Pilot Curriculum for Continued Professional Development of Radiation Oncology Nurses.

Purpose: Limited structured educational programs are available for the continued professional development of radiation oncology nurses. In this study, we evaluated a pilot curriculum focusing on clinical workflow and toxicity management for radiation oncology nurses at a single university-affiliated medical center network. Methods and Materials: Based on a previous multi-institutional needs assessment, a targeted curriculum on clinical workflow and toxicity management was developed, including didactic lectures, written disease-specific toxicity management guidelines, and standardized medication/laboratory order preference lists in the electronic health record. An anonymized survey was circulated to all participants pre- and postcurriculum. The survey was composed of Likert-type subjective questions and 11 objective knowledge-based questions (KBQs). Paired Likert-type data were analyzed using Wilcoxon signed ranks test. Objective question data were compared with the McNamar's mid P test. Results: Thirteen nurses participated in the pilot curriculum and 100% completed pre- and post curriculum surveys. After the didactics, nurses reported a significant increase in their understanding of the responsibilities of a nurse and overall process of care and their ability to explain computed tomography simulation, as well as their ability to assess, manage, and grade radiation-related toxicities (P < .01). There was significant improvement in the percent of correct answers on objective KBQs from a baseline of 52% to 80% after the curriculum (P < .01). Qualitatively, 70% (9/13) of nurses rated the curriculum as "extremely useful" and 30% (4/13) as "quite useful." Conclusions: Our pilot curriculum using a combination of in-person formal didactics, toxicity management guidelines, and electronic health record based order preference lists was well-received and showed promising results on KBQ assessment. This work may be used to guide the development of larger curricula for nurse onboarding and continuing education in a multicenter setting.

CNS Downstaging: An Emerging Treatment Paradigm for Extensive Brain Metastases in Oncogene-Addicted Lung Cancer.

INTRODUCTION: For extensive brain metastases (BrM) presentations arising from oncogene-addicted lung cancer, tyrosine kinase inhibitors (TKIs) with high response rates in the central nervous system (CNS) could potentially downstage the CNS disease burden, allowing for the avoidance of upfront whole-brain radiotherapy (WBRT) and the conversion of some patients into candidates for focal stereotactic radiosurgery (SRS). METHODS: We describe the outcomes of patients with ALK, EGFR, and ROS1-driven NSCLC with extensive BrM presentations (defined as > 10 BrMs or leptomeningeal disease) treated with upfront newer generation CNS-active TKIs alone, including osimertinib, alectinib, brigatinib, lorlatinib, and entrectinib, from 2012 to 2021 at our institution. All BrMs were contoured at study entry, best CNS response (nadir), and first CNS progression. RESULTS: Twelve patients met criteria including 6 with ALK, 3 with EGFR, and 3 with ROS1-driven NSCLC. The median number and volume of BrMs at presentation were 49 and 19.6 cm3, respectively. Eleven patients (91.7 %) achieved a CNS response by modified-RECIST criteria to upfront TKI (10 partial responses, 1 complete response, 1 stable disease) with nadir observed at a median of 5.1 months. At nadir, the median number and volume of BrMs were 5 (median 91.7 % reduction per-patient) and 0.3 cm3(median 96.5 % reduction per-patient), respectively. Eleven patients (91.6 %) developed subsequent CNS progression (7 local failures, 3 local + distant, 1 distant) at a median of 17.9 months. At CNS progression, the median number and volume of BrMs were 7 and 0.7 cm3, respectively. Seven patients (58.3 %) received salvage SRS and no patients received salvage WBRT. The median overall survival from initiation of TKI for the extensive BrM presentation was 43.2 months. CONCLUSION: In this initial case series, we describe CNS downstaging as a promising multidisciplinary treatment paradigm involving the upfront administration CNS-active systemic therapy and close MRI surveillance for extensive BrMs as a strategy to avoid upfront WBRT and to convert some patients into SRS candidates.

Practical Implementation of Emergent After-Hours Radiation Treatment Process Using Remote Treatment Planning on Optimized Diagnostic CT Scans.

