Citations

Abstract Introduction: There is evidence that lack of a social network is a link to inferior outcomes in cancer patients. Mayo clinic performs all its stem cell transplants for multiple myeloma patients as an outpatient. This requires a full-time chaperone or caregiver for the duration of the transplant. Patients who do not have a caregiver are hospitalized for the duration of the transplant. In this study we compared outcomes between patients hospitalized for the entire transplant and those who have a caregiver and are initially managed as an outpatient.Materials and methods: All patients with multiple myeloma transplanted at the Mayo Clinic in Rochester Minnesota between 1/1/2000 and 12/31/2019 were included for analysis. Patient had to have been transplanted within 12 months of the original diagnosis. The definition of inpatient transplantation was hospitalization prior to day 0 of transplantation for conditioning and continued hospitalization until evidence of neutrophil engraftment occurred.Results: There were 41 patients who were considered inpatient transplants and 2103 that were outpatient transplants. The patients were well balanced for age, sex, serum creatinine, and international stage at diagnosis. For inpatient transplants the median days in the hospital was 21 (interquartile range 18 to 28). For outpatient transplants the median number of days in the hospital was 0 (interquartile range 0 to 6). Relapse free survival was not significantly different between the 2 groups, but overall survival was 95 versus 58 months favoring those that had transplantation as an outpatient (p=.0008). Conclusion: There appears to be in association between myeloma patients that lack a caregiver and require inpatient stem cell transplantation and overall survival.

Background: Careful selection of patients with expiratory central airway collapse (ECAC) that may benefit from tracheobronchoplasty (TBP) can be aided by a short-term airway stent evaluation. This can be performed with either silicone Y-stents (SYSs) or uncovered self-expanding metallic airway-stents (USEMAS). No direct comparison has been made between these 2 stent types. Methods: This was a small retrospective review of consecutive patients that underwent a stent evaluation. A propensity score was used to match patients in the USEMAS and SYS groups. Outcomes included complications, changes in the health-related quality-of-life (HR-QoL), and changes in exercise capacity. Baseline measurements were compared with those obtained during stent evaluation and after TBP. Results: Forty-two patients with severe ECAC underwent USEMAS placement, while 18 patients had an SYS placed. Propensity score matching resulted in 13 matched SYS and USEMAS pairs. The SYS group had an increased rate of mucus plugging (38.5% vs. 0%, P<0.047). Although not statically significant, a clinical improvement was observed in HR-QoL and exercise capacity in the USEMAS group during stent placement. In patients who underwent TBP, both USEMAS and SYS groups had a statistically significant change in the Modified Medical Research Council Dyspnea Scale during stent evaluation and after TBP. Conclusion: In patients with severe ECAC, short-term evaluation with airway stents appears to be safe and improves respiratory symptoms, HR-QoL, and exercise capacity. The use of USEMAS led to a lower complication rate, a greater improvement in HR-QoL and exercise capacity, and appeared to better predict how the patients would respond to TBP.

AbstractBackgroundGuidelines include several options for average‐risk colorectal cancer (CRC) screening that vary in aspects such as invasiveness, recommended frequency, and precision. Thus, patient and provider preferences can help identify an appropriate screening strategy. This study elicited CRC screening preferences of physicians and individuals at average risk for CRC (IAR).MethodsIAR aged 45–75 years and licensed physicians (primary care or gastroenterology) completed an online discrete choice experiment (DCE). Participants were recruited from representative access panels in the US. Within the DCE, participants traded off preferences between screening type, screening frequency, true‐positive, true‐negative, and adenoma true positive (physicians only). A mixed logit model was used to obtain predicted choice probabilities for colonoscopy, multi‐target stool DNA (mt‐sDNA), fecal immunochemical test (FIT), and methylated septin 9 (mSEPT9) blood test.ResultsPreferences of IAR and physicians were affected by screening precision and screening type. IAR also valued more regular screening. Physicians preferred colonoscopy (96.8%) over mt‐sDNA (2.8%; p < 0.001), FIT (0.3%; p < 0.001) and mSEPT9 blood test (0.1%; p < 0.01). IAR preferred mt‐sDNA (38.8%) over colonoscopy (32.5%; p < 0.001), FIT (19.2%; p < 0.001), and mSEPT9 blood test (9.4%; p < 0.001). IAR naïve to screening preferred non‐invasive screening (p < 0.001), while the opposite was found for those who previously underwent colonoscopy or sigmoidoscopy.ConclusionsWhile physicians overwhelmingly preferred colonoscopy, preferences of IAR were heterogenous, with mt‐sDNA being most frequently preferred on average. Offering choices in addition to colonoscopy could improve CRC screening uptake among IAR.This study used a discrete choice experiment in the US to elicit preferences of physicians and individuals at average risk for colorectal cancer screening modalities and their characteristics.

