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.

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.

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.

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.

The evolving role of adjuvant radiotherapy for elderly women with early-stage breast cancer.

BACKGROUND: Elderly patients with early-stage breast cancer (ESBC) derive a local control benefit from radiotherapy (RT) after lumpectomy, without any apparent effect on overall survival. Therefore, the use of RT is controversial. In the current study, the authors characterized updated trends in RT for elderly patients with estrogen receptor (ER)-positive ESBC. METHODS: Patients aged ≥70 years with ER-positive ESBC measuring ≤2 cm after lumpectomy with negative resection margins and known RT details were identified in the National Cancer Data Base. Patients were classified by year of diagnosis and segregated into 3 groups relative to the initial publication and updated presentation of the Cancer and Leukemia Group B (CALGB) 9343 trial. RT use overall, prescription of hypofractionated RT, and use of boost RT were compared between groups using logistic regression analysis, and the influence of clinicopathologic covariates was determined with multivariable logistic regression analysis. RESULTS: A total of 122,796 elderly patients with ER-positive ESBC who were diagnosed between 1998 and 2011 were identified. Overall, 84,649 patients (68.9%) received adjuvant RT, with a decline observed between successive cohorts (71.3% in the pre-initial publication cohort, 69.5% in the pre-update cohort, and 64.7% in the post-update cohort; P <.001). Hypofractionated RT use increased among treated patients over time (P<.001). Boost RT was used in 67.5% of patients, with a decline noted between the pre-update and post-update cohorts (68.7% vs 57.7%; P<.001). Overall RT use as well as use of boost RT were found to be lower among older patients and those with lower-grade or smaller tumors (P<.001), whereas hypofractionated RT was used more commonly in these groups (P<.001). CONCLUSIONS: RT use appears to have declined in elderly patients with ER-positive ESBC, a finding that is reflective of evidence-based practice integrating mature trial data. Further research is needed to develop tools to aid in the decision-making process regarding the delivery or avoidance of RT in this setting.

Additive Value of MR Simulation Prior to Chemoradiation in Evaluating Treatment Response and Pseudoprogression in High-Grade Gliomas.

BACKGROUND: A dedicated MRI Simulation(MRsim) for radiation treatment(RT) planning in high-grade glioma(HGG) patients can detect early radiological changes, including tumor progression after surgery and before standard of care chemoradiation. This study aimed to determine the impact of using post-op MRI vs. MRsim as the baseline for response assessment and reporting pseudo-progression on follow-up imaging at one month(FU1) after chemoradiation. METHODS: Histologically confirmed HGG patients were planned for six weeks of RT in a prospective study for adaptive RT planning. All patients underwent post-op MRI, MRsim, and follow-up MRI scans every 2-3 months. Tumor response was assessed by three independent blinded reviewers using Response Assessment in Neuro-Oncology(RANO) criteria when baseline was either post-op MRI or MRsim. Interobserver agreement was calculated using light's kappa. RESULTS: 30 patients (median age 60.5 years; IQR 54.5-66.3) were included. Median interval between surgery and RT was 34 days (IQR 27-41). Response assessment at FU1 differed in 17 patients (57%) when the baseline was post-op MRI vs. MRsim, including true progression vs. partial response(PR) or stable disease(SD) in 11 (37%) and SD vs. PR in 6 (20%) patients. True progression was reported in 19 patients (63.3%) on FU1 when the baseline was post-op MRI vs 8 patients (26.7%) when the baseline was MRsim (p=.004). Pseudo-progression was observed at FU1 in 12 (40%) vs. 4 (13%) patients, when the baseline was post-op MRI vs. MRsim (p=.019). Interobserver agreement between observers was moderate (κ = 0.579; p<0.001). CONCLUSIONS: Our study demonstrates the value of acquiring an updated MR closer to RT in patients with HGG to improve response assessment, and accuracy in evaluation of pseudo-progression even at the early time point of first follow-up after RT. Earlier identification of patients with true progression would enable more timely salvage treatments including potential clinical trial enrolment to improve patient outcomes.

Stereotactic radiosurgery for prostate cancer spine metastases: local control and fracture risk using a simultaneous integrated boost approach.

OBJECTIVE: Variation exists in approaches to delivery of spine stereotactic radiosurgery (SSRS). Here, the authors describe outcomes following single-fraction SSRS performed using a simultaneous integrated boost for the treatment of prostate cancer spine metastases. METHODS: Health records of patients with prostate cancer spine metastases treated with single-fraction SSRS at the authors' institution were reviewed. Treatment was uniform, with 16 Gy to the clinical tumor volume and 18 Gy to the gross tumor volume. The primary endpoint was local recurrence, with secondary endpoints including vertebral fracture and overall survival. Univariate and multivariate competing risk regression models made using the Fine and Gray method were used to identify factors predictive of local recurrence, considering death to be a competing event for local recurrence. RESULTS: A total of 87 targets involving 108 vertebrae in 68 patients were included, with a median follow-up of 22.5 months per treated target. The 1-, 2-, and 4-year cumulative incidence rates of local failure for all targets were 4.6%, 8.4%, and 19%, respectively. The presence of epidural disease (subdistribution hazard ratio [sHR] 5.43, p = 0.04) and SSRS as reirradiation (sHR 16.5, p = 0.02) emerged as significant predictors of local failure in a multivariate model. Hormone sensitivity did not predict local control. Vertebral fracture incidence rates leading to symptoms or requiring intervention at 1, 2, and 4 years were 1.1%, 3.7%, and 8.4%, respectively. In an exploratory analysis of patterns of failure, 3 (25%) failures occurred in the epidural space and only 1 (8%) occurred clearly in the clinical tumor volume. There were several lesions for which the precise location of failure with regard to target volumes was unclear. CONCLUSIONS: High rates of local control were observed, particularly for radiotherapy-naïve lesions without epidural disease. Hormone sensitivity was not predictive of local control in this cohort and fracture risk was low. Further research is needed to better predict which patients are at high risk of recurrence and who might benefit from treatment escalation.

