Breaking Research News from sources other than Breastcancer.org
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HomeMom,
I had the wrong link for the last article I posted. I've fixed it now. The testing was done on TN BC using human cells and mouse models. The study identified an RNA-binding protein which was needed for the cancer cells to survive but not needed by normal cells. The next step would be to target this protein with a drug.
ETA: Here's a more detailed article that came out today: https://www.genengnews.com/news/rna-binding-protei...
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I found this article very interesting:
Seed and Soil: Tracing the Journey of Spreading Cancer Cells
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Oral paclitaxel may still be a future option despite being denied FDA approval a few months ago. "The FDA was supportive and encouraged the Company to continue development of oral paclitaxel and encequidar for the treatment of metastatic breast cancer. The FDA also agreed that a well-designed and well-conducted trial may adequately address the deficiencies raised in the CRL." https://www.obroncology.com/news/athenex-provides-update-from-fda-type-a-meeting-regarding-oral-paclitaxel?ap=334&vhid=
Interesting article LIllyishere
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this sounds interesting - early trials
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COVID Vaccine Protects Cancer Patients -- Second Dose Key
— Study reinforces need to prioritize these patients for vaccination, authors say
MedPage Today July 8, 2021
The Pfizer-BioNTech mRNA COVID-19 vaccine achieved satisfactory levels of seropositivity in patients undergoing treatment for cancer, although protection occurred later compared with a healthy population, Israeli researchers found.
Just 29% of cancer patients were seropositive after the first dose of vaccine compared with 84% of controls, with median titer scores of 42.3 and 72.0, respectively. However, the seropositivity rate climbed to 86% among cancer patients after the second dose...
"Although the immunogenicity pattern was gradual and slower than in the noncancer population, after the second dose most patients were seropositive and no documented cases of COVID-19 infection were determined," they wrote in JAMA Oncology. "Our study lends credence to the widely adopted recommendation to prioritize patients with cancer for SARS-CoV-2 vaccination."
The objective of this study was to evaluate the serologic status and safety of the Pfizer-BioNTech vaccine in patients with solid tumors who were receiving active cancer treatments.
Types of treatment included chemotherapy (58%), biologic agents (35%), and immunotherapy (36%), with some patients receiving more than one type of treatment.
... patients with breast cancer comprised 29% of the seronegative group, and 74% of these patients were treated with chemotherapy, with treatments being diverse. "Hence, we cannot assume that a specific class of drugs may hamper immunogenicity but rather that lympho-suppressive agents may induce a lack of effective seroconversion,"
Any intention to forego a second vaccine dose in some jurisdictions because of a shortage of vaccines "warrants reevaluation of unique populations, such as patients with cancer, in view of lagging immunogenicity,"
Primary Source: JAMA Oncology
Reporting: https://www.medpagetoday.com/infectiousdisease/cov...
{Access to reporting should be free but may require registration. I was also able to access the full article without charge.}
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First-Line Pertuzumab Plus Trastuzumab Plus a Taxane for HER2-Positive Locally Recurrent or Metastatic Breast Cancer
- Annals of Oncology In this multicenter, single-arm study, the authors evaluated the safety and efficacy of investigator-selected taxanes in combination with pertuzumab and trastuzumab for the management of HER2-positive, locally recurrent or metastatic breast cancer as first-line therapy. There was no difference in overall survival among taxanes, but patients treated with paclitaxel had fewer side effects compared with those treated with docetaxel or nab-paclitaxel. HR-positive disease was associated with improved outcomes; the presence of visceral disease was associated with poor outcomes.These results are consistent with the findings of the CLEOPATRA trial but expand the taxanes that can be effectively combined with trastuzumab and pertuzumab in HER2-positive breast cancer. Treatment with paclitaxel may result in less toxicity.CONCLUSIONS: Mature results from PERUSE show a safety and efficacy profile consistent with results from CLEOPATRA and median OS exceeding 5 years. Results suggest that paclitaxel is a valid alternative to docetaxel as backbone chemotherapy. Exploratory analyses suggest risk factors that could guide future trial design.
