bluuebunny/crossref_metadata_2025 huggingface dataset:
Associations between HIV infection status, psychosocial factors, and adjuvant endocrine therapy adherence among South African women with early-stage breast cancer.
Authors: O'Neil Daniel , Blanchard Charmaine , Ream Molly , Mmoledi Keletso , Mkwanazi Nontlantla , Shandukani Victor , Ruff Paul , Antoni Michael , Joffe Maureen
Published: May 2024

522

Background: South African (SA) women living with comorbid estrogen receptor positive (ER+) breast cancer (BC) and HIV have higher mortality than other SA women with ER+ BC. We aimed to evaluate for associations between HIV status, psychosocial factors, and adjuvant endocrine therapy (AET) adherence as a potential contributor to this disparity. Methods: From Chris Hani Baragwanath Hospital, Johannesburg, we enrolled adult women with stage I-III ER+ BC in remission and currently prescribed tamoxifen or an aromatase inhibitor to a prospective cohort study. We performed AET pill counts at enrollment, 12 weeks, and 24 weeks, and calculated adherence ratios from the difference in pills between visits divided by the number of days between visits. Women completed questionnaires on sources of social support, beliefs about medication, health literacy, and self-efficacy at enrollment and questionnaires about mental health (depression, anxiety, and acute stress) symptom burden and AET-related side effects at the 12- and 24-week visits. We also collected household wealth data and clinical data on BC and HIV. AET adherence ratios were compared between women with and without comorbid HIV using Wilcoxon rank sum testing. We also used structural equation modeling techniques to refine and evaluate an a priori model of AET adherence with latent variables for mental health, socioeconomic (SES) status, healthcare savvy, and AET side effect burden and subgroup analyses of the resulting model in women with and without HIV. Results: Between April 26, 2022, and July 11, 2023, we enrolled 239 women, 63 (26.4%) of whom had co-morbid HIV. Adherence data was available from 106 women at 12 and 24 weeks, from 22 women at 12 weeks only, and from 111 women at 24 weeks only. Comparing women with and without HIV, median AET adherence ratio was 0.88 vs 0.89, respectively (p = 0.65). Our final model of AET adherence achieved good fit (comparative fit index = 0.96, RMSEA 90% CI: 0.03-0.06). In the full cohort, SES quintile showed a trend towards association with AET adherence (β 0.02, SE 0.01, p=0.09); mental health, healthcare savvy, and side effect burden latent variables were not significantly associated with adherence. In the subgroup of women living with HIV, SES quintile (β 0.04, SE 0.02, p=0.08) and mental health (β -0.02, SE 0.01, p=0.10) showed trends toward association with adherence; these relationships did not persist for women without HIV. Conclusions: HIV status is not predictive of AET adherence among SA women with ER+ BC, but in women with both diagnoses, decreasing SES status and increasing mental health symptoms trended towards an association with decreased adherence. Interventions to improve the mental health of SA breast cancer patients living with HIV may promote AET adherence.
Use of chemotherapy and loco-regional therapy for stage IA triple-negative breast cancer and their association with oncologic outcomes: A cancer registry study.
Authors: Pfob André , Surovtsova Irina , Kokh Daria , Heil Jörg , Banys-Paluchowski Maggie , Morakis Philipp ,   KRBW (Krebsregister Baden-Wuerttemberg)
Published: May 2024

524

Background: We aimed to evaluate the role of adjuvant chemotherapy and loco-regional therapy for stage IA (pT1, pN0) triple-negative breast cancer (TNBC) in a real-world setting. Methods: We identified patients with pT1, pN0 TNBC diagnosed between 2009 and 2021 within the clinical cancer registry of Baden-Wuerttemberg, Germany. Overall survival (OS) was assessed using Kaplan-Meier statistics and multivariate Cox regression models (adjusted for age, use of chemotherapy, local therapy (breast conserving therapy [breast conserving surgery + radiotherapy] vs. mastectomy), and tumor histologic subtype). Results: A total of 1191 patients with a median follow-up of 43.8 months were identified: 0.9% (11 of 1191) with pT1mi stage, 10.0% (119 of 1191) with pT1a, 24.0% (286 of 1191) with pT1b, and 65.0% (775 of 1191) with pT1c. Use of adjuvant chemotherapy was 9.1% (1 of 11) in pT1mi stage, 41.2% (49 of 119) in pT1a, 66.8% (191 of 286) in pT1b, and 69.8% (541 of 775) in pT1c. Multivariate Cox regression analysis revealed no significant influence for the use of adjuvant chemotherapy on OS in pT1a and pT1b patients (for pT1a HR 1.27, 95% CI 0.19 to 8.50, for pT1b HR 1.07, 95% CI 0.50 to 2.30) but for patient age in the pT1b group (HR 4.71, 95% CI 2.26 to 9.8, for age ≥70 vs. <70 years). For pT1c patients, there was significant influence for the use of adjuvant chemotherapy on OS (HR 0.55, 95% CI 0.38 to 0.8), for local therapy (HR 0.41, 95% 0.25 to 0.69, for breast conserving therapy vs. mastectomy only), and patient age (HR 2.33, 95% CI 1.61 to 3.39 for age ≥70 vs. <70 years). Notably, for pT1c patients aged <70years, local therapy (HR 0.32, 95% CI 0.15-0.69), in favor of breast conserving therapy) but not use of chemotherapy (HR 1.11, 95% CI 0.56-2.19) was associated with OS. Conclusions: This data suggests that OS in stage IA TNBC is strongly influenced by local therapy and patient age, but not use of chemotherapy. Larger studies with longer-term follow-up are welcomed to fully inform this discussion.
PARPi eligibility amongst women with newly diagnosed invasive breast cancer enrolled in the GREAT universal genetic testing study.
Authors: Wong Stephanie M. , Rezoug Zoulikha , Totten Stephanie P , Szlachtycz David M , Atayan Adrienne M , Mohler Kristen , Albert Sophie , Feng Leila , Lemieux Anglin Brianna , Shen Zhen , Hamel Nancy , Meti Nicholas , Esfahani Khashayar , Anderson Dawn , Boileau Jean-Francois , Prakash Ipshita , Basik Mark , Meterissian Sarkis H. , Chong George , Foulkes William D. ,   GREAT AGATA Study Group
Published: May 2024

