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    CancerNews posted an update

    Cancer Patients at Special Risk for COVID-19?
    — Retrospective data from Wuhan point to the possibility
    by Ian Ingram, Deputy Managing Editor, MedPage Today March 26, 2020

    Cancer patients receiving care at a single center in Wuhan, China, were twice as likely to be diagnosed with COVID-19 as the general population, according to researchers there.

    Among more than 1,500 patients admitted to a tertiary cancer hospital in the early part of the year, 0.79% were ultimately diagnosed with the COVID-19 coronavirus (SARS-CoV-2), as compared with an infection rate of 0.37% in the city overall (OR 2.31, 95% CI 1.89-3.02), reported Conghua Xie, MD, of Zhongnan Hospital of Wuhan University, and colleagues.

    The results, published in JAMA Oncology, support those from another single-center study suggesting that hospital-acquired infections were a likely source of spread in Wuhan. Cancer patients are thought to be at higher risk of contracting COVID-19, as they typically require repeat visits for care, and often receive immunosuppressive treatments such as chemotherapy or radiation.

    In the study, lung cancer patients appeared to be at particular risk. Among 228 non-small cell lung cancer patients, seven (3%) were diagnosed with COVID-19 pneumonia (1.8% in those 60 or younger and 4.3% in those over 60).

    "Our findings imply that hospital admission and recurrent hospital visits are potential risk factors for SARS-CoV-2 infection," the group wrote. "We propose that aggressive measures be undertaken to reduce frequency of hospital visits of patients with cancer during a viral epidemic going forward."

    In the wake of the COVID-19 pandemic, U.S. cancer centers are already establishing protocols to address the changing landscape of patient management. During a webinar hosted by Oncology Business Review on Monday, Debra Patt, MD, MPH, MBA, of Texas Oncology in Austin, discussed some of the strategies at her clinic aimed at reducing the risk of infection.

    To preserve clinic safety for patients on active treatment, infusion chairs were placed 6 feet apart, visitors were minimized, and all routine follow-up visits were pushed back.

    "I decreased my clinic volume by about 70%," she said. "We don't want to have a packed waiting room, or a packed infusion center right now."

    Treatments deemed unlikely to adversely impact outcomes were also considered for delay (e.g., zoledronic acid for bone health), and Patt said that the risks and benefits of all interventions should be assessed before proceeding.

    "By and large, cancer does need treatment, and most of that needs to be treated in a timely way, but there are things that one can forego," she said.

    Describing a hypothetical case involving a BRCA-positive triple-negative breast cancer patient who elected bilateral mastectomy and reconstruction, and needs immediate surgery, Patt suggested a staged procedure, delaying reconstruction until a later time to minimize the patient's in-hospital time and decrease her risk for exposure to the virus.

    She also highlighted the switch to telehealth for routine visits and especially for the management of potentially infectious patients.

    "If they have an acute symptom, I really don't want to bring that patient into clinic," she said. "And I don't want to send them to the emergency room, because if I routinely send patients with acute complaints to the emergency room, I would be sending them to the highest concentration of COVID-19 in the city."

    In the study from Xie and colleagues, 12 of the 1,524 patients at the single center in Wuhan were diagnosed with the COVID-19 coronavirus from Dec. 30, 2019 to Feb. 17, 2020. Across the entire city during this time, there were 41,152 cases out of 11 million individuals.

    Median patient age of the cancer patients diagnosed with COVID-19 was 66 years (range 48-78), two-thirds of whom were over 60. Three of the 12 patients developed severe adult respiratory syndrome. By March 10, three of the patients had died, three remained in hospital, and six had been discharged.


    The study was funded in part by a National Medical Research Council Clinician-Scientist Award.

    Xie and co-authors disclosed no relevant relationships with industry.

    The Oncology Business Review webinar was sponsored by GlaxoSmithKline.

    Primary Source

    JAMA Oncology

    Source Reference: Yu J, et al "SARS-CoV-2 transmission in patients with cancer at a tertiary care hospital in Wuhan, China" JAMA Oncol 2020; DOI: 10.1001/jamaoncol.2020.0980.

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    CancerNews posted an update

    What Cancer Survivors Need After Treatment Concludes

    Surviving cancer can bring its own set of challenges. When the appointments and treatments and medications end, rural cancer survivors especially can feel set adrift, and sometimes suffer from what comes after the drama and frenzy of illness: cancer’s physical toll, as well as anxiety, depression, difficulty with work, finances, and relationships.

    It’s a critical stage, said University of Virginia School of Nursing associate professor Pam DeGuzman, who over the past three years has developed, implemented and studied the effects of a nurse-led intervention for cancer survivors to gauge their psycho-social health and wellness weeks and months after their treatments have ended.

    DeGuzman, who earned a National Cancer Institute grant administered by UVA’s Cancer Control and Population Health program, said the power of the telehealth intervention belies its simplicity. Even a 20-minute online chat can make a difference, she said.

    Q. For people who’ve survived cancer, why is the post-treatment stage so critical?

    A. Imagine you’re in a rural area, maybe five or six hours away from the hospital, and you don’t come back for treatment anymore. You lose that connection. When you do come back in for a follow-up, it’s very medically focused. And while that’s important, it doesn’t necessarily leave room for what we call cancer-related distress.

    Say you’re having difficulty sleeping or feeling fatigued, or maybe you’re having trouble with your spouse, or can’t pay your bills, or are having trouble getting back to work – it could be a whole range of psycho-social things. You might not even think of the cancer center as a place to get help.

    We already try to prepare people for this time by giving them information about how to care for themselves once treatment is over. But when we check with survivors later and ask them what they remember about what we told them, we hear, “Oh, that pile of papers.” No one’s looking at these documents, especially because we give [the information] to them right when treatment ends. At that point, all they’re thinking about is, “I’m done with treatment. I lived; I’m good.” But sometimes, they’re not.

    Q. What does your intervention look like, and who is it for?

    A. I developed a nurse-led telemedicine cancer survivorship intervention that’s done over a video conference call – sort of like Skype or Facetime, but private, and HIPPA-secure, the technology that we get from UVA’s Rheuban Center for Telehealth. The population we tested the intervention with are survivors of head and neck cancers. We worked closely with our co-investigator, UVA surgeon Dr. Mark Jameson, to launch the intervention. We have a fantastic UVA Cancer Center nurse, Allen Cupp, who calls patients about six weeks after they finish their active treatment.

    Allen’s protocol includes taking patients through questions on a distress thermometer: about 20 questions on general things like whether they’re having family issues, dealing with financial difficulties or having transportation or child care problems, and then a group of questions specific to their recovery: fatigue, jaw-swelling, swallowing, difficulty speaking. The distress scale is one to 10, and measures distress experienced over the last four weeks. For anything that ranks over a five, Allen does some counseling, some education, and offers referrals.

    The thing about the distress thermometer is that it brings up all these things you wouldn’t otherwise be asking about. On average, the whole thing takes 15 to 20 minutes.

    Q. Why choose head and neck cancer survivors as your first population to test?

    A. It’s not a very common cancer – about 50,000 Americans get it every year – but this group is quite vulnerable. If you can imagine having cancer on your head or neck, many treatments you get for this kind of cancer – often radiation and surgery – are visible to all the world. People who deal with other cancers – prostate, breast, and so on – have more options if they want to hide what’s happening; it’s less public. With head and neck cancer, though, you probably cannot hide it. Your facial integrity may have changed. These patients can have problems with their speech, with drooling, swallowing. Some end up having assistive voice technologies. Because of [all this], depression and anxiety are really high among this group.

    They also have the second-highest suicide rate among all populations with cancer: three to four times the rate of the general population. UVA’s Cancer Center has resources to help them, but we also know that cancer survivors are less likely to travel long distances for non-treatment care. We need another way to make this connection.

    Q. Why do the video conference? Why not just a phone call?

    A. It’s important to be able to visually assess the patient, so face-to-face is key. These people have often just had surgery, so the nurse does a physical assessment during the call. Also, because part of the assessment is related to people’s effect – how they seem to be doing – it’s critical to have a clear visual on them, just as you would if they were in a room together. And third, patients say they really like it.

    Q. Internet service in rural areas can be dicey. Did you face any tech issues?

    A. I did. In many of Virginia’s rural communities, fewer than 25% of residents have broadband access, according to U.S. Census-tract maps I’ve created. In our ideal situation, people would have fixed broadband and a video camera, but that’s often not the case.

    We’re currently evaluating public libraries to see if they are feasible telemedicine sites; most are within a 30-minute drive of nearly every Virginia resident, no matter where they live. With that, then, all that our participants without broadband would need is a private space in a library, an iPad, or a computer with a camera.

    Equally difficult to the issue of rural connectivity, though, is the issue of digital inclusion. Just because you have a smartphone doesn’t mean you can successfully get a telemedicine call. Some of it has to do with technological savvy.

    Q. How was the intervention received? What did patients tell you?

    A. People love it. We’ve put 20 patients through the intervention, and preliminary data show it’s successful. The nurse is making a lot of referrals, and people are following up on those referrals, which means patients are getting connected to the kind of help they need. That’s a positive sign.

    Also, we’ve seen that this may be a culturally acceptable way to get mental health resources to rural people who need them. In many areas, there can be a stigma attached to getting psycho-social help; we think that may have something to do with rural self-reliance. But our qualitative data show that patients are using the visit with the nurse as their counseling. This isn’t a visit with a therapist or social worker; it’s a visit with a nurse, and we think that’s perceived as a different, perhaps more acceptable, kind of help.

    Q. What’s next?

    A. We’re currently looking at the quality of life issues – how people feel physically, how their relationships are, whether they have physical pain, anxiety, depression and so on. And so far, people who receive the intervention are showing improvement. I’m writing a grant and hoping to scale this up, and broaden it to include lung cancer survivors, too, with a protocol that’s completely customized. Their rate of suicide is the highest of all cancer survivors – six times the rate of the general population. So this gives us a way to figure out what’s happening, and what’s needed.

    There is also new legislation written into Medicare that says the government will reimburse for telehealth support – $42 a visit – if the person is over age 65 and has had cancer as well as another chronic illness, like diabetes or arthritis. We think it will prove to be cost-effective, too, being mostly the cost of the nurse; the equipment and other incremental costs are negligible.

    This gives us a way to support patients beyond cancer with a new structure and protocol. So far, it’s really helping people; maybe saving them from having to come back to the hospital – or actually making them better. It’s also really just the right thing to do.

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    CancerNews posted an update

    By Nancy Badertscher, For the AJC

    Roswell artist Bivi Franco has devoted nearly 10 years to trying to lift the spirits of cancer patients with handmade jewelry and other artistry.

    “I’m not a doctor. I’m not someone who can cure cancer,” said Franco, founder and director of the nonprofit Feel Beautiful Today (www.feelbeautifultoday.org). “But I felt I needed to be love-in-action and do something.”Franco and a team of 10 volunteers – many cancer survivors themselves – are regularly in infusion and radiation centers across metro Atlanta, providing love, support and a welcome distraction to cancer patients.
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    To date, about 10,130 metro Atlantans have benefited from nine programs Franco has created that are free to cancer patients and survivors and that play to her passion for art.In one program, volunteers bring high-end supplies into hospitals and help patients create keepsake bracelets of precious stones, crystals, and fresh pearls while they’re waiting for or receiving treatments. All the programs — including those involving mixed media and photography — are funded through donations and focus on uplifting the patients by helping them see the beauty in art and in themselves.

    inRead invented by Teads
    “What we do allows patients to have some beautiful time – some meaningful time – away from the concept of cancer,” Franco said. “At least for a little while, they forget about feeling sick or how anxious they are.”Northside is one of 13 hospitals in metro Atlanta that has opened its doors to Franco’s program for several years.“It’s a phenomenal program,” said Kymberly Duncan, survivorship coordinator at Northside Hospital Cancer Institute.

    The bracelets that the patients make and keep “are usually a pick-me-up if a patient is having a bad day or they just started treatment,” she said. “It’s just kind of something extra to boost their spirits.”Breast cancer survivor Mona Fletcher met Franco six years ago when Franco was hosting a survivors’ workshop at Camp Hope.“Bivi touches a lot of cancer survivors’ lives,” said Fletcher, who has participated in Feel Beautiful Today programs, including the quarterly workshops held at Nordstrom at Perimeter Mall. “Her calming and caring demeanor is therapeutic.”Lisa Walters, 47, of Canton, said she met nine brave cancer patients and survivors whom she now calls friends at one of Franco’s arts and crafts workshops.“Those who have not gone through cancer don’t understand what we’ve been through, though they try,” said Walters, whose 2017 breast cancer diagnosis required three surgeries, six rounds of chemo and 11 rounds of immunotherapy. “Life after cancer is quite an adjustment, a roller coaster ride, but having this group of women who really do get what you’re feeling is amazing.”Walters, Fletcher, and other cancer survivors have been part of “The Warrior Within,” a narrative photo exhibit that Franco created that has been on display at local hospitals and has been made into a book.The exhibit is meant to “create an awareness that this patient is not only a cancer patient but a human being like you and me,” Franco said.Some of “The Warrior Within” models also appear in an annual fashion show that is the nonprofit’s big fundraiser.A professional artist and designer, Franco said she was inspired to create the nonprofit after an aunt and two close friends were diagnosed with cancer. Only one of the friends survived. The mission became even more personal in 2015 when her mother was diagnosed with a rare form of cancer, Franco said.She said her goal is to remind cancer patients that no matter how the disease ravages the body, the spirit is forever beautiful.“Cancer may affect the physical being. But the beauty within will continue to glow with hope,” Franco said.

