[Epidermoid carcinomas of anal canal treated with radiation therapy and concomitant chemotherapy (5-fluorouracil and cisplatin)]. / Carcinomes épidermoïdes du canal anal traités par association concomitante de radiothérapie et de chimiothérapie. Evaluation des résultats fonctionnels.

PURPOSE: To evaluate our results after radiation therapy and concomitant chemotherapy in terms of local control, survival and toxicity in patients with anal cancer. METHODS AND PATIENTS: Between November 1990 and January 2002, 60 patients (pts) were treated with radiation therapy and concomitant chemotherapy. The T-stage according to the 2001 UICC classification were: 2 T1, 26 T2, 25 T3, and 7 T4. There were 20 pts with nodal involvement at presentation. The treatment started with external beam RT (median dose: 45 Gy) and concomitant chemotherapy using 5-fluorouracil and cisplatin during the first week and the fifth week of external beam RT (EBRT). After a rest period of 4 to 6 weeks, a boost of 20 Gy was delivered by EBRT in 58 pts and by interstitial (192)Ir brachytherapy in 2 pts. Mean follow-up were 78.5 months. RESULTS: At the end of RT with concomitant chemotherapy local tumor clinical complete response rate was 83%. Out of 10 non responders or local progression, 5 (50%) were salvaged with abdominoperineal resection (APR). Out of 5 local tumor relapses, 3 were salvaged with APR. The overall local tumor control (LC) rate with or without salvage local treatment were 88%. LC rate with a good anal function scoring (score 0 and 1) was 70%. Among 43 pts who preserved their anus, 98% had a good anal function scoring. The 5-year disease-free survival was 75%. After multivariate analysis, 2 independent predicting factors significantly influenced the disease-free survival: HIV-positive pts (negative vs positive, P=0.032) and clinical tumor response after the first course of radiotherapy (<50% vs >or=50%, P=0.00032). Acute grade 2 or 3 toxicities were low: haematological toxicity in 4 pts and intestinal complication corresponding to diarrhea in 10 pts. Late severe complication was observed in 3 pts: 2 pts with painful necrosis of the anus requiring colostomy and 1 pt with grade 3 rectal bleeding. CONCLUSION: We confirm the good results with RT and concomitant chemotherapy. The clinical tumor response after the first course of RT and concomitant chemotherapy is probably the most important predictive factor on the disease-free survival. For patients with T3 or T4 lesion and tumor regression

[Combined flow cytometry determination of S-phase fraction and DNA ploidy is an independent prognostic factor in node-negative invasive breast carcinoma: review of a series of 271 patients with stage I and II breast cancer]. / L'évaluation conjointe du contenu en ADN et de la fraction de cellules en phase S est un paramètre pronostique indépendant dans les cancers du sein de stades I et II.

PURPOSE: To assess the significance of S-phase fraction (SPF) and DNA ploidy evaluated by DNA flow cytometry as prognostic markers in stage I or II breast cancer. PATIENTS AND METHODS: A series of 271 patients, treated by surgery, radiotherapy+/-systemic therapy was analysed (median follow up: 64 months). Standardized flow cytometry cell preparation from frozen samples and consensus rules for data interpretation were followed. Three SPF classes were defined on the basis of tertiles after adjustment for ploidy. Four groups were defined based on combinations of DNA ploidy (DIP: diploid; ANEUP: aneuploid) and SPF: DIP and low SPF (DL, N=37), DIP and medium or high SPF (DMH, N=76), ANEUP and low SPF (AL, N=24), ANEUP and medium or high SPF (AMH, N=68). Local control rate (LCR), disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS) were correlated with DNA ploidy, SPF, DL to AMH groups, T and N stages, SBR grading, age, and hormonal status on univariate and multivariate analysis (Cox model). RESULTS: On univariate analysis, DFS and LCR were higher for DIP tumours. High SPF values were associated with shorter DFS. LCR, MFS, DFS, and OS rates were significantly different with an increasingly poorer prognosis from DL to AMH. On multivariate analysis, groups DL to AMH, histological node involvement and T stage were independently associated with MFS, and DFS. In N- patients, DL to AMH remained independent for MFS and DFS. For SBR III tumours, MFS and OS were significantly different in DL to AMH groups. These results strongly support the use of combined evaluation of DNA ploidy and SPF as independent parameters in clinical trials for N- stage I and II breast cancer.

