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Summary Purpose In the ACOSOG Z0011 trial, patients with primary breast cancer and 1–2 tumor-involved sentinel lymph nodes (SLNs) undergoing breast-conserving surgery had no oncological outcome benefit after axillary lymph node dissection (ALND), despite a relevant rate of non-SLN metastases of 27%. According to the St Gallen expert consensus, and NCCN and ASCO clinical guidelines, ALND may be avoided in patients who meet all ACOSOG Z0011 inclusion criteria. This recommendation can also be extended to patients undergoing mastectomy, with 1 or 2 positive SLNs and an indication for chest wall radiation, in whom axillary radiotherapy can be proposed as an alternative to completion ALND. The aim of this study was to assess non-compliance with the NCCN and ASCO clinical guidelines and Z0011 criteria, namely the rate of performance of completion ALND when it was not recommended, and the rate of failure to perform completion ALND when recommended. Methods Data were prospectively analysed from T1-2 N0 breast cancer patients undergoing an SLN procedure and treated at the Georges-Francois Leclerc Cancer Center between November 2015 and May 2017. Factors associated with non-compliance treatment decisions were identified using logistic regression. Results Among 563 patients included, 122 (21.7%) had at least one positive SLN. ALND was not recommended for 76 patients (62.3%), and was recommended in 46 patients (37.7%). The rate of non-compliant treatment was 32% (39/122) overall: ALND was performed despite not being recommended in 16/76 patients (21.1%) and was not performed in 50% of patients in whom it was recommended (23/46). By multivariate analyses, lymphovascular invasion ((Odds Ratio (OR) = 6.1; 95% confidence interval (CI): 1.4-26.7; P = 0.02)) and only one SLN removed (OR = 9.1; 95%CI: 2.2-33.3; P = 0.002) were associated with performance of completion ALND when not recommended. Conversely, >1 SLN removed (OR = 5.1; 95%CI: 1.2-22.2; P = 0.03) was associated with the failure to perform completion ALND when recommended. Conclusion Almost one third of patients with invasive breast cancer receive treatment that is not in compliance with recommendations regarding completion ALND.

Primary vaginal cancers are rare tumours, for which external beam radiotherapy and brachytherapy are major treatment tools. Given the complexity of brachytherapy techniques, the treatment should be performed in specialised centres. We present the recommendations of the French society for radiation oncology on the indications and techniques for external beam radiotherapy and brachytherapy for primary vaginal cancer.

PURPOSE To describe the quality assurance (QA) program and early toxicities in the phase III randomized trial BONBIS (NCT00907868) on the role of a localized radiation boost in ductal carcinoma in situ (DCIS). MATERIALS AND METHODS From November 2008 to July 2014, 2004 patients were randomized in arm A (only whole breast radiotherapy, WBRT) and arm B (WBRT + boost). The QA program involved 44 participant centers that performed the dummy run (DR). Compliance and uniformity of clinical target volume (CTV) delineations, and dose prescription and delivery according to the BONBIS trial radiotherapy guidelines were analyzed. Acute toxicities (during and up to 3 months after radiotherapy completion, NCI-CTCAE v3.0 classification) were evaluated in 1929 patients. RESULTS The differences in whole breast CTV (CTV1) and planning target volume (PTV1) were ≤10%, and the differences in boost CTV (CTV2) and PTV (PTV2) were ≥20% compared with the reference DR values; 95% of the prescribed dose encompassed 98.7% and 100% of the median CTV1 and CTV2. Grade ≥2 breast erythema (38.3% vs. 22.4% of grade 2 and 5.4% vs. 2.1% of grade 3, p

This section highlights selected specific new recommendations and/or updates that have been published during the very last years in the fields of stereotactic radiotherapy, pediatrics, lung cancer, gynecologic and breast cancer, as well as in the area of radiation oncology of urogenital cancer.

External beam radiotherapy and brachytherapy are major treatments in the management of cervical cancer. For early-stage tumours with local risk factors, brachytherapy is a preoperative option. Postoperative radiotherapy is indicated according to histopathological criteria. For advanced local tumours, chemoradiation is the standard treatment, followed by brachytherapy boost, which is not optional. We present the update of the recommendations of the French Society of Oncological Radiotherapy on the indications and techniques for external beam radiotherapy and brachytherapy for cervical cancer.

