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Surgical Treatment of Metastatic Sarcoma to the Lung
Symposium on Surgical Oncology
Surgical Treatment of Metastatic Sarcoma to the Lung
Nael Martini, M.D_,* Manjit S. Bains, MD.,t Andrew G. Huvos, MD_,t and Edward J. Beattie, Jr., MD.§
Sarcomas in general tend to metastasize to lung first in preference to other areas. Resection of these pulmonary metastases when feasible has resulted in prolonged survival, even when these metastases were multiple or bilateral. Such operative procedures presupposed the absence of other effective means of treatment. The present study reviews our experience with the surgical treatment of all types of sarcoma which have metastasized to the lung.
MATERIAL AND METHODS From 1965 to 1972 inclusive, 102 patients with sarcoma were offered surgical treatment for their pulmonary metastases. The different histologic types encountered are shown in Table 1. Excluded from the study were sarcomas of lymphoid or myeloid origin because of available effective therapy by nonsurgical means. The most common tumors treated were osteogenic sarcomas, fibrosarcomas, synovial sarcomas, and myosarcomas. There was an equal overall sex distribution except in leiomyosarcoma. The sites of the primary disease are illustrated in Figure 1 and the age distribution with each tumor type is shown in Figure 2. Treatment of the primary lesion was by resection alone in 85 patients and by resection and external irradiation in 17 patients. Three patients had additional chemotherapy for their primary tumor. The free interval between treatment of the initial tumor and detection of pulmonary metastases was variable with each tumor type. It was From the Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York ., Attending Surgeon, Thoracic Service t Associate Attending Surgeon, Thoracic Service :Associate Attending Pathologist, Department of Pathology §Chief Medical Officer, Attending Surgeon, and Chief, Thoracic Service
Surgical Clinics of North America - VoL 54, No.4, August 1974
841
842
MARTINI, BAINS,
Huvos,
AND BEATTIE,
Table 1. Types of Sarcomas with Sex Incidence MALE
Osteogenic sarcoma Chondrosarcoma Fibrosarcoma" Synovial sarcoma Myosarcoma Rhabdomyosarcoma t Leiomyosarcoma: Liposarcoma Alveolar soft part sarcoma Malignant schwannoma Angiosarcoma ,',
TOTAL
FEMALE
25
25
50 1 12 10
1
7 7
5 3
5 3 2 2 2
4 6 2
9 9 4 3 3
54
48
102
"Includes two patients with malignant fibrous histiocytoma. tFour embryonal and five pleomorphic. tSix originated in uterus and three at other sites,
- Tongue
, SKELETAL
Figure L
TOTAL
SOFT TISSUE
Location of the primary tumor.
JR,
843
SURGICAL TREATMENT OF METASTATIC SARCOMA TO THE LUNG
'1I"'!'iil!!:
.
-------,
OSTEOGENIC SARCOMA CHONDROSARCOMA
FIBROSARCOMA
SYNOVIAL SARCOMA
~
RHABDOMYOSARCOMA
• I' .
LEIOMYOSARCOMA LIPOSARCOMA ALVEOLAR SOFT PART SARCOMA SCHWANNOMA
ANGIOSARCOMA I 0
I 10
I 20
I 30
I
40
50
I 60
I 70
YEARS
Figure 2.
Age incidence at the time of the first thoracotomy.
shorter in osteogenic sarcoma and rhabdomyosarcoma and longer in synovial sarcoma, malignant schwannoma, and alveolar soft part sarcoma. (Table 2). Pulmonary metastases were solitary in 27 patients and multiple in 75 patients (Table 3). Of the latter group 37 had multiple lesions in only one lung with none in the opposite lung and 35 had bilateral multiple pulmonary nodules. Three patients presented with one metastasis in each lung at initial thoracotomy. Most patients (80/102 or 78 per cent) had no symptoms at the time of diagnosis of their pulmonary metastases. Cough, dyspnea, chest pain, and hemoptysis were the predominant symptoms in the remainder (Table Table 2.
