Search

Purpose: The surrogacy of biochemical recurrence (BCR) for overall survival (OS) in localized prostate cancer remains controversial. Herein, we evaluate the surrogacy of BCR using different surrogacy analytic methods., Materials and Methods: Individual patient data from 11 trials evaluating radiotherapy dose escalation, androgen deprivation therapy (ADT) use, and ADT prolongation were obtained. Surrogate candidacy was assessed using the Prentice criteria (including landmark analyses) and the two-stage meta-analytic approach (estimating Kendall's tau and the R 2 ). Biochemical recurrence-free survival (BCRFS, time from random assignment to BCR or any death) and time to BCR (TTBCR, time from random assignment to BCR or cancer-specific deaths censoring for noncancer-related deaths) were assessed., Results: Overall, 10,741 patients were included. Dose escalation, addition of short-term ADT, and prolongation of ADT duration significantly improved BCR (hazard ratio [HR], 0.71 [95% CI, 0.63 to 0.79]; HR, 0.53 [95% CI, 0.48 to 0.59]; and HR, 0.54 [95% CI, 0.48 to 0.61], respectively). Adding short-term ADT (HR, 0.91 [95% CI, 0.84 to 0.99]) and prolonging ADT (HR, 0.86 [95% CI, 0.78 to 0.94]) significantly improved OS, whereas dose escalation did not (HR, 0.98 [95% CI, 0.87 to 1.11]). BCR at 48 months was associated with inferior OS in all three groups (HR, 2.46 [95% CI, 2.08 to 2.92]; HR, 1.51 [95% CI, 1.35 to 1.70]; and HR, 2.31 [95% CI, 2.04 to 2.61], respectively). However, after adjusting for BCR at 48 months, there was no significant treatment effect on OS (HR, 1.10 [95% CI, 0.96 to 1.27]; HR, 0.96 [95% CI, 0.87 to 1.06] and 1.00 [95% CI, 0.90 to 1.12], respectively). The patient-level correlation (Kendall's tau) for BCRFS and OS ranged between 0.59 and 0.69, and that for TTBCR and OS ranged between 0.23 and 0.41. The R 2 values for trial-level correlation of the treatment effect on BCRFS and TTBCR with that on OS were 0.563 and 0.160, respectively., Conclusion: BCRFS and TTBCR are prognostic but failed to satisfy all surrogacy criteria. Strength of correlation was greater when noncancer-related deaths were considered events.

Purpose: Radiation therapy is often the last resource treatment for cervical relapse in iodine refractory differentiated thyroid cancer. We present locoregional control data in patients with cervical relapse treated with curative intent radiation therapy with or without concomitant carboplatin., Material and Methods: This monocentric retrospective study gathered data on patients with differentiated thyroid carcinoma - vesicular or papillary - in relapse after thyroidectomy who received a curative intent cervical radiation therapy. Locoregional progression free survival (LRPFS), progression free survival (PFS), overall survival (OS) were gathered as well as acute and chronic adverse events assessed with the CTCAE v4., Results: Thirty-nine patients were consecutively included between 2005 and 2019. The median follow-up was 36.6months. Fifteen patients (38%) had a locoregional relapse, locoregional control at 2years was 66.7%. The median LRPFS was 48months [32.9-not reached] and the median overall survival 49months [38.8-not reached]. In multivariate analysis, initial incomplete resection was associated with poorer OS (HR: 24.39 [3.57-166.78], P=0.00113) and LRPFS (HR: 33.91 [4.46-257.61], P=0.00066), extra nodal spread was associated with poorer LRPFS (HR: 13.45 [1.81-99,76], P=0.011). ECOG performance status was associated with OS (HR: 5.11 [1.57-16.66], P=0.00688). Carboplatin association with radiation therapy was not associated with improved survivals (OS: P=0.34, LRPFS: P=0.84). The rate of acute grade 3 toxicities was 14%., Conclusion: Salvage cervical radiation therapy was associated with a locoregional control of 66.7% at 2years with a reasonable toxicity rate. Carboplatin association with radiation therapy did not improve locoregional control nor overall survival in comparison with radiotherapy alone., (Copyright © 2021. Published by Elsevier Masson SAS.)

