Radiotherapy in stage IIA and IIB testicular seminoma with reduced portals: A prospective multicenter study

PI1 SO360-3016(97)00155-7

0 Clinical Investigation RADIOTHERAPY IN STAGE HA AND HB TESTICULAR SEMINOMA WITH REDUCED PORTALS: A PROSPECTIVE MULTICENTER STUDY HEINZ SCHMIDBERGER, * MICHAEL BAMBERG,* CHRISTOF MEISNER, -’ JOHANNES CLASSEN, * CORNELIA WINKLER, $ MICHAEL HARTMANN, s RAINER TEMPLIN, ii THOMAS WEGEL. y WOLFGANG DORNOFF,’ DIETER Ross, * * HANS-J• ACHIM THIEL. F CARMEN MARTINI, F+AND WULF HAASE ’ Departments of Radiotherapy: *Tubingen, *Dresden, “Schwerin, *Berlin-Benjamin Franklin, ‘Trier, * *Koln. ” Barnberg, 7V5reiburg. ‘Karlsruhe: ‘Institute for Medical Information Processing,Tubingen. qDepartment of Urology BWK Hamburg. Ciermany Purpose: A prospective multicenter study was cat-tied out to esthnate the treatment outcome of radlotherapy in Stage II seminoma after the application of modern stag& and radIotherapy techniques. The lower margin of the iliac tield was positioned on the upper rim of the acetabulum to reduce the amount of scattered irradiation to the remah&tg testicle. Methods and Materlals: The study was cart-led out in 25 centers in Germany. Patients with pure semlnoma, ne8atlve A&P-v&es, and retroperltoneal lymph node metastases of lessthan 5 cm ht diameter were entered into the study. All path&s received a ventrodorsal opposed field irradlatlon of the lymph nodes. The llehls extended from the top of the 11th thoraclc vertebra to in Stage IL4 (lymph nodes <2 cm ) received 30 Gy, and patients with Stage IIB (lymph nodes between 2 and 5 cm) 36 Gy total dose. Resultsz 39 patients in Stage IIA and 19 patients lu Stage IIB were evaluated. After a median observatlou time of 37 months all patlents are alive and diseasefree. Recurrence free survival ln stage IIA was 100%. Two patients in Stage IIB experienced a recurrence 10 and 17 mouths after the end of radiotherapy. The actuarial racurrence free survival estimate in Stage IIB was 94.1% for 1 year and 87.4% for 2 years. One recurrence in Stage IIB occurred in the medlastinmn, one in the mediastinum, and one the lung. Both patients could be salvagad by chemotherapy. There were no pelvic recurrences. The treatment was well tolerated, with nausea being the most common side effect (56.9% Grade 1, 15.5% Grade 2, and 8.6% Grade 3). Diarrhea occurred in 15.5% iGrade 1), 15.5% (Grade 2), and 5.2% (Grade 3) of the patients. Conchrsmns: The outcome of para-aortlc and ipsllateral iliac irradmtion lu Stage DA/B testicular seminoma is excellent wlth the currently avalhtble staging methods and treatment facllltles. The treatment is well tolerated. The lower margin of the iliacal field can be placed at the acetabulum. 0 1997 Elsevler Science Inc. Seminoma, Testicular cancer, Testicular neoplasm, Radiotherapy, Stage II, Portals, Side effects, Radiation effects.

INTRODUCTION The treatment of Stage II testicular seminoma has been unaltered for many years. After the orchiectomy, the paraaortic and the ipsilateral iliac lymph nodes are irradiated through ventrodorsal opposed fields. Elective mediastinal irradiation for this disease was discontinued by most centers, because potent chemotherapy became available for salvage treatment (5, 7, 12, 13, 27, 33, 35), and mediastinal irradiation impaired the bone marrow reserve for subsequent chemotherapy (6, 17 ) . Data from the Royal Marsden Hospital indicated, that retroperitoneal disease of more than 5 cm in diameter carries a bad prognosis if radiotherapy is administered as sole treatment (5). In patients with para-aortic lymph node disease <2 cm in diameter (Stage IIA), relapse occured in 9.4%. For those Reprint requests to: Dr. Heinz Schmidberger, Department of Radiotherapy. Robert-Koch-Str. 40. 37085 G&tingen, Germany.

