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Mosleh B, Schwarz S, Cho A, Sinn K, Steindl A, Zöchbauer‐Müller S, Köstler WJ, Dieckmann K, Heilmann M, Widder J, Gompelmann D, Aigner C, Klikovits T, Hoda MA. Impact of Neoadjuvant and Adjuvant Pleural Intensity-Modulated Radiotherapy in Multimodality Treatment for Malignant Pleural Mesothelioma. Thorac Cancer 2025; 16:e70024. [PMID: 40066644 PMCID: PMC11894436 DOI: 10.1111/1759-7714.70024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Revised: 02/07/2025] [Accepted: 02/11/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND Few malignancies provoke as many controversies about treatment as pleural mesothelioma. There is limited experience with novel radiotherapy techniques worldwide in adjuvant and particularly in neoadjuvant settings within multimodality treatment. The objective of the current study was to investigate the long-term outcome of neoadjuvant and adjuvant pleural intensity-modulated radiotherapy (IMRT) combined with macroscopic complete resection with or without chemotherapy. METHODS We retrospectively analyzed a consecutive cohort of 59 patients who were diagnosed with pleural mesothelioma and underwent multimodality treatment including macroscopic complete resection and neoadjuvant or adjuvant IMRT between 2005 and 2019 at the Department of Thoracic Surgery, Medical University of Vienna, Austria. RESULTS In total, 59 patients (median age 59 years; IQR 54-66, male, n = 48; 81%) were included. Forty-seven patients underwent trimodality treatment consisting of induction chemotherapy, extrapleural pneumonectomy, and adjuvant IMRT. Novel neoadjuvant IMRT with (n = 9) or without (n = 3) chemotherapy followed by extrapleural pneumonectomy was performed in 12 patients. Median overall survival (OS) of all patients was 23.2 months (95% CI; 18.1-28.2) and 3- and 5-year survival rates were 33% and 28%, respectively. Survival was comparable between therapies including neoadjuvant versus adjuvant IMRT (median OS 17.5 vs. 24.0 months, p = 0.39). CONCLUSIONS Neoadjuvant pleural IMRT has been investigated as a novel treatment option for highly selected cases in pleural mesothelioma. Neoadjuvant IMRT was effective and safe in patients treated in a high-volume institution but showed no relevant survival benefit compared to adjuvant IMRT within multimodality treatment.
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Affiliation(s)
- Berta Mosleh
- Department of Thoracic Surgery, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
| | - Stefan Schwarz
- Department of Thoracic Surgery, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
| | - Anna Cho
- Department of NeurosurgeryMedical University of ViennaViennaAustria
| | - Katharina Sinn
- Department of Thoracic Surgery, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
| | - Ariane Steindl
- Division of Oncology, Department of Internal Medicine I, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
| | - Sabine Zöchbauer‐Müller
- Division of Oncology, Department of Internal Medicine I, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
| | - Wolfgang J. Köstler
- Division of Oncology, Department of Internal Medicine I, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
| | - Karin Dieckmann
- Department of Radiation Oncology, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
| | - Martin Heilmann
- Department of Radiation Oncology, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
| | - Joachim Widder
- Department of Radiation Oncology, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
| | - Daniela Gompelmann
- Division of Pulmonology, Department of Internal Medicine II, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
| | - Clemens Aigner
- Department of Thoracic Surgery, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
| | - Thomas Klikovits
- Department of Thoracic Surgery, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
| | - Mir Alireza Hoda
- Department of Thoracic Surgery, Comprehensive Cancer CenterMedical University of ViennaViennaAustria
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Kaplan MA, Şendur MAN, Cangır AK, Fırat P, Göker E, Kılıçkap S, Oyan B, Büge Öz A, Özdemir F, Özyiğit G. Established and new treatment roadmaps for pleural mesothelioma: opinions of the Turkish Collaborative Group. Curr Probl Cancer 2023; 47:101017. [PMID: 37845104 DOI: 10.1016/j.currproblcancer.2023.101017] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Revised: 08/16/2023] [Accepted: 09/05/2023] [Indexed: 10/18/2023]
Abstract
Pleural mesothelioma (PM) is a cancer of the pleural surface, which is aggressive and may be rapidly fatal. PM is a rare cancer worldwide, but is a relatively common disease in Turkey. Asbestos exposure is the main risk factor and the most common underlying cause of the disease. There have been significant improvements in diagnoses and treatments of many malignancies; however, there are still therapeutic challenges in PM. In this review, we aimed to increase the awareness of health care professionals, oncologists, and pulmonologists by underlining the unmet needs of patients with PM and by emphasizing the need for a multidisciplinary treatment and management of PM. After reviewing the general information about PM, we further discuss the treatment options for patients with PM using immunotherapy and offer evidence for improvements in the clinical outcomes of these patients because of these newer treatment modalities.
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Affiliation(s)
- Muhammet Ali Kaplan
- Department of Medical Oncology, Dicle University Hospitals Faculty of Medicine, Diyarbakır, Turkey.
| | - Mehmet Ali Nahit Şendur
- Department of Medical Oncology, Ankara Yıldırım Beyazıt University Faculty of Medicine, Ankara, Turkey
| | - Ayten Kayı Cangır
- Department of Thoracic Surgery, Ankara University Faculty of Medicine, Ibni Sina Hospital, Ankara, Turkey
| | - Pınar Fırat
- Department of Pathology, Koc University School of Medicine, Istanbul, Turkey
| | - Erdem Göker
- Department of Medical Oncology, Ege University Faculty of Medicine, Izmir, Turkey
| | - Saadettin Kılıçkap
- Department of Medical Oncology, Liv Hospital Ankara, Ankara, Turkey; Department of Medical Oncology, Istinye University Faculty of Medicine, Istanbul, Turkey
| | - Başak Oyan
- Department of Medical Oncology, Acıbadem University Faculty of Medicine, Istanbul, Turkey
| | - Ayşim Büge Öz
- Department of Medical Pathology, Istanbul University Cerrahpaşa Faculty of Medicine, Istanbul, Turkey
| | - Feyyaz Özdemir
- Department of Medical Oncology, Karadeniz Technical University, Trabzon, Turkey
| | - Gökhan Özyiğit
- Department of Radiation Oncology, Hacettepe University Faculty of Medicine, Ankara, Turkey
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Parekh AD, Indelicato DJ, Hoppe BS, Vega RBM, Rotondo RL, Bradley JA. Pulmonary dose tolerance in hemithorax radiotherapy for Ewing sarcoma of the chest wall: Are we overestimating the risk of radiation pneumonitis? Pediatr Blood Cancer 2021; 68:e29287. [PMID: 34398486 DOI: 10.1002/pbc.29287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 07/28/2021] [Accepted: 08/02/2021] [Indexed: 11/06/2022]
Abstract
BACKGROUND Children with chest wall Ewing sarcoma with malignant pulmonary effusion or pleural stranding require hemithorax radiation, often with plans that exceed lung constraints. We investigated disease control and pneumonitis in children requiring hemithorax radiation. PROCEDURE Eleven children (median age 13 years) received hemithorax radiotherapy. Symptomatic radiation pneumonitis was considered National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) grade 1+ with respiratory symptoms. Mean lung dose (MLD), volume of lung exposed to a dose ≥5 Gy (V5), ≥20 Gy (V20), and ≥35 Gy (V35) were recorded. Adult and pediatric lung constraints were obtained from Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines and Children's Oncology Group (COG) protocols, respectively. RESULTS Median hemithorax dose was 15 Gy (1.5 Gy/fraction). Median total dose was 51 Gy (1.8 Gy/fraction). Most plans delivered both protons and photons. The ipsilateral MLD, V5, and V20 were 27.2 Gy, 100%, and 48.3%; the bilateral MLD, V20, and V35 were 14.1 Gy, 22.8%, and 14.3%, respectively. One hundred percent, 36%, and 91% of treatments exceeded recommended adult ipsilateral lung constraints of V5 <65%, V20 <52%, and MLD of 22 Gy; 64%, 45%, and 82% exceeded COG bilateral lung constraints of V20 <20%, MLD <15 Gy, and MLD <12 Gy, respectively; 82% of treatments exceeded the COG ipsilateral lung constraint of V20 <30%. At a median 36 months (range 12-129), the symptomatic radiation pneumonitis incidence was 0%. Two patients progressed with nonpulmonary metastatic disease and died at a median 12 months following radiotherapy. CONCLUSIONS Existing guidelines may overestimate pneumonitis risk, even among young children receiving multiagent chemotherapy. For children with chest wall Ewing sarcoma and other thoracic malignancies, more data are needed to refine pediatric dose-effect models for pulmonary toxicity.
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Affiliation(s)
- Akash D Parekh
- Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida, USA
| | - Daniel J Indelicato
- Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida, USA
| | - Bradford S Hoppe
- Department of Radiation Oncology, Mayo Clinic, Jacksonville, Florida, USA
| | - Raymond B Mailhot Vega
- Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida, USA
| | - Ronny L Rotondo
- Department of Radiation Oncology, University of Kansas School of Medicine, Kansas City, Kansas, USA
| | - Julie A Bradley
- Department of Radiation Oncology, University of Florida College of Medicine, Jacksonville, Florida, USA
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Luna J, Bobo A, Cabrera-Rodriguez JJ, Pagola M, Martín-Martín M, Ruiz MÁG, Montijano M, Rodríguez A, Pelari-Mici L, Corbacho A, Moreno M, Couñago F. GOECP/SEOR clinical guidelines on radiotherapy for malignant pleural mesothelioma. World J Clin Oncol 2021; 12:581-608. [PMID: 34513595 PMCID: PMC8394157 DOI: 10.5306/wjco.v12.i8.581] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2020] [Revised: 05/12/2021] [Accepted: 07/06/2021] [Indexed: 02/06/2023] Open
Abstract
Malignant pleural mesothelioma (MPM) is a rare tumor with poor prognosis and rising incidence. Palliative care is common in MPM as radical treatment with curative intent is often not possible due to metastasis or extensive locoregional involvement. Numerous therapeutic advances have been made in recent years, including the use of less aggressive surgical techniques associated with lower morbidity and mortality (e.g., pleurectomy/decortication), technological advancements in the field of radiotherapy (intensity-modulated radiotherapy, image-guided radiotherapy, stereotactic body radiotherapy, proton therapy), and developments in systemic therapies (chemotherapy and immunotherapy). These improvements have had as yet only a modest effect on local control and survival. Advances in the management of MPM and standardization of care are hampered by the evidence to date, limited by high heterogeneity among studies and small sample sizes. In this clinical guideline prepared by the oncological group for the study of lung cancer of the Spanish Society of Radiation Oncology, we review clinical, histologic, and therapeutic aspects of MPM, with a particular focus on all aspects relating to radiotherapy, including the current evidence base, associations with chemotherapy and surgery, treatment volumes and planning, technological advances, and reradiation.