Introduction: The incidence of heart failure (HF) is higher in black than in white Americans, but the causes are unclear. We proposed that ethnic differences in ventricular-arterial interaction may contribute to this differential HF risk. Methods: We studied measures of arterial elastance (Ea) and left ventricle (LV) end-systolic elastance (Ees) in 5767 community-based elderly participants (76±5 years, 41% male, 22% black) who underwent echocardiography in the Atherosclerosis Risk in Community (ARIC) Study. Results: Black participants were more frequently women (66 vs 57%) and had a higher prevalence of obesity (46 vs 31%), hypertension (94 vs 80%), and diabetes mellitus (47 vs 34%). Adjusting for these baseline differences, the prevalence of LV hypertrophy was similar, but Ea, Ees and Ea/Ees ratio were higher in blacks than whites, particularly in black women (Figure). Ea was positively associated with LV mass index and E/e’ ratio in blacks, but not in whites (p for interaction < 0.001). Conclusion: These community-based data demonstrate that ventricular-arterial stiffening is greater in black than white Americans, coupled with more ventricular remodeling and dysfunction. The heightened afterload dependence in blacks suggests greater potential for risk reduction with anti-hypertensive therapy.

Background: The 2013 ACC/AHA Cholesterol Guidelines departed from prior ATPIII guidelines, recommending statin treatment based on patients’ predicted 10-year ASCVD risk and de-emphasizing LDL-C targets. However, the degree to which these new guidelines have been adopted by clinicians in community practice is unknown. Methods: We surveyed 522 clinicians in 133 cardiology, primary care, and endocrinology practices participating in the Patient and Provider Assessment of Lipid Management (PALM) Registry. Clinicians were asked about their likelihood of prescribing statins in 4 hypothetical patient scenarios. Results: Among responders, 79% were physicians (60% cardiologists, 38% primary care or general practice, 2% endocrinology), 18% were advanced practice providers, and 3% trainees. When queried, 73% of providers reported primarily using the 2013 ACC/AHA Guidelines to guide lipid management. However, only half reported “often” or “always” calculating 10-year ASCVD risk to aid lipid management decisions for primary prevention. When presented with a high 10-year ASCVD risk patient (>15%) with a high LDL-C (150 mg/dL), 92% of providers recommended statins. Similarly, 83% of providers would use statins in a diabetic patient with a LDL-C of 140 mg/dL. Yet, only 37% reported they would prescribe a statin to an older adult (age 70) for whom guidelines recommend statin based on high 10-year ASCVD risk alone (10.1%). And up to 40% would prescribe a statin to a younger (age 40) with a low 10-year risk, but a high LDL (165 mg/dL) who would not otherwise meet criteria for statin therapy under the new guidelines. Cardiologists and non-cardiologists were similarly likely prescribe statins in most scenarios with the exception of to the younger patient with elevated LDL-C were cardiologists used statins more commonly (32% vs. 42%. OR 1.5, 95% CI 1.1-2.2, p=0.02). Conclusion: Initial survey results show that while most clinicians claim adoption of the 2013 ACC/AHA Guidelines, reported practices are not always adherent to these guidelines. Providers do not always calculate 10-year ASCVD risk to guide lipid management and many do not prescribe statins to patients eligible based on 10-year ASCVD risk.