with disease 2 to 5 cm in diameter (Stage IIB), the relapse rate was 18.2%. and for those with disease >S cm (Stage

IIC ) it was 39.1% (5 ) . The authors proposed that all patients with retroperitoneal

disease of more than S cm in

diameter should be treated with chemotherapy. The standard treatment of retroperitoneal disease less than 5 cm in diameter remained the irradiation of the para-aortic and the ipsiiateral iliacal nodes. Table 1 shows the results of

studies reported over the past 20 years on radiotherapy in testicular seminoma with retroperitoneal disease of less than 5 cm in diameter. As Stage II testicular seminoma is a rare disease, there are only a few patients with this condition treated per year in most centers, making it difficult to compiie monocentric

data on treatment outcome ( 39 ). Accordingly, most of the Accepted

for publication

20 March I997

322

I. .I. Radiation Oncology 0 Biology 0 Physics

Volume 39, Number 2, 1997

Table 1. Radiotherapy in Stage IIA/B seminoma (retroperitoneal lymphoma <5 cm)

Author/reference Andrews et al. (4) Abdeen et al. (3) Ball et aZ. (5) Duncan et al. (10) Epstein et al. (11) Gregory et al. (14) Hunter et al. (16) Kellokumpu-L&men et al. (17) Lai et al. (18) Lederman et al. (20) Lester et al. (21) Mason et al. (24) Sagerman et al (29) Yeoh et al. (38)

Time of treatment

No. of patients

(1962-1984) (1972-1987) (1963- 1979) (1970-1981) (1975-1987) (1970- 1984) (1964-1984)

17

(1970-1982) (1964-1988) (1968-1984) (1961-1981) (1968-1985) (1966- 1985) (1981-1990)

:: 40 16 39 15 66 33 25 i; 21 8

Median follow-up @=4

Recurrentfree survival WI

Dose @Y)

Lower field margin

8.7 6.2 8.8 5.75 5.5 6.3 9.0

94% 93% 88% 75% 100% 87% 100%

N.A. 25 + 10 30 + 10 30 30 + 6 35 33.3

N.A. lower border of the obturator foramen mid obturator foramen lower border of the obturator foramen symphysis pubis mid obturator foramen N.A.

6.7 6.0 6.0 6.2 8.5 6.75

87% 93% 96% 80% 96% 90% 100%

35 34 30 29.3 30 + 6 30 34.7

N.A. N.A. lower border of the obturator fommen pelvic ischium lower border of the obturator foramen N.A. N.A.*

N.A.: data not available; Mediastinal irradiation was given to the majority of patients in all series. * No mediastinal irradiation in this series.

reported series are retrospective reports, which cover a large time period of patient accrual with heterogeneous treatment policies (Table 1) . The development of modem staging procedures during the time of patient accrural (CT scans, MRI, tumor markers) have additionally led to inhomogeneities in the treated patient populations (33). Therefore, it is difficult in the absence of firm data to define a treatment policy for radiotherapy in Stage II testicular seminoma that would reflect state-of-the-art radiotherapy. We have conducted a multicenter clinical study to evaluate the outcome as well as the acute side effects of standard para-aortic and ipsilateral iliac irradiation in patients with Stage IIA and IIB testicular seminoma, according to the Royal Marsden Classification (5). In contrast to the published reports, we chose to position the inferior border of the portal to the upper rim of the acetabulum to reduce the scattered radiation to the remaining testicle. Most other studies used the midobturator foramen or the bottom of the obturator foramen as a landmark for the lower field margin. In the following report we will present the interim analysis of our study after a median follow up of 37 months. PATIENTS Participating

AND METHODS

centers and investigators

The study protocol was approved by 25 participating centers (see Appendix). Patient selection

Patients with pure testicular seminoma in clinical Stage IIA and IIB (according to the Royal Marsden Classification (5), and a negative level of APP prior to orchiectomy were admitted to the study.

