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Survival after surgical resection for high-grade chest wall sarcomas
Survival After Surgical Resection for High-Grade Chest Wall Sarcomas Roger R. Perry, MD, David Venzon, PhD, Jack A. Roth, MD, and Harvey I. Pass, MD Surgery Branch and Biostatistics and Data Management Section, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
Indications for chest wall resection of metastatic or locally recurrent sarcoma and for subsequent bony reconstruction are controversial. Twenty-eight patients had chest wall resection for high-grade primary, metastatic, or recurrent sarcoma. In all patients, resection with selective reconstruction of the bony thorax was performed without operative mortality. Since 1980, only patients with four or more ribs resected have had selective bony reconstruction. Follow-up ranged from 8 to 132 months (median follow-up, 42 months). All deaths were related to sarcoma recurrence. The overall actuarial survival rate was 85% at 1 year, 65% at 3 years, and 59% at more than 5 years. The overall actuarial proportion
S
arcomas of soft tissue and bone account for approximately 1%of all malignancies. The chest wall is an uncommon site for sarcoma. Sixty percent 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. Primary neoplasms of the bony chest represent 7% to 8% of all intrinsic bony tumors [ 3 ] .Thus, few patients with chest wall sarcoma are available for evaluation. Sarcomas involving the thorax can originate primarily within the chest wall, represent metastatic disease from a distant site, or develop as a local recurrence from a previously excised chest wall lesion. They occasionally develop in patients previously treated with radiation therapy for malignancies such as breast cancer or Hodgkin's disease [4,51. Aggressive chest wall resection for primary chest wall tumors including sarcomas is well described [3, 6, 71. However, few data are available regarding the appropriate management of patients with metastatic or recurrent chest wall sarcoma. This report compares the results of aggressive treatment of patients with primary, metastatic, or recurrent chest wall sarcomas. Different prognostic factors for disease-free and overall survival were compared to see if such an aggressive approach for patients with metastatic or recurrent chest wall sarcomas is justified. We found no significant difference in overall or Presented at the Twenty-fifth Anniversary Meeting of The Society of Thoracic Surgeons, Baltimore, MD, Sep 11-13, 1989. Address reprint requests to Dr Pass, Thoracic Oncology Section, Surgery Branch, National Cancer InstitutelNlH, Bldg 10, Room 2807, Bethesda, MD 20892. Dr Perry's current address is Department of Surgery, Eastern Virginia Medical School, 825 Fairfax Ave, Norfolk, VA 23507.
without disease recurrence was 64% at 1 year, 52% at 3 years, and 40% at more than 5 years. There was no significant difference in overall or disease-free survival for patients with primary, metastatic, or recurrent tumors. The most important prognostic factors were positive margins and concomitant pulmonary resection for synchronous lung metastases. These data support aggressive resection to obtain pathologically tumor-free margins for chest wall sarcomas, whether primary, metastatic, or recurrent. Reconstruction can be individualized based on the extent of resection. (Ann Thorac Surg 2990;49:363-9)
disease-free survival for patients with primary, metastatic, or recurrent tumors. Factors associated with perioperative morbidity and the need for formal chest wall reconstruction were analyzed. The effect of adjuvant radiation therapy and chemotherapy on patient outcome was examined, and overall management recommendations are made.
Material and Methods The data analyzed originate from 28 patients undergoing resection of chest wall sarcomas in the Surgery Branch of the National Cancer Institute between April 1977 and January 1988. The diagnosis of high-grade sarcoma (grade I1 or 111) was made by the Pathology Department of the National Institutes of Health using established histological criteria [8]. All patients were thought to have disease isolated to the chest wall on the basis of extensive preoperative staging. All patients included in this study were observed for a minimum of 8 months.
Surgical Technique The surgical technique consisted of resection of the entire tumor in monoblock fashion with the aim of achieving pathologically negative margins by careful planning, assisted by intraoperative histological confirmation when in doubt. In all patients, full-thickness excision including the skin (if involved), subcutaneous tissue, and involved portion of the chest wall was performed. At least one uninvolved rib and the interspace above and below the tumor were included with the specimen whenever possible. There was no gross violation of tumor and no visible residual tumor in any patient. Adhesions between the chest wall and pulmonary parenchyma were handled by performing en bloc wedge resection ample enough to
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ensure tumor-free margins without removal of excessive parenchyma. The remainder of the lung parenchyma was carefully palpated for additional nodules, which were excised with tumor-free margins if present [9]. Selective reconstruction was performed using Marlex mesh, a muscle flap, or a Marlex mesh and acrylic "sandwich' [lo] depending on the decision of the operating surgeon. Since 1980, only patients with four or more ribs resected have had selective reconstruction.
Radiotherapy After chest wall resection, 9 adult patients with primary tumors were offered adjuvant radiation therapy as part of a prospective randomized trial for truncal sarcomas [ll]. Patients with metastatic or locally recurrent sarcomas were selectively offered adjuvant radiation therapy. Highdose external-beam radiation therapy was administered using either a 6- or 10-MeV linear accelerator. Radiation volume was determined by review of the preoperative computed tomographic scan of the chest, the operative note, and radiopaque clips placed at the periphery of the operative field. The radiation volume was generally treated isocentrically by using obliquely directed fields determined at simulation. The initial volume was treated to 4,500 rads using 180-rad daily fractions followed by a cone-down boost of 1,800 rads, again using the 180-rad fractions. External-beam irradiation was initiated as soon as the wound was healed, usually within 3 to 4 weeks after operation. The exact techniques used in these patients have been discussed elsewhere [12].
Chemofherapy Patients with primary chest wall tumors and adult histologies (n = 9) received radiotherapy and were randomized to receive or not to receive chemotherapy involving doxorubicin hydrochloride and cyclophosphamide in the Surgery Branch [ll]. Doxorubicin, 70 mg/m2, was administered every 28 days by intravenous bolus. Cyclophosphamide, 700 mg/m2, was administered with doxorubicin every 28 days by intravenous drip over 30 minutes. A total of five cycles were given. Some patients seen early in the series received six cycles of high-dose methotrexate after maximum cumulative doses (500 to 550 mg/m2) of doxorubicin were reached. Patients with metastatic or recurrent chest wall sarcoma of adult histology who had not previously received chemotherapy were offered a similar regimen. Patients with pediatric histologies (osteosarcoma, Ewing's sarcoma, and other round cell tumors) (n = 8) were treated according to Pediatric Oncology Branch protocols. Those with primary tumors were generally treated with vincristine sulfate, doxorubicin, and cyclophosphamide preoperatively. Those with metastatic or recurrent tumors were offered additional chemotherapy whenever possible. Patients who received chemotherapy in conjunction with radiation therapy had the first chemotherapy course three days before the initiation of radiation therapy. Subsequent courses of chemotherapy were administered during and after completion of radiation therapy.
