S from connective tissue and account for approximately

Reoperative Pulmonary Resection in Patients With Metastatic Soft Tissue Sarcoma Helen W. Pogrebniak, MD, Jack A. Roth, MD, Seth M. Steinberg, PhD, Steven A. Rosenberg, MD, PhD, and Harvey I. Pass, MD Thoracic Oncology Section, Surgery Branch, and Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland Resection of pulmonary metastases from soft tissue sarcoma has been shown to be associated with a 3-year survival of 25% to 30%. The role of multiple resections for recurrent pulmonary metastases, however, has not been clearly defined. Since 1976, 43 patients have had two or more thoracic explorations for the purpose of resecting pulmonary metastases from adult soft tissue sarcoma at our institution. In 89 reexplorations, through either median sternotomy or lateral thoracotomy, the operative mortality was 0%, and 31 of the 43 patients (72%) could be rendered free of disease at the second thoracotomy. Median survival from the second thoracot- omy for the patients with resectable disease was 25 months, whereas median survival of patients who had unresectable disease was 10 months. A disease-free interval between the first and second thoracotomies of greater than 18 months was associated with prolonged survival from the second thoracotomy. Owing to lack of other therapies with proven salvage efficacy and in the absence of randomized trials, repeated thoracotomies to render patients free of disease from pulmonary softtissue sarcoma metastases appear justified considering the potential survival benefit and low attendant risk. (Ann Thoruc Surg 1991 ;52:197-203) oft tissue sarcomas are malignant tumors that arise S from connective tissue and account for approximately 1% of all malignancies. Sixty to 70% of soft tissue sarcomas occur in the extremities with the remainder at other sites such as the trunk, retroperitoneum, head and neck, and breast [l, 21. Aggressive surgical resection of the primary tumor combined with postoperative adjuvant therapy has resulted in 5-year survival rates of 40% to 60% For editorial comment, see page 178. for high-grade soft tissue sarcomas [l]. The lungs are the most common site of distant metastases, with recurrence usually within the first 24 months after management of the primary lesion [Z]. Several series, including our own [3], have documented long-term survival for patients who have had removal of their sarcoma pulmonary metastases, with 3- to 5-year survivals of 25%. Most thoracic surgeons at the present time favor an attempt to render patients with pulmonary metastatic soft tissue sarcoma surgically disease free, especially in the absence of more effective therapy, if the patient s primary site is under control, there are no other extrathoracic sites of disease, and the patient can withstand lung resection. Most series, however, do not concentrate on the unfortunate patients who subsequently have recurrence after initial pulmonary resection. The risk of multiple thoracotomies in these Presented at the Thirty-seventh Annual Meeting of the Southern Thoracic Surgical Association, Dorado, Puerto Rico, Nov %lo, 1990. Address reprint requests to Dr Pass, Thoracic Oncology Section, Surgery Branch, National Cancer Institute, National Institutes of Health, Building 10, Room 2807, Bethesda, MD 20892. patients and the possible long-term benefits, as well as the predictors of survival, have not been addressed in patients undergoing multiple metastasectomies in such a uniform group of patients. An initial report from our institution in 29 patients was suggestive of a survival benefit, yet long-term follow-up was limited [4]. The purpose of this report is to update this experience of multiple pulmonary metastasectomies with considerably longer follow-up time for all patients with soft tissue sarcomas under protocols of the Surgery Branch of the National Cancer Institute. The study includes 43 patients operated on between January 1976 and July 1990. Patients and Methods Patient Population From 1976 to 1990, 165 patients have had resection of presumed pulmonary metastases from high-grade soft tissue sarcomas by the Thoracic Oncology Section of the National Cancer Institute. The primary soft tissue sarcoma in these patients had been resected between 1974 and 1990. Of these 165 patients, 43 patients underwent two or more thoracic explorations for the purpose of removing metastases and are the subject of this review. Follow-up data are available on all 43 patients, with a median potential follow-up time of 81 months from the second operation. Ages ranged from 18 to 63 years with a median age of 41 years. There were 28 men and 15 women. Primary tumors were located in the extremity (n = 38), trunk (n = 2), head and neck (n = 2), or retroperitoneum (n = l), and all were high-grade (synovial sarcoma, 14; malignant fibrous histiocytoma, 9; leiomyosarcoma, 7; fibrosarcoma, 4; schwannoma, 3; neuroectodermal sar-

