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The role of radiotherapy in the treatment of primary mediastinal seminoma
Radiotherapy and Oncology, 24 (1992) 226-230 © 1992 Elsevier Science Publishers B.V. All rights reserved. 0167-8140/92/$05.00
226 RADION 01023
The role of radiotherapy in the treatment of primary mediastinal seminoma M i n o r u U e m a t s u a, M a k o t o K o n d o b, T a k u s h i D o k i y a c, Seiichi T a m a i d, Y u t a k a A n d o b a n d Shozo Hashimoto b Departments of aRadiology and d Pathology, National Defense Medical College, Saitama, Japan, bDepartment of Radiation Therapy, Keio University School of Medicine, Tokyo, Japan, and ~Department of Radiology, Second Tokyo National Hospital, Tokyo, Japan
(Received 3 June 1991, accepted 8 April 1992)
Key words: Mediastinum; Seminoma; Radiotherapy
Summary Nine patients with primary mediastinal seminoma were treated with radiotherapy. All patients achieved complete response on chest radiography. None of the three patients treated with whole mediastinal irradiation relapsed. Four of the six patients with involved-field irradiation had marginal relapses, suggesting the efficacy of the whole mediastinal irradiation.
Introduction
Primary mediastinal seminoma is rare. Only approximately 300 cases were reported in the English literature since 1951. Because of high radiosensitivity, radiotherapy with or without surgical resection was the treatment of choice for the majority of patients. However, relapses often occurred following radiotherapy. Since primary mediastinal seminoma demonstrated good responses to chemotherapy, we re-evaluated the role of each treatment modality. In this study, we present the results of nine patients treated with radiotherapy, and review the literature in order to discuss treatment options. Materials and methods
Nine patients with primary mediastinal seminoma were treated with radiotherapy between 1969 and 1987. All had an anterior mediastinal tumour on chest radiography. One patient had the left supraclavicular lymph node swelling, and another showed a massive chest
wall invasion. The other seven patients had a localized tumour in the mediastinum. Only one patient had macroscopic complete resection, and the remaining patients had partial resection or biopsy (Table I). Pathologic slides were reviewed in all patients, and revealed pure seminoma. Serum alpha-feto-protein (AFP) and beta-human-chorionic-gonadotropin (BH C G ) were checked in three patients; one showed slight elevation of B-HCG. No patients had a testicular mass or retroperitoneal lymph node enlargement during the course of the disease. Six patients, before 1982, received involved-field irradiation which covered the tumour with narrow margins. In the remaining three patients after 1982, in order to reduce marginal recurrences, whole mediastinal irradiation of 15 Gy was given, to the entire pericardium, diaphragmatic crurae and bilateral supraclavicular fossae. After 15 Gy, heart blocks were used and the fields were gradually reduced. Total radiation doses to the initial tumour site ranged from 30 to 50 Gy given over 3 to 6 weeks using 6 or 10 MV linac X-rays for eight patients. The remaining patient received telecobalt therapy to total dose of
Address for correspondence: Minoru Uematsu M.D., Department of Radiology, National Defense Medical College, 3-2, Namiki, Tokorozawa,
Saitama, 359, Japan.
227 TABLE I Summary of nine patients in the present series. Patient no.
Age/ sex
Symptom
Extramediastinal disease
Biopsy procedure
Radiotherapy fields:Gy
Initial relapse
Other relapse
Treatment for relapse
Outcome (mths.)
