Hello all. I've posted under other topics (like anti-angiogenesis), but this seemed like the best place to summarize our daughter's experiences. We just returned from UCLA and are thankful to report complete resection of her primary with negative margins (yippee!)! Surgeons were Dr. Fritz Eilber and Shlomo Raz and they were awesome. Wonderful teams at UCLA, including pain service. She had virtually no pain immediately post-op, though some aches and stiffness after switched to orals and began to move more. She was discharged on the 4th day.
Our brief summary: 'K' was 10 years old when she notice a lump in her female area. Thought to be a Bartholin cyst, attempt to drain, but discovered ASPS by core needle biopsy.
To Dana Farber: Saw John Goldberg (peds onc) and Chris Weldon (surgeon). Weldon recommended hemipelvectomy and mentioned possible removal of all pelvic organs, colostomy, urostomy, cystostomy. We learned several hemipelvectomies had been performed for pelvic sarcomas at DF recently. Weldon also talked about the need to embolize the tumor pre-operatively because of its vascular nature, and we were worried that that would increase the likelihood of metastases. My husband and I looked at scans (we are docs, but not oncologists, thought hemipelvectomy didn't make sense) - sought second opinion, found NIH surgeon who wrote a book on pelvic sarcomas, he recommended Dr Fritz Eilber at UCLA.
Sutent trial: While arranging for a second opinion and not wanting to launch immediately to hemipelvectomy, we talked to Dr Goldberg and our local oncologist in Seattle Dr Doug Hawkins, and decided to try Sutent to see if it could shrink the primary, simplifying surgery. Sutent went very well, 'K' could still attend school and still made A/B honor roll. She completed 4 courses of Sutent in all. We managed to get Premera to pay for it all.
To UCLA: Wonderful sarcoma group at UCLA. On 1/25/08, 'K' had her pelvic ASPS removed with negative margins. Total surgery time just 2 hrs. Fritz coordinated his surgery with Dr Shlomo Raz ("guru of pelvic reconstructive surgery" and a very nice guy) and 'K' had included a pretty remarkable reconstruction that made everything look normal. She had minimal blood loss, no transfusion needed. Also was able to arrange kinase typing of tumor at Clarient and Sloan Kettering (met), and donation of primary to Vistica at NCI and UCLA.
Before surgery, MRI on Sutent had suggested a partial response but no change in size. Over the 6 months on Sutent, it looked as if the pelvic primary did not grow, but 2 of 3 lung nodules did, and new 1 mm lung nodules appeared.
Path of primary showed minimal necrosis in response to Sutent (5%), but Dr Fritz told us that targeted agents can look like this - he had taken out GISTs on Nexavar that had been stable for several years - little necrosis, but tumor cells had stopped growing. Nevertheless, this was the end of the line for Sutent for us now because of the growth of lung nodules - there is also some feeling that larger lesions are more responsive to Sutent than new small ones. Also it made us wary of MRI responses to therapy for ASPS.
We have been in touch with Dr Goldberg still, but recently learned he moving to Miami and at DF, at least in peds onc, they did not recommend removal of lung mets. Isn't that surprising? There is considerable variation re: recommended treatment at major sarcoma centers.
UCLA, Seattle (and other places like MDA, MSK) do recommend removal of lung mets, and so we are proceeding with this. We are also considering the option of short course of neoadjuvant therapy before nodules are removed. That way we could have some idea that systemic therapy would work, if we have no visible disease to follow. I'll keep you posted about this. We may see whether we can get access to some investigation drugs.
Our path results so far:
Clarient:
c-myc FISH NOT amplified
topo-isomerase II-alpha NOT amplified
thymidylate synthase (TS) Negative
COX2 POSITIVE (100% cells, 1-2 intensity)
PTEN NO loss of expression
Tau POSITIVE (2+)
VEGF POSITIVE (90% cells, 2-3+ intensity)
ERCC1 HIGH (100% cells, 3 intensity)
GST pi Low (0% cells, 0 intensity)
PDFR Alpa Negative
PDFR Beta POSITIVE (100% cells, 2 intensity)
UCLA:
NEGATIVE ER, PR, HER-2, CD20, c-kit, EGFR
We are waiting for all the data before we pow-wow with our doctors and decide what we want to do next. We found the cancer typing helpful so far in deciding possible adjuvant therapies.
'K' from USA - Dx 2007 at 10 years old
Congrats on a good surgery outcome!
Dear 'F', thank you very much for updating us and sharing all of the valuable information on the rare experience of the ASPS abdominal surgery. It is very important observation that the opinion about resectability can be so different between surgeons based on their personal experience. It is well known that ASPS rarely recurs locally even if negative margins are minimal or border-like. So this is very unacceptable approach for the surgeon to offer such a mutilating surgery to a child with ASPS as it is generally a slow growing sarcoma and it case it recurs there is usually a second (third...) chance to do a second surgery and revise the tactics. I have to admit that in other sarcomas (especially bone sarcomas in pelvic locations) there are cases when very comprehensive resection is the only chance of survival but it doesn't mean that it is reasonable to apply this approach to the slow growing soft tissue sarcomas.
I am also very glad that in all of the hassle of the surgery you found a heart to do a molecular profile (and I suggest you to post the results into the related topic that we have) and especially that you donated the tumor tissue to D.Vistica, he is a very dedicated scientist that we are happy to have on our team and we have to help him to have as much tissue as possible to conduct this very important ASPS research.
I wish all of the best to 'K' and I urge you not to be very supportive of her moving to much and to fast, she has to be very cautious not to damage any of the inside stitches. We have learned in a very hard way that you need to restrict the child for awhile after the surgery to protect the wound from accidental damage.
I am also very glad that in all of the hassle of the surgery you found a heart to do a molecular profile (and I suggest you to post the results into the related topic that we have) and especially that you donated the tumor tissue to D.Vistica, he is a very dedicated scientist that we are happy to have on our team and we have to help him to have as much tissue as possible to conduct this very important ASPS research.
