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Abstract Anal squamous cell carcinoma (ASCC) is associated with immunosuppression and infection with human papillomavirus (HPV). Response to standard chemoradiotherapy (CRT) varies considerably. A comprehensive molecular characterization of CRT resistance is lacking, and little is known about the interplay between tumor immune contexture, host immunity, and immunosuppressive and/or immune activating effects of CRT. Patients with localized ASCC, treated with CRT at three different sites of the German Cancer Consortium (DKTK) were included. Patient cohorts for molecular analysis included baseline formalin fixed paraffin embedded biopsies for immunohistochemistry (n = 130), baseline RNA sequencing (n = 98), peripheral blood immune profiling (n = 47), and serum cytokine measurement (n = 35). Gene set enrichment analysis showed that pathways for IFNγ, IFNα, inflammatory response, TNFα signaling via NF-κB, and EMT were significantly enriched in poor responders (all p

Background: In radiotherapy the timely identification of patients needing intervention and supportive care due to side effects is an important task especially in the outpatient setting. Activity trackers as an increasingly used lifestyle device may enable physicians to monitor patient’s physical activity (PA) and to intervene early during the course of radiotherapy. Objective: The primary aim of this trial was to assess patient acceptance of PA monitoring in an outpatient setting and to correlate changes in PA with toxicity and changes in quality of life. Methods: Patients undergoing radio(chemo-)therapy with a curative intent were eligible to participate in this prospective pilot phase II trial. Patients were instructed to wear a commercially available activity tracker during the course of radiotherapy and four weeks afterwards. Quality of life (QoL) and fatigue was scored using the Functional assessment of Chronic Illness Therapy questionnaire. A linear regression was performed to determine baseline activity and changes in step counts during radiotherapy. Results: We included 23 patients in this trial. Two withdrew consent before the start of treatment, two patients were excluded after prophylactic feeding tube placement and prolonged recovery. Compliance in the remaining 19 patients was high, with availability of step-counts on 92% of the days. Baseline step counts were 6274 for breast cancer patients and 3621 for patients with other entities. Decreasing activity during radiotherapy coincided with the development of side effects and declines in quality of life. Conclusions: Activity trackers as tool to monitor PA during and after radiotherapy were accepted by a majority of the patients included in the current trial. Observed changes in PA correlated with patient reported side effects and QoL in some of the patients.

Introduction: The hybrid magnetic resonance linear accelerator (MRL) has the potential to test novel concepts in breast cancer patients such as daily MR-guided real-time plan adaptation. Before starting clinical trials, preparatory studies for example of the MR-dependent electron stream effect (ESE) are necessary. Material and Methods: To prospectively investigate the ESE, data from 11 patients treated with partial breast irradiation (PBI) at the 1.5 T MRL were evaluated. A bolus was placed on the chin and in vivo dosimetry results were compared with the dose simulated by the treatment planning system (TPS). The same measurements were carried out for three patients treated at a conventional linac. Toxicity and cosmesis were evaluated. Results: Median doses measured and simulated on top/ underneath the bolus were 1.91 / 0.62 Gy and 2.82 / 0.63 Gy, respectively. Median differences between calculations and measurements were 0.8 Gy and 0.1 Gy. At the conventional linac, median measured doses on top/ underneath the bolus were 0.98 and 1.37 Gy. No acute toxicity exceeding grade 2 was recorded. Cosmesis was good or excellent and patient reported outcome measures were mostly scored as none or mild. Conclusion: The dose due to the ESE is low, correctly predicted by the TPS and effectively minimized by a bolus.

Background: Anal cancer (AC) is a malignancy with increasing incidence and commonly treated with radiochemotherapy. Positron-emission tomography-computed tomography (PET/CT) has been shown to improve treatment outcome in various oncological diseases, however, for AC long-term outcome data is sparse. The aim of the present study is therefore to report outcomes in our cohort of PET/CT staged AC patients treated with radiochemotherapy. Methods: Patients with AC who were treated with radiochemotherapy in curative intent were included in this retrospective study if a PET/CT scan was performed pre-therapeutically. Information from PET/CT was considered for nodal and primary target volume definition. Radiotherapy dose to the primary tumor was 50–66 Gy and concomitant chemotherapy included 5-fluorouracil and mitomycin-C. The uptake of 18F-fluorodeoxyglucose (FDG) was quantified using 50%-isocontour volumes of interests (VOIs) and measuring the standardized uptake value (SUV) and the metabolic tumor volume (MTV).18F-FDG uptake was correlated with baseline clinical parameters and long-term oncological outcome. Survival estimates were determined according to Kaplan-Meier. Results: A total of 60 patients were included in this study. Estimates for three-year overall survival (OS) and disease free survival (DFS) were 94.5% and 80%. Five patients developed local (n = 2) or locoregional and local (n = 3) failure. Baseline PET/CT related parameters correlated with primary tumor stage, nodal stage and tumor grading. DFS was independent of T-stage, N-stage and baseline 18F-FDG-uptake. Conclusion: In this cohort of PET/CT staged AC patients, excellent outcomes for DFS were seen. PET-based markers of tumor burden correlate with local stage of AC, however, are not of prognostic relevance for disease-free survival.

Neoadjuvant radiochemotherapy with subsequent total mesorectal excision is the standard of care for locally advanced rectal cancer. While this multimodal strategy has decreased local recurrences rates below 5%, long-term morbidities are considerable in terms of urinary, sexual or bowel functioning. At the same time approximately 10–20% of patients have no evidence of residual tumour in their surgical specimen. Pioneering studies from Brazil have suggested that surgery can safely be omitted in carefully selected patients with a clinical complete response after radiochemotherapy. Although confirmatory studies showed similar results, challenges in terms of optimizing radiochemotherapy for organ-preservation, appropriate selection of patients for non-operative management and the safety of this approach remain. The present review will summarize the current data on organ-preservation in rectal cancer and discuss the challenges that need to be addressed in future trials.

This paper presents a new mesoscopic full field approach for the modeling of microstructural evolutions and mechanical behavior of olivine aggregates. The mechanical framework is based on a reduced crystal plasticity (CP) formulation which is adapted to account for non-dislocation glide strain-accommodating mechanisms in olivine polycrystals. This mechanical description is coupled with a mixed velocity–pressure finite element (FE) formulation through a classical crystal plasticity finite element method (CPFEM) approach. The microstructural evolutions, such as grain boundary migration and dynamic recrystallization, are also computed within a FE framework using an implicit description of the polycrystal through the level-set approach. This numerical framework is used to study the strain localization, at the polycrystal scale, on different types of pre-existing shear zones for thermomechanical conditions relevant to laboratory experiments. We show that both fine-grained and crystallographic textured pre-existing bands favor strain localization at the sample scale. The combination of both processes has a large effect on strain localization, which emphasizes the importance of these two microstructural characteristics (texture and grain size) on the mechanical behavior of the aggregate. Table 1 summarizes the list of the acronyms used in the following.

