scholarly journals Real-World Analysis of the Impact of Radiotherapy on Immunotherapy Efficacy in Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2800
Author(s):  
Amir Onn ◽  
Teodor Gottfried ◽  
Amos Stemmer ◽  
Sarit Appel ◽  
Yaacov R. Lawrence ◽  
...  

Background: Immunotherapy (IO) provides a significant benefit for a subgroup of non-small cell lung cancer (NSCLC) patients. Radiotherapy (XRT) might enhance the efficacy of IO. We evaluated the impact of the specifics of XRT treatments on the OS of IO-treated NSCLC patients. Methods: Metastatic NSCLC patients treated with IO were retrospectively identified. Parameters included demographics, tumor characteristics, IO and XRT details. Correlation between the parameters and OS was tested with Cox regression. Results: 453 patients were included. No XRT was given to 167 (36.9%) patients, whereas XRT prior and after IO had 182 (40.2%) and 104 (22.9%) patients, respectively. XRT total doses between 30 and 40 Gy had better overall survival (OS) compared to non-irradiated patients (hazard ratio (HR) 0.5, 95% CI 0.25–1.0, p = 0.049). Worse outcome was seen with total doses ≤ 10 Gy (HR 1.67, 95% 1.13–2.5, p = 0.01), XRT fractions of 4.1–8 Gy (HR 1.48, 95% CI 1.05–2.1, p = 0.027) and XRT to the bone (HR 1.36, 95% CI 1.01–1.8, p = 0.04). Several clinical parameters correlated with OS in the univariate analysis of the IO-treated patients. While, in the multivariate analysis, only ECOG-PS, treatment line, type of IO, albumin and NLR remained statistically significant. Conclusion: Specific doses, fractions and sites of XRT correlated with the OS of IO-treated NSCLC patients in the univariate analysis, although not in the multivariate analysis.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20076-e20076
Author(s):  
Shruti Bhandari ◽  
Danh Pham ◽  
Rohit Kumar ◽  
Jeremy T Gaskins ◽  
Goetz H. Kloecker

e20076 Background: Small cell lung cancer (SCLC) is an aggressive disease currently treated as soon as possible given its rapid doubling time. Evidence for appropriate timing of chemotherapy from diagnosis (TCD) for SCLC is lacking. This study evaluates TCD in SCLC on a national level. Methods: National Cancer Database identified SCLC patients treated with chemotherapy from 2010 - 2014. Factors associated with TCD were identified with multiple linear regression analyses. TCD was categorized into four groups using cutoff points of 7, 14, and 28 days. Using these categories, median overall survival (MOS) and log-rank test was used for univariate analysis of the survival outcome and the Cox model for multivariate analysis. Results: Among the 64491 SCLC, 42% received chemotherapy alone, 38% chemotherapy followed by radiation and 20% radiation followed by chemotherapy. Median TCD is 14 days with 21% treated within 7d, 21% 8-14d, 30% 15-28d and 28% > 28d from diagnosis. Age, race, insurance, comorbidities and stage were associated with TCD (Table). Significant difference in survival was found by TCD categories (P < .001). MOS for TCD within 7d was 8.2m, 8-14d was 9.2m, 15-28d was 10.3m, and > 28d was 10.8m. In the multivariate analysis, increased TCD was associated with better survival across all stages. Among stage IV patients, compared to those treated within 1 week, the HR is 0.92 (P < .001) for 1-2 weeks, HR 0.82 (P < .001) for 2-4 weeks, and HR 0.77 (P < .001) for > 4 weeks. Results are similar for Stage III and for Stage I/II. Conclusions: These results show a trend towards poor survival with early treatment. While we do not suggest delaying treatment for SCLC patients, our results provide new evidence to inform a discussion about appropriate treatment timing and individualizing treatment. Optimization of patients' clinical baseline before hasty cytotoxic treatment may lead to better outcomes. [Table: see text]


