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See detailAnalysis of Dose Volume Histogram Differences between High Dose Rate Brachytherapy and Intensity Modulated Radiotherapy for Prostate Treatment
Hermesse, Johanne ULg; Thissen, Benedicte ULg; Warlimont, Bernard ULg et al

in International Journal of Radiation, Oncology, Biology, Physics (2008), 72(1 (supplément)), 566

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See detailCarcinome intracanalaire (in situ) du sein : pouvons-nous raisonnablement éviter les radiothérapie pour certaines patientes opérées?
Coucke, Philippe ULg; Barthelemy, Nicole ULg; Jansen, Nicolas ULg et al

in Revue Médicale de Liège (2008), 63 (2)

Dans le cadre de la prise en charge multidisciplinaire du carcinome intracanalaire du sein (carcinome intra-canalaire in situ = DCIS = Ductal Carcinoma In Situ), on évoque souvent la possibilité de ... [more ▼]

Dans le cadre de la prise en charge multidisciplinaire du carcinome intracanalaire du sein (carcinome intra-canalaire in situ = DCIS = Ductal Carcinoma In Situ), on évoque souvent la possibilité de renoncer à la radiothérapie complémentaire après un geste de chirurgie conservatrice. S’il est vrai que la radiothérapie, dans ce contexte, n’apporte pas de bénéfice en survie, il n’en reste pas moins qu’on observe à long terme un effet bénéfique en contrôle local. Il existe un effet significativement marqué sur le taux de rechute de type DCIS et de type invasif dans les différentes études randomisées destinées à éclaircir la problématique du rôle de la radiothérapie. La question est de savoir si on peut distinguer un sous-groupe de patientes pour qui le contrôle local n’est pas modifié par l’adjonction d’une radiothérapie adjuvante. Pour l’instant, nous ne sommes pas à même de définir ce sous-groupe, car les critères de sélection n’ont pas été mis à l’épreuve dans le cadre d’un essai randomisé. Faute de ces données, il nous semble plus adéquat de proposer jusqu’à preuve du contraire, une radiothérapie aux patientes opérées, même si l’intervention est a priori radicale, mais conservatrice, et même si les facteurs pronostiques semblent plutôt favorables. Cependant, la radiothérapie n’est pas indiquée après une mastectomie. [less ▲]

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See detailLes tumeurs de la sphere ORL: standards de traitement et nouvelles approches en radiotherapie.
Coucke, Philippe ULg; Piret, Pascal ULg; Werenne, Xavier ULg et al

in Revue Médicale de Liège (2008), 63(3), 141-8

We intend to review the general value of radiotherapy in the management of head and neck cancer. Our aim is to define a treatment protocol which is evidence-based and therefore of use in daily clinical ... [more ▼]

We intend to review the general value of radiotherapy in the management of head and neck cancer. Our aim is to define a treatment protocol which is evidence-based and therefore of use in daily clinical practice. There is general agreement on the efficacy of the concomitant schedules combining radiotherapy and chemotherapy, both in the adjuvant setting as well as in the exclusive non-surgical approach. This however does not preclude further research aiming at optimizing the therapeutic index. As far as neoadjuvant chemotherapy is concerned, applied prior to radical local treatment, there are no conclusive data available which allows us to implement this treatment option in routine clinical practice. This approach deserves further investigations and patients should be entered in well designed prospective randomized trials. [less ▲]

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See detailLes standards de radiothérapie en gynécologie : cancer du col utérin
Coucke, Philippe ULg

in Gunaïkeia (2008), 13(5), 149-153

Sur base de la littérature, nous voulons faire le point sur ce qui peut être considéré comme une approche standard pour le traitement du cancer du col utérin. Nous évoquerons en particulier les questions ... [more ▼]

