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Circulating Tumor DNA Analysis to Direct Therapy in Advanced Breast Cancer
- The Lancet Oncology September 29, 2020 The investigators evaluated the ability of circulating tumor DNA (ctDNA) to accurately guide mutation-directed therapy in women with advanced breast cancer. Testing was accurate (98% sensitivity with contemporaneous tissue biopsy sequencing), and treatment in the cohorts targeting HER2 and AKT mutations with neratinib and capivasertib, respectively, reached the targeted response rate.The authors concluded that ctDNA testing has sufficient validity for adoption in routine practice.
Commentary by Lee S. Schwartzberg MD, FACP... Perhaps most significantly, plasmaMATCH carefully analyzed the concordance rates between tissue biopsies and the ctDNA plasma samples for identification of genomic alterations. The sensitivity and specificity of targeted ctDNA samples were very high, >95%, when compared with contemporaneous tissue samples. Given the ease of obtaining blood samples for ctDNA analysis, these results support the use of liquid biopsy to screen for targetable alterations in all patients with MBC. The recent FDA approval of ctDNA panels as multiplex companion diagnostics provides a potentially reimbursable means for standard-of-care usage.https://www.thelancet.com/journals/lanonc/article/...(20)30444-7/fulltext{free access to press reporting (registration may be required) and to full article.} -
Counties with Persistent Poverty Rates Experience Higher Rates of Cancer Deaths
September 30, 2020
PHILADELPHIA – Residents of counties that experience persistent poverty face a disproportionately high risk of cancer mortality, according to a study published in Cancer Epidemiology, Biomarkers & Prevention, a journal of the American Association for Cancer Research.
"To prevent health disparities, we need tools, people, and systems to ensure that everyone in this country has access to the tools they need to thrive, including socioeconomic opportunities, equity, and respect, as well as prevention resources and health care services," Moss said.
"We need interventions in these communities to change cancer-causing behaviors, to make cancer screening more accessible, to improve treatment, and to promote quality of life and survivorship," she continued. "Efforts to reduce the risk of cancer in these counties will require strategic coordination, collaboration, and funding, with input from community members every step of the way."
https://www.aacr.org/about-the-aacr/newsroom/news-...
https://cebp.aacrjournals.org/content/29/10/1949
https://cebp.aacrjournals.org/content/29/10/1949
{Free access to reporting and abstract. Free for full article.}
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'I'd love to feel a hug': Kristen Dahlgren shares one of the hardest side effects of breast cancer
NBC's Kristen Dahlgren explores a treatment that may change the way she "feels" after breast cancer.Before breast cancer, I never realized that women who have mastectomies lose feeling in their chests. It makes sense, of course — since the nerves are cut during the surgery — but it's not something that is often talked about.
....a doctor in New York City ... is doing a procedure that could change the way women feel after a mastectomy. Dr. Constance Chen, MD, a reconstructive plastic surgeon, is one of a handful of surgeons who is reconnecting nerves as part of natural tissue or '"flap" reconstruction. ... It's similar to the grafts that have been used since 2007 in arms, legs and hands.
https://www.today.com/health/kristen-dahlgren-expl...
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Shannen Doherty Is Not Signing Off Just Yet
Fighting Stage IV breast cancer has forced some self-reflection, but the '90s icon and so-called diva refuses to slow down.
This story appears in the October 2020 issue of Elle magazine.
https://www.elle.com/culture/a34144792/shannen-doh...
{Press coverage of MBC. Creation of free account required to access full article.}
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debew do these hypoxia induced proteins help to cause "stemness" of C cells, I wonder? the buggers that re-seed? Interesting!
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Santa,
It looks like hypoxia (perhaps through the protein reprogramming mechanism they identified) induces a variety of C adaptations, including increased CSCs as well as plasticity and heterogeneity. If this mechanism is behind it all, hopefully the ISRIB drug will help.
Hypoxia and Regulation of Cancer Cell Stemness: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC40432...
Role of Hypoxic Stress in Regulating Tumor Immunogenicity, Resistance and Plasticity: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC62131...
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Interesting article out from the National Cancer Institute about localized treatments for oligometastatic cancer (and an effort to re-define that term as well.) It's a call for more trials in this regard.
https://www.cancer.gov/news-events/cancer-currents...
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Bevjen, I’m in one of the trials. It’s at MDA, called EXTEND and I was randomized to radiation to my hip bone met. The spot was stable for 3 years, hopefully, rads will kill it entirely.
Thanks for sharing that 🙂
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Illimae,
I knew that you were in one of the trials, but didn't realize that it was linked to this.