The nasal cavity and parasinusal cancer are rare (10% of tumors of the head and neck) and are mainly represented by squamous cell carcinoma of the nasal cavity or the maxillary sinus and adenocarcinoma of the ethmoid sinus (occupational disease, wood dust). The most common clinical sign is nasal obstruction, but tumors can also manifest as rhinorrhea and/or epistaxis (usually unilateral signs). A magnetic resonance imaging of the facial structure is systematic for staging before treatment. The treatment consists of a first surgery if the patient is operable with a resectable tumor. If it is not the case, the treatment consists of radiotherapy (RT) associated with chemotherapy (CT) according to the initial data (T3/T4 or N+). After first surgery, RT is indicated (except T1N0 with complete resection) associated with a CT based on postoperative data (capsular effraction or incomplete resection). Lymph node irradiation is considered case by case, but is indicated in any nodal involvement. RT must be an intensity modulated RT (IMRT), static or dynamic, and must be imagery guided (IGRT). According to ICRU 83, doses to organs at risk and target volumes must be carried. Finally, after a post-treatment baseline imaging between 2 and 4 months, monitoring will be alternated with the ENT surgeon every 2 or 3 months for 2 years, then every 4 to 6 months for 5 years., (Copyright © 2016 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Esophageal cancer has a high likelihood of distant lymphatic spread even at an early stage. Radiotherapy plays a major role in the management of localized or locally-advanced esophageal cancer with a regional or distant lymph node involvement. Radiotherapy can sterilize micrometastatic nodes and cancer cells in transit in the peri-esophageal fat that are not removed by surgery. After preoperative chemoradiotherapy followed by monobloc esophagectomy including lymph node dissection above and below the diaphragm, the locoregional failure rate was around 3% in the Chemoradiotherapy for Esophageal Cancer followed by Surgery Study Group (CROSS) trial. This is significantly lower than that observed with surgery alone or following exclusive chemoradiotherapy delivering 50 Gy over 5 weeks. Patterns of failure usually combine local and nodal failure. These results suggest that: (1) radiotherapy plays a major role in the management of micrometastatic nodes that are not removed by surgery; (2) the total dose of radiotherapy without surgery may be too low to control macroscopic disease. Better knowledge of regional failure sites and the enhancement of clinical practices through homogenized nodal radiotherapy could lead to a decrease in regional relapses, but at the expense of irradiated volumes greater than the macroscopic tumor volume. Intensity-modulated radiotherapy or volumetric modulated arctherapy makes it possible to increase mediastinal irradiated volumes while effectively protecting healthy tissues., (Copyright © 2014 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Background: EORTC trial 22921 examined the addition of preoperative or postoperative chemotherapy to preoperative radiotherapy in patients with rectal cancer. After a median follow-up of 5 years, chemotherapy-irrespective of timing-significantly improved local control. Adjuvant chemotherapy did not improve survival, but the Kaplan-Meier curves diverged, suggesting possible delayed benefit. Here, we report the updated long-term results., Methods: We randomly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy with or without concomitant chemotherapy before surgery followed by either adjuvant chemotherapy or surveillance. Randomisation was done using minimisation with factors of institution, sex, T stage, and distance from the tumour to the anal verge. Study coordinators, clinicians, and patients were aware of assignment. Radiotherapy consisted of 45 Gy to the posterior pelvis in 25 fractions of 1·8 Gy over 5 weeks. Each course of chemotherapy consisted of fluorouracil (350 mg/m(2) per day intravenous bolus) and folinic acid (leucovorin; 20 mg/m(2) per day intravenous bolus). For preoperative chemotherapy, two courses were given (during weeks 1 and 5 of radiotherapy). Adjuvant chemotherapy was given in four cycles, every 3 weeks. The primary endpoint was overall survival. This analysis was done by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00002523., Findings: 1011 patients were randomly assigned to treatment between April, 1993, and March, 2003 (252 to preoperative radiotherapy and 253 to each of the other three groups). After a median follow-up of 10·4 years (IQR 7·8-13·1), 10-year overall survival was 49·4% (95% CI 44·6-54·1) for the preoperative radiotherapy group and 50·7% (45·9-55·2) for the preoperative radiotherapy and chemotherapy group (HR 0·99, 95% CI 0·83-1·18; p=0·91). 10-year overall survival was 51·8% (95% CI 47·0-56·4) for the adjuvant chemotherapy group and 48·4% (43·6-53·0) for the surveillance group (HR 0·91, 95% CI 0·77-1·09, p=0·32). 10-year disease-free survival was 44·2% (95% CI 39·5-48·8) for the preoperative radiotherapy group and 46·4% (41·7-50·9) for the preoperative radiotherapy and chemotherapy group (HR 0·93, 95% CI 0·79-1·10; p=0·38). 10-year disease-free survival was 47·0% (95% CI 42·2-51·6) for the adjuvant chemotherapy group and 43·7% (39·1-48·2) for the surveillance group (HR 0·91, 95% CI 0·77-1·08, p=0·29). At 10 years, cumulative incidence of local relapse was 22·4% (95% CI 17·1-27·6) with radiotherapy alone, 11·8% (7·8-15·8) with neoadjuvant radiotherapy and chemotherapy, 14·5% (10·1-18·9) with radiotherapy and adjuvant chemotherapy and 11·7% (7·7-15·6) with both adjuvant and neoadjuvant chemotherapy (p=0·0017). There was no difference in cumulative incidence of distant metastases (p=0·52). The frequency of long-term side-effects did not differ between the four groups (p=0·22)., Interpretation: Adjuvant fluorouracil-based chemotherapy after preoperative radiotherapy (with or without chemotherapy) does not affect disease-free survival or overall survival. Our trial does not support the current practice of adjuvant chemotherapy after preoperative radiotherapy with or without chemotherapy. New treatment strategies incorporating neoadjuvant chemotherapy are required., Funding: EORTC, US National Cancer Institute, Programme Hospitalier de Recherche Clinique, Ligue contre le Cancer Comité du Doubs., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Protracted preoperative radiochemotherapy with a 5-FU-based scheme, or a short course of preoperative radiotherapy without chemotherapy, are the standard neoadjuvant treatments for resectable stage II-III rectal cancer. Local failure rates are low and reproducible, between 6 and 15% when followed with a "Total Mesorectal Excision". Nevertheless, the therapeutic strategy needs to be improved: distant metastatic recurrence rates remain stable around 30 to 35%, while both sphincter and sexual sequels are still significant. The aim of the present paper was to analyse the ongoing trials listed on the following search engines: the Institut National du Cancer in France, the National Cancer Institute and the National Institute of Health in the United States, and the major cooperative groups. Keywords for the search were: "rectal cancer", "preoperative radiotherapy", "phase II-III", "preoperative chemotherapy", "adjuvant chemotherapy" and "surgery". Twenty-three trials were selected and classified in different groups, each of them addressing a question of strategy: (1) place of adjuvant chemotherapy; (2) optimization of preoperative radiotherapy; (3) evaluation of new radiosensitization protocols and/or neoadjuvant chemotherapy; (4) optimization of techniques and timing of surgery; (5) place of radiotherapy for non resectable or metastatic tumors., (Copyright © 2011 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

