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Kristin Lang, 1– 3 Rami A ElShafie, 1– 3 Sati Akbaba, 1– 3 Ronald Koschny, 4 Nina Bougatf, 1– 3, 5 Denise Bernhardt, 1– 3, 5 Stefan E Welte, 1– 3, 5 Sebastian Adeberg, 1– 3, 5 Matthias Häfner, 1– 3, 5 Steffen Kargus, 6 Peter K Plinkert, 7 Jürgen Debus, 1– 3, 5, 8 Stefan Rieken 1– 3, 5, 8 1Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg 69120, Germany; 2Heidelberg Institute of Radiation Oncology (HIRO), University Hospital of Heidelberg, Heidelberg 69120, Germany; 3National Center for Tumor Diseases (NCT), University Hospital of Heidelberg, Heidelberg, Germany; 4Department of Internal Medicine, University of Heidelberg, Heidelberg, Germany; 5Heidelberg Ion Therapy Center (HIT), University Hospital of Heidelberg, Heidelberg 69120, Germany; 6Department of Oral and Maxillofacial Surgery, University Hospital Heidelberg, Heidelberg 69120, Germany; 7Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Heidelberg, Heidelberg, Germany; 8Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg 69120, GermanyCorrespondence: Kristin LangDepartment of Radiation Oncology, University of Heidelberg, Im Neuenheimer Feld 400, Heidelberg 69120, GermanyTel +49-6221-56-8202Fax +49-6221-56-5353Email Kristin.Lang@med.uni-heidelberg.deBackground and aim: The primary aim of our study was to evaluate percutaneous endoscopic gastrostomy (PEG) tube placement depending on body weight and body mass index in patients undergoing radiotherapy (RT) for head and neck cancer (HNC). A secondary aim was to evaluate the course of weight change following PEG placement.Methods: We retrospectively reviewed the medical records of 186 patients with HNC undergoing radiotherapy (RT) or chemoradiotherapy (CRT) at our institution between January 2010 and August 2017. Initial weight and nutritional intake were analyzed prior to RT initiation and then followed throughout treatment until completion. Based on these data, the indication of PEG placement was determined. Medical records were also reviewed to analyze PEG-related acute toxicities.Results: A total of 186 patients met inclusion criteria. Patients were most commonly male (n=123, 66.1%) with squamous cell carcinoma (n=164, 88.2%). Patients who had dysphagia prior to treatment initiation as well as patients with a BMI 2 needed PEG placement earlier during the treatment course. Low-grade toxicities related to PEG insertion were observed in 10.7% patients, with peristomal pain and redness adjacent to the PEG tube insertion site being most common. High-grade toxicities, such as peritonitis and organ injury, were found in 4.9% of patients.Conclusion: Underweight patients and those with preexisting dysphagia should be closely screened during RT for weight loss and decreased oral intake. For weight loss greater than 4.5% during the treatment of HNC, early PEG-tube placement should be considered. Further prospective studies are needed to confirm these findings, and delineate a scoring system for timing of PEG use (prophylactic vs reactive) as well as assess the quality of life in patients with HNC who receive PEG placement.Keywords: head and neck cancer, radiotherapy, PEG placement, body mass index, toxicity

Sati Akbaba,1–3 Kristin Lang,1,2 Thomas Held,1,2 Klaus Herfarth,1–3 Juliane Rieber,1–3 Peter Plinkert,4 Gerd U Auffarth,5 Stefan Rieken,1–3 Juergen Debus,1–3 Sebastian Adeberg1–3 1Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg 69120, Germany; 2Heidelberg Institute of Radiation Oncology (HIRO), National Center for Radiation Research in Oncology (NCRO), University Hospital Heidelberg, Heidelberg 69120, Germany; 3Heidelberg Ion-Beam Therapy Center (HIT), University Hospital Heidelberg, Heidelberg 69120, Germany; 4Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Heidelberg, Heidelberg 69120, Germany; 5Department of Ophthalmology, University Hospital