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.