I wish all of the best to 'K' and I urge you not to be very supportive of her moving to much and to fast, she has to be very cautious not to damage any of the inside stitches. We have learned in a very hard way that you need to restrict the child for awhile after the surgery to protect the wound from accidental damage.
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Fictional
I just wanted to update you with 'K''s progress. When I get a chance, I'll post more results from the molecular profiling we did on two of 'K''s lung nodules.
Similar to some other folks here, I think, 3 months after resection of 'K''s primary, it looked as if there was more aggressive growth of some of 'K''s lung nodules and the appearance of some others. We (and our team at UCLA) wonder if this is an expected "aggressive" phase of ASPS...after the primary is resected, microscopic spread may go to the lungs, and one may see the fastest growing nodules first.
We became concerned when we saw that her Chest CT in late March showed rapid growth of a single lung nodule that now encroached on her heart, major vessels, and main bronchus.
As a result, we somewhat hastily drove down to UCLA to see her CT surgeon Jay Lee, and she underwent a thoracotomy 4/1. Lee saw 7 nodules on the left by spiral CT, but found 11 total intraoperatively. While most of the others were small, the rapidly growing nodule was close to the hilum and he said that if the nodule were to double again, then it could have meant having to have a complete pneumonectomy to clear her of all gross disease.
Thankfully, 'K' did remarkably well, although is still sleepy and gets sore in-between her current pain meds. We were grateful that 'K' was able to be discharged on postop day 3 and we just got back home. Prior to the surgery, she had repeat staging of everything - head MRI, CT abdomen & pelvis, but (praise God) we only found tumor in her lungs. By CT it looked like 7 on the left and 3 or 4 on the right.
We typed 2 nodules - the rapidly growing one at the hilum and one "representative" small one. The most important info for us was that whereas the primary was 100% COX2-positive (suggesting Celebrex might be beneficial), neither lung nodule was COX2 positive. Ki67 staining appeared to correlate with the differences in growth we saw in her different tumors (primary, fast lung nodule, slow nodule; 26%, 40%, 5%) - this is a marker of proliferation. We also found that the 3 tumors differed in VEGF IHC - primary was 90% positive, fast growing nodule was 70% VEGF, and the small nodule was VEGF and PDGF negative. This might explain why it seemed we saw a halt of growth with Sutent in 'K''s primary, but not her small lung nodules.
This is "clonal variation" - and why ASPS may be so frustrating to treat. Because different mets are molecularly different, medication may treat some nodules, but then others may be unaffected and continue to grow (and have to be surgically removed or ablated).
We are waiting for met IHC on the lung nodule. We are told that 'K' may still be completely resectable from the gross disease point of view, but because the others (on the right lung) are very small, we have a few months time to test an adjuvant drug. We had sought XL880 from Exelixis, and apparently got permission from the company, GlaxoSK, and FDA, but John Goldberg left DF (headed to Miami) and the peds onc who inherited the sarcoma clinic (Albritton) was apparently reluctant to recommend 'K' for the adult trial because she felt ASPS is an "indolent disease". Our Seattle doc was trying to see if she would change her mind if she saw 'K''s latest worsening Chest CT (prior to surgery).
Nevertheless, we are also looking into ARQ197 at their site in Santa Monica. The PI there turns out to be someone I knew from junior high (Lee Rosen). He told me he has 10 ASPS patients on ARQ197. All have tolerated the medication well, and it looks as if there is some antitumor activity with it. It seemed that his best responder had 30% reduction in tumor size (I am thinking RECIST), although many had some tumors shrink while others continue to grow (perhaps the clonal variation problem).
We are trying to obtain an age waiver and don't know whether we can get through their IRB, though they seem optimistic. Our tentative plan would be to have 'K' start ARQ197 for a limited course (few months). If the nodules shrank, we would continue of course, but if they grew, we would probably surgically remove them and examine the nodules for treatment effect. The idea would be that we could learn whether the medication were effective for her tumors this way.
We may also research into the possibility of RFA for 1 of the nodules in 'K''s right lung, though. This is only 5 mm, but if it were to get much larger, we would worry about the hilum / vessels / bronchus thing again. Because the nodule is deep, it is probably not easily taken out by a wedge, and we want to conserve as much lung as possible.
Similar to some other folks here, I think, 3 months after resection of 'K''s primary, it looked as if there was more aggressive growth of some of 'K''s lung nodules and the appearance of some others. We (and our team at UCLA) wonder if this is an expected "aggressive" phase of ASPS...after the primary is resected, microscopic spread may go to the lungs, and one may see the fastest growing nodules first.
We became concerned when we saw that her Chest CT in late March showed rapid growth of a single lung nodule that now encroached on her heart, major vessels, and main bronchus.
As a result, we somewhat hastily drove down to UCLA to see her CT surgeon Jay Lee, and she underwent a thoracotomy 4/1. Lee saw 7 nodules on the left by spiral CT, but found 11 total intraoperatively. While most of the others were small, the rapidly growing nodule was close to the hilum and he said that if the nodule were to double again, then it could have meant having to have a complete pneumonectomy to clear her of all gross disease.
Thankfully, 'K' did remarkably well, although is still sleepy and gets sore in-between her current pain meds. We were grateful that 'K' was able to be discharged on postop day 3 and we just got back home. Prior to the surgery, she had repeat staging of everything - head MRI, CT abdomen & pelvis, but (praise God) we only found tumor in her lungs. By CT it looked like 7 on the left and 3 or 4 on the right.
