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We defined the occult nodal metastasis (ONM) rate of clinical node-negative salivary gland malignancies and examined the role of elective neck dissection (END). Meta-analysis querying four databases, from inception of databases to March 25th, 2020. Fifty-one studies with 11 698 patients were included. ONM rates were 64% for salivary ductal carcinoma (SDC), 51% for undifferentiated carcinoma, 34% for carcinoma ex-pleomorphic adenoma (CXPA), 32% for adenocarcinoma not otherwise specified (ANOS), 31% for lymphoepithelial carcinoma (LE), 20% for mucoepidermoid carcinoma, 17% for acinic cell carcinoma, and 17% for adenoid cystic carcinoma. T3/T4 tumors had a 2.3 times increased risk of ONM than T1/T2 tumors. High-grade tumors had a 3.8 times increased risk of ONM than low/intermediate-grade tumors. ONM rates were exceedingly high for T3/T4, high-grade, and undifferentiated, SDC, ANOS, CXPA, and LE tumors, indicating the potential role of END.

Introduction Traditionally, larger lesions of laryngeal verrucous carcinoma are treated with surgical excision, with definitive radiotherapy generally reserved for smaller lesions. However, data utilizing modern databases is limited. Objective The authors sought to assess, utilizing the National Cancer Database, whether overall survival for patients with laryngeal verrucous carcinoma was equivalent when treated with definitive radiotherapy versus definitive surgery. Methods A retrospective cohort study was conducted utilizing the National Cancer Database. All cases of laryngeal verrucous carcinoma within the National Cancer Database between 2006 and 2014 were reviewed. Patients with T1–T3 (American Joint Commission on Cancer 7th Edition) laryngeal verrucous carcinoma were included and stratified by treatment modality. Demographics, treatment, and survival data were analyzed. Results A total of 392 patients were included. Two hundred and fifty patients underwent surgery and 142 received radiotherapy. The two groups differed in age, transition of care, clinical T stage, and clinical stages. There was no significant difference in survival between T1–T3 lesions treated with surgery or radiotherapy (p = 0.32). Age, comorbidities, insurance status, and clinical T stage impacted overall hazard on multivariate analysis (p Conclusion Overall survival is equivalent for patients with clinical T1 and clinical T2 laryngeal verrucous carcinoma treated with primary radiotherapy versus primary surgery. Thus, radiotherapy should be considered as a non-inferior treatment modality for certain patients with laryngeal verrucous carcinoma.

PURPOSE: More than half of patients with head and neck squamous cell carcinoma (HNSCC) experience a delay initiating guideline-adherent postoperative radiation therapy (PORT), contributing to excess mortality and racial disparities in survival. However, interventions to improve the delivery of timely, equitable PORT among patients with HNSCC are lacking. This study (1) describes the development of NDURE (Navigation for Disparities and Untimely Radiation thErapy), a navigation-based multilevel intervention (MLI) to improve guideline-adherent PORT and (2) evaluates its feasibility, acceptability, and preliminary efficacy. METHODS: NDURE was developed using the six steps of intervention mapping (IM). Subsequently, NDURE was evaluated by enrolling consecutive patients with locally advanced HNSCC undergoing surgery and PORT (n = 15) into a single-arm clinical trial with a mixed-methods approach to process evaluation. RESULTS: NDURE is a navigation-based MLI targeting barriers to timely, guideline-adherent PORT at the patient, healthcare team, and organizational levels. NDURE is delivered via three in-person navigation sessions anchored to case identification and surgical care transitions. Intervention components include the following: (1) patient education, (2) travel support, (3) a standardized process for initiating the discussion of expectations for PORT, (4) PORT care plans, (5) referral tracking and follow-up, and (6) organizational restructuring. NDURE was feasible, as judged by accrual (88% of eligible patients [100% Blacks] enrolled) and dropout (n = 0). One hundred percent of patients reported moderate or strong agreement that NDURE helped solve challenges starting PORT; 86% were highly likely to recommend NDURE. The rate of timely, guideline-adherent PORT was 86% overall and 100% for Black patients. CONCLUSION: NDURE is a navigation-based MLI that is feasible, is acceptable, and has the potential to improve the timely, equitable, guideline-adherent PORT.

OBJECTIVE. Pathologic extranodal extension (ENE) is an important adverse feature for human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC), but the prognostic significance of microscopic ENE (ENE(mi)) and role of adjuvant concurrent chemoradiation (CRT) for ENE(mi) remain unclear. This study evaluates (1) the prognostic significance of ENE(mi) in HPV-negative HNSCC and (2) whether adjuvant CRT is associated with improved overall survival (OS) for these patients. STUDY DESIGN. Retrospective cohort study. SETTING. Commission on Cancer (CoC)–accredited facilities. METHODS. This retrospective cohort study included patients in the National Cancer Database from 2009 to 2015 with pathologic node-positive (pN+) HPV-negative HNSCC with either pathologic ENE(mi) or no ENE who had undergone margin-negative surgery. The association of ENE(mi) with OS was evaluated using Cox proportional hazard analyses. Analyses were repeated in patients with ENE(mi) receiving adjuvant therapy to evaluate the association of adjuvant CRT with OS. RESULTS. We included 5483 patients with pN+ HPV-negative HNSCC, of whom 24% had ENE(mi). On multivariable analysis, ENE(mi) was associated with decreased OS relative to no ENE (adjusted hazard ratio [aHR], 1.43; 95% CI, 1.28-1.59). Among patients with ENE(mi) who received ≥60 Gy of adjuvant radiation therapy (RT) (n = 617), adjuvant CRT was not associated with improved OS relative to RT (aHR, 0.91; 95% CI, 0.66-1.27). CONCLUSION. For patients with HPV-negative HNSCC, pN+ with ENE(mi) is associated with worse OS than pN+ without ENE. However, for patients with ENE(mi), concurrent CRT is not associated with improved OS relative to RT. The optimal adjuvant paradigm for ENE(mi) requires additional investigation.

PURPOSE: Delays initiating guideline-adherent postoperative radiation therapy (PORT) in head and neck squamous cell carcinoma (HNSCC) are common, contribute to excess mortality, and are a modifiable target for improving survival. However, the barriers that prevent the delivery of timely, guideline-adherent PORT remain unknown. This study aims to identify the multilevel barriers to timely, guideline-adherent PORT and organize them into a conceptual model. MATERIALS AND METHODS: Semi-structured interviews with key informants were conducted with a purposive sample of patients with HNSCC and oncology providers across diverse practice settings until thematic saturation (n = 45). Thematic analysis was performed to identify the themes that explain barriers to timely PORT and to develop a conceptual model. RESULTS: In all, 27 patients with HNSCC undergoing surgery and PORT were included, of whom 41% were African American, and 37% had surgery and PORT at different facilities. Eighteen clinicians representing a diverse mix of provider types from 7 oncology practices participated in key informant interviews. Five key themes representing barriers to timely PORT were identified across 5 health care delivery levels: (1) inadequate education about timely PORT, (2) postsurgical sequelae that interrupt the tight treatment timeline (both intrapersonal level), (3) insufficient coordination and communication during care transitions (interpersonal and health care team levels), (4) fragmentation of care across health care organizations (organizational level), and (5) travel burden for socioeconomically disadvantaged patients (community level). CONCLUSION: This study provides a novel description of the multilevel barriers that contribute to delayed PORT. Interventions targeting these multilevel barriers could improve the delivery of timely, guideline-adherent PORT and decrease mortality for patients with HNSCC.

