Defining the role of adjuvant therapy for early-stage large cell neuroendocrine carcinoma

Abstract Background Large cell neuroendocrine carcinoma is a very rare ovarian neoplasm that has a poor clinical outcome even in the early stage, and there is as yet no established treatment. Diagnostic laparoscopy has been used to determine the possibility of primary optimal cytoreductive surgery or neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer. However, the role of diagnostic laparoscopy is still unclear in large cell neuroendocrine carcinoma due to its rarity. Case presentation A 31-year-old woman with abdominal distention was referred to our hospital. She was strongly suspected of having advanced ovarian cancer because of a huge pelvic mass, massive ascites, and their appearance on medical imaging. However, cytological examinations from ascitic fluid by abdominal paracentesis did not show any malignant cells. She underwent diagnostic laparoscopy to evaluate the possibility of primary optimal cytoreductive surgery, and only tissue sampling was performed for pathological diagnosis because of the countless disseminated lesions of various sizes in the intraperitoneal organs. The patient had no postoperative complications, leading to the early start of postoperative chemotherapy. Conclusions To date, there have been no systematic reviews that focused on determining the treatment strategy using laparoscopy. Diagnostic laparoscopy can be helpful to determine the optimal treatment, including primary debulking surgery, neoadjuvant chemotherapy, or best supportive care, assisting in decision-making particularly for patients with advanced large cell neuroendocrine carcinoma with carcinomatous peritonitis.

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91P The role of endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) in the diagnosis of large cell neuroendocrine carcinoma (LCNEC)

Journal of Thoracic Oncology ◽

10.1016/s1556-0864(21)01933-x ◽

2021 ◽

Vol 16 (4) ◽

pp. S744-S745

Author(s):

B. Teng ◽

M. Rice ◽

D. Rana ◽

D. Shelton ◽

N. Narine ◽

...

Keyword(s):

Neuroendocrine Carcinoma ◽

Large Cell ◽

Needle Aspiration ◽

Large Cell Neuroendocrine Carcinoma ◽

Endobronchial Ultrasound ◽

Ultrasound Guided ◽

Transbronchial Needle Aspiration

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MA23.07 Defining the Role of Adjuvant Therapy for Early Stage Large Cell Neuroendocrine Lung Cancer

Journal of Thoracic Oncology ◽

10.1016/j.jtho.2018.08.516 ◽

2018 ◽

Vol 13 (10) ◽

pp. S440

Author(s):

E. Wakeam ◽

S. Stokes ◽

A. Adibfar ◽

N. Leighl ◽

M. Giuliani ◽

...

Keyword(s):

Lung Cancer ◽

Adjuvant Therapy ◽

Early Stage ◽

Large Cell

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

European Respiratory Journal ◽

10.1183/13993003.00618-2015 ◽

2015 ◽

Vol 47 (2) ◽

pp. 615-624 ◽

Cited By ~ 39

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.

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Pure Large Cell Neuroendocrine Carcinoma of Ovary: A Rare Clinical Entity and Review of Literature

Case Reports in Oncological Medicine ◽

10.1155/2012/120727 ◽

2012 ◽

Vol 2012 ◽

pp. 1-4 ◽

Cited By ~ 3

Author(s):

P. N. Shakuntala ◽

K. Uma Devi ◽

K. Shobha ◽

U. D. Bafna ◽

M. Geetashree

Keyword(s):

