Long-term risk of cardiovascular disease in 5-year survivors of testicular cancer.

PURPOSE: To evaluate the long-term risk of cardiovascular disease (CVD) in survivors of testicular cancer (TC). PATIENTS AND METHODS: We compared CVD incidence in 2,512 5-year survivors of TC, who were treated between 1965 and 1995, with general population rates. Treatment effects on CVD risk were quantified in multivariate Cox regression analysis. RESULTS: After a median follow-up of 18.4 years, 694 cardiovascular events occurred, including 141 acute myocardial infarctions (MIs). The standardized incidence ratio (SIR) for coronary heart disease was 1.17 (95% CI, 1.04 to 1.31), with 14 excess cases per 10,000 person-years. The SIR for MI was significantly increased in nonseminoma survivors with attained ages of less than 45 (SIR = 2.06) and 45 to 54 years (SIR = 1.86) but significantly decreased for survivors with attained ages of 55 years or older (SIR = 0.53). In Cox analysis, mediastinal irradiation was associated with a 3.7-fold (95% CI, 2.2- to 6.2-fold) increased MI risk compared with surgery alone, whereas infradiaphragmatic irradiation was not associated with an increased MI risk. Cisplatin, vinblastine, and bleomycin (PVB) chemotherapy (CT) was associated with a 1.9-fold (95% CI, 1.7- to 2.0-fold) increased MI risk, and bleomycin, etoposide, and cisplatin (BEP) CT was associated with a 1.5-fold (95% CI, 1.0- to 2.2-fold) increased CVD risk and was not associated with increased MI risk (hazard ratio = 1.2; 95% CI, 0.7 to 2.1). Recent smoking was associated with a 2.6-fold (95% CI, 1.8- to 3.9-fold) increased MI risk. CONCLUSION: Nonseminomatous TC survivors experience a moderately increased MI risk at young ages. Physicians should be aware of excess CVD risk associated with mediastinal radiotherapy, PVB CT, and recent smoking. Intervention in modifiable cardiovascular risk factors is especially important in TC survivors. Whether BEP treatment increases CVD risk should be evaluated after more prolonged follow-up.

[Pure dysgerminoma of the ovary. 12 case reports]. / Les dysgerminomes ovariens purs. A propos de 12 cas.

UNLABELLED: Data from the files of 12 patients with pur ovarian dysgerminoma managed between January 1970 and december 1990 were evaluated. Pur ovarian dysgerminoma accounts for 2% of all ovarian malignancies and 28% of malignant germ cell tumors. A palpable pelvic mass was detected in three-fourth of patients. Echography objective ovarian tumor in all cases. Diagnosis was histological. Primary treatment was surgery followed by radiotherapy in 8 cases and chemotherapy in 2 cases. 2 patients developed local recurrences were irradiated and 1 patient developed distant metastases was given chemotherapy in association to radiotherapy. The 5 years survival rate was 91.7%. CONCLUSION: Treatment of ovarian dysgerminoma remains controversial. However, patients with stage la who desire further childbearing can be safely treated with unilateral adnexectomy. For all other patients, radical surgery followed by radiation therapy or chemotherapy for the advanced stages and recurrents dysgerminoma is the treatment of choice. Prospective randomized clinical trials are needed for a well codified therapeutic strategy.

Synergism between radiotherapy and vascular risk factors in the accelerated development of atherosclerosis: a report of three cases.

Radiotherapy is commonly used in the management of testicular tumors. However, to date the risk of radiation-induced vascular occlusive disease in men following radiotherapy for testicular cancer has not been regarded as a major factor in their long-term care. Several animal studies have shown the importance of established vascular risk factors such as hypercholesterolemia and hypertension in the pathogenesis of radiation-induced atherosclerosis. This report presents three cases of premature chronic iliofemoral arterial disease presenting 5,13, and 16 years following exposure to therapeutic irradiation for the treatment of testicular cancer. The patients were in the age group of 40-45 years and all demonstrated associated known atherosclerotic risk factors. The patients had received radiotherapy in the dose of 3,500-4,000 rads in a standard "dog-leg" fashion to the ipsilateral aortoiliac lymphatic chain. Our results showed that young men treated with radiotherapy for testicular cancer may be targeted from the outset for atherosclerotic risk factor reduction to minimize the risk of development of late chronic occlusive arterial disease. It may be that a cohort of men so treated with historical regimes of radiotherapy and now entering middle age should be screened for arterial disease and risk factor reduction.

