Concurrent TP53 mutation adversely impact the efficacy of crizotinib in ROS1-rearranged lung cancer patients.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e20535-e20535
Author(s):  
Lin Gen ◽  
Huamin Xu ◽  
Jun Zhao ◽  
Jinliang Kong ◽  
Xinghao Ai ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Tp53 Mutation ◽  
Rank Test ◽  
Fresh Tissue ◽  
Lung Cancer Patients ◽  
Cns Metastasis ◽  
Clinical Records ◽  
Mutation Profiling

e20535 Background: ROS1 tyrosine kinase inhibitors (TKIs) are now standard of care for patients with advanced ROS1-rearranged NSCLC. But factors that may affect the efficacy of ROS1 TKIs remain to be explored. Methods: We conducted a retrospective multicenter study of lung cancer patients with ROS1 rearrangements. Treatment and survival follow-up was done and clinical records were reviewed. PFS distribution was analyzed by Kaplan-Meier method with log-rank test. Results: In total, we included 94 lung cancer patients with ROS1 fusion genes profiled by next-generation sequencing from May 2016 to September 2018. Fifty of them were female. The median diagnosis age was 54 (25-83). The most common histologic type was adenocarcinoma, which was confirmed in 75 of 78 patients with available pathological results. The most common fusion partners were CD74, EZR, SDC4 and SLC34A2 identified in 42, 19, 12 and 8 patients respectively. Concurrent actionable mutations were uncommon for ROS1 fusion-positive patients. The most frequent concomitant mutated gene was TP53, which was detected in 33% of all the patients. After excluding 29 patients who were lost to follow-up at the very start, the median follow-up time was 8.5 (0-28) months from the moment when mutation profiling was performed. Thirty-nine patients received treatment with crizotinib, among whom 27 were treatment-naïve patients. The median PFS of the 39 patients with crizotinib was not reached yet. Patients with baseline CNS metastasis tend to have shorter PFS compared to patients without (median, 12 vs NR, p = 0.0073). Besides, concurrent TP53 mutations were correlated with worse PFS (median, both NR, p = 0.0417). Mutation profiles of 10 patients were derived from ctDNA testing. No difference was found in PFS between these 10 patients with others whose genomic profiles were based on fresh tissue or FFPE specimens, suggesting that plasma ctDNA serves as good specimen source for mutation profiling to monitor clinical treatment. Conclusions: Concurrent TP53 mutation and presence of CNS metastasis are associated with decreased PFS of ROS1-positive patients treated with crizotinib.

A New Multiparametric Classification in Lung Cancer Patients - S.M.I.G.

1983 ◽  
Vol 69 (5) ◽  
pp. 437-443 ◽  
Author(s):  
Claudio Modini ◽  
Mario Albertucci ◽  
Franco Cicconetti ◽  
Donatella Tirindelli Danesi ◽  
Renzo Cristiani ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Growth Rate ◽  
Mortality Rate ◽  
Cancer Patients ◽  
Cell Type ◽  
Tnm System ◽  
Lung Cancer Patients ◽  
The Difference

The classification of bronchogenic carcinoma as a function of the prognosis is still an open field. The evaluation of stage, by use of the TNM system, and histologic cell type is not sufficient to guarantee a correct prognosis. The growth rate of the neoplasm is another important parameter. We propose a classification that takes into account the stage (S), histologic cell type (M), immune status (I) and the growth rate of the primary tumor (G): S.M.I.G. We studied 90 lung cancer patients according to the S.M.I.G. classification and we observed that their prognoses were directly correlated with their S.M.I.G. scores (the higher the score, the higher the 10-month mortality rate). The mortality rates within the first 10 months of follow-up were respectively 0%, 0%, 36.36%, 68%, 90.9% for the 5 groups obtained by S.M.I.G. The difference is statistically significant (P < 0.0075) and there is a linear correlation between the mortality rate and the score assigned to each group (R = 0.943; P < 0.05). The S.M.I.G. classification can predict the prognosis more efficiently than the usual classification (TNM) and histological cell type.

scholarly journals Baseline Plasma EGFR Circulating Tumour DNA Levels in a Pilot Cohort of EGFR-Mutant Limited-Stage Lung Adenocarcinoma Patients Undergoing Radical Lung Radiotherapy

2020 ◽  
Vol 13 (2) ◽  
pp. 896-903
Author(s):  
Brendan Seng Hup Chia ◽  
Wen Long Nei ◽  
Sabanayagam Charumathi ◽  
Kam Weng Fong ◽  
Min-Han Tan
Keyword(s):  
Lung Cancer ◽  
Lung Adenocarcinoma ◽  
Cancer Patients ◽  
Early Stage ◽  
Early Stage Disease ◽  
Lung Cancer Patients ◽  
Limited Stage ◽  
Potential Biomarker ◽  
Egfr Mutant

The use of circulating cell-free tumour DNA (ctDNA) is established in metastatic lung adenocarcinoma to detect and monitor sensitising EGFR mutations. In early-stage disease, there is very little data supporting its role as a potential biomarker. We report on a prospective cohort of 9 limited-stage EGFR mutant lung cancer patients who were treated with radical radiotherapy. We looked at baseline plasma EGFR ctDNA and noted the detection rates to be higher in locally advanced disease. At a median follow-up of 13.5 months, an association between a detectable pre-radiotherapy plasma EGFR ctDNA and early tumour relapse (155 days vs. NR, p = 0.004) was noted. One patient with persistent plasma EGFR ctDNA predated radiological progression. The role of ctDNA in early-stage lung cancer is developing. Plasma EGFR ctDNA could be a useful biomarker in lung cancer patients undergoing radical treatments for staging, prognostication, and follow-up. These preliminary findings should be explored in larger studies.

