[Show abstract][Hide abstract] ABSTRACT: Malignant pleural mesothelioma (MPM) is a fatal malignancy associated with asbestos exposure. Although various therapies have been used in the past, including surgery, chemotherapy, radiotherapy, immunotherapy, and more recently targeted therapy, prognosis still remains poor. Radical
surgery including extrapleural pneumonectomy (EPP) or pleurectomy/decortication (P/D) is being offered to obtain maximal cytoreduction in the context of multimodality therapy in patients with MPM. Growing evidence suggests that EPP might be detrimental, while recent reports suggest that P/D
is better tolerated, producing low mortality and morbidity and allowing patients to receive adjuvant therapies in the form of either chemotherapy alone, or combined chemoradiotherapy. Many now believe that P/D should be the default procedure in multimodality regimens, although this remains
to be proven in a large randomized trial. Apart from its therapeutic role, surgery has also an important role to play in pleural mesothelioma in establishing or refining diagnosis and in controlling symptoms and improving quality of life in many patients whose life expectancy is limited. Recent
progress in molecular analyses and biomarkers should help with patient selection for surgery, immunotherapy and systemic therapies in the near future.
Journal of OncoPathology 02/2015; 3(1):41-53. DOI:10.13032/tjop.2052-5931.100120.
[Show abstract][Hide abstract] ABSTRACT: Objectives
to evaluate the long-term results of pleurectomy/decortication (P/D), hyperthermic pleural lavage with povidone-iodine, prophylactic chest wall radiotherapy (21 Gy) and systemic chemotherapy in patients with malignant pleural mesothelioma.
Retrospective cohort study of patients having surgery between January 2004 and December 2013. All patients received prophylactic radiotherapy postoperatively and all were supposed to receive systemic chemotherapy, either preoperatively or as adjuvant therapy. Patients were reviewed at 30 days, then followed up 6-monthly. 18-FDG-PET-CT was used routinely to diagnose disease recurrence. Second-line therapies were administered when appropriate. Survival and prognostic factors were analysed by the Kaplan-Meier method, log-rank test and Cox regression analysis.
One hundred and two patients had P/D followed by prophylactic radiotherapy and were referred for adjuvant chemotherapy. Median age at operation was 64 years. Eighty one patients (79.4%) were male. Fifty seven patients (55.9 %) had complete macroscopic resection. 30-day mortality was nil and 30 patients (29.4%) experienced postoperative complications. Seventy-three patients had epithelioid mesothelioma (71.5 %). Sixty eight patients (66.6%) had N0 disease. Ninety-six patients (94.1 %) received the planned 4-6 chemotherapy cycles. At last follow-up, 49 patients were alive. Univariate analysis showed no significant difference when sex, age > 70, nodal status, or prior chemotherapy were considered. The overall median survival was 32 months and 5-year survival was 23.1%. Median survival and 5-years survival rates were 35.0 months and 30.7% for epithelioid mesothelioma and 15. months and 7 % for non-epitheliod mesothelioma, respectively (p=0.0001). Median survival was 45.0 months for R0-R1 resection versus 17.4 months for R2 resection (p=0.0001).
Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine, prophylactic chest wall radiotherapy and systemic chemotherapy is a safe and well tolerated multi-modality therapy.
Journal of Thoracic and Cardiovascular Surgery 10/2014; 149(2). DOI:10.1016/j.jtcvs.2014.10.041 · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A universal and consistent stage classification system, which describes the anatomic extent of a cancer, provides a foundation for communication and collaboration. Thymic epithelial malignancies have seen little progress, in part because of the lack of an official system. The International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group assembled a large retrospective database, a multispecialty international committee and carried out extensive analysis to develop proposals for the 8th edition of the stage classification manuals. This tumor, node, metastasis (TNM)-based system is applicable to all types of thymic epithelial malignancies. This article summarizes the proposed definitions of the T, N, and M components and describes how these are combined into stage groups. This represents a major step forward for thymic malignancies.
Journal of Thoracic Oncology 09/2014; 9(9):S65-72. · 5.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite longstanding recognition of thymic epithelial neoplasms, there is no official American Joint Committee on Cancer/Union for International Cancer Control stage classification. This article summarizes proposals for classification of the T component of stage classification for use in the 8th edition of the tumor, node, metastasis classification for malignant tumors. This represents the output of the International Association for the Study of Lung Cancer and the International Thymic Malignancies Interest Group Staging and Prognostics Factor Committee, which assembled and analyzed a worldwide database of 10,808 patients with thymic malignancies from 105 sites. The committee proposes division of the T component into four categories, representing levels of invasion. T1 includes tumors localized to the thymus and anterior mediastinal fat, regardless of capsular invasion, up to and including infiltration through the mediastinal pleura. Invasion of the pericardium is designated as T2. T3 includes tumors with direct involvement of a group of mediastinal structures either singly or in combination: lung, brachiocephalic vein, superior vena cava, chest wall, and phrenic nerve. Invasion of more central structures constitutes T4: aorta and arch vessels, intrapericardial pulmonary artery, myocardium, trachea, and esophagus. Size did not emerge as a useful descriptor for stage classification. This classification of T categories, combined with a classification of N and M categories, provides a basis for a robust tumor, node, metastasis classification system for the 8th edition of American Joint Committee on Cancer/Union for International Cancer Control stage classification.
