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Purpose: To assess the impact of interfractional variations of shape and setup uncertainties on the dose to the parotid glands (PGs) in head-and-neck cancer intensity-modulated radiotherapy and image-guided radiotherapy (IGRT). Methods and Materials: Two scenarios were analyzed retrospectively for 10 head-and-neck cancer patients, treated with helical TomoTherapy (TomoTherapy Inc., Madison, WI): the IGRT scenario and the non-IGRT scenario. The initial dose-volume histograms derived from the planning computed tomography (PCT) scan and 120 recalculated dose-volume histograms of the PGs of each scenario and of corresponding fractions were compared. Setup errors, cumulative median doses (CMDs) for 6 fractions, overall volumes of the PGs, and volumes that received less than 1 Gy or more than 1.6 Gy per fraction were analyzed. Results: The mean decrease in the PG volume was 0.13 cm(3)/d. There was a significantly higher CMD than initially predicted (mean increase for 6 fractions, 1.13 Gy for IGRT and 0.96 Gy for non-IGRT). The volume that received less than 1 Gy per fraction decreased (mean difference to PCT, 1.36 cm(3) for IGRT [p = 0.003] and 1.35 cm(3) for non-IGRT [p = 0.003]) and the volume that received more than 1.6 Gy per fraction increased with increasing fraction number (mean difference to PCT, 1.14 cm(3) for IGRT [p = 0.01] and 1.16 cm(3) for non-IGRT [p = 0.006]). There was no statistically significant difference between the two scenarios (CMD, p = 0.095; volume that received <1 Gy per fraction, p = 0.896; and volume that received >1.6 Gy per fraction, p = 0.855). Conclusions: In the analyzed group the actual delivered dose to the PGs does not differ significantly between an IGRT and a non-IGRT approach. However, IGRT in head-and-neck cancer intensity-modulated radiotherapy is strongly recommended to improve patient setup. [ABSTRACT FROM AUTHOR]

Total neoadjuvant therapy (TNT) of rectal cancer improves rates of pathological complete remission and progression-free survival. With improved clinical response rates, interest grew in a non-operative approach/watch and wait (WaW) for this disease. In 2020, the working groups of ACO/AIO/ARO published a consensus statement on the use of TNT, including a non-operative approach. However, the best combination scheme remains unclear. Despite the increasing use of TNT, there is a lack of comprehensive data on its current implementation and practices. To address this knowledge gap, a multicenter survey was conducted to capture the use of TNT protocols in German-speaking radiotherapy departments. At the beginning of 2023, a GDPR-compliant online survey was conducted in Germany, Austria, and German-speaking Switzerland. The questionnaire comprised 43 questions covering various aspects of TNT, including chemotherapy and WaW concepts. Most respondents (98.4%) confirmed awareness of the consensus on TNT for rectal cancer. Institutions treated an average of 30.22 rectal cancer patients annually. Most respondents (76.2%) reported treating over 80% of patients neoadjuvantly. Regarding TNT, 33.3% treated 21-50% with such a protocol. No significant association was found between the institution type and TNT application. In 62/63 cases, tumor board discussion was standard before offering TNT. VMAT was the predominant technique (82.5%). For rectal cancer dosing, the 50/50.4Gy scheme was most common, followed by 45Gy with a boost and the 5 × 5Gy scheme. Dosing schemes for TNT varied slightly, with more participants reporting the use of 5 × 5Gy compared to radiation therapy for rectal cancer in general. CBCT was the primary IGRT method (88.9%). Larger hospitals typically administered chemotherapy themselves, while private practices collaborated with medical oncologists (p < 0.0001). The most common concurrent chemotherapy drugs were 5-fluorouracil/capecitabine (64.4%) and oxaliplatin (37.3%). A WaW strategy was reported to be institutional implemented by 63.8%. The timing of offering WaW was split, with 50% offering it after radiochemotherapy and 47% during the informed consent talk. For planned WaW, 62% prefer normofractionated TNT. TNT appears to be widely implemented in the German-speaking radio-oncological community, regardless of the type of institution. Image-guided therapy, multidisciplinary team decisions, and internal guidelines play an important role. TNT seems to have already altered treatment protocols for rectal cancer toward an organ-preserving approach in selected cases. In these WaW cases, normofractionation appears to be preferred over hypofractionation., (© 2024. The Author(s).)

Skin inflammation with the potential sequel of moist epitheliolysis and edema constitute the most frequent breast radiotherapy (RT) acute side effects. The aim of this study was to compare the predictive value of tissue-derived radiomics features to the total breast volume (TBV) for the moist cells epitheliolysis as a surrogate for skin inflammation, and edema. Radiomics features were extracted from computed tomography (CT) scans of 252 breast cancer patients from two volumes of interest: TBV and glandular tissue (GT). Machine learning classifiers were trained on radiomics and clinical features, which were evaluated for both side effects. The best radiomics model was a least absolute shrinkage and selection operator (LASSO) classifier, using TBV features, predicting moist cells epitheliolysis, achieving an area under the receiver operating characteristic (AUROC) of 0.74. This was comparable to TBV breast volume (AUROC of 0.75). Combined models of radiomics and clinical features did not improve performance. Exclusion of volume-correlated features slightly reduced the predictive performance (AUROC 0.71). We could demonstrate the general propensity of planning CT-based radiomics models to predict breast RT-dependent side effects. Mammary tissue was more predictive than glandular tissue. The radiomics features performance was influenced by their high correlation to TBV volume., (© 2024. The Author(s).)

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., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.E.C. received third party funding from the German Research Foundation and the European Union as well as consulting fees from Icotec AG (Switzerland), HMG Systems Engineering GmbH (Germany), Bristol Myers Squibb BMS (Germany). Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events (most speaking appointments include reimbursement of travel costs − does not apply for virtual appointments): Roche, BMS, Brainlab, AstraZeneca, Accuray, Dr. Sennewald, Daiichi Sankyo, Elekta, Medac, med update GmbH. All other authors declare that they have no conflicts of interests., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Background/aim: We investigated grade ≥2 dermatitis in patients irradiated for breast cancer. This study evaluated associations between dermatitis and the season during which radiotherapy took place., Patients and Methods: Associations between the season and grade ≥2 dermatitis were retrospectively evaluated in 327 breast cancer patients. Seasons were March to May (spring), June to August (summer), September to November (autumn), and December to February (winter). Subgroup analyses were performed considering fractionation, radiation technique, treatment volume, radiation boost, and deep-inspiration breath-hold technique. Furthermore, warmer and cooler months were compared., Results: The season had no significant impact on the rate of grade ≥2 dermatitis in the entire cohort (p=0.63) nor in the subgroup analyses (p-values between 0.17 and 0.82). No significant difference in rate was found between warm and cool months., Conclusion: Grade ≥2 dermatitis was not associated with the season during which radiotherapy was performed. This factor may not be important for stratification in prospective trials., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Listeria monocytogenes ( L. monocytogenes ) poses a significant threat to food safety due to its ability to cause severe human illness and its resistance to various antibiotics and environmental conditions. This study investigated the prevalence, serotype distribution, virulence gene profiles, and antimicrobial resistance patterns of L. monocytogenes in ready-to-eat (RTE) food products from Romania. A total of 8151 samples were analyzed, including various processed dairy, bovine, poultry, pork, and fish products. Bacterial isolation was conducted using the classical standard method, followed by confirmation through biochemical and molecular testing. Among the isolated strains, serotypes 1/2a, 1/2b, and 1/2c were identified, with a prevalence of 75% for serotype 1/2a. Additionally, virulence genes specific to listeriolysin O ( hly A) and regulatory factor A ( prf A) were detected in all isolates. Antimicrobial susceptibility testing revealed varying resistance patterns among the L. monocytogenes strains. Trimethoprim-sulfamethoxazole and oxacillin showed the highest prevalence of resistance at 26.92% and 23.07%, respectively. However, all strains remained susceptible to ciprofloxacin, levofloxacin, and moxifloxacin. Notably, 23.07% of the isolates exhibited multidrug resistance, with the most common pattern being resistance to oxacillin, penicillin, and tetracycline. Analysis of antimicrobial resistance genes identified tetracycline resistance genes, particularly tet (C), tet (M), and tet (K), in a significant proportion of isolates. The presence of amp C and dfr D genes was also notable, indicating potential mechanisms of resistance. These results emphasize the necessity for ongoing surveillance of L. monocytogenes in RTE foods and emphasize the importance of thorough monitoring of antimicrobial resistance to guide public health strategies within the European Union.

