Monitoring response to neoadjuvant chemotherapy in triple negative breast cancer using circulating tumor DNA.

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype with poor prognosis. We aimed to determine whether circulating tumor DNA (ctDNA) and circulating tumor cell (CTC) could predict response and long-term outcomes to neoadjuvant chemotherapy (NAC). METHODS: Patients with TNBC were enrolled between 2017-2021 at The University of Texas MD Anderson Cancer Center (Houston, TX). Serial plasma samples were collected at four timepoints: pre-NAC (baseline), 12-weeks after NAC (mid-NAC), after NAC/prior to surgery (post-NAC), and one-year after surgery. ctDNA was quantified using a tumor-informed ctDNA assay (SignateraTM, Natera, Inc.) and CTC enumeration using CellSearch. Wilcoxon and Fisher's exact tests were used for comparisons between groups and Kaplan-Meier analysis used for survival outcomes. RESULTS: In total, 37 patients were enrolled. The mean age was 50 and majority of patients had invasive ductal carcinoma (34, 91.9%) with clinical T2, (25, 67.6%) node-negative disease (21, 56.8%). Baseline ctDNA was detected in 90% (27/30) of patients, of whom 70.4% (19/27) achieved ctDNA clearance by mid-NAC. ctDNA clearance at mid-NAC was significantly associated with pathologic complete response (p = 0.02), whereas CTC clearance was not (p = 0.52). There were no differences in overall survival (OS) and recurrence-free survival (RFS) with positive baseline ctDNA and CTC. However, positive ctDNA at mid-NAC was significantly associated with worse OS and RFS (p = 0.0002 and p = 0.0034, respectively). CONCLUSIONS: Early clearance of ctDNA served as a predictive and prognostic marker in TNBC. Personalized ctDNA monitoring during NAC may help predict response and guide treatment.

Going Above and Beyond With SJTs: Impact of Applicant Characteristics on Open Response SJT Participation.

BACKGROUND: Situational judgment tests (SJT) have gained popularity as a standardized assessment of nontechnical competencies for applicants to medical school and residency. SJT formats range from rating the effectiveness of potential response options to solely open response. We investigated differences in test-taking patterns between responders and nonresponders to optional open response SJT questions during the application process. METHODS: This was a prospective multi-institutional study of general surgery applicants to seven residency programs. Applicants completed a 32-item SJT designed to measure ten core competencies: adaptability, attention to detail, communication, dependability, feedback receptivity, integrity, professionalism, resilience, self-directed learning, and team orientation. Each SJT item included an optional, nonscored, open response space for applicants to provide a behavioral response if they desired. Trends in applicant gender, race, ethnicity, medical school ranking, and USMLE scores were examined between the responder versus nonresponder group. RESULTS: In total, 1491 general surgery applicants were invited to complete the surgery-specific SJT. Of these, 1454 (97.5%) candidates completed the assessment and 1177 (78.9%) provided additional responses to at least one of the 32 SJT scenario sets. There were no differences in overall SJT performance, USMLE scores (Step 1: 235, SD 14, Step 2: 250, SD 11), race and/or ethnicity between the responder and nonresponder groups. Responders were more likely to be from a top 25 medical school (p < 0.05) compared to the nonresponder group. Among applicants who completed any open response questions, women completed a significantly higher number of questions compared to men (7.21 vs 6.07, p = 0.003). The number of open responses provided correlated with higher scores on SJT items measuring dependability (r = 0.07, p = 0.007). CONCLUSIONS: SJT design and format has the potential to impact test-taker response patterns. SJT developers and adopters should ensure test format and design have no unintended consequences prior to implementation.

Maximizing Standardization While Ensuring Equity: Exploring the Role of Applicant Experiences, Attributes, and Metrics on Performance of a Surgery-Specific Situational Judgment Test.

BACKGROUND: Situational judgment tests (SJT) are hypothetical but realistic scenario-based assessments that allow residency programs to measure judgment and decision-making among future trainees. A surgery-specific SJT was created to identify highly valued competencies among residency applicants. We aim to demonstrate a stepwise process for validation of this assessment for applicant screening through exploration of two often-overlooked sources of validity evidence - relations with other variables and consequences. METHODS: This was a prospective multi-institutional study involving 7 general surgery residency programs. All applicants completed the SurgSJT, a 32-item test aimed to measure 10 core competencies: adaptability, attention to detail, communication, dependability, feedback receptivity, integrity, professionalism, resilience, self-directed learning, and team orientation. Performance on the SJT was compared to application data, including race, ethnicity, gender, medical school, and USMLE scores. Medical school rankings were determined based on the 2022 U.S. News & World Report rankings. RESULTS: In total, 1491 applicants across seven residency programs were invited to complete the SJT. Of these, 1454 (97.5%) candidates completed the assessment. Applicants were predominantly White (57.5%), Asian (21.6%), Hispanic (9.7%), Black (7.3%), and 52% female. A total of 208 medical schools were represented, majority were allopathic (87.1%) and located in United States (98.7%). Less than a quarter of applicants (22.8%; N=337) were from a top 25 school based on U.S. News & World Report rankings for primary care, surgery, or research. Average USMLE Step 1 score was 235 (SD 37) and Step 2 score was 250 (SD 29). Sex, race, ethnicity, and medical school ranking did not significantly impact performance on the SJT. There was no relationship between SJT score and USMLE scores and medical school rankings. CONCLUSIONS: We demonstrate the process of validity testing and importance of two specific sources of evidence-consequences and relations with other variables, in implementing future educational assessments.

