Association of Pack-Years of Cigarette Smoking With Survival and Tumor Progression Among Patients Treated With Chemoradiation for Head and Neck Cancer.

Importance: After 10 pack-years of smoking was initially established as a threshold for risk stratification, subsequent clinical trials incorporated it to identify candidates for treatment deintensification. However, several recent studies were unable to validate this threshold externally, and the threshold for smoking exposure remains unclear. Objective: To estimate the threshold of pack-years of smoking associated with survival and tumor recurrence among patients with head and neck cancer. Design, Setting, and Participants: This single-institution, cohort study included patients with nonmetastatic head and neck cancer receiving chemoradiation from January 2005 to April 2021. Data were analyzed from January to April 2022. Exposures: Heavy vs light smoking using 22 pack-years as a threshold based on maximizing log-rank test statistic. Main Outcomes and Measures: Overall survival (OS), progression-free survival (PFS), locoregional failure (LRF), and distant failure (DF). Results: A total of 518 patients (427 male [82.4%]; median [IQR] age, 61 [55-66] years) were included. Median (IQR) follow-up was 44.1 (22.3-72.8) months. A nonlinear Cox regression model using restricted cubic splines showed continuous worsening of OS and PFS outcomes as pack-years of smoking increased. The threshold of pack-years to estimate OS and PFS was 22. Cox multivariable analysis (MVA) showed that more than 22 pack-years was associated with worse OS (adjusted hazard ratio [aHR] 1.57; 95% CI, 1.11-2.22; P = .01) and PFS (aHR, 1.38; 95% CI, 1.00-1.89; P = .048). On Fine-Gray MVA, heavy smokers were associated with DF (aHR, 1.71; 95% CI, 1.02-2.88; P = .04), but not LRF (aHR, 1.07; 95% CI, 0.61-1.87; P = .82). When 10 pack-years of smoking were used as a threshold, there was no association for OS (aHR, 1.23; 95% CI, 0.83-1.81; P = .30), PFS (aHR, 1.11; 95% CI, 0.78-1.57; P = .56), LRF (aHR, 1.19; 95% CI, 0.64-2.21; P = .58), and DF (aHR, 1.45; 95% CI, 0.82-2.56; P = .20). Current smoking was associated with worse OS and PFS only among human papillomavirus (HPV)-positive tumors (OS: aHR, 2.81; 95% CI, 1.26-6.29; P = .01; PFS: aHR, 2.51; 95% CI, 1.22-5.14; P = .01). Conclusions and Relevance: In this cohort study of patients treated with definitive chemoradiation, 22 pack-years of smoking was associated with survival and distant metastasis outcomes. Current smoking status was associated with adverse outcomes only among patients with HPV-associated head and neck cancer.

Defining the optimal threshold and prognostic utility of pre-treatment hemoglobin level as a biomarker for survival outcomes in head and neck cancer patients receiving chemoradiation.

OBJECTIVES: We sought to define the optimal threshold for anemia in North American head and neck cancer patients and evaluate its role as a prognostic biomarker. MATERIALS AND METHODS: A single-institution database was queried for patients with head and neck cancer who underwent chemoradiation from January 2005 to April 2021. An optimal threshold of hemoglobin (Hgb) level was defined based on maximum log-rank test statistic. Cox multivariable analysis (MVA), Kaplan-Meier, and propensity score matching were performed to evaluate treatment outcomes. RESULTS: A total of 496 patients were identified. Threshold for Hgb was determined to be 11.4 for both overall survival (OS) and progression-free survival (PFS). Low Hgb was associated with worse OS (adjusted hazards ratio [aHR] 2.41, 95 % confidence interval [CI] 1.53-3.80, p < 0.001) and PFS (aHR 2.01, 95 % CI 1.30-3.11, p = 0.002). Similar findings were observed among 39 matched pairs for OS (5-year OS 22.3 % vs 49.0 %; HR 2.22, 95 % CI 1.23-4.03, p = 0.008) and PFS (5-year PFS 24.3 % vs 39.1 %; HR 1.78, 95 % CI 1.02-3.12, p = 0.04). Among those with HPV-negative tumors, low Hgb was associated with worse OS (aHR 13.90, 95 % CI 4.66-41.44, p < 0.001) and PFS (aHR 5.24, 95 % CI 2.09-13.18, p < 0.001). However, among those with HPV-positive tumors, low Hgb was not associated with both OS (aHR 1.75, 95 % CI 0.60-5.09, p = 0.31) and PFS (aHR 1.13, 95 % CI 0.41-3.14, p = 0.82). CONCLUSION AND RELEVANCE: Low Hgb below 11.4 was an independent adverse prognostic factor for worse survival. It was also prognostic among patients with HPV-negative tumors, but not for HPV-positive tumors.

