Abstract
Objective
This study aims to report on patients (pts) with potentially resectable pleural mesothelioma treated with induction chemotherapy (CT) followed by extrapleural pneumonectomy (EPP) and adjuvant intensity-modulated radiation therapy (IMRT).
Methods
From 2002 to 2008 a retrospective review found 16 consecutive mesothelioma pts planned for trimodality care. CT involved a platinum-based doublet. EPP was carried out after pt restaging. IMRT to a dose of 54 Gy was given at least 4 weeks after EPP. Study endpoints included toxicity, dosimetric parameters, time to recurrence, and survival.
Results
Two pts progressed during CT and did not undergo EPP. One pt died after surgery. Thirteen pts (81 %) completed all treatments. Concerning IMRT, the mean of mean lung doses (MLDs) was 9.28 Gy. The mean percent of lung volume receiving 5 Gy (V5) and 20 Gy (V20) was 81.3 and 5.0 %, respectively. Acute radiation pulmonary toxicities included two grade 3 events. V30 was significantly associated with ≥grade 2 pulmonary toxicity (p = 0.041). There were no pulmonary-related deaths. Mean follow-up from CT start for 16 pts was 17.7 months (range, 1.3 to 66.3). Median survival (MS) was 20.2 months for pts completing therapy. Actuarial overall survival at 3 years was 31.6 %. Pathologic nodal stage did not correlate with overall or recurrence-free survival. Median time to local and/or distant recurrence from CT start was 15.3 months for pts completing therapy. All pts with local and regional failures also had distant failure. Two pts failed distantly only.
Conclusion
IMRT resulted in minimal pulmonary toxicity. Local control and survival remain challenging despite trimodality care.
Similar content being viewed by others
References
Butchart EG, Ashcroft T, Barnsley WC, Holden MP (1976) Pleuropneumonectomy in the management of diffuse malignant mesothelioma of the pleura. Experience with 29 patients. Thorax 31(1):15–24
Mujoomdar AA, Sugarbaker DJ (2008) Hyperthermic chemoperfusion for the treatment of malignant pleural mesothelioma. Semin Thorac Cardiovasc Surg 20(4):298–304
Rice DC, Stevens CW, Correa AM, Vaporciyan AA, Tsao A, Forster KM, Walsh GL, Swisher SG, Hofstetter WL, Mehran RJ, Roth JA, Liao Z, Smythe WR (2007) Outcomes after extrapleural pneumonectomy and intensity-modulated radiation therapy for malignant pleural mesothelioma. Ann Thorac Surg 84(5):1685–1692, discussion 1692-1683
Rice TW, Adelstein DJ, Kirby TJ, Saltarelli MG, Murthy SR, Van Kirk MA, Wiedemann HP, Weick JK (1994) Aggressive multimodality therapy for malignant pleural mesothelioma. Ann Thorac Surg 58(1):24–29
Richards WG, Zellos L, Bueno R, Jaklitsch MT, Janne PA, Chirieac LR, Yeap BY, Dekkers RJ, Hartigan PM, Capalbo L, Sugarbaker DJ (2006) Phase I to II study of pleurectomy/decortication and intraoperative intracavitary hyperthermic cisplatin lavage for mesothelioma. J Clin Oncol 24(10):1561–1567
Rusch VW, Rosenzweig K, Venkatraman E, Leon L, Raben A, Harrison L, Bains MS, Downey RJ, Ginsberg RJ (2001) A phase II trial of surgical resection and adjuvant high-dose hemithoracic radiation for malignant pleural mesothelioma. J Thorac Cardiovasc Surg 122(4):788–795
Sugarbaker DJ, Heher EC, Lee TH, Couper G, Mentzer S, Corson JM, Collins JJ Jr, Shemin R, Pugatch R, Weissman L et al (1991) Extrapleural pneumonectomy, chemotherapy, and radiotherapy in the treatment of diffuse malignant pleural mesothelioma. J Thorac Cardiovasc Surg 102(1):10–14, discussion 14-15
Sugarbaker DJ, Richards WG, Garcia JP (1997) Extrapleural pneumonectomy for malignant mesothelioma. Adv Surg 31:253–271
Yajnik S, Rosenzweig KE, Mychalczak B, Krug L, Flores R, Hong L, Rusch VW (2003) Hemithoracic radiation after extrapleural pneumonectomy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 56(5):1319–1326
Zellos LS, Sugarbaker DJ (2002) Multimodality treatment of diffuse malignant pleural mesothelioma. Semin Oncol 29(1):41–50
Gupta V, Mychalczak B, Krug L, Flores R, Bains M, Rusch VW, Rosenzweig KE (2005) Hemithoracic radiation therapy after pleurectomy/decortication for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 63(4):1045–1052
