Kevin from California, US (Dx Feb 2012) - RIP Oct 17, 2014

[Olga]

The concern that WBRT might be not helpful is justified, but there are really no other treatment options available except may be going on cediranib right away. There is some info that adding cediranib to radiation improves the outcome in other brain tumours:
http://www.ncbi.nlm.nih.gov/pubmed/24190997
http://www.ncbi.nlm.nih.gov/pubmed/22323823
but it might be difficult to get approved for and what is the availability of the drug.

But I also want to note we do not have any recoded experience (at least I do not remember any) with WBRT used to treat smaller brain mets with or without any radio-sensitizing drug, our patients were treated with it with the bigger well established mets - may be the smaller ones are more radio-sensitive? Or Pazopanib would be able to sensitize them? Although I would really speak to some oncologist skilled in TKI cycles to try to figure out if the radio-sensitizing ability of the TKI drugs is time dependent, i.e. it starts after some period of administration and may be ends later? May be switching to a new TKI would create a window of opportunity as well - there is an article that ? I am afraid though that this data is not available at all or there might be very wide inter-patient variability that makes any stats inconclusive.
I also wanted to point out that gemcitabine might be also used as a radio-sensitizing drug for the brain mets WBRT, and there are the cases when it helped so may be you could discuss it with the oncologist,
some article:
http://www.ncbi.nlm.nih.gov/pubmed/12125975

and we also had a case with the nearly complete resolution of the metastatic ASPS after prolonged treatment with gemcitabine - lung and liver mets, and the patient did not develop the brain mets later - given the very high probability to develop brain mets in ASPS after the person had lung mets for a long time, it is an intriguing observation, the drug is readily available.

[Bonni Hess]

Dear Connie,
As always, Olga has added some excellent insights, perspectives, information, and possible alternative treatment options to consider and explore, and I Hope that you and Kevin will be able to discuss them with the radiation oncologist before you move forward with the WBRT. As Olga has noted, and I completely understand and agree, "The concern that WBRT might be not helpful is justified, but there are really no other treatment options available except may be going on cediranib right away", so you may unfortunately be in a position of having no other choice, but it is important to be as knowledgeable as possible about the risks, potential for a successful WBRT treatment outcome, and the side effects prior to making this very difficult and critically important decision. Take care dear Connie, stay strong, and let Hope continue to lead you through each day on this increasingly challenging journey.
With special caring hugs and thoughts, healing wishes for Kevin, warm friendship, and continued Hope,
Bonni

[Olga]

Connie and Kevin, I was reading the MedLinx digest and came across the article that you might want to read, the subject is how to protect the brain from the radiation-induced cognitive impairment and restore neurogenesis:
Molecular pathways: radiation-induced cognitive impairment.
http://www.ncbi.nlm.nih.gov/pubmed/23388505
It is a research article avail. in free full text here:
http://clincancerres.aacrjournals.org/c ... /2294.long
most of the ideas discussed are just in the pre-clinical or clinical trials stage but you can discuss it with drs if anything could be used right away for Kevin before/during/after he undergoes the WBRT.

[D.ap]

Kevin and Connie

Our hearts and minds are with you in your search for treatment .

All our love
The Josh P family

[wangcns]

Kevin finished up WBRT about two weeks ago. Intense fatigue, lost his hair, headaches but otherwise okay. He stopped the Pazo for a few weeks, which actually contributed greatly to him feeling better, but he's back on the Everolimus and is at half dose for Pazopanib. We do full PET scan again in another month or so, to evaluate if we need to do SBRT on any larger brain mets and check everything else.

I haven't lost hope, but at this point Kevin's ASPS requires a systemic treatment. I wish we could just cut it out of him, but the locations of his mets and the number of them make complete resection of all his mets impossible. We can't even SBRT all his brain mets, there would be too much overlapping. We had Kevin's tumor DNA sequenced, if anyone is interested in seeing his results PM me and I'll email you the PDF. Basically, he shows two mutations TFE3 and RAD51, identified targeted therapies are Crizotinib and Cabozantinib. Don't know if we can get these approved via insurance, but we'll try.

