Comprehensive genomic profiling of ESR1, PIK3CA, AKT1, and PTEN in HR(+)HER2(-) metastatic breast cancer: prevalence along treatment course and predictive value for endocrine therapy resistance in real-world practice.

BACKGROUND: The treatment landscape for HR(+)HER2(-) metastatic breast cancer (MBC) is evolving for patients with ESR1 mutations (mut) and PI3K/AKT pathway genomic alterations (GA). We sought to inform clinical utility for comprehensive genomic profiling (CGP) using tissue (TBx) and liquid biopsies (LBx) in HR(+)HER2(-) MBC. METHODS: Records from a de-identified breast cancer clinicogenomic database for patients who underwent TBx/LBx testing at Foundation Medicine during routine clinical care at ~ 280 US cancer clinics between 01/2011 and 09/2023 were assessed. GA prevalence [ESR1mut, PIK3CAmut, AKT1mut, PTENmut, and PTEN homozygous copy loss (PTENloss)] were calculated in TBx and LBx [stratified by ctDNA tumor fraction (TF)] during the first three lines of therapy. Real-world progression-free survival (rwPFS) and overall survival (rwOS) were compared between groups by Cox models adjusted for prognostic factors. RESULTS: ~ 60% of cases harbored 1 + GA in 1st-line TBx (1266/2154) or LBx TF ≥ 1% (80/126) and 26.5% (43/162) in LBx TF < 1%. ESR1mut was found in 8.1% TBx, 17.5% LBx TF ≥ 1%, and 4.9% LBx TF < 1% in 1st line, increasing to 59% in 3rd line (LBx TF ≥ 1%). PTENloss was detected at higher rates in TBx (4.3%) than LBx (1% in TF ≥ 1%). Patients receiving 1st-line aromatase inhibitor + CDK4/6 inhibitor (n = 573) with ESR1mut had less favorable rwPFS and rwOS versus ESR1 wild-type; no differences were observed for fulvestrant + CDK4/6 inhibitor (n = 348). CONCLUSION: Our study suggests obtaining TBx for CGP at time of de novo/recurrent diagnosis, followed by LBx for detecting acquired GA in 2nd + lines. Reflex TBx should be considered when ctDNA TF < 1%.

Methylthioadenosine Phosphorylase Genomic Loss in Advanced Gastrointestinal Cancers.

BACKGROUND: One of the most common sporadic homozygous deletions in cancers is 9p21 loss, which includes the genes methylthioadenosine phosphorylase (MTAP), CDKN2A, and CDKN2B, and has been correlated with worsened outcomes and immunotherapy resistance. MTAP-loss is a developing drug target through synthetic lethality with MAT2A and PMRT5 inhibitors. The purpose of this study is to investigate the prevalence and genomic landscape of MTAP-loss in advanced gastrointestinal (GI) tumors and investigate its role as a prognostic biomarker. MATERIALS AND METHODS: We performed next-generation sequencing and comparative genomic and clinical analysis on an extensive cohort of 64 860 tumors comprising 5 GI cancers. We compared the clinical outcomes of patients with GI cancer harboring MTAP-loss and MTAP-intact tumors in a retrospective study. RESULTS: The prevalence of MTAP-loss in GI cancers is 8.30%. MTAP-loss was most prevalent in pancreatic ductal adenocarcinoma (PDAC) at 21.7% and least in colorectal carcinoma (CRC) at 1.1%. MTAP-loss tumors were more prevalent in East Asian patients with PDAC (4.4% vs 3.2%, P = .005) or intrahepatic cholangiocarcinoma (IHCC; 6.4% vs 4.3%, P = .036). Significant differences in the prevalence of potentially targetable genomic alterations (ATM, BRAF, BRCA2, ERBB2, IDH1, PIK3CA, and PTEN) were observed in MTAP-loss tumors and varied according to tumor type. MTAP-loss PDAC, IHCC, and CRC had a lower prevalence of microsatellite instability or elevated tumor mutational burden. Positive PD-L1 tumor cell expression was less frequent among MTAP-loss versus MTAP-intact IHCC tumors (23.2% vs 31.2%, P = .017). CONCLUSION: In GI cancers, MTAP-loss occurs as part of 9p21 loss and has an overall prevalence of 8%. MTAP-loss occurs in 22% of PDAC, 15% of IHCC, 8.7% of gastroesophageal adenocarcinoma, 2.4% of hepatocellular carcinoma, and 1.1% of CRC and is not mutually exclusive with other targetable mutations.