[Impact of computed tomography (CT) and 18F-deoxyglucose-coincidence detection emission tomography (FDG-CDET) image fusion for optimisation of conformal radiotherapy in non-small-cell lung cancers]. / Tomographie par émission de positons et détection en coïncidence (TEDC) et recalage d'images de simulation virtuelle par tomodensitométrie. Impact sur la planification de la radiothérapie conformationnelle des cancers bronchiques non à petites cellules.

UNLABELLED: To report a retrospective study concerning the impact of fused 18F-fluorodeoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography (CT) images on three-dimensional conformal radiation therapy (3D-CRT) planning for patients with non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: One hundred and one patients consecutively treated for stages I-III NSCLC were studied. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same radiation treatment position. Images were coregistered using five fiducial markers. Target volume delineation was initially performed on the CT images and the corresponding FDG-PET data were subsequently used as an overlay to the CT data to define target volume. RESULTS: FDG-PET identified previously undetected distant metastatic disease in 8 patients making them ineligible for curative CRT (one patient presented some positive uptakes corresponding to concomitant pulmonary tuberculosis). Another patient was ineligible for curative treatment because fused CT/PET images demonstrated excessively extensive intrathoracic disease. The gross tumor volume (GTV) was decreased by CT/PET image fusion in 21 patients (23%) and was increased in 24 patients (26%). The GTV reduction was > or = 25% in 7 patients because CT/PET image fusion reduced pulmonary GTV in 6 patients (3 patients with atelectasis) and mediastinal nodal GTV in 1 patient. The GTV increase was > or = 25% in 14 patients due to an increase of the pulmonary GTV in 11 patients (4 patients with atelectasis) and detection of occult mediastinal lymph node involvement in 3 patients. Among 81 patients receiving a total dose > or = 60 Gy at ICRU point, after CT/PET image fusion, the percentage of total lung volume receiving more than 20 Gy (VL20) increased in 15 cases and decreased in 22 cases. The percentage of total heart volume receiving more than 36 Gy increased in 8 patients and decreased in 14 patients. The spinal cord volume receiving at least 45 Gy (2 patients) decreased. After multivariate analysis, one single independent factor made significant effect of FDG/PET on the modification of the size of the GTV: tumor with atelectasis (P = 0.0001). Conclusion. - Our study confirms that integrated hybrid PET/CT in the treatment position and coregistered images have an impact on treatment planning and management of patients with NSCLC. FDG images using dedicated PET scanners with modern image fusion techniques and respiration-gated acquisition protocols could improve CT/PET image coregistration. However, prospective studies with histological correlation are necessary and the impact on treatment outcome remains to be demonstrated.

[Impact of computed tomography (CT) and 18F-deoxyglucose positron emission tomography (FDG-PET) image fusion for conformal radiotherapy in esophageal carcinoma]. / Tomographie par émission de positons et fusion d'images de simulation virtuelle par tomodensitométrie. Impact sur la planification de la radiothérapie conformationnelle des cancers de l'oesophage.

PURPOSE: To study the impact of fused (18)F-fluoro-deoxy-D-glucose (FDG)-hybrid positron emission tomography (PET) and computed tomography (CT) images on conformal radiation therapy (CRT) planning for patients with esophageal carcinoma. PATIENTS AND METHODS: Thirty-four patients with esophageal carcinoma were referred for concomitant radiotherapy and chemotherapy with radical intent. Each patient underwent CT and FDG-hybrid PET for simulation treatment in the same radiation treatment position. PET-images were coregistered using five fiducial markers. Target delineation was initially performed on CT images and the corresponding PET data were subsequently used as an overlay to CT data to define the target volume. RESULTS: FDG-PET identified previously undetected distant metastatic disease in 2 patients, making them ineligible for curative CRT. The Gross Tumor Volume (GTV) was decreased by CT and FDG image fusion in 12 patients (35%) and was increased in 7 patients (20.5%). The GTV reduction was >or=25% in 4 patients due to reduction of the length of the esophageal tumor. The GTV increase was >or=25% with FDG-PET in 2 patients due to the detection of occult mediastinal lymph node involvement in one patient and an increased length of the esophageal tumor in the other patient. Modifications of the GTV affected the planning treatment volume (PTV) in 18 patients. Modifications of delineation of GTV and displacement of the isocenter of PTV by FDG-PET also affected the percentage of total lung volume receiving more than 20 Gy (VL20) in 25 patients (74%), with a dose reduction in 12 patients and a dose increase in 13 patients. CONCLUSION: In our study, CT and FDG-PET image fusion appeared to have an impact on treatment planning and management of patients with esophageal carcinoma related to modifications of GTV. The impact on treatment outcome remains to be demonstrated.