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Trastuzumab is a monoclonal antibody against HER2 (also known as ERBB2). The primary objective of the NRG Oncology/RTOG-1010 trial was to establish whether trastuzumab improves disease-free survival when combined with trimodality treatment (paclitaxel plus carboplatin and radiotherapy, followed by surgery) for patients with untreated HER2-overexpressing oesophageal adenocarcinoma.NRG Oncology/RTOG-1010 was an open label, randomised, phase 3 trial for which patients were accrued from 111 NRG-affiliated institutions in the USA. Eligible patients were adults (aged ≥18 years) with newly diagnosed pathologically confirmed oesophageal adenocarcinoma, American Joint Committee on Cancer 7th edition T1N1-2 or T2-3N0-2 stage disease, and a Zubrod performance status of 0-2. Patients were stratified by adenopathy (no vs yes [coeliac absent] vs yes [coeliac present ≤2 cm]) and randomly assigned (1:1) to receive weekly intravenous paclitaxel (50 mg/m606 patients were entered for HER2 assessment from Dec 30, 2010 to Nov 10, 2015, and 203 eligible patients who were HER2-positive were enrolled and randomly assigned to chemoradiotherapy plus trastuzumab (n=102) or chemoradiotherapy alone (n=101). Median duration of follow-up was 2·8 years (IQR 1·4-5·7). Median disease-free survival was 19·6 months (95% CI 13·5-26·2) with chemoradiotherapy plus trastuzumab compared with 14·2 months (10·5-23·0) for chemoradiotherapy alone (hazard ratio 0·99 [95% CI 0·71-1·39], log-rank p=0·97). Grade 3 treatment-related adverse events occurred in 41 (43%) of 95 patients in the chemoradiotherapy plus trastuzumab group versus 52 (54%) of 96 in the chemoradiotherapy group and grade 4 events occurred in 20 (21%) versus 21 (22%). The most common grade 3 or worse treatment-related adverse events for both groups were haematological (53 [56%] of 95 patients in the chemoradiotherapy plus trastuzumab group vs 55 [57%] of 96 patients in the chemotherapy group) or gastrointestinal disorders (28 [29%] vs 20 [21 %]). 34 (36%) of 95 patients in the chemoradiotherapy plus trastuzumab group and 27 (28%) of 96 patients in the chemoradiotherapy only group had treatment-related serious adverse events. There were eight treatment-related deaths: five (5%) of 95 patients in the chemoradiotherapy plus trastuzumab group (bronchopleural fistula, oesophageal anastomotic leak, lung infection, sudden death, and death not otherwise specified), and three (3%) of 96 in the chemoradiotherapy group (two multiorgan failure and one sepsis).The addition of trastuzumab to neoadjuvant chemoradiotherapy for HER2-overexpressing oesophageal cancer was not effective. Trastuzumab did not lead to increased toxicities, suggesting that future studies combining it with or using other agents targeting HER2 in oesophageal cancer are warranted.National Cancer Institute and Genentech.

Background A chronic imbalance of energy intake and energy expenditure results in excess fat storage. The obesity often caused by this overweight is detrimental to the health of millions of people. Understanding both sides of the energy balance equation and their counter-regulatory mechanisms is critical to the development of effective therapies to treat this epidemic. Scope of review Behaviors surrounding ingestion have been reviewed extensively. This review focuses more specifically on energy expenditure regarding bodyweight control, with a particular emphasis on the organs and attractive metabolic processes known to reduce bodyweight. Moreover, previous and current attempts at anti-obesity strategies focusing on energy expenditure are highlighted. Precise measurements of energy expenditure, which consist of cellular, animal, and human models, as well as measurements of their translatability, are required to provide the most effective therapies. Major conclusions A precise understanding of the components surrounding energy expenditure, including tailored approaches based on genetic, biomarker, or physical characteristics, must be integrated into future anti-obesity treatments. Further comprehensive investigations are required to define suitable treatments, especially because the complex nature of the human perspective remains poorly understood., Molecular Metabolism, 51

Background: Primary management of advanced head/neck cancers involves concurrent chemoradiotherapy . Subsequently, regional and local failures are managed with resection but there have been few reports that describe the morbidity and disease control outcomes of surgical salvage in this setting. Methods: Retrospective analysis describes complications, survival, and patterns of failure after salvage resection of isolated local and/or regional failures of head/neck cancer following definitive concurrent chemoradiotherapy. Results: Sixteen patients were identified for inclusion: laryngectomy in 11 patients, oral cavity/oropharynx resection in 2 patients, and neck dissection alone in 4 patients. Ten patients required graft tissue reconstruction (6 pedicle and 4 free flap). Median post-operative hospitalization was 7 days (range 3-19), and 4 patients required hospital re-admission. At a median survivor follow-up of 15.8 months (range 4.3-34.9), 10 patients were alive (6 without evidence of disease). Seven patients experienced disease recurrence at a median 6.7 months (range 0-12.6) following salvage resection (2 with isolated distant failures). Estimated 2-year local/regional control, freedom from failure, and overall survival were 58%, 39%, and 58%, respectively. Conclusions: Surgical salvage after primary definitive concurrent chemoradiotherapy is feasible with toxicity and outcomes similar to prior radiotherapy alone or sequential chemotherapy and radiation. Local andregional recurrence remains the predominant pattern of failure.

BACKGROUND Patients who travel a long distance (≥50 miles) for cancer care have improved outcomes. However, to the authors' knowledge, the prevalence of long travel distances for treatment by patients with head and neck squamous cell carcinoma (HNSCC), and the effect of travel distance on overall survival (OS), remains unknown. METHODS The authors used the National Cancer Data base from 2004 through 2013 to identify patients with HNSCC undergoing definitive treatment. Travel distance for treatment was categorized as short (

Objective The aim of this study was to determine prognostic value of tumor size and metabolic activity on survival for patients with early stage nonsmall cell lung cancer receiving stereotactic body radiation therapy. Methods We retrospectively evaluated the patients who underwent positron emission tomography-computed tomography scan before stereotactic body radiation therapy treatment. Tumor diameter, tumor volume, maximum standardized uptake value (SUVmax), standardized uptake value (SUV) average, and SUV volume were obtained. Cox regression analyses were performed to determine the associations between tumor characteristics and survival. Results The patients with large tumors and high SUVmax have worse survival than patients with small tumors and low SUVmax (hazard ratio [HR] = 3.47, P = 0.007). Patients with small tumors and high SUVmax (HR = 1.80; P = 0.24) and large tumors and low SUVmax (HR = 1.55; P = 0.43) had increased risk of death compared with patients with small tumors and low SUVmax. Conclusions Both increased tumor size and metabolic activity are associated with increased risk of death. Combining size and metabolic activity together is superior for predicting 2-year survival and identifying patients for whom survival is statistically worse.

