S. Culine

The growing teratoma syndrome: results of therapy and long-term follow-up of 33 patients

Growing teratoma syndrome (GTS) is defined as an increase in tumour size during or after chemotherapy for germ cell tumour (GCT), and only mature teratoma at histological analysis of the resected tumour specimen. Between 1985 and 1997, 30 male patients fulfilling GTS criteria were included in the present study. 3 female patients were also included but analysed separately. A mature teratoma component was found in 86% of the primary GCT. 3 male patients (10%) had a complication at diagnosis of GTS. One male patient (4%) having undergone complete resection (n=24) had a recurrent GTS, compared with all but 1 patient (83%) in whom resection was partial (n=6) (P<0.001). 2 (8%) and 3 (50%) male patients treated with complete and partial resection subsequently developed a malignant NSGCT respectively (P=0.01). 2 female patients treated with partial resection presented a recurrent GTS. One of them died of this recurrent GTS. GTS is an entity in its own right with respect to complications and the natural history of the disease. Complete surgical resection is the treatment of choice for GTS.

Primary mediastinal nonseminomatous germ cell tumors: results of modern therapy including cisplatin-based chemotherapy.

PURPOSEnPrimary mediastinal nonseminomatous germ cell tumors (NSGCT) are uncommon neoplasms and clinically and biologically distinct from other germ cell tumors (GCT). We describe the clinical and biologic features of these patients and evaluate the results of treatment during the cisplatin era.nnnPATIENTS AND METHODSnBetween 1976 and 1993, 38 patients with mediastinal NSGCT received cisplatin-based chemotherapy as part of their primary treatment. Twenty-nine of them were initially treated at the Institut Gustave-Roussy (IGR), VillejuiF, France, and nine were referred for salvage treatment.nnnRESULTSnOf the 29 patients initially treated at IGR, 11 (39%) had metastasis. A complete response (CR) to therapy was obtained in 19 of 29 patients (66%) after chemotherapy and surgery. Ten patients (34.5%) have remained free of disease with a median follow-up of 89 months. All patients who did not achieve a CR died of disease. The 2-year overall survival rate for the IGR patients is 45% and the 2-year disease-free survival is 37%. Only the presence of extrapulmonary metastasis was of prognostic significance in the univariate analysis (P = .0095). None of the 20 patients who required salvage therapy is currently disease-free. Five patients developed and subsequently died of a hematologic malignancy at an interval range of 1 to 47 months from treatment of mediastinal NSGCT. Cytogenetic analysis of leukemic cells found an isochromosome of the short arm of chromosome 12 (12p) in two cases. The incidence of leukemia was 21% in patients who attained a CR.nnnCONCLUSIONnPrimary mediastinal NSGCT is a clinical and biologic entity that should be distinguished from other GCT. About 40% of these patients can envisage long-term survival with modern therapy that includes cisplatin-based chemotherapy followed by surgical resection of residual masses. New strategies are required for patients who do not attain a CR. Predictive factors and improvement in therapy are required for mediastinal NSGCT-associated leukemia.

Doxorubicin and ifosfamide in patients with metastatic sarcomatoid renal cell carcinoma: A phase II study of the genitourinary group of the French federation of cancer centers

PURPOSEnWe assessed the efficacy and toxicity of a chemotherapy regimen combining doxorubicin and ifosfamide in patients with metastatic sarcomatoid renal cell carcinoma.nnnMATERIALS AND METHODSnOf the 25 patients included in a prospective multicenter phase II trial 23 were evaluable for efficacy and toxicity studies after pathological review.nnnRESULTSnA median of 3 cycles per patient (range 1 to 8) was administered. No objective response was observed. Median time to progression was 2.2 months and median overall survival was 3.9 months. A single patient died of toxicity.nnnCONCLUSIONSnThe results do not support the standard use of doxorubicin/ifosfamide chemotherapy in patients with metastatic sarcomatoid renal cell carcinoma.

