scholarly journals Large cell neuroendocrine carcinoma with a solitary brain metastasis and low Ki-67: a unique subtype

2019 ◽  
Vol 8 (12) ◽  
pp. 1600-1606 ◽  
Author(s):  
B C M Hermans ◽  
J L Derks ◽  
H J M Groen ◽  
J A Stigt ◽  
R J van Suylen ◽  
...  
Keyword(s):  
Brain Metastasis ◽  
Small Cell Lung Carcinoma ◽  
Stage Iv ◽  
Large Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
Ki 67 ◽  
Cell Lung Carcinoma ◽  
Solitary Brain Metastasis

Introduction Stage IV large cell neuroendocrine carcinoma (LCNEC) of the lung generally presents as disseminated and aggressive disease with a Ki-67 proliferation index (PI) 40–80%. LCNEC can be subdivided in two main subtypes: the first harboring TP53/RB1 mutations (small-cell lung carcinoma (SCLC)-like), the second with mutations in TP53 and STK11/KEAP1 (non-small-cell lung carcinoma (NSCLC)-like). Here we evaluated 11 LCNEC patients with only a solitary brain metastasis and evaluate phenotype, genotype and follow-up. Methods Eleven LCNEC patients with solitary brain metastases were analyzed. Clinical characteristics and survival data were retrieved from medical records. Pathological analysis included histomorphological analysis, immunohistochemistry (pRB and Ki-67 PI) and next-generation sequencing (TP53, RB1, STK11, KEAP1 and MEN1). Results All patients had N0 or N1 disease. Median overall survival (OS) was 12 months (95% confidence interval (CI) 5.5–18.5 months). Mean Ki-67 PI was 59% (range 15–100%). In 6/11 LCNEC Ki-67 PI was ≤40%. OS was longer for Ki-67 ≤40% compared to >40% (17 months (95% CI 11–23 months) vs 5 months (95% CI 0.7–9 months), P = 0.007). Two patients were still alive at follow-up after 86 and 103 months, both had Ki-67 ≤40%. 8/11 patients could be subclassified, and both SCLC-like (n = 6) and NSCLC-like (n = 2) subtypes were present. No MEN1 mutation was found. Conclusion Stage IV LCNEC with a solitary brain metastasis and N0/N1 disease show in the majority of cases Ki-67 PI ≤40% and prolonged survival, distinguishing them from general LCNEC. This unique subgroup can be both of the SCLC-like and NSCLC-like subtype.

Genetic subtypes of large cell neuroendocrine carcinoma (LCNEC) to predict response to chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 9061-9061 ◽  
Author(s):  
Jules Derks ◽  
Noémie Leblay ◽  
Robert Jan van Suylen ◽  
Erik Thunnissen ◽  
Michael den Bakker ◽  
...  
Keyword(s):  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Large Cell ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Netherlands Cancer Registry ◽  
Response To Chemotherapy

9061 Background: To treat LCNEC with non-small cell lung carcinoma type chemotherapy (NSCLC-ct, i.e. gemcitabine/taxanes or pemetrexed) or small cell lung carcinoma type (SCLC-ct, i.e. platinum-etoposide) is subject of debate. Molecular studies have identified two mutually exclusive subtypes in LCNEC, the co-mutated TP53 and RB1and the STK11/ KEAP1 (predominantly RB1 wildtype(wt)) group. We investigated if overall survival (OS) and progression free survival (PFS) correlates with targeted next-generation sequencing (TNGS) results in LCNEC treated with NSCLC-ct or SCLC-ct. Methods: For this population based retrospective cohort study all diagnoses of stage IV ct treated high grade neuroendocrine carcinomas (NEC, not being SCLC) were retrieved from the Netherlands Cancer Registry and Pathology Registry (PALGA) (2003-2012). Panel-consensus pathology revision of original tumor slides was performed on (N = 230) and TNGS for genes TP53, RB1, STK11 and KEAP1 analyzed with a multi-sample variant caller (Needlestack). Results: LCNEC was consensus diagnosed in 146/230 and 77 passed quality control for TNGS. Mean coverage was 2832x, a mutation(mt) in TP53 was present in 87%, RB1mt in 46%, STK11mt in 13% and KEAP1mt in 18% of sequenced LCNEC. RB1 was co-altered with TP53 in 94% of LCNEC; mutually exclusive to STK11mt (100%) but not KEAP1mt (57%). NSCLC-ct or SCLC-ct was specified in 92% of patients and RB1wt LCNEC treated with NSCLC-ct (n = 22) showed a trend to better OS compared to SCLC-ct (n = 13) (8.5 months (95% confidence interval (CI): [6.3-10.6]) vs. 5.8 [5.5-6.1] months, p = 0.055). Due to reported resistance in NECs we analyzed NSCLC-ct without pemetrexed-ct; OS was significantly longer for NSCLC-ct (n = 15) compared to SCLC-ct (9.6 [7.7-11.6] vs. 5.8 [5.5-6.1] months, p = 0.026). PFS of RB1wt NSCLC-ct treated patients was significantly longer than SCLC-ct (p = 0.044), without pemetrexed (p = 0.018). In patients with RB1mt LCNEC OS/PFS was not significantly different for NSCLC-ct vs. SCLC-ct. Conclusions: In LCNEC with RB1wt, NSCLC-ct correlates with a more favorable outcome compared to SCLC-ct. However, RB1mt LCNEC treated with NSCLC-ct do similarly worse as SCLC-ct. Prospective studies should be initiated.

