Abstract
Background
After lung-sparing radiotherapy for malignant pleural mesothelioma (MPM), local failure at sites of previous gross disease represents the dominant form of failure. Our aim is to investigate if selective irradiation of the gross pleural disease only can allow dose escalation.
Materials and methods
In all, 12 consecutive stage I–IV MPM patients (6 left-sided and 6 right-sided) were retrospectively identified and included. A magnetic resonance imaging-based pleural gross tumor volume (GTV) was contoured. Two sets of planning target volumes (PTV) were generated for each patient: (1) a “selective” PTV (S-PTV), originating from a 5-mm isotropic expansion from the GTV and (2) an “elective” PTV (E-PTV), originating from a 5-mm isotropic expansion from the whole ipsilateral pleural space. Two sets of volumetric modulated arc therapy (VMAT) treatment plans were generated: a “selective” pleural irradiation plan (SPI plan) and an “elective” pleural irradiation plan (EPI plan, planned with a simultaneous integrated boost technique [SIB]).
Results
In the SPI plans, the average median dose to the S‑PTV was 53.6 Gy (range 41–63.6 Gy). In 4 of 12 patients, it was possible to escalate the dose to the S‑PTV to >58 Gy. In the EPI plans, the average median doses to the E‑PTV and to the S‑PTV were 48.6 Gy (range 38.5–58.7) and 49 Gy (range 38.6–59.5 Gy), respectively. No significant dose escalation was achievable.
Conclusion
The omission of the elective irradiation of the whole ipsilateral pleural space allowed dose escalation from 49 Gy to more than 58 Gy in 4 of 12 chemonaive MPM patients. This strategy may form the basis for nonsurgical radical combined modality treatment of MPM.
Zusammenfassung
Hintergrund
Beim malignen Pleuramesotheliom (MPM) ist nach lungenschonender Radiotherapie das lokale Scheitern an Stellen eines früheren, sichtbaren Tumors die dominierende Form des Scheiterns. Unser Ziel ist es, zu untersuchen, ob die selektive Bestrahlung nur des sichtbaren Pleuratumors eine Dosiseskalation ermöglicht.
Material und Methoden
Es wurden 12 konsekutive MPM-Patienten in Phase I–IV (6 links- und 6 rechtshändig) retrospektiv identifiziert und inkludiert. Ein MRT-basiertes makroskopisches Tumorvolumen (GTV) der Pleura wurde umrandet. Für jeden Patienten wurden zwei Typen von Planungszielvolumen (PTV) erzeugt: (1) ein „selektives“ PTV (S-PTV), das einer isotropen Expansion von 5 mm vom GTV entstammt, und (2) ein „elektives“ PTV (E-PTV), das einer isotropen Expansion von 5 mm von der ganzen ipsilateralen Pleurahöhle entstammt. Zwei verschiedene Behandlungspläne mit volumetrisch modulierter Bogentherapie (VMAT) wurden erstellt: ein „selektiver“ pleuraler Bestrahlungsplan (SPI-Plan) und ein „elektiver“ pleuraler Bestrahlungsplan (EPI-Plan; geplant mit simultan integrierter Boost-Technik [SIB]).
Ergebnisse
In den SPI-Plänen betrug die durchschnittliche mittlere Dosis beim S‑PTV 53,6 Gy (Spanne 41–63,6 Gy). Bei 4 von 12 Patienten ließ sich die Dosis beim S‑PTV auf >58 Gy eskalieren. In den EPI-Plänen betrugen die durchschnittlichen mittleren Dosen beim E‑PTV und beim S‑PTV 48,6 Gy (Spanne 38,5–58,7 Gy) bzw. 49 Gy (Spanne 38,6–59,5 Gy). Eine signifikante Dosiseskalation war nicht möglich.
Schlussfolgerung
Das Weglassen der elektiven Bestrahlung der ganzen ipsilateralen Pleurahöhle ermöglichte bei 4 von 12 chemonaiven MPM-Patienten eine Dosiseskalation von 49 Gy bis über 58 Gy. Diese Strategie kann die Basis für eine nichtchirurgische, radikal kombinierte Modalitätsbehandlung von MPM bilden.
