scholarly journals The association between gut microbiome affecting concomitant medication and the effectiveness of immunotherapy in patients with stage IV NSCLC

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
M. V. Verschueren ◽  
C. M. Cramer - van der Welle ◽  
M. Tonn ◽  
F. M. N. H. Schramel ◽  
B. J. M. Peters ◽  
...  
Keyword(s):  
Gut Microbiome ◽  
Observational Studies ◽  
Cox Regression ◽  
Stage Iv ◽  
Effect Modification ◽  
Small Cell ◽  
Regression Analyses ◽  
Small Cell Lung ◽  
Interaction Term ◽  
Nsclc Patients

AbstractSeveral observational studies suggested that gut microbiome-affecting-medication impairs the effectiveness of immunotherapy in patients with metastatic non-small-cell lung cancer (NSCLC). We postulated that if the effectiveness of immunotherapy is affected by drug-related changes of the microbiome, a stronger association between the use of co-medication and overall survival (OS) will be observed in patients treated with immunotherapy as compared to patients treated with chemotherapy. In a retrospective matched cohort study, immunotherapy patients were matched (1:1) to patients treated with chemotherapy in the pre immunotherapy era. The association between the use of antibiotics, opioids, proton pump inhibitors, metformin and other antidiabetics on OS was assessed with multivariable cox-regression analyses. Interaction tests were applied to investigate whether the association differs between patients treated with immuno- or chemotherapy. A total of 442 patients were studied. The use of antibiotics was associated with worse OS (adjusted Hazard Ratio (aHR) 1.39, p = 0.02) independent of the type of therapy (chemotherapy or immunotherapy). The use of opioids was also associated with worse OS (aHR 1.33, p = 0.01). The other drugs studied showed no association with OS. Interaction term testing showed no effect modification by immuno- or chemotherapy for the association of antibiotics and opioids with OS. The use of antibiotics and opioids is similarly associated with worse outcomes in both chemotherapy and immunotherapy treated NSCLC patients. This suggests that the association is likely to be a consequence of confounding rather than disturbing the composition of the microbiome.

The Association Between Gut Microbiome Affecting Concomitant Medication and The Related Effectiveness of Immunotherapy in Patients With Stage IV NSCLC

2021 ◽  
Author(s):  
M. V. Verschueren ◽  
C.M. Cramer- van der Welle ◽  
M. Tonn ◽  
F. M.N.H. Schramel ◽  
B. J.M. Peters ◽  
...  
Keyword(s):  
Concomitant Medication ◽  
Cox Regression ◽  
Stage Iv ◽  
Effect Modification ◽  
Small Cell ◽  
Regression Analyses ◽  
Small Cell Lung ◽  
Confounding By Indication ◽  
Interaction Term ◽  
Nsclc Patients

Abstract Objectives This historically matched cohort study investigated the influence of microbiome-affecting-medication on the effectiveness of immunotherapy in patients with stage IV non-small-cell lung cancer (NSCLC). We postulated that if the effectiveness of immunotherapy is mediated by drug-related changes of the microbiome, a stronger association between the use of co-medication and overall survival (OS) will be observed in patients treated with immunotherapy as compared to patients treated with chemotherapy. Methods Immunotherapy patients were matched (1:1) to patients treated with chemotherapy in the pre immunotherapy era. The association between the use of antibiotics, opioids, proton pump inhibitors, metformin and other antidiabetics on OS was assessed with multivariable cox-regression analyses. Interaction tests were applied to investigate whether the association differs between patients treated with immuno- or chemotherapy. Results A total of 442 patients were studied. The use of antibiotics was associated with worse OS (adjusted Hazard Ratio (aHR) 1.39, p = 0.02) independent of the type of therapy (chemotherapy or immunotherapy). The use of opioids was also associated with worse OS (aHR 1.33, p = 0.01). The other drugs studied showed no association with OS. Interaction term testing showed no effect modification by immuno- or chemotherapy for the association of antibiotics and opioids with OS. Conclusion The use of antibiotics and opioids is similarly associated with worse outcomes in both chemotherapy and immunotherapy treated NSCLC patients. This suggests that the association is likely to be a consequence of confounding by indication rather than disturbing the composition of the microbiome.

