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R J Bensadoun

Publications and source records attributed to R J Bensadoun.

At least 19 recordsLinked to original sources
PubMed2006

Monte Carlo simulation of a medical linear accelerator for radiotherapy use.

A Monte Carlo code MCNPX (Monte Carlo N-particle) was used to model a 25 MV photon beam from a PRIMUS (KD2-Siemens) medical linear electron accelerator at the Centre Antoine Lacassagne in Nice. The entire geometry including the accelerator head and the water phantom was simulated to calculate the dose profile and the relative depth-dose distribution. The measurements were done using an ionisation chamber in water for different square field ranges. The first results show that the mean electron beam energy is not 19 MeV as mentioned by Siemens. The adjustment between the Monte Carlo calculated and measured data is obtained when the mean electron beam energy is approximately 15 MeV. These encouraging results will permit to check calculation data given by the treatment planning system, especially for small fields in high gradient heterogeneous zones, typical for intensity modulated radiation therapy technique.

Body Burden↗
PubMed2005

[Propositions for the selection and the delineation of peritumoral microscopic disease volumes in oral cavity and oropharyngeal cancers (lymph nodes excluded)].

This article reviews the concept of selectivity in peritumoral microscopic disease to be included in the Clinical Target Volume (CTV) for elective treatment for oral cavity and oropharyngeal squamous cell carcinoma, using the local tumoral spread. The objective of the present article is to present a procedure for the delineation of the target volumes, required for an appropriate application of 3-DCRT and IMRT for head and neck cancers. These propositions are for the delineation of microscopic peritumoral target volumes when external beam irradiation is required. CTVs are illustrated on CT sections.

Carcinoma, Squamous Cell↗
PubMed2004

[Preliminary results of the assessment of intensity modulated radiotherapy (IMRT) for prostatic and head and neck tumors (STIC 2001)].

INTRODUCTION: Between May 2002 and May 2004, eight French comprehensive cancer centres did a prospective nonrandomized study including 200 patients, 100 with cancer of the prostate and 100 with head and neck cancers. Half of each patient group was treated by IMRT and the others by RTC 3D. This clinical study was associated with an economic study and a physics study. We report here the first results. PATIENTS AND METHODS: For the clinical study, the analysis of the data of the first 88 patients irradiated for a prostatic cancer shows that 39 received RTC and 49 IMRT with a mean dose of 78 Gy at the ICRU point at 2 Gy per fraction. For H&N tumours, the preliminary analysis was done on the 87 first patients with a mean follow-up of 11.5 months (2 to 25 months) and a median of 8.4 months for the IMRT groups and 13.2 months for the RTC group. The economic study was done on the first 157 patients included during the first 18 months: 71 treated by RTC (35 for H&N and 36 for prostate) and 86 treated by IMRT (38 for H&N and 48 for prostate). The assessment of the direct costs was realized by a micro-costing technique. The physical study compared dose distributions for both techniques and has created quality control recommendations. RESULTS: Clinical studies of the acute reactions do not show any difference between groups, but we want to point out the short follow-up and the relatively high dose delivered to cancers of the prostate. The physics study demonstrates that IMRT is technically feasible in good clinical conditions with high quality assurance, a good reproducibility and precision. Dosimetric data show that IMRT could certainly spare organs at risk more than RTC for H&N tumours. The direct costs of "routine" treatments for H&N tumours were 4922 euros for IMRT versus 1899 euros for RTC and for the prostatic cancers 4911 euros for IMRT versus 2357 for RTC.

Adolescent↗
PubMed2003

[Study of theoretical cases of intensity-modulated beams with step-and-shoot technique].

To initiate Intensity-Modulated Radiation Therapy (IMRT) in our department, theoretical cases were used as a training, to define methods of measurements and to verify the software by comparing results of calculation and measurement on a PMMA phantom. Irradiation was performed with 6 and 25 MV X-rays from a linear accelerator. For measurements, films and ionization chambers have been chosen. The comparison between calculations and measurements shows some discrepancies at the level of junctions and also in areas of low doses especially when many segments were used. These theoretical cases provide a first step on the way towards treatments with intensity modulation.