We typed 2 nodules - the rapidly growing one at the hilum and one "representative" small one. The most important info for us was that whereas the primary was 100% COX2-positive (suggesting Celebrex might be beneficial), neither lung nodule was COX2 positive. Ki67 staining appeared to correlate with the differences in growth we saw in her different tumors (primary, fast lung nodule, slow nodule; 26%, 40%, 5%) - this is a marker of proliferation. We also found that the 3 tumors differed in VEGF IHC - primary was 90% positive, fast growing nodule was 70% VEGF, and the small nodule was VEGF and PDGF negative. This might explain why it seemed we saw a halt of growth with Sutent in 'K''s primary, but not her small lung nodules.
This is "clonal variation" - and why ASPS may be so frustrating to treat. Because different mets are molecularly different, medication may treat some nodules, but then others may be unaffected and continue to grow (and have to be surgically removed or ablated).
We are waiting for met IHC on the lung nodule. We are told that 'K' may still be completely resectable from the gross disease point of view, but because the others (on the right lung) are very small, we have a few months time to test an adjuvant drug. We had sought XL880 from Exelixis, and apparently got permission from the company, GlaxoSK, and FDA, but John Goldberg left DF (headed to Miami) and the peds onc who inherited the sarcoma clinic (Albritton) was apparently reluctant to recommend 'K' for the adult trial because she felt ASPS is an "indolent disease". Our Seattle doc was trying to see if she would change her mind if she saw 'K''s latest worsening Chest CT (prior to surgery).
Nevertheless, we are also looking into ARQ197 at their site in Santa Monica. The PI there turns out to be someone I knew from junior high (Lee Rosen). He told me he has 10 ASPS patients on ARQ197. All have tolerated the medication well, and it looks as if there is some antitumor activity with it. It seemed that his best responder had 30% reduction in tumor size (I am thinking RECIST), although many had some tumors shrink while others continue to grow (perhaps the clonal variation problem).
We are trying to obtain an age waiver and don't know whether we can get through their IRB, though they seem optimistic. Our tentative plan would be to have 'K' start ARQ197 for a limited course (few months). If the nodules shrank, we would continue of course, but if they grew, we would probably surgically remove them and examine the nodules for treatment effect. The idea would be that we could learn whether the medication were effective for her tumors this way.
We may also research into the possibility of RFA for 1 of the nodules in 'K''s right lung, though. This is only 5 mm, but if it were to get much larger, we would worry about the hilum / vessels / bronchus thing again. Because the nodule is deep, it is probably not easily taken out by a wedge, and we want to conserve as much lung as possible.
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Bonni Hess
- Senior Member
- Posts: 1678
- Joined: Mon Aug 14, 2006 11:32 pm
- Location: Sammamish, WA USA
Dear 'F',
As always, I am so deeply appreciative of your faithful and very informative updates. I am so very sorry to hear that precious 'K' has had to endure another surgical procedure, but am extremely grateful that her rapidly growing lung met was able to be safely and successfully resected before it was able to grow any larger and impact her hilum, heart, vessels, or bronchus. I am also very glad and greatly relieved to hear that her brain/head, abdominal, and pelvic scans showed no new tumors. Your experience certainly exemplifies the critical importance of vigilant routine scanning and treatment of mets, and being very proactive and as informed and knowledgeable as possible. It is very interesting to hear that there are currently ten ASPS patients being treated with ARQ197 in California, and we will of course all be very interested in the results of their treatment. I just wish that more ASPS patients would actively participate and communicate on this Web site to share vitally important treatment information as you so graciously do. I continue to firmly believe that anecdotal and researched information sharing are one of our greatest weapons in trying to fight this extremely challenging and poorly understood disease. If you decide to go forward with RFA to try to destroy 'K''s remaining CT visible lung mets, I would be glad to provide you with any information that I can based on our recent experience and seemingly/Hopefully successful outcome with Brittany's lung RFA at the University of Pittsburgh. In the meantime, please take care 'F', give dear little 'K' a gentle hug, and keep this Web site updated as you are able.
With special caring thoughts and continued Hope,
Bonni
As always, I am so deeply appreciative of your faithful and very informative updates. I am so very sorry to hear that precious 'K' has had to endure another surgical procedure, but am extremely grateful that her rapidly growing lung met was able to be safely and successfully resected before it was able to grow any larger and impact her hilum, heart, vessels, or bronchus. I am also very glad and greatly relieved to hear that her brain/head, abdominal, and pelvic scans showed no new tumors. Your experience certainly exemplifies the critical importance of vigilant routine scanning and treatment of mets, and being very proactive and as informed and knowledgeable as possible. It is very interesting to hear that there are currently ten ASPS patients being treated with ARQ197 in California, and we will of course all be very interested in the results of their treatment. I just wish that more ASPS patients would actively participate and communicate on this Web site to share vitally important treatment information as you so graciously do. I continue to firmly believe that anecdotal and researched information sharing are one of our greatest weapons in trying to fight this extremely challenging and poorly understood disease. If you decide to go forward with RFA to try to destroy 'K''s remaining CT visible lung mets, I would be glad to provide you with any information that I can based on our recent experience and seemingly/Hopefully successful outcome with Brittany's lung RFA at the University of Pittsburgh. In the meantime, please take care 'F', give dear little 'K' a gentle hug, and keep this Web site updated as you are able.
With special caring thoughts and continued Hope,
Bonni
'K''s lung surgery
'F', hi, I just have a time to comment on your message reg. 'K''s lung surgery and second lung situation and RFA option.
I am very glad to hear that surgery went well. I hope that her pain is well controlled, we should share more info about it in some topic here on the board.
I would not advise you to have an RFA of it before of the subsequent surgery as the track of the RFA needle forms an adhesion that needs to be cut when the lung is open for the surgery and it is more bleeding and complicates the surgery and gives you very little benefit. I advocate that the first lung treatment would be open surgery with the rest of the options reserved for the recurrences, then the surgery option will be used its best and more small mets will be found with the surgeon acting under the optimal conditions. Also I have seen an article that earlier surgery to remove lung mets is beneficial for the patient instead or doing it later in course of the disease (to do it sooner when they found instead of waiting and doing the surgery when mets are symptomatic).
