bluuebunny/crossref_metadata_2025 huggingface dataset:
Association of circulating T lymphocytes and their functional states with pathologic complete response (pCR) in breast cancer (BC). A prospective Italian study.
Authors: Ben Ayed Rahma , Conte Benedetta , Martini Veronica , Boldorini Renzo , Gobbato Simone , Ruffilli Beatrice , Vezzoli Francesca , Alsati Rami , Negrini Letizia , Sala Nicole , Matera Letizia , Branni Carmen , Dodaro Ivan , Gambaro Anna , Rossi Valentina , D'Avanzo Francesca , Gennari Alessandra
Published: May 2024

559

Background: In BC, pCR is associated with substantial survival benefit. Hence, escalated neoadjuvant treatments (NATs) are being increasingly employed to improve pCR rates, warranting biomarkers for better patients’ selection. T-cell exhaustion and senescence are dysfunctional states that coexist in patients with cancer, impairing antitumor immunity and sustaining a suppressive immune microenvironment. Here, we assessed the impact of such states on pCR across different BC subtypes and NATs. Methods: This is a prospective study on patients undergoing NAT for BC at the Maggiore Hospital of Novara, Italy. Blood was collected at baseline and after NAT. Circulating T lymphocytes were characterized with exhausted (CD28, PD1, LAG3) and senescent (CD57, KLRG-1) biomarkers utilizing flow cytometry. Neutrophiles/lymphocytes ratio (NLR) and lymphocytes/monocytes ratio (LMR) were also retrieved. Subpopulations with frequency <1% were normalized for total CD3+ cells. Results: From October 2020 to January 2024, 134 patients were enrolled and 115 completed NAT (85.8%). Fifty-one (38,1%) had adequate samples for analysis, 16 (31,4%) with hormone receptor positive HER2 negative BC (HR+HER2-), 15 (29,4%) with HER2+, and 20 (39,2%) with triple negative BC (TN). At baseline, patients with TNBC had the lowest NLR (p=0.018) and lowest senescent CD4+CD28- (p=0.042). Associations with pCR are shown in the Table. Overall, LMR associated with increased pCR (OR 1.34 [95% CIs 1.00-1.89]), and NLR with decreased pCR (OR 0.67 [0.39-1.04]). Both associations were driven by HR+ status (interaction p = 0.061 and 0.060). Senescent CD4+ predicted lower pCR in both HR-HER2+ (OR 0.10 [0.01-0.36]) and TNBC (OR 0.10 [0.01-0.5]). In TNBC, exhausted CD8+ predicted higher pCR (OR 1.78 [1.08-3.79]). When assessed separately in patients who received NAT with or without pembrolizumab, exhausted CD8+ remained predictor of pCR in chemotherapy + pembrolizumab (OR 1.84 [1.03-5.00]), but not with chemotherapy alone (p=0.203). The dynamics of paired pre-NAT and post-NAT TNBC samples revealed significant differences. Senescent CD4+ increased after chemotherapy, but not with chemotherapy + pembrolizumab (p=0.007). Pembrolizumab was associated with depletion of PD1-positive CD8+, while chemotherapy alone was not (p=0.020). Conclusions: The characterization of circulating T lymphocytes could help identify patients who benefit more in terms of pCR from specific NATs, including chemoimmunotherapy. [Table: see text]
The landscape of the intestinal microbiome amongst patients with newly diagnosed invasive breast cancer (BC) and ductal carcinoma in situ (DCIS).
Authors: Sammons Sarah L , Kuntz Thomas , Hughes Melissa E. , Morgan Xochitl , Waks Adrienne Gropper , Garrido-Castro Ana Christina , DiLullo Molly , Ligibel Jennifer A. , Ogayo Esther R. , Giordano Julia , Ryan Sean , Rahman Tasnim , BARROSO-SOUSA ROMUALDO , Martin Alyssa R. , O'Quinn Casey , Parker Tonia , Lin Nancy U. , Mittendorf Elizabeth A. , Tolaney Sara M.
Published: May 2024

563

Background: The gut microbiota has been recognized as a master modulator of the immune system and has been associated with outcomes among cancer patients. There is a paucity of knowledge surrounding the landscape of the gut microbiome in BC pts with invasive and non-invasive disease or how it can affect response to systemic therapy. We sought to define the landscape of the gut microbiome in invasive BC and DCIS patients and evaluate differences by subtype. Methods: Prospective clinical trials (NCT04425018 and NCT02752685) and institutional registries enrolling patients with DCIS and stage I-III invasive BC at a single institution collected baseline stool samples prior to initiation to systemic therapy. Samples underwent whole-genome metagenomic sequencing (2 x 150 bp, Illumina NovaSeq) and data were processed into taxonomic (species) abundances using MetaPhlAn4. Associations between metadata and ecological features (alpha and beta diversity) were tested with ANOVA and PERMANOVA. Individual species were tested for association as univariable linear models on normalized, log-transformed relative abundances, with p-values FDR adjusted for multiple comparisons, using MaAsLin2. Results: 278 baseline samples were analyzed: 43 DCIS, 101 TNBC, 54 HR+/HER2-, 24 HR-/ HER2+, 37 HR+/HER2+. Most patients were age >50 (71%) and white (83%). No significant differences were observed in baseline stool microbiomes between invasive BC and DCIS pts for alpha (p = 0.185) or beta (p= 0.476) diversity, nor for individual microbial species. HR+/HER2+ BC had a unique microbiome profile with significantly different beta diversity (p = 0.005), with six associated species (q < 0.25). No other associations with invasive BC subtype were observed. Bacteroides ovatusabundance was significantly different between Stage I and III BC pts (p = 0.0003, q = 0.116). Several taxa were associated with age at diagnosis. Conclusions: No significant differences were observed in baseline stool microbiome composition between patients with invasive breast cancer and DCIS. HR+/HER2+ BC microbiome composition was distinct from other subtypes, and a significant difference in Bacteroides ovatus abundance emerged between Stage I and III pts, suggesting potential microbial associations with cancer subtypes and progression.
Combination of predicted sensitivity to endocrine therapy (SET2,3 index) and the Recurrence Score in node-positive breast cancer: Independent validation in the PACS-01 trial.
Authors: Penault-Llorca Frederique Madeleine , Lusque Amelie , Filleron Thomas , Tran Kevin , Du Lili , Baehner Frederick , Dalenc Florence , Lacroix-Triki Magali , Bachelot Thomas , Andre Fabrice , Boucher Pascal , Lemonnier Jerome , Symmans W. Fraser Fraser
Published: May 2024