Source:Open Access Published: July 01, 2021 DOI:https://doi.org/10.1016/j.annonc.2021.06.024Reporting at: https://www.practiceupdate.com/c/120482/67/13/?els...{Access w/o charge.}0 -
great article about oligometastes and local treatment
https://ascopubs.org/doi/full/10.1200/JCO.21.00445
Oligometastases (<=5 lesions in one location) is getting more attention and guidelines.
The treatment of patients with oligometastatic disease is and must remain individualized and based on multidisciplinary decisions.
size could become part of the definition: metastatic lesions should be considered oligometastatic (ie, potentially eligible for local treatment) only when the size of the smallest lesion has reached a certain threshold, which could be proposed around 8-10 mm in diameter
Dee
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Yes, this is good news, the more they consider making this standard treatment or at least, justifiable, the better.
I am disappointed that they ruled out oligoprogressive disease rather strongly - because I wasn’t oligo at diagnosis but I was oligoprogressive/persistent with one lesion under 10mm and did have local treatment which put me back to NED. And two years later I’m still NED.
Hopefully more research can justify local treatment for small instances of progression
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Guys, from what I read and see around, de novo multiple involvement/progression in one organ might also be seen as oligo-disease, as usually these tumors, although abundant, are of a very uniform genomic setting and systemic treatments, if they work, they work for all tumors. So, this has nothing to do with local treatments, but with definitions of what oligo might be in the future. Maybe they will come up with another term too. Saulius
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So, do I understand this correctly that they are defining oligometastic by diameter of lesion rather than length?
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cowgal- If I understand the article, they are looking at the age of the tumors as represented by the tumor growth/size. The thought is if the smallest tumor is less than 8mm diameter it is not mature and there could be others lurking close by. If the smallest tumor is greater than 8mm then there is more confidence of oligometastes due to the tumor cell doubling time. Which would potentially qualify you for the local treatments. It's a bit confusing but still progress in some ways.
Olma was not in that parameter but responded. I was in that category but was refused surgery at MDACC -they insisted on a systemic working first. Can’t look back though
BSandra-good point.
Dee
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cowgal, my understanding of lesion measurement from pathology peeps is that it is the longest cross section measurement. That's how they always report right now & that oligo editorial seemed to say the same thing. It's diameter in a round lesion but since most things are not perfectly round, it's longest x section...
It's an interesting article. It is an editorial, so it's an opinion, a guidance from some experts. I imagine others will disagree with definition parameters etc. and with the recommendations as a whole.
I think the idea of waiting until a lesion is a certain size to see if others crop up or whether it truly is oligo is interesting. I also noted down the tumor doubling times - they seemed higher than I've seen in past articles but I might have just jumbled up the numbers in my head.
There was also an interesting comment about thoracotomy finding more small lesions than thoracoscopy but that although the studies on superiority of one procedure over the other hadn't given OS results yet, they thought the removal of the small ones would not be beneficial.
I can see it's a big dilemma for oncologists and oncology surgeons now. If presented with a de novo pt, how aggressively do we cut?
I think we're missing a piece of the puzzle about overall tumor burden and overall inflammation... if reducing tumor burden drastically reduces inflammation then perhaps the next mets are more controlled (both by systemic treatments and by the pts own immune system) which should yield a longer OS.
& I did not like at all the dismissal of oligoprogression for a surgical approach. Booo, raspberries at the authors.
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Moth, Dee, these articles never really explain how they define that something is oligo. What they want to say probably is that oligo-lesion is sort of in-situ metastatic tumor. But if it is not in-situ, then it is invasive, and even several mm can contribute to further spread (as also noted in the article), so I do not get the idea of "waiting". You notice a lesion that is 2 mm, and then wait until it is 8 mm, and then suddenly other 2 mm satellite lesions occur nearby because of that 8 mm lesion, and then you are like "you were curable 2 months ago but now, ups, you are incurable, sorry". Would it not be smarter to start asap with treatment of 2 mm lesion and then see if others pop-up? This way most more patients would be cured: those who are "oligo", and those who aren't "oligo" but whose tumor did not spread into surrounding environment. I never liked the "oligo" hypothesis. Too many flaws and no real criterion to define it. One of the flaws again is the denial of "oligo-progression". What if someone has achieved pCR in distant organs, and not in initial tumor (a few undetected cells left), and then initial tumor once again metastasizes with only few lesions in the beginning and they are detected? Saulius
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Sailuis- I agree. The article doesn’t make clear on definitions or parameters for treatment, but does attempt to put oligo in the spot light. I like our discussion and it makes me wonder how the professionals are viewing this article.
