Papers by Christian Carrie
Background: Considerable variation in intravenous 5-fluorouracil (5-FU) metabolism can occur due ... more Background: Considerable variation in intravenous 5-fluorouracil (5-FU) metabolism can occur due to the wide range of dihydropyrimidine dehydrogenase (DPD) enzyme activity, which can affect both tolerability and efficacy. The oral fluoropyrimidine tegafur-uracil (UFT) is an effective, well-tolerated and convenient alternative to intravenous 5-FU. We undertook this study in patients with locally advanced rectal cancer to evaluate the efficacy and tolerability of UFT with leucovorin (LV) and preoperative radiotherapy and to evaluate the utility and limitations of multicenter staging using pre-and post-chemoradiotherapy ultrasound. We also performed a validated pretherapy assessment of DPD activity and assessed its potential influence on the tolerability of UFT treatment.
This article was originally published in a journal published by Elsevier, and the attached copy i... more This article was originally published in a journal published by Elsevier, and the attached copy is provided by Elsevier for the author's benefit and for the benefit of the author's institution, for non-commercial research and educational use including without limitation use in instruction at your institution, sending it to specific colleagues that you know, and providing a copy to your institution's administrator. All other uses, reproduction and distribution, including without limitation commercial reprints, selling or licensing copies or access, or posting on open internet sites, your personal or institution's website or repository, are prohibited. For exceptions, permission may be sought for such use through Elsevier's permissions site at: http://www.elsevier.com/locate/permissionusematerial Abstract Objective. Attempts to increase survival in stage III ovarian cancer patients with minimal residual disease at second-look laparotomy have included consolidation radiotherapy. We present long-term survival of 106 consecutive patients treated between 1983 and 1993 in 4 French institutions for stage III ovarian adenocarcinoma with first-look debulking, cisplatin-based chemotherapy, second-look surgery with a residual disease < 1 cm and consolidation radiotherapy. Methods. Median age was 52 years. Residual disease after first look surgery was < 1 cm for 40.5% of patients. Median number of chemotherapy cycles was 6 (range 4–12). Residual disease < 1 cm at second-look laparotomy was observed in 79% of the patients, with 33% of patients in complete histologic remission. Residual disease < 1 cm was obtained in all patients after tumor excision during second-look surgery. Radiation was performed using a linear accelerator with a whole abdomen dose of 22.5 Gy, an additional 22 Gy pelvic boost for 71 patients, and an additional 12 Gy lombo-aortic boost for 33 patients. Results. Median follow-up was 14 years. Radiation was stopped for acute toxicity in 11 patients. Long-term toxicities included radiation enteritis in 21 patients with 9 patients requiring surgery for bowel obstruction. Four deaths were related to enteritis complications. Overall survival at 5 and 10 years was respectively 53% and 36%. Conclusion. This sequential treatment with final consolidation abdominopelvic radiotherapy is an effective treatment for a selected group of stage III ovarian cancer patients with a high intestinal toxicity incidence.
A B S T R A C T Purpose The effectiveness of nonsteroid topical agents for the prevention of acut... more A B S T R A C T Purpose The effectiveness of nonsteroid topical agents for the prevention of acute dermatitis during adjuvant radiotherapy for breast carcinoma has not been demonstrated., 254 patients who had been operated on for breast cancer and who were to receive postoperative radiation therapy were randomly allocated to application of either trolamine (128 patients) or calendula (126 patients) on the irradiated fields after each session. The primary end point was the occurrence of acute dermatitis of grade 2 or higher. Prognostic factors, including treatment modalities and patient characteristics, were also investigated. Secondary end points were the occurrence of pain, the quantity of topical agent used, and patient satisfaction. Results The occurrence of acute dermatitis of grade 2 or higher was significantly lower (41% v 63%; P .001) with the use of calendula than with trolamine. Moreover, patients receiving calendula had less frequent interruption of radiotherapy and significantly reduced radiation-induced pain. Calendula was considered to be more difficult to apply, but self-assessed satisfaction was greater. Body mass index and adjuvant chemotherapy before radiotherapy after lumpectomy were significant prognostic factors for acute dermatitis. Conclusion Calendula is highly effective for the prevention of acute dermatitis of grade 2 or higher and should be proposed for patients undergoing postoperative irradiation for breast cancer.
