Prognostic significance of laterality in lung neuroendocrine tumors

Abstract

Purpose: Well-differentiated lung neuroendocrine tumors (Lu-NET) are classified as typical (TC) and atypical (AC) carcinoids, based on mitotic counts and necrosis. However, prognostic factors, other than tumor node metastasis (TNM) stage and the histopathological diagnosis, are still lacking. The current study is aimed to identify potential prognostic factors to better stratify lung NET, thus, improving patients’ treatment strategy and follow-up. Methods: A multicentric retrospective study, including 300 Lung NET, all surgically removed, from Italian and Spanish Institutions. Results: Median age 61 years (13–86), 37.7% were males, 25.0% were AC, 42.0% were located in the lung left parenchyma, 80.3% presented a TNM stage I-II. Mitotic count was ≥2 per 10 high-power field (HPF) in 24.7%, necrosis in 13.0%. Median overall survival (OS) was 46.1 months (0.6–323), median progression-free survival (PFS) was 36.0 months (0.3–323). Female sex correlated with a more indolent disease (T1; N0; lower Ki67; lower mitotic count and the absence of necrosis). Left-sided primary tumors were associated with higher mitotic count and necrosis. At Cox-multivariate regression model, age, left-sided tumors, nodal (N) positive status and the diagnosis of AC resulted independent negative prognostic factors for PFS and OS. Conclusions: This study highlights that laterality is an independent prognostic factors in Lu-NETs, with left tumors being less frequent but showing a worse prognosis than right ones. A wider spectrum of clinical and pathological prognostic factors, including TNM stage, age and laterality is suggested. These parameters could help clinicians to personalize the management of Lu-NET.

Thyroid transcription factor‐1 expression in lung neuroendocrine tumours: a gender-related biomarker?

“…In this analysis the 3-year survival rates resulted 84.6% and 87.7% and the 5-years survival rates of 80% vs. 84% for male and female, respectively. For lung NET a sex-difference has been described, with, even in this case, more favourable trends in female in a previous work by our group [ 13 ]. According to the Cox-univariate regression model a significant impact on patients’ outcome for sex was demonstrated, with male sex associated with dismal PFS ( p < 0.0001) and OS ( p < 0.0001).…”

“…This issue is of note, in the setting of lung NET, given that established prognostic factors, beyond the histological subtype of TC (associated to a better prognosis) vs. AC and the pathological TNM stage, are missing. In this context, in a previous work by our group we postulated a role for primary lung NET laterality [ 13 ]. In that retrospective multicentre analysis, tumours located in the left lung clearly presented a higher biological aggressiveness (expressed as higher proliferation index, as mitotic count and Ki-67, more common presence of necrosis and higher tumour grade).…”

Treatment outcome and prognostic analysis of advanced large cell neuroendocrine carcinoma of the lung

“…For the prognosis of patients with LCNEC, previous studies have shown that laterality is an independent prognostic factor in LCNEC, with fewer tumors on the left side but a worse prognosis than on the right 14 . Also in neuroendocrine tumors, angiogenic factor expression is increased, suggesting a possible prognostic marker 15 .…”

Platin‑based chemotherapy does not improve survival in patients with non‑metastatic resected typical carcinoid tumors

“…Recent studies have reported that older age, left side and high ki-67 index were poor prognostic factors (29)(30)(31). In addition, female patients are expected to have improved outcomes due to the protective effect of progesterone and estrogen via regulating immune cell response and suppressing tumor growth in mainly low-grade neuroendocrine neoplasms (32,33).…”