Effect of musculature on mortality, a retrospective cohort study.

BACKGROUND: While often life-saving, treatment for head and neck cancer (HNC) can be debilitating resulting in unplanned hospitalization. Hospitalizations in cancer patients may disrupt treatment and result in poor outcomes. Pre-treatment muscle quality and quantity ascertained through diagnostic imaging may help identify patients at high risk of poor outcomes early. The primary objective of this study was to determine if pre-treatment musculature was associated with all-cause mortality. METHODS: Patient demographic and clinical characteristics were abstracted from the cancer center electronic database (n = 403). Musculature was ascertained from pre-treatment CT scans. Propensity score matching was utilized to adjust for confounding bias when comparing patients with and without myosteatosis and with and without low muscle mass (LMM). Overall survival (OS) was evaluated using the Kaplan-Meier method and Cox multivariable analysis. RESULTS: A majority of patients were male (81.6%), white (89.6%), with stage IV (41.2%) oropharyngeal cancer (51.1%) treated with definitive radiation and chemotherapy (93.3%). Patients with myosteatosis and those with LMM were more likely to die compared to those with normal musculature (5-yr OS HR 1.55; 95% CI 1.03-2.34; HR 1.58; 95% CI 1.04-2.38). CONCLUSIONS: Musculature at the time of diagnosis was associated with overall mortality. Diagnostic imaging could be utilized to aid in assessing candidates for interventions targeted at maintaining and increasing muscle reserves.

Evaluation of Optimal Threshold of Neutrophil-Lymphocyte Ratio and Its Association With Survival Outcomes Among Patients With Head and Neck Cancer.

Importance: Given the role of inflammation in cancer progression, neutrophil-lymphocyte ratio (NLR) from peripheral blood has been suggested as a readout of systemic inflammation and a prognostic marker in several solid malignant neoplasms. However, optimal threshold for NLR in US patients with head and neck cancer remains unclear. Objective: To evaluate the optimal NLR threshold as a potential prognostic biomarker for survival outcomes. Design, Setting, and Participants: This retrospective cohort study was conducted at a single institution. Participants included 496 patients with nonmetastatic head and neck cancer who underwent chemoradiation from April 2007 to March 2021. Statistical analysis was performed from September to December 2021. Exposures: High vs low NLR. Main Outcomes and Measures: Overall survival (OS) and cancer-specific survival (CSS). Results: A total of 496 patients (411 male patients [82.9%]; 432 White patients [87.1%]; 64 patients with other race or ethnicity [12.9%]; median [IQR] age, 61 [55-67] years) were identified. Median (IQR) follow-up was 44.4 (22.8-74.0) months. Thresholds of NLR for both OS and CSS were 5.71. High NLR above 5.71 was associated with worse OS (adjusted hazard ratio [aHR], 1.97; 95% CI, 1.26-3.09; P = .003) and CSS (aHR, 2.33; 95% CI, 1.38-3.95; P = .002). On logistic multivariable analysis, patients were more likely to have high NLR if they had higher T and N staging (T3-4: aOR, 4.07; 95% CI, 1.92-9.16; P < .001; N2: aOR, 2.97; 95% CI, 1.04-9.17; P = .049; N3: aOR, 11.21; 95% CI, 2.84-46.97; P < .001), but less likely if they had a good performance status (Karnofsky Performance Status 90-100: aOR, 0.29; 95% CI, 0.14-0.59; P < .001). Among 331 patients (66.7%) with available human papillomavirus (HPV) data, high NLR was not associated with OS (HPV-negative: aHR, 2.46; 95% CI, 0.96-6.31; P = .06; HPV-positive: aHR, 1.17; 95% CI, 0.38-3.56; P = .78) and CSS (HPV-negative: aHR, 2.55; 95% CI, 0.81-7.99; P = .11; HPV-positive: aHR, 1.45; 95% CI, 0.44-4.76; P = .54). Conclusions and Relevance: High NLR was associated with worse survival. Patients with substantial disease burden and poor performance status were more likely to have high NLR. These findings suggest that further studies would be warranted to investigate the role of such prognostic marker to identify patients at risk to tailor interventions.