Heidelberg, Heidelberg 69120, Germany Introduction: We evaluated treatment outcomes of CIRT in an active raster-scanning technique alone or in combination with IMRT for lacrimal gland tumors.Methods: A total of 24 patients who received CIRT for a malignant lacrimal gland tumor at the HIT between 2009 and 2018 were analyzed retrospectively for LC, OS, and distant progression-free survival (DPFS) using Kaplan–Meier estimates. Toxicity was assessed according to the CTCAE version 5.Results: Median follow-up was 30 months and overall median LC, OS, and DPFS 24 months, 36 months, and 31 months, respectively. Two-year LC, OS, and DPFS of 93%, 96%, and 87% with CIRT was achieved for all patients. Local failure occurred only in patients with ACC and after a median follow-up of 30 months after the completion of RT (n=5, 21%; P=0.09). We identified a significant negative impact of a macroscopic tumor disease, which was diagnosed on planning CT or MRI before RT, on LC (P=0.026). In contrast, perineural spread (P=0.661), T stage (P=0.552), and resection margins in operated patients (P=0.069) had no significant impact on LC. No grade ≥3 acute or grade >3 chronic toxicity occurred. Late grade 3 side effects were identified in form of a wound-healing disorder 3 months after RT in one patient and temporal lobe necrosis 6 months after RT in another (n=2, 8%).Conclusion: Accelerated hypofractionated active raster-scanning CIRT for relative radioresistant malignant lacrimal gland tumors results in adequate LC rates and moderate acute and late toxicity. Nevertheless, LC for ACC histology remains challenging and risk factors for local recurrence are still unclear. Further follow-up is necessary to evaluate long-term clinical outcome. Keywords: carbon-ion radiotherapy, bimodal RT, malignant lacrimal gland tumor, adenoid cystic carcinoma, local control

Rami A El Shafie,1,2 Karina Böhm,1,2 Dorothea Weber,3 Kristin Lang,1,2 Fabian Schlaich,1,2 Sebastian Adeberg,1,2 Angela Paul,1,2,4 Matthias F Haefner,1,2 Sonja Katayama,1,2 Florian Sterzing,1,2,5 Juliane Hörner-Rieber,1,2 Sarah Löw,6 Klaus Herfarth,1,2,4 Jürgen Debus,1,2,4,7 Stefan Rieken,1,2,4 Denise Bernhardt1,2 1Department of Radiation Oncology, Heidelberg University Hospital, Heidelberg 69120, Germany; 2National Center for Radiation Oncology (NCRO), Heidelberg Institute for Radiation Oncology (HIRO), Heidelberg 69120, Germany; 3Institute of Medical Biometry and Informatics (IMBI), Heidelberg University Hospital, Heidelberg 69120, Germany; 4Heavy Ion Therapy Center (HIT), Heidelberg University Hospital, Heidelberg 69120, Germany; 5Department of Radiation Oncology, Klinikum Kempten, Kempten 87439, Germany; 6Department of Neurology, University Hospital of Heidelberg, Heidelberg 69120, Germany; 7German Cancer Research Center (DKFZ), Heidelberg 69120, Germany Background: Leptomeningeal carcinomatosis (LC) is a severe complication of metastatic tumor spread to the central nervous system. Prognosis is dismal with a median overall survival (OS) of ~10–15 weeks. Treatment options include radiotherapy (RT) to involved sites, systemic chemo- or targeted therapy, intrathecal chemotherapy and best supportive care with dexamethasone. Craniospinal irradiation (CSI) is a more aggressive radiotherapeutic approach, for which very limited data exists. Here, we report on our 10-year experience with palliative CSI of selected patients with LC. Patients and methods: Twenty-five patients received CSI for the treatment of LC at our institution between 2008 and 2018. Patients were selected individually for CSI based on clinical performance, presenting symptoms and estimated benefit. Median patient age was 53 years (IQR: 45–59), and breast cancer was the most common primary. Additional brain metastases were found in 18 patients (72.0%). RT was delivered at a TomoTherapy machine, using helical intensity-modulated