Dibaj, Seyedeh

AbstractBackgroundAdult medulloblastoma (MB) is rare, and management guidelines are largely based on pediatric clinical trials and retrospective series. Limited data exist with respect to clinical characteristics, prognostic factors, and outcomes based on first-line treatments.MethodsTwo hundred adults with MB seen at a single institution from January 1978 to April 2017 were identified and followed for a median of 8.4 y (7.1, 10.3).ResultsPatient’s median age at diagnosis was 29 y (18, 63). One hundred eleven (55.5%) were standard-risk, 59 (29.5%) were high-risk, and 30 (15.0%) were indeterminate. Most received post-operative radiation (RT) (184 [92.0%]), and 105 (52.5%) received first-line chemotherapy. Median overall survival (OS) was 8.8 y (7.2, 12.2) and median progression-free survival (PFS) was 6.6 y (4.9, 11.2). High-risk patients had inferior OS (Hazard ratio [HR] = 2.5 [1.5, 4.2], P = .0006) and PFS (HR = 2.3 [1.3, 3.9], P = .002) compared to standard-risk patients. Age, sex, and metastatic disease were not associated with survival. After adjusting for risk status, those who received RT plus adjuvant chemotherapy had superior PFS compared to RT plus neoadjuvant chemotherapy [HR = 0.46 (0.22, 0.95), P = .0357]. Within a subgroup for whom detailed clinical data were available, those who received RT plus adjuvant chemotherapy had improved PFS compared to RT only [HR = 0.24 (0.074–0.76), P = .016]. The substitution of cisplatin for carboplatin and the elimination of vincristine did not negatively affect outcomes.ConclusionThis is the largest single-institution retrospective study of adult MB to our knowledge and identifies standard-risk status, first-line RT and adjuvant chemotherapy as factors associated with improved outcomes.

Abstract BACKGROUND While glioblastoma (GBM) is more prevalent in males, studies show that females with GBM tend to have longer overall survival (OS) than males. Pretreatment neutrophil to lymphocyte ratio (NLR) has also proven to be prognostic in GBM, with lower NLR having favorable outcomes. This secondary analysis of a prospective randomized trial of proton vs. photon intensity modulated radiotherapy aims to explore the interaction of gender and NLR on GBM outcomes. METHODS Analysis was performed on the full patient population. Kaplan-Meier methods estimated OS with censoring at last follow-up for those who were alive. Univariate (UVA) and multivariate (MVA)Cox proportional hazards models assessed predictors of OS. RESULTS Of 90 patients, 77 were included (43 males; 34 females) with median age of 52 years (range: 26–82 years). Median OS was longer for females than males (30.7 vs 18.2 months, p=0.004). On UVA, patients with NLR below median value (NLR= 3.1) tended to have longer OS than those above median, though not meeting statistical significance (23.1 vs. 17.9 months, p=0.051). Difference in OS was statistically significant in females (OS 36.4 months NLR >median vs. 16.7 months NLR< median, p=0.002), but not in males (OS 17.8 months NLR >median vs. 19.1 NLR< median, p=0.95). MVA analysis was consistent, with female gender predicting reduced hazard ratio (HR) (0.28, p=0.034) and females with below median NLR showing a reduced HR over those with above median (0.28, p=0.005). Again, males did not benefit (HR 0.90, p=0.77). CONCLUSION Consistent with prior publications, females and all patients with lower pre-treatment NLR with newly diagnosed GBM had longer OS. However, combining these two factors revealed that the benefits from lower pre-treatment NLR were conferred only in females with no impact on males. This different impact of NLR between genders may suggest innate immune differences in gender during response to malignancy.

Abstract PURPOSE To compare tumor progression based on clinical radiological assessment and on Response Assessment in Neuro-Oncology (RANO) criteria between GBM patients treated with proton radiotherapy (PT) vs. photon intensity modulated radiotherapy (IMRT). METHODS Eligible patients were enrolled on the described prospective phase II trial and had MR imaging at baseline and follow-up beyond 12 weeks from treatment completion. ‘Clinical’ progression was based on a radiology report of progression in combination with changes in treatment due to suspected disease progression. A single blinded observer applied RANO criteria to determine the RANO-based tumor progression. RESULTS Of 90 enrolled patients, 66 were evaluable, with median follow-up of 19.8 (Range: 3.2–65.1) months; median of 22.6 months for PT (n=25) vs. 18.9 months for IMRT (n=41). Median time to progression (TTP) was 7.9 months based on clinical progression criteria (8.1 months IMRT, 6.3 months PT) and 7.2 months (7.3 months IMRT, 5.7 months PT) by RANO criteria (p=ns for all). Median ‘clinical’ progression-free survival (PFS) was 8.7 (Range: 6.4–11.1) months; 8.9 months IMRT vs. 8.7 months PT (p=0.065). Median RANO PFS was 8.3 (range, 5.8–11.6) months: 8.3 months IMRT vs. 6.9 months PT (p=0.226). There were 14 discrepant cases: 3 had progression based on ‘clinical’ but not RANO criteria, and 11 had progression based on RANO but not ‘clinical’ criteria. CONCLUSION Based on this secondary analysis of a randomized trial of PT vs. IMRT for GBM, there was no difference in tumor progression relative to treatment technique used. There was no statistical difference in PFS noted between clinical and RANO-based assessments, but RANO criteria identified progression more often than clinical assessment, and TTP was shortened with the use of RANO criteria alone. Further development of tumor assessment tools that improve consistency and accuracy of determining tumor progression are needed to guide therapeutic trials in GBM.