Bias↗
PubMed2003

[2003 update of Standards, Options and Recommandations for radiotherapy for patients with salivary gland malignant tumors (excluding lymphona, sarcoma and melanoma)].

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, which started in 1993, is a collaboration between the Federation of French Cancer Centers (FNCLCC), the 20 French Regional Cancer Centers. and specialists from French public universities,general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. OBJECTIVES: To update clinical practice guidelines for the management of patients with salivary gland malignant tumors previously validated in 1997. These recommendations cover diagnosis, treatment and follow-up of patients with these tumors. METHODS: The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts who define the CPGs according to the definitions of the Standards, Options and Recommendations project. Once the guidelines have been defined, the document is submitted for review by independent reviewers. RESULTS: This article presents the updated clinical practice guidelines concerning irradiation of patient with salivary gland tumors. The main recommendations are: 3 dimensional conformal radiotherapy (with or without intensity modulation) or 2D irradiation can be used; for surgical complete resected patients, postoperative photon radiotherapy should not be used in case of low grade stage I and 11 tumors(standard, level of evidence B2) but should be used for high grade stage II, II and IV tumors and for low grade stage III and IV tumors(standard, level of evidence B2). Neutron therapy should not be used in all of these cases (standard, level of evidence D); for patients presenting an incomplete macroscopic or microscopic surgical residual disease, postoperative irradiation must be delivered(standard). Neutron or photon therapy can be either delivered (options); for non operable patients neutron or photon therapy can be either delivered (options, level of evidence B2); for unresectable tumors or in case of recurrent neoplasms, exclusive neutron therapy or surgical tumor reduction combined with postoperative photon beam irradiation can be proposed (options, level of evidence C).

Combined Modality Therapy↗
PubMed2003

Pharmacokinetics of low-dose carboplatin and applicability of a method of calculation for estimating individual drug clearance.

BACKGROUND: Carboplatin is the only cancer drug for which conventional doses are individually adjusted according to estimated clearance and target area under the curve (AUC). The aim of this prospective study was (i) to evaluate intra- and interpatient variability of ultrafilterable (UF) carboplatin AUC(0-)(infinity) and (ii) to test whether the prediction of carboplatin clearance according to the Chatelut formula established for conventional carboplatin doses was accurate for low carboplatin doses. MATERIALS AND METHODS: Thirty-one head and neck cancer patients (29 men, two women, mean age 55.9 years) received concomitant radiotherapy (Rgamma 2 Gy/day) and chemotherapy (carboplatin 50 mg/m(2)/day i.v.) for 7 weeks: Rgamma was administered 5 days/week (days 1-5) and carboplatin 2 days/week (days 1 and 4). Pharmacokinetics was performed once per week. A limited sample strategy based on Bayesian analysis was first validated and blood was subsequently taken 1 and 4 h after the end of carboplatin administration. RESULTS: A total of 143 cycles was analyzed. Ultrafilterable carboplatin AUC(0-)(infinity) ranged from 0.360 to 4.200 mg.min/ml (mean 0.830, median 0.670). As a corollary, UF carboplatin clearance ranged from 19.1 to 244.7 ml/min. Ultrafilterable carboplatin concentrations were very stable over time: AUC(0-)(infinity) variability due to treatment duration contributed to <1% of the total variance, while interpatient variability contributed to 68.6%. Accordingly, intrasubject effect was not significant (P = 0.38) whereas intersubject effect was highly significant (P <0.001). These results suggest that optimal dosage for targeting a given AUC may vary within a 13-fold range between patients. The Chatelut formula, based on creatininemia, body weight, age and sex, over estimates carboplatin clearance by 40% on average (bias 95% CI 29.6% to 51.1%). No significant relationship was observed between either bone marrow toxicity or creatinine clearance decrease and carboplatin pharmacokinetics. CONCLUSIONS: The Chatelut carboplatin clearance model established for conventional carboplatin dosages (>100 mg/m(2)) is not applicable for targeting low AUC (<1 mg x min/ml).

