Association of low adherence to weekly cisplatin with outcomes in patients with head and neck squamous cell carcinoma: a retrospective cohort study.

BACKGROUND: The National Comprehensive Cancer Network (NCCN) guideline recommends consideration of weekly cisplatin as an alternative option for patients with head and neck cancer undergoing definitive chemoradiation. However, in a recent phase III trial (ConCERT), 20% of patients treated with weekly cisplatin could not receive a total of 200 mg/m2, and the association of low adherence to weekly cisplatin and cancer control outcomes remains unclear. To fill this knowledge gap, we performed an observational cohort study of patients with head and neck cancer undergoing definitive chemoradiation with weekly cisplatin. METHODS: Our institutional database was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation with weekly cisplatin (40 mg/m2) between November 2007 and April 2023. Adherence to weekly cisplatin was defined as receiving at least 5 cycles with a total cumulative dose of 200 mg/m2. Survival outcomes were evaluated using Kaplan-Meier method, log-rank tests, Cox proportional hazard multivariable (MVA) analyses. Logistic MVA was performed to identify variables associated with low adherence to weekly cisplatin. Fine-Gray MVA was performed to analyze failure outcomes with death as a competing event. RESULTS: Among 119 patients who met our criteria, 51 patients (42.9%) had low adherence to weekly cisplatin. Median follow up was 19.8 months (interquartile range 8.8-65.6). Low adherence to weekly cisplatin was associated with worse overall survival (adjusted hazards ratio [aHR] 2.94, 95% confidence interval [CI] 1.58-5.47, p < 0.001) and progression-free survival (aHR 2.32, 95% CI 1.29-4.17, p = 0.005). It was also associated with worse distant failure (aHR 4.55, 95% CI 1.19-17.3, p = 0.03), but not locoregional failure (aHR 1.61, 95% CI 0.46-5.58, p = 0.46). KPS < 90 was the only variable associated with low adherence to weekly cisplatin (adjusted odds ratio [aOR] 2.67, 95% CI 1.10-6.65, p = 0.03). CONCLUSION: Our study suggested that over 40% of patients underwent fewer than 5 weekly cisplatin cycles and that low adherence to weekly cisplatin was an independent, adverse prognostic factor for worse survival and distant failure outcomes. Those with reduced adherence to weekly cisplatin were more likely to have poor performance status. Further studies are warranted to improve the adherence to chemotherapy and outcomes.

Association of pre-treatment lymphocyte-monocyte ratio with survival outcome in patients with head and neck cancer treated with chemoradiation.

BACKGROUND: Given the role of systematic inflammation in cancer progression, lymphocyte-monocyte ratio (LMR) from peripheral blood has been suggested as a biomarker to assess the extent of inflammation in several solid malignancies. However, the role of LMR as a prognostic factor in head and neck cancer was unclear in several meta-analyses, and there is a paucity of literature including patients in North America. We performed an observational cohort study to evaluate the association of LMR with survival outcomes in North American patients with head and neck cancer. METHODS: A single-institution, retrospective database was queried for patients with non-metastatic head and neck cancer who underwent definitive chemoradiation from June 2007 to April 2021 at the Roswell Park Comprehensive Cancer Center. Primary endpoints were overall survival (OS) and cancer-specific survival (CSS). The association of LMR with OS and CSS was examined using nonlinear Cox proportional hazard model using restricted cubic splines (RCS). Cox multivariable analysis (MVA) and Kaplan-Meier method were used to analyze OS and CSS. Pre-radiation LMR was then stratified into high and low based on its median value. Propensity scored matching was used to reduce the selection bias. RESULTS: A total of 476 patients met our criteria. Median follow up was 45.3 months (interquartile range 22.8-74.0). The nonlinear Cox regression model showed that low LMR was associated with worse OS and CSS in a continuous fashion without plateau for both OS and CSS. On Cox MVA, higher LMR as a continuous variable was associated with improved OS (adjusted hazard ratio [aHR] 0,90, 95% confidence interval [CI] 0.82-0.99, p = 0.03) and CSS (aHR 0.83, 95% CI 0.72-0.95, p = 0.009). The median value of LMR was 3.8. After propensity score matching, a total of 186 pairs were matched. Lower LMR than 3.8 remained to be associated with worse OS (HR 1.59, 95% CI 1.12-2.26, p = 0.009) and CSS (HR 1.68, 95% CI 1.08-2.63, p = 0.02). CONCLUSION: Low LMR, both as a continuous variable and dichotomized variable, was associated with worse OS and CSS. Further studies would be warranted to evaluate the role of such prognostic marker to tailor interventions.