[Central nervous system. Experience of the Bordeaux University Hospital Center and review of the literature]. / Les dysgerminomes du système nerveux central. Expérience du Centre Hospitalier Universitaire de Bordeaux et analyse de la littérature.

PURPOSE: Retrospective analysis of 17 patients with intracranial germ cell tumors treated in a multidisciplinary consultation at the Bordeaux University Hospital a and literature review. MATERIALS AND METHODS: Seventeen consecutive patients were treated from 1978 to 1995 for a primary intracranial germ cell tumor. Median age was 14 (range 3-29 years). There were two malignant teratoma, six proved germinoma and nine presumed germinoma (diagnostic based on biological, radiological and treatment criteria). All received radiotherapy from 30 to 60 Gy (median 40 Gy) in different volumes. Chemotherapy was administered in 15 cases, three after surgery and 12 after radiotherapy. RESULTS: All tumours were in complete remission after initial treatment. The two malignant teratomas recurred in non-irradiated area after nine and 48 months, and the patients died. None of the germinoma recurred within a follow-up period of two to 17 years (median 65 months). Five and 10 year actuarial overall survival rates were the same: 84% for all histologies and 100% for germinomas. Only two patients developed school difficulties and six presented an hypopituitarism, of which one was consecutive to radiotherapy. Chemotherapy was well tolerated. CONCLUSION: This retrospective study and literature analysis are in favor of limited dose and volume of radiation therapy associated with chemotherapy.

Spontaneous pregnancy after 13 years of amenorrhea in a patient with a voluminous ovarian dysgerminoma and submitted to left adnexectomy and radiotherapy.

The authors illustrate the case of a 17-year-old patient who was submitted to left adnexectomy in view of an ovarian dysgerminoma 24 cm in diameter and weighing 2,800 g. She was subsequently submitted to two cycles of radiotherapy. Following a period of amenorrhea lasting 13 years and characterized by high serum levels of gonadotropins, the patient had a spontaneous pregnancy and at 33 weeks of gestation delivered a live and vital fetus. Therefore the occurrence of post-radiotherapy amenorrhea, characterized by high serum gonadotropin levels, should not always be considered pathognomonic of precocious menopause. The possibility that radiotherapy causes only a temporary alteration in ovarian activity should also be taken into consideration.

Fertility results after ovarian transposition for pelvic malignancies treated by external irradiation or brachytherapy.

The aim of this study was to assess the fertility outcome after ovarian transposition with uterine conservation and pelvic irradiation therapy for pelvic cancer. A total of 37 consecutive cases were reviewed. Of these, 27 patients were treated for a clear cell adenocarcinoma of the vagina and/or the cervix (group 1), nine for an ovarian pure dysgerminoma and one for a para-uterine soft tissue sarcoma (group 2). The pregnancy rate was 15% (4/27) in group 1 and 80% (8/10) in group 2 (P=0.01). A total of 18 pregnancies was observed in 12 patients. Of these, 16 pregnancies were obtained spontaneously and two after in-vitro fertilization. Of the spontaneous pregnancies, 12 (75%) were observed with ovaries still in the abdominal cavity (not repositioned). These results show that the prognosis for fertility is excellent after ovarian transposition and irradiation in patients with morphologically normal genital tracts (group 2). The prognosis is not as good for patients treated for a clear cell adenocarcinoma of the vagina and/or the cervix who may have morphological and/ or functional anomalies of the genital tract, following exposure to diethylstilboestrol and brachytherapy (group 1). Furthermore, these results show that repositioning of the ovary is not essential to achieve pregnancy.

Dysgerminoma of the ovary: a retrospective study.

