Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Dear Johannes,
This is WONDERFUL!! news and I am SO VERY happy for Elisa and you, and so deeply grateful for your thoughtful sharing . If I am correct, Elisa has now been on Cediranib for about two years with continued stable disease which is a great victory with this very challenging disease, especially since Elisa still has her primary tumor which is thought to be a deterrent to systemic treatment success due to the increased tumor burden in the body.
I am so sorry that you are facing such a difficult decision regarding resection of the primary due to the difficulty of the surgery which could heartbreakingly negatively impact Elisa's quality of Life. This is certainly a very important consideration and one which I know needs to be weighed very carefully especially since Elisa has been able to attain disease stability on Cediranib despite still having her primary. Does Elisa experience any pain or debilitating impact on her physical movement as a result of the primary? I will be anxiously awaiting your update regarding the surgeon's recommendation following his meeting with the Tumor Board, and my most special thoughts and very best wishes will be with Elisa and you as you try to make the best decision on this difficult issue. Of course a huge concern and consideration will be the amount of pre-op and post-op time that Elisa would need to be off of the Cediranib to prevent dangerous hemorrhage from the surgery, since there is a known risk of rebound when Cediranib is discontinued. As you said so well, it is all "about balancing the probabilities" which is so difficult to do.
Sharing the special joy of Elisa's good scan results with deepest caring and continued Hope,
Bonni

Hello,

There is – again – not much news regarding Elisa’s participation in the Cediranib trial. According to the oncologists, last month’s scans showed that everything is stable.

Since Elisa has been participating in the trial for over two years now with very stable side effects, we had been asking for a while now whether she could extend her visits to the NIH/NCI to two months. And after a lot of back and forth, this request has been approved! Perhaps this might be of interest to other participants…

Besides this, the doctors were again fairly optimistic about Cediranib eventually receiving FDA approval and being commercialized. Even if AstraZeneca has stopped the development for now, it would probably resume production in case of an approval. And otherwise, the drug would apparently not be very complicated to produce, which means that another company could easily take over.

Wishing you all the best,
Johannes

Dear Johannes,
Thank you so much for sharing this VERY good and encouraging news about Elisa's continued and long term disease stability , and also regarding the potential for the continued development and production of Cediranib. Is Elisa also having continued shrinkage of her primary tumor in her leg in addition to the stable disease, and has any decision/recommendation been made regarding resecting the primary?
Because of Brittany's long term sustained stability, several months ago we were also able to receive permission/approval to extend her Clinical Trial visits to Edmonton to once every two months instead of the previous monthly visits which had been required by Astra Zeneca and the Clinical Trial protocol. This has relieved a huge flight and accomodations expense burden, and greatly reduced the physical fatigue and stress on Brittany of having to travel to Edmonton from Seattle once a month.
I am so sorry, saddened, and disappointed that you have not received any other comments of caring and support on your thoughtful posting because shared support and encouragement from other ASPS Community members is so very important and strengthening, and has always been an inaluable and integral part of this Forum. I Hope that you don't get discouraged by the lack of responses, and that you will continue to post and share since the anecdotal treatment information that you and others graciously share on this Board provides a critically important and powerful weapon for all of us to better fight this poorly understood disease because knowledge is power.
Please give Elisa and yourself special congratulatory hugs from me, know how very much I am sharing the joy of Elisa's continued stable disease and successful response to the Cediranib, and know how deeply I care.
With happy hugs, special caring thoughts, healing wishes for Elisa, and continued Hope,
Bonni

Yes, cediranib made Elisa and Brittany's continued and long term disease stability , like a ray of dawn in the dark , give all ASPS patients with hope! Thank you Elisa and Johannes！thank you Brittany and Bonni！ your long-term up-to-date posting for me and other ASPS patients is Extremely valuable.

