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Biomedical subjects

A Horwich

Publications and source records attributed to A Horwich.

At least 109 records · Page 6Linked to original sources
PubMed1994

Initial chemotherapy for stage II testicular non-seminoma.

A retrospective survival analysis was performed on 287 patients treated with chemotherapy following orchidectomy for stage II testicular non-seminoma between 1982 and 1986 at a number of centres in the United Kingdom and 1 centre in Norway. A total of 80 patients had lymphadenectomy for a residual mass after chemotherapy. In 17 of these cases the histology was undifferentiated malignancy, in 44 it was differentiated teratoma, in 18 there was necrosis only and in 1 case histology was unknown. The overall survival in 47 patients with initial stage IIA disease (nodes measuring < 2 cm in transverse diameter) was 98% [95% confidence interval (CI), 96%-100%] at 3 years. In 175 patients with stage IIB disease (nodal diameter, 2-5 cm) the 3-year survival was 96% (95% CI, 93%-99%) and in 65 patients with stage IIC disease (nodal diameter, > 5 cm) it was 84% (95% CI, 75%-93%). In stage IIA and stage IIB disease this approach leads to survival equivalent to that obtained with the approach of initial retroperitoneal lymph-node dissection.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Combined single course carboplatin with radiotherapy in treatment of stage IIA,B seminoma--a preliminary report.

Twenty-one patients with Stage IIA or B seminoma have been treated post orchidectomy by a single course of carboplatin prior to conventional radiotherapy in either the Royal Marsden Hospital or the Norwegian Radium Hospital during 1989-1993. Follow-up ranged from 8 months to 51 months with a mean of 36 months and median 34 months. All patients achieved complete remission and remain disease free. The main side-effects were nausea and vomiting while haematological toxicity was slight. There was no symptomatic peripheral neuropathy, ototoxicity or deterioration of renal function. This combined modality approach is rational, feasible, and effective, although a larger number of patients with longer term follow-up are needed for reasonable comparison with the use of infradiaphragmatic radiotherapy alone.

Adult↗
PubMed1994

Mortality and cancer incidence following radiotherapy for seminoma of the testis.

From the records of the Thames Cancer Registry, 859 patients were identified, who were treated with radiotherapy for seminoma of the testis between 1961 and 1985. Second cancer incidence and mortality and also causes of non-cancer deaths in the study population were examined. Fifty-one (6%) patients died of testicular cancer, 42 within 5 years of diagnosis. There were 42 second cancers (other than second testicular cancers), and 20 deaths from second cancer (expected, 22.1--non-significant). The only subtype of cancer with a notable excess was leukaemia (4 incident cases observed; 0.64 expected; relative risk 6.2, 95% C.I., 2.7-14.8, 95% C.I., 2.7-14.7). The overall death rate from causes other than testicular cancer was not elevated (82 observed, 82.06 expected). There was some suggestion of an increase in the risk of mortality with time; for 10 or more years after treatment the relative risk was 1.31 (95% C.I., 0.95-1.81). There was no evidence of excess non-cancer deaths (62 observed, 60 expected). We conclude that there is no definite evidence from this investigation of increased risk of mortality secondary to radiotherapy; however, the excess incidence of leukaemia may be treatment-related and the cohort will be followed further.

Adolescent↗
PubMed1994

Accelerated chemotherapy for poor prognosis germ cell tumours.

A pilot study has been completed of an innovative dose intensive chemotherapy schedule for poor prognosis patients with metastatic germ cell tumours referred to the Royal Marsden Hospital between August 1989 and January 1992. The rationale underlying the regimen was the use of an extremely short intercycle interval in order to counteract the potential of these tumours for rapid proliferation. The drug combination in the first phase incorporated a combination of cisplatin and carboplatin, infusional bleomycin and vincristine and this was followed by three cycles of bleomycin, etoposide and cisplatin (C-BOP/BEP). 21 patients with adverse presentations were treated with C-BOP/BEP. The median follow-up of surviving patients is 36 months (range 18-52 months). 1 patient died of disease, 1 died of a treatment complication while in remission and 1 further patient relapsed, and is in remission after radiotherapy and surgery. The 2-year overall survival rate was 90% [95% confidence interval (CI) = 77-100%]. We conclude that this approach may represent an improvement over standard chemotherapy and should be assessed in a multicentre setting.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Haematological toxicity of radiotherapy following high-dose chemotherapy and autologous bone marrow transplantation in patients with recurrent Hodgkin's disease.

