L. Buffat - Academia.edu (original) (raw)
Papers by L. Buffat
Hepatology 26(4 Part, Apr 26, 1997
Afin d'evaluer les possibilites de traitement conservateur mammaire et l'evolution de pat... more Afin d'evaluer les possibilites de traitement conservateur mammaire et l'evolution de patientes atteintes d'un cancer du sein localement avance (CSLA) non inflammatoire et stade II de plus de 3 cm de diametre apres une chimiotherapie premiere (CT) suivie d'une irradiation externe pre-operatoire (RT), nous avons revu 147 patientes traitees de 1982 a 1990, avec une mediane de recul depuis le debut de traitement de 94 mois. Le traitement d'induction comprenait 4 cycles de CT (doxorubicine, vincristine, 5-fluorouracile, cyclophosphamide), suivis d'une radiotherapie pre-operatoire (45 Gy en 4,5 semaines dans le sein et les aires ganglionnaires homolaterales) et d'un cinquieme cycle de CT. Trois approches therapeutiques loco-regionales etaient proposees en fonction de la reponse tumorale. Pour 52 patientes (35 %) avec une tumeur residuelle de plus de 3 cm de diametre, ou retro-areolaire, ou plurifocale, une mastectomie avec curage axillaire a ete realisee. Quat...
Journal of Experimental Medicine, 2014
Trail+DX5−Eomes− natural killer (NK) cells arise in the mouse fetal liver and persist in the adul... more Trail+DX5−Eomes− natural killer (NK) cells arise in the mouse fetal liver and persist in the adult liver. Their relationships with Trail−DX5+ NK cells remain controversial. We generated a novel Eomes-GFP reporter murine model to address this question. We found that Eomes− NK cells are not precursors of classical Eomes+ NK cells but rather constitute a distinct lineage of innate lymphoid cells. Eomes− NK cells are strictly dependent on both T-bet and IL-15, similarly to NKT cells. We observed that, in the liver, expression of T-bet in progenitors represses Eomes expression and the development of Eomes+ NK cells. Reciprocally, the bone marrow (BM) microenvironment restricts T-bet expression in developing NK cells. Ectopic expression of T-bet forces the development of Eomes− NK cells, demonstrating that repression of T-bet is essential for the development of Eomes+ NK cells. Gene profile analyses show that Eomes− NK cells share part of their transcriptional program with NKT cells, incl...
The Journal of experimental medicine, Jan 26, 2015
Natural killer (NK) cell maturation is a tightly controlled process that endows NK cells with fun... more Natural killer (NK) cell maturation is a tightly controlled process that endows NK cells with functional competence and the capacity to recognize target cells. Here, we found that the transcription factor (TF) Zeb2 was the most highly induced TF during NK cell maturation. Zeb2 is known to control epithelial to mesenchymal transition, but its role in immune cells is mostly undefined. Targeted deletion of Zeb2 resulted in impaired NK cell maturation, survival, and exit from the bone marrow. NK cell function was preserved, but mice lacking Zeb2 in NK cells were more susceptible to B16 melanoma lung metastases. Reciprocally, ectopic expression of Zeb2 resulted in a higher frequency of mature NK cells in all organs. Moreover, the immature phenotype of Zeb2(-/-) NK cells closely resembled that of Tbx21(-/-) NK cells. This was caused by both a dependence of Zeb2 expression on T-bet and a probable cooperation of these factors in gene regulation. Transgenic expression of Zeb2 in Tbx21(-/-) N...
Cancer/Radiothérapie, 1998
Cancer radiothérapie : journal de la Société française de radiothérapie oncologique, 2001
To identify prognostic factors and treatment toxicity in a series of operable endometrial adenoca... more To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. Between November 1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged according to the 1988 FIGO staging system, underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph node dissection. The chronology of RT was not randomized and depended on the usual practices of the surgical teams. Group I: 79 pts received preoperative uterovaginal brachytherapy (mean total dose [MD]: 57 Gy). Group II: 358 pts received postoperative RT (196 pts received vaginal brachytherapy alone [MD: 50 Gy], 158 pts had external beam pelvis RT [EPRT] [MD: 46 Gy over 5 weeks] followed by vaginal brachytherapy [MD: 17 Gy], and 4 pts had EPRT alone [MD: 46 Gy over 5 weeks]). The mean follow-up was 128 months. The 10-year disease-free survival rate was 86%. From 57 recurrences, 12 were isolated locoregionally. Multivaria...
Cancer radiothérapie : journal de la Société française de radiothérapie oncologique
Retrospective study to analyze the results of external beam radiation treatment with or without s... more Retrospective study to analyze the results of external beam radiation treatment with or without surgery for loco-regional recurrence of adenocarcinoma of the rectum following previous surgery without pre- or post-operative radiotherapy. Between March 1973 and November 1991, 211 patients with loco-regional recurrence of rectum cancer were treated with external beam radiation treatment. Radical surgery was the only initial treatment modality. Surgical resection of local recurrence was done in 36 patients and only 17 patients could undergo complete resection. Forty-seven patients underwent radiotherapy (RT) combined with surgery and 164 received external beam radiation treatment alone to a mean total dose of 46 Gy. Among the 151 patients whose recurrence was revealed by pain, 64 (42%) were considered to have a complete symptomatic response after loco-regional treatment with radiosurgery or RT alone. The mean duration of response was 12 months. The 3-year overall survival rate was 16%. ...