Prevalence of targetable genomic alterations in young women with advanced breast cancer: a cross-sectional study.

PURPOSE: Approximately 5% of breast cancers each year are diagnosed in young women < 40 years who tend to have worse clinical outcomes. We compared genomic alterations using comprehensive genomic profiling (CGP) of tumor tissue among very young women (< 30 years) and young women (30-39 years) compared to women ≥ 40 years at diagnosis. METHODS: 2049 advanced breast cancer cases were submitted to Foundation Medicine within a 22-month window for CGP. Hybrid-capture based CGP was performed to evaluate all classes of genomic alterations. Tumor mutational burden was determined on at least 0.8 Mbp of sequenced DNA and microsatellite instability was determined on at least 95 loci. Immunocyte PD-L1 expression was determined by immunohistochemistry. RESULTS: Of the total cases, 28 (1.37%) were < 30 years, 159 (7.76%) were 30-39 years, and 1862 (90.87%) were ≥ 40 at time of diagnosis. Breast tumors were less likely to be estrogen receptor positive in younger women (54% of < 30 years, p > 0.05; 60% of 30-39 years, p < 0.001; 69.4% of ≥ 40 years) and more likely to be triple negative (43%, p = 0.05; 33%, p = 0.05; 26.1% respectively). Young women had higher rates of BRCA1 mutations (17.9% <30 years, p < 0.001; 10.1% 30-39 years, p < 0.001; 2.6% ≥40 years), but lower rates of CDH1 (7.1% <30 years, p > 0.05; 5.0% 30-39 years, p < 0.001; 15.4% ≥40 years) and PIK3CA mutations (17.9% <30 years, p = 0.02; 17.6% 30-39 years, p < 0.001; 40.0% ≥40 years). CONCLUSION: Our findings contribute to the growing literature demonstrating unique genetic profiles among young women diagnosed with breast cancer, compared to older women.

Impact of the 2018 ACR Supplemental Screening Recommendations on MRI Eligibility in Breast Cancer Survivors.

PURPOSE: The 2018 ACR recommendations for breast cancer screening in women at higher than average risk include new recommendations for supplemental breast MRI for patients with personal histories of breast cancer (PHBCs) who carry hereditary cancer gene mutations, have dense breast tissue, or were diagnosed before 50 years of age. In comparison, prior guidelines recommended supplemental MRI only for women with PHBCs who carried hereditary cancer gene mutations. The aim of this study was to quantify the increase in the number of patients with breast cancer for whom supplemental breast MRI would now be recommended. METHODS: Data were extracted from the electronic health records of patients presenting for screening or diagnostic mammography at an urban academic medical center between July 20, 2020, and July 19, 2021. Data extracted included patient-reported PHBC, age at time of breast cancer diagnosis, and hereditary cancer gene mutation carrier status. Descriptive statistics are reported, evaluating the rate of eligibility for supplemental breast MRI in a retrospective population given the new ACR guidelines. RESULTS: Of the 2,950 patients with self-reported PHBCs who presented for breast cancer screening in the year between July 2020 and July 2021, 1,805 (61%) met the criteria for supplemental breast MRI according to the 2018 guidelines compared with only 3.6% using pre-2018 guidelines. CONCLUSIONS: Measuring the impact of the 2018 ACR supplemental MRI recommendations using real-world data at a single urban academic medical center demonstrated a 15-fold increase in potential eligibility for supplemental breast MRI in patients with PHBCs.

Tumor Mutational Burden as a Predictor of First-Line Immune Checkpoint Inhibitor Versus Carboplatin Benefit in Cisplatin-Unfit Patients With Urothelial Carcinoma.

