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See detailTiming effect of combined radioimmunotherapy and radiotherapy on a human solid tumor in nude mice.
Coucke, Philippe ULg; Lin-Quan, Sun; Vogel, Charles-André et al

in Cancer Research (1997), 57

Timing effects of radioimmunotherapy (HIT) combined with external beam radiotherapy (RT) were assessed In human colon carcinoma xe nografts. Initially, dose effects offractlonated RT and RIT were ... [more ▼]

Timing effects of radioimmunotherapy (HIT) combined with external beam radiotherapy (RT) were assessed In human colon carcinoma xe nografts. Initially, dose effects offractlonated RT and RIT were evaluated separately. Then, 30 Gy RT (10 fractions over 12 days) were combined with three weekly Lv. injections of 200 g@Ci of 131I-labeled anti-carcino embryonic antigen monoclonal antibodies in four different treatment schedules. RIT was given either prior to, concurrently, Immediately after, or 2 weeks after RT administration. The longest regrowth delay (RD) of 105 days was observed in mice treated by concurrent administration of RT and lilT, whereas the RDs of RT and RIT alone were 34 and 20 days, respectively. The three sequential combination treatments produced sig nificantly shorter RDs ranging from 62 to 70 days. The tumor response represented by the minimal volume (MV) also showed that concurrent administration of RT and RIT gave the best result, with a mean MV of 4.5% as compared to MVs from 26 to 53% for the three sequential treatments. The results were confirmed In a second experiment, In which a RT of 40 Gy was combined with an identical lilT as above (three injections of 200 g&Ci of ‘31I-labeled monoclonal antibodies). At compa rable toxicity levels, the maximum tolerated RT or BIT alone gave shorter RDs and less tumor shrinkage compared to slinultaneous RT+RIT. These results may be useful for designing clinical protocols ofcombined RIT and RT. [less ▲]

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See detailPrimary radiation therapy or surgery combined or not to radiation therapy in the management of squamous cell carcinoma of the penis
Zouhair, Abderrahim; Ozsahin, Mahmut; Douglas, Pelham et al

in International Journal of Radiation, Oncology, Biology, Physics (1997), 39(2 (Supplément)), 295

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See detailAlteration of radiation response in vitro by simultaneous modulation of the de novo and salvage pathways to deoxynucleoside triphosphate pool by (E)-2′-Deoxy-(Fluoromethylene)cytidine and thymidine analogs
Coucke, Philippe ULg; Li, Ye-Xiong; Cottin, Eliane et al

in International Journal of Radiation, Oncology, Biology, Physics (1997), 39(2 (supp1)), 257

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See detailClinical characteristics, prognosis and treatment for pelvic cryptorchid seminoma
Li; COUCKE, Philippe ULg; Qian et al

in International Journal of Radiation, Oncology, Biology, Physics (1997), 38(2), 351-357

Purpose: To analyze the clinical characteristics, prognosis, and treatment outcome of pelvic cryptorchid seminoma (PCS), and to determine whether whole abdominal-pelvic irradiation for Stage I disease is ... [more ▼]

Purpose: To analyze the clinical characteristics, prognosis, and treatment outcome of pelvic cryptorchid seminoma (PCS), and to determine whether whole abdominal-pelvic irradiation for Stage I disease is necessary. Methods and Materials: From 1958 to 1991,60 patients with PCS were treated at the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing. They presented with a lower abdominal mass and showed a predominance for the right side. A high proportion of patients with PCS [ 26 of 60 (43% )] had metastatic disease, compared to 20% of those with scrotal seminoma, and there was a tendency toward a higher frequency of pelvic nodal metastases. There were 34 Stage I, 6 Stage IIA, 11 Stage IIB, 5 Stage III, and 4 Stage IV patients. Of these 60 patients, 56 underwent laparotomy with or without cryptorchiectomy (37 radical orchiectomy, 7 partial orchiectomy, and 12 biopsy of the primary or cervical node), and 4 cervical node biopsy only. All patients were further treated with radiotherapy, chemotherapy, or a combination of both. Patients with Stage I and II disease received radiotherapy, whereas patients with Stage III and IV were treated with chemotherapy. Results: The overall and disease-free survivals at 5 and 10 years were 92% and 87%, and 88% and 84%, respectively. The 5- and lo-year survivals were 100% for Stage I, 94% and 87% for Stage II, and 56% and 42% for Stage III/IV, respectively @ < 0.05). Volume of irradiation, i.e., whole abdominal-pelvic radiotherapy ( 10 patients), versus hockey-stick encompassing paraaortic, ipsilateral iliac nodes and the primary tumor or tumor bed (17) did not influence outcome in Stage I patients. Five patients relapsed within 2-12 years after treatment, and four of these patients were successfully salvaged. Four patients developed a second malignant tumor and died. Conclusion: Stage I and II PCS can he adequately controlled by radiotherapy regardless of the surgical procedure. Whole abdominal-pelvic irradiation for Stage I and IIA disease is not required, and fields can be limited to the paraaortic, ipsilateral iliac nodes and primary tumor or tumor bed. We recommend platinum-based chemotherapy for Stage IIB-IV PCS. 0 1997 Elsevier Science Inc. [less ▲]