Hypofractionated radiotherapy for glioblastoma: A large institutional retrospective assessment of 2 approaches.

Background: Glioblastoma (GBM) poses therapeutic challenges due to its aggressive nature, particularly for patients with poor functional status and/or advanced disease. Hypofractionated radiotherapy (RT) regimens have demonstrated comparable disease outcomes for this population while allowing treatment to be completed more quickly. Here, we report our institutional outcomes of patients treated with 2 hypofractionated RT regimens: 40 Gy/15fx (3w-RT) and 50 Gy/20fx (4w-RT). Methods: A single-institution retrospective analysis was conducted of 127 GBM patients who underwent 3w-RT or 4w-RT. Patient characteristics, treatment regimens, and outcomes were analyzed. Univariate and multivariable Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). The impact of chemotherapy and RT schedule was explored through subgroup analyses. Results: Median OS for the entire cohort was 7.7 months. There were no significant differences in PFS or OS between 3w-RT and 4w-RT groups overall. Receipt and timing of temozolomide (TMZ) emerged as the variable most strongly associated with survival, with patients receiving adjuvant-only or concurrent and adjuvant TMZ having significantly improved PFS and OS (P < .001). In a subgroup analysis of patients that did not receive TMZ, patients in the 4w-RT group demonstrated a trend toward improved OS as compared to the 3w-RT group (P = .12). Conclusions: This study demonstrates comparable survival outcomes between 3w-RT and 4w-RT regimens in GBM patients. Receipt and timing of TMZ were strongly associated with survival outcomes. The potential benefit of dose-escalated hypofractionation for patients not receiving chemotherapy warrants further investigation and emphasizes the importance of personalized treatment approaches.

Definitive single fraction spine stereotactic radiosurgery for metastatic sarcoma: Simultaneous integrated boost is associated with high tumor control and low vertebral fracture risk.

INTRODUCTION: Sarcoma spinal metastases (SSM) are particularly difficult to manage given their poor response rates to chemotherapy and inherent radioresistance. We evaluated outcomes in a cohort of patients with SSM uniformly treated using single-fraction simultaneous-integrated-boost (SIB) spine stereotactic radiosurgery (SSRS). MATERIALS AND METHODS: A retrospective review was conducted at a single tertiary institution treated with SSRS for SSM between April 2007-April 2023. 16-24 Gy was delivered to the GTV and 16 Gy uniformly to the CTV. Kaplan-Meier analysis was conducted to assess time to progression of disease (PD) with proportionate hazards modelling used to determine hazard ratios (HR) and respective 95 % confidence intervals (CI). RESULTS: 70 patients with 100 lesions underwent SSRS for SSM. Median follow-up was 19.3 months (IQR 7.7-27.8). Median age was 55 years (IQR42-63). Median GTV and CTVs were 14.5 cm3 (IQR 5-32) and 52.7 cm3 (IQR 29.5-87.5) respectively. Median GTV prescription dose and biologically equivalent dose (BED) [α/ß = 10] was 24 Gy and 81.6 Gy respectively. 85 lesions received 24 Gy to the GTV. 27 % of patients had Bilsky 1b or greater disease. 16 of 100 lesions recurred representing a crude local failure rate of 16 % with a median time to failure of 10.4 months (IQR 5.7-18) in cases which failed locally. 1-year actuarial local control (LC) was 89 %. Median overall survival (OS) was 15.3 months (IQR 7.7-25) from SSRS. Every 1 Gy increase in GTV absolute minimum dose (DMin) across the range (5.8-25 Gy) was associated with a reduced risk of local failure (HR = 0.871 [95 % CI 0.782-0.97], p = 0.009). 9 % of patients developed vertebral compression fractures at a median of 13 months post SSRS (IQR 7-25). CONCLUSION: This study represents one of the most homogenously treated and the largest cohorts of patients with SSM treated with single-fraction SSRS. Despite inherent radioresistance, SSRS confers durable and high rates of local control in SSM without unexpected long-term toxicity rates.

Outcomes and Pattern of Care for Spinal Myxopapillary Ependymoma in the Modern Era-A Population-Based Observational Study.

(1) Background: Myxopapillary ependymoma (MPE) is a rare tumor of the spine, typically slow-growing and low-grade. Optimal management strategies remain unclear due to limited evidence given the low incidence of the disease. (2) Methods: We analyzed data from 1197 patients with spinal MPE from the Surveillance, Epidemiology, and End Results (SEER) database (2000-2020). Patient demographics, treatment modalities, and survival outcomes were examined using statistical analyses. (3) Results: Most patients were White (89.9%) with a median age at diagnosis of 42 years. Surgical resection was performed in 95% of cases. The estimated 10-year overall survival was 91.4%. Younger age (hazard ratio (HR) = 1.09, p < 0.001) and receipt of surgery (HR = 0.43, p = 0.007) were associated with improved survival. Surprisingly, male sex was associated with worse survival (HR = 1.86, p = 0.008) and a younger age at diagnosis compared to females. (4) Conclusions: This study, the largest of its kind, underscores the importance of surgical resection in managing spinal MPE. The unexpected association between male sex and worse survival warrants further investigation into potential sex-specific pathophysiological factors influencing prognosis. Despite limitations, our findings contribute valuable insights for guiding clinical management strategies for spinal MPE.

Response of treatment-naive brain metastases to stereotactic radiosurgery.

With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.