bluuebunny/crossref_metadata_2025 huggingface dataset:
Mobile health–supported comprehensive intervention model (CIMmH) improved physical fitness of patients with esophageal cancer after esophagectomy: Prospective randomized controlled trial.
Authors: Yang Weixiong , Guo Yan , Deng Chuanbao , Zhuo Shuyu , Liang Qi , Huang Zihao , Zhang Nanxiang , Lin Xiaotong , Li Yingqi , Yu Chuanchuan , Xu He , Li Yiran , Tang Ziyue , Liu Yao , Fang Zengli , Chen Wenfang , Zhang Shuishen , Zeng Bo , Yeung Saiching Jim , Cheng Chao
Published: May 2024

1634

Background: Esophageal cancer (EC) significantly impacts patients’ quality of life (QOL) post-esophagectomy, with malnutrition, reduced physical activity, and psychological distress being common. Our preliminary study indicated that a Mobile Health-Supported Comprehensive Intervention Model (CIMmH) is safe, feasible, and efficacious in improving QOL and physical fitness for EC patients. This randomized controlled trial (RCT) evaluates the effectiveness of CIMmH in promoting post-surgery recovery for EC patients. Methods: EC patients undergoing modified McKeown esophagectomy were randomly allocated to either the intervention group, receiving the CIMmH protocol (nutrition, exercise, psychological support), or the control group, receiving standard postoperative care. Outcomes were assessed at baseline, 1 month, and 3 months post-surgery. Key metrics included sarcopenia (assessed via skeletal muscle index and psoas muscle thickness on CT scans), quality of survival (EORTC-QLQ-C30 and EORTC-QLQ-QES-18), physical fitness (six-minute walk distance, SMWD), and nutritional status (body weight). Results: Of 111 screened patients, 80 were enrolled (40 per group). Follow-up assessments were completed by 76 patients at 1 month and 69 at 3 months. At 1 month, the intervention group showed a significant improvement in SMWD compared to the control group ( P=0.020), though no difference was observed at 3 months ( P=0.835). The intervention group also demonstrated a significant increase in the skeletal muscle index at 3 months ( P=0.039), alongside notable improvements in the 30-second arm curl test and cough symptom relief ( P=0.027 and P=0.045, respectively). No significant differences in QOL scores or body weight were observed between groups at any time point. Conclusions: CIMmH significantly enhances short-term physical fitness in EC patients post-esophagectomy. These findings suggest the need for further refinement and optimization of the intervention to maximize its long-term effectiveness and impact on QOL. Clinical trial information: ChiCTR2000041007 .
Clinical relevance of clinical treatment score post 5 years (CTS5) in HR-positive, HER2-positive breast cancer: An exploratory analysis from the HERA trial.
Authors: Bae Soong June , Moon Sohyun , Kook Yoonwon , Baek Seung Ho , Lee Min Ji , Kim Jee Hung , Ahn Sung Gwe , Jeong Joon
Published: May 2024

519

Background: The clinical treatment score post-5 years (CTS5) has proven valuable in assessing the necessity for extended endocrine therapy among patients with early-stage hormone-receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer. This study aimed to explore the potential of CTS5 as a predictive tool for long-term survival beyond five years in patients with specifically HR-positive, HER2-positive breast cancer. Methods: We collected patient-level data from the HERceptin Adjuvant (HERA) (BIG1-01; NCT00045032) trial. Our investigation focused on assessing the risk of late distant recurrence (DR) and overall survival (OS) according to the CTS5 risk score as continuous value and CTS5 stratification risk groups. Furthermore, we performed a Cox-regression analysis to determine the prognostic performance of CTS5, stratifying subgroups by age and administration of trastuzumab. Results: A total of 1,818 patients with HR-positive, HER2-positive breast cancer were included in this analysis. The CTS5 score, as a continuous variable, emerged as an independent prognostic factor for both late DR (adjusted HR, 2.04; 95% CI, 1.62-2.57; P < 0.001) and OS (adjusted HR, 2.02; 95% CI, 1.58-2.58; P < 0.001), respectively. In addition, multivariable analysis showed a significant association between the high-risk group and adverse outcomes in late DR (adjusted HR, 2.76; 95% CI, 1.84-4.15; P < 0.001) and OS (adjusted HR, 2.45; 95% CI, 1.60-3.74; P < 0.001) compared to low/intermediate group. Consistent results were observed, regardless of age or administration of HER2-targeted therapy. Conclusions: CTS5 is a useful prognostic tool for predicting late DR and OS in HR-positive, HER2-positive breast cancer patients. Extension of endocrine therapy should be actively considered in patients with CTS5 high-risk group.
Impact of young age at diagnosis on survival outcomes in patients with early breast cancer according to tumor subtype: Pooled analysis of 5 randomized clinical trials from the Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM).
Authors: Perachino Marta , Blondeaux Eva , De Laurentiis Michelino , Arpino Grazia , Puglisi Fabio , Fabi Alessandra , Gori Stefania , Poggio Francesca , Arecco Luca , Favero Diletta , Sydes Matthew R. , Lambertini Matteo , Del Mastro Lucia
Published: May 2024