198 POGREBNIAK ET AL 1991;52: 197-203 coma, coma, each). 2; and alveolar soft parts sarcoma, chondrosarliposarcoma, and undifferentiated sarcoma, 1 Preoperative Eva1 ua t ion All patients were initially screened for inclusion in randomized clinical protocols evaluating the role of radical surgical resection and adjuvant chemotherapyiradiation therapy in the treatment of soft tissue sarcomas. Patients with Ewing s sarcoma and juvenile rhabdomyosascoma were excluded from these protocols. After excision of the primary tumor, patients were evaluated with thoracic computed tomographic scanning or linear tomography or both every 3 months for 2 years, and with radionuclide bone scans yearly. Patients with newly developing abnormalities consistent with pulmonary metastases were offered resection of the metastases if the primary tumor was controlled, extrapulmonary metastases were absent, and the amount of lung tissue remaining would provide the patients with sufficient pulmonary parenchymal reserve. In general, physiological staging (pulmonary function testing, cardiology evaluation) was not performed unless the patient had symptoms referable to the heart or lungs, the patient had undergone a formal pulmonary resection (ie, lobectomy) or had more then ten wedge resections at a previous thoracotomy, or a formal pulmonary resection was contemplated. Operative Procedure Conduct of the operation was as previously described [3]. Briefly, the metastases were resected through a median sternotomy or lateral thoracotomy using double-lumen endotracheal anesthesia. The right and left sides were individually explored by bimanual palpation of the collapsed lung. The thoracic cavity, including the mediastinum, chest wall, and hilar nodes, was thoroughly examined. Palpable abnormalities that did not appear to be obvious granulomas or intrapulmonary lymph nodes were excised with automatic stapling devices. Patients with nodules not amenable to wedge or segmental resections had formal pulmonary resection if they could be rendered free of disease, if lymph node sampling did not reveal metastatic sarcoma, and if discontinuous pleural metastatic disease was not present. All patients were monitored by an indwelling arterial line and on-line arterial digital oximetry. The number of metastases was determined and recorded for each operation. Roentgenographic Monitoring A nodule was defined as a focus of increased density that was spherical, based on either the pleura or parenchyma, and unassociated with linear densities. Newly developing nodules were considered highly suggestive of sarcoma metastases and, as described earlier, served as an absolute indication for exploration [5]. Chest computed tomographic examinations were performed with a GE 8800 CT/C scanner (General Electric Company, Fairfield, CT) by scanning the entire thorax in transaxial slices at 10-mmthick intervals, and the images were displayed on a 256 by 256 matrix. Contiguous 1-cm linear tomograms were obtained in the coronal plane throughout the entire depth of the lungs. S fa t is t ical Analysis Survival durations were computed from the date of the second thoracotomy until the date of the last known follow-up or date of death. Probabilities of survival were computed actuarially by the Kaplan-Meier method [6]. The statistical significance of the difference between survival curves was determined by the Mantel-Haenszel technique [7]. Demographic and clinical factors were analyzed for their simultaneous effects on survival and included possibility of complete resection of metastases, sex, age, location of the primary tumor, histology, interval from the primary resection to the first thoracotomy, disease-free interval from the first thoracotomy to the second thoracotomy, the number of metastases resected at the first and second thoracotomies, and the number of nodules present on preoperative roentgenographic studies. These factors were analyzed by means of the Cox proportional hazards model [8]. All p values are twosided. Results From 1976 to 1990, these 43 patients had a total of 132 thoracic explorations for presumptive metastatic soft tissue sarcoma. Histologically proven metastases were found in 131 of the 132 cases. The lone exception was a patient undergoing a sixth exploration for a single metastatic nodule thought to be alveolar soft parts sarcoma, which proved to be a granuloma. Preoperative Roentgenographic