Hello Edward and Renee,
I hope you are both well. I enjoyed reading your book so much - well done. I think you are both AMAZING. Reading it was in anticipation of this day, which i have been dreading, when I would learn that my sarcoma has finally metastasized to my lungs. I'm 57, in excellent health, except for sarcoma! First diagnosed 5 years ago. original tumor is under control per most recent to MRIs - original surgery in 2012, then recurrence near original site 5/16 .completely resected again followed by proton therapy in Sep 2016. Next scan turned up 2 lung mets - I had VATS surgery 3 months ago to remove them , but recent CT revealed 5 more small ones (although 1 is 1.4CM). The oncologist has recommended starting doxirubicin with olaratumab very soon. I'm told it has 1% chance of cure, but slowing down progression possible. very discouraging. To date I have had only surgery and radiation, no chemo. before agreeing to this I want to explore more about immunotherapy.
I talked to the thoracic surgeon that did my VATS surgery in April, , asking if cryoblation was an option - although he says they do that here (Boston) he wasn't too keen on its idea but encouraged me to continue to research.
Would it be feasible do you think to combine cryblation with PDL-1 Blockade? I understand these would both likely be out of pocket expenses. Whom would you contact about cryolbation? Dr. Littrup? is he still doing this?
Do I have this right that the cryoblation could freeze the tumors, and could leave behind a vaccine like "abscopal" effect on the sarcoma? I was told that in a few studies they have seen a 13-15% response rate for PDL-1 blockade on sarcoma (not great, but better than 1%). I was told they would only use that if there were an unresectable lesion they could follow by CT scans. so maybe if they could cryoblate as many tumors as possible, then use the PDL-1Blockade afterwards? does any of this make sense?
Is Dr. Littrup still the person you would reach out to see if cryoblation is an option?
Many thanks for your book and sharing your journey and knowledge.
Mary Beth
Hi Mary Beth,
We're sorry to hear of the challenging recurrences. As you well know, it is a characteristic trait of sarcoma.
If you've read our book in its entirety, you'll see we absolutely endorse cryoablation.
Here are some of our thoughts about your situation:
1) Yes, cryoablation has been documented to trigger the abscopal effect for many decades already.
2) Decades of research corroborates the very low chance of curative chemo (i.e. 1% that you were quoted). 13-15% is 13-15x better than 1%. So a no brainer in our view. You can get PD-1 off-label and/or clinical trials.
3) *Independent* of PD1 or chemo, long-term survival has been documented in about 30% of sarcoma patients who only have lung mets -- simply by repeated "weeding" of lung tumors with surgery. Do you have tumors elsewhere? Are the existing lung tumors inoperable? In our view, it is a top priority to attack these tumors with physical methods (surgery is OK, but far better is cryoablation). We tried to communicate clearly in our book just how amazing cryo for lung tumors -- especially small ones. The thought of a needle poking into one's lung might be scary but it really is a cakewalk in comparison with lung surgery (even VATs).
As we tried to convey in our book, every surgeon we've ever consulted dismissed cryo. But they weren't qualified to speak meaningfully about it. Some claimed they had "experience". But cryo technology has advanced considerably and you need to speak with someone like Dr. Littrup or Dr. Aoun to get a meaningful understanding of pros and cons. (Here's their contact info: Dr. Littrup (http://www.cureasps.org/forum/viewtopic.php?f=55&t=1296) or Dr. Aoun (http://www.cureasps.org/forum/viewtopic.php?f=55&t=835)
If money is an issue, you could conceivably cryo all "dangerously located" tumors and leave one untreated to qualify for a PD-1 clinical trial. That would save you PD-1 expenses.
As described in our book, we'd cryo first before PD-1 and try not to have too much a time gap in between. And we would not do high-dose chemo before immunotherapy as described in our book -- it can weaken the immune system. (Some low dose regimens could synergize with immunotherapy, but you need to work with someone with experience who understands what s/he is doing).
So, to summarize, the #1 "proven" strategy for sarcoma pts with only lung mets is surgery (much better is cryo, if you can afford it, because of the low morbidity and potential immune synergies). And in terms of systemic treatment, PD-1 might offer 13-15x better odds than the 1% chemo offers. Don't lose sight of the decades of hard data that "proves" chemo won't cure you.