1
36/M
-
-
Thoracotomy
IF:16
-
-
-
2
33/M
-
SCLN
Excision
IF:40
Margin
Radiotherapy
3
30/M
Fever
-
Thoracotomy
IF:42
-
Neck LN lung, pericardium -
A & W (230) A & W (225)
4
32/M
Fever
-
Thoracotomy
IF:40
Margin
5
29/F
Cough Dyspnoea
Chest wall
Incision (chest wall)
IF:50
Margin
6
26/M
-
-
Thoracotomy
IF:44
Margin
Axilla LN
7
34/M
-
-
Thoracotomy
WM:45
-
-
Radiotherapy VCR Radiotherapy BLM, A D M , VLB, C P M Radiotherapy C D D P , VLB, BLM -
8
t3/M
-
-
WM:30
-
-
-
9
18/M
SVC
(B-HCG + )
Total resection CT-guided needle
WM:40
-
-
-
Lung, pericardium Liver, pleura
-
A & W (199) D o D (24) D o D (30)
A & W (111) A & W
(88) A & W (60) A & W (40)
M = male; F = female; SVC = superior venacaval syndrome; S C L N = supraclavicular lymph node; CT = computed tomography; B - H C G = beta h u m a n chorionic gonadotropin; I F = i n v o l v e d fields; VCR=vincristine; BLM =bleomycin; A D M =adriamycin; VLB =vinblastine; CPM = cyclophosphamide; C D D P = cis-platinum; A & W = alive and well; D o D = dead of disease; W M = whole mediastinal fields with shrinking field technique.
16 Gy given over 4 days because of the physician preference (Table I).
ment, except that one has suffered from azoospermia caused by salvage PVB chemotherapy.
Results
Discussion
All patients achieved complete resolution of the tumour on chest radiography. None of the three patients treated with whole mediastinal irradiation relapsed with a follow-up of 40 to 88 months. Four of the six patients with involved-field irradiation relapsed at the margin of the radiation fields within 12 months. All the relapsing patients received additional radiotherapy for the marginal recurrence, resulting in temporarily second remission. However, all had second relapses in the pericardium, pleura, cervical or axillary lymph node, lung, or liver. Two patients were salvaged by radiotherapy and/or PVB chemotherapy (20 mg/m 2 of cis-platinum on days 1-5, 0.3 mg/kg of vinblastine on day 1, 10 mg/ m z of bleomycin on days 1, 8, 15), and two died of disease (Table I). As a result, 7 of the 9 patients are alive and well for 40 to 230 months. These seven patients have no remarkable symptoms caused by treat-
The results of the present study, even with the small number of patients, demonstrate the high radiosensitivity of primary mediastinal seminoma and the efficacy of using extended-field irradiation. In order to confirm these findings and discuss the treatment options, we reviewed the English literature. There are more than 300 reported cases, however, they are sometimes without a mention of the treatment, reported twice, or followed-up for very short periods. Thus, including our 9 cases, we chose 179 cases followed-up for at least 24 months or to death or relapse for analysis of treatment results [ 1-9,11-38,40-55,57-59] (Table II). In studying patterns of failure following radiotherapy, in-field recurrences appear rare. Of all patients listed in Table II, only 11 patients had in-field recurrences after radiotherapy [8,21,28,36,43,52]. Moreover, in 7 of the 11 patients, the recurrence seems to be due
228 TABLE II Results of 179 patients in the literature. Local treatment Controlled Failure Salvaged Dead Unknown Surgical death
172 (11 a) i01 (5 a) 64 (6 a) 17 (3 a) 43 (3 a) 4 7
CDDP chemotherapy Controlled
7 (4 b) 7 (4 b)
a Patients with less intensive chemotherapy. b Patients with local irradiation.
to insufficient radiation doses [8,21,36], inadequate technique [43], or secondary metastasis from previously relapsed sites outside the radiation fields [8,52]. Thus, the risk of true in-field recurrence following standard radiotherapy seems to be less than 3 ~ , so that, surgical resection is of no use for local control. Recommended radiation doses varied from 35 to 40 Gy [21,31], except for Bush et al. proposing somewhat higher doses [8]. Currently, we use 40 Gy for a gross tumour. In spite of the high radiosensitivity, one third of patients relapsed following radiotherapy in Table II, with distant metastases or marginal recurrences. Partly based on these patterns of failure, recent reports often used initial cis-platinum containing chemotherapy [25,44,57,58]. Seven patients in Table II received such regimens with or without local irradiation, and were alive and well for more than 24 months. However, it is very questionable that chemotherapy is essential for all patients. Although second malignancy following chemotherapy remains unclear in this disease [39], the risk of pulmonary damage should be increased when chemotherapy is used with mediastinal irradiation [56]. If cured without chemotherapy, patients can avoid the risk of drug-induced pulmonary fibrosis [ 10] or sterility (Patient 6).
