Breast Neoplasms: Sauer R

Sautter-Bihl ML, Souchon R, Budach W, Sedlmayer F, Feyer P, Harms W, Haase W, Dunst J, Wenz F, Sauer R. · Municipal Hospital Karlsruhe, Karlsruhe, Germany. · Strahlenther Onkol. · Pubmed #19016032 No free full text.

Abstract: BACKGROUND AND PURPOSE: The aim of the present paper is to update the practical guidelines for radiotherapy of breast cancer published in 2006 by the breast cancer expert panel of the German Society for Radiooncology (DEGRO). These recommendations were complementing the S3 guidelines of the German Cancer Society (DKG) elaborated in 2004. The present DEGRO recommendations are based on a revision of the DKG guidelines provided by an interdisciplinary panel and published in February 2008. METHODS: The DEGRO expert panel (authors of the present manuscript) performed a comprehensive survey of the literature. Data from lately published meta-analyses, recent randomized trials and guidelines of international breast cancer societies, yielding new aspects compared to 2006, provided the basis for defining recommendations referring to the criteria of evidence-based medicine. In addition to the more general statements of the DKG, this paper emphasizes specific radiooncologic issues relating to radiotherapy after mastectomy (PMRT), locally advanced disease, irradiation of the lymphatic pathways, and sequencing of local and systemic treatment. Technique, targeting, and dose are described in detail. RESULTS: PMRT significantly reduces local recurrence rates in patients with T3/T4 tumors and/or positive axillary lymph nodes (12.9% with and 40.6% without PMRT in patients with four or more positive nodes). The more local control is improved, the more substantially it translates into increased survival. In node-positive women the absolute reduction in 15-year breast cancer mortality is 5.4%. Data referring to the benefit of lymphatic irradiation are conflicting. However, radiotherapy of the supraclavicular area is recommended when four or more nodes are positive and otherwise considered individually. Evidence concerning timing and sequencing of local and systemic treatment is sparse; therefore, treatment decisions should depend on the dominating risk of recurrence. CONCLUSION: There is common consensus that PMRT is mandatory for patients with T3/T4 tumors and/or four or more positive axillary nodes and should be considered for patients with one to three involved nodes. Irradiation of the lymphatic pathways and the optimal time point for onset of radiotherapy are still under debate.

Sautter-Bihl ML, Budach W, Dunst J, Feyer P, Haase W, Harms W, Sedlmayer F, Souchon R, Wenz F, Sauer R, Anonymous00109, Anonymous00110. · Municipal Hospital Karlsruhe, Germany. · Strahlenther Onkol. · Pubmed #18040609 No free full text.

Abstract: BACKGROUND: The present paper is an update of the practical guidelines for radiotherapy of breast cancer published in 2006 by the breast cancer expert panel of the German Society of Radiation Oncology (DEGRO) [34]. These recommendations have been elaborated on the basis of the S3 guidelines of the German Cancer Society that were revised in March 2007 by an interdisciplinary panel [18]. METHODS: The DEGRO expert panel performed a comprehensive survey of the literature, comprising lately published meta-analyses, data from recent randomized trials and guidelines of international breast cancer societies, referring to the criteria of evidence- based medicine [25]. In addition to the more general statements of the German Cancer Society, this paper emphasizes specific radiotherapeutic aspects. It is focused on radiotherapy after breast-conserving surgery. Technique, targeting, and dose are described in detail. RESULTS: Postoperative radiotherapy significantly reduces rates of local recurrence. The more pronounced the achieved reduction is, the more substantially it translates into improved survival. Four prevented local recurrences result in one avoided breast cancer death. This effect is independent of age. An additional boost provides a further absolute risk reduction for local recurrence irrespective of age. Women > 50 years have a hazard ratio of 0.59 in favor of the boost. For DCIS, local recurrence was 2.4% per patient year even in a subgroup with favorable prognostic factors leading to premature closure of the respective study due to ethical reasons. For partial-breast irradiation as a sole method of radiotherapy, results are not yet mature enough to allow definite conclusions. CONCLUSION: After breast-conserving surgery, whole-breast irradiation remains the gold standard of treatment. The indication for boost irradiation should no longer be restricted to women <or= 50 years. Partial-breast irradiation is still an experimental treatment and therefore discouraged outside controlled clinical trials. Omission of radiotherapy after breast-conserving surgery of DCIS should be restricted to individual exceptions.

