Treatment of seminoma.
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Biomarkers, Tumor↗
Biomedical subjects
A Horwich
Publications and source records attributed to A Horwich.
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↗
Inguinal and iliac lymph node involvement in germ cell tumours of the testis: implications for radiological investigation and for therapy.
The clinical details of 1191 patients with primary germ cell tumours of the testis seen at the Royal Marsden Hospital between 1977 and 1989 were reviewed in order to determine the incidence of inguinal or iliac node metastases. This was detected in 22 patients, 11 with inguinal and 11 with iliac lymphadenopathy. Seven of these patients had a history of maldescent and orchidopexy, and one patient had congenitally fused testes. Of the remaining 14 patients, eight had bulky para-aortic lymphadenopathy (5 cm or greater in diameter), one had histological evidence of breach of the tunica vaginalis by tumour, and in five patients no predisposing factors were identified. Eight patients had a seminoma, 11 a non-seminoma, and two a combined tumour. Inguinal or iliac nodes were significantly more common in the group of patients defined by bulky para-aortic disease or a history of maldescent and orchidopexy (15/267) than those without either factor (7/924, P less than 0.0004). Patients with a history of maldescent, congenital anomalies of the genitourinary system, or with bulky para-aortic disease, should routinely have the pelvis and inguinal regions included in a staging or follow-up CT scan. These factors should also influence the extent of the radiation field or of surgical dissection when these modalities are employed.
Cryptorchidism↗
The effect of carboplatin on renal function in patients with metastatic germ cell tumours.
Renal function was determined before and at varying times after chemotherapy in 62 patients with metastatic germ cell tumours treated with carboplatin. Eighteen patients were excluded because of urinary tract obstruction, leaving 44 evaluable patients treated with carboplatin either as a single agent (13 patients) or in combination with other agents (31 patients). No significant differences were observed in mean 51Cr-labelled Ethylenediamine tetraacetic acid (EDTA) clearances before and after carboplatin in either the group as a whole (P = 0.58), or when assessment at 1 month or less (P = 0.4), 3 months or less (P = 0.91), or later than 3 months (P = 0.38) were analysed. Carboplatin does not have significant renal toxicity when used at conventional dosage in patients with germ cell tumours.
Adolescent↗
Non-Hodgkin's lymphoma presenting with extradural spinal cord compression: functional outcome and survival.
Between 1971 and 1988, 20 patients with previously undiagnosed non-Hodgkin's lymphoma (NHL), of intermediate or high grade histology presented with extradural spinal cord compression. All had decompressive surgery. The first treatment after surgery was chemotherapy in nine and radiotherapy in 11 patients. At presentation 15% were ambulant and this improved to 55% after surgery; urinary continence improved from 30 to 80%. Mobility and sphincter control remained unchanged, regardless of subsequent therapy. Chemotherapy as the initial treatment modality after surgery, either alone or in combination with radiotherapy, did not jeopardise functional outcome. Mobility after surgery was an independent prognostic factor for survival, when corrected for age and stage at presentation (P = 0.04). The treatment of intermediate and high grade NHL presenting with spinal cord compression should be based on histology, extent of disease and age, as with other sites of presentation, but should also take into consideration the prognostic importance of post-surgical mobility.
Adolescent↗
Proliferation in human bladder carcinoma measured by Ki-67 antibody labelling: its potential clinical importance.
Ki-67 is a monoclonal antibody which recognises a human nuclear antigen expressed in proliferating cells. The antibody was used to assess proliferation in primary human bladder tumours from 64 patients. Ki-67 index (the number of Ki-67 positive tumour cells divided by the total number of tumour cells %) was derived from 59 tumours. A wide range of Ki-67 indices were recorded, range 3.0-65.8%, mean 20.2%. The Ki-67 index correlated with known prognostic factors: T stage (P = 0.002) and histological grade (P less than 0.001), early stage disease and more differentiated tumours having lower Ki-67 indices. Patients with invasive disease (21 patients) had significantly higher Ki-67 indices than those with non-invasive disease (P = 0.01). Patients with metastatic disease at presentation (four cases) all had a Ki-67 index of greater than or equal to 29%. Ki-67 antibody staining is a simple technique for assessing the proliferation fraction than can be performed on a small amount of tissue taken at routine biopsy without prior injection of thymidine analogues.
Aged↗
Imaging properties of polydioxanone and titanium ligating clips following para-aortic lymphadenectomy for testicular cancer.