I also extremely impressed with the thorough research that is done for her lung mets and I am asking you to copy the message into the Molecular studies topic to collect this info there, I hope that we get some doctor reading it and you might want to send an e-mail to Drs.Dina Lev and David Vistica - they might be interested to get an additional info to store it into the mounting pile of the information about ASPS angiogenesis profile. I suspected a long time ago that small ASPS metastases and the bigger ones are different, and I still think that the smaller ones - 1-3 mm might be chemoresponsive. Also Dr.Rolle said to me that they find that mets less then 2 mm have no blood supply, they have angiogenesis independent growth for a while.
I am very glad to hear that surgery went well. I hope that her pain is well controlled, we should share more info about it in some topic here on the board.
I would not advise you to have an RFA of it before of the subsequent surgery as the track of the RFA needle forms an adhesion that needs to be cut when the lung is open for the surgery and it is more bleeding and complicates the surgery and gives you very little benefit. I advocate that the first lung treatment would be open surgery with the rest of the options reserved for the recurrences, then the surgery option will be used its best and more small mets will be found with the surgeon acting under the optimal conditions. Also I have seen an article that earlier surgery to remove lung mets is beneficial for the patient instead or doing it later in course of the disease (to do it sooner when they found instead of waiting and doing the surgery when mets are symptomatic).
I also extremely impressed with the thorough research that is done for her lung mets and I am asking you to copy the message into the Molecular studies topic to collect this info there, I hope that we get some doctor reading it and you might want to send an e-mail to Drs.Dina Lev and David Vistica - they might be interested to get an additional info to store it into the mounting pile of the information about ASPS angiogenesis profile. I suspected a long time ago that small ASPS metastases and the bigger ones are different, and I still think that the smaller ones - 1-3 mm might be chemoresponsive. Also Dr.Rolle said to me that they find that mets less then 2 mm have no blood supply, they have angiogenesis independent growth for a while.
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Fictional
Will do, Olga. Thanks for your comments about RFA.
We also got quite a surprise yesterday when we heard that the lung nodule we sent to Ladanyi was found to be met-negative for IHC. There are caveats of course - this nodule was the most rapidly growing and highest Ki67...so it may have undergone a genetic mutation to accelerate its proliferative rate, so no dependent on the expression of met. Also Ladanyi said be careful about concluding too much from this - as his IHC staining is not established to be a predictor of who should try a met inhibitor (we understand this, with immunohistochemistry, there are individual antibody questions / epitopes, etc). Still it was quite a surprise. Also this is only 1 nodule out of many. Maybe this is why surgery is better than chemo (physically remove the worse and fastest growing clones)!
This does make us at least pause to question whether it would be worthwhile to enter the ARQ197 trial. We have put the question out to our docs and are hearing back. We have also started 'K' on Celebrex. Both 'K''s lung nodules tested were negative for COX2 (but primary positive), but we know there is naturally occurring COX2 in the lung, and there is evidence that COX2 can both decrease VEGF and downregulate met pathways. It also has antitumor effect in many vascular cancers.
We still haven't heard about IRB approval for ARQ197, but we did find out that they did not find Celebrex to be a contraindication (so she can potentially be on it and ARQ197 if we go that route).
If it may help decision making of physicians or scientists, we are of course willing to forward copies of 'K''s pathological studies and molecular profiling. Anyone is welcome to contact us by email.
Finally, 'K' has recovered beautifully from her thoracotomy. She had total probably less than an hour of significant pain (in hospital when transitioning from epidural to pills and trying to find the right dose), although the chest tubes and a neck line (EJ) were uncomfortable while they were still in.
She did well with 5 mg oxycodone and was able to taper off completely from week 2-3 post surgery. As the oxycodone went off, the Celebrex came on, and 'K' found she was without pain. Sometimes when she takes a deep breath to yawn she finds it aches. 'K''s been back to school since week 2 post-surgery, though she's been told to wait on PE until after 4-5 weeks post.
We also got quite a surprise yesterday when we heard that the lung nodule we sent to Ladanyi was found to be met-negative for IHC. There are caveats of course - this nodule was the most rapidly growing and highest Ki67...so it may have undergone a genetic mutation to accelerate its proliferative rate, so no dependent on the expression of met. Also Ladanyi said be careful about concluding too much from this - as his IHC staining is not established to be a predictor of who should try a met inhibitor (we understand this, with immunohistochemistry, there are individual antibody questions / epitopes, etc). Still it was quite a surprise. Also this is only 1 nodule out of many. Maybe this is why surgery is better than chemo (physically remove the worse and fastest growing clones)!
This does make us at least pause to question whether it would be worthwhile to enter the ARQ197 trial. We have put the question out to our docs and are hearing back. We have also started 'K' on Celebrex. Both 'K''s lung nodules tested were negative for COX2 (but primary positive), but we know there is naturally occurring COX2 in the lung, and there is evidence that COX2 can both decrease VEGF and downregulate met pathways. It also has antitumor effect in many vascular cancers.
We still haven't heard about IRB approval for ARQ197, but we did find out that they did not find Celebrex to be a contraindication (so she can potentially be on it and ARQ197 if we go that route).
If it may help decision making of physicians or scientists, we are of course willing to forward copies of 'K''s pathological studies and molecular profiling. Anyone is welcome to contact us by email.
Finally, 'K' has recovered beautifully from her thoracotomy. She had total probably less than an hour of significant pain (in hospital when transitioning from epidural to pills and trying to find the right dose), although the chest tubes and a neck line (EJ) were uncomfortable while they were still in.
