Person:

Nipp, Ryan

Background. Studies demonstrate that early palliative care (EPC) improves advanced cancer patients’ quality of life (QOL) and mood. However, it remains unclear whether the role of palliative care differs based upon patients’ demographic characteristics. We explored whether age and gender moderate the improvements in QOL and mood seen with EPC. Methods. We performed a secondary analysis of data from a randomized controlled trial of patients with metastatic non-small cell lung cancer. Patients received either EPC integrated with oncology care or oncology care alone. We assessed the degree to which QOL (Trial Outcome Index [TOI]) and mood (Hospital Anxiety and Depression Scale [HADS] and Patient Health Questionnaire 9 [PHQ-9]) outcomes at week 12 varied by patient age (<65) and gender. The week 12 data of 107 patients are included in this analysis. Results. At 12 weeks, younger patients receiving EPC reported better QOL (TOI mean = 62.04 vs. 49.43, p = .001) and lower rates of depression (HADS–Depression = 4.0% vs. 52.4%, p < .001; PHQ-9 = 0.0% vs. 28.6%, p = .006) than younger patients receiving oncology care alone. Males receiving EPC reported better QOL (TOI mean = 58.81 vs. 48.30, p = .001) and lower rates of depression (HADS–Depression = 18.5% vs. 60.9%, p = .002; PHQ-9 = 3.8% vs. 34.8%, p = .008) than males receiving oncology care alone. At 12 weeks, QOL and mood did not differ between study groups for females and older patients. Conclusion. Males and younger patients who received EPC had better QOL and mood than those who received oncology care alone. However, these outcomes did not differ significantly between treatment groups for females or older patients. Implications for Practice: This study found that early palliative care improves patients’ quality of life and mood differentially based on their age and gender. Specifically, males and younger patients receiving early palliative care experienced better quality of life and mood than those receiving oncology care alone. Conversely, females and older patients did not experience this treatment effect. Thus, palliative care interventions may need to be tailored to patients’ age- and gender-specific care needs. Studying how patients’ demographic characteristics affect their experience with palliative care will enable the development of interventions targeted to the distinct supportive care needs of patients with cancer.

In this editorial, the generalizability of trial results to the geriatric population is discussed. Specifically, the results from a recent observational study are compared with results from the SHARP trial, and recommendations are made for bridging the gap between efficacy and effectiveness in clinical research, particularly with regard to older patients.

Abstract Age, sex, and racial/ethnic disparities exist, but are understudied in pancreatic adenocarcinoma (PDAC). We used the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database to determine whether survival and treatment disparities persist after adjusting for demographic and clinical characteristics. Our study included PDAC patients diagnosed between 1992 and 2011. We used Cox regression to compare survival across age, sex, and race/ethnicity within early‐stage and late‐stage cancer subgroups, adjusting for marital status, urban location, socioeconomics, SEER region, comorbidities, stage, lymph node status, tumor location, tumor grade, diagnosis year, and treatment received. We used logistic regression to compare differences in treatment received across age, sex, and race/ethnicity. Among 20,896 patients, 84% were White, 9% Black, 5% Asian, and 2% Hispanic. Median age was 75; 56% were female and 53% had late‐stage cancer. Among early‐stage patients in the adjusted Cox model, older patient subgroups had worse survival compared with ages 66–69 (HR > 1.1, P < 0.01 for groups >69); no survival differences existed between sexes. Black (HR = 1.1, P = 0.01) and Hispanic (HR = 1.2, P < 0.01) patients had worse survival compared with White. Among late‐stage cancer patients, patients over age 84 had worse survival than those aged 66–69 (HR = 1.1, P < 0.01), and males (HR = 1.08, P < 0.01) had worse survival than females; there were no racial/ethnic differences. Older age and minority race/ethnicity were associated with lower likelihood of receiving chemotherapy, radiation, and/or surgery. Age and racial/ethnic disparities in survival outcomes and treatment received exist for PDAC patients; these disparities persist after adjusting for differences in demographic and clinical characteristics.

During cancer therapy, tumor heterogeneity can drive the evolution of multiple tumor subclones harboring unique resistance mechanisms in an individual patient1-3. Prior case reports and small case series have suggested that liquid biopsy (specifically, cell-free DNA (cfDNA)) may better capture the heterogeneity of acquired resistance4-8. However, the effectiveness of cfDNA versus standard single-lesion tumor biopsies has not been directly compared in larger scale prospective cohorts of patients following progression on targeted therapy. Here, in a prospective cohort of 42 patients with molecularly-defined gastrointestinal cancers and acquired resistance to targeted therapy, direct comparison of post-progression cfDNA versus tumor biopsy revealed that cfDNA more frequently identified clinically-relevant resistance alterations and multiple resistance mechanisms, detecting resistance alterations not found in the matched tumor biopsy in 78% of cases. Whole-exome sequencing of serial cfDNA, tumor biopsies, and rapid autopsy specimens elucidated substantial geographic and evolutionary differences across lesions. Our data suggest that acquired resistance is frequently characterized by profound tumor heterogeneity, and that the emergence of multiple resistance alterations in an individual patient may represent the “rule” rather than the “exception.” These findings have profound therapeutic implications and highlight the potential advantages of cfDNA over tissue biopsy in the setting of acquired resistance.