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J Thorac Cardiovasc Surg 1999;117:54-65
© 1999 Mosby, Inc.


GENERAL THORACIC SURGERY

RESECTION MARGINS, EXTRAPLEURAL NODAL STATUS, AND CELL TYPE DETERMINE POSTOPERATIVE LONG-TERM SURVIVAL IN TRIMODALITY THERAPY OF MALIGNANT PLEURAL MESOTHELIOMA: RESULTS IN 183 PATIENTS

David J. Sugarbaker, MD, Raja M. Flores, MD, Michael T. Jaklitsch, MD, William G. Richards, PhD, Gary M. Strauss, MD, Joseph M. Corson, MD, Malcolm M. DeCamp, Jr, MD, Scott J. Swanson, MD, Raphael Bueno, MD, Jeanne M. Lukanich, MD, Elizabeth Healey Baldini, MD, MPH, Steven J. Mentzer, MD

From the Division of Thoracic Surgery and the Department of Pathology, Brigham and Women's Hospital; Surgical Services and the Department of Adult Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Mass; and Hematology-Oncology, University of Massachusetts, Worcester, Mass.

Read at the Seventy-eighth Annual Meeting of The American Association for Thoracic Surgery, Boston, Mass, May 3-6, 1998.

Received for publication May 8, 1998. Revisions requested June 30, 1998. Revisions received Sept 25, 1998. Accepted for publication Sept 29, 1998. Address for reprints: David J. Sugarbaker, MD, Division of Thoracic Surgery, Brigham and Women's Hospital, Boston, MA 02115.

Objectives: Our aim was to identify prognostic variables for long-term postoperative survival in trimodality management of malignant pleural mesothelioma.
Methods: From 1980 to 1997, 183 patients underwent extrapleural pneumonectomy followed by adjuvant chemotherapy and radiotherapy.
Results: Forty-three women and 140 men (age range 31-76 years) had a median follow-up of 13 months. The perioperative mortality rate was 3.8% (7 deaths) and the morbidity, 50%. Survival in the 176 remaining patients was 38% at 2 years and 15% at 5 years (median 19 months). Univariate analysis identified 3 prognostic variables associated with improved survival: epithelial cell type (52% 2-year survival, 21% 5-year survival, 26-month median survival; P = .0001), negative resection margins (44% at 2 years, 25% at 5 years, median 23 months; P = .02), and extrapleural nodes without metastases (42% at 2 years, 17% at 5 years, median 21 months; P = .004). Using the Cox proportional hazards, the relative risk of death was calculated for nonepithelial cell type (OR 3.0, CI 2.0-4.5; P < .0001), positive resection margins (OR 1.7, CI 1.2-2.6; P = .0082), and metastatic extrapleural nodes (OR 2.0, CI 1.3-3.2; P = .0026). Thirty-one patients with 3 positive variables had the best survival (68% 2-year survival, 46% 5-year survival, median 51 months; P = .013). A previously published staging system using these variables stratified survival (P < .05).
Conclusions: (1) Multimodality therapy including extrapleural pneumonectomy is feasible in selected patients with malignant pleural mesotheliomas, (2) pre-resectional evaluation of extrapleural nodes may select patients for radical therapy, (3) microscopic resection margins affect long-term survival, highlighting the need for further investigation of locoregional control, and (4) patients with epithelial, margin-negative, extrapleural node–negative resection had extended survival.




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J. Thorac. Cardiovasc. Surg.Home page
P. A. Rascoe, X. Cao, J. C. Daniel, S. D. Miller, and W. R. Smythe
Receptor tyrosine kinase and phosphoinositide-3 kinase signaling in malignant mesothelioma
J. Thorac. Cardiovasc. Surg., August 1, 2005; 130(2): 393 - 400.
[Abstract] [Full Text] [PDF]


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Jpn J Clin OncolHome page
R. Maruyama, F. Shoji, T. Okamoto, T. Miyamoto, T. Miyake, T. Nakamura, J. Ikeda, Y. Aoki, H. Wataya, H. Asoh, et al.
Triplet Chemotherapy with Cisplatin, Gemcitabine and Vinorelbine for Malignant Pleural Mesothelioma
Jpn. J. Clin. Oncol., August 1, 2005; 35(8): 433 - 438.
[Abstract] [Full Text] [PDF]


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MMCTSHome page
L. M. Argote-Greene, M. Y. Chang, and D. J. Sugarbaker
Extrapleural pneumonectomy for malignant pleural mesothelioma
MMCTS, June 28, 2005; 2005(0628): 133.
[Abstract] [Full Text] [PDF]


