Any experience with targeted therapy for BRAF V600E mutated tumor(s)?

Update from yesterday: my surgeon, Dr. Mohammed Qaisi was very open to not just gene sequencing my sample, but moving forward with potential BRAF/MEK inhibitors. He wasn't very aware of that option as a neoadjuvant treatment, but said he thought a surgical oncologist friend of his at Rutgers may have been involved in an earlier clinical trial or some other research with them. Dr. Qaisi was not a fan of the pathology report from my biopsy as the author didn't specify a subtype, and my prior oral surgeon didn't send over imaging. Based on the CBCT we took yesterday, he's fairly confident my amelo is conventional, but it looked like it could be unicystic.

I've reached back out to my prior doc to have her reach back out to the lab to basically re-write the pathology report AND conduct next-gen sequencing on the sample. Follow up with Dr. Qaisi is June 1 but, for now, I'm breathing a big sigh of relief that he's in my corner.

@phillisi88 I'd like to add my welcome. I'm tagging @tomschwerdt to make sure he sees your message directed to him.

@colleenyoung thank you for tagging @tomschwerdt, but I haven’t seen a response or post from him in some time. I hope he’s alright.

Tom, if you’re out there, I need some advice. My sequencing came back positive for BRAF, but my surgeon wants to do just that. He cited a colleague of his, who used to be at UPenn and is now at Rutgers, who conducted some summary research on inhibitor treatments for ameloblastoma and large cell granuloma. My doctor believes that the most likely outcome is necrosis of the center of the tumor, but remaining viable cells on the periphery which would still require a complete resection. I’ve reached out via email to the doctor at Rutgers to get his thoughts on a few articles which had been published in the time between his summary article and now.

I’d love to hear from you directly if you’re able.

All the best!
Phil

Hi, Phil!

Life's been busy and I hadn't gotten back to Mayo in awhile. Do you happen to know which BRAF mutation it is? Most jaw ameloblastomas are BRAF V600E, which is what I have and for which there are targeted chemotherapy options (developed for other cancers, of course).

As I've said before - surgeons are comfortable with surgery as a treatment and generally will recommend surgery. More flippantly "Surgeons gonna Surgery."

The "standard of care" for ameloblastoma is radical surgery and has been for a long time. The currently preferred version is a radical resection and fibular flap. Because ameloblastoma is so darn rare, there's not much motivation to explore non-surgical treatments.

That's why I asked my primary care physician for a referral to MD Anderson when my ameloblastoma came back after 15 years* MD Anderson is a top cancer hospital globally and only about a 3 hour drive from here. They are willing to be the cutting edge of treatment. They are also VERY patient-centric. They have treated me very well.

I had also read the research myself and I knew I wanted to try targeted chemotherapy. MDA gave me a full set of tests. The team had a dentist, an oral surgeon and an oncologist. I was told that surgery was the standard of care. I listened carefully to everything they had to say and told them that I'm not comfortable with the surgery, and handed over several research papers on using targeted chemotherapy - 5 pills a day. I then requested we try it first. The pain in my jaw went away in no more than a week. I've been going back every 3 months for a followup and they mail me the medication.

Fortunately, my insurance covered the (quite expensive) medication, and I found a program through the manufacturer which covered my copay.

Did I have some side effects? Absolutely. Most of the impact was fatigue and heat intolerance. I spiked a very high fever early on, but it was controlled with Tylenol, which I no longer needed after a day or two.

CT scans showed that the tumor shrank for awhile (bone regrowth) then stabilized. While I'd hoped for complete remission, I'm satisfied that I took this route with treatment.

In my opinion, there is little downside to trying targeted chemotherapy first. If needed, you can get the surgery later.

I'm sure there are many great oncologists out there, but I can only speak to my own experience. I highly recommend my oncologist at MD Anderson: https://faculty.mdanderson.org/profiles/neal_akhave.html

You need to decide what approach is right for you. I suggest at least getting a second opinion with an appropriate oncologist - ideally one who has treated ameloblastoma non-surgically.

*Yep, this is my second round. Original oral surgeon wanted to do radical resection and titanium plates. After research and much discussion, we agreed on enucleation and currettage (basically cut/scrape out the pocket) followed by flushing the pocket with Carnoy's solution to kill residual cells and I would retain my original jawline. There was no targeted therapy available back then.

Immediately before the surgery the surgeon told me he wasn't going to use the Carnoy's and would just flush with distilled water, hoping osmotic pressure would rupture the remaining ameloblastoma cells. I didn't really have a choice at that point, so I went ahead with it.

After recovery, autologous bone transplant and 2 dental implants I had full function in my jaw and didn't have to do anything for another ~15 years. In my book, that's a win, especially because targeted chemotherapy became available in the meantime.
https://en.wikipedia.org/wiki/Carnoy&

I've attached a meta-study of targeted treatment of ameloblastoma. There may well be something newer, I haven't looked recently.

@tomschwerdt thanks so much for replying! I’m BRAF V600E positive. I told the surgical oncologist that I wanted to explore the medicinal option first, and he seemed open. At my follow up this past Monday, he said he’d reached out to his colleague at Rutgers who doesn’t think the medicinal option is worth it. Yes, we see necrosis in the center of the tumor, but the periphery still has viable tumor cells. For what it’s worth, I think the surgeon is a pretty good one.

My mother-in-law, who used to work in a dental office, leaned into her network and got me in with another surgeon for a second opinion. I’ll go through the same things with him (first consult on July 2). But I’d be lying if I said I wasn’t chasing the non-surgical option. I have access to MD Anderson through their partnership with RUSH here in the Chicago area. And I’ll be reaching out to them after coming home from vacation.

