Large Cell Neuroendocrine Cancer Research Articles

Surgery with adjuvant chemotherapy versus chemoradiation for early-stage large cell neuroendocrine cancer (LCNEC) of the lung: A SEER plus based analysis.

e20616 Background: LCNEC of the lung is a rare and highly aggressive tumor with neuroendocrine differentiation. Given its rare occurrence and lack of data from large randomized trials, treatment recommendations are based on the extrapolation of data, primarily from small-cell lung cancer studies. We conducted this study to evaluate the survival difference among patients with LCNEC with an N1 disease between those who received surgery and adjuvant chemotherapy versus definitive chemotherapy and radiotherapy. Methods: We utilized Surveillance, Epidemiology, and End Results (SEER) plus 18 registries database to identify patients diagnosed with LCNEC with tumor stage of T1, T2, or T3 and nodal stage of N1. The study population included patients, 18 years and above, who underwent surgical resection followed by adjuvant chemotherapy and patients who received definitive chemo-radiotherapy for early stage LCNEC. Kaplan-Meier and log rank test were used to compare overall survival (OS) and Cancer specific survival (CSS). Multivariate survival analysis was done using the cox proportional hazards regression model. Results: A total of 178 patients were included, 57.3% (n = 102) were < 65-year-old, 50.56% (n = 90) were male, mostly Caucasian 87.08% (n = 155) and identified as non-Hispanic 93.26% (n = 166). Out of them, 70.22% (n = 125) underwent surgery plus adjuvant chemotherapy and 29.78% (n = 53) underwent chemoradiation. Patients who underwent surgery with adjuvant chemotherapy had higher overall survival (OS) than chemoradiation (37 vs. 11 months respectively). 3-year (49.9% vs. 15.7%) and 5-year OS rates (36.7% vs. 10.4%) were also higher in the earlier group. On multivariate analysis after adjusting for age, gender, race and origin, patients who received chemoradiation had higher hazards as compared to those who received surgery and adjuvant chemotherapy (Hazard ratio: 2.91, 95% Confidence interval (CI):1.93,4.37, P value < 0.001). When examining the cancer specific survival (CSS), similar results were observed with higher CSS in the surgery with adjuvant chemotherapy group (18 vs. 8 months) reaching a statistical significance of P < 0.001 and higher hazards in chemoradiation group (Hazard ratio: 3.33, 95% Confidence interval (CI):2.09,5.28, P value < 0.001). 3-year survival (26.47% vs. 2.7 %) and 5-year CSS rates (11.76% vs. not reached) were also pronounced in the patients treated with surgery with adjuvant chemotherapy. Conclusions: Our study demonstrates that patients with early stage LCNEC (T1-3 N1) disease treated with surgery and adjuvant chemotherapy had statistically significant overall and cancer specific survival rates compared to those treated with chemoradiation.

Efficacy and safety of PD-1/PD-L1 inhibitor plus platinum-based chemotherapy vs. platinum-based chemotherapy alone in patients with previously untreated advanced large-cell neuroendocrine cancer of the lung.

9066 Background: Large-cell neuroendocrine carcinoma (LCNEC) is a rare tumor with a poor prognosis and limited treatment options. The efficacy of first-line therapies for LCNEC has not yet been established. This study evaluated the efficacy and safety of the combination of PD-1/PD-L1 inhibitor and platinum-based chemotherapy in treatment-naïve patients with advanced LCNEC. Methods: We retrospectively analyzed patients with advanced LCNEC who were treated with a PD-1/PD-L1 inhibitor plus platinum-based chemotherapy (PD-1/PD-L1 inhibitor group) or with platinum-based chemotherapy alone (chemotherapy group) based on data obtained from electronic databases of three participating cancer centers from January 2015 to August 2022. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were evaluated for each group. Safety was assessed in all patients who received at least one dose of their assigned treatment. Results: Among the 75 enrolled patients, 25 were allocated to receive PD-1/PD-L1 inhibitor plus platinum-based chemotherapy and 50 were allocated to receive platinum-based chemotherapy alone (patients were matched 1:2 on baseline characteristics). The median PFS was 15.1 months (95% confidence interval [CI], 7.1–23.2) in the PD-1/PD-L1 inhibitor group and 5.3 months (95% CI, 4.4–6.2) in the chemotherapy group (hazard ratio [HR], 0.26; 95% CI, 0.113–0.428; p < 0.0001). The 12-month OS was 88.0% (95% CI, 67.7–96.9) in the PD-1/PD-L1 inhibitor group and 56.0% (95% CI, 41.4–69.7) in the chemotherapy group ( p = 0.0056). The ORRs in the two groups were 40% and 16%, respectively ( p = 0.022), and the DCRs were 96% and 70%, respectively ( p = 0.010). Regarding safety, the most common incidences of grade ≥ 3 adverse events involved neutropenia, leukopenia, anemia, and fatigue. There were no significant differences between the two groups. Immune-related adverse events (irAEs) in the PD-1/PD-L1 inhibitor group included cutaneous hemangiomas, hypothyroidism, anaphylaxis, and pneumonitis. Grade 3 or 4 irAEs were not observed. No new safety signals were noted. Conclusions: First-line PD-1/PD-L1 inhibitor plus platinum-based chemotherapy significantly improved PFS in patients with advanced LCNEC compared with platinum-based chemotherapy alone.