The first intent upfront treatment of endometrial cancer is surgery. External radiotherapy and brachytherapy; however, are important tools in adjuvant setting, according to histopathological risk factors for locoregional recurrence or in the event of an inoperable tumor. We present the update of the recommendations of the French society of oncological radiotherapy on the indications and technical methods of performing radiotherapy and brachytherapy for endometrial cancer.

Primary vulvar carcinomas are rare gynaecological cancers, for which surgery is the mainstay of treatment. There is however a major place for external beam radiotherapy in the situation of inoperable locally advanced tumours and/or as adjuvant therapy, when there are risk factors for locoregional relapse. We present the recommendations of the French society for radiation oncology on the indications and techniques for radiotherapy in the treatment of primary vulvar cancer.

Pancreatic cancer has poor prognosis and a continuously growing incidence. By 2030, it should become the second cause of death by cancer worldwide and in France. The only curative treatment is surgery that is achievable in only 20% of patients at the time of initial diagnosis, with a high rate of incomplete resection. Neoadjuvant treatments using chemotherapy with or without radiotherapy are more often admitted to play an important role by selecting non-progressing cases who will benefit from surgery, by increasing the number of complete resection, and by making locally advanced and borderline tumours accessible to resection. However, the role of radiotherapy is still debated. Because of its dosimetric advantages, its short total duration, and its good tolerance with reduced volumes of irradiation, stereotactic radiotherapy has been largely studied. Compared to chemoradiotherapy, this technique could improve the therapeutic index helping to preserve the general status of patients in order to give them access to secondary surgery. It remains a promising technique still under evaluation, to be delivered ideally, as part of a clinical trial, or within an experimented team.

The management of myeloid and lymphoid disease is essentially based on chemotherapy and targeted therapies. Since radiotherapy could be responsible for severe late toxicities, essentially due to conventional bidimensional irradiation techniques, many trials have attempted to omit radiotherapy or to scale down the dose in their therapeutic strategy. Nevertheless, radiotherapy still plays a role for curative or symptomatic purposes.

We present the results of the PHRC Tridicol, a prospective French phase II study whose objective was to increase the dose delivered to the target volume during brachytherapy for locally advanced cervical cancers.Eight centers included 48 patients, treated with concomitant radiochemotherapy, then uterovaginal brachytherapy.The median follow-up was 63 months. The dose of brachytherapy delivered in biological equivalent dose (EQD2) to 90% of the High Risk CTV (D90 CTV HR) was 80Gy in median dose. The 5-year local control rate (LC) was 84%, close to the hypothesis of 86.7%. The rate of severe complications (grade 3-4) was 23% at 5 years. The rectal dose was correlated with the risk of severe complications.HR CTV dose was below the target (85Gy) due to low use of parametrial interstitial needles, as the centers did not always have an adequate applicator, or were at the time at the beginning of their learning curve. The 5-year LC rate was improved compared to that of the comparable STIC PDR group (78%) but lower than the retroEMBRACE cohort of GEC ESTRO (89%). The complication rate was higher than in the comparable group of STIC PDR but close to that of retroEMBRACE. Training brachytherapy teams in interstitial implantation or referring patients to referral centers should help improve the therapeutic index of cervical cancer.

Stereotactic lung radiosurgery has been carried out in the team at the Georges-François-Leclerc centre (CGFL) in Dijon since 2008 on a Truebeam® accelerator (Varian®) with the RPM technique.Fifty patients with primary T1-T2 stage lung cancer (n=30) or lung metastasis (n=20) were included in the study. Since 2014, 3 successive 4D scanners on D1, D2 and D3, have been produced in order to ensure the reproducibility of ITV (Internet Target Volume). The 3 ITVs are contoured (ITV 1, 2 and 3) from the MIP (Maximum Intensity Projection) of each of the 3 scanners. A global ITV is created from the ITV volumes of the 3 scanners (MIP 2 and 3 merged with MIP 1). A CBCT (Cone Beam Computerised Tomography) is performed at the start of each irradiation session to position the patient. The study consisted in analysing the relevance of the realisation of 3 different scanners before dosimetry to define the ITV and in comparing the volumes contoured on the different CBCT to the ITV to make sure that the tumour volume is well included in the ITV during the sessions.There is a strong correlation between the different ITVs 1, 2, 3 and global, as well as between the volumes obtained on the different CBCTs. The correlation coefficient between the different ITVs and the volumes contoured on CBCT was high for upper lobar lesions. In terms of tolerance, the FEV1 (Maximum volume expired during the first second) did not seem to be a significant factor influencing the correlation between the ITV and the volumes bypassed on CBCT.Performing a single 4D planification CT is sufficient to consider stereotactic lung irradiation, regardless of the location of the lung lesions. The correlation coefficient between ITV and CBCT was high for upper lobar lesions.