Background/aim: Pneumonitis is a serious radiotherapy complication. This study, which is a prerequisite for a prospective trial, aimed to identify the prevalence of pneumonitis and risk factors in elderly patients with lung cancer., Patients and Methods: Ninety-eight lung cancer patients aged ≥65 years were included. Seventeen factors were investigated regarding grade ≥2 pneumonitis at 24 weeks following radiotherapy., Results: The prevalence of grade ≥2 pneumonitis at 24 weeks was 27.3%. On univariate analysis, a significant association was observed for mean (ipsilateral) lung dose (MLD; ≤13.0 vs. 13.1-20.0 vs. >20.0 Gy; 0% vs. 24.9% vs. 48.7%). Results were significant also for ≤13.0 vs. >13.0 Gy (0% vs. 37.1%) or ≤20.0 vs. >20.0 Gy (13.4% vs. 48.7%). MLD achieved significance on multivariate analysis., Conclusion: Elderly patients receiving MLDs >13.0 Gy, particularly >20.0 Gy, have a high risk of grade ≥2 pneumonitis. These results are important for designing a prospective trial., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

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., (© 2024. The Author(s).)

Background/aim: Patients with breast cancer receiving adjuvant radiotherapy may experience grade ≥2 dermatitis. In the Interreg-project HeAT, a mobile application (app) reminding patients to perform skin care will be prospectively tested with the goal of decreasing clinically significant radiation dermatitis. This study aimed to identify the prevalence of grade ≥2 dermatitis and risk factors, required for designing the prospective trial., Patients and Methods: In a retrospective study of 327 patients with breast cancer irradiated during 2022-2023, the prevalence of grade ≥2 dermatitis and 23 potential risk factors were investigated., Results: The prevalence of grade ≥2 dermatitis was 31.2%. On multivariate analysis, it was significantly associated with chronic inflammatory disease (p=0.001), significant cardiovascular disease (p<0.001), smoking history >10 pack years (p<0.001), advanced T-stage (p=0.017), normo-fractionation (p<0.001), and radiation boost (p<0.001)., Conclusion: The prevalence of grade ≥2 dermatitis and independent risk factors during adjuvant radiotherapy for invasive breast cancer were identified that contribute to improved patient care and the design of a prospective trial., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background and Purpose: Radiation oncology is an essential component of therapeutic oncology and necessitates well-trained personnel. Multicatheter brachytherapy (MCBT) is one radiotherapeutic option for early-stage breast cancer treatment. However, specialized hands-on training for MCBT is not currently included in the curriculum for residents. A recently developed hands-on brachytherapy workshop has demonstrated promising results in enhancing knowledge and practical skills. Nevertheless, these simulation-based teaching formats necessitate more time and financial resources. Our analyses include computational models for the implementation and delivery of this workshop and can serve as a basis for similar educational initiatives., Methods: This study aimed to assess the cost-effectiveness of a previously developed and evaluated breast brachytherapy simulation workshop. Using a micro-costing approach, we estimated costs at a detailed level by considering supplies, soft- and hardware, and personnel time for each task. This method also allows for a comprehensive evaluation of the costs associated with implementing new medical techniques. The workshop costs were divided into two categories: development and workshop execution. The cost analysis was conducted on a per-participant basis, and the impact on knowledge improvement was measured using a questionnaire., Results: The total workshop costs were determined by considering the initial workshop setup expenses including the development and conceptualization of the course with all involved collaborators, as well as the costs incurred for each individual course. The workshop was found to be financially efficient, with a per-participant cost of € 39, considering the industrial sponsorship provided for brachytherapy equipment. In addition, we assessed the workshop's efficacy by analyzing participant feedback using Likert scale evaluations. The findings indicated a notable enhancement in both theoretical and practical skills among the participants. Moreover, the cost-to-benefit ratio (CBFR) analysis demonstrated a CBFR of € 13.53 for each Likert point increment., Conclusion: The hands-on brachytherapy workshop proved to be a valuable and approximately cost-effective educational program, leading to a significant enhancement in the knowledge and skills of the participants. Without the support of industrial sponsorship, the costs would have been unattainable., (© 2024. The Author(s).)

Purpose: The aim of this study was to evaluate interobserver agreement (IOA) on target volume definition for pancreatic cancer (PACA) within the Radiosurgery and Stereotactic Radiotherapy Working Group of the German Society of Radiation Oncology (DEGRO) and to identify the influence of imaging modalities on the definition of the target volumes., Methods: Two cases of locally advanced PACA and one local recurrence were selected from a large SBRT database. Delineation was based on either a planning 4D CT with or without (w/wo) IV contrast, w/wo PET/CT, and w/wo diagnostic MRI. Novel compared to other studies, a combination of four metrics was used to integrate several aspects of target volume segmentation: the Dice coefficient (DSC), the Hausdorff distance (HD), the probabilistic distance (PBD), and the volumetric similarity (VS)., Results: For all three GTVs, the median DSC was 0.75 (range 0.17-0.95), the median HD 15 (range 3.22-67.11) mm, the median PBD 0.33 (range 0.06-4.86), and the median VS was 0.88 (range 0.31-1). For ITVs and PTVs the results were similar. When comparing the imaging modalities for delineation, the best agreement for the GTV was achieved using PET/CT, and for the ITV and PTV using 4D PET/CT, in treatment position with abdominal compression., Conclusion: Overall, there was good GTV agreement (DSC). Combined metrics appeared to allow a more valid detection of interobserver variation. For SBRT, either 4D PET/CT or 3D PET/CT in treatment position with abdominal compression leads to better agreement and should be considered as a very useful imaging modality for the definition of treatment volumes in pancreatic SBRT. Contouring does not appear to be the weakest link in the treatment planning chain of SBRT for PACA., (© 2023. The Author(s).)

Purpose: The aim of this study was to analyze the heart dose for left-sided breast cancer that can be achieved during daily practice in patients treated with multicatheter brachytherapy (MCBT) accelerated partial-breast irradiation (APBI) and deep-inspiration breath-hold (DIBH) whole-breast irradiation (WBI) using a simultaneous integrated tumor bed boost (SIB)-two different concepts which nonetheless share some patient overlap., Materials and Methods: We analyzed the nominal average dose (Dmean) to the heart as well as the biologically effective dose (BED) and the equivalent dose in 2‑Gy fractions (EQD2) for an α/β of 3 in 30 MCBT-APBI patients and 22 patients treated with DIBH plus SIB. For further dosimetric comparison, we contoured the breast planning target volume (PTV) in each of the brachytherapy planning CTs according to the ESTRO guidelines and computed tangential field plans. Mean dose (Dmean), EQD2 Dmean, and BED Dmean for three dosing schemes were calculated: 50 Gy/25 fractions and two hypofractionated regimens, i.e., 40.05 Gy/15 fractions and 26 Gy/5 fractions. Furthermore, we calculated tangential field plans without a boost for the 22 cases treated with SIB with the standard dosing scheme of 40.05 Gy/15 fractions., Results: MCBT and DIBH radiation therapy both show low-dose exposure of the heart. As expected, hypofractionation leads to sparing of the heart dose. Although MCBT plans were not optimized regarding dose to the heart, Dmean differed significantly between MCBT and DIBH (1.28 Gy vs. 1.91 Gy, p < 0.001) in favor of MCBT, even if the Dmean in each group was very low. In MCBT radiation, the PTV-heart distance is significantly associated with the dose to the heart (p < 0.001), but it is not in DIBH radiotherapy using SIB., Conclusion: In daily practice, both DIBH radiation therapy as well as MCBT show a very low heart exposure and may thus reduce long term cardiac morbidity as compared to currently available long-term clinical data of patients treated with conventional tangential field plans in free breathing. Our analysis confirms particularly good cardiac sparing with MCBT-APBI, so that this technique should be offered to patients with left-sided breast cancer if the tumor-associated eligibility criteria are fulfilled., (© 2023. The Author(s).)

