Physician Treatment Decisions Research Articles

BIOM-70. CSF TUMOR CELL (CSF-TC) DETECTION, QUANTIFICATION AND BIOMARKER ASSESSMENT HELPS IN CLINICAL MANAGEMENT OF BREAST CANCER AND NON-SMALL CELL LUNG CANCER PATIENTS HAVING LEPTOMENINGEAL DISEASE (FORESEE STUDY, NCT05414123)

Abstract Leptomeningeal metastases (LM) or the presence of cancer cells in the cerebrospinal fluid (CSF)/pia remains a challenging disease to diagnosis and treat. Current standard of care methods to diagnose or assess treatment response of LM (Clinical Evaluation, MRI and Cytology) have limited sensitivity and specificity and are poorly quantifiable. This creates challenges for physicians to manage LM or determine the best course of treatment. The FORESEE Study was a multi-center, prospective clinical trial evaluating a novel diagnostic platform, CNSide, that aimed to overcome these challenges. The FORESEE study enrolled patients with breast or non-Small Cell Lung Cancer (NSCLC) with suspicion of or confirmed LM. CNSide can detect and quantify tumor cells in the CSF from patients with breast cancer or NSCLC having a suspicious or confirmed LM. This platform also is able to identify actionable mutations in the CSF via Fluorescent In Situ Hybridization (FISH) and next-generation sequencing. The primary end point of the FORESEE study was clinical utility and the impact of CNSide on physician treatment decisions. Secondary endpoints included evaluating the clinical performance of CNSide vs. cytology in tumor cell detection (sensitivity, specificity, PPV and NPV). The study enrolled 40 patients (22 breast cancer and 18 NSCLC). Each patient underwent standard of care diagnostic evaluations at baseline and at three follow up timepoints through their treatment. CNSide aided clinical decision making in 93% (50/54) of the clinical decisions. At baseline 39 patients were assessed and confirmed a positive LM diagnosis in 15% (6/39), a negative LM diagnosis in 8% (3/39), progression in 15% (6/39), resolution in 15% (6/39) and no progression, or resolution in 36% (14/39) of the patients. CNSide informed the specific drug selected for treatment in 26% (10/39) patients at baseline and demonstrated clinical high utility. The FORESEE data is undergoing ongoing analysis; updated analysis will be presented at the meeting.

Fitting in? Physician practice style after forced relocation.

This study aims to examine how variation in physicians' treatment decisions for newborn deliveries responds to changes in the hospital-level norms for obstetric clinical decision-making. All hospital-based births in Florida from 2003 through 2017. Difference-in-differences approach is adopted that leverages obstetric unit closures as the source of identifying variation to exogenously shift obstetricians to a new, nearby hospital with different propensities to approach newborn deliveries less intensively. Births attributed to physicians continuously observed 2 years before the closure event and 2 years after the closure event (treatment group physicians) or for identical time periods around a randomly assigned placebo closure date (control group physicians). All of the physicians meeting our inclusion criteria shifted their births to a new hospital less than 20 miles from the hospital shuttering its obstetric unit. The new hospitals approached newborn births more conservatively, and treatment group physicians sharply became less aggressive in their newborn birth clinical management (e.g., use of C-section). The immediate 11-percentage point (33%) increase in delivering newborns without any procedure behavior change is statistically significant (p value <0.01) and persistent after the closure event; however, the physicians' payer and patient mix are unchanged. Obstetric physician behavior change appears highly malleable and sensitive to the practice patterns of other physicians delivering newborns at the same hospital. Incentives and policies that encourage more appropriate clinical care norms hospital-wide could sharply improve physician treatment decisions, with benefits for maternal and infant outcomes.

Abstract 16165: Implicit Bias and Unintentional Harm in Vascular Care: The Case for Intervention

Introduction. Unconscious, or implicit, bias may influence physician treatment decisions and contribute to healthcare disparities. Research Questions. Is implicit bias associated with inappropriate care for claudication and 1-year major amputation? Methods: All vascular interventionists of the Society for Vascular Surgery Vascular Quality Initiative (VQI) were invited to take the race Implicit Association Test (IAT). The IAT asks participants to classify sequential images of African American (Black) and European American (White) faces to positive and negative attributes and groups them by racial preference based on reaction time. IAT results were weighted and linked to VQI peripheral revascularization data to test the association between implicit bias with patient race and performance of below-knee procedures for claudication, a measure of inappropriate care. We assessed the association of below-knee procedures and patient race with odds of 1-yr amputation, using physician implicit bias as a moderator. Results: Among the 218 physicians that completed the IAT, physicians with White preference (70%) were more likely to perform a below-knee procedure on Black patients ( Fig A ) and their Black patients had increased odds of 1-yr amputation compared to White patients (OR: 3.0, 95%CI: 1.7-5.4). Physicians with no preference (20%) had no variability in below-knee procedures by patient race and fewer 1-yr amputations. A below knee procedure for claudication (ref: above-knee) was associated with increased odds of 1-year amputation, but the effect was greater among physicians with White bias (OR: 8.2;4.7-14.5) compared to no bias (OR: 3.6;1.4-9.7) ( Fig B ). Conclusions: Implicit bias is associated with inappropriate treatment selection, especially for Black patients. These results suggest the need for system level interventions that transparently identify procedures that are not aligned with best practices to reduce the negative effect of implicit bias.

