Metastatic Large Cell Neuroendocrine Carcinoma Research Articles

A Rare Case of Sinonasal Large Cell Neuroendocrine Carcinoma with Lymph Node Metastasis

Abstract Introduction/Objective Sinonasal carcinomas comprise less than 1% of cancers, and the most common types are squamous cell carcinoma at 51.6% and adenocarcinoma at 12.6%. There are only limited published reports of sinonasal large-cell neuroendocrine carcinoma (LCNEC). This entity has distinguishing immunohistochemical and histomorphologic features; it stains positively for neuroendocrine markers (i.e., synaptophysin and CD56) and histologically has abundant amphophilic cytoplasm with prominent nucleoli. Methods/Case Report We present a 60-year-old female patient who was evaluated for a submandibular neck lump. Computed tomography identified a 3.2 x 1.8 x 1.6 cm enhancing lesion with central necrosis in the right submandibular space, representing either an enlarged necrotic right submandibular lymph node or a neoplasm arising from the right submandibular gland. The pathology of the lymph node biopsy was consistent with metastatic high- grade neuroendocrine carcinoma. The neoplastic cells stained positively for INSM1, CK8/18, CK AE1/3 (subset), TTF- 1, and Ki-67 (50%). Dotatate positron emission tomography showed evidence of focal activity in the right anterior nasal cavity supporting evidence with primary nasal cavity origin. Nasal endoscopy was performed, visualizing an area of necrotic friable tissue. Pathology confirmed the presence of large cell neuroendocrine carcinoma in the right nasal biopsies with metastatic LCNEC in right neck levels 1, 2A, 2B, 3, and 4. The malignant cells on hematoxylin and eosin stain had similar morphology to those in the initial lymph node biopsy, supporting a diagnosis of LCNEC. Results (if a Case Study enter NA) NA Conclusion Sinonasal large-cell neuroendocrine carcinomas are extremely rare. Upon literature search, there have been fewer than ten case reports published of this entity. Furthermore, large-cell neuroendocrine carcinoma behaves aggressively, and diagnosing this entity could result in earlier intervention and better patient outcomes. Highlighting the possibility of this diagnosis could broaden differentials in neoplasms that arise from the nose.

The Effectiveness of Atezolizumab in Metastatic Large Cell Neuroendocrine Carcinoma of the Lungs: Insights from the LANCE Pilot Study.

Large cell neuroendocrine carcinoma (LCNEC) presents significant treatment challenges due to its rarity and limited therapeutic options. The LANCE study was designed to explore the survival benefits of incorporating atezolizumab in chemotherapy for metastatic LCNEC. In this non-randomized study, patients with metastatic LCNEC were prospectively enrolled and assigned to receive either standard chemotherapy plus atezolizumab followed by maintenance with atezolizumab or standard chemotherapy alone. The primary outcomes measured were 12- and 24-month survival rates, progression-free survival (PFS), and overall survival (OS) between the two groups. Of the 22 patients screened, 17 met the inclusion criteria and received either atezolizumab plus platinum-based chemotherapy (n = 10) or chemotherapy alone (n = 7). After a median follow-up of 23.3 months, the 12-month survival rate was 57.1% (95% CI: 32.6-100%) and 14.3% (95% CI: 2.33-87.7%) for the atezolizumab and the chemotherapy-only groups, respectively. The survival benefit for the atezolizumab group was sustained at 24 months (45.7% vs. 14.3%). Overall survival was significantly higher for the atezolizumab group, and PFS was non-significantly associated with the addition of atezolizumab (log-rank p = 0.04 and 0.05, respectively). This pilot study suggests that the addition of atezolizumab to standard platinum-based chemotherapy may provide a substantial survival benefit compared with chemotherapy alone in the first-line treatment of metastatic LCNEC.

Establishment and Validation of Prognostic Nomograms for Patients with Metastatic Pulmonary Large Cell Neuroendocrine Carcinoma.