A retrospective analysis of 22 patients with ovarian dysgerminoma who were treated between 1980 and 1987 was carried out. The median age at presentation was 24.5 years. A total of 15 patients were in stage I, one patient was in stage II and six patients were in stage III. Bilateral ovarian involvement was present in four patients. Conservative surgery was carried out in nine patients and 11 patients underwent radical surgery. Two patients had biopsy only. Fourteen patients received adjuvant radiotherapy and three patients received salvage radiation for recurrent disease. The 10-year actuarial survival rate was 81.8%. All 15 patients in stage I were alive and disease-free at a median follow-up of 125 months. Four patients (one in stage II and three in stage III) died of progressive or recurrent abdominopelvic disease. Pelvic recurrence occurred after conservative surgery in two patients in stage IA who had a tumour size greater than 10 cm, but they were salvaged with radical surgery, chemotherapy and radiotherapy. There were seven patients aged 20 years or less. All were alive and disease-free at a median follow-up of 127 months.

Organ preservation in the treatment of brain tumors.

Within the many histological forms, the preservation of function in the central nervous system has always been predominant. However, the limited or null therapeutic interval for high grade gliomas enables organ preservation in small neoplasms only. In case of favorable histology (e.g. dysgerminoma, low grade small glioma), organ preservation is feasible with adequate techniques. When local control is predominant (e.g. neoplasms of eye) the techniques are long known but applied in very few Centers.

Dysgerminoma: the role of conservative surgery.

Twenty-five cases of pure ovarian dysgerminoma treated at UCLA Medical Center between 1958 and 1992 were reviewed retrospectively. Patterns of recurrence and overall survival were analyzed with regard to primary surgery (conservative versus nonconservative), use of adjuvant therapy, and stage of disease. Fourteen patients (56%) underwent conservative surgical therapy defined as preservation of the contralateral ovary, 10 patients (40%) had nonconservative primary surgery, and one patient (4%) had chemotherapy as primary treatment. Three patients (12%) received adjuvant chemotherapy and nine patients (36%) received postoperative radiation therapy. Fifteen patients (60%) had stage I disease, four (16%) stage II, and three each (12%) had stage III and IV disease. Nine patients (36%) experienced recurrence of disease. Seven of these nine patients (78%) had stage I disease and all seven had undergone conservative primary surgery with preservation of the contralateral ovary. Six of the seven had received no adjuvant therapy. Only one of these seven patients experienced recurrence in the preserved ovary. She was found to have a dysgenetic ovary and an XY karyotype. Three patients with recurrent disease had received radiation therapy after primary surgery. Twenty patients (80%) were alive without disease at follow-up, two patients (8%) were alive with disease, and three (12%) had died of disease. There was no statistically significant difference in recurrence rates between those patients treated with conservative surgery and those treated with nonconservative surgery, although the total number of patients with recurrences was greater in the former group. Our data suggest that a conservative surgical approach is the preferred treatment in patients with pure dysgerminoma of the ovary who desire future fertility. Lack of adjuvant chemotherapy or radiation therapy, rather than type of initial surgery, may be associated with a higher risk of recurrence.

[A case of complete response with radiation and chemotherapy using cisplatin, etoposide and bleomycin].

A 37-year-old man, who had been treated with inguinal orchiectomy and radiotherapy of retroperitoneal and iliac lymph node for r-testicular tumor 6 months earlier, was admitted with a complaint of left leg pain in May 1992. CT scan of pelvic bone revealed osteolytic change of left pubic bone with soft tissue mass. Bone scintigram showed significant uptake of radioisotope on left pubic bone. Biopsy of left pubic bone confirmed histologic findings compatible with that of previous testicular cancer. He was treated with PEB chemotherapy (CDDP, Etoposide and Bleomycin) and radiation therapy. After treatment, the majority of the tumor mass disappeared on CT scan. On repeat biopsy specimens, significant fibrotic change was observed and no cancer cells were recognized. He is alive with no evidence of disease.

Results of a policy of surveillance in stage I testicular seminoma.

