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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.

Purpose: To assess the impact of the boost dose in patients with involved surgical margins., Patients and Methods: In the EORTC "boost versus no boost" trial, 251 patients with a microscopically incomplete tumour excision were randomised to receive either a low boost dose of 10 Gy (126 patients) or a high boost dose of 26 Gy (125 patients). Overall survival and the cumulative incidence of local recurrence as first event were compared by Logrank and Gray test, respectively (2-sided alpha=0.05), with a median follow-up of 11.3 years. The planned sample size was 660 patients, but only 251 were recruited., Results: The median age at randomisation was 54 years. Thirty-seven patient initially relapsed locally. At 10 years, the cumulative incidence of local recurrence was 17.5% (95% CI: 10.4-24.6%) versus 10.8% (95% CI: 5.2-16.4%) for the low and high boost dose groups, respectively (HR=0.83, 95% CI: 0.43-1.57, Gray p>0.1). Overall, 64 patients have died (25.5%), 47 of them of breast cancer, without a difference in duration of survival between the two groups (HR=0.97, 95% CI=0.59-1.5, p>0.1). Severe fibrosis was palpated in the breast in 1% versus 5% and in the boost area in 3% versus 13% in the low and high boost dose groups, respectively., Conclusions: There was no statistically significant difference in local control or survival between the high boost dose of 26 Gy and the low boost dose of 10 Gy in patients with microscopically incomplete excision of early breast cancer. Fibrosis, however, was noted significantly more frequently in cases treated with the high boost dose.

Purpose: To investigate the long-term impact of a boost radiation dose of 16 Gy on local control, fibrosis, and overall survival for patients with stage I and II breast cancer who underwent breast-conserving therapy., Patients and Methods: A total of 5,318 patients with microscopically complete excision followed by whole-breast irradiation of 50 Gy were randomly assigned to receive either a boost dose of 16 Gy (2,661 patients) or no boost dose (2,657 patients), with a median follow-up of 10.8 years., Results: The median age was 55 years. Local recurrence was reported as the first treatment failure in 278 patients with no boost versus 165 patients with boost; at 10 years, the cumulative incidence of local recurrence was 10.2% versus 6.2% for the no boost and the boost group, respectively (P < .0001). The hazard ratio of local recurrence was 0.59 (0.46 to 0.76) in favor of the boost, with no statistically significant interaction per age group. The absolute risk reduction at 10 years per age group was the largest in patients

The EORTC 22922/10925 trial randomly compares irradiation or no irradiation of the internal mammary and medio supraclavicular (IM-MS) nodes for stage I-III breast cancer. We report on the characteristics of 4004 participating patients, aspects of quality assurance and compliance to protocol treatment. The actual population has intermediate-risk disease: 51.8% stage II, 56% positive axillary nodes. The allocated treatment was not followed in 3.2% in the IM-MS irradiation arm versus 2% in the no IM-MS irradiation arm. In the IM-MS arm, there were major deviations for dose in 0.8%, surgery-to-radiotherapy time interval in 3.9% and in overall treatment time in 0.9% cases. Major deviations were found in 7.9% patients in the IM-MS group and in 2% patients in the no IM-MS group. In the final trial analysis, a sensitivity analysis should evaluate the subgroup of patients receiving an optimal treatment to verify the robustness of the results and the true impact of IM-MS irradiation.

Purpose: To determine whether the effect of an additional "boost" radiation after breast conservative therapy (BCT) on local control depends on age and evaluate the impact of a treatment policy with a threshold for age., Patients and Methods: We used data from EORTC 22881-10882 trial, with median follow-up of 77.4 months. Patients receiving BCT and 50Gy whole breast irradiation were randomized to no boost and 16Gy boost (N=5318)., Results: In univariate analysis, a boost reduced local failure by a factor of 2 (P<0.0001). Multivariate analysis showed local control increased with age (P=0.0003). There was no evidence that the relative effect of a boost on local control depends on age (P=0.97) However in younger patients the 5-year local failure was higher, therefore the absolute reduction was greater. If the threshold-age for boost treatment were set at 40 years, 8.4% of the study population would receive a boost, resulting in a 5-year local failure of 6.1% in the study population. Changing the threshold-age to 60 years, 67% of the study population would receive a boost and the 5-year local failure would be reduced to 4.4%., Conclusions: In younger patients a boost dose resulted in a greater absolute reduction of local failure. The relative risk reduction was however similar for all ages. Applying a treatment policy with a threshold-age of 60 would result in 0.6% increase in local failure in the total study population, while sparing the boost to 1/3 of the patients.

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.

Background and Purpose: The EORTC Trial 22881/10882 investigating the role of a boost dose in breast conserving therapy demonstrated a significantly better local control rate with the higher radiotherapy dose, especially in women younger than 50 years of age. This paper investigates the potential impact of the different boost techniques on local control and on fibrosis after breast conserving therapy., Patients and Methods: From 1989 to 1996, 2661 patients were randomised to receive a boost dose of 16Gy to the primary tumour bed after microscopically complete tumorectomy and 50Gy whole breast irradiation. The choice of the boost technique was left to the treating investigator. Treatment data were prospectively recorded as well as the clinical outcome in terms of local control and fibrosis. Sixty-three percent of the patients received a boost dose with fast electrons, 28% with photon beams and 9% with interstitial brachytherapy., Results: At 5 years, local recurrences were seen in 74 of the 1635 patients who received an electron boost (4.8%, CI 3.6-5.9%), in 28 of the 753 patients who received a photon boost (4.0%, CI 3.4-5.5%) and in 6 of the 225 patients after an interstitial boost (2.5%, CI 0.3-4.6%). The grade of fibrosis in the whole breast as well as at the primary tumour bed, as scored by the treating radiation oncologist, was similar in the three groups., Conclusions: Although the three groups are of a rather unequal size, the results of the interstitial boost seem similar in terms of fibrosis and at least as good in terms of local control, despite a lower treatment volume and a longer overall treatment time.