Metastatic pulmonary large cell neuroendocrine carcinoma (LCNEC) is an aggressive cancer with generally poor outcomes. Effective methods for predicting survival in patients with metastatic LCNEC are needed. This study aimed to identify independent survival predictors and develop nomograms for predicting survival in patients with metastatic LCNEC. We conducted a retrospective analysis using the Surveillance, Epidemiology, and End Results (SEER) database, identifying patients with metastatic LCNEC diagnosed between 2010 and 2017. To find independent predictors of cancer-specific survival (CSS), we performed Cox regression analysis. A nomogram was developed to predict the 6-, 12-, and 18-month CSS rates of patients with metastatic LCNEC. The concordance index (C-index), area under the receiver operating characteristic (ROC) curves (AUC), and calibration curves were adopted with the aim of assessing whether the model can be discriminative and reliable. Decision curve analyses (DCAs) were used to assess the model's utility and benefits from a clinical perspective. This study enrolled a total of 616 patients, of whom 432 were allocated to the training cohort and 184 to the validation cohort. Age, T staging, N staging, metastatic sites, radiotherapy, and chemotherapy were identified as independent prognostic factors for patients with metastatic LCNEC based on multivariable Cox regression analysis results. The nomogram showed strong performance with C-index values of 0.733 and 0.728 for the training and validation cohorts, respectively. ROC curves indicated good predictive performance of the model, with AUC values of 0.796, 0.735, and 0.736 for predicting the 6-, 12-, and 18-month CSS rates of patients with metastatic LCNEC in the training cohort, and 0.795, 0.801, and 0.780 in the validation cohort, respectively. Calibration curves and DCAs confirmed the nomogram's reliability and clinical utility. The new nomogram was developed for predicting CSS in patients with metastatic LCNEC, providing personalized risk evaluation and aiding clinical decision-making.

Incidence, survival comparison, and novel prognostic evaluation approaches for stage iii-iv pulmonary large cell neuroendocrine carcinoma and small cell lung cancer

BackgroundPulmonary large cell neuroendocrine carcinoma (LCNEC) and small cell lung cancer (SCLC) are two types of high-grade neuroendocrine carcinomas of the lung with poor prognosis. LCNEC has not been thoroughly studied due to its rarity, data are also lacking regarding the survival comparison and prognosis analysis of patients with locally advanced or metastatic LCNEC and SCLC.MethodsData of patients with LCNEC, SCLC, and other NSCLC who were diagnosed from 1975 to 2019 were extracted from the Surveillance, Epidemiology and End Results (SEER) database to estimate incidence. Those in stage III-IV and being diagnosed from 2010 to 2015 were utilized further to investigate their clinical characteristics and prognosis. Propensity score matching (PSM) analyses at a ratio of 1:2 was used to compare their survival outcomes. Nomograms of LCNEC and SCLC were established with internal validation, and the nomogram of SCLC was externally validated by 349 patients diagnosed in Cancer hospital, Chinese Academy of Medical Sciences & Peking Union Medical College from January 1, 2012 to December 31, 2018.ResultsThe incidence of LCNEC has been increasing in recent decades, meanwhile that of SCLC and other types of NSCLC were decreasing. A total of 91,635 lung cancer patients, including 785 with LCNEC, 15,776 with SCLC, and 75,074 with other NSCLC were enrolled for further analysis. The survival of stage III-IV LCNEC resembles that of SCLC, and significantly worse than other types of NSCLC before and after PSM analysis. In pretreatment prognostic analysis, age, T stage, N stage, M stage, bone metastasis, liver metastasis, and brain metastasis were found to be associated with the survival of both LCNEC and SCLC, besides sex, bilaterality, and lung metastasis were additional prognostic factors for SCLC. Two nomograms and convenient online tools respectively for LCNEC and SCLC were established accordingly with favorable predicting accuracy of < 1-year, < 2-year, < 3-year survival probabilities. In external validation of the SCLC nomogram with a Chinese cohort, the AUCs of 1-year, 2-year and 3-year ROC were 0.652, 0.669, and 0.750, respectively. All the results of 1-, 2-, 3- year variable-dependent ROC curves verified the superior prognostic value of our nomograms for LCNEC and SCLC over the traditional T/N/M staging system.ConclusionsBased on large sample-based cohort, we compared the epidemiological trends and survival outcomes between locally advanced or metastatic LCNEC, SCLC, and other NSCLC. Furthermore, two prognostic evaluation approaches respectively for LCNEC and SCLC might present as practical tools for clinicians to predict the survival outcome of these patients and facilitate risk stratification.

