Citations

BackgroundFine needle aspiration (FNA) is commonly used for the preoperative evaluation of salivary gland tumors. Tumor grade is a key factor influencing clinical management of salivary gland carcinomas (SGCs). To assess the ability to grade nonbasaloid SGCs in FNA specimens, an international panel of cytopathologists convened to review and score SGC cases.MethodsThe study cohort included 61 cases of primary SGC from the pathology archives of 3 tertiary medical centers. Cases from 2005 to 2016 were selected, scanned, and digitized. Nineteen cytopathologists blinded to the histologic diagnosis reviewed the digitized cytology slides and graded them as low, high, or indeterminate. The panelists' results were then compared to the tumor grades based on histopathologic examination of the corresponding resection specimens.ResultsAll but 2 of the 19 (89.5%) expert panelists review more than 20 salivary gland FNAs per year; 16 (84.2%) of the panelists work at academic medical centers, and 13 (68.4%) have more than 10 years' experience. Participants had an overall accuracy of 89.4% in the grading of SGC cases, with 90.2% and 88.3% for low‐ and high‐grade SGC, respectively. Acinic cell carcinoma and mucoepidermoid carcinoma had the highest degree of accuracy, while epithelial‐myoepithelial carcinoma and salivary duct carcinoma had the lowest degree of accuracy. As expected, the intermediate‐grade SGC cases showed the greatest variability (high‐grade, 42.1%; low‐grade, 37.5%, indeterminate, 20.4%).ConclusionThis study confirms the high accuracy of cytomorphologic grading of primary SGC by FNA as low‐ or high‐grade. However, caution should be exercised when a grade cannot be confidently assigned.

AbstractSystemic inflammation can lead to coagulopathy and disseminated intravascular coagulation (DIC). In prior studies, the recombinant A2 domain of human von Willebrand factor (VWF; A2 protein) attenuated DIC and decreased mortality in lipopolysaccharide (LPS)-treated mice. Here, we performed studies to dissect the mechanism by which the A2 protein moderates DIC. We used confocal microscopy to analyze the fibrin clot structure in plasma from healthy humans and endotoxemic mice, turbidity assays to examine fibrin polymerization, and a murine model for LPS-induced DIC and introduced a loss-of-function mutation into the A2 protein for fibrin. The mutation of the residue E1567 located in the α2 helix of the folded A2 domain of VWF inhibited binding activity for fibrin, possibly mapping a novel region containing a putative binding site for fibrin. The A2 protein increased the initial rate of change of fibrin polymerization, intercalated into the fibrin network, and modified the resultant clot structure in vitro. Furthermore, ex vivo experiments using plasma from mice with endotoxemia treated with the A2 protein revealed an increased rate of fibrin formation and an altered clot structure as compared with plasma from nontreated sick animals. Moreover, and in contrast to the A2 mutant, the A2 protein improved survival and reduced fibrin deposition and microvascular thrombosis in mice with endotoxemia-induced DIC. Importantly, in vivo and in vitro studies indicated that the A2 protein did not affect experimental thrombosis. Thus, we provide evidence for a novel treatment to attenuate systemic inflammation-induced coagulopathy/DIC via targeting fibrin formation, without an increased risk for bleeding.