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Patient Follow-up Outpatients were followed at 3-month intervals with complete physical examinations, blood chemistry studies, and chest roentgenograms. Full-lung tomography or computed tomography of the chest was performed every 6 months for 3 years and yearly thereafter. Outpatient follow-up was updated to September 1, 1988.
Statistical Eva1ua t ion Actuarial survival and disease-free survival curves were plotted using the method of Kaplan and Meier [13]. Estimates of survival rates at specific time points were derived from these curves. Comparison of actuarial survival curves was performed using the method of Mantel and Haenszel [14]. All p values reported are two-sided. Factors examined for possible association with time to recurrence and time to death were age at the time of resection, sex, classification of the tumor as primary versus metastatic versus recurrent, the logarithm of tumor volume, the number of ribs involved in resection, treatment with any chemotherapy, treatment with irradiation to the chest wall, postresection margin status, and pulmonary resection for synchronous lung metastases. Because of the long period of accrual of these patients, both a continuous factor (date of chest wall resection) and a dichotomous factor representing the era of resection (resection before 1983 versus resection in or after 1983) were also considered. Combinations of these factors were included in regression analyses using the Cox proportional hazards model [15]. Log rank (Mantel-Haenszel) tests of some individual factors were also performed.
Results The 28 patients, 21 male and 7 female, ranged from 7 to 60 years old (median age, 29 years) at the time of resection. There were 14 primary chest wall sarcomas, 10 metastatic chest wall sarcomas, and 4 recurrent chest wall sarcomas. All tumors were classified as high grade (grade I1 or 111), and included 20 adult soft-tissue sarcomas, 1 childhood rhabdomyosarcoma, 3 Ewing's sarcomas, 3 osteosarcomas, and 1undifferentiated sarcoma. The 20 patients with adult histology were treated according to Surgery Branch protocols and the remaining 8 patients, Pediatric Oncology Branch protocols. Thirty-day operative mortality was 0%. The mean postoperative duration of intubation was 1.2 days (range, zero to eight days). The Spearman rank correlation coefficient between duration of intubation and number of ribs removed was 0.5 ( p < 0.01). The correlation between duration of intubation and need for reconstruction was 0.40 ( p < 0.05). A total of 11patients underwent chest wall reconstruction: 5 with Marlex mesh, 4 with a Marlex mesh and acrylic sandwich, 1 with a muscle flap, and 1 with Marlex mesh and a muscle flap. Since 1984, only patients with resection of four or more ribs have had reconstruction, with 38% (3/8) not undergoing reconstruction. Complications occurred in 36% of patients and consisted predominantly of wound problems (Table 1). The most common wound problem was superficial skin necrosis. Wound complications were more common in patients
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Table 1. Postoperative Complications Complication
No."
Wound problems Deep venous thrombosis Myocardial infarction
7 (25) l(3.6) l(3.6) l(3.6)
Grand ma1 seizureb
10 (35.7)
Total Numbers in parentheses are percentages. of seizure disorder. a
This patient had a history
01
undergoing larger resections; 5 of 14 patients who had four or more ribs resected compared with 2 of 14 patients who had fewer than four ribs resected experienced wound complications. These differences were not significant, however ( p = 0.19). The use of adjuvant or neoadjuvant therapy did not significantly increase the rate of wound complications. The wound complication rate was 33% in those who did not receive any additional therapy, 17% in those who received chemotherapy or radiation therapy or both preoperatively, and 37% in those who received chemotherapy or radiation therapy or both postoperatively. There were no major postoperative pulmonary complications such as pneumonia or respiratory failure. Follow-up ranged from 8 to 132 months (median followup, 42 months). At last follow-up, 18 patients were alive, 13 without sarcoma recurrence. The site of first recurrence after chest wall resection was in the lung in 10 patients, the chest wall in 2 patients, the lung and chest wall in 2 patients, and the retroperitoneum (primary site) in 1 patient. The overall actuarial survival rate was 85% at 1 year, 65% at 3 years, and 59% at more than 5 years (Fig 1). The overall actuarial proportion with no disease recurrence was 64% at 1 year, 52% at 3 years, and 40% at more than 5 years (Fig 2). The factor of overriding importance for survival and recurrence in these patients was margin status. Three patients (2 with metastatic disease and 1 with recurrent disease) had positive margins, and they had the three
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Fig 1. Actuarial curve of overall survival. The overall actuarial survival was 85% at 1 year, 64% at 3 years, and 59% at more than 5 years. The median survival has not yet been reached.
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Fig 2. Actuarial curve of overall recurrence. The overall actuarial proportion free from recurrence was 64% at 1 year, 52% at 3 years, and 40% at more than 5 years.
shortest survival times (5, 7, and 7 months), which was highly significant ( p < 0.001). Margin status did not correlate with tumor type (primary, metastatic, and recurrent) or any other factors including tumor volume. Because all the deaths were due to sarcoma recurrence, margin status was the most important risk factor for recurrence as well. Having positive margins is estimated to increase the relative risk of recurrence by a factor of 8.3 (95% confidence interval, 1.8 to 38). Figures 3 and 4 show the actuarial curves of overall survival and freedom from recurrence stratified by margin status. Patients with negative margins had actuarial long-term survival and recurrence-free survival of 67% and 45%, respectively. No other factors were individually associated with survival or time to recurrence. Specifically, there was no significant difference between patients with primary, metastatic, and recurrent chest wall sarcomas in time to recurrence (Fig 5) and overall survival (Fig 6). In regression models, male patients operated on before 1983 seemed to be at higher risk with a significantly poorer
0
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4 5 6 7 8 Time After Resection (Years) ONegative APositive 7 / 25 Failed 3 / 3 Failed
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Fig 3. Actuarial curves of overall survival stratified by margin status. Patients with positive margins had a mean survival of 6 months. Patients with negative margins had a 67% survival at more than 5 years .