Abstract Chron’s Disease is a chronic inflammatory intestinal disease, first described at the beginning of the last century. The disease is characterized by the alternation of periods of flares and remissions influenced by a complex pathogenesis in which inflammation plays a key role. Crohn’s disease evolution is mediated by a complex alteration of the inflammatory response which is characterized by alterations of the innate immunity of the intestinal mucosa barrier together with a remodeling of the extracellular matrix through the expression of metalloproteins and increased adhesion molecules expression, such as MAcCAM-1. This reshaped microenvironment enhances leucocytes migration in the sites of inflammation, promoting a TH1 response, through the production of cytokines such as IL-12 and TNF-α. IL-12 itself and IL-23 have been targeted for the medical treatment of CD. Giving the limited success of medical therapies, the treatment of the disease is invariably surgical. This review will highlight the role of inflammation in CD and describe the surgical approaches for the prevention of the almost inevitable recurrence.

Competing Interests: Die Autorinnen/Autoren geben an, dass Ihre Interessenkonflikte im Leitlinienreport dieser Leitlinie aufgelistet sind.

Competing Interests: Die Übersicht über die Interessenkonflikte der Autorinnen und Autoren ist im Anhang des Leitlinienreports veröffentlicht.

Background and Purpose: Combining chemoradiotherapy (CRT) with deep regional hyperthermia (HT) shows promise for enhancing clinical outcomes in selected rectal cancer patients. This study aimed to integrate the evidence and evaluate the efficacy of this combined treatment approach., Materials and Methods: A systematic search of the PubMed, Scopus, and Mendeley databases was performed. This review was conducted according to the PRISMA guidelines. The quality of studies was evaluated using the Newcastle-Ottawa scale (NOS). Random-effects meta-analyses (DerSimonian and Laird) were performed. The primary outcome was pathological complete response (pCR), and secondary endpoints were overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS), and toxicity., Results: In total, 12 studies were included, mostly of moderate quality. Patients with locally advanced rectal cancer (LARC; n = 760) and locally recurrent rectal cancer (LRRC; n = 22) were eligible. The pooled pCR rate was 19% (95% confidence interval [CI]: 16-22%) among all 782 patients and 19% (95%CI:16-23%) among 760 LARC patients. Due to significant study heterogeneity, survival outcomes were pooled by excluding LRRC patients. The pooled 5‑year OS rate among 433 LARC patients was 87% (95%CI: 83-90%). The pooled 5‑year DFS and LRFS in LARC patients were 75% (95%CI: 70-80%) and 95% (95%CI: 92-97%), respectively. There was a lack of consistent reporting of HT treatment parameters and toxicity symptoms among the studies., Conclusion: The collective clinical evidence showed that neoadjuvant CRT combined with HT in rectal cancer patients is feasible, with a 19% pCR rate and excellent survival outcomes in long term follow-up., Competing Interests: Conflict of interest: A. Ademaj, S. Stieb, C. Gani, O.J. Ott, D. Marder, R.A. Hälg, S. Rogers, P. Ghadjar, R. Fietkau, H. Crezee, and O. Riesterer declare that they have no competing interests., (© 2024. The Author(s).)

Background: For radiotherapy of head and neck cancer (HNC) magnetic resonance imaging (MRI) plays a pivotal role due to its high soft tissue contrast. Moreover, it offers the potential to acquire functional information through diffusion weighted imaging (DWI) with the potential to personalize treatment. The aim of this study was to acquire repetitive DWI during the course of online adaptive radiotherapy on an 1.5 T MR-linear accelerator (MR-Linac) for HNC patients and to investigate temporal changes of apparent diffusion coefficient (ADC) values of the tumor and subvolume levels., Methods: 27 patients treated with curative RT on the 1.5 T MR-Linac with at least weekly DWI in treatment position were included into this prospective analysis and divided in four risk groups (HPV-status and localisation). Tumor and lymph node volumes (GTV-P/GTV-N) were delineated on b = 500 s/mm 2 images while ADC maps were calculated using b = 150/200 and 500 s/mm 2 images. Absolute and relative temporal changes of mean ADC values, tumor volumes and a high-risk subvolume (HRS) defined by low ADC tumor voxels (600 < ADC < 900 × 10 -6  mm 2 /s) were analyzed. Relative changes of mean ADC values, tumor volumes and HRS were statistically tested using Wilcoxon-signed-rank test., Results: Median pretreatment ADC value for all patients resulted in 1167 × 10 -6  mm 2 /s for GTV-P and 1002 × 10 -6  mm 2 /s for GTV-N while absolute pretreatment tumor volume yielded 9.1 cm 3 for GTV-P and 6.0 cm 3 for GTV-N, respectively. Pretreatment HRS volumes were 1.5 cm 3 for GTV-P and 1.3 cm 3 for GTV-P and GTV-N. Median ADC values increase during 35 fractions of RT was 49% for GTV-P and 24% for GTV-N during RT. Median tumor volume decrease was 68% and 52% for GTV-P and GTV-N with a median HRS decrease of 93% and 87%. Significant differences from 0 for mean ADC were observed starting from week 1, for tumor volumes from week 2 for GTV-P and week 1 for GTV-N and for HRS in week 1 for GTV-P and week 2 for GTV-N., Conclusion: Longitudinal DWI acquisition in HNC is feasible on a MR-Linac during the course of online adaptive MR-guided radiotherapy. Changes in ADC and volumes can be assessed, but future work needs to explore the potential for biologically guided treatment individualization., Trial Registration: NCT04172753, actual study start: 09.05.2018., Competing Interests: Declarations. Ethics approval and consent to participate: The trial was approved by the local ethical committee (no. 659/2017BO1, NCT04172753) and all patients gave their written informant consent. Consent for publication: Approval for publication of patient images was included in all patients’ written informant consent. Competing interests: The Department of Radiation Oncology Tübingen receives financial and technical support by Elekta, Philips, Dr. Sennewald Medizintechnik, Kaiku Health, TheraPanacea, PTW Freiburg, ITV and Brainlab in the context of research cooperations. The Department of Diagnostic and Interventional Radiology, University of Tübingen reports institutional collaborations, consultation and grants supported Siemens Healthineers, Erlangen, Germany and Bayer Healthcare, Leverkusen, Germany outside this study., (© 2025. The Author(s).)

