Deviating HER2 test results in gastric cancer: analysis from the prospective multicenter VARIANZ study.

PURPOSE: The prospective multicenter VARIANZ study aimed to identify resistance biomarkers for HER2-targeted treatment in advanced gastric and esophago-gastric junction cancer (GC, EGJC). HER2 test deviations were found in 90 (22.3%) of 404 cases (central versus local testing) and were associated with negative impact on survival for trastuzumab-treated patients. Here, we investigated methodological and biological variables that may promote deviating HER2 test results. METHODS: We analyzed HER2 testing procedures and participation in quality assurance programs of 105 participating local pathology laboratories. Furthermore, tumor localization and histological subtypes were compared between patients with centrally confirmed (central HER2 + /local HER2 + , n = 68) and unconfirmed HER2 status (central HER2 -/local HER2 + , n = 68). RESULTS: For central HER2 testing, concordance between in situ hybridization (ISH) and immunohistochemistry (IHC) was 98.3%, with IHC sensitivity of 93.3% (84 IHC + of 90 ISH +), specificity of 99.5% (389 IHC- of 391 ISH-), and a positive diagnosis rate of 97.7%. Central confirmation of the local HER2 IHC scores were seen for the majority of locally HER2- IHC 0/1 (172/178; 96.6%), but less frequently for locally IHC3 + (57/124; 46.0%) cases. Deviation rate was not associated with IHC antibody platform used in the local pathology institute neither with participation in quality-assuring tests. Regarding tumor characteristics, deviating test results were more frequently found in GC vs. EGJC (69.1% vs. 39.7%; p = 0.001) and in Laurén diffuse vs. intestinal subtype (23.5% vs. 5.9%, p = 0.004). CONCLUSION: Tumor localization and histological subtype have an impact on HER2 test deviation rates. Assessment of HER2 remains challenging for GC and EGJC.

Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) - Part 2 with Recommendations on Psycho-oncology, Rehabilitation, Follow-up, Recurrence, Palliative Therapy and Healthcare Facilities.

Aim This is an update of the interdisciplinary S3-guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL), published in March 2021. The work on the updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics ( Deutsche Gesellschaft für Gynäkologie und Geburtshilfe , DGGG) and the Working Group on Gynecological Oncology ( Arbeitsgemeinschaft Gynäkologische Onkologie , AGO) of the German Cancer Society ( Deutsche Krebsgesellschaft , DKG). Method The process used to update the 2014 S3-guideline was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or - if evidence was lacking - on the consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which would take account of more recently published literature and the recent appraisal of new evidence. Recommendations The short version of this guideline consists of recommendations and statements on palliative therapy and follow-up of patients with cervical cancer. The most important aspects included in this updated guideline are the new FIGO classification published in 2018, the radical open surgery approach used to treat cervical cancer up to FIGO stage IB1, and the use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis.

Diagnosis, Therapy and Follow-up of Cervical Cancer. Guideline of the DGGG, DKG and DKH (S3-Level, AWMF Registry No. 032/033OL, May 2021) - Part 1 with Recommendations on Epidemiology, Screening, Diagnostics and Therapy.

Aim This update of the interdisciplinary S3 guideline on the Diagnosis, Therapy and Follow-up of Cervical Cancer (AWMF Registry No. 032/033OL) was published in March 2021. This updated guideline was funded by German Cancer Aid (Deutsche Krebshilfe) as part of the German Guideline Program in Oncology. The guideline was coordinated by the German Society of Gynecology and Obstetrics ( Deutsche Gesellschaft für Gynäkologie und Geburtshilfe , DGGG) and the Working Group on Gynecological Oncology ( Arbeitsgemeinschaft Gynäkologische Onkologie , AGO) of the German Cancer Society ( Deutsche Krebsgesellschaft , DKG). Method The process of updating the S3 guideline dating from 2014 was based on an appraisal of the available evidence using the criteria of evidence-based medicine, adaptations of existing evidence-based national and international guidelines or - if evidence was lacking - on a consensus of the specialists involved in compiling the update. After an initial review of the current literature was carried out according to a prescribed algorithm, several areas were identified which, in contrast to the predecessor version from September 2014, required new recommendations or statements which took account of more recently published literature and the appraisal of the new evidence. Recommendations The short version of this guideline consists of recommendations and statements on the epidemiology, screening, diagnostic workup and therapy of patients with cervical cancer. The most important new aspects included in this updated guideline include the newly published FIGO classification of 2018, the radical open surgery approach for cervical cancers up to FIGO stage IB1, and use of the sentinel lymph node technique for tumors ≤ 2 cm. Other changes include the use of PET-CT, new options in radiotherapy (e.g., intensity-modulated radiotherapy, image-guided adaptive brachytherapy), and drug therapies to treat recurrence or metastasis.

