Hi Rene and Edward,
I have read your book in its entirety and it greatly assisted me in learning about potential treatment options, being your own advocate when dealing with the medical profession and much, much more. I felt it so beneficial that I ordered a second copy for my parents to read. So thank you!
My father was diagnosed with Metastatic Undifferentiated Pleomorphic Sarcoma in mid December 2017. 70 year old male in otherwise healthy physical condition, no pre-existing conditions, no history of previous disease, etc. The primary site is his knee and has progressed to his lungs (around 30 mets).
He received 10 days of radiation to the knee, ending January 3rd. The primary tumor had shrinkage in the initial week of radiation of around 1 cm. (Now approximately 14 cm across.) No treatment was done on the lungs as the number of mets and spread meant any type of resection, lobectomy or radiation, etc were not options. There was no abscopal effect from the radiation seen within the lungs, as confirmed by a recent repeatChest CT showing growth in size and increase in number of lung mets.
We finally had our appointment with the medical oncologist on Friday, who provided him with two potential treatment options:
1) Doxorubicin + Olaratumab
2) Clinical trial of Durvalumab and Tremelimumab (NCT02879162)
The doctor essentially said that any treatment option or clinical trial is a roll of the dice with this cancer. In terms of progression free survival, no treatment option has shown a significant improvement/results.
I had done much reading prior to the appointment and had not heard of Durvalumab and Tremelimumab in my travels. The doctor said that Durvalumab "was similar to Pembrolizumab in that it was a PD-1 inhibitor" and Tremelimumab "was similar to Ipilimumab as it was a CTL-4 inhibitor". This trial is a Phase II study of patients with advanced rare tumours, not specifically targeting sarcomas, and the combination of drugs had been tried on only 250 people.
1. Have you heard of these drugs before and is "similar" just as effective as the big names that I have heard about (vs. Pembro and the Ipilimumab, among others.)? I am wondering if we should be seeking other clinical trials, even if that means travel to the USA. (We are based in Edmonton, Alberta, Canada.) Perhaps there are trials of drugs that are more widely recognized that may prove beneficial?
2. What are your thoughts on treatment options? Have you heard of anything else that may be worth us looking into?
3. I have tried looking into cryoablation, but have not received a call back from Dr. Littrups office and have had little luck reaching someone in Canada that provides this treatment. (I tried seeking out Dr. David Liu, but had no luck in reaching anyone that knew of him or cryoablation.) Do you have contact numbers for either of these doctors and/or could you suggest another doctor in Canada that provides this treatment? Also, do you know if 30 mets is an untreatable amount? (I don't believe John German doctor that lasered away his 130 mets is an option in our case.)
4. Your omega 3/6 diet is something I should look further into. Are there any specific, reliable websites that you could send me to for recipes, supplements recommended, etc.?
Thank you so much for your time! Your contribution is truly appreciated.
Sincerely,
Jamie
Hi Jamie,
We're so sorry your father is battling metastatic sarcoma.
Thoughts on treatments -
1) cryo - Completely cryo’ing 30 lung mets along with a primary tumor still present will most likely not be possible. However, if the cryoablation doctor is attuned to immunotherapy, it may be possible to cryo only 1-2 tumors (for the purpose of generating T cells), followed by checkpoint blockade (from a trial or off-label). For information on obtaining cryoablation from Canada, do reach out to Olga on this forum, as she’s very resourceful with regards to cryoablation and based in Canada: http://www.cureasps.org/forum/viewforum.php?f=55&sid=f18a14c0d43d7e5953e...
2) laser lung surgery - 30 lung mets is possible, but they probably will want the primary tumor to be removed before the lung surgery (to ensure the primary tumor doesn’t keep on seeding new mets)
3) clinical trials -
Doxorubicin is chemo + Olaratumab is a targeted therapy. You’ll need to ask the oncologist what the effectiveness of this combo is. Bear in mind that many chemos and targeted therapies can shrink tumor, but does not get rid of all of it. So after a certain # of months of shrinkage on the treatment, treatment-resistant tumors grow back quickly and are uncontrollable by those treatments.
