Real-world Cohort Research Articles

Determining Clinicopathologic Factors That Influence Treatment in Advanced Breast Cancer in Argentina After CDK4/6 Inhibitors.

The optimal treatment sequence for hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) after progression on first-line cyclin-dependent kinase 4/6 inhibitor (CDKi) and endocrine therapy is unclear. Clinical and biological factors influencing treatment choices and outcomes in the second-line setting need to be elucidated. This is a retrospective analysis of a real-world cohort including patients with HR+/HER2- ABC who received CDKi and endocrine therapy in the first-line setting and progressed, requiring second-line treatment. Clinical and biological factors were analyzed to evaluate their association with daily treatment decisions and the prognostic role of progression-free survival (PFS) in the second-line setting. Two hundred thirty-five patients were included. Second-line treatments were hormone therapy (HT) based in 60% and chemotherapy based in 40% of patients. The second-line median PFS was 6.6 months, with no difference between treatment types. In multivariable analysis, postmenopausal status, lower Ki-67 expression, and non-de novo stage IV disease were associated with improved second-line (2L) PFS. Menopausal status significantly interacted with treatment type, with reduced PFS in premenopausal patients receiving HT-based treatments (4.7 v 8.7 months, P = .00045). In our study, treatment decisions reflected the current algorithm incorporated in our clinical guidelines, and prior treatment response was the most relevant factor to determine 2L treatment decision. Menopausal status interacted with the subsequent therapy efficacy in this setting. Hence, we consider that menopausal status should be routinely evaluated in the subgroup analysis of clinical trials.

Risk Stratification According to Baseline and Early Change in Neutrophil-to-Lymphocyte Ratio in Advanced Non-Small Cell Lung Cancer Treated with Chemoimmunotherapy: A Multicenter Real-World Study.

Chemoimmunotherapy is a standard treatment for advanced non-small-cell lung cancer (NSCLC). However, data on clinical predictive factors remain scarce. We aim to identify clinical biomarkers in patients undergoing chemoimmunotherapy. This multicenter, real-world cohort study included chemonaive patients who underwent chemoimmunotherapy between December 2018 and May 2022. Multivariate analysis was used to determine associations between survival outcomes and patient background, including baseline neutrophil-to-lymphocyte ratio (NLR) and its dynamic change (ΔNLR). To further investigate the clinical significance of NLR, patients were classified based on their peripheral immune status, defined by a combination of NLR and ΔNLR. The study included 280 patients with 30.1 months of median follow-up. Multivariate analysis revealed that older individuals, poor performance status, tumor proportion score < 1%, liver metastasis, baseline NLR ≥ 5, and ΔNLR ≥ 0 independently correlated significantly with shorter progression-free and overall survival (OS). Patients with high peripheral immune status (defined as NLR <5 and ΔNLR < 0) significantly improved long-term survival (2-year OS rate of 58.3%), whereas those with low peripheral immune status (defined as NLR ≥ 5 and ΔNLR ≥ 0) had extremely poor outcomes (2-year OS rate of 5.6%). Safety profiles did not differ significantly in terms of severe adverse events and treatment-related death rates despite the patients' peripheral immune status (P = 0.46 and 0.63, respectively). Our study provides real-world evidence regarding clinical prognostic factors for the efficacy of chemoimmunotherapy. The combined assessment of baseline NLR and ΔNLR could facilitate the identification of patients who are likely to achieve a durable response from chemoimmunotherapy.

LDL-cholesterol goal achievement and self-reported medication adherence: insights from the JET-LDL registry

In patients with recent acute coronary syndromes (ACS), current guidelines recommend a low-density lipoprotein cholesterol (LDL-C) level <55 mg/dl. Despite the widespread use of different potent lipid-lowering therapies (LLT), this goal is not always achieved, often due to poor medication adherence. In this prespecified subanalysis of the JET-LDL registry, we sought to evaluate the relationship between LDL-C targets achievement and LLT adherence in a cohort of patients hospitalized for ACS. Patients self-reported medication adherence was assessed using the Morisky Medication Adherence Scale (MMAS) at 3-months follow-up. Depending on the score obtained, the population was divided into two groups: high adherence (HA, MMAS≥6) vs low adherence (LA, MMAS<6). The occurrence of the primary-endpoint (LDL-C reduction >50% from baseline or level <55 mg/dl at 1-month) was compared between the two groups. 963 patients were included in the present analysis; in 277 cases (28.7%) a MMAS score <6 was reported (LA-group), while in the other 686 (71.3%) the score obtained was ≥6 (HA-group). No difference between the two groups was observed regarding LDL-C levels at admission and LLT prescribed at discharge. At 1-month, primary-endpoint occurred in 62.5% of cases, with a statistically significant difference between the two groups (LA 60% vs HA 65%, p-value 0.034). At multivariate logistic regression analysis, LA was identified as an independent predictor of not achieving the primary-endpoint (OR 0.48 [0.39-0.85], p-value 0.006). In conclusion, in a real-world cohort of patients with ACS, low medication adherence to LLT was a common event (28.7%), having a negative impact on LDL-C goal achievement.

