Background: Limited treatment options are available for oral mucositis, a common, debilitating complication of cancer therapy. We examined the association between daily delivery time of radiotherapy and the severity of oral mucositis in patients with head and neck cancer. Methods: We used electronic medical records of 190 patients with head and neck squamous cell carcinoma who completed radiotherapy, with or without concurrent chemotherapy, at Roswell Park Comprehensive Cancer Center (Buffalo, NY) between 2015 and 2017. Throughout a 7-week treatment course, patient mouth and throat soreness (MTS) was self-reported weekly using a validated oral mucositis questionnaire, with responses 0 (no) to 4 (extreme). Average treatment times from day 1 until the day before each mucositis survey were categorized into seven groups. Multivariable-adjusted marginal average scores (LSmeans) were estimated for the repeated- and maximum-MTS, using a linear-mixed model and generalized-linear model, respectively. Results: Radiation treatment time was significantly associated with oral mucositis severity using both repeated-MTS (n = 1,156; P = 0.02) and maximum-MTS (n = 190; P = 0.04), with consistent patterns. The severity was lowest for patients treated during 8:30 to <9:30 am (LSmeans for maximum-MTS = 2.24; SE = 0.15), increased at later treatment times and peaked at early afternoon (11:30 am to <3:00 pm, LSmeans = 2.66-2.71; SEs = 0.16/0.17), and then decreased substantially after 3 pm. Conclusions: We report a significant association between radiation treatment time and oral mucositis severity in patients with head and neck cancer. Impact: Although additional studies are needed, these data suggest a potential simple treatment time solution to limit severity of oral mucositis during radiotherapy without increasing cost.

Objectives Positron-emission tomography (PET) has improved identification of the primary tumor as well as occult nodal burden in cancer of the head and neck. Nevertheless, there are still patients where the primary tumor cannot be located. In these situations, the standard of care is comprehensive head and neck radiation therapy however it is unclear whether this is necessary. This study examines the effects of radiation treatment volume on outcomes among using data from two cancer centers in unknown primary carcinoma of the head and neck. Methods Patients received unilateral (n = 34), or bilateral radiation (n = 28). Patient factors such as age, gender, smoking history, and patterns of failure were compared using Mann Whitney U and Chi Square. Overall survival (OS) and disease free survival (DFS) trends were estimated using Kaplan-Meier survival curves. Effect of treatment volume on survival was examined using multivariate cox proportional hazard regression model. Results No significant differences were observed in the frequency of local (p = 0.32), regional (p = 0.50), or distant (p = 0.76) failures between unilateral and bilateral radiation therapy. By Kaplan-Meier estimates, OS (3-year OS bilateral = 71.67%, unilateral = 77.90%, p = 0.50) and DFS (3-year DFS bilateral = 77.92%, unilateral = 69.43%, p = 0.63) were similar between the two treatment approaches. Lastly, multivariate analysis did not demonstrate any significant differences in outcome by treatment volumes (OS: HR = 0.74, 95% CI: 0.31, 1.81, p = 0.51; DFS: HR: 0.68, 95% CI: 0.24, 1.93, p = 0.47). Conclusions Unilateral radiation therapy compared with bilateral produced similar survival.

