A note on quantifying follow-up in studies of failure time
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Cited by (2049)
Real-world outcomes of Italian patients with advanced non-squamous lung cancer treated with first-line pembrolizumab plus platinum-pemetrexed
2024, European Journal of CancerThe aim of this multi-center, retrospective/prospective cohort observational study was to evaluate outcomes in routine clinical practice of first-line chemo-immunotherapy with cis/carboplatin, pemetrexed and pembrolizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC) in 33 Italian centers.
The outcome measure was to evaluate overall survival (OS) in a real-world patient population. Secondary endpoints were: progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and incidence of treatment-related adverse events (AEs).
1068 patients were enrolled at the time of data cut-off (January 31st, 2023), and 812 (76.0%) belonged to the retrospective cohort. Median age was 66 years (27−85), ECOG PS was ≥ 2 in 91 (8.6%) patients; 254 (23.8%) patients had brain metastases at baseline; 38 (3.6%) patients had tumor with PD-L1 expression ≥ 50%. After a median follow-up of 17.0 months (95% CI, 16.1–17.9), median OS was 16.1 months (95% CI, 14.4–18.8) and PFS was 9.9 months (95% CI, 8.8–11.2). Median DoR (n = 493) was 14.7 months (95% CI, 13.6–17.1). ORR was 43.4% (95% CI, 40.4–46.4). Any-grade AEs occurred in 636 (59.6%) patients and grade ≥ 3 in 253 (23.7%) patients. Most common grade ≥ 3 AEs were neutropenia (6.3%) and anemia (6.3%).
First-line chemo-immunotherapy was effective and tolerable in this large, real-world Italian study of patients with advanced non-squamous NSCLC. Our results were in line with the KEYNOTE-189 registration study, also considering the low number of PD-L1 ≥ 50% patients included in our study.
Interplay between B7–H3 and HLA class I in the clinical course of pancreatic ductal adenocarcinoma
2024, Cancer LettersHuman leukocyte antigen (HLA) class I defects are associated with cancer progression. However, their prognostic significance is controversial and may be modulated by immune checkpoints. Here, we investigated whether the checkpoint B7–H3 modulates the relationship between HLA class I and pancreatic ductal adenocarcinoma (PDAC) prognosis.
PDAC tumors were analyzed for the expression of B7–H3, HLA class I, HLA class II molecules, and for the presence of tumor-infiltrating immune cells. We observed defective HLA class I and HLA class II expressions in 75% and 59% of PDAC samples, respectively. HLA class I and B7–H3 expression were positively related at mRNA and protein level, potentially because of shared regulation by RELA, a sub-unit of NF-kB. High B7–H3 expression and low CD8+ T cell density were indicators of poor survival, while HLA class I was not. Defective HLA class I expression was associated with unfavorable survival only in patients with low B7–H3 expression.
Favorable survival was observed only when HLA class I expression was high and B7–H3 expression low.
Our results provide the rationale for targeting B7–H3 in patients with PDAC tumors displaying high HLA class I levels.
Sotorasib in KRAS G12C-mutated non-small cell lung cancer: A multicenter real-world experience from the compassionate use program in Germany
2024, European Journal of CancerSotorasib is a first-in-class KRAS p.G12C-inhibitor that has entered clinical trials in pretreated patients with non-small cell lung cancer (NSCLC) in 2018. First response rates were promising in the CodeBreaK trials. It remains unclear whether response to sotorasib and outcomes differ in a real-world setting when including patients underrepresented in clinical trials.
Patients with KRAS p.G12C-mutated advanced or metastatic NSCLC received sotorasib within the German multicenter sotorasib compassionate use program between 2020 to 2022. Data on efficacy, tolerability, and survival were analyzed in the full cohort and in subgroups of special interest such as co-occurring mutations and across PD-L1 expression levels.
We analyzed 163 patients who received sotorasib after a median of two treatment lines (range, 0 to 7). Every fourth patient had a poor performance status and 38% had brain metastases (BM). The objective response rate was 38.7%. The median overall survival was 9.8 months (95% CI, 6.5 to not reached). Median real-world (rw) progression-free survival was 4.8 months (9% CI, 3.9 to 5.9). Dose reductions and permanent discontinuation were necessary in 35 (21.5%) and 7 (4.3%) patients, respectively. Efficacy seems to be influenced by PD-L1 expression and a co-occurring KEAP1 mutation. KEAP1 was associated with an inferior survival. Other factors such as BM, STK11, and TP53 mutations had no impact on response and survival.
First results from a real-world population confirm promising efficacy of sotorasib for the treatment of advanced KRAS p.G12C-mutated NSCLC. Patients with co-occurring KEAP1 mutations seem to derive less benefit.
Derivation of an Annualized Claims-Based Major Adverse Cardiovascular Event Estimator in Type 2 Diabetes
2024, JACC: AdvancesMajor adverse cardiovascular events (MACE) are a leading cause of morbidity and mortality among adults with type 2 diabetes. Currently, available MACE prediction models have important limitations, including reliance on data that may not be routinely available, narrow focus on primary prevention, limited patient populations, and longtime horizons for risk prediction.