531

Background: Poly(ADP-ribose) polymerase inhibitors (PARPi) are approved for the treatment of BRCA-associated metastatic and high-risk early breast cancer. Recent guidelines have endorsed the use of BRCA1/2 testing for all patients with breast cancer who may be eligible for PARPi therapy, however it is unclear what proportion of patients are impacted by these recommendations. Methods: We sought to evaluate pre-test and post-test eligibility for PARPi in women aged >18 years old with a first diagnosis of stage I-IV invasive breast cancer who enrolled in a prospective, multicentered universal genetic testing study between 2019-2022. All enrolled patients underwent pre-test counselling and an obligatory primary panel of BRCA1, BRCA2, and PALB2 at the time of diagnosis. Candidacy for PARPi was determined by biologic subtype, clinical stage, pathologic stage, and/or response to neoadjuvant chemotherapy. Results: Of 1017 patients referred for the study, 805 were eligible and 729 (90.6%) consented to participate. The median age at diagnosis was 53 years (IQR, 45-62 years) and 96.2% had stage I-III disease. Overall, 32 (4.4%) patients had a germline pathogenic variant (GPV) in BRCA1/2, and 7 (1.0%) had a GPV in PALB2. Of 112 (15.4%) patients with triple negative breast cancer (TNBC), 19.6% had a GPV in BRCA1/2 or PALB2, whereas in 487 (66.8%) with ER+HER2- disease, 2.9% had a GPV (p<0.001). Among the 112 patients with TNBC, 64 (57%) were candidates for PARPi pre-genetic testing, and 12 (10.7%) remained eligible due to a GPV in BRCA1/2. Among the 487 patients with ER+HER2- breast cancer, 37 (5.1%) were candidates for PARPi pre-genetic testing, and 1 (0.2%) remained eligible due to a BRCA1 GPV identified on testing. All patients who were PARPi eligible were <65 years of age or >65 years with TNBC. Conclusions: In women with newly diagnosed invasive breast cancer, approximately 14% are candidates for PARPi prior to genetic testing, and 1.8% remain PARPi eligible due to a confirmed pathogenic variant in BRCA1/2. Consequently, genetic testing impacts systemic therapy decisions for PARPi in 10% of TNBC patients and fewer than 1% of women with ER+HER2- breast cancer. [Table: see text]
Effects of plant-based diet (PBD) and exercise therapy (Ex) on weight and body composition in patients with primary hormone receptor (HR) positive breast cancer: A phase 2 randomized controlled trial.
Authors: Iyengar Neil M. , Salehi Erica , Lavery Jessica A , Chan Olivia , Lehman Sarah , Michalski Meghan G. , Fickera Gina , Carlson Adele , Harrison Jenna , Underwood Whitney P. , Anselmo Cara , Chun Su , Cao Stephanie , Lee Catherine P. , Demark-Wahnefried Wendy , Moskowitz Chaya S. , Jones Lee W.
Published: May 2024

548

Background: Obesity increases breast cancer recurrence and mortality. Strategies that induce weight loss may improve clinical outcomes. We investigated the feasibility and efficacy of personalized energy restricted PBD plus Ex on weight and body composition in primary HR-positive breast cancer (NCT04298086). Methods: Postmenopausal women with body mass index (BMI) ≥ 27 kg/m2 on adjuvant endocrine therapy were randomized (1:1) to PBD plus Ex or attention control for 24 weeks. PBD plus Ex received individualized caloric goals adjusted weekly to target 1.5 lbs/week weight loss. PBD targeted 500 kcal/day goal deficit achieved via nutrition coaching and meal delivery. Ex sessions targeted 250 kcal goal expenditure via remotely delivered treadmill walking 3-5 days/week with real-time monitoring. Attention control received a home treadmill and monthly check-in calls. Baseline to post-intervention changes in weight and body composition, measured by dual energy X-ray absorptiometry (DXA), were compared between arms using linear mixed models. Results: 43 women were randomized between 8/2020 and 4/2023. Weight data was available for all participants (35 measured at follow-up, 8 abstracted from clinical documentation); 37 completed post-intervention DXA. At baseline, mean BMI was 34 (SD 4) kg/m2. Intention-to-treat results are presented in the Table. Mean weight loss in PBD plus Ex was –13% (SD 6%) compared with –5% (SD 6%) in attention control (mean between group difference –8 kg, 95% CI –11, –4). Mean fat loss in PBD plus Ex was –6 kg compared with –2 kg in attention control (mean between group difference –4 kg, 95% CI –6, –2). Lean mass increases were greater in PBD plus Ex (P<0.001). Weekly energy deficit goal compliance was 95% in month 1 and 64% in month 6. No serious adverse events were observed. Baseline and post-intervention tissue samples were available on 37 (86%) patients, which will undergo biologic correlative analysis. Conclusions: Personalized PBD plus Ex led to substantial weight loss and favorable changes in body composition during endocrine therapy for HR-positive breast cancer. Clinical trial information: NCT04298086 . [Table: see text]
Determinants of pathological complete response and tumor regression in high-risk breast cancer treated with neoadjuvant radiotherapy and chemotherapy.
Authors: Haussmann Jan , Budach Wilfried , Nestle Kraemling Carolin , Wollandt Sylvia , Jazmati Danny , Tamaskovics Balint , Corradini Stefanie , Boelke Edwin , Haussmann Alexander , Audretsch Werner , Matuschek Christiane
Published: May 2024