Bulletin du cancer. Radiothérapie : journal de la Société française du cancer : organe de la société française de radiothérapie oncologique, 1995
From 1977 to 1988, 120 consecutive patients with a diagnosis of low-grade astrocytoma were referr... more From 1977 to 1988, 120 consecutive patients with a diagnosis of low-grade astrocytoma were referred to our department for radiotherapy. Fourty-one patients (group 1) underwent surgery and post operative external radiation therapy (2 gross total resections and 39 subtotal resections). Sixty-nine patients underwent exclusive external radiotherapy (group 2). In ten patients, the irradiation was delivered by stereotactic implantation of iridium-192 wires into the tumor with or without external irradiation (group 3). Ten had pilocytic astrocytomas (mean age, 24 years) and twenty had microcystic astrocytomas (mean age, 35.4 years). The 5- and 10-year survival rates were 55.6% and 44.4%, respectively and 55% and 48%. Ninety astrocytomas were classified as "ordinary" astrocytoma (mean age, 36.8 years). The 5- and 10-year overall survival rates were 51% and 20.5%, respectively. The same probabilities at 5 and 10 years were 65% and 37% respectively, for group 1, 38.8% and 12.7% for ...
Journal of molecular graphics, 1994
The representation and display of protein surfaces are useful in many areas of molecular modeling... more The representation and display of protein surfaces are useful in many areas of molecular modeling, and surface shape study is particularly important in the analysis of protein-ligand interactions. We introduce here the notion of the molecular surface convex hull, allowing the depth of any molecular surface point to be defined. A two-dimensional (2D) map, the iso-depth contour map, and a three-dimensional (3D) representation, the iso-depth lines, allow the topography of a molecular surface to be displayed in terms of knobs (high depth) and holes (low depth).
Radiotherapy and Oncology, 1995
R ADIOTHERAPY a ONCOLOGY Early breast cancer: influence of type of boost (electrons vs iridium-19... more R ADIOTHERAPY a ONCOLOGY Early breast cancer: influence of type of boost (electrons vs iridium-192 implant) on local control and cosmesis after conservative surgery and radiation therapy *
Radiotherapy and Oncology, 1997
To evaluate possibility of breast-conserving therapy and outcome for patients with locally advanc... more To evaluate possibility of breast-conserving therapy and outcome for patients with locally advanced non-inflammatory breast cancer (LABC) and stage II >3 cm in diameter after primary chemotherapy (CT) followed by external preoperative irradiation (RT). Between 1982 and 1990, 147 patients were treated by four courses of induction CT (doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil) followed by preoperative RT (45 Gy to the breast and nodal areas) and a fifth course of CT. Three different loco-regional approaches were proposed depending on tumour characteristics and tumour response. After completion of local therapy, all patients received a sixth course of CT and a maintenance adjuvant CT regimen without anthracycline. Mastectomy and axillary dissection were performed in 52 patients, and conservative treatment in 95 patients (48 achieved complete remission and received additional radiation boost to initial tumour bed; 47 had a residual mass < or =3 cm in diameter and were treated by wide excision and axillary dissection followed by a boost to the excision site. Ten-year actuarial loco-regional failure rate was 20% after RT alone, 23% after wide excision and RT and 6% after mastectomy (P = 0.85). After multivariate analysis, possibility of breast-conserving therapy was related to initial tumour size. Ten-year overall survival rate was 66%; it was not influenced by local treatment (conservative vs. non-conservative local treatment, P = 0.89). However, local failure significantly decreased overall survival (P < 0.0001). After multivariate analysis, tumour response after induction CT and clinical stage had a significant impact on survival. The present data indicate that induction CT followed by preoperative RT may permit the selection of some patients with LABC or stage II >3 cm for conservative treatment. The impact of this treatment modality on long term survival remains to be established.
Radiotherapy and Oncology, 1995
Journal of Molecular Endocrinology, 2005
To explore the mechanisms whereby estrogen and antiestrogen (tamoxifen (TAM)) can regulate breast... more To explore the mechanisms whereby estrogen and antiestrogen (tamoxifen (TAM)) can regulate breast cancer cell growth, we investigated gene expression changes in MCF7 cells treated with 17β-estradiol (E2) and/or with 4-OH-TAM. The patterns of differential expression were determined by the ValiGen Gene IDentification (VGID) process, a subtractive hybridization approach combined with microarray validation screening. Their possible biologic consequences were evaluated by integrative data analysis. Over 1000 cDNA inserts were isolated and subsequently cloned, sequenced and analyzed against nucleotide and protein databases (NT/NR/EST) with BLAST software. We revealed that E2 induced differential expression of 279 known and 28 unknown sequences, whereas TAM affected the expression of 286 known and 14 unknown sequences. Integrative data analysis singled out a set of 32 differentially expressed genes apparently involved in broad cellular mechanisms. The presence of E2 modulated the expressio...
