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Importance: There is a growing debate on the relative benefits of adjuvant chemoradiotherapy (CRT) and boost doses of postoperative radiotherapy (B-PORT) in oropharyngeal squamous cell carcinoma (OPSCC) treated with primary surgery, especially for patients with human papillomavirus (HPV)-driven disease., Objective: To characterize the recent patterns of care in and overall survival (OS) outcomes following the use of adjuvant CRT and B-PORT after primary surgery for OPSCC., Design, Setting, and Participants: Retrospective analysis of patients in the National Cancer Database with stage III to IVA-B OPSCC treated with surgery and adjuvant radiotherapy between 2010 and 2012 at Commission on Cancer-accredited facilities. The data analysis was performed between June 15, 2015, and May 4, 2016., Main Outcomes and Measures: The primary outcomes were prevalence of CRT and B-PORT, and OS. The primary predictors were HPV positivity and high-risk pathologic features (HRPFs) (extracapsular extension and positive surgical margins)., Results: Of the 1409 patients (1153 [82%] male; median age, 57 [interquartile range {IQR}, 51-63] years), 873 (62%) and 789 (56%) patients received CRT and B-PORT, respectively; most patients (n = 583 [79%]) with HRPFs received CRT, and many patients (n = 227 [40%]) without HRPFs received CRT. Multivariable predictors of CRT included adverse pathologic features (extracapsular extension [OR, 6.99; 95% CI, 5.22-9.35], positive surgical margins [OR, 2.07; 95% CI, 1.50-2.87], ≥6 involved nodes [OR, 2.34; 95% CI, 1.39-3.92], or low-neck disease [OR, 1.52; 95% CI, 1.01-2.28]), and treatment at a nonacademic institution (OR, 1.59 [95% CI, 1.21-2.10] for comprehensive community cancer center vs academic program). Patients with HPV-positive disease (OR, 0.47; 95% CI, 0.33-0.68) were less likely to receive CRT; this decrease was limited to absent HRPF treated at academic institutions (n = 173, 44 [25%] received CRT). With a median follow-up of surviving patients of 27 (IQR, 21-33) months, the 2-year OS probability was 92% (95% CI, 90%-94%). Multivariable analysis including age, sex, pathologic T stage, 6 or more positive nodes, and educational status confirmed the prognostic impact of HPV positivity (hazard ratio [HR], 0.41; 95% CI, 0.21-0.80) and HRPFs (positive surgical margins [HR, 2.15; 95% CI, 1.27-3.66] and ≥6 involved nodes [HR, 2.11; 95% CI, 1.13-3.93]), but neither CRT (HR, 1.27; 95% CI, 0.70-2.30) nor B-PORT (HR, 1.04; 95% CI, 0.63-1.73) was associated with improved OS., Conclusions and Relevance: Postoperative CRT and B-PORT following resection of OPSCC were dependent on factors beyond HRPFs, including HPV status and treatment at an academic institution. No benefit was seen with intensified adjuvant therapy, supporting enrollment of the HPV-positive population into deintensification trials.

Background: There has been increased reporting of atypical meningioma (grade II) since the World Health Organization reclassification in 2000, and the use of postoperative radiation therapy (RT) in the treatment of these tumors is controversial. We evaluated patients treated at our institution to identify patient subgroups with increased risk of recurrence that may benefit from adjuvant RT., Methods and Materials: We retrospectively assessed 50 patients treated for World Health Organization grade II meningiomas between March 2000 and February 2013. Sex, race, age of diagnosis, tumor location, performance status, size of tumor, MIB-1 index, resection status, and RT were recorded. Patient follow-up, recurrence, and vital status were measured to assess 3-year overall survival (OS) and recurrence free survival (RFS)., Results: The median follow-up was 37 months (range, 1-148). Female sex was associated with decreased RFS compared with male sex (86.1% vs 100%, P = .047). Subtotal resection demonstrated both inferior RFS (67.5% vs 96.6%, P = .025) and OS compared with gross total resection (70.0% vs 100%, P < .001). Tumors >4.5 cm had worse RFS than tumors ≤4.5 cm (85.4% vs 100%, P = .025). Patient OS was lower in tumors with an MIB-1 index >5% than ≤5% (89.7% vs 100%, P = .008). Eastern Cooperative Oncology Group 2-4 negatively impacted OS relative to patients with an Eastern Cooperative Oncology Group 0-1 (66.7% vs 100%, P < .001)., Conclusions: Significantly higher rates of recurrence occurred in female sex, subtotal resection, and tumors larger than 4.5 cm. Further studies are needed to confirm these findings and determine whether patients without any of these risk factors can undergo surgical resection without adjuvant radiation therapy.