During the first year of the study, only patients with negative preoperative levels of p-HCG were admitted, as at that time it was assumed, that p-HCG-positive tumors would carry a different prognosis. During the second and third year of the study patients with raised ,&HCG levels of up to 200 IU/l were admitted as well, because two large studies had pointed out that the prognosis of patients is not affected by the initial ,&HCG levels (25, 37). All patients were asked for informed consent according to the declaration of Helsinki. Patients with a history of prior radiotherapy or prior chemotherapy were excluded. Radiation jields

Radiotherapy was applied through ventrodorsal opposed fields with 4-20 MV photons of linear accelerators. Treatment with “Co was not allowed. The “hockeystick” fields, covering the para-aortic and the ipsilateral iliac nodes were simulated according to the following guidelines: the upper field margin projected on the cranial rim of the 1 lth thoracic vertebra, the lower field margin projected on the cranial rim of the acetabulum. The lateral field margins for the para-aortic region were defined by the ends of the lateral vertebral processes, resulting in a width of the fields between 9 and 11 cm. The lateral borders for the iliac region were defined by a line from the upper rim of the acetabulum to the end lateral process of the fourth lumbar vertebra. The para-aortic and iliacal regions were treated in one field by using individualized absorbers. Both opposed fields were treated every day for 5 days per week with fractions of 2.0 Gy per day as specified in the ICRU 29 report for opposing fields. A total dose of 30 Gy was applied in Stage IIA. In Stage Ill3 the dose was increased to 36 Gy. A boost treatment was not performed.

Radiotherapy in Stage IIA and B testicular seminoma l

Staging procedures The minimal requirements for the staging of the patients consisted of an abdominal CT-scan and a chest x-ray, or a CT-scan of the thorax. The preoperative serum level of AFP was determined in all patients. Evuluation of treatment Follow-up examinations were planned every 3 months for the first 2 years after radiotherapy. Thereafter, the intervals were lengthened to 6 months between each visit. Clinical examination and the determination of AFP and p-HCG levels had to be performed at each visit. Abdominal CT-scans were taken twice a year for the first 2 years, and annually thereafter. Abdominal ultrasound was performed alternating with abdominal CT-scans (twice a year during the first 2 years, once a year after the second year). Chest x-rays were taken every 3 months for the first 2 years and every 6 months thereafter. Documentation of recurrences Recurrent tumor sites were investigated by CT or MRI images. The CT and MRI films were compared with the initial simulation films of the individual patient to determine how the lesion was localized relative to the radiation field. Morlitoring of side effects The acute side effects (nausea, intestinal, and cutaneous side effects ) during radiotherapy were monitored and recorded according to the EORTC/WHO-scores. A sperm count was obtained prior to radiotherapy and 1 and 2 years after radiotherapy in patients who agreed to this additional testing, Data monitoring The pathohistologic, diagnostic, therapeutic, and follow-up data were recorded on specially prepared forms and entered into a computerized database at the coordinating center (University of Ti.ibingen) using the study monitoring system of the Institute for Medical Information Processing (IMI) . All data were monitored by the coordinating center. After the closing of the database for this interim analysis (December 3 lst, 1996) all data were transfemed to the IMI for further data processing. The statistical analysis was made for descriptive purposes. Continuous variables are described by use of statistical characteristics (means ?Z standard deviations). Discrete variables are described as counts and percentages. The recurrence free survival was estimated by the actuarial method. For the statistical analysis the database was converted into SAS-files and the SAS-System (SAS 6.08 for Windows) was used. RESULTS

Between April 1991 and March 1994 a total of 92 patients were enrolled into the study. Thirty-four patients

H. SCHMEDBERGER

?r ~1.