International Journal of Radiation Oncology*Biology*Physics, 1994
Conclusions: Organ motion can be an important consideration in treatment planning. The method des... more Conclusions: Organ motion can be an important consideration in treatment planning. The method described here requires only slightly more computation time than the currently employed dose calculation for plans without organ motion, and can be readily extended to include the effects of patient setup errors.
International Journal of Radiation Oncology*Biology*Physics, 1998
Purpose: Stereotactic radiotherapy delivered in a high-dose single fraction is an effective techn... more Purpose: Stereotactic radiotherapy delivered in a high-dose single fraction is an effective technique to obliterate intracranial arteriovenous malformations (AVM). To attempt to analyze the relationships between dose, volume, and obliteration rates, we studied a group of patients treated using single-isocenter treatment plans. Methods and Materials: From May 1986 to December 1989, 100 consecutive patients with angiographically proven AVM had stereotactic radiotherapy delivered as a high-dose single fraction using a single-isocenter technique. Distribution according to Spetzler-Martin grade was as follows: 79 grade 1-3, three grade 4, 0 grade 5, and 18 grade 6. The target volume was spheroid in 74 cases, ellipsoid in 11, and large and irregular in 15. The targeted volume of the nidus was estimated using two-dimensional stereotactic angiographic data and, calculated as an ovoid-shaped lesion, was 1900 ؎ 230 mm 3 (median 968 mm 3 ; range 62-11, 250 mm 3). The mean minimum target dose (D min) was 19 ؎ 0.6 Gy (median 20 Gy; range: 3-31.5). The mean volume within the isodose which corresponded to the minimum target dose was 2500 ؎ 300 mm 3 (median 1200 mm 3 ; range 75-14 900 mm 3). The mean maximum dose (D max) was 34.5 ؎ 0.5 Gy (median 35 Gy; range 15-45). The mean angiographic follow-up was 42 ؎ 2.3 months (median 37.5; range 7-117). Results: The absolute obliteration rate was 51%. The 5-year actuarial obliteration rate was 62.5 ؎ 7%. After univariate analysis, AVM obliteration was influenced by previous surgery (p ؍ 0.0007), D min by steps of 5 Gy (p ؍ 0.005), targeted volume of the nidus (<968 mm 3 vs. >968 mm 3 ; p ؍ 0.015), and grade according to Spetzler-Martin (grade 1-3 vs. grade 4-6; p ؍ 0.011). After multivariate analysis, the independent factors influencing AVM obliteration were the D min [relative risk (RR) 1.9; 95% confidence interval (CI) 1.4-2.5; p < 0.0001] and grade distribution according to Spetzler-Martin (RR 1.4; 95% CI 1.1-1.7; p ؍ 0.010). Delayed complications were observed in eight patients. The 5-year actuarial rate of delayed complications was 7.4%. Conclusion: After stereotactic radiotherapy delivered in a single high dose using a single-isocenter technique, the success rate for complete obliteration is independently correlated to D min but does not seem to be influenced by D max and the targeted volume of the nidus.
International Journal of Radiation Oncology*Biology*Physics, 1999
To identify predicting factors for local failure and increased risk of distant metastases by stat... more To identify predicting factors for local failure and increased risk of distant metastases by statistical analysis of the data after breast-conserving treatment for early breast cancer. Between January 1976 and December 1993, 528 patients with nonmetastatic T1 (tumors < or = 1 cm [n = 197], >1 cm [n = 220]) or T2 (tumors < or = 3 cm [n = 111]) carcinoma of the breast underwent wide excision (n = 435) or quadrantectomy (n = 93) with axillary dissection (negative nodal status [n-]: 396; 1-3 involved nodes: 100; >3 involved nodes: 32). Radiotherapy consisted of 45 Gy to the entire breast via tangential fields. Patients with positive axillary lymph nodes received 45 Gy to the axillary and supraclavicular area. Patients with positive axillary nodes and/or inner or central tumor locations received 50 Gy to the internal mammary lymph node area. A boost dose was delivered to the primary site by iridium 192 Implant in 298 patients (mean total dose: 15.2+/-0.07 Gy, range: 15-25 Gy) or by electrons in 225 patients (mean total dose: 14.8+/-0.09 Gy, range: 5-20 Gy). The mean age was 52.5+/-0.5 years (range: 26-86 years) and 267 patient were postmenopausal. Histologic types were as follows: 463 infiltrating ductal carcinomas, 39 infiltrating lobular carcinomas, and 26 other histotypes. Grade distribution according to the Scarff, Bloom, and Richardson (SBR) classification was as follows: 149 grade 1, 271 grade 2, 73 grade 3, and 35 nonclassified. The mean tumor size was 1.6+/-0.3 cm (range: 0.3-3 cm). The intraductal component of the primary tumor was extensive (EIC = IC > or = 25%) in 39 patients. Tumors were microscopically