EP14.01-013 First-Line Chemotherapy vs Chemoimmunotherapy in Stage IV Large Cell Neuroendocrine Carcinoma of the Lung, a Retrospective Study

Large cell neuroendocrine cancer of lung (LCNEC) is a rare type of lung cancer and data regarding the effect of immune checkpoint inhibitors (ICI) on LCNEC is limited. This retrospective study aims to investigate the efficacy of adding ICI to standard chemotherapy (CT) in the treatment of patients with stage IV LCNEC.

Based on the Development and Verification of a Risk Stratification Nomogram: Predicting the Risk of Lung Cancer-Specific Mortality in Stage IIIA-N2 Unresectable Large Cell Lung Neuroendocrine Cancer Compared With Lung Squamous Cell Cancer and Lung Adenocarcinoma.

BackgroundThe purpose of this study is to predict overall survival (OS) and lung cancer-specific survival (LCSS) in patients with stage IIIA-N2 unresectable lung squamous cell cancer (LUSC), lung adenocarcinoma (LUAD), and large cell neuroendocrine cancer (LCNEC) by constructing nomograms and to compare risk and prognostic factors affecting survival outcomes in different histological subtypes.MethodsWe included 11,505 unresectable NSCLC patients at stage IIIA-N2 between 2010 and 2015 from the Surveillance, Epidemiology, and End Results (SEER) database. Moreover, competition models and nomograms were developed to predict prognostic factors for OS and LCSS.ResultsAnalysis of the SEER database identified 11,505 NSCLC patients, of whom 5,559 (48.3%) have LUAD, 5,842 (50.8%) have LUSC, and 104 (0.9%) have LCNEC. Overall, both OS and LCSS were significantly better in stage IIIA-N2 unresectable LUAD than in LCNEC, while there was no statistically significant difference between LUSC and LCNEC. Age, gender, T stage, chemotherapy, and radiotherapy were significantly associated with OS rates in LUAD and LUSC. However, chemotherapy was the only independent factor for LCNEC (p < 0.01).From competitive risk models, we found that older age, larger tumors, non-chemotherapy and non-radiotherapy were associated with a increased risk of death from LUAD and LUSC. Unlike prognostic factors for OS, our study showed that both chemotherapy and radiotherapy were all LCNEC-specific survival factors for both LCSS and non-LCSS LCNEC.ConclusionOur study reports that unresectable patients with stage IIIA-N2 LCNEC and LUSC have worse LCSS than LUAD. The study’s first prognostic nomogram constructed for patients with unresectable stage IIIA-N2 NSCLC can accurately predict the survival of different histological types, which may provide a practical tool to help clinicians assess prognosis and stratify these prognostic risks to determine which patients should be given an optimized individual treatment strategy based on histology.

Adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers as prognostic factors of early-stage large-cell neuroendocrine carcinoma.