scholarly journals Risk factors for radiation-induced lung injury in patients with advanced non-small cell lung cancer: implication for treatment strategies

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Sha Sha ◽  
Jigang Dong ◽  
Maoyu Wang ◽  
Ziyu Chen ◽  
Peng Gao
Keyword(s):  
Risk Factors ◽  
Lung Cancer ◽  
Logistic Regression ◽  
Concurrent Chemotherapy ◽  
Small Cell ◽  
Regression Analyses ◽  
Small Cell Lung ◽  
Radiation Induced ◽  
Radiotherapy Dose ◽  
Nsclc Patients

Abstract Background The radiation-induced lung injury (RILI) in patients with advanced non-small cell lung cancer (NSCLS) is very common in clinical settings; we aimed to evaluate the risk factors of RILI in NSCLS patients, to provide insights into the treatment of NSCLS. Methods NSCLC patients undergoing three-dimensional conformal radiotherapy (3D-CRT) in our hospital from June 1, 2018, to June 30, 2020, were included. The characteristics and treatments of RILI and non-RILI patients were analyzed. Logistic regression analyses were conducted to assess the risk factors of RILI in patients with NSCLC. Results A total of 126 NSCLC patients were included; the incidence of RILI in NSCLC patients was 35.71%. There were significant differences in diabetes, smoke, chronic obstructive pulmonary disease (COPD), concurrent chemotherapy, radiotherapy dose, and planning target volume (PTV) between the RILI group and the non-RILI group (all P < 0.05). Logistic regression analyses indicated that diabetes (OR 3.076, 95%CI 1.442~5.304), smoke (OR 2.745, 95%CI 1.288~4.613), COPD (OR 3.949, 95%CI 1.067~5.733), concurrent chemotherapy (OR 2.072, 95%CI 1.121~3.498), radiotherapy dose ≥ 60 Gy (OR 3.841, 95%CI 1.932~5.362), and PTV ≥ 396 (OR 1.247, 95%CI 1.107~1.746) were the independent risk factors of RILI in patients with NSCLC (all P < 0.05). Conclusions RILI is commonly seen in NSCLS patients; early targeted measures are warranted for patients with those risk factors; future studies with larger sample sizes and different areas are needed to further elucidate the influencing factors of RILI in the treatment of NSCLS.

scholarly journals Therapeutic and Prognostic Implications of Immune-Related Adverse Events in Advanced Non-Small-Cell Lung Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Lea Daniello ◽  
Mariam Elshiaty ◽  
Farastuk Bozorgmehr ◽  
Jonas Kuon ◽  
Daniel Kazdal ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Palliative Radiotherapy ◽  
Small Cell ◽  
Small Cell Lung ◽  
Treatment Type ◽  
Nsclc Patients