bifocal in 33 cases. Margins were assessed in the majority of cases by inking of the resection margins and were classified as positive in 13 cases, close (< or = 2 mm) in 21, negative (>2 mm tumor-free margin) in 417, and indeterminate in 77. Peritumoral vascular invasion was observed in 40 patients. Tamoxifen was administered for at least 2 years in 176 patients. At least six cycles of adjuvant systemic chemotherapy were administered in 116 patients. The mean follow-up period from the beginning of the treatment was 84.5+/-1.7 months. First events included 44 isolated local recurrences, 8 isolated axillary node recurrences, 44 isolated distant metastases, 1 local recurrence with synchronous axillary node recurrence, 7 local recurrences with synchronous metastases, and 2 local recurrences with synchronous axillary node recurrences and distant metastases. Of 39 pathologically evaluable local recurrences, 33 were classified as true local recurrences and 6 as ipsilateral new primary carcinomas. Seventy patients died (47 of breast carcinoma, 4 of other neoplastic diseases, 10 of other diseases and 9 of unknown causes). The 5- and 10-year rates were, respectively: specific survival 93% and 86%, disease-free survival 85% and 75%, distant metastasis 8.5% and 14%, and local recurrence 7% and 14%. Mean intervals from the beginning of treatment for local recurrence or distant metastases were, respectively, 60+/-6 months (median: 47 months, range: 6-217 months) and 49.5+/-5.4 months (median: 33 months, range: 6-217 months). After local recurrence, salvage mastectomy was performed in 46 patients (85%) and systemic hormonal therapy and/or chemotherapy was administered to 43 patients. The 5-year specific survival rate after treatment for local recurrence was 78+/-8.2%. Multivariate analysis (multivariate generalization of the proportional hazards model) showed that the probability of local control was decreased by the following four independent factors: young age (< or = 40 yr vs. >40 yr; relative risk [RR]: 3.15, 95% confidence interval [CI]: 1.7-5.8, p = 0.0002), premenopausal status (pre vs. post; RR: 2.9, 95% CI: 1.4-6, p = 0.0048), bifocality (uni- vs. bifocal; RR: 2.7, 95% CI: 2.6-2.8,p = 0.018), and extensive intraductal component (IC <25% vs. IC > or = 25%; RR: 2.6, 95% CI: 13-5.2, p = 0
International Journal of Radiation Oncology*Biology*Physics, 2001
To identify prognostic factors and treatment toxicity in a series of operable endometrial adenoca... more To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. Between November 1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged according to the 1988 FIGO staging system (225 Stage IB, 107 Stage IC, 4 Stage IIA, 35 Stage IIB, 30 Stage IIIA, 6 Stage IIIB, and 30 Stage IIIC), underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph node dissection. The chronology of adjuvant RT was not randomized and depended on the usual practices of the surgical teams. Seventy-nine pts (Group I) received preoperative low-dose-rate uterovaginal brachytherapy (mean dose [MD]: 57 Gy). Three hundred fifty-eight pts (Group II) received postoperative RT. One hundred ninety-six pts received low-dose-rate vaginal brachytherapy alone (MD: 50 Gy). One hundred fifty-eight pts had external beam pelvic RT (MD: 46 Gy) followed by low-dose-rate vaginal brachytherapy (MD: 17 Gy). Four pts had external beam pelvic RT alone (MD: 47 Gy). The mean follow-up from the beginning of treatment was 128 months. The 10-year disease-free survival rate was 86%. From 57 recurrences, only 12 were isolated locoregional recurrences. The independent factors decreasing the probability of disease-free survival were as follows: histologic type (clear-cell carcinoma, p = 0.038), largest histologic tumor diameter >3 cm (p = 0.015), histologic grade (p = 0.008), myometrial invasion > 1/2 (p = 0.005), and 1988 FIGO staging system (p = 9.10(-8)). In Group II, the addition of external beam pelvic RT did not seem to independently improve vaginal or pelvic control. The postoperative complication rate was 7%. The independent factors increasing the risk of postoperative complications were stage FIGO (p = 0.02) and pelvic lymph node dissection (p = 0.011). The 10-year rate for Grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 3.1%. External beam pelvic RT independently increased the rate for Grade 3 and 4 late complication (RR: 5.6, p = 0.0096). Postoperative external beam pelvic RT increases the risk of late radiation complications. After surgical and histopathologic staging with pelvic lymph node dissection, in subgroup of "intermediate-risk" patients (Stage IA Grade 3, IB-C and II), postoperative vaginal brachytherapy alone is probably sufficient to obtain a good therapeutic index. Results for patients with Stage III tumor are not satisfactory.