ODP361 A Case of Panhypopituitarism in the Setting of Metastatic Large Cell Neuroendocrine Carcinoma

Abstract Introduction Metastasis to the pituitary gland is an uncommon cause of panhypopituitarism. The pituitary gland is an infrequent site overall for metastasis, with breast and lung cancer as most often found primary sites. Large cell neuroendocrine carcinoma is a rare form of lung cancer, and while metastasis to brain is not uncommon is this form of cancer, metastasis to the pituitary gland has rarely been reported. Clinical Case Patient was a 64 year old male with history of homelessness and substance use who had repeated hospitalizations for right sided pneumonia. Eventually bronchoscopy was performed, and tissue obtained via biopsy revealed a high-grade large cell neuroendocrine carcinoma. Initial brain imaging noted extensive brain metastases with numerous enhancing lesions in the cortex, as well as a 13×9×8 mm suprasellar mass abutting the optic chiasm. Thickening of the infundibulum was also noted. Lab testing demonstrated hypopituitarism with free thyroxine 0.52 (reference 0.93-1.7) ng/dL, thyroid-stimulating hormone 0.11 (2.7-4.2) ulU/mL, sodium 139 (135-147) mEq/L, total testosterone &amp;lt;0.1 (2.8-8) ng/ml, follicular-stimulating hormone 0.4 mlU/ml, lutenizing hormone &amp;lt;0.10 mlU/ml, prolactin 25.7 (4-15.2) ng/ml, cortisol &amp;lt;2 (3-12) ug/dL, and adrenocorticotropic hormone &amp;lt;5 (6-50) pg/mL. Diabetes insipidus was not present. Metastatic cancer was treated with dexamethasone and atezolizumab plus carboplatin and etoposide. Panhypopituitarism was treated with levothyroxine, testosterone replacement, and glucocorticoid replacement. One month later, patient represented with shortness of breath and headache. Repeat brain imaging showed an enhancing sellar mass measuring 21×15×11 mm extending superiorly to involve the pituitary stalk and hypothalamus. The extending suprasellar mass was noted to have enhancement and characteristics akin to remainder of brain metastases. The patient passed away from complications of metastatic carcinoma about three months after initial biopsy proven diagnosis. Conclusion This patient developed extensive brain metastases from pulmonary large cell neuroendocrine carcinoma, which included a metastasis in the sella resulting in panhypopituitarism. While pituitary metastases from primary cancer are very rare events (with lung and breast carcinoma the most frequent sources), only a single case report exists describing a pituitary metastasis from a large cell neuroendocrine carcinoma. This case is also an important reminder to consider the pretreatment anatomy of the sella in patients subsequently exposed to immunomodulating chemotherapy, as a mass lesion seen during treatment may represent a preexisting metastasis rather than treatment-induced hypophysitis. Presentation: No date and time listed

Néoplasies neuro-endocrines broncho-pulmonaires primitives : tumeurs carcinoïdes et carcinomes neuro-endocrines à grandes cellules