17 patients with recurrent Hodgkin's disease received 21 courses of radiotherapy (RT) 1-23 months after high-dose chemotherapy and autologous bone marrow transplantation. WHO grade III-IV haematological toxicity, of median duration 38 days (range 4-236), was observed following 10 courses of radiotherapy in 9 patients. This haematological morbidity could be predicted with an 80.0% sensitivity when the pre-RT white cell count was < 5 x 10(9)/l or the platelet count < 100 x 10(9)/l. It occurred in 9/11 patients with initial stage III-IV disease, including all 6 given extended radiotherapy fields, but in no patients with initial stage II disease (chi 2 = 9.35, P < 0.005). Age, histology, the presence of B symptoms, performance status, previous radiotherapy or chemotherapy, the interval between autologous bone marrow transplantation and radiotherapy, the high-dose regimen used, and the radiotherapy dose or field size, did not appear to affect haematological toxicity. The median survival was 18 months from the date of starting radiotherapy. 7 patients remain alive and progression-free 8-51 months (median 21 months) after radiotherapy. Radiotherapy may contribute to durable remissions in patients with relapsed or residual Hodgkin's disease after autologous bone marrow transplantation, but significant haematological toxicity may be expected in those with mild pancytopaenia prior to radiotherapy, particularly with initial stage III or IV disease.

Adolescent↗
PubMed1994

Primary chemotherapy for stage II nonseminomatous germ cell tumors of the testis.

Between 1979 and 1989, 122 patients with clinical stage II testicular nonseminoma were treated with primary platinum-based combination chemotherapy following orchiectomy. Of the patients 58 had Royal Marsden Hospital stage IIA (nodes less than 2 cm. in diameter) and the other 64 had stage IIB (nodes 2 to 5 cm. diameter) disease. With a median followup after chemotherapy of 5.5 years, 118 patients (97%) were disease-free. Two patients died of progressive germ cell tumors, 1 of bleomycin toxicity and 1 of coincidental disease. The 5-year actuarial survival probability was 95% (95% confidence intervals 91 to 99%) and the 5-year failure-free survival probability was 92% (95% confidence intervals 88 to 97%). Tumor substage was not predictive of relapse but did indicate the probability of lymphadenectomy for a post-chemotherapy residual mass since this was performed in 17% of the patients with stage IIA disease and 39% with stage IIB disease (p < 0.05). Resected specimens contained mature teratoma (29), necrosis alone (5) or embryonal carcinoma (1). We conclude that for these clinical stages primary chemotherapy was as effective as primary lymph node dissection and a major operation was avoided in 68% of the cases.

Actuarial Analysis↗
PubMed1994

Peripheral blood involvement in non-Hodgkin's lymphoma detected by clonal gene rearrangement as a biological prognostic marker.

Peripheral blood from 67 patients with non-Hodgkin's lymphoma was examined at initial diagnosis for the presence of circulating lymphoma cells by DNA hybridisation using immunoglobulin and T-cell receptor gene probes. Clonal gene rearrangement was found in 31% (21/67) of patients and correlated with clinical stage, histological grade and bone marrow involvement. Clinical stage and the presence of lymphoma cells in peripheral blood were prognostic factors for progression-free survival in all patients on univariate analysis, but the detection of lymphoma cells was not independent of stage. It was also not a significant predictor for survival. In patients with intermediate- and high-grade lymphoma, the detection of lymphoma cells in peripheral blood was a significant prognostic factor for progression-free survival (PFS) and survival only on univariate analysis. The 3-year PFS was 17% in patients with circulating lymphoma cells compared with 75% if these were absent (P < 0.05). The presence of lymphoma cells in peripheral blood is associated with extensive disease and may be a biological marker of poor disease control. Sensitive techniques of detection should form part of large prospective studies in non-Hodgkin's lymphoma.

Adult↗
PubMed1994

Conformal radiotherapy at the Royal Marsden Hospital (UK).

