Radiotherapy update.
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Combined Modality Therapy↗
Biomedical subjects
A Horwich
Publications and source records attributed to A Horwich.
Infradiaphragmatic Hodgkin's disease.
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Abdominal Neoplasms↗
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↗
Intracardiac metastases from germ cell tumours--an unusual but important site of metastasis.
Two cases of intracardiac deposits from testicular teratomas diagnosed by echocardiography and angiocardiography, respectively, are described. The importance of recognizing this as an uncommon site of metastasis from germ cell tumours is discussed.
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↗
Treatment of seminoma.
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Biomarkers, Tumor↗
Combination chemotherapy with bleomycin, etoposide and cisplatin (BEP) for metastatic testicular teratoma: long-term follow-up.
127 men with previously untreated non-seminomatous germ cell tumours (NSGCT) of the testis were given BEP chemotherapy (bleomycin, etoposide and cisplatin) between 1979-1986. Long-term follow-up (median 65 months) has shown an overall 5 year survival of 87.2% (95% confidence limits 81.1%-93.3%). Outcome was related to both tumour volume and serum marker levels of alpha-fetoprotein (alpha FP) and beta human chorionic gonadotropin (HCG), with 5 year actuarial survivals of 97.8%, 72.2% and 26.7% respectively for small, large and very large volume disease defined by Medical Research Council criteria, and 91.2% and 60.8%, respectively, for men with low (alpha FP less than or equal to 500 kU/l and HCG less than or equal to 1000 iU/l) or high serum marker levels. 79 men (62%) had a complete radiological and serum marker response to chemotherapy alone; residual masses postchemotheraphy were resected in 39 patients (31%), showing undifferentiated tumour in only 6 (15%). 23 of the 127 patients (18%) failed to respond or developed recurrent disease after BEP; only 5 were successfully salvaged. Myelotoxicity of treatment was mild with grade 4 toxicity in 2% of chemotherapy courses and 3 episodes of neutropenic sepsis. Mean glomerular filtration rates fell by 15.6% between courses 1 and 4 of BEP. Bleomycin pneumonitis developed in 13% of cases with 1 fatality. So far 21 men have had children following chemotherapy, but semen analysis 12 months or more (median 36 months) after treatment showed azoospermia in 11 out of 54 (20%) men tested. BEP chemotherapy can be regarded as standard treatment for patients with metastatic NSGCT in low-risk categories, but more intensive therapy is required for advanced presentations. Strategies to develop "risk related" treatment are under investigation.
Adolescent↗
Carboplatin dose in combination chemotherapy for testicular cancer.
Carboplatin was given in escalating doses in combination with etoposide and bleomycin (CEB) to 36 patients with testicular cancer. The platelet nadirs but not the white cell nadir correlated significantly with the dose of carboplatin administered. The best correlation was seen with area under the curve (AUC) calculated from a knowledge of the glomerular filtration rate (GFR). A further 40 patients were treated with a carboplatin dose calculated to give an AUC of 4.6 or 5.0 mg.min/ml. From the first part of the study it was predicted that 5-10% of the patients would have significant thrombocytopenia with the first course of treatment. The observed incidence was in fact 5%. When dose escalation and reduction were carried out for platelet nadirs falling outside the range 50-100 x 10(9)/l the average cumulative dose after four courses of carboplatin was very similar to four times the starting dose. Furthermore, as many reductions as escalations were carried out. Thus a starting dose for carboplatin calculated to give an AUC of 5.0 mg.min/ml in the CEB combination is one which will produce an acceptable level of thrombocytopenia. The CEB combination was found to produce a cumulative suppression of platelet nadirs. A mean net fall in haemoglobin of 7.5-9.5% was seen with each cycle.
Antineoplastic Combined Chemotherapy Protocols↗
Current controversies in the treatment of testicular cancer.
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Carcinoma in Situ↗
Hodgkin's disease of the liver; prognosis and possible indications for radiotherapy.
A retrospective analysis of 56 patients presenting with Hodgkin's disease involving the liver between 1970 and 1984 revealed a 10-year survival probability of 44%. The actuarial 10-year continuous progression free survival was 42%. Presentation variables predicting for relapse in the liver included hepatomegaly (P less than 0.025) or focal lesions on isotope, ultrasound or CT scan (P less than 0.01). These factors may define a context for investigation of adjuvant hepatic irradiation following chemotherapy.
Antineoplastic Combined Chemotherapy Protocols↗