Association of Insomnia and Obstructive Sleep Apnea with Worse Oral Mucositis and Quality of Life in Head and Neck Cancer Patients Undergoing Radiation Therapy.

BACKGROUND: Patients with head and neck cancer (HNC) undergoing radiation therapy (RT) often experience sleep disturbances that may contribute to oral mucositis (OM) and quality of life (QOL). METHODS: Patients with HNC treated with RT at a single institution were examined. Sleep questionnaires were given on the first day of RT to assess for insomnia and obstructive sleep apnea (OSA). Patient-reported QOL and oral mucositis were assessed during RT. Associations between insomnia and OSA with QOL were assessed using the Mann-Whitney U test. Linear mixed models assessed associations with OM. RESULTS: Among 87 patients, 34 patients (39%) had subthreshold or greater insomnia and 47 patients (54%) screened positive for OSA. Upon RT completion, patients with subthreshold or greater insomnia had worse physical function (p = 0.005), fatigue (p = 0.01), insomnia (p < 0.001), and sticky saliva (p = 0.002). Patients screening positive for OSA had worse physical function (p = 0.01), sticky saliva (p = 0.02), fatigue (p = 0.007), insomnia (p = 0.009), and pain (p = 0.005). Upon linear mixed model evaluation, subthreshold or greater insomnia (p = 0.01) and positive OSA screen (p = 0.002) were associated with worse OM. CONCLUSION: Insomnia and OSA are highly prevalent in patients with HNC undergoing RT. These sleep disturbances are associated with worse QOL and OM during treatment.

Advancing PROTAC Characterization: Structural Insights through Adducts and Multimodal Tandem-MS Strategies.

Proteolysis targeting chimeras (PROTACs) are specialized molecules that bind to a target protein and a ubiquitin ligase to facilitate protein degradation. Despite their significance, native PROTACs have not undergone tandem mass spectrometry (MS) analysis. To address this gap, we conducted a pioneering investigation on the fragmentation patterns of two PROTACs in development, dBET1 and VZ185. Employing diverse cations (sodium, lithium, and silver) and multiple tandem-MS techniques, we enhanced their structural characterization. Notably, lithium cations facilitated comprehensive positive-mode coverage for dBET1, while negative polarity mode offered richer insights. Employing de novo structure determination on 2DMS data from degradation studies yielded crucial insights. In the case of VZ185, various charge states were observed, with [M + 2H]2+ revealing fewer moieties than [M + H]+ due to charge-related factors. Augmenting structural details through silver adducts suggested both charge-directed and charge-remote fragmentation. This comprehensive investigation identifies frequently dissociated bonds across multiple fragmentation techniques, pinpointing optimal approaches for elucidating PROTAC structures. The findings contribute to advancing our understanding of PROTACs, pivotal for their continued development as promising therapeutic agents.

Skeletal muscle index is associated with long term outcomes after lobectomy for non-small cell lung cancer.

BACKGROUND: Skeletal muscle indices have been associated with improved peri-operative outcomes after surgical resection of non-small-cell lung cancer (NSCLC). However, it is unclear if these indices can predict long term cancer specific outcomes. METHODS: NSCLC patients undergoing lobectomy at our institute between 2009-2015 were included in this analysis (N = 492). Preoperative CT scans were used to quantify skeletal muscle index (SMI) at L4 using sliceOmatic software. Cox proportional modelling was performed for overall (OS) and recurrence free survival (RFS). RESULTS: For all patients, median SMI was 45.7 cm2/m2 (IQR, 40-53.8). SMI was negatively associated with age (R = -0.2; p < 0.05) and positively associated with BMI (R = 0.46; P < 0.05). No association with either OS or RFS was seen with univariate cox modelling. However, multivariable modelling for SMI with patient age, gender, race, smoking status, DLCO and FEV1 (% predicted), American Society of Anesthesiology (ASA) score, tumor histology and stage, and postoperative neoadjuvant therapy showed improved OS (HR = 0.97; P = 0.0005) and RFS (HR = 0.97; P = 0.01) with SMI. Using sex specific median SMI as cutoff, a lower SMI was associated with poor OS (HR = 1.65, P = 0.001) and RFS (HR = 1.47, P = 0.03). CONCLUSIONS: SMI is associated with improved outcomes after resection of NSCLC. Further studies are needed to understand the biological basis of this observation. This study provides additional rationale for designing and implementation of rehabilitation trials after surgical resection, to gain durable oncologic benefit.

Review of fragmentation of synthetic single-stranded oligonucleotides by tandem mass spectrometry from 2014 to 2022.

The fragmentation of oligonucleotides by mass spectrometry allows for the determination of their sequences. It is necessary to understand how oligonucleotides dissociate in the gas phase, which allows interpretation of data to obtain sequence information. Since 2014, a range of fragmentation mechanisms, including a novel internal rearrangement, have been proposed using different ion dissociation techniques. The recent publications have focused on the fragmentation of modified oligonucleotides such as locked nucleic acids, modified nucleobases (methylated, spacer, nebularine and aminopurine) and modification to the carbon 2'-position on the sugar ring; these modified oligonucleotides are of great interest as therapeutics. Comparisons of different dissociation techniques have been reported, including novel approaches such as plasma electron detachment dissociation and radical transfer dissociation. This review covers the period 2014-2022 and details the new knowledge gained with respect to oligonucleotide dissociation using tandem mass spectrometry (without priori sample digestion) during that time, with a specific focus on synthetic single-stranded oligonucleotides.

