Toxicity at three years with and without irradiation of the internal mammary and medial supraclavicular lymph node chain in stage I to III breast cancer (EORTC trial 22922/10925).

INTRODUCTION: The EORTC 22922/10925 trial investigated the potential survival benefit and toxicity of elective irradiation of the internal mammary and medial supraclavicular (IM-MS) nodes Accrual completed in January 2004 and first results are expected in 2012. We present the toxicity reported until year 3 after treatment. PATIENTS AND METHODS: At each visit, toxicity was reported but severity was not graded routinely. Toxicity rates and performance status (PS) changes at three years were compared by chi(2) tests and logistic regression models in all the 3,866 of 4,004 patients eligible to the trial who received the allocated treatment. RESULTS: Only lung (fibrosis; dyspnoea; pneumonitis; any lung toxicities) (4.3% vs. 1.3%; p < 0.0001) but not cardiac toxicity (0.3% vs. 0.4%; p = 0.55) significantly increased with IM-MS treatment. No significant worsening of the PS was observed (p = 0.79), suggesting that treatment-related toxicity does not impair patient's daily activities. CONCLUSIONS: IM-MS irradiation seems well tolerated and does not significantly impair WHO PS at three years. A follow-up period of at least 10 years is needed to determine whether cardiac toxicity is increased after radiotherapy.

Quality assurance in the 22991 EORTC ROG trial in localized prostate cancer: dummy run and individual case review.

INTRODUCTION: EORTC trial 22991 was designed to evaluate the addition of concomitant and adjuvant short-term hormonal treatments to curative radiotherapy in terms of disease-free survival for patients with intermediate risk localized prostate cancer. In order to assess the compliance to the 3D conformal radiotherapy protocol guidelines, all participating centres were requested to participate in a dummy run procedure. An individual case review was performed for the largest recruiting centres as well. MATERIALS AND METHODS: CT-data of an eligible prostate cancer patient were sent to 30 centres including a description of the clinical case. The investigator was requested to delineate the volumes of interest and to perform treatment planning according to the protocol. Thereafter, the investigators of the 12 most actively recruiting centres were requested to provide data on five randomly selected patients for an individual case review. RESULTS: Volume delineation varied significantly between investigators. Dose constraints for organs at risk (rectum, bladder, hips) were difficult to meet. In the individual case review, no major protocol deviations were observed, but a number of dose reporting problems were documented for centres using IMRT. CONCLUSIONS: Overall, results of this quality assurance program were satisfactory. The efficacy of the combination of a dummy run procedure with an individual case review is confirmed in this study, as none of the evaluated patient files harboured a major protocol deviation. Quality assurance remains a very important tool in radiotherapy to increase the reliability of the trial results. Special attention should be given when designing quality assurance programs for more complex irradiation techniques.

Quality assurance in the EORTC phase III randomised 'boost vs. no boost' trial for breast conserving therapy: comparison of the results of two individual case reviews performed early and late during the accrual period.

BACKGROUND AND PURPOSE: To evaluate the impact of quality assurance on treatment compliance, we compared the outcome of the two individual case reviews (ICR) conducted early and late during the accrual period of a large prospective multi-centre trial. PATIENTS AND METHODS: At the onset of the trial, medical files of five patients from each participating centre were evaluated for the compliance to the protocol for eligibility, surgery, pathology and radiotherapy and for the quality of reporting of the data on the case report forms. In nine major centres, this procedure was repeated near the end of the trial. RESULTS: Both in the early and the late ICR, we found a very limited number of deviations from the guidelines for eligibility, staging, surgery, and pathology. Compliance to radiotherapy requirements was good with the exception of a too low minimal dose in 30% and the lack of target volume delineation in the majority of the evaluated patients. The comparison of the late with the early ICR demonstrated an improvement of the quality of data reporting by 6% and of target volume delineation from 33 to 53%. CONCLUSIONS: The initial ICR has lead to the identification of a number of parameters, which needed a clarification in the protocol. These items have been corrected and the individual institutions have been made aware of the necessary adaptations. The evaluation at the end of the trial period showed that there was an improvement but also showed that continuous monitoring is necessary, especially for institutions which have the most deviations in the first ICR.