32.3

were excluded from the interim analysis due to one or more omitted inclusion criteria or protocol violations ( 17 patients had a level of AFP above the limit prior to orchiectomy, in 14 patients radiotherapy was not strictly adherent to the protocol, 6 patients were lost to follow up, 3 patients had treatment with “‘Co. 2 patients had no chest x-ray or CT-scan of the thorax prior to radiotherapy, 1 patient had no abdominal CT-scan prior to orchiectomy, 2 patients had too many missing data. One anaplastic seminoma had to be reclassified as high-grade lymphoma upon lymphatic tumor recurrence ) . Of the remaining 58 patients in the study 39 presented with Stage IIA and 19 patients presented with Stage IIB disease. The median time of follow up is 37 months. Thirty-five patients (60.3% ) had their last follow up in 1996. Therefore, 49 patients (34 in Stage IIA ) were observed for a minimum of 12 months and 41 (28 in Stage IIA) for a minimum of 24 months. The median age of the patients was 32 years, the mean age was 34.3 ( 59.7) years with a range from 20 to 63 years. The right testicle was affected in 24 (4 1.4% ) of the cases. in 34 (58.6%) the left testicle was the primdry tumor site. Histopathology Fifty-six patients (96.6%) presented with classical seminoma, I patient ( 1.7%) with spermatocytic seminoma. 1 tumor ( I .7%) was classified as anaplastic seminoma. Tumor stage was Tl in 44 patients (7S.9%), T2 in 12 patients (20.7% ), and T3 in 2 patients ( 3.45~ 1. Staging All evaluated patients received an abdominal CT-scan. A bipedal lymphangiogram was performed additionally in 41.4 7%, and an abdominal ultrasound in ~56.9% of the patients. The mediastinal nodes were analyzed by a chest x-ray in 93.1% and/or a CT-scan of the thorax in 7S.9%* of all cases. Seven patients ( 12.1%) had an increased semm level of &HCG. Eight out of 25 patients tested had an increase of serum lactate dehydrogenase (LDH ) prior to orchiectomy. Side eflects Mild nausea ( Grade I) was observed in 56.9% of the patients and was the most common adverse effect (Table 2). Complaints from 15.5% were of transient vomiting (Grade 2 ) . Grade 3 nausea ( vomiting requiring therapy ) occurred in 8.6% of the patients. Some of the patients ( 15.5% ) noted increased bowel movements or diarrhoea for less than 2 days. Some ( 15.5% ) experienced Grade 2 diarrhoea, and 5.2% Grade 3 diarrhoea. The acute cutaneous side effects were ahnost negligible with erythema in 15.5% of the patients. No patient experienced skin changes that were higher than Grade I. Late side effects were observed only in 1 patient, who showed a slight hyperpigmentation of the skin in the radiation field. There were no subcutaneous fibrosis and no gastrointestinal late effects reported”

324

I. J. Radiation Oncology l Biology 0 Physics

Table 2. Acute maximal side effects of radiotherapy Grade Nausea 0 2 3 4 Diarrhea 0 1 2 3 4

Cutaneous 0 1 2 3 4

Definition (EORTC-SCOX) None Nausea Transient

vomiting

Vomiting requiring therapy Intractable vomiting None Transient

(<2 days)

Tolerable, (but >2 days) Intolerable, requiring therapy Haemorrhagic, dehydration None Erythema Dry desquamation Moist desquamation Necrosis

No. of patients

%

11 33 9 5 0

19.0 56.9 15.5 8.6 0

37 9 9 3

63.8 15.5 15.5 5.2

0

0

49 9

84.5 15.5

0 0 0

0 0 0

Therapeutic eflcacy All patients treated are currently alive and disease free. In two patients a mediastinal relapse was observed. One of these patients additionally had lung metastases. Both patients had initially III3 disease. In both cases a complete remission was achieved by salvage chemotherapy (Table 3 ) . One of the two patients received a thoracotomy because of a residual mass larger than 3 cm after three cycles of PEB-chemotherapy. The histologic examination of the tumor specimen showed no viable tumor cells. The actuarial disease free survival estimate in Stage IL4 was lOO%, in Stage IIB it was 94.1% (95% confidence interval: 82.9100) for the first year and 87.4% (95% confidence interval: 71.0- 100) for 2 years. In Stage IIA/B together it was 98.1% (95% confidence interval: 94.5-100) for 1 and 96% (95% confidence interval: 90.4-100) for 2 years. Overall survival was 100 for Stage IL4 and IIB. A contralateral neoplasm has not been observed so far.