Human Ductal Carcinoma In Situ: Advances and Future Perspectives.

Due to widespread adoption of screening mammography, there has been a significant increase in new diagnoses of ductal carcinoma in situ (DCIS). However, DCIS outcomes remain unclear. A large fraction of human DCIS (>50%) may not need the multimodality treatment options currently offered to all DCIS patients. More importantly, while we may be overtreating many, we cannot identify those most at risk of invasion or metastasis following a DCIS diagnosis. This review summarizes the studies that have furthered our understanding of DCIS pathology and mechanisms of invasive progression by using advanced technologies including spatial genomics, transcriptomics, and multiplex proteomics. This review also highlights a need for rethinking DCIS with a more focused view on epithelial states and programs and their cross talk with the microenvironment.

Concomitant Use of Biopsy Clips and Wire Localization in Invasive Breast Cancer is Associated With Successful Clip Retrieval.

INTRODUCTION: Surgical management of the axilla in patients with clinically node-positive breast cancer has shifted to less invasive surgical approaches, such as sentinel lymph node dissection (SLND) and targeted axillary dissection (TAD). Successful retrieval of the biopsy clip marking the lymph node of interest is crucial for assessment of pathologic response and locoregional disease control. METHODS: We performed a retrospective review of patients ≥18 years old with invasive breast cancer and biopsy-proven axillary LN involvement, who underwent LN clip placement from January 2012 to July 2017 at Johns Hopkins Hospital. RESULTS: Of the 128 eligible patients, the median age at diagnosis was 51.5 years (range, 23-92 years) with predominately stage T2-3 disease (54.7% T2, 42.2% T3), of ductal histology (76.6%), and located in the upper outer quadrant (42.2%). Among the 63.3% (81) of patients who received neoadjuvant systemic therapy, 43.2% (35) had a partial response and 30.9% (25) had a complete response. Axillary procedures performed consisted of 36.7% (47) SLND/TAD, 53.9% (69) ALND, and 9.4% (12) SLND/TAD with conversion to ALND. The clipped LN was successfully retrieved in 63.8% (30) of SLND/TADs, 39.1% (27) of ALNDs, and 58.3% (7) of SLND/TADs followed by ALND. Pre-operative node localization by wire and/or skin markings was performed for 16.4% (21) of patients. Among these, 90.5% (19) of clipped LNs were successfully retrieved, compared to 42.1% (45) retrieved in axillary procedures without preoperative node localization. CONCLUSION: Use of preoperative targeted node localization improved rate of clipped LN retrieval across all three types of axillary procedures.

In-vivo Performance of Seven Commercially Available Demineralized Bone Matrix Fiber and Putty Products in a Rat Posterolateral Fusion Model.

Introduction: Demineralized bone matrix (DBM) is a widely used bone graft in spinal fusion. Most commercial DBMs are composed of demineralized bone particles (~125-800 microns) suspended in a carrier that provides improved handling but dilutes the osteoinductive component. DBM fibers (DBF) provide improved osteoconductivity and do not require a carrier. It has been suggested that 100% DBF may offer improved performance over particulate-based DBMs with carrier. Study Design: Seven commercially available DBM products were tested in an athymic rat posterolateral fusion model. There were four 100% DBFs, two DBFs containing a carrier, and one particulate-based DBM containing carrier. Objective: The study objectives were to evaluate the in vivo performance: (1) compare fusion rate and fusion maturity of six commercially available DBFs and one particulate-based DBM, and (2) assess the effect of carrier on fusion outcomes for DBFs in a posterolateral fusion model. Methods: The DBF/DBM products evaluated were: StrandTM Family, Propel® DBM Fibers, Vesuvius® Demineralized Fibers, Optium® DBM Putty, Grafton® DBF, Grafton Flex, and DBX® Putty. Single-level posterolateral fusion was performed in 69 athymic rats. Fusion was assessed bilaterally after 4 weeks by manual palpation, radiograph and CT for bridging bone. Fusion mass maturity was assessed with a CT maturity grading scale and by histology. Statistical analysis was performed using Fishers Exact Test for categorical data and Kruskal-Wallis Test for non-parametric data. Results: Strand Family achieved 100% fusion (18/18) by manual palpation, radiographic and CT evaluation, significantly higher than Propel Fibers, Vesuvius Fibers, Optium Putty, and DBX Putty, and not statistically higher than Grafton DBF and Grafton Flex. Strand Family provided the highest fusion maturity, with CT maturity grade of 2.3/3.0 and 89% mature fusion rate. Fusion results suggest a detrimental effect of carrier on fusion performance. Conclusions: There were large variations in fusion performance for seven commercially available DBM products in an established preclinical fusion model. There were even significant differences between different 100% DBF products, suggesting that composition alone does not guarantee in vivo performance. In the absence of definitive clinical evidence, surgeons should carefully consider available data in valid animal models when selecting demineralized allograft options.