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Purpose Meningioma is a common type of benign tumor that can be managed in several ways, ranging from close observation, surgical resection, and various types of radiation. We present here results from a 10 year experience treating meningiomas with a hypofractionated approach. Materials and methods To define the rate of tumor control and factors associated with the relief of symptoms and radiation-related complications after radiosurgery and hypofractionated radiosurgery for patients with imaging-defined intracranial meningiomas. We reviewed the charts of 48 patients treated with stereotactic radiosurgery (SRS) or hypofractionated stereotactic radiotherapy (SRT) from 2002 to 2018. A total of 37 (82%) patients had WHO Grade 1 disease, and 11 (22%) had Grade 2. Outcomes that were analyzed included local control rates and the rate and grade of any reported toxicity. Results Only 36 patients with 38 lesions, who underwent the follow-up regime, were enrolled in the retrospective analysis. The follow-up mean was 40 months (12–120 months). 25/34 patients had surgery before the radiotherapy. Sixteen underwent SRS with a median dose of 13, 5, and 20 received hypofractionated SBRT with a median dose of 26.9 (22-45 Gy) in median six fractions (5–13 fractions). Local control at 2 and 5 years for all patients was 90 and 70%, respectively. No patient suffered from toxicity > 2 CTC. 21/36 patients showed stable disease, while 8/36 patients showed partial Remission. 7/36 developed recurrent meningioma (five in-field), only one patient with grade 1 meningioma, in a median of 22 months (13–48 months). Conclusion SFRT was superior to SRS for local control in our analysis of Grade I meningiomas. This might be due to a tendency for higher EQD2 in the PTV with SFRT compared to SRS, which was reduced to avoid brain necrosis in large PTVs. Therefore, SFRT appears preferable for typical meningioma PTVs.

BackgroundMany automatic approaches to brain tumor segmentation employ multiple magnetic resonance imaging (MRI) sequences. The goal of this project was to compare different combinations of input sequences to determine which MRI sequences are needed for effective automated brain metastasis (BM) segmentation.MethodsWe analyzed preoperative imaging (T1-weighted sequence ± contrast-enhancement (T1/T1-CE), T2-weighted sequence (T2), and T2 fluid-attenuated inversion recovery (T2-FLAIR) sequence) from 333 patients with BMs from six centers. A baseline 3D U-Net with all four sequences and six U-Nets with plausible sequence combinations (T1-CE, T1, T2-FLAIR, T1-CE+T2-FLAIR, T1-CE+T1+T2-FLAIR, T1-CE+T1) were trained on 239 patients from two centers and subsequently tested on an external cohort of 94 patients from four centers.ResultsThe model based on T1-CE alone achieved the best segmentation performance for BM segmentation with a median Dice similarity coefficient (DSC) of 0.96. Models trained without T1-CE performed worse (T1-only: DSC = 0.70 and T2-FLAIR-only: DSC = 0.72). For edema segmentation, models that included both T1-CE and T2-FLAIR performed best (DSC = 0.93), while the remaining four models without simultaneous inclusion of these both sequences reached a median DSC of 0.81-0.89.ConclusionsA T1-CE-only protocol suffices for the segmentation of BMs. The combination of T1-CE and T2-FLAIR is important for edema segmentation. Missing either T1-CE or T2-FLAIR decreases performance. These findings may improve imaging routines by omitting unnecessary sequences, thus allowing for faster procedures in daily clinical practice while enabling optimal neural network-based target definitions.