BTW-I had oligo progression and had SBRT to a lung met that lit up on my PET while the liver was quiet. No more progression in the lung now.
Dee
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You see, Dee, you are a real example. Now take the scenario if your lung nodule would have not been treated (I am pretty sure your lungs would have progressed more as that lesion came up being under treatment)... but it was treated and today we see that decision was absolutely correct, although according to oligo-hypothesis you did not fall into "oligo" a category and would have not qualified for local treatments. From what I read, whether lesions are 5, or 25, if the drug/local treatment works, they can be obliterated, so "oligo" (meaning "few") does not make sense, as well as waiting - not only primary tumor causes metastases but also metastatic tumors spread further, so why wait? Stage 3C (let's say it is some stage 3.5:) is curable in practice with multiple lymph node metastases and has survival rate of ~40% at 15 years, so maybe some stage 4 are also more like 3.8, and also are curable, therefore you cannot give up on any patient and curative strategies have to be in mind as much as possible. There might be a huge difference between, let's say, these two cases: case 1 - T4N3M1 with 3 genetically nonuniform metastatic lesions >1 cm in the liver, and case2 - T4N3M1 with 20 genetically uniform (for example, de novo) metastatic lesions <1 cm in the liver. Oligo theory says that case1 has more chances for a cure than case2, but actually there's no real evidence for that, as we do not know genomic arrangement of every lesion or micromet. Just remember - we usually biopsy 1 or 2, and then give treatments, and they don't work. Why? Most probably because disease is nonuniform, and remaining 3 mets have different genomic arrangement. Local treatments "do not care" of non-uniformity, and that is why they are amazing. Our immunologist said surgery lives its golden age - he said, if I recall correctly, Norwegians cyberknifed 120 metastases in one person's lung, and the person is alive and doing ok, so actually local treatment possibilities have a big future and some 20 lesions with image recognition and AI a few years ahead might be an "easy" surgery.
I also love these discussions but I think professionals would be reluctant to discuss such things - they are too afraid to be viewed as unprofessional!:) Saulius
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Saulius- you have great thought provoking points! Cyberknife(SBRT) to 120 lesions😳. They must have been tiny.
My oligo story started with 2 liver tumors both 2mm and under so I qualified for liver surgery but they would have to take the whole right lobe. My local clinic was ready to proceed but I wanted a second opinion at MDACC. They said no due to potential micrometastisis. After 4 failed systemic treatments the 2 tumors turned in to 3 in both lobes with suspect tiny lesions. They would not do SBRT to my liver at MDACC because at the time lesions (4.5cm 3cm 2.5cm) would require too much radiation. but I did get the y90 to those. Unfortunately more tumors grew in the liver but Y90 bought me time to find a systemic that would work.
my local RO only allowed a few lung lesions that are less than 3cm because of the amount of radiation involved. My lung lesion was almost 2cm. Glad it’s dead.
My current 2 larger liver lesions are heterogeneous and the larger one could use Y-90 or some other ablation to whack-a-mole it down, reduce tumor burden etc. but I am on a trial and they said no. I am going to push for it again if that tumor is wobbling in size while the other one is shrinking. Scan & plan Aug 9.
So you can see why oligo articles interest me 😉
Dee
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Great analysis, guys! Interesting discussion
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Moving Away From the Maximum Tolerated Dose
The FDA recently expressed a new commitment to testing cancer drugs at lower doses, rather than defaulting to the highest dose most people can tolerate.
CANCER DRUGS ARE ROUTINELY tested and approved for use at the maximum tolerated dose (MTD), which is defined as the highest dose most people can take without experiencing unacceptable side effects. But the MTD may not be the right dose for every cancer patient, especially if side effects and toxicity associated with cancer treatment can cause a person to stop taking the drug altogether.