radiotherapy (IMRT). The most commonly prescribed dose was 36 Gy in 20 fractions, corresponding to a median biologically equivalent dose of 40.8 Gy (IQR: 39.0– 2.5). Clinical performance and neurologic function were assessed before and in response to therapy, and deficits were retrospectively quantified on the 5-point neurologic function scale (NFS). A Cox proportional hazards model with univariate and multivariate analyses was fitted for survival.Results: Twenty-one patients died and four were alive at the time of analysis. Median OS from LC diagnosis was 19.3 weeks (IQR: 9.3–34.0, 95% CI: 11.0–32.0). In univariate analysis, a Karnofsky performance scale index (KPI) ≥70% (P=0.001), age ≤55 years at LC diagnosis (P=0.022), cerebrospinal fluid (CSF) protein

Denise Bernhardt,1–3,* Sophie Aufderstrasse,1,2,* Laila König,1–3 Sebastian Adeberg,1–4 Farastuk Bozorgmehr,5,6 Petros Christopoulos,5,6 Rami A El Shafie,1,2 Juliane Hörner-Rieber,1–3 Jutta Kappes,6,7 Michael Thomas,5,6 Felix Herth,6,7 Martin Steins,5 Jürgen Debus,1–4 Stefan Rieken1–3 1Department of Radiation Oncology, University Hospital Heidelberg, Heidelberg, Germany; 2Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany; 3Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany; 4Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; 5Department of Thoracic Oncology, Thoraxklinik, Heidelberg University, Translational Lung Research Centre Heidelberg (TLRC-H), Heidelberg, Germany; 6German Centre for Lung Research (DZL), Heidelberg, Germany; 7Department of Pneumology, Thoraxklinik, Heidelberg University, Heidelberg, Germany *These authors contributed equally to this work Background: Systemic inflammation appears to play a role in the progression of numerous solid tumors by promoting tumor proliferation. Our current study aimed to evaluate the role of inflammatory markers in limited disease (LD) small-cell lung cancer (SCLC) patients undergoing thoracic chemoradiotherapy (TCR). Patients and methods: We retrospectively analyzed a total number of 350 SCLC patients diagnosed with LD SCLC who received TCR between 1999 and 2017 and had available blood tests within 2 weeks prior to the start of TCR. Serum C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), hemoglobin (Hb) levels, and platelet count (Pc) were evaluated as potential inflammatory markers. Kaplan–Meier survival analysis was performed for overall survival (OS). For comparison of survival curves, the log-rank (­Mantel–Cox) test was used. Univariate and multivariate Cox proportional HRs were used to assess the influence of cofactors on OS. Results: Univariate analysis for OS revealed a statistically significant effect for LDH >400 U/L (HR 2.05 U/L; 95% CI 1.29–3.26 U/L; P=0.002), prophylactic cranial irradiation (PCI; HR 0.58; 95% CI 0.40–0.85; P=0.005), CRP >50 mg/L (HR 1.49 mg/L; 95% CI 1.05–2.10 mg/L; P=0.026), and Karnofsky performance scale (KPS) 70 years), Hb levels, and Pc did not influence survival. In multivariate analysis, OS was significantly affected by PCI (HR 0.64; 95% CI 0.43–0.94; P=0.026), LDH >400 U/L (HR 1.91 U/L; 95% CI 1.21–3.05 U/L; P=0.006), and CRP >50 mg/L (HR 1.43 mg/L; 95% CI 1.01–2.04 mg/L; P=0.045). KPS (≤70%) did not influence survival in multivariate analysis. Conclusion: Elevated CRP and LDH seem to be the independent prognostic factors for OS in LD SCLC patients undergoing TCR. However, elevated NLR was not found to be an independent prognostic factor for OS if taken prior to TCR. LDH and CRP are easily available blood tests and do not require additional resources for routine use and could be useful for clinical decision making. Keywords: small-cell lung cancer, limited disease, comorbidity, NLR, LDH, CRP