Combined flow cytometry determination of S-phase fraction and DNA ploidy is an independent prognostic factor in node-negative invasive breast carcinoma: analysis of a series of 271 patients with stage I and II breast cancer.

PURPOSE: To assess the significance of S-phase fraction (SPF) and DNA ploidy evaluated by DNA flow cytometry as prognostic markers in stage I or II breast cancer. PATIENTS AND METHODS: A series of 271 patients, treated by surgery, radiotherapy +/- systemic therapy was analyzed (median follow up: 64 months). Standardized flow cytometry cell preparation from frozen samples and consensus rules for data interpretation were followed. Three SPF classes were defined on the basis of tertiles after adjustment for ploidy. Four groups were defined based on combinations of DNA ploidy (DIP: diploid; ANEUP: aneuploid) and SPF: DIP and low SPF (DL, n=37), DIP and medium or high SPF (DMH, n=76), ANEUP and low SPF (AL, n=24), ANEUP and medium or high SPF (AMH, n=68). Local control rate (LCR), disease-free survival (DFS), metastasis-free survival (MFS), and overall survival (OS) were correlated with DNA ploidy, SPF, DL to AMH groups, T and N stages, SBR grading, age, and hormonal status on univariate and multivariate analysis (Cox model). RESULTS: On univariate analysis, DFS and LCR were higher for DIP tumours. High SPF values were associated with shorter DFS. LCR, MFS, DFS, and OS rates were significantly different with an increasingly poorer prognosis from DL to AMH. On multivariate analysis, groups DL to AMH, histological node involvement and T stage were independently associated with MFS, and DFS. In N- patients, DL to AMH remained independent for MFS and DFS. For SBR III tumours, MFS and OS were significantly different in DL to AMH groups. These results strongly support the use of combined evaluation of DNA ploidy and SPF as independent parameters in clinical trials for N- stage I and II breast cancer.

[Isolate local failure after breast-conserving treatment for early breast cancer, about 57 cases].

PURPOSE: - To identify predicting factors of local control and survival after isolate local failure by statistical analysis of the data after breast-conserving treatment for early breast cancer. METHODS AND PATIENTS: - In time of local failure, mean age was 54.7 years old, mean tumor size was 19.3 mm and recurrence was more often infiltrating ductal carcinoma (88%). Local recurrence was unifocal in 44 cases and localised outside of the site of the primary tumorectomy in 35 cases. Local failure treatment was a radical mastectomy or parietectomy (53 patients). Hormonotherapy was delivered in 36 patients and chemotherapy was delivered in 26 patients. Mean follow-up was 62 months. RESULTS: - Fifteen patients developed second local recurrence in a mean time of 36 months. Five years local control rate was 68% after the first local failure. Surgery treatment (non-conservative surgery vs. conservative surgery) was the only factor which influenced local control. Six patients developed homolateral axillary and/or supraclavicular node recurrence. Twelve patients underwent metastasis in a mean time of 36 months after the first local recurrence. Five years metastasis free survival rate was 80%. Peritumoral vascular invasion in time of the first local failure increased metastasis risk and node recurrence. Second local failure did not alter metastasis free survival. CONCLUSION: - Peritumoral vascular invasion in time of the first local failure decreased node and metastasis free survival. Surgery should be radical, but the place of chemotherapy and hormonotherapy was not definite.

[The impact of integrating images of positron emission tomography with computed tomography simulation on radiation therapy planning]. / Tomographie par émission de positons et fusion d'images de simulation virtuelle par tomodensitométrie: impact sur la planification de la radiothérapie.