    “Since I was a child I realized that art was going to be part of my life. At a very early age, I began to paint, draw, design and create all types of projects which led me to my degree in design.”

    When did you decide that you wanted to put your artistic/design talents to helping cancer patients?

    “Seeing the pain and struggles of my aunt and two friends battling cancer I was moved to make a difference by giving them hope through something beautiful.”

    What’s the most rewarding about doing this?

    “Perhaps the most rewarding part of FBT is getting to witness the change in the patient’s demeanor. Some come into our workshops with a lot of pain and anxiety because of their treatments. Then, at the end of the workshop, their attitude has changed drastically. They begin to smile, to laugh, to share with others and for a moment their pain is gone. Their sense of satisfaction is incredible, along with their tears of joy and hugs and thank yous.”

    How can readers help?

    “For 2020, our goal is to provide another 1,500 cancer patients with our programs free of charge. In order to make that happen, we need more volunteers and donations.”


    We recognize a big part of our journalistic mission is to shine a spotlight on wrongdoings and to hold our public officials accountable.

    But we also understand the importance of celebrating our region’s moments, milestones and people. That’s exactly what we hope to accomplish with Inspire Atlanta.

    Each week, Inspire Atlanta will profile a person that makes metro Atlanta a better place in which to live.

    Of course, we can’t do this alone: We need your help in finding extraordinary people and identifying inspiring stories across our region. We learned about Bivi Franco from fellow artist Pat Fiorello of Sandy Springs.

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    CancerNews posted an update

    Study examines causes of death in US breast cancer survivors

    Survival rates for patients with breast cancer have improved significantly in the last four decades, and many patients will eventually die from non-cancer-related causes. Researchers recently conducted the largest population-based long-term retrospective analysis of non-cancer causes of death among patients with breast cancer. The findings are published early online in CANCER, a peer-reviewed journal of the American Cancer Society.

    Of 754,270 U.S. women diagnosed with breast cancer from 2000 to 2015, 24.3 percent died by the end of 2015. The highest number of deaths (46.2 percent) occurred within one to five years following diagnosis, and most were caused by breast cancer or other cancers. Breast cancer-related deaths decreased as years passed, however, and were eventually overcome by non-breast cancer causes of death. Within five to 10 years following diagnosis, about half of patients died of non-breast cancer causes, whereas the majority of those who survived beyond 10 years died of non-breast cancer causes.

    The most common non-cancer causes of death within 10 years of diagnosis were heart diseases, followed by cerebrovascular diseases. After more than 10 years following diagnosis, the most common non-cancer causes of death were heart diseases, followed by Alzheimer's disease.

    Compared with the general population, patients had a higher risk of dying from chronic liver diseases within 5-10 years following diagnosis, and from Alzheimer's disease and heart diseases after more than 10 years following diagnosis.

    "Non-cancer diseases, such as heart diseases, contribute to a significant number of deaths in patients with breast cancer, even higher than in the general population," said senior author Mohamad Bassam Sonbol, MD, of Mayo Clinic in Phoenix, Arizona. "Cancers other than breast cancer are also an important cause of death in patients with a history of breast cancer."

    The results will be informative for survivors in discussions with physicians about their future health. "Our findings emphasize the importance of counseling patients about their survivorship and risk of developing other cancers, with a focus on proper screening or preventive measures for other cancers and diseases," added Dr. Sonbol.


    Additional Information

    NOTE: The information contained in this release is protected by copyright. Please include journal attribution in all coverage. A free abstract of this article will be available via the Cancer News Room upon online publication. For more information or to obtain a PDF of any study, please contact:

    Penny Smith +44 (0)[phone number redacted]48 (UK)
    [email redacted]
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    CancerNews posted an update