PURPOSE: In real-world settings, patients with metastatic urothelial carcinoma (mUC) are often more frail than clinical trials, underscoring an unmet need to identify patients who might be spared first-line chemotherapy. We sought to determine whether tumor mutational burden (TMB) identifies patients with comparable or superior clinical benefit of first-line single-agent immune checkpoint inhibitors (ICPI) in real-world patients deemed cisplatin-unfit. METHODS: Patients with mUC treated in first-line advanced setting (N = 401) received ICPI (n = 245) or carboplatin regiment without ICPI (n = 156) at physician's discretion in standard-of-care settings across approximately 280 US academic or community-based cancer clinics between March 2014 and July 2021. Deidentified data were captured into a real-world clinicogenomic database. All patients underwent testing using Foundation Medicine assays. Progression-free survival (PFS), time to next treatment (TTNT), and overall survival (OS) comparing ICPI versus chemotherapy were adjusted for known treatment assignment imbalances using propensity scores. RESULTS: TMB ≥ 10 was detected in 122 of 401 (30.4%) patients. Among patients receiving ICPI, those with TMB ≥ 10 had more favorable PFS (HR, 0.59; 95% CI, 0.41 to 0.85), TTNT (HR, 0.59; 95% CI, 0.43 to 0.83), and OS (HR, 0.47; 95% CI, 0.32 to 0.68). Comparing ICPI versus carboplatin, adjusting for imbalances, patients with TMB ≥ 10 had more favorable PFS (HR, 0.51; 95% CI, 0.32 to 0.82), TTNT (HR, 0.56; 95% CI, 0.35 to 0.91), and OS (HR, 0.56; 95% CI, 0.29 to 1.08) on ICPI versus chemotherapy, but not TMB < 10. Comparisons unadjusted for imbalances had similar associations. CONCLUSIONS: In real-world settings, mUC patients with TMB ≥ 10 have more favorable outcomes on first-line single-agent ICPI than carboplatin, adding clinical validity to TMB assessed by an existing US Food and Drug Administration-approved platform.

Black Women Are Less Likely to Be Classified as High-Risk for Breast Cancer Using the Tyrer-Cuzick 8 Model.

BACKGROUND: Breast cancer risk assessment is a powerful tool that guides recommendations for supplemental breast cancer screening and genetic counseling. The Tyrer-Cuzick 8 (TC8) model is widely used for calculating breast cancer risk and thus helps determine if women qualify for supplemental screening or genetic counseling. However, the TC8 model may underestimate breast cancer risk in Black women. This study sought to assess this disparity. METHODS: Data on race, breast density, body mass index (BMI), and TC8 scores were retrospectively extracted from the electronic medical record (EMR). Logistic regressions were run to evaluate racial differences in TC8 scores. Summary and correlation statistics determined relationships between BMI, breast density, and race. Rank biserial correlations were employed to explore the impact of breast density and BMI on TC8 scores. RESULTS: Of 15,356 patients, 5796 were White and 5813 were Black. Black patients had higher rates of BMI ≥ 27 compared with White women (79.2% vs. 45.7%), lower rates of breast density (35.1% vs. 56.2%), and lower rates of high-risk TC8 scores (10.7% vs. 17.5%, OR = 1.6646). There was an inverse relationship between TC8 score and BMI (rrb = - 0.04) and a direct relationship between TC8 score and breast density (rrb = 0.37). DISCUSSION: Black women are less likely to have high-risk TC8 scores despite having only marginally lower breast cancer incidence rates and higher breast cancer mortality rates than White women. This suggests that the TC8 model underestimates breast cancer risk in Black women, possibly due to lower rates of breast density and higher BMIs among Black women.

Variable Genomic Landscapes of Advanced Melanomas with Heavy Pigmentation.

BACKGROUND: In the current study, we examined the real-world prevalence of highly pigmented advanced melanomas (HPMel) and the clinicopathologic, genomic, and ICPI biomarker signatures of this class of tumors. MATERIALS AND METHODS: Our case archive of clinical melanoma samples for which the ordering physician requested testing for both PD-L1 immunohistochemistry (IHC) and comprehensive genomic profiling (CGP) was screened for HPMel cases, as well as for non-pigmented or lightly pigmented advanced melanoma cases (LPMel). RESULTS: Of the 1268 consecutive melanoma biopsies in our archive that had been submitted for PD-L1 IHC, 13.0% (165/1268) were HPMel and 87.0% (1103/1268) were LPMel. In the HPMel cohort, we saw a significantly lower tumor mutational burden (TMB, median 8.8 mutations/Mb) than in the LPMel group (11.4 mut/Mb), although there was substantial overlap. In examining characteristic secondary genomic alterations (GA), we found that the frequencies of GA in TERTp, CDKN2A, TP53, and PTEN were significantly lower in the HPMel cases than in LPMel. A higher rate of GA in CTNNB1, APC, PRKAR1A, and KIT was identified in the HPMel cohort compared with LPMel. CONCLUSIONS: In this study, we quantified the failure rates of melanoma samples for PD-L1 testing due to high melanin pigmentation and showed that CGP can be used in these patients to identify biomarkers that can guide treatment decisions for HPMel patients. Using this practical clinical definition for tumor pigmentation, our results indicate that HPMel are frequent at 13% of melanoma samples, and in general appear molecularly less developed, with a lower TMB and less frequent secondary GA of melanoma progression.