Adult↗
PubMed2003

A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma.

The main objective of this prospective multicentre randomized phase III study was to compare a combined regimen of fotemustine plus whole brain irradiation with fotemustine alone in terms of cerebral response and time to cerebral progression in patients with melanoma cerebral metastases. Seventy-six patients were randomized to receive either fotemustine (arm A, n = 39) or fotemustine plus whole brain irradiation (arm B, n = 37). Fotemustine was administered intravenously at 100 mg/m(2) on days 1, 8 and 15, followed by a 5 week rest period, then every 3 weeks in non-progressive patients. In arm B, concomitant whole brain irradiation was performed at a total dose of 37.5 Gy (2.5 Gy/day on days 1-5 for three consecutive weeks). Although patients who received fotemustine alone had worse prognostic factors, there was no significant difference in cerebral response (arm A, 7.4%, arm B, 10.0%) or control rates (objective responses plus stable disease) after 7 weeks (arm A, 30%; arm B, 47%) or in overall survival (arm A, 86 days; arm B, 105 days). However, there was a significant difference in favour of arm B for the time to cerebral progression (P = 0.028, Wilcoxon test). In conclusion, fotemustine plus whole brain irradiation delayed the time to cerebral progression of melanoma cerebral metastases compared with fotemustine alone but without a significant improvement in terms of objective control or overall survival.

Adult↗
PubMed2003

Validation of intensity modulation on a commercial treatment planning system.

For two years now, a study on intensity modulated radiotherapy (IMRT) has been in progress at the Antoine Lacassagne Hospital Center for Cancer Therapy (in Nice) in collaboration with the University of Nice-Sophia Antipolis. The kind of intensity modulation that was used is the "step and shoot" technique in which the modulated beam is created both by adding andjoining elementary fields. Before carrying out clinical tests, several problems regarding the production of modulated beams has to be mastered. The current developments of our study enable us to dosimetrically produce (in water phantom and in the PMMA phantom) complexmodulated whose segmentation was calculated by one commercial treatment planning system (TPS). Nevertheless, we showed and studied some critical discrepancies between standard clinical calculations and the calculations using field segmentation. We showed that with nonoptimal conditions of segmentation the discrepancies, which are due to the type of algorithm used, could bring about significant errors inside the field of up to 10% of maximum dose. Another point of our study is the quantification and resolution of differences between measurements and calculations due to the internal segmentation of calculated modulated fields and their realization on Linac. Once again, in none optimal conditions of segmentation and inside the field we obtained discrepancies up to 20% of maximum dose between calculations using field segmentation and measurements. That was mainly due to the tongue and groove effect and penumbra phenomena. This study allows us to show that the discrepancies between segmentation calculations and standard clinical calculations should be solved by the use of penumbra models during segmentation calculations. We will introduce both the study and its near-future perspectives.

Algorithms↗
PubMed2003

[Intensity modulated radiotherapy (IMRT) in France: The boost of the national funding for the new expensive innovative technologies (STIC 2001 and 2002)].

The STIC 2001 and STIC 2002 projects intend to allow the implementation and the assessment of Intensity Modulated Radiation Therapy in France. IMRT is an innovative technique in which the high-dose radiation volume conforms to an accurately defined target volume with less morbidity to the surrounding normal tissues. The main medical objectives of the projects are (1) to improve the therapeutic index while decreasing acute toxicity and late sequelae (mainly xerostomia and acute mucite for head and neck tumors), which allows an increase in the radiation dose to the tumor and then a better tumor control; (2) to propose a salvage treatment to patients who locally recurred in previously irradiated sites; (3) to determine the optimal treatment guidelines for a safe use of the technique in clinical routine. Our projects also aim at comparing IMRT and 3D conformal treatments on the one hand (STIC 2001), and IMRT and conventional treatments on the other hand (STIC 2002), with regard to costs. As a matter of fact, the use of IMRT is presently limited in France because its implementation requires high investment and personnel costs. The seventeen French Regional Cancer Centres involved in the two projects intend to study the additional cost of the use IMRT in comparison with the use of standard techniques, which appears to be a step for a wide use of this technique in France. Each of the studies is two-year prospective, and includes patients with head and neck tumors treated with a curative intend (post operative or exclusive treatments for STIC 2002 and STIC 2002), and patients with a prostate cancer (STIC 2001).

