Immunotherapy Use in Patients With Lung Cancer and Comorbidities.
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ABSTRACT:
SUBMITTER: von Itzstein MS
PROVIDER: S-EPMC7735252 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Veterans with locoregional non-small cell lung cancer (NSCLC) may benefit from adjuvant chemotherapy. However, comorbidities and other factors may impact the harms and benefits of this treatment. Here, we identified the optimal indications for adjuvant chemotherapy in Veterans with NSCLC, chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), and/or coronary artery disease (CAD). We used data from randomized controlled trials (RCTs) and Veterans Administration (VA) databases to enhance a simulation model. Then, we conducted in-silico RCTs comparing adjuvant chemotherapy vs observation among Veterans with stage II-IIIA NSCLC. Among Veterans without COPD or CKD, adjuvant chemotherapy was the optimal strategy regardless of the presence or absence of CAD except for patients >70 years with squamous cell carcinoma. Conversely, most veterans without COPD but with CKD were optimally managed with observation. Veterans with COPD but without CKD, benefited from adjuvant chemotherapy if they were ≤70 years with stage II-IIIA adenocarcinoma or <60 years with stage II-IIIA squamous cell carcinoma. Adjuvant chemotherapy was only beneficial for Veterans with both COPD and CKD among stage II-IIIA adenocarcinoma <60 years of age. Veterans with stages II-IIIA squamous cell carcinoma, COPD, and CKD were optimally managed with observation. Many Veterans with comorbidities are optimally managed with observation post-surgical resection. However, we also identified several groups of Veterans whom the benefits of adjuvant chemotherapy outweighed the risks of early toxicity. Our findings could inform patient-provider discussions and potentially reduce physicians' uncertainty about the role of adjuvant chemotherapy in this population.
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Project description:BACKGROUND:The presence of comorbidities in cancer patients may influence treatment decisions and prognoses. This study aimed to examine the impact of comorbidities on overall survival in Japanese patients diagnosed with major solid tumors. METHODS:To obtain patient-level information on clinical conditions and vital status, we performed a record linkage of population-based cancer registry data from Osaka Prefecture, Japan and administrative data produced under the Diagnosis Procedure Combination (DPC) system. The study population comprised patients who received a primary diagnosis of gastric, colorectal, or lung cancer between 2010 and 2012 at any of five cancer centers. We employed the Charlson Comorbidity Index (CCI) score to quantify the impact of comorbidities on survival. The association between CCI score and survival for each cancer site was analyzed using Cox proportional hazards regression models for all-cause mortality, after adjusting for patient sex, age at cancer diagnosis, and cancer stage. RESULTS:A total of 2,609 patients with a median follow-up duration of 1,372 days were analyzed. The most frequent CCI score among the patients was 0 (77.7%), followed by 2 (14.3%). After adjusting for the covariates, we detected a significant association between CCI score and all-cause mortality. The hazard ratios per one-point increase in CCI score were 1.12 (95% confidence interval [CI], 1.02-1.23), 1.20 (95% CI, 1.08-1.34), and 1.14 (95% CI, 1.04-1.24) for gastric, colorectal, and lung cancer, respectively. CONCLUSIONS:Comorbidities have a negative prognostic impact on overall survival in cancer patients, and should be assessed as risk factors for mortality when reporting outcomes.
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Project description:Survival rates for metastatic lung cancer including non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) are poor with 5-year survival of less than 5%. The use of molecular targeted therapies has improved median overall survival (OS) in a limited group of NSCLC patients whose tumors harbor specific genetic alterations. However for a large group of NSCLC and SCLC molecular alterations are not available to lead to direct targeted therapies. Recent favorable results of newer trials of therapeutic vaccines and checkpoint inhibitors have proven against the common belief that lung cancer is nonimmunogenic. In particular, the checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and the programmed death-1 (PD-1) pathway have shown durable clinical responses with manageable toxicity. Several phase II and III clinical trials testing the association of different schedule of chemotherapy and immunotherapy or immunotherapy alone are ongoing in lung cancer and important results are expected in the near future. However, more studies are needed to understand the optimal combination of immunotherapeutic agents with chemotherapy and radiation therapy for the treatment of NSCLC and SCLC.
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Project description:Previous research had shown the number of comorbidities is a major factor influencing the burden of care for elderly patients with obstructive lung disease (OLD). This retrospective cohort study on a large population of elderly patients (age > 65 years) with OLD in northern Italy measures the use of healthcare resources associated with the most frequent combinations of comorbidities and investigates the most common reasons for hospitalization. Total health costs, pharmacy costs, emergency department (ED) visits, outpatient visits, and hospital admissions are assessed for every subject. The most common causes of hospitalization by a number of comorbidities and the most common sets of three comorbidities are identified. For each comorbidity group, we rank a list of the most frequent causes of hospitalization, both overall and avoidable with effective ambulatory care. A small group of patients suffering from major comorbidities accounts for the use of most healthcare resources. The most frequent causes of hospitalization are respiratory failure, heart failure, chronic bronchitis, and bronchopneumonia. The most common conditions manageable with ambulatory care among causes of hospitalizations are heart failure, bacterial pneumonia, and COPD. The set of three comorbidities responsible for the highest average total costs, and the highest average number of hospitalizations and outpatient visits comprised hypertension, cardiac arrhythmias, and heart failure. The main reasons for hospitalization proved to remain linked to heart failure and acute respiratory disease, regardless of specific combinations of comorbidities. Based on these findings, specific public health interventions among patients with OLD cannot be advised on the basis of specific sets of comorbidities only.
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Project description:In patients with metastatic non-small cell lung cancer (mNSCLC), the extent to which immunotherapy utilization rate varies by comorbidities is unclear. Using the National Cancer Database from 2015 to 2016, we assessed the association between levels of comorbidity and immunotherapy utilization among mNSCLC patients. Burden of comorbidities was ascertained based on the modified Charlson-Deyo score and categorized as an ordinal variable (0, 1, and ≥2). Immunotherapy utilization was determined based on registry data. Multivariable logistic regressions were used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) for the comorbidity score while adjusting for sociodemographic factors, histopathologic subtype, surgery, chemotherapy, radiotherapy, insurance, facility type, and other cancer history. Subgroup analyses were conducted by age and race/ethnicity. Overall, of the 89,030 patients with mNSCLC, 38.6% (N=34,382) had the comorbidity score of ≥1. Most patients were non-Hispanic white (82.3%, N=73,309) and aged 65 years and above (63.2%, N=56,300), with the mean age of 68.4 years (SD=10.6). Only 7.0% (N=6220) of patients received immunotherapy during 2015-2106. Patients with a comorbidity score of ≥2 had a significantly lower rate of immunotherapy utilization versus those without comorbidities (aOR=0.85; 95% CI, 0.78-0.93; P-trend<0.01). In subgroup analysis by age, association patterns were similar among patients younger than 65 and those aged 65-74 years. There were no significant differences in subgroup analysis by race/ethnicity, although statistical significance was only observed for white patients (comorbidity score ≥2 vs. 0: aOR=0.85; 95% CI, 0.77-0.93; P-trend<0.01). In conclusion, mNSCLC patients with a high burden of comorbidities are less likely to receive immunotherapy.
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