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Biomedical subjects

A Horwich

Publications and source records attributed to A Horwich.

At least 91 records · Page 5Linked to original sources
PubMed1997

Fertility after chemotherapy for testicular germ cell cancers.

PURPOSE: To analyze the probability of recovery of spermatogenesis after orchidectomy and cisplatin-based chemotherapy (CT) for testicular germ cell cancer. PATIENTS AND METHODS: One hundred seventy-eight patients treated between 1979 and 1991 were selected by the requirement of sperm count both pre-CT and post-CT. Counts were classified as normospermic (NS) if more than 10 x 10(6)/mL, oligospermic (OS) if 1 to 9 x 10(6)/mL, and azoospermic (AS) if less than 1 x 10(6)/mL. The median follow-up time after CT before sperm analysis was 30 months. RESULTS: Analysis of 170 patients whose spermatogenesis was reassessed at least 1 year after CT showed that of 89 patients whose pre-CT counts were NS, the post-CT count was NS in 64%, OS in 16%, and AS in 20%. There was clear evidence for continued recovery beyond 1 year; the probability of spermatogenesis increased to 48% by 2 years and 80% by 5 years. There was a significantly higher probability of recovery to OS and NS count levels in the 54 patients treated with carboplatin-rather than cisplatin-based therapy. There was an independent and similar effect of normal pre-CT count. There was a reduced probability to recover to OS in the 26 patients treated with more than four cycles of CT. A prognostic model identified three groups with 25%, 45%, and 82% probabilities of recovering spermatogenesis by 2 years after CT. CONCLUSION: Analysis of pre-CT sperm count together with details of planned treatment can be used to predict recovery of spermatogenesis following germ cell CT.

Adolescent↗
PubMed1997

Randomized trial of bleomycin, etoposide, and cisplatin compared with bleomycin, etoposide, and carboplatin in good-prognosis metastatic nonseminomatous germ cell cancer: a Multiinstitutional Medical Research Council/European Organization for Research and Treatment of Cancer Trial.

PURPOSE: This prospective randomized multicenter trial was designed to evaluate the efficacy of carboplatin plus etoposide and bleomycin (CEB) versus cisplatin plus etoposide and bleomycin (BEP) in first-line chemotherapy of patients with good-risk nonseminomatous germ cell tumors. PATIENTS AND METHODS: Between September 1989 and May 1993, a total of 598 patients with good-risk nonseminomatous germ cell tumors were randomized to receive four cycles of either BEP or CEB. In each cycle, the etoposide dose was 120 mg/m2 on days 1, 2, and 3, and the bleomycin dose was 30 U on day 2. BEP patients received cisplatin at 20 mg/m2/d on days 1 to 5 or 50 mg/m2 on days 1 and 2. For CEB patients, the carboplatin dose was calculated from the glomerular filtration rate to achieve a serum concentration x time of 5 mg/mL x minutes. Chemotherapy was recycled at 21-day intervals to a total of four cycles. RESULTS: Of patients assessable for response, 253 of 268 (94.4%) of those allocated to receive BEP achieved a complete response, compared with 227 of 260 (87.3%) allocated to receive CEB (P = .009). There were 30 treatment failures in the 300 patients allocated to BEP and 79 in the 298 allocated to CEB (log-rank chi 2 = 26.9; P < .001), which led to failure-free rates at 1 year of 91% (95% confidence interval [CI], 88% to 94%) and 77% (95% CI, 72% to 82%), respectively. There were 10 deaths in patients allocated to BEP and 27 in patients allocated to CEB (log-rank chi 2 = 8.77; P = .003), which led to 3-year survival rates of 97% (95% CI, 95% to 99%) and 90% (95% CI, 86% to 94%), respectively. CONCLUSION: With these drug doses and schedules, combination chemotherapy based on carboplatin was inferior to that based on cisplatin. This BEP regimen that contains moderate doses of etoposide and bleomycin is effective in the treatment of patients with good-prognosis metastatic nonseminoma.

Adult↗
PubMed1996

Spermatocytic seminoma: a clinicopathological review of ten patients.