e12652

Background: Pathological complete response (pCR) is a recognized prognostic indicator in breast cancer patients undergoing neoadjuvant systemic therapy (naST). Known determinants of pCR include intrinsic subtype, proliferation index, grading, clinical tumor and nodal stage, as well as the type of systemic therapy. Incorporating neoadjuvant radiotherapy (naRT) may enhance response rates, disease-free survival, toxicity profiles, and cosmetic outcomes compared to adjuvant radiotherapy. However, the factors influencing pCR and primary tumor regression with the addition of neoadjuvant radiotherapy to chemotherapy are not well-documented. Methods: A retrospective analysis was conducted on 341 patients (cT1-cT4/cN0-N+) who received naRT and neoadjuvant chemotherapy between 1990 and 2003. Treatment included naRT to the breast and, in most cases, to the supra-/infraclavicular lymph nodes, complemented by an electron or brachytherapy boost. NaST was administered either sequentially or concurrently with RT, utilizing various regimens. Univariate and multivariate regression analyses were employed to evaluate the impact of different subgroups and treatment modalities on pCR (ypT0/Tis and ypN0) and complete primary tumor response (ypT0/Tis). Receiver operating characteristic (ROC) analysis assessed the interval between radiotherapy (RT) and surgical resection (Rx), as well as the radiotherapy dose. Results: Out of 341 analyzed patients, 31.1% achieved pCR. Multivariate analysis revealed that pCR rates were affected by the planned type of resection, breast cancer subtype, primary tumor stage, and the interval between radiation and surgery. The biologically effective dose to the tumor did not significantly impact pCR. Univariate analysis identified age, resection type, breast cancer subtype, clinical tumor stage, and grading as significant factors for primary tumor regression. In the multivariate analysis, resection type, subtype, and clinical tumor stage remained significant. Radiation dose to the tumor and the interval from radiation to surgery were not significant for pCR. However, a longer interval from radiotherapy to resection significantly predicted pCR when treatment factors were included in the model. Conclusions: The factors associated with pCR following combined neoadjuvant chemotherapy and radiotherapy are akin to those identified with neoadjuvant chemotherapy alone. A prolonged interval to surgery may be linked to higher pCR rates. Escalating the dose beyond 60 Gy did not lead to increased response rates.
Utilization of PARP inhibitors in the management of ovarian cancer in Nigeria.
Authors: Akinsanya Precious , Akahara Darlington , Okoro Uchenna Samuel , Okonkwo Susan , Umeh Uchenna Anthony , Lasebikan Nwamaka , Uche Enoch , Okafor Adetoro , Olusunmade Oyindamola , Okehi Uchechi , Julemis Marsophia , Orimaye Sylvester
Published: May 2024

e13500

Background: Ovarian cancer remains a significant health concern globally, especially in countries with low Human Development Index (HDI), where there is a projected 96% increase in new cases and a 100% increase in associated deaths by 2040 compared to a 19% increase in new cases and a 28% increase in deaths in very High HDI countries. Over the years, significant strides have been made in the treatment of ovarian cancer, leading to a decrease in ovarian cancer-related mortality in High HDI countries. Poly (ADP-ribose) polymerase inhibitors (PARPi) are among the new and emerging treatment options, which have transformed the management of ovarian cancer, especially in patients with BRCA mutations. Methods: A cross-sectional survey was distributed to clinical and gynecologic oncologists practicing in Nigeria via email, text, WhatsApp, and telegram messaging. Clinical and gynecologic oncologists who are not involved in the treatment of patients with ovarian cancer and those who are not currently in practice were excluded. Results: Out of 36 respondents, 34 were analyzed. While PARP inhibitors are increasingly acknowledged (85.29% awareness), actual utilization remains modest (14.71%). The sole PARP inhibitor used is Olaparib. The majority of respondents (48.28%) who did not use PARP inhibitors cited both the lack of availability and the high cost of medications as the reasons. Key barriers to the use of PARP inhibitors include a combination of non-availability and cost (48.28%) and a combination of institutional protocols and socioeconomic status (20.59%). Conclusions: Despite increasing awareness, PARP inhibitor utilization in Nigerian ovarian cancer management is hindered by challenges, predominantly cost and availability. The study highlights a missed opportunity for optimizing advanced ovarian cancer treatment in Nigeria. [Table: see text]
Characterization of cancer clinical trials in the community setting.
Authors: Altomare Ivy , Lu Yichen , Pal Sumanta Kumar , Boehmer Leigh , Shivakumar Latha , Griffin Lyndsey , Demirhan Kimberly , Kisiel Molly , Oyer Randall A.
Published: May 2024

