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Biomedical subjects

M Brada

Publications and source records attributed to M Brada.

At least 127 records · Page 7Linked to original sources

The role of prophylactic spinal irradiation in localized intracranial ependymoma.

A review of the clinical literature on ependymoma, published between 1969 and 1989, was carried out to assess the influence of tumor grade and site, tumor control at the primary site, and extent of irradiation on the incidence of spinal seeding after initial treatment. The pooled data show that the incidence of seeding was 8.4% (7/83) for high grade tumors and 4.5% (6/132) for low grade tumors. Seeding occurred more frequently in infratentorial tumors than in supratentorial tumors. For high grade tumors the incidence was 0% (0/26) for supratentorial and 15.7% (6/38) for infratentorial lesions; for low grade tumors the respective incidence was 2.7% (1/37) and 5.5% (4/73). Spinal seeding was 9.5% (15/157) in the event of failure at the primary site compared to 3.3% (4/122) when local control was achieved. The development of spinal metastases was not influenced by the extent of irradiation. For high grade tumors the incidence was 9.4% (5/53) with spinal irradiation and 6.7% (2/30) without prophylactic treatment; for low grade tumors the respective values were 9.3% (4/43) and 2.2% (2/89). These results indicate that tumor grade, tumor localization, and control of the tumor at the primary site are all factors which may influence the risk of spinal seeding. On the present evidence spinal metastases are not prevented by prophylactic spinal irradiation, regardless of tumor grade and site.

Brain Neoplasms↗

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↗

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↗

Postoperative radiotherapy in the management of spinal cord ependymoma.

Fifty-eight patients with histologically verified spinal cord ependymomas were treated at the Royal Marsden Hospital and Atkinson Morley's Hospital between 1950 and 1987. The median age in this series was 40 years (range 1 to 79 years) and the male:female ratio was 1.8:1. Ten patients had tumors in the cervical cord and 10 in the thoracic cord; 14 tumors involved the conus medullaris and 24 the cauda equina. Forty ependymomas were grade I and 13 were grades II to IV (in five patients there was insufficient material for grading). Eleven patients underwent biopsy only, 33 had partial or subtotal resection, and 14 had complete resection. Forty-three patients received postoperative radiotherapy. The median follow-up period was 70 months (range 3 to 408 months). Cause-specific survival rates were 74% and 68% at 5 and 10 years, respectively. On univariate analysis, age, histological grade, postoperative neurological function, and era of treatment were significant prognostic factors for survival. The histological grade was the only significant independent prognostic factor. The relative risk of death from ependymoma was 9.0 for patients with tumor grades II to IV compared to grade I (p less than 0.005, 95% confidence interval 2.7 to 30). The survival rates of patients following complete excision were significantly better compared to those after incomplete surgery (p less than 0.025). The majority of completely resected neoplasms were low-grade cauda equina tumors. Despite incomplete surgery, 5- and 10-year progression-free survival rates following radical radiotherapy were both 59%, and cause-specific survival rates were 69% at 5 years and 62% at 10 years. This suggests that radiotherapy may achieve long-term tumor control in over half of those patients with residual spinal ependymoma.

Adolescent↗

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↗

Radiotherapy of brain tumours: reduced irradiation of normal brain.

We analysed the dose-volume distribution in normal brain in eight patients undergoing localized external beam radiotherapy for brain tumours. The results have been represented as integral dose-volume histograms and show that large volumes of normal brain receive clinically significant doses of radiation. A mean of 43% (range 24%-57%) of normal brain volume received more than 50% and a mean of 22% (range 9%-38%) received more than 85% of the maximum tumour dose. The amount of normal brain irradiated increased with enlarging target volume. With the use of customized shielding blocks the mean volume reduction of normal brain receiving more than 50% and 85% maximum tumour dose was 178 ml (median 183 ml; range 89-244 ml) and 110 ml (median 110 ml; 40-179 ml) respectively. This represents an average reduction of 13% and 8% of normal brain volume. Although clinically important this may not be sufficient for a significant improvement in therapeutic ratio.