Purpose To determine the 3 years late toxicity among patients with non-metastatic breast cancer who received concurrent bevacizumab and locoregional radiotherapy. Material and methods This is a single-arm, multicentre, prospective study, of the toxicity of adjuvant concomitant association of bevacizumab and radiotherapy in patients with breast cancer. Toxicity was assessed by the Common Terminology Criteria for Adverse Events version 3.0 during the radiotherapy and follow-up clinics at 12 and 36 months after its completion. The study was designed to evaluate the toxicity at one year, 3 years and 5 years. Results Sixty-four patients were included from October 2007 to August 2010. All of them received concurrent adjuvant radiotherapy and bevacizumab (in 24 cases after primary systemic treatment). All patients received non-fractionated radiotherapy to breast or chest wall with or without irradiation of regional lymph nodes. Early toxicity has been previously reported. Median follow-up was 46.4 months (range: 18–77 months). Median age was 53 years old (range: 23–68 years). The 3-years overall survival was 93% (range: 87–100%). Evaluation of the toxicity at 3 years was available for 67% of the patients. There was a low rate of toxicity: 14% grade 1 pain, 9% grade 1 fibrosis, 2% grade 1 telangiectasia, 2% grade 1 paresis, 7% grade 1 lymphedema and 2% grade 3 lymphedema. No grade 4 toxicity was observed. No patient had a left ventricular ejection fraction below 50% at 3 years. Conclusions Concurrent bevacizumab with locoregional radiotherapy is associated with acceptable 3-years toxicity in patients with breast cancer.

Background and purposeFew data are available concerning the safety of bevacizumab (B) in combination with locoregional radiation therapy (RT). The objective of this study was to evaluate the 5-year late toxicity of concurrent B and RT in non-metastatic breast cancer.Materials and methodsThis multicentre prospective study included non-metastatic breast cancer patients enrolled in phase 3 clinical trials evaluating B with concurrent RT versus RT alone. All patients received neoadjuvant or adjuvant chemotherapy and normofractionated breast or chest wall RT, with or without regional lymph node RT. B was administered at an equivalent dose of 5 mg/kg once a week for 1 year. The safety profile was evaluated 1, 3 and 5 years after completion of radiotherapy.ResultsA total of 64 patients were included between November 2007 and April 2010. Median follow-up was 60 months (12-73) and 5-year late toxicity data were available for 46 patients. The majority of tumours were triple-negative (68.8%), tumour size ConclusionConcurrent B and locoregional RT are associated with acceptable 5-year toxicity in patients with non-metastatic breast cancer. No grade ≥3 toxicity was observed.

Purpose The present study evaluated the outcomes of concurrent weekly docetaxel and platinum-based drug doublet in association with concurrent thoracic radiotherapy (TR) in the curative treatment of stage III locally advanced non-small-cell lung cancer (NSCLC). Patients and Methods Patients with stage IIIA/B NSCLC were retrospectively included. Patients received weekly docetaxel and either cisplatin or carboplatin intravenous injections during concurrent TR (60 to 66 Gy). Patients who received induction chemotherapy with the same drug doublet were also included. The endpoints were: disease control rate (DCR), overall recurrence rate, survival rates [disease-free survival (DFS) and overall survival (OS)] and toxicity. Results Eighty-nine consecutive patients treated with this association were included. Median follow-up time was 57.8 months. DCR was 76.5% at the first follow-up CT scan (6 to 12 weeks after the end of concurrent treatment). Median DFS and OS was 14.3 and 29.9 months respectively. Three-year survival was 43%. The overall recurrence rate was 65.9%. During overall treatment, grade 3 to 4 adverse events occurred in 29.2% of patients, the most common being esophagitis (12.4% of patients). Only 13.5% of patients presented with a grade 3 or higher adverse event after the end of concurrent treatment. Conclusions Weekly docetaxel and platinum-based drug doublet combined with TR yielded promising results in stage III NSCLC, with high survival rates. The toxicity of this association is acceptable, with mainly manageable esophagitis. These findings warrant validation in a prospective study before considering this association for standard of care.