The WNT5A/ROR2 signaling pathway in pancreatic ductal adenocarcinoma (PDAC).

PURPOSE: WNT5A/ROR2 signaling pathway has been involved in many human cancers. Its role in pancreatic ductal adenocarcinoma (PDAC) has not been clarified yet. The purpose of this study was to determine the prognostic value of WNT5A expression in conjunction with the ROR2 expression in the same PDAC human tissues. METHODS: We retrospectively analyzed by immunohistochemistry the WNT5A and ROR2 expression in117 paraffin-embedded PDAC specimens following surgical pancreatic resection. The prognostic value of WNT5A and ROR2 was assessed using Kaplan-Meier survival curves and multivariate Cox regression models. RESULTS: High ROR2 expression was detected in 65.8% (77/117) of PDAC tumors, in 28.2% (33/117) in tumor-stroma, and in 71.1% (65/90) of normal pancreatic tissue. High WNT5A expression was found in 76.9% (90/117) of tumors, in 59.0% (69/117) of tumor-stroma, and in 83.0% (73/88) of normal pancreatic tissue. Spearman's correlation coefficiency demonstrated weak association between ROR2 and WNT5A expression in tumor (r=0.184; p=0.047), and no association in stroma (r=0.036; p=0.699). Multivariate analysis showed that regional lymph node invasion and differentiation were independent prognostic factors of survival, while ROR2- and WNT5A expression were not. CONCLUSIONS: Variable expression patterns for ROR2 and WNT5A were demonstrated in PDAC and normal pancreatic tissues suggesting a role for WNT5A/ROR2 signalling pathway, not only in PDAC but also in the normal pancreatic tissue during inflammation. The lack of prognostic significance for ROR2 and WNT5A expression in our cohort, either alone or in subgroup analysis, underlines the complexity of their role in PDAC, which is highly dependent on the different molecular receptor-ligand tissue contexts.

Late toxicities and recurrences in patients with clinical stage I non-seminomatous germ cell tumours after 1 cycle of adjuvant bleomycin, etoposide and cisplatin versus primary retroperitoneal lymph node dissection - A 13-year follow-up analysis of a phase III trial cohort.

BACKGROUND: One cycle of adjuvant chemotherapy with bleomycin, etoposide and cisplatin (BEP) has shown superiority in recurrence-free survival over retroperitoneal lymph node dissection (RPLND) in patients with clinical stage (CS) I non-seminomatous germ cell tumours (NSGCTs) of the testis in the setting of a phase III trial. We report the recurrences and late toxicities of this study after 13 years of follow-up. METHODS: Questionnaires from 382 patients with CS I NSGCT treated with 1 cycle of adjuvant BEP (arm A) or RPLND + two cycles of adjuvant BEP in cases of pathological stage II disease (arm B) were evaluated regarding recurrences and late toxicity. Overall, information on recurrence status was available in 337 patients, and 170 questionnaires were evaluable for toxicity (arm A: 95; arm B: 75). RESULTS: With a median follow-up of 13.8 years (0-22), 3 patients (1.6%) in arm A and 16 patients (8.4%) in arm B experienced recurrence. The 15-year PFS in arm A/B was 99% (CI 96-100%)/92% (CI 89-99%) (p = 0.0049). The 15-year OS in arm A/B was 93% (CI 87-97%)/93% (CI 86-97%) (p = 0.83). Eight patients (4.2%) in arm A and four patients (2.1%) in arm B showed metachronous secondary testicular cancer (p = 0.26). Five patients (2.6%) in arm A and four patients (2.1%) in arm B developed other malignancies. Toxicities were not significantly different apart from retrograde ejaculation, which occurred more frequently after RPLND (10% versus 24%, p = 0.01). CONCLUSIONS: With long-term observation, one cycle of BEP remains superior to RPLND in preventing recurrence and was tolerated without any clinically relevant long-term toxicities.