The purpose of this report is to present the implementation of a process for after-hours radiation treatment (RT) utilizing remote treatment planning based on optimized diagnostic computed tomography (CT) scans for the urgent palliative treatment of inpatients. A standardized operating procedure was developed by an interprofessional panel to improve the quality of after-hours RT and minimize the risk of treatment errors. A new diagnostic CT protocol was created that could be performed after-hours on hospital scanners and would ensure a reproducible patient position and adequate field of view. An on-call structure for dosimetry staff was created utilizing remote treatment planning. The optimized CT protocol was developed in collaboration with the radiology department, and a novel order set was created in the electronic health system. The clinical workflow begins with the radiation oncologist notifying the on-call team (therapist, dosimetrist, and physicist) and obtaining an optimized diagnostic CT scan on a hospital-based scanner. The dosimetrist remotely creates a plan; the physicist checks the plan; and the patient is treated. Plans are intentionally simple (parallel opposed fields, symmetric jaws) to expedite care and reduce the risk of error. Education on the new process was provided for all relevant staff. Our process was successfully implemented with the use of an optimized CT protocol and remote treatment planning. This approach has the potential to improve the quality and safety of emergent after-hours RT by better approximating the normal process of care.

Hypofractionated re-irradiation to the brainstem in children with recurrent brain tumors.

To characterize radiation necrosis following hypofractionated brainstem re-irradiation in pediatric patients, we reviewed 23 cases with 28 tumors invading or abutting brainstem and treated with hypofractionated re-irradiation from 2004 to 2014. Re-irradiation delivered total doses of 16-30 Gy in two to five fractions. The most commons regimens used were 24 Gy in three fractions and 25 Gy in five fractions. At median follow-up of 12.8 months, median overall survival was 14.7 months and eight in-field recurrences were detected (median time 10.5 months). Five patients experienced symptomatic brainstem necrosis, and all having received 24 Gy in three fractions. Hypofractionated brainstem re-irradiation may be safer in five fractions.

Association of Adjuvant Chemoradiotherapy vs Radiotherapy Alone With Survival in Patients With Resected Major Salivary Gland Carcinoma: Data From the National Cancer Data Base.

Importance: Data on adjuvant concurrent chemoradiotherapy (CRT) after resection of salivary gland carcinomas (SGCs) are limited. Objective: To examine overall survival (OS) outcomes of patients who receive CRT vs radiotherapy (RT) alone after resection of SGCs. Design, Setting, and Participants: The National Cancer Data Base (NCDB), a hospital-based registry that represents 70% of all cancer cases in the United States, was queried for patients who underwent resection of major SGCs with at least 1 high-risk feature (T3-T4 stage, N1-N3 stage, or positive margins). Included patients had histologic findings for malignant SGC with grades 2 to 3 disease and at least 1 high-risk feature. All patients underwent resection with postoperative CRT or RT alone. Patients were treated from 1998 to 2011. Data were analyzed from January to March 2016. Exposures: Patients received CRT, defined as chemotherapy start within 14 days of RT initiation, or RT alone. Main Outcomes and Measures: Univariate, multivariate, and propensity score-matched analyses were performed to compare OS for patients undergoing CRT vs RT alone. Results: Analyses included 2210 eligible patients (1372 men [62.1%] and 838 women [37.9%]; median age [range], 63 [18-90] years); of these, 1842 (83.3%) received RT alone and 368 (16.7%) received CRT. Median follow-up was 39 (range, 2-188) months. Most of the resected major SGCs occurred at the parotid gland (1852 [83.8%]), followed by the submandibular gland (276 [12.5%]), major gland not otherwise specified (66 [3.0%]), and sublingual gland (16 [0.7%]). Unadjusted 2-year OS was worse with adjuvant CRT vs RT alone (71.3% vs 80.2%), as was 5-year OS (38.5% vs 54.2%) (hazard ratio [HR], 1.51; 95% CI, 1.29-1.76; P < .001). Overall survival was inferior with adjuvant CRT on multivariate analysis (HR, 1.22; 95% CI, 1.03-1.44; P = .02) and propensity score-matched analysis (HR, 1.20; 95% CI, 0.98-1.47; P = .08) compared with RT alone. Subgroup analyses by age, comorbidity score, primary site, histologic type, grade, T stage, N stage, margin status, and chemotherapy (single agent vs multiagent) demonstrated equivalent or shorter OS with the addition of chemotherapy to RT. Conclusions and Relevance: This large analysis compared survival outcomes between postoperative CRT and RT alone in patients undergoing resection of high-risk major SGCs using a nationally representative database. The addition of concurrent chemotherapy to RT in patients with high-risk major SGCs did not offer an advantage in OS.

