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OBJECTIVE: To explore the predictive value of preoperative prognostic nutritional index (PNI) and systemic immune inflammation index (SII) in relation to the efficacy and prognosis in patients with non-small cell lung cancer (NSCLC) undergoing neoadjuvant chemotherapy (NACT). METHODS: Data of patients with stage IIIA-N2 NSCLC who received NACT in the 910th Hospital of Chinese People's Liberation Army from January 2017 to April 2020 were retrospectively analysed. Patients undergoing NACT were divided into the pCR group (80 cases with complete remission or partial remission) and the non-pCR group (46 cases with stable disease or progressive disease) in accordance with their treatment outcome. The pathologic and clinical data of the patients were collected and analysed to identify the factors affecting efficacy of NACT for stage IIIa-N2 NSCLC, and to evaluate the predictive value of PNI and SII in determining the efficacy of NACT. The patients were followed up for 3 years to observe the overall survival, and Cox regression analysis was employed to identify the risk factors affecting patient survival. Furthermore, the effect of PNI and SII on the survival time was analysed. RESULTS: Multivariate regression analysis showed that tumor diameter, PNI, and SII were influencing factors for poor efficacy of NACT in patients with stage IIIa-N2 NSCLC. The non-pCR group exhibited a higher mortality within 3 years, thus a lower 3-year overall survival rate than the pCR group (P<0.05). Cox regression analysis revealed that both PNI and SII were risk factors for poor prognosis in patients with stage IIIa-N2 NSCLC undergoing NACT. Further analysis found a lower 3-year survival rate in patients with low PNI and high SII than in counterparts (P<0.05). CONCLUSION: Tumor diameter, PNI and SII are risk factors for poor efficacy in patients with stage IIIa-N2 NSCLC undergoing NACT. Low PNI and high SII can indicate a poor prognosis in these patients.
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Background: Pathogenic constitutional APC variants underlie familial adenomatous polyposis, the most common hereditary gastrointestinal polyposis syndrome. To improve variant classification and resolve the interpretative challenges of variants of uncertain significance (VUS), APC-specific ACMG/AMP variant classification criteria were developed by the ClinGen-InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP). Methods: A streamlined algorithm using the APC -specific criteria was developed and applied to assess all APC variants in ClinVar and the InSiGHT international reference APC LOVD variant database. Results: A total of 10,228 unique APC variants were analysed. Among the ClinVar and LOVD variants with an initial classification of (Likely) Benign or (Likely) Pathogenic, 94% and 96% remained in their original categories, respectively. In contrast, 41% ClinVar and 61% LOVD VUS were reclassified into clinically actionable classes, the vast majority as (Likely) Benign. The total number of VUS was reduced by 37%. In 21 out of 36 (58%) promising APC variants that remained VUS despite evidence for pathogenicity, a data mining-driven work-up allowed their reclassification as (Likely) Pathogenic. Conclusions: The application of APC -specific criteria substantially reduced the number of VUS in ClinVar and LOVD. The study also demonstrated the feasibility of a systematic approach to variant classification in large datasets, which might serve as a generalisable model for other gene-/disease-specific variant interpretation initiatives. It also allowed for the prioritization of VUS that will benefit from in-depth evidence collection. This subset of APC variants was approved by the VCEP and made publicly available through ClinVar and LOVD for widespread clinical use.