Purpose: We aimed to determine the comparative effectiveness of radiation dose escalation and concurrent chemoradiation therapy (CCRT) in a population-based cohort of patients with stage IV non-small cell lung cancer who underwent palliative thoracic radiation therapy (RT)., Methods and Materials: The cohort consisted of 27,063 patients in the National Cancer Database with stage IV non-small cell lung cancer treated with thoracic RT between 20 and 55 Gy in 2004 to 2011. High- versus intermediate- vs low-dose (HD vs ID vs LD, respectively) RT was defined as biologically effective dose above 50 Gy, between 35 and 50 Gy, and below 35 Gy, respectively. Among patients who received any chemotherapy, separate analyses were performed to examine the impact of CCRT on overall survival (OS)., Results: The median follow-up was 3.9 months for the entire cohort and 18 months for surviving patients. The 5 most common treatment schemes were 30/10 (Gy/fraction, 23% of entire cohort), 35/14 (8%), 37.5/15 (7%), 40/20 (3%), and 50/20 (3%). On multivariable analysis, the survival hazard ratios (HRs) for HD and ID compared with LD RT were 0.37 and 0.51, respectively (P < .0001). Propensity score matching found a superior survival benefit for ID and HD (HR, 0.41 and 0.57 for HD and ID RT, respectively, vs LD, P < .0001). Among those who received any chemotherapy (59% of total), the median OS for patients treated with CCRT (19% of total) was 5.3 versus 5.6 months (P = .667). On multivariable analysis, the HR for CCRT was 1.01 (P = .46)., Conclusions: The delivery of higher-dose RT but not concurrent chemotherapy was associated with a significant improvement of OS. This population-based study supports higher-dose palliative regimens and motivates prospective study of escalation beyond a biologically effective dose of 35 Gy., (Copyright © 2015 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: High-level evidence has established well-recognized standard treatment regimens for patients undergoing palliative chest radiotherapy (RT) for stage IV non-small cell lung cancer (NSCLC), including treating with fewer than 15 fractions of RT, and not delivering concurrent chemoradiation (CRT) because of its increased toxicity and limited efficacy in the palliative setting., Methods: The study included patients in the National Cancer Database from 2004 to 2012 with stage IV lung cancer who received palliative chest radiation therapy. Logistic regression was performed to determine predictors of standard vs nonstandard regimens (>15 fractions or CRT). All statistical tests were two-sided., Results: There were 46 803 patients in the analysis and 49% received radiotherapy for longer than 15 fractions, and 28% received greater than 25 fractions. Approximately 19% received CRT. The strongest independent predictors of long-course RT were private insurance (odds ratio [OR] = 1.40 vs uninsured, 95% confidence interval [CI] = 1.28 to 1.53) and treatment in community cancer programs (OR = 1.49, 95% CI = 1.38 to 1.58) compared with academic research programs. The strongest factors that predicted for concurrent chemoradiotherapy were private insurance (OR = 1.38 95% CI = 1.23 to 1.54) compared with uninsured patients and treatment in community cancer programs (OR = 1.44, 95% CI = 1.33 to 1.56) compared with academic programs., Conclusions: Approximately half of all patients with metastatic lung cancer received a higher number of radiation fractions than recommended. Patients with private insurance and treated in community cancer centers were more likely to receive longer courses of RT or CRT. This demonstrates that a substantial number of patients requiring palliative thoracic radiotherapy are overtreated and further work is necessary to ensure these patients are treated according to evidenced-based guidelines., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Patients unable to receive surgery for stage I non-small cell lung cancer (NSCLC) can undergo conventional radiotherapy (ConvRT), stereotactic body radiotherapy (SBRT), or no treatment (NoTx). This study assessed patterns of care and disparities in the receipt of each of these treatments., Methods: The study included patients in the National Cancer Database from 2003 to 2011 with T1-T2N0M0 inoperable lung cancer (n = 39,822). Logistic regressions were performed to determine predictors of receiving any radiation versus NoTx and for receiving SBRT versus ConvRT., Results: Treatment with radiation was significantly less likely in blacks (odds ratio, OR 0.65) and Hispanics (OR 0.42) compared with whites. Treatment with SBRT versus ConvRT was more likely in an academic research program (OR 2.62) and a high-volume facility (OR 7.00) compared with community cancer programs or low-volume facilities. In 2011, use of SBRT, ConvRT, and NoTx was 25%, 28%, and 46% for patients in a community cancer center versus 68%, 11%, and 21%, respectively, in an academic center (p < 0.0001)., Conclusion: There were marked institutional and socioeconomic variations in the treatment of inoperable stage I NSCLC. These results suggest that removal of barriers to receive radiation therapy and particularly improved access to SBRT may meaningfully improve survival in this disease.