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Affiliation(s)
- Javier Luna
- Department of Radiation Oncology, Institute of Oncohealth, Fundación Jiménez Díaz, Madrid 28040, Spain
| | - Andrea Bobo
- Department of Radiation Oncology, Institution of Ruber Internacional Hospital, Madrid 28034, Spain
| | | | - María Pagola
- Department of Radiation Oncology, Institution of Onkologikoa/Hospital Universitario Donostia, San Sebastián 20014, Spain
| | - Margarita Martín-Martín
- Department of Radiation Oncology, Institution of Hospital Universitario Ramón y Cajal, Madrid 28034, Spain
| | - María Ángeles González Ruiz
- Department of Radiation Oncology, Institution of Hospital Universitario Virgen de la Macarena, Sevilla 41009, Spain
| | - Miguel Montijano
- Department of Radiation Oncology, Institution of Genesis care Spain, Madrid 28005, Spain
| | - Aurora Rodríguez
- Department of Radiation Oncology, Institution of Ruber Internacional Hospital, Madrid 28034, Spain
| | - Lira Pelari-Mici
- Department of Radiation Oncology, Institution of Hospital Universitario Ramón y Cajal, Madrid 28034, Spain
| | - Almudena Corbacho
- Department of Radiation Oncology, Institution of Hospital de Mérida, Mérida 06800, Spain
| | - Marta Moreno
- Department of Oncology, Institution of University Navarra, Clinical University, Pamplona 31008, Spain
| | - Felipe Couñago
- Department of Radiation Oncology, Institution of Hospital Universitario Quirónsalud and Hospital LaLuz, European University of Madrid, Madrid 28028, Spain
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Schumann SO, Kocher G, Minervini F. Epidemiology, diagnosis and treatment of the malignant pleural mesothelioma, a narrative review of literature. J Thorac Dis 2021; 13:2510-2523. [PMID: 34012597 PMCID: PMC8107529 DOI: 10.21037/jtd-20-2761] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The malignant pleural mesothelioma is a very aggressive tumor which is arising from mesothelial cells and is associated with asbestos exposure. It is a heterogeneous cancer that shows a complex pattern of molecular changes, including genetic, chromosomic, and epigenetic abnormalities. The malignant pleural mesothelioma is characterized by a silent and slow clinical progression with an average period of 20–40 years from the asbestos exposure phase to the start of the symptoms. Unfortunately, to date, the therapeutic options are very limited, especially if the tumor is detected late. This narrative review provides an extended overview of the present evidence in the literature regarding the epidemiology, diagnostic pathways and treatment approaches of the malignant pleural mesothelioma. The treatment of mesothelioma has evolved slowly over the last 20 years not only from a surgical point of view but also radiotherapy, chemotherapy and immunotherapy play nowadays a key role. Several surgical strategies are available ranging from extrapleural pneumonectomy to cytoreductive surgery but a multidisciplinary approach seems to be mandatory because a single approach has not proved to date to be resolutive. New non-surgical treatment options appear to be promising but the results have to be taken in account with caution because clear evidence with high-quality studies is still lacking
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Affiliation(s)
| | - Gregor Kocher
- Division of General Thoracic Surgery, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Fabrizio Minervini
- Department of Thoracic Surgery, Lucerne Cantonal Hospital, Lucerne, Switzerland
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Patel NV, Yu NY, Koroulakis A, Diwanji T, Sawant A, Sio TT, Mohindra P. Proton therapy for thoracic malignancies: a review of oncologic outcomes. Expert Rev Anticancer Ther 2021; 21:177-191. [PMID: 33118427 DOI: 10.1080/14737140.2021.1844567] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Introduction: Radiotherapy is an integral component in the treatment of the majority of thoracic malignancies. By taking advantage of the steep dose fall-off characteristic of protons combined with modern optimization and delivery techniques, proton beam therapy (PBT) has emerged as a potential tool to improve oncologic outcomes while reducing toxicities from treatment.Areas covered: We review the physical properties and treatment techniques that form the basis of PBT as applicable for thoracic malignancies, including a brief discussion on the recent advances that show promise to enhance treatment planning and delivery. The dosimetric advantages and clinical outcomes of PBT are critically reviewed for each of the major thoracic malignancies, including lung cancer, esophageal cancer, mesothelioma, thymic cancer, and primary mediastinal lymphoma.Expert opinion: Despite clear dosimetric benefits with PBT in thoracic radiotherapy, the improvement in clinical outcomes remains to be seen. Nevertheless, with the incorporation of newer techniques, PBT remains a promising modality and ongoing randomized studies will clarify its role to determine which patients with thoracic malignancies receive the most benefit. Re-irradiation, advanced disease requiring high cardio-pulmonary irradiation volume and younger patients will likely derive maximum benefit with modern PBT.
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Affiliation(s)
- Nirav V Patel
- Department of Radiation Oncology, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Nathan Y Yu
- Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, AZ, USA
| | - Antony Koroulakis
- Department of Radiation Oncology, University of Maryland School of Medicine and Maryland Proton Treatment Center, Baltimore, MD, USA
| | - Tejan Diwanji
- Department of Radiation Oncology, University of Miami Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Amit Sawant
- Department of Radiation Oncology, University of Maryland School of Medicine and Maryland Proton Treatment Center, Baltimore, MD, USA
| | - Terence T Sio
- Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, AZ, USA
| | - Pranshu Mohindra
- Department of Radiation Oncology, University of Maryland School of Medicine and Maryland Proton Treatment Center, Baltimore, MD, USA
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Radical Hemithoracic Radiotherapy Versus Palliative Radiotherapy in Non-metastatic Malignant Pleural Mesothelioma: Results from a Phase 3 Randomized Clinical Trial. Int J Radiat Oncol Biol Phys 2020; 109:1368-1376. [PMID: 33259933 DOI: 10.1016/j.ijrobp.2020.11.057] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 11/13/2020] [Accepted: 11/21/2020] [Indexed: 12/23/2022]
Abstract
PURPOSE We conducted a phase 3 randomized clinical trial to assess whether radical hemithoracic radiation therapy (RHR) compared with palliative radiation therapy (PR) can achieve overall survival (OS) advantages in patients with malignant pleural mesothelioma (MPM). METHODS AND MATERIALS From August 2014 to May 2018, patients with histologically diagnosed nonmetastatic MPM, who underwent nonradical lung-sparing surgery and chemotherapy (CHT), were randomly assigned (1:1) to receive RHR or PR. RHR total dose to the involved pleural cavity was 50 Gy in 25 fractions, and the gross residual disease received a simultaneous integrated boost of 60 Gy. The primary endpoint was OS. Secondary endpoints were local control, distant metastasis-free survival, progression-free survival, and acute and late toxicity rates. A sample size of 108 patients considering a type I error (α) of 0.05 and a statistical power of 80% was calculated to prove that RHR could improve the 2-year OS. OS was estimated with the Kaplan-Meier method and the log-rank test (2-sided) tested differences between arms. The univariate and multivariate analyses were performed using Cox proportional hazard model. Possible prognostic factors investigated: age, sex, performance status, lung surgery, gross residual disease, and histology. RESULTS One hundred eight patients were randomized: 53 to the PR arm and 55 to the RHR arm. Median follow-up was 14.6 months. The 2-year OS rate was 58% in the RHR arm versus 28% in the PR arm (hazard ratio, 0.54; 95% confidence interval, 0.31-0.95; P = .031). In the RHR arm: 11 patients experienced acute toxicity grade ≥3, 17 patients had grade 3 to 4 late toxicity. Nine patients experience a grade ≥2 pneumonitis, including 1 patient with grade 5. CONCLUSIONS RHR significantly improves survival in patients with MPM treated with nonradical lung-sparing surgery and CHT compared with palliative treatments, although it is associated with a nonnegligible toxicity profile.
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Patel R, Ludmir EB, Miccio JA, Menon H, Barsky AR, Mesko SM, Kodali M, Lautenschlaeger T, Adeberg S, Simone CB, Verma V. Disease-Related Outcomes and Toxicities of Intensity Modulated Radiation Therapy After Lung-Sparing Pleurectomy for Malignant Pleural Mesothelioma: A Systematic Review. Pract Radiat Oncol 2020; 10:423-433. [PMID: 32088429 DOI: 10.1016/j.prro.2020.02.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Revised: 01/06/2020] [Accepted: 02/08/2020] [Indexed: 12/15/2022]
Abstract
PURPOSE This review explores the use of intensity modulated radiation therapy (IMRT) after lung-sparing surgery in malignant pleural mesothelioma (MPM). Because severe toxicities have been documented after radiation therapy for MPM, its use remains controversial, especially as modern surgical management has shifted toward lung-sparing pleurectomy/decortication. IMRT is an advanced technique that may allow for safer radiation therapy delivery, but there remains limited data (including no summative data) to support this notion. METHODS AND MATERIALS We performed a systematic review evaluating the safety and efficacy of post-pleurectomy IMRT (P-IMRT). A systematic review of PubMed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted for publications of all dates that specifically reported clinical outcomes and/or toxicities of P-IMRT in patients with MPM. Ten original studies were included in this review. RESULTS The incidence of grade 3 pneumonitis ranged from 0% to 16%, with all but 2 studies reporting rates below 9%. Grade 4 and 5 pneumonitis were observed in less than 1.5% of cases, except in one publication that used hypofractionated radiation therapy to doses >60 Gy. Crude local failure rates ranged from 19% to 60%, median progression free survival ranged from 12 to 16 months, and median overall survival ranged from 19 to 28 months. CONCLUSIONS P-IMRT produces relatively few higher-grade toxicities and has reasonable disease-related outcomes, especially when delivered using conventionally fractionated regimens to doses of 45 to 54 Gy and exercising careful attention to dose constraints during treatment planning. IMRT can thus be considered in well-selected patients in whom adequate survival after pleurectomy is expected. These data also support the initiation of the phase III NRG-LU006 trial of extended pleurectomy/decortication and chemotherapy with or without IMRT.
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Affiliation(s)
| | - Ethan B Ludmir
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Joseph A Miccio
- Department of Therapeutic Radiology, Yale University, New Haven, Connecticut
| | - Hari Menon
- University of Arizona College of Medicine, Phoenix, Phoenix, Arizona
| | - Andrew R Barsky
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania
| | - Shane M Mesko
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Manya Kodali
- Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania
| | - Tim Lautenschlaeger
- Department of Radiation Oncology, Indiana University School of Medicine, Indianapolis, Indiana
| | - Sebastian Adeberg
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany
| | - Charles B Simone
- Department of Radiation Oncology, New York Proton Center, New York, New York
| | - Vivek Verma
- Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, Pennsylvania.
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Arrieta O, Lozano-Ruiz F, Blake-Cerda M, Catalán R, Lara-Mejía L, Salinas MÁ, Maldonado-Magos F, Corona-Cruz JF. Locoregional control and toxicity after pleurectomy/decortication and intensity-modulated pleural radiation therapy in patients with malignant pleural mesothelioma. Thorac Cancer 2020; 11:3448-3455. [PMID: 33030313 PMCID: PMC7705616 DOI: 10.1111/1759-7714.13668] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 09/03/2020] [Accepted: 09/03/2020] [Indexed: 12/03/2022] Open
Abstract
Background Treatment of malignant pleural mesothelioma (MPM) represents a major challenge for oncologists. Multimodality treatment, which generally involves induction chemotherapy, surgery and radiotherapy have recently shown promising results. The aim of this study was to evaluate the locoregional control and toxicity of intensity modulated radiotherapy (IMRT) after pleurectomy and decortication (P/D) as part of trimodality therapy for patients with locally advanced MPM. Methods We prospectively analyzed data from 20 patients with MPM treated at a single tertiary‐care institution. Initially every patient received induction chemotherapy with platinum‐based chemotherapy. After chemotherapy, patients without progression underwent P/D, and if feasible, hemi‐thoracic IMRT was administered at a planned dose of 50.4–54 Gy in 28–30 fractions and treated with 9–11 noncoplanar fields. Results A total of 15 of the 20 enrolled patients underwent P/D followed by IMRT to the hemi‐thoracic cavity. The median total radiotherapy dose was 48.7 Gy (23.4–54 Gy). Radiation pneumonitis (RP) developed in nine patients (60%), and of these, two patients (13.3%) experienced G3 or G4 RP. The estimated locoregional‐relapse‐free survival at two years was 75.9%, and the main pattern of recurrence was distant (72.7%). For the entire cohort median follow‐up was 22.7 months, median progression‐free survival was 18.9 months and median overall survival 23.6 months. Conclusions Platinum‐based chemotherapy followed by lung‐sparing surgery (P/D) and IMRT is a feasible and safe treatment modality that yields acceptable locoregional control in patients with locally advanced MPM; however, these results should be corroborated in larger studies.