Journal of Thoracic Oncology 09/2014; 9(9):S73-80. · 5.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Stage classification is an important underpinning of management of patients with cancer, and rests on a combination of three components: T for tumor extent, N for nodal involvement, and M for more distant metastases. This article details an initiative to develop proposals for the first official stage classification system for thymic malignancies for the 8th edition of the stage classification manuals. Specifically, the results of analysis of a large database and the considerations leading to the proposed N and M components are described. Nodal involvement is divided into an anterior (N1) and a deep (N2) category. Metastases can involve pleural or pericardial nodules (M1a) or intraparenchymal pulmonary nodules or metastases to distant sites (M1b).
Journal of Thoracic Oncology 09/2014; 9(9):S81-7. · 5.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: This study aimed to assess the efficacy of thoracotomy and decortication (T/D) in achieving lung re-expansion in patients with Stage III empyema and assess the impact of culture-positive empyema on the outcome of decortication.
This is a retrospective observational study of consecutive patients treated with T/D over a 6-year period.
A total of 107 consecutive patients were identified. The median age was 55 (range 16-86) years; of which, 86% were male. The median length of hospital stay was 9 (range 2-45) days. Full lung re-expansion was achieved in 86% of cases. There were no postoperative deaths. Pleural cultures were positive in 56 (52%) cases. Patients with culture-positive empyema had a longer duration of pleural drainage (median of 11 days, range 3-112 versus median of 5 days, range 3-29 days for negative culture; P = 0.0004), longer length of hospital stay (median of 11 days, range 4-45 versus median of 7 days, range 2-34 days; P = 0.0002) and more complications (P = 0.0008), respectively. There was no statistically significant difference in the outcome of surgery, i.e. lung re-expansion versus trapped lung (P = 0.08) between the two groups.
T/D is safe and achieved lung re-expansion in the majority of patients. Culture-positive empyema was associated with worse outcomes.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 03/2014; 46(5). DOI:10.1093/ejcts/ezu104 · 3.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Malignant pleural mesothelioma is a fatal cancer developing in the pleural cavity, linked to asbestos exposure. Various therapies have been tried in the past 50 years including surgery, radiotherapy, chemotherapy, immunotherapy and more recently, targeted therapy. Radical surgery remains controversial in malignant pleural mesothelioma and two procedures have been offered in the past to obtain maximal cytoreduction: extrapleural pneumonectomy (EPP) and pleurectomy/decortication (P/D). Despite growing evidence that EPP might be detrimental, many believe that radical surgery should still be part of multimodality therapy in patients with malignant pleural mesothelioma. Recent evidence suggests that P/D is well tolerated and produces low mortality and morbidity. The role of adjuvant intrapleural therapies remains to be determined and evaluated in large prospective trials. Pleurectomy/decortication does not jeopardize the chance of having chemotherapy, or chemoradiotherapy either. Many now believe that it should be the default procedure in multimodality regimens. However, this remains to be proven in a large randomized trial. Palliative surgery still has an important role to play in mesothelioma, in establishing or refining diagnosis and in controlling symptoms and improving quality of life in many patients whose life expectancy is limited. Recent progress in molecular analyses and biomarkers should help with patient selection for surgery, immunotherapy and systemic therapies in the near future.
[Show abstract][Hide abstract] ABSTRACT: Chemotherapy or chemoradiotherapy is the recommended treatment for small cell lung cancer (SCLC), except in stage I disease where clinical guidelines state there may be a role for surgery based on favourable outcomes in case series. Evidence supporting adjuvant chemotherapy in resected SCLC is limited but this is widely offered.
Data on 359 873 patients who were diagnosed with a first primary lung cancer in England between 1998 and 2009 were grouped according to histology (SCLC or non-SCLC (NSCLC)) and whether they underwent a surgical resection. We explored their survival using Kaplan-Meier analysis and Cox regression, adjusting for age, sex, comorbidity and socioeconomic status.
