Simplified Frailty Index Research Articles

Outcomes of Older Adults and Frail Patients Receiving Idecabtagene Vicleucel: A CIBMTR Study.

Idecabtagene vicleucel (ide-cel) is an anti-BCMA CAR-T cell therapy approved for patients with relapsed/refractory multiple myeloma (RRMM) after 2 prior lines of therapy. There is limited data on outcomes of CAR T in older adults and frail patients with RRMM. In this study, we utilized data from the Center for International Blood and Marrow Transplantation Registry to describe the safety and efficacy of ide-cel in these clinically important subgroups. An adapted version of the previously described simplified frailty index (SFI) was used to assess frailty. A total of 821 pts were followed for a median of 11.6 months (m, range, 1.1 - 26.7 m). Of these patients, 251 (30.6%) were ≥70 years of age. Older adults had higher rates of immune-effector cell associated neurotoxicity syndrome (ICANS) of any grade (37.1% vs 24.2%, p<0.01), but there were no differences in grade ≥3 ICANS or cytokine release syndrome (CRS, any grade or grade≥3). Older adults had improved progression-free survival (PFS) which remained significant in a multivariable model. There was no significant difference in treatment related mortality (TRM). Frail patients (343/766) had a higher rate of ICANS of any grade (37% versus 21.5%, p<0.01) and clinically significant infections (49.6% vs 40.9%, p=0.02), but there were no significant differences in grade ≥3 ICANS, CRS, response, PFS, overall survival or TRM.In conclusion, older adults and frail patients with RRMM had comparable efficacy to younger and non-frail patients, respectively. These patients were at higher risk of developing ICANS but had no increase in other adverse events.

Extraperitoneal Open Radical Cystectomy: A New Standard in Frail Patients with Muscle-Invasive Bladder Cancer?

Background/Objectives: Radical cystectomy (RC) represents one of the most complex and morbid surgical procedures in the field of Urology. Extraperitoneal open RC has emerged as an alternative to the traditional transperitoneal approach for the treatment of muscle-invasive bladder cancer. Frailty is one of the most important risk factors for perioperative morbidity and mortality, and this category of patients can benefit the most from the extraperitoneal approach. The purpose of this study was to evaluate the feasibility and the safety of extraperitoneal open RC in our experience; Methods: We retrospectively collected the data of 75 frail patients who underwent an extraperitoneal open RC, performed by a single experienced surgeon. We assessed their frailty status using the simplified frailty index (sFI). We recorded data regarding general characteristics, intraoperative, pathological, and postoperative complications, and mortality (within 90 days); Results: We analyzed 61 males and 14 females with an sFI equal to or higher than 3. The median age was 77 years. Fifty-one patients had an ASA score of 3 or more. Sixty procedures were with radical intention, while fifteen were palliative. Cutaneous ureterostomy was performed in 70 cases and extraperitonized ileal conduit in five cases. The median operative time was 150 min. The median blood loss was 400 mL. The median time to flatus was 2 days. The median postoperative stay was 7 days. Thirteen patients had Clavien-Dindo III or IV complications. Two patients died in first 90 days postoperatively; Conclusions: The extraperitoneal open RC in frail patients was demonstrated to be a feasible and safe alternative approach in definitive treatment or a palliative setting in our experience.

Outcomes of frail patients undergoing high-dose chemotherapy and autologous stem cell transplantation for multiple myeloma.

In patients with multiple myeloma (MM) not-eligible for autologous haematopoietic cell transplantation (autoHCT), a simplified frailty index (SFI) identifies frail patients at risk for poor outcomes, but data are limited for transplant-eligible patients. In this registry-based retrospective study, we used an adapted version of the SFI to determine the prevalence of frailty in patients ≥65 years of age with MM undergoing autoHCT. Out of 5563 patients, 37.9% of patients were classified as frail and although they had increased non-relapse mortality (NRM) and inferior overall survival, the NRM at 100 days remained low (<2%) compared with non-frail patients.

Robot-Assisted Urological Oncology Procedures, Outcomes, and Safety in Frail Patients: A Narrative Review of Available Studies.

In this study, we assess the impact of frailty on the success rate and risk of complications of robot-assisted urological procedures and introduce effective preoperative screening tools to evaluate frail patients' fitness to tolerate robot-assisted urological surgery. We performed a search of electronic databases for available studies, published up to August 2023, investigating the outcomes of robot-assisted urological oncology procedures and their safety in frail patients. Sixteen studies were ultimately selected, investigating the implications of frailty in robot-assisted radical cystectomy, robotassisted partial nephrectomy, and robot-assisted radical prostatectomy. All the studies used the Clavien-Dindo classification of complications with serious complications considered as Clavien-Dindo 3. Frail patients significantly benefit from robot-assisted urological procedures in comparison to open surgery, with lower rates of blood transfusion and a shorter length of stay. However, they also have a higher risk of postoperative complications than non-frail patients, as well as increased rates of conversion to open, total hospital costs, and in-hospital mortality after robot-assisted procedures. Robot-assisted urological procedures can improve the postoperative recovery of frail patients in comparison to open surgery. Reliable frailty indexes such as the Johns Hopkins indicator and simplified frailty index, as well as the Geriatric 8 screening tool, should be routinely used in the preoperative assessment of frail patients to optimize surgical decision-making.