Purpose: To evaluate the efficacy and toxicity of high-dose-rate (HDR) brachytherapy in patients with inoperable endobronchial carcinoma., Methods and Materials: We retrospectively reviewed the records (April 1991-May 2004) of patients with non-small-cell carcinoma, with no extrabronchial spread on computed tomography scans, who underwent HDR brachytherapy because of contraindications to surgery and external beam radiation therapy. Kaplan-Meier survival curves were compared by the log-rank test. Prognostic factors were analyzed by multivariate analysis., Results: 226 patients (223 men, 3 women, mean age: 62.2 years (range, 40-84)) were included. Of those, 217 (97%) had squamous cell carcinoma (Tis/T1/T2/Tx: 60/153/9/4). Dose was prescribed at 1 cm from the radius (24-35 Gy in 4-6 fractions). Mean follow-up was 30.4 months (range, 9-116). Complete endoscopic response rate was 93.6% at 3 months. One hundred twenty-eight patients (56%) died of intercurrent disease (n = 45), local failure (n = 36), metastasis (n = 10), local failure and metastasis (n = 11), complications (n = 13), and other causes (n = 12). The 2-year and 5-year survival rates were, respectively, 57% and 29% (overall) (median, 28.6 months), 81% and 56% (cancer-specific), and 68% and 50% (local disease-free). Acute toxicity included pneumothorax (1.5%) and mucosal inflammation (10%). Late complications were hemoptysis (6.6% with 5% of fatalities), bronchitis (19.5%), and necrosis (3.5%). In multivariate analysis, a distal tumor location and the use of two catheters were associated with improved local disease-free survival (p = 0.003 and p = 0.007, respectively) and a distal tumor location with improved overall survival (p = 0.0001)., Conclusions: This large retrospective study confirms that HDR brachytherapy is an efficient and safe treatment in patients with inoperable endobronchial carcinoma., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Purpose: Few studies have evaluated the quality of life (QoL) of patients with rectal cancer. This report describes the quality of life of French patients who entered the 22921 EORTC trial that investigated the role and place of chemotherapy (CT) added to preoperative radiotherapy (preop-RT)., Patients and Methods: Patients without recurrences were evaluated with EORTC QLQ-C30 and QLQ-CR38 questionnaires, after a median time of 4.6 years from randomisation., Results: All the scores of QLQ-C30 functions were high, from 78 up to 88, with those of global health quality of life scale (GHQL) status being 73. The mean scores of symptoms were low except for diarrhoea. For QLQ-CR38, the mean scores for "body image" and "future perspective" were high at 79.6 and 69.7 respectively. The scores for "sexual functioning" and "enjoyment" were low. Men had more sexual problems than females (62.5 vs 25 mean scores respectively). Chemotherapy was associated with more diarrhoea complaints, lower "role", lower "social functioning" and lower global health quality of life scale., Conclusion: The overall quality of life of patients with rectal cancer is quite good 4.6 years after the beginning preoperative treatments. However, adding chemotherapy to preoperative radiotherapy has a negative effect on diarrhoea complaints and some quality of life dimensions., (Copyright © 2010 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.)