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I I I I I 4 5 6 7 8 Time After Resection (Years A Positive ONegative 12/25 Failed 313 Failed
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Fig 4. Actuarial curves of overall recurrence stratified by margin status. Patients with positive margins had a mean time to recurrence of 4 months. Patients with negative margins had a mean time to recurrence of more than 5 years.
survival (relative risk = 5.8, p < 0.01 for survival) and decreased time to recurrence (relative risk = 3.4, p = 0.01). It must be noted that the 3 patients with positive margins were all in this high-risk group. After the Cox model was adjusted for the effect of positive margins, there remained an increase in the risk of this group for time to recurrence and time to death, although it was of equivocal significance (relative risk = 3.7, p = 0.09 for survival; relative risk = 2.5, p = 0.13 for recurrence). After adjustments were made for both these variables, no other factor improved the fit of the model. This included the variables radiation therapy and chemotherapy. Chemotherapy (9 patients postoperatively and 6 both preoperatively and postoperatively) did not have a significant effecton survival of the entire group (Fig 7), and there was no improvement in survival seen in adults given chemotherapy when the pediatric subgroup was removed from the analysis.
10
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There was no significant difference in overall or diseasefree survival between the adult and pediatric subgroups. With the pediatric subgroup removed from the analysis, the tests for other potential risk factors remained nonsignificant for the adult group except for pulmonary resection for synchronous metastases, which was associated with a significantly higher rate of recurrence (relative risk = 3.9, p = 0.03 by the likelihood ratio test) (Fig 8). Moreover, there was a significant decrease in the overall survival of those adults requiring pulmonary resection ( p = 0.048) (Fig 9).
Comment The role of chest wall resection in the management of primary chest wall tumors is well established. The indications for chest wall resection in the patient with locally recurrent chest wall sarcoma or sarcoma metastatic to the chest wall are less clear. Several large series [3, 6, 71 did
: 10 0
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5 6 7 8 9 10 4 Time After Resection (Years AMetastatic URecurrent OPrimary 61 10 Failed 314 Failed 61 14 Failed 3
Fig 5. Actuarial curves of overall recurrence stratified by type of tumor (primary, metastatic, or recurrent). No significant difference was noted between the tumor types.
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4 5 6 7 8 Time After Resection (Years ) O N 0 Chemotherapy AChemotherapy 6 / 2 0 Failed 418 Failed
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Fig 7 . Actuarial curves of overall survival stratified by chemotherapy status. No significant difference was noted between patients who received chemotherapy and those who did not.
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Fig 8. Actuarial curves of overall recurrence in adults stratified by need for pulmonary resection (Pulm Res) for lung metastases. Those with pulmonary metastases at the time of chest wall resection, even if resection was complete, had a significantly higher recurrence rate (p = 0.03).
not include patients with chest wall sarcoma due to local recurrence or metastatic disease. Others [lo, 161 have shown a role for palliative resection of sarcoma metastatic to the chest wall, although no apparent survival benefit was noted. In the series reported here, there was no significant difference in disease-free survival or overall survival of patients with primary, locally recurrent, or metastatic chest wall sarcomas. The disease-free survival of 40% at more than 5 years and overall survival of 59% at more than 5 years compare favorably with the overall survival of approximately 50% reported by Graeber [6], Sabanathan [3], and their associates for primary chest wall neoplasms and the disease-free survival of 51% reported by Greager and colleagues [7] for primary chest wall sarcomas. Our results differ from those of Pairolero and
..
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E m
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Time After Resection (Years ) oNo Pulm Res APulm Res 3/11 Failed 6 I 9 Failed
Fig 9. Actuarial curves of overall survival in adults stratified by need for pulmona y resection (Pulm Res) for lung metastases. Those with pulmonary metastases at the time of chest wall resection, even if resection was complete, had a significant decrease in survival (p = 0.048).
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Arnold [16], who noted at median follow-up of 31.5 months a survival of 79% for patients with primary chest wall sarcomas and 33% for those with metastatic chest wall sarcomas, findings due most likely to the short follow-up and the inclusion of low-grade sarcomas in their analysis. McCormack and co-workers [lo] reported a 5-year survival of 16.7% for patients with primary chest wall sarcomas and 10% for those with metastatic chest wall sarcomas. Although chest wall resection remains a formidable procedure, it can be performed with low morbidity and mortality, as we and others [3, 6, 7, 16, 171 have shown. In our series, postoperative intubation duration correlated with the extent of chest wall resection. The majority (79%) of patients were removed from ventilatory support in the operating room or by the following morning. However, our population is highly skewed toward the younger age group (mean age, 29 years), and hence most of the patients did not have preexisting pulmonary parenchymal disease. Also unclear are the precise indications for reconstruction of the skeletal defect. Of 155 patients who underwent chest wall resection at Memorial Sloan-Kettering Hospital [lo], 39 required muscle and skin closure alone for a small defect, 8 had closure with ox fascia, 94 had closure with Marlex mesh, and 12, with a Marlex mesh and methyl methacrylate sandwich. The remaining two patients, seen early in the series, had autotransplantation of rib and clavicle. Pairolero and Arnold [18] recommend that, in general, full-thickness skeletal defects of the sternum or lateral thoracic wall be reconstructed with prosthetic material. We have not observed any morbidity or mortality when we have not formally reconstructed defects involving fewer than four ribs. A large number of factors were examined to see if they related to prognosis. The most important factor affecting both disease-free survival and overall survival was margin status, a finding emphasizing the importance of attaining negative margins by a carefully planned procedure, including intraoperative histological confirmation when in doubt. The only other factor significantly affecting the prognosis in adults was the presence of synchronous pulmonary metastases discovered at the time of chest wall resection. Patients with associated pulmonary metastases were found to have a higher chance of recurrence and decreased survival compared with those without pulmonary metastases, despite resection of all disease. That 9 adult patients in our series had pulmonary metastases not discovered during preoperative staging is not surprising. In a recent series of sarcoma patients, only 50% of the nodules found at thoracotomy were seen preoperatively on computed tomography [9]. The role of adjuvant chemotherapy in the management of sarcoma is controversial. One study [19] suggests that adjuvant chemotherapy with doxorubicin and cyclophosphamide with or without methotrexate prolongs diseasefree survival and may prolong overall survival in patients with extremity sarcoma. The benefit for patients with truncal sarcoma is less clear [ l l ] . Our study failed to show any benefit from chemotherapy given to the entire group having chest wall resection. When the patients were
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stratified according to a d u l t o r pediatric histologies, the adult patients still failed to show any benefit from chemotherapy. The results of our s t u d y must be interpreted with caution, however, because of the heterogeneity of the population, differences among the chemotherapeutic agents used and the timing of delivery, and the concomitant use of radiation therapy. We believe that aggressive chest wall resection to achieve negative margins should be performed i n patients w i t h primary, locally recurrent, o r metastatic sarcomas of the chest wall if preoperative staging shows no other disease foci. Bony reconstruction can be individualized based on the extent of resection. There is no significant difference i n disease-free or overall survival among patients with primary, metastatic, or locally recurrent tumors. The m o s t important prognostic factors are margin status and, i n adults, the presence of synchronous pulm o n a r y metastases. The role of chemotherapy i n adult patients and the role of radiation therapy remain unclear. Even though negative margins are achieved, t h e majority of patients will have recurrence either locally or i n the lungs.