International Journal of Radiation Oncology*Biology*Physics, 1995
Purpose-Chemotherapy plays an increasingly important role in the treatment of both node negative ... more Purpose-Chemotherapy plays an increasingly important role in the treatment of both node negative and node positive breast cancer patients, but the optimal sequencing of chemotherapy and radiation therapy is not well established Our goal is to evaluate the interaction of sequence and type of chemotherapy and hormonal therapy given with radiation therapy on the cosmetic outcome and the incidence of complications of stage I and II breast cancer patients treated with breast conserving therapy
Hepatology 26(4 Part, Apr 26, 1997
Afin d'evaluer les possibilites de traitement conservateur mammaire et l'evolution de pat... more Afin d'evaluer les possibilites de traitement conservateur mammaire et l'evolution de patientes atteintes d'un cancer du sein localement avance (CSLA) non inflammatoire et stade II de plus de 3 cm de diametre apres une chimiotherapie premiere (CT) suivie d'une irradiation externe pre-operatoire (RT), nous avons revu 147 patientes traitees de 1982 a 1990, avec une mediane de recul depuis le debut de traitement de 94 mois. Le traitement d'induction comprenait 4 cycles de CT (doxorubicine, vincristine, 5-fluorouracile, cyclophosphamide), suivis d'une radiotherapie pre-operatoire (45 Gy en 4,5 semaines dans le sein et les aires ganglionnaires homolaterales) et d'un cinquieme cycle de CT. Trois approches therapeutiques loco-regionales etaient proposees en fonction de la reponse tumorale. Pour 52 patientes (35 %) avec une tumeur residuelle de plus de 3 cm de diametre, ou retro-areolaire, ou plurifocale, une mastectomie avec curage axillaire a ete realisee. Quat...
Journal of Experimental Medicine, 2014
Trail+DX5−Eomes− natural killer (NK) cells arise in the mouse fetal liver and persist in the adul... more Trail+DX5−Eomes− natural killer (NK) cells arise in the mouse fetal liver and persist in the adult liver. Their relationships with Trail−DX5+ NK cells remain controversial. We generated a novel Eomes-GFP reporter murine model to address this question. We found that Eomes− NK cells are not precursors of classical Eomes+ NK cells but rather constitute a distinct lineage of innate lymphoid cells. Eomes− NK cells are strictly dependent on both T-bet and IL-15, similarly to NKT cells. We observed that, in the liver, expression of T-bet in progenitors represses Eomes expression and the development of Eomes+ NK cells. Reciprocally, the bone marrow (BM) microenvironment restricts T-bet expression in developing NK cells. Ectopic expression of T-bet forces the development of Eomes− NK cells, demonstrating that repression of T-bet is essential for the development of Eomes+ NK cells. Gene profile analyses show that Eomes− NK cells share part of their transcriptional program with NKT cells, incl...
The Journal of experimental medicine, Jan 26, 2015
Natural killer (NK) cell maturation is a tightly controlled process that endows NK cells with fun... more Natural killer (NK) cell maturation is a tightly controlled process that endows NK cells with functional competence and the capacity to recognize target cells. Here, we found that the transcription factor (TF) Zeb2 was the most highly induced TF during NK cell maturation. Zeb2 is known to control epithelial to mesenchymal transition, but its role in immune cells is mostly undefined. Targeted deletion of Zeb2 resulted in impaired NK cell maturation, survival, and exit from the bone marrow. NK cell function was preserved, but mice lacking Zeb2 in NK cells were more susceptible to B16 melanoma lung metastases. Reciprocally, ectopic expression of Zeb2 resulted in a higher frequency of mature NK cells in all organs. Moreover, the immature phenotype of Zeb2(-/-) NK cells closely resembled that of Tbx21(-/-) NK cells. This was caused by both a dependence of Zeb2 expression on T-bet and a probable cooperation of these factors in gene regulation. Transgenic expression of Zeb2 in Tbx21(-/-) N...
Cancer/Radiothérapie, 1998
Cancer radiothérapie : journal de la Société française de radiothérapie oncologique, 2001
To identify prognostic factors and treatment toxicity in a series of operable endometrial adenoca... more To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. Between November 1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged according to the 1988 FIGO staging system, underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph node dissection. The chronology of RT was not randomized and depended on the usual practices of the surgical teams. Group I: 79 pts received preoperative uterovaginal brachytherapy (mean total dose [MD]: 57 Gy). Group II: 358 pts received postoperative RT (196 pts received vaginal brachytherapy alone [MD: 50 Gy], 158 pts had external beam pelvis RT [EPRT] [MD: 46 Gy over 5 weeks] followed by vaginal brachytherapy [MD: 17 Gy], and 4 pts had EPRT alone [MD: 46 Gy over 5 weeks]). The mean follow-up was 128 months. The 10-year disease-free survival rate was 86%. From 57 recurrences, 12 were isolated locoregionally. Multivaria...
Cancer radiothérapie : journal de la Société française de radiothérapie oncologique
Retrospective study to analyze the results of external beam radiation treatment with or without s... more Retrospective study to analyze the results of external beam radiation treatment with or without surgery for loco-regional recurrence of adenocarcinoma of the rectum following previous surgery without pre- or post-operative radiotherapy. Between March 1973 and November 1991, 211 patients with loco-regional recurrence of rectum cancer were treated with external beam radiation treatment. Radical surgery was the only initial treatment modality. Surgical resection of local recurrence was done in 36 patients and only 17 patients could undergo complete resection. Forty-seven patients underwent radiotherapy (RT) combined with surgery and 164 received external beam radiation treatment alone to a mean total dose of 46 Gy. Among the 151 patients whose recurrence was revealed by pain, 64 (42%) were considered to have a complete symptomatic response after loco-regional treatment with radiosurgery or RT alone. The mean duration of response was 12 months. The 3-year overall survival rate was 16%. ...