565

Background: SET2,3 index measures hormone receptor-related transcriptional activity (SETER/PR) adjusted for a baseline prognosis index (BPI) derived from tumor size, nodes involved and a 4-gene molecular subtype (RNA4). SET2,3 added prognostic information to the 21-gene Breast Recurrence Score (RS) in the SWOG 8814 trial (1). To confirm this, we independently evaluated both tests performed on node-positive, hormone receptor-positive (HR+) cancers from the PACS-01 trial (Roche et al, JCO 2006, PMID: 17116941) that evaluated the addition of adjuvant docetaxel to anthracycline-based chemotherapy. Adjuvant endocrine therapy became standard for premenopausal patients during PACS-01, justifying a sensitivity analysis in the population who received adjuvant endocrine therapy. Methods: SET2,3 was measured with the QuantiGene Plex bead-based hybridization assay (ThermoFisher) using an aliquot of residual RNA from prior RS testing in 791 HR+ tumor samples. Pre-defined cut points defined higher risk if RS >25 or SET2,3 <2.10. SETER/PR index and BPI, individual components of SET2,3 index, were evaluated as continuous variables. The primary endpoint was distant recurrence-free interval (DRFI). Multivariable Cox proportional hazards models were used to calculate hazard ratios with 95% confidence interval (HR, 95%CI) adjusted for treatment arm, and the likelihood ratio (LR) of benefit from addition of SET2,3 to RS with LR test for significance at p <0.05. Results: Of 791 tumor samples, 760 (96.1%) passed quality control (QC) for the SET assay; 724 had pathologic information to calculate SET2,3 index; and 659 had results for RS and SET2,3. At a median follow-up of 8 years, distant recurrence occurred in 144 of 659 (21.9%) patients overall, and 94 of 490 (19.2%) patients in the sensitivity population. Overall, high RS status (HR 2.33, 1.60-3.39) and high SET2,3 (HR 0.43, 0.30-0.62) were independently prognostic. SET2,3 was high in 303/377 (80.4%) patients with RS ≤25, with 5-year DRFI of 93.7% [95%CI 90.2;95.9]; and SET2,3 was low in 171/282 (60.6%) patients with RS >25, with 5-year DRFI 64.6% [95%CI 56.9;71.3]. SETER/PR index of endocrine transcriptional activity and the BPI, each contributed additional prognostic information to RS status in the sensitivity population (Table). Conclusions: SET2,3 index added prognostic information to the Recurrence Score in this independent blinded validation study of the PACS-01 trial for node-positive breast cancer. 1. Speers et al, JCO 2023, PMID: 36649570. [Table: see text]
Clinical application of novel mobile AI solution for real-time detection and differential diagnosis in breast ultrasound: The first prospective feasibility study.
Authors: Lee Jeeyeon , Cheng Tsui-Fen Fiona
Published: May 2024

