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Biomedical subjects

M Mahé

Publications and source records attributed to M Mahé.

13 recordsLinked to original sources

Long-term complications of total body irradiation in adults.

PURPOSE: To report long-term pulmonary, thyroid, and ocular complications in patients who had conditioning regimens including total body irradiation (TBI) before bone marrow transplantation (BMT). METHODS AND MATERIALS: Between June 1986 and December 1995, 478 patients received TBI in our institution. The present study includes 186 adult patients who had complete remission lasting one year or more after BMT. There were 108 males and 78 females. Median age was 36.5 years (range 15-60). Initial diagnoses were lymphomas (50%), acute lymphoid leukemias (16%), acute myeloid leukemias (16%), chronic myeloid leukemia (13%), aplastic anemia (3%), and myelodysplasia (2%). At the time of BMT, 43.5% of patients were in complete response and 56.5% in partial response. Treatment consisted of a single dose TBI at 10 Gy in 9% and fractionated TBI delivering 12 to 13.5 Gy in 6 fractions in 91%. From 1986 to October 1991, TBI was performed in lateral position with 9 MV energy (57% of patients) and thereafter in alternate prone and supine positions with 15 MV energy (43%). Chemical conditioning regimen was cyclophosphamide (60 mg/kg at D-4 and D-3) in 69% and CBV (cyclophosphamide 1500 mg/m(2) from D-6 to D-3, BCNU 300 mg/m(2) at D-6, VP-16 200 mg/m(2) from D-6 to D-4) in 25%. Fifty eight percent of patients received autologous and 42% allogeneic BMT. All patients had clinical, biologic, and functional examinations at one-year intervals. RESULTS: Median follow-up from BMT was 49 months (range 12-136). Late pulmonary effects were observed only in functional explorations, without clinical effect, including restrictive syndrome in 8% and alteration in the diffusing capacity of carbon monoxide in 12%. No patient showed clinical thyroid symptoms, and 10% developed biologic dysfunction: hypothyroidism (6.5%), thyroiditis (3%), and Basedow disease (0.5%). Ocular complications occurred in 29.5%, including cataract (15%), dry syndrome (13%), and keratitis (1.5%). In univariate and multivariate analysis, pulmonary complications were statistically increased by chronicle graft vs. host disease (GVHD) vs. no (p = 0.02), prone and supine vs. lateral TBI position (p = 0.02), and with 15 MV vs. 9 MV beam energy (p = 0.02). Cataract occurred less frequently with fractionated than with single-dose TBI (p = 0.000002). No differences were observed regarding age, sex, initial diagnosis, status at the time of BMT, conditioning chemotherapy regimen, and total dose of TBI. CONCLUSION: From this retrospective study it was shown that long-term complications of TBI were not symptomatic in most patients. The role of parameters of irradiation and especially position of treatment and beam energy should be emphasized and assessed with a longer follow-up.

Adolescent↗

Gene amplifications detected by fluorescence in situ hybridization in pure intraductal breast carcinomas: relation to morphology, cell proliferation and expression of breast cancer-related genes.

Investigation of early breast carcinogenesis is limited by the difficulty in obtaining cell cultures or adequate fresh frozen material and by the fact that available data from in situ techniques are interpreted in terms of various classification systems. Our studies in a series of pure ductal carcinomas in situ (DCIS) were conducted in accordance with the recommendations of the international Consensus Conference (Hum. Pathol., 28, 122-125, 1997) relative to processing, determination of lesion extent, and histological stratification primarily on nuclear grade (NG). A multifactorial study performed in 15 low- and 16 high-NG DCIS (68% detected by mammography) included the following: (1) morphological analysis of NG, necrosis, and architectural pattern; (2) detection of numerical genomic abnormalities at ERBB2, MYC, CCND1, Xq1.2 and 20q13 loci by fluorescence in situ hybridization on interphase nuclei; and (3) immunohistochemical determination of cell proliferation, p53 accumulation, hormonal receptors and bcl-2 expression on serial sections of formalin-fixed, paraffin-embedded specimens. High NG, comedo/solid pattern and necrosis were significantly associated with amplification at one or more loci, the number of amplified loci, amplification at the ERBB2 locus, absence of bcl-2 and hormonal receptor expression and high cell proliferation (p < 0.05). High NG and comedo/solid pattern were significantly associated with MYC amplification and p53 accumulation, and necrosis with CCND1 amplification (the only gene amplification detected in low NG DCIS). These data provide additional information on the early steps of breast carcinogenesis, in accordance with currently recognized criteria of histological classification.