References 1. Potter DA, Kinsella T, Glatstein E, et al. High-grade soft tissue sarcomas of the extremities. Cancer 1986;58:190-205. 2. 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: JB Lippincott, 1985:1243-91. 3. Sabanathan S, Salama FD, Morgan WE, Harvey JA. Primary chest wall tumors. Ann Thorac Surg 1985;39:&15. 4. Laskin WB, Silverman TA, Enzinger FM. Postradiation soft tissue sarcomas. Cancer 1988;62:2330-40. 5. Souba WW, McKenna RJ Jr, Meis J, Benjamin R, Raymond AK, Mountain CF. Radiation-induced sarcomas of the chest wall. Cancer 1986;57610-5.
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6. Graeber GM, Snyder RJ, Fleming AW, et al. Initial and long-term results in the management of primary chest wall neoplasms. Ann Thorac Surg 1982;34:664-73. 7. Greager JA, Pate1 MK, Briele HA, Walker MJ, Wood DK, Das Gupta TK. Soft tissue sarcomas of the adult thoracic wall. Cancer 1987;59:370-3. 8. Costa J, Wesley R, Glatstein E, Rosenberg SA. The grading of soft tissue sarcomas. Cancer 1984;53:53&47. 9. Jablons D, Steinberg JM, Roth J, Pittaluga S, Rosenberg SA, Pass HI. Metastasectomy for soft tissue sarcoma. Further evidence of efficacy and prognostic indicators. J Thorac Cardiovasc Surg 1989;97:695-705. 10. McCormack P, Bains MS, Beattie EJ Jr, Martini N. New trends in skeletal reconstruction after resection of chest wall tumors. Ann Thorac Surg 1981;31:45-52. 11. Glenn J, Kinsella T, Glatstein E, et al. A randomized, prospective trial of adjuvant chemotherapy in adults with soft tissue sarcomas of the head and neck, breast, and trunk. Cancer 1985;55:1206-14. 12. Tepper J, Rosenberg SA, Glatstein E. Radiation therapy technique in soft tissue sarcomas of the extremity. Policies of treatment at the National Cancer Institute. Int J Radiat Oncol Biol Phys 1982;8:26%73. 13. Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81. 14. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959;22:71948. 15. Kalbfleisch JC, Prentice RL. The statistical analysis of failure time data. New York: Wiley, 1980. 16. Pairolero PC, Arnold PG. Chest wall tumors. Experience with 100 consecutive patients. J Thorac Cardiovasc Surg 1985;90:367-72. 17. Burnard RJ, Martini N, Beattie EJ Jr. The value of resection in tumors involving the chest wall. J Thorac Cardiovasc Surg 1974;68:53&5. 18. Pairolero PC, Arnold PG. Thoracic wall defects: surgical management of 205 consecutive patients. Mayo Clin Proc 1986;61:557-63. 19. Chang AE, Kinsella T, Glatstein E, et al. Adjuvant chemotherapy for patients with high-grade soft-tissue sarcomas of the extremity. J Clin Oncol 1988;6:1491-500.
DISCUSSION DR VICTOR F. TRASTEK (Rochester, MN): I enjoyed your presentation, Dr Perry, and congratulate you and your colleagues on providing information on a rare but difficult group of 14 patients, in particular those with recurrent or metastatic sarcoma to the chest wall. You have shown acceptable survival and no operative mortality after resection in this group. We also continue to advocate aggressive resection for select patients with recurrent or metastatic disease to the chest wall but only if the primary disease is controlled, the disease is localized and can be completely resected, and the patient can tolerate the procedure. We still believe that rationale for such resection in this group remains controversial but we offer it to these patients because it is the best treatment option we have at this time for these particular patients. Use of intraoperative frozen section analysis and current computed tomography and magnetic resonance scanning should provide margin-free resection of localized disease in most patients. Along these lines, I wonder if you could comment on including 9 patients with synchronous pulmonary metastases
and 3 in whom the margins were positive after resection. Also, could you describe your current preoperative evaluation of both the primary and metastatic process, and how much free margin do you recommend in resections for patients with recurrent or metastatic disease? A successful resection is also dependent on the ability to reconstruct the residual defect resulting in a healed wound. Fullthickness resection usually requires reconstruction of both the bony and soft tissue defect. In your series of 28 patients, 11 had bony reconstruction and only 2 were noted to have some type of soft tissue reconstruction. Although we agree that small bone defects (10 cm) in the skeletal wall do not have to be reconstructed, we do feel that most patients with defects larger than this will benefit from reconstruction to help stabilize the chest wall, provide coverage of thoracic structures, and provide a base for successful soft tissue reconstruction. We have had little morbidity using a prosthetic patch to accomplish this task in a clean wound. Along these lines, could you comment on the cause of wound complications in the 25% of patients in whom they developed?
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DR PERRY 1 certainly agree with Dr Trasteks comments regarding the appropriateness of excising recurrent or metastatic disease in a select group of patients only. I would emphasize that our indications are the same as his: the primary disease must be well controlled if it is a metastatic tumor, the lesion must appear to be resectable with negative margins, and the patient must be able to tolerate the procedure. In terms of our preoperative staging protocol, I am sure it is similar to the type of staging that he does at the Mayo Clinic. We do a careful history and physical examination, and our staging procedures include computerized axial tomography or magnetic resonance imaging, or both. In spite of that, much to our chagrin, there were many patients who had small metastatic deposits discovered at the time of operation. I do not know what else we could have done
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to prevent that from occurring with today's imaging technology. In terms of what our wound complications were, seromas or a little bit of skin necrosis right at the margins of the wound were the most common complications that we saw. I do not know that there is anything that we could have done to prevent those, and I certainly do not think that additional reconstruction of the patients who did not get reconstruction would have prevented those complications. We would disagree with his comments that most patients benefit from formal muscular reconstruction at the time of operation, as we have shown from our data that 38% of patients with large defects did quite well without formal bony reconstruction or muscle flaps. So we think that in select circumstances, depending on the experience and judgment of the surgeon, reconstruction is not always needed.
