Outcomes In Routine Clinical Practice Research Articles

Using Progress Feedback to Enhance Treatment Outcomes: A Narrative Review.

We face increasing demand for greater access to effective routine mental health services, including telehealth. However, treatment outcomes in routine clinical practice are only about half the size of those reported in controlled trials. Progress feedback, defined as the ongoing monitoring of patients' treatment response with standardized measures, is an evidence-based practice that continues to be under-utilized in routine care. The aim of the current review is to provide a summary of the current evidence base for the use of progress feedback, its mechanisms of action and considerations for successful implementation. We reviewed ten available meta-analyses, which report small to medium overall effect sizes. The results suggest that adding feedback to a wide range of psychological and psychiatric interventions (ranging from primary care to hospitalization and crisis care) tends to enhance the effectiveness of these interventions. The strongest evidence is for patients with common mental health problems compared to those with very severe disorders. Effect sizes for not-on-track cases, a subgroup of cases that are not progressing well, are found to be somewhat stronger, especially when clinical support tools are added to the feedback. Systematic reviews and recent studies suggest potential mechanisms of action for progress feedback include focusing the clinician's attention, altering clinician expectations, providing new information, and enhancing patient-centered communication. Promising approaches to strengthen progress feedback interventions include advanced systems with signaling technology, clinical problem-solving tools, and a broader spectrum of outcome and progress measures. An overview of methodological and implementation challenges is provided, as well as suggestions for addressing these issues in future studies. We conclude that while feedback has modest effects, it is a small and affordable intervention that can potentially improve outcomes in psychological interventions. Further research into mechanisms of action and effective implementation strategies is needed.

Hand Grip and Pinch Strength in a Healthy Children Norms for 6 to 18 Years in Al-Kharj City, Kingdom of Saudi Arabia

Background: Measuring and comparing grip and pinch strengths with their normative data is a valid method to detect intensity of the numerous damages of hand. The aim of the study was to establish the normative data of grip strength and three types of pinch strengths (Key, Tip and Palmar) in healthy Saudi’s children. Method: In this cross-sectional study, of grip strength and three types of pinch strengths (Tip, Key and Palmar) were recorded for 82 healthy children (41 boys and 41 girls) heathy children aged 7-18 years. The Camry Electronic Hand Dynamometer and Hydraulic Pinch Gauge were used to measure grip strength and pinch strength, respectively. Result: Normative data of grip and pinch strengths were provided. Grip and pinch strengths of both genders were close to each other’s and increasing consistently with increasing age. The maximum grip strength and pinch strength was obtained in the group of 14-18 years among both genders. In addition: Study results showed that there was a significant association between weight and all the hand grip strength and pinch strength (p < 0.05) in boys whereas BMI considered as an effective parameter on grip strength and tip pinch strength in girls. Conclusions: Findings from the present study provide reference values for hand grip strength and pinch strength for healthy children from 6- which will be useful to guide rehabilitation outcomes in routine clinical practice.18 years of age which will be useful to guide rehabilitation outcomes in routine clinical practice.

Abstract 3821: Real world outcomes among patients with newly diagnosed acute myeloid leukemia

Abstract Introduction: Treatment options for patients with acute myeloid leukemia (AML) have expanded in recent years. Although new treatments have demonstrated efficacy in clinical trials, less is known about their effect on outcomes in routine clinical practice. We examined outcomes for patients with newly-diagnosed AML (ND-AML) using real world data (RWD). Methods: This retrospective observational study was conducted using the COTA real-world (rw) database, a de-identified source of longitudinal electronic health record data pertaining to the diagnosis, management, and outcomes of patients with cancer. Adult patients with ND-AML, diagnosed January 1, 2013 to March 20, 2023 were included. First-line treatment regimens were grouped into therapeutic categories and outcomes were summarized. The index date was defined as date of initiation of first-line therapy. Results: Among 2516 patients with ND-AML included (Table), the most common regimens used were intensive chemotherapy with cytarabine (IC w/ara-C), hypomethylating agents with venetoclax (HMA+ven), and HMA alone. Complete response rate was highest in patients treated with IC w/ara-C or investigational regimen(s). Median overall survival (OS) was 16 mo overall, with highest median OS seen in patients treated with IC w/ara-C and investigational regimen(s). Median OS for patients treated with HMA+ven was 13.5 mo. Thirty-day mortality was lowest in patients treated with IC w/ara-C, CPX-351 (liposomal daunorubicin + cytarabine), and HMA+ven. Conclusions: Results suggest that IC w/ara-C remains the standard of care for most patients with ND-AML and this regimen has a higher CR rate and median OS. Variation of patient demographics and clinical characteristics across treatment groups did not permit cross-treatment comparisons, though future analyses evaluating these subgroups may provide further insight into effectiveness and safety of AML regimens in routine care for populations underrepresented in clinical trials. rwCR rate Median rwOS 30-day mortality N % (95% CI) Months (95% CI) % (95% CI) Overall 2516 45.3 (43.2, 47.3) 16.0 (14.9, 17.3) 5.9 (5.0, 6.8) IC w/ara-C 1171 60.6 (57.8, 63.4) 36.4 (31.0, 46.0) 1.6 (0.9, 2.3) HMA+ ven 300 33.7 (28.3, 39.3) 13.5 (11.4, 15.5) 3 (1.1, 4.9) Decitabine 242 12.8 (8.9, 17.7) 8.4 (6.7, 9.9) 10.4 (6.5, 14.2) Azacitidine 206 7.8 (4.5, 12.3) 7.2 (5.3, 9.6) 10.7 (6.4, 14.8) Investigational 206 61.6 (54.6, 68.3) 21.3 (15.2, 27.8) 3.4 (0.9, 5.9) Lower dose cytarabine 62 12.9 (5.7, 23.9) 8.7 (5.4, 16.1) 14.9 (5.4, 23.4) CPX-351 based 61 55.7 (42.4, 68.5) 9.3 (7.3, 15.1) 0.0 No treatment 188 NA 1.9 (1.5, 2.8) 30 (22.7, 36.6) Citation Format: Elizabeth D. Pulte, Laura L. Fernandes, Joseph Wynne, Eric Hansen, Andrew J. Belli, Anna Barcellos, Christina M. Zettler, Rebecca Bystrom, Jonathon Vallejo, Wenjuan Gu, Catherine Lerro, Kelly Norsworthy, Angelo DeClaro, Marc R. Theoret, Donna Rivera, Ching-Kun Wang. Real world outcomes among patients with newly diagnosed acute myeloid leukemia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3821.