Keep thinking independently and examine the options objectively.
All the best,
Edward & Rene
Thank you so much for your thoughtful and detailed reply. As far as I know, the metastasis is only in my lungs, but who knows what cannot be seen. I have contacted Dr Littrups office and am waiting for a call back. In the meantime I was able to talk to an interventional radiologist that does cryblation in the same hospital I have been treated for my sarcoma for 5 years. He could cryoblate a few he said, but 1 or more of the largest tumors are centrally located and couldn't be reached by the needle. Advised to follow my oncologists recommendations do the traditional chemo. He is reading your book now! As he was curious how I came across this approach. He is working on a lung cancer trial that does the cryo with the PD1 soon, but sadly won't be available to sarcoma patients. My sarcoma oncologist, whom I do trust and like and have known for 5 years now says that the cryo/pd1 option is interesting and experimental and we could try if the usual and considered more successful approaches (chemo) do not work. But I'd rather try it first, as you say, before the chemo wears down my immune defenses. How would you advise getting the PD1 piece coordinated? I'm told it takes a team to agree on something outside the box, and I don't have a team onboard with this. Do you know of any medical oncologists that subscriber to this I could contact?
I think this has become aggressive, as so may tumors popped up just since last scan inMarch and surgery in April.
On another note- if there is microscopic disease elsewhere than my lungs, would the PD1 work on that too hopefully? Assuming it's all the same sarcoma.
Or is that aspect a vote for chemotherapy?
Many thanks
Mary Beth
Hi Mary Beth,
Regarding the central lung tumor, our experience consulting various physicians informs us that second, even third opinions are often necessary. A practiced cryoablationist at MSKCC once told us there was no way he would dare cryoablate Rene's recurrent jaw tumor for fear of puncturing an artery. In stark contrast, Dr. Littrup who by then had by some estimates treated 1000 tumors, had absolutely no reservation about cryoablating it. He was able to safely and accurately surround her tumor with 4 probes, stuck straight down the cheek, reaching far back into the jaw.
The point: Like surgery, technique and experience matters for cryoablation in our opinion.
For easily located/ablated tumors, it may not matter much who/where you do it, esp. if travel/cost is a limiting factor. This is even more true in the setting of likely metastatic disease where the importance of "curative" ablation becomes less (unfortunately). Remember that cryo can always be repeated -- so if an easily treatable tumor is ablated but regrows, you can always re-ablate it. That said, the issue there is successful monitoring as the post-ablation inflammation may sometimes obscure tumor regrowth.
Regarding "it takes a team", unfortunately, such teams exist almost exclusively for "proven" modalities - surgery/chemo/radiation. As you can see from our experience, we had to do it piecemeal, flying to where the individual expertise was. Our advice/encouragement to you here is that even though it may take hard work/money, ultimately, the cancer and your immune cells don't really care where or how you get the individual components -- just that you do! One thing you could do is scour for cryo + PD1 combination clinical trials. I don't see any now on clinicaltrials.gov for sarcoma. But NCT02469701 is for NSCLC. Sometimes, a non-sarcoma trial might be willing to admit sarcoma patients. Furthermore each site for the same trial could give you a different answer. I would definitely call the sites for NCT02469701.
There is also off-label PD-1 where if you can find a clinic that's not bent on making their 400% profit, you might get infusions at $5000? per infusion (not sure what the going rate is today).
Regarding different types of cancer in different body areas, there simply is no way to know for sure, but the likelihood is probably very low. (But yes, there are patients who get multiple cancers.) I don't think the presence of different cancers would argue for chemo above PD-1. Of course, this depends on whether said chemo has demonstrable activity for the individual cancers. Personally, in this hypothetical/unlikely scenario, I'd think PD-1 is arguably the better strategy -- as we pointed out in our book, this single approach was (and continues) to be approved for multiple different cancers.
Finally, regarding what the sarcoma oncologist you trust and have known for 5 years said -- i.e. that the "more successful" chemo approach should be tried first. In our view, there are 2 separate issues to focus on:
1) S/he could be right in that chemo could shrink that central tumor and enable surgery/cryo. (in other words, the 1% chemo cure rate should not be confused with a potentially higher ability of chemo to *shrink* tumors.)
