Berghmans T.

Département des Soins Intensifs et Oncologie Thoracique, Institut Jules-Bordet (Centre des Tumeurs de l’Université Libre de Bruxelles), 1 Rue Héger-Bordet, Brussels, Belgium. thierry.berghmanns@bordet.be

Abstract

Malignant pleural mesothelioma is a rare tumour of poor prognosis. Available therapeutics have restricted efficacy. Pleuro-pneumonectomy is the only treatment with curative intent but it could be offered to a limited and well selected group of patients. The role of radiotherapy is palliative and its preventive role on malignant seeding after invasive procedures is controversial. There are few active cytotoxic drugs in this disease. Currently, based on two randomised trials, the most efficacious chemotherapy regimen consists in a combination of cisplatin and an antifolate agent, pemetrexed or raltitrexed.

Keywords: Mesothelioma, Surgery, Radiotherapy, Chemotherapy

Javedan K, Stevens CW, Forster K.

Radiation Oncology,1 H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, USA. khosrow.javedan@moffitt.org

Abstract

The present work investigated the potential of compensator-based intensity-modulated radiation therapy (CB-IMRT) as an alternative to multileaf collimator (MLC)-based intensity-modulated radiation therapy (IMRT) to treat malignant pleural mesothelioma (MPM) post extrapleural pneumonectomy. Treatment plans for 4 right-sided and 1 left-sided MPM post-surgery cases were generated using a commercial treatment planning system, XIO/CMS (Computerized Medical Systems, St. Louis, MO). We used a 7-gantry-angle arrangement with 6 MV beams to generate these plans. The maximum required field size was 30 x 40 cm. We evaluated IMRT plans with brass compensators (.Decimal, Sanford, FL) by examining isodose distributions, dose-volume histograms, metrics to quantify conformal plan quality, and homogeneity. Quality assurance was performed for one of the compensator plans. Conformal dose distributions were achieved with CB-IMRT for all 5 cases, the average planning target volume (PTV) coverage being 95.1% of the PTV volume receiving the full prescription dose. The average lung V20 (volume of lung receiving 20 Gy) was 1.8%, the mean lung dose was 6.7 Gy, and the average contralateral kidney V15 was 0.6%. The average liver dose V30 was 34.0% for the right-sided cases and 10% for the left-sided case. The average monitor units (MUs) per fraction were 980 MUs for the 45-Gy prescriptions (mean: 50 Gy) and 1083 MUs for the 50-Gy prescriptions (mean: 54 Gy). Post surgery, CB-IMRT for MPM is a feasible IMRT technique for treatment with a single isocenter. Compensator plans achieved dose objectives and were safely delivered on a Siemens Oncor machine (Siemens Medical Solutions, Malvern, PA). These plans showed acceptably conformal dose distributions as confirmed by multiple measurement techniques. Not all linear accelerators can deliver large-field MLC-based IMRT, but most can deliver a maximum conformal field of 40 x 40 cm. It is possible and reasonable to deliver IMRT with compensators for fields this size with most conventional linear accelerators.

Washino S, Terauchi F, Matsuzaki A, Kobayashi Y.

Department of Urology, Jichi Saitama Medical Center.

Abstract

We report here a case of malignant mesothelioma presenting as a perineal and intrascrotal mass. A 42-year-old Japanese male presented with an enlarging mass in the perineum and intrascrotum. Although the initial clinical diagnosis was perineal abscess, angiography revealed a tumor in the perineum and intrascrotum. The tumor was resected, and the pathological examination revealed malignant mesothelioma. Two months after the operation, a hard irregular mass with severe hemorrhage was noticed in the perineum, and was resected. A few weeks after the second operation local recurrence and, inguinal and intrapelvic retroperitoneal lymphadenopathy were found. Radiotherapy to recurrent sites was not effective. The patient died six months after the initiation of therapy. To our knowledge, 24 cases of malignant mesothelioma in the perineum or intrascrotum were reported in Japan and this case was thought to be the 25th case in Japan.

Gaspar LE, Ding M.

University of Colorado Denver, Department of Radiation Oncology, Campus Mail Stop F-706, 1665 North Ursula Street, Suite 1032, P.O. Box 6510, Aurora, CO 80045, USA. Laurie.Gaspar@uchsc.edu

Abstract

Intensity-modulated radiation therapy (IMRT) is a sophisticated form of three-dimensional treatment planning and delivery. In some situations, IMRT allows more conformal radiation therapy to complex targets within the lung. As problems related to organ motion are increasingly addressed, the use of IMRT in the treatment of lung cancer, particularly in non-small cell lung cancer and mesothelioma, continues to rise.

Di Salvo M, Gambaro G, Pagella S, Manfredda I, Casadio C, Krengli M.

Radiotherapy, University of Piemonte Orientale-Hospital Maggiore della Carità, Novara, Italy.

