Assessing survival in non-small cell lung cancer brain metastases after stereotactic radiosurgery: before and after the start of the targetable mutation era.

PURPOSE: Targeted treatment options for non-small cell lung cancer (NSCLC) brain metastases (BMs) may be combined with stereotactic radiosurgery (SRS) to optimize survival. We assessed patient outcomes after SRS for NSCLC BMs, identifying survival trajectories associated with targetable mutations. METHODS: In this retrospective time-dependent analysis, we analyzed median overall survival of patients who received ≥ 1 SRS courses for BM from NSCLC from 2001 to 2021. We compared survival of patients with and without targetable mutations based on clinical variables and treatment. RESULTS: Among the 213 patients included, 87 (40.8%) had targetable mutations-primarily EGFR (22.5%)-and 126 (59.2%) did not. Patients with targetable mutations were more often female (63.2%, p <.001) and nonsmokers (58.6%, p <.001); had higher initial lung-molGPA (2.0 vs. 1.5, p <.001) and lower cumulative tumor volume (3.7 vs. 10.6 cm3, p <.001); and received more concurrent (55.2% vs. 36.5%, p =.007) and total (median 3 vs. 2, p <.001) systemic therapies. These patients had lower mortality rates (74.7% vs. 91.3%, p <.001) and risk (HR 0.298 [95%CI 0.190-0.469], p <.001) and longer median overall survival (20.2 vs. 7.4 months, p <.001), including survival ≥ 3 years (p =.001). Survival was best predicted by SRS with tumor resection in patients with non-targetable mutations (HR 0.491 [95%CI 0.318-757], p =.001) and by systemic therapy with SRS for those with targetable mutations (HR 0.124 [95%CI 0.013-1.153], p =.067). CONCLUSION: The presence of targetable mutations enhances survival in patients receiving SRS for NSCLC BM, particularly when used with systemic therapies. Survival for patients without targetable mutations was longest with SRS and surgical resection. These results inform best practices for managing patients with NSCLC BM based on driver mutation status.

Gross Tumor and Intracranial Control Benefits with Fractionated Radiotherapy Compared with Stereotactic Radiosurgery for Patients with WHO Grade 2 Meningioma.

OBJECTIVE: Surgical resection is the mainstay of treatment for WHO grade 2 meningioma. Fractionated radiation therapy (RT) is frequently used after surgery, though many centers utilize stereotactic radiosurgery (SRS) for recurrence or progression. Herein, we report disease control outcomes from an institutional cohort with adjuvant fractionated RT versus salvage SRS. METHODS: We identified 32 patients from an institutional database with WHO grade 2 meningioma and residual/recurrent tumor treated with either SRS or fractionated RT. Patients were treated between 2007 and 2021 and had at least 1 year of follow-up. Kaplan-Meier estimators were used to determine gross tumor control (GTC) and intracranial control (IC). Univariate Cox proportional hazards models using biologically effective dose (BED) as a continuous parameter were used to assess for dose responses. RESULTS: With a median follow-up of 5.5 years, 13 patients (41%) received SRS to a recurrent or progressive nodule, 2 (6%) fractionated RT to a recurrent or progressive nodule, and 17 (53%) adjuvant fractionated RT following subtotal resection. Five-year GTC was higher with fractionated RT versus SRS (82% vs. 38%, P = 0.03). Five-year IC was also better with fractionated RT versus SRS (82% vs. 11%, P < 0.001). On univariate analysis, increasing BED10 was significantly associated with better GTC (P = 0.039); increasing BED3 was not (P = 0.82). CONCLUSIONS: In this patient cohort, GTC and IC were significantly higher in patients treated with adjuvant fractionated RT compared with salvage SRS. Increasing BED10 was associated with better GTC. Fractionated RT may provide a better therapeutic ratio than SRS for grade 2 meningiomas.

The importance of considering competing risks in recurrence analysis of intracranial meningioma.

