Baseline systemic inflammatory immune index may predict overall survival and progression-free survival in patients with non-small cell lung cancer patients on immune checkpoint inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21202-e21202
Author(s):  
John P. Palmer ◽  
Yenong Cao ◽  
Samer Ibrahim ◽  
Natasha Dhawan ◽  
Muhammad Zubair Afzal ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
The Mean ◽  
Nsclc Patients

e21202 Background: Increased systemic inflammatory state and increased inflammation within tumor micro-environment (TME) have been associated with a worse prognosis and lower responsiveness to immune checkpoint inhibitors (ICI). Systemic inflammatory immune index (SII) reflects the changes in the systemic inflammatory matrix. Studies have shown the association of SII with cancer survival and treatment outcomes. We aim to study the effect of SII on treatment outcomes in non-small cell lung cancer (NSCLC) patients being treated with ICI. Methods: We conducted a retrospective analysis on 178 NSCLC patients treated with ICIs (pembrolizumab, nivolumab, ipilimumab/nivolumab or atezolizumab) alone or in combination with chemotherapy. SII is the product of platelets multiplied by neutrophils divided by lymphocytes. Baseline and 8-week SIIs were obtained. Radiographic response, duration of radiographic response (date of best response to radiographic progression), overall survival (OS), and progression-free survival (PFS) were evaluated. A high SII was defined as a value greater than the median SII. Cox regression univariate and multivariate analyses were performed. Logistic regression, t-test, and Chi-square tests were applied. Results: Overall, 81% patients had adenocarcinoma and 19% patients had squamous, adenosquamous or large cell carcinoma. The majority of the patients were female (56.2% vs. 43.8%). Median SII at baseline was 1335. The objective response rate (ORR) was 45.1%. The disease control rate was 75.8%. The ORR was 51% in patients receiving ICI first-line compared to 35% in those who received ICI as a second-line therapy. At baseline, there was no difference in the mean SII between responders and non-responders (2146.2 vs. 1917.5, P = 0.5); however at 8 weeks, the mean SII was significantly lower in responders compared to non-responders (1198.8 vs. 2880.2, P = 0.02). A total of 15 (10.9%) patients were found to have pseudoprogression or mixed response on follow-up imaging. Among these, 11(73.3%) patients had low SII at 8 weeks (P = 0.04). The median OS was significantly higher in patients with low SII at baseline (29.6 months vs. 10.1 months, P = 0.001 95% CI 10.6 – 22.1). Similarly, there was a significant difference in median PFS in patients with low SII (14.6 months vs. 6.7 months, P = 0.002, 95% CI 5.6 – 11.6). There was no correlation between high or low SII on the incidence of immune-related adverse events. Conclusions: SII may have significant impact on OS and PFS and could be serially monitored to assess the response to ICI. A low SII may help to differentiate pseudoprogression vs. true progression. Prospective studies are needed to validate these findings. Further, it will be interesting to see if SII could be incorporated into predictive models to determine the duration of cytotoxic therapy in selected patients.

scholarly journals Beyond Abscopal Effect: A Meta-Analysis of Immune Checkpoint Inhibitors and Radiotherapy in Advanced Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2352
Author(s):  
Francesco Fiorica ◽  
Umberto Tebano ◽  
Milena Gabbani ◽  
Mariasole Perrone ◽  
Sonia Missiroli ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Metastatic Nsclc ◽  
Nsclc Patients