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Clin. Cancer Res.Home page
G. J. Gordon, G. N. Rockwell, P. A. Godfrey, R. V. Jensen, J. N. Glickman, B. Y. Yeap, W. G. Richards, D. J. Sugarbaker, and R. Bueno
Validation of Genomics-Based Prognostic Tests in Malignant Pleural Mesothelioma
Clin. Cancer Res., June 15, 2005; 11(12): 4406 - 4414.
[Abstract] [Full Text] [PDF]


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J. Thorac. Cardiovasc. Surg.Home page
J. J. Erasmus, M. T. Truong, W. R. Smythe, R. F. Munden, E. M. Marom, D. C. Rice, A. A. Vaporciyan, G. L. Walsh, B. S. Sabloff, L. D. Broemeling, et al.
Integrated computed tomography-positron emission tomography in patients with potentially resectable malignant pleural mesothelioma: Staging implications
J. Thorac. Cardiovasc. Surg., June 1, 2005; 129(6): 1364 - 1370.
[Abstract] [Full Text] [PDF]


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NEJMHome page
S. Neragi-Miandoab, S. P. Gangadharan, and D. J. Sugarbaker
Cardiac Sarcoma 14 Years after Treatment for Pleural Mesothelioma
N. Engl. J. Med., May 5, 2005; 352(18): 1929 - 1930.
[Full Text] [PDF]


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Clin. Cancer Res.Home page
M. Hazarika, R. M. White Jr., B. P. Booth, Y.-C. Wang, D. Y. Lee Ham, C. Y. Liang, A. Rahman, J. V.S. Gobburu, N. Li, R. Sridhara, et al.
Pemetrexed in Malignant Pleural Mesothelioma
Clin. Cancer Res., February 1, 2005; 11(3): 982 - 992.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
R. Bueno, J. Reblando, J. Glickman, M. T. Jaklitsch, J. M. Lukanich, and D. J. Sugarbaker
Pleural Biopsy: A Reliable Method for Determining the Diagnosis But Not Subtype in Mesothelioma
Ann. Thorac. Surg., November 1, 2004; 78(5): 1774 - 1776.
[Abstract] [Full Text] [PDF]


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JCOHome page
Y. Aelony
Need for Further Information on Pemetrexed Study
J. Clin. Oncol., October 15, 2004; 22(20): 4234 - 4235.
[Full Text] [PDF]


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ChestHome page
M. Pistolesi and J. Rusthoven
Malignant Pleural Mesothelioma: Update, Current Management, and Newer Therapeutic Strategies
Chest, October 1, 2004; 126(4): 1318 - 1329.
[Abstract] [Full Text] [PDF]


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JCOHome page
W. Weder, P. Kestenholz, C. Taverna, S. Bodis, D. Lardinois, M. Jerman, and R. A. Stahel
Neoadjuvant Chemotherapy Followed by Extrapleural Pneumonectomy in Malignant Pleural Mesothelioma
J. Clin. Oncol., September 1, 2004; 22(17): 3451 - 3457.
[Abstract] [Full Text] [PDF]


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Ann OncolHome page
E. Andreopoulou, P. J. Ross, M. E. R. O'Brien, H. E. R. Ford, K. Priest, T. Eisen, A. Norton, S. Ashley, and I. E. Smith
The palliative benefits of MVP (mitomycin C, vinblastine and cisplatin) chemotherapy in patients with malignant mesothelioma
Ann. Onc., September 1, 2004; 15(9): 1406 - 1412.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
D. J. Stewart, A. Martin-Ucar, J. E. Pilling, J. G. Edwards, K. J. O'Byrne, and D. A. Waller
The effect of extent of local resection on patterns of disease progression in malignant pleural mesothelioma
Ann. Thorac. Surg., July 1, 2004; 78(1): 245 - 252.
[Abstract] [Full Text] [PDF]


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J. Thorac. Cardiovasc. Surg.Home page
D. J. Sugarbaker, M. T. Jaklitsch, R. Bueno, W. Richards, J. Lukanich, S. J. Mentzer, Y. Colson, P. Linden, M. Chang, L. Capalbo, et al.
Prevention, early detection, and management of complications after 328 consecutive extrapleural pneumonectomies
J. Thorac. Cardiovasc. Surg., July 1, 2004; 128(1): 138 - 146.
[Abstract] [Full Text] [PDF]


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JNMHome page
H. Kramer, R. M. Pieterman, D.-J. Slebos, W. Timens, W. Vaalburg, G. H. Koeter, and H. J.M. Groen
PET for the Evaluation of Pleural Thickening Observed on CT
J. Nucl. Med., June 1, 2004; 45(6): 995 - 998.
[Abstract] [Full Text] [PDF]


