&lt;p&gt;Immune Checkpoint Inhibitor Therapy Achieved Complete Response for Drug-Sensitive&lt;em&gt; EGFR/ALK&lt;/em&gt; Mutation-Negative Metastatic Pulmonary Large-Cell Neuroendocrine Carcinoma with High Tumor Mutation Burden: A Case Report&lt;/p&gt;

Zhang, Xin; Sun, Y. K.; Miao, Yuan; Xu, Shun

doi:10.2147/ott.s259893

Cited by 13 publications

(9 citation statements)

References 25 publications

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“…Indeed, on the basis of the studies discussed, genomic subtyping represents a valid tool to predict prognosis and detect the best treatment for each LCNEC patient (43). With regard to potential future opportunities, some cases are reported of patients treated with checkpoint inhibitors, often achieving radiological and clinical response, in particular after platinum-based first-line treatment failure (107)(108)(109)(110)(111). A few data are also available concerning targeted therapy, due to a low frequency of driver mutations in LCNEC patients, but mostly of them have reported a moderate efficacy of TKIs in this subset of disease (114,115,119,120).…”

Section: Discussionmentioning

confidence: 99%

Large Cell Neuro-Endocrine Carcinoma of the Lung: Current Treatment Options and Potential Future Opportunities

et al. 2021

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Large-cell neuroendocrine carcinomas of the lung (LCNECs) are rare tumors representing 1–3% of all primary lung cancers. Patients with LCNEC are predominantly male, older, and heavy smokers. Histologically, these tumors are characterized by large cells with abundant cytoplasm, high mitotic rate, and neuroendocrine immunohistochemistry-detected markers (chromogranin-A, synaptophysin, and CD56). In 2015 the World Health Organization classified LCNEC as a distinct subtype of pulmonary large-cell carcinoma and, therefore, as a subtype of non-small cell lung carcinoma (NSCLC). Because of the small-sized tissue samples and the likeness to other neuroendocrine tumors, the histological diagnosis of LCNEC remains difficult. Clinically, the prognosis of metastatic LCNECs is poor, with high rates of recurrence after surgery alone and overall survival of approximately 35% at 5 years, even for patients with early stage disease that is dramatically shorter compared with other NSCLC subtypes. First-line treatment options have been largely discussed but with limited data based on phase II studies with small sample sizes, and there are no second-line well defined treatments. To date, no standard treatment regimen has been developed, and how to treat LCNEC is still on debate. In the immunotherapy and targeted therapy era, in which NSCLC treatment strategies have been radically reshaped, a few data are available regarding these opportunities in LCNEC. Due to lack of knowledge in this field, many efforts have been done for a deeper understanding of the biological and molecular characteristics of LCNEC. Next generation sequencing analyses have identified subtypes of LCNEC that may be relevant for prognosis and response to therapy, but further studies are needed to better define the clinical impact of these results. Moreover, scarce data exist about PD-L1 expression in LCNEC and its predictive value in this histotype with regard to immunotherapy efficacy. In the literature some cases are reported concerning LCNEC metastatic patients carrying driver mutations, especially EGFR alterations, showing targeted therapy efficacy in this setting of disease. Due to the rarity and the challenging understanding of LCNEC, in this review we aim to summarize the management options currently available for treatment of LCNEC.

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Section: Discussionmentioning

confidence: 99%

Large Cell Neuro-Endocrine Carcinoma of the Lung: Current Treatment Options and Potential Future Opportunities

et al. 2021

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“…To the best of our knowledge, the CR of pulmonary LCNEC to immune checkpoint inhibitors (ICI) is extremely rare, with only three case reports in the literature. [5][6][7] LCNEC is classified as pulmonary neuroendocrine carcinoma by the 2015 World Health Organization classification. The prognosis of pulmonary LCNEC is poor and standard therapy has not yet been established.…”

