Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Olga and any others, please add your comments on this post. Is this an accurate summary of the common features of ASPS patients with lung mets who seems to have a complete remission / cure?

From what I've been able to review here and case reports: all patients who have been cured of stage IV ASPS (primary + lung mets), they all had the following in common:

1. Primary out.
2. Sometimes pre-thoracotomy chemo
3. Thoracotomy on one side
4. Thoracotomy on other
5. Chemo x 36 weeks to 2 1/2 years (prolonged).

The cases include 2 case reports:

1. (Nickerson article in your library): 13 year old - no evid disease 10 years out from diagnosis - primary out, 2 cycles chemo (12 weeks), thoracotomy 1, thoracotomy 2, 36 weeks of chemo.
Agents: vincristine, cytoxan, mens, doxo; alt with etoposide, ifos x 6. Surgery removed 13 nodules L, 11 on R.

2. (Baum: http://www3.interscience.wiley.com/cgi- ... 1/PDFSTART) 14 yo - no evidence disease 5 years from diagnosis-
primary out, thoracotomy 1(40 mets), thoracotomy 2 (52 nodules), 2 years of outpatient chemo. vincristine, actinomycin D, cytoxan, doxorubicin.

3. Camilla - 24 years from diagnosis-
primary out, chemo, thoracotomies, chemo x 2 1/2 years.
adria, cisplatin, DTIC

4. Tammy - 22 years from diagnosis-
primary out, XRT, chemo, thoracotomies, chemo
vincristine, actinomycin, cytoxan, adriamycin, cisplatin

5. Amanda - 6 years from diagnosis-
primary out, thoracotomies x 2, recurrence of mets, chemo.
celebrex + vinblastine x 8 mos, celebrex x 1 year, 3 rounds of ? AIM

Radioablation, VATS etc seems preferable to thoracotomy, but the risk is that thoracotomy may be a better way to increase the risk of cure. The other thing I notice looking at this list is how long chemotherapy needed to be given. There is a lot of interest in metronomic chemotherapy - lower daily doses of chemo that is better tolerated and may improve the kill of slower dividing cancers like ASPS.

When I look at the above, I'm thinking it supports being aggressive early - certainly in terms of duration of chemo - if a complete cure is hoped for.

Good job systematizing the data. We do not have any long term survivors with the multiple lung mets who didn't have chemo and the duration seems to have something to do with it, I have this wild idea that it doesn't work like the cytotoxic as it shouldn't be working in slow growing tumors but affects the production of something this tumors needs to grow so finally they commit suicide. We even had a girl on the former web-site with lung+liver mets who was on a single agent Gemcitabine for 18 month (it was a clinical trial back then 3 weeks on a week off) and her liver mets started to regress after 6 month of treatment, then lung mets mostly gone and there were a few persistent and she had them surgically removed in the end and was cancer free a few years after - another anecdotal experience.
Bur chemotherapy without the surgery to remove the residual mets is not a good option as it never 100 % effective and mets are only partially necrotic and after they recover they start to grow faster, so I would not go for the chemo if there was no commitment from the good surgeon to do a resection. Some surgeons will not resect primary if there are lung mets and practically no thoracic surgeon will resect lung mets if there are still a primary, but I think at the MSK they do resect both.
Reg. the place of ablations for lung mets treatment - my firm belief is that it has to be used exactly as it is officially positioned now - when there is no surgery possible, in lieu of other options as if we start from the ablation it will affect the quality of the thoracic surgery if it needed later (and it is always done at some point with the ASPS lung mets). There are a lot of adhesions and scarring after the ablations and VATS and they bleed a lot when pleura is separated from the lung for the surgeon to palpate. Also there are usually much more mets is found on the open surgery esp. if it is done as the first treatment - clean lung surface, better chance for the surgeon to find more mets. So I would start from the best avail. thoracic surgeon first.

Thanks very much for your input on this, Olga. Gives us much to think about. And more waiting to see what decisions the surgeons will make. First step for us is the primary, but we have to find a willing thoracic surgeon as well.

