Sarcopenia as the Mobility Phenotype of Aging: Clinical Implications.

Sarcopenia, which is characterized by an age-related decline in muscle mass and function, poses significant challenges to geriatric care. Its definition has evolved from muscle-specific criteria to include muscle mass, muscle function, and physical performance, recognizing sarcopenia as a physical frailty. Sarcopenia is associated with adverse outcomes, including mortality, falls, fractures, cognitive decline, and admission to long-term care facilities. Neuromechanical factors, protein-energy balance, and muscle protein synthesis-breakdown mechanisms contribute to its pathophysiology. The identification of sarcopenia involves screening tests and a comprehensive assessment of muscle mass, strength, and physical function. Clinical approaches aligned with the principles of comprehensive geriatric assessment prioritize patient-centered care. This assessment aids in identifying issues related to activities of daily living, cognition, mood, nutrition, and social support, alongside other aspects. The general approach to factors underlying muscle loss and functional decline in patients with sarcopenia includes managing chronic diseases and evaluating administered medications, with interventions including exercise and nutrition, as well as evolving pharmacological options. Ongoing research targeting pathways, such as myostatin-activin and exercise mimetics, holds promise for pharmacological interventions. In summary, sarcopenia requires a multifaceted approach, acknowledging its complex etiology and tailoring interventions to individual patient needs.

Frailty is not an independent risk factor for worse clinical outcomes in lumbar spinal surgery: a prospective cohort study.

PURPOSE: Recently, many studies revealed that frailty affects unfavorably on postoperative outcomes in lumbar spinal diseases. This study aimed to investigate the relationship between frailty and clinical outcomes while identifying risk factors associated with worse clinical outcomes following lumbar spinal surgery. METHODS: From March 2019 to February 2021, we prospectively enrolled eligible patients with degenerative lumbar spinal diseases requiring surgery. Frailty was assessed preoperatively. To identify the impact of frailty on lumbar spinal diseases, clinical outcomes, which were measured with patient-reported outcomes (PROs) and postoperative complications, were compared according to the frailty. PROs were assessed preoperatively and one year postoperatively. In addition, risk factors for preoperative and postoperative worse clinical outcomes were investigated. RESULTS: PROs were constantly lower in the frail group than in the non-frail group before and after surgery, and the change of PROs between before and after surgery and postoperative complications were not different between the groups. In addition, frailty was a persistent risk factor for postoperative worse clinical outcome before and after surgery in lumbar spinal surgery. CONCLUSION: Frailty persistently affects the clinical outcome negatively before and after surgery in lumbar spinal surgery. However, as the change of the clinical outcome is not different between the frail group and the non-frail group, it is difficult to interpret whether the frail patients are vulnerable to the surgery. In conclusion, frailty is not an independent risk factor for worse clinical outcome in lumbar spinal surgery.

A Phase 1b/2a Study of GC1118 with 5-Fluorouracil, Leucovorin and Irinotecan (FOLFIRI) in Patients with Recurrent or Metastatic Colorectal Cancer.

PURPOSE: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). MATERIALS AND METHODS: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. RESULTS: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). CONCLUSION: GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Circulating lumican as a potential biomarker for osteosarcopenia in older adults.

In vitro and animal experiments demonstrated that lumican exerts anabolic effects on bone and muscle by stimulating osteoblastogenesis, suppressing osteoclastogenesis and increasing myogenesis. However, the relationship between circulating lumican and musculoskeletal phenotypes in humans remains unclear. We aimed to analyze the relationship between serum lumican levels and osteosarcopenia in older adults. Blood samples were collected from 134 participants (age: 65 years and older) who underwent comprehensive assessment of bone and muscle phenotypes. Osteoporosis and sarcopenia were diagnosed based on World Health Organization and Asian consensus guidelines, respectively. Osteosarcopenia was defined as the simultaneous presence of osteoporosis and sarcopenia. After adjusting for sex, age, and body mass index, older adults with osteosarcopenia had 20.2 % lower serum lumican levels than those without (P = 0.010). The odds ratio (OR) for osteosarcopenia per standard deviation decrease in serum lumican level was 4.17 (P = 0.003). Consistently, higher serum lumican levels were correlated with higher bone mass at all measured sites (P = 0.004 to 0.045) and higher grip strength (P = 0.023). Furthermore, participants in the lowest tertile (T1) had 7.56-fold higher OR for osteosarcopenia (P = 0.024) than those in the highest lumican tertile (T3). In conclusion, these findings clinically validate previous experimental data showing the musculoskeletal protective effects of lumican and suggest that blood lumican levels could be used as a potential biomarker to assess the risk of not only osteosarcopenia but also osteoporosis or sarcopenia in older adults.