Purpose: EGFR is frequently overexpressed in cervical cancer, suggesting EGFR blockade as a promising treatment approach. Cetuximab, an anti EGFR antibody, used conjointly with radiochemotherapy, was feasible in first-line treatment of cervix carcinoma limited to the pelvis. Experimental Design: This randomized phase II trial enrolled 78 FIGO stage IB2–IIIB cervical cancer patients to either cisplatin-based radiochemotherapy alone (arm B, n = 38) or conjointly with a 6-week course of weekly cetuximab (arm A, n = 40). Brachytherapy was given to the pelvic mass. Primary endpoint was disease-free survival (DFS) at 2 years. EGFR expression and targeted sequencing were performed in 54 of 78 patients. Results: Cetuximab over a 6-week period did not improve DFS at 24 months. At 31 months median follow-up, DFS was not significantly different (P = 0.18). Complete response at 4 to 6 months was strongly predictive for excellent DFS (log-rank test; P < 0.001). PIK3CA, KRAS, and STK11 mutations were observed in 22%, 4%, and 2% of patients, respectively. No tumor with a PI3K pathway mutation showed complete response (0/8 in arm A and 0/6 in arm B), whereas 14 of 52 (27%) tumors without mutations did (P = 0.021). PI3K pathway-mutated tumors showed a trend toward poorer DFS (P = 0.06) following cetuximab (8/22) as compared with those following standard treatment only (6/18). Conclusions: Similar to patients with head and neck cancer, patients with cervical cancer showed no gain in DFS at 2 years following a combined treatment of cetuximab with radiochemotherapy. Although treatment tolerance and compliance were satisfactory, it remains to be demonstrated whether maintenance therapy with cetuximab could be beneficial in selected patient groups. Clin Cancer Res; 21(11); 2530–7. ©2015 AACR.

External irradiation and brachytherapy still have a major place in the treatment of cervix and endometrial carcinoma. This review presents the French guidelines in terms of preparation and choice of irradiation techniques of these gynecological malignancies.

Preoperative chemoradiation (P-CRT) remains a controversial strategy in the treatment of squamous cell cancer (SCC) and adenocarcinoma (ADC) of the oesophagus. Until recently, randomised studies mixed the two, often without any distinction. In randomised studies involving exclusively SCC, P-CRT increases the rate of local control, R0 resection, pCR and disease-free survival. The absence of any impact on overall survival may be linked to the toxic effects of this treatment. Meta-analyses have revealed a survival benefit of approximately +13% at 2 years. However, the methodology used was perhaps questionable. Five randomised trials involving ADC patients compared P-CRT with surgery alone. The results were contradictory with insufficient statistical power in selected positive studies to answer this issue once and for all. P-CRT is unsatisfactory as a standard treatment. Although local control rates were increased with P-CRT, it should be considered only for selected patients in selected centres.

Purpose To compare the impact of an unilateral post-operative irradiation or a bilateral irradiation in terms of loco-regional control and survival in patients with cervical lymph node of squamous cell carcinoma from an unknown primary (CUP). Methods and materials Ninety five patients with epidermoid carcinoma involving unilateral cervical lymph nodes from an unknown primary were treated in two institutions from 1990 to 2007. Post-operative radiation therapy was delivered to one side of the neck in 59 cases, to both sides of the neck in 36 cases. There were 11 women and 84 men ranging in age from 38 to 80years (median 59years). Neck dissection was performed in 79 patients while 16 patients underwent single lymph node sampling only. Results After a median follow-up of 3.3years, the nodal relapse rate was 34% after unilateral neck irradiation and 25% after bilateral radiotherapy ( p =0.21). Six contralateral lymph node relapses occurred after unilateral irradiation (10%). The 5-year overall survival rate of the entire group was 24%. The 5-year OS rates were 22% after unilateral irradiation and 23%, after bilateral radiotherapy ( p =0.944). The occult primary occurred in 12% after unilateral irradiation and 6% after bilateral radiotherapy. The radiation technique (3D-CRT or IMRT vs. 2D: p =0.026) was prognostic on loco-regional control. Independent prognostic determinants on overall survival were the WHO status ( p =0.013) and the radiation technique (2D vs.3D-CRT or IMRT; p =0.029). There was no difference in loco-regional control ( p =0.639) and no difference in survival ( p =0.493) when chemotherapy was associated. Conclusions Retrospective comparisons between bilateral and unilateral neck radiotherapies did not show differences in terms of loco-regional control and survival. However, patient's local regional control and survival are significantly improved after 3D-CRT or IMRT.