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.

Obesity in adult acute myeloid leukemia is not associated with inferior response or survival even when dose capping anthracyclines: An ECOG-ACRIN analysis.

Obesity (body mass index [BMI] ≥30kg/m2 ) is an important epidemiological risk factor for developing acute myeloid leukemia (AML). Therefore, the authors studied the association of obesity with clinical and genetic phenotype and its impact on outcome in adults with AML. The authors analyzed BMI in 1088 adults who were receiving intensive remission induction and consolidation therapy in two prospective, randomized therapeutic clinical trials of the Eastern Cooperative Oncology Group-American College of Radiology Imaging Network: E1900 (ClinicalTrials.gov identifier NCT00049517; patients younger than 60years) and E3999 (ClinicalTrials.gov identifier NCT00046930; patients aged 60years or older). Obesity was prevalent at diagnosis (33%) and, compared with nonobesity, was associated with intermediate-risk cytogenetics group (p=.008), poorer performance status (p=.01), and a trend toward older age (p=.06). Obesity was not associated with somatic mutations among a selected 18-gene panel that was tested in a subset of younger patients. Obesity was not associated with clinical outcome (including complete remission, early death, or overall survival), and the authors did not identify any patient subgroup that had inferior outcomes based on BMI. Obese patients were significantly more likely to receive <90% of the intended daunorubicin dose despite protocol specification, particularly in the E1900 high-dose (90mg/m2 ) daunorubicin arm (p=.002); however, this did not correlate with inferior overall survival on multivariate analysis (hazard ratio, 1.39; 95% confidence interval, 0.90-2.13; p=.14). Obesity is associated with unique clinical and disease-related phenotypic features in AML and may influence physician treatment decisions regarding daunorubicin dosing. However, the current study demonstrates that obesity is not a factor in survival, and strict adherence to body surface area-based dosing is not necessary because dose adjustments do not affect outcomes.

Abstract P6-01-39: The impact of the 21-gene Recurrence Score® assay upon physician treatment recommendations in the neoadjuvant setting in lymph node-negative breast cancer patients in a multicenter prospective study in Quebec

Abstract Background: Although the role of the 21-gene Breast Recurrence Score® assay is well established to predict response to adjuvant chemotherapy in the setting of node-negative hormone receptor (HR)-positive, HER2-negative breast cancers (BC), fewer studies have evaluated the assay in the neoadjuvant setting. Due to the correlation between a high Recurrence Score® (RS) result and pathological complete response (pCR), the Breast Recurrence Score assay has been used to aid in selecting between chemotherapy (CT) or endocrine therapy. We wanted to further understand the impact of the assay upon physician treatment recommendations and the use of chemotherapy in this patient cohort. Methods: We conducted a multicenter, prospective, observational study in patients with clinically node-negative HR-positive, HER2-negative BC with T2-T3 disease being considered for neoadjuvant therapy. Physicians were required to complete two questionnaires indicating treatment choice, including CT, endocrine therapy, or surgery, prior to and post availability of RS result. Patients were followed up for 6 months after commencement of neoadjuvant therapy. The primary objective was to evaluate the change in the physician’s recommendation for neoadjuvant CT prior to and post assay results. As a secondary objective, we also evaluated the impact of the RS result on physician’s expressed level of confidence. Results: A total of 70 patients were enrolled between April 2018 and November 2021 at five hospital centers, as part of the McPeak Sirois Group of Quebec. The median age of the cohort was 60 years (range, 30 to 79 years). 24.3 % (n=17) of the cohort consisted of patients aged &amp;lt; 50 years, and 75.7% (n=53) were ≥ to 50 years. 29.0% (n=20) of the patients had a RS &amp;lt; 16, 39.1% (n=27) had a RS between 16-25, and 31.9% (n=22) had a RS &amp;gt; 25. For the entire cohort, the RS result led to a net reduction in chemotherapy recommendation by 33.3% (OR (odds of having CT post-RS recommendation versus pre-RS recommendation) = 0.23 [95% CI: 0.12-0.44]; P&amp;lt; 0.0001), and 39.2% net reduction in the use of chemotherapy at 6-month follow-up (OR = 0.18 [95% CI: 0.09-0.35]; P&amp;lt; 0.0001). Furthermore, the RS result led to a 35.3% net reduction in physician recommendation of CT for patients &amp;lt; 50 years (OR = 0.19 [95% CI: 0.04-0.83]; P=0.027) and a 32.7% net reduction for patients ≥ 50 years (OR = 0.24 [95% CI: 0.11-0.50]; P=0.0001). For patients with a RS &amp;lt; 16, there was a reduction in CT recommendation by 75.0%, and by 44.4% for patients with a RS between 16 - 25 (OR = 0.15 [95% CI: 0.06-0.38]; P&amp;lt; 0.0001). Moreover, RS results led to an increase in confidence in physician treatment decisions for 59.4% of patients (OR = 12.53 [95% CI: 5.46-28.78]; P&amp;lt; 0.0001). Conclusion: We determined that the 21-gene Breast Recurrence Score assay altered neoadjuvant treatment decisions, leading to a reduction in the use of chemotherapy by about one-third, regardless of age. Additionally, the assay increased physician confidence in their treatment recommendation for about 60% of patients. This demonstrates the potential clinical utility of the assay to decrease the use of CT in the neoadjuvant setting amongst HR-positive, node-negative BC patients in Quebec. Citation Format: Mariya Yordanova, Lucas Sideris, Pierre Dubé, Jean-Francois Boileau, Julie Lemieux, Catalin Mihalcioiu, Sylvie Levesque, Marie-Claude Guertin, Erica Patocskai, Rami Younan, André Robidoux, Saima Hassan. The impact of the 21-gene Recurrence Score® assay upon physician treatment recommendations in the neoadjuvant setting in lymph node-negative breast cancer patients in a multicenter prospective study in Quebec [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P6-01-39.