She did well with 5 mg oxycodone and was able to taper off completely from week 2-3 post surgery. As the oxycodone went off, the Celebrex came on, and 'K' found she was without pain. Sometimes when she takes a deep breath to yawn she finds it aches. 'K''s been back to school since week 2 post-surgery, though she's been told to wait on PE until after 4-5 weeks post.
Dear 'F', I have some anecdotal experience with Celebrex and my son -- he was on Celebrex 100 mg bid increasing up to 200 mg bid and low dose Interferon 5 miu 3 times weekly, approx. 5/2002-12/2003, then 4 times weekly until his first brain tumor presented 6/2004. During that period of time when he was on Celebrex and Interferon -- lung met progression was slow -- and when his doc stopped therapy with Interferon and Celebrex because the brain met presented, we saw afterwards the greatest rate of growth to the larger lung mets from his June to Sept. scans.
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Fictional
Thanks Beth, for sharing this. This is helpful to know.
The dose of Celebrex was / is tricky to pick. I saw that Amanda in this forum was on 400 BID (with Vinblastine) with resolution of her lung nodules after more than a year, but 400 BID has been associated with increased cardiovascular complications in other cancer trials. Our peds onc was really reluctant to have 'K' try this.
On the other hand, 100 BID seemed too low (based on colon CA trials) to have a significant antitumor effect, but in the end we are hoping 200 BID may have a beneficial effect without too much CV toxicity. 200 BID is undergoing clinical trial for kids and high risk for developing colon CA.
The dose of Celebrex was / is tricky to pick. I saw that Amanda in this forum was on 400 BID (with Vinblastine) with resolution of her lung nodules after more than a year, but 400 BID has been associated with increased cardiovascular complications in other cancer trials. Our peds onc was really reluctant to have 'K' try this.
On the other hand, 100 BID seemed too low (based on colon CA trials) to have a significant antitumor effect, but in the end we are hoping 200 BID may have a beneficial effect without too much CV toxicity. 200 BID is undergoing clinical trial for kids and high risk for developing colon CA.
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Fictional
We just heard 'K''s been accepted to ARQ197 study. We have decided to proceed with this. It is also OK with the study to continue on Celebrex, so our "neoadjuvant" trial will be Celebrex + ARQ 197. She will probably be able to start drug the week of May 12th. The study will require frequent visits to LA in the first 5 weeks, but we are trying to cobble together frequent flyer miles.
Our brief recap: 'K''s primary was 100% COX positive, 90% VEGF positive, 70% PDGF beta, and positive for cytoplasmic and transmembrane IHC Met. 'K' was on Sutent for 4 courses with growth arrest in the primary, but growth in some (but not all) lung mets and some new ones. 11 lung mets were resected. The largest one was 0% COX2 and 0%Met, 60% VEGF. A representative small one was 0% COX2, 0% VEGF, PDGF beta negative. For those interested in markers, GSTpi was high in the primary and large nodule, but low in the small nodule. Clonal variation may be the reason why surgery should always be considered for tumors unresponsive to medical treatment. We decided to go with Celebrex + ARQ197 for the possibility it may reduce the likelihood of future clones surviving and possibly reduce spread of metastases outside the lung. If it could help kill of the few lung nodules on the right, that would be great too, but we do not know of any complete responses.
We are happy to enter ARQ197 soon because it seemed to us that the time post-surgery is an active time for spread of microscopic disease, and subsequent metastases. 'K' is 11 years old, 2 years below their lowest posted age for the study, so we had to apply for an age waiver.
For patients on the study younger than 20 years old, unfortunately there's a requirement for more blood draws for pharmacokinetics, but I told 'K' that on the positive side we will know she is receiving the right dosing of drug. I will post our experiences with the study under the ARQ197 heading, and also what we have heard about ASPS' responses so far. They will pay for our hotel and PET studies.
Our tentative plan beyond this is to have what seem to be the last remaining visible tumors removed from her right lung after at least two courses of ARQ 197. The nodules are small (2-4 mm), but one deserves more watching because it is close to the hilum. The surgeon may be able to get them with VATS.
'K' has been back in school since 2 weeks post thoracotomy and feeling great. She caught up with all her schoolwork and even managed to help her team win in their mock trial at the capitol this past week.
Our brief recap: 'K''s primary was 100% COX positive, 90% VEGF positive, 70% PDGF beta, and positive for cytoplasmic and transmembrane IHC Met. 'K' was on Sutent for 4 courses with growth arrest in the primary, but growth in some (but not all) lung mets and some new ones. 11 lung mets were resected. The largest one was 0% COX2 and 0%Met, 60% VEGF. A representative small one was 0% COX2, 0% VEGF, PDGF beta negative. For those interested in markers, GSTpi was high in the primary and large nodule, but low in the small nodule. Clonal variation may be the reason why surgery should always be considered for tumors unresponsive to medical treatment. We decided to go with Celebrex + ARQ197 for the possibility it may reduce the likelihood of future clones surviving and possibly reduce spread of metastases outside the lung. If it could help kill of the few lung nodules on the right, that would be great too, but we do not know of any complete responses.
We are happy to enter ARQ197 soon because it seemed to us that the time post-surgery is an active time for spread of microscopic disease, and subsequent metastases. 'K' is 11 years old, 2 years below their lowest posted age for the study, so we had to apply for an age waiver.
For patients on the study younger than 20 years old, unfortunately there's a requirement for more blood draws for pharmacokinetics, but I told 'K' that on the positive side we will know she is receiving the right dosing of drug. I will post our experiences with the study under the ARQ197 heading, and also what we have heard about ASPS' responses so far. They will pay for our hotel and PET studies.
Our tentative plan beyond this is to have what seem to be the last remaining visible tumors removed from her right lung after at least two courses of ARQ 197. The nodules are small (2-4 mm), but one deserves more watching because it is close to the hilum. The surgeon may be able to get them with VATS.