    Originally published in HemOnc Today or Healio.com/HemOnc | Date TBD, 2017
    n this supplement to HemOnc Today, we have
    compiled the most-read articles written about ovarian
    cancer this year.
    From risk reducing measures (below) to improving
    progression-free survival (pages 12 and 14), our experts
    researched and weighed in on the spectrum of this
    deadly carcinoma.
    “These are exciting times in ovarian cancer research
    and, more importantly, for patients. Recent discoveries
    have realized the possibility that this is the beginning
    of the end of ovarian cancer,” Michael J. Birrer, MD,
    PhD, writes in his editorial (page 10). “Our new
    understanding of the origins of this disease may give
    rise to a reasonably effective early detection assay, which
    remains the holy grail of ovarian cancer research.”
    To follow along this journey, be sure to follow
    @HemOncToday on Twitter and visit Healio.com
    The Editors of HemOnc Today
    © Copyright 2019, Healio. All rights reserved. No part of this publication may be reproduced without written permission. The ideas and opinions expressed in this HemOnc Today® supplement do not necessarily
    reflect those of the editor, the editorial board or the publisher, and in no way imply endorsement by the editor, the editorial board or the publisher.
    6900 Grove Road, Thorofare, NJ 08086 USA • phone:[phone number redacted] • Healio.com/HemOnc
    This HemOnc Today supplement is produced by Healio.
    Delivering the best in health
    care information and
    education worldwide
    Take a look back at the top
    ovarian cancer news from 2019
    Originally published in HemOnc Today | November 25, 2019
    Oral contraception reduces risk for
    aggressive ovarian cancer
    Oral contraceptive use reduced
    risk for fatal aggressive ovarian cancer, with a greater risk
    reduction observed with longer birth
    control use, according to study results.
    Although it has been known that
    oral contraceptive use reduces the risk
    for ovarian cancer, this is the first study
    to show the risk reduction is driven
    by a lower incidence of aggressive and
    highly fatal subtypes of ovarian cancer.
    “The longer the history of oral
    contraceptive use, the greater the
    protection,” Jennifer M. Mongiovi,
    cancer epidemiology fellow in the
    department of epidemiology and
    environmental health at University at
    Buffalo, said in a press release. “For
    every 5 years of use, we observed 32%
    lower odds of highly fatal disease,
    compared to 13% for all ovarian
    cancer as previously reported by other
    researchers. This association also
    varies by histological subtype, and was
    found most protective for highly fatal
    endometrioid ovarian cancers.”
    Mongiovi and colleagues evaluated
    data from 20 case-control studies
    in the Ovarian Cancer Association
    Consortium. The analysis included 579
    women who died within 12 months of
    their diagnosis, matched 1:4 by 5-year
    age categories, race and study site to
    2,279 controls, as well as 1,294 patients
    who died within 18 months matched
    to 5,095 controls.
    Analyses adjusted for age, site and
    parity showed any oral contraceptive
    use was associated with a 46%
    reduction in the odds of death within
    12 months (OR = 0.54; 95% CI, 0.43-
    Researchers conducted separate
    models for duration of oral
    contraceptive use per 5-year increase.
    Results showed a 66% reduction in odds
    of death within 12 months for those
    who used oral contraceptives for more
    than 10 years (OR = 0.34; 95% CI, 0.23-
    0.49), whereas there was no significant
    risk reduction for those who used
    oral contraceptives for 1 year or less
    (OR = 0.83; 95% CI, 0.6-1.14).
    These trends were consistent
    among women who died within 18
    months; however, oral contraceptive
    use appeared more protective among
    highly fatal cases, or those who died
    within 12 months.
    Use of oral contraception appeared
    most protective for endometrioid
    subtypes among those who died within
    12 months (OR = 0.43, 95% CI, 0.2-
    0.93) and 18 months (OR = 0.39, 95%
    CI, 0.23-0.65).– by Alexandra Todak n
    Mongiovi JM, et al. Abstract 641/25. Presented
    at: AACR Annual Meeting; March 29-April 3,
    2019; Atlanta.
    Disclosures: The authors report no relevant
    financial disclosures.
    to read the full article and
    perspective online at
    3 | December 10, 2019 | Healio.com/HemOnc
    Originally published on Healio.com/HemOnc | July 26, 2019
    Niraparib induces responses in late-line,
    BRCA-negative ovarian cancer
    Niraparib demonstrated clinically relevant activity among
    women with heavily pretreated
    ovarian cancer, particularly those with
    homologous recombination deficiencypositive, platinum-sensitive disease,
    according to findings from the phase
    2 QUADRA study published in The
    Lancet Oncology.
    The results, which also showed no
    new safety signals, support extending the use of poly(ADP-ribose) polymerase (PARP) inhibitors to a wider
    population of women with late-line
    ovarian cancer, including those without
    BRCA mutations.
    “This is another piece of the puzzle
    that helps our patients live longer,”
    Kathleen Moore, MD, associate director of clinical research at Stephenson
    Cancer Center
    at University of
    Oklahoma College of Medicine,
    said in a press
    release. “There
    haven’t been a lot
    of studies done
    on patients without BRCA mutations who have
    received four, five, six or more lines
    of chemotherapy. That’s who this trial
    sought to study.”
    As many as 25% of women without
    a BRCA mutation can develop homologous recombination deficiency (HRD),
    which means they can derive benefits
    from PARP inhibitors such as niraparib
    (Zejula, Tesaro).
    In the multicenter, open-label, single-arm, phase 2 study, Moore and colleagues enrolled 463 women aged 18
    years and older (median age, 65 years;
    range, 29-91) with metastatic, relapsed,
    high-grade serous (grade 2 or 3) epithelial ovarian, fallopian tube or primary
    peritoneal cancer who had undergone
    at least three prior chemotherapy regimens. Patients had ECOG performance
    status of 0 or 1 and adequate organ
    function and had received a median
    four (interquartile range [IQR], 3-5)
    previous lines of treatment.
    The study was conducted at 56 sites
    in the United States and Canada.
    Women received 300 mg oral niraparib once daily starting on day 1 and
    continuously through each 28-day cycle
    until disease progression, unacceptable toxicity or withdrawal of consent.
    The prevalence of confirmed overall
    response among women with HRDpositive tumors — including those
    with and without BRCA mutations
    — who showed sensitivity to their last
    platinum-based therapy served as the
    study’s primary objective.
    Median follow-up for OS was 12.2
    months (IQR, 3.7-22.1).
    Among all women who initiated
    treatment, 151 (33%) had platinumresistant disease and 161 (35%) had
    platinum-refractory disease.
    Results showed 13 of 47 women
    with platinum-sensitive, HRD-positive
    tumors naive to PARP inhibitors demonstrated overall response (27.65%;
    95% CI, 15.6-42.6). These women had
    median PFS of 5.5 months (95% CI,
    3.5-8.2) and median duration of response of 9.2 months (95% CI, 5.9 to
    not estimable), and 68% (95% CI, 53-
    81) achieved disease control.
    “We don’t normally see response
    rates of more than 10% in women who
    have had four, five and six chemotherapy treatments,” Moore said in the press
    release. “So, a 27% response, especially
    given that these were not all women
    with BRCA mutations, was a nice signal
    that these patients can still benefit from
    PARP inhibitor use.”
    Median OS was 26 months (95% CI,
    18.1 to not estimable) among women
    with BRCA mutations, 19 months (95%
    CI, 14.5-24.6) among women with
    HRD-positive tumors and 15.5 months
    (95% CI, 11.6-19) among women with
    HRD-negative tumors.
    The most prevalent drug-associated
    grade 3 or worse adverse events included anemia (24%) and thrombocytopenia (21%). Researchers observed serious treatment-emergent adverse events
    in 43% of all women, including small
    intestine obstruction (7%), thrombocytopenia (7%) and vomiting (6%). One
    treatment-related death occurred due
    to gastric hemorrhage.
    The researchers reported several
    limitations to their study, including its
    single-arm, nonrandomized design. Although the study was powered for the
    primary outcome, it was not powered
    for analyses of subgroups.
    “We think [these data support] the
    expansion of niraparib to be more inclusive of patients. PARP inhibitors
    work best in women with BRCA mutations, but they can still work well in
    women without the mutation,” Moore
    said in the release. “Niraparib really
    makes sense for a much broader population.” – by Jennifer Byrne n
    Moore KN, et al. Lancet Oncol. 2019;
    Disclosures: Moore reports honoraria or advisory board fees from AstraZeneca, Clovis
    Technology, Genentech, ImmunoGen, Janssen, Roche, Tesaro and VBL Therapeutics.
    Please see the study for all other authors’ relevant financial disclosures.
    Kathleen Moore
    “Niraparib really makes
    sense for a much broader
    Kathleen Moore, MD
    4 | December 10, 2019 | Healio.com/HemOnc
    Originally published in HemOnc Today | August 10, 2019
    Ovarian cancer: Is this the beginning
    of the end?
    by Michael J. Birrer, MD, PhD
    here will be 22,530 new cases of
    ovarian cancer in the United States
    this year.
    Although tumors often present at an
    advanced stage, it remains one of the
    most chemosensitive epithelial cancers,
    with a response rate of 70% to 80% after
    initial surgery and chemotherapy.
    Unfortunately, most patients relapse
    and develop chemotherapy-resistant
    disease. Approximately 14,000 U.S.
    women will die this year of ovarian
    cancer. No gynecologic malignancy has
    a higher fatality rate.
    Despite decades of research into the
    pathogenesis and molecular origins of
    ovarian cancer, progress has been quite
    slow. Carboplatin and paclitaxel have
    been the standard therapy for more
    than 15 years.
    However, in the last decade, there
    has been a revolution in our understanding of the origin of this tumor and
    its important molecular pathways. This
    has led to the development of novel effective therapies and, ultimately, better
    clinical management of the disease.
    These advances have generated optimism that we may begin to see more
    women cured of this disease, or effectively managed so they can live long,
    comfortable lives.
    The major new discoveries that contributed to this optimism include the
    recognition of the fallopian tube as a
    source for many ovarian cancers; largescale systematic molecular analysis of
    high-grade serous ovarian cancers; and
    the development, testing and FDA approval of new agents, such as bevacizumab (Avastin, Genentech) and PARP
    Ovarian cancer is not ovarian
    One of the conundrums in ovarian
    cancer research for many years was the
    lack of validated preneoplastic lesions
    for this tumor.
    The discovery and understanding of
    BRCA1/BRCA2 mutations as the basis
    of breast-ovary syndrome established
    a group of women at high risk for this
    Prophylactic removal of these patients’ ovaries and tubes allowed for the
    first time a systematic examination of
    pathologic specimens from high-risk
    patients. Even then, the identification
    of preneoplastic lesions on the ovarian
    surface was difficult to establish.
    When several laboratories and pathologists began to examine the fallopian tubes, it became clear these patients harbored preneoplastic lesions in
    the surface epithelium of the fallopian
    tubes, with most located toward the distal end near the fimbria.
    These lesions — called serous tubal
    intraepithelial carcinomas — have been
    found in a significant number of prophylactically removed specimens, and
    there is a general consensus that these
    are preneoplastic lesions for high-grade
    serous tumors.
    Other abnormalities in the tubes,
    such as p53 signatures — clonal expansions of normal-appearing epithelial
    cells that stain for TP53 — remain to be
    defined. However, this work radically
    changed the field of ovarian cancer research.
    It provided a source of new, important tissue, which can be used to examine the early events in tumor development, along with potential genomic and
    protein markers that may be valuable
    for early detection. Further, it raised
    the issue of removing the fallopian tube
    alone a risk-reducing procedure.
    Molecular analysis
    The work of many laboratories over
    the past 10 years has provided a molecular underpinning for the observation of pathologists and surgeons that
    ovarian tumors of different histologies
    have unique clinical and anatomic differences.
    Molecular analysis demonstrated
    that high-grade serous ovarian cancers
    are the result of genomic chaos with a
    major defect in DNA repair; clear cell
    cancers result at least, in part, from inactivation of ARID1A, a gene involved
    in chromatin structure; mucinous tumors of the ovary behave much like
    their gastrointestinal counterpart and
    likely are the result of aberrant RAS/
    RAF signaling; and endometrioid
    cancers behave like their endometrial
    counterparts with abnormalities in the
    PI3K pathway.
    These molecular differences reinforced that these tumors are unique
    diseases and require separate clinical
    “Despite decades of research into the
    pathogenesis and molecular origins of
    ovarian cancer, progress has been
    quite slow.”
    Michael J. Birrer, MD, PhD
    5 | December 10, 2019 | Healio.com/HemOnc
    The Cancer Genome Atlas study —
    a large-scale, NCI-driven consortium
    project — examined the genomic features of high-grade serous ovarian cancer on multiple platforms. Although the
    results reinforced many of the previously known genomic aspects of this tumor,
    this study provided a launching point
    for many new hypotheses and potential
    treatment algorithms.
    A high-grade ovarian serous cancer
    results from a severe defect in DNA repair. This results, at least in part, from
    mutations in p53 and in BRCA1/BRCA2
    or one of the other genes within the
    Fanconi DNA repair pathway. This produces a homologous recombination deficiency that creates an inability to repair
    DNA double-stranded breaks.
    As a result of this abnormality, the tumor has very few high-frequency mutational events outside of p53 or BRCA1/
    BRCA2. This tumor cannot be targeted
    effectively by small molecule inhibitors
    like those used for melanoma and lung
    The abnormality in homologous recombination deficiency results instead
    in the shift of large amounts of DNA,
    producing amplifications in the lesions
    throughout the genome. The precise
    genes that drive the tumor remain to be
    In addition, the genomic plasticity
    of high-grade serous ovarian cancer has
    raised issues of the degree of heterogeneity that exists within tumor diagnosis
    and its evolution under the pressure of
    therapeutic intervention.
    New therapies
    After little progress in the development of new ovarian cancer therapies in
    the 1990s and early 2000s, a better understanding of the activated molecular
    pathways led to 10 new indications in
    the past 5 years.
    Early work on the microenvironment of ovarian cancer tumors suggested this tumor was, in part, a VEGFdriven tumor.
    The use of bevacizumab for ovarian
    cancer is well-established now. It is used
    primarily for recurrent disease but, with
    time, may migrate more toward upfront
    The discovery and characterization
    of high-grade serous ovarian cancer as a
    disease of genomic instability prompted
    scientists to question whether this is targetable.
    Early work began to focus on the
    PARP protein as being heavily involved
    in the repair of single-stranded breaks.
    Inhibition of single-stranded breaks will
    lead to double-stranded breaks, which
    cannot be repaired unless homologous
    recombination is intact. It was a wonderful example of bench-to-bedside efforts
    that led individuals to hypothesize that
    inhibition of the PARP protein should
    be particularly effective for tumors with
    BRCA1 or BRCA2 mutations.
    The early laboratory data supported
    this hypothesis of synthetic lethality
    with a number of seminal publications
    in high-impact journals. This led to a
    relatively rapid translation of this concept into early drug development and,
    ultimately, to randomized phase 3 trials.
    These trials have been an astonishing leap forward in that the laboratoryobserved synthetic lethality could be
    demonstrated in patients.
    The initial approvals for this class of
    drugs in the United States were based on
    treatment and response rates.
    Subsequent randomized, doubleblind, placebo-controlled trials evaluated PARP inhibitor maintenance therapy for patients with high-grade serous
    ovarian cancer that had responded to a
    platinum regimen.
    Three trials that evaluated women
    with platinum-sensitive recurrent disease — NOVA, SOLO2 and ARIEL3
    — were strongly in favor of PARP inhibition. Of note, the NOVA trial treated
    all comers, and even those patients
    who had wild-type BRCA1/BRCA2 and
    scored normal in homologous recombination deficiency assays benefited from
    PARP inhibition.
    The results of the SOLO-1 trial demonstrated that, for patients with germline or somatic BRCA1 or BRCA2 mutations, maintenance in the frontline is
    very effective. Use of PARP inhibitors
    in ovarian cancer has now moved up to
    maintenance in frontline therapy.
    These agents have been extremely
    well-tolerated, with some class effects of
    nausea and fatigue that usually are reasonably well-controlled.
    These are exciting times in ovarian
    cancer research and, more importantly,
    for patients. Recent discoveries have realized the possibility that this is the beginning of the end of ovarian cancer.
    Our new understanding of the origins of this disease may give rise to a reasonably effective early detection assay,
    which remains the holy grail of ovarian
    cancer research.
    The molecular analysis of ovarian
    cancers with different histologies will
    allow us to begin to stratify patients appropriately to maximize efficacy and
    minimize toxicity.
    The emergence of new, effective
    agents, such as antiangiogenics and
    PARP inhibitors, has brought on the
    dawn of a new era for ovarian cancer —
    one in which it is conceivable to begin
    to whisper about the possibility of curing patients or, at the very least, better
    managing their disease so as to convert
    a lethal disease into a chronic one. n
    See references online at Healio.com/HemOnc.
    For more information:
    Michael J. Birrer, MD, PhD, is professor of medicine, OB/GYN and pathology in the division of
    hematology/oncology at The University of Alabama at Birmingham. He can be reached at [email redacted].
    Disclosure: Birrer reports consultant/advisory
    roles with AstraZeneca, Bristol-Myers Squibb,
    Clovis Oncology, EMD Serono, F. Hoffmann-La
    Roche, Genentech, Merck Sharp & Dohme, Pfizer
    and Tesaro.
    6 | December 10, 2019 | Healio.com/HemOnc
    Originally published in HemOnc Today | November 25, 2019
    Adding olaparib to maintenance bevacizumab
    improves PFS in ovarian cancer
    he addition of olaparib to bevacizumab maintenance therapy after
    first-line platinum-based chemotherapy and bevacizumab significantly
    improved PFS among women with
    advanced ovarian cancer, according
    to results of the randomized phase 3
    PAOLA-1/ENGOT-ov25 study.
    The PFS benefit appeared particularly substantial among women with
    BRCA mutations and those with homologous recombination deficiencypositive disease, researchers noted.
    However, the benefit is sufficient to
    support use of this regimen as a standard of care in this setting regardless
    of BRCA mutation status, Isabelle L.
    Ray-Coquard, MD, PhD, medical oncologist in the medical oncology department and Institute for Clinical Science at Centre Leon Berard in France
    and professor of medical oncology at
    University Claude Bernard Lyon I, told
    HemOnc Today.
    “It also confirms the importance of
    bevacizumab in the treatment of ovarian cancer patients in the first-line setting],” Ray-Coquard said.
    PAOLA-1/ENGOT-ov25 was the
    first phase 3 trial designed to evaluate
    the safety and efficacy of a PARP inhibitor in combination with bevacizumab (Avastin, Genentech) as first-line
    maintenance therapy for women with
    advanced ovarian cancer regardless of
    BRCA1 or BRCA2 mutation status.
    The study included 806 women with
    stage III or stage IV high-grade serous
    or endometrioid ovarian, fallopian tube
    or primary peritoneal cancer who were
    in clinical complete or partial response
    after receiving standard platinumbased chemotherapy in combination
    with bevacizumab.
    Researchers randomly assigned
    the women 2:1 to maintenance bevacizumab with the poly(ADP-ribose)
    polymerase (PARP) inhibitor olaparib
    (Lynparza, AstraZeneca; n = 537) or
    with placebo (n = 269).
    Researchers administered olaparib
    at 300 mg orally for up to 24 months
    and bevacizumab at 15 mg/kg for 15
    PFS in the intent-to-treat population
    served as the study’s primary endpoint.
    Median follow-up was 24 months in
    the olaparib group and 22.7 months in
    the placebo group.
    Results showed significantly longer median PFS in the olaparib group
    compared with the placebo group (22.1
    months vs. 16.6 months; HR = 0.59;
    95% CI, 0.49-0.72).
    Among patients with BRCAmutated tumors, median PFS was
    37.2 months in the olaparib group
    vs. 21.7 months in the placebo group
    (HR = 0.31; 95% CI, 0.2-0.47). Among
    women without BRCA mutations, median PFS was 18.9 months in the olaparib
    group vs. 16 months in the placebo group
    (HR = 0.71; 95% CI, 0.58-0.88).
    Women with homologous recombination deficiency (HRD)-positive
    disease had median PFS of 37.2 months
    with olaparib vs. 17.7 months with placebo (HR = 0.33; 95% CI, 0.25-0.45).
    Women with HRD-positive status without BRCA mutations had median PFS
    of 28.1 months with olaparib and 16.6
    months with placebo group. Women
    with HRD-negative or unknown status
    had median PFS of 16.9 months with
    olaparib and 16 months with placebo.
    “It is interesting to note that PFS
    in the combination arm is longer than
    what was seen in the SOLO-1 trial,
    which is probably due to the use of
    bevacizumab,” Ray-Coquard said.
    Ovarian cancer is the eighth most common cancer in the
    world, with 295,000 women being diagnosed and over
    185,000 deaths each year. The majority of women relapse, with
    the 5-year survival being 20% for stage III disease and 5% for
    stage IV disease.
    PARP inhibitors have revolutionized the treatment landscape
    of ovarian cancer. Olaparib, niraparib (Zejula, Tesaro/GlaxoSmithKline) and rucaparib (Rubraca, Clovis Oncology) are
    approved for recurrent ovarian cancer and have shown to increase PFS. But if we are really going to have a chance to improve OS and get more
    women cured, we are going to have to bring these drugs into the first-line setting.
    Susana Banerjee, PhD, MA, MBBS, FRCP
    The Royal Marsden Hospital
    Disclosure: Banerjee reports honoraria and consultant roles with AstraZeneca, Clovis Oncology and
    GamaMabs; honoraria from Immunogen, Merck and Roche; a consultant role with Seattle Genetics; and
    travel expenses from Nucana.
    Susana Banerjee
    to read the full perspective
    from Banerjee or by searching the
    headline online at Healio.com/HemOnc.
    Adding continues on next page
    7 | December 10, 2019 | Healio.com/HemOnc
    Grade 3 or higher adverse events
    occurred among 57% of women in
    the olaparib group and 51% of patients in the placebo group. More
    than half of the women in the olaparib group (54%) had dose interruptions because of adverse events,
    compared with 24% in the placebo
    “[This study] population is representative of the majority of patients with advanced ovarian cancer [because] patient selection was
    not restricted by surgical outcome
    or BRCA mutation status,” RayCoquard said during a press conference. “I can also tell you that the
    safety profile of olaparib in combination with bevacizumab was generally consistent with previous trials and the addition of olaparib did
    not have an impact on bevacizumab
    tolerability and quality-of-life.”
    – by John DeRosier n
    Ray-Coquard IL, et al. Abstract LBA2_PR.
    Presented at: European Society for Medical
    Oncology Congress; Sept. 27-Oct. 1, 2019;
    Barcelona, Spain.
    Disclosures: Arcagy, AstraZeneca and
    Roche funded this study. Ray-Coquard
    reports consultant roles with and honoraria
    from AstraZeneca, Clovis Oncology,
    Pharma Mar and Tesaro; travel expenses
    from AstraZeneca and Roche; research
    funding from Merck Sharpe & Dohme; and
    a consultant role with Pfizer. Please see
    the abstract for all other authors’ relevant
    financial disclosures.
    Originally published on Healio.com/HemOnc | September 6, 2019
    PTSD may increase risk for ovarian cancer
    ymptoms of PTSD appeared associated with increased risk for ovarian cancer, especially among premenopausal women, according to study
    results published in Cancer Research.
    “In light of these findings, we need
    to understand whether successful treatment of PTSD would reduce this risk,
    and whether other types of stress are
    also risk factors for ovarian cancer,”
    Andrea Roberts, PhD, MPH, study coauthor and research scientist at Harvard
    T.H. Chan School of Public Health, said
    in a press release.
    Roberts and colleagues analyzed
    data from 49,443 women (mean age,
    34.6 years; 95.7% white) in the Nurses’
    Health Study II
    who were followed for up to
    26 years between
    1989 and 2015.
    The researchers validated selfreported ovarian cancer with
    medical records.
    They estimated
    risks for ovarian cancer with Cox proportional hazard models adjusted for
    known ovarian cancer and health risk
    In a supplemental questionnaire administered in 2008, the women reported lifetime PTSD symptoms from traumatic events, such as car accidents or
    assaults. They also identified the event
    they viewed as most stressful and the
    year of that event, as well as seven PTSD
    symptoms associated with the event.
    Researchers organized women into
    six groups according to PTSD symptoms following their worst trauma.
    Groups included no trauma exposure (reference group), trauma and no
    PTSD symptoms, one to three PTSD
    symptoms (subclinical), four to five
    symptoms (moderate), six to seven
    symptoms (high) and trauma with
    PTSD symptoms unknown.
    Researchers also examined associations by menopausal status.
    During follow-up, 110 cases of ovarian cancer occurred across 1.15 million
    Results showed that women with
    high PTSD symptoms had double the
    risk for ovarian cancer compared with
    women who had no trauma exposure (age-adjusted HR = 2.1; 95% CI,
    The association weakened only
    moderately after adjustment for health
    risk factors, such as smoking, and ovarian cancer risk factors, such as hormonal
    factors (HR = 1.86; 95% CI, 0.98-3.51).
    Separate analyses showed similar
    or stronger associations of high PTSD
    symptoms and ovarian cancer risk
    among women who had not been diagnosed with ovarian cancer at the time of
    the 2008 PTSD assessment (n = 50; ageadjusted HR = 2.38; 95% CI, 0.98-5.76)
    and among premenopausal women
    (HR = 3.42; 95% CI, 1.08-10.85).
    “Ovarian cancer has relatively few
    known risk factors. PTSD and other
    forms of distress, like depression, may
    represent a novel direction in ovarian
    cancer prevention research,” Shelley
    Tworoger, PhD, study co-author and
    associate director of population science
    at Moffitt Cancer Center, said in a press
    release. “If confirmed in other populations, this could be one factor that doctors could consider when determining
    if a woman is at high risk [for] ovarian
    cancer.” – by John DeRosier n
    Roberts AL, et al. Cancer Res.
    Disclosures: The authors report no relevant
    financial disclosures.
    Shelley Tworoger
    continued from previous page
    8 | December 10, 2019 | Healio.com/HemOnc
    Originally published in HemOnc Today | Juky 25, 2019
    Olaparib prolongs PFS in BRCA-mutated,
    platinum-sensitive ovarian cancer
    Olaparib monotherapy significantly improved overall
    response rates and PFS, with
    no new safety signals, compared with
    nonplatinum chemotherapy among
    women with germline BRCA-mutated, platinum-sensitive relapsed ovarian cancer, according to results of the
    randomized phase 3 SOLO3 study.
    “SOLO3 is the first phase 3 randomized trial of a PARP [poly(ADPribose) polymerase] inhibitor vs.
    nonplatinum-based chemotherapy
    in women with [platinum-sensitive
    relapsed] germline BRCA-mutated
    ovarian cancer,” Richard T.
    Penson, MD,
    associate professor of medicine at Harvard
    Medical School
    and clinical director of medical gynecologic
    oncology at
    Massachusetts General Hospital,
    said during the presentation. “A statistically significant and clinically
    relevant improvement in [overall response rate] and PFS was observed
    with olaparib and chemotherapy vs.
    nonplatinum-based chemotherapy.”
    Olaparib (Lynparza, AstraZeneca) demonstrated efficacy vs.
    pegylated liposomal doxorubicin in
    a randomized phase 2 trial that included women with BRCA-mutated
    ovarian cancer who experienced recurrence within 12 months of prior
    platinum therapy. The efficacy of pegylated liposomal doxorubicin, however, appeared higher than previously observed in this setting, according
    to study background.
    In the confirmatory phase 3
    study, Penson and colleagues randomly assigned 266 patients with
    BRCA-mutated, platinum-sensitive
    relapsed ovarian cancer in a 2:1 ratio to 300 mg twice-daily olaparib
    (n = 178) or physician’s choice of
    chemotherapy (n = 88) that included paclitaxel (n = 20), topotecan
    (n = 8), gemcitabine (n = 13) or
    pegylated liposomal doxorubicin
    (n = 47). Treatment continued until
    disease progression.
    Researchers stratified women
    by chemotherapy treatment, prior
    lines of chemotherapy (2 to 3 vs. 4
    or more) and platinum-free interval (6-12 months vs. more than 12
    ORR served as the trial’s primary
    endpoint. PFS and safety served as
    secondary endpoints.
    Twelve patients in the chemotherapy group withdrew before
    receiving treatment, and 223
    had baseline measurable disease
    (olaparib, n = 151; chemotherapy,
    n = 72).
    Results showed an ORR of 72%
    in the olaparib group vs. 51% in the
    chemotherapy group (OR = 2.53;
    95% CI, 1.4-4.58).
    Patients in the olaparib group
    demonstrated significantly longer median PFS than the chemotherapy group as measured by
    blinded independent central review (13.4 months vs. 9.2 months;
    HR = 0.62; 95% CI, 0.43-0.91) and
    by investigator assessment (13.2
    months vs. 8.5 months; HR = 0.49;
    95% CI, 0.35-0.7).
    This study is unique because it is not looking at olaparib
    as a maintenance therapy for platinum-sensitive recurrent ovarian cancer. It is looking at upfront use of the
    PARP inhibitor in the recurrent setting and comparing it
    with the standard of care, which is chemotherapy.
    The findings were very interesting because the response
    rates were favorable with olaparib vs. traditional chemotherapy and the HR was better. Looking at these results,
    I think we could see olaparib used in the upfront setting
    instead of as a maintenance therapy.
    One of the big things is toxicity. Generally, the toxicity was not any different
    than with chemotherapy and there wasn’t anything too worrisome. Going
    forward, for patients with recurrent disease, we can consider using olaparib
    instead of chemotherapy to start with.
    This is a very provocative and interesting study, and I think it could lead to
    big changes moving forward.
    Linus Chuang, MD
    Western Connecticut Health Network
    Disclosure: Chuang reports no relevant financial disclosures
    Linus Chuang
    Richard T. Penson
    Olaparib continues on next page
    9 | December 10, 2019 | Healio.com/HemOnc
    Originally published in HemOnc Today | November 25, 2019
    Navicixizumab receives fast track
    designation for pretreated ovarian cancer
    he FDA granted fast track designation to navicixizumab for the
    treatment of women with heavily
    pretreated high-grade ovarian, primary peritoneal or fallopian tube cancer.
    The designation applies to use of
    navicixizumab (Mereo BioPharma)
    — an anti-Delta-like ligand 4/vascular
    endothelial growth factor bispecific
    antibody — for women who received at
    least three prior therapies and/or prior
    bevacizumab (Avastin, Genentech).
    “We are pleased that the FDA
    continues to recognize the potential
    of navicixizumab to become a viable
    new treatment option for patients with
    platinum-resistant ovarian cancer
    who failed multiple other therapies,”
    Jill Henrich, senior vice president of
    regulatory affairs at Mereo BioPharma,
    said in a company-issued press release.
    A phase 1a study assessed
    navicixizumab monotherapy for
    patients with various types of
    refractory solid tumors. Nineteen
    (28.7%) of 66 patients had tumor
    shrinkage after treatment, and 12
    (25%) of the women with ovarian
    cancer treated on the trial achieved
    unconfirmed partial response.
    An ongoing phase 1b study is
    designed to evaluate the agent in
    combination with paclitaxel for
    women with advanced heavily
    pretreated ovarian cancer. The study
    includes 44 women with platinumresistant disease who failed more than
    two prior therapies and/or received
    prior bevacizumab.
    An interim analysis performed
    earlier this year showed an
    unconfirmed response rate of 41%,
    with overall response rates of 64%
    for bevacizumab-naive women and
    30% for those who received prior
    bevacizumab. Median PFS in the
    entire cohort was 7.3 months.
    The most common any-grade related
    adverse events were hypertension
    (68%), fatigue (46%), headache
    (25%), neutropenia (21%), diarrhea
    (18%), pulmonary hypertension
    (14%), dyspnea (14%) and peripheral
    edema (14%). Other related adverse
    events of special interest included
    one grade 1 heart failure; two cases
    of thrombocytopenia, one grade 3
    and one grade 4; and one grade 4
    gastrointestinal perforation.
    In July, the FDA agreed in principle
    on an outline for a phase 2 trial that
    could support accelerated approval
    of navicixizumab for women with
    ovarian cancer who developed
    resistance to previous therapies,
    Henrich said. n
    The safety profiles of olaparib
    and chemotherapy were consistent
    with previous data, according to
    Penson. Common adverse events
    with olaparib vs. chemotherapy
    included nausea (65% vs. 34%)
    and anemia (50% vs. 25%). The
    most common adverse event with
    chemotherapy was palmar-plantar
    erythrodysesthesia (36% vs. 1%).
    Serious adverse events occurred
    among 24% of patients in the olaparib
    group vs. 18% in the chemotherapy
    group. However, Penson noted that
    patients in the chemotherapy group
    appeared more than twice as likely
    (20% vs. 7%) to discontinue study
    treatment because of an adverse
    “[Overall], SOLO3 provides
    important prospective data on the
    efficacy of these treatment options
    for women with heavily pretreated,
    PSR germline BRCA-mutated
    ovarian cancer,” Penson said.
    – by John DeRosier n
    Penson RT, et al. Abstract 5506. Presented at:
    ASCO Annual Meeting; May 31-June 4, 2019;
    Disclosures: Penson reports consultant
    roles wit