Background: Immune checkpoint inhibitors (ICI) plus radiotherapy (RT) have been suggested as an emerging combination in non-small cell lung cancer (NSCLC) patients. However, little is known about the magnitude of its benefits and potential clinical predictors. Objective: To assess the effects of this combination on the increase in overall and progression-free survival. Data sources: The MEDLINE and CANCERLIT (1970–2020) electronic databases were searched, and the reference lists of included studies were manually searched. Study selection: Studies were included if they were comparative studies between combination ICI-RT and ICI or RT alone in advanced or metastatic NSCLC patients. Overall survival (OS) was analyzed according to the treatment strategy. Data extraction: Data on population, intervention, and outcomes were extracted from each study, in accordance with the intention-to-treat method, by two independent observers and combined using the DerSimonian method and Laird method. Results: Compared to ICI or RT alone, ICI-RT significantly increased the 1-year and 3-year OS RR by 0.75 (95% CI 0.64–0.88; p = 0.0003) and 0.85 (95% CI 0.78–0.93; p = 0.0006), respectively. Furthermore, there was a statistically significant benefit on 1- and 3-year progression-free survival (RR 0.73 (95% CI, 0.61–0.87; p = 0.0005) and RR 0.82 (95% CI 0.67–0.99; p = 0.04), respectively). Conclusions: In patients with advanced or metastatic NSCLC, combination ICI-RT increases 1- and 3-year OS and progression-free survival compared to ICI or RT alone.

scholarly journals PIOS (Patras Immunotherapy Score) Score Is Associated with Best Overall Response, Progression-Free Survival, and Post-Immunotherapy Overall Survival in Patients with Advanced Non-Small-Cell Lung Cancer (NSCLC) Treated with Anti-Program Cell Death-1 (PD-1) Inhibitors

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1257
Author(s):  
Foteinos-Ioannis Dimitrakopoulos ◽  
Achilleas Nikolakopoulos ◽  
Anastasia Kottorou ◽  
Fotini Kalofonou ◽  
Elias Liolis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Cell Death ◽  
Prognostic Value ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Nsclc Patients ◽  
Program Cell Death

Immunotherapy with immune checkpoint inhibitors (ICIs) has changed the therapeutic management of advanced non-small cell lung cancer (aNSCLC) over the last decade. However, there is an unmet need for clinically useful biomarkers in this patient subgroup. The aim of this study was to combine baseline clinical characteristics of aNSCLC patients, in the form of a scoring system, and to investigate its predictive and prognostic value in NSCLC patients treated with ICIs. A total of 112 patients with advanced (stages IIIA to IV) NSCLC, treated with nivolumab or pembrolizumab, were enrolled in this study. Patras Immunotherapy Score (PIOS) was developed based on four of the studied parameters (performance status (PS), body mass index (BMI), age, and lines of treatment (LOT), which were incorporated into our formula (PS × BMI/ LOT × age). PIOS score was strongly associated with best overall responses (BOR), with those patients having benefit/good response (stable disease (SD) or partial (PR) or complete response (CR), achieving a higher score compared to patients who developed progressive disease (PD) (p < 0.001). Furthermore, PIOS score was associated with progression-free survival (PFS), since high-score patients had longer PFS (p < 0.001, hazard ratio (HR) = 0.469). Moreover, PIOS was associated with post-immunotherapy overall survival (OS), with high-score patients having improved OS (log-rank p = 0.019). This study suggests that a combination of baseline parameters, which give rise to PIOS score, may predict the best response of NSCLC patients treated with anti-program cell death -1 (PD-1) monotherapy as well as it may have a potent prognostic value for PFS and post immunotherapy OS.

PTPRD/PTPRT mutations as potential positive predictor for response of immune checkpoint inhibitors in non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15112-e15112
Author(s):  
Jian Zeng ◽  
Guoqiang Wang ◽  
Zhengqing Yan ◽  
Hao Zheng ◽  
Jianqiang Li ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Enrichment Analysis ◽  
Small Cell ◽  
Gene Set Enrichment Analysis ◽  
Small Cell Lung ◽  
Gene Set Enrichment ◽  
Nsclc Patients

