Physiologic colonic uptake of 18F-FDG on PET/CT predicts immunotherapy response and gut microbiome diversity in patients with advanced non-small cell lung cancer (NSCLC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9600-9600
Author(s):  
Lena Cvetkovic ◽  
Claudine Régis ◽  
Valerio Iebba ◽  
Lisa Derosa ◽  
Antoine Leblond ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Gut Microbiome ◽  
Advanced Nsclc ◽  
Surrogate Marker ◽  
Small Cell ◽  
High Uptake ◽  
Small Cell Lung ◽  
Pet Ct

9600 Background: Immune checkpoint inhibitors (ICI) represent the backbone treatment of advanced non-small cell lung cancer (aNSCLC) patients. Emerging evidence suggests increased gut microbiome (GM) diversity is associated with favorable response. Conversely, antibiotic-induced dysbiosis may be associated with deleterious outcomes in patients receiving ICI in multiple retrospective studies and one prospective study. 18F-FDG physiologic colonic uptake on PET/CT increases following treatment with antibiotics and could be a surrogate marker for GM diversity and therefore clinical response. The aim of this study was to determine if 18F-FDG physiologic colonic uptake prior to ICI initiation correlates with outcomes and GM metagenomics in patients with advanced NSCLC. Methods: 71 patients with aNSCLC who underwent PET/CT prior to ICI were identified. For each patient, the colon was manually contoured, SUVmax was measured in each segment of the colon by a nuclear medicine specialist and average SUVmax was calculated for the whole colon. Patients were stratified in two groups according to median colon SUVmax (low vs high uptake). 18F-FDG physiologic colonic uptake was then compared to overall survival (OS), objective response (ORR), and progression-free survival (PFS). For patients with available stool samples (n = 10), GM composition was defined using metagenomics sequencing. Results: 71 patients (54% men, median age: 68 years) with aNSCLC were included in the study and ICI was the first line of therapy in 38% of those patients. The mean colon SUV for the low and high uptake groups were 1.41 (CI 95% 1.35-1.47) and 2.18 (CI 95% 1.90-2.46) respectively. The high uptake group had a higher proportion of non-responders (p = 0.033) and significant shorter PFS (4.1 months vs 11.3 months, p = 0.005). In the caecum, high uptake also correlated with numerically shorter OS (10.82 vs 27.56 months, p = 0.058) compared to low uptake group. Despite the low number of samples, metagenomics sequencing revealed that PLS-DA (Partial Least Squares Discriminant Analysis) for diversity was lower in the high SUV group (p = 0.008). Conclusions: Higher colon SUVmax on pre-ICI FDG PET/CT is associated with worse clinical outcomes and lower baseline GM diversity in patients with advanced NSCLC. Here, we propose that 18F-FDG physiologic colonic uptake on PET/CT could serve as a surrogate marker of GM diversity and predicts clinical outcomes.

Long-term clinical outcomes of ALK inhibitors in patients with ALK-positive advanced non-small cell lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20542-e20542
Author(s):  
Haruyasu Murakami ◽  
Akira Ono ◽  
Kazuhisa Nakashima ◽  
Shota Omori ◽  
Kazushige Wakuda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Alk Inhibitors ◽  
Alk Inhibitor ◽  
Alk Positive

e20542 Background: Anaplastic lymphoma kinase (ALK) inhibitors show high clinical efficacy in patients with ALK-positive advanced non-small cell lung cancer (NSCLC). However, the long-term clinical outcomes remain unknown. Methods: We retrospectively reviewed medical records of patients with ALK inhibitor-naïve ALK-positive advanced NSCLC who initiated alectinib or crizotinib therapy at the Shizuoka Cancer Center between June 2010 and December 2011. Results: This retrospective study included 14 patients (male/female, 5/9; PS 0/1, 6/8; adenocarcinoma/adenosquamous carcinoma, 13/1; smoker/never smoker, 8/6; brain metastasis presence/absence, 5/9; number of prior chemotherapy regimens 0/1/≥2, 1/7/6; alectinib/crizotinib, 4/10) with a median age of 55 years (range, 28-71). At the data cut-off (January 16, 2017), three patients were still receiving first ALK inhibitors (alectinib in two patients and crizotinib in one). One patient requested the discontinuation of alectinib therapy after five years. One patient discontinued crizotinib therapy due to unacceptable toxicity. Nine patients discontinued first ALK inhibitors due to disease progression. The overall response rate was 78.6% with complete response in two patients (14.3%), partial response in nine (64.3%), stable disease in one (7.1%), and progressive disease in two (14.3%). The median progression-free survival (PFS) for all 14 patients was 15.3 months, and the five-year PFS rate was 35.7%. The five-year PFS rates in patients treated with alectinib and crizotinib were 75.0% and 20.0%, respectively. The median overall survival (OS) for all 14 patients was 36.8 months, and the five-year OS rate was 42.9%. The five-year OS rates in patients treated with alectinib and crizotinib were 75.0% and 30.0%, respectively. Conclusions: ALK inhibitors showed favorable long-term clinical outcomes in patients with ALK inhibitor-naïve ALK-positive advanced NSCLC, especially in patients treated with alectinib.