2020 ◽  
Author(s):  
Yu Bai ◽  
Xu Ma ◽  
Sen Han ◽  
Jian Fang

Abstract Background: Patients with non-small cell lung cancer (NSCLC) have a significantly higher risk of developing venous thromboembolism (VTE), a condition that significantly influences the prognosis of these patients. However, the impact of VTE on the survival of NSCLC patients remains unclear. We aim to evaluate the impact of VTE on the mortality of patients with NSCLC. Methods: We systematically reviewed all indexed studies examining the prognosis of NSCLC patients with VTE. Web of Science, EMBASE, PubMed, and the Cochrane Library were searched through December 31, 2019 to identify relevant studies. Fixed- or random-effects models were chosen based on heterogeneity. Results: Twelve articles with 6480 patients were included in this analysis. The heterogeneity of these studies was significant (I2=81%, P<0.01). The overall survival (OS) of NSCLC patients with VTE was shorter compared to patients without VTE (HR=1.71, 95% CI [1.39–2.10], P<0.01). Two small groups of SCLC patients were excluded and the remaining patients were divided into the Asian and non-Asian groups. The Asian group showed low heterogeneity (I2=35%, P=0.20), in which NSCLC patients with VTE also had shorter OS (HR=1.49, 95% CI [1.19–1.88], P<0.01). Conclusions: VTE is significantly associated with a shorter OS of NSCLC patients, especially in Asian patients. Proper prevention and management of VTE is the key to improving the survival of patients with NSCLC.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21601-e21601
Author(s):  
Riccardo Lobefaro ◽  
Giuseppe Viscardi ◽  
Raimondo Di Liello ◽  
Giacomo Massa ◽  
Maria Lucia Iacovino ◽  
...  

e21601 Background: The introduction of Immunotherapy (IO) has dramatically improved the prognosis of patients (pts) with advanced Non-Small Cell Lung Cancer (NSCLC). However, data regarding the role of IO in ECOG Performance Status (PS) 2 pts are generally limited in randomized trials, and real-world evidences could support clinical decision-making. Methods: We retrospectively analyzed data about pts with stage IV NSCLC treated with IO between April 2013 and December 2019 in two Italian Centers. The aim of our study was to assess the impact of PS status (0-1 vs 2) on disease control rate (DCR), progression-free survival (PFS) and overall survival (OS). Response was classified according to RECIST v1.1 criteria. PFS and OS were estimated by the Kaplan-Meier method. Chi-square test was used to compare clinical-pathological variables: gender, age ( < 70, 70-79, ≥80 years-old), smoking status, histology (squamous, non-squamous), PDL1 expression ( < 1%, ≥1%), IO line (1°, ≥2°), number (N) of metastatic sites (1, ≥2), presence of liver and/or brain metastasis. Their impact on survival was evaluated through Cox proportional hazard models. Results: Four-hundred-one pts (35.7% female) with median age of 65.4 years (range 27-88) were studied. Baseline PS was 0 in 134 pts (33.4%), 1 in 209 pts (52.1%) and 2 in 58 pts (14.5%). 312 pts had non-squamous NSCLC, 89 squamous NSCLC. Clinical-pathological variables were uniformly distributed across PS groups except for a higher rate of liver metastasis in PS2 pts ( p= 0.046). Response evaluation was available for 386 pts. DCR was 49.7% in PS0-1 pts and 25.9% in PS2 pts ( p= 0.006). At a median follow-up of 29 months (mos), median PFS was 3.0 mos (95% CI 2.63-4.00) and 2.04 mos (95% CI 1.84-3.00) in pts with PS0-1 and 2 ( p< 0.0001). Median OS was 13.2 mos (95% CI 11.18-15.78) and 4.0 mos (95% CI 2.66-5.62) in pts with PS 0-1 and 2 respectively ( p< 0.0001). Univariate analysis showed significant correlation of PS2 status, negative PDL1, IO line ≥2, N of metastatic sites ≥2 and liver metastasis, for both PFS and OS. Multivariate analysis confirmed an independent association of PS ( p= 0.0013 for PFS, p< 0.0001 for OS), PDL1 ( p= 0.0002 for PFS, p= 0.02 for OS) and liver metastasis ( p= 0.017 for PFS, p= 0.02 for OS). The incidence of Grade 3/4 adverse events was 10.5% in PS 0-1 pts and 13.7% in PS 2 pts ( p= 0.41). Conclusions: Our data confirm reduced efficacy of IO in pts with poor PS, regardless of the N of prior therapy lines or PDL1 expression. Despite IO appears to be safe and tolerable its role remains uncertain in PS2 pts based on worse survival outcomes.