Purpose We aim to recapitulate the rapid development of head and neck radiotherapy in the context of otorhinolaryngology (ORL) medicine starting 125 years ago. This is put into context with the unsuccessful treatment of the laryngeal cancer (LC) of the German emperor Frederick III and its historical consequences. Methods The three-step process consisted in the analysis of (1) historical sources of the development of ORL radiotherapy from the discovery of x‑rays and radioactivity until World War I, (2) course and treatment of Frederick’s III LC, (3) political context with a special focus on the escalation towards World War I. Pertinent historical illustrations of technical developments of radiotherapy were summarized in a video. Results ORL radiotherapy initiated on 03 February 1896, only 65 days after the discovery of X‑rays. By 1914, organ-sparing LC radiotherapy was established with a predominance of curietherapy over roentgentherapy. Correct diagnosis of Frederick III’s primarily radiocurable cT1a glottic LC was delayed by one year, which resulted in advancement to a fatal pT4 pN1 Mx tumour stage. Historically, his successor, William II, was assumed to have contributed to the causes of World War I. Conclusion ORL radiotherapy came only eight years late to treat Frederick III who might have impeded World War I. This illustrates the potential impact of modern curative radiotherapy on the future course of public life beyond the personal fate of the patient himself.

Supplementary Figures 1-7 from Pancreatic Stellate Cells Radioprotect Pancreatic Cancer Cells through β1-Integrin Signaling

Background We used 68Ga PSMA PET/CT in the current investigation to assess the metabolic response and local control of metastasis in patients with oligometastatic prostate cancer receiving SBRT. Materials and procedures We performed a retrospective evaluation of the medical data of all patients with oligometastatic prostate cancer who underwent stereotactic body radiation therapy (SBRT) between 2017 and 2021. Our analysis only included medical records of patients who had SBRT for oligometastatic prostate cancer and had pre and post-SBRT 68Ga PSMA PET/CT images. Patient-related (age), disease-related (Gleason score, location of metastases), and treatment-related (factors and outcomes) data were collected from the medical files. Results A total of 17 patients (28 lesions) with a median age of 69 years were included in the research. A median follow-up of 16.6 months was used (range 6–36 months). The median follow-up period for 68 Ga PSMA PET/CT was 8 months (the range was 5–24 months). The median pre-treatment PSA level was 1.7 ng/mL (range 0.39–18.3 ng/mL) compared to the post-treatment PSA nadir of 0.05 ng/mL (0.02–4.57). During the follow-up period, local control was 96%, and there was a link between PSMA avidity on PET. In the treated lesions, there were no recurrences. During follow-up, none of the patients experienced toxicities of grade 3 or above. Conclusions SBRT is a highly successful and safe way of treating patients with oligometastatic prostate cancer. Additional research is needed to examine 68Ga PSMA PET/CT to assess further for demarcation and follow-up.

Stereotactic radiotherapy is a standard treatment option for patients with brain metastases. The planning target volume is based on gross tumor volume (GTV) segmentation. The aim of this work is to develop and validate a neural network for automatic GTV segmentation to accelerate clinical daily routine practice and minimize interobserver variability.We analyzed MRIs (T1-weighted sequence ± contrast-enhancement, T2-weighted sequence, and FLAIR sequence) from 348 patients with at least one brain metastasis from different cancer primaries treated in six centers. To generate reference segmentations, all GTVs and the FLAIR hyperintense edematous regions were segmented manually. A 3D-U-Net was trained on a cohort of 260 patients from two centers to segment the GTV and the surrounding FLAIR hyperintense region. During training varying degrees of data augmentation were applied. Model validation was performed using an independent international multicenter test cohort (n = 88) including four centers.Our proposed U-Net reached a mean overall Dice similarity coefficient (DSC) of 0.92 ± 0.08 and a mean individual metastasis-wise DSC of 0.89 ± 0.11 in the external test cohort for GTV segmentation. Data augmentation improved the segmentation performance significantly. Detection of brain metastases was effective with a mean F1-Score of 0.93 ± 0.16. The model performance was stable independent of the center (p = 0.3). There was no correlation between metastasis volume and DSC (Pearson correlation coefficient 0.07).Reliable automated segmentation of brain metastases with neural networks is possible and may support radiotherapy planning by providing more objective GTV definitions.