To minimize the negative side effects of cancer treatment, Winer and colleagues published guidance for conducting dose de-escalation studies in the Dec. 1, 2020, Journal of Clinical Oncology. The roadmap is intended to describe how to better design and implement clinical trials to study lower drug dosages—without compromising the clinical benefit to the patient.
https://www.cancertodaymag.org/Pages/cancer-talk/M...
{No charge, and I was not required to log in, to read coverage article.}
Article contains a number of links to additional articles/coverage of the topic.
There was a report on the MBC Patient Survey at the American Society of Clinical Oncology's (ASCO's) annual worldwide meeting. You can read about it here in Medicine Matters / Oncology.
The PCDI will be talking about the results of both the Patient and Oncologists Surveys at a complimentary SHARE Cancer Support presentation on June 28, 2021 at 3PM ET, so if you're interested, please register. {No charge.}
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Dear Dee, wow, I cannot believe MDACC said no to surgery. Potential micromets, I understand, but still... crazy... Saulius
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https://news.illinois.edu/view/6367/339688859
New approach eradicates breast cancer in mice
Researchers discovered a small molecule, ErSO, that eradicates breast cancers in mice by targeting a pathway that protects cancer cells.0 -
CP418 - Wow, great article! I would love to sign up for a clinical trial.
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https://www.biospace.com/article/releases/bayer-an...
I did a quick online search for more information about the ErSO therapy that CP418 posted about, and I found the article (link above). The research team and Bayer Company have agreed to work together on this.
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Sounds very interesting but the BBC article I saw on it said that if it all goes well, it should be available in a DECADE!!! Seriously?! Why should it have to take that long when they got a vaccine for a novel coronavirus out in under a year. Why cant they move it along faster and let those with no other options to take a chance on it? the covid vaccine got an emergency approval. Couldnt they do that with a cancer treatment like this?
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I saw the BBC article on ErSO and it said that if all goes well, it will be available in a DECADE!!! Serioulsy??!! Why should it have to take that long? They got the vaccine for a novel coronavirus out in under a year. Could they give this cancer treatment an emergency approval like they did for the vaccine? Let people who have no other options take a chance at it.
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Here is a Study published November 2020 highlighting the benefits of high dose IV Vitamin C (1g/kg = 50g) twice weekly during radiation. Not to be confused with vitamin C supplements. At high IV levels, C becomes oxidative which cancer cells cannot handle. In this study, high IV-C significantly reduced NLR/systemic inflammation from radiation treatment. Enormous boost to the immune system. I had IV-C twice weekly throughout my cancer treatment, and will gladly continue it through radiation. It takes 1.5 hours while you watch a movie, nap or listen to music. I considered those my "spa days." - Esther
Observational Study J Altern Complement Med . 2020 Nov;26(11):1039-1046. doi: 10.1089/acm.2020.0138. Epub 2020 Sep 1.The Effect of High Dose Intravenous Vitamin C During Radiotherapy on Breast Cancer Patients' Neutrophil-Lymphocyte Ratio
Hyunwoo Park 1 , Jihun Kang 1 , Jongsoon Choi 1 , Somi Heo 2 , Duk-Hee Lee 2Affiliations
- PMID: 32876471
- DOI: 10.1089/acm.2020.0138
Abstract
Background: Breast cancer is very common, and the incidence is growing every year. Most breast cancers are treated with radiation after surgery. As a side effect of radiation therapy, inflammation, as well as the neutrophil-lymphocyte ratio (NLR), level increases. However, high NLR levels act as independent prognostic factors for increased mortality in all cancers. In this study, the authors investigated whether administration of vitamin C, which is effective in suppressing inflammation, may help to reduce high levels of NLR produced by radiation therapy. Methods: This study was performed retrospectively among 424 patients who were diagnosed with breast cancer and were treated with postoperative radiotherapy at Kosin University Gospel Hospital from January 2011 to December 2017. Among them, 354 patients received radiation therapy without vitamin C (the control group), and 70 experimental patients received vitamin C intravenously twice a week for at least 4 weeks during radiation therapy. The experimental group was divided into two groups according to the dose administrated: a low-dose vitamin C group (less than 1 g/kg, 52 patients) and a high-dose vitamin C group (more than 1 g/kg, 18 patients). The authors conducted three NLR measurements: before and after radiation therapy and at 3 months after radiation therapy; the authors then compared the change in NLR over time between the groups using repeated measures analysis of variance. Results: In the control group and the low-dose vitamin C-administered group, NLR was increased at the endpoint compared to before the radiotherapy, whereas NLR values in the high-dose vitamin C group were 8.4 ± 1.7, 5.9 ± 1.3, and 4.3 ± 1.5, showing a continuous decrease and a statistically significant difference (pinteraction = 0.033). These results were similarly observed in models adjusted by the patient's age and American Joint Committee on Cancer stage, with borderline significance (pinteraction = 0.065). Conclusions: Elevated NLR, a measure of systemic inflammation, has been associated with higher mortality cancer patients, including breast cancer patients. In this observational study, NLR was significantly decreased during radiation therapy in patients administered high-dose vitamin C.