Abstract

Introduction: Literature data show that mesothelioma cells can implant along the surgical pathway of invasive procedures such as thoracotomy and thoracoscopy. We investigated the use of hypofractionated radiotherapy for preventing such malignant seeding.

Material and methods: Thirty-two consecutive patients diagnosed with pleural mesothelioma were included in the present retrospective study. All patients underwent surgery and/or thoracoscopy for diagnosis, staging or talc pleurodesis. They were treated with electron external beam radiation therapy (21 Gy in 3 fractions over 1 week), directed to the surgical pathway after the invasive procedure. After completion of radiation treatment, 20 of 32 patients (63%) underwent chemotherapy.

Results: After a mean follow-up of 13.6 months (range 3-41) from the end of radiation therapy, no patient had tumour progression in the treated area. The treatment was well tolerated, as only erythema grade I (Radiation Therapy
Oncology Group, RTOG, scale) was noted in 11 patients. Seventeen patients died of disease with local progression after a mean survival time of 12.6 months (range 3-27); thirteen patients are alive with disease after a mean follow-up of 13.9 months (range 4-41); two patients are alive without evidence of disease after a mean follow-up of 16.50 months (range 6-27).

Discussion: The present study shows the efficacy and safety of local radiotherapy in preventing malignant seeding after thoracoscopy in patients with pleural mesothelioma although larger prospective trials are probably still needed to validate this treatment approach.

Ramalingam SS, Belani CP.

Emory University School of Medicine, Winship Cancer Institute, Atlanta, Georgia, USA.

Abstract

Malignant pleural mesothelioma clinically manifests after decades of initial exposure to etiologic agents, such as asbestos, and presents with nonspecific symptoms such as dyspnea, pain, or weight loss. In patients with limited, resectable disease, surgical therapy with extrapleural pneumonectomy or pleurectomy is recommended, although, it is unclear which approach is superior. Radiation has a limited role and is used primarily for palliation. The palliative efficacy of traditional chemotherapeutic agents and combination regimens is modest at best. The combination of cisplatin and pemetrexed, a novel multitargeted antifolate agent, is the approved "standard of care" for patients with unresectable malignant pleural mesothelioma. A number of molecularly targeted agents are currently under evaluation for mesothelioma such as the Histone deacetylase (HDAC) inhibitors that have demonstrated promising anticancer activity. Vorinostat, a small molecule inhibitor of HDAC, which targets select members of class I and II HDACs, has shown early evidence of activity and is currently being evaluated in a randomized study for patients who progress with standard therapy for advanced mesothelioma. It is hoped that the HDAC inhibitors and other novel targeted agents will pave the way for improved outcomes for patients with this disease.

Nakas A, Trousse DS, Martin-Ucar AE, Waller DA.

Department of Thoracic Surgery, Glenfield Hospital, Groby Road, Leicester LE3 9QA, United Kingdom.

Abstract

Objective: To identify the optimal debulking procedure in patients with malignant pleural mesothelioma who are not suitable for extrapleural pneumonectomy (EPP).

Methods: We reviewed 102 consecutive patients (93 male; 9 female, mean age 63 years) who were not suitable for EPP because of either advanced tumour stage or suboptimal fitness. Patients underwent either a non-radical tumour decortication to obtain lung expansion (group NR) or latterly a radical pleurectomy/decortication to obtain macroscopic tumour clearance (group R). We analysed the comparative perioperative courses and long-term survival.

Results: The two groups were similar for age and gender distribution but epithelioid type was more predominant in group R: 78% compared to 55% epithelioid in group NR. Thirty-day mortality was similar (5.9% in group R and 9.8% in the group NR, p = 0.36) but 90-day mortality was significantly higher in the group NR (29.4% vs 9.8% in group R, p = 0.012). More patients in group R received adjuvant chemotherapy (65% vs 28%, p = 0.000) and radiotherapy (65% vs 26%, p = 0.000). Median survival for all cell types was significantly higher in group R (15.3 months vs 7.1 months, p < 0.000). Group R survival rates at 1, 2, 3 and 4 years were 53, 41, 25 and 13%, respectively while for group NR they were 32, 9.6, 2 and 0%, respectively. For epithelioid cell type there was still a significant median survival advantage in group R (25.4 months vs 10.2 months, p < 0.000), but there was no difference for sarcomatoid (9.3 months vs 3.2 months, p = 0.16) or biphasic cell types (9.4 months vs 7 months, p = 0.38).

Conclusion: If a patient with epithelioid MPM is fit enough to tolerate a thoracotomy then macroscopic clearance of the tumour is the preferred option as part of a multimodality regime including chemotherapy.

Keywords: Malignant pleural mesothelioma; Radical surgery; Pleurectomy/decortication

Hasegawa S, Tanaka F.