American Cancer Society nutrition and physical activity guideline for cancer survivors.

The overall 5-year relative survival rate for all cancers combined is now 68%, and there are over 16.9 million survivors in the United States. Evidence from laboratory and observational studies suggests that factors such as diet, physical activity, and obesity may affect risk for recurrence and overall survival after a cancer diagnosis. The purpose of this American Cancer Society guideline is to provide evidence-based, cancer-specific recommendations for anthropometric parameters, physical activity, diet, and alcohol intake for reducing recurrence and cancer-specific and overall mortality. The audiences for this guideline are health care providers caring for cancer survivors as well as cancer survivors and their families. The guideline is intended to serve as a resource for informing American Cancer Society programs, health policy, and the media. Sources of evidence that form the basis of this guideline are systematic literature reviews, meta-analyses, pooled analyses of cohort studies, and large randomized clinical trials published since 2012. Recommendations for nutrition and physical activity during cancer treatment, informed by current practice, large cancer care organizations, and reviews of other expert bodies, are also presented. To provide additional context for the guidelines, the authors also include information on the relationship between health-related behaviors and comorbidities, long-term sequelae and patient-reported outcomes, and health disparities, with attention to enabling survivors' ability to adhere to recommendations. Approaches to meet survivors' needs are addressed as well as clinical care coordination and resources for nutrition and physical activity counseling after a cancer diagnosis.

Cross-sectional analysis of myosteatosis and physical function in pretreatment head and neck cancer patients.

BACKGROUND: Head and neck cancer (HNC) and its treatment are associated with muscle weakness and considerable long-term comorbidity. The goal of this study was to determine whether skeletal muscle density (SMD) as quantified from pretreatment computed tomography (CT) scans will correlate with measures of function and strength prior to treatment in physical function in HNC patients. PATIENTS AND METHODS: A cross-sectional analysis was conducted on 90 HNC patients. SMD (myosteatosis vs. normal) was calculated from pretreatment CT scans using SliceOmatic software. Pretreatment physical function was assessed via handgrip strength (HGS), the timed up and go test (TUG), and the short physical performance battery (SPPB). Demographic, cancer, and social characteristics were also collected as confounders. Linear regression models assessed the association between myosteatosis and measures of physical function. RESULTS: The 90 patients were predominately White, male, former smokers with an average BMI of 28.7 ± 5.7 kg/m2. Among men, adjusted models indicate, as compared to those with normal muscle density, the total SPPB score of those with myosteatosis was 1.57 points lower (p = 0.0008), HGS was 0.85 kg lower (p = 0.73), and TUG took 1.34 s longer (p = 0.03). There were no differences in women. CONCLUSION: Myosteatosis is associated with physical function prior to treatment in HNC patients. Larger studies are needed to examine the importance of exercise programs prior to and during treatment to build lean mass and improve long-term prognosis in HNC.

Machine Learning Incorporating Host Factors for Predicting Survival in Head and Neck Squamous Cell Carcinoma Patients.