Studies As in previously reported studies, surveillance by either linear tomography or computed tomography was only moderately accurate. This is attested to by the fact that 22 patients were found to have unresectable disease at the second or subsequent thoracotomy owing to disease outside the confines of the lung or to too many parenchymal metastases. Moreover, the total number of nodules detected before all the procedures at which patients were rendered free of disease was 282, yet 419 nodules were resected (33% underestimation of disease). Operative Findings The operative approach in these 43 patients is summarized in Table 1. There were no fixed guidelines with regard to the operative approach, either by sternotomy or by thoractomy; however, after four median sternotomies, subsequent resections were performed by lateral thoracotomy, especially if dense adhesions had been noted or if the nodule(s) were deep in the lung parenchyma or posteriorly placed. The majority of the resections involved wedge resections only (83%), with formal anatomical resections required in the remainder: wedge only (one or more), 106 patients; wedge and segmentectomy, 1; segmentectomy alone, 5; wedge and lobectomy, 3; lobectomy alone, 10; wedge and chest wall resection, 3; and pneumonectomy, 4.

1991;52:197-203 POGREBNIAK ET AL 199 Table 1. Operative Approach for Recurrent Pulmonary Sarcoma Metastases: 1976 to 1990 Incision Used Exploration No. of Median No. Patients Sternotomy Thoracotomy 1 43 32 2 43 20 3 23 10 4 11 4 5 7 0 6 5 0 11 23 13 7 7 5 Of the 89 reoperative thoracotomies, resection was able to be performed in 65 (74%). Twenty-four of the 43 patients explored were ultimately found at operation to have unresectable disease and had wedge biopsy documentation of recurrence; of these 24, 12 patients had unresectable disease at the second thoracotomy (from which survival is measured in the study). Operative Mortality and Morbidity There were no operative or perioperative deaths. In the total of 89 reoperative thoracotomies in the 43 patients, there were five complications (6%): wound infection, 2; empyema, 1; arrythmia, 1; and prolonged air leak, 1. Actuarial Survival After Resection The median survival for all 43 patients from the time of the second thoracotomy was 19.3 months (Fig 1). Patients who could be rendered free of disease at the second thoracotomy had significantly longer postthoracotomy survival times (median, 25 months) than those with unresectable disease at the second thoracotomy (median, 10 months; p = 0.0007 for the overall differences between the curves) (Fig 2). At the time of this report 21 of the 22 patients who at subsequent thoracotomy had unresectable disease have died of sarcoma, whereas of the 21 patients who were always able to be rendered free of disease at the second through the sixth thoracotomy, 7 are presently free of disease, 3 are alive with roentgenographically unresectable disease, and 11 have died of sarcomatosis. Univariate Analyses Univariate (Mantel-Haenszel) analyses in the 43 patients indicated that sex, location of the primary tumor, and age did not significantly affect survival, although there were very slight trends toward improved survival in male patients, patients with an age less than 50 years, and those with extremity tumors. Histology of the tumor was not associated with differences in survival, although there was a slight trend toward decreased survival with malignant fibrous histiocytoma. The initial disease-free interval between resection of the primary tumor and the first thoracotomy was not a predictor of survival from the time of a second metastasectomy, although there was a trend (p = 0.069) toward increased survival for patients with initial disease-free intervals greater than 2 years compared with those with intervals less than 2 years. Disease-free interval between the first and second thoracotomy (Fig 3), however, was a predictor of long-term survival with patients living longer after the second thoracotomy if the time between thoracotomies was greater than 18 months compared with intervals less than 18 months (p = 0.0197). Neither the number of nodules seen on roentgenographic studies before the initial or the second thoracotomy was significantly predictive of survival from the second thoracotomy. There was a trend, nevertheless, toward decreased survival if five or more nodules were seen on the studies before the second metastasectomy (p = 0.081). The absolute number of metastases resected in the 43 patients at first thoracotomy, or in the 31 patients who could be rendered free of disease at the second thoracot- Fig I. Survival for 43 patients with soft tissue sarcoma having two or more explorations for pulmonary metastases. Median survival for all patients was 19.3 months from the time of the second exploration. I- z Lu 0 a: W a 10- A 1 I

