F-087PREOPERATIVE LOW BODY MASS INDEX AND ELEVATED SERUM C-REACTIVE PROTEIN ARE RISK FACTORS FOR THE MORTALITY AFTER LUNG RESECTION OF NON-SMALL-CELL LUNG CANCER IN SMOKERS

e21107 Background: C-Reactive Protein (CRP) is a non-specific inflammatory marker and reflects tissue destruction seen in metastatic cancer (ca). We have observed a tight correlation with CRP trends mirroring ca activity, hence it may prove to be a valuable marker to monitor response to Immuno-Oncology (IO) in non-small cell lung cancer (NSCLC) patients (pts). Once CRP levels stabilized, IO discontinuation was offered, and consenting pts were closely observed. This strategy resulted in shortened IO duration and impressive treatment-free progression-free survival (tf-PFS). We sought to examine the validity of this strategy using the rate of return to any form of ca therapy within 6 months after stopping IO. Methods: We analyzed all pts of a single provider since 2016 with stage IV NSCLC who had CRP checked while on IO, totaling 23 pts. We excluded pts who stopped IO for reasons besides stable CRP values (5 progressed on IO, 3 died while on IO, 1 had side effects, 1 stopped for a clinical trial, 1 opted to complete 2 years of IO, and 2 are still on IO). Of the remaining 10 patient cohort, all pts were males treated at the VA with ages between 56-75 years at diagnosis. 50% of the cohort had adenocarcinoma and 50% had squamous cell carcinoma. Results: Using the CRP trend to shorten the duration of IO resulted in durable drug-free holidays with none of the cohort returning to any form of ca therapy within 6 months and comparable rates of overall survival (OS) despite shorter IO duration. In KEYNOTE-042, the median OS for pts on the pembrolizumab arm was 16.7 months in the overall population and 20 months in the TPS ≥50% subgroup. Pts were treated for up to 35 months. In our cohort, median OS was 38 months, with all pts currently still alive, and median number of doses of IO was 9 cycles, or approximately 7 months. Our pts had ongoing progression free survival (PFS) after stopping treatment, which we report as tf-PFS. The median tf-PFS of our cohort was 23.5 months. Conclusions: In pts with stage IV NSCLC treated with IO, CRP appears promising as a marker to tailor IO therapy addressing tumor and clinical heterogeneity. Responding pts with stable CRP levels can be safely taken off IO. CRP should be monitored with stable values indicating continued PFS. tf-PFS rather than PFS may serve as a surrogate for cure and carries significant impact for pts financially, socially, and psychologically. [Table: see text]

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Postoperative C-reactive Protein Is a Predictive Biomarker for Survival After Non-small Cell Lung Cancer Resection

Anticancer Research ◽

10.21873/anticanres.13334 ◽

2019 ◽

Vol 39 (4) ◽

pp. 2193-2198 ◽

Cited By ~ 4

Author(s):

SHUICHI SHINOHARA ◽

RYO OTSUKI ◽

TAKAMITSU ONITSUKA ◽

KAZUHIKO MACHIDA ◽

MASAKI MATSUO ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Predictive Biomarker ◽

Small Cell ◽

C Reactive Protein ◽

Small Cell Lung ◽

Cancer Resection ◽

Reactive Protein

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C-Reactive Protein (CRP) Levels in Immune Checkpoint Inhibitor Response and Progression in Advanced Non-Small Cell Lung Cancer: A Bi-Center Study

Cancers ◽

10.3390/cancers12082319 ◽

2020 ◽

Vol 12 (8) ◽

pp. 2319

Author(s):

Jakob M. Riedl ◽

Dominik A. Barth ◽

Wolfgang M. Brueckl ◽

Gloria Zeitler ◽

Vasile Foris ◽

...

Keyword(s):

Lung Cancer ◽

Validation Cohort ◽

External Validation ◽

Small Cell ◽

C Reactive Protein ◽

Small Cell Lung ◽

Discovery Cohort ◽

Reactive Protein ◽

Progression Risk ◽

Center Study

Background: Biomarkers for predicting response to immune checkpoint inhibitors (ICI) are scarce and often lack external validation. This study provides a comprehensive investigation of pretreatment C-reactive protein (CRP) levels as well as its longitudinal trajectories as a marker of treatment response and disease outcome in patients with advanced non-small cell lung cancer (NSCLC) undergoing immunotherapy with anti PD-1 or anti PD-L1 agents. Methods: We performed a retrospective bi-center study to assess the association between baseline CRP levels and anti PD-(L)1 treatment outcomes in the discovery cohort (n = 90), confirm these findings in an external validation cohort (n = 101) and explore the longitudinal evolution of CRP during anti PD-(L)1 treatment and the potential impact of dynamic CRP changes on treatment response and disease outcome in the discovery cohort. Joint models were implemented to evaluate the association of longitudinal CRP trajectories and progression risk. Primary treatment outcomes were progression-free survival (PFS) and overall survival (OS), while the objective response rate (ORR) was a secondary outcome, respectively. Results: In the discovery cohort, elevated pretreatment CRP levels emerged as independent predictors of worse PFS (HR per doubling of baseline CRP = 1.37, 95% CI: 1.16–1.63, p < 0.0001), worse OS (HR per doubling of baseline CRP = 1.42, 95% CI: 1.18–1.71, p < 0.0001) and a lower ORR ((odds ratio (OR) of ORR per doubling of baseline CRP = 0.68, 95% CI: 0.51–0.92, p = 0.013)). In the validation cohort, pretreatment CRP could be fully confirmed as a predictor of PFS and OS, but not ORR. Elevated trajectories of CRP during anti PD-(L)1 treatment (adjusted HR per 10 mg/L increase in CRP = 1.22, 95% CI: 1.15–1.30, p < 0.0001), as well as a faster increases of CRP over time (HR per 10 mg/L/month faster increase in CRP levels = 13.26, 95% CI: 1.14–154.54, p = 0.039) were strong predictors of an elevated progression risk, whereas an early decline of CRP was significantly associated with a reduction in PFS risk (HR = 0.91, 95% CI: 0.83–0.99, p = 0.036), respectively. Conclusion: These findings support the concept that CRP should be further explored by future prospective studies as a simple non-invasive biomarker for assessing treatment benefit during anti PD-(L)1 treatment in advanced NSCLC.

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