Colorectal Cancer Screening in the Elderly: Is Age Just a Number?

IntroductionColorectal cancer screening improved outcomes for patients diagnosed between the age of 45-75. Present life expectancy is beyond this limit, yet there are no guidelines for these ages. We aim to identify outcomes after screening and intervention in patients ≥75 years and correlate with frailty.Materials and methodsRecords between 2011 and 2019 were queried. Patients ≥75 screened and treated for colorectal cancer were included. Patient demographics, perioperative mortality, age at last colonoscopy and frailty score were calculated. A Modified Frailty Index from the Canadian Study of Health and Aging Frailty Index was used. A score of 1 to 11 was calculated based on patient comorbidities. The MFI was assigned from 0 to 11: 0 signified absence of frailty and 11 indicated maximum frailty.ResultsOf 179 patients were identified, 46.3% males. 171(95%) had elective and 8 (5%) had emergent surgery. The average age was 81.8 years. All colonoscopies were performed for symptoms. A modified frailty index was retrospectively calculated; 75% of patients scored between 0 and 2 and 1% scored >6.ConclusionOlder patients who underwent colonoscopy and surgery for symptomatic colon cancer had a low mortality, 2%. The average age was 6.8 years older than the recommended cutoff for colonoscopy screening. Most patients scored 0 to 2 on the modified frailty index, suggesting that not only are older patients more fit than previously thought, but also able to tolerate colorectal interventions more liberally. Utilizing frailty indices to identify screening patterns beyond 75 years of age might prove beneficial for this patient population. Further studies are recommended.     

Complication rates,failure to rescue and in-hospital mortality after cytoreductive nephrectomy in the older patients

ObjectivesHistorical data showed worse perioperative outcomes after cytoreductive nephrectomy (CN) in older patients. Additionally, the CARMENA trial questioned the survival benefit of cytoreductive CN. We reassessed complication, failure to rescue (FTR) and mortality rates after CN in a contemporary cohort of older patients with metastatic renal cell carcinoma (mRCC).Materials and MethodsFrom National Inpatient Sample (NIS) database (2008–2015), mRCC patients treated with CN were abstracted. Univariable and multivariable logistic regression models tested for the relationship between age (≤55 vs. 56–70 vs ≥71 years), Charlson Comorbidity Index (CCI) and modified Frailty Index (mFI) categories and complications, FTR and in-hospital mortality. All models were clustered, weighted and adjusted for all available patient and hospital characteristics.ResultsOf 3644 mRCC patients treated with CN, 924 (25.4%) were ≥ 71 years old, 435 (11.9%) had CCI ≥ 2 and 749 (20.6%) were frail. In multivariable logistic regression models, age ≥ 71 (odds ratio [OR] 1.4, p < .001), CCI ≥ 2 (OR 1.88, p < .001) and frail status (OR 1.91, p < .001) were independent predictors of overall complications. Age ≥ 71 was also an independent predictor of FTR (OR 2.27, p = .04), but not of in-hospital mortality. Both CCI and mFI were not significantly associated with either FTR or in-hospital mortality.ConclusionOlder patients with mRCC are more likely to experience higher rates of overall complications, FTR and in-hospital mortality following CN. These results highlight the importance of rigorous selection criteria for older surgical candidates. Moreover, timely recognition and rapid response to complications are particularly critical in this population.     

Performance of the International Myeloma Working Group myeloma frailty score among patients 75 and older

ObjectivesWe compared the performance of two frailty scoring systems in predicting survival among older patients with multiple myeloma: the International Myeloma Working Group (IMWG) frailty score (which includes age), and the Fried model for frailty (which does not).MethodsFrom 2015 to 2018, all patients aged 75 years and older presenting at our institution with a diagnosis of multiple myeloma were approached for a frailty screening assessment. We first categorized patients' frailty using the Fried model. Then, using available deficit measures, we reclassified frailty using the IMWG approach. We compared the performance of the IMWG strategy to the Fried model in terms of association with overall survival.ResultsOf the 98 (92%) patients who consented to a baseline frailty assessment, we found 57% discordance among frailty classification between the two scoring systems. Using the IMWG strategy, 9% of the cohort was “fit,” 29% “intermediate-fit,” and 62% “frail.” Using the Fried model, 29% of the cohort was “robust,” 52% “pre-frail,” and 19% “frail.” Frailty category in the Fried model was predictive of overall survival among our cohort, while frailty category in the IMWG strategy was not (log-rank p = 0.04 vs. 0.34).ConclusionAmong our cohort of older patients with myeloma (aged 75 and higher), the Fried model appears to be a better predictor of survival compared to the IMWG strategy. These results suggest that using age as a criterion to identify frailty in older patients with multiple myeloma may limit treatment options for the functionally vigorous.     

