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Biomedical subjects

G Calais

Publications and source records attributed to G Calais.

At least 37 records · Page 2Linked to original sources

Cytotoxic drugs efficacy correlates with adipose tissue docosahexaenoic acid level in locally advanced breast carcinoma.

Experimental studies indicated that long-chain polyunsaturated fatty acids may increase sensitivity of mammary tumours to several cytotoxic drugs. To evaluate this hypothesis in breast cancer, we have prospectively studied the association between levels of fatty acids stored in breast adipose tissue and the response of the tumour to chemotherapy in 56 patients with an initially localized breast carcinoma. Adipose breast tissue was obtained at the time of biopsy, and individual fatty acids were measured as a percentage of total fatty acids using capillary gas chromatography. Patients then received primary chemotherapy, combining mitoxantrone, vindesine, cyclophosphamide and 5-fluorouracil every 4 weeks. Tumour size was reassessed after three cycles of chemotherapy. Tumour response was evaluated according to World Health Organization criteria. Complete or partial response to chemotherapy was achieved in 26 patients (47%). Level of n-3 polyunsaturated fatty acids in adipose tissue was higher in the group of patients with complete or partial response to chemotherapy than in patients with no response or with tumour progression (P < 0.004). Among n-3 polyunsaturated, only docosahexaenoic acid (22:6n-3) was significantly associated with tumour response (P < 0.005). In a logistic regression analysis taking into account age, body mass index and tumour size, 22:6 n-3 level proved to be an independent predictor for chemosensitivity (P = 0.03). These results suggest that, in breast cancer, 22:6 n-3 may increase the response of the tumour to the cytotoxic agents used.

Adipose Tissue↗

[Chemoradiotherapy of carcinomas of the upper aerodigestive tract].

The objective of this study was to review randomized trials which evaluated the effect of the radio-chemotherapy in head and neck carcinoma, and which compared radiotherapy alone vs the same local treatment plus chemotherapy. Over 40 such randomized trials have been performed, which generally showed no statistical difference between both arms. However few trials showed a benefit which is almost always in favor of the CT arm. Indeed, some trials of concomitant chemoradiotherapy have shown a statistically significant benefit in favor of the combined treatment. On the contrary, neoadjuvant chemotherapy generally leads to no detectable benefit compared to radiotherapy alone. These results have been reinforced by those of four randomized trials comparing neoadjuvant chemoradiotherapy and the same chemotherapy but given concomitantly with radiotherapy. The global effect of chemotherapy on survival of patients with head & neck squamous cell carcinoma has been recently evaluated by a meta-analysis based on individual patient data which included more than 10,000 patients from 63 randomized trials. The absolute survival rate benefit at 5 years is 4%, but is more pronounced in the concomitant combinations (8% at 5 years). In tumors classified as "T3" of the pharyngo-larynx, neoadjuvant chemotherapy followed by radiotherapy in good responders can avoid a total laryngectomy without significantly compromised survival. In the nasopharynx carcinoma, a few randomized studies have been performed, suggesting a benefit in favor of chemoradiotherapy. Finally, future randomized trials will determine what are the optimal chemoradiotherapy schedules, as well as determining what is the best radiotherapy (accelerated, hyperfractionated) to use in combination with chemotherapy.

Antineoplastic Agents↗

[Concomitant chemoradiotherapy of cancer of the esophagus].

Radiation therapy with concomitant chemotherapy is the standard treatment for non resectable esophageal carcinoma. For patients with operable tumors, surgery is the traditional treatment. However several data have suggested that preoperative chemo- and radiotherapy could improve therapeutic results. At the present time, no randomized trial has demonstrated, except for adenocarcinoma of the cardia, the benefit of preoperative treatment. Other randomized trials are needed to determine the role and the optimal modalities of these treatments. This is a review of the literature data in concomitant chemotherapy and radiation in the management of esophagus.

Adenocarcinoma↗

Mediastinal large-cell lymphoma with sclerosis refractory to conventional chemotherapy can respond after daily oral cyclophosphamide.