In the literature, several authors used extended-field irradiation with excellent results [3,31,34,37]. In a total of 10 cases treated with the extended-field irradiation, there were no relapse except one patient who later had a lumbar vertebral metastasis and was salvaged by chemotherapy and additional radiotherapy [ 31 ]. Including our three patients, the 13 cases with initial extendedfield irradiation showed 9 2 ~ of relapse-free survival and 100 ~o of overall survival. These results confirm the efficacy of using whole mediastinal irradiation presented in this study. On the other hand, Bush et al. reported results of another 13 cases in Stanford University [8]. Despite the fact that the majority of their patients were irradiated to whole mediastinum, the relapse-free survival was 5 4 ~ and overall survival was 69~o at 10 years. These quite different outcomes using similar extended-field irradiation are probably due to the difference in the initial disease extent of each group. Among the 13 cases in the Stanford study; five had cervical or supraclavicular lymph nodes swelling, three showed positive lymphangiogram, one had a chest wall mass, and a few had pulmonary parenchymal involvement at the initial presentation [8]. However, such advanced presentations were not common in the group with favourable results [3,31,34,37]. Therefore, these findings should be judged as poor prognostic factors following radiotherapy alone. We believe that patients with a localized tumour in the mediastinum are curable with whole mediastinal irradiation alone. More advanced disease should be treated with intensive chemotherapy with or without local irradiation. For this rare malignancy, national or international studies are necessary in order to decide the further optimal management.
Acknowledgements We thank Drs. Peter M. Mauch and Mark Langer (Joint Center for Radiation Therapy, Boston, MA) for helpful advice.
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51 52
53 54
55
diastinum. Cancer Control Agency of British Columbia experience. Cancer 55: 450-452, 1985. Luna, M . A . and Tamariz, J.V. Germ cell tumors of the mediastinum. Postmortem findings. AJCP 65: 450-454, 1976. Martini, N., Golbey, R. B., Hajda, S. I. et al. Primary mediastinal germ cell tumors. Cancer 33: 763-769, 1974. McCombs, R. K., Singhi, V. and Olson, W . H . Primary mediastinal seminoma and the gallium-67 total body scan: A case report. J. Urol. 126: 560-562, 1981. Medini, E., Levitt, S. H., Jones, T. K. et al. The management of extratesticular seminoma without gonadal involvement. Cancer 44: 2032-2038, 1979. Melillo, N. G., Orsini, J. and Safirsteim B. Primary mediastinal seminoma presenting as superior vena cava obstruction. New Jersey Med. 83: 173-174, 1986. Moriconi, W., Taylor, S., Huntracoon, M. et al. Primary mediastinal germinoma in females: A case report and review of the literature. J. Surg. Oncol. 29: 176-180, 1985. Nazari, A. and Gagnon, E.D. Seminoma*like tumor of the mediastinum. A case report with 7-year follow-up. J. Thorac. Cardiovasc. Surg. 51: 751-754, 1966. Nichols, C. R., Hoffman, R., Einhorm, L. H., Williams, S. D., Wheeler, L. A. and Garnick, M . B . Hematologic malignancies associated with primary mediastinal germ cell tumors. Ann. Intern. Med. 102: 603-609, 1985. Nickles, J. and Franssila, K. Primary seminoma of the anterior mediastinum. A case report with 10-year follow-up Acta Path. Microbiol. Scand. 