HER2 Expression, Test Deviations, and Their Impact on Survival in Metastatic Gastric Cancer: Results From the Prospective Multicenter VARIANZ Study.

PURPOSE: Trastuzumab is the only approved targeted drug for first-line treatment of human epidermal growth factor receptor 2-positive (HER2+) metastatic gastric cancer (mGC). However, not all patients respond and most eventually progress. The multicenter VARIANZ study aimed to investigate the background of response and resistance to trastuzumab in mGC. METHODS: Patients receiving medical treatment for mGC were prospectively recruited in 35 German sites and followed for up to 48 months. HER2 status was assessed centrally by immunohistochemistry and chromogenic in situ hybridization. In addition, HER2 gene expression was assessed using qPCR. RESULTS: Five hundred forty-eight patients were enrolled, and 77 had HER2+ mGC by central assessment (14.1%). A high deviation rate of 22.7% between central and local test results was seen. Patients who received trastuzumab for centrally confirmed HER2+ mGC (central HER2+/local HER2+) lived significantly longer as compared with patients who received trastuzumab for local HER2+ but central HER2- mGC (20.5 months, n = 60 v 10.9 months, n = 65; hazard ratio, 0.42; 95% CI, 8.2 to 14.4; P < .001). In the centrally confirmed cohort, significantly more tumor cells stained HER2+ than in the unconfirmed cohort, and the HER2 amplification ratio was significantly higher. A minimum of 40% HER2+ tumor cells and a HER2 amplification ratio of ≥ 3.0 were calculated as optimized thresholds for predicting benefit from trastuzumab. CONCLUSION: Significant discrepancies in HER2 assessment of mGC were found in tumor specimens with intermediate HER2 expression. Borderline HER2 positivity and heterogeneity of HER2 expression should be considered as resistance factors for HER2-targeting treatment of mGC. HER2 thresholds should be reconsidered. Detailed reports with quantification of HER2 expression and amplification levels may improve selection of patients for HER2-directed treatment.

Management of Germ Cell Tumours of the Testes in Adult Patients: German Clinical Practice Guideline, PART II - Recommendations for the Treatment of Advanced, Recurrent, and Refractory Disease and Extragonadal and Sex Cord/Stromal Tumours and for the Management of Follow-Up, Toxicity, Quality of Life, Palliative Care, and Supportive Therapy.

OBJECTIVES: We developed the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up of germ cell tumours (GCT) of the testes in adult patients. We present the guideline content in 2 separate publications. The present second part summarizes therecommendations for the treatment of advanced disease stages and for the management of follow-up and late effects. MATERIALS AND METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search in March 2018), were provided. Thirty-one experts, who were entitled to vote, rated the final clinical recommendations and statements. RESULTS: Here we present the treatment recommendations separately for patients with metastatic seminoma and non-seminomatous GCT (stages IIA/B and IIC/III), for restaging and treatment of residual masses, and for relapsed and refractory disease stages. The recommendations also cover extragonadal and sex cord/stromal tumours, the management of follow-up and toxicity, quality-of-life aspects, palliative care, and supportive therapy. CONCLUSION: Physicians and other medical service providers who are involved in the diagnostics, treatment, and follow-up of GCT (all stages, outpatient and inpatient care as well as rehabilitation) are the users of the present guideline. The guideline also comprises quality indicators for measuring the implementation of the guideline recommendations in routine clinical care; these data will be presented in a future publication.

Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.

INTRODUCTION: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages. METHODS: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements. RESULTS: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma. CONCLUSION: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes.