A Matching-adjusted Indirect Comparison of Nivolumab Plus Cabozantinib Versus Pembrolizumab Plus Axitinib in Patients with Advanced Renal Cell Carcinoma

BackgroundThe comparative efficacy and health-related quality of life (HRQoL) outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib as first-line treatments for advanced renal cell carcinoma (aRCC) have not been assessed in head-to-head trials. ObjectiveTo assess the efficacy and HRQoL outcomes of nivolumab plus cabozantinib versus pembrolizumab plus axitinib. Design, setting, and participantsPatient-level data for nivolumab plus cabozantinib from the CheckMate 9ER trial and published data for pembrolizumab plus axitinib from the KEYNOTE-426 trial were used. CheckMate 9ER data were reweighted to match the key baseline characteristics as reported in KEYNOTE-426. InterventionNivolumab (240 mg every 2 wk) plus cabozantinib (40 mg once daily) and pembrolizumab (200 mg every 3 wk) plus axitinib (5 mg twice daily, initially). Outcome measurements and statistical analysisHazard ratios (HRs) for progression-free survival (PFS), duration of response, overall survival (OS), and deterioration in HRQoL were assessed using weighted Cox proportional-hazard models, with sunitinib as a common anchor. Objective response rates (ORRs) and changes in HRQoL scores from baseline were assessed as difference-in-differences for the two treatments relative to sunitinib. Results and limitationsAfter balancing patient characteristics between the trials, nivolumab plus cabozantinib was associated with significantly improved PFS (HR [95% confidence interval {CI}] 0.70 [0.53–0.93]; p = 0.01) and a significantly decreased risk of confirmed deterioration in HRQoL (Functional Assessment of Cancer Therapy—Kidney Symptom Index—Disease-related Symptoms: HR [95% CI] 0.48 [0.34–0.69]) versus pembrolizumab plus axitinib. OS was similar between treatments (HR [95% CI] 0.99 [0.67–1.44]; p = 0.94). Nivolumab plus cabozantinib was associated with numerically greater ORRs (difference-in-difference [95% CI] 8.4% [–1.7 to 18.4]; p = 0.10) and longer duration of response (HR [95% CI] 0.79 [0.47–1.31]; p = 0.36) than pembrolizumab plus axitinib. Comparative studies using data with a longer duration of follow-up are warranted. ConclusionsNivolumab plus cabozantinib significantly improved PFS and HRQoL compared with pembrolizumab plus axitinib as first-line treatment for aRCC. Patient summaryThis study was conducted to indirectly compare the results of two immunotherapy-based combinations—nivolumab plus cabozantinib versus pembrolizumab plus axitinib—for patients who have not received any treatment for advanced renal cell carcinoma. Patients who received nivolumab plus cabozantinib had a significant improvement in the length of time without worsening of their disease and in their perceived physical and mental health compared with pembrolizumab plus axitinib; patients remained alive for a similar length of time from the start of either treatment. This analysis further adds to our current knowledge of the relative benefits of these two treatment regimens and will help with physician and patient treatment decisions.