200 POGREBNIAK ET AL REQPERATION FOR PULMONARY METASTASES 1991;52197-203 Fig 2. Survival for patients having two or more thoracotomies for pulmonu y metastases from soft tissue sarcomas. Patients who could be rendered free of disease had significantly longer survival than patients found to have unresectabla disease (p = 0.0007). 0 Resectable at Second Thoracotomy o Unresectable at Second Thoracotqmy SURVIVAL POST SECOND THORACOTOMY (MONTHS) omy, was not a predictor of survival after the second thoracotomy. Statistical Modeling of Prognostic Factors The Cox proportional hazards modeling technique was used to identify factors that could be important in determining length of survival. Two models were developed to examine which of the following independent factors may be jointry predictive of survival: histology, number of metastases at first and second thoracotomy, number of nodules on the preoperative studies, interval between primary resection and first thoracotomy, disease-free interval between the first and second thoracotomy, site of the primary tumor, year of primary operation, year of first thoracotomy, sex, and age. In the first model, all 43 patients were considered, whereas in the second model the 12 patients who could not have complete resection at the second thoracotomy were excluded on the premise that these patients are different compared with successfully resected patients. Details of the parameters and their associated relative risks may be found in Table 2. The best model that included all 43 patients suggests that the most important factor in survival is whether or not a patient has had a successful second thoracotomy. Adjusting for the effect of the second thoracotomy outcome, having a disease-free interval of greater than 1.5 years is associated with a smaller risk of death than is a disease-free interval of less Fig 3. A disease-free interval of 2.5 years or less between the first and second thoracotomies was associated with a shorter survival time from the second thoracotomy than disease-free intervals of 1.5 years or more (p = 0.0297). 0 Disease-Free Interval 0-548 Days o Disease-Free Interval Greater Than 548 Days 0 i I SURVIVAL POST SECOND THORACOTOMY (MONTHS)

~ 1991;52: 197-203 POGREBNIAK ET AL 201 Table 2. Cox Proportional Hazards Modeling for Factors Predictive of Survival: All 43 Patients Parameter p 95% C1 for Variable Estimate Value RR RR Unresectable at second 1.09 0.0065 2.97 1.35, 6.51 thoracotomy Disease-free interval -1.20 0.037 0.30 0.10, 0.92 Age 0.60 0.031 1.82 1.05, 3.99 C1 = confidence interval; RR = relative risk than 1.5 years. Also increasing age from 10 to 29 years to 30 to 59 years, or from 30 to 59 years to more than 60 years, was associated with an increased risk of death. The model that examines only the patients who could be resected at the second thoracotomy is seen in Table 3. According to this model, adjusting for other factors, having between five and 15 nodules on the preoperative studies before the second thoracotomy is associated with a greater risk than having one to four nodules; being female is associated with a higher risk than being male; and increased age is associated with a greater risk of death. Comment We have previously reported two separate series of patients who have had resection of pulmonary soft tissue sarcoma metastases [3, 91. In both series, when the survival was measured from the time of the thoracotomy performed for the first pulmonary recurrence, there was a 24% to 28% 3-year actuarial survival for all patients and a 32% to 38% 3-year actuarial survival for patients who could be rendered disease free. These series alluded to a subset of patients who had recurrence after the initial thoracotomy with isolated pulmonary metastases. The present study comments on the ability to salvage these patients with repeated thoracotomies during the period 1974 to 1990. The reason for performing such an analysis is rather elemental in that if the survival of the patients after the second thoracotomy was relatively short (ie, 12 months), criticism of this aggressive approach could be valid. Moreover, if the risk of performing multiple thoracotomies was substantial, either in terms of morbidity with long hospital convalescence or prohibitive operative mortality, few thoracic surgeons would be expected to have much enthusiasm with regard to patient benefit. It is Table 3. Cox Proportional Hazards Modeling for 31 Patients Who Underwent Resection at the Second