80: 260-262, 1972. Oberman, H . A . and Libcke, J . H . Malignant germinal neoplasms of the mediastinum. Cancer 17: 498-507, 1964. O'Gara, R. W., Horn, R. C., Jr. and Enterline, H . T . Tumors of the anterior mediastinum. Cancer 11: 562-590, 1958. Pachter, M. R. and Lattes, R. Germinal tumors of the mediastinum: A clinicopathological study of adult teratomas, teratocarcinomas, choriocarcinomas and seminomas. Dis. Chest 45: 301-310, 1964. Pandy, K.J. and Chang, Y. Cure of mediastinal seminoma. Ann. Intern. Med. 97: 618, 1982. Polansky, S. M., Barwick, K. W. and Ravin, C.E. Primary mediastinal seminoma. AJR 132: 17-21, 1979. Raghavan, D. and Barret, A. Mediastinal seminomas. Cancer 46: 1187-1191, 1980. Rao, K. K., Rao, B. N., Balasundaram, V. et al. Primary mediastinal seminoma. Indian J. Cancer 18: 153-156, 1981. Recondo, J. and Libshitz, H.I. Mediastinal extragonadal germ cell tumors. Urology l l: 369-375, 1978. Robinson, B.W. Germinal neoplasia of extragenital origin. J. Natl. Med. Assoc. 52: 162-165, 1960. Schantz, A., Sewali, W, and Castleman, B. Mediastinal germinoma: A study of 21 cases with an excellent prognosis. Cancer 30: 1189-1194, 1972. Shields, T.W., Fox, R.T. and Lee, M . W . Thymic tumors. Classification and treatment. Arch. Surg. 92: 617-622, 1966. Steinmetz, W . H . and Hay, R.A. Primary seminoma of the mediastinum: Report of a case with an unusual site of metastasis and review of the literature. AJR 86: 669-672, 1961. Sterchi, M. and Cordell, A.R. Seminoma of the anterior mediastinum. Ann. Thorac. Surg. 19: 371-377, 1975. Taira, Y., Osada, H., Yokote, K. et al. Primary mediastinal seminoma: Report of three cases and literature review. Jpn. J. Cancer Chemother. 40: 455-461, 1987. Taniguchi, H., Pai, T. J. and Amakata, Y. Two cases of semi-
230 nomatous tumor originating from the anterior mediastinum. Gann 48: 639-641, 1957. 56 Tarbell, N. J., Thompson, L. and Mauch, P.M. Thoracic irradiation in Hodgkin's disease; Disease control and long-term complications. Int. J. Radiat. Oncol. Biol. Phys. 18: 275-281, 1990. 57 Tawa, A., Hara, J., Yumura, K. et al. Successful chemotherapy
for mediastinal seminoma: A case report. Jpn. J. Cancer Chemother. 11: 1687-1691, 1984. 58 Wakabayashi, T., Sasaki, T., Yanagisawa, M. et al. A case of primary mediastinal seminoma. Jpn. J. Thorac. Surg. 34: 634636, 1981. 59 Ximenes-Neto, M. and Agostini, A.A. Primary seminoma of the mediastinum. Int. J. Surg. 59: 425-427, 1974.
226 RADION 01023
The role of radiotherapy in the treatment of primary mediastinal seminoma M i n o r u U e m a t s u a, M a k o t o K o n d o b, T a k u s h i D o k i y a c, Seiichi T a m a i d, Y u t a k a A n d o b a n d Shozo Hashimoto b Departments of aRadiology and d Pathology, National Defense Medical College, Saitama, Japan, bDepartment of Radiation Therapy, Keio University School of Medicine, Tokyo, Japan, and ~Department of Radiology, Second Tokyo National Hospital, Tokyo, Japan
(Received 3 June 1991, accepted 8 April 1992)
Key words: Mediastinum; Seminoma; Radiotherapy
Summary Nine patients with primary mediastinal seminoma were treated with radiotherapy. All patients achieved complete response on chest radiography. None of the three patients treated with whole mediastinal irradiation relapsed. Four of the six patients with involved-field irradiation had marginal relapses, suggesting the efficacy of the whole mediastinal irradiation.