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Affiliation(s)
- Oscar Arrieta
- Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, Mexico
| | - Francisco Lozano-Ruiz
- Radiation Oncology Department, Instituto Nacional de Cancerología (INCan), México City, Mexico
| | - Monika Blake-Cerda
- Radiation Oncology Department, Instituto Nacional de Cancerología (INCan), México City, Mexico
| | - Rodrigo Catalán
- Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, Mexico
| | - Luis Lara-Mejía
- Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, Mexico
| | - Miguel Ángel Salinas
- Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), México City, Mexico
| | | | - José F Corona-Cruz
- Thoracic Surgery Department, Instituto Nacional de Cancerología (INCan), México City, Mexico
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Thompson AB, Quinn TJ, Siddiqui ZA, Almahariq MF, Grills IS, Stevens CW. Addition of radiotherapy to surgery and chemotherapy improves survival in localized malignant pleural mesothelioma: A Surveillance, Epidemiology, and End Results (SEER) study. Lung Cancer 2020; 146:120-126. [PMID: 32531717 DOI: 10.1016/j.lungcan.2020.05.032] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2020] [Revised: 04/23/2020] [Accepted: 05/22/2020] [Indexed: 01/29/2023]
Abstract
INTRODUCTION Malignant pleural mesothelioma (MPM) is a devastating disease with poor survival outcomes for most patients. Optimizing therapeutic approaches is thus vital, but has been hampered by a dearth of randomized trials to guide decision making. We used a population-level database to evaluate the impact of radiotherapy as a component of trimodality therapy on overall survival (OS) in MPM. METHODS We retrospectively reviewed the SEER Radiation/Chemotherapy database for patients with MPM who received surgery and chemotherapy, with or without radiotherapy. A propensity score-matched analysis with inverse probability of treatment weighting (IPTW) was performed. Weight-adjusted univariate KM analysis was performed and doubly robust, IPTW-adjusted multivariable cox proportional hazards regression modeling was also performed to quantify the effect of radiotherapy on OS in trimodality therapy for MPM. RESULTS 1015 patients were identified. 678 patients received surgery and chemotherapy, and 337 patients received trimodality therapy. For patients with localized disease, OS was significantly improved with trimodality therapy (HR 0.56, CI 0.4 - 0.8, p = 0.001), which persisted with IPTW adjustment (HR 0.65, CI 0.49 - 0.95, p = 0.0248). No significant benefit was seen for patients with regional or distant disease. On multivariate analysis, positive predictors of survival after IPTW adjustment were female sex, diagnosis after 2005, and left-sided disease. CONCLUSIONS These findings support a significant benefit to OS by incorporating radiotherapy as a component of trimodality therapy for patients with localized MPM compared to only surgery and chemotherapy. It does not provide a significant overall survival benefit for patients with regional or metastatic disease.
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Affiliation(s)
- Andrew B Thompson
- Department of Radiation Oncology, Beaumont Health, 3601 W 13 Mile Rd, Royal Oak, MI 48073, United States
| | - Thomas J Quinn
- Department of Radiation Oncology, Beaumont Health, 3601 W 13 Mile Rd, Royal Oak, MI 48073, United States
| | - Zaid A Siddiqui
- Department of Radiation Oncology, Beaumont Health, 3601 W 13 Mile Rd, Royal Oak, MI 48073, United States
| | - Muayad F Almahariq
- Department of Radiation Oncology, Beaumont Health, 3601 W 13 Mile Rd, Royal Oak, MI 48073, United States
| | - Inga S Grills
- Department of Radiation Oncology, Beaumont Health, 3601 W 13 Mile Rd, Royal Oak, MI 48073, United States
| | - Craig W Stevens
- Department of Radiation Oncology, Beaumont Health, 3601 W 13 Mile Rd, Royal Oak, MI 48073, United States.
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Schröder C, Opitz I, Guckenberger M, Stahel R, Weder W, Förster R, Andratschke N, Lauk O. Stereotactic Body Radiation Therapy (SBRT) as Salvage Therapy for Oligorecurrent Pleural Mesothelioma After Multi-Modality Therapy. Front Oncol 2019; 9:961. [PMID: 31616640 PMCID: PMC6775182 DOI: 10.3389/fonc.2019.00961] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Accepted: 09/10/2019] [Indexed: 12/23/2022] Open
Abstract
Introduction: Therapy options for patients with oligoprogressive malignant pleural mesothelioma (MPM) are limited. Stereotactic Body Radiotherapy (SBRT) may be a promising therapeutic option, as it delivers a localized ablative dose of radiation and therefore balances efficacy and treatment related toxicities. The intent of this retrospective analysis was to evaluate the feasibility of SBRT for limited pleural recurrences. Methods and Materials: This retrospective single-institution study is based on the 21 consecutive patients treated with hypofractionated radiotherapy for oligoprogressive MPM. Clinical and radiological data was collected at regular follow-up visits including toxicity, local control and survival. Results: At primary diagnosis, 57% of the patients presented with stage III disease. Initial treatment of MPM consisted of induction chemotherapy (n = 12) prior to a macroscopic complete resection (n = 18). Three patients received additional intracavitary chemotherapy and another three patients were treated with chemotherapy alone without another treatment at the time of first diagnosis. A total of 50 lesions in recurrent MPM were treated with SBRT. The median number of radiotherapy fractions was 5 (range 3–20) with a median dose per fraction of 5 Gy (range 2.5–12.5 Gy). The median total treatment dose was 30 Gy (20–50 Gy) with a median prescription isodose line (IDL) of 65% (65–100%). Median follow-up of all patients from diagnosis was 28 months (range 7–152 months). Analyzing all lesions separately, the 12-months-local control from SBRT was 73.5%. The median progression free survival (PFS) after SBRT was 6 months (range 0–21 months) and the median OS from first first SBRT was 29 months (range 0–61 months). Only one patients experienced above Grade 3 toxicities. Conclusion: This analysis demonstrates the feasibility of a SBRT approach for oligorecurrent MPM. SBRT was well-tolerated even after multiple repetitions and local control was high with a promising median OS.
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Affiliation(s)
- Christina Schröder
- Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland
| | - Isabelle Opitz
- Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
| | | | - Rolf Stahel
- Department of Medical Oncology, University Hospital Zurich, Zurich, Switzerland
| | - Walter Weder
- Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
| | - Robert Förster
- Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland
| | - Nicolaus Andratschke
- Department of Radiation Oncology, University Hospital Zurich, Zurich, Switzerland
| | - Olivia Lauk
- Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
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Volumetric Modulated Arc Therapy After Lung Sparing Surgery for Malignant Pleural Mesothelioma: A Single Institution Experience. Clin Lung Cancer 2019; 21:86-93. [PMID: 31563545 DOI: 10.1016/j.cllc.2019.08.008] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2019] [Revised: 06/04/2019] [Accepted: 08/27/2019] [Indexed: 12/25/2022]
Abstract
INTRODUCTION We investigated the possible role of volumetric modulated arc therapy (VMAT) in the setting of adjuvant treatment of malignant pleural mesothelioma (MPM) after lung-sparing surgery with pleurectomy and decortication. MATERIALS AND METHODS Patients affected by MPM who had undergone pleurectomy and decortication and adjuvant radiotherapy with VMAT were included. The endpoints of the present analysis were local control, progression-free survival, and overall survival. Assessment of the variables affecting survival was performed using univariate and multivariate Cox proportional hazard models. RESULTS A total of 49 patients were included in the present study. Of the 49 patients, 96% had been treated with a trimodality approach. Radiotherapy was delivered to a median dose of 44 Gy in 22 fractions (range, 22-59.4 Gy). The treatment was well tolerated, with just 2 grade 3 acute toxicities, 1 grade 5, and 2 grade 4 toxicities recorded during the follow-up period. The median follow-up period was 27.4 months. The local control rate at 12, 24, and 36 months was 75.2%, 67.4%, and 56.5%, respectively. The median progression-free survival was 14.9 months (95% confidence interval [CI], 7.5-25.2). The median overall survival was 21.5 months (95% CI, 15.3-37.1). On multivariate analysis, the administration of carboplatin- instead of cisplatin-based chemotherapy (hazard ratio, 2.97; 95% CI, 1.22-7.26; P = .017) and R2 resection (hazard ratio, 1.95; 95% CI, 1.27-2.99; P = .002) showed a negative correlation with overall survival. On univariate analysis, the percentage of the heart receiving >20 Gy and >30 was associated with the occurrence of late pneumonitis (P = .018 and P = .077). CONCLUSION VMAT is feasible in the setting of MPM after lung-sparing surgery. The toxicity rates were reduced with this technique compared with historical data of older techniques. Local and distant failure remain a major issue to be addressed in future trials.
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Commentary: Return to intended radiation therapy-Criteria for resection? J Thorac Cardiovasc Surg 2019; 158:930-931. [PMID: 31160109 DOI: 10.1016/j.jtcvs.2019.04.050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2019] [Accepted: 04/12/2019] [Indexed: 10/26/2022]
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15
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Nelson DB, Rice DC, Mitchell KG, Tsao AS, Gomez DR, Sepesi B, Mehran RJ. Return to intended oncologic treatment after surgery for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2019; 158:924-929. [PMID: 31430846 DOI: 10.1016/j.jtcvs.2019.02.129] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2018] [Revised: 02/12/2019] [Accepted: 02/22/2019] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Trimodality therapy may prolong survival for patients with resectable malignant pleural mesothelioma. However, many patients are unable to complete therapy. We sought to identify risk factors for failing to complete adjuvant intensity-modulated radiation therapy after cytoreduction for malignant pleural mesothelioma. METHODS We performed a single-institution review of those who received an extrapleural pneumonectomy or pleurectomy/decortication for malignant pleural mesothelioma from 2004 to 2017. Multivariable logistic regression was used to assess preoperative or intraoperative risk factors associated with failing to complete adjuvant intensity-modulated radiation therapy. RESULTS A total of 160 patients were identified, among whom 94 (59%) received an extrapleural pneumonectomy and 66 (41%) received a pleurectomy/decortication. Adjuvant intensity-modulated radiation therapy was completed among 105 patients (66%). Reasons for failing to complete adjuvant intensity-modulated radiation therapy included mortality (19), dose constraints (21), postoperative morbidity or delayed recovery (11), and refused or unknown status (4). On multivariable analysis, American Society of Anesthesiologists 3+ classification (P = .002) and smoking history (P = .022) were associated with failure to complete adjuvant intensity-modulated radiation therapy, whereas forced expiratory volume in 1 second 70% or less of predicted and pStage 4 (T4) were significant on univariable analysis only. Other factors, including extrapleural pneumonectomy or pleurectomy/decortication, margin status, age, and histology, were not associated with receiving adjuvant intensity-modulated radiation therapy. CONCLUSIONS Many patients are unable to complete adjuvant intensity-modulated radiation therapy after cytoreduction. Failure to complete adjuvant intensity-modulated radiation therapy was associated with worse preoperative comorbidity, but not the type of surgery or margin status.
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Affiliation(s)
- David B Nelson
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Tex
| | - David C Rice
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Kyle G Mitchell
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Anne S Tsao
- Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Daniel R Gomez
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Boris Sepesi
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Tex
| | - Reza J Mehran
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Tex.
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Nelson DB, Rice DC, Mitchell KG, Tsao AS, Vaporciyan AA, Antonoff MB, Hofstetter WL, Walsh GL, Swisher SG, Roth JA, Gomez DR, Mehran RJ, Sepesi B. Defining the role of adjuvant radiotherapy for malignant pleural mesothelioma: a propensity-matched landmark analysis of the National Cancer Database. J Thorac Dis 2019; 11:1269-1278. [PMID: 31179069 DOI: 10.21037/jtd.2019.04.27] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Background Multimodality therapy may prolong survival among resectable malignant pleural mesothelioma (MPM). However, the role of adjuvant radiation remains controversial. We explored a large nationwide database to determine whether adjuvant radiation is associated with improved survival. Methods The National Cancer Database (NCDB) was queried to identify patients with MPM who received cancer-directed surgery between 2004-2013. Adjuvant radiation included intensity modulated radiation therapy or conformal 3D radiation. Propensity matching was performed with a 150-day landmark to address survivorship bias. Cox regression was used with an interaction term between pathologic stage and radiation. Results A total of 2,846 patients were identified as having undergone cancer-directed surgery for MPM; among whom 213 (7%) received adjuvant radiation. Adjuvant radiation was associated with improved survival among those who were stage I-II (P=0.024), but not stage III or IV (P=0.890 and P=0.183, respectively). After propensity matching, adjuvant radiation was associated with improved survival for those who were stage I-II [hazard ratio (HR) 0.52, P=0.035], whereas no similar effect was observed for those who were stage III or IV (P=0.190 and P=0.562, respectively). Multivariable regression revealed that sarcomatoid histology (HR 1.80, P=0.018) and stage IV disease (HR 1.65, P=0.033) were also associated with worse survival. Conclusions Adjuvant radiation was associated with improved survival among those with pathologic stage I-II MPM. No survival advantage was observed for those with pathologic stage III or stage IV MPM, however. Our results justify the need for further prospective trials to investigate the utility of adjuvant radiotherapy among those with MPM.