Survival outcomes of adolescent and adult patients with non-seminomatous testicular germ-cell tumors: A population-based study.

BACKGROUND: In adolescents, approximately 90% of testicular germ cell tumors (T-GCTs) are non-seminomas (NS T-GCTs). Few studies have evaluated the impact of age, specifically in adolescence, on outcomes of NS T-GCTs. OBJECTIVE: The purpose of this study was to review all patients diagnosed with NS T-GCTs in the Surveillance, Epidemiology, and End Results (SEER) database to evaluate the association between age (adolescents vs. adults) and survival outcomes. METHOD: The SEER database was queried for individuals ≥13 years old diagnosed with NS T-GCTs from 1995 to 2012. Patients were categorized into adolescent (13-19 years) and adult (≥20 years) cohorts. A Cox proportional hazards model was used for multivariate analysis (MVA). RESULTS: A total of 13,963 patients (1496 adolescents, 12,467 adults) was included. Median follow-up was 71 months (range 1-215). Five-year overall survival (OS) for adolescent and adult patients was 94% and 92%, respectively (p = 0.007); 5-year cancer-specific survival (CSS) was 95% and 94%, respectively (p = 0.139). Under MVA, adolescent patients had improved OS (HR 0.61; 95% CI 0.50-0.75; p < 0.001) and CSS (HR 0.65; 95% CI 0.51-0.82; p < 0.001), when compared with adults (Table). In a logistic regression analysis adjusting for demographics, adolescent patients were more likely to present with regional or distant metastatic disease (OR 1.16; 95% CI 1.01-1.35; p = 0.039), undergo an orchiectomy (OR 2.44; 95% CI 1.50-4.00; p < 0.001) or tumor excision (OR 2.43; 95% CI 1.57-3.77; p < 0.001), and receive other adjuvant surgery (OR 5.87; 95% CI 2.25-15.30; p < 0.001). CONCLUSIONS: To our knowledge, this is the largest population-based comparative analysis in NS T-GCTs comparing outcomes between these two age groups. Adolescent patients with NS T-GCTs had slightly improved survival compared with adults, despite presenting with more advanced disease. While adolescent patients present at more advanced stage, they achieve excellent survival outcomes possibly at the cost of a greater therapeutic burden.

Survival Outcomes of Dose-Escalated External Beam Radiotherapy versus Combined Brachytherapy for Intermediate and High Risk Prostate Cancer Using the National Cancer Data Base.

PURPOSE: We evaluated survival outcomes between dose-escalated EBRT (external beam radiotherapy) vs EBRT plus brachytherapy for intermediate and high risk prostate cancer using NCDB (National Cancer Data Base). MATERIALS AND METHODS: Patients with cN0M0 prostate cancer treated from 2004 to 2006 were divided into radiotherapy comparison groups, including EBRT alone (75.6 to 81 Gy) and EBRT (40 to 50.4 Gy) plus brachytherapy with EBRT delivered at 1.8 to 2.0 Gy per fraction. Brachytherapy data were limited to yes/no with no information on modality, dose or schedule. Eligible patients were known to have received androgen deprivation therapy. Overall survival was evaluated using multivariate Cox regression and propensity score matched analyses. RESULTS: Of the 20,279 study patients with prostate cancer, including 12,617 at intermediate risk and 7,662 at high risk, 71.3% received EBRT alone and 28.7% received EBRT plus brachytherapy. Median followup was 82 months (range 3 to 120) and median age was 70 years (range 36 to 90). On multivariate analysis compared to EBRT alone (75.6 to 81 Gy) EBRT plus brachytherapy was associated with improved survival (HR 0.75, p <0.001). This significance remained consistent for intermediate and high risk when analyzed separately (HR 0.73 and 0.76, respectively, each p <0.001). However on subset analysis compared to very high dose EBRT alone (79.2 to 81 Gy) in all patients combined EBRT plus brachytherapy was not associated with improved survival (HR 0.91, p = 0.083). CONCLUSION: Compared to EBRT (75.6 to 81 Gy) we observed an association of EBRT plus brachytherapy with a decreased risk of death in men with intermediate and high risk prostate cancer. However this association was no longer significant when EBRT doses of 79.2 to 81 Gy were used.

