Breast Neoplasms: Harms 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.

Harms W, Krempien R, Grehn C, Hensley F, Berns C, Wannenmacher M, Debus J. · Universität Heidelberg, Radiologische Klinik, Abteilung für Klinische Radiologie, INF 400, 69190 Heidelberg. · Zentralbl Gynakol. · Pubmed #14981565 No free full text.

Abstract: OBJECTIVE: The aim of this article was to describe the radio-therapeutic treatment options in previously irradiated patients suffering from breast cancer local recurrences and to review the literature. MATERIAL AND METHODS: Reirradiation of the chest wall can be performed using electron beams or alternatively CLDR/PDR (continuous/pulsed low dose rate) brachytherapy techniques with large skin moulds. With both techniques high doses can be applied to the chest wall while deeper-seated organs (lung, heart) can be spared to a large extent. Electron-beam therapy is readily available and the depth of treatment can be easily controlled by selecting the appropriate energy. The protracted irradiation schedule of CLDR/PDR brachytherapy results due to radiobiological reasons in a broad therapeutic ratio and safe treatment time. RESULTS: In the literature, more than 250 cases being reirradiated for chest wall local recurrences have been published. After retreatment using electron beams complete remissions were obtained in 41-74 % of the patients (brachytherapy 79-82 %). Severe grade IV complications (RTOG/EORTC) occurred in less than 10 % of the patients. CONCLUSIONS: With regard to the limited treatment options reirradiation of chest wall local recurrences resulted in high local control rates while toxicity remained acceptable. These data weaken the radio-therapeutic dogma that reirradiation of the chest wall may not be possible.

Thilmann C, Zabel A, Nill S, Rhein B, Hoess A, Haering P, Milke-Zabel S, Harms W, Schlegel W, Wannenmacher M, Debus J. · German Cancer Research Center, Heidelberg. · Med Dosim. · Pubmed #12074472 No free full text.

Abstract: Current methods for intensity-modulated radiotherapy (IMRT) in breast cancer use forward planning based on equivalent radiological path length to design intensity modulated tangential beams. Compared to conventional tangential techniques, dose reduction of organs at risk is limited using these techniques. We developed a method for intensity modulation of multiple beams for adjuvant radiotherapy of breast cancer by application of a virtual bolus defined on CT for inverse optimization. This method enables multibeam IMRT, which provides improved sparing of lung and heart tissue. In this paper, we present the general aspects of this approach and an evaluation of the optimum beam configuration for IMRT based on inverse treatment planning. We compared this method to conventional techniques. Different clinical examples illustrate the possible indications and feasibility of this new approach. This method is superior to conventional techniques because of the reduction of high-dose area of a substantial cardiac volume in those cases where the parasternal lymph nodes are part of the target volume.

Harms W, Becker HD, Krempien R, Wannenmacher M. · Department of Clinical Radiology, University of Heidelberg, Heidelberg, Germany. · Semin Surg Oncol. · Pubmed #11291133 No free full text.

Abstract: Sole brachytherapy for carcinoma of the lung is most often performed using high-dose-rate (HDR) remote afterloading equipment, which delivers the treatment within the tracheobronchial tree in an outpatient setting. It provides excellent, rapid palliation in advanced stages, and can also be used selectively for curative intent in early stages. In better-performance patients, fractionated external beam radiation therapy (EBRT) is preferred to brachytherapy as an initial treatment because it appears to provide a modest gain in survival, and more sustained palliation. In patients with centrally located tumors and limited extent of disease, the combination of external and endoluminal irradiation enables curative treatment options. Intraoperative brachytherapy may complement standard adjuvant treatment in incompletely resected, unresectable, or medically inoperable patients, and has the potential to improve local control in selected cases. Due to the rarity of the disease, the role of endoluminal brachytherapy in the treatment regimen of tracheal neoplasms is not yet clearly defined. The risk of fatal bleeding after endoluminal brachytherapy appears to be correlated with tumor localization and fraction size, but in the majority of cases fatal bleeds are caused by progression of local disease. The use of a distanceable applicator provides a central positioning of the source, prevents the delivery of high-contact doses to the mucosa, and may reduce toxicity. The standard technique for interstitial brachytherapy after breast-conserving surgery and adjuvant EBRT is the use of low-dose-rate (LDR) brachytherapy, but it may also be applied by means of pulsed-dose-rate (PDR) or HDR techniques. Prospective trials comparing different boost techniques and indications are needed to define more precisely the subgroup of patients who are most suitable for interstitial brachytherapy. Reirradiation of chest wall local recurrences using brachytherapy molds is effective and provides a high local control rate with acceptable toxicity.