IntroductionPD-(L)1 inhibitors have improved prognosis of non-small-cell lung cancer (NSCLC), but can also cause immune-related adverse events (irAEs) that complicate management.MethodsWe analyzed NSCLC patients receiving PD-(L)1 inhibitors from 2012 to 2020 in a German academic center.ResultsIrAE showed comparable frequencies in stage IV (198/894 or 22%) vs. III (14/45 or 31%, p = 0.15), after anti-PD-(L)1 monotherapy vs. chemoimmunotherapy (139/483 vs. 58/213, p = 0.75), and across treatment lines. In stage IV, irAE occurred after 3.1 months in median, affected multiple organs (median 2) in 27/894 patients and were associated with PD-L1 positivity (25 vs. 14%, p = 0.003), lower neutrophil-to-lymphocyte ratios (29 vs. 17%, p &lt; 0.001 for NLR dichotomized at 5), better ECOG status (26 vs. 18% for 0 vs. 1, p = 0.004), but not related to age, sex, smoking and palliative radiotherapy. Two hundred thirty two irAEs occurred mostly in endocrine glands (4.9%), lungs (4.4%), the musculoskeletal system (4.2%), colon (4.1%), liver (3.7%), and skin (2.6%), while pneumonitis was most frequent with durvalumab following definitive chemoradiation (16% or 7/45, p &lt; 0.01). IrAE severity was grade 1 in 11%, 2 in 41%, 3 in 36%, and 4 in 11% events, while two were lethal (&lt;1%, myocarditis and pneumonitis). Therapy was suspended in 72%, while steroids were initiated in 66% and complemented by other immunosuppressants in 6%, with longest treatment duration for rheumatic events (mean &gt;3 months), and average cumulative prednisone doses &gt;700 mg for all organs, except for skin. Patients developing irAE had longer progression-free (PFS) and overall survival (OS) in multivariable 12/14-week landmark analyses including ECOG status, treatment line, treatment type, PD-L1 TPS, and NLR (median PFS 17 vs. 10 months, HR = 0.68, p = 0.009; median OS 37 vs. 15 months, HR = 0.40, p &lt; 0.001), regardless of grade. OS was longest with skin (95% at 2 years) and shortest with pneumonitis, hepatitis, neurologic, and cardiologic irAE (38, 37, 28, and 0% at 2 years, p &lt; 0.001).ConclusionsApproximately one-fourth of immunotherapy-treated NSCLC patients develop irAEs, most of which necessitate treatment suspension and steroids. Despite more frequent occurrence with PD-L1 positive tumors, lower NLR, and better ECOG PS, irAEs are independently associated with longer survival, especially when affecting the skin. Lethality is below 1%.

scholarly journals Serum miR-1228-3p and miR-181a-5p as Noninvasive Biomarkers for Non-Small Cell Lung Cancer Diagnosis and Prognosis

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Wei-Xiao Xue ◽  
Meng-Yu Zhang ◽  
Rui Li ◽  
Xiao Liu ◽  
Yun-Hong Yin ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Roc Analysis ◽  
Cox Regression ◽  
Small Cell ◽  
Healthy Controls ◽  
Small Cell Lung ◽  
Cox Regression Analysis ◽  
Diagnosis And Prognosis ◽  
Noninvasive Biomarkers ◽  
Nsclc Patients

Background. Lung cancer is the leading cause of cancer-related mortality worldwide, and non-small cell lung cancer (NSCLC) accounts for over 80% of all lung cancers. Serum microRNAs (miRNAs), due to their high stability, have the potential to become valuable noninvasive biomarkers. This present study was aimed to identify the serum miRNAs expression signatures for the diagnosis and prognosis of NSCLC using bioinformatics analysis. Methods. A total of 12 miRNAs profiling studies have been identified in Pubmed, Gene Expression Omnibus (GEO), and ArreyExpress databases. Differentially expressed miRNAs (DEmiRNAs) were analyzed according to GEO2R online tool and RRA method from R. Then, prediction of DEmiRNAs’ target genes from TargetScan, PicTar, miRDB, Tarbase, and miRanda database. Furthermore, we using reverse transcription– quantitative polymerase chain reaction (RT-qPCR) to evaluate the expression levels of DEmiRNAs in serum samples obtained from NSCLC patients and healthy controls. Subsequently, the clinical significance of the tested miRNAs was determined using receiver operating characteristic (ROC) analysis and Cox regression analysis. Results. A total of 27 DEmiRNAs were identified and 5 of them (miR-1228-3p, miR-1228-5p, miR-133a-3p, miR-1273f, miR-545-3p) were significantly up-regulated and 4 of them (miR-181a-5p, miR-266-5p, miR-361-5p, miR-130a-3p) were significantly down-regulated in NSCLC patients compared with healthy controls. RT-qPCR validated that miR-1228-3p (P =0.006) and miR-181a-5p (P =0.030) were significantly differentially expressed in the serum of NSCLC patients and healthy controls. ROC analysis on miR-1228-3p and miR-181a-5p revealed the area under the curve (AUC) of 0.685 (95% confidence interval [CI], 0.563–0.806; P =0.006) and 0.647 (95% CI, 0.506–0.758; P =0.049). ROC analysis on miR-1228-3p combined miR-181a-5p revealed the AUC of 0.711 (95% CI, 0.593–0.828; P =0.002). Multivariate Cox regression analysis demonstrated that the high serum miR-1228-3p level was an independent factor for the poor prognosis of NSCLC patients. Conclusions. Serum miR-1228-3p and miR-181a-5p are potential noninvasive biomarkers for the diagnosis and prognosis of NSCLC patients.

