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See detailDecreased local control following radiation therapy alone in early stage glottic carcinoma with anterior commissure extention.
Azria, D; COUCKE, Philippe ULg; Matzinger, O et al

in Sonderbande zur Strahlentherapie und Onkologie (2004), 2

Purpose: To assess the patterns of failure in the treatment of early-stage squamous cell carcinoma of the glottic larynx. Patients and Methods: Between 1983–2000, 122 consecutive patients treated for ... [more ▼]

Purpose: To assess the patterns of failure in the treatment of early-stage squamous cell carcinoma of the glottic larynx. Patients and Methods: Between 1983–2000, 122 consecutive patients treated for early laryngeal cancer (UICC T1N0 and T2N0) by radical radiation therapy (RT) were retrospectively studied. Male-to-female ratio was 106 : 16, and median age 62 years (35–92 years). There were 68 patients with T1a, 18 with T1b, and 36 with T2 tumors. Diagnosis was made by biopsy in 104 patients, and by laser vaporization or stripping in 18. Treatment planning consisted of three-dimensional (3-D) conformal RT in 49 (40%) patients including nine patients irradiated using arytenoid protection. A median dose of 70 Gy (60–74 Gy) was given (2 Gy/fraction) over a median period of 46 days (21–79 days). Median follow-up period was 85 months. Results: The 5-year overall, cancer-specific, and disease-free survival amounted to 80%, 94%, and 70%, respectively. 5-year local control was 83%. Median time to local recurrence in 19 patients was 13 months (5–58 months). Salvage treatment consisted of surgery in 17 patients (one patient refused salvage and one was inoperable; total laryngectomy in eleven, and partial laryngectomy or cordectomy in six patients). Six patients died because of laryngeal cancer. Univariate analyses revealed that prognostic factors negatively influencing local control were anterior commissure extension, arytenoid protection, and total RT dose < 66 Gy. Among the factors analyzed, multivariate analysis (Cox model) demonstrated that anterior commissure extension, arytenoid protection, and male gender were the worst independent prognostic factors in terms of local control. Conclusion: For early-stage laryngeal cancer, outcome after RT is excellent. In case of anterior commissure extension, surgery or higher RT doses are warranted. Because of a high relapse risk, arytenoid protection should not be attempted. [less ▲]

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See detailPositive interactive radiosensitization observed in vitro with the combination of two nucleoside analogs (E)-2'-deoxy-2'-(fluoromethylene) cytidine (FMdC) and iododeoxyuridine (IdUrd).
Coucke, Philippe ULg; Cottin, E; Azria, D et al

in European Journal of Cancer (2004)

(E)-20-Deoxy-20-(fluoromethylene) cytidine (FMdC), an inhibitor of ribonucleotide diphosphate reductase (RR), is a potent radiation-sensitiser acting through alterations in the deoxyribonucleoside ... [more ▼]

(E)-20-Deoxy-20-(fluoromethylene) cytidine (FMdC), an inhibitor of ribonucleotide diphosphate reductase (RR), is a potent radiation-sensitiser acting through alterations in the deoxyribonucleoside triphosphate (dNTP) pool in the de novo pathway to DNA synthesis. The activity of thymidine kinase (TK), a key enzyme in the ‘salvage pathway’, is known to increase in response to a lowering of dATP induced by FMdC. Nucleoside analogues such as iododeoxyuridine (IdUrd) are incorporated into DNA after phosphorylation by TK. Radiation sensitisation by IdUrd depends on IdUrd incorporation. Therefore, we have investigated the radiosensitising effect of the combination of FMdC and IdUrd on WiDr (a human colon cancer cell-line) and compared it to the effect of either drug alone. We analysed the effects of FMdC and IdUrd on the dNTP pools by high-performance liquid chromatography, and measured whether the incorporation of IdUrd was increased by FMdC using a [125I]-IdUrd incorporation assay. The combination in vitro yielded radiation-sensitiser enhancement ratios of >2, significantly higher than those observed with FMdC or IdUrd alone. Isobologram analysis of the combination indicated a supra-additive effect. This significant increase in radiation sensitivity with the combination of FMdC and IdUrd could not be explained by changes in the dNTP pattern since the addition of IdUrd to FMdC did not further reduce the dATP. However, the increase in the radiation sensitivity of WiDr cells might be due to increased incorporation of IdUrd after FMdC treatment. Indeed, a specific and significant incorporation of IdUrd into DNA could be observed with the [125I]-IdUrd incorporation assay in the presence of 1 lM unlabelled IdUrd when combined with FMdC treatment. 2004 Elsevier Ltd. All rights reserved. [less ▲]

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See detailRadiothérapie externe accélérée postopératoire des carcinomes épidermoïdes localement évolués de la sphère ORL : étude prospective de phase II
Zouhair, A; COUCKE, Philippe ULg; Azria, D. et al

in Bulletin du Cancer. Radiothérapie : Journal de la Société Française du Cancer : Organe de la Société Française de Radiothérapie Oncologique (2003), 7

Abstract Purpose. – To assess the feasibility and efficacy of accelerated postoperative radiation therapy (RT) in patients with squamous-cell carcinoma of the head and neck (SCCHN). Patients and methods ... [more ▼]

Abstract Purpose. – To assess the feasibility and efficacy of accelerated postoperative radiation therapy (RT) in patients with squamous-cell carcinoma of the head and neck (SCCHN). Patients and methods. – Between December 1997 and July 2001, 68 patients (male to female ratio: 52/16; median age: 60-years (range: 43–81) with pT1-pT4 and/or pN0-pN3 SCCHN (24 oropharynx, 19 oral cavity, 13 hypopharynx, 5 larynx, 3 unknown primary, 2 maxillary sinus, and 2 salivary gland) were included in this prospective study. Postoperative RT was indicated because extracapsular infiltration (ECI) * Auteur correspondant. Adresse e-mail : abderrahim.zouhair@chuv.hospvd.ch (A. Zouhair). Cancer/Radiothérapie 7 (2003) 231–236 www.elsevier.com/locate/canrad © 2003 Éditions scientifiques et médicales Elsevier SAS. Tous droits réservés. doi:10.1016/S1278-3218(03)00041-6 was observed in 20 (29%), positive surgical margins (PSM) in 20 (29%) or both in 23 patients (34%). Treatment consisted of external beam RT 66 Gy in 5 weeks and 3 days. Median follow-up was 15 months. Results. – According to CTC 2.0, acute morbidity was acceptable: grade 3 mucositis was observed in 15 (22%) patients, grade 3 dysphagia in 19 (28%) patients, grade 3 skin erythema in 21 (31%) patients with a median weight loss of 3.1 kg (range: 0–16). No grade 4 toxicity was observed. Median time to relapse was 13 months; we observed only three (4%) local and four (6%) regional relapses, whereas eight (12%) patients developed distant metastases without any evidence of locoregional recurrence. The 2 years overall-, disease-free survival, and actuarial locoregional control rates were 85, 73 and 83% respectively. Conclusion. – The reduction of the overall treatment time using postoperative accelerated RT with weekly concomitant boost (six fractions per week) is feasible with local control rates comparable to that of published data. Acute RT-related morbidity is acceptable. [less ▲]

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