Adult↗
PubMed2001

Concomitant twice-a-day radiotherapy and chemotherapy in unresectable head and neck cancer patients: A long-term quality of life analysis.

BACKGROUND: The purpose of this study is to make a comparative analysis between acute toxicity with late toxicity. This study is based upon a French quality of life (QoL) questionnaire in a cohort of advanced head and neck (H&N) cancer patients treated by concomitant twice-a-day continuous radiotherapy with no acceleration and chemotherapy with cisplatin and 5-fluorouracil. METHODS: From September 1992 to November 1997, a prospective data bank of 91 patients was constituted. In November 1999, 31 patients were still alive and followed for more than 3 years. All patients had stage IV strictly unresectable squamous cell carcinoma of oropharynx or hypopharynx. A French specific H&N cancer QoL questionnaire was used at the end of radiotherapy and at the last date of follow-up of each patient (during 1999). p values reflect comparison of percentages obtained at the end of treatment with percentages at long-term follow-up. Statistical analysis was performed using chi(2) test (p <.05 considered as significant). Percentages obtained by the QoL questionnaire correspond to moderate-severe problems only. RESULTS: Twenty-nine of 31 (94%) patients participated in the QoL study. Acute treatment toxicities were severe with declines in virtually all QoL and functional domains. Globally, with an average long-term follow-up of 4.5 years (range 3-7 years after treatment), there is a statistical improvement in the following symptoms: dry mouth and sticky saliva (97% versus 55%, p <.05); tasting problems (35% versus 21%, not significant); swallowing problems (77% versus 36%, p <.05); and H&N pain (86% versus 9%, p <.05). Financial problems were not improved (21% versus 14%, not significant), and psychological problems (59% versus 5%) were statistically significant. Fourteen of 29 (48%) patients were drinking and 8 of 29 (28%) were smoking at long-term follow-up; at the diagnosis they were 86% and 90%, respectively. At long-term follow-up 22 of 29 presented good or very good QoL, and 25 of 29 said they had improved their initial QoL. CONCLUSION: The interest of twice-a-day radiotherapy with concomitant chemotherapy is to increase total radiotherapy equivalent dose without increasing late toxicity and also to improve locoregional control, survival, and long-term QoL/effectiveness ratio. Best supportive care is recommended to obtain both good QoL and cancer control in a long-term follow-up.

Adult↗
PubMed2001

Comparison between nasogastric tube feeding and percutaneous fluoroscopic gastrostomy in advanced head and neck cancer patients.

Wasting is a major complication of advanced head and neck cancer and the aim of this study was to compare nasogastric tube feeding (NG) and percutaneous fluoroscopic gastrostomy (PFG) in these patients. The goal of these two methods of nutritional support was to improve or maintain the initial nutritional status during treatment. A total of 90 patients, all stage IV oropharynx or hypopharynx tumor, were reviewed from a prospective databank. All these patients were treated by concomitant chemotherapy and twice-daily continuous radiotherapy with no acceleration. Fifty patients were managed by PFG, and the rest by NG. Mechanical failure, duration of feeding, complications, nutritional evaluation and quality of life were analysed. Mechanical failure occurred in 32 of the 40 NG patients and in seven of the gastrostomy group. In the PFG group, 80% of patients conserved their nutritional support after the end of the radiotherapy, none patient in the NG group. In the PFG group, two presented a wound infection and six had aspiration pneumonia while in the NG group, 21 had aspiration pneumonia probably due to the NG tube (gastroesophageal reflux). The feeding methods were found to be equally effective at maintaining body weight and body mass index at time 1 (3 weeks) and at time 2 (6 weeks). Advantages were associated with PFG cosmesis, mobility and quality of life. PFG is a safe and effective method of providing enteral nutrition during treatment to patients with advanced head and neck cancer and offers important advantages over NG.