Section: Discussionmentioning

confidence: 99%

Complete and durable response of pulmonary large‐cell neuroendocrine carcinoma to pembrolizumab

et al. 2021

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Background Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive tumor with a poor prognosis and standard therapy has not yet been established. Case A 65‐year‐old male with a cough for 2 months presented to our hospital. He was clinically diagnosed with non small cell lung cancer cT3N1M0 stage IIIA and underwent right pneumonectomy. The final diagnosis was pulmonary LCNEC pT3N1M0 stage IIIA. Multiple subcutaneous masses were detected 4 months after surgery, and biopsy revealed postoperative recurrence and metastasis. Chemotherapy with carboplatin plus etoposide was initiated. Subcutaneous masses increased and multiple new brain metastases developed after two cycles. Additional tests revealed that epidermal growth factor receptor and anaplastic lymphoma kinase were negative, and the programmed death ligand 1 (PD‐L1) expression rate in tumor cells was 40% (22C3 clones). The primary cells infiltrating the tumor were CD3‐positive T cells and CD138‐positive plasma cells. Second‐line treatment with pembrolizumab was started. The shrinkage of subcutaneous masses was observed after one cycle, and the tumor had completely disappeared after six cycles. Treatment was continued for approximately 2 years. This response has been maintained for 4 years and is still ongoing. Conclusion Pembrolizumab may be used as a treatment option for pulmonary LCNEC.

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“…For example, recent studies showed that lung LCNEC has a quite specific pattern of programmed cell-death-protein-1-ligand-1 (PD-L1) expression, which is associated with prognosis. 21,22) Thus, immunotherapy may be a new strategy to manage LCNEC in the near future, although only a case report 23) and a small cohort NMC Case Report Journal Vol. 8, 2021 AWD: alive with disease, C: chemotherapy, DWD: dead with disease, LCNEC: large cell neuroendocrine carcinoma, ND: not described, NED: no evidence of disease (alive), R: radiation therapy, S: surgery.…”

Section: Discussionmentioning

confidence: 99%

“…For example, recent studies showed that lung LCNEC has a quite specific pattern of programmed cell-death-protein-1-ligand-1 (PD-L1) expression, which is associated with prognosis. 21 , 22) Thus, immunotherapy may be a new strategy to manage LCNEC in the near future, although only a case report 23) and a small cohort study 24) have been reported in lung. We need more studies from various standpoints to address sinonasal LCNEC.…”

Section: Discussionmentioning

confidence: 99%

Large Cell Neuroendocrine Carcinoma in the Sinonasal Cavity with Large Intracranial Extension Treated with Endonasal Endoscopic and Transcranial Combined Surgery: A Case Report

Rai

Nishioka

Hara

2021

NMC Case Report Journal

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Large cell neuroendocrine carcinoma (LCNEC) is a rare malignant tumor that typically arises in the lungs. It is especially rare in the sinonasal cavity, and treatment has not been established. In this study, we present the case of a 56-year-old woman with a large sinonasal LCNEC that extended into her brain. We performed endonasal endoscopic and transcranial combined surgery followed by chemoradiation therapy. The combined surgery enabled us to approach and remove the extensive tumor from two different directions at one time less invasively. We have achieved good tumor control for 18 months so far.

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<p>Immune Checkpoint Inhibitor Therapy Achieved Complete Response for Drug-Sensitive<em> EGFR/ALK</em> Mutation-Negative Metastatic Pulmonary Large-Cell Neuroendocrine Carcinoma with High Tumor Mutation Burden: A Case Report</p>

Cited by 13 publications

References 25 publications

Large Cell Neuro-Endocrine Carcinoma of the Lung: Current Treatment Options and Potential Future Opportunities

Large Cell Neuro-Endocrine Carcinoma of the Lung: Current Treatment Options and Potential Future Opportunities

Complete and durable response of pulmonary large‐cell neuroendocrine carcinoma to pembrolizumab

Large Cell Neuroendocrine Carcinoma in the Sinonasal Cavity with Large Intracranial Extension Treated with Endonasal Endoscopic and Transcranial Combined Surgery: A Case Report

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