Background: Preoperative chemoradiotherapy combined with total mesorectal excision (TME) is a standard treatment for locally advanced rectal cancer (LARC). However, lateral pelvic lymph nodes (LPLNs) are often inadequately treated with standard regimens. This study examines the treatment and postoperative outcomes in LARC patients receiving a simultaneous integrated boost (SIB) for LPLNs during long-course chemoradiotherapy., Methods: This retrospective study included high-risk LARC patients (UICC, "Union Internationale Contre le Cancer", stage III) treated with preoperative chemoradiotherapy and SIB to LPLNs. Radiotherapy was delivered to the primary tumor and elective volumes with 50.4 Gy in 28 fractions, and an SIB with a median dose of 60.2 Gy was administered to clinically positive LPLNs. TME quality and postoperative complications were assessed using MERCURY and Clavien-Dindo, respectively. Time-to-event data were analyzed according to Kaplan-Meier., Results: Between 2019 and 2023, 27 patients with high-risk LARC and LPLN metastases were treated with chemoradiotherapy. After a median follow-up of 19 months, 2‑year overall survival was 80%, disease-free survival 80%, and local control of dose-escalated lymph nodes 100%. Three patients were managed nonoperatively after a clinical complete response on endoscopy and imaging. Of the 22 patients who had surgery, only one had complications higher than Clavien-Dindo grade I; TME was graded as MERCURY I in 73%., Discussion and Conclusion: The SIB approach for LPLNs in LARC is feasible, does not increase postoperative morbidity, and achieves excellent local control. This study supports the consideration of dose-escalated radiotherapy for LPLNs to address high local recurrence risks., Competing Interests: Conflict of interest: M. Büttner, S. Baumeister, R. Bachmann, M. Bitzer, H. Bösmüller, D. Wichmann, M. Niyazi, and C. Gani declare that they have no competing interests. The Department of Radiation Oncology receives technical and financial support from Elekta outside the current study. Honoraria: C. Gani (Elekta). Travel expenses: C. Gani, S. Böke, (Elekta)., (© 2025. The Author(s).)

Background and Purpose: Neoadjuvant chemoradiotherapy (NCRT) is a standard treatment option for locally advanced rectal cancer. However, there is still conflicting data about the genetic landscape and potential dynamics during and after NCRT. This study evaluated oncogenic driver mutations before NCRT and investigated corresponding resection samples after treatment., Materials and Methods: In 17 patients the pre-therapeutic biopsy and in ten cases the related resection specimen were investigated by next-generation sequencing using a dedicated cancer panel (708 genes). Oncogenic driver mutations and tumor mutational burden (TMB) were compared pre- and post NCRT to evaluate stability of the genomic landscape. TMB and frequently detected driver mutations were correlated with outcome parameters., Results: In our corresponding tumor samples before and after NCRT 95.2 % of the oncogenic driver mutations could be found in both specimens whereas one ATM and one RYR1 mutation were not detectable after NCRT. TMB decreased in all patients after neoadjuvant treatment. KRAS  ±  TP53 mutations and TMB ≥ 5 were associated with impaired outcome., Conclusion: Most oncogenic driver mutations investigated persisted after neoadjuvant treatment. At the same time, we did not observe ascending TMB after treatment but decline. Thus, NCRT does not seem to induce a relevant number of new driver mutations or mutational burden. Genetic profiling implies the potential to support tumor-informed approaches and outcome estimation in future., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: KC, CG and MN report institutional collaborations including financial and non-financial support by Elekta, Philips, Siemens, Dr. Sennewald, PTW Freiburg, Kaiku and Therapanacea. CS reports institutional grants from Novartis and Illumina as well as research grants from BMS Stiftung Immunonkologie outside the submitted work., (© 2024 The Authors. Published by Elsevier B.V. on behalf of European Society for Radiotherapy and Oncology.)

Background and Purpose: Despite recent advances of online image-guided high-precision patient positioning and adaptation using magnetic resonance imaging (MRI) or cone-beam computed tomography (CT), standard radiation therapy pathway still involves a dedicated simulation scan. The aim of this study was to evaluate the feasibility and planning quality of integrating a simulation-free treatment planning workflow for adaptive online MRI-guided radiation therapy on a 1.5 T MRI linear accelerator (MRI-Linac) in prostate cancer using diagnostic CT (dCT) scans., Materials and Methods: For ten patients with prostate cancer previously treated at the MRI-Linac with adaptive radiation therapy (42.7 Gy in 7 fractions), simulation-free reference plans based on dCT were retrospectively created, and adaptive plans were simulated for the first treatment fraction. Reference and adapted plans derived from both standard and simulation-free workflows were compared with regard to institutional dose/volume criteria, followed by statistical assessment using the paired Wilcoxon signed-rank test with a Bonferroni-corrected significance level of α = 0.025., Results: Simulation-free reference and adapted plans consistently met dose/volume criteria. Statistical analysis revealed no significant differences between both workflows, except median values for near-maximum dose (D2%) in the planning target volume: 44.2 Gy (standard) vs. 44.5 Gy (simulation-free) in reference plans (p = 0.01), and 44.5 Gy vs. 44.6 Gy in adapted plans (p = 0.01)., Conclusion: This study demonstrated the feasibility of simulation-free radiation therapy planning using dCT. Comparable treatment plan quality was observed for both reference and adapted radiation therapy plans in a curative setting for patients with prostate cancer., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

Background: In locally advanced rectal cancer, the prediction of tumor response during and after neoadjuvant treatment remains challenging. In terms of organ preservation, adaptive radiotherapy, and intensified (total) neoadjuvant therapies, biomarkers are desirable for patient stratification., Methods: In 16 patients, weekly blood samples (n = 86) to detect cell-free tumor DNA (ctDNA) during long-course neoadjuvant chemoradiotherapy were analyzed. Data were correlated with initial tumor volumes, MRI response in week 2 and 5 of radiotherapy as well as with pathologic tumor response after resection and outcome parameters., Results: Most patients showed decreasing ctDNA during the course of radiochemotherapy. However, we found heterogenous dynamics of ctDNA and could identify three groups: (1) decline (2) no clear decline and/or late shedding (3) persistence of ctDNA. In seven patients we could detect significant amounts of ctDNA in week 5 or week 6 of treatment. In our pilot cohort, we did not find significant correlations of ctDNA dynamics with pathologic response or outcome parameters. However, patients with distinct decline of ctDNA had larger tumor volumes prior to treatment, and MRI imaging in week 2 and 5 revealed bigger absolute decrease of tumor volumes. If significant levels of ctDNA were found in week 5 and / or 6, patients showed less absolute tumor volume decrease in week 2 and 5., Conclusions: Weekly measurement of ctDNA during radiochemotherapy is feasible and might represent a promising biomarker. Bigger initial primary tumors showed different ctDNA shedding profiles compared with smaller primary tumors and correlations of ctDNA dynamics with early imaging response were found., (© 2024. The Author(s).)

