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Radiation-induced nausea and vomiting (RINV) affect the management and quality of life of cancer patients. Current guidelines for RINV prevention recommend prophylaxis with a 5-hydroxytryptamine (5-HT3)-receptor antagonist for patients receiving moderately or highly emetogenic radiotherapy regimens. Randomised trials have compared such antagonists with conventional antiemetics, and have demonstrated their efficacy and safety. Special consideration is needed for antiemetic treatment in certain patient groups, particularly the elderly and those with renal or hepatic impairment. Radiation oncologists should be aware of the effect on antiemetic treatment of factors such as comorbid conditions (particularly cardiovascular disease), polypharmacy and drug–drug interactions, and choose the agent with the lowest potential for additional complications. The most appropriate antiemetic treatment to improve patient compliance and quality of life should ideally combine proven efficacy with uncomplicated administration and convenient dosing regimens.

De 1985 a 1991, 52 malades ont ete traites au Centre Georges Francois-Leclerc pour des metastases osseuses des os longs. L'association chirurgie et irradiation permet d'obtenir un controle clinique de la douleur chez 75 % des patients, quel que soit le type d'intervention et le choix technique chirurgical ou de radiotherapie. La fonction du membre est conservee dans 83 % des cas, quel que soit le site osseux ou le materiel utilise. Chez 31 malades qui ont beneficie d'une sequence therapeutique comportant un enclouage fascicule suivi d'une radiotherapie externe complementaire, les resultats sont identiques et une prevention satisfaisante du risque fracturaire (4/33 interventions) est assuree. L'analyse des parametres para-cliniques de l'evolution permet de constater 1 reponse complete, 4 reponses partielles, 10 stabilisations radiologiques et 4 progressions de l'osteolyse qui ne sont jamais associees a la survenue d'une fracture secondaire.

A randomised controlled clinical trial of Ro 03-8799 (pimonidazole) was performed in advanced stage II and stage III squamous cell carcinoma of the uterine cervix. A total of 183 patients were contributed by 15 centres in Western Europe and coordinated by the Medical Research Council Trials Office in Cambridge. Analysis has shown poorer local tumour control with a hazard ratio (HR) of 2.1 [95% confidence interval (CI) 1.2 to 3.7] and survival with a HR of 1.6 (95% CI 1.0 to 2.5) in the group given the Ro 03-8799. These results were not materially affected after adjustment of stage or haemoglobin levels in stratified analysis or to inadequate radiotherapy being given to the sensitiser group. A true adverse effect caused by the drug is a possible cause and this might be related to a drug-induced impairment of blood supply to the tumour. When compared with results recorded previously for advanced cervical carcinoma treated by radiotherapy, it was apparent that the tumour control and survival in the sensitiser arm was similar, but the control arm showed results superior to those previously recorded. Whatever is the explanation it can certainly be concluded that the radiosensitising drug, pimonidazole, gave no benefit in the radiotherapy of advanced cervical cancer.

Background: Both induction chemotherapy followed by irradiation and concurrent chemotherapy and radiotherapy have been reported as valuable alternatives to total laryngectomy in patients with advanced larynx or hypopharynx cancer. We report results of the randomized phase 3 trial 24954 from the European Organization for Research and Treatment of Cancer. Methods: Patients with resectable advanced squamous cell carcinoma of the larynx (tumor stage T3T4) or hypopharynx (T2T4), with regional lymph nodes in the neck staged as N0N2 and with no metastasis, were randomly assigned to treatment in the sequential (or control) or the alternating (or experimental) arm. In the sequential arm, patients with a 50% or more reduction in primary tumor size after two cycles of cisplatin and 5-fluorouracil received another two cycles, followed by radiotherapy (70 Gy total). In the alternating arm, a total of four cycles of cisplatin and 5-fluorouracil (in weeks 1, 4, 7, and 10) were alternated with radiotherapy with 20 Gy during the three 2-week intervals between chemotherapy cycles (60 Gy total). All nonresponders underwent salvage surgery and postoperative radiotherapy. The KaplanMeier method was used to obtain time-to-event data. Results: The 450 patients were randomly assigned to treatment (224 to the sequential arm and 226 to the alternating arm). Median follow-up was 6.5 years. Survival with a functional larynx was similar in sequential and alternating arms (hazard ratio of death and/or event = 0.85, 95% confidence interval = 0.68 to 1.06), as were median overall survival (4.4 and 5.1 years, respectively) and median progression-free interval (3.0 and 3.1 years, respectively). Grade 3 or 4 mucositis occurred in 64 (32%) of the 200 patients in the sequential arm who received radiotherapy and in 47 (21%) of the 220 patients in the alternating arm. Late severe edema and/or fibrosis was observed in 32 (16%) patients in the sequential arm and in 25 (11%) in the alternating arm. Conclusions: Larynx preservation, progression-free interval, and overall survival were similar in both arms, as were acute and late toxic effects.