Phenotype validation of the Korean working group on sarcopenia guideline.

BACKGROUND: This study aimed to validate the proposed Korean Working Group on Sarcopenia (KWGS) guideline, which introduces the concept of functional sarcopenia, in older Korean adults. METHODS: Data from the Aging Study of Pyeongchang Rural Area, a longitudinal cohort of community-dwelling older adults, were utilized to compare frailty status and institutionalization-free survival among participants according to sarcopenia status. Based on the KWGS guideline, severe sarcopenia was defined as low muscle mass and strength with slow gait speed; sarcopenia (not severe) was defined as low muscle mass with low muscle strength or slow gait speed; and functional sarcopenia was defined as low muscle strength and slow gait speed without low muscle mass. RESULTS: Among the 1302 participants, 329 (25.3 %) had severe sarcopenia, 147 (11.3 %) had sarcopenia (not severe), and 277 (21.3 %) had functional sarcopenia. Frailty was significantly greater in participants with any phenotype of sarcopenia than in those without sarcopenia. Additionally, participants with functional sarcopenia were frailer than those with sarcopenia (not severe). Furthermore, the rates of institutionalization and mortality were higher in participants with any phenotype of sarcopenia than in those without sarcopenia. There was no statistical difference between the rates of sarcopenia (not severe) and those with functional sarcopenia. These findings remained consistent after adjusting for age and sex. CONCLUSIONS: Each phenotype according to the KWGS guideline was associated with significantly greater frailty and increased risk of institutionalization and mortality. Functional sarcopenia was associated with greater frailty and had comparable prognosis with sarcopenia (not severe).

Higher Plasma Stromal Cell-Derived Factor 1 Is Associated with Lower Risk for Sarcopenia in Older Asian Adults.

BACKGRUOUND: Despite the protective effects of stromal cell-derived factor 1 (SDF-1) in stimulating muscle regeneration shown in experimental research, there is a lack of clinical studies linking circulating SDF-1 concentrations with muscle phenotypes. In order to elucidate the role of SDF-1 as a potential biomarker reflecting human muscle health, we investigated the association of plasma SDF-1 levels with sarcopenia in older adults. METHODS: This cross-sectional study included 97 community-dwelling participants who underwent a comprehensive geriatric assessment at a tertiary hospital in South Korea. Sarcopenia was defined by specific cutoff values applicable to the Asian population, whereas plasma SDF-1 levels were determined using an enzyme immunoassay. RESULTS: After accounting for sex, age, and body mass index, participants with sarcopenia and low muscle mass exhibited plasma SDF-1 levels that were 21.8% and 18.3% lower than those without these conditions, respectively (P=0.008 and P=0.009, respectively). Consistently, higher plasma SDF-1 levels exhibited a significant correlation with higher skeletal muscle mass index (SMI) and gait speed (both P=0.043), and the risk of sarcopenia and low muscle mass decreased by 58% and 55% per standard deviation increase in plasma SDF-1 levels, respectively (P=0.045 and P=0.030, respectively). Furthermore, participants in the highest SDF-1 tertile exhibited significantly higher SMI compared to those in the lowest tertile (P=0.012). CONCLUSION: These findings clinically corroborate earlier experimental discoveries highlighting the muscle anabolic effects of SDF- 1 and support the potential role of circulating SDF-1 as a biomarker reflecting human muscle health in older adults.

Phase 1 trial of 4-1BB-based adoptive T-cell therapy targeting human telomerase reverse transcriptase in patients with advanced refractory solid tumors.

