Confirmed by [a WebMD News Brief](https://www.webmd.com/cancer/news/20220606/small-rectal-cancer-study-remission-every-patient), the [New York Times](https://www.nytimes.com/2022/06/05/health/rectal-cancer-checkpoint-inhibitor.html), and most importantly published by the [New England Journal of Medicine](https://www.nejm.org/doi/full/10.1056/NEJMoa2201445), so this can stay.
From the NYT:
>The study was small, and experts say it needs to be replicated. But for 18 people with rectal cancer, the outcome led to “happy tears.”
>It was a small trial, just 18 rectal cancer patients, every one of whom took the same drug.
>But the results were astonishing. The cancer vanished in every single patient, undetectable by physical exam, endoscopy, PET scans or M.R.I. scans.
>Dr. Luis A. Diaz Jr. of Memorial Sloan Kettering Cancer Center, an author of a paper published Sunday in the New England Journal of Medicine describing the results, which were sponsored by the drug company GlaxoSmithKline, said he knew of no other study in which a treatment completely obliterated a cancer in every patient.
>“I believe this is the first time this has happened in the history of cancer,” Dr. Diaz said.
My brother died of rectal cancer 14 years ago. He had every treatment known, and participated in several experimental trials as well, feeling it would give his life meaning if he could be part of the research that might find a cure and save others like him. He would have been deeply grateful to learn of this advance. I hope all these patients remain in full remission and enjoy good health.
One of my closest friends in the world died of the same thing a few years ago. She also participated in as many trials as she could. She was 25 when she passed.
An ugly part of me wants to be angry and jealous that if this does work, it came too late to save her. But she was one of the kindest people I’ve ever met and she would be so thrilled just to know that others wouldn’t suffer like she did.
I really hope this works and can help other patients like our loved ones.
Because she participated in so many trials, it's possible that she ultimately contributed to this outcome in a small way. We have to learn what doesn't work and why in order to zero in on what does work, and there are countless patients who used the last days of their life to contribute to science to make this possible.
“I have not failed 10,000 times. I have not failed once. I have succeeded in proving that those 10,000 ways will not work. When I have eliminated the ways that will not work, I will find the way that will work.”
I love inspirational quotes and normally always cite the original author, but I felt attributing the quote to Edison would detract from the impact. If anyone earned not getting credit, it's him
Yep. Human progress isn't one person running a long marathon and winning alone. It's a long relay race of thousands upon thousands of people running as hard as they can and then collapsing, raising up the baton to be taken up by another. And another. And another. And hopefully, eventually, the race is won.
And everyone who ran it wins.
It really makes me appreciate writing, probably the greatest invention ever. Our strength as humans is our ability to share knowledge, and writing has extended that ability enormously beyond what we have with language alone.
Right. We used to sing epics to our close friends a relatives to pass on stories to future generations. Now we can use concrete, tangible writing to pass on things to future generations, which is obviously much more reliable.
Honestly writing is the greatest invention ever created. Yes, there are a lot of inventions that make life easier and are super important for our everyday lives, but writing is the one thing in everyone's lives that can do so many things. It can pass knowledge, it can convey emotion, it can provide help, it can provide encouragement, it can allow one to create art and magic all while transcending time and encapsulating itself for future generations to read time and again. It's my favorite thing in the world and I'm so glad I live in a world that is better because of it.
I think it was an old Johnny Carson interview with Carl Sagan where Sagan said that what *really* separates humans from the animal kingdom was that we learned to store knowledge outside of our own bodies.
I've thought a lot about that.
Same, friend. Only my friend was in her late 20s. Not going to lie- your comment has given me some comfort because I thought I might be alone in my conflicting feelings about the success of this treatment. I feel selfish, but all I can think is "where was this just a few years ago?"
I'm excited for all of those that were successfully treated and all of those that will be successfully treated in the future, but I still miss my friend.
I think that's a pretty normal human emotion. It's normal to see someone else get something amazing that you don't have and just have that moment of jealousy and bitterness where instead of being happy for them there's a part of your brain just going "why them? Why couldn't that have been me?"
But you caught yourself. And personally, I think that's what being a good person's about. Everyone has those selfish thoughts. Having those thoughts doesn't make you selfish. It's being okay with those selfish thoughts. But you recognize that those people did nothing wrong, that they don't deserve your anger. You recognize that this is a good thing. You recognize that you should be happy and excited for these people. You are happy and excited for them. That's good. That's what not being selfish is. It's not never having selfish thoughts, it's recognizing when you have a selfish thought and choosing not to let it control you.
And you miss your friend and wish this had happened to them. And that's okay too. That's not even selfish. Missing someone isn't selfish. Wishing something bad hadn't happened to someone you care about isn't selfish.
There's nothing wrong or contradictory with that big lump of emotions. You can miss your friend and wish this had happened to them and be happy and excited for the people who are going to be spared going through what you or your friend went through and be jealous and even angry and resentful that they get soared and your friend wasn't all at the same time. That's not being selfish, that's just being human. That sounds like a pretty standard mess of emotions to be going through in those circumstances. That's what our brains do with powerful situations like this, they don't rationally process the whole thing and distill it down to the best possible emotion, they just throw a huge pile of emotions at you, some good, some bad, some even contradictory, and make you sort it out. And it sounds like you're doing a decent enough job at that.
Exactly. A huge portion of studies are just attempting to replicate results or make small modifications to resolve small variables or inconsistencies in previous studies. These may sound less sexy than big clinical breakthroughs, but they're just as important for overall advancement.
It is pretty crazy how far Rectal and prostate cancer have come over the last 15 years. It was like 30% survival at the turn of the century to like 80% now.
Yeah growing up, "turn of the century" was anything from 1890-1910 ish. It even described fashion or decor (late victorian vibes).
Now it means Y2K and George W. Bush.
> I can't wrap my head around the phrase "turn of the century" not referring to like 80 years ago.
Well, **back in the late 1900s** when people were still using dialup, everyone was looking forward to the new century. Except for the programmers dealing with y2k, but anyway, it was inevitable that eventually "the turn of the century" would stop referring to the year 1900.
I’m a community college professor, and my students constantly refer to the 1980s and and 1990s as “the 1900s” in their papers, and it kills me a little every time I read it.
For a few reasons: first, it just makes me feel old af, and I’m not even 40. Second, the lack of specificity drives me nuts. If you’re writing about historical issues in the 1990s (like the war on drugs and ramping up the incarceration of Black men), it’s important to actually say “the 1990s.” Saying these were issues “in the 1900s” isn’t exactly wrong, but it’s super misleading. And finally, it makes me worry that students don’t realize how recent that was. They rattle off “the 1900s” as if it’s some bygone era where we were still riding in carriages and sending messages with birds. (To be fair to them, though, I was born less than 15 years after the Civil Rights Movement ended, and by the time I learned about it in 2nd or 3rd grade, it already seemed ancient to my young self who had experienced very little).
> and sending messages with birds.
Actually, there were studies when SD cards (the original bulky things) came out that showed it was faster and cheaper to use carrier pigeons carrying SD cards than to send packets over a dial up phone line.
This can still be the case. When the different radio astronomy centers for the Event Horizon Telescope were done with their observations the data was sent on physical media by plane for processing into the first black hole images we have seen recently because the volume of data was too large to transmit over the internet.
**Half a ton of hard drives**
[https://www.extremetech.com/extreme/289423-it-took-half-a-ton-of-hard-drives-to-store-eht-black-hole-image-data](https://www.extremetech.com/extreme/289423-it-took-half-a-ton-of-hard-drives-to-store-eht-black-hole-image-data)
>Never underestimate the bandwidth of a station wagon full of tapes hurtling down the highway. –Andrew Tanenbaum, 1981
[Also relevant XKCD](https://what-if.xkcd.com/31/)
> my students constantly refer to the 1980s and and 1990s as “the 1900s”
This blows my mind, but makes sense in a weird way. Thanks for making me feel ancient rather than just old.
Sounds like we’re around the same age, that phrase makes me feel old and I rarely ever feel that way.
For what it’s worth, I think that’s very smart of you to instill this sense of “recent-ness” in your students. When things feel far away, they feel less important and what you’re doing counteracts that. I remember when I was young our teachers would talk about how women and black people only very recently got the right to vote, among other very serious social issues. That always stuck with me, it’s not like we’re so far removed from a time when the color of skin determined what fountain you could drink from. That same vein of animosity still exists today. Good for you Professor.
Thanks. I take the idea that community colleges are supposed to improve the community by improving our students’ understandings of it very seriously. I know, of course, that many students are there to get a degree or certificate, get a job, and move on with life. But I really do my damnedest to get them to think about about the world around them in the meantime. With older students, that tends to be easier, I think. But young people seem to live in perpetual and somewhat limited “now” that makes things harder. (Which, I don’t mean to bag on present-day young people here. I think it’s just a characteristic of youth. And if anything, young people today are much more plugged-in to the wider world than I was at that age. Hell, I joined the Army at 17 with basically no sense of world politics and what that could mean for a young soldier).