Spermatocytic seminoma is an uncommon variety of testicular neoplasm, differing from its classical counterpart at both clinical and pathological levels and having a low propensity to metastasize. This is a retrospective review of ten patients with pathologically confirmed and reviewed disease who were seen at the Royal Marsden Hospital. All patients presented as Stage I. Five were treated with radiotherapy and five have undergone surveillance. The median age was 56.5 years. The median follow-up is 8 years and no patient has relapsed. Two have died of intercurrent disease. Our series supports others of a similar size in the literature with respect to both the rarity and the good prognosis of spermatocytic seminoma. With only one case of relapse confirmed in the literature, this is a subgroup of patients in whom radiotherapy can safely be omitted.

Combined Modality Therapy↗
PubMed1996

An analysis of surveillance for stage I combined teratoma--seminoma of the testis.

We analysed 973 patients with stage I testicular tumours presenting between 1983 and 1994. The median ages at presentation for non-seminomatous germ cell tumour (teratoma) were 27 years, seminoma 36 years and combined tumour 33 years. These differences were statistically significant (Mann-Whitney P < 0.05), suggesting that combined tumours may have a separate natural history. We, therefore, analysed all stage I patients managed with surveillance (530 in total) post orchidectomy. The actuarial 5 year relapse-free survival and anatomical patterns of relapse were identical for non-seminomatous germ cell tumour (NSGCT) and combined tumour and both were statistically distinct from seminoma (P = 0.01, log-rank test, chi-square test P = 0.001). The association of seminoma within a histologically confirmed NSGCT has no influence on the clinical outcome.

Adult↗
PubMed1996

Primary chemotherapy: how does it compare with surgery?

Small-volume metastatic nonseminoma primary chemotherapy following orchidectomy cures the same high proportion of patients as does retroperitoneal lymph node dissection (RPLND). The 5-year survival in 122 patients treated at the Royal Marsden Hospital was 97%; 35 of these men had postchemotherapy lymphadenectomy and only 5 suffered loss of ejaculation. Primary chemotherapy is a reasonable alternative to RPLND for stage II testicular nonseminoma.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

Imaging metastatic testicular germ cell tumours with 18FDG positron emission tomography: prospects for detection and management.

The aim of this study was to investigate the role of positron emission tomography (PET) with [18F]fluoro-2-deoxyglucose (18FDG) in metastatic testicular germ cell tumours. Twenty-one patients with stage II-IV testicular germ cell tumours were imaged by PET with a multiwire proportional chamber PET system and 18FDG. Avid 18FDG uptake was seen in metastatic disease from primary seminoma and malignant teratoma. Normal tissue uptake was seen in differentiated teratoma or necrotic, fibrotic tissue. 18FDG standard uptake values and tumour to normal tissue ratios were 6.0 +/- 1.4 and 1.7 +/- 0.4 (mean +/- 1SD), respectively, for malignant tissue. Reduction of 18FDG tumour to normal tissue ratios from pre-treatment to on-treatment scans was predictive of response (n = 3). No significant reduction in 18FDG uptake was seen in patients not responding to therapy (n = 2). These results suggest a role for 18FDG PET in the detection and management of metastatic testicular germ cell tumours.

Abdominal Neoplasms↗
PubMed1995

Radiotherapy results in early stage low grade nodal non-Hodgkin's lymphoma.

This is a retrospective review of stages I and II low grade nodal non-Hodgkin's lymphoma (NHL) seen at the Royal Marsden Hospital and treated with radiotherapy alone. From January 1970 to December 1989, 58 patients were treated. The Ann Arbor staging system was modified to subdivide stage II into localised and extensive disease, with localised disease representing no more than two contiguous regions. There were 40 stage I patients and 18 stage II patients (eight localised and 10 extensive). Volume of the radiotherapy was involved field only in 30 patients and extended fields in 28 patients. The median dose was 40 Gy in 20 fractions. The pattern of relapse was assessed as being systemic or within the standard volume. Survival and progression-free survival (PFS) were calculated. Prognostic variables of age, histology, stage and radiotherapy volume were analysed by multivariate analysis. The 5- and 10-year PFS for the total group were 59 and 43%, and corresponding OS figures were 93 and 79%. Age less than 60 years was a predictor of improved survival but not for PFS and we found no significance in histology, stage or extent of radiotherapy field for the other variables. All relapses occurred with disease outside the original volume, with three patients also relapsing in-field. Treatment of this disease produced an OS at 10 years of 79%. The plateau on the PFS plot suggested that some patients are cured. Young age was the only prognostic factor found for survival. Relapse is most frequently outside the treated volume. Our current treatment policy for stage I and II low grade NHL is involved field radiotherapy to a dose of 35 Gy in 20 fraction over 4 weeks.

