Hans Hoffmann

Universität Heidelberg, Heidelburg, Baden-Württemberg, Germany

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Publications (173)527.67 Total impact

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    ABSTRACT: There is controversy whether patients diagnosed with large-cell neuroendocrine carcinoma (LCNEC) should be treated according to protocols for non-small cell lung cancers (NSCLC) or small cell lung cancers (SCLC), especially with regard to the administration of prophylactic cranial irradiation (PCI). This study was set up to determine the incidence of brain metastases and to investigate the outcome following multimodal treatment in 70 patients with LCNEC. Seventy patients with histologically confirmed LCNEC were treated at the University Hospital of Heidelberg between 2001 and 2014. Data were collected retrospectively. Al most all patients received thoracic surgery as initial treatment (94 %). Chemotherapy was administered in 32 patients as part of the initial treatment. Fourteen patients were treated with adjuvant or definitive thoracic radiotherapy according to NSCLC protocols. Cranial radiotherapy due to brain metastases, mostly given as whole brain radiotherapy (WBRT), was received by fourteen patients. Statistical analysis was performed using the long-rank test and the Kaplan–Meier method. Without PCI, the detected rate for brain metastases was 25 % after a median follow-up time of 23.4 months, which is comparable to NSCLC patients in general. Overall (OS), local (LPFS), brain metastases-free survival (BMFS) and extracranial distant progression-free survival (eDPFS) was 43, 50, 63 and 50 % at 5 years, respectively. Patients with incomplete resection showed a survival benefit from adjuvant radiotherapy. The administration of adjuvant chemotherapy improved the general worse prognosis in higher pathologic stages. In LCNEC patients, the administration of radiotherapy according to NSCLC guidelines appears reasonable and contributes to acceptable results of multimodal treatment regimes. The low incidence of spontaneous brain metastases questions a possible role of PCI.
    European journal of medical research 08/2015; 20(1). DOI:10.1186/s40001-015-0158-9 · 1.40 Impact Factor
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    ABSTRACT: We have sequenced the genomes of 110 small cell lung cancers (SCLC), one of the deadliest human cancers. In nearly all the tumours analysed we found bi-allelic inactivation of TP53 and RB1, sometimes by complex genomic rearrangements. Two tumours with wild-type RB1 had evidence of chromothripsis leading to overexpression of cyclin D1 (encoded by the CCND1 gene), revealing an alternative mechanism of Rb1 deregulation. Thus, loss of the tumour suppressors TP53 and RB1 is obligatory in SCLC. We discovered somatic genomic rearrangements of TP73 that create an oncogenic version of this gene, TP73Δex2/3. In rare cases, SCLC tumours exhibited kinase gene mutations, providing a possible therapeutic opportunity for individual patients. Finally, we observed inactivating mutations in NOTCH family genes in 25% of human SCLC. Accordingly, activation of Notch signalling in a pre-clinical SCLC mouse model strikingly reduced the number of tumours and extended the survival of the mutant mice. Furthermore, neuroendocrine gene expression was abrogated by Notch activity in SCLC cells. This first comprehensive study of somatic genome alterations in SCLC uncovers several key biological processes and identifies candidate therapeutic targets in this highly lethal form of cancer.
    Nature 07/2015; DOI:10.1038/nature14664 · 42.35 Impact Factor
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    ABSTRACT: Due to the high etiological diversity and the potential for malignancy, pulmonary nodules represent a clinical challenge, becoming increasingly frequent as the number of CT examinations rises. The topic gains even more importance as clear evidence for the effectiveness of CT screening was provided by the National Lung Screening Trial (NLST). Yet, the results were tempered by the high false-positive rate and the requirement of performing further diagnostic procedures. The management of those detected solitary pulmonary nodules is currently based on the individuals' risk of developing lung cancer, the pulmonary nodule characteristics and the capability of diagnostic and therapeutic approaches. © 2015 S. Karger AG, Basel.