The coregistration of planning CT and 18F-fluoro-deoxy-2-glucose (FDG) positron emission tomography (PET) with patient in the same treatment position is the principally well-established tool for improving the target coverage defined and the target planning volume to treat the metabolic target volume. Most of the interest in the coresgistred CT/PET images on volume delineation has focused on conformal radiation therapy of non-small cell lung cancer. In spite of technical difficulties related to the target volume displacements, and the sensitivity and the specificity of FDG-PET images < 100%, the target volume delineation is significantly changed by the coregistration of FDG-PET images and planning CT by either reduction of the radiation volume (excluding atelectasis or mediastinal lymph node) or the increasing of mediastinal lymph node involvement. Image fusion technique reduces the interobserver variability in target volume delineation. Furthermore, after induction chemotherapy image fusion leads to improve the patient management by detecting locoregional progression disease or the presence of metastatic disease. Other anatomic tumor sites are going to investigate such as: head-and-neck cancer, gynecologic cancer, oesophageal cancer, anal cancer, Hodgkin's disease, and non-Hodgkin's lymphoma. The impact on treatment outcome remains to be demonstrated.

[Epidermoid carcinomas of the anal canal treated with definitive radiation therapy in a series of 305 patients]. / Carcinomes épidermoïdes du canal anal traités par irradiation à visée curative: à propos de 305 patients.

PURPOSE: To identify prognostic factors and treatment toxicity in a serie of epidermoid cancers of the anal canal without evident metastasis. PATIENTS AND METHODS: Between June 1972 and January 1997, 305 patients (pts) were treated with curative-intent radiation therapy (RT). The T-stages according to the 1987 UICC classification were: 26 T1, 141 T2, 104 T3, and 34 T4. There were 49 pts with nodal involvement at presentation. Pretreatment anal function scoring according to our in-house system was: 22 scored 0, 182 scored 1, 74 scored 2, 7 scored 3, 11 scored 4, and 9 not available pts. The treatment started with external beam RT (EBRT) in 303 pts (median dose: 45 Gy). After a rest period of 4 to 6 weeks, a boost of 20 Gy was delivered by EBRT in 279 pts and by interstitial 192Ir brachytherapy (Bcy) in 17 pts. Seven pts received only one course of EBRT (mean dose: 49.5 Gy) and 2 pts were treated with interstitial 192Ir Bcy alone (55 and 60 Gy, respectively). Concomitant chemotherapy (5-fluoro-uracil and either mitomycin C or cisplatin) was delivered to 19 pts. Mean follow-up was 103 months. RESULTS: At the end of RT local tumor clinical complete response (cCR) rate was 80%. Out of 61 non responders or local progressive tumors 27 (44%) were salvaged with abdominoperineal resection (APR). The rate of local tumor relapse (LR) was 12%. Out of 37 LTR, 20 (54%) were salvaged with APR and one with interstitial 192Ir Bcy. The orevall local tumor control (LC) rate with or without salvage local treatment was 84%. LC rate with a good anal function scoring (score 0 and 1) was 56.5%. Among 181/186 available pts who preserved their anus, 94% had a good anal function scoring. For a subgroup of 15 pts with length tumor <2 cm-N0, the LC rate after the end of RT was 100%, the LC rate with or without local salvage treatment was 100%, and among 13 available pts who preserved their anus, the anal function scoring was good in 12 pts (92%). The 10-years disease-free survival was 74%. After multivariate analysis, 3 independent predicting factors significantly influenced the disease-free survival: gap duration between 2 courses of RT (>38 days vs < or =38 days, P =0.0025), pretreatment anal function scoring (0 vs 1 vs 2 vs 3 vs 4, P =4.4 10(-6)), and cCR after the end of RT (no complete response vs complete response, P =2.5 10(-14)). CONCLUSION: We confirm excellent results with RT in T1 and T2 lesions. However, chemoradiotherapy should be prefered to improve survival free of colostomy with a good anal sphincter function for tumors more than or equal to 2 cm in length and locally advanced tumors.

[Radiotherapy of carcinomas of the anal canal. Tenon Hospital experience]. / Traitement des cancers du canal anal par irradiation. Expérience de l'hôpital Tenon.