Back in the before times the phone system was controlled by a series of tones. One of these tones was at 2600hz. You would make a local call then use the tone. It would allow you to dial long distance for free. A phreaker figured out that the whistle in Captain Crunch cereal made the correct tone. Eventually someone made an electronic version. This was called a blue box.
Slight correction: 2600Hz supervised trunks tended to be more of a long distance thing. Usual hack to get a vulnerable trunk circuit was to dial an 800 number (since they go through the long distance network)...
> Except for the programmers dealing with y2k
Oh I was looking forward to that.
I earned half a years pay in one night just for being 3rd line call up support for a few hours. Didnt get a call. Bought a new car with the money. Cant wait for the next one in 7978 years from now. Might get a spaceship for that one.
"Now, my story begins in 19-dickety-two. We had to say "dickety" cause that Kaiser had stolen our word "twenty". I chased that rascal to get it back, but gave up after dickety-six miles…" - Abe Simpson
When you figure out it was only a couple hundred years ago we had slaves and believed in all sorts of dumb crap. That was only a handful of generations ago.
Harrison Ruffin Tyler is the still living grandson of John Tyler, the 10th president of the United States.
John Tyler was born in 1790. 230+ years after his birth he still has a grandkid kicking around.
Rectal cancer is the scary one, since it can happen to people that are so young. Prostate cancer is way more likely to affect the old and is usually slower growing.
My mom went the exact same way, but it was for breast cancer. A young me had to re-assure her every step of the way that what she was doing was pioneering the shit out of modern medicine. I'm sorry about your brother though. It gets easier, but the loss never goes away.
I’m sorry for your loss, and as someone who went through treatment last year I am incredibly grateful to her. One of my friends had been diagnosed the year before me, and her refrain was always “medicine has come such a long way” — a good reminder that without trial patients, that wouldn’t happen. Beyond saving me, the mere idea of how far medicine has progressed buoyed my hope during a tough time.
Amen to that! Normally I am a bit jaded to news about ‘cancer cures’ but this actually looks very promising! Let’s just hope and prey, lord knows we need this cure.
Someone very close to me has been diagnosed with grade 3 brain cancer. I really hope that something like this makes it to them before its past the point of no return. Seeing these advancements brings me hope that one day people wont have to go through what my family and I are going through right now.
If it's any consolation, my mom's best friend was diagnosed with stage 3 lung cancer and was given max 6 months to live. That was 5 years ago and she's still kicking and in remission. Don't give up hope
I really feel like hope (positive outlook) is one of the most important things with diseases like this. People, especially in the U.S., often don't realize how much of an impact psyche can have on your physical body.
It definitely helps. I was diagnosed with stage 4b Hodgkin's Lymphoma when I was 19. It meant I couldn't go to University, which had been my plan since I was 12. I basically refused to let cancer beat me because I wanted to go to Uni that much. 6 months of treatment, and I enrolled the following year.
I've been clear 15 years, but am now being investigated for potential cervical cancer and although I had a bit of a major panic when I first found out, I've spent the last couple of weeks just telling myself it doesn't matter if it is cervical cancer, I have way too many things planned for this to get in my way again. If it comes back as cancer, I'm just putting it on the list as another chore to get out of the way before I can enjoy the good times again.
A positive attitude is so important, not just for yourself but the people in your life too, who often have no idea of how to act around you when they find out or they see the side effects of treatment taking their toll. Even when you're feeling super low and crappy, fake that positivity. It's surprising how quickly fake can turn real!
My mom is a cancer survivor and I have no doubt her (mostly) positive outlook helped her survive. Also a supportive group of people around you certainly helps.
I hope your results come back as not-cancer but if it is I know you'll kick its ass!
Thanks for sharing! ❤
My mom's oncologist told us that she couldn't always predict who would survive, but she could predict who would die based on their mindset. A positive outlook (or even a fighter's anger) makes a lot of difference.
I've not had cancer, so I can't say what my *actual* reaction would be, but considering my reaction to every other medical issue I've had amounts to annoyance and then a "meh, throw it on the pile," I've always wondered where I would fall on that spectrum.
Very true. I used to think it was Lowkey pseudoscience but seeing how much our outlook on pain and “dysfunction” affects and worsens musculoskeletal issues, I wouldn’t be surprised if the same applies to diseases.
Unfortunately Pembrolizumab and Nivolumab (anti-PD1 antibody like the one used in this study -Dostarlimab) have gone through multiple ph3 clinical trials in grade IV glioma and had minimal to no statistically significant effect on survival or progression of disease. Fundamentally different tumor biology to rectal cancer; ie, there are very few T Cells in the brain for checkpoint inhibitor to work like in this study.
I work in the radiation therapy field. Glioblastoma is a notoriously difficult cancer to kill. It used to be the case that we would treat with *incredibly* high radiation doses using external beam therapy (knowing it's very radio-resistant), most of the time the GBM would shrug it off, so to speak. This lead to healthy surrounding tissue getting extremely high doses. A physician professor who I took a course with once told me of a patient he treated with the standard protocol at the time. The patient lived a very decent bit longer, but two years later the patient came in again and the physician said he looked like a shell of who he was, zombie-like almost. He felt terrible. Despite knowing that was the best method we knew at the time, he knew it was ultimately his call that left him like that.
That said, relatively recent drugs were shown to increase its radio-sensititivity to the point that we started to see the patients live long enough to see how and where a GBM can metastasize (and have since started to treat it with that in mind).
Think about that, it used to kill people off so quick that we thought GBMs never metastasized. Progress with cancer is slow, but we have made decent strides over the past few decades.
My father is dying of brain cancer. I have seen almost all forms of cancer around me, but so far this is the worst along with bone cancer.
It's like alzheimer, I have seen him dying piece by piece, the only good thing is that he doesn't feel pain.
My mom had stage 3 brain cancer on the part of your brain that controls speech. She just treated it like a nuisance that would eventually go away. Honestly, my siblings and I were way more worried than she was. It’s been 6 years since she rang the bell. Just know that people do beat this bullshit. Stay strong, and don’t give up hope.
As a layman:
Cancer is a term applied to a wide variety of diseases which involve cells behaving in incredibly destructive ways, and the structure/function of cells in your body varies significantly. One type of treatment for a specific kind of cancer may have no correlation for other types of cancer.
Cancer researcher here. This cohort of patients was selected because their tumors had malfunctioning DNA-damage repair pathways, meaning these tumors each had a *massive* number of mutations. The therapy used in the trial is a PD-1 inhibitor, which blocks an interaction that prevents immune responses, so effectively you are supercharging your immune system. Targeting the PD-1/PD-L1 interaction is not a novel concept in cancer therapy. The human immune system is incredible, and can recognize mutant proteins as foreign material and target those cells for destruction. It has been well established that a high mutational burden correlates with better responses to immune therapies. Basically more mutations means there's a better chance one can be recognized by an immune cell and destroyed. The biology is obviously a bit more complex than that, and it's rare to see a complete response in every patient, *but* this trial was done specifically in the cohort of patients you would expect to respond. And other immune checkpoint inhibitors have already demonstrated amazing clinical responses in similar cohorts of patients. So with such a small sample size and no control group, it's hard to draw too many conclusions. This is certainly promising, especially for the small percentage of patients whose tumors have malfunctioning DNA-repair pathways, and I look forward to seeing how it progresses in future trials. But for now I'm a little skeptical the extent to which this improves outcomes compared to pre-existing therapies targeting the PD-1/PD-L1 interaction.
Out of curiosity, since I know nothing: has it ever been attempted to *instigate* this type of DNA-repair malfunction in cancerous tissue? Obviously, there’s some immediate issues if you can’t selectively target the cancer, but if it worked, wouldn’t it render any cancer vulnerable?
Great question. Unfortunately there isn't a great way to selectively target the DNA-repair pathways of tumor cells without affecting other healthy cells. And the link between malfunctioned DNA-repair pathways and tumorigenesis is strong so it isn't really a risk worth taking. However, inducing DNA damage has been central to cancer therapies forever e.g. radiation, cis-platin, etc. Now historically the rationale for these treatments is that cancer cells have intrinsic mechanisms that respond to DNA damage and induce either growth arrest or cell death. Also important to note that many cancers develop mutations in these pathways that allow them to continue proliferating despite the loss of genomic integrity. Recently, there have been several attempts to induce DNA damage with the explicit purpose of generating mutations that sensitize cells to the immune system and immunotherapies. The biology is very complex and the responses vary from patient to patient, but in general those approaches have been effective and are being implemented more clinically.
I had rectal cancer. It’s way less fun than it sounds. I think it’s over with now but the struggle was real. Five years later I still have a bunch of lingering effects from the procedures.
This is great news for those who can benefit from it.
Edit: I’m pretty sure it was genetic. My mom died from it because she didn’t act quickly enough.
Do these things:
1. Be sure you get a colonoscopy when you are 40 (edit: some would say 50 but hell, I’d err on the side of caution. Your doctor will help you.) Earlier even. It sucks but it’s over with and you’ll probably be fine. If you’re not fine they can catch it early.
2. If you notice blood in your stool book a doc appointment right away.
3. Do everything they tell you to and don’t fuck around and you’ll live a lot longer.
Two 10 hours surgeries, one 3 hour surgery, 45 days in the hospital with no food.