Background Monocentric cohorts suggested that radiation-induced CD8 T-lymphocyte apoptosis (RILA) can predict late toxicity after curative intent radiotherapy (RT). We assessed the role of RILA as a predictor of breast fibrosis (bf +) after adjuvant breast RT in a prospective multicenter trial. Methods A total of 502 breast-cancer patients (pts) treated by conservative surgery and adjuvant RT were recruited at ten centers. RILA was assessed before RT by flow cytometry. Impact of RILA on bf + (primary endpoint) or relapse was assessed using a competing risk method. Receiver–operator characteristic (ROC) curve analyses were also performed in intention to treat. This study is registered with ClinicalTrials.gov, number NCT00893035 and final analyses are presented here. Findings Four hundred and fifty-six pts (90.8%) were included in the final analysis. One hundred and eight pts (23.7%) received whole breast and node irradiation. A boost dose of 10–16 Gy was delivered in 449 pts (98.5%). Adjuvant hormonotherapy was administered to 349 pts (76.5%). With a median follow-up of 38.6 months, grade ≥ 2 bf + was observed in 64 pts (14%). A decreased incidence of grade ≥ 2 bf + was observed for increasing values of RILA (p = 0.012). No grade 3 bf + was observed for patients with RILA ≥ 12%. The area under the ROC curve was 0.62. For cut-off values of RILA ≥ 20% and, Highlights • High value of radiation-induced lymphocyte apoptosis (RILA) was clearly associated with no risk of severe toxicities. • RILA is done rapidly (72 h) and from a single blood sample without any tissue biopsy. • RILA will change the practice and has to be integrated in multivariate models to optimize the evaluation of the risk. Of original research, some reports from our group focused on the development of the radiation-induced lymphocyte apoptosis assay. High values of this test were shown to be correlated with the absence of late effect after curative intent radiotherapy. For breast cancer, surgery and immediate reconstruction could be offered instead of conserving-surgery and radiotherapy. Reduced volume as in partial breast radiotherapy could also be proposed in the case of low-risk tumors to protect healthy tissues without carcinologic risk. In addition, low values of this test will be arguments against breast reconstruction. If no alternatives are available new radiotherapy techniques have to be considered.

To assess toxicity profile in two stage-IB1 cervical cancer treatment strategies: surgery with and without preoperative uterovaginal pulsed dose-rate brachytherapy.A retrospective study included 45 patients presenting stage-IB1 cervical cancer without pelvic lymph-node invasion, between 2009 and 2011: 25 treated by colpohysterectomy alone (group A) and 20 with preoperative uterovaginal pulsed dose-rate brachytherapy (group B). The median follow-up was 45 and 39 months (group A and B).Groups were comparable for age (median, 46.9 vs 47.6 years), histologic type (52% vs 65% squamous cell carcinoma) and tumor size (68% vs 60%,2cm). In postoperative year 1, rates of urinary, digestive and gynaecological disorder were 39.1%, 8.7% and 15% respectively in group A versus 36.8%, 5.3% and 31.6% in group B and in year 2, 5.9%, 8.4% and 15% versus 5.6%, 5.1% and 27.8%.The present study comparing two stage-IB1 cervical cancer treatment strategies found no significant difference in early or late complications. In 2 months, there was greater grade-3 urinary toxicity (21.1%) and sexual disorder (15.8%) with preoperative brachytherapy but no significant difference. Exclusive surgery is probably preferable for the patient's quality of life.

The purpose of this multicenter prospective and descriptive study was to determine late toxicities and outcomes among patients with non-metastatic breast cancer receiving concurrent bevacizumab (BV) and radiation therapy (RT) in the clinical trials. Early and late toxicities were assessed and evaluation was available for 63 patients (pts) at 12 months. Acute radiation dermatitis was observed in 48 (76%): grade 1 for 27, grade 2 for 17 and grade 3 for 4 pts. Grade 2 acute oesophagitis was observed in one patient (2%). Little toxicity was described 1 year after the completion of RT: 7 pts (12%): grade 1–2 pain, 3 (5%) presented grade 1 fibrosis, and 2 pts (4%) – telangiectasia. One patient (2%) experienced grade 1 dyspnoea. Five grade 1–2 lymphoedema occurred. Only one patient experienced a LEVF value less than 50% one year after the end of RT. In conclusion , the concurrent BV with locoregional RT provides acceptable toxicities.

