The impact of concurrent granulocyte macrophage-colony stimulating factor on radiation-induced mucositis in head and neck cancer patients: a double-blind placebo-controlled prospective phase III study by Radiation Therapy Oncology Group 9901.

PURPOSE: Based on early clinical evidence of potential mucosal protection by granulocyte-macrophage colony stimulating factor (GM-CSF), the Radiation Therapy Oncology Group conducted a double-blind, placebo-controlled, randomized study to test the efficacy and safety of GM-CSF in reducing the severity and duration of mucosal injury and pain (mucositis) associated with curative radiotherapy (RT) in head-and-neck cancer patients. METHODS AND MATERIALS: Eligible patients included those with head-and-neck cancer with radiation ports encompassing >50% of oral cavity and/or oropharynx. Standard RT ports were used to cover the primary tumor and regional lymphatics at risk in standard fractionation to 60-70 Gy. Concurrent cisplatin chemotherapy was allowed. Patients were randomized to receive subcutaneous injection of GM-CSF 250 microg/m2 or placebo 3 times a week. Mucosal reaction was assessed during the course of RT using the National Cancer Institute Common Toxicity Criteria and the protocol-specific scoring system. RESULTS: Between October 2000 and September 2002, 130 patients from 36 institutions were accrued. Nine patients (7%) were excluded from the analysis, 3 as a result of drug unavailability. More than 80% of the patients participated in the quality-of-life endpoint of this study. The GM-CSF did not cause any increase in toxicity compared with placebo. There was no statistically significant difference in the average mean mucositis score in the GM-CSF and placebo arms by a t test (p = 0.4006). CONCLUSION: This placebo-controlled, randomized study demonstrated no significant effect of GM-CSF given concurrently compared with placebo in reducing the severity or duration of RT-induced mucositis in patients undergoing definitive RT for head-and-neck cancer.

Microcystic adnexal carcinoma: report of four cases treated with Mohs' micrographic surgical technique.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a rare and aggressive malignant tumor of the sweat glands. Clinically, it often presents as a firm subcutaneous nodule on the head and neck regions. On histology, MAC exhibits both pilar and sweat duct differentiation with a stroma of dense collagen. It often extends beyond the clinical margins with local spreading in the dermal, subcutaneous, and perineural tissue planes. It has a high local recurrence rate after standard excision. Recent preliminary reports have indicated more favorable cure rates with Mohs' micrographic surgery (MMS). OBJECTIVE: To present our data on four cases of MAC treated by MMS. We also compared our findings with more recently reported series in the English language literature. METHODS: We reviewed the medical records of four patients (two males and two females) with MAC treated by MMS over the last 3 years. We also obtained follow-up data. RESULTS: In all four patients with MAC treated by MMS, there were no recurrences, with a mean follow-up of 1 year. CONCLUSION: We report an additional four MAC cases treated by MMS. The accumulated data continue to confirm that, if the diagnosis of MAC is made early, and if the anatomic location is accessible to excision by MMS, a favorable outcome can be expected.

Clinical investigation: Reliability and validity of the Japanese version of quality of life radiation therapy instrument (QOL-RTI) for Japanese patients with head and neck malignancies.

PURPOSE: To evaluate the reliability and validity of the Japanese translation of Quality of Life Radiation Therapy Instrument (QOL-RTI) and the head and neck module (H&N) for Japanese patients being treated with radiotherapy for head and neck malignancies. MATERIALS & METHODS: The QOL-RTI/H&N was translated into Japanese by a preliminary QOL research working group of JASTRO and was used in this clinical trial. From 1998 to 2001, 70 patients with head and neck malignancies for whom radical radiotherapy was planned were entered into this study. Patients were requested to answer the questions before radiotherapy at baseline, twice during week 4 of therapy (for test-retest reliability), at the end of treatment, and 3 months, 6 months, 1 year and 2 years from the beginning of radiotherapy. Internal consistency was assessed by Cronbach's alpha coefficient. Validity was assessed by comparing the results with EORTC-QLQ-C30 and with QOL questionnaire for cancer patients treated with anticancer drugs (QOL-ADC). Patient compliance and test sensitivity were also analyzed. RESULTS: Cronbach's alpha coefficient was 0.79 to 0.93 depending on the time point for the evaluation. Test-retest reliability was acceptable, with a Pearson coefficient of 0.83 for QOL-RTI and 0.92 for H&N module. Compliance with this scheme was 98.2%. The QOL-RTI was sensitive enough to detect significant changes in the QOL score during and after the course of radiotherapy. Agreement with the EORTC-C30 was good with a high Pearson correlation coefficient of 0.648 and that with QOL-ADC was also good with a coefficient of 0.566. The factors analyzed consisted of 11 functional/health-oriented questions, 5 emotional/ psychological, 5 socio-economic/ family and 2 general. CONCLUSION: The Japanese version of QOL-RTI with H&N module was found to be reliable and sensitive enough to evaluate variation of QOL in patients with head and neck malignancies during and after radiotherapy.