scholarly journals Differential development of large-cell neuroendocrine or small-cell lung carcinoma upon inactivation of 4 tumor suppressor genes

2019 ◽  
Vol 116 (44) ◽  
pp. 22300-22306 ◽  
Author(s):  
Sara Lázaro ◽  
Miriam Pérez-Crespo ◽  
Corina Lorz ◽  
Alejandra Bernardini ◽  
Marta Oteo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Large Cell ◽  
Small Cell ◽  
Imaging Method ◽  
Cancer Type ◽  
High Grade ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma

High-grade neuroendocrine lung malignancies (large-cell neuroendocrine cell carcinoma, LCNEC, and small-cell lung carcinoma, SCLC) are among the most deadly lung cancer conditions with no optimal clinical management. The biological relationships between SCLC and LCNEC are still largely unknown and a current matter of debate as growing molecular data reveal high heterogeneity with potential therapeutic consequences. Here we describe murine models of high-grade neuroendocrine lung carcinomas generated by the loss of 4 tumor suppressors. In an Rbl1-null background, deletion of Rb1, Pten, and Trp53 floxed alleles after Ad-CMVcre infection in a wide variety of lung epithelial cells produces LCNEC. Meanwhile, inactivation of these genes using Ad-K5cre in basal cells leads to the development of SCLC, thus differentially influencing the lung cancer type developed. So far, a defined model of LCNEC has not been reported. Molecular and transcriptomic analyses of both models revealed strong similarities to their human counterparts. In addition, a 68Ga-DOTATOC–based molecular-imaging method provides a tool for detection and monitoring the progression of the cancer. These data offer insight into the biology of SCLC and LCNEC, providing a useful framework for development of compounds and preclinical investigations in accurate immunocompetent models.

Real-world evidence in the treatment of metastatic non-small cell lung cancer in a single institution of Colombia in the period August 2015 to August 2018.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18204-e18204
Author(s):  
Luis Eduardo Pino ◽  
Aylen Vanessa Ospina Serrano ◽  
Ivan Camilo Triana
Keyword(s):  
Lung Cancer ◽  
Clinical Characteristics ◽  
Egfr Mutation ◽  
Small Cell Lung Carcinoma ◽  
Target Therapy ◽  
Stage Iv ◽  
Small Cell ◽  
Small Cell Lung ◽  
Alk Rearrangement ◽  
Cell Lung Carcinoma

e18204 Background: In Colombia, lung cancer is the first cause of mortality. However, there is a large gap in terms of the information available regarding the characteristics and survival of these patients in the country. Methods: This is an observational, descriptive study of a cohort of patients with stage IV non-small cell lung carcinoma who initiated medical treatment at Fundación Santa Fe de Bogotá, a high complexity hospital. We analyzed clinical characteristics, oncogenic addiction expression, PDL1 expression, treatments, progression free survival (PFS), overall survival (OSm) and treatment related complications. Results: Twenty-six patients were included during the 3 years. The OSm for all the cohort was 19.6 months(m). In the group without PDL-1 expression and negative for oncogenic addiction that received treatment with chemotherapy the OSm was 16.9m and the PFS 9.6m. The OSm for the group with EGFR mutation that received target therapy was 24,7m and the PFS 13.11m. The patients with ALK rearrangement treated with target therapy had an OSm 17m and PFS 5m. The group with expression greater than 50% for PDL-1 that received only immunotherapy OSm was 9.5m and PFS 9m, and in the group with expression for PDL-1 between 1-49% the median OSm and PFS has not been reached. In relation with grade 3 toxicity, 7% of patients that received chemotherapy had kidney failure, 7% emesis and 15% hyporexia. Patients that received target therapy 9% had diarrhea and 9% hepatotoxicity. 9% of patients with bevacizumab presented bleeding and 8% of patients with immunotherapy had autoimmune colitis, in all these cases the medication was suspended. Hypothyroidism was the most frequent complication with the immunotherapy, and it was resolved with substitution therapy. Conclusions: Clinical characteristics and outcomes of this cohort were similar to other lung cancer patients series. Factors like cigarette, nutritional status and ECOG were no significant in the survival. 34,6% of patients had EGFR mutation and 7% had ALK rearrangements. Related to PDL1 we found 26% expresser patients. The highest OS and PFS was for the group with the EGFR mutation and for the group with PDL-1 expression between 1-49%.

Sign in / Sign up

Export Citation Format

Share Document