BackgroundWe investigated whether adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers affected survival of patients with the early stage of large‐cell neuroendocrine cancer.MethodsThis was a retrospective multicenter study including consecutive patients undergoing resection of node negative large‐cell neuroendocrine carcinoma. Five‐year survival and disease‐free survival rate were evaluated by the Kaplan–Meier method and the log‐rank test in relation to adjuvant chemotherapy, extent of resection, and immunoistochemical neuroendocrine markers (synaptophysin, chromogranin A, and neuron‐specific enolase).ResultsOur study population included 117 patients; 47 (40%) of these received adjuvant chemotherapy. Patients treated with adjuvant chemotherapy had better survival (74% vs. 45%, p = 0.002) and disease‐free survival (79% vs. 40%, p = 0.001) in all cases except patients with tumor <20 mm (79.5% vs. 57.4%, p = 0.43). Lobectomy compared to sublobar resection was associated with better survival (67% vs. 0.1%, p < 0.0001) and disease‐free survival (65% vs. 0.1%, p < 0.0001) also in patients with tumor <20 mm (79% vs. 28%, p = 0.001). Patients with triple‐positive neuroendocrine markers had better survival (79% vs. 35%, p = 0.0001) and disease‐free survival (69% vs. 42%, p = 0.0008). Regression analysis showed that tumor size <20 mm, lobectomy, adjuvant chemotherapy, and triple‐positive immunistochemical neuroendocrine markers were significant favorable prognostic factors for survival outcomes.ConclusionsLobectomy seems to be the management of choice in patients with large‐cell neuroendocrine cancer <20 mm while adjuvant chemotherapy should be administered only in patients with tumor >20 mm.

The Role of Conventionally Fractionated Radiotherapy and Stereotactic Radiotherapy in the Treatment of Carcinoid Tumors and Large-Cell Neuroendocrine Cancer of the Lung.

Simple SummaryPatients with neuroendocrine neoplasms (NETs) are a rare group of patients, 70% of which are diagnosed in the location of tumors in the digestive system, and the remaining 30% in the respiratory system. Building an appropriate therapeutic strategy in a patient with NET requires the involvement of a multidisciplinary team, which should include: oncology surgeon, clinical oncologist and radiation oncologist. One of the commonly used methods of treating lung NETs is the use of radiotherapy. However, the number of available recommendations for treatment of NET radiotherapy is negligible. This poses a significant problem for radiation oncologists when making qualification decisions for treatment with radiant energy. The aim of this article was to present the current knowledge on the use of radiotherapy in the treatment of lung NETs. In addition, we hope that the description of clinical cases in this publication will help radiation oncologists make the best, often personalized qualification decisions.The occurrence of neuroendocrine tumors among the diagnosed neoplasms is extremely rare and is associated with difficulties in undertaking effective therapy due to the histopathological differentiation of individual subtypes and the scarce clinical data and recommendations found in the literature. The choice of treatment largely depends not only on its type, but also on the location and production of excess hormones by the tumor itself. Common therapeutic approaches include surgical removal of the tumor, the use of chemotherapy, targeted drug therapy, peptide receptor radionuclide therapy, and the use of radiation therapy. This article reviews the current knowledge on the classification and application of radiotherapy in the treatment of lung NETs. Case reports were presented in which treatment with conventional radiotherapy, radical and palliative radiochemotherapy, as well as stereotactic fractionated radiotherapy in the treatment of typical (TC) and atypical (AT) lung carcinoids and large cell neuroendocrine carcinoma (LCNC) were used. We hope that the solutions presented in the literature will allow many radiation oncologists to make the best, often personalized decisions about the therapeutic qualifications of patients.

PTPN3 is a potential target for a new cancer immunotherapy that has a dual effect of T cell activation and direct cancer inhibition in lung neuroendocrine tumor

In our previous study, we found that inhibition of protein tyrosine phosphatase non-receptor type 3 (PTPN3), which is expressed in lymphocytes, enhances lymphocyte activation, suggesting PTPN3 may act as an immune checkpoint molecule. However, PTPN3 is also expressed in various cancers, and the biological significance of PTPN3 in cancer cells is still not well understood, especially for lung neuroendocrine tumor (NET).Therefore, we analyzed the biological significance of PTPN3 in small cell lung cancer and examined the potential for PTPN3 inhibitory treatment as a cancer treatment approach in lung NET including small cell lung cancer (SCLC) and large cell neuroendocrine cancer (LCNEC).Experiments in a mouse xenograft model using allo lymphocytes showed that PTPN3 inhibition in SCLC cells enhanced the anti-tumor effect of PTPN3-suppressed activated lymphocytes. In addition, PTPN3 was associated with increased vascularization, decreased CD8/FOXP3 ratio and cellular immunosuppression in SCLC clinical specimens. Experiments in a mouse xenograft model using autocrine lymphocytes also showed that PTPN3 inhibition in LCNEC cells augmented the anti-tumor effect of PTPN3-suppressed activated lymphocytes. In vitro experiments showed that PTPN3 is involved in the induction of malignant traits such as proliferation, invasion and migration. Signaling from PTPN3 is mediated by MAPK and PI3K signals via tyrosine kinase phosphorylation through CACNA1G calcium channel. Our results show that PTPN3 suppression is associated with lymphocyte activation and cancer suppression in lung NET. These results suggest that PTPN3 suppression could be a new method of cancer treatment and a major step in the development of new cancer immunotherapies.