Quality assurance of the EORTC 26981/22981; NCIC CE3 intergroup trial on radiotherapy with or without temozolomide for newly-diagnosed glioblastoma multiforme: the individual case review.

The phase III randomised European Organisation for Research and Treatment of Cancer (EORTC) and National Cancer Institute of Canada Clinical Trail Group (NCIC) Intergroup trial (EORTC 26981/22981; CE3) compares irradiation alone with irradiation plus temozolomide for patients with glioblastoma multiforme (GBM). We evaluated the compliance to radiotherapy (RT) guidelines. All 85 recruiting centres were invited to participate in the individual case review. Fifty-four centres (64%) entering 71% of the patients provided data on one randomly selected patient. All participating centres used individual head immobilisation and computerised tomography (CT)-based treatment planning. Most (74%) performed three-dimensional conformal radiotherapy (3-D-CRT) including dose-volume histograms. Ninety-four percent performed portal imaging at least once. Planning target volume (PTV) and structures at risk were delineated in most of the centres (94%). Although the PTV received < 95% of the prescription dose (60 Gy in 2 Gy/fraction/day) in 39% of the centres; all except 2 centres delivered 50-60 Gy to the PTV. The maximum dose to the critical structures exceeded the protocol dose constraints in 39% of the reviewed patients, but in only 9% was this over the acceptable tolerance dose reported in the literature. We found a high rate of compliance with the protocol and general RT guidelines in the centres participating in this individual case review. In multicentre trials with a large of number of investigators from international and national groups, it is essential to confirm the interinstitutional consistency, qualitatively and quantitatively.

High conformality radiotherapy in Europe: thirty-one centres participating in the quality assurance programme of the EORTC prostate trial 22991.

Today, conformality in radiotherapy is at the centre of many investments in equipment and staffing. To estimate the current situation within the European Organisation for Research and Treatment of Cancer (EORTC) conformal radiotherapy trial for prostate cancer, a technology questionnaire was designed to assess whether participating centres can comply with the required radiotherapy procedures of EORTC trial 22991, where a high dose is prescribed to the prostate. Questions covered various items of computed tomography, data acquisition, treatment planning, delivery and verification. All centres (n=31) replied to the questionnaire. All generate beam's eye views and dose volume histograms. All, but two, centres use digitally reconstructed radiographs to display images. The vast majority of the centres perform at least weekly treatment verification and half have access to individual in vivo dosimetry. The results of the questionnaire indicate that participating centres have access to the equipment and apply the procedures that are essential for conformal prostate radiotherapy. The technology questionnaire is the first step in the extensive quality assurance programme dedicated to this high-tech radiotherapy trial.

Late toxicity following conventional radiotherapy for prostate cancer: analysis of the EORTC trial 22863.

Late toxicity and other serious adverse events (SAE) were analysed in the European Organisation for Research and Treatment of Cancer (EORTC) trial 22863. The study evaluated the value of adjuvant endocrine treatment for locally advanced prostate cancer treated with radiotherapy. From 1987 to 1995, 415 patients were randomised. There was long-term toxicity information for 377 patients (91%). Median age was 70 years (range 50-80 years). Median follow-up for late toxicity was 42 months (range 3-136 months). Toxicity was graded according to a modified Radiotherapy and Oncology Group (RTOG) scale. Other late SAE, that was not classified as severe treatment toxicity, but were still life-threatening, were also assessed. There were 72 patients with grade 2, 10 patients with grade 3 and 4 patients with grade 4 toxicity. There were 20 patients with other late SAE, who were grouped according to their relationship to treatment; likely related (n = 1), unrelated (n = 7) and not assessable (n = 12). Although four treatment-related deaths (1%) occurred, grade 3 or 4 late complications were less than 5%.