Klaus Herfarth

Universität Heidelberg, Heidelburg, Baden-Württemberg, Germany

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Publications (185)468.47 Total impact


  • No preview · Article · Feb 2016 · Medical Physics
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    ABSTRACT: Background The standard trimodal treatment concept in locally advanced and non-metastasized non-small-cell superior sulcus tumors consists of a preoperative chemoradiation followed by surgical resection. High linear energy transfer (LET) radiation as, for example, C12 heavy-ion beam therapy theoretically offers biological advantages compared to high energy x-ray therapy as, for example, higher biological efficiency. Methods/Design In the present prospective, single-armed, open pilot study performed at the Heidelberg Ion-Beam Therapy Center (HIT) in Heidelberg, the radiation treatment within the standard trimodal concept will be exchanged against C12 heavy-ion beam treatment and apply 39GyE in 13 single fractions in combination with a chemotherapy consisting of cisplatin and vinorelbine (local standard). The primary endpoint is feasibility and safety measured by the incidence of NCI-CTCAE grade 3/4 toxicity and/or discontinuation due to any reason. Secondary endpoint is the degree of regression in the histological specimen. The main inclusion criteria are histologically confirmed non-small-cell superior sulcus tumor, nodal disease stage ≤ N2, Karnofsky performance score ≥70%, patient age between 18 and 75 years as well as written informed consent. The main exclusion criteria include medical contraindications against elements of the trimodal treatment concept, PET confirmed nodal disease stage N3, stage IV disease, prior thoracic irradiation and decompensated diseases of the lung, cardio-vascular system, metabolism, hematopoietic and coagulation system and renal function. Furthermore, patients with implanted active medical devices without certification for ion-beam therapy are not allowed to take part in the study. Trial registration number: DRKS00006323 (www.drks.de).
    Full-text · Article · Dec 2015 · BMC Cancer
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    ABSTRACT: Background and purpose Intensity-modulated particle therapy (IMPT) for tumors showing interfraction motion is a topic of current research. The purpose of this work is to compare three treatment strategies for IMPT to determine potential advantages and disadvantages of ion prostate cancer therapy. Materials and methods Simulations for three treatment strategies, conventional one-plan radiotherapy (ConvRT), image-guided radiotherapy (IGRT), and online adaptive radiotherapy (ART) were performed employing a dataset of 10 prostate cancer patients with six CT scans taken at one week intervals. The simulation results, using a geometric margin concept (7–2 mm) as well as patient-specific internal target volume definitions for IMPT were analyzed by target coverage and exposure of critical structures on single fraction dose distributions. Results All strategies led to clinically acceptable target coverage in patients exhibiting small prostate motion (mean displacement < 4 mm), but IGRT and especially ART led to significant sparing of the rectum. In 20 % of the patients, prostate motion exceeded 4 mm causing insufficient target coverage for ConvRT (V95mean = 0.86, range 0.63–0.99) and IGRT (V95mean = 0.91, range 0.68–1.00), while ART maintained acceptable target coverage. Conclusion IMPT of prostate cancer demands consideration of rectal sparing and adaptive treatment replanning for patients exhibiting large prostate motion.
    No preview · Article · Nov 2015 · Strahlentherapie und Onkologie
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    ABSTRACT: Background: Definitive, percutaneous irradiation of the prostate and the pelvic lymph nodes in high-risk prostate cancer is the alternative to prostatectomy plus lymphadenectomy. To date, the role of whole pelvis radiotherapy (WPRT) has not been clarified especially taking into consideration the benefits of high conformal IMRT (intensity modulated radiotherapy) of complex-shaped target volumes. Methods: From 2009 to 2012, 40 patients of high-risk prostate cancer with an increased risk of microscopic lymph node involvement were enrolled into this prospective phase II trial. Patients received at least two months of antihormonal treatment (AT) before radiotherapy continuing for at least 2years. Helical IMRT (tomotherapy) of the pelvic lymph nodes (51.0Gy) with a simultaneous integrated, moderate hypofractionated boost (single dose of 2.25Gy) to the prostate (76.5Gy) was performed in 34 fractions. PSA levels, prostate-related symptoms and quality of life were assessed at regular intervals for 24months. Results: Of the 40 patients enrolled, 38 finished the treatment as planned. Overall acute toxicity rates were low and no acute grade 3 or 4 gastrointestinal (GI) and genitourinary (GU) toxicity occurred. 21.6% of patients experienced acute grade 2 but no late grade ≥2 GI toxicity. Regarding GU side effects, results showed 48.6% acute grade 2 and 6.4% late grade 2 toxicity. After a median observation time of 23.4months the PLATIN 1 trial can be considered as sufficiently safe meeting the prospectively defined aims of the trial. With 34/37 patients free of a PSA recurrence it shows promising efficacy. Conclusion: Tomotherapy of the pelvic lymph nodes with a simultaneous integrated boost to the prostate can be performed safely and without excessive toxicity. The combined irradiation of both prostate and pelvic lymph nodes seems to be as well tolerated as the irradiation of the prostate alone. Trial registration: Trial Numbers: ARO 2009-05, ClinicalTrials.gov: NCT01903408.
    Preview · Article · Nov 2015 · BMC Cancer
  • A. Viardot · K. Herfarth · M. Dreyling
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    ABSTRACT: Background Indolent lymphoma is characterized by slow proliferation and long treatment-free periods. Follicular lymphoma represents the most common subgroup. Objectives This article discusses treatment strategies for follicular and other indolent lymphomas. Results In patients with advanced indolent lymphoma, treatment is indicated only if symptoms arise (watch and wait). Standard treatment is the combination of immunotherapy with the monoclonal anti-CD20 antibody rituximab with chemotherapy and in patients with follicular lymphoma this is followed by a rituximab maintenance therapy over 2 years. In localized lymphomas radiotherapy is mostly still the standard procedure. In some extranodal marginal zone lymphomas, the effective treatment of an infection (e.g. Helicobacter pylori in gastric lymphoma) can cause remission of lymphomas. Discussion Even now targeted therapies play an important role in addition to anti-CD20 antibodies and chemotherapy. The therapeutic spectrum will be expanded in the coming years.
    No preview · Article · Sep 2015 · Der Onkologe