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See detailPrognostic factors in urothelial renal pelvis and ureter tumors: A multicenter Rare Cancer Network study
Ozsahin, Mahmut; Zouhair, Abderrahim; Villà, S. et al

in International Journal of Radiation, Oncology, Biology, Physics (1997), 3(2(supp)), 290

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See detailAntitumor and radiosensitizing effects of (E)-2'-Deoxy-2'-(Fluoromethylene) cytidine, a novel inhibior of ribonucleotide diphosphate reductase on human colon carcinoma xenografts in nude mice.
Sun, Lin-Quan; Li, Ye-Xiong; Guillou, Louis et al

in Cancer Research (1997), 57

Antitumor and radiosensitizing effects of (E).2'-deoxy.2'-(fluromethyl ene) cytidine (FMdC), a novel inhibitor of ribonucleotide reductase, were evaluated on nude mice bearing s.c. xenografts and liver ... [more ▼]

Antitumor and radiosensitizing effects of (E).2'-deoxy.2'-(fluromethyl ene) cytidine (FMdC), a novel inhibitor of ribonucleotide reductase, were evaluated on nude mice bearing s.c. xenografts and liver metastases of a human colon carcinoma. FMdC given once daily or twice weekly has a dose-dependent antitumor effect. The maximum tolerated dose In the mice was reached with 10 mgi'kg applied daily over 12 days. Twice weekly administration of FMdC reduced its toxicity but lowered the antitumor effect. Treatment of preestablished liver micrometastases obtained via intrasplenic injection of tumor cells, with 5 or 10 mgfkg FMdC, signifi candy prolonged the survival of the mice as compared to controls (P < 0.025 and P < 0.001, respectively). Ten mg/kg resulted in longer survival than S mg/kg FMdC (P < 0.05). Radiotherapy alone of s.c. xenografts (10 fractions over 12 days) yielded the radiation dose required to produce local tumor control in 50% of the treated mice (TCD@O)of 43.0 Gy. When combined with FMdC, TCDsawas reduced to 22.5 and 19.0 Gy at doses of 5 and 10 mg/kg given i.p. 1 h before each irradiation, respec tively. The corresponding enhancement ratios were 1.91 and 2.43, respec lively. FMdC produced moderate and reversible myelosuppression. When 5 mg/kg FMdC was combined with irradiation, there was no increased skin or hematological toxicity as compared to radiotherapy or FMdC alone. At the 10 mg/kg level, however, lower leukocyte counts were observed. These results show that FMdC appears to be a potent anticancer drug and radiosensitizer [less ▲]

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See detailRadiotherapie externe focalisee apres resection de metastase cerebrale unique: etude prospective de phase I-II
Zouhair; COUCKE, Philippe ULg; Douglas, Pelham et al

in Bulletin du Cancer. Radiothérapie : Journal de la Société Française du Cancer : Organe de la Société Française de Radiothérapie Oncologique (1997), 1

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See detailCell-line specific radiosensitizing effect of zalcitabine (DDC)
Coucke, Philippe ULg; Li, Ye-Xiong; Copaceanu, Marie-Laure et al

in Acta Oncologica (1997)

The potential of zalcitabine (ddC) to act as an ionizing radiation response modifier was tested on exponentially growing human cancer cells in vitro. Two human cell lines, WiDr (colon) and MCF-7 (breast ... [more ▼]