Sautter-Bihl ML, Sauer R. · No affiliation provided · Strahlenther Onkol. · Pubmed #17609867 No free full text.

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Souchon R, Budach W, Dunst J, Feyer P, Haase W, Harms W, Sautter Bihl ML, Wenz F, Sauer R, Anonymous00094. · No affiliation provided · Strahlenther Onkol. · Pubmed #16896587 No free full text.

This publication has no abstract.

Sautter-Bihl ML, Sauer R. · No affiliation provided · Strahlenther Onkol. · Pubmed #16622620 No free full text.

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Sauer R, Wenz F, Strnad V, Haase W, Souchon R, Sautter-Bihl ML. · No affiliation provided · Strahlenther Onkol. · Pubmed #15995834 No free full text.

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Sauer R, Sautter-Bihl ML, Budach W, Feyer P, Harms W, Souchan R, Wollwiener D, Kreienberg R, Wenz F. · Department of Radiation Oncology, University of Erlangen, Erlangen, Germany. · Cancer. · Pubmed #17647249 links to  free full text

Abstract: BACKGROUND: Breast-conserving surgery followed by whole-breast radiotherapy (WBRT) has become the standard treatment for the majority of patients with early breast cancer. Whereas the indications for systemic adjuvant treatment have continuously expanded, there is a tendency to restrict postoperative radiotherapy to accelerated partial breast irradiation (APBI) instead of WBRT. METHODS: The different techniques of APBI are described and their respective advantages or potential drawbacks outlined. Moreover, the results described in the literature are briefly reviewed as a basis for the consensus statements and recommendations of the German Society of Radiation Oncology, the German Society of Senology, and the Working Group for Gynecological Oncology of the German Cancer Society. RESULTS: The methods mainly used for APBI are: interstitial radiotherapy with multicatheter technique, intraoperative radiotherapy (IORT) using either electrons produced by linear accelerators or 50 kV x-rays (Intrabeam), the balloon-catheter technique (MammoSite), or 3D conformal external beam radiotherapy. These techniques have marked differences in dose distribution and homogeneity. The published range of local recurrence rates varies between 0% to 37%, the median follow-up from 8 to 72 months. CONCLUSIONS: To date, follow-up times mostly do not yet permit a definite judgment concerning the long-term effectiveness and side effects of APBI. The relevant societies in Germany support randomized clinical studies comparing APBI with WBRT in a well-defined subset of low-risk patients. However, the authors expressly discourage the routine use of APBI outside clinical trials. Until definite results show that APBI neither impairs therapeutic outcome nor cosmetic results, WBRT remains the gold standard in the treatment of early breast cancer.

Sauer G, Strnad V, Kurzeder C, Kreienberg R, Sauer R. · Department of Gynecology, University of Ulm, Germany. · Strahlenther Onkol. · Pubmed #15660187 No free full text.

Abstract: BACKGROUND: The standard technique of postoperative radiotherapy after breast-conserving surgery is percutaneous irradiation of the entire breast to a total dose of 45-50 Gy which is usually followed by a tumor bed boost. Since the majority of local recurrences in selected patients occur close to the former tumor bed, the question arises whether a sole tumor bed irradiation might be a therapeutic alternative to total breast irradiation. METHODS: A systematic review of relevant literature concerning partial breast irradiation (PBI) up to November 2004 was undertaken. Studies of any design were included for comparison and discussion. RESULTS: Nine unique brachytherapy studies using the multi-catheter technique, one the balloon technique (MammoSite), and eight particular intraoperative radiotherapy (IORT) trials were located of which only one was a randomized trial. Only minor postoperative complications were reported. Preliminary results are similar in terms of local tumor control, disease-free and overall survival. However, the current evidence base of IORT studies is poor. CONCLUSION: Despite controversies regarding PBI after breast-conserving surgery, results of phase I-II trials suggest that sole tumor bed irradiation might be an appropriate therapeutic alternative for selected breast cancer patients. However, more experience and data from ongoing phase III trials are required to define these new methods to be an appropriate treatment option. Therefore, total breast irradiation still remains the standard irradiation modality even in the treatment of early breast cancer, and PBI should be considered investigational.