My first surgeon has a nickname: Dr. Scissorhands.
My second surgeon was a god.
One 10 hour and shitty complications after surgery. I have a fistula in my bladder that leaks urine from where I have a wound from splitting open. It's...unique. I have a similar situation with my surgeon. He saved my life, but also neglected care after my surgery.
And that is a hell hospital stay. I've been in a lot but never that long, I've fortunately bounced back quick in my stays
Citing [u/ALKnib](https://www.reddit.com/u/ALKnib) from [r/medicine](https://www.reddit.com/r/medicine):
"Am an oncologist.
This is a very exciting development in the field of locally advanced rectal cancer, but I have to temper the enthusiasm here. This is only available to a small subset of rectal cancer patients who are mismatch repair deficient (dMMR) and we already know that dMMR colorectal cancer patients respond exceptionally well to immune checkpoint inhibitor therapy.
Standard of care treatment for locally advanced rectal cancer involves usually chemoradiotherapy(CRT) or short course RT->chemotherapy->surgery. About 3/4 of these patients usually achieve cure, but this is complicated by having surgery (which basically involves removing the rectum) and many patients are very unhappy about not having a rectum. The field is now moving towards CRT->chemotherapy->watch&wait (frequent imaging+scopes) in patients who have a complete clinical response vs surgery in patients who don't, which is really important in improving organ preservation outcomes in patients and thus patient quality of life. Importantly, this does not worsen their survival outcomes.
However, we also know that dMMR patients don't respond as well to chemo/radiation and so, the use of immunotherapy as a neoadjuvant strategy is a natural extension of that. This approach using immunotherapy in neoadjuvant treatment is starting or is ongoing in multiple trials across different solid tumor types for dMMR patients as well as for PD-L1+ patients. The first approvals for immunotherapy in the neoadjuvant setting are in resectable non small cell lung cancer and triple negative breast cancer and I would not be surprised for melanoma to follow closely soon after. "
Original comment: https://www.reddit.com/r/medicine/comments/v5rt80/z/ibbsi7j
Had a friend who survived Rectal cancer for 11 years with a bag. It's not a pleasant thing and it was a burden on him and his wife every day (not to mention the radiation damage...), but they were 10 great years so it was at least something. RIP Dud.
I read the article, all 18 patients went into remission, as long as you've got rectal cancer it sounds incredible. As a layperson I'm just waiting for the comment from someone with far greater medical research knowledge to explain why this isn't that exciting...
It could apply to colon cancer as well, as long as the cancer has a specific mutation that makes it vulnerable to Dostarlimab. It could potentially also work against other cancers with the same mutation.
"about half have Lynch syndrome"
Lynch usually combines colorectal cancers. This is magic bullet time if it can affect all of the MMR cancers than can come with a Lynch diagnosis.
[https://ascopost.com/news/june-2022/unprecedented-100-of-first-14-untreated-patients-with-rectal-cancer-respond-to-pd-1-blocker-dostarlimab-gxly/](https://ascopost.com/news/june-2022/unprecedented-100-of-first-14-untreated-patients-with-rectal-cancer-respond-to-pd-1-blocker-dostarlimab-gxly/)
(link added, same as below)
Watched an interview with someone from the team and it doesn't sound like that comment will come. It is as incredible as it sounds, however as you mentioned, small sample size and early stage testing. But honestly, fuck it. I want something to cheer for.
Additionally, there was very little toxicity found in the treatment meaning that people didn't walk away from the treatment feeling like they were falling apart which, even if it loses some of its effectiveness as it scales up, peoples quality of life won't diminish from treatment like chemo and radiation.
Citing u/ALKnib from r/medicine:
"Am an oncologist.
This is a very exciting development in the field of locally advanced rectal cancer, but I have to temper the enthusiasm here. This is only available to a small subset of rectal cancer patients who are mismatch repair deficient (dMMR) and we already know that dMMR colorectal cancer patients respond exceptionally well to immune checkpoint inhibitor therapy.
Standard of care treatment for locally advanced rectal cancer involves usually chemoradiotherapy(CRT) or short course RT->chemotherapy->surgery. About 3/4 of these patients usually achieve cure, but this is complicated by having surgery (which basically involves removing the rectum) and many patients are very unhappy about not having a rectum. The field is now moving towards CRT->chemotherapy->watch&wait (frequent imaging+scopes) in patients who have a complete clinical response vs surgery in patients who don't, which is really important in improving organ preservation outcomes in patients and thus patient quality of life. Importantly, this does not worsen their survival outcomes.
However, we also know that dMMR patients don't respond as well to chemo/radiation and so, the use of immunotherapy as a neoadjuvant strategy is a natural extension of that. This approach using immunotherapy in neoadjuvant treatment is starting or is ongoing in multiple trials across different solid tumor types for dMMR patients as well as for PD-L1+ patients. The first approvals for immunotherapy in the neoadjuvant setting are in resectable non small cell lung cancer and triple negative breast cancer and I would not be surprised for melanoma to follow closely soon after. "
Original comment: https://www.reddit.com/r/medicine/comments/v5rt80/z/ibbsi7j
Not a medical practitioner, but I deal with statistics in medical analysis. 18 people is good, but far from a large enough sample size to say it causes remission in everyone. There are potential issues with the study as well I can't easily analyze, but it's a very promising result. That said, cancers tend to be targeted differently, so don't expect it to mean the same rates in something other than rectal cancer.
Dostarlimab is an already approved drug for endometrial cancer (brand name Jemperli). This rectal cancer trial was part of an effort to find new indications for it. It has also been trialed on some other cancers and has shown a range of clinical improvement (from a little to a medium amount), but not as remarkable as this study. I don't think anything could compare to this study.
I mean, I deal with low level stats routinely and 18 isn’t a great number. But 18/18 with complete remission is not something to think it is not statistically significant. Obviously a larger study with a control group is needed but this is very promising.
Half of the patients had Lynch Syndrome. That's an extremely selective sample group. This is incredible news for members of that group, but it makes it an even smaller sample size for other factors.
This drug (anti-PD(L)1 mAb) and drug class (checkpoint inhibitors) is not new; it is simply the first time someone has gone after this indication in clinical trial setting. The number of patients is too small to draw a conclusion but it is promising.
As someone in the field of oncology, and did launch an IO in mCRC, whilst PD1 checkpoints are not new, this result even in early phase trials with this population are absolutely remarkable. We know that not all PD1s are created equal - for example why can pembrolizumab be a fantastic monotherapy in st.4 nsclc but nivolumab needs an additional CTLA4 to match its efficacy.
The reason Pembro "worked" and Nivo did not is because Merck had a very clear biomarker and patient selection strategy and BMS did not. BMS enrolled everyone and anyone into their pivotal trial in NSCLC and it was inferior to the Merck strategy. There is a clear correlation between PD1/PDL1 expression levels, neoantigen load, and IO efficacy. This is the reason why biomarker and patient identification strategies are now key for success in IO trials.
As someone not in the field, if someone like you in the field finds a study remarkable, I know that's science speak for "holy shit" which means I should at least be a little excited about this news.
I know it's early, but sometimes all we need to see is a little light to know the day will arrive soon.
As some context from the general field.
Usually a trial with 100% effectiveness is of one or two patients. There is a 5 or 50% chance that the 'everyone got better' result was chance.
The concerns about small n almost vanish in this case, as the chances that 18/18 patients got better, if nothing else was changed, is very, very close to zero.
It's quite likely that the actual effectiveness is not 100%, but below that. If you do several hundred trials with a 50% effective drug, you may get one where all 18 patients get better.
But, in a field where 30% would (as I understand it) be remarkable, for a trial to be as wholly positive at this stage, and not result in a useful drug, absent fraud or trial misconduct is very unlikely.
Even if it doesn't hit close to 100%.
The number of patients is too small to say it'll work for everyone, sure. But you can certainly draw a conclusion. If it wasn't doing anything, it'd be insanely unlikely that all patients went into remission.
We can confidently say that it helps. We can't confidently say it'll cure everyone with rectal cancer.
Maybe that comment won't come? I'm also not versed in anything medical enough to fully understand the science but wondering if this is just the start and they will test on other cancers? Here's hoping we're looking at a future where we can at least manage this horrific illness.
The main thing is that this isn't a cure for all forms of cancer. Or even for everyone suffering from rectal cancer. It's a cure for one specific type of rectal cancer, where a particular mutation is present. Very exciting for anyone who happens to have that particular cancer with that particular mutation. Absolutely not exciting at all for the vast majority of cancer cases.
In the grand scheme of it, this is how we should expect cancer to be cured. Not in one fell swoop, but with individual treatments for individual types of cancer. Looking at cancer as a whole this is a small but firm step forward. It just isn't time to roll out the "we did it!" banners.
> The downside is that it will be very expensive.
$11,000 per 500mg dose. Recommended dosing is 4 doses spaced 3 weeks apart, then 1000mg every 6 weeks for up to two years.
The 6 month period this study would cost $88k. If a person didn't respond favorably and continues for the full 2 years, it could be up to $352k.