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., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Purpose: The Gastro-Intestinal Working Party of the EORTC Radiation Oncology Group (GIWP-ROG) developed guidelines for target volume definition in neoadjuvant radiation of adenocarcinomas of the gastroesophageal junction (GEJ) and the stomach., Methods and Materials: Guidelines about the definition of the clinical target volume (CTV) are based on a systematic literature review of the location and frequency of local recurrences and lymph node involvement in adenocarcinomas of the GEJ and the stomach. Therefore, MEDLINE was searched up to August 2008. Guidelines concerning prescription, planning and treatment delivery are based on a consensus between the members of the GIWP-ROG., Results: In order to support a curative resection of GEJ and gastric cancer, an individualized preoperative treatment volume based on tumour location has to include the primary tumour and the draining regional lymph nodes area. Therefore we recommend to use the 2nd English Edition of the Japanese Classification of Gastric Carcinoma of the Japanese Gastric Cancer Association which developed the concept of assigning tumours of the GEJ and the stomach to anatomically defined sub-sites corresponding respectively to a distinct lymphatic spread pattern., Conclusion: The GIWP-ROG defined guidelines for preoperative irradiation of adenocarcinomas of the GEJ and the stomach to reduce variability in the framework of future clinical trials.

Purpose: Chemoradiotherapy (CRT) is an alternative to surgery for resectable locally advanced esophageal carcinoma (RLA-EC). We investigated the heterogeneity of the treatment benefits across subgroups of patients, defined according to the radiation scheme., Patients and Methods: Between February 1993 and December 2000, 451 patients were enrolled. The following two schemes were allowed: protracted radiotherapy (P-RT), which scheduled 46 Gy over 4.5 weeks or split-course radiotherapy (SC-RT) with two 1-week courses of 15 Gy. Two courses of cisplatin and fluorouracil were delivered concomitantly. In case of exclusive CRT, a further course of 20 Gy over 2 weeks in the P-RT group and one 1-week course of 15 Gy in the SC-RT group were delivered with three courses of chemotherapy. SC-RT and P-RT were administered to 285 patients (64%) and 161 patients (36%), respectively., Results: For P-RT versus SC-RT, the response rate to induction CRT was 67% v 68%, respectively (P = .09), and 2-year local relapse-free survival rate was 76.7% v 56.8%, respectively (P = .002). Shorter tumor length and P-RT were associated with better local control in multivariate analysis (P = .002 for both). After a median follow-up time of 47.4 months, 2-year overall survival rate was 37.1% for P-RT compared with 30.5% for SC-RT (P = .25). Independent prognostic factors on survival were tumor diameter (P = .02), weight loss of 10% or less (P = .05), and response to induction CRT (P = .002)., Conclusion: Patients with RLA-EC treated with P-RT had better local control than patients treated with SC-RT. Response to induction CRT is a determinant prognostic factor on survival.

