Browsing by Author "Mahadevan, Anand"

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    Dosimetric analysis of the alopecia preventing effect of hippocampus sparing whole brain radiation therapy.
    (Radiat Oncol, 2015-11-26) Mahadevan, Anand; Sampson, Carrie; LaRosa, Salvatore; Floyd, Scott R; Wong, Eric T; Uhlmann, Erik J; Sengupta, Soma; Kasper, Ekkehard M
    BACKGROUND: Whole brain radiation therapy (WBRT) is widely used for the treatment of brain metastases. Cognitive decline and alopecia are recognized adverse effects of WBRT. Recently hippocampus sparing whole brain radiation therapy (HS-WBRT) has been shown to reduce the incidence of memory loss. In this study, we found that multi-field intensity modulated radiation therapy (IMRT), with strict constraints to the brain parenchyma and to the hippocampus, reduces follicular scalp dose and prevents alopecia. METHODS: Suitable patients befitting the inclusion criteria of the RTOG 0933 trial received Hippocampus sparing whole brain radiation. On follow up, they were noticed to have full scalp hair preservation. 5 mm thickness of follicle bearing scalp in the radiation field was outlined in the planning CT scans. Conventional opposed lateral WBRT radiation fields were applied to these patient-specific image sets and planned with the same nominal dose of 30 Gy in 10 fractions. The mean and maximum dose to follicle bearing skin and Dose Volume Histogram (DVH) data were analyzed for conventional and HS-WBRT. Paired t-test was used to compare the means. RESULTS: All six patients had fully preserved scalp hair and remained clinically cognitively intact 1-3 months after HS-WBRT. Compared to conventional WBRT, in addition to the intended sparing of the Hippocampus, HS-WBRT delivered significantly lower mean dose (22.42 cGy vs. 16.33 cGy, p < 0.0001), V24 (9 cc vs. 44 cc, p < 0.0000) and V30 (9 cc vs. 0.096 cc, p = 0.0106) to follicle hair bearing scalp and prevented alopecia. There were no recurrences in the Hippocampus area. CONCLUSIONS: HS-WBRT, with an 11-field set up as described, while attempting to conserve hippocampus radiation and maintain radiation dose to brain inadvertently spares follicle-bearing scalp and prevents alopecia.
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    Ipilmumab and cranial radiation in metastatic melanoma patients: a case series and review.
    (J Immunother Cancer, 2015) Schoenfeld, Jonathan D; Mahadevan, Anand; Floyd, Scott R; Dyer, Michael A; Catalano, Paul J; Alexander, Brian M; McDermott, David F; Kaplan, Irving D
    BACKGROUND: Ipilimumab improves survival in metastatic melanoma patients. This population frequently develops brain metastases, which have been associated with poor survival and are often treated with radiation. Therefore, outcomes following ipilimumab and radiation are of interest, especially given case reports and animal studies suggest combined treatment may generate abscopal responses outside the radiation field. FINDINGS: We reviewed sixteen consecutive melanoma patients who received 1 to 8 courses of radiation, with a sum total of 51, systematically evaluating abscopal responses by following the largest extra-cranial lesion. We also reviewed other series of patients treated with cranial radiation and ipilimumab. Our patients received between 1 and 8 courses of cranial radiation. Four patients received radiation concurrently with ipilimumab. Median survival was 14 months, and 17 months in patients initially treated with SRS. Interestingly, after radiotherapy, there was a 2.8-fold increased likelihood that the rate of extra-cranial index lesion response improved that didn't reach statistical significance (p = 0.07); this was more pronounced when ipilimumab was administered within three months of radiation (p < 0.01). CONCLUSION: Our experience and review of recently published series suggest ipilimumab and cranial radiation is well tolerated and can result in prolonged survival. Timing of ipilimumab administration in relation to radiation may impact outcomes. Additionally, our results demonstrate a trend for favorable systemic response following radiotherapy worthy of further evaluation in studies powered to detect potential synergies between radiation and immunotherapy.
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    The role of whole brain radiation therapy in the management of melanoma brain metastases.
    (Radiat Oncol, 2014-06-22) Dyer, Michael A; Arvold, Nils D; Chen, Yu-Hui; Pinnell, Nancy E; Mitin, Timur; Lee, Eudocia Q; Hodi, F Stephen; Ibrahim, Nageatte; Weiss, Stephanie E; Kelly, Paul J; Floyd, Scott R; Mahadevan, Anand; Alexander, Brian M
    BACKGROUND: Brain metastases are common in patients with melanoma, and optimal management is not well defined. As melanoma has traditionally been thought of as "radioresistant," the role of whole brain radiation therapy (WBRT) in particular is unclear. We conducted this retrospective study to identify prognostic factors for patients treated with stereotactic radiosurgery (SRS) for melanoma brain metastases and to investigate the role of additional up-front treatment with whole brain radiation therapy (WBRT). METHODS: We reviewed records of 147 patients who received SRS as part of initial management of their melanoma brain metastases from January 2000 through June 2010. Overall survival (OS) and time to distant intracranial progression were calculated using the Kaplan-Meier method. Prognostic factors were evaluated using the Cox proportional hazards model. RESULTS: WBRT was employed with SRS in 27% of patients and as salvage in an additional 22%. Age at SRS > 60 years (hazard ratio [HR] 0.64, p = 0.05), multiple brain metastases (HR 1.90, p = 0.008), and omission of up-front WBRT (HR 2.24, p = 0.005) were associated with distant intracranial progression on multivariate analysis. Extensive extracranial metastases (HR 1.86, p = 0.0006), Karnofsky Performance Status (KPS) ≤ 80% (HR 1.58, p = 0.01), and multiple brain metastases (HR 1.40, p = 0.06) were associated with worse OS on univariate analysis. Extensive extracranial metastases (HR 1.78, p = 0.001) and KPS (HR 1.52, p = 0.02) remained significantly associated with OS on multivariate analysis. In patients with absent or stable extracranial disease, multiple brain metastases were associated with worse OS (multivariate HR 5.89, p = 0.004), and there was a trend toward an association with worse OS when up-front WBRT was omitted (multivariate HR 2.56, p = 0.08). CONCLUSIONS: Multiple brain metastases and omission of up-front WBRT (particularly in combination) are associated with distant intracranial progression. Improvement in intracranial disease control may be especially important in the subset of patients with absent or stable extracranial disease, where the competing risk of death from extracranial disease is low. These results are hypothesis generating and require confirmation from ongoing randomized trials.