Prognostication for cancer patients is integral for patient counseling and treatment planning, yet providing accurate prediction can be challenging using existing patient-specific clinical indicators and host factors. In this work, we evaluated common machine learning models in predicting head and neck squamous cell carcinoma (HNSCC) patients' overall survival based on demographic, clinical features and host factors. We found random survival forest had best performance among the models evaluated, which achieved a C-index of 0.729 and AUROC of 0.792 in predicting two-year overall survival. In addition, we verified that host factors are independently predictive of HNSCC overall survival, which improved the C-index by a margin of 0.026 and the AUROC by 0.034. Due to the strong correlation among host factors, we showed that proper dimension reduction is an important step before their incorporation into the machine learning models, which provides a host factor score reflecting the patients' nutrition and inflammation status. The score by itself showed excellent discriminating capacity with the high-risk group having a hazard ratio of 3.76 (1.93-7.32, p < 0.0001) over the low-risk group. The hazard ratios were further improved to 7.41 (3.66-14.98, p < 0.0001) by the random survival forest model after including demographic and clinical features.

A Retrospective Cohort Study of Myosteatosis and Quality of Life in Head and Neck Cancer Patients.

Head and neck cancer (HNC) treatment-related morbidity can be detrimental to quality of life (QOL). Myosteatosis is associated with poor QOL in multiple cancers. If predictive of poor QOL trajectories, myosteatosis would be a tool for clinicians to determine which patients may require additional support during treatment. The purpose of this study was to determine if pretreatment myosteatosis is associated with a poor QOL trajectory following treatment completion. METHODS: In a retrospective cohort design, myosteatosis was determined from pretreatment CT scans. Both physical and global QOL score was assessed through patient interview on follow-up appointment. Demographic, cancer-specific, and social covariates were collected, reported, and considered as potential confounders. RESULTS: The population of 163 patients was mostly male (82.2%) and white (91.4%) with oropharyngeal cancer (55.8%). Males with myosteatosis had a physical QOL score 46.84 points lower at one-year following treatment completion (p = 0.01) than those with normal muscle density (p = 0.01). Males with myosteatosis averaged 57.57 points lower at one-year post-treatment (p = 0.01) in global QOL scores. CONCLUSIONS: Over one year following completion of treatment, patients with myosteatosis reported worse physical and global QOL scores than patients with normal muscle density.

Financial Counseling Is Associated with Reduced Financial Difficulty Scores in Head and Neck Cancer Patients Treated with Radiation Therapy.

BACKGROUND: Financial toxicity (FT) can be devastating to cancer patients, and solutions are urgently needed. We investigated the impact of financial counseling (FC) on FT in head and neck cancer (HNC) patients. METHODS: Via a single-institution database, we reviewed the charts of HNC patients who underwent definitive or post-operative radiotherapy, from October 2013 to December 2020. Of these patients, 387 had provided baseline and post-treatment information regarding financial difficulty. In July 2018, a dedicated financial counselor was provided for radiation therapy patients and we subsequently examined the impact of FC on financial difficulty scores. RESULTS: Following the hiring of a dedicated financial counselor, there was a significant increase in the proportion of patients receiving FC (5.3% vs. 62.7%, p < 0.0001). Compared with baseline scores, patients who did not undergo FC had a significant increase in reported financial difficulty at the end of treatment (p = 0.002). On the other hand, there was no difference in pre- and post-treatment scores in patients who had received FC (p = 0.588). After adjusting for gender and nodal status with a multiple linear regression model, FC was significantly associated with change in financial difficulty (ß = -0.204 ± 0.096, p = 0.035). On average, patients who received FC had a 0.2 units lower change in financial difficulty score as compared with those with the same gender and nodal stage but without FC. CONCLUSIONS: Providing a dedicated financial counselor significantly increased the proportion of HNC receiving FC, resulting in the stabilization of financial difficulty scores post-treatment. Based on a multiple linear regression model, FC was independently associated with reduced financial difficulty. The employment of a financial counselor may be a viable, hospital-based approach to begin to address FT in HNC.

Matched pair analysis for comparison of survival outcome of alternative regimens to standard three-weekly cisplatin-based concurrent chemoradiation of head and neck cancer.

