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A Horwich

Publications and source records attributed to A Horwich.

At least 127 records · Page 7Linked to original sources

Risk factors for carcinoma in situ of the contralateral testis in patients with testicular cancer. An interim report.

In a study aimed at evaluating risk factors for carcinoma in situ (CIS) in the contralateral testis of selected patients with testicular cancer, information from 89 patients who have had contralateral testicular biopsies is available. The biopsies were performed because of the coexistence of the previously established risk factors - atrophy of the remaining testis, or a history of maldescent. CIS was diagnosed in 13% of patients, the prevalence being the same for both open and needle biopsies. Compared to its overall prevalence in the contralateral testis in testicular cancer an increased risk of CIS has been found in clinically atrophic testes but has not been found for maldescent. Patients found to have CIS were younger than those in whom it was not detected.

Adult↗

Ejaculatory dysfunction after retroperitoneal lymphadenectomy.

The effects of retroperitoneal lymphadenectomy on ejaculation have been examined in 186 patients who had removal of residual masses after chemotherapy for metastatic non-seminomatous germ cell tumours. The results were analysed for significance using a chi 2 test of independence. Forty-one men (22%) permanently lost ejaculation postoperatively. The larger the size of the mass removed, the more likely the patient was to have ejaculatory failure (< 4 cm = 4%, 4-8 cm = 17%, > 8 cm = 58%; p < 0.005). Removal of bilateral masses was more likely to result in loss of ejaculation than unilateral masses (45 and 12%, respectively, p < 0.005). There has been significantly less postoperative ejaculatory dysfunction since 1984 when a nerve sparing dissection was introduced (before 1984 36%, since 1984 16%, p < 0.005). The incidence of ejaculatory dysfunction following retroperitoneal lymphadenectomy is therefore determined by the size and position of residual lymph node masses after chemotherapy and can be kept to a minimum by a careful nerve sparing operative technique.

Data Interpretation, Statistical↗

Increasing the dose intensity of chemotherapy in poor-prognosis metastatic non-seminoma.

The overall cure rate of patients with metastatic non-seminoma of the testis is high and a recent survey of 795 patients by the Medical Research Council indicated that 85% were alive 3 years after the start of chemotherapy. Two major categories of patients can be identified with a poorer prognosis. First are those with adverse prognostic factors at presentation defined by presence of one of the following factors: high tumour markers, more than 20 lung metastases, liver bone or brain metastases, mediastinal mass more than 5 cm. In these patients, the RMH is investigating accelerated chemotherapy employing a 7 day cycle, combined carboplatin and cisplatin and infusional bleomycin (C-BOP regimen). Of 21 patients followed for a median of 18 months, 18 (85%) have remained continuously disease free. The second adverse group are patients who have already failed first line chemotherapy. A multivariate prognostic factor analysis on 105 patients treated at the Royal Marsden Hospital indicates that adverse factors for salvage chemotherapy are the disease-free interval and the extent of disease at relapse. Our approach to patients with disseminated relapse includes high dose carboplatin and etoposide with autologous bone marrow support. With follow-up from 3-24 months, 7 of 11 patients treated with high dose chemotherapy remain continuously free from progressive disease. The need for an alkylating agent in the high dose combination is questionable.

Analysis of Variance↗

Chemotherapy of seminoma.

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Antineoplastic Combined Chemotherapy Protocols↗

Radiotherapy update.

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Combined Modality Therapy↗

Does extragonadal presentation impart a worse prognosis to abdominal germ-cell tumours?

The prognostic significance of extragonadal rather than gonadal presentation of germ-cell tumour in 51 patients presenting between 1979 and 1988 with abdominal tumours was compared with that of 51 control patients with testicular primary tumours matched for bulk fo disease, serum tumour marker concentration, age and year of treatment. Very large volume tumour was found at initial staging in 24 extra-gonadal cases (47%) and high tumour markers in 29 (57%). Actuarial survival at 2 and 5 years was 82% and 70% for cases and 78% and 63%, respectively, for controls. These outcomes were not significantly different and the relative hazard of death for cases compared with controls was 0.7 (95% confidence intervals 0.3-1.5). Thus the presentation of germ-cell tumours with a retroperitoneal mass does not itself adversely influence prognosis compared with testicular presentation with equivalent disease extent. However it is rare for extragonadal presentation to be associated with small volume disease.

Abdominal Neoplasms↗

The activity of single-agent carboplatin in advanced seminoma.

