Background
Re‐biopsy is important for exploring resistance mechanisms, especially for non‐small cell lung cancer (NSCLC) patients who develop resistance to EGFR‐tyrosine kinase inhibitors (TKIs). Liquid biopsy using circulating tumor DNA has come into use for this purpose. This retrospective study investigated the status of re‐biopsy and liquid biopsy in NSCLC patients with
EGFR
mutations and evaluated their effect on clinical strategies and prognosis.
Methods
Five hundred fifty‐five NSCLC patients with resistance to EGFR‐TKIs were included and divided into three groups: re‐biopsy, liquid biopsy, and no re‐biopsy. Amplification refractory mutation system (ARMS) PCR or super ARMS PCR was used to detect
EGFR
mutations.
Results
Three hundred eight (55.5%) patients underwent re‐biopsy; 45.5% (140/308) were positive for T790M. The most common re‐biopsy procedure was computed tomography‐guided percutaneous core needle biopsy (60.1%), followed by effusion drainage (29.5%) and superficial lymph node biopsy (6.5%). One hundred eighteen (21.3%) patients underwent liquid biopsy; the T790M detection rate was 41.5% (49/118.) Of the 308 patients who underwent re‐biopsy, 69 were examined for
EGFR
mutations with plasma. The concordance rate of T790M detection between tissue and plasma was 66.7%. A statistical difference in further treatment after EGFR‐TKI failure was observed among all groups (
P
= 0.014). Patients in the biopsy groups were more likely to receive third‐generation EGFR‐TKIs. Multivariate analysis showed that re‐biopsy had a significant impact on overall survival (
P
< 0.001).
Conclusion
Re‐biopsy plays a pivotal role in the management of patients with NSCLC and resistance to EGFR‐TKIs. Liquid biopsy may be an alternative if difficulties performing re‐biopsy exist.
BackgroundPeripheral blood biomarkers to immunotherapy have attracted more and more attentions owing to noninvasive nature. This study was designed to identify a panel of tumor associated autoantibodies (TAAbs) in plasma to predict the clinical outcome of ICIs-based treatment in advanced NSCLC patients and correlation between TAAbs and checkpoint inhibitor pneumonitis (CIP) would also be investigated.Materials and MethodsBaseline plasma was collected from patients with advanced NSCLC before receiving ICIs-based treatment. ELISA was used to detect concentration of autoantibodies. Clinical efficacy was evaluated according to RECIST v1.1.ResultsWe have identified a panel of five-TAAbs to predict responses of ICIs-based treatment in a discovery cohort (n = 37), and confirmed its predictive value in a validation cohort (n = 129). In the validation cohort, the positivity of this 5-TAAbs panel was significantly associated with better response (ORR: 44.4% vs. 13.6%, P < 0.001) and longer PFS (7.6 vs. 3.3m, P < 0.001). This significant association was remained in subgroup of patients treated with combination therapy (ORR: 43.8% vs. 13.7%, P = 0.004,PFS: 6.7 vs. 3.7m, P = 0 .017). Furthermore, this 5-TAAs panel worked better in patients who received subsequent-line treatment (ORR: 42.4% vs. 7.7%, P = 0.001, PFS: 6.2 vs. 3.0m, P = 0.004) than those received first-line treatment (ORR: 46.7% vs. 35.7%, P = 0.345, PFS: NR vs. 10.48m, P = 0.146). In addition, the CIP incidence in patients with 5-TAAbs positive was significantly higher comparing to negative patients (20.4% vs. 5.9%, P = 0.015).ConclusionOur 5-TAAbs panel is a potential predictive biomarker for responses and toxicities to ICIs-based treatment in patients with advanced NSCLC.
Background: Recent studies have suggested obesity could contribute to improved outcomes of immune checkpoint inhibitor (ICI)-based treatment. Non-alcoholic fatty liver disease (NAFLD), the most common form of chronic liver disease, is also obesity-related, but its association with the efficacy of ICI-based treatment has not yet been reported.