Randomized Trial Comparing Cisplatin, Gemcitabine, and Vinorelbine With Either Cisplatin and Gemcitabine or Cisplatin and Vinorelbine in Advanced Non–Small-Cell Lung Cancer: Interim Analysis of a Phase III Trial of the Southern Italy Cooperative Oncology Group

2000 ◽  
Vol 18 (7) ◽  
pp. 1451-1457 ◽  
Author(s):  
Pasquale Comella ◽  
Giuseppe Frasci ◽  
Nicola Panza ◽  
Luigi Manzione ◽  
Giuseppe De Cataldis ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Interim Analysis ◽  
Stage Iv ◽  
Small Cell ◽  
Phase Iii ◽  
Oncology Group ◽  
Small Cell Lung ◽  
Nsclc Patients

PURPOSE: In our previous phase II study, the cisplatin, gemcitabine, and vinorelbine (PGV) regimen produced a median survival time (MST) of approximately 1 year in advanced non–small-cell lung cancer (NSCLC) patients. The present study was aimed at comparing the MST of patients treated with this triplet regimen with the MSTs of patients receiving cisplatin and vinorelbine (PV) or cisplatin and gemcitabine (PG). PATIENTS AND METHODS: From April 1997, patients with locally advanced or metastatic NSCLC, an age of ≤ 70 years, and an Eastern Cooperative Oncology Group performance status ≤ 1 were randomized to receive one of the following regimens: cisplatin 50 mg/m2, gemcitabine 1,000 mg/m2, and vinorelbine 25 mg/m2 on days 1 and 8 every 3 weeks (arm A); cisplatin 100 mg/m2 on day 1 and gemcitabine 1,000 mg/m2 on days 1, 8, and 15 every 4 weeks (arm B); or cisplatin 120 mg/m2 on days 1 and 29 and vinorelbine 30 mg/m2/wk (arm C). According to the two-stage design for phase III trials, an interim analysis was planned when the first 60 patients per arm were assessable for survival. RESULTS: The survival data of 180 NSCLC patients (stage IIIB, 76 patients; stage IV, 104 patients) were analyzed in April 1999. Overall, 128 patients had died (PGV, n = 33; PG, n = 42; and PV, n = 53). The MST of patients in the PGV, PG, and PV arms was 51, 42, and 35 weeks, respectively, and the corresponding 1-year projected survival rates were 45%, 40%, and 34%, respectively. When only patients with stage IV disease were considered, an even stronger difference was seen between PGV (MST = 47 weeks) and both PG (34 weeks) and PV (27 weeks). At multivariate Cox analysis, the estimate hazard of death for patients receiving PGV compared with those receiving PV was 0.35 (95% confidence interval, 0.16 to 0.77; P < .01). The response rates were 47% in the PGV arm, 30% in the PG arm, 25% in the PV arm. Both hematologic and nonhematologic toxicities were not substantially worse in patients who received the PGV regimen. CONCLUSION: The PGV regimen is associated with a substantial survival gain (MST > 3 months longer) when compared with the PV combination. Because this difference in survival met one of the early stopping rules, the accrual in the PV arm has been stopped (null hypothesis rejected). Enrollment still continues in the PGV and PG arm to ascertain whether the PGV regimen can also produce a significantly longer survival than that obtained with the PG regimen.

