An interdisciplinary consensus on the management of brain metastases in patients with renal cell carcinoma.

Brain metastases are a challenging manifestation of renal cell carcinoma. We have a limited understanding of brain metastasis tumor and immune biology, drivers of resistance to systemic treatment, and their overall poor prognosis. Current data support a multimodal treatment strategy with radiation treatment and/or surgery. Nonetheless, the optimal approach for the management of brain metastases from renal cell carcinoma remains unclear. To improve patient care, the authors sought to standardize practical management strategies. They performed an unstructured literature review and elaborated on the current management strategies through an international group of experts from different disciplines assembled via the network of the International Kidney Cancer Coalition. Experts from different disciplines were administered a survey to answer questions related to current challenges and unmet patient needs. On the basis of the integrated approach of literature review and survey study results, the authors built algorithms for the management of single and multiple brain metastases in patients with renal cell carcinoma. The literature review, consensus statements, and algorithms presented in this report can serve as a framework guiding treatment decisions for patients. CA Cancer J Clin. 2022;72:454-489.

Protocol-in-a-Day Workshop: Expediting IRB Approval for Junior and Senior Faculty.

Delays in research protocol development may be a single factor that hinders the career progression of academic faculty. Structured educational guidance during this phase proves crucial in mitigating setbacks in Institutional Review Board (IRB) approval and expediting trial implementation. To address this, the Protocol-in-a-Day (PIAD) workshop, a comprehensive 1-day event involving members from six critical facets of RO clinical trial implementation, was established, offering significant input to individual protocols. Efficacy and satisfaction of the PIAD workshop were assessed through a 5-question survey and the average time from submission to IRB initial approval. The normality of the data was analyzed using the Shapiro-Wilk Test. Nonparametric data was analyzed using a Mann-Whitney U test for significance. A total of 18 protocols that went through the PIAD workshop were activated. The mean time to IRB approval for protocols that went through PIAD was 39.8 days compared to 58.4 days for those that did not go through the PIAD workshop. Based on survey results, 100% of PIAD participants said the PIAD workshop was useful and 94% of participants stated that the PIAD workshop improved the overall quality of their protocol. Participant surveys further highlighted substantial improvements in trial quality, language, and statistical design and revealed that all participants found the workshop helpful. Therefore, both junior and senior faculty benefitted from this educational program during protocol development, as both groups demonstrated shorter times to IRB approval than non-participants. This acceleration not only fosters efficient trial implementation but also supports academic faculty in their career development.

National Cancer Institute Collaborative Workshop on Shaping the Landscape of Brain Metastases Research: challenges and recommended priorities.

Brain metastases are an increasing global public health concern, even as survival rates improve for patients with metastatic disease. Both metastases and the sequelae of their treatment are key determinants of the inter-related priorities of patient survival, function, and quality of life, mandating a multidimensional approach to clinical care and research. At a virtual National Cancer Institute Workshop in September, 2022, key stakeholders convened to define research priorities to address the crucial areas of unmet need for patients with brain metastases to achieve meaningful advances in patient outcomes. This Policy Review outlines existing knowledge gaps, collaborative opportunities, and specific recommendations regarding consensus priorities and future directions in brain metastases research. Achieving major advances in research will require enhanced coordination between the ongoing efforts of individual organisations and consortia. Importantly, the continual and active engagement of patients and patient advocates will be necessary to ensure that the directionality of all efforts reflects what is most meaningful in the context of patient care.

Management of chordoma and chondrosarcoma with definitive dose-escalated single-fraction spine stereotactic radiosurgery.

