Dear Colleagues, 

Thoracic Neuroendocrine Tumors (NETs) are classified into well-differentiated (low-grade typical carcinoids [TCs] and intermediate-grade atypical carcinoids [ACs]) and poorly differentiated (high-grade large cell neuroendocrine carcinoma LCNEC) or small cell lung carcinoma (SCLC) neuroendocrine carcinoma. Despite the increasing incidence of thoracic NETS, awareness [1] and the development of personalized approach therapies in these patients lag.

Well-differentiated carcinoids, as atypical carcinoid tumors in the lung, can recur and become challenging. Unfortunately, the guidelines regarding adjuvant therapies remain unclear, and current regimens' survival benefit is questionable [2]. There is a critical need to update the classification, diagnosis, and treatment of lung NETs. The development of molecular markers to provide evidence supporting the treatment of this underserved type of NET is an area of unmet need.

Effective systemic therapies for patients with advanced, progressive neuroendocrine lung tumors are very rare. However, recently, everolimus was associated with significant improvement in progression-free survival in patients with progressive lung neuroendocrine tumors [3]. Further drug development is needed.

To date, there is only one biomarker-based clinical trial, S1929, in the poorly differentiated NETs; SCLC that has recently completed enrollment for screening, that attempts to stratify patients with SCLC to receive PARP inhibitor based on SLFN11 that is expressed by more than half of patients with SCLC. Further knowledge of predictive factors and novel therapies is needed.

References:

1. Neuroendocrine Tumors of the Lung: Current Challenges and Advances in the Diagnosis and Management of Well-Differentiated Disease. Hendifar, Marchevsky, and Tuli. Journal of Thoracic Oncology Vol. 12 No. 3: 425–436.
2. Survival Benefit of Adjuvant Chemotherapy in Pulmonary Carcinoid: A systematic Review. Philip Sobash and Nagla Abdel Karim. NCCN Virtual Annual Conference 2021 General Poster Session.
3. Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Yao, Fazio, Singh et. al. The Lancet. Volume 387, Issue 10022, 5–11 March 2016, Pages 968–977.

Dr. Nagla Abdel Karim
Dr. Asad Ullah
Dr. Jaffar Khan
Prof. Dr. Fernando Mendes
Guest Editors

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• thoracic neuroendocrine tumors
• lung NETs
• low-grade typical carcinoids
• TCs
• intermediate-grade atypical carcinoids
• ACs
• high-grade large cell neuroendocrine carcinoma LCNEC
• small cell lung carcinoma (SCLC) neuroendocrine carcinoma

Title: Demographics and clinicopathologic profile of pulmonary sarcomatoid carcinoma with survival analysis and an introduction to genomic landscape
Authors: Asad Ullah1 , Asim Ahmed2 , Abdul Qahar Khan Yasinzai3 , Kue Tylor Lee2 , Israr Khan4 , Bina Asif5 , Bisma Tareen3 , Saleh Heneidi6 , Jaffar Khan 7 , Hina Khan8 , Nabin R. Karki9 , Jaydira Del River
Affiliation: 1 Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville TN 37232, USA, drasadkhankakar@gmail.com 2 Medical College of Georgia, Augusta, GA, 30912, gkenol@agusta.edu, kulee@augusta.edu 3 Department of Medicine, Bolan Medical College, Quetta 83700, Pakistan, abdul.qahar.apk@gmail.com 4 Hackensack Medical Center, NJ 5 Bannu Medical College, Bannu 28100, Pakistan doctorbina2017@gmail.com 6 Department of Pathology, Cedars Sinai Medical Center, Los Angeles, CA 90048, USA, saleh.heneidi@cshs.org 7 Department of Pathology, Indiana University School of Medicine, Indianapolis, IN 46202, USA, khanja@iu.edu 8 Division of Hematology and Oncology, Warren Alpert Medical School of Brown University, Providence, RI. 9Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36604, USA nkarki@health.southalabama.edu 10 National Institute of Health (NIH) Bethesda, MD 11 Inova Schar Cancer Institute, University of Virginia, Fairfax, VA
Abstract: Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC) with aggressive clinical nature and poor prognosis. New ways to effectively diagnose and treat PSC are evolving, with a promise of novel targeted therapeutics. In this study, we analyze demographics, tumor characteristics, treatment modalities, and outcomes of PSC. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database was reviewed to analyze cases of pulmonary sarcomatoid carcinoma from 2000 to 2018. Results: A total of 5,259 patients with PSC were identified. Most patients were between 70-79 years of age (32.2%), males (59.1%) and Caucasians (83.7%). The male-to-female ratio was 1.45:1. Most tumors were between 1-7 cm in size (69.4%) and poorly differentiated (grade III) (72.9%). The overall 5-year survival was 15.6% (95% confidence interval (95% CI) = 14.4-16.9)), and the cause-specific 5-year survival was 19.7% (95% CI = 18.3-21.1). The five-year survival for those treated with each modality were as follows: chemotherapy, 19.9% (95% CI = 17.7-22.2); surgery, 41.7% (95% CI = 38.9-44.6); radiation, 19.1% (95% CI=15.1-23.5); and combination therapy, 24.8% (95% CI=17.6-32.7) respectively. On multivariable analysis, age, male gender, distant stage, tumor size, bone metastasis, brain metastasis, and liver metastasis were associated with increased mortality, and chemotherapy and surgery were associated with reduced mortality (p<0.001). Best survival outcomes were achieved with combination of surgery and chemotherapy or surgery only. Conclusion: PSC is a rare and aggressive subtype of NSCLC, usually affecting Caucasian males between 70-79 years of age. Male gender, older age, and distant spread were associated with poor clinical outcomes; treatment with chemotherapy and surgery were associated with better survival outcomes.