DISCUSSION The interim analysis of our study is indicating that the overall survival in Stage IIA/B testicular seminoma treated with para-aortic and ipsilateral iliacal irradiation approaches 100%. The recurrent free survival is 100% in Stage IIA, and 87.4% in Stage IIB at 2 years. The median observation in our study is 37 months. Although late recurrences have been observed in testicular seminoma, a further dramatic increase of the reccurrence rate is unlikely to occur, because “Wait and See” studies in Stage I testicular seminoma have shown that the median time to recurrence in seminoma is somewhere in between 14 and 16 months (23,26, 30,36). Our results are somewhat better than the reported historic series for lymph node disease ~5 cm, summarized

Volume 39, Number 2, 1997

in Table 1. The patients in our series were staged carefully with the currently available imaging techniques and tumor markers. Radiotherapy was performed exclusively with linear accelerators, using a simulator for planning and custom shaped absorbers during tberapy. Therefore, our results could be considered as representative for the outcome of tbe treatment with modern techniques, whereas the results of the historical studies are representing the technical status of the sixties, the seventies, and the eighties. During this time period several important advances have been made in the management of testicular cancer: the bipedal lymphangiography has been largely replaced by CT-scanning. The preoperative determination of APP allowed to exclude nonseminomatous tumors or mixed germ cell tumors, that had histologically been misclassified as pure seminomas. The mCo treatment units have been replaced by linear accelerators. The introduction of treatment simulators allowed to place the portals exactly in reference to anatomical landmarks. Duncan and Munroe ( 10) already noticed in their series that the survival of patients increased during the study period. The studies summarized in Table 1 are indicating a similar trend. There is a tendency to increased recurrent free survival in more recent studies compared to earlier studies. Compiled data showed that mediastinal relapse occurred only in 8 out of 250 patients after subdiaphragmatic irradiation in Stage IIA (34). In our patients we observed two mediastinal recurrences, which approximates the expected 3% rate of tbe compiled data. The two patients with mediastinal relapse could be salvaged successfully with polychemotherapy. Therefore, we do not recommend mediastinal irradiation in Stage IIA/B testicular seminoma. This has been pointed out in earlier reports by Ball (5) and Thomas (34). The disadvantages of mediastinal irradiation in testicular seminoma are an increased incidence of coronary artery disease in tbe treated patients ( 19, 32) and a limitation of the bone marrow reserve for further salvage chemotherapy (6,12- 14). More recently, mediastinal or supraclavicular irradiation has been advocated for testicular seminoma with retroperitoneal lymphonodular disease larger than 5 cm, because mediastinal relapses are more common in bulky abdominal disease. (9, 32). In this stage of the disease we would recommend to perform initial polychemotherapy (5, 7, 22, 27) for the above-mentoned reasons. Because both mediastinal recurrences occurred in Stage IIB, it could be argued that patients in this stage would profit from primary chemotherapy as well. However, 87.4% of the patients in Stage IIB, who survived without a recurrence, could be treated with very low side effects. It would not be justified to increase the side effects in all patients by applying primary chemotherapy to possibly avoid a recurrence in 12.6% of the patients. This is particularly true, because both patients with mediastinal recurrences could be salvaged successfully by polychemotberapy. The acute side effects have been remarkably low in our study. Only 8.6% of the patients suffered from Grade 3

Radiotherapy in Stage

IIA

and B testicular seminoma

0 H. SCHMIDBERGER


Table 3. Recurrences after irradiation

Localization

T-stage

Localization of the primary tumor

Media&turn, lung Mediastinum

I 2

right left

Time to recurrence (months) 17

IO

Salvage treatment

Status of the patient

-l x PEB + I x PEI 3 x PEB + Srg

CR CR

Srg = surgery; PEB = Cisplatinum + Etoposide + Bleomycin. PEI = C&platinum + Etoposide + Ifosfamide.