At this point, there's really nothing we can do except stay on top of our scans and make educated guesses about what will shrink or stabilize his mets. I only wish the drugs didn't make Kevin so sick. I read an article written by an oncologist about watching his wife Ruth die from cancer, and one of the phrases he used really stuck with me. "As the cancer gets smarter, the treatments get dumber." Here's to hoping that we one day find a smart way to cure this cancer.

[Jorge]

Hi Connie,

I'm deeply sorry about the side effects from WBRT for Kelvin. Does Kelvin use mannitol to relieve the headache which is caused by the swelling?
It's good to hear Kelvin's back on Pazopanib and Everolimus. My husband George had Pazopanib + Sirolimus (similar to Everolimus) last year before the second laser surgery. We thought it didn't work for the brain mets because new mets found on Oct 23 after taking it for about 1.5 month. But recently, we found those mets existing even on the scans on Aug 07 before taking the Pazopanib combination, about 2mm smaller. Considering the 20-days break before and after laser surgery, I think Pazopanib + Sirolimus worked on the brain mets for George. I wish the Pazopanib and Everolimus combination will also work for Kelvin.

It's good that you managed to have the tumor DNA sequenced and with a result that broadening the options of possible TKIs. So far as I know, Crizotinib and Cabozantinib show much higher BBB penetrability than other VEGFR TKIs, on lung cancer patients. George is also taking Cabozantinib for now to targeting his brain mets and the side effects is much tolerable than Pazopanib. It may be worthy to try them. Good luck to you in the insurance approval.

Best wishes,
Lynette

[wangcns]

So far he's been able to just take some Advil and sleep it off but it does keep him bedridden for a few hours. He was taking Namenda to combat possible cognitive issues stemming from WBRT but he wasn't able to tolerate it, he described it as feeling he was tripping hard (and not in a good way ). Thanks for the words of encouragement, Lynette, I appreciate it.

[Bonni Hess]

Dear Connie,
I am so grateful for your thoughtful update as dear Kevin and you have been so very much in my thoughts and I have been increasingly concerned having not heard from you since the end of March, which I of course understand with all that you have been going through. I am grateful too that Kevin has completed his WBRT but am so sorry for the negative post WBRT side effects that he is suffering and Hope that they resolve and disappear soon. I am holding VERY tight to Hope that the WBRT proves to have been successful in stabilizing the development and growth of Kevin's brain mets with no debilitating cognitive side effects, and my very best wishes and most positive thoughts will be with both of you for his next scans. I am wondering why PET scans are being done rather than brain MRI's and chest/abdominal/pelvic CT's which are much more definitive and accurate since it is my understanding/experience that PET scans only show possible tumor activity and are notoriously unreliable often showing erroneous postive or negative results as we experienced with Brittany nine years ago when a PET scan showed possible tumor re-occurrence in her resected tumor bed. Based on the PET scan results (which we ultimately found were erroneous), Brittany underwent an interstitial laser thermotherapy surgery to remove the alleged tumor re-occurrence, but it was found there was thankfully no tumor re-occurrence and the surgery had been totally unnecessary!!
I agree that Kevin definitely needs a systemic treatment that can cross the blood brain barriar to try to stabilize the aggressive progression of his disease and to shrink/destroy his multiple unresectable/untreatable brain mets. I am grateful that his tumor tissue testing shows two identified targeted drugs which may be effective for him and I encourage you to research and pursue treatment with the one which seems most promising as soon as possible. Was Cediranib considered as a possible effective targeted drug for him based on the tumor tissue testing? According to a recent post by Yossi Landesman on this Forum, Cediranib is apparently now available in Clinical Trial at Dana Farber so insurance coverage would not be an issue.
I will be anxiously awaiting your next update when your time and the situation allow. In the meantime, please give yourself and Kevin special hugs from all of us Hesses dear Connie, and know that you are both being held very close in our hearts and our most special thoughts.
With deepest caring, healing wishes for Kevin, much love, and continued Hope,
Bonni

[wangcns]

Hey all,

We just saw Dr. Federman yesterday and reviewed Kevin's brain MRI from last Tuesday. The WBRT does not appear to have been effective, as there is no change in the mets, some are slightly larger, and there are also new lesions. Of course, there is a good chance those mets were already present during the previous scan, just not large enough to see or perhaps the vertical slice didn't catch it, but Noah thinks this is evidence that Pazopanib and Everolimus is not effective in treating the brain mets. We have to discontinue Everolimus anyway, because Kevin is unable to tolerate it. It causes angry red skin ulcers to appear everywhere. Before, it was just his back, but they've been popping up on his arms and even his head.