Background How best to treat rising prostate-specifi c antigen (PSA) concentration after radical ... more Background How best to treat rising prostate-specifi c antigen (PSA) concentration after radical prostatectomy is an urgent clinical question. Salvage radiotherapy delays the need for more aggressive treatment such as long-term androgen suppression, but fewer than half of patients benefi t from it. We aimed to establish the eff ect of adding short-term androgen suppression at the time of salvage radiotherapy on biochemical outcome and overall survival in men with rising PSA following radical prostatectomy.
Purpose: To evaluate the impact of transabdominal probe pressure on prostate positioning with an ... more Purpose: To evaluate the impact of transabdominal probe pressure on prostate positioning with an intramodality ultrasound (US) image-guided-radiotherapy system and to quantify pressure variability over the treatment course. Material and methods: 8 prostate cancer patients (group A) and 17 healthy volunteers underwent 3 consecutive US images with increasing probe pressure levels, and 1 CT acquisition for the group A only. Pros-tate positions were compared after manual registration of the first US image contour projected on 2 others. Group A's pressure levels were quantified by measuring skin-to-skin distances between corresponding CT–US images. The same methodology was used on paired CT/CBCT–US images acquired during treatments of 18 prostate cancer patients to determine whether the different pressure levels applied to the group A were close to the clinical practices and to quantify pressure variability along the treatment course. Results: 84% of 3D prostate displacements were above 2 mm for at least one pressure level. Probe pressures deliberately applied were similar to the ones observed clinically. The latter drastically varied between sessions. Conclusion: Even with an intramodality system, probe pressure can impact prostate localization because of the pressure variability along the treatment course. Therefore, margins should be expanded from 0.5 to 1.2 mm to ensure treatment accuracy.
Background. Since January, 1984, 59 children with histologically confirmed Ewing sarcoma of the p... more Background. Since January, 1984, 59 children with histologically confirmed Ewing sarcoma of the pelvic bone have been treated with three successive chemotherapy protocols recommended by the French Society of Pediatric Oncology. The purpose of the current study was to evaluate the role of surgery and/or radiotherapy in local progression-free, diseasefree, and overall survivals (LPFS, DFS, and OS, respectively). Procedure. We retrospectively examined 59 children treated for nonmetastatic, pelvic Ewing sarcoma over the last 12 years. All were first treated with chemotherapy according to the current French protocol. Six patients developed progressive disease before local treatment and were excluded for local control and survival analysis. Local treatment was surgery alone in 17 cases, radiation therapy in 27 cases, and surgery plus radiation therapy in 9 cases. Results. With a median of follow-up of 6.5 years, no significant differences in local control or survival were observed with the three chemotherapeutic protocols. Of the 53 patients evaluable for local control, 6 relapsed locally only, 8 had local and distant relapses, and 9 had distant metastases only. The 5-year OS rate was worst for patients with radiotherapy alone compared to those with surgery or combined modality treatment (44 % vs. 72 %, P = 0.043). The 5-year LPFS and DFS rates were worst in the radiotherapy-alone group but not significantly (63% vs. 79%, P = 0.22 and 42% vs 71%, P =0.07, respectively). The importance of surgery to OS and DFS was confirmed by multivariate analysis (P = 0.026 and P = 0.048, respectively). One surviving patient was diagnosed with in-field fibrosarcoma, which was presumably radiation induced. Conclusions. Despite intensive, multiagent chemotherapy, survival from pelvic Ewing sarcoma has not improved over the past decade; however, the survival rate does not seem to be worse than that from Ewing sarcoma at other locations, insofar as at least 50% of the patients were cured. Surgery or a combination of surgery and radiation therapy are the best local treatment; exclusive radiation therapy should be reserved for patients with inoperable lesions or partially or nonchemosensitive tumors or when surgery would be an amputation. Med.