Impact of Frailty on Outcomes after Chimeric Antigen Receptor T Cell Therapy for Patients with Relapsed/Refractory Multiple Myeloma

The literature is limited regarding outcomes in older adults and frail patients receiving BCMA-directed chimeric antigen receptor T cell therapy (CAR-T) for relapsed or refractory multiple myeloma. Here we describe the safety and efficacy of CAR-T in these clinically important subgroups treated in a real-world setting. Frailty was defined as a frail score ≥2 using the simplified frailty index (score based on age + Eastern Cooperative Oncology Group [ECOG] Performance Status + Hematopoietic Cell Transplantation Comorbidity Index [HCT-CI]). Of the 136 patients analyzed (age range, 41 to 81 years), 83 (61%) were considered frail at the time of CAR-T infusion. Compared to the nonfrail group, the frail group had higher proportions of patients with renal insufficiency (18% versus 6%), high-risk cytogenetics (45% versus 35%), extramedullary disease (51% versus 43%), and ECOG Performance Status ≥2 (18% versus 2%), and worse HCT-CI (3 versus 1). Although patients in the frail group had a higher incidence of immune effector cell-associated neurotoxicity syndrome (ICANS) (39% versus 17%), the incidences of all- grade cytokine release syndrome (CRS), as well as high-grade CRS and ICANS, were similar in the 2 groups. With a median follow-up of 7 months, the median progression-free survival was 6.9 months in the frail group versus 11.1 months in the nonfrail group (P = .028). The median overall survival was 14 months in the frail group and was not reached in the nonfrail group (P = .025). This study highlights the tolerable safety and reasonable efficacy of CAR-T for frail myeloma patients in a real-world practice. Although the frail patients did not experience any excessive high-grade toxicities, they did have inferior efficacy outcomes.

Impact of Frailty on Outcomes after CAR T-Cell Therapy for Patients with Relapsed/Refractory Multiple Myeloma

Introduction: Multiple myeloma (MM) is a disease of the elderly with a median age of 69 years at diagnosis. In addition to advanced age, many of these patients are frail with pre-existing comorbidities and have been historically excluded from clinical trials evaluating chimeric antigen receptor (CAR) T-cell therapy for relapsed refractory (RR) MM. It has been shown that chronologic age alone should not be a barrier towards effective treatment modalities including stem cell transplant and CAR T and that instead of age, frailty scores should be incorporated into CAR T screening and eligibility assessments. As there is limited literature on safety and efficacy of CAR T-cell therapy in frail patients, we conducted a multi-center retrospective study to evaluate clinical characteristics and outcomes of frail patients with RRMM who received standard of care CAR T-cell therapy in real-world practice. Methods: Three U.S. academic medical centers contributed data which included patients with RRMM who had received idecabtagene vicleucel (ide-cel) between 8/30/2021 and 05/31/2023. Frailty was defined using the simplified frailty index by Facon et al (score based on age + ECOG performance status + comorbidity index; frail = score ≥2). Descriptive statistics were used to analyze clinical characteristics such as age, performance status, and comorbidities. Response outcomes were evaluated using IMWG criteria. Adverse events were graded based on the ASTCT and CTCAE v5.0 criteria. Key data-points included incidence and severity of cytokine release syndrome (CRS), immune effector cell associated neurotoxicity syndrome (ICANS), infections, treatment-related mortality (TRM), overall response rates (ORR), partial response (PR), very good partial response (VGPR), complete response (CR), progression-free survival (PFS), and overall survival (OS). Results: Of the 104 patients analyzed (age range 41-81), 70 (67%) were considered frail at the time of CAR T-cell infusion. The frail group had a high proportion of patients with renal insufficiency (19% vs 6%), high-risk cytogenetics (46% vs 36%), extramedullary disease (54% vs 47%), performance status ≥2 (20% vs 3%), and worse comorbidity index (median 3 vs 1) but were otherwise similar to the non-frail group (Table 1). While patients in the frail group experienced less CRS (73% vs 88%) and more ICANS (34% vs 18%) when compared to the non-frail group, incidence of grade 3+ CRS and ICANS were similar between the two groups. Rates of infection were also similar between the groups with nearly one-third of the patients experiencing an infection within 6 months post CAR T. With a median follow up of 8 months, best ORR was 83% (37% sCR/CR, 30% VGPR, 16% PR) in the frail group vs 97% (53% sCR/CR, 35% VGPR, 9% PR) in the non-frail group. Median PFS was 6.6 months in the frail group vs 11 months (p=0.062) in non-frail group. Median OS was 14.4 months in the frail group and was not reached (p=0.086) in the non-frail group (Figure 1). TRM was observed in 3 (4%) patients in the frail group. There was no treatment related mortality observed in the non-frail group. Conclusion: A majority of patients treated with standard of care ide-cel for RRMM in this real-world experience were frail by simplified frailty index. While these patients had worse performance status and higher comorbidity burden at the time of CAR T infusion, they did not experience any excessive high-grade toxicities including TRM. When compared to the non-frail group, frail patients had numerically inferior but statistically similar depth and duration of response. This study supports the tolerable safety and reasonable efficacy of CAR T-cell therapy for frail MM patients in a real-world practice and highlights the need to study outcomes in this patient population in larger registry-based data as well as clinical trials.

A simplified frailty index and nomogram to predict the postoperative complications and survival in older patients with upper urinary tract urothelial carcinoma.