Mediastinal large-cell lymphoma with sclerosis (MLCLS) is a distinctive subtype of non-Hodgkin's lymphoma (NHL) with unique clinicopathology aspects and aggressive behavior. Prompt diagnosis and aggressive chemotherapy followed by consolidation radiotherapy may result in long-term survival in the majority of cases. However, a subset of patients do not respond to first-line or salvage treatment and have a poor prognosis. We report here a 27-year-old man with MLCLS resistant to several conventional chemotherapies and to radiotherapy who achieved a very good partial remission after one year's treatment with daily oral cyclophosphamide (100 mg/day). This is the first report of refractory MLCLS with good response to daily oral cyclophosphamide. This case suggests that daily oral monochemotherapy might be beneficial for some patients with mediastinal large-cell lymphoma with sclerosis refractory to conventional intravenous chemotherapies and radiotherapy.

Administration, Oral↗

Radiotherapy with high dose rate brachytherapy boost and concomitant chemotherapy for Stages IIB and III esophageal carcinoma: results of a pilot study.

PURPOSE: Radiotherapy (RT) and concomitant chemotherapy (CT) is the standard treatment for non resectable esophageal cancer. Usual total radiation dose is 50 Gy. In order to enhance local control rate a Phase II study was initiated to evaluate the feasibility of a combined treatment with an external radiation dose of 60 Gy and three cycles of concomitant CT, using the three main active drugs (CDDP, 5 FU and MMC), followed by a high dose rate (HDR) brachytherapy delivering 10 Gy. METHODS AND MATERIALS: Fifty-three patients, 48 men and 5 women, were entered in this study. Stages were evaluated with CT scan and with endoscopic sonography. Fifteen were Stage IIB, 38 Stage III. Treatment consisted of conventional fractionated RT to a total dose of 60 Gy delivered with 2 Gy per fraction, one fraction per day and five fractions per week. The CT regimen was a combination of Cisplatinum (CDDP) 20 mg/m2 and 5 Fluorouracil (5FU) 600 mg/m2 continuous infusion, from days 1-4 Mitomycin C (MMC) was given at 6 mg/m2 on day 1. Three cycles were administered on days 1, 22, and 43. Brachytherapy was delivered one week after the end of external radiation therapy. RESULTS: Full radiation therapy dose was delivered for 94% of the patients. CT compliance, evaluated on the mean relative dose-intensity was 85% for CDDP, 81% for 5FU and 51% for MMC. Overall grade 3 and 4 WHO toxicity rates were 23% and 7%, respectively. Haematologic toxicity was the most limiting factor. One patient died from treatment toxicity. Local control rate at one year was 74%. Three-year actuarial survival rate was 27%. Distant metastasis was the main cause of treatment failure. Swallowing score was good for 75% of the patients. Stage, performance status and weight loss were prognostic factors. CONCLUSION: This regimen with high dose RT, HDR brachytherapy and concomitant CT is feasible; however, a high level of haematologic toxicity was observed with the CDDP, 5FU and MMC regimen. Despite a poor compliance with CT, treatment results are very encouraging for patients with locally advanced disease.

Adult↗

Preoperative radiotherapy (RT) for rectal cancer: predictive factors of tumor downstaging and residual tumor cell density (RTCD): prognostic implications.

PURPOSE: To determine predictive factors and prognostic value of tumor downstaging and tumor sterilization after preoperative RT for rectal cancer. METHODS AND MATERIALS: Between 1977 and 1994, 167 patients with a histologically proven adenocarcinoma (70 T2, 65 T3, 29 T4, and 3 local recurrences) underwent preoperative RT. Median dose was 44 Gy (5-73 Gy). Surgery was performed in a mean time of 5 weeks after RT. Pathologic specimens have been reviewed by the same pathologist in order to specify the modified Astler Coller classification (MAC), and to quantify the residual tumor cell density (RTCD). RESULTS: According to the MAC, there was 9 stage 0 (5%), 10 stage A (6%), 103 stage B1-B3 (62%), and 45 stage C1-C3 (27%) tumors. Seventeen percent and 56% of the patients who received a dose > or = 44 Gy had respectively a 0-A and a B tumor, compared to 4 and 69% in those who received a dose < 44 Gy (p = 0.04). Tumor differentiation and a longer interval before surgery were significantly associated with a more frequent downstaging, and preoperative staging correlated well to the postoperative pathological findings. According to the RTCD, 62 tumors (37%) showed no or only rare foci of residual tumor cells (Group 1); 62 (37%) showed an intermediate RTCD (Group 2); and 43 (26%) a high RTCD (Group 3). No predictive factor of RTCD was statistically significant. In univariate analysis, postoperative staging was a significant prognostic factor, with corresponding 5-year overall survival rates in 0-A, B, and C stages of 92, 67, and 26% (p < 0.01). RTCD was not a prognostic factor. However, overall and disease-free survival rates for patients with complete pathologic response of 83% at 2 and 5 years suggested a better outcome in this subgroup of patients. CONCLUSION: The favorable influence of higher doses of preoperative RT on pathologic stage has been observed. Tumor differentiation, preoperative classification and time before surgery were the other predictive factors of tumor downstaging. However, there was no predictive factor of complete pathologic response. Even after preoperative RT, postoperative staging remained a prognostic factor.

