Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Hello team!

Thanks a lot to everyone who shares their stories and ideas on this forum. I want to share my story and ask for a piece of advice from the community.
My name is Daria, I was born in 1980 in Siberia region (middle of Russia). My ASPS come in my life in 2012 when I was pregnant with my second daughter, 32yo.

Complaints
Appearance of new metastases in liver.

Medical history
Year 2008 – pain in the region of the middle of lower left rib, magnetic resonance imaging (MRI) of the lumbar region w/o pathological findings. Pain disappeared after manual therapy.

Year 2010 – pain in the same location (the middle of lower left rib), X-ray radiography w/o pathological findings. Pain disappeared after manual therapy.

February 2012. Tongue tumor. On week 23 of second pregnancy, MRI revealed an asymmetric space-occupying lesion (64x47x37 mm) with clear uneven margins and heterogeneous structure. Also, peripheral convoluted vascular structures were observed. Biopsy showed that the neoplasia was formed by large round-shaped cells with abundant granular cytoplasm, polymorphic nucleus, which formed solid and alveolar structures. The origin of the tumor was likely to be not epithelial. Immunohistochemical analysis revealed positive expression of St00, 25% of cells were Ki67+. Expression of vimentin was weak. Expression of desmin and common cytokeratines was also detected (?). Diagnosis: Granular cell tumor (synonyms: Abrikossoff's tumor, Granular cell myoblastoma, Granular cell nerve sheath tumor, and Granular cell Schwannoma).

May 2012. On pregnancy-week 33, second MRI revealed an increase in tumor size (64x63x43 mm), more pronounced involvement of the upper right parts of the radix linguae, essential edema of the lower right part of the radix linguae with deformation of the right components of oropharynx.

June 2012 (pregnancy-week 36) the tumor was excised. Morphological and cytological analysis of the excised tissue proved the granular cell tumor, rounded by a pseudocapsule and the remnants of fibrous, fat and skeletal muscular tissues. No treatment was applied after excision. That time I thought that this is the end of story. Unfortunately not..

February 2014: Acute severe pain in the region of the middle of lower left rib. MRI of the thorax revealed space-occupying lesion (28x33x20 mm) in Th9 accompanied by compound pathologic fracture of the vertebral body and mixed spinal stenosis at this level. Biopsy was taken. Microscopic tumor sections from 2012 (tongue tumor) were re-analyzed. Combined revision resulted in new diagnosis – metastasized alveolar soft-tissue sarcoma of the tongue (ASPS). In the biopsy from Th9 among blood cells single small bone fragment was found. It contained excrescence of tumor cells with profound cellular atypia. No alveolar structures were seen, while similarly to the tongue tumor large cells with abundant granular cytoplasm and the nucleus on the periphery were revealed.
X-ray radiography of the lungs and ultrasound examination of the lymph nodes and abdominal organs were performed, with no pathology revealed.

April 2014. Corpectomy of Th9 with anterior stabilization (endoprotesis ObeliscPRO). Morphological investigation of the excised material proved metastasis of the established primary (alveolar soft-tissue sarcoma of the tongue).

May 2014, permanently increasing pain in the operation region. By CT in the lumen of the spinal canal, a soft tissue formation (17x14x32 mm) was revealed. It extended from the lower 1/3 of Th8 to the upper 1/3 of Th10, partly obtruding the lumen of the th9-10 foraminal canal and compressing the dural sac. This formation was accumulating contrast. The lumen of spinal canal was narrowed to 9 mm. In the lungs diffusely located through all lung fields round shaped solid formations were revealed (size ranged from 5 mm to 14 mm, the largest one in S8 of the right lung) mainly on the blood vessels. After that I start use: Votrient (Pazopanib) 800 mg p.o. and Zometa (zoledronic acid) 4 mg i.v. once in 28 days.

May 2014. Israel’s Tel Aviv Sourasky Medical Center (http://medtour.tasmc.org.il/s#!/en) confirm diagnosis for ASPS with ASPL-TFE3 fusion transcript detection.

August 2014. Operation was performed versus ASPS that was sitting in spine Th8-9. It was robotic radiosurgery system Cyberknife in Russian clinic (oncostop.su).

Feb 2015. Corrective surgery on spine Th8-9 was performed, as pain was too big and harmful. During the operation (laminectomy) some part of the bone was removed in order to free nerves.

