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Valproic acid (VPA) is an anti-epileptic drug with properties of a histone deacetylase inhibitor (HDACi). HDACi play a key role in epigenetic regulation of gene expression and have been increasingly used as anticancer agents. Recent studies suggest that VPA is associated with improved survival in high-grade gliomas. However, effects on lower grade gliomas have not been examined. This study investigates whether use of VPA correlates with tumor grade, histological progression, progression-free and overall survival (OS) in grade II, III, and IV glioma patients. Data from 359 glioma patients (WHO II-IV) treated with temozolomide plus an antiepileptic drug (VPA or another antiepileptic drug) between January 1997 and June 2013 at the Massachusetts General Hospital was analyzed retrospectively. After confounder adjustment, VPA was associated with a 28 % decrease in hazard of death (p = 0.031) and a 28 % decrease in the hazard of progression or death (p = 0.015) in glioblastoma. Additionally, VPA dose correlated with reduced hazard of death by 7 % (p = 0.002) and reduced hazard of progression or death by 5 % (p < 0.001) with each 100 g increase in total dose. Conversely, in grade II and III gliomas VPA was associated with a 118 % increased risk of tumor progression or death (p = 0.014), and every additional 100 g of VPA raised the hazard of progression or death by 4 %, although not statistically significant (p = 0.064). Moreover, grade II and III glioma patients taking VPA had 2.17 times the risk of histological progression (p = 0.020), although this effect was no longer significant after confounder adjustment. In conclusion, VPA was associated with improved survival in glioblastoma in a dose-dependent manner. However, in grade II and III gliomas, VPA was linked to histological progression and decrease in progression-free survival. Prospective evaluation of VPA treatment for glioma patients is warranted to confirm these findings.

PurposeTo demonstrate feasibility and toxicity of linear accelerator–based stereotactic radiation therapy boost (SBRT) for prostate cancer, mimicking a high-dose-rate brachytherapy boost.Methods and MaterialsA phase 1 sequential dose escalation study of SBRT compared 20 Gy, 22 Gy, and 24 Gy to the prostate and 25 Gy, 27.5 Gy, and 30 Gy to the gross tumor volume in 2 fractions, combined with 46 Gy in 23 fractions of external beam radiation. Feasibility of dose escalation (volume receiving 125% and 150% of the dose) while meeting organ-at-risk dose constraints, grade 2 acute and late gastrointestinal and genitourinary toxicity, and freedom from biochemical failure were secondary endpoints.ResultsThirty-six men with intermediate- and high-risk prostate cancer were enrolled with a median follow-up of 24 months. Sixty-four percent of patients had high-risk features. Nine men were enrolled to dose level 1, 6 to level 2, and 6 to level 3. Another 15 patients were treated at dose level 3 on the continuation study. Dose level 3 achieved superior 125% (23.75 Gy) and 150% (28.5 Gy) dose compared to dose levels 1 and 2, with minimal differences in organ-at-risk doses. Kaplan-Meier estimate of freedom from biochemical failure at 3 years was 93.3%. There were no late grade 2 or 3 gastrointestinal events. The late grade 2 genitourinary toxicity at 2 years was 19.3%. Prostate-specific membrane antigen positron emission tomography was performed at 2 years with no local recurrences.ConclusionsWe have shown that a linear accelerator–based SBRT boost for prostate cancer is feasible and can achieve doses comparable to high-dose-rate boost up to the 150% isodose volumes. Rectal, bladder, and urethral doses remained low, and long-term toxicity was the same as or better than previous reports from high-dose-rate or low-dose-rate boost protocols.

IntroductionRadiotherapy outcomes are influenced by treatment delivery geometric accuracy and organ‐at‐risk dose. The location of abdominal structures such as the liver, kidneys and tumour volumes can be strongly influenced by respiratory motion. This increases geometric uncertainty and dose to organs‐at‐risk. One common method of minimising respiratory motion is abdominal compression (AC).MethodsFifteen patients being treated for radiotherapy to upper abdominal tumours were analysed. Each patient underwent 2 four‐dimensional computerised tomography (4D‐CT) scans, one with and one without AC with a pneumatic compression belt. Liver and kidney positions were measured on the 4DCT scans at the peak inspiratory and expiratory respiratory phases. The patient received radiation therapy treatment planned on the CT data set with the technique (compression or no compression) that provided the least respiratory motion.ResultsThere was no statistically significant motion difference over the sample population with AC for the kidneys or liver. Of the 14 evaluable patients, 4, 6 and 6 saw reduction in superior‐inferior motion for left kidney, right kidney and liver respectively. The remainder either had negligible (<2 mm) or increase in motion with AC. For anterior‐posterior motion, 2, 2 and 1 saw a reduction for left‐kidney, right‐kidney and liver respectively.ConclusionAC through the use of a pneumatic compression belt was found to result in inconsistent reduction in kidney and liver respiratory motion. It is recommended that the effect of AC is evaluated on a per‐patient basis.