Colorectal cancer (CRC) is one of the commonest malignancies of Western countries, with approximately half the incidence occurring in patients >70 years of age. Elderly CRC patients, however, are understaged, undertreated and underrepresented in clinical trials. The International Society of Geriatric Oncology created a task force with a view to assessing the potential for developing guidelines for the treatment of elderly (geriatric) CRC patients. A review of the evidence presented by the task force members confirmed the paucity of clinical trial data in elderly people and the lack of evidence-based guidelines. However, recommendations have been proposed on the basis of the available data and on the emerging evidence that treatment outcomes for fit, elderly CRC patients can be similar to those of younger patients. It is hoped that these will pave the way for formal treatment guidelines based upon solid scientific evidence in the future.

As early as in 1982, the European Organisation for Research and Treatment of Cancer Radiotherapy Group established a quality assurance programme. In the course of 20 years, quality assurance procedures have become a vast and important part of the activities of the group. Today, the membership committee uses standard procedures based on minimal requirements to evaluate current members and new membership applications. Moreover, for every new trial, specific quality assurance procedures are an integral part of the preparation of the protocol and executed under the responsibility of the study coordinator. With the growing complexity of the radiotherapy techniques used in the framework of the more recent trials, quality assurance procedures have also become more complex including trial specific phantom based measurements. Future ways to evaluate all steps of the radiotherapy process using a common platform connecting all users with the internet are currently under development.

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.

In 1982, the European Organization for Research and Treatment of Cancer (EORTC) Radiotherapy Group established the Quality Assurance (QA) programme. During the past 20 years, QA procedures have become a major part of the activities of the group. The methodology and steps of the QA programme over the past 20 years are briefly described. Problems and conclusions arising from the results of the long-lasting QA programme in the EORTC radiotherapy group are discussed and emphasised. The EORTC radiotherapy group continues to lead QA in the European radiotherapy community. Future challenges and perspectives are proposed.

A randomised phase II trial was initiated to explore the feasibility of concomitant cisplatin and radiotherapy with conventional fractionation (CF) or multiple fractions per day (MFD) for patients with locally advanced head and neck malignancies. The MFD schedule was designed to achieve higher tumour concentrations of cisplatin at the time of irradiation by reducing the number of radiation treatment weeks from 7 to 3, allowing recovery from side-effects of both irradiation and cystostatic drugs during the rest periods, while keeping the same total dose and overall treatment time. Patients were randomised between a conventional fractionation scheme (CF) of 70 Gy in 7 weeks with 2 Gy per fraction with a daily dose of 6 mg/m(2) cisplatin and a modified fractionation scheme (MFD) delivering three fractions of 1.6 Gy per day, in weeks 1, 4 and 7, keeping the same overall treatment time and total dose. In the modified treatment regime, a daily dose of 10 mg/m(2) cisplatin was administered. 53 patients were entered in this trial and radiotherapy was given according to the schedule to all patients in both treatment arms. Cisplatin was given during the whole course of radiotherapy to only one quarter of the patients in the CF arm, stopping mostly after 5-6 weeks due to bone marrow depression and kidney toxicity, while patients in the MFD arm received it according to schedule. No difference was observed in acute and late toxicity in both treatment arms, while a similar or even better tumour response was obtained with MFD. A 67% higher daily dose of cisplatin concomitant with irradiation could be given in a 3-week multiple fractionation per day schedule, as opposed to the cisplatin given in the conventional daily fractionation schedule of 7 weeks with the same total radiation dose. Similar acute and late toxicities were seen in both treatment arms.