  • No preview · Conference Paper · Jun 2015

  • No preview · Conference Paper · Jun 2015

  • No preview · Conference Paper · Jun 2015
  • S. Katayama · A. Heusel · S. Koerber · J. Debus · K. Herfarth

    No preview · Conference Paper · Jun 2015
  • A. Mohr · N. Bougatf · K. Herfarth · J. Debus

    No preview · Conference Paper · Jun 2015
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    ABSTRACT: To report our early experience with carbon ion irradiation in the treatment of gross residual or unresectable malignant peripheral nerve sheath tumors (MPNST). We retrospectively analysed 11 patients (pts) with MPNST, who have been treated with carbon ion irradiation (C12) at our institution between 2010 and 2013. All pts had measurable gross disease at the initiation of radiation treatment. Median age was 47 years (29-79). Tumors were mainly located in the pelvic/sacral (5 pts) and sinunasal/orbital region (5 pts). 5 pts presented already in recurrent situation, 3 pts had been previously irradiated, and in 3 pts MPNST were neurofibromatosis type 1 (NF1) associated. Median cumulative dose was 60 GyE. Treatment was carried out either as a combination of IMRT plus C12 boost (4 pts) or C12 only (7 pts). Median follow-up was 17 months (3-31 months). We observed 3 local progressions, translating into estimated 1- and 2-year local control rates of 65%. One patient developed distant failure, resulting in estimated 1- and 2-year PFS rates of 56%. Two patients have died, therefore the estimated 1- and 2-year OS rates are 75%. Acute radiation related toxicities were generally mild, no grade 3 side effects were observed. Severe late toxicity (grade 3) was scored in 2 patients (trismus, wound healing delays). Carbon ion irradiation yields very promising short term local control and overall survival rates with low morbidity in patients suffering from gross residual or unresectable malignant peripheral nerve sheath tumors and should be further investigated in a prospective trial.
    Full-text · Article · May 2015 · Radiation Oncology
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    ABSTRACT: To determine, in the setting of advanced-stage of Hodgkin lymphoma (HL), whether relapses occur in the irradiated planning target volume and whether the definition of local radiation therapy (RT) used by the German Hodgkin Study Group (GHSG) is adequate, because there is no harmonization of field and volume definitions among the large cooperative groups in the treatment of advanced-stage HL. All patients with residual disease of ≥2.5 cm after multiagent chemotherapy (CTX) were evaluated using additional positron emission tomography (PET), and those with a PET-positive result were irradiated with 30 Gy to the site of residual disease. We re-evaluated all sites of disease before and after CTX, as well as the PET-positive residual tumor that was treated in all relapsed patients. Documentation of radiation therapy (RT), treatment planning procedures, and portal images were carefully analyzed and compared with the centrally recommended RT prescription. The irradiated sites were compared with sites of relapse using follow-up computed tomography scans. A total of 2126 patients were enrolled, and 225 patients (11%) received RT. Radiation therapy documents of 152 irradiated patients (68%) were analyzed, with 28 irradiated patients (11%) relapsing subsequently. Eleven patients (39%) had an in-field relapse, 7 patients (25%) relapsed outside the irradiated volume, and an additional 10 patients (36%) showed mixed in- and out-field relapses. Of 123 patients, 20 (16%) with adequately performed RT relapsed, compared with 7 of 29 patients (24%) with inadequate RT. The frequency and pattern of relapses suggest that local RT to PET-positive residual disease is sufficient for patients in advanced-stage HL. Insufficient safety margins of local RT may contribute to in-field relapses. Copyright © 2015 Elsevier Inc. All rights reserved.
    No preview · Article · May 2015 · International journal of radiation oncology, biology, physics
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    ABSTRACT: A prospective study to assess toxicity and survival outcomes after intensity-modulated whole-abdominal irradiation (IM-WAI) following surgery and adjuvant intravenous carboplatin/taxane chemotherapy in advanced FIGO stage III ovarian cancer. Between 2006 and 2009, 16 patients with optimally resected FIGO stage III ovarian cancer, who had received six cycles of adjuvant carboplatin/taxane chemotherapy were treated with consolidation IM-WAI. Radiotherapy was delivered to a total dose of 30 Gy in 1.5-Gy fractions, using step-and-shoot (n = 3) or helical tomotherapy (n = 13). The first 10 patients were treated within a phase I trial; the following patients received the same treatment modality. The target volume included the entire peritoneal cavity, the diaphragm, the liver capsule, and the pelvic and para-aortic node regions. Organs at risk were kidneys, liver, heart, and bone marrow. Median follow-up was 44 months (range 19.2-67.2 months). No grade 4 toxicities occurred during IM-WAI. Common Toxicity Criteria for Adverse Events (CTCAE) grade 3 toxicities were: diarrhea (25 %), leucopenia (19 %), nausea/vomiting (6 %), and thrombocytopenia (6 %). No toxicity-related treatment break was necessary. Small bowel obstruction occurred in a total of 6 patients: in 3 cases (19 %) due to postsurgical adhesions and in 3 cases due to local tumor recurrence (19 %). Median recurrence-free survival (RFS) was 27.6 months (95 % confidence interval, CI = 24-44 months) and median overall survival (OS) was 42.1 months (95 %CI = 17-68 months). The peritoneal cavity was the most frequent site of initial failure. Consolidation IM-WAI following surgery and adjuvant chemotherapy is feasible and can be performed with manageable acute and late toxicity. The favorable RFS outcome is promising and justifies further clinical trials.
