Dataset Information

Spread Through Air Spaces (STAS) Is Prognostic in Atypical Carcinoid, Large Cell Neuroendocrine Carcinoma, and Small Cell Carcinoma of the Lung.

ABSTRACT:

Introduction

Tumor spread through air spaces (STAS) has prognostic significance in lung adenocarcinoma and squamous cell carcinoma. We sought to investigate the prognostic importance of STAS in lung neuroendocrine tumors (NETs).

Methods

All tumor slides from patients with resected pathologic stage I to III lung NETs (N = 487) (299 with typical carcinoid [TC], 38 with atypical carcinoid [AC], 93 with large cell neuroendocrine carcinoma [LCNEC], and 57 with SCLC) treated between 1992 and 2012 were evaluated for presence of STAS. Cumulative incidence of recurrence (CIR) and lung cancer-specific cumulative incidence of death (LC-CID) were analyzed by using a competing-risks approach.

Results

STAS was identified in 26% of NETs (16% of TCs, 37% of ACs, 43% of LCNECs, and 46% of SCLCs). STAS was associated with distant metastasis, as well as with higher CIR and LC-CID in the overall cohort and in the AC, LCNEC, and SCLC cohorts (owing to a small number of recurrences and deaths [<5], prognostic analysis was not performed in the TC cohort). In multivariable analysis stratified by stage, STAS was significantly associated with higher CIR (subhazard ratio = 2.85, 95% confidence interval: 1.73-4.68, p < 0.001) and LC-CID (subhazard ratio = 2.72, 95% confidence interval: 1.57-4.70, p < 0.001), independent of histologic subtype. STAS was independently associated with CIR and LC-CID in the LCNEC cohort and LC-CID in the SCLC cohort.

Conclusions

In patients with lung NETs, STAS is associated with early distant metastasis and worse LC-CID. In patients with LCNEC or SCLC, STAS is an independent poor prognostic factor.

SUBMITTER: Aly RG

PROVIDER: S-EPMC8160527 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background Spread through air spaces (STAS), as a new pattern of invasion, was officially proposed by the World Health Organization (WHO) in 2015, and its importance was reiterated in 2021. Since it was proposed, numerous studies have confirmed that STAS is associated with poor prognosis, but there are relatively few studies related to the prognosis of postoperative patients with lung squamous cell carcinoma. By synthesizing different predictive variables, nomogram can obtain the individual digital probability of clinical events succinctly and intuitively, which can meet our needs for personalized medicine. In this study, our goal is to explore the prognostic value of STAS in lung squamous cell carcinoma and establish a prognostic prediction model. Methods Under six inclusion criteria, 540 postoperative patients were enrolled in the study. STAS was re-evaluated by pathologists at Ningbo Clinicopathological Diagnosis Center. Progression-free survival (PFS) referred to the time from randomization to the first occurrence of disease progression or death of any cause. Recurrences were confirmed by clinical, radiological or pathological assessment. The survival information was collected by telephone and outpatient follow-up. A total of 540 patients were randomly divided into groups in a 6:4 ratio for survival analysis to determine the correlation between STAS and prognosis. Cox regression was used for univariate and multivariate analysis, so as to establish a predictive model. The assessment of the nomogram was carried out by receiver operating characteristic (ROC) curve analysis, calibration curve analysis and decision curve analysis (DCA). Results The overall 5-year survival rate was 70.35% in STAS-negative patients and 42.35% in STAS-positive patients. In all cohorts, STAS-negative patients had longer 5-year PFS than STAS-positive patients (P<0.001). Multivariate analysis showed that stage [stage II P=0.008, hazard ratio (HR) =1.792; stage III P<0.001, HR =3.148], tumor differentiation (well-differentiation P=0.021, HR =0.436), and STAS (P=0.026, HR =1.470) were independent predictors of PFS. The area under the curve (AUC) of model 5 in discovery cohort is 0.720, while the AUC of model 5 in validation cohort is 0.693. Conclusions The nomogram combined with STAS can provide a personalized visual survival probability prediction map for postoperative patients with lung squamous cell carcinoma, so as to aid in the pursuit of personalized medicine to a certain extent.

Project description:BackgroundSpread through air spaces (STAS) has recently been demonstrated to exhibit a negative impact on lung adenocarcinoma prognosis. However, most of these studies investigated STAS in nonmucinous adenocarcinoma. Here, we investigated the incidence of STAS in invasive mucinous adenocarcinoma (IMA) of the lung and evaluated whether tumor STAS was a risk factor of disease recurrence in IMA. We also examined clinicoradiologic factors in patients with IMA harboring STAS.MethodsWe reviewed pathologic specimens and imaging characteristics of primary tumors from 132 consecutive patients who underwent surgical resection for IMA to evaluate STAS. Patients with and without STAS were compared with respect to clinical characteristics as well as computed tomography (CT) imaging using logistic regression. The relationships between all variables including STAS and survival were analyzed.ResultsAmong a total of 132 patients, full pathologic specimens were available for 119 patients, and STAS was observed in 86 (72.3%). IMA patients with STAS were significantly associated with older age, presence of lobulated and spiculated margins on CT scan (P = 0.009, P = 0.006, and P = 0.027). In multivariate analysis for overall survival (OS), STAS was a borderline independent poor prognostic predictor (P = 0.028). Older age, history of smoking, higher T stage, presence of lymph node metastasis, and consolidative morphologic type remained independent predictors for OS.ConclusionsSTAS was associated with reduced OS and was a borderline independent poor prognostic factor in IMA. IMA with STAS was associated with older age and presence of lobulated and spiculated margins on CT scan.Key pointsSIGNIFICANT FINDINGS OF THE STUDY: Compared with other subtypes, IMA shows a higher incidence of STAS, which is an independent poor prognostic predictor even in IMA. Lobulated and spiculated margins on CT are associated with STAS.What this study addsConsidering that STAS can carry the potential for aerogenous metastasis, predicting STAS using preoperative surrogate CT imaging is desirable to avoid limited resection.

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