Breast Neoplasms: Budach W

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.

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.

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.

Hehr T, Lamprecht U, Glocker S, Classen J, Paulsen F, Budach W, Bamberg M. · Department of Radiation Oncology, Eberhard-Karls-University of Tübingen, Germany. · Int J Hyperthermia. · Pubmed #11471981 No free full text.

Abstract: PURPOSE: This retrospective analysis investigated the effectiveness and side-effects of combined hyperthermia and radiation therapy in locally recurrent breast cancer after primary modified radical mastectomy. The aim of the thermoradiotherapy was to reduce the substantial risk of symptomatic chest wall disease. MATERIALS AND METHODS: Between May 1995-August 1998, 39 extensively pre-treated women with progressive locoregional chest wall tumours were treated with local radiofrequency hyperthermia, given twice a week immediately before radiotherapy. Sixty-two per cent of the patients had received previous radiotherapy, with a median dose of 50 Gy, 64% had received chemotherapy, 36% hormonal therapy, and 13% local therapy with miltefosin, respectively. Nine patients were treated for microscopic residual disease after local tumour excision (R1-resection) and 30 patients for gross macroscopic nodular recurrences. Twenty-seven patients had two adjacent hyperthermia fields at the ipsilateral chest wall to cover the whole irradiation area. Each field received a median of seven local hyperthermia sessions (range 2-12, average 5.6 sessions) just before radiation therapy, with a median dose of 60 Gy (range 30-68 Gy). The monitored maximum(average) and average(average) epicutaneous temperatures were 42.1 degrees C and 41.0 degrees C, respectively. Maximum(average) and average(average) intratumoural temperatures of 43.0 degrees C and 41.1 degrees C, respectively, were achieved in nine chest wall recurrences with intratumoural temperature probes. Concurrent hormonal therapy was administered in 48%, and concurrent chemotherapy in 10% of patients. RESULTS: Median overall survival time was 28 months (Kaplan Meier), with 71% and 54% of patients living 1 and 2 years after thermoradiotherapy. The median time to local failure has not been reached, local tumour control after 2 years being 53%. Actuarial 1 and 2 year local tumour controls for microscopic residual disease were 89%, and for macroscopic nodular recurrences 71% and 46%, respectively (p = 0.09). Actuarial 1 and 2 year local tumour controls after treatment with a total dose of less than 60 Gy were 51% and 38%, respectively, and, after a total dose greater than 60 Gy, 84% and 60% (p = 0.01), respectively. Actuarial 1 year local tumour control was 92% after complete tumour remission, versus 57% after partial remission (p = 0.002). Three of the 39 patients died of cancer en cuirasse, 13 patients due to distant metastases. Acute thermoradiotherapy related erythema, dry desquamation and moist desquamation were seen in 28.2%, 30.7%, and 30.7% of patients, respectively. Soft tissue necrosis occurred in two patients with previous post-operative delayed wound healing, and in one patient above a silicon implant. CONCLUSION: This study showed that, in extensively pre-treated patients with locally recurrent breast cancer, local tumour control after thermoradiotherapy depended on tumour resectability, response of macroscopic tumour to thermoradiotherapy, and total irradiation dose.

Budach W. · Department of Radiation Oncology, University of Düsseldorf, Germany. · Strahlenther Onkol. · Pubmed #18166997 No free full text.

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Bölke E, Peiper M, Budach W, Matuschek C, Schwarz A, Orth K, Gripp S. · Department of Radiation Therapy and Radiation Oncology, University of Düsseldorf, Germany. · Eur J Med Res. · Pubmed #17933706 No free full text.

Abstract: BACKGROUND: Keloid is a hypertrophic scar that may arise within 6 months after injury in susceptible individuals. Different therapies like surgical excision, intralesional steroid injections, local application of pressure, or postoperative irradiation with x-rays or electrons are reported. Although an immediate starting of therapy after surgery is usually recommended, delayed radiotherapy may also be effective. CASE REPORT: We report on a 48 year old women with a history of an invasive ductal carcinoma in the upper lateral quadrant of the left breast. A breast conserving tumor resection with axillary dissection was performed. An adapting reduction mammaplasty was carried out on the right breast for cosmetic reasons at the same time. 5 weeks after surgery, adjuvant radiotherapy was applied with a total dose of 59 Gy to the left breast. 10 weeks after surgery and by the end of radiotherapy, a keloid had developed on the right breast with reduction mammaplasty, but not on the left irradiated one. 8 months after initial surgery the patient's keloid formation on the right mamma was removed by surgical resection and a keloid prevention with postoperative radiotherapy with 20 Gy was performed. CONCLUSION: Postoperative radiation of the scar prevented effectively keloid formation while simultaneously a hypertrophic scar developed in the non-irradiated scar.