Digital Health Applications in Oncology: An Opportunity to Seize.

Digital health advances have transformed many clinical areas including psychiatric and cardiovascular care. However, digital health innovation is relatively nascent in cancer care, which represents the fastest growing area of health-care spending. Opportunities for digital health innovation in oncology include patient-facing technologies that improve patient experience, safety, and patient-clinician interactions; clinician-facing technologies that improve their ability to diagnose pathology and predict adverse events; and quality of care and research infrastructure to improve clinical workflows, documentation, decision support, and clinical trial monitoring. The COVID-19 pandemic and associated shifts of care to the home and community dramatically accelerated the integration of digital health technologies into virtually every aspect of oncology care. However, the pandemic has also exposed potential flaws in the digital health ecosystem, namely in clinical integration strategies; data access, quality, and security; and regulatory oversight and reimbursement for digital health technologies. Stemming from the proceedings of a 2020 workshop convened by the National Cancer Policy Forum of the National Academies of Sciences, Engineering, and Medicine, this article summarizes the current state of digital health technologies in medical practice and strategies to improve clinical utility and integration. These recommendations, with calls to action for clinicians, health systems, technology innovators, and policy makers, will facilitate efficient yet safe integration of digital health technologies into cancer care.

Association of CD274 (PD-L1) Copy Number Changes with Immune Checkpoint Inhibitor Clinical Benefit in Non-Squamous Non-Small Cell Lung Cancer.

BACKGROUND: We sought to characterize response to immune checkpoint inhibitor (ICI) in non-squamous non-small cell lung cancer (NSCLC) across various CD274 copy number gain and loss thresholds and identify an optimal cutoff. MATERIALS AND METHODS: A de-identified nationwide (US) real-world clinico-genomic database was leveraged to study 621 non-squamous NSCLC patients treated with ICI. All patients received second-line ICI monotherapy and underwent comprehensive genomic profiling as part of routine clinical care. Overall survival (OS) from start of ICI, for CD274 copy number gain and loss cohorts across varying copy number thresholds, were assessed. RESULTS: Among the 621 patients, patients with a CD274 CN greater than or equal to specimen ploidy +2 (N = 29) had a significantly higher median (m) OS when compared with the rest of the cohort (N = 592; 16.1 [8.9-37.3] vs 8.6 [7.1-10.9] months, hazard ratio (HR) = 0.6 [0.4-1.0], P-value = .05). Patients with a CD274 copy number less than specimen ploidy (N = 299) trended toward a lower mOS when compared to the rest of the cohort (N = 322; 7.5 [5.9-11.3] vs 9.6 [7.9-12.8] months, HR = 0.9 [0.7-1.1], P-value = .3). CONCLUSION: This work shows that CD274 copy number gains at varying thresholds predict different response to ICI blockade in non-squamous NSCLC. Considering these data, prospective clinical trials should further validate these findings, specifically in the context of PD-L1 IHC test results.

Comparative Effectiveness of Immune Checkpoint Inhibitors vs Chemotherapy by Tumor Mutational Burden in Metastatic Castration-Resistant Prostate Cancer.