Indications for chest wall resection of metastatic or locally recurrent sarcoma and for subsequent bony reconstruction are controversial. Twenty-eight patients had chest wall resection for high-grade primary, metastatic, or recurrent sarcoma. In all patients, resection with selective reconstruction of the bony thorax was performed without operative mortality. Since 1980, only patients with four or more ribs resected have had selective bony reconstruction. Follow-up ranged from 8 to 132 months (median follow-up, 42 months). All deaths were related to sarcoma recurrence. The overall actuarial survival rate was 85% at 1 year, 65% at 3 years, and 59% at more than 5 years. The overall actuarial proportion
S
arcomas of soft tissue and bone account for approximately 1%of all malignancies. The chest wall is an uncommon site for sarcoma. Sixty percent 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. Primary neoplasms of the bony chest represent 7% to 8% of all intrinsic bony tumors [ 3 ] .Thus, few patients with chest wall sarcoma are available for evaluation. Sarcomas involving the thorax can originate primarily within the chest wall, represent metastatic disease from a distant site, or develop as a local recurrence from a previously excised chest wall lesion. They occasionally develop in patients previously treated with radiation therapy for malignancies such as breast cancer or Hodgkin's disease [4,51. Aggressive chest wall resection for primary chest wall tumors including sarcomas is well described [3, 6, 71. However, few data are available regarding the appropriate management of patients with metastatic or recurrent chest wall sarcoma. This report compares the results of aggressive treatment of patients with primary, metastatic, or recurrent chest wall sarcomas. Different prognostic factors for disease-free and overall survival were compared to see if such an aggressive approach for patients with metastatic or recurrent chest wall sarcomas is justified. We found no significant difference in overall or Presented at the Twenty-fifth Anniversary Meeting of The Society of Thoracic Surgeons, Baltimore, MD, Sep 11-13, 1989. Address reprint requests to Dr Pass, Thoracic Oncology Section, Surgery Branch, National Cancer InstitutelNlH, Bldg 10, Room 2807, Bethesda, MD 20892. Dr Perry's current address is Department of Surgery, Eastern Virginia Medical School, 825 Fairfax Ave, Norfolk, VA 23507.
without disease recurrence was 64% at 1 year, 52% at 3 years, and 40% at more than 5 years. There was no significant difference in overall or disease-free survival for patients with primary, metastatic, or recurrent tumors. The most important prognostic factors were positive margins and concomitant pulmonary resection for synchronous lung metastases. These data support aggressive resection to obtain pathologically tumor-free margins for chest wall sarcomas, whether primary, metastatic, or recurrent. Reconstruction can be individualized based on the extent of resection. (Ann Thorac Surg 2990;49:363-9)
disease-free survival for patients with primary, metastatic, or recurrent tumors. Factors associated with perioperative morbidity and the need for formal chest wall reconstruction were analyzed. The effect of adjuvant radiation therapy and chemotherapy on patient outcome was examined, and overall management recommendations are made.
Material and Methods The data analyzed originate from 28 patients undergoing resection of chest wall sarcomas in the Surgery Branch of the National Cancer Institute between April 1977 and January 1988. The diagnosis of high-grade sarcoma (grade I1 or 111) was made by the Pathology Department of the National Institutes of Health using established histological criteria [8]. All patients were thought to have disease isolated to the chest wall on the basis of extensive preoperative staging. All patients included in this study were observed for a minimum of 8 months.
Surgical Technique The surgical technique consisted of resection of the entire tumor in monoblock fashion with the aim of achieving pathologically negative margins by careful planning, assisted by intraoperative histological confirmation when in doubt. In all patients, full-thickness excision including the skin (if involved), subcutaneous tissue, and involved portion of the chest wall was performed. At least one uninvolved rib and the interspace above and below the tumor were included with the specimen whenever possible. There was no gross violation of tumor and no visible residual tumor in any patient. Adhesions between the chest wall and pulmonary parenchyma were handled by performing en bloc wedge resection ample enough to
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ensure tumor-free margins without removal of excessive parenchyma. The remainder of the lung parenchyma was carefully palpated for additional nodules, which were excised with tumor-free margins if present [9]. Selective reconstruction was performed using Marlex mesh, a muscle flap, or a Marlex mesh and acrylic "sandwich' [lo] depending on the decision of the operating surgeon. Since 1980, only patients with four or more ribs resected have had selective reconstruction.
Radiotherapy After chest wall resection, 9 adult patients with primary tumors were offered adjuvant radiation therapy as part of a prospective randomized trial for truncal sarcomas [ll]. Patients with metastatic or locally recurrent sarcomas were selectively offered adjuvant radiation therapy. Highdose external-beam radiation therapy was administered using either a 6- or 10-MeV linear accelerator. Radiation volume was determined by review of the preoperative computed tomographic scan of the chest, the operative note, and radiopaque clips placed at the periphery of the operative field. The radiation volume was generally treated isocentrically by using obliquely directed fields determined at simulation. The initial volume was treated to 4,500 rads using 180-rad daily fractions followed by a cone-down boost of 1,800 rads, again using the 180-rad fractions. External-beam irradiation was initiated as soon as the wound was healed, usually within 3 to 4 weeks after operation. The exact techniques used in these patients have been discussed elsewhere [12].
Chemofherapy Patients with primary chest wall tumors and adult histologies (n = 9) received radiotherapy and were randomized to receive or not to receive chemotherapy involving doxorubicin hydrochloride and cyclophosphamide in the Surgery Branch [ll]. Doxorubicin, 70 mg/m2, was administered every 28 days by intravenous bolus. Cyclophosphamide, 700 mg/m2, was administered with doxorubicin every 28 days by intravenous drip over 30 minutes. A total of five cycles were given. Some patients seen early in the series received six cycles of high-dose methotrexate after maximum cumulative doses (500 to 550 mg/m2) of doxorubicin were reached. Patients with metastatic or recurrent chest wall sarcoma of adult histology who had not previously received chemotherapy were offered a similar regimen. Patients with pediatric histologies (osteosarcoma, Ewing's sarcoma, and other round cell tumors) (n = 8) were treated according to Pediatric Oncology Branch protocols. Those with primary tumors were generally treated with vincristine sulfate, doxorubicin, and cyclophosphamide preoperatively. Those with metastatic or recurrent tumors were offered additional chemotherapy whenever possible. Patients who received chemotherapy in conjunction with radiation therapy had the first chemotherapy course three days before the initiation of radiation therapy. Subsequent courses of chemotherapy were administered during and after completion of radiation therapy.
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Patient Follow-up Outpatients were followed at 3-month intervals with complete physical examinations, blood chemistry studies, and chest roentgenograms. Full-lung tomography or computed tomography of the chest was performed every 6 months for 3 years and yearly thereafter. Outpatient follow-up was updated to September 1, 1988.