Since 1980, curative-intent radiation therapy of epidermoid carcinoma of the anal canal is the standard first line treatment. The combined concomitant chemotherapy and radiation therapy is presently established for locally advanced tumors more than 4 cm in length and/or with nodal involvement. We report the Tenon hospital experience since 1972 concerning the long term results after radiation therapy, the modifications of the radiation technique, and the evolution of treatment strategy.

[Operable stage IB and II cancer of the uterine neck: retrospective comparison between preoperative utero-vaginal curietherapy and initial surgery followed by radiotherapy]. / Cancer du col utérin stades IB et II opérable: comparaison rétrospective entre curiethérapie utérovaginale préopératoire et chirurgie première suivies d'une radiothérapie.

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable stages IB and II cervical carcinomas. PATIENTS AND METHODS: Between May 1972 and January 1994, 414 patients (pts) with cervical carcinoma staged according to the 1995 FIGO staging system underwent radical hysterectomy with (n = 380) or without (n = 34) bilateral pelvic lymph node dissection. Lateral ovarian transposition to preserve ovarian function was performed on 12 pts. The methods of radiation therapy (RT) were not randomised and depended on the usual practices of the surgical teams. Group I: 168 pts received postoperative RT (64 pts received vaginal brachytherapy alone [mean total dose (MD): 50 Gy], 93 pts had external beam pelvis RT (EBPRT) [MD: 45 Gy over 5 weeks] followed by vaginal brachytherapy [MD: 20 Gy], and 11 pts had EBPRT alone [MD: 50 Gy over 6 weeks]. Group II: 246 pts received preoperative utero-vaginal brachytherapy [MD: 65 Gy], and 32 of theses 246 pts also received postoperative EBPRT [MD: 45 Gy over 5 weeks] delivered to the parametric and the pelvic lymph nodes with a midline pelvic shield. The mean follow-up was 106 months. RESULTS: The 10-year disease-free survival (DFS) rate was 80%. From 75 recurrences, 35 were isolated locoregional. Multivariate analysis showed that independent factors decreasing the probability of DFS were: both exo and endocervical tumour site (p = 0.047), lymph-vascular space invasion (p = 0.041), age < or = 51 yr (p = 0.013), 1995 FIGO staging system (stage IB1 vs stage IIA, p = 0.004, stage IB1 vs stage IB2, p = 0.0009, and stage IB1 vs stage IIB with 1/3 proximal parametrical infiltration, p = 0.00002), and histological pelvic involved lymph nodes (p = 0.00009). Methods of adjuvant RT did not influence the probability of DFS (group I vs group II, p = 0.10). The postoperative complication rate was 10.2% in group I and 8.9% in group II (p = 0.7) but the postoperative urethral complication rate necessitating surgical intervention with reimplantation was lower in group I than in group II (0.6% vs 2.3%, respectively, p = 0.03). The 10-year rate for grade 3 and 4 late radiation complications according to the LENT-SOMA scoring system was 10.4%. EPRT significantly increased the 10-year rate for grade 3 and 4 late radiation complications (yes vs no: 22% vs 7%, respectively, p = 0.0002). CONCLUSION: In our series, the methods of adjuvant RT (primary surgery vs preoperative uterovaginal brachytherapy) do not seem to influence the prognosis of the stage IB, IIA, and IIB (with 1/3 proximal parametrical involvement only) cervical carcinomas. The postoperative EPRT applied according to histopathological risk factors after surgical treatment increases the risk of late radiation complications.

[Epidermoid carcinoma of the uterine cervix at operable bulky stages IB and II treated with combined primary radiation therapy and surgery]. / Carcinomes épidermoïdes du col utérin opérables de stades IB et II de gros volume traités par irradiation première et chirurgie.