Brain Neoplasms↗

ChlVPP combination chemotherapy for Hodgkin's disease: long-term results.

Two hundred and eighty-four patients with advanced Hodgkin's disease (HD) (stage II with poor prognostic features and stage III/IV) have been treated with the ChlVPP combination chemotherapy regimen (chlorambucil, vinblastine, procarbazine and prednisolone) in a single-centre unselected series. Median follow up is 92 months. Fifty-five patients had previously received radiotherapy but none had received previous chemotherapy. Eighty-five per cent of previously untreated patients and 91% of previously irradiated patients entered complete remission (CR); 71% and 68% of these respectively remain in CR at 10 years and 65% and 64% of each group respectively are alive at 10 years. On univariate analysis, age, stage, site of visceral disease and lymphocyte count predicted survival and on multivariate analysis age, absence of symptoms, absence of lung, liver or bone marrow disease and achieving a CR remained important predictors of survival. Acute toxicity was mild. The 10 year actuarial risk of acute leukaemia was 2.7%. This study adds further support to the view that chlorambucil is as effective and less toxic than mustine in combination chemotherapy for HD. We suggest that MOPP chemotherapy is no longer routinely indicated for HD.

Adolescent↗

Hypercalcaemia in patients with disseminated breast cancer.

Ninety-three patients with breast cancer and elevated serum calcium (Ca) had a median survival of 8.5 months from the diagnosis of hypercalcaemia. The presence of symptoms, visceral disease and level of serum Ca were independent prognostic indicators for survival on multivariate analysis. Patients without symptoms, no evidence of visceral disease and Ca less than or equal to 3.0 mmol/l had the best prognosis (median survival 3.5 years) when compared to patients with one adverse prognostic feature (median survival 16 months); two or more unfavourable features identified the worst prognostic category (median survival 2.5 months). Future studies of hypercalcaemia in malignancy should assess the influence of treatment on survival as well as symptom control and should take into account disease related prognostic factors in addition to the level of serum calcium.

Adult↗

Stage III Hodgkin's disease--long-term results following chemotherapy, radiotherapy and combined modality therapy.

215 patients with stage III Hodgkin's disease (HD) were treated at the Royal Marsden Hospital between 1963 and 1985 (median follow-up 9 years). The actuarial 5- and 10-year survival was 77 and 65%, respectively with 55 and 48% 5 and 10 year disease-free survival. Of 13 variables tested, age was the only independent prognostic indicator for survival on multivariate analysis. Patients aged under 40, 40-59 and over 60 years had a 10-year survival of 76, 41 and 8%, respectively (p much less than 0.001). Ninety-one patients were initially treated with combined chemotherapy and radiotherapy (combined modality therapy, CMT), 73 patients with radiotherapy (RT) and 51 patients with chemotherapy (CT) alone. Patients under 40 years treated with CMT achieved the best disease-free survival (10 year disease-free survival: CMT 68%; RT 38%; CT 45%). The observed survival advantage for CMT was not statistically significant. In patients aged greater than 40 there was no survival or disease-free survival advantage following CMT. Analysis of recurrence pattern confirmed that CMT improves initial disease control both at previously involved and uninvolved sites. Recurrences at previously uninvolved sites continued up to 6 years following CT, up to 8 years following CMT and up to 14 years after RT alone. These results indicate that only long-term follow-up gives the true picture of stage III HD.

Adolescent↗

Intensive induction chemotherapy for poor risk non-seminomatous germ cell tumours.

