Jocelyn McLean

Randomized Controlled Trial of the Role of Positron Emission Tomography in the Management of Stage I and II Non-Small-Cell Lung Cancer

PURPOSE Positron emission tomography (PET) is a costly new technology with potential to improve preoperative evaluation for patients with non-small-cell lung cancer (NSCLC). There is increasing pressure for PET to be included in standard diagnostic work-up before decisions about surgical management of NSCLC. The resource implications of its widespread use in staging NSCLC are significant. METHODS A randomized controlled trial was conducted to investigate the impact of PET on clinical management and surgical outcomes for patients with stage I-II NSCLC. The primary hypothesis was that PET would reduce the proportion of patients with stage I-II NSCLC who underwent thoracotomy by at least 10% through identification of patients with inoperable disease. RESULTS One hundred eighty-four patients with stage I-II NSCLC were recruited and randomly assigned; 92% had stage I disease. Following exclusion of one ineligible patient, 92 patients were assigned to no PET and 91 to PET. Compared with conventional staging, PET upstaged 22 patients, confirmed staging in 61 and staged two patients as benign. Stage IV disease was rarely detected (two patients). PET led to further investigation or a change in clinical management in 13% of patients and provided information that could have affected management in a further 13% of patients. There was no significant difference between the trial arms in the number of thoracotomies avoided (P =.2). CONCLUSION For patients who are carefully and appropriately staged as having stage I-II disease, PET provides potential for more appropriate stage-specific therapy but may not lead to a significant reduction in the number of thoracotomies avoided.

Quality of Life and Survival in the 2 Years After Surgery for Non–Small-Cell Lung Cancer

PURPOSE Although surgery for early-stage non-small-cell lung cancer (NSCLC) is known to have a substantial impact on health-related quality of life (HRQOL), there are few published studies about HRQOL in the longer term. This article examines HRQOL and survival in the 2 years after surgery. PATIENTS AND METHODS Patients with clinical stage I or II NSCLC (n = 173) completed HRQOL questionnaires before surgery, at discharge, 1 month after surgery, and then every 4 months for 2 years. HRQOL was measured with a generic cancer questionnaire (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC-QLQ] C30) and a lung cancer-specific questionnaire (EORTC QLQ-LC13). Data were analyzed to examine the impact of surgery and any subsequent therapy, and to describe the trajectories of those who remained disease free at 2 years and those with recurrent cancer diagnosed during follow-up. RESULTS Disease recurred within 2 years for 36% of patients and 2-year survival was 65%. Surgery substantially reduced HRQOL across all dimensions except emotional functioning. HRQOL improved in the 2 years after surgery for patients without disease recurrence, although approximately half continued to experience symptoms and functional limitations. For those with recurrence within 2 years, there was some early postoperative recovery in HRQOL, with subsequent deterioration across most dimensions. CONCLUSION Surgery had a substantial impact on HRQOL, and although many disease-free survivors experienced recovery, some lived with long-term HRQOL impairment. HRQOL generally worsened with disease recurrence. The study results are important for informed decision making and ongoing supportive care for patients with operable NSCLC.

Guidelines for the diagnosis and treatment of malignant pleural mesothelioma

Malignant Pleural Mesothelioma (MPM), the asbestos-induced neoplasm originating in the mesothelial lining of the lung cavities represents significant diagnostic and therapeutic challenges for clinicians in Australia. Very seldom diagnosed prior to the advent of widespread asbestos mining in the early to midtwentieth century, it has sharply risen in incidence over the last five decades. According to the most recent Australian Institute of Health and Welfare data, there were 666 cases of malignant mesothelioma diagnosed in Australia in 2009 and around 90% of them originated in the pleura.

Extrapleural pneumonectomy for malignant pleural mesothelioma: outcomes of treatment and prognostic factors.

OBJECTIVE This study aimed to evaluate the perioperative and long-term outcomes associated with extrapleural pneumonectomy for patients with malignant pleural mesothelioma. METHODS From October 1994 to April 2008, 70 patients were selected for extrapleural pneumonectomy. Univariate analysis was performed using the Kaplan-Meier method and compared using the log-rank test. Multivariate analysis with entering and removing limits of P less than .10 and P greater than .05, respectively, was used. The prognostic factors included age, gender, side of disease, asbestos exposure, histology, positron emission tomography, date of surgery, neoadjuvant chemotherapy, completeness of cytoreduction, lymph node involvement, perioperative morbidity, adjuvant radiotherapy, and pemetrexed-based chemotherapy. RESULTS The mean age of patients was 55 years (standard deviation = 10). Fifty-eight patients had epithelial tumors. Six patients received neoadjuvant chemotherapy, 28 patients received adjuvant radiotherapy, and 16 patients received postoperative pemetrexed-based chemotherapy. Forty-four patients had no lymph node involvement. The perioperative morbidity and mortality were 37% and 5.7%, respectively. Complications included hemothorax (n = 7), atrial fibrillation (n = 6), empyema (n = 4), bronchopulmonary fistula (n = 3), right-sided heart failure (n = 2), pneumonia (n = 1), constrictive pericarditis (n = 1), acute pulmonary edema (n = 1), small bowel herniation (n = 1), and disseminated intravascular coagulopathy (n = 1). The median survival was 20 months, with a 3-year survival of 30%. Asbestos exposure, negative lymph node involvement, and receipt of adjuvant radiation or postoperative pemetrexed-based chemotherapy were associated with improved survival on both univariate and multivariate analyses. CONCLUSION The present study supports the use of extrapleural pneumonectomy-based multimodal therapy in carefully selected patients with malignant pleural mesothelioma.