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable bulky stages I and II cervical carcinomas treated with a therapeutic modality combining primary irradiation and surgery. PATIENTS AND METHODS: Between July 1982 and May 1996, 66 patients with bulky squamous-cell cervical carcinomas (stage IB2, IIA, and IIB with 1/3 proximal parametrial invasion) underwent primary external beam pelvic radiation therapy (37.40 Gy to 40 Gy over 4.5 weeks) and low-dose-rate uterovaginal brachytherapy (20 Gy) followed, 5 to 6 weeks later, by class II modified radical hysterectomy with bilateral pelvic lymphadenectomy. The four last patients received concomitant chemotherapy during the first and the fourth radiation week combining 5-FU and cisplatin. A clinical pelvic lymph node involvement had been observed in 7 patients. The clinical median tumor size was 5 cm in diameter (range: 4.5-8 cm). The median follow-up was 97 months. RESULTS: Pathologic complete tumor response in specimen of hysterectomy were observed in 46 patients. Six patients had pathologic unilateral iliac lymph node involvement. The 5- and 10-year specific survival rates were 79 and 74%, respectively. The 5- and 10-year disease-free survival rates were 76% and 71%, respectively. The 10-year local control rate was 85%. The 10-year probability for pelvic recurrence was significantly influenced by the pathologic tumor response: 26% in the residual group vs 5% in the complete tumor response group, P = 0.024). After multivariate analysis, the independent factors decreasing the probability of disease-free survival were: pathologic pelvic lymph node involvement (P = 0.029), and parametrial invasion (P = 0.031). Five late severe complications requiring surgical intervention were observed: 2 bowel obstructions, 1 ureteral stenosis, 1 vesicovaginal fistula, and 1 radiation induced unilateral femoral necrosis. CONCLUSION: A good local control is obtained after combined primary radiation therapy and surgery for bulky stages I and II cervical carcinomas. In our more recent practice, the treatment combines primary concomitant chemoradiation followed by surgery including pelvic and para-aortic lymphadenectomy.

[Endometrial adenocarcinoma treated with combined radiotherapy and surgery: 437 cases]. / Adénocarcinome de l'endomètre traité par association radiochirurgicale: à propos de 437 cas.

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. PATIENTS AND METHODS: 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. RESULTS: The 10-year disease-free survival rate was 86%. From 57 recurrences, 12 were isolated locoregionally. Multivariate analysis showed that independent factors decreasing the probability of disease-free survival were: 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 = 0.0055), and 1988 FIGO staging system (p = 9.10(-8)). In group II, the addition of EPRT did not seem to improve locoregional control. The postoperative complication rate was 7%. The independent factors increasing the risk of postoperative complications were FIGO stage (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%. EPRT independently increased the 10-year rate for grade 3 and 4 late radiation complications (R.R.: 5.6, p = 0.0096). CONCLUSION: EPRT increases the risk of late radiation complications. After surgical and histopathologic staging with pelvic lymph node dissection, in a 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.

[Breast-conserving surgery and irradiation for early breast cancer: value of surgical clips in the surgical cavity]. / Association radiochirurgicale conservatrice des cancers du sein de petit volume: intérêt des clips chirurgicaux dans le lit de tumorectomie.

PURPOSE: To evaluate, qualitatively and quantitatively, the role of surgical clips in planning the tumor bed electron or brachytherapy boost in patients undergoing breast-conserving surgery and radiotherapy. PATIENTS AND METHODS: In 60 patients with breast cancer stage I or II, the excision cavity boundaries were marked by clips at surgery. Patients received a boost with brachytherapy (n = 51) or electron beam (n = 9) after whole breast irradiation. The boost target volume was first planned using clinical, mammography and operative information and its accuracy evaluated by screening the surgical clips and, if necessary, adjusting the field to encompass all clips and to include the scar. Dosimetry was retrospectively performed for each brachytherapy patient and for each surgical clip. RESULTS: It was necessary to modify the target volume field in 11 cases (18%). The average dose received by the surgical clips was 116.1% of the dose delivered to the reference isodose (median: 101.75%, range: 16-457%). However, dose heterogeneity was important in the same patient and between patients. CONCLUSION: Delineation of the boost target volume with surgical clips is more accurate than with clinical landmarks alone but this technique does not allow measurements of the clip-chest wall and clip-skin distances. Virtual simulation with CT-scan cuts is recommended for optimising boost planning.

[Re-irradiation of cerebral arteriovenous malformations. Experience of the Sainte-Anne-Tenon Group]. / Ré-irradiation de malformations artério-veineuses cérébrales. Expérience du Groupe Sainte-Anne-Tenopn.