Sur base de la littérature, nous voulons faire le point sur ce qui peut être considéré comme une approche standard pour le traitement du cancer du col utérin. Nous évoquerons en particulier les questions suivantes: traitement adjuvant après chirurgie pour les stades précoces, la chirurgie adjuvante après une première chimio-radiothérapie pour les stades avancés, la place de la chimiothérapie néo-adjuvante ainsi que d’autres modalités destinées à augmenter l’effet anti-tumoral des radiations ionisantes. Introduction La prise en charge des cancers dans la sphère gynécologique nécessite une concertation multidisciplinaire ab initio. En effet, différentes approches peuvent être envisagées, et il est primordial de définir avant tout acte thérapeutique la séquence et la synchronisation des différentes modalités afin d’assurer au mieux un succès thérapeutique. La radiothérapie a un rôle central à jouer dans la prise en charge d’une patiente souffrant d’un cancer du col utérin. Une revue non exhaustive de la littérature publiée permet de déterminer sur la base des résultats d’essais randomisés ce qui peut raisonnablement être considéré comme une approche «standard». Cette approche permet aussi de facto de définir quels sont les points d’ombre qui méritent que l’on conduise des essais randomisés dessinés spécifiquement pour répondre à une question précise. [less ▲]

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See detailLes standards de radiothérapie en gynécologie: cancer du sein
Coucke, Philippe ULg

in Onco : Revue Multidisciplinaire d'Oncologie (2008), 2(4), 138-141

Introduction Les cancers gynécologiques, et en particulier les cancers mammaires, bénéficient d’une prise en charge multidisciplinaire et concertée. Dans le contexte multidisciplinaire, la radiothérapie ... [more ▼]

Introduction Les cancers gynécologiques, et en particulier les cancers mammaires, bénéficient d’une prise en charge multidisciplinaire et concertée. Dans le contexte multidisciplinaire, la radiothérapie externe tient un rôle important visant à consolider en premier lieu le contrôle local mais également à améliorer la survie. Par une revue de la littérature nous voulons décrire les «standards» établis, en particulier pour la composante radiothérapie de cette approche multidisciplinaire. Cette recherche de «standards» permet par ailleurs d’évoquer un certain nombre de questions restées à ce jour ouvertes et qui méritent d’être évaluées de façon prospective et randomisée.Conclusions La radiothérapie externe améliore significativement le contrôle local, à tel point qu’on ne peut s’abstenir de la proposer à toute patiente après chirurgie conservatrice, que ce soit pour une tumeur infiltrante ou un carcinome intra-canalaire. Après mastectomie, on retiendra l’indication si on objective une atteinte axillaire ou si d’autres facteurs sont présents tels que la taille tumorale, la proximité de la tumeur vis-à-vis de la marge de résection, l’atteinte cutanée et la présence d’une large composante d’emboles lympho-vasculaires. L’impact sur la survie de ce traitement adjuvant local n’est de loin pas négligeable puisque finalement comparable en chiffre absolu à l’impact sur la survie d’un traitement systémique. L’abstention thérapeutique n’est donc pas de mise, à l’exception de ces patientes traitées par mastectomie, chez qui aucune atteinte ganglionnaire n’est objectivée et chez qui aucun facteur tumoral ou pathologique ne semble indiquer un risque majoré de récidives locales. L’âge avancé de la patiente n’est pas une raison suffisante pour prôner l’abstention thérapeutique (28). La radiothérapie partielle du sein, très populaire aux USA, mérite que l’on s’y intéresse dans le cadre d’un essai prospectif randomisé. [less ▲]

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See detailInnovations technologiques en radiothérapie-oncologie
Coucke, Philippe ULg; Louis, Céline ULg; Bolle, Stéphanie

in Revue Médicale de Liège (2007), 62 (5-6)

InnovatIve technologIes In radIatIon oncology SUMMARY : At present, radiation oncology is again flourishing thanks to the development of highly accurate techniques as intensity modulated radiation therapy ... [more ▼]