Free Interval between Treatment of the Primary Tumor and Detection of Lung Metastasis
Osteogenic sarcoma Chondrosarcoma Fibrosarcoma Synovial sarcoma Rhabdomyosarcoma Leiomyosarcoma Liposarcoma Alveolar soft part sarcoma Malignant schwannoma Angiosarcoma
AVERAGE
MEDIAN
RANGE
(in months)
(in months)
(in months)
8
13
35 60 16 45 24 114 69
30 30 12 14 24 60 72
o to 82
~1
! (.:~
2 12 4 7 10 24 18
50 to 84 to 144 to 36 to 264 to 26 to 144 to 72 15
844
MARTINI, BAINS,
Huvos,
AND BEATTIE, JR.
Table 3. Description of Pulmonary Metastases Unilateral solitary Bilateral solitary Unilateral multiple Bilateral multiple TOTAL
Table 4.
27 3 37 35 102
Symptoms in 22 Patients with Pulmonary Metastases Chest pain Hemoptysis Cough Dyspnea
12 6 8
5
Table 5. Extent of Surgical Treatment (102 Patients) 16
Exploration and biopsy Wedge resection or segmentectomy' Lobectomy Pneumonectomy 1211 implant Lobectomy plus 121 I implant Total procedures
149 22 6 5 2 200
Total number of nodules removed
361
*Extended resection or implantation was carried out only in the slow-growing types of sarcomas.
Table 6.
Number of Thoracotomies Performed per Patient during the Course of His Illness
NUMBER OF THORACOTOMIES
TOTALS
NUMBER OF PATIENTS
1 2
31 31
3 4 5 6
14 6
7
2 1
184
86
SURGICAL TREATMENT OF METASTATIC SARCOMA TO THE LUNG
845
4). These symptoms usually resulted from delay in diagnosis of the pulmonary metastases. They generally reflected endobronchial disease, pleural involvement, or compromise of lung parenchyma by a large bulky tumor or by the extensive multiplicity of the metastases. All patients were surgically explored. In 16 patients the disease was found too extensive to permit resection of all visible tumors and the thoracotomy was confined to exploration and biopsy only. All 16 patients had bilateral multiple pulmonary metastases at initial presentation. Surgical removal of all metastases was possible in 86 patients. The extent of resection necessary is shown in Table 5. A total of 361 nodules were resected from 86 patients at the time of initial treatment. The maximum number of nodules removed at anyone thoracotomy was 13 and at a bilateral thoracotomy 21. The size of each metastatic nodule was recorded in all but four patients at initial thoracotomy (98 patients). When the metastasis was solitary (27 patients), the tumor size varied from 1 to 10 cm, with an average and a median size of 4 cm. When metastases were multiple at initial thoracotomy, tumor size varied from 1 mm to 8 cm, with the majority ranging between 1 and 3 cm. At initial treatment, bilateral thoracotomy was necessary to eradicate all visible tumor in 19 patients, whereas one thoracotomy was sufficient in 67 patients. Recurrence of pulmonary metastases necessitated additional thoracotomies in 36 patients. Some developed extensive recurrence of their pulmonary metastases and were not re-explored. Each patient required an average of two thoracotoniies in the course of his disease, with a range from one to 7 thoracotomies. The number of thoracotomies required per patient is shown in Table 6. Of 200 thoracotOInies performe~, ere were five postoperative deaths. Three of these were secondarY'- 0 atrial and mediastinal involvement by tumor resulting in cardiac f ure. One patient died from pneumonia 13 days following a pneumon~tomy and one patient died of pulmonary embolus. In addition to surgical resection of the metastases, other forms of treatment were carried out in some of the patients, singly or in combination. Twenty-five patients, all with osteogenic sarcoma, received autologous vaccine prepared from their tumor. Thirty-three patients with various types of sarcoma received intensive systeInic chemotherapy. Ten patients had external irradiation to chest wall, spine, or other sites of skeletal metastases, but not to lung. One patient with osteogenic sarcoma also received immunotherapy. All the survival results presented are calculated from the date of the first thoracotomy for lung metastasis. Figure 3 summarizes the survival in the 16 patients when pulmonary metastases could not be removed. Only two of the patients, one with fibrosarcoma and one with leiomyosarcoma, survived 5 years. The former died of brain metastasis, and the latter is still alive with disease in the lung at 65 months. Survival time in this group was poorest in those with osteogenic sarcoma and rhabdomyosarcoma. Of 86 patients in whom resection of all detectable tumor in the lung was possible at the initial presentation, 15 are alive free of disease, 17 are alive with disease, one died of postoperative pulmonary embolus without
846
MARTINI, BAINS,
Huvos,
AND BEATTIE, JR.