Mustafa Syed,1–3 Jakob Liermann,1–3 Vivek Verma,4 Denise Bernhardt,1,2 Nina Bougatf,1,3 Angela Paul,1,2 Stefan Rieken,1–3 Jürgen Debus,1–3,5 Sebastian Adeberg1,2,5 1Heidelberg Institute of Radiation Oncology, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany; 2Department of Radiation Oncology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany; 3Heidelberg Ion-Beam Therapy Center (HIT), Im Neuenheimer Feld 450, 69120 Heidelberg, Germany; 4Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE 68198, USA; 5Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany Purpose: It is hypothesized that multifocal glioblastoma (mGBM) is associated with worse prognosis compared to unifocal disease (uGBM). This study aims to investigate the differences in survival rates and progression patterns of patients between these two groups after radiation therapy. Patients and methods: We retrospectively analyzed 265 patients with primary GBM undergoing radiation therapy at the Department of Radiation Oncology, University Hospital Heidelberg, Germany, between 2004 and 2013. Of these, 202 (76%) were uGBMs and 63 (24%) were mGBMs. First, progression-free survival (PFS) and overall survival (OS) between groups were compared using the Kaplan–Meier method. Second, univariate and multivariate Cox proportional hazards regression was applied to discern prognostic and predictive factors with PFS and OS in the cohorts. Third, recurrence patterns of uGBMs and mGBMs were assessed on follow-up MRIs and compared using the chi-squared test. Results: As compared to patients with uGBM, patients with mGBM experienced significantly worse median OS (11.5 vs 14.8 months, P=0.032). Overall, 195 (73.0%) patients experienced tumor progression: 153 (75.7%) patients with uGBM and 46 (73.0%) patients with mGBM. There were no significant differences in PFS between the respective groups (6.5 vs 6.6 months, P=0.750). Of note, concomitant temozolomide treatment was associated with an OS benefit in both uGBM and mGBM by about five months (P=0.006 and P

Denise Bernhardt,1–3 Florian Sterzing,1–4,5 Sebastian Adeberg,1–4 Klaus Herfarth,1–3 Sonja Katayama,1,3 Robert Foerster,1,3,6 Juliane Hoerner-Rieber,1,3 Laila König,1,3 Juergen Debus,1–4 Stefan Rieken1,3 1Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg, Germany; 2Heidelberg Ion-Beam Therapy Center (HIT), Heidelberg, Germany; 3Heidelberg Institute of Radiation Oncology (HIRO), Heidelberg, Germany; 4Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center (DKFZ), Heidelberg, Germany; 5Department of Radiation Oncology, Klinikum Kempten, Kempten, Germany; 6Department of Radiation Oncology, University Hospital of Zürich, Zürich, Switzerland Background: Treatment of patients with pelvic adenoid cystic carcinoma (ACC) remains a challenge owing to the rarity of the disease, the lack of data, and the relative radioresistance of these tumors.Case reports: This case series presents the results of three patients with recurrent or inoperable pelvic ACC treated with intensity-modulated radiotherapy (IMRT) plus carbon ion (C12) boost. Patients received C12 therapy at a dose of 3 Gray equivalents (GyE) (relative biological effectiveness [RBE]) per fraction up to 24 GyE RBE, followed by 50 GyE of photon IMRT in 25 fractions.Conclusion: IMRT plus C12 ion boost as a definitive or adjuvant treatment for pelvic ACCs seems to be a promising therapeutic option. No unexpected toxicity was detected and the observed toxicity remained consistently low. The initial treatment response is promising and similar to that experienced for head and neck ACCs. Keywords: ACC of Bartholin’s gland, adenoid cystic carcinoma, ACC of the prostate, ion therapy, IMRT, tomotherapy, particle irradiation, carbon ion