BACKGROUND: The risk of recurrence is overestimated by the Kaplan-Meier method when competing events, such as death without recurrence, are present. Such overestimation can be avoided by using the Aalen-Johansen method, which is a direct extension of Kaplan-Meier that accounts for competing events. Meningiomas commonly occur in older individuals and have slow-growing properties, thereby warranting competing risk analysis. The extent to which competing events are considered in meningioma literature is unknown, and the consequences of using incorrect methodologies in meningioma recurrence risk analysis have not been investigated. METHODS: We surveyed articles indexed on PubMed since 2020 to assess the usage of competing risk analysis in recent meningioma literature. To compare recurrence risk estimates obtained through Kaplan-Meier and Aalen-Johansen methods, we applied our international database comprising ~ 8,000 patients with a primary meningioma collected from 42 institutions. RESULTS: Of 513 articles, 169 were eligible for full-text screening. There were 6,537 eligible cases from our PERNS database. The discrepancy between the results obtained by Kaplan-Meier and Aalen-Johansen was negligible among low-grade lesions and younger individuals. The discrepancy increased substantially in the patient groups associated with higher rates of competing events (older patients with high-grade lesions). CONCLUSION: The importance of considering competing events in recurrence risk analysis is poorly recognized as only 6% of the studies we surveyed employed Aalen-Johansen analyses. Consequently, most of the previous literature has overestimated the risk of recurrence. The overestimation was negligible for studies involving low-grade lesions in younger individuals; however, overestimation might have been substantial for studies on high-grade lesions.

Patterns of failure after radiosurgery for WHO grade 1 or imaging defined meningiomas: Long-term outcomes and implications for management.

BACKGROUND: We analyzed long-term control and patterns of failure in patients with World Health Organization Grade 1 meningiomas treated with definitive or postoperative stereotactic radiosurgery at the authors' affiliated institution. METHODS: 96 patients were treated between 2004 and 2019 with definitive (n = 57) or postoperative (n = 39) stereotactic radiosurgery. Of the postoperative patients, 17 were treated adjuvantly following subtotal resection and 22 were treated as salvage at time of progression. Patients were treated to the gross tumor alone without margin or coverage of the dural tail to a median dose of 15 Gy. Median follow up was 7.4 years (inter-quartile range 4.8-11.3). Local control, marginal control, regional control, and progression-free survival were analyzed. RESULTS: Local control at 5 and 10 years was 97 % and 95 %. PFS at 5 and 10 years was 94 % and 90 % with no failures reported after 6 years. Definitive and postoperative local control were similar at 5 (95 % [82-99 %] vs. 100 %) and 10 years (92 % [82-99 %] vs. 100 %). Patients treated with postoperative SRS did not have an increased marginal failure rate (p = 0.83) and only 2/39 (5 %) experienced recurrence elsewhere in the cavity. CONCLUSIONS: Stereotactic radiosurgery targeting the gross tumor alone provides excellent local control and progression free survival in patients treated definitively and postoperatively. As in the definitive setting, patients treated postoperatively can be treated to gross tumor alone without need for additional margin or dural tail coverage.

Response to high dose ipilimumab plus temozolomide after progression on standard or low dose ipilimumab in advanced melanoma: a retrospective analysis.

Background: Despite advancements in checkpoint inhibitor-based immunotherapy, patients with advanced melanoma who have progressed on standard dose ipilimumab (Ipi) + nivolumab continue to have poor prognosis. Several studies support a dose-response activity of Ipi, and one promising combination is Ipi 10mg/kg (Ipi10) + temozolomide (TMZ). Methods: We performed a retrospective cohort analysis of patients with advanced melanoma treated with Ipi10+TMZ in the immunotherapy refractory/resistant setting (n = 6), using similar patients treated with Ipi3+TMZ (n = 6) as comparison. Molecular profiling by whole exome sequencing (WES) and RNA-seq of tumors harvested through one responder's treatment was performed. Results: With a median follow up of 119 days, patients treated with Ipi10+TMZ had statistically significant longer median progression free survival of 144.5 days (range 27-219) vs 44 (26-75) in Ipi3+TMZ, p=0.04, and a trend for longer median overall survival of 154.5 days (27-537) vs 89.5 (26-548). All patients in the Ipi10 cohort had progressed on prior Ipi+Nivo. WES revealed only 12 shared somatic mutations including BRAF V600E. RNA-seq showed enrichment of inflammatory signatures, including interferon responses in metastatic lesions after standard dose Ipi + nivo and Ipi10 + TMZ compared to the primary tumor, and downregulated negative immune regulators including Wnt and TGFb signaling. Conclusion: Ipi10+TMZ demonstrated efficacy including dramatic responses in patients with advanced melanoma refractory to prior Ipi + anti-PD1, even with CNS metastases. Molecular data suggest a potential threshold of Ipi dose for activation of sufficient anti-tumor immune response, and higher dose Ipi is required for some patients.

