Outcomes toolbox for head and neck cancer research.

BACKGROUND: Clinical research in head and neck cancer traditionally focused on tumor control. As survival improves, it is increasingly recognized that the side-effects of multimodality treatment can be profound and enduring. Thus, clinical trials require patient-reported and functional outcomes. METHODS: A subcommittee of the Previously Untreated, Locally Advanced (PULA) Task Force of the Head and Neck Steering Committee of the Coordinating Centre for Clinical Trials at the National Cancer Institute (NCI) was convened to identify a set of instruments suitable for widespread application in the conduct of clinical trials for head and neck cancer. RESULTS: Based on existing literature and expert opinion, 18 main areas of concern were identified. For each, measures suitable for use in multicenter clinical trials were recommended on the basis of validity, feasibility, and clinical acceptance. CONCLUSION: Suitable instruments exist for most head and neck cancer concerns, but gaps require further development. Future efforts should be made to harmonize measurement across trials.

The role of radiation therapy in the management of cutaneous melanoma.

Radiation therapy plays an integral role in the management of melanoma. Radiation therapy is infrequently needed for the treatment of the primary site, but there are occasions when it is appropriate. The role of adjuvant radiation therapy to resected nodal basins is becoming clearer from recent randomized data for patients at high risk. The role of radiotherapy combined with radiosensitizers, biologic or with hyperthermia, continues to evolve. Radiation therapy plays a vital role in the treatment of brain metastases and is useful for other systemic metastases. Emerging technology such as stereotactic radiation therapy may be useful in achieving durable palliation for selected patients.

Prognostic factors for survival after salvage reirradiation of head and neck cancer.

PURPOSE: Patients who develop recurrent or new primary head and neck cancer in a previously irradiated site have poor prognosis. Reirradiation is a treatment option, although it is associated with substantial toxicities. We investigated potential prognostic factors, including comorbidity and pre-existing organ dysfunction, for survival after reirradiation. METHODS: Institutional electronic records of patients treated with reirradiation between January 1998 and 2008 were reviewed. Comorbidity was assessed by Charlson index and Adult Comorbidity Evaluation-27 (ACE-27) grading. Organ dysfunction was defined as feeding tube dependency, functioning tracheostomy, or soft tissue defect. RESULTS: There were 103 patients, including 46 patients who underwent salvage surgery before reirradiation. Median progression-free and overall survivals were 12.1 months (95% CI, 9.7 to 16.6) and 19.3 months (95% CI, 13.9 to 29.9), respectively. Significant comorbidity was present in 36% of patients by Charlson index and 24% by ACE-27. Baseline organ dysfunction was present in 37% of patients. Median overall survivals were 5.5 months among those with both organ dysfunction and comorbidity per Charlson index, and 4.9 months per ACE-27, compared with 59.6 and 44.2 months, respectively, among the patients with neither organ dysfunction nor comorbidity (P < .001 and < .001). Other independent prognostic factors were interval from previous radiation, recurrent tumor stage, tumor bulk at reirradiation, and reirradiation dose. A nomogram to predict the probability of death within 24 months after reirradiation was developed (concordance index = 0.75). CONCLUSION: Comorbidity and pre-existing organ dysfunction are among several important prognostic factors for patients undergoing reirradiation. For those with both comorbidity and organ dysfunction, reirradiation largely serves as a palliative therapy.

Strategies for managing radiation-induced mucositis in head and neck cancer.

Radiation-induced mucositis (RIM) is a common toxicity for head and neck cancer (HNC) patients. The frequency has increased because of the use of more intensive altered radiation fractionation and concurrent chemotherapy regimens. The extent of the injury is directly related to the mucosal volume irradiated, anatomic subsite exposed, treatment intensity, and individual patient predisposition. The consequences of mucositis include pain, dysphagia including feeding tube dependency, dehydration, micronutrient deficiencies, weight loss, and potentially life-threatening aspiration. Currently, there is no Food and Drug Administration-approved cytoprotective agent that reliably prevents RIM for HNC, but several are under investigation. Strategies to limit the extent of mucositis and to manage its symptoms include basic oral care and supportive medications. Limiting the use of aggressive treatments to truly high-risk cancers and special attention to radiation therapy planning techniques can also help restrict the scope of the problem. This review focuses on mucositis recognition, patient treatment selection, and RIM symptom-management strategies.

Evaluation of early and late toxicities in chemoradiation trials.

Combined chemoradiotherapy is increasingly becoming a standard of care for the nonoperative management of a variety of solid malignancies. A string of randomized controlled phase III trials have shown statistically significant and clinically relevant improvements in outcome, ostensibly without any apparent increase in late toxicity. However, the reliability and the sensitivity of toxicity reporting in most trials are questionable. Audits and phase IV studies suggest that the chemoradiotherapy success comes at a price in terms of late toxicity. This review presents some of the challenges in recording, analyzing, and reporting toxicity data. METHODS for summarizing toxicity are reviewed, and a new investigational metric, the TAME reporting system, is discussed. The need for special vigilance in the era of molecular-targeted agents is emphasized because of the possibility that unexpected serious adverse events with a low incidence may occur. Finally, we discuss how progress in molecular pathology and radiation biology may provide novel opportunities for stratifying patients according to risk of adverse effects, interventional targets for reducing or treating adverse effects, and surrogate markers of normal-tissue injury.