Real-world outcomes of Italian patients with advanced non-squamous lung cancer treated with first-line pembrolizumab plus platinum-pemetrexed

PurposeThe aim of this multi-center, retrospective/prospective cohort observational study was to evaluate outcomes in routine clinical practice of first-line chemo-immunotherapy with cis/carboplatin, pemetrexed and pembrolizumab in patients with advanced non-squamous non-small cell lung cancer (NSCLC) in 33 Italian centers. MethodsThe outcome measure was to evaluate overall survival (OS) in a real-world patient population. Secondary endpoints were: progression-free survival (PFS), objective response rate (ORR), duration of response (DoR) and incidence of treatment-related adverse events (AEs). Results1068 patients were enrolled at the time of data cut-off (January 31st, 2023), and 812 (76.0%) belonged to the retrospective cohort. Median age was 66 years (27−85), ECOG PS was ≥ 2 in 91 (8.6%) patients; 254 (23.8%) patients had brain metastases at baseline; 38 (3.6%) patients had tumor with PD-L1 expression ≥ 50%. After a median follow-up of 17.0 months (95% CI, 16.1–17.9), median OS was 16.1 months (95% CI, 14.4–18.8) and PFS was 9.9 months (95% CI, 8.8–11.2). Median DoR (n = 493) was 14.7 months (95% CI, 13.6–17.1). ORR was 43.4% (95% CI, 40.4–46.4). Any-grade AEs occurred in 636 (59.6%) patients and grade ≥ 3 in 253 (23.7%) patients. Most common grade ≥ 3 AEs were neutropenia (6.3%) and anemia (6.3%). ConclusionsFirst-line chemo-immunotherapy was effective and tolerable in this large, real-world Italian study of patients with advanced non-squamous NSCLC. Our results were in line with the KEYNOTE-189 registration study, also considering the low number of PD-L1 ≥ 50% patients included in our study.

Atezolizumab plus bevacizumab (A+B) in patients with unresectable hepatocellular carcinoma (uHCC): Real-world experience from a US community oncology network.

447 Background: A+B is the standard first-line (1L) treatment for uHCC based on the IMbrave150 trial, which demonstrated superior efficacy over sorafenib with longer median overall survival (19.2 vs 13.4 months) and progression-free survival (6.8 vs 4.3 months) among patients with Child Pugh (CP) A cirrhosis. Evidence about A+B use and outcomes in routine clinical practice, including in patients with impaired liver function, remains limited. Methods: This retrospective observational study included adult patients who initiated 1L A+B for uHCC within The US Oncology Network between 1/1/2019 and 8/31/2022 (followed through 11/30/2022) using structured and unstructured electronic health records (EHR) based data. CP classes were reported by physicians or derived from risk factors. Kaplan-Meier methods were used to assess real-world overall survival (rwOS) and progression-free survival (rwPFS) from initiation of A+B. Exploratory subgroup analyses were conducted by CP class, albumin-bilirubin (ALBI) grade, liver disease etiology, and race/ethnicity. Results: We identified 374 patients with uHCC who initiated 1L A+B during the study period. Compared with patients enrolled in IMbrave150 (n=336), those treated with A+B in clinical practice were older (median age: 69 vs 64 years), had worse liver function (CP A: 61% vs 100%; ALBI Grade >1: 66% vs 43%), and had poorer performance status (ECOG PS>1: 18% vs 0%). At a median follow-up of 5.6 months, 78% (n=293) had discontinued treatment. Among them, 57% discontinued was progression and 4% discontinued due to toxicity alone. Median rwOS was 13.2 months (95%CI: 9.5–15.9) and median rwPFS was 6.4 months (95%CI: 5.1–7.7). Subgroup results are shown (Table). Conclusions: In community oncology settings, 1L A+B demonstrates effectiveness in diverse patient cohorts, including those with impaired liver function, non-viral liver disease, and racial/ethnic minorities. Predictive biomarkers can help identify subgroups who may most benefit from 1L A+B. [Table: see text]

Vatari Guggulu, Hingvashtaka Churna, and Brihat Saindhavadya Taila in the management of rheumatoid arthritis: An open-label, prospective, single-arm multi-center study