Neuroendocrine Carcinoma ◽

Neuroendocrine Tumour ◽

Early Stage ◽

Intraepithelial Neoplasia ◽

Large Cell ◽

Large Cell Neuroendocrine Carcinoma ◽

World Health ◽

Type I ◽

Cervical Intraepithelial Neoplasia Grade ◽

Large Tumor

Large cell neuroendocrine carcinoma (LCNEC) of the ovary is a rare tumor and is now included in the World Health Organization tumor classification. Its prognosis is generally very poor even when the diagnosis is made at an early stage. We report a case of pure large cell neuroendocrine tumour of ovary, appearing 9 months following laparoscopic type I hysterectomy, bilateral pelvic lymph node dissection with ovarian preservation of anatomically normal looking ovaries performed for a cervical biopsy diagnosis of cervical intraepithelial neoplasia grade III with foci of invasion. The rarity lies in the rapid onset (9 months) of a large tumor following conservation of an anatomically normal ovaries. Surgical debulking and five cycles of chemotherapy (Etoposide and Cisplatin) were administered to the woman. She is on followup with no clinical or radiological evidence of disease recurrence for 6 months.

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Long lasting octreotide LAR therapy in large cell neuroendocrine carcinoma (LCNEC) of the lung

Clinical Management Issues ◽

10.7175/cmi.v4i1s.1066 ◽

2015 ◽

Vol 4 (1S) ◽

pp. 15-18

Author(s):

Alfredo Butera

Keyword(s):

Neuroendocrine Carcinoma ◽

Poor Prognosis ◽

Large Cell ◽

Mechanisms Of Action ◽

Large Cell Neuroendocrine Carcinoma ◽

Optimal Dosage ◽

Biological Behaviour ◽

Octreotide Lar ◽

Individual Tumour

In this article we report a case of a patient with large cell neuroendocrine carcinoma (LCNEC) of the lung. Patients with LCNEC usually have poor prognosis and the benefit of adjuvant chemotherapy for these patients has not been fully established. This case suggests that octreotide LAR, a somatostatine analogue (SSA), can be useful in the treatment of neuroendocrine carcinoma also as maintenance therapy in association with chemotherapy. Further studies, regarding individual tumour biological behaviour and SSAs optimal dosage, could be useful to optimise treatment and to add new insights into the mechanisms of action and the role of SSAs in the therapy of NETs.

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Evaluation of the efficacy of cisplatin–etoposide and the role of thoracic radiotherapy and prophylactic cranial irradiation in large cell neuroendocrine carcinoma

European Journal of Cancer ◽

10.1016/s0959-8049(17)30659-7 ◽

2017 ◽

Vol 72 ◽

pp. S180-S181

Author(s):

A. Prelaj ◽

S.E. Rebuzzi ◽

G. Del Bene ◽

J.R. Giròn Berrìos ◽

A. Emiliani ◽

...

Keyword(s):

Neuroendocrine Carcinoma ◽

Large Cell ◽

Cranial Irradiation ◽

Prophylactic Cranial Irradiation ◽

Large Cell Neuroendocrine Carcinoma ◽

Thoracic Radiotherapy

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Survival After Lobectomy Versus Sublobar Resection for Stage IA Large-Cell Neuroendocrine Carcinoma of the Lung: A Population-Based Study

10.21203/rs.3.rs-386977/v1 ◽

2021 ◽

Author(s):

xiangyang yu ◽

Zirui Huang ◽

Mengqi Zhang ◽

Yongbin Lin ◽

Rusi Zhang ◽

...

Keyword(s):

