Citations

The American Geriatrics Society convened a conference in Bethesda, Maryland, to explore models and studies of aging. This was the second of three conferences, supported by a U13 grant from the National Institute on Aging, to aid recipients of Grants for Early Medical/Surgical Specialists Transition to Aging Research (GEMSSTAR) in integrating geriatrics into their specialties. Recognizing that aging is the largest risk factor for multiple chronic diseases and age‐related loss of resilience, the conference organizers focused scientific sessions on how targeting age‐related mechanisms can delay, prevent, or reverse geriatric syndromes, age‐related chronic diseases, and loss of resilience. The rationale for studying models of aging as well as study designs, strategies, and challenges of studying human aging were reviewed. This article provides a summary of the full conference report, Models and Studies of Aging: Report from the U13 Conference Series, and summarizes key take‐home messages that were designed to support GEMSSTAR awardees in developing their research careers focused on aging research (see supplementary text for the full report). J Am Geriatr Soc 67:428–433, 2019.

612 Background: mCRC is a heterogeneous disease leading to possible disparate responses among lesions in a single pt. This study assesses the heterogeneity of lesion responses and evaluates the prognostic value of LBR12 and its mortality risk discrimination beyond RECIST responses. Methods: Pts with ≥ 2 lesions and no new lesions at 12 weeks (wks) were eligible. For each pt, after 12 wks of Rx, each lesion was categorized as progressive disease (L-PD: ≥20% increase in the longest diameter [LD]), partial response (L-PR: ≥30% decrease in LD), or stable disease (L-SD: neither L-PD nor L-PR). LBR12 was defined, per patient, by the combination of lesion responses: homogeneous LBR12 (L-PD, L-SD, L-PR only) and heterogeneous LBR12 (mixture of L-PD/L-SD, L-PD/L-PR, L-SD/L-PR). LBR12 and overall survival (OS) were correlated using stratified multivariate Cox models after adjusting for age, gender, and ECOG PS. Results: Among 9,092 mCRCs (Rx: chemo alone 44%; chemo + VEGF inhibitor [VEGFi] 42%; chemo + EGFR inhibitor [EGFRi] 10%) from 16 1st-line studies. Median OS: 2.2 years. Per RECIST at 12 wks, CR 0%; PR 36.1%; SD 60.9%; PD 3.0%. Responses in 52% were heterogeneous (Table). VEGFi and EGFRi treated pts had the highest rate of L-SD/L-PR (45%) and L-PR only (22%) status, respectively. Median OS increased monotonically across pts with more L-PRs and fewer L-PDs (Table). Pts with L-SD/L-PR status, among which 51% had SD per RECIST, had longer OS than those with L-SD only status (HRadj.= .81, padj.< .0001), but shorter OS than those with L-PR only status (HRadj.= 1.46, padj.< .0001). Pts with L-PD/L-SD status, among which 71% were SD per RECIST, had shorter OS than those with L-SD only status (HRadj.= 2.22, padj.< .0001). These associations were consistent across treatment regimens. Conclusions: The lesion-based response captures the heterogeneity of within pt lesion responses and provides refinement in predicting outcome beyond RECIST response at 12 wks. [Table: see text]

3535 Background: CRC is known to be a heterogeneous disease. This study quantifies within pt heterogeneity in early lesion change rate (LCR) in the era of targeted agents compared to chemo alone and its potential impact on survival. Methods: Pts with 2-10 lesions measured at baseline were included. For each lesion, the early LCR was defined as the change in size (shrinking or growing) from baseline to 12 weeks on treatment. Within pt heterogeneity in early LCR among lesions was estimated by standard deviation (STD). A larger value of STD indicates larger variation of LCR per pt. Stratified multivariate Cox models were used to assess the associations between LCR STD with overall survival (OS). Adjusted hazard ratios (HRadj) and 95% confidence intervals (CIs) are reported. Results: Data were available on 9,092 mCRC pts (median age 61; 60% male, 55% ECOG PS 0; 61% 2+ metastatic sites) enrolled in 16 1st-line randomized trials, with 44%, 42%, and 10% of pts received chemo alone, + a VEGF inhibitor (VEGFi) or an EGFR inhibitor (EGFRi), respectively. LCR heterogeneity is the highest among pts received EGFRi but lowest among pts received VEGFi (Table). Overall, higher heterogeneity is associated with worst OS (HRadj1.22, 95% CI (1.16, 1.27)). The effect is most pronounced in pts received VEGFi (interaction p=0.0012). Conclusions: There was heterogeneity observed in lesion size changes within pts. Its magnitude varies across treatment approaches, and was associated with poor survival. This preliminary result reveals the great potentials to define novel response endpoint and refine treatment decision-making by incorporating heterogeneities in lesion changes. [Table: see text]

AbstractBackgroundAlthough the prognosis of core‐binding factor (CBF) acute myeloid leukemia (AML) is better than other subtypes of AML, 30% of patients still relapse and may require allogeneic hematopoietic cell transplantation (alloHCT). However, there is no validated widely accepted scoring system to predict patient subsets with higher risk of relapse.MethodsEleven centers in the US and Europe evaluated 247 patients with t(8;21)(q22;q22).ResultsComplete remission (CR) rate was high (92.7%), yet relapse occurred in 27.1% of patients. A total of 24.7% of patients received alloHCT. The median disease‐free (DFS) and overall (OS) survival were 20.8 and 31.2 months, respectively. Age, KIT D816V mutated (11.3%) or nontested (36.4%) compared with KIT D816V wild type (52.5%), high white blood cell counts (WBC), and pseudodiploidy compared with hyper‐ or hypodiploidy were included in a scoring system (named I‐CBFit). DFS rate at 2 years was 76% for patients with a low‐risk I‐CBFit score compared with 36% for those with a high‐risk I‐CBFit score (P < 0.0001). Low‐ vs high‐risk OS at 2 years was 89% vs 51% (P < 0.0001).ConclusionsI‐CBFit composed of readily available risk factors can be useful to tailor the therapy of patients, especially for whom alloHCT is not need in CR1 (ie, patients with a low‐risk I‐CBFit score).