  • CancerNews' Avatar

    CancerNews posted an update

    Are you exercising? Doctors are now "prescribing" it for patients who might not be getting enough.

    Doctors are now prescribing this ‘treatment’ to fight cancer
    Naveed Saleh, MD, MS, for MDLinx | December 09, 2019

    Once upon a time, patients with cancer were advised to rest and relax, especially after cancer treatment such as chemotherapy, so as not to strain themselves. This isn’t so much the case today, when exercise is encouraged for this patient population—and even dosed into treatment regimens.


    The ACSM recommends that all physicians ask their patients with cancer about physical activity, and if inadequate, recommend more.
    The ACSM recommends that all physicians ask their patients with cancer about physical activity, and if inadequate, recommend more.

    In the 1990s and 2000s, evidence cropped up that contraindicated previous beliefs that exercise was bad for patients with cancer. In turn, these studies laid the foundation for the burgeoning field of exercise oncology. Today, there are more than 1,000 randomized, controlled trials on the topic.

    In October 2019, the American College of Sports Medicine (ACSM) convened an expert panel to report recently updated guidelines regarding the role of exercise in cancer survivorship. Let’s take their results from the top, and focus on the role of exercise as a cancer treatment.

    Benefits of exercise in cancer
    “The ACSM panel found evidence that providing specific exercise prescriptions for a number of cancer-related health outcomes benefitted people living with or beyond cancer,” said former ACSM president and panel co-chair Kathryn Schmitz, PhD, MPH, professor, Departments of Public Health Sciences and Physical Medicine and Rehabilitation, Penn State College of Medicine, Hershey, PA. “As an example, we saw strong evidence that an exercise program consisting of a half hour of aerobic exercise three times weekly was sufficient to improve anxiety, depression, fatigue, quality of life, and physical function in cancer survivors.”

    SEE ALSO: Combine these two foods to protect against lung cancer
    Concerns about lymphedema secondary to twice-weekly resistance training have been raised, but the panel found this type of exercise did not increase the risk of disease and even offered some health benefits. However, compared with resistance training alone, symptoms of depression and anxiety have only been shown to improve with resistance training combined with aerobic training.

    It remains to be elucidated whether exercise also improves other cancer-related outcomes—including cardiotoxicity, peripheral neuropathy, pain, cognitive function, or chemotherapy completion rate—as well as whether exercise boosts treatment tolerance.

    In terms of survivorship, exercise prescribed to patients with colon, breast, or prostate cancers has been linked to lengthened survival. However, not enough evidence exists regarding potential survival benefit in those with other types of cancer. On a related note, the ACSM recommends that all cancer survivors heed to general public health recommendations for physical activity, which is either 2.5 to 5.0 hours per week of moderate-intensity activity or 1.25 to 2.5 hours per week of vigorous activity.

    Exercise prescription
    Years ago, it was unclear to most that exercise is good for the heart, and now everybody knows this thanks to a paradigm shift. Similarly, the ACSM hopes for a paradigm shift in how providers, caregivers, and patients with cancer view exercise as beneficial and necessary in treatment.

