Ipilimumab and Stereotactic Radiosurgery Versus Stereotactic Radiosurgery Alone for Newly Diagnosed Melanoma Brain Metastases

Abstract

Use of ipilimumab within 4 months of SRS seems to be safe, with no increase in radiation necrosis or hemorrhage; however, our retrospective institutional experience with this treatment regimen was not associated with improved outcomes.

Improved time to disease progression in the brain in patients with melanoma brain metastases treated with concurrent delivery of radiosurgery and ipilimumab

“…For example, regarding timing, a recent study showed 1-y OS of 42.9% when Ipi was delivered within 14 d of SRS compared to our results of 83% when IT was given within 30 d of SRS. 22 Regarding grouping, our results compare favorably with those of Kiess et al 4 who showed a 1-y OS of 65% and a median OS of 12.4 mo. Our data may have been an improvement on Kiess's results because we had a shorter time between treatments and lower extracranial disease burden.…”

“…[9][10][11][27][28][29][30][31][32] We, along with other authors, believe that this synergy is potentiated by a shorter interval between SRS and IT. 22,35 Mechanistic support for this theory comes from a recent study done in mice which demonstrated that when in vivo melanoma tumor cells were treated with Ipi and RT (10-20Gy/1 fraction) together, the mannose-6-phosphate receptor (MPR) was upregulated and tumor cell growth was significantly reduced compared to IT or RT alone (p D 0.0078). 33 When tumors expressed more MPR, then the effects of Ipi-induced CTLs came to fruition through the binding of their products (granzymes) to their receptors (MPR), thereby killing more tumor cells.…”

“…Several retrospective studies have shown that SRS occurring "within 4 mo," "4 weeks" or "14 d" either before or after IT can reduce the volume of metastases and their results have trended toward improved overall survival; however, statistical significance for OS has been difficult to achieve with small, retrospective cohorts, similarly to our study. 22,35 Other potential explanations for the improved survival in this small cohort of patients compared to historic controls are: First, the LC and CR rates achieved were very high, 94.8% and 38%, respectively, which may have led to fewer CNS deaths. Second, additional RT using 5-8 Gy per fraction for extracranial cancer treatment (SBRT) may have played a role in ongoing antigenic priming, as eight of our patients received this modality during their entire treatment course for treatment of systemic disease.…”

“…9,[15][16][17][18][19] Several retrospective studies have already reported that combining IT with high dose/fraction radiation for MBM improves outcomes particularly when SRS is delivered before or during IT thereby providing an antigenic "primer" for ctivated T cells. 4,[20][21][22][23][24][25] Others suggest a range of time during which concurrent treatment may be helpful, such as ipilimumab infusion within 14 d or within 4 mo of SRS. 22 However, the exact sequencing and timing of the two modalities to achieve maximum benefit are still unclear.…”

“…4,[20][21][22][23][24][25] Others suggest a range of time during which concurrent treatment may be helpful, such as ipilimumab infusion within 14 d or within 4 mo of SRS. 22 However, the exact sequencing and timing of the two modalities to achieve maximum benefit are still unclear. Therefore, in this investigation, we sought to identify if an optimal window of time for IT/SRS co-administration exists that leads to improved brain control.…”