Clinical significance of cytokines levels in exhaled breath condensate (EBC) and serum of lung cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e22202-e22202
Author(s):  
Georgia Lamprodimou ◽  
Athanasios Athanasiadis ◽  
Theodora Kerenidi ◽  
Dimitrios Doufexis ◽  
Martha Lada ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Patients ◽  
Smoking Status ◽  
Prognostic Significance ◽  
Stage Iv ◽  
Serum Levels ◽  
Rank Test ◽  
Exhaled Breath ◽  
Lower Serum ◽  
Lung Cancer Patients

e22202 Background: Cytokines are known to play an important role in carcinogenesis.The aim of this study is to measure pre-treatment concentrations of cytokines IL6, IL10, IL1β and IL8, in EBC and serum of lung cancer patients and to assess any possible association with clinicopathological variables and survival. Methods: From February 2010 to May 2011 we enrolled 73 patients with previously untreated lung cancer, 67 males and 6 females, age 67.7±9.5 years, 46 smokers and 27 ex-smokers, and 30 healthy individuals as controls. Sixty-one patients had NSCLC and 12 SCLC (5 stage I, 3 stage II, 19 stage III and 46 stage IV). EBC was collected using the Ecoscreen device (Viasys, Germany). Serum and EBC levels of cytokines were analyzed by commercially available enzyme-immunosorbent assay kits (ELISA). Results: All cytokines but IL8 were detectable in both materials. IL8 was not detected in EBC. All cytokines were significantly increased in patients with lung cancer in comparison to controls (IL6: serum P<0.0001, EBC P=0.001; IL10: serum P= 0.006, EBC P=0.037; IL1β: serum P= 0.032, EBC P=0.005; IL8 serum P=0.001). Moreover, a statistically significant correlation was found between IL10 levels in EBC and serum (P=0.001, Rho=0.334). In EBC, higher levels of IL6 were found in patients with T3-T4 disease than in those with T1-T2 [4.27 pg/ml (2.46-5.99) vs 3.12 pg/ml (1.35-5.03), P=0.036]. Furthermore, smokers had higher serum levels of IL6 compared to ex-smokers [10.19 pg/ml (4.92-17.38) vs 4.46 pg/ml (1.88-11.53), P=0.009]. Finally, lower serum levels of IL6 < median value (9.55pg/ml) were associated with improved survival (median overall survival 338 days vs 237 days Log Rank test, P= 0.046). Conclusions: Elevated levels of measured cytokines were found in both EBC and serum of lung cancer patients. Particularly, IL6 levels were related to T-stage and smoking status, while lower serum levels of IL6 with survival. These findings suggest that cytokines should be further studied in order to evaluate their diagnostic and prognostic significance. EBC could provide a simple, noninvasive and economic method for the monitoring of biomarkers in patients with lung cancer.

Overall survival in patients with lung cancer using a web-application-guided follow-up compared to standard modalities: Results of phase III randomized trial.

2016 ◽  
Vol 34 (18_suppl) ◽  
pp. LBA9006-LBA9006 ◽  
Author(s):  
Fabrice Denis ◽  
Claire Lethrosne ◽  
Nicolas Pourel ◽  
Olivier Molinier ◽  
Yoann Pointreau ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
High Risk ◽  
Supportive Care ◽  
Cancer Patients ◽  
Web Application ◽  
Phase Iii ◽  
P Value ◽  
Lung Cancer Patients

LBA9006 Background: We developed a web-application for an early detection of symptomatic relapse, complications and early supportive care in high-risk lung cancer patients between visits. A dynamical analysis of the weekly self-reported symptoms automatically triggered physician visit. Methods: We performed a national multi-institutional phase 3 prospective randomized study to compare web-application follow-up (experimental arm) for which patient’s self-scored symptoms that were weekly sent (between planned visits) to the oncologist and a clinical routine assessment with a CT-scan (every 3-6 months or at investigator’s discretion - standard arm). High risk lung cancer patients without progression and with a 0-2 performance status (PS) after an initial treatment were included. Maintenance chemotherapy or TKI therapy were allowed. In the experimental arm, an email alert was sent to the oncologist when some predefined clinical criteria were fulfilled: an imaging was then quickly prescribed. Early supportive cares were provided if adequate. The primary endpoint was to detect an improvement of 12% in 9 months survival in favor of the experimental arm (α = 5%, β = 20%, unilateral test). The boundary for declaring superiority with respect to overall survival at the pre-planned interim analysis was a p-value of less than 0.006. The PS at relapse, the quality of life (QOL) and cost-effectiveness were also investigated. Results: 121 patients were included in the intent-to-test survival analysis (90% were stage III/IV, median age: 65 y): 60 (61) in the experimental (standard) arms with equivalent baseline characteristics. Median follow-up was 9 months. Median overall survival in months was 19 (11.8), p=0.0014 (n  =  121; HR  =  0.33; 95 % CI, 0.16-0.67) and the PS at the first relapse was 0-1 for 81.5% (35.3%) of the patients (p<0.001) in the experimental (standard) arm. Conclusions: This trial shows a significant survival improvement using Web-application-guided follow-up that allowed better PS at relapse, earlier supportive care and reduction of routine imaging. QOL and cost analysis results will be presented during the meeting. Clinical trial information: NCT02361099.

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