Question Is nonsteroidal anti-inflammatory drug (NSAID) use associated with a survival advantage in patients with head and neck squamous cell carcinoma who are treated with definitive chemoradiation therapy? Findings In this cohort study of 460 patients, NSAID use was associated with significantly better overall survival at 5 years compared with no use of concurrent NSAIDs. Meaning These findings suggest there may be an overall survival advantage for patients with head and neck squamous cell carcinoma who take NSAIDs during chemoradiation. This cohort study investigates the association between nonsteroidal anti-inflammatory drug (NSAID) use and survival in patients with head and neck squamous cell carcinoma treated with chemoradiation therapy (CRT) at a single institution between 2005 and 2017. Importance Nonsteroidal anti-inflammatory drugs (NSAIDs), such as aspirin, are commonly prescribed medications with anti-inflammatory and antiplatelet properties used long term to decrease the risk of cardiovascular events. A recent study showed that aspirin was associated with improved survival in patients with head and neck squamous cell carcinoma (HNSCC) who were treated with surgery. Objective To examine whether use of NSAIDs during definitive chemoradiation therapy (CRT) was associated with improved outcomes in patients with HNSCC. Design, Setting, and Participants This cohort study analyzed patients with HNSCC who were treated with CRT at a single institution between January 1, 2005, and August 1, 2017. Patient and tumor characteristics included age, race/ethnicity, smoking status, alcohol use, comorbidities (respiratory, cardiovascular, immune, renal, endocrine), disease stage, human papillomavirus status, and treatment duration. Data were analyzed from May 1, 2019, to March 17, 2020. Exposures Patients were dichotomized by NSAID use during treatment. Main Outcomes and Measures The association of NSAID use with patterns of failure, disease-specific survival (DSS), and overall survival (OS) was examined using multivariate Cox proportional hazard regression models. Survival estimates for OS and DSS were generated using Kaplan-Meier survival curves. Results A total of 460 patients (median [interquartile range] age, 60 [53.9-65.6] years; 377 [82.0%] men) were included in the analysis. Among these patients, 201 (43.7%) were taking NSAIDs during treatment. On univariate analysis, NSAID use (hazard ratio [HR], 0.63; 95% CI, 0.43-0.92; P = .02) was associated with better OS. On Cox regression analysis, after backward selection adjustment for potentially confounding factors (age, smoking status, primary tumor site, human papillomavirus status, diabetes, stroke, hyperlipidemia), NSAID use remained significantly associated with better OS (HR, 0.59; 95% CI, 0.38-0.90; P = .02). NSAID use was associated with significantly better OS at 5 years compared with patients who did not take concurrent NSAIDs (63.6% [56 of 88 patients]; 95% CI, 58%-73% vs 56.1% [83 of 148 patients]; 95% CI, 50%-63%; P = .03). NSAID use was not associated with better DSS in univariate (HR, 0.82; 95% CI, 0.48-1.41; P = .47) or multivariate (HR, 0.98; 95% CI, 0.57-1.70; P = .44) analysis. NSAID use was not associated with better response to treatment (HR, 1.44; 95% CI, 0.91-2.27; P = .12) or distant failure (HR, 1.12; 95% CI, 0.68-1.84; P = .65). Change in local control with NSAID use was not statistically significant (HR, 0.59; 95% CI, 0.31-1.10; P = .10). Conclusions and Relevance This cohort study suggests a possible OS advantage for patients taking NSAIDs during chemoradiation for HNSCC. Further studies examining this association are warranted.

The study objective was to assess if the extent of neck dissection among patients who receive adjuvant radiotherapy affects regional recurrence and survival. This was a retrospective study of patients who had clinical metastatic mucosal primary squamous cell carcinoma (SCC) to cervical lymph nodes done at Roswell Park Comprehensive Cancer Center, Buffalo, New York from 2004 to 2015. Patients with previous radiotherapy and/or chemotherapy were excluded. All patients had surgery to the primary tumor and the neck followed by adjuvant (chemo) radiation. Patients have been divided into 2 groups according to type of neck dissection as either selective neck dissection (SND) or comprehensive neck dissection (CND). The extent of neck dissection was determined by surgeon preference. All patients received postoperative radiotherapy to the primary tumor bed and to the neck with or without chemotherapy. Main outcomes were measured in regional recurrence and overall survival. In our study, 74 patients were included. Among the 2 groups of patients, 3-year outcomes for regional recurrence occurred in 4 (7.1%) of 56 patients in the SND group and 2 (11.1%) of 18 patients in the CND group. Overall survival was 29 (51.8%) of 56 patients in the SND group and 11 (61.1%) of 18 patients in the CND group ( P = .497). Among patients who died in each cohort, disease-specific death was 20 (74.1%) of 27 patients in the SND group and 5 (71.4%) of 7 patients in the CND group ( P = .79).The overall and disease-specific survival differences between the SND and CND cohorts were not statistically significant. In conclusion, SND, combined with proper adjuvant treatment, achieved regional control and survival rates comparable to CND.