InnovatIve technologIes In radIatIon oncology SUMMARY : At present, radiation oncology is again flourishing thanks to the development of highly accurate techniques as intensity modulated radiation therapy, stereotactic radiation therapy and hadrontherapy. These therapeutic modalities are made possible by the advent of image guided radiation therapy and respiratory gating that allows a better patient repositioning during the irradiation and between fractions. Nowadays, thanks to these recent technological advances, one can more easily conceive dose escalation, hypofractionation and combined treatment of radiation with sensitizing drugs and this together with a better protection of normal tissue aiming at, simultaneously, improved tumour control and better quality of life. This article describes these innovative technologies that, when integrated to other anti-tumoral therapeutic modalities, seem to be very promising. Keywords : - [less ▲]

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See detailSimultaneous alteration of de novo and salvage pathway to the deoxynucleoside thriphosphate pool by (E)-2'-deoxy-(fluoromethylene)cytidine (FMDC) and zidovudine (AZT) results in increased radiosensitivity in vitro.
Coucke, Philippe ULg; Cottin, Eliane; Laurent, A. et al

in Acta Oncologica (2007), 46

Abstract To test whether a thymidine analog zidovudine (=AZT), is able to modify the radiosensitizing effects of (E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC). A human colon cancer cell line Widr was ... [more ▼]

Abstract To test whether a thymidine analog zidovudine (=AZT), is able to modify the radiosensitizing effects of (E)-2'-Deoxy-(fluoromethylene)cytidine (FMdC). A human colon cancer cell line Widr was exposed for 48 hours prior to irradiation to FMdC. Zidovudine was added at various concentrations immediately before irradiation. We measured cell survival and the effect of FMdC, AZT and FMdC + AZT on deoxynucleotide triphosphate pool. FMdC results in a significant increase of radiosensitivity. The enhancement ratios (ER =surviving fraction irradiated cells/surviving fraction drug treated and irradiated cells), obtained by FMdC or AZT alone are significantly increased by the combination of both compounds. Adding FMdC to AZT yields enhancement ratios ranging from 1.25 to 2.26. FMdC reduces dATP significantly, with a corresponding increase of TTP, dCTP and dGTP. This increase of TTP, dCTP and dGTP is abolished with the addition of AZT. Adding AZT to FMdC results in a significant increase of the radiosensitizing effect of FMdC. This combination appears to reduce the reactive enhancement of TTP, dCTP and dGTP induced by FMdC while it does not affect the inhibitory effect on dATP. [less ▲]

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See detailEffect of timing of surgery on survival after preoperative hyperfractionated accelerated radiotherapy (HART) for locally advanced rectal cancer (LARC): Is it a matter of days?
Coucke, Philippe ULg; Notter, Markus; Matter, Maurice et al

in Acta Oncologica (2006), 45(8), 1086-1093

We intend to analyse retrospectively whether the time interval ("gap duration" = GD) between preoperative radiotherapy and surgery in locally advanced rectal cancer (LARC) has an impact on overall ... [more ▼]

We intend to analyse retrospectively whether the time interval ("gap duration" = GD) between preoperative radiotherapy and surgery in locally advanced rectal cancer (LARC) has an impact on overall survival (OS), cancer specific survival (CSS), disease free survival (DFS) and local control (LC). Two hundred seventy nine patients with LARC were entered in Trial 93-01 (hyperfractionated accelerated radiotherapy 41.6 Gy/26 Fx BID) shortly followed by surgery. From these 250 patients are fully assessable. The median GD of 5 days was used as a discriminator. The median follow-up for all patients was 39 months. GD > 5 days was a significant discriminator for actuarial 5-years OS (69% vs 47%, p = 0.002), CSS (82% vs 57%, p = 0.0007), DFS (62% vs 41%, p = 0.0003) but not for LC (93% vs 90%, p = non-significant). In multivariate analysis, the following factors independently predict outcome; for OS: age, GD, circumferential margin (CM) and nodal stage (ypN); for CSS: GD, ypN and vascular invasion (VI); for DFS: CEA, distance to anal verge, GD, ypN and VI; for LC: CM only. Gap duration predicts survival outcome but not local control. The patients submitted to surgery after a median delay of more than 5 days had a significantly better outcome. [less ▲]