An increase in initial chemotherapy intensity was evaluated in 29 patients with high risk metastatic non-seminomatous germ cell tumours (NSGCT) of the testis, defined by the presence of multiple large lung metastases, liver, bone or brain metastases, or the combination of large abdominal mass with high serum concentration of the tumour markers alpha-foetoprotein (AFP) or beta subunit of human chorionic gonadotrophin (HCG) (AFP greater than 500 ku/l or HCG greater than 1000 iu/l). Four courses of bleomycin, vincristine and cisplatin (BOP) were given at 7 day intervals, followed by three courses of etoposide, cisplatin with or without bleomycin (BEP or EP) at 21 day intervals for a total of 13 weeks of chemotherapy. Twenty-three (85%) of 27 evaluable patients have remained continuously free from disease progression at a median of 24 months (range 14-38 months) from chemotherapy and the actuarial 2 year freedom from progression rate is 86% (95% CI = 73-99%). Three patients died from non-malignant causes, two of bleomycin pneumonitis and one from complications of cystic fibrosis. Thus cause specific overall survival in the total population of treated patients is 79%. With appropriate limitation of bleomycin dosage, this approach is well tolerated and results compare favourably with less intensive induction schedules based on initial 21-28 day cycles.

Adolescent↗

Changing patterns of relapse in Hodgkin's disease.

The patterns of early and late relapses (those occurring later than 3 years after diagnosis) in 432 patients achieving complete remission after treatment for stage I and II Hodgkin's disease at the Royal Marsden Hospital between 1964 and 1983 were studied to identify factors predicting for late relapse. The incidence of early relapse has fallen progressively in recent treatment eras as staging procedures and management have improved but in contrast there has been no decrease in the risk of late relapse. The incidence of late relapse was greater in patients treated with radiotherapy rather than combined modality therapy (P less than 0.05). However, patients who were clinically staged and treated with combined modality therapy retained as high a risk of relapse between 3 and 6 years as in years 2 and 3. The risk of late relapse was also greater in patients with stage II disease and in those without B symptoms at presentation. Patients falling into the higher risk categories for late relapse require continued close follow-up beyond 3 years to monitor for possible relapse.

Adolescent↗

Simple nontoxic treatment of advanced metastatic seminoma with carboplatin.

Between 1982 and 1986, 34 patients with advanced metastatic seminoma were treated with four to six courses of single-agent carboplatin administered at 400 mg/m2 every 4 weeks either on an outpatient basis or during 24-hour admissions. Patients with raised serum alphafetoprotein (AFP) or with multiple (more than three) lung metastases were excluded since these features may indicate a nonseminomatous component. In this series 20 patients were previously untreated except for orchiectomy, and 14 patients had received prior radiotherapy restricted to infradiaphragmatic nodal areas. Treatment was extremely well tolerated. No patient suffered renal damage, neurotoxicity, or ototoxicity, and there were no episodes of neutropenic septicemia, thrombocytopenic hemorrhage, or bruising. The actuarial 2-year survival was 94% (95% confidence intervals, 83% to 100%) with follow-up of 12 to 46 months from completion of carboplatin (mean, 26 months). The actuarial chance of remaining alive and free from progressive disease at 2 years was 80% (95% confidence intervals, 66% to 94%). Of six patients who relapsed, five are currently in remission 9 to 18 months after completion of salvage treatment. This level of antitumor activity is equivalent to that seen with aggressive combination regimens. Single-agent carboplatin should be considered the treatment of choice for advanced stages of malignant seminoma when limitation of toxicity is considered important; however, the rarity, especially of extranodal metastases from seminoma, leads to the need for further investigation using this approach.

Adult↗

Radiotherapy results in laparotomy-staged Hodgkin's disease.

Between 1970 and 1978, 131 patients with laparotomy-staged, supradiaphragmatic Hodgkin's disease were treated at the Royal Marsden Hospital with mantle radiotherapy, reserving chemotherapy for relapse. Forty-four patients relapsed at a total of 64 sites, the majority of which were infradiaphragmatic. Analysis of the factors predicting relapse showed that bulky mediastinal disease, and three or more sites of involvement at presentation significantly decreased disease-free survival in this group. Age above 60 years, high erythrocyte sedimentation rate (ESR) and adverse histology were of borderline significance. Although the majority (75%) of relapsed patients were salvaged with subsequent chemotherapy, it is suggested that patients with three or more sites of nodal involvement and bulky mediastinal disease would be managed best with initial combined modality therapy.

Adult↗