Circulating monocytes as a marker of response to adalimumab in patients with hidradenitis suppurativa: A single institution, real-world cohort study

Circulating monocytes as a marker of response to adalimumab in patients with hidradenitis suppurativa: A single institution, real-world cohort study

79P Comprehensive genomic profiling provides patients access to novel matched therapies in a diverse real-world cohort of advanced lung cancer patients

79P Comprehensive genomic profiling provides patients access to novel matched therapies in a diverse real-world cohort of advanced lung cancer patients

Validation of the second revision of the international staging system (R2-ISS) for overall survival in multiple myeloma in a real-world cohort: an analysis by the Balkan myeloma study group (BMSG)

Validation of the second revision of the international staging system (R2-ISS) for overall survival in multiple myeloma in a real-world cohort: an analysis by the Balkan myeloma study group (BMSG)

567: Cavity SRS in excised brain metastases: treatment characteristics & outcomes in a real-world cohort

567: Cavity SRS in excised brain metastases: treatment characteristics & outcomes in a real-world cohort

Clinical Outcomes for Metastatic Renal Cell Carcinoma (mRCC) Patients Ineligible for Front-line Clinical Trials.

Clinical trials for immunotherapy-based regimens in metastatic renal cell carcinoma (mRCC) have extensive inclusion and exclusion criteria. We investigated the clinical outcomes in a real-world cohort of patients who would not have met the criteria for inclusion in front-line mRCC trials. Patients treated with ipilimumab/nivolumab and axitinib/pembrolizumab for front-line mRCC were identified and divided into clinical trial eligible (CTE) and clinical trial ineligible (CTI) cohorts based on key inclusion or exclusion criteria from their respective Phase-3 registration trials. Clinical outcomes were compared in CTE and CTI cohorts. A total of 62 patients treated with axitinib/pembrolizumab and 103 treated with ipilimumab/nivolumab were identified. The International Metastatic RCC Database Consortium (IMDC) criteria were similar across CTE and CTI patients in axitinib/pembrolizumab and ipilimumab/nivolumab cohorts. In the axitinib/pembrolizumab cohort (n = 62), 24 (39%) patients were CTI. The major reasons for the ineligibility were lab abnormalities (n = 11), histology (n = 9), and brain metastases (n = 3). There was no significant difference in response rates (P = 0.08). The median progression-free survival (PFS) was numerically longer in CTE patients (28 vs 12 months; P = 0.09). The overall survival (OS) was higher in the CTE patients (P = 0.02). In the ipilimumab/nivolumab cohort (n = 103), 59 (57%) were CTI. The most common reasons for ineligibility were brain metastases (n = 18), lab abnormalities (n = 16), and histology (n = 16). There was no significant difference in response rates (P = 0.22). However, PFS (P = 0.003) and OS (P < 0.0001) were higher in the CTE patients. In conclusion, many real-world patients are ineligible for RCC clinical trials and had worse outcomes when compared to trial-eligible patients. Additional treatment options are needed for these patients, as well as strategies to include them in prospective trials.

Initial Trans-Arterial Chemo-Embolisation (TACE) Is Associated with Similar Survival Outcomes as Compared to Upfront Percutaneous Ablation Allowing for Follow-Up Treatment in Those with Single Hepatocellular Carcinoma (HCC) ≤ 3 cm: Results of a Real-World Propensity-Matched Multi-Centre Australian Cohort Study.