The Effect of Surgeon Referral and a Radiation Oncologist Productivity-Based Metric on Radiation Therapy Receipt Among Elderly Women With Early Stage Breast Cancer: Analysis From a Tertiary Cancer Network

PurposeGuidelines for early-stage breast cancer allow for radiation therapy (RT) omission after breast conserving surgery among older women, though high utilization of RT persists. This study explored surgeon referral and the effect of a productivity-based bonus metric for radiation oncologists in an academic institution with centralized quality assurance review. Methods and MaterialsWe evaluated patients ≥70 years of age treated with breast conserving surgery for estrogen receptor (ER)+ pT1N0 breast cancer at a single tertiary cancer network between 2015 and 2018. The primary outcomes were radiation oncology referral and RT receipt. Covariables included patient and physician characteristics and treatment decisions before versus after productivity metric implementation. Univariable generalized linear effects models explored associations between these outcomes and covariables. ResultsOf 703 patients included, 483 (69%) were referred to radiation oncology and 273 (39%) received RT (among those referred, 57% received RT). No difference in RT receipt pre- versus post-productivity metric implementation was observed (P = .57). RT receipt was associated with younger patient age (70-74 years; odds ratio [OR], 2.66; 95% confidence interval [CI], 1.54-4.57) and higher grade (grade 3; OR, 7.75; 95% CI, 3.33-18.07). Initial referral was associated with younger age (70-74; OR, 5.64; 95% CI, 3.37-0.45) and higher performance status (Karnofsky performance status ≥90; OR, 5.34; 95% CI, 2.63-10.83). ConclusionsNonreferral to radiation oncology accounted for half of RT omission but was based on age and Karnofsky performance status, in accordance with guidelines. Lack of radiation oncologist practice change in response to misaligned financial incentives is reassuring, potentially reflecting incentive design and/or centralized quality assurance review. Multi-institutional studies are needed to confirm these findings.

Impact of the 21-Gene Recurrence Score Assay on Treatment Decisions and Cost in Patients with Node-Positive Breast Cancer: A Multicenter Study in Quebec.

BackgroundThe 21-gene Breast Recurrence Score (RS) assay, “the assay”, has led to a paradigm shift for patients with hormone receptor-positive, node-negative early breast cancer and is emerging as an important tool to assist physician-patient decisions in foregoing chemotherapy in node-positive patients. We wanted to better understand the impact of the RS assay in node-positive patients upon physician treatment decisions and treatment cost in Quebec, Canada.Patients and MethodsWe conducted a multicenter, prospective observational trial for Estrogen/Progesterone Receptor (ER/PR)- positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer patients with 1-3 positive lymph nodes. Physicians completed a questionnaire indicating treatment choice prior to and post availability of RS results. The primary endpoint was change in the physician’s recommendation for chemotherapy prior to and post assay results. Secondary endpoints included change in physician’s expressed level of confidence, and changes in estimated cost of recommended treatments prior to and post assay results.ResultsFor the entire cohort, physician recommendation for chemotherapy was reduced by an absolute 67.1% by knowledge of the RS assay result (P < .0001). Physician recommendation of chemotherapy was decreased by 75.9% for patients RS result <14 (P < .0001); and 67.5% for patients with RS result 14-25 (P < .0001). Changes in treatment recommendations were associated with an overall reduction in cost by 73.7% per patient, and after incorporating the cost of the RS test, a cost benefit of $823 CAN at 6-month follow-up.ConclusionAltogether, we established that the assay led to a two-third reduction in the use of chemotherapy, and was a cost-effective approach for hormone receptor-positive, node-positive breast cancer.

The Role of the 21-Gene Recurrence Score® Assay in Hormone Receptor-Positive, Node-Positive Breast Cancer: The Canadian Experience.

The management of patients with hormone receptor-positive breast cancer has changed dramatically with use of the 21-gene Recurrence Score® (RS) Assay. While the utility of the assay was initially demonstrated among node-negative patients, recent studies have also demonstrated the assay’s prognostic and predictive value in node-positive patients. In Canada, the RS assay is reimbursed by provincial health insurance plans, but not all provinces have approved the use of the assay for patients with node-positive disease. Here, we provide an overview of the clinical factors that influence physician recommendation of the RS assay and, alternatively, the impact of the RS assay on patient treatment decisions in Canada. We performed a comprehensive review of the impact of the assay upon physician treatment decisions and cost in node-positive breast cancer patients within Canada and other countries. Furthermore, we evaluated biomarkers that can predict the RS result, in addition to other genomic assays that predict recurrence risk among node-positive patients. Overall, the 21-gene RS assay was shown to be a cost-effective tool that significantly reduced the use of chemotherapy in node-positive breast cancer patients in Canada.

