Biomedical subjects

Nicolas Mach

Publications and source records attributed to Nicolas Mach.

6 recordsLinked to original sources

PubMed2005

Use of a prospective risk analysis method to improve the safety of the cancer chemotherapy process.

OBJECTIVE: To perform a risk analysis of the cancer chemotherapy process, by comparing five different organizations. To quantitatively demonstrate the usefulness of centralization and information technologies, to identify residual risks that may be the target of additional actions. STUDY DESIGN: A reengineering of the process started in 1999 and was planned to be finished in 2006. The analysis was performed after the centralization and at the beginning of information technologies integration. SETTING: Two thousand two hundred beds university hospital, with medical, surgical, haematological, gynaecological, geriatric, paediatric oncological departments. Twelve thousand cancer chemotherapies each year. METHODS: According to the failure modes, effects and criticality analysis (FMECA) method, the failure modes were defined and their criticality indexes were calculated on the basis of the likelihood of occurrence, the potential severity for the patients, and the detection probability. Criticality indexes were compared and the acceptability of residual risks was evaluated. RESULTS: The sum of criticality indexes of 27 identified failure modes was 3596 for the decentralized phase, 2682 for centralization, 2385 for electronic prescription, 2081 for electronic production control, and 1824 for bedside scanning (49% global reduction). The greatest improvements concerned the risk of errors in the production protocols (by a factor of 48), followed by readability problems during transmission (14) and product/dose errors during the production (8). Among the six criticality indexes remaining superior to 100 in the final process, two were judged to be acceptable, whereas further improvements were planned for the four others. CONCLUSIONS: Centralization to the pharmacy was associated with a strong improvement but additional developments involving information technologies also contributed to a major risk reduction. A cost-effect analysis confirmed the pertinence of all developments, as the cost per gained criticality point remained stable all over the different phases.

Antineoplastic Agents↗

PubMed2004

Can concomitant-boost accelerated radiotherapy be adopted as routine treatment for head-and-neck cancers? A 10-year single-institution experience.

PURPOSE: Accelerated schedules are effective in overcoming repopulation during radiotherapy (RT) for head-and-neck cancers, but their feasibility is compromised by increased toxicity. The therapeutic ratio may be particularly favorable for 5-week regimens. This study reports the 10-year experience of a single institution in the routine use of concomitant boost RT as standard radical treatment in all but the most favorable stage patients. METHODS AND MATERIALS: Between February 1991 and June 2001, 296 patients (mean age, 59 years) were treated with concomitant boost RT either alone (67%) or combined with cisplatin-based chemotherapy (33%), with a median tumor dose of 69.9 Gy. Tumors were located in the oropharynx in 52%, hypopharynx in 20%, larynx in 15%, nasopharynx in 7%, and oral cavity in 6%. International Union Against Cancer Stage III-IV disease represented 77% of tumors. The median follow-up for surviving patients was 55 months (range, 10-138 months). RESULTS: The RT schedule was completed to the prescribed dose in all but 1 patient. Twenty patients (7%) had a treatment interruption (median, 5 days; range, 2-35 days). Grade 3-4 Radiation Therapy Oncology Group acute toxicity was observed in 77% of patients, and nutritional support was required in 110 patients (37%). For all patients, the 5-year actuarial locoregional control and disease-free survival rate was 72% and 61%, respectively. In a multivariate analysis, only T and N stage was significantly associated with locoregional control and disease-free survival. Grade 3-4 late toxicity occurred in 14%, mostly bone and cartilage necrosis. CONCLUSIONS: The present, moderately accelerated, concomitant boost regimen is logistically feasible, causing minimal inconvenience to the technical staff and yielding a high rate of patient compliance. Concomitant chemotherapy administration is feasible provided that patients are carefully selected and supportive care is introduced in a timely fashion. Considering the manageable toxicity and the satisfactory tumor control obtained, this regimen represents a good choice when considering implementation of an altered RT fractionation schedule as standard treatment for head-and-neck cancers.

Adolescent↗

PubMed2003

CD1d-restricted T cells regulate dendritic cell function and antitumor immunity in a granulocyte-macrophage colony-stimulating factor-dependent fashion.

CD1d-restricted T cells contribute to tumor protection, but their precise roles remain unclear. Here we show that tumor cells engineered to secrete granulocyte-macrophage colony-stimulating factor induce the expansion of CD1d-restricted T cells through a mechanism that involves CD1d and macrophage inflammatory protein 2 expression by CD8 alpha-, CD11c+ dendritic cells (DCs). The antitumor immunity stimulated by vaccination with irradiated, granulocyte-macrophage colony-stimulating factor-secreting tumor cells was abrogated in CD1d- and J alpha 281-deficient mice, revealing a critical role for CD1d-restricted T cells in this response. The loss of antitumor immunity was associated with impaired tumor-induced T helper 2 cytokine production, although IFN-gamma secretion and cytotoxicity were preserved. DCs from immunized CD1d-deficient mice showed compromised maturation and function. Together, these results delineate a role for CD1d-restricted T cell-DC cross talk in the shaping of antitumor immunity.

Animals↗

PubMed2003

Quality of life in patients with oropharynx carcinomas: assessment after accelerated radiotherapy with or without chemotherapy versus radical surgery and postoperative radiotherapy.