Bulletin du cancer. Radiothérapie : journal de la Société française du cancer : organe de la société française de radiothérapie oncologique, 1995
From 1977 to 1988, 120 consecutive patients with a diagnosis of low-grade astrocytoma were referr... more From 1977 to 1988, 120 consecutive patients with a diagnosis of low-grade astrocytoma were referred to our department for radiotherapy. Fourty-one patients (group 1) underwent surgery and post operative external radiation therapy (2 gross total resections and 39 subtotal resections). Sixty-nine patients underwent exclusive external radiotherapy (group 2). In ten patients, the irradiation was delivered by stereotactic implantation of iridium-192 wires into the tumor with or without external irradiation (group 3). Ten had pilocytic astrocytomas (mean age, 24 years) and twenty had microcystic astrocytomas (mean age, 35.4 years). The 5- and 10-year survival rates were 55.6% and 44.4%, respectively and 55% and 48%. Ninety astrocytomas were classified as "ordinary" astrocytoma (mean age, 36.8 years). The 5- and 10-year overall survival rates were 51% and 20.5%, respectively. The same probabilities at 5 and 10 years were 65% and 37% respectively, for group 1, 38.8% and 12.7% for ...
Journal of molecular graphics, 1994
The representation and display of protein surfaces are useful in many areas of molecular modeling... more The representation and display of protein surfaces are useful in many areas of molecular modeling, and surface shape study is particularly important in the analysis of protein-ligand interactions. We introduce here the notion of the molecular surface convex hull, allowing the depth of any molecular surface point to be defined. A two-dimensional (2D) map, the iso-depth contour map, and a three-dimensional (3D) representation, the iso-depth lines, allow the topography of a molecular surface to be displayed in terms of knobs (high depth) and holes (low depth).
Radiotherapy and Oncology, 1995
R ADIOTHERAPY a ONCOLOGY Early breast cancer: influence of type of boost (electrons vs iridium-19... more R ADIOTHERAPY a ONCOLOGY Early breast cancer: influence of type of boost (electrons vs iridium-192 implant) on local control and cosmesis after conservative surgery and radiation therapy *
Radiotherapy and Oncology, 1997
To evaluate possibility of breast-conserving therapy and outcome for patients with locally advanc... more To evaluate possibility of breast-conserving therapy and outcome for patients with locally advanced non-inflammatory breast cancer (LABC) and stage II >3 cm in diameter after primary chemotherapy (CT) followed by external preoperative irradiation (RT). Between 1982 and 1990, 147 patients were treated by four courses of induction CT (doxorubicin, vincristine, cyclophosphamide, 5-fluorouracil) followed by preoperative RT (45 Gy to the breast and nodal areas) and a fifth course of CT. Three different loco-regional approaches were proposed depending on tumour characteristics and tumour response. After completion of local therapy, all patients received a sixth course of CT and a maintenance adjuvant CT regimen without anthracycline. Mastectomy and axillary dissection were performed in 52 patients, and conservative treatment in 95 patients (48 achieved complete remission and received additional radiation boost to initial tumour bed; 47 had a residual mass < or =3 cm in diameter and were treated by wide excision and axillary dissection followed by a boost to the excision site. Ten-year actuarial loco-regional failure rate was 20% after RT alone, 23% after wide excision and RT and 6% after mastectomy (P = 0.85). After multivariate analysis, possibility of breast-conserving therapy was related to initial tumour size. Ten-year overall survival rate was 66%; it was not influenced by local treatment (conservative vs. non-conservative local treatment, P = 0.89). However, local failure significantly decreased overall survival (P < 0.0001). After multivariate analysis, tumour response after induction CT and clinical stage had a significant impact on survival. The present data indicate that induction CT followed by preoperative RT may permit the selection of some patients with LABC or stage II >3 cm for conservative treatment. The impact of this treatment modality on long term survival remains to be established.
Radiotherapy and Oncology, 1995
Journal of Molecular Endocrinology, 2005
To explore the mechanisms whereby estrogen and antiestrogen (tamoxifen (TAM)) can regulate breast... more To explore the mechanisms whereby estrogen and antiestrogen (tamoxifen (TAM)) can regulate breast cancer cell growth, we investigated gene expression changes in MCF7 cells treated with 17β-estradiol (E2) and/or with 4-OH-TAM. The patterns of differential expression were determined by the ValiGen Gene IDentification (VGID) process, a subtractive hybridization approach combined with microarray validation screening. Their possible biologic consequences were evaluated by integrative data analysis. Over 1000 cDNA inserts were isolated and subsequently cloned, sequenced and analyzed against nucleotide and protein databases (NT/NR/EST) with BLAST software. We revealed that E2 induced differential expression of 279 known and 28 unknown sequences, whereas TAM affected the expression of 286 known and 14 unknown sequences. Integrative data analysis singled out a set of 32 differentially expressed genes apparently involved in broad cellular mechanisms. The presence of E2 modulated the expressio...