Patterns of lung cancer in people living with human immunodeficiency virus (HIV): A retrospective, single-center study in Washington, D.C.

e21154 Background: Lung cancer is the leading cause of cancer death and the most common non-acquired immune deficiency syndrome defining malignancy in people living with HIV (PLWH). Disparities in outcomes have been observed despite lung cancer mortality reportedly decreasing in the general population over the last decade due to lower rates of smoking and the advent of novel therapies. To better understand the current trend in lung cancer in PLWH, we explored demographic characteristics, comorbidities, and lung cancer pathology and molecular data in this population. Methods: A retrospective search of patient charts was conducted from 2004 to January 2021 using billing codes for HIV and primary lung cancer. Patients who had incorrect HIV or primary lung cancer diagnoses were excluded. Results: The search yielded 45 patients, of which 11 were excluded as described above: 66% were males, 82% African American, and 18% Caucasian. About two-thirds of patients were living in zip codes with predominantly low to medium household incomes. The median pack years of patients diagnosed with Stage I or II non-small cell lung cancer (NSCLC) was 40, Stage III or IV NSCLC was 20, early stage small cell lung cancer (SCLC) was 30, and late stage SCLC was 60. The median time between HIV and lung cancer diagnoses was 21.7 years for Stage I or II NSCLC, 17.1 years for Stage III or IV NSCLC, 15.2 for early stage SCLC, and 13.3 for late stage SCLC. Of 26 patients with viral load (VL) data, 21 (80.7%) had VL less than 500 when lung cancer was diagnosed. Of the 33 charts with available pathology data, there were 16 adenocarcinomas, 6 squamous carcinomas, 3 adenosquamous carcinomas, 1 large cell neuroendocrine cancer, 4 SCLCs, 1 mesothelioma, and 2 unspecified NSCLCs. Of 19 patients with a histologic grade, 11 had a high-grade tumor (57.9%). For the NSCLCs, 8 were Stage I (28.5%), 2 Stage II (7.1%), 8 Stage III (28.5%), 9 Stage IV (32.1%), and 1 with an unspecified stage. One SCLC was early stage and the remaining 3 were late stage. Five patients had brain metastasis. Molecular data or PDL-1 expression was available for 10 adenocarcinomas (62.5%), 1 adenosquamous (33%), 3 squamous carcinomas (50%), and the large cell neuroendocrine cancer. An EGFR mutation was detected in 2 cancers. ALK rearrangement was found in 1. Other mutations were detected. Two cancers were in each PDL1 expression category: &lt; 1%, 1-50%, and &gt; 50%. Conclusions: Our study suggests that PLWH with lung cancer continue to have high rates of smoking. Viral load was well controlled. A range in stages of lung cancer was observed including earlier stages. Although molecular data was limited, available EGFR and ALK gene alterations, and PD-L1 expression prevalence were on par with that of the general population. With advancements in lung cancer treatment, additional research is needed in the PLWH population to better understand and mitigate disparities.

Antiaging gene Klotho regulates epithelial‑mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin‑2 expression