e15112 Background: Immune checkpoint inhibitors (ICIs) have demonstrated positive results in non-small cell lung cancer (NSCLC) patients, with durable responses and prolonged overall survival (OS). Nevertheless, the response rate to immunotherapy is still limited. It is necessary to identify clinically useful biomarkers that can distinguish patients who can respond to ICIs. PTPRD/PTPRT are the phosphatases of JAK-STAT signaling, which may be associated with response to ICIs. Here we aimed to demonstrate the association between PTPRD/PTPRT and ICIs. Methods: Genomic and survival data of NSCLC patients administrated with anti–PD-1/PD-L1 or anti–CTLA-4 antibodies (Rizvi2015; Hellmann2018; Rizvi2018 Samstein2019) were retrieved from publicly accessible data. Genomic, survival and mRNA data of 1007 patients with NSCLC was obtained from The Cancer Genome Atlas (TCGA). Association between PTPRD/PTPRT mutation and progression-free survival (PFS) and overall survival (OS) were analyzed. Gene set enrichment analysis (GSEA) was used to determine potentially relevant gene expression signatures between specific subgroups. Results: PTPRD/PTPRT mutations were significantly associated with better PFS in Rizvi2015 cohort (HR = 0.16; 95% CI, 0.02-1.17; P = 0.03), Hellmann2018 cohort (HR, 0.49; 95% CI, 0.26-0.94; P = 0.03) and Rizvi2018 cohort (HR = 0.64; 95% CI, 0.44-0.92; P = 0.01). PTPRD/PTPRT mutation was also significantly associated with better OS in Samstein2019 cohort (HR, 0.66; 95% CI, 0.45-0.97; P = 0.03). In TCGA, no association between PTPRD/PTPRT mutations and OS was observed (P = 0.91), suggesting that PTPRD/PTPRT mutations were not prognostic factor. PTPRD/PTPRT mutations were associated with increased TMB (P < 0.0001). The mRNA expression of STAT1 and CD4 was higher in patients with PTPRD/PTPRT mutant type than PTPRD/PTPRT wild type. Gene Set Enrichment Analysis revealed prominent enrichment of signatures related to inflammatory response, interferon gamma response and antigen processing and presentation in patients with PTPRD/PTPRT mutation. Conclusions: Our results suggest that PTPRD/PTPRT mutation is associated with better PFS and OS in NSCLC patients receiving ICIs by increasing immune-related gene signatures. The role of PTPRD/PTPRT in immunotherapy is needed to be further studied.

scholarly journals Patterns of Failure in Patients With Advanced Non-Small Cell Lung Cancer Treated With Immune Checkpoint Inhibitors

2021 ◽  
Vol 11 ◽  
Author(s):  
Rong Chai ◽  
Yipengchen Yin ◽  
Xuwei Cai ◽  
Xiaolong Fu ◽  
Qin Zhang
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Disease Progression ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Small Cell ◽  
Small Cell Lung ◽  
Failure Patterns ◽  
Nsclc Patients

ObjectiveThe advent of immune checkpoint inhibitors (ICIs) has rapidly transformed the treatment paradigm of non-small cell lung cancer (NSCLC). Despite the durability of response to ICIs, the vast majority of patients will later develop progression. However, the failure patterns of ICI treatment are unknown. Here, our study explored the failure patterns in advanced NSCLC patients treated with ICIs.MethodsA cohort of 156 IIIB or IV NSCLC patients treated with first-/second-line ICIs were retrospectively analyzed. Patients who experienced clinical benefit and then developed progression were identified. The disease progression patterns were divided into three categories: progression in new sites, progression in existing sites, and combined progression. The number of progression sites was also recorded.ResultsBefore the cutoff date, 91 (77.1%) patients had experienced disease progression; 34% of patients had progressed in the last 9 months of the first year. Fifty-three (58.2%) patients had developed progression at existing lesions, and 56 (61.5%) patients had shown ≤2 progression sites (oligo-progression). In patients with oligo-progression, the median time of disease progression was 8.23 months and the counterpart (systemic progression) was 5.97 months. The oligo-progression patients showed prolonged median overall survival (27.23 months) compared with patients with systemic progression (18.87 months).ConclusionsFailure patterns of ICI therapy were predominantly “existing” sites, and the most common lesions of progression were the lung and lymph nodes. Most patients experienced oligo-progression which occurred later than systemic progression and showed prolonged overall survival. The control of the local lesions might be beneficial to improve ICI treatment efficacy.