The different stages of metastases almost certainly have something to do with this. At least in other cancers, 1-2 mm mets are often avascular. Once they become vascularized, they may be more susceptible to having some cells killed. Antiangiogenesis agents may be regardless of the fact they may not be able to kill the tumor though because they may keep the tumor from getting beyond a certain size, getting more growth factors from the circulation, and forming more vessels that would allow it to spread.

Also in the case of ASPS, the slow doubling time must have an effect on why it is so difficult to eradicate. If the doubling time for the tumor is 60-90 days and an agent like vinblastine is being used, the cell has to incorporate it into its dividing machinery to get killed. If it is not given long enough, there's no chance it can have an effect. The cells are sitting there dormant - alive, but not dividing.

I wanted to update this thread after our discussion with our oncologist Doug Hawkins yesterday.

Another confounding variable to consider are advances in imaging since ASPS cases starting getting recognized. The MD Anderson study (Portera) is from 1959-1998, the Kayton study (Sloan Kettering) is 30 years. I am sure that what some people thought was no evidence of metastases decades ago, would be multiple mets by some of the more sensitive methods today.

I found this 2001 poster by Judson (UK): http://www.ctos.org/meeting/2001/posters/poster58.html
that found:

"Local recurrence was rare (1 patient) but 74% of the patients (14/19) had developed metastatic disease. 47% (9/19) had pulmonary metastatic disease at presentation with 26% (5/19) developing metastatic disease more than 3 years after diagnosis. At last follow up, 69% (13/19) were alive, 32% (6/19) were disease free and 37% (7/19) were alive with metastatic disease. No objective responses to chemotherapy were observed in the 47% (9/19) of patients who received chemotherapy for metastatic disease but of the 9 who underwent pulmonary metastasectomy, 7 achieved complete clearance, with only 2 of these recurring in the thorax after surgery. 4 patients of the 9 (44%) remain disease free at last follow up."

The success rate of surgery alone seemed much better than I would have expected, but I still wondered what he thought now of chemo. I sent a post-Christmas email out to Dr. Judson and he was kind enough to answer quickly. He said the only agent he would recommend now is Sutent.

We also learned about a new technique by a recently recruited pediatric surgeon at the UW (Kenneth Gow) which involves VATS and ultrasound to detect small tumor nodules. Apparently he has been able find and remove deposits as small as 0.5 mm, and he believes it is more sensitive than detection by palpation alone.

We still have uncertainties before us, but we are contemplating a course of primary out, then this VATS-US procedure (he calls MITUS), and possibly a follow up course of fairly well tolerated metronomic chemo (e.g. may be celebrex + vinblastine). After I sent Doug the case reports, he emailed a friend of his who was one of the authors of the paper of the case report endorsing intensive chemo in ASPS, and interestingly she said, she probably wouldn't do this intensive chemo today. This is the dilemma with case reports and literature! Docs don't publish their negative data (when the treatments don't work).

I hope I haven't just confused everybody. For some people more information is worse, but even through all this mess, it helps me feel like I'm better informed.

When I get a chance, Olga, I'll post what data I've been able to extract in the event it might help the decision making of others. Blessings to everybody.

I would like to see the full text of the presentation with the tables as phrase like this "No objective responses to chemotherapy were observed in the 47% (9/19) of patients who received chemotherapy for metastatic disease but of the 9 who underwent pulmonary metastasectomy, 7 achieved complete clearance" makes me wonder - the people who achieved the complete clearance - did they only have a surgery or a chemotherapy and a surgery in addition?

No objective responses to chemotherapy in lung mets is the usually seen outcome if the surgery is not follow, but at times mets which didn't change in appearance and size for awhile can slowly dissolve after a prolonged period of time - month or even years. I think they might be necrotic but very slow to dissolve.
And what was the period of observation. "at last follow up" is usually a 5 years length. I more interested if there was any information on the long term surgical remission (more then 10 years survival with no cancer related events - no mets anywhere). We only have long term even free survival cases for chemo+surgery documented (Dr.Nuckerson - and I contacted him and he supports chemo as he has found necrosis in the resected lung nodules) and anecdotal (Camilla, Tammy - people who are here now so they are getting the contemporary scanning to support their cancer free state), but we do not have any long term "surgery only" cases. I am very much interested in this subject as I am an adept of the quality surgery done first but if by any unfortunate chance there will be a growth in Ivan's lung nodules then we will have to decide again reg. 2 courses of chemo before of the next resection (providing they will be resectable). Doing VATS for the centrally located mets is not a good idea as most probably it will not be less traumatic then the open thoracotomy and th probability is very high that the procedure will be converted to the open thoracotomy during the surgery (with intubation and epidural done as an emergency procedure which is not that good). It is a good technique to use the ultrasound to detect the smaller nodules but he can use it at the open surgery too. But how is he going to resect the centrally located ones having no laser tool?