Copyright of Der Pneumologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Tyrosine kinase inhibitors (TKI) have improved prognosis in metastatic anaplastic lymphoma kinase (ALK)‐driven lung adenocarcinoma, but patient outcomes vary widely. We retrospectively analyzed the clinical course of all cases with assessable baseline TP53 status and/or ALK fusion variant treated at our institutions (n = 102). TP53 mutations were present in 17/87 (20%) and the echinoderm microtubule‐associated protein‐like 4 (EML4)‐ALK variant 3 (V3) in 41/92 (45%) patients. The number of metastatic sites at diagnosis was affected more by the presence of V3 than by TP53 mutations, and highest with both factors (mean 5.3, p < 0.001). Under treatment with ALK TKI, progression‐free survival (PFS) was shorter with either TP53 mutations or V3, while double positive cases appeared to have an even higher risk (hazard ratio [HR] = 2.9, p = 0.015). The negative effect of V3 on PFS of TKI‐treated patients was strong already in the first line (HR = 2.5, p = 0.037) and decreased subsequently, whereas a trend for PFS impairment under first‐line TKI by TP53 mutations became stronger and statistically significant only when considering all treatment lines together. Overall survival was impaired more by TP53 mutations (HR = 4.9, p = 0.003) than by V3 (HR = 2.4, p = 0.018), while patients with TP53 mutated V3‐driven tumors carried the highest risk of death (HR = 9.1, p = 0.02). Thus, TP53 mutations and V3 are independently associated with enhanced metastatic spread, shorter TKI responses and inferior overall survival in ALK+ lung adenocarcinoma. Both markers could assist selection of cases for more aggressive management and guide development of novel therapeutic strategies. In combination, they define a patient subset with very poor outcome. What's new? This is the first study on the clinical impact of TP53 mutations in ALK‐driven lung adenocarcinoma that simultaneously considers the adverse effects of EML4‐ALK fusion variant 3. Both molecular features are independently associated with more aggressive disease course, including metastases to more organs, shorter responses to tyrosine kinase inhibitors, and worse overall survival. Their effects appear to be synergistic, and double‐positive cases have a very poor outcome. Both markers could assist patient selection for more aggressive management and help develop novel therapeutic strategies. [ABSTRACT FROM AUTHOR]

Copyright of Der Urologe A is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Strahlentherapie und Onkologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: The purpose of this work was to determine efficacy, toxicity, and patterns of recurrence after concurrent chemoradiation (CRT) in patients with extrahepatic bile duct cancer (EHBDC) and hilar cholangiocarcinoma (Klatskin tumours) in case of incomplete resection or unresectable disease.Patients and Methods: From 2003-2010, 25 patients with nonmetastasized EHBDC and hilar cholangiocarcinoma were treated with radiotherapy and CRT at our institution in an postoperative setting (10 patients, 9 patients with R1 resections) or in case of unresectable disease (15 patients). Median age was 63 years (range 38-80 years) and there were 20 men and 5 women. Median applied dose was 45 Gy in both patient groups.Results: Patients at high risk (9 times R1 resection, 1 pathologically confirmed lymphangiosis) for tumour recurrence after curative surgery had a median time to disease progression of 8.7 months and an estimated mean overall survival of 23.2 months (6 of 10 patients are still under observation). Patients undergoing combined chemoradiation in case of unresectable primary tumours are still having a poor prognosis with a progression-free survival of 7.1 months and a median overall survival of 12.0 months. The main site of progression was systemic (liver, peritoneum) in both patient groups.Conclusion: Chemoradiation with gemcitabine is safe and can be applied safely in either patients with EHBDC or Klatskin tumours at high risk for tumour recurrence after resection and patients with unresectable tumours. Escalation of systemic and local treatment should be investigated in future clinical trials. [ABSTRACT FROM AUTHOR]