This study was designed to investigate the clinical value of a simplified five-item frailty index (sFI) for predicting short- and long-term outcomes in older patients with upper urinary tract urothelial carcinoma (UTUC) patients after radical nephroureterectomy (RNU). This retrospective study included 333 patients (aged ≥65 years) with UTUC. Patients were classified into five groups: 0, 1, 2, 3, and 3+, according to sFI score. The variable importance and minimum depth methods were used to screen for significant variables, and univariable and multivariable logistic regression models applied to investigated the relationships between significant variables and postoperative complications. Survival differences between groups were analyzed using Kaplan-Meier plots and log-rank tests. Cox proportional hazards regression was used to evaluate risk factors associated with overall survival (OS) and cancer-specific survival (CSS). Further, we developed a nomogram based on clinicopathological features and the sFI. The area under the curve (AUC), Harrel's concordance index (C-index), calibration curve, and decision curve analysis (DCA) were used to evaluate the nomogram. Of 333 cases identified, 31.2% experienced a Clavien-Dindo grade of 2 or greater complication. Random forest-logistic regression modeling showed that sFI significantly influenced the incidence of postoperative complications in older patients (AUC= 0.756). Compared with patients with low sFI score, those with high sFI scores had significantly lower OS and CSS (p < 0.001). Across all patients, the random survival forest-Cox regression model revealed that sFI score was an independent prognostic factor for OS and CSS, with AUC values of 0.815 and 0.823 for predicting 3-year OS and CSS, respectively. The nomogram developed was clinically valuable and had good ability to discriminate abilities for high-risk patients. Further, we developed a survival risk classification system that divided all patients into high-, moderate-, and low-risk groups based on total nomogram points for each patient. A simple five-item frailty index may be considered a prognostic factor for the prognosis and postoperative complications of UTUC following RNU. By using this predictive model, clinicians may increase their accuracy in predicting complications and prognosis and improve preoperative decision-making.

P-116 The simplified frailty index (S-FI) identifies a less vulnerable population of frail patients than patients who are defined frail using the International Myeloma working Group Frailty index (IMWG-FI)

P-116 The simplified frailty index (S-FI) identifies a less vulnerable population of frail patients than patients who are defined frail using the International Myeloma working Group Frailty index (IMWG-FI)

Utilizing a two-step frailty assessment strategy in older adults with multiple myeloma (MM): A decision curve analysis.

8061 Background: The International Myeloma Working Group Frailty Index (IMWG-FI) has been shown to predict risk of toxicity and mortality in older adults with MM (Palumbo et al., Blood 2015). However, IMWG-FI requires a geriatric assessment (GA) that is not routinely done in clinical practice due to time constraints. A simplified frailty index (SFI; Facon et al., Leukemia 2020) has been proposed as an alternative using ECOG PS as a proxy to functional status. We previously reported a moderate concordance between these two frailty indices (Kappa statistic 0.50; Gahagan et al., ASH 2022). Here, we examined if SFI can be utilized as a screening tool to identify patients who would benefit from a formal GA and frailty assessment. We hypothesized that a two-step approach would minimize the need for unnecessary GAs, while saving time in clinical practice. Methods: For this analysis, we included patients ≥50yo with newly diagnosed (ND) or Relapsed/Refractory (RR)-MM at a single institution initiating a new treatment regimen (1st to 6th line) who are enrolled in a prospective registry (NCT05556928). All patients underwent a GA prior to a new line of therapy. ECOG PS and comorbidities were abstracted from medical records. We calculated IMWG-FI and SFI using published methods. Sensitivity, specificity along with their 95% CI were calculated for both SFI and IMWG-FI, using published SFI cutpoints. Lastly, we used decision curve analysis (DCA) as described by Vickers et al. to calculate the benefit of frailty screening using SFI for detection of non-frail patients and avoiding unnecessary GAs. We assumed that reasonable threshold probabilities were 0.25 and 0.33 respectively indicating that missing an unfit patient was 3 and 2 times worse than exposing a fit patient to an unnecessary GA (odds of 1:3 and 1:2 respectively). We quantified the net benefit (NB) of this two-step frailty assessment versus GA-for-all in terms of net reduction in unnecessary GAs. Results: A total of 146 adults with MM (49 ND-MM, 51 pre-transplant, and 46 RR-MM) starting a new line of therapy between 8/2020-1/2022 were included in this study. The median age was 62 (IQR 57-70) with 53% males and 36% blacks. The distribution by IWMG-FI was 43% fit, 32% intermediate-fit, and 25% frail. Using SFI, 32% of patients were frail. Using a cutpoint of ≥2, SFI as a screening tool had a sensitivity of 89.2% (95% CI 75-96%) and a specificity of 65% (95% CI 56% to 73%). DCA showed that selecting candidates for GA based on a two-step strategy (SFI followed by IMWG-FI) led to an absolute 40-45% reduction in the number of unnecessary GAs without missing any frail patients. Conclusions: Our results suggest that using a two-step frailty assessment strategy of SFI as a screening tool followed by confirmation with IMWG-FI reduces the need for unnecessary GAs by 40-45% and may be more suitable for integration in busy oncology practice.

Evaluation of a commonly used tool: Does the 5-item frailty index predict phenotypic frailty?