The purpose of this study was to investigate the impact of deep inspiration breath hold (DIBH) on the positioning of thoracic structures and provide treatment planning recommendations for internal mammary chain (IMC) irradiation in breast cancer patients. Thirty-two breast cancer patients from our database underwent both DIBH and free breathing (FB) treatment planning. Contouring of the axillary lymph node clinical target volumes (CTVs: level I, II, III, IV, and IMC according to ESTRO), the internal mammary artery (IMA), the heart, and the left anterior descending artery (LAD) was performed. The following were then analyzed: the distance between the IMA and the heart, the craniocaudal distance in which IMC-CTV and heart coexist, the craniocaudal distance between the lower end of the of level III and IV and the upper end of the heart. Several significant geometric differences were observed between DIBH and FB that explain the efficacy of the DIBH for regional nodal irradiation. In >80% of patients the cranial origin of the LAD lies below the lower edge of the IMC-CTV in DIBH. In addition the slices in which the heart/LAD and IMC-CTV coexist decrease during DIBH. The IMA-heart distance is significantly larger in DIBH. Also the craniocaudal distance between the lower border of the CTV level III and IV and the upper border of the heart is larger in DIBH. The observed mechanisms during DIBH contribute significantly to the dose reduction in regional nodal irradiation. To further enhance the benefits of DIBH for the irradiation of the IMC-CTV, it is recommended to implement steep dose gradients in the caudal plane., Competing Interests: Conflicts of Interest CSE Advisory Boards/Advisor: BMS, Astra Zeneca, Roche, Novo- cure, Daiichi Sankyo, Icotec. Speakers Honoraria: BMS, Astra Zeneca, Roche, Novocure, Daiichi Sankyo, Icotec, Brainlab, varian, Accuray, Zeiss Meditec, Dr. Sennewald, Elekta, Merck Darmstadt, Medac. MND Speakers Honoraria: Astra Zeneca All other authors declare no conflicts of interest., (Copyright © 2023 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.)

Purpose: To quantify neuroanatomical changes using magnetic resonance imaging (MRI) in patients with cerebral metastasized breast cancer after brain radiotherapy (RT)., Methods: Fifteen patients with breast cancer with brain metastases who underwent whole brain RT (WBR), radiosurgery (RS), and/or hypofractionated stereotactic treatment (STX) were examined at four time points (TPs). A total of 48 MRIs were available: prior to RT (TP1), 5-8 months after RT (TP2), 9-11 months after RT (TP3), and >20 months after RT (TP4). Using automatic segmentation, 25 subcortical structures were analyzed. Patients were split into three groups: STX (receiving STX and RS), RS (receiving RS only), and WBR (receiving WBR at least once). After testing for a normal distribution for all values using the Kolmogorov-Smirnov test, a two-sided paired t test was used to analyze volumetric changes. For those values that were not normally distributed, the nonparametric Mann-Whitney test was employed., Results: The left cerebellum white matter ( p = 0.028), the right pallidum ( p = 0.038), and the left thalamus ( p = 0.039) significantly increased at TP2 compared to TP1. The third ventricle increased at all TPs ( p = 0.034-0.046). The left choroid plexus increased at TP3 ( p = 0.037) compared to TP1. The left lateral ventricle increased at TP3 ( p = 0.012) and TP4 ( p = 0.027). Total gray matter showed a trend of volume decline in STX and WBR groups., Conclusions: These findings indicate that alterations in the volume of subcortical structures may act as a sensitive parameter when evaluating neuroanatomical changes and brain atrophy due to radiotherapy. Differences observed for patients who received STX and WBR, but not those treated with RS, need to be validated further.

Evidence from a few small randomized trials and retrospective cohorts mostly including various tumor entities indicates a prolongation of disease free survival (DFS) and overall survival (OS) from local ablative therapies in oligometastatic disease (OMD). However, it is still unclear which patients benefit most from this approach. We give an overview of the several aspects of stereotactic body radiotherapy (SBRT) in extracranial OMD in breast cancer from a radiation oncology perspective. A PubMed search referring to this was conducted. An attempt was made to relate the therapeutic efficacy of SBRT to various prognostic factors. Data from approximately 500 breast cancer patients treated with SBRT for OMD in mostly in small cohort studies have been published, consistently indicating high local tumor control rates and favorable progression-free (PFS) and overall survival (OS). Predictors for a good prognosis after SBRT are favorable biological subtype (hormone receptor positive, HER2 negative), solitary metastasis, bone-only metastasis, and long metastasis-free interval. However, definitive proof that SBRT in OMD breast cancer prolongs DFS or OS is lacking, since, with the exception of one small randomized trial (n = 22 in the SBRT arm), none of the cohort studies had an adequate control group. Further studies are needed to prove the benefit of SBRT in OMD breast cancer and to define adequate selection criteria. Currently, the use of local ablative SBRT should always be discussed in a multidisciplinary tumor board., (© 2022. The Author(s).)

Purpose: Our purpose was to investigate whether liver stereotactic body radiation therapy treatment planning can be harmonized across different treatment planning systems, delivery techniques, and institutions by using a specific prescription method and to minimize the knowledge gap concerning intersystem and interuser differences. We provide best practice guidelines for all used techniques., Methods and Materials: A multiparametric specification of target dose (gross target volume [GTV] D50% , GTV D0.1cc , GTV V90% , planning target volume [PTV] V70% ) with a prescription dose of GTV D50%  = 3 × 20 Gy and organ-at-risk (OAR) limits were distributed with computed tomography and structure sets from 3 patients with liver metastases. Thirty-five institutions provided 132 treatment plans using different irradiation techniques. These plans were first analyzed for target and OAR doses. Four different renormalization methods were performed (PTV Dmin , PTV D98% , PTV D2% , PTV Dmax ). The resulting 660 treatments plans were evaluated regarding target doses to study the effect of dose renormalization to different prescription methods. A relative scoring system was used for comparisons., Results: GTV D50% prescription can be performed in all systems. Treatment plan harmonization was overall successful, with standard deviations for D max , PTV D98% , GTV D98% , and PTV Dmean of 1.6, 3.3, 1.9, and 1.5 Gy, respectively. Primary analysis showed 55 major deviations from clinical goals in 132 plans, whereas in only <20% of deviations GTV/PTV dose was traded for meeting OAR limits. GTV D50% prescription produced the smallest deviation from target planning objectives and between techniques, followed by the PTV Dmax , PTV D98% , PTV D2% , and PTV Dmin prescription. Deviations were significant for all combinations but for the PTV Dmax prescription compared with GTV D50% and PTV D98% . Based on the various dose prescription methods, all systems significantly differed from each other, whereas GTV D50% and PTV D98% prescription showed the least difference between the systems., Conclusions: This study showed the feasibility of harmonizing liver stereotactic body radiation therapy treatment plans across different treatment planning systems and delivery techniques when a sufficient set of clinical goals is given., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Purpose: The current study aimed to compare contouring of glandular tissue only (gCTV) with the clinical target volume (CTV) as defined according to European Society for Radiotherapy and Oncology (ESTRO) guidelines (eCTV) and historically treated volumes (marked by wire and determined by palpation and anatomic landmarks) in breast cancer radiotherapy., Methods: A total of 56 consecutive breast cancer patients underwent treatment planning based solely on anatomic landmarks/wire markings ("wire based"). From these treatment plans, the 50% and 95% isodoses were transferred as structures and compared to the following CT-based volumes: eCTV; a Hounsfield unit (HU)-based automatic contouring of the gCTV; and standardized planning target volumes (PTVs) generated with 1‑cm safety margins (resulting in the ePTVs and gPTVs, respectively)., Results: The 95% isodose volume of the wire-based plan was larger than the eCTV by 352.39 ± 176.06 cm 3 but smaller than the ePTV by 157.58 ± 189.32 cm 3 . The 95% isodose was larger than the gCTV by 921.20 ± 419.78 cm 3 and larger than the gPTV by 190.91 ± 233.49 cm 3 . Patients with larger breasts had significantly less glandular tissue than those with small breasts. There was a trend toward a lower percentage of glandular tissue in older patients., Conclusion: Historical wire and anatomic landmarks-based treatment planning sufficiently covers the glandular tissue and the theoretical gPTV generated for the glandular tissue. Modern CT-based CTV and PTV definition according to ESTRO results in a larger treated volume than the historical wire-based techniques. HU-standardized glandular tissue contouring results in a significantly smaller CTV and might be an option for reducing the treatment volume and improving reproducibility of contouring between institutions., (© 2021. The Author(s).)