Administration, Cutaneous↗
PubMed2001

Chemotherapy- and radiotherapy-induced mucositis in head and neck cancer patients: new trends in pathophysiology, prevention and treatment.

Mucositis is the intensity-limiting toxicity in the management of locally advanced non-resectable head and neck cancer with radiotherapy and chemotherapy. New radiation modalities (hyperfractionation and/or acceleration) as well as combined modality regimens in this situation induce higher rates of acute toxicity. Hyperfractionation, for example, allows higher control rates, with few late toxicities, but it slightly increases acute mucositis. The addition of chemotherapy introduces systemic toxicity and can exacerbate local tissue reactions when used concurrently with radiotherapy. Mucositis is recognized as the principal limiting factor to further treatment intensification. As local regional control and overall survival are related to dose-intensity in this case, further research into the assessment, analysis, prevention and treatment of mucosal toxicity is not only crucial to improvement in quality of life, but certainly also to improved rates of disease control. Several topical and systemic treatments are directed to the decrease and the acceptance of this acute toxicity, but few have shown a significant preventive effect. The efficacy of low-level laser therapy in the management of such toxicity could hence yield important developments with this method in the field of oncology.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

The relationship of epidermal growth factor receptor levels to the prognosis of unresectable pharyngeal cancer patients treated by chemo-radiotherapy.

The aim of this study was to analyse prognostic factors for time to treatment failure (TTF) and overall survival (OS) in patients with unresectable cancer of the pharynx. A twice daily (b.i.d.) radiotherapy with concomitant cisplatin-5-fluorouracil chemotherapy was administered to 77 consecutive patients (68 males, 9 females; median age: 56 years). The studied factors were: age, gender, tumour differentiation, tumour volume, initial hemoglobin level, karnofsky index (KI), primary tumour location, T, N, epidermal growth factor receptor (EGFR) level in the tumour (fmol/mg protein). KI and EGFR level were significant predictors in a multivariate analysis for TTF (P=0.004 and P=0.0001) and OS (P=0.004 and P=0.0001). In order to select subgroups with different outcomes, a stratification of patients was performed based on the EGFR value: patients with tumour EGFR levels <35 fmol/mg protein, between 35 and 275 fmol/mg protein and >275 fmol/mg protein had 95%, 51% and 16% 3 year OS rates, respectively (log rank test; P=0.0001). Interestingly, for patients exhibiting a complete response (CR) after concomitant b.i.d. chemo-radiotherapy, patients with EGFR levels <35 fmol/mg protein were all alive at 3 years; in contrast, there was only 70 and 13% 3 year survival rates for patients with EGFR tumour levels between 35 and 275 fmol/mg protein and above 275 fmol/mg protein, respectively. EGFR determination appears to be a powerful prognostic parameter in unresectable pharyngeal cancer patients treated by concomitant chemo-radiotherapy.

Adult↗
PubMed2001

[Concomitant bifractionated radiotherapy and chemotherapy with cisplatin and 5-fluorouracil in locally progressive, non-resectable epidermoid carcinomas of the pharynx: ten years experience at the Antoine Lacassagne center].

