Treatment of the elderly colorectal cancer patient: SIOG expert recommendations.

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.

The addition of a boost dose on the primary tumour bed after lumpectomy in breast conserving treatment for breast cancer. A summary of the results of EORTC 22881-10882 "boost versus no boost" trial.

PURPOSE: To investigate the impact of the boost dose to the primary tumour bed in the framework of breast conserving therapy on local control, cosmetic results, fibrosis and overall survival for patients with early stage breast cancer. PATIENTS AND METHODS: Five thousand five hundred and sixty-nine patients after lumpectomy followed by whole breast irradiation of 50 Gy were randomised. After a microscopically complete lumpectomy (5318 patients), the boost doses were either 0 or 16 Gy, while after a microscopically incomplete (251 patients) lumpectomy randomisation was between 10 and 26 Gy. The results at a median follow-up of 10 years are presented. RESULTS: At 10 years, the cumulative incidence of local recurrence was 10.2% versus 6.2% for the 0 Gy and the 16 Gy boost groups (p < 0.0001) and 17.5% versus 10.8% for the 10 and 26 Gy boost groups, respectively (p > 0.1). There was no statistically significant interaction per age group but recurrences tended to occur earlier in younger patients. As younger patients had a higher cumulative risk of local relapse by year 10, the magnitude of the absolute 10-year risk reduction achieved with the boost decreased with increasing age. Development of fibrosis was significantly dependent on the boost dose with a 10-year rate for severe fibrosis of 1.6% after 0 Gy, 3.3% after 10 Gy, 4.4% after 16 Gy and 14.4% after 26 Gy, respectively. CONCLUSION: An increase of the dose with 16 Gy improved local control for patients after a complete lumpectomy only. The development of fibrosis was clearly dose dependent. With 10 years median follow-up, no impact of survival was observed.

The quality assurance programme of the Radiotherapy Group of the European Organisation for Research and Treatment of Cancer: past, present and 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.

Effects of combined irradiation and doxorubicin treatment on cardiac function and antioxidant defenses in the rat.

Combined radiotherapy and chemotherapy have represented a major advance in the therapeutic management of cancer therapy. However, the combination of doxorubicin (DXR) and cardiac irradiation (IRR) could precipitate the unexpected expression of congestive heart failure. Oxidative lesions induced by IRR and DXR could represent one of the pathogenic factors of myocardial dysfunction. Our investigations were performed to evaluate in the rat: 1) cardiac functional changes, 2) cardiac and plasma peroxidative damage and antioxidant defenses variations, that occur 24 h (acute effects) and 30 d (middle term effects) following DXR treatment 1 mg/kg(-1)/day(-1) IP for 10 d and a 1 x 20 Gy cardiac gamma-irradiation. Our results showed that DXR affected heart reactivity as early as the end of its administration, although irradiation exerted no detectable effect. Antioxidant defenses disturbances in hearts of DXR treated rats were characterized by vitamins C and E decreases, catalase activity induction and an increase in lipid peroxidation. Moreover, plasma vitamin C consumption and the lower level of plasma lipid peroxidation attested to the efficient solicitation of antioxidant defenses that probably contributed to the preservation of cardiac function at 24 h. After 30 d, cardiac dysfunction became symptomatic at rest, resulting from DXR cardiac toxicity. In spite of the persistent activation of cardiac catalase activity, antioxidant deficiency and increased plasma and cardiac lipid peroxidation highlighted defenses overtaken. Thus, different physiopathological mechanisms are involved in heart disturbance at acute and middle terms, IRR and DXR acting on distinct targets without disclosing synergistic effects. After 30 d, cardiac and plasma biochemical abnormalities were emphasized by the combined DXR+IRR therapy, pointing out the severity of the damage. Oxidative damage to the heart induced both by irradiation and DXR, may be one of the pathogenic factors of myocardial dysfunction. There is the possibility that the deleterious effects might be limited by the use of pharmacologic antioxidant agents.

Treatment implications for radiation-induced nausea and vomiting in specific patient groups.

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-HT(3))-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.

Adjuvant treatment in the curative management of rectal cancer: a critical review of the results of clinical randomised trials.