Conformal radiotherapy seeks to allow increased intensity of radiation by reducing the volume of normal tissues within the treatment volume. Techniques have developed secondary to improvements in three-dimensional imaging and accessible treatment technology is based on computer-controlled multileaf collimators to create an irregular radiation beam shape. Preliminary clinical work in the Royal Marsden Hospital seeks to quantify the toxicity reduction achievable by conformal techniques in the context of a prospective randomized pelvic radiotherapy trial which has now recruited 240 patients. The data accumulated during this trial will allow comparison of conformal and conventional radiotherapy and also analysis of the impact of dose and volume of a particular organ on both acute and late toxicity. Assessments have revealed that conformal techniques reduced significantly the treatment volume of normal tissues, e.g. by a mean of 54% for rectum and 42% for bladder. However, a relationship between volume and acute toxicity has not been established. Late toxicity is currently being analysed. Dose escalation trials in thoracic and in pelvic tumours are planned.

Humans↗
PubMed1994

Prognosis of testicular teratoma differentiated.

OBJECTIVE: To determine whether the clinical course of patients with testicular teratoma differentiated (TD) and those with testicular teratoma undifferentiated justify a different follow-up protocol. PATIENTS AND METHODS: Between 1979 and 1989, 16 adult patients with testicular TD were treated at the Royal Marsden Hospital. These represented 2.7% of the 592 testicular teratoma patients seen during this period. With the exception of a propensity to involve the right testis (76%), there were no differences in clinical presentation between TD and non-TD histological subtypes. RESULTS: The mean follow-up was 55 months (range 7-137). Seven of the 16 patients had Stage I disease and were entered into surveillance programmes; one relapsed at 7 months. Ten men were treated with cisplatin or carboplatin-based chemotherapy for metastases, of whom three had had prior chemotherapy at other hospitals and were referred after relapse. In the seven previously-untreated chemotherapy group two patients failed. In the concurrent era, 375 patients with other subtypes of metastatic testicular non-seminoma were treated with chemotherapy and 47 (12.5%) failed (Progress Free Survival chi square (chi 2) = 2.73, P = 0.01). Although no difference in progression-free survival was demonstrated between TD and non-TD patients, the former had a worse overall survival probability (chi 2 = 9.02, P = 0.003); this may be an artefact due to the small number of events. CONCLUSION: Despite the apparently more benign histology, it is recommended that the management of adult TD should not deviate from the general principles established for other histological subtypes of testicular teratoma.

Adult↗
PubMed1993

Craniopharyngioma--a long-term results following limited surgery and radiotherapy.

Between 1950 and 1986 173 patients with craniopharyngioma were treated at the Royal Marsden Hospital with external beam radiotherapy either alone or following surgery. Four patients had complete tumour excision, 21 subtotal and 78 partial resection, 14 had biopsy alone, 34 aspiration alone and 22 had no surgery directed at tumour eradication. Seventy-seven (45%) were children (aged < 16 years). The 10 and 20 year progression-free survival (PFS) rates were 83% and 79%. There were no independent prognostic factors for PFS. The 10 and 20 year survival rates were 77% and 66% at a median follow-up of 12 years. After adjustment for mortality in the normal population, age and technique of radiotherapy (which corresponded with era of treatment) were significant independent prognostic factors for survival. The risk of death (corrected for mortality from natural causes and controlling for radiotherapy technique) for age groups 16-39 and > or = 40 was 0.58 and 0.40 respectively, relative to a risk of 1.0 for the age group < 16 years. Survival and PFS were not influenced by the extent of surgical excision. Visual field defect improved after radiotherapy in 36% of patients (38/106) and visual acuity in 30% (27/91). No patient developed radiation optic neuropathy. We conclude that limited surgery and radiotherapy achieve excellent long-term tumour control and survival with low morbidity.

Adolescent↗
PubMed1993

Conformal radiotherapy of the pelvis: assessment of acute toxicity.