e13506

Background: Extending clinical trials to community oncology sites is an imperative to meet accrual goals, ensure generalizable results, and facilitate optimal and equitable clinical care. The types of trials attractive to and successful in the community, however, are likely different from those run primarily at academic centers. We analyzed the characteristics of clinical trials open at a network of community oncology practices across the United States in the last 2 years, in order to inform both sponsors and sites about the studies most well-suited for a community setting. Methods: We analyzed characteristics from every clinical trial entered in OncoTrials, a clinical trial screening and tracking tool utilized exclusively by US community oncology practices, between 9/1/2021 through 10/09/2023 via knowledge of the trial NCT number and data available through API from clinicaltrials.gov. Descriptive statistics, including median and range for continuous variables and percentages for categorical variables are reported. Results: 1,310 clinical trials were open across 64 community oncology practices. Sponsors were classified as 80% industry (n=1,054), 15% NIH (n=195), 1% network (n=13) and 5% other (n=48). 93% of studies were interventional, 5% observational, 1% registry and 1% expanded access. Types of interventional studies (n=1,215) and the number of sites that ran them are shown (Table). The median target enrollment across all studies was 235 patients. Individual trials were open at a median of 2 community practices in our cohort (range 1-22 practices); 521 clinical trials (40%) were open at only one practice and 34 trials (2.6%) were open at more than 10 practices. The mean number of unique trials open at a practice during our 2 year observation period was 54 (median 35, range 1-264). Among these trials, the most commonly associated tumor types were lung (15%), pan-solid tumors (14%), breast (11%), lymphoma (6%), colorectal (6%), prostate (5%), gynecologic (4%), bladder (4%), head and neck (4%) and melanoma (4%). Conclusions: Community oncology practices supported a robust portfolio of clinical trials, most commonly focused on treatment of solid tumors. The vast majority were interventional (phase 2-3) and industry-sponsored. Half of sites ran Phase I trials, and Phase IV trials were uncommon but had broad participation across sites. Notably, a large proportion of studies were only open at one single site in a cohort of 64 community oncology practices. This highlights the opportunity for sponsors to leverage networks, consortia, and further research to ensure that appropriate studies are accessible among a broader range of community research sites. [Table: see text]
Impact of preparation and execution of strategy to mitigate the platinum shortage within a network of community oncology practices.
Authors: Ginsburg Aimee , Dickens Andrea , Thornby Robert , Dominguez Kaci , Howell Josh , Busby Leslie T.
Published: May 2024

e13572

Background: The US Oncology Network (USON) is made up of over 600 sites of care and treats 1,400,000 patients annually. Drug shortages have a massive impact on patient outcomes, particularly with limited source oncology medications. Proactive mitigation strategies by the national USON Pharmacy & Therapeutics (P&T) committee are examined to assess impact on cisplatin and carboplatin (cis/carbo) shortages, where a phased approach extended supply for patients. Methods: P&T began implementing gradual reductions in cis/carbo allocations in mid-April 2023. This included stewardship to reserve use in patients with limited alternatives, dose rounding, reducing dose/cycle, and extending cycle interval, when clinically appropriate. As supply depletion became imminent, P&T implemented a novel drug ordering process that restricted cis/carbo use criteria to curative intent without alternative treatment options, requiring case-by-case approval. Comprehensive clinical guidance was developed to provide recommendations for alternative therapies. Alternative regimen templates were built into the centrally managed EHR. To evaluate the impact, drug utilization patterns were tracked during the 6-month shortage (April - September 2023) and compared to historical data. Results: Pronounced impacts were seen during acute supply constraints: cisplatin administrations (admins) and mg decreased to 53% and 48% of baseline, carboplatin admins and mg decreased to 84% and 78%. Compared to the prior 6 months, patients receiving cis/carbo was similar pre-shortage (15,368) vs. during (15,296).Mitigation strategies resulted in preservation of cis/carbo admins for diseases with limited alternatives (NSCLC, head & neck, ovarian/uterine); other cancers with alternatives had a decrease in admins (see table). Dose conservation guidance led to a decrease in average mg administered by 5.1% for cisplatin (72.2 vs. 68.5), and 6.2% for carboplatin (385.5 vs. 361.7). New admins of oxaliplatin increased by 11% (4,230 vs 4,714), primarily in GI malignancies. Conclusions: The rigors of stewardship with a phased approach allowed USON to sustain new patients while conserving cis/carbo for those with limited alternatives. Frequent communication about supply status and conservation guidance was critical for transition to alternative treatment strategies. This experience tested USON organizational readiness for future shortages. [Table: see text]
Perspectives on clinical adoption barriers to blood-based multi-cancer early detection tests across stakeholders.
Authors: Schroll Monica M , Quinn Elissa , Pritchard Daryl , Chang Allina , Garner Amanti Kristen , Perez Omar , Agarwal Arushi , Gustavsen Gary George
Published: May 2024