AIM To investigate infused hematopoietic cell doses and their interaction with conditioning regimen intensity +/-total body irradiation (TBI) on outcomes after peripheral blood hematopoietic cell transplant (PBHCT). METHODS Our retrospective cohort included 247 patients receiving a first, T-replete, human leukocyte antigen-matched allogeneic PBHCT and treated between 2001 and 2012. Correlations were calculated using the Pearson product-moment correlation coefficient. Overall survival and progression free survival curves were generated using the Kaplan-Meier method and compared using the log-rank test. RESULTS Neutrophil engraftment was significantly faster after reduced intensity TBI based conditioning [reduced intensity conditioning (RIC) + TBI] and > 4 x 10(6) CD34+ cells/kg infused. A higher total nucleated cell dose led to a higher incidence of grade II-IV acute graft-versus-host disease in the myeloablative + TBI regimen group (P = 0.03), but no significant difference in grade III-IV graft-versus-host disease. A higher total nucleated cell dose was also associated with increased incidence of moderate/severe chronic graft-versus-host disease, regardless of conditioning regimen. Overall and progression-free survival were significantly better in patients with a RIC + TBI regimen and total nucleated cell dose > 8 x 108/kg (3 years, overall survival: 70% vs 38%, P = 0.02, 3 years, progression free survival: 64% vs 38%, P = 0.02). CONCLUSION TBI and conditioning intensity may alter the relationship between infused cell doses and outcomes after PBHCT. Immune cell subsets may predict improved survival after unmanipulated PBHCT.

Objectives: To examine the utility of computed tomography (CT) imaging during routine surveillance for the detection of recurrent head and neck squamous cell carcinoma (HNSCC). Materials/methods: Clinical characteristics of HNSCC patients treated between 2008 and 2017 with radiation therapy or concurrent chemoradiation were abstracted from medical records. In patients who achieved a complete response to treatment by positron emission tomography scan, surveillance CT scans were conducted to the maxillofacial area, neck, and chest every 3 months in year 1, every 6 months in year 2, and every 12 months in years 3 and beyond. Results: Within the entire cohort (n = 534), complete response was achieved in 446 patients (83.5%); of these, 84 (15.7%) patients had a recurrence. Among the 84 patients with disease recurrence, 25 (30%) patients remained alive, of which 15 (18%) underwent successful salvage treatment and became free of disease. Lung screening CT scans detected failure in 8 of these successfully salvaged patients. Among the 8 patients successfully salvaged for locoregional recurrence, 3 failures were asymptomatic at onset and detected by laryngoscope or dental exam. The remaining 5 failures were symptomatic and detected upon work up prompted by symptoms. Maxillofacial and neck surveillance CT imaging failed to detect any successfully salvaged patients. Conclusions: Routine surveillance for HNSCC patients with lung CT imaging had value but routine head and neck CT scans failed to identify any successfully salvaged patients. Given this finding, routine CT imaging surveillance in HNSCC patients should be restricted to annual lung screening with low-dose chest CT.

Objectives: To quantify the effect that time to initiation of treatment after diagnosis has on the outcomes of patients with head and neck squamous cell carcinoma (HNSCC). Methods: This is a single institution retrospective analysis of 633 HNSCC patients treated from 2004 to 2017. Clinical information was abstracted from the medical records. Patients were divided into quartiles based on the time to treatment initiation (0-27 days, 28-41 days, 42-60 days, and > 60 days). Kaplan-Meier overall survival (OS) curves and multivariate cox proportional hazard ratios were determined for time to treatment quartiles. Results: Differences in Kaplan-Meier estimates for OS based on treatment time quartiles were statistically significantly (p = 0.02), and multivariate Cox Proportional hazard ratios for OS revealed that patients in the 42-60 day treatment time group had better OS (hazard ratio = 0.55) compared to patients treated > days after diagnosis (p < 0.01). Conclusions: For our study population, increased time to initiation of treatment did not impact overall survival. These results may help to alleviate patient anxiety while allowing time for useful interventions such as smoking cessation, nutritional counseling, and others that can affect clinical outcomes.