PURPOSE: Patients suffering from locally advanced unresectable squamous cell carcinoma of the oropharynx and hypopharynx treated with radiotherapy alone have a poor prognosis. More than 70% of patients die within 5 years mainly due to local recurrences. The aim of this study was to evaluate retrospectively the Antoine Lacassagne Cancer Center's experience in a treatment by concomitant bid radiotherapy and chemotherapy. Evaluation was based on analysis of the toxicity, the response rates, the survival, and the clinical prognostic factors. PATIENTS AND METHODS: From 1992 to 2000, 92 consecutive patients were treated in our single institution. All of them had stage IV, unresectable squamous cell carcinoma of the pharynx and they received continuous bid radiotherapy (two daily fractions of 1.2 Gy, 5 days a week, with a 6-h minimal interval between fractions). Total radiotherapy dose was 80.4 Gy on the oropharynx and 75.6 Gy on the hypopharynx. Two or three chemotherapy courses of cisplatin (CP)-5-fluorouracil (5FU) were given during radiotherapy at 21-day intervals (third not delivered after the end of the radiotherapy). CP dose was 100 mg/m2 (day 1) and 5-FU was given as 5-day continuous infusion (750 mg/m2/day at 1st course; 430 mg/m2/day at 2nd and 3rd courses). Special attention was paid to supportive care, particularly in terms of enteral nutrition and mucositis prevention by low-level laser energy. RESULTS: Acute toxicity was marked and included WHO grade III/IV mucositis (89%, 16% of them being grade IV), WHO grade III dermatitis (72%) and grade III/IV neutropenia (61%). This toxicity was significant but manageable with optimised supportive care, and never led to interruption of treatment for more than 1 week, although there were two toxic deaths. Complete global response rate at 6 months was 74%. Overall global survival at 1 and 2 years was 72% and 50% respectively, with a median follow-up of 17 months. Prognostic factors for overall survival were the Karnofsky index (71% survival at 3 years for patients with a Karnofsky index of 90-100% versus 30% for patients with a Karnofsky index of 80% versus 0% for patients with a Karnofsky index of 60-70%, p = 0.0001) and tumor location (55% at 3 years for oropharynx versus 37% for panpharynx versus 28% for hypopharynx, p = 0.009). CONCLUSION: These results confirm the efficacy of concomitant bid radiotherapy and chemotherapy in advanced unresectable tumor of the pharynx. The improvement in results will essentially depend on our capacity to restore in a good nutritional status the patients before beginning this heavy treatment.

Adult↗
PubMed2001

Clinical prognostic factors for patients with recurrent head and neck cancer: implications for randomized trials.

The purpose of our study was to determine the clinical prognostic factors for the duration of the overall survival from recurrence (OSR) in patients with recurrent head and neck squamous-cell carcinoma. We performed a retrospective analysis on 496 patients treated between 1982 and 1993 at the Antoine Lacassagne Center. The significant favorable prognostic factors for the OSR were: initial T(1-2) (p = 0.008), no initial nodal involvement (p = 0.002), no initial chemotherapy exposure (p = 0.002), induction chemotherapy response (p = 0.001), duration of disease-free interval (DFI; p = 0.0001), performance status (PS) 0-1 (p = 0.004) and local-regional recurrence (p = 0.001). In the multivariate analysis, the apparent nonsignificance of all factors apart from the DFI suggested that relevant prognostic factors could be embedded in the DFI. Multivariate analysis was performed after excluding the DFI. The results indicated that local-regional recurrence, PS 0-1 and no initial chemotherapy exposure remained significant favorable prognostic factors for the OSR. The advantages of taking into account such prognostic factors are to eliminate the patient selection bias and to ensure a fairer comparative evaluation of new or already existing agents in recurrent head and neck cancer.

Adult↗
PubMed2000

Systematic percutaneous fluoroscopic gastrostomy for concomitant radiochemotherapy of advanced head and neck cancer: optimization of therapy.

Wasting is a major complication of advanced head and neck cancer. Concomitant chemotherapy and twice-daily continuous radiotherapy with no acceleration represents a promising treatment modality for these tumors, but increases the risk of mucositis. This report describes the results achieved with percutaneous fluoroscopic gastrostomy (PFG) and its impact on the quality of life of patients with head and neck cancer in terms of their nutritional status. A total of 50 stage IV tumors of the oropharynx and hypopharynx recorded in a prospective database were reviewed retrospectively. All patients were managed by PFG, which was found to be a safe and effective technique with no technical failures. PFG feeding resulted in a mean increase in body weight of 2.5 kg within 3 weeks. The body mass index (BMI) was maintained at 3 and 6 weeks. Minor complications occurred, but no major complications were noted. The overall procedure-related mortality rate was nil. Further prospective investigations are necessary to determine whether treatment of wasting improves patient survival.

Adult↗