Objective The goal of this study is to determine the effect of primary surgery vs radiotherapy (RT) on overall survival (OS) in patients with early stage oral cavity squamous cell carcinoma (OCSCC). In addition, this study attempts to identify factors associated with receiving primary RT. Study Design Retrospective cohort study. Setting National Cancer Database (NCDB, 2004-2013). Subjects and Methods Reviewing the NCDB from 2004 to 2013, patients with early stage I to II OCSCC were identified. Kaplan-Meier estimates of survival, Cox regression analysis, and propensity score matching were used to examine differences in OS between primary surgery and primary RT. Multivariable logistic regression analysis was performed to identify factors associated with primary RT. Results Of the 20,779 patients included in the study, 95.4% (19,823 patients) underwent primary surgery and 4.6% (956 patients) underwent primary RT. After adjusting for covariates, primary RT was associated with an increased risk of mortality (adjusted hazard ratio [aHR], 1.97; 99% confidence interval [CI], 1.74-2.22). On multivariable analysis, factors associated with primary RT included age ≥70 years, black race, Medicaid or Medicare insurance, no insurance, oral cavity subsite other than tongue, clinical stage II disease, low-volume treatment facilities, and earlier treatment year. Conclusion Primary RT for early stage OCSCC is associated with increased mortality. Approximately 5% of patients receive primary RT; however, this percentage is decreasing. Patients at highest risk for receiving primary RT include those who are elderly, black, with public insurance, and treated at low-volume facilities.

BACKGROUND The objective of this study was to determine the effects of National Comprehensive Cancer Network (NCCN) guideline–adherent initiation of postoperative radiation therapy (PORT) and different time-to-PORT intervals on the overall survival (OS) of patients with head and neck squamous cell carcinoma (HNSCC). METHODS The National Cancer Data Base was reviewed for the period of 2006-2014, and patients with HNSCC undergoing surgery and PORT were identified. Kaplan-Meier survival estimates, Cox regression analysis, and propensity score matching were used to determine the effects of initiating PORT within 6 weeks of surgery and different time-to-PORT intervals on survival. RESULTS This study included 41,291 patients. After adjustments for covariates, starting PORT >6 weeks postoperatively was associated with decreased OS (adjusted hazard ratio [aHR], 1.13; 99% confidence interval [CI], 1.08-1.19). This finding remained in the propensity score–matched subset (hazard ratio, 1.21; 99% CI, 1.15-1.28). In comparison with starting PORT 5 to 6 weeks postoperatively, initiating PORT earlier was not associated with improved survival (aHR for ≤ 4 weeks, 0.93; 99% CI, 0.85-1.02; aHR for 4-5 weeks, 0.92; 99% CI, 0.84-1.01). Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements (aHR, 1.09, 1.10, and 1.12 for 7-8, 8-10, and >10 weeks, respectively). CONCLUSIONS Nonadherence to NCCN guidelines for initiating PORT within 6 weeks of surgery was associated with decreased survival. There was no survival benefit to initiating PORT earlier within the recommended 6-week timeframe. Increasing durations of delay beyond 7 weeks were associated with small, progressive survival decrements. Cancer 2017;123:4841-50. © 2017 American Cancer Society.

BACKGROUND Adherence to evidence-based treatment guidelines has been proposed as a measure of cancer care quality. The objective of this study was to determine the rate and predictors of care that does not adhere to National Comprehensive Cancer Network guidelines regarding commencing postoperative radiation therapy (PORT) within 6 weeks of surgery for patients with head and neck squamous cell carcinoma (HNSCC). METHODS The National Cancer Data Base was reviewed from 2006 to 2014, and patients with HNSCC who underwent curative-intent surgery followed by PORT were identified. Multivariable logistic regression analysis was used to determine the factors associated with nonadherence to guidelines regarding the timing of initiating PORT. RESULTS In total, 47,273 patients were included in the study. 55.7% of patients (26,340/47,273) failed to commence PORT within 6 week of surgery. The percentage of patients who failed to initiate PORT within 6 week of surgery increased over time. On multivariable analysis, the factors associated with failure to initiate timely, guideline-adherent PORT included black race, public insurance [Medicare, Medicaid] or uninsured status, lower levels of education, increased severity of comorbidity, increased postoperative length of stay, 30-day unplanned hospital readmission, treatment at an academic medical center, and the receipt of surgery and PORT at different facilities. CONCLUSIONS Over 50% of patients with HNSCC who undergo surgery and PORT receive care that does not adhere to National Comprehensive Cancer Network guidelines with regard to initiating PORT within 6 weeks of surgery. Sociodemographic, oncologic, treatment, and hospital factors are all associated with failure to receive guideline-directed care and should be explored in future studies. Cancer 2017. © 2017 American Cancer Society.

Background The current study was conducted to determine the effect of postoperative radiotherapy (PORT) on overall survival in patients with surgically managed pT3-T4aN0 laryngeal squamous cell carcinoma (SCC). Methods A review of the National Cancer Data Base from 2004 through 2013 was performed. Patients with surgically managed pT3-4aN0 laryngeal SCC with negative surgical margins were included. Univariable and multivariable Cox regression analyses were used to determine factors associated with survival. Results A total of 1460 patients were included, 46.2% of whom had pT3N0 disease (674 patients) and 53.8% of whom had pT4aN0 disease (786 patients). Approximately 72.0% of the patients with pT3N0 disease (485 patients) and 50.1% of the patients with pT4aN0 disease (394 patients) received PORT. PORT was not found to be associated with improved overall survival on univariable analysis for patients with pT3N0 disease (hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62-1.14), but was for patients with pT4aN0 disease (HR, 0.57; 95% CI, 0.45-0.71). For patients with pT3N0 SCC of the larynx, in a multivariable Cox regression analysis adjusting for age >65 years, severity of comorbidities, larynx subsite, extent of laryngectomy, and number of lymph nodes removed, PORT was not found to be associated with improved survival (adjusted HR, 0.88; 95% CI, 0.64-1.21). For patients with pT4aN0 disease, the administration of PORT was associated with improved survival on multivariable analysis adjusting for age >65 years, severity of comorbidities, larynx subsite, number of lymph nodes removed, and type of hospital (adjusted HR, 0.58; 95% CI, 0.46-0.73). Conclusions For patients with surgically managed pT3N0 laryngeal SCC with negative margins, PORT does not appear to be associated with improved survival. Despite a survival benefit, nearly 50% of patients with pT4aN0 laryngeal SCC and negative surgical margins do not receive standard-of-care PORT. Cancer 2017;123:2248-2257. © 2017 American Cancer Society.