Multivariate Analysis ◽

Lymph Nodes ◽

Neuroendocrine Carcinoma ◽

Early Stage ◽

Large Cell ◽

Large Cell Neuroendocrine Carcinoma ◽

Sublobar Resection ◽

Oncological Outcomes ◽

Stage Ia ◽

Lymph Nodes Dissection

Abstract Background: Due to the low incidence of pulmonary large cell neuroendocrine carcinoma (LCNEC), the survival analysis for comparing lobectomy and sublobar resection (SLR) for stage IA LCNEC remains scarce. Methods: Patients diagnosed with pathological stage IA LCNEC between 1998 and 2016 were extracted from the Survenillance, Epidemiology, and End Results (SEER) database. The oncological outcomes were cancer-specific survival (CSS) and overall survival (OS). Kaplan-Meier analysis and Cox multivariate analysis were used to identify the independent prognostic factors for OS and CSS. Furthermore, propensity score matching (PSM) was performed between SLR and lobectomy to adjust the confounding factors. Results: A total of 308 patients with stage IA LCNEC met the inclusion criteria: 229 patients (74.4%) received lobectomy and 79 patients (25.6%) received SLR. Patients who underwent SLR were older (P<0.001), had smaller tumor size (P=0.010) and fewer lymph nodes dissection (P<0.001). The 5-year CSS and OS rates were 56.5% and 42.9% for SLR, and 67.8% and 55.7% for lobectomy, respectively (P=0.037 and 0.019, respectively). However, multivariate analysis did not identify any differences between SLR group and lobectomy group in CSS (P=0.135) and OS (P=0.285); and the PSM also supported these results. In addition, age at diagnosis and laterality of tumor were identified as significant predictors for CSS and OS, whereas the number of lymph nodes dissection was a significant predictor for CSS. Conclusions: Although SLR is not inferior to lobectomy in terms of oncological outcomes for patients with stage IA LCNEC, more lymph nodes can be dissected or sampled during lobectomy. Lobectomy should be considered as a standard procedure for patients with early-stage LCNEC who are able to withstand lobectomy.

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Role of Chemotherapy and the Receptor Tyrosine Kinases KIT, PDGFRα, PDGFRβ, and Met in Large-Cell Neuroendocrine Carcinoma of the Lung

Journal of Clinical Oncology ◽

10.1200/jco.2005.02.8233 ◽

2005 ◽

Vol 23 (34) ◽

pp. 8774-8785 ◽

Cited By ~ 183

Author(s):

Giulio Rossi ◽

Alberto Cavazza ◽

Alessandro Marchioni ◽

Lucia Longo ◽

Mario Migaldi ◽

...

Keyword(s):

Survival Rate ◽

Neuroendocrine Carcinoma ◽

Tyrosine Kinases ◽

Receptor Tyrosine Kinases ◽

Large Cell ◽

Large Cell Neuroendocrine Carcinoma ◽

Stage I ◽

Cell Lung Carcinoma ◽

Mutational Status

PurposePulmonary large-cell neuroendocrine carcinoma (LCNEC) is a relatively uncommon, high-grade neuroendocrine tumor sharing several features with small-cell lung carcinoma (SCLC) but currently considered as a variant of non-SCLC and accordingly treated with poor results. Little is known about the optimal therapy of LCNEC and the possible therapeutic molecular targets.Patients and MethodsWe reviewed 83 patients with pure pulmonary LCNEC to investigate their clinicopathologic features, therapeutic strategy, and immunohistochemical expression and the mutational status of the receptor tyrosine kinases (RTKs) KIT, PDGFRα, PDGFRβ, and Met.ResultsLCNEC histology predicted a dismal outcome (overall median survival, 17 months) even in stage I patients (5-year survival rate, 33%). LCNEC strongly expressed RTKs (KIT in 62.7% of patients, PDGFRα in 60.2%, PDGFRβ in 81.9%, and Met in 47%), but no mutations were detected in the exons encoding for the relevant juxtamembrane domains. Tumor stage and size (≥ 3 cm) and Met expression were significantly correlated with survival. At univariate and multivariate analysis, SCLC-based chemotherapy (platinum-etoposide) was the most important variable correlating with survival, both in the adjuvant and metastatic settings (P < .0001).ConclusionPulmonary LCNEC represents an aggressive tumor requiring multimodal treatment even for resectable stage I disease, and LCNEC seems to respond to adjuvant platinum-etoposide–based chemotherapy. Patients who received this therapy had the best survival rate. Despite our failure in finding mutational events in the tested RTKs, the strong expression of KIT, PDGFRα, PDGFRβ, and Met in tumor cells suggests an important role of these RTKs in LCNEC, and these RTKs seem to be attractive therapeutic targets.

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