Diagnosing a pulmonary neuroendocrine neoplasm (NEN) may be difficult, challenging clinical decision making. In this review, the following key clinical and pathologic issues and informative molecular markers are being discussed: (1) What is the preferred outcome parameter for curatively resected low-grade NENs (carcinoid), for example, overall survival or recurrence-free interval? (2) Does the WHO classification combined with a Ki-67 proliferation index and molecular markers, such as OTP and CD44, offer improved prognostication in low-grade NENs? (3) What is the value of a typical versus atypical carcinoid diagnosis on a biopsy specimen in local and metastatic disease? Diagnosis is difficult in biopsy specimens and recent observations of an increased mitotic rate in metastatic carcinoid from typical to atypical and high-grade NEN can further complicate diagnosis. (4) What is the (ir)relevance of morphologically separating large cell neuroendocrine carcinoma (LCNEC) SCLC and the value of molecular markers (RB1 gene and pRb protein or transcription factors NEUROD1, ASCL1, POU2F3, or YAP1 [NAPY]) to predict systemic treatment outcome? (5) Are additional diagnostic criteria required to accurately separate LCNEC from NSCLC in biopsy specimens? Neuroendocrine morphology can be absent owing to limited sample size leading to missed LCNEC diagnoses. Evaluation of genomic studies on LCNEC and marker studies have identified that a combination of napsin A and neuroendocrine markers could be helpful. Hence, to improve clinical practice, we should consider to adjust our NEN classification incorporating prognostic and predictive markers applicable on biopsy specimens to inform a treatment outcome-driven classification.
Bone metastases are common in patients with non-small cell lung cancer (NSCLC), often causing pain and a decrease in quality of life (QoL). The effect of bone-targeted agents is evaluated by reduction in skeletal-related events in which neither pain nor QoL are included. Radioisotopes can be administered for more diffuse bone pain that is not eligible for palliative radiotherapy. The evidence that bone-targeted agents relieve pain or improve QoL is not solid. We performed a systematic review of the effect of bone-targeted agents on pain and QoL in patients with NSCLC. Our systematic literature search included original articles or abstracts reporting on bisphosphonates, denosumab, or radioisotopes or combinations thereof in patients with bone metastases (≥5 patients with NSCLC), with pain, QoL, or both serving as the primary or secondary end point. Of the twenty-five eligible studies, 13 examined bisphosphonates (one also examined denosumab) and 12 dealt with radioisotopes. None of the randomized studies on bisphosphonates or denosumab evaluated pain and QoL as the primary end point. In the single-arm studies of bisphosphonates a decrease in pain or analgesic consumption was found for 38% to 77% of patients. QoL was included in five of 13 studies, but improvement was found in only two. No high-level evidence that bisphosphonates or denosumab reduce pain or improve QoL was found. Although the data are limited, radioisotopes seem to reduce pain with a rapid onset of action and duration of response of 1 to 3 months. The evidence that bisphosphonates or denosumab reduce or prevent pain in patients with NSCLC and bone metastases or that they have an influence on QoL is very weak. Radioisotopes can be used to reduce diffuse pain, although there is no high-level evidence supporting such use.
Conclusions:Our results showed the prognostic role of PD-L1, TGF-b and CD8 þ TILs in patients with advanced TETs, and their potential for development of anti-PD-1/PD-L1 therapies. Legal entity responsible for the study: Jie Wang. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.1813P Prevalence and prognostic value of PD-L1 expression in molecular subtypes of metastatic large cell neuroendocrine carcinoma (LCNEC)Background: Spread through air spaces (STAS) is a recently-recognized invasive pattern of lung cancer defined as 'micropapillary clusters, solid nests or single cells beyond the edge of the tumor into air spaces.' Since STAS has been shown to be a significant prognosticator for the postoperative survival, predicting STAS preoperatively by computed tomography (CT) might help determine the optimum surgical procedures. Methods: Information on STAS and preoperative CT were availablen 327 patients with resected lung adenocarcinomas. STAS was defined as tumor cells within air spaces in the lung parenchyma beyond the edge of the main tumor. The association of STAS with CT characteristics, such as vascular convergence, ground glass opacity (GGO), air bronchogram, notch, pleural indentation, spiculation, and cavitation, was analyzed. Results: Among the 327 patients with resected adenocarcinoma, 191 (58.4%) were positive for STAS. A univariable analysis demonstrated that STAS-positive adenocarcinomas were significantly associated with a larger radiological tumor diameter (P ¼ 0.02), the presence of vascular convergence (P < 0.01), notch (P < 0.01), pleural indentation (P ¼ 0.03), spiculation (P < 0.01), and the absence of GGO (P < 0.01) compared with STAS-negative ones. In a multivariable analysis, the presence of notch (P ¼ 0.01) and the absence of GGO (P < 0.01) were shown to be significantly associated with the STAS phenomenon. The odds ratio for STAS of notch-positive and GGO-negative adenocarcinomas against notch-negative and GGO-positive ones was 5.01 (P < 0.01). Conclusions:The presence of notch and the absence of GGO were independently associated with the STAS phenomenon. These results will prove helpful in identifying STAS-positive adenocarcinoma by CT prior to surgical resection.Legal entity responsible for the study: Gouji Toyokawa. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
IntroductionStage 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.MethodsEleven 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).ResultsAll 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.ConclusionStage 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.
Introduction Neuroendocrine neoplasms (NEN) can originate in different organs, e.g. the gastroenteral tract (GE), pancreas (Pan) or lung (L). Our aim was to examine metastatic patterns for patients with NEN of various primary origins with a special focus on brain metastases to indicate utility for screening. Methods All NEN patients except for small cell lung cancer registered in the Netherlands Cancer Registry from 2008-2018 were selected. Metastatic patterns at initial diagnosis for NEN with different primary origin were compared. In a subcohort of patients from two referral hospitals (2014-2019), additional information on for example development of metastases after initial presentation was available. Results In the nationwide cohort 4,768/11,120 (43%) patients had metastatic disease at diagnosis (GE 1,504/4,710 (32%), Pan 489/1,150 (43%), L 1,230/2,978 (41%)). For GE- and Pan-NEN, the most prevalent metastatic site was the liver (25% and 39%), followed by distant lymph nodes (8% and 8%), whereas only few patients with brain metastases were identified (0% in both). In contrast, for L-NEN, prevalence of metastases in liver (19%), brain (9%), lung (7%) and bone (14%) was more equal. In the reference network cohort, slightly more NEN patients had metastatic disease (260/539, 48%) and similar metastatic patterns were observed. Conclusion Almost half of NEN patients were diagnosed with synchronous metastatic disease. L-NEN have a unique metastatic pattern compared to GE- and Pan-NEN. Remarkably, an important part of L-NEN metastases were in the brain, whereas brain metastases were almost absent in GE- and Pan-NEN, indicating utility of screening in L-NEN.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.