Adenocarcinoma↗

Predictors of distant recurrence in clinical stage I or II endometrial carcinoma treated by combination surgical and radiation therapy.

A retrospective analysis of 201 patients with clinical Stage I or II endometrial carcinoma treated by combined surgery and radiation therapy from January 1976 to December 1992 is reported. The aim of the study was to determine predictors, if any, for distant recurrence. Twenty-eight patients (13.9%) in our series developed a recurrence. The most common sites were peritoneal carcinosis (28.6%), bones (28.6%), and lungs (21.4%). Seventy-eight percent appeared within 3 years, and actuarial survival rates at 12, 36, and 60 months after recurrence were 39.2, 14.2, and 7.1%, respectively. An analysis of predictive factors significant for the development of distant recurrence was performed. Significant factors by univariate analysis were age (P = 0.019), stage (P = 0.02), grade (P = 0.014), depth of myometrial invasion (P = 0.007), lymph node involvement (P < 0.001), and peritoneal cytology (P = 0.006). A multivariate analysis of these variables showed that lymph node involvement was the strongest predictor for distant recurrence.

Aged↗

[Role of radiotherapy in soft tissue sarcoma].

Radiation therapy is generally used as a surgical adjuvant in the treatment of soft tissue sarcomas. Postoperative external beam irradiation is the most commonly applied treatment. The majority of retrospective studies have suggested that radiation therapy could reduce the incidence of local recurrence. Radiation is recommended in case of deep tumor location, inadequate surgical margins and grade 3 tumor. A total dose of 55 to 65 Gy using large volume with initial field margin of 5 cm are recommended. Radiation therapy can also be delivered in preoperative fashion, but the majority of the studies have reported a higher wound complication rate. The value of brachytherapy for reducing the risk of local recurrence has been demonstrated in a randomized trial, especially for patients with high grade tumors. The combination of external radiation (40 to 45 Gy) and brachytherapy (15 to 20 Gy) seems to be the optimal adjuvant local strategy.

Brachytherapy↗

[Effect radiotherapy on postoperative staging and residual tumor cell density in rectal cancers].

PURPOSE: To determine predictive factors and prognostic value of tumor downstaging and sterilization after preoperative radiotherapy for rectal cancer. PATIENTS AND METHODS: Between 1977 and 1994, 167 patients with a histologically proven adenocarcinoma underwent preoperative radiotherapy (median dose, 44 Gy; mean time before surgery, 5 weeks). Pathologic specimens were reviewed by the same pathologist in order to specify the modified Astler Coller classification (MAC) and to quantify residual tumor cell density (RTCD). RESULTS: According to the MAC, there were nine stage 0 (5%), 10 stage A (6%), 103 stage B1-B3 (62%) and 45 stage C1-C3 (27%) tumors. Seventeen per cent and 56% of the patients who received a dose > or = 44 Gy presented with stage 0-A and stage B1-B3 tumors, respectively, compared to 4 and 69% of those who received a dose < 44 Gy (P = 0.04). Tumor differentiation and a longer interval before surgery were significantly associated with more frequent downstaging. According to the RTCD, 62 tumors (37%) showed no or only rare foci of residual tumor cells; 62 (37%) showed an intermediate RTCD and 43 (26%) a high RTCD. No predictive factor of RTCD was statistically significant. Only post-operative staging was a significant prognostic factor (P < 0.01). CONCLUSION: The favourable influence of higher doses of preoperative radiotherapy on pathologic stage has been observed. Tumor differentiation and time before surgery were the other significant predictive factors of tumor downstaging. Even after preoperative radiotherapy, post-operative staging retained its prognostic value.