A critical analysis of the results of randomised studies on adjuvant rectal cancer led to a different interpretation than given by the 1990 National Institutes of Health (NIH) conference which concluded that combined postoperative chemotherapy and radiotherapy resulted in increased local control and survival in stage II and III patients. We think there is not as yet indisputable evidence for the use of such combination postoperatively. Furthermore, this approach resulted in increased toxicity and was only consistent with moderate compliance. Conversely, preoperative radiotherapy, which was not even mentioned in the conclusions and recommendations of the NIH consensus conference, definitely increases local control and should now be proposed as standard initial treatment in T3T4 resectable rectal cancer. Moreover, preoperative concomitant chemotherapy is an attractive area for clinical trials.

Conservative and curative management of rectal adenocarcinomas by local radiotherapy alone.

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.

EORTC Radiotherapy Group: achievements and future projects. European Organisation for Research and Treatment of Cancer.

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.

Quality assurance in radiotherapy: from radiation physics to patient- and trial-oriented control procedures.

The stepwise process of the EORTC Quality Assurance Programme in Radiotherapy is described in function of two main criteria: the targets of the quality control procedures implemented, in Radiation Physics and clinical research, by the EORTC Radiotherapy Group and the development of both trial- and patient-oriented quality systems. This exhaustive program, which started in 1982, is characterised by three main periods. The first one was fully dedicated to pioneer steps in Radiation Physics measurements, on-site audits and inventories of human resources, staff workload and department infrastructure in institutions participating to EORTC trials. During the second period, which started in the late 1980s, a series of quality systems were implemented to test the compliance of the investigators to follow protocol guidelines, through the use of standard and uniform control procedures like the dummy runs, in order to tackle systematic errors in the participating institutions. Finally, the third period, which took place in the 1990s, was essentially patient-oriented, thanks to large scale individual case reviews, to check the validity of data recording and reporting processes and trace random errors throughout the radiotherapy treatments. Most of the results collected during these two decades allowed the implementation of well codified quality control procedures which, nowadays, can be used outside the field of clinical research, by national societies or bodies willing to improve treatment standards on a large scale.

No age limit for radical radiotherapy in head and neck tumours.

The elderly are often treated less aggressively in an attempt to preserve their quality of life with regards to toxicity. However, there are few data regarding the acute and late toxicity of radiotherapy (RT) in elderly patients. From February 1980 to March 1995, 1589 patients with head and neck cancers who enrolled in EORTC trials received RT and were available for analysis on RT toxicity. Patients over 65 years of age were in excess of 20%. Data regarding age and acute objective mucosal reactions were available for 1307 patients and 1288 had toxicity > or = grade 1. Age and acute functional mucosal reactions were registered for 838 patients and 824 patients had toxicity > or = grade 1. Bodyweight alteration during treatment was available in 1252 patients; it increased in 153 patients and decreased in 1099 patients. Late toxicities were examined only if they occurred before an eventual tumour failure in order to avoid confusion between effects of first- and second-line treatments. 749 patients were available for analysis of which 646 had late toxicity grade > or = 1. Survival and toxicity were examined in different age ranges from 50 to 75 years and over. There was no significant difference in survival between each age group. A trend test was performed to assess any correlation between age and the acute occurring toxicity. There was no significant difference in acute objective mucosal reactions (P = 0.1) and in weight loss > 10% (P = 0.441). In contrast, older patients had more severe (grade 3 and 4) functional acute toxicity (P < 0.001) than younger patients. We evaluated the probability of late toxicity occurrence in relation to time with the Kaplan-Meier method and the logrank test in each age group. Eighteen per cent of patients were free of late effects at 5 years, the logrank test showing no significant difference between ages (P = 0.84). In conclusion, chronological age is irrelevant for therapeutic decisions.

Concomitant cisplatin and radiotherapy in a conventional and modified fractionation schedule in locally advanced head and neck cancer: a randomised phase II EORTC trial.

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.

Clinical impact of dosimetry quality assurance programmes assessed by radiobiological modelling of data from the thermoluminescent dosimetry study of the European Organization for Research and Treatment of Cancer.