Gripp S, Moeller S, Bölke E, Schmitt G, Matuschek C, Asgari S, Asgharzadeh F, Roth S, Budach W, Franz M, Willers R. · Department of Radiation Oncology, University Hospital Düsseldorf at Heinrich-Heine-University, Düsseldorf, Germany. · J Clin Oncol. · Pubmed #17664480 No free full text.

Abstract: PURPOSE: To study how survival of palliative cancer patients relates to subjective prediction of survival, objective prognostic factors (PFs), and individual psychological coping. PATIENTS AND METHODS: Survival was estimated according to three categories (< 1 month, 1 to 6 months, and > 6 months) by two physicians (A and B) and the institutional tumor board (C) for 216 patients recently referred for palliative radiotherapy. After 6 months, the accuracy of these estimates was assessed. The prognostic relevance of clinical symptoms, performance status, laboratory tests, and self-reported emotional distress (Hospital Anxiety and Depression Scale) was investigated. RESULTS: In 61%, 55%, and 63% of the patients, prognoses were correctly estimated by A, B, and C, respectively. kappa statistic showed fair agreement of the estimates, which proved to be overly optimistic. Accuracy of the three estimates did not improve with increasing professional experience. In particular, the survival of 96%, 71%, and 87% of patients who died in less than 1 month was overestimated by A, B, and C, respectively. On univariate analysis, 11 of 27 parameters significantly affected survival, namely performance status, primary cancer, fatigue, dyspnea, use of strong analgesics, brain metastases, leukocytosis, lactate dehydrogenase (LDH), depression, and anxiety. On multivariate analysis, colorectal and breast cancer had a favorable prognosis, whereas brain metastases, Karnofsky performance status less than 50%, strong analgesics, dyspnea, LDH, and leukocytosis were associated with a poor prognosis. CONCLUSION: This study revealed that physicians' survival estimates were unreliable, especially in the case of patients near death. Self-reported emotional distress and objective PFs may improve the accuracy of survival estimates.

Welz S, Hehr T, Lamprecht U, Scheithauer H, Budach W, Bamberg M. · Department of Radiation Oncology, Eberhard-Karls-Universität Tübingen, Hoppe-Seyler-Str. 3, 72076 Tübingen, Germany. · Int J Hyperthermia. · Pubmed #15764357 No free full text.

Abstract: BACKGROUND AND PURPOSE: Evaluation of the efficacy of combined hyperthermia and radiotherapy (TRT) in high-risk breast cancer patients with microscopic involved margins (R1) after mastectomy or with resected locoregional, early recurrence with close margins or R1-resection. Main endpoint was local tumour control (LC); secondary endpoints were overall survival (OS), disease free survival (DFS) and acute toxicity. MATERIAL AND METHODS: Between 1997-2001, 50 patients were treated with TRT. Thirteen patients (group 1) received a post-operative TRT in a high-risk situation (free margin <1 cm or R1, N+), 37 patients (group 2) received TRT after close/R1 resection of a locoregional recurrence. Thirteen out of 37 patients in group 2 already had had two-to-seven recurrences prior to TRT. Median radiation dose was 60 Gy (range: 44-66.4 Gy), the additional local hyperthermia (>41 degrees C, 60 min) was given twice a week. Median follow-up for patients at risk was 28 months. All statistical tests were done using Statistica software. RESULTS: Actuarial OS for all patients at 3 years accounted for 89%, DFS for 68% and LC for 80%. Actuarial OS was 90% for group 1 and 89% for group 2, with four patients having died so far. DFS at 3 years was 64% in group 1 and 69% in group 2, actuarial 3 year LC was 75% and 81%, respectively. For patients with recurrent chest wall disease, there was no difference concerning local control between patients who underwent TRT with or without prior radiation. No prognostic factors could be detected due to the small number of patients investigated. The combined modality treatment was well tolerated. Grade IV toxicity, according to the Common Toxicity Criteria, did not occur. CONCLUSION: The results concerning local tumour control and overall survival in these high-risk patients are promising, especially for TRT for the treatment of local recurrences. A longer follow-up is needed to estimate late toxicity.

Marini P, Schmid A, Jendrossek V, Faltin H, Daniel PT, Budach W, Belka C. · Department of Radiation Oncology, University of Tübingen, Experimental Radiation Oncology, Hoppe-Seyler-Str, 3, D-72076 Tübingen, Germany. · BMC Cancer. · Pubmed #15651986 links to  free full text

