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Ann Thorac Surg 2001;72:1149-1154
© 2001 The Society of Thoracic Surgeons
a Thoracic Service, Department of Surgery, New York, New York, USA
b Thoracic Oncology Service, Department of Medicine, New York, New York, USA
c Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, New York, USA
Address reprint requests to Dr Rusch, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021
e-mail: ruschv{at}mskcc.org
Presented at the Poster Session of the Thirty-seventh Annual Meeting of The Society of Thoracic Surgeons, New Orleans, LA, Jan 29–31, 2001.
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Abstract |
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Methods. All patients undergoing thoracotomy after induction chemotherapy from 1993 through 1999 were reviewed. Univariate and multivariate methods for logistic regression model were used to identify predictors of adverse events.
Results. Induction chemotherapy included mitomycin, vinblastine, and cisplatin (179 patients), carboplatin and paclitaxel (152 patients), and other combinations (139 patients). Eighty-five patients (18%) received preoperative radiation. Operations were pneumonectomy (97 patients), lobectomy (297 patients), lesser resection (18 patients), and exploration only (58 patients). Total mortality was 7 of 297 (2.4%) and 11 of 97 (11.3%) for all lobectomies and pneumonectomies, respectively, but mortality was 11 of 46 (23.9%) for right pneumonectomy. Complications developed in 179 patients (38%). By multiple regression analysis, right pneumonectomy (p = 0.02), blood loss (p = 0.01), and forced expiratory volume in one second (percent predicted) (p = 0.01) predicted complications. No factor emerged to explain this high right pneumonectomy mortality rate.
Conclusions. Pulmonary resection after neoadjuvant therapy is associated with acceptable overall morbidity and mortality. However, right pneumonectomy is associated with a significantly increased risk and should be performed only in selected patients.
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Patients and methods |
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Morbidity and mortality data were also retrieved from the charts. All complications occurring during the hospitalization were recorded and categorized as minor or major. Pneumonia, respiratory failure requiring intubation for greater than 48 hours, adult respiratory distress syndrome, bronchial stump leak, empyema, reoperation for bleeding, myocardial infarction, heart failure, arrhythmia requiring treatment, renal failure requiring dialysis, cerebrovascular accident, sepsis, or pulmonary embolism were considered major complications. Mortality was recorded as in-hospital mortality when it occurred during the same hospitalization as the operation, or as late mortality when it was related to the operation but occurred after the initial hospital discharge.
Statistical methods
Potential factors contributing to morbidity were examined first in univariate analyses. Most of the variables were tested by Pearson’s or Kendall’s Tau’s correlation coefficients to determine whether the potential risk factors were truly independent predictors. Then a multivariate logistic regression analysis was performed. Because of the small number of deaths, univariate and multivariate analyses were not undertaken to predict mortality. Fisher’s exact test was used to assign the significance of the association between the type of resection and mortality. Statistical analyses were completed using SPSS 10.0 statistical software (Statistical Product and Service Solutions; SPSS Inc, Chicago, IL).
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Surgical resection information
Information about the operations performed is shown in Table 2. The most common operation was a lobectomy (63.2%). Pneumonectomies were performed on 20.6% of patients, and explorations only on 12.3% of patients. Extended resections, defined as resections of the chest wall, pericardium, major vessels, vertebral bodies, or diaphragm, were performed on 102 patients (21.7%). In general, patients undergoing all forms of pulmonary resection were carefully managed by perioperative fluid restriction. No routine monitoring by Swan-Ganz or central venous catheter was used, and intensive hemodynamic measurements were not generally available for analysis. An R0, complete resection, was achieved in 78.1% of patients; an R1 was achieved in 7.9% of patients; an R2 was achieved in 1.7% of patients; and no resection was done in 12.3% of patients. Twenty-two patients (4.7%) received intraoperative brachytherapy. Adenocarcinoma was the predominant tumor histology that occurred in 263 patients (56.0%), whereas squamous cell carcinoma was seen in 124 patients (26.4%), large cell carcinoma in 53 patients (11.3%), and NSCLC, not otherwise specified, in 30 patients (6.4%).
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The forced expiratory volume in one second (FEV1) (percent predicted) for the right pneumonectomy patients who died was not statistically different than the FEV1 (percent predicted) for those who survived (0.738 and 0.781, respectively; p = 0.537). Seven of the 21 right pneumonectomy patients (33.3%) who received MVP as induction treatment died; 4 of the 25 patients (16%) who received other types of chemotherapy died (p = 0.2981; Fisher’s exact test). Ten of the 11 right pneumonectomy patients did not receive induction radiation, and the radiation status is unknown for 1 patient.