Percutaneous ablation is recommended in Barcelona Clinic Liver Cancer (BCLC) stage 0/A patients with HCC ≤3 cm as a curative treatment modality alongside surgical resection and liver transplantation. However, trans-arterial chemo-embolisation (TACE) is commonly used in the real-world as an initial treatment in patients with single small HCC in contrast to widely accepted clinical practice guidelines which typically describe TACE as a treatment for intermediate-stage HCC. We performed this real-world propensity-matched multi-centre cohort study in patients with single HCC ≤ 3 cm to assess for differences in survival outcomes between those undergoing initial TACE and those receiving upfront ablation. Patients with a new diagnosis of BCLC 0/A HCC with a single tumour ≤3 cm first diagnosed between 1 January 2016 and 31 December 2020 who received initial TACE or ablation were included in the study. A total of 348 patients were included in the study, with 147 patients receiving initial TACE and 201 patients undergoing upfront ablation. After propensity score matching using key covariates, 230 patients were available for analysis with 115 in each group. There were no significant differences in overall survival (log-rank test p = 0.652) or liver-related survival (log-rank test p = 0.495) over a median follow-up of 43 months. While rates of CR were superior after ablation compared to TACE as a first treatment (74% vs. 56%, p < 0.004), there was no significant difference in CR rates when allowing for further subsequent treatments (86% vs. 80% p = 0.219). In those who achieved CR, recurrence-free survival and local recurrence-free survival were similar (log rank test p = 0.355 and p = 0.390, respectively). Our study provides valuable real-world evidence that TACE when offered with appropriate follow-up treatment is a reasonable initial management strategy in very early/early-stage HCC, with similar survival outcomes as compared to those managed with upfront ablation. Further work is needed to better define the role for TACE in BCLC 0/A HCC.

Prognostic Factors in Japanese EGFR Mutation-Positive Non-Small-Cell Lung Cancer: A Real-World Single-Center Retrospective Cohort Study.

The prognosis of patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer has improved significantly since the advent of EGFR tyrosine kinase inhibitors (EGFR-TKIs). We aimed to investigate the relationship between patient characteristics, EGFR genotype, therapeutic agents, and the prognosis of the patients with EGFR mutation-positive lung cancer. This retrospective cohort study analyzed 198 Japanese patients with unresectable EGFR mutation-positive lung cancer who were treated with EGFR-TKIs at Toho University Sakura Medical Center from April 2006 to December 2021. Factors associated with overall survival (OS) were analyzed using Cox proportional hazards analysis. Patients who received osimertinib had a significantly longer OS than did those not receiving it (median OS, 36.2 versus 20.7 months; p < 0.001).There were significant differences in OS between patients with EGFR mutation who received osimertinib as first-line treatment, T790M-positive patients who received osimertinib as second- or later-line treatment, and those who did not receive it (median OS, 28.2 versus 40.2 versus 20.7 months; p = 0.003). However, in T790M-negative patients, no significant difference in OS was noted between those who did and did not receive osimertinib as post-treatment (median OS, 28.0 versus 40.0 months; p = 0.619). Multivariate Cox proportional hazards analysis showed that osimertinib treatment was associated with longer OS (hazard ratio, 0.480; 95% confidence interval, 0.326-0.707; p < 0.001). The patients who were T790M-positive in the first-line treatment with first or second-generation EGFR-TKIs and were given osimertinib as the second or later line treatment had a better prognosis than the patients who were T790M-negative in the first-line treatment with first or second-generation EGFR-TKIs and could not receive osimertinib.

Cabozantinib Plus Nivolumab in Adult Patients with Advanced or Metastatic Renal Cell Carcinoma: A Retrospective, Non-Interventional Study in a Real-World Cohort/GUARDIANS Project.