BackgroundThe simplified frailty index (sFI) is a commonly used instrument to estimate postoperative risk, but its correlation with phenotypic frailty has been questioned. This study evaluates the relationship between sFI and phenotypic frailty, as measured by the Sinai Abbreviated Geriatric Evaluation (SAGE). MethodsCharts were retrospectively reviewed from patients ≥75 years old who underwent surgery between 2012–2022. The sFI score was calculated by adding 1 point for hypertension, COPD, congestive heart failure, functional dependence, and diabetes (score 0–5). SAGE was calculated by adding 1 point for normal gait speed, normal Mini-Cog©, and independent activities of daily living (ADL) (0–3). Spearman rank correlation was used to test the relationship between sFI and SAGE. SAGE components were used as binary-dependent outcomes in covariate-adjusted logistic regression modeling to evaluate associations with sFI scores while adjusting for potential confounders. Results334 patients were assessed, with a mean age of 84.0. SAGE and sFI scores were significantly associated, with a modest inverse relationship (r=-0.24, p<0.0001). Each 1-point increase in sFI score was associated with increased odds of ADL deficit (OR 2.3, 95%CI [1.5–3.8], p<0.0001) and abnormal gait speed (OR 1.9, 95%CI 1.2–3.0, p<0.01). The sFI score was not associated with deficits in the Mini-Cog (OR 1.5, 95%CI [0.96–2.3], p=0.07). ConclusionHigher sFI was significantly associated with increased phenotypic frailty, particularly with the loss of physical condition and function but not associated with cognitive deficit. Therefore, sFI may not be an appropriate tool to estimate postoperative complications related to cognition, such as delirium risk.

MP64-06 ROLE OF INFLAMMATORY MARKERS AND FRAILTY INDEX AS PREDICTORS OF ADVERSE PATHOLOGICAL STAGE IN PATIENTS WITH KIDNEY CANCER: a MULTICENTER ANALYSIS

You have accessJournal of UrologyCME1 Apr 2023MP64-06 ROLE OF INFLAMMATORY MARKERS AND FRAILTY INDEX AS PREDICTORS OF ADVERSE PATHOLOGICAL STAGE IN PATIENTS WITH KIDNEY CANCER: a MULTICENTER ANALYSIS Cosimo DE Nunzio, Gabriele Tuderti, Antonio Luigi Pastore, Yazan AL Sahli, Antonio Carbone, Andrea Tubaro, Riccardo Lombardo, Elisa Mancini, Giorgio Guarnotta, Simone Rocco Flammia, Antonio Tufano, Costantino Leonardo, Andrea Cantiani, Stefano Signore, Andrea Fuschi, Antonio Nacchia, Antonio Cicione, Riccardo Mastroianni, Umberto Anceschi, Giuseppe Simone, Aldo Brassetti, and Andrea Tubaro Cosimo DE NunzioCosimo DE Nunzio More articles by this author , Gabriele TudertiGabriele Tuderti More articles by this author , Antonio Luigi PastoreAntonio Luigi Pastore More articles by this author , Yazan AL SahliYazan AL Sahli More articles by this author , Antonio CarboneAntonio Carbone More articles by this author , Andrea TubaroAndrea Tubaro More articles by this author , Riccardo LombardoRiccardo Lombardo More articles by this author , Elisa ManciniElisa Mancini More articles by this author , Giorgio GuarnottaGiorgio Guarnotta More articles by this author , Simone Rocco FlammiaSimone Rocco Flammia More articles by this author , Antonio TufanoAntonio Tufano More articles by this author , Costantino LeonardoCostantino Leonardo More articles by this author , Andrea CantianiAndrea Cantiani More articles by this author , Stefano SignoreStefano Signore More articles by this author , Andrea FuschiAndrea Fuschi More articles by this author , Antonio NacchiaAntonio Nacchia More articles by this author , Antonio CicioneAntonio Cicione More articles by this author , Riccardo MastroianniRiccardo Mastroianni More articles by this author , Umberto AnceschiUmberto Anceschi More articles by this author , Giuseppe SimoneGiuseppe Simone More articles by this author , Aldo BrassettiAldo Brassetti More articles by this author , and Andrea TubaroAndrea Tubaro More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003322.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: The purpose of this study was to assess patient frailty and inflammatory state as predictors of adverse pathological outcomes after renal cancer surgery. METHODS: We performed an analysis of prospectively collected data of consecutive patients undergoing nephrectomy or patrial nephrectomy in 5 primary care Italian urology centers. Charlson comorbidity score and Frailty index was measured using a simplified frailty index (sFI) with a 5-item score including: (1) diabetes mellitus; (2) functional status; (3) chronic obstructive pulmonary disease; (4) congestive cardiac failure; and (5) hypertension, with a maximum 5-item score meaning high level of frailty. Inflammatory status was evaluated with neutrophil/lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), fibrinogen and albumin levels. Binary logistic regression analysis was used to assess the risk of advanced pathological stage. RESULTS: Two hundred and sixty-two patients were enrolled. Overall, 75/262 (29%) presented a sFI score ≥3 and 24/262 (9%) presented advanced disease (≥3a). sFI ≥3 (OR: 2,88; 95% CI: 1,22-6,82; p=0,016), Charlson comorbidity index OR=1,24; 95% CI: 1,03-1,51; p=0,024), ASA score (OR: 3,22; 95% CI: 1,72-6,06; p=0,001), fibrinogen levels (OR: 1,01; 95% CI 1,00.1,01; p=0,002) and albumin levels (OR=0,80; 95% CI: 0,69-0,93; p=0,003) were predictors of adverse pathological outcomes. NLR and MLR were not predictors of adverse pathological outcomes. CONCLUSIONS: In patients undergoing surgery for renal cancer, frailty index, inflammatory mediators and comorbidities are predictors of adverse pathological outcomes. Further studies should assess their role in clinical practice and in predictive models. Source of Funding: No one © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e883 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Cosimo DE Nunzio More articles by this author Gabriele Tuderti More articles by this author Antonio Luigi Pastore More articles by this author Yazan AL Sahli More articles by this author Antonio Carbone More articles by this author Andrea Tubaro More articles by this author Riccardo Lombardo More articles by this author Elisa Mancini More articles by this author Giorgio Guarnotta More articles by this author Simone Rocco Flammia More articles by this author Antonio Tufano More articles by this author Costantino Leonardo More articles by this author Andrea Cantiani More articles by this author Stefano Signore More articles by this author Andrea Fuschi More articles by this author Antonio Nacchia More articles by this author Antonio Cicione More articles by this author Riccardo Mastroianni More articles by this author Umberto Anceschi More articles by this author Giuseppe Simone More articles by this author Aldo Brassetti More articles by this author Andrea Tubaro More articles by this author Expand All Advertisement PDF downloadLoading ...