Similar content being viewed by others
References
Baas P, Fennell D, Kerr KM, Van Schil PE, Haas RL, Peters S, Guidelines Committee ESMO (2015) Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol 26(S5):v31–v39
Van Meerbeeck JP, Gaafar R, Manegold C, Van Klaveren RJ, Van Marck EA, Vincent M, European Organisation for Research and Treatment of Cancer Lung Cancer Group, National Cancer Institute et al (2005) Randomized phase III study of cisplatin with or without raltitrexed in patients with malignant pleural mesothelioma: An intergroup study of the European Organisation for Research and Treatment of Cancer Lung Cancer Group and the National Cancer Institute of Canada. J Clin Oncol 23:6881–6889
Vogelzang NJ, Rusthoven JJ, Symanowski J, Denham C, Kaukel E, Ruffie P et al (2003) Phase III study of pemetrexed in combination with cisplatin versus cisplatin alone in patients with malignant pleural mesothelioma. J Clin Oncol 21:2636–2644
Scherpereel A, Astoul P, Baas P, Berghmans T, Clayson H, de Vuyst P, European Respiratory Society, European Society of Thoracic Surgeons Task Force et al (2010) Guidelines of the European Respiratory Society and the European Society of Thoracic Surgeons for the management of malignant pleural mesothelioma. Eur Respir J 35:479–495
Cao C, Tian D, Park J, Allan J, Pataky KA, Yan TD et al (2014) A systematic review and meta-analysis of surgical treatments for malignant pleural mesothelioma. Lung Cancer 83:240–245
Bovolato P, Casadio C, Billè A, Ardissone F, Santambrogio L, Ratto GB et al (2014) Does surgery improve survival of patients with malignant pleural mesothelioma? A multicenter retrospective analysis of 1365 consecutive patients. J Thorac Oncol 9:390–396
Reynders K, Illidge T, Siva S, Chang JY, De Ruysscher D (2015) The abscopal effect of local radiotherapy: using immunotherapy to make a rare event clinically relevant. Cancer Treat Rev 41:503–510 (Jun)
Marcq E, Pauwels P, van Meerbeeck JP, Smits EL (2015) Targeting immune checkpoints: New opportunity for mesothelioma treatment? Cancer Treat Rev 41:914–924
Haas AR, Sterman DH (2013) Malignant pleural mesothelioma: Update on treatment options with a focus on novel therapies. Clin Chest Med 34:99–111
Minatel E, Trovo M, Polesel J, Rumeileh IA, Baresic T, Bearz A et al (2012) Tomotherapy after pleurectomy/decortication or biopsy for malignant pleural mesothelioma allows the delivery of high dose of radiation in patients with intact lung. J Thorac Oncol 7:1862–1866
Minatel E, Trovo M, Polesel J, Baresic T, Bearz A, Franchin G et al (2014) Radical pleurectomy/decortication followed by high dose of radiation therapy for malignant pleural mesothelioma. Final results with long-term follow-up. Lung Cancer 83:78–82
Rosenzweig KE, Zauderer MG, Laser B, Krug LM, Yorke E, Sima CS et al (2012) Pleural intensity-modulated radiotherapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 83:1278–1283
Fodor A, Fiorino C, Dell’Oca I, Broggi S, Pasetti M, Cattaneo GM et al (2011) PET-guided dose escalation tomotherapy in malignant pleural mesothelioma. Strahlenther Onkol 187:736–743
Feigen M, Lee ST, Lawford C, Churcher K, Zupan E, Scott AM et al (2011) Establishing locoregional control of malignant pleural mesothelioma using high-dose radiotherapy and (18) F‑FDG PET/CT scan correlation. J Med Imaging Radiat Oncol 55:320–332
Rimner A, Spratt DE, Zauderer MG, Rosenzweig KE, Wu AJ, Foster A et al (2014) Failure patterns after hemithoracic pleural intensity modulated radiation therapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 90:394–401
Chance WW, Rice DC, Allen PK, Tsao AS, Fontanilla HP, Liao Z et al (2015) Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma: toxicity, patterns of failure, and a matched survival analysis. Int J Radiat Oncol Biol Phys 91:149–156
Minatel E, Trovo M, Bearz A, Di Maso M, Baresic T, Drigo A et al (2015) Radical radiation therapy after lung-sparing surgery for malignant pleural Mesothelioma: Survival, pattern of failure, and prognostic factors. Int J Radiat Oncol Biol Phys 93:606–613
Rusch VW (1995) A proposed new international TNM staging system for malignant pleural mesothelioma. From the International Mesothelioma Interest Group. Chest 108:1122–1128
Botticella A, Defraene G, Nackaerts K, Deroose CM, Coolen J, Nafteux P, Peeters S, De Ruysscher D (2015) Optimization of gross tumor volume definition and treatment planning in lung-sparing volumetric modulated arc therapy for pleural mesothelioma. Ann Oncol 26(Supplement 1):i48–i50
Botticella A, Defraene G, Nackaerts K, Deroose CM, Coolen J, Nafteux P et al (2016) Optimal gross tumor volume definition in lung-sparing intensity modulated radiotherapy for pleural mesothelioma: An in silico study. Acta Oncol 55:1450–1455
Gagliardi G, Constine LS, Moiseenko V, Correa C, Pierce LJ, Allen AM et al (2010) Radiation dose-volume effects in the heart. Int J Radiat Oncol Biol Phys 76:77–85
Allen AM, Czerminska M, Jänne PA, Sugarbaker DJ, Bueno R, Harris JR et al (2006) Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma. Int J Radiat Oncol Biol Phys 65:640–645
Brock KK, Dawson LA (2014) Point: Principles of magnetic resonance imaging integration in a computed tomography-based radiotherapy workflow. Semin Radiat Oncol 24:169–174
Krayenbuehl J, Hartmann M, Lomax AJ, Kloeck S, Hug EB, Ciernik IF (2010) Proton therapy for malignant pleural mesothelioma after extrapleural pleuropneumonectomy. Int J Radiat Oncol Biol Phys 78:628–634
Acknowledgements
A. B. is supported by a grant from the Stichting tegen kanker/Fondation contre le cancer (CA/2014/354) and by Kom op Tegen Kanker (Stand up to Cancer, The Flemish Cancer Society).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
A. Botticella, G. Defraene, K. Nackaerts, C. Deroose, J. Coolen, P. Nafteux, B. Vanstraelen, S. Joosten, L.A.W. Michiels, S. Peeters, and D. DeRuysscher declare that they have no competing interests.
Ethical standards
This article does not contain any studies with human participants or animals performed by any of the authors.
Caption Electronic Supplementary Material
Rights and permissions
About this article
Cite this article
Botticella, A., Defraene, G., Nackaerts, K. et al. Does selective pleural irradiation of malignant pleural mesothelioma allow radiation dose escalation?. Strahlenther Onkol 193, 285–294 (2017). https://doi.org/10.1007/s00066-017-1108-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00066-017-1108-y
Keywords
- Malignant pleural mesothelioma
- Lung-sparing VMAT
- Nonsurgical treatments
- Selective pleural irradiation
- Elective pleural irradiation