    “ACSM has just started a new initiative called Moving Through Cancer,” said Dr. Schmitz, “which focuses on increasing awareness of the value of exercise for cancer survivors, along with educating the cancer clinician workforce to refer, coordinate, and prescribe exercise; expanding opportunities to exercise; and shifting policy so that, by 2029, exercise is standard practice for all patients living with and beyond cancer.”

    Importantly, any exercise regimen needs to be personalized to patient preference and functional status. Factors including age, cancer type/stage, adverse effects of treatment, and comorbidities should be taken into consideration.

    Counseling patients
    Lots of people with cancer don’t exercise. These patients should be advised to try some type of physical activity as a means to improve their health. Simply going from no exercise to some exercise is a great improvement. The ACSM recommends that all physicians ask their patients with cancer about physical activity, and if inadequate, recommend more.

    SEE ALSO: Novel, high-accuracy blood test can screen for multiple cancers
    “Even if that is all providers have time to do, it demonstrates to patients that physical activity is an important part of managing their health and lays out the expectation that being physically active is healthier than being sedentary,” said Dr. Schmitz. “This is true even for patients with advanced disease and those experiencing limitations, although those cancer patients will need a medically supervised program.”

    Bottom line
    Physicians are busy professionals. Unpacking the benefit of exercise for your patients will take precious minutes. However, many patients with cancer enjoy exercise programs greatly, and appreciate the guidance in retrospect. Focusing on exercise can be a productive and empowering portion of the clinical encounter.

    In interested in learning more, the Moving Through Cancer initiative’s website provides ample information on high-quality exercise programs and answers to frequently asked questions. Keep in mind that physicians need to refer patients to exercise programs, with most exercise programs requiring physician approval.

    1 Comment
    • Bengal's Avatar

      My oncologist referred me to PT for "maintenance" . I went twice a week and did strength and endurance training (easy level). The fact that I had a schedule insured that I did do it whereas left to my own devices at home..... I always felt invigorated when I left PT then drove home and passed out on the couch and slept Lol. But, that was good too because it was good sleep brought on by being tired out not the restless tossing and turning at night. I think PT was very helpful and would definitely recommend it.

      about 1 year ago
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    CancerNews posted an update

    Suffering from “chemo brain”? There’s hope and many things you can do

    101 Tips for Tip-Top Health, is yours absolutely FREE when you sign up to receive Health Alerts from Harvard Medical School

    HEALTHbeat, our complimentary email newsletter brings you tips for living a healthy lifestyle, with ways to fight inflammation and improve cognitive health, plus the latest advances in preventative medicine, diet and exercise, pain relief, blood pressure and cholesterol management, and more.

    Click here to get the Article 101 Tips For Tip-Top Health

  • CancerNews' Avatar

    CancerNews posted an update

    Cancer Survivorship And Age
    A two-time cancer survivor explores her thoughts on aging.
    Barbara Tako is a breast cancer survivor (2010), melanoma survivor (2014) and author of Cancer Survivorship Coping Tools–We'll Get You Through This. She is a cancer coping advocate, speaker and published writer for television, radio and other venues across the country. She lives, survives, and thrives in Minnesota with her husband, children and dog. See more at www.cancersurvivorshipcopingtools.com,or www.clutterclearingchoices.com.
    I am now one of "those" people. You know, someone who has some gray hair and talks about health worries, procedures, medications and medical concerns with fellow aging folks. Fall is now a metaphorical life stage as well as a seasonal event. And yet: I still feel young inside! I suspect many of us do. My feelings include some satisfaction at my achievements, but there are also hopes and dreams not yet experienced. It may be helpful for cancer survivors and others to ponder aging.

    In my forties, cancer pitched me into early post-menopause, then osteopenia (loss of bone mass), permanent hair loss and brittle hair, and then finally neuropathy (numbness in the foot I "coincidentally" rolled and broke a couple years ago). Cancer is the unwanted gift that just seems to keep on giving. I am grateful to be here. I would just like fewer cancer reminders and signs of deterioration. Who wouldn't?

    A person could mope or make the best use of the time that is left. I just finished It's Never Too Late To Begin Again, and I am currently working on You Can Draw In 30 Days. I also have an upcoming MRI to look at my pancreas because of my PALB2 cancer mutation and a vague plan in my mind to see an endocrinologist and join a fitness gym (again) to work on my fatigue. I learn that I can do new things and be responsible about my ongoing healthcare.

    Life feels strangely in flux as we experience our fifties, sixties, and beyond. I am trying to float gently with it. Will we sell our home? Will we spend part of the year somewhere warm? The answer today is maybe, but not quite yet. It is fun and disconcerting to ponder and to be open to options. I am grateful to have options and possibilities while at the same time I fret at the lack of a clear plan. Sound familiar? We are not alone - there are resources to help!

    Some of the later life worries are the same ones I always had: how can I help aging relatives, will our kids be okay, will we run out of money. Faith helps a lot, and I am learning that exploring hobbies and completing home projects does not always have to be expensive. I can even work on what I eat and how I move. I can educate myself with reliable sources on the Internet. I can buy used books and inexpensive supplies from a dollar store. These experiences can be the same regardless of whether I am a cancer survivor or not. It just makes me happy to be here today!

    Fall is a great opportunity to evaluate, make some fun new choices, and break yourself out of your usual routines. Don't let cancer or fear of its return paralyze you. Sit down, write a bucket list, and then don't wait - get to it! The seasons of life will come and go much too quickly. Within those brief windows of time, we still have the opportunity to make choices and have new experiences. Don't give up even when, like me, you suddenly realize you too may be turning into one of "those" people.

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    The worst thing about being strong is that no one ever asks you if you're OK.

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    NJ hospital provides targeted radiation therapy, reducing side effects

    Unlike typical radiation, proton therapy doesn’t send radiation clear through the body and it keeps the radiation from affecting healthy tissue.

    “Because it exits you would have low-dose radiation in the front of the body. But proton, we’re able to tell it to stop when we need it to, so you could see, right past the target it stops completely,” said Rihan Davis, radiation oncology chief dosimetrist at the Laurie Proton Therapy Center, which is part of Robert Wood Johnson University Hospital, an underwriter of NJTV News. The center provides proton therapy in partnership with Rutgers Cancer Institute of New Jersey.

    Dr. Rahul Parikh, the center’s medical director, talks about some of the misconceptions with this therapy.

    “One of the biggest myths is that perhaps proton therapy is more precise or more accurate. In fact, it’s just as precise as standard radiation, it’s really about the physical properties as you’ve heard, the physical properties of the proton beam,” Parikh said.

    He gives the example of a pediatric brain tumor where the tumor is sitting in part of the brain where nearby structures are extremely important – whether it be brain tissue or nerves.

    With proton therapy, all the radiation can be delivered to one particular area with little to no dose of radiation elsewhere, sparing healthy and critical tissue.

    “When we’re in a tricky location, where surgery can’t be done or can’t be done effectively enough to cure the patient, and we have to deliver high doses of radiation, that go above the tolerability of the structures and nearby organs, that’s when we think about proton therapy,” Parikh said.

    The radiation is emitted through the opening of a brass ring — the opening is shaped and custom-made for the patient. An additional piece of the brass helps block out nearby critical structures from receiving radiation.

    But this technology is expensive. There are only two proton centers in the state. NJTV News was granted access to the basement of the facility to see the machine behind the therapy.

    “To accelerate protons, which is necessary to provide treatment, we start with hydrogen gas. There’s a little bottle, and we pump in just a small amount of hydrogen gas into the center of the accelerator,” said Aaron Devoe, field service engineer for Mevion Medical Systems. “So once the gas is pumped in, we apply a high voltage, and we’re able to isolate the protons. So once the protons are in the center of the accelerator, we induce an electrical field on those protons to start accelerating.”

    “So before the protons will exit the machine, they’ll have done about 75,000 revolutions, and they’re going about three cores the speed of light when they exit,” Devoe said.

    “That’s where the proton therapy is different it causes direct damage to the DNA of the cancer cell selectively. Whereas standard photons or X-rays use a secondary method. They often cause these free radicals and cause oxidated damage that can secondarily affect the DNA of the cancer cells, and then they try to reproduce and they cannot,” Parikh said.

    Parikh says while the cure rate is the same for proton therapy and other forms of radiation, patients treated with proton therapy do have less side effects.

    More research is being done to see if there is value in adding proton therapy to treating other cancers like lung, breast and prostate.

    Watch the video and read original article on NJTV Online

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    Bad News Over the Phone, a Current Trend that Needs to Change
    Should patients be given a choice on how they wish to receive bad news? One survivor seems to think so.

    JUNE 14, 2019
    Bonnie Annis is a breast cancer survivor, diagnosed in 2014 with stage 2b invasive ductal carcinoma with metastasis to the lymph nodes. She is an avid photographer, freelance writer/blogger, wife, mother and grandmother.

    In 2014, when the call came from the oncologist’s office, I assumed it was to set up an appointment. A few days earlier I’d had several tests performed, including a mammogram, a diagnostic ultrasound and a core needle biopsy. What I didn’t expect was to receive life-changing information in four words.

    Instead of being offered options for an office visit to discuss test results, I was given the news that I had cancer. The information came from a doctor of pathology, a doctor I’d never met. And while she did apologize for being the bearer of bad news, I had to face that devastating phone call alone.

    I assumed, when the mammogram led to more testing, I more than likely had cancer. Although I wasn’t sure. I also assumed, when it was time for the results to be shared with me, I’d be called into the doctor’s office and the blow would have been made a little softer by a face to face discussion.

    But apparently, my case wasn’t an isolated one. According to a study performed by the University of Missouri School of Medicine, more and more people are receiving bad news via telephone. The study was conducted in an effort to determine how patients received their diagnoses. According to the University of Missouri School of Medicine, “The research revealed prior to 2007, about 25% of patients learned of their diagnosis over the telephone. After 2007, that number increased to more than 50 %. Since 2015, that number has grown to 60%. When we analyzed the data, I was completely surprised to find such a clear trend,” said Dr. Jane McElroy, professor of family and community medicine at the MU School of Medicine and lead author of the study. “Historically, physicians have decided to use their best judgment when delivering a diagnosis, whether it’s in person or over the phone. Nowadays, some patients clearly want to hear this information over the phone.”

    In today’s world of instant knowledge, do we really want to receive life-changing news over the phone? Personally, I prefer face to face interaction. That way I can not only hear the words that are being shared; I can also watch body language which often reveals a lot more information.

    When I received the news that I had breast cancer, I couldn’t tell you what the pathologist said after those initial words. My brain shut down. I couldn’t process any more information. Perhaps I was in shock, and rightly so. Whatever the case, I’d have preferred not to have received that important news in such an impersonal way. I’d be willing to bet there are others who feel the same way.

    The University of Missouri School of Medicine is taking into account the way patients prefer the delivery of health news. Dr. Natalie Long, assistant professor of clinical family and community medicine at the MU School of Medicine says, “We are now including additional training for first-year medical students to talk about situations and techniques for breaking bad news over the phone. The digital age has changed our perception of how we want to get news. I think younger patients just want to know news faster.” Long also said, “Many of the same principles taught for delivering bad news in person can be applied to phone conversations. The key is learning beforehand how the patient wishes to be informed. Best practices include making sure the patient is in a good place to talk, using good listening skills, showing empathy, ensuring the patient has a support system around them and developing a follow-up plan.”

    I applaud this university for changing their curriculum by helping sensitize the medical students toward better communication with patients. Although the world we live in today offers instant access and delivery of most anything we choose to know, I’m old school. I want a doctor to sit down with me, have a heartfelt conversation about what’s going on with my body and help me understand how we’re going to fix it. Bad news needs to be handled with kid gloves. Good news, on the other hand, in my humble opinion, can be delivered by any means necessary. I’d even be willing to receive it via two tin cans and a string.

    Maybe soon, doctors will begin routinely asking patients how they’d prefer to receive test results. That way, those who prefer telephone communication could receive it and those who prefer face to face could have their needs met, too.

    I wouldn’t be surprised if in the near future, doctors text or even FaceTime bad news. I’m not going to agree to either of those means of delivery and I hope you won’t either.


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    Cancer Gifts: Reaching a Milestone

    I hear friends talk about feeling old and the resisting the natural process of aging. “Old” for me was a dream and a wish. Now I rejoice in every wrinkle as an affirmation that I am getting older. Yahoo. I can’t wait to be 70.

    Kathy LaTour is a breast cancer survivor, author of The Breast Cancer Companion and co-founder of CURE magazine. While cancer did not take her life, she has given it willingly to educate, empower and enlighten the newly diagnosed and those who care for them.

    This summer I am going to be 70. It's a significant milestone in anyone's life, but and it does make me take pause and look back at my life.

    For many of you, cancer is a new or relatively new experience. I was diagnosed 32 years ago at age 37, and if you are wondering why I am still thinking and writing about it, here is the deal.

    Many of us only spend a few months in treatment for something that will, possibly, affect us for the rest of our lives. I was diagnosed at the beginning of the recognition that survivorship is a distinct part of the cancer experience. Today, cancer centers are expected to offer survivorship care plans at the end of treatment as well as programs to help patients deal with social, emotional and practical issues of cancer.