BACKGROUND: To compare head and neck cancer (HNC) patients treated with three-weekly versus weekly cisplatin-based or other chemotherapy-based concurrent chemoradiation (CRT) and CRT with versus without induction chemotherapy (ICT) to investigate differences in overall survival (OS) and cancer-specific survival (CSS). METHODS: HNC patients treated with definitive or adjuvant CRT at Roswell Park Comprehensive Cancer Center between 2003 and 2017 were retrospectively reviewed. Propensity score matching was performed to obtain three sets of balanced matched pairs: three-weekly and weekly cisplatin CRT, three weekly and non-cisplatin CRT, CRT with and without ICT. Multivariate Cox regression and Kaplan-Meier analyses were used to estimate and compare survival outcomes. RESULTS: A total of 623 patients received either definitive (81%) or post-operative (19%) RT. Of these, 283 patients concurrently received three-weekly cisplatin (45%); 189 patients (30%) received weekly cisplatin; 151 patients (24%) received non-cisplatin regimen. Median follow-up was 55.4 months (interquartile range, 38.0-88.7). Patients who received CRT alone and those who received ICT and CRT had no difference in 5-year OS (51.5% and 41.0% respectively, P=0.53) and CSS (64.9% and 49.7% respectively, P=0.21). Compared to patients who received three-weekly cisplatin, patients who received weekly cisplatin had no difference in 5-year OS (59.3% vs. 54.1%, P=0.35) and CSS (70.3% vs. 62.4%, P=0.09); patients who received non-cisplatin CRT also had no difference in 5-year OS (54.5% vs. 58.3%, P=0.51) and CSS (67.5% vs. 64.7%, P=0.45). CONCLUSIONS: No significant difference in OS and CSS was observed in any of the three pairs of CRT regimens. ICT prior to CRT did not improve survival of CRT alone. Non-cisplatin and weekly cisplatin regimens did not prove to be inferior to the standard three-weekly cisplatin.

Matched pair analysis to evaluate weight loss during radiation therapy for head and neck cancer as a prognostic factor for survival.

BACKGROUND: One frequent consequence of radiation therapy (RT) for head and neck cancer (HNC) is weight loss (WL). HNC patients reportedly lose about 9% of their weight during treatment, regardless of pre-treatment WL and nutritional support. We investigated whether high WL during RT has an association with overall (OS) and cancer-specific survival (CSS). METHODS: We retrospectively reviewed weight during RT in HNC patients treated at Roswell Park Comprehensive Cancer Center between 2003 and 2017. High WL was defined as greater than or equal to the median WL. Logistic regression analysis was performed to identify predictors for WL during RT. Multivariate Cox regression and Kaplan-Meier analyses were used to estimate survival outcomes. Propensity score matching was performed to obtain balanced matched-pairs and compare survival outcomes. RESULTS: A total of 843 patients received either definitive (71%) or post-operative (29%) RT. Median follow-up was 53.6 months [interquartile range (IQR) 35.7-88.9]. Median WL was 5.8% (IQR 0.24-10.6) from baseline weight. Patients with high WL had better OS [hazard ratio (HR) 0.75, 95% confidence interval (CI), 0.61-0.93, P=0.01] and CSS (HR 0.71, 95% CI, 0.55-0.93, P=0.01). 258 matched-pairs were analyzed. Median follow-up was 54.8 months (IQR 35.8-90.4). Median OS was 39.2 months (IQR 21.4-75.7) for high WL versus 36.7 months (IQR 14.6-61.7) for low WL cohorts (P=0.047). CONCLUSIONS: Different from previous reports, this study shows that patients with less WL have worse OS. WL during RT may not be a reliable marker for worse prognosis. A better way to evaluate malnutrition in patients undergoing RT is warranted.

A Principal Component of Quality of Life Measures Is Associated with Survival for Head and Neck Cancer Patients Treated with Radiation Therapy.

