Purpose: The aim of this review is to give an overview of the results of prospective and retrospective studies using allogenic reconstruction and postmastectomy radiotherapy (PMRT) in breast cancer and to make recommendations regarding this interdisciplinary approach. Materials and methods: A PubMed search was conducted to extract relevant articles from 2000 to 2024. The search was performed using the following terms: (breast cancer) AND (reconstruction OR implant OR expander) AND (radiotherapy OR radiation). Data from the literature on allogenic breast reconstruction and radiation are presented and discussed in relation to toxicity and cosmesis. Conclusion and recommendations: Breast reconstruction is also feasible if PMRT is necessary. Patients need to be informed about the relevant risk of capsular fibrosis and implant failure. A planned reconstruction is no reason to forgo PMRT nor is an indication for PMRT a reason to forego implant-based breast reconstruction if desired by the patient. It is important to provide detailed information here to enable shared decision-making. There is still no clear consensus regarding implant-based reconstruction (IBR) and PMRT. However, in clinical practice, both a one-stage (immediate “implant-direct” IBR) procedure with PMRT up to the final implant and a two-stage (immediate-delayed IBR) procedure with PMRT up to the tissue expander (TE) and later exchange of the TE are used; both approaches have their specific advantages and disadvantages. Depending on patient-specific factors and the surgeon’s experience and estimates, both IBR procedures are also possible in combination with PMRT. When using a TE/implant approach, completing skin stretching by adequately filling the expander before PMRT may be favorable. This approach is particularly practical when adjuvant chemotherapy is planned but may lead to postponement of radiotherapy when primary systemic therapy is given. According to the latest data, moderate hypofractionation also appears to be safe in the context of the IBR approach. It is important to have a closely coordinated interdisciplinary approach and to fully inform patients about the increased rate of potential side effects.

Background/Objectives: Definitive radiochemotherapy with concomitant cisplatin 40 mg/m² weekly represents the standard of care for locally advanced cervical cancer. Current studies (KEYNOTE-A18 and INTERLACE) are intensifying this regimen at the cost of increased hematologic toxicity. We aimed to evaluate influencing factors on hematotoxicity to ensure the safe application of radiochemotherapy. Methods: We retrospectively analyzed 147 patients, who received definitive radiochemotherapy between 2000 and 2019 and evaluated laboratory parameters before, after, and at each chemotherapy cycle to evaluate the occurrence, course, and profile of hematotoxicity. Further, we assessed the impact of hemoglobin levels and transfusion on oncological outcomes. Results: In a high-risk cervical cancer population with 82.3% of women with FIGO ≥ III stage, the 1-, 2-, and 5-year rates of overall survival (OS) were 89.1%, 74.7%, and 63.3%, and local control (LC) rates were 90.1%, 86.1%, and 75.0%, respectively. Grade 3 leukopenia was present in 2.1% and grade 3 anemia in 4.3%. No higher grade ≥ 4 hematotoxicity was observed. Absolute hemoglobin levels significantly reduced after the fourth cycle, with a median time from the start of therapy to hemoglobin nadir of 36 days. A lower hemoglobin nadir (<9 g/dL) was significantly associated with inferior LC. Red blood cell transfusion was applied in 44.9% of the women; the necessity of transfusion was significantly correlated to inferior OS, LC, and distant control. Conclusions: Our results suggest the need for special consideration of increased hematotoxicity and consistent implementation of anemia therapy, particularly from the fourth RT week onwards, to enable full-course definitive radiochemotherapy for locally advanced cervical cancer patients.

To use imaging data from stereotactic MR-guided online adaptive radiotherapy (SMART) of ultracentral lung tumors (ULT) for development of a safe non-adaptive approach towards stereotactic body radiotherapy (SBRT) of ULT. Analysis is based on 19 patients with ULT who received SMART (10 × 5.0–5.5 Gy) on a 0.35 T MR-Linac (MRIdian®) in the prospective MAGELLAN trial. 4D-planning CT data of six patients served to quantify proximal bronchial tree (PBT) breathing motion. Daily fraction MRIs are used to calculate interfractional translations (mediolateral (ML), anterior-posterior (AP), superior-inferior (SI)) and their dosimetric consequences for the PBT. A planning risk volume (PRV) is calculated for an assumed non-adaptive SBRT in deep-inspiration breath hold (DIBH) with surface-guidance (AlignRT®). Finally, non-adaptive volumetric modulated arc (VMAT) SBRT is simulated with and without a PRV for N = 10 patients (10 × 5.5 Gy). The PBT shows relevant breathing motion, especially in superior-inferior direction (median ML: 2.5 mm, AP: 1.9 mm and SI: 9.2 mm). Furthermore, moderate interfractional translations are observed (mean absolute translation ML: 1.3 mm, AP: 1.3 mm, SI: 1.1 mm), with an estimated 2 mm PRV margin for interfractional changes alone. Simulated non-adaptive SBRT leads to PBT overdoses in 60 % of patients (median overdosed fractions VMAT: 2.5, predicted MR-linac plans 4). Both MR-guided online plan adaptation (SMART) and PRV-based non-adaptive VMAT prevent PBT overdoses, but SMART yields significantly higher planning target volume (PTV) coverage (SMART: median 96 % [IQR 95–96], VMAT: median 89 % [IQR 77–94], p = 0.014). Both intrafractional breathing motion and interfractional translations may impact doses to the PBT during SBRT of ULT. SMART protects the PBT from overdoses while maintaining high PTV coverage. Non-adaptive SBRT appears safe with advanced breathing motion management and PRV, but yields inferior PTV coverage.