Sauer R, Schulz KD, Hellriegel KP, Anonymous00104. · Klinik für Strahlentherapie, Friedrich-Alexander-Universität, Erlangen-Nürnberg. · Strahlenther Onkol. · Pubmed #11200107 No free full text.

Abstract: BACKGROUND: Recent publications of the Danish Breast Cancer Cooperative Group together with data from the British Columbia Trial have stirred major discussions concerning the role of radiation therapy after mastectomy. Different treatment approaches are to be found even within the same cancer center. The German Society of Senology, a cooperative group of all medical disciplines involved in the treatment of breast cancer, has therefore worked out a consensus statement. MATERIAL AND METHOD: The recently published literature and experts opinions, in particular randomized studies since 1997, meta-analyses from the Early Breast Cancer Trialists' Collaborative Group, epidemiological investigations with regard to the time course of distant metastases in breast cancer as well as the current consensus of the American Society for Therapeutic Radiology and Oncology served as the basis for discussion and consulting. RESULTS OF THE CONSENSUS: (1) An optimally performed mastectomy is a major prerequisite for tumor cure. Radical (R0) resection of the tumor as well as dissection of at least 10 lymph nodes from the axillary level I and II should be accomplished. If axillary lymph nodes are involved, the surgical removal of these lymph nodes is not only of diagnostic, but also of therapeutic value, as it reduces the risk for locoregional relapses. (2) Most probably, locoregional relapses do not only indicate, but are also a source for distant metastases. (3) Radiation therapy of the chest wall and the regional lymph nodes increases the overall survival in risk patients and reduces the risk of locoregional relapses. Moreover, radiation therapy improves the prognosis in case of residual tumor or an incomplete axillary dissection. Unequivocal and reasonable indications for radiation therapy after mastectomy include T3/T4-carcinoma, T2-carcinoma > 3 cm, multicentric tumor growth, lymphangiosis carcinomatosa or vessel involvement, involvement of the pectoralis fascia or a safety margin < 5 mm, R1- or R2 resection and more than 3 axillary lymph node metastases. Further reasonable indications, albeit not yet evaluated in clinical trials, include multifocality, extensive intraductal component, negative hormone receptor status, G3-differentiation grade, diffuse micro-calcifications, 1 to 3 axillary lymph node metastases, multiple, non-complete biopsies and age < 35 years. (4) An endocrine therapy with tamoxifen concurrent to radiation therapy is also reasonable--despite some contradictory in-vitro data--as it enhances the apoptotic cell death. The CMF-regimen is usually performed as sandwich procedure, but can also be applied concurrently to radiation therapy, if indicated. Conversely, an anthracycline-containing chemotherapy should be finished prior to postoperative radiation therapy. CONCLUSIONS: Adjuvant radiation therapy after mastectomy improves the 10-year-survival probability up to 10%, at least for risk patients. The hypotheses of Halsted and Fisher do not exclude each other. There are patients, in which the one, and there are patients, in which the other hypothesis applies.

Sauer R. · Klinik und Poliklinik f]ur Strahlentherapie, Universit]atsklinikum, D-91054, Erlangen, Germany. · Eur J Cancer. · Pubmed #10854937 No free full text.

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Ott OJ, Hildebrandt G, Pötter R, Hammer J, Lotter M, Resch A, Sauer R, Strnad V. · University Hospital Erlangen, Department of Radiation Oncology, Erlangen, Germany. · Radiother Oncol. · Pubmed #17126940 No free full text.