Association of frailty with 90-day postoperative mortality & geriatric comanagement among older adults with cancer

IntroductionGeriatric medical comanagement of older surgical patients with cancer is associated with lower 90-day postoperative mortality. Here, we investigate the hypothesis that this association varies on the basis of the degree of a patient's frailty.MethodsFrailty was assessed using the Memorial Sloan Kettering Frailty Index. Our hypothesis was evaluated using two approaches, both adjusted for age, sex, American Society of Anesthesiologists Physical Status, preoperative albumin, operating room duration, and estimated blood loss. A logistic regression was performed with 90-day mortality as the outcome and geriatric comanagement, continuous Memorial Sloan Kettering Frailty Index, and an interaction term between these two variables as the primary predictors. We then categorized frailty into four levels and, within each level, performed logistic regression with geriatric comanagement as the primary predictor and 90-day mortality as the outcome. Finally, we extracted the effect size and used a meta-analytic approach to test for heterogeneity.ResultsOf 1687 patients aged ≥75 years who underwent elective cancer surgery with a length of stay of ≥1 day, 931 (55%) received comanagement; 31 patients (3.3%) who received comanagement died within 90 days, compared with 72 (9.5%) who did not. Ninety-day mortality was not statistically significantly different by degree of frailty in either analysis (interaction P = 0.4; test of heterogeneity P = 0.8).ConclusionGeriatric comanagement is valuable for all older surgical patients, not just the frail, and should be provided to as large a portion of the older surgical population as possible. Further research should examine predictors of response to geriatric comanagement.     

The Surgical Apgar score combined with Comprehensive Geriatric Assessment improves short- but not long-term outcome prediction in older patients undergoing abdominal cancer surgery

Objectives

Frailty increases the risk of poor surgical outcomes in the older population. Some measurable intraoperative factors may also influence the final outcome. The Surgical Apgar Score (SAS) is a simple system predicting postoperative mortality and morbidity. However, the usefulness of the SAS remains unknown in fit and frail older patients. We aimed to test this, as well as investigate whether SAS can increase the predictive value of frailty in this group of patients.

Relationship between frailty and mortality after gastrectomy in older patients with gastric cancer

ObjectivesFrail older adults with gastric cancer are at an increased risk of poor postoperative outcomes. We assessed whether geriatric frailty assessed using the Study of Osteoporotic Fractures (SOF) index could predict post-gastrectomy mortality.Materials and methodsWe retrospectively assessed older adults (age ≥ 65 years) who underwent gastrectomy for gastric cancer between April 2012 and September 2015. Frailty status was assessed using the SOF index (range, 0–3) and categorized as robust (0), pre-frail (1), and frail (2–3). The Kaplan–Meier method and log-rank tests were used to compare survival between frailty groups. Univariate and multivariate analyses were used to identify mortality-associated risk factors.ResultsAmong 231 patients (the median age 72.04 years and 140 (60.6%) men), 138 (59.7%) were robust, 58 (25.1%) were pre-frail, and 35 (15.2%) were frail. The mortality rate was 14.5% among robust patients, 20.7% among pre-frail patients, and 20.0% among frail patients (log-rank test, P = 0.032). Frail patients had more than a 3-fold increased risk of mortality compared with robust patients (adjusted HR = 3.331; 95% CI, 1.161–9.559). Multivariate analysis revealed that the SOF index and TNM stage were associated with increased mortality.ConclusionsSOF index predicted post-gastrectomy mortality among older patients independently of age, sex, TNM stage, type of approach, gastrectomy type, and extent of lymph node dissection. SOF index may be used with ease to assess frailty status among older patients with gastric cancer in busy clinics and subgroups that may benefit from targeted frailty interventions before cancer treatments.     