The European Organization for Research and Treatment of Cancer (EORTC) Radiotherapy Group initiated its mailed thermoluminescence dosimetry (TLD) programme in 1986. The aim of the present study was to evaluate the clinical relevance of variations in beam output detected in the period 1993 to 1996. A total of 140 beam outputs were checked (26 for cobalt-60 units and 114 for linear accelerators) in 35 centres. Clinical dose-response data for tumour control and normal tissue morbidity were used to assess the variation in clinical outcome resulting from variability in beam output. For 75 checked beams with nominal accelerating potentials (n. a.p.) of 6 MV or less the mean ratio, +/- standard deviation (S.D.) of measured to stated output was 1.004+/-0.020. For 65 beams with n. a.p. of 8 MV or more, the ratio was 1.009+/-0.021. Even with this relatively high level of precision, broad distributions of estimated tumour control or normal tissue morbidity were found. In the 10% of the beams with the most pronounced underdosage, the loss in tumour control probability was estimated at 7-8 percentage points. Likewise, in the 10% of the beams with the most pronounced overdosage, the increase in mild/moderate morbidity was 19-22 percentage points. For severe morbidity the same beams raised the estimated incidence of severe complications from 5% to 9-10%. An estimation of the loss of uncomplicated cure probability was about 1% for both high and low energy beams. Sequential mailings considerably improved the uniformity of clinical outcome. We conclude that small deviations in beam output may lead to clinically important variations in outcome. Substantial reductions in the variation between measured and stated output can be achieved by sequential mailings. Mailed TLD checks should be an integral part of a continuously ongoing quality assurance activity in radiotherapy.

Patient population analysis in EORTC trial 22881/10882 on the role of a booster dose in breast-conserving therapy.

The changing composition of the patient population in breast cancer, which has been reported over the last decade, has important consequences for prognosis. In the present trial, an analysis of the population in an EORTC trial (22881/10882) on breast-conserving therapy was conducted. A shift towards earlier stages has been seen stage per stage, therefore better survival and local control rates are likely to be expected in comparison to previously published series. The majority of tumours in this trial were small, with a median clinical size of 2 cm and a median pathological size of 1.5 cm. A substantial number of lesions were detected in a pre-clinical stage (17.8%). Nodal involvement was present in only 19% of all patients and usually in only a low number of nodes (only 4% of all patients had four or more nodes invaded). The median number of nodes examined was 12, the difference between institutions was large. There was a significant correlation between the number of nodes examined, the percentage of patients with positive nodes (P = 0.03) and the percentage of patients with massive axillary invasion (P = 0.003). The correlation between clinical evidence and pathological invasion of the axillary nodes showed that 15% of the clinical examinations were false-negative and 51% were false-positive. Pathological nodal invasion could be clinically predicted in only 31% of patients, and consequently clinical examination of the axilla was a poor predictor of prognosis in this study. Pathological invasion of axillary lymph nodes was better correlated to pathological tumour size than clinical or radiological size.

Determination of the optimal dose of 5-fluorouracil when combined with low dose D,L-leucovorin and irradiation in rectal cancer: results of three consecutive phase II studies. EORTC Radiotherapy Group.

In three consecutive phase II trials, 5-fluorouracil (5FU)-low dose leucovorin (20 mg/m2/day) was delivered in two 5-day courses during the first (d1 to d5) and the last (d29 to d33) week of a limited pelvic irradiation (45 Gy, 5 weeks, 25 fractions) in patients with locally extended rectal cancer. The three trials differed only by the 5FU dose in the chemotherapy (CT) schemes. In trial 1 (first CT course 5FU dose 425 mg/m2/day, second CT course 370 mg/m2/day), 16 patients were included. 5 patients suffered a grade 3+ toxicity and the compliance was 63%. In trial 2 (first and second CT course 5FU dose 370 mg/m2/day), 53 patients were included. 5 patients suffered a grade 3+ toxicity. The compliance was 94%. In the trial 3 (first and second CT course 5FU dose 350 mg/m2/day), 16 patients were included. 1 patient suffered a grade 3 toxicity and the compliance was 100%. The overall response rate (complete and partial responses) of local disease and distant metastasis were 87 and 7%, respectively. 43 patients were operated on after a mean delay of 8 weeks. Among the 41 macroscopic complete resections, 6 (14.6%) were sterilised and 12 (29.3%) were classified Asler-Coller A/B1. Regression curve analysis using either grade 3+ toxicity or incomplete treatment as an end point against the 5FU dose indicates that a 350 mg/m2/day 5FU dose is advisable for a phase III adjuvant multicentre trial.