Abstract: BACKGROUND AND PURPOSE: To evaluate the safety and effectiveness of accelerated partial breast irradiation (APBI) with multi-catheter brachytherapy. PATIENTS AND METHODS: Between 11/2000 and 04/2005, 274 patients participated. Patients were eligible for APBI if they had histologically confirmed breast cancer, a tumour diameter 3cm, complete resection with clear margins 2mm, negative axillary lymph nodes or singular nodal micro-metastasis, no distant metastases, hormone receptor-positive tumours, and were >/= 35 years. Patients were excluded if mammographically they showed a multicentric invasive growth pattern, poorly differentiated tumours, residual diffuse micro-calcifications, extensive intraductal component, or vessel invasion. Median follow-up was 32 months (range; 8-68). RESULTS: The local control rate was 99.3% (272/274), the 3 year-local-recurrence-free survival probability, 99.6%. Peri-operative complications occurred in 5.5% (15/274): 9 (3.3%) experienced implant infection and 6 (2.2%) hematoma. Acute toxicity (Grade 1/2 radio-dermatitis) was seen in 6.6% (18/274). Late side effects >/= Grade 3 (fibrosis, telangiectasia) occurred in 1.8% (4/274). Cosmetic results were excellent/good in 94% (253/274). CONCLUSIONS: This analysis underlined the safety and effectiveness of APBI in a carefully selected subgroup with favourable disease characteristics. Of course, longer follow-up and randomised trials are necessary to conclusively assess the potential of APBI.

Ott OJ, Pötter R, Hildebrandt G, Hammer J, Lotter M, Beckmann MW, Sauer R, Strnad V. · Strahlenklinik, Universitätsklinikum Erlangen, Deutschland. · Rofo. · Pubmed #15973598 No free full text.

Abstract: PURPOSE: To evaluate perioperative morbidity, toxicity and cosmetic outcome in patients treated with interstitial brachytherapy to the tumor bed as the sole radiation modality after breast conserving surgery. MATERIALS AND METHODS: From 11/2000 to 11/2004, 240 women with early stage breast cancer participated in a protocol of tumor bed irradiation alone using pulsed dose rate (PDR) or high dose rate (HDR) interstitial multi-catheter implants (partial breast irradiation). Perioperative morbidity, acute and late toxicity as well as cosmetic outcome were assessed. Of the first 51 patients treated in this multicenter trial, we present interim findings after a median follow-up of 36 months. RESULTS: Perioperative Morbidity: Bacterial infection of the implant: 2 % (1/51). Acute toxicity: radiodermatitis Grade 1: 4 % (2/51). Late toxicity: breast pain Grade 1: 8 % (4/51), Grade 2: 2 % (1/51); dyspigmentation Grade 1: 8 % (4/51); fibrosis Grade 1: 4 % (2/51), Grade 2: 8 % (4/51); telangiectasia Grade 1: 10 % (5/51), Grade 2: 4 % (2/51). Cosmetic results: Excellent and good in 94 % (48/51) of the patients. CONCLUSION: This analysis indicates that accelerated partial breast irradiation with 192-iridium interstitial multicatheter PDR-/HDR-implants (partial breast irradiation) is feasible with low perioperative morbidity, low acute and mild late toxicity at a median follow-up of 36 months. The cosmetic result is not significantly affected.

Strnad V, Ott O, Pötter R, Hildebrandt G, Hammer J, Resch A, Lotter M, Ackermann S, Beckmann MW, Sauer R. · Department of Radiation Oncology, Erlangen-Nürnberg University, Universitätstr. 27, 91052 Erlangen, Germany. · Brachytherapy. · Pubmed #15533801 No free full text.

Abstract: PURPOSE: To evaluate the value of interstitial brachytherapy (iBT) alone in the treatment of low-risk breast cancer patients with regard to local control, side effects, and cosmesis. METHODS AND MATERIALS: From November 2000 to January 2004, 176 patients with low-risk breast cancer were treated with iBT only. Patients were eligible for entering the study if: the tumor size was <3 cm; resection margins were clear by at least 2 mm; there were no lymph node metastases or only one micrometastasis (pNo, pNmi); age was >35 years; steroid hormone receptor was positive; and histologic grade was 1 or 2. Seventy-five percent of patients received pulsed-dose-rate brachytherapy (D(ref) = 50 Gy); 25% of patients received high-dose-rate brachytherapy (D(ref) = 32.0 Gy). An interim analysis is presented for all patients after an interim follow-up of 12 months, and for half the patient population with an interim follow-up of 21 months. RESULTS: All patients remained disease-free on the date of analysis. A perioperative complication breast infection was recorded for 1/176 (0.6%) patients. Late toxicity i.e., hypersensation, hyperpigmentation, fibrosis, or teleangiectasia was observed in 1-12% of all patients. Grade I Fibrosis was registered in 7.6% (13/172) and grade II in 7.0% (12/172) of evaluable patients. Similarly, grade I teleangiectasia was observed in 4.7% (8/172), grade II in 0.6% (1/172), and grade III also in 0.6% (1/172) of evaluable patients. Excellent or good cosmetic results have been observed in 92-95% of patients. CONCLUSIONS: Brachytherapy as monotherapy in low-risk breast cancer patients after breast-conserving surgery is an effective, precise treatment modality without perioperative morbidity, low acute, mild late toxicity, and yields good to excellent cosmetic results.