Adult↗
PubMed1995

High-dose carboplatin and etoposide for salvage chemotherapy of germ cell tumours.

We evaluated high-dose carboplatin and etoposide with autologous bone marrow stem cell support in the salvage treatment of patients with metastatic germ cell tumours who had failed previous chemotherapy. The treatment programme comprised initial conventional dose chemotherapy. 23 patients received a first cycle of high-dose treatment, and 12 who showed no evidence of progression had a second cycle 2-3 months later. 8 of the 23 patients treated with high-dose chemotherapy are alive in remission 4-29 months from the start of high-dose treatment. 3 of these 8 required further treatment for recurrence. In the initial part of the study, the dose of carboplatin was escalated in successive patients. Grade 3/4 treatment-related toxicity occurred in 4 of 18 patients (1 fatal) who received carboplatin doses to give a AUC (area under the serum concentration/time curve) of 30 mg.min/ml or less and 3 of 5 patients (2 fatal) who received higher doses. We, therefore, recommend 30 mg.min/ml for further evaluation in chemotherapy sensitive patients.

Adolescent↗
PubMed1995

Programmed cell death in response to chemotherapeutic agents in human germ cell tumour lines.

Testicular germ cell tumours are amongst the most chemosensitive neoplasms both in vivo and in vitro. In the present study we demonstrate that following exposure to drugs used in chemotherapeutic treatment of testicular germ cell cancer tumour cells undergo death by apoptosis. Thus, after exposure of the GCT27 embryonal carcinoma cell line to cisplatin, we observed the degradation of DNA into oligonucleosomal fragments, which is a hallmark of apoptosis. Furthermore, light, fluorescence and electron microscopy reveal the presence of condensed abnormal shaped nuclear chromatin which is characteristic of apoptosis. Changes diagnostic of apoptosis were also observed following (a) cisplatin treatment of the GCT48 and Susa embryonal carcinoma cell lines and the GCT44 yolk sac tumour cell line and (b) etoposide treatment of the GCT27 and Susa cell lines. When the GCT27 cell line was treated with 15 microns cisplatin, apoptosis was first observed at 6-9 h and greater than 90% of cells were dead within 24 h. Apoptosis was not blocked when cisplatin-treated cells were incubated in the presence of cycloheximide, although this agent did cause a 4-6 h delay in the onset of cell death. In addition, we demonstrated that the GCT27 cell line can be induced to undergo apoptosis by exposure to low concentrations of the calcium ionophore, ionomycin. These observations show that germ cell tumours are remarkably sensitive to a range of agents that act by different mechanisms. They are triggered to undergo apoptosis rapidly by a mechanism that is not blocked by inhibitors of protein synthesis.

Apoptosis↗
PubMed1995

Microsatellite instability in human testicular germ cell tumours.

DNA samples obtained from 29 testicular germ cell tumours have been screened for instability at nine different microsatellite sequences consisting of dinucleotide, trinucleotide and tetranucleotide loci. Overall, in tumours from six (21%) patients we found abnormalities in at least one of the loci examined. Mutation was most frequently found in tetranucleotide and trinucleotide repeats with only a low proportion of alterations in dinucleotide repeats. This pattern of instability is distinct from that reported in colorectal cancer and other cancers that have a high level of alterations in dinucleotide repeats.

Adult↗
PubMed1995

Prognostic significance of early serum tumor marker half-life in metastatic testicular teratoma.