Methods:We retrospectively reviewed the medical records of advanced non-small cell lung cancer (NSCLC) patients treated at Shanghai Pulmonary Hospital between June 2015 and June 2019. NAFLD was confirmed by ultrasound examination of the abdomen. The efficacy of ICI-based treatment was evaluated based on Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Univariate analysis to compare progression-free survival (PFS) was conducted using the log-rank test. Multivariate analysis was performed using the Cox proportional hazards model.Results: A total of 223 patients with advanced NSCLC who received ICI-based treatment were included in the study, of whom 26.9% (n=60) were confirmed to have NAFLD. Patients with NAFLD were more inclined to to have non-squamous carcinoma and higher body mass index (BMI) compared with those without NAFLD. The median PFS of the entire cohort of patients was 6.6 months. Nno significant difference was found in response [objective response rate (ORR) 43.3% vs. 35.6%, P=0.289, disease control rate (DCR) 83.3% vs. 75.5%, P=0.211], nor in PFS (7.0 vs. 6.6 months, P=0.769) between the patients with (n=60) and without NAFLD (n=163). Surprisingly, in the subgroup of patients with liver metastases (LMs), there were dramatically significant differences in ORR (71.4% vs. 9.1%, P=0.013), DCR (85.7% vs. 18.2%, P=0.013), and median PFS [5.1 vs. 2.1 months, P=0.014, hazard ratio (HR): 0.244] between patients with (n=7) and without (n=11) NAFLD. Multivariate analysis revealed NAFLD to have a significant impact on PFS (P=0.017) in patients with LMs. In addition, the DCR of LMs was significantly higher in patients with NAFLD compared to those who did not have NAFLD (DCR: 42.9% vs. 0.0%, P=0.038).
Conclusions:In conclusion, NAFLD holds no clinical benefit for advanced NSCLC patients who undergo ICI-based treatment, but it is associated with improved outcomes in patients with LMs.
Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a crucial protein involved in the metabolism of low-density lipoprotein cholesterol. However, the role of plasma PCSK9 in predicting the efficacy of ICIs in advanced non-small cell lung cancer (NSCLC) remains to be clarified. Methods: We retrospectively reviewed the medical records of NSCLC patients who presented at Shanghai Pulmonary Hospital between April 2019 and June 2020. ELISA was conducted to detect the concentration of PCSK9. Clinical efficacy was evaluated according to Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Results: A total of 55 patients were enrolled in the study. The median progression-free survival (PFS) following treatment with ICIs in all patients was 9.9 months. The optimal threshold of baseline plasma PCSK9 was 232.2 ng/ml. Patients with low baseline plasma PCSK9 had a longer PFS (NR vs. 7.37 months, p = 0.017, HR = 0.207, 95% CI: 0.086-0.498) and a better response (ORR 71.4% vs. 43.9%, p = 0.075, DCR 100% vs. 80.5%, p = 0.098) to ICIs. Younger patients (≤66 years) with a lower PCSK9 had a significantly longer PFS and higher treatment response than those with a high baseline level of PCSK9 (NR vs. 5.83 months, p = 0.021, HR = 0.134, 95% CI: 0.044-0.409; ORR 66.7% vs. 30.0%, p = 0.106, DCR 100% vs. 75%, p = 0.153). The situation was similar in patients who received first-line therapy (NR vs. 8.97 months, p = 0.022, HR = 0.138, 95% CI: 0.047-0.400; ORR 63.6% vs. 46.4%, p = 0.480, DCR 100% vs. 89.3%, p = 0.545). Multivariate analysis showed that low PCSK9 concentration was independently associated with PFS (p = 0.032, HR = 0.201). Conclusions: Low baseline plasma PCSK9 level may predict good outcomes in patients with advanced NSCLC treated with ICIs.K E Y W O R D S biomarker, immune checkpoint inhibitors (ICIs), non-small cell lung cancer (NSCLC), proprotein convertase subtilisin/kexin type 9 (PCSK9) † Authors contributed equally.
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