574

Background: Existing artificial intelligence (AI) solutions for breast ultrasound faced limitations due to their non-real-time detection and server dependency. However, novel mobile real-time AI solution now enable on-device detection and differential diagnosis, aiding in immediate decision-making. This study aims to evaluate the feasibility and effectiveness of such a mobile AI solution in clinical settings, by comparing it against expert breast imaging diagnoses. Methods: From August to December 2023, a feasibility study was conducted in tertiary medical center of Taiwan using mobile AI solution (CadAI-B for breast, BeamWorks Inc., Korea). CadAI-B is connected via HDMI or DVI to an ultrasound equipment using tablet PC. It supports healthcare providers to detect suspicious breast lesions by highlighting suspicious area during breast ultrasound scanning, and to make a differential diagnosis by providing BI-RADS categories and malignancy score (0-100%). The rate of real-time detection in malignancies and area under the receiver operating characteristic curve (AUC) was calculated. Distribution of BI-RADS categorized by CadAI-B were compared with those by breast imaging experts on independent review. Results: The analysis included 33 patients with an average age of 47 years (IQR, 44 – 62). There were 14 malignancies, 17 benign lesions, and 2 normal cases, and 30 patients (90.9%) underwent biopsy. For patients with malignancies, CadAI-B successfully identified all malignancies. Overall diagnostic performance, as AUCs calculated by the malignancy score and BI-RADS, was 0.835 and 0.850, respectively. The per-patient sensitivity of CadAI-B was 100.0%, while the specificity was 52.6%. The BI-RADS distribution between CadAI-B and expert was the same in malignant cases. In benign cases, CadAI-B categorized 9 cases (50.0%) as C4A or C4B, while experts classified 13 cases (72.2%), indicating a potential reduction in the need for biopsy. Conclusions: This study demonstrates that real-time processing capabilities of CadAI-B enable the identification of critical lesions during breast ultrasound, helping to reduce unnecessary biopsy. These findings may be helpful in diagnostic decisions and training of non-experts in clinical settings and offer the potential to improve workflow efficiency. [Table: see text]
Radiofrequency ablation without excision for breast cancer: 5-year results of ipsilateral breast tumor recurrence-free survival in the RAFAELO study (NCCH1409).
Authors: Kinoshita Takayuki , Takayama Shin , Takahashi Masato , Fujisawa Tomomi , Yamamoto Naohito , Shien Tadahiko , Futamura Manabu , Ito Mitsuya , Takahashi Mina , Aogi Kenjiro , Watanabe Kenichi , Onishi Tatsuya , Yoshida Masayuki , Tsuda Hitoshi , Shibata Taro , Yorikane EIko , Ohata Keiko
Published: May 2024

578

Background: The RAFAELO study is designed to evaluate the safety and efficacy of breast radiofrequency ablation, enabling women between 20 and 79 years of age with small breast cancers to benefit from a nonsurgical treatment and to avoid the associated surgical risks. Methods: The RAFAELO study is a prospective, multi-center, single-arm, confirmatory trial including women between 20 and 79 years of age with unifocal, MRI and ultrasound-visible invasive ductal carcinoma or ductal carcinoma in situ size 1.5 cm or smaller diagnosed by preoperative core-needle biopsy, and classified as any grade, any hormone receptor (HR) status, and any human epidermal growth factor receptor 2 (HER2) status. The primary endpoint was Ipsilateral breast tumor recurrence (IBTR) -free survival at 5 years. e planned sample size was set at 372 considering patients lost to follow-up to achieve the power of 80% with the one-sided alpha of 5%, the expected 5-year IBTR-free survival of 93.7%, and the threshold of 90%. The IBTR-free survival time was estimated using the Kaplan-Meier method. Results: Between August 2013 and November 2017, 372 patients were enrolled in this study. A total of 370 patients received successful radiofrequency ablation per protocol and 353 patients were included for the efficacy analysis. The median age was 55 years (range, 32-78 years). With median follow-up period of 5 years, IBTR was observed in 2 patients among 353 patients. The 5-year IBTR-free survival was 98.6% (90% CI 97.1%-99.3%) and the primary endpoint was met as its lower limit of 90% CI exceeded the threshold (90%). As device-related adverse events during radiofrequency ablation, burns were observed in 4 (1.1%) for Grade 1 and 3 (0.8%) for Grade 2 among 370 patients. No severe device-related adverse events were reported. Conclusions: Breast radiofrequency ablation presents a promising alternative to surgery while offering the benefits of a minimally invasive procedure with minimal risks. Breast cancer patients in Japan can now avail themselves of this minimally invasive treatment that’s subsidized by public insurance. Further analysis within this clinical trial or registry is needed to confirm radiofrequency ablation as a viable alternative to surgical excision for breast cancer patients in the point of cosmetic results and patient’s satisfaction. Clinical trial information: jRCTs032180229 .
Automated digital oncologic data review for breast cancer research: AI-enabled mCODE and field-of-interest extraction framework.
Authors: Choi JI-Woo , Park Seho , Sohn Joohyuk , Lew Dae Hyun , Sung Sihyun , Choi Ye-Lim , Lee Sarang , Yang Eun-Jung
Published: May 2024

e12647

Background: Enhancing outcomes in cancer care and research can be optimally achieved by accelerating data extraction from unstructured electronic health resources. Understanding the association between treatment response markers and long-term outcomes is crucial for refining cancer therapeutic approaches and improving patient prognosis. In this study, we explore the association of oncologic outcomes with pathologic complete response (pCR) in high-risk early-stage breast cancer treated with neoadjuvant chemotherapy (NACT) using automated oncologic data extraction framework. Methods: Patients with primary stage I-III breast cancer who received NACT followed by mastectomy, with or without immediate breast reconstruction from January 2010 to August 2023 were retrospectively analyzed. We extracted pCR results and data on clinical and pathological stage, tumor subtype, grade, and treatment regimens and factors affecting postoperative complications from electronic medical records based on the AI enabled-mCODE (Minimal Common Oncology Data Elements) and fields of interest extraction framework. Employing mixed-effects Cox models, we explored the association between pCR and event-free survival (EFS), distant recurrence free Survival (DRFS) and overall survival (OS). Survival curves of patients were estimated using Kaplan-Meier method. Multivariate analysis was performed to evaluate the predictive factors for pCR. Results: Overall, 2725 patients were analyzed. The median age was 50.6 years. The median follow-up was 67 months. pCR was achieved in 31.0%. Hazard ratio for pCR vs. non-pCR were 0.34 for EFS (95% CI, 0.25-0.45), 0.32 for DRFS (95% CI, 0.23-0.43), 0.21 for OS (95% CI, 0.13-0.34), varying from 0.13 to 0.56 for EFS, 0.12 to 0.48 for DRFS and 0.07 to 0.40 for OS. The presence of pCR remained prognostic for event-free survival in multivariate models adjusted for age, tumor size, and nodal status at baseline. Conclusions: This study confirms that patients achieving pCR after NACT have better long-term survival outcomes that patients who do not. Oncologic data extraction from unstructured electronic medical records using AI-enabled extraction framework can be expected to enhance robust cancer research and generate valuable insights from real-world practice settings for tailored therapeutic decision-making. [Table: see text]
Predictors of response and surgical approach after neoadjuvant chemotherapy in receptor-positive/HER2-negative stage II-III breast cancer patients treated in two private cancer care centers in Lima, Peru: Real-world data.
Authors: Aldecoa-Bedoya Franklin , Aldecoa-Falcon Sebastian , Falcon Silvia Gabriela
Published: May 2024