'K' has been back in school since 2 weeks post thoracotomy and feeling great. She caught up with all her schoolwork and even managed to help her team win in their mock trial at the capitol this past week.
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Fictional
Re: 'K'
Our update - 'K' was continuing to feel well on ARQ197 and High dose Celebrex. She finished 13 weeks of ARQ197 and longer of Celebrex, but it was only increased from low dose Celebrex (200 BID) to high dose (400 BID) 5 weeks ago.
Our July scans for the first time showed no new lung nodules, but we were disappointed to see growth in probably most lung nodules. At least by my eye, it seemed as more rapid growth was seen on the R (unoperated side). Still, it is possible this drug combo is working a little - the growth was much slower than we had seen between 12/07-3/08..but that might have been a rebound effect from going off Sutent and having the primary removed.
After the July scans, ARQule said we could continue on the meds, but we were hoping to do a R thoracotomy back at UCLA. This changed when we met with Jay Lee. He seemed in no hurry to do the operation on the right, but didn't give us clear-cut reasons - though we knew the presence of a deep nodule on the right might require lobectomy if an attempt were made to clear all lung lesions.
So we went back home and decided to check back in with the first lung surgeon (actually a general surgeon) we had seen at Seattle Childrens. Ken Gow had planned bilateral thoracotomies soon after her diagnosis, but we went with UCLA (a CT surgeon) when it was apparent there was a rapidly growing nodule near her heart.
Now we wanted Gow's opinion on clearing the right lung - to our surprise, he said sadly he felt she was no longer operable. He told us her L surgery took out quite a lot of lung, and although there were not many, there were 2 deep nodules on the R, 2 deep nodules on the L - and the only way to remove these would be to remove lobe bilaterally, but that would take out too much lung. It was very hard to hear this, but we took a long hard look at her scans and we saw how much lung was removed with 'K''s L thoracotomy, and we understood if you removed as much to remove the deep nodules, it would be severely debilitating.
We sent 'K''s films out to David Schrump at NCI, Axel Rolle in Germany, and made an appointment with Rob MCKenna at Cedars Sinai (LA), and began digging through the literature again. To our surprise the first responder was Axel Rolle who agreed to take 'K' for R thoracotomy if you can "come to Germany this weekend." He said he has too many commitments in September, but if we could come quickly, he would clear her R, and depending on how that goes, think about clearing her L a few months later.
To make a long story short, we decided to do laser ablation for 'K' this coming week with Rolle. We are hoping ARqule will let us resume ARQ197 after this surgery, but we're not sure they well (Lee Rosen is asking). This was a difficult decision, but looking at her scans her worst nodules are on the R (2 deep are near the pulmonary artery...a few more doubling times and we feared they could become unresectable). Our net decision was how much more normal lung could be spared with the laser technique.
So we are in a mad rush to get everything done (we have a hotel in Coswig, hurrah! and I loaded a free talking German phrasebook on my Iphone). I am hoping Schrump would still look at her films (he had said he would be happy to look at them). Rolle said 'K' is a candidate for redo on the L (to clear of all visible disease), but we will have to see how things go.
Olga has been very helpful (thank you thank you thank you) as usual. Apparently 90% patients are refused by Rolle because of advanced disease, so we felt the pull to take Rolle up on his offer quickly. Fortunately we had passports.
How often in ASPS it happens that the docs say, just wait, just wait, and then the lungs become inoperable? Did Jay intend to operate eventually on the right - maybe.
We prayed about it and we hope we are making a good decision. I'll let you know how things are when we're back.
Our July scans for the first time showed no new lung nodules, but we were disappointed to see growth in probably most lung nodules. At least by my eye, it seemed as more rapid growth was seen on the R (unoperated side). Still, it is possible this drug combo is working a little - the growth was much slower than we had seen between 12/07-3/08..but that might have been a rebound effect from going off Sutent and having the primary removed.
After the July scans, ARQule said we could continue on the meds, but we were hoping to do a R thoracotomy back at UCLA. This changed when we met with Jay Lee. He seemed in no hurry to do the operation on the right, but didn't give us clear-cut reasons - though we knew the presence of a deep nodule on the right might require lobectomy if an attempt were made to clear all lung lesions.
So we went back home and decided to check back in with the first lung surgeon (actually a general surgeon) we had seen at Seattle Childrens. Ken Gow had planned bilateral thoracotomies soon after her diagnosis, but we went with UCLA (a CT surgeon) when it was apparent there was a rapidly growing nodule near her heart.
Now we wanted Gow's opinion on clearing the right lung - to our surprise, he said sadly he felt she was no longer operable. He told us her L surgery took out quite a lot of lung, and although there were not many, there were 2 deep nodules on the R, 2 deep nodules on the L - and the only way to remove these would be to remove lobe bilaterally, but that would take out too much lung. It was very hard to hear this, but we took a long hard look at her scans and we saw how much lung was removed with 'K''s L thoracotomy, and we understood if you removed as much to remove the deep nodules, it would be severely debilitating.
We sent 'K''s films out to David Schrump at NCI, Axel Rolle in Germany, and made an appointment with Rob MCKenna at Cedars Sinai (LA), and began digging through the literature again. To our surprise the first responder was Axel Rolle who agreed to take 'K' for R thoracotomy if you can "come to Germany this weekend." He said he has too many commitments in September, but if we could come quickly, he would clear her R, and depending on how that goes, think about clearing her L a few months later.
To make a long story short, we decided to do laser ablation for 'K' this coming week with Rolle. We are hoping ARqule will let us resume ARQ197 after this surgery, but we're not sure they well (Lee Rosen is asking). This was a difficult decision, but looking at her scans her worst nodules are on the R (2 deep are near the pulmonary artery...a few more doubling times and we feared they could become unresectable). Our net decision was how much more normal lung could be spared with the laser technique.