Combinations of immune-checkpoint inhibitors (ICIs) are the standard of care (SOC) for treatment-naive metastatic renal cell carcinoma (mRCC) patients. In this multicenter study, we evaluated the RW safety and efficacy of cabozantinib plus nivolumab in mRCC patients. Data were retrospectively collected from twelve cancer centers in Germany, Switzerland, and Austria. Patients with advanced or mRCC were eligible. The investigator-based objective response rate (ORR) and progression free survival (PFS) were calculated from the start of the treatment to progression or death. Descriptive statistics and Kaplan-Meier (KM) plots were utilized where appropriate. In total, 96 eligible patients (66.6% male) with a median age of 66.0 years were included. The most common histology was clear-cell RCC (ccRCC) in 63.4% (n = 61). A prior nephrectomy was performed in 60.4% (n = 58). ECOG 0-1 was 68.8% (n = 66). A partial response was documented in 43.8% of patients (n = 42), a stable disease in 32.3% (n = 31), and a progressive disease in 8.3% (n = 8) as the best overall response. Response data were not evaluable in 13.5% (n = 13). The median follow-up time was 12.7 months (95% CI, 10.0-15.3). The PFS rate at 6 months was 89.8% in the overall population (86.8% for ccRCC; 90.0% for non-ccRCC). Adverse events (AEs) were reported in 82.3% (n = 79) for all grades and 41.7% (n = 40) for grades 3-5. Elevated liver enzymes (34.4%), diarrhea (31.3%), and hand-foot syndrome (29.2%) were the three most frequent AEs of any grade and causality. In this real-world cohort of mRCC patients, the application of cabozantinib plus nivolumab was shown to be safe and feasible. Our data support the use of cabozantinib plus nivolumab as a first-line standard therapy in mRCC patients. Major limitations were the retrospective data capture and short follow-up time of our study.

Automated data collection tool for real-world cohort studies of chronic hepatitis B: Leveraging OCR and NLP technologies for improved efficiency

BackgroundCollecting and standardizing clinical research data is a very tedious task. This study is to develop an intelligent data collection tool, named CHB-EDC, for real-world cohort studies of chronic hepatitis B (CHB), which can assist in standardized and efficient data collection. MethodsCHB_EDC is capable of automatically processing various formats of data, including raw data in image format, using internationally recognized data standards, OCR, and NLP models. It can automatically populate the data into eCRFs designed in the REDCap system, supporting the integration of patient data from electronic medical record systems through commonly used web application interfaces. This tool enables intelligent extraction and aggregation of data, as well as secure and anonymous data sharing. ResultsFor non-electronic data collection, the average accuracy of manual collection was 98.65 %, with an average time of 63.64 min to collect information for one patient. The average accuracy CHB-EDC was 98.66 %, with an average time of 3.57 min to collect information for one patient. In the same data collection task, CHB-EDC achieved a comparable average accuracy to manual collection. However, in terms of time, CHB-EDC significantly outperformed manual collection (p < 0.05). Our research has significantly reduced the required collection time and lowered the cost of data collection while ensuring accuracy. ConclusionThe tool has significantly improved the efficiency of data collection while ensuring accuracy, enabling standardized collection of real-world data.

Radiation Dose-Induced Carotid Artery Stenosis and Brain Necrosis in Head and Neck Cancer-A Real World Cohort Study.

Objective: This study aims to examine whether radiation therapy doses are related to incidences of carotid artery stenosis and brain necrosis in a large-scale real-world database. Methods: We identified a cohort of HNC patients from the catastrophic illness patient dataset using ICD-9 or ICD-10 to compare the incidence and risks of carotid artery stenosis (CAS) and brain necrosis (RIBN) in patients who received a radiation therapy dose of ≥5400 cGy/30 fractions (group A) with those who received a radiation therapy dose of <5400 cGy/30 fractions (group B). The incidence and hazard ratios were quantified using Cox proportional hazards models. Results: A total of 19,964 patients were identified in group A and group B. Among them, 965 and 863 cases of CAS and 435 and 359 cases of RIBN were identified in group A and group B, respectively. There was no statistically significant association between the two groups for CAS risk, whereas there was a statistically significant association between the two groups for RIBN risk. The most common primary site of head and neck cancers was the nasopharynx (1144 of 19,964, 5.73%). Conclusions: Our study suggests that RT may increase the risk of carotid stenosis and brain necrosis in patients with NPC. To ensure patient safety during treatment, the optimal balance between tumor control and toxicity prevention in individual patients through minimization of the radiation dose to all relevant OARs must be properly understood.