Abstract: BACKGROUND: TRAIL (tumor necrosis factor related apoptosis inducing ligand) is an apoptosis inducing ligand with high specificity for malignant cell systems. Combined treatment modalities using TRAIL and cytotoxic drugs revealed highly additive effects in different tumour cell lines. Little is known about the efficacy and underlying mechanistic effects of a combined therapy using TRAIL and ionising radiation in solid tumour cell systems. Additionally, little is known about the effect of TRAIL combined with radiation on normal tissues. METHODS: Tumour cell systems derived from breast- (MDA MB231), lung--(NCI H460) colorectal--(Colo 205, HCT-15) and head and neck cancer (FaDu, SCC-4) were treated with a combination of TRAIL and irradiation using two different time schedules. Normal tissue cultures from breast, prostate, renal and bronchial epithelia, small muscle cells, endothelial cells, hepatocytes and fibroblasts were tested accordingly. Apoptosis was determined by fluorescence microscopy and western blot determination of PARP processing. Upregulation of death receptors was quantified by flow cytometry. RESULTS: The combined treatment of TRAIL with irradiation strongly increased apoptosis induction in all treated tumour cell lines compared to treatment with TRAIL or irradiation alone. The synergistic effect was most prominent after sequential application of TRAIL after irradiation. Upregulation of TRAIL receptor DR5 after irradiation was observed in four of six tumour cell lines but did not correlate to tumour cell sensitisation to TRAIL. TRAIL did not show toxicity in normal tissue cell systems. In addition, pre-irradiation did not sensitise all nine tested human normal tissue cell cultures to TRAIL. CONCLUSIONS: Based on the in vitro data, TRAIL represents a very promising candidate for combination with radiotherapy. Sequential application of ionising radiation followed by TRAIL is associated with an synergistic induction of cell death in a large panel of solid tumour cell lines. However, TRAIL receptor upregulation may not be the sole mechanism by which sensitation to TRAIL after irradiation is induced.

Hehr T, Classen J, Huth M, Durst I, Christ G, Bamberg M, Budach W. · Department of Radiation Oncology, University of Tuebingen, Tuebingen, Germany. · Strahlenther Onkol. · Pubmed #15480511 No free full text.

Abstract: BACKGROUND AND PURPOSE: Different radiotherapy techniques are being used for postmastectomy irradiation. A retrospective analysis of patterns of locoregional failure (LRF) after modified radical mastectomy and axillary lymph node dissection followed by locoregional radiotherapy with or without systemic treatment was performed. Main emphasis was focused on the comparison of two postmastectomy radiotherapy techniques. PATIENTS AND METHODS: 287 evaluable patients with locally advanced disease and/or adverse pathologic features (pT3 17% of patients, pT4 35%, multicentricity 25%, pN more than three positive nodes and/or pN1biii 70%, "close margins" 29%, infiltration of pectoral fascia 20%) with or without adjuvant chemo-hormonal treatment were included between 1989 and 2000. Median age was 61 years (range 24-88 years). All patients had modified radical mastectomy and axillary lymphonodectomy level I-II(III) for primary breast cancer. Median total dose of conventionally fractionated radiotherapy to the chest wall was 50 Gy (range 46-56 Gy). A local boost to the tumor bed of 10 Gy was applied in 72 patients. 80% of the patients received supraclavicular and 60% ipsilateral internal mammary lymph node irradiation of 50 Gy. 19% of the patients received adjuvant chemo-hormonal therapy, 38% hormonal therapy, and 27% chemotherapy. The median follow-up of patients at risk was 43 months (average 54 months). RESULTS: The 5-year locoregional tumor control (LRC), LRC first event, disease-free, and overall survival were 85%, 91%, 61%, and 70% (Kaplan-Meier analysis), respectively. Cox regression analysis showed that stage III (relative risk [RR] 1.7), more than three involved axillary lymph nodes (RR 5.1), and infiltration of the pectoral fascia (RR 3.2) increased the risk of locoregional failure, while positive estrogen receptor status (RR 0.3) was associated with a reduced risk. No statistically significant differences in LRC were observed for patients treated either with the electron-rotation technique (LRC 92%) or with the photon-based technique (LRC 89%; p = 0.9). A subgroup analysis of tumors resected with "close margins" showed a higher LRF rate of 25% after electronbeam-rotation irradiation (n = 180) compared to an LRF of 13% with tangential opposed 6-MV photon fields (n = 107; p < 0.05). Large primary tumors of > or = 5 cm developed LRF in 29% of patients treated with electron-beam-rotation irradiation and in 17% of patients with photon-based irradiation (p = 0.1). CONCLUSION: In locally advanced breast cancer, the LRC after postmastectomy irradiation with both techniques is comparable with published data from randomized studies. The tangential opposed photon field technique seems to be beneficial after marginal resection (histopathologic "close margins") of the primary tumor.

Hehr T, Budach W, Durst I, Glocker S, Classen J, Weinmann M, Christ G, Bamberg M. · Department of Radiation Oncology, University of Tuebingen, Germany. · Strahlenther Onkol. · Pubmed #12426673 No free full text.