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Affiliation(s)
- David B Nelson
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer, Houston, TX, USA
| | - David C Rice
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer, Houston, TX, USA
| | - Kyle G Mitchell
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer, Houston, TX, USA
| | - Anne S Tsao
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer, Houston, TX, USA
| | - Ara A Vaporciyan
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer, Houston, TX, USA
| | - Mara B Antonoff
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer, Houston, TX, USA
| | - Wayne L Hofstetter
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer, Houston, TX, USA
| | - Garrett L Walsh
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer, Houston, TX, USA
| | - Stephen G Swisher
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer, Houston, TX, USA
| | - Jack A Roth
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer, Houston, TX, USA
| | - Daniel R Gomez
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer, Houston, TX, USA
| | - Reza J Mehran
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer, Houston, TX, USA
| | - Boris Sepesi
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer, Houston, TX, USA
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Leitzen C, Wilhelm-Buchstab T, Stumpf S, Heimann M, Koch D, Schmeel C, Simon B, Vornholt S, Garbe S, Röhner F, Schoroth F, Schild HH, Schüller H, Müdder T. Tomotherapy in malignant mesothelioma: a planning study to establish dose constraints. Strahlenther Onkol 2019; 195:668-676. [PMID: 30915490 DOI: 10.1007/s00066-019-01458-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2018] [Accepted: 03/14/2019] [Indexed: 01/15/2023]
Abstract
PURPOSE A planning study was performed for helical tomotherapy treatment. We evaluated the maximum achievable protection of organs at risk (OARs) in patients with malignant pleural mesothelioma after pleurectomy with simultaneous optimal target coverage. MATERIALS AND METHODS The datasets of 13 patients were included. The applied dose to the planning target volume (PTV) was 50.4 Gy with single doses of 1.8 Gy per fraction. Presuming optimal target coverage, we evaluated the applied dose to the OARs with special regard to the contralateral lung. RESULTS For left-(lsRT)/right(rsRT)-sided radiotherapy, target coverage for the PTV showed a D98 (mean) of 49.37/49.71 Gy (98.0%/98.6%) and a D2 (mean) of 54.19/54.61 Gy (107.5%/108.3%). The beam-on time was kept below 15 min. The achieved mean dose (D50) to the contralateral lung was kept below 4 Gy for lsRT and rsRT. With regard to the other organs at risk the applied doses were as follows: mean dose (lsRT): ipsilateral kidney (Dmean) 13.03 (5.32-22.18) Gy, contralateral kidney (Dmean) <2.0 Gy, heart (Dmean) 22.23 (13.57-27.72) Gy, spinal cord D1 <Gy; mean dose (rsRT): ipsilateral kidney (Dmean) 10.22 (6.30-18.04) Gy, contralateral kidney (Dmean) <2.1 Gy, heart (Dmean) 8.02 (6.0-10.38) Gy, spinal cord D1 <35.5 Gy. CONCLUSION With helical tomotherapy, postoperative treatment for malignant pleural mesothelioma after pleurectomy achieves good target coverage combined with simultaneous dose sparing to the (especially contralateral) OARs.
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Affiliation(s)
- Christina Leitzen
- Radiologische Klinik, FE Strahlentherapie, Universitätsklinik Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
| | - Timo Wilhelm-Buchstab
- Radiologische Klinik, FE Strahlentherapie, Universitätsklinik Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
| | - Sabina Stumpf
- Radiologische Klinik, FE Strahlentherapie, Universitätsklinik Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
| | - Martina Heimann
- Radiologische Klinik, FE Strahlentherapie, Universitätsklinik Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
| | - David Koch
- Radiologische Klinik, FE Strahlentherapie, Universitätsklinik Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
| | - Christopher Schmeel
- Radiologische Klinik, FE Strahlentherapie, Universitätsklinik Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
| | - Birgit Simon
- Radiologische Klinik, FE Strahlentherapie, Universitätsklinik Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
| | - Susanne Vornholt
- Radiologische Klinik, FE Strahlentherapie, Universitätsklinik Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
| | - Stephan Garbe
- Radiologische Klinik, FE Strahlentherapie, Universitätsklinik Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
| | - Fred Röhner
- Radiologische Klinik, FE Strahlentherapie, Universitätsklinik Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
| | - Felix Schoroth
- Radiologische Klinik, FE Strahlentherapie, Universitätsklinik Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
| | - Hans Heinz Schild
- Radiologische Klinik, FE Strahlentherapie, Universitätsklinik Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
| | - Heinrich Schüller
- Radiologische Klinik, FE Strahlentherapie, Universitätsklinik Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
| | - Thomas Müdder
- Radiologische Klinik, FE Strahlentherapie, Universitätsklinik Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany
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Computed tomography features of local pleural recurrence in patients with malignant pleural mesothelioma treated with intensity-modulated pleural radiation therapy. Eur Radiol 2019; 29:3696-3704. [PMID: 30689034 DOI: 10.1007/s00330-018-5937-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 10/11/2018] [Accepted: 11/29/2018] [Indexed: 10/27/2022]
Abstract
OBJECTIVE This study was conducted in order to describe the computed tomography (CT) features of local pleural recurrence in patients with malignant pleural mesothelioma undergoing intensity-modulated pleural radiation therapy (IMPRINT) as part of multimodality treatment. METHODS In this observational study, 58 patients treated with IMPRINT between September 21, 2004, and December 1, 2014 were included. Baseline and follow-up CT scans were qualitatively assessed. On follow-up scans, pleural thickening was categorized as unchanged, decreased, or new/increased. New/increased pleural abnormality was subcategorized as diffuse smooth pleural thickening, diffuse nodular pleural thickening, focal pleural nodule, or multiple pleural nodules. To identify features more frequently present at the time of local recurrence, follow-up scans with local recurrence were matched to four control scans; exact conditional logistic regression was performed. RESULTS Twenty-one (36%) patients had local pleural recurrence and 20 (34%) patients had nonpleural recurrence; 3 patients had both types of recurrence. The 1-year cumulative incidence rate of local recurrence was 27% (95% confidence interval 15, 39). On follow-up scans, three patterns of pleural abnormality were significantly associated with local recurrence: new/increased multiple pleural nodules (10 (48%) positive scans vs 0 control scans), new/increased diffuse nodular pleural thickening (7 (33%) positive scans vs 1 (1%) control scans), and new/increased focal pleural nodule (3 (14%) positive scans vs 1 (1%) control scan) (p < 0.001 for all). CONCLUSIONS Multiple new/increased pleural nodules are the feature most commonly present at local recurrence following IMPRINT; however, any pattern of increased nodular pleural thickening is suspicious. KEY POINTS • In patients with mesothelioma receiving intensity-modulated pleural radiation as part of multimodality therapy, increasing multiple pleural nodules is the computed tomography feature most commonly present at local recurrence. • In these patients, any CT pattern of increased nodular pleural thickening should be considered suspicious for local recurrence. • The most common sites of nonpleural recurrence were lung parenchyma, thoracic lymph nodes, and peritoneum.
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Radiation Therapy in Mesothelioma. Radiat Oncol 2019. [DOI: 10.1007/978-3-319-52619-5_36-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022] Open
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De Bondt C, Psallidas I, Van Schil PEY, van Meerbeeck JP. Combined modality treatment in mesothelioma: a systemic literature review with treatment recommendations. Transl Lung Cancer Res 2018; 7:562-573. [PMID: 30450295 DOI: 10.21037/tlcr.2018.10.02] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
In spite of recent progress, malignant pleural mesothelioma (MPM) remains synonymous with poor prognosis. A selected minority (<10%) of patients is eligible for a radical treatment with a combination of systemic chemotherapy (CT) and/or surgery and/or radiotherapy (RT), in an effort to maintain locoregional tumor control after achieving a macroscopically complete resection (MCR). However, as of yet there is no standard of care for this so-called multimodality treatment. As its potential gain is still limited (approximately one year added to overall survival), we must balance its efficacy with its cumulative toxicity. Several combined modality treatment trials are currently ongoing using novel techniques in surgery, RT and/or CT in an attempt to reduce the morbidity and mortality associated with older multimodality treatment protocols. Guidelines are following suit and are now including or mentioning this treatment option. In this systematic review, we analyze the available data in order to address the following questions: Is combined modality better than single modality? What is the optimal regimen within each modality? What is the optimal sequence of combined modality?
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Affiliation(s)
- Charlotte De Bondt
- Department Pulmonology and Thoracic Oncology, Antwerp University and Antwerp University Hospital, Antwerp, Belgium
| | - Ioannis Psallidas
- Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Paul E Y Van Schil
- Department Thoracic and Vascular Surgery, Antwerp University and Antwerp University Hospital, Antwerp, Belgium
| | - Jan P van Meerbeeck
- Department Pulmonology and Thoracic Oncology, Antwerp University and Antwerp University Hospital, Antwerp, Belgium
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Fodor A, Broggi S, Incerti E, Dell'Oca I, Fiorino C, Samanes Gajate AM, Pasetti M, Cattaneo MG, Passoni P, Gianolli L, Calandrino R, Picchio M, Di Muzio N. Moderately Hypofractionated Helical IMRT, FDG-PET/CT-guided, for Progressive Malignant Pleural Mesothelioma in Patients With Intact Lungs. Clin Lung Cancer 2018; 20:e29-e38. [PMID: 30253920 DOI: 10.1016/j.cllc.2018.08.019] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2018] [Revised: 08/21/2018] [Accepted: 08/29/2018] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The objective of this study was to present the outcomes of moderately hypofractionated helical intensity-modulated radiation therapy (HT) with/without simultaneous integrated boost (SIB) on fluorodeoxyglucose-positron emission tomography (FDG-PET) positive areas (gross tumor volume [GTV]-PET) for patients with progressive malignant pleural mesothelioma (MPM) after previous treatments. METHODS AND MATERIALS From May 2006 to April 2014, 51 patients with a median age of 68.8 years (range, 38.6-82 years) were treated. There were 41 men and 10 women; 43 epithelioid MPM and 8 sarcomatoid, involving the left pleura in 25 patients and the right pleura in 26 patients. The initial stage was: I, 11 patients; II, 14 patients; III, 17 patients; and IV, 9 patients. Chemotherapy was prescribed for 46 patients, for 6 cycles (range, 0-18 cycles). Eighteen patients had pleurectomy/decortication, and 33 had talc pleurodesis. FDG-PET was used for target identification. A median dose of 56 Gy/25 fractions was prescribed to the involved pleura, and SIB to 62.5 Gy to GTV-PET was added in 38 patients. RESULTS The median survival from diagnosis was 25.8 months (range, 8.4-99.0 months). One patient, treated with SIB, was alive at the October 2017 follow-up. Two cases of grade 5 radiation pneumonitis were registered. A GTV-PET ≤ 205 cc was predictive of late ≥ grade 2 lung toxicity, but also of better survival in stage III and IV disease: 5.9 versus 11.7 months (P = .04). A GTV-PET ≥ 473 cc was predictive of early death (P = .001). CONCLUSIONS Moderately hypofractionated, FDG-PET guided salvage HT in patients with progressive MPM after previous treatments showed acceptable toxicity and outcome results similar to adjuvant radiotherapy after pleurectomy/decortication, suggesting that the delay of radiotherapy is not detrimental to survival, and has the associated benefit of postponing inherent toxicity.
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Affiliation(s)
- Andrei Fodor
- Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy.
| | - Sara Broggi
- Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy
| | - Elena Incerti
- Department of Nuclear Medicine, San Raffaele Scientific Institute, Milan, Italy
| | - Italo Dell'Oca
- Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy
| | - Claudio Fiorino
- Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy
| | | | - Marcella Pasetti
- Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy
| | - Mauro G Cattaneo
- Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy
| | - Paolo Passoni
- Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy
| | - Luigi Gianolli
- Department of Nuclear Medicine, San Raffaele Scientific Institute, Milan, Italy
| | - Riccardo Calandrino
- Department of Medical Physics, San Raffaele Scientific Institute, Milan, Italy
| | - Maria Picchio
- Department of Nuclear Medicine, San Raffaele Scientific Institute, Milan, Italy; Faculty of Medicine and Surgery, Vita-Salute San Raffaele University, Milan, Italy
| | - Nadia Di Muzio
- Department of Radiotherapy, San Raffaele Scientific Institute, Milan, Italy
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Cramer G, Simone CB, Busch TM, Cengel KA. Adjuvant, neoadjuvant, and definitive radiation therapy for malignant pleural mesothelioma. J Thorac Dis 2018; 10:S2565-S2573. [PMID: 30206500 DOI: 10.21037/jtd.2018.07.65] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
While ionizing radiotherapy (RT) can provide durable local control, the relative radiosensitivity of surrounding organs such as the lungs and heart and the distributed nature of the pleura limit the ability to safely deliver RT for patients with malignant pleural mesothelioma (MPM). Recent advances in the technological sophistication of RT planning and delivery devices have resulted in increased spatial control of irradiation dose that has extended the palliative and definitive applications of RT for patients with MPM. This review will outline the logistical, mechanistic and clinical basics of RT and the clinical trials supporting the use of RT in the multidisciplinary care of patients with MPM.