May 2015. Amount of metastasis and its size had been increased. Medical chemical treatment had been changed on Sutent (Sunitinib) and Zometa (Zoledronix acid).

July - Oct 2015. Negative dynamic was found out in lung for two met (26 mm, 20 mm). The rest met and met amount wasn’t changes.

Dec 2015. Operation was performed versus two met in lung by Cyberknife in Russian clinic (oncostop.su).

2015-2017 Every three month CT analysis for cheast zone was made.

Sep 2017. New metastasis were found in liver during CT analysis - 36x27 mm (V serment), 17 mm (VI segment) and 25 mm (VII segment). It wasn’t found previously when liver zone was scaned (Feb 2017)

Nov 2017. Negative dynamic was found in liver - 49*40 mm (V segment), 25 mm (VI segment) and 37 mm (VII segment). Plus, new met was found in the right ilium wing - 15*5 mm.

Current medicines at the moment:
Sutent (Sunitinib), Lirica (Pregabalin), Finlepsin, Morfin sulfate.

Current diagnosis:
alveolar soft part sarcoma of the tongue soft tissue

Current recommendations:
Undergo general chemotherapy with high doze Doxorubicin and ifosfamide.

Questions:
Q1: Does anybody have a motivated opinion/arguments/experience versus my doctor’s prescribed treatment (he think that general chemotherapy should be used against ASPS metastases in liver now)?
Comment: I do understand that ASPS is very resistant versus general chemotherapy. My main concern – general chemotherapy could be a wasting time, and the metastases will grew up even further, therefore I need to change doctor's prescription and go to Cyberknife, right now..

Q2: Does anybody know experience and/or best practice how to deal with ASPS metastases in liver?
Comment: for example, it could be significantly more effective to treat ASPS in liver via robotic radiosurgery system Cyberknife rather than general chemotherapy.

Q3: Does anybody know cases when tumor metastases grew up in liver very fast (10mm in two month)? If yes, how this challenge was addressed?

Thanks for reading this long text (I think that would be useful for the community) and thank for sharing your ideas for my three questions.

Daria

Thanks for sharing. Asps is indeed very resistant to traditional cytotoxic chemotherapy. Cyperknife is way better option. Stereotactic radiation is most effective when given with single fraction of at least 18 grays. Cryoablation or even open surgey are also valid options. As systemic treatment immunotherapy or tyrosine kinase inhibitors are indeed more sudied than traditional chemotherapy in asps. I havent had liver mets yet, but if I get one I plan to treat it with cryoablation.

The size of the liver mets (and the cumulative amount of the produced necrosis) might be to big for the radiosurgery. If they are resectable and there is a surgeon agreed to resect them, that would probably the better way of dealing with them locally. The rationale of the chemotherapy proposal is the faster than usual speed of growth - faster growing tumors are more chemosensitive, this is why this doctor proposes the traditional cytotoxic treatment that is not usually used in ASPS, but it is still uncertain if there is going to be any benefit? The alternative is the PD-1 or PD-L1 drugs - Keytruda has shown pretty high activity in ASPS patients and we have a sample file of the Keytruda off label request:
http://www.cureasps.org/forum/viewtopic.php?f=76&t=1482
It is here:
Board index Systemic Treatment Immune checkpoint inhibitors ICI (PD-1 and PD-L1 targeting drugs) Keytruda

But the cost is very high if the insurance is not paying, about $9000 USD per a month (it is in Canada, hard to say re. other countries).

Thanks a lot for quick reply and sharing ideas!
After additional discussion with my doctor, the decision had been made. Tomorrow I’ll go to high-doze chemotherapy with Doxorubicin and ifosfamide because:
- Cyberknife refused to operate liver as more than two big metastases in different places.
- Cryoablation option didn’t deeply evaluated as time shortage :/
- Metastases growing fast and force the decision to be made fast as well
Next update expected in January, 2018 right after two courses of chemotherapy ... “good luck to me”
As I understand, beginning next year I will face the following challenging crossroads with different options from bellow table.
--------------------------------------------------:
. . . . .: Met progress/status . . . . . . . . . :
Met . .:------------------------------------------:
Place .: . . growing : . .stable . .: shrinking :
---------------------------------------------------:
Lungs : . . . ? . . . .: . . . ? . . . .: wait/look :
---------------------------------------------------:
. . . .: . . . . . . . . :surgery . . .: . . . . . . . :
Liver : surgery . . .:cyberknife .: wait/look :
. . . .: . . . . . . . . :cryoablation: . . . . . . .:
---------------------------------------------------:
Bone .: cyberknife : cyberknife : wait/look :
--------------------------------------------------:
Some of this options I wish to have, but understand that probability it very low, some of them I have ideas how to address, but there are some that I have no valid ideas/way forward to deal with and need to research/evaluate in order to be prepared. I will try to do my best in order to be prepared, thank you all of you for helping me in this journey.
Thank,
Daria