Background and Purpose: Conventional image-guided radiotherapy (conv-IGRT) is standard in prostate cancer (PC) but does not account for inter-fraction anatomical changes. Online-adaptive magnetic resonance-guided RT (OA-MRgRT) may improve organ-at-risk (OARs) sparing and clinical target volume (CTV) coverage. The aim of this study was to analyze accumulated OAR and target doses in PC after OA-MRgRT and conv-IGRT in comparison to pre-treatment reference planning (refPlan)., Material and Methods: Ten patients with PC, previously treated with OA-MRgRT at the 1.5 T MR-Linac (20x3Gy), were included. Accumulated OA-MRgRT doses were determined by deformably registering all fraction's MR-images. Conv-IGRT was simulated through rigid registration of the planning computed tomography with each fraction's MR-image for dose mapping/accumulation. Dose-volume parameters (DVPs), including CTV D50% and D98%, rectum, bladder, urethra, Dmax and V56Gy for OA-MRgRT, conv-IGRT and refPlan were compared using the Wilcoxon signed-rank test. Clinical relevance of accumulated dose differences was analyzed using a normal-tissue complication-probability model., Results: CTV-DVPs were comparable, whereas OA-MRgRT yielded decreased median OAR-DVPs compared to conv-IGRT, except for bladder V56Gy. OA-MRgRT demonstrated significantly lower median rectum Dmax over conv-IGRT (59.1/59.9 Gy, p = 0.006) and refPlan (60.1 Gy, p = 0.012). Similarly, OA-MRgRT yielded reduced median bladder Dmax compared to conv-IGRT (60.0/60.4 Gy, p = 0.006), and refPlan (61.2 Gy, p = 0.002). Overall, accumulated dose differences were small and did not translate into clinically relevant effects., Conclusion: Deformably accumulated OA-MRgRT using 20x3Gy in PC showed significant but small dosimetric differences comparted to conv-IGRT. Feasibility of a dose accumulation methodology was demonstrated, which may be relevant for evaluating future hypo-fractionated OA-MRgRT approaches., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The author Daniela Thorwarth is an Editor-in-Chief for Physics and Imaging in Radiation Oncology and was not involved in the editorial review or the decision to publish this article. MM and DT report institutional collaborations including financial and non-financial support by Elekta AB, Philips, TheraPanacea, Dr. Sennewald, Brainlab and PTW Freiburg. MM, ACM, CG, DT and DZ acknowledge funding through the German Research Council (DFG), grants no. MU 4603/1-1 (PAK997/1). MM acknowledges funding through the German Research Council (DFG), grants no. ZI 736/2-1. All other authors do not declare financial interests/personal relationships., (© 2024 The Author(s).)

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that can manifest with skin nodules and erythematous plaques. In most cases BPDCN progresses rapidly, causing multiple skin lesions and also affecting internal organs and bone marrow, warranting initiation of systemic therapies or hematopoietic stem cell transplantation (HCT). Although not curative, radiotherapy for isolated lesions might be indicated in case of (imminent) ulceration and large or symptomatic lesions. To this end, doses of 27.0-51.0 Gy have been reported. Here, we present the case of an 80-year-old male with BPDCN with multiple large, nodular, and ulcerating lesions of the thorax, abdomen, and face. Low-dose radiotherapy of 2 × 4.0 Gy was administered to several lesions, which resolved completely within 1 week with only light residual hyperpigmentation of the skin in affected areas and reliably prevented further ulceration. Radiotoxicity was not reported. Therefore, low-dose radiotherapy can be an effective and low-key treatment in selected cases of BPDCN, especially in a palliative setting, with a favorable toxicity profile., (© 2024. The Author(s).)

Background: 5‑Fluoruracil (5-FU) and its oral prodrug capecitabine are mainstays in combined chemoradiotherapy regimens. They are metabolized by dihydropyrimidine dehydrogenase (DPYD). Pathogenic variants of the DPYD gene cause a reduction in DPYD activity, leading to possibly severe toxicities. Therefore, patients receiving 5‑FU-/capecitabine-based chemoradiotherapy should be tested for DPYD variants. However, there are limited clinical data on treatment adjustments and tolerability in patients with decreased DPYP activity receiving combined chemoradiotherapy. Therefore, a retrospective analysis of the toxicity profiles of patients with decreased DPYD activity treated at our center was conducted., Materials and Methods: For all patients receiving 5‑FU-/capecitabine-based chemo(radio)therapy at our department, DPYD activity was routinely tested. Genotyping of four DPYD variants (DPYD*2A, DPYD*13, c.2846A > T, and haplotype B3) was conducted according to the recommendation of the German Society for Hematooncology (DGHO) using TaqMan hydrolysis polymerase chain reaction (PCR; QuantStudy 3, Thermo FisherScientific, Darmstadt). DPYD variants and activity score as well as clinical data (tumor entity, treatment protocol, dose adjustments, and toxicity according to the Common Terminology Criteria for Adverse Events [CTCAE]) were assessed and reported., Results: Of 261 tested patients, 21 exhibited DPYD variants, 18 of whom received chemoradiotherapy. All but one patient was treated for rectal or anal carcinoma. The observed rate of DPYD variants was 8.0%, and heterozygous haplotype B3 was the most common (5.75%). One patient exhibited a homozygous DPYD variant. DPYD activity score was at least 0.5 in heterozygous patients; chemotherapy dose was adjusted accordingly, with an applied dose of 50-75%. CTCAE grade 2 skin toxicity (50%) and grade 3 leukopenia (33.3%) were most common. One patient experienced a transient grade 4 increase in transaminases. All high-grade toxicities were manageable with supportive treatment and transient. No CTCAE grade 5 toxicities related to 5‑FU administration were observed., Conclusion: With dose reduction in heterozygous patients, toxicity was within the range of patients without DPYD variants. Our clinical data suggest that dose-adapted 5‑FU-/capecitabine-chemoradiotherapy regimens can be safely considered in patients with heterozygous clinically relevant DPYD variants, but that the optimal dosage still needs to be determined to avoid both increased toxicity and undertreatment in a curative setting., (© 2024. The Author(s).)