I am having my second microwave ablation to a lesion in my liver (yay, local treatment!) on Oct. 19th and so even though it's not SBRT, I was happy to see an article reflecting this change in thinking. It provides some scientific basis for hope.
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Thanksfor the oligometastatic article BevJen... an interesting read for those of us with only a couple of tumours and a few nodules!
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Karen,
Good to see you popping in!
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If local treatment for oligometastatic can extend survival, then is does matter if we find mets sooner, at least in some cases, right? (Contrary to the old party line that it does not matter.)
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Makes sense to me. Good point.
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Some of the recent research is very encouraging for those who are oligometastatic and for whom the lesion can be successfully excised. It is possible that this may provide long-term control or even be curative - which is very good news; however, this is the case for a *very small* percentage of patients. Additionally, and it is my understanding that timing is critical. The stage 4 diagnosis must be made and the lesion excised before there is an opportunity for the cancer to spread to additional locations. As we know, diagnosis is often not made so timely. I think that meaningful on-going surveillance will have to be the standard of care before this happens with any regularity. It's "catch it early" part deux!
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My stage 4 Liver mets were found incidentally by a low back mri. I agree that we should get screening to catch metastasis early.
Is there a trade off between scan exposure and early diagnosis?
I think the reoccurrence numbers from some of the studies should prove we need access to scans paid by insurance, especially if we are higher risk category.
Illimae, I was offered that study but chose systemic because I had hoped to get surgical resection- gold standard. MDACC wanted to see response before they removed whole right liver lobe. Unfortunately, I am still looking for the secret sauce and the tumors grew and spread.
BTW- I did not know this, but I do not have final approval for my trial until tomorrow, either before or after the biopsy. Good thing I needed a new biopsy anyway. I start the drug on Thursday. They don’t expect any issues but could not make any promises. No wonder there is trouble getting people to participate in trials. 🤪
Dee
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Lumpie,
You raise a good point.
However, I think that awareness is the key here -- most MOs were trained when local treatment wasn't even considered. My first MO, when asked about local treatment plus systemic, told me that she had NEVER (very emphatically) recommended local treatment for what is a systemic disease. How's that for an open mind? She wouldn't even consider it.
I also think the field of interventional radiologist in particular is showing that some things are helpful to patient condition. I am NOT oligometastatic, yet my IR, who has seen all of my scans, is willing to go back in for ablation #2 on my liver. I have diffuse bone mets, too. So I think that radiologists will be key to helping cancer patients fight for additional treatments. Just my opinion.
It makes no sense to me to say that figuring out if someone is metastatic and when is irrelevant. That type of thinking needs to be questioned by all of us.
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Count me in as skeptical of the “catching progression or new mets early doesn’t matter “ line. The fact that de novo MBC cases fare somewhat better than early stage pts . who aren’t scanned and later go metastatic, seems to be evidence that letting Mets go undetected for longer periods, has an effect on outcomes. Yes de novo is “treatment naive” but still ... the logic of allowing pain, fractures and organ damage to take hold just escapes me.
Getting radsfor my single site of progression/ aka reawakened met site in my bone seemed a much better option than changing systemic treatment. Grateful it was offered and so far the wisdom of it has been borne out.
I would not have been considered oligo at diagnosis as I had more than five sites in bone.
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AlabamaD, totally understandable. In my case, I already had surgery (lumpectomy) after chemo in 2017 and my single bone met remained stable, so rads was a good fit for me. I go to MDA too and was given the option of surgery since the big studies on whether it’s helps or not we’re both flawed. So far, so good but who knows in the long term.
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BevJen, Yes - I think that local treatment is "new" though may of us wonder what took them so long. And to clarify, it is my understanding that excision is considered optimal but SRS is also very promising. I have had a few attempts at local treatment. Fortunately, my insurance agreed to pay for an attempt at ablation of a liver met - I guess that was in 2019. Many people reported to me at the time that their insurance had refused to pay for such treatment because it was deemed "experimental." I think that is a large part of the problem. Insurance gets in the way, at least in the U.S. But we also need clinical trials. Once there is decent evidence, I think insurance will be on board because, frankly, it's cheaper than the outrageous chemo prices we pay in the U.S... unless they;d just rather we die as expeditiously as possible which is also a possibility. Recent literature on radiation (SRS) is very encouraging. And I was aghast when my radiation oncologist said he thought he could get me 5 more years with CyberKnife to my liver. Nobody goes out on a limb and give numbers like that. And to someone with mets!?!? I will get my first post CyberKnife scan of liver ... probably later this month. My labs have been good and I am hoping for good news.