Dear Feng zhou,
Thank you for your very kind words, and for your special support and encouragement which is so deeply appreciated. My special thoughts and very best wishes continue to be with your dear son and you, and I will look forward to a Board update from you about your son's current disease status and treatment when your time allows.
With deepest gratitude for your thoughtful post, and with special caring thoughts, healing wishes for your son, and continued Hope,
Bonni

Hello,

It’s been a while – again! - that we haven’t updated the board on how Elisa is doing. Unfortunately there have been some changes. This week Elisa made her last visit to the NIH/NCI. Since the CT scans done on Monday showed again some growth, she apparently hit the magic 20% target and was removed from the study. Of course we were expecting that this would happen, sooner or later. But it was still quite a shock, especially since the doctors at the NCI had always been very confident and had attributed the “minimal growth” indicated in the previous reports to the usual margins of error and had told us that there was really nothing to worry about… She was sent home with the very brief recommendation of trying Pazopanib or Sutent or some T Cells - trial (is anyone familiar with the latter???). The way Dr Kummar handled this situation and the total absence of emotional support from the team (which team??? even the clinical nurse suddenly disappeared) was disappointing and extremely frustrating. Anyway, this is just to let other participants in the trial know what (not) to expect.

The CT scan reports are also not very detailed, speaking of “mixed changes in bilateral pulmonary nodules with some stable others slightly larger. For example, a left lower mass now measures 2.7 x 1.8 cm, previously measures 2.4 x 1.6 cm.” The report also notes “slight internal enlargement of a 3.1 x 2.0 cm right external iliac enhancing mass”. This was, I think, previously referred to as “right external iliac lymph node” or “right external iliac adenopathy”, already noted before Elisa started the trial but sometimes not even mentioned in the reports later on. I am not sure to what extent we should be concerned about this mass/lymph node. We don’t even have the final report of CT of the primary in the thigh yet; the preliminary report speaks of a “soft tissue mass unchanged”, although the doctors at the NCI told her that it had grown by several centimetres.

Altogether, my feeling is that we are sort of back to where we were before Elisa started the Cediranib trial two and a half years ago. This is of course rather frustrating – by the way she has been doing really good lately, going for a 45 min – jogging three times per week, etc.

We will of course discuss treatment options with her oncologist very soon; if you have suggestions in the meantime, you are all of course more than welcome.

With my best wishes to everyone,
Johannes

P.S. Since Elisa is not in the Cediranib trial any more, we will post from now in the regular personal update section.

Thank you for an update on Elisa's experience on cediranib. It is a very unfortunate that the tumors developed resistance and cediranib has stopped working. It also looks like the NCI staff people have developed resistance to their patient's pain and their compassionate ability also stopped working.
I would try to resect the primary. Then she can be evaluated for the resection. If it is not at all possible (you should get few surgical opinions) than the cryoablation of the biggest nodules might be possible, I would get evaluated before starting any other TKI as when she is on them, she can not have either - surgery or ablation.

Dear Johannes,
Thank you for your thoughtful, but very heartbreaking update. I am so deeply sorry and saddened about Elisa's disease progression which has resulted in her being abruptly taken off of the Cediranib Trial. I am also very sorry, but unfortunately not surprised, about the abrupt, dismissive, and uncompassionate treatment that Elisa and you received from Dr. Kummar and the NIH Clinical Trial staff. Disgustingly and inexcusably, several other ASPS patients who previously participated in the NIH Cediranib Clinical Trial were similarly negatively treated once they developed disease progression. I am abhorred by not only their cold hearted personal treatment of Elisa and you, but also by the erroneous, deceptive, and vague radiologist reports.
I don't want to frighten you Johannes, but I am especially concerned right now about Elisa's risk of rebound and rapid disease progression since she was so abruptly taken off of Cediranib, as devastatingly occurred with Jonathan Guay following his similar sudden dismissal from the NIH Cediranib Trial for what inexcusably turned out to be erroneously reported tumor growth. Tragically, Jonathan lost his couragous battle a couple of months after being taken/forced off of the Cediranib. If you are interested, I will give you Jonathan's mother Beth's e-mail address in a private message if you would like to contact her regarding this issue. Did Dr. Kummar even discuss the risk of rebound with Elisa and you and provide any advice regarding this documented concern?
I agree with Olga that removing the primary is very important, if resection of the primary is possible, and should probably be pursued immediately, and before beginning another TKI treatment. This will help to reduce Elisa's body's tumor burden and Hopefully enable any future systemic treatment to be more effective and successful. There is an urgency in moving forward as soon as possible with whatever treatment choice is made to try to prevent the rapid post Cediranib disease progression that tragically occurred in several other ASPS Cediranib patients.
I so deeply share Elisa's and your great heartache and disappointment for her developed Cediranib resistance and disease progression, and your frustration about the shameful uncaring treatment you received from Dr. Kummar and her Clinical Trial staff. Please take care Johannes and know that I am holding dear Elisa and you very close in my heart and most caring thoughts, and am here to try to help in any way that I can with shared information and support.
With deepest caring, special hugs, healing wishes for Elisa, and continued Hope,
Bonni