Fritz P, Hensley FW, Berns C, Harms W, Wannenmacher M. · Department of Clinical Radiology, University of Heidelberg, Germany. · Strahlenther Onkol. · Pubmed #10987020 No free full text.

Abstract: PURPOSE: The concept of pulsed brachytherapy suggested by Brenner and Hall requires an unusual fractionation scheme. Effectiveness and sequelae of this new irradiation method were observed in patients with disseminated cutaneous metastases of breast cancer. PATIENTS AND METHODS: A flexible, reusable skin mold (weight 110 g) was developed for use with a pulsed dose rate (PDR) afterloader. An array of 18 parallel catheters (2 mm diameter) at equal distances of 10 or 12 mm was constructed by fixation of the catheters in a plastic wire mesh. The array is sewn between 2 foam rubber slabs of 5 mm thickness to provide a defined constant distance to the skin. Irradiations are possible up to a maximum field size of 20 x 23.5 cm using a nominal 37 GBq Ir-192 source. Pulses of 1 Gy reference dose at the skin surface are applied at a rate of 1 pulse every 1.2 hours (0.8 Gy per hour). The dose distribution is geometrically optimized to provide a homogeneous skin dose (100% +/- 10%). The 80% dose level lies at 5 mm below the skin surface. Between April 1994 and December 1997, 52 patients suffering from cutaneous metastases at the thoracic wall were treated with 54 fields and total doses of 38 to 50 Gy (median 42 Gy) applying 2 PDR courses with a pause of 4 to 5 weeks. RESULTS: Forty-six patients (48 fields) were eligible for evaluation in June 1998. The median follow-up was 16 months (range 7.1 to 46.2 months). Local control was achieved in 40 out of 48 fields (83%) or 41 of 46 patients (89%), respectively. Moist desquamation occurred in 52% of the patients. Late reactions were judged after a minimum follow-up of 6 months. Thirty-two fields had been previously irradiated with external beam therapy to doses of 40 to 60 Gy. Regardless of whether the skin was preirradiated or not all patients surviving long enough developed telangiectasia within 2 years after PDR irradiation. In preirradiated patients (n = 32) skin contractures and/or skin necrosis occurred in 12% each. In newly irradiated patients (n = 14) no contractures or skin necrosis were observed. CONCLUSIONS: Pulsed brachytherapy is an effective and time-sparing method for the treatment of cutaneous metastases from breast cancer. Skin reactions are comparable to the sequelae of orthovoltage therapy. Two sessions of approximately 20 Gy PDR were tolerated on preirradiated skin without severe sequelae.

Schöffel PJ, Harms W, Sroka-Perez G, Schlegel W, Karger CP. · German Cancer Research Center (DKFZ), Department of Medical Physics in Radiation Oncology, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. · Phys Med Biol. · Pubmed #17664587 No free full text.

Abstract: Accurate and reproducible patient setup is a prerequisite to fractionated radiotherapy. To evaluate the applicability and technical performance of a commercial 3D surface imaging system for repositioning of breast cancer patients, measurements were performed in a rigid anthropomorphic phantom as well as in healthy volunteers. The camera system records a respiration-gated surface model of the imaged object, which may be registered to a previously recorded reference model. A transformation is provided, which may be applied to the treatment couch to correct the setup of the patient. The system showed a high stability and detected pre-defined shifts of phantoms and healthy volunteers with an accuracy of 0.40 +/- 0.26 mm and 1.02 +/- 0.51 mm, respectively (spatial deviation between pre-defined shift and suggested correction). The accuracy of the suggested rotational correction around the vertical axis was always better than 0.3 degrees in phantom measurements and 0.8 degrees in volunteers, respectively. Comparison of the suggested setup correction with that detected by a second and independently operated marker-based optical system provided consistent results. The results demonstrate that the camera system provides highly accurate setup corrections in a phantom and healthy volunteers. The most efficient use of the system for improving the setup accuracy in breast cancer patients has to be investigated in routine patient treatments.

Eichbaum M, Harms W, Bolz S, Schneeweiss A, Sohn C. · Department of Gynecology and Obstetrics, University of Heidelberg Medical School, Heidelberg, Germany. · Onkologie. · Pubmed #17068387 No free full text.