Examining the use of PET scans in the diagnosis and management of non-small cell lung cancer patients.

2014 ◽  
Vol 32 (30_suppl) ◽  
pp. 311-311
Author(s):  
Cheryl Louzado ◽  
Kristen DeCaria ◽  
Jose Hernandez ◽  
Rami Rahal ◽  
Jin Niu ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Stage Iv ◽  
Small Cell ◽  
Pet Scan ◽  
Small Cell Lung ◽  
Diagnosis And Management ◽  
Nsclc Patients ◽  
Pet Scans

311 Background: PET Scans are increasingly used in the diagnosis and management of non-small cell lung cancer (NSCLC) patients. However, uptake of PET at provincial level is not well studied. This project, led by the Canadian Partnership Against Cancer, established processes and indicators to describe utilization of PET in patients with NSCLC. These indicators support the monitoring of uptake and highlight areas for quality improvement strategies at the national and provincial level. Methods: Cases of NSCLC, diagnosed in the study period of 2009-2011, were identified from cancer registries and linked to PET utilization data. PET scans were identified as indicated for diagnosis/staging or treatment response, based on the timing of scans relative to diagnosis and treatment dates. Scans conducted three months prior to and up to four months post-diagnosis but before start of treatment (surgery or radiation) were identified as diagnosis/staging. Scans conducted after the start of treatment to ten weeks post-treatment were identified as management and follow-up of treatment. Results: A total of 27,984 cases of NSCLC were identified. Preliminary analysis revealed that 8,947 (32.0%) of NSCLC patients had at least one PET scan. Some variation was seen in age, with those 18 to 69 years more likely to receive a scan than those 70 years and older. PET scan use was higher among stages I and II (52.3% to 50.6%) compared to stage IV (17.98%). A majority of PET scans were performed for diagnosing/staging NSCLC (91.1%). PET scans for diagnosis/staging were highest for patients with stage I (36.7%) followed by stage IV (24.6%). Conclusions: This study provided information on the current use of PET technology across Canada, allowing for identification of opportunities for increasing evidence-based use while decreasing extra-evidential use, and forming a baseline for future monitoring as evidence evolves.

Time from stereotactic body radiotherapy to immunotherapy as a predictor for outcome in metastatic non small cell lung cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 9024-9024
Author(s):  
Rodney E Wegner ◽  
Stephen Abel ◽  
Shaakir Hasan ◽  
Richard White ◽  
Gene Grant Finley ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Overall Survival ◽  
Small Cell Lung Cancer ◽  
Median Survival ◽  
Stereotactic Body Radiotherapy ◽  
Cox Regression ◽  
Stage Iv ◽  
Small Cell ◽  
Small Cell Lung ◽  
Kaplan Meier