Introduction: The OligoMetastatic Esophagogastric Cancer (OMEC) project aims to provide clinical practice guidelines for the definition, diagnosis, and treatment of esophagogastric oligometastatic disease (OMD)., Methods: Guidelines were developed according to AGREE II and GRADE principles. Guidelines were based on a systematic review (OMEC-1), clinical case discussions (OMEC-2), and a Delphi consensus study (OMEC-3) by 49 European expert centers for esophagogastric cancer. OMEC identified patients for whom the term OMD is considered or could be considered. Disease-free interval (DFI) was defined as the time between primary tumor treatment and detection of OMD., Results: Moderate to high quality of evidence was found (i.e. 1 randomized and 4 non-randomized phase II trials) resulting in moderate recommendations. OMD is considered in esophagogastric cancer patients with 1 organ with ≤ 3 metastases or 1 involved extra-regional lymph node station. In addition, OMD continues to be considered in patients with OMD without progression in number of metastases after systemic therapy. 18 F-FDG PET/CT imaging is recommended for baseline staging and for restaging after systemic therapy when local treatment is considered. For patients with synchronous OMD or metachronous OMD and a DFI ≤ 2 years, recommended treatment consists of systemic therapy followed by restaging to assess suitability for local treatment. For patients with metachronous OMD and DFI > 2 years, upfront local treatment is additionally recommended., Discussion: These multidisciplinary European clinical practice guidelines for the uniform definition, diagnosis and treatment of esophagogastric OMD can be used to standardize inclusion criteria in future clinical trials and to reduce variation in treatment., Competing Interests: Declaration of Competing Interest Dr. van Laarhoven reports a consultant or advisory role: Amphera, Anocca, Astellas, AstraZeneca, Beigene, Boehringer, Daiichy-Sankyo, Dragonfly, MSD, Myeloid, Servier; Research funding, medication supply, and/or other research support: Auristone, Incyte, Merck, ORCA, Servier; Speaker role: Astellas, Beigene, Benecke, BMS, Daiichy-Sankyo, JAAP, Medtalks, Novartis, Springer, Travel Congress Management B.V. Dr. Muijs reports institutional grants from: Elekta, IBA, RaySearch, Siemens, Mirada, Bergoz Instrumentation and Medical Data Works, KWF, all outside the submitted work. Dr. van Hillegersberg has a consulting and advisory role at Intuitive Surgical, Medtronic, Olympus and J&J Ethicon. Dr. de Manzoni reports personal fees from Lilly, outside the submitted work. Dr. Gani reports travel grants from Elekta and departmental research cooperation, outside the submitted work. Dr. Smyth is supported by the NIHR Biomedical Research Centre at Oxford (the views expressed in this Article are those of the authors and not necessarily those of the National Health Service, the NIHR, or the Department of Health) and resports personal fees/grants from: Astra Zeneca, Beigene, BMS, Amal Therapeutics, Amgen, Daiichi Sankyo, Merck, Servier, Novartis, Pfizer, Roche, and Zymeworks, all outside the submitted work. Dr. Haj Mohammad reports consulation fees from: Merck, BMS, Eli Lilly, Astra Zeneca, and research funding from Servier, all outside the submitted work. Dr. Adenis reports grants and personal fees from Bayer, personal fees and non-financial support from MSD, personal fees from: BMS, Novartis, Pierre-Fabre, non-financial support from Servier, grants from Sanofi, all outside the submitted work. Dr. Lordick reports grants from: BMS and Gilead, personal fees from: Amgen, Astellas, Bayer, BMS, Daiichi Sankyo, Eli Lilly, Elsevier, Incyte, Merck, MSD, Roche, Servier, all outside the submitted work. Dr. Slingerland reports an advisory role at BMS and Lilly. Dr. van Berge Henegouwen received researcher-initiated grant from Stryker and is consultant for Alesi Surgical, Johnson and Johnson, Medtronic, BBraun and Viatris. Dr Nilsson reports advisory roles for BMS and Medtronic. Dr. Tabernero reports personal financial interest in form of scientific consultancy role for Array Biopharma, AstraZeneca, Avvinity, Bayer, Boehringer Ingelheim, Chugai, Daiichi Sankyo, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Ikena Oncology, IQVIA, Lilly, Menarini, Merck Serono, Merus, MSD, Mirati, Neophore, Novartis, Orion Biotechnology, Peptomyc, Pfizer, Pierre Fabre, Samsung Bioepis, Sanofi, Seattle Genetics, Servier, Taiho, Tessa Therapeutics and TheraMyc; and also educational collaboration with Imedex, Medscape Education, MJH Life Sciences, PeerView Institute for Medical Education and Physicians Education Resource (PER). Dr. Tabernero declares institutional financial interest in form of financial support for clinical trials or contracted research for Amgen Inc, Array Biopharma Inc, AstraZeneca Pharmaceuticals LP, BeiGene, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Debiopharm International SA, F. Hoffmann-La Roche Ltd, Genentech Inc, HalioDX SAS, Hutchison MediPharma International, Janssen-Cilag SA, MedImmune, Menarini, Merck Health KGAA, Merck Sharp & Dohme, Merus NV, Mirati, Novartis Farmacéutica SA, Pfizer, Pharma Mar, Sanofi Aventis Recherche & Développement, Servier, Taiho Pharma USA Inc, Spanish Association Against Cancer Scientific Foundation and Cancer Research UK. Dr. Nieuwenhuijzen reports advisory/speaker roles from Medtronic and Lilly. All remaining authors have declared no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The use of hypofractionated radiotherapy in prostate cancer has been increasingly evaluated, whereas accumulated evidence demonstrates comparable oncologic outcomes and toxicity rates compared to normofractionated radiotherapy. In this prospective study, we evaluate all patients with intermediate-risk prostate cancer treated with ultrahypofractionated (UHF) MRI-guided radiotherapy on a 1.5 T MR-Linac within our department and report on workflow and feasibility, as well as physician-recorded and patient-reported longitudinal toxicity. A total of 23 patients with intermediate-risk prostate cancer treated on the 1.5 T MR-Linac with a dose of 42.7 Gy in seven fractions (seven MV step-and-shoot IMRT) were evaluated within the MRL-01 study (NCT04172753). The duration of each treatment step, choice of workflow (adapt to shape-ATS or adapt to position-ATP) and technical and/or patient-sided treatment failure were recorded for each fraction and patient. Acute and late toxicity were scored according to RTOG and CTC V4.0, as well as the use of patient-reported questionnaires. The median follow-up was 12.4 months. All patients completed the planned treatment. The mean duration of a treatment session was 38.2 min. In total, 165 radiotherapy fractions were delivered. ATS was performed in 150 fractions, 5 fractions were delivered using ATP, and 10 fractions were delivered using both ATS and ATP workflows. Severe acute bother (G3+) regarding IPS-score was reported in five patients (23%) at the end of radiotherapy. However, this tended to normalize and no G3+ IPS-score was observed later at any point during follow-up. Furthermore, no other severe genitourinary (GU) or gastrointestinal (GI) acute or late toxicity was observed. One-year biochemical-free recurrence survival was 100%. We report the excellent feasibility of UHF MR-guided radiotherapy for intermediate-risk prostate cancer patients and acceptable toxicity rates in our preliminary study. Randomized controlled studies with long-term follow-up are warranted to detect possible advantages over current state-of-the-art RT techniques.