Abstract Background: I-SPY 2 is a multicenter, phase 2 trial using response-adaptive randomization within molecular subtypes defined by receptor status and MammaPrint (MP) risk to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. Tucatinib is a potent HER2 (ErbB2) tyrosine kinase inhibitor, selective for HER2 vs. epidermal growth factor receptor (EGFR) and is active vs. brain metastases. Safety and efficacy of tucatinib combined with paclitaxel, pertuzumab, and trastuzumab are unknown and were tested in a planned 10 patient (pt) safety run-in of the I-SPY 2 trial. Methods: Women with tumors ≥ 2.5cm were eligible for screening. Only pts with tumors that were HER2+ by FISH were eligible for this treatment. Treatment included tucatinib (max dose 300 mg) BID for 12 weeks with weekly paclitaxel 80 mg/m2 and trastuzumab (2 mg/kg weekly following loading), and pertuzumab (420 mg every 3 weeks following loading), followed by doxorubicin/cyclophosphamide (AC) every 2 weeks x 4. The control arm was weekly paclitaxel and trastuzumab with pertuzumab for 12 weeks followed by AC every 2 weeks x 4. All pts undergo serial MR imaging and response at 3 & 12 weeks is combined with real time pCR data to estimate, and continuously update, the predicted pCR rate for each trial arm. The goal of the trial is to identify/graduate regimens with ≥85.% Bayesian predictive probability of success (i.e. demonstrating superiority to control) in a future 300-patient phase 3 neoadjuvant trial with a pCR endpoint. This run-in arm was conducted to determine safety of combining tucatinib with paclitaxel/trastuzumab/pertuzumab, monitoring special adverse events of interest including LFT elevations and gastrointestinal toxicities.Methods: The I-SPY 2 methods have been previously published. Results: 20 pts were evaluable in tucatinib treatment arm. The control arm included 329 historical controls enrolled since April 2010. The initial tucatinib dose was 300 mg BID. After enrollment of the first 8 pts, there were 3 pts with grade 3 LFT elevations, 2 pts with grade 2/3 diarrhea, 1 pt with grade 2 neutropenia, and 1 pt with grade 3 nausea. After this safety review, the tucatinib dose was lowered to 250 mg BID. Among 5 additional pts enrolled, 3 developed grade 2/3 LFT abnormalities. The protocol was then modified to tucatinib 150 mg BID days 1-28 and then 250 mg BID days 29-84; 7 pts were treated. Safety data were reviewed after 20 pts were enrolled; the arm was then suspended due to similar LFT elevations regardless of tucatinib dose reduction or schedule. 7 of 20 pts (35%) had reversible Grade 3 or higher ALT/AST elevation (Table). No pt met criteria for Hy’s Law. In terms of efficacy, 12 of 14 evaluable pts had &gt; 80% reduction of tumor volume by 12 weeks, measured by MRI assessment of functional tumor volume (FTV). Conclusion: The goal of the run-in arm was to determine the safety of adding tucatinib to the combination of paclitaxel/trastuzumab/pertuzumab. The addition of tucatinib resulted in unacceptable but reversible LFT elevations despite tucatinib dose reduction. Tucatinib containing therapy resulted in &gt;80% decline in tumor volume at 12 weeks in 86% of pts. Tucatinib showed a high level of activity when combined with paclitaxel/trastuzumab/pertuzumab, but the combination is not feasible. Table: Number of pts with grade 2, 3, and 4 LFT elevations by treatment schedule (highest grade per patient per event, ALT or Treatment scheduleGrade 2 LFT elevationGrade 3 LFT elevationGrade 4 LFT elevationTucatinib 300 mg BID030Tucatinib 250 mg BID210Tucatinib 150 mg BID days 1-28 followed by 250 mg BID days 29 to 84112 Citation Format: David A Potter, Erin Roesch, Christina Yau, Ruixiao Lu, Denise Wolf, Susan Samson, Debra Stafford, Kathy S Albain, Claudine Isaacs, Meghana Trivedi, Douglas Yee, Judy Boughey, Alexandra Thomas, A. Jo Chien, Nola Hylton, Wen Li, Angela DeMichele, Jane Perlmutter, W. Fraser Symmans, Dawn L Hershman, Michelle Melisko, Laura J van 't Veer, Amy Wilson, Smita M Asare, Donald A Berry, Richard Schwab, Hope S Rugo, Laura J Esserman. Evaluation of Tucatinib + (Paclitaxel + Pertuzumab + Trastuzumab) followed by AC in high-risk HER2 positive (HER2+) stage II/III breast cancer: Results from the I-SPY 2 TRIAL [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr PD8-07.