Background Concurrent chemoradiotherapy (CCRT) is commonly employed in limited-stage small-cell lung cancer (LS-SCLC); however, the optimal radiotherapy regimen is still unknown. This 3-institution analysis compares long-term disease control and survival outcomes for once- (QD) versus twice-daily (BID) radiotherapy at contemporary doses. Methods and Materials Data were collected for LS-SCLC patients treated with platinum-based CCRT and planned RT doses of > 5940 cGy at > 180 cGy QD or > 4500 cGy at 150 cGy BID. Comparative outcome analyses were performed for treatment groups. Results From 2005 through 2014, 132 patients met inclusion criteria for analysis (80 QD, 52 BID). Treatment groups were well-balanced, excepting higher rate of advanced mediastinal staging, longer interval from biopsy to treatment initiation, and lower rate of prophylactic cranial irradiation for the QD group, as well as institutional practice variation. At median survivor follow-up of 33.5 months (range, 4.6–105.8), 80 patients experienced disease failure (44 QD, 36 BID), and 106 died (62 QD, 44 BID). No differences in disease control or survival were demonstrated between treatment groups. Conclusion The present analysis did not detect a difference in disease control or survival outcomes for contemporary dose QD versus BID CCRT in LS-SCLC.

e16561 Background: CheckMate 025 demonstrated favorable efficacy and safety results for nivolumab monotherapy in previously treated advanced or metastatic renal cell carcinoma (aRCC). However, real-world evidence on treatment patterns and clinical outcomes is limited. Methods: This multi-centre, retrospective cohort study examined treatment patterns and overall survival (OS) in aRCC patients treated with nivolumab monotherapy. Eligible patients who initiated nivolumab at second-line (2L) or beyond (index) between 01 March 2016 and 30 June 2018 were sampled from four UK centers. Data were extracted using an electronic case report form from index to earliest of: most recent visit; death; end of follow up (31 May 2019). Results: Overall , 151 patients were included in analyses (mean age at index 66.9 years, 72.2% male, median follow-up from index 15.2 months), with 109 (72.2%) and 42 (27.8%) receiving nivolumab at 2L and ≥ third-line (3L+), respectively. Key clinical characteristics are outlined in Table 1. All 2L nivolumab patients had received first-line (1L) tyrosine kinase inhibitors (TKI), pazopanib (57.8%), sunitinib (30.3%), or both in sequence (10.1%). After 2L nivolumab, 3L cabozantinib (36/52, 69.2%) was most common. Most 3L nivolumab patients received 2L TKI (31/36, 86.1%) - commonly axitinib (70.9%). After 3L nivolumab, most patients received fourth-line cabozantinib (8/12, 66.7%). Median time on line of therapy (LOT) decreased with LOT progression: from 7.8 months at 1L to 4.6 months at fifth-line (5L). The proportion of patients who discontinued treatment due to adverse events decreased by LOT, (28.6%, 22.7%, 16.0% and 0%, and 34.7%, 28.1%, 0% and 0% from 2L to 5L, overall and for nivolumab treatment, respectively). Overall, median OS from nivolumab initiation was 19.2 months [95% CI, 16.9-27.0]. Patients who received 2L nivolumab had longest median OS (23.0 months [95% CI, 17.2, not reached]), comparable to CheckMate 025 (25.8 months [95% CI, 22.2-29.8]). Median OS for 3L+ nivolumab patients was 12.4 months [95% CI, 8.8, 23.2]. Among 2L nivolumab patients, 73.9%, 46.2%, and 33.6% survived 12, 24, and 36 months, respectively. For the same respective timeframes, 52.4%, 24.7%, and 18.6% of 3L+ nivolumab patients survived. Conclusions: This study provides real-world evidence on the characteristics, treatment patterns and effectiveness of 2L or ≥ 3L nivolumab monotherapy in previously treated aRCC patients. OS results from UK routine clinical care were comparable to those found in CheckMate 025.[Table: see text]

Importance The American Joint Committee on Cancer staging system (Cancer Staging Manual, 8th Edition) for head and neck squamous cell carcinoma (HNSCC) now categorizes human papillomavirus (HPV)–negative HNSCC in a single positive lymph node smaller than 3 cm with pathologic extranodal extension (ENE) as N2a. The standard of care for pathologic ENE is adjuvant chemoradiation therapy (CRT). Whether adding chemotherapy concurrent with adjuvant radiation therapy improves survival in this clinical scenario is unknown. Objective To assess whether adjuvant CRT relative to radiation therapy alone is associated with improved survival among patients with pN2a HPV-negative HNSCC with ENE. Design, Setting, and Participants This retrospective cohort study included 504 patients with pN2a HPV-negative HNSCC with ENE who had undergone margin-negative surgery and adjuvant therapy. The patients were identified from the National Cancer Database from January 1, 2004, to December 31, 2015. Statistical analyses were conducted from September 1, 2019, to April 16, 2020. Main Outcomes and Measures The primary end point was overall survival. The association of adjuvant CRT with overall survival was analyzed using univariate and multivariate Cox proportional hazards regression analyses. Planned subset analyses were conducted in patients younger than 70 years with no comorbidities (the subset most likely to be eligible for a clinical trial of cisplatin-based chemoradiation) and in patients with pT3/T4 disease classification. Results Of 504 patients (mean [SD] age, 60.5 [12.7] years; 319 [63.3%] men; 434 [86.1%] White) with pN2a HPV-negative HNSCC with ENE who had undergone margin-negative surgery and adjuvant therapy, 298 patients (59.1%) received adjuvant CRT. For the overall cohort of patients with pN2a ENE, adjuvant CRT was not associated with improved overall survival relative to adjuvant radiation therapy alone in a multivariate analysis (adjusted hazard ratio, 0.98; 95% CI, 0.74-1.30). Adjuvant CRT was still not associated with improved overall survival in a subset analysis of 304 patients younger than 70 years with no comorbidities (adjusted hazard ratio, 0.98; 95% CI, 0.66-1.45) nor in a subset of 220 patients with pT3/T4 disease classification (adjusted hazard ratio, 1.03; 95% CI, 0.70-1.54). Conclusions and Relevance This study found that for patients with pN2a HPV-negative HNSCC with ENE who underwent margin-negative surgery and adjuvant therapy, adding chemotherapy concurrent with adjuvant radiation therapy was not associated with improved overall survival. Additional research is necessary to identify the optimal treatment paradigm for this clinical scenario.