Despite mounting epidemiological evidence suggesting an inverse association between recreational physical activity and cancer risk, evidence associated with head and neck cancer is scant. We conducted a case–control analysis to examine the associations of lifetime physical inactivity with the risk of head and neck squamous cell carcinoma (HNSCC). We utilized data from the Patient Epidemiology Data System at Roswell Park Cancer Institute (RPCI). Participants included 246 patients with HNSCC and 504 cancer-free controls who received medical services at RPCI between 1990 and 1998. Participants were considered physically inactive if they did not participate in any regular, weekly recreational physical activity throughout their lifetime, prior to diagnosis. Multivariate logistic regression models were utilized to estimate odds ratios (OR) and 95% confidence intervals (CI) representing the association between lifetime physical inactivity and HNSCC risk. We observed a significant positive association between recreational physical inactivity and HNSCC risk (OR = 2.73, 95% CI 1.87–3.99, p < 0.001). In subgroup analyses by body mass index (BMI) (underweight/normal-weight: OR = 3.40, 95% CI 1.89–6.12, p < 0.001; overweight/obese: OR = 2.40, 95% CI 1.43–4.02, p < 0.001) and smoking status (former smoker: OR = 3.12, 95% CI 1.89–5.14, p < 0.001; never smoker: OR = 2.71, 95% CI 1.21–6.05, p = 0.020; current smoker: OR = 1.61, 95% CI 0.66–3.95, p = 0.300), significant positive associations were also observed. Results of the current analyses suggest that lifetime physical inactivity associates with HNSCC independent of BMI. In addition, physical inactivity may be a modifiable risk factor among never smokers. These data add to the growing body of evidence suggesting that physical inactivity may be an independent risk factor for cancer.

Objectives/HypothesisTo evaluate subsite-specific differences in survival between squamous cell carcinomas of the base of tongue and tonsillar fossa in a modern cohort likely to have been treated with intensity-modulated radiation therapy, chemotherapy for stage III and IV, and have had a high incidence of human papillomavirus-associated tumors.Study DesignRetrospective cohort analysis utilizing data from the Surveillance, Epidemiology, and End Results program of patients with base of tongue and tonsillar fossa squamous cell carcinoma from 2004 to 2011.MethodsThe cohort included 15,299 primary base of tongue and tonsillar fossa squamous cell carcinoma patients without distant metastases treated between 2004 and 2011. Subsite differences in overall survival and disease-specific survival were examined with Kaplan-Meier curves. Multivariate cox proportional hazard ratios were estimated for overall and disease-specific survival.ResultsThe cohort included 7,220 (47.2%) base of tongue and 8,079 (52.8%) tonsillar fossa squamous cell carcinoma patients. Overall survival with all stages combined favored tonsillar fossa (P < .001) and remained superior when stratified by stage. In multivariate analyses adjusted for age, gender, race, and treatment, the hazard ratio for overall survival was superior for tonsillar fossa tumors compared to base of tongue tumors for all stages (stage 1, P = .041; stage 2, P = .006; stages 3 and 4, P < .001). Disease-specific survival also favored improved outcomes for tonsillar fossa.ConclusionsIn this large modern cohort, overall and disease-specific survival favored outcomes in tonsillar fossa compared with base of tongue. Further study is required to evaluate factors that influence survival differences between tonsillar fossa and base of tongue despite modern therapy.Level of Evidence4 Laryngoscope, 127:1087-1092, 2017