Morbidity
Complications developed in 179 patients (38.1%). Table 4 shows the morbidity by procedure. The most common complications are shown in Table 5. Respiratory was the most common complication, and the second most common was cardiac arrhythmia.
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Comment |
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Although our study is limited by its retrospection, it has allowed us to analyze the outcome of a very large number of patients treated in a relatively uniform manner. Radiation and chemotherapy were frequently administered at outside institutions but operations and postoperative follow-up were carried out at our institution, in a homogeneous manner within a single surgical group. Our overall surgical mortality of 3.8% compares favorably with previous studies reports in which patients were not given any induction therapy. Our results are also similar with those reported by Deslauriers and colleagues [12], in which 25% of the patients were in trials involving neoadjuvant or adjuvant therapy.
With respect to morbidity, postoperative complication rates in the range of 30% are reported both in studies in which patients did not receive induction therapy and in studies in which they did [11–13]. The most common complications are cardiorespiratory. Our total morbidity was 38.1%, but our major complication rate is 26.6%, which is very similar to that of previous studies. Therefore the impact of induction therapy on the overall morbidity rate does not seem to be significant.
Right pneumonectomy is known to be associated with a higher morbidity and mortality. In 1989, the M.D. Anderson Cancer Center reported an operative mortality rate of 12% for right pneumonectomy as compared with 1% for left pneumonectomy [14]. Also before the era of induction therapy, the Brigham and Women’s Hospital reported that right-sided resections were associated with an increased risk of major complications, especially dysrhythmias [15]. In the previously cited Southwest Oncology Group study [11], 6 of the 8 postoperative deaths followed pneumonectomies, but the side of resections was not reported. Thus our 23.9% mortality rate for right pneumonectomy exceeds that usually reported in patients not receiving induction therapy, but there is little previous information regarding this issue after combined modality therapy. One notable point is that almost half of the deaths after right pneumonectomy in our study occurred after initial discharge from the hospital. We performed statistical analyses to characterize patients with right pneumonectomy who died or developed complications as compared with those who did not. No demographic, clinical, functional, or surgical variables thus far explain the high operative risk of this patient subset.
Our analyses showed that the FEV1 (percent predicted) significantly predicts morbidity. As seen in Table 6, the DLCO (percent predicted) approaches significance as a predictor by univariate analysis. Further analyses showed that the FEV1 (percent predicted) is very linearly correlated with the DLCO (percent predicted) (coefficient = 0.445; p less than 0.001), which explains why only the FEV1 (percent predicted) is a significant predictor factor in the multivariate model. Within the confines of this retrospective study, it has not been possible to define an absolute cutoff point for the FEV1 (percent predicted) in which most complications became unavoidable. Analyses have been performed using the values of FEV1 (percent predicted) as a continuous variable. In clinical practice, the postoperative predicted FEV1 and DLCO (ppoFEV1 and ppoDLCO) derived from a quantitative ventilation-perfusion scan and the preoperative pulmonary function tests are considered potential predictors of complications [16]. Unfortunately, the combined results of a ventilation-perfusion scan and of complete pulmonary function tests could only be retrieved for 63 patients in this retrospective study. Only 17 of these patients developed complications. Therefore, the role of ppoFEV1 and ppoDLCO in predicting morbidity and mortality could not be assessed in our study. This should be investigated in future prospective studies. Other factors previously suggested as important by some authors [17, 18], including the amount of perioperative fluid administration and surgical techniques, should be assessed in future studies. These factors cannot be accurately evaluated in a retrospective study.
In summary, pulmonary resection after induction chemotherapy or chemoradiation can generally be performed with acceptable morbidity and mortality. Our data suggest that patients should be carefully selected for operation especially with respect to their pulmonary function, and that intraoperative blood loss should be minimized. In our experience, right pneumonectomy is associated with a significantly increased risk of postoperative morbidity and mortality, and therefore, should be performed very selectively only when no alternative resection is possible. The precise role of bronchial or vascular sleeve resection, or both, after induction therapy, advocated by some authors as an alternative to pneumonectomy [19], has not been fully defined yet. The etiology of respiratory failure, which is the main cause of mortality after right pneumonectomy, remains unclear from our analyses and warrants further investigation in prospective studies.