Adult↗

Ovarian transposition by laparoscopy before radiotherapy in the treatment of Hodgkin's disease.

BACKGROUND: The use of inverted Y irradiation in the treatment of Hodgkin's disease with pelvic lymph node involvement can cause iatrogenic early menopause in young women as a result of ovarian exposure to radiation. Ovarian transposition protects the ovaries by removing them from the irradiation field. This surgical procedure, initially performed by laparotomy, can now be done by laparoscopy. METHODS: During the period July 1994 to April 1996, laparoscopic ovarian transposition was performed on 4 young women with Hodgkin's disease 1 week before inverted Y radiotherapy. The surgical procedure, complications, length of hospitalization, and hormonal, clinical, and biologic results were evaluated. RESULTS: The mean duration of hospitalization was 4 days, and there were no postoperative complications. Iatrogenic menopause did not occur in any of the patients during the mean follow-up period of 20.75 months (range, 6-35 months; median, 20 months). CONCLUSIONS: Laparoscopy offers many advantages over laparotomy for ovarian transposition. This procedure, which can be performed without opening the abdominal wall, is highly efficient, requires only a short period of hospitalization, and leads to few postoperative complications. Laparoscopy is an attractive alternative to laparotomy for ovarian transposition in young women with advanced Hodgkin's disease who require pelvic radiotherapy.

Adult↗

Final results of a randomized trial comparing chemotherapy plus radiotherapy with chemotherapy plus surgery plus radiotherapy in locally advanced resectable hypopharyngeal carcinomas.

After neoadjuvant chemotherapy, a routine conservative approach followed by salvage surgery was evaluated in terms of local control and survival in cases of advanced potentially resectable hypopharyngeal carcinoma. Between 1985 and 1989, 92 patients with T3 or T4-NO,N3 operable squamous cell hypopharyngeal carcinomas received three courses of neoadjuvant chemotherapy every 2 weeks involving a combination of cisplatin, 100 mg/m2, on day 1 and fluorouracil, 1 g/m2, on days 2 to 5, followed by total laryngopharyngectomy plus postoperative radiotherapy in 47 patients (arm A) or radiotherapy alone in 45 patients (arm B). Randomization was always performed prior to chemotherapy. The response rates of tumor and node to chemotherapy were, respectively, 67% in arm A versus 79% in arm B (P > 0.05) and 54% in arm A versus 73% in arm B (P > 0.05). Grade III or IV toxicity was similar, affecting 15% of patients and 7% of cycles in arm A versus 16% of patients and 6% of cycles in arm B. After a mean follow-up of 92 months, survival was statistically better (P = 0.04) in arm A (5-year overall survival, 37%; median survival, 40 months) than in arm B (19% and 20 months) because of a better local control rate (63% versus 39%; P < 0.01). Better results were obtained for mutilant surgery in terms of local control and overall survival, regardless of response to neoadjuvant chemotherapy.

Adult↗

Bispecific antibody and iodine-131-labeled bivalent hapten dosimetry in patients with medullary thyroid or small-cell lung cancer.

UNLABELLED: The purpose of this study was to estimate the dose delivered to tumor targets and normal tissues after two-step injection of an anti-CEA/anti-DTPA-In (F6-734) bispecific antibody and a 131I-labeled di-DTPA in-TL bivalent hapten in patients with medullary thyroid carcinoma (MTC) and small-cell lung cancer (SCLC). METHODS: Five patients with persistent disease or recurrences of MTC and five patients with primary SCLC or relapse were studied. In a first step, 0.1 to 0.3 mg/kg of F6-734 bispecific antibody was injected intravenously. Four days later, 6 nmole (5.8 to 9.8 mCi) of 131I-labeled di-DTPA in-TL bivalent hapten were injected. Quantitative imaging was performed during one week after the second injection. RESULTS: All 5 patients with MTC showed positive immunoscintigraphy (IS). In the smallest visualized and resected tumor (0.8 g), the fraction of injected activity per gram (% ID/g) was 0.1% at Day 3. IS was positive in 4 of the 5 patients with SCLC. The volume of the smallest visualized SCLC tumor was estimated at 11 +/- 2 ml, and tumor uptake was about 0.009% ID/g. Tumor dose estimates ranged from 4.2 to 174 cGy/mCi in patients with MTC and from 1.7 to 8 cGy/mCi in patients with SCLC. CONCLUSION: High absorbed dose values were calculated for small MTC recurrences. For SCLC recurrences the values were smaller but in the same range as those obtained by other investigators with the one-step technique in lymphoma.