Association of health insurance with outcomes in adults ages 18 to 64 years with melanoma in the United States.

BACKGROUND: Studies evaluating insurance status and melanoma outcomes are limited. OBJECTIVE: We investigated whether health insurance correlates with more advanced disease, receipt of treatment, and survival in melanoma. METHODS: This was a cross-sectional analysis of 61,650 patients with cutaneous melanoma using the Surveillance, Epidemiology, and End Results database. RESULTS: Under multivariate analysis, patients with either Medicaid insurance (hazard ratio, 1.83; 95% confidence interval [CI], 1.65-2.04; P < .001) or uninsured status (hazard ratio, 1.63; 95% CI, 1.44-1.85; P < .001) were more likely to die of any cause, including melanoma. Uninsured compared with non-Medicaid insured cases more often presented with increasing tumor thickness (odds ratio [OR], 2.19; 95% CI, 1.76-2.73; P < .001) and presence of ulceration (OR, 1.64; 95% CI, 1.40-1.92; P < .001), and less often received treatment (OR, 1.87; 95% CI, 1.60-2.19; P < .001). Compared with non-Medicaid insured, Medicaid cases more often had increasing tumor thickness (OR, 2.36; 95% CI, 1.91-2.91; P < .001), advanced stage (OR, 1.59; 95% CI, 1.37-1.85; P < .001), and presence of ulceration (OR, 1.40; 95% CI, 1.19-1.63; P < .001), and less often received treatment (OR, 1.61; 95% CI, 1.37-1.89; P < .001). LIMITATIONS: This was a retrospective study. CONCLUSION: Patients with melanoma and Medicaid or uninsured status were more likely to present with advanced disease and were less likely to receive treatment, likely contributing to an overall and cause-specific survival detriment. Addressing access to care may help improve these outcomes.

Non-Rhabdomyosarcoma Soft Tissue Sarcomas in Children: A Surveillance, Epidemiology, and End Results Analysis Validating COG Risk Stratifications.

PURPOSE: Non-rhabdomyosarcoma soft tissue sarcomas (NRSTS) are a heterogeneous group of sarcomas that encompass over 35 histologies. With an incidence of ∼500 cases per year in the United States in those <20 years of age, NRSTS are rare and therefore difficult to study in pediatric populations. We used the large Surveillance, Epidemiology, and End Results (SEER) database to validate the prognostic ability of the Children's Oncology Group (COG) risk classification system and to define patient, tumor, and treatment characteristics. METHODS AND MATERIALS: From SEER data from 1988 to 2007, we identified patients ≤18 years of age with NRSTS. Data for age, sex, year of diagnosis, race, registry, histology, grade, primary size, primary site, stage, radiation therapy, and survival outcomes were analyzed. Patients with nonmetastatic grossly resected low-grade tumors of any size or high-grade tumors ≤5 cm were considered low risk. Cases of nonmetastatic tumors that were high grade, >5 cm, or unresectable were considered intermediate risk. Patients with nodal or distant metastases were considered high risk. RESULTS: A total of 941 patients met the review criteria. On univariate analysis, black race, malignant peripheral nerve sheath (MPNST) histology, tumors >5 cm, nonextremity primary, lymph node involvement, radiation therapy, and higher risk group were associated with significantly worse overall survival (OS) and cancer-specific survival (CSS). On multivariate analysis, MPNST histology, chemotherapy-resistant histology, and higher risk group were significantly poor prognostic factors for OS and CSS. Compared to low-risk patients, intermediate patients showed poorer OS (hazard ratio [HR]: 6.08, 95% confidence interval [CI]: 3.53-10.47, P<.001) and CSS (HR: 6.27; 95% CI: 3.44-11.43, P<.001), and high-risk patients had the worst OS (HR: 13.35, 95% CI: 8.18-21.76, P<.001) and CSS (HR: 14.65, 95% CI: 8.49-25.28, P<.001). CONCLUSIONS: The current COG risk group stratification for children with NRSTS has been validated with a large number of children in the SEER database.