During the last 3 years the Royal Marsden Hospital (RMH) has conducted a prospective randomised trial of conformal pelvic radiotherapy in which dose/volume data and acute toxicity scores have been determined prospectively. Pending completion of the trial, a preliminary analysis has been undertaken of the volume reductions achieved, and of some of the symptom scores. The average symptom score increased during radiotherapy, more markedly for bowel than bladder symptoms. In comparing total doses of 30-38 Gy with 56-65 Gy, watery bowel motions were more frequent with the higher doses (p = 0.013) but in the high-dose group neither this symptom nor tenesmus correlated with volume of rectum treated to at least 90% of the prescribed dose. We conclude that the assessment of the impact of volume on the level of acute symptoms in pelvic radiotherapy is complex, and requires analysis of a range of symptoms, dose levels and normal-tissue volumes. The degree of symptom reduction from conformal radiotherapy will emerge from the RMH randomised trial within the next 12 months.

Humans↗
PubMed1993

Primary malignant mediastinal germ cell tumours: improved prognosis with platinum-based chemotherapy and surgery.

A retrospective analysis was performed of 18 patients with primary malignant germ cell tumours of the mediastinum treated with platinum-based chemotherapy between 1977 and 1990. All seven patients with pure seminoma were treated initially with chemotherapy and four of these patients received additional mediastinal radiotherapy. Only one patient relapsed; his initial therapy had included radiotherapy and single-agent carboplatin and he was successfully salvaged with combination chemotherapy. With a follow-up of 11 to 117 months (median 41 months) all seven patients with seminoma remain alive and disease free giving an overall survival of 100%. Eleven patients had malignant non seminoma; following chemotherapy eight of these had elective surgical resection of residual mediastinal masses. Complete remission was achieved in nine (82%) patients, however, one of these patients died from bleomycin pneumonitis. With a follow-up of 12 to 113 months (median 55 months) eight of 11 (73%) patients with malignant mediastinal teratoma remain alive and disease free.

Adult↗
PubMed1993

Cancer Research Campaign review of radiobiology research.

The meeting was reviewed and summarised by Professor Herman Suit. He judged that the potential clinical gains from research in radiobiology were very great and likely to translate to improved cancer treatment in the near future. He was highly complimentary about the contribution of UK research in radiobiology and he indicated that this viewpoint was held widely in the United States, Europe and Japan. Radiobiological research was the basis for major clinical trials in radiotherapy undertaken by trial groups in all these countries. He felt that major contributions to current practice in radiotherapy had been the definition of dose response, the rationale for the use of radiotherapy against slowly responding tumours, and the understanding of repair differentials and of clonal proliferation in the design of clinical fractionation trials, leading to clear demonstration of benefit for altered fractionation in the treatment of head and neck cancer and in the treatment of bladder cancer. An important goal of research should be the development of predictive testing for radiation response employing multiple predictive tests of radiation sensitivity (survival at 2 Gy), cellular proliferation (potential doubling time) and identification of hypoxic cells, together with physiological parameters such as blood flow intratumoral pressure, thiol metabolism and activation and status of repair genes. In terms of improving differential response between tumour and normal tissues, further refinement of dose fractionation patterns would be needed, but also research should continue on the modification of response using drug/radiation protocols, targeting techniques, growth factors and other biological response modifiers to support normal tissues, and modulation of DNA repair. Professor Suit felt that the pace of research in radiobiology was most encouraging for the field of radiotherapy. There was a consensus that support for radiobiology needed to be matched by support for academic radiotherapy if potential research gains were to be translated into advances in treatment. He shared the view expressed by the Committee of Cancer Experts of the EORTC that improvements in cancer cure over the next decade were likely to derive from improvements in radiotherapy.

Cell Hypoxia↗
PubMed1993

Para-aortic lymphadenectomy after chemotherapy for metastatic non-seminomatous germ cell tumours: prognostic value and therapeutic benefit.

Between 1976 and 1990, 231 patients had excision of para-aortic lymph node masses remaining after chemotherapy for metastatic non-seminomatous germ cell tumours. The overall 5-year survival rate was 80%. Multivariate analysis of survival after surgery was performed and the following were found to be independent prognostic variables: completeness of surgical excision, pathology of excised mass, timing of surgery after chemotherapy (elective versus salvage) and year of treatment (before or after 1984). Para-aortic lymphadenectomy provided both therapeutic benefit and histological information of prognostic value in planning future treatment and follow-up. Size of mass and serum markers at the time of surgery were of no additional prognostic value once completeness of excision and pathology were taken into account. We therefore recommend that all residual masses should be removed soon after completion of chemotherapy.

Adolescent↗