I posted this very encouraging article earlier this year about SRS of oligomets. Note the OS and PFS stats. They are very good.:
Stereotactic Ablative Radiotherapy for the Comprehensive Treatment of Oligometastatic Cancers: Long-Term Results of the SABR-COMET Phase II Randomized Trial
PURPOSE The oligometastatic paradigm hypothesizes that patients with a limited number of metastases may achieve long-term disease control, or even cure, if all sites of disease can be ablated. However, long-term randomized data that test this paradigm are lacking.
METHODS We enrolled patients with a controlled primary malignancy and 1-5 metastatic lesions, with all metastases amenable to stereotactic ablative radiotherapy (SABR). We stratified by the number of metastases (1-3 v 4-5) and randomized in a 1:2 ratio between palliative standard-of-care (SOC) treatments (arm 1) and SOC plus SABR (arm 2). We used a randomized phase II screening design with a primary end point of overall survival (OS), using an a of .20 (wherein P , .20 indicates a positive trial). Secondary end points included progression free survival (PFS), toxicity, and quality of life (QOL). Herein, we present long-term outcomes from the trial.
RESULTS Between 2012 and 2016, 99 patients were randomly assigned at 10 centers internationally. The most common primary tumor types were breast (n 5 18), lung (n 5 18), colorectal (n 5 18), and prostate (n 5 16). Median follow-up was 51 months. The 5-year OS rate was 17.7% in arm 1 (95% CI, 6% to 34%) versus 42.3% in arm 2 (95% CI, 28% to 56%; stratified log-rank P5.006). The 5-year PFS rate was not reached in arm 1 (3.2%; 95% CI, 0% to 14% at 4 years with last patient censored) and 17.3% in arm 2 (95% CI, 8% to 30%; P 5 .001). There were no new grade 2-5 adverse events and no differences in QOL between arms.
CONCLUSION With extended follow-up, the impact of SABR on OS was larger in magnitude than in the initial analysis and durable over time. There were no new safety signals, and SABR had no detrimental impact on QOL.
J Clin Oncol 38. Accepted on May 5, 2020 and published at ascopubs.org/journal/jco on June 2, 2020: DOI https://doi.org/10.1200/JCO.20.00818
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Me too, Olma61.
Saying finding stage IV tumors early doesn't matter to length of survival implies treating tumors early when smaller or fewer doesn't matter to length of survival.
I understand there are clinical trials that indicate that is true. But show me the oncologist who would - upon diagnosing stage 4 mets in a patient - allow that patient to postpone treatment for six months or a year because "it doesn't matter when we start treatment or how extensive the tumors are when we start treating them."
No way. It HAS to matter what the blood supplies to tumors are like and how impenetrable a tumor is. My oncologist says immature tumors are easier to eradicate than mature tumors. And it makes sense to me that the bigger the tumor load the more cancer cells there are to seed additional tumors. The data on oligomets is growing.
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My MO told me even 6 months later, the treatment would be the same. I was sad to hear this theory.
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LillyIsHere: I think the treatment would be the same - largely because that's all they've got - but the outcomes are not the same. Higher disease burden generally = worse outcomes. Not always, but usually. They don't usually mention that part.