Thoracotorny Parameter p 95% C1 for Variable Estimate Value RR RR Nodules at second 1.60 0.032 4.95 1.16, 21.12 thoracotomy Sex (female) 1.55 0.016 4.71 1.34, 16.52 Age group 1.21 0.013 3.35 1.28, 8.76 C1 = confidence interval; RR = relative risk. very difficult in these types of studies to define such survival benefit with regard to morbidity of the associated operation. If one considers that the total number of hospital days necessary for the 132 resections was 1,049, and the total survival time was 52,601 days, then the ratio of time out of the hospital to time in the hospital for 2 to 5 reoperations was 50 to 1, ie, the patients in this series averaged about 1 week in the hospital for every year of survival. Moreover, this ratio of 50 to 1 was constant whether patients received 2, 3, 4, 5, or 6 operations to render them disease free. Certainly, this ratio, which can only be regarded as theoretically pragmatic, nevertheless suggests that the cost to the patient in this series with regard to therapy time is small compared with survival duration. Another more ambitious reason for examining this unique group of patients was to try to define prethoracotomy prognostic indicators that could predict which patients would benefit from multiple thoracotomies, as has been performed in the analyses of other metastasectomy series from our institution. The following caveats, of course, must be reiterated early in this discussion: (1) there must be some type of natural selection occurring even before the patients are considered for multiple thoracotomies, because patients must be in a better risk category to begin with to be able to be considered for such an approach, (2) these patients, for the most part, are young, with good physiological reserve, which enables them to be considered for such an approach, and (3) none of the results of such a series of homogeneous histologies should be extended as guidelines for the management of other cancers metastatic to the lung. There was no operative mortality for any of the 43 patients in this group who underwent 89 reoperative thoracotomies, the majority of patients were discharged within a week of the procedure, and the complication rate of 6% is probably acceptable. One would expect such mortality/morbidity results for this group of patients because the majority was in a functionally low risk category and had had minimal pulmonary parenchymal resection at the initial thoracotomy. The use of the median sternotomy for reoperative noncardiac thoracic operations should, in fact, have a lower associated morbidity than that seen in cardiac operations owing to the fact that the pericardium usually remains closed, and the technique for a redo sternotomy has been standardized, resulting in low complication rates. Nevertheless, as the number of explorations increased, we shifted to the use of lateral thoracotomy (>5 explorations), and fortunately, the preoperative studies in the majority of these situations revealed only unilateral disease. The degree of resected lung was dictated by the concept of lung conservation; hence, the inordinate number of wedge resections compared with segmentectomy, lobectomy, or pneumonectomy. Automatic stapling devices were used in all the procedures, and we did not encounter any malfunction leading to patient morbidity even after multiple stapling events. The importance of completely freeing the lung from the chest wall, diaphragm, and undersurface of the sternum cannot be overemphasized to more safely accom-

202 POGREBNIAK ET AL 1991;52:197-203 plish the wedge resection with an adequate but not excessive margin of normal surrounding lung tissue. With regard to the benefit of repeated thoracotomies for resection of metastatic sarcoma, there is no way in the absence of a randomized trial to have uniform agreement regarding its efficacy. Such a trial would entail randomizing patients to no therapy, best salvage chemotherapy, or attempted resection. All the patients in this series received, as per National Cancer Institute, Surgery Branch, high-grade sarcoma protocols, Adriamycin (doxorubicin hydrochloride; Adria Laboratories, Columbus, OH) and Cytoxan (cyclophosphamide; Bristol-Myers, Evansville, IN) after resection of the primary tumor. Because the patients had recurrence with pulmonary metastases, another salvage regimen would be in order; specifically, isophosphamide-etoposide with or without additional Adriamycin [lo]. It is to be noted, however, that the median survival for patients with progressive sarcoma not amenable to operative intervention is 12 months [ll]. One could argue, then, that patients who are able to have repeated metastasectomies, by