DEGRO practical guidelines: radiotherapy of breast cancer I

Strahlentherapie und Onkologie, Oct 2013

Background and purpose The aim of the present paper is to update the practical guidelines for postoperative adjuvant radiotherapy of breast cancer published in 2007 by the breast cancer expert panel of the German Society for Radiooncology (Deutsche Gesellschaft für Radioonkologie, DEGRO). The present recommendations are based on a revision of the German interdisciplinary S-3 guidelines published in July 2012. Methods A comprehensive survey of the literature concerning radiotherapy following breast conserving therapy (BCT) was performed using the search terms “breast cancer”, “radiotherapy”, and “breast conserving therapy”. Data from lately published meta-analyses, recent randomized trials, and guidelines of international breast cancer societies, yielding new aspects compared to 2007, provided the basis for defining recommendations according to the criteria of evidence-based medicine. In addition to the more general statements of the DKG (Deutsche Krebsgesellschaft), this paper addresses indications, target definition, dosage, and technique of radiotherapy of the breast after conservative surgery for invasive breast cancer. Results Among numerous reports on the effect of radiotherapy during BCT published since the last recommendations, the recent EBCTCG report builds the largest meta-analysis so far available. In a 15 year follow-up on 10,801 patients, whole breast irradiation (WBI) halves the average annual rate of disease recurrence (RR 0.52, 0.48–0.56) and reduces the annual breast cancer death rate by about one sixth (RR 0.82, 0.75–0.90), with a similar proportional, but different absolute benefit in prognostic subgroups (EBCTCG 2011). Furthermore, there is growing evidence that risk-adapted dose augmentation strategies to the tumor bed as well as the implementation of high precision RT techniques (e.g., intraoperative radiotherapy) contribute substantially to a further reduction of local relapse rates. A main focus of ongoing research lies in partial breast irradiation strategies as well as WBI hypofractionation schedules. The potential of both in replacing normofractionated WBI has not yet been finally clarified. Conclusion After breast conserving surgery, no subgroup even in low risk patients has yet been identified for whom radiotherapy can be safely omitted without compromising local control and, hence, cancer-specific survival. In most patients, this translates into an overall survival benefit.

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DEGRO practical guidelines: radiotherapy of breast cancer I

