Cure Alveolar Soft Part Sarcoma International (iCureASPS)

In mid-dec 2008, my husband felt a lump in his right calf muscle. It was painless and was not really noticeable. He had no other compliants, but we thought we should get it checked anyway. Went to our general physician, he said he wouldn't want us to get worried but suggested that we get a biopsy done. We were referred to a surgical oncologist who did a FNAC and true cut biopsy. Both reports said "Alveolar soft part sarcoma" and this was December 24th and we were just planning to leave for a vacation. All plans had to be changed and he got admitted in the hospital for furthur investigation and resection of the tumor.

A CT scan of thorax and MRI of leg was done. The CT scan showed multiple bilateral nodules in the lungs, most of them were very small, largest being 1.3cms.
The surgery of primary was called off and he was started on chemotherapy. He underwent a surgery to place a chemo port. He has till date completed 3 cycles of ifosfamide(18g over 5 days) and adriamycin(130mg infusion over 96 hours). He has some side effects like fatigue, nausea and oral mucositis.

His follow-up is on 27th of Feb, he's scheduled for a PET CT scan and some blood work. We somehow want to push for surgery of the primary and if conventional surgery for lung is not possible(which is what the docs here feel), we want to pursue with Dr.Rolle. I have contacted Dr.Rolle and he was kind enough to respond immediately. He has asked for a CD of his CT scan which we are sending today. Hopefully, he will accept to do it. If Dr.Rolle can take care of the lung mets, our surgeon here is willing to remove the primary.

Its about 2 months since the diagnosis and its been difficult to make decisions at every step. Now that I here, I think I will post these queries and hopefully get your suggestions. For now, I will be very interested in talking to anyone who has gone to Germany for the laser resection of lung mets.

Hello... it's Kathy here. My husband Tom went to Germany for the surgery with Dr. Rolle and we would be more than happy to talk with you. My email is kathycoursen [at] gmail dot com and my phone number is 814 364 2144. I know all that you are going through and we would like to help in any way that we can....
Please take care,
Kathy

Thanks Kathy. I will contact you for more details.

Hi Arch,

I just got back from Germany last night. Our daughter 'K' and her dad are there - she had side 2 done with laser a week ago. She will stay there for another week and a-half for rehab. Please feel free (as well as any others who may read this post in the future) to email with questions. I am thinking of updating a page with more details with general information. There is no doubt Rolle has saved many lives as well as added years to many sarcoma patients.

Our daughter had conventional thoracotomy on one side and had we know what we known now, we would have gone to Rolle first. Her most recent surgery was on the conventionally operated side and he found many metastases within the staples...so the staples had to be lasered out. I do not blame the original surgeon as the pathology showed that he had negative margins around the mets he removed. But having a foreign body such as staples in the lung may make a nidus for microscopic met deposits. There are undoubtedly growth factors around the staples (they form granulomas, benign growths, by themselves).

We also had the pleasure of meeting another young mom (and her husband) from the sarcoma alliance board from Pittsburgh who was getting admitted.

If Rolle agrees, would definitely get that primary out ASAP.

Best wishes, 'F'

Some updates from here.

We had a follow-up PET CT scan after the 3 rounds of AIM chemotherapy. The primary in Sree's leg shows considerable necrosis. The lung mets have not changed in size or number. Only the biggest met(1.3cms) shows low grade FDG uptake, the remaining nodules show bare minimal to negligible FDG uptake.
Everything else in the full body PET CT scan is normal, so hopefully no other metastatic sites.

Sree was planned for resection of primary on the 27th Feb and we were waiting for Dr.Rolle's response on the resection of lung mets. I just got Dr.Rolle's response, he says a full resection of lung mets is not possible because the numbers are too many. He says there are too many very tiny mets. That is a major set back, I don't know how things will go from here.

If Dr.Rolle cannot do a full resection, is there any merit in trying to even do the best possible resection ? Any views? Any other way, we can deal with this kind of lung mets?

Thanks for all your suggestions.