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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 detailCPT-11 and concomitant hyperfractionated accelerated radiotherapy induce efficient local control in rectal cancer patients: results from a phase II
Voelter, V; Zouhair, A; Vuilleumier, H et al

in British Journal of Cancer (2006), 95

Patients with rectal cancer are at high risk of disease recurrence despite neoadjuvant radiochemotherapy with 5-Fluorouracil (5FU), a <br />regimen that is now widely applied. In order to develop a ... [more ▼]

Patients with rectal cancer are at high risk of disease recurrence despite neoadjuvant radiochemotherapy with 5-Fluorouracil (5FU), a <br />regimen that is now widely applied. In order to develop a regimen with increased antitumour activity, we previously established the <br />recommended dose of neoadjuvant CPT-11 (three times weekly 90 mgm 2) concomitant to hyperfractionated accelerated <br />radiotherapy (HART) followed by surgery within 1 week. Thirty-three patients (20 men) with a locally advanced adenocarcinoma of <br />the rectum were enrolled in this prospective phase II trial (1 cT2, 29 cT3, 3 cT4 and 21 cNþ). Median age was 60 years (range 43– <br />75 years). All patients received all three injections of CPT-11 and all but two patients completed radiotherapy as planned. Surgery <br />with total mesorectal excision (TME) was performed within 1 week (range 2–15 days). The preoperative chemoradiotherapy was <br />overall well tolerated, 24% of the patients experienced grade 3 diarrhoea that was easily manageable. At a median follow-up of 2 <br />years no local recurrence occurred, however, nine patients developed distant metastases. The 2-year disease-free survival was 66% <br />(95% confidence interval 0.48–0.83). Neoadjuvant CPT-11 and HART allow for excellent local control; however, distant relapse <br />remains a concern in this patient population. [less ▲]

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

in Radiotherapy & Oncology (2005)

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 ... [more ▼]

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 distance=5 cm). The pattern of failure is dominated by distant metastases and treatment intensification will obviously require a systemic approach. [less ▲]

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See detailRepeated beta irradiation for recurrent coronary in-stent restenosis.
Eeckhout, E; Roguelov, C; Berger, A et al

in Heart (2005), 91

Vascular brachytherapy (VBT) is the only proven treatment option for patients with in-stent restenosis. In seven randomised trials with almost 1500 patients that evaluated {gamma} (five studies) and ß ... [more ▼]