PURPOSE: The management of chordoma or chondrosarcoma involving the spine is often challenging due to adjacent critical structures and tumor radioresistance. Spine stereotactic radiosurgery (SSRS) has radiobiologic advantages compared with conventional radiotherapy, though there is limited evidence on SSRS in this population. We sought to characterize the long-term local control (LC) of patients treated with SSRS. METHODS: We retrospectively reviewed patients with chordoma or chondrosarcoma treated with dose-escalated SSRS, defined as 24 Gy in 1 fraction to the gross tumor volume. Overall survival (OS) was calculated by Kaplan-Meier functions. Competing risk analysis using the cause-specific hazard function estimated LC time. RESULTS: Fifteen patients, including 12 with chordoma and 3 with chondrosarcoma, with 22 lesions were included. SSRS intent was definitive, single-modality in 95% of cases (N = 21) and post-operative in 1 case (5%). After a median censored follow-up time of 5 years (IQR 4 to 8 years), median LC time was not reached (IQR 8 years to not reached), with LC rates of 100%, 100%, and 90% at 1 year, 2 years, and 5 years. The median OS was 8 years (IQR 3 years to not reached). Late grade 3 toxicity occurred after 23% of treatments (N = 5, fracture), all of which were managed successfully with stabilization. CONCLUSION: Definitive dose-escalated SSRS to 24 Gy in 1 fraction appears to be a safe and effective treatment for achieving durable local control in chordoma or chondrosarcoma involving the spine, and may hold particular importance as a low-morbidity alternative to surgery in selected cases.

Definitive radiotherapy for extracranial oligoprogressive metastatic renal cell carcinoma as a strategy to defer systemic therapy escalation.

OBJECTIVE: To study whether delivering definitive radiotherapy (RT) to sites of oligoprogression in metastatic renal cell carcinoma (mRCC) enabled deferral of systemic therapy (ST) changes without compromising disease control or survival. PATIENTS AND METHODS: We identified patients with mRCC who received RT to three or fewer sites of extracranial progressive disease between 2014 and 2019 at a large tertiary cancer centre. Inclusion criteria were: (1) controlled disease for ≥3 months before oligoprogression, (2) all oligoprogression sites treated with a biologically effective dose of ≥100 Gy, and (3) availability of follow-up imaging. Time-to-event end-points were calculated from the start of RT. RESULTS: A total of 72 patients were identified (median follow-up 22 months, 95% confidence interval [CI] 19-32 months), with oligoprogressive lesions in lung/mediastinum (n = 35), spine (n = 30), and non-spine bone (n = 5). The most common systemic therapies before oligoprogression were none (n = 33), tyrosine kinase inhibitor (n = 23), and immunotherapy (n = 13). At 1 year, the local control rate was 96% (95% CI 87-99%); progression-free survival (PFS), 52% (95% CI 40-63%); and overall survival, 91% (95% CI 82-96%). At oligoprogression, ST was escalated (n = 16), maintained (n = 49), or discontinued (n = 7), with corresponding median (95% CI) PFS intervals of 19.7 (8.2-27.2) months, 10.1 (6.9-13.2) months, and 9.8 (2.4-28.9) months, respectively. Of the 49 patients maintained on the same ST at oligoprogression, 21 did not subsequently have ST escalation. CONCLUSION: Patients with oligoprogressive mRCC treated with RT had comparable PFS regardless of ST strategy, suggesting that RT may be a viable approach for delaying ST escalation. Randomised controlled trials comparing treatment of oligoprogression with RT vs ST alone are needed.

Advances in Diagnosis and Treatment for Leptomeningeal Disease in Melanoma.

PURPOSE OF REVIEW: Melanoma has one of the highest incidences of causing leptomeningeal disease (LMD) among solid tumors. LMD patients have very poor prognosis with a dismal survival despite aggressive management. In this article, we review the current approaches in the management of patients with LMD secondary to melanoma, including updates in diagnosis, treatment, up-to-date clinical studies, and future directions. RECENT FINDINGS: Cerebrospinal fluid (CSF) cytology remains the gold standard for diagnosis, and alternatively, MRI based on clinical presentation can be used. Other approaches such as "liquid biopsies" that detect circulating tumor cells and cell-free DNA have the potential to considerably enhance the diagnosis of LMD from melanoma. As for treatment options, several systemic therapies, involving systemic targeted and immunotherapies have evolved that showed to have possible benefit in LMD patients. Intrathecal chemotherapy, cellular therapy, and immunotherapy are currently under evaluation in Phase I/II clinical trials. In addition, new radiation therapy approaches such as proton cranial-spinal irradiation (CSI) are currently under investigation. LMD management still remains challenging. Future studies are critical to elucidate the pathophysiology of LMD in order to develop new urgently needed diagnostic tools and therapies. Clinical trials ought to be expanded to include patients with LMD. Future clinical studies should also integrate tissue interrogation, scientifically designed therapies, and aggressive, early intervention in patients with suspected LMD.