scholarly journals Stereotactic body radiotherapy for early-stage non-small cell lung cancer in patients with subclinical interstitial lung disease.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21050-e21050
Author(s):  
Min Hu ◽  
Xiaojiang Sun ◽  
Yuanjun Liu ◽  
Yaoyao Zhu ◽  
Qinghua Xu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Early Stage ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Early Stage Nsclc ◽  
Nsclc Patients

e21050 Background: Stereotactic body radiotherapy (SBRT) is a highly focused radiation treatment, which is now recommended to treat non-small cell lung cancer (NSCLC) patients with early stage disease. The purpose of this study is to evaluate the efficacy and toxicity of SBRT for early stage NSCLC patients with subclinical interstitial lung disease (ILD). Methods: One hundred and nine patients with early stage NSCLC were treated with SBRT between December 2011 and August 2016 in our institution; patients with subclinical (untreated and oxygen-free) ILD were treated with SBRT, while those with clinical ILD (post- or under treatment) were not. The median SBRT dose was 50 Gy in 5 fractions and the median biologically effective dose (BED; α/β = 10) was 100 Gy (range:72-119 Gy). The presence of subclinical ILD in the pre-SBRT CT findings was reviewed by two chest radiologists. The relationships among the efficacy, radiation pneumonitis (RP) and clinical factors were investigated. Results: Subclinical ILD was recognized in 38 (35%) of 109 patients. Grade 2–4 RP was recognized in 48 (44%) of 109 patients, no Grade 5 RP was happened. Grade 2–4 RP was observed in 17 (45%) of 38 patients with subclinical ILD. Subclinical ILD was not found to be a significant factor influencing Grade 2–4 RP; however, extensive RP beyond the irradiated field, including the contralateral lung, was recognized in only two patients who were both suffering from subclinical ILD, and the rate of extensive RP was significantly high in the patients with subclinical ILD. Dosimetric factors of the lungs (V5, V10, V20, MLD, V12.5, V13.5) were significantly associated with Grade 2–4 RP. The three-year overall survival and progression-free survival rates of all patients were 82.8% and 62.5%, respectively. No significant differences were seen in either overall survival or progression-free survival rates among the patients with ILD and those without ILD, or with RP and those without RP. Conclusions: Subclinical ILD was not found to be a significant factor for Grade 2–5 RP or clinical outcomes in early stage NSCLC treated with SBRT; however, uncommon extensive RP can occur in patients with subclinical ILD.

scholarly journals CMET-01. IMMUNE CHECKPOINT INHIBITORS FOR NON-SMALL CELL LUNG CANCER WITH BRAIN METASTASIS: THE ROLE OF GAMMA KNIFE RADIOSURGERY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi51-vi51
Author(s):  
Min Ho Lee ◽  
Kyung-Rae Cho ◽  
Jung-Il Lee
Keyword(s):  
Lung Cancer ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Gamma Knife Radiosurgery ◽  
Progression Free Survival ◽  
Small Cell ◽  
Small Cell Lung ◽  
Free Survival ◽  
Group A

Abstract PURPOSE Immune checkpoint inhibitors (ICIs) are approved for the treatment of non-small cell lung cancer (NSCLC), but the safety and efficacy of the combined treatment with ICIs and gamma knife radiosurgery (GKS) remain undefined. METHODS We retrospectively reviewed the medical records of patients with brain metastases from NSCLC who were treated with ICIs between January 2015 and December 2017 at our institute. Of the 134 patients identified, 77 who were assessable for brain responses were categorized into three groups based on the medication administered and GKS: Group A, ICI alone; Group B, ICI with concurrent GKS within 14 days; and Group C, ICI with non-concurrent GKS. RESULTS The median follow-up duration after the diagnosis of brain metastases was 19.1 (range, 1–68.7) months. At the last follow-up, 48 patients (62.3%) died. The overall survival was shorter in Group A than in Groups B and C (P=0.001). There were no statistically significant differences in the intracranial disease progression-free survival (P=0.514), local progression-free survival (P=0.358), and complication rates among the three groups. Twelve patients presented with leptomeningeal seeding (LMS) during follow-up. There was a significant difference in the LMS-free duration from the time of administering ICIs (P=0.011) and the diagnosis of metastasis (P< 0.001). CONCLUSION GKS in combination with ICI showed no favorable overall survival outcome in the treatment of brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS.

Sign in / Sign up

Export Citation Format

Share Document