Nutritional support dependence after curative chemoradiotherapy in head and neck cancer: supplementary analysis of a phase II trial (JCOG0706S1).

OBJECTIVES: To explore the risk factors of laryngo-esophageal dysfunction-free survival and nutritional support dependence over 12 months in patients with unresectable locally advanced head and neck carcinomas who received chemoradiotherapy in a phase II trial of JCOG0706 (UMIN000001272). METHODS: Forty-five patients received radiation therapy for a total of 70 Gy/35fr concurrently with S-1 and cisplatin. Risk factors of laryngo-esophageal dysfunction-free survival and nutritional support dependence over 12 months were analyzed using Cox regression models and logistic regression models, respectively, with consideration to patient laboratory data just before chemoradiotherapy. Radiation fields were reviewed to analyze the relationship between the extent of the irradiated field and functional outcome. RESULTS: With a median follow-up period of 3.5 years, 3-year laryngo-esophageal dysfunction-free survival was 48.9%. For laryngo-esophageal dysfunction-free survival, hazards ratio of 2.35 in patients with nutritional support at registration (vs. without nutritional support; 95% confidence interval 0.96-5.76). For nutritional support dependence over 12 months, odds ratio was 6.77 in patients with hemoglobin less than the median of 13.4 g/dl (vs. higher than or equal to the median; 95% confidence interval 1.24-36.85) and was 6.00 in patients with albumin less than the median of 3.9 g/dl (vs. higher than or equal to the median; 95% confidence interval 1.11-32.54). Primary sites in disease-free patients with nutritional support dependence over 12 months were the oropharynx (N = 2) or hypopharynx (N = 1), and all pharyngeal constrictor muscles were included in irradiated fields with a curative dose. CONCLUSIONS: This supplementary analysis showed that pretreatment severe dysphagia requiring nutritional support, anemia and hypoalbuminemia might have a negative prognostic impact on long-term functional outcomes after curative chemoradiotherapy in head and neck cancer.

Renal protective effect of a hydration supplemented with magnesium in patients receiving cisplatin for head and neck cancer.

BACKGROUND: Our study analyzes the effect of magnesium supplementation on nephrotoxicity in patients receiving cisplatin for head and neck cancer. METHODS: We retrospectively reviewed the medical records of patients with head and neck cancer who received two doses of cisplatin (80 mg/m2) and 5-fluorouracil (800 mg/m2) 3 weeks apart from August 2008 to October 2012. The regimen prior to 2011 (crystalloid-only) involved the administration of 1000 mL of lactated Ringer's solution on the day prior to cisplatin infusion and 2000 mL of continuous infusion of saline on the day of cisplatin infusion. The regimen after 2011 (magnesium-supplemented) did not involve hydration on the day before cisplatin administration but used 1000 mL of 0.9% saline with magnesium sulfate (20 mEq) administered for 3 hours before cisplatin infusion. RESULTS: Sixty-five patients were treated with the crystalloid-only regimen and 56 patients with the magnesium-supplemented regimen. The mean creatinine clearance in the magnesium-supplemented group decreased by 4.9 mL/kg/min, whereas that in the crystalloid-only group decreased by 15.0 mL/kg/min after two courses. In multivariate analysis, only magnesium-supplemented hydration was an independent predictive factor for preventing cisplatin-induced nephrotoxicity (odds ratio = 0.157, 95% confidence interval 0.030-0.670, P = 0.0124). CONCLUSION: We demonstrated that an intravenous hydration regimen supplemented with magnesium prevented cisplatin-induced nephrotoxicity in patients with head and neck cancer.

Prospective randomized investigation implementing immunonutritional therapy using a nutritional supplement with a high blend ratio of ω-3 fatty acids during the perioperative period for head and neck carcinomas.