    This has become my area of research, concern and expertise and we have come a long way. But we also have a long way to go. One young woman I know was treated for a sarcoma at age 19. It involved a year of treatment and, while she Is now In her mid 40s, It took her until her mid 30s to resolve her cancer experience emotionally. Last week at my insistence, she visited a cardiologist to get a baseline and it turns out she has cardiomyopathy, a serious heart condition.

    This is one reason I keep researching survivor issues as I deal with my own, mild congestive heart failure and neuropathy.

    Luckily for me, it only took me a few years of fear and misery after my diagnosis to realize I needed help. Having a one-year-old motivated me to find help so I could be the mother I wanted to be. It took me to a place that allowed me to heal into my cancer.

    The birthdays that I had always dreaded were now celebrations that I had made it another year. This is not how I felt before cancer when, with 40 approaching and a new baby, I spent my time feeling like the mommy track had derailed my life and I would never get it back.

    Now I rejoice in every wrinkle as affirmation that I am getting older. Yahoo. I can’t wait to be 70.

    I hear friends talk about feeling old and the resisting the natural process of aging. “Old” for me was a dream and a wish. Sometimes I want to say, “Hey, you want to feel young and appreciate every day?”

    They’ll ask, “How?”

    I will reply, “Get cancer.”

    1 Comment
    • beachbum5817's Avatar

      Thanks for the article. I will turn 65 next month, and I feel exactly the same way.

      over 1 year ago
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    In the featured podcast, Dr. Peter Attia interviews professor Thomas Seyfried, Ph.D., recipient of our Game Changer Award in 2016 for his work on cancer as a metabolic disease, which is also the title of Seyfried’s book1 on this topic. His work is also heavily featured in Travis Christofferson’s excellent book, “Tripping Over the Truth: The Metabolic Theory of Cancer.”

    The actual podcast can be heard on Dr. Attia’s site

    Seyfried, in my view, is simply the best cancer biologist in the world. The featured interview2 goes into great technical detail that can be challenging for some, but if you’re interested in understanding the mechanics of cancer, I highly recommend taking the time to listen to it in its entirety, especially toward the end.

    Without a doubt, it is one of the finest detailed discussions about why cancer cells grow and how conventional medicine has it mostly wrong when it comes to treatment, especially radiation and chemo. Without a doubt, it is one of the best interviews Seyfried has ever done. Although Attia is a Harvard trained physician with oncology training, he frequently disagrees with Seyfried, who schools him in the basics.

    I have listened to the entire interview twice and learned even more the second time. Now I have a fairly good background on this topic so if you are new to it and have a loved one who needs this information you may need to listen a few times. Toward the end of the interview Seyfried gets into some very important principles in cancer treatment, such as:

    Being careful to avoid biopsies if at all possible as they are strongly related to allowing the cancer to metastasize.
    Surgical therapy can be a useful intervention but it should be delayed as long as possible while the patient is on metabolic therapy so the tumor will shrink and allow the margins to be more well defined so it can be removed more easily.
    Avoid radiation and chemotherapy at all costs as they typically impair the immune system that is ultimately responsible for resolving the tumor.
    More than 1,600 people die from cancer every DAY in the U.S., but 8,100 die from cancer every day in China, where the problem is far worse. Remember these are deaths per day, not cancer diagnosis.
    It is vital to understand that more people die from cancer treatment than the cancer itself.
    Introduction to Cancer as a Metabolic Disease

    The established dogma that cancer is a genetic disease currently rules everything, from the research that receives funding to the treatment you can expect from an oncologist. Indeed, this dogma is what fuels the entire cancer industry. Unfortunately, it’s not leading to any significant breakthroughs in treatment, let alone prevention.

    Seyfried and others have been able to advance the theory that cancer is primarily the result of defective energy metabolism in and damage to the cells’ mitochondria. Simply put, genetic mutations are not the primary cause of cancer but are rather a downstream effect of the defective energy metabolism. As long as your mitochondria remain healthy and functional, your chances of developing cancer are actually slim.

    According to Seyfried, while it’s still poorly understood how a ketogenic diet works to subdue epileptic seizures, the mechanism of action on cancer cells is really clear, and is based on the pioneering findings of Dr. Otto Warburg, a classically trained biochemist who in 1931 received the Nobel Prize in Physiology or Medicine for his discovery of the nature and mode of action of the respiratory enzyme cytochrome C oxidase.3

    Warburg’s work shows how cells obtain energy from respiration, and how cancer cells have a fundamentally different energy metabolism compared to healthy cells (see section on Warburg Effect below).

    Following in Warburg’s footsteps, research by Seyfried and others show that cancer is primarily a metabolic disease involving disturbances in energy production through respiration and fermentation in the cells. Studies have actually shown that cancer is suppressed when the nucleus from a tumor cell is transferred to cytoplasm of normal cells with normal mitochondria.

    What this tells us is that normal mitochondria suppress cancer growth, and in order for cancer cells to proliferate, you must have dysfunctional mitochondria.

    Seyfried’s research has shown that cancer growth and progression can be managed following a whole-body transition from fermentable metabolites, such as glucose and glutamine, to respiratory metabolites, primarily ketone bodies that are formed when you follow a ketogenic diet. This transition reduces tumor vascularity and inflammation while enhancing tumor cell death.

    Source: peterattiamd.com. Image credit: Thomas Seyfried

    The Warburg Effect

    Warburg discovered that even in the presence of oxygen, cancer cells derive energy from the ancient process of anaerobic fermentation (sometimes called glycolysis), which causes an overproduction of lactic acid. This is known as the Warburg Effect:

    Aerobically, in the mitochondria
    Anaerobically, in the cytoplasm, which generates lactic acid, a toxic byproduct in high concentrations
    Aerobic respiration is far more efficient, capable of generating more than 30 times more adenosine triphosphate (ATP) than anaerobic energy generation. As explained in the featured interview, normal, healthy cells will produce very minimal amounts of lactic acid in the presence of oxygen. Cancer cells, on the other hand, behave very differently.

    Cancer cells continue to produce massive amounts of lactic acid, even in a 100-percent oxygen environment, which caused Warburg to conclude that the primary cause of cancer is that the respiratory system of cancer cells is defective, causing the cells to revert from healthy aerobic energy generation to unhealthy anaerobic fermentation. You can read Warburg’s 1956 paper4 “On the Origin of Cancer Cells” here.

    Please note that respiratory system in this context does not refer to the lungs but rather to the processing of oxygen from the lungs in the electron transport chain of the mitochondria that ultimately passes the electrons from your food to oxygen to create water and ATP.

    So, in a nutshell, what Warburg discovered is that cancer cells have dysfunctional mitochondria — hence the claim that cancer is a metabolic disease rooted in mitochondrial dysfunction.

    Different Types of Mitochondrial Abnormalities Are Found in Cancer Cells

    One of the primary reasons why modern researchers have failed to realize that all cancer cells have impaired respiration is because they started researching cancer using cell cultures, and when you separate the cells from the tissue and grow it in a medium, it causes them to behave in ways they normally wouldn’t when in the animal or human.

    Hence many researchers have claimed that cancer cell respiration is normal, when in fact it is not. According to Seyfried, during in vitro or culture research, it looks like cancer cells consume a lot of oxygen, even when producing lactic acid, which creates confusion.

    He does point out that while all cancer cells have defective mitochondria, how that defect came about will vary from one cancer to another. In some cancers, there’s simply a lack of mitochondria, meaning the cell does not have enough organelles to generate energy through respiration and therefore falls back on fermentation as a source of energy production.

    In other cancers, the cells appear to have plenty of mitochondria, but the organelles are structurally abnormal. As noted by Seyfried, “structure dictates function,” so if the structure of the mitochondria is abnormal, its function will also be abnormal. However, all cancer cells use fermentation for energy production. Seyfried has not found a single cancer with normal respiration.

    In order to grow and spread, cancer cells also need ample building blocks, which Seyfried says they get from the pentose phosphate pathway, the glycolytic pathway and from glutamine. “Between glucose and glutamine, you’re getting all the building blocks you need for rapid cell division,” he says.

    Cancer Is Not a Gene-Driven Disease

    Seyfried also stresses that in his research, no genetic abnormalities were found in cancer cells at all, which firmly disputes the genetic theory which postulates that cancer is driven by genetic mutations. Sadly, Attia is still convinced that the gene theory of cancer is true. It’s quite sad that such a brilliant and innovative physician fails to appreciate the depth of beauty of Seyfried’s work.

    Overall, an estimated 5 percent of cancers are caused by germline mutations, such as BRCA1, an inherited genetic risk factor known to raise your risk for breast cancer, or BRCA2, which raises your risk for ovarian cancer.

    But as noted by Seyfried, “They’re not deterministic.” A certain gene mutation may raise your risk, but it’s no guarantee you will actually develop the cancer in question, and it is ultimately not the true cause if you do get cancer. An exception is if the mutation damages the mitochondria’s respiratory system; then cancer is a very real possibility.

    Warburg’s Missing Link

    The featured interview also delves into the details of mitochondrial substrate level phosphorylation (mSLP) — the missing link in Warburg’s cancer theory. When mitochondria are damaged, causing them to revert to such an inefficient form of energy production, how is it that they have enough energy to massively reproduce and grow?

    For years, Seyfried suspected glucose fermentation wasn’t the whole story, and his research shows cancer cells can in fact ferment not only glucose but also glutamine, and the majority of the energy for cancer formation actually comes from the glutamine.

    Glutamine is fermented via mSLP in the tricarboxylic acid (TCA) cycle — also known as the Krebs cycle — of the mitochondria. The TCA or Krebs cycle is a series of chemical reactions catalyzed by enzymes that form a key part of aerobic respiration. Seyfried explains:

    “mSLP is the production of ATP when you move a phosphate group from an organic substrate onto an ADP molecule, so it’s an ancient way of generating energy. In other words, it’s an organic molecule that is an electron acceptor rather than oxygen …

    You’re moving phosphate groups from an organic substrate onto the ADP as the acceptor, and you can generate massive amounts of energy from this process which can replace the level of lost energy from the damaged mitochondria …

    In the normal cell, you’re making most of your ATP from oxidative phosphorylation, but in the cancer cell you’re making most of it from mSLP inside the same organelle [i.e., the mitochondria].”

    Source: peterattiamd.com. Image credit: Thomas Seyfried

    Source: peterattiamd.com. Image credit: Thomas Seyfried

    Why Cancer Cells Don’t Self-Destruct

    Another question of import is “Why don’t cancer cells die through the apoptotic mechanisms?” meaning the mechanism that triggers cellular suicide when the cell is damaged or malfunctioning. In short, because the mitochondria that actually controls that self-destruct “switch” is dysfunctional.

    “The cell bypasses the normal control of life and death — apoptosis of the cell — because the very organelle that dictates that is [the mitochondria], is now defective,” Seyfried says. As a consequence, the cell reverts back “to the way it existed before oxygen came into the atmosphere on the planet.”

    Healthy Mitochondrial Respiration Prevents Cancer Formation

    The take-home message here is that as long as your mitochondrial respiration remains healthy, cancer will not develop. “That goes back to prevention,” Seyfried says. “How do you prevent cancer? You prevent it by keeping your mitochondria healthy.”

    And how do you keep your mitochondria healthy? Primarily by avoiding toxic environmental factors and implementing healthy lifestyle strategies. This is in fact the sole focus of the metabolic mitochondrial therapy program detailed in my book “Fat for Fuel.” Topping my list of strategies to optimize mitochondrial health — which you can learn more about in my book — are:

    Cyclical nutritional ketosis — The divergence from our ancestral diet — this massive prevalence of processed, unnatural foods and excessive amounts of added sugars, net carbs and industrial fats — is responsible for a majority of the damage to your mitochondria.

    High-carb, processed food diets prevent your body from efficiently burning fat as its primary fuel, and burning fats and ketones is far more efficient, inducing far less oxidative stress, than burning carbs. So, a foundational dietary strategy to optimize your mitochondrial health is to eat the right fuel. Once you become an efficient fat burner, you minimize the oxidative stress placed on your mitochondria, which is key.

    Calorie restriction — Another extremely effective strategy for reducing mitochondrial free radical production is to limit the amount of fuel you feed your body. This is a noncontroversial position as calorie restriction has consistently shown many therapeutic benefits.

    Meal timing — Meal timing is also important. Specifically, eating too late in the evening, when your body doesn’t need the energy, is one of the worst things you can do to your mitochondria, as it creates a buildup of ATP that is not being used.

    As a result, it’s not being broken down into ADP, causing ATP synthase to shut down. At that point, the entire electron transport chain backs up, causing excessive amounts of free radicals to spill out and damage the mitochondrial DNA.5

    Normalizing your iron level — Iron also plays an important role in mitochondrial function, and contrary to popular belief, excessive iron levels are far more prevalent than iron deficiency. Virtually all men over the age of 16 and post-menopausal women are at risk of high iron.

    Menstruating women are protected since they lose blood, and hence iron, each month. While most people damage their mitochondria by eating a high-carb, low-fat diet and/or excessive protein, elevated iron levels can cause profound mitochondrial damage as well.

    When you have high iron levels in your mitochondria, it enhances oxidation, creating high levels of damaging reactive oxygen species and free radicals. Fortunately, high iron is easy to address. Simply check your iron level with a serum ferritin test, and if your level is high, donate blood two or three times a year to maintain a healthy level.

    An ideal iron ferritin level is between 40 to 60 nanograms per milliliter (ng/mL). Below 20 ng/mL is a deficiency state, and you definitely do not want to be above 60 or 80 ng/mL.