Dear Bonni and Olga,

Thank you very much for your kind and thoughtful replies.

Elisa raised the issue of a possible re-bound effect several times at her appointments, but last time because she had not taken Cediranib for one week right before her appointment (there was no Clinic on the day after the usual 8-week cycle, so she went after 9 weeks). Elisa argued that this might have had an effect and, at least partly, explain the growth. But this argument was not taken seriously, and Dr. Kummar just said that a re-bound effect would not materialize so quickly. Anyway, my feeling is that a possible re-bound effect is no what the Clinical trial team worries about, since this can only happen once patients are off the trial...

We are, of course, again thinking about resection(s). It does make sense, especially in the long term, to plan resecting the primary and perhaps also have as many lung mets as possible removed (I sent an e-mail to Dr. Rolle today to see what he thinks). The problem is that the primary is very large, and it would be a major surgery with a long period of recovery. Elisa is doing so great these days; she is very active and can lead a healthy lifestyle, and it would certainly not be helpful if her quality of life decreased (possibly in the long term, as cautioned by the surgeon), because of this surgery. My concern is not only that during this period we would not be doing anything to keep the lung mets under control, but also that she might have less energy afterwards to fight the disease.

I agree with you that it would be very important to continue a treatment without further delay. Elisa has already been contacted by a nurse from GlaxoSmithKline regarding the Pazopanib patient support program, and apparently things look good. My sense is that if she can get on Pazopanib soon, we'll probably try that and hope that this can, again, shrink the tumors. Based on some recent but admittedly early studies (e.g. http://www.ncbi.nlm.nih.gov/pubmed/22585997: the logic is that an anti-VEGF treatment increases c-Met activation, which is why a simultaneous inhibition of VEGF and c-Met signalling might be more effective), I would have liked to have Elisa try a combination of Pazopanib with a c-Met inhibitor such as Crizotinib (the simultaneous blocker XL184/Cabozantinib is not available). But her oncologist doesn't think it's a good idea...