    No preview · Article · Mar 2015 · Strahlentherapie und Onkologie
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    ABSTRACT: The purpose of this work was to evaluate the results of high-dose radiation treatment using carbon ion therapy, alone or combined with intensity-modulated radiation treatment (IMRT), in patients with sacral chordoma. Between 2009 and 2012, 56 patients with sacral chordoma were treated in our center. The tumor was located above S3 in 33 patients and in S3 or below in 23 patients. In all, 41 patients received radiation therapy for the primary tumor, while 15 patients were treated for the recurrent tumor. Toxicity was measured using NCI CTCAE v.4.03. Local control (LC) and overall survival (OS) were evaluated with the Kaplan-Meier method. A total of 23 patients were irradiated with carbon ions in combination with photon IMRT, while 33 received carbon ion therapy only. Forty-three patients had a macroscopic tumor at treatment start with a median tumor size (GTV) of 244 ml (range 5-1188 ml). The median total dose was 66 Gy (range 60-74 Gy; RBE). After a median follow-up time of 25 months, the 2- and 3-year local control probability was 76 % and 53 %, respectively. The overall survival rate was 100 %. Treatment for primary tumor and male patients resulted in significant better local control. No higher toxicity occurred within the follow-up time. High-dose photon/carbon ion beam radiation therapy is safe and, especially for primary sacral chordomas, highly effective. A randomized trial is required to evaluate the role of primary definitive hypofractionated particle therapy compared with surgery with or without adjuvant radiotherapy.
    No preview · Article · Mar 2015 · Strahlentherapie und Onkologie
  • Laila König · Klaus Herfarth
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    ABSTRACT: Hintergrund und Fragestellung: Publikationen zur Low-Dose-Radiotherapie (LDRT) von indolenten Lymphomen konnten über hohe Ansprechraten berichten [1, 2, 3]. In dieser prospektiven, randomisierten, multizentrischen Phase-III-Studie aus Großbritannien wurde die Effektivität einer LDRT (2-mal 2 Gy) mit der Standardbestrahlung von 12-mal 2 Gy bei Patienten mit indolenten Lymphomen überprüft.Patienten und Methoden: Von April 2006 bis Juni 2011 wurden Patienten mit histologisch gesicherten follikulären oder Marginalzonenlymphomen der Stadien I-IV, die einen Monat zuvor keine weitere Therapie erhalten hatten, in die Studie eingeschlossen. Nach zentraler Randomisierung wurden 614 Bestrahlungsareale (299 mit 24 Gy; 315 mit 4 Gy) ausgewertet. Ziel war der Nachweis einer Nichtunterlegenheit der LDRT bezüglich lokaler Progressionsfreiheit nach zwei Jahren (primärer Endpunkt: Unterschied < 10 %; Hazard Ratio [HR] 1,37). Als sekundäre Endpunkte wurden das Gesamtüberleben, die Toxizität sowie die Leb ...
    No preview · Article · Feb 2015
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    ABSTRACT: Background: Treatment of local relapse in adenoid cystic carcinoma (ACC) following prior radiation remains a challenge: without the possibility of surgical salvage patients face the choice between palliative chemotherapy and re-irradiation. Chemotherapy yields response rates around 30% and application of tumouricidal doses is difficult due to proximity of critical structures. Carbon ion therapy (C12) is a promising method to minimize side-effects and maximize re-treatment dose in this indication. We describe our initial results for re-irradiation in heavily pre-treated ACC patients. Methods: Patients treated with carbon ion therapy between 04/2010 and 05/2013 (N=52pts, median age: 54 a) were retrospectively evaluated regarding toxicity (NCI CTC v.4), tumour response (RECIST) and control rates. 48pts (92.3%) received carbon ions only, 4pts received IMRT plus C12. Results: 4pts were treated following R1-resection, 43pts for inoperable local relapse. Most common tumour sites were paranasal sinus (36.5%), parotid (19.2%), and base of skull (17.3%). Pts received a median dose of 51GyE C12/63Gy BED and cumulative dose of 128Gy BED [67-182Gy] after a median RT-interval of 61months. Median target volume was 93ml [9-618ml]. No higher-grade (>°II) acute reactions were observed, 7pts showed blood-brain-barrier changes (°I/II: 8pts; °III: 2pts), 1 pt corneal ulceration, xerophthalmia 7pts, °IV bleeding 1 pt, tissue necrosis 2pts, otherwise no significant late reactions. Objective response rate (CR/PR) was 56.6%. With a median follow-up of 14months [1-39months] local control and distant control at 1a are 70.3% and 72.6% respectively. Of the 18pts with local relapse, 13pts have recurred in-field, 1 pt at the field edge, 3pts out of field, and one in the dose gradient. Conclusion: Despite high applied doses, C12 re-irradiation shows moderate side-effects, response rates even in these heavily pre-treated patients are encouraging and present a good alternative to palliative chemotherapy. Though most local recurrences occur within the high-dose area, further dose escalation should be viewed with caution.
    Full-text · Article · Jan 2015 · Radiotherapy and Oncology

