The impact of fractionation on secondary malignancies in postoperative breast cancer irradiation.

PURPOSE: Randomized studies demonstrated the oncological equivalence of (ultra-)hypofractionation compared to a 5-week schedule in postoperative radiotherapy of breast cancer. Due to the low incidence and long latency of secondary malignancies, there are currently no reliable clinical data regarding the influence of fractionation regimens on the development of secondary malignancies. MATERIAL AND METHODS: For 20 patients with right or left-sided breast cancer, postoperative treatment plans were created using 3D-CRT (n = 10) or VMAT (n = 10) for three different fractionation schedules: 5-week schedule with 50.4Gy in 1.8Gy (28fx), hypofractionation with 40.05Gy in 2.67Gy (15fx) and ultra-hypofractionation with 26Gy in 5.2Gy (5fx). The EARs (absolute additional cases of disease per 10,000 patient-years) for secondary malignancies in the lung, contralateral breast, esophagus, liver, thyroid, spinal cord, bones and soft tissue were calculated using a fraction-dependent dose-response model. RESULTS: Based on risk modulation, (ultra-)hypofractionation resulted in significantly lower EARs for lung cancer (LC), contralateral breast cancer (CBC) and soft tissue sarcoma (STS) (p < .001). For the ultra-hypofractionated dose concept the median EARs for LC, CBC and STS were 42.8 %, 39.4 % and 58.1 % lower compared to conventional fractionation and 31.2 %, 25.7 % and 20.3 % compared to hypofractionation. The influence of fractionation on the risk of secondary malignancies for LC and CBC was less pronounced with 3D-CRT than with VMAT. For STS, however, the influence of fractionation was greater with 3D-CRT than with VMAT. CONCLUSION: Based on this simulation study (ultra-)hypofractionated postoperative breast cancer irradiation may be associated with a lower risk of secondary malignancies compared to a 5-week schedule.

Incidental dose distribution to contralateral internal mammary nodes in breast cancer patients undergoing adjuvant radiotherapy.

Background and purpose: In a relevant number of primary breast cancer patients, lymphatic drainage to the contralateral internal mammary nodes (cIMN) is being observed. Nevertheless, so far lymphatic drainage pathway to the cIMN is largely neglected during adjuvant radiotherapy. Materials and methods: This study evaluated the incidental dose to the cIMN for 120 volumetric modulated arc therapy (VMAT) treatment plans for node positive breast in dependence of internal mammary node irradiation (IMNI) and deep inspiration breath hold (DIBH). Additionally, incidental dose distribution to the cIMN based on the field design in the MA20, EORTC22922/10925 and AMAROS trials was assessed. Results: The incidental dose (Dmean ± SD) to the cIMN-CTV was 13.0 (±4.7) Gy with a maximum dose of < 30 Gy in 113/120 cases. If IMNI was included (n = 80), the Dmean to the cIMN-CTV was significantly higher compared to no IMNI, but still comparably low (n = 40; 14.3 Gy vs. 9.6 Gy; p = 0.0001). Furthermore, the dose in the cIMN during free breathing (n = 80) was higher compared to DIBH (n = 40; 13.9 Gy vs. 11.2 Gy; p = 0.002).Simulated treatment plans based on the randomized RNI trials revealed neglectable dose coverage of the cIMN (Dmean 1.0-1.8 Gy) for all protocols. Conclusion: Neither in the randomized RNI trials nor during contemporary treatment techniques clinically relevant dose distribution to the cIMN was observed. Further studies are warranted to assess the potential impact of intended irradiation of cIMN in high-risk patients.

A survey of cancer patients' interest in undertaking exercise to promote relaxation during radiotherapy for breast cancer and metastatic cancer.

BACKGROUND: Approximately 25-50% of patients undergoing radiotherapy (RT) experience psychological distress and anxiety, which can detrimentally affect both their quality of life and treatment outcomes. While previous research has demonstrated that relaxation exercises can enhance the tolerability of RT and alleviate associated stress and anxiety, the specific needs for such therapies in radiation oncology remain under-explored. This study aims to investigate the demand for and preferences toward relaxation exercises among radiotherapy patients, addressing a critical gap in patient-centered care. METHODS: A prospective pseudonymized survey study using a one-time paper-based questionnaire was conducted from 2022 to 2023 among patients undergoing curative-intent RT for breast cancer or patients undergoing palliative RT for bone metastases. Patients were asked in a 11-item questionnaire about their anxiety, pre-existing practice of relaxation exercises/interventions, their interest in relaxation exercises, and preferences on the type and format of instruction. Data were analyzed descriptively. RESULTS: 100 patients (74 female and 26 male) responded, of whom 68 received curative-intent adjuvant RT and 32 palliative RT. Median age was 62 years. 78% of patients indicated a desire to be actively involved in their radiotherapy, but only 27% had used relaxation exercises prior to RT. 44.8% of both curatively and palliatively treated patients who wanted to be actively involved in their therapy desired to learn how to best relax. 56.4% of respondents were willing to spend extra time learning offered exercises. CONCLUSION: The survey indicates that patients undergoing RT, both for curative or palliative intent, desire relaxation exercises to relieve stress and anxiety from RT. It is therefore important to assess the need for relaxation interventions in individual patients and to develop suitable programs or collaborate with other healthcare professionals to meet these needs.

Detecting Metastatic Patterns of Oligometastatic Breast Cancer: A Comparative Analysis of 18F-FDG PET/CT and Conventional CT Imaging.