    Respiration 06/2015; DOI:10.1159/000430996 · 2.92 Impact Factor
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    ABSTRACT: The best therapy for patients with stage I non-small cell lung cancer (NSCLC) who are medically unfit for lobectomy or prefer not to undergo surgery has not yet been demonstrated. We analyzed data from our prospective database to evaluate the recurrence and survival rates and assess the extent to which the type of treatment explains outcome differences. This study included 116 patients with histologically proven clinical stage I NSCLC who were treated with sublobar resection (SLR; n = 42), radiofrequency ablation (RFA; n = 25) or radiotherapy (RT; n = 49) between 2009 and 2013. The primary end point was the time to primary tumor recurrence (PR). Kaplan-Meier curves and Cox regression were used to compare the recurrence patterns and survivals after adjustments for potential confounders. The SLR patients were younger and exhibited better performance status. The RT patients had larger tumors. After adjusting for age and tumor size, there were differences between the different treatments in terms of the PR rate, but no differences were observed in overall (OS) or disease-free survival. The hazard ratio for PR comparing SLR versus RT adjusted for age and tumor size was 2.73 (95% confidence interval, CI, 0.72-10.27) and that for SLR versus RFA was 7.57 (95% CI 1.94-29.47). Our study suggests that SLR was associated with a higher primary tumor control rate compared to RFA or RT, although the OSs were not different. These results should be confirmed in prospective trials. © 2015 S. Karger AG, Basel.
    Respiration 04/2015; DOI:10.1159/000381555 · 2.92 Impact Factor
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    ABSTRACT: To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early stage disease and locally-advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally-advanced disease. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Annals of Oncology 04/2015; DOI:10.1093/annonc/mdv187 · 6.58 Impact Factor
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    ABSTRACT: Pneumonectomy is associated with significant postoperative mortality. This study was undertaken to develop and validate a risk model of mortality following pneumonectomy. We reviewed our prospective database and identified 774 pneumonectomies from a total of 7792 consecutive anatomical lung resections in the years 2003 to 2010 (rate of pneumonectomy: 9.9%). Based on data from 542 pneumonectomies between 2003 and 2007 (i.e., the "discovery set"), a penalized multivariable logistic regression analysis was performed to identify preoperative risk factors. A risk model was developed and validated in an independent data set of 232 pneumonectomies that were performed between 2008 and 2010 (i.e., the "validation set"). Of the 542 patients in the discovery set (DS), 35 patients (6.5%) died after pneumonectomy during the same admission. We developed a risk prediction model for in-hospital mortality following pneumonectomy; that model included age, current alcohol use, coronary artery disease, preoperative leukocyte count and palliative indication as possible risk factors. The risk model was subsequently successfully validated in an independent data set (n = 232) in which 18 patients (7.8%) died following pneumonectomy. For the validation set, the sensitivity of the model was 53.3% (DS: 54.3%), the specificity was 88.0% (DS: 87.4%), the positive predictive value was 26.7% (DS: 22.9%) and the negative predictive value was 95.8% (DS: 96.5%). The Brier score was 0.062 (DS: 0.054). The prediction model is statistically valid and clinically relevant.
    PLoS ONE 04/2015; 10(4):e0121295. DOI:10.1371/journal.pone.0121295 · 3.23 Impact Factor
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    ABSTRACT: The promise of benefits from lung cancer screening is tempered by the false positive rate and the need to perform diagnostic procedures to determine the aetiology of the solitary pulmonary nodules (SPN) identified. We have developed a novel procedure which allows sampling of SPNs via a transparenchymal approach, and report the results from this as a first in human trial. This study was a prospective single-arm interventional study. We recruited patients with a SPN detected on CT imaging, which was suspicious for lung cancer, who were suitable for surgical resection. Using the subject's CT, an optimal airway wall point of entry (POE), and an avascular path through lung tissue from the POE to the SPN was calculated. A tunnel tract was created from the POE to the nodule using a set of catheter-based tools under fused fluoroscopy guidance. The patients proceeded to surgical resection immediately after the biopsy. The participants were followed-up for 6 months after the procedure. The primary endpoint of the study was to evaluate the feasibility to access and biopsy the nodule. Twelve patients were recruited, and a tunnel pathway created in 10 patients. There were no adverse events during the procedures. Adequate biopsies were obtained from 10 patients (83%), which correlated with the histological findings from the surgical resection. Inspection of the resected lobes did not raise any safety concerns and indicated appropriately tunnelled pathways to the nodule. This first in human study demonstrates that bronchoscopic transparenchymal access of SPNs is feasible. NCT02130115. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
    Thorax 03/2015; 70(4). DOI:10.1136/thoraxjnl-2014-206211 · 8.56 Impact Factor
  • Michael Klopp · Hans Hoffmann · Hendrik Dienemann
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    ABSTRACT: A chest tube is used to drain the contents of the pleural space to reconstitute the physiologic pressures within the pleural space and to allow the lungs to fully expand. Indications for chest tube placement include pneumothorax, hemothorax, pleural effusion, pleural empyema, and major thoracic surgery. The most appropriate site for chest tube placement is the 4th or 5th intercostal space in the mid- or anterior- axillary line. Attention to technique in placing the chest tube is vital to avoid complications from the procedure. Applying the step-by-step technique presented, placement of a chest tube is a quick and safe procedure. Complications - frequently occurring when the tube is inserted with a steel trocar - include hemothorax, dislocation, lung lacerations, and injury to organs in the thoracic or abdominal cavity." © Georg Thieme Verlag KG Stuttgart · New York.