Frailty and treatment decisions in older patients with vulvar cancer: A single-center cohort study

IntroductionVulvar cancer is a disease that mainly affects older women. Frailty is an important predictor of outcomes and geriatric assessment can help tailor treatment decisions and improve outcomes. This study aims to assess the prevalence of frailty in older women with vulvar cancer, and how it relates to integrated geriatric care and treatment according to the oncological guidelines.Materials and MethodsA single-center cohort study was performed, among patients 70 years and older, who were diagnosed with vulvar cancer at Leiden University Medical Center, between January 2012 and May 2020. Data on geriatric assessment, treatment decision-making and treatment-related outcomes were collected.ResultsOur study included 114 patients. Mean age was 79.7 years, and 52 patients (45.6%) were frail. Of the frail patients, 42.0% were referred to a geriatrician. In eight of these cases, the geriatrician was actively involved in weighing the benefit and harm of standard oncological treatment versus de-escalated treatment. Frailty, higher age, impairment in the somatic domain, cognitive impairment, and functional dependency were associated with referral to a geriatrician and with active involvement of a geriatrician in decision making. In 26 of frail patients (50.0%) oncological treatment was de-escalated. Frailty, higher age, impairment in the somatic domain, cognitive impairment, and functional dependency were associated with de-escalation of treatment. De-escalated treatment did not compromise survival.DiscussionFrailty is prevalent among older women with vulvar cancer and is associated with referral to a geriatrician and de-escalation of oncological treatment. While this reflects that it is deemed important to tailor treatment decision for frail patients, most frail patients are not routinely evaluated by a geriatrician. Further multidisciplinary collaboration and research is necessary to optimize tailored treatment decisions for this patient group.     

Frailty and treatment outcome in advanced gastro-oesophageal cancer: An exploratory analysis of the GO2 trial

IntroductionResearch into the optimal management of frail patients with cancer is limited and treatment decision-making in this cohort can be difficult. A number of measures have been developed to assess frailty, but few studies explore the correlation between frailty measures and cancer treatment outcomes.MethodsThis retrospective cohort study is an exploratory analysis of the GO2 randomised controlled trial. GO2 recruited both older and frail younger patients commencing first-line palliative chemotherapy for advanced gastro-oesophageal (aGO) cancer. This analysis aims to explore the correlation between baseline frailty and treatment outcome. Baseline frailty measures were derived from clinical data and included ECOG Performance Status (PS), the GO2 Frailty Score (GO2FS), Geriatric-8 (G8), Cancer and Aging Research Group (CARG) toxicity score and a ‘modified’ Rockwood Clinical Frailty Scale (mCFS). Novel patient-centred composite measure Overall Treatment Utility (OTU) was the primary endpoint. Ordinal logistic regression was undertaken to give odds ratios for poor vs good/intermediate OTU. Secondary endpoints were progression-free and overall survival. Models were adjusted for age, sex, histology, metastases, Trastuzumab and renal/hepatic function.ResultsIn GO2, 514 patients were randomised between three chemotherapy dose-levels; all of these patients were assessed for OTU and are included in this analysis. Worse GO2FS, mCFS and G8 scores all had a statistically significant association with poor (vs good/intermediate) OTU, progression and death, which persisted after adjustment. Adjusted odds ratios for poor OTU amongst those with the worst GO2FS and mCFS and best G8 scores were as follows: 1.85 (95% confidence interval [CI] 1.20–2.88) for GO2FS ≥3 (‘severely frail’), 1.72 (1.19–2.50) for mCFS 5+ (‘frail’) and 0.57 (0.32–1.00) for G8 > 14 (‘normal’). Worse ECOG PS and CARG scores did not have a statistically significant association with poor OTU/progression/death.ConclusionIn this study, frailty identified via GO2FS, mCFS and G8 conveyed a statistically significant increased risk of worse treatment outcome in older and frail younger patients with aGO cancer. Frailty assessment provides information over and above PS and should be integrated alongside routine assessments in research and clinical practice. In the absence of prospective data, frailty measures can be derived retrospectively to build the evidence base around optimal care of frailer patients.     

Robotic versus open pancreaticoduodenectomy: Is there any difference for frail patients?