Background: Current literature lacks a comparison of lymph node metastases and non-pathological lymph nodes distribution in breast cancer patients. The aim of the current retrospective study was to generate a comprehensive atlas of the lymph node system., Methods: 143 breast cancer patients underwent F-18-FDG-PET/CT (PET/CT) imaging for staging purposes and were diagnosed with regional lymph node metastases. Based on the PET/CT data set a total of 326 lymph node metastases and 1826 non-pathological lymph nodes were detected and contoured manually in the patient collective. Using rigid and deformable registration algorithms all structures were transferred to a template planning CT of a standard patient. Subsequently, a 3D-atlas of the distribution of lymph node metastases and non-pathological lymph nodes were generated and compared to each other., Results: Both, lymph node metastases and non-pathological lymph nodes, accumulated in certain areas ("hot-spots") within the lymphatic drainage system. However large differences regarding the distribution patterns were detected: lymph node metastases hot spots occurred in close proximity to the subclavian vein in level I-III, whereas the non-pathological lymph nodes accumulated mostly (within a wider range) in level I. In level II and III lymph node metastases exceeded clearly the areas in which non-pathological lymph nodes occurred., Conclusion: Lymph node metastases and non-pathological lymph node distribution within the lymph node system differ clearly. Based on our results, an individual adjustment of the CTV in order to include visible lymph nodes in level II and III should be discussed., (© 2022. The Author(s).)

Background: During the last decade, partial breast irradiation (PBI) has gained traction as a relevant treatment option for patients with early-stage low-risk breast cancer after breast-conserving surgery. The TARGIT-A prospective randomized trial compared a "risk-adapted" intraoperative radiotherapy (IORT) approach with 50-kv X-rays (INTRABEAM®) as the PBI followed by optional whole-breast irradiation (WBI) and conventional adjuvant WBI in terms of observed 5-year in-breast recurrence rates. Recently, long-term data were published. Since the first publication of the TARGIT-A trial, a broad debate has been emerged regarding several uncertainties and limitations associated with data analysis and interpretation. Our main objective was to summarize the data, with an emphasis on the updated report and the resulting implications., Summary: From our point of view, the previously unresolved questions still remain and more have been added, especially with regard to the study design, a change in the primary outcome measure, the significant number of patients lost to follow-up, and the lack of a subgroup analysis according to risk factors and treatment specifications., Key Message: Taking into account the abovementioned limitations of the recently published long-term results of the TARGIT-A trial, the German Society of Radiation Oncology (DEGRO) Breast Cancer Expert Panel adheres to its recently published recommendations on PBI: "the 50-kV system (INTRABEAM) cannot be recommended for routine adjuvant PBI treatment after breast-conserving surgery.", Competing Interests: V.S. declares consultation fees from Nucletron Operations BV, an Elekta Company, outside the submitted work. D.K. has received honoraria from Merck Sharp & Dome, outside of the submitted work. F.S. has received a study grant from Intraop Medical. G.F. has received a honorarium from Roche, outside of the submitted work. M.P., R.B., S.C., M.-N.D., J.D., P.F., R.F., Wu.H., Wo.H., T.H., R.S., and W.B. have no conflicts of interest to declare., (Copyright © 2021 by S. Karger AG, Basel.)

The current study aims to determine whether hypofractionated radiotherapy (HF) leads to lower rates of acute radiodermatitis compared to conventional normofractionated radiotherapy (CF). A total of 166 patients with invasive breast cancer or DCIS were included in a prospective cohort study. Evaluation of acute radiodermatitis was obtained before radiotherapy, at the end of the treatment (T1), and 6 weeks after the treatment (T2) using CTCAE (v5.0) scores, the Skindex-16 questionnaire, and ultrasound measurement of the skin. CTCAE and Skindex-16 scores in the CF-group were significantly higher compared to the HF group indicating more pronounced side effects at the end of the treatment (CTCAE: CF-RT 1.0 (IQR: 0.0) vs. HF-RT 0.0 (0.25); p = 0.03; Skindex-16: CF: 20.8 (IQR: 25.8); HF: 8.3 (27.1); p = 0.04). At 6 weeks after the treatment, no significant differences between the two fractionation schemes were observed. Ultrasound based assessment showed that the skin thickness in the treated breast was higher compared to the healthy breast at all time-points. However, no significant difference between HF and CF was seen either at T1 or T2. The current study complements and confirms pre-existing evidence that HF leads to a lower degree of acute radiodermatitis and better patient reported outcome compared to CF at the end of treatment. This should be considered whenever fractionation of adjuvant breast cancer treatment is being discussed.

Purpose: The aim of this study was to investigate whether bone mineral density (BMD) as measured in planning computed tomographies (CTs) by a new method is a risk factor for pelvic insufficiency fractures (PIF) after radio(chemo)therapy (R(C)T) for cervical cancer., Methods: 62 patients with cervical cancer who received definitive or adjuvant radio(chemo)therapy between 2013 and 2017 were reviewed. The PIF were detected on follow-up magntic resonance imaging (MRI). The MRI of the PIF patients was registered to the planning CT and the PIF contoured. On the contralateral side of the fracture, a mirrored structure of the fracture was generated (mPIF). For the whole sacral bone, three lumbar vertebrae, the first and second sacral vertebrae, and the PIF, we analyzed the BMD (mg/cm 3 ), V50Gy, Dmean, and Dmax., Results: Out of 62 patients, 6 (9.7%) had a fracture. Two out of the 6 patients had a bilateral fracture with only one of them being symptomatic. PIF patients showed a significantly lower BMD in the sacral and the lumbar vertebrae (p < 0.05). The BMD of the contoured PIF, however, when comparing to the mPIF, did not reach significance (p < 0.49). The difference of the V50Gy of the sacrum in the PIF group compared to the other (OTH) patients, i.e. those without PIF, did not reach significance., Conclusion: The dose does not seem to have a relevant impact on the incidence of PIF in our patients. One of the predisposing factors for developing PIF after radiotherapy seems to be the low BMD. We presented an easy method to assess the BMD in planning CTs.

Background: The purpose of this study is to detect a correlation between the preradiation tumor staging and the relative volumetric regression of the primary tumor through external beam radiation therapy (EBRT)., Methods: Clinical data of 32 patients with a mean age of 60±12 years treated with primary radiation therapy (RT) of cervical carcinoma were analyzed. Union Internationale Contre le Cancer (UICC) stages were T1 = 4 patients, T2 = 15 patients, T3 = 8 patients, T4 = 5 patients; N1 = 26 patients, N0 = 6 patients; and M0 = 25 patients, M1 = 7 patients. All patients received pelvic magnetic resonance imaging (MRI) before RT as well as during RT. The cervical primary tumor was delineated as gross tumor volume (ptGTV) in T2-weighted MRI sequences. We compared ptGTV reduction by stage, lymph node status, metastatic status, and grading., Results: Mean ptGTV reduction during RT was 61.4±28.9%. T1 tumors shrank by 88.2±13.4%, T2 by 67.6±28.7%, T3 by 50.8±23.6%, and T4 by 38.7±27.2%. The difference in tumor shrinkage was statistically significant between the lower T stages and the higher T stages ( p < 0.05). There was no statistical difference in the mean ptGTV before treatment in the group with lymph node metastases (LNM) (54.1±47.7 cm 3 ) as compared to the group without LNM (76.6±52.2 cm 3 ). Nonetheless, ptGTV shrank significantly differently: by 68.9±25.7% (N1 patients) and by 29.0±17.7% (N0 patients). No significant differences in ptGTV shrinkage were observed in M0 versus M1 and G2 versus G3 tumors., Conclusion: There is a correlation between mean ptGTV reduction during EBRT and tumor stages. Tumors with higher T stages shrank less under radiation treatment, and the ptGTV of N1 patients responded better than that of N0 patients.

Moderate hypofractionation is the standard of care for adjuvant whole-breast radiotherapy after breast-conserving surgery for breast cancer. Recently, 10-year results from the FAST and 5‑year results from the FAST-Forward trial evaluating adjuvant whole-breast radiotherapy in 5 fractions over 5 weeks or 1 week have been published. This article summarizes recent data for moderate hypofractionation and results from the FAST and FAST-Forward trial on ultra-hypofractionation. While the FAST trial was not powered for comparison of local recurrence rates, FAST-Forward demonstrated non-inferiority for two ultra-hypofractionated regimens in terms of local control. In both trials, the higher-dose experimental arms resulted in elevated rates of late toxicity. For the lower dose experimental arms of 28.5 Gy over 5 weeks and 26 Gy over 1 week, moderate or marked late effects were similar in the majority of documented items compared to the respective standard arms, but significantly worse in some subdomains. The difference between the standard arm and the 26 Gy of the FAST-Forward trial concerning moderate or marked late effects increased with longer follow-up in disadvantage of the experimental arm for most items. For now, moderate hypofractionation with 40-42.5 Gy over 15-16 fractions remains the standard of care for the majority of patients with breast cancer who undergo whole-breast radiotherapy without regional nodal irradiation after breast-conserving surgery.