BACKGROUND: Health-related quality of life (HRQOL) metrics can be associated with survival in head and neck cancer (HNC); however, the impact of HRQOL recovery and the relevant HRQOL domains regarding outcome are unclear. METHODS: Using a single-institution database, we retrospectively reviewed HNC patients treated with definitive or postoperative radiation therapy between 2013 and 2018. The recovery of individual HRQOL domains were determined by the ratio of the post-treatment to baseline scores. Univariate and Multivariate Cox regression were used to analyze survival outcomes. Principal component analysis was used to adjust for multicollinearity of HRQOL domains. RESULTS: In 218 HNC patients who received radiation therapy, median follow-up was 24.8 months (interquartile range (IQR) 14.5-32.0). Principal component analysis evaluating the recovery of HRQOL domains revealed two independent principal components (PC), PC1 and PC2. PC1, which received contributions from the functional domains; physical (PF), role (RF), emotional (EF), cognitive (CF), and global health status (GQOL) was significantly associated with disease-free (HR = 0.77, 95% CI 0.61-0.98, p = 0.034) and overall survival (HR = 0.76, 95% CI 0.65-0.91, p = 0.004) on multivariate analysis and PC2, had no correlation with outcome and was mainly represented by social functioning. Unplanned hospitalization was significantly associated with lower PC1 scores (ß = -0.997, Std. Error = 0.244, p < 0.001). CONCLUSION: Our study provides evidence that post-treatment recovery of HRQOL domains were associated with overall survival (OS) in HNC. PC1 is an attractive clinical tool to assess the recovery across multiple different HRQOL and the relationship with survival. Future prospective studies may identify patients who could benefit from additional rehabilitation based on PC1 score.

Change in Physical Performance Correlates with Decline in Quality of Life and Frailty Status in Head and Neck Cancer Patients Undergoing Radiation with and without Chemotherapy.

Patient-reported quality of life (QoL) metrics, frailty status, and physical functioning are emerging concepts in head and neck cancer (HNC) with implications on both treatment decision-making and prognosis. The impact of treatment-related functional decline on QoL and frailty has not been well-characterized in HNC and was the focus of this investigation. METHODS: Patients who underwent radiation therapy for HNC from 2018 to 2020 were evaluated as a prospective observational cohort. Functional decline, QoL, and the frailty phenotype were measured via the Short Physical Performance Battery (SPPB), European Organization for Research and Treatment of Cancer (EORTC) qlq-C30, and Fried Frailty index, respectively. RESULTS: A total of 106 HNC patients were included, 75 of which received concurrent chemoradiation therapy (CCRT) and 31 received radiation alone, both with and without surgery. There was a decrease in SPPB overall (p < 0.001) from the beginning to the end of treatment in the CCRT group but not the radiation group (p = 0.43). Change in overall SPPB points following treatment correlated with the decline in physical QoL for both groups (p < 0.05) as well as transition frail status in the CCRT group (p < 0.001) with a trend in the radiation group (p = 0.08). CONCLUSIONS: Change in SPPB correlates with QoL and transition to frailty status in patients undergoing definitive CCRT for HNC with similar trends in those receiving radiation alone. Decline in SPPB could potentially be useful in identification of those who may benefit from rehabilitation in future studies.

Association of significant financial burden with survival for head and neck cancer patients treated with radiation therapy.

OBJECTIVE: To assess the association between financial toxicity and survival in patients with head and neck cancer (HNC). MATERIALS AND METHODS: Using a single-institution database, we retrospectively reviewed HNC patients treated at Roswell Park Comprehensive Cancer Center treated with definitive or postoperative radiation therapy between 2013 and 2017. Kaplan-Meier method and log-rank tests were used to analyze survival outcomes. Propensity score matching on all clinically relevant baseline characteristics was performed to address selection bias. All statistical tests were two-sided and those less than 0.05 were considered statistically significant. RESULTS: Of a total of 284 HNC patients (age: median 61 years, IQR 55-67; 220 [77.5%] men), 204 patients (71.8%) received definitive radiation and 80 patients (28.2%) received adjuvant radiation. There were 41 patients (14.4%) who reported high baseline financial toxicity. Chemotherapy was used in 237 patients (83.5%). On multivariable analysis, those with high financial toxicity exhibited worse overall survival (hazards ratio [HR] 1.75, 95% confidence interval [CI] 1.05-2.94, p = 0.03) and cancer specific survival (HR 2.28, 95% CI 1.31-3.96, p = 0.003). On matched pair analysis of 66 patients, high financial toxicity remained associated with worse OS (HR 2.72, 95% CI 1.04-7.09, p = 0.04) and CSS (HR 3.75, 95% CI 1.22-11.5, p = 0.02). CONCLUSION: HNC patient reported baseline financial toxicity was significantly correlated with both decreased overall and cancer specific survival. These significant correlations held after match pairing. Further research is warranted to investigate the impact of financial toxicity in HNC and mitigate its risk.