BACKGROUND: In oropharyngeal carcinomas, it is assumed that the effectiveness of the different treatment approaches is roughly equivalent, whereas the functional outcome after radical radiotherapy (RT) is superior to that associated with primary surgery. The aim of this study is to assess quality of life (QoL) outcomes of patients after two treatment strategies: radical surgery with postoperative RT and accelerated concomitant boost RT with or without chemotherapy. METHODS: Sixty patients who were disease free at least 1 year after treatment of oropharynx carcinoma were studied. Forty had been treated with radical RT (median tumor dose, 69.9 Gy in 5.5 weeks), and 20 had been treated with primary surgery and postoperative monofractionated RT (median dose, 60.2 Gy). Seven of the former patients received chemotherapy concomitantly with, and one before, RT. Functional outcome was assessed by the subjective Performance Status Scale for Head and Neck cancer (PSSHN) and the general QoL by the European Organization for Research and Treatment of Cancer Core QoL questionnaire (EORTC QLQ-C30). The unpaired t test was used to assess for significant differences between means. RESULTS: By use of the PSSHN module, scores were generally higher in the RT group, with a significant difference in the speech subscale (p =.005), a trend for a significant difference for the eating in public subscale (p =.08), and an insignificant difference for the normalcy of diet subscale (p =.25). When analyzed by tumor stage, no significant differences were observed for T1-2 tumors, whereas for patients with T3-4 tumors highly significant differences favoring the RT group became evident for all three subscales. Although no significant differences were observed using the EORTC QLQ C-30 functional scales, patients treated with primary surgery reported significantly more dyspnea (28 vs 12, p =.04) and appetite loss (30 vs 13, p =.05). In patients with T3-4 tumors, trends toward better scores favoring the RT group were observed for physical, role, emotional, and social functions, as well as a significantly better score for pain symptoms. CONCLUSIONS: Although for early stages no clear advantage in QoL outcome was noted for the RT group compared with the surgery group, for advanced-stage disease an advantage favoring radical RT seemed apparent. For those patients, if an equivalency between the two treatment strategies could be assumed regarding oncologic results, then nonsurgical treatment should be considered the preferred option.

Activities of Daily Living↗

PubMed2002

In vivo evidence for the role of GM-CSF as a mediator in acute pancreatitis-associated lung injury.

Severe pancreatitis is frequently associated with acute lung injury (ALI) and the respiratory distress syndrome. The role of granulocyte-macrophage colony-stimulating factor (GM-CSF) in mediating the ALI associated with secretagogue-induced experimental pancreatitis was evaluated with GM-CSF knockout mice (GM-CSF -/-). Pancreatitis was induced by hourly (12x) intraperitoneal injection of a supramaximally stimulating dose of the cholecystokinin analog caerulein. The resulting pancreatitis was similar in GM-CSF-sufficient (GM-CSF +/+) control animals and GM-CSF -/- mice. Lung injury, quantitated by measuring lung myeloperoxidase activity (an indicator of neutrophil sequestration), alveolar-capillary permeability, and alveolar membrane thickness was less severe in GM-CSF -/- than in GM-CSF +/+ mice. In GM-CSF +/+ mice, pancreas, lung and serum GM-CSF levels increase during pancreatitis. Lung levels of macrophage inflammatory protein (MIP)-2 are also increased during pancreatitis, but, in this case, the rise is less profound in GM-CSF -/- mice than in GM-CSF +/+ controls. Administration of anti-MIP-2 antibodies was found to reduce the severity of pancreatitis-associated ALI. Our findings indicate that GM-CSF plays a critical role in coupling pancreatitis to ALI and suggest that GM-CSF may act indirectly by regulating the release of other proinflammatory factors including MIP-2.

Acute Disease↗

PubMedDate not supplied

Phase I trial of concomitant hyperfractionated radiotherapy with docetaxel and cisplatin for locally advanced head and neck cancer.

BACKGROUND: This study was conducted to determine the maximum tolerated dose of docetaxel when administered concomitantly with radical hyperfractionated radiotherapy and cisplatin in patients with locally advanced head and neck cancer. PATIENTS AND METHODS: Patients with stage III-IV tumors received radical radiotherapy of 74.4 Gy given in two daily fractions of 1.2 Gy for 6 weeks. Cisplatin was given once weekly on day 1 at a constant dose of 15 mg/m2. The starting dose of docetaxel was 10 mg/m2 once weekly on day 3, with planned escalation steps of 5 mg/m2. Main endpoints of the study were the maximum tolerated dose of docetaxel, acute toxicities, and the preliminary efficacy results. RESULTS: Twenty-five patients were enrolled. Median follow-up was 15 months (range: 4-40 months). Two of three patients presented with dose-limiting toxicities at the 15-mg/m2 dose of docetaxel (one patient presented with multiple grade 3-4 toxicities requiring hospitalization for management and another presented with multiple toxicities including life-threatening bronchoaspiration). Thus, the weekly docetaxel dose of 10 mg/m2 was considered the maximum tolerated dose. Nineteen patients were then treated with the maximum tolerated dose and no dose-limiting toxicities were observed. Radiotherapy was completed in all patients except one (median dose: 74.4; range: 73.2-74.4), and at least 80% of the scheduled cisplatin and docetaxel doses were given in 92% of the patients. Acute toxicities were dominated by grade 3 mucositis (92%) and grade 3-4 dysphagia (68%). The 2.5 year actuarial local control rate was 87.5%, and the disease-free survival rate was 75%. At the time of last follow-up, 23 patients were alive and two had died from cancer. No distant metastases were observed. DISCUSSION: In patients with locally advanced head and neck cancer, this study determined the maximum tolerated dose of docetaxel to be 10 mg/m2 administered once weekly when given concurrently with 74.4 Gy hyperfractionated radiotherapy and a weekly 15-mg/m2 dose of cisplatin. The toxicity profile and the encouraging results suggest that this new combination merits further investigation in a multi-institutional phase II trial.

Aged↗