e12659

Background: The role of neoadjuvant chemotherapy (NAC) in hormone receptor-positive HER2-negative breast cancer (BC) is controversial, its main benefit being to improve the surgical outcome in both breast and axilla. The aim of this study was to evaluate the response to NAC, as well as possible predictors and the type surgery performed after primary treatment. Methods: Observational, retrospective study from a database of 1356 consecutive cases of BC between 2016 and 2022 in two private oncology centers in Lima Metropolitana. There were 726 new cases of hormone receptor-positive HER2-negative BC (53.5%), of which those patients with clinical stage II-III who received NAC were considered (n=122, 16.8 % of luminal HER2-negative). Results: The average age of the sample was 46.6 years (range 25-72) with a predominance of luminal B subtype (60.7%) and clinical stage II disease (51.6%), as well as an average delay time to treatment of 33.9 days. Chemotherapy choice was AC every 3 weeks followed by weekly paclitaxel (98.4%). The pathological complete response (pCR) rate was of 16.4% in the breast, 29.1% in the lymph nodes and 13.9% in both. None of the variables studied (age, histologic grade and type, clinical stage, tumor size, number of nodes, hormone receptors, Ki-67 and HER2 low) were predictors of pCR. According to RECIST criteria, tumor shrinking in the breast occurred in the majority of patients (partial and complete response: 86.1%) and eight out of ten patients achieved a tumor size reduction of more than 50%. The rate of mastectomy was 67.2% and radical axillary dissection, 70.5%. Conclusions: In our cohort, we found a pCR rate similar to that reported in the world literature. No predictors of pCR were found. Despite the high proportion of tumor response at breast and node level, the surgical approach was mostly radical. The multidisciplinary BC committee in our setting should be strengthened in order to make better decisions on the surgical approach for patients with hormone receptor-positive HER2-negative stage II-III BC who receive NAC.
Results of neoadjuvant therapy for patients with triple negative breast cancer in a public hospital in Brazil (Federal District).
Authors: Amaral De Castro Rafael , Haum Fernanda das Neves Carneiro , Nunes Andrew Sá , Schorn Patricia Werlang
Published: May 2024

e12660

Background: Breast cancer is the neoplasm with the highest number of deaths among women in Brazil. Triple negative breast cancer contributes to the worsening of this condition, considering that it is more aggressive, accounting for 15% of deaths. Furthermore, more aggressive treatments and new medications have recently been added to neoadjuvant protocols, improving the complete pathological response, but with more side effects. In this way, it is predictive to understand the profile and treatment of choice for patients diagnosed with triple negative breast cancer, contributing to a better understanding of the treatment outcome, survival and quality of life in patients with this health condition. Methods: observational and cross-sectional study with retrospective data collection, in the electronic medical record of the TrakCare system. Patients diagnosed with triple-negative breast cancer between January 2020 and December 2021 and who underwent neoadjuvant treatment were included. Information was collected regarding the date of treatment, age, color/race, comorbidity, staging, type of chemotherapy used, postoperative response rate, and patient evolution during follow-up. Results: 78 patients with triple-negative breast cancer were included. The average age of patients was 56.3 years (26 – 83 years) and approximately 38.5% of patients were under 50 years of age. Around 42.3% of patients had hypertension and 33.3% were obese. Only 28.2% of patients did not have associated comorbidities. Approximately 59% of patients were staged T4 and 35.9% staged T3. Pathological complete response (cPR) was achieved in 56.4%, but progression was recorded in 13% of cases. In 88.5% of patients, the AC-T protocol was used (doxorubicin and cyclophosphamide followed by weekly paclitaxel) and 52% obtained CPR. On the other hand, only 11.5% (9 patients) used the AC-TC protocol (doxorubicin and cyclophosphamide followed by paclitaxel and carboplatin) with a CPR of 89% (p=0.016), with no record of progression or death. Conclusions: Triple negative patients were young and tended to have at least one comorbidity in addition to a highest rate of locally advanced tumor. The more aggressive protocol (AC-TC) was used less often, but has a higher rate of cRP and should be used more frequently in this scenario despite the greater complexity of these patients.
The transformative role of digital health platforms: Bridging diversity gaps in cancer care in younger patient populations.
Authors: Lapidot Yelena , Gaziel Avital , Bader Tzvia
Published: May 2024