Evaluating Concordance between International Myeloma Working Group (IMWG) and Simplified Frailty Index (SFI) Among Older Adults with Multiple Myeloma (MM)

Introduction: Despite significant advances in therapeutics, older adults with MM are at increased risk of treatment related toxicity and mortality. Frailty is an aging-associated state of cumulative decline in many physiological systems, resulting in diminished resistance to stressors, including cancer therapy. In 2015, the International Myeloma Working Group (IMWG) developed a geriatric assessment (GA) based frailty index (IMWG-FI) using age, comorbidities, and physical function (instrumental activities of daily living, IADL; activities of daily living, ADL) to predict risk of toxicity and mortality among older adults with MM (Palumbo, et al., Blood 2015). However, GA is not routinely incorporated in clinical practice and a simplified frailty index (SFI; Facon et al Leukemia 2020) has been proposed as an alternative to using ECOG performance status (ECOG PS) as a proxy for physical function (IADL/ADL). However, the concordance between IMWG-FI and SFI remains relatively unknown, as well as their predictive ability in clinical practice, particularly among patients with relapsed, refractory multiple myeloma (RR-MM). Our goal was to describe the prevalence of frailty using IMWG-FI and SFI as well as evaluate their concordance among patients with newly-diagnosed (ND) and RR-MM. Methods: The Cancer and Aging Resilience Evaluation in Hematologic Malignancies (CARE-Heme) Registry is an ongoing prospective registry enrolling adults ≥50 years of age with a diagnosis of a hematologic malignancy undergoing treatment at a single institution. For this analysis, we included patients ≥50yo with ND- or RR-MM initiating a new treatment regimen (ranging from first to sixth line of treatment). All of the patients included in this study underwent a comprehensive GA prior to beginning a new line of therapy or stem cell transplant. We abstracted physician reported ECOG PS and comorbidities by reviewing medical records. We calculated IMWG frailty score as well as SFI using published methods. Each patient was categorized into frail/non-frail using the IMWG frailty score (fit, intermediate-fit, frail; collapsing fit/intermediate fit into the non-frail category) and the simplified frailty score (non-frail, frail) using published cutoffs. We measured the agreement between the total frailty scores using Spearman Correlation Coefficient and the frail/non-frail categorization using the Kappa statistic. Relevant treatment outcomes including progression-free survival, overall survival, and grade 2-5 toxicities (both hematologic and non-hematologic) were recorded until disease progression, death, or 6 cycles of treatment were completed. Results: A total of 146 adults with MM (49 ND-MM, 51 pre-transplant, and 46 RR-MM) starting a new line of therapy or ASCT between 8/2020 to 1/2022 were included in this study. The median age was 62 (IQR 57-70) with 53% males and 36% blacks. Most patients had IgG isotype (64%) with International Staging System (ISS) stage III disease (38%) whereas 30% patients had high risk cytogenetics. The distribution by IWMG Frailty category was as follows: 43% fit, 32% intermediate-fit, and 25% frail. Using SFI, 32% of patients were characterized as frail and 68% were characterized as non-frail (Figure 1). Although, the frailty scores were well correlated with each other (Spearman rho 0.67, p value <.001), the agreement between SFI and IMWG-FI in terms of frailty categorization was moderate (Kappa statistic 0.50); 79% of patients were classified in the same frailty group, however about 21% of patients were characterized in different frailty categories using the two scales (Table 1). SFI over-estimated frailty in about 14% of patients. There was very little agreement between a patient-reported vs physician rated ECOG-PS (Kappa statistic 0.13). The discordance between the two FI worsened if a patient reported version of ECOG PS (Kappa statistic 0.30) was used. Conclusions: Among older adults with MM, the prevalence of frailty ranged 25% by IMWG-FI to 32% by SFI. There was only a modest agreement between SFI and IMWG FI, which was worse when using patient reported version of ECOG PS. Studies comparing outcomes across the two frailty indices should take into account the potential for misclassification bias. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Variable Frailty Categorization Among Real-World Patient with Multiple Myeloma: A Prospective Cohort Study (MFRAIL)

