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Objective An increased interval between symptomatic disease and treatment may negatively influence oncologic and/or functional outcomes in head and neck cancer (HNC). This systematic review aims to provide insight into the effects of time to treatment intervals on oncologic and functional outcomes in oral cavity, pharyngeal, and laryngeal cancer. Data Sources PubMed, EMBASE, and Cochrane library were searched. Review Methods All studies on delay or time to diagnosis or treatment in oral, pharyngeal, and laryngeal cancer were included. Quality assessment was performed with an adjusted version of the Newcastle-Ottawa scale. Outcomes of interest were tumor volume, stage, recurrence, survival, patient-reported outcome measures (PROMs), toxicity, and functionality after treatment. Results A total of 51 studies were included. Current literature on the influence of delay in HNC is inconsistent but indicates higher stage and worse survival with longer delay. The effects on PROMs, toxicity, and functional outcome after treatment have not been investigated. The inconsistencies in outcomes were most likely caused by factors such as heterogeneity in study design, differences in the definitions of delay, bias of results, and incomplete adjustment for confounding factors in the included studies. Conclusion Irrespective of the level of evidence, the unfavorable effects of delay on oncologic, functional, and psychosocial outcomes are undisputed. Timely treatment while maintaining high-quality diagnostic procedures and decision making reflects good clinical practice in our opinion. This review will pose practical and logistic challenges that will have to be overcome.

Repopulation of clonogenic tumor cells is inversely correlated with radiation treatment outcome in head and neck squamous cell carcinomas. A functional imaging tool to assess the proliferative activity of tumors could improve patient selection for treatment modifications and could be used for evaluation of early treatment response. The PET tracer 39-deoxy-39-18 F-fluorothymidine ( 18 F-FLT) can image tumor cell proliferation before and during radiotherapy, and it may provide biologic tumor information useful in radiotherapy planning. In the present study, the value of 18 F-FLT PET in determining the lymph node status in squamous cell carcinoma of the head and neck was assessed, with pathology as the gold standard. Methods: Ten patients with newly diagnosed stage II-IV squamous cell carcinoma of the head and neck underwent 18 F-FLT PET before surgical tumor resection with lymph node dissection. Emission 18 F-FLT PET and CT images of the head and neck were recorded and fused, and standardized uptake values (SUVs) were calculated. From all 18 18 F-FLT PET-positive lymph node levels and from 8 18 F-FLT PET-negative controls, paraffin-embedded lymph node sections were stained and analyzed for the endogenous proliferation marker Ki-67 and for the preoperatively administered proliferation marker iododeoxyuridine. The sensitivity, specificity, positive predictive value, and negative predictive value were calculated for 18 F-FLT PET. Results: Primary tumor sites were oral cavity (n 5 7), larynx (n 5 2), and maxillary sinus (n 5 1). Nine of the 10 patients examined had 18 F-FLT PET-positive lymph nodes (SUV mean : median, 1.2; range, 0.8-2.9), but only 3 of these patients had histologically proven metastases. All metastatic lymph nodes showed Ki-67 and iododeoxyuridine staining in tumor cells. In the remaining 7 patients, there was abundant Ki-67 and iododeoxyuridine staining of B-lymphocytes in germinal centers in PET-positive lymph nodes, explaining the high rate of false-positive findings. The sensitivity, specificity, positive predictive value, and negative predictive value of 18 F-FLT PET were 100%, 16.7%, 37.5%, and 100%, respectively. Conclusion: In head and neck cancer patients, 18 F-FLT PET showed uptake in metastatic as well as in nonmetastatic reactive lymph nodes, the latter due to reactive B-lymphocyte proliferation. Because of the low specificity, 18 F-FLT PET is not suitable for assessment of pretreatment lymph node status. This observation may also negatively influence the utility of 18 F-FLT PET for early treatment response evaluation of small metastatic nodes.

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Clinical research shows that nutritional intervention is necessary to prevent malnutrition in head and neck cancer patients undergoing radiotherapy. The objective of the present study was to assess the value of individually adjusted counselling by a dietitian compared to standard nutritional care (SC). A prospective study, conducted between 2005 and 2007, compared individual dietary counselling (IDC, optimal energy and protein requirement) to SC by an oncology nurse (standard nutritional counselling). Endpoints were weight loss, BMI and malnutrition (5 % weight loss/month) before, during and after the treatment. Thirty-eight patients were included evenly distributed over two groups. A significant decrease in weight loss was found 2 months after the treatment (P¼ 0·03) for IDC compared with SC. Malnutrition in patients with IDC decreased over time, while malnutrition increased in patients with SC (P¼ 0·02). Therefore, early and intensive individualised dietary counselling by a dietitian produces clinically relevant effects in terms of decreasing weight loss and malnutrition compared with SC in patients with head and neck cancer undergoing radiotherapy.