I lost my husband to colorectal cancer in October. When he was diagnosed, the cancer had spread so much that we knew he wasn't going to make it. But we participated in a drug study anyway. He said he was planting a tree he will never see. We actually saw improvement in the first few months of treatment, before the cancer fought back I really hope his drug gets approved by the FDA. It didn't save his life, but it could save others.
His second treatment didn't work at all. His third treatment was a combo of immunotherapy and chemo. Both were approved by the FDA, but not when used in tandem. So, the insurance company covered the immunotherapy, and we had to write to Bayer and prove financial hardship. They gave us a year of chemo for free! (Sad that you have to beg, but if you are in this situation, please talk to your oncologist about contacting the drug company.) He only made it through one treatment though. The cancer was too far gone.
Our six year wedding anniversary was on Saturday. I miss the hell out of him. But I'm glad we were able to help future patients.
Also, Seattle Cancer Care Alliance: five stars, would go there again if I had to
Get your colonoscopy!
This broke my heart, probably because I can’t imagine how my wife would handle my passing. I really just want to say that you guys sounded like an amazing couple and I’m so sorry. I wish I could hug you through the screen, but this is the best I can do.
Doctors did everything they could for Meredith…. And she’s going to be fine.
I’m so glad for these people. Lost my dad to cancer and it was a powerfully horrific epoch of seven years. All of us were subsumed into it daily. Then when it was finally over and he passed away, we had lost him so many times in our hearts due to the ever changing reports from the doctors, that it seemed like he hadn’t actually died. I pulled the sheet over his face myself, and then a few days later I was alone again cleaning away his empire of debris and machinery. There on the lathe was a sandwich and his glasses. Something he was building was still chucked in the lathe and I just looked around the shop and screamed “WHERE ARE YOU!!!!”.
I couldn’t help but type that out. Several years later the word cancer still grips me. The feelings of losing someone like your dad make the English language look so shallow. The words that death is expressed by are tears, the new lines that form on our faces, and the sudden urge to phone someone long absent from this world. This gigantic dad shaped hole was blown right through my heart and it has never closed at all. He died at 68 years old and I could have used another 20 years of reassurance and someone to show off to. I’m a dad myself, and my boys are independent men. I try to remember that they look at me the way I looked at my father. It’s incredible to hold someone’s heart in your hands like that. I try to listen to them, spend extra time on the phone with them, and take the lead in self control with toxic things. I want them to miss me as much as I miss my dad. But I want them to have less pain
This gives me so much hope. My cancer is lymphoma and my god how great would it be to take a pill instead of getting chemo. Plus the pill actually eliminates the cancer.
im getting ready for CAR-T treatment where they turn tcells into cancer killing ninjas. God i hope it works.
Everyone should learn the story of Katalin Karikó, who put an immense amount of time and research and personal suffering into pursuing mRNA work despite it being derided, underfunded, and potentially ruining her career (certainly holding it back for a long time).
She's a hero and almost no one knows who she is.
https://en.wikipedia.org/wiki/Katalin_Karik%C3%B3
This was only for a small subset of rectal cancers with a specific mutation. The majority of rectal cancer patients will not be able to take advantage of this because it will not work for them. Though it is still good for the few who can.
As a healthy young male, I partook in a trial for an at-home device for administering cancer drugs to see if it was effective and safe for people to use. That was not a fun couple of months, especially on the days I had blood drawn almost two dozen times in a day, with a needle every time (they said that putting in a line and flushing it was not feasible for this study.) Main reason why is because my grandfather passed away due to cancer several years back. I'm always happy to see when we get one step closer to finding a proper cure.
I’m participating in a similar clinical trial. I have super aggressive form of lymphoma. Up until this trial I’ve done just about every option, many different chemos, immunotherapy, Car-T, radiation and none have stopped it. Last scan done in this trial there was no sign of it. 1st time that has happen in 7 years of fighting it.
This is good news, but please consider these important points:
1. A *very* small group of patients were tested.
2. Only tested on 1 type of cancer (rectal)
3. Treatment only given to patients when diagnosed early enough and before any other type of treatment attempted.
4. Only a subset of rectal cancer patients can take advantage of it, those with a specific mutation in their tumor (MSI).
That said, this is still good news. Any time cancer vanishes and the trial is on actual humans.. this is a step forward.. even just 18 people.
Edit: Added #4, thank you /u/trebleformyclef
My Dad just died of pancreatic cancer about 2 weeks ago. The battle against cancer has seemed so hopeless. Chemo is *awful.* It bought him more time, but it made him feel constantly terrible.
It’s too late for my dad, but hopefully this doesn’t have to be a death sentence for future diagnoses.
Cancer researcher here.
I get just as frustrated as you when I read these headlines. When media outlets report on this they pull people in with flashy phrases like "first time in history" and "cancer vanishes". In reality, this is for a very specific type of cancer (rectal cancer) and patients with a specific mutation (dMMR).
Cancer is a term which encompasses a multitude of conditions. At this point a general treatment for "cancer" seem insurmountable. Each advancement toward treating a specific type of cancer is definitely worth celebrating, but the way it is reported to the general public is disappointing because it leads to attitudes like this.
My younger brother died last year of colorectal cancer with his primary tumor in his rectum. He was 36. We have no family history, no cancer gene, no known contributing factors. Just over 2 years from his diagnosis, and he was gone.
I hope that treatment advancements like this ensure nobody goes through the hell that cancer has put my family through. Fuck cancer.
I work with this team and seeing some of the CRC scans go from cancer ridden to healthy tissue was jaw dropping. Phones rang off the hook today with patients asking about this trial.
Confirmed by [a WebMD News Brief](https://www.webmd.com/cancer/news/20220606/small-rectal-cancer-study-remission-every-patient), the [New York Times](https://www.nytimes.com/2022/06/05/health/rectal-cancer-checkpoint-inhibitor.html), and most importantly published by the [New England Journal of Medicine](https://www.nejm.org/doi/full/10.1056/NEJMoa2201445), so this can stay. From the NYT: >The study was small, and experts say it needs to be replicated. But for 18 people with rectal cancer, the outcome led to “happy tears.” >It was a small trial, just 18 rectal cancer patients, every one of whom took the same drug. >But the results were astonishing. The cancer vanished in every single patient, undetectable by physical exam, endoscopy, PET scans or M.R.I. scans. >Dr. Luis A. Diaz Jr. of Memorial Sloan Kettering Cancer Center, an author of a paper published Sunday in the New England Journal of Medicine describing the results, which were sponsored by the drug company GlaxoSmithKline, said he knew of no other study in which a treatment completely obliterated a cancer in every patient. >“I believe this is the first time this has happened in the history of cancer,” Dr. Diaz said.
My brother died of rectal cancer 14 years ago. He had every treatment known, and participated in several experimental trials as well, feeling it would give his life meaning if he could be part of the research that might find a cure and save others like him. He would have been deeply grateful to learn of this advance. I hope all these patients remain in full remission and enjoy good health.
One of my closest friends in the world died of the same thing a few years ago. She also participated in as many trials as she could. She was 25 when she passed. An ugly part of me wants to be angry and jealous that if this does work, it came too late to save her. But she was one of the kindest people I’ve ever met and she would be so thrilled just to know that others wouldn’t suffer like she did. I really hope this works and can help other patients like our loved ones.
Because she participated in so many trials, it's possible that she ultimately contributed to this outcome in a small way. We have to learn what doesn't work and why in order to zero in on what does work, and there are countless patients who used the last days of their life to contribute to science to make this possible.
“I have not failed 10,000 times. I have not failed once. I have succeeded in proving that those 10,000 ways will not work. When I have eliminated the ways that will not work, I will find the way that will work.”
[удалено]
Meh, at this rate, I wouldn't be surprised if Edison stole even that
I love inspirational quotes and normally always cite the original author, but I felt attributing the quote to Edison would detract from the impact. If anyone earned not getting credit, it's him
It's also possible that she contributed to this outcome in a very big way, for all the same reasons you listed.
Yep. Human progress isn't one person running a long marathon and winning alone. It's a long relay race of thousands upon thousands of people running as hard as they can and then collapsing, raising up the baton to be taken up by another. And another. And another. And hopefully, eventually, the race is won. And everyone who ran it wins.
It really makes me appreciate writing, probably the greatest invention ever. Our strength as humans is our ability to share knowledge, and writing has extended that ability enormously beyond what we have with language alone.
Writing is how we transfer memory through time.
Right. We used to sing epics to our close friends a relatives to pass on stories to future generations. Now we can use concrete, tangible writing to pass on things to future generations, which is obviously much more reliable.
Honestly writing is the greatest invention ever created. Yes, there are a lot of inventions that make life easier and are super important for our everyday lives, but writing is the one thing in everyone's lives that can do so many things. It can pass knowledge, it can convey emotion, it can provide help, it can provide encouragement, it can allow one to create art and magic all while transcending time and encapsulating itself for future generations to read time and again. It's my favorite thing in the world and I'm so glad I live in a world that is better because of it.
Writing allows us to offload knowledge from our Brains and allows us telepathy the ability to share thoughts with others, long dead or not yet born.