Pass HI, Kranda K, Temeck BK, Feuerstein I, Steinberg SM (1997) Surgically debulked malignant pleural mesothelioma: results and prognostic factors. Ann Surg Oncol 4(3):215–222
Sugarbaker DJ, Flores RM, Jaklitsch MT, Richards WG, Strauss GM, Corson JM, DeCamp MM Jr, Swanson SJ, Bueno R, Lukanich JM, Baldini EH, Mentzer SJ (1999) Resection margins, extrapleural nodal status, and cell type determine postoperative long-term survival in trimodality therapy of malignant pleural mesothelioma: results in 183 patients. J Thorac Cardiovasc Surg 117(1):54–63, discussion 63-55
Allen AM, Den R, Wong JS, Zurakowski D, Soto R, Janne PA, Zellos L, Bueno R, Sugarbaker DJ, Baldini EH (2007) Influence of radiotherapy technique and dose on patterns of failure for mesothelioma patients after extrapleural pneumonectomy. Int J Radiat Oncol Biol Phys 68(5):1366–1374
Flores RM, Zakowski M, Venkatraman E, Krug L, Rosenzweig K, Dycoco J, Lee C, Yeoh C, Bains M, Rusch V (2007) Prognostic factors in the treatment of malignant pleural mesothelioma at a large tertiary referral center. J Thorac Oncol 2(10):957–965
Sugarbaker DJ, Jaklitsch MT, Bueno R, Richards W, Lukanich J, Mentzer SJ, Colson Y, Linden P, Chang M, Capalbo L, Oldread E, Neragi-Miandoab S, Swanson SJ, Zellos LS (2004) Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies. J Thorac Cardiovasc Surg 128(1):138–146
Allen AM, Czerminska M, Janne PA, Sugarbaker DJ, Bueno R, Harris JR, Court L, Baldini EH (2006) Fatal pneumonitis associated with intensity-modulated radiation therapy for mesothelioma. Int J Radiat Oncol Biol Phys 65(3):640–645
Miles EF, Larrier NA, Kelsey CR, Hubbs JL, Ma J, Yoo S, Marks LB (2008) Intensity-modulated radiotherapy for resected mesothelioma: the Duke experience. Int J Radiat Oncol Biol Phys 71(4):1143–1150
Rice DC, Smythe WR, Liao Z, Guerrero T, Chang JY, McAleer MF, Jeter MD, Correa A, Vaporciyan AA, Liu HH, Komaki R, Forster KM, Stevens CW (2007) Dose-dependent pulmonary toxicity after postoperative intensity-modulated radiotherapy for malignant pleural mesothelioma. Int J Radiat Oncol Biol Phys 69(2):350–357
van Sandick JW, Kappers I, Baas P, Haas RL, Klomp HM (2008) Surgical treatment in the management of malignant pleural mesothelioma: a single institution’s experience. Ann Surg Oncol 15(6):1757–1764
Sugarbaker DJ (2006) Macroscopic complete resection: the goal of primary surgery in multimodality therapy for pleural mesothelioma. J Thorac Oncol 1(2):175–176
Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, Shank B, Solin LJ, Wesson M (1991) Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 21(1):109–122
Ahamad A, Stevens CW, Smythe WR, Liao Z, Vaporciyan AA, Rice D, Walsh G, Guerrero T, Chang J, Bell B, Komaki R, Forster KM (2003) Promising early local control of malignant pleural mesothelioma following postoperative intensity modulated radiotherapy (IMRT) to the chest. Cancer J (Sudbury, Mass) 9(6):476–484
Ramella S, Trodella L, Mineo TC, Pompeo E, Stimato G, Gaudino D, Valentini V, Cellini F, Ciresa M, Fiore M, Piermattei A, Russo P, Cesario A, D’Angelillo RM (2010) Adding ipsilateral V20 and V30 to conventional dosimetric constraints predicts radiation pneumonitis in stage IIIA-B NSCLC treated with combined-modality therapy. Int J Radiat Oncol Biol Phys 76(1):110–115. doi:10.1016/j.ijrobp.2009.01.036
Conflict of interest
Dr. Adelstein has obtained grant funding for research purposes from the following companies: AstraZeneca, Sonafi-Aventis, Inc., and GlaxoSmithKline. On behalf of all other authors, the corresponding author reports that there is no conflict of interest to disclose.
Ethical standards
IRB approval was obtained for this retrospective review. All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008.
Author information
Authors and Affiliations
Corresponding author
Additional information
This work was presented in part at the 2009 ASTRO meeting.
Rights and permissions
About this article
Cite this article
Murphy, E.S., Adelstein, D.J., Murthy, S.C. et al. Impact of intensity-modulated radiation therapy on outcomes for malignant pleural mesothelioma treated with trimodality therapy. J Radiat Oncol 3, 159–166 (2014). https://doi.org/10.1007/s13566-014-0142-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s13566-014-0142-y