e13574

Background: Current United States Preventive Services Task Force (USPSTF) recommendations include routine screening for breast, cervical, colorectal, and lung cancer; however, two out of every three cancer cases occur in other indications leading to diagnosis in advanced stages of the disease and higher likelihood of mortality. Current recommended cancer screening and early detection tests also face several hurdles hindering equitable access in a real-world setting. Blood-based MCED tests can impact cancer screening and early detection by monitoring for multiple different cancer types at once via a blood draw that can detect cancers in multiple indications, including indications where screening is not performed routinely today. Given their nascency, the role of blood-based MCED tests in clinical practice is currently undefined. To help facilitate the appropriate integration of MCED tests into patient care, it is important to understand the perspectives of stakeholders on the anticipated challenges to implementation. Methods: We conducted three separate double-blinded surveys in July 2023 of representative cohorts of U.S. Healthcare providers (HCPs) (n=238) that are or act as primary care providers (general practitioners and obstetrics and gynecologists (OB-GYNs)), payers (n=40), and patients (n=116), to evaluate the current cancer screening and early detection landscape and gather perspectives on barriers to implementation of new cancer screening technologies, including blood-based MCED tests. Results: Of the surveyed HCPs and payers, >90% and 100% respectively reported to be aware of MCED tests. However, <10% of HCPs reported having ordered an MCED test and 80% of payers had not yet evaluated an MCED test for coverage under their plan at the time of the survey. The survey results indicated that there is broad agreement on the value proposition that blood-based MCED tests would improve patient outcomes with earlier intervention. Despite this recognition, the survey highlighted that there is limited use today due to the perceived lack of clinical accuracy and utility data, high out-of-pocket patient costs, and lack of payer coverage. Conclusions: To overcome the hurdles for future widespread adoption of blood-based MCED tests, increased investment in data generation, education, and implementation of logistical support for HCPs will be critical. Initiatives include collaborations between stakeholders to generate near-term clinical utility data, equipping HCPs with the ability to educate patients on test accuracy, and seamlessly integrating the testing process into the patient visit workflow. The findings of this study can help build understanding of the anticipated barriers and inform strategies to alleviate them and build a foundation for clinical adoption of blood-based MCED tests.
Use of a deep learning model on H&E slides to predict nucleic acid yield for NGS testing.
Authors: Och Josh , Muller Yoni , Nagpal Kunal , Osinski Boleslaw , Hong Sun Hae , Stumpe Martin C. , Beaubier Nike , Jones Ryan D
Published: May 2024

e13589

Background: Samples sent for NGS may fail testing, leading to treatment delays or missed opportunities to offer patients targeted therapies. A common reason for assay failure is insufficient total nucleic acid (TNA). We developed and validated a model based on a digitized H&E slide and readily available clinical data that predicts whether samples will yield sufficient TNA for NGS testing. This model could lead to faster turnaround times and lower failure rates by helping choose patient blocks most likely to complete sequencing, or routing likely-to-fail samples to specialized extraction methods or smaller panel assays with lower input TNA requirements. We also evaluated the model’s ability to identify samples that yield abundant TNA, which could help pathologists spare tissue for other testing. Methods: We developed our model on samples received for NGS testing from January 1 - June 30, 2023, and tested on a large, real-world cohort of 9,707 samples received from July 1 - September 30, 2023. Cell count, assessed by a previously developed deep learning model on digitized H&E slides, along with the number of slides scraped, sample age, procedure type, and tissue site were used as model inputs. We measured the model’s ability to predict whether a sample yielded less than 100 ng of TNA (the target mass for the NGS assay used) and whether it failed sequencing. We also evaluated the model’s ability to predict whether a sample would have abundant TNA (defined here as yielding more than 1000 ng of TNA, 10x the target mass for the assay). Results: On the validation set, the model predicted samples that yielded TNA < 100 ng with a specificity of 98%, sensitivity of 26% and PPV of 82% (prevalence = 24%). It predicted samples that failed DNA sequencing with a specificity of 96%, sensitivity of 30% and PPV of 58% (prevalence = 15%); and samples that failed either DNA or RNA sequencing with a specificity of 98%, sensitivity of 23%, and PPV of 80% (prevalence = 27%). On the validation set, 742 samples were flagged, 430 of which failed DNA sequencing, and 590 of which failed either DNA or RNA sequencing. When predicting abundant TNA, the model predicted samples yielding TNA > 1000 ng at a specificity of 97%, sensitivity of 54% and PPV of 88% (prevalence = 26%). On the validation set, the model predicted 1544 samples as abundant, only 185 of which yielded TNA < 1000 ng and only 16 with TNA < 100 ng. Conclusions: The developed model holds promise as a tool for use at the beginning of NGS assays. It can be utilized to optimize testing decisions including selection of which samples to sequence, routing likely-to-fail samples to alternate testing methods, and sparing tissue for future assays from samples with abundant tissue.
Utility of liquid biopsy for predicting cancer type and informing treatment of carcinoma with unknown primary.
Authors: Bao Hua , Tang Haimeng , Chen Xiaoxi , Wu Xuxiaochen , Zhu Dongqin , Chang Shuang , Wu Xue , Shao Yang
Published: May 2024