Occurrence and Characterization of Steroid Growth Promoters Associated with Particulate Matter Originating from Beef Cattle Feedyards.

Studies of steroid growth promoters from beef cattle feedyards have previously focused on effluent or surface runoff as the primary route of transport from animal feeding operations. There is potential for steroid transport via fugitive airborne particulate matter (PM) from cattle feedyards; therefore, the objective of this study was to characterize the occurrence and concentration of steroid growth promoters in PM from feedyards. Air sampling was conducted at commercial feedyards (n = 5) across the Southern Great Plains from 2010 to 2012. Total suspended particulates (TSP), PM10, and PM2.5 were collected for particle size analysis and steroid growth promoter analysis. Particle size distributions were generated from TSP samples only, while steroid analysis was conducted on extracts of PM samples using liquid chromatography mass spectrometry. Of seven targeted steroids, 17α-estradiol and estrone were the most commonly detected, identified in over 94% of samples at median concentrations of 20.6 and 10.8 ng/g, respectively. Melengestrol acetate and 17α-trenbolone were detected in 31% and 39% of all PM samples at median concentrations of 1.3 and 1.9 ng/g, respectively. Results demonstrate PM is a viable route of steroid transportation and may be a significant contributor to environmental steroid hormone loading from cattle feedyards.

Establishment, characterization, and toxicological application of loggerhead sea turtle (Caretta caretta) primary skin fibroblast cell cultures.

Pollution is a well-known threat to sea turtles but its impact is poorly understood. In vitro toxicity testing presents a promising avenue to assess and monitor the effects of environmental pollutants in these animals within the legal constraints of their endangered status. Reptilian cell cultures are rare and, in sea turtles, largely derived from animals affected by tumors. Here we describe the full characterization of primary skin fibroblast cell cultures derived from biopsies of multiple healthy loggerhead sea turtles (Caretta caretta), and the subsequent optimization of traditional in vitro toxicity assays to reptilian cells. Characterization included validating fibroblast cells by morphology and immunocytochemistry, and optimizing culture conditions by use of growth curve assays with a fractional factorial experimental design. Two cell viability assays, MTT and lactate dehydrogenase (LDH), and an assay measuring cytochrome P4501A (CYP1A) expression by quantitative PCR were optimized in the characterized cells. MTT and LDH assays confirmed cytotoxicity of perfluorooctanoic acid at 500 µM following 72 and 96 h exposures while CYP1A5 induction was detected after 72 h exposure to 0.1-10 µM benzo[a]pyrene. This research demonstrates the validity of in vitro toxicity testing in sea turtles and highlights the need to optimize mammalian assays to reptilian cells.

Association of Body Mass Index With Outcomes Among Patients With Head and Neck Cancer Treated With Chemoradiotherapy.