Background: Delays initiating guideline-adherent postoperative radiation therapy (PORT) in head and neck squamous cell carcinoma (HNSCC) occur in more than 50% of patients and are key drivers of excess mortality and racial disparities in survival. Theory-based multilevel interventions to address delays and racial disparities in timely PORT have not been described and effective interventions to improve timely, equitable PORT are lacking. Purpose: This study aims to describe the development of NDURE (Navigation for Disparities and Untimely Radiation Therapy), a novel theory- based, multilevel intervention to decrease delays starting PORT and evaluate its feasibility, acceptability, and preliminary clinical efficacy. Methods: An intervention mapping approach was used to develop NDURE. Consecutive patients with locally- advanced HNSCC undergoing surgery and PORT were enrolled into a single-arm clinical trial. Results: NDURE targets the determinants of timely, guideline-adherent PORT through the following core functions: 1) patient education, 2) standardization of the process for initiating the discussion of PORT, 3) PORT care plans, 4) provider role definition, 5) referral tracking and follow-up, and 6) transportation assistance. NDURE was feasible, as judged by trial accrual (88% overall; 100% for African Americans) and dropout (n=0). 100% of patients reported moderate/strong agreement that NDURE helped solve challenges starting PORT; 86% were highly likely to recommend NDURE. The rate of timely, guideline-adherent PORT was 86% overall and 100% for African Americans. Conclusions: NDURE is a novel, theory-based, multilevel intervention targeting determinants of timely PORT among HNSCC patients. NDURE is feasible, acceptable, and has potential to improve the timely, equitable, guideline-adherent PORT. These results support conducting a randomized controlled trial to test NDURE’s clinical efficacy. clinicaltrials.gov number NCT04030130 Citation Format: Evan M. Graboyes, Katherine R. Sterba, Hong Li, Graham Warren, Anthony J. Alberg, Elizabeth A. Calhoun, Brian Nussenbaum, Jessica McCay, Courtney H. Marsh, David M. Neskey, John Kaczmar, Anand K. Sharma, Jennifer Harper, Terry A. Day, Chanita Hughes Halbert. Development and evaluation of a theory-based, multilevel intervention to improve the delivery of timely, guideline-adherent adjuvant therapy for patients with head and neck cancer [abstract]. In: Proceedings of the AACR Virtual Conference: Thirteenth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2020 Oct 2-4. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(12 Suppl):Abstract nr PO-231.

Cancers that arise in the head and neck region are comprised of a heterogeneous group of malignancies that include carcinogen- and human papillomavirus (HPV)-driven mucosal squamous cell carcinoma as well as skin cancers such as cutaneous squamous cell carcinoma, basal cell carcinoma, melanoma, and Merkel cell carcinoma. These malignancies develop in critical areas for eating, talking, and breathing and are associated with substantial morbidity and mortality despite advances in treatment. Understanding of advances in the management of these various cancers is important for all multidisciplinary providers who care for patients across the cancer care continuum. Additionally, the recent Coronavirus Disease 2019 (COVID-19) pandemic has necessitated adaptations to head and neck cancer care to accommodate the mitigation of COVID-19 risk and ensure timely treatment. This review explores advances in diagnostic criteria, prognostic factors, and management for subsites including head and neck squamous cell carcinoma and the various forms of skin cancer (basal cell carcinoma, cutaneous squamous cell carcinoma, Merkel cell carcinoma, and melanoma). Then, this review summarizes emerging developments in immunotherapy, radiation therapy, cancer survivorship, and the delivery of care during the COVID-19 era.

Importance Delays in initiation of postoperative radiotherapy (PORT) after surgery for head and neck squamous cell carcinoma (HNSCC) are common, predominantly affect racial minorities, and are associated with decreased survival. Details regarding the care processes that contribute to timely, equitable PORT remain unknown. Objective To determine care processes associated with timely, equitable PORT. Design, Setting, and Participants This retrospective cohort study included patients 18 years or older undergoing surgery for HNSCC at the Medical University of South Carolina (MUSC), Charleston, followed by PORT (at MUSC or elsewhere) with or without chemotherapy from January 1, 2014, through December 31, 2016. Data were analyzed from September 15, 2017, through June 28, 2018. Main Outcomes and Measures The main outcome measure was the proportion of timely, guideline-adherent initiation of PORT (≤6 weeks postoperatively). Secondary outcome measures included care processes associated with timely PORT. The association between process variables with timely PORT was explored using multivariable logistic regression analysis. Effect modification of the association between receipt of care processes and timely PORT by race was explored using interaction effects. Results A total of 197 patients were included in the analysis; they were predominantly white (157 [79.7%]) and male (136 [69.0%]) with a mean age of 59 years (range, 28-89 years). Overall, 89 patients (45.2%) experienced a delay initiating PORT. African American patients had a 13.5% absolute increase in the rate of delayed PORT relative to white patients (21 of 37 [56.8%] vs 68 of 157 [43.3%]). The adjusted multivariable regression showed that the following care processes were associated with timely PORT: preoperative radiotherapy consultation (odds ratio [OR], 8.94; 95% CI, 1.64-65.53), PORT at MUSC (OR, 6.21; 95% CI, 1.85-24.75), pathology report within 7 postoperative days (OR, 4.14; 95% CI, 1.21-15.86), time from surgery to PORT referral of no longer than 10 days (OR, 12.14; 95% CI, 3.14-63.00), time from PORT referral to consultation of no longer than 10 days (OR, 10.76; 95% CI, 3.01-49.70), and time from PORT consultation to its start of no longer than 21 days (OR, 4.80; 95% CI 1.41-18.44). Analysis of interactions revealed no statistically significant differences between African American and white patients in receipt of key processes associated with timely PORT. Conclusions and Relevance Specific care processes are associated with guideline-adherent initiation of PORT. Novel strategies appear to be needed to ensure that these processes are performed for all patients with HNSCC, thereby facilitating timely, equitable PORT.

Service firms routinely enhance their offerings to satisfy and retain current customers and to attract new customers. We show theoretically that service improvements can be prioritized by simultaneously taking into account the likely incremental revenue (through increased customer value) and the incremental cost of making the improvement. The customer values obtained from a sample of respondents, and cost estimates obtained from managers of the service providing organization are combined to prioritize improvements using a ‘bang for the buck’ (i.e. value/cost) rule. Such a prioritization would be helpful to come up with a ‘short list’ of service improvements. The items on the short list can be evaluated in detail for their ‘Return on Quality’. The approach for prioritization is illustrated in the context of improving passenger train service between a pair of cities in India. An adaptive self-explicated approach is used for obtaining customer values and cost estimates. The customer values so elicited displa...

Purpose: To investigate the toxicity, survival and patterns of failure in patients with advanced lung cancer treated with intensity modulated radiation therapy (IMRT) and chemotherapy. Methods and Materials: Retrospective chart review of 68 total patients: 46 academic and 22 community center. Endpoints: Grade ≥ 3 pneumonitis, Grade ≥ 2 esophagitis, local, regional and distant failure, progression-free survival (PFS) and overall survival (OS). Results: For the academic center patients, median follow-up was 19.2 months. Esophagitis: 0% Grade 3, 35% Grade 2, no significant difference between dose bins

Background The purpose of this study was to present our analysis of outcomes, prognostic factors, and treatment for cervical esophageal carcinoma using the Surveillance, Epidemiology, and End Results (SEER) database. Methods A query of the SEER database from 1998 to 2008 was performed for patients with nonmetastatic adenocarcinoma or squamous cell carcinoma (SCC) of the cervical esophagus. Disease-specific survival (DSS) rates were calculated using Kaplan–Meier method, and predictive factors were analyzed by Cox proportional hazards regression. Results We identified 362 patients; 92% of the patients had SCC, 16% received no definitive therapy, 5% received surgery, 71% received radiation therapy (RT), and 8% received both. Chemotherapy data were not available. Median DSS was 49 months for adenocarcinoma and 15 months for SCC. On multivariate analysis, histology (p = .02), RT (p < .001), and surgery plus RT (p < .001) were associated with DSS. Conclusion Survival in patients with cervical esophageal carcinoma remains poor. Further studies should define the use of RT, surgery, and chemotherapy. © 2014 Wiley Periodicals, Inc. Head Neck 37: 808–814, 2015