PURPOSE: To determine what proportion of patients with Stage I testicular seminoma will be cured with orchidectomy alone. METHODS AND MATERIALS: From August 1984 to December 1991 148 patients with Stage I testicular seminoma were entered on a prospective study of surveillance following orchidectomy. The eligibility criteria included a normal chest X ray, lymphogram, computed tomography (CT) of the abdomen and pelvis, and normal post-orchidectomy tumor markers (AFP and BHCG). Patients were followed with a clinical assessment (markers, chest X ray and CT abdomen and pelvis) at 4 to 6 monthly intervals. RESULTS: With a median follow-up of 47 months (range 7-87 months), the actuarial relapse-free rate was 81% at 5 years. Twenty-three patients have relapsed with a median time to relapse of 15 months (range 2-61 months). Four patients (17%) relapsed at 4 or more years from diagnosis. Twenty-one of the 23 relapses occurred in the paraaortic lymph nodes, one patient relapsed in the mediastinum and ipsilateral inguinal nodes and one patient had an isolated ipsilateral inguinal node relapse. Nineteen patients were treated for relapse with external beam radiation therapy of which three developed a second relapse and were salvaged with chemotherapy. Four patients were treated for first relapse with chemotherapy and one developed a second relapse and died of disease. Age at diagnosis was the only prognostic factor for relapse, with patients age < or = 34 having an actuarial relapse-free rate at 5 years of 70% in contrast to a 91% relapse-free rate in those > 34 years of age. CONCLUSIONS: We recommend that surveillance in Stage I testicular seminoma should only be performed in a study setting until further data regarding the risk of late relapse and the efficacy of salvage chemotherapy is available.

Prognosis of human chorionic gonadotropin-producing seminoma treated by postoperative radiotherapy.

PURPOSE: To clarify the controversy about the management and prognosis of human chorionic gonadotropin-producing seminoma, the records of 132 patients with abnormal human chorionic gonadotropin values treated with radiotherapy were analyzed. METHODS AND MATERIALS: The records of 1169 patients with pure seminoma treated in 10 institutions were screened for serum or urinary human chorionic gonadotropin. One hundred and thirty two patients with elevated human chorionic gonadotropin were found: 96 Stage I, 20 IIA, 7 IIB, 8 III and 1 IV. Median age was 34 y., mean follow-up was 5.0 years [range 1-12 y]. All received infradiaphragmatic radiotherapy (median dose 30 Gy), 25 (2 Stage I, 11 IIA, 5 IIB and 7 III) supradiaphragmatic radiotherapy (median dose: 28.5 Gy) and 10 had also initial chemotherapy (3 Stage IIB 6 III and 1 IV). Patients were allocated to three groups according to human chorionic gonadotropin values: (a) moderate elevation: up to 10 times (104 pts), (b) high elevation: 10 to 100 times (20 pts), (c) very high elevation: over 100 times the upper limit of normal value (8 pts). RESULTS: The proportion of Stage I, II and III was 76%, 19%, 5% in the ME group versus 50%, 35%, 15% in the high elevation group (p < 0.05). In the very high elevation group there were 7 Stage I and 1 Stage IV. Of 132 patients, six died (three dead of disease, two suicides, one acquired immunodeficiency syndrome). The 5 years overall survival probability was 94%. There were seven recurrences (initial stage: 1 Stage I, 2 IIB, 3 III and 1 IV). Of these, there were one in-field recurrence, 3 out of field and 3 in both sites. In 5 of 7, the human chorionic gonadotrophin level was again elevated at recurrence. The 5 years recurrence-free-survival probability was 94% (98% for Stage I, 100% for Stage IIA and 65% for Stage IIB and III [p < 0.001 between I and IIB + III, p < 0.05 between IIA and IIB + III]). Four of the 7 recurrences were salvaged by chimiotherapy +/- radiotherapy. In the high elevation and very high elevation groups, the 5 years recurrence-free-survival was 88%, vs. 96% for the moderate elevation group (p = 0.10). CONCLUSION: Based on this series of patients, human chorionic gonadotropin production is not an unfavorable prognostic factor in pure seminoma. Even in the subgroups with high or very high human chorionic gonadotropin levels (who had a higher proportion of advanced stages), the prognosis remained excellent. In Stage I and IIA seminoma with abnormal human chorionic gonadotropin levels, recurrence rate after post-operative radiotherapy alone is extremely low.

Treatment of stage I testis seminoma by radiotherapy: long-term results--a 30-year experience.