Copyright of Der Onkologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background and Purpose: For palliative care of spinal bone metastases, stability assessment is of crucial importance. Pathological fractures, instability-related patient immobility and the extent of bone metastasis have been reported to affect patient outcome and these parameters have therefore been used for treatment stratification. We report on stability-dependent fracture and survival rates in over 300 non-small cell lung cancer (NSCLC) patients.Materials and Methods: Data from 303 patients with 868 osteolytic metastases treated with radiotherapy (RT) between 2000 and 2012 were evaluated retrospectively.Results: In NSCLC patients with bone metastases only, the retrospective 6- and 12-month overall survival (OS) rates were 76.7 and 47.2%, respectively. In patients with additional non-bone distant metastases, these values were 60.0 and 34.0%, respectively. Survival rates were significantly lower in patients with multiple bone metastases and in those suffering pathological fractures (p=0.017). No significant impact of histological type, location of spinal lesions or treatment regime was detected. Furthermore, stability assessment revealed no influence of vertebral column stability on patient outcome (p=0.739).Conclusion: Our analysis demonstrated a correlation between the pathological fractures of bone lesions, the number of bone metastases, additional distant metastases and survival. The results offer a rationale for future prospective investigations. [ABSTRACT FROM AUTHOR]

Radiotherapyof the resection cavity following brain metastasis (BM) resection improves local control. Single-session stereotactic radiosurgery (SRS) can reduce toxicity compared to whole-brain radiotherapy (WBRT). Hypofractionated stereotactic radiotherapy (HFSRT) can deliver a higher biologically effective dose, potentially improving local control over SRS. The ESTRON trial compared HFSRT of the cavity with post-operative WBRT in patients with 1-10 BM. Eligible patients with 1-10 newly diagnosed BM and following the resection of one BM regardless of histology were randomized 1:1 to receive HFSRT of the cavity and SRS of all unresected lesions or WBRT. A dose of 7 × 5 Gy was delivered to the cavity with a safety margin of 3-4 mm based on highly sensitive and standardized magnetic resonance imaging (MRI). The primary endpoint was intracranial control. Key secondary endpoints were overall survival (OS), safety, quality of life and neurocognitive function. 54 patients were randomized; HFSRT n=27, WBRT n=27. Most common histologies were non-small cell lung cancer (54%) and breast cancer (13%). Median cavity diameter was 28 mm (Q1-Q3: 22-33). 27 patients (52%) had at least one and 14 patients (26%) had >3 unresected BM. 15 patients (29%) had residual tumor at the cavity. These characteristics did not differ significantly between arms. At 12 months, intracranial control (IC) was 44% in the HFSRT and 59% in the WBRT arm. Median intracranial progression-free survival was 4.7 months (Q1-Q3: 1.7-18.0) in the HFSRT arm and 15.2 months (Q1-Q3: 5.6-12.7) in the WBRT arm (HR 1.72, 95%-CI: 0.94; 3.17, p = 0.080). In multivariable Cox-Regression, incomplete resection was predictive of inferior IC (HR 2.18, 95%-CI: 0.99; 4.79, p = 0.052). 3-year Local control (LC) at the cavity was 96% in the HFSRT arm and 89% in the WBRT arm (p=0.116) with a median follow-up of 19.7 months. Progression occurred distant from the cavity in 96% of cases (n = 26 out of 27). Leptomeningeal disease (LD) occurred in 7 patients (26%) in the HFSRT arm and 2 patients (7%) in the WBRT arm. LD occurred out of field in 6/7 cases in the HFSRT arm. 4 patients (15%) in the HFSRT arm and none in the WBRT arm developed blood brain barrier disruption at the cavity; 2 of those were symptomatic requiring treatment. Median OS was 10.3 months (Q1-Q3: 3.7-19.5) in the HFSRT arm and 18.6 months (Q1-Q3: 7.2-26.6) in the WBRT arm (HR 1.38, 95%-CI: 0.72; 2.66, p = 0.336). Following the resection of BM, HFSRT of the resection cavity provides excellent local control. Compared to WBRT, distant intracranial progression and LD remain a relevant risk and rigorous follow-up is warranted. Detailed analyses on neurocognitive function are pending. [ABSTRACT FROM AUTHOR]