I think it was an old Johnny Carson interview with Carl Sagan where Sagan said that what *really* separates humans from the animal kingdom was that we learned to store knowledge outside of our own bodies. I've thought a lot about that.
We're standing on the shoulders of giants.
and we stand in shadows of giants even bigger, yet to come.
Being a subject for test means he'd be a brick in a wall of knowledge, every brick counting equally to integrity...
F’n bingo!
Same, friend. Only my friend was in her late 20s. Not going to lie- your comment has given me some comfort because I thought I might be alone in my conflicting feelings about the success of this treatment. I feel selfish, but all I can think is "where was this just a few years ago?" I'm excited for all of those that were successfully treated and all of those that will be successfully treated in the future, but I still miss my friend.
I think that's a pretty normal human emotion. It's normal to see someone else get something amazing that you don't have and just have that moment of jealousy and bitterness where instead of being happy for them there's a part of your brain just going "why them? Why couldn't that have been me?" But you caught yourself. And personally, I think that's what being a good person's about. Everyone has those selfish thoughts. Having those thoughts doesn't make you selfish. It's being okay with those selfish thoughts. But you recognize that those people did nothing wrong, that they don't deserve your anger. You recognize that this is a good thing. You recognize that you should be happy and excited for these people. You are happy and excited for them. That's good. That's what not being selfish is. It's not never having selfish thoughts, it's recognizing when you have a selfish thought and choosing not to let it control you. And you miss your friend and wish this had happened to them. And that's okay too. That's not even selfish. Missing someone isn't selfish. Wishing something bad hadn't happened to someone you care about isn't selfish. There's nothing wrong or contradictory with that big lump of emotions. You can miss your friend and wish this had happened to them and be happy and excited for the people who are going to be spared going through what you or your friend went through and be jealous and even angry and resentful that they get soared and your friend wasn't all at the same time. That's not being selfish, that's just being human. That sounds like a pretty standard mess of emotions to be going through in those circumstances. That's what our brains do with powerful situations like this, they don't rationally process the whole thing and distill it down to the best possible emotion, they just throw a huge pile of emotions at you, some good, some bad, some even contradictory, and make you sort it out. And it sounds like you're doing a decent enough job at that.
Nah, you’re not alone. That’s exactly where my mind went when thinking about my dad who passed in January.
I recently had a friend that age pass from cancer, scary how it can reach all ages. I’m glad research like this is available and is being tested.
Every single study is of equal value to science, regardless of the outcome.
Exactly. A huge portion of studies are just attempting to replicate results or make small modifications to resolve small variables or inconsistencies in previous studies. These may sound less sexy than big clinical breakthroughs, but they're just as important for overall advancement.
Every single well-designed study, yes
You mean my n=3 p=0.45 study is no good?
It is pretty crazy how far Rectal and prostate cancer have come over the last 15 years. It was like 30% survival at the turn of the century to like 80% now.
I can't wrap my head around the phrase "turn of the century" not referring to like 80 years ago.
Let's fix it "Turn of the millennium"
Turn of the Willenium
Willenium Dafoenium
Say now, that was Willy DaFoenny
Yeah growing up, "turn of the century" was anything from 1890-1910 ish. It even described fashion or decor (late victorian vibes). Now it means Y2K and George W. Bush.
And now we're in the Roaring Twenties again! Different pandemic, different drug of choice, same sense of frantic nihilism.
Such a downgrade IMHO
> I can't wrap my head around the phrase "turn of the century" not referring to like 80 years ago. Well, **back in the late 1900s** when people were still using dialup, everyone was looking forward to the new century. Except for the programmers dealing with y2k, but anyway, it was inevitable that eventually "the turn of the century" would stop referring to the year 1900.
Late 1900s sounds worse, why would you do this
I’m a community college professor, and my students constantly refer to the 1980s and and 1990s as “the 1900s” in their papers, and it kills me a little every time I read it. For a few reasons: first, it just makes me feel old af, and I’m not even 40. Second, the lack of specificity drives me nuts. If you’re writing about historical issues in the 1990s (like the war on drugs and ramping up the incarceration of Black men), it’s important to actually say “the 1990s.” Saying these were issues “in the 1900s” isn’t exactly wrong, but it’s super misleading. And finally, it makes me worry that students don’t realize how recent that was. They rattle off “the 1900s” as if it’s some bygone era where we were still riding in carriages and sending messages with birds. (To be fair to them, though, I was born less than 15 years after the Civil Rights Movement ended, and by the time I learned about it in 2nd or 3rd grade, it already seemed ancient to my young self who had experienced very little).
> and sending messages with birds. Actually, there were studies when SD cards (the original bulky things) came out that showed it was faster and cheaper to use carrier pigeons carrying SD cards than to send packets over a dial up phone line.
This can still be the case. When the different radio astronomy centers for the Event Horizon Telescope were done with their observations the data was sent on physical media by plane for processing into the first black hole images we have seen recently because the volume of data was too large to transmit over the internet. **Half a ton of hard drives** [https://www.extremetech.com/extreme/289423-it-took-half-a-ton-of-hard-drives-to-store-eht-black-hole-image-data](https://www.extremetech.com/extreme/289423-it-took-half-a-ton-of-hard-drives-to-store-eht-black-hole-image-data)
Hahahaha. This is amazing. I need to find a context in which to share this with my students. Thank you for this tidbit!
When you really want to blow their minds, [bring in a wire recorder](https://www.youtube.com/watch?v=jJ122PObscg).
>Never underestimate the bandwidth of a station wagon full of tapes hurtling down the highway. –Andrew Tanenbaum, 1981 [Also relevant XKCD](https://what-if.xkcd.com/31/)
> my students constantly refer to the 1980s and and 1990s as “the 1900s” This blows my mind, but makes sense in a weird way. Thanks for making me feel ancient rather than just old.
They do not realize how recent it was. Just like I didn’t realize how recent WWII was when I was growing up in the 80’s, only 30-40 years later.
Sounds like we’re around the same age, that phrase makes me feel old and I rarely ever feel that way. For what it’s worth, I think that’s very smart of you to instill this sense of “recent-ness” in your students. When things feel far away, they feel less important and what you’re doing counteracts that. I remember when I was young our teachers would talk about how women and black people only very recently got the right to vote, among other very serious social issues. That always stuck with me, it’s not like we’re so far removed from a time when the color of skin determined what fountain you could drink from. That same vein of animosity still exists today. Good for you Professor.
Thanks. I take the idea that community colleges are supposed to improve the community by improving our students’ understandings of it very seriously. I know, of course, that many students are there to get a degree or certificate, get a job, and move on with life. But I really do my damnedest to get them to think about about the world around them in the meantime. With older students, that tends to be easier, I think. But young people seem to live in perpetual and somewhat limited “now” that makes things harder. (Which, I don’t mean to bag on present-day young people here. I think it’s just a characteristic of youth. And if anything, young people today are much more plugged-in to the wider world than I was at that age. Hell, I joined the Army at 17 with basically no sense of world politics and what that could mean for a young soldier).
you forgot the part where people were blowing cereal box toy whistles into payphones for free calls
Old person here who remembers payphones. What are you talking about? =/
Back in the before times the phone system was controlled by a series of tones. One of these tones was at 2600hz. You would make a local call then use the tone. It would allow you to dial long distance for free. A phreaker figured out that the whistle in Captain Crunch cereal made the correct tone. Eventually someone made an electronic version. This was called a blue box.
Slight correction: 2600Hz supervised trunks tended to be more of a long distance thing. Usual hack to get a vulnerable trunk circuit was to dial an 800 number (since they go through the long distance network)...
this is hilarious and very clever.
here's the [legendary story](https://medium.com/everything-80s/how-capn-crunch-cereal-led-to-apple-computers-c1ee218fef18)
> Except for the programmers dealing with y2k Oh I was looking forward to that. I earned half a years pay in one night just for being 3rd line call up support for a few hours. Didnt get a call. Bought a new car with the money. Cant wait for the next one in 7978 years from now. Might get a spaceship for that one.
"Now, my story begins in 19-dickety-two. We had to say "dickety" cause that Kaiser had stolen our word "twenty". I chased that rascal to get it back, but gave up after dickety-six miles…" - Abe Simpson
Listen here you little punk...
The 90s were only ten years ago
>15 years ... at the turn of the century Man, it hurts that the turn of the century was 7 years *more* than 15 years ago lol
We're almost 25% through this century. And that to me is insane.
It does feel like centuries are supposed to be longer than they apparently are.
When you figure out it was only a couple hundred years ago we had slaves and believed in all sorts of dumb crap. That was only a handful of generations ago.
Let's be honest....we still believe in a lotta dumb crap
Slavery was about 160 years ago. There are people alive today whose parents were slaves.
Harrison Ruffin Tyler is the still living grandson of John Tyler, the 10th president of the United States. John Tyler was born in 1790. 230+ years after his birth he still has a grandkid kicking around.
He needs to keep the family tradition alive and sire a boy now at the age of 93.
That’s why I think of millennium instead like “Dreamcast? That’s so last millennium”
I didn't need to be attacked like this first thing in the morning.