Background and purpose ALBI and IBI are new scores to evaluate the liver function in patients with hepatocellular carcinoma (HCC). The purpose of this study was to evaluate the prognostic abilities of those scores in patients treated with interstitial brachytherapy (iBT). Materials and methods 190 patients treated with iBT between 01.01.2006 and 01.01.2018 were included in this study. The clinical target dose was 15 Gy. The patients were all in Child–Pugh stadium A or B and across the Barcelona Clinic Liver Cancer (BCLC) Stages 0–C. Retrospectively ALBI and IBI were calculated pre- and post-therapeutic until 6 months after iBT. Hazards ratios were calculated, and p values corrected using the false discovery rate according to Benjamini and Hochberg. Results The median overall survival was 23.5 months (CI 19–28.5 months), and the median progression-free survival was 7.5 months (CI 6–9 months). Elevated ALBI showed a significantly higher risk to die with a hazard ratio (HR) of 2.010 (ALBI 2 vs. 1) and 4082 (ALBI 3 vs. 1), respectively. The IBI did also show a higher risk with an HR of 1.816 (IBI 1 vs. 0) and 4608 (IBI 2 vs. 0), respectively. Even 3 months after therapy elevated ALBI and IBI showed poor overall survival. Concerning progression-free survival, ALBI and IBI could not provide any relevant additional information. Conclusion ALBI and IBI are useful tools to predict the overall survival in patients treated with iBT and might be helpful to assign the patients to the appropriate therapy.

Purpose Oligometastatic prostate cancer is heavily investigated, and conventionally fractionated elective nodal treatment appears to increase biochemical relapse-free (bRFS) survival. The novelty of this report is to present elective nodal radiotherapy (ENRT) with simultaneous integrated boost with stereotactic (SBRT) or hypofractionated radiotherapy (HoFRT) for tolerance and for bRFS which we compared with SBRT of the involved field (IF) only. Materials and methods Patients between 2018 and 2021 with and oligometastatic prostate cancer treated with SBRT or hypofractionation were eligible. A radiobiologically calculated simultaneous integrated boost approach enabled to encompass elective nodal radiotherapy (ENRT) with high doses to PSMA-positive nodes. A second group had only involved field (IF) nodal SBRT. Results A total of 44 patients with 80 lesions of initially intermediate- (52%) or high-risk (48%) D’Amico omPC were treated with SBRT to all visible PSMA-PET/CT lesions and 100% of the treated lesions were locally controlled after a median follow-up was 18 months (range 3–42 months). Most lesions (56/80; 70%) were nodal and the remainder osseous. Median bPFS was 16 months and ADT-free bPFS 18 months. ENRT (31 patients) versus IF (13 patients) prevented regional relapse more successfully. At univariate analysis, both initial PSA and length of the interval between primary diagnosis and biochemical failure were significant for biochemical control. Treatment was well tolerated and only two patients had toxicity ≥ grade 3 (1 GU and 1 GI, each). Discussion/conclusion SBRT and hypofractionated radiotherapy at curative doses with ENRT was more effective to delay ADT than IF, controlled all treated lesions and was well tolerated.