    DMW - Deutsche Medizinische Wochenschrift 03/2015; 140(5):339-42. DOI:10.1055/s-0041-100725 · 0.55 Impact Factor
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    ABSTRACT: Introduction: In recent years, percutaneous radiofrequency ablation (RFA) has been developed as a new tool in the treatment of non-small cell lung cancer (NSCLC) in non-surgical patients. There is growing evidence that RFA-mediated necrosis can modulate host immune responses. Here we analyzed serum inflammatory factors as well as immunosuppressive cells in the peripheral blood to discover possible prognostic indicators.Patients and Methods: Peripheral blood and serum samples were collected before RFA and within 3 months after the treatment in a total of 12 patients. Inflammatory cytokines and growth factors were measured in serum by the Bio-Plex assay. Myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) were evaluated in the peripheral blood via flow cytometry.Results: In patients developing local or lymphogenic tumor relapse (n=4), we found an early significant increase in the concentration of tumor necrosis factor (TNF)-α as well as chemokine (C-C motif) ligand (CCL)-2 and CCL-4 as compared to patients without relapse (n=4) and healthy donors (n=5). These changes were associated with an elevated activity of circulating MDSC indicated by an increased nitric oxide (NO) production in these cells.Discussion: Elevated serum levels of TNF-α, CCL-2 and CCL-4 associated with an increased NO production in circulating MDSCs might be an early indicator of the incomplete RFA and subsequently a potential tumor relapse in NSCLC. This article is protected by copyright. All rights reserved.
    Clinical & Experimental Immunology 01/2015; 180(3). DOI:10.1111/cei.12596 · 3.28 Impact Factor
  • Hans Hoffmann
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    ABSTRACT: Bronchial sleeve resections are defined as removal of a segment of a main bronchus, typically in conjunction with the involved lobar or segmental bronchus and associated lung tissue with subsequent construction of a bronchial anastomosis. In patients with lung cancer, they allow for preservation of lung tissue unaffected by tumor while achieving an oncological radical resection. In many instances, a sleeve lobectomy can avoid an otherwise required pneumonectomy or offer a curative resection to otherwise functionally inoperable patients.
    Chest Surgery, 01/2015: pages 185-208; , ISBN: 978-3-642-12043-5
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    ABSTRACT: Idiopathic interstitial pneumonias (IIP) are associated with an increased lung cancer (LC) risk. However, data on the prognostic and therapeutic impact are limited. We therefore aimed to analyze the outcome of IIP patients with LC under different treatment modalities. Patients with IIPs diagnosed in a tertiary interstitial lung diseases (ILD) center were reviewed for LC diagnosis. Of 265 patients with idiopathic pulmonary fibrosis (IPF), 142 with non-specific interstitial pneumonia (NSIP), and 71 with cryptogenic organizing pneumonia (COP), 16%, 4%, and 6% were affected byLC, respectively. Patient characteristics were: IPF: 93% male, median age 67 years, forced vital capacity (FVC) 82%, diffusion capacity for Carbon monoxide (DLCO) 41%, mean survival 20 months. NSIP: 67% male, median age 70 years, FVC 72%, DLCO 43%, mean survival 35 months. COP: 50% male, median age 66 years, FVC 93%, DLCO 77%, mean survival 88 months. Significant treatment-related toxicities occurred in 55% IPF, 20% NSIP und 0% COP patients. 30-days postoperative mortality was 25% in IPF, and 0% in NSIP/COP while rate of radiation pneumonitis was 24% in IPF. LC is a frequent comorbidity in IIP, with a higher incidence and reduced survival in IPF compared to other IIPs. LC treatment is associated with significant toxicity, specifically in IPF. Interdisciplinary evaluation of therapeutic options in IIP patients diagnosed with LC is therefore mandatory.