Dose painting to treat single-lobe prostate cancer with hypofractionated high-dose radiation using targeted external beam radiation: Is it feasible?

Targeted focal therapy strategies for treating single-lobe prostate cancer are under investigation. In this planning study, we investigate the feasibility of treating a portion of the prostate to full-dose external beam radiation with reduced dose to the opposite lobe, compared with full-dose radiation delivered to the entire gland using hypofractionated radiation. For 10 consecutive patients with low- to intermediate-risk prostate cancer, 2 hypofractionated, single-arc volumetric-modulated arc therapy (VMAT) plans were designed. The first plan (standard hypofractionation regimen [STD]) included the entire prostate gland, treated to 70 Gy delivered in 28 fractions. The second dose painting plan (DP) encompassed the involved lobe treated to 70 Gy delivered in 28 fractions, whereas the opposing, uninvolved lobe received 50.4 Gy in 28 fractions. Mean dose to the opposing neurovascular bundle (NVB) was considerably lower for DP vs STD, with a mean dose of 53.9 vs 72.3 Gy (p < 0.001). Mean penile bulb dose was 18.6 Gy for DP vs 19.2 Gy for STD (p = 0.880). Mean rectal dose was 21.0 Gy for DP vs 22.8 Gy for STD (p = 0.356). Rectum V70 (the volume receiving ≥70 Gy) was 2.01% for DP vs 2.74% for STD (p = 0.328). Bladder V70 was 1.69% for DP vs 2.78% for STD (p = 0.232). Planning target volume (PTV) maximum dose points were 76.5 and 76.3 Gy for DP and STD, respectively (p = 0.760). This study demonstrates the feasibility of using VMAT for partial-lobe prostate radiation in patients with prostate cancer involving 1 lobe. Partial-lobe prostate plans appeared to spare adjacent critical structures including the opposite NVB.

Gleason stratifications prognostic for survival in men receiving definitive external beam radiation therapy for localized prostate cancer.

PURPOSE: Histologic grade analyses for prostate cancer (PCa) have traditionally included Gleason scores (GS) of ≤6, 7, and 8-10. Stratified biochemical progression-free survival has increasingly been reported within these groups on analyses of primary-secondary patterns (PSPs) (e.g., 3+4 vs. 4+3) and overall GS (e.g., 8 vs. 9 vs. 10) but with limited data regarding stratified survival outcomes. In this analysis, outcomes for biopsy-assigned GS 6 to 10 were comprehensively evaluated to identify stratifications prognostic for survival in patients undergoing external beam radiation therapy (EBRT). METHODS: The Surveillance, Epidemiology, and End Results database was examined for T1-4 N0 M0, GS 6 to 10 PCa managed with EBRT alone from 2004 to 2006. GS and PSP variations were analyzed for PCa-specific survival (PCSS) and overall survival (OS). RESULTS: Overall, 26,885 patients were evaluated. Preliminary PSP analyses identified stratifications for 3+4 vs. 4+3 = 7 and 4+4 = 8 vs. GS 8 with pattern 5 (P5) (i.e., 3+5 and 5+3) as significant; however, no differences were observed for 4+5 vs. 5+4 = 9. The primary analysis included stratifications for GS 6, 3+4, 4+3, 4+4, 8 w/P5, 9, and 10, where the 7.5-year PCSS rates were 99%, 97%, 95%, 91%, 86%, 81%, and 78% and 7.5-year OS rates were 83%, 76%, 72%, 67%, 66%, 58%, and 54%, respectively. PCSS differences for sequential score increases were all significant on univariate analyses (all P<0.05). In sequential multivariate analyses of PCSS accounting for age, prostate-specific antigen, T stage, year, marital status, race, and tumor registry, the identified GS stratifications remained significant (all P<0.05), with the exception of GS 8 w/P5 vs. 9 (P = 0.11). In overall multivariate analyses, the identified GS stratifications represented the strongest prognostic factor for survival. Subgroup analyses demonstrated that presence of any P5 was an independent prognostic factor for survival. CONCLUSION: In the largest reported survival analysis of Gleason stratifications, biopsy-assigned GS 6, 3+4, 4+3, 4+4, 8 w/P5, 9, and 10 represented sequential prognostic factors for survival in patients managed with definitive EBRT.