Abstract Background: Despite significant advances in the diagnosis and treatment of rheumatoid arthritis (RA), the clinical outcomes remain unsatisfactory in a significant proportion of patients. Ayurveda management for RA (Amavata) has shown promising clinical outcomes in routine clinical practice and as per published research studies. Objective: The study was designed to assess the therapeutic effect and safety of Ayurveda interventions, Vatari Guggulu (VG), Hingvashtaka Churna (HC), and Brihat Saindhavadya Taila (BS) in the management of RA. Materials and Methods: An open-label, prospective, single-arm multicenter study was conducted at Ayurveda Research Institutes in Patna, Bhubaneswar, and Guwahati with a sample size of 180 participants. Patients of any gender aged 20–60 years with clinically diagnosed RA as per the revised American College of Rheumatology criteria and willing to provide written informed consent to participate in the study were included in the study. Ayurveda interventions, VG, HC, and BS, were administered to the study participants for 12 weeks, with a follow-up at four weeks without intervention. The primary outcome measure was a change in the Disease Activity Score-28 (DAS28) from baseline. The other outcome measures included change in the Indian Health Assessment Questionnaire Disability Index score (HAQ-DI), changes in the acute phase reactants (erythrocyte sedimentation rate [ESR] and C-reactive protein [CRP]), and change in the quality of life parameters (assessed through the SF-36 questionnaire). Results: A total of 180 participants were enrolled in the study, and data of 179 participants were considered for the final analysis. A statistically significant difference was observed in the outcome parameters, such as a mean change in the DAS28 score, HAQ-DI score, SF-36 score, and ESR and CRP levels (P < 0.001) after 12 weeks of treatment. The mean DAS28 score changed from 6.50 ± 0.790 at baseline to 4.21 ± 1.286 on week 16 follow-up (P < 0.001). No participant withdrew from the study due to adverse events. The trial interventions were well-tolerated and safe. Conclusion: The study outcomes provide preliminary evidence of the safety and potential benefits of the Ayurveda interventions in the management of RA. Further, randomized controlled studies may be planned to generate robust evidence on the therapeutic potential of these interventions so that they can be recommended for use in routine clinical practice. Trial registration: CTRI/2014/12/005242.

Implementation of the Treat-to-Target Approach in Psoriatic Arthritis and Its Outcomes in Routine Clinical Practice.

Background Measuring disease activity in psoriatic arthritis using validated tools and treating to a target (T2T) is advocated. It improves quality of life and delays radiographic progression. In clinical practice, it guides therapy escalation to achieve better disease control. This study aimed to assess the real-life implementation of the T2T concept in daily clinical practice and the proportion of patients achieving the target of low disease activity or remission. Methodology In this study, a retrospective review of patients diagnosed with psoriatic arthritis having clinical visits from January 2020 to February 2023 was done. The proportion of patients in whom disease activity was monitored using the Disease Activity Index for Psoriatic Arthritis (DAPSA) 28 and Physician Global Assessment (PGA) and those achieving the target was calculated using SPSS version 21 (IBM Corp., Armonk, NY, USA). Results A total of 89 patients were included in the study after fulfilling the inclusion and exclusion criteria. Overall, 56.2% (50) of patients were males and 43.8% (39) were females, with a mean age of 43.5 ± 14.5 years, mean disease duration of 6.6 ± 3.8 years, and mean follow-up duration of 2.8 ± 1.6 years. Of the study population, 43.8% (39) had axial involvement, 23.6% (21) had dactylitis, and 12.4% (11) had enthesitis. Skin psoriasis was present in 84.3% (75), 11.2% (10) had a family history of psoriasis, 19.1% (17) had nail changes, 1.1% (1) had uveitis, and in 94.8% (73) of patients skin psoriasis presented before arthritis. Overall, 97.7% (85) of patients were on conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), with the most common being methotrexate in 77%, followed by leflunomide in 8%. Further, 34.8% (31) were using biological DMARDs (bDMARDs), with the most common being tofacitinib (33.7%), infliximab (28.1%), and secukinumab (24.7%) being other choices. Overall, 21.1% (18) of patients experienced adverse events with csDMARDs and 3.2% (1) with biological DMARDs. DAPSA28 was recorded in 44.9% (40), Psoriasis Area and Severity Index in 16.8% (15), and PGA in 100% of patients. Target of low disease activity (LDA)/remission was achieved in 50.6% (45) patients, as assessed by PGA or DAPSA28 cutoff. The LDA/remission target was achieved in 51.2% of patients taking csDMARDs, and 74.2% in those who were on bDMARDs. Conclusions It is crucial to measure the disease activity using validated tools and treat the patient to target for achieving better disease control and improved quality of life. Despite the evidence that T2T improves outcomes, it is not widely practiced in routine clinical practice.

Electronic-PRO Measures for adverse events Of Treatment In ONcology (E-PROMOTION)

PurposeCancer patients struggle with the trauma of the disease and its treatment. PRO-CTCAE was developed to improve the recording of underreported symptomatic toxicities. We evaluated the improvement and ease in reporting symptomatic adverse events through add-on PRO-CTCAE (via a mobile application) compared to standard clinician-reported outcomes in routine clinical practice. We also evaluated changes in the health-related quality of life (HRQoL). Methods110 cancer patients were studied for three weeks between their first and second chemotherapy session. HRQoL was assessed using EORTC QLQ-c30. ResultsFifty-three patients self-reported their symptomatic adverse events on the day 7th & day 14th after the first cycle of chemotherapy. For the other fifty-seven patients, recording of adverse events was done by standard clinician-reported outcomes. All the patients in the study group reported adverse events compared to only 21 % in the standard reporting group. All 15 domains of adverse events were reported in the self-reporting group compared to only 5 in the standard reporting group. The self-reporting group had a significantly better overall quality of life. ConclusionsSelf-reporting of adverse events using mobile app-based PRO-CTCAE helps patients and clinicians with better documentation of symptomatic toxicities of chemotherapy, reducing the burden on physicians and improving patient satisfaction. Mobile app-based self-reporting empowers cancer patients undergoing treatment, improves their quality of life, and should be implemented in routine clinical practice. Wider implementation can lead to further optimised solutions.