e13606

Background: The advent of next-generation sequencing has greatly facilitated physicians in recommending tailored treatments for cancer patients. Despite these advancements, the dependence on the primary tumor site remains crucial for accurate diagnoses, posing a substantial obstacle in cases of carcinomas of unknown primary (CUPs) and hindering optimal patient care. To address this challenge, we propose the implementation of a machine learning model capable of identifying the tissue of origin (TOO) across 16 cancer types. Current standards gravitate to the use of tumor tissue for identifying primary tumor site. Leveraging the advantages of cell-free DNA (cfDNA), our approach provides a non-invasive and highly sensitive alternative to traditional biopsy or radiography methods. Methods: Cell-free DNA was extracted from patients diagnosed with carcinoma of known origin. The model underwent training using a dataset comprising 2,793 cfDNA samples, while the validation set consisted of 1,863 samples. The training and validation cohorts exhibited comparable demographics in terms of sex, age, and cancer types. Employing low-coverage whole genome sequencing (WGS), samples were analyzed to capture cfDNA features, including DNA fragment size distribution, copy number variation, nucleosome coverage pattern, mutational signature, and hotspot regions associated with cancer-related mutations. The final prediction model's accuracy was evaluated based on top 1 and top 2 predictions in accordance with the true tumor site of origin. Results: Overall accuracy of TOO predictions in the training cohort is 80.20% (2240/2793) for top 1 site and 90.26% (2521/2793) for top 2 sites. Overall accuracy of TOO predictions in the validation cohort is 81.80% (1524/1863) for top 1 site and 90.07% (1678/1863) for top 2 sites. Accuracy of tumor site prediction in the validation cohort is highest for lung cancer (Top 1 = 95.9%; Top 2 = 98.0%) tumor sites and lowest for biliary system and kidney tumor types (Top 1 = 54.3% & 57.4%; Top 2 = 71.6% & 63.2%). In the clinical setting, TOO estimation of 12/16 patients with CUP were identified to be in concordance with majority pathological consensus. Of note, two patients with CUP were diagnosed as lung cancer patients through TOO estimation. Molecular biomarkers of lung adenocarcinoma were also identified through targeted sequencing which corroborated the diagnosis, and chemoradiotherapy was recommended to the patient. Conclusions: We developed an accurate predictor of TOO by leveraging machine learning algorithm and incorporating cfDNA mutational, fragmentomic, and epigenetic features. Our results demonstrate high concordance between model-predicted and actual tumor sites across all examined cancer types. This model shows promise in offering valuable insights for the identification of cancers with an unknown primary origin using non-invasive cell free DNA samples.
Quantifying clinical actionability of updated tumor profiling reports through electronic health record (EHR)-enabled, on-demand ordering and resulting.
Authors: Huelsman Karen M. , Maher James F. , Parchman Andrew J. , Jones Ryan D , Posteraro Leo , Chen James Lin
Published: May 2024

e13621

Background: Next-generation sequencing reports provide matched therapies and clinical trials based on genomic alterations to drive therapeutic decisions in clinical practice. Biomarker-matched oncology drug approvals and trials have grown tremendously over the past decade. From January 2000 to October 2022 alone, a total of 573 agents were approved for various oncology indications, with nearly half being targeted therapies. While matched therapies and clinical trials are current at time of issue, updated variant classification, changes in FDA approvals, and trials available are not reflected in static reports. It is not always practical nor feasible to provide a new biopsy specimen. To address this gap in clinical care, we piloted Tempus Refresh, an on-demand informatics service that provides clinicians with refreshed therapy and trial matches from prior molecular reports directly through the EHR. Here we quantify the clinical actionability of Refresh reports. Methods: TriHealth piloted the Tempus Refresh orderable through the Epic EHR at the treating physician’s discretion. The clinical team specified prior DNA molecular reports (tissue or blood) to update. Orders were transmitted to Tempus through an HL7 interface. All alterations provided on the prior report were updated for therapeutic and trial matches through existing workflows. An updated structured report was then delivered to the TriHealth Epic EHR linked in the lab tab. Results: From 2/2023 to 11/2023, 10 TriHealth providers participated. A total of 35 unique Refresh orders were placed via custom HL7 Epic order, of which 3 were canceled due to orders outside of pilot parameters. Of the 32 Refresh reports, 34% (11/32) contained new FDA-approved therapies (OncoKB Level 1 or 2), and 78% (25/32) were annotated with new clinical trials. The average elapsed time from original date of report issuance to Refresh order delivery was 14.5 months (range 1 month to 45 months). The mean turnaround time for issuance of a Refresh report was 29 hours (range 5 hours to 53 hours). Conclusions: These results demonstrate that on-demand report updates increase the availability of tumor biomarker-matched therapies and trials. Furthermore, the study exhibits the feasibility of integrating updates directly into the standard EHR clinical workflow. This service provides visibility across teams and can support specialty pharmacists in therapy authorization. Considering the success of this pilot, future studies will assess the expansion of Tempus Refresh to additional sites.
On improving clinical trial diversity: Viewpoints from underrepresented breast cancer survivors.
Authors: Lee Kimberley T , Blackwell Rebecca M. , Maconi Melinda Leigh , Geiss Carley , Vadaparampil Susan Thomas , Gonzalez Brian D. , Jim Heather S.L. , Gwede Clement K , Soliman Hatem Hussein
Published: May 2024

e13674

Background: Racial and ethnic diversity in cancer clinical trials remains low. In this formative work, we sought to better characterize patient attitudes towards clinical trial participation. The goal is to build a framework that can be leveraged to develop an intervention to increase enrollment of participants from racial and ethnic minority groups in clinical trials. Methods: Semi-structured interviews were conducted with 10 Black and 10 Hispanic breast cancer survivors receiving care at a comprehensive cancer center in the South. Interviews were recorded, transcribed verbatim, and coded using thematic analysis. Results: Patient attitudes to clinical trials were generally positive. Many felt that trials were beneficial and a necessary part of advancing medical science. However, many expressed hesitations with regards to trial participation due to safety and efficacy concerns and distrust regarding motivation of healthcare system. Facilitators of positive attitudes towards clinical trials included positive social circles including family and community, as well as altruism regarding supporting racial and ethnic diversity in clinical trials. Conclusions: Collectively, these findings underscore the importance of implementing strategies to foster diversity in the biomedical research community, community outreach, and lay education, to improve trust in the system and therefore attitudes towards clinical trial participation in minority populations. [Table: see text]
UK Cancer and Transition Service (UCATS): Providing tailored cancer care to the gender-diverse community.
Authors: Berner Alison May , O'Callaghan Stewart , Lander Frances , Bower Mark
Published: May 2024