Background: Many patients experience recurrence of prostate cancer after radical prostatectomy., Objective: The aim of this study was to visually analyze typical patterns of lymph node (LN) involvement for prostate cancer (PC) patients with biochemical recurrence after radical prostatectomy and lymphadenectomy by creating a color-coded heat map using gallium-68 prostate-specific membrane antigen positron emission tomography ( 68 Ga-PSMA-PET) imaging. Further, we evaluated which LNs were covered by the Radiation Therapy Oncology Group (RTOG) clinical target volume (CTV) contouring guidelines., Design, Setting, and Participants: A total of 1653 68 Ga-PSMA-PET/computed tomography (CT) datasets were screened retrospectively. After meeting the eligibility criteria, 233 patients with 799 LN metastases were included in our study., Outcome Measurements and Statistical Analysis: We created a comprehensive three-dimensional color-coded LN atlas. Further, the coverage of LN metastases by RTOG CTV was assessed and stratification for risk factors was performed., Results and Limitations: In the overall, mainly high risk, collective, complete coverage by the standard RTOG CTV was accomplished in 31.0% of all LN metastases. The vast majority of uncovered LNs are situated in the para-aortal, pararectal, paravesical, preacetabular, presacral, and inguinal regions. Concerning examined stratification factors, prostate-specific antigen (PSA) levels at the time of PET/CT imaging had the highest predictive value for extrapelvic metastatic LN spread. Every increase of 1 ng/mL in PSA raises the risk of metastases outside the CTV by a factor of 1.43., Conclusions: We developed the first LN atlas for patients with recurrent PC using a heat map technique, in order to illustrate hot spots of LN recurrence. The vast majority of detected LNs are not covered by a standard CTV as recommended by the RTOG. Application of the standard RTOG CTV for pelvic irradiation in the salvage setting for high-risk PC patients seems to be inappropriate., Patient Summary: We visualized typical lymph node recurrence sites for patients after prostate cancer surgery., (Copyright © 2020 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Following neoadjuvant chemotherapy for breast cancer, postoperative systemic therapy, also called post-neoadjuvant treatment, has been established in defined risk settings. We reviewed the evidence for sequencing of postoperative radiation and chemotherapy, with a focus on a capecitabine and trastuzumab emtansine (T-DM1)-based regimen., Methods: A systematic literature search using the PubMed/MEDLINE/Web of Science database was performed. We included prospective and retrospective reports published since 2015 and provided clinical data on toxicity and effectiveness., Results: Six studies were included, five of which investigated capecitabine-containing regimens. Of these, four were prospective investigations and one a retrospective matched comparative analysis. One randomized prospective trial was found for T‑DM1 and radiotherapy. In the majority of these reports, radiation-associated toxicities were not specifically addressed., Conclusion: Regarding oncologic outcome, the influence of sequencing radiation therapy with maintenance capecitabine chemotherapy in the post-neoadjuvant setting is unclear. Synchronous administration of capecitabine is feasible, but reports on possible excess toxicities are partially conflicting. Dose reduction of capecitabine should be considered, especially if normofractionated radiotherapy is used. In terms of tolerance, hypofractionated schedules seem to be superior in terms of toxicity in concurrent settings. T‑DM1 can safely be administered concurrently with radiotherapy.

Purpose: This consensus statement from the Breast Cancer Working Group of the German Society for Radiation Oncology (DEGRO) aims to define practical guidelines for accelerated partial-breast irradiation (APBI)., Methods: Recent recommendations for relevant aspects of APBI were summarized and a panel of experts reviewed all the relevant literature. Panel members of the DEGRO experts participated in a series of conferences, supplemented their clinical experience, performed a literature review, and formulated recommendations for implementing APBI in clinical routine, focusing on patient selection, target definition, and treatment technique., Results: Appropriate patient selection, target definition for different APBI techniques, and basic rules for appropriate APBI techniques for clinical routine outside of clinical trials are described. Detailed recommendations for APBI in daily practice, including dose constraints, are given., Conclusion: Guidelines are mandatory to assure optimal results of APBI using different techniques.

Aim and Background: To assess the use of hypofractionated (HG-RT) versus normofractionated radiation therapy (NF-RT) in Breast Cancer in German speaking countries., Materials and Methods: Between July 2017 and August 2017, an email-based survey was sent to all 1408 physicians that are members of the German Society of Radiation Oncology (DEGRO). The survey was completed by 180 physicians including 10 private practice owners and 52 heads of departments. The majority (82.1%) of the participants had >15 years of experience in radiation therapy (RT)., Results: The majority (83.9%) of the heads of the departments agreed on using the normofractionated regimen of RT as standard treatment for breast cancer. Several physicians were skeptical about HF-RT with 6.5% of the heads refusing to use HF-RT. 40.3% of the departments had not seen the new German guidelines suggesting HF-RT as the standard treatment for all patients as positive or merely adopted a neutral position toward the guidelines (33.9%). The main points of criticism were increased side effects, an impaired toxicity profile and insufficient data. Most departments (46.8%) that perform HF-RT do so in an individual based manner., Conclusions: HF-RT remains controversial in German speaking countries. Our data shows that NF-RT remains the predominant method of treatment. HF-RT is only used in a defined group of patients as most German physicians agree that particular patients, especially those at higher risk of RT late effects, may benefit from a less intense, extended fractionation schedule., (© 2020 Published by Elsevier B.V. on behalf of Greater Poland Cancer Centre.)

Objective: Tangential field irradiation in breast cancer potentially treats residual tumor cells in the axilla after sentinel lymph node biopsy (SLNB). In recent years, hypofractionated radiotherapy has gained importance and currently represents the recommended standard in adjuvant breast cancer treatment for many patients. So far, the impact of hypofractionation on the effect of incidental lymph node irradiation has not be addressed., Materials and Methods: Biological effective dose (BED) and tumor control probability (TCP) were estimated for four different hypofractionated radiation schemes (42.50 Gy in 16 fractions [Fx]; 40.05 Gy in 15 Fx; 27 Gy in 5 Fx; and 26 in 5 Fx) and compared to conventional fractionation (50 Gy in 25 Fx). For calculation of BED and TCP, a previously published radiobiological model with an α/β ratio of 4 Gy was used. The theoretical BED and TCP for incidental irradiation between 0 and 100% of the prescribed dose were evaluated. Subsequently, we assessed BED and TCP in 431 axillary lymph node metastases., Results: The extent of incidental lymph node irradiation and the fractionation scheme have a direct impact on BED and TCP. The estimated mean TCP in the axillary nodes ranged from 1.5 ± 6.4% to 57.5 ± 22.9%, depending on the patient's anatomy and the fractionation scheme. Hypofractionation led to a significant reduction of mean TCP of lymph node metastases for all schedules., Conclusion: Our data indicate that hypofractionation might affect the effectiveness of incidental radiotherapy in the axilla. This is particularly relevant for patients with positive sentinel lymph nodes who receive SLNB only.