Months from diagnosis of metastases • = Dead 0= Alive Figure 3.
Survival in patients with unresected metastases.
residual tumor, and the rest died of recurrence or metastases. The most common sites of disease at death were lung and bone (Table 7). Brain metastasis or local recurrence at the primary site were less commonly noted. Local recurrence occurred in sarcomas other than osteogenic sarcomas. Survival in patients with resected pulmonary metastases has been calculated by the life table method, the results of which are shown in Figure 4. No patient was lost to follow-up. All patients were available for at least 1 year follow-up, 61 patients were available for a 3 year follow-up, and 35 patients for 5 year follow-up. Overall survival was best in patients with alveolar soft part sarcoma and malignant schwannoma, with two of three in each category alive and well at 5 years, and poorest with rhabdomyosarcoma, with none alive at 2 years.
DISCUSSION Several years ago there was very little treatment offered for patients with bilateral multiple pulmonary metastases from sarcomas. Resection was used in select instances on individuals with a solitary metastasis who had proved to remain free of disease for prolonged periods of time after the treatment of of the primary tumor. Both radiation therapy and chemotherapy were of little avail and only in the exceptional patient was
Table 7.
Common Sites of Metastases at Death
Lung Bone Brain Local recurrence
43 12
4 6
847
SURGICAL TREATMENT OF METASTATIC SARCOMA TO THE LUNG
\
\
\ \
-Alive - - AI ive. free of tumor
\ \ \
~%
"I:
'*
*
\
.~
30%
.......
20
23% .........-._
20"10
20%
170f,
~_""-----' _ _ . . . .
0
Years
Figure 4.
Survival in patients with resected metastases (86 patients).
there any response to either mode of treatment. The data presented here represent an aggressive surgical approach to eradicate pulmonary metastases, primarily in patients whose primary tumor had been controlled. It will be noted that in the patients treated by resection, there was a continued drop in survival during the first 3 years after treatment. Survival rate beyond that period has leveled off with a 26 per cent survival in patients at risk for 5 years. In the intervening years, we have learned that vigorous treatment with chemotherapeutic agents such as methotrexate and adriamycin also has beneficial effects in sarcoma. There is also evidence that radiotherapy for local control of the disease is potentiated when used in association with vigorous chemotherapy. Additionally, there is increased awareness and interest in the immune status of the patient and the possibility that immunotherapy may prove to be a valuable mode of treatment. At the present time, we favor a clinical investigative study combining surgery with these adjuvants. It would seem reasonable that in many situations at least one operation would be necessary to establish the diagnosis and to be certain of the extent of disease. It is possible that if these other forms of treatment become more effective, surgery will be indicated for those lesions which continue to grow or are not controlled by nonsurgical means.
REFERENCES 1. Evans, A. E.: Mitomycin C. Cancer Chemother. Rep., 14:1,1961. 2. Francis, K. C., Hutter R. V., Phillips, R. K., Eyerle, R. C., and Schechter, L.: Osteogenic sarcoma: Sustained disappearance of pulmonary metastases after only palliative irradiation. New Eng. J. Med., 266:694, 1962.
848
MARTINI, BAINS,
Huvos,
AND BEATTIE, JR.
3. Jaffe, N., Farber, S., Traggis, D., Geiser, C., Kim, B. S., Das, L., Frauenberger, G., Djerassi, L, and Cassady, J. R.: Favorable responses of metastatic osteogenic sarcoma to pulse high dose methotrexate with citrovorum rescue in radiation therapy. Cancer, 31: 1367-1371, 1973. 4. Martini, N., Huvos, A. G., Mike, V., Marcove, R. C., and Beattie, E. J.: Multiple pulmonary resections in the treatment of osteogenic sarcoma. Ann. Thorac. Surg., 12:271-280, 1971. 5. Tan, C., Etcubanas, R., Wollner, N., Rosen, G., Gilladoga, A., Schowel, J., Murphy, M. L., and Krakoff, L H.: Adriamycin-an antitumor antibiotic in the treatment of neoplastic diseases. Cancer, 32:9-17, 1973. 444 East 68th Street New York, New York 10021
Surgical Treatment of Metastatic Sarcoma to the Lung
Nael Martini, M.D_,* Manjit S. Bains, MD.,t Andrew G. Huvos, MD_,t and Edward J. Beattie, Jr., MD.§
Sarcomas in general tend to metastasize to lung first in preference to other areas. Resection of these pulmonary metastases when feasible has resulted in prolonged survival, even when these metastases were multiple or bilateral. Such operative procedures presupposed the absence of other effective means of treatment. The present study reviews our experience with the surgical treatment of all types of sarcoma which have metastasized to the lung.