9024 Background: Immunotherapy has changed the face of treatment for stage IV non small cell lung cancer (NSCLC), quickly becoming the standard of care. The appropriate timing of immunotherapy in the setting of other ablative therapies, namely stereotactic radiosurgery (SRS) and stereotactic body radiotherapy (SBRT), remains to be determined. We sought to use the National Cancer Database to examine trends in immunotherapy use as well as timing as it relates to SBRT/SRS in stage IV NSCLC patients. Methods: We queried the NCDB for patients with Stage IV NSCLC diagnosed between 2004-2015 that were treated with SRS or SBRT techniques (to any site) and had at least three months of follow up. Multivariable logistic regression was used to identify predictors of immunotherapy use. Receiver operator curve analysis was used to identify the optimal timepoint between SBRT and immunotherapy correlating with overall survival. Kaplan-meier curves were generated to determine overall survival. Multivariable cox regression was used to determine factors predictive of survival. A propensity score was generated and incorporated into Kaplan-meier and cox regressions to account for indication bias. Results: We identified 13,862 patients meeting the above eligibility criteria, 371 being treated with immunotherapy. The vast majority (75%) had chemotherapy as well. Patients with adenocarcinoma, treatment with chemotherapy, and more recent year of treatment were more likely to receive immunotherapy. Univariable Kaplan-meier analysis showed improved median survival with immunotherapy, 17 months vs. 13 months, p < 0.0001. On multivariable propensity-adjusted cox regression significant predictors for improved overall survival were younger age, lower comorbidity score, lower grade, private insurance, and female gender. Using a cutoff of 21 days after start of SBRT, patients treated thereafter were more likely to survive longer, median survival of 19 months vs 15 months, p = 0.0335. Conclusions: Immunotherapy use in Stage IV NSCLC after SBRT has increased over time, mostly in patients with adenocarcinoma and in the setting of chemotherapy. In this analysis, outcomes were improved when immunotherapy was given at least three weeks after start of SBRT.

Comparison of characteristics and outcomes among veterans receiving first-line immunotherapy versus chemotherapy for stage IV non-small cell lung cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e19295-e19295
Author(s):  
Christina D Williams ◽  
Lin Gu ◽  
Vishal Vashistha ◽  
Ashlyn Press ◽  
Michael J. Kelley
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Clinical Characteristics ◽  
Cox Regression ◽  
Stage Iv ◽  
Small Cell ◽  
Small Cell Lung ◽  
First Line ◽  
Outpatient Visits

e19295 Background: Immunotherapy (IO) has revolutionized the treatment paradigm for patients with advanced non-small cell lung cancer (NSCLC). Study objectives were to evaluate utilization of IO as first-line (1L) therapy and compare clinical characteristics between patients receiving IO and those receiving CT in 1L setting. Methods: Using the U.S. Department of Veterans Affairs corporate data warehouse, patients with stage IV NSCLC diagnosed 2012-2017 and initiated non-targeted systemic therapy within 120 days of diagnosis were selected. Unadjusted descriptive statistics were used to compare patient characteristics, inpatient and outpatient clinic visits, and prevalence of select adverse events (AE) between patients receiving IO monotherapy and CT. Kaplan-Meier and Cox regression approaches with and without propensity score matching (PSM) were used for overall survival (OS) analyses. OS was calculated from treatment initiation date to death or end of study period in June 2019. Results: 4609 patients were included in the analysis: 3.4% (n = 156) received IO monotherapy, 96% (n = 4426) received CT, and 0.6% (n = 27) received IO+CT (IO+CT not included in analysis). IO patients were older than CT patients (median age 69 vs. 66 years, p < 0.0001) and more frequently resided in the Midwest and West regions whereas CT patients were more likely to live in the Northeast and South (p = 0.0024). There were no significant differences in IO and CT by other demographic and clinical characteristics. Estimated median OS was 7.5 months (95% CI 7.2-7.7) for CT and 7.9 months (95% CI 5.3-12.6) for IO patients. The unadjusted HR for IO compared to CT patients was 0.81 (95% CI 0.67-0.98). With 1:4 PSM (144 and 559 patients matched in the IO and CT groups, respectively), the HR was 0.75 (95% CI 0.60-0.93). The mean number of outpatient visits for IO and CT patients were 47 and 36, respectively (p = 0.003). No difference in number of hospitalizations or length of hospital stays between the two groups was observed. Common AEs in the IO group were dyspnea (58%), colitis/enterocolitis (42%), and anemia (30%). Common AEs among CT patients were colitis/enterocolitis (36%), anemia (32%), and nausea/vomiting (31%). Conclusions: In a real-world 1L setting among veterans with NSCLC, improvement in OS was observed among patients receiving IO monotherapy compared to those receiving CT, and IO patients had a greater number of outpatient visits. Continued assessment of treatment patterns and impact of IO are needed as the use of IO continues to expand.

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