Importance: Combined modality therapy, such as chemoradiotherapy, often results in significant morbidity among patients with head and neck cancer. Although the role of body mass index (BMI) varies based on cancer subtypes, its association with treatment response, tumor recurrence, and survival outcomes among patients with head and neck cancer remains unclear. Objective: To evaluate the role of BMI in treatment response, tumor recurrence, and survival outcomes among patients with head and neck cancer undergoing chemoradiotherapy. Design, Setting, and Participants: This retrospective, observational, single-institution cohort study conducted at a comprehensive cancer center included 445 patients with nonmetastatic head and neck cancer who underwent chemoradiotherapy from January 1, 2005, to January 31, 2021. Exposure: Normal vs overweight or obese BMI. Main Outcomes and Measures: Metabolic response after chemoradiotherapy, locoregional failure (LRF), distant failure (DF), overall survival (OS), and progression-free survival (PFS), with Bonferroni correction used to adjust for multiple comparisons and P < .025 being considered statistically significant. Results: A total of 445 patients (373 men [83.8%]; median age, 61 years [IQR, 55-66 years]; 107 [24.0%] with normal BMI, 179 [40.2%] with overweight BMI, and 159 [35.7%] with obese BMI) were included for analysis. Median follow-up was 48.1 months (IQR, 24.7-74.9 months). On Cox proportional hazards regression multivariable analysis, only overweight BMI was associated with improved OS (5-year OS, 71.5% vs 58.4%; adjusted hazard ratio [AHR], 0.59 [95% CI, 0.39-0.91]; P = .02) and PFS (5-year PFS, 68.3% vs 50.8%; AHR, 0.51 [95% CI, 0.34-0.75]; P < .001). On logistic multivariable analysis, overweight BMI (91.6% vs 73.8%; adjusted odds ratio [AOR], 0.86 [95% CI, 0.80-0.93]; P < .001) and obese BMI (90.6% vs 73.8%; AOR, 0.89 [95% CI, 0.81-0.96]; P = .005) were associated with complete metabolic response on follow-up positron emission tomography-computed tomography after treatments. On Fine-Gray multivariable analysis, overweight BMI was associated with reduction in LRF (5-year LRF, 7.0% vs 25.9%; AHR, 0.30 [95% CI, 0.12-0.71]; P = .01), but not DF (5-year DF, 17.4% vs 21.5%; AHR, 0.92 [95% CI, 0.47-1.77]; P = .79). Obese BMI was not associated with LRF (5-year LRF, 10.4% vs 25.9%; AHR, 0.63 [95% CI, 0.29-1.37]; P = .24) or DF (5-year DF, 15.0% vs 21.5%; AHR, 0.70 [95% CI, 0.35-1.38]; P = .30). Conclusion: In this cohort study of patients with head and neck cancer, when compared with normal BMI, overweight BMI was an independent factor favorably associated with complete response after treatments, OS, PFS, and LRF. Further investigations are warranted to improve understanding on the role of BMI among patients with head and neck cancer.

Postoperative Restrictive Opioid Protocols and Durable Changes in Opioid Prescribing and Chronic Opioid Use.

Importance: Changes in postsurgical opioid prescribing practices may help reduce chronic opioid use in surgical patients. Objective: To investigate whether postsurgical acute pain across different surgical subspecialties can be managed effectively after hospital discharge with an opioid supply of 3 or fewer days and whether this reduction in prescribed opioids is associated with reduced new, persistent opioid use. Design, Setting, and Participants: In this prospective cohort study with a case-control design, a restrictive opioid prescription protocol (ROPP) specifying an opioid supply of 3 or fewer days after discharge from surgery along with standardized patient education was implemented across all surgical services at a tertiary-care comprehensive cancer center. Participants were all patients who underwent surgery from August 1, 2018, to July 31, 2019. Main Outcomes and Measures: Main outcomes were the rate of compliance with the ROPP in each surgical service, the mean number of prescription days and refill requests, type of opioid prescribed, and rate of conversion to chronic opioid use determined via a state-run opioid prescription program. Postsurgical complications were also measured. Results: A total of 4068 patients (mean [SD] age, 61.0 [13.8] years; 2528 women [62.1%]) were included, with 2017 in the pre-ROPP group (August 1, 2018, to January 31, 2019) and 2051 in the post-ROPP group (February 1, 2019, to July 31, 2019). The rate of compliance with the protocol was 95%. After implementation of the ROPP, mean opioid prescription days decreased from a mean (SD) of 3.9 (4.5) days in the pre-ROPP group to 1.9 (3.6) days in the post-ROPP group (P < .001). The ROPP implementation led to a 45% decrease in prescribed opioids after surgery (mean [SD], 157.22 [338.06] mean morphine milligram equivalents [MME] before ROPP vs 83.54 [395.70] MME after ROPP; P < .001). Patients in the post-ROPP cohort requested fewer refills (367 of 2051 [17.9%] vs 422 of 2017 [20.9%] in the pre-ROPP cohort; P = .02). There was no statistically significant difference in surgical complications. The conversion rate to chronic opioid use decreased following ROPP implementation among both opioid-naive patients with cancer (11.3% [143 of 1267] to 4.5% [118 of 2645]; P < .001) and those without cancer (6.1% [19 of 310] to 2.7% [16 of 600]; P = .02). Conclusions and Relevance: In this cohort study, prescribing an opioid supply of 3 or fewer days to surgical patients after hospital discharge was feasible for most patients, led to a significant decrease in the number of opioids prescribed after surgery, and was associated with a significantly decreased conversion to long-term opioid use without concomitant increases in refill requests or significant compromises in surgical recovery.

Inflammatory myofibroblastic tumor of the mesentery: a clinical dilemma.