nausea and vomiting. Some (72.4%) of the patients suffered from Grade I and 2 nausea. Intestinal side effects were observed in 36.2% of the cases. Only 5.2% had Grade 3 toxicity. In contrast to earlier studies ( 1, 2), the long-term side effects observed so far have been negligible. Even though the median time of observation is short as yet, these observations are important, because carboplatinum chemotherapy has recently been proposed as an alternative treatment to irradiation in early-stage testicular seminoma with potentially low late effects ( 15, 26, 3 1) . We did not observe a pelvic or an inguinal lymph node recurrence in our patients. This suggests that the lower field margin at the top of the acetabulum was sufficient. Most of the earlier reports used the lower border of the obturator foramen as a landmark for the inferior field margin. Raising the lower field margin to the top of the acetabulum means that the distance from the field margin to the remaining testicle is increased. Thereby, the amount of scattered irradiation to the healthy testicle is reduced (28). Because the treated patients, who had donated a sperm count prior to radiotherapy, did not donate a second sperm count after the treatment, we are not able to estimate the influence of our treatment technique on the fertility of the patients. The total dose of 30 Gy in Stage IIA and 36 Gy in Stage IIB seems to be sufficient, as no in field recurrences were observed in our patients. A further refinement of out treat-

ment technique could be a reduction of the field size in Stage IIB after the dose of 30 Gy to the involved areas. The dose-response relationship in Stage II testicular seminoma is not clear. However, in most studies doses between 30 and 35 Gy have been applied (see Table I ) with rare in field recurrences. At the moment, we do not see a necessity to lower the radiation dose in Stage IIA/B seminoma, because the side effects have been low in our study and the survival rates of the patients are excellent. Hanks and Coia reported in their analysis of the RTOG patterns of care study, that the acute and long term-side effects of radiotherapy are much lower in patients treated with less than 36 Gy compared to patients who received more than 36 Gy total dose. Below 36 Gy there was no clear doseresponse relationship towards a further reduction of side effects detectable (8 ) . In conclusion, our study is indicating that radiotherapy for Stage II testicular seminoma with lymph node metastasis of less than 5 cm in diameter is a highly efficient treatment with low side effects. In comparison to earlier studies, the recurrent free survival could be increased with modem staging and treatment techniques. The conventional size of the iliacal field could be reduced, by raising the lower field margin from the lower border of the foramen obturatum to the top of the acetabulum, without an increased risk of pelvic or inguinal recurrence.

APPENDIX

List of Participating Centers Ansbach, Aschaffenburg, Berlin Urban Krankenhaus, Berlin Charit& Berlin * Benjamin-Franklin, Darmstadt, Dresden, Duisburg, Dtisseldoti. Erlangen, Freiburg, G6t-

tingen, Hagen, Hamburg-Bundeswehrkrankenhaus, Heidelberg, Karlsruhe St. Vincentius, Karlsruhe Stidtische Klinik, Kgln, Konstanz, Krefeld, Ludwigsburg. Mannheim, Passau, Schwerin, Tiibingen.

REFERENCES

1. Aass. N.; Fossa, S. D.; Host, H. Acute and subacute side effects due to infia-diaphragmatic radiotherapy for testicular cancer: A prospective study. Int J. Radiat. Oncol. Biol. Phys. 22:1057-1064;

1992.

2. Aass,N.; Kaasa, S.; Lund E.; Kaalhus, 0.; Heier, M. S.; Fossa, S. D. Long term somatic side-effectsand morbidity in testicular cancer patients. Br. J. Cancer 61:151-155; 1990. 3. Abdeen, N.; Souhami, L.; Freeman, C.; Yassa, M.; Roman T. Radiation therapy of testicular seminoma: A 15-year survey. Am. J. Clin. Oncol. (CCT) 15:87-90; 1992. 4. Andrews.