Durvalumab is anti-PDL1 ("PD-L1 blocking antibody", Chapter 7, section "How PD-1 inhibitors work", pg.118) and Tremelimumab is anti-CTLA4 (Chapter 7, section "How CTLA-4 inhibitors work", pg. 117). If I were in your father’s situation with only the options you listed, I would do this trial immediately after radiation or cryoablation (of 1-2 tumors) to try to get the abscopal effect. Do bear in mind that the double checkpoint (especially with anti-CTLA4) has worse side effects. It’s important to work with an oncologist who is experienced with checkpoint blockade so side effects can be immediately controlled.
Our thoughts on strategy are briefly summarized in Chapter 16, section "What I would do if my cancer returns", pg. 281. We touch on our thoughts about the double checkpoint treatment (anti-CTLA4 and anti-PD1).
4) omega 3/6 - We wrote up the guidelines we follow here:
Omega 3 supplementation: http://www.curingcancerbook.com/diet/high-omega-3-supplementation
Omega 6 diet: http://www.curingcancerbook.com/diet/low-omega-6-diet
We will write here again if we think of any other treatments that may be helpful for your father.
Take care and keep up hope!
Thank you, Renee and Edward, for your very detailed response.
The Doxorubicin and Olaratumab, on average, extended lifespan an average of just under 12 months. The medical oncologist also said much the same as you have above, that while the tumors shrink, they will not disappear and tend to come back with a faster rate of growth than initially seen.
At this time, my father has decided to go with the clinical trial with Durvalumab and Tremelimumab - NCT02879162. We are obtaining treatment at the Cross Cancer Centre in Edmonton, Alberta, Canada. The medical oncologist is Dr. Quincy Chu. He is part of a sarcoma group that regularly meets to discuss patient cases and treatment options and it appears he is active with immunotherapy drug trials and has had three patients enrolled in this trial thus far. (One patient remains in the trial on his 4th round. The other patients saw no benefit with this treatment.) My father meets with the doctor tomorrow to obtain final scan results, do final bloodwork and get the official green light to start treatment. If all goes well, his first treatment date is Feb. 15th. and every month after that.
While we pursue this line of treatment I am continuing to explore alternate therapies in the event this trial does not prove effective. I have signed up on Olga's forum and have left her a message inquiring about cryoablation in Canada. Although I understand that Cryoing 30 lung mets is likely not possible (especially with the primary tumor still present), I wonder if there would be benefit to cryoablate a few of the larger lung mets to see if there is either: a) an abscopal effect in the surrounding lung tumors or b) an ability to prolong life (and quality thereof) by eliminating the larger mets?
You mentioned that laser lung surgery may be a possibility. Aside from the Dr. in Germany, are you aware of any other doctors in the U.S. or Canada (preferably) experienced with this? Any names or recommendations are greatly appreciated.
Re: the primary tumor. There is no discussion of removal at this time. The medical oncologist has said that the drug trial is a whole body treatment, so hopefully if the trial proves effective, it would also have an effect on the primary tumor. If this is the case, he said we could discuss excision of the primary tumor at a later date. Unfortunately, the eligibility criteria for the trial stipulated the patient must have waited a period of 4 weeks from the last dose of radiation until the date of registration for the trial, must have recovered from previous treatment, be mobile, etc. (We are now 2 months from date of metastatic diagnosis to start date of treatment! Very frustrating!) That being said, I don't know if pushing for surgery with this Dr. prior to starting the trial would have been be wise, as the lung mets have shown growth in size and number in the 6-7 weeks between scans. Do you have any thoughts on this?
Thank you again for your comments and insight and most especially, your precious time.
Jamie
Hi Rene & Edward,
I hope this email finds you both well. I am looking for your opinion on the trial that we've previously discussed.
My father had his first treatment on Feb 15th. Side effects were manageable and minimal and he was feeling alright until this last week. Chest and left flank bursts of pain when laying down and standing up from a prone position were being experienced in increasing numbers. We went to emergency on the weekend, where blood work, an xray and a chest CT were performed. Blood work came back with slightly elevated white blood cell counts. The xray and chest CT came back showing an increase in number and size of nodules and moderate malignant pleural effusion on the left lobe (never noted on previous scans.) The verdict was that the disease is progressing and the fluid on the lung is likely causing him pain.