BACKGROUND AIMS: Human telomerase reverse transcriptase (hTERT) is an attractive target for anti-cancer therapies. We developed an effective method for generating hTERT-specific CD8+ T cells (hTERT-induced natural T cells [TERTiNTs]) using peripheral blood mononuclear cells (PBMCs) from patients with solid cancers and investigated their feasibility and safety. METHODS: This was a single-center phase 1 trial using a 3 + 3 dose escalation design to evaluate six dose levels of TERTiNTs. PBMCs from each patient were screened using an hTERT peptide panel to select those that stimulated CD8+ T cells. The four most stimulatory peptides were used to produce autologous CD8+ T cells from patients refractory or intolerant to standard therapies. Eligible patients received a single intravenous infusion of TERTiNTs at different dose levels (4 × 108 cells/m2, 8 × 108 cells/m2 and 16 × 108 cells/m2). Pre-conditioning chemotherapy, including cyclophosphamide alone or in combination with fludarabine, was administered to induce lymphodepletion. RESULTS: From January 2014 to October 2019, a total of 24 patients with a median of three prior lines of therapy were enrolled. The most common adverse events were lymphopenia (79.2%), nausea (58.3%) and neutropenia (54.2%), mostly caused by pre-conditioning chemotherapy. The TERTiNT infusion was well tolerated, and dose-limiting toxicities were not observed. None of the patients showed objective responses. Seven patients (30.4%) achieved stable disease with a median progression-free survival of 3.9 months (range, 3.2-11.3). At the highest dose level (16 × 108 cells/m2), four of five patients showed disease stabilization. CONCLUSIONS: The generation of TERTiNTs was feasible and safe and provided an interesting disease control rate in heavily pre-treated cancer patients.

Unmet Needs and Barriers in Providing Hospital Care for Older Adults: A Qualitative Study Using the Age-Friendly Health System Framework.

Purpose: This study aims to identify unmet needs and barriers for improving inpatient care for older adults at an academic hospital in Korea by using a qualitative focus group design and the Age-Friendly Health Systems (AFHS) framework. Patients and Methods: A total of 14 healthcare providers and employees participated in focus group interviews. Participants included medical doctors, registered nurses, a receptionist, a patient transporter, a pharmacist, a physical therapist, and a social worker. The data were analyzed qualitatively, as per the Consolidated Criteria for Reporting Qualitative Research guidelines. The analysis method encompassed a thematic framework analysis via the AFHS 4Ms framework, consisting of the four domains "What Matters", "Medication", "Mentation", and "Mobility". Results: Multiple barriers and unmet needs were identified using the AFHS 4Ms framework in the provision of inpatient care for older adults at the hospital. The main barriers identified in the "What matters" domain are a lack of shared decision-making and individualized care plans, as well as economic and safety-conscious preferences among some older patients. In the "Medications" domain, the main barriers to providing adequate and safe pharmacotherapy include patient and caregiver-related factors, increased complexity of medication use, and lack of institutional support systems. In the "Mentation" domain, the main issues identified are communication barriers related to patients, caregiver factors, and insufficient delirium management due to a lack of adequate processes/environments such as delirium identification. In the "Mobility" domain, the main challenges include reduced mobility and geriatric complications, unnecessary mobility restrictions, and the increased risk of falls due to lack of resources and environmental factors. Conclusion: The study highlighted the need for improvements in inpatient care for older adults at an academic hospital in Korea. Identified unmet needs and barriers can be used to guide a more patient-centered approaches for an age-friendly inpatient environment.

The Clinical Frailty Scale as a Risk Assessment Tool for Dysphagia in Older Inpatients: A Cross-Sectional Study.

BACKGROUND: Dysphagia is a common problem with potentially serious consequences including malnutrition, dehydration, pneumonia, and death. However, there are challenges in screening for dysphagia in older adults. We assessed the feasibility of using the Clinical Frailty Scale (CFS) as a risk assessment tool for dysphagia. METHODS: This cross-sectional study was conducted at a tertiary teaching hospital from November 2021 to May 2022 and included 131 older patients (age ≥65 years) admitted to acute wards. We used the Eating Assessment Tool-10 (EAT-10), which is a simple measure for identifying individuals at risk of dysphagia, to assess the relationship between EAT-10 score and frailty status as measured using the CFS. RESULTS: The mean age of the participants was 74.3±6.7 years, and 44.3% were male. Twenty-nine (22.1%) participants had an EAT-10 score ≥3. The CFS was significantly associated with an EAT-10 score ≥3 after adjusting for age and sex (odds ratio=1.48; 95% confidence interval [CI], 1.09-2.02). The CFS was able to classify the presence of an EAT-10 score ≥3 (area under the receiver operating characteristic [ROC] curve=0.650; 95% CI, 0. 544-0.756). The cutoff point for predicting an EAT-10 score ≥3 was a CFS of 5 according to the highest Youden index, with a sensitivity of 82.8% and a specificity of 46.1%. The positive and negative predictive values were 30.4% and 90.4%, respectively. CONCLUSION: The CFS can be used as a tool to screen for the risk of swallowing difficulty in older inpatients to determine clinical management encompassing drug administration routes, nutritional support, prevention of dehydration, and further evaluation of dysphagia.

Lack of association between serum myonectin levels and sarcopenia in older Asian adults.