Keywords: breast cancer; high-dose vitamin C; neutrophil–lymphocyte ratio; radiotherapy.
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P.S. A G6PD lab test (for G6PD deficiency which is rare) is performed before the first dose of IV Vitamin C and must be in normal in order to receive High Doses of IV Vitamin C.
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Esther I did the same. Very glad I did it too.
Did it during chemo 2 x per week. I did not do it during rads but did it again post rads along combined with HBOT (hyperbaric oxygen) which makes the C even more pro-oxidant and also helps skin healing. I loved getting it during my chemo weeks because the fluids alone were a good boost. HBOT is also *very pleasant* as long as you aren't claustrophobic. I would drift off for a great nap. HBOT literally PUSHES oxygen into your bloodstream and you leave feeling normal/ way less anemic.
People interested in getting this therapy: you will need one blood test to make sure your body can handle the high dose of C. An Integrative Med Doctor can do it as well as give the C. It's expensive (~$200 a time where I live).
My MO was not enthusiastic... No double blind clinical trial, etc. (Though tons of clinical data.)
I said, "is there any *risk* to taking high dose IV C?" His reply: "needle sticks introduce a risk of infection." Sooooo yeah, since I was already a pincushion, that was not a risk that dissuaded me. I had locally advanced TNBC and wanted to throw everything at it.
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PS my N/L ratio stayed low during treatment I think it was apx 2 or 2.5 most of the time.
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Regarding the oligo discussion, here’s a new video from Living Beyond Breast Cancer- two doctors discuss treatments and clinical trials they are doing for oligometastatic disease, what curative intent means, etc. I think at least one of them is at MD Anderson.
One thing that confused me was when they discussed size of lesions to be considered oligo - they said 5 to 7 centimeters...they must have slipped and meant to say millimeters, because 5 cm lesions aren’t “small” lesions as far as I know.
Anyway, these guys seem more conservative than the ones who wrote the article above, and they didn’t want to discuss oligo progression at all. They strictly study patients who are oligo at diagnosis. I’m not clear if they only recruit deNovo pts or if they include early stagers with spread. I’d need to watch again to have more clarity on details. The discussion of circulating tumor cell tests to detect mets, measure tumor burden etc, was interesting too.
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Olma, Dr. Tripathy is at MDA (top right in video). In my experience so far, they’ve focused on oligo de novo. When I was diagnosed in late 2016, I participated in a CTC study of blood samples but I don’t know if there’s an outcome yet. And I’m not sure about the tumor sizing but I know my bone met was 1.3x1 cm.
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Olma, thanks for sharing the link. I believe 5 cm is correct for organs, I heard this number in one of the events held by an expensive-private clinic near where I live. And also there is another category for oligo metastatic, when there are 2 or 3 locations in total 4-5 lesions, don't remember limitation of size of tumor. As the two doctors emphasized really depends on the studies' objectives the oligo metastatic term has different definitions. I really hope that they invest/ do more research on this topic.
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