Abstract: BACKGROUND: Different radiotherapy techniques are used for postmastectomy irradiation. We review the results with the electron-beam-rotation technique in advanced breast cancer patients. Main endpoint was local tumor control. PATIENTS AND METHODS: From 1990 to 1998 119 patients with adverse pathology features (pT3 17% of patients, pT4 42%, multicentricity 36%, pN >/= 3 positive nodes and/or pN1biii 81%, close margins 30%) underwent electron-beam-rotation irradiation of the chest wall with daily fractions of 2.0-2.5 Gy per day to 50 Gy total dose after modified radical mastectomy and axillary lymph node dissection. A local boost of 10 Gy and/or irradiation of locoregional lymph nodes were applied depending on the completeness of resection and lymph node involvement. RESULTS: After a median follow-up of 73 months for patients at risk the 5-year local tumor control, local tumor control first event, disease-free, and overall survival were 82%, 92%, 57%, and 63% (Kaplen Meier analysis), respectively. Significant predictors of poor local tumor control were maximal tumor diameter >/= 5 cm (p = 0.01), "close margins" or residual tumor (p < 0.01), four or more involved axillary lymph nodes (p = 0.02), two or more involved lymph node levels (p = 0.04), negative estrogen receptor status (p = 0.03), and high-grade histopathology (GIIb-III, p < 0.01). The subgroup analysis showed a high local failure rate of 37% for high-grade (GIIb-III) and estrogen receptor negative tumors, whereas no local recurrence was found in low-grade (GI-Iia) and receptor positive tumors (p = 0.01). The multivariate analysis revealed maximal tumor diameter >/= 5 cm, four or more involved axillary lymph nodes and high-grade histopathology (GIIb-III) as independent predictors of poor local tumor control. CONCLUSION: In high-risk breast cancer patients postmastectomy irradiation with the electron-beam-rotation technique is an effective therapy, resulting in a 5-year local failure rate of 8%. Intensified local therapy needs further investigation in subgroups of patients with additional risk factors.

Paulsen F, Belka C, Gromoll C, Hehr T, Friedel G, Wolf H, Budach W, Bamberg M. · Department of Radiotherapy, University of Tübingen, Germany. · Int J Hyperthermia. · Pubmed #10949128 No free full text.

Abstract: This paper reports on a woman with a rapidly growing recurrent cystosarcoma phyllodes malignum after two major attempts of surgery. In this situation, neoadjuvant hyperfractionated radiotherapy, superficial hyperthermia and ifosfamide were administered. Toxicity was mild. Resection of the tumour bed revealed a pathologically complete response with an actual disease free follow-up of 48 months.

Hehr T, Budach W, Paulsen F, Gromoll C, Christ G, Bamberg M. · Department of Radiotherapy and Oncology, CRONA, Tübingen, Germany. · Radiother Oncol. · Pubmed #10392814 No free full text.

Abstract: BACKGROUND AND PURPOSE: Different radiotherapy techniques are being used for chest wall irradiation after mastectomy. We review our results with the electron-beam-rotation technique in a series of 130 high risk breast cancer patients. The main end point of the study was local tumour control; secondary end points were disease free survival, and overall survival, as well as acute and late side effects. MATERIAL AND METHODS: From January 1990 to June 1995, 89 patients underwent electron-beam-rotation irradiation of the chest wall after primary mastectomy and axillary lymph node dissection (group I) and 41 patients after excision of local recurrent breast cancer (group II) with 4 x 2.5 Gy/week to 50 Gy total dose (4-12 MeV electrons depending on the thickness of the chest wall). In addition, irradiation of local-regional lymph nodes and/or a local boost of 10 Gy were applied dependent on the resection and node status. RESULTS: After a median follow up of 29 months (65% stadium III/IV) the 3 year local tumour control, disease free survival, and overall survival were 73%, 47%, and 75%, respectively. Local control in group I was 78% versus 60% in group II. Significant predictors for local tumour control, disease free survival, and overall survival were resection status (R0 versus R1/2) and estrogen receptor status (positive versus negative). In group I, tumour grading (GI-IIa versus GIIb-III) and estrogen receptor status were found to be additional significant prognostic factors for complete resected tumours. Five patients developed symptomatic pneumonitis (< 4%) and one patient developed a chronic fistula at the resection. A significant correlation between the degree of acute skin reaction and persistent pigmentation was observed. CONCLUSION: In high risk breast cancer patients postoperative irradiation with the electron-beam-rotation technique of the chest wall is an effective therapy resulting in 78% local tumour control at 3 years for locally advanced breast cancer and 60% for recurrent disease. The rate of acute and late toxicity is low. The degree of acute skin reaction correlates with the degree of persistent pigmentation.

Bölke E, Matuschek C, Gripp S, Budach W, Gerber PA, Peiper M. · No affiliation provided · J Clin Oncol. · Pubmed #18854555 No free full text.

This publication has no abstract.