e13503

Background: Digital health platforms are transforming cancer care by offering unprecedented access to treatment options, including clinical trials (CTs). In this study, we analyzed data from the Leal digital health platform to identify demographic and behavioral trends among patients that may have implications for quality care and access to advanced treatments. Methods: Leal is an AI-based platform that matches cancer patients to CTs based on a self-reported medical profile. The profile includes parameters essential for CT matching, including disease status, stage, biomarker/mutational status, treatment history, comorbidities and demographics. The analysis incorporated data from 34,913 Leal Health community members, spanning a range of cancer types and encompassing all disease stages. Results: The digital platform attracted a significantly younger user base, while also reflecting key demographic trends consistent with the broader real-world cancer patient population. Specifically, 45% of the users were under 60 years old, and 20% were under 50, leading to a mean age of 60 years. This is notably younger than the general cancer patient population's mean age at diagnosis of 66 years (p = 0.03). The platform engaged diverse demographics, particularly among younger age groups (p<0.0001). Notably, one-third of users under 40 and over a quarter under 60 belonged to minority groups. African American at younger ages represented about 10% of all signups, bridging a significant disparity for this minority group, even more so within the space of CT search and recruitment where African Americans represent up to 5% of patients. Moreover, younger users exhibited significantly higher disease knowledge (p<0.0001), enhancing their potential for precise matching with advanced treatments. Conclusions: Digital health platforms uniquely attract younger and more diverse demographics, reflecting a broader spectrum of patient needs and experiences while significantly bridging racial disparity in CTs representation. This shift has profound implications for healthcare knowledge and outcomes. Our findings highlight the importance of adopting digital platforms to address the unique needs of the younger patient population.
A retrospective machine learning–based analysis of nationwide cancer comprehensive genomic profiling data to identify features associated with recommendation of mutation-based therapy.
Authors: Ikushima Hiroaki , Watanabe Kousuke , Shinozaki-Ushiku Aya , Oda Katsutoshi , Kage Hidenori
Published: May 2024

e13510

Background: Comprehensive genomic profiling (CGP) has played key roles in cancer precision medicine through optimization of therapeutic interventions based on genomic alterations in cancer cells. However, the probability of discovering mutation-based treatments through CGP remains low. To enhance the effectiveness and efficiency of cancer precision medicine, it is crucial to identify patients who are likely to benefit from CGP tests. This study aims to identify characteristics of patients in which mutation-based treatments are discovered by CGP tests. Methods: We retrospectively analyzed data from 60,655 patients who underwent CGP tests and were registered in the Center for Cancer Genomics and Advanced Therapeutics (C-CAT), the national data center for cancer CGP in Japan. The C-CAT database covers 99.7% of cancer patients who have undergone CGP tests in Japan. Major cancer types included 10,182 cases of bowel cancer, 8,691 pancreas cancer, 5,062 biliary tract cancer, and 3,777 breast cancer. We developed an eXtreme Gradient Boosting (XGBoost) model using machine learning, and used clinical information as input to predict whether one or more Japanese Pharmaceuticals and Medical Devices Agency (PMDA)-approved drugs are discovered through CGP tests or not. Shapley Additive Explanations (SHAP) was employed to extract significant features that contribute to the model prediction. Results: The prediction model achieved an area under the receiver operating characteristic curve of 0.826 for the overall cancer population. Positive SHAP values were observed for patients with breast (mean SHAP in breast cancer patients: 1.38), lung (1.08), bowel (0.75), and pancreas cancers (0.35), while negative SHAP values were associated with head and neck (-1.75), cervical cancers (-1.54), and brain (-1.33). Positive SHAP values were also associated with presence of liver or lymph node metastasis (0.23, 0.08), shorter intervals between diagnosis and CGP testing or specimen collection and CGP testing, and advanced age. Similar trends were observed in cancer-type-specific prediction models, which also identified their own unique features. In the adolescent and young adult (AYA) age group, primary brain tumors were strongly associated with negative SHAP values (-1.37). Conclusions: Our machine learning-based analysis of nationwide CGP data identified features that predict cases in which mutation-based treatments are discovered by CGP tests, both in the overall cancer population and within specific cancer types and the AYA age group. Expedited CGP testing is recommended for patients who match the identified profile to facilitate early targeted therapy interventions.
Impact of a proactive patient assistance program for diverse ambulatory oncology patients: A retrospective cohort study.
Authors: Falconer Patricia P , Phillip Alexandra Elyse , Scott Aja M , Philipp Lisa
Published: May 2024