Statistical Eva1ua t ion Actuarial survival and disease-free survival curves were plotted using the method of Kaplan and Meier [13]. Estimates of survival rates at specific time points were derived from these curves. Comparison of actuarial survival curves was performed using the method of Mantel and Haenszel [14]. All p values reported are two-sided. Factors examined for possible association with time to recurrence and time to death were age at the time of resection, sex, classification of the tumor as primary versus metastatic versus recurrent, the logarithm of tumor volume, the number of ribs involved in resection, treatment with any chemotherapy, treatment with irradiation to the chest wall, postresection margin status, and pulmonary resection for synchronous lung metastases. Because of the long period of accrual of these patients, both a continuous factor (date of chest wall resection) and a dichotomous factor representing the era of resection (resection before 1983 versus resection in or after 1983) were also considered. Combinations of these factors were included in regression analyses using the Cox proportional hazards model [15]. Log rank (Mantel-Haenszel) tests of some individual factors were also performed.
Results The 28 patients, 21 male and 7 female, ranged from 7 to 60 years old (median age, 29 years) at the time of resection. There were 14 primary chest wall sarcomas, 10 metastatic chest wall sarcomas, and 4 recurrent chest wall sarcomas. All tumors were classified as high grade (grade I1 or 111), and included 20 adult soft-tissue sarcomas, 1 childhood rhabdomyosarcoma, 3 Ewing's sarcomas, 3 osteosarcomas, and 1undifferentiated sarcoma. The 20 patients with adult histology were treated according to Surgery Branch protocols and the remaining 8 patients, Pediatric Oncology Branch protocols. Thirty-day operative mortality was 0%. The mean postoperative duration of intubation was 1.2 days (range, zero to eight days). The Spearman rank correlation coefficient between duration of intubation and number of ribs removed was 0.5 ( p < 0.01). The correlation between duration of intubation and need for reconstruction was 0.40 ( p < 0.05). A total of 11patients underwent chest wall reconstruction: 5 with Marlex mesh, 4 with a Marlex mesh and acrylic sandwich, 1 with a muscle flap, and 1 with Marlex mesh and a muscle flap. Since 1984, only patients with resection of four or more ribs have had reconstruction, with 38% (3/8) not undergoing reconstruction. Complications occurred in 36% of patients and consisted predominantly of wound problems (Table 1). The most common wound problem was superficial skin necrosis. Wound complications were more common in patients
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Table 1. Postoperative Complications Complication
No."
Wound problems Deep venous thrombosis Myocardial infarction
7 (25) l(3.6) l(3.6) l(3.6)
Grand ma1 seizureb
10 (35.7)
Total Numbers in parentheses are percentages. of seizure disorder. a
This patient had a history
01
undergoing larger resections; 5 of 14 patients who had four or more ribs resected compared with 2 of 14 patients who had fewer than four ribs resected experienced wound complications. These differences were not significant, however ( p = 0.19). The use of adjuvant or neoadjuvant therapy did not significantly increase the rate of wound complications. The wound complication rate was 33% in those who did not receive any additional therapy, 17% in those who received chemotherapy or radiation therapy or both preoperatively, and 37% in those who received chemotherapy or radiation therapy or both postoperatively. There were no major postoperative pulmonary complications such as pneumonia or respiratory failure. Follow-up ranged from 8 to 132 months (median followup, 42 months). At last follow-up, 18 patients were alive, 13 without sarcoma recurrence. The site of first recurrence after chest wall resection was in the lung in 10 patients, the chest wall in 2 patients, the lung and chest wall in 2 patients, and the retroperitoneum (primary site) in 1 patient. The overall actuarial survival rate was 85% at 1 year, 65% at 3 years, and 59% at more than 5 years (Fig 1). The overall actuarial proportion with no disease recurrence was 64% at 1 year, 52% at 3 years, and 40% at more than 5 years (Fig 2). The factor of overriding importance for survival and recurrence in these patients was margin status. Three patients (2 with metastatic disease and 1 with recurrent disease) had positive margins, and they had the three
2o 10
"
I 2
3
4 5 6 7 8 Time After Resection (Years)
9
10
Fig 1. Actuarial curve of overall survival. The overall actuarial survival was 85% at 1 year, 64% at 3 years, and 59% at more than 5 years. The median survival has not yet been reached.
11
I
I
2
3
I
I
I
I
I
8 Time After Resection (Years 1 4
5
6
7
I
I
I
9 1 0 1 1
Fig 2. Actuarial curve of overall recurrence. The overall actuarial proportion free from recurrence was 64% at 1 year, 52% at 3 years, and 40% at more than 5 years.
shortest survival times (5, 7, and 7 months), which was highly significant ( p < 0.001). Margin status did not correlate with tumor type (primary, metastatic, and recurrent) or any other factors including tumor volume. Because all the deaths were due to sarcoma recurrence, margin status was the most important risk factor for recurrence as well. Having positive margins is estimated to increase the relative risk of recurrence by a factor of 8.3 (95% confidence interval, 1.8 to 38). Figures 3 and 4 show the actuarial curves of overall survival and freedom from recurrence stratified by margin status. Patients with negative margins had actuarial long-term survival and recurrence-free survival of 67% and 45%, respectively. No other factors were individually associated with survival or time to recurrence. Specifically, there was no significant difference between patients with primary, metastatic, and recurrent chest wall sarcomas in time to recurrence (Fig 5) and overall survival (Fig 6). In regression models, male patients operated on before 1983 seemed to be at higher risk with a significantly poorer
0
1
1
1
I
I
2
3
,
I
I
I
I
4 5 6 7 8 Time After Resection (Years) ONegative APositive 7 / 25 Failed 3 / 3 Failed
I
I
9
10
11
Fig 3. Actuarial curves of overall survival stratified by margin status. Patients with positive margins had a mean survival of 6 months. Patients with negative margins had a 67% survival at more than 5 years .
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g
n
+
40-
I
302010
1
I I I I I 4 5 6 7 8 Time After Resection (Years A Positive ONegative 12/25 Failed 313 Failed
I 2
I
3
I 9
1 10
1 11
-
0
I
I
I
I
I
I
I
I
I
I
I
Fig 4. Actuarial curves of overall recurrence stratified by margin status. Patients with positive margins had a mean time to recurrence of 4 months. Patients with negative margins had a mean time to recurrence of more than 5 years.
survival (relative risk = 5.8, p < 0.01 for survival) and decreased time to recurrence (relative risk = 3.4, p = 0.01). It must be noted that the 3 patients with positive margins were all in this high-risk group. After the Cox model was adjusted for the effect of positive margins, there remained an increase in the risk of this group for time to recurrence and time to death, although it was of equivocal significance (relative risk = 3.7, p = 0.09 for survival; relative risk = 2.5, p = 0.13 for recurrence). After adjustments were made for both these variables, no other factor improved the fit of the model. This included the variables radiation therapy and chemotherapy. Chemotherapy (9 patients postoperatively and 6 both preoperatively and postoperatively) did not have a significant effecton survival of the entire group (Fig 7), and there was no improvement in survival seen in adults given chemotherapy when the pediatric subgroup was removed from the analysis.