Dosimetric analysis of MR-LINAC treatment plans for salvage spine SBRT re-irradiation.

PURPOSE: We investigated the feasibility of thoracic spine stereotactic body radiotherapy (SBRT) using the Elekta Unity magnetic resonance-guided linear accelerator (MRL) in patients who received prior radiotherapy. We hypothesized that Monaco treatment plans can improve the gross tumor volume minimum dose (GTVmin) with spinal cord preservation and maintain consistent plan quality during daily adaptation. METHODS: Pinnacle clinical plans for 10 patients who underwent thoracic spine SBRT (after prior radiotherapy) were regenerated in the Monaco treatment planning system for the Elekta Unity MRL using 9 and 13 intensity-modulated radiotherapy (IMRT) beams. Monaco adapt-to-position (ATP) and adapt-to-shape (ATS) workflow plans were generated using magnetic resonance imaging with a simulated daily positional setup deviation, and these adaptive plans were compared with Monaco reference plans. Plan quality measures included target coverage, Paddick conformity index, gradient index, homogeneity index, spinal cord D0.01cc , esophagus D0.01cc , lung V10, and skin D0.01cc . RESULTS: GTVmin values from the Monaco 9-beam and 13-beam plans were significantly higher than those from Pinnacle plans (p < 0.01) with similar spinal cord dose. Spinal cord D0.01cc , esophagus D0.01cc , and lung V10 did not statistically differ among the three plans. The electron-return effect did not induce remarkable dose effects around the lungs or skin. While in the ATP workflow, a large increase in GTVmin was observed at the cost of a 10%-50% increase in spinal cord D0.01cc , in the ATS workflow, the spinal cord dose increase was maintained within 3% of the reference plan. CONCLUSION: These findings show that MRL plans for thoracic spine SBRT are safe and feasible, allowing tumor dose escalation with spinal cord preservation and consistent daily plan adaptation using the ATS workflow. Careful plan review of hot spots and lung dose is necessary for safe MRL-based treatment.

Brain stereotactic radiosurgery using MR-guided online adaptive planning for daily setup variation: An end-to-end test.

Online magnetic resonance (MR)-guided radiotherapy is expected to benefit brain stereotactic radiosurgery (SRS) due to superior soft tissue contrast and capability of daily adaptive planning. The purpose of this study was to investigate daily adaptive plan quality with setup variations and to perform an end-to-end test for brain SRS with multiple metastases treated with a 1.5-Tesla MR-Linac (MRL). The RTsafe PseudoPatient Prime brain phantom was used with a delineation insert that includes two predefined structures mimicking gadolinium contrast-enhanced brain lesions. Daily adaptive plans were generated using six preset and six random setup variations. Two adaptive plans per daily MR image were generated using the adapt-to-position (ATP) and adapt-to-shape (ATS) workflows. An adaptive patient plan was generated on a diagnostic MR image with simulated translational and rotational daily setup variation and was compared with the reference plan. All adaptive plans were compared with the reference plan using the target coverage, Paddick conformity index, gradient index (GI), Brain V12 or V20, optimization time and total monitor units. Target doses were measured as an end-to-end test with two ionization chambers inserted into the phantom. With preset translational variations, V12 from the ATS plan was 17% lower than that of the ATP plan. With a larger daily setup variation, GI and V12 of the ATS plan were 10% and 16% lower than those of the ATP plan, respectively. Compared to the ATP plans, the plan quality index of the ATS plans was more consistent with the reference plan, and within 5% in both phantom and patient plans. The differences between the measured and planned target doses were within 1% for both treatment workflows. Treating brain SRS using an MRL is feasible and could achieve satisfactory dosimetric goals. Setup uncertainties could be accounted for using online plan adaptation. The ATS workflow achieved better dosimetric results than the ATP workflow at the cost of longer optimization time.

