Currently, no consensus exists regarding the definition of oligometastatic pancreatic ductal adenocarcinoma, its necessary diagnostic measures, and potential treatment approaches. To address these knowledge gaps, the OligoPanc project brought together an interdisciplinary group of experts to establish consensus using a modified Delphi process and clinical vignettes. Participants agreed that the number of metastatic lesions and the number of affected organs are key elements in defining oligometastatic pancreatic ductal adenocarcinoma. Specifically, up to three lesions in a single organ, either the liver or the lung, define oligometastatic pancreatic ductal adenocarcinoma and could be either synchronous or metachronous. Necessary diagnostics include a triple-phase contrast-enhanced CT scan of the chest and abdomen and MRI of the liver with a hepatocyte-specific contrast agent. In unclear cases, [18F]fluorodeoxyglucose-PET CT or MRI can be considered. A multidisciplinary tumour board is essential. Patient-intrinsic factors, including age, do not define oligometastatic disease but should be considered for any treatment decision. Systemic treatment before any local consolidative treatment, including surgery, stereotactic ablative radiotherapy, or other locally ablative techniques, is mandatory. The proposed definition should be incorporated into future trials to improve comparability and enable validation.

Neoadjuvant therapies incorporating immune checkpoint inhibitors (ICIs) have shown promise in locally advanced head and neck squamous cell carcinoma (HNSCC). However, biomarkers for pathological complete response (pCR) remain undefined. In the CheckRad-CD8 trial (NCT03426657), we performed RNA sequencing on pre- and post-treatment biopsies from 77 locally advanced HNSCC patients treated with induction chemoimmunotherapy. Of these, 42 patients achieved pCR, while 35 had residual disease (RD). Differentially expressed genes (DEGs) and pathways were identified using DESeq2 and gene set enrichment analysis. Tumor immune microenvironment analysis, utilizing eight RNAseq deconvolution methods, assessed 266 gene signatures and 38 curated immunotherapy signatures. Baseline intratumoral CD8+ T-cell density, stromal tumor lymphocyte infiltration, and combined PD-L1 proportion score were associated with pCR. Pretreatment analysis identified 830 DEGs between pCR and RD, with T and B-cell-related pathways enriched in pCR samples. Logistic regression models indicated the significance of T and B cells and IFN-gamma signaling in predicting pCR. Furthermore, a new CheckRad-7-gene signature, with an AUC of 0.902 in the training cohort, effectively predicted pCR and survival, serving as a robust biomarker for prognosis and treatment response in HNSCC.