Background: Preoperative radiotherapy is recommended for selected patients with rectal cancer. We evaluated the addition of chemotherapy to preoperative radiotherapy and the use of postoperative chemotherapy in the treatment of rectal cancer., Methods: We randomly assigned patients with clinical stage T3 or T4 resectable rectal cancer to receive preoperative radiotherapy, preoperative chemoradiotherapy, preoperative radiotherapy and postoperative chemotherapy, or preoperative chemoradiotherapy and postoperative chemotherapy. Radiotherapy consisted of 45 Gy delivered over a period of 5 weeks. One course of chemotherapy consisted of 350 mg of fluorouracil per square meter of body-surface area per day and 20 mg of leucovorin per square meter per day, both given for 5 days. Two courses were combined with preoperative radiotherapy in the group receiving preoperative chemoradiotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy; four courses were planned postoperatively in the group receiving preoperative radiotherapy and postoperative chemotherapy and the group receiving preoperative chemoradiotherapy and postoperative chemotherapy. The primary end point was overall survival., Results: We enrolled 1011 patients in the trial. There was no significant difference in overall survival between the groups that received chemotherapy preoperatively (P=0.84) and those that received it postoperatively (P=0.12). The combined 5-year overall survival rate for all four groups was 65.2%. The 5-year cumulative incidence rates for local recurrences were 8.7%, 9.6%, and 7.6% in the groups that received chemotherapy preoperatively, postoperatively, or both, respectively, and 17.1% in the group that did not receive chemotherapy (P=0.002). The rate of adherence to preoperative chemotherapy was 82.0%, and to postoperative chemotherapy was 42.9%., Conclusions: In patients with rectal cancer who receive preoperative radiotherapy, adding fluorouracil-based chemotherapy preoperatively or postoperatively has no significant effect on survival. Chemotherapy, regardless of whether it is administered before or after surgery, confers a significant benefit with respect to local control. (ClinicalTrials.gov number, NCT00002523 [ClinicalTrials.gov].)., (Copyright 2006 Massachusetts Medical Society.)

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.

Background and Purpose: We retrospectively analysed our experience of contact therapy alone and/or combined with interstitial brachytherapy as exclusive treatment of low lying rectal tumours., Patients and Methods: From 1971 to 2001, 124 patients (103 adenocarcinomas, 21 villous tumours) were treated by contact therapy alone or combined with interstitial brachytherapy. All patients were staged according to the Dijon classification. The average size of the lesions was 2.4 cm (max 7 cm), clinical aspect was polypoïd in 75% of the cases, flat in 17%. Sixty four patients received contact therapy in three fractions and 44 patients received four fractions, for an average delivered dose of 95 Gy. Interstitial brachytherapy boost delivered 24 Gy on a reference isodose of 55 cGy/h in 10 patients., Results: The local control was 83% for T1 and 38% for T2 tumours (p=0.004). For mobile tumours, the local control rate is 76%, significantly higher than for tumours with impaired mobility (55%, P=0.03). Thirty-nine patients experienced a local failure (31%). For patients amenable to surgery, a Miles procedure was performed in 25 patients. Ultimate local control rate is 93% for T1, 69% for T2 (P<0.05), 15 patients failed despite treatment for local recurrence (15%). No significant differences were observed in a comparison of adenocarcinoma and villous tumours according to initial and ultimate local control. The mean disease free survival rate for the whole population is 66 months. The 5-year disease free survival for T1a and T1b is, respectively, 82 and 78%, 40 and 25% for T2a and T2b, respectively. The overall 5-year survival for the whole group is 62.4%. At the end of the treatment, 75% of the patients described a very good sphincter function. No deleterious effect on continence was reported during the follow-up., Conclusions: The control rate for T1 rectal cancer treated with contact therapy with or without brachytherapy is comparable to surgical series. The sphincter was preserved in 80% of the patients. Radiotherapy remains an efficient and cheap alternative to surgery, mainly for old and fragile patients, or refusing colostomy. The results of these approaches for tumors larger than 3 cm (T2) are not satisfactory. For patients not amenable to surgery, external beam radiation therapy and/or combined modality with chemoradiation should be discussed to increase the loco-regional control rate. A careful selection of patients based on rectal examination and trans-rectal ultrasound could select more accurately patients amenable to such an approach.

Preoperative radiotherapy is the standard treatment for locally advanced resectable rectal adenocarcinoma. The total mesorectal excision leads to a dramatic increase of local control rate. Thus, the mesorectal space is the usual field for the spread of rectal cancers cells. It could therefore be considered as the clinical target volume (CTV) in the preoperative conformational radiotherapy. From the anatomical basis and radiological contributions, we propose several CTVs for different locations of rectal carcinoma.