A B S T R A C T Purpose To determine event free and overall survival, and long-term cognitive seq... more A B S T R A C T Purpose To determine event free and overall survival, and long-term cognitive sequelae of children with standard-risk medulloblastoma (SRM) treated with hyperfractionated radiotherapy, conformal reduced boost volume without chemotherapy, and online quality assurance. Patients and Methods Forty-eight patients (age 5 to 18 years) were included in the Medulloblastoma-Socié té Franç aise d'Oncologie Pé diatrique (MSFOP 98) protocol (December 1998 to October 2001). Patients received hyperfractionated radiotherapy (HFRT; 36 Gy, 1 Gy/fraction twice per day) to the craniospinal axis followed by a boost to the tumor bed (1.5-cm margin) to a dose of 68 Gy. Records of craniospinal irradiation were reviewed before treatment started. Neuropsychologic evaluations were done according to the protocol (1, 3, 5, and 7 years after irradiation). Cognitive outcomes were followed longitudinally with full-scale intelligence quotient (FSIQ) obtained with age-adapted Wechsler scales. Results After a median follow-up of 77.7 months, 6-year overall survival (OS) and event-free survival (EFS) rates for the cohort were 78% (95% CI, 66% to 90%) and 75%, respectively (95% CI, 62% to 87%). Thanks to quality control, 14 major deviations were detected. Annual full scale IQ decline was 2 points over a 6-year period. Predicted change in FSIQ points per year was 2.15 (95% CI, 1.24 to 3.51) with an intercept (ie, predicted FSIQ) of 93.57 at baseline. Conclusion HFRT protocol with conformal reduced boost and online quality control allows excellent long-term OS and EFS in the absence of chemotherapy. In addition, FSIQ drops seem to be less pronounced than previously reported with standard irradiation regimens.
Medulloblastoma spreads within the craniospinal ¯uid, and applying radiation therapy to the crani... more Medulloblastoma spreads within the craniospinal ¯uid, and applying radiation therapy to the craniospinal axis remains an important component of treatment. Many reports [1±4] show that the technical quality of the radiation therapy has an impact on the outcome of treatment. Insuf®cient coverage of the whole brain and menin-ges correlates with increased risk of local failure, especially in the region of the cribriform plate and the temporal lobe regions [5±7]. The advent of CT simulation and three-dimensional planning provides an opportunity to optimize coverage of the target. We have developed a simple but accurate method of producing customized blocks for the cranial ®elds. MATERIALS AND METHODS In the treatment of medulloblastoma, the patient is placed in the prone position with the head hyperextended. An immobilization device is used to minimize patient motion and setup errors. Planning CT with contrast is performed for the whole brain and the whole spine. The thickness of CT slices through the whole brain is 3 mm. The clinical target volume (CTV) is de®ned to be the whole cerebrospinal ¯uid pathway, and the whole brain and the spinal cord are contoured on the CT scan. Critical normal tissues including the lens are also contoured. Given estimated setup errors of 3±5 mm and penumbra (50 to 90% isodose curves) of approximately 7 mm, a margin of 10±12 mm was chosen as appropriate. A 1.1 cm margin was therefore added three-dimensionally around the contoured brain, and spinal cord and blocks were designed accordingly. Since the brain and spinal cord are easily identi®ed on the CT scan, the blocks generated using the above method should more easily assure adequate coverage of the inferior portions of the frontal and temporal lobes than those designed using bony landmarks. In order to determine the advantage, if any, of the above described technique, the blocks of a cohort of ÐÐÐÐÐÐ
Background How best to treat rising prostate-specifi c antigen (PSA) concentration after radical ... more Background How best to treat rising prostate-specifi c antigen (PSA) concentration after radical prostatectomy is an urgent clinical question. Salvage radiotherapy delays the need for more aggressive treatment such as long-term androgen suppression, but fewer than half of patients benefi t from it. We aimed to establish the eff ect of adding short-term androgen suppression at the time of salvage radiotherapy on biochemical outcome and overall survival in men with rising PSA following radical prostatectomy.