The European Organisation for Research and Treatment of Cancer (EORTC) Radiotherapy (RT) Group will celebrate 27 years of activity in 2002. During its long history, the Radiotherapy Group has conducted a large number of studies which have provided valuable information on the radiation treatment of several disease sites. Group efforts have been concentrated on dose-effect studies, optimal fractionation schemes, combinations with other treatment modalities, and new radiotherapy techniques. The EORTC RT Group was the first in Europe to develop and introduce methodologies of Quality Assurance in radiotherapy. The RT Group actively collaborates with other EORTC Groups and international organisations. Currently, several phase III studies are being conducted in collaboration with European, North American and Australian organisations. The collaboration with RTOG led to the setting up of common systems for scoring late normal tissue effects. In the years to come, the Group will keep pioneering pivotal trials in radiotherapy and radio-chemotherapy. It will also explore combinations with novel therapies in phase I trials and implement innovative translational research programmes.

To study the safety of conformal radiotherapy dose escalation up to 80 Gy for curative treatment of prostate cancer.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.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.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.

Preoperative radiotherapy (RT) alone or in combination with a pre- or postoperative chemotherapy reduces the recurrence rate and increases the survival rate for patients with resectable rectal cancer. The therapeutic index, i.e. relationship between effects and side effects is objective of studies. Especially toxicities to the small intestine and to the sphincter function are evaluated. Preoperative radiotherapy achieves the best results. The treatment volume includes the mesorectum in case of continence maintaining surgery and includes the anal sphincter in case of abdominoperineal resection. To exclude the small intestine from the RT-field, we prefer the use of 3 or 4 field technique in a prone position with filled bladder, using an optimal field limitation. The Swedish study, which uses 25 Gy in five fractions per week leads to an increased rate of acute and late toxicities. A fractionation schedule using 45-50 Gy in five weeks should be preferred. During the radiotherapy the patient is followed-up once per week. If surgery is foreseen, it should take place as soon as 3 weeks after the end of radiotherapy. If a primary surgery is performed preoperatively, the operative finding should be discussed with the surgeon. Quality control programs have to certify optimal treatment of the patient by radiotherapist and surgeon.

Improvement in the accuracy of the positioning of the patient during external irradiation is one of the most important issues of the last decades, due to the detrimental impact of the misplacements on treatment outcome. Since 1990, the evolution of the technologic environment has led to a full integration of the portal imaging devices into linac technology. It offers a real on-line verification tool for "high-dose, high-accuracy" treatments. This overview based upon data from the literature describes the different types of imaging devices, the strategies of use and the results obtained. It also considers the use of imaging devices as an in vivo dosimeter.

The prospective record of acute and late toxicity after treatment of cervix carcinomas is a part of the description of treatment outcome as well as local control and survival. Due to the large number of scales and glossaries used, the comparison of the results from one study to another is often difficult. The French-Italian syllabus seems to be the most reliable scale, providing implementation of quality of life assessments. The main predictive factor of complications, which is not related to the treatment type, is the previous history of abdominal or pelvic surgery. The incidence and severity of complications occurring after surgery are related to the surgical procedure and to the amount of peri-uterine tissues removed. The increase in dose and volume of external irradiation and brachytherapy and the increase in dose rate of the low-dose rate brachytherapy are responsible for the radiotherapeutic morbidity. The significant decrease of severe complication rates during the last 15 years was obtained by the implementation of individual adjustments in treatment planning. The treatment strategies of early bulky and advanced carcinomas are changing. Concurrent radiotherapy and chemotherapy is becoming a standard, but its late toxicity needs to be documented by a longer follow-up. The optimisation of radiation therapy should remain a reference to evaluate the outcome and morbidity of the new combined strategies: the addition of chemotherapy will never compensate for less than optimal radiotherapy/brachytherapy planning.