Objective This study aimed to develop and validate a patient-reported outcome measure (PROM) in acute pancreatitis (AP) as an endpoint centred on the patient. Design A PROM instrument (PAtieNt-rePoRted OutcoMe scale in acute pancreatItis, an international proSpEctive cohort study, PAN-PROMISE scale) was designed based on the opinion of patients, professionals and an expert panel. The scale was validated in an international multicentre prospective cohort study, describing the severity of AP and quality of life at 15 days after discharge as the main variables for validation. The COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) methodology was applied. Both the design and validation stages considered the content and face validity of this new instrument; the metric properties of the different items, reliability (reproducibility and internal consistence), the construct, structural and criterion validity, responsiveness and interpretability of this scale. Results PAN-PROMISE consists of a seven-item scale based on the symptoms that cause the most discomfort and concern to patients with AP. The validation cohort involved 15 countries, 524 patients. The intensity of symptoms changed from higher values during the first 24 hours to lower values at discharge and 15 days thereafter. Items converged into a unidimensional ordinal scale with good fit indices. Internal consistency and split-half reliability at discharge were adequate. Reproducibility was confirmed using test–retest reliability and comparing the PAN-PROMISE score at discharge and 15 days after discharge. Evidence is also provided for the convergent-discriminant and empirical validity of the scale. Conclusion The PAN-PROMISE scale is a useful tool to be used as an endpoint in clinical trials, and to quantify patient well-being during the hospital admission and follow-up. Trial registration number NCT03650062

Coronavirus disease 2019 (COVID-19) is a global pandemic that is wreaking havoc on the health and economy of much of human civilization. Electrophysiologists have been impacted personally and professionally by this global catastrophe. In this joint article from representatives of the Heart Rhythm Society, the American College of Cardiology, and the American Heart Association, we identify the potential risks of exposure to patients, allied healthcare staff, industry representatives, and hospital administrators. We also describe the impact of COVID-19 on cardiac arrhythmias and methods of triage based on acuity and patient comorbidities. We provide guidance for managing invasive and noninvasive electrophysiology procedures, clinic visits, and cardiac device interrogations. In addition, we discuss resource conservation and the role of telemedicine in remote patient care along with management strategies for affected patients.

Abstract Introduction: Although HER2+ breast cancer (BC) is considered a moderately immunogenic tumor, several studies have shown a role of pre-existing immunity associated with favorable long-term prognosis and better response to treatment. In this study, we performed exploratory analyses to assess whether the efficacy of HER2 targeted treatment in the MARIANNE trial correlated with immune gene expression. Methods: MARIANNE (NCT01120184) is a phase 3 study in patients (pts) with centrally confirmed HER2+ local advanced/metastatic BC naïve to prior treatments in the advanced disease. Pts were randomized (1:1:1) to trastuzumab+taxane (HT), T-DM1, or T-DM1+Petuzumab (P) and the trial showed noninferior PFS of T-DM1 and T-DM1+P vs HT. Gene expression (RNA) analysis was performed on tumor samples by a custom 800-gene codeset on the nCounter platform. PD-L1, CD8 expressions and immune gene signatures (sign) analyses were assessed by multivariate Cox regression models using median (cut-off) as categorical variable and adjusted by prior HT, presence of visceral disease, world region, baseline ECOG, measureable disease at baseline, therapy setting, HER2 mRNA expression, PIK3CA mutation status. Results: MARIANNE randomized 1095 pts (HT, n=365; T-DM1, n=367; T-DM1+P, n=363). Gene expression results were available for 671 pts (61.3% of the intent-to-treat [ITT] population) which was representative of ITT. In ITT, HR below 1 was observed when comparing pts with high (>median) vs low (≤median) immune gene expression by clinical outcome suggesting a potential association of high immune marker expression with improved PFS (Table 1) and to some extent with OS (data not shown). This association was primarily observed in the T-DM1 arm where the HR suggested a risk reduction of disease progression(PD)/death especially in the high Teff, high PD-L1 and high CD8 subgroups, and to some extent in the HT arm (Table 1). When assessing the predictive impact on PFS by comparing T-DM1 vs HT, HR below 1 was observed especially in pts with high Teff signature, high PD-L1 and high CD8 expressions (HR 0.67 (95% CI (0.47-0.95)), HR 0.68 (95% CI (0.48-0.97), and HR 0.64 (95%CI 0.44-0.93), respectively). When comparing T-DM1+P vs. HT, HR below 1 was observed especially in pts with low Teff signature and low PD-L1 expression (HR 0.70 (95% CI (0.50-0.99), and HR 0.68 (95% CI (0.48-0.96) respectively). No clear differences between immune gene expression subgroups was observed when comparing treatment arms in regards to OS (data not shown). Conclusions: In the exploratory analysis from the MARIANNE study, high immune gene expression, especially in the high PD-L1, CD8 and Teff subgroups, showed an association with improved clinical benefit with HRs reflecting for a risk reduction of PD/death for PFS and partially for OS. This association was less obvious in the T-DM1+P arm. When comparing the treatments effect, the data showed a potential impact of high Teff signature, and high CD8 and PD-L1 expressions on T-DM1 and less on HT. The potential opposite association of low Teff signature and low PD-L1 expression with improved benefit in the T-DM1+P arm was unexpected and needs further investigation. Table 1: Prognostic biomarker effect on PFSBiomarker by categories (>Median vs ≤Median)HR (95% CI) ITT n=671HR (95% CI) HT n=220HR (95% CI) T-DM1 n=227HR (95% CI) T-DM1+P n=224Teff sign0.89 (0.73-1.09)0.97 (0.68-1.38)0.64 (0.45-0.91)1.09 (0.75-1.58)Th1 cytokine sign0.91 (0.74-1.11)0.92 (0.64-1.31)0.78 (0.55-1.11)0.96 (0.67-1.36)Checkpoint inhibitor sign0.95 (0.78-1.15)0.91 (0.64-1.29)0.90 (0.64-1.26)1.02 (0.71-1.47)PD-L10.80 (0.66-0.98)0.79 (0.55-1.13)0.62 (0.44-0.87)1.07 (0.74-1.55)CD80.91 (0.75-1.11)1.10 (0.77-1.57)0.66 (0.46-0.93)0.98 (0.68-1.41) Citation Format: Edith A Perez, Sanne Lysbet de Haas, Carlos H Barrios, Wolfgang Eiermann, Masakazu Toi, Young-Hyuck Im, Pier Franco Conte, Miguel Martin, Tadeusz Pienkowski, Xavier B Pivot, Howard A Burris III, Chiara Lambertini, Silke Hoersch, Monika Patre, Paul Anthony Ellis. Association of immune gene expression with outcome in the MARIANNE phase 3 clinical trial in HER2-positive metastatic breast cancer (MBC) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD5-11.

Abstract Background: Combination treatments of CDK4 & 6 inhibitors (CDK4 & 6i) with endocrine therapy (ET) have improved outcomes in patients with HR-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). Aside from estrogen receptor positivity (ER+), predictive biomarkers of clinical benefit from CDK4 & 6i in combination with ET remain elusive. We assessed clinical outcomes by genomic alterations detected in baseline circulating tumor DNA (ctDNA) from patients treated with abemaciclib plus a nonsteroidal aromatase inhibitor (NSAI) versus placebo plus NSAI in the Phase 3 study MONARCH 3 (NCT02246621). Methods: MONARCH 3 randomized 493 postmenopausal women with HR+, HER2- ABC who had no prior systemic therapy in the advanced setting to treatment with abemaciclib plus NSAI or placebo plus NSAI. Biomarker analysis of baseline ctDNA was an exploratory objective; plasma was analyzed by the Guardant360 next-generation sequencing (NGS)-based assay to identify potential tumor-related (i.e., somatic) genomic alterations