    An important side note to this is that excess carbohydrates in particular, when eaten late at night, result in a backup of electrons, causing the production of superoxide. While not a pernicious free radical in and of itself, if you have high iron levels combined with high superoxide, it produces hydroxyl free radicals, which is one of the most harmful.

    The chemical reaction that creates these hydroxyl free radicals is known as the Fenton reaction. While you certainly need enough iron, having too high an iron level can cause severe damage, and this is one way in which it does that.

    Exercise — Exercise upregulates PGC-1 alpha and Nrf2 — genes that promote mitochondrial efficiency, helping them grow and divide so that you actually have more mitochondria.

    In simple terms, by placing an increased energy demand on your cells through physical activity, free radicals signal that you need more mitochondria to meet the energy demand. As a result, your body adapts to your level of activity by creating more mitochondria and making them work more efficiently.

    Interestingly, in his book “Mitochondria and the Future of Medicine,” Dr. Lee Know, a naturopathic physician, explains how some people need more exercise to maintain mitochondrial health.6When hydrogen ions flow back through ATP synthase, energy is created. But in some cases, and in certain tissues, such as in brown adipose tissue, this process can become uncoupled.

    Instead of the hydrogen ions flowing back through ATP synthase, they flow through a different channel, creating heat rather than energy. A benefit of this is that it allows the electron transport chain to continue to operate even though you’re not using up energy. The hydrogen gradient is being dissipated through the generation of heat instead.

    If your genetic heritage stems from equatorial regions and/or if you have very dark skin, you will tend to have less brown fat, and hence less mitochondrial uncoupling, which raises your risk of chronic disease. To counteract this, you will need to exercise regularly. Also, be mindful of your vitamin D level, and consider cold thermogenesis (cryotherapy) to build brown and beige adipose tissue.

    Nutritional supplements — The following nutrients and cofactors are also needed for mitochondrial enzymes to function properly:

    CoQ10 or ubiquinol (the reduced form)
    L-Carnitine, which shuttles fatty acids to the mitochondria
    D-ribose, which is raw material for the ATP molecule
    Marine-based omega-3
    All B vitamins, including riboflavin, thiamine and B6
    Alpha-lipoic acid (ALA)
    How Metabolic Therapy Can Improve Cancer Treatment

    Seyfried is not alone in his strong belief in the metabolic origins of cancer. Dr. Abdul Slocum, a physician from Turkey, is already using this information in his clinical practice, where he treats many end-stage cancer patients. A significant number of his patients have pancreatic cancer, which has one of the worst prognoses of any cancer.

    Over 90 percent of pancreatic cancer patients die within five years. When they enter his clinic, patients are immediately placed on a ketogenic diet and remain on it throughout their treatment.

    Remarkably, Slocum is able to save many of these “hopeless” patients. What’s more, his treatment protocols are nontoxic. By harnessing your body’s ability to fight the tumor naturally, through the implementation of nutritional ketosis and other strategies, any chemotherapy agents used can be applied in the lowest possible dose. Slocum’s practice reveals the very real benefits of treating cancer as a metabolic disease.

    Support Cutting Edge Metabolic Therapies That Address the True Cause of Cancer: Defective Mitochondria

    Seyfried is conducting preclinical research at Boston College, exploring a cocktail of metabolic therapies in a metastatic mouse model, including the combination of:

    Ketogenic diet
    Oxygen therapy
    Exogenous ketones
    Glycolytic inhibitors
    Glutamine inhibitors
    Other metabolic targeting therapies
    The goal of this advanced research is to develop a nontoxic diet/drug therapeutic cocktail that can resolve both primary tumor growth and secondary tumor metastatic lesions in a range of preclinical models of cancer. For more information, you can read through his team’s paper,7 “Press-Pulse: A Novel Therapeutic Strategy for the Metabolic Management of Cancer,” published in 2017 in the journal Nutrition & Metabolism.

    To further this project, Travis Christofferson founded the nonprofit Foundation for Metabolic Cancer Therapies (formerly Single Cause Single Cure Foundation8). I encourage you to make a donation to this incredible research project, as the possibilities of it actually saving lives are far greater than most other cancer organizations, which exist solely to support the slash, poison and burn paradigm.

    I am working with Christofferson to have Seyfried’s metabolic therapies available for use as a primary intervention in a few cancer clinics and will have that information posted when they are available.

    Importantly, while other organizations will take a large percentage of your donations for administrative expenses, 100 percent of donations to Foundation for Metabolic Cancer Therapies will go to fund Seyfried’s research. You can make a tax-deductible donation online or by mailing in a check:

    Send a check of any amount made out to and mailed to The Foundation for Metabolic Cancer Therapies, 3213 West Main Street #256, Rapid City, SD 57702
    Donate online at Foundation for Metabolic Cancer Therapies. You can make a one-time donation or set up recurring contributions.
    Sources and References

    1 Cancer as a Metabolic Disease: On the Origin, Management, and Prevention of Cancer by Thomas Seyfried
    2 peterattiamd.com
    3 Nobel Prize Facts, Otto Warburg
    4 Science February 24, 1956;[phone number redacted]): 309-314 (PDF)
    5 Journal of Aging Research 2011 Article ID 807108
    6 Mercola.com, What You Really Need to Know About Your Mitochondria
    7 Nutrition & Metabolism 2017; 14: 19
    8 Foundation for Metabolic Cancer Therapies

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    Keanu Reeves Has Been Secretly Donating Millions
    posted by Danny -
    Dec 17, 2018
    As if you needed another reason to love Keanu Reeves, it turns out that he’s been running a private charity foundation for more than ten years that funds children’s hospitals and cancer research. It’s no surprise he hasn’t told anyone – the actor is known for being nicer and more humble than Hollywood stars are usually known for.

    But it’s not like he’s never mentioned it. Back in 2009, he reportedly talked about the foundation in a "Ladies Home Journal" article, explaining that he doesn’t “like my name attached to it.” “I just let the foundation do what it does,” he said at the time. Apparently, he’s motivated to give to the cause because his sister Kim was diagnosed with leukemia back in the 1990s (thankfully, it later went into remission).

    The star has also reportedly donated to other charities, like the Spinal Cord Opportunities for Rehabilitation Endowment (SCORE) charity supporting hockey players with spinal injuries. He also donated his time to help out the Stand Up to Cancer telethon in 2008, taking calls to help raise funds for the cause.

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    CancerNews posted an update

    This is another example of don't count on having your job held for you no matter what if you have cancer.

    Sinclair Broadcasting Fired a Reporter on Medical Leave for
    Cancer Treatment

    Reporter Alex George was terminated while fighting a rare bone cancer.

    Sinclair Broadcast Group doesn't have the best reputation as an employer. The company drew national attention earlier this year when it required local news stations across the country to repeat a scripted segment lifted almost directly from Donald Trump's anti-journalism talking points. And employees are trying desperately to find ways to work around Sinclair's pro-Trump programming.

    But the broadcasting behemoth isn't just content to play fast and loose with its reporters' professional reputations. It's also willing to cut them off when they're most in need. This past May on Good Morning Chattanooga, Alex George told her audience that she would be taking medical leave to focus on fighting a rare form of bone cancer. The community was reportedly very supportive, raising money, doing a charity run in George's honor, and voting the 22-year-old "best columnist/reporter" in the local paper's best-of poll. Per the Times Free Press:

    The NewsChannel 9 official Twitter account offered its own message of support: "Alex, we are so proud of you, and wish you the very best as you continue to show cancer who's boss!"

    Two months later, Alex George got a call from her supervisors at the TV station. They informed her Sinclair Broadcast Group was terminating her contract about six months early. She had been receiving disability payments while getting treatment. That immediately stopped. She no longer had a job, she was told. A company spokesperson later told the Times Free Press that Sinclair would consider exploring "possible roles for her" in the future if she wants to return.

    George told the Times Free Press that she was "shocked," adding, "I definitely wasn't expecting it. I thought the call was just going to be a check-up."

    Sinclair Broadcast Group is clearly a well-run company, with about $2.5 billion in yearly revenue.

    See the original article and a video clip from Ms. George here>> https://www.gq.com/story/sinclair-fired-reporter-cancer

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    Top 4 Cancer Screenings That Should Be on Your Radar in 2019

    Many of the lives lost to cancer each year could’ve been saved through earlier detection. Here are four screenings that should be at the top of your list in the new year.

    As the new year approaches, there’s no better time to schedule those cancer screenings your doctor has been recommending.

    According to the American Cancer Society, approximately 610,000 people were expected to die from cancer in 2018.

    But many of the lives could’ve been saved through earlier detection.

    “Cancer screening is so critical because early on in early stages of cancer there are no signs of the disease, and that is precisely when the cancer is most treatable,” Dr. Carmen Guerra, national board scientific officer of the American Cancer Society (ACS) and associate professor of medicine at the University of Pennsylvania, told Healthline.

    Guerra urges people to learn more about the guidelines from the ACS and to keep screenings for these four cancer types at the top of their list.

    1. Breast cancer
    Women ages 40 to 44 years old who are not at increased risk for breast cancer should be offered the choice to start an annual mammogram.

    “Between 45 and 54 years old, women should definitely get a mammogram every year. After 55 they can switch to every other year or continue yearly mammograms,” said Guerra.

    While there is no age maximum for a mammogram, women should discuss with their doctor what screening is best for them after age 54.

    “If their physician believes they will live for another 10 years or longer, he or she may recommend screening,” Guerra said.

    She also points out that even if you don’t have a history of breast cancer in your family, you should still follow these guidelines.

    “The truth is over 90 percent of the cases occur in people without a family history. Also, many patients tell me that they don’t feel a breast lump [during self-exams] so they don’t need screening,” Guerra said. “Mammograms detect tumors that are not able to be captured with a self-exam or even a clinician exam. Some breast cancers are the size of an eyelash. That’s what a mammography detects, something you could never feel with an exam.”

    Women who are at increased risk of breast cancer due to personal history, genetic history or because they carry a gene mutation, such as BRCA1 or BRCA2, should talk with their doctor about screening options, such as an MRI scan.

    2. Cervical cancer
    All women should begin cervical cancer screening at the age of 21.

    Between 21 and 29, screens should be conducted with a Pap smear every three years.

    Starting at age 30 and continuing all the way up to 65 years old, in addition to a Pap smear every 5 years, women should also have an HPV test.

    “We know there’s a strong link between HPV and cervical cancer,” said Guerra. “After 65, women can discontinue cervical cancer screening if their last two Pap smears over the last 10 years were normal.”

    For women who have had the HPV vaccine, Guerra says, the ACS is currently looking into whether or not screening is still needed.

    “I’m on the panel that’s looking at that question now. We don’t know yet if women will have to continue cervical cancer screening in the same way I just stated. New guidelines may come out in the next year or so and may affect the recommendations,” she said.

    Guerra also notes that the FDA has approved the HPV vaccination to be offered to people 27 to 45 years, which is an update from the approval of up to 26 years old.

    “It’s new, but hasn’t been implemented widely yet. Talk to your doctor,” she said.

    3. Lung cancer
    Lung cancer kills more people than colon, breast, and prostate cancers combined.

    Screening for lung cancer involves a low-dose CAT scan of the chest for people who are known to be at higher risk of developing the disease.

    Recommendations are to screen people (men and women) who are 55 to 74 years old, and who currently smoke or have smoked in the past, but quit in the last 15 years.

    “They have had to have smoked approximately 30 pack years or more. What that means is smoking one pack a day times 30 years or half a pack a day times 60 years,” Guerra explained.

    In addition to screening, she suggests smoking cessation counseling.

    “Smoking rates have been declining since the publication of the reports of the Surgeon General in 1964. That began to raise awareness of the harms of smoking and a lot of public health research and investment has been put into smoking cessation,” Guerra said. “We suspect that all, along with improvement in treatment, has something to do with declining rates of lung cancer.”

    4. Colon cancer
    Screening for colon cancer not only detects cancer early, but by removing polyps, which can turn into cancer, the screening can actually prevent cancer.

    “This is the only cancer screening that can do this,” Guerra said.

    Recommendations for colon cancer screening changed earlier this year.

    Previously, the ACS stated that anyone over 50 years old should start screening with colonoscopy or a stool-based test. The new guidelines lowered the age to 45 years old.

    “There is a concerning increased rate of colon cancer that we are seeing in younger individuals, even millennials, and we don’t know why. To better address this new trend, the recommendations were lowered and should continue through age 75,” said Guerra.

    Between the ages of 76 and 85, you should talk with your doctor about whether screening makes sense, and once you reach 85, screening should stop.

    Your healthcare provider will also determine how often to screen, but generally, screening is performed once every 10 years with a colonoscopy. If no polyps are found, then screening may continue in intervals of 3 or 5 years.

    For those who are concerned that colonoscopy is embarrassing or painful, Guerra says, “The truth is people who have had a colonoscopy almost universally say that the worst part is the prep, which may vary, but generally consists of a liquid you take in two portions and a clear liquid diet.”

    She adds that most people don’t remember the procedure because they receive a sedative that helps them sleep.

    “Sometimes the sedative is combined with a medicine that makes you forget things, so most people wake up and don’t think they had the colonoscopy, yet it’s over,” Guerra said.

    Is it possible to screen too much?
    Concern about over-testing and over-screening is a legit one, says Guerra. Doing so can lead to negative consequences such as time spent, cost, and in some cases harmful health effects, such as exposure to radiation (from mammograms).

    However, she says this is more reason to adhere to the guidelines.