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Affiliation(s)
- Gwendolyn Cramer
- Department of Radiation Oncology, Hospital of the University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
| | - Charles B Simone
- Department of Radiation Oncology, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Theresa M Busch
- Department of Radiation Oncology, Hospital of the University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
| | - Keith A Cengel
- Department of Radiation Oncology, Hospital of the University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA
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Shaaban SG, Verma V, Choi JI, Shabason J, Sharma S, Glass E, Grover S, Badiyan SN, Simone CB. Utilization of Intensity-Modulated Radiation Therapy for Malignant Pleural Mesothelioma in the United States. Clin Lung Cancer 2018; 19:e685-e692. [PMID: 29803576 DOI: 10.1016/j.cllc.2018.04.019] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2018] [Revised: 04/04/2018] [Accepted: 04/26/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Although postoperative radiotherapy (RT) for malignant pleural mesothelioma (MPM) has historically been delivered using 3-dimensional conformal RT (3DCRT) techniques, multiple reports show noteworthy safety and efficacy of the more advanced intensity-modulated RT (IMRT). To our knowledge, this is the only known study to evaluate national practice patterns of IMRT utilization for MPM. MATERIALS AND METHODS The National Cancer Data Base was queried for newly-diagnosed MPM patients who underwent definitive surgery (extrapleural pneumonectomy [EPP] or extended pleurectomy/decortication [P/D]) followed by adjuvant RT. Patients with metastatic disease, non-EPP or P/D surgical techniques, and lack of RT receipt (or without specified RT technique) were excluded. Statistics included multivariable logistic regression, Kaplan-Meier overall survival (OS) analysis, and Cox proportional hazards modeling. RESULTS Overall, 286 patients met criteria (181 [63%] IMRT and 105 [37%] 3DCRT). Temporal trends revealed that although 3DCRT was more common at initial time periods, IMRT utilization rose from 2004 to 2007 and stayed as a relatively constant majority thereafter. This was also present when substratifying the cohort according to EPP versus P/D approaches. IMRT was more often delivered at academic centers, along with institutions in the Southern United States, whereas 3DCRT was more frequently utilized in community facilities and in the Northeast (P ≤ .05 for all). RT technique did not affect OS (P > .05 for all comparisons). CONCLUSION In the United States, IMRT is now the most commonly utilized adjuvant RT technique for MPM. Facility and regional differences might associate with IMRT delivery. The findings of this investigation have implications for insurance coverage, clinical referral patterns, and ongoing and future prospective trial design.
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Affiliation(s)
- Sherif G Shaaban
- Department of Radiation Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX
| | - Vivek Verma
- Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE
| | - J Isabelle Choi
- Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD
| | - Jacob Shabason
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA
| | - Sonam Sharma
- Department of Radiation Oncology, The Mount Sinai Hospital, New York, NY
| | - Erica Glass
- California Protons Cancer Therapy Center, San Diego, CA
| | - Surbhi Grover
- Department of Radiation Oncology, University of Pennsylvania, Philadelphia, PA
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Spatola C, Militello C, Tocco A, Salamone V, Luigi R, Migliore M, Marletta D, Cannizzaro A, Bevilacqua R, Milone P, Pergolizzi S, Privitera G. Single-institution experience of intensity-modulated radiotherapy for malignant pleural mesothelioma at University of Catania. Future Oncol 2018; 14:17-21. [PMID: 29400553 DOI: 10.2217/fon-2017-0280] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
AIM The multimodal approach to malignant pleural mesothelioma is gradually becoming the standard of care for this disease in patients with good performance status. Materials & methods: We report our experience concerning eight cases treated with the use of static step-and-shoot intensity-modulated radiotherapy to the whole pleural cavity, in patients already undergoing surgical and/or antiblastic therapy. Results & conclusion: Results at a median follow-up of 16 months showed a median survival from the initial treatment of 29 months, with lung toxicity of grade II reported only in two patients.
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Affiliation(s)
- Corrado Spatola
- Unità Operativa Complessa Radiodiagnostica e Radioterapia, AOU Policlinico-VE, Catania 95125, Italy
| | - Carmelo Militello
- Unità Operativa Complessa Radiodiagnostica e Radioterapia, AOU Policlinico-VE, Catania 95125, Italy
| | - Alessandra Tocco
- Unità Operativa Complessa Radiodiagnostica e Radioterapia, AOU Policlinico-VE, Catania 95125, Italy
| | - Vincenzo Salamone
- Unità Operativa Complessa Radiodiagnostica e Radioterapia, AOU Policlinico-VE, Catania 95125, Italy
| | - Raffaele Luigi
- Unità Operativa Complessa Radiodiagnostica e Radioterapia, AOU Policlinico-VE, Catania 95125, Italy
| | - Marcello Migliore
- Unità Operativa Complessa Chirurgia Toracica, AOU Policlinico-VE, Catania, Italy
| | - Dario Marletta
- Unità Operativa Complessa Radiodiagnostica e Radioterapia, AOU Policlinico-VE, Catania 95125, Italy
| | - Alessandra Cannizzaro
- Unità Operativa Complessa Radiodiagnostica e Radioterapia, AOU Policlinico-VE, Catania 95125, Italy
| | - Roberta Bevilacqua
- Unità Operativa Complessa Radiodiagnostica e Radioterapia, AOU Policlinico-VE, Catania 95125, Italy
| | - Pietro Milone
- Unità Operativa Complessa Radiodiagnostica e Radioterapia, AOU Policlinico-VE, Catania 95125, Italy
| | - Stefano Pergolizzi
- Unità Operativa Complessa Radioterapia, AOU Policlinico, Messina 98124, Italy
| | - Giuseppe Privitera
- Unità Operativa Complessa Radiodiagnostica e Radioterapia, AOU Policlinico-VE, Catania 95125, Italy
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Kindler HL, Ismaila N, Armato SG, Bueno R, Hesdorffer M, Jahan T, Jones CM, Miettinen M, Pass H, Rimner A, Rusch V, Sterman D, Thomas A, Hassan R. Treatment of Malignant Pleural Mesothelioma: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol 2018; 36:1343-1373. [PMID: 29346042 DOI: 10.1200/jco.2017.76.6394] [Citation(s) in RCA: 271] [Impact Index Per Article: 38.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Purpose To provide evidence-based recommendations to practicing physicians and others on the management of malignant pleural mesothelioma. Methods ASCO convened an Expert Panel of medical oncology, thoracic surgery, radiation oncology, pulmonary, pathology, imaging, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 1990 through 2017. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. Results The literature search identified 222 relevant studies to inform the evidence base for this guideline. Recommendations Evidence-based recommendations were developed for diagnosis, staging, chemotherapy, surgical cytoreduction, radiation therapy, and multimodality therapy in patients with malignant pleural mesothelioma. Additional information is available at www.asco.org/thoracic-cancer-guidelines and www.asco.org/guidelineswiki .
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Affiliation(s)
- Hedy L Kindler
- Hedy L. Kindler and Samuel G. Armato III, The University of Chicago, Chicago, IL; Nofisat Ismaila, American Society of Clinical Oncology; Mary Hesdorffer, Mesothelioma Applied Research Foundation, Alexandria, VA; Raphael Bueno, Harvard Medical School, Boston, MA; Thierry Jahan, University of California San Francisco, San Francisco, CA; Clyde Michael Jones, Baptist Cancer Center Physicians Foundation, Memphis, TN; Markku Miettinen, Anish Thomas and Raffit Hassan, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Harvey Pass and Daniel Sterman, New York University Langone Medical Center; and Andreas Rimner and Valerie Rusch, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Nofisat Ismaila
- Hedy L. Kindler and Samuel G. Armato III, The University of Chicago, Chicago, IL; Nofisat Ismaila, American Society of Clinical Oncology; Mary Hesdorffer, Mesothelioma Applied Research Foundation, Alexandria, VA; Raphael Bueno, Harvard Medical School, Boston, MA; Thierry Jahan, University of California San Francisco, San Francisco, CA; Clyde Michael Jones, Baptist Cancer Center Physicians Foundation, Memphis, TN; Markku Miettinen, Anish Thomas and Raffit Hassan, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Harvey Pass and Daniel Sterman, New York University Langone Medical Center; and Andreas Rimner and Valerie Rusch, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Samuel G Armato
- Hedy L. Kindler and Samuel G. Armato III, The University of Chicago, Chicago, IL; Nofisat Ismaila, American Society of Clinical Oncology; Mary Hesdorffer, Mesothelioma Applied Research Foundation, Alexandria, VA; Raphael Bueno, Harvard Medical School, Boston, MA; Thierry Jahan, University of California San Francisco, San Francisco, CA; Clyde Michael Jones, Baptist Cancer Center Physicians Foundation, Memphis, TN; Markku Miettinen, Anish Thomas and Raffit Hassan, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Harvey Pass and Daniel Sterman, New York University Langone Medical Center; and Andreas Rimner and Valerie Rusch, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Raphael Bueno
- Hedy L. Kindler and Samuel G. Armato III, The University of Chicago, Chicago, IL; Nofisat Ismaila, American Society of Clinical Oncology; Mary Hesdorffer, Mesothelioma Applied Research Foundation, Alexandria, VA; Raphael Bueno, Harvard Medical School, Boston, MA; Thierry Jahan, University of California San Francisco, San Francisco, CA; Clyde Michael Jones, Baptist Cancer Center Physicians Foundation, Memphis, TN; Markku Miettinen, Anish Thomas and Raffit Hassan, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Harvey Pass and Daniel Sterman, New York University Langone Medical Center; and Andreas Rimner and Valerie Rusch, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Mary Hesdorffer
- Hedy L. Kindler and Samuel G. Armato III, The University of Chicago, Chicago, IL; Nofisat Ismaila, American Society of Clinical Oncology; Mary Hesdorffer, Mesothelioma Applied Research Foundation, Alexandria, VA; Raphael Bueno, Harvard Medical School, Boston, MA; Thierry Jahan, University of California San Francisco, San Francisco, CA; Clyde Michael Jones, Baptist Cancer Center Physicians Foundation, Memphis, TN; Markku Miettinen, Anish Thomas and Raffit Hassan, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Harvey Pass and Daniel Sterman, New York University Langone Medical Center; and Andreas Rimner and Valerie Rusch, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Thierry Jahan
- Hedy L. Kindler and Samuel G. Armato III, The University of Chicago, Chicago, IL; Nofisat Ismaila, American Society of Clinical Oncology; Mary Hesdorffer, Mesothelioma Applied Research Foundation, Alexandria, VA; Raphael Bueno, Harvard Medical School, Boston, MA; Thierry Jahan, University of California San Francisco, San Francisco, CA; Clyde Michael Jones, Baptist Cancer Center Physicians Foundation, Memphis, TN; Markku Miettinen, Anish Thomas and Raffit Hassan, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Harvey Pass and Daniel Sterman, New York University Langone Medical Center; and Andreas Rimner and Valerie Rusch, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Clyde Michael Jones
- Hedy L. Kindler and Samuel G. Armato III, The University of Chicago, Chicago, IL; Nofisat Ismaila, American Society of Clinical Oncology; Mary Hesdorffer, Mesothelioma Applied Research Foundation, Alexandria, VA; Raphael Bueno, Harvard Medical School, Boston, MA; Thierry Jahan, University of California San Francisco, San Francisco, CA; Clyde Michael Jones, Baptist Cancer Center Physicians Foundation, Memphis, TN; Markku Miettinen, Anish Thomas and Raffit Hassan, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Harvey Pass and Daniel Sterman, New York University Langone Medical Center; and Andreas Rimner and Valerie Rusch, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Markku Miettinen