including point mutations (SNV), indels, amplifications, and fusions in over 70 cancer-related genes. Genomic alterations detected in baseline ctDNA were associated with clinical outcomes including progression-free survival (PFS) and objective response rate (ORR). Results: Baseline ctDNA results were available for 295 patients (201 abemaciclib; 94 placebo) with 83% of patients harboring one or more detectable genomic alterations. Commonly altered genes of interest (% frequency) detected in baseline ctDNA included: PIK3CA (38%); TP53 (26%); EGFR (15%); FGFR1 (12%); NF1 (12%); MYC (9%); CCND1 (9%); ESR1 (5%).Overall, patients treated with placebo plus NSAI who harbored detectable ctDNA genomic alterations had shorter median PFS compared to patients without detectable genomic alterations, as shown in the Table (14.9 months [95% CI: 11.0-23.1] vs 19.2 months [95% CI 9.4-NR]). Moreover, genomic alterations in EGFR, FGFR1, MYC, and CCND1 were associated with median PFS <12 months with placebo plus NSAI. However, consistent with the intent-to-treat population, the addition of abemaciclib to NSAI benefitted these genomic subgroups, regardless of ctDNA gene alterations. Additional genomic results, including alterations in cell cycle-associated genes, will be presented. Conclusions: In this exploratory subgroup analysis, the presence of detectable ctDNA genomic alterations was associated with shorter PFS with placebo plus NSAI. Consistently, abemaciclib added to NSAI improved outcomes for genomically identified subgroups. In contrast to prior studies, there was no subgroup (e.g., patients harboring FGFR1 alterations) that did not derive benefit from abemaciclib, supporting the efficacy of abemaciclib, including in difficult to treat tumors. These findings are hypothesis-generating and warrant further investigations in clinical studies of CDK4 & 6i in combination with ET. TableAbemaciclib + NSAIPlacebo + NSAIEvents, n/NMedian PFS (95% CI)Events, n/NMedian PFS (95% CI)Hazard Ratio (95% CI)OVERALLITT population170 / 32828.2 (23.7 - 33.9)123 / 16514.8 (11.2 - 19.2)0.52 (0.42 - 0.66)TR population93 / 20138.7 (31.1 - NR)71 / 9416.5 (11.7 - 23.1)0.45 (0.33 - 0.61)Any Gene AlterationDetected83 / 16634.1 (27.2 - 40.0)62 / 7914.9 (11.0 - 23.1)0.47 (0.34 - 0.66)Not detected10 / 35NR (36.4 - NR)9 / 1519.2 (9.40 - NR)0.31 (0.13 - 0.78)TP53Detected29 / 5327.0 (14.1 - NR)19 / 2315.4 (5.7 - 30.4)0.53 (0.30 - 0.95)Not detected64 / 14839.9 (34.1 - NR)52 / 7117.5 (11.7 - 24.2)0.42 (0.29 - 0.60)EGFRDetected10 / 26NR (32.4 - NR)16 / 1710.9 (2.1 - 24.7)0.20 (0.09 - 0.47)Not detected83 / 17536.4 (27.7 - NR)55 / 7717.6 (14.6 - 25.5)0.52 (0.37 - 0.73)FGFR1Detected15 / 2532.8 (10.1 - NR)10 / 117.6 (1.9 - 15.4)0.37 (0.16 - 0.85)Not detected78 / 17639.9 (31.1 - NR)61 / 8319.2 (14.6 - 26.5)0.45 (0.32 - 0.63)NF1Detected10 / 2435.9 (27 - NR)8 / 1014.6 (1.6 - 33.4)0.33 (0.13 - 0.84)Not detected83 / 17738.7 (30.8 - NR)63 / 8417.5 (11.7 - 24.2)0.47 (0.33 - 0.65)MYCDetected11 / 1720.1 (5.5 - NR)9 / 106.5 (1.2 - 15.7)0.33 (0.13 - 0.86)Not detected82 / 18438.9 (32.9 - NR)62 / 8419.2 (14.6 - 26.5)0.45 (0.32 - 0.63)CCND1Detected8 / 1632.8 (5.5 - NR)10 / 107.2 (3.6 - 9.0)0.28 (0.10 - 0.77)Not detected85 / 18538.7 (31.1 - NR)61 / 8417.6 (14.6 - 25.5)0.48 (0.34 - 0.67)n = number of patients with events; N = total number of patients in the corresponding population and treatment arm; NR = not reached. TR population consists of patients in the ITT population from whom a valid baseline ctDNA result has been obtained. Citation Format: Matthew P Goetz, J. Thaddeus Beck, Mario Campone, Sara Hurvitz, Seock-Ah Im, Stephen Johnston, Antonio Llombart-Cussac, Miguel Martin, Joohyuk Sohn, Masakazu Toi, Lacey M Litchfield, Hillary T Graham, Hong Wang, Sameera R Wijayawardana, Valerie M Jansen, Angelo Di Leo. Efficacy of abemaciclib based on genomic alterations detected in baseline circulating tumor DNA from the MONARCH 3 study of abemaciclib plus nonsteroidal aromatase inhibitor [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD2-06.