Carcinoma of the cervical stump: a review of 213 cases.

From 1970 to 1987, 213 cases of carcinoma of the cervical stump were accrued in a multi-institutional prospective cooperative study. This group accounted for 5.5% of cervical carcinoma diagnosed during the same period. 13 had in situ carcinoma and 200 had invasive carcinoma (96% squamous cell carcinoma, 4% adenocarcinoma). Radiotherapy alone (external and brachytherapy) was given to 77%, brachytherapy and surgery to 15% and surgery alone to 8%). FIGO stage distribution was: I (31%), IIa (15%), IIb (27%), IIIa (5%), IIIb (17%) and IV (5%). Five-year locoregional control per stage was 100% in Ia, 85% in Ib, 82% in IIa, 71% in IIb, 45% in IIIa, 54% in IIIb and 30% in IV. Corrected 5-year survival per stage was 82% in Ib, 78% in IIa, 73% in IIb, 69% in IIIa, 38% in IIIb and 0% in IV. The diameter of disease in stage II strongly influenced the 5-year locoregional control (81% for tumours of less than 3 cm vs. 68% for tumours more than 3 cm). Lymphangiogram was associated with a 44.5% 5-year locoregional control when positive vs. 74% when non-positive. Brachytherapy was advantageous in obtaining locoregional control in patients receiving external irradiation and brachytherapy: 81.5% vs. 38.5% in patients treated with external radiotherapy alone. Surgery was performed only for in situ carcinoma and for part of stages Ia, Ib and IIa. There is no significant difference in locoregional control at equal stage between radiotherapy alone and treatment schemes including surgery. However, lethal complications were observed in 6% of the patients of the surgical group as compared to 0.6% of the patients treated with radiotherapy alone. Radical radiotherapy seems to provide similar results of locoregional control and survival at equal stages in carcinoma of the cervical stump compared to carcinoma developed on an intact uterus. The rate of severe complications reported with the French-Italian glossary is 13% for G3 and 3% for G4, which is close to the observed rate during the same period in our series of radical radiotherapy to the intact uterus.

The Quality Assurance programme of the Radiotherapy Group of the European Organization for Research and Treatment of Cancer (EORTC): a critical appraisal of 20 years of continuous efforts.

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.

Can patient-, treatment- and pathology-related characteristics explain the high local recurrence rate following breast-conserving therapy in young patients?

The aim of this study was to identify patient-, tumour- or treatment-related factors associated with young age that might explain the higher risk of ipsilateral breast recurrence that occurs after breast-conserving therapy (BCT) in young breast cancer patients. In the 'boost versus no boost trial', 5569 early-stage breast cancer patients were entered. All patients underwent tumorectomy followed by whole breast irradiation of 50 Gy. Patients having a microscopically complete excision were randomised between receiving no boost or a 16-Gy boost, while patients with a microscopically incomplete excision were randomised between receiving a boost dose of 10 or 26 Gy. The 5-year local control rate was 82% for patients 60 years of age (P<0.0001). In young patients, the tumour was significantly larger and more often oestrogen and progesterone receptor-negative. Invasive carcinoma and the intraductal component were more often of a high grade. The intraductal component was more frequently incompletely resected in young patients. Re-excisions were performed more often (most probably due to a more frequent incomplete excision at the first attempt). The total volume of breast tissue removed at the tumorectomy was smaller in the younger patient group, even after including the volume removed during re-excision. When relating all these parameters (including age itself) to local control, the multivariate analysis stratified by treatment showed that age was the only independent prognostic factor for local control (P=0.0001). Including the boost treatment as a separate covariate, the analysis retained age and boost treatment as significant factors related to local control (P<0.0001). It was shown that the boost dose significantly reduced the 5-year local recurrence rate from 7 to 4% for patients with a complete excision (P<0.001). For patients 40 years of age or younger, the boost dose reduced the local recurrence rate from 20 to 10% (P=0.002). This large European Orgnaization for Research and Treatment of Cancer (EORTC) trial demonstrated an increased local recurrence rate in young patients. Although several associations between patient, tumour and treatment factors and age were found, that might explain the high local recurrence rate in the younger patients, it appears that age itself and the boost dose were the only factors that were independently related to local control.