Importance: The most useful biomarkers for clinical decision-making identify patients likely to have improved outcomes with one treatment vs another. Objective: To evaluate treatment class-specific outcomes of patients receiving immune checkpoint inhibitor (ICI) vs taxane chemotherapy by tumor mutational burden (TMB). Design, Setting, and Participants: This comparative effectiveness analysis of clinical variables and outcomes used prospectively defined biomarker-stratified genomic data from a deidentified clinicogenomic database. Data included men with previously treated metastatic castration-resistant prostate cancer (mCRPC) receiving ICI or single-agent taxane chemotherapy from January 2011 to April 2021 at approximately 280 US academic or community-based cancer clinics (approximately 800 sites of care). Data were analyzed from July to August 2021. Exposures: Single-agent ICI or single-agent taxanes. Treatments were assigned at discretion of physician and patient without randomization. Imbalances of known factors between treatment groups were adjusted with propensity weighting. Main Outcomes and Measures: Prostate-specific antigen (PSA) response, time to next therapy (TTNT), and overall survival (OS). Results: A total of 741 men (median [IQR], 70 [64-76] years) with mCRPC received comprehensive genomic profiling and were treated with ICI or single-agent taxane therapy. At baseline, the median (IQR) PSA level was 79.4 (19.0-254) ng/mL, 108 men (18.8%) had Eastern Cooperative Oncology Group Performance Status scores of 2 or greater, and 644 men (86.9%) had received prior systemic treatments for mCRPC. A total of 45 patients (6.1%) received ICI therapy and 696 patients (93.9%) received taxane therapy. Among patients with TMB of fewer than 10 mutations per megabase (mt/Mb) receiving ICI, compared with those receiving taxanes, had worse TTNT (median [IQR], 2.4 [1.1-3.2] months vs 4.1 [2.2-6.3] months; hazard ratio [HR], 2.65; 95% CI, 1.78-3.95; P < .001). In contrast, for patients with TMB of 10 mt/Mb or greater, use of ICIs, compared with use taxanes, was associated with more favorable TTNT (median [IQR], 8.0 [3.4 to unknown] months vs 2.4 [2.4-7.3] months; HR, 0.37, 95% CI, 0.15-0.87; P = .02) and OS (median 19.9 [8.06 to unknown] months vs 4.2 [2.69 - 6.12] months; HR, 0.23; 95% CI, 0.10-0.57; P = .001). Among all 741 patients, 44 (5.9%) had TMB of 10 mt/Mb or greater, 22 (3.0%) had high microsatellite instability, and 20 (2.7%) had both. Treatment interactions with TMB of 10 mt/Mb or greater (TTNT: HR, 0.10; 95% CI, 0.32-0.31; P < .001; OS: HR, 0.25; 95% CI, 0.076-0.81; P = .02) were stronger than high microsatellite instability alone (TTNT: HR, 0.12; 95% CI, 0.03-0.51; P = .004; OS: HR, 0.38; 95% CI, 0.13-1.12; P = .08). Conclusions and Relevance: In this comparative effectiveness study, ICIs were more effective than taxanes in patients with mCRPC when TMB was 10 mt/Mb or greater but not when TMB was fewer than 10 mt/Mb. The results add validity to the existing TMB cutoff of 10 mt/Mb for ICI use in later lines of therapy, and suggest that ICIs may be a viable alternative to taxane chemotherapy for patients with mCRPC with high TMB.

Natural History and Characteristics of ERBB2-mutated Hormone Receptor-positive Metastatic Breast Cancer: A Multi-institutional Retrospective Case-control Study from AACR Project GENIE.

PURPOSE: We wanted to determine the prognosis and the phenotypic characteristics of hormone receptor-positive advanced breast cancer tumors harboring an ERBB2 mutation in the absence of a HER2 amplification. EXPERIMENTAL DESIGN: We retrospectively collected information from the American Association of Cancer Research-Genomics Evidence Neoplasia Information Exchange registry database from patients with hormone receptor-positive, HER2-negative, ERBB2-mutated advanced breast cancer. Phenotypic and co-mutational features, as well as response to treatment and outcome were compared with matched control cases ERBB2 wild type. RESULTS: A total of 45 ERBB2-mutant cases were identified for 90 matched controls. The presence of an ERBB2 mutation was not associated with worse outcome determined by overall survival (OS) from first metastatic relapse. No significant differences were observed in phenotypic characteristics apart from higher lobular infiltrating subtype in the ERBB2-mutated group. ERBB2 mutation did not seem to have an impact in response to treatment or time-to-progression (TTP) to endocrine therapy compared with ERBB2 wild type. In the co-mutational analyses, CDH1 mutation was more frequent in the ERBB2-mutated group (FDR < 1). Although not significant, fewer co-occurring ESR1 mutations and more KRAS mutations were identified in the ERBB2-mutated group. CONCLUSIONS: ERBB2-activating mutation was not associated with a worse OS from time of first metastatic relapse, or differences in TTP on treatment as compared with a series of matched controls. Although not significant, differences in coexisting mutations (CDH1, ESR1, and KRAS) were noted between the ERBB2-mutated and the control group.