Between 1982 and 1990, 70 patients with advanced metastatic seminoma were treated with 4-6 courses of single-agent carboplatin (SAC) administered at 400 mg/m2 every 3-4 weeks. Treatment was of low toxicity and no patients suffered neurotoxicity, ototoxicity or significant renal damage. There was only one episode of neutropenic sepsis and no thrombocytopenic bleeding. The median follow-up of surviving patients was 3 years. 16 patients have relapsed and 4 of these 16 have died, thus the actuarial 3-year relapse-free survival was 77% (95% CI 65-86%), cause-specific survival was 94% (95% CI 82-99%) and overall survival was 91% (95% CI 80-96%). The risk of relapse was reduced by post-chemotherapy irradiation (PCRT) to involved nodes, occurring in 1/20 patients treated with PCRT compared with 11/31 who could have been treated but were not (P = 0.04). Of the 16 patients who relapsed, 12(75%) have been salvaged with combination chemotherapy and remain free from further relapse with a median follow-up of 18 months. Though this level of survival is equivalent to that obtained with initial cisplatin-based combination chemotherapy, the recurrence rate indicates that SAC remains an investigative treatment, except for unfit patients.

Adult↗

The association of germ cell tumours of the testis with sarcoid-like processes.

Sarcoid-type pulmonary lymphadenopathy associated with testicular cancer is a rare condition which has been previously reported in only 14 cases. Earlier case reports have failed to distinguish between generalized sarcoidosis as opposed to a local granulomatous reaction to tumour. We describe a further 8 cases of the association and provide strong supportive evidence for systemic sarcoidosis in 5 of our patients. In 3 of our patients with systemic sarcoidosis there was coexisting testicular cancer requiring additional treatment. We therefore advise caution in the interpretation of the clinical and histological findings in these patients, and recommend thorough investigation of all such cases.

Adult↗

Sites of relapse in seminoma treated with single agent carboplatin chemotherapy: implications for further management.

Between 1983 and 1990, 66 patients were treated with single agent carboplatin for advanced seminoma, and sites of relapse have been analysed with respect to sites involved before chemotherapy. Fourteen relapses were evaluable, and relapse was confined to node groups affected before chemotherapy, or those immediately adjacent, in seven patients. At present it is unclear whether single agent carboplatin should be the initial chemotherapy for seminoma, but if it is employed there may be a role for local adjuvant radiotherapy after carboplatin chemotherapy.

Adult↗

Surveillance following orchidectomy for stage I testicular seminoma.

An analysis of the primary tumour histopathology was performed on 103 patients managed by orchidectomy and surveillance for stage I seminoma. Patients have been followed for 14-141 months (median 62 months) after orchidectomy. Seventeen patients relapsed, the probability of remaining relapse free at 5 years being 82% (95% confidence intervals, 74%-88%). No patients died of progressive germ cell tumours. The only significant histological factor predicting relapse was the presence of lymphatic and vascular invasion. Four of 42 patients with neither lymphatic or vascular invasion recurred, nine of 53 patients with either lymphatic or vascular invasion recurred and three of eight cases with both lymphatic and vascular invasion recurred (P = 0.05-trend). Though initial recurrence was usually of moderate volume and confined to para-aortic nodes, eight patients were treated with chemotherapy either because of the extent of their initial relapse (four cases), or because of subsequent relapse (four cases). In view of the difficulties of identifying patients at risk and of detecting early relapse, surveillance for stage I seminoma should remain a research protocol.

Adult↗

Salvage radiotherapy in recurrent Hodgkin's disease.

Forty-four patients with Hodgkin's disease (HD) which relapsed after chemotherapy were treated with salvage radiotherapy (S-RT) with curative intent. Patients were aged 7 to 80 years (median 32 years) at the time of S-RT and the median follow-up from S-RT was 5 years (1-15). Nine patients had recurrent HD following first-line chemotherapy and thirty five patients had refractory HD. Salvage therapy consisted of radiotherapy alone in 25 and combined chemotherapy and radiotherapy in 19 patients. The overall CR rate of salvage therapy was 66%. The overall median survival of 44 patients was 4.6 years from S-RT with 46% 5 year and 40% 10 year survivals. Age (greater than 40 years) and progression free interval (less than or equal to 1 year) were adverse independent prognostic factors for survival on multivariate analysis. The 5 and 10 year progression free survivals were 38% and 23% respectively. Adverse independent prognostic factors for progression-free survival were extranodal site of recurrence and short progression free interval (less than or equal to 1 year). We conclude that radiotherapy with or without chemotherapy has a role in the salvage of patients failing chemotherapy, particularly in those with nodal disease and progression-free interval greater than 1 year.

Adolescent↗

The optimisation of carboplatin dose in carboplatin, etoposide and bleomycin combination chemotherapy for good prognosis metastatic nonseminomatous germ cell tumours of the testis.