The purpose of this study was to derive and internally validate a claims-based prediction model for 1-year risk of MACE in type 2 diabetes.
Using medical and pharmacy claims for adults with type 2 diabetes enrolled in commercial, Medicare Advantage, and Medicare fee-for-service plans between 2014 and 2021, we derived and internally validated the annualized claims-based MACE estimator (ACME) model to predict the risk of MACE (nonfatal acute myocardial infarction, nonfatal stroke, and all-cause mortality). The Cox proportional hazards model was composed of 30 covariates, including patient age, sex, comorbidities, and medications.
The study cohort comprised 6,623,526 adults with type 2 diabetes, mean age 68.1 ± 10.6 years, 49.8% women, and 73.0% Non-Hispanic White. ACME had a concordance index of 0.74 (validation index range: 0.739-0.741). The predicted 1-year risk of the study cohort ranged from 0.4% to 99.9%, with a median risk of 3.4% (IQR: 2.3%-6.5%).
ACME was derived in a large usual care population, relies on routinely available data, and estimates short-term MACE risk. It can support population risk stratification at the health system and payer levels, participant identification for decentralized clinical trials of cardiovascular disease, and risk-stratified observational studies using real-world data.
Comparison of the prognostic value of eight nutrition-related tools in older patients with cancer: A prospective study
2024, Journal of Nutrition, Health and AgingThe primary objective of the present study was to evaluate and compare the ability of eight nutrition-related tools to predict 1-year mortality in older patients with cancer.
We studied older patients with cancer from the ELCAPA cohort and who had been referred for a geriatric assessment at one of 14 participating geriatric oncology clinics in the greater Paris area of France between 2007 and 2018.
The studied nutrition-related tools/markers were the body mass index (BMI), weight loss (WL) in the previous 6 months, the Mini Nutritional Assessment, the Geriatric Nutritional Risk Index (GNRI), the Prognostic Nutritional Index, the Glasgow Prognostic Score (GPS), the modified GPS, and the C-reactive protein/albumin ratio.
A total of 1361 patients (median age: 81; males: 51%; metastatic cancer: 49%) were included in the analysis. Most of the tools showed a progressively increase in the mortality risk as the nutrition-related risk category worsened (overall p-values <0.02 for all) after adjustment for age, outpatient status, functional status, severe comorbidities, cognition, mood, cancer treatment strategy, tumour site, and tumour metastasis. All the models were discriminant, with a C-index ranging from 0.748 (for the BMI) to 0.762 (for the GPS). The concordance probability estimate ranged from 0.764 (WL) to 0.773 (GNRI and GPS)).
After adjustment for relevant prognostic factors, all eight nutrition-related tools/markers were independently associated with 1-year mortality in older patients with cancer. Depending on the time or context of the GA, physicians do not always have the time or means to perform and assess all the tools/markers compared here. However, even when some information is missing, each nutritional tool/marker has prognostic value and can be used in the evaluation.
Improving survival in advanced melanoma patients: a trend analysis from 2013 to 2021
2024, eClinicalMedicineThe prognosis of advanced melanoma patients has significantly improved over the years. We aimed to evaluate the survival per year of diagnosis.
All systemically treated patients diagnosed with advanced melanoma from 2013 to 2021 were included from the Dutch Melanoma Treatment Registry. Baseline characteristics and overall survival (OS) were compared between the different years of diagnosis. A multivariable Cox proportional hazards model was used to estimate the association between year of diagnosis and OS.
For this cohort study, we included 6260 systemically treated advanced melanoma patients. At baseline, there was an increase over the years in age, the percentage of patients with an ECOG PS ≥ 2, with brain metastases, and a synchronous diagnosis of primary and unresectable melanoma. Median OS increased from 11.2 months (95% CI 10.0–12.4) for patients diagnosed in 2013 to 32.0 months (95% CI 26.6–36.7) for patients diagnosed in 2019. Median OS was remarkably lower for patients diagnosed in 2020 (26.6 months; 95% CI 23.9–35.1) and 2021 (24.0 months; 95% CI 20.4-NR). Patients diagnosed in 2020 and 2021 had a higher hazard of death compared to patients diagnosed in 2019, although this was not significant. The multivariable Cox regression showed a lower hazard of death for the years of diagnosis after 2013. In contrast, patients diagnosed in 2020 and 2021 had a higher hazard of death compared to patients diagnosed in 2019.
After a continuous survival improvement for advanced melanoma patients between 2013 and 2019, outcomes of patients diagnosed in 2020 and 2021 seem poorer. This trend of decreased survival remained after correcting for known prognostic factors and previous neoadjuvant or adjuvant treatment, suggesting that it is explained by unmeasured factors, which—considering the timing—could be COVID-19-related.
For the Dutch Melanoma Treatment Registry (DMTR), the Dutch Institute for Clinical Auditing foundation received a start-up grant from governmental organization The Netherlands Organization for Health Research and Development (ZonMW, project number 836002002). The DMTR is structurally funded by Bristol-Myers Squibb, Merck Sharpe & Dohme, Novartis, and Roche Pharma. Roche Pharma stopped funding in 2019, and Pierre Fabre started funding the DMTR in 2019. For this work, no funding was granted.