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Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer-Specific Death in Squamous Cell Carcinoma.

ABSTRACT: Spread through air spaces (STAS) is a recently recognized pattern of invasion in lung adenocarcinoma; however, it has not yet been characterized in squamous cell carcinoma (SCC).We reviewed 445 resected stage I to III lung SCCs and investigated the clinical significance of STAS. Cumulative incidence of recurrence and lung cancer-specific death were evaluated by competing risks analyses and overall survival by Cox models.Of the total 445 patients, 336 (76%) were older than 65 years. Among the 273 patients who died, 91 (33%) died of lung cancer whereas the remaining ones died of competing events or unknown cause. STAS was observed in 132 patients (30%) and the frequency increased with stage. The cumulative incidences of any, distant, and locoregional recurrence as well as lung cancer-specific death were significantly higher in patients with STAS compared with in those without STAS, whereas there was no statistically significant difference in overall survival. In multivariable models for any recurrence and lung cancer-specific death, STAS was an independent predictor for both outcomes (p = 0.034 and 0.016, respectively).STAS was present in one-third of resected lung SCCs. In competing risks analysis in a cohort in which three-fourths of the patients were elderly, STAS was associated with lung cancer-specific outcomes. Our findings suggest that STAS is one of the most prognostically significant histologic findings in lung SCC.

SUBMITTER: Lu S

PROVIDER: S-EPMC5639476 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer-Specific Death in Squamous Cell Carcinoma.

Lu Shaohua S Tan Kay See KS Kadota Kyuichi K Eguchi Takashi T Bains Sarina S Rekhtman Natasha N Adusumilli Prasad S PS Travis William D WD

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 20160928 2

<h4>Introduction</h4>Spread through air spaces (STAS) is a recently recognized pattern of invasion in lung adenocarcinoma; however, it has not yet been characterized in squamous cell carcinoma (SCC).<h4>Methods</h4>We reviewed 445 resected stage I to III lung SCCs and investigated the clinical significance of STAS. Cumulative incidence of recurrence and lung cancer-specific death were evaluated by competing risks analyses and overall survival by Cox models.<h4>Results</h4>Of the total 445 patien ...[more]

PMID: 27693541

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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.

Project description:IntroductionSpread through air spaces (STAS) is a form of invasion wherein tumor cells extend beyond the tumor edge within the lung parenchyma. In lung adenocarcinoma (ADC), we investigated the (1) association between STAS and procedure-specific outcomes (sublobar resection and lobectomy), (2) effect of surgical margin-to-tumor diameter ratio in STAS-positive patients, and (3) potential utility of frozen sections (FSs) for detecting STAS intraoperatively.MethodsWe investigated 1497 patients who underwent lobectomy (n = 970) or sublobar resection (n = 527) for T1N0M0 lung ADC after propensity score matching. Outcomes were analyzed by using a competing risks approach. The effect of margin-to-tumor ratio on recurrence pattern (locoregional and distant) was investigated in patients who underwent sublobar resection. Five pathologists evaluated the feasibility of intraoperatively identifying STAS by using FSs (sensitivity, specificity, and interrater reliability).ResultsOn multivariable analysis after propensity score matching (349 pairs/procedure), sublobar resection was significantly associated with recurrence (subhazard ratio = 2.84 [p < 0.001]) and lung cancer-specific death (subhazard ratio = 2.63 [p = 0.021]) in patients with STAS but not in those without STAS. Patients with STAS who underwent sublobar resection had a higher risk of locoregional recurrence regardless of margin-to-tumor ratio (for a margin-to-tumor ratio of ≥1 versus <1, the 5-year cumulative incidence of recurrence rates were 16% and 25%, respectively); among patients without STAS, locoregional recurrences occurred in patients with margin-to-tumor ratio lower than 1 (a 5-year cumulative incidence of recurrence rate of 7%). The sensitivity and specificity for detecting STAS by use of FSs were 71% and 92%, with substantial interrater reliability (Gwet's AC1, 0.67).ConclusionsIn patients with T1 lung ADC with STAS, lobectomy was associated with better outcomes than sublobar resection was. Pathologists can recognize STAS on FSs.

Dataset Information

Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer-Specific Death in Squamous Cell Carcinoma.

Publications

Spread through Air Spaces (STAS) Is an Independent Predictor of Recurrence and Lung Cancer-Specific Death in Squamous Cell Carcinoma.

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