e13676

Background: Gender-diverse individuals identify their gender as different to the sex they were assigned at birth. This population experiences health inequity throughout the cancer care pathway partly stemming from limited access to specialist knowledge of gender-affirming care and its intersections with cancer. Notable issues include safety of gender affirming hormones, mutual implications of gender affirming surgeries with cancer surgeries and radiotherapy, and psychological support when dysphoria is exacerbated by a cancer diagnosis. Methods: In response, we established the UK Cancer and Transition Service (UCATS), a national virtual monthly multidisciplinary meeting (MDM) and clinic. Patients are eligible for referral if they identify as gender-diverse and have active or historical malignancy. The service was coproduced with patient and public involvement, including input from a specialist cancer charity for gender and sexual minority people. The service launched in June 2022 and began advertising and requesting patient feedback from January 2023. Results: Between June 2023 and January 2024 UCATS received 20 referrals (10 from gender services, 5 from oncology, and 5 self-referrals). Patients were aged 18 - 68 years. The most common tumour types were breast (n = 6), prostate (n = 5), and gastrointestinal (n = 3). Others were haematological, testicular, gynaecological, and central nervous system. One patient had a familial cancer syndrome, not active cancer. Patients were offered a virtual clinic appointment and MDM discussion. Reasons for referral included safety of gender affirming hormones and surgeries, and expedited gender consultations in view of prognosis, or need for cancer treatments that may affect gender-affirming care. Two patients did not attend, with one sending a nominated family member. Six patients had at least one external clinician dial in for the appointment. Seven patients received follow-up appointments. There were nine completed feedback forms, 4 after first appointment and 5 after follow-up. All patients rated both the communication at the appointment and the information given as 5/5. All patients rated their likelihood to recommend the service as 4 or 5/5. Other points of positive feedback were the detailed outcome letter, speed of appointment, and a sense of advocacy. Next steps include routine follow-up appointments (in response to feedback), wider advertising, increased frequency, and recruitment of nursing support. Conclusions: UCATS successfully caters to an unmet need, coordinating cancer and gender affirming care for gender diverse patients, and providing specialist knowledge and support for patients and care teams.
Racial disparities in breast cancer care among reproductive-aged women continued after COVID-19 pandemic.
Authors: Periyanayagam Usha , Yung Ethan , Kim Christine , Popadic Lyuba , Devine Francesca
Published: May 2024

e13757

Background: Despite the aggressive nature of breast cancer (BC) among women under 45 years old, racial disparities in BC care still exist. The COVID-19 pandemic highlighted racial disparities in care management. This study described staging, treatment use, and healthcare resource use (BC-HCRU) among reproductive-aged White, Asian, and Black women before and after COVID-19 to identify possible care changes. Methods: This retrospective claims study assessed White, Asian, and Black women aged 18 to 44 years old with newly diagnosed BC in the Komodo Research Dataset from August 2018-May 2023. Women were stratified based on their first observable BC diagnosis (index) into two cohorts, pre-COVID-19 (pre) (February-July 2019) and post-COVID-19 (post) (July-November 2022). Patients were required to have >6 months of medical and pharmacy continuous enrollment before (baseline) and after index (follow-up), and a second BC diagnosis during follow-up. BC-HCRU was defined as a claim with a BC diagnosis. Results: Pre-COVID-19 included 875 White, 116 Asian, and 267 Black women (mean age 39.0 years, 38.5 years and 37.8 years respectively) and post-COVID-19 included 879 White, 127 Asian, 386 Black women (mean age 38.8 years, 38.9 years and 37.9 years respectively). While the proportions with commercial insurance decreased (pre: White, Asian, Black: 72.5%, 71.6%, 42.7%; post: 51.9%, 61.4%, 23.6%) and with Medicaid increased (pre: White, Asian, Black: 24.3%, 27.6%, 53.6%; post: 45.2%, 38.6%, 75.1%) for all, most White and Asian women had commercial insurance and most Black women had Medicaid pre- and post-COVID-19. The proportion with metastatic BC increased for all in the post period, but lower incidences remained among White (pre: 20.7%; post: 25.1%) and Asian (pre: 17.2%; post: 22.8%) than Black women (pre: 25.5%; post: 28.0%). While both the proportions of White and Asian women with BC-related ER visits increased, suggesting greater acute care needs, the proportion of Asian women doubled and became higher than White women; the highest incidence also remained among Black women (pre: White, Asian, Black: 13.1%, 7.8%, 22.8%; post: 15.4%, 18.1%, 21.0%). The proportion with any treatment (medication, surgery, radiation) remained highest for Asian women (pre: 87.9%; post: 90.6%) and decreasingly lowest for Black women (pre: 84.3%; post: 80.3%), and the mean time to treatment remained shortest for White women (pre: 40.3 days; post: 44.3) and longest for Black women (pre: 47.4; post: 49.8). Conclusions: While COVID-19 affected BC care among all reproductive-aged women, racial disparities in BC care remained or increased in this vulnerable population. Comparative analyses assessing the factors driving these disparities should be explored to understand these health inequities further, and real-world clinical practice should consider these differences when implementing necessary BC management.
Evaluation of a self-reported G8 screening tool on Epic MyChart for older patients with cancer.
Authors: Wen Kuang-Yi , Swartz Kristine , Zhan Tingting , MacKenzie Amy R. , Chapman Andrew E.
Published: May 2024