To describe the evolution of the use of the electronic portal imaging device (EPID) over three periods.From 1990, as part of the quality assurance research programs, the radiotherapy department of the G.-F. Leclerc Centre of Dijon used EPID systems in a prospective fashion. During the first of the three periods (PER 1:1990-1993), the study consisted of analysis criteria determination, software efficiency improvement and a selection of patients who could benefit from the method. Eight hundred and forty-five images of 40 patients were analysed qualitatively and quantitatively. Two verifications per week were planned, and the action level for correction was 10 mm. Head and neck images were also displayed in 'cinema' presentation for internal movements analysis. From 1994 to 1995 (PER 2), off-line procedure (OLP) based upon early correction of the systematic error and the rules calculated from our previous experience were tested for checking the brain, head and neck (LOC 1: 396 images) and many of the pelvic irradiations (LOC 2: 260 images). A double-exposure procedure and/or movie loop presentation was reserved for other patients. During the last period (PER 3: 1996-1997), the OLP procedure was routinely performed in 54 patients (images: 321 LOC 1, 680 LOC 2).LOC 1: deviations of3 mm increased from 75.5% during PER 1 to 81% during PER 2 to 83% during PER3. Conversely, deviations of 3-5 mm dropped from 19.5 to 13%, while deviations of more than 5 mm remained stable, around 5%. The actual standard error of the mean deviation observed was 2 mm. LOC 2: deviations of5 mm were observed in 81% of the cases during PER 1 and in 91% during PER 3 (89.5% in PER 2). These good results led to a decrease in deviation of 5 to 7 mm (11 to 6%) and also to a significant drop in deviations of more than 7 mm, 8 to 3% respectively. The actual precision obtained was 2.5 mm +/- 3 mm SD.The OLP based upon the early correction of the systematic error led to a significant increase of setup accuracy of patients irradiated for the brain, head and neck, and especially for pelvic lesions.

To assess toxicity and long-term results of preoperative chemoradiotherapy in rectal cancer.Between 1989 and 1997, as a phase II study, 66 patients with T3 M0, rectal cancer received preoperatively a 45 Gy dose pelvic radiotherapy (XRT) combined with two 5-day chemotherapy courses (CT) of 5-Fluorouracil (5-FU) and Leucovorin (LV) delivered the first and fifth week of XRT. For each CT course, LV:20 mg/m2/d1-d5,. While the 5-FU dose was variable from 450 to 350 mg/m2/d first course and 370 to 350 mg/m2/d second course. Surgery was planned 3 weeks later.XRT-CT was stopped in 1 patient due to progressive disease. CT was stopped in 1 patient due to toxicity. Grades 2 and 3 diarrhea were observed in 8 and 3 patients, respectively. One patient died from acute diarrhea due to deviation from recommendations; 60 patients went to surgery. Among the 58 patients operated on for cure, 5 had an R1-resection. After a 4.5-year median follow-up, the 5-year pelvic disease-free survival was 92% for the whole group and 96% in the R0-resection group.Preoperative combined XRT-5-FU-LV is feasible if optimal XRT and patients are carefully managed. The recommended 5-FU daily dose is 350 mg/m2 for both CT courses. This approach is currently tested in a large EORTC phase III trial.