Epithelial-mesenchymal transition (EMT) is considered to serve an important role in the metastatic/invasive ability of cancer cells, in the acquisition of drug resistance, and in metabolic reprogramming. In the present study, it was hypothesized that the Klotho gene is involved in the metastatic/invasive ability of lung cancer. We previously reported an association between Klotho expression and overall survival in patients with small cell lung cancer and large cell neuroendocrine cancer. We also found that Klotho expression was associated with EMT-related molecules in lung squamous cell carcinoma. The present study aimed to analyze the function of the Klotho gene and to elucidate its relevance to the regulation of the EMT. For this purpose, GFP-Klotho plasmids were transfected into lung adenocarcinoma cells (A549) and cell lines with stable expression (A549/KL-1 and A549/KL-2) were established. A549/KL-1 cells expressed higher levels of Klotho protein by western blot analysis compared with A549/KL-2 cells. In western blotting of A549 and A549/KL-1 cells, the expression of the mesenchymal marker N-cadherin was found to be completely inhibited in A549/KL-1 cells suggesting that Klotho expression may regulate the EMT in cancer cells via the inhibition of N-cadherin. The results of the sensitivity tests demonstrated that A549/KL-1 cells were significantly more sensitive to pemetrexed compared with A549 cells (IC50 A549/KL-1 vs. A549 cells, 0.1 µM vs. 0.7 µM). The results of the microarray analysis demonstrated that a very high level of lipocalin-2 (LCN2) expression was induced in the A549/KL-1 cells. Klotho overexpression completely suppressed the expression of mesenchymal markers, such as N-cadherin and Snail1 (Snail). The results of the present study suggested that there may be a new mechanism of action for the antitumor effects of pemetrexed, namely, LCN2-mediated modulation of N-cadherin expression. Klotho expression during cancer treatment has great potential as a predictor for efficacy of pemetrexed and as a factor in the selection of personalized medicine for postoperative adjuvant chemotherapy.

A comparison study of dual-energy spectral CT and 18F-FDG PET/CT in primary tumors and lymph nodes of lung cancer.

We aimed to investigate whether there is a correlation between dual-energy spectral computed tomography (DESCT) and 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) parameters in primary tumor and metastatic lymph nodes in patients with newly diagnosed lung cancer. Primary tumor and metastatic lymph nodes of 68 patients diagnosed with lung cancer were evaluated retrospectively with 18F-FDG PET/CT and DESCT imaging. The histologic subtypes were adenocarcinoma (n=29), squamous cell carcinoma (SCC) (n=26), small cell lung cancer (SCLC) (n=11), and large cell neuroendocrine cancer (LCNEC) (n=2). In terms of PET parameters, SUVmax, SUVmean, SULmax, SULmean, SULpeak, and normalized SUL values were obtained for primary tumors and metastatic lymph nodes. In terms of DESCT parameters, maximum and mean iodine content (IC), normalized IC values, iodine enhancement (IE) and normalized IE values were calculated. We found no correlation between DESCT and 18F-FDG PET/CT parameters in primary tumors and metastatic lymph nodes. In addition, no correlation was found in the analysis performed in any of the histologic subgroups. In patients with a primary tumor <3 cm, there was a moderate negative correlation between the parameters SUVmax-ICmax (r= -0.456, p = 0.043), SUVmean-ICmax (r= -0.464, p = 0.039) SULmean-ICmax (r= -0.497, p = 0.026), SUVmax-ICmean (r= -0.527, p = 0.020), SULmean-ICmean (r= -0.499, p = 0.025), and SULpeak-ICmean (r= -0.488, p = 0.029). We consider that DESCT and 18F-FDG PET/CT indicate different characteristics of the tumors and should not supersede each other.

Outcomes of Patients with Pulmonary Large Cell Neuroendocrine Carcinoma in I-IV Stage.

Background and Objectives: Large cell neuroendocrine cancer is characterised by poor prognosis. The standard of treatment is still not established. The aim of this study was to assess the predictive factors of overall survival (OS) and progression-free survival (PFS) of pulmonary large cell neuroendocrine carcinoma (LCNEC) and combined LCNEC. Materials and Methods: All patients had confirmed pathology stage I-IV disease recorded between period 2002–2018. Survival curves were estimated by Kaplan–Meier method. Uni- and multivariable analysis was conducted using Cox-regression analysis. Results: A total of 132 patients with LCNEC and combined LCNEC were included. Half of them had clinical stage IIIB/C-IV. Patients were treated with radical (n = 67, including surgery alone; resection with neo-adjuvant or adjuvant chemotherapy, radiochemotherapy, or adjuvant radiotherapy; patients treated with radiochemotherapy alone), palliative (n = 41) or symptomatic (n = 24) intention. Seventeen patients were treated with resection margin R1 or R2. Non-small cell carcinoma (NSCLC) chemotherapy (platinum-vinorelbine; PN schedule) and small-cell lung carcinoma (SCLC) chemotherapy approaches (platinum/carboplatinum-etoposide; PE/KE schedule) were administered in 20 and in 55 patients, respectively. The median (95% Confidence Interval (CI)) OS and PFS were 17 months (9.0–36.2 months) and 7 months (3.0–15.0 months), respectively. Patients treated with negative resection margin, with lower clinical stage, without lymph node metastasis, and with size of primary tumour ≤4 cm showed significantly better OS and PFS. The main risk factors with an adverse effect on survival were advanced CS and positive resection margin. Conclusions: Patients with LCNEC characterized poor prognosis. Independent prognostic factors influencing PFS were initial clinical stage and resection margin R0 vs. R1-2.