Abstract Background: Abemaciclib plus nonsteroidal aromatase inhibitors (AI) demonstrated efficacy with a tolerable safety profile as initial treatment for postmenopausal women with HR+, HER2− advanced breast cancer in the MONARCH 3 trial. In the intent-to-treat (ITT) population, the updated progression-free survival (PFS) with 12 months of additional follow-up was 28.2 versus 14.8 months (HR [95% CI]: 0.525 [0.415, 0.665]; p<.0001) in the abemaciclib plus AI versus placebo plus AI arms, respectively. Here we report data from the additional 12 months of follow-up on tumor response for the ITT population and exploratory subgroups previously identified as significantly prognostic (Di Leo et al. 2018). Methods: In MONARCH 3, a randomized, double-blind, phase III trial, 493 postmenopausal women with HR+, HER2− advanced breast cancer and no prior systemic therapy in the advanced setting, received an AI (anastrozole or letrozole) plus abemaciclib or placebo. From the October 31, 2018 cutoff, secondary endpoints including objective response rate ([ORR], complete response [CR] + partial response [PR]), time to response (TTR), and duration of response ([DoR], time from a confirmed CR or PR until disease progression or death) were assessed in the ITT population and exploratory subgroups previously reported as significantly prognostic. Waterfall plots will be used to illustrate the magnitude of change in tumor size for each subgroup (to be presented). Results: In patients with measurable disease, the ORR was 62.5% (95% CI: 56.7, 68.2) in the abemaciclib plus AI arm and 44.7% (95% CI: 36.2, 53.2) in the placebo plus AI arm (p≤.001). Additional follow-up confirmed that all prognostic subgroups received benefit from the addition of abemaciclib to AI, consistent with the ITT population, as evidenced by change in ORR, with the largest effects observed in subgroups of patients with liver metastases, progesterone receptor-negative tumors, high grade tumors, or treatment-free interval of <36 months (Table). Median TTR was similar between the two treatment arms (abemaciclib plus AI: 3.62 months; placebo plus AI: 3.65 months), and this was generally consistent across subgroups. Responses were more durable in the abemaciclib plus AI arm (median DoR: 32.71 months; 95% CI: 25.74, -) versus the placebo plus AI arm (median DoR: 17.49 months; 95% CI: 11.61, 22.19), including in poor prognostic subgroups. Conclusions: Extended follow-up in the MONARCH 3 trial further confirmed that the addition of abemaciclib to AI is associated with durable tumor responses, including those in patients with clinically poor prognostic characteristics. References: Di Leo A et al. NPJ Breast Cancer. 2018;4:41. Clinical trial information: NCT02246621 This study was funded by Eli Lilly and Company Table: Objective Response RateAbemaciclib + AIPlacebo + AIORR ChangeNn (%)Nn (%)%Measurable disease population269168 (62.5)13259 (44.7)17.8Liver metastasesYes4727 (57.45)306 (20.00)37.45No222141 (63.51)10253 (51.96)11.55Progesterone receptor statusNegative6137 (60.66)298 (27.59)33.07Positive206130 (63.11)10351 (49.51)13.60Treatment-free interval<36 months3117 (54.84)225 (22.73)32.11≥36 months7442 (56.76)3216 (50.00)6.76Tumor gradeHigh5739 (68.42)2811 (39.29)29.13Intermediate/ Low13992 (66.19)7535 (46.67)19.52ECOG PS111275 (66.96)5022 (44.00)22.96015793 (59.24)8237 (45.12)14.12Bone-only diseaseNo256162 (63.28)12253 (43.44)19.84YesNA*NA*NA*NA*NA*N= total number of patients in each subgroup; n= number of responder patients; NA=not applicable*Response rate not reported for bone-only disease because majority of lesions were not measurable Citation Format: Joyce O’Shaughnessy, Stephen Johnston, Miguel Martin, Jens Huober, Masakazu Toi, Valerie AnneMarie Andre, Holly Rene Martin, Molly Catherine Hardebeck, Angelo Di Leo, Matthew Philip Goetz. Updated subgroup tumor response of abemaciclib plus aromatase inhibitor for hormone receptor positive (HR+), HER2 negative advanced breast cancer (MONARCH 3) [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P1-19-09.