    Sarcoidosis, vasculitis, and diffuse lung diseases: official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders 01/2015; 31(4):266-274. · 1.74 Impact Factor
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    ABSTRACT: Purpose The purpose of this study was to evaluate postoperative radiotherapy regarding outcome and toxicity in patients with thymic epithelial tumors (TET) after surgery. Materials and methods We retrospectively analyzed medical records of 41 patients with TET treated with postoperative radiotherapy at our institution between 1995 and 2012. The impact of prognostic factors (e.g., Masaoka stage, histological subtype) was investigated and radiation-related toxicity was assessed. Results Median age was 59.8 years and median follow-up was 61 months. In 24.4 %, TETs were associated with paraneoplastic syndromes. The 5-year overall survival (OS) was 89.5 % and the 5-year disease-free survival (DFS) was 88.9 %. Masaoka stage had a significant impact on OS (p = 0.007). Locally limited stages I + II had a 5-year OS of 100 % compared to 80 % for stage III and 66.7 % for stage IV. The 5-year DFS was excellent with 100 % for both WHO groups A/AB/B1 and B2, respectively, and significantly (p = 0.005) differed from B3/C-staged patients with a 5-year DFS of 63.6 %. Resection status, paraneoplastic association, radiation dose, or tumor size did not influence survival. There were no high-grade acute or late side effects caused by radiotherapy. Conclusion Masaoka stage has a significant impact on OS as WHO type has on DFS in patients with TETs after surgery and adjuvant irradiation. Postoperative radiotherapy with doses around 50 Gy is safe and not likely to cause high-grade toxicity. Further prospective trials are necessary to separate patient subgroups that benefit from radiotherapy from those that do not.
    Strahlentherapie und Onkologie 08/2014; 191(2). DOI:10.1007/s00066-014-0740-z · 2.73 Impact Factor
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    ABSTRACT: Background Treatment of locally advanced non-small-cell lung cancer is based on a combined approach. To study the impact of trimodal therapy for stage III-N2 NSCLC a single centre retrospective evaluation focusing on survival and therapy-related toxicity was performed. Methods 71 patients diagnosed between March 2001 and August 2008 with pathologically confirmed stage III-N2 non-small-cell lung cancer at the University Clinic of Heidelberg were retrospectively analyzed. All patients were treated within trimodal therapy strategies including surgery, induction or adjuvant chemotherapy and postoperative radiotherapy. Overall survival (OS) and disease free survival (DFS) rates were calculated using the Kaplan-Meier method. The log-rank test and Fishers Exact test were applied for univariate analysis and Cox proportional regression model for multivariate analysis. Results Median survival was 32 months. 1-, 3- and 5-year overall survival (OS) rates were 84.5%, 49.6% and 35.5% respectively. Disease free survival rates at 1, 3 and 5 years were 70.4%, 41.8% and 27.4% respectively. 9 patients (12.6%) were diagnosed with a local recurrence. Multivariate analysis did not reveal any independent prognostic factors for OS, but indicated a trend for pT stage and type of surgery. In regard to toxicity 8.4% of the patients developed a clinically relevant ≥ grade 2 pneumonitis. Evaluation of the forced expiratory volume in 1 second per unit of vital capacity (FEV1/VC) before and 1-3 years post radiotherapy revealed a median decrease of 2.1%. Conclusions Our descriptive data indicate that trimodal therapy represents an effective and safe treatment approach for patients with stage III-N2 non-small-cell lung cancer. Further prospective clinical trials are necessary in order to clearly define the impact of multimodal strategies and optimize NSCLC treatment.
    BMC Cancer 08/2014; 14(1):572. DOI:10.1186/1471-2407-14-572 · 3.32 Impact Factor
  • Oncology Research and Treatment 08/2014; 37 Suppl 3(s3):58-66. DOI:10.1159/000365234
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    ABSTRACT: Background:Uncontrolled proliferation is a hallmark of malignant tumour growth. Its prognostic role in non-small cell lung cancer (NSCLC) has been investigated in numerous studies with controversial results. We aimed to resolve these controversies by assessing the Ki-67 proliferation index (PI) in three large, independent NSCLC cohorts.Methods:Proliferation index was retrospectively analysed by immunohistochemistry in a cohort of 1065 NSCLC and correlated with clinicopathological data including outcome and therapy. Results were validated in two independent cohorts of 233 squamous cell carcinomas (SQCC) and 184 adenocarcinomas (ADC).Results:Proliferation index (overall mean: 40.7%) differed significantly according to histologic subtypes with SQCC showing a mean PI (52.8%) twice as high as ADC (25.8%). In ADC PI was tightly linked to growth patterns. In SQCC and ADC opposing effects of PI on overall (OS), disease-specific and disease-free survival were evident, in ADC high PI (optimised validated cut-off: 25%) was a stage-independent negative prognosticator (hazard ratio, HR OS: 1.56, P=0.004). This prognostic effect was largely attenuated by adjuvant radio-/chemotherapy. In SQCC high PI (optimised validated cut-off: 50%) was associated with better survival (HR OS: 0.65, P=0.007).Conclusions:Our data demonstrate that PI is a clinically meaningful biomarker in NSCLC with entity-dependent cut-off values that allow reliable estimation of prognosis and may potentially stratify ADC patients for the need of adjuvant therapy.British Journal of Cancer advance online publication, 22 July 2014; doi:10.1038/bjc.2014.402 www.bjcancer.com.
