Mitchell Machtay

Bio: Mitchell Machtay is an academic researcher from University Hospitals of Cleveland. The author has contributed to research in topics: Radiation therapy & Head and neck cancer. The author has an hindex of 33, co-authored 180 publications receiving 5628 citations. Previous affiliations of Mitchell Machtay include Kettering Medical Center & Penn State Cancer Institute.

Factors Associated With Severe Late Toxicity After Concurrent Chemoradiation for Locally Advanced Head and Neck Cancer: An RTOG Analysis

Abstract: Purpose Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases both local tumor control and toxicity. This study evaluates clinical factors that are associated with and might predict severe late toxicity after CCRT. Methods Patients were analyzed from a subset of three previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis as chronic grade 3 to 4 pharyngeal/laryngeal toxicity (RTOG/European Organisation for the Research and Treatment of Cancer late toxicity scoring system) and/or requirement for a feeding tube ≥ 2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Case-control analysis was performed, with a multivariable logistic regression model that included pretreatment and treatment potential factors. Results A total of 230 patients were assessable for this analysis: 99 p...

Sequential vs Concurrent Chemoradiation for Stage III Non–Small Cell Lung Cancer: Randomized Phase III Trial RTOG 9410

Abstract: Background The combination of chemotherapy with thoracic radiotherapy (TRT) compared with TRT alone has been shown to confer a survival advantage for good performance status patients with stage III non–small cell lung cancer. However, it is not known whether sequential or concurrent delivery of these therapies is the optimal combination strategy.

Local recurrence in head and neck cancer: relationship to radiation resistance and signal transduction.

Abstract: Purpose: Locoregional recurrence is the dominant form of treatment failure in head and neck (H&N) cancer. The epidermal growth factor receptor (EGFR) is frequently amplified in this disease (≤80%) and can lead to activation of phosphatidylinositol-3-kinase (PI3K), both directly and indirectly through Ras. We have shown previously that radioresistance could be conferred via the Ras-PI3K pathway. Here we investigate the contribution of EGFR to this pathway and its impact on treatment outcome. Experimental Design: In a series of 38 H&N cancer patients, overexpression of EGFR by immunohistochemical staining was assessed. PI3K signaling was evaluated by staining for phosphorylated Akt (P-Akt), a downstream target of PI3K. Both EGFR and P-Akt were then related to outcome. Radiation survival was determined in the SQ20B cell line, a radioresistant squamous cell line derived from a recurrent laryngeal cancer, after pharmacological blockade of EGFR with Iressa, of Ras by the FTI L744,832, or of PI3K by LY294002. Results: A significant association was found between P-Akt staining and local control in the patient series. Two-year local control was 100% for patients staining 0–1+ for P-Akt as compared with 70.6% for patients staining 2–3+ ( P = 0.04). In our series of 38 H&N cancers, 30 (78.9%) of the specimens were strongly (3+) positive for EGFR, whereas 25 (65.8%) were moderately to strongly (2–3+) positive for P-Akt. Pharmacologically inhibiting EGFR, Ras, and PI3K led to radiosensitization of SQ20B cells. Conclusions: Evaluation of PI3K activation by Akt phosphorylation might be a prognostic marker for response to therapy, and PI3K could be a useful target for therapy. These results also suggest that signaling from EGFR to PI3K can lead to radioresistance.

Higher Biologically Effective Dose of Radiotherapy Is Associated With Improved Outcomes for Locally Advanced Non–Small Cell Lung Carcinoma Treated With Chemoradiation: An Analysis of the Radiation Therapy Oncology Group