scholarly journals Immune-Related Adverse Events Are Associated With Clinical Benefit in Patients With Non-Small-Cell Lung Cancer Treated With Immunotherapy Plus Chemotherapy: A Retrospective Study

2021 ◽  
Vol 11 ◽  
Author(s):  
Kenji Morimoto ◽  
Tadaaki Yamada ◽  
Chieko Takumi ◽  
Yuri Ogura ◽  
Takayuki Takeda ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Confidence Interval ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Hazard Ratio ◽  
Small Cell Lung

BackgroundThe immunotherapy plus chemotherapy combination is one of the most promising treatments in advanced non-small-cell lung cancer (NSCLC). Immunotherapy often causes immune-related adverse events (irAEs), which have been reported to be associated with the good clinical outcomes. However, the effects of immunotherapy plus chemotherapy remain unknown. In this study, we investigated the association between irAEs caused by immunotherapy plus chemotherapy and clinical efficacy in patients with advanced NSCLC.Materials and MethodsWe retrospectively analyzed the data of patients with advanced NSCLC, who received a combination of immunotherapy plus chemotherapy at six institutions in Japan between January 2019 and September 2019. We examined the effect of irAEs on various clinical outcomes.ResultsWe included 70 patients with advanced NSCLC. Patients were divided into two groups: patients with irAEs and patients without irAEs. Patients with irAEs had significantly longer progression-free survival than those without irAEs on univariate (hazard ratio 0.53, 95% confidence interval 0.30–0.93, p = 0.026) and multivariate (hazard ratio 0.53, 95% confidence interval 0.29–0.97, p = 0.041) analyses. In addition, patients with grade 1–2 irAEs (mild irAEs) had significantly longer progression-free and overall survival than those with grade 3-5 irAEs (severe irAEs) or without irAEs on univariate (398 days versus 189 days, respectively; p = 0.0061) and multivariate (not reached versus 412 days, respectively; p = 0.021) analyses.ConclusionPatients with NSCLC who experienced mild irAEs showed better response to treatment with immunotherapy plus chemotherapy than those with severe irAEs or without irAEs. Further large-scale research is warranted to confirm these findings.

scholarly journals Prognostic impact of maximum standardized uptake value (SUVmax) of the primary lesion on survival in advanced non-small-cell lung cancer: A retrospective study

2020 ◽  
Author(s):  
Xiaoling Qiu ◽  
Hongge Liang ◽  
Wei Zhong ◽  
Jing Zhao ◽  
Minjiang Chen ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Standardized Uptake Value ◽  
Lesion Size ◽  
Lung Lesion ◽  
Small Cell ◽  
Small Cell Lung ◽  
Pet Ct

Abstract Background: Positron emission tomography/computed tomography (PET/CT) has been widely recognized for diagnosing and staging lung cancer, but the prognostic value of standardized uptake value (SUV) in patients with advanced non-small-cell lung cancer (NSCLC) remains controversial. We aim to explore whether fluorodeoxyglucose uptake has prognostic significance in patients with advanced NSCLC. Methods: We performed a retrospective analysis of the data of patients with advanced NSCLC who had undergone PET/CT before systemic treatment between June 2012 and June 2016. The relationship between the SUV of the pulmonary lesion and lesion size was evaluated via Spearman’s correlation analysis. We collected patients’ clinical and pathological data. Univariate and multivariate analyses were performed to analyze the factors influencing survival.Results: Altogether, 157 patients with advanced NSCLC were included. Among these, 135 died, 13 survived, and 9 had incomplete data (median follow-up period of 69 months). SUV was correlated with lesion size and was significantly greater for tumors ≥3 cm than for tumors <3 cm (10.2±5.4 vs. 5.6±3.3, t=-6.709, p=0.000). Univariate analysis showed that survival was associated with gender, tumor size, epidermal growth factor receptor (EGFR) gene mutation, SUV of the primary lung lesion, and treatment line. Multivariate analysis showed a significant correlation between SUV of the primary lung lesion and survival. The mortality risk of patients with SUV ≤6 was 35% lower than that of patients with SUV >6 (95% CI 0.436-0.972, Wald value 4.400, p=0.036). Conclusions: The SUV of the primary lung lesion on PET/CT is significantly correlated with survival in previously untreated patients newly diagnosed with advanced NSCLC.