Summary Background With increasingly precise radiotherapy and advanced medical imaging, the concept of radiotherapy target volume planning might be redefined with the aim of improving outcomes. We aimed to investigate whether target volume reduction is feasible and effective compared with conventional planning in the context of radical chemoradiotherapy for patients with locally advanced non-small-cell lung cancer. Methods We did a multicentre, open-label, randomised, controlled trial (PET-Plan; ARO-2009-09) in 24 centres in Austria, Germany, and Switzerland. Previously untreated patients (aged older than 18 years) with inoperable locally advanced non-small-cell lung cancer suitable for chemoradiotherapy and an Eastern Cooperative Oncology Group performance status of less than 3 were included. Undergoing 18F-fluorodeoxyglucose (18F-FDG) PET and CT for treatment planning, patients were randomly assigned (1:1) using a random number generator and block sizes between four and six to target volume delineation informed by 18F-FDG PET and CT plus elective nodal irradiation (conventional target group) or target volumes informed by PET alone (18F-FDG PET-based target group). Randomisation was stratified by centre and Union for International Cancer Control stage. In both groups, dose-escalated radiotherapy (60–74 Gy, 2 Gy per fraction) was planned to the respective target volumes and applied with concurrent platinum-based chemotherapy. The primary endpoint was time to locoregional progression from randomisation with the objective to test non-inferiority of 18F-FDG PET-based planning with a prespecified hazard ratio (HR) margin of 1·25. The per-protocol set was included in the primary analysis. The safety set included all patients receiving any study-specific treatment. Patients and study staff were not masked to treatment assignment. This study is registered with ClinicalTrials.gov , NCT00697333 . Findings From May 13, 2009, to Dec 5, 2016, 205 of 311 recruited patients were randomly assigned to the conventional target group (n=99) or the 18F-FDG PET-based target group (n=106; the intention-to-treat set), and 172 patients were treated per protocol (84 patients in the conventional target group and 88 in the 18F-FDG PET-based target group). At a median follow-up of 29 months (IQR 9–54), the risk of locoregional progression in the 18F-FDG PET-based target group was non-inferior to, and in fact lower than, that in the conventional target group in the per-protocol set (14% [95% CI 5–21] vs 29% [17–38] at 1 year; HR 0·57 [95% CI 0·30–1·06]). The risk of locoregional progression in the 18F-FDG PET-based target group was also non-inferior to that in the conventional target group in the intention-to-treat set (17% [95% CI 9–24] vs 30% [20–39] at 1 year; HR 0·64 [95% CI 0·37–1·10]). The most common acute grade 3 or worse toxicity was oesophagitis or dysphagia (16 [16%] of 99 patients in the conventional target group vs 17 [16%] of 105 patients in the 18F-FDG PET-based target group); the most common late toxicities were lung-related (12 [12%] vs 11 [10%]). 20 deaths potentially related to study treatment were reported (seven vs 13). Interpretation 18F-FDG PET-based planning could potentially improve local control and does not seem to increase toxicity in patients with chemoradiotherapy-treated locally advanced non-small-cell lung cancer. Imaging-based target volume reduction in this setting is, therefore, feasible, and could potentially be considered standard of care. The procedures established might also support imaging-based target volume reduction concepts for other tumours. Funding German Cancer Aid (Deutsche Krebshilfe).

PurposeThe first aim of the trial is to study feasibility of combined programmed death protein ligand 1/cytotoxic T-lymphocyte-associated protein 4 inhibition concomitant to radiotherapy. In addition, efficacy of the entire treatment scheme consisting of induction chemoimmunotherapy followed by chemotherapy-free radioimmunotherapy (RIT) after intratumoral CD8 +immune cell-based patient selection will be analyzed.MethodsPatients with stage III–IVB head and neck squamous cell carcinoma were eligible for this multicenter phase II trial. Treatment consisted of a single cycle of cisplatin 30 mg/m² days 1–3, docetaxel 75 mg/m² day 1, durvalumab 1500 mg fix dose day 5 and tremelimumab 75 mg fix dose day 5. Patients with increased intratumoral CD8 +immune cell density or pathological complete response (pCR) in the rebiopsy entered RIT up to a total dose of 70 Gy. Patients received further three cycles of durvalumab/tremelimumab followed by eight cycles of durvalumab mono (every 4 weeks). The intended treatment for patients not meeting these criteria was standard radiochemotherapy outside the trial. Primary endpoint was a feasibility rate of patients entering RIT to receive treatment until at least cycle 6 of immunotherapy of ≥80%.ResultsBetween September 2018 and May 2020, 80 patients were enrolled (one excluded). Out of these, 23 patients had human papilloma virus (HPV)-positive oropharyngeal cancer. Median follow-up was 17.2 months. After induction chemoimmunotherapy 41 patients had pCR and 31 had increased intratumoral CD8 +immune cells. Of 60 patients entering RIT (primary endpoint cohort), 10 experienced imiting toxic (mainly hepatitis) and four discontinued for other reasons, resulting in a feasibility rate of 82%. The RIT cohort (n=60) had a progression-free survival (PFS) rate at one and 2 years of 78% and 72%, respectively, and an overall survival rate at one and 2 years of 90% and 84%, respectively. Patients with HPV-positive oropharyngeal cancers had greater benefit from RIT with a 2-year PFS rate of 94% compared with 64% for HPV-negative oropharyngeal cancers and other locations. In the entire study cohort (n=79) the 2-year PFS rate was 68% (91% for HPV-positive oropharynx vs 59% for others). Toxicity grade 3–4 mainly consisted of dysphagia (53%), leukopenia (52%) and infections (32%).ConclusionsThe trial met the primary endpoint feasibility of RIT. Induction chemo-immunotherapy followed by chemotherapy-free RIT after intratumoral CD8 +immune cell-based patient selection has promising PFS.Trial registration numberThe trial was registered with ClinicalTrials.gov (identifier: NCT03426657). The trial was conducted as investigator-sponsored trial (IST)., publishedVersion