C. F.: Micaily,

B.: Brady, L. W. Testicular

semi-

noma. Results of a program of megavolte irradation. Am. J. Clin. Oncol. (CCT) lo:491 -495: 1987. 5. Ball, D.; Barrett, A.; Peckham, M. J. The management of metastatic seminoma testis. Cancer 50:2289-2294: 1982. 6. Casamassima, F.; Ruggiero, C,: CaramelIa, D. er ~1. Hematopoietic bone marrow recovery after radiation therapy: MRI evaluation. Blood 73:1677- 1681; 1989. 7. Clemm. Ch.; Hartenstein, R.; Willich, N. c!r (~1. VinblasineIfosfamide-Cisplatin treatment of bulky seminoma. Cancer 58:2203-2207; 1986. 8. Coia, L. R.: Hanks. G. E. Complications from large field inter-

326

9. 10. 11. 12.

13.

14. 15.

16. 17. 18.

19.

20.

21. 22.

23.

I. J. RadiationOncologyl Biology 0 Physics mediate dose infradiaphragmatic radiation: An analysisof the patternsof careoutcome studiesfor Hodgkin’s diseaseand seminoma. Int. J. Radiat. 0~01. Biol. Phys. 15:29-35; 1988. Dossman, M. A.; Zagars, G. K. Postorchiectomy radiotherapy for stages I and II testicular seminoma. Int. J. Radiat. Oncol. Biol. Phys. 26:381-390; 1993. Duncan, W.; Mtmro, A. J. The management of testicular seminoma: Edinburgh 1970-1981. Br. J. Cancer 55:443448; 1987. Epstein, B. E.; Order, S. E.; Zinreich, E. S. Staging, treatment and results in testicular seminoma. A 12-year report. Cancer 65:405-411; 1990 Fossa, S. D.; Barge, L.; Aass, N.; Johamessen, N. B.; Stenwig, A. E.; Kaalhus, 0. The treatment of advanced metastatic seminoma: Experience in 55 cases.J. Clin. Oncol. 5: 10711077; 1987. Friedman, E. L.; Garnick, M. B.; Stomper, P. C.; Mauch, P. M.; Harrington, D. P.; Richie, J. P. Therapeutic guidelines and results in advanced seminoma. J. Clin. Oncol. 3: 13251332; 1985. Gregory, C.; Peckham, M. J. Results of radiotherapy for stage II testicular seminoma. Radiother. Oncol. 6:285-292; 1986. Horwich, A.; Dearnley, D. P.; A’Hem, A.; Mason, M.; Thomas, G.; Jay, G.; Nicholls, J. The activity of single agent carboplatin in advanced seminoma. Eur. J. Cancer 28A:l307-1310; 1992. Hunter, M.; Peschel, R. E. Testicular seminoma. Cancer 64:1608-1611; 1989. Kellokumpu-Lehtinen, P.; Halme, A. Results of treatment in irradiated testicular seminoma patients. Radiother. Oncol. 18:1-7; 1990. Lai, P. P.; Bernstein, M. J.; Kim, H.; Perez, C. A.; Wasserman, T. H.; Kucik, N. A. Radiation therapy for stage I and IIa testicular seminoma, Int, J. Radiat. Oncol. Biol. Phys. 28:373-379; 1994. Lederman, G. S.; Sheldon, T, A.; Chaffey, J. T.; Herman, T. S.; Gelman, R. S. Coleman, C. N. Cardiac diseaseafter mediastinal irradiation for seminoma. Cancer 60:772-776; 1987. Lederman, G. S.; Herman, T. S.; Jochelson, M.; Silver, B. J.; Chaffey, J. T.; Garnick, M. B.; Richie, J.; Sheldon, T, A.; Coleman, C. N. Radiation therapy of seminoma: 17-year experience at the Joint Center for radiation therapy. Radiother. Oncol. 14:203-208; 1989. Lester, S. G.; Morphis, J. G.; Homback, N. B. Testicular seminoma: Analysis of treatment results and failures. Int. J. Radiat. Oncol. Biol. Phys. 12:353-358; 1986. Loehrer, P. J.; Birch, R.; Williams, S. D.; Greco, F. A.; Einhorn, L. H. Chemotherapy of metastatic seminoma: The southeastern cancer study group experience. J. Clin. Oncol. 5:1212-1220; 1987. von der Masse, H.; Specht, L.; Jacobsen, G. K.; Jakobsen, A.; Madsen, E. L.; Pedersen,M.; Rorth, M.; Schultz, H. Sur-

Volume 39, Number 2, 1997

24. 25.