Ott OJ, Pötter R, Hammer J, Hildebrandt G, Lotter M, Resch A, Pöhls U, Beckmann MW, Sauer R, Strnad V. · Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany. · Strahlenther Onkol. · Pubmed #15480513 No free full text.

Abstract: PURPOSE: To evaluate perioperative morbidity, toxicity, and cosmetic outcome in patients treated with interstitial brachytherapy to the tumor bed as the sole irradiation modality after breast-conserving surgery. PATIENTS AND METHODS: From November 1, 2000 to January 31, 2004, 176 women with early-stage breast cancer became partakers in a protocol of tumor bed irradiation alone using pulsed-dose-rate (PDR) or high-dose-rate (HDR) interstitial multicatheter implants. Patients became eligible, if their tumor was an infiltrating carcinoma < or = 3 cm in diameter, the surgical margins were clear by at least 2 mm, the axilla was surgically staged node-negative, the tumor was estrogen and/or progesterone receptor-positive, well or moderately differentiated (G1/2), the tumor did not contain an extensive intraductal component (EIC) and the patient's age was > 35 years. Implants were positioned using a template guide, delivering either 49.8 Gy in 83 consecutive hours (PDR) or 32.0 Gy in two daily fractions over 4 days (HDR). Perioperative morbidity, toxicity, and cosmetic outcome were assessed. Interim findings of the first 69 patients, who were treated in this multicenter trial, after a median follow-up of 24 months (range, 15-39 months) are presented. RESULTS: One of the 69 patients (1.4%) developed a bacterial infection of the implant. No other perioperative complications, for example bleeding or hematoma, were observed. Acute toxicity was low: 2.9% of the patients (2/69) experienced mild radiodermatitis. Late toxicity: hypersensation/mild pain 7.2% (5/69), intermittent but tolerable pain 1.4% (1/69), mild dyspigmentation 10.1% (7/69), mild fibrosis 11.6% (8/69), moderate fibrosis 1.4% (1/69), mild telangiectasia (< 1 cm(2)) 11.6% (8/69), and moderate teleangiectasia (1-4 cm(2)) 1.4% (1/69). Good to excellent cosmetic results were observed in 92.4% of the patients evaluated. All patients (n = 176) remained disease-free to the date of evaluation. CONCLUSION: This analysis indicates that accelerated partial breast irradiation with iridium-192 interstitial multicatheter PDR/HDR implants is feasible with low perioperative morbidity, low acute and mild late toxicity, and does not significantly affect cosmetic results at a median follow-up of 24 months.

Winzer KJ, Sauer R, Sauerbrei W, Schneller E, Jaeger W, Braun M, Dunst J, Liersch T, Zedelius M, Brunnert K, Guski H, Schmoor C, Schumacher M, Anonymous00271. · Department of Surgery, Universitätsklinikum Charité Berlin, Germany. · Eur J Cancer. · Pubmed #15093574 No free full text.

Abstract: To study the role of radiotherapy and tamoxifen after breast-conserving surgery (BCS) in patients with a favourable prognosis, a clinical trial was initiated by the German Breast Cancer Study Group. Between 1991 and 1998, 361 patients (pT1pN0M0, aged 45-75 years, receptor positive, grade I-II) were randomised to radiotherapy (yes/no) and tamoxifen for 2 years (yes/no) in a 2x2 factorial design; the exclusion of seven centres (14 patients) left 347 patients in the analysis. After a median follow-up of 5.9 years, 77 events concerning event-free survival have been observed. Since a strong interactive effect between radiotherapy and tamoxifen has been established, the results are presented in terms of the treatment effects for all four treatment groups separately. Mainly due to the presence of local recurrences, the event rate was about three times higher in the group with BCS only than in the other three groups. No difference could be established between the four treatment groups for distant disease-free survival rates. It is concluded that even in patients with a favourable prognosis, the avoidance of radiotherapy and tamoxifen after BCS increases the rate of local recurrences substantially.