Purpose: The study aimed to determine the maximum tolerated dose of daily irinotecan given with c... more Purpose: The study aimed to determine the maximum tolerated dose of daily irinotecan given with concomitant radiotherapy in patients with locally advanced adenocarcinoma of the pancreas. Methods and Materials: Between September 2000 and March 2008, 36 patients with histologically proven unre-sectable pancreas adenocarcinoma were studied prospectively. Irinotecan was administered daily, 1 to 2 h before irradiation. Doses were started at 6 mg/m 2 per day and then escalated by increments of 2 mg/m 2 every 3 patients. Radiotherapy was administered in 2-Gy fractions, 5 fractions per week, up to a total dose of 50 Gy to the tumor volume. Inoperability was confirmed by a surgeon involved in a multidisciplinary team. All images and responses were centrally reviewed by radiologists. Results: Thirty-six patients were enrolled over a period of 8 years through eight dose levels (6 mg/m 2 to 20 mg/m 2 per day). The maximum tolerated dose was determined to be 18 mg/m 2 per day. The dose-limiting toxicities were nausea/vomiting, diarrhea, anorexia, dehydration, and hypokalemia. The median survival time was 12.6 months with a median follow-up of 53.8 months. The median progression-free survival time was 6.5 months, and 4 patients (11.4%) with very good responses could undergo surgery. Conclusions: The maximum tolerated dose of irinotecan is 18 mg/m 2 per day for 5 weeks. Dose-limiting toxicities are mainly gastrointestinal. Even though efficacy was not the aim of this study, the results are very promising, with a median survival time of 12.6 months.
Background and purposes: Early biomarkers of tumour response are needed to discriminate between r... more Background and purposes: Early biomarkers of tumour response are needed to discriminate between responders and non-responders to radiotherapy. We evaluated the ability of ceramide, a bioactive sphin-golipid, to predict tumour sensitivity in patients treated by hypofractionated stereotactic body radiation therapy (SBRT) combined with irinotecan chemotherapy. Materials and methods: Plasma levels of total ceramide and of its subspecies were measured before and during treatment in 35 patients with liver and lung oligometastases of colorectal cancer included in a phase II trial. Cer levels were quantified by LC–ESI-MS/MS and compared to tumour volume response evaluated one year later by CT-scan. Results: Pretreatment plasma ceramide levels were not indicative of tumour response. Nevertheless, the levels of total ceramide and of its 4 main subspecies were significantly higher at days 3 and 10 of treatment in objective responders than in non-responders. According to Kaplan–Meier curves, almost complete tumour control was achieved at 1 year in patients with increased total ceramide levels whereas 50% of patients with decreased levels experienced an increase in tumour volume. Conclusions: Total plasma ceramide is a promising biomarker of tumour response to SBRT combined with irinotecan that should enable to segregate patients with high risk of tumour escape. Ó 2016 Published by Elsevier Ireland Ltd. Radiotherapy and Oncology xxx (2016) xxx–xxx Radiation therapy is a common palliative and curative anti-cancer treatment but its efficacy is limited by intrinsic tumour resistance to radiation [1]. The development of stereotactic body radiation therapy (SBRT) has led to better tumour targeting and to the delivery of higher radiation doses in a limited number of fractions [2]. However, the efficacy of SBRT in reducing oligometas-tases and small solid tumours needs to be assessed for all tumours depending upon its resistance, size and location, usually by measuring tumour volume by non-invasive imaging techniques, such as CT-scan, MRI, or PET-scan. Since the response of the tumour is generally detected long after the end of radiotherapy, with late radiological modifications after SBRT being particularly difficult to assess [3], there is a real risk of prolonged unnecessary and ineffective exposure to radiation and of delays in initiating alternative treatments. The availability of biomarkers that distinguish between responding and refractory patients early during the course of radiotherapy would represent a major clinical advance to define patients with high risk of tumour escape to the treatment. A potentially interesting biomarker is ceramide (Cer), a pro-apoptotic sph-ingolipid generated rapidly after irradiation. Cer is produced in the outermost layer of the cell membrane on hydrolysis of sphin-gomyelin by acidic sphingomyelinase (ASM) or neutral sphin-gomyelinase (NSM) and is synthetized de novo in endoplasmic reticulum by Cer synthase [4]. Adding exogenous Cer to androgen-sensitive human prostate adenocarcinoma cells (LNCAP cells) enhanced cell radiosensitivity and tumour regression [5]. Increasing endogenous Cer in human T lymphocyte cells (Jurkat cells) by the action of inhibitors of glucosyl-Cer synthase and ceramidase inhibitors (DL-PDMP and D-MAPP, respectively) also enhanced cell radiosensitivity [6]. Cer induced by high dose
Background. Medulloblastoma is a rare disease in adult patients, with an annual incidence rate of... more Background. Medulloblastoma is a rare disease in adult patients, with an annual incidence rate of 0.05 per 100,000 per year. Results are, therefore, sparse and comprise small series over long periods. The real survival rate, the prognostic factors, the optimal postoperative radiation dose, and the role of adjuvant chemotherapy are still unknown for this disease in adults.