2021 ◽  
Vol 11 ◽  
Author(s):  
Keiko Tanimura ◽  
Tadaaki Yamada ◽  
Ayaka Omura ◽  
Shinsuke Shiotsu ◽  
Nobutaka Kataoka ◽  
...  

BackgroundIn recent years, immune checkpoint inhibitors (ICIs) in combination with chemotherapy have increased survival in patients with advanced non-small cell lung cancer (NSCLC). Vascular endothelial growth factor (VEGF), which plays a key role in tumor angiogenesis, is an immunological modulator; therefore, it is expected that anti-VEGF therapy in combination with ICIs enhances the antitumor effect of ICIs. In the present study, we investigated the impact of VEGF inhibition on clinical outcomes of NSCLC patients, including the efficacy of ICI treatment.MethodsA total of 105 patients with advanced NSCLC who had been treated with ICIs were retrospectively analyzed to examine the relationship between the history of treatment with anti-VEGF agents and the clinical outcomes with ICI monotherapy.ResultsPatients who had received anti-VEGF therapy prior to ICIs showed shortened progression-free survival of ICI treatment and a decreased overall response rate to ICI treatment. By contrast, anti-VEGF therapy after ICI treatment was associated with increased survival, especially in patients who had also received anti-VEGF therapy prior to ICI therapy.ConclusionsThese retrospective observations suggest that anti-VEGF therapy prior to ICIs might be a negative predictor of response to ICIs. The sequence of anti-VEGF therapy might play a role in its ability to predict survival in NSCLC patients. Further investigation is warranted to identify the role of VEGF inhibition in altering clinical outcomes after immunotherapy.


2021 ◽  
Vol 10 ◽  
Author(s):  
Xin Sui ◽  
Leilei Jiang ◽  
Huajing Teng ◽  
Lan Mi ◽  
Bo Li ◽  
...  

PurposeTo identify cytokines in plasma that may predict objective response and progression-free survival (PFS) in patients with locally advanced non-small cell lung cancer (NSCLC) treated with chemoradiotherapy.Materials and MethodsFrom April 2016 to May 2017, thirty-one patients with locally advanced inoperable/unresectable NSCLC were included, and treated with concurrent chemoradiotherapy (CCRT). No immune checkpoint inhibitors were administered after CCRT. Plasma from each patient was collected before radiotherapy, and 25 cytokines in the plasma were measured by Luminex or U-PLEX assays. Logistic regression and COX regression were performed to identify the predictive factors for objective response and PFS, respectively. Kaplan-Meier survival analysis was used to compare the PFS between the groups.ResultsHigh levels of IL-13 and TNF-α, and low levels of ICAM-1, IFN-γ, and soluble PD-L1 (sPD-L1) were significantly associated with objective response (P &lt;0.05). High levels of IL-8, CCL5, and CXCL3 also showed a trend toward association with objective response (P &lt;0.1). The combination of cytokines (IL-8 and ICAM-1, or TNF-α and sPD-L1) improved predictive accuracy. Univariate analysis identified IL-8 and ICAM-1 as potential markers to predict PFS. Multivariate analysis suggested that high level of IL-8 (P =0.010) and low level of ICAM-1 (P =0.011) correlated significantly with a longer PFS.ConclusionIL-8 and ICAM-1 in plasma have the potential to predict objective response and PFS in patients with locally advanced NSCLC underwent chemoradiotherapy.