Stage I non-seminomatous germ-cell tumours of the testis: identification of a subgroup of patients with a very low risk of relapse

There is no consensus about a reproducible prognostic model capable of distinguishing between clinical stage I non-seminomatous germ cell tumour (NSGCT) carrying a high and low risk of relapse. The aim of this study was to assess the prognostic value of histological parameters in patients with stage I NSGCT undergoing surveillance after orchiectomy. We retrospectively evaluated tumour specimens from 88 consecutive stage I NSGCT patients undergoing surveillance in our institution between 1984 and 1996. 24 patients relapsed (27%). Multivariate analysis singled out vessel invasion (VI) (relative risk (RR)=3.8; 95% confidence interval (CI) 1.4-10.4) and the presence of mature teratoma (RR= 0.2; 95% CI 0.1-0.6) as independently correlated with relapse-free survival (RFS). Patients can be classified accordingly into three prognostic groups with a low (27 patients with mature teratoma but without VI), intermediate (34 patients with both VI and mature teratoma or with neither VI or mature teratoma) and a high risk (23 patients with VI, but without mature teratoma) of relapse. Relapse rates in these three groups were 0%, 29% (95% CI: 23-35%) and 61% (95% CI: 55-67%), respectively. This prognostic index, based on two standard pathological parameters, identified a subgroup with a very low risk of relapse that represents approximately one third of stage I patients. Patients who belong to this subgroup should be managed by surveillance only, instead of retroperitoneal lymph node dissection (RPLND) or adjuvant chemotherapy.

Penile cancer chemotherapy: Twelve years' experience at Institut Gustave-Roussy

Between 1980 and 1992, 14 patients (median age 50 years) with penile carcinoma were treated with multidrug combination chemotherapy in our institution. Twelve patients had Stage IV (Jackson classification) tumor, 1 patient each had Stage III and Stage II. All patients received cisplatin-based chemotherapy. Cisplatin was associated with either 5-fluorouracil (4 patients), methotrexate and bleomycin (4 patients), methotrexate (3 patients), Adriamycin (1 patient), bleomycin and vinblastine (1 patient), or bleomycin and epirubicin (1 patient). Thirteen patients were evaluable for response. Objective response was encountered in 2 patients (15%) with 1 complete response and 1 partial response. Response duration was difficult to determine because of additive radio-therapy or patient was lost to follow-up. There were 2 patients with long-term evidence of no disease among 12 patients with Stage IV disease. These 2 patients received complementary irradiation in association with the chemotherapy. The response rate was dismal in our series. Methotrexate-based regimens seem to be the most active. The bimodality treatment with multidrug chemotherapy and radiotherapy for advanced penile cancer could offer a survival advantage in the management of these patients.

Adult Wilms' tumour: Review of 22 cases

The Institut Gustave Roussy experience with nephroblastoma in 22 patients older than 16 years during a 19-year period (1973-1992) was retrospectively reviewed. All patients underwent a nephrectomy. There were 4 stage I, 8 stage II, 3 stage III and 7 stage IV patients. Initial postnephrectomy therapy included single modality approach in 7 patients (radiotherapy in 1 and chemotherapy in 6) and combined modality approach (radiotherapy and chemotherapy) in 15 patients. The agents used most often were actinomycin, vincristine and doxorubicin. 2 of 7 (29%) and 7/15 (47%) patients are disease-free survivors after first-line treatment. Salvage chemotherapy was given in 13 patients. Only 1 patient experienced a subsequent sustained complete remission. After a mean follow-up of 100 months (range 10-240), 12/22 patients (55%) are alive, including 10 who are disease-free (45%). We confirm that adult patients are likely to have more advanced disease and poorer prognosis than children. The combined modality approach is more active than one-modality therapy. Aggressive treatment, including the three-drug regimen actinomycin+vincristine+doxorubicin, regardless of stage, associated to irradiation starting from stage II, is recommended.

Phase II study of all-trans retinoic acid administered intermittently for hormone refractory prostate cancer

PURPOSEnWe assess the efficacy and toxicity of all-trans retinoic acid administered intermittently for hormone refractory prostate cancer.nnnMATERIALS AND METHODSnA total of 26 patients with histologically confirmed adenocarcinoma of the prostate and manifestations of progressive metastatic disease, despite at least 1 hormonal therapy, were included in the study. Patients received a single oral dose of 45 mg./m.2 all-trans retinoic acid daily for 7 days followed by 7 days of no treatment, and then resumed treatment on day 14. This schedule was continued until progression or limiting toxicity occurred. Response was assessed based on serial measurements of serum prostate specific antigen and pain scores every other week. In addition, objective responses were evaluated every 12 weeks in patients with bi-dimensionally measurable metastases.nnnRESULTSnAll-trans retinoic acid was administered for 168 weeks (median 6 weeks per patient, range 2 to 21). Toxicity was mild. No patient stopped therapy because of toxicity. Of the patients 4 (15%) demonstrated a biological response of 50% or greater serum prostate specific antigen decrease. No objective response was observed among 11 patients with measurable metastases. Of 17 patients who required analgesics at the onset of all-trans retinoic acid treatment only 1 achieved a significant reduction of pain. Median survival time from the onset of all-trans retinoic acid treatment was 19 months (range 2 to 24).nnnCONCLUSIONSnAll-trans retinoic acid has minimal activity in hormone refractory prostate cancer.