No enhanced (p-) α-synuclein deposition in gastrointestinal tissue of Parkinson's disease patients.

BACKGROUND: Neuronal alpha-synuclein (α-Syn) aggregation in the brain is believed to be a central component of the pathogenesis of Parkinson's disease (PD). α-Syn aggregates in the gastrointestinal tract have been suggested as a potential biomarker of PD that may even signal an early event of the Parkinsonian molecular pathology. However, studies further investigating this hypothesis have produced mixed results. OBJECTIVE: To determine whether the prevalence of α-Syn- and serine 129-phosphorylated α-Syn (Ser129p-α-Syn) depositions detected in intestine from PD patients differed from that of non-Parkinsonian controls. METHODS: In this retrospective study, we examined post-mortem small and large intestine samples of 25 PD patients and 20 age- and sex-matched controls without PD. Specimens were taken from archived paraffin-embedded tissue blocks. Immunohistochemical techniques were applied to detect α-Syn and Ser129p-α-Syn aggregates in situ. Immunoreactivity was quantified by a new approach that employed the detailed assessment of α-Syn- and Ser129p-α-Syn-positive morphological structures of the enteric nervous system (i.e., nerve fibers, myenteric and submucous plexus as well as ganglion cells). RESULTS: α-Syn immunoreactivity was a common finding in intestinal tissues from PD patients and controls. Importantly, α-Syn and Ser129p-α-Syn immunoreactivity were significantly reduced in PD patients compared to controls in each of the morphological structures examined. CONCLUSIONS: Immunohistochemical detection of intestinal α-Syn and Ser129p-α-Syn seems to be a frequent and potentially normal finding. Neither α-Syn nor Ser129p-α-Syn immunoreactivity may, therefore, be regarded as a molecular intestinal biomarker of PD pathology. Reduced intestinal α-Syn and Ser129p-α-Syn immunoreactivity in PD patients rather reflect PD-related neuronal degeneration.

Biopsy rate and nonalcoholic steatohepatitis (NASH) in patients with nonalcoholic fatty liver disease (NAFLD).

Background: Licensed therapies for nonalcoholic fatty liver disease (NAFLD) do not yet exist, but clinical trials are testing treatment options. Inclusion criteria often require liver biopsy showing fibrosis (F2/3) or cirrhosis (F4) and nonalcoholic steatohepatitis (NASH). However, histological criteria pose a serious obstacle for recruitment.Aims: Characterize the relevance of liver biopsies in the selection of patients with NAFLD.Methods: Patients between 2013 and 2018 with the ICD-10 code K76.0 were analyzed. Fibrosis was defined by the NASH clinical research network (CRN) fibrosis staging system, NASH by a NAFLD activity score (NAS) ≥4. Predictive factors were determined by logistic regression.Results: Liver biopsy was performed in 87/638 (13.6%) patients (49% female, age 52.5 ± 14.0, BMI 30.4 ± 5.9 kg/m2). Fibrosis stage F0/F1/F2/F3/F4 was observed in N = 7/47/7/17/9, an NAS ≥4 in N = 27. Fibrosis stage F2/F3 and F4 along with NAS ≥4 was found in 1.7% and 0.5% of cases. Liver stiffness measurement, LSM (OR 2.3 per doubling of value; CI 1.3-4.4, p = .005) and FIB-4 (OR 2.3 per doubling of value; CI 1.2-4.4, p = .012) were significant predictors for fibrosis ≥ F2. Predictive factors for NASH were not identified.Conclusion: The biopsy rate in NAFLD patients is low and fibrosis ≥ F2 along with NAS ≥4 only present in a few cases. Transient elastography and FIB-4 are useful to select patients at risk for fibrosis for liver biopsy.

A Human REPIN1 Gene Variant: Genetic Risk Factor for the Development of Nonalcoholic Fatty Liver Disease.