Comparison of setup accuracy and efficiency between the Klarity system and BodyFIX system for spine stereotactic body radiation therapy.

BACKGROUND: Spine stereotactic body radiation therapy (SBRT) uses highly conformal dose distributions and sharp dose gradients to cover targets in proximity to the spinal cord or cauda equina, which requires precise patient positioning and immobilization to deliver safe treatments. AIMS: Given some limitations with the BodyFIX system in our practice, we sought to evaluate the accuracy and efficiency of the Klarity SBRT patient immobilization system in comparison to the BodyFIX system. METHODS: Twenty-three patients with 26 metastatic spinal lesions (78 fractions) were enrolled in this prospective observational study with one of two systems - BodyFIX (n = 11) or Klarity (n = 12). All patients were initially set up to external marks and positioned to match bony anatomy on ExacTrac images. Table corrections given by ExacTrac during setup and intrafractional monitoring and deviations from pre- and posttreatment CBCT images were analyzed. RESULTS: For initial setup accuracy, the Klarity system showed larger differences between initial skin mark alignment and the first bony alignment on ExacTrac than BodyFIX, especially in the vertical (mean [SD] of 5.7 mm [4.1 mm] for Klarity vs. 1.9 mm [1.7 mm] for BodyFIX, p-value < 0.01) and lateral (5.4 mm [5.1 mm] for Klarity vs. 3.2 mm [3.2 mm] for BodyFIX, p-value 0.02) directions. For set-up stability, no significant differences (all p-values > 0.05) were observed in the maximum magnitude of positional deviations between the two systems. For setup efficiency, Klarity system achieved desired bony alignment with similar number of setup images and similar setup time (14.4 min vs. 15.8 min, p-value = 0.41). For geometric uncertainty, systematic and random errors were found to be slightly less with Klarity than with BodyFIX based on an analytical calculation. CONCLUSION: With image-guided correction of initial alignment by external marks, the Klarity system can provide accurate and efficient patient immobilization. It can be a promising alternative to the BodyFIX system for spine SBRT while providing potential workflow benefits depending on one's practice environment.

Observed-to-expected incidence ratios of second malignant neoplasms after radiation therapy for medulloblastoma: A Surveillance, Epidemiology, and End Results analysis.

BACKGROUND: The authors analyzed the incidence and types of second malignant neoplasms (SMNs) in patients treated for medulloblastoma. METHODS: The authors compared the incidence of SMNs after radiotherapy (RT) for medulloblastoma in patients treated in 1973-2014 with the incidence in the general population with the multiple primary-standardized incidence ratio function of Surveillance, Epidemiology, and End Results 9. Observed-to-expected incidence (O/E) ratios and 95% confidence intervals (CIs) were reported for the entire cohort and by disease site according to age at diagnosis, treatment era, and receipt of chemotherapy. P values < .05 were considered statistically significant. RESULTS: Of the 1294 patients with medulloblastoma who received RT, 68 developed 75 SMNs. The O/E ratio for SMNs among all patients was 4.49 (95% CI, 3.53-5.62; P < .05). The site at highest risk was the central nervous system (CNS; O/E, 40.62; 95% CI, 25.46-61.51), which was followed by the endocrine system (O/E, 15.95; 95% CI, 9.12-25.91), bone (O/E, 14.45; 95% CI, 1.75-52.21), soft tissues (O/E, 9.01; 95% CI, 1.09-32.56), the digestive system (O/E, 5.03; 95% CI, 2.51-9.00), and the lymphatic/hematopoietic system (O/E, 3.37; 95% CI, 1.35-6.94). The O/E ratio was higher for patients given chemotherapy and RT (O/E, 5.52; 95% CI, 3.75-7.83) than for those given RT only (O/E, 3.96; 95% CI, 2.88-5.32). CONCLUSIONS: Patients with medulloblastoma are at elevated risk for SMNs in comparison with the general population. Variations in O/E for SMNs by organ systems were found for treatment modality, age at diagnosis, and time of diagnosis. The most common site, the CNS, was involved more often in younger patients and those given chemotherapy with RT.