The prognostic significance of Gleason scores in metastatic prostate cancer.

PURPOSE: Although the majority of metastatic prostate cancer (mPCa) will arise from tumors with Gleason scores (GS) of 8 to 10 existing tumor grade analyses for mPCa have been almost uniformly limited to comparisons of ≤7 vs. ≥8. In this analysis, we comprehensively evaluate the GS as a prognostic factor for mPCa in the era of the updated Gleason grading system. METHODS: The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients with mPCa, GS 6 to 10, diagnosed from 2006 to 2008. GS and primary-secondary Gleason pattern variations were analyzed for overall survival and prostate cancer-specific survival (PCSS). RESULTS: A total of 4,654 patients were evaluable. At 4 years, the overall survival rates were 51%, 45%, 34%, 25%, and 15% and PCSS rates were 69%, 57%, 44%, 33%, and 21% for GS 6, 7, 8, 9, and 10, respectively. Survival differences for GS 7 vs. 8, 8 vs. 9, and 9 vs. 10 were highly significant on both univariate and multivariate analyses accounting for age, prostate-specific antigen level, and T stage (all P<0.001). Gleason pattern 5 was an independent prognostic factor, both overall for patients with GS 6 to 10 and on primary-secondary Gleason pattern comparisons within the GS 8 (4+4 vs. 3+5 and 5+3) and GS 9 (4+5 vs. 5+4) subgroups. No survival differences were observed between 3+4 vs. 4+3. Overall, lower prostate-specific antigen level, younger age, and lower GS were associated with improved survival, with GS being the strongest prognostic factor for PCSS. CONCLUSIONS: In this large population-based cohort, stratified survival outcomes were observed for GS 6 to 10, with sequential comparisons of GS 7 to 10, and the presence and extent of Gleason pattern 5 representing independent prognostic factors in the metastatic setting.

The impact of definitive local therapy for lymph node-positive prostate cancer: a population-based study.

PURPOSE: To evaluate the survival outcomes for patients with lymph node-positive, nonmetastatic prostate cancer undergoing definitive local therapy (radical prostatectomy [RP], external beam radiation therapy [EBRT], or both) versus no local therapy (NLT) in the US population in the modern prostate specific antigen (PSA) era. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results database was queried for patients with T1-4N1M0 prostate cancer diagnosed from 1995 through 2005. To allow comparisons of equivalent datasets, patients were analyzed in separate clinical (cN+) and pathologically confirmed (pN+) lymph node-positive cohorts. Kaplan-Meier overall survival (OS) and prostate cancer-specific survival (PCSS) estimates were generated, with accompanying univariate log-rank and multivariate Cox proportional hazards comparisons. RESULTS: A total of 796 cN+ and 2991 pN+ patients were evaluable. Among cN+ patients, 43% underwent EBRT and 57% had NLT. Outcomes for cN+ patients favored EBRT, with 10-year OS rates of 45% versus 29% (P<.001) and PCSS rates of 67% versus 53% (P<.001). Among pN+ patients, 78% underwent local therapy (RP 57%, EBRT 10%, or both 11%) and 22% had NLT. Outcomes for pN+ also favored local therapy, with 10-year OS rates of 65% versus 42% (P<.001) and PCSS rates of 78% versus 56% (P<.001). On multivariate analysis, local therapy in both the cN+ and pN+ cohorts remained independently associated with improved OS and PCSS (all P<.001). Local therapy was associated with favorable hazard ratios across subgroups, including patients aged ≥70 years and those with multiple positive lymph nodes. Among pN+ patients, no significant differences in survival were observed between RP versus EBRT and RP with or without adjuvant EBRT. CONCLUSIONS: In this large, population-based cohort, definitive local therapy was associated with significantly improved survival in patients with lymph node-positive prostate cancer.

The impact of adjuvant radiation therapy for high-grade gliomas by histology in the United States population.