105 Background: The ESOPEC trial showed that perioperative chemotherapy improved survival compared with preoperative chemoradiotherapy in pts with esophageal adenocarcinoma (EAC). Here we report on PRO which was a key secondary endpoint. Methods: Pts with cT1 cN+ cM0 or cT2-4a cNany cM0 EAC were randomized between perioperative chemotherapy with FLOT (5-FU/leucovorin/oxaliplatin/docetaxel) or preoperative chemoradiotherapy with CROSS (41.4Gy/carboplatin/paclitaxel) both plus tumor resection. PRO was measured using the EORTC Quality of Life Questionnaire Core 30 (C30), Oesophageal Cancer Module (OES18) and Chemotherapy-Induced Peripheral Neuropathy Module (CIPN20) at baseline and during treatment and follow-up. The global health status / QOL (GH; C30), physical functioning (PF; C30), fatigue (FA; C30), dyspnoea (DY; C30), eating problems (EP; OES18), and sensory scale (SS; CIPN20) were chosen as primary outcomes. Predefined time points for comparison of PRO between treatment groups were directly before surgery, after discharge from surgery, and 6, 12, 24, and 36 months after start of treatment. Analyses were performed with mixed linear models for repeated measurements. Results: Of 438 randomized patients, 401 (197 FLOT, 204 CROSS) were included in the PRO analysis. Differences between The FLOT and CROSS groups are shown in the table. Before, surgery, GH and PF were higher in the FLOT group, while FA, DY, and EP were less pronounced in the FLOT as compared to CROSS group. At discharge from surgery and at follow-up, no significant differences in GH, PF, FA, DY, and EP were measured. Results in SS were worse in FLOT as compared to CROSS at all timepoints. Conclusions: Patients treated with FLOT as compared to CROSS reported better PRO results following neoadjuvant therapy and before surgery. In contrast, sensory problems were higher in FLOT versus CROSS over the whole treatment trajectory and follow-up. Clinical trial information: NCT02509286 . Adjusted mean difference in points (FLOT minus CROSS)with 95%-CI and two-sided p-value Preoperatively Discharge 6 months 36 months Global health status / QOL* 6.3 (1.1,11.5)p=0.019 0.6 (-4.9,6.1)p=0.83 -4.3 (-9.6,1.0)p=0.11 2.7 (-3.4,8.8)p=0.38 Physical functioning* 7.7 (3.1,12.4)p=0.001 5.3 (-0.6,11.1)p=0.076 -3.1 (-9.0,2.7)p=0.29 2.8 (-3.5,9.1)p=0.39 Fatigue** -8.6 (-14.2,-3.0)p=0.003 -2.7 (-9.1,3.7)p=0.41 5.2 (-1.5,11.8)p=0.13 -4.8 (-12.3,2.6)p=0.20 Dyspnoea** -10.9 (-17.1,-4.7)p<0.001 -1.8 (-10.5,6.8)p=0.68 1.5 (-7.5,10.4)p=0.75 0.7 (-8.9,10.2)p=0.89 Eating problems** -12.7 (-18.9,-6.4)p<0.001 -2.9 (-10.1,4.3)p=0.43 -0.0 (-7.3,7.3)p=1.00 -5.3 (-13.5,3.0)p=0.21 Sensory scale** 14.8 (11.6,18.0)p<0.001 4.8 (1.7,8.0)p=0.003 14.6 (10.7,18.5)p<0.001 7.1 (1.1,13.0)p=0.020 *Higher scores indicate better QOL/function. **Higher scores indicate more symptoms.

INTRODUCTION:Outcome patterns for stereotactic body radiotherapy (SBRT) of bone oligometastases (BoM) especially for older patients are inadequately defined. We aimed to evaluate oncological outcomes and tolerability of SBRT for BoM in older patients. MATERIAL AND METHODS:Patients ≥70 years treated with SBRT for BoM between 2010 and 2024 at 20 European centers were analyzed and compared to patients <70 years. Outcomes included local recurrence (LR)/ freedom from LR (FFLR), progression-free survival (PFS), overall survival (OS), and adverse events. RESULTS:789 patients with 1079 BoM were analyzed. Median age was 68 years (range: 19-91), and 355 patients (45.0%) were ≥70 years. Most common primary tumors were prostate (57.4%), breast (13.8%), and lung cancers (10.5%). LR at 3 years was 9.3% (CI: 6.0-12.8%) in patients <70 years and 11.7% (CI: 7.1-16.8%) in patients ≥70 years (p = 0.39). Grade-3 adverse events occurred in 1.8% of patients <70 years and 1.4% ≥70 years. No grade-4/5 adverse events were observed. Fracture rates were 2.9% for patients <70 years, and 1.8% ≥70 years. A higher metastatic volume was associated with reduced FFLR (Hazard ratio [HR] 1.006; p = 0.02), PFS (HR 1.003; p = 0.05), and OS (HR 1.003; p = 0.04). A better performance status was related to improved PFS (HR 0.98; p < 0.01) and OS (HR 0.96; p < 0.001), while age was not a significant factor. CONCLUSION:This multicenter cohort analysis showed that SBRT of BoM is effective and well tolerated even in older patients. There were no significant differences in outcomes or side effects including fracture rates across patient age groups.

Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) are among those primary liver tumors with the worst prognoses. Due to their biological complexity, the frequently impaired liver function, and the broad spectrum of therapeutic options, these tumors require a consistent multidisciplinary treatment strategy. In this context, the multidisciplinary tumor board (MTB) is not only an organizational instrument but also a medical necessity that is firmly anchored as a standard of care in all relevant international guidelines. For HCC, the therapeutic spectrum of the MTB encompasses curative strategies in early stages-resection, liver transplant, and thermal ablation-as well as locoregional treatments for intermediate stages, particularly transarterial chemoembolization (TACE), radioembolization with 90Yttrium (Y-90), and stereotactic body radiation. The latter has significant advantages for lesions close to vessels or the diaphragm as well as in patients with portal vein thromboses, and it complements the spectrum of interventional options in combination with TACE. In advanced stages, immune checkpoint-based combination therapy-particularly atezolizumab plus bevacizumab (IMbrave150) as well as tremelimumab plus durvalumab (HIMALAYA)-has fundamentally changed systemic first-line therapy and improved median overall survival to up to 19 months. The evidence supporting the importance of the MTB in HCC is convincing: patients discussed in the MTB were diagnosed in earlier stages, received more timely treatment, and had improved 5-year survival rates (up to 71% compared to 59% without MTB presentation). For CCA, in addition to R0 resection as the only curative approach, the integration of molecular diagnostics-particularly next-generation sequencing (NGS)-based profiling for FGFR2, IDH1, and HER2 alterations-is a central task of the MTB. Establishment of the indication for neoadjuvant chemotherapy in tumors with borderline resectability, the coordination of locoregional treatments, and selection for transplant protocols among highly selected patients represent further MTB decisions. In summary, the current evidence indicates that optimal oncological outcomes are only achievable in HCC and CCA via the seamless integration of all relevant disciplines in the MTB. The referral of patients to tertiary centers with established hepatobiliary MTB structures should be a mandatory quality standard.

BACKGROUND AND PURPOSE:Local control rates for pulmonary metastases from head and neck squamous cell carcinoma (HNSCC) treated with stereotactic body radiation therapy (SBRT) vary substantially in the literature, likely in part due to differences in the doses applied. This study, therefore, aims to develop tumor control probability (TCP) models. METHODS:Dose-time modeling of TCP was performed for three key dose descriptors: 3-fraction equivalent dose (3fxED) prescription dose, 3fxED planning target volume (PTV) D95%, and 3fxED PTV D2%. Each dose descriptor was stratified into 4 dose groups using a k-medians clustering algorithm, and the Kaplan-Meier estimator was computed in each group separately to enable time-dependent dose-response modeling. Logistic regression models were fitted using maximum likelihood estimation with model parameters determined separately for 1-year and 2-year local control. RESULTS:This retrospective multicenter analysis included 318 pulmonary metastases from 215 patients. The median 3fxED prescription dose was 45.0 Gy (IQR, 39.2-46.5), corresponding to a biologically effective dose (α/β = 20 Gy) (BED20) of 78.8 Gy (IQR, 64.8-82.5). After a median radiographic follow-up of 13.3 months (IQR, 6.6-32.0), 21 local failures were observed. All models indicated a dose-dependent effect on the local control probability. A local control rate of 95 % was achieved at 1 and 2 years when 3fxED prescription doses and PTV D95% exceeded about 51 Gy (94 Gy BED20), and when PTV D2% reached 66 Gy (139 Gy BED20). CONCLUSION:These TCP models suggest a dose-dependent probability of local control in pulmonary HNSCC metastases treated with SBRT and provide a basis for future clinical assessments in this population.

Whole-breast radiotherapy (WBRT) after breast-conserving surgery (BCS) in older patients can be challenging due to the increased presence of comorbidities, comedication, the presence of a pacemaker or difficulties in traveling to treatment every day. Challenging times, such as the pandemic, can also lead to RT not being performed despite the indication. Very short treatment regimens are therefor of special interest in this population reducing overall treatment time and radiation exposure. TARGIT-E is a phase II trial investigating intraoperative radiotherapy (IORT) during BCS in elderly patients. We report long-term follow-up results of TARGIT-E. Patients with BC (≥ 70 years, cT1-2, cN0, M0) were enrolled at 28 European centers. A single dose of IORT (20 Gy) was given during BCS. Additional postoperative WBRT was applied if risk factors were present in final histopathology. Primary outcome was local recurrence-free rate (RFR) using the Kaplan–Meier-method. Late toxicities were assessed by LENT-SOMA criteria, and cosmetic outcomes were graded using BCCT.core software. In 591 patients (median follow-up 5.4 years) RFR was 97.6