The delineation of target volume and organs at risk depends on the organs definition, and on the modalities for the CT-scan acquisition. Inter-observer variability in the delineation may be large, especially when patient's anatomy is unusual. During the two french multicentric studies of conformal radiotherapy for localized prostate cancer, it was made an effort to harmonize the delineation of the target volumes and organs at risk. Two cases were proposed for delineation during two workshops. In the first case, the mean prostate volume was 46.5 mL (extreme: 31.7-61.3), the mean prostate and seminal vesicles volume was 74.7 mL (extreme: 59.6-80.3), the rectal and bladder walls varied respectively in proportion from 1 to 1.45 and from 1 to 1.16; in the second case, the mean prostate volume was 53.1 mL (extreme: 40.8-73.1), the volume of prostate plus seminal vesicles was 65.1 mL (extreme: 53.2-89), the rectal wall varied proportionally from 1 to 1, 24 and the vesical wall varied from 1 to 1.67. For participating centers to the french studies of dose escalation, a quality control of contours was performed to decrease the inter-observer variability. The ways to reduce the discrepancies of volumes delineation, between different observers, are discussed. A better quality of the CT images, use of urethral opacification, and consensual definition of clinical target volumes and organs at risk may contribute to that improvement.

Dedicated studies to esophageal carcinomas are few. Surgical excision remains the treatment of choice for localised tumours. External beam radiation therapy could be used alone to obtain a quick palliation and to allow the recovery of normal eating. Currently, combined modality treatment demonstrated better results when compared to radiation alone. Efficiency of combined modality treatment of adenocarcinoma seems equivalent to epidermoid. Numerous phase II studies demonstrated the feasibility of combined radio-chemotherapy in a preoperative setting. However, phases III trials are criticised and actually no definitive conclusion can be drawn. Inclusion of patients with such a tumour should be encouraged.

Objective: To study the safety of conformal radiotherapy dose escalation up to 80 Gy for curative treatment of prostate cancer., Material and Methods: A multicentre trial sponsored by the PHRC include 164 patients under the age of 75 years with stage T1b-T3 N0 M0 prostatic adenocarcinoma, between 1995 and 1998. The prostate was treated at 5 dose levels: 18 patients at 66 Gy, 28 at 70 Gy, 49 at 74 Gy, 48 at 78 Gy, 21 at 80 Gy. The acute and delayed toxicity was graded according to a multidisciplinary glossary. Quality of life was evaluated before and one year after treatment using the EORTC QLQ-C30 questionnaire and additional questions., Results: 89% and 55% of mild or moderate gastrointestinal and urinary adverse effects were observed during treatment, respectively. At long-term follow-up, of the 162 evaluable patients, 12.3% presented grade 2 adverse effects and 2.5% presented grade 3 adverse effects (1 case of haematuria, 2 urethral strictures, 1 bladder neck lesion) with no significant difference between the various dose levels. Two successive quality of life questionnaires were available for 119 patients: tiredness, pain and dyspnoea increased in parallel, but non-significantly in the groups receiving conventional doses or high doses. The proportion of patients reporting sexual activity without endocrine therapy decreased from 48% before treatment to 35% one year later. The proportion of patients with no clinical or laboratory signs of progression was higher in the high-dose group., Conclusion: No significant difference was observed between conventional dose levels and high dose levels in terms of toxicity or quality of life. As the adverse effects were acceptable, a randomized trial comparing 70 Gy and 80 Gy has been initiated.

Purpose: To evaluate the feasibility of dose escalation in a multi-institutional study in prostate cancer patients., Methods and Materials: Between October 1995 and October 1998, 164 patients with localized adenocarcinoma of the prostate were treated with 3-dimensional conformal radiotherapy at one of five French institutions. The dose of radiation was escalated from 66 to 80 Gy (ICRU point). The maximum dose to the rectal wall was limited to 75 Gy., Results: Results were compared in two groups, one (group 1) receiving the standard dose (n = 46 patients; 66 to 70 Gy) and the other (group 2) receiving the escalated dose (n = 118 patients; 74 to 80 Gy). There was no difference in the characteristics of patients between the two groups. The mean follow-up time was 32 months in group 1 and 17.5 months in group 2. No statistical difference between the two groups was observed in the incidence of late gastrointestinal and urinary toxicities. The probability of achieving a posttreatment prostate-specific antigen nadir of