BACKGROUND AND PURPOSE: Between 20 to 50% of cerebral arteriovenous malformations treated with radiosurgery (RS) fail to obliterate 2 to 5 years after irradiation. Patients are not protected against the risks leading to treatment. Two therapeutic options can be used to eradicate the persisting nidus: micro-surgery and a second irradiation. Our group has reirradiated 39 such patients. MATERIAL: From 1989 to 2000, 39 patients have been reirradiated (14 females and 25 males; median age 31 years). There were more left lesions: 59% than right (35%) and 5% on midline. The most frequent locations were: temporal 12 cases; parietal 8 cases; frontal 7 cases; thalamus 7 cases. The predominant first symptoms were hemorrhage (68.5%) and seizure (15.8%). Prior RS, 21/39 patients had embolization (53.8%) and 3 surgery. Method. Treatment has been performed with the same system for the first and the second radiosurgery for 37 patients. Planification and dosimetry improved during that period. The level of dose was similar for the 2 RS. MRI has been used as a non invasive follow-up tool. RESULTS: Only 28 patients were evaluable because 7/39 patients had the second radiosurgery in 1999 or in 2000 and data were lacking at the time of writing for 4 patients. Obliteration rate was 17/28 (60.7%). Nine patients bled between the two radiosurgery procedures. COMPLICATIONS: 4 new regressive deficits occurred after the second radiosurgery. The rate of parenchymal changes were higher, after the second radiosurgery. Except one patient who died of a non-related affection 2 years after obliteration of his cerebral arteriovenous malformation, thus 38/39 patients were alive. CONCLUSION: This series was small compared to the potential number of candidates suffering from failure of the first radiosurgery, but the results are promising.

Adenocarcinoma of the endometrium treated with combined irradiation and surgery: study of 437 patients.

PURPOSE: To identify prognostic factors and treatment toxicity in a series of operable endometrial adenocarcinomas. METHODS AND MATERIALS: 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. RESULTS: 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). CONCLUSION: 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.

CT and (18)F-deoxyglucose (FDG) image fusion for optimization of conformal radiotherapy of lung cancers.

PURPOSE: To validate a computed tomography (CT) and (18)F-deoxyglucose (FDG) image fusion procedure and to evaluate its usefulness to facilitate target definition and treatment planning in three-dimensional conformal radiation therapy (3D-CRT) for non-small-cell lung cancer. METHODS AND MATERIALS: Twelve patients were assessed by CT and FDG-coincidence mode dual-head gamma camera (CDET) before radiotherapy. The patients were placed in a similar position during CT and FDG-CDET. Matching was achieved by minimizing the cost function by 3D translation and rotation between four landmarks drawn on the patient's skin. Virtual simulation was performed from image fusion and estimated dose-volume histograms (DVH) were calculated. RESULTS: Quantitative analysis indicated that the matching error was < 5 mm. Fusion of anatomic and metabolic data corrected staging of lymph nodes (N) for 4 patients and staging of metastases for 1 patient. In these 5 patients, DVH revealed that the lung volume irradiated at 20 Gy (Vl(20)) was decreased by an average of 22.8%, and tumor volume irradiated at the 95% isodose (V(95)) was increased by 22% and 8% for 2 patients, respectively, and was decreased by an average of 59% for 3 patients after fusion. No difference in terms of Vl(20) and V(95) was observed for the other 7 patients. CONCLUSION: We have validated CT and FDG-CDET lung image fusion to facilitate determination of lung cancer volumes, which improved the accuracy of 3D-CRT.

[Role of adjuvant therapy in uterine sarcoma: experience of the Curie Institute]. / Intérêt des traitements adjuvants dans les sarcomes utérins: expérience de l'institut Curie.

PURPOSE: Uterine sarcoma is a rare disease and survival is poor. From 1975 to 1995, 73 uterine sarcomas were treated at the Curie Institute, and we analysed prognostics factors of survival. PATIENTS AND METHODS: Seventy-one patients underwent primary surgery, in most cases a radical non conservative surgery and a lymphadenectomy. Every patient had an irradiation (external beam irradiation and/or brachytherapy), and 24 patients received adjuvant chemotherapy. We observed that youngest patients had more leiomyosarcomas and low histologic grade tumours. Median survival was 42 months, and 5-years survival and local control were 36 and 68% respectively. Pelvic recurrences were most often before 2 years. This series demonstrates the impact of adjuvant irradiation on local control. This impact was stronger if the tumour had a high histologic grade (p < 0.01). However, irradiation, as well as chemotherapy, had no impact on the survival. CONCLUSION: The study confirmed that irradiation enable a better local control. However modalities of radiation therapy (brachytherapy and/or external beam radiotherapy, dose, volume), are still controversed.