Patterns of care for pediatric patients with newly-diagnosed grade II gliomas.

PURPOSE: We describe large-scale demographic, initial treatment, and outcomes data for pediatric grade II gliomas included in the National Cancer Database from 2004 to 2014. METHODS: Our cohort included cases less than 21 years of age with pathology-confirmed disease. Logistic regressions were used to evaluate the use of chemotherapy (CT) and radiation therapy (RT). Overall survival (OS) rates were determined using Kaplan-Meier estimates and the log-rank test. RESULTS: We identified 803 cases with astrocytoma (56.2%), oligodendroglioma (26.0%), and mixed glioma/glioma NOS (17.8%) histologies. Most cases underwent surgical resection (n = 661). Whereas cases 16 to 21 years of age were more likely than cases 0 to 5 years to receive RT (OR = 7.38, 95% CI 3.58-15.21, p < 0.001), they were less likely to receive CT (OR = 0.34, 95% CI 0.22-0.52, p < 0.001). The 5-year OS rates for all cases, cases that underwent surgical resection, and cases managed with biopsy were 87.5%, 92.7%, and 63.6%, respectively. CONCLUSION: In one of the largest series of pediatric grade II gliomas, astrocytoma was the most common histology. Patterns of care and OS outcomes were similar to grade I gliomas, with surgical resection being the most common initial treatment and associated with a favorable rate of OS. Younger patients were more likely to receive post-operative CT and the use of RT increased with age.

Clinical implementation of automated treatment planning for whole-brain radiotherapy.

The purpose of the study was to develop and clinically deploy an automated, deep learning-based approach to treatment planning for whole-brain radiotherapy (WBRT). We collected CT images and radiotherapy treatment plans to automate a beam aperture definition from 520 patients who received WBRT. These patients were split into training (n = 312), cross-validation (n = 104), and test (n = 104) sets which were used to train and evaluate a deep learning model. The DeepLabV3+ architecture was trained to automatically define the beam apertures on lateral-opposed fields using digitally reconstructed radiographs (DRRs). For the beam aperture evaluation, 1st quantitative analysis was completed using a test set before clinical deployment and 2nd quantitative analysis was conducted 90 days after clinical deployment. The mean surface distance and the Hausdorff distances were compared in the anterior-inferior edge between the clinically used and the predicted fields. Clinically used plans and deep-learning generated plans were evaluated by various dose-volume histogram metrics of brain, cribriform plate, and lens. The 1st quantitative analysis showed that the average mean surface distance and Hausdorff distance were 7.1 mm (±3.8 mm) and 11.2 mm (±5.2 mm), respectively, in the anterior-inferior edge of the field. The retrospective dosimetric comparison showed that brain dose coverage (D99%, D95%, D1%) of the automatically generated plans was 29.7, 30.3, and 32.5 Gy, respectively, and the average dose of both lenses was up to 19.0% lower when compared to the clinically used plans. Following the clinical deployment, the 2nd quantitative analysis showed that the average mean surface distance and Hausdorff distance between the predicted and clinically used fields were 2.6 mm (±3.2 mm) and 4.5 mm (±5.6 mm), respectively. In conclusion, the automated patient-specific treatment planning solution for WBRT was implemented in our clinic. The predicted fields appeared consistent with clinically used fields and the predicted plans were dosimetrically comparable.