The potential of zalcitabine (ddC) to act as an ionizing radiation response modifier was tested on exponentially growing human cancer cells in vitro. Two human cell lines, WiDr (colon) and MCF-7 (breast) were exposed to ddC at 10 p M concentration for various lengths of tide (18, 24, 48 and 72 h). On the WiDr cell line the dual effect of concentration and duration of exposure prior to irradiation was investigated. Experimental endpoints were clonogenicity and viability, as measured by colony formation assay (CFA) and MTT assay respectively. The impact on cell-cycle distribution prior to irradiation was assessed by flow cytometry using a double labeling technique (propidium iodide and bromodeoxyuridine pulse label). A significant reduction in surviving fraction and viability was observed for WiDr-cells irradiated after pre-exposure to 10 pM for 18, 48 and 72 h as compared to corresponding irradiated controls. At lower concentrations (1 and 5 pM), the radiosensitizing effect was only significant after a 72-h exposure (assessed by CFA). For MCF-7, ddC induced a significant modification of the dose response only with 24 and 48 h preincubation. However, the overall effect was less pronounced as compared to WiDr. Cell-cycle analysis showed accumulation in S-phase, 48 and 72 h after treatment with 10 pM ddC in the WiDr cells, with a progressive shift to late S-phase as shown by the biparametric analysis. The degree of radiosensitization is cell-line dependent with the most important sensitization observed on the most <<radioresistant cell line>>, ix., the cell line with the lowest alpha value and highest SF 2 (WiDr). For WiDr, radiosensitization by ddC depends on the duration of exposure and the concentration of the drug. Received 29 February 1996 Accepted 10 December 1996 [less ▲]

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See detailNew ribonucleotide reductase inhibitor, (E)-2′-deoxy-(fluromethylene) cytidine, acts as a radiosensitizer on human colon and cervix cancer cell lines
Coucke, Philippe ULg; LI, XY; Cottin, E et al

in Radiotherapy & Oncology (1996), 40(Supplément 1), 135

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See detailPotential doubling time determination in a multicentre clinical study.
COUCKE, Philippe ULg

in Abstract book (1996)

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See detailEffect of total treatment time on event-free survival in carcinoma of the cervix
Delaloye, J-F; COUCKE, Philippe ULg; Pampallona, S et al

in Gynecologic Oncology (1996), 60

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See detailYounger age as a bad prognostic factor in patients with carcinoma of the cervix.
Delaloye, J-F; Pampallona, S; COUCKE, Philippe ULg et al

in European Journal of Obstetrics & Gynecology & Reproductive Biology (1996)

Objective: To verify the influence of age on the prognosis of cervix carcinoma. Study design: Five hundred and sixty eight patients treated for a FIGO stage IB-IVA with radical irradiation in the Centre ... [more ▼]

Objective: To verify the influence of age on the prognosis of cervix carcinoma. Study design: Five hundred and sixty eight patients treated for a FIGO stage IB-IVA with radical irradiation in the Centre Hospitalier Universitaire Vaudois of Lausanne were subdivided according to the following age categories: _<45, 46-60, 61-69 and > 70 years. Taking the 46-60 years age group as the reference, the hazard ratios (HR) of death and corresponding 95% confidence intervals (95% CI) were estimated by means of a Cox multivariate analysis. Results: The 5-year survival rates were, respectively, 57%, 67%, 60% and 45%. For the youngest women the risk of death was significantly increased (HR = 2.00, 95% CI [1.32-3.00]) and was even more accentuated in advanced stages. Conclusion: Age under 45 years is a bad prognostic factor in carcinoma of the cervix. [less ▲]

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See detailWhat about lorisk Figo Stage Ia and Ib, G1-G2 endometrial adenocarcinoma ?
Delaloye, J-F; Megalo; COUCKE, Philippe ULg et al

in Radiotherapy & Oncology (1996), 43(Supp 1), 6

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See detailRadiosensitization in vitro by (E)-2′-(fluoromethylene)-deoxy-cytidine (FMdC), pentoxifylline (PTX) or a combination
Li; COUCKE, Philippe ULg; Paschoud et al

in International Journal of Radiation, Oncology, Biology, Physics (1996), 36(1 (supp1)), 383