Cigna is denying us Crizotinib, even though UCLA submitted the FoundationOne paperwork to prove that it could potentially be an effective treatment for Kevin. This is a tough situation, because the FDA doesn't approve Crizotinib for ASPS and like it always is with ASPS, there is no large body of evidence that supports its use to treat ASPS. We're going to work with a lawyer to see how best to resolve this situation, but in the meantime we are going to try and see if we can get in on a Trabectadin clinical trial/compassionate care.

Kevin is doing okay, he's still very fatigued from the radiation (it's been about a month since he finished) and in the last week he's developed severe nausea and headaches. We're uncertain if it's the side effects of radiation or because of the brain tumors, hard to say at this point. Kevin's going to continue with the Pazopanib until we can get switch to either the Crizotinib or find a way to get Trabectadin. He's going back on some steroids, AVN be damned, and hopefully we will see some abatement of the nausea and headaches.

[Bonni Hess]

Dear Connie,
It is so very kind and thoughtful for you to write to update the Board in the midst of all that Kevin and you are going through. I am so deeply sorry and saddened that the WBRT has thus far been unsuccessful in shrinking/destroying Kevin's multiple brain mets and preventing the growth of new ones, although sadly this is not unexpected since based on my personal knowledge from extensive research and closely following anecdotal ASPS patient treatment experiences with WBRT, WBRT has unfortunately not been successful for ASPS. Regarding the denial for Crizotinib, based on my personal knowledge of ASPS patient Crizotinib treatment experience, it too unfortunately does not seem to have proven to be very effective for ASPS. Tragically, a young woman who was previously treated with Crizotinib and whose mother formerly actively participated on this Board, recently lost her very courageous seven year battle following several failed treatments including Crizotinib. Rather than pursuing Crizotinib, have you considered Cediranib which has shown success for some ASPS patients including Brittany, or perhaps Cabozantinib (Cometriq). I know that there is currently limited results data available for Cabozantinib, but we do have two patients on this Board ( MJ and Mario) who are being treated with it who you could perhaps contact to discuss their Cabozantinib experience/results thus far.
My heart is breaking for all of Kevin's radiation/brain met caused headaches, vomiting, and suffering which I know far too well from Brittany's severe brain swelling experience following her first Gamma Knife which unfortunately failed because the treated tumors were already too large, and the tumors continued to grow and create swelling until they were finally successfully resected. I Hope that the resumption of Kevin's steroid regimen will help to reduce and alleviate his radiation/tumor caused swelling and suffering. Steroids were the only thing that worked for Brittany to help resolve the severe headaches and vomiting, and even then she sometimes additionally needed emergency hospitalization to receive IV steroids, anti-nausea meds, Dilautid for the pain, and re-hydration. What is the "AVN" that you referred to? Is Kevin taking Decadron or Prednisone? Decadron worked much better than Prednisone for Brittany, but of course high dose long term steroid treatment such as Brittany was on for five very difficult months creates it's own set of problems, so Hopefully an effective systemic treatment will be found for Kevin and it will be able to shrink/destroy Kevin's brain mets so that he will not need long term steroid treatment.
Please take care dear Connie, give Kevin and yourself gentle hugs from all of us Hesses, know that you are both held very close in our hearts and most caring thoughts always, and keep in touch as you are able.
Sharing your concern and great heartache with deepest caring, healing wishes for dear Kevin, warm friendship, love, and continued Hope,
Bonni

[Jorge]

Connie,
I'm so sorry that the Gama Knife so far can't destroy or shrink the brain mets and Kelvin is having severe nausea and headaches. From the experience of the first Gama Knife George had, mannitol is much better in relieving nausea and headaches caused by swelling. It's really helpful. Please talk about it with your Doctor if it can be used to relieving Kelvin's sympton.
Bonnie has provided very good and detailed recommendations. Hope you can move on and get approval to switch to some other TKI soon.
Take care and be srtong.