Neglected geriatric assessment and overtreatment of older patients with pancreatic cancer - Results from a prospective phase IV clinical trial

BackgroundOlder patients with metastatic pancreatic cancer may suffer increased toxicity from intensive chemotherapy. Treatment individualization by geriatric assessment (GA) might improve functional outcome. MethodsWe performed a multicenter, phase IV, open label trial in patients ≥70 years with metastatic pancreatic adenocarcinoma. Patients underwent GA and were assigned to one of three categories based on their scores: Go-Go, Slow-Go, or Frail. These categories were intended to guide physician's treatment decisions when choosing to treat patients with nab-paclitaxel/gemcitabine (arm A), gemcitabine (arm B), or best supportive care (arm C). Primary objective was a stable (loss of five points or less) Barthel's Activities of Daily Living (ADL) score during chemotherapy; secondary endpoints included GA scores during therapy, safety, quality of life, response and survival rates. ResultsThirty-two patients were enrolled in the trial in six centers in Germany (out of 135 planned), resulting in termination due to low recruitment. Fifteen patients were allocated to nab-paclitaxel/gemcitabine, fifteen to gemcitabine, and two to best supportive care by their physicians, although according to their GA scores 29 patients (91%) were categorized as Slow-Go and three (9%) as Go-Go. Thus, fifteen of 32 (47%) patients were misclassified and given a course of treatment inconsistent with their GA scores. Median progression-free survival (PFS) were 3.3 months and 9.1 months and median time to quality-of-life deterioration 13 days and 29 days in the nab-paclitaxel/gemcitabine and gemcitabine monotherapy arms, respectively. Serious adverse events were reported in 11 (78.6%) patients in the nab-paclitaxel/gemcitabine and 8 (53.3%) patients in the gemcitabine arm. ConclusionsClinical evaluations by investigators differed markedly from geriatric assessments, leading to potential overtreatment. In our modest sample size study, those patients undergoing more intensive therapy had a less favorable course.

Alternative payment models and physician treatment decisions: Evidence from lower back pain

The capitated payment model has been used to address the high cost of health care. Under capitation, physicians are compensated with a fixed amount per patient, regardless of the services generated. We provide new evidence on how the capitation payment model changes physicians behaviors by studying the treatment of lower back pain, as this type of treatment provides substantial scope for physicians discretion. We use data from 2003 to 2006 from a large database of employer-sponsored health insurance claims and leverage capitation variation within the plan and physician to mitigate selection concerns. The results show that the treatment intensity—primarily derived from therapy and diagnostic testing —of patients under a capitation system is 7–12% lower than that of similar patients in a non-capitated plan. Furthermore, we find no evidence of increased relapse rates for patients in a capitated plan.

Abstract PS4-27: A prospective multicenter study evaluating the impact of the 21-Gene Breast Recurrence Score® upon physician treatment decision and cost in lymph node-positive breast cancer patients in Quebec

Abstract Background: Locoregional lymph node involvement has historically been used as the most important deciding factor for the administration of chemotherapy in the adjuvant setting of breast cancer patients. The 21-gene Breast Recurrence Score® assay (the assay) is emerging as an important tool to assist with chemotherapy decisions amongst hormone receptor (HR)-positive, node-positive breast cancer (BC) patients. Previous studies have suggested that node-positive patients with low Recurrence Score (RS) results do not benefit from chemotherapy. We wanted to better understand the impact of the assay upon physician treatment decisions and treatment cost in this patient cohort. Methods: We conducted a multicenter prospective observational trial for ER/PR-positive HER2-negative BC patients that have undergone surgical treatment for T1-T3 disease and 1-3 positive lymph nodes. Physicians were required to complete a questionnaire indicating treatment choice prior to and post availability of Recurrence Score results. Patients were enrolled in the study from the time of consent to 6 months after the start of adjuvant therapy. The primary endpoint was change in the physician’s recommendation for chemotherapy prior to and post assay results. Secondary endpoints include the change in recommendation for additional growth factor (GF) supportive therapy, change in physician’s expressed level of confidence, and changes in estimated cost of recommended treatments prior to and post assay results. Results: 70 patients were enrolled between March 2018 and September 2019 at five hospital centers, as part of the McPeak Sirois Group of Quebec. The median age of the cohort was 61 years (range, 38 to 82 years). 18.5% (n=13) of the cohort consisted of patients &amp;lt; 50 years, and 81.4% (n=57) were &amp;gt; or = to 50 years. 64.3% (n=45) of the patients had one positive lymph node and 35.7% (n=25) of the patients had 2 or 3 positive lymph nodes. 25.7% (n=18) of the patients had a RS &amp;lt; 11 and 68.6% (n=48) had a RS result between 11-25. For the entire cohort, we found that the proportion of patients for whom chemo-hormonal therapy was recommended was reduced by an absolute 67.1% by knowledge of the RS result (OR (odds of having chemo-hormonal therapy post-RS recommendation versus pre-RS recommendation) = 0.03 [95% CI: 0.01-0.08]; P&amp;lt;0.0001). The RS results led to an absolute reduction in physician recommendation in chemo-hormonal therapy by 38.5% for patients &amp;lt; 50 years, and by 73.7% of patients (OR=0.02 [95% CI: 0.01-0.06]; P &amp;lt;0.0001) for patients &amp;gt; or = to 50 years. Changes in treatment recommendation were identified for patients with one positive node, 73.3% (OR=0.02 [95% CI: 0.01-0.07]; P&amp;lt;0.0001); and for patients with two or three positive nodes, 56.0% (OR=0.06 [95% CI: 0.02-0.23]; P&amp;lt;0.0001). Recommendations for GF supportive therapy due to RS results decreased by 42.6% (OR=0.16 [95% CI: 0.07-0.34]; P &amp;lt;0.0001). Moreover, RS results led to an increase in confidence in physician treatment decisions for 68.6% of patients (OR=18.3 [95% CI: 7.90-42.28]; P &amp;lt;0.0001). We found that the cost of chemotherapy, in addition to anti-emetics and GF supportive therapy, decreased by 69.9% per patient (pre-RS mean, $3,968 CAN; versus post-RS mean, $1,196 CAN) (P &amp;lt;0.0001). Conclusions: Overall, we found that the 21-gene Breast Recurrence Score® assay changed physician treatment decisions in about two-thirds of all patients with hormone receptor-positive, node-positive BC, regardless of the number of positive nodes (up to 3). The assay increased physician confidence and was associated with an important decrease in treatment cost. Taken together, the assay is a cost-effective approach that can decrease the use of chemotherapy amongst HR-positive, node-positive BC patients in Quebec. Citation Format: Saima Hassan, Rami Younan, Erica Patocskai, Louise Provencher, Brigitte Poirier, Lucas Sideris, Pierre Dubé, Jean-Francois Boileau, Catalin Mihalcioiu, André Robidoux. A prospective multicenter study evaluating the impact of the 21-Gene Breast Recurrence Score® upon physician treatment decision and cost in lymph node-positive breast cancer patients in Quebec [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS4-27.