Primary pulmonary neuroendocrine neoplasms comprise several distinct clinical entities, corresponding to four main histological subtypes: well differentiated neuroendocrine tumors including typical carcinoid tumors, of low grade malignancy and atypical carcinoids of intermediate grade malignancy; and neuro-endocrine carcinomas with either small or large cells, of high grade malignancy.The pre-treatment workup of carcinoid tumors relies on specific recommendations. Any clinical suspicion of an associated functional syndrome must be confirmed by the appropriate blood dosages.In case of metastatic carcinoid tumor, management relies on the control of a possible secretory syndrome, in addition to the oncological treatment, based on the evaluation of tumor progression, with several opportunities: close follow-up, local treatment of metastases, treatment with somatostatin analogues, everolimus, or chemotherapy for tumor with high aggressiveness. Peptide receptor radionuclide therapy with 177Lu-DOTATATE in patients with somatostatin receptor-expressing neuroendocrine tumors is an interesting option not yet validated for routine use.In case of advanced, metastatic large-cell neuroendocrine carcinoma, platinum and etoposide combination is generally used in front line. However, for tumors that express RB or harbor KRAS or STK11 mutations, platinum and gemcitabine or platinum and taxane combination may be used. No established second line is available, but treatments used in NSCLC can be suggested, except pemetrexed.1877-1203/© 2022 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Platinum Doublet plus Atezolizumab as First-line Treatment in Metastatic Large Cell Neuroendocrine Carcinoma: A Single Institution Experience

Background Large Cell Neuroendocrine Carcinoma of the Lung (L-LCNEC) is a rare type of neuroendocrine lung cancer that is increasingly diagnosed. However, the optimal management regarding the advanced stage is unclear. The purpose of this article is to present and compare our experience when L-LCNEC is treated as Small Cell Lung Cancer (SCLC). Patients and Methods Overall, eight cases of L-LCNEC were included. We retrospectively reviewed medical files and reports by accessing the Institution's Data of patients diagnosed with L-LCNEC from April 2019 until December 2020 and evaluated their response to the combination of Platinum – Etoposide – Atezolizumab as first-line chemotherapy. Results The overall observed response rate (ORR) of 75%. The median PFS was 6.85 months. The median response duration was 5.5 months. Conclusions Comparing our findings with other retrospective and prospective studies, it seems that the systematic treatment of choice and management in L-LCNEC of the lung should be that of a small cell carcinoma of the lung.

Néoplasies neuro-endocrines broncho-pulmonaires primitives : tumeurs carcinoïdes et carcinomes neuro-endocrines à grandes cellules: Primary pulmonary neuroendocrine neoplasms : carcinoid tumors and large-cell neuro-endocrine carcinomas

Primary pulmonary neuroendocrine neoplasms comprise several distinct clinical entities, corresponding to four main subtypes: well differentiated neuroendocrine tumors including typical carcinoid tumors, of low grade malignancy and atypical carcinoids of intermediate grade; neuro-endocrine carcinomas with either small or large cells, which are high grade, frequent malignancy.The pre-treatment workup of carcinoid tumors is based on specific recommendations. Any clinical suspicion of an associated functional syndrome must be confirmed by the appropriate blood dosages.In case of metastatic carcinoid tumor, management relies on the control of a possible secretory syndrome, in addition to the oncological treatment, based on the evaluation of tumor progression, with several opportunities: close follow-up, local treatment of metastases, treatment with somatostatin analogues, everolimus, or chemotherapy for tumor with high aggressiveness. Peptide receptor radionuclide therapy with 177Lu-DOTATATE in patients with somatostatin receptor-expressing neuroendocrine tumors is an interesting option not yet validated for routine use.In case of advanced, metastatic large-cell neuroendocrine carcinoma, platinum and etoposide combination is generally used in front line. No established second line is available. Results of the IFCT-FFCD-GERCOR “NIPINEC trial” evaluating nivolumab, with or without ipilimumab in the second- and third-line setting are awaiting. Molecular analysis of a panel of oncogenic alterations could guide therapeutic decision.© 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.

S1455 A Rare Case of Poorly Differentiated Metastatic Extra-Pulmonary Neuroendocrine Tumor in an HIV Patient