Gut microbiome to predict efficacy and immune-related toxicities in patients with advanced non-small cell lung cancer treated with anti-PD-1/PD-L1 antibody-based immunotherapy.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3095-3095
Author(s):  
Taiki Hakozaki ◽  
Corentin Richard ◽  
Yusuke Okuma ◽  
Lisa Derosa ◽  
Arielle Elkrief ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Clinical Data ◽  
Cell Lung Cancer ◽  
Gut Microbiome ◽  
Small Cell ◽  
Small Cell Lung ◽  
Fecal Samples ◽  
Α Diversity

3095 Background: The gut microbiome (GM) plays an important role in shaping systemic immune responses. Preclinical and clinical data suggest that GM influences anti-PD-1/PD-L1 or -CTLA-4 Antibody (Ab)-mediated anti-cancer responses. Furthermore, there is strong evidence that antibiotics (ATB) worsen clinical outcomes based on multiple retrospective and one prospective studies using immune checkpoint inhibitor (ICI). However, whether GM profiling, at baseline or post-ATB, could represent a biomarker of response in advanced non-small cell lung cancer (NSCLC) during ICI therapy remains unknown. Methods: We prospectively collected baseline (pre-ICI) fecal samples and clinical data Japanese patients (pts) with NSCLC treated with anti-PD-1/PD-L1 Abs in first or second-line therapy. We performed a 16S rRNA V3-V4 sequencing of gene amplicons of fecal microbes. Amplicon sequence variants were generated with dada2 R package. Diversity analysis was performed with phyloseq R. Differential abundance analysis was performed with both LEfSe and DESeq2 methods. Clinical endpoints were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and immune-related adverse events (irAE). Results: 70 fecal samples were analyzed. Median OS and PFS in all patients were 16.1 and 5.2 months, respectively. 16 pts (23%) were exposed to ATB 1 month prior to ICI initiation. Pts on ATB had lower α-diversity at baseline and underrepresentation of Clostridiales and Ruminococcaceae UCG 13. When analyzing ATB-free pts, lower α-diversity was observed in non-responders. In addition, Ruminococcaceae UCG 13 was enriched in patients with OS > 12 months, favorable ORR, and PFS > 6 months. Clostridiales order was also enriched in patients with OS > 12 months. Compositional GM differences were also observed between the patients who experienced clinically significant (≥grade 2) irAE; Lactobacillaceae and Raoultella were enriched in pts who had no significant irAE. Conclusions: We demonstrated the negative influence of ATB on GM composition and identified differential bacteria repertoire in pts experiencing favorable clinical outcomes or low grade irAE. Our data pave the way to the development of diagnosis tools aimed at identifying gut dysbiosis to predict resistance or irAE during ICI for NSCLC.

scholarly journals CDKN2A loss-of-function predicts immunotherapy resistance in non-small cell lung cancer

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Stanley I. Gutiontov ◽  
William Tyler Turchan ◽  
Liam F. Spurr ◽  
Sherin J. Rouhani ◽  
Carolina Soto Chervin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Advanced Nsclc ◽  
Immune Checkpoint Blockade ◽  
Small Cell ◽  
Loss Of Function ◽  
Small Cell Lung

AbstractImmune checkpoint blockade (ICB) improves outcomes in non-small cell lung cancer (NSCLC) though most patients progress. There are limited data regarding molecular predictors of progression. In particular, there is controversy regarding the role of CDKN2A loss-of-function (LOF) in ICB resistance. We analyzed 139 consecutive patients with advanced NSCLC who underwent NGS prior to ICB initiation to explore the association of CDKN2A LOF with clinical outcomes. 73% were PD-L1 positive (≥ 1%). 48% exhibited high TMB (≥ 10 mutations/megabase). CDKN2A LOF was present in 26% of patients and was associated with inferior PFS (multivariate hazard ratio [MVA-HR] 1.66, 95% CI 1.02–2.63, p = 0.041) and OS (MVA-HR 2.08, 95% CI 1.21–3.49, p = 0.0087) when compared to wild-type (WT) patients. These findings held in patients with high TMB (median OS, LOF vs. WT 10.5 vs. 22.3 months; p = 0.069) and PD-L1 ≥ 50% (median OS, LOF vs. WT 11.1 vs. 24.2 months; p = 0.020), as well as in an independent dataset. CDKN2A LOF vs. WT tumors were twice as likely to experience disease progression following ICB (46% vs. 21%; p = 0.021). CDKN2A LOF negatively impacts clinical outcomes in advanced NSCLC treated with ICB, even in high PD-L1 and high TMB tumors. This novel finding should be prospectively validated and presents a potential therapeutic target.