Brief Report on the Efficacy of Nivolumab in Patients With Previously Treated Advanced Large-Cell Neuroendocrine Cancer of the Lung

IntroductionThe optimal management of large cell neuroendocrine cancer of the lung (LCNEC) is unclear, and data regarding anti–programmed cell death protein 1 (PD-1) antibodies are scarce. This study reports the clinical efficacy of a PD-1 inhibitor in patients with advanced LCNEC. MethodsAll patients with stage III to IV LCNEC treated with at least one previous cycle of chemotherapy between January 1, 2015 and December 31, 2018 were reviewed retrospectively. Patients were divided into two groups depending on their exposure to nivolumab as second-line treatment or beyond. The primary objective was to assess nivolumab’s efficacy. ResultsA total of 51 patients with advanced LCNEC from eight centers were analyzed, including 17 who received nivolumab. The PD-1 inhibitor was used as second-line treatment in 77% of cases, with a median number of eight doses (range: 1–62). After nivolumab treatment, the median overall survival was 12.1 months (95% confidence interval [CI]: 7.10–14.20). The objective response rate was 29.4% (95% CI: 10.3–56.0), and median progression-free survival was 3.9 months (95% CI: 1.68–7.17). The programmed death-ligand 1 status was unknown. There was no difference in the efficacy of first-line chemotherapy; the objective response rate was 23.5% (n = four of 17) in the nivolumab group versus 32.4% (n = 11 of 34) in the conventional treatment group, and progression-free survival was 3.5 months (95% CI: 1.7–4.4) versus 2.1 months (95% CI: 1.4–4.2), respectively. ConclusionsIn a real-world setting, nivolumab seems to be an effective second-line treatment in patients with advanced LCNEC. Large prospective studies in this setting are still required.

Outcomes for Surgery in Stage IA Large Cell Lung Neuroendocrine Compared With Other Types of Non-Small Cell Lung Cancer: A Propensity Score Matching Study Based on the Surveillance, Epidemiology, and End Results (SEER) Database.

BackgroundPulmonary large cell neuroendocrine cancer (LCNEC) is commonly classified as non-small cell lung cancer (NSCLC). Even for stage I disease, after surgery the survival is always poor, but clinical research on LCNEC is scant and always with unsatisfying sample sizes. Thus, we conduct the first study using the Surveillance, Epidemiology, and End Results (SEER) database to compare survival after surgery between stage I LCNEC and other types of NSCLC.MethodsFrom 2004 to 2016, 473 patients with stage IA LCNEC, 17,669 patients with lung adenocarcinoma (LADC) and 8,475 patients with lung squamous cell cancer (LSCC), all treated with surgery were identified. In addition, 1:1 PSM was used, and overall (OS) and cancer-specific survival (CSS) between groups were compared.ResultsThe 5-year OS rates and CSS rates for LCNEC were 52.5% and 81.5%, respectively. Overall, both OS and CSS were significantly superior for stage IA LADC than LCNEC (for OS: HR 0.636, 95% CI 0.568-0.712; for CSS: HR 0.688, 95% CI 0.561–0.842, LCNEC as reference), while comparable for LSCC with LCNEC (for OS: HR 0.974, 95% CI 0.869–1.091; for CSS: HR 0.907, 95% CI 0.738–1.115). PSM generated 471 pairs when LCNEC was compared with LADC and both OS and CSS were significantly better in LADC than LCNEC (for OS: HR 0.580, 95% CI 0.491–0.686; for CSS: HR 0.602, 95% CI 0.446–0.814). Of note, for the subgroup of patients ≤ 65 years old, HRs for both OS and CSS were lower (for OS: HR 0.470; for CSS: HR 0.482). As for comparison between LCNEC and LSCC, PSM generated 470 pairs. Differently, only CSS was significantly superior in LSCC than LCNEC (HR 0.563, 95% CI 0.392–0.807), while OS was not. Further grouping by age showed only CSS between two groups for patients with age ≤ 65 years old was significantly different (P = 0.006).ConclusionsWe report the first survival comparison after surgery between stage IA LCNEC and other types of NSCLC by SEER database and PSM. Our results demonstrated after surgery, stage IA LCNEC was worse in survival, especially compared to LADC. Extra clinical care should be paid, especially for younger patients. More studies investigating adjuvant therapy are warranted.