e13513

Background: Significant differences persist in cancer incidence, survival, morbidity, and mortality among populations in the U.S. Individuals of lower socioeconomic status (SES) suffer disproportionately from cancer and other disease burdens compared to individuals with higher SES. Financial hardship is increasingly common, with many cancer survivors reporting difficulty paying medical bills, high financial distress, and delaying or forgoing care because of cost. Cancer patients reporting financial hardship are more likely to have psychosocial distress. Financial distress has been linked with several clinically relevant patient outcomes including quality of life, symptom burden, compliance, and survival. An NCI-designated comprehensive cancer center (CCC) with a diverse racial, ethnic, and linguistic patient population utilizes My Wellness Check (MWC) program to identify patients experiencing emotional, physical, practical, and social concerns. Among 4,117 MWC patient responders representing 43.1% of eligible patients during October 2019 - February 2022, 801 patients (19.5%) with 976 supportive or practical needs alerts were triggered to social workers where only 68.4% of the alerts were acted upon within a 72-hour window. For patients identified by MWC as having financial toxicity, Social Workers identified available resources to assist with patients’ out-of-pocket costs. Methods: In July 2022, the CCC launched a patient financial assistance program which included screening of all patients receiving systemic therapy administered at infusion centers. A third-party partner was contracted to provide patient advocates and technology augmenting the EHR. Patient Advocates identified eligible patients and enrolled them into financial assistance programs. Results: A retrospective analysis was performed for the period of May 2022 - December 2023, comparing patients receiving philanthropic medical financial assistance consisting of copay assistance and grants sponsored by drug manufacturers and diagnosis based non-profit foundations with infusion center patient population demographic data. The cohort participating in patient assistance programs included a higher percentage of female, Hispanic, age 27-64, commercially insured, and patients that reside in high and medium-high Social Vulnerability Index (SVI) counties. Conclusions: A proactive patient financial assistance program can help reduce financial distress for patients with cancer, especially those residing in high and medium high SVI counties. Leveraging the expertise of a third party helps mitigate financial toxicity in the short term and can help drive more equitable cancer outcomes.
A simple and data-driven framework to foster multidisciplinary and timely care in resource-limited settings: A pilot program in Argentina.
Authors: Melendi Santiago Ezequiel , Tribiño Maria Laura , Feldman Carolina , Bianconi Maria Ines , Perez Virginia , Jankilevich Gustavo
Published: May 2024

e13517

Background: While numerous reports discuss various navigation methods and their effectiveness, implementing these programs in low- and middle-income countries (LMICs) is challenging. This study addresses this gap by assessing the feasibility of implementing a simple strategy using a small set of essential data gathered during routine patient care. The aim was to foster multidisciplinary case discussion and monitor key performance indicators (KPIs) to achieve timely access to treatment. Methods: As part of the BOLD initiative (Barriers or Limits Demolished Against Breast Cancer), we started a pilot program with the Breast Unit and the Medical Oncology Consult in the outpatient setting of a public hospital serving a vulnerable population in Buenos Aires City. Using a web-based spreadsheet accessible to both units, a simple framework collecting relevant consultation dates was implemented to assess the timeliness of specialist referrals and treatment initiation. We configured simple time-based alerts to highlight patients who exceeded prespecified timeframes, enabling healthcare providers to promptly reach out to patients, inquire about the reasons for access issues, and provide counseling to address them when possible. Results: The Breast Cancer Unit admitted 38 newly diagnosed patients from Sep/2023 to Nov/2023, of whom 22 (57.9%) had no health insurance. The main program KPIs are described in the Table. Surgery was the most frequent source of treatment delays (58.3%), mainly because of the scarce availability of operating rooms. Alerts from delayed initiation of systemic oncological treatments were present in 11 patients (28.9%). Navigation of those patients attributed the primary source of delays to administrative issues in the prior authorization process (45.5%, n=5), followed by patient-related factors such as social vulnerability and difficulty in coping with required procedures (n=4). Conclusions: A simple framework based on the prospective register of key consultation dates was feasible to implement in the routine care setting of a public hospital serving a vulnerable population. This model promotes quality and equity for breast cancer patients by providing an accessible way for LMICs to ensure a timely referral process, foster multidisciplinary case discussion, and offer patient support to overcome challenges arising primarily from delays within the health system. [Table: see text]
Barriers to accessing cancer care from patients’ perspective: A single cancer center experience.
Authors: Patel Dhaval , Rosenberg Marshall Isaac , Leighton John Charles , Dourado Claudia M.
Published: May 2024

e13520

Background: Jefferson Einstein Hospital is a safety-net hospital that serves a diverse and primarily disadvantaged community in North Philadelphia. The population in this city has 21.5% of individuals living in poverty, which is almost double the rate in Pennsylvania. According to the National Cancer Institute’s Center to Reduce Cancer Health Disparities (NCI-CRCHD), people from low socioeconomic backgrounds and specific demographics often bear a more significant disease burden than the general U.S. population. Certain population groups experience cancer disparities due to their likelihood of encountering obstacles or barriers in accessing healthcare. This study aims to identify critical barriers hindering the receipt of quality cancer care for the population served by this hospital. Methods: We identified 51 adult patients who received a new cancer diagnosis between 2022 and 2023. Barriers to accessing cancer care were defined through a literature review and expert consensus. These barriers were assessed via a survey containing fixed-choice items aimed at eliciting obstacles to accessing cancer care among newly diagnosed cancer patients undergoing treatment at the hospital. Information on these barriers was collected prospectively during survey administration and analyzed using descriptive statistics. The frequency of specific barriers within the five categories was calculated, and subjects were classified based on the presence or number of barriers. Results: A total of 51 patient surveys were evaluated. Among these surveys, 24 (47%) reported transportation issues, and 3 (6%) reported caregiving responsibilities. Ten (20%) patients encountered economic barriers, while 11 (22%) faced challenges related to their support system. Nineteen (37%) patients experienced barriers related to health literacy, and 15 (29%) specifically struggled with cancer-related health literacy. Additionally, cultural barriers were identified in 12 (24%) patients. Conclusions: Our study highlights the prevalent barriers faced by newly diagnosed cancer patients in accessing cancer care, including transportation, health literacy, financial constraints, and cultural factors. These findings underscore the importance of integrating patient perspectives into future initiatives aimed at addressing these challenges. By prioritizing patient input and enhancing patient navigation programs, we can effectively mitigate these barriers and improve access to cancer care for individuals in need. [Table: see text]
Incidence of germline genetic testing in Veterans with breast cancer in the Veterans Health Administration.
Authors: Halwani Ahmad Sami , Patil Vikas , Mcshinsky Richard , Morreall Deborah , Rasmussen Kelli M , Li Chunyang , Burningham Zachary R. , Menendez Carolyn S. , Chiba Akiko , Moss Haley , Colonna Sarah Violet , Rowe Kerry G. , Kelley Michael J.
Published: May 2024