Outcomes in Routine Clinical Practice with Methotrexate-Temozolomide-Rituximab Induction and Modified Etoposide-Cytarabine Consolidation in Newly Diagnosed Primary CNS Lymphoma

Background: Recent studies have reported improved outcomes for patients with Primary CNS lymphoma (PCNSL) with addition of agents in induction (for e.g. cytarabine, thiotepa and rituximab in IELSG studies), intense consolidation (Autologous stem cell transplant (ASCT) as in IELSG 43) and intense non-myeloablative chemotherapy with etoposide/cytarabine (EA) as in CALGB 50202). Delivery of such an intense therapy is often difficult in clinical practice due to advanced age, comorbidities, poor performance status and resource constraints. We started using induction with methotrexate, temozolomide and rituximab (MTR) as per CALGB 50202 study however the intense non-myeloablative EA consolidation was not feasible. We used a strategy of reduced dose EA consolidation for 2 cycles with etoposide at 100 mg/m 2 over 2 hours and cytarabine 2 gm/m 2 twice daily for 2 or 3 days based on clinical judgement of the treating physician. Here we report outcomes with this approach in newly diagnosed PCNSL patients treated at our centre. Method: We did a retrospective analysis of patients with newly diagnosed PCNSL treated with MTR induction followed by modified EA consolidation. Kaplan-Meier was used to estimate progression free (PFS) and overall survival (OS). Variables influencing the outcomes with P less than 0.05 were considered significant. Results: Between January 2015 to December 2022, 72 patients were treated with above protocol with a median age of 46.5 years (range, 17 to 68 years) and 50 (69.4%) were males. Median ECOG performance score at presentation was 1 with 16 (22%) patients having ECOG performance score of 3 or more. IELSG scores were high and intermediate risk in 26 (36.1%) and 27 (37.5%) respectively while only 7 (9.7%) were in the low risk (data was not available for remaining 12 (17%) patients). MSKCC scores were available for all patients with 43 (59%) patients in class 1, 14 (19%) patients in class 2 and 15 (20%) patients in class 3. MTR induction with a dose of 8 gm/m2 could be delivered for all 4 cycles in 64 (88%) patients. Dose reduction was required in 14 (19.4%) patients; reasons were renal dysfunction in 8 (11%), infections in 3 (4%), liver dysfunction in 2 (3%). Nine patients (12.5%) had disease progression during induction. Total of 54 patients received consolidation with systemic therapy. Dose reduced EA consolidation was delivered in 46 (63%) patients while 8 patients received single agent high dose cytarabine consolidation and only 3 patients underwent ASCT. Seven patients received WBRT consolidation. EA consolidation was given for 2 days in 30 (65%) patients while 16 (35%) patients received 3 days of EA consolidation. Twenty six patients received maintenance lenalidomide. With a median follow up of 39.2 months (range, 2.1 to 91), median PFS is 46.9 months and median overall OS has not reached. Three years PFS & OS for all patients is 59.5% and 78% respectively ( Fig 1A &B). Median PFS and OS of patients receiving EA consolidation has not been reached with a 3-year PFS and OS of 77% and 79% respectively. MSKCC score was predictive of OS with 3 year OS in class 1, 2 and 3 of 89.5%, 68% and 58% respectively. Consolidation with split dose EA was associated with better OS and PFS as compared to single agent cytarabine alone. None of the 3 patients receiving ASCT have relapsed. Patients receiving full dose methotrexate had better OS compared to patients requiring dose reduction. Two versus 3 day EA consolidation had no impact on OS. MTR induction was well tolerated with grade 3 or more toxicity as follows: renal dysfunction in 8 (11%) patients, transaminitis in 4 and febrile neutropenia in 4 patients with no treatment related deaths. EA consolidation resulted in 18 episodes of febrile neutropenia with two deaths. Grade 3 or more hematologic toxicities were common with grade 3 or more anaemia, neutropenia and thrombocytopenia in 15 (32%), 40 (86%), 33 (71%) patients respectively. There were two deaths in the consolidation phase, one due to intracranial bleeding and another due to febrile neutropenia. Conclusion: MTR induction with modified EA consolidation is feasible and results in optimal outcomes in real world setting. Higher cumulative methotrexate dose and use of EA consolidation were associated with better OS. These outcomes compare favourably to CALGB 50202 study and represent a feasible option in resource limited setting.

Real-World Analysis of Treatment Patterns and the Effectiveness and Safety Profile of Daratumumab-Based Regimens in Chinese Patients with Newly Diagnosed or Relapsed/Refractory Multiple Myeloma

