Mark S. Chambers

The burdens of cancer therapy: Clinical and economic outcomes of chemotherapy-induced mucositis

Mucositis is a common but poorly studied problem among patients with solid tumors. The authors examined the clinical and economic outcomes of oral and gastrointestinal (GI) mucositis among patients receiving myelosuppressive chemotherapy.

Radiation-induced xerostomia in patients with head and neck cancer: Pathogenesis, impact on quality of life, and management

Xerostomia is a common, debilitating complication of radiation therapy (RT) for head and neck cancer. This article reviews the pathogenesis of radiation‐induced xerostomia, its impact on quality of life (QOL), and treatment options.

Adaptive Radiotherapy for Head-and-Neck Cancer: Initial Clinical Outcomes From a Prospective Trial

PURPOSE To present pilot toxicity and survival outcomes for a prospective trial investigating adaptive radiotherapy (ART) for oropharyngeal squamous cell carcinoma. METHODS AND MATERIALS A total of 24 patients were enrolled in an institutional review board-approved clinical trial; data for 22 of these patients were analyzed. Daily CT-guided setup and deformable image registration permitted serial mapping of clinical target volumes and avoidance structures for ART planning. Primary site was base of tongue in 15 patients, tonsil in 6 patient, and glossopharyngeal sulcus in 1 patient. Twenty patients (91%) had American Joint Committee on Cancer (AJCC) Stage IV disease. T stage distribution was 2 T1, 12 T2, 3 T3, 5 T4. N stage distribution was 1 N0, 2 N1, 5 N2a, 12 N2b, and 2 N2c. Of the patients, 21 (95%) received systemic therapy. RESULTS With a 31-month median follow-up (range, 13-45 months), there has been no primary site failure and 1 nodal relapse, yielding 100% local and 95% regional disease control at 2 years. Baseline tumor size correlated with absolute volumetric treatment response (p = 0.018). Parotid volumetric change correlated with duration of feeding tube placement (p = 0.025). Acute toxicity was comparable to that observed with conventional intensity-modulated radiotherapy (IMRT). Chronic toxicity and functional outcomes beyond 1 year were tabulated. CONCLUSION This is the first prospective evaluation of morbidity and survival outcomes in patients with locally advanced head-and-neck cancer treated with automated adaptive replanning. ART can provide dosimetric benefit with only one or two mid-treatment replanning events. Our preliminary clinical outcomes document functional recovery and preservation of disease control at 1-year follow-up and beyond.

A multinational, randomized phase iii trial of iseganan hcl oral solution for reducing the severity of oral mucositis in patients receiving radiotherapy for head-and-neck malignancy

PURPOSE Oral mucositis (OM) causes significant morbidity during the course of radiotherapy (RT) treatment of head-and-neck cancer. It is hypothesized that infection plays a role in the development of OM. We tested the efficacy of iseganan HCl (iseganan), a synthetic peptide with broad-spectrum antimicrobial activity, for preventing RT-associated OM. METHODS A multinational, randomized, double-blind, controlled trial was performed on patients receiving primary RT, primary chemoradiotherapy or postoperative RT. Patients were randomized to receive iseganan oral solution plus standard-of-care oral hygiene (SOC), placebo plus SOC, or SOC alone throughout the RT administration period. The severity of OM was assessed by NCI-CTC scoring and clinical symptoms by patient questionnaire. RESULTS A total of 545 patients were randomized to the study. Nine percent of the patients in both the iseganan and placebo groups did not develop ulcerative OM (Grades 2, 3, 4) (p = 0.998) whereas only 2% of the patients receiving SOC alone remained free of oral ulceration (p = 0.049). The maximum severity of mouth pain and difficulty swallowing did not differ in patients treated with iseganan or placebo. However, patients in both intervention groups reported less mouth pain and difficulty swallowing than did patients receiving SOC alone. Nausea was the only adverse event that occurred with >/=5% increased frequency in the iseganan group than in either the placebo or SOC groups (51% vs. 42% vs. 46%). Adverse events leading to study drug discontinuation and death did not differ significantly between groups. CONCLUSION Iseganan oral solution was safe but did not reduce the risk for developing ulcerative OM relative to placebo. Intensified oral hygiene or the administration of the vehicle used to deliver study drug in this trial appears to have reduced the risk and severity of OM. Our results suggest that antimicrobial intervention may not meaningfully affect the pathogenesis of radiation-induced OM.

Measuring head and neck cancer symptom burden: The development and validation of the M. D. Anderson symptom inventory, head and neck module

The aim of this study was to develop and validate a symptom inventory for patients with head and neck cancer and to assess the occurrence and severity of symptoms, the overall symptom burden, and the interference the symptoms cause in daily life.