PURPOSE: To determine whether the initial regression rates of serum tumor marker concentration (alpha-fetoprotein [AFP] and beta-human chorionic gonadotrophin [HCG]) were important prognostic factors after chemotherapy for germ cell tumors. PATIENTS AND METHODS: The analysis was confined to patients with at least two precise marker assay results between days 7 and 22 from start of platinum-based combination chemotherapy, with at least 7 days between markers. One hundred eighty-three patients were eligible and marker half-life (MHL) was evaluated for AFP in 142 and for HCG in 111 cases. MHL was calculated from the following formula: MHL = Ln1/2/G, where G was the gradient of the marker slope on a plot of Ln marker concentration versus time. MHL was regarded as prolonged if more than 3 days for HCG or more than 7 days for AFP. RESULTS: The median AFP MHL was 6 days (range, 2.7 to 237) and the median HCG MHL was 2.6 days (range, 1.7 to 37.5). Forty-nine of 142 patients (35%) had a prolonged AFP MHL; 39 of 111 patients (35%) had a prolonged HCG-MHL. A prolonged MHL did not identify relapse after front-line chemotherapy. The positive predictive value of MHL tests in identifying patients who progressed after front-line therapy was 18% for HCG, 20% for AFP, and 18% for either marker. A prolonged MHL did indicate a higher risk of mortality (hazards ratio [HR], 2.4; P = .016), but again the positive predictive value of this test was only 23%. CONCLUSION: Early evaluation of MHL by this method does not predict patients at higher risk of progression after front-line chemotherapy, and also is a poor guide to long-term prognosis.

Adolescent↗
PubMed1995

Evaluation of the efficacy of the VEEP regimen in adult Hodgkin's disease with assessment of gonadal and cardiac toxicity.

PURPOSE: The aim of this phase II study was to investigate the potential of the vincristine, epirubicin, etoposide, and prednisolone (VEEP) regimen to reduce the risks of long-term sequelae of chemotherapy such as sterility, cardiopulmonary damage, and second malignancies, while maintaining efficacy in terms of response and survival. PATIENTS AND METHODS: Eighty-five adult patients with newly diagnosed and previously untreated stage II to IV Hodgkin's disease (HD) were entered and monitored for a minimum of 1 year. Patients were treated to maximum response plus two further courses, and if they had not attained a complete response (CR) or CR-unconfirmed/uncertain [CR(u)] were changed to second-line chemotherapy. Adjuvant radiotherapy was administered to patients with bulky disease and those with postchemotherapy residual masses. Measurements of left ventricular ejection fraction (LVEF), gonadotropins in females, and sperm count in males were taken both before and after treatment with VEEP. RESULTS: The maximum rates of response were as follows: CR, 32%; CR(u), 47%; and PR, 21% [CR + CR(u), 79%]. The median follow-up duration is 45 months, with a 5-year overall survival (OS) rate of 89% and failure-free survival (FFS) rate of 62%. Patients in CR at the end of chemotherapy had a higher FFS at 5 years compared with patients in CR(u) (88% v 56%). Acute toxicity was mild, with no pulmonary toxicity or treatment-related deaths. The median LVEF was 62% before VEEP and 57% after VEEP. Gonadal function tests following treatment were normal in 92% of males and 100% of females. No second malignancies have been observed. CONCLUSION: VEEP is an active combination with tolerable acute toxicity that preserves fertility and cardiopulmonary function. The efficacy of VEEP is comparable to that of established regimens, but a definitive evaluation of its potential to reduce second malignancies will require a longer follow-up duration.

Adolescent↗
PubMed1994

Salvage of relapse of patients with Hodgkin's disease in clinical stages I or II who were staged with laparotomy and initially treated with radiotherapy alone. A report from the international database on Hodgkin's disease.

PURPOSE: To analyze presentation variables that might indicate a high or low likelihood of success of the treatment of patients relapsing after initial radiotherapy of Hodgkin's disease in clinical Stages I or II who were staged with laparotomy. METHODS AND MATERIALS: Data were analyzed on 681 patients in the International Database on Hodgkin's Disease who were initially in clinical Stages I or II, who were staged with laparotomy, and who relapsed after initial treatment with irradiation alone. Factors analyzed for outcome after first relapse included initial stage, age, sex, histology, presentation (supra- vs. infradiaphragmatic), number of involved areas, mediastinal involvement, E-lesions, B-symptoms, erythrocyte sedimentation rate, lactate dehydrogenase, alkaline phosphatase, serum albumin, and hemoglobin. RESULTS: Only age and histology showed significant prognostic impact in univariate and multivariate analyses. The influence of age may perhaps be attributed to suboptimal treatment of some older patients. Patients with nodal relapse had a better prognosis than patients with extranodal relapse, probably indicating that the latter had more extensive disease at relapse. The length of the initial disease-free interval had no influence on prognosis after relapse. CONCLUSION: The decisive factors for outcome after initial treatment with irradiation alone are a) the factors predicting the risk of relapse after initial radiotherapy and b) the factors predicting outcome after relapse, that is, histologic subtype and extent of disease at relapse.

Adult↗