BackgroundOld age and frailty are predictors of early postoperative results after pancreatic surgery. We analysed the results of robotic and open pancreatoduodenectomy in elderly and frail patients.MethodsData from the local robotic pancreatoduodenectomy database were reviewed and matched with those from open operations during the same period (2014–2020). Both old age and frailty were used to determine any correlation with postoperative outcomes. Elderly patients were defined as patients aged 70 years or more, while frailty was classified according to the validated modified Frailty Index.ResultsA total of 118 pancreatoduodenectomies were included in the analysis: 65 (55.1%) robotic and 53 (44.9%) open. More than 50% of patients were frail. Overall, 7.6% of patients experienced grade IV Clavien-Dindo complications, and 3.4% died within 90 days after surgery. Frail patients experienced a similar rate of severe complications after robotic vs. open operations (5.3 vs. 11.6; p = 0.439) but earlier refeeding (3 days vs. 4 days; p = 0.006) and earlier drain removal (6 days vs. 7 days; p = 0.046) when operated on by a robotic approach. The oncological outcomes, including limphnodes retrieval, residual disease, recurrences, and survival, were not influenced by the surgical approach. Non-elderly patients also showed more benefits with the robotic approach (lower complication index, earlier refeeding, and drain removal).ConclusionsRobotic pancreatoduodenectomy is associated with risks of major complications that are comparable to those of open operation in frail patients. Some perioperative parameters (refeeding, drain removal) seem to favour robotics in frail patients and younger patients, although at the price of longer operating times.     

Usefulness of eight screening tools for predicting frailty and postoperative short- and long-term outcomes among older patients with cancer who qualify for abdominal surgery

IntroductionThe aim of this study was to compare the ability of eight frailty screening scores to predict short- (30-day major morbidity and mortality), long-term outcomes (12-month mortality) and to compare their accuracy for predicting frailty among older patients with cancer undergoing elective abdominal surgery with curative intent.Materials and methodsConsecutive patients aged ≥70 years were enrolled prospectively. The diagnostic performance of eight screening tests were evaluated: The Vulnerable Elderly Survey (VES-13), Triage Risk Screening Tool (TRST), Geriatric 8 (G8), Groningen Frailty Index (GFI), abbreviated Comprehensive Geriatric Assessment (aCGA), Rockwood, Balducci and Fried score. Frailty was defined based on the Geriatric Assessment (GA) with two (2ID) or three impaired domains (3ID).ResultsThe study included 269 consecutive patients; median age 78 (range 70–94) years. The prevalence of frailty based on the reference GA was: 40.9% (2ID), 34.2% (3ID) and using screening tools 40–75.5%. The area under the curve (AUC) for predicting the postoperative outcome was: 0.58–0.75 (30-day morbidity), 0.54–0.71 (30-day mortality) and 0.59–0.74 (12-month mortality), respectively, being the highest for the G8. The AUC for the frailty screening tests was: 0.67–0.85 (at the 2ID) and 0.63–0.83 (at the 3ID), being the highest for the aCGA.ConclusionThe G8 was the best predictor of 30-day major morbidity, 30-day and 12-month mortality. It also had the highest sensitivity and negative predictive value in frailty screening, in case of both frailty definitions. In turn, the aCGA had the highest discriminatory ability in terms of frailty screening.     

Combination of Frailty Status and Comorbidity Score Improves the Stratification of Survival in Patients With Myelodysplastic Syndrome Owing to Good Predictive Capability for Infection-related Mortality

BackgroundWe investigated the prognostic effects of frailty and its association with comorbidity in patients with myelodysplastic syndrome (MDS).Patients and MethodsThis retrospective analysis included 118 consecutive patients diagnosed with MDS. Frailty was evaluated using the clinical frailty scale (CFS). Comorbidity was classified using the Charlson comorbidity index (CCI) and MDS comorbidity index (MDS-CI).ResultsOn multivariate analysis, CFS (≥ 5 vs. < 5; hazard ratio [HR], 3.37; P = .002), CCI (≥ 2 vs. < 2; HR, 2.59; P = .002), and Revised International Prognostic Scoring System (IPSS-R) category (HR, 2.1; P = .009) were independently predictive of overall survival (OS). One-year OS of patients with CFS ≥ 5 or CCI ≥ 2 were significantly worse compared with those with CFS < 5 or CCI < 2 (55% vs. 91%; P < .001; 46% vs. 91%; P < .001, respectively). OS was clearly stratified into 3 groups according to CFS (≥ 5 vs. < 5) and CCI (≥ 2 vs. < 2; P < .001). When comparing these 3 groups, the incidence of infection-related mortality progressively increased with CFS ≥ 5 and/or CCI ≥ 2 (P < .001). This effect was more obvious in patients with lower IPSS-R.ConclusionThe present study suggests frailty and comorbidity may be patient-related, independent predictive factors of poor prognosis. This could probably be attributed to increasing infection-related mortality with frailty and comorbidity. Combining the evaluation of frailty and comorbidity with IPSS-R might aid in more precise prediction of OS, especially in patients with low risk of MDS.     