Associations Between Polymorphisms in Genes Related to Oxidative Stress and DNA Repair, Interactions With Serum Antioxidants, and Prostate Cancer Risk: Results From the Prostate Cancer Prevention Trial.

Study of polymorphisms in genes related to the generation and removal of oxidative stress and repair of oxidative DNA damage will lead to new insights into the genetic basis of prostate cancer. In the Prostate Cancer Prevention Trial (PCPT), a double-blind, randomized controlled trial testing finasteride versus placebo for prostate cancer prevention, we intend to investigate the role of oxidative stress/DNA repair mechanisms in prostate cancer etiology and whether these polymorphisms modify prostate cancer risk by interacting with antioxidant status in both placebo and finasteride arms. We evaluated associations of selected candidate polymorphisms in genes in these pathways, and interactions with pre-diagnostic serum antioxidants, and the risk of prostate cancer among 1,598 cases and 1,706 frequency-matched controls enrolled in the PCPT. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable-adjusted logistic regression models. While there were no statistically significant associations observed in the placebo arm, several SNPs were associated with prostate cancer in the finasteride arm. Specifically, APEX1-rs1760944 was associated with increased risk of total prostate cancer (per minor allele: p-trend=0.04). OGG1-rs1052133 was positively (CG/GG vs. CC: OR=1.32, 95% CI: 1.01-1.73) and NOS3-rs1799983 was inversely (per minor allele: p-trend=0.04) associated with risk of low-grade prostate cancer. LIG3-rs1052536 and XRCC1-rs25489 were suggestively associated with reduced risk of high-grade prostate cancer (per minor allele: both p-trend=0.04). In the placebo arm, significant associations were observed among men with higher serum lycopene for APEX1-rs1760944 and NQO1-rs1800566, or higher serum ß-cryptoxanthin for ERCC4-rs1800067. In the finasteride arm, stronger associations were observed among men with lower serum lycopene for NOS3-rs1799983, higher serum α-carotene, ß-carotene, and ß-cryptoxanthin for LIG3-rs1052536, or lower serum retinol for SOD2-rs1799725. These results suggest that germline variations in oxidative stress and DNA repair pathways may contribute to prostate carcinogenesis and that these associations may differ by intraprostatic sex steroid hormone status and be further modified by antioxidant status. Findings provide insights into the complex role of gene, gene-antioxidant and -finasteride interactions in prostate cancer etiology, and thus may lead to the development of preventative strategies.

Matched pair analysis to evaluate the impact of hospitalization during radiation therapy as an early marker of survival in head and neck cancer patients.