Thanks again and best wishes to all of you,
Johannes

Dear Johannes,
Thank you for the additional information. Sadly, I think that you are right in your feeling about Dr. Kummar and her Clinical Trial Team not being concerned about re-bound effect because they apparently don't even follow or keep in contact with the patients who have been taken off of their Trial since the patient is no longer of any use to them as a "guinea pig" or "lab rat" which certainly seems to demonstrate a cold hearted attitude and lack of personal caring and compassion. It is so shocking, ridiculous, frustrating, and inexcusable that no patient followup is done since critically important and invaluable information could certainly be gained about post treatment effects and outcome.
However, Dr. Kummar was probably correct that Elisa's one week absence from the Cediranib was not long enough to account for the 20% increased growth of her mets. Brittany was off of Cediranib for a two week period (one week pre-op and one week post-op) to prevent hemorrhaging when she had her superficial abdominal met resected and it thankfully did not seem to cause any detectable increased tumor growth or disease progression. Also, during Brittany's severe vomiting episodes, she is usually off of the Cediranib for about five days until the toxic effects of the drug have been alleviated, and thus far, she has thankfully not experienced any re-bound from her short term discontinuation of the drug. I would encourage you to contact Beth Guay (send me a private message if you are interested in having her e-mail address)) to find out from her how long Jonathan was off of the Cediranib before he experienced his re-bound and tragic rapid disease progression so you might have some idea about a possible timeline for the occurrence of re-bound.
I understand your dilemma about resection of Elisa's primary since she would not be able to be on a systemic treatment pre and post surgery which could possibly put her at risk for disease progression. However, the benefits of removing the primary could outweigh the risk of not being on a systemic treatment since removal of the primary often results in stabilization of the disease for awhile and it certainly reduces the body's tumor burden therefore strengthening the immune system and allowing a systemic treatment to be more effective. Before Brittany had her small superficial abdominal met removed because it was "not being a team player" and was continuing to grow a couple of months into her Cediranib treatment, she was having very little if any tumor shrinkage which was concerning Dr. Sawyer, but once the abdominal met was resected, she thankfully began to have dramatic tumor shrinkage and disappearance of her remaining multiple and widely disseminated mets.
Did Elisa have any shrinkage at all of her primary tumor while she was on Cediranib? If not, or if there was only a small amount of shrinkage, it may be because the tumor is so large and it interfered with the effectiveness of the Cediranib as unfortunately may also happen with any other kind of systemic treatment.
It is my understanding, and Olga or Ivan can correct me if I am wrong, that Dr. Rolle will not accept patients for lung laser resection of they have any other tumors anywhere else in their body so unfortunately this might prevent Elisa from being able to have her lung mets removed by him as long as she still has her primary.
If Elisa does decide to move forward immediately with Pazopanib treatment instead of resection of her primary, according to Dr. Sawyer and other information that I have read, there is apparently some evidence that if a patient develops resistance to one type of TKI such as Cediranib, switching to another TKI like Pazopanib can often result in re-stabilization of the disease.
Whatever decision Elisa and you make, please know that my very best wishes and most positive thoughts are with both of you Johannes, and I will be anxiously awaiting your next update. Take care and give yourself and Elisa warm hugs from me.
With deepest caring, special thoughts, healing wishes for Elisa, and continued Hope,
Bonni

Dear Bonni,

Thanks again for your reply.

Elisa did have very signficant shrinkage of her primary tumor (this is what probably caused the tumor pain at the beginning of the treatment). Although the decrease is difficult to express in numbers, the tumor was at same point described as being half as big as it used to be.

I totally agree with you that one week off Cediranib should not cause a rebound effect. The mets had certainly not grown only over the past two months, but the team of the clinical trial had never been specific as to the amount to which they had already grown... so that's why it ended up being a bad surprise last week.

I also hope that switching to a similar but slightly different TKI-inhibitor might actually turn out to be more effective.

Anyway, I'll keep you posted. Thanks,
Johannes

I just want to confirm that it is true, Dr. Rolle does not usually accept patients for lung laser resection if they have the primary intact.
It is good that you contacted Dr.Rolle - I hope you sent Elisa's CT scan on a CD to let him to review it - so you would know if he sees the resection possible at all, it will be helpful for the overall planning.
There is a tactical advantage currently that Elisa is already off the TKI for awhile so she might proceed with the primary resection right away, otherwise if she goes on the pazopanib and has a progression detected at some point, she will have to wait for the wash out period before being able to have a surgery, in the meantime the lung mets might overgrow the resectable size or any other metastatic sites might appear to put a stop on the surgery plans. I suggest you to consult few best ortho surgeons to minimize the risk of the surgery being detrimental for Elisa's quality of life.