Primary Chemotherapy in Patients with Nonseminomatous Germ Cell Tumors of the Testis and Biological Disease Only After Orchiectomy

PURPOSEnWe assessed the efficacy of primary chemotherapy in patients with nonseminomatous germ cell tumors of the testis and elevated serum tumor markers as the only evidence of disease after orchiectomy.nnnMATERIALS AND METHODSnWe analyzed the outcome of 20 patients with biological disease only who received cisplatin-based (16) or carboplatin-based (4) chemotherapy as primary treatment following orchiectomy.nnnRESULTSnSerum tumor markers returned to normal levels in all 20 patients. One patient required subsequent surgery for recurrent retroperitoneal mature teratoma. Two patients experienced a relapse with active disease, 1 of whom died of progressive germ cell tumor. Of the patients 19 remained free of disease 18 to 116 months after the end of treatment.nnnCONCLUSIONSnSince results with primary retroperitoneal lymph node dissection suggest that elevated serum tumor markers usually reflect systemic metastases rather than retroperitoneal disease, primary chemotherapy seems to be the most appropriate strategy to consider in patients with biological disease only following orchiectomy.

Initial management of primary mediastinal seminoma: radiotherapy or cisplatin-based chemotherapy?

Primary mediastinal seminoma is an uncommon neoplasm, the optimal management of which is still debated. Radiotherapy produces a 65% disease-free survival rate. We assess whether these results have been improved with the advent of cisplatin-based chemotherapy. Data from 14 patients treated at the Institut Gustave-Roussy were reviewed. 9 had received cisplatin-based chemotherapy (Group 1): their outcome was compared with that of 5 patients treated with radiotherapy without chemotherapy (Group 2). We also reviewed data from the English literature using strict criteria, and report results concerning patients who received cisplatin-based chemotherapy and those who received radiotherapy. 8 of the 9 patients (89%) in Group 1 are long-term disease-free survivors and only 3 of 5 patients in Group 2. The patient who died in Group 1 was the only one who refused surgical resection of residual masses after chemotherapy. The review of the literature revealed that 59 of 68 (87%) patients initially managed with cisplatin- or carboplatin-based chemotherapy and for whom sufficient data are available, are long-term survivors and free of disease. Some of these patients had also received radiotherapy. Only 64 of 103 (62%) treated with thoracic radiotherapy without chemotherapy were long-term disease-free survivors. The disease-free survival rate of 51 patients who received cisplatin-based chemotherapy (excluding those who received carboplatin) was 86%. The difference in survival between patients administered cisplatin-based chemotherapy and those who underwent radiotherapy is apparently not due to unbalanced prognostic factors, the effect of time or non-specific medical management. We conclude that cisplatin-based chemotherapy allows long-term disease-free survival in approximately 85% of patients. These results seem to be higher than those obtained without cisplatin-based chemotherapy. However, a randomised study is required for definitive conclusions, but it is very unlikely that such a study will be performed due to the rarity of this neoplasm. Another alternative would be a meta-analysis based on individual data.

Metachronous gonadal and extragonadal primaries, or late relapse of germ cell tumor?

We report five distinct cases of apparently metachronous extragonadal and gonadal germ cell tumors (GCT) occurring in the same patient. Two patients had metachronous GCT of the central nervous system and the testis. One of these patients had been successfully treated for a germinoma of the pineal gland and developed a nonseminomatous GCT of the testis 10 years later. The second patient had a primary seminoma of the testis treated by orchiectomy followed by radiotherapy and developed a germinoma of the sphenoidal sinus 17 months later. Three other patients had an apparently metachronous retroperitoneal and testicular GCT with 22, 44, and 66 months elapsing, respectively, between the first and second neoplasms. These cases suggest that the remaining testis is not only at risk for a second primary GCT, but that a second GCT may emerge at an extragonadal site. A genetic predisposition may account for some of these cases and the occurrence of bilateral testicular GCT. In none of these cases, however, could we ascertain whether testicular GCT was truly a second primary or a relapse of a primary retroperitoneal GCT in our cases.