A double blind, randomised, placebo controlled, feasibility phase III clinical trial of peri-operative immune-enhancing enteral nutrition in patients undergoing surgery for advanced head and neck cancer

Purpose To report the impact of radiotherapy quality on outcome in a large international phase III trial evaluating radiotherapy with concurrent cisplatin plus tirapazamine for advanced head and neck cancer. Patients and Methods The protocol required interventional review of radiotherapy plans by the Quality Assurance Review Center (QARC). All plans and radiotherapy documentation underwent post-treatment review by the Trial Management Committee (TMC) for protocol compliance. Secondary review of noncompliant plans for predicted impact on tumor control was performed. Factors associated with poor protocol compliance were studied, and outcome data were analyzed in relation to protocol compliance and radiotherapy quality. Results At TMC review, 25.4% of the patients had noncompliant plans but none in which QARC-recommended changes had been made. At secondary review, 47% of noncompliant plans (12% overall) had deficiencies with a predicted major adverse impact on tumor control. Major deficiencies were unrelated to tumor subsite or to T or N stage (if N+), but were highly correlated with number of patients enrolled at the treatment center (< five patients, 29.8%; ≥ 20 patients, 5.4%; P < .001). In patients who received at least 60 Gy, those with major deficiencies in their treatment plans (n = 87) had a markedly inferior outcome compared with those whose treatment was initially protocol compliant (n = 502): −2 years overall survival, 50% v 70%; hazard ratio (HR), 1.99; P < .001; and 2 years freedom from locoregional failure, 54% v 78%; HR, 2.37; P < .001, respectively. Conclusion These results demonstrate the critical importance of radiotherapy quality on outcome of chemoradiotherapy in head and neck cancer. Centers treating only a few patients are the major source of quality problems.

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Randomized double-blind, placebo-controlled trial evaluating oral glutamine on radiation-induced oral mucositis and dermatitis in head and neck cancer patients

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy329 ◽

2019 ◽

Vol 109 (3) ◽

pp. 606-614 ◽

Cited By ~ 4

Author(s):

Chih-Jen Huang ◽

Ming-Yii Huang ◽

Pen-Tzu Fang ◽

Frank Chen ◽

Yu-Tsang Wang ◽

...

Keyword(s):

Head And Neck Cancer ◽

Head And Neck ◽

Cancer Patients ◽

Neck Cancer ◽

Oral Mucositis ◽

University Hospital ◽

Phase Iii ◽

Care Providers ◽

Double Blind ◽

Radiation Induced

ABSTRACT Background Glutamine is the primary fuel for the gastrointestinal epithelium and maintains the mucosal structure. Oncologists frequently encounter oral mucositis, which can cause unplanned breaks in radiotherapy (RT). Objectives The aim of this study was to explore the association between oral glutamine and acute toxicities in patients with head and neck cancer undergoing RT. Methods This was a parallel, double-blind, randomized, placebo-controlled Phase III trial conducted in a university hospital. A central randomization center used computer-generated tables to allocate interventions to 71 patients with stages I–IV head and neck cancers. The patients, care providers, and investigators were blinded to the group assignment. Eligible patients received either oral glutamine (5 g glutamine and 10 g maltodextrin) or placebo (15 g maltodextrin) 3 times daily from 7 d before RT to 14 d after RT. The primary and secondary endpoints were radiation-induced oral mucositis and neck dermatitis, respectively. These were documented in agreement with the National Cancer Institute Common Terminology Criteria for Adverse Events version 3. Results The study included 64 patients (placebo n = 33; glutamine n = 31) who completed RT for the completers’ analysis. Based on multivariate analysis, glutamine had no significant effect on the severity of oral mucositis (OR: 0.3; 95% CI: 0.05, 1.67; P = 0.169). Only the change in body mass index (BMI) was significant in both multivariate completers (OR: 0.41; 95% CI: 0.20, 0.84; P = 0.015) and per-protocol analysis (OR: 0.40; 95% CI: 0.20, 0.83; P = 0.014). No difference was found in the incidence and severity of neck dermatitis between the two arms. Conclusions The decrease in BMI was strongly related to the severity of oral mucositis in the head and neck cancer patients under RT, but not to the use of glutamine. This trial was registered at clinicaltrials.gov as NCT03015077.

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