Introduction: Daratumumab (DARA) is a human IgGκ monoclonal antibody targeting CD38 with a direct on-tumor and immunomodulatory mechanism of action. Several clinical trials have established DARA-based treatment as a standard of care globally for patients with newly diagnosed or relapsed/refractory multiple myeloma (MM). However, clinical trials do not always reflect routine clinical practice, and real-world (RW) studies thus provide an important complement to conventional clinical trials. Herein, we report results from an observational study that described RW treatment patterns and outcomes in routine clinical practice among patients with MM who were treated with DARA in China. This is possibly the first study to enroll a large population of Chinese patients with MM who were treated with DARA in the RW setting. Methods: This ongoing, multicenter, noninterventional, observational registry study is enrolling Chinese patients who have been diagnosed with symptomatic newly diagnosed or relapsed/refractory MM and either (1) started DARA treatment after August 1, 2019, and were expected to continue ongoing DARA at the time of study initiation (November 3, 2021) or (2) started DARA treatment after study initiation. Patients were excluded from the study if they had received ≥4 prior lines of MM therapy before starting DARA-based treatment or had a diagnosis of other cancers prior to their MM diagnosis. The decision to treat with DARA must have been made prior to and independently of the patient's inclusion in the study, and treatment was administered in accordance with local clinical practice. For patients who started DARA after August 1, 2019, but before study initiation, data were collected both retrospectively through medical chart review and prospectively after enrollment. RW baseline disease characteristics, treatment patterns, response rates, measurable residual disease (MRD), and safety are presented. Outcome and safety analyses were based on the DARA treatment period. Results: As of the cutoff date (April 30, 2023) for this analysis, 210 patients who received ≥1 dose of DARA have been enrolled in the study from 13 participating sites in China. At baseline (last status prior to the first DARA dose), patients had a median age of 64 y (range, 29-89) and a median time since MM diagnosis of 1 y (range, 0-12); the majority of patients had an ECOG performance status of 0 or 1 (82.4%) and a Durie-Salmon MM stage of III (74.4%). Most (83.8%) patients had received ≥1 prior line of therapy before initiating DARA, including 82.4% who had received prior protease inhibitors (PIs) and 58.1% who had received prior immunomodulatory drugs (IMiDs). A summary of prior therapies is provided in Table 1. DARA-based therapy included DARA monotherapy (n = 22) or combination with dexamethasone only (n = 21), PIs ± dexamethasone (n = 57), IMiDs ± dexamethasone (n = 71), PIs and IMiDs ± dexamethasone (n = 29), and other combinations (n = 10). The median DARA exposure time was 5.39 mo (interquartile range [IQR], 2.56-9.69), and the median follow-up time was 10.48 mo (IQR, 7.23-15.31). Of the 179 patients evaluable for response, a best overall response of partial response (PR) or better was achieved by 130 (72.6%) patients and a best response of very good partial response (VGPR) or better was achieved by 93 (52.0%) patients, with responses observed across DARA treatment regimens ( Table 2). MRD results were available for 53/179 (29.6%) patients, with 31/53 (58.5%) patients achieving MRD negativity. Adverse drug reactions were reported for 40 (19.0%) patients overall; events reported in ≥5% of patients included leukopenia (6.2%), thrombocytopenia (5.7%), and neutropenia (5.2%). Serious treatment-emergent adverse events were reported for 29 (13.8%) patients, with pneumonia (n = 10, 4.8%) the only serious event reported in ≥5 patients. Twenty-five patients died as of the cut-off date, regardless of timing (with/without DARA treatment period). Conclusions: This noninterventional, observational study provides RW insights into physician treatment decisions for patients with MM in China and the characteristics of patients who are selected for DARA-based treatment. In addition, the RW effectiveness, duration of therapy, and safety results support the use of DARA-based treatment as a standard of care in Chinese patients with newly diagnosed or relapsed/refractory MM. This study is ongoing, with a total planned enrollment of ~220 patients.

Prognostic value of the right ventricular ejection fraction using three-dimensional echocardiography: Systematic review and meta-analysis.

Three-dimensional echocardiography (3DE) is a robust method for measuring the right ventricular (RV) ejection fraction (EF), which is closely associated with outcomes. We performed a systematic review and meta-analysis (1) to examine the prognostic value of RVEF and (2) to compare its prognostic value with that of left ventricular (LV) EF and LV global longitudinal strain (GLS). We also performed individual patient data analysis to validate the results. We searched articles reporting the prognostic value of RVEF. Hazard ratios (HR) were re-scaled using the within-study standard deviation (SD). To compare predictive values of RVEF and LVEF or LVGLS, the ratio of HR related to a 1-SD reduction of RVEF versus LVEF or LVGLS was calculated. Pooled HR of RVEF and pooled ratio of HR were analyzed in a random-effects model. Fifteen articles with 3,228 subjects were included. Pooled HR of a 1-SD reduction of RVEF was 2.54 (95% confidence interval (CI): 2.15-3.00). In subgroup analysis, RVEF was significantly associated with outcome in pulmonary arterial hypertension (PAH) (HR: 2.79, 95% CI: 2.04-3.82) and cardiovascular (CV) diseases (HR: 2.23, 95%CI: 1.76-2.83). In studies reporting HRs for both RVEF and LVEF or RVEF and LVGLS in the same cohort, RVEF had 1.8-fold greater prognostic power per 1-SD reduction than LVEF (ratio of HR: 1.81, 95%CI: 1.20-2.71), but had predictive value similar to that of LVGLS (ratio of HR: 1.10, 95%CI: 0.91-1.31) and to LVEF in patients with reduced LVEF (ratio of HR: 1.34, 95%CI: 0.94-1.91). In individual patient data analysis (n = 1,142), RVEF < 45% was significantly associated with worse CV outcome (HR: 4.95, 95% CI: 3.66-6.70), even in patients with reduced or preserved LVEF. The findings of this meta-analysis highlight and support the use of RVEF assessed by 3DE to predict CV outcomes in routine clinical practice in patients with CV diseases and in those with PAH.