The survival of 465 patients with resected SCLC was lower than patients with resected NSCLC (5-year survival 31% and 45%, respectively), but much higher than patients of either group who were not resected (3%). The difference between resected SCLC and NSCLC diminished with time after surgery. Survival was superior for the subgroup of 198 'elective' SCLC cases where the diagnosis was most likely known before resection than for the subgroup of 267 'incidental' cases where the SCLC diagnosis was likely to have been made after resection.
These data serve as a natural experiment testing the survival after surgical management of SCLC according to NSCLC principles. Patients with SCLC treated surgically for early stage disease may have survival outcomes that approach those of NSCLC, supporting the emerging clinical practice of offering surgical resection to selected patients with SCLC.
[Show abstract][Hide abstract] ABSTRACT: Malignant pleural mesothelioma (MPM) is a disease with poor prognosis despite multimodal therapy but there is variation in survival between patients. Prognostic information is therefore potentially valuable in managing patients, particularly in the context of clinical trials where patients could be stratified according to risk. Therefore we have evaluated the prognostic ability of parameters derived from baseline 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT).
In order to determine the relationships between metabolic activity and prognosis we reviewed all (18)F-FDG PET/CT scans used for pretreatment staging of MPM patients in our institution between January 2005 and December 2011 (n = 60) and measured standardised uptake values (SUV) including mean, maximum and peak values, metabolic tumour volume (MTV) and total lesion glycolysis (TLG). Overall survival (OS) or time to last censor was recorded, as well as histological subtypes.
Median follow-up was 12.7 months (1.9-60.9) and median OS was 14.1 months (1.9-54.9). By univariable analysis histological subtype (p = 0.013), TLG (p = 0.024) and MTV (p = 0.038) were significantly associated with OS and SUVmax was borderline (p = 0.051). On multivariable analysis histological subtype and TLG were associated with OS but at borderline statistical significance (p = 0.060 and 0.058, respectively). No statistically significant differences in any PET parameters were found between the epithelioid and non-epithelioid histological subtypes.
(18)F-FDG PET/CT parameters that take into account functional volume (MTV, TLG) show significant associations with survival in patients with MPM before adjusting for histological subtype and are worthy of further evaluation to determine their ability to stratify patients in clinical trials.
European Journal of Nuclear Medicine 09/2013; 41(2). DOI:10.1007/s00259-013-2561-1 · 5.38 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Surgery remains the best curative option in patients with early stage lung cancer (stage I and II). Developments in minimally invasive techniques now allow surgeons to perform lung resections on elderly patients, patients with poor pulmonary function or significant cardiopulmonary comorbidities. New techniques, such as stereotactic radiotherapy and ablative procedures, are being evaluated in early-stage lung cancer and may represent an alternative to surgery in patients unfit for lung resection. Perioperative mortality rates have dropped significantly at most institutions in the past two decades and complications are managed more efficiently. Progress in imaging and staging techniques have helped cut futile thoracotomy rates and offer patients the most adequate treatment options. Large randomised trials have helped clarify the role of neoadjuvant, induction and adjuvant chemotherapy, as well as radiotherapy. Surgery remains an essential step in the multimodality therapy of selected patients with advanced-stage lung cancer (stage III and IV). Interventional and endoscopic techniques have reduced the role of surgery in the diagnosis and staging of nonsmall cell lung cancer, but surgery remains an important tool in the palliation of advanced-stage lung cancer. Large national/international surgical databases have been developed and predictive risk-models for surgical mortality/morbidity published by learned surgical societies. Nonetheless, lung cancer overall survival rates remain deceptively low and it is hoped that early detection/screening, better understanding of tumour biology and development of biomarkers, and development of efficient targeted therapies will help improve the prognosis of lung cancer patients in the next decade.
European Respiratory Review 09/2013; 22(129):382-404. DOI:10.1183/09059180.00003913
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate the patterns of disease progression in patients treated with pleurectomy/decortication (P/D), hyperthermic pleural lavage with povidone-iodine, prophylactic radiotherapy and adjuvant chemotherapy, using F-fluorodeoxyglucose (F-FDG) PET/computed tomography (PET/CT).
This was a retrospective study of 65 patients treated with a multimodality therapy including P/D between October 2004 and March 2012. Thirty-two patients underwent F-FDG PET/CT within 6 weeks of completion of adjuvant chemotherapy and 6-monthly thereafter at our institution. The first site of relapse on F-FDG PET/CT was recorded, and all scans were reviewed by an independent observer.
Thirty-two patients (27 male, median age 61 years, range 45-73) underwent their F-FDG PET/CT scans at our institution. Eighteen of the 32 patients were alive at last follow-up (median follow-up 42 months, range 16-76). Nine patients were alive with disease recurrence. Fourteen patients died of disease progression (median survival 24.7 months, range 15-38). The median maximum standardized uptake value (SUVmax) in relapsing mesothelioma was 10.9 (range 4.9-27.3). There was a statistically significant correlation between the SUVmax and tumour lesion glycolysis of recurrent mesothelioma and overall survival (P=0.05). The site of disease recurrence was the pleura in the majority of the alive patients and was extrapleural in the dead patients. There was a statistically significant correlation between disease-free survival and complete macroscopic resection (P=0.02).