Abstract Background: Recent studies have demonstrated independent validation of the prognostic relevance of residual cancer burden (RCB) after neoadjuvant chemotherapy. However, a pooled subject-level analysis of multiple cohorts is needed to determine estimates of long-term prognosis for each class of RCB in each phenotypic subtype of breast cancer (BC) to better inform on patient outcomes. Also, a pooled subject-level analysis allows more detailed analyses of generalizability of the prognostic meaning of RCB assessments in a broader experience of practice settings. Method: Subject-level RCB results, with relevant clinical and pathologic stage, tumor subtype and grade, demographic, treatment and follow-up data from 11 institutes/trials are being collected for combined analysis. The association between the continuous RCB index and event-free survival (EFS), and distant recurrence free survival (DRFS) were assessed using mixed effect Cox models with the incorporation of random RCB coefficients to account for between-study heterogeneity. We will also allow for differences in baseline hazard across biological BC subtypes and, if needed, across studies as well. In addition to this stratified mixed effect model, a multivariate analysis adjusting for age, T-category, nodal status and grade was performed within each subtype. In addition, mixed effect Cox models will be employed to evaluate association between RCB index with EFS and DRFS within each HR/HER2 subtype. Kaplan Meier estimates of EFS and DRFS at 5 and 10 years were computed for each RCB class within subtype. Results: We analyzed subject-level data from 9 institutes/trials representing 4077 patients currently available from an anticipated final total of 4,800 patients (to be presented at the meeting). There were 950 EFS and 876 DRFS events during follow up (median 65 months, IQR: 70 months). RCB index (continuous) was independently prognostic within each subtype: HR+/HER2- (EFS HR (per unit increase in RCB index) =1.64, 95%CI 1.48-1.82; DRFS HR=1.68, 1.51-1.87), HR+/HER2+ (EFS HR=1.80, 1.57-2.05; DRFS HR=1.93, 1.67-2.24), HR-/HER2+ (EFS HR=2.15, 1.76-2.62; DRFS HR=2.10, 1.77-2.50), and HR-/HER2- (EFS HR=2.05, 1.89-2.22; DRFS HR=2.16, 1.90-2.46); and remained prognostic in multivariate models adjusting for age, grade, and clinical T and N stage at diagnosis. Table 1 contains the response rate and estimated EFS at 5 years and 10 years for each RCB class within each HR/HER2 phenotype (DRFS results were similar). Conclusions: Long-term prognosis after pCR was similarly excellent in all phenotypic subtypes. RCB index and classification was independently and strongly prognostic in all subtypes, and generalizable to multiple practice settings. Prognostic differences by RCB class occurred within 5 years in HR- BC, but extended to 10 years in HR+ BC. RCB-I had slightly worse EFS than pCR in HR- BC and HR+/HER2+ BC (after 5 years), but the same EFS as pCR in HR+/HER2- BC. Complete analysis of all subjects, including neoadjuvant treatments, will be presented at the meeting. PhenotypeOutcomepCRRCB-IRCB-IIRCB-IIIHR+/HER2-Frequency (%)11%10%52%27%(N=1467)5 yr EFS (95% CI)91% (86-96)93% (89-98)82% (79-85)70% (65-75)10 yr EFS (95% CI)84% (75-93)88% (82-95)71% (67-75)52% (46-58)HR+/HER2+Frequency (%)38%18%35%9%(N=762)5 yr EFS (95% CI)94% (91-97)93% (88-98)78% (73-84)49% (37-65)10 yr EFS (95% CI)91% (86-96)79% (70-90)65% (59-73)42% (29-60)HR-/HER2+Frequency (%)66%11%18%5%(N=550)5 yr EFS (95% CI)93% (90-96)88% (79-97)60% (50-71)45% (30-69)10 yr EFS (95% CI)90% (86-94)84% (74-95)56% (46-68)45% (30-69)HR-/HER2-Frequency (%)41%13%33%13%(N=1293)5 yr EFS (95% CI)92% (90-94)85% (79-91)68% (63-72)28% (21-36)10 yr EFS (95% CI)87% (82-91)80% (72-88)63% (58-68)24% (18-33) Citation Format: Christina Yau, Marieke van der Noordaa, Jane Wei, Marie Osdoit, Fabien