Managed Care Updates: June 2023

Quality of Life at Diagnosis Predicts Survival in Patients With Lung Cancer

Lung cancer carries a substantial symptom burden, and findings from a study published in Clinical Lung Cancer showed that physical and emotional functioning scores within quality-of-life (QOL) questionnaires at diagnosis may help predict survival in patients with lung cancer.

“Patients with lung cancer experience a higher burden of symptoms associated with physical and psychosocial problems than those with other types of cancers,” the study authors wrote. “Considerable symptom burden has been noted in newly diagnosed advanced lung cancer, and inappropriate perceptions of this burden can hinder the adequate provision of patient-centered care and further decrease patients’ QOL.”

In cancer care, several health-related QOL surveys are commonly used, including the EORTC QLQ-C30, the Edmonton Symptom Assessment System, the McGill Quality of Life Questionnaire, and the Palliative care Outcome Scale.

The EORTC QLQ-C30 has been researched as a prognostic factor in several cancer types, but prior research has often focused on the physical function aspects of the scale and left out emotional functioning measures, the authors wrote.

The current study aimed to assess the correlation between QOL as determined by the EORTC QLQ-C30 with survival in patients with lung cancer, factoring in both physical and emotional functioning measures and including possible confounding factors. The questionnaire includes 30 questions evaluating 5 functional scales (physical, role, emotional, cognitive , and social functioning) and 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties).

The multicenter study included data from 1297 patients with lung cancer across 7 medical centers of the Catholic University of Korea who were enrolled between December 2017 and December 2020. Basic demographic and disease data were collected, and QOL information was collected using the EORTC QLQ-C30 version 3.0 at diagnosis.

According to results from a multivariable analysis, several factors were significant independent predictors of survival: male sex, younger age, never smoker status, better performance status (ECOG score, 0-1), early-stage (stage I or II) disease at diagnosis, receiving treatment, higher physical functioning scores, and higher emotional functioning scores.

“Here we only analyzed functional scales with survival, not including symptom scales even though survival may also be affected by symptom burden, because the aim of our study was to evaluate the association between functions and survival,” the authors noted.

In a subgroup analysis with patients stratified into early- or advanced-stage cancer at diagnosis, higher physical function scores and higher emotional function scores were both found to be positive prognostic factors for survival. Physical function was an independent prognostic factor in early-stage lung cancer, and emotional functioning was a significant factor regardless of stage at diagnosis.

Additionally, some symptoms in the 9 scales were associated with lower functioning. Fatigue, pain, insomnia, and financial difficulties all correlated with lower emotional function scores, and fatigue, pain, dyspnea, and financial difficulties correlated with lower physical function scores. Considering functioning scale scores were found to be predictive of survival, the authors highlighted the importance of taking patient complaints about symptoms seriously to improve emotional and physical functioning when possible.

The study was limited because investigators only collected EORTC QLQ C-30 scores at diagnosis and did not conduct follow-up surveys. The patient population was also heterogeneous with varied treatment modalities, pathology types, and clinical stages, although clinical stage heterogeneity was addressed by the subgroup analysis.

Further prospective research is needed to overcome limitations and confirm the findings, but the data suggest that self-reported QOL information may be predictive of survival in lung cancer.

“Our findings suggest that physical functioning and emotional functioning, as assessed by patients’ self-report, can both independently predict survival in patients with lung cancer regardless of clinical stages, and that identifying symptoms could help improve QOL among patients with lung cancer,” the authors concluded. 

Reference

Hong YJ, Han S, Lim JU, et al. Association between quality of life questionnaire at diagnosis and survival in patients with lung cancer. Clin Lung Cancer. Published online March 20, 2023. doi:10.1016/j.cllc.2023.03.007

DNA Sequencing Prior to HCT Identifies Patients at Risk of Poor AML Outcomes

In patients with acute myeloid leukemia (AML) in first remission, the persistence of certain DNA variants related to measurable residual disease (MRD) prior to allogeneic hematopoietic cell transplant (HCT) was associated with post-HCT relapse and worse survival outcomes, according to a recent study.

The findings were published in JAMA on March 7, 2023, and suggest that the potential benefits of routine DNA testing for residual variants warrant further research in the context of AML. Although allogeneic HCT is typically recommended for maintenance of initial AML remission, disease recurrence happens in approximately 30% of patients, the study authors noted. Disease recurrence is the most common cause of death after HCT.

MRD has become a topic of interest, especially in hematological malignancies, with increasing evidence suggesting its value in predicting relapse and mortality in patients who are in cytomorphological complete remission. Despite the potential benefits, there is no standard method of MRD testing for patients with AML.

The current study aimed to determine whether the presence of specific residual AML-associated DNA variants in patients’ blood during remission but before allogeneic HCT would be associated with increased risk of relapse and mortality following HCT. Relapse-free survival and nonrelapse mortality were secondary outcomes of interest.

A total of 1075 patients from 110 US sites and 1 site in Europe were included in the retrospective, observational study. Of these patients, 454 in the discovery cohort underwent HCT between March 2013 and December 2017, and 621 in the validation cohort underwent HCT between January 2018 and February 2019.

Blood samples were collected a median of 9 days before transplant, and the discovery and validation cohorts had similar 3-year relapse rates and overall survival (OS) rates. In the discovery cohort, 131 patients (28.9%) had variants of interest, and 188 patients (30.3%) in the validation cohort showed variants in the genes of interest. Patients were tested for 5 genes of interest: NPM1, FLT3, IDH1, IDH2, and/or KIT.

In the overall cohort, 822 patients showed FLT3 internal tandem duplication (FLT3-ITD) and/or NPM1-mutated AML. Of these patients, 371 were in the discovery cohort and 451 were in the validation cohort.

In the discovery cohort, 64 patients with persistent NPM1 and/or FLT3-ITD variants while in remission before undergoing transplant showed higher post-HCT relapse and worse OS compared with patients without persistent variants.

The validation cohort showed similar outcomes. The 78 patients who showed residual NPM1 and/or FLT3-ITD variants experienced higher rates of relapse and worse OS at 3 years. Those with persistent mutations relapsed in 68% of cases compared with 21% of patients without persistent mutations. Three-year OS was 39% among those with persistent mutations and 63% among those without persistent variants.

The findings suggest that the persistence of FLT3-ITD or NPM1 variants in patients with AML during first remission but prior to HCT may be predictive of relapse and mortality. However, further research is needed to determine whether DNA sequencing can help improve outcomes in this patient population. 

Reference

Dillon LW, Gui G, Page KM, et al. DNA sequencing to detect residual disease in adults with acute myeloid leukemia prior to hematopoietic cell transplant. JAMA. 2023;329(9):745-755. doi:10.1001/jama.2023.1363