On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapy.

BACKGROUND: Previous studies have suggested that inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and fibrinogen) are prognostic biomarkers in patients with a variety of solid cancers, including those treated with immune checkpoint inhibitors (ICIs). We aimed to develop a model that predicts response and survival in patients with relapsed and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy. METHODS: Analysis of 100 consecutive patients with unresectable R/M HNSCC who were treated with ICI. Baseline and on-treatment (day 28) NLR, fibrinogen and LDH were calculated and correlated with response, progression-free survival (PFS) and overall survival (OS) using univariate and multivariate analyses. The optimal cut-off values were derived using maximally selected log-rank statistics. RESULTS: Low baseline NLR and fibrinogen levels were associated with response. There was a statistically significant correlation between on-treatment NLR and fibrinogen and best overall response. On-treatment high NLR and raised fibrinogen were significantly associated with poorer outcome. In multivariate analysis, on-treatment NLR (≥4) and on-treatment fibrinogen (≥4 ng/mL) showed a significant negative correlation with OS and PFS. Using these cut-off points, we generated an on-treatment score for OS and PFS (0-2 points). The derived scoring system shows appropriate discrimination and suitability for OS (HR 2.4, 95% CI 1.7 to 3.4, p<0.0001, Harrell's C 0.67) and PFS (HR 1.8, 95% CI 1.4 to 2.3, p<0.0001, Harrell's C 0.68). In the absence of an external validation cohort, results of fivefold cross-validation of the score and evaluation of median OS and PFS on the Kaplan-Meier survival distribution between trained and test data exhibited appropriate accuracy and concordance of the model. CONCLUSIONS: NLR and fibrinogen levels are simple, inexpensive and readily available biomarkers that could be incorporated into an on-treatment scoring system and used to help predict survival and response to ICI in patients with R/M HNSCC.

A randomised controlled trial of Caphosol mouthwash in management of radiation-induced mucositis in head and neck cancer.

PURPOSE: This phase III, non-blinded, parallel-group, randomised controlled study evaluated the efficacy of Caphosol mouthwash in the management of radiation-induced oral mucositis (OM) in patients with head and neck cancer (HNC) undergoing radical (chemo)radiotherapy. PATIENTS AND METHODS: Eligible patients were randomised at 1:1 to Caphosol plus standard oral care (intervention) or standard oral care alone (control), stratified by radiotherapy technique and use of concomitant chemotherapy. Patients in the intervention arm used Caphosol for 7weeks: 6weeks during and 1-week post-radiotherapy. The primary endpoint was the incidence of severe OM (CTCAE ⩾grade 3) during and up to week 8 post-radiotherapy. Secondary endpoints include pharyngeal mucositis, dysphagia, pain and quality of life. RESULTS: The intervention (n=108) and control (n=107) arms were well balanced in terms of patient demographics and treatment characteristics. Following exclusion of patients with missing data, 210 patients were available for analysis. The incidence of severe OM did not differ between the intervention and control arms (64.1% versus 65.4%, p=0.839). Similarly, no significant benefit was observed for other secondary endpoints. Overall, compliance with the recommended frequency of Caphosol was low. CONCLUSION: Caphosol did not reduce the incidence or duration of severe OM during and after radiotherapy in HNC.

Fatigue during chemoradiotherapy for nasopharyngeal cancer and its relationship to radiation dose distribution in the brain.

BACKGROUND AND PURPOSE: Fatigue during head and neck radiotherapy may be related to radiation dose to the central nervous system (CNS). The impact of patient, tumour, and dosimetric variables on acute fatigue was assessed in nasopharyngeal cancer patients undergoing chemoradiotherapy. MATERIAL AND METHODS: Radiation dose to the following retrospectively-delineated CNS structures; brainstem, cerebellum, pituitary gland, pineal gland, hypothalamus, hippocampus and basal ganglia (BG) and clinical variables were related to incidence of ⩾ grade 2 fatigue in 40 patients. RESULTS: Sixty per cent of patients reported fatigue during and following radiotherapy. Dmean and D2 to the BG and Dmean to the pituitary gland were significantly associated with fatigue during radiation (P<0.01). Dmean to the cerebellum was associated with fatigue following radiotherapy and at any time (P < 0.01). After adjusting for clinical factors, an association remained between fatigue during radiotherapy and mean dose and D2 to the pituitary gland and BG (P = 0.012, 0.036, 0.009 and 0.018) and mean dose to the cerebellum following radiation and at any time (P = 0.042 and 0.029). CONCLUSION: Disruption of connections between BG, cerebellum, and higher cortical centres or disruption of pituitary-regulated hormonal balance may be implicated in the pathophysiology of radiation-related fatigue.

Tracheo-oesophageal party wall thickness in laryngectomised patients in India: implications for surgical voice restoration.