Definition of gross tumor volume (GTV) in hepatocellular carcinoma (HCC) requires dedicated imaging in multiple contrast medium phases. The aim of this study was to evaluate the interobserver agreement (IOA) in gross tumor delineation of HCC in a multicenter panel. The analysis was performed within the “Stereotactic Radiotherapy” working group of the German Society for Radiation Oncology (DEGRO). The GTVs of three anonymized HCC cases were delineated by 16 physicians from nine centers using multiphasic CT scans. In the first case the tumor was well defined. The second patient had multifocal HCC (one conglomerate and one peripheral tumor) and was previously treated with transarterial chemoembolization (TACE). The peripheral lesion was adjacent to the previous TACE site. The last patient had an extensive HCC with a portal vein thrombosis (PVT) and an inhomogeneous liver parenchyma due to cirrhosis. The IOA was evaluated according to Landis and Koch. The IOA for the first case was excellent (kappa: 0.85); for the second case moderate (kappa: 0.48) for the peripheral tumor and substantial (kappa: 0.73) for the conglomerate. In the case of the peripheral tumor the inconsistency is most likely explained by the necrotic tumor cavity after TACE caudal to the viable tumor. In the last case the IOA was fair, with a kappa of 0.34, with significant heterogeneity concerning the borders of the tumor and the PVT. The IOA was very good among the cases were the tumor was well defined. In complex cases, where the tumor did not show the typical characteristics, or in cases with Lipiodol (Guerbet, Paris, France) deposits, IOA agreement was compromised.

Background The intent of this pooled analysis as part of the German society for radiation oncology (DEGRO) stereotactic body radiotherapy (SBRT) initiative was to analyze the patterns of care of SBRT for liver oligometastases and to derive factors influencing treated metastases control and overall survival in a large patient cohort. Methods From 17 German and Swiss centers, data on all patients treated for liver oligometastases with SBRT since its introduction in 1997 has been collected and entered into a centralized database. In addition to patient and tumor characteristics, data on immobilization, image guidance and motion management as well as dose prescription and fractionation has been gathered. Besides dose response and survival statistics, time trends of the aforementioned variables have been investigated. Results In total, 474 patients with 623 liver oligometastases (median 1 lesion/patient; range 1–4) have been collected from 1997 until 2015. Predominant histologies were colorectal cancer (n = 213 pts.; 300 lesions) and breast cancer (n = 57; 81 lesions). All centers employed an SBRT specific setup. Initially, stereotactic coordinates and CT simulation were used for treatment set-up (55%), but eventually were replaced by CBCT guidance (28%) or more recently robotic tracking (17%). High variance in fraction (fx) number (median 1 fx; range 1–13) and dose per fraction (median: 18.5 Gy; range 3–37.5 Gy) was observed, although median BED remained consistently high after an initial learning curve. Median follow-up time was 15 months; median overall survival after SBRT was 24 months. One- and 2-year treated metastases control rate of treated lesions was 77% and 64%; if maximum isocenter biological equivalent dose (BED) was greater than 150 Gy EQD2Gy, it increased to 83% and 70%, respectively. Besides radiation dose colorectal and breast histology and motion management methods were associated with improved treated metastases control. Conclusion After an initial learning curve with regards to total cumulative doses, consistently high biologically effective doses have been employed translating into high local tumor control at 1 and 2 years. The true impact of histology and motion management method on treated metastases control deserve deeper analysis. Overall survival is mainly influenced by histology and metastatic tumor burden.