e13766

Background: The Geriatric 8 (G8) is a screening tool validated for cancer patients to identify those in need of a comprehensive geriatric assessment (CGA). It evaluates eight domains encompassing mobility, polypharmacy, age, and self-rated health. The existing original-G8 requires administration by a healthcare professional, limiting its accessibility and practicality. An electronic, patient-reported version could broaden its reach, enhancing care coordination. This study focuses on the implementation and evaluation of a self-reported G8 tool on Epic MyChart and its alignment with the original-G8. Methods: The MyChart-G8 underwent adaptation from the original-G8, retaining all domains while optimizing questions for patient self-completion and adhering to health communication design principles. We introduced MyChart-G8 across our Jefferson health system for all patients aged ≥ 65 with a new cancer diagnosis. For a subset of patients, an oncology nurse or medical assistant also administered the original G8 during the new patient visit rooming process. Agreement between MyChart-G8 and original-G8 for individual items was measured using Kappa statistics. Diagnostic accuracy of MyChart-G8 compared to the original-G8 was also assessed. Results: Our cohort comprised 203 older cancer patients who completed both MyChart-G8 and the original-G8. The frequency of abnormal scores (≤14) for the original-G8 and MyChart-G8 was 40.0% and 67.7%, respectively. Discrepancies between the two tools were partly attributed to less than moderate agreement for three individual items: neuropsychological problems (Kappa 0.15), BMI (Kappa 0.27), and self-rated health (Kappa 0.31). A MyChart-G8 cutoff of 14.5 demonstrated the best balance of sensitivity (0.86 ± 0.13) and specificity (0.57 ± 0.06) when compared to the original G8. Conclusions: The incorporation of self-reported G8 assessments into Epic MyChart is feasible and implementable. Persistent challenges arise in accurately assessing self-reported problems among older adult cancer patients in the electronic format, potentially resulting in MyChart over-flagging abnormalities. The introduction of the Practical Geriatric Assessment (PGA) presents an opportunity to streamline the CGA. By subsequently conducting a PGA for individuals identified as vulnerable through the MyChart G8, we can confirm frailty domains, inform treatment decisions, and address impairments through targeted interventions. This integrated, stepped-up assessment approach holds significant potential to optimize resource utilization, enhance patient engagement, and tailor individualized treatments, ultimately with the goal of maximizing treatment outcomes. The Sidney Kimmel Cancer Center is in the process of developing a decentralized model of PGA using MyChart G8 as a step-up approach across the Jefferson Health enterprise.
Paramedical staffs' perception of their role during the continuum of care from detection to treatment in nursing homes: Results of the ONCOPAD-Pre survey.
Authors: Falandry Claire , Tavernon Charlène , Bret Judith , Simeone Arnaud
Published: May 2024

e13768

Background: Prevalence of cancer in nursing homes (NH) increases. ONCOPAD is a 4-step program dedicated to identifying and acting on educational needs, cultural and ethical barriers associated with cancer treatment in NH. The program included a scoping review (step 1), semi-directive interviews with care providers (step 2) designed to identify the major topics to be included in a tailored intervention and evaluated before and after it. Here we report the results of the survey before the intervention. Methods: Questions were mainly presented as 7-point Likert scales and classified into 6 sections: interviewee’s description, detection phase, treatment phase, relations and communication at work, ethical questioning, continuing education. Statistical analyses included descriptive statistics, exploratory factorial analyses, testing of model sphericity and sampling adequation. Results: From 06/2022 to 03/2023, 65 participants (median age 41 years; females: 84.6%) completed the questionnaire; 40.0% were nurses, 35.4% nurse assistants; 87.7% were full-time employees, and 73.8% were post holder. Interviewees considered their role as important at the detection stage (mean 4.82), to inform the physician (5.58) and their colleagues (5.45), their role during the decisional process (4.40) and to inform the patient on his diagnosis (4.05) were perceived as less important; organizational problems (lack of staff, time, facilities) could impede this stage. Factors perceived important for treatment decision were related to the patient (physical performance, cognition, age), his opinion (4.49), the opinion of his family (4.38), of his physician (5.17) and less to the paramedical team (4.02). The decision to pursue was mainly focused on care: pain relief (5.48), detection of clinical and psychological signs (5.18); the organizational barriers were perceived as major as well. Relations and communication at work, both internal and external to the institutions, were perceived as poor quality; 8 (12.3%) of the interviewees even skipped this section. The ethical questioning was permanent and homogeneous. Considering education, the interviewees felt insufficiently trained and the preferred model for training was short sequences integrated into daily work schedules; coordinating physicians appear as good mediators for such training courses. Conclusions: In this survey, paramedical staffs perceived their role as important during both detection and treatment of cancers, focusing more on care than cure; however, organizational constraints and poor quality of internal and external relations, and communication appear as major barriers in the completion of their role. Educational intervention should be tailored, favoring short sequences integrated into daily work schedules, coordinating physicians appear as good mediators for improvement in the future.