My questions for you: 1) how long were/have you been on the medicinal regimen? 2) When you say you’re satisfied, how much (rough percentage) did you see it shrink? 3) If this option existed, would you have done this the first time around?

This is my first go round with this booger. And I’m really (un)lucky because it’s located at my first premolar, and it’s already moved that tooth. Given its size (not “huge,” but not small), and “adequate” margins, the FFF surgery would see me lose 6-7 teeth aka half of my mandible. I’d be lying if I said I wasn’t chasing the non-surgical route out of fear. I also simply don’t see a downside to it. If it doesn’t work…cool, now I lose 8 teeth, that’s still half my mandible. Whereas, if it does, maybe we get by with only an enucleation procedure.

My wife prefers the surgery, she’s worried about prolonging it and seeing the thing break through my jaw bone. My fears are multifaceted, I don’t want to put our kids (2 & 4) through seeing their dad with a feeding tube for a week or more, and it’s location suggests to me that I won’t ever look the same after surgery (vain as that sounds). FWIW, I haven’t spoken to my PCP yet.

I, too am interested in responses to targeted therapy for BRAF v600e positive tumors. My husband has metastatic lung cancer. A liver biopsy was performed at Mayo Clinic (Jacksonville), which pathology of the lesion was deemed sarcomatoid carcinoma. He is 78 y/o with hypertrophic cardiomyopathy as well as multiple sun damage type lesions on skin. This worries me as common side effects include a serious skin rash as well as less commonly, ill effects on the heart. Has anyone with the sarcomatoid carcinoma of lung responded to targeted therapy and avoided serious side effects?

@phillisi88

Phil,

I still highly recommend consulting an oncologist, preferably one with experience treating ameloblastoma with targeted therapy. Specifically ask them about targeted therapy and express your concerns about the surgery.

Here's how I see it:

This is typically a very slow growing tumor with little need to rush into treatment unless you're having significant negative effects from the tumor.

Choose surgery and you're probably* done. You won't look the same, your jaw won't function the same, you will have a long recovery while you go through various therapies to relearn eating, speaking, etc. You may have permanent sensation loss in part of your face due to losing the nerve which runs through the jawbone. Some folks have described their recovery process and were generally satisfied. One person here had a rejection of the fibula transplant, a possibility which was never mentioned by my oral surgeon when I asked for details on the surgery.

Choose surgery first and there's no going back.

Chose the targeted chemotherapy and you are likely to have side-effects, but not nearly as bad as classic chemotherapy. It's taking pills, not getting an IV in the hospital.

Choose chemotherapy first and if it doesn't work for whatever reason, you can go have the surgery.

Either way, you're going to need to continue monitoring that jaw for years.

How my tumor in particular responded shouldn't be the deciding factor. From what I recall of the literature I read, the majority of BRAF V600E ameloblastoma tumors went away completely with the targeted chemotherapy. The majority of those who didn't have full remission still responded, but not completely. I'm in the latter category.

It's possible my tumor is entirely gone/dead - but I can't know that unless there is exploratory surgery/biopsy. The CT doesn't actually show tumor shrinkage, it's showing bone regrowth.

Perhaps my jaw bone just stopped regrowing without filling in fully. That's what happened with my original conservative surgery - bone stopped growing and I ended up getting a bone transplant from far back in my jaw.

*Why probably? There's a certain percentage of ameloblastomas which will regrow anyway, even with the full resection and 1 cm (or more) margins. It's been awhile since I scoured the data, so I can't give you a firm number. In addition, published numbers are likely to be low since most followups on recurrence end no more than 5 years after the surgery.

I was pronounced cured 5 years after my original conservative surgery and told that I didn't need to come back for monitoring anymore. My ameloblastoma recurring 15 years after the surgery wouldn't be captured in any published statistics.

@phillisi88

Hey, Phil! Just checking in.

@tomschwerdt hey Tom, thanks for reaching back out!

The surgeon at UI-C was very much open to, and submitted a referral for, me to meet with a medical oncologist to discuss BRAF treatment as a neoadjuvant therapy. He, the surgeon, has not been part of treating any amelo patients in this way, but said “there’s no harm in trying.” On the other hand, he’s of the opinion that tumor shrinkage is likely not to result in any treatment other than FFF to “cure” the tumor.

I meet with the oncologist on July 22, then have a follow up with the surgeon on July 30. Regardless of the outcome of the oncologist consult, I’ll be receiving treatment here at UI-C. The comfortability with the staff, even after a single visit, was felt almost immediately. I’m excited to at least have the conversation with both doctors here.

This new surgeon did mention that he’d hoped the BRAF inhibitor therapy would’ve been an end all be all for amelos, but that hasn’t been borne out. Part of me thinks that’s multifaceted 1) people don’t dig into treatment options prior to surgical consultation, 2) there aren’t enough people with amelos to begin with, and 3) surgeons do surgery. From my reading, and I’m hoping the oncologist is well versed, most patients see pretty extensive bone regrowth/tumor shrinkage and are able to minimize surgery with it.

The unknown, however, is long term. We know amelos can recur after 15+ years, but this medical route hasn’t even been available that long, let alone have enough clinical use to determine long term effectiveness. Recurrence after FFF is low, but not 0%. As apprehensive as I am now for a primary amelo, I’d be even more so for a recurrence. That would simply be unacceptable to me. So, anything I can do to minimize that outcome is my preferred approach.