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What radiation regimen do you use to palliate bulky melanoma metastases involving the oral cavity?

In this case, I have a patient with widely metastatic cutaneous melanoma (BRAF wild type, NRAS mutated) who is progressing through pembrolizumab and is being switched to ipilimumab/nivolumab. He has a bulky masseter lesion making it difficult for him to chew. Would you treat with 300cGyx10 or use an alternate hyofractionated regimen?
2 Answers
Mednet Member
Radiation Oncology · Karmanos Cancer Institute - McLaren Proton Therapy Center
Answered on

I like this 9 Gy x 3 melanoma regimen by Dr. Jens Overgaard from Denmark:

https://www.ncbi.nlm.nih.gov/pubmed/4044346

It's an oldie from 1985, but uses roughly the same regimen (9.5 Gy x 3) subsequently found to be the trigger of an abscopal response in a patient progressing on ipilimumab, as reported in the New England Journal in 2012 by MA Postow, et al:

9.5 Gy x 3 is the also dose received by a patient with renal cell cancer, clinically progressing on ipilimumab + nivolumab, who went on to have a complete response, which may have been abscopal:

Timing does matter when combining concurrent ipilimumab with radiation. According to Dr. Marka Crittenden, et al from Portland, ipilimumab should be given before radiation, to decrease the number of regulatory T-cells, which otherwise will inhibit radiation response. Dr. Crittenden's group:

https://www.ncbi.nlm.nih.gov/pubmed/27281029

Most of the studies using PD-1 blockade also show a benefit to concurrent but not sequential XRT, just like we have seen with concurrent chemo but not sequential chemo for H&N and lung cancers.

So when is the best time to treat? I don't know, but in clinic I lean toward after the 2nd cycle of ipi-nivo, like in the renal case above. That way, immune cells are primed and I can still re-eval and treat any bulky surviving lesions after cycle 4. By waiting 6 weeks, prime-boost vaccination may in theory occur (the immune response gets stronger and faster with delayed re-challenge, establishing memory).

PS, I would intentionally AVOID 3 Gy x 10 fx, because of  @Dr. First Last's trial from Stanford (2016 Red Journal) which allowed any dose, but found durable responses only among patients receiving 4 Gy or more per fraction AND to high total BED (4 Gy x 10, 8 Gy x 3, or 12.5 Gy x 4). I have tried 4 Gy x 5 many times, it doesn't work.

The skin seems to tolerate 9 Gy x 3 just fine by the way. I usually give one day off in between, or sometimes treat one day a week, completing in 2 weeks total. I once used it on a bulging 15 cm axillary melanoma that was about to ulcerate through the skin. It didn't :)

Mednet MemberInvited Expert
Radiation Oncology · Fox Chase Cancer Center
Answered on

I have successfully used 6 Gy x 6 twice a week for metastatic melanoma.