To evaluate both qualitative and quantitative scoring methods for the cosmetic result after breast-conserving therapy (BCT), and to compare the usefulness and reliability of these methods.In EORTC trial 22881/10882, stage I and II breast cancer patients were treated with tumorectomy and axillary dissection. A total of 5318 patients were randomized between no boost and a boost of 16 Gy following whole-breast irradiation of 50 Gy. The cosmetic result was assessed for 731 patients in two ways. A panel scored the qualitative appearance of the breast using photographs taken after surgery and 3 years later. Digitizer measurements of the displacement of the nipple were also made using these photographs in order to calculate the breast retraction assessment (BRA). The cosmetic results after 3-year follow-up were used to analyze the correlation between the panel evaluation and digitizer measurements.For the panel evaluation the intraobserver agreement for the global cosmetic score as measured by the simple Kappa statistic was 0.42, considered moderate agreement. The multiple Kappa statistic for interobserver agreement for the global cosmetic score was 0.28, considered fair agreement. The specific cosmetic items scored by the panel were all significantly related to the global cosmetic score; breast size and shape influenced the global score most. For the digitizer measurements, the standard deviation from the average value of 30.0 mm was 2.3 mm (7.7%) for the intraobserver variability and 2.6 mm (8.7%) for the interobserver variability. The two methods were significantly, though moderately, correlated; some items scored by the panel were only correlated to the digitizer measurements if the tumor was not located in the inferior quadrant of the breast.The intra- and interobserver variability of the digitizer evaluation of cosmesis was smaller than that of the panel evaluation. However, there are some treatment sequelae, such as disturbing scars and skin changes, that can not be evaluated by BRA measurements. Therefore, the methods of cosmetic evaluation used in a study must be chosen in a way that balances reliability and comprehensiveness.

To evaluate the influence of a radiotherapy boost on the cosmetic outcome after 3 years of follow-up in patients treated with breast-conserving therapy (BCT).In EORTC trial 22881/10882, 5569 Stage I and II breast cancer patients were treated with tumorectomy and axillary dissection, followed by tangential irradiation of the breast to a dose of 50 Gy in 5 weeks, at 2 Gy per fraction. Patients having a microscopically complete tumor excision were randomized between no boost and a boost of 16 Gy. The cosmetic outcome was evaluated by a panel, scoring photographs of 731 patients taken soon after surgery and 3 years later, and by digitizer measurements, measuring the displacement of the nipple of 3000 patients postoperatively and of 1141 patients 3 years later.There was no difference in the cosmetic outcome between the two treatment arms after surgery, before the start of radiotherapy. At 3-year follow-up, both the panel evaluation and the digitizer measurements showed that the boost had a significant adverse effect on the cosmetic result. The panel evaluation at 3 years showed that 86% of patients in the no-boost group had an excellent or good global result, compared to 71% of patients in the boost group (p = 0.0001). The digitizer measurements at 3 years showed a relative breast retraction assessment (pBRA) of 7.6 pBRA in the no-boost group, compared to 8.3 pBRA in the boost group, indicating a worse cosmetic result in the boost group at follow-up (p = 0.04).These results showed that a boost dose of 16 Gy had a negative, but limited, impact on the cosmetic outcome after 3 years.

From 1978 to March 1998, (1,867 patients) were accrued in head and neck trials comparing hyperfractionation (HF) and accelerated fractionation (AF) to classical fractionation (CF). Two randomized trials (867 pts) led to positive conclusions in favour of the HFAF arms: 1) EORTC trial 22791 (356 patients, 1980-87) compared CF (70 Gy/35-40 fr/7-8 wks) to HF (80.5 Gy/70 fr/7 wks, using 2 fr x 1.15 Gy/day) in T2 T3, N0-N13 cm in oropharyngeal carcinoma. Locoregional control (LRC) was higher (p = 0.01) in HF versus CF. At 5 years, 56% of the patients are LRC free with HF versus 38% with CF on the latest update (February 1998). This improvement of LRC also resulted in a significant overall survival (p = 0.05). There was no difference in late normal tissue damage between the two treatment modalities. Overall, this is the largest improvement documented in a randomised trial for oropharyngeal cancers during the past decade. 2) EORTC trial 22851 (511 patients, 1985-1995) compared AF (72 Gy/45 fr/5 wks) to CF (70 Gy/35 fr/7 wks) in T2 T3 T4 headneck cancers (hypopharynx excluded). Acute and late toxicity were increased in the AF arm. Late severe sequelae occurred in 14% of patients of the AF arm versus 4% in the CF arm. Two cases of radiation-induced myelitis occurred after doses of 42 and 48 Gy to the spinal cord. The AF arm is significantly better for locoregional control (p = 0.017) and for time to progression (p = 0.012) resulting in a 15% locoregional gain at 5 years over the CF arm. This improvement is of larger magnitude in patients with poorer prognosis (N3 any T, T4 any N) than in patients with more favourable stage. Multivariate analysis confirmed AF as an independent pronostic factor for local control (p = 0.03). Specific survival shows a non significant advantage (p = 0.06) in favour of the AF arm. This trial shows that accelerated radiotherapy is able to improve locoregional control in a large variety of head and neck squamous cell carcinomas. A less toxic scheme should however be investigated before moving AF schemes in standard practice. To conclude, these two schemes derived from experimental radiobiology concepts resulted in a significant improvement of locoregional control. Hyperfractionation resulted in an improved locoregional and survival benefit. Although HF is presently the most reliable regimen to improve locoregional control, the validity of the concept of AF is also confirmed. Better schemes of AF should now be evaluated to reduce late toxicity.