Neuroendocrine neoplasms of kidney

The most common anatomical localization of neuroendocrine neoplasms (NEN) are the digestive and bronchopulmonary systems, the total proportion of which exceeds 90 % of cases of this group of tumors. In turn, the remaining cases are represented by extremely rare primary neuroendocrine neoplasms of the head and neck, skin, female genital organs, mammary gland, bladder and kidney. Due to the extremely rare observations and the lack of standardized approaches to the diagnosis and treatment of neuroendocrine neoplasms of the kidneys are of significant clinical interest. The true incidence of NENs of the kidney has not yet been established. We carried out a retrospective analysis of patients undergoing treatment in National Medical Research Centre of Oncology n. a. N. N. Blokhin (Moscow, Russia) from 1992 to 2015. According to the results of a sample of patients among registered 12,013 cases of malignant neoplasms of the kidney with NEN of the kidney, the number of morphologically verified cases of NEN of the kidney was 9 cases (0.07 %). Among the patients included in the study group, the main part was represented by highly differentiated neuroendocrine tumors (7 cases; 77.8 %), small cell cancer (1 case; 11.1 %), large cell neuroendocrine cancer (1 case; 11.1 %). The average age of the patients was 51 years (40–63 years; median – 55 years), among which there were 4 women and 5 men. In addition, we conducted an analysis of the clinical, morphological and molecular biological characteristics of tumors with the study and assessment of the grade Ki-67, which was a determining factor in predicting survival and choosing treatment tactics.

Rare finding of a large cell poorly differentiated neuroendocrine tumor in the colon

A 43 year old female presented to the emergency department for nausea, vomiting and abdominal pain secondary to a bowel obstruction subsequently revealed to be a poorly differentiated large cell neuroendocrine tumor of the colon. After a CT scan showed a mass in the ascending colon with possible metastasis to the right lobe of the liver, an exploratory laparotomy was performed. A hemicolectomy was performed with biopsy of the liver mass. Pathology was consistent with large cell neuroendocrine tumor in all specimens including the liver biopsy, ascending colon, and transverse colon. Although large cell neuroendocrine tumors of the colon are a rare malignancy, they are an important consideration in the workup of multiple colonic masses with metastases, especially in patients presenting with bowel obstruction. The literature on poorly differentiated large cell neuroendocrine cancer and treatment is reviewed. Poorly differentiated large cell neuroendocrine tumor is a rare pathology but should be included in the differential diagnosis in patients presenting with a colon mass and bowel obstruction.

ES04.06 Systemic Treatment of Large Cell Neuroendocrine Cancer

ES04.06 Systemic Treatment of Large Cell Neuroendocrine Cancer

Outcomes for Surgery in Large Cell Lung Neuroendocrine Cancer

IntroductionThere are limited small, single-institution observational studies examining the role of surgery in large cell neuroendocrine cancer (LCNEC). We investigated the outcomes of surgery for stage I to IIIA LCNEC by using the National Cancer Database. MethodsPatients with stage I to IIIA LCNEC were identified in the National Cancer Database (2004–2015) and grouped by treatment: definitive chemoradiation versus surgery. Overall survival, by stage, was the primary outcome. Outcomes of surgical patients were also compared with those of patients with SCLC or other non–small cell histotypes. ResultsA total of 6092 patients met the criteria: 96%, 94%, 75%, and 62% of patients received an operation for stage I, II, IIIA, and cN2 disease, respectively. Complete resection was achieved in at least 85% of patients. The 5-year survival rates for patients undergoing an operation for stage I and II LCNEC were 50% and 45%, respectively. Surgical patients with stage IIIA and N2 disease had 36% and 32% 5-year survival rates, respectively. When compared with stereotactic body radiation in stage I disease and chemoradiation in patients with stage II to IIIA disease, surgery was associated with a survival benefit. Patients with LCNEC who underwent an operation generally experienced worse survival by stage than did those with adenocarcinoma but experienced improved survival compared with patients with SCLC. Perioperative chemotherapy was associated with improved survival for pathologic stage II to IIIA disease. ConclusionsSurgery is associated with reasonable outcomes for stage I to IIA LCNEC, although survival is generally worse than for adenocarcinoma. Surgery should be offered to medically fit patients with both early and locally advanced LCNEC, with guideline-concordant induction or adjuvant therapy.