F.Sedlmayer 3 10 M.-L.Sautter-Bihl 1 10 W.Budach 0 10 J.Dunst 7 10 G.Fastner 3 10 P.Feyer 6 10 R.Fietkau 5 10 W.Haase 4 10 W.Harms 9 10 R.Souchon 8 10 F.Wenz 2 10 R.Sauer 5 10 Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO) 10 0 University Hospital Duesseldorf 1 Klinik fr Radioonkologie und Strahlentherapie, Stdtisches Klinikum Karlsruhe 2 University Hospital Mannheim 3 Department of Radiotherapy and Radiation Oncology , LKH Salzburg, Paracelsus Medical University Hospital , Salzburg 4 formerly St.-Vincentius-Kliniken, Karlsruhe 5 University Hospital Erlangen 6 Klinikum Neukoelln, Berlin 7 University Hospital Schleswig-Holstein , Luebeck 8 University Hospital Tbingen 9 St. Clara Hospital , Basel 10 Prof. Dr. F. Sedlmayer Department of Radiotherapy and Radiation Oncology , LKH Salzburg, Paracelsus Medical University Hospital Muellner Haupstr. 48Salzburg Austria Radiotherapy following breast conserving therapy for invasive breast cancer Strahlentherapie und Onkologie 10 2013 | 825 - The evidence for the benefits of postoperative radiotherapy to the whole breast (WBI) has been further substantiated since the last recommendations on the basis of updated meta-analyses, systematic reviews, and randomized controlled trials. Depending on tumor stage, WBI reduces in-breast recurrences as well as regional relapses [23, 24, 27]. To date, there are no conclusive data from prospective clinical investigations about predictive genetic and/or molecular markers on response to radiotherapy Endocrine therapy can reduce or delay locoregional recurrences, however, not distinctive and sustainable enough to compensate the deterioration of local control when WBI is omitted in any age or risk group [27, 68, 77]. Statement RT 1 (Leitlinienprogramm 2012) [74] In invasive breast carcinoma, postoperative radiotherapy following breast conserving surgery has to be performed (LoE 1a, GR A), The EBCTCG meta-analysis 2011 [27] In its recent quinquennial meta-analysis update, the Early Breast Cancer Trialists Collaborative Group (EBCTCG) included 17 randomized studies comparing postoperative radiotherapy vs. none and comprised 7 new studies in addition to previously reported trials. A total of 10,801 patients with pT12 tumors were recorded: the majority of whom (n=7287) were node negative, 1050 were node positive, and in 2464 patients the nodal status was unknown. The effect of radiotherapy on 10-year recurrences of any type and their relation to the 15-year breast cancer death rates were studied in correlation to various prognostic parameters and treatment characteristics. The absolute risk of any first recurrence was adjusted for trial, individual follow-up year, nodal status, and age (five groups), and also for tumor grade, tumor size, estrogen-receptor (ER) status, and whether or not tamoxifen had been used in both randomized groups. Overall, WBI reduced the 10-year recurrence rate (local or distant) from 35 to 19.3%, corresponding to an absolute benefit of 15.7% (2p<0.0001) for irradiated women (pN0: 15.4%, pN+: 21.2%). The Felix Sedlmayer and Marie-Luise Sautter-Bihl contributed equally to the first authorship. 10-year rate of locoregional recurrence as the first event was substantially higher for non-irradiated women: 25.1 vs. 7.7%, i.e., an absolute difference of 17.4% (pN0: 15.5%, pN+: 30.8%). Moreover, WBI decreased the 15-year breast cancer death rate from 25.2 to 21.4%, corresponding to an absolute gain of 3.8% (pN0: 3.3%, pN+: 8.5%). Finally, radiotherapy reduced the 15-year risk of any death from 37.6 to 34.6%, providing an absolute gain of 3.0% (pN0: 2.8%, pN+:10.7%). Mortality without recurrence was slightly but not significantly higher in irradiated women [relative risk (RR) 1.09, 0.971.22, 2p=0.14]. In summary, WBI halved the average annual rate of disease recurrence (RR 0.52, 0.480.56) and reduced the annual breast cancer death rate by about one sixth (RR 0.82, 0.750.90). On average, in all patients, about one breast cancer death was avoided per year 15 for every four recurrences avoided by year 10. Little variation of the proportional benefit was seen in the different prognostic subgroups. In contrast, the absolute benefit from radiotherapy substantially depended on the patient characteristics in terms of prognostic factors. F This important large-scale metaanalysis impressively confirmed that prevention of locoregional recurrences by postoperative radiotherapy translates into improved survival. Radiotherapy in the elderly The indication for WBI for women over 70 years with low risk tumors is an ongoing issue of international debate with partially antipodal interpretations [77]. The updated recommendations of the European Society of Breast Cancer Specialists (EUSOMA) [14] and the latest German S3 guidelines define no age limitation for postoperative RT for healthy elderly patients. Albeit the absolute benefit of adjuvant treatment is smaller in advanced age, the proportional risk (...truncated)


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Prof. Dr. F. Sedlmayer, M.-L. Sautter-Bihl, W. Budach, J. Dunst, G. Fastner, P. Feyer, R. Fietkau, W. Haase, W. Harms, R. Souchon, F. Wenz, R. Sauer, Breast Cancer Expert Panel of the German Society of Radiation Oncology (DEGRO). DEGRO practical guidelines: radiotherapy of breast cancer I, Strahlentherapie und Onkologie, 2013, pp. 825-833, Volume 189, Issue 10, DOI: 10.1007/s00066-013-0437-8