NCCN Guidelines® Insights: Central Nervous System Cancers, Version 2.2022.

The NCCN Guidelines for Central Nervous System (CNS) Cancers focus on management of the following adult CNS cancers: glioma (WHO grade 1, WHO grade 2-3 oligodendroglioma [1p19q codeleted, IDH-mutant], WHO grade 2-4 IDH-mutant astrocytoma, WHO grade 4 glioblastoma), intracranial and spinal ependymomas, medulloblastoma, limited and extensive brain metastases, leptomeningeal metastases, non-AIDS-related primary CNS lymphomas, metastatic spine tumors, meningiomas, and primary spinal cord tumors. The information contained in the algorithms and principles of management sections in the NCCN Guidelines for CNS Cancers are designed to help clinicians navigate through the complex management of patients with CNS tumors. Several important principles guide surgical management and treatment with radiotherapy and systemic therapy for adults with brain tumors. The NCCN CNS Cancers Panel meets at least annually to review comments from reviewers within their institutions, examine relevant new data from publications and abstracts, and reevaluate and update their recommendations. These NCCN Guidelines Insights summarize the panel's most recent recommendations regarding molecular profiling of gliomas.

Incidence and extent of disease progression on MRI between surgery and initiation of radiotherapy in glioblastoma patients.

Background: A post-operative MRI (MRIpost-op) performed within 72 h is routinely used for radiation treatment planning in glioblastoma (GBM) patients, with radiotherapy starting about 4-6 weeks after surgery. Some patients undergo an additional pre-radiotherapy MRI (MRIpre-RT) about 2-6 weeks after surgery. We sought to analyze the incidence of rapid early progression (REP) between surgery and initiation of radiotherapy seen on MRIpre-RT and the impact on radiation target volumes. Methods: Patients with GBM diagnosed between 2018 and 2020 who had an MRIpost-op and MRIpre-RT were retrospectively identified. Criteria for REP was based on Modified RANO criteria. Radiation target volumes were created and compared using the MRIpost-op and MRIpre-RT. Results: Fifty patients met inclusion criteria. The median time between MRIpost-op and MRIpre-RT was 26 days. Indications for MRIpre-RT included clinical trial enrollment in 41/50 (82%), new symptoms in 5/50 (10%), and unspecified in 4/50 (8%). REP was identified in 35/50 (70%) of patients; 9/35 (26%) had disease progression outside of the MRIpost-op-based high dose treatment volumes. Treatment planning with MRIpost-op yielded a median undertreatment of 27.1% of enhancing disease and 11.2% of surrounding subclinical disease seen on MRIpre-RT. Patients without REP had a 38% median volume reduction of uninvolved brain if target volumes were planned with MRIpre-RT. Conclusion: Given the incidence of REP and its impact on treatment volumes, we recommend using MRIpre-RT for radiation treatment planning to improve coverage of gross and subclinical disease, allow for early identification of REP, and decrease radiation treatment volumes in patients without REP.

Delineating the Subarachnoid Space in the Adult Lumbosacral Spine Using Computed Tomographic Myelography: An Aid for Clinical Target Volume Delineation in Craniospinal Irradiation.