Clinical implications of nintedanib pharmacokinetics in patients with pulmonary fibrosis

BackgroundNintedanib is used to treat both idiopathic and progressive pulmonary fibrosis (IPF/PPF). Evidence of both an exposure-response relationship and an exposure-toxicity relationship has been found, suggesting the potential value of therapeutic drug monitoring (TDM). We aimed to define the therapeutic window of nintedanib in a real-world cohort. MethodsData from two clinical studies were pooled for this analysis. To quantify exposure to nintedanib, a population-pharmacokinetic (PK) model was developed. Associations between PK and decline in forced vital capacity (FVC) and diffusing capacity (DLCO) were performed using linear-mixed-effect models (LMEM). The exposure-toxicity relationship was evaluated using a Cox proportional hazards model. ResultsIn total, 911 PK samples from 99 patients were used to develop the PK model. The LMEM with random slopes and intercepts included 517 pulmonary function tests (PFT) from 81 patients. The average administered nintedanib dose was associated with the rate of FVC decline (p=0.002). Per 50 mg decrease of daily dosage, the rate of FVC decline increased by 53.5 mL/year. Neither nintedanib exposure nor dose significantly affected DLCO decline and they were also not significantly associated with the occurrence of a dose-limiting toxicity (DLT). This may be explained by a large inter- and intrapatient variability in nintedanib PK. ConclusionNintedanib dose was significantly associated with FVC loss. However, no significant relationship between nintedanib exposure and the occurrence of DLTs was found in this real-world population, and no therapeutic window could be established. The findings in this study indicate that nintedanib is an unsuitable candidate for performing TDM.

Patterns of Disease, Risk Factors, and Treatment in Chronic Lymphocytic Leukemia (CLL): A Retrospective Report of a Real-World Patient Cohort From the United Arab Emirates

Patterns of Disease, Risk Factors, and Treatment in Chronic Lymphocytic Leukemia (CLL): A Retrospective Report of a Real-World Patient Cohort From the United Arab Emirates

Similar Safety Profile for Rituximab and Obinutuzumab as Maintenance for Follicular Lymphoma: Evidence From a Real-World Multicenter Retrospective Cohort Study

Similar Safety Profile for Rituximab and Obinutuzumab as Maintenance for Follicular Lymphoma: Evidence From a Real-World Multicenter Retrospective Cohort Study

CLL-021 Patterns of Disease, Risk Factors, and Treatment in Chronic Lymphocytic Leukemia (CLL): A Retrospective Report of a Real-world Patient Cohort From the United Arab Emirates

CLL-021 Patterns of Disease, Risk Factors, and Treatment in Chronic Lymphocytic Leukemia (CLL): A Retrospective Report of a Real-world Patient Cohort From the United Arab Emirates

Unveiling severe adverse events of antithyroid drugs in patients with graves' disease; a real-world multicenter cohort study

Unveiling severe adverse events of antithyroid drugs in patients with graves' disease; a real-world multicenter cohort study

T3 analogue triiodothyroacetic acid (TRIAC) treatment and survival in MCT8 deficiency: an international real-world cohort study

T3 analogue triiodothyroacetic acid (TRIAC) treatment and survival in MCT8 deficiency: an international real-world cohort study

National Landscape of Neoadjuvant Therapy in Potentially Resectable Colon Cancer

IntroductionSurgery followed by pathology-guided adjuvant therapy is standard treatment for colon cancer. Data from the FOxTROT clinical trial showed potential benefit of a 6-wk neoadjuvant chemotherapy (NACT) in T3/T4 patients. The present study evaluated real-world outcomes of neoadjuvant therapy in a national cohort of patients with resectable colon cancer. Methods169,120 patients with clinical stage I, II, or III colon cancer from the National Cancer Database registry were included. Patients were categorized as having received neoadjuvant therapy followed by surgery (NACT), surgery then adjuvant chemotherapy (AC), or surgery alone. Factors associated with treatment sequencing and outcomes were assessed. ResultsOf identified patients, 1.4% received NACT including 0.5% of stage I, 1.8% of stage II, and 3.0% of stage III. For stage I, 5-y overall survival (OS) was 74.7% after AC, 62.2% after NACT, and 76.4% after SA. For stage II, 5-y OS was 73.2% after AC, 66.8% after NACT, and 64.3% after SA. For stage III, 5-y OS was 67.3% after AC, 67.7% after NACT, and 42.4% after SA. Cox proportional-hazards model suggested NACT had worse outcomes versus AC in clinical stages I (hazard ratio [HR] = 1.59, 95% confidence interval [CI] 1.39-1.85, P < 0.01) and II (HR = 1.37, 95% CI 1.23-1.52, P < 0.01). In stage III, there was no difference in OS between NACT and AC (HR = 1.1, 95% CI 0.99-1.22, P = 0.05). ConclusionsIn a real-world national cohort of patients with resectable colon cancer, NACT had no OS benefit over AC. Future studies should examine which subset of patients might benefit from neoadjuvant approaches.