If Dr.Rolle will agree to do a resection anyways even though there is no hope that it will be a complete resection, I would proceed with it because there is a chance that smaller metastases will be completely necrotic from the chemotherapy as it was described in the Dr.Nickerson case patient pathology findings after the thoracotomy. At least it will buy your husband a few years of life as they are a slow growing mets and when bigger mets are resected there might be a period of stability after that. Bigger metastases have the immuno supressive properties by themselves and might be a source of the secondary dissemination. He might also have a second round of resection in a few years if needed to be able to wait until the systemic cure might be found. If a conventional chemotherapy is done and the necrosis is incomplete there is a very dangerous consequence of it - conventional chemotherapy given at the MTD (maximum tolerated dose) as a side effect causes an increase in the vascularization and an increase in the blood supply to the metastases. It means that even partially necrotic metastases recover as a time goes and start to grow faster. Smaller ASPS metastases have almost no blood supply (and this is the reason they are not seen on the PET scan) so generally bigger ASPS mets need to be removed after the conventional chemotherapy.

Really appreciate your quick response. When I feel I am cornered,your reply gives me some direction in which I could proceed.
Thanks a ton.

Also check out the section under success stories in the Board index. There have a been a very few very long survival ASPS patients who had reached the point of heavy lung metastases. Because tiny lung mets seem to be avascular, they may be harder to kill outright with some of the new anti-angiogenesis agents. It might be they may need to get a little bigger before they respond - but I think I remember at least some small ASPS lung mets seemed to shrink in one of the patient cases in the Sutent paper.

There are a few cases in our forum who seemed to have small lung mets that went away with treatment - it seemed as though what they had in common was sustained chemo - more in the metronomic rather than short intense course type. It might be one needs to treat at lower dose for longer to kill slowly dividing cells. Also by not going off on the medication for a year, it avoids that backflash of angiogenesis that one can experience after courses of AIM for instance. I found it interesting Amanda's mother said that her oncologist wanted her to continue on Celebrex for awhile after coming off Vinblastine to avoid putting her body "into shock." Amanda had Vinblastine and Celebrex (both commercially available) and the recent Greek case report was Vinblastine and Cytoxan (also available). Looking at the CT in that case, it looked like there were some definitely small mets that could have not been taken out surgically. He is now 6 years out apparently NED. So maybe the low dose Vinblastine and Cytoxan killed them? I sent an email to the author (in English as well as Greek), but haven't heard about some questions I had.

Let me know if you would like this Greek paper (I also have the recent Sutent paper) and could send them to you by email - you could send to your doctor and discuss. The Greek case is in an 11 year old child though.

We are planning to low dose metronomic chemo (Cytoxan + Vinblastine) after 'K' comes back from her surgery next week with the hope that it may help kill some of the small ones or at least make them more dormant. Metronomic always made sense to me because of the slow dividing time of the tumor, but the Greek case was the first published report that I'm aware of.

Also do not lose heart. Things are moving more rapidly in the molecular and treatment side of ASPS. There could be significant benefit of even stabilizing the disease even if you do not kill off most of the tumors since many new drugs on the horizon also have significant promise of benefit in ASPS. Also most studies are looking at anti-angiogenesis agents one at a time...now there is a thought that combining these selective agents might have more beneficial effect.

To my knowledge, all long term survivors always had their primaries removed, though. There is an idea that the primary is releasing new metastases. Lung mets are in terminal vessels, so they may be less likely to spread (but still might by their vascular supply). If you could find any surgeon who might be willing to do it, it still might be worth proceeding.

Thanks 'F' for your reply.
Hope 'K' is doing fine after her surgery. Thanks for letting me know about metronomic chemo, I had read about it somewhere but sometimes it becomes so difficult to analyse what is relevant and what isn't. I would like to know how this has helped other ASPS patients, especially ones who have had very small, extensive lung mets as is the case with Sree. Please send me the greek report that you have talked about in your post, my mail-id is achugk@yahoo.com.

In the meantime, Sree's doctors think that he has responded well to AIM chemo, they have resected his primary tumor yesterday. The surgery went well, the surgeon told me that he has taken everything out with a margin. We have to wait for the lab results to know that for sure. After he recovers, his doctors feel that we should still request Dr.Rolle to resect his lung mets even if a full resection may not be possible and try some systemic treatment(I will discuss with them if metronomic chemo can fit in here).

Arch - would you be able to look in the pathology report from the resection of the primary tumor - what does it say about the % of the necrosis and if they think it is a spontaneous necrosis (that is located in the center of the tumor and is cased by the insufficient access of the blood supply in the center of the tumor and is a frequent event in ASPS tumors especially when they are large) or a chemotherapy induced necrosis (I am not sure if it is possible to tell one from another). Is Sree continued with the chemotherapy?