International Journal of Radiation Oncology*Biology*Physics, 1994
Conclusions: Organ motion can be an important consideration in treatment planning. The method des... more Conclusions: Organ motion can be an important consideration in treatment planning. The method described here requires only slightly more computation time than the currently employed dose calculation for plans without organ motion, and can be readily extended to include the effects of patient setup errors.
International Journal of Radiation Oncology*Biology*Physics, 1998
Purpose: Stereotactic radiotherapy delivered in a high-dose single fraction is an effective techn... more Purpose: Stereotactic radiotherapy delivered in a high-dose single fraction is an effective technique to obliterate intracranial arteriovenous malformations (AVM). To attempt to analyze the relationships between dose, volume, and obliteration rates, we studied a group of patients treated using single-isocenter treatment plans. Methods and Materials: From May 1986 to December 1989, 100 consecutive patients with angiographically proven AVM had stereotactic radiotherapy delivered as a high-dose single fraction using a single-isocenter technique. Distribution according to Spetzler-Martin grade was as follows: 79 grade 1-3, three grade 4, 0 grade 5, and 18 grade 6. The target volume was spheroid in 74 cases, ellipsoid in 11, and large and irregular in 15. The targeted volume of the nidus was estimated using two-dimensional stereotactic angiographic data and, calculated as an ovoid-shaped lesion, was 1900 ؎ 230 mm 3 (median 968 mm 3 ; range 62-11, 250 mm 3). The mean minimum target dose (D min) was 19 ؎ 0.6 Gy (median 20 Gy; range: 3-31.5). The mean volume within the isodose which corresponded to the minimum target dose was 2500 ؎ 300 mm 3 (median 1200 mm 3 ; range 75-14 900 mm 3). The mean maximum dose (D max) was 34.5 ؎ 0.5 Gy (median 35 Gy; range 15-45). The mean angiographic follow-up was 42 ؎ 2.3 months (median 37.5; range 7-117). Results: The absolute obliteration rate was 51%. The 5-year actuarial obliteration rate was 62.5 ؎ 7%. After univariate analysis, AVM obliteration was influenced by previous surgery (p ؍ 0.0007), D min by steps of 5 Gy (p ؍ 0.005), targeted volume of the nidus (<968 mm 3 vs. >968 mm 3 ; p ؍ 0.015), and grade according to Spetzler-Martin (grade 1-3 vs. grade 4-6; p ؍ 0.011). After multivariate analysis, the independent factors influencing AVM obliteration were the D min [relative risk (RR) 1.9; 95% confidence interval (CI) 1.4-2.5; p < 0.0001] and grade distribution according to Spetzler-Martin (RR 1.4; 95% CI 1.1-1.7; p ؍ 0.010). Delayed complications were observed in eight patients. The 5-year actuarial rate of delayed complications was 7.4%. Conclusion: After stereotactic radiotherapy delivered in a single high dose using a single-isocenter technique, the success rate for complete obliteration is independently correlated to D min but does not seem to be influenced by D max and the targeted volume of the nidus.
International Journal of Radiation Oncology*Biology*Physics, 1999
To identify predicting factors for local failure and increased risk of distant metastases by stat... more To identify predicting factors for local failure and increased risk of distant metastases by statistical analysis of the data after breast-conserving treatment for early breast cancer. Between January 1976 and December 1993, 528 patients with nonmetastatic T1 (tumors < or = 1 cm [n = 197], >1 cm [n = 220]) or T2 (tumors < or = 3 cm [n = 111]) carcinoma of the breast underwent wide excision (n = 435) or quadrantectomy (n = 93) with axillary dissection (negative nodal status [n-]: 396; 1-3 involved nodes: 100; >3 involved nodes: 32). Radiotherapy consisted of 45 Gy to the entire breast via tangential fields. Patients with positive axillary lymph nodes received 45 Gy to the axillary and supraclavicular area. Patients with positive axillary nodes and/or inner or central tumor locations received 50 Gy to the internal mammary lymph node area. A boost dose was delivered to the primary site by iridium 192 Implant in 298 patients (mean total dose: 15.2+/-0.07 Gy, range: 15-25 Gy) or by electrons in 225 patients (mean total dose: 14.8+/-0.09 Gy, range: 5-20 Gy). The mean age was 52.5+/-0.5 years (range: 26-86 years) and 267 patient were postmenopausal. Histologic types were as follows: 463 infiltrating ductal carcinomas, 39 infiltrating lobular carcinomas, and 26 other histotypes. Grade distribution according to the Scarff, Bloom, and Richardson (SBR) classification was as follows: 149 grade 1, 271 grade 2, 73 grade 3, and 35 nonclassified. The mean tumor size was 1.6+/-0.3 cm (range: 0.3-3 cm). The intraductal component of the primary tumor was extensive (EIC = IC > or = 25%) in 39 patients. Tumors were microscopically bifocal in 33 cases. Margins were assessed in the majority of cases by inking of the resection margins and were classified as positive in 13 cases, close (< or = 2 mm) in 21, negative (>2 mm tumor-free margin) in 417, and indeterminate in 77. Peritumoral vascular invasion was observed in 40 patients. Tamoxifen was administered for at least 2 years in 176 