Purpose: Our aim was to characterize the patterns of cerebrospinal fluid (CSF) extension in the lumbosacral spine using computed tomography (CT) myelograms to provide an evidence base for clinical target volume (CTV) definition in adults receiving craniospinal irradiation. Methods and Materials: This was a retrospective analysis of diagnostic CT lumbar myelograms performed in 30 patients between the ages of 22 and 50. Lateral extension of CSF beyond the thecal sac was measured along each lumbar and sacral nerve root to the nearest millimeter, as was the distance of inferior extension of CSF beyond the caudal end of the thecal sac. Each patient's lateral and inferior CSF extensions were mapped onto a standardized CT data set to create a model target volume in the lumbosacral spine that would contain the aggregate observed CSF distributions from the analyzed CT myelograms. The median extension distances, interquartile ranges, and 90th percentile for distance at each level were calculated. Results: The median lateral extension of CSF along nerve roots beyond the thecal sac-as measured perpendicular to the longitudinal axis-increased from 0 mm (interquartile range [IQR], 0-4 mm) at L1 to 8 mm (IQR, 6-12 mm) at S1 and 0 mm (IQR, 0-0 mm) at S4. The 90th percentile ranged from 5 to 14 mm laterally, with a pattern partially extending into the S1 and S2 sacral foramen. Median CSF extension inferior to the caudal sac was 5 mm (IQR, 2-8 mm), with 90% of patients within 12 mm. An atlas was generated to guide CTV delineation for highly conformal radiation techniques. Conclusion: These results provide information on patterns of CSF extension in the lumbosacral spine of adults and can serve as a model for CTV guidelines that balance comprehensive coverage of the CSF compartment while minimizing the dose to nontarget tissues.

Outcomes using linear accelerator stereotactic radiosurgery for the treatment of trigeminal neuralgia: A single-center, retrospective study.

Background: Linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) treatment of trigeminal neuralgia (TN) may have similar efficacy to Gamma Knife SRS (GK-SRS), but the preponderance of data comes from patients treated with GK-SRS. Our objective was to analyze the outcomes for LINAC-based treatment of TN in patients at our institution. Methods: We retrospectively analyzed data for patients who underwent LINAC-based SRS for TN from 2006 to 2018. Data were collected from the patients' medical records. Nonparametric statistics were used for the analysis. Results: Of the 41 patients treated with LINAC-based SRS (typically 90 Gy dosed using a 4 mm collimator for one fraction) during that time, follow-up data of >3 weeks post-SRS were available for 32 patients. The median pretreatment Barrow Neurological Institute (BNI) pain score was 5 (range 4-5). The follow-up period ranged from 0.9 to 113.2 months (median 5 months). There was significant improvement in postradiation BNI pain score (P < 0.001), with 23 (72%) patients who improved to a BNI pain score of 1-3. One patient had bothersome hypoesthesia postradiation. Approximately 38% of patients who had initial pain control had recurrence of symptoms (BNI > 3). Survival analysis showed a median time to pain recurrence of 30 months. There was no relationship between prior microvascular decompression (MVD) surgery and change in BNI pain score pre- to posttreatment. Conclusion: The results demonstrate that LINAC-based SRS is an effective means to treat TN. Prior MVD surgery did not affect efficacy of SRS in lowering the BNI score from pre- to posttreatment in this patient cohort.

The Clinical Significance of Maximum Tumor Diameter on MRI in Men Undergoing Radical Prostatectomy or Definitive Radiotherapy for Locoregional Prostate Cancer.