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Molecular Cancer TherapeuticsHome page
M. K. Ozvaran, X. X. Cao, S. D. Miller, B. A. Monia, W. K. Hong, and W. R. Smythe
Antisense oligonucleotides directed at the bcl-xl gene product augment chemotherapy response in mesothelioma
Mol. Cancer Ther., May 1, 2004; 3(5): 545 - 550.
[Abstract] [Full Text] [PDF]


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ThoraxHome page
A Baldi, D Santini, F Vasaturo, M Santini, G Vicidomini, M P. Di Marino, V Esposito, A M Groeger, G Liuzzi, B Vincenzi, et al.
Prognostic significance of cyclooxygenase-2 (COX-2) and expression of cell cycle inhibitors p21 and p27 in human pleural malignant mesothelioma
Thorax, May 1, 2004; 59(5): 428 - 433.
[Abstract] [Full Text] [PDF]


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Eur. J. Cardiothorac. Surg.Home page
J.E. Pilling, D.J. Stewart, A.E. Martin-Ucar, S. Muller, K.J. O'Byrne, and D.A. Waller
The case for routine cervical mediastinoscopy prior to radical surgery for malignant pleural mesothelioma
Eur. J. Cardiothorac. Surg., April 1, 2004; 25(4): 497 - 501.
[Abstract] [Full Text] [PDF]


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RadioGraphicsHome page
A. Sharma, P. Fidias, L. A. Hayman, S. L. Loomis, K. H. Taber, and S. L. Aquino
Patterns of Lymphadenopathy in Thoracic Malignancies
RadioGraphics, March 1, 2004; 24(2): 419 - 434.
[Abstract] [Full Text] [PDF]


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RadioGraphicsHome page
Z. J. Wang, G. P. Reddy, M. B. Gotway, C. B. Higgins, D. M. Jablons, M. Ramaswamy, R. A. Hawkins, and W. R. Webb
Malignant Pleural Mesothelioma: Evaluation with CT, MR Imaging, and PET
RadioGraphics, January 1, 2004; 24(1): 105 - 119.
[Abstract] [Full Text] [PDF]


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ThoraxHome page
V H Gerbaudo, S Britz-Cunningham, D J Sugarbaker, and S T Treves
Metabolic significance of the pattern, intensity and kinetics of 18F-FDG uptake in malignant pleural mesothelioma
Thorax, December 1, 2003; 58(12): 1077 - 1082.
[Abstract] [Full Text] [PDF]


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ChestHome page
J. G. Edwards, D. E. B. Swinson, J. L. Jones, S. Muller, D. A. Waller, and K. J. O'Byrne
Tumor Necrosis Correlates With Angiogenesis and Is a Predictor of Poor Prognosis in Malignant Mesothelioma
Chest, November 1, 2003; 124(5): 1916 - 1923.
[Abstract] [Full Text] [PDF]


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ThoraxHome page
C Parker and E Neville
Lung cancer * 8: Management of malignant mesothelioma
Thorax, September 1, 2003; 58(9): 809 - 813.
[Full Text] [PDF]


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JCOHome page
V. W. Rusch
Pemetrexed and Cisplatin for Malignant Pleural Mesothelioma: A New Standard of Care?
J. Clin. Oncol., July 15, 2003; 21(14): 2629 - 2630.
[Full Text] [PDF]


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J. Thorac. Cardiovasc. Surg.Home page
R. M. Flores, T. Akhurst, M. Gonen, S. M. Larson, and V. W. Rusch
Positron emission tomography defines metastatic disease but not locoregional disease in patients with malignant pleural mesothelioma
J. Thorac. Cardiovasc. Surg., July 1, 2003; 126(1): 11 - 15.
[Abstract] [Full Text] [PDF]


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Ann. Thorac. Surg.Home page
J. H. Schouwink, L. Schultze Kool, E. J. Rutgers, F. A. N. Zoetmulder, N. van Zandwijk, M. J. v.d. Vijver, and P. Baas
The value of chest computer tomography and cervical mediastinoscopy in the preoperative assessment of patients with malignant pleural mesothelioma
Ann. Thorac. Surg., June 1, 2003; 75(6): 1715 - 1718.
[Abstract] [Full Text] [PDF]