Although rare, extra-pulmonary inflammatory myofibroblastic tumors (IMTs) are becoming increasingly recognized. While surgical resection is currently an effective and accepted treatment for IMTs, the optimal management of unresectable or residual IMTs remains a clinical dilemma. We present the case of an incompletely resected IMT treated successfully with anti-inflammatory therapy alone, and describe the rationale for this approach.

Embryotoxicity of Corexit 9500 in mallard ducks (Anas platyrhynchos).

Embryotoxicity of the oil dispersant Corexit 9500 was examined using fertilized mallard duck eggs. Corexit 9500 was topically applied below the air cell to eggs in volumes ranging from 0 to 100 µL on day 3 of incubation. The highest incidence of mortality occurred at developmental stage 4, one day post-Corexit 9500 application. Hatching success was significantly decreased among eggs treated with ≥ 20 µL of Corexit 9500 as compared to controls (P ≤ 0.047). No egg treated with ≥ 40 µL successfully hatched. The application volume resulting in 50% mortality (corrected for control survival) was determined to be 15.5 µL. Developmental stage at embryo death was also significantly decreased compared to controls in eggs exposed to 40 µL (P = 0.0042) and above.

Laparoscopic diagnosis of magnetic malrotation with fistula and volvulus.

INTRODUCTION: Most foreign bodies that a child ingests pass harmlessly through the gastrointestinal tract. However, ingesting multiple magnets places a child at risk for serious viscus injury. CASE DESCRIPTION: A 16-y-old boy swallowed multiple magnets and presented with abdominal pain and emesis. Upon laparoscopy, the boy was found to have malrotation with volvulus caused by a cecal magnet attracted to a gastric magnet, resulting in a gastrocecal fistula. DISCUSSION: We review the management of magnet ingestion with an emphasis on a high index of suspicion and the use of laparoscopy for diagnosis, as well as the consequences of a coexisting rotational anomaly.

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.

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.

Role of Repeat PET/CT Imaging in Head and Neck Cancer Following Initial Incomplete PET/CT Response to Chemoradiation.

Despite waiting 13 weeks to perform a PET/CT scan after completion of chemoradiation for head and neck squamous cell carcinoma (HNSCC), equivocal findings are often found that make assessing treatment response difficult. This retrospective study examines the utility of a repeat PET/CT scan in HNSCC patients following an incomplete response on initial post-treatment imaging. For this cohort of 350 patients, initial PET/CT was performed 13 weeks after completion of treatment. For select patients with an incomplete response, repeat PET/CT was performed a median of 91 days later. Primary endpoints were conversion rate to complete response (CR) and the predictive values of repeat PET/CT imaging. Of 179 patients who did not have an initial complete response, 57 (32%) received a repeat PET/CT scan. Among these patients, 26 of 57 (48%) had a CR on repeat PET/CT. In patients with CR conversion, there were no cases of disease relapse. The sensitivity, specificity, PPV, and NPV for the repeat PET/CT for locoregional disease were 100%, 59%, 42%, and 100%. Repeat PET/CT in HNSCC patients with an incomplete post-treatment scan can be valuable in obtaining diagnostic clarity. This can reduce the incidence of unnecessary biopsies and neck dissections.

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.

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.

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.

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.

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.

Managing the Oral Health of Cancer Patients During the COVID-19 Pandemic: Perspective of a Dental Clinic in a Cancer Center.

The practice of dentistry has been dramatically altered by the coronavirus disease 2019 (COVID-19) pandemic. Given the close person-to-person contact involved in delivering dental care and treatment procedures that produce aerosols, dental healthcare professionals including dentists, dental assistants and dental hygienists are at high risk of exposure. As a dental clinic in a comprehensive cancer center, we have continued to safely provide medically necessary and urgent/emergent dental care to ensure that patients can adhere to their planned cancer treatment. This was accomplished through timely adaptation of clinical workflows and implementation of practice modification measures in compliance with state, national and federal guidelines to ensure that risk of transmission remained low and the health of both immunocompromised cancer patients and clinical staff remained protected. In this narrative review, we share our experience and measures that were implemented in our clinic to ensure that the oral health needs of cancer patients were met in a timely manner and in a safe environment. Given that the pandemic is still on-going, the impact of our modified oral healthcare delivery model in cancer patients warrants continued monitoring and assessment.