On using electronic health records to improve optimal treatment rules in randomized trials.

Individualized treatment rules (ITRs) tailor medical treatments according to patient-specific characteristics in order to optimize patient outcomes. Data from randomized controlled trials (RCTs) are used to infer valid ITRs using statistical and machine learning methods. However, RCTs are usually conducted under specific inclusion/exclusion criteria, thus limiting their generalizability to a broader patient population in real-world practice settings. Because electronic health records (EHRs) document treatment prescriptions in the real world, transferring information in EHRs to RCTs, if done appropriately, could potentially improve the performance of ITRs, in terms of precision and generalizability. In this work, we propose a new domain adaptation method to learn ITRs by incorporating information from EHRs. Unless we assume that there is no unmeasured confounding in EHRs, we cannot directly learn the optimal ITR from the combined EHR and RCT data. Instead, we first pretrain "super" features from EHRs that summarize physician treatment decisions and patient observed benefits in the real world, as these are likely to be informative of the optimal ITRs. We then augment the feature space of the RCT and learn the optimal ITRs by stratifying by super features using subjects enrolled in RCT. We adopt Q-learning and a modified matched-learning algorithm for estimation. We present heuristic justification of our method and conduct simulation studies to demonstrate the performance of super features. Finally, we apply our method to transfer information learned from EHRs of patients with type 2 diabetes to learn individualized insulin therapies from RCTdata.

The effect of Nigella sativa (black cumin seeds) and Zingiber officinale (Ginger rhizome) Essential Oils on Multidrug-Resistant Bacteria

Antibiotic resistance is growing and has limited the ability of physician's treatment decisions. Discovery of new, effective and safe substances that prevent troublesome infections is greatly needed to provide alternative therapeutic options. This study evaluated the antibacterial and synergistic effect of Hydro extracts of two plants essential oils of black seed (Nigella sativa) and ginger (Zingiber officinale) rhizome each alone and in combination, against selected different strains of gram negative and gram positive multidrug-resistant bacteria (Klebsiella pneumonia, Acinetobacter baumannii, Pseudomonas aeruginosa , Escherichia coli and Methicillin Resistant Staphylococcus aureus ) isolated from burn patients. The isolated were identified basing upon their colony characteristics, gram-staining, motility and biochemical tests according to standard microbiological techniques. All the isolates were tested for their susceptibility to different antibiotics and compared to the interpretive chart zone sizes. The antibacterial effect of essential oils was conducted against all isolates by disk diffusion assay, the minimum inhibitory concentrations and the minimum bactericidal concentrations of the plant essential oils were processed by using micro-dilution technique. The results indicated that all the different strains of Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Escherichia coli that were tested against 100% concentration of essential oils; there was no recorded zone of inhibition. However, for the different strains of Methicillin Resistant Staphylococcus aureus, different zones of inhibition where obtained for Nigella sativa oil singly and combination of Nigella sativa with Zingiber officinale at different dilutions 100%, 75%, 50%, 25%, 12.5%, 6.25% and 3.12%. Nigella sativa oil alone presents inhibition zones at concentration 100% ranged between (10mm) to (34mm), while Zingiber officinale oil extracts alone had no significant antibacterial effect. In &#x0D; addition, combination of both oil extracts at 100% concentration showed inhibition zone greatest than the standards antibiotics which ranged between (12mm) to (52mm). Synergistic effect was noticed in combination of Nigella sativa, Zingiber officinale oil extracts and Antibiotics. The combination of both oil extracts of Nigella sativa oil and Zingiber officinale oil showed an excellent antibacterial and synergistic activity against Methicillin Resistant Staphylococcus aureus.