Background: This study examined the comparative effectiveness of no treatment (NoTx), conventional fractionated radiotherapy (ConvRT), and stereotactic body radiotherapy (SBRT) in patients with inoperable stage I non-small cell lung cancer. This population based cohort also allowed us to examine what facility level characteristics contributed to improved outcomes., Methods: We included patients in the National Cancer Database from 2003 to 2006 with T1-T2N0M0 inoperable lung cancer (n=13,036). Overall survival (OS) was estimated using Kaplan-Meier methods and Cox proportional hazard regression., Results: The median follow up was 68months (interquartile range: 35-83months) in surviving patients. Among the cohort, 52% received NoTx, 41% received ConvRT and 6% received SBRT. The 3-year OS was 28% for NoTx, 36% for ConvRT radiotherapy, and 48% for the SBRT cohort (p<0.0001). On multivariate analysis, the hazard ratio for SBRT and ConvRT were 0.67 and 0.77, respectively, as compared to NoTx (1.0 ref) (p<0.0001). Patients treated at a high volume facility vs. low volume facility had a hazard ratio of 0.94 vs. 1.0 (p=0.01)., Conclusions: Patients with early stage inoperable lung cancer treated with SBRT and at a high volume facility had a survival benefit compared to patients treated with ConvRT or NoTx or to those treated at a low volume facility., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: In this study, we examined trends in the radiotherapy dose prescribed and the effect of dose escalation on survival in patients with stage III lung cancer., Materials and Methods: Radiation dose prescription patterns were analyzed for 38,848 patients in the National Cancer Database with clinical stage III disease who underwent concurrent chemoradiation between 2004 and 2011 to a dose between 57 and 80 Gy. Survival information was available for patients diagnosed from 2004 to 2006 (n = 12,024). Overall survival (OS) was estimated using Kaplan-Meier methods. Cox proportional hazard regression was used to estimate hazard ratios (HRs)., Results: The percentage of patients treated to ≥ 64 Gy increased from 50% in 2004 to 62% in 2011 (P < .001). The 5-year OS was 12% for patients treated between 57 and 59.3 Gy, 14% for patients treated at 59.4 to 62.9 Gy, 16% for patients treated at 63 to 66 Gy and 66.1 to 73.9 Gy, and 13% for patients treated at 74 to 80 Gy (P < .0001). In multivariate analysis, the estimated HR (95% confidence interval) was 1.3 (1.1-1.6) for 57 to 59.3 Gy, 1.0 (0.9-1.2) for 59.4 to 62.9 Gy, 0.9 (0.9-1.2) for 63 to 66 Gy, 0.9 (0.8-1.1) for 66.1 to 73.9 Gy, and 1.0 (referent) for the 74 to 80 Gy cohort. There was no significant difference in the HR for the dose groups > 59.4 Gy compared with the 74 to 80 Gy cohort., Conclusion: There was no improvement in OS with radiotherapy dose escalation beyond 59.4 Gy for patients with unresectable clinical stage III lung cancer treated with chemoradiation., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Introduction: Optimal management of clinical stage IIIA-N2 non-small-cell lung cancer (NSCLC) is controversial. This study examines whether neoadjuvant chemoradiation plus surgery improves survival rates when compared with other recommended treatment strategies., Methods: Adult patients from the National Cancer Database, with clinical stage IIIA-N2 disease definitively treated between 1998 and 2004 at American College of Surgeons Commission on Cancer accredited facilities, were included in the study. Treatment was defined as neoadjuvant chemoradiation plus either lobectomy (NeoCRT+L) or pneumonectomy (NeoCRT+P), lobectomy plus adjuvant therapy (L+AT), pneumonectomy plus adjuvant therapy (P+AT), and concurrent chemoradiation (CRT). Median follow-up and overall survival (OS) were defined from date of diagnosis to last contact. Five-year OS was estimated using Kaplan-Meier methods. Cox proportional hazard regression was used to estimate hazard ratios and 95% confidence intervals (CIs), adjusting for sociodemographic, clinical, and facility characteristics., Results: Median follow-up was 11.8 months for 11,242 eligible patients. Five-year OS was 33.5%, 20.7%, 20.3%, 13.35%, and 10.9% for NeoCRT+L, NeoCRT+P, L+AT, P+AT, and CRT, respectively (p < 0.0001). On multivariable analysis, the estimated hazard ratio was 0.51 (CI: 0.45-0.58) for NeoCRT+L; 0.77 (0.63-0.95) for NeoCRT+P; 0.66 (0.59-0.75) for L+AT; 0.69 (0.54-0.88) for P+AT; and 1.0 (reference) for the CRT group. Comorbidity did not attenuate the relationship between treatment and survival., Conclusion: This large study demonstrates that patients with clinical stage IIIA-N2 NSCLC, who underwent neoadjuvant chemoradiation followed by lobectomy, were associated with an improved survival.