Fast forward to today's appointment with the oncologist.
The oncologist said that is was his experience that if the patient experiences tumor growth AND an increase in symptoms, then the immunotherapy is likely not working.
On the flip side, he said he has had cases where there has been huge tumor flare, but his clients typically feel better and have no/fewer side effects, only to find out the tumor has shrunk on the next scan.
That being said, the oncologist could not speak specifically to efficacy of these drugs with this sarcoma as it has no test group results as of yet.
The initial plan was: scan, treatment 1, treatment 2, scan (if there is disease progression continue treatment for one more month and scan again), treatment 3, scan again (if still progression then remove patient from trial).
At this time my father has had one treatment only. The early CT was only a result of the trip to emergency.
Due to the oncologists experience with side effects and tumor flare noted above, the oncologist gave us a few options:
- stop trial and start chemo asap (combination Doxirubicin and Olaratumab)
- continue trial, get treatment #2 tomorrow and scan again April 2nd. If there is growth between the scan last Sunday and April 2nd, withdraw from trial and decide whether to continue with the chemo option at that time.
Do you think that one treatment is enough to show whether the immunotherapy is going to work or not?
If the answer is no - would a scan 2 weeks after the second treatment be adequate time to allow for the immunotherapy to work? (1.5 months from first treatment date.)
Do you agree with the oncologist's comment that increase in tumor growth PLUS symptom increases as mentioned above is good indicator that the trial is not working this early in the process?
Your input is appreciated. I look forward to hearing from you!
Sincerely,
Jamie
I'm so sorry your father is in pain with the pleural effusion.
As for figuring out whether it's tumor flare or tumor growth, the stories of Mr. Telford and Jake are examples (Chp 10, section "Tumor flare or tumor growth?", pg 166-167).
I can't comment on whether increasing symptoms along with increasing size of tumor on scans indicates the immunotherapy is not working. I would imagine it depends on the time frame and the location of the immune response. I don't know if doctors/researchers have figured out how long to wait (After detecting "tumor growth", shrinkage was seen for Mr. Telford 2 months later, and 3 weeks later for Jake)
Also bear in mind that the immunotherapy combo your father is getting is a very strong one, so the immune response may be much stronger.
I personally would not give up so soon until I have irrefutable data about the status of the cancer.
I'm not sure if this will be helpful, but I recently gave an 1-hr lecture on immunotherapy to the general public. In one part, I cover how my last re-recurrent jaw tumor was confirmed by pathology to be tumor flare, and not a completely solid tumor mass. (https://vimeo.com/257984851)
Wishing you and your father the very best at this critical decision junction.
Rene & Edward, Thank you again for your insight and time.
The CT scan that was recently done while in the hospital was only 3 weeks and 3 days after receiving his first treatment of the combo Durvalumab and Tremelimumab.
Reviewing your book references, it does seem possible that it could be too soon for the immunotherapy to take effect.
My father did decide to move forward with the second treatment and received it on Feb 15th. He will be scanned again on April 2nd - 6 weeks and 4 days after his first treatment. We get the results of that CT on April 11th. Based on the results and his physical condition at that time (assuming he has not worsened), my father will be faced with the same decision - continue immunotherapy or cease the trial and potentially start chemo. ..... should there be further growth noted I will still wonder if 6 weeks and 4 days is then enough time for the immunotherapy to take effect?!
He is still experiencing increased coughing bouts, shortness of breath and positional chest pain. I believe this may be due primarily to the pleural effusion (as opposed to disease progression, which had also been noted) because the increase in symptoms came on very quickly. The oncologist has said that if the shortness of breath worsens, he should go to the hospital and have a pleurx catheter put in to drain the fluid. ... I wonder if it would be a good decision to put in the catheter sooner rather than later to potentially alleviate the increased symptoms? Do you have any insight into pleural effusions and/or catheters?