OBJECTIVE: To document accurately the tracheo-oesophageal party wall thickness (PWT) intra-operatively in patients undergoing total laryngectomy and to correlate it with constitutional parameters like height, weight, body mass index (BMI), age, and gender. Also, to correlate PWT with the length of tract (LOT), that is prosthesis size, as measured using the standard valve length measuring device provided by the manufacturers. METHODS: Twenty-eight patients of carcinoma larynx, following removal of the diseased larynx had their tracheo-oesophageal PWT measured using a special custom-designed and calibrated external (or outside) calliper and a primary trachea-oesophageal puncture (TOP) was made and inserted 10-14 days postoperative with an appropriately sized Blom-Singer(R) indwelling voice prosthesis. RESULTS: The mean PWT was 3.1 mm. PWT showed significant correlation with the weight of the patients (P = 0.006). There was no significant correlation between PWT and height, BMI, age or gender of the study group. The average LOT was found to be 4.8 mm (SD 1.5). There was a significant correlation (P = 0.009) between PWT and initial LOT, with the most commonly used prosthesis sizes being 4-6 mm. CONCLUSIONS: The study shows that Indian patients with a thin party wall require a smaller prosthesis size and it is advisable to measure the PWT intra-operatively. Tracheo-oesophageal PWT in laryngectomised patients in India: implications for surgical voice restoration.

Making sense of post-treatment surveillance in head and neck cancer: when and what of follow-up.

Follow-up in patients treated for head and neck cancer (HNC) is aimed at early detection of recurrence, metastases and second primary tumours. Various modalities for the routine follow-up of patients with HNC have been proposed and studied in the literature. Consequently, practising head and neck surgeons and oncologists all over the world use different guidelines and protocols to follow-up their patients. These guidelines involve follow-up intervals of varying intensity and schedule an assortment of investigations that may be neither logical nor practical. This follow-up process may be difficult to administrate, cause unnecessary discomfort and morbidity to the patient and can have serious cost-implications to the healthcare system. This review summarises strategies for follow-up, imaging modalities and key investigations in the literature published between 1980 and 2009. In this structured review, we have assessed studies in the literature that have addressed follow-up intervals, imaging tests, tumour markers, endoscopy and thyroid function tests as a part of the routine post-treatment surveillance in HNC patients. Studies analysing the cost benefit of such surveillance have also been addressed. Based on the evidence presented, we have compiled definitive recommendations for effective surveillance/post-treatment follow-up in patients with HNC.

Dysphagia in head and neck cancer.

Dysphagia is an important symptom of head and neck cancer (HNC), as well as representing a significant complication of its treatment. The treatment of HNC can result in neuromuscular and sensory damage affecting any stage of the swallow. The protective mechanisms during swallowing afforded by the structures in the pharynx are also affected in HNC. This article reviews the effect of the various treatment modalities in HNC on the swallowing mechanism. Various interventions which may play in role in relieving this dysphagia are also discussed. Due stress has been laid on the need for a multi-disciplinary approach for an optimal outcome in rehabilitating a patient's swallow after treatment for HNC.

Challenges for the future modifications of the TNM staging system for head and neck cancer: case for a new computational model?

The TNM system of staging cancers is a simple and effective method to map the extent of tumours. It had traditionally strived to maintain a balance between being simple and user-friendly on one hand and comprehensive on the other. A number of revisions have taken place over the years with the goal of improving utility. However, numerous controversies surround the TNM system. There is a school of thought that contends that patient co-morbidity and specific tumour-related factors should be incorporated to add further prognostic capabilities in the TNM system, but this raises concerns that such an approach may unnecessarily complicate the system. This review highlights some controversies that surround the TNM system and suggests prognostic indicators that may be added to make it more useful in guiding treatment decisions and predicting outcomes.

A short perspective on the surgical restoration of alaryngeal speech.

Despite advances in conservative laryngeal surgery and radiotherapy, total laryngectomy still remains the procedure of choice for advanced-stage laryngeal carcinoma around the world. The loss of natural voice is very often traumatic for the total laryngectomy patient, presenting lifelong challenges for communication in a world that relies heavily on verbal communication. Functional rehabilitation of these patients has long been one of the major challenges facing clinicians, but it is only in the last three decades that the emphasis on restoration of function and quality of life has become almost as important as cure and survival. Although voice restoration for alaryngeal speakers can be attained with any of 3 speech options - esophageal speech, electrolarynx and surgical voice restoration (SVR) using a valve the SVR technique has today become the preferred method and 'gold standard.' Successful tracheo-esophageal voice restoration in laryngectomy patients can be very rewarding, and patients are no longer condemned to silence while they await the results of their cancer treatments. They can face the challenges of life with the knowledge that a near-normal quality of life is very much possible.

Quality of life and outcomes research in head and neck cancer: a review of the state of the discipline and likely future directions.

Quality of life (QOL) is by definition a multi-dimensional global construct that has become an increasingly important outcome measure in cancer treatment. The impact of a head and neck cancer (HNC) diagnosis on the person and the consequences of its treatment cross multiple functional domains that have a clear and direct influence on one's post-treatment well-being and associated QOL. The evaluation of QOL and performance outcome in cancer is critical to optimal patient care, comprehensive evaluation of treatment alternatives, and the development of informed rehabilitation and patient education services. Despite the difficulties of going from concept to quantification of patient perceptions, the number of instruments available to measure QOL psychometrically has increased rapidly. Assessments can now be made in a variety of distinctive ways using both specific and generic measures. There is no gold-standard questionnaire and the choice is based on psychometric properties, research objectives and study design. QOL assessment has evolved over the years into an organised scientific discipline, such that useful insights can be obtained by a review of the current literature. However, more work needs to be done to improve the applicability and clinical utility of QOL assessment. Most importantly, QOL studies should be reported in such a way as to provide clinically meaningful data to physicians and surgeons, in order to link research to clinical practice. Further attention should be paid to the development of newer theoretical models, minimalist approaches, development of more sensitive and specific instruments and the effective use of modern technology to achieve this objective.