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S. Fujita, N. Katakami, Y. Takahashi, K. Hirokawa, A. Ikeda, C. Tabata, T. Mio, and M. Mishima Postoperative complications after induction chemoradiotherapy in patients with non-small-cell lung cancer Eur J Cardiothorac Surg, June 1, 2006; 29(6): 896 - 901. [Full Text] [PDF]
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M. Dancewicz, J. Kowalewski, and J. Peplinski Factors associated with perioperative complications after pneumonectomy for primary carcinoma of the lung Interact CardioVasc Thorac Surg, April 1, 2006; 5(2): 97 - 100. [Abstract] [Full Text] [PDF]
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M. de Perrot, E. Fadel, O. Mercier, S. Mussot, A. Chapelier, and P. Dartevelle Long-term results after carinal resection for carcinoma: Does the benefit warrant the risk? J. Thorac. Cardiovasc. Surg., January 1, 2006; 131(1): 81 - 89. [Abstract] [Full Text] [PDF]
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L. W. Martin, A. M. Correa, W. Hofstetter, W. K. Hong, R. Komaki, J. B. Putnam Jr, D. C. Rice, W. R. Smythe, S. G. Swisher, A. A. Vaporciyan, et al. The evolution of treatment outcomes for resected stage IIIA non-small cell lung cancer over 16 years at a single institution J. Thorac. Cardiovasc. Surg., December 1, 2005; 130(6): 1601 - 1610. [Abstract] [Full Text] [PDF]
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F. Barlesi, C. Doddoli, J.-P. Torre, R. Giudicelli, P. Fuentes, P. Thomas, and P. Astoul Comparative prognostic features of stage IIIAN2 and IIIB non-small-cell lung cancer patients treated with surgery after induction therapy Eur J Cardiothorac Surg, October 1, 2005; 28(4): 629 - 634. [Abstract] [Full Text] [PDF]
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P. Van Schil, J. Van Meerbeeck, G. Kramer, T. Splinter, C. Legrand, G. Giaccone, C. Manegold, and N. van Zandwijk Morbidity and mortality in the surgery arm of EORTC 08941 trial Eur. Respir. J., August 1, 2005; 26(2): 192 - 197. [Abstract] [Full Text] [PDF]
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W. R. Burfeind Jr, T. A. D'Amico, E. M. Toloza, W. G. Wolfe, and D. H. Harpole Low Morbidity and Mortality for Bronchoplastic Procedures With and Without Induction Therapy Ann. Thorac. Surg., August 1, 2005; 80(2): 418 - 422. [Abstract] [Full Text] [PDF]
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E. Perrot, B. Guibert, P. Mulsant, S. Blandin, I. Arnaud, P. Roy, L. Geriniere, and P.-J. Souquet Preoperative Chemotherapy Does Not Increase Complications After Nonsmall Cell Lung Cancer Resection Ann. Thorac. Surg., August 1, 2005; 80(2): 423 - 427. [Abstract] [Full Text] [PDF]
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C. Doddoli, F. Barlesi, D. Trousse, S. Robitail, S. Yena, P. Astoul, R. Giudicelli, P. Fuentes, and P. Thomas One hundred consecutive pneumonectomies after induction therapy for non-small cell lung cancer: An uncertain balance between risks and benefits J. Thorac. Cardiovasc. Surg., August 1, 2005; 130(2): 416 - 425. [Abstract] [Full Text] [PDF]
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E. Pezzetta, R. Stupp, A. Zouhair, L. Guillou, P. Taffe, C. von Briel, T. Krueger, and H.-B. Ris Comparison of neoadjuvant cisplatin-based chemotherapy versus radiochemotherapy followed by resection for stage III (N2) NSCLC Eur J Cardiothorac Surg, June 1, 2005; 27(6): 1092 - 1098. [Abstract] [Full Text] [PDF]
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J. L. Port, R. J. Korst, P. C. Lee, M. A. Levin, D. E. Becker, R. Keresztes, and N. K. Altorki Surgical Resection for Residual N2 Disease After Induction Chemotherapy Ann. Thorac. Surg., May 1, 2005; 79(5): 1686 - 1690. [Abstract] [Full Text] [PDF]
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D. J. Stewart, A. E. Martin-Ucar, J. G. Edwards, K. West, and D. A. Waller Extra-pleural pneumonectomy for malignant pleural mesothelioma: the risks of induction chemotherapy, right-sided procedures and prolonged operations Eur J Cardiothorac Surg, March 1, 2005; 27(3): 373 - 378. [Abstract] [Full Text] [PDF]
