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Purpose: Uncontrolled studies suggest that the addition of high-dose-rate intraluminal brachytherapy (HDRIB) to external beam radiation therapy (EBRT) may improve palliation for patients with advanced non-small cell lung cancer (NSCLC). The purpose of this study was to evaluate the potential clinical benefit of adding HDRIB to EBRT in a multicenter randomized trial., Methods and Materials: Patients with symptomatic stage III or IV NSCLC with endobronchial disease were randomized to EBRT (20 Gy in 5 daily fractions over 1 week or 30 Gy in 10 daily fractions over 2 weeks) or the same EBRT plus HDRIB (14 Gy in 2 fractions separated by 1 week). The primary outcome was the proportion of patients who achieved symptomatic improvement in patient-reported overall lung cancer symptoms on the Lung Cancer Symptom Scale (LCSS) at 6 weeks after randomization. Secondary outcomes included improvement in individual symptoms, symptom-progression-free survival, overall survival, and toxicity. The planned sample size was 250 patients based on detection of symptomatic improvement from 40% to 60% with a 2-sided α of .05 and 80% power., Results: A total of 134 patients were randomized over 4.5 years: 67 to each arm. The study closed early owing to slow accrual. The mean age was 69.8 years, and 67% of patients had metastatic disease. At 6 weeks, 19 patients (28.4%) in the EBRT arm and 20 patients (29.9%) in the EBRT plus HDRIB arm experienced an improvement in lung cancer symptoms (P = .84). When limited to patients who completed the LCSS, percentages were 40.4% versus 47.6%, respectively (P = .49). Between group differences in mean change scores (0.3-0.5 standard deviations) in favor of EBRT plus HDRIB were observed for overall symptoms, but only hemoptysis was significantly improved (P = .03). No significant differences were observed in progression-free or overall survival. Grade 3/4 toxicities were similar between groups., Conclusions: Small to moderate improvements were seen in symptom relief with the combined therapy, but they did not reach statistical significance. Further research is necessary before recommending HDRIB in addition to EBRT for palliation of lung cancer symptoms., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Obstructive symptoms that affect quality of life (QOL) are commonly caused by endobronchial disease in many patients with locally advanced, inoperable lung cancer. High-dose-rate endobronchial brachytherapy (HDREBBT) has been used to palliate these symptoms, yet its role is not well defined in the literature., Methods and Materials: Ninety-eight patients with locally advanced, inoperable lung cancer received HDREBBT. They were prospectively followed for survival, QOL, and toxicity endpoints. QOL measures were captured using the Quality of Life Questionnaire-Lung Cancer 30 and -Lung Cancer 13., Results: At 1-year follow-up, no significant toxicities were seen. Overall survival was 13.4% at 12 months (mean 192 days). Performance status, additional treatment after HDREBBT and treatment intent affected overall survival on univariate analysis (p < 0.05). Mean hemoptysis-free survival for all patients was 232.3 days, cough-free survival was 140.3 days, and dyspnea-free survival was 173.5 days. There was no impact of any treatment- or patient-related factors of these outcomes on multivariate analysis, including additional treatment modalities and HDREBBT dose., Conclusions: HDREBBT is a safe and effective way to palliate endobronchial symptoms. Additional external-beam radiation therapy, chemotherapy, or chemoradiation after HDREBBT improves survival, but does not affect QOL measures., (Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.)

Purpose: A 2D∕3D registration algorithm is proposed for registering orthogonal x-ray images with a diagnostic CT volume for high dose rate (HDR) lung brachytherapy., Methods: The algorithm utilizes a rigid registration model based on a pixel∕voxel intensity matching approach. To achieve accurate registration, a robust similarity measure combining normalized mutual information, image gradient, and intensity difference was developed. The algorithm was validated using a simple body and anthropomorphic phantoms. Transfer catheters were placed inside the phantoms to simulate the unique image features observed during treatment. The algorithm sensitivity to various degrees of initial misregistration and to the presence of foreign objects, such as ECG leads, was evaluated., Results: The mean registration error was 2.2 and 1.9 mm for the simple body and anthropomorphic phantoms, respectively. The error was comparable to the interoperator catheter digitization error of 1.6 mm. Preliminary analysis of data acquired from four patients indicated a mean registration error of 4.2 mm., Conclusions: Results obtained using the proposed algorithm are clinically acceptable especially considering the complications normally encountered when imaging during lung HDR brachytherapy.