Background and Purpose: MR-guided radiotherapy (MRgRT) online plan adaptation accounts for tumor volume changes, interfraction motion and thus allows daily sparing of relevant organs at risk. Due to the high interfraction variability of bladder and rectum, patients with tumors in the pelvic region may strongly benefit from adaptive MRgRT. Currently, fast automatic annotation of anatomical structures is not available within the online MRgRT workflow. Therefore, the aim of this study was to train and validate a fast, accurate deep learning model for automatic MRI segmentation at the MR-Linac for future implementation in a clinical MRgRT workflow., Materials and Methods: For a total of 47 patients, T2w MRI data were acquired on a 1.5 T MR-Linac (Unity, Elekta) on five different days. Prostate, seminal vesicles, rectum, anal canal, bladder, penile bulb, body and bony structures were manually annotated. These training data consisting of 232 data sets in total was used for the generation of a deep learning based autocontouring model and validated on 20 unseen T2w-MRIs. For quantitative evaluation the validation set was contoured by a radiation oncologist as gold standard contours (GSC) and compared in MATLAB to the automatic contours (AIC). For the evaluation, dice similarity coefficients (DSC), and 95% Hausdorff distances (95% HD), added path length (APL) and surface DSC (sDSC) were calculated in a caudal-cranial window of ± 4 cm with respect to the prostate ends. For qualitative evaluation, five radiation oncologists scored the AIC on the possible usage within an online adaptive workflow as follows: (1) no modifications needed, (2) minor adjustments needed, (3) major adjustments/ multiple minor adjustments needed, (4) not usable., Results: The quantitative evaluation revealed a maximum median 95% HD of 6.9 mm for the rectum and minimum median 95% HD of 2.7 mm for the bladder. Maximal and minimal median DSC were detected for bladder with 0.97 and for penile bulb with 0.73, respectively. Using a tolerance level of 3 mm, the highest and lowest sDSC were determined for rectum (0.94) and anal canal (0.68), respectively. Qualitative evaluation resulted in a mean score of 1.2 for AICs over all organs and patients across all expert ratings. For the different autocontoured structures, the highest mean score of 1.0 was observed for anal canal, sacrum, femur left and right, and pelvis left, whereas for prostate the lowest mean score of 2.0 was detected. In total, 80% of the contours were rated be clinically acceptable, 16% to require minor and 4% major adjustments for online adaptive MRgRT., Conclusion: In this study, an AI-based autocontouring was successfully trained for online adaptive MR-guided radiotherapy on the 1.5 T MR-Linac system. The developed model can automatically generate contours accepted by physicians (80%) or only with the need of minor corrections (16%) for the irradiation of primary prostate on the clinically employed sequences., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [The authors report institutional collaborations with TheraPanacea, Elekta, Philips, Kaiku and PTW Freiburg which provided technical and/or financial support. TheraPanacea developed the proposed model, but were not involved in the analysis and scoring of the testing dataset.], (Copyright © 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.)

Background: Electronic Patient-reported outcome measures (ePROMs) are increasingly used in radiotherapy departments. However, the impact of ePROM integration on patients' perceptions of healthcare providers, particularly in terms of empathy and professionalism, remains unclear. Thus, this study aims to assess the patients' views on healthcare professionals during ePROM-based consultations., Methods: In this randomized trial, radiotherapy patients were enrolled and asked to evaluate video vignettes of consultations between a radiation oncologist and a patient. Two scenarios were shown in random order, one vignette portrayed a paper-chart-based clinic visit, and the other a consultation in which ePROMs were implemented. Established questionnaires such as Physician Compassion Questionnaire (PCQ), Jefferson Patient Perception of Physician Empathy (JPP), Physician Professionalism Questionnaire (PPQ) and Global Consultation Rating Scale (GCRS) were used to rate the healthcare professional. The primary endpoint was physician compassion., Results: Between May and August 2022, 152 patients, predominantly with malignancies of the breast, prostate, and brain participated. Patients rated the physician in ePROM-based consultations with higher mean scores for physician compassion compared to paper chart-based ones (36.4 vs. 34.2, p = 0.029). No negative impact of ePROMs was observed in terms of professionalism, global rating or physician empathy. Despite a shorter duration of the visit and reduced eye contact, 63 % of patients ultimately favored ePROM-based consultations., Conclusion: The ePREFERENCE trial shows that the implementation of ePROMs in clinic visits during radiotherapy treatment positively impacts the patients' perception of the physician's compassion. ePROMs can therefore not only be considered a useful tool to improve workflows but are also broadly accepted by patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Purpose: On-pump coronary artery bypass grafting (CABG) is one of the most common revascularization surgical therapies for coronary artery disease (CAD). However, owing to the use of cardiopulmonary bypass ("on-pump"), the body develops systemic inflammatory response syndrome, which leads to the risk of morbidity and mortality. This study aimed to determine the perioperative outcomes of patients who underwent on-pump CABG surgery using the systemic immune-inflammation index (SII)., Patients and Methods: This single-center retrospective study used secondary data from patients' electronic medical records and medical records archives at the National Cardiovascular Center Harapan Kita, who underwent on-pump CABG from January 2019 to December 2022. A total of 1056 on-pump CABG procedures were performed after exclusion. Lymphocyte, segmental neutrophil, and platelet counts from the preoperative data were used to calculate the SII values. An SII cutoff value of 528.715 × 10 3 /mm 3 divided the patients into two groups., Results: The SII value of 1056 patients were calculated, among which 490 (46%) patients had a preoperative SII value of ≥528.715 × 10 3 /mm 3. Multivariate analysis showed that a high SII significantly prolonged the duration of surgery (OR 1.005, 95% CI 1.003-1.006) and cardiopulmonary bypass (CPB) time (OR 1.007, 95% CI 1.005-1.009). High SII values significantly predicted prolonged mechanical ventilation (OR 6.154, 95% CL 3.938-9.617), intensive care unit (ICU) stay (OR 6.332, 95% CL 4.232-9.474), and hospital stay (OR 3.517, 95% CL 2.711-4.562). Regarding other perioperative outcomes, a high SII significantly predicted the risk of postoperative atrial AF, cardiac arrest, acute myocardial infarction, and mortality., Conclusion: A high preoperative SII value can predict morbidity and mortality in patients undergoing on-pump CABG surgery., Competing Interests: The authors declare no conflicts of interest in this work., (© 2024 Parmana et al.)

Competing Interests: Die Übersicht über die Interessenskonflikte der Autorinnen und Autoren ist im Leitlinienreport veröffentlicht.