Purpose: We analyzed our experience with external radiotherapy, combined modality treatment, or HDR brachytherapy alone to limited esophageal cancers., Methods and Materials: From 1991 to 1996, 25 patients with limited superficial esophagus carcinomas were treated by high dose rate brachytherapy. The mean age was 63 years (43-86 years). Five patients showed superficial local recurrence after external radiotherapy. Eleven patients without invasion of the basal membrane were staged as Tis. Fourteen patients with tumors involving the submucosa without spreading to the muscle were staged as T1. Treatment consisted of HDR brachytherapy alone in 13 patients, external radiotherapy and brachytherapy in 8 cases, and concomitant chemo- and radiotherapy in 4 cases. External beam radiation was administered to a total dose of 50 Gy using 2 Gy daily fractions in 5 weeks. In cases of HDR brachytherapy alone (13 patients), 6 applications were performed once a week., Results: The mean follow-up is 31 months (range 24-96 months). Twelve patients received 2 applications and 13 patients received 6 applications. Twelve patients experienced a failure (48%), 11/12 located in the esophagus, all of them in the treated volume. One patient presented an isolated distant metastasis. In the patients treated for superficial recurrence, 4/5 were locally controlled (80%) by brachytherapy alone. After brachytherapy alone, 8/13 patients were controlled (61%). The mean disease-free survival is 14 months (1-36 months). Overall survival is 76% at 1 year, 37% at 2 years, and 14% at 3 years. Overall survival for Tis patients is 24% vs. 20% for T1 (p = 0.83). Overall survival for patients treated by HDR brachytherapy alone is 43%. One patient presented with a fistula with local failure after external radiotherapy and brachytherapy. Four stenosis were registered, two were diagnosed on barium swallowing without symptoms, and two required dilatations., Conclusion: High dose rate brachytherapy permits the treating of patients with superficial esophageal cancer with good tolerance. Early tumors, located in the mucosa, might be treated by HDR brachytherapy alone or by a combined modality treatment in which HDR brachytherapy can take place like a boost. This approach may cure localized recurrences.

Purpose: The aim of this study was to analyze the experience of Centre GF Leclerc for conservative and curative treatment by radiotherapy of low rectal cancer., Patients and Methods: A total of 151 patients received radiotherapy alone for rectal adenocarcinoma with curative intent. They were clinically staged according to size (T1 < 3 cm, and T2 > 3 cm) and depth of infiltration (A=superficial, and B=impaired mobility and T3 fixed). Over the past 6 years, rectal ultrasound (US) has been used systematically, compared with computed tomographic scan and magnetic resonance imaging when needed. Intracavitary contact X ray was given to 129 patients (69%), and brachytherapy in 45 of 151. External radiotherapy was used in 34 cases (22.5%)., Results: Complete response was obtained in 93%. Local failures were observed in 50 cases (28%); two occurred in pelvic nodes after intracavitary X rays. Size (tumors > 3 cm) and alteration of mobility significantly influenced the rate of local failure (p=0.009 and 0.007). The addition of external radiotherapy in patients with poor prognostic factors improved the local control rate. A total of 39 patients with recurrence were amenable to salvage surgery. After salvage treatment, the local control rate was 82% with unlimited follow-up. The 5-year actuarial survival rate was 57%, with a specific survival of 66%. There was no difference in local control or survival according to differentiation of the tumors and distance between anal margin and the inferior level of the lesion. Severe late effect (grade 3) was 3.8%. The sphincter preservation was obtained in 104 of 124 cases (84%). The sphincter function was judged to normal in 102 of 104 patients (98%)., Conclusion: Intracavitary contact X ray is the treatment of choice for clinical Stage T1A rectal tumors. External radiotherapy significantly improved the results of treatment of tumors > 3 cm. Clinical staging and transrectal ultrasound allows a safe selection of indications. Radiotherapy alone may be proposed for selected cases as an alternative to mutilating surgery for small rectal adenocarcinoma.