patients. At least six cycles of adjuvant systemic chemotherapy were administered in 116 patients. The mean follow-up period from the beginning of the treatment was 84.5+/-1.7 months. First events included 44 isolated local recurrences, 8 isolated axillary node recurrences, 44 isolated distant metastases, 1 local recurrence with synchronous axillary node recurrence, 7 local recurrences with synchronous metastases, and 2 local recurrences with synchronous axillary node recurrences and distant metastases. Of 39 pathologically evaluable local recurrences, 33 were classified as true local recurrences and 6 as ipsilateral new primary carcinomas. Seventy patients died (47 of breast carcinoma, 4 of other neoplastic diseases, 10 of other diseases and 9 of unknown causes). The 5- and 10-year rates were, respectively: specific survival 93% and 86%, disease-free survival 85% and 75%, distant metastasis 8.5% and 14%, and local recurrence 7% and 14%. Mean intervals from the beginning of treatment for local recurrence or distant metastases were, respectively, 60+/-6 months (median: 47 months, range: 6-217 months) and 49.5+/-5.4 months (median: 33 months, range: 6-217 months). After local recurrence, salvage mastectomy was performed in 46 patients (85%) and systemic hormonal therapy and/or chemotherapy was administered to 43 patients. The 5-year specific survival rate after treatment for local recurrence was 78+/-8.2%. Multivariate analysis (multivariate generalization of the proportional hazards model) showed that the probability of local control was decreased by the following four independent factors: young age (< or = 40 yr vs. >40 yr; relative risk [RR]: 3.15, 95% confidence interval [CI]: 1.7-5.8, p = 0.0002), premenopausal status (pre vs. post; RR: 2.9, 95% CI: 1.4-6, p = 0.0048), bifocality (uni- vs. bifocal; RR: 2.7, 95% CI: 2.6-2.8,p = 0.018), and extensive intraductal component (IC <25% vs. IC > or = 25%; RR: 2.6, 95% CI: 13-5.2, p = 0
International Journal of Radiation Oncology*Biology*Physics, 2001
To identify prognostic factors and treatment toxicity in a series of operable endometrial adenoca... more To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. Between November 1971 and October 1992, 437 patients (pts) with endometrial carcinoma, staged according to the 1988 FIGO staging system (225 Stage IB, 107 Stage IC, 4 Stage IIA, 35 Stage IIB, 30 Stage IIIA, 6 Stage IIIB, and 30 Stage IIIC), underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy without (n = 140) or with (n = 297) pelvic lymph node dissection. The chronology of adjuvant RT was not randomized and depended on the usual practices of the surgical teams. Seventy-nine pts (Group I) received preoperative low-dose-rate uterovaginal brachytherapy (mean dose [MD]: 57 Gy). Three hundred fifty-eight pts (Group II) received postoperative RT. One hundred ninety-six pts received low-dose-rate vaginal brachytherapy alone (MD: 50 Gy). One hundred fifty-eight pts had external beam pelvic RT (MD: 46 Gy) followed by low-dose-rate vaginal brachytherapy (MD: 17 Gy). Four pts had external beam pelvic RT alone (MD: 47 Gy). The mean follow-up from the beginning of treatment was 128 months. The 10-year disease-free survival rate was 86%. From 57 recurrences, only 12 were isolated locoregional recurrences. The independent factors decreasing the probability of disease-free survival were as follows: histologic type (clear-cell carcinoma, p = 0.038), largest histologic tumor diameter >3 cm (p = 0.015), histologic grade (p = 0.008), myometrial invasion > 1/2 (p = 0.005), and 1988 FIGO staging system (p = 9.10(-8)). In Group II, the addition of external beam pelvic RT did not seem to independently improve vaginal or pelvic control. The postoperative complication rate was 7%. The independent factors increasing the risk of postoperative complications were stage FIGO (p = 0.02) and pelvic lymph node dissection (p = 0.011). The 10-year rate for Grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 3.1%. External beam pelvic RT independently increased the rate for Grade 3 and 4 late complication (RR: 5.6, p = 0.0096). Postoperative external beam pelvic RT increases the risk of late radiation complications. After surgical and histopathologic staging with pelvic lymph node dissection, in subgroup of "intermediate-risk" patients (Stage IA Grade 3, IB-C and II), postoperative vaginal brachytherapy alone is probably sufficient to obtain a good therapeutic index. Results for patients with Stage III tumor are not satisfactory.
International Journal of Radiation Oncology*Biology*Physics, 1995
Purpose-Chemotherapy plays an increasingly important role in the treatment of both node negative ... more Purpose-Chemotherapy plays an increasingly important role in the treatment of both node negative and node positive breast cancer patients, but the optimal sequencing of chemotherapy and radiation therapy is not well established Our goal is to evaluate the interaction of sequence and type of chemotherapy and hormonal therapy given with radiation therapy on the cosmetic outcome and the incidence of complications of stage I and II breast cancer patients treated with breast conserving therapy