Introduction Multiple Myeloma (MM) is a non-curable cancer of older adults. Frailty has emerged as one important high-risk factor which confers a poor prognosis with reduced progression free survival, increased toxicity, higher rates of drug discontinuation and worse overall survival. Several tools have emerged for evaluation of frailty in MM in recent years. These include non-cancer specific geriatric assessment tools such as the Fried frailty index or more specific MM tools such as the International Myeloma Working Group (IMWG) frailty index, simplified frailty index or the Mayo frailty index. Uptake of these measures across clinical settings has been variable, leading to a gap in knowledge about the prevalence of geriatric impairments among MM patients as well as the proportion of patients classified as frail using these different scoring systems. The MFRAIL study is an ongoing prospective, multicentre study evaluating the association of different frailty assessment tools at baseline and longitudinally over time with clinical outcomes. In this abstract we present an interim analysis after at least 50% of patients have been enrolled. We describe baseline characteristics from the initial 57 patients enrolled into the study with the specific objective of 1) to report the prevalence of geriatric impairments among MM patients prior to therapy initiation 2) characterize the proportion of patients classified as frail using different frailty assessment tools. Methods The MFRAIL is an ongoing, prospective pilot cohort study being conducted at three sites within Ontario, Canada which was initiated in August 2021. Multiple myeloma patients aged >18 initiating a new line of therapy are enrolled in the preceding six weeks. Demographic and MM-specific factors are collected at baseline and at 12 months following treatment along with MM response criteria, toxicity and health care utilization. Additional collected measures include: comorbidities, physical performance measures (NIH 4 meter walk test and grip strength), cognition, patient reported outcome of quality of life and depression. Frailty assessment tools measured include the IMWG frailty index (Palumbo et al. Blood 2015), simplified frailty index (Facon et al. Leukemia 2020), Mayo frailty index (Milani et al. AJH 2016) and the Fried frailty index (modified from Fried et al. J Gerontol A Biol Sci Med Sci 2001). Results A total of 57 patients were enrolled in the study (data cut off June 1/2022) with baseline characteristics summarized in Table 1. The median age of the patients was 71 (range 47-93) with 61% males. A total of 26% and 35% of the patients had an ECOG and CCI status of 2 or higher, respectively. Polypharmacy was common with over 50% of the patients being prescribed five or more medications at baseline. Geriatric impairments were common with over 1/3 of the patients reporting at least one deficit in ADLs or IADLs. Additionally, cognitive impairment was present in 19.3% of the patients. With regards to treatment details, 61.4% of the enrolled patients received first line treatment (ASCT eligible 34.3%, ASCT ineligible 65.7%), 26.3% second line and the remainder third line and beyond. Immunomodulatory-based treatments were the most common with 57.8% of the patients utilizing these agents. Empiric dose reduction outside the product monograph was observed in 17.5% of the patients with the majority of dose reductions (80%) done for agents other than dexamethasone alone among those patients. The prevalence of frailty in our cohort ranged from 12.3% (Fried frailty index), 17.5% (Mayo frailty index), 38.6% (IMWG frailty index) to 52.6% (simplified frailty score). Similarly, the number of patients classified as fit/robust also varied ranging from 15.8% (Mayo frailty index), 25.3% (fried frailty index), 33.3% (IMWG frailty index) and 47.3% (simplified frailty score). Conclusion Impairments in geriatric domain are common among real-world patients with MM emphasizing the need to incorporate these assessments in routine clinical practise. Additionally, prevalence of patients classified as frail versus fit varies depending upon the assessment tool utilized with no uniform definition of frailty in routine clinical practise. Further work is needed in both evaluating and standardizing frailty assessment tools in different clinical settings and with different therapeutic modalities to further optimize outcomes in this high-risk patient subgroup. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Pre-treatment neutrophil to lymphocyte ratio as a biomarker of frailty and predictor of survival among older adults with multiple myeloma

IntroductionNeutrophil to Lymphocyte Ratio (NLR) combines a marker of inflammation and reduced cell turnover to reflect age related alterations in the immune system. Whether NLR can serve as a biomarker of frailty and predict survival among older adults with Multiple Myeloma (MM) is unknown. Materials and methodsWe used an electronic health record-derived database to identify older adults (age ≥ 60y) with incident MM diagnosed between 1/2011 and 2/2020, with known pre-treatment absolute neutrophil and lymphocyte count up to 90 days before the start of therapy. The calculated NLR values were stratified into quartiles (Q1-Q4). We constructed a previously validated, simplified frailty index combining age, comorbidity and ECOG performance status. We measured the association between NLR quartiles and this frailty index using a logistic regression, adjusted for age, sex and race/ethnicity. We used Kaplan Meier methods and multivariable Cox regression to assess the impact of NLR on overall survival adjusting for potential confounders. ResultsWe identified 1729 older adults with newly diagnosed MM, at a median age of 73y (IQR: 67-78y). The median NLR was 2.13 (IQR: 1.44 to 3.31). Of the 1135 evaluable patients, 55% met criteria for frailty. Multivariable analysis revealed a 2.1-fold higher odds of frailty (95%CI = 1.42–3.10, p < 0.001) for patients in the NLR Q4 group vs. NLR Q1 group. In a multivariable analysis, adjusting for age, sex, race/ethnicity, M-protein type, stage, high risk cytogenetics, baseline creatinine, LDH and type of first line therapy, patients in NLR Q4 group had a 1.51 times increased hazards of death (95%CI = 1.15–1.98, p 0.002) when compared to those in NLR Q1 group. ConclusionNLR, a readily available laboratory biomarker, is associated with frailty measured using a simplified frailty index as well as inferior overall survival among older adults with MM. Future studies should explore its value as a screening tool to identify frail older adults with MM.