2) A 1% cure rate attests to the near certainty that chemo cannot eliminate unseen microscopic disease.
We know there aren't clear cut answers. Rene always encouraged (and continues to encourage me) that whatever difficult decision we make, we should do it with no regrets, knowing that we tried to make the best decision with imperfect information. Whatever path you choose or create for yourself, we wish you the very best outcome.
Hi Ed and Renee,
How do I find a clinic that will prescribe the PD-1 to me off label? (preferably at less than the 400% mark-up as you suggest - yikes!)
Also, do you think the fact that I had adenocarcinoma (discovered incidentally while monitoring my lungs for the sarcoma and removed 18 mos ago successfully via VATS surgery) be apt to make the cryo-PD-1 combo less effective? I learned today that it would make me ineligible for many clinical trials unfortunately because if something started to grow while on the trial they wouldn't know if it was the sarcoma or the adenocarcinoma...MB
Hi Mary Beth,
From your previous posts, it sounds like the 5 lung tumors are sarcoma, not adenocarcinoma? (based on the chemo regimen your oncologist has prescribed).
As alluded to in our previous email, PD-1 could potentially work against multiple cancers, not just one. Naturally, any cryo would be releasing a shower of antigens of the cancer/tumor that you're cryo-ing only. Still, PD-1 monotherapy (without cryo) has shown efficacy against NSCLC. Why do you think the presence of 2 cancers make it less effective towards any one?
We understand your frustration about not qualifying for trials. Indeed, that is the nature of clinical trials -- if they can't track it, you won't qualify -- unless it's a trial where they administer an agent to prevent recurrence (in which case you would try to remove all tumors, then track for recurrence).
PD-1 off label:
A few years ago we saw a doctor who was willing to prescribe PD-1 off label at cost. The big hospitals like MDA, MSKCC, MGH etc will all likely tack on huge markup. Their charge masters will see to it and oncologists don't have power to veto. As we wrote in our book, it's likelier that smaller clinics or solo practitioners may be able to administer it at cost price.
You can call around to smaller practice groups or solo docs in your neighborhood, especially those treating NSCLC or Melanoma who have experience managing PD1 toxicity. We heard from another patient on this forum about a doctor in NJ who was able to offer PD1 for compassionate use. We have no personal experience with him though. He is Dr Neil Morganstein (Summit Hospital in NJ).
Personal neoantigen vaccine prompts strong anti-tumor response in patients, new study shows: - recent Dana Farber article. I have frozen tumor from.my sarcoma recurrence in May 2016. At the hospital I believe. Can a vaccine be made from frozen tumor? Or does it need to be live tumor? Then building on layered attack, , cryoblate a few of my lung tumors or as many as possible (one cryo doc suggested microwave?) to generate the T cells/antigen and follow it up wit the Pd1, cross fingers Pd1 won't give me an autoimmune disease. Would they consider making a vaccine for me personally? Or too Star Wars?
Next week will be very pivotal, will learn whether my five lung mets and I are candidates for Cryo. Also 2nd opinion at Sloan Kettering. followed up by Dana Farber. Just hope I'm not taking too long to gather my info as my mets continue to grow...am drinking fish oil and trying to stay away from the omega 6 , and no cocktails...bummer...but figured that might be a good idea. . Thanks for listening to me ramble. Ordered a couple more books to bring to my saecoma poointments in case they had not seen. Mary Beth
Hi Mary Beth,
Vaccines can be made from frozen tumor. It all depends on the type of vaccine and who's making it. Whole-tumor vaccines have been around for a very long time. Neo-antigen vaccines are thought to be "more powerful".
Personally, we do not think it is worth the trouble or time delay to pursue a personalized vaccine unless you can get it right now -- and only if done by a reputable group who knows what they're doing. We would just go for cryoablation in combination with other systemic immunotherapy (PD-1, IDO etc, even Omega3/6). We think cryo can be good enough to create an in-situ vaccine. If not all 5 mets can be cryoed, you could always cryo one or two tumors. A (possibly inferior) alternative might be radiation to one or two tumors.
FYI, this recent finding
http://www.oncologynurseadvisor.com/general-oncology/celecoxib-improves-...
is one of many theoretical underpinnings of why we believe Omega3/6 is synergistic with immunotherapy (Omega3 is a COX-2 inhibitor but unlike drugs that have a half-life and may not penetrate all cells, we believe it is potentially far more powerful in that it can incorporate into all cells and *stay* incorporated).