It has been suggested that combination high dose rate (HDR) intraluminal brachytherapy and photodynamic therapy (PDT) in nonsmall cell lung cancer (NSCLC) may improve efficacy of treatment, reduce toxicity and enhance quality of life for patients. To provide a cellular basis for this we examined the in vitro sensitivity of MRC5 normal lung fibroblasts and four NSCLC cell lines following HDR radiation, PDT and combined HDR radiation and PDT. HDR radiation was cobalt-60 gamma rays (1.5-1.9 Gy min(-1)). For PDT treatment, cells were exposed to 2.5 microg mL(-1) Photofrin for 18-24 h followed by light exposure (20 mW cm(-2)). For combined treatment cells were exposed to Photofrin and then either exposed to light and 15-30 min later exposed to HDR radiation or exposed to HDR radiation and 15-30 min later exposed to light. D(37) values calculated from clonogenic survival curves indicated a six-fold difference in HDR radiation sensitivity and an eight-fold difference in PDT sensitivity. The effect of combined treatment was not significantly different from an additive effect of the individual treatment modalities for the NSCLC cells, but was significantly less than additive for the MRC5 cells. These results suggest an equivalent tumor cell kill may be possible at reduced systemic effects to patients.

Introduction: The epidermal growth factor receptor (EGFR) and its downstream effector kinases are thought to have important roles in lung cancer cell proliferation and response to treatment., Methods: In a prospective cohort of patients with locally advanced non-small cell lung cancer (NSCLC) undergoing high-dose radiotherapy with or without chemotherapy, we examined by immunohistochemistry (IHC) the tumor levels of EGFR and phosphorylated/ activated-EGFR (P-EGFR), P-Erk, P-Akt, P-Stat3, and the cell cycle marker Ki67. We examined the relationships among marker expression, at the plasma membrane (M), cytoplasm (C) and nucleus, as well as the radiologic tumor response, and overall survival (OS)., Results: Fifty patients were recruited in this study. Their median survival was 18.3 months. No correlation was detected between total EGFR and P-EGFR levels in any subcellular compartment. M P-EGFR correlated positively with C P-Akt (p = 0.01). C P-Erk correlated negatively with radiologic response (p = 0.022), and on univariate regression analysis, this approached significance (p = 0.059). M and C P-EGFR correlated negatively with OS (p = 0.020), and on univariate analysis higher M P-EGFR predicted for poor OS (p = 0.001). Patients with high M P-EGFR levels had median survival of 7.8 months versus 17.7 months for patients with low M P-EGFR., Conclusions: Our results support a role of activated M P-EGFR, (but not total EGFR), as a predictor of OS in locally advanced-NSCLC. It is suggested that detailed evaluation of the subcellular distribution and activation state of EGFR and its downstream effectors is required to unravel the predictive value of these markers in NSCLC.

The authors used data collected from 1995 to 1999, from an on-going cancer case-control study in greater Johannesburg, to estimate the importance of tobacco and alcohol consumption and other suspected risk factors with respect to cancer of the oesophagus (267 men and 138 women), lung (105 men and 41 women), oral cavity (87 men and 37 women), and larynx (51 men). Cancers not associated with tobacco or alcohol consumption were used as controls (804 men and 1370 women). Tobacco smoking was found to be the major risk factor for all of these cancers with odds ratios ranging from 2.6 (95% CI 1.5-4.5) for oesophageal cancer in female ex-smokers to 50.9 (95% CI 12.6-204.6) for lung cancer in women, and 23.9 (95% CI 9.5-60.3) for lung cancer and 23.6 (95% CI 4.6-121.2) for laryngeal cancer in men who smoked 15 or more grams of tobacco a day. This is the first time an association between smoking and oral and laryngeal cancers has been shown in sub-Saharan Africa. Long-term residence in the Transkei region in the southeast of the country continues to be a risk factor for oesophageal cancer, especially in women (odds ratio=14.7, 95% CI 4.7-46.0), possibly due to nutritional factors. There was a slight increase in lung cancer (odds ratio=2.9, 95% CI 1.1-7.5) in men working in 'potentially noxious' industries. 'Frequent' alcohol consumption, on its own, caused a marginally elevated risk for oesophageal cancer (odds ratio=1.7, 95% CI 1.0-2.9, for women and odds ratio=1.8, 95% CI 1.2-2.8, for men). The risks for oesophageal cancer in relation to alcohol consumption increased significantly in male and female smokers (odds ratio=4.7, 95% CI=2.8-7.9 in males and odds ratio=4.8, 95% CI 3.2-6.1 in females). The above results are broadly in line with international findings., (Copyright 2002 Cancer Research UK)