We also met again with the radiation oncologist. While she had said that further radiation could be done on the knee and potentially on one or two spots on the lungs, she said they would do it only to alleviate issues that may arise in the future, and that no studies have proven the efficacy of having radiation in conjunction with immunotherapy to create a possible abscopal effect and/or increase the efficacy of the immunotherapy with sarcomas. Essentially they are willing to be reactive and help to alleviate problems that arise in the future, but do not wish to be proactive and try something different to potentially slow down the growths as they stand currently. Very frustrating!
I have been in touch with Dr. Drewes at the hospital in Fuchkrankenhaus, Coswig regarding laser assisted lung surgery. (Thank you for the contact with Olga!) He has reviewed my father's scans and currently the mets are unstable, so he would not be able to operate. If they do stabilize in the future, my father may be a potential candidate for surgery at that time. ... so now we must find some treatment that will stabilize those mets. If you have any ideas or insight, I am open to all suggestions!
Thank you for your video link. I will certainly watch it!
Jamie
I personally have no experience with pleural effusion. But it is important to keep the symptoms and pain under control, so that they don't get in the way of the important treatment. One issue with a catheter is the possibility of infections. You'll need to discuss with the doctor to see the risk of that.
On that note, I just found out about the importance of the microbiome (bacterial flora) on the response to PD-1. "simply avoiding antibiotics while taking PD-1 blockers could boost patient responses from the current 25% to 40%" http://www.sciencemag.org/news/2017/11/your-gut-bacteria-could-determine...
But in the case where antibiotics are necessary to fight off an infection, probiotics afterwards may be able to restore the flora to assist in a beneficial response to the immunotherapy. We will post on our facebook page if we find other pertinent info (https://www.facebook.com/immunecure/).
Pneumonitis (inflammation in the lung) is a possible side effect with PD-1. The doctor needs to check carefully if this is the case, as steroids are usually given to calm down pneumonitis. It's been shown that the steroid doesn't interfere with the anti-cancer effect.
I'm glad you got in touch with Dr. Drewes.
Hoping for the best possible result, and wishing you and your father much strength during this waiting period.
I have (oligometastatic) UPS tumor as well. I am on the IPI/Nivo trial at MD Anderson on the Nivo arm and started radiation yesterday. I inquired about the dox/olar trial (olar is a targeted agent against PDGF) but did not qualify. They told me you needed to have had previous therapy, which I had not. Survival prolongation with this combo is what is expected, which was seen in a previous trial. I did not check this out for myself though.
Jlugg,
I am so very sorry to read that you have metastatic UPS as well. How are you faring with the radiation and treatment thus far?
In Canada, it is my understanding that Doxorubicin and Olaratumab was available without previous treatment. (The cost was approx. $13,000/treatment!) On average, trials showed it extended lifespan an average of approximately one more year. That being said, the medical oncologist also said that while the tumors may shrink, they will not disappear and tend to come back with a faster rate of growth than initially seen.
My father has decided to go with the clinical trial with Durvalumab and Tremelimumab - NCT02879162. We are obtaining treatment at the Cross Cancer Centre in Edmonton, Alberta, Canada. The medical oncologist is Dr. Quincy Chu. He has had three patients enrolled in this trial thus far. (One patient remains in the trial on his 4th round. The other patients saw no benefit with this treatment.) My father meets with the doctor tomorrow to obtain final scan results, do final bloodwork and get the official green light to start treatment. If that all goes well, his first treatment date is Feb. 15th.
While we pursue this line of treatment I am continuing to explore alternate therapies in the event this trial does not prove effective. A few avenues I'm trying to obtain more info on are laser lung surgery and cryoablation. Have you sought out either treatment at all? If you are willing to share, I would be interested to know more specifics of your condition and any treatments options you have tried or investigated. I would be happy to share any info on my end as well.
Wishing you the best with your treatment.
Sincerely,
Jamie
I am doing ok in terms of side effects with treatment and the radiation has been easy so far. Yes, I sought cryotherapy treatment at the Mayo Clinic, but my tumor was too close to the hilum of the lung to do that. Having said that, I would do cryo for any future lung recurrences. Mayo has lots of experience with that and they miht have some clinical trials coming up for Sarcoma. I don’t know much about laser lung surgery. I used to do cryo as a surgeon myself.