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

2017 ◽  
Vol 49 (6) ◽  
pp. 1601838 ◽  
Author(s):  
Jules L. Derks ◽  
Robert Jan van Suylen ◽  
Erik Thunnissen ◽  
Michael A. den Bakker ◽  
Harry J. Groen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Median Survival ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Stage Iv ◽  
Large Cell ◽  
Hazard Ratio ◽  
Cell Lung Carcinoma ◽  
Netherlands Cancer Registry ◽  
Panel Review

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.

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.

scholarly journals Clinical features of large cell neuroendocrine carcinoma: a population-based overview

2015 ◽  
Vol 47 (2) ◽  
pp. 615-624 ◽  
Author(s):  
Jules L. Derks ◽  
Lizza E. Hendriks ◽  
Wieneke A. Buikhuisen ◽  
Harry J.M. Groen ◽  
Erik Thunnissen ◽  
...  
Keyword(s):  
The Netherlands ◽  
Cancer Registry ◽  
Neuroendocrine Carcinoma ◽  
Early Stage ◽  
Small Cell Lung Carcinoma ◽  
Large Cell ◽  
Large Cell Neuroendocrine Carcinoma ◽  
Stage I ◽  
Cell Lung Carcinoma ◽  
Netherlands Cancer Registry

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is an orphan disease and few data are available on its clinical characteristics. Therefore, we analysed LCNEC registered in the Netherlands Cancer Registry, and compared data with small cell lung carcinoma (SCLC), squamous cell carcinoma (SqCC) and adenocarcinoma (AdC).Histologically confirmed LCNEC (n=952), SCLC (n=11 844), SqCC (n=19 633) and AdC (n=24 253) cases were selected from the Netherlands Cancer Registry (2003–2012). Patient characteristics, metastasis at diagnosis (2006 or later), overall survival (OS) including multivariate Cox models and first-line treatment were compared for stage I–II, III and IV disease.The number of LCNEC cases increased from 56 patients in 2003 to 143 in 2012, accounting for 0.9% of all lung cancers. Stage IV LCNEC patients (n=383) commonly had metastasis in the liver (47%), bone (32%) and brain (23%), resembling SCLC. Median OS (95% CI) of stage I–II, III and IV LCNEC patients was 32.4 (22.0–42.9), 12.6 (10.3–15.0) and 4.0 (3.5–4.6) months, respectively. Multivariate-adjusted OS of LCNEC patients resembled that of SCLC patients, and was poorer than those of SqCC and AdC patients. However, frequency of surgical resection and adjuvant chemotherapy resembled SqCC and AdC more than SCLC.Diagnosis of LCNEC has increased in recent years. The metastatic pattern of LCNEC resembles SCLC as does the OS. However, early-stage treatment strategies seem more comparable to those of SqCC and AdC.

Lymphatic vessel density is not associated with lymph node metastasis or survival in non-small cell lung carcinoma (NSCLC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18008-18008
Author(s):  
V. M. Villaflor ◽  
L. Faoro ◽  
J. Hutto ◽  
J. Varalakshmi ◽  
K. Suzue ◽  
...  
Keyword(s):  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Median Survival ◽  
Lung Carcinoma ◽  
Small Cell Lung Carcinoma ◽  
Small Cell ◽  
Small Cell Lung ◽  
Cell Lung Carcinoma ◽  
Node Metastasis ◽  
Factor C

18008 Background: Angiogenesis is accepted as being essential for tumors to grow and metastasize to distant sites. Lymphatic metastasis is also an important means of tumor spread. Vascular endothelial growth factor C (VEGF-C) plays and important role in lymphangiogenesis and activates VEGFR (VEGF receptor)-3. Numerous studies suggest that tumor expression of VEGF-C is a significant prognostic factor in NSCLC. In non-small cell lung carcinoma (NSCLC), the relationship of lymphangiogenesis with lymph node metastasis and patient prognosis is unknown. Methods: A retrospective analysis of 78 patients who were diagnosed with NSCLC from 1987 to 2004 were analyzed for lymphatic vascular density (LVD). LVD was measured by use of D2–40 monoclonal antibody staining. Survival was assessed and Mantel-Cox and Wilcoxon signed rank tests were used for statistical analysis. Results: Intratumoral and peritumoral LVD was significantly higher than in the uninvolved adjacent lung, but showed no significant association with lymph node status at the time of tumor resection. Variables which appeared to affect survival in our study were the presence of lymph node metastasis (median survival 1,425 vs absence 467 days, p=0.002). The presence of VEGF staining inversely affected median survival (present 757 vs absent 1,944 days, p= 0.014). LVD ≤ 53 events per field 895 days vs >53 median survival 1,302 days, p+0.867. Survival appeared to not be affected by LVD. Conclusions: These data suggest that although lymphangiogenesis occurs in association with NSCLC, it may not be an important factor in lymph node metastasis or in survival. In fact, there is a suggestion that the number of lymphatics that a patient inherently has appears to be more important than lymphangiogenesis when it comes to the development of lymph node metastasis. No significant financial relationships to disclose.

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