Discordances Between Creatinine- and Cystatin C–Based Estimated GFR and Adverse Clinical Outcomes in Routine Clinical Practice

Cystatin C is recommended for measuring estimated glomerular filtration rate (eGFR) when estimates based on creatinine (eGFRcr) are not thought to be accurate enough for clinical decision making. While global adoption is slow, routine cystatin C testing in Sweden has been available for over a decade, providing real-world evidence about the magnitude of differences between eGFRcys and eGFRcr and their association with clinical outcomes. Observational study. 158,601 adults (48% women; mean age 62 years, eGFRcr 80, and eGFRcys 73mL/min/1.73/m2) undergoing testing for creatinine and cystatin C on the same day in connection with a health care encounter during 2010-2018 in Stockholm, Sweden. Percentage difference of eGFRcys minus eGFRcr (eGFRdiff). Kidney failure with replacement therapy (KFRT), acute kidney injury (AKI), atherosclerotic cardiovascular disease (ASCVD), heart failure, and death. Multivariable Cox proportional hazards regression. Discordances between eGFRcr and eGFRcys were common, with eGFRcys being lower than eGFRcr (negative eGFRdiff) in most cases (65%). Patients with larger negative eGFRdiff were older, more often female, with higher eGFRcr and albuminuria, and more comorbid conditions. Compared with patients with similar eGFRcys and eGFRcr, the lowest quartile (eGFRcys > 27% lower than eGFRcr) had the higher HR of all study outcomes: AKI, 2.6 (95% CI, 2.4-2.9); KFRT, 1.4 (95% CI, 1.2-1.6); ASCVD, 1.4 (95% CI, 1.3-1.5); heart failure, 2.0 (95% CI, 1.9-2.2); and all-cause death, 2.6 (95% CI, 2.5-2.7). Conversely, patients in the highest quartile (positive eGFRdiff) were at lower risk. Observational study, lack of information on indications for cystatin C testing. Cystatin C testing in routine care shows that many patients have a lower eGFRcys than eGFRcr, and these patients have a higher risk of multiple adverse outcomes. Clinicians require guidance when there are discrepancies between the estimated glomerular filtration rate based on creatinine (eGFRcr) and based on cystatin C (eGFRcys) in the same individual. Routine cystatin C testing in Sweden for over a decade permits exploration of how common and large these discrepancies are, and their associations with adverse clinical outcomes. In this observational study, we found that discordances between eGFRcys and eGFRcr are common, and 1 in 4 patients tested had an eGFRcys > 28% lower than their eGFRcr. We also show that an eGFRcys that is lower than the eGFRcr consistently identifies patients at higher risk of adverse outcomes, including cardiovascular events, kidney replacement therapy, acute kidney injury, and death.

Real world evidence of systemic therapy in hormone receptor positive advanced breast cancer (HR+ ABC) in Australia: ARORA Registry.

e13054 Background: The last decade has seen a rapid increase in systemic treatment options for patients with HR+ ABC. The incorporation of CDK4/6 inhibitors in first line (1L) is now standard practice leading to improved survival. However, there is a paucity of data on uptake of standard therapies and associated toxicities in the real-world setting. Methods: ARORA is a secondary data use study of Australian patients with HR+ ABC capturing prospective data on patient characteristics, systemic therapy sequencing and treatment outcomes in routine clinical practice. Patients aged &gt; 18 diagnosed after 1 Jan 2020 are eligible. Results: Data from 294 patients at 16 sites was analysed with a median follow up of 15 months. Mean age was 63 years; 23% &gt; 75 years. 64% were ECOG 0, 5.4% had a familial syndrome, 61% had relapsed metastatic disease and 19.4% had bone only metastases at diagnosis. Of patients who relapsed, 14.6% and 52.8% received neoadjuvant and adjuvant chemotherapy respectively, and 77.5% received adjuvant endocrine therapy (ET). 41% relapsed on or within 12 months of stopping adjuvant ET. 5 patients (1.7%) did not receive any systemic therapy for ABC. Of those on 1L therapy, 223 (77%) received CDK4/6i + ET, 38 (13.1%) received ET alone and 26 (9%) received chemotherapy. Choice of 1L CDK4/6i was palbociclib (50.7%), ribociclib (34.5%) and abemaciclib (9.9%). Patients who received 1L ET alone were older (mean age 75 vs 62 years; 68.4 vs 16.6% &gt; 75 years) with poorer performance status (34.2 vs 6.3% ECOG ≥2) and more comorbidities (76.3 vs 36.8% Charlson index &gt; 2) compared to those who received 1L CDK4/6i + ET. Conversely, those on 1L chemotherapy were younger (mean age 54, 96.2% &lt; 75years), with better performance status (69.2% ECOG 0-1) and fewer comorbidities (88.5% Charlson index &lt; 2). Patients receiving 1L chemotherapy were more likely to have visceral metastases compared to those on CDK4/6i + ET (69.2 vs 43.1%, p = 0.01). The most common reported toxicities in patients receiving CDK4/6i were diarrhea (59% abemaciclib vs 3.9% ribociclib vs 2.7% palbociclib), neutropenia (38.1% palbociclib vs 32.5% ribociclib vs 22.7% abemaciclib) and nausea/vomiting (27.3% abemaciclib vs 22.1% ribociclib vs 12.4% palbociclib). Abnormal LFTs occurred in 9.1% of patients on abemaciclib (vs 3.9% ribociclib and &lt; 1% palbociclib). 2 patients (1.8%) on palbociclib had pneumonitis whilst 1 (1.3%) on ribociclib had QTc prolongation. Survival data is immature. Conclusions: Despite CDK4/6i + ET being gold standard treatment in 1L HR+ ABC, only 3/4 of patients received this combination, with a substantial minority receiving ET alone or chemotherapy. Age, ECOG status, comorbidity burden and presence of visceral disease appear to be major determinants of treatment choice. Toxicity profile of the CDK4/6i agents were mostly in line with clinical trial results, although longer follow up is needed to confirm this.