A Simplified Frailty Index Predicts Mortality in Older Adults in Beijing.

ObjectiveThe comprehensive geriatric assessment (CGA) is an integral tool used to identify vulnerable older adults in need of individualized plans to delay the course of diseases and monitor treatment outcomes. We previously developed and validated a 68-item frailty index (FI) based on the CGA in a large, older, Chinese population. However, substantial time is needed to evaluate the 68 items. Therefore, we aimed to develop and validate a simplified FI for use in Chinese older population.DesignLongitudinal study.Setting and ParticipantsData were drawn from the Beijing Longitudinal Study of Aging. The study was conducted in 2004 with 1808 participants evaluated using the CGA and was followed-up for 13 years. Mortality was recorded at 3, 5, 8, 10, and 13 years intervals.Measures27-Item, 50-item, and 68-item frailty indices were investigated. A Cox proportional hazards model and area under the curve of the receiver operating characteristic (AUC-ROC) were calculated to compare mortality predictions.ResultsThe FI was positively correlated with age in males (r = 0.174, P <0.001) and females (r = 0.270, P <0.001). The mean baseline FI was 0.225 ± 0.085 (range: 0.04–0.56) as evaluated by the 27-item FI, 0.181 ± 0.117 (range: 0.02–0.62) by the 50-item FI, and 0.167 ± 0.101 (range: 0.02–0.59) by the 68-item FI. Cox regression models showed that mortality was significantly higher in frail people than in non-frail people for all 3 indices (p<0.001). The AUCs of the 68-item FI, 50-item FI, and 27-item FI for predicting mortality were 0.720, 0.717, and 0.677, respectively (p<0.001).ConclusionThe 27-item FI is reasonable to expect that the AUC of the indices with the higher items number is inferior to the performance of the indices with higher number of items (FI50 and FI68). But 27-item maybe used as a tool to identify frail older adults and predict mortality in clinical and primary care practices in China.

Frailty as a Predictor of Adverse Outcomes After Peripheral Vascular Surgery in Patients With End-Stage Renal Disease.

Frailty and end-stage renal disease (ESRD) are each independently associated with adverse outcomes in patients who undergo lower extremity vascular bypass operations (LEOs). It is not known whether frailty imparts additional risk to patients with ESRD having LEO. The study was a retrospective cohort study of 29203 patients without ESRD and 1718 with ESRD who had LEO surgery between the years 2014 and 2018 extracted from the American College of Surgeons National Surgical Quality Improvement Program database. Preoperative frailty was assessed using a simplified frailty index based on a history of diabetes, heart failure, chronic obstructive pulmonary disease, hypertension, and functional status. Adverse outcomes measured were 30-day mortality, surgical complications, reoperation, length of stay, readmission, discharge destination, and any ("composite") adverse outcome. Odds ratios (ORs) for adverse outcomes were calculated with logistic regression. Among patients with ESRD, the OR for having the composite adverse outcome was greater for frailty than for any of the other preoperative risk factors studied (OR 2.191, CI 1.569-3.061, P < .001). Adverse outcomes occurred in 84.3% of frail patients with ESRD, but in only 39.6% of the non-frail patients without ESRD. Frailty imparts additional risk for adverse outcomes to patients with ESRD undergoing LEO.

Frailty is a stronger predictor than age for postoperative morbidity in Crohn’s disease

BackgroundPatients with Crohn’s disease are particularly susceptible to preoperative frailty owing to the chronic nature of the illness and immunosuppressive therapy. The hypothesis in this study was that frailty would have a greater impact on postoperative outcome than age in older individuals with Crohn’s disease. MethodsData were obtained from the National Surgical Quality Improvement Program (NSQIP) from the years 2012 to 2018. Patients with Crohn’s disease who underwent a bowel resection were identified from diagnostic and procedure codes. Frailty was assessed using the 5-point Simplified Frailty Index (0–not frail, 5–most frail). Age was defined as an ordinal variable with 3 age ranges (18–64, 65–79, >80 years). Aggregate morbidity was classified according to the standard NSQIP definitions. Simplified Frailty Index was evaluated as a potential predictor of morbidity and mortality using covariate-adjusted logistic regression modeling. ResultsA total of 9,023 patients underwent bowel resection for Crohn’s disease during the study period. Patient Simplified Frailty Index ranged from 0 to 3 (Simplified Frailty Index = 0, 82%; 1, 15%; 2, 2.5%; 3, 0.1%), and higher Simplified Frailty Index was associated with increased age (P < .01). In multivariate regression, a Simplified Frailty Index was significantly associated with postoperative morbidity (Simplified Frailty Index ≥ 2: odds ratio = 2.59, 95% confidence interval [1.84–3.63], P < .0001). In contrast, age was not found to be a significant predictor of morbidity when adjusted for Simplified Frailty Index and other covariates (P > .05). ConclusionFrailty is a stronger predictor than age for morbidity in Crohn’s-related bowel resection. Functional assessments and vulnerability screening should be used to determine surgical candidacy rather than age alone.

Frailty is a predictor of moderate to severe pain after robot-assisted laparoscopic prostatectomy: A case-control study (FRAP study).