INTRODUCTION: HIV infected individuals have an increased risk of malignancies such as Kaposi sarcoma, primary central nervous system lymphoma, non-Hodgkin lymphom, and cervical cancer. The incidence of non-AIDSdefining tumors such as Neuroendocrine Tumor (NET) has not been well reported in the literature. Majority of NETs occur in the gastrointestinal tract (almost 68%) and bronchopulmonary tree (about 25%). Of the GI NETs, most are in the small intestine with less than 1% of pancreatic origin. We present an HIV patient with primary pancreatic NET with metastasis to the liver. CASE DESCRIPTION/METHODS: A 56-year-old African American male with history of HIV currently on antiretrovirals presented with complaints of non-radiating chest pain, shortness of breath, back pain, dizziness, night sweats, nausea, constipation, and recent weight loss. Patient is a current non-smoker with 30 pack year history, no recent travel or sick contacts. Initial workup, including CBC, CMP, EKG, and chest x-ray on admission were unremarkable. Physical exam and vital signs were within normal limits; however, due to the presenting symptoms, CTA of the chest was obtained revealing an incidental finding of a hypodense soft tissue mass highly suspicious for lymphoma. Follow up CT Abdomen and Pelvis with contrast revealed retroperitoneal and periportal lymphadenopathy along with a 3.7 cm Liver mass, suggestive of lymphoma with soft tissue metastasis. In view of these findings the primary working diagnosis was HIV associated lymphoma. However, CT guided liver and lymph node biopsy pathology favored metastatic large cell neuroendocrine carcinoma, most probable primary in pancreas. DISCUSSION: Even though there are malignancies commonly associated with HIV and AIDS, it is important to keep a broad differential when working up a patient with HIV. The incidence of ADC decreased 2-3 folds since 1998 while NADC increased in incidence but no variance of standardized in the same time frame. This has been attributed to the introduction of combination antiretroviral therapies that increased HIV patients life expectancy and allowing them to be at the same risk of developing age-related cancers as the general population. NET in HIV positive patients in sites other than lungs and skin has not been well characterized. Previous study has shown a correlation between Merkel Cell carcinoma and concurrent HIV infection, and it is unclear if our pancreatic cancer is sporatic or associated with HIV infection.

Tumeurs neuro-endocrines broncho-pulmonaires primitives : tumeurs carcinoïdes et carcinomes neuro-endocrines à grandes cellules: Primary pulmonary neuroendocrine tumors: Carcinoid tumors and large-cell neuro-endocrine carcinomas

AbstractPrimary pulmonary neuroendocrine tumors comprise several distinct clinical entities, corresponding to four main subtypes: typical carcinoid tumors, of low grade malignancy; atypical carcinoids of intermediate grade; neuro-endocrine carcinomas with either small or large cells, which are high grade, frequent malignancy.The pre-treatment workup of carcinoid tumors is based on specific recommendations. Any clinical suspicion of an associated functional syndrome must be confirmed by the appropriate blood dosages.In case of metastatic carcinoid tumor, management relies on the control of a possible secretory syndrome by somatostatin analogues, in addition to the oncological treatment, based on the evaluation of tumor progression, with several opportunities: close follow-up, local treatment of metastases, treatment with somatostatin analogues, everolimus, or chemotherapy for tumor with high aggressiveness.In case of advanced, metastatic large-cell neuroendocrine carcinoma, molecular analysis of a panel of oncogenic alterations could guide the chemotherapy strategy; platinum and etoposide combination has historically been used. In the second line, in the absence of any therapeutic standard, the IFCT-FFCD-GERCOR “NIPINEC trial” is recruiting in France in and aims at evaluating nivolumab, with or without ipilimumab in the second- and third-line setting.© 2020 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Tumeurs neuro-endocrines broncho-pulmonaires primitives: tumeurs carcinoïdes et carcinomes neuro-endocrines à grandes cellules

Primary pulmonary neuroendocrine tumors comprise several distinct clinical entities, corresponding to four main subtypes: typical carcinoid tumors, of low grade malignancy; atypical carcinoids of intermediate grade; neuro-endocrine carcinomas with either small or large cells, which are high grade, frequent malignancy.The pre-treatment workup of carcinoid tumors is based on specific recommendations. Any clinical suspicion of an associated functional syndrome must be confirmed by the appropriate blood dosages.In case of metastatic carcinoid tumor, management relies on the control of a possible secretory syndrome by somatostatin analogues, in addition to the oncological treatment, based on the evaluation of tumor progression, with several opportunities: close follow-up, local treatment of metastases, treatment with somatostatin analogues, everolimus, or chemotherapy for tumor with high aggressiveness.In case of advanced, metastatic large-cell neuroendocrine carcinoma, molecular analysis of a panel of oncogenic alterations could guide the chemotherapy strategy; platinum and etoposide combination has historically been used. In the second line, in the absence of any therapeutic standard, the IFCT-FFCD-GERCOR “NIPINEC trial” is recruiting in France in and aims at evaluating nivolumab, with or without ipilimumab in the second- and third-line setting.