So we are in a mad rush to get everything done (we have a hotel in Coswig, hurrah! and I loaded a free talking German phrasebook on my Iphone). I am hoping Schrump would still look at her films (he had said he would be happy to look at them). Rolle said 'K' is a candidate for redo on the L (to clear of all visible disease), but we will have to see how things go.
Olga has been very helpful (thank you thank you thank you) as usual. Apparently 90% patients are refused by Rolle because of advanced disease, so we felt the pull to take Rolle up on his offer quickly. Fortunately we had passports.
How often in ASPS it happens that the docs say, just wait, just wait, and then the lungs become inoperable? Did Jay intend to operate eventually on the right - maybe.
We prayed about it and we hope we are making a good decision. I'll let you know how things are when we're back.
Re: 'K'
Hi 'F',
Thank you so much for your update on 'K'. I am sure things have been very busy around your house with this new change in plans. I just wanted to let you know that I am praying for you and your family. Praying that 'K' will respond wonderfully to his new treatment.
Please keep us posted on how she is doing and please know that you are being supported and prayed for.
Karen Imm
Thank you so much for your update on 'K'. I am sure things have been very busy around your house with this new change in plans. I just wanted to let you know that I am praying for you and your family. Praying that 'K' will respond wonderfully to his new treatment.
Please keep us posted on how she is doing and please know that you are being supported and prayed for.
Karen Imm
-
Fictional
Re: 'K'
Thanks for the prayers, Karen! We really appreciate them.
We had a little longer stay than anticipated because Dr. Rolle discovered a PFT abnormality on 'K''s stress PFTs and it turned out she has exercise-induced asthma (this runs in the family, but hadn't been suspected). It was nice to learn, but did add a week to our plans (high dose prednisone before surgery, now on taper). At least they let us sneak out on the weekend and tour downtown Dresden.
'K' had an uncomplicated surgery and thankfully should be returning next Monday. The first two days were still lousy, but thankfully that is all past.
We were impressed by Rolle and his team, and it was a pleasant surprise finding out how nice an area Coswig is and how beautiful Dresden is. There were 17 nodules by fine cut chest CT, Rolle removed 32, and we heard on path that 28 had cancer, 4 showed fibrosis. He thinks it was a complete resection. Hard to know what the fibrosis is, whether it's unrelated benign stuff or evidence of partial treatment effect. We will be asking for the formal report and also hope to get a paraffin block...this may be helpful for some of you who have seen Rolle who want to do some molecular profiling or kinase typing. Apparently usually the nodules are resected and not just burned, so the pathology can be checked and the tissue obtained for additional studies. The tissue has to be transferred to another lab though rather than given to patients directly, so we are going to have to get the paperwork to transfer it to our lab of choice (maybe UCLA since we know the pathologist well there).
Everyone was wonderful there (they let us be present in the OR when she was extubated!) and we were impressed by the physiotherapists...much better than the US. The US is better in other things though (like the timing of drug dosing etc). It was definitely handy to have Brock able to speak a little German. Because this is East Germany, younger people know more English than the older (forced to learn Russian).
With the additional tweaks for 'K''s asthma, she ended up have a larger vital capacity postop than preop for her initial lung surgery!
We would like to proceed with the left (redo) after 'K' recovers, but Rolle said with this sarcoma he has seen stabilization when one lung has been completely resected (? like Andreas ?) possibly due to immune competence and a reduction in tumor burden, so we will check a CT in 2 months and find out whether we return to Germany sooner or later.
Another thing we figured out with all this is that with conventional surgery surgeons have to choose to take only nodules they know for sure are cancer because so much normal lung needs to be removed (e.g. a segment) that way. On the other hand, with the laser, Rolle can remove every bump he sees (his benign nodule rate is 20%), and so potentially increase the likelihood of clearing the lung...you can take out the ones even you're not sure about. Not surprisingly, when 'K''s left lung was operated on with the conventional route, the surgery found 0 benign (11 cancer). It would seem to be a risk:benefit issue.
We also liked the surgical approach Rolle used for this thoracotomy better...muscle sparing...no cutting muscles. 'K''s arm movement is much better already and it is much more cosmetic. We could see Rolle was a little saddened he had not been able to do her first operation.
Thank you to everyone for their encouragement and prayers,
'F'
We had a little longer stay than anticipated because Dr. Rolle discovered a PFT abnormality on 'K''s stress PFTs and it turned out she has exercise-induced asthma (this runs in the family, but hadn't been suspected). It was nice to learn, but did add a week to our plans (high dose prednisone before surgery, now on taper). At least they let us sneak out on the weekend and tour downtown Dresden.
'K' had an uncomplicated surgery and thankfully should be returning next Monday. The first two days were still lousy, but thankfully that is all past.
We were impressed by Rolle and his team, and it was a pleasant surprise finding out how nice an area Coswig is and how beautiful Dresden is. There were 17 nodules by fine cut chest CT, Rolle removed 32, and we heard on path that 28 had cancer, 4 showed fibrosis. He thinks it was a complete resection. Hard to know what the fibrosis is, whether it's unrelated benign stuff or evidence of partial treatment effect. We will be asking for the formal report and also hope to get a paraffin block...this may be helpful for some of you who have seen Rolle who want to do some molecular profiling or kinase typing. Apparently usually the nodules are resected and not just burned, so the pathology can be checked and the tissue obtained for additional studies. The tissue has to be transferred to another lab though rather than given to patients directly, so we are going to have to get the paperwork to transfer it to our lab of choice (maybe UCLA since we know the pathologist well there).
Everyone was wonderful there (they let us be present in the OR when she was extubated!) and we were impressed by the physiotherapists...much better than the US. The US is better in other things though (like the timing of drug dosing etc). It was definitely handy to have Brock able to speak a little German. Because this is East Germany, younger people know more English than the older (forced to learn Russian).