A comparison of three different approaches to defining frailty in older patients with multiple myeloma

ObjectivesAs the aging population grows, interest in applying the concept of frailty to older adults with cancer has increased. This study examines the prevalence of frailty in older patients with multiple myeloma using three frailty models.MethodsIn this secondary analysis of a prospective cohort study, 40 adults aged ≥65 with myeloma completed the Cancer and Aging Research Group geriatric assessment within three months of initial diagnosis. Geriatric assessment data was used to categorize patients' frailty status according to three indices: The International Myeloma Working Group (IMWG) Frailty Index, the Revised Myeloma Comorbidity Index (R-MCI), and the Carolina Frailty Index (CFI). Agreement between the indices was examined using Cohen's kappa.ResultsTwenty-eight patients were classified as frail by at least one of the models. However, only slight agreement exists on the classification of frailty among the indices, with little concordance among the models (Kappa 0.03–0.12). Only three patients were categorized as frail by all three models.ConclusionIn a cohort of 40 older adults with newly diagnosed multiple myeloma, three frailty indices have differing approaches to operationalizing frailty resulting, in different patients being categorized as frail. Little agreement existed between the models. Further studies are needed to explore the utility of these models in predicting treatment toxicity and prognosis.     

The association between perioperative frailty and ability to complete a web-based geriatric assessment among older adults with cancer

IntroductionThe aim of this study was to assess the degree to which patient frailty is associated with both need for assistance and time required to complete the eRFA, a web-based GA tool.Materials and MethodsWe retrospectively identified patients who underwent surgery for cancer from 2015 to 2020, had a hospital length of stay ≥1 day, and completed the eRFA before surgery. Frailty was assessed using two methods: the MSK-FI (score 0–11) and the AGD (score 0–13). Time to complete the eRFA was automatically recorded by a web-based tool; assistance with eRFA completion was self-reported by the patient.ResultsIn total, 3456 patients were included (median age, 78 years). Overall, 58% of surveys were completed without assistance, 30% were completed with assistance, and 12% were completed by someone other than the patient. Younger age (median age: without assistance, 77 years; with assistance, 80 years; completed by someone else, 80 years) and lower frailty score (median AGD: 4, 6, and 8, respectively; median MSK-FI: 2, 3, and 3, respectively) were associated with independency (all p < 0.001). Higher frailty score was associated with longer time to complete the eRFA (all nonlinear association p < 0.001).ConclusionFrail patients are more likely to benefit from completion of GA to determine appropriate treatment. Given that not all cancer patients have a caregiver who can assist completing a digital questionnaire, innovative solutions are needed to help frail patients complete the eRFA without assistance.     

Screening for frailty among older patients with cancer using blood biomarkers of inflammation

Introduction

As frailty is associated with inflammation, biomarkers of inflammation may represent objective measures that could facilitate the identification of frailty. Glasgow prognostic score (GPS), combines C-reactive protein (CRP) and albumin, and is scored from 0 to 2 points. Higher score indicates a higher degree of inflammation.

Estimating survival time in older adults receiving chemotherapy for advanced cancer

PurposeWe determined the accuracy of oncologists' estimates of expected survival time (EST) for older adults with advanced cancer, and explored predictors of survival from a geriatric assessment (GA).MethodsPatients aged ≥65 years starting a new line of palliative chemotherapy were eligible. For each patient at enrolment, oncologists estimated EST and rated frailty (Canadian Study on Health and Aging Clinical Frailty Scale, 1 = very fit, to 7 = severely frail), and a researcher completed a GA. We anticipated estimates of EST to be: imprecise [<33% between 0.67 and 1.33 times the observed survival time (OST)]; unbiased (approximately 50% of participants living longer than their EST); and, useful for estimating individualised worst-case (10% living ≤¼ times their EST), typical (50% living half to double EST), and best-case (10% living ≥3 times EST) scenarios for survival time. Logistic regression was used to identify independent predictors of OST.ResultsThe 102 participants [median age 74 years, vulnerable to frail (4–7 on scale) 35%] had a median OST of 15 months. 30% of estimates of EST were within 0.67–1.33 times the OST. 54% of participants lived longer than their EST, 9% lived ≤1/4 of their EST and 56% lived half to double their EST. Follow-up was insufficient to observe those living ≥3 times their EST. Independent predictors of OST were frailty (HR 4.16, p < .0001) and cancer type (p = .003).ConclusionsOncologists' estimates of EST were imprecise, but unbiased and accurate for formulating scenarios for survival. A pragmatic frailty rating was identified as a potentially useful predictor of OST.     