Abstract: Purpose Patients treated with chemoradiotherapy for locally advanced non–small-cell lung carcinoma (LA-NSCLC) were analyzed for local-regional failure (LRF) and overall survival (OS) with respect to radiotherapy dose intensity. Methods and Materials This study combined data from seven Radiation Therapy Oncology Group (RTOG) trials in which chemoradiotherapy was used for LA-NSCLC: RTOG 88-08 (chemoradiation arm only), 90-15, 91-06, 92-04, 93-09 (nonoperative arm only), 94-10, and 98-01. The radiotherapeutic biologically effective dose (BED) received by each individual patient was calculated, as was the overall treatment time-adjusted BED (tBED) using standard formulae. Heterogeneity testing was done with chi-squared statistics, and weighted pooled hazard ratio estimates were used. Cox and Fine and Gray's proportional hazard models were used for OS and LRF, respectively, to test the associations between BED and tBED adjusted for other covariates. Results A total of 1,356 patients were analyzed for BED (1,348 for tBED). The 2-year and 5-year OS rates were 38% and 15%, respectively. The 2-year and 5-year LRF rates were 46% and 52%, respectively. The BED (and tBED) were highly significantly associated with both OS and LRF, with or without adjustment for other covariates on multivariate analysis ( p Conclusions Higher radiotherapy dose intensity is associated with improved local-regional control and survival in the setting of chemoradiotherapy.

Factors Associated with Severe Late Toxicity After Concurrent Chemoradiation for Locally Advanced Head and Neck Cancer: An RTOG Analysis

Abstract: Purpose Concurrent chemoradiotherapy (CCRT) for squamous cell carcinoma of the head and neck (SCCHN) increases both local tumor control and toxicity. This study evaluates clinical factors that are associated with and might predict severe late toxicity after CCRT. Methods Patients were analyzed from a subset of three previously reported Radiation Therapy Oncology Group (RTOG) trials of CCRT for locally advanced SCCHN (RTOG 91-11, 97-03, and 99-14). Severe late toxicity was defined in this secondary analysis as chronic grade 3 to 4 pharyngeal/laryngeal toxicity (RTOG/European Organisation for the Research and Treatment of Cancer late toxicity scoring system) and/or requirement for a feeding tube ≥ 2 years after registration and/or potential treatment-related death (eg, pneumonia) within 3 years. Case-control analysis was performed, with a multivariable logistic regression model that included pretreatment and treatment potential factors. Results A total of 230 patients were assessable for this analysis: 99 p...

Radiotherapy plus Cetuximab for Squamous-Cell Carcinoma of the Head and Neck

Abstract: BACKGROUND We conducted a multinational, randomized study to compare radiotherapy alone with radiotherapy plus cetuximab, a monoclonal antibody against the epidermal growth factor receptor, in the treatment of locoregionally advanced squamous-cell carcinoma of the head and neck. METHODS Patients with locoregionally advanced head and neck cancer were randomly assigned to treatment with high-dose radiotherapy alone (213 patients) or high-dose radiotherapy plus weekly cetuximab (211 patients) at an initial dose of 400 mg per square meter of body-surface area, followed by 250 mg per square meter weekly for the duration of radiotherapy. The primary end point was the duration of control of locoregional disease; secondary end points were overall survival, progression-free survival, the response rate, and safety. RESULTS The median duration of locoregional control was 24.4 months among patients treated with cetuximab plus radiotherapy and 14.9 months among those given radiotherapy alone (hazard ratio for locoregional progression or death, 0.68; P = 0.005). With a median follow-up of 54.0 months, the median duration of overall survival was 49.0 months among patients treated with combined therapy and 29.3 months among those treated with radiotherapy alone (hazard ratio for death, 0.74; P = 0.03). Radiotherapy plus cetuximab significantly prolonged progression-free survival (hazard ratio for disease progression or death, 0.70; P = 0.006). With the exception of acneiform rash and infusion reactions, the incidence of grade 3 or greater toxic effects, including mucositis, did not differ significantly between the two groups. CONCLUSIONS Treatment of locoregionally advanced head and neck cancer with concomitant highdose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck. (ClinicalTrials.gov number, NCT00004227.)

Multiple Imputation for Nonresponse in Surveys

Abstract: 25. Multiple Imputation for Nonresponse in Surveys. By D. B. Rubin. ISBN 0 471 08705 X. Wiley, Chichester, 1987. 258 pp. £30.25.

The biology and management of non-small cell lung cancer

Abstract: Important advancements in the treatment of non-small cell lung cancer (NSCLC) have been achieved over the past two decades, increasing our understanding of the disease biology and mechanisms of tumour progression, and advancing early detection and multimodal care. The use of small molecule tyrosine kinase inhibitors and immunotherapy has led to unprecedented survival benefits in selected patients. However, the overall cure and survival rates for NSCLC remain low, particularly in metastatic disease. Therefore, continued research into new drugs and combination therapies is required to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.