Metastasis-directed therapy has the potential to improve progression-free and overall survival in oligometastatic disease (OMD). For breast cancer, however, randomized trials have failed so far to confirm this finding. Because the concept of metastasis-directed therapy in OMD is highly dependent on the accuracy of the imaging modality, we aimed to assess the impact of 18F-FDG PET/CT on the definition of OMD in breast cancer patients. Methods: Eighty patients with a total of 150 18F-FDG PET/CT images (between October 2006 and January 2022) were enrolled in this retrospective study at the Technical University of Munich. The inclusion criteria were OMD, defined as 1-5 distant metastases, at the time of 18F-FDG PET/CT. For the current study, we systemically compared the metastatic pattern on 18F-FDG PET/CT with conventional CT. Results: At the time of 18F-FDG PET/CT, 21.3% of patients (n = 32) had a first-time diagnosis of metastatic disease, 40.7% (n = 61) had a previous history of OMD, and 38% (n = 57) had a previous history of polymetastatic disease. In 45.3% of cases, the imaging modality (18F-FDG PET/CT vs. conventional CT) had an impact on the assessment of whether OMD was present. An identical metastatic pattern was observed in only 32% of cases.18F-FDG PET/CT detected additional metastases in 33.3% of cases, mostly in the nonregional lymph node system. Conclusion: The use of 18F-FDG PET/CT had a substantial impact on the definition of OMD and detection of metastatic pattern in breast cancer. Our results emphasize the importance of establishing a standardized definition for imaging modalities in future trials and clinical practices related to metastasis-directed therapy in breast cancer patients.

DEGRO guideline for personalized radiotherapy of brain metastases and leptomeningeal carcinomatosis in patients with breast cancer.

PURPOSE: The aim of this review was to evaluate the existing evidence for radiotherapy for brain metastases in breast cancer patients and provide recommendations for the use of radiotherapy for brain metastases and leptomeningeal carcinomatosis. MATERIALS AND METHODS: For the current review, a PubMed search was conducted including articles from 01/1985 to 05/2023. The search was performed using the following terms: (brain metastases OR leptomeningeal carcinomatosis) AND (breast cancer OR breast) AND (radiotherapy OR ablative radiotherapy OR radiosurgery OR stereotactic OR radiation). CONCLUSION AND RECOMMENDATIONS: Despite the fact that the biological subtype of breast cancer influences both the occurrence and relapse patterns of breast cancer brain metastases (BCBM), for most scenarios, no specific recommendations regarding radiotherapy can be made based on the existing evidence. For a limited number of BCBM (1-4), stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT) is generally recommended irrespective of molecular subtype and concurrent/planned systemic therapy. In patients with 5-10 oligo-brain metastases, these techniques can also be conditionally recommended. For multiple, especially symptomatic BCBM, whole-brain radiotherapy (WBRT), if possible with hippocampal sparing, is recommended. In cases of multiple asymptomatic BCBM (≥ 5), if SRS/SRT is not feasible or in disseminated brain metastases (> 10), postponing WBRT with early reassessment and reevaluation of local treatment options (8-12 weeks) may be discussed if a HER2/Neu-targeting systemic therapy with significant response rates in the central nervous system (CNS) is being used. In symptomatic leptomeningeal carcinomatosis, local radiotherapy (WBRT or local spinal irradiation) should be performed in addition to systemic therapy. In patients with disseminated leptomeningeal carcinomatosis in good clinical condition and with only limited or stable extra-CNS disease, craniospinal irradiation (CSI) may be considered. Data regarding the toxicity of combining systemic therapies with cranial and spinal radiotherapy are sparse. Therefore, no clear recommendations can be given, and each case should be discussed individually in an interdisciplinary setting.

Tumor Contact With Internal Mammary Perforator Vessels as Risk Factor for Gross Internal Mammary Lymph Node Involvement in Patients With Breast Cancer.

PURPOSE: The identification of internal mammary lymph node metastases and the assessment of associated risk factors are crucial for adjuvant regional lymph node irradiation in patients with breast cancer. The current study aims to investigate whether tumor contact with internal mammary perforator vessels is associated with gross internal mammary lymph node involvement. METHODS AND MATERIALS: We included 297 patients with primary breast cancer and gross internal mammary (IMN+) and/or axillary metastases as well as 230 patients without lymph node metastases. Based on pretreatment dynamic contrast-enhanced magnetic resonance imaging, we assessed contact of the tumor with the internal mammary perforating vessels (IMPV). RESULTS: A total of 59 patients had ipsilateral IMN+ (iIMN+), 10 patients had contralateral IMN+ (cIMN+), and 228 patients had ipsilateral axillary metastases without IMN; 230 patients had node-negative breast cancer. In patients with iIMN+, 100% of tumors had contact with ipsilateral IMPV, with 94.9% (n = 56) classified as major contact. In iIMN- patients, major IMPV contact was observed in only 25.3% (n = 116), and 36.2% (n = 166) had no IMPV contact at all. Receiver operating characteristic analysis revealed that "major IMPV contact" was more accurate in predicting iIMN+ (area under the curve, 0.85) compared with a multivariate model combining grade of differentiation, tumor site, size, and molecular subtype (area under the curve, 0.65). Strikingly, among patients with cIMN+, 100% of tumors had contact with a crossing contralateral IMPV, whereas in cIMN- patients, IMPVs to the contralateral side were observed in only 53.4% (iIMN+) and 24.8% (iIMN-), respectively. CONCLUSIONS: Tumor contact with the IMPV is highly associated with risk of gross IMN involvement. Further studies are warranted to investigate whether this identified risk factor is also associated with microscopic IMN involvement and whether it can assist in the selection of patients with breast cancer for irradiation of the internal mammary lymph nodes.