If you're doing omega 3/6, we recommend doing it systematically and seriously (ie be strict about calculating omega-6 input, document intake of omega-3 and work with your oncologist esp. to head off any potential blood thinning effects from surgical procedures)
Best
Ed & Rene
The problem now is finding an oncologist who will support me in all of this. (trying cryo, then prescribing PD1 therapy along with fish-oil/low omega 6/low carb diet). Mine does not feel there is enough evidence to support all of this. And that the autoimmune potential effects of the PD1 are too risky and they don't always know how to stop them. If I react badly to the chemo, he said they have more experience with dialing it back, or changing regimens. The cryo docs are not involved in the immunotherapy piece. I have 2nd & 3rd opinions set up at high volume sarcoma centers with respected oncologists, but fear I will hear the same thing - chemo per protocol. Meeting with a cryo doc this afternoon to learn more about whether I am even a candidate with my current 5 nodules. I have an appointment set up with a nutritionist who I hope can help me with the diet portion (combining ketogenic with low omega 3) which I am trying on my own right now. I just googled IDO per your mention in your last post...even more confused than before. saw some trials with PD1, but not looking so promising. this is all overwhelming. Thank you for listening to me...
Mary Beth
We understand the disjointed care when trying to piece together an immunotherapy strategy. Chapter 16, Section "Driving your own cure", pg 273-281, contains our tips on how we approached this.
It is true that most sarcoma oncologists are more familiar and comfortable with chemo/radiation/surgery as the treatment modalities. It may be more informative to consult with a sarcoma oncologist who at least is running an immunotherapy trial for sarcoma. He/she may have more understanding of immunotherapy.
I compiled some sarcoma immunotherapy trials at MD Anderson here, see "Sarcoma Immunotherapy Trials", post #6 at http://www.curingcancerbook.com/where-can-we-get-slides-tested-ny-eso1-e...
Hello Rene and Ed,
I hope you are well. I'm wondering how soon after your ablations did you re-commence with the fish oil and neuromins?
thank you,
MB
It was only after my last cryo that I did the high omega 3.
1 week after cryo, I started the ketogenic diet (for a total of 26 days). Then at 2 weeks after cryo, I layered on the high omega 3/low omega 6.
Hello Rene and Ed,
Don't know if I should change topic to Synovial Sarcoma? Last summer you were so helpful to me. I wanted to update you in hopes it may be helpful to you or anyone else. In July 2017, my first scan after VATs surgery to remove a lung MET revealed newly appearing and enlarging lung mets – just since the surgery a couple months prior. After much consideration and agonizing I decided to deal with the cancer we did know about first to buy some time. The oncologists were not on board with this. I had SBRT on one tumor that was not amenable to ablation, and 4 others microwave ablated. Most recent scan just showed all tumors treated appear dead and no evidence of new disease. I can highly recommend Dr. Damian Dupuy to anyone on the East Coast, or anywhere, who is considering tumor ablation (microwave, cryo, etc). see https://www.capecod.com/newscenter/a-hot-or-cold-option-for-cancer-care/ He is a pioneer in this field and has been wonderful. He gave us the first glimmer of hope when we met and said “I have good news for you, your tumors are treatable.” The microwave ablation procedure itself was very easy compared to VATS – I was home the same day. 3 tumors ablated in one lung one day, then about a month and a half later one in the other lung. I was incredibly lucky that no other tumors showed up in the meantime.
I continued my quest for immunotherapy. Genetic testing revealed the presence of an SS18-SSX2 fusion that was not previously known. FISH had been negative for the SS18 rearrangement – so Synovial sarcoma had been ruled out in 2012 when I was originally diagnosed. This genetic test was not available back then. With this new news in hand, and your book as my guide, I explored clinical trials. The Cancer Research Institute https://www.cancerresearch.org/ was very helpful in this regard. I ultimately was accepted into a phase 1B trial for CMB305 vaccine which targets NY-ESO-1. Turns out my tumor expressed that protein 100%. They are starting a phase 3 trial for CMB305 soon.