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JNCI J Natl Cancer InstHome page
G. J. Gordon, R. V. Jensen, L.-L. Hsiao, S. R. Gullans, J. E. Blumenstock, W. G. Richards, M. T. Jaklitsch, D. J. Sugarbaker, and R. Bueno
Using Gene Expression Ratios to Predict Outcome Among Patients With Mesothelioma
J Natl Cancer Inst, April 16, 2003; 95(8): 598 - 605.
[Abstract] [Full Text] [PDF]


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ICVTSHome page
P. G. Phillips, G. Asimakopoulos, and M. O. Maiwand
Malignant pleural mesothelioma: outcome of limited surgical management
Interactive CardioVascular and Thoracic Surgery, March 1, 2003; 2(1): 30 - 34.
[Abstract] [Full Text] [PDF]


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J. Thorac. Cardiovasc. Surg.Home page
Y. Aelony
Missing data from mesothelioma study
J. Thorac. Cardiovasc. Surg., February 1, 2003; 125(2): 442 - 443.
[Full Text] [PDF]


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J. Thorac. Cardiovasc. Surg.Home page
H. I. Pass
Pleural mesothelioma in 2002: Going somewhere very slowly
J. Thorac. Cardiovasc. Surg., December 1, 2002; 124(6): 1074 - 1077.
[Full Text]


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J. Thorac. Cardiovasc. Surg.Home page
T. T. Lee, D. L. Everett, H.-K. G. Shu, T. M. Jahan, M. Roach III, J. L. Speight, R. B. Cameron, T. L. Phillips, A. Chan, and D. M. Jablons
Radical pleurectomy/decortication and intraoperative radiotherapy followed by conformal radiation with or without chemotherapy for malignant pleural mesothelioma
J. Thorac. Cardiovasc. Surg., December 1, 2002; 124(6): 1183 - 1189.
[Abstract] [Full Text]


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ChestHome page
P. Bonnette, G. B. Heckly, S. Villette, A. Fragola, J. H. Schouwink, and P. Bass
Intraoperative Photodynamic Therapy After Pleuropneumonectomy for Malignant Pleural Mesothelioma
Chest, November 1, 2002; 122(5): 1866 - 1867.
[Full Text] [PDF]


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Cancer Res.Home page
P. A. Janne, M. L. Taffaro, R. Salgia, and B. E. Johnson
Inhibition of Epidermal Growth Factor Receptor Signaling in Malignant Pleural Mesothelioma
Cancer Res., September 15, 2002; 62(18): 5242 - 5247.
[Abstract] [Full Text] [PDF]


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JNMHome page
V. H. Gerbaudo, D. J. Sugarbaker, S. Britz-Cunningham, M. F. Di Carli, C. Mauceri, and S. T. Treves
Assessment of Malignant Pleural Mesothelioma with 18F-FDG Dual-Head Gamma-Camera Coincidence Imaging: Comparison with Histopathology
J. Nucl. Med., September 1, 2002; 43(9): 1144 - 1149.
[Abstract] [Full Text] [PDF]


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J. Thorac. Cardiovasc. Surg.Home page
W. R. Smythe, I. Mohuiddin, M. Ozveran, and X. X. Cao
Antisense therapy for malignant mesothelioma with oligonucleotides targeting the bcl-xl gene product
J. Thorac. Cardiovasc. Surg., June 1, 2002; 123(6): 1191 - 1198.
[Abstract] [Full Text] [PDF]


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CarcinogenesisHome page
G. J. Gordon, K. Appasani, J. P. Parcells, N. K. Mukhopadhyay, M. T. Jaklitsch, W. G. Richards, D. J. Sugarbaker, and R. Bueno
Inhibitor of apoptosis protein-1 promotes tumor cell survival in mesothelioma
Carcinogenesis, June 1, 2002; 23(6): 1017 - 1024.
[Abstract] [Full Text] [PDF]


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Clin. Cancer Res.Home page
J. G. Edwards, S. P. Faux, S. M. Plummer, K. R. Abrams, R. A. Walker, D. A. Waller, and K. J. O'Byrne
Cyclooxygenase-2 Expression Is a Novel Prognostic Factor in Malignant Mesothelioma
Clin. Cancer Res., June 1, 2002; 8(6): 1857 - 1862.
[Abstract] [Full Text] [PDF]


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Am. J. Respir. Cell Mol. Bio.Home page
X. X. Cao, I. Mohuiddin, F. Ece, D. J. McConkey, and W. R. Smythe
Histone Deacetylase Inhibitor Downregulation of bcl-xl Gene Expression Leads to Apoptotic Cell Death in Mesothelioma
Am. J. Respir. Cell Mol. Biol., November 1, 2001; 25(5): 562 - 568.
[Abstract] [Full Text] [PDF]




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