From 1970 to 1994, 642 patients with carcinomas of intact uterine cervix were treated with radiotherapy alone Univariate and multivariate analysis was carried out of predictive factors for: 1) pelvic control and survival rates; 2) complications using French-Italian Syllabus, combined with an evaluation of the impact of customized treatment planning policy (CTP) on G3-G4. According to Figo substaging 30% of patients were stage I, 42% stage II and 28% stage III/IV. Diameter of cervical disease was 3-5 cm in 38% of cases and5 cm in 15%. Nodal involvement from lymphangiogram was 21%. The distribution of sequelae and complications was: G1 23%, G2 18%, G3 6%, G4 2.5%. The distribution of G3-G4 per organ was: genitalia 6% (no G4), rectum 4%, colon 1.5%, bladder 1.2%, soft tissues 1%, small bowel 0.5%. Stage (RR ranging from 1.5 for stage IIb to 5 for stage III/IV), tumor size (RR = 1.5), nodal involvement (RR = 2) were significant predictive factors for survival and pelvic control rates (p0.0001). In univariate analysis the main factors influencing the risk of G3-G4 complications were: Figo substaging, external radiation dose over 40 Gy (ED), parametrium boost (PB), use of brachytherapy vaginal cylinders applicator (CA), high HWT and mean rectal dose rate for rectal complications. In multivariate analysis, CA remained the only predictive factor for G3-G4 bladder events (odds ratio OR = 10.8) while the increase of mean dose rate (OR = 1.1), use of CA (OR = 4.2) and ED40 Gy (OR = 4.4) were predictive of severe rectal sequelae. Prevention of complications based upon individual changes of treatment planning according to dosimetry parameters led to a sharp decrease in severe complications with time. No G4 occurred after 1983. G3 rates dropped from 5% before 1978 to 0% after 1983 in stage I, from 10% to 6% in stage II and from 23% to 12% in stages III/IV. Meanwhile 5-year LC rates remained stable in early stages, about 91% in stage I and 85% in stage II, conversely they fell from 75% to 55% in stages III/IV, thus raising the problem of underdosage and/or more reliable staging with time. It is concluded that radiotherapy prescriptions based upon tumor diameter per stage and delivered using CTP led to an eradication of lethal complications and provided significant decrease of G3 in all cases while maintaining high cure rates in early stages. Dose reduction should be considered with caution in stages III/IV.

In December 1994, The French Consensus Conference on the Treatment of Rectal Cancer stated that: "Preoperative irradiation improves local control in T3 and T4 resectable rectal cancer patients and is recommended". Recent data indicate that this approach not only reduces local failure but also increases overall survival. The therapeutic ratio depends on the total dose delivered and technical parameters. Inadequate radiotherapy techniques leeds to increased toxicity and masks the potential benefits of the treatment. Combined preoperative chemo-radiotherapy, a promising issue in rectal cancer patients, is now under evaluation in a large European phase III trial (EORTC 22921).