Department of Thoracic Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, 663-8501, Japan, hasegawa@hyo-med.ac.jp.

Abstract

Malignant pleural mesothelioma (MPM) is associated with a poor prognosis; and to make things worse, its incidence is increasing throughout the world. Surgical management of MPM is comprised of two aspects: diagnosis and resection. Surgical biopsy with thoracoscopy provides a higher yield but a higher rate of tumor cell seeding than blind biopsy. In some surgical cases, extended surgical staging with mediastinoscopy, laparoscopy, and contralateral thoracoscopy is required for the preoperative evaluation for resectablity. There are two types of surgical resection for MPM. Pleurectomy/decortication (P/D) involves removal of as much of the visceral, parietal, and pericardial pleura and the tumor as possible without removing the underlying lung. Because P/D is less radical but less invasive compared to extrapleural pneumonectomy (EPP), it can be tolerated by poor-risk patients. EPP comprises en bloc resection of visceral, parietal, and pericardial pleura and adjacent components such as ipsilateral lung, pericardium, and diaphragm, without opening the pleural cavity. EPP was considred a highly dangerous procedure with a surgical mortality of more than 30% decades ago, but its current operative mortality/morbidity rates are 4%-9% and 60%, respectively. As macroscopic complete resection is the primary goal of surgery for MPM because of its diffuse intrapleural growth, surgical resection alone is associated with poor survival. In this context, combination therapy with surgery plus chemotherapy and/or radiotherapy is currently considered the standard treatment for patients with respectable MPM. A national survey of EPP was conducted recently in Japan, and a few multicenter clinical trials will start soon

Keywords: Malignant pleural mesothelioma – Pleurectomy – Extrapleural pneumonectomy – Chemotherapy – Multimodality treatment

Sienel W, Kirschbaum A, Passlick B.

Abteilung Thoraxchirurgie, Chirurgische Universitätsklinik, Universitätsklinikum Freiburg.

Abstract

Multimodal therapy including neoadjuvant chemotherapy with subsequent extrapleural pneumonectomy and postoperative radiotherapy has been shown to improve the survival of patients with malignant pleural mesothelioma (MPM) if they are selected carefully. Careful patient selection is required in order to administer aggressive multimodal therapy only to patients who will benefit from such a treatment. To achieve an accurate staging (≤ cT3, < pN2, cM0), mediastinoscopy is recommended in addition to computed tomography of the chest and upper abdomen. Currently, neoadjuvant chemotherapy with pemetrexed and cisplatin followed by extrapleural pneumonectomy and postoperative radiotherapy is claimed to afford the best treatment results. We have treated 17 patients with such a regimen and achieved a 3-year survival rate of 76 % so far. During the follow-up duration of 23 months, 3 patients (18 %) developed distant metastasis and one (6 %) a mediastinal local recurrence. Multimodal therapy of malignant pleural mesothelioma including extrapleural pneumonectomy should only be performed in specialised centres for thoracic surgery where uncomplicated interdisciplinary communication is the rule and which provide the required expertise in patient selection, operative technique and postoperative care.

Keywords: malignant pleural mesothelioma – multimodal therapy – trimodal therapy – interdisciplinary cooperation – extrapleural pneumonectomy – pemetrexed

Barone-Adesi F, Ferrante D, Bertolotti M, Todesco A, Mirabelli D, Terracini B, Magnani C.

Unit of Cancer Epidemiology, CeRMS and Center for Oncologic Prevention Piemonte, University of Turin, Turin, Italy.

Abstract

Models based on the multistage theory of carcinogenesis predict that the rate of mesothelioma increases monotonically as a function of time since first exposure (TSFE) to asbestos. Predictions of long-term mortality (TSFE >/= 40 years) are, however, still untested, because of the limited follow-up of most epidemiological studies. Some authors have suggested that the increase in mesothelioma rate with TSFE might be attenuated by clearance of asbestos from the lungs. We estimated mortality time trends from pleural and peritoneal cancer in a cohort of 3,443 asbestos-cement workers, followed for more than 50 years. The functional relation between mesothelioma rate and TSFE was evaluated with various regression models. The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalized to include a term representing elimination over time. We observed 139 deaths from pleural and 56 from peritoneal cancer during the period 1950-2003. The rate of pleural cancer increased during the first 40 years of TSFE and reached a plateau thereafter. In contrast, the rate of peritoneal cancer increased monotonically with TSFE. The model allowing for asbestos elimination fitted the data better than the traditional model for pleural (p = 0.02) but not for peritoneal cancer (p = 0.22). The risk for pleural cancer, rather than showing an indefinite increase, might reach a plateau when a sufficiently long time has elapsed since exposure. The different trends for pleural and peritoneal cancer might be related to clearance of the asbestos from the workers’ lungs.

Keywords: asbestos, mesothelioma, multi-stage model, latency, clearance