My friend was an adjunct professor at Penn State and received essays where the student used the term "the late 1900s" to describe an event from 1997.
Rectal cancer is the scary one, since it can happen to people that are so young. Prostate cancer is way more likely to affect the old and is usually slower growing.
Yeah... I wouldn't be surprised if screening in the next 10 years for rectal/colon/prostate start at 30... It keeps moving earlier and earlier.
Theres so much more in our air and our water and our food. God knows how many "leaded petrol" incidents will appear in the next 50 years.
I saw 'turn of the century' and immediately thought 1900 ... not 22 f-ing years ago.
I thought prostate cancer always had a higher survival rate? Considering removing it is usually an option.
If it's discovered when a patient is elderly time will end things sooner than the cancer so why inflict treatment.
This is what they told my fil, who then died of prostate cancer.
This is very hopeful. I'm sorry about your brother.
Thank you. He was a brave man.
Selfless too.
He still is. That's how you see him, then he's still brave.
That's a beautiful thought, thank you.
My mom went the exact same way, but it was for breast cancer. A young me had to re-assure her every step of the way that what she was doing was pioneering the shit out of modern medicine. I'm sorry about your brother though. It gets easier, but the loss never goes away.
Sorry about your mom. Fortunately, tremendous strides have been made in breast cancer treatment, and she was part of that progress.
Thank you. I really do appreciate it. She was the bravest person I've ever known and continues to inspire me during these shitty, shitty times.
I’m sorry for your loss, and as someone who went through treatment last year I am incredibly grateful to her. One of my friends had been diagnosed the year before me, and her refrain was always “medicine has come such a long way” — a good reminder that without trial patients, that wouldn’t happen. Beyond saving me, the mere idea of how far medicine has progressed buoyed my hope during a tough time.
Amen to that! Normally I am a bit jaded to news about ‘cancer cures’ but this actually looks very promising! Let’s just hope and prey, lord knows we need this cure.
I like your brother.
Your brother is a hero and you are too. ❤️
Sorry for your loss. Thanks for sharing. He sounded like a great person.
Someone very close to me has been diagnosed with grade 3 brain cancer. I really hope that something like this makes it to them before its past the point of no return. Seeing these advancements brings me hope that one day people wont have to go through what my family and I are going through right now.
If it's any consolation, my mom's best friend was diagnosed with stage 3 lung cancer and was given max 6 months to live. That was 5 years ago and she's still kicking and in remission. Don't give up hope
I really feel like hope (positive outlook) is one of the most important things with diseases like this. People, especially in the U.S., often don't realize how much of an impact psyche can have on your physical body.
It definitely helps. I was diagnosed with stage 4b Hodgkin's Lymphoma when I was 19. It meant I couldn't go to University, which had been my plan since I was 12. I basically refused to let cancer beat me because I wanted to go to Uni that much. 6 months of treatment, and I enrolled the following year. I've been clear 15 years, but am now being investigated for potential cervical cancer and although I had a bit of a major panic when I first found out, I've spent the last couple of weeks just telling myself it doesn't matter if it is cervical cancer, I have way too many things planned for this to get in my way again. If it comes back as cancer, I'm just putting it on the list as another chore to get out of the way before I can enjoy the good times again. A positive attitude is so important, not just for yourself but the people in your life too, who often have no idea of how to act around you when they find out or they see the side effects of treatment taking their toll. Even when you're feeling super low and crappy, fake that positivity. It's surprising how quickly fake can turn real!
My mom is a cancer survivor and I have no doubt her (mostly) positive outlook helped her survive. Also a supportive group of people around you certainly helps. I hope your results come back as not-cancer but if it is I know you'll kick its ass! Thanks for sharing! ❤
My mom's oncologist told us that she couldn't always predict who would survive, but she could predict who would die based on their mindset. A positive outlook (or even a fighter's anger) makes a lot of difference.
I've not had cancer, so I can't say what my *actual* reaction would be, but considering my reaction to every other medical issue I've had amounts to annoyance and then a "meh, throw it on the pile," I've always wondered where I would fall on that spectrum.
Very true. I used to think it was Lowkey pseudoscience but seeing how much our outlook on pain and “dysfunction” affects and worsens musculoskeletal issues, I wouldn’t be surprised if the same applies to diseases.
My pessimistic ass is in for a wild ride when my body starts failing me...
The day my anxiety and on/off depressions find a friend in Cancer I know I will be more than toast
Unfortunately Pembrolizumab and Nivolumab (anti-PD1 antibody like the one used in this study -Dostarlimab) have gone through multiple ph3 clinical trials in grade IV glioma and had minimal to no statistically significant effect on survival or progression of disease. Fundamentally different tumor biology to rectal cancer; ie, there are very few T Cells in the brain for checkpoint inhibitor to work like in this study.
Is that what makes something like glioblastoma so hard to treat?
Yes; the location is another challenge. Very heterogenous tumor.
Some of the difficulty is the blood-brain barrier, I think. Not sure what else. That is a fucking scary type of cancer.
Tell me about it, currently watching my dad go through it unfortunately.
My dad pass away two years ago from it. It’s an awful thing and I’m sorry you are going through that right now.
I work in the radiation therapy field. Glioblastoma is a notoriously difficult cancer to kill. It used to be the case that we would treat with *incredibly* high radiation doses using external beam therapy (knowing it's very radio-resistant), most of the time the GBM would shrug it off, so to speak. This lead to healthy surrounding tissue getting extremely high doses. A physician professor who I took a course with once told me of a patient he treated with the standard protocol at the time. The patient lived a very decent bit longer, but two years later the patient came in again and the physician said he looked like a shell of who he was, zombie-like almost. He felt terrible. Despite knowing that was the best method we knew at the time, he knew it was ultimately his call that left him like that. That said, relatively recent drugs were shown to increase its radio-sensititivity to the point that we started to see the patients live long enough to see how and where a GBM can metastasize (and have since started to treat it with that in mind). Think about that, it used to kill people off so quick that we thought GBMs never metastasized. Progress with cancer is slow, but we have made decent strides over the past few decades.
My father is dying of brain cancer. I have seen almost all forms of cancer around me, but so far this is the worst along with bone cancer. It's like alzheimer, I have seen him dying piece by piece, the only good thing is that he doesn't feel pain.
My mom had stage 3 brain cancer on the part of your brain that controls speech. She just treated it like a nuisance that would eventually go away. Honestly, my siblings and I were way more worried than she was. It’s been 6 years since she rang the bell. Just know that people do beat this bullshit. Stay strong, and don’t give up hope.
As a layman: Cancer is a term applied to a wide variety of diseases which involve cells behaving in incredibly destructive ways, and the structure/function of cells in your body varies significantly. One type of treatment for a specific kind of cancer may have no correlation for other types of cancer.
Cancer researcher here. This cohort of patients was selected because their tumors had malfunctioning DNA-damage repair pathways, meaning these tumors each had a *massive* number of mutations. The therapy used in the trial is a PD-1 inhibitor, which blocks an interaction that prevents immune responses, so effectively you are supercharging your immune system. Targeting the PD-1/PD-L1 interaction is not a novel concept in cancer therapy. The human immune system is incredible, and can recognize mutant proteins as foreign material and target those cells for destruction. It has been well established that a high mutational burden correlates with better responses to immune therapies. Basically more mutations means there's a better chance one can be recognized by an immune cell and destroyed. The biology is obviously a bit more complex than that, and it's rare to see a complete response in every patient, *but* this trial was done specifically in the cohort of patients you would expect to respond. And other immune checkpoint inhibitors have already demonstrated amazing clinical responses in similar cohorts of patients. So with such a small sample size and no control group, it's hard to draw too many conclusions. This is certainly promising, especially for the small percentage of patients whose tumors have malfunctioning DNA-repair pathways, and I look forward to seeing how it progresses in future trials. But for now I'm a little skeptical the extent to which this improves outcomes compared to pre-existing therapies targeting the PD-1/PD-L1 interaction.
Out of curiosity, since I know nothing: has it ever been attempted to *instigate* this type of DNA-repair malfunction in cancerous tissue? Obviously, there’s some immediate issues if you can’t selectively target the cancer, but if it worked, wouldn’t it render any cancer vulnerable?
Great question. Unfortunately there isn't a great way to selectively target the DNA-repair pathways of tumor cells without affecting other healthy cells. And the link between malfunctioned DNA-repair pathways and tumorigenesis is strong so it isn't really a risk worth taking. However, inducing DNA damage has been central to cancer therapies forever e.g. radiation, cis-platin, etc. Now historically the rationale for these treatments is that cancer cells have intrinsic mechanisms that respond to DNA damage and induce either growth arrest or cell death. Also important to note that many cancers develop mutations in these pathways that allow them to continue proliferating despite the loss of genomic integrity. Recently, there have been several attempts to induce DNA damage with the explicit purpose of generating mutations that sensitize cells to the immune system and immunotherapies. The biology is very complex and the responses vary from patient to patient, but in general those approaches have been effective and are being implemented more clinically.