MATERIAL AND METHODS From 1965 to 1972 inclusive, 102 patients with sarcoma were offered surgical treatment for their pulmonary metastases. The different histologic types encountered are shown in Table 1. Excluded from the study were sarcomas of lymphoid or myeloid origin because of available effective therapy by nonsurgical means. The most common tumors treated were osteogenic sarcomas, fibrosarcomas, synovial sarcomas, and myosarcomas. There was an equal overall sex distribution except in leiomyosarcoma. The sites of the primary disease are illustrated in Figure 1 and the age distribution with each tumor type is shown in Figure 2. Treatment of the primary lesion was by resection alone in 85 patients and by resection and external irradiation in 17 patients. Three patients had additional chemotherapy for their primary tumor. The free interval between treatment of the initial tumor and detection of pulmonary metastases was variable with each tumor type. It was From the Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York ., Attending Surgeon, Thoracic Service t Associate Attending Surgeon, Thoracic Service :Associate Attending Pathologist, Department of Pathology §Chief Medical Officer, Attending Surgeon, and Chief, Thoracic Service
Surgical Clinics of North America - VoL 54, No.4, August 1974
841
842
MARTINI, BAINS,
Huvos,
AND BEATTIE,
Table 1. Types of Sarcomas with Sex Incidence MALE
Osteogenic sarcoma Chondrosarcoma Fibrosarcoma" Synovial sarcoma Myosarcoma Rhabdomyosarcoma t Leiomyosarcoma: Liposarcoma Alveolar soft part sarcoma Malignant schwannoma Angiosarcoma ,',
TOTAL
FEMALE
25
25
50 1 12 10
1
7 7
5 3
5 3 2 2 2
4 6 2
9 9 4 3 3
54
48
102
"Includes two patients with malignant fibrous histiocytoma. tFour embryonal and five pleomorphic. tSix originated in uterus and three at other sites,
- Tongue
, SKELETAL
Figure L
TOTAL
SOFT TISSUE
Location of the primary tumor.
JR,
843
SURGICAL TREATMENT OF METASTATIC SARCOMA TO THE LUNG
'1I"'!'iil!!:
.
-------,
OSTEOGENIC SARCOMA CHONDROSARCOMA
FIBROSARCOMA
SYNOVIAL SARCOMA
~
RHABDOMYOSARCOMA
• I' .
LEIOMYOSARCOMA LIPOSARCOMA ALVEOLAR SOFT PART SARCOMA SCHWANNOMA
ANGIOSARCOMA I 0
I 10
I 20
I 30
I
40
50
I 60
I 70
YEARS
Figure 2.
Age incidence at the time of the first thoracotomy.
shorter in osteogenic sarcoma and rhabdomyosarcoma and longer in synovial sarcoma, malignant schwannoma, and alveolar soft part sarcoma. (Table 2). Pulmonary metastases were solitary in 27 patients and multiple in 75 patients (Table 3). Of the latter group 37 had multiple lesions in only one lung with none in the opposite lung and 35 had bilateral multiple pulmonary nodules. Three patients presented with one metastasis in each lung at initial thoracotomy. Most patients (80/102 or 78 per cent) had no symptoms at the time of diagnosis of their pulmonary metastases. Cough, dyspnea, chest pain, and hemoptysis were the predominant symptoms in the remainder (Table Table 2.