After P/D with hyperthermic pleural lavage with povidone-iodine, prophylactic radiotherapy and adjuvant chemotherapy, the most frequent site of recurrence is the pleural cavity. Peritoneal seeding is rare. The tumour SUVmax and tumour lesion glycolysis correlate significantly with overall survival.
Nuclear Medicine Communications 08/2013; 34(11). DOI:10.1097/MNM.0b013e3283653862 · 1.67 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction:
The incidence of mesothelioma is rising. First-line cisplatin and pemetrexed confers a survival benefit, with a median progression-free survival (PFS) of 5.7 months. Sorafenib inhibits tyrosine kinases, including receptors for vascular endothelial growth factor, which are implicated in mesothelioma pathogenesis by preclinical and clinical data.
Sorafenib, at 400 mg twice daily, was assessed in a single-arm multicenter phase 2 study, using Simon's two-stage design. Eligible patients had received platinum combination chemotherapy earlier. The primary endpoint was PFS at 6 months, with secondary endpoints, including response rate and metabolic response, assessed using fluorodeoxyglucose positron emission tomography. Published reference values for PFS in mesothelioma provide a benchmark for the null hypothesis of 28% progression-free at 6 months, and for moderate or significant clinical activity of 35% or 43% progression-free at 6 months, respectively.
Fifty-three patients (72%) were treated. Most had epithelioid histology. Ninety-three percent of patients had a performance status 0 or 1. Treatment was well tolerated with few grade 3 or 4 toxicities. Median PFS was 5.1 months, with 36% of patients being progression-free at 6 months. Nine percent of patients remained on study beyond 1 year. Changes in fluorodeoxyglucose positron emission tomography parameters did not predict clinical outcome.
Sorafenib is well tolerated in patients with mesothelioma after completion of platinum-containing chemotherapy. PFS of sorafenib compares favorably with that reported for other targeted agents, and suggests moderate activity in this disease.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 04/2013; 8(6). DOI:10.1097/JTO.0b013e31828c2b26 · 5.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Catamenial pneumothorax (CP) is a cause of recurrent pneumothorax in women of child-bearing age. Surgical treatment has been associated with high recurrence rates. We report our experience with a totally videothoracoscopic approach involving diaphragmatic repair, pleurectomy/abrasion, and hormonal treatment in patients with proven CP.
This was a retrospective study of all patients with proven CP operated on by a single surgeon using a videothoracoscopic approach, diaphragmatic repair, and pleurectomy/pleural abrasion. A polytetrafluoroethylene mesh was used to cover the diaphragm in patients with pores or fenestrations. All patients received hormone therapy for 6 to 12 months postoperatively and were followed up to assess complications and recurrence.
Twelve patients were identified as having CP. All patients except one had suffered right sided pneumothorax only. One patient also had a history of left-sided pneumothorax managed conservatively at another institution. All cases except one underwent a primary operation. One patient had previously had videothoracoscopic pleurodesis without diaphragm repair at another center. In all cases, findings typical of CP were identified within the pleural cavity, mainly on the diaphragm. In three patients, no diaphragmatic pores or fenestrations were noted. There were no postoperative complications and no mortality. Median follow-up was 45.8 28.6 months. One patient suffered a single episode of recurrence before starting hormonal therapy, treated conservatively.
A totally videothoracoscopic approach to CP including diaphragmatic cover with a mesh and pleurectomy/pleural abrasion is feasible, safe, and highly effective. Routine hormonal treatment (gonadotropin-releasing hormone analog) may also help reduce recurrences.
[Show abstract][Hide abstract] ABSTRACT: Tracheo-bronchial glomus tumours are rare, usually benign tumours of modified smooth muscle cells. They commonly present as non-specific respiratory symptoms of cough, dyspnoea or haemoptysis. Generally, glomus tumours are benign, but extension beyond the bronchial wall into surrounding soft tissues has been described. Surgical treatment remains the treatment of choice for tracheo-bronchial glomus tumours. Endobronchial therapy should be considered in patients unfit for surgical excision. We describe a patient with a glomus tumour of the left main bronchus, who presented with mediastinal shift and lung atelectasis, treated by left upper sleeve lobectomy. The resection was complete and the patient was discharged home after 8 days from surgery.
General Thoracic and Cardiovascular Surgery 05/2012; 60(11). DOI:10.1007/s11748-012-0078-3