Purpose: In patients undergoing chemoradiation for esophageal squamous cell carcinoma (ESCC), the extent of elective nodal irradiation (ENI) is still discussed controversially. This study aimed to analyze patterns of lymph node metastases and their correlation with the primary tumor using 18 F‑fludeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) scans., Methods: 102 ESCC patients with pre-treatment FDG-PET/CT scans were evaluated retrospectively. After exclusion of patients with low FDG uptake and patients without FDG-PET-positive lymph node metastases (LNM), 76 patients were included in the final analysis. All LNM were assigned to 16 pre-defined anatomical regions and classified according to their position relative to the primary tumor (above, at the same height, or below the primary tumor). In addition, the longitudinal distance to the primary tumor was measured for all LNM above or below the primary tumor. The craniocaudal extent (i.e., length) of the primary tumor was measured using FDG-PET imaging (L PET ) and also based on all other available clinical and imaging data (endoscopy, computed tomography, biopsy results) except FDG-PET (L CT/EUS )., Results: Significantly more LNM were identified with 18 F‑FDG-PET/CT (177 LNM) compared to CT alone (131 LNM, p < 0.001). The most common sites of LNM were paraesophageal (63% of patients, 37% of LNM) and paratracheal (33% of patients, 20% of LNM), while less than 5% of patients had supraclavicular, subaortic, diaphragmatic, or hilar LNM. With regard to the primary tumor, 51% of LNM were at the same height, while 25% and 24% of lymph node metastases were above and below the primary tumor, respectively. For thirty-three LNM (19%), the distance to the primary tumor was larger than 4 cm. No significant difference was seen between L CT/EUS (median 6 cm) and L PET (median 6 cm, p = 0.846) CONCLUSION: 18 F‑FDG-PET can help to identify subclinical lymph node metastases which are located outside of recommended radiation fields. PET-based involved-field irradiation might be the ideal compromise between small treatment volumes and decreasing the risk of undertreatment of subclinical metastatic lymph nodes and should be further evaluated.

Background: The aim of our study was to assess the feasibility and oncologic outcomes in patients treated with spinal (SI) or craniospinal irradiation (CSI) in patients with leptomeningeal metastases (LM) and to suggest a prognostic score as to which patients are most likely to benefit from this treatment., Methods: Nineteen patients treated with CSI at our institution were eligible for the study. Demographic data, primary tumor characteristics, outcome and toxicity were assessed retrospectively. The extent of extra-CNS disease was defined by staging CT-scans before the initiation of CSI. Based on outcome parameters a prognostic score was developed for stratification based on patient performance status and tumor staging., Results: Median follow-up and overall survival (OS) for the whole group was 3.4 months (range 0.5-61.5 months). The median overall survival (OS) for patients with LM from breast cancer was 4.7 months and from NSCLC 3.3 months. The median OS was 7.3 months, 3.3 months and 1.5 months for patients with 0, 1 and 2 risk factors according to the proposed prognostic score (KPS < 70 and the presence of extra-CNS disease) respectively. Nonhematologic toxicities were mild., Conclusion: CSI demonstrated clinically meaningful survival that is comparable to the reported outcome of intrathecal chemotherapy. A simple scoring system could be used to better select patients for treatment with CSI in this palliative setting. In our opinion, the feasibility of performing CSI with modern radiotherapy techniques with better sparing of healthy tissue gives a further rationale for its use also in the palliative setting.

Background: Gene expression assays are increasingly used for decision-making regarding adjuvant chemotherapy in patients with hormone receptor-positive, HER2-negative breast cancer. There are some clinical situations in which there is also a need for better prognostic and predictive markers to better estimate the amount of benefit from adjuvant radiotherapy. The rising availability of gene expression analyses prompts the question whether their results can also be used to guide clinical decisions regarding adjuvant radiation., Summary: Multiple studies suggest a correlation between results from gene expression assays and locoregional recurrence rates. Only few publications addressed the predictive value of results from gene expression analysis for the role of adjuvant radiotherapy in different settings., Key Messages: To date, the available evidence on the possible predictive value of gene expression assays for radiotherapy does not support their inclusion into the decision-making process for adjuvant radiation. This is due to methodological weaknesses and limitations regarding patient selection, the nonrandomized design of all studies in terms of radiotherapy use, and limited availability of tissue from prospective trials. Thus, utilization of the present knowledge for clinical indication of radiotherapy should be very cautious., Competing Interests: D.K. has received honoraria from Merck Sharp and Dome. R.B., W.B., M.N.D., J.D., P.F., R.F., W. Haase, W. Harms, T.H., M.D.P., F.S., R. Souchon, F.W., and R. Sauer declare that they have no conflicts of interest., (Copyright © 2020 by S. Karger AG, Basel.)

Background: Tremendous changes have occurred in the treatment of breast cancer. This paper reviews and unifies the available data on modern axillary management of breast cancer patients with focus on the target volume delineation for regional nodal irradiation according to the most important contouring guidelines, the European Society for Radiotherapy and Oncology (ESTRO) and the Radiation Therapy and Oncology Group (RTOG)., Summary: The use of extensive radiotherapy target volumes (level I, II, III, IV) is probably not necessary for all patients to reproduce the clinical benefit shown in the available randomized trials (EORTC, MA.20, AMAROS, Z0011). Nevertheless, given the results in the MA.20 trial, where the patients received more modern systemic therapies and high irradiation doses in the medial paraclavicular region (level IV) and level II, it can be justified to include these regions completely in selected high-risk patients., Key Messages: High-tangent irradiation results in a similar dose distribution in axillary levels I and II compared to the AMAROS treatment field design in some patients. This supports earlier assumptions that irradiation may have accounted for the good results after sentinel lymph node dissection alone in the Z0011 trial. The ESTRO and RTOG clinical target volume (CTV) definitions cover sufficiently the metastatic lymph node hotspots, with a better coverage for the ESTRO CTV. Further, contouring according to the ESTRO would spare a significantly larger part of the healthy lymphatic system, making it our preferred contouring atlas. Modern radiotherapy techniques, such as deep inspiration breath hold, should be cautiously employed in patients treated according to the inclusion criteria of the Z0011 as it will result in a lower dose to the axillary levels., Competing Interests: The author has no conflict of interest to declare., (Copyright © 2020 by S. Karger AG, Basel.)

Objective: The purpose of this study was to estimate the dose distribution from randomized trials (MA.20, EORTC 22922-10925 (EORTC), AMAROS and the Z0011 trial) on lymph node (LN) irradiation on a large LN atlas., Methods: 580 F 18 -FDG-PET/CT positive LN metastases of 235 patients were transferred rigidly and non-rigidly to three "template CTs" (standard, obese and slender patient). Further, the LN clinical target volumes (CTVs) were contoured according to the ESTRO-guidelines. Treatment plans were designed (each for the left and right side) for all patients based on the study protocols of the MA.20, EORTC, AMAROS and Z0011 trial. Subsequently, the dose distribution in the ESTRO-CTVs and in the 580 LNs were assessed., Results: Our results reveal variable dose coverage (26.8 ± 17.3 Gy-53.0 ± 1.8 Gy) in the targeted LN areas (ESTRO-CTV and LN) in dependence of the treatment planning design and the patients' body shape. None of the treatment plan designs provided full dose coverage to the lymphatic drainage system. High tangent irradiation resulted in a similar dose distribution in L I and II compared to the AMAROS field design., Conclusion: Inclusion of the entire lymphatic system may not be necessary for all patients to reproduce the oncologic benefit shown in the randomized LN-irradiation trials. Inclusion of axillary level II and extension of the supraclavicular CTV can be considered in selected high-risk patients, based on dose recalculation of the MA.20 trial. Further, our results amplify earlier assumptions that irradiation may have accounted for the good results after SLND alone in the Z0011 trial., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Skin-sparing (SSME) and nipple-sparing mastectomy (NSME) were developed to improve the cosmetic results for breast cancer (BC) patients, both allowing for immediate breast reconstruction. Recommendations for post-mastectomy radiotherapy (PMRT) are primarily derived from trials where patients were treated by standard mastectomies. Due to their more conservative character, SSME and especially NSME potentially leave more glandular tissue at risk for subclinical disease., Methods: Rates and sites of locoregional failures following SSME and NSME plus/minus reconstruction were analyzed regarding tumor stage and biological risk factors. In particular, the role of PMRT in "intermediate"-risk and early stage high-risk breast cancer patients was revisited. Implications on targeting and dose delivery of PMRT were critically reviewed., Results: The value of PMRT in stage III BC remains undisputed. For node-negative BC patients, the majority of reports classify clinical and biological features such as tumor size, close surgical margins, premenopausal status, multicentricity, lymphangiosis, triple-negativity, HER2-overexpression, and poor tumor grading as associated with higher rates of locoregional relapse, thus, building an "intermediate" risk group. Surveys revealed that the majority of radiation oncologists use risk-adaptive models also considering the number of coinciding factors for the estimation of recurrence probability following SSME and NSME. Constellations with a 10-year locoregional recurrence risk of >10% are usually triggering the indication for PMRT. There was no common belief that the amount of residual tissue, e.g., tissue thickness over flaps, serves as additional decision aid. Modern treatment planning can ensure optimal dose distribution for PMRT in almost all patients with SSME. There are no reliable data supporting a reduction of the treatment volume from the CTV chest wall, e.g., to the nipple-areola complex, to the dorsal aspect behind the implant volume, the pectoralis muscle, nor the regional interpectoral, axillary, or complete regional lymph nodes only. The omission of a skin bolus in intermediate-risk BC does not compromise oncological safety., Conclusions: For intermediate-risk as well as early stage high-risk BC patients, the DEGRO Breast Cancer Expert Panel recommends the use of PMRT following SSME and NSME when a 10-year locoregional recurrence risk is likely to be greater than 10%, as estimated by clinical and biological risk factors. Subvolume-only radiation is discouraged outside of trials. The impact of adequate systemic treatment and the value of radiotherapy on optimal locoregional tumor control, with the goal of less than 5% LRR at 10-years follow-up, has to be verified in prospective trials.