Dear Johannes,
Thank you for the additional information clarifying that Elisa actually did have some significant shrinkage of her primary tumor when she was on Cediranib. This is very encouraging and provides Hope that a different TKI like Pazopanib may also be successful in helping to shrink her primary if she opts not to have it resected prior to beginning a new systemic treatment. However, Olga made a very good point about the "tactical advantage" of having the tumor resected prior to beginning Pazopanib since Elisa has already been off of the Cediranib for the amount of time that would be required pre-op, and once her primary is resected she may be eligible for laser resection of her lung mets with Dr. Rolle which would dramatically reduce her body's tumor burden and help to strengthen her immune system to better fight this very challenging disease.
Elisa's and your very frustrating and inexcusable experience of being suddenly surprised by Dr. Kummar and her staff with the unexpected news that there was now 20% growth of Elisa's mets, when the mets had actually been slowly increasing in size over many months, is a prime example of why the scans need to be visually compared and reviewed by the radiologist, the oncologist, and the patient with the original scans done prior to treatment was begun so that the actual amount of increased growth, if there is any, can be observed, documented, and closely followed in subsequent scans so there are no sudden surprises like Elisa and you heartbreakingly experienced. Just comparing the scans with the immediately previous ones is not adequate because over a period of time small amounts of increased growth accumulate to become large amounts of growth. Also, just naiively accepting the conclusion of the written radiologist report without personally reviewing the scans can result in disastrous consequences as devastatingly occurred when the radiologist failed to record the presence of Brittany's clearly visible spinal met in two consecutive three month scans, and the tumor continued to grow until it became symptomatic and then required two emergency major spinal surgeries which threatened paryalysis and resulted in Brittany now heartbreakingly suffering severe and chronic debilitating spinal pain.
I know that Elisa and you are facing some difficult treatment decisions, and my heart and most caring thoughts are with you Johannes. Please take care and keep the Board updated as your time allows.
Reaching out across the miles to share warm hugs, deepest caring, healing wishes for Elisa, and continued Hope,
Bonni

Hello again,

I completely agree with you - comparing images is very important. Elisa's latest CT scan reports even indicated some growth, but when we asked the trial team about this, we didn't really get any more details ("nothing to worry about...").

We are still thinking about what to do, of course. We'll send the most recent scan results to Dr. Rolle to check whether a laser OP would be an option, although the primary would have to be resected before that. Elisa saw another oncologist, who is also a sarcoma specialist, a few days ago, and he suggested trying traditional chemo now. I guess the logic is that after a TKI-treatment chemo might work better. Perhaps this could be related to the possible re-bound effect - the tumour cells grow faster than usual in this period and may therefore become a good target for chemo!? I am not really convinced. At the moment, it looks like we'll rather go for Pazopanib, which should be provided by GSK (not confirmed yet).

I know that Tok, like a few other board members, did respond to chemo. Could you confirm my impression that this always happened only after local treatment/surgeries? Do you see a link here? Thanks again!

I wish you all a great weekend,
Johannes

Hi Johannes,
I'm sorry that I don't have answers for your questions, but perhaps Olga with all of her incredible knowledge and expertise may have. There remain so many unknowns, unanswered questions, inconsistencies, and individual responses with ASPS that all we can do is continue to actively and aggressively research and network with other ASPS patients and their families to try to determine what seems to be the most typical behavior with this very rare disease, and what treatment approach and treatments seem to offer the best chance of successfully managing and controlling it. While traditional chemo has been thought to be, and mostly proven to be, an unsuccessful treatment for ASPS, there have certainly been a couple of very happy and successful exceptions including Amanda Minderlein and Tok. The theory that traditional chemo might work better following TKI treatment because of faster growing tumor cells caused by rebound sounds good in theory, but I don't personally know if this theory has ever been tested or proven. Does the sarcoma specialist who suggested this approach to you have any documented data to substantiate his recommendation? What were his thoughts/recommendations on resecting Elisa's primary prior to beginning any type of systemic treatment whether it be traditional chemo or Pazopanib?
I continue to wish/Hope that more ASPS patients or family members of patients who are currently taking Pazopanib will participate on this Board to share their Pazopanib treatment experiences and results as you, I, and others have done about Cediranib. We all need this invaluable shared anecdotal treatment information to make the best possible treatment decisions since it can take years before study data and results are published, and unfortunately this insidious disease does not usually afford us the luxury of having years to wait to get the published information regarding the success or failure of a treatment. Although the couple of ASPS patients who I am personally aware of and follow who are currently taking Pazopanib or their family members are unfortunately not sharing any information on this Board, I would be glad to share their names and contact information with you privately so that you can contact them to discuss their Pazopanib experiences and results if this would be helpful to you in making the decision about Elisa possibly starting treatment with it.
I Hope that you and Elisa are enjoying a good and relaxing weekend, although I know that is difficult when you are trying to make difficult treatment decisions. My continued deepest caring and best wishes are with both of you, and I will be anxiously awaiting your next update.
With warm hugs, special caring thoughts, healing wishes for Elisa, and continued Hope,
Bonni