Vascular brachytherapy (VBT) is the only proven treatment option for patients with in-stent restenosis. In seven randomised trials with almost 1500 patients that evaluated {gamma} (five studies) and ß (two trials) irradiation, target vessel failure reduction ranged from 73% to 34% by VBT compared with conventional angioplasty.1 However, the reported restenosis rates with the active treatment still varied between 17% and 32%.1 We therefore postulated that repeat VBT is safe and efficacious for preventing refractory in-stent restenosis in high risk patients with failed VBT. METHODS Beginning in January 1999, VBT was applied for all patients with in-stent restenosis. VBT was systematically performed with intravascular ultrasound (IVUS) guidance. The repeat procedure was performed with a strontium/yttrium-90 source train (BetaCath, Novoste, Norcross, Georgia, USA). The design and application of this catheter have been described previously.2 The dosimetry was based on the manufacturer’s recommendations but taking into account not the angiographic vessel reference diameter but the external elastic membrane diameter (as determined by IVUS). The mean dose delivered at 2 mm from the source centre was 23.3 (2.2) Gy during the index procedure and 25.3 (2.2) Gy during the repeat intervention. Percutaneous coronary intervention (PCI) was performed according to standard clinical practice. Failed VBT was defined as angina recurrence combined with target vessel failure (as documented by any repeat angiography: premature depending on early symptom recurrence or at the planned six month control). Repeat VBT was considered for patients estimated to be at high risk for refractory in-stent restenosis or if they had a prognostic risk—that is, diffuse or ostial in-stent restenosis or total occlusion, or proximal left anterior descending artery stenosis. Focal edge effect stenoses and non-prognostic lesion locations in symptomatic patients were treated by conventional PCI. Written informed consent was obtained from all patients before intervention. The study was approved by the hospital ethics committee. All VBT patients were prospectively entered in a dedicated database by a person not taking part in the interventions. A combined antiplatelet treatment (aspirin 100 mg and clopidogrel 75 mg daily) was prescribed for at least six months after the index procedure and for one year after the second VBT. Control angiography was mandatory at six months in all VBT patients and systematic long term clinical follow up was carried out. RESULTS Between July 1998 and March 2003, 251 VBT interventions were performed at our institution: 22 patients were treated for primary restenosis prevention and 229 patients for in-stent restenosis. VBT failed in 34 patients (14.8%): 23 underwent conventional PCI and 11 underwent repeat VBT. The baseline clinical and angiographic demographics were comparable for both groups. Concerning the repeat VBT group, mean (SD) age was 60 (7) years, nine patients were men, and two had diabetes. All patients who underwent a repeat procedure had incapacitating angina pectoris. Angina recurred at 7 (2) months (range 4–10) after the first, failed VBT. The restenosis pattern (table 1Go) was diffuse in the majority of patients at the first presentation and remained diffuse with exacerbation to total occlusion in two patients. In the focal restenosis group, two patients had ostial in-stent restenosis. The cause of recurrent in-stent restenosis was an evident geographical miss in two patients (a focal and a diffuse pattern case). IVUS and angioplasty were successful before irradiation therapy in all patients. During repeat VBT, a 40 mm source train was used in seven patients and a pullback technique was required in two because of the length of the restenotic segment. No additional stents were implanted and no evidence of geographical miss was seen at repeat intervention. Table 1Go shows quantitative coronary angiography and IVUS data. During the index procedure, the minimum in-stent luminal area increased from mean (SD) 5.8 (1.8) to 7.5 (1.4) mm2. This area was maintained at the repeat intervention at 7.8 (2.1) mm2 and further expanded to 8.9 (1.8) mm2. All repeat interventions were technically successful and there were no adverse clinical events during the in-hospital phase. [less ▲]

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See detailA pilot study of silicone tissue expander prosthesis to protect the small bowel during radiation therapy for uterine malignancies
Zouhair, Abderrahim; Delaloye, J-F; Oszahin, Mahmut et al

in Turkish Journal of Cancer (2004), 34(1), 11-18

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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 detailLa gynécomastie sous antiandrogènes : un mal inéluctable? la radiothérapie : une solution simple et efficace!
Coucke, Philippe ULg; JICHLISKI; MATZINGER et al

in Revue Médicale de la Suisse Romande (2004), 124(1), 51-54

La gynécomastie secondaire au traitement par anti-androgènes, est une complication fréquente des traitements hormonaux utilisés pour les patients souffrant de cancer prostatique. Cette gynécomastie est le ... [more ▼]

La gynécomastie secondaire au traitement par anti-androgènes, est une complication fréquente des traitements hormonaux utilisés pour les patients souffrant de cancer prostatique. Cette gynécomastie est le résultat d'un déséquilibre hormonal entre les oestrogènes et les androgènes. On peut raisonnablement estimer que l'incidence de cette gynécomastie va augmenter compte tenu de l'effet bénéfique de la manipulation hormonale sur le devenir des patients atteints d'un cancer de la prostate. La gynécomastie, souvent associée à la mastodynie, a un effet délétère sur la qualité de vie. Si la chirurgie est une option thérapeutique pour les formes installées et irréversible, caractérisée par une composante de hyalinisation et fibrose dominant le tableau histologique, la radiothérapie reste le traitement de choix pour les formes précoces, voire même à titre prophylactique dans les groupes de patients à haut risque. C'est un traitement simple et efficace, peu toxique et bénéfique en qualité de vie et ceci a été confirmé par des essais randomisés. L'approche médicamenteuse n'a pas encore démontré son efficacité ni son innocuité et de toute façon aucune substance médicamenteuse n'a été enregistrée pour cette indication. [less ▲]