OBJECTIVES: The purpose of this study is to evaluate whether a nutritional supplement with a high blend ratio of ω-3 fatty acids can minimize weight loss and attenuate increases in inflammatory marker levels during the perioperative period in patients undergoing surgery for head and neck carcinoma. METHODS: Patients with ≥5% weight loss within 6 months were considered as targets for aggressive nutritional intervention. Among these patients, those with head and neck squamous cell carcinoma, who underwent major invasive surgery with free flap reconstruction were included in the present study. The patients were randomized into two groups: the 'nutritional supplementation group' and the 'non-intervention group'. The nutritional supplementation group received two packs of Prosure® (an eicosapentaenoic acid [EPA]-enriched oral nutritional supplement) per day for 28 days during the perioperative period. RESULTS: Compliance with the Prosure® dosage was very good at 6277/6720 ml (average) before surgery (93%) and 5229/6720 ml after surgery (78%), and a significant increase in EPA concentration was shown in the group that received Prosure® (P < 0.0001: Welch's t-test). However, 28 days of nutritional supplementation did not lead to further weight change or changes in the inflammatory marker levels of patients were already showing cachexia (based on weight loss). Interestingly, no further change in the mean weight was noted in these patients. The incidence of postoperative complications did not differ between the two groups. CONCLUSION: In this trial, immunonutritional therapy using a nutritional supplement with a high blend ratio of ω-3 fatty acids from 2 weeks before surgery until 2 weeks after surgery was not effective for maintaining the nutritional status of head and neck carcinoma patients.

The Impact of Skeletal Muscle Depletion on Head and Neck Squamous Cell Carcinoma.

BACKGROUND: Skeletal muscle depletion and sarcopenia have been reported as poor prognostic factors for several types of cancer. The aim of this study was to investigate the prognostic impact of skeletal muscle depletion and sarcopenia on the outcomes in head and neck cancer patients. METHODS: Patients with head and neck squamous cell carcinoma (HNSCC) treated from January 2013 to June 2014 were included in this study. The pretreatment cross-sectional area of skeletal muscle at the third lumbar vertebra (L3) was measured by computed tomography image analysis using the ImageJ software. L3 skeletal muscle index (SMI) and fat-free mass (FFM) were calculated. RESULTS: Eighty-five patients with HNSCC were included. The cut-off value of sarcopenia was set at SMI <46.7 cm2/m2 (males) and 30.3 cm2/m2 (females). The cut-off value of FFM was set at 42.3 kg (males) and 30.6 kg (females). Patients with a low SMI (sarcopenia) and low FFM had a significantly poorer prognosis than others, especially those who received definitive radiotherapy. Sarcopenia and low FFM are independent factors for poor prognosis in patients with HNSCC. CONCLUSION: The skeletal muscle area at L3 should be calculated when considering treatment options for head and neck cancer.

Clinical outcome and patterns of recurrence of head and neck squamous cell carcinoma with a limited field of postoperative radiotherapy.

BACKGROUND: Postoperative radiotherapy is the standard treatment for head and neck squamous cell carcinoma having high-risk features in surgical specimens. However, its severe toxicity can be a significant problem. This study was undertaken to evaluate the efficacy of our limited-field postoperative radiotherapy with the aim of reducing morbidity by minimizing the radiation field. METHODS: Between 2000 and 2009, 154 patients with head and neck squamous cell carcinoma received limited-field postoperative radiotherapy. The reason for postoperative radiotherapy was close/positive margins in 33 patients and extracapsular extension in 91. The median radiation dose was 50 Gy (30-66.4). The radiation field covered the tumor bed without lymph node regions for close/positive margins and only involved sites of the neck region were irradiated for multiple nodes or extracapsular extension. RESULTS: With a median follow-up of 43 months for surviving patients, the 3-year overall survival and progression-free survival rates were 53.7 and 42.1%, respectively. The 3-year rates of progression-free survival of the group having major risks (i.e. close/positive margins and/or extracapsular extension) and the group with other risks were 34.7 and 62.8%, respectively (P < 0.01). Thirty-one local recurrences (20%), of which 22 were located out-of-field, and 44 regional recurrences (29%), of which 16 were located out-of-field, developed. Late toxicity of grade 3 or greater developed in only six patients (3.8%). CONCLUSIONS: Although the toxicities associated with limited-field postoperative radiotherapy could be kept to lower levels, the locoregional control rate did not seem to be sufficient. We should arrange the radiation field depending on risk factors.