Myonectin is a muscle-secreted factor that helps maintain homeostasis in the body by regulating several functions, including lipid metabolism. Previous studies suggested that myonectin may play a role in muscle health in an autocrine manner, but its impact on human skeletal muscle is still unclear. We aimed to investigate the relationship of serum myonectin levels with sarcopenia and related muscle parameters. We conducted a cross-sectional study of 142 older adults whose muscle mass, grip strength, gait speed, chair stands, and short physical performance battery (SPPB) were evaluated in the geriatric clinic of a tertiary medical center. Sarcopenia was defined based on Asian-specific cutoff values, and circulating myonectin levels were measured using an enzyme immunoassay. Before and after adjusting for age, sex, and body mass index, the serum myonectin level was not significantly different when the patients were stratified by status of sarcopenia, muscle mass, muscle strength, and physical performance. Furthermore, whether given as a continuous variable or divided into quartile groups, the serum myonectin level had no association with the skeletal muscle mass, grip strength, gait speed, chair stand test, or SPPB score. Our findings did not confirm the potential role of myonectin in muscle metabolism observed in experimental research. Thus, serum myonectin levels cannot predict the risk of sarcopenia in older Asian adults.

Comparative Study of the Accuracy of At-Point Clinical Frailty Scale and Morse Fall Scale in Identifying High-Risk Fall Patients among Hospitalized Adults.

BACKGROUND: Falls are a major concern among hospitalized adults, and it is essential to identify high-risk patients to prevent falls. This retrospective cohort study conducted at the Asan Medical Center, Korea, compared the screening abilities of the at-point Clinical Frailty Scale (CFS) and Morse Fall Scale (MFS) to identify patients at high risk for falls among hospitalized adults. METHODS: We assessed the records of at-point CFS, MFS, and fall incidence during hospitalization of 2,028 patients aged 18 or older included in this study. We calculated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the curve (AUC) for each tool. RESULTS: Twenty-five patients (1.23%) experienced falls during hospitalization. The mean at-point CFS score was significantly higher in those with falls than in those without falls. The mean MFS score did not differ significantly between the two groups. The optimal cutoff points for the at-point CFS and MFS scores were 5 and 45, respectively. At these cutoffs, the at-point CFS demonstrated a sensitivity of 76.0%, specificity of 54.0%, PPV of 2.0%, and NPV of 99.4%, whereas the MFS demonstrated a sensitivity of 60.0%, specificity of 68.1%, PPV of 2.2%, and NPV of 99.4%. The AUC values for the at-point CFS and MFS were 0.68 and 0.63, respectively, with no significant difference (p=0.31). CONCLUSION: The at-point CFS is a valid screening tool for assessing fall risk in hospitalized adults, as it effectively identifies fall risk with a performance similar to that of the MFS.

Korean Working Group on Sarcopenia Guideline: Expert Consensus on Sarcopenia Screening and Diagnosis by the Korean Society of Sarcopenia, the Korean Society for Bone and Mineral Research, and the Korean Geriatrics Society.

Despite the introduction of a diagnostic code and acceptance of a diagnostic process for sarcopenia as a new health technology in Korea, many practitioners remain unfamiliar with the evaluation of sarcopenia. Thus, the Korean Working Group on Sarcopenia (KWGS) developed clinical practice guidelines for the diagnosis of sarcopenia in older Korean adults. A two-phase Delphi interview comprising 19 questions was conducted with 40 expert panelists, 22 of whom participated in the first round between June and August 2022. The second round of the Delphi interview included the remaining 11 questions that were not agreed upon in the first round. The screening process for sarcopenia includes various questionnaires and examinations used in different research and clinical settings. The diagnostic process for sarcopenia was simplified by combining the steps of case finding and assessment. The Short Physical Performance Battery test was given particular emphasis owing to its multifaceted nature. Regardless of muscle mass, having low muscle strength with low physical performance is considered clinically relevant and newly defined as "functional sarcopenia." Comprehensive geriatric assessment is important for diagnosing sarcopenia. The KWGS's clinical guideline aims to facilitate the early detection of sarcopenia by allowing various screening tools to be used in a unified process and reducing confusion about which tools to use for diagnosis. This recommendation expands the conceptual definition of sarcopenia as a complex pathophysiological state in line with the concept of frailty and aims to stimulate further research on the diagnosis and management of sarcopenia in clinical settings.

Height loss as an indicator of ageing through its association with frailty and sarcopenia: An observational cohort study.