PURPOSE: From 1956 to 1986, we have retrospectively studied 184 patients with a Stage I testis seminoma treated by orchidectomy and radiotherapy at the Institut Gustave Roussy. METHODS AND MATERIALS: The 184 patients received adjuvant radiotherapy to the para-aortic and ipsilateral iliac nodes. Of the 184 patients, 133 received additional mediastinal and supraclavicular irradiation, 47 received supraclavicular without mediastinum irradiation, 98 patients received additional radiotherapy given to inguino-scrotal area. The mean dose of irradiation is 21 Gy which is the lowest dose published. The actuarial survival rate is, respectively, 96%, 93%, 83% and 77% at 5, 10, 15, and 20 years. RESULTS: Four patients relapsed, and four died of progressive disease. Four patients presented cardiovascular disease, all of them had mediastinal irradiation, two were heavy smokers. Seventeen second malignancies were observed, six tumors in the contralateral testis. The actuarial risk of developing a second malignancy is 10% at 10 years, 21% at 20 years. The cure rate and relapse rate in our patients is the same as that obtained by higher dosage of irradiation. CONCLUSION: We conclude that low dose of prophylactic irradiation in lumbo aortic and ipsilateral iliac lymph nodes is active and safe in the treatment of Stage I testis seminoma.

Renal tolerance to nonhomogenous irradiation: comparison of observed effects to predictions of normal tissue complication probability from different biophysical models.

PURPOSE: A patient series was analyzed retrospectively as an example of whole organ kidney irradiation with an inhomogenous dose distribution to test the validity of biophysical models predicting normal tissue tolerance to radiotherapy. METHODS AND MATERIAL: From 1969 to 1984, 142 patients with seminoma were irradiated to the paraaortic region using predominantly rotational techniques which led to variable but partly substantial exposure of the kidneys. Median follow up was 8.2 (2.1-21) years and actuarial 10-year survival (Kaplan-Meier estimate) 82.8%. For all patients 3-dimensional dose distributions were reconstructed and normal tissue complication probabilities for the kidneys were generated from the individual dose volume histograms. To this respect different published biophysical algorithms had been introduced in a 3-dimensional-treatment planning system. RESULTS: In seven patients clinical manifest renal impairment was observed (interval 10-84 months). An excellent agreement between predicted and observed effects was seen for two volume-oriented models, whereas complications were overestimated by an algorithm based on critical element assumptions. CONCLUSIONS: Should these observations be confirmed and extended to different types of organs corresponding algorithms could easily be integrated into 3-dimensional-treatment planning programs and be used for comparing and judging different plans on a more biologically oriented basis.

[Improved prognosis of intracranial germ cell tumors by intensified therapy: results of the MAKEI 89 therapy protocol]. / Verbesserte Prognose intracranialer Keimzelltumoren durch intensivierte Therapie: Ergebnisse des Therapieprotokolls MAKEI 89.

Germ cell tumors of the central nervous system are histological identical to the extracranial tumor sites. According to the localisation germ cell tumors of the CNS are different in symptoms, diagnostic approaches, kind and location of metastases and stratification of therapy. Since 1986 patients with intracranial germ cell tumors are registered in the ongoing study for non-testicular germ cell tumors (MAKEI) of the German Society of Pediatric Oncology and Hematology, and are treated in accordance to therapy guidelines for extracranial sites. In MAKEI 89 therapy strategy was revised with a reduction of radiotherapy and an increased cumulative cisplatinum dose from 200 mg/m2 to 400 mg/m2. Patients with germinoma receive after histologic diagnosis radiotherapy consisting of 30 Gy craniospinal irradiation and 15 Gy tumorboost. Malignant non-germinoma receive after diagnosis by tumor marker in CSF and/or serum 2 courses bleomycin 15 mg/m2 day 1-3, Etoposide 150 mg/m2 day 1 + 2 and cisplatinum 20 mg/m2 days 4-8 (BEP), continued by 2 courses Vinblastine 3 mg/m2 day 1 + 2, Ifosfamide 1500 mg/m2 days 1-5 and cisplatinum 20 mg/m2 days 1-5 (VIP), followed by 30 Gy craniospinal irradiation and 20 Gy tumor boost. In teratoma first line therapy is complete resection. In incomplete resected cases adjuvant chemotherapy according to histological grading is administered. Until 31st January, 1993 101 patients (pts) were registered, containing 69 protocol pts. Diagnosis in protocol pts was teratoma in 8 cases, 2 pts died postnatal because of extended disease, 2/8 pts relapsed, but were salvaged by chemotherapy. 40 pts offered germinomas.(ABSTRACT TRUNCATED AT 250 WORDS)