Abstract 487: A high percentage of LCNEC shows DLL3 expression in association with molecular subtypes and neuroendocrine markers

Abstract Background Pulmonary large cell neuroendocrine carcinoma (LCNEC) can be subdivided in two types: the co-mutated TP53 and RB1 subtype, and the TP53 and STK11/KEAP1 mutated subtype (Derks et al. Clin Cancer Res 2018; J Thorac Oncol 2018). DLL3 is a member of the Notch ligand family and a possible treatment target for neuroendocrine carcinoma. We investigated DLL3 and NE marker expression in mutational subtypes of metastatic LCNEC. Methods Immunohistochemical (IHC) analysis for DLL3 (clone SC16.65) was performed on 94 pathological reviewed pretreatment stage IV LCNEC. Samples were scored positive if ≥1% tumor cells showed cytoplasmic or dotlike DLL3 immunostaining. Also an H-score was calculated by multiplying intensity by percentage of positive cells. Targeted next generation sequencing (TP53, RB1, STK11, KEAP1) could be performed in 66 patients. Results DLL3 was expressed in 70/94 (75%) LCNEC, 56 of which showed cytoplasmic immunostaining. 37/70 (53%) samples had an H-score&amp;gt;100. DLL3 staining was more often seen in STK11 and/or KEAP1 mutated LCNEC (13/14;93%) than in tumors with wildtype STK11/KEAP1 (36/52;69%) (trend;p=0.093). In addition, DLL3 positivity was associated with expression of ≥2 NE-markers (64/79 LCNEC (81%) vs 3/8 (37%) tumors with &amp;lt;2 NE-markers; p=0.014). Conclusions A high percentage (75%) of stage IV LCNEC shows cytoplasmatic DLL3 epression in association with NE markers, half of which with H-scores&amp;gt;100. Interestingly, DLL3 positivity was observed in almost all STK11/KEAP1 mutated LCNEC, which is in agreement with recent data (George et al. Nat Commun 2018). It thus might be worthwhile to investigate the efficacy of DLL3 targeted therapy in LCNEC. Citation Format: Ernst-Jan M. Speel, Bregtje C. Hermans, Jules L. Derks, Erik Thunnissen, Robert Jan van Suylen, Michael A. den Bakker, Harry J. Groen, Egbert F. Smit, Ronald A. Damhuis, Esther C. van den Broek, Cecile M. Stallinga, Guido M. Roemen, Anne-Marie C. Dingemans. A high percentage of LCNEC shows DLL3 expression in association with molecular subtypes and neuroendocrine markers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 487.

Prevalence and prognostic value of PD-L1 expression in molecular subtypes of metastatic large cell neuroendocrine carcinoma (LCNEC)

BackgroundPulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare tumor with high mutational burden. Two subtypes of LCNEC are recognized, the co-mutated TP53 and RB1 group and the TP53 and STK11/KEAP1 group. We investigated PD-L1 and CD8 expression in a well characterized stage IV LCNEC cohort and compared expression in the two subtypes. MethodsImmunohistochemical (IHC) analysis for PD-L1 and CD8 was performed on pathological reviewed pretreatment tumor samples for 148 stage IV LCNEC. Data about targeted next generation sequencing (TNGS) (TP53, RB1, STK11, KEAP1) and IHC for RB1 were available for most tumors. IHC staining for PD-L1 (DAKO 28-8) was performed and scored positive if tumors showed ≥1% membranous staining. CD8 was scored for intra-tumor T-cells and stromal cells. ResultsPD-L1 IHC expression data could be generated in 98/148 confirmed LCNEC samples along with RB1 IHC (n = 97) of which 77 passed quality control for TNGS. PD-L1 expression was positive in 16/98 cases (16%); 5 (5%) with ≥50%. PD-L1 expression was equal in RB1 mutated and RB1 wildtype tumors. None of STK11 mutated tumors (n = 7) expressed PD-L1. PD-L1 expression was correlated with superior overall survival (OS), hazard ratio 0.55 ((95% Confidence Interval 0.31-0.96), p = 0.038). Intra-tumor CD8 was associated with PD-L1 expression (p = 0.021) and stromal and intra-tumor CD8 were correlated with improved OS (p = 0.037 and p = 0.026 respectively). ConclusionsPD-L1 expression was positive in 16% of stage IV LCNEC tumors. This was independent of molecular subtype but associated with CD8 expression. In LCNEC patients with PD-L1 and/or CD8 expression superior OS was observed.