Comparing Outcomes of Patients With Early-Stage Non–Small-Cell Lung Cancer Treated With Stereotactic Body Radiotherapy Based on Frailty Status

Introduction

Frailty of surgical patients has been associated with worse outcomes. There is limited literature discussing frailty in patients with lung cancer treated with stereotactic body radiotherapy (SBRT). This study assesses the relationship between frailty and overall survival (OS), tumor control, and toxicity in patients with early-stage non–small-cell lung cancer (NSCLC) treated with SBRT.

Frailty and clinical outcomes in critically ill patients with cancer: A cohort study

IntroductionOur aim was to assess impact of frailty on short-term clinical outcomes in critically ill patients with cancer.Materials and methodsWe conducted a cohort study at a medical and surgical intensive care unit (ICU) in Argentina. We included 269 consecutive patients, ≥18 years old, with diagnosis of cancer. We recorded demographic and clinical characteristics, Clinical Frailty Scale (CFS, ≥5 defined a patient as frail), and the number and duration of organ support therapies during ICU stay. Primary outcome was ICU and hospital mortality.ResultsMedian age 69 (range 20–90); 152 (56%) patients were male. Sixty-eight (25.2%) patients presented frailty at admission. Older adults (≥65 years old) made up 62.8% of patients. Frail patients were 69.7 years versus 64.4 years for non-frail, P = 0.007, with higher Acute Physiology and Chronic Health Evaluation II (APACHE II) 14.7 ± 7 versus 10.8 ± 6, P = 0.001 and Simplified Acute Physiology Score (SAPS II) 40.1 ± 17 versus 28.7 ± 14, P = 0.001, respectively. After adjusting by age, severity score, type of admission, and type of cancer, frailty was independently associated with hospital mortality, odds ratio (OR) 4.87 (95% confidence interval [CI], 2.19–11.19, P ≤0.001). Median ICU length of stay was five days (interquartile range [IQR] 3–7) versus six days (IQR 3.8–9), in non-frail versus frail patients, respectively (P = 0.100), and hospital stay was nine days (IQR 6–17) versus 11.5 days (IQR 7–19.5) in non-frail versus frail patients, respectively (P = 0.085).DiscussionFrailty as a medical condition was strongly associated with worse clinical outcomes among oncologic critically ill patients.     

Effect of frailty on hospital outcomes among patients with cancer in the United States: Results from the National Inpatient Sample

IntroductionTo understand the effects of frailty on hospital outcomes such as in-hospital mortality, length of stay, and healthcare cost among patients with cancer using a nationally representative database.Materials and MethodsThis study was a retrospective observational analysis of Nationwide Inpatient Sample (NIS) data collected during 2005–2014. Participants included adult patients with cancer ≥45 years identified by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. ‘Frail’ versus ‘non-frail’ hospitalizations were determined using the Johns Hopkins Adjusted Clinical Groups (ACG) frailty-defining diagnosis indicator. Main outcome measures were in-hospital mortality, hospital length of stay, and hospitalization cost. We defined prolonged length of stay as hospital stay ≥75th percentile of the study sample. Propensity score match analysis was done to examine whether frailty was associated with length of stay and in-hospital mortality.ResultsThere were 10,463,083 cancer hospitalizations during 2005–2014, of which 1,022,777 (9.8%) were frail. Patients having length of stay ≥8 days were significantly higher among frail group, compared to non-frail group (53.3% versus 25.3%, P < 0.001). Similarly, unadjusted mortality (12.0% versus 5.3%, P < 0.001) and hospitalization costs ($29,726 versus $18,595, P < 0.001) were significantly higher for frail patients. Nearly $28 billion was expended on hospitalization of frail patients with cancer during the study period. In propensity score match analysis, the odds of in-hospital mortality (odds ratio [OR], 1.54; 95% confidence interval [CI], 1.50–1.58) and length of stay (OR, 2.23; 95% CI, 2.18–2.27) were significantly greater for frail patients.DiscussionFrailty was associated with adverse hospital outcomes such as increased length of stay, mortality, and hospitalization cost among all cancer types. Our findings could be valuable for frailty-based risk stratification of patients with cancer. Concerted efforts by the physiatrists, oncologists, and surgeons towards identifying frailty and incorporating it in risk estimation measures could help in optimizing management strategies for cancer.     