Aims: S-nitrosylation and S-glutathionylation, redox-based modifications of protein thiols, are recently emerging as important signaling mechanisms. In this study, we assessed S-nitrosylation-based regulation of Janus-activated kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway that plays critical roles in immune/inflammatory responses and tumorigenesis. Results: Our studies show that STAT3 in stimulated microglia underwent two distinct redox-dependent modifications, S-nitrosylation and S-glutathionylation. STAT3 S-nitrosylation was associated with inducible nitric oxide synthase (iNOS)-produced nitric oxide (NO) and S-nitrosoglutathione (GSNO), whereas S-glutathionylation of STAT3 was associated with cellular oxidative stress. NO produced by iNOS or treatment of microglia with exogenous GSNO inhibited STAT3 activation via inhibiting STAT3 phosphorylation (Tyr705). Consequently, the interleukin-6 (IL-6)-induced microglial proliferation and associated gene expressions were also reduced. In cell-free kinase assay using purified JAK2 and STAT3, STAT3 phosphorylation was inhibited by its selective preincubation with GSNO, but not by preincubation of JAK2 with GSNO, indicating that GSNO-mediated mechanisms inhibit STAT3 phosphorylation through S-nitrosylation of STAT3 rather than JAK2. In this study, we identified that Cys259 was the target Cys residue of GSNO-mediated S-nitrosylation of STAT3. The replacement of Cys259 residue with Ala abolished the inhibitory role of GSNO in IL-6-induced STAT3 phosphorylation and transactivation, suggesting the role of Cys259 S-nitrosylation in STAT3 phosphorylation. Innovation: Microglial proliferation is regulated by NO via S-nitrosylation of STAT3 (Cys259) and inhibition of STAT3 (Tyr705) phosphorylation. Conclusion: Our results indicate the regulation of STAT3 by NO-based post-translational modification (S-nitrosylation). These findings have important implications for the development of new therapeutics targeting STAT3 for treating diseases associated with inflammatory/immune responses and abnormal cell proliferation, including cancer. Antioxid. Redox Signal. 20, 2514–2527.

Adherence to evidence-based treatment guidelines has been proposed as a measure of cancer care quality. The objective of this study was to determine the rate and predictors of care that does not adhere to National Comprehensive Cancer Network guidelines regarding commencing postoperative radiation therapy (PORT) within 6 weeks of surgery for patients with head and neck squamous cell carcinoma (HNSCC).The National Cancer Data Base was reviewed from 2006 to 2014, and patients with HNSCC who underwent curative-intent surgery followed by PORT were identified. Multivariable logistic regression analysis was used to determine the factors associated with nonadherence to guidelines regarding the timing of initiating PORT.In total, 47,273 patients were included in the study. 55.7% of patients (26,340/47,273) failed to commence PORT within 6 week of surgery. The percentage of patients who failed to initiate PORT within 6 week of surgery increased over time. On multivariable analysis, the factors associated with failure to initiate timely, guideline-adherent PORT included black race, public insurance [Medicare, Medicaid] or uninsured status, lower levels of education, increased severity of comorbidity, increased postoperative length of stay, 30-day unplanned hospital readmission, treatment at an academic medical center, and the receipt of surgery and PORT at different facilities.Over 50% of patients with HNSCC who undergo surgery and PORT receive care that does not adhere to National Comprehensive Cancer Network guidelines with regard to initiating PORT within 6 weeks of surgery. Sociodemographic, oncologic, treatment, and hospital factors are all associated with failure to receive guideline-directed care and should be explored in future studies. Cancer 2017;123:2651-60. © 2017 American Cancer Society.

The current study was conducted to determine the effect of postoperative radiotherapy (PORT) on overall survival in patients with surgically managed pT3-T4aN0 laryngeal squamous cell carcinoma (SCC).A review of the National Cancer Data Base from 2004 through 2013 was performed. Patients with surgically managed pT3-4aN0 laryngeal SCC with negative surgical margins were included. Univariable and multivariable Cox regression analyses were used to determine factors associated with survival.A total of 1460 patients were included, 46.2% of whom had pT3N0 disease (674 patients) and 53.8% of whom had pT4aN0 disease (786 patients). Approximately 72.0% of the patients with pT3N0 disease (485 patients) and 50.1% of the patients with pT4aN0 disease (394 patients) received PORT. PORT was not found to be associated with improved overall survival on univariable analysis for patients with pT3N0 disease (hazard ratio [HR], 0.84; 95% confidence interval [95% CI], 0.62-1.14), but was for patients with pT4aN0 disease (HR, 0.57; 95% CI, 0.45-0.71). For patients with pT3N0 SCC of the larynx, in a multivariable Cox regression analysis adjusting for age65 years, severity of comorbidities, larynx subsite, extent of laryngectomy, and number of lymph nodes removed, PORT was not found to be associated with improved survival (adjusted HR, 0.88; 95% CI, 0.64-1.21). For patients with pT4aN0 disease, the administration of PORT was associated with improved survival on multivariable analysis adjusting for age65 years, severity of comorbidities, larynx subsite, number of lymph nodes removed, and type of hospital (adjusted HR, 0.58; 95% CI, 0.46-0.73).For patients with surgically managed pT3N0 laryngeal SCC with negative margins, PORT does not appear to be associated with improved survival. Despite a survival benefit, nearly 50% of patients with pT4aN0 laryngeal SCC and negative surgical margins do not receive standard-of-care PORT. Cancer 2017;123:2248-2257. © 2017 American Cancer Society.

Purpose: Here we report a phase II clinical trial, which was designed to test a novel hypothesis that treatment with gemcitabine (GEM)/doxorubicin (DOX) would be efficacious via reconstitution of C18-ceramide signaling in head and neck squamous cell carcinoma (HNSCC) patients for whom first-line platinum-based therapy failed. Experimental Design: Patients received GEM (1,000 mg/m2) and DOX (25 mg/m2) on days 1 and 8, every 21 days, until disease progression. After completion of 2 treatment cycles, patients were assessed radiographically, and serum samples were taken for sphingolipid measurements. Results: We enrolled 18 patients in the trial, who were evaluable for toxicity, and 17 for response. The most common toxicity was neutropenia, observed in 9 of 18 patients, and there were no major nonhematologic toxicities. Of the 17 patients, 5 patients had progressive disease (PD), 1 had complete response (CR), 3 exhibited partial response (PR), and 8 had stable disease (SD). The median progression-free survival was 1.6 months (95% CI: 1.4–4.2) with a median survival of 5.6 months (95% CI: 3.8–18.2). Remarkably, serum sphingolipid analysis revealed significant differences in patterns of C18-ceramide elevation in patients with CR/PR/SD in comparison with patients with PD, indicating the reconstitution of tumor suppressor ceramide generation by GEM/DOX treatment. Conclusions: Our data suggest that the GEM/DOX combination could represent an effective treatment for some patients with recurrent or metastatic HNSCC, and that serum C18-ceramide elevation might be a novel serum biomarker of chemotherapy response. Clin Cancer Res; 17(18); 6097–105. ©2011 AACR.