Metastatic large cell neuroendocrine carcinoma of larynx: Individualizing tumor biology by dual tracer positron emission tomography/computed tomography (68Ga-DOTATATE and 18F-fluorodeoxyglucose) molecular imaging and disease stabilization following 177Lu-DOTATATE peptide receptor radionuclide therapy after initial progression on chemoradiotherapy

Metastatic large cell neuroendocrine carcinoma of larynx: Individualizing tumor biology by dual tracer positron emission tomography/computed tomography (⁶⁸Ga-DOTATATE and ¹⁸F-fluorodeoxyglucose) molecular imaging and disease stabilization following ¹⁷⁷Lu-DOTATATE peptide receptor radionuclide therapy after initial progression on chemoradiotherapy

1813P - Prevalence and prognostic value of PD-L1 expression in molecular subtypes of metastatic large cell neuroendocrine carcinoma (LCNEC)

1813P - Prevalence and prognostic value of PD-L1 expression in molecular subtypes of metastatic large cell neuroendocrine carcinoma (LCNEC)

Tumeurs neuro-endocrines broncho-pulmonaires primitives : tumeurs carcinoïdes, carcinomes neuro-endocrines à grandes cellules

Primary pulmonary neuroendocrine tumors comprise several distinct clinical entities, corresponding to four main subtypes : typical carcinoid tumors, of low grade malignancy ; atypical carcinoids of intermediate grade ; neuro-endocrine carcinomas with either small or large cells, which are high grade, frequent malignancy.The pre-treatment workup of carcinoid tumors is based on specific recommendations. Any clinical suspicion of an associated functional syndrome must be confirmed by the appropriate blood dosages.In case of metastatic carcinoid tumor, management relies on the control of a possible secretory syndrome by somatostatin analogues, in addition to the oncological treatment, based on the evaluation of tumor progression, with several opportunities : close follow-up, local treatment of metastases, treatment with somatostatin analogues, everolimus, or chemotherapy for tumor with high aggressiveness.In case of advanced, metastatic large-cell neuroendocrine carcinoma, molecular analysis of a panel of oncogenic alterations could guide the chemotherapy strategy ; platinum and etoposide combination has historically been used. In the second line, in the absence of any therapeutic standard, the IFCT-FFCD-GERCOR NIPINEC trial is opening in France in 2018 and aims at evaluating nivolumab, with or without ipilimumab in the second- and third-line setting.

Large Cell Neuroendocrine Carcinoma of the Larynx: A Case Report and Review of Literature

Laryngeal neuroendocrine carcinomas (LNEC) constitute <1% of all tumours originating from the larynx and are believed to originate from pluripotential stem cells located in the submucosa of the larynx. It is hard to estimate the true incidence of large-cell neuroendocrine carcinoma (LCNEC) because the WHO classification does not make a distinction between atypical carcinoid tumors and large-cell neuroendocrine carcinoma. In the current classification, laryngeal LCNEC is considered synonymous with atypical carcinoid/moderately-differentiated (Grade II) neuroendocrine carcinoma. This distinction is clinically important as the clinical behavior and response to treatment differs greatly between subtypes. We report a rare case of metastatic LCNEC of subglottic region of larynx who is treated with chemotherapy and radiotherapy and a review of literature on the diagnosis and treatment of these tumors is presented.