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See detailMort mitotique ou mort apoptotique par irradiation : Même combat ?
Coucke, Philippe ULg; ZOUHAIR

in Médecine et Hygiène (1996), 54(2121), 1241-1245

La mort cellulaire active (apoptose) est un phénomène ubiquitaire dans les organismes multicellulaires. L'apoptose joue un rôle essentiel dans la genèse d'un cancer et dans la réponse au traitement ... [more ▼]

La mort cellulaire active (apoptose) est un phénomène ubiquitaire dans les organismes multicellulaires. L'apoptose joue un rôle essentiel dans la genèse d'un cancer et dans la réponse au traitement oncologique. Les radiations ionisantes sont capables d'induire une mort mitotique et une mort apoptotique. Nous définissons les caractéristiques radiobiologiques de chaque type de mort cellulaire et situons l'importance de l'apoptose pour la réponse tumorale aux radiations ionisantes. La modulation de ce «suicide cellulaire» devrait permettre une amélioration de l'index thérapeutique mais ceci implique une connaissance approfondie des mécanismes qui règlent l'apoptose [less ▲]

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See detailDoes proliferation status predict radiation response in human tumors?
Coucke, Philippe ULg

in Radiotherapy & Oncology (1996), 40(Supp 1), 55

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See detailT92-0045: Interlaboratory quality control on Tpot measurements
Coucke, Philippe ULg; Beer, K.; Bernier, J. et al

in International Journal of Radiation, Oncology, Biology, Physics (1996), 36(1(supp1)), 384

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See detailChemical Modifiers of Cancer Treatment
Coucke, Philippe ULg; Workman, Paul; Coleman, Norman

in Chemical Modifiers of Cancer Treatment (1995, August 22)

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See detailThe rationale to switch from postoperative hyperfractionated accelerated radiotherapy to preoperative hyperfractionated accelerated radiotherapy in rectal cancer
COUCKE, Philippe ULg; Sartirelli, Britta; Cuttat, Jean-François et al

in International Journal of Radiation, Oncology, Biology, Physics (1995), 32(1), 181-188

Purpose: To demonstrate the feasibility of preoperative Hyperfractionated Accelerated RadioTherapy (preop-HART) in rectal cancer and to explain the rationales to switch from postoperative HART to ... [more ▼]

Purpose: To demonstrate the feasibility of preoperative Hyperfractionated Accelerated RadioTherapy (preop-HART) in rectal cancer and to explain the rationales to switch from postoperative HART to preoperative HART. Methods and Materials: Fifty-two consecutive patients were introduced in successive Phase I trials since 1989. In trial 89-01, postoperative HART (48 Gy in 3 weeks) was applied in 20 patients. In nine patients with locally advanced rectal cancer, considered unresectable by the surgeon, 32 Gy in 2 weeks was applied prior to surgery (trial 89-02). Since 1991, 41.6 Gy in 2.5 weeks has been applied preoperatively to 23 patients with T3-T4 any N rectal cancer immediately followed by surgery (trial 91-01). All patients were irradiated at the department of radiation-oncology with a four-field box technique (1.6 Gy twice a day and with at least a 6-h interval between fractions). The minimal accelerating potential was 6 MV. Acute toxicity was scored according to the World Health Organization (WHO for skin and small bowel) and the Radiation Therapy Oncology Group criteria (RTOG for bladder). This was done weekly during treatment and every 3 months thereafter. Small bowel volume was estimated by a modified 'Gallagher's' method. Results: Acute toxicity was acceptable both in postoperative and preoperative setup. The mean acute toxicity was significantly lower in trial 91-01 compared to 89-01. This difference was due to the smaller amount of small bowel in irradiation field and lower total dose in trial 91-01. Moreover, there was a significantly reduced delay between surgery and radiotherapy favoring trial 91-01 (median delay 4 days compared to 46 days in trial 89-01). Nearly all patients in trial 89-02 and 91-01 underwent surgery (31 out of 32; 97%). Resection margins were negative in 29 out of 32. Hospitalization duration in trial 91- 01 was not significantly different from trial 89-01 (19 vs. 21 days, respectively). Conclusions: Hyperfractionated accelerated radiotherapy immediately followed by surgery is feasible as far as acute toxicity is concerned. Preoperative HART is favored by a significantly lower acute toxicity related, in part, to a smaller amount of irradiated small bowel, and a shorter duration of the delay between radiotherapy and surgery. Moreover, the hospital stay after preoperative HART is not significantly increased. [less ▲]

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