Introduction To investigate the dosimetric impact of daily on-line repositioning during a full course of IMRT for prostate cancer. Materials and methods Twenty patients were treated with image-guided IMRT. Each pre-treatment plan (Plan A) was compared with a post-treatment plan sum (Plan B) based on couch shifts measured. The delivered dose to the prostate without a daily repositioning was inferred by considering each daily couch shift during the whole course of image-guided IMRT (i.e. plan B). Dose metrics were compared for prostate CTV (P-CTV) and PTV (P-PTV) and for organs at risk. Ten patients were treated with a 5 mm margin and 10 patients with a 10 mm margin. Results For plan A vs plan B: the average D95, D98, D50, D mean and EUD were: 76.4 Gy vs 73.9 Gy (p = 0.0007), 75.4 Gy vs 72.3 Gy (p = 0.001), 78.9 Gy vs 78.4 Gy (p = 0.014), 78.7 Gy vs 77.8 Gy (p = 0.003) and 78.1 Gy vs 75.9 Gy (p = 0.002), respectively for P-CTV, and 73.2 Gy vs 69.3 Gy (p = 0.0006), 70.7 Gy vs 66.0 Gy (p = 0.0008), 78.3 Gy vs 77.5 Gy (p = 0.001), 77.8 Gy vs 76.4 Gy (p = 0.0002) and 74.4 Gy vs 69.2 Gy (p = 0.003), respectively for P-PTV. Margin comparison showed no differences in dose metrics between the two plans except for D98 of the rectum in plan B which was significantly higher with a 10 mm margin. Conclusions The absence of daily image-guided IMRT resulted in a significantly less uniform and less homogeneous dose distribution to the prostate. A reduction in PTV margin showed neither a lower target coverage nor a better spare of OAR with and without daily image-guided IMRT.

Purpose This is a phase I, escalating-dose trial targeting exclusively patients with non-small cell lung cancer (NSCLC), investigating pemetrexed and fixed-dose cisplatin concurrently administered with high-dose radiotherapy (RT) after induction chemotherapy (CT). Primary objective was to determine the maximum tolerated dose and recommended phase II dose of pemetrexed. Patients and Materials Patients with unresected stage III NSCLC, planned V20 ≤ 35%, and FEV ≥ 1.3 L, were treated every 21 days for 2 cycles (pemetrexed 500 mg/m 2 ; cisplatin 75 mg/m 2 ), followed by 2 cycles of concurrent CT-RT: pemetrexed starting dose was 400 mg/m 2 , escalated up to 800 mg/m 2 per 100 mg/m 2 dose level (DL), cisplatin at 75 mg/m 2 and RT at fixed dose of 66 Gy/33 fractions. Results Nine of 10 enrolled patients (age range 46–68 years; 6 men; ECOG PS 0 [6 patients], PS 1 [4] ; stage IIIA [1] , IIIB [9] ; 6 adenocarcinomas, 3 squamous cell carcinomas, 1 large cell carcinoma) were entered on 3 DLs. Dose escalation of pemetrexed was conducted up to 600 mg/m 2 based on the independent safety monitoring board recommendation. One dose-limiting toxicity occurred at DL3: Grade 4 septic shock. Grade 3 related toxicities: 2 neutropenia at DL3, 2 lymphopenia per DL (3 recurrent), 2 leukopenia (1 recurrent) at DL3, 1 gastric pain (DL3), 1 nausea and 1 recurrent vomiting (DL2). No Grade 3/4 radiation-related toxicities were observed. No toxic death was observed. Disease control rate was 77.7% (1 CR, 4 PR, 2 SD). One-year survival rate was 90%. Conclusions This phase I report of pemetrexed is dedicated to NSCLC with induction therapy and fixed high-dose RT. Pemetrexed at 500 mg/m 2 , concurrently given with cisplatin and RT was well tolerated and appears to be the only third-generation agent that can likely be recommended safely at full dose in future trials with concurrent RT.

Our study aims at evaluating the cost of pulsed dose-rate (PDR) brachytherapy with optimized dose distribution versus traditional treatments (iridium wires, cesium, non-optimized PDR). Issues surrounding reimbursement were also explored.This prospective, multicentre, non-randomised study conducted in the framework of a project entitled "Support Program for Costly Diagnostic and Therapeutic Innovations" involved 21 hospitals. Patients with cervix carcinoma received either classical brachytherapy or the innovation. The direct medical costs of staff and equipment, as well as the costs of radioactive sources, consumables and building renovation were evaluated from a hospital point of view using a microcosting approach. Subsequent costs per brachytherapy were compared between the four strategies.The economic study included 463 patients over two years. The main resources categories associated with PDR brachytherapy (whether optimized or not) were radioactive sources (1053euro) and source projectors (735euro). Optimized PDR induced higher cost of imagery and dosimetry (respectively 130euro and 367euro) than non-optimized PDR (47euro and 75euro). Extra costs of innovation over the less costly strategy (iridium wires) reached more than 2100euro per treatment, but could be reduced by half in the hypothesis of 40 patients treated per year (instead of 24 in the study).Aside from staff, imaging and dosimetry, the current hospital reimbursements largely underestimated the cost of innovation related to equipment and sources.