- Hedy L. Kindler and Samuel G. Armato III, The University of Chicago, Chicago, IL; Nofisat Ismaila, American Society of Clinical Oncology; Mary Hesdorffer, Mesothelioma Applied Research Foundation, Alexandria, VA; Raphael Bueno, Harvard Medical School, Boston, MA; Thierry Jahan, University of California San Francisco, San Francisco, CA; Clyde Michael Jones, Baptist Cancer Center Physicians Foundation, Memphis, TN; Markku Miettinen, Anish Thomas and Raffit Hassan, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Harvey Pass and Daniel Sterman, New York University Langone Medical Center; and Andreas Rimner and Valerie Rusch, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Harvey Pass
- Hedy L. Kindler and Samuel G. Armato III, The University of Chicago, Chicago, IL; Nofisat Ismaila, American Society of Clinical Oncology; Mary Hesdorffer, Mesothelioma Applied Research Foundation, Alexandria, VA; Raphael Bueno, Harvard Medical School, Boston, MA; Thierry Jahan, University of California San Francisco, San Francisco, CA; Clyde Michael Jones, Baptist Cancer Center Physicians Foundation, Memphis, TN; Markku Miettinen, Anish Thomas and Raffit Hassan, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Harvey Pass and Daniel Sterman, New York University Langone Medical Center; and Andreas Rimner and Valerie Rusch, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Andreas Rimner
- Hedy L. Kindler and Samuel G. Armato III, The University of Chicago, Chicago, IL; Nofisat Ismaila, American Society of Clinical Oncology; Mary Hesdorffer, Mesothelioma Applied Research Foundation, Alexandria, VA; Raphael Bueno, Harvard Medical School, Boston, MA; Thierry Jahan, University of California San Francisco, San Francisco, CA; Clyde Michael Jones, Baptist Cancer Center Physicians Foundation, Memphis, TN; Markku Miettinen, Anish Thomas and Raffit Hassan, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Harvey Pass and Daniel Sterman, New York University Langone Medical Center; and Andreas Rimner and Valerie Rusch, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Valerie Rusch
- Hedy L. Kindler and Samuel G. Armato III, The University of Chicago, Chicago, IL; Nofisat Ismaila, American Society of Clinical Oncology; Mary Hesdorffer, Mesothelioma Applied Research Foundation, Alexandria, VA; Raphael Bueno, Harvard Medical School, Boston, MA; Thierry Jahan, University of California San Francisco, San Francisco, CA; Clyde Michael Jones, Baptist Cancer Center Physicians Foundation, Memphis, TN; Markku Miettinen, Anish Thomas and Raffit Hassan, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Harvey Pass and Daniel Sterman, New York University Langone Medical Center; and Andreas Rimner and Valerie Rusch, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Daniel Sterman
- Hedy L. Kindler and Samuel G. Armato III, The University of Chicago, Chicago, IL; Nofisat Ismaila, American Society of Clinical Oncology; Mary Hesdorffer, Mesothelioma Applied Research Foundation, Alexandria, VA; Raphael Bueno, Harvard Medical School, Boston, MA; Thierry Jahan, University of California San Francisco, San Francisco, CA; Clyde Michael Jones, Baptist Cancer Center Physicians Foundation, Memphis, TN; Markku Miettinen, Anish Thomas and Raffit Hassan, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Harvey Pass and Daniel Sterman, New York University Langone Medical Center; and Andreas Rimner and Valerie Rusch, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Anish Thomas
- Hedy L. Kindler and Samuel G. Armato III, The University of Chicago, Chicago, IL; Nofisat Ismaila, American Society of Clinical Oncology; Mary Hesdorffer, Mesothelioma Applied Research Foundation, Alexandria, VA; Raphael Bueno, Harvard Medical School, Boston, MA; Thierry Jahan, University of California San Francisco, San Francisco, CA; Clyde Michael Jones, Baptist Cancer Center Physicians Foundation, Memphis, TN; Markku Miettinen, Anish Thomas and Raffit Hassan, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Harvey Pass and Daniel Sterman, New York University Langone Medical Center; and Andreas Rimner and Valerie Rusch, Memorial Sloan Kettering Cancer Center, New York, NY
| | - Raffit Hassan
- Hedy L. Kindler and Samuel G. Armato III, The University of Chicago, Chicago, IL; Nofisat Ismaila, American Society of Clinical Oncology; Mary Hesdorffer, Mesothelioma Applied Research Foundation, Alexandria, VA; Raphael Bueno, Harvard Medical School, Boston, MA; Thierry Jahan, University of California San Francisco, San Francisco, CA; Clyde Michael Jones, Baptist Cancer Center Physicians Foundation, Memphis, TN; Markku Miettinen, Anish Thomas and Raffit Hassan, Center for Cancer Research, National Cancer Institute, Bethesda, MD; Harvey Pass and Daniel Sterman, New York University Langone Medical Center; and Andreas Rimner and Valerie Rusch, Memorial Sloan Kettering Cancer Center, New York, NY
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de Perrot M, Wu L, Wu M, Cho BCJ. Radiotherapy for the treatment of malignant pleural mesothelioma. Lancet Oncol 2017; 18:e532-e542. [PMID: 28884702 DOI: 10.1016/s1470-2045(17)30459-x] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2017] [Revised: 06/06/2017] [Accepted: 06/08/2017] [Indexed: 12/21/2022]
Abstract
Malignant pleural mesothelioma is an aggressive disease that continues to be associated with poor outcomes. Although, traditionally this disease is considered to be resistant to radiotherapy, more recent evidence suggests that radiotherapy can produce positive outcomes. Over the past 15 years, the development of new, highly conformal radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), has enabled investigators to optimise the delivery of high-dose radiotherapy to the whole of the hemithorax. Prospective single-arm trials have shown that the median survival of patients who have completed high-dose hemithoracic radiotherapy after extrapleural pneumonectomy could reach 23·9-39·4 months independent of the chemotherapeutic response, suggesting that IMRT could potentially have an intrinsic benefit to this subset of patients. These observations have led to a change in practice, with the introduction of adjuvant pleural IMRT after pleurectomy-decortication and the development of induction-accelerated hemithoracic IMRT followed by extrapleural pneumonectomy. This Review focuses on recent observations on the role of radiotherapy in the treatment of malignant pleural mesothelioma, with particular emphasis on the results of clinical trials that evaluate the role of high-dose hemithoracic radiotherapy.
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Affiliation(s)
- Marc de Perrot
- Division of Thoracic Surgery, Princess Margaret Cancer Centre and Toronto General Hospital, University Health Network, University of Toronto, ON, Canada.
| | - Licun Wu
- Latner Thoracic Surgery Laboratories, Princess Margaret Cancer Centre and Toronto General Hospital, University Health Network, University of Toronto, ON, Canada
| | - Matthew Wu
- Latner Thoracic Surgery Laboratories, Princess Margaret Cancer Centre and Toronto General Hospital, University Health Network, University of Toronto, ON, Canada
| | - B C John Cho
- Department of Radiation Oncology, Princess Margaret Cancer Centre and Toronto General Hospital, University Health Network, University of Toronto, ON, Canada
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Foroudi F, Smith JG, Putt F, Wada M. High-dose palliative radiotherapy for malignant pleural mesothelioma. J Med Imaging Radiat Oncol 2017; 61:797-803. [DOI: 10.1111/1754-9485.12636] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 05/12/2017] [Indexed: 10/19/2022]
Affiliation(s)
- Farshad Foroudi
- Department of Radiation Oncology, Austin Health; Melbourne Victoria Australia
| | | | - Faye Putt
- Department of Radiation Oncology, Austin Health; Melbourne Victoria Australia
| | - Morikatsu Wada
- Department of Radiation Oncology, Austin Health; Melbourne Victoria Australia
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Marulli G, Faccioli E, Bellini A, Mammana M, Rea F. Induction chemotherapy vs post-operative adjuvant therapy for malignant pleural mesothelioma. Expert Rev Respir Med 2017; 11:649-660. [PMID: 28580813 DOI: 10.1080/17476348.2017.1338951] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Malignant pleural mesothelioma (MPM) is an aggressive neoplasia. Multidisciplinary treatments, including the association of induction and/or adjuvant therapeutic regimens with surgery, have been reported to give encouraging results. Current therapeutic options are not well standardized yet, especially regarding the best association between surgery and medical treatments. The present review aims to assess safety, efficacy and outcomes of different therapies for MPM. Areas covered: This article focuses on the multimodality treatment of mesothelioma. A systematic review was performed by using electronic databases to identify studies that considered induction and adjuvant approaches in MPM therapy in a multidisciplinary setting, including surgery. Endpoints included overall survival, disease free survival, disease recurrence, and complications. Expert commentary: This systematic review offers a comprehensive view of current multidisciplinary therapeutic strategies for MPM, suggesting that multimodality therapy offers acceptable outcomes with better results reported for trimodality approaches. Individualization of care for each patient is fundamental in choosing the most appropriate treatment. The growing complexity of treatment protocols mandates that MPM patients be referred to specialized Centers, in which every component of the interdisciplinary team can provide the necessary expertise and quality of care.
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Affiliation(s)
- Giuseppe Marulli
- a Thoracic Surgery Unit, Department of Cardiologic, Thoracic and Vascular Sciences , University of Padova , Padova , Italy
| | - Eleonora Faccioli
- a Thoracic Surgery Unit, Department of Cardiologic, Thoracic and Vascular Sciences , University of Padova , Padova , Italy
| | - Alice Bellini
- a Thoracic Surgery Unit, Department of Cardiologic, Thoracic and Vascular Sciences , University of Padova , Padova , Italy
| | - Marco Mammana
- a Thoracic Surgery Unit, Department of Cardiologic, Thoracic and Vascular Sciences , University of Padova , Padova , Italy
| | - Federico Rea
- a Thoracic Surgery Unit, Department of Cardiologic, Thoracic and Vascular Sciences , University of Padova , Padova , Italy
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Jhavar S, Pruszynski J, Gowan A, Boyle T, Deb N, Patel M. Intensity modulated radiation therapy after extra-pleural pneumonectomy for malignant pleural mesothelioma is feasible without fatal pulmonary toxicity and provides good survival. Asia Pac J Clin Oncol 2017; 14:e88-e94. [PMID: 28371288 DOI: 10.1111/ajco.12680] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2016] [Accepted: 02/02/2017] [Indexed: 11/30/2022]
Abstract
AIM To analyze patterns of failure, toxicity, relapse-free survival (RFS), and overall survival (OS) in malignant pleural mesothelioma (MPM) patients treated with intensity-modulated radiation therapy following extrapleural pneumonectomy (EPP). METHODS We reviewed 18 charts of patients with MPM from 2005 to 2014 who underwent EPP followed by hemithoracic intensity-modulated radiation therapy. Intensity-modulated radiation therapy dose delivery adhered to published lung dose constraints. Kaplan-Meier curves were used to assess the RFS and OS. Median survival times are reported for both RFS and OS. RESULTS Median age was 65 years (range: 40-76 years). Chemotherapy was administered in four neo-adjuvant and seven adjuvant patients. Pathological American Joint Committee on Cancer stages II, III, IV, surgical margin, lympho-vascular space, pericardium, and chest wall involvement were seen in 3, 12, 3, 9, 7, 12 and 3 patients, respectively. The majority of the patients received 45 Gy in 25 fractions. The mean lung dose was 7.14 Gy (range: 5 Gy-9.3 Gy). The mean V20 was 2.23%. At a median follow-up of 3 years, eight patients were alive (44%); 10 experienced relapse (56%). Median RFS and OS were 24.4 months (95% CI: >16.3 months) and 38.2 months (95% CI: 17.4-78.1 months), respectively. Acute toxicities were fatigue, dermatitis, nausea, esophagitis/dysphagia, cough, and dyspnea on exertion. No grade III, IV, or fatal pulmonary toxicities were observed. CONCLUSION Intensity-modulated radiation therapy following EPP for MPM resulted in RFS and OS comparable to the published literature without significant toxicity.