Stainless steel ligating clips produce serious artefacts on CT scans. Polydioxanone (PDS) and titanium ligating clips were used in 15 patients during para-aortic lymphadenectomy for residual metastatic testicular teratoma following chemotherapy, and follow-up CT images were compared with those following the use of stainless steel ligating clips. PDS ligating clips did not produce any artefacts and were progressively absorbed. Titanium ligating clips produced artefacts similar to but less intense than those of stainless steel. PDS ligating clips should be used when follow-up CT scanning is important.
Constriction↗
Effectiveness of carboplatin, etoposide, and bleomycin combination chemotherapy in good-prognosis metastatic testicular nonseminomatous germ cell tumors.
The combination of carboplatin, etoposide, and bleomycin (CEB) was evaluated as initial chemotherapy in 76 patients with good-prognosis metastatic nonseminomatous germ cell tumors (NSGCT) between 1984 and 1988. The classification of eligible patients included Royal Marsden Hospital (RMH) stages IM, IIA, IIB, IIC, IIIA, IIIB, IV0ABCL1, and IV0ABL2. Four courses of combination chemotherapy were administered in a 21-day cycle, and surgical excision of residual mass was performed in 27 cases (23 laparotomies and four thoracotomies). At the time of analysis, median follow-up was 24 months from start of chemotherapy (range, 6 to 54 months). The 2-year cause-specific survival probability was 98.5%, the single cause-related mortality being caused by bleomycin pneumonitis. Five patients failed CEB chemotherapy, but all have been successfully salvaged with a combination of surgery and intensive chemotherapy, follow-up from completion of all treatment being 35 to 44 months. The toxicity of CEB included bone marrow suppression and alopecia in all patients but no significant neurotoxicity or ototoxicity, and minimal renal toxicity. Only four (5%) patients had a decrease in the glomerular filtration rate greater than 15%. In 51% of patients, the hemoglobin fell below 10 g/dL. The WBC count nadir was less than 1,500/microL in 11% of treatment cycles and in 16% the platelet nadir fell below 50,000/microL. Decreases in the WBC and platelet counts were of very brief duration. Only one of 310 CEB cycles was complicated by neutropenic sepsis, and there were no episodes of thrombocytopenic purpura or bleeding. We conclude that the CEB combination represents an effective alternative to cisplatin-based chemotherapy in good-prognosis NSGCT and that the replacement of cisplatin by carboplatin leads to reduced toxicity.
Adolescent↗
Orchidectomy alone for stage I seminoma of the testis.
Between 1983 and 1988, 113 patients with Stage I seminoma were managed after orchidectomy by surveillance rather than adjuvant radiotherapy. The actuarial risk of relapse at 3 years was 15.8% (95% confidence interval, 7.8% to 23.8%). All 13 patients who experienced a relapse are currently in remission (4 to 45 months after salvage therapy), although 5 suffered second relapses requiring further treatment. Close surveillance is a safe alternative to adjuvant radiotherapy in Stage I seminoma. However, the policy requires prolonged observation of patients with intensive use of resources. Therefore, adjuvant radiotherapy should be considered the treatment of choice.
Adult↗
The future of radiotherapy.
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Forecasting↗
The effects of single dose oral hydralazine on blood flow through human lung tumours.
Hydralazine has been shown to reduce tumour blood flow and to potentiate the cytotoxicity of melphalan and bioreductive agents in mice. In order to determine whether such a strategy might have clinical potential, a study was undertaken to investigate the effects of hydralazine on blood flow through human tumours. Twenty-two patients with carcinoma of the bronchus received a single oral dose of hydralazine in the range 25 to 150 mg (0.37-2.86 mg/kg) according to age and acetylator status. Tumour blood flow was assessed by single photon emission computed tomography (SPECT) performed 10 min following intravenous 99Tcm-HMPAO on two occasions 2-8 days apart, the second being performed 60 min after hydralazine administration. In 20 evaluable patients, hydralazine caused a 38% increase in blood flow through the whole tumour (p = 0.007) and a 28% increase in flow through the tumour centre (p = 0.03) with greater increases occurring in patients sustaining greater falls in peripheral resistance. Tumour vascular resistance fell indicating active vasodilation in arterioles supplying tumours. Side-effects due to hydralazine were reported by eight patients.
Administration, Oral↗
The management of early Hodgkin's disease.
Hodgkin's disease has provided a focus of academic attention for haematologists, radiotherapists and oncologists over the last 20 years but nevertheless there is considerable controversy over the management especially of early presentations. Options include performing a staging laparotomy and splenectomy with radiotherapy for pathological stage I and II disease, clinical staging with combined chemotherapy and radiotherapy, clinical staging with either extensive radiotherapy or with limited radiotherapy and close surveillance, or finally, clinical staging and treatment with chemotherapy alone. An appropriate management decision depends upon an assessment of the disease and also on the impact of treatment side-effects on the individual patient.