BACKGROUND AND PURPOSE:This study investigates the use of Vision Transformers (ViTs) to predict Freedom from Local Failure (FFLF) in patients with brain metastases using pre-operative MRI scans. The goal is to develop a model that enhances risk stratification and informs personalized treatment strategies. MATERIALS AND METHODS:Within the AURORA retrospective trial, patients (n = 352) who received surgical resection followed by post-operative stereotactic radiotherapy (SRT) were collected from seven hospitals. We trained our ViT for the direct image-to-risk task on T1-CE and FLAIR sequences and combined clinical features along the way. We employed segmentation-guided image modifications, model adaptations, and specialized patient sampling strategies during training. The model was evaluated with five-fold cross-validation and ensemble learning across all validation runs. An external, international test cohort (n = 99) within the dataset was used to assess the generalization capabilities of the model, and saliency maps were generated for explainability analysis. RESULTS:We achieved a competent C-Index score of 0.7982 on the test cohort, surpassing all clinical, CNN-based, and hybrid baselines. Kaplan-Meier analysis showed significant FFLF risk stratification. Saliency maps focusing on the BM core confirmed that model explanations aligned with expert observations. CONCLUSION:Our ViT-based model offers a potential for personalized treatment strategies and follow-up regimens in patients with brain metastases. It provides an alternative to radiomics as a robust, automated tool for clinical workflows, capable of improving patient outcomes through effective risk assessment and stratification.

PURPOSE:The value of stereotactic body radiation therapy (SBRT) in patients with oligometastatic head-and-neck squamous cell carcinoma (HNSCC) remains unclear, as existing evidence is primarily derived from retrospective single-center analyses with small patient cohorts. This study aimed to evaluate the outcomes of pulmonary SBRT in patients with oligometastatic HNSCC and to identify factors associated with survival. METHODS AND MATERIALS:This trinational multicenter cohort study, including 16 centers from Germany, Austria, and Switzerland, retrospectively analyzed patients with oligometastatic HNSCC undergoing SBRT for pulmonary metastases between 2010 and 2023. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival and incidence of local failures. RESULTS:A total of 178 patients with 284 irradiated lung metastases were analyzed. The most common primary HNSCC subsites were oropharyngeal (n = 71), laryngeal (n = 37), and hypopharyngeal (n = 31). Lung metastases were treated with a median biologically effective dose (BEDα/β=10 Gy) of 105 Gy (IQR, 84-113) at the planning target volume periphery. After a median follow-up of 40 months (95% CI, 34-46), the median OS and progression-free survival were 33 months (95% CI, 26-40) and 9 months (95% CI, 7-11), respectively. The 1-year cumulative incidence of local failures was 5.5% (95% CI, 3.2-8.8). One patient (0.6%) developed acute grade 3 dysphagia, and among 146 patients assessed for chronic toxicities, 2 (1.4%) experienced grade 3 events, with no grade 4-5 toxicities. On multivariable analysis, older (>65 years) patients (hazard ratio [HR], 1.59; 95% CI, 1.02-2.49; P = .040) and females (HR, 1.76; 95% CI, 1.04-2.99; P = .035) exhibited worse OS, whereas longer time between HNSCC diagnosis and first SBRT was associated with longer OS (HR, 0.99; 95% CI, 0.99-1.00; P = .045). CONCLUSION:SBRT for pulmonary metastases achieves excellent local control with minimal toxicity in patients with oligometastatic HNSCC. Prospective trials are needed to determine the optimal timing for integrating SBRT with systemic treatment.