Free Interval between Treatment of the Primary Tumor and Detection of Lung Metastasis
Osteogenic sarcoma Chondrosarcoma Fibrosarcoma Synovial sarcoma Rhabdomyosarcoma Leiomyosarcoma Liposarcoma Alveolar soft part sarcoma Malignant schwannoma Angiosarcoma
AVERAGE
MEDIAN
RANGE
(in months)
(in months)
(in months)
8
13
35 60 16 45 24 114 69
30 30 12 14 24 60 72
o to 82
~1
! (.:~
2 12 4 7 10 24 18
50 to 84 to 144 to 36 to 264 to 26 to 144 to 72 15
844
MARTINI, BAINS,
Huvos,
AND BEATTIE, JR.
Table 3. Description of Pulmonary Metastases Unilateral solitary Bilateral solitary Unilateral multiple Bilateral multiple TOTAL
Table 4.
27 3 37 35 102
Symptoms in 22 Patients with Pulmonary Metastases Chest pain Hemoptysis Cough Dyspnea
12 6 8
5
Table 5. Extent of Surgical Treatment (102 Patients) 16
Exploration and biopsy Wedge resection or segmentectomy' Lobectomy Pneumonectomy 1211 implant Lobectomy plus 121 I implant Total procedures
149 22 6 5 2 200
Total number of nodules removed
361
*Extended resection or implantation was carried out only in the slow-growing types of sarcomas.
Table 6.
Number of Thoracotomies Performed per Patient during the Course of His Illness
NUMBER OF THORACOTOMIES
TOTALS
NUMBER OF PATIENTS
1 2
31 31
3 4 5 6
14 6
7
2 1
184
86
SURGICAL TREATMENT OF METASTATIC SARCOMA TO THE LUNG
845
4). These symptoms usually resulted from delay in diagnosis of the pulmonary metastases. They generally reflected endobronchial disease, pleural involvement, or compromise of lung parenchyma by a large bulky tumor or by the extensive multiplicity of the metastases. All patients were surgically explored. In 16 patients the disease was found too extensive to permit resection of all visible tumors and the thoracotomy was confined to exploration and biopsy only. All 16 patients had bilateral multiple pulmonary metastases at initial presentation. Surgical removal of all metastases was possible in 86 patients. The extent of resection necessary is shown in Table 5. A total of 361 nodules were resected from 86 patients at the time of initial treatment. The maximum number of nodules removed at anyone thoracotomy was 13 and at a bilateral thoracotomy 21. The size of each metastatic nodule was recorded in all but four patients at initial thoracotomy (98 patients). When the metastasis was solitary (27 patients), the tumor size varied from 1 to 10 cm, with an average and a median size of 4 cm. When metastases were multiple at initial thoracotomy, tumor size varied from 1 mm to 8 cm, with the majority ranging between 1 and 3 cm. At initial treatment, bilateral thoracotomy was necessary to eradicate all visible tumor in 19 patients, whereas one thoracotomy was sufficient in 67 patients. Recurrence of pulmonary metastases necessitated additional thoracotomies in 36 patients. Some developed extensive recurrence of their pulmonary metastases and were not re-explored. Each patient required an average of two thoracotoniies in the course of his disease, with a range from one to 7 thoracotomies. The number of thoracotomies required per patient is shown in Table 6. Of 200 thoracotOInies performe~, ere were five postoperative deaths. Three of these were secondarY'- 0 atrial and mediastinal involvement by tumor resulting in cardiac f ure. One patient died from pneumonia 13 days following a pneumon~tomy and one patient died of pulmonary embolus. In addition to surgical resection of the metastases, other forms of treatment were carried out in some of the patients, singly or in combination. Twenty-five patients, all with osteogenic sarcoma, received autologous vaccine prepared from their tumor. Thirty-three patients with various types of sarcoma received intensive systeInic chemotherapy. Ten patients had external irradiation to chest wall, spine, or other sites of skeletal metastases, but not to lung. One patient with osteogenic sarcoma also received immunotherapy. All the survival results presented are calculated from the date of the first thoracotomy for lung metastasis. Figure 3 summarizes the survival in the 16 patients when pulmonary metastases could not be removed. Only two of the patients, one with fibrosarcoma and one with leiomyosarcoma, survived 5 years. The former died of brain metastasis, and the latter is still alive with disease in the lung at 65 months. Survival time in this group was poorest in those with osteogenic sarcoma and rhabdomyosarcoma. Of 86 patients in whom resection of all detectable tumor in the lung was possible at the initial presentation, 15 are alive free of disease, 17 are alive with disease, one died of postoperative pulmonary embolus without
846
MARTINI, BAINS,
Huvos,
AND BEATTIE, JR.