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Dear all, the topic you discuss above is EXTREMELY important. The attitude doctors have is OUTDATED and comes from founding paradigm that stage IV is incurable. Yet, that is not true anymore, and now some patients are ALREADY cured with limited stage IV disease (or have a radiological pCR that is durable for the rest of their life = cure). Later (maybe even now) other patients with more widespread disease will be cured. So reacting earlier is PIVOTAL, and as I always say, waiting is A CRIME. I can tell you this... my wife, when first MRI results came, was suspected to have up to 2 mm wide-spread metastases in her liver, liver numbers suepr-normal. They said ,,suspicious for metastasis but must be observed in dynamics and compared to possible hemangiomas" and... waited... then in 2 weeks they re-scanned and they were up to 5 mm... then they said "uh, most probably metastases and biopsy is needed" and... waited for another 2 weeks until results came in and pathology confirmed extremely aggressive disease. Then they re-scanned again and mets were up to 8 mm, liver almost in failure (ALT, AST in hundreds), and they said "we cannot give chemo anymore because we are afraid liver can fail, so you decide whether you call it a day or try your luck". And so, with tears in our eyes we signed "we take chemo on our own risk". After that she reacted excellently to treatment, so we got lucky but boy oh boy... 12 3-weekly taxoteres... then another 6 after one year... why could they not give her THP (with primary tumor being 7 cam anyway) straight from the beginning??? Why wait for 4 more weeks to "confirm" that she is stage IV de novo? And what if the outcome would have been different? When I know how she reacted to treatment, I could tell you if they had started with THP when mets were suspected (2 mm), mets would have gone after first treatment... and maybe we could do not 12 chemos but 4 or 6 and have same result... so any MD or researcher who says that timing is not important lives "in another world". In this case, when they one day will get cancer, especially become stage IV, would they wait themselves and not go for treatment right away? I do not believe that. Saulius
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Saulius,
I couldn't agree with you more. I think that most of the oncologists that we all deal with were trained at a time when the prevailing theory was that you just watch and wait to see what develops, as with your wife. But what the heck are we watching and waiting for? Clearly it's not going to improve outcomes and it becomes a self-fulfilling prophecy. Your wife's story is a cautionary tale, but I'm sure that happens to a whole lot of people. With me, they literally could not find anything on the scans for a whole year after my tumor markers started going up. I had to ask for additional scans during that time period that still didn't show anything. Then, boom, a year later -- mets. But now that I know what I know about scans and reading of scans, I wish that I had had some of those scans in that one year time period re-read because I'll bet that a radiologist could have found something. Maybe, maybe not. But again, when my liver mets were finally seen on a CT and an MRI, when I asked about local liver treatment, my original MO said "absolutely not -- I have never recommended that in 30 years of medical practice." So as patients, we have roadblocks along the way.
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Tectonic Shift - you hit the nail on the head perfectly. Imagine being diagnosed with mets and telling your doctor “Ok doc, see ya in six months! I have a world tour coming up and I’ll start treatment when I get back!” 😂Of course they couldn’t stop us, but no way they’d be giving a blessing to that. Ditto for any Stage IV person wanting to take six months off from a treatment that keeps them stable.
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OK ....been reading here re Oligometastatic and very touched by some really passionate stories....plus a recurrent theme that MOs aren’t seemingly up to date.... is that actually the case? Are we as a group of people with a vested interest, ie living, actually best placed to comment when we don’t really know the underpinning reasoning / research behind systemic V targeted ablation treatment?
I think we are... and we deserve a clearer explaination....so what do we DO about that?
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Dee asked above, “Is there a trade off between scan exposure and early diagnosis?“ If my then oncologist had bothered to do a physical exam, to press on my upper abdomen, and ask if I had any pain there, I would have had the liver mets diagnosed a lot sooner even without a scan. Maybe even oligometastatic. Or maybe eligible for hormonal therapy. But as it was, I had numerous liver mets, some large, and had to go straight to chemo.
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I am about to have what I am told is an ablative treatment. My most recent PET showed no current activity in my bone mets (that's where my mets are so far) but a slightly enlarged periclavicular lymph node behind my left clavicle. I met with the oncology radiologist today. She seems confident (she reports that her success rate is 90% on this sort of situation) that she can blast (and completely decommission) this node with 5 stereotactic sessions. The risk, which she describes as slight, is "swelling" in that arm, which I assume would be lymphedema. She has not to date had a patient have that side effect but wanted to disclose the possibility. She was very encouraging that we may be able to keep things at bay for a while with occasional blasts in areas as needed, assuming that Xeloda continues to work. Fingers crossed that she's right. Interestingly, she was a summa cum laude graduate in chemical engineering, before she went to medical school. Smart girl.
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Lynn,
Very interesting, and I'm sure you will do well. I know that others have looked into SBRT for particular spots, and it seems that it is very well suited for that purpose. I wish you well, and it sure sounds like you are in good hands. When do you start?
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Dear Lynn, so PET showed NEW activity in that lymph node? Or is it increasing (what size is it?)? I mean how have they determined that it is malignant? People can have inflamed/increased lymph nodes for various reasons. Just curious... Sorry Lumpie for hijacking this thread - we'll be over soon...
Dear BevJen, yes, you, my Sandra, there are so many who are victims of formalities and strict protocol following. I recon they waited for a month to confirm Sandra had stage IV de novo to give her THP combo which was approved for that time for stage IV only but it was a clear mistake, as they could have started with Taxotere+Herceptin right away (as for early stage disease, because stage III was already confirmed), and then add Perjeta later. They did the same thing in CLEOPATRA for the control group. If only I had known at that time what I know now, I would have demanded treatment right away, and Sandra would have had a much lower disease burden (here we talk about 2-3 times in volume) at the start of treatment:/ This is crazy...
Saulius
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