The evolution of treatment patterns in patients (pts) with locally advanced or metastatic urothelial cancer (la/mUC) and clinical outcomes: Results of a longitudinal observational cohort study in England.

e16559 Background: Treatment (tx) guidelines for pts with la/mUC in England have evolved over the last decade following the approval of successive immune checkpoint inhibitors (ICIs). However, the impact of this evolution on routine clinical practice (RCP) remains unclear. We aimed to describe shifts in tx patterns and associated clinical outcomes in RCP in England. Methods: This retrospective cohort study included pts aged ≥18 years, with primary stage III/IV UC diagnosis (dx) between Jan 1, 2013 and Dec 31, 2020, in the National Cancer Registration Dataset with follow-up to May 31, 2022. Pts’ dx were stratified at Dec 31, 2017, to split the cohort into pre- and post-ICI eras. Lines of systemic therapy were derived via an algorithm using data from the Systemic Anti-Cancer Therapy dataset. Summary statistics and overall survival (OS) were calculated and compared using χ2 and log-rank tests, respectively. The Kaplan-Meier method was used to estimate median OS from dx and from systemic tx initiation. Results: In the pre- and post-ICI groups, the majority of pts were male (65.7% and 65.5%) and mean modified Charlson-Deyo Comorbidity Index was 3.4 and 3.5, respectively. Mean age was 73.2 years in both groups, while a higher percentage of pts in pre-ICI era had stage IV disease at dx (68.3% and 50.0%; p&lt;0.001). The rate of first line (1L) tx increased from 30.4% to 35.3% (p&lt;0.001) and second line (2L) from 31.2% to 37.3% (p&lt;0.001). The proportion of pts who received ICI in any line increased from 13.7% to 31.6% (p&lt;0.001). Median OS from 1L tx improved from 13.8 to 15.5 mo. Conclusions: While pt demographics did not change considerably between the two groups, 1L and 2L tx rates moderately increased over time, although remained below 40%. In both groups, &gt;85% of treated pts received 1L platinum chemotherapy, consistent with guidelines. In the post-ICI era, approximately one-third of treated pts received ICI therapy in any line. Improved OS from 1L tx could be partially attributable to the increased availability and uptake of ICIs. [Table: see text]

Real-world outcomes associated with use of front-line bevacizumab in ovarian cancer

BackgroundIn the pivotal ICON7 study, addition of bevacizumab to front-line treatment of ovarian cancer (OC) significantly improved overall survival (OS) (p = 0.03) in a high-risk subgroup of patients with suboptimally debulked/unresectable stage III or IV disease, leading to approval in Ontario, Canada in March 2016. Here we describe utilization of bevacizumab for front-line, high-risk OC and determine outcomes in routine clinical practice. MethodsProvincial administrative databases were utilized to identify all patients treated with front-line bevacizumab following its approval. Median OS (mOS) was determined using the Kaplan-Meier method. Factors associated with OS were identified using a Cox proportional hazard model. A comparative effectiveness analysis was performed to determine mOS pre- (2006–2016) and post- (2016–2019) approval. ResultsFrom March 2016 to October 2019, 282 patients received bevacizumab. Mean age was 64 years old, and 58% had stage IV disease. Median survival was 29 months and was longer in stage III (37 months) compared to stage IV disease (28 months). In a comparative effectiveness analysis of patients with stage IV serous OC, post-approval uptake of bevacizumab was low (23%). Median OS was similar pre (26 months) and post (27 months) approval (HR 0.92, 0.75–1.12, p = 0.383). ConclusionsSurvival in real-world patients treated with front-line bevacizumab is shorter than in pivotal clinical trials. Survival in stage IV serous patients has not significantly improved post public reimbursement of bevacizumab. This analysis was limited by poor uptake, however mOS was similar in patients who did and did not receive bevacizumab.

Abstract TMP91: Patterns And Outcomes Of Endovascular Thrombectomy Among Patients Over Age 80: The Florida Stroke Registry

Introduction: Patients older than 80 years of age are under-represented in randomized trials of endovascular thrombectomy (EVT). In the large Florida Stroke Registry, we aimed to evaluate the impact of age on EVT outcomes in routine clinical practice. Methods: Prospectively collected data from Get with the Guidelines- Stroke hospitals participating in the Florida Stroke Registry from January 2010 to April 2020 were reviewed. The impact of age on discharge outcomes was studied using multivariate analysis with generalized estimating equations adjusting for sex, race, NIHSS, time from onset to treatment, intravenous thrombolysis, and hospital-based characteristics (size, EVT volume, and stroke center certification), and region. Results: Among 8,344 EVT patients (mean age 71±15, 49% male), 32.9% were ≥ 80 years of age. Patients ≥ 80 years were more likely hypertensive (76% vs 63%), with atrial fibrillation (56% vs 26%), presented earlier to the hospital (onset to arrival 108 vs 126 min), with more severe strokes (NIHSS 17 (IQR=11) vs 15 (IQR=11)) and less likely to ambulate independently at baseline. Short term discharge outcomes and treatment complications, stratified by age ≥ 80 or &lt; 80 are shown in the Table. In multivariable analysis, elderly patients were less likely to achieve independent ambulation (OR: 0.37, CI 0.32, 0.43) and be discharged home/rehabilitation (OR 0.36, CI 0.33, 0.40). In the continuously adjusted model, for every year increase in age, the odds of independent ambulation decreased by 3% per year (p&lt;0.001) for patients 60-80 years of age and decreased by 7% for those over the age of 80. Discussion: In routine practice, one third of endovascularly treated LVO patients are over 80. Our data shows that EVT is safe in this population; however, age remains an independent predictor of poor discharge outcomes, especially in those over the age of 80.

Discordances Between Creatinine and Cystatin C-Based eGFR and Adverse Clinical Outcomes in Routine Clinical Practice

Discordances Between Creatinine and Cystatin C-Based eGFR and Adverse Clinical Outcomes in Routine Clinical Practice

Implementation of thyroid-related patient-reported outcomes in routine clinical practice.

