PURPOSE: Validation of biological dosimetry versus physical dosimetry in malignant haemopathy patients conditioned by total body irradiation (TBI) before bone marrow transplantation (BMT). PATIENTS AND METHODS: The scoring of chromosomal aberrations in peripheral lymphocytes irradiated in vivo was used to perform the biological dosimetry. The data were compared to those obtained with healthy volunteers' total blood exposed to in vitro irradiation with linear accelerator doses (0.2, 0.5, 0.75, 1, 2, 3, 4 and 5 Gy) for dose-response curves. In experimental animal models, can in vivo and in vitro responses be considered as being the same? All the published human data are based on retrospective dose evaluation with very large uncertainties on the dose precisely delivered to the subject. TBI before BMT was taken as a model where the dose calculation results from the physical method, with homogeneous beam and dose delivered precisely along the entire organism. In vivo response allows us to validate biological dosimetry in 15 adult patients (female + male), before (D = 0 Gy) and after the first fraction of 1.8 Gy, delivered by a linear accelerator (18 MV, dose-rate of 15.8 cGy/min-1). Two methods, conventional cytogenetics (CCG) and fluorescent in situ hybridization (FISH painting) of chromosome 4 were respectively used to analyze the unstable chromosome aberrations and stable chromosome aberrations. RESULTS: Healthy volunteer lymphocytes, before irradiation, yielded 0.1% dicentrics and 0.3% translocations of chromosome 4, with 2.5% for the whole genome. Patients before irradiation had 2% dicentrics and 11.48% chromosome 4 translocations for the whole genome. In the 15 patients, for a physical dose of 1.8 Gy, the evaluated biological dose was 1.93 Gy (95% CI: 1.85-2.05 Gy) with conventional cytogenetics and 2.06 Gy (95% CI: 1.75-2.15 Gy) with FISH. CONCLUSION: These results, in which the biologically estimated dose is in complete agreement with the dose calculated by physical dosimetry in the homogeneous irradiation model, suggest the validation of biological dosimetry in TBI conditioning.

Adolescent↗

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[131I]metaiodobenzylguanidine therapy in 20 patients with malignant pheochromocytoma.

Twenty patients, 16 male and 4 female (aged 11-76 years), with metastatic pheochromocytoma were treated in our Institution between 1985 and 1990. Metastases occurred in all patients: at presentation in 11 patients, with a 10 to 30 month delay in 7 patients, and 9 and 28 years later respectively in 2 patients. Catecholamines hyperproduction was present in all patients. Metaiodobenzylguanidine (MIBG) uptake was found in 16 patients after a diagnostic dose and only after a therapeutic dose in 1 patient. Surgery was performed on primary tumor (18 patients) and on distant metastases (10 patients). 131I-MIBG therapy was performed in 11 patients, 9 of whom were evaluable. The cumulative activity ranged from 3.7 to 26.3 GBq (100 to 711 mCi) in 1 to 6 courses. We observed symptomatic improvement (5 patients) and partial tumor response in 2 patients, which lasted for 28 and 9 months respectively, terminating with a rapidly progressing disease involving the bone marrow. Stabilisation was observed in 3 patients. Moderate myelosuppression occurred in 4 patients. Fifteen patients died with a median survival of 16 months (range 3-60). Response to therapy was poor and further evaluation of the presently available therapeutic approaches is needed.

3-Iodobenzylguanidine↗

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[Control of perfusion by angioscintigraphy during hepatic intra-arterial chemotherapy].

Intra-arterial hepatic chemotherapy is effective in the treatment of liver metastases, and it has been used at the Gustave Roussy Institute since 1983. During laparotomy, arterial catheters are introduced usually into the gastroduodenal artery, and they are connected either to a subcutaneous access or to an implantable pump. Seventy-one patients with liver metastases from colorectal adenocarcinoma were examined by angioscintigraphy to evaluate the quality of liver perfusion. Our technique uses three radioactive compounds and makes it possible to obtain a standard liver scintigram with technetium 99-colloidal rhenium sulphur, a dynamic view of liver arterial perfusion by injection of pure technetium 99 pernechtate, and a static mapping of well-perfused territories after injection of technetium 99-labelled macroaggregated albumin. This technique is reliable to explain most of the problems encountered during intra-arterial hepatic chemotherapy. In our experience, the quality of perfusion was highly variable and had a prognostic value. Objective responses were more frequent in well-vascularized metastases (64 percent) than in metastases with hypoperfusion (36 percent). Survival was also better in the former case, with a median survival of 18 months as against 12 months (p = 0.028).

Antineoplastic Combined Chemotherapy Protocols↗

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