Ixazomib Versus Placebo as Postinduction Maintenance Therapy in Newly Diagnosed Multiple Myeloma Patients: An Analysis by Age and Frailty Status of the TOURMALINE-MM4 Study

BackgroundThe TOURMALINE-MM4 trial demonstrated a significant and clinically meaningful progression-free survival (PFS) benefit with ixazomib versus placebo as postinduction maintenance in nontransplant, newly-diagnosed multiple myeloma patients, with a manageable and well-tolerated toxicity profile.Materials and MethodsIn this subgroup analysis, efficacy and safety were assessed by age (< 65, 65-74, and ≥ 75 years) and frailty status (fit, intermediate-fit, and frail).ResultsIn this analysis, PFS benefit with ixazomib versus placebo was seen across age subgroups, including patients aged < 65 years (hazard ratio [HR], 0.576; 95% confidence interval [CI], 0.299-1.108; P = .095), 65-74 years (HR, 0.615; 95% CI, 0.467-0.810; P < .001), and ≥ 75 years (HR, 0.740; 95% CI, 0.537-1.019; P = .064). PFS benefit was also seen across frailty subgroups, including fit (HR, 0.530; 95% CI, 0.387-0.727; P < .001), intermediate-fit (HR, 0.746; 95% CI, 0.526-1.058; P = .098), and frail (HR, 0.733; 95% CI, 0.481-1.117; P = .147) patients. With ixazomib versus placebo, rates of grade ≥ 3 treatment-emergent adverse events (TEAEs; 28-44% vs. 10-36%), serious TEAEs (15-29% vs. 3-29%), and discontinuation due to TEAEs (7-19% vs. 5-11%) were higher or similar across age and frailty subgroups, and generally somewhat higher in older age groups and intermediate-fit/frail patients in both arms. Treatment with ixazomib versus placebo did not adversely affect patient-reported quality-of-life scores across age and frailty status subgroups.ConclusionIxazomib is a feasible and effective maintenance option for prolonging PFS across this heterogeneous patient population.     

Use of comprehensive geriatric assessment (CGA) to define frailty in geriatric oncology: Searching for the best threshold. Cross-sectional study of 418 old patients with cancer evaluated in the Geriatric Frailty Clinic (G.F.C.) of Toulouse (France)

ObjectivesA consensual and operational definition of frailty is necessary in geriatric oncology. While many studies have focused on geriatric syndromes evaluated in the comprehensive geriatric assessment (CGA) to select patients at higher risk of poor outcomes, few have compared CGA data with Fried's phenotype of frailty, the most consensual measurement of frailty in geriatrics. Our objective was to determine a threshold of impaired domains evaluated in CGA associated with Frailty status.MethodsA cross-sectional study including all patients with cancer, evaluated from January 2011 to February 2016 at the Geriatric Frailty Clinic, Toulouse. A CGA was performed evaluating seven geriatric domains. Frailty was measured by Fried's phenotype to classify patients into three groups (robust/pre-frail/frail). We plotted a ROC curve to determine the threshold of impaired domains associated with frailty according to Fried.ResultsWe included 418 patients aged 82.8 years (range 66–100 years). Thirty-three patients (7.9%) were robust, 155 (37.1%) pre-frail and 230 (55%) frail. There was a significant difference in ADL, IADL, nutrition, cognition and polypharmacy between the three groups (p < .001 for each domain). Frail patients had more impaired geriatric domains on CGA than pre-frail and robust patients (respectively 4.5 ± 1.5, 2.8 ± 1.6 and 2.1 ± 1.2; p < .001). The threshold of 4 impaired geriatric domains associated with Fried's Frailty status was identified (Se 77.39%, Sp 67.55%). Area under the curve was 79.6%.ConclusionThe phenotype of frailty is associated with more impaired geriatric domains and a threshold of 4 altered domains could be used to detect frailty from CGA data.