Good luck to you indeed!
In the mean time keep looking for the PD-1 or PD-L1 clinical trials in Russia. They all should work about the same based on their mode of action.
I found one:
ClinicalTrials.gov Identifier: NCT02908906
unfortunately all the Keytruda clinical trials in Russia are mostly open for RCC, but at least they have a presence in Russia.
So you can contact the Merck in Russia re. off label/patients pay assistance we have done in Canada, you might get a different answer.

Dear Daria, I am so deeply sorry for your ASPS diagnosis, for all of the incorrect diagnoses that were made beginning in 2008, and for all of the challenges, suffering, and increased disease progression that you have experienced on your courageous ASPS journey. I am grateful that you found your way to this Web site and that you have reached out for information. Thank you for your detailed sharing of your ASPS diagnosis, experience, and treatments thus far which is very helpful. Olga and Jussi have offered some excellent input. Regarding treatment of the liver mets, depending on their size and location, Radiofrequency Ablation (RFA) may be a possible minimally invasive treatment option, and was successfully used to destroy our daughter Brittany's single liver met in 2004. Although traditional cytotoxic chemotherapy like Doxorubicin and Ifosfamide has unfortunately usually been unsuccessful for treating ASPS, I am personally aware of at least one patient who had a successful response to it. Each patient is different, and each patient may respond differently to the same drug. As Olga has said, faster growing tumors are more chemosensitive and since your tumors seem to be growing more rapidly than is usual with this typically indolent ASPS disease, Hopefully they will be more responsive to standard chemotherapy. Also, I was wondering if any consideration has been given to trying Cediranib, which is a targeted anti-angiogenic Tyrosine Kinase Inhibitor drug that has VERY thankfully thus far provided our daughter Brittany with 8 and a half years of sustained disease stability and dramatic shrinkage/disappearance of her previous innumerous and widely disseminated mets including an unresectable Life threatening met in the head of her pancreas. Also, as Olga said, one of the promising new PD-1/PD-L1 drugs like Keytruda might be a good systemic treatment option to try to stabilize the progression of your disease and shrink your tumors. If they haven't already been done, you need to have a brain MRI and full body bone scan to ensure that there are no mets in those areas. My VERY best wishes and MOST positive thoughts are with you for a VERY successful response to your chemo treatment, and I will be anxiously awaiting your next update. Take care, stay strong, and know that you are not alone on this journey which all of us on this Forum share with you. With special caring thoughts, healing wishes, warm friendship, and continued Hope, Bonni Hess, mother of now 35 year old Brittany diagnosed 16 and a half years ago at age 19 in July 2001

Olga wrote:Good luck to you indeed!
In the mean time keep looking for the PD-1 or PD-L1 clinical trials in Russia. They all should work about the same based on their mode of action.
I found one:
ClinicalTrials.gov Identifier: NCT02908906
unfortunately all the Keytruda clinical trials in Russia are mostly open for RCC, but at least they have a presence in Russia.
So you can contact the Merck in Russia re. off label/patients pay assistance we have done in Canada, you might get a different answer.

Daria

Hello.

My Name is Debbie and our son was dx'd at 32 years old as well. The top end of most people being diagnosed with a younger persons disease.

I'm so sorry for your having been diagnosed and having to combat ASPS , all the while being pregnant with your 2nd child.
Was your first pregnancy around 2008? Plus or minus 3 or so years?


Olga is truly correct in her advice.. The utmost focus should be to get on an immune therapy , in my opinion. Sooner than later.