e13531

Background: The Department of Veterans Affairs (VA) has seen a 3-fold increase in breast cancer (BC) diagnoses in recent decades, 90% of which occur in women Veterans. While technological and biomedical advances have increased the availability and actionability of germline genetic testing (GGT), adoption in practice has been slow. The VA National Oncology Program (NOP) recommends that all Veterans with BC be offered GGT. The Making Advances in Mammography and Medical Options for Veterans Act of 2022 mandated that the VA perform a study of GGT in Veterans with BC, the initial results of which are reported here. Methods: Veterans diagnosed with BC between Jan 1, 2021 and Dec 31, 2022 were identified in the VA Cancer Registry System (VACRS) using site code C50 and excluding histology codes 95903, 96803, and 96993. Of those, Veterans receiving care for BC in the VA were defined as those having at least 2 visits within a year with VA hematology, oncology, radiation oncology, or surgery with codes C50.x, D05.x, Z17.x, Z19.x, or Z85.x. We retrieved clinical notes from these visits and used natural language processing (named entity recognition, entity linking) to identify and highlight relevant concepts to expedite chart review. We randomly selected 200 Veterans, loading their notes into a custom-designed chart review application. A team of 5 clinical subject-matter experts reviewed these notes for evidence of GGT. Each Veteran’s notes were reviewed independently by 2 reviewers. Disagreements were adjudicated by the whole team. Results: 1505 Veterans met diagnostic criteria in VACRS; of these, 1201 met utilization criteria and constituted the study population. Table summarizes demographic characteristics. Inter-annotator agreement was 85.5%. Of the 200 Veterans whose charts were reviewed, 118 (59%) were offered testing, referred to a genetic counseling service, or otherwise had evidence of testing found upon chart review, while 61 (31%) had no such evidence. Ten patients (5%) were deemed ineligible for GGT based on practice guidelines at the time, and chart review found that 11 (6%) had no evidence of clinical care within the VA. Among 189 seen by a VA oncology clinician, 118 (62.4%) had or were offered genetic services. Conclusions: Most Veterans with breast cancer are offered germline genetic testing. Future work will evaluate ongoing efforts to improve adherence to VA NOP guidelines to ensure that every Veteran with breast cancer can access germline genetic testing. [Table: see text]
Expanding diversity in colorectal cancer studies with a focus on Hispanic and Latino participant enrollment.
Authors: Lateef Syed K , Chaudhary Kanza , Kutnik Karolina , Lu Yontao , Xu Chuanbo , Lee Lilian C. , Baldo Lance , Shaukat Aasma , Levin Theodore R.
Published: May 2024

e13532

Background: Colorectal cancer (CRC) is a leading cause of cancer mortality among Hispanic and Latino groups (Hispanic/Latinx). Despite making up 18.9% of the U.S. population, Hispanic/Latinx representation is only 2.3%-3.9% of subjects in oncology trials, highlighting the need for diversity in CRC research. Freenome is developing a blood test (MyTectCRC) intended to provide a convenient and accessible option for CRC screening. Its clinical validation will be supported by PREEMPT CRC, a prospective multi-center observational study. To ensure a diverse enrollment, Freenome partnered with several sites, including IHS, in communities with a diverse population. This analysis explores strategies used at IHS Health to effectively enroll minority groups. Methods: Initiated in 2020, PREEMPT CRC study (NCT04369053) enrolled participants aged 45-85 at average CRC risk. Eligible and consenting participants underwent a blood draw and a screening colonoscopy (CS), with the blood sample analyzed by Freenome using the investigational blood test. IHS Health, a research institute in Kissimmee, Florida, utilized a variety of methods to maximize the enrollment of diverse populations reflective of its local communities, such as partnering with local organizations to establish community outreach and employing bilingual staff to translate, educate, answer study questions, with cultural sensitivity. Participants were also able to have blood drawn and undergo CS on the same day due to its proximity to a gastroenterology office. Results: The site of IHS Health enrolled 427 participants in the PREEMPT CRC study, including substantial representation of Hispanic/Latinx (78.7%) which exceeded their proportional representation in the U.S. population. The self-reported race of enrolled participants was predominantly White (71.2%), with a significant proportion of Black or African American (24.1%). The age distribution showed higher enrollment for the 65-74 age group, emphasizing inclusivity for older populations characteristic of the catchment area. Participants exhibited healthy lifestyle behavior with the majority of the population abstaining from tobacco (88.8%), alcohol (84.1%) or drug use (99.5%). Participants were very receptive to the blood test/CS with all undergoing blood draw and 96% CS adherence. Conclusions: The results underscore the success of IHS Health's recruitment methods in addressing health disparity by emphasizing the importance of inclusivity in clinical trials, leading to high enrollment of Hispanic/Latinx, reflective of local demographics. Success of PREEMPT CRC study highlights the need for careful site selection, robust recruitment strategies, and practical accessibility for patients to ensure a comprehensive understanding of medical interventions across diverse populations. Clinical trial information: NCT04369053 .
MET exon 14 skipping in NSCLC: An unMET Indian need.
Authors: Batra Ullas , Nathany Shrinidhi , Sharma Mansi , Patel Amrith , Mehta Anurag , Mattoo Sakshi , Noronha Vanita , Prabhash Kumar
Published: May 2024