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Affiliation(s)
- Sameer Jhavar
- Department of Radiation Oncology, Baylor Scott and White Health, Temple, Texas, USA
| | | | - Alan Gowan
- Hematology and Oncology, Baylor Scott and White Health, Temple, Texas, USA
| | - Teresa Boyle
- Radiation Oncology, Austin Cancer Centers, Texas, USA
| | - Niloyjyoti Deb
- Department of Radiation Oncology, Baylor Scott and White Health, Temple, Texas, USA
| | - Mehul Patel
- Department of Radiation Oncology, Baylor Scott and White Health, Temple, Texas, USA
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Bertoglio P, Ambrogi MC, Chella A, Aprile V, Dini P, Korasidis S, Fanucchi O, Mussi A. Is less also better? A single-institution experience on treatment of early stage Malignant Pleural Mesothelioma. Eur J Surg Oncol 2017; 43:1365-1371. [PMID: 28274663 DOI: 10.1016/j.ejso.2017.02.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2016] [Revised: 01/07/2017] [Accepted: 02/12/2017] [Indexed: 12/13/2022] Open
Abstract
OBJECTIVES No clear evidence of which surgical procedure should be performed for early stage mesothelioma is available to date. We analyzed our 10-year experience in the treatment of early stage mesothelioma with surgery and Hyperthermic IntraTHOracic Chemotherapy. METHODS We retrospectively analyzed all cases of histologically proven epithelioid or biphasic IMIG stage I and II mesothelioma that we operated between 2005 and 2014. We performed an open pleurectomy and partial decortication of any visible lesion on the visceral pleura in all cases and both diaphragm and pericardium were always spared; Hyperthermic IntraTHOracic Chemotherapy was ran using Cisplatin 80 mg/m2 and Doxorubicin 25 mg/m2 at a target temperature of 42.5 °C for 60 min. RESULTS We operated on 26 patients (23 male and 3 female); epithelioid tumor was diagnosed in 23 cases. Twelve patients were in IMIG stage I and 14 in IMIG stage II; median overall survival for all patients, stage I and II were 35.6, 46 and 23 months respectively and disease free survival was 18, 18 and 16 months respectively. Our results for stage I were better than those reported in literature and were similar for stage II. We observe no 30- and 90- mortality and the rate of severe complication (all CTCAE stage 3) were 30%; the median postoperative stay was 7.5 days. CONCLUSIONS Our lung sparing approach for the treatment of pleural mesothelioma in early stages allows promising long term outcomes with a complete sparing of pulmonary and diaphragmatic function. Larger studies are needed to confirm our good results.
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Affiliation(s)
- P Bertoglio
- Division of Thoracic Surgery, Department of Surgical, Medical, Molecular, and Critical Area Pathology, University Hospital of Pisa, via Paradisa 2, 56100 Pisa, PI, Italy.
| | - M C Ambrogi
- Division of Thoracic Surgery, Department of Surgical, Medical, Molecular, and Critical Area Pathology, University Hospital of Pisa, via Paradisa 2, 56100 Pisa, PI, Italy
| | - A Chella
- Division of Pneumology, Cardio Thoracic and Vascular Department, University Hospital of Pisa, via Paradisa 2, 56100 Pisa, PI, Italy
| | - V Aprile
- Division of Thoracic Surgery, Department of Surgical, Medical, Molecular, and Critical Area Pathology, University Hospital of Pisa, via Paradisa 2, 56100 Pisa, PI, Italy
| | - P Dini
- Division of Thoracic Surgery, Cardio Thoracic and Vascular Department, University Hospital of Pisa, via Paradisa 2, 56100 Pisa, PI, Italy
| | - S Korasidis
- Division of Thoracic Surgery, Department of Surgical, Medical, Molecular, and Critical Area Pathology, University Hospital of Pisa, via Paradisa 2, 56100 Pisa, PI, Italy
| | - O Fanucchi
- Division of Thoracic Surgery, Cardio Thoracic and Vascular Department, University Hospital of Pisa, via Paradisa 2, 56100 Pisa, PI, Italy
| | - A Mussi
- Division of Thoracic Surgery, Department of Surgical, Medical, Molecular, and Critical Area Pathology, University Hospital of Pisa, via Paradisa 2, 56100 Pisa, PI, Italy
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Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation? Strahlenther Onkol 2017; 193:285-294. [DOI: 10.1007/s00066-017-1108-y] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2016] [Accepted: 01/27/2017] [Indexed: 12/16/2022]
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32
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Simone CB, Busch TM, Cengel KA. Radiotherapy and Photodynamic Therapy for Malignant Pleural Mesothelioma. ASBESTOS AND MESOTHELIOMA 2017. [DOI: 10.1007/978-3-319-53560-9_14] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Botticella A, Defraene G, Nackaerts K, Deroose CM, Coolen J, Nafteux P, Peeters S, Ricardi U, De Ruysscher D. Optimal gross tumor volume definition in lung-sparing intensity modulated radiotherapy for pleural mesothelioma: an in silico study. Acta Oncol 2016; 55:1450-1455. [PMID: 27732127 DOI: 10.1080/0284186x.2016.1234066] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
BACKGROUND The gross tumor volume (GTV) definition for malignant pleural mesothelioma (MPM) is ill-defined. We therefore investigated which imaging modality is optimal: computed tomography (CT) with intravenous contrast (IVC), positron emission tomography-CT (PET/CT) or magnetic resonance imaging (MRI). MATERIAL AND METHODS Sixteen consecutive patients with untreated stage I-IV MPM were included. Patients with prior pleurodesis were excluded. CT with IVC, 18FDG-PET/CT and MRI (T2 and contrast-enhanced T1) were obtained. CT was rigidly co-registered with PET/CT and with MRI. Three sets of pleural GTVs were defined: GTVCT, GTVCT+PET/CT and GTVCT+MRI. Quantitative and qualitative evaluations of the contoured GTVs were performed. RESULTS Compared to CT-based GTV definition, PET/CT identified additional tumor sites (defined as either separate nodules or greater extent of a known tumor) in 12/16 patients. Compared to either CT or PET/CT, MRI identified additional tumor sites in 15/16 patients (p = .7). The mean GTVCT, GTVCT+PET/CT and GTVCT+MRI [±standard deviation (SD)] were 630.1 cm3 (±302.81), 640.23 cm3 (±302.83) and 660.8 cm3 (±290.8), respectively. Differences in mean volumes were not significant. The mean Jaccard Index was significantly lower in MRI-based contours versus all the others. CONCLUSION As MRI identified additional pleural disease sites in the majority of patients, it may play a role in optimal target volume definition.
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Affiliation(s)
- Angela Botticella
- Department of Oncology, Experimental Radiation Oncology, KU Leuven–University of Leuven, Leuven, Belgium
| | - Gilles Defraene
- Department of Oncology, Experimental Radiation Oncology, KU Leuven–University of Leuven, Leuven, Belgium
| | - Kristiaan Nackaerts
- Respiratory Diseases/Respiratory Oncology Unit, KU Leuven–University of Leuven, University Hospitals Leuven, Leuven, Belgium
| | - Christophe M. Deroose
- Department Imaging and Pathology, Nuclear Medicine and Molecular Imaging, KU Leuven–University of Leuven, University Hospitals Leuven, Leuven, Belgium
| | - Johan Coolen
- Radiology Department, University Hospitals Leuven, Leuven, Belgium
| | - Philippe Nafteux
- Department of Thoracic Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Stephanie Peeters
- Department of Radiation Oncology, KU Leuven–University of Leuven, University Hospitals Leuven, Leuven, Belgium
| | - Umberto Ricardi
- Department of Oncology, Radiation Oncology, University of Turin, Turin, Italy
| | - Dirk De Ruysscher
- Department of Radiation Oncology, KU Leuven–University of Leuven, University Hospitals Leuven, Leuven, Belgium
- GROW–School for Oncology and Developmental Biology, Department of Radiation Oncology (MAASTRO clinic), Maastricht University Medical Center, Maastricht, The Netherlands
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Infante M, Morenghi E, Bottoni E, Zucali P, Rahal D, Morlacchi A, Ascolese AM, De Rose F, Navarria P, Crepaldi A, Testori A, Voulaz E, Errico V, Perrino M, Scorsetti M, Chiti A, Santoro A, Alloisio M. Comorbidity, postoperative morbidity and survival in patients undergoing radical surgery for malignant pleural mesothelioma. Eur J Cardiothorac Surg 2016; 50:1077-1082. [PMID: 27330149 DOI: 10.1093/ejcts/ezw215] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2016] [Revised: 04/19/2016] [Accepted: 04/26/2016] [Indexed: 12/21/2022] Open
Abstract
OBJECTIVES We examined a series of malignant pleural mesothelioma (MPM) patients who underwent radical surgery to explore relationships among comorbidity, postoperative morbidity and survival. METHODS A retrospective analysis was carried out of all MPM patients operated on in a single centre from 2000 to 2015. The Charlson Comorbidity Index (CCI) was used to classify patients according to their underlying condition. Postoperative complications were scored according to WHO-derived criteria. Survival comparisons were performed by Cox analysis. RESULTS Ninety-one patients underwent extrapleural pneumonectomy (EPP), 47 underwent pleurectomy decortication (PD) and 25 underwent palliative pleurectomy. The mean CCI of PD patients was significantly higher compared with that of EPP patients (P= 0.044). The frequency of grade 3+ complications was similar between EPP and PD (27 vs 26%). However, EPP patients had a 6-fold higher frequency of pleural sepsis (24 vs 4%, P= 0.002) occurring up to 695 days postoperatively. Median overall survival was 19 months (95% CI 13-25) after EPP, 30 months (95% CI 20-35) after PD and 13 months (95% CI 5-32) after palliative pleurectomy. At multivariate analysis, CCI (P< 0.001), histology (P= 0.014) and pleural sepsis (P= 0.001), but not complete resection, were significantly associated with survival. There was a trend in favour of PD over palliative resection after adjusting for histology and CCI. CONCLUSIONS The CCI is an independent predictor of survival in MPM patients undergoing radical surgery. Owing to its significant frequency and adverse impact, pleural sepsis may contribute to a reduced life expectancy after EPP. Surgical treatment of MPM remains debatable.
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Affiliation(s)
- Maurizio Infante
- Department of Thoracic Surgery, University Hospital Borgo Trento, Verona, Italy
| | - Emanuela Morenghi
- Clinical Research Unit, Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Edoardo Bottoni
- Department of Thoracic Surgery, Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Paolo Zucali
- Oncology and Hematology, Humanitas Clinical and Research Center, Humanitas University, Rozzano (Milan), Italy
| | - Daoud Rahal
- Department of Pathology, Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Andrea Morlacchi
- Department of Thoracic Surgery, Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Anna Maria Ascolese
- Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Fiorenza De Rose
- Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Pierina Navarria
- Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Alessandro Crepaldi
- Department of Thoracic Surgery, Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Alberto Testori
- Department of Thoracic Surgery, Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Emanuele Voulaz
- Department of Thoracic Surgery, Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Valentina Errico
- Department of Thoracic Surgery, Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Matteo Perrino
- Oncology and Hematology, Humanitas Clinical and Research Center, Humanitas University, Rozzano (Milan), Italy
| | - Marta Scorsetti
- Department of Radiotherapy and Radiosurgery, Humanitas Research Hospital, Rozzano (Milan), Italy
| | - Arturo Chiti
- Nuclear Medicine, Humanitas Clinical and Research Center, Humanitas University, Rozzano (Milan), Italy
| | - Armando Santoro
- Oncology and Hematology, Humanitas Clinical and Research Center, Humanitas University, Rozzano (Milan), Italy
| | - Marco Alloisio
- Department of Thoracic Surgery, Humanitas Research Hospital, Rozzano (Milan), Italy
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35
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Novello S, Pinto C, Torri V, Porcu L, Di Maio M, Tiseo M, Ceresoli G, Magnani C, Silvestri S, Veltri A, Papotti M, Rossi G, Ricardi U, Trodella L, Rea F, Facciolo F, Granieri A, Zagonel V, Scagliotti G. The Third Italian Consensus Conference for Malignant Pleural Mesothelioma: State of the art and recommendations. Crit Rev Oncol Hematol 2016; 104:9-20. [PMID: 27286698 DOI: 10.1016/j.critrevonc.2016.05.004] [Citation(s) in RCA: 55] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2015] [Revised: 03/17/2016] [Accepted: 05/10/2016] [Indexed: 11/26/2022] Open
Abstract
Malignant Pleural Mesothelioma (MPM) remains a relevant public health issue, and asbestos exposure is the most relevant risk factor. The incidence has considerably and constantly increased over the past two decades in the industrialized countries and is expected to peak in 2020-2025. In Italy, a standardized-rate incidence in 2011 among men was 3.5 and 1.25 per 100,000 in men and women, respectively, and wide differences are noted among different geographic areas. The disease remains challenging in terms of diagnosis, staging and treatment and an optimal strategy has not yet been clearly defined. The Third Italian Multidisciplinary Consensus Conference on Malignant Pleural Mesothelioma was held in Bari (Italy) in January 30-31, 2015. This Consensus has provided updated recommendations on the MPM management for health institutions, clinicians and patients.