Purpose: To assess the robustness of prognostic biomarkers and molecular tumour subtypes developed for patients with head and neck squamous cell carcinoma (HNSCC) on cell-line derived HNSCC xenograft models, and to develop a novel biomarker signature by combining xenograft and patient datasets., Materials and Methods: Mice bearing xenografts (n = 59) of ten HNSCC cell lines and a retrospective, multicentre patient cohort (n = 242) of the German Cancer Consortium-Radiation Oncology Group (DKTK-ROG) were included. All patients received postoperative radiochemotherapy (PORT-C). Gene expression analysis was conducted using GeneChip Human Transcriptome Arrays. Xenografts were stratified based on their molecular subtypes and previously established gene classifiers. The dose to control 50 % of tumours (TCD50) was compared between these groups. Using differential gene expression analyses combining xenograft and patient data, a gene signature was developed to define risk groups for the primary endpoint loco-regional control (LRC)., Results: Tumours of mesenchymal subtype were characterized by a higher TCD50 (xenografts, p < 0.001) and lower LRC (patients, p < 0.001) compared to the other subtypes. Similar to previously published patient data, hypoxia- and radioresistance-related gene signatures were associated with high TCD50 values. A 2-gene signature (FN1, SERPINE1) was developed that was prognostic for TCD50 (xenografts, p < 0.001) and for patient outcome in independent validation (LRC: p = 0.007)., Conclusion: Genetic prognosticators of outcome for patients after PORT-C and subcutaneous xenografts after primary clinically relevant irradiation show similarity. The identified robust 2-gene signature may help to guide patient stratification, after prospective validation. Thus, xenografts remain a valuable resource for translational research towards the development of individualized radiotherapy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Michael Baumann, CEO and Scientific Chair of the German Cancer Research Center (DKFZ, Heidelberg) is responsible for collaborations with a large number of companies and institutions worldwide. In this capacity, he has signed contracts for research funding and/or collaborations, including commercial transfers, with industry and academia on behalf of his institute(s) and staff. He is a member of several supervisory boards, advisory boards and boards of trustees. Michael Baumann confirms that there is no conflict of interest for this paper. In the past 5 years, Dr. Mechthild Krause received funding for her research projects by IBA (2016), Merck KGaA (2014-2018 for preclinical study; 2018-2020 for clinical study), Medipan GmbH (2014-2018). Dr. Mechthild Krause and Dr. Annett Linge are involved in an ongoing publicly funded (German Federal Ministry of Education and Research) project with the companies Medipan (2019-2022), Attomol GmbH (2019-2022), GA Generic Assays GmbH (2019-2022), Gesellschaft für medizinische und wissenschaftliche genetische Analysen (2019-2022), Lipotype GmbH (2019-2022) and PolyAn GmbH (2019-2022). Dr. Krause and Dr. Linge confirm that, to the best of their knowledge, none of the above-mentioned funding sources were involved in the preparation of this paper. The Department of Radiation Oncology Tübingen receives within the frame of research agreements financial and technical support as well as sponsoring for travels and scientific symposia from Elekta AB (Stockholm, Sweden), TheraPanacea (Paris, France), Philips GmbH (Best, The Netherlands); Dr. Sennewald Medizintechnik GmbH (München, Germany), PTW Freiburg (Germany). All other co-authors declare no conflicts of interests., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Background and Purpose: Before quantitative imaging biomarkers (QIBs) acquired with magnetic resonance imaging (MRI) can be used for interventional trials in radiotherapy (RT), technical validation of these QIBs is necessary. The aim of this study was to assess the reproducibility of apparent diffusion coefficient (ADC) values, derived from diffusion-weighted (DW) MRI, in head and neck cancer using a 1.5 T MR-Linac (MRL) by comparison to a 3 T diagnostic scanner (DS)., Material and Methods: DW-MRIs were acquired on MRL and DS for 15 head and neck cancer patients before RT and in week 2 and rigidly registered to the planning computed tomography. Mean ADC values were calculated for submandibular (SG) and parotid (PG) glands as well as target volumes (TV, gross tumor volume and lymph nodes), which were delineated based on computed tomography. Mean absolute ADC differences as well as within-subject coefficient of variation (wCV) and intraclass correlation coefficients (ICCs) were calculated for all volumes of interest., Results: A total of 23 datasets were analyzed. Mean ADC difference (DS-MRL) for SG, PG and TV resulted in 142, 254 and 93·10 -6 mm 2 /s. wCVs/ICCs, comparing MRL and DS, were determined as 13.7 %/0.26, 24.4 %/0.23 and 16.1 %/0.73 for SG, PG and TV, respectively., Conclusion: ADC values, measured on the 1.5 T MRL, showed reasonable reproducibility with an ADC underestimation in contrast to the DS. This ADC shift must be validated in further experiments and considered for future translation of QIB candidates from DS to MRL for response adaptive RT., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Biomarker-based therapies are increasingly used in cancer patients outside clinical trials. Systematic assessment of patient-reported outcomes (PRO) is warranted to take patients' perspectives during biomarker-based therapies into consideration. We assessed the feasibility of an electronic PRO assessment via a smartphone application., Methods: An interdisciplinary expert panel developed a smartphone application based on symptom burden and health-related quality of life (HRQoL) metrics reported in a retrospective analysis of 292 neuro-oncological patients. The app included validated assessments of health-related quality of life (HRQoL), the burden of symptoms, and psychological stress. Feasibility and usability were tested in a pilot study. Semi-structured interviews with patients and health care professionals (HCP) were conducted, transcribed, and analyzed according to Mayring´s qualitative content analysis. Furthermore, we assessed compliance and descriptive data of ePROs., Results: A total of 14 patients have been enrolled, (9 female, 5 male). A total of 4 HCPs, 9 patients, and 1 caregiver were interviewed regarding usability/feasibility. The main advantages were the possibility to complete questionnaires at home and comfortable implementation in daily life. Compliance was high, for example, 82% of the weekly distributed NCCN distress thermometer questionnaires were answered on time, however, with interindividual variability. We observed a median distress score of 5 (range 0-10, 197 results, n = 12, weekly assessed) and a median Global health score of 58.3 according to the EORTC QLQ-C30 instrument (range 16.7-100, 77 results, n = 12, monthly assessed)., Conclusions: This pilot study proved the feasibility and acceptance of the app. We will therefore expand its application during biomarker-guided therapies to enable systematic PRO assessments., Competing Interests: G.T. has served on advisory boards (Bayer, Boehringer Ingelheim, CureVac, Novocure), as a consultant (Bayer, Boehringer Ingelheim, CureVac), as a steering committee member in non-interventional trials (Bayer, Novocure) and financial compensation for all these activities was provided as institutional funding to the University Hospital Tübingen. C.G. is a consultant for Need Inc. A.F. reports honoraria for presentations for BMS, MSD, Novartis, Pierre-Fabre; Travel support and congress participation support from BMS, Pierre-Fabre, Novartis; Advisory Boards from MSD, BMS, Novartis, Pierre-Fabre, Immunocore and institutional funding from BMS Stiftung Immunonkologie, outside the submitted work. The other authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Society for Neuro-Oncology and the European Association of Neuro-Oncology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background and Purpose: Daily online treatment plan adaptation requires a fast workflow and planning process. Current online planning consists of adaptation of a predefined reference plan, which might be suboptimal in cases of large anatomic changes. The aim of this study was to investigate plan quality differences between the current online re-planning approach and a complete re-optimization., Material and Methods: Magnetic resonance linear accelerator reference plans for ten prostate cancer patients were automatically generated using particle swarm optimization (PSO). Adapted plans were created for each fraction using (1) the current re-planning approach and (2) full PSO re-optimization and evaluated overall compliance with institutional dose-volume criteria compared to (3) clinically delivered fractions. Relative volume differences between reference and daily anatomy were assessed for planning target volumes (PTV60, PTV57.6), rectum and bladder and correlated with dose-volume results., Results: The PSO approach showed significantly higher adherence to dose-volume criteria than the reference approach and clinical fractions (p < 0.001). In 74 % of PSO plans at most one criterion failed compared to 56 % in the reference approach and 41 % in clinical plans. A fair correlation between PTV60 D98% and relative bladder volume change was observed for the reference approach. Bladder volume reductions larger than 50 % compared to the reference plan recurrently decreased PTV60 D98% below 56 Gy., Conclusion: Complete re-optimization maintained target coverage and organs at risk sparing even after large anatomic variations. Re-planning based on daily magnetic resonance imaging was sufficient for small variations, while large variations led to decreasing target coverage and organ-at-risk sparing., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The Department of Radiation Oncology Tübingen receives within the frame of research agreements financial and technical support as well as sponsoring for travels and scientific symposia from Elekta AB (Stockholm, Sweden), TheraPanacea (Paris, France), Philips GmbH (Best, The Netherlands); Dr. Sennewald Medizintechnik GmbH (Munich, Germany), PTW (Freiburg, Germany), Siemens (Munich, Germany) and Kaiku Health (Helsinki, Finland)., (© 2024 The Author(s).)