OBJECTIVES: We tested the hypothesis that a genetic deletion (Del) variant in the REPIN1 gene is associated with the severity of nonalcoholic fatty liver disease (NAFLD) in humans. METHODS: Sixty-three donors of liver biopsies from individuals with obesity and different degrees of NAFLD and fibrosis were screened for a Del REPIN1 gene variant and liver REPIN1 mRNA expression. RESULTS: In 8 homozygous Del carriers, we found significantly lower NAFLD activity and fibrosis scores compared with 55 wild-type allele carriers. DISCUSSION: A Del variant of REPIN1 may be associated with a lower risk of the development of NAFLD.

Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) in patients with peritoneal metastasized colorectal, appendiceal and small bowel cancer.

BACKGROUND: Patients with intestinal cancer (colorectal, appendiceal, and small bowel) with peritoneal metastases (PM) have a poor prognosis. We assessed whether pressurized intraperitoneal aerosol chemotherapy (PIPAC) together with systemic chemotherapy is an effective treatment option for these entities in palliative intent. METHODS: Between November 2015 and February 2018, prospective data registry was performed (NCT03100708). Thirteen patients with intestinal cancer (median age 61 years [range 49-77]) underwent 26 PIPAC procedures with a median number of 2 interventions per patient (range 1-6). A chemoaerosol consisting of cisplatin/doxorubicin was administered during standard laparoscopy. RESULTS: The median peritoneal carcinomatosis index according to Sugarbaker before the first PIPAC was 14 (range 2-27), and the median ascites volume was 10 mL (range 0-6300 mL). Six patients who received 2 or more PIPAC procedures had decreased and stable ascites volumes, while only 1 patient displayed increased ascites. The median overall survival was 303 days (range 30-490) after the first PIPAC procedure. CONCLUSIONS: PIPAC offers a novel treatment option for patients with PM. Our data show that PIPAC is safe and well-tolerated. Ascites production can be controlled by PIPAC in patients with intestinal cancer. Further studies are required to document the significance of PIPAC within palliative therapy concepts. TRIAL REGISTRATION: NCT03100708.

Tumor-associated macrophages and individual chemo-susceptibility are influenced by iron chelation in human slice cultures of gastric cancer.

Purpose: Presence of tumor-associated macrophages (TAM) and high levels of ferritin and lipocalin 2 (Lcn2) in the tumor microenvironment are associated with poor prognosis in many types of cancer. Here we investigate whether iron deprivation influences TAM phenotype and chemotherapy resistance in tumor slice cultures (TSC) of gastric cancer. Results: TAM remained morphologically and functionally stable for four DIV. DFO treatment for 72 h decreased ferritin expression in TAM and in the tumor stroma but did not alter Lcn2 expression. TAM phenotype was altered after 72 h of cisplatin or DFO treatment compared with control conditions. Single DFO treatment and combined treatment with cytotoxic drugs significantly increased tumor cell apoptosis in TSC of gastric cancer. Methods: TSC were manufactured by cutting tissue of gastric cancer resection specimens in 350 µm thick slices and cultivating them under standard conditions on a filter membrane, at an air-liquid interface. After 24 h ex vivo, TSC were treated with irinotecan (100 nM) or cisplatin (10 µM) alone and in combination with deferoxamine (DFO; 10 µM, 100 µM), respectively, for 72 h. After four days in vitro (DIV) the TSC were fixated with paraformaldehyde, paraffin embedded and analyzed by immunohistochemistry for apoptosis (cPARP), proliferation (Ki67), TAM (CD68, CD163), ferritin, and Lcn2 expression. Conclusions: TAM are well preserved and can be studied in TSC of gastric cancer. Iron deprivation significantly increased tumor cell apoptosis.

Retroperitoneal space-occupying lesion with displacement of the inferior vena cava.