BACKGROUND: Complications from radiotherapy (RT) alone or combined with surgery and/or chemotherapy for head and neck cancer (HNC) sometimes necessitate hospitalization. Our aim was to evaluate the frequency, cause, and survival outcomes associated with hospitalizations in patients undergoing RT for HNC. PATIENTS AND METHODS: Using a retrospective single-institution database, we reviewed hospitalization records of HNC patients treated at Roswell Park Comprehensive Cancer Center with definitive or post-operative RT between 2003 and 2017. Patients who were admitted during treatment and within 90-days post-RT were identified. Multivariate analyses, Kaplan-Meier statistics, and analysis on propensity score matching were performed to obtain matched-pair, after matching baseline characteristics, such as age, gender, smoking, tumor staging, p16 status, and treatments received. RESULTS: 839 patients were eligible for analysis. Median follow-up was 34.8 months (Interquartile range [IQR] 15.6-64.8). 595 (71%) received definitive RT and 244 (29%) received adjuvant RT. Chemotherapy was used in 671 patients (80%). 171 patients (20%) had at least one hospitalization. Dehydration (40%) and fever (29%) were the most frequent causes of admission. Hospitalized patients had significantly worse overall survival (OS) (Hazards ratio [HR] 1.61, 95% CI 1.26-2.07, p < 0.001) and cancer-specific survival (CSS) (HR 1.45, 95% CI 1.07-1.95, p = 0.02). 163 matched pairs had median follow-up of 58.6 months (IQR 37.6-85.0). Median OS was 34.5 months (IQR 13.3-58.0) for hospitalized versus 44.2 months (IQR 20.3-78.7) for non-hospitalized patients (p = 0.01). CONCLUSION: This study reveals significantly worse OS and CSS for patients hospitalized during RT for HNC. Hospitalization may be an early marker for worse survival.

Evaluation of radiation treatment volumes for unknown primaries of the head and neck in the era of FDG PET.

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.

Daily Time of Radiation Treatment Is Associated with Subsequent Oral Mucositis Severity during Radiotherapy in Head and Neck Cancer Patients.

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.

Inadequate Nutrition Coverage in Outpatient Cancer Centers: Results of a National Survey.

Cancer-related malnutrition is associated with poor health outcomes, including decreased tolerance to cancer therapy, greater treatment toxicities, and increased mortality. Medical nutrition therapy (MNT) optimizes clinical outcomes, yet registered dietitian nutritionists (RDNs), the healthcare professionals specifically trained in MNT, are not routinely employed in outpatient cancer centers where over 90% of all cancer patients are treated. The objective of this study was to evaluate RDN staffing patterns, nutrition services provided in ambulatory oncology settings, malnutrition screening practices, and referral and reimbursement practices across the nation in outpatient cancer centers. An online questionnaire was developed by the Oncology Nutrition Dietetic Practice Group (ON DPG) of the Academy of Nutrition and Dietetics and distributed via the ON DPG electronic mailing list. Complete data were summarized for 215 cancer centers. The mean RDN full-time equivalent (FTE) for all centers was 1.7 ± 2.0. After stratifying by type of center, National Cancer Institute-Designated Cancer Centers (NCI CCs) employed a mean of 3.1 ± 3.0 RDN FTEs compared to 1.3 ± 1.4 amongst non-NCI CCs. The RDN-to-patient ratio, based on reported analytic cases, was 1 : 2,308. Per day, RDNs evaluated and counseled an average of 7.4 ± 4.3 oncology patients. Approximately half (53.1%) of the centers screened for malnutrition, and 64.9% of these facilities used a validated malnutrition screening tool. The majority (76.8%) of centers do not bill for nutrition services. This is the first national study to evaluate RDN staffing patterns, provider-to-patient ratios, and reimbursement practices in outpatient cancer centers. These data indicate there is a significant gap in RDN access for oncology patients in need of nutritional care.

Small form factor, flexible, dual-modality handheld probe for smartphone-based, point-of-care oral and oropharyngeal cancer screening.

Oral cancer is a growing health issue in low- and middle-income countries due to betel quid, tobacco, and alcohol use and in younger populations of middle- and high-income communities due to the prevalence of human papillomavirus. The described point-of-care, smartphone-based intraoral probe enables autofluorescence imaging and polarized white light imaging in a compact geometry through the use of a USB-connected camera module. The small size and flexible imaging head improves on previous intraoral probe designs and allows imaging the cheek pockets, tonsils, and base of tongue, the areas of greatest risk for both causes of oral cancer. Cloud-based remote specialist and convolutional neural network clinical diagnosis allow for both remote community and home use. The device is characterized and preliminary field-testing data are shared.