Daria - did you see that we have a discussion of the pregnancy associated cases ASPS here:
http://www.cureasps.org/forum/viewtopic.php?f=2&t=1222
if you could test your tumor for Progesterone receptor. You case of the lingual ASPS associated with pregnancy is so similar to the one in the article, make sure to tell the oncologist that a strong Progesterone receptor positivity was found in that published case and try the Progesterone/corticosteroid receptor blocker like Mifeprex (mifepristone?) (emergency unwanted pregnancy terminating drug) or a more pure progesterone antagonist, e.g. onapristone .
Efficacy of the Progesterone Receptor Antagonist Mifepristone for Palliative Therapy of Patients with a Variety of Advanced Cancer Typeshttp://ar.iiarjournals.org/content/30/2/623.full

Daria
Here’s the link
Abstract
https://www.ncbi.nlm.nih.gov/pubmed/20332480/

Full text
http://ar.iiarjournals.org/content/30/2/623.long

http://www.cureasps.org/forum/viewtopic ... 222#p11556

Hello everyone,

Thank you so much for sharing your ideas and providing valuable advices.

Dec 2017. High-dose chemotherapy with Doxorubicin (60 mg / m2, 105 mg per day, 1 day), ifosfamide (2000 mg / m2, 18,000 mg per day) with Mesna (2000 mg / m2, 18000 mg per day) iv 5 days.

Jan 2018. CT scan showed negative dynamic in the liver - approximately 30% increase in volume of all metastasis - most prominent in the V segment - 65 * 55 mm (on Nov 2017 it was 49 * 40 mm). Negative dynamic in lung - most prominent in S1 / 3 segment of left lung - 17 * 20 mm (on Nov 2017 it was 16 * 18 mm)

Mid of Jan 2018. I flew from Moscow, Russia to Miami, USA with the hope to be included in the clinical trial with a combination of Axitinib and Pembrolizumab (Keytruda) - NCT02636725,
https://clinicaltrials.gov/ct2/show/NCT ... SPS&rank=1

At this moment, I have already done some additional examination in the Miami hospital and have got a preliminary confirmation that I am eligible to be included in this program!!! Next week I am planning to do the necessary tests (blood, CT, ECHO) and hope to start medical treatement.

Daria

Very well done Daria! Quick action on your part after you realized that the high doze chemotherapy is not working. Our best regards to Dr. Breelyn Wilky, she is our hero! Good luck with the tests.

Daria
I second Olga’s message .
Gods speed and looking forward to hearing further news .
Love
Debbie

Dear Daria, Thank you for your thoughtful update. I am so sorry, but unfortunately not very surprised that your traditional Doxorubicin, Ifosfamide, Mesna chemotherapy treatment was unsuccessful in shrinking your mets and stabilizing their growth. As I told you in my previous post, traditional chemo has been notoriously unsuccessful in treating ASPS, although each patient may respond differently and I was SO Hopeful that you would have a successful response. I echo Olga's thoughts and words in applauding your having so quickly and pro-actively pursued a new treatment and now already undergoing testing and evaluation for participation in Dr. Wilky's VERY promising Pembrolizumab/Axitinib Trial in Miami. I will be anxiously awaiting your next update which will Hopefully bring good news of your enrollment and participation in the Trial. Take care, enjoy beautiful Miami, and please tell wonderful Dr. Wilky "HELLO" from the Hesses. With special hugs and caring thoughts, healing wishes, and continued Hope, Bonni

I am sorry to bother you, but I would love to know how things are going. When you have time to update.

Dear all!

So, I’ve been on the Keytruda+Axitinib clinical trial (NCT02636725, https://clinicaltrials.gov/ct2/show/NCT02636725) for one and a half years (since February, 2018). The results very positive: the mets in lungs and in the liver reduced significantly, especially in lungs (there was 50 mets, now only 5 mets!! its very impressive!). At this moment (October, 2019), there is only one slightly growing focus in the liver now (approximately 50-60mm in diameter) instead of a lot of diffuse foci scattered through the whole liver.
However, the last CT scan (September, 2019) revealed the new met in the body of the S1 vertebra. The old focus in Th9 vertebra also had started to grow again. I’m planning to perform the irradiation surgery on the S1 (by Varian EDGE, Moscow, http://www.emcmos.ru). My clinical Dr. Trent in Miami confirmed this treatment and will waiting for me to continuing clinical trial (he allowed me to skip one Keytruda injection).
Nevertheless I'm afraid that the next CTscan would show increasing in my mets. And if it happens what do you think could be the next step for me (i.e. what option do I have)?

Thank you for your help!!
Daria