BACKGROUND: Height loss is associated with various health-related variables such as cardiovascular disease, osteoporosis, cognitive function, and mortality. We hypothesized that height loss can be used as an indicator of aging, and we assessed whether the degree of height loss for 2 years was associated with frailty and sarcopenia. METHODS: This study was based on a longitudinal cohort, the Pyeongchang Rural Area cohort. The cohort included people aged 65 years or older, ambulatory, and living at home. We divided individuals according to the ratio of height change (height change for 2 years divided by height at 2 years from baseline): HL2 (<-2%), HL1 (-2%--1%), and REF (-1%≤). We compared the frailty index, diagnosis of sarcopenia after 2 years from baseline, and the incidence of a composite outcome (mortality and institutionalization). RESULTS: In total, 59 (6.9%), 116 (13.5%), and 686 (79.7%) were included in the HL2, HL1, and REF groups, respectively. Compared with the REF group, groups HL2 and HL1 had a higher frailty index, and higher risks of sarcopenia and composite outcome. When groups HL2 and HL1 were merged, the merged group had higher frailty index (standardized B, 0.06; p = 0.049), a higher risk of sarcopenia (OR, 2.30; p = 0.006), and a higher risk of composite outcome (HR, 1.78; p = 0.017) after adjusting for age and sex. CONCLUSIONS: Individuals with greater height loss were frailer, more likely to be diagnosed with sarcopenia and had worse outcomes regardless of age and sex.

Geriatric Medicine in South Korea: A Stagnant Reality amidst an Aging Population.

In the face of an ever-increasing wave of an aging population, this paper provides an update on the current status of geriatric medicine in Korea, comparing it with global initiatives and suggesting future directions. Older adults require a multifaceted approach, addressing not only comorbidity management but also unmet complex medical needs, nutrition, and exercise to prevent functional decline. In this regard, the World Health Organization's Integrated Care for Older People guidelines underscore the importance of patient-centered primary care in preventing a decline in intrinsic capacity. Despite these societal needs and the ongoing aging process, the healthcare system in Korea has yet to show significant movement or a shift toward geriatric medicine, further complicated by the absence of a primary care system. We further explore global efforts in establishing age-integrative patient-centered medical systems in Singapore, Australia, Canada, the United Kingdom, and Japan. Additionally, we review the unmet needs and social issues that Korean society is currently facing, and local efforts by both government and a private tertiary hospital in Korea. In conclusion, considering the current situation, we propose that the framework of geriatric medicine should form the foundation of the future healthcare system.

A Comparative Study of High-Frequency Bioelectrical Impedance Analysis and Dual-Energy X-ray Absorptiometry for Estimating Body Composition.

Though bioelectrical impedance analysis (BIA) is a favorable tool for assessing body composition to estimate nutritional status and physical fitness, such as sarcopenia, there are accuracy issues. Hence, high-frequency (HF) BIA equipment uses an additional frequency of 2 and 3 MHz and has been developed as a commercial model. However, there are no studies validating the accuracy and safety of HF-BIA. Therefore, this study aims to assess the validity of HF-BIA in analyzing body composition relative to dual-energy X-ray absorptiometry (DEXA). Appendicular lean mass (ALM), fat-free mass (FFM), and percentage of body fat (PBF) were assessed by HF-BIA and DEXA in 109 individuals; 50.5% (n = 55) were males. The average age and body mass index (BMI) were 43.4 ± 14.7 years and 25.5 ± 6.7 in males and 44.9 ± 14.1 years and 24.0 ± 6.4 in females, respectively. The HF-BIA results showed a high correlation with the DEXA results for assessing ALM (standard coefficient beta (ß) ≥ 0.95), FFM (ß ≥ 0.98, coefficient of determinations (R2) ≥ 0.95), and PBF (ß ≥ 0.94, R2 ≥ 0.89). Body composition measured by HF-BIA demonstrated good agreement with DEXA in Korean adults.

At-Point Clinical Frailty Scale as a Universal Risk Tool for Older Inpatients in Acute Hospital: A Cohort Study.