Stereotactic Radiosurgery (SRS) is increasingly used as an alternative to whole-brain radiotherapy (WBRT) in the treatment of patients with multiple brain metastases (BM) with the aim of reducing toxicity and improving tumor control. The CYBER-SPACE trial evaluated SRS based on highly sensitive magnetic resonance imaging (MRI) for patients with 1-10 BM with the aim of avoiding or delaying WBRT. Eligible patients with 1-10 newly diagnosed BM regardless of histology were randomized 1:1 to receive SRS of all visible lesions based on either SPACE (sampling perfection with application optimized contrasts using different flip angle evolution) or MPRAGE (magnetization-prepared rapid gradient-echo) MRI sequence. If during follow-up new BM occurred, SRS was repeated for those BM. The primary endpoint was ineligibility for further SRS. It was defined as the simultaneous new occurrence or progression of more than 10 BM or leptomeningeal disease. Key secondary endpoints were overall survival (OS), safety, quality of life and neurocognitive function. 202 patients were randomized; SPACE n = 99, MPRAGE n = 103. Most common histologies were non-small cell lung cancer (63%), melanoma (16%) and breast cancer (10%). At data cutoff after 24 months, the probability of ineligibility for further SRS (iffS), considering death as a competing event was 21.7% (95%-CI: 16.1%; 27.9%) in the overall cohort, 23.9% (95%-CI: 15.9%; 32.9%) in the MPRAGE arm and 19.4% (95%-CI: 11.8%; 28.3%) in the SPACE arm. Median time to iffS was not reached in either arm. There was no significant difference between SPACE and MPRAGE in time to iffS (p=0.411). In multivariable Cox-Regression, 5-10 BM (vs. 2-4 BM) on initial MRI were predictive for shorter time to iffS (HR 3.13, 95%-CI: 1.53; 6.40, p = 0.002). Median OS was 13.1 months (Q1-Q3: 5.2-44) in both groups combined, 10.5 months (Q1-Q3: 5.1-30.4) in the SPACE arm and 15.2 months (Q1-Q3: 5.6-45.0) in the MPRAGE arm, with no significant difference between arms (p=0.585). In multivariable Cox-Regression, predictors for longer OS were a Karnofsky Performance Status >80% (HR 0.51, 95%-CI: 0.33; 0.77, p = 0.002), concomitant immunotherapy (HR 0.34, 95%-CI: 0.23; 0.52, p < 0.001) or targeted therapy (HR 0.51, 95%-CI: 0.34; 0.78, p = 0.002), however not the initial number of BM. Cause of death was known for 108 of 138 patients (78.3%). 14 patients (10.1%) died from BM, 94 patients (68.1%) from extracranial causes. SRS for patients with 1-10 BM avoided the need for WBRT in 79.2% of cases, when repeated upon occurrence of new lesions. Regular high-sensitivity MRI is a prerequisite for this strategy. Proactive management of multiple BM with SRS can greatly limit the impact of BM on overall prognosis. [ABSTRACT FROM AUTHOR]

Poster: Clinical track: Skin cancer / malignant melanoma PO-1228: Stereotactic radiosurgery with concurrent immunotherapy in malignant melanoma brain metastases J. Liermann, M. Syed, U. Neuberger, D. Reuss, R. El Shafie, W. Julia, J. Debus, J. Hassel, S. Rieken. [Extracted from the article]

Poster: Clinical track: Head and Neck PO-0816: Organs at Risk in Re-Irradiation of Head and Neck Cancer: An Individual Risk-Benefit Tradeoff T. Held, S.B. Harrabi, K. Lang, S. Akbaba, P. Windisch, D. Bernhardt, S. Rieken, K. Herfarth, J. Debus, S. Adeberg. [Extracted from the article]