definition, must be in a better prognostic category because they have not had recurrence elsewhere, which would make them ineligible for operative intervention. Nevertheless, it is to be noted that in the first series of multiple thoracotomies for sarcoma reported from our institution, there was a cohort of 6 patients who were not explored for recurrent pulmonary metastases on the basis of their roentgenographic findings. The median survival for this group was 7 months [4]. In this follow-up study, the most significant prognostic variable for survival after thoracotomy is the ability to render the patient free of disease at that operation. These data seem to be more objective in that attempted resection was performed in all 43 patients, yet the 12 who could not undergo resection had significantly decreased survival. The only other factor that, considered alone, had an impact on long-term survival was the disease-free interval between the first and the second thoracotomy. The beneficial interval of 1.5 years is significantly longer than the 6 months described in the first report. The discrepancy may be due to the addition of more patients as well as a longer follow-up time for all the patients in the series. Many patient characteristics, of themselves, including sex, age, location of tumor, and histology were not predictive of survival, nor were any parameters regarding the original tumor biology, ie, disease-free interval from the time of primary resection to first thoracotomy or the number of metastases resected at the first or second thoracotomy. As described in our total series of patients having one or more resections, the absolute number of metastases did not influence survival if the patients could be rendered free of disease. The inability of the number of nodules on preoperative studies to predict which patients would be long-term survivors is probably due to heterogeneity of the data, as it was necessary to combine the results of computed tomography and the less sensitive and less specific linear tomography, because some of the patients were not imaged by computed tomography early in the series when the second thoracotomy was performed. The Cox analysis confirms the univariate analysis for the full set of 43 patients that the prime factors influencing survival after a second metastasectomy were the diseasefree interval between the first and second thoracotomy and resectability. It is interesting that when only the successfully resected patients at the second thoracotomy are considered in the analysis, the number of nodules on preoperative studies before the second thoracotomy becomes a significant factor along with sex and age. It must be remembered, however, that these Cox models are based on a small number of patients and thus are very sensitive to each patient's survival experience. Also, because the patients in this study are those who required second thoracotomies, by necessity, the patients who lived long enough to have a second thoracotomy are selected. These patients were not randomized to any of the prognostic factors identified as being important, and they were treated in multiple protocols. Moreover, other important factors including supportive care could affect the outcome. Nevertheless, the patients in this series constitute a reasonably extensive series of patients who have in common two or more thoracotomies after the removal of a primary soft tissue sarcoma. Philosophically, considering the small number of cases of soft tissue sarcoma that occur each year, much of the data presented regarding aggressive resection of metastases could be regarded as anecdotal. Moreover, only institutions with an interest in such a disease would be able to amass an experience to negate the aforementioned anecdotal arguments. Currently, then, despite the limited number of cases and focused interest of select institutions, we recommend the use of multiple thoracotomies for patients who have recurrence after initial resection of pulmonary metastases from soft tissue sarcomas. One must recognize the inability of present roentgenographic techniques to visualize all metastatic foci in the lung, and therefore, one will probably encounter more disease than is expected. There are no real guidelines for the number of nodules that would be a "cut-off'' and contraindicate exploration for these patients. Therefore, at our institution we continue to explore patients with as many as six or seven computed tomographic abnormalities if there are no other factors to prevent thoracotomy. Finally, once the chest is open and thorough exploration has been performed, if it is believed that resection of all disease can be performed without affecting pulmonary reserve, all attempts should be made to render the patient disease free. Hopefully, new therapies in the future, either as an alternative or adjuvant to aggressive surgical resection, will increase the long-term survival. References 1. Rosenberg SA, Tepper J, Glatstein E, et al. Prospective randomized evaluation of adjuvant chemotherapy in adults with soft tissue sarcomas of the extremities. Cancer 1983;52: 424-34. 2. Potter DA, Glenn J, Kinsella T, et al. Patterns of recurrence in

