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    Anyone know of study findings related to brain mets and immunotherapy? Are PD-1 and IPI effective at motivating the immune system to respond to mets in the brain? I’ve seen that many of the trials exclude patients with brain mets–the reason for that? If one develops brain mets after the trial is in progress are you cast off….

    Catherine Poole

    Trials usually exclude brain mets until they have been resolved with SRS radiation. They you can join a trial. Getting something across the blood-brain barrier is very difficult. I haven’t seen much evidence of the current therapies doing that. STill seems like radiation is the best therapy for brain mets.


    The oncologist at the University of Michigan I am working with and others whose research I have read consider immunological therapy to be successful with brain mets. The term often used is synergistic effect. The blood brain barrier is not the main consideration here. Whether the ipi, for instance, gets to the brain or not, the ipi allows the immune system to stay heightened, and it is the immune system that does the work on the cancer present in any location in the body. There is no brain barrier to the function of the immunological system.

    There is a small literature developing on the timing of immunological infusions and brain radiation. If I can find anything, I’ll post it. Should the procedure to eliminate the tumor take place before ipi or after ipi has begun,for instance? My oncologist deliberately withheld SRS until the ipi had already been doing its work for over a month, even though the two brain tumors I had were definitively spotted. I confirmed with Dr. Chapman at Sloan Kettering by way of second opinion whether this was something he would have recommended, and he felt it was a reasonable approach given the interaction between SRS and ipi. So I went ahead with the delay of SRS for these reasons with a good deal of confidence that the combination treatment and its timing could pay dividends. Still dong well almost six months later.

    Catherine Poole

    It is an interesting theory, and there was a small study showing one of the BRAF drugs helping with brain mets too. But unfortunately, these theories aren’t well proven in the literature by vast numbers of patients having this experience. The new radiation techniques are highly successful to zap brain mets and that is a good step forward. Whether IPI and radiation sequenced a certain way is best, there was one study out of Memorial Sloan Kettering, but it was a small number. I hope things continue on a good path for you Frank.


    I have some experience with brain mets, ipi, and radiation.

    My first met was discovered in my left lung in Sep 2011. I had it removed through surgery (Oct) and then had round 1 of ipi (Dec/Jan). I was NED until brain met #1 was discovered in June 2012 (GammaKnife in July to treat). Round 2 of ipi in Sep 2012. Then craniotomy #1 in Nov. I was NED until April when they found a recurrence (five months . . . so close to PD-1). I finished CyberKnife on Tuesday (five days of treatment) and we will wait and see. I don’t think my insurance will cover round 3 of ipi (and not sure if my med onc would even recommend).

    Good luck to you all.


    My understanding lines up with Franks.

    Basically the treatment antibodies themselves do not cross the blood-brain boundary but the activated T-cells they stimulate the immune system to produce can and do cross over but I’ve no clue as to how effecient that crossover is.

    I believe one of the webinars here shows that for IPI and I’ve seen the effect documented for TIL at the NCI.

    Now that IPI has been widely out and about for a couple of years, I’d be willing to bet money that someone is combing thru the IPI data available from some of the larger clinics that have a high melanoma traffic. I’d further bet a carefully constructed retrospective study could easily glean IPI’s effects on brainmets (onset timing and resolution) if they are statistically significant. As Catherine said, there is nothing obvious jumping out concerning IPI and brain met response so, to me, that implies brain met response is a subset of IPI’s overall response. Seems this would be great topic for a thesis.

    But number crunching aside, every little bit helps and provides hope in this battle. I’m rooting for those T-cells crossing over and doing their thing.


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