The prognostic impact of daytime and seasonality of radiotherapy on head and neck cancer.

BACKGROUND: The potential impact of daytime and season of radiotherapy application on prognosis is unclear. This was analyzed in a retrospective cohort of patients who were diagnosed with non-metastatic head and neck squamous cell carcinoma (HNSCC) and treated with definitive radiotherapy with or without chemotherapy. MATERIALS AND METHODS: Patient and tumor characteristics, treatment parameters and outcome until last follow-up or death were obtained. Median radiotherapy delivery daytime of each patient was categorized as morning (AM) and afternoon (PM). Treatment season was defined by median date of treatment course. Each year was divided into DARK and LIGHT according to equinoxes. Time-to-event endpoints were defined by first biopsy confirming the HNSCC. RESULTS: Six hundred fifty-five cases were identified who were treated with (chemo)radiotherapy between 2002 and 2015. Median follow-up was 47 months. No significant heterogeneity in patient, tumor and treatment characteristics were observed between DARK and LIGHT or regarding median daily fraction time (X2 p > 0.05). Five-year loco-regional control (73% vs. 61%; p = 0.0108) and progression-free survival (51% vs. 43%; p = 0.0374) were superior when radiotherapy was administered in DARK. Neither the daytime nor any other treatment time-related parameter affected prognosis. CONCLUSION: This is the first study investigating and presenting the prognostic impact of seasonality regarding the treatment course on loco-regional control and progression-free survival (DARK > LIGHT). The biological mechanism of action is unclear. These results should be interpreted with caution and our findings have to be validated externally.

The impact of delivery daytime and seasonality of radiotherapy for head and neck cancer on toxicity burden.

AIM: The potential impact of the daytime and season of radiotherapy application on acute and late toxicity burden was analyzed on a cohort of curatively treated head and neck squamous cell carcinoma patients. METHODS: Through a retrospective chart review, patient and tumor characteristics, treatment parameters and outcome were obtained. Patients treated with definitive or adjuvant radiotherapy with and without chemotherapy receiving ≥60 Gy between 2002 and 2015 were included (n = 617). Daily fraction times and dates were extracted. Median radiotherapy delivery time of each patient was categorized as morning (AM) and afternoon (PM). Treatment season was defined by the median day of the treatment course. Each year was divided into DARK and LIGHT by the March and September equinoxes. Acute (T) and late (A) toxicity were defined by TAME methodology. RESULTS: Median follow-up was 51 months. Mean T and A scores during and after radiotherapy in DARK vs. LIGHT were 1.98 vs. 1.61 (p = 0.0127) and 0.41 vs. 0.30 (p = 0.1699), respectively. Mean T and A scores during and after AM vs. PM radiotherapy were 1.71 vs. 1.88 (p = 0.0387) and 0.31 vs. 0.41 (p = 0.2638), respectively. Multivariate analyses indicated DARK vs. LIGHT as the only independent treatment time-related factor among other factors such as tumor subsite, UICC stage, radiotherapy technique, and chemotherapy for T. CONCLUSION: This is the first study investigating the impact of seasonality on toxicity burden, showing higher acute toxicity with radiotherapy in DARK. The daytime did not predict the toxicity. The hypothesis-generating findings of this retrospective study should be further investigated.

Effect of preoperative immunonutrition on complications after salvage surgery in head and neck cancer.

BACKGROUND: Patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma are at high risk of postoperative complications due to the adverse effects of radiotherapy on wound healing. Malnutrition is an additional risk factor and we tested the hypothesis that preoperative administration of immunonutrition would decrease complications in this high risk population. METHODS: This single armed study with historical control included consecutive patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma. We compared outcomes before and after implementation of preoperative immunonutrition and adjusted the regression analysis for gender, age, body mass index, Nutritional Risk Screening (NRS 2002), tobacco and alcohol consumption, tumor localization, tumor stage, and type of surgery. The primary endpoint was overall complications from surgery within a follow-up of 30 days. RESULTS: Ninety-six patients were included (intervention group: 51, control group: 45). Use of preoperative immunonutrition was associated with a significant reduction in overall complications (35% vs. 58%, fully-adjusted odds ratio 0.30 (95%CI 0.10-0.91, p = 0.034). Length of hospital stay was also significantly reduced (17 days vs. 6 days, p = < 0.001). No differences in mortality and hospital readmission were found. These results remained robust in multivariate analysis. CONCLUSIONS: In patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma, preoperative immunonutrition exhibited favorable effects on the complication rate and consequently reduced the length of hospital stay. By improving both tissue regeneration and immune response, immunonutrition may help to improve surgical outcomes in this high-risk population.

Comparison of contemporary staging systems for oropharynx cancer in a surgically treated multi-institutional cohort.

BACKGROUND: Between the publication of the Union of International Cancer Control staging system (UICC) 7th and 8th editions, other staging algorithms for oropharyngeal squamous cell carcinoma (OPSCC) were proposed from Radiation Therapy Oncology Group (RTOG), MD Anderson Cancer Center (MDACC), and Yale University. METHODS: With C-statistics, the above-mentioned five staging algorithms were compared for overall and relapse-free survival endpoints in a multi-institutional cohort of OPSCC cases (n = 338) treated with primary surgery. RESULTS: Pathological UICC 8th ed yielded the highest C-indexes in the entire cohort and in the HPV- subset, whereas MDACC was superior for HPV+ OPSCC. RTOG was the simplest and holistic algorithm with a noninferior discriminatory power. CONCLUSION: UICC 8th ed, MDACC, and RTOG offer moderate and comparable efficacy for staging in this OPSCC patient cohort undergoing surgical treatment. Notable discrepancy between clinical and pathological UICC 8th ed algorithms poses potential concerns in diagnosis, treatment, research, and data management.

Effect of preoperative immunonutrition on postoperative short-term outcomes of patients with head and neck squamous cell carcinoma.

BACKGROUND: Patients with head and neck squamous cell carcinoma (HNSCC) often acquire an impaired nutritional status resulting in compromised outcomes. Perioperative immunonutrition may have a positive effect on outcomes after elective surgery. METHODS: Short-term outcomes before and after implementation of preoperative immunonutrition were retrospectively assessed. Regression models adjusted for outcome predictors were used to compare the length of stay (LOS) in the hospital, local infections, and general complications. RESULTS: Four hundred eleven patients were included (control group = 209 and the intervention group = 202). With immunonutrition, hospital LOS was significantly lower (median 6 vs 8 days; adjusted mean difference of -5.65 days; P < .001) and local infections were significantly reduced (7.4% vs 15.3%; adjusted odds ratio [OR] 0.30; P = .006). Subgroup analysis showed more pronounced effects in patients with previous radiotherapy and extensive surgery. CONCLUSION: Patients receiving preoperative immunonutrition had a shorter hospital LOS and a lower rate for wound infections and local complications. These effects remained robust after a multivariate adjustment.