Dosimetric methods in the optimization of radiotherapy for carcinoma of the uterine cervix.

Pelvic failures and late radiation sequelae were analyzed using the dosimetric parameters of ICRU Report 38 for 338 patients with Stage I-III carcinoma of the uterine cervix treated by radiation alone and followed for a minimum of 2 years. The pelvic recurrence rates were: Stage IB 5.1% (N = 118, 1% pelvis alone), Stage IIA 15.1% (N = 53, 9.4% pelvis alone), Stage IIB 15.8% (N = 76, 9.2% pelvis alone) and Stage IIIB 28.9% (N = 76, 17.1% pelvis alone). For Stages I and II pelvic failure was unrelated to cumulated lateral parametrial dose (CDPW) or reference volumes, but for Stage IIIB was higher for CDPW above 65 Gy. Overall complication rates were: grade 3-10.1% and grade 2-18.1% but were much lower for 176 patients treated with stem and ovoids (S + O: grade 3-5.7%, grade 2-15.7%) than for 43 receiving vaginal cylinders (grade 3-37.2%, grade 2-28%). Grade 3 rectal complications associated with cylinders were related to a maximal vaginal application over 1.50 cGy X m2 of total reference air kerma (or 2080 mgh) and cumulated rectal reference doses (CDRref) above 75 Gy. For the S + O group, grade 2 and 3 rectal complications increased with increasing reference volumes (hwt and HWT) and showed dose thresholds for CDRref and CDRmean (grade 3: 75 Gy). Prospective use of zones of risk defined graphically on a dose-volume plot (CDRref vs HWT) has reduced our severe complication rate without reducing local control. This technique requires individualization of patient therapy, rapid access to computerized dosimetry and the establishment of center- and applicator-specific risks of complications.

High dose rate brachytherapy for superficial cancer of the esophagus.

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.

Prognostic factors in limited rectal cancer treated with intracavitary irradiation.

At the Centre Georges-François Leclerc of Dijon, 91 limited rectal tumors received a complete intracavitary 50 kV contact radiotherapy alone or associated with interstitial brachytherapy according to the guidelines of J. Papillon. Nineteen had a villous adenoma and 72 a well or moderately differentiated rectal adenocarcinoma. The majority of patients had contra-indications for major surgical procedures. The median age was 70 years. Seventy-six percent (69/91) of the rectal tumors remained free from local recurrence. After salvage therapy, the local control was 91% (83/91). Sphincter preservation was obtained in 85% (77/91). "De novo" adenocarcinomas developed on pre-existing benign pathology and villous adenomas were not significantly different with regard to local control (76% resp. 75% versus 59.5%; p = 0.22). According to the Dijon clinical staging system, the local relapse-free survival at 5 years was 97% for CS T1A, 77% for CS T1B, 65% for CS T2A, and 60% for CS T2B. Tumors of the anterior rectal wall had a better local control rate than lateral and posterior primaries (100% versus 63% versus 67%). For the middle rectum, the local relapse-free survival was 94% compared to 54% of the upper and 77% of the lower rectum. Four additional patients had a preoperative intracavitary therapy and salvage surgery for incomplete tumor regression; the complete remission rate is 96% (91/95). Intracavitary radiotherapy alone is an effective treatment for limited rectal cancers. Contact X ray therapy can be used alone in CS T1A whereas a combination of contact X ray therapy and interstitial brachytherapy is often the optimal approach in CS T1B and CS T2A. In CS T2B, our data do not support the use of intracavitary techniques alone. In these cases, the sequence external irradiation followed by an interstitial implant seems of interest and deserves further evaluation with more patients and follow-up.