Reyal, Anne-Sophie Hamy, Marick Lae, Miguel Martin, Maria del Monte, I-SPY 2 TRIAL Consortium, Judy C Boughey, Rebekah Gould, Jelle Wesseling, Tessa Steenbruggen, Maartje van Seijen, Gabe Sonke, Stephen Edge, Stephen-John Sammut, Elena Provenzano, Jean Abraham, Peter Hall, Ashley Graham, Lorna Mackintosh, David Cameron, Alice Wang, Priyanka Sharma, Kimberly Cole, Lajos Pusztai, Mi-Ok Kim, Laura van ‘t Veer, Laura Esserman, W. Fraser Symmans. Residual cancer burden after neoadjuvant therapy and long-term survival outcomes in breast cancer: A multi-center pooled analysis [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr GS5-01.

Recent clinical trials have addressed the notion of early treatment of smoldering multiple myeloma (SMM). The results evidence improvement in progression-free survival and, in one study, overall survival. Although the treatment of SMM can be considered under specific circumstances, we propose here that careful interpretation of the clinical trials and the patient-specific data are needed before recommending therapy. In particular, many questions remain regarding the best regimen to be used as well as how to adapt based on the underlying disease biology. Hematologists should have a very thorough understanding of models designed to predict the progression from SMM to multiple myeloma, because their correct interpretation is paramount to establish proper care. Although there is no doubt that treatment should be started before overt end-organ damage, we do not believe that the current data support the widespread treatment of all SMM.

10503 Background: Gender bias can be reinforced through the use of gender-subordinating language and differences in the forms of address. We examined how professional titles were used during speakers’ introductions at the American Society of Clinical Oncology (ASCO) Annual Meeting. Methods: A retrospective observational study of video-archived speaker introductions at the 2017 and 2018 ASCO annual meetings was conducted. Data were extracted by mixed-gender coders. Professional address was defined as professional title followed by full name or last name. Multivariable logistic regressions were used to identify factors associated with the form of address. Results: 2511 videos were reviewed and 812 met inclusion criteria. Regarding speakers’ characteristics, 530 (65%) were non-Hispanic white (NHW), 743 (92%) held a MD or MD-PhD degree, and 484 (60%) were an associate or full professor. Female speakers were less likely to receive a professional address compared to male speakers (61% vs. 81%, p < 0.001). Female speakers were more likely to be introduced by first name only (17% vs. 3%, p < 0.001). Males were less likely to use a professional address when introducing female speakers compared to male speakers (53% vs. 80%, p < 0.01). No gender differences in professional address were observed for female introducers (p = 0.13). Male introducers were more likely to address female speakers by first name only compared to female introducers (24% vs. 7%, p < 0.01). In a multivariable regression including gender, race, degree, and academic rank, male speakers were more likely to receive a professional address compared to female speakers (OR: 2.67, 95%CI: 1.81-3.94, p < 0.01). Black speakers of both genders were less likely to receive a professional address compared to NHW (OR: 0.10, 95%CI: 0.01-0.53, p < 0.01). Female gender was a predictor for a non-professional form of address (first name only) (OR: 9.50, 95%CI: 4.38-20.62, p < 0.01). Conclusions: When introduced by men, female speakers were less likely to receive a professional address and more likely to be introduced by first name only compared to male speakers. Selective use of forms of address may strengthen gender bias; more research is needed to explore the causes of this disparity and its influence.