    “For instance, the reason breast cancer screening focuses on age 45 to 54 is because if you were to plot all the cases of breast cancer that occur, it looks like a bell curve that has a peak at those years. Then it falls down,” she said. “As it falls, it’s okay to cut back on screening because the risks are also falling.”

    She adds that work needs to be done to get more doctors and patients to realize this.

    “Patients want to receive good care, and to them the yearly screening means good care, but it’s actually complex,” Guerra said. “Good care means cutting back for some people. The guidelines are based on a lot of scientific data.”

    From Healthline

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    When Support Groups Make You Feel Worse
    Support groups are meant to offer the insight of others who "get it" but for some people, they can be terrifying and depressing.

    The day I was diagnosed with a bladder condition called interstitial cystitis (IC), I joined a Facebook group called IC Warriors. There, I learned about dietary guidelines and supplements that became helpful to my recovery. I also learned how bad my condition could get. People talked about being unable to work, have sex, or function successfully day-to-day. My depression grew as I started worrying I could reach that point.

    My next experiment with support groups, after learning I had Lyme Disease, was very short-lived. One evening spent in an in-person support group left me frightened over how long Lyme can go on and how serious it can get. Several people had it for years, and one woman needed heart surgery. I didn’t come back.

    Sarah Neal Montgomery, a 27-year-old student in Georgia, has similarly mixed feelings about the IC support groups she uses on Facebook. “Seeing that there are so many people with my condition was a comfort,” she says. However, she adds, “It can be overwhelming when so many people are suffering and sharing their suicidal thoughts. I have the same depressing thoughts at times. I try to stay positive and keep those thoughts far away, but it's hard to forget about it when I see it daily.”

    Laurina Esposito, a 37-year-old CEO of a car restoration company in Los Angeles, limits her time on Lyme support groups on Facebook for similar reasons. “The negative posts can actually drain me a bit and make me worry more,” she says.

    Support groups for mental health issues can have similar problems. “There can be triggering moments where people talk about assault or something, and sometimes it stirs up a lot of emotion that I then have to deal with,” says Sarah, a 28-year-old student in Boston (who declined to share her last name so that prospective employers can’t identify her) who is a sexual assault survivor herself, of the group she attends for depression and anxiety.

    Of course, there can be lots of benefits to support groups, too. Jennifer L. FitzPatrick, a Maryland-based psychotherapist and author of Cruising Through Caregiving: Reducing The Stress of Caring For Your Loved One, says that most of her clients report positive experiences with support groups. “Experiencing a physical, mental health, or cognitive condition can make people feel like they are the only one going through it,” she says. “Friends and family who don’t have the condition can offer love but can never truly identify with the experience. Support groups offer the insight of others who ‘get it.’” They can also empower patients by giving them an opportunity to help others.

    “Support groups provide relief from overwhelming isolation associated with chronic illness,” says Ruschelle Khanna, a psychotherapist who has run outpatient mental health and substance abuse clinics in New York City. They can also help educate people about their conditions and treatment options. Terry Lynn Arnold, 60-year-old founder of the Inflammatory Breast Cancer Network Foundation who runs online support groups for people with inflammatory breast cancer, has even heard from people who were deterred from committing suicide after receiving support in groups.

    However, this type of group therapy often involves—as I experienced—the sharing of unpleasant experiences and emotions, FitzPatrick adds. Listening to these stories may provide insight into your own situation, but if they leave you feeling depressed, you have to assess whether the lessons are worth i

    Another risk of support groups is that, if not supervised by professionals, they could spread inaccurate information. “Sometimes feedback is not always appropriate or can be unsound when it is related to a medical or behavioral condition,” says social worker Caitlin Simpson, director of clinical operations at Footprints to Recovery, a network of drug and alcohol treatment centers.

    “I don't run any groups that they don't have medical people volunteering to help the group understand the science,” Arnold says. “Sometimes patients say things like ‘well, you can get that care differently than what your doctor recommends because I did and I'm fine.’ But that is an anecdotal story. That is not a scientifically based story.”

    And in online support groups especially, there’s the possibility of encountering trolls, FitzPatrick says. Even when not intended, people often end up offending people online because the tone and intention of written words can easily be misinterpreted, Arnold adds.

    To avoid these problems, Khanna recommends finding support groups with good moderators and guidelines. “Structure is needed to keep the group on task and to keep people in check when they want to focus on things other than support, such as consistent complaining or negativity,” she says. Simpson even recommends going to multiple support groups to figure out which is most conducive to your healing.

    And for the sake of your sanity, don’t assume anyone else’s situation is the same as yours. This can lead you down the rabbit hole I fell into, where you’re just waiting for every dreaded symptom other people have reported to arrive. “It's important to remember that even if someone’s experience is similar to your own, your outcome and needs may be entirely different,” Simpson says. Based on many needless freakouts, I can assure you that just because someone in your support group is in a flare today doesn’t mean you will be tomorrow.

    FitzPatrick also cautions against pushing away your loved ones just because the people in your support group understand your condition better. “While your family and friends don’t understand precisely what you’re going through, they usually know you best and love you,” she says.

    Even when support groups are structured in the healthiest way, they aren’t for everyone, Khanna says. It’s important to keep taking stock of how you’re feeling after you participate in a meeting or visit a Facebook group. “If you are in a support group and you find yourself becoming overwhelmed by sadness or always leave feeling worse than before the group, the support group may not be for you,” she adds.

    Sometimes, the solution is simply to be more thoughtful about how you use these types of groups. I’m still in several IC and Lyme support groups on Facebook, but I try to only read comments on my own posts or posts on specific topics I search for, rather than mindlessly scrolling through the page. That way, I can get the information and encouragement I need without the negativity.

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    Cognitive problems are a common side effect after chemotherapy. A new study suggests how one type of chemo may contribute.

    How does chemo brain work? One cancer drug might interfere with brain signaling

    For the millions of people treated for cancer, “chemo brain” can be an unnerving and disabling side effect. It causes memory lapses, trouble concentrating, and an all-around mental fog, which appear linked to the treatment and not the disease. Although the cognitive effects often fade after chemotherapy ends, for some people the fog persists for years, even decades. And doctors and researchers have long wondered why. Now, a new study suggests an answer in the case of one chemotherapy drug: Brain cells called microglia may orchestrate chemo brain by disrupting other cells that help maintain the brain’s communication system.

    “I can’t tell you how many patients I see who look at me when I explain [chemo brain] and say, ‘I’ve been living with this for 10 years and thought I was crazy,’” says Michelle Monje, a pediatric neuro-oncologist and neuroscientist at Stanford University in Palo Alto, California. It’s still mostly a mystery how common long-term cognitive impairment is after chemo. In one recent study by clinical neuropsychologist Sanne Schagen at the Netherlands Cancer Institute in Amsterdam, it affected 16% of breast cancer survivors 6 months after treatment.

    Monje began to probe the cognitive effects of cancer treatment in the early 2000s, starting with radiation, a therapy that can be far more debilitating than chemotherapy. A Science paper she and her colleagues published in 2003 suggested radiation affected a type of brain cell called microglia, which protect the brain against inflammation. Just like immune cells in the blood, microglia—which make up at least 10% of all brain cells—become activated during injury or infection.

    The symptoms of chemotherapy-related cognitive dysfunction pointed to abnormalities in myelin, the fatty sheath around nerve fibers that helps them transmit brain signals. More than 10 years ago, stem cell biologist Mark Noble at the University of Rochester in New York and his colleagues reported that brain cells called oligodendrocyte precursor cells (OPCs), which ultimately help form myelin, were exquisitely sensitive to chemotherapy. But later work suggested OPCs could rapidly repopulate in a healthy brain, and the long-term effects of chemotherapy on OPC cells remained mysterious.

    Monje began the new study almost 7 years ago. First, she and her colleagues examined stored brain tissue samples from children and young adults who had died from various cancers, and control patients who’d died of something else. Some had received a host of chemotherapy drugs, and some had never gotten chemotherapy. In those who’d had chemo, OPCs were markedly depleted, but only in the white matter of the brain, which is a heavily myelinated brain region. The researchers focused on a particular chemotherapy drug, methotrexate, which is especially associated with long-term cognitive problems.

    Monje’s team wanted to confirm the findings in just-donated tissue, which was offered to them by the families of two children: a 3-year-old whose brain cancer was treated with high doses of methotrexate, and a 10-year-old whose brain cancer progressed so rapidly that there was no time to administer much therapy. Again, the child who’d received methotrexate—with the last dose well over a month before he died—had a near-wipeout of OPCs in white matter. The other child did not.

    Next up for the scientists was designing a mouse model of chemo brain caused by methotrexate. The mice got the same chemotherapy treatment as the 3-year-old, adjusted for their tiny body size. The animals “have a very clear impairment in attention and short-term memory,” Monje says. The animals also had the same decrease in white matter OPCs. Studying the organ 6 months after chemotherapy ended—a long time in the life of a mouse—the researchers saw that “the myelin sheaths were thinner,” Monje says, which would disrupt brain signaling.

    The big question for Monje was whether chemotherapy was directly killing OPCs or creating an environment that was hostile to them. To answer this, her team transplanted healthy OPCs into the brains of mice previously administered methotrexate. Those healthy cells showed the same disregulation, Monje says. Typically, the brain replenishes OPCs as needed, but in the mice, it didn’t. Something in the brain’s environment was causing the cells’ decay and disappearance.

    Ultimately, the story came full circle back to the microglia that Monje had first eyed more than 15 years ago. Additional experiments on brain cells revealed methotrexate activates microglia in the brain’s white matter, causing a cascade of effects and ultimately depleting OPCs. Because several compounds that deplete microglia are in clinical trials for cancer and other indications, the scientists were able to test one of them on their chemo brain–affected animals. They found that depleting microglia was effective: It restored OPCs, normalized myelin, and rescued short-term memory, the research team reports today in Cell. That means, they write, that the microglia are likely behind chemo brain for this particular drug.

    “The authors did a great job at trying to look at this phenomenon from very different angles,” says Schagen, making sure, for example, that findings in brain tissue also held true in mice. The activation of microglia, Schagen says, looks like an “important” direct mechanism. But Schagen, who has studied the effects of several chemotherapy drugs on mouse brains, also stresses that these findings are limited to methotrexate; other chemotherapy drugs may cause cognitive problems in different ways. The dose and its timing may also affect a drug’s brain effects, Schagen says.

    Monje says there’s a lot left to do before launching a clinical trial of any potential chemo brain fighter. One question is how long any such drug must be used. Another is what molecular mechanisms are driving the brain cells to behave as they do. But she’s hopeful that, after many years of trying, she and others are moving in the right direction.

    Posted in: Brain & BehaviorHealth

    Jennifer Couzin-Frankel
    Staff Writer

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    sFrom: forbes.com

    An Israeli medical technology company is set to begin testing its new radiation cancer therapy in leading medical centers in Italy. The Alpha DaRT (Dіffusіng Alpha-emіtters Radіatіon Therapy) device delivers high-precision alpha radiation that is released when radioactive substances decay inside the tumor and kills cancer cells while sparing the surrounding healthy tissue, the company says.

    The company hopes to get approval from the European Commission by next year for the therapy.

    Early results from an ongoing pre-clinical trial on patients with squamous cell carcinoma (SCC) tumors at the Rabin Medical Center in Israel and the IRST (Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori) in Italy showed a reduction in all tumor sizes and more than 70 percent of the tumors completely disappearing within a few weeks after treatment, NoCamels reported.

    The therapy has already been tested on more than 6,000 animals and has been found “to be effective and safe for various indications, including tumors considered to be resistant to standard radiotherapy.” according to the breakthrough innovation news site NoCamels.

    Alpha Tau Medical was founded in 2016 to focus on research and development as well as commercialization of its Alpha DaRT cancer treatment. The therapy was initially developed in 2003 by Professors Itzhak Kelson and Yona Keisari at Tel Aviv University.

    According to the National Cancer Institute (NCI), cancers that are known collectively as head and neck cancers, or squamous cell carcinomas of the head and neck, usually begin in the squamous cells that line the moist, mucosal surfaces inside the head and neck (for example, inside the mouth, the nose, and the throat).

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    This is interesting and another step forward in jawn/face reconstruction

    Melbourne woman fitted with 3D printed jaw and new teeth in world first reconstruction

    A 31-year-old Melbourne woman has been fitted with a 3D printed jaw and new teeth in a world first reconstruction.

    Anelia Myburgh's face was left disfigured after surgeons removed a life-threatening cancer where she lost 80 per cent of her top jaw.

    The disfigurement left the finance worker self-conscious and uncomfortable in social situations.

    "I just want to be able to walk down the street and not have people stare, that’s my ultimate goal," Ms Myburgh told Nine News.

    She was diagnosed with cancer in April last year.

    "They removed the majority of the upper jaw, so I only have the two back teeth on each side left, they removed a portion of the lip and some under structure of the nose area," she said.

    After she was told nothing could be done Amelia did her own research and met with George Dimitroulis, a Melbourne based maxillofacial surgeon.

    A customised 3D printed jaw was developed featuring a titanium frame that could carry bone grafts, allowing teeth to be implanted.

    Skin was taken from her forearm and used it to pad out her upper lip.

    "The fact that we can 3D print a frame where we can actually anchor some teeth for her will give her back her quality of life,” says Mr Dimitroulis.

    After countless appointments, AUS$30,000 in medical bills and a five hour surgery her jaw was fixed.

    "I’m looking forward to gradually finally getting that burger."