1991;52:197-203 POGREBNIAK ET AL 203 patients with high grade soft-tissue sarcoma. J Clin Oncol 1985;3:353-66. 3. Jablons D, Steinberg SM, Roth J, Pittaluga S, Rosenberg SA, Pass HI. Metastasectomy for soft tissue sarcoma: further evidence for efficacy and prognostic indicators. J Thorac Cardiovasc Surg 1989;97:695705. 4. Rizzoni WE, Pass HI, Wesley MN, Rosenberg SA, Roth JA. Resection of recurrent pulmonary metastases in patients with soft-tissue sarcoma. Arch Surg 1986;121:1248-52. 5. Pass HI, Dwyer A, Makuch R, Roth JA. Detection of pulmonary metastases in patients with osteogenic and soft tissue sarcoma: the superiority of CT scan compared with conventional linear tomograms using dynamic analyses. J Clin Oncol 1985;3:1261-5. 6. Kaplan EL, Meier P. Non-parametric estimation from incomplete observation. J Am Stat Assoc 1958;53:457-81. 7. Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966;50:163-70. 8. Cox DR. Regression models and life-tables. J R Stat SOC B 1972;34:187-220. 9. Putnam JB, Roth JA, Wesley MN, et al. Analysis of prognostic factors in patients undergoing resection of pulmonary metastases from soft tissue sarcomas. J Thorac Cardiovasc Surg 1984;87:26&8. 10. Miser JS, Kinsella TJ, Triche TJ, et al. Ifosfamide and mesna uroprotection and etoposide: an effective regimen in the treatment of recurrent sarcomas and other tumors of children and young adults. J Clin Oncol 1987;5:1191-8. 11. Rosenberg SA, Suit HD, Baker LH. Sarcomas of the soft tissues. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer, principles and practice of oncology. 2nd ed. Philadelphia: J. B. Lippincott, 1985:124%91. DISCUSSION DR LEWIS WETSTEIN (Freehold, NJ): Dr Pogrebniak, these are, I believe, very important and interesting data. I question, however, the role of pneumonectomy in metastatic disease; regardless, I am here to learn. I have two questions. What is the role of pneumonectomy when patients have metastatic disease, and can you tell me how those 4 patients did subsequently? Maybe we should be performing pneumonectomy in all of them; I guess that is the best way to prevent any recurrence! DR POGREBNIAK: Our belief is that the minimal resection you can do with the most preservation of lung parenchyma is optimal. A few select patients required pneumonectomy to render them disease free, and we have shown that if you can render them disease free, they have approximately a 14-month greater survival. These patients are young, and physiologically they tolerated pneumonectomy very well. So, in that small handful of patients who can be rendered free of disease by pneumonectomy, we think it is indicated but should be very carefully selected. As far as trying to subselect them out, I cannot recall the data offhand as to whether or not they fared any differently. DR CLINTON E. BAISDEN (Keesler AFB, MS): I had the same question, and I was just going to try to hold you to it. What happened to the 4 patients who had pneumonectomy, specifically those 4? DR PASS: The patients who had pneumonectomies were very rare, namely, those patients who had central lesions. The 4 patients we did pneumonectomies on did not do well long term. DR BAISDEN: The reason I wanted to know is not to criticize, but because I think we are all stuck with this particular situation, where we are presented with a patient who has what appears to be a limited recurrence that we know it would take-or have very high suspicions it would take-a pneumonectomy to render this patient clinically disease free. I was hoping you would tell me there were 1 or 2 patients who got very good results from this, because we wrestle with this problem all the time. DR FREDERICK L. GROVER (San Antonio, TX): In the sarcoma patient, is there ever a place for debulking pulmonary metastasis for later adjuvant treatment? DR POGREBNIAK: Debulking in terms of not able to render them completely free of disease, no. Data from the prior series that looked at whether or not in a nonrandomized, noncontrolled fashion adjuvant chemotherapy was of any benefit proved it not to be. So we do not believe that you should debulk a patient to make him or her eligible for adjuvant therapy.