INTRODUCTION: Maximum tumor diameter (MTD) on pretreatment magnetic resonance imaging (MRI) has the potential to further risk stratify for men with prostate cancer (PCa) prior to definitive local therapy. We aim to evaluate the prognostic impact of radiographic maximum tumor diameter (MTD) in men with localized prostate cancer. PATIENTS AND METHODS: From a single-center retrospective cohort of men receiving definitive treatment for PCa (radical prostatectomy [RP] or radiotherapy [RT]) with available pretreatment MRI, we conducted univariable and multivariable Cox proportional-hazards models for progression using clinical variables including age, NCCN risk group, radiographic extracapsular extension (ECE), radiographic seminal vesical invasion (SVI), and MTD. RP and RT cohorts were analyzed separately. Covariates were used in a classification and regression tree (CART) analysis and progression-free survival was estimated with the Kaplan-Meier method and groups were compared using log-rank tests. RESULTS: The cohort included 631 patients (n = 428 RP, n = 203 RT). CART analysis identified 4 prognostic groups for patients treated with RP and 2 prognostic groups in those treated with RT. In the RP cohort, NCCN low/intermediate risk group patients with MTD>=15 mm had significantly worse PFS than those with MTD <= 14 mm, and NCCN high-risk patients with radiographic ECE had significantly worse PFS than those without ECE. In the RT cohort, PFS was significantly worse in the cohort with MTD >= 23 mm than those <= 22 mm. CONCLUSION: Radiographic MTD may be a useful prognostic factor for patients with locoregional prostate cancer. This is the first study to illustrate that the importance of pretreatment tumor size may vary based on treatment modality.

Radiation Therapy in Conjunction With Surgical Stabilization of Impending or Pathologic Fractures Secondary to Metastasis: Is There a Difference Between Single and Multifraction Regimens?

PURPOSE: Patients who undergo surgical stabilization for impending or pathologic fractures secondary to metastasis are often treated with radiation therapy to the involved site. We sought to retrospectively analyze outcomes from single versus multifraction regimens of radiation therapy in this setting. METHODS AND MATERIALS: From our institutional radiation database, we identified 87 patients between 2004 and 2016 who had an impending or pathologic fracture from metastatic disease and who underwent surgical fixation in conjunction with either neoadjuvant (within 5 weeks before surgery) or adjuvant (within 10 weeks after surgery) radiation therapy, representing 99 total treatment sites. Patients were included on the basis of intention to treat with bimodality therapy. Baseline patient characteristics were compared using 2-sided t tests and Fisher's exact tests. Cumulative incidence of local failure, reirradiation, and reoperation were calculated using the Fine-Gray method for competing risks. Freedom from complication was calculated using the Kaplan-Meier method. RESULTS: Baseline characteristics between the single (n = 52) and multifraction (n = 47) cohorts were similar with the exception of higher rates of synchronous bony metastasis (83% vs 60%, P = .01) and female patients (71% vs 43%, P = .004) in the single fraction cohort. There was no significant difference in overall survival between treatment groups. After a median follow-up of 13 months, there was no significant difference in the single and multifraction cohorts, respectively, in the 1-year cumulative incidence rates of local failure (4% vs 7%, P = .58), reirradiation (5% vs 4%, P = .95), reoperation (4% vs 0%, P = .30), or 1-year freedom from complication (90% vs 95%, P = .40). CONCLUSIONS: This is the first study comparing outcomes between single and multifraction radiation therapy in conjunction with surgical stabilization of an impending or pathologic fracture. We found no difference in outcomes between single and multifraction regimens in this setting. Given these findings, single fraction perioperative radiation therapy may be a viable treatment option in appropriately selected patients pending prospective validation of these findings.

Comparing adjuvant radiation to adjuvant chemoradiation in postsurgical p16+ oropharyngeal carcinoma patients with extranodal extension or positive margins.

BACKGROUND: Adjuvant guidelines in surgically resected p16+ oropharyngeal carcinoma (OPC) with positive surgical margins (PSM) or extranodal extension (ENE) are based on randomized controlled trials predating p16 status. It remains unclear if adjuvant chemotherapy is necessary in p16+ patients with these features. METHODS: The National Cancer Database was used to identify cases of nonmetastatic p16+ OPC diagnosed from 2010 to 2017. Patients treated with surgical resection followed by adjuvant radiation (aRT) or adjuvant chemoradiation (aCRT) were eligible for analysis. RESULTS: A total of 14 071 patients were eligible for analysis. Overall survival (OS) was not statistically different between aRT and aCRT in patients with PSM (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.56-1.28), ENE (HR 0.93, 95% CI 0.69-1.27) or both (HR 0.73, 95% CI 0.41-1.31). CONCLUSIONS: In patients with p16+ OPC with ENE, PSM, or both, adding chemotherapy to aRT was not associated with improved OS.