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See detailClinical outcome following combination of cutting balloon angioplasty and coronary β-radiation for in-stent restenosis: A report from the RENO registry
Coucke, Philippe ULg; Roguelov; Eeckhout

in Journal of Invasive Cardiology (The) (2003), 15(12), 706-709

At present, vascular brachytherapy is the only efficient therapy for in-stent restenosis. Nevertheless, edge restenosis often related to geographical miss has been identified as a major limitation of the ... [more ▼]

At present, vascular brachytherapy is the only efficient therapy for in-stent restenosis. Nevertheless, edge restenosis often related to geographical miss has been identified as a major limitation of the technique. The non-slippery cutting balloon has the potential to limit vascular barotraumas, which, together with low-dose irradiation at both ends of the radioactive source, are the prerequisite for geographical miss. This prospective study aimed to examine the efficacy of combining cutting balloon angioplasty and brachytherapy for in-stent restenosis. The Radiation in Europe NOvoste (RENO) registry prospectively tracked all patients who had been treated by coronary β-radiation with the Beta-Cath System (Novoste Corporation, Brussels, Belgium) but were not included in a randomized radiation trial. A subgroup of patients with in-stent restenosis treated by cutting balloon angioplasty and coronary β-radiation (group 1, n = 166) was prospectively defined, and clinical outcomes of patients at 6 months were compared with those of patients treated by conventional angioplasty and coronary β-radiation (group 2, n = 712). At 6-month follow-up, there was a significant difference between groups 1 and 2 in target vessel revascularization (10.2% versus 16.6% respectively; p = 0.04) and in the incidence of major adverse clinical events (MACE) including death, myocardial infarction, and revascularization (10.8% versus 19.2%; p = 0.01). This observation was confirmed by a multivariate analysis indicating a lower risk for MACE at 6 months (odds ratio: 0.49; confidence intervals: 0.27-0.88; p = 0.02). Compared to conventional angioplasty, cutting balloon angioplasty prior to coronary beta-radiation with the Beta-Cath System seems to improve the 6-month clinical outcome in patients with in-stent restenosis. [less ▲]

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See detailChanger l’organisation du « système » TRM* en radio-oncologie par l’introduction d’un apprentissage organisationnel pour faciliter la mise en place des progrès technologiques.
COUCKE, Philippe ULg

Master of advanced studies dissertation (2003)

Le service de radio-oncologie est caractérisé par la technicité et la complexité toujours en évolution de la prise en charge thérapeutique. Le développement dans ce domaine est tel que le service de radio ... [more ▼]