From 1972 to 1993, 170 patients received preoperative radiotherapy followed, 5-6 weeks later, by total extrafascial hysterectomy with bilateral salpingo-oophorectomy without lymphadenectomy. Eighty-three patients with good prognostic factors (low grade tumour and no cervical involvement) received low dose rate utero vaginal brachytherapy alone before surgery (Group 1). Eighty-seven patients with poor prognostic factors (high grade tumors and/or cervical involvement) received external radiotherapy to 40 Gy and low dose rate brachytherapy before surgery (Group 2). A single vaginal failure was observed (0.6%). The overall pelvic failure rate was 2.3% (four patients) including two cases with pelvic recurrence and metastases. Three of the four pelvic failures occurred in Group 1. Using the 1971 FIGO clinical staging, 5-year disease-free survival was 82% in Stage Ia, 79% in Stage Ib, and 81% in Stage II (P = 0.36). Five-year disease-free survival was 86% in Grade 1, 76% in Grade 2, and 83% in Grade 3 (P = 0.20). Five-year overall survival was 83% in Stage Ia, 79% in Stage Ib, and 83% in Stage II (P = 0.78). Five-year overall survival was 88% in Grade 1, 77% in Grade 2,83% in Grade 3 (P = 0.27). Complications were recorded with the French-Italian syllabus. Grade 2 complications occurred in 12 cases (7%), Grade 3 in five cases (3%). The lack of correlation between classical risk factors (stage, grade) and disease outcome suggests that preoperative radiotherapy strategies should be preferred when such factors can be identified before surgery.

Two hundred patients with well-differentiated adenocarcinomas of the rectum stages T1, T2 (113 T1, 87 T2) were accrued in two French institutions (Lyon-Sud and Dijon). Treatment consisted of intracavitary 50 kV X-rays (90-120 Gy in 3-4 fractions and 4-6 weeks). A 20-30 Gy interstitial brachytherapy boost was given after 2-3 fractions when a limited infiltration of the rectal wall was present. Local failure occurred in 4.4% of T1, 19.5% of T2; nodal failure in 0.9% of T1, 9.2% of T2. Ultimate local control after salvage of failures is 94.5%. A functional sphincter was preserved in 95% of patients with local control.

Abstract: Esophageal cancer is characterized by various degrees of lymph node invasion and metastasis, both of which are associated with a poor prognosis. Exclusive concomitant radiochemotherapy (RCT) at a dose of 50 Gy delivered over 25 sessions, according to the RTOG 85-01 protocol, has led to improved five-year survival in 25% of patients, whereas no patients survive for five years using radiotherapy alone. Surgery, even when combined with preoperative RCT, also gives disappointing results for locally advanced tumors, which casts serious doubts on the usefulness of preoperative radiotherapy. By varying the fractionation schedule, the length of treatment or the radiotherapy volumes, it has become possible to obtain levels of locoregional relapse of around 35 to 45%. The increasing incidence of adenocarcinoma, which differs from epidermoid cancer with regard to the degree of lymph node invasion, has revived discussion on radiotherapy volumes. Given this difference between these two histological forms, we propose here a number of recommendations concerning radiotherapy volumes for patients presenting with cancer of the esophagus. Finally, analysis of the results for locoregional relapse according to the dose of radiation and the recommended radiotherapy volumes, has led us to investigate why increasing the dose of radiation has no impact in esophageal cancers. [Copyright &y& Elsevier]

Abstract: Adenocarcinoma of the oesophagogastric junction has an ominous prognosis. Until now, oesophageal adenocarcima care was close to the squamous cell cancer one whereas adenocarcinoma of the cardia was mixed with gastric cancers. Results from randomised studies mixed them without making distinctions. Nevertheless, context, natural history and clinical outcome differ. Five-year survival rate is around 40 %, all stages included. Results from several phase-III studies or meta-analysis allowed to define three therapeutic strategies applicable to adenocarcinoma of the oesophagus and the oesophagogastric junction. In Europe, in the case of a resectable tumour, preoperative chemotherapy became a standard treatment since results from the Magic trial. In the United States, post-operative radiochemotherapy according to the “Macdonald” scheme is used in case of a resected tumour with a R0 surgery. Actually, modern techniques of irradiation could reduce the rate of gastro-intestinal toxicities. The survival benefit from preoperative radiochemotherapy is still very controversial with high rates of postoperative morbidity and mortality. We have performed a review of the litterature with a methodological analysis of data with a high level of evidence in order to advise perioperative treatment guidelines for patients with a resectable adenocarcinoma of the lower oesophagus or gastro-oesophageal junction. Results from pre- or postoperative strategies and the role of radiotherapy will need to be analysed in the future through a randomised study. [Copyright &y& Elsevier]