Abstract Background Transcriptomic immune-related gene signatures have been associated with achievement of pathologic complete response (pCR) and prognosis in the neoadjuvant setting. I-SPY 2 is a multicenter, phase 2 platform trial using response-adaptive randomization within subtypes defined by receptor status (HR/HER2) and MammaPrint (MP) risk to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. Given racial disparities in mortality from breast cancer and the paucity of racial demographic data from clinical trials, we aimed to evaluate the association between racial groups and baseline characteristics, including expression-based subtypes and immune signatures, treatment response, and prognosis of patients enrolled in the I-SPY 2 TRIAL. Methods Our study population included 990 I-SPY 2 patients. 15 patients identified as part of a racial group with &lt;10 patients enrolled in the trial and were excluded from analysis. Pre-treatment expression data was available for 971 patients. Follow-up data was available for 907 patients; median follow-up time of 4.4 yrs. Chi-square test was used to assess associations between racial groups and pre-treatment SBR grade, HR/HER2 defined subtypes, intrinsic subtype (defined by BluePrint 80-gene molecular subtyping) and residual cancer burden (RCB) class. Logistic regression was used to evaluate race association with pCR. Cox proportional hazard modeling was used to assess the association between racial groups and event free survival (EFS) in a univariate setting, adjusting for pCR status. Association between racial groups and 28 expression signatures related to immune, proliferation, ER and HER2 pathway was analyzed using ANOVA with post-hoc Tukey test in the overall population and in each receptor subtype. Results Of 975 patients included in our analysis, 787 (81%) were White, 68 (7%) were Asian, and 120 (12%) were Black or African American. No significant associations between race and pre-treatment SBR grade (p=0.49), HR/HER2 defined subtypes (p=0.09), or expression-based subtypes (p=0.25) were observed. pCR rates do not significantly differ by racial groups (Odds ratio of pCR relative to White: 1.00 for Asian and 0.89 for Black or African American); and no significant differences in RCB class distribution by race was observed (p=0.88). Event free survival was not associated with patient racial group in a univariate Cox model (Hazard ratio relative to White: 1.10, p=0.73 for Asian and 1.37, p=0.13 for Black or African American). Among the 28 expression signatures evaluated, four were differentially expressed among racial groups within the overall population (F-test p&lt;0.05): IFN module, B cell signature, Dendritic cell signature, and Mitotic score. Pairwise comparisons between racial groups with post-hoc Tukey test identified significant differences in IFN module expression between Black or African American vs. White (p=0.019) and Dendritic cell signature expression between Asian vs White (p=0.047). Among patients in the TNBC subtype, three signatures (dendritic cell signature, macrophage signature and ERBB2 module) were differentially expressed between Black or African American and White patients (p=0.002, 0.016 and 0.007). Conclusion Our analysis demonstrates that among women with high risk breast cancer, race does not affect subtype specific response rates nor event free survival. Distribution of subtypes previously shown to be associated with pCR in the I-SPY2 trial did not significantly differ among racial groups indicating race is less likely than tumor biology to predict response. The decreased expression of immune signatures observed in Black or African American women with TNBC suggests possible differential sensitivity to immunotherapy plus combination chemotherapy. Tumor immune multiplex studies are underway to further investigate. Citation Format: Beverly Kyalwazi, Christina Yau, Olufunmilayo Olopade, A. Jo Chien, Anne Wallace, Andres Forero-Torres, Lajos Pusztai, Erin Ellis, Kathy Albain, Anne Blaes, Barbara Haley, Judy Boughey, Anthony Elias, Amy Clark, Claudine Isaacs, Rita Nanda, Hyo Han, Rachel Yung, Debu Tripathy, Kristen Edmiston, Rebecca Viscusi, Donald Northfelt, Qamar Khan, Ashish Sanil, Scott Berry, Smita Asare, Amy Wilson, Gillian Hirst, Nola Hylton, Michelle Melisko, Jane Perlmutter, Hope Rugo, Fraser Symmans, Laura van ‘t Veer, Donald Berry, Laura Esserman. Analysis of clinical outcomes and expression-based immune signatures by race in the I-SPY 2 trial [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr GS4-02.