It has been quite a year. An emotional roller coaster to say the least. I cannot thank you enough for sharing your experience. Your book and answers on this forum gave me hope and the courage to take a step back and deep breath to explore different options that may not be considered “standard of care.” Most of all your book showed me that you do have a choice in your treatment plan. I learned you may have to be pushy (in the nicest way possible) to get answers, genetic testing for your tumor, and info about clinical trials. It feels like they are on the brink of some wonderful discoveries in the field of immunotherapy. Whether or not in time for me, the jury is still out. In the meantime I am feeling incredibly grateful, hopeful, and lucky. Thank you again for all of your hard work and sharing your knowledge. Sending you heartfelt thanks and healthy wishes. MB
Hello Rene and Ed,
Last summer you were so helpful to me. I wanted to update you in hopes it may be helpful to you or anyone else. In July 2017, my first scan after VATs surgery to remove a lung MET revealed newly appearing and enlarging lung mets – just since the surgery a couple months prior. After much consideration and agonizing I decided to deal with the cancer we did know about first to buy some time. The oncologists were not on board with this. I had SBRT on one tumor that was not amenable to ablation, and 4 others microwave ablated. Most recent scan just showed all tumors treated appear dead and no evidence of new disease. I can highly recommend Dr. Damian Dupuy to anyone on the East Coast, or anywhere, who is considering tumor ablation (microwave, cryo, etc). see https://www.capecod.com/newscenter/a-hot-or-cold-option-for-cancer-care/ He is a pioneer in this field and has been wonderful. He gave us the first glimmer of hope when we met and said “I have good news for you, your tumors are treatable.” The microwave ablation procedure itself was very easy compared to VATS – I was home the same day. 3 tumors ablated in one lung one day, then about a month and a half later one in the other lung. I was incredibly lucky that no other tumors showed up in the meantime.
I continued my quest for immunotherapy. Genetic testing revealed the presence of an SS18-SSX2 fusion that was not previously known. FISH had been negative for the SS18 rearrangement – so Synovial sarcoma had been ruled out in 2012 when I was originally diagnosed. This genetic test was not available back then. So the diagnosis was changed from epithelioid spindle cell sarcoma to an unusual biphasic synovial sarcoma. With this new news in hand, and your book as my guide, I explored clinical trials. The Cancer Research Institute https://www.cancerresearch.org/ was very helpful in this regard. I ultimately was accepted into a phase 1B trial for CMB305 vaccine which targets NY-ESO-1. Turns out my tumor expressed that protein 100%. I started receiving the vaccine in February. so far, so good. We shall see, but I am hopeful. They are starting a phase 3 trial for CMB305 soon.
It has been quite a year. An emotional roller coaster to say the least. I cannot thank you enough for sharing your experience. Your book and answers on this forum gave me hope and the courage to take a step back and deep breath to explore different options that may not be considered “standard of care.” Most of all your book showed me that you do have a choice in your treatment plan. I learned you may have to be pushy (in the nicest way possible) to get answers, genetic testing for your tumor, and info about clinical trials. It feels like they are on the brink of some wonderful discoveries in the field of immunotherapy. Thank you again for all of your hard work and sharing your knowledge. Sending you heartfelt thanks and healthy wishes. MB
Thank you for sharing your journey and resources with us and others on this forum!
We're so glad you are doing well after much persistence in treating the lung mets, getting a correct diagnosis and in pursuing immunotherapy treatments via clinical trials.
We wish you continued good health!
Mary Beth,
I am super excited to hear you’re doing well. Our stories have a lot in common and I would LOVE to connect with you. I was diagnosed with unclassified pleomorphic/unclassified spindle cell sarcoma about three years ago, mets to lung about 2.5 years ago. I am also in Boston! Originally at DF, most recently MGH, and moving to Sloan Kettering in NYC. Like you I wanted to pursue immunotherapy and like you none of my providers are on board.
So I’m actually just finishing a combo of optivo and yervoy plus fever therapy and hyperthermia in Vienna Austria and am hoping to coordinate care with a sarcoma specialist on the east coast.
That last part is up in the air so we will see what happens. Please email me at
(Email removed to protect privacy) or let me know how to contact you. You sound very knowledgeable and us sarcoma folks seeking immunotherapy need to stick together. I’m excited to research the trial you’re on!
Take care,
Mo