With the additional tweaks for 'K''s asthma, she ended up have a larger vital capacity postop than preop for her initial lung surgery!
We would like to proceed with the left (redo) after 'K' recovers, but Rolle said with this sarcoma he has seen stabilization when one lung has been completely resected (? like Andreas ?) possibly due to immune competence and a reduction in tumor burden, so we will check a CT in 2 months and find out whether we return to Germany sooner or later.
Another thing we figured out with all this is that with conventional surgery surgeons have to choose to take only nodules they know for sure are cancer because so much normal lung needs to be removed (e.g. a segment) that way. On the other hand, with the laser, Rolle can remove every bump he sees (his benign nodule rate is 20%), and so potentially increase the likelihood of clearing the lung...you can take out the ones even you're not sure about. Not surprisingly, when 'K''s left lung was operated on with the conventional route, the surgery found 0 benign (11 cancer). It would seem to be a risk:benefit issue.
We also liked the surgical approach Rolle used for this thoracotomy better...muscle sparing...no cutting muscles. 'K''s arm movement is much better already and it is much more cosmetic. We could see Rolle was a little saddened he had not been able to do her first operation.
Thank you to everyone for their encouragement and prayers,
'F'
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Bonni Hess
- Senior Member
- Posts: 1678
- Joined: Mon Aug 14, 2006 11:32 pm
- Location: Sammamish, WA USA
Re: 'K'
Dear 'F',
It is so very good to hear from you and to hear about the successful outcome of dear 'K''s surgery. We are so deeply grateful that everything went well and that Dr. Rolle thinks that he got a complete resection, and we truly share your great relief, happiness, and strenghened Hope. Thank you for your continued faithful sharing of 'K''s treatment experiences. The invaluable detailed information which you so graciously share is a wonderful example of the vital importance of this interactive Web site in providing anecdotal treatment information on promising new treatments to other ASPS patients and their families. Please give dear 'K' a gentle hug, travel safe on your return trip, and know that our continued most caring thoughts and best wishes are with 'K' and your family.
With special caring and continued Hope,
Bonni
It is so very good to hear from you and to hear about the successful outcome of dear 'K''s surgery. We are so deeply grateful that everything went well and that Dr. Rolle thinks that he got a complete resection, and we truly share your great relief, happiness, and strenghened Hope. Thank you for your continued faithful sharing of 'K''s treatment experiences. The invaluable detailed information which you so graciously share is a wonderful example of the vital importance of this interactive Web site in providing anecdotal treatment information on promising new treatments to other ASPS patients and their families. Please give dear 'K' a gentle hug, travel safe on your return trip, and know that our continued most caring thoughts and best wishes are with 'K' and your family.
With special caring and continued Hope,
Bonni
-
Fictional
Good News!!
Good news! I got a call from Brock today who spent 2 hours talking to Dr Rolle and I think the pathologist. They said that there was definite indication of treatment effect in the lung nodules resected from 'K'. Initially Rolle had said he wouldn't recommend any adjuvant, but this pathology result change everything. We will arrange to have the blocks (all if possible) transferred to a US lab for confirmation.
He said that all of the small ones were fibrotic, a good prognostic sign with a study he had done on other metastectomy patients and some (or most??) nodules showed some evidence of necrosis. This is a definite change from 'K''s prior thoracotomy which showed 0 necrosis after 4 courses of Sutent (the primary showed 5% necrosis only). ASPS usually does not have much necrosis.
He said this might also fit with the idea of ARQ197 being an antimetastatic factor early in the course of disease ...prevent new metastases more than shrink existing large ones.
Obviously this is not 100% tumor kill, but the way we see it, any tumor necrosis is good tumor necrosis. If it could even prevent one tumor from developing, we welcome it.
It also looks as if all of the remaining tumor on the left lung is resectable, so we are talking to Premiere Oncology (who will have to talk to Arqule) to see if we can continue being on the study. 'K' has been on ARQ197 120 mg BID x 13 weeks, High dose Celebrex 400 BID x 5 weeks (previously 200 BID x 14 weeks), and green tea supplement twice a day (capsule).
These medications are completely asymptomatic from our standpoint, although that dose of Celebrex can be associated with cardiotoxicity if taken longer than 6 months.
He said that all of the small ones were fibrotic, a good prognostic sign with a study he had done on other metastectomy patients and some (or most??) nodules showed some evidence of necrosis. This is a definite change from 'K''s prior thoracotomy which showed 0 necrosis after 4 courses of Sutent (the primary showed 5% necrosis only). ASPS usually does not have much necrosis.
He said this might also fit with the idea of ARQ197 being an antimetastatic factor early in the course of disease ...prevent new metastases more than shrink existing large ones.
Obviously this is not 100% tumor kill, but the way we see it, any tumor necrosis is good tumor necrosis. If it could even prevent one tumor from developing, we welcome it.
It also looks as if all of the remaining tumor on the left lung is resectable, so we are talking to Premiere Oncology (who will have to talk to Arqule) to see if we can continue being on the study. 'K' has been on ARQ197 120 mg BID x 13 weeks, High dose Celebrex 400 BID x 5 weeks (previously 200 BID x 14 weeks), and green tea supplement twice a day (capsule).
These medications are completely asymptomatic from our standpoint, although that dose of Celebrex can be associated with cardiotoxicity if taken longer than 6 months.
Re: 'K'
'F'! That is great news! I would like to consider Dr. Rolle for possible surgery on Anthony (my fiance). How did you send the film? Did you have your physican send it? What is the best way to contact him?
It seems like you had such a great experience. We have worked with Dr. Schrump with NIH and if he helped you reach out to him - we can contact him as well. Thank you so much for any advice that you have to offer!
It seems like you had such a great experience. We have worked with Dr. Schrump with NIH and if he helped you reach out to him - we can contact him as well. Thank you so much for any advice that you have to offer!