Hi Olga, Based on what I've heard about combined VATS-U/S, the lung is deflated which actually allows more access to certain regions such as the lung bases and apices. I do not know specifically about mediastinal access, although I think I read that this technique is also successfully used for resection of mediastinal tumors. Gow is a pediatric thoracic surgeon (ie not an interventional radiologist), so I imagine if he thinks open thoracotomy is better he will do that instead. We haven't seen him yet and he has to look at her films.

This is more info from the poster: "The case records of 19 consecutive patients presenting with alveolar soft part sarcoma aged 15 years and over between 1984 and 2000 were reviewed retrospectively. Data were evaluated with respect to patient characteristics, location of primary tumour, frequency and site of metastases, recurrence, treatment outcome and death. Survival was defined as the interval between diagnosis and death or last follow-up visit. PFS was defined as the time from diagnosis to relapse, death, disease progression, or most recent follow up visit. The last follow up visit in the group was November 16, 2000 and the median follow up duration of surviving patients is 68.1 months (range, 21.8 – 222.6)." So the median follow up was 6 years with the longest 18 years.

I agree the wording is confusing, but I guess I inferred especially as the conclusion was that "pulmonary metastases may be curative and should be pursued aggressively even if repeated metastasectomies are required", the surgical cures were in the absence of chemo, or at least CR only occurred after definitive surgery. I bet many cases are difficult to evaluate because with progressive disease, chemo may be more likely to be added onto surgery.

Based on the Judson info, I would think if tumors regrow after awhile, repeat surgery would be what he would opt for. In the unusual event of very rapid regrowth of tumors (? Tammy), chemo might especially be effective though because the agents are usually more effective for rapidly dividing cells.

Hey all

This is the part of the forum that we all like to have as our focal point..especially this time of year as the holiday stress comes upon us.
I like what Dr F and Olga started in trying to lay out succes stories to help us all focus on something good in our lives.
Ivan brought up an intersesting subject of the possiblity of growth after surgeries as scar tissue starts to heal.
Josh , my son . also brought up some reservations that the cyro doctor, Dr Litthrup , had the possiblities of causing some growth as a result of cyro.
I've performed some research and came up with this link
Click here: Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors
This may not be exactly what we were talking about and Olga you can remove this if it doesn't fit the bill

My reason for posting here is that maybe with the right sequence we can keep this monster at bay and possible develope a cure
Surgery certainly needs to happen regardless. I am NOT discouraging surgery. However this may give more info for the surgeons and onocologist to help us in this fight.

As always I join everyone in saying, let there be a cure discovered

Much love
Debbie

Hey All
I love that Dr F. and Olga have this available to us as our rock
I love this part of the forum to read and use as my focal point

Ivan discussed his treatement of surgery and he ran by some food for thought on what I understood to be that surgery and secondary growth CAN go hand in hand
It all started with doctor Litthrups suggesting to my son that he might want to reconsider a Cyro treatment to some new tumors that popped up on a scan after laser surgery
The reason being possible exasherbating the growth either in that lung or in that area?

The links I came across were :

http://www.ncbi.nlm.nih.gov/pubmed/2189944

http://www.pnas.org/content/109/38/15101.long

My thought for putting a post here was to possible add to the documentation of treatments that could prolong and cure lives. With these understandings that we have in front of us the better we can fight this disease with surgery, chemo andTKIs

The more information we have to give to the professionals the better chance we have for a cure

Much Love
Debbie

The posts that Olga and Fer made together were amazing!
Two brilliant love driven woman!

Maybe one day the team will re connect again... But, until then we have these posts and we have Olga