A CCD-based EPID using new crystal-assembly X-ray (CAX) converters is investigated for radiothera... more A CCD-based EPID using new crystal-assembly X-ray (CAX) converters is investigated for radiotherapy dosimetry. The proposed EPID design consists in replacing the common phosphor X-ray converters of current CCD-based EPIDs with high-stopping-power CAX converters. A Test Imaging Device (TID), consisting of a 30-mm-thick CAX converter made of Bismuth Germanate (BGO), coupled to a highly sensitive CCD camera, was used to evaluate the accessible imaging and dosimetric performance of the proposed design. The system response to dose and its dependence on photon beam energy were investigated. The effects of ghosting, dose rate, field size and phantom thickness were evaluated as well. The same measurements were also performed with our clinically used aSi-EPID so that comparisons of performance could be directly inferred. The TID displayed no detectable ghosting or sensitivity to dose rate. Its response to MU exposure was found to be linear within about AE1%. The level of glare induced in the TID and the aSi-EPID were equivalent. The TID resolution was higher than that of the aSi-EPID on the axis, but was found to decrease with off-axis distance. Finally, the image quality, assessed on the basis of signal-to-noise ratio in low dose radiographs of the larynx of a patient, was higher for the TID. The imaging performance accessible with the TID proved to be satisfying and its dosimetric capability was found to be superior to that of the current aSi-EPID.
Goal To retrospectively analyse all our elderly patients ([70 years old) treated with radiotherap... more Goal To retrospectively analyse all our elderly patients ([70 years old) treated with radiotherapy ± che-motherapy (RT ± CT) followed by brachytherapy (BRT) for anal canal cancer. Background Studies on clinical outcomes and toxicities of the standard treatments for anal canal cancers in elderly patients are rare and data are not homogeneous, so a standard of care cannot be defined for these patients. Study A retrospective analysis of efficacy and safety of RT ± CT followed by BRT has been performed. The impact of the modified Charlson Index and of other different clinical and therapeutic variables on these outcomes has been also studied. Results Seventy-six elderly patients with a histological diagnosis of anal canal cancer and with a median age of 76 years (range 70–88) were treated with a curative goal. Patients received radio-therapy alone (37/76, ''RT group'') or radiochemotherapy (39/76, ''RT–CT group''). All patients underwent a BRT boost. Five-year local control, overall survival, disease-specific survival, nodal progression-free survival and metastasis-free survival rates were 75.8, 75.8, 82.8. 87.8 and 89.0 %, respectively. Globally, the incidence of acute and late Grade 3–4 toxicities was 14.5 and 6.6 %, respectively. Only 2 patients received surgery because of severe ano-rectal toxicities. Any relationship between the modified Charlson Index and all the considered clinical outcomes was found. Conclusions Curative RT ± CT ? BRT showed an acceptable toxicity profile and a good efficacy also in elderly anal canal cancer patients and should be considered as an important therapeutic option also for these patients.
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Cancer/Radiothérapie
To analyse the process of outpatient radiation therapy by dividing it into elementary acts, and t... more To analyse the process of outpatient radiation therapy by dividing it into elementary acts, and to determine the cost-inducers (staff and machine time, equipment) in order to enhance the value of radiotherapy activity. The care process was analysed from 1 June 1997 to 1 September 1997, in two institutions (Centre hospitalo-universitaire de Saint Etienne and centre de Lutte contre le Cancer de Lyon), in terms of consumption of human and equipment means, representing a cost for the care institution. The valorization was expressed in physics units for material means, and in time units for human and heavy equipment. Parameters able to modify the consumption of means had been defined. The following data had been collected for each activity: patient characteristics, characteristics of the process, specific parameters of each activity, data related to the care staff and care unit. The importance of the specific data of each activity was noteworthy. Two criteria modified the valorization: t...
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Papers by Christian Carrie