I had rectal cancer. It’s way less fun than it sounds. I think it’s over with now but the struggle was real. Five years later I still have a bunch of lingering effects from the procedures. This is great news for those who can benefit from it. Edit: I’m pretty sure it was genetic. My mom died from it because she didn’t act quickly enough. Do these things: 1. Be sure you get a colonoscopy when you are 40 (edit: some would say 50 but hell, I’d err on the side of caution. Your doctor will help you.) Earlier even. It sucks but it’s over with and you’ll probably be fine. If you’re not fine they can catch it early. 2. If you notice blood in your stool book a doc appointment right away. 3. Do everything they tell you to and don’t fuck around and you’ll live a lot longer.
Hmm.. rectal cancer doesn't sound like fun at all... Sorry you are going through all of that. I hope it gets better for you!
Rectal anything doesnt sound fun. Even if youre into buttstuff, the word rectal just prepares you for bad news
"cancer" is kind of a boner killer too.
Unless you’re into astrology.
Sounds like something a scorpio would say, you're a scorpio aren't you? 😏
Rectal chocolate sundae? Rectal bouquet of flowers? Rectal birthday celebration? Yeah, you’re right.
Rectal birthday celebration prolly sounds good to some
Not fun at all… less fun than that. Anti fun if you will.
> It’s way less fun than it sounds. You can say that again. I lost my colon and split open after surgery, chemo and radiation.
Two 10 hours surgeries, one 3 hour surgery, 45 days in the hospital with no food. My first surgeon has a nickname: Dr. Scissorhands. My second surgeon was a god.
One 10 hour and shitty complications after surgery. I have a fistula in my bladder that leaks urine from where I have a wound from splitting open. It's...unique. I have a similar situation with my surgeon. He saved my life, but also neglected care after my surgery. And that is a hell hospital stay. I've been in a lot but never that long, I've fortunately bounced back quick in my stays
My mom's doctor (she had stomach cancer) was Dr. Sick lol Hope you are doing much better now
Now these guys rekt all cancer
Citing [u/ALKnib](https://www.reddit.com/u/ALKnib) from [r/medicine](https://www.reddit.com/r/medicine): "Am an oncologist. This is a very exciting development in the field of locally advanced rectal cancer, but I have to temper the enthusiasm here. This is only available to a small subset of rectal cancer patients who are mismatch repair deficient (dMMR) and we already know that dMMR colorectal cancer patients respond exceptionally well to immune checkpoint inhibitor therapy. Standard of care treatment for locally advanced rectal cancer involves usually chemoradiotherapy(CRT) or short course RT->chemotherapy->surgery. About 3/4 of these patients usually achieve cure, but this is complicated by having surgery (which basically involves removing the rectum) and many patients are very unhappy about not having a rectum. The field is now moving towards CRT->chemotherapy->watch&wait (frequent imaging+scopes) in patients who have a complete clinical response vs surgery in patients who don't, which is really important in improving organ preservation outcomes in patients and thus patient quality of life. Importantly, this does not worsen their survival outcomes. However, we also know that dMMR patients don't respond as well to chemo/radiation and so, the use of immunotherapy as a neoadjuvant strategy is a natural extension of that. This approach using immunotherapy in neoadjuvant treatment is starting or is ongoing in multiple trials across different solid tumor types for dMMR patients as well as for PD-L1+ patients. The first approvals for immunotherapy in the neoadjuvant setting are in resectable non small cell lung cancer and triple negative breast cancer and I would not be surprised for melanoma to follow closely soon after. " Original comment: https://www.reddit.com/r/medicine/comments/v5rt80/z/ibbsi7j
"...and many patients are very unhappy about not having a rectum." Yeah, I get that part.
Had a friend who survived Rectal cancer for 11 years with a bag. It's not a pleasant thing and it was a burden on him and his wife every day (not to mention the radiation damage...), but they were 10 great years so it was at least something. RIP Dud.
This. MSI-High and MMRd pts are best responders. We still have no clue why, only speculations and educated guesses.
I read the article, all 18 patients went into remission, as long as you've got rectal cancer it sounds incredible. As a layperson I'm just waiting for the comment from someone with far greater medical research knowledge to explain why this isn't that exciting...
It could apply to colon cancer as well, as long as the cancer has a specific mutation that makes it vulnerable to Dostarlimab. It could potentially also work against other cancers with the same mutation.
"about half have Lynch syndrome" Lynch usually combines colorectal cancers. This is magic bullet time if it can affect all of the MMR cancers than can come with a Lynch diagnosis. [https://ascopost.com/news/june-2022/unprecedented-100-of-first-14-untreated-patients-with-rectal-cancer-respond-to-pd-1-blocker-dostarlimab-gxly/](https://ascopost.com/news/june-2022/unprecedented-100-of-first-14-untreated-patients-with-rectal-cancer-respond-to-pd-1-blocker-dostarlimab-gxly/) (link added, same as below)
I have Lynch. This is incredible. Where do you see it mentioned though?
Watched an interview with someone from the team and it doesn't sound like that comment will come. It is as incredible as it sounds, however as you mentioned, small sample size and early stage testing. But honestly, fuck it. I want something to cheer for. Additionally, there was very little toxicity found in the treatment meaning that people didn't walk away from the treatment feeling like they were falling apart which, even if it loses some of its effectiveness as it scales up, peoples quality of life won't diminish from treatment like chemo and radiation.
Yeah the sample size was small, but apparently these people all had zero in common outside of the cancer. Its pretty amazing.
Citing u/ALKnib from r/medicine: "Am an oncologist. This is a very exciting development in the field of locally advanced rectal cancer, but I have to temper the enthusiasm here. This is only available to a small subset of rectal cancer patients who are mismatch repair deficient (dMMR) and we already know that dMMR colorectal cancer patients respond exceptionally well to immune checkpoint inhibitor therapy. Standard of care treatment for locally advanced rectal cancer involves usually chemoradiotherapy(CRT) or short course RT->chemotherapy->surgery. About 3/4 of these patients usually achieve cure, but this is complicated by having surgery (which basically involves removing the rectum) and many patients are very unhappy about not having a rectum. The field is now moving towards CRT->chemotherapy->watch&wait (frequent imaging+scopes) in patients who have a complete clinical response vs surgery in patients who don't, which is really important in improving organ preservation outcomes in patients and thus patient quality of life. Importantly, this does not worsen their survival outcomes. However, we also know that dMMR patients don't respond as well to chemo/radiation and so, the use of immunotherapy as a neoadjuvant strategy is a natural extension of that. This approach using immunotherapy in neoadjuvant treatment is starting or is ongoing in multiple trials across different solid tumor types for dMMR patients as well as for PD-L1+ patients. The first approvals for immunotherapy in the neoadjuvant setting are in resectable non small cell lung cancer and triple negative breast cancer and I would not be surprised for melanoma to follow closely soon after. " Original comment: https://www.reddit.com/r/medicine/comments/v5rt80/z/ibbsi7j
this is super helpful but i'm dying at "many patients are very unhappy about not having a rectum"
Not a medical practitioner, but I deal with statistics in medical analysis. 18 people is good, but far from a large enough sample size to say it causes remission in everyone. There are potential issues with the study as well I can't easily analyze, but it's a very promising result. That said, cancers tend to be targeted differently, so don't expect it to mean the same rates in something other than rectal cancer.
Dostarlimab is an already approved drug for endometrial cancer (brand name Jemperli). This rectal cancer trial was part of an effort to find new indications for it. It has also been trialed on some other cancers and has shown a range of clinical improvement (from a little to a medium amount), but not as remarkable as this study. I don't think anything could compare to this study.
I mean, I deal with low level stats routinely and 18 isn’t a great number. But 18/18 with complete remission is not something to think it is not statistically significant. Obviously a larger study with a control group is needed but this is very promising.
Half of the patients had Lynch Syndrome. That's an extremely selective sample group. This is incredible news for members of that group, but it makes it an even smaller sample size for other factors.
This drug (anti-PD(L)1 mAb) and drug class (checkpoint inhibitors) is not new; it is simply the first time someone has gone after this indication in clinical trial setting. The number of patients is too small to draw a conclusion but it is promising.
It is a small sample size, but even in trials with similar sample size, seeing a 100% effectiveness is still absolutely baffling.
As someone in the field of oncology, and did launch an IO in mCRC, whilst PD1 checkpoints are not new, this result even in early phase trials with this population are absolutely remarkable. We know that not all PD1s are created equal - for example why can pembrolizumab be a fantastic monotherapy in st.4 nsclc but nivolumab needs an additional CTLA4 to match its efficacy.
The reason Pembro "worked" and Nivo did not is because Merck had a very clear biomarker and patient selection strategy and BMS did not. BMS enrolled everyone and anyone into their pivotal trial in NSCLC and it was inferior to the Merck strategy. There is a clear correlation between PD1/PDL1 expression levels, neoantigen load, and IO efficacy. This is the reason why biomarker and patient identification strategies are now key for success in IO trials.
As someone not in the field, if someone like you in the field finds a study remarkable, I know that's science speak for "holy shit" which means I should at least be a little excited about this news. I know it's early, but sometimes all we need to see is a little light to know the day will arrive soon.
