Bree R. Eaton

Hypofractionated radiosurgery for intact or resected brain metastases: defining the optimal dose and fractionation

BackgroundHypofractionated Radiosurgery (HR) is a therapeutic option for delivering partial brain radiotherapy (RT) to large brain metastases or resection cavities otherwise not amenable to single fraction radiosurgery (SRS). The use, safety and efficacy of HR for brain metastases is not well characterized and the optimal RT dose-fractionation schedule is undefined.MethodsForty-two patients treated with HR in 3-5 fractions for 20 (48%) intact and 22 (52%) resected brain metastases with a median maximum dimension of 3.9 cm (0.8-6.4 cm) between May 2008 and August 2011 were reviewed. Twenty-two patients (52%) had received prior radiation therapy. Local (LC), intracranial progression free survival (PFS) and overall survival (OS) are reported and analyzed for relationship to multiple RT variables through Cox-regression analysis.ResultsThe most common dose-fractionation schedules were 21 Gy in 3 fractions (67%), 24 Gy in 4 fractions (14%) and 30 Gy in 5 fractions (12%). After a median follow-up time of 15 months (range 2-41), local failure occurred in 13 patients (29%) and was a first site of failure in 6 patients (14%). Kaplan-Meier estimates of 1 year LC, intracranial PFS, and OS are: 61% (95% CI 0.53 – 0.70), 55% (95% CI 0.47 – 0.63), and 73% (95% CI 0.65 – 0.79), respectively. Local tumor control was negatively associated with PTV volume (p = 0.007) and was a significant predictor of OS (HR 0.57, 95% CI 0.33 - 0.98, p = 0.04). Symptomatic radiation necrosis occurred in 3 patients (7%).ConclusionsHR is well tolerated in both new and recurrent, previously irradiated intact or resected brain metastases. Local control is negatively associated with PTV volume and a significant predictor of overall survival, suggesting a need for dose escalation when using HR for large intracranial lesions.

Clinical Outcomes Among Children With Standard-Risk Medulloblastoma Treated With Proton and Photon Radiation Therapy: A Comparison of Disease Control and Overall Survival.

PURPOSE The purpose of this study was to compare long-term disease control and overall survival between children treated with proton and photon radiation therapy (RT) for standard-risk medulloblastoma. METHODS AND MATERIALS This multi-institution cohort study includes 88 children treated with chemotherapy and proton (n=45) or photon (n=43) RT between 2000 and 2009. Overall survival (OS), recurrence-free survival (RFS), and patterns of failure were compared between the 2 cohorts. RESULTS Median (range) age was 6 years old at diagnosis (3-21 years) for proton patients versus 8 years (3-19 years) for photon patients (P=.011). Cohorts were similar with respect to sex, histology, extent of surgical resection, craniospinal irradiation (CSI) RT dose, total RT dose, whether the RT boost was delivered to the posterior fossa (PF) or tumor bed (TB), time from surgery to RT start, or total duration of RT. RT consisted of a median (range) CSI dose of 23.4 Gy (18-27 Gy) and a boost of 30.6 Gy (27-37.8 Gy). Median follow-up time is 6.2 years (95% confidence interval [CI]: 5.1-6.6 years) for proton patients versus 7.0 years (95% CI: 5.8-8.9 years) for photon patients. There was no significant difference in RFS or OS between patients treated with proton versus photon RT; 6-year RFS was 78.8% versus 76.5% (P=.948) and 6-year OS was 82.0% versus 87.6%, respectively (P=.285). On multivariate analysis, there was a trend for longer RFS with females (P=.058) and higher CSI dose (P=.096) and for longer OS with females (P=.093). Patterns of failure were similar between the 2 cohorts (P=.908). CONCLUSIONS Disease control with proton and photon radiation therapy appears equivalent for standard risk medulloblastoma.

Institutional Enrollment and Survival among NSCLC Patients Receiving Chemoradiation: NRG Oncology Radiation Therapy Oncology Group (RTOG) 0617