The Effect of Maximum Tumor Diameter by MRI on Disease Control in Intermediate and High-risk Prostate Cancer Patients Treated With Brachytherapy Boost.

BACKGROUND: Larger maximum tumor diameter (MTD) has been associated with worse prostate cancer (PCa) outcomes. However, the impact of MTD in PCa treated with external beam radiotherapy and brachytherapy boost (EBRT+BB) remains unknown. MATERIALS AND METHODS: Patients with PCa treated with EBRT+BB were identified from an institutional database. Clinical data including MTD, age, androgen deprivation therapy (ADT) use, prostate specific antigen (PSA), International Society of Urologic Pathology (ISUP) group, clinical T-stage, and presence of adverse pathology on imaging were retrospectively collected. Multivariable and univariable cox proportional hazards models for biochemical failure (BF) and distant metastasis (DM) were produced with MTD grouped by receiver operating characteristic (ROC) cut-point. Cumulative hazard functions for BF and DM were compared with log-rank test and stratified by ISUP group. RESULTS: Of 191 patients treated with EBRT+BB, 113 had MTD measurements available. Larger MTD was associated with increased ADT use and seminal vesicle involvement. ROC optimization identified MTD of 24 mm as the optimal cut-point for both BF and DM. MTD was independently associated with both BF (HR 8.61, P = .048, 95% CI 1.02-72.97) and DM (HR 8.55, P = .05, 95% CI 1.00-73.19). In patients with ISUP group 4 to 5 disease, MTD > 24 mm was independently associated with increased risk of DM (HR 10.13, P = .04, 95% CI 1.13-91.12). CONCLUSIONS: This is the first study to evaluate MTD in the setting of EBRT+BB. These results demonstrate that MTD is independently associated with BF and metastasis. This suggests a possible role for MTD in risk assessment models and clinical decision-making for men receiving EBRT+BB.

The use and efficacy of chemotherapy and radiotherapy in children and adults with pilocytic astrocytoma.

PURPOSE: The aim of this study was to understand the use of chemotherapy (CMT) and radiotherapy (RT) in pilocytic astrocytoma (PA) and their impact on overall survival (OS). METHODS: Data from the National Cancer Database (NCDB) for patients with non-metastatic WHO grade I PA from 2004 to 2014 were analyzed. Pearson's chi-squared test and multivariate logistic regression analyses were performed to assess the distribution of demographic, clinical, and treatment factors. Inverse probability of treatment weighting (IPTW) was used to account for differences in baseline characteristics. Kaplan-Meier analyses and doubly-robust estimation with multivariate Cox proportional hazards modeling were used to analyze OS. RESULTS: Of 3865 patients analyzed, 294 received CMT (7.6%), 233 received RT (6.0%), and 42 (1.1%) received both. On multivariate analyses, decreasing extent of surgical resection was associated with receipt of both CMT and RT. Brainstem tumors were associated with RT, optic nerve tumors were associated with CMT. Cerebellar tumors were inversely associated with both CMT and RT. Younger age was associated with receipt of CMT; conversely, older age was associated with receipt of RT. After IPTW, receipt of CMT and/or RT were associated with an OS decrement compared with matched patients treated with surgery alone or observation (HR 3.29, p < 0.01). CONCLUSIONS: This is the largest study to date to examine patterns of care and resultant OS outcomes in PA. We identified patient characteristics associated with receipt of CMT and RT. After propensity score matching, receipt of CMT and/or RT was associated with decreased OS.

Metastasis, Mortality, and Quality of Life for Men With NCCN High and Very High Risk Localized Prostate Cancer After Surgical and/or Combined Modality Radiotherapy.