Purpose/Objective(s) When designing the ESOPEC trial, the CROSS (C) regimen provided the highest level of evidence of neoadjuvant therapy for both, squamous cell (ESCC) and EAC. During recruitment into ESOPEC, the FLOT(F)-4 trial identified perioperative 5-fluorouracil, leucovorin (L), oxaliplatin (O) and docetaxel (T) as best evidence of chemotherapy. The ESOPEC trial aimed to compare the two protocols exclusively in EAC and hypothesized F to be superior to C. Materials/Methods Included were patients with cM0 EAC staged cT1 N+ or cT2-4a, cN0/+. C was the control arm with 41.4 Gy in 23 fractions and 5 weekly simultaneous doses of carboplatin (2 mg/ml/min AUC) and paclitaxel [(50 mg/m²); CP]. GTV and PTV were defined as described by Matzinger et al. (doi: 10.1016/j.radonc.2009.03.018). F was the experimental arm with 5-fluorouracil 2600 mg/m² (24 hours), d1 L 200 mg/m², d1 O 85 mg/m², d1 T 50mg/m2, d1 every two weeks (q2w); 4 neoadjuvant cycles (8 weeks) prior to surgery and 4 adjuvant cycles (8 weeks) postoperatively. Esophagectomy was done 4-6 weeks after neoadjuvant therapies. Primary endpoint was overall survival (OS), secondary endpoints were progression free survival (PFS), ypTNM stage, tumor regression grading, recurrence free survival (RFS) in patients with R0/R1 resection, site of tumor recurrence, postoperative complications, adverse events, and quality of life. Sample size calculation was based on 1-sided significance level of 2.5% and 90% power assuming a hazard ratio (HR) of 0.645 with respect to OS, and required 218 death events (438 patients). Prospectively documented chemoradiotherapy specific variables consisted in administered percentage of planned chemo- and radiotherapy, adherence to target volume definitions, doses to organs at risk, specifically heart and lungs. Results From 2/16 to 4/20, 438 patients were randomized to C (217) and F (221), intention-to-treat population (ITT). Characteristics were well balanced with mean age of 63 years, 89.3% males, 73.9% cT3, 6.7% cT4, 79.7% cN+. Neoadjuvant treatment was started in 90.3% (196) vs 93.7% (207) in C vs F (per-protocol-population (PP)). In PP, full RT dose was given in 98.0% (192); 75.0% (147), 18.9% (37) and 6.1% (12) had 5, 4 or <4 cycles of CP. In ITT, surgery rates were C 82.9% (180) vs F 86.4% (191). In 371 patients with surgery, local pCR rates were 13.3% (C) vs 18.3% (F), and near CR rates 39.4% (C) vs 25.1% (F). In 368 patients with R0/R1 resection, 3-year RFS after surgery was 36.5% (C) and 52.8% (F), median RFS was 17 (C) vs 43 (F) months (HR 0.68 [0.51 – 0.90]; p = 0.0076). Postoperative morbidity was comparable. In ITT, 3-year-OS was 50.7% (C) and 57.4% (F), and median OS was 37 (C) vs 66 (F) months (HR 0.70 [0.53 – 0.92]; p = 0.012). Conclusion Both C and F were well tolerated. OS was superior after F vs C, and F should be preferred over C. Posthoc limitations of C were: baseline FDG-PET/CT not mandatory and absence of additive immunotherapy.

Purpose/Objective(s) To develop expert recommendations for multiparametric dose prescriptions of SBRT according to ICRU report 91 to harmonize current SBRT practice and clinical trial design. Materials/Methods Based on results of a working group literature summary a 2-tier Delphi-consensus process of 24 physician and physics experts from 3 European countries was conducted. Degree of consensus was predefined for overarching (OA) and organ specific (OS) statements (≥80%, 60-79%, <60% for high, intermediate and poor consensus). Post first round, statements were refined in a live discussion with 125 participants for the second round of the Delphi process. Results Experts consented on a total of 14 OA and 17 OS statements of SBRT of primary and secondary lung as well as liver, pancreas, adrenal and kidney tumors. Degree of consent was ≥80% in 79% and 41% of OA and OS statements, respectively, with higher consensus for lung compared to upper abdomen. In round 2, degree of consent ≥80% increased to 100% for OA and 88% in OS statements. No consensus was reached for dose escalation of liver metastases after chemotherapy (47%) and single fraction SBRT for kidney primaries (13%). In round 2, no statements had 60-79% consensus. Conclusion In 29 of 31 statements a high consensus was achieved after a 2-tier Delphi process, and 1 statement (kidney) was clearly refused. The Delphi process was able to achieve a high degree of consensus for dose prescription of SBRT. In summary, clear recommendations for both OA and OS could be defined. This contributes significantly to harmonization and for the design of clinical trials in SBRT. Specific exemplary cases will be deducted from the statements in the next step.

To develop expert consensus statements on multiparametric dose prescriptions for stereotactic body radiotherapy (SBRT) aligning with ICRU report 91. These statements serve as a foundational step towards harmonizing current SBRT practices and refining dose prescription and documentation requirements for clinical trial designs. Based on the results of a literature review by the working group, a two-tier Delphi consensus process was conducted among 24 physicians and physics experts from three European countries. The degree of consensus was predefined for overarching (OA) and organ-specific (OS) statements (≥ 80