BACKGROUND The purpose of this analysis is to evaluate the effect of institutional accrual volume on clinical outcomes among patients receiving chemoradiation for locally advanced non-small cell lung cancer (LA-NSCLC) on a phase III trial. METHODS Patients with LA-NSCLC were randomly assigned to 60 Gy or 74 Gy radiotherapy (RT) with concurrent carboplatin/paclitaxel +/- cetuximab on NRG Oncology RTOG 0617. Participating institutions were categorized as low-volume centers (LVCs) or high-volume centers (HVCs) according to the number of patients accrued (≤3 vs > 3). All statistical tests were two-sided. RESULTS Range of accrual for LVCs (n = 195) vs HVCs (n = 300) was 1 to 3 vs 4 to 18 patients. Baseline characteristics were similar between the two cohorts. Treatment at a HVC was associated with statistically significantly longer overall survival (OS) and progression-free survival (PFS) compared with treatment at a LVC (median OS = 26.2 vs 19.8 months; HR = 0.70, 95% CI = 0.56 to 0.88, P = .002; median PFS: 11.4 vs 9.7 months, HR = 0.80, 95% CI = 0.65-0.99, P = .04). Patients treated at HVCs were more often treated with intensity-modulated RT (54.0% vs 39.5%, P = .002), had a lower esophageal dose (mean = 26.1 vs 28.0 Gy, P = .03), and had a lower heart dose (median = V5 Gy 38.2% vs 54.1%, P = .006; V50 Gy 3.6% vs 7.3%, P < .001). Grade 5 adverse events (AEs) (5.3% vs 9.2%, P = .09) and RT termination because of AEs (1.3% vs 4.1%, P = .07) were less common among patients treated at HVCs. HVC remained independently associated with longer OS (P = .03) when accounting for other factors. CONCLUSION Treatment at institutions with higher clinical trial accrual volume is associated with longer OS among patients with LA-NSCLC participating in a phase III trial.

Endocrine outcomes with proton and photon radiotherapy for standard risk medulloblastoma

BACKGROUND Endocrine dysfunction is a common sequela of craniospinal irradiation (CSI). Dosimetric data suggest that proton radiotherapy (PRT) may reduce radiation-associated endocrine dysfunction but clinical data are limited. METHODS Seventy-seven children were treated with chemotherapy and proton (n = 40) or photon (n = 37) radiation between 2000 and 2009 with ≥3 years of endocrine screening. The incidence of multiple endocrinopathies among the proton and photon cohorts is compared. Multivariable analysis and propensity score adjusted analysis are performed to estimate the effect of radiotherapy type while adjusting for other variables. RESULTS The median age at diagnosis was 6.2 and 8.3 years for the proton and photon cohorts, respectively (P = .010). Cohorts were similar with respect to gender, histology, CSI dose, and total radiotherapy dose and whether the radiotherapy boost was delivered to the posterior fossa or tumor bed. The median follow-up time was 5.8 years for proton patients and 7.0 years for photon patients (P = .010). PRT was associated with a reduced risk of hypothyroidism (23% vs 69%, P < .001), sex hormone deficiency (3% vs 19%, P = .025), requirement for any endocrine replacement therapy (55% vs 78%, P = .030), and a greater height standard deviation score (mean (± SD) -1.19 (± 1.22) vs -2 (± 1.35), P = .020) on both univariate and multivariate and propensity score adjusted analysis. There was no significant difference in the incidence of growth hormone deficiency (53% vs 57%), adrenal insufficiency (5% vs 8%), or precocious puberty (18% vs 16%). CONCLUSIONS Proton radiotherapy may reduce the risk of some, but not all, radiation-associated late endocrine abnormalities.

Radiation therapy target volume reduction in pediatric rhabdomyosarcoma

The use of radiation therapy (RT) “cone‐down” boost to reduce high‐dose treatment volumes according to tumor response to induction chemotherapy in patients with pediatric rhabdomyosarcoma (RMS) may reduce treatment morbidity, yet the impact on tumor control is unknown.

Quantitative Dosimetry for Yttrium-90 Radionuclide Therapy: Tumor Dose Predicts Fluorodeoxyglucose Positron Emission Tomography Response in Hepatic Metastatic Melanoma

PURPOSE To assess a new method for generating patient-specific volumetric dose calculations and analyze the relationship between tumor dose and positron emission tomography (PET) response after radioembolization of hepatic melanoma metastases. METHODS AND MATERIALS Yttrium-90 ((90)Y) bremsstrahlung single photon emission computed tomography (SPECT)/computed tomography (CT) acquired after (90)Y radioembolization was convolved with published (90)Y Monte Carlo estimated dose deposition kernels to create a three-dimensional dose distribution. Dose-volume histograms were calculated for tumor volumes manually defined from magnetic resonance imaging or PET/CT imaging. Tumor response was assessed by absolute reduction in maximum standardized uptake value (SUV(max)) and total lesion glycolysis (TLG). RESULTS Seven patients with 30 tumors treated with (90)Y for hepatic metastatic melanoma with available (90)Y SPECT/CT and PET/CT before and after treatment were identified for analysis. The median (range) for minimum, mean, and maximum dose per tumor volume was 16.9 Gy (5.7-43.5 Gy), 28.6 Gy (13.8-65.6 Gy) and 36.6 Gy (20-124 Gy), respectively. Response was assessed by fluorodeoxyglucose PET/CT at a median time after treatment of 2.8 months (range, 1.2-7.9 months). Mean tumor dose (P = .03) and the percentage of tumor volume receiving ≥ 50 Gy (P < .01) significantly predicted for decrease in tumor SUV(max), whereas maximum tumor dose predicted for decrease in tumor TLG (P < .01). CONCLUSIONS Volumetric dose calculations showed a statistically significant association with metabolic tumor response. The significant dose-response relationship points to the clinical utility of patient-specific absorbed dose calculations for radionuclide therapy.