Color stability of facial prostheses

The limited service of facial prostheses is the result of degradation of the elastomer and color instability. Deterioration may be caused by many factors, which include environmental exposure and changes in humidity. This investigation assessed the efficacy of an additive, intrinsic, broad-spectrum ultraviolet light absorber on the color stability of a pigmented facial elastomer. Samples were weathered artificially and outdoors at exposure levels of radiant energy of 150 to 450 kJ/m2. The samples changed color slightly but perceptibly. Artificial aging caused a greater change than outdoor aging. The ultraviolet light absorber UV-5411 did not protect the samples from color changes.

A Phase II Study of Gefitinib for Aggressive Cutaneous Squamous Cell Carcinoma of the Head and Neck

Purpose: To determine the disease control rate and toxicity of treating patients with aggressive cutaneous squamous cell carcinoma (CSCC) with neoadjuvant gefitinib. Experimental Design: A prospective phase II clinical trial evaluating neoadjuvant gefitinib given prior to standard treatment with surgery and/or radiotherapy. Patients with stable disease after one cycle received escalated doses. Patients who responded were given gefitinib during radiation therapy, as well as maintenance therapy after definitive treatment. We analyzed the correlation between epidermal growth factor receptor (EGFR) expression, mutation status, and gene copy number on available tissue samples and clinical response. Results: Twenty-three patients were accrued and 22 patients were evaluable for response prior to definitive local treatment; complete responses were attained by 18.2% of patients and partial responses by 27.3%. Grades 2 to 3 toxicities were observed in 59.1% of patients experiencing class-specific effects during induction therapy. After induction, 11.8% underwent surgery alone, 17.6% had definitive radiation, 11.8% were treated with radiation and concurrent gefitinib, and 47% had surgery with postoperative radiation and concurrent gefitinib. Median follow-up for the censored observations was 32 months. Two-year overall, disease-specific, and progression-free survival rates were 72.1%, 72.1%, and 63.6%, respectively. No EGFR-activating mutations were identified in tumor samples available from 10 patients. No associations between EGFR correlative studies and patient outcomes were identified. Conclusions: Gefitinib, in the neoadjuvant setting, was active and well tolerated in patients with aggressive CSCC and did not interfere with definitive treatment. In view of the 18% complete response rate we observed, EGFR tyrosine kinase inhibitors should be further explored in the treatment of aggressive CSCC. Clin Cancer Res; 18(5); 1435–46. ©2012 AACR.

Osteoradionecrosis of the Mandible: Treatment Outcomes and Factors Influencing the Progress of Osteoradionecrosis

PURPOSE The present study was undertaken to evaluate our recent experience with mandibular osteoradionecrosis (ORN) and to identify factors that contribute to its progress. PATIENTS AND METHODS The medical records of 114 patients who had been treated for ORN during a 16-year period (1989 to 2004) were reviewed. The patients were then divided into 2 groups according to their response to conservative treatment. Group 1 consisted of patients whose ORN resolved with conservative treatment (n = 47). Group 2 consisted of patients whose ORN was unresolved with conservative treatment or who had required radical resection of the involved tissue (n = 67). The information was obtained from the medical records of the patients and analyzed. RESULTS The patients whose ORN was associated with an early-stage tumor or preirradiation extraction had a favorable response to conservative treatment. However, those who had an advanced primary tumor, had continued smoking and drinking after radiotherapy, had received palliative radiotherapy or a radiation dose of more than 6,000 rads, and who had an orocutaneous fistula, a pathologic fracture, swelling, or trismus had a poor response to conservative treatment. In these latter cases, radical resection of the involved tissue proved useful. CONCLUSIONS The results of the present study have indicated that several factors (ie, the stage of the primary tumor, signs of ORN) can influence the progress of ORN. Our results suggest that radical resection is a useful method for treating mandibular ORN that does not respond to conservative treatment.

Randomized controlled trial of acupuncture for prevention of radiation‐induced xerostomia among patients with nasopharyngeal carcinoma

Xerostomia (dry mouth) after head/neck radiation is a common problem among cancer patients, and available treatments are of little benefit. The objective of this trial was to determine whether acupuncture can prevent xerostomia among head/neck patients undergoing radiotherapy.

Radiation-induced xerostomia

Radiation‐induced xerostomia is a frequent and usually permanent side effect of radiation therapy for head and neck cancer. We summarize recent developments in the prevention and treatment of radiation‐induced xerostomia.