MR-guided radiotherapy is a treatment approach that combines the advantages of magnetic resonance imaging (MRI) with the precision of radiation therapy. This practical review provides an overview of the current state-of-the-art of MR-guided radiotherapy for rectal cancer, including its technical aspects, clinical outcomes, and existing limitations. Even though some studies have demonstrated the feasibility and safety of this treatment modality, challenges remain in terms of patient selection, treatment planning optimization, and long-term follow-up. Despite these issues, MR-guided radiotherapy shows promise as a potentially valuable rectal cancer treatment approach., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht.

Competing Interests: Die Autorinnen/Autoren geben an, dass die Interessenkonflikte im Leitlinienreport dargelegt sind.

Background and Purpose: KRAS is frequently mutated, and the Y-box binding protein 1 (YB-1) is overexpressed in colorectal cancer (CRC). Mutant KRAS (KRAS mut ) stimulates YB-1 through MAPK/RSK and PI3K/AKT, independent of epidermal growth factor receptor (EGFR). The p21-activated kinase (PAK) family is a switch-site upstream of AKT and RSK. The flavonoid compound fisetin inhibits RSK-mediated YB-1 signaling. We sought the most effective molecular targeting approach that interferes with DNA double strand break (DSB) repair and induces radiosensitivity of CRC cells, independent of KRAS mutation status., Materials and Methods: KRAS activity and KRAS mutation were analyzed by Ras-GTP assay and NGS. Effect of dual targeting of RSK and AKT (DT), the effect of fisetin as well as targeting PAK by FRAX486 and EGFR by erlotinib on YB-1 activity was tested by Western blotting after irradiation in vitro and ex vivo. Additionally, the effect of DT and FRAX486 on DSB repair pathways was tested in cells expressing reporter constructs for the DSB repair pathways by flow cytometry analysis. Residual DSBs and clonogenicity were examined by γH2AX- and clonogenic assays, respectively., Results: Erlotinib neither blocked DSB repair nor inhibited YB-1 phosphorylation under KRAS mutation condition in vitro and ex vivo. DT and FRAX486 effectively inhibited YB-1 phosphorylation independent of KRAS mutation status and diminished homologous recombination (HR) and alternative non-homologous end joining (NHEJ) repair. DT and FRAX486 inhibited DSB repair in CaCo2 but not in isogenic KRAS G12V cells. Fisetin inhibited YB-1 phosphorylation, blocked DSB repair and increased radiosensitivity, independent of KRAS mutation status., Conclusion: Combination of fisetin with radiotherapy may improve CRC radiation response, regardless of KRAS mut status., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The utilization of stereotactic body radiation therapy for the treatment of liver metastasis has been widely studied and has demonstrated favorable local control outcomes. However, several predictive factors play a crucial role in the efficacy of stereotactic body radiation therapy, such as the number and size (volume) of metastatic liver lesions, the primary tumor site (histology), molecular biomarkers (e.g., KRAS and TP53 mutation), the use of systemic therapy prior to SBRT, the radiation dose, and the use of advanced technology and organ motion management during SBRT. These prognostic factors need to be considered when clinical trials are designed to evaluate the efficacy of SBRT for liver metastases.

Purpose: Extensive-stage small cell lung cancer (ES-SCLC) carries a dismal prognosis. The benefit of consolidative thoracic radiotherapy (TR) after first-line chemoimmunotherapy with PD-L1 inhibitors in this setting remains unclear. As TR can improve overall survival (OS) after conventional chemotherapy, we retrospectively analyzed OS of an inhouse cohort treated either with TR or with chemoimmunotherapy alone., Methods: A total of 41 patients treated with chemoimmunotherapy with PD-L1 inhibitors (atezolizumab or durvalumab) for ES-SCLC at our hospital since 2019 were analyzed. TR was administered in 10 fractions of 3 Gy. Patient characteristics, number of immunotherapy cycles received, brain irradiation, and presence of hepatic and cerebral metastasis at diagnosis were assessed. Primary endpoint was OS after first diagnosis., Results: Consolidative TR was associated with a significantly longer OS than systemic therapy alone (1-year OS 78.6% and 2‑year OS 37.1% vs. 1‑year OS 39.7% and 2 years not reached, p = 0.019). With regard to radiotherapy indication, survival at 1 year was 88.9% (log-rank p = 0.016) for patients receiving consolidative TR. For patients receiving TR in case of progression, 1‑year survival was 66.7%. Hepatic and cerebral metastasis at first diagnosis had no significant effect on OS., Conclusion: TR was significantly associated with longer OS. The survival benefit of TR was most pronounced for consolidative radiotherapy after initial chemoimmunotherapy compared to TR in case of progression. Although retrospective findings need to be interpreted with caution, in the absence of prospective data, our findings provide a basis for offering consolidative TR in the era of chemoimmunotherapy., (© 2023. The Author(s).)

Purpose: Coronary artery disease (CAD) is the primary cause of mortality in developing countries. Off-pump coronary artery bypass grafting (OPCAB) offers more upside in revascularization by preventing cardiopulmonary bypass trauma and minimizing aortic manipulation. Even though cardiopulmonary bypass is not involved, OPCAB still causes a significant systemic inflammatory response. This study determines the prognostic values of the systemic immune-inflammation index (SII) towards perioperative outcomes in patients who underwent OPCAB surgery., Patients and Methods: This was a single-center retrospective study at the National Cardiovascular Center Harapan Kita, Jakarta, using secondary data from electronic medical records and medical record archives of all patients who underwent OPCAB from January 2019 through December 2021. A total of 418 medical records were obtained, and 47 patients were excluded based on the exclusion criteria. The values of SII were calculated from preoperative laboratory data of segmental neutrophil count, lymphocyte count, and platelet count. Patients were divided into two groups based on the SII cutoff value of 878.056 x 10 3 /mm 3 ., Results: The baseline SII values of 371 patients were calculated, among which 63 (17%) patients had preoperative SII values of ≥878.057 x 10 3 /mm 3 . High SII values were a significant predictor of prolonged ventilation (RR 1.141, 95% CI 1.001-1.301) and prolonged ICU stay (RR 1.218, 95% CI 1.021-1.452) after OPCAB surgery. A positive correlation was observed between SII and hospital length of stay after OPCAB surgery. From the receiver operating characteristic curve analysis, SII predicted prolonged ventilation duration, with an area under the curve of 0.658 (95% CI 0.575-0.741, p = 0.001)., Conclusion: High preoperative SII values are capable of predicting prolonged mechanical ventilation and intensive care unit stay after OPCAB surgery., Competing Interests: The authors declare no conflicts of interest in this work., (© 2023 Parmana et al.)