Adenocarcinoma↗

Enhanced acute toxicity in oropharynx carcinoma treated with radiotherapy and concomitant cisplatin, 5-fluorouracil and mitomycin C.

The aim of this study was to establish the feasibility of giving concomitant radiotherapy and 3 cycles of chemotherapy with cisplatin (CDDP), 5-fluorouracil (5-FU) and mitomycin C (MMC) in locally advanced inoperable oropharyngeal cancer. From March 1990 to September 1993, 27 male patients (mean age 55 years) were included in this study. 3 patients (11%) were T2N0, 19 (70%) T3 (T3N0: n = 9, T3N1: n = 1, T3N2: n = 5, T3N3: n = 4), and 5 (19%) T4 (T4N0: n = 1, T4N1: n = 1, T4N2: n = 2, T4N3: n = 1). All patients received conventional radiotherapy delivering 70 Gy in 35 fractions and 52 days, and three cycles of chemotherapy starting on day 1, 21 and 42 with CDDP 20 mg/m2 and 5-FU 400 mg/m2 day 1 to day 4, and MMC 10 mg/m2 day 1. With a mean follow-up of 34 months (17-59), 10 patients (37%) were alive and free of disease. Among the 17 other patients, 8 died of cancer. Crude locoregional control rate was 78%, and probability of local control at 1 and 2 years was 85 and 80%, respectively. One- and 2-year survival rates were 48 and 31%, respectively, for both overall and disease-free survival. Grade 3 or 4 mucositis occurred in 22 patients (81%); enteral feeding was necessary for 63%; mean weight loss was 5.7 kg. Grade > 2 thrombocytopenia occurred in 11 patients (41%), grade > 2 neutropenia in 8 patients (29%), grade > 2 anaemia in 4 patients (15%). Febrile neutropenia or aplasia occurred in 5 patients (19%). 2 patients (7%) died during treatment of haematological or infectious complications related to the treatment. Another patient died 1 month after treatment with grade 4 thrombocytopenia and septicaemia. In conclusion, a high complete response rate has been achieved with this concomitant chemo- and radiotherapy, but with severe digestive and haematological toxicity. Addition of MMC to 5-FU and CDDP might have been responsible for this increased toxicity. This therapeutic combination is therefore not routinely feasible.

Adult↗

[Indications for castration in women treated for breast cancer].

Historically, castration has been the first endocrine treatment in breast carcinoma. In premenopausal metastatic patients, castration improves quality of survival during a median period of 10 months, in one third of patients. As adjuvant treatment, prophylactic castration can be an alternative to chemotherapy in patients with positive receptors. Prospective randomized trials are being conducted to define indications of each adjuvant treatment.

Antineoplastic Agents, Hormonal↗

Abdomino pelvic irradiation after second-look laparotomy for stage III ovarian carcinoma.

OBJECTIVE: The purpose of this retrospective analysis of 34 patients with stage III ovarian carcinoma was to review results and morbidity of whole abdominal irradiation after surgery and chemotherapy. METHODS AND MATERIALS: All of the 34 patients had reached a complete clinical remission after first cytoreductive surgery and chemotherapy. After second-look laparotomy each patient underwent whole abdominal irradiation. Except for two patients with chronic myelosuppression, the dose administered was of 22.5 Gy to the abdominal cavity with a boost of 22.5 Gy added to the pelvis. RESULTS: Three and 5-year overall survival rates were 62% and 43%, respectively. Three and 5-year disease-free survival rates were 53% and 38%. Twenty-three patients (68%) developed local relapse or local disease progression. Metastasis occurred in five cases and were always associated with an abdominal cavity recurrence. Residual disease after first cytoreductive surgery appeared as a prognostic factor in univariate analysis. Patients with unresected residuum had a 5-year survival probability of 35% versus 83% for patients without residual disease. We observed 12% grade-3 intestinal toxicities and one fatal case of radiation enteritis. CONCLUSION: Despite its curative potential, the long term benefit of whole abdominal irradiation in the multimodality treatment of advanced ovarian carcinoma must be evaluated in well designed controlled trials.

Antineoplastic Agents↗