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See detailPréoperative hyperfractionated accelerated radiotherapy (HART) in locally advanced rectal cancer (LARC) immediately followed by surgery. A prospective trial.
Coucke, Philippe ULg; Notter, M; Matter, M et al

in Radiotherapy & Oncology (2006), 79

Abstract Background and purpose: We aim to report on local control in a phase II trial on preoperative hyperfractionated and accelerated radiotherapy schedule (HART) in locally advanced resectable rectal ... [more ▼]

Abstract Background and purpose: We aim to report on local control in a phase II trial on preoperative hyperfractionated and accelerated radiotherapy schedule (HART) in locally advanced resectable rectal cancer (LARC). This fractionation schedule was designed to keep the overall treatment time (OTT) as short as possible. Patients and methods: This is a prospective trial on patients with UICC stages II and III rectal cancer. The patients were submitted to a total dose of 41.6 Gy, delivered in 2.5 weeks at 1.6 Gy per fraction twice a day with a 6-h interfraction interval. Surgery was performed within 1 week after the end of irradiation. Adjuvant chemotherapy was delivered in a subset of patients. Results: Two hundred and seventy nine patients were entered and 250 are fully assessable, with a median follow-up of 39 months. The 5-years actuarial local control (LC) rate is 91.7%. The overall survival (OS) is 59.6%. The freedom from disease relapse (FDR) is 71.5%. Downstaging was observed in 38% of the tumors. Conclusion: The actuarial LC at 5 years is 91.7%, although we are dealing with stages II–III LARC, mainly located in the lower rectum (median distanceZ5 cm). The pattern of failure is dominated by distant metastases and treatment intensification will obviously require a systemic approach. q 2006 Elsevier Ireland Ltd. All rights reserved. Radiotherapy and Oncology 79 (2006) 52–58. [less ▲]

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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 detailRadiation therapy alone or combined surgery and radiation therapy in squamous-cell carcinoma of the penis?
Zouhair, A; COUCKE, Philippe ULg; Jeanneret, W et al

in European Journal of Cancer (2001), 37

Abstract To assess the prognostic factors and the outcome in patients with squamous-cell carcinoma of the penis, a retrospective review of 41 consecutive patients with non-metastatic invasive carcinoma of ... [more ▼]

Abstract To assess the prognostic factors and the outcome in patients with squamous-cell carcinoma of the penis, a retrospective review of 41 consecutive patients with non-metastatic invasive carcinoma of the penis, treated between 1962 and 1994, was performed. The median age was 59 years (range: 35±76 years). According to the International Union Against Cancer (UICC) 1997 classi®cation, there were 12 (29%) T1, 24 (59%) T2, 4 (10%) T3 and 1 TX (2%) tumours. The N-classi®cation was distributed as follows: 29 (71%) patients with N0, 8 (20%) with N1, 3 (7%) with N2 and 1 (2%) with N3. Forty-four per cent (n=18) of the patients underwent surgery: partial penectomy with (n=4) or without (n=12) lymph node dissection, or total penectomy with (n=1) or without (n=1) lymph node dissection. 23 patients were treated with radiation therapy alone, and all but 4 of the patients who were operated upon received postoperative radiation therapy (n=14). The median follow-up period was 70 months (range 20±331 months). In a median period of 12 months (range 5±139 months), 63% (n=26) of the patients relapsed (local in 18, locoregional in 2, regional in 3 and distant in 3). Local failure (stump in the operated patients, and the tumour bed in those treated with primary radiation therapy) was observed in 4 out of 16 (25%) patients treated with partial penectomy postoperative radiotherapy versus 14 out of 23 (61%) treated with primary radiotherapy (P=0.06). 15 (83%) out of 18 local failures were successfully salvaged with surgery. In all patients, 5- and 10-year survival rates were 57% (95% con®dence interval (CI), 41±73%) and 38% (95% CI, 21± 55%), respectively. The 5-year local and locoregional rates were 57% (95% CI, 41±73%) and 48% (95% CI, 32±64%), respectively. In patients treated with primary radiotherapy, 5- and 10-year probabilities of surviving with penis preservation were 36% (95% CI, 22±50%) and 18% (95% CI, 2±34%), respectively. In multivariate analyses, survival was signi®cantly in¯uenced by the N-classi®- cation, and surgery was the only independent factor predicting the locoregional control. We conclude that, in patients with squa- mous-cell carcinoma of the penis, local control is better in patients treated with surgery. However, there seems to be no di erence in terms of survival between patients treated by surgery and those treated by primary radiotherapy salvage surgery, with 39% having organ preservation. [less ▲]