10
0
I
I
1
2
I
: I
There was no significant difference in overall or diseasefree survival between the adult and pediatric subgroups. With the pediatric subgroup removed from the analysis, the tests for other potential risk factors remained nonsignificant for the adult group except for pulmonary resection for synchronous metastases, which was associated with a significantly higher rate of recurrence (relative risk = 3.9, p = 0.03 by the likelihood ratio test) (Fig 8). Moreover, there was a significant decrease in the overall survival of those adults requiring pulmonary resection ( p = 0.048) (Fig 9).
Comment The role of chest wall resection in the management of primary chest wall tumors is well established. The indications for chest wall resection in the patient with locally recurrent chest wall sarcoma or sarcoma metastatic to the chest wall are less clear. Several large series [3, 6, 71 did
: 10 0
I
I
I
I
I
I
5 6 7 8 9 10 4 Time After Resection (Years AMetastatic URecurrent OPrimary 61 10 Failed 314 Failed 61 14 Failed 3
Fig 5. Actuarial curves of overall recurrence stratified by type of tumor (primary, metastatic, or recurrent). No significant difference was noted between the tumor types.
I 11
1
4 5 6 7 8 Time After Resection (Years ) O N 0 Chemotherapy AChemotherapy 6 / 2 0 Failed 418 Failed
2
3
9
10
11
Fig 7 . Actuarial curves of overall survival stratified by chemotherapy status. No significant difference was noted between patients who received chemotherapy and those who did not.
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Ann Thorac Surg 1990;49:36?-9
10
0
I
1
1
2
I I I I I I 4 5 6 7 8 9 Time After Resection (Years 1 oNo Pulm Res APulm Res 7 / 9 Failed 5 / 11 Failed I
I
3
10
I 11
Fig 8. Actuarial curves of overall recurrence in adults stratified by need for pulmonary resection (Pulm Res) for lung metastases. Those with pulmonary metastases at the time of chest wall resection, even if resection was complete, had a significantly higher recurrence rate (p = 0.03).
not include patients with chest wall sarcoma due to local recurrence or metastatic disease. Others [lo, 161 have shown a role for palliative resection of sarcoma metastatic to the chest wall, although no apparent survival benefit was noted. In the series reported here, there was no significant difference in disease-free survival or overall survival of patients with primary, locally recurrent, or metastatic chest wall sarcomas. The disease-free survival of 40% at more than 5 years and overall survival of 59% at more than 5 years compare favorably with the overall survival of approximately 50% reported by Graeber [6], Sabanathan [3], and their associates for primary chest wall neoplasms and the disease-free survival of 51% reported by Greager and colleagues [7] for primary chest wall sarcomas. Our results differ from those of Pairolero and
..
:I
E m
20
10
Time After Resection (Years ) oNo Pulm Res APulm Res 3/11 Failed 6 I 9 Failed
Fig 9. Actuarial curves of overall survival in adults stratified by need for pulmona y resection (Pulm Res) for lung metastases. Those with pulmonary metastases at the time of chest wall resection, even if resection was complete, had a significant decrease in survival (p = 0.048).
367
Arnold [16], who noted at median follow-up of 31.5 months a survival of 79% for patients with primary chest wall sarcomas and 33% for those with metastatic chest wall sarcomas, findings due most likely to the short follow-up and the inclusion of low-grade sarcomas in their analysis. McCormack and co-workers [lo] reported a 5-year survival of 16.7% for patients with primary chest wall sarcomas and 10% for those with metastatic chest wall sarcomas. Although chest wall resection remains a formidable procedure, it can be performed with low morbidity and mortality, as we and others [3, 6, 7, 16, 171 have shown. In our series, postoperative intubation duration correlated with the extent of chest wall resection. The majority (79%) of patients were removed from ventilatory support in the operating room or by the following morning. However, our population is highly skewed toward the younger age group (mean age, 29 years), and hence most of the patients did not have preexisting pulmonary parenchymal disease. Also unclear are the precise indications for reconstruction of the skeletal defect. Of 155 patients who underwent chest wall resection at Memorial Sloan-Kettering Hospital [lo], 39 required muscle and skin closure alone for a small defect, 8 had closure with ox fascia, 94 had closure with Marlex mesh, and 12, with a Marlex mesh and methyl methacrylate sandwich. The remaining two patients, seen early in the series, had autotransplantation of rib and clavicle. Pairolero and Arnold [18] recommend that, in general, full-thickness skeletal defects of the sternum or lateral thoracic wall be reconstructed with prosthetic material. We have not observed any morbidity or mortality when we have not formally reconstructed defects involving fewer than four ribs. A large number of factors were examined to see if they related to prognosis. The most important factor affecting both disease-free survival and overall survival was margin status, a finding emphasizing the importance of attaining negative margins by a carefully planned procedure, including intraoperative histological confirmation when in doubt. The only other factor significantly affecting the prognosis in adults was the presence of synchronous pulmonary metastases discovered at the time of chest wall resection. Patients with associated pulmonary metastases were found to have a higher chance of recurrence and decreased survival compared with those without pulmonary metastases, despite resection of all disease. That 9 adult patients in our series had pulmonary metastases not discovered during preoperative staging is not surprising. In a recent series of sarcoma patients, only 50% of the nodules found at thoracotomy were seen preoperatively on computed tomography [9]. The role of adjuvant chemotherapy in the management of sarcoma is controversial. One study [19] suggests that adjuvant chemotherapy with doxorubicin and cyclophosphamide with or without methotrexate prolongs diseasefree survival and may prolong overall survival in patients with extremity sarcoma. The benefit for patients with truncal sarcoma is less clear [ l l ] . Our study failed to show any benefit from chemotherapy given to the entire group having chest wall resection. When the patients were
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stratified according to a d u l t o r pediatric histologies, the adult patients still failed to show any benefit from chemotherapy. The results of our s t u d y must be interpreted with caution, however, because of the heterogeneity of the population, differences among the chemotherapeutic agents used and the timing of delivery, and the concomitant use of radiation therapy. We believe that aggressive chest wall resection to achieve negative margins should be performed i n patients w i t h primary, locally recurrent, o r metastatic sarcomas of the chest wall if preoperative staging shows no other disease foci. Bony reconstruction can be individualized based on the extent of resection. There is no significant difference i n disease-free or overall survival among patients with primary, metastatic, or locally recurrent tumors. The m o s t important prognostic factors are margin status and, i n adults, the presence of synchronous pulm o n a r y metastases. The role of chemotherapy i n adult patients and the role of radiation therapy remain unclear. Even though negative margins are achieved, t h e majority of patients will have recurrence either locally or i n the lungs.