Antibodies, Bispecific↗

[Efficacy of the combination of mitomycin, ifosfamide and cisplatin with irradiation for the treatment of cerebral metastasis in non small cell lung carcinoma].

We initiated prospective study testing efficacy of multidrug chemotherapy (cisplatin, ifosfamide, mitomycin) with irradiation in brain metastases of non small cell lung cancer at first diagnosis. Among 22 patients we obtained ten objective local responses (45%). Median survival was 7 months. Toxicity was mild (> 2 - OMS): hematologic = five patients; gastrointestinal = one patient. Among 11 patients who received chemotherapy before radiotherapy we had seven objective responses (patients evaluated after three courses of chemotherapy and before radiotherapy). This result indicates the interest of this protocol of chemotherapy in brain metastases. The association of this protocol of chemotherapy and radiotherapy appears effective, well tolerated and few toxic.

Adult↗

[Radioimmunotherapy in the treatment of cancers].

Radioimmunotherapy is a special form of internal radiotherapy which uses radiolabeled monoclonal antibodies. Until now, best results were achieved in refractory lymphomas and in ovarian cancer with minimal tumor residues. Several approaches are now under investigation to enhance tumor uptake and to improve hematologic tolerance. Recent advances in radiobiology are helpful to select future indications of this new method of treatment.

Humans↗

Use of multi-cell spheroids of ovarian carcinoma as an intraperitoneal radio-immunotherapy model: uptake, retention kinetics and dosimetric evaluation.

The purpose of this study, using multi-cell spheroids as an in vitro model of micrometastases of ovarian carcinoma for i.p. radio-immunotherapy, was to measure the uptake and retention kinetics of 111In-labeled F(ab')2 fragments of OC125 monoclonal antibody (MAb) in spheroids of the NIH:OVCAR-3 cell line and to estimate absorbed doses with beta-emitting radionuclides (kinetics was assumed to be similar to that of indium-111). With 0.2-mm-diameter spheroids at different MAb concentrations the highest binding value was determined. Retention kinetics showed a biological half-life of 50 hr. These data were used to calculate absorbed doses by integration of Berger's latest-point kernels. Mean absorbed doses when spatial distribution was considered to be uniform at the surface (no penetration) or throughout the spheroid (total penetration) were, respectively, 247 and 417 Gy with 153Sm, and 90 and 135 Gy with 90Y. Thus, the use of a similar MAb concentration and specific activity in patients should lead to high absorbed doses in i.p. radio-immunotherapy of micrometastases.

Antibodies, Monoclonal↗

[Inflammatory cancer].

Inflammatory carcinoma of the breast accounts for 1 to 4 p. 100 of breast cancers. It is a very serious form universally considered as a primarily systemic disease. The initial treatment is always systemic; primary surgery is contra-indicated. Most chemotherapeutic protocols result in objective response in 50 to 80 p. 100 of the cases. Depending on the response, local treatment consists of radiotherapy alone or combined with surgery. In spite of recent advances, the 5-year survival rate still ranges from 30 to 48 p. 100. Better prospects are in sight, however, owing to the study of prognostic factors, notably in the fields of oncogens and resistance to chemotherapy (MDR gene). Massive chemotherapy with autologous bone marrow transplantation or the use of haematopoietic growth factor will certainly play a part in treatment, but their value remains to be determined.

Antineoplastic Combined Chemotherapy Protocols↗

[Not Available].

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History of Medicine↗

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Botany↗