Cholangiokarzinome (CCA) stellen ein komplexes Krankheitsbild dar, bei dem eine enge interdisziplinare Kooperation unerlasslich ist. Es erfolgten eine selektive Literaturrecherche sowie eine Darstellung der eigenen Erfahrungen in der Therapie von lokalen CCA. Sofern CCA auf die Gallenwege und/oder die Leber beschrankt sind, ist die chirurgische Resektion die Therapie der Wahl. Allerdings ist dies nur in 30–40 % der Falle moglich. Neoadjuvante Therapien spielen bei resektablen Befunden bisher keine Rolle. Dagegen kann bei lokaler Inoperabilitat eine Chemo- und/oder Radiotherapie in Einzelfallen zu einer sekundaren Resektabilitat fuhren. Nach R0-Resektion ist der Lymphknotenstatus einer der wichtigsten Prognosefaktoren. So liegen bei perihilaren CCA die Funfjahresuberlebensraten bei negativen Lymphknoten bei 40–60 %, bei intrahepatischen CCA zwischen 30 % und 40 %. Lymphknotenmetastasen verschlechtert die Prognose deutlich (Funfjahresuberleben

Das hepatozellulare Karzinom (HCC) ist eine haufige Tumorerkrankung mit zunehmender Inzidenz und einer schlechten Prognose. Bei der Therapieentscheidung mussen zahlreiche Faktoren, wie z. B. Grose und Anzahl der Tumoren, die Leberfunktion, die Folgen einer portalen Hypertension oder Begleiterkrankungen berucksichtigt werden. Dies spiegelt sich in der Barcelona Clinic Liver Cancer (BCLC) -Klassifikation wieder. Als kurative Therapien fur das fruhe, lokalisierte Stadium gelten die Resektion, Radiofrequenzthermoablation (RFTA) und Lebertransplantation. Im intermediaren Stadium kommt die transarterielle Chemoembolisation (TACE), seltener eine selektive interne Radiotherapie (SIRT) oder – als off-label – eine stereotaktische Korper-Radiotherapie (SBRT) zum Einsatz. Sorafenib steht als einzige systemische Therapie im fortgeschrittenen Stadium zur Verfugung. Alternative Behandlungsmethoden, wie z. B. immunologische Therapieansatze, werden derzeit untersucht.

Introduction Stereotactic body radiation therapy (SBRT) is applied in the oligometastatic setting to treat liver metastases. However, factors influencing tumor control probability (TCP) other than radiation dose have not been thoroughly investigated. Here we set out to investigate such factors with a focus on the influence of histology and chemotherapy prior to SBRT using a large multi-center database from the German Society of Radiation Oncology. Methods 452 SBRT treatments in 363 patients were analyzed after collection of patient, tumor and treatment data in a multi-center database. Histology was considered through random effects in semi-parametric and parametric frailty models. Dose prescriptions were parametrized by conversion to the maximum biologically effective dose using alpha/beta of 10Gy (BED max ). Results After adjusting for histology, BED max was the strongest predictor of TCP. Larger PTV volumes, chemotherapy prior to SBRT and simple motion management techniques predicted significantly lower TCP. The model predicted a BED of 209±67Gy 10 necessary for 90% TCP at 2years with no prior chemotherapy, but 286±78Gy 10 when chemotherapy had been given. Breast cancer metastases were significantly more responsive to SBRT compared to other histologies with 90% TCP at 2years achievable with BED max of 157±80Gy 10 or 80±62Gy 10 with and without prior chemotherapy, respectively. Conclusions Besides dose, histology and pretreatment chemotherapy were important factors influencing local TCP in this large cohort of liver metastases. After adjusting for prior chemotherapy, our data add to the emerging evidence that breast cancer metastases do respond better to hypofractionated SBRT compared to other histologies.