Objective The study evaluated the addition of surgery (S) to radiation (RT) on survival of squamous cell carcinomas (SCC) of tonsillar-fossa (TF) in a modern cohort with similar epidemiology and treatment as current patients. Study Design Retrospective analysis utilizing Surveillance, Epidemiology, and End Results (SEER) Program data. Results For all stages combined TF patients who received S+RT had superior OS (p < 0.01) and DSS (p < 0.01). For each stage OS and DSS was superior for S+RT (p < 0.05). In multivariate analysis, HRs for OS were statistically significantly higher for TF patients (stage 2, 3, and 4) receiving RT alone (p < 0.001). Materials and Methods TF SCC patients treated with either S+RT or RT alone between 2004 and 2011 were examined (n = 6,476). Primary outcome measures included overall survival (OS) and disease specific survival (DSS). Cox proportional hazard ratios (HR) were estimated for patients treated with S+RT compared to RT alone. Conclusions OS and DSS were superior for all stages combined and for stages 2, 3, and 4 in TF patients who received S+RT compared to RT alone.

Objective In this study, we investigated whether physical inactivity was associated with risk of cervical cancer in women treated at an American cancer hospital. Methods This case-control study included 128 patients with cervical cancer and 512 controls matched on age. Controls were women suspected of having but not ultimately diagnosed with a neoplasm. Physical inactivity was defined in accordance with the 2008 Physical Activity Guidelines for Americans. Thus, participants reporting, on average, no moderate or vigorous recreational physical activity were classified as inactive. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Results Compared with noncancer controls, those with cervical cancer had significantly increased odds of reporting abstinence from recreational physical activity (OR, 2.43; 95% CI, 1.56–3.80). No association was noted between occupational-related physical inactivity and cervical cancer (OR, 0.88; 95% CI, 0.58–1.36). Conclusions Our findings suggest that abstinence from regular recreational physical activity is associated with increased odds of cervical cancer. To our knowledge, this is the first US-based study examining these associations. Given the 2008 Physical Activity Guidelines for Americans, this study has identified yet another potential public health benefit to regular physical activity. Further investigation is needed using a larger sample and prospectively collected data to characterize dose of activity to mitigate risk and the optimal window of susceptibility.

OBJECTIVES/HYPOTHESIS:The effect of smoking and human papillomavirus (HPV) on overall survival (OS) of oropharyngeal squamous cell carcinoma (OPSCC) patients undergoing concurrent chemotherapy (CCRT) remains unclear. STUDY DESIGN:Retrospective review. METHODS:Clinical characteristics of OPSCC patients treated between 2008 and 2015 with CCRT were abstracted from medical records. OS curves and multivariate cox proportional hazard ratios (HRs) were examined. RESULTS:Of 120 evaluable patients, 71% had HPV+ tumors. Median follow-up duration for the entire cohort was 41.5 months (range = 6-88 months). HPV+ current smokers experienced significantly worse 5-year OS (73% alive vs. 36% alive, P = .01) and there was a similar trend in HPV- current smokers (66% alive vs. 31% alive, P = .28) compared to former/never smokers undergoing CCRT. In a multivariate cox proportional hazard model adjusted for age, gender, and overall tumor stage, HPV+ current smokers experienced nearly a fourfold increase in overall mortality in comparison to HPV+ never/former smokers (HR = 3.68, 95% CI = 1.35-10.0). Similarly, current smokers with HPV- tumors (HR = 6.80, 95% CI = 1.11-41.67) had increased mortality compared to never/former smokers. CONCLUSIONS:Current smoking is associated with poor prognosis, independent of HPV status, in CCRT-treated OPSCC patients. Current smoking produced an approximately four- to sevenfold increase in risk of mortality for HPV+ and HPV- patients, respectively. Regardless of pack years and HPV status, efforts should be made to achieve smoking cessation before CCRT. LEVEL OF EVIDENCE:4. Laryngoscope, 126:2733-2738, 2016.