2020 ◽  
Author(s):  
Yaji Yang ◽  
Shusen Sun ◽  
Feng Xiong ◽  
Yin Xiao ◽  
Jing Huang

Abstract Background Predictive models to determine the prognosis of elderly patients with Stage I small-cell lung cancer (SCLC) are lacking. This study aimed to establish a useful nomogram for predicting the cancer-specific survival (CSS) of elderly patients with Stage I SCLC.MethodsUsing the Surveillance, Epidemiology, and End Results registry database, we identified patients aged ≥ 65 years with pathological AJCC (American Joint Committee on Cancer) Stage I SCLC from 2004 to 2014. The CSS was evaluated by the Kaplan-Meier method. Patients were divided into training and validation cohorts. In the training cohort, univariate analysis and multivariate analysis by the Cox proportional hazards regression identified risk factors that predicted CSS and the results were used to formulate a nomogram for the 1-, 3-, and 5-year CSS rates of elderly patients with Stage I SCLC. The performance of the nomograms was internally and externally validated by the bootstrap resampling.Results: In total, we extracted 1,623 elderly patients with Stage I SCLC. The median CSS was 34 months, and the 5-year CSS was 41 months. Multivariate analysis revealed that age, histologic type, tumor size, and AJCC Stage were significant predictors of CSS. A nomogram was formulated based on the results of multivariate analysis. The C-indices of the nomogram for training and validation cohorts were 0.68 and 0.62, indicating that the nomogram exhibited a sufficient level of discrimination. The calibration curves demonstrated good agreement between the nomogram prediction and actual observation.Conclusion:A practical nomogram to predict the CSS of elderly patients with Stage I SCLC is constructed. The predictive tool is helpful for patient counseling and treatment decision making.


2021 ◽  
Vol 11 ◽  
Author(s):  
Sameh Daher ◽  
Yaacov R. Lawrence ◽  
Elizabeth Dudnik ◽  
Ekaterina Hanovich ◽  
Damien Urban ◽  
...  

ObjectivesWe aimed to examine clinical data and baseline blood test results as potential predictive biomarkers for benefit from nivolumab, in advanced non-small cell lung cancer patients (NSCLC).Materials and MethodsA chart review was performed of 108 advanced NSCLC patients who commenced treatment with nivolumab between 2015-6 at three Israeli cancer centers, and for whom laboratory tests results were available. Data collected included sex, age, ECOG-PS, histology and number of previous lines of treatment. Baseline blood test results collected: absolute lymphocyte and neutrophil count (ANC), white blood cells (WBC), hemoglobin, platelets, albumin and lactate dehydrogenase (LDH). Neutrophil to Lymphocyte Ratio and ‘derived NLR’ (dNLR = (ANC/[WBC-ANC])) were calculated. Disease control at six months (DC6) was defined as any tumor shrinkage or stable disease during the first six months of nivolumab treatment. The association between clinical/laboratory variables and survival was tested with a Cox proportional hazard model. Data cut-off occurred in November 2019.Results35 patients (32.4%) achieved DC6. Median overall survival (OS) of entire study population was 5.4 months. Four year survival rate was 16%. Achievement of DC6 strongly correlated with longer OS (HR 0.12, 95% C.I. 0.07-0.21, p&lt;0.001). In univariate and multivariate analysis, dNLR, albumin and LDH correlated significantly with OS. No variables correlated significantly with DC6 in multivariate analysis. Based on albumin and LDH, we produced a score called CLAS (combined LDH and albumin score), including four prognostic groups of patients. Patients having low albumin and high LDH had the worst prognosis.ConclusionIn real-life setting, long-term efficacy of nivolumab in advanced line treatment of NSCLC is consistent with clinical trials. Response or stability of disease during first six months of treatment is associated with prolonged survival. We propose a novel score (CLAS) that may be useful for predicting outcome in nivolumab-treated NSCLC patients, but further validation is required.


2021 ◽  
Vol 12 ◽  
Author(s):  
Dani Xiong ◽  
Chuanlin Wang ◽  
Zhaohui Yang ◽  
Fusen Han ◽  
Huaibing Zhan

Background: In this study, we aimed to explore the diagnostic potential of serum-based exosomal long intergenic noncoding RNA 917 (LINC00917) in non-small cell lung cancer (NSCLC).Methods: Exosomes were extracted from NSCLC patients’ serum samples. Exosomal LINC00917 expression levels were compared, by qRT-PCR, between cancer patients and healthy controls, as well as sub-populations of cancer patients. The association between exosomal LINC00917 expression and NSCLC patients’ clinicopathologic factors were investigated, and receiver operating characteristic (ROC) curves were drawn. In addition, NSCLC patients’ overall survivals (OSs) was examined based on exosomal LINC00917 expression and further evaluated by the cox regression analysis.Results: Serum-derived exosomal LINC00917 was highly expressed in NSCLC patients, and further upregulated in stage III/IV cancer patients. Exosomal LINC00917 yielded modestly good under the curve (AUC) values. Upregulated exosomal LINC00917 expression was closely associated with cancer patients’ advanced stages and shorter OSs.Conclusion: Serum-derived exosomal LINC00917 may hold diagnostic potential for patients with non-small cell lung cancer.