Months from diagnosis of metastases • = Dead 0= Alive Figure 3.
Survival in patients with unresected metastases.
residual tumor, and the rest died of recurrence or metastases. The most common sites of disease at death were lung and bone (Table 7). Brain metastasis or local recurrence at the primary site were less commonly noted. Local recurrence occurred in sarcomas other than osteogenic sarcomas. Survival in patients with resected pulmonary metastases has been calculated by the life table method, the results of which are shown in Figure 4. No patient was lost to follow-up. All patients were available for at least 1 year follow-up, 61 patients were available for a 3 year follow-up, and 35 patients for 5 year follow-up. Overall survival was best in patients with alveolar soft part sarcoma and malignant schwannoma, with two of three in each category alive and well at 5 years, and poorest with rhabdomyosarcoma, with none alive at 2 years.
DISCUSSION Several years ago there was very little treatment offered for patients with bilateral multiple pulmonary metastases from sarcomas. Resection was used in select instances on individuals with a solitary metastasis who had proved to remain free of disease for prolonged periods of time after the treatment of of the primary tumor. Both radiation therapy and chemotherapy were of little avail and only in the exceptional patient was
Table 7.
Common Sites of Metastases at Death
Lung Bone Brain Local recurrence
43 12
4 6
847
SURGICAL TREATMENT OF METASTATIC SARCOMA TO THE LUNG
\
\
\ \
-Alive - - AI ive. free of tumor
\ \ \
~%
"I:
'*
*
\
.~
30%
.......
20
23% .........-._
20"10
20%
170f,
~_""-----' _ _ . . . .
0
Years
Figure 4.
Survival in patients with resected metastases (86 patients).
there any response to either mode of treatment. The data presented here represent an aggressive surgical approach to eradicate pulmonary metastases, primarily in patients whose primary tumor had been controlled. It will be noted that in the patients treated by resection, there was a continued drop in survival during the first 3 years after treatment. Survival rate beyond that period has leveled off with a 26 per cent survival in patients at risk for 5 years. In the intervening years, we have learned that vigorous treatment with chemotherapeutic agents such as methotrexate and adriamycin also has beneficial effects in sarcoma. There is also evidence that radiotherapy for local control of the disease is potentiated when used in association with vigorous chemotherapy. Additionally, there is increased awareness and interest in the immune status of the patient and the possibility that immunotherapy may prove to be a valuable mode of treatment. At the present time, we favor a clinical investigative study combining surgery with these adjuvants. It would seem reasonable that in many situations at least one operation would be necessary to establish the diagnosis and to be certain of the extent of disease. It is possible that if these other forms of treatment become more effective, surgery will be indicated for those lesions which continue to grow or are not controlled by nonsurgical means.
REFERENCES 1. Evans, A. E.: Mitomycin C. Cancer Chemother. Rep., 14:1,1961. 2. Francis, K. C., Hutter R. V., Phillips, R. K., Eyerle, R. C., and Schechter, L.: Osteogenic sarcoma: Sustained disappearance of pulmonary metastases after only palliative irradiation. New Eng. J. Med., 266:694, 1962.
848
MARTINI, BAINS,
Huvos,
AND BEATTIE, JR.
3. Jaffe, N., Farber, S., Traggis, D., Geiser, C., Kim, B. S., Das, L., Frauenberger, G., Djerassi, L, and Cassady, J. R.: Favorable responses of metastatic osteogenic sarcoma to pulse high dose methotrexate with citrovorum rescue in radiation therapy. Cancer, 31: 1367-1371, 1973. 4. Martini, N., Huvos, A. G., Mike, V., Marcove, R. C., and Beattie, E. J.: Multiple pulmonary resections in the treatment of osteogenic sarcoma. Ann. Thorac. Surg., 12:271-280, 1971. 5. Tan, C., Etcubanas, R., Wollner, N., Rosen, G., Gilladoga, A., Schowel, J., Murphy, M. L., and Krakoff, L H.: Adriamycin-an antitumor antibiotic in the treatment of neoplastic diseases. Cancer, 32:9-17, 1973. 444 East 68th Street New York, New York 10021