Search

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