Neuroendocrine carcinoma of the prostate (review of the literature)

Neuroendocrine neoplasia (NEC) of the prostate gland is a rather rare extrapulmonary neuroendocrine carcinoma and makes up only 0.5 to 1% of all malignant neoplasms of this localization. NEC of the prostate gland is a tumor of epithelial origin, histologically and immunohistochemically identical to analogues in the lungs and digestive system. When stained with hemotoxylin-eosin, neuroendocrine cells cannot always be visualized; they are best recognized by the immunohistochemical method of investigation using specific markers. Currently, a number of neuroendocrine markers are used, the expression of which may indicate a neuroendocrine nature. Androgen neuroendocrine cells themselves are independent and do not cause an increase in the concentration of prostate-specific antigen. Prostate NECs are represented by some histological forms according to WHO classification (2015): 1. Adenocarcinoma with focal neuroendocrine differentiation. 2. Well-differentiated neuroendocrine tumor. 3. Small cell neuroendocrine cancer is a high - grade tumor with high malignant potential. 4. Large cell neuroendocrine cancer is a high - grade tumor. Due to the rarity of NEC of the prostate, a specific algorithm for diagnosis and treatment has not been developed, as a rule, they are similar to methods of other malignant forms of prostate cancer and neuroendocrine tumors.

One Case of Interventional Chemoembolization Treatment of Small Cell Neuroendocrine Cervical Cancer

Small cell neuroendocrine cervical cancer (SCNEC) is some kind of rare malignant cancer of the cervix area. In 1997, according to the research of International Cancer Institute and the American Association of Pathology, the pancreatic endocrine tumors can be sorted into four types by the morphological similarity compared with tumors of the same type in the lung: typical carcinoid, non-typical carcinoid, large cell neuroendocrine cancer, and small cell neuroendocrine cancer, in which the last one is the most previaling. The SCNEC recurs much more often and its distant metastasis is more common in the lungs, brain and liver[1][2]. It characterizes low incidence and few cases, and a retrospective study is commonly used. Without clinical experience, there have been no fair treatment so far. A patient diagnosed as SCNEC A2 period was treated in our hospital, and uterine artery embolization chemotherapy, a new treatment, was taken to her. Consequently, the treatment worked, creating significant surgical conditions for her. Moreover, postoperative examination showed obvious effect of this treatment. The case report is as follows:

Small or Non-Small Cell Lung Cancer Based Therapy for Treatment of Large Cell Neuroendocrine Cancer of The Lung? University of Cincinnati Experience.

Large cell neuroendocrine cancer (LCNEC) of the lung exhibits morphological and immunohistochemical characteristics of both neuroendocrine and large cell carcinomas. No defined optimal therapy has been described for this subset of patients and the question of whether these patients should be treated with non-small cell lung cancer (NSCLC) treatment protocols, according to the National Comprehensive Cancer Network (NCCN) guidelines, or with small cell lung cancer (SCLC) due to histological and clinical similarities is still uncertain. We conducted a retrospective review of patients identified with diagnosis of LCNEC of the lung at the University of Cincinnati Cancer Center from the year 2002 to 2012 to determine which treatment approach resulted in improved outcomes in this rare category of disease. Patients who received chemotherapy whether NSCLC (group A) or SCLC (group B) protocols did not show significant changes in OS (P=0.911). Meanwhile, patients who underwent surgery (group C) had better OS compared to groups A and B (P= 0.027 and 0.024, respectively). This analysis reveals that outcomes for SCLC or NSCLC treatment strategies in LCNEC patients did not result in survival advantages and future research should be addressing it as a separate entity.