    British Journal of Cancer 07/2014; 111(6). DOI:10.1038/bjc.2014.402 · 4.82 Impact Factor
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    ABSTRACT: Malignant pleural mesothelioma (MPM) is associated with asbestos exposure and is a cancer that has not been significantly impacted by small molecule-based targeted therapeutics. Previously, we demonstrated the existence of functional subsets of lung cancer and head and neck squamous cell carcinoma (HNSCC) cell lines in which fibroblast growth factor receptor (FGFR) autocrine signaling functions as a non-mutated growth pathway. In a panel of pleural mesothelioma cell lines, FGFR1 and FGF2 were co-expressed in 3 of 7 cell lines and were significantly associated with sensitivity to the FGFR-active tyrosine kinase inhibitor (TKI), ponatinib, both in vitro and in vivo using orthotopically propagated xenografts. Furthermore, RNAi-mediated silencing confirmed the requirement for FGFR1 in specific mesothelioma cells and sensitivity to the FGF ligand trap, FP-1039, validated the requirement for autocrine FGFs. None of the FGFR1-dependent mesothelioma cells exhibited increased FGFR1 gene copy number, based on a FISH assay, indicating that increased FGFR1 transcript and protein expression were not mediated by gene amplification. Elevated FGFR1 mRNA was detected in a subset of primary MPM clinical specimens and like MPM cells, none harbored increased FGFR1 gene copy number. These results indicate that autocrine signaling through FGFR1 represents a targetable therapeutic pathway in MPM and that biomarkers distinct from increased FGFR1 gene copy number such as FGFR1 mRNA would be required to identify MPM patients bearing tumors driven by FGFR1 activity. Implications: FGFR1 is a viable therapeutic target in a subset of malignant pleural mesotheliomas, but FGFR TKI-responsive tumors will need to be selected by a biomarker distinct from increased FGFR1 gene copy number, possibly FGFR1 mRNA or protein levels.
    Molecular Cancer Research 06/2014; 12(10). DOI:10.1158/1541-7786.MCR-14-0038 · 4.50 Impact Factor
  • Interactive Cardiovascular and Thoracic Surgery 06/2014; 18(suppl 1):S17-S17. DOI:10.1093/icvts/ivu167.66 · 1.11 Impact Factor
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    ABSTRACT: Background In the era of improving overall survival rates of malignant diseases, the impact of a previous malignancy (PM) on treatment and outcome of lung cancer (LC) remains unclear. Methods We reviewed all LC patients from our institution that were treated from 2004 to 2006 for the occurrence of LC with PM excluding patients with multiple primary LC. Results A total of 444 and 2698 LC patients with and without a history of a PM were identified (prevalence of 14.1%). PM were most often located in breast (15.5%), prostate (14.9%), bladder (9.0%) and kidney (8.8%). Compared to never smokers, patients with nicotine consumption had more often a cancer history of prostate, gastrointestinal, and the head-neck region. The median interval until diagnosis of LC was 72.2 months (range 0-537 months) with most LC diagnosed 5 years after PM diagnosis. With a similar distribution of histology, stage and localization compared to controls, NSCLC patients with PM and stage IV disease showed a favourable overall survival (p<0.0001). In contrast, SCLC patients had similar survival curves (n.s.). Conclusions A considerable subgroup of LC patients has a history of PM that may indicate a favorable prognostic factor. However, these patients should be treated similar to other LC patients.
    Respiratory medicine 06/2014; 108(6). DOI:10.1016/j.rmed.2014.02.015 · 2.92 Impact Factor

Publication Stats

2k Citations
527.67 Total Impact Points


  • 2004–2015
    • Universität Heidelberg
      • Department of Thoracic Surgery
      Heidelburg, Baden-Württemberg, Germany
  • 2014
    • Deutsche Gesellschaft für Thoraxchirurgie
  • 2012
    • Charité Universitätsmedizin Berlin
      • Institute of Pathology
      Berlín, Berlin, Germany
  • 1997
    • National Cerebral and Cardiovascular Center
      • Department of Cardiovascular Medicine
      Ōsaka, Ōsaka, Japan
  • 1993–1997
    • Ludwig-Maximilian-University of Munich
      • • Cardiac Surgery Clinic
      • • Department of Surgery
      München, Bavaria, Germany