Introduction
Primary mediastinal seminoma is rare. Only approximately 300 cases were reported in the English literature since 1951. Because of high radiosensitivity, radiotherapy with or without surgical resection was the treatment of choice for the majority of patients. However, relapses often occurred following radiotherapy. Since primary mediastinal seminoma demonstrated good responses to chemotherapy, we re-evaluated the role of each treatment modality. In this study, we present the results of nine patients treated with radiotherapy, and review the literature in order to discuss treatment options. Materials and methods
Nine patients with primary mediastinal seminoma were treated with radiotherapy between 1969 and 1987. All had an anterior mediastinal tumour on chest radiography. One patient had the left supraclavicular lymph node swelling, and another showed a massive chest
wall invasion. The other seven patients had a localized tumour in the mediastinum. Only one patient had macroscopic complete resection, and the remaining patients had partial resection or biopsy (Table I). Pathologic slides were reviewed in all patients, and revealed pure seminoma. Serum alpha-feto-protein (AFP) and beta-human-chorionic-gonadotropin (BH C G ) were checked in three patients; one showed slight elevation of B-HCG. No patients had a testicular mass or retroperitoneal lymph node enlargement during the course of the disease. Six patients, before 1982, received involved-field irradiation which covered the tumour with narrow margins. In the remaining three patients after 1982, in order to reduce marginal recurrences, whole mediastinal irradiation of 15 Gy was given, to the entire pericardium, diaphragmatic crurae and bilateral supraclavicular fossae. After 15 Gy, heart blocks were used and the fields were gradually reduced. Total radiation doses to the initial tumour site ranged from 30 to 50 Gy given over 3 to 6 weeks using 6 or 10 MV linac X-rays for eight patients. The remaining patient received telecobalt therapy to total dose of
Address for correspondence: Minoru Uematsu M.D., Department of Radiology, National Defense Medical College, 3-2, Namiki, Tokorozawa,
Saitama, 359, Japan.
227 TABLE I Summary of nine patients in the present series. Patient no.
Age/ sex
Symptom
Extramediastinal disease
Biopsy procedure
Radiotherapy fields:Gy
Initial relapse
Other relapse
Treatment for relapse
Outcome (mths.)
1
36/M
-
-
Thoracotomy
IF:16
-
-
-
2
33/M
-
SCLN
Excision
IF:40
Margin
Radiotherapy
3
30/M
Fever
-
Thoracotomy
IF:42
-
Neck LN lung, pericardium -
A & W (230) A & W (225)
4
32/M
Fever
-
Thoracotomy
IF:40
Margin
5
29/F
Cough Dyspnoea
Chest wall
Incision (chest wall)
IF:50
Margin
6
26/M
-
-
Thoracotomy
IF:44
Margin
Axilla LN
7
34/M
-
-
Thoracotomy
WM:45
-
-
Radiotherapy VCR Radiotherapy BLM, A D M , VLB, C P M Radiotherapy C D D P , VLB, BLM -
8
t3/M
-
-
WM:30
-
-
-
9
18/M
SVC
(B-HCG + )
Total resection CT-guided needle
WM:40
-
-
-
Lung, pericardium Liver, pleura
-
A & W (199) D o D (24) D o D (30)
A & W (111) A & W
(88) A & W (60) A & W (40)
M = male; F = female; SVC = superior venacaval syndrome; S C L N = supraclavicular lymph node; CT = computed tomography; B - H C G = beta h u m a n chorionic gonadotropin; I F = i n v o l v e d fields; VCR=vincristine; BLM =bleomycin; A D M =adriamycin; VLB =vinblastine; CPM = cyclophosphamide; C D D P = cis-platinum; A & W = alive and well; D o D = dead of disease; W M = whole mediastinal fields with shrinking field technique.
16 Gy given over 4 days because of the physician preference (Table I).
ment, except that one has suffered from azoospermia caused by salvage PVB chemotherapy.