Preferences in Oncology History Documentation Styles Among Clinical Practitioners.

PURPOSE: Clinical notes function as the de facto handoff between providers and assume great importance during unplanned medical encounters. An organized and thorough oncology history is essential in care coordination. We sought to understand reader preferences for oncology history organization by comparing between chronologic and narrative formats. METHODS: A convenience sample of 562 clinicians from 19 National Comprehensive Cancer Network Member Institutions responded to a survey comparing two formats of oncology histories, narrative and chronologic, for the same patient. Both histories were consensus-derived real-world examples. Each history was evaluated using semantic differential attributes (thorough, useful, organized, comprehensible, and succinct). Respondents choose a preference between the two styles for history gathering and as the basis of a new note. Open-ended responses were also solicited. RESULTS: Respondents preferred the chronologic over the narrative history to prepare for a visit with an unknown patient (66% preference) and as a basis for their own note preparation (77% preference) (P < .01). The chronologic summary was preferred in four of the five measured attributes (useful, organized, comprehensible, and succinct); the narrative summary was favored for thoroughness (P < .01). Open-ended responses reflected the attribute scoring and noted the utility of content describing social determinants of health in the narrative history. CONCLUSION: Respondents of this convenience sample preferred a chronologic oncology history to a concise narrative history. Further studies are needed to determine the optimal structure and content of chronologic documentation for oncology patients and the provider effort to use this format.

My Cancer Genome: Coevolution of Precision Oncology and a Molecular Oncology Knowledgebase.

PURPOSE: The My Cancer Genome (MCG) knowledgebase and resulting website were launched in 2011 with the purpose of guiding clinicians in the application of genomic testing results for treatment of patients with cancer. Both knowledgebase and website were originally developed using a wiki-style approach that relied on manual evidence curation and synthesis of that evidence into cancer-related biomarker, disease, and pathway pages on the website that summarized the literature for a clinical audience. This approach required significant time investment for each page, which limited website scalability as the field advanced. To address this challenge, we designed and used an assertion-based data model that allows the knowledgebase and website to expand with the field of precision oncology. METHODS: Assertions, or computationally accessible cause and effect statements, are both manually curated from primary sources and imported from external databases and stored in a knowledge management system. To generate pages for the MCG website, reusable templates transform assertions into reconfigurable text and visualizations that form the building blocks for automatically updating disease, biomarker, drug, and clinical trial pages. RESULTS: Combining text and graph templates with assertions in our knowledgebase allows generation of web pages that automatically update with our knowledgebase. Automated page generation empowers rapid scaling of the website as assertions with new biomarkers and drugs are added to the knowledgebase. This process has generated more than 9,100 clinical trial pages, 18,100 gene and alteration pages, 900 disease pages, and 2,700 drug pages to date. CONCLUSION: Leveraging both computational and manual curation processes in combination with reusable templates empowers automation and scalability for both the MCG knowledgebase and MCG website.

Landscape Analysis of Breast Cancer and Acute Myeloid Leukemia Trials Using the My Cancer Genome Clinical Trial Data Model.

PURPOSE: The field of oncology is expanding rapidly. New trials are opening as an increasing number of therapeutic agents are being investigated before they can become approved therapies. Aggregate views of these data, particularly data associated with diseases, biomarkers, and drugs, can be helpful in understanding the trends in current research as well as existing gaps in cancer care. METHODS: In this paper, we performed a landscape analysis for breast cancer and acute myeloid leukemia related trials with structured, curated data from clinical trials using the My Cancer Genome clinical trial knowledgebase. RESULTS: We have performed detailed analytics on breast cancer (N = 1,128) and acute myeloid leukemia trial sets (N = 483) to highlight the top biomarkers, drug classes, and drugs-thereby supporting a full view of biomarkers, biomarker groups, and drugs that are currently being explored in these respective diseases. CONCLUSION: Analysis and data visualization of the cancer clinical trial landscape can inform strategic planning for new trial designs and trial activation at a particular site.

An Analysis of Electronic Health Record Work to Manage Asynchronous Clinical Messages among Breast Cancer Care Teams.