Introduction: Management of medically inoperable non-small-cell lung cancer (NSCLC) has been historically challenging, with poor rates of local control and disease-specific survival. Nearly all published series of standard fractionation radiotherapy have utilised doses

Summary Introduction: Major randomised trials have employed elective nodal irradiation as part of combined modality therapy for limited-stage small-cell lung cancer (SCLC). The present investigation describes patterns of failure, disease control, and survival outcomes for involved-field radiotherapy with concurrent chemotherapy, without elective irradiation of uninvolved mediastinal nodal regions. Methods: Retrospective analysis of SCLC patients treated with curative-intent accelerated, twice-daily radiotherapy and concurrent platinum-based chemotherapy at an academic institution. Treatment fields were reviewed, and patients who completed ≥42 Gy in 1.5 Gy twice-daily fractions to involved fields (without elective irradiation of uninvolved mediastinal lymphatic regions) were included in the present analysis. Initial patterns of failure, disease control and overall survival were recorded. Results: Fifty-two patients fulfilled study criteria and were included in the present analysis. All but one patient completed three to four cycles of chemotherapy, and 10 patients experienced grade 3 acute esophagitis. At a median survivor follow-up of 35 months (range 5.5–91.9), 22 patients were alive (15 without recurrence) and 30 had died (23 of/with disease, four of unknown cause, two of other cause and one of treatment toxicity). Initial site(s) of disease failure were loco-regional only (11 patients), distant only (14) and loco-regional plus distant (3). There were no cases of isolated out-of-field mediastinal recurrence in the absence of supraclavicular or more distant disease. The estimated 3-year disease-free and overall survivals were 36% and 44%, respectively. Conclusions: Involved-field radiotherapy did not appear to have an adverse impact on the anticipated patterns of failure, disease control, or overall survival in this population of limited-stage SCLC patients.

To compare toxicities, disease control, and survival outcomes for patients treated with either cisplatin/irinotecan versus carboplatin/paclitaxel concurrent chemoradiotherapy for locally advanced esophageal cancer.Single-institution retrospective comparison between treatment groups: the cisplatin/irinotecan group was treated with 2 cycles of induction chemotherapy followed by concurrent chemoradiotherapy, whereas the carboplatin/paclitaxel group began with chemoradiotherapy followed by 2 additional cycles of chemotherapy. Acute toxicities, response rates, disease control, survival outcomes, and patterns of failure were compared between the groups.Between January 2000 and December 2007, 57 patients were identified for inclusion in the present study (38 cisplatin/irinotecan and 19 carboplatin/paclitaxel). Groups were well-balanced by clinical-, pathologic-, staging-, and treatment-related factors. Thirty-five patients (92%) in the cisplatin/irinotecan group and 18 patients (95%) in the carboplatin/paclitaxel group completed the concurrent phase of chemoradiotherapy. There were no significant differences in hematologic or nonhematologic toxicities between the groups. At a median survivor follow-up of 37.6 months (range: 7.3-59.3 months) for the entire population, 22 patients were alive (16 without evidence of disease). The 3-year overall survival estimates was 19.7% for the cisplatin/irinotecan group versus 56.1% for the carboplatin/paclitaxel group (P = 0.022). Estimated 3-year cancer-specific survivals were 24.6% for the cisplatin/irinotecan group versus 59.3% for the carboplatin/paclitaxel group (P = 0.033).Concurrent chemoradiotherapy with carboplatin/paclitaxel is well-tolerated and provided superior overall and disease-specific survival compared with cisplatin/irinotecan chemoradiotherapy in the present study population. Further investigation is warranted.

e13542Background: NCCN Guidelines recommend smoking cessation support for patients who report smoking within the past 30 days. However, few reports have evaluated the utility of standardized questi...

Objectives/Hypothesis: The optimal concurrent chemoradiotherapy regimen for definitive treatment of locoregionally advanced head and neck cancer remains to be determined. The present investigation reports toxicities, disease control, patterns of failure, and survival outcomes in a large mature cohort of patients treated with low-dose weekly platinum-based concurrent chemoradiotherapy. Study Design: Retrospective single-institution series. Methods: Toxicity and outcome data for locoregionally advanced head and neck cancer patients treated with low-dose weekly platinum-based chemotherapy concurrent with standard fractionation radiotherapy were retrospectively collected and analyzed from a clinical database. Survival analysis methods, including Kaplan-Meier estimation and competing risks analysis, were used to assess locoregional disease control, freedom from failure, and overall survival. Results: Ninety-six patients were eligible for the present analysis. Nearly all patients had American Joint Committee on Cancer clinical stage III to IVB disease (99%). Severe acute toxicities included grade 3 mucositis (61%), grade 3/4 nausea (27%/1%), and grade 3 neutropenia (8%). Thirty-seven patients (38%) required hospitalization for a median of 7 days (range, 1–121). Ninety-two percent of patients completed the fully prescribed course of radiotherapy, and 87% completed ≥6 cycles of chemotherapy. At a median survivor follow-up of 40 months (range, 8–68), 47% of patients were without evidence of disease recurrence. The estimated 4-year freedom from failure and overall survival were 48% and 58%, respectively. Initial site(s) of disease failure were locoregional for 22 patients, locoregional and distant (five patients), and distant only (14 patients). Conclusions: Weekly low-dose platinum-based chemotherapy with full-dose daily radiotherapy is a tolerable alternative regimen for locoregionally advanced head and neck cancers, with comparable efficacy and patterns of failure to alternative regimens. Laryngoscope, 2010

Purpose To describe incidence and identify factors associated with development of severe acute esophagitis during hyperfractionated radiotherapy with concurrent chemotherapy (BID-CRT) in patients with limited-stage small-cell lung cancer (SCLC). Methods and Materials Retrospective cohort analysis of patient-, tumor-, and treatment-related variables was performed to identify factors associated with Radiation Therapy Oncology Group (RTOG) Grade 3 acute esophagitis. Twice-daily chemoradiotherapy (BID-CRT) involved 45 Gy at 1.5 Gy per fraction, treated twice daily with concurrent platinum-based chemotherapy. Logistic regression analyses were used to identify factors associated with esophagitis. Results Between June 1999 and June 2007, 48 patients underwent curative intent BID-CRT for SCLC and were included in the analysis. Median radiotherapy dose was 45 Gy (range, 42–51 Gy) delivered with a median 4 cycles of chemotherapy (range, 2–6). RTOG Grade 3 acute esophagitis developed in 11 patients. No patient developed Grade 4 or 5 esophagitis. Simple logistic regression analyses demonstrated a highly significant association between Grade 3 acute esophagitis and mean esophageal dose ( p = 0.002) as well as relative volume dosimetric area under curve (RV-AUC; p = 0.004). Using multiple regression analysis, RV-AUC was identified as the only factor associated with Grade 3 esophagitis ( p = 0.004). The most strongly associated dosimetric volume was the V15 (Grade 3 esophagitis rates of 15% vs. 64% for V15 Conclusions RV-AUC is the factor most associated with development of Grade 3 acute esophagitis in limited stage SCLC patients receiving BID-CRT.