Chemotherapy for pulmonary large cell neuroendocrine carcinomas: does the regimen matter?

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is rare. Chemotherapy for metastatic LCNEC ranges from small cell lung carcinoma (SCLC) regimens to nonsmall cell lung carcinoma (NSCLC) chemotherapy regimens. We analysed outcomes of chemotherapy treatments for LCNEC.The Netherlands Cancer Registry and Netherlands Pathology Registry (PALGA) were searched for patients with stage IV chemotherapy-treated LCNEC (2003–2012). For 207 patients, histology slides were available for pathology panel review. First-line platinum-based combined chemotherapy was clustered as “NSCLC-t”, comprising gemcitabine, docetaxel, paclitaxel or vinorelbine; “NSCLC-pt”, with pemetrexed treatment only; and “SCLC-t”, consisting of etoposide chemotherapy.A panel review diagnosis of LCNEC was established in 128 out of 207 patients. NSCLC-t chemotherapy was administered in 46% (n=60), NSCLC-pt in 16% (n=20) and SCLC-t in 38% (n=48) of the patients. The median (95% CI) overall survival for NSCLC-t chemotherapy was 8.5 (7.0–9.9) months, significantly longer than patients treated with NSCLC-pt, with a median survival of 5.9 (5.0–6.9) months (hazard ratio 2.51, 95% CI 1.39–4.52; p=0.002) and patients treated with SCLC-t chemotherapy, with a median survival of 6.7 (5.0–8.5) months (hazard ratio 1.66, 95% CI 1.08–2.56; p=0.020).In patients with LCNEC, NSCLC-t chemotherapy results in longer overall survival compared to NSCLC-pt and SCLC-t chemotherapy.

Long-term Survival of Large Cell Neuroendocrine Lung Carcinoma with Bony Metastases: A Case of Immunoprotectivity?

Large cell neuroendocrine carcinoma (LCNEC) is a rare, highly malignant neoplasm with a dismal prognosis. The majority of patients will present with metastatic disease with a median overall survival of 6 months for this group. We present a case of metastatic LCNEC to the pelvis with a 10 year survival after tumor resection, radiation, and chemotherapy. We hypothesize that his survival and cancer stability are the result of an immune response brought on by a sub-acute turned chronic wound infection. After adjuvant therapies, he remained disease-free for 4 years until a recurrence in his lung and new metastases to his spine, which were treated with radiation. He remained disease-free for an additional 6 years, during which time, he discovered to have a chronic infection of his right femur with Staphylococcus Lugdunensis. To the best of our knowledge, this is the first long-term survivor of LCNEC with bony metastases.

A marked response to icotinib in a patient with large cell neuroendocrine carcinoma harboring an EGFR mutation: A case report.

The present study reports the case of an 84-year-old male with primary pulmonary large cell neuroendocrine carcinoma (LCNEC) harboring an epidermal growth factor receptor (EGFR) gene mutation that exhibited a long-lasting response to the EGFR-tyrosine kinase inhibitor (EGFR-TKI) icotinib. The patient had an extensive smoking history, a poor performance status, and presented with an irregular mass in the middle lobe of the right lung on computed tomography (CT) and an enlarged left supraclavicular lymph node on physical examination. Right middle lobe bronchial brushing during fiberoptic bronchoscopy identified poorly-differentiated cancer cells. The left supraclavicular lymph node was biopsied and a diagnosis of metastatic LCNEC was determined. Furthermore, an EGFR exon 19 deletion was identified by DNA sequencing. Following diagnosis, icotinib was administered at a dose of 125 mg three times a day. Chest CT scans were performed after 1 month of treatment, which indicated that the tumor was in partial remission. This marked response to icotinib lasted for 8 months. Thus, the present case illustrates the possibility of identifying EGFR mutations in LCNEC and indicates that EGFR-tyrosine kinase inhibitors may be an alternative treatment strategy for patients with LCNEC harboring activating EGFR mutations.