OBJECTIVE: Asynchronous messaging is an integral aspect of communication in clinical settings, but imposes additional work and potentially leads to inefficiency. The goal of this study was to describe the time spent using the electronic health record (EHR) to manage asynchronous communication to support breast cancer care coordination. METHODS: We analyzed 3 years of audit logs and secure messaging logs from the EHR for care team members involved in breast cancer care at Vanderbilt University Medical Center. To evaluate trends in EHR use, we combined log data into sequences of events that occurred within 15 minutes of any other event by the same employee about the same patient. RESULTS: Our cohort of 9,761 patients were the subject of 430,857 message threads by 7,194 employees over a 3-year period. Breast cancer care team members performed messaging actions in 37.5% of all EHR sessions, averaging 29.8 (standard deviation [SD] = 23.5) messaging sessions per day. Messaging sessions lasted an average of 1.1 (95% confidence interval: 0.99-1.24) minutes longer than nonmessaging sessions. On days when the cancer providers did not otherwise have clinical responsibilities, they still performed messaging actions in an average of 15 (SD = 11.9) sessions per day. CONCLUSION: At our institution, clinical messaging occurred in 35% of all EHR sessions. Clinical messaging, sometimes viewed as a supporting task of clinical work, is important to delivering and coordinating care across roles. Measuring the electronic work of asynchronous communication among care team members affords the opportunity to systematically identify opportunities to improve employee workload.

Breast Cancer Disparities Through the Lens of the COVID-19 Pandemic.

Purpose of Review: The emergency medicine and critical care needs of the COVID-19 pandemic forced a sudden and dramatic disruption of cancer screening and treatment programs in the USA during the winter and spring of 2020. This review commentary addresses the impact of the pandemic on racial/ethnic minorities such as African Americans and Hispanic-Latina Americans, with a focus on factors related to breast cancer. Recent Findings: African Americans and Hispanic-Latina Americans experienced disproportionately higher morbidity and mortality from COVID-19; many of the same socioeconomic and tumor biology/genetic factors that explain breast cancer disparities are likely to account for COVID-19 outcome disparities. Summary: The breast cancer clinical and research community should partner with public health experts to ensure participation of diverse patients in COVID-19 treatment trials and vaccine programs and to overcome COVID-19-related breast health management delays that are likely to have been magnified among African Americans and Hispanic-Latina Americans.

Non-secretory multiple myeloma with unusual TFG-ALK fusion showed dramatic response to ALK inhibition.

Non-secretory multiple myeloma (NSMM) constitutes a distinct entity of multiple myeloma characterized by the absence of detectable monoclonal protein and rarely an absence of free light chains in the serum and urine. Given its rarity, the genomic landscape, clinical course, and prognosis of NSSM are not well characterized. Here, we report a case of a patient with relapsed and refractory NSMM with brain metastasis harboring a TFG-ALK fusion showing a dramatic and durable (over two years) response to commercially available anaplastic lymphoma kinase (ALK) inhibitors. The case emphasizes the beneficial role of molecular profiling in this target-poor disease.

Learnings From Precision Clinical Trial Matching for Oncology Patients Who Received NGS Testing.

PURPOSE: Tumor next-generation sequencing reports typically generate trial recommendations for patients based on their diagnosis and genomic profile. However, these require additional refinement and prescreening, which can add to physician burden. We wanted to use human prescreening efforts to efficiently refine these trial options and also elucidate the high-value parameters that have a major impact on efficient trial matching. METHODS: Clinical trial recommendations were generated based on diagnosis and biomarker criteria using an informatics platform and were further refined by manual prescreening. The refined results were then compared with the initial trial recommendations and the reasons for false-positive matches were evaluated. RESULTS: Manual prescreening significantly reduced the number of false positives from the informatics generated trial recommendations, as expected. We found that trial-specific criteria, especially recruiting status for individual trial arms, were a high value parameter and led to the largest number of automated false-positive matches. CONCLUSION: Reflex clinical trial matching approaches that refine trial recommendations based on the clinical details as well as trial-specific criteria have the potential to help alleviate physician burden for selecting the most appropriate trial for their patient. Investing in publicly available resources that capture the recruiting status of a trial at the cohort or arm level would, therefore, allow us to make meaningful contributions to increase the clinical trial enrollments by eliminating false positives.