High-level expression of vascular endothelial growth factor and its receptors in an aphthous ulcer.

BACKGROUND: Aphthous ulcers are an extremely common disorder of unknown etiology. These ulcers cause significant morbidity through pain and interference with eating. Thalidomide, an angiogenesis inhibitor, is efficacious for the treatment of aphthous ulcers. METHODS: In situ hybridization was performed on an idiopathic aphthous ulcer using probes specific for the angiogenesis factor vascular endothelial growth factor, and its receptors, in order to determine whether these ulcers are highly angiogenic. CONCLUSIONS: Aphthous ulcers are highly angiogenic. Thalidomide may act to heal aphthous ulcers by inhibiting angiogenesis and promoting reepithelialization. Excess angiogenesis may inhibit reepithelialization in certain types of ulcers, and angiogenesis inhibitors may actually promote wound healing if ulcers are caused by excess angiogenesis.

Assessment of quality of life and oral function of patients participating in a phase II study of radioprotection of oral and pharyngeal mucosa by the prostaglandin E(1) analog misoprostol (RTOG 96-07).

PURPOSE: The oral complications associated with radiotherapy to the head and neck are a significant dose-limiting factor. The goals of this study were to determine whether oropharyngeal rinsing and ingestion of misoprostol protect mucous membranes from the acute effects of irradiation, and to evaluate the quality-of-life (QOL) outcomes of patients receiving misoprostol. We report the results of the QOL outcomes of patients in this study. METHODS AND MATERIALS: A total of 33 patients with resected or intact cancer of the oral cavity, oropharynx, supraglottic larynx, or hypopharynx were registered to receive postoperative radiotherapy plus misoprostol or primary radiotherapy plus misoprostol. All patients were scheduled to receive 60-70 Gy at 2 Gy/d within 6-7 weeks. QOL and function were evaluated. RESULTS: A decrease in the QOL and function occurred in all areas covered by the questionnaire at the 6-week interval. This decrease was significant for eating, saliva, taste, and mucous. Of these significant factors, taste, saliva, and mucous consistency had not resolved by 12 weeks. CONCLUSION: Increased understanding of the impact of treatment on QOL and symptoms will formulate the rational design of toxicity interventions and enhance the multidisciplinary care of head-and-neck patients.

Assessment of toxicity in cooperative oncology clinical trials: the long and short of it.

Cancer therapy is associated with inherent adverse effects and the need for complete, consistent and accurate reporting of toxicity is paramount in multicenter cooperative oncology clinical trials. Accurate toxicity information is essential to weigh the costs and benefits associated with new treatment regimens. A major issue faced by investigators and clinical trial coordinators today is the lack of clear directions regarding what method should be used in toxicity assessment in cooperative oncology clinical trials. Research personnel are faced with two options: (1) to be proactive and use a "directed" method of toxicity assessment or (2) to simply follow the data trail and report selected toxicity based only on routine documentation in the chart. The differences between these two approaches may be immense depending on one's perspective. The purpose of this article is to review how the current methods of toxicity assessment evolved and discuss issues and concerns in toxicity assessment in a challenging healthcare environment where clinical trials continue to increase in complexity and workload through the use of novel and multimodality therapies. The potential implications for toxicity data management practices, data quality, patient care management and resource utilization are discussed.

Measurement of quality of life in head and neck cancer patients utilizing the quality of life radiation therapy questionnaire.

BACKGROUND: Quality of life (QOL) measures give patients the possibility to express subjective changes in wellbeing. We aimed to translate the radiation specific quality of life questionnaire (QOL-RTI) and the companion head and neck module (H&N) questionnaire into German and to test its reliability, validity and sensitivity. PATIENTS AND METHODS: After translation and final revisions based on qualitative interviews with ten patients, 97 head and neck cancer patients were screened for eligibility. Patients answered the 38 items questionnaire at baseline and twice in week 4 of radiotherapy for test-retest reliability. Internal consistency was calculated using Chronbach's alpha. Patients also completed the functional assessment of cancer tool plus head and neck (FACT-G plus H&N) for concurrent validity. Item analyses were performed to test the sensitivity. RESULTS: Chronbach's alpha yielded alpha = 0.85 for the QOL-RTI and alpha = 0.80 for the H&N module, test-retest reliability scores were r = 0.87 and r = 0.83, respectively. The correlation of the QOL-RTI plus H&N and the FACT plus H&N was r = 0.79. Questionnaire sensitivity was supported by significant changes in the mean score of 45.8% of the QOL-RTI items and 78.6% of the H&N items between baseline and week 4 of radiotherapy. CONCLUSIONS: The German version of the QOL-RTI was shown to be a reliable, valid and sensitive tool to assess the quality of life of patients undergoing radiotherapy. The H&N module is useful for patients undergoing treatment for head and neck cancer.