Abstract P6-13-04: IMPACt trial: MammaPrint and BluePrint molecular subtyping guide treatment decisions in breast cancer

Abstract Background: IMPACt is a prospective, case-only study to measure the effect of MammaPrint (MP) and BluePrint (BP) on treatment decisions in breast cancer patients. Here, we report the results of the primary objective in women aged ≥18 years with histologically proven invasive stage I-II, hormone receptor (HR) positive, and HER2-negative breast cancer. Methods: The study included 369 women from 18 US institutions. The recommended treatment plan was captured before and after receiving results for MP and BP. Treatment was started after obtaining results. In addition to the effect of results on physician treatment decisions involving chemotherapy (CT) and physician confidence, the distribution of MP High Risk (HR) and Low Risk (LR) patients was also evaluated. Results: MP classified patients to 62% (n=228) LR and 38% (n=141) HR. Treatment decisions were changed for 25% (n=92) of women after receiving MP and BP results. Of the LR patients initially prescribed CT, 68% (45/66) had CT removed from their treatment recommendation. Of the HR patients who initially were not prescribed CT, 66% (42/64) had CT added. Overall, 89% (202/228) of LR patients did not receive CT, and likewise 84% (119/141) of HR patients did receive CT after receiving MP. Among those who did not change treatment (n=277), 68% of physicians reported having greater confidence in their prescribed therapy. Conclusions: The IMPACt trial shows MP generates a 25% overall treatment change in clinical practice. The highest impact is for women with LR results, where 68% are spared chemotherapy in favor of endocrine therapy alone. Additionally, 73% of physicians report having higher confidence in treatment decisions for their patient after MP. Table 1: Treatment changesTreatment Decision Pre- to Post-MPMP HRMP LRTotalCT to CT772198no CT tp CT42547CT to no CT04545no CT to no CT22157179Total141228369 Citation Format: Soliman H, Rehmus E, Shah V, Srkalovic G, Mahtani R, Levine E, Mavromatis B, Srinivasiah J, Kassar M, Gabordi R, Yoder E, Qamar R, Audeh W, IMPACt Investigators Group I. IMPACt trial: MammaPrint and BluePrint molecular subtyping guide treatment decisions in breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P6-13-04.

Abstract P2-10-07: A prospective clinical utility study of the impact of the 21-gene recurrence score (RS) assay in the treatment of estrogen receptor positive (ER+), HER2 negative (HER2-), 1-3 node positive (N+) breast cancer (BC)

Abstract Background: The 21-gene RS is routinely used in node negative ER+, HER2- BC to help guide chemotherapy treatment decision making. There is emerging use of the RS in limited N+ BC, though the results from the randomized clinical trial (RxPONDER) is pending. The objective of the study is to determine whether the results of the 21-gene RS will alter physician treatment decisions in ER+ HER2- limited N+ BC. Methods: Consenting patients (pts) with ER+, HER2-, 1-3 N+ (microscopic or macroscopic) early stage BC participated in this prospective, multi-center British Columbia Cancer Agency (BCCA) study. Treating physicians completed a questionnaire after an initial visit with the patient to document their treatment recommendation before obtaining the RS assay. At a subsequent visit, the assay result and final treatment recommendations were discussed and physicians completed a second questionnaire on the final treatment plan. The statistical assumption of the study was based upon anticipating an overall treatment decision change rate (from chemo-hormonal therapy to hormone only, or vice-versa) to be at least 30%. Results: Out of 84 pts enrolled, 82 went on to have RS testing. 57% of pts had T1 tumors, 40% T2 and 2% T3 tumors. The majority of pts (77%) had N1 macroscopic disease compared to 23% that had microscopic nodal involvement. 63% of cases were grade 2, followed by 23% grade 1 and 14% grade 3. 60% of RS were low (&amp;lt;18), 33% intermediate (18-30) and 7% were high (&amp;gt;30). In 53% of cases there was an altered treatment plan (49% switched from chemo-hormonal therapy to hormone only, and 4% switched from hormone only to chemo-hormonal therapy). Of the 49% that switched to hormone only, 68% had a low RS and 33% had an intermediate RS. All 4% that switched to chemo-hormonal therapy had an intermittent RS. Conclusions: This multi-centered Canadian study showed that in 53% of cases, treatment recommendations were changed based on the RS. This suggests that there is clinical utility for the RS in 1-3 N+, ER+, and HER2- breast cancer. Citation Format: Sun J, Fenton D, Baxter S, Chan A, Roberts S, Feng X, Lohrisch C, Gelmon K, Shenkier T, Chia S. A prospective clinical utility study of the impact of the 21-gene recurrence score (RS) assay in the treatment of estrogen receptor positive (ER+), HER2 negative (HER2-), 1-3 node positive (N+) breast cancer (BC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-10-07.