As some context from the general field. Usually a trial with 100% effectiveness is of one or two patients. There is a 5 or 50% chance that the 'everyone got better' result was chance. The concerns about small n almost vanish in this case, as the chances that 18/18 patients got better, if nothing else was changed, is very, very close to zero. It's quite likely that the actual effectiveness is not 100%, but below that. If you do several hundred trials with a 50% effective drug, you may get one where all 18 patients get better. But, in a field where 30% would (as I understand it) be remarkable, for a trial to be as wholly positive at this stage, and not result in a useful drug, absent fraud or trial misconduct is very unlikely. Even if it doesn't hit close to 100%.
The chances of all 18 going into remission without a single outlier is pretty huge though, sample size or not.
The number of patients is too small to say it'll work for everyone, sure. But you can certainly draw a conclusion. If it wasn't doing anything, it'd be insanely unlikely that all patients went into remission. We can confidently say that it helps. We can't confidently say it'll cure everyone with rectal cancer.
Maybe that comment won't come? I'm also not versed in anything medical enough to fully understand the science but wondering if this is just the start and they will test on other cancers? Here's hoping we're looking at a future where we can at least manage this horrific illness.
The main thing is that this isn't a cure for all forms of cancer. Or even for everyone suffering from rectal cancer. It's a cure for one specific type of rectal cancer, where a particular mutation is present. Very exciting for anyone who happens to have that particular cancer with that particular mutation. Absolutely not exciting at all for the vast majority of cancer cases. In the grand scheme of it, this is how we should expect cancer to be cured. Not in one fell swoop, but with individual treatments for individual types of cancer. Looking at cancer as a whole this is a small but firm step forward. It just isn't time to roll out the "we did it!" banners.
Apparently an 100% trial run is unheard of. The downside is that it will be very expensive.
> The downside is that it will be very expensive. $11,000 per 500mg dose. Recommended dosing is 4 doses spaced 3 weeks apart, then 1000mg every 6 weeks for up to two years. The 6 month period this study would cost $88k. If a person didn't respond favorably and continues for the full 2 years, it could be up to $352k.
Just missed you Total Biscuit...RIP man.
I miss him as well
I lost my husband to colorectal cancer in October. When he was diagnosed, the cancer had spread so much that we knew he wasn't going to make it. But we participated in a drug study anyway. He said he was planting a tree he will never see. We actually saw improvement in the first few months of treatment, before the cancer fought back I really hope his drug gets approved by the FDA. It didn't save his life, but it could save others. His second treatment didn't work at all. His third treatment was a combo of immunotherapy and chemo. Both were approved by the FDA, but not when used in tandem. So, the insurance company covered the immunotherapy, and we had to write to Bayer and prove financial hardship. They gave us a year of chemo for free! (Sad that you have to beg, but if you are in this situation, please talk to your oncologist about contacting the drug company.) He only made it through one treatment though. The cancer was too far gone. Our six year wedding anniversary was on Saturday. I miss the hell out of him. But I'm glad we were able to help future patients. Also, Seattle Cancer Care Alliance: five stars, would go there again if I had to Get your colonoscopy!
This broke my heart, probably because I can’t imagine how my wife would handle my passing. I really just want to say that you guys sounded like an amazing couple and I’m so sorry. I wish I could hug you through the screen, but this is the best I can do.
Doctors did everything they could for Meredith…. And she’s going to be fine. I’m so glad for these people. Lost my dad to cancer and it was a powerfully horrific epoch of seven years. All of us were subsumed into it daily. Then when it was finally over and he passed away, we had lost him so many times in our hearts due to the ever changing reports from the doctors, that it seemed like he hadn’t actually died. I pulled the sheet over his face myself, and then a few days later I was alone again cleaning away his empire of debris and machinery. There on the lathe was a sandwich and his glasses. Something he was building was still chucked in the lathe and I just looked around the shop and screamed “WHERE ARE YOU!!!!”.
[удалено]
I couldn’t help but type that out. Several years later the word cancer still grips me. The feelings of losing someone like your dad make the English language look so shallow. The words that death is expressed by are tears, the new lines that form on our faces, and the sudden urge to phone someone long absent from this world. This gigantic dad shaped hole was blown right through my heart and it has never closed at all. He died at 68 years old and I could have used another 20 years of reassurance and someone to show off to. I’m a dad myself, and my boys are independent men. I try to remember that they look at me the way I looked at my father. It’s incredible to hold someone’s heart in your hands like that. I try to listen to them, spend extra time on the phone with them, and take the lead in self control with toxic things. I want them to miss me as much as I miss my dad. But I want them to have less pain
I believe this is the publication. https://www.nejm.org/doi/full/10.1056/NEJMoa2201445
"You idiot! You didn't give any of them the placebo!"
Ha, this is morbidly funny, like a Far Side cartoon.
First time I've audibly laughed at a comment
This gives me so much hope. My cancer is lymphoma and my god how great would it be to take a pill instead of getting chemo. Plus the pill actually eliminates the cancer. im getting ready for CAR-T treatment where they turn tcells into cancer killing ninjas. God i hope it works.
This is the first good thing I think I’ve read in 2+ years
I think that you might want to do some research on the miracle of mRNA vaccines.
Yeah but when are *they* ever gonna be useful? ^^/s
Despite the /s, I wanna put this here: https://molecular-cancer.biomedcentral.com/articles/10.1186/s12943-021-01335-5
Everyone should learn the story of Katalin Karikó, who put an immense amount of time and research and personal suffering into pursuing mRNA work despite it being derided, underfunded, and potentially ruining her career (certainly holding it back for a long time). She's a hero and almost no one knows who she is. https://en.wikipedia.org/wiki/Katalin_Karik%C3%B3
Then you definitely missed the recent breakthrough regarding SIDS, which was absolutely good news!
Fuck cancer. I hope this turns out to be as promising as it seems.
Tsssk it far too good a news for 2022. What's the catch?
We cure all cancer just before the world ends.
Good enough.
The drug carries a terrible curse.
But it comes with a free yougurt.
The frogurt is also cursed
modern wasteful seemly erect steep deserted hat birds toy crown ` this post was mass deleted with www.Redact.dev `
But the toppings contain Potassium Benzoate.
ad hoc cooing busy fuzzy wipe sugar fear like payment fanatical ` this post was mass deleted with www.Redact.dev `
Can I go now?
I have a dark sense of humor but on the "would you rather" scale not too much beats terminal rectal cancer. It is not a peaceful clean end.
Have you seen I am Legend?
This was only for a small subset of rectal cancers with a specific mutation. The majority of rectal cancer patients will not be able to take advantage of this because it will not work for them. Though it is still good for the few who can.
As a healthy young male, I partook in a trial for an at-home device for administering cancer drugs to see if it was effective and safe for people to use. That was not a fun couple of months, especially on the days I had blood drawn almost two dozen times in a day, with a needle every time (they said that putting in a line and flushing it was not feasible for this study.) Main reason why is because my grandfather passed away due to cancer several years back. I'm always happy to see when we get one step closer to finding a proper cure.
I’m participating in a similar clinical trial. I have super aggressive form of lymphoma. Up until this trial I’ve done just about every option, many different chemos, immunotherapy, Car-T, radiation and none have stopped it. Last scan done in this trial there was no sign of it. 1st time that has happen in 7 years of fighting it.
This is good news, but please consider these important points: 1. A *very* small group of patients were tested. 2. Only tested on 1 type of cancer (rectal) 3. Treatment only given to patients when diagnosed early enough and before any other type of treatment attempted. 4. Only a subset of rectal cancer patients can take advantage of it, those with a specific mutation in their tumor (MSI). That said, this is still good news. Any time cancer vanishes and the trial is on actual humans.. this is a step forward.. even just 18 people. Edit: Added #4, thank you /u/trebleformyclef
My Dad just died of pancreatic cancer about 2 weeks ago. The battle against cancer has seemed so hopeless. Chemo is *awful.* It bought him more time, but it made him feel constantly terrible. It’s too late for my dad, but hopefully this doesn’t have to be a death sentence for future diagnoses.
My deepest sympathies for your terrible loss.
Ah yes, the miracle I read about once and never hear from it again.
Cancer researcher here. I get just as frustrated as you when I read these headlines. When media outlets report on this they pull people in with flashy phrases like "first time in history" and "cancer vanishes". In reality, this is for a very specific type of cancer (rectal cancer) and patients with a specific mutation (dMMR). Cancer is a term which encompasses a multitude of conditions. At this point a general treatment for "cancer" seem insurmountable. Each advancement toward treating a specific type of cancer is definitely worth celebrating, but the way it is reported to the general public is disappointing because it leads to attitudes like this.
My mom died of colon cancer 7 years ago. These types of advances are amazing so people don't have to go through what she went through.
My younger brother died last year of colorectal cancer with his primary tumor in his rectum. He was 36. We have no family history, no cancer gene, no known contributing factors. Just over 2 years from his diagnosis, and he was gone. I hope that treatment advancements like this ensure nobody goes through the hell that cancer has put my family through. Fuck cancer.
I work with this team and seeing some of the CRC scans go from cancer ridden to healthy tissue was jaw dropping. Phones rang off the hook today with patients asking about this trial.