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Affiliation(s)
- S Novello
- Department of Oncology, University of Turin, Italy.
| | - C Pinto
- Medical Oncology Unit, IRCCS-Arciospedale Santa Maria Nuova, Reggio Emilia, Italy
| | - V Torri
- Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
| | - L Porcu
- Department of Oncology, IRCCS-Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy
| | - M Di Maio
- Department of Oncology, University of Turin, Italy
| | - M Tiseo
- Division of Medical Oncology, Azienda Ospedaliera Universitaria di Parma, Italy
| | - G Ceresoli
- Thoracic Oncology Unit, Humanitas Gavazzeni, Bergamo, Italy
| | - C Magnani
- Cancer Epidemiology, University of Eastern Piedmont and CPO-Piemonte, Novara, Italy
| | - S Silvestri
- Istituto per lo Studio e la Prevenzione Oncologica, Florence, Italy
| | - A Veltri
- Department of Oncology, University of Turin, Italy
| | - M Papotti
- Department of Oncology, University of Turin, Italy
| | - G Rossi
- Ospedale Policlinico, Division of Human Pathology, Modena, Italy
| | - U Ricardi
- Department of Oncology, University of Turin, Italy
| | - L Trodella
- Department of Radiotherapy, Campus Bio-Medico University, Rome, Italy
| | - F Rea
- Azienda Ospedaliera, Division of Thoracic Surgery, Padua, Italy
| | - F Facciolo
- Regina Elena Cancer Institute, Division of Thoracic Surgery, Rome, Italy
| | - A Granieri
- University of Torino, Department of Psychology, Italy
| | - V Zagonel
- Veneto Oncology Institute, IRCCS Padova, Italy
| | - G Scagliotti
- Department of Oncology, University of Turin, Italy
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Thieke C, Nicolay NH, Sterzing F, Hoffmann H, Roeder F, Safi S, Debus J, Huber PE. Long-term results in malignant pleural mesothelioma treated with neoadjuvant chemotherapy, extrapleural pneumonectomy and intensity-modulated radiotherapy. Radiat Oncol 2015; 10:267. [PMID: 26715491 PMCID: PMC4696301 DOI: 10.1186/s13014-015-0575-5] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2015] [Accepted: 12/18/2015] [Indexed: 12/14/2022] Open
Abstract
Introduction We investigated the clinical outcome and the toxicity of trimodal therapy of malignant pleural mesothelioma (MPM) treated with neoadjuvant chemotherapy, extrapleural pneumonectomy (EPP) and adjuvant intensity-modulated radiotherapy (IMRT). Methods Chemotherapy regimens included Cisplatin/Pemetrexed, Carboplatin/Pemetrexed and Cisplatin/Gemcitabine, followed by EPP. 62 patients completed the adjuvant radiotherapy. IMRT was carried out in two techniques, either step&shoot or helical tomotherapy. Median target dose was 48 Gy to 54 Gy. Toxicity was scored with the Common Terminology Criteria (CTC) for Adverse Events. We used Kaplan-Meier method to estimate actuarial rate of locoregional control (LRC), distant control (DC) and overall survival (OS), measured from the date of surgery. Rates were compared using the logrank test. For multivariate analysis the Cox proportional hazard model was used. Results The median OS, LRC and DC times were 20.4, 31.4 and 21.4 months. The 1-, 2-, 3-year OS rates were 63, 42, 28 %, the LRC rates were 81, 60, 40 %, and the DC rates were 62, 48, 41 %. We observed no CTC grade 4 or grade 5 toxicity. Step&shoot and helical tomotherapy were equivalent both in dosimetric characteristics and clinical outcome. Biphasic tumor histology was associated with worse clinical outcome compared to epitheloid histology. Conclusions Mature clinical results of trimodal treatment for MPM were presented. They indicate that hemithoracic radiotherapy after EPP can be safely administered by either step&shoot IMRT and tomotherapy. However, the optimal prospective patient selection for this aggressive trimodal therapy approach remains unclear. This study can serve as a benchmark for current and future therapy concepts for MPM. Electronic supplementary material The online version of this article (doi:10.1186/s13014-015-0575-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Christian Thieke
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany. .,CCU Radiation Oncology, German Cancer Research Center, Heidelberg, Germany. .,Present address: Department of Radiation Oncology, University of Munich (LMU), Marchioninistr. 15, 81377, Munich, Germany.
| | - Nils H Nicolay
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.,CCU Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.,CCU Molecular Radiation Oncology, German Cancer Research Center, Heidelberg, Germany
| | - Florian Sterzing
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.,CCU Radiation Oncology, German Cancer Research Center, Heidelberg, Germany
| | - Hans Hoffmann
- Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany
| | - Falk Roeder
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.,CCU Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.,CCU Molecular Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.,Present address: Department of Radiation Oncology, University of Munich (LMU), Marchioninistr. 15, 81377, Munich, Germany
| | - Seyer Safi
- Department of Thoracic Surgery, Thoraxklinik, Heidelberg University Hospital, Heidelberg, Germany
| | - Juergen Debus
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany.,CCU Radiation Oncology, German Cancer Research Center, Heidelberg, Germany
| | - Peter E Huber
- Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg, Germany. .,CCU Radiation Oncology, German Cancer Research Center, Heidelberg, Germany. .,CCU Molecular Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
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de Perrot M, Feld R, Leighl NB, Hope A, Waddell TK, Keshavjee S, Cho BCJ. Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 2015; 151:468-73. [PMID: 26614413 DOI: 10.1016/j.jtcvs.2015.09.129] [Citation(s) in RCA: 86] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Revised: 08/24/2015] [Accepted: 09/13/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVE To evaluate a new protocol of accelerated hemithoracic intensity-modulated radiation therapy (IMRT) followed by extrapleural pneumonectomy (EPP) for patients with resectable malignant pleural mesothelioma (MPM). METHODS A total of 25 Gy of radiation was delivered in 5 daily fractions over 1 week to the entire ipsilateral hemithorax with concomitant boost of 5 Gy to volumes at high risk based on computed tomography and positron emission tomography scan findings. EPP was performed at 6 ± 2 days after the end of radiation therapy. Adjuvant chemotherapy was offered to patients with ypN2 disease. RESULTS A total of 62 patients were included between November 2008 and October 2014. One patient died in the hospital 2 months after EPP, for an operative mortality of 1.6%, and 2 died after discharged from the hospital for an overall treatment-related mortality (grade 5 toxicity) of 4.8%. Twenty-four patients (39%) developed grade 3 to 5 (grade 3+) complications. On final pathology, 94% of the patients were stage III or IV, and 52% had ypN2 disease. The median survival for all patients as an intention-to-treat analysis was 36 months. The median overall survival and disease-free survival was 51 and 47 months, respectively, in epithelial subtypes, compared with 10 and 8 months in biphasic subtypes (P = .001). Ipsilateral chest recurrence occurred in 8 patients. CONCLUSIONS Accelerated hemithoracic IMRT followed by EPP has become our preferred approach for resectable MPM. The results have been encouraging in patients with epithelial subtype.
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Affiliation(s)
- Marc de Perrot
- Division of Thoracic Surgery, Princess Margaret Cancer Centre and Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
| | - Ronald Feld
- Division of Medical Oncology, Princess Margaret Cancer Centre and Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Natasha B Leighl
- Division of Medical Oncology, Princess Margaret Cancer Centre and Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Andrew Hope
- Department of Radiation Oncology, Princess Margaret Cancer Centre and Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Thomas K Waddell
- Division of Thoracic Surgery, Princess Margaret Cancer Centre and Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - Shaf Keshavjee
- Division of Thoracic Surgery, Princess Margaret Cancer Centre and Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
| | - B C John Cho
- Department of Radiation Oncology, Princess Margaret Cancer Centre and Toronto General Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada
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Kishan AU, Cameron RB, Wang PC, Alexander S, Qi SX, Low DA, Kupelian PA, Steinberg ML, Lee JM, Selch MT, Lee P. Tomotherapy improves local control and changes failure patterns in locally advanced malignant pleural mesothelioma. Pract Radiat Oncol 2015; 5:366-73. [PMID: 26432677 DOI: 10.1016/j.prro.2015.07.010] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2015] [Revised: 07/17/2015] [Accepted: 07/30/2015] [Indexed: 12/31/2022]
Abstract
PURPOSE The purpose of the study was to determine whether intensity modulated radiation therapy delivered via helical tomotherapy improves local control (LC) after pleurectomy/decortication (P/D) for malignant pleural mesothelioma compared with 3-dimensional conformal radiation therapy (3D-CRT). METHODS AND MATERIALS Forty-five consecutive patients were treated with adjuvant radiation to 45 Gy in 1.8 Gy fractions after P/D between 2006 and 2014; 23 received 3D-CRT, and 22 received tomotherapy. Kaplan-Meier analysis was used to calculate overall survival, time to in-field or local failure (LF), and time to out-of-field failure. The Student t test and Fisher exact test were used to detect between-group differences. RESULTS Median follow-up time was 19.4 months and 12.7 months for the 3D-CRT and tomotherapy groups, respectively. Eighty-two percent of patients had T3/T4 disease, and 64% had positive nodes; 17.4% and 41% of patients in the 3D-CRT and tomotherapy groups had nonepithelioid histology, respectively. Mean planning target volume dose, percentage of planning target volume receiving 100% of the prescription dose, and lung doses were significantly greater with tomotherapy (P < .05), but toxicity rates (including radiation pneumonitis rates) were equivalent. LC was significantly improved with tomotherapy on Kaplan-Meier analysis with outcomes censored at 2 years (P < .05); uncensored, this became a trend (P = .06). Median time to LF was 19 months with tomotherapy and 10.9 months in 3D-CRT (the latter interval being less than the median follow-up in the tomotherapy group). On univariate analysis, treatment modality was the only significant predictor of LC (P < .05). Isolated LF was significantly more frequent with 3D-CRT (P < .05). Conversely, isolated out-of-field failure was significantly more frequent with tomotherapy (P < .05). Overall survival and out-of-field control were not significantly different. CONCLUSION Tomotherapy after P/D for malignant pleural mesothelioma is associated with improved target coverage that translates into improved LC compared with 3D-CRT. This is related to a change in failure patterns, with isolated LF being more common in the 3D-CRT group and isolated out-of-field failures predominating in the tomotherapy group.
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Affiliation(s)
- Amar U Kishan
- Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Robert B Cameron
- Division of Thoracic Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Pin-Chieh Wang
- Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Sherri Alexander
- Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Sharon X Qi
- Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Daniel A Low
- Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Patrick A Kupelian
- Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Michael L Steinberg
- Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Jay M Lee
- Division of Thoracic Surgery, Department of Surgery, David Geffen School of Medicine at UCLA, Los Angeles, California
| | - Michael T Selch
- Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California
| | - Percy Lee
- Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California.
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Early experience with intensity modulated proton therapy for lung-intact mesothelioma: A case series. Pract Radiat Oncol 2015; 5:e345-53. [PMID: 25572666 DOI: 10.1016/j.prro.2014.11.005] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2014] [Revised: 10/28/2014] [Accepted: 11/17/2014] [Indexed: 02/03/2023]
Abstract
PURPOSE The purpose of this study was to describe our experience implementing intensity modulated proton therapy (IMPT) for lung-intact malignant pleural mesothelioma (MPM), including patient selection, treatment planning, dose verification, and process optimization. METHODS AND MATERIALS Seven patients with epithelioid MPM were reviewed; 6 underwent pleurectomy, whereas 1 had biopsy alone. Four patients received IMPT and 3 received intensity modulated radiation therapy. Treatment plans for the other modality were created for dosimetric comparisons. Quality assurance processes included dose verification and robustness analysis. Image-guided setup was performed with the first isocenter, and couch shifts were applied to reposition to the second isocenter. RESULTS Treatment with IMPT was well tolerated and completed without breaks. IMPT plans were designed with 2 isocenters, 4 beams, and ≤64 energy layers per beam. Dose verification processes were completed in 3 hours. Total daily treatment time was approximately 45 minutes (20 minutes for setup and 25 minutes for delivery). IMPT produced lower mean doses to the contralateral lung, heart, esophagus, liver, and ipsilateral kidney, with increased contralateral lung sparing when mediastinal boost was required for nodal disease. CONCLUSIONS Our initial experience showed that IMPT was feasible for routine care of patients with lung-intact MPM.
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