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G. E. Darling, A. Abdurahman, Q.-L. Yi, M. Johnston, T. K. Waddell, A. Pierre, S. Keshavjee, and R. Ginsberg Risk of a Right Pneumonectomy: Role of Bronchopleural Fistula Ann. Thorac. Surg., February 1, 2005; 79(2): 433 - 437. [Abstract] [Full Text] [PDF]
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R. S. Andrade, K. A. Kesler, J. L. Wilson, J. A. Brooks, B. D. Reichwage, K. M. Rieger, L. H. Einhorn, and J. W. Brown Short- and Long-Term Outcomes after Large Pulmonary Resection for Germ Cell Tumors After Bleomycin-Combination Chemotherapy Ann. Thorac. Surg., October 1, 2004; 78(4): 1224 - 1228. [Abstract] [Full Text] [PDF]
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R. M. D'Angelillo, L. Trodella, and S. Ramella Assessing the value of neoadjuvant chemoradiotherapy and pathologic downstaging in the treatment of non-small cell lung cancer. J. Thorac. Cardiovasc. Surg., September 1, 2004; 128(3): 489 - 490. [Full Text] [PDF]
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L. Trodella, P. Granone, S. Valente, S. Margaritora, G. Macis, A. Cesario, R. M. D'Angelillo, V. Valentini, G. M. Corbo, V. Porziella, et al. Neoadjuvant concurrent radiochemotherapy in locally advanced (IIIA-IIIB) non-small-cell lung cancer: long-term results according to downstaging Ann. Onc., March 1, 2004; 15(3): 389 - 398. [Abstract] [Full Text] [PDF]
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F. Leo, P. Solli, L. Spaggiari, G. Veronesi, F. de Braud, M. E. Leon, and U. Pastorino Respiratory function changes after chemotherapy: an additional risk for postoperative respiratory complications? Ann. Thorac. Surg., January 1, 2004; 77(1): 260 - 265. [Abstract] [Full Text] [PDF]
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G. Veronesi, M. E. Leon, and L. Spaggiari Safety of bronchoplastic resection after induction therapy for lung cancer J. Thorac. Cardiovasc. Surg., November 1, 2003; 126(5): 1670 - 1671. [Full Text] [PDF]
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D. C. Betticher, S.-F. Hsu Schmitz, M. Totsch, E. Hansen, C. Joss, C. von Briel, R. A. Schmid, M. Pless, J. Habicht, A. D. Roth, et al. Mediastinal Lymph Node Clearance After Docetaxel-Cisplatin Neoadjuvant Chemotherapy Is Prognostic of Survival in Patients With Stage IIIA pN2 Non-Small-Cell Lung Cancer: A Multicenter Phase II Trial J. Clin. Oncol., May 1, 2003; 21(9): 1752 - 1759. [Abstract] [Full Text] [PDF]
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P. A. Fuentes Pneumonectomy: historical perspective and prospective insight Eur J Cardiothorac Surg, April 1, 2003; 23(4): 439 - 445. [Full Text] [PDF]
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D. L. Miller, C. Deschamps, G. D. Jenkins, A. Bernard, M. S. Allen, and P. C. Pairolero Completion pneumonectomy: factors affecting operative mortality and cardiopulmonary morbidity Ann. Thorac. Surg., September 1, 2002; 74(3): 876 - 884. [Abstract] [Full Text] [PDF]
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J. Martin, R. J. Ginsberg, E. S. Venkatraman, M. S. Bains, R. J. Downey, R. J. Korst, M. G. Kris, and V. W. Rusch Long-Term Results of Combined-Modality Therapy in Resectable Non-Small-Cell Lung Cancer J. Clin. Oncol., April 15, 2002; 20(8): 1989 - 1995. [Abstract] [Full Text] [PDF]
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A. A. Vaporciyan, K. W. Merriman, F. Ece, J. A. Roth, W. R. Smythe, S. G. Swisher, G. L. Walsh, J. C. Nesbitt, and J. B. Putnam Jr Incidence of major pulmonary morbidity after pneumonectomy: association with timing of smoking cessation Ann. Thorac. Surg., February 1, 2002; 73(2): 420 - 426. [Abstract] [Full Text] [PDF]
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