INTRODUCTION: The differential diagnosis and therapy of retroperitoneal masses suspicious for soft tissue tumors remains difficult and needs individual decisions as to the best management of patients. We report an unusual case of retroperitoneal schwannoma (RS). PRESENTATION OF CASE: We report on a 57-year-old female patient with a retroperitoneal space-occupying lesion with displacement, but no infiltration of surrounding vessels, especially the inferior vena cava. As presence of malignancy could not be completely excluded by imaging and biopsy, we performed an open resection of the tumor with plastic reconstruction of the right renal vein. Curative resection of the tumor could be achieved and benign RS verified. DISCUSSION: Preoperative work-up, including a broad spectrum of differential diagnoses, and consecutive appropriate surgical resection are challenging. Characteristic features of the pre-therapeutic diagnostics of retroperitoneal schwannomas are discussed and differential diagnostic considerations as well as surgical therapeutic options are outlined. CONCLUSION: Deeper understanding of retroperitoneal schwannomas gained from preoperative radiologic diagnostics may serve to underline the need for targeted biopsy. This and its histopathological examination necessitate expert interventional radiologists and pathologists. Thus, even the pre-therapeutic diagnostic management should be performed in a specialized center. If doubts remain regarding the entity of the retroperitoneal lesion and findings are still controversial after thorough assessment, surgical oncologic resection represents the therapy of choice, if the surgical risk is adequate.

Cancer of the anal region.

Anal canal accounts for 2% of all cancer and its incidence increases with age with a predominance in woman. About 80% of all primary anal canal cancers are squamous; adenocarcinoma arising from the glands or glandular ducts shows a behaviour that is similar to that of the adenocarcinoma of the rectum. Risk factors includes sexually transmitted infection with Human Papillomavirus, cigarette smoking, immunosuppression, and sexual practices. The standard treatment for anal canal is chemo - radiation with a combination of fluoropyrimidines and mitomycin or cisplatin. Salvage surgery may be necessary for residual disease after radiotherapy or chemoradiation, for locoregional relapse and/or for sequelae. In the metastatic setting a multidisciplinary approach is preferred and includes medical treatment, surgery, and RT, if appropriate. Discussing these possible options in the initial stage is of most importance to ensure the best quality of life (QoL) for patients.

Correction to: Predictive risk factors for lymph node metastasis in patients with resected non-small cell lung cancer: a case control study.

The original article [1] contains slight errors whereby several terms in the first column of Tables 1, 2, and 3 have an erroneous 'p' preceding them.

Predictive risk factors for lymph node metastasis in patients with resected non-small cell lung cancer: a case control study.

BACKGROUND: Estimation of lymph node status is essential in order to determine precise therapy for patients with non-small cell lung cancer (NSCLC). Furthermore, lymph node involvement is a very powerful prognostic factor in these patients. In this analysis, we aim to evaluate the predictive factors for lymph node metastasis in NSCLC-patients. METHODS: In a prospectively-established database, we analyzed all data of patients with NSCLC, who underwent oncological surgical resections from 01/2007 to 12/2016, retrospectively. The correlation between clinicopathological parameters and lymph node metastasis was investigated by using univariate and binary logistic regression analysis. RESULTS: In this study, we operated on 204 consecutive patients, 142 men (71.7%) and 56 women (28.3%). Lymph node metastases were detected in 38.2% (78/204). Preoperatively, central tumor localization (OR = 2.6, 95% CI = 1.3-5.1, P = 0.005) and tumor size > 3 cm (OR = 2.5, 95% CI = 1.3-4.4, P = 0.005) were found to be significant predictive factors for lymph node metastasis. Postoperatively, multivariate analysis showed that intratumoral lymph vessel invasion (L1-status) (OR = 17.3, 95% CI = 5.1-58.4, P <  0.001) along with the central tumor localization (OR = 2.8, 95% CI = 1.4-5.8, P = 0.004) were significantly associated with lymph node metastasis. In small size tumors (≤3 cm), two predictive factors for lymph node metastasis were found: central tumor localization (OR = 19.4, 95% = 2.1-186.4, P = 0.01) and L1-status (OR = 43.9, 95% CI = 3.6-529.4, P = 0.003). CONCLUSIONS: A precise pre- and intraoperative assessment of the lymph node status is essential in patients with larger sized tumors and central localization. Furthermore, L1-status is a highly significant risk factor for lymph node metastasis in NSCLC-Patients. Therefore, an adjuvant therapy in patients with L1-status and pNX category should be considered.