References 1. Potter DA, Kinsella T, Glatstein E, et al. High-grade soft tissue sarcomas of the extremities. Cancer 1986;58:190-205. 2. 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: JB Lippincott, 1985:1243-91. 3. Sabanathan S, Salama FD, Morgan WE, Harvey JA. Primary chest wall tumors. Ann Thorac Surg 1985;39:&15. 4. Laskin WB, Silverman TA, Enzinger FM. Postradiation soft tissue sarcomas. Cancer 1988;62:2330-40. 5. Souba WW, McKenna RJ Jr, Meis J, Benjamin R, Raymond AK, Mountain CF. Radiation-induced sarcomas of the chest wall. Cancer 1986;57610-5.
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6. Graeber GM, Snyder RJ, Fleming AW, et al. Initial and long-term results in the management of primary chest wall neoplasms. Ann Thorac Surg 1982;34:664-73. 7. Greager JA, Pate1 MK, Briele HA, Walker MJ, Wood DK, Das Gupta TK. Soft tissue sarcomas of the adult thoracic wall. Cancer 1987;59:370-3. 8. Costa J, Wesley R, Glatstein E, Rosenberg SA. The grading of soft tissue sarcomas. Cancer 1984;53:53&47. 9. Jablons D, Steinberg JM, Roth J, Pittaluga S, Rosenberg SA, Pass HI. Metastasectomy for soft tissue sarcoma. Further evidence of efficacy and prognostic indicators. J Thorac Cardiovasc Surg 1989;97:695-705. 10. McCormack P, Bains MS, Beattie EJ Jr, Martini N. New trends in skeletal reconstruction after resection of chest wall tumors. Ann Thorac Surg 1981;31:45-52. 11. Glenn J, Kinsella T, Glatstein E, et al. A randomized, prospective trial of adjuvant chemotherapy in adults with soft tissue sarcomas of the head and neck, breast, and trunk. Cancer 1985;55:1206-14. 12. Tepper J, Rosenberg SA, Glatstein E. Radiation therapy technique in soft tissue sarcomas of the extremity. Policies of treatment at the National Cancer Institute. Int J Radiat Oncol Biol Phys 1982;8:26%73. 13. Kaplan E, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81. 14. Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst 1959;22:71948. 15. Kalbfleisch JC, Prentice RL. The statistical analysis of failure time data. New York: Wiley, 1980. 16. Pairolero PC, Arnold PG. Chest wall tumors. Experience with 100 consecutive patients. J Thorac Cardiovasc Surg 1985;90:367-72. 17. Burnard RJ, Martini N, Beattie EJ Jr. The value of resection in tumors involving the chest wall. J Thorac Cardiovasc Surg 1974;68:53&5. 18. Pairolero PC, Arnold PG. Thoracic wall defects: surgical management of 205 consecutive patients. Mayo Clin Proc 1986;61:557-63. 19. Chang AE, Kinsella T, Glatstein E, et al. Adjuvant chemotherapy for patients with high-grade soft-tissue sarcomas of the extremity. J Clin Oncol 1988;6:1491-500.
DISCUSSION DR VICTOR F. TRASTEK (Rochester, MN): I enjoyed your presentation, Dr Perry, and congratulate you and your colleagues on providing information on a rare but difficult group of 14 patients, in particular those with recurrent or metastatic sarcoma to the chest wall. You have shown acceptable survival and no operative mortality after resection in this group. We also continue to advocate aggressive resection for select patients with recurrent or metastatic disease to the chest wall but only if the primary disease is controlled, the disease is localized and can be completely resected, and the patient can tolerate the procedure. We still believe that rationale for such resection in this group remains controversial but we offer it to these patients because it is the best treatment option we have at this time for these particular patients. Use of intraoperative frozen section analysis and current computed tomography and magnetic resonance scanning should provide margin-free resection of localized disease in most patients. Along these lines, I wonder if you could comment on including 9 patients with synchronous pulmonary metastases
and 3 in whom the margins were positive after resection. Also, could you describe your current preoperative evaluation of both the primary and metastatic process, and how much free margin do you recommend in resections for patients with recurrent or metastatic disease? A successful resection is also dependent on the ability to reconstruct the residual defect resulting in a healed wound. Fullthickness resection usually requires reconstruction of both the bony and soft tissue defect. In your series of 28 patients, 11 had bony reconstruction and only 2 were noted to have some type of soft tissue reconstruction. Although we agree that small bone defects (10 cm) in the skeletal wall do not have to be reconstructed, we do feel that most patients with defects larger than this will benefit from reconstruction to help stabilize the chest wall, provide coverage of thoracic structures, and provide a base for successful soft tissue reconstruction. We have had little morbidity using a prosthetic patch to accomplish this task in a clean wound. Along these lines, could you comment on the cause of wound complications in the 25% of patients in whom they developed?
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DR PERRY 1 certainly agree with Dr Trasteks comments regarding the appropriateness of excising recurrent or metastatic disease in a select group of patients only. I would emphasize that our indications are the same as his: the primary disease must be well controlled if it is a metastatic tumor, the lesion must appear to be resectable with negative margins, and the patient must be able to tolerate the procedure. In terms of our preoperative staging protocol, I am sure it is similar to the type of staging that he does at the Mayo Clinic. We do a careful history and physical examination, and our staging procedures include computerized axial tomography or magnetic resonance imaging, or both. In spite of that, much to our chagrin, there were many patients who had small metastatic deposits discovered at the time of operation. I do not know what else we could have done
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to prevent that from occurring with today's imaging technology. In terms of what our wound complications were, seromas or a little bit of skin necrosis right at the margins of the wound were the most common complications that we saw. I do not know that there is anything that we could have done to prevent those, and I certainly do not think that additional reconstruction of the patients who did not get reconstruction would have prevented those complications. We would disagree with his comments that most patients benefit from formal muscular reconstruction at the time of operation, as we have shown from our data that 38% of patients with large defects did quite well without formal bony reconstruction or muscle flaps. So we think that in select circumstances, depending on the experience and judgment of the surgeon, reconstruction is not always needed.