Most endometrial cancers are diagnosed at stage I (disease limited to the uterine corpus). The definitive treatment for endometrial carcinoma consists in total abdominal hysterectomy and bilateral salpingo-oophorectomy with or without lymphadenectomy. The decision of adjuvant treatment depends on risk factors. Postoperative radiotherapy plays a major role in the management of stage I endometrial cancer but the respective place of external radiotherapy and vaginal brachytherapy remains controversial. Adjuvant external beam radiotherapy reduces locoregional recurrences, but carries a risk of toxicity without overall survival benefits. Recent data suggest that vaginal brachytherapy is effective in preventing vaginal recurrence with lower toxicity and should be the treatment of choice for intermediate risk endometrial cancer.

At cellular level, signalization pathway activated by ErbB receptors participate to the proliferation, migration and differenciation of many cellular types. Observed alterations are mutations, overexpressions with or without gene amplification or abnormal stimulation by their ligands. The most frequently observed mutation is an extracellular deletion aiming to activate tyrosine kinase activity without ligand. Strategies to target the EGFr receptor include antisens oligonucleotids, antibodies directed to extracellular component of tyrosine kinase receptor. Only monoclonal antibodies and TKI have been developed in clinical research, mainly for oesophageal and rectal carcinomas. Solid tumor proliferation is under control of tumoral mechanisms and the interaction between tumor and microenvironment. In particular, angiogenesis is important during invasive and metastasis phases. The major role of Vasculoendothelial Growth Factor (VEGF) in angiogenesis is useful for tumor growth, which has been demonstrated by many convergent studies. Radiosensitivation or reversion of radioresistance could be obtained by inhibition of VEGF pathway. Antibodies directed against this molecule have been introduced in GI tract malignancies for the treatment of pancreatic and colic carcinomas.

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Tomotherapy is a new external beam radiation therapy technique using helicoidal intensity modulated radiation principle. It is able to avoid multiple isocenters requested to irradiate large volumes. This machine integrates image acquisition, treatment planning, positioning of the patient and irradiation into a sole engine. Six degrees of freedom robot coupled with a 6 MV linear accelerator, InCA has installed the Cyberknife in France in 3 sites chosen. The last generation of linac is a multifunction machine able to deliver conformal irradiations with or without intensity modulated radiation therapy, cranial or extracranial stereotactic irradiation with or without arctherapy or modulation. Performances of each machine have to be measured and compared in a medical and economical procedure.

Summary Purpose We performed a retrospective analysis in order to eva-luate the compliance with preoperative radiotherapy in patients aged ≥70 with locally advanced resectable rectal cancer, and to evaluate the influence of comorbidities on treatment tolerance and oncological results. Methods From March 1984 to December 2000, 95 patients with T3-T4 N0 M0 rectal cancer received a preoperative radiotherapy in 2 radiotherapy departments. Nineteen patients received concomitant chemotherapy. Results All patients completed the radiation schedule. Six patients suffered grade 3 acute WHO toxicity. Surgical resection was performed in 87 patients. There were 3 post-operative deaths. Analysis of peri-operative complications showed thromboembolism (4.9%), ileus (9.8%) and diarrhoea (6.1%). After a median follow-up of 29 months, the 3- and 5-year overall survival rates were 65% and 49% respectively. In univariate analysis, a tumour located in the mid part of the rectum, a radiation dose less than 40 Gy, the absence of chemotherapy were significantly associated with a poor prognosis. There was a trend to a better survival for patients with a Charlson score of 0 (P=0.0584). In multivariate analysis, only initial WHO performance status was significant. Conclusions Compliance with preoperative radiotherapy is good in elderly patients. Toxicity rates are similar to those described in randomised trials in which only younger patients were included. Initial WHO performance status ≤1 is significantly associated with better survival.