PURPOSE: To compare metastasis-free survival, overall survival, and patient-reported quality of life (QOL) of men with National Comprehensive Cancer Network high or very high risk prostate cancer after definitive surgery and/or multimodal radiotherapy (RT). PATIENTS AND METHODS: We studied a retrospective cohort study of 586 patients treated between the years 2000 and 2017 receiving radical prostatectomy with or without postoperative RT, external-beam RT (EBRT) with androgen deprivation therapy (ADT), or EBRT plus brachytherapy (Brachy) boost + ADT. Patient-reported QOL for urinary, bowel, sexual, and overall physical and mental functioning was assessed using the American Urological Association symptom scale, the Sexual Health Inventory in Men, the Rectal-Function Assessment Scale, the Expanded Prostate Cancer Index Composite, and the Veterans RAND 12-Item Health Survey. RESULTS: Median follow-up for survival was 5 years. No significant differences between the treatments were observed for overall survival or metastasis-free survival at the P < .05 threshold. The propensity-adjusted 5-year metastasis-free survival estimates for EBRT + ADT, EBRT + Brachy + ADT, and surgery were 74.6%, 94.8%, and 83.1%, respectively. The EBRT + Brachy + ADT and surgery cohorts had significantly worse mean American Urological Association symptom scores at 6 months than the EBRT + ADT cohort, which resolved by 1 year. Surgical patients had better rectal function scores than EBRT + ADT patients at years 1 to 3, but similar function thereafter. Adjuvant or salvage RT resulted in significant declines in various Expanded Prostate Cancer Index Composite urinary, sexual, and bowel domains, and Veterans RAND 12-Item Health Survey physical but not mental domains. CONCLUSION: Men with very and/or high-risk localized prostate cancer are likely to require multimodal therapy. The overall differences in survival and long-term QOL are similar for men choosing surgical versus RT pathways.

Impact of Brachytherapy Boost and Dose-escalated External Beam Radiotherapy in Margin Positive Cervical Cancer Treated With Chemotherapy and Radiation.

OBJECTIVES: We examined the impact of brachytherapy boost (BB) and external beam radiotherapy (EBRT) dose-escalation on overall survival (OS) for women with cervical cancer receiving postoperative chemotherapy and radiation (CRT) for a positive margin following hysterectomy. MATERIALS AND METHODS: The National Cancer Database (NCDB) was queried from 2004 to 2015 for women with nonmetastatic squamous cell carcinoma or adenocarcinoma of the cervix who had a positive margin following hysterectomy and received postoperative CRT. Patient and treatment characteristics were assessed with multivariate logistic regression. Survival analyses were performed with univariate Cox regression and Kaplan-Meier analyses. Propensity-score weighted cohorts were generated with inverse probability of treatment weighting via generalized boosted regression modeling. RESULTS: Of 630 women receiving CRT, 331 (53%) received EBRT alone and 299 (47%) received EBRT+BB. Eighty-two percent had chemotherapy initiation within 2 weeks of radiation, suggesting concurrent delivery. Median EBRT dose was 5040 cGy. Intracavitary high-dose rate was the most common BB (67%). Inclusion of BB was more likely with larger tumor sizes (odds ratio=1.03, P=0.002). Women receiving EBRT+BB had improved OS compared to EBRT alone for both unweighted (hazard ratio [HR], 0.72; P=0.020) and propensity-score weighted cohorts (HR, 0.70; P=0.017), and this finding was consistent across multiple patient subsets. EBRT dose-escalation >5040 cGy was not found to be associated with OS (unweighted HR, 1.38; P=0.065 and weighted HR, 1.16; P=0.450). CONCLUSION: The addition of BB to standard CRT improved OS for women with cervical cancer and a positive margin after hysterectomy. No consistent survival benefit was seen to EBRT dose-escalation beyond 5040 cGy.

Adjuvant radiation for positive margins in adult head and neck sarcomas is associated with improved survival: Analysis of the National Cancer Database.