Background: While the Clinical Frailty Scale (CFS) has been extensively validated for predicting health outcomes in older adults, the role of the at-point CFS at the time of examination is unclear. We aimed to examine the ability of the at-point CFS for predicting clinical outcomes of older inpatients. Methods: As a single-center and prospective cohort study, we enrolled 1,016 older adults who were 65 years or older and were admitted to one of 9 medical or surgical units from May 2021 to September 2021. The associations of the at-point CFS with outcomes of falls, delirium, pressure ulcers, 30-day unplanned readmission and/or emergency department (ED) visits, institutionalization, and a composite outcome were analyzed. Results: In the study population (n = 1,016), 26 patients had incident pressure ulcers, 6 patients had falls, 50 patients experienced delirium, and 13 patients died during hospitalization. Also, 37 patients experienced an ED visit and 22 patients had an unplanned readmission within 30 days after discharge. The composite outcome was 1.7% among patients with the CFS < 5 and 28.5% among patients with the CFS ≥ 5. The higher CFS was associated with an increased risk of a fall [odds ratio (OR) 1.74 (1.01-3.01)], pressure ulcers [OR 3.02 (2.15-4.23)], delirium [OR 2.72 (2.13-3.46)], 30-day readmission [OR 1.94 (1.44-2.62)], ED visit [OR 1.81 (1.47-2.23)], death [OR 3.27 (2.02-5.29)], and institutionalization after discharge [OR 1.88 (1.62-2.18)]. Conclusion: The at-point CFS assessed in older inpatients can screen high-risk individuals who might experience adverse geriatric conditions and in-hospital outcomes.

Operationalization of the Clinical Frailty Scale in Korean Community-Dwelling Older People.

Background: The Clinical Frailty Scale (CFS) is a simple measure of global fitness validated in various populations in real-world settings. In this study, we aimed to assess the characteristics and validities of the CFS in community-dwelling older people in Korea, with the original classification tree (oCFS) and a culturally modified tree (mCFS). Methods: The comprehensive geriatric assessment records of 1,064 individuals of the Aging Study of the Pyeongchang Rural Area were used for this study. For mCFS, we considered the dependency of the food preparations and household chores not to be deficits in the male population. The frailty index was used as a reference for construct validity. We used a composite outcome of death and institutionalization for outcome validity. Results: The correlation coefficients with frailty index were higher in mCFS (.535) than in oCFS (.468). The mean frailty index was lower in individuals reclassified by mCFS (5 to 4) than people who stayed in mCFS 5. The classification coefficient of mCFS was significantly higher than that of oCFS (p <0.001) in determining people with frailty (frailty index.25 or higher). Trends of a higher incidence of the composite outcome were observed in both higher oCFS and mCFS, in which oCFS and mCFS did not differ significantly in predicting the risk of the outcome. Conclusion: The classification tree of CFS could be culturally adopted in a community-dwelling population of Korea and considered valid in detecting the vulnerable population.

Oxaliplatin (3 months v 6 months) With 6 Months of Fluoropyrimidine as Adjuvant Therapy in Patients With Stage II/III Colon Cancer: KCSG CO09-07.

PURPOSE: The combination of oxaliplatin and fluoropyrimidine for 6 months is one of the standard options for adjuvant therapy for high-risk stage II and III colorectal cancers (CRCs). The optimal duration of oxaliplatin to diminish neurotoxicity without compromising efficacy needs to be clarified. PATIENTS AND METHODS: This open-label, randomized, phase III, noninferiority trial randomly assigned patients with high-risk stage II and III CRC to 3 and 6 months of oxaliplatin with 6 months of fluoropyrimidine groups (3- and 6-month arms, respectively). The primary end point was disease-free survival (DFS), and the noninferiority margin was a hazard ratio (HR) of 1.25. RESULTS: In total, 1,788 patients were randomly assigned to the 6-month (n = 895) and 3-month (n = 893) arms, and 83.6% in the 6-month arm and 85.7% in the 3-month arm completed the treatment. The neuropathy rates with any grade were higher in the 6-month arm than in the 3-month arm (69.5% v 58.3%; P < .0001). The 3-year DFS rates were 83.7% and 84.7% in the 6-month and 3-month arms, respectively, with an HR of 0.953 (95% CI, 0.769 to 1.180; test for noninferiority, P = .0065) within the noninferiority margin. Among patients with stage III CRC treated by capecitabine plus oxaliplatin, the 3-year DFS of the 3-month arm was noninferior as compared with that of the 6-month arm with an HR of 0.713 (95% CI, 0.530 to 0.959; P = .0009). However, among patients with high-risk stage II and stage III CRC treated by infusional fluorouracil, leucovorin, and oxaliplatin, the noninferiority of the 3-month arm compared with the 6-month arm was not proven. CONCLUSION: This study suggests that adding 3 months of oxaliplatin to 6 months of capecitabine could be considered an alternative adjuvant treatment for stage III CRC (ClinicalTrials.gov identifier: NCT01092481).