An analysis of carboplatin dose response was performed in 121 patients with good prognosis metastatic nonseminomatous germ cell tumours (NSGCT) of the testis, referred to the Royal Marsden Hospital since 1984, who had been given combination carboplatin, etoposide and bleomycin (CEB) chemotherapy. With a median follow-up of 40 months (range: 7 to 85 months) nine patients (7%) have failed CEB. Carboplatin dose was analysed in all patients using body surface area (BSA) to derive a carboplatin dose per metre squared (mg/m2) and by calculation of a predicted serum concentration chi time (AUC: area under the curve) derived from the glomerular filtration rate (GFR), using the formula; Dose = AUC(GFR + 25). At a carboplatin dose of 400 mg/m2 or greater 2 out of 58 patients (3.4%) failed treatment while 7 out of 63 patients (11%) who received a dose less than this failed (p greater than 0.1). At an AUC of 5.0 mg.min/ml or greater, 2 out of 74 patients (2.7%) failed while 7 out of 47 patients (14.9%) who had an AUC less than this failed (p less than 0.05). There was evidence for a dose/response relationship at relatively low doses and the failure rate rose to 26% for doses less than 4.5 mg.min/ml (p less than 0.001) or 15.6% for doses less than 350 mg/m2 (p greater than 0.1). In view of the more precise determination of toxicity and efficacy it is recommended that carboplatin dose be based on the GFR.

Adolescent↗

The Second Medical Research Council study of prognostic factors in nonseminomatous germ cell tumors. Medical Research Council Testicular Tumour Working Party.

PURPOSE: To assess prognostic factors in a large population of patients with metastatic nonseminomatous germ cell tumors (NSGCT) arising in gonadal or extragonadal sites. PATIENTS AND METHODS: Data from 795 patients treated with chemotherapy between 1982 and 1986 in 13 centers were analyzed. Particular emphasis was placed on exact tumor measurements (eg, size of nodal masses, number of lung metastases), and the diagnostic pathology was also reviewed. Cox regression analysis was performed on these data. The patients were treated with a variety of cisplatin-containing chemotherapy regimens, 86% of which included etoposide. RESULTS: With median follow-up of 45 months, overall 3-year survival is 85%. The independently adverse features proved to be (1) the presence of liver, bone, or brain metastases; (2) raised marker levels (alpha-fetoprotein [AFP] level greater than 1,000 kU/L or beta subunit of human chorionic gonadotropin [HCG] greater than 10,000 IU/L [corrected]); (3) the presence of a mediastinal mass greater than 5 cm in diameter; (4) the presence of 20 or more lung metastases; (5) increasing age; and (6) absence of undifferentiated teratoma (embryonal carcinoma) or fibrous tissue from the primary tumor. CONCLUSIONS: The first four factors were used to define a simple prognostic classification. A good-prognosis group having none of these features comprised 67% of our patient population and had a 3-year survival of 93%. The remaining 33% of patients having at least one of these features had a 3-year survival rate of 68%. These patient groups are currently the subjects of international randomized clinical trials.

Adult↗

Medical Research Council prospective study of surveillance for stage I testicular teratoma. Medical Research Council Testicular Tumors Working Party.

PURPOSE: A prospective study of surveillance after orchidectomy alone in patients with stage I nonseminomatous germ cell testicular tumor (NSGCT) was performed to determine the relapse-free rate and to identify the histologic criteria that predict for relapse. PATIENTS AND METHODS: Three hundred ninety-six patients from 16 United Kingdom and one Norwegian centers were entered onto the study between January 1, 1984 and October 1, 1987 of whom 373 were eligible for analysis. In a previous retrospective study, we defined a prognostic index based on histologic criteria that identified a group of patients with a high risk of relapse. This index was based on the presence of venous and lymphatic invasion, undifferentiated cells, and the absence of yolk sac elements in the primary tumor. RESULTS: The 2-year actuarial relapse-free rate after orchidectomy was 75% (95% confidence interval, 71% to 79%), and the rate at 5 years was 73%. Five patients died of tumor or treatment-related complications, which resulted in a 5-year survival of 98%. The relapse-free rate in patients with three or four risk factors was 54%. CONCLUSIONS: This study confirms the safety of surveillance as a method of management and identifies a group of patients with a high risk of relapse. A prospective phase II study has been initiated to determine whether two courses of platinum-based adjuvant chemotherapy will prevent relapse in these high-risk patients.

Adult↗

Use of carboplatin in germ cell tumors of the testis.

The high cure rate among young men with metastatic testicular germ cell tumors heightens the issue of late treatment toxicity. Conventional combination chemotherapy based on cisplatin can be expected to cure 85% to 90% of patients with metastatic disease; however the cost of this success includes severe treatment side effects, including irreversible renal damage and the risk of neurotoxicity and ototoxicity. Carboplatin was investigated as a replacement for cisplatin in the treatment of these tumors because of its reduced toxicity. The Royal Marsden Hospital pilot studies have included 76 patients treated for metastatic nonseminoma with the combination carboplatin/etoposide/bleomycin between 1984 and 1988. The median follow-up at time of analysis was 24 months. The complete remission rate was 95% and the overall cause-specific survival was 98.5%. Also, 33 patients treated with single-agent carboplatin for advanced metastatic seminoma were followed for a median of 36 months. The actuarial progression-free survival was 79%, and 91% of patients were alive and disease-free. The results of these studies indicate that carboplatin has activity equivalent to cisplatin in germ cell tumors of the testis and is less toxic.

Adolescent↗