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.

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.

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.

Advancements in the characterisation of oligonucleotides by high performance liquid chromatography-mass spectrometry in 2021: A short review.

The first oligonucleotide therapeutic was approved by the Food and Drug Administration in 1998, and since then, 12 nucleic acids have been commercialised as medicines. To be approved, the oligonucleotides need to be identified and characterised as well as its related impurities. Different methods exist, but the most commonly used is ion-pairing reversed-phase liquid chromatography with tandem mass spectrometry. The separation obtained depends on the mobile phase and column used. Other methods have been developed, notably by using hydrophilic interaction chromatography and two-dimensional high performance liquid chromatography. Furthermore, ion-pairing reversed-phase high performance liquid chromatography ultra-violet spectroscopy detection and mass spectrometry has been optimised for the analysis of methylated nucleobases due to the utilisation of this modification in the drugs. This review covers the recent advancements in the analysis and characterisation of oligonucleotides in 2021 by high performance liquid chromatography mass spectrometry, notably by hydrophilic interaction chromatography and two-dimensional liquid chromatography but also the different parameters that influence the analysis by ion-pairing reversed-phase high performance liquid chromatography, the characterisation of methylated nucleobases, and the recent software developed for oligonucleotides.

Three-Day Dietary Manipulation in Multiple Sclerosis: Exercise and Fatigue Outcomes.

BACKGROUND: In persons with multiple sclerosis (MS), the effect of nutrition on exercise performance and fatigue remains unknown. The objective was to determine whether a 3-day diet high in triglycerides (FAT) compared with a 3-day diet high in carbohydrates (CARB) would improve fatigue and exercise performance in persons with MS. METHODS: A randomized controlled crossover design was incorporated to study FAT versus CARB on submaximal cycling endurance (60% of peak oxygen consumption), substrate utilization, and fatigue in 12 persons with mild-to-moderate MS (Expanded Disability Status Scale score, 2.0-5.0) and 12 age- and sex-matched controls. RESULTS: There were no differences in cycling time between diets in either group (P = .29). The MS group had no changes in fatigue between diets (P = .64); the control group demonstrated increased total mental fatigue after FAT (P = .05). The control group increased carbohydrate oxidation by 24% at rest and 13% during exercise after CARB. Similarly, the control group significantly increased fat oxidation after FAT by 22% at rest and 68% during exercise (P = .01). These changes were not seen in the MS group. Compared with controls, persons with MS oxidized approximately 50% less fat during exercise after FAT (P = .05). CONCLUSIONS: Neither CARB nor FAT altered submaximal exercise performance or baseline fatigue in the MS group. The results suggest that persons with MS are unable to adapt to dietary changes and oxidize fatty acids as efficiently as controls.

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.

Effects of Preoperative Breathing Exercise on Postoperative Outcomes for Patients With Lung Cancer Undergoing Curative Intent Lung Resection: A Meta-analysis.

OBJECTIVE: To determine the benefits of preoperative breathing exercises on hospital length of stay (LOS), pneumonia, postoperative pulmonary complications (PPC), 6-minute walk distance (6MWD), forced expiratory volume in 1 second (FEV1), and health-related quality of life (HRQOL) in patients undergoing surgical lung cancer resection. DATA SOURCES: PubMed, EMBASE, Web of Science Core Collection, and Cochrane Central Register of Controlled Trials were comprehensively searched from inception to March 2021. STUDY SELECTION: Only studies including preoperative inspiratory muscle training (IMT) and/or breathing exercises compared with a nontraining control group were included. The meta-analysis was done using Cochrane software for multiple variables including LOS, pneumonia, PPC, 6MWD, FEV1, mortality, and HRQOL. DATA EXTRACTION: Two authors extracted the data of the selected studies. The primary outcomes were LOS and PPC. DATA SYNTHESIS: A total of 10 studies were included in this meta-analysis, 8 of which had both IMT and aerobic exercise. Pooled data for patients who performed preoperative breathing exercises, compared with controls, demonstrated a decrease in LOS with a pooled mean difference of -3.44 days (95% confidence interval [CI], -4.14 to -2.75; P<.01). Subgroup analysis also demonstrated that LOS was further reduced when breathing exercises were combined with aerobic exercise (χ2, 4.85; P=.03). Preoperative breathing exercises reduce pneumonia and PPCs with an odds ratio of 0.37 (95% CI, 0.18-0.75; P<.01) and 0.37 (95% CI, 0.21-0.65; P<.01), respectively. An increase in 6MWD of 20.2 meters was noted in those performing breathing exercises (95% CI, 9.12-31.21; P<.01). No significant differences were noted in FEV1, mortality, or HRQOL. CONCLUSIONS: Preoperative breathing exercises reduced LOS, PPC, and pneumonia and potentially improved 6MWD in patients undergoing surgical lung cancer resection. Breathing exercises in combination with aerobic exercise yielded greater reductions in LOS. Randomized controlled trials are needed to test the feasibility of introducing a preoperative breathing exercise program in this patient population.

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.