  • No preview · Article · Dec 2014 · Radiotherapy and Oncology

  • No preview · Article · Dec 2014 · Radiotherapy and Oncology
  • Klaus Herfarth · Laila König

    No preview · Article · Dec 2014 · Strahlentherapie und Onkologie
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    ABSTRACT: The purpose of this study was to evaluate HPV-DNA and p16INK4a (p16) expression as prognostic markers for outcome in patients with anal cancer.Methods From January 2000 to December 2011 a cohort of 105 anal cancer patients was treated with definitive chemoradiation at our institution. Tumor biopsies from 90 patients were analyzed for HPV-DNA by polymerase chain reaction and for p16 expression by immunohistochemistry.ResultsMedian follow-up was 48.6 months (range 2.8–169.1 months). HPV-DNA or p16-expression was found in 75 anal cancers each (83.3%), concordance was detectable in 70 tumors (77.8%). Significantly improved overall survival (OS) [77.1% vs. 51.4%, p = 0.005], progression-free survival (PFS) [64.0% vs. 35.0%, p < 0.001] and improved local control [81.0% vs. 55.9%, p = 0.023] was found for concomitant HPV- and p16-positive anal carcinomas (cHPPAC) in univariate analysis. Multivariate analysis showed better OS [p = 0.015] and PFS [p = 0.002] for cHPPAC.Conclusion The combination of HPV-DNA and p16 can be used as an independent prognostic parameter in anal cancer patients.
    Full-text · Article · Nov 2014 · Radiotherapy and Oncology

Publication Stats

3k Citations
468.47 Total Impact Points

Institutions

  • 2000-2015
    • Universität Heidelberg
      • • Department of Radiation Oncology
      • • Abteilung Klinische Neurobiologie
      Heidelburg, Baden-Württemberg, Germany
  • 2013
    • Ludwig-Maximilians-University of Munich
      München, Bavaria, Germany
    • NCI-Frederick
      Фредерик, Maryland, United States
  • 2011-2013
    • Zentrum für Strahlentherapie und Radioonkologie
      Bremen, Bremen, Germany
    • RMIT University
      Melbourne, Victoria, Australia
    • evaplan at the University Hospital Heidelberg
      Heidelburg, Baden-Württemberg, Germany
  • 2002-2012
    • Deutsches Krebsforschungszentrum
      • • Division of Biostatistics
      • • Division of Clinical Cooperation Unit Radiation Oncology
      Heidelburg, Baden-Württemberg, Germany