Optically guided ultrasound imaging has been used in our department since 2003 in order to implement an on line correction scheme in intensity modulated radiation therapy of prostate carcinoma.The corrections observed during the initial time period of the system (17 patients) are compared to those observed more recently (10 patients). Treatment margins are calculated.Overall systematic errors decreased between 2003 and 2006, and are presently statistically not different from zero. Random errors remain the same (max 4.3 mm). Proposed margins are 7 mm both in lateral and longitudinal direction and 8.4 mm in anteroposterior.Ultrasound can be used for on line correction of both positioning and internal organs motion errors and allows reduction of the margins between clinical and planning volume.

The Sonarray ultrasound system is a non-invasive technique allowing real-time prostate localization. Since 2003, it has been used in our department before intensity modulated radiation therapy for prostate cancer. We reported both setup errors and organ motion detected by Sonarray system and the accuracy of this ultrasound imaging dedicated to radiotherapy.

Conformal radiation therapy with or without intensity modulation is the standard treatment of localized prostate cancer and facilitates dose escalation. The implementation of three-dimensional conformal radiotherapy necessitates focusing on target volume delineation, dosimetry, reproducibility of treatment and quality control. Recently, ultrasound systems that allow direct daily visualization of the prostate have become available. This non-invasive technique can be used to correct both prostate organ motion and set-up error and leads to increase treatment accuracy.

Conformal radiation therapy has now to be considered as a standard treatment of localized prostatic adenocarcinomas. Using conformational methods and intensity modulated radiation therapy requires a rigorous approach for their implementation in routine, focused on the reproducibility of the treatment, target volume definitions, dosimetry, quality control, setup positioning. In order to offer to the largest number of patients high-dose treatment, the clinicians must integrate as prognostic factors accurate definition of microscopic extension as well as the tolerance threshold of critical organs. High-dose delivery is expected to be most efficient in intermediary risks and locally advanced diseases. Intensity modulated radiation therapy is specifically dedicated to dose escalation. Perfect knowledge of classical constraints of conformal radiation therapy is required. Using such an approach in routine needs a learning curve including the physicists and a specific quality assurance program.

Constraint definitions in intensity modulated radiation therapy is a key point factor during the treatment planning process. In literature some data are available about dose constraints and volumes according to the tissue architectures. Following ICRU recommendations, organs at risk organized in a parallel structure could receive an acceptably small proportion of high dose component. Mean dose and dose volume histogram is a most convenient tool for incorporating such constraints. Organs described as a serial structure are supposed to receive less than the given maximum dose, directly linked to the occurrence of complications. Dmax is the best way to describe such events. These constraints are new tools in radiation therapy, available for optimizing the dose distribution in target volume, sparing the organs at risk to protect the organ function or at least decreasing the late functional damages like xerostomia. It is necessary to define with accuracy gross target volumes and clinical target volume with available radio-anatomical guidelines before introducing current constraints on each volume in the inverse dosimetry. The management of these constraints remains under the responsibility of the clinicians. A permanent compromise has to be chosen between homogeneity of the dose distribution in the target volume and the probability of preserving functions of organs at risk.

Early glottic carcinomas can be treated with radiotherapy or surgery with similar local control rates but with better functional results with radiotherapy. The aim of this study was to analyze the results of our experience of exclusive radiotherapy.From 1975 to 2001, 155 patients with Tis, T1 and T2 glottic carcinomas were treated with exclusive radiotherapy. Prognostic factors of survival, local control and larynx-preservation rates were analyzed in uni and multivariate analyses.Median prescribed dose was 65 Gy in 44 days. Overall survival was 75% for the whole group, 75% for Tis, 85% for T1a, 72% for T1b, 59% for T2. Specific survival was 88% for the whole group, 75% for Tis, 94% for T1a, 90% for T1b, 69% for T2. Disease-free survival was 68% for the whole group, 75% for Tis, 77% for T1a, 51% for T1b, 58% for T2. Laryngeal preservation rate was 85% (133/155). Twenty-nine (29/155, 18%) patients developed a local relapse within 31 months. Out of the 10/86 (12%) T1a-Tis relapses, 7/10 patients underwent total laryngectomy and 79/86 larynx were preserved (92%). Out of the 8/22 (36%) T1b relapses, 4/8 patients underwent total laryngectomy. Out of the 11/47 (23%) T2 relapses, 8/11 patients underwent total laryngectomy. Increased overall treatment time, tumor stage, sub-glottis extension were associated with poorer local control. Second malignancies remain a major problem in the outcome of this population.Radiotherapy remains an efficient option in the treatment of early glottic carcinomas providing a high local control rate with excellent functional results in laryngectomy-free patients. This strategy should be discussed according to the tumor stage, feasibility of conservative surgery and patient's preferences.