While patients with recurrent glioblastoma receiving anti-angiogenic therapy demonstrate significant response rates, the benefit on patient survival is less clear. We assessed whether histogram analysis of diffusion weighted MRI can stratify for progression-free and overall survival. Baseline and 3-6 week post-treatment MRI exams of 91 patients with recurrent glioblastoma treated with bevacizumab were retrospectively evaluated. Histograms of apparent diffusion coefficient (ADC) within the volume of contrast enhancing and nonenhancing T2/FLAIR lesions were analyzed using curve-fit analysis. Overall survival (OS) and progression-free survival (PFS) were assessed using ADC parameters in a Cox proportional hazards model adjusted for clinical variables. Baseline ADC(L)/ADC(M) within nonenhancing T2/FLAIR volume (> or ≤0.64) can stratify OS (HR = 2.24, p = 0.002) and PFS (HR = 1.90, p = 0.005). %ADC(H) within enhancing T1+C volume (> or ≤25 %) can also stratify OS (HR = 0.59, p = 0.034) and PFS (HR = 0.56, p = 0.01). Stratification of patient survival can be improved by merging these two ADC parameters into a single combined ADC factor (HR = 0.17, p < 0.0001). The median OS ratio of patient groups stratified by this combined factor was 2.03, larger than median OS ratio when stratifying by either %ADC(H) within T1+C volume alone (1.3) or ADC(L)/ADC(M) within T2/FLAIR alone (1.86). ADC histogram analysis within both enhancing and nonenhancing components of tumor can be used to stratify for PFS and OS in patients with recurrent glioblastoma.

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Mortality from metastatic cutaneous melanoma is substantially heterogeneous as reflected in three distant metastatic (M1) subtypes with metastasis to skin, subcutaneous tissue, or distant lymph nodes (M1a), conferring nearly half the risk of death compared with distant visceral metastasis (M1c). It remains unknown whether older patients experience the survival benefit from the M1a subtype given a higher overall mortality risk. Surveillance, Epidemiology, and End Result data were retrieved from 1878 metastatic melanoma patients, from 2005 to 2009, with follow-up through 2011. Hazard ratios (HRs) for 2-year overall survival were estimated for M1 subtypes among older (≥65) and younger (<65) patients. Proportional subdistribution hazard ratios (SHRs) were calculated for melanoma-specific and competing risk mortality. For both older and younger patients, worse overall survival was observed for the M1c compared to the M1a subtype [HR: 2.65, 95% confidence interval (CI): 2.02-3.49; and, SHR: 3.36, 95% CI: 2.56-4.41; respectively]. For competing mortality, older compared to younger patients had increased risk in the M1a and M1b subtypes (SHR: 6.07, 95% CI: 1.94-19.0, and SHR: 2.34, 95% CI: 1.08-5.05, respectively). Conversely, when examining melanoma-specific mortality, older patients had decreased risk in M1a and M1b subtypes (SHR: 0.28, 95% CI: 0.14-0.53, and SHR: 0.60, 95% CI: 0.38-0.94, respectively) compared to those under 65 years. The persistent prognostic advantage of M1a among older patients should be considered when calculating the risk-benefit ratio for treatment. Prior reports of a protective effect of older age on melanoma-specific mortality, when based on traditional competing risks analyses, might be explained as an artifact of increased competing mortality risk.

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