Overuse of Diagnostic Brain Imaging Among Patients With Stage IA Non-Small Cell Lung Cancer.

BACKGROUND: Among patients diagnosed with stage IA non-small cell lung cancer (NSCLC), the incidence of occult brain metastasis is low, and several professional societies recommend against brain imaging for staging purposes. The goal of this study was to characterize the use of brain imaging among Medicare patients diagnosed with stage IA NSCLC. METHODS: Using data from linked SEER-Medicare claims, we identified patients diagnosed with AJCC 8th edition stage IA NSCLC in 2004 through 2013. Patients were classified as having received brain imaging if they underwent head CT or brain MRI from 1 month before to 3 months after diagnosis. We identified factors associated with receipt of brain imaging using multivariable logistic regression. RESULTS: Among 13,809 patients with stage IA NSCLC, 3,417 (25%) underwent brain imaging at time of diagnosis. The rate of brain imaging increased over time, from 23.5% in 2004 to 28.7% in 2013 (P=.0006). There was significant variation in the use of brain imaging across hospital service areas, with rates ranging from 0% to 64.0%. Factors associated with a greater likelihood of brain imaging included older age (odds ratios [ORs] of 1.16 for 70-74 years, 1.13 for 75-79 years, 1.31 for 80-84 years, and 1.46 for ≥85 years compared with 65-69 years; all P<.05), female sex (OR, 1.09; P<.05), black race (OR 1.23; P<.05), larger tumor size (ORs of 1.23 for 11-20 mm and 1.28 for 21-30 mm tumors vs 1-10 mm tumors; all P<.05), and higher modified Charlson-Deyo comorbidity score (OR, 1.28 for score >1 vs score of 0; P<.05). CONCLUSIONS: Roughly 1 in 4 patients with stage IA NSCLC received brain imaging at the time of diagnosis despite national recommendations against the practice. Although several patient factors are associated with receipt of brain imaging, there is significant geographic variation across the United States. Closer adherence to clinical guidelines is likely to result in more cost-effective care.

Spine stereotactic radiosurgery for metastases from hepatobiliary malignancies: patient selection using PRISM scoring.

OBJECTIVE: Dose escalation via stereotactic radiation therapy techniques has been necessary for hepatobiliary malignancies in the primary and oligometastatic setting, but such dose escalation is challenging for spine metastases due to spinal cord proximity. Here, we investigate the role of spine stereotactic radiosurgery (SSRS) in the management of such metastases. METHODS: We retrospectively reviewed patients treated with SSRS to spinal metastases from hepatobiliary malignancies between 2004 and 2017 at our Institution. We used the Kaplan-Meier method to calculate overall survival (OS) and local control (LC) and Cox regression analysis to identify factors associated with disease-related outcomes. RESULTS: We identified 28 patients treated to 43 spinal metastases with SSRS for either HCC or cholangiocarcinoma. The 1-year LC and OS were 85% and 23%, respectively. The median time to death was 6.2 months, while median time to local failure was not reached. Tumor volume > 60 cc (SHR 6.65, p = 0.03) and Bilsky ≥ 1c (SHR 4.73, p = 0.05) predicted for poorer LC, while BED10 > 81 Gy trended towards better local control (SHR 4.35, p = 0.08). Child-Pugh Class (HR 3.02, p = 0.003), higher PRISM Group (HR 3.49, p = 0.001), and systemic disease progression (HR 3.65, p = 0.001) were associated with worse mortality based on univariate modeling in patients treated with SSRS; on multivariate analysis, PRISM Group (HR 2.28, p = 0.03) and systemic disease progression (HR 2.67, p = 0.03) remained significant. Four patients (10%) developed compression deformity and one patient (2%) developed radiation neuritis. CONCLUSION: SSRS provides durable local control in patients with metastatic hepatobiliary malignancies, with higher BED necessary to ensure excellent LC. PRISM scoring is a promising prognostic tool to aid SSRS patient selection.