Le service de radio-oncologie est caractérisé par la technicité et la complexité toujours en évolution de la prise en charge thérapeutique. Le développement dans ce domaine est tel que le service de radio-oncologie risque très rapidement d’être déphasé par rapport à la qualité de la prise en charge que le patient est en mesure d’attendre dans les limites des ressources disponibles. Si l’organisation n’est pas apte à prendre en compte la nécessité d’une amélioration continue, nous ne serons plus capables d’assurer des soins de haute qualité auquel le patient a droit, et nous perdrons rapidement l’habilité technique dans la pratique des soins. Afin d’assurer la maîtrise et la pérennité d’une prise en charge de haute qualité nous voulons mettre en route une démarche globale d’amélioration continue qui doit finalement aboutir à une démarche de projet de qualité et de certification. Nous faisons le constat, aujourd’hui, que le groupe des techniciens en radiologie médicale* ne répond pas aux critères d’une organisation apprenante qui est une condition sine qua non pour l’amélioration continue. Afin de modifier cette situation, il nous faut définir un facteur suffisamment puissant pour déclencher cet évolution d’état d’esprit. Ce changement sera abordé par la mise en place d’une mesure de satisfaction au sein même du système TRM en collaboration avec la cellule ESOP de l’Institut Universitaire de Médecine sociale et Préventive (IUMSP). Cette démarche basée sur un « brainstorming » dont la trame de réflexion pourrait être l’évaluation du niveau atteint dans la pyramide de satisfaction de Maslow par les TRM (analyse interne du système). Ce genre d’exercice effectué par les TRM pourrait aboutir à une visualisation structurée de la problématique du manque d’amélioration continue et des causes de l’absence d’une telle organisation apprenante en utilisant la technique du diagramme d’Ishikawa. L’avantage de cette démarche, c’est que le groupe TRM en tant que tel va aboutir à l’élaboration active d’un certain nombre d’idées clés censées amener une solution aux problèmes énoncés. En même temps nous voulons déclencher une redéfinition de la vision d’entreprise et des tâches et des compétences requises (une formulation claire des exigences en termes qualitatifs et quantitatifs de l’attente du service vis-à-vis des TRM) ; cette tâche incombe aux mandataires du changement c’est-à-dire les médecins et le groupe des physiciens qui font partie de l’environnement immédiat du système TRM, et qui ont besoin d’une amélioration continue du savoir (savoir, savoir être et savoir faire) des TRM afin de pouvoir implémenter des nouvelles techniques complexes en radio-oncologie. Cette « analyse externe » va permettre de définir des objectifs clairs et une vision commune. Le constat de la différence entre l’analyse externe et interne doit aboutir à un travail de groupe mixte (TRM et mandataires) afin de déboucher sur une concordance des deux visions. Afin de faire participer les TRM à l’élaboration des idées-clés des solutions, la mise en place desdites solutions et l’évaluation de l’efficacité des solutions mises en place, nous prévoyons de créer différents groupes de travail ayant chacun un objectif clair et précis (exemple : mise en place de l’utilisation en routine de l’imagerie portale pour le contrôle de qualité systématique des champs d’irradiation). Cette démarche va provoquer un changement fondamental dans le système TRM, une évolution d’une organisation primaire vers une organisation secondaire travaillant par objectifs, plus apte à s’adapter aux exigences de l’environnement, capable d’anticiper et non pas de subir les mises à jour technologiques. Par la même occasion, cette démarche une fois amorcée va obliger l’intégralité du service de radio-oncologie à établir un référentiel d’auto-évaluation et un guide des procédures qui vont permettre à terme d’aboutir sur une certification ISO 9001-2000. *Le genre masculin du titre professionnel s’entend bien entendu également au féminin. [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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See detailPreoperative hyperfractionated acclerated radiotherapy (HART) and concomittant CPT-11 in advanced rectal carcinoma. A phase I study.
Voelter, V; Stupp, R; Matter, M et al

in International Journal of Radiation, Oncology, Biology, Physics (2003), 56(5), 1288-1294

Purpose: Patients with locally advanced rectal carcinoma are at risk for both local recurrence and distant metastases. We demonstrated the efficacy of preoperative hyperfractionated accelerated ... [more ▼]

Purpose: Patients with locally advanced rectal carcinoma are at risk for both local recurrence and distant metastases. We demonstrated the efficacy of preoperative hyperfractionated accelerated radiotherapy (HART). In this Phase I trial, we aimed at introducing chemotherapy early in the treatment course with both intrinsic antitumor activity and a radiosensitizer effect. Methods and Materials: Twenty-eight patients (19 males; median age 63, range 28–75) with advanced rectal carcinoma (cT3: 24; cT4: 4; cN : 12; M1: 5) were enrolled, including 8 patients treated at the maximally tolerated dose. Escalating doses of CPT-11 (30–105 mg/m2/week) were given on Days 1, 8, and 15, and concomitant HART (41.6 Gy, 1.6 Gy bid 13 days) started on Day 8. Surgery was to be performed within 1 week after the end of radiochemotherapy. Results: Twenty-six patients completed all preoperative radiochemotherapy as scheduled; all patients underwent surgery. Dose-limiting toxicity was diarrhea Grade 3 occurring at dose level 6 (105 mg/m2). Hematotoxicity was mild, with only 1 patient experiencing Grade 3 neutropenia. Postoperative complications (30 days) occurred in 7 patients, with an anastomotic leak rate of 22%. Conclusions: The recommended Phase II dose of CPT-11 in this setting is 90 mg/m2/week. Further Phase II exploration at this dose is warranted. © 2003 Elsevier Inc. [less ▲]

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