Selective internal yttrium-90 radioembolization therapy (90Y-SIRT) versus best supportive care in patients with unresectable metastatic melanoma to the liver refractory to systemic therapy: Safety and efficacy cohort study

Objectives: To investigate survival, efficacy, and safety of selective internal yttrium-90 radioembolization therapy (90Y-SIRT) in patients with unresectable metastatic melanoma (MM) to liver refractory to systemic therapy. Methods: An IRB-approved retrospective review of 58 patients diagnosed with unresectable MM to the liver, refractory to systemic therapy, between February 2003 and March 2012 was conducted. Of these, 28 received resin-based 90Y-SIRT (group A), and 30 patients received best supportive care (group B). Survival was calculated using the Kaplan-Meier method and Cox proportional hazard models. Results: Groups A and B were similar for the Child-Pugh class, ECOG scores, age, sex, and race. Median overall survival (OS) from diagnosis of primary melanoma in groups A and B were 119.9 and 26.1 months, respectively (P<0.001). Median OS from hepatic metastasis in groups A and B were 19.9 and 4.8 months, respectively (P<0.0001). In group A, median OS from hepatic metastasis in the Child-Pugh A, B, and C patients was 37.7, 4.2, and 3.6 months, respectively (P<0.001). In group B, median OS from hepatic metastasis in the Child-Pugh A, B, and C patients was 7.8, 4.2, and 1.9 months, respectively (P=0.04). Within group A, median OS from first 90Y-SIRT was 10.1 months; median OS of the Child-Pugh A, B, and C patients from first 90Y-SIRT was 10.3, 1.2, and 0.9 months, respectively (P=0.04). Median OS from first 90Y-SIRT was significantly greater in the absence of diffuse (>10) liver metastases (15.1 vs. 4.7 mo, P=0.02), and in the absence of extrahepatic metastases (21.3 vs. 8.6 mo, P<0.001). Common clinical toxicities following 90Y-SIRT included abdominal pain (17.9%), fatigue (14.3%), and self-limiting grade III bilirubin toxicity (10.7%). Conclusion: For patients with unresectable MM to the liver refractory to systemic therapy, resin-based 90Y was associated with longer survival from liver metastases than best supportive care. Child-Pugh A patients with <10 metastatic lesions and absence of extrahepatic metastases demonstrated greatest survival following 90Y-SIRT.

The use of proton therapy in the treatment of benign or low-grade pediatric brain tumors.

AbstractRadiation therapy (RT) plays a critical role in the local tumor control of benign and low-grade central nervous system tumors in children but is not without the risk of long-term treatment-related sequelae. Proton therapy (PRT) is an advanced RT modality with a unique dose-deposition pattern that allows for treatment of a target volume with reduced scatter dose delivered to normal tissues compared with conventional photon RT and is now increasingly utilized in children with the hope of mitigating radiation-induced late effects. This article reviews the current literature evaluating the use of PRT in benign and low-grade pediatric central nervous system tumors such as low-grade glioma, craniopharyngioma, and ependymoma. Multiple dosimetric studies support the use of PRT by demonstrating the ability of PRT to better spare critical structures important for cognitive development, endocrine function, and hearing preservation and to reduce the total body dose associated with second malignancy risk. Early clinical data demonstrate that PRT is well tolerated with rates of local tumor control comparable to conventional photon RT series, and long-term clinical data are awaited.

Benefit of adjuvant radiotherapy after breast‐conserving therapy among elderly women with T1‐T2N0 estrogen receptor‐negative breast cancer

The purpose of the current study was to evaluate the impact of radiotherapy (RT) among women aged ≥ 70 years with T1‐2N0 estrogen receptor (ER)‐negative breast cancer using Surveillance, Epidemiology, and End Results (SEER)‐Medicare‐linked data.

Is less more? Comparing chemotherapy alone with chemotherapy and radiation for high-risk grade 2 glioma: An analysis of the National Cancer Data Base: Chemotherapy vs Chemotherapy and Radiation

The addition of chemotherapy to adjuvant radiotherapy (chemotherapy and radiation therapy [CRT]) improves overall survival (OS) for patients with high‐risk grade 2 gliomas; however, the impact of chemotherapy alone (CA) is unknown. This study compares the OS of patients with high‐risk grade 2 gliomas treated with CA versus CRT.