Relationship between treatment center case volume and survival for localized Ewing sarcoma: The role of radiotherapy timing.

In the treatment of localized Ewing sarcoma (EWS), delays in local therapy are known to adversely impact overall survival (OS). However, the role of treatment center volume in EWS outcomes, and the interaction between center volume and local therapy timing with definitive radiotherapy, remains unknown. Using the National Cancer Database, we demonstrate that treatment at the lowest EWS volume centers is associated with reduced OS, explained partly by higher rates of delayed local therapy. Treatment at the highest volume centers results in improved OS, but appears independent of radiotherapy timing. Future efforts to improve care for EWS patients across treatment centers are imperative.

Development of second primary tumors and outcomes in medulloblastoma by treatment modality: A Surveillance, Epidemiology, and End Results analysis.

BACKGROUND: As treatment modalities for medulloblastoma have developed and overall survival (OS) has improved, there are relatively limited data on the impact of long-term effects such as risk of second primary tumors (SPT). To address the knowledge gap, we analyzed factors associated with the risk of SPT and OS by treatment modality for medulloblastoma. METHODS: We queried the Surveillance, Epidemiology, and End Results (SEER)-18 database for patients diagnosed with medulloblastoma in 1973-2014. Patients were then grouped by age, gender, race, geographic region, histology, adjuvant treatment (no radiation [RT] and no chemotherapy [CT], RT and CT, RT alone, or CT alone), era of diagnosis (1973-1994 or 1995-2014), and survival time. Cumulative incidence, factors associated with SPT and OS were analyzed. RESULTS: Of 2271 patients, 146 developed SPT, of which 42 were benign. The incidence of SPT was 3.1% and 4.9% at 10 and 15 years, respectively. The incidence of SPT was 3.1% with RT + CT versus 3.7% with RT alone at 10 years. The most common site for an SPT was the central nervous system. Female gender (P = 0.01) and longer OS of ≥21 years (P < 0.01) were associated with higher risk of SPT. RT + CT led to better OS than RT only (66.1% and 61.4% vs 55.6% and 49.7% at 10 and 15 years) (P < 0.01). CONCLUSIONS: Medulloblastoma patients have a relatively low risk of SPT at 10 years with treatment. Use of RT + CT led to better OS with no statistical difference in SPT compared with the RT alone.

Fractionated stereotactic radiotherapy for local control of resected brain metastases.

PURPOSE: Postoperative stereotactic radiosurgery (SRS) has been shown to establish local control in patients with resected brain metastases, yet its efficacy may be limited, particularly for resected lesions with large post-operative resection cavities. We describe the efficacy of postoperative fractionated stereotactic radiotherapy (FSRT) for local control in patients who have undergone resection for brain metastases. METHODS: In this retrospective cohort study, we analyzed patients who received FSRT for resected brain metastases in 3 or 5 fractions. Time to local recurrence was the primary endpoint in this study. RESULTS: Sixty-seven patients (n = 29 female, n = 38 male) met study criteria for review. The median age of the cohort was 62 years (range 18-79 years). Median preoperative tumor volume was 11.1 cm3 (range 0.4-77.0 cm3). The rate of local control was 91.0% at 6 months, 85.1% at 12 months, and 85.1% at 18 months. Estimates of freedom from local recurrence at 6 and 12 months were 90.9% and 84.3%, respectively. Higher biologically equivalent doses (BED10) were found to be predictive of longer freedom from local recurrence on univariate and multivariable analysis. Larger cavity volumes were found to correspond to longer time to local recurrence on univariate and multivariable analysis. CONCLUSION: Our results suggest that postoperative FSRT may be an effective method for providing local control to the surgical bed in patients with resected brain metastases, particularly for larger tumors not amenable to conventional, single-fraction SRS. Additional prospective studies are needed to confirm these findings.

Concurrent chemoradiotherapy versus radiotherapy alone for "biopsy-only" glioblastoma multiforme.