Hi Olga,
The pathology report says there is some necrosis, I am not sure where it is or the % of necrosis. I will ask for a more detailed report and discuss with the medical oncologist to understand how effective the chemo was. The surgeon was happy to see that the margins were all clear.

Sree had his primary removed 17 days after his 3rd round of AIM chemo. He is not on chemo now, apparently, we are waiting for him to recover from the surgery. I'm not sure how safe it is to wait like this. Any thoughts? We also want to discuss with our doctors about the possibility of some other systemic treatment, sutent or metronomic chemo untill we find someone to operate his lung mets.

I don't know whether it helps or not, but this time after 'K''s second thoracotomy, we restarted Celebrex 400 BID on day 4 postop. Celebrex has been used safely for post-op pain. There is a little literature suggesting its use postoperatively might reduce tumor growth -

http://cancerres.aacrjournals.org/cgi/c ... /64/9/3230
http://www3.interscience.wiley.com/jour ... 1&SRETRY=0

We did not feel comfortable using any stronger anti-angiogenic agent because some angiogenesis is necessary for the heailng process.

Hi 'F', Read the link that you have sent, it seems so logical to be on some systemic treatment during post op period. I have sent it to my doctor and asked for his opinion.
Has anyone else also taken celebrex post surgery when chemo or other stronger anti angiogenic drugs cannot be taken ?

I also see that you have done quite an exhaustive molecular profile of 'K''s tumor.
I don't think its routinely done, I was wondering if I should ask for it so that we might be able to choose more appropriate treatment atleast in the future.

As always, thanks for all your resourceful updates.

The molecular profiling is controversial because some people believe that the tests have not be shown to have a definite predictive value. In one person's previous case in our forum, it was said profiling led the doctor to choose a particular agent, but ultimately that medication did not work, and the patient went on to have a deteriorating course. I suspect that that one case soured others on the benefits of profiling, but based on the results I could see (and knowing the signal transduction pathways), several drugs could have been considered and there was not especially strong support for the drug ultimately chosen. Also that drug was new and subsequently it was found to have immunosuppressive qualities that probably weren't a good idea in ASPS. So the decision is a complex one.

FYI, the recent sunitinib paper actually did quite a lot of testing on their five or so ASPS cases, and if you aren't able to profile your husband's particular tumor, it might be that those findings can still help guide decisions re: clinical trials. In general 'K''s profiling matched this - with some differences here and there. We also had a charitable organization picking up the tab (whatever insurance didn't pay) and we became friends with the pathologist at UCLA, so it helped with the ordering of tests. I can't say it has overwhelmingly been beneficial so far, but it put certain drugs in the preferred and non-preferred groups -and so we think it has been helpful enough for us. We also learned about the heterogeneity of the tumors (for instance high met and COX2 in the primary, negative VEGF, COX2, and met in small new lung metastases, high VEGF & PDGF in large lung mets), that made us more likely to go to surgery if systemic medication didn't work, also to reach for the VEGF/PDGF factors if we hav larger tumors and become non-resectable at some point.

The problem about these clinical trials is that there is a significant investment going into them, staying on them etc. And when you're on them, you usually can't be on anything else. We didn't like acting completely blind...that is without any specific knowledge from 'K''s cancer...but that is what most people do. It is possible like I said our results have not helped that much, but it seemed to guide us at least to avoiding certain trials that didn't seem promising at all.

Significant players identified so far in ASPS (that have promising investigational agents) seem to be PDGF, VEGF, and probably met and COX2...although the latter two may not be so important with tumor growth in later stages.

To add my two cents - as 'F' said there is a significant heterogeneity of the tumors in the same patient and organ specific too so if you want to try to do a profiling for the lung mets treatment it is better to do a profiling of the lung mets, not the primary. So generally you need a tumor tissue from the lung mets which can be taken by VATS as a sample for the profiling if the surgery will not be possible by some reason. Also a few lung mets need to be taken with the range of sizes to provide a sample for the small size mets 2-3 mm and for the bigger mets (bigger then 10 mm? I do not know when they turn the angiogenesis switch on).