e13537

Background: The approval of capmatinib and tepotinib, selective MET tyrosine kinase inhibitors (TKI), has further shifted the therapeutic paradigm of advanced NSCLC. MET exon 14 skipping (MET ex14) alteration is a complex mechanism, reported in ~3-4% cases of NSCLC. Controlled trials have reported remarkable outcomes of selective MET TKIs, however real world outcomes from this part of the world are currently lacking. Methods: This is a non-interventional study reporting real world outcomes of NSCLC with MET ex14 from two apex cancer centers of India. 49 eligible patients were recovered from the electronic medical record archives. All cases with MET ex14 were included irrespective of clinicopathologic characteristics and therapy offered. Statistical analysis was performed using R studio. Results: Clinical characteristics are shown (Table). Treatment patterns were heterogeneous across therapy lines and included chemotherapy, MET TKIs and immune checkpoint inhibitors. 42/49 patients opted for treatment; rest dropped out owing to economic restraints. 1st line TKI was offered to 14 patients, and chemotherapy to 28 patients. 1st line PFS of TKI treated was 11.9 months (95%CI:5.8-17.8) vs. 5.9months (95%CI: 3.9-16.8) (p<0.002*) for the chemotherapy treated cases (HR for TKI: 0.3295 (95%CI: 0.1630 to 0.6663). Presence of TP53 co-mutation and male gender and were factors affecting 1st line PFS (p<0.06) on multivariate analysis. 2nd line treatment was opted by 13/14 patients in TKI treated group of which 5 received sequential TKI, and 8 received chemotherapy and 22/28 in chemotherapy treated group (TKI: 14, chemotherapy: 8). PFS for 2nd line TKI was 7.7 months (95%CI: 2.8-14.8) vs 4.6 months (95%CI:2.1-9.8) for chemotherapy {HR for TKI: 0.3641 (95%CI: 0.1378 to 0.9616)} (p<0.04*). The dropout rate from 1st to 2nd line was 36% and 44% in subsequent line. 28 (57%) received MET TKI at any given point in disease course. Median OS for patients treated with 1st line TKI was not reached at study end (95%CI: 9.2-NR) and was 20.7 months (95%CI:18.1-36.1) for chemotherapy (p=0.3). One year and 2 year survival rates for 1st line TKI and Chemotherapy were 86%vs 73% and 47% vs 45%, respectively. Conclusions: This is the largest cohort from India reporting real world uptake of TKI therapy in MET ex14 altered NSCLC. There is a blaring disparity with respect to accessibility of drugs, as well as prevailing socioeconomic restraints. This study clearly depicts an unmet need for more global clinical trials for rare genomic alterations as well as patient access programs in this part of the world. [Table: see text]
Clinicians' experiences and perspectives of a web-based lung cancer referral pathway.
Authors: Otty Zulfiquer Ali , Sabesan Sabe S. , Larkins Sarah , Evans Rebecca , Brown Amy
Published: May 2024

e13539

Background: Efficient and streamlined referral of patients with suspected lung cancer is an integral part of providing optimal care for these patients. There is emerging evidence that use of online care pathways, such as HealthPathways is associated with improved referral quality from primary care, more timely access to secondary care and standardization of clinical management decisions by general practitioners (GPs). The Townsville Lung Cancer Referral Pathway (TLCRP) is part of ' Townsville HealthPathways', which is the evidence-based clinical pathway portal used in the Townsville Hospital and Health service in northern Australia. This study aimed to explore the experiences and perspectives of clinicians about TLCRP. Methods: This was a descriptive qualitative study nested within a larger project evaluating TLCRP, utilising a broader implementation science framework. In-depth, semi-structured interviews of GPs and lung cancer specialists were conducted. An iterative, inductive thematic analysis of interview transcripts was undertaken to derive key codes and themes regarding participant experiences and perceptions. Results: Twenty interviews were conducted, 14 with GPs and six with specialists across disciplines of respiratory medicine, oncology, and cardiothoracic surgery. Of the GPs, 11 were practicing in the regional locality of Townsville and three practiced in surrounding rural areas. Interview analysis identified two major themes and several sub-themes (Table). Several enablers and barriers to implementing TLCRP were identified. Barriers to adaptation of TLCRP included lack of clinical time, resistance to changing referral patterns, lack of familiarity or experience with HealthPathways and technology issues. Enablers included clinical usefulness of TLCRP, support from HealthPathways implementing team, integration of TLCRP with the electronic referral system and positive feedback from specialists. Conclusions: Emerging themes from this study may be used to reduce the barriers and improve uptake of TLCRP and other health care pathways in the local health service. Improving the uptake of TLCRP may mean that more patients in our region experience a streamlined journey to more timely specialist lung cancer care and improved health outcomes. [Table: see text]