Abstract: BACKGROUND: Lichen ruber planus is an inflammatory, pruritic disease of the skin and mucous membranes, which can be either generalized or localized. The etiology is unknown. PATIENTS AND METHODS: A 56-year-old female was treated with standard local radiotherapy after breast-conserving surgery due to high-grade ductal carcinoma in situ (DCIS) of the breast. RESULTS: During radiotherapy, the patient began to complain about increasing disseminated itching papules of the breast. The efflorescences appeared as flat-topped, solid, purplish papules spreading to the limbs and trunk. A thorough clinical examination revealed additionally suspicious cob-web like and white-coated mucosal lesions of the oral cavity consistent with the clinical diagnosis of a generalized lichen ruber planus with an oral manifestation. CONCLUSION: To our knowledge, this is the first report of a generalized manifestation of lichen ruber planus presumably induced by radiation therapy.

Harms W, Krempien R, Hensley FW, Berns C, Fritz P, Wannenmacher M. · Department of Clinical Radiology, Radiation Therapy, University of Heidelberg, Germany. · Strahlenther Onkol. · Pubmed #12426671 No free full text.

Abstract: PURPOSE: The aim of this study was to evaluate effect, toxicity, and cosmesis of a prospectively applied pulsed dose rate (PDR) brachytherapy boost schedule in patients with stage I/II/IIIa invasive breast cancer. PATIENTS AND METHODS: A total of 113 patients were treated after breast-conserving surgery (BCS) and external beam radiotherapy (median 50 Gy, range 46-52). The boost dose was graded in accordance to the pathologic tumor characteristics: 20-25 Gy: incomplete resection (n = 34), vascular invasion (n = 27), close margin resection (n = 41); 15 Gy: T2G3 stage (n = 11). PDR brachytherapy (37 GBq, (192)Ir source) was carried out after geometric volume optimization with 1 Gy/pulse/h. The implantation and dose specification were performed similar to the rules of the Paris system. RESULTS: The overall local failure rate after a median follow-up of 61 months was 4.4% (5/113). The actuarial 5- and 8-year local recurrence-free survival rates were 95% and 93%, respectively. Cosmesis was rated by 90% of the patients as excellent or good. 14/113 patients experienced grade III (all caused by planar telangiectasia) and none of the patients grade IV late toxicity of the skin (RTOG/EORTC). A boost dose of 25 Gy resulted in a significantly higher rate of late toxicity (Fisher's exact test, p < 0.01). CONCLUSIONS: PDR brachytherapy is safe, effective, and provides good cosmesis. A CLDR breast boost can be replaced by PDR brachytherapy without significant loss of therapeutic ratio.

Harms W, Krempien R, Hensley FW, Berns C, Wannenmacher M, Fritz P. · Department of Clinical Radiology, University of Heidelberg, Heidelberg, Germany. · Int J Radiat Oncol Biol Phys. · Pubmed #11163516 No free full text.

Abstract: PURPOSE: We report in a retrospective study on the effect and toxicity of chest wall reirradiation using pulsed-dose-rate (PDR) afterloading molds. METHODS AND MATERIALS: Between 1993 and 1999, a total of 58 patients were treated. All patients presented with locally recurrent breast cancer (31 patients had concomitant distant metastases) after mastectomy and a previously completed course of radiation therapy (median, 54 Gy; range, 36-70). Indication for reirradiation was a progressive macroscopic skin recurrence in 30 cases and an incomplete surgical resection in 28 patients. Standard treatment consisted of a split course with two fractions of 20 Gy (interval, 31 days). The reference dose was prescribed to the skin surface at 5 mm distance from the source. PDR brachytherapy (37 GBq, (192)Ir) was carried out after geometric distance optimization with 0.5-1 Gy/pulse/h. The irradiated median area was 423 cm(2) (range, 100-919). The median follow-up was 18 months (range, 7-84). RESULTS: The actuarial 1-, 2- and 3-year local recurrence-free survival rates in patients treated for macroscopic disease (microscopic disease in parenthesis) were 89% (96%), 81% (85%), and 75% (71%). Local control was obtained in 24/30 (22/28) patients. Twenty-nine of the 34 patients (85%) who deceased during follow-up were locally controlled. 9/58 patients experienced Grade III acute toxicity, 35/58 patients Grade III (29/58 telangiectasia, 6/58 contracture), and 4/58 Grade IV late toxicity (RTOG/EORTC). CONCLUSION: Reirradiation of the chest wall using PDR brachytherapy molds is effective and provides a high local control rate with acceptable toxicity.