Real-World Use of Hypofractionated Radiotherapy for Primary CNS Tumors in the Elderly, and Implications on Medicare Spending.

BACKGROUND: For elderly patients with high-grade gliomas, 3-week hypofractionated radiotherapy (HFRT) is noninferior to standard long-course radiotherapy (LCRT). We analyzed real-world utilization of HFRT with and without systemic therapy in Medicare beneficiaries treated with RT for primary central nervous system (CNS) tumors using Centers for Medicare & Medicaid Services data. METHODS: Radiation modality, year, age (65-74, 75-84, or ≥85 years), and site of care (freestanding vs hospital-affiliated) were evaluated. Utilization of HFRT (11-20 fractions) versus LCRT (21-30 or 31-40 fractions) and systemic therapy was evaluated by multivariable logistic regression. Medicare spending over the 90-day episode after RT planning initiation was analyzed using multivariable linear regression. RESULTS: From 2015 to 2019, a total of 10,702 RT courses (ie, episodes) were included (28% HFRT; 65% of patients aged 65-74 years). A considerable minority died within 90 days of RT planning initiation (n=1,251; 12%), and 765 (61%) of those received HFRT. HFRT utilization increased (24% in 2015 to 31% in 2019; odds ratio [OR], 1.2 per year; 95% CI, 1.1-1.2) and was associated with older age (≥85 vs 65-74 years; OR, 6.8; 95% CI, 5.5-8.4), death within 90 days of RT planning initiation (OR, 5.0; 95% CI, 4.4-5.8), hospital-affiliated sites (OR, 1.4; 95% CI, 1.3-1.6), conventional external-beam RT (vs intensity-modulated RT; OR, 2.7; 95% CI, 2.3-3.1), and no systemic therapy (OR, 1.2; 95% CI, 1.1-1.3; P<.001 for all). Increasing use of HFRT was concentrated in hospital-affiliated sites (P=.002 for interaction). Most patients (69%) received systemic therapy with no differences by site of care (P=.12). Systemic therapy utilization increased (67% in 2015 to 71% in 2019; OR, 1.1 per year; 95% CI, 1.0-1.1) and was less likely for older patients, patients who died within 90 days of RT planning initiation, those who received conventional external-beam RT, and those who received HFRT. HFRT significantly reduced spending compared with LCRT (adjusted ß for LCRT = +$8,649; 95% CI, $8,544-$8,755), whereas spending modestly increased with systemic therapy (adjusted ß for systemic therapy = +$270; 95% CI, $176-$365). CONCLUSIONS: Although most Medicare beneficiaries received LCRT for primary brain tumors, HFRT utilization increased in hospital-affiliated centers. Despite high-level evidence for elderly patients, discrepancy in HFRT implementation by site of care persists. Further investigation is needed to understand why patients with short survival may still receive LCRT, because this has major quality-of-life and Medicare spending implications.

Brain Metastases in Pancreatic Ductal Adenocarcinoma: Assessment of Molecular Genotype-Phenotype Features-An Entity With an Increasing Incidence?

PURPOSE: To assess clinical characteristics of patients with metastatic pancreas ductal adenocarcinoma (PDAC) and brain metastases (BM), and to assess somatic and germ-line molecular profiles where performed. PATIENTS AND METHODS: Patients with PDAC and BM between January 1990 and January 2016 were identified. Molecular characteristics of somatic and germ-line testing where performed in the subset of patients who had provided informed consent. Somatic alterations were assessed by either MSK-IMPACT testing (>340 key cancer genes) or Sequenom testing (8-gene panel). Overall survival was calculated from date of diagnosis to either date of last follow-up or death. Survival after BM was calculated from date of diagnosis of BM by radiology or pathology to either date of last follow-up or death. RESULTS: From a total of 5824 patients with PDAC identified from January 2000 to January 2016, twenty-five patients (0.4%) had BM. Median age at PDAC diagnosis was 58 years. Median time to the development of BM from initial PDAC diagnosis was 17 months (range, 0-79 months). Median overall survival after BM diagnosis was 1.5 months (range, 1-31 months). Overall survival for patients who had craniotomy (n = 4) was 11 months (range, 1-31 months), with 2 long-term survivors at 21 and 31 months, respectively. Four patients had leptomeningeal disease. Six of 25 patients had germ-line testing, and 3 had BRCA mutations (2 BRCA1 and 1 BRCA2). Somatic profiling identified KRAS mutations in 100% (4 G12D, 2 G12V, and 1 Q61K). CONCLUSION: BM from PDAC is a rare event. We identified a speculative association of germ-line BRCA1/2 alterations with BM in PDAC, which requires corroboration. Survival after BM development is poor; prolonged survival occurred in selected patients via a multidisciplinary approach.

32P brachytherapy conformal source model RIC-100 for high-dose-rate treatment of superficial disease: Monte Carlo calculations, diode measurements, and clinical implementation.

PURPOSE: A novel (32)P brachytherapy source has been in use at our institution intraoperatively for temporary radiation therapy of the spinal dura and other localized tumors. We describe the dosimetry and clinical implementation of the source. METHODS AND MATERIALS: Dosimetric evaluation for the source was done with a complete set of MCNP5 Monte Carlo calculations preceding clinical implementation. In addition, the depth dose curve and dose rate were measured by use of an electron field diode to verify the Monte Carlo calculations. Calibration procedures using the diode in a custom-designed phantom to provide an absolute dose calibration and to check dose uniformity across the source area for each source before treatment were established. RESULTS: Good agreement was established between the Monte Carlo calculations and diode measurements. Quality assurance measurements results are provided for about 100 sources used to date. Clinical source calibrations were usually within 10% of manufacturer specifications. Procedures for safe handling of the source are described. DISCUSSION: Clinical considerations for using the source are discussed.

Assessment of radiation safety instructions to patients based on measured dose rates following prostate brachytherapy.

PURPOSE: To validate radiation safety instructions to patients and to evaluate the potential radiation doses to members of the public after (125)I or (103)Pd prostate implantation. METHODS AND MATERIALS: Radiation dose rate measurements were made in the immediate postoperative period on 636 consecutive patients with stage T1-T2 prostate cancer who underwent transperineal (125)I or (103)Pd implantation at Memorial Sloan-Kettering Cancer Center during the period from August 1995 through January 2003. RESULTS: The mean radiation dose rate at the anterior skin surface following a prostate implant was 37 microSv/hr for (125)I and 8 microSv/hr for (103)Pd. At 30 cm from the anterior skin surface, these dose rates were reduced to 6 microSv/hr for (125)I and 3 microSv/hr for (103)Pd. At 1 m from the anterior skin surface the dose rates from both types of implants were reduced to less than 1 microSv/hr. The effect of body weight on dose rates from (125)I sources was examined for a select sub-group of patients and the measured dose rate was found to decrease with increasing body weight. In another group of patients, dose rate measurements were made on both lateral skin surfaces and were less than 16.8 microSv/hr in all cases. Assuming a 33% occupancy factor and utilizing the mean measured dose rate for (125)I, the time required to reach an effective dose equivalent limit of 5 mSv for caregivers was estimated to be 19 days on contact with the skin surface. Using a similar calculation, the lifetime doses for (125)I at a distance of 30 cm from the anterior skin surface, as well as the lifetime doses for (103)Pd on contact with the skin surface and at 30 cm from the anterior skin surface can be shown to be less than 5 mSv. CONCLUSIONS: The large number of cases available for this study permits a validation of radiation safety recommendations and provides concrete information from which the permitted exposure times following implantation can be estimated. The data support the conclusion that patients treated with these implants do not represent a radiation risk to members of the public.