Background. Reirradiation of locoregionally recurrent, previously irradiated head/neck cancer may be considered in situations of unresectability, medical inoperability, or adverse pathologic features found at salvage resection. Methods. Retrospective cohort analysis of toxicity and survival outcomes in locoregionally recurrent, previously irradiated patients with head/neck cancer treated with hyperfractionated split-course radiotherapy and concurrent chemotherapy. Results. Between March 1998 and September 2006, 39 patients initiated reirradiation at median of 2.3 years (range, 0.5–19) following prior radiotherapy. At median survivor follow-up of 24.5 months (range, 3–63.9), 10 patients are alive without evidence of disease. Median survival is 19.0 months, with estimated 1-, 2-, and 3-year overall survivals of 60.1%, 45.1%, and 22.7%, respectively. Locoregional failure was the predominant site of postreirradiation recurrence. Male sex, total radiotherapy dose, cycles of chemotherapy completed, and clinical response were associated with improved overall survival. Conclusions. Reirradiation can offer long-term survival for patients with recurrent, previously irradiated head/neck cancers. © 2009 Wiley Periodicals, Inc. Head Neck, 2009

Seven head and neck cancer patients participated in a driving evaluation in a driving simulator. Radiation dose on the temporal lobes was moderately associated with time to complete a cognitive test and with driving performance. Results indicated that incidental irradiation may contribute to a decrease in cognition and in unsafe driving performance, which seems to be time-dependent.

Background: There has been an increasing focus on late functional effects of head and neck cancer (HNC) treatment. This study was undertaken to evaluate the incidence of late proximal esophageal stricture in patients undergoing total laryngectomy (TL) and radiation therapy (RT). Material and Methods: An institutional retrospective review of HNC patients treated between 1995 and 2003 with TL and RT was undertaken. Thirty-three patients with stage II–IV disease were included; 25 patients had TL and postoperative RT (group 1), while 8 patients had definitive RT with salvage laryngectomy (group 2). Results: The median follow-up was 28 months. At the last follow-up, 25 patients (76%) were alive and disease free. Four had died and 3 developed distant metastasis. Dysphagia or stenosis developed in 40% in group 1 and 75% in group 2 patients. The median time to dysphagia was 5.5 months for all patients. Conclusions: The incidence of esophageal stenosis was 33% for all patients. Contributing factors for esophageal stenosis after TL and RT include continued alcohol and tobacco use, the dose-volume relationship of the RT and normal tissue damage from the tumor and the treatment.

INTRODUCTION: This study tested the hypothesis that ABT-888 (veliparib), a poly (ADP-ribose) polymerase (PARP) inhibitor, can modulate temozolomide (TMZ) resistance in recurrent, TMZ-refractory glioblastoma (GBM) patients. METHODS: The combination regimen (TMZ/ABT-888) was tested using 2 randomized schedules (5 or 21 days of a 28 day cycle). Two cohorts were studied: bevacizumab naive (BEV-N), and BEV refractory (BEV-R). Six-month progression free survival (PFS6) was the primary endpoint, with hypothesized rates of 30% for BEV-N and 15% for BEV-R; using one-sample binomial tests; alpha = 0.10 and 90% power. Arm 1 combined 40 mg BID ABT-888 with TMZ using the 21/ 28 day schedule at 75 mg/m2. Arm 2 combined ABT-888 (40 mg BID) with TMZ using the 5/ 28 day TMZ at 150-200 mg/m2. RESULTS: Of 151 BEV-N and 74 BEV-R patients, 10 were ineligible. The incidence rate of grade 3/4 myelosuppression was 20.0%. For both arms, PFS6 for BEV-N was 17.0%; 4.4% for BEV-R. Median overall survival (OS) was 10.3 months (95% CI, 8.4-12.0) for BEV-N and 4.7months (95%CI, 3.5-5.6) for BEV-R. The median PFS was essentially the same for both arms and both cohorts at ∼2.0M (95% CI, 1.9-2.1). CONCLUSIONS: The combination of TMZ and ABT-888 did not significantly improve PFS6 for either BEV-N or BEV-R patients with recurrent GBM who had been previously treated with TMZ. For both groups of patients, the objective response rate was low, and did not differ by treatment arm, and the OS and PFS were similar for both treatment arms. Although MGMT status was not included for eligibility and therefore not analyzed, the low response rates, low PFS and low OS suggest that the likelihood of a clinically meaningful benefit for an MGMT-defined subset is remote. Support: Supported by grants U10CA21661, U10CA180868, U10CA180822, U10CA37422, and UG1CA189867 from the National Cancer Institute (NCI) and AbbVie.

Background: Retrospective analysis of patients with medically inoperable non-small cell lung cancer treated with continuous high-dose external beam radiation therapy at the Medical University of South Carolina. Methods: We identified 35 patients with non-small cell lung cancer treated 1998-2002. None were candidates for resection for reasons including: pulmonary function ( n = 23), previous cancer ( n = 9), other co-morbidities ( n = 2), and refusal of surgery ( n = 1). Median percent predicted forced expiratory volume in 1 second was 41.5%. Median age was 71 years. Five patients had more than one primary tumor: three were concurrently treated, two were sequentially treated. Lesion sizes were n = 24); 3-5 cm ( n = 12), and >5 cm ( n = 5). Nodal stage was as follows: N0 ( n = 33) and N1 ( n = 2). Radiation therapy was administered once daily: median dose was 80.5 Gy/35 fx/2.3 Gy/fx. The clinical target volume was tumor plus nodes ≥1.0 cm. V 20 data were available for 12 patients, with a mean value of 15.7%. Results: Thirty-four patients completed treatment. Median follow-up was 23.0 months. There were 26 deaths: 19 died from non-small cell lung (73%) and seven died from co-morbid illness (27%). Median survival was 24 months (95% CI, 18.0-31.9 months). Four patients were alive with disease, and five were alive disease-free at 10- and 68-month follow-ups. Of 41 lesions, local failure occurred in 15 lesions (37%) of which 3 local failure patients (9%) failed concomitantly in untreated regional lymph nodes. There were no isolated nodal recurrences. Distant progression: 10 patients (29%) of which 6 distant progression without local failure. Two patients who both had prior lobectomies experienced grade 5 toxicities. Conclusion: Continuous high-dose external beam radiation therapy 80.5 Gy administered in 35 fractions was tolerated. Treatment-related death was rare (6%) and isolated to patients with prior lobectomies in an extremely high-risk population. Most mortality was lung cancer-related. The dose of 80.5 Gy in 7 weeks is supported for patients with single lesions and no prior lobectomy. Local failure dominates and higher effective doses should be explored.