Hyperfast, early cell response to ionizing radiation.

PURPOSE: To determine whether the oscillatory changes of radio-sensitivity which occur within fractions of a second to a few minutes following flash irradiation correlate with an altered incidence of apoptosis, DNA strand breaks or lipid-coupled signalling. MATERIALS AND METHODS: Human tumor cells (SQ-20B, LoVo) or Chinese hamster V79 fibroblasts were exposed to split-dose, pulse irradiation with 3.5 MeV electrons at high dose-rate (12 or 120 Gy x s(-1)) and the effects assessed by clonogenic assays, analysis of DNA cleavage and microscopic observation. RESULTS: The processes underlying oscillatory radiation response were saturable, but did not correlate with an increased incidence of DNA single- or double-strand breaks or apoptosis. N-acetylcysteine and inhibitors of lipid-derived signalling also failed to alter oscillatory response. However, this response did correlate with phenotypic alterations evoking mitotic or delayed cell death. Furthermore, high dose-rate irradiation provided a lower level of instability than protracted gamma-ray irradiation. CONCLUSIONS: It is proposed that the early steps of DNA damage recognition and repair following priming radiation exposure bring about rapid, synchronous remodeling of chromatin, evoking enhanced chromosome damage upon re-irradiation.

[New administration modalities for radiotherapy in lung cancer]. / Les nouvelles modalités d'administration de la radiothérapie dans les cancers broncho-pulmonaires.

Much progress has been made in recent years in administration modalities for radiotherapy for lung cancer. Exposure time to external irradiation was the first parameter to be modified: hyperfractionated radiotherapy, hyperfractionated accelerated radiotherapy with or without concomitant irradiation, synchronous or asynchronous protocols, split course radiotherapy. Radiosensitizing agents have also been the subject of much research: radiosensitization of hypoxic cells, modifiers of the biological response, concomitant radiochemotherapy. The main drugs used are 5-fluorouracil, platinum salts, etoposide, hydroxyurea, taxanes, topotecan, vinorelbin, and gemcitabine. Outcome with these combinations is discussed, both for non-small-cell and small-cell lung cancer. 3D conformational radiotherapy can enable increased dosing in the tumoral target while better preserving healthy tissues. High dose endoluminal brachytherapy is used particularly as a palliative treatment for bronchial obstructions or as curative treatment for weakly infiltrative small endoluminal tumors.

Poly(ADP-ribose) polymerase, a major determinant of early cell response to ionizing radiation.

PURPOSE: To determine whether DNA-dependent protein kinase (DNA-PK) and poly(ADP-ribose) polymerase (PARP-1) are involved in eliciting the rapid fluctuations of radiosensitivity that have been observed when cells are exposed to short pulses of ionizing radiation. MATERIALS AND METHODS: The effect of DNA-PK and PARP-1 inhibitors on the survival of cells to split-dose irradiation was investigated using Chinese hamster V79 fibroblasts and human carcinoma SQ-20B cells. The responses of PARP-1 proficient and PARP-1 knockout mouse 3T3 fibroblasts were compared in a similar split-dose assay. RESULTS: Inactivation of DNA-PK by wortmannin potentiated radiation-induced cell kill but it did not alter the oscillatory, W-shaped pattern of early radiation response. In contrast, oscillatory radiation response was abolished by 3-aminobenzamide, a reversible inhibitor of enzymes containing a PARP catalytic domain. The oscillatory response was also lacking in PARP-1 knockout mouse 3T3 fibroblasts. CONCLUSION: The results show that PARP-1 plays a key role in the earliest steps of cell response to ionizing radiation with clonogenic ability or growth as endpoint. It is hypothesized that rapid poly(ADP-ribosylation) of target proteins, or recruitment of repair proteins by activated PARP-1 at the sites of DNA damage, bring about rapid chromatin remodelling that may affect the incidence of chromosomal damage upon re-irradiation.