BACKGROUND: Adult head and neck (H&N) sarcomas are a rare malignancy with limited data delineating the role of postoperative radiotherapy (PORT), particularly for a positive surgical margin. There are no randomized trials supporting the use of PORT, therefore treatment trends vary between institutions. A positive margin predicts recurrence and poor survival outcomes. This study uses the National Cancer Database (NCDB) to investigate whether PORT improves overall survival (OS) in adult H&N sarcomas with a positive margin and how utilization has changed. METHODS: Patients (n = 1142) in the NCDB from 2004-2013 with adult H&N sarcomas who underwent resection and had a positive margin. RESULTS: Factors significantly associated with increased utilization of PORT were: having insurance, salivary gland primary site, high-risk histology, poor differentiation, and a macroscopic positive margin. Treatment with PORT was associated with improved 5-year OS for all patients with a positive margin (57% vs 48%; P = .002), both microscopic (57% vs 49%; P = .010) and macroscopic (57% vs 41%; P = .036). Improved OS was significant after controlling for other known covariates on multivariate analysis (HR: 0.76; [0.64-0.90]; P = .002). Treatment at a community-based facility was an independent predictor for reduced OS (HR: 1.37; [1.15-1.64]; P < .001). The percentage utilization (53%) of PORT for these patients did not change significantly over time. CONCLUSION: PORT provides a significant survival benefit for adult H&N sarcoma patients with either a microscopic or macroscopic positive margin; however, PORT is underutilized. Treatment at academic/research cancer programs was associated with increased utilization of PORT and improved survival outcomes.

Adjuvant radiation for T1-2N1 oral cavity cancer survival outcomes and utilization treatment trends: Analysis of the SEER database.

OBJECTIVE: Evaluate current practice patterns in the use of adjuvant radiation for T1-2N1 OCSCC patients and investigate its efficacy in the population-based setting. MATERIALS AND METHODS: This study extracted patients who were treated surgically for T1N1 and T2N1 OCSCC without adverse nodal features from the SEER database from 2004 to 2013. Patients with distant metastatic disease, unknown surgery or radiation status, or prior malignancies were excluded. Patients were divided into those who underwent surgical resection with and without adjuvant radiation. Disease-specific survival (DSS) and overall survival (OS) were the primary outcomes measured. RESULTS: 746 patients met inclusion criteria and 70% received adjuvant radiation therapy. Treatment with adjuvant radiation therapy was significantly associated with improved 5-year DSS (65% versus 51%; p < 0.001) and OS (54% versus 44%; p = 0.007) for T1N1 tumors. Likewise, improved 5-year DSS (58% versus 38%; p = 0.009) and OS (48% versus 28%; p = 0.004) was shown in T2N1 tumors. Patients with T2N1 tumors wer significantly more likely to receive adjuvant radiation (75% versus 63%; p < 0.001). Those with insurance and high risk primary subsites: buccal, retromolar trigone, and hard palate were more likely to receive adjuvant radiation. The percent utilization of adjuvant radiation remained constant through the study period for T2N1 tumors (72-74%) but significantly decreased for T1N1 (71-55%) (p = 0.047). CONCLUSION: Adjuvant radiation therapy is independently associated with a significant survival benefit for patients with both T1N1 and T2N1 OCSCC. However, this study demonstrates that patients with T1N1 cancer are less likely to receive adjuvant radiation and utilization is decreasing.

Lymph Node Yield in Therapeutic Neck Dissection: Impact of Dissection Levels and Prior Radiotherapy.

OBJECTIVE: Lymph node yield in therapeutic neck dissection is clinically significant and incompletely studied. We quantified node yield based on extent of neck dissection and presence of preoperative radiation. We also evaluated factors affecting incidence of extracapsular spread (ECS). METHODS: Retrospective review of 499 patients undergoing therapeutic neck dissection; 414 patients met inclusion criteria and were divided into 2 groups: neck dissection alone or before radiation (surgery first: 280 patients; 385 dissections) and primary radiation before surgery (radiation first: 134 patients; 157 dissections). Node yield relative to levels dissected and incidence of ECS were examined. RESULTS: Dissection-specific node yield was greater in the surgery first group for dissection of levels I-V (31.1 ± 16.7 vs 24.0 ± 14.7, P < .001) and levels II-V (26.7 ± 14.4 vs 21.1 ± 10.7). Extracapsular spread incidence was 32.1% (98/305) in the surgery first group and 15.4% (23/149) in the radiation first group ( P < .001). CONCLUSION: This study clarifies anticipated node yield based on number of levels dissected and presence of preoperative radiation. Node yield and incidence of ECS are lower in patients undergoing preoperative radiation.