scholarly journals Dosimetry, Efficacy, Safety, and Cost-Effectiveness of Proton Therapy for Non-Small Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4545
Author(s):  
Bin Qiu ◽  
Yu Men ◽  
Junjie Wang ◽  
Zhouguang Hui
Keyword(s):  
Lung Cancer ◽  
Cost Effectiveness ◽  
Small Cell Lung Cancer ◽  
Clinical Outcomes ◽  
Cell Lung Cancer ◽  
Proton Therapy ◽  
Advanced Nsclc ◽  
Early Stage ◽  
Small Cell ◽  
Small Cell Lung

Non-small cell lung cancer (NSCLC) is the most common malignancy which requires radiotherapy (RT) as an important part of its multimodality treatment. With the advent of the novel irradiation technique, the clinical outcome of NSCLC patients who receive RT has been dramatically improved. The emergence of proton therapy, which allows for a sharper dose of build-up and drop-off compared to photon therapy, has potentially improved clinical outcomes of NSCLC. Dosimetry studies have indicated that proton therapy can significantly reduce the doses for normal organs, especially the lung, heart, and esophagus while maintaining similar robust target volume coverage in both early and advanced NSCLC compared with photon therapy. However, to date, most studies have been single-arm and concluded no significant changes in the efficacy for early-stage NSCLC by proton therapy over stereotactic body radiation therapy (SBRT). The results of proton therapy for advanced NSCLC in these studies were promising, with improved clinical outcomes and reduced toxicities compared with historical photon therapy data. However, these studies were also mainly single-arm and lacked a direct comparison between the two therapies. Currently, there is much emerging evidence focusing on dosimetry, efficacy, safety, and cost-effectiveness of proton therapy for NSCLC that has been published, however, a comprehensive review comparing these therapies is, to date, lacking. Thus, this review focuses on these aspects of proton therapy for NSCLC.

The comparison of 18F-alfatide PET/CT and 18F-FDG PET/CT in predicting chemoradiotherapy sensitivity in patients with advanced non-small cell lung cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e20558-e20558
Author(s):  
Xiaohui Luan ◽  
Yong Huang ◽  
Ning Liu ◽  
Song Gao ◽  
Jinsong Zheng ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Logistic Regression ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Fdg Pet ◽  
Advanced Nsclc ◽  
Small Cell ◽  
Small Cell Lung ◽  
Pet Ct ◽  
Fdg Pet Ct

e20558 Background: Both 18F-alfatide positron emission tomography/computed tomography(PET/CT) and 18F-fluorodeoxyglucose (18F-FDG) PET/CT were potential in predicting thearapy sensitivity, in this study,we recruited patients with advanced NSCLC to detect and compare the potential predictive vaue of them on the CRT sensitivity of patients with advanced non-small cell lung cancer (NSCLC). Methods: According to the design of Natural Science Foundation ofChina (NSFC) 81372413, twenty-four patients with advanced NSCLC accepted 18F-alfatide PET/CT before radiotherapy (T1), another thirty-nine patients underwent 18F-FDG PET/CT at both T1 and during CRT (40Gy of radiotherapy, T2). Logistic regression analyse was used to evaluate the correlations between PET parameters and CRT sensitivity providing an odds ratio (OR), 95% confidence interval (CI) and p value. Propensity score matching (PSM) approach was used to control confounding. Results: Logistic regression analyse showed that Karnofsky Performance Status (KPS) score was correlative with CRT sensitivity. After PSM, controlling KPS scores, twenty-four pairs of patients were matched. The results showed that SUVmax obtained from baseline 18F-alfatide PET/CT was associated with CRT sensitivity in both univariate and multivariable logistic regression analysis (OR: 0.532, 95% CI: 0.305–0.927, p = 0.026; OR:0.376, 95% CI: 0.165-0.860, p = 0.021), but the baseline 18F-FDG PET/CT was not. Univariate analyses showed that the percent change in MTV of 18F-FDG PET/CT between T1 and T2 was correlative with CRTsensitivity (OR: 1.039, 95% CI: 1.003-1.077, p = 0.036). When patients’ KPS score was considered simultaneously, it was still related to CRT sensitivity (OR:1.038, 95% CI: 1.001-1.077, p = 0.045). Conclusions: 18F-alfatidePET/CT may be better than 18F-FDG PET/CT in predicting CRT sensitivity, and 18F-FDG PET/CT is potential in monitoring the tumor response to CRT in patients with advanced NSCLC.

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