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18113-e18113
Author(s):  
Junior S Torres-Roman ◽  
Claudio J. Flores ◽  
Alfredo Aguilar ◽  
Denisse Bretel ◽  
Christian Diego Rolfo ◽  
...  

e18113 Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. It is well known that there are differences in the outcome between genders; however the effects of the sex in the prognosis have not been previously properly defined. Our aim was to evaluate in a meta-analysis, differences in healthcare outcomes between women and men with NSCLC in terms of overall survival (OS) and progression-free survival (PFS). Methods: We searched for references of published studies of hospitalary databases indexed in PubMed/Medline. We retrieved 67 references (from 1989 to 2016), of which eleven references were eligible for data extraction. In total, 11 references were evaluable for OS. Meta-analysis for Hazard Ratios (HR) obtained from univariate and multivariate analysis were analyzed in different groups. The meta-analysis was done in the software Review Manager 5.3. Results: In total, 7 studies had information for OS univariate analysis, 7 studies for OS multivariate analysis, only, one for PFS univariate analysis and one for PFS multivariate analysis. The meta-analysis for OS univariate analysis resulted in a HR = 0.75 (P < 0.00001; 95% CI: 0.71 to 0.79) for women compared to men, although there was a high statistical heterogeneity between cohorts (P < 0.0001). In the meta-analysis for OS multivariate analysis was estimated a HR = 0.75 (P < 0.00001; 95% CI: 0.73 to 0.78), with statistical heterogeneity between cohorts (P = 0.0005). Conclusions: Our study quantified a 25%-risk reduction of death for women with NSCLC compare with male men patients with the same diagnosis.


2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21732-e21732
Author(s):  
Lin Wu ◽  
Meilin Jiang ◽  
Wenying Peng ◽  
Xingxiang Pu ◽  
Bolin Chen ◽  
...  

e21732 Background: Selecting patients that potentially benefit from immune checkpoint inhibitors (ICIs) is critical. Programmed death ligand-1 (PD-L1) protein immunohistochemical expression on cancer cells or immune cells and Next generation sequencing based tumor mutational burden (TMB) are the hot spots in studies on ICIs, but there is still confusion in the testing methods. Due to blood samples are much easier for clinical application, many potential peripheral biomarkers have been proposed. This study identify blood parameters that associated with outcome of non-small cell lung cancer (NSCLC) patients with ICIs monotherapy. Methods: Data of 76 NSCLC patients were analyzed retrospectively. To assess the connection between survival and peripheral blood markers measured before and after treatment, we utilized COX regression model survival analysis and receiver operating characteristic (ROC) curve to assess the markers. Results: In the nivolumab cohort, the optimal cutoff for predicting 11 month overall survival (OS) were 168.13 and 43g/L in Plateletto-lymphocyte ratio (PLR) and albumin, respectively. When patients are grouped with PLR and albumin the cut-offs, a significant difference in SD-PR vursus PD rate were found between high and low groups, separately. which was not found when grouped by PD-L1 expression. Patients with high PLR ( > 168.13) or low albumin ( < = 43g/L) before ICI had a significantly raised hazard of progression, separately (for PLR, P = 0.006; for albumin, P = 0.033) and of death (for PLR, P = 0.014; for albumin, P = 0.009) compared with those patients who had low PLR or albumin level. More importantly, we found that higher PLR ( > 168.13) after the fourth cycle of ICIs was also an prognostic biomarker, which significantly correlated with shorter OS in both Nivolumab (P = 0.046) and durvalumab cohort (P = 0.028). Conclusions: PLR and albumin may help the stratification of high progression and death risk group in advanced NSCLC patients treated with nivolumab and durvalumab monotherapy.


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