Results
Discussion
All patients achieved complete resolution of the tumour on chest radiography. None of the three patients treated with whole mediastinal irradiation relapsed with a follow-up of 40 to 88 months. Four of the six patients with involved-field irradiation relapsed at the margin of the radiation fields within 12 months. All the relapsing patients received additional radiotherapy for the marginal recurrence, resulting in temporarily second remission. However, all had second relapses in the pericardium, pleura, cervical or axillary lymph node, lung, or liver. Two patients were salvaged by radiotherapy and/or PVB chemotherapy (20 mg/m 2 of cis-platinum on days 1-5, 0.3 mg/kg of vinblastine on day 1, 10 mg/ m z of bleomycin on days 1, 8, 15), and two died of disease (Table I). As a result, 7 of the 9 patients are alive and well for 40 to 230 months. These seven patients have no remarkable symptoms caused by treat-
The results of the present study, even with the small number of patients, demonstrate the high radiosensitivity of primary mediastinal seminoma and the efficacy of using extended-field irradiation. In order to confirm these findings and discuss the treatment options, we reviewed the English literature. There are more than 300 reported cases, however, they are sometimes without a mention of the treatment, reported twice, or followed-up for very short periods. Thus, including our 9 cases, we chose 179 cases followed-up for at least 24 months or to death or relapse for analysis of treatment results [ 1-9,11-38,40-55,57-59] (Table II). In studying patterns of failure following radiotherapy, in-field recurrences appear rare. Of all patients listed in Table II, only 11 patients had in-field recurrences after radiotherapy [8,21,28,36,43,52]. Moreover, in 7 of the 11 patients, the recurrence seems to be due
228 TABLE II Results of 179 patients in the literature. Local treatment Controlled Failure Salvaged Dead Unknown Surgical death
172 (11 a) i01 (5 a) 64 (6 a) 17 (3 a) 43 (3 a) 4 7
CDDP chemotherapy Controlled
7 (4 b) 7 (4 b)
a Patients with less intensive chemotherapy. b Patients with local irradiation.
to insufficient radiation doses [8,21,36], inadequate technique [43], or secondary metastasis from previously relapsed sites outside the radiation fields [8,52]. Thus, the risk of true in-field recurrence following standard radiotherapy seems to be less than 3 ~ , so that, surgical resection is of no use for local control. Recommended radiation doses varied from 35 to 40 Gy [21,31], except for Bush et al. proposing somewhat higher doses [8]. Currently, we use 40 Gy for a gross tumour. In spite of the high radiosensitivity, one third of patients relapsed following radiotherapy in Table II, with distant metastases or marginal recurrences. Partly based on these patterns of failure, recent reports often used initial cis-platinum containing chemotherapy [25,44,57,58]. Seven patients in Table II received such regimens with or without local irradiation, and were alive and well for more than 24 months. However, it is very questionable that chemotherapy is essential for all patients. Although second malignancy following chemotherapy remains unclear in this disease [39], the risk of pulmonary damage should be increased when chemotherapy is used with mediastinal irradiation [56]. If cured without chemotherapy, patients can avoid the risk of drug-induced pulmonary fibrosis [ 10] or sterility (Patient 6).
In the literature, several authors used extended-field irradiation with excellent results [3,31,34,37]. In a total of 10 cases treated with the extended-field irradiation, there were no relapse except one patient who later had a lumbar vertebral metastasis and was salvaged by chemotherapy and additional radiotherapy [ 31 ]. Including our three patients, the 13 cases with initial extendedfield irradiation showed 9 2 ~ of relapse-free survival and 100 ~o of overall survival. These results confirm the efficacy of using whole mediastinal irradiation presented in this study. On the other hand, Bush et al. reported results of another 13 cases in Stanford University [8]. Despite the fact that the majority of their patients were irradiated to whole mediastinum, the relapse-free survival was 5 4 ~ and overall survival was 69~o at 10 years. These quite different outcomes using similar extended-field irradiation are probably due to the difference in the initial disease extent of each group. Among the 13 cases in the Stanford study; five had cervical or supraclavicular lymph nodes swelling, three showed positive lymphangiogram, one had a chest wall mass, and a few had pulmonary parenchymal involvement at the initial presentation [8]. However, such advanced presentations were not common in the group with favourable results [3,31,34,37]. Therefore, these findings should be judged as poor prognostic factors following radiotherapy alone. We believe that patients with a localized tumour in the mediastinum are curable with whole mediastinal irradiation alone. More advanced disease should be treated with intensive chemotherapy with or without local irradiation. For this rare malignancy, national or international studies are necessary in order to decide the further optimal management.
Acknowledgements We thank Drs. Peter M. Mauch and Mark Langer (Joint Center for Radiation Therapy, Boston, MA) for helpful advice.
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