Ott OJ, Lotter M, Sauer R, Strnad V. · Department of Radiation Oncology, University Hospital Erlangen, Erlangen, Germany. · Strahlenther Onkol. · Pubmed #17680222 No free full text.

Abstract: PURPOSE: To describe relative skin dose estimations and their impact on cosmetic outcome in interstitial multicatheter accelerated partial-breast irradiation (APBI). PATIENTS AND METHODS: Between April 2001 and January 2005, 105 consecutive patients with early breast cancer were recruited in Erlangen, Germany, for this substudy of the German-Austrian APBI phase II trial. 51% (54/105) received pulsed-dose-rate (PDR), and 49% (51/105) high-dose-rate (HDR) brachytherapy. Prescribed reference dose for HDR brachytherapy was 32 Gy in eight fractions of 4 Gy, twice daily. Prescribed reference dose in PDR brachytherapy was 49.8 Gy in 83 consecutive fractions of 0.6 Gy every hour. Total treatment time was 3-4 days. With a wire cross on the skin surface during the brachytherapy-planning procedure the minimal, mean and maximal relative skin doses (SD(min%), SD(max%), SD(mean%)) were recorded. Endpoint of this evaluation was the cosmetic outcome in relation to the relative skin doses. RESULTS: Median follow-up time was 38 months (range, 19-65 months). Cosmetic results for all patients were excellent in 57% (60/105), good in 36% (38/105), and fair in 7% (7/105). The SD(min%) (27.0% vs. 31.7%; p = 0.032), SD(mean%) (34.2% vs. 38.1%; p = 0.008), and SD(max%) (38.2% vs. 46.4%; p = 0.003) were significantly lower for patients with excellent cosmetic outcome compared to patients with a suboptimal outcome. SD(mean%) (37.6% vs. 34.2%; p = 0.026) and SD(max%) (45.4% vs. 38.2%; p = 0.008) were significantly higher for patients with good cosmetic outcome compared with the patients with excellent results. CONCLUSION: The appraisal of skin doses has been shown to be relevant to the achievement of excellent cosmetic outcome. Further investigations are necessary, especially on the basis of CT-based brachytherapy planning, to further improve the treatment results of multicatheter APBI.

Ott OJ, Schulz-Wendtland R, Uter W, Pfahlberg A, Beckmann MW, Sauer R, Strnad V. · Department of Radiation Oncology, University Hospital, Erlangen, Germany. · Strahlenther Onkol. · Pubmed #16220402 No free full text.

Abstract: PURPOSE: To investigate the incidence of fat necrosis, breast tissue fibrosis and breast pain after conserving surgery and accelerated partial-breast irradiation (APBI, group A), whole-breast external-beam irradiation (EBRT, group B), or EBRT combined with an interstitial boost (EBIB, group C) in women with breast cancer. PATIENTS AND METHODS: 85 patients who received breast-conserving therapy from 02/2000 to 03/2002 were analyzed. 30 patients received EBRT, 33 patients APBI, and 22 patients EBIB. Median follow-up was 35.5, 35.0, and 37.5 months, respectively. Fat necrosis was detected and rated by mammograms, fibrosis and pain were clinically rated with the LENT-SOMA scores. RESULTS: The incidence of fat necrosis was 15.3% for all patients; and 15.2%, 20.0%, and 9.0% for groups A, B, and C, respectively. The 3-year fat necrosis-free survival probability was 83%, 76%, and 95% (difference not significant). The mean time to first diagnosis of fat necrosis was 25.6, 26.2, and 26.0 months. No patient needed surgical intervention because of fat necrosis-related pain. Fibrosis was present in 27.3%, 63.3%, and 77.3% (p < 0.001), breast pain in 9.0%, 33.4%, and 18.1% (p < 0.05). CONCLUSION: Asymptomatic fat necrosis is a common finding after both percutaneous and interstitial irradiation after breast-conserving surgery. This analysis did not support the hypothesis that APBI with multicatheter implants leads to higher rates of fat necrosis, fibrosis, or pain.