Antineoplastic Combined Chemotherapy Protocols↗
The growth rate of metastatic non-seminomatous germ cell testicular tumours measured by marker production doubling time--I. Theoretical basis and practical application.
Changes in serum tumour marker levels in non-seminomatous germ cell testicular tumours (NSGCTT) are used to monitor tumour growth and response to treatment. A novel method of calculating the actual tumour marker production (TMP) per day is reported; estimation of the rate of change of TMP is a measure of the tumour growth or regression rate. TMP is calculated mathematically from the rate of increase in serum marker level and its natural half life. TMP is assumed to be proportional to the number of marker producing cells in the tumour. TMP was calculated over the time between orchidectomy and the start of chemotherapy. The rate of increase in TMP with time is expressed as the marker production doubling time (MPDT) and is a measure of the growth rate. In a group of 51 patients with metastatic NSGCTT, TMP varied from 0.012 to 5985 iu/l/day (AFP) and 0.08-5404 iu/l/day (HCG). MPDT varied from 0.5 to greater than 80 days (45 cases) for AFP + ve patients and from 1.8 to greater than 80 days (34 cases) for HCG + ve patients; greater than 80% of cases had a MPDT less than or equal to 32 days. In 45/51 (88%) patients, there was no discrepancy in MPDT between markers. The use of changes in serum marker level to follow tumour progression and regression is simple, but the calculation of actual TMP provides clearer information about the change in number of marker producing cells and can be used as non-invasive method for measuring the tumour growth rate of metastatic disease and response to treatment.
Biomarkers, Tumor↗
The growth rate of metastatic nonseminomatous germ cell testicular tumours measured by marker production doubling time--II. Prognostic significance in patients treated by chemotherapy.
Tumour growth rates have been measured in metastatic non-seminomatous germ cell testicular tumours (NSGCTT) by estimating the rate of rise of tumour marker production (TMP). TMP was calculated for the time between orchidectomy and the start of chemotherapy in a group of 58 patients with metastatic NSGCTT treated with BEP combination chemotherapy (bleomycin, etoposide and cisplatin). Calculation of TMP (iu/l/day) took account of the continuing clearance of marker from the serum. TMP increased with time in 51 patients and this rise generally appeared to be exponential. The rate of this increase was expressed as the marker production doubling time (MPDT) and is a measure of the tumour growth rate. MPDT varied from 0.5 to greater than 80 days (45 cases) for AFP + ve patients and from 1.8 to greater than 80 days (34 cases) for HCG + ve patients. Patients who failed BEP first line therapy had shorter MPDTs than those who responded (AFP P = 0.08, HCG P = 0.003). It was found that patients with a MPDT less than or equal to 4 days were more likely to fail treatment than those who had a MPDT greater than 4 days (AFP P = 0.009, HCG P = 0.005). MPDTs were independent of initial serum marker concentration. Patients with small volume disease had longer MPDTs than patients with large volume disease (AFP P = 0.02, HCG P = 0.04). Rapid tumour growth rate reflected by short MPDT carries a poor prognosis in patients with NSGCTT treated by BEP chemotherapy.
Antineoplastic Combined Chemotherapy Protocols↗
Management of primary cerebral lymphoma with initial chemotherapy: preliminary results and comparison with patients treated with radiotherapy alone.
Between 1986 and 1988 10 patients with primary cerebral lymphoma (PCL) were treated with initial MACOP-B chemotherapy followed by radiotherapy. All demonstrated radiological response to chemotherapy but this did not predict final clinical outcome. The overall median survival was 14 months. Patients with poor MRC neurological performance status (NPS) 2-4 had a median survival of 5 months. Three of 7 patients with NPS 0-1 died and the median survival is 18 months with a median follow-up of 13 months (10-35 months). The results were compared to 25 patients with primary cerebral lymphoma treated between 1963 and 1986 with radiotherapy as the main treatment modality. The overall median survival was 16 months. Patients presenting with poor NPS (2 and 3) had worse survival (median survival 8 months) compared to patients with good NPS (median survival 22 months; p less than 0.025). Patients diagnosed and treated from 1982 to 1986 also had significantly worse prognosis when compared to earlier treated patients. The preliminary results of combined modality therapy are so far not significantly different when compared to historical series and we have to await long-term outcome before recommending combined modality therapy as the treatment of choice.
Adult↗