Purpose: The aim of this review was to analyze the respective efficacy of various heart-sparing radiotherapy techniques., Material and Methods: Heart-sparing can be performed in three different ways in breast cancer radiotherapy: by seeking to keep the heart out of treated volumes (i.e. by prone position or specific breathing techniques such as deep inspiration breath-hold [DIBH] and/or gating), by solely irradiating a small volume around the lumpectomy cavity (partial breast irradiation, PBI), or by using modern radiation techniques like intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT) or protons. This overview presents the available data on these three approaches., Results: Studies on prone position are heterogeneous and most trials only refer to patients with large breasts; therefore, no definitive conclusion can be drawn for clinical routine. Nonetheless, there seems to be a trend toward better sparing of the left anterior descending artery in supine position even for these selected patients. The data on the use of DIBH for heart-sparing in breast cancer patients is consistent and the benefit compared to free-breathing is supported by several studies. In comparison with whole breast irradiation (WBI), PBI has an advantage in reducing the heart dose. Of note, DIBH and PBI with multicatheter brachytherapy are similar with regard to the dose reduction to heart structures. WBI by IMRT/VMAT techniques without DIBH is not an effective strategy for heart-sparing in breast cancer patients with "standard" anatomy. A combination of DIBH and IMRT may be used for internal mammary radiotherapy., Conclusion: Based on the available findings, the DEGRO breast cancer expert panel recommends the use of DIBH as the best heart-sparing technique. Nonetheless, depending on the treatment volume and localization, other techniques may be employed or combined with DIBH when appropriate.

Purpose: Pathogenesis of brain metastases/meningeal cancer and the emotional and neurological outcomes are not yet well understood. The hypothesis of our study is that patients with leptomeningeal cancer show volumetric differences in brain substructures compared to patients with cerebral metastases., Methods: Three groups consisting of female breast cancer patients prior to brain radiotherapy were compared. Leptomeningeal cancer patients (LMC Group), oligometastatic patients (1-3 brain metastases) prior to radiosurgery (OMRS Group) and patients prior to whole brain radiation (WB Group) were included. All patients had MRI imaging before treatment. T1 MRI sequences were segmented using automatic segmentation. For each patient, 14 bilateral and 11 central/median subcortical structures were tested. Overall 1127 structures were analyzed and compared between groups using age matched two-sided t-tests., Results: The average age of patients in the OMRS group was 60.8 years (± 14.7), 65.3 (± 10.3) in the LMC group and 62.6 (± 10.2) in the WB group. LMC patients showed a significantly larger fourth ventricle compared to OMRS (p = 0.001) and WB (p = 0.003). The central corpus callosum appeared smaller in the LMC group (LMC vs OMRS p = 0.01; LMC vs WB p = 0.026). The right amygdala in the WB group appeared larger compared with the OMRS (p = 0.035)., Conclusions: Differences in the size of brain substructures of the three groups were found. The results appear promising and should be taken into account for further prospective studies also involving healthy controls. The volumetrically determined size of the fourth ventricle might be a helpful diagnostic marker in the future.

Background: Oncoplastic surgery techniques lead to a rearrangement of the breast tissue and impede target definition during adjuvant radiotherapy (RT). The aim of this study was to assess local control rates after immediate oncoplastic surgery and adjuvant RT., Methods: This study comprises 965 patients who underwent breast-conserving therapy and adjuvant RT between 01/2000 and 12/2005. 288 patients received immediate oncoplastic surgery (ONC) and 677 patients breast-conserving surgery only (NONC). All patients were treated with adjuvant external tangential-beam RT (total dose: 50/50.4 Gy; fraction dose 1.8/2.0 Gy). An additional boost dose of 10-16 Gy to the primary tumor bed was given in 900 cases (93.3%). Local control rates (LCR), Progression free survival (PFS) and overall survival (OS) were assessed retrospectively after a median follow-up period of 67 (Q25-Q75: 51-84) months., Results: No significant difference was found between ONC and NONC in regard to LCR (5-yr: ONC 96.8% vs. NONC 95.3%; p = 0.25). This held also true for PFS (5-yr: ONC 92.1% vs. NONC 89.3%; p = 0.09) and OS (5-yr: ONC 96.0% vs. NONC 94.8%; p = 0.53). On univariate analyses G2-3 (p = 0.04), a younger age (p = 0.01), T-stage (p < 0.01) lymph node involvement (p < 0.01) as well as triple negative tumors (p < 0.01) were identified as risk factors for local recurrence. In a propensity score stratified Cox-regression model no significant impact of oncoplastic surgery on local control rate was found (HR: 2.05, 95% CI [0.93; 4.51], p = 0.08)., Conclusion: Immediate oncoplastic surgery seems not to affect the effectiveness of adjuvant whole breast RT on local control rates in breast cancer patients.

Purpose/objective(s): Along with breast-conserving surgery (BCS), adjuvant radiotherapy (RT) of patients with early breast cancer plays a crucial role in the oncologic treatment concept. Conventionally, irradiation is carried out with the aid of tangentially arranged fields. However, more modern and more complex radiation techniques such as IMRT (intensity-modulated radio therapy) are used more frequently, as they improve dose conformity and homogeneity and, in some cases, achieve better protection of adjacent risk factors. The use of this technique has implications for the incidental- and thus unintended- irradiation of adjacent loco regional lymph drainage in axillary lymph node levels I-III and internal mammary lymph nodes (IMLNs). A comparison of a homogeneous "real-life" patient collective, treated with helical tomotherapy (TT), patients treated with 3D conformal RT conventional tangentially arranged fields (3DCRT) and deep inspiration breath hold (3DCRT-DIBH), was conducted., Materials/methods: This study included 90 treatment plans after BCS, irradiated in our clinic from January 2012 to August 2016 with TT (n = 30) and 3D-CRT (n = 30), 3DCRT DIBH (n = 30). PTVs were contoured at different time points by different radiation oncologists (> 7). TT was performed with a total dose of 50.4 Gy and a single dose of 1.8 Gy with a simultaneous integrated boost (SIB) to the tumor cavity (TT group). Patients irradiated with 3DCRT/3DCRT DIBH received 50 Gy à 2 Gy and a sequential boost. Contouring of lymph drainage routes was performed retrospectively according to RTOG guidelines., Results: Average doses (DMean) in axillary lymph node Level I/Level II/Level III were 31.6 Gy/8.43 Gy/2.38 Gy for TT, 24.0 Gy/11.2 Gy/3.97 Gy for 3DCRT and 24.7 Gy/13.3 Gy/5.59 Gy for 3DCRT-DIBH patients. Internal mammary lymph nodes (IMLNs) Dmean were 27.8 Gy (TT), 13.5 Gy (3DCRT), and 18.7 Gy (3DCRT-DIBH). Comparing TT to 3DCRT-DIBH dose varied significantly in all axillary lymph node levels and the IMLNs. Comparing TT to 3DCRT significant dose difference in Level I and IMLNs was observed., Conclusion: Dose applied to locoregional lymph drainage pathways varies comparing tomotherapy plans to conventional tangentially arranged fields. Studies are warranted whether dose variations influence loco-regional spread and must have implications for target volume definition guidelines.