Pancreatic cancer (PC) predominantly metastasizes to liver, lung, and peritoneum. Metastatic disease correlates with SMAD4 status. Musculoskeletal metastases (MSM) are rare in pancreatic cancer. The role of radiation therapy (RT) in patients with musculoskeletal metastases is not clear. We present a case of a woman with musculoskeletal metastases of PC evolving 4 years after Whipple’s procedure and adjuvant therapy. She was treated with RT for 7 MSM. Radiation dose was 15–45 Gy, delivered in doses of 2.5–5 Gy per fraction. SMAD4 status was examined by immunohistochemistry. Furthermore we undertook a review of the literature to examine the value of RT in musculoskeletal metastasis of PC. In the presented patient we treated 7 MSM of SMAD4-mutant PC with RT. RT achieved local control in 4 of the 7 MSM. At the resection margin of one MSM recurrent tumor was observed after RT. The status of one MSM was unknown and one MSM showed local progression. Follow-up revealed progression of pain in 1 of the 7 MSM. Except of hyperpigmentation no side effects occurred. There was no dose–correlation effect on tumor control observed. A review of the literature showed that a musculoskeletotrophic phenotype of metastases is rare in PC. MSM of PC are rapidly increasing soft tissue masses causing pain and loss of anatomical function. RT as a treatment option for musculoskeletal metastasis is described in the current literature in only 2 cases. Radiotherapy aims to achieve local control, pain relief, and to maintain anatomical function. Radiotherapy is an effective and well-tolerated approach for multiple musculoskeletal metastases of PC.

Background In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging. Patients and methods Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS). Results The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48 % (A) and 52 % (B, P = 0.81) and (y)pN0 was 30 % (A) vs. 39 % (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79). Conclusion This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543. Electronic supplementary material The online version of this article (doi: 10.1007/s00066-014-0737-7) contains supplementary material, which is available to authorized users.

This report of the Working Group on Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) aims to provide a practical guideline for safe and effective stereotactic body radiotherapy (SBRT) of liver tumors.The literature on the clinical evidence of SBRT for both primary liver tumors and liver metastases was reviewed and analyzed focusing on both physical requirements and special biological characteristics.Recommendations were developed for patient selection, imaging, planning, treatment delivery, motion management, dose reporting, and follow-up. Radiation dose constraints to critical organs at risk are provided.SBRT is a well-established treatment option for primary and secondary liver tumors associated with low morbidity.

TPS470 Background: Tumor Treating Fields (TTFields) are a non-invasive, regional antimitotic treatment modality, which has been approved for the treatment of glioblastoma by the FDA. TTFields predominantly act by disrupting the formation of the mitotic spindle during metaphase. TTFields were effective in multiple preclinical models of hepatocellular carcinoma (HCC), leading to a significant increase in cell death. The Phase 2 HEPANOVA study is the first trial testing TTFields in HCC patients, and is designed to test the safety and efficacy of adding TTFields to sorafenib in advanced HCC. Methods: Patients (N = 25) with unresectable HCC who are not amenable to any local treatment will be enrolled in this prospective, single-arm study. The study enrolls patients with ECOG score of 0-2 and Barcelona clinic liver cancer (BCLC) stage 0-C. Patients must have a measurable disease per RECIST Criteria. Having implanted electronic devices in the torso is exclusionary. Sorafenib will be administered at standard dose (400 mg twice daily). TTFields (150 kHz) will be delivered for 18 hours/day until local disease progression per RECIST Criteria. Clinical follow up will be performed q4w, and a CT/MRI scan q12w. Following disease progression in the liver, patients will discontinue TTFields and be followed monthly for survival. Overall response rate will be the primary endpoint and in-field control rate, progression-free survival rate at 12 month (PFS12), OS rate at 1 year and toxicity will all be secondary endpoints. Sample size was calculated using an Exact test for proportions considering the weighted average of ORR of patients who had either complete or partial response per RECIST criteria in historical studies with sorafenib is 4.5%. A sample size of 25 patients was required to achieve a power of approximately 80% at a one-sided alpha level of 0.05 using a single sample Exact test for proportions. Clinical trial information: NCT03606590.