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See detailRadiation therapy alone or combined surgery and radiation therapy in squamous-cell carcinoma of the penis?
Zouhair, A; COUCKE, Philippe ULg; Jeanneret, W et al

in European Journal of Cancer (2000), 37(2), 198203

To assess the prognostic factors and the outcome in patients with squamous-cell carcinoma of the penis, a retrospective review of 41 consecutive patients with non-metastatic invasive carcinoma of the ... [more ▼]

To assess the prognostic factors and the outcome in patients with squamous-cell carcinoma of the penis, a retrospective review of 41 consecutive patients with non-metastatic invasive carcinoma of the penis, treated between 1962 and 1994, was performed. The median age was 59 years (range: 35–76 years). According to the International Union Against Cancer (UICC) 1997 classification, there were 12 (29%) T1, 24 (59%) T2, 4 (10%) T3 and 1 TX (2%) tumours. The N-classification was distributed as follows: 29 (71%) patients with N0, 8 (20%) with N1, 3 (7%) with N2 and 1 (2%) with N3. Forty-four per cent (n=18) of the patients underwent surgery: partial penectomy with (n=4) or without (n=12) lymph node dissection, or total penectomy with (n=1) or without (n=1) lymph node dissection. 23 patients were treated with radiation therapy alone, and all but 4 of the patients who were operated upon received postoperative radiation therapy (n=14). The median follow-up period was 70 months (range 20–331 months). In a median period of 12 months (range 5–139 months), 63% (n=26) of the patients relapsed (local in 18, locoregional in 2, regional in 3 and distant in 3). Local failure (stump in the operated patients, and the tumour bed in those treated with primary radiation therapy) was observed in 4 out of 16 (25%) patients treated with partial penectomy ±postoperative radiotherapy versus 14 out of 23 (61%) treated with primary radiotherapy (P=0.06). 15 (83%) out of 18 local failures were successfully salvaged with surgery. In all patients, 5- and 10-year survival rates were 57% (95% confidence interval (CI), 41–73%) and 38% (95% CI, 21–55%), respectively. The 5-year local and locoregional rates were 57% (95% CI, 41–73%) and 48% (95% CI, 32–64%), respectively. In patients treated with primary radiotherapy, 5- and 10-year probabilities of surviving with penis preservation were 36% (95% CI, 22–50%) and 18% (95% CI, 2–34%), respectively. In multivariate analyses, survival was significantly influenced by the N-classification, and surgery was the only independent factor predicting the locoregional control. We conclude that, in patients with squamous-cell carcinoma of the penis, local control is better in patients treated with surgery. However, there seems to be no difference in terms of survival between patients treated by surgery and those treated by primary radiotherapy ±salvage surgery, with 39% having organ preservation. [less ▲]

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See detailA survey on staging and treatment in uterine cervical carcinoma in the Radiotherapy Cooperative Group of the European Organization for Research and Treatment of Cancer
Coucke, Philippe ULg; Maingon, P; Ciernik, I et al

in Radiotherapy & Oncology (2000), 54

Abstract Background: The treatment outcome of advanced stage uterine cervical carcinoma remains unsatisfactory. In order to elaborate a novel trial within The Radiotherapy Cooperative Group (RCG) of the ... [more ▼]

Abstract Background: The treatment outcome of advanced stage uterine cervical carcinoma remains unsatisfactory. In order to elaborate a novel trial within The Radiotherapy Cooperative Group (RCG) of the European Organization for Research and Treatment of Cancer (EORTC), we conducted a survey in 1997±1998 to determine the variability of pre-treatment assessment and treatment options. The variability of choosing surgery, de®ned radiation therapy techniques and chemotherapy are investigated, as well as the center's choices of future treatment strategies. Methods: Fifty two of 81 RCG centers from the RCG have participated in the survey. As one would expect, there is a large variation in the techniques used for pretreatment evaluation and treatment options. There is no `standard' for reporting acute and late side effects. Chemotherapy is used neither systematically nor uniformly, and some centers continue to use neadjuvant chemotherapy modalities. Results: Furthermore, the survey reveals that there is a strong demand for the reduction of overall treatment-time, for clinical investigation of novel combined modality treatment strategies, especially chemo±radiation therapy, and also for the use of new radiation sensitizers. Conclusion:We conclude that a more homogeneous approach to the pretreatment evaluation as well as treatment techniques is required in order to allow adequate quality control in any future trial of the RCG in the EORTC.q2000 Elsevier Science Ireland Ltd. All rights reserved. [less ▲]

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