PURPOSE: To compare the survival impact of adjuvant external beam radiation therapy (RT) for malignant gliomas of glioblastoma (GBM), anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and mixed anaplastic oligoastrocytoma (AOA) histology. METHODS AND MATERIALS: The Surveillance, Epidemiology, and End Results (SEER) database was queried from 1998 to 2007 for patients aged ≥18 years with high-grade gliomas managed with upfront surgical resection, treated with and without adjuvant RT. RESULTS: The primary analysis totaled 14,461 patients, with 12,115 cases of GBM (83.8%), 1312 AA (9.1%), 718 AO (4.9%), and 316 AOA (2.2%). On univariate analyses, adjuvant RT was associated with significantly improved overall survival (OS) for GBMs (2-year OS, 17% vs 7%, p<.001), AAs (5-year OS, 38% vs 24%, p<.001), and AOAs (5-year OS, 55% vs 44%, p=.026). No significant differences in OS were observed for AOs (5-year OS, with RT 50% vs 56% without RT, p=.277). In multivariate Cox proportional hazards models accounting for extent of resection, age, sex, race, year, marital status, and tumor registry, RT was associated with significantly improved OS for both GBMs (HR, 0.52; 95% CI, 0.50-0.55; P<.001) and AAs (HR, 0.57; 95% CI, 0.48-0.68; P<.001) but only a trend toward improved OS for AOAs (HR, 0.70; 95% CI, 0.45-1.09; P=.110). Due to the observation of nonproportional hazards, Cox regressions were not performed for AOs. A significant interaction was observed between the survival impact of RT and histology overall (interaction P<.001) and in a model limited to the anaplastic (WHO grade 3) histologies. (interaction P=.024), characterizing histology as a significant predictive factor for the impact of RT. Subgroup analyses demonstrated greater hazard reductions with RT among patients older than median age for both GBMs and AAs (all interaction P≤.001). No significant interactions were observed between RT and extent of resection. Identical patterns of significance were observed for cause-specific survival and OS across analyses. CONCLUSIONS: In this large population-based cohort, glioma histology represented a significant predictor for the survival impact of RT. Adjuvant RT was associated with improved survival for AAs, with benefits comparable to those observed for GBMs over the same 10-year interval. No survival advantage was observed with adjuvant RT for AOs.

In vitro and in vivo enhancement of chemoradiation using the oral PARP inhibitor ABT-888 in colorectal cancer cells.

PURPOSE: Poly(ADP-ribose) polymerase plays a critical role in the recognition and repair of DNA single-strand breaks and double-strand breaks (DSBs). ABT-888 is an orally available inhibitor of this enzyme. This study seeks to evaluate the use of ABT-888 combined with chemotherapy and radiation therapy (RT) in colorectal carcinoma models. METHODS AND MATERIALS: RT clonogenic assays were performed on HCT116 and HT29 cells treated with 5-fluorouracil, irinotecan, or oxaliplatin with or without ABT. The surviving fraction at 2 Gy and dose-modifying factor at 10% survival were analyzed. Synergism was assessed by isobologram analysis for combination therapies. γH2AX and neutral comet assays were performed to assess the effect of therapy on DSB formation/repair. In vivo assessments were made by use of HCT116 cells in a xenograft mouse model. Tumor growth delay was measured at a volume of 500 mm(3). RESULTS: Both lines were radiosensitized by ABT alone, and ABT further increased chemotherapy dose-modifying factors to the 1.6 to 1.8 range. All combinations were synergistic (combination indices <0.9). ABT treatment significantly increased DSB after RT (γH2AX, 69% vs 43%; P=.017) and delayed repair. We found tumor growth delays of 7.22 days for RT; 11.90 days for RT and ABT; 13.5 days for oxaliplatin, RT, and ABT; 14.17 days for 5-fluorouracil, RT, and ABT; and 23.81 days for irinotecan, RT, and ABT. CONCLUSION: ABT-888 radiosensitizes at similar or higher levels compared with classic chemotherapies and acts synergistically with these chemotherapies to enhance RT effects. In vivo confirmation of these results indicates a potential role for combining its use with existing chemoradiation regimens.