Lynette

[Amanda]

Hello
Here is a link from our researcher about Ced trial. there are links to contact them thru here... http://www.cureasps.org/forum/viewtopic.php?f=45&t=887

I also got a phone number into a person named Lola and i didn't talk to her but she is with Cigna legal and deals with approvals 614-899-4393
as far as i can tell she is one of two ladies that deals with approvals.

I do not want to over step so let me know what i can do to help you <3

[wangcns]

Thanks for all the support and advice, as always everyone.

Bonnie - Thanks for the thoughtful and kind words, Bonni. AVN (avascular necrosis) AKA osteonecrosis, basically bone tissue death. From what I can tell, it's fairly common in cancer patients who have been treated with steroids and radiation. Kevin's right shoulder bone has started to die, but luckily it's not in a weight-bearing location. She did warn that resumed steroid use may lead to further bone tissue death, but when steroids are needed, they're needed. Kevin's taking decadron and it seems to be working. We've been corresponding with F, we were pretty sad about K, but the attempt to get on crizotinib or cabozantinib is based on the gene-sequencing results, which are different from ASPS patient to patient. Cediranib is a VEGF inhibitor, same as pazopanib, and Kevin has seen moderate success with it in some areas, specifically the sacrum tumor (the pazo definitely shrank it during the three months before he received SBRT for it) but other tumors, such as certain ones in his lungs and these new ones in his brain, are clearly not responding. I'd try cediranib, but I agree with our doctors that it might be a good idea to try a different class of drug since the pazo has had limited success. None of these drugs have shown good long-term success, but Kevin has too many tumors in too many locations to resect, so we are squarely in the systemic treatment boat now. Cometriq (cabozantinib) is not covered, the oncologist we saw today for a potential clinical trial wrote us out a prescription but it didn't get past Cigna.

Lynette - I will definitely ask about mannitol, though Kevin has already finished his radiation and his dose of decadron. I'm sure there will be a next time.

Amanda - thank you so much! I spent the afternoon on the phone with Cigna, and am pushing on a few other things. If that doesn't pan out, I will definitely try the number you found for me and thanks for the cediranib info.

Here's where we're at right now:

-Uncertainty about recent brain MRI; apparently it's difficult to read and nobody can say with any clarity whether there are more mets or whether they are bigger (swelling?). Arranged a meeting with his two rad oncs, his one in UCLA and the one who treated him closer by here in Newport Beach, to have them make the call on whether they feel WBRT did anything. The radiologist who did the read said she feels like there's no change from the March brain MRI, so until we have consensus on what exactly is going on in his brain, we are stuck.

-Blocked by insurance - mainly the inability to get crizotinib and cabozantinib. Cigna won't pay for our gene-sequencing either, though Foundation Medicine apparently is very used to this and is helping us appeal. Our onc began the peer-to-peer review process and has been asked to put together a report, but this takes time. I'm hoping this will pan out because I spent two hours on the phone with Cigna today (the reps were very kind. the system still makes me seethe with rage) and the only way they'll make an exception for Kevin is by our doctors convincing them this drug is medically necessary. I'm still waiting to see if secondary insurance will approve anything.

-Clinical trials - Kevin has active brain mets (or maybe he doesn't?) which precludes him from many clinical trials. We're hitting up the researchers anyway, just to see if there's anything we can do.

[D.ap]

Hi Connie and Kevin

Thank you for the update in such a difficult time.
After taking the steroids can that possibly give a better MRI with the reduced swelling ?
I hope that today brings Kevin feeling better!

Love
Debbie

[Amanda]

HI Connie,
I also have Cigna an i called the Cancer Treatment Centers of America and it seems that take Cigna...

They do the treatment i need done since Dr L an Dr Suh are not responding to the disks from my Onc i am looking into treating there from now on!

Have you looked into the treatments there yet?