26.

27. 28.

29.

30. 31. 32. 33. 34. 35.

36.

37. 38.

39.

veillance following orchiectomy for stage I seminoma of the testis. Eur. J. Cancer 29A: 1931- 1934; 1993. Mason, B. R.; Kearsley, J. H. Radiotherapy for stage 2 testicular seminoma: The prognostic influence of tumor bulk. J. Clin. Oncol, 6:1856-1862; 1988. Mirimanoff, R. D.; Sinzig, M.; Kruger, M. et al. Prognosis of human chorionic gonadotropin-producing seminoma treated by postoperative radiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 27:17-23; 1993. Oliver, T.; Edmonds, P. M.; Ong, J. Y. H.; et ul. Pilot studies of 2 and 1 course carboplatin as adjuvant for stage I seminoma: Should it be tested in a randomized trial against radiotherapy? Int. J Radiat. Oncol. Biol. Phys. 29:3-g; 1994. Peckham, M. J.; Horwich, A.; Hendry, W. F. Advanced seminoma: Treatment with cis-platinum-based combination chemotherapy or carboplatin. Br. J. Cancer 52:7-13; 1985. Rassow, J.; Snifter, H. D. Systematische Untersuchungen mit CIF-Thermolumineszenzdetektoren TLD 100 am Aldersen-Phantom zur Gonadenbelastung. Strahlentherapy 139:446-458; 1970. Sagerman, R. H.; Kotlove, D. J. 1.; Regine, W. F.; Chung, C. T.; King, G. A.; Dalal, P. S. Stage II seminoma: Results of postorchiectomy irradiation. Radiology 172:565-568; 1989. Schmidberger, H.; Bamberg, M. Therapieoptionen bei testikularen Seminomen in den frtihen Stadien. Strahlenther. Onkol. 171:125-139; 1995. Schmoll, H. J.; Harstrick, A.; Bokemeyer, C. et uZ. Singleagent Carboplatinum for advanced seminoma. Cancer 72~237-243; 1993. Speer, T. W.; Sombeck, M. D.; Parsons,J. T.; Million, R. R. Testicular seminoma: A failure analysis and literature review. Int. J. Radiat. Oncol. Biol. Phys. 33:89-97; 1995. Thomas, G. M. Stage I, II Seminoma-Then and now. Int. J. Radiat. Oncol. Biol. Phys. 26:545-546; 1993. Thomas, G. M. Controversies in the management of testicular seminoma. Cancer 55:2296-2302; 1985. Thomas, G. M.; Rider, W. D.; Dembo, A. J.; Cummings, B. J.; Gospodarowicz, M.; Hawkins, N. V.; Herman, J. G.; Keen, C. W. Seminoma of the testis: Results of treatment and patterns of failure after radiation therapy. Int. J. Radiat. Oncol. Biol. Phys. 8: 154- 174; 1982. Warde, P.; Gospodarowicz,M. K.; Panzarella T.; Catton, C. N.; Sturgeon,J. F. G.; Moore, M.; Goodman, P.; Jewett, M. A. S. Stage I testicular seminoma: Results of adjuvant irradiation and surveillance.J. Clin. Oncol. 13:2255-2262; 1995. Weissbach, L.; Bussar-Maatz, R. HCG-positive seminoma. Eur. Urol. 23( Suppl. 2):29-30; 1993. Yeoh, E.; Razali, M.; O’Brien, P. C. Radiation therapy for early stage seminoma of the testis. Analysis of survival and gastrointestinal toxicity in patients treated with modem megavoltage technique over 10 years. Austr. Radiol. 37:367-369; 1993. Zagars, G. K. Seminoma with bulky abdominal disease.Int. J. Radiat. Oncol. Biol. Phys. 14:395-397; 1988.