(1) Background: The management of ipsilateral breast cancer recurrence depends on the extent of the tumor, and staging results, and mastectomy is currently the standard of care for previously irradiated patients. Studies are increasingly investigating suitable candidates for the repeated use of breast-conserving approaches as an alternative to mastectomy. But this includes the crucial necessity for curative reirradiation (Re-RT). The therapeutic challenge in reirradiation involves finding a balance between tumor control and the risk of severe toxicity from cumulative radiation doses in previously irradiated organs. Re-RT options include the use of brachytherapy, intraoperative radiotherapy, or external beam RT with photons or electrons. The application of particle therapy using proton beam therapy represents an innovative radiotherapeutic technique for breast cancer patients that might offer advantageous physical properties, a superior dose reduction to adjacent organs-at-risk, and effective target volume coverage with lower integral doses to the patient’s whole body. In addition, this technique could potentially offer higher radiobiological effects and tumor responses. (2) Methods: The BREAST trial (NCT06954623) will be conducted as a prospective, single-arm, phase II study in 20 patients with histologically proven invasive breast cancer recurrences after repeat breast-conserving surgery and with an indication for local reirradiation. The patients will receive partial-breast re-RT with proton beam therapy in 15 once-daily fractions up to a total dose of 40.05 Gy(RBE), delivered with active raster scanning. The required time interval will be 1 year after previous RT to the ipsilateral breast. (3) Results: The following results will be reported: The primary endpoint is defined as the cumulative overall occurrence of (sub)acute skin toxicity of grade ≥ 3 within 6 months after the start of re-RT. Secondary outcome includes an analysis of the local, regional, and distant control, progression-free and overall survival, quality of life, and cosmesis. The explorative and translational objectives of this study include planning comparisons to other RT techniques and irradiation types, dosimetric evaluations, analyses of radiological imaging features, and translational assessments of cardiac toxicity biomarkers and tumor markers. (4) Conclusions: Overall, the aim of this study is to evaluate the potential of proton beam therapy for partial breast reirradiation and to establish the underlying data for a randomized trial.

Background/Objectives: Stereotactic body radiotherapy is frequently used in patients with adrenal metastases. Motion of adherent radiosensitive organs at risk (OARs) and tumors influence OAR toxicity and tumor control. Online-adaptive Magnetic Resonance-guided radiotherapy (MRgRT) can address and mitigate interfractional changes. However, the impact of intrafractional variations in adrenal MRgRT is unknown. Methods: A total of 23 patients with 24 adrenal metastases were treated with MRgRT. After daily plan adaptation and before beam application, an additional (preRT) 3d MRI was acquired. PreRT target volumes and OARs were retrospectively recontoured in 200 fractions. The delivered, online-adapted treatment plans, as well as non-adapted baseline plans, were calculated on these re-contoured structures to quantify the dosimetric impact of intrafractional variations on target volume coverage and OAR doses with and without online adaptation. Normal tissue complication probabilities (NTCPs) were calculated. Results: The median time between the two MRIs was 56.4 min. GTV and PTV coverage (dose to 95% of the PTV, D95%, and volume covered by 100% of the prescription dose, V100%) were significantly inferior in the preRT plans. GTV D_mean was significantly impaired in left-sided metastases, but not in right-sided metastases. Compared to non-adapted preRT plans, adapted preRT plans were still significantly superior for all GTV and PTV metrics. Intrafractional violations of OAR constraints were frequent. D0.5cc and the volume exposed to the near-maximum dose constraint were significantly higher in the preRT plans. The volume exposed to the D0.5cc constraints in single fractions escalated up to 1.5 cc for the esophagus, 3.2 cc for the stomach, 5.3 cc for the duodenum and 7.3 cc for the bowel. This led to significantly elevated NTCPs for the stomach, bowel and duodenum. Neither PTV D95%, nor gastrointestinal OAR maximum doses were significantly impaired by longer fraction duration. Conclusions: Intrafractional motion in adrenal MRgRT caused significant impairment of target volume coverage (D95% and V100%), potentially undermining local control. Frequent violation of gastrointestinal OAR constraints led to elevated NTCP. Compared to non-adaptive treatment, online adaptation still highly improved GTV and PTV coverage.