ObjectiveTo investigate the association of pain with frailty in patients with localized prostate cancer (PC) who underwent robot‐assisted laparoscopic radical prostatectomy (RARP).Materials and MethodsBetween January 2017 and June 2019, we prospectively evaluated the geriatric 8 (G8) score, simplified frailty index (sFI), and numerical rating scale (NRS) of 154 patients with localized PC who underwent RARP at our institution. NRS was measured on preoperative day 0, postoperative days 1, 2, 3, and at discharge. Moderate to severe pain was defined as NRS ≥ 5, whereas frailty was defined as G8 ≤ 14. The primary objectives of this study were to investigate the effects of moderate to severe pain (NRS ≥ 5) on frailty, postoperative complications, and the use of analgesics after RARP. Our secondary objectives were the effect of frailty on postoperative complications and the use of analgesics.ResultsThe median age of participants was 69 years. Of 154 patients, 37 (24%) and 61 (40%) were classified to have NRS ≥ 5 and G8 ≤ 14, respectively. Patients with NRS > 5 presented significantly association with G8 < 14, whereas they did not show the association with sFI, complication, or analgesics. Multivariate logistic regression analysis showed that G8 ≤ 14 was significantly associated with NRS ≥ 5. Frailty was not significantly associated with postoperative complications and analgesics.ConclusionsFrailty was significantly associated with moderate to severe pain after RARP, and might be a potential predictor of postoperative pain. Frail patients require individual care to avoid painful experiences.

MP61-14 READMISSION RATES AND THEIR PREDICTORS AFTER ROBOTIC AND OPEN RADICAL CYSTECTOMY

INTRODUCTION AND OBJECTIVE: Radical cystectomy (RC) remains a surgery that has significant perioperative complication rates. Robot-assisted RC (RARC) was envisaged as a technique allowing for lower complication rates and readmissions when compared to open cystectomy (OC) and retrospective studies support this. We evaluated readmission rates at 90 days and 1 year following RC in patients from the RAZOR trial; a multicenter, open-label non-inferiority phase III randomized trial comparing RARC to OC. METHODS: The per-protocol population of the RAZOR trial was used for analysis. Readmission rates at 90 days and 1 year were tabulated using the RAZOR database. Frailty was evaluated by the validated simplified frailty index (sFI) (ECOG≥2, history of diabetes mellitus, chronic obstructive pulmonary disease, congestive cardiac failure, and hypertension requiring treatment). Multivariable logistic regression analysis was conducted to identify factors predicting readmission at both time points postoperatively. RESULTS: Readmission rates at 90 days were 24% for RARC and 23% for ORC (p=0.842). At 1 year the respective rates were 29.3% for RARC and 28.3% for ORC (p=0.841). sFI ³3 was a significant predictor of readmission at both time points (OR 6.05, 1.79-20.48, p=0.004 at 90days and OR 9.55, 1.69-53.77, p=0.011 at 1 year). Surgical approach (RARC or ORC), diversion type, lymphadenectomy, age, sex, T or N stage, and BMI were not predictive of readmission (Table 1). CONCLUSIONS: Postoperative readmission rates do not differ between RARC and ORC in this prospective analysis from the RAZOR trial. sFI was the only identifiable factor predicting readmission and surgical approach, diversion, chemotherapy, lymphadenectomy, etc. were not significant predictors. This data suggests that patient factors like frailty contribute significantly to recovery from a major procedure like RC. This study provides important prospective data for patient counseling and reiterates the importance of prospective trials to evaluate different surgical techniques before drawing conclusions regarding readmission rates.Source of Funding: The RAZOR trial was supported by the National Institutes of Health (NIH) National Cancer Institute (NCI; grant number 5RO1CA155388).

Multicenter Analysis of Postoperative Complications in Octogenarians After Radical Cystectomy and Ureterocutaneostomy: The Role of the Frailty Index.

The purpose of this study was to assess patient frailty as a risk factor for radical cystectomy (RC) complications. We performed an analysis of prospectively collected data of consecutive patients 80 years of age or older who underwent RC and ureterocutaneostomy in 6 primary care European urology centers. Frailty was measured using a simplified frailty index (sFI) with a 5-item score including: (1) diabetes mellitus; (2) functional status; (3) chronic obstructive pulmonary disease; (4) congestive cardiac failure; and (5) hypertension, with a maximum 5-item score meaning high level of frailty. Within 90 days surgical complications were scored according to the Clavien Classification System (CCS). sFI≥3 was considered as poor frailty status. Clinical and pathological variables were analyzed as predictors of severe complications (CCS≥3). One hundred seventeen patients were enrolled. Most patients reported an sFI score of 2 and 3, respectively, 31/117 (26.5%) and 45/117 patients (38.5%). CCS≥3 occurred in 17/117 patients (14.5%). Patients with sFI≥3 were significantly older than patients with sFI<3 (median age, 85 years [interquartile range (IQR), 82-86] versus 82 years [IQR, 80-84]; P= .001). Most CCS≥3 scores occurred in patients with sFI≥3: 13 (11.1%) versus 4 (3.4%; P= .02). No significative differences were detected in terms of length of hospital stay, pathological stage, and postoperative bowel canalization when related to sFI. sFI≥3 was an independent risk factor of CCS≥3 in univariate and multivariate analysis (respectively, odds ratio [OR], 3.81 [95% confidence interval (CI), 1.16-12.5; P= .02] and OR, 3.1 [95% CI, 0.7-13.7; P= .01]). Body mass index, age, American Society of Anesthesiologists score≥3, and pathological stage were not related to CCS≥3. RC appears feasible in elderly patients with an sFI<3. In cases of sFI≥3, this choice should be carefully valued, discussed, and possibly avoided because of a higher risk of complications.