Aim: To report long-term data regarding biochemical control and late toxicity of simultaneous integrated boost intensity modulated radiotherapy (SIB-IMRT) with tomotherapy in patients with localized prostate cancer., Background: Dose escalation improves cancer control after curative intended radiation therapy (RT) to patients with localized prostate cancer, without increasing toxicity, if IMRT is used., Materials and Methods: In this retrospective analysis, we evaluated long-term toxicity and biochemical control of the first 40 patients with intermediate risk prostate cancer receiving SIB-IMRT. Primary target volume (PTV) 1 including the prostate and proximal third of the seminal vesicles with safety margins was treated with 70 Gy in 35 fractions. PTV 2 containing the prostate with smaller safety margins was treated as SIB to a total dose of 76 Gy with 2.17 Gy per fraction. Toxicity was evaluated using an adapted CTCAE-Score (Version 3)., Results: Median follow-up of living patients was 66 (20-78) months. No late genitourinary toxicity higher than grade 2 has been reported. Grade 2 genitourinary toxicity rates decreased from 58% at the end of the treatment to 10% at 60 months. Late gastrointestinal (GI) toxicity was also moderate, though the prescribed PTV Dose of 76 Gy was accepted at the anterior rectal wall. 74% of patients reported any GI toxicity during follow up and no toxicity rates higher than grade 2 were observed. Grade 2 side effects were reported by 13% of the patients at 60 months. 5-year freedom from biochemical failure was 95% at our last follow up., Conclusion: SIB-IMRT using daily MV-CT guidance showed excellent long-term biochemical control and low toxicity rates.

Background: The aim of this study was to compare dose-volume histogram (DVH) with dose-mass histogram (DMH) parameters for treatment of left-sided breast cancer in deep inspiration breath-hold (DIBH) and free breathing (FB). Additionally, lung expansion and anatomical factors were analyzed and correlated to dose differences., Methods: For 31 patients 3D conformal radiation therapy plans were retrospectively calculated on FB and DIBH CTs in the treatment planning system. The calculated doses, structures and CT data were transferred into MATLAB and DVHs and DMHs were calculated. Mean doses (Dmean), volumes and masses receiving certain doses (Vx, Mx) were determined for the left lung and the heart. Additionally, expansion of the left lung was evaluated using deformable image registration. Differences in DVH and DMH dose parameters between FB and DIBH were statistically analyzed and correlated to lung expansion and anatomical factors., Results: DIBH reduced Dmean (DVH) and relative V20 (V20 [%]) of the left lung in all patients, on average by - 19 ± 9% (mean ± standard deviation) and - 24 ± 10%. Dmean (DMH) and M20 [%] were also significantly reduced (- 12 ± 11%, - 16 ± 13%), however 4 patients had higher DMH values in DIBH than in FB. Linear regression showed good correlations between DVH and DMH parameters, e.g. a dosimetric benefit smaller than 8.4% for Dmean (DVH) in DIBH indicated more irradiated lung mass in DIBH than in FB. The mean expansion of the left lung between FB and DIBH was 1.5 ± 2.4 mm (left), 16.0 ± 4.0 mm (anterior) and 12.2 ± 4.6 mm (caudal). No significant correlations were found between expansions and differences in Dmean for the left lung. The heart dose in DIBH was reduced in all patients by 53% (Dmean) and this dosimetric benefit correlated to lung expansion in anterior., Conclusions: Treatment of left-sided breast cancer in DIBH reduced dose to the heart and in most cases the lung dose, relative irradiated lung volume and lung mass. A mass related dosimetric benefit in DIBH can be achieved as long as the volume related benefit is about ≥8-9%. The lung expansion (breathing pattern) showed no impact on lung dose, but on heart dose. A stronger chest breathing (anterior expansion) for DIBH seems to be more beneficial than abdominal breathing.

Background: The aim of this study was to assess the correlations between the levels of blood glucose (BG) and the dose of radiation therapy (RT) to the central gustatory system (GS) in glioblastoma multiforme (GBM) patients., Methods: Thirty-seven GBM patients with regular blood glucose measurements were investigated retrospectively. 59.5% were female and 40.5% male with a median age of 64.3 years (range 27.4-85.6). Diabetes mellitus type 2 (DM2) history, BG levels and dexamethasone (DEXA) medication were assessed. The analyzed central gustatory structures were: solitary tract and nucleus, ventral posteromedial nucleus of the thalamus, sensory tongue area of the postcentral gyrus, anterior part of the insula, frontal operculum, amygdala, hypothalamus. These structures were delineated on magnetic resonance tomographies (MRIs) registered to planning-CTs. All GS doses were transformed in equivalent doses in 2 Gy fraction (EQD2)., Results: Twenty one patients (56.8%) had at least one BG values over 200 mg/dl during RT. There was a difference between average BG in DM2: 192.8 mg/dl (±24.4) and non-DM2 patients: 145.7 mg/dl (±39.5; p = 0.01) but no significant difference in daily DEXA medication - DM2 patients: 7.9 mg/d (±1.9) vs. non-DM2: 9.3 mg/dl (±5.7; p = 0.29). The EQD2 Dmean to the total GS was 36.0Gy (±8.6 Gy). There was a tendency for a higher increase in maximum BG values with more radiation dose to the total GS (b = 1.9, R 2  = 0.103, p = 0.06)., Conclusion: BG levels in GBM patients are in direct correlation to the dose of RT applied to the central GS. GBM patients that undergo RT should thus be closely monitored for changes in BG levels during and after the radiation.

Background: The goal of this study was to investigate if daily dose recalculations are necessary or if less time-consuming approaches can be used to identify dose differences to the planned dose in patients with head and neck cancers (H&N)., Methods: For 12 H&N patients treated with helical tomotherapy, daily dose calculations were performed retrospectively. Four different summation doses (SuDo) were calculated: DayDo (daily dose calculation), MVCTx2, MVCTx5, and MVCTx10 (dose calculations every second, fifth, and tenth fraction). Dose recalculations were depicted on the last contoured mega voltage CT (MVCT). The DayDo was compared to the planned dose and to the less time-consuming SuDo scenarios. The doses were assessed for the planning target volume (PTV) and the organs at risk (OARs): mandible (mand), spinal cord (SC), spinal cord +5 mm (SC+5 mm), parotid glands (PG)., Results: The ipsilateral PG, contralateral PG, and PTV volume decreased by -22.5% (range: -34.8 to 5.2%), -19.5% (-31.5 to 15.8%), and -2.6% (-16.7 to 0.2%), respectively. There was a significant median mean dose (Dmean) dose difference for DayDo compared to the planned dose for PG total of 1.9 Gy (-3.3 to 7.3 Gy). But less time-consuming SuDo compared to DayDo showed statistically significant but not clinically relevant (<2%) dose differences for several organs. Hence the small dose difference to the gold standard (DayDo), we recommend dose recalculations every fifth MVCT in order to identify the occurrence of dose differences compared to the planned dose., Conclusion: Daily dose calculations are the most precise to assess dose differences between actual and planned dose. Dose recalculations on every fifth MVCT (i. e., weekly control CTs) are an applicable and time-saving way of identifying patients with significant dose differences compared to the planned dose.

Purpose: For a large or symptomatic brain metastasis, resection and adjuvant radiotherapy are recommended. Hypofractionated stereotactic radiotherapy (HFSRT) is increasingly applied in patients with a limited number of lesions. Exact target volume definition is critical given the small safety margins. Whilst technical advances have minimized inaccuracy due to patient positioning and radiation targeting, little is known about changes in target volume. This study sought to evaluate potential changes in the resection cavity of a brain metastasis., Methods: In all, 57 patients treated with HFSRT after surgical resection of one brain metastasis between 2008 and 2015 in our institution were included in this study. Gross tumor volume (GTV) of the initial metastasis and the volume of the resection cavity in the post-operative, planning, and follow-up MRIs were measured and compared., Results: The mean cavity size decreased after surgery with the greatest change of -23.4% (±41.5%) occurring between post-operative MRI and planning MRI (p < 0.01). During this time period, the cavity volume decreased, remained stable, and increased in 79.1, 3.5, and 17.4%, respectively. A further decrease of -20.7% (±58.1%) was perceived between planning MRI and first follow-up (p < 0.01). No significant difference in pattern of change could be observed depending on the volume of initial GTV, size of the post-operative resection cavity, initial or post-resection FLAIR (fluid-attenuated inversion recovery) hyper-intensity, postsurgical ischemia, or primary tumor. The resection cavities of patients with post-operative ischemia were significantly larger than resection cavities of patients without ischemia., Conclusion: The resection cavity seems to be very dynamic after surgery. Hence, it remains necessary to use very recent scans for treatment planning.