Introduction: Literature concerning primary pulmonary sarcomas (PPS) is limited to small case series. This study examines, in a large cohort, the clinical characteristics and therapeutic strategies of PPS and their impact on overall survival (OS)., Methods: This was a retrospective analysis from the Surveillance, Epidemiology, and End Results database (1988-2008). Eligible patients had primary PPS and underwent local therapy. Survival estimates were obtained using the Kaplan-Meier method and the Cox regression model. OS of PPS patients were compared with a cohort of 10,909 patients with extremity soft-tissue sarcomas., Results: The cohort included 365 PPS patients with a median follow-up of 21 months. Fifty-five percent of the patients had large tumors (>5 cm), 76% were high-grade, and 16% had node-positive disease. Seventy-five percent of the cohort underwent surgery alone, 14% underwent surgery and radiation therapy, and 11% underwent radiation therapy alone. Multivariate analysis showed reduced OS for patients with tumors more than 5 cm (hazard ratio [HR] 1.6, 95% confidence interval [CI] 1.25-2.19), high tumor grade (HR 3.1, 95% CI 1.26-3.62), and unresectable disease (HR 2.6, 95% CI 1.76-3.88. The 5-year OS for the cohort of pulmonary sarcomas versus sarcomas of the extremities was 35% versus 71% (p < 0.0001)., Conclusion: This large study examining PPS patients reveals a high rate of nodal involvement and a markedly worse OS than patients with extremity soft-tissue sarcomas. Thus, given the poor overall prognosis, it is recommended that PPS patients undergo a thorough mediastinal nodal evaluation to rule out locoregional metastasis and proceed with aggressive treatment.

Objective: To examine the effect of adjuvant radiation therapy (RT) on survival of high-grade and/or locally advanced malignant major salivary gland tumors (MMSGT)., Patients: The study population comprised 2170 patients with high-grade (poorly differentiated or undifferentiated) and/or locally advanced MMSGT (T3/4 or N+)., Main Outcome Measures: The Surveillance, Epidemiology, and End Results registry was used to obtained data for all patients 20 years or older who underwent surgery for high-grade and/or locally advanced nonmetastatic MMSGT between 1988 and 2005. Univariate and multivariable regression analyses were performed to identify factors associated with improved survival., Results: Seventy-two percent of patients received adjuvant RT, while 28% underwent surgery alone. Patients receiving adjuvant RT were younger and had higher T and N categories and grade. Multivariable analysis revealed significantly improved survival with adjuvant RT (HR for mortality, 0.76; 95% CI, 0.65-0.89; P < .001). Other factors associated with improved survival included younger age at diagnosis, less than radical surgery, certain histologic subtypes, lower grade, and lower T and N categories. Subset analyses found significantly improved survival with adjuvant RT among patients with both high-grade and locally advanced disease (P < .001), involvement of the parotid gland (P = .002), or squamous cell carcinoma (P = .004), with a survival benefit seen among patients with adenocarcinoma that did not reach significance (P = .06)., Conclusions: Adjuvant RT is associated with improved survival for high-grade and/or locally advanced MMSGT based on analysis of this large, population-based database. Further prospective studies are warranted to examine the role of RT in the management of this disease.

Primary lymphomas of mucosa associated lymphoid tissue (MALT) are exceedingly rare. We report the case of a 51 year old female diagnosed with primary MALT lymphoma of the gallbladder after cholecystectomy. Further staging workup was negative for metastatic disease. When the disease is localized to the gallbladder, primary MALT lymphomas of the gallbladder carry an excellent prognosis, and surgical resection is curative in the majority of cases.