BACKGROUND: Combined temozolomide and radiotherapy (RT) is the standard postoperative therapy for glioblastoma multiforme (GBM). However, the clearest benefit of concurrent chemoradiotherapy (CRT) observed in clinical trials has been among patients who undergo surgical resection. Whether the improved survival with CRT extends to patients who undergo "biopsy only" is less certain. The authors compared overall survival (OS) in a national cohort of patients with GBM who underwent biopsy and received either RT alone or CRT during the temozolomide era. METHODS: The US National Cancer Data Base was used to identify patients with histologically confirmed, biopsy-only GBM who received either RT alone or CRT from 2006 through 2011. Demographic and clinicopathologic predictors of treatment were analyzed using the chi-square test, the t test, and multivariable logistic regression. OS was evaluated using the log-rank test, multivariable Cox proportional hazard regression, and propensity score-matched analysis. RESULTS: In total, 1479 patients with biopsy-only GBM were included, among whom 154 (10.4%) received RT alone and 1325 (89.6%) received CRT. The median age at diagnosis was 61 years. CRT was associated with a significant OS benefit compared with RT alone (median, 9.2 vs 5.6 months; hazard ratio [HR], 0.64; 95% confidence interval [CI], 0.54-0.76; P < .001). CRT was independently associated with improved OS compared with RT alone on multivariable analysis (HR, 0.71; 95% CI, 0.60-0.85; P < .001). A significant OS benefit for CRT persisted in a propensity score-matched analysis (HR, 0.72; 95% CI, 0.56-0.93; P = .009). CONCLUSIONS: The current data suggest that CRT significantly improves OS in patients with GBM who undergo biopsy only compared with RT alone and should remain the standard of care for patients who can tolerate therapy. Cancer 2016;122:2364-2370. © 2016 American Cancer Society.

Addition of radiotherapy to adjuvant chemotherapy is associated with improved overall survival in resected pancreatic adenocarcinoma: An analysis of the National Cancer Data Base.

BACKGROUND: The optimal treatment for resected pancreatic cancer is controversial because direct comparisons of adjuvant chemotherapy (CT) alone and chemotherapy and radiotherapy (CRT) are limited. This study assessed outcomes of CT versus CRT in a national cohort to provide a modern estimate of comparative effectiveness. METHODS: Patients with pT1-3N0-1M0 pancreatic adenocarcinoma after pancreatectomy were identified in the National Cancer Data Base. Overall survival (OS) was compared for CT and CRT groups with Cox regression and propensity score matching. Subset analyses by clinicopathologic characteristics were performed. RESULTS: This study identified 6165 patients treated with CT (n = 2334 or 38%) or CRT (n = 3831 or 62%). Most were classified as pT3 (72%), pN1 (67%), and status-post R0 resection (84%). For CRT patients, the median radiotherapy dose was 50.4 Gy. Compared with CT, CRT was associated with improved OS in a univariate analysis (median, 20.0 vs 22.3 months; at 5 years, 16.5% vs 19.6%; P < .001) and a multivariate analysis (hazard ratio [HR], 0.893; 95% confidence interval [CI], 0.837-0.953; P = .001). CRT remained associated with improved OS after propensity score matching (HR, 0.851; 95% CI, 0.793-0.913; P < .001). Subset analyses showed that CRT was associated with improved OS among patients with pT3 (HR, 0.892; 95% CI, 0.828-0.962; P = .003) or pN1 disease (HR, 0.856; 95% CI, 0.793-0.924; P < .001) and both R0 resection (HR, 0.901; 95% CI, 0.839-0.969; P = .005) and R1 resection (HR, 0.842; 95% CI, 0.722-0.983; P = .030). CONCLUSIONS: CRT was independently associated with improved OS after the resection of pancreatic adenocarcinoma in a large national cohort and particularly among patients with R1 resection and pN1 disease. Well-designed randomized comparisons of CRT and CT are urgently needed.