Prognostic Features of Long-term Survivors After Surgical Management of Malignant Pleural Mesothelioma

BACKGROUND The primary aim of this study was to evaluate prognostic features of long-term survivors with pleural mesothelioma. METHODS Overall survival outcome was analyzed in 456 patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy (EPP), pleurectomy/decortications, or pleurodesis/biopsy with at least 18 months of follow-up. Prospectively collected clinicopathologic and treatment data were assessed for their correlations with actual 18-month survivors in both univariate and multivariate analyses. RESULTS The actual 18-month survival was 28%. Epithelial subtype was present in 185 patients (41%) and nonepithelial subtype in 183 (40%). Procedures were EPP in 59 patients (13%), pleurectomy/decortication in 250 (55%), and pleurodesis/biopsy in 147 (32%). Forty-two patients (9%) underwent positron emission tomography (PET) scanning. Forty patients (9%) received adjuvant radiotherapy and 45 (10%) received postoperative pemetrexed combination chemotherapy. In univariate analysis, age 65 years or younger (p < 0.001), malignant pleural effusion (p = 0.041), epithelial subtype (p < 0.001), EPP (p < 0.001), PET scan (p = 0.012), adjuvant radiotherapy (p = 0.042), and postoperative pemetrexed combination chemotherapy (p = 0.035) were strongly associated with 18-month survivors. In multivariate analysis, epithelial histopathologic subtype (p < 0.001) and EPP (p < 0.001) were independently associated with 18-month survivors. CONCLUSIONS The actual 18-month survival was 28% in 456 pleural mesothelioma patients who underwent operation. Epithelial histologic subtype and EPP were identified as independent predictors for 18-month survivors.

Node-Negative Non-small Cell Lung Cancer: Pathological Staging and Survival in 1765 Consecutive Cases

Introduction: This study aimed to evaluate prognostic factors in patients with node-negative non-small cell lung cancer and to assess revised International Association for the Study of Lung Cancer staging recommendations for this group. Methods: A retrospective analysis of 1765 consecutive pathologically node-negative patients treated by surgical resection between 1984 and 2007 was performed. Survival analysis was conducted using the Kaplan-Meier method. The independence of prognostic factors was analyzed using multivariate Cox proportional hazards modeling. Results: The median age of patients was 68 years, and the average length of follow-up was 6.3 years. Perioperative mortality was 1.7%. The median survival was 6.5 years, with a 56% of the cohort surviving 5 years. Factors associated with poorer prognosis were male gender (hazard ratio [HR]: 1.30, p = <0.001), age (HR: 1.04 per year of increase, p < 0.001), limited resection (HR: 1.30, p = 0.002) tumor size (HR: 1.10 per 10 mm increase, p < 0.001), large cell histopathological cell type (HR: 1.35, p < 0.001), and positive resection margins (HR: 1.58, p = 0.002). T stage was a superior predictor of survival than tumor size (p < 0.001). There was no difference in survival by T-stage descriptor within stage T2 or T3. Conclusions: In surgically treated, node-negative non-small cell lung cancer, revised International Association for the Study of Lung Cancer staging criteria stratify survival well. Age, gender, and extent of resection are also important predictors of survival. Current T-stage descriptor groupings are appropriate.

Hemithoracic radiation therapy after extrapleural pneumonectomy for malignant pleural mesothelioma: Toxicity and outcomes at an Australian institution.

We aim to report the outcome of patients with malignant pleural mesothelioma who underwent extrapleural pneumonectomy (EPP) and adjuvant hemithoracic radiotherapy with or without chemotherapy at a single Australian institution.

Pathological complete response in malignant pleural mesothelioma patients following induction chemotherapy: predictive factors and outcomes

A small proportion of patients with malignant pleural mesothelioma (MPM) achieve pathological complete response (CR) following treatment with current practice induction chemotherapy. Our analysis of 58 patients with MPM treated with platinum-based chemotherapy showed 4 patients (7%) attained pathological CR at subsequent extrapleural pneumonectomy (EPP). Patient and tumour factors such as age, gender, smoking habit, histological subtype, and clinical stage were not found to be associated with pathological CR. Patients with pathological CR had longer disease-free survival (29.2 vs. 13.8 months; p=0.08) and overall survival (76.4 vs. 23.4 months; p=0.06) but this did not reach statistical significance. Our study suggests that patients who achieve pathological CR after chemotherapy may have improved survival in MPM.