Patient factors in decision-making for orthopaedic surgery: a prospective analysis

Background: Previous research on surgical decision-making is inconsistent regarding the relative importance of patient and surgeon preferences for treatment. Few studies have related clinical indicators and patients’ inherent attitudes to subsequent physician recommendations and treatment decisions. In this study we evaluated the influence of a patient’s baseline attitudes and clinical factors on the patient’s intention for surgery, the physician’s recommendation about surgery, and ultimate surgical decision-making. Methods: Patients with musculoskeletal pain (N=202) were assessed for clinical indicators of surgery and attitudinal variables before their initial surgical consultation. Logistic regressions analyzed how baseline variables subsequently predicted surgeon’s recommendations and whether or not the patient had surgery, and compared the relative importance of the predictors. We also examined which variables predicted adherence to surgeon’s recommendations. Results: Higher baseline pain, disability, knowledge of risks, and family encouragement for surgery positively predicted the patient’s intention to have surgery, which, in turn, was the strongest predictor of the surgeon’s recommendation. Both surgeon’s recommendation and patient’s baseline intention for surgery jointly predicted final treatment decisions. In addition, patient’s intention for surgery was the only predictor of whether or not patients adhered to their surgeon’s recommendation. Conclusions: Patients may form strong opinions about surgery before consulting a surgeon, and these opinions impact the physician’s recommendation and ultimate treatment decisions, sometimes leading patients to act inconsistently with their surgeon’s recommendation. These findings help clarify the influence that patients have in treatment decision-making and highlight the importance of recognizing the critical role of patients’ backgrounds in elective surgery.

Guideline Adherence Regarding the Use of Expensive Drugs in Daily Practice: The Examples of Trastuzumab in Breast Cancer and Bortezomib in Multiple Myeloma

Background: The present study was designed to obtain insights into guideline adherence regarding the use of expensive drugs in The Netherlands in daily practice and into the patients' perspective on the decision-making process. Material and Methods: A retrospective review of medical charts regarding the use of trastuzumab in early and metastatic breast cancer (EBC/MBC) and bortezomib in multiple myeloma (MM) was conducted. Prescription according to clinical practice guidelines was assessed. The review was supplemented with patient interviews. Results: Of 702 adjuvant-treated EBC patients, 97% had a documented human epidermal growth factor receptor 2 (HER2) testing (23% HER2 positive). 92% (147/160) of the HER2-positive EBC patients were treated with trastuzumab. Of 594 MBC patients, 81% had a documented HER2 testing (19% HER2 positive). 82% (75/91) of the HER2-positive MBC patients were treated with trastuzumab. Of 68 MM patients, 50% were treated with bortezomib. Reasons not to treat were consistent with the guidelines. Patients were generally satisfied with the decision-making process; improvements in patient education were suggested (e.g., repeating the information given, adding information on side effects). Conclusions: Guidelines were generally well followed with respect to trastuzumab and bortezomib, indicating that funding did not influence the treatment decisions of physicians. In view of the growing numbers of both cancer patients and expensive new anticancer drugs, and increasing budget constraints, it is unclear whether the present-day policies will guarantee a similar level of guideline adherence. Patient involvement in decision-making could be increased by improving the patient education on treatment.

Analyzing the "CareGap": assessing gaps in adherence to clinical guidelines in adult soft tissue sarcoma.

Clinical decision support systems (CDSSs) are gaining popularity as tools that assist physicians in optimizing medical care. These systems typically comply with evidence-based medicine and are designed with input from domain experts. Nonetheless, deviations from CDSS recommendations are abundant across a broad spectrum of disorders, raising the question as to why this phenomenon exists. Here, we analyze this gap in adherence to a clinical guidelines-based CDSS by examining the physician treatment decisions for 1329 adult soft tissue sarcoma patients in northern Italy using patient-specific parameters. Dubbing this analysis "CareGap", we find that deviations correlate strongly with certain disease features such as local versus metastatic clinical presentation. We also notice that deviations from the guideline-based CDSS suggestions occur more frequently for patients with shorter survival time. Such observations can direct physicians' attention to distinct patient cohorts that are prone to higher deviation levels from clinical practice guidelines. This illustrates the value of CareGap analysis in assessing quality of care for subsets of patients within a larger pathology.