Patient-reported outcomes (PROs) are increasingly used in clinical practice to improve clinical care. Multiple studies show that systematic use of PROs can enhance communication with patients and improve patient satisfaction, symptom management and quality of life. Further, such data can be aggregated to examine health levels for patient groups, improve quality of care, and compare patient outcomes at the institutional, regional or national level. However, there are barriers and challenges that should be handled appropriately to achieve successful implementation of PROs in routine clinical practice. This paper briefly overviews thyroid-related PROs, describes unsolved quality of life issues in benign thyroid diseases, provides examples of routine collection of PROs, and summarizes key points facilitating successful implementation of thyroid-related PROs in routine clinical practice. Finally, the paper touches upon future directions of PRO research.

Moving towards patient-reported outcomes in routine clinical practice: implementation lessons from the BREAST-Q.

PurposeLongitudinal, routine utilization of patient-reported outcome measures (PROMs) in clinical care has been challenging. The purpose of this study is to describe a quality improvement initiative to improve patient engagement with the BREAST-Q, a gold-standard PROM for breast reconstruction.MethodsIn 2011, we implemented the BREAST-Q as part of routine care. In 2018, we began a quality improvement initiative to increase BREAST-Q patient participation. The BREAST-Q was administered at every clinic visit via an institutional patient portal or an in-clinic tablet; digital dashboard technologies were used to improve workflow integration, real-time accountability, and immediate data availability at clinic visits. High clinical staff engagement was encouraged by assigning “BREAST-Q Champions.” BREAST-Q completion data and patient characteristics were examined to understand non-response to the assessment.ResultsFollowing quality improvement, the average annual BREAST-Q completion rate increased from 42.8% in 2011–2017 to 87.6% in 2019, the last full year of our study period. High completion rates were maintained January–July 2020; however, a significantly larger proportion of BREAST-Qs were completed at home in 2020 versus the same period in 2019 (49.7 vs. 38.8%, p < 0.001), potentially due to the COVID-19 pandemic. Compared with non-responders, responders were younger (49.7 vs. 52.2 years, p < 0.001), more likely to be white (76.9 vs. 73.6%, p < 0.001), and had private insurance (79.4 vs. 69.8%, p < 0.001).ConclusionOur quality improvement initiative successfully increased routine completion of the BREAST-Q. Similar implementation techniques may prove beneficial at other institutions interested in incorporating PROMs into routine care.

Real-world outcomes associated with bevacizumab combined with chemotherapy in platinum-resistant ovarian cancer.

5555 Background: In the pivotal Aurelia study, addition of bevacizumab (bev) to physician’s choice chemotherapy (paclitaxel, liposomal doxorubicin or topotecan) for platinum-resistant (PL-R) ovarian cancer (OC) was associated with improved progression-free survival (PFS; 6.7 vs 3.4 mos; hazard ratio (HR) 0.48, p = 0.001) but not overall survival (OS; 16.6 vs 13.3 mos HR 0.85, p = 0.174); the latter finding may relate to extensive crossover. In an exploratory subgroup analysis by treatment arm, benefits were particularly marked for bev + paclitaxel where median PFS (mPFS) increased from 3.9 to 10.4 mos (HR 0.46; 95%CI 0.30-0.71) and increases in OS approached statistical significance (HR 0.65; 95%CI, 0.42-1.02; 22.4 v 13.2 mos). Here we describe utilization of bev for PL-R OC and outcomes in routine clinical practice. Methods: The Ontario Cancer Registry and the New Drug Funding Program databases were utilized to identify all patients treated with bev plus chemotherapy (paclitaxel, liposomal doxorubicin or topotecan) for PL-R OC following its approval in 2017. Time on treatment (ToT) was defined as time from first to last bev treatment; this was used as a surrogate for PFS in routine practice. Median OS (mOS) was determined using the Kaplan-Meier method. Factors associated with ToT and OS were identified using a Cox proportional hazard model. A before and after comparison analysis was performed to determine mOS for patients treated pre- (2011-2017) and post-bev (2017-2019) approval. Results: From Oct 2017 to Dec 2019, 180 patients received bev + chemotherapy for first-line PL-R OC. Mean age was 63 years old, and 80% had serous OC. Bev was most often combined with liposomal doxorubicin (64 %) followed by paclitaxel (34%) and topotecan (2%). Median ToT was 3 months and OS was 11 months. ToT and OS were longer in patients who received paclitaxel as chemotherapy backbone (5 mos [ToT]; 14 mos [OS]) than those who received bev with liposomal doxorubicin (2 mos; 9 mos) or topotecan (2 mos; 6 mos). In multivariable models, ToT was superior in patients who received bev + paclitaxel than bev + liposomal doxorubicin (HR 0.40; 95%CI 0.28-0.57; p &lt; 0.0001), and worse with longer time from diagnosis to bev start (1.03; 1.01-1.05; p = 0.0120). OS was also significantly longer in those who received paclitaxel vs liposomal doxorubicin (HR 0.54; 95%CI 0.30-0.98; p = 0.043). In a before and after analysis, patients treated in the pre- (n = 1290) and post-bev (n = 360) era had mOS of 8 and 9 months respectively. Post mOS increased for patients receiving paclitaxel (7 vs 12 months) but not with liposomal doxorubicin (9 vs 7 months). Conclusions: ToT and OS associated with bev for PL-R OC are shorter in a real-world population compared to results reported in AURELIA. ToT and OS were longer with bev + paclitaxel than with other chemotherapy agents.