523

Background: The incidence of breast cancer (BC) among young patients is increasing. Historically, young age itself has been recognised as a poor prognostic factor for BC. However, there is limited evidence regarding the impact of age at diagnosis and on survival outcomesaccording to tumor subtype. Methods: We collected individual patient (pt)-level data from newly diagnosed stage I to III BC pts participating in 5 randomized clinical trials conducted by Mammella InterGruppo (MIG) and Gruppo Italiano Mammella (GIM) study groups. Patients were categorized into the following age groups based on their age at BC diagnosis: ≤40, 41-50, 51-60, 61-70, >70 years (yr). Multivariable Cox proportional hazards models were used to assess the relationship between age and breast cancer–free interval (BCFI) and breast cancer specific survival (BCSS). Results: 8,338 pts with stage I to III BC were included in the study: 778 (9%) aged ≤40 years, 1629 (20%) 41-50 years, 2,595 (31%) 51-60 years, 2,435 (29%) 61-70 years, and 901 (11%) >70 years. Compared to older, young pts were more likely to have ductal tumors as histology, larger than 2 cm, with nodal involvement, G3 and triple negative or HER2 positive subtypes (p<0.001). With a median follow-up of 9.0 years (IQR 5.5-14.4), 2,161 BCFI and 927 BCSS events were observed in the overall population. Pts ≤40 years at diagnosis had greater risk of reporting BC event (adjusted hazard ratio (adjHR) for BCFI 1.27, 95% CI 0.93-1.74) compared to pts aged 51-60 years (reference group), while pts 41-50 years had a lower risk (adjHR 0.74, 95%CI 0.55-0.99). Pts aged ≤40 years presented some evidence of a lower risk of BCSS events (adjHR 0.80, 95%CI 0.50-1.26) compared to pts aged 51-60 years, while pts aged 41-50 years had the lowest risk (adjHR 0.50, 95%CI 0.32-0.78). There was evidence of interaction between age and tumor subtype, nodal status both for BCFI and BCSS. A significant increase in risk of BC events was observed among pts ≤40 years with hormone-receptor positive/HER2 negative tumors (HR 1.70 for BCFI) and among ≤40 years with node negative tumors (HR for BCFI 2.43). Conclusions: The prognostic significance of young age at diagnosis may vary depending on tumor subtypes and nodal status, indicating poorer outcomes for young pts with hormone-receptor positive/HER2 negative and node negative tumors.
An initial experience of robot-assisted breast conserving surgery: A multicenter study of the Korea Robot-Endoscopy Minimal Access Breast Surgery Study Group (KoREa-BSG).
Authors: Choi Hee Jun , Paek Se Hyun , Lee Jun-Hee , Kim Ku Sang , Kim Hyun Yul , Park Hyung Seok , Ryu Jai Min
Published: May 2024

543

Background: Robot-assisted breast conserving surgery (RABCS) have cosmetic benefit without any scar on the breast over conventional breast conserving surgery (CBCS). However, data on the feasibility and safety of the RABCS are limited. The aim of this study was to present the results of early experience of RABCS. Methods: A multi-center retrospective review was conducted to identify women who underwent RABCS as part of the Korea Robot-Endoscopy & Minimal Access Breast Surgery Study Group (KoREa-BSG) between August 2019 and October 2023. Information of the clinicopathologic characteristics, perioperative complications, operation time, recurrence, and re-operation were collected. Results: A total of150 patients underwent the RABCS procedure conducted by 10 breast surgeons at seven institutions. Invasive breast cancer was noted in 121 cases and ductal carcinoma in-situ was detected in 29 cases. Further, 75.3% and 65.3% of the patients had an estrogen and progesterone receptor positive status, respectively. A total of 35.3% of the patients had a HER2-positive status. In terms of the surgical technique, the Da Vinci SP system was more frequently used (60%). Gas insufflation was applied in 97.33% of the cases, and s entinel lymph node biopsy (SLNB) only was the most common axillary surgery (89.3%). The median duration of postoperative days was 5.4 days (range, 1.0-15.0 days). The incision location was the mid-axillary line and the median incision length was 37.1 mm (range, 27.0-60.0 mm). The median total operation time was 133.8 minutes (range, 62.0-295.0 minutes). 11 cases (7.3%) showed frozen margin positive, however only one case (0.7%) required re-operation because of permanent margin positive. Six patients (4%) developed surgical complications. Postoperative bleeding was found in one case and skin burn was found in five cases (3.3%); two cases (1.3%) required skin excision and three cases (2.0%) showed spontaneous resolution. There were no cases of conversion to open surgery or mortality. Only one case (0.7%) had recurrence. Conclusions: This was the first multicenter report of RABCS in the world. RABCS could be a technically feasible and safe. Further subsequent comparative study with CBCS and prospective research are needed to evaluate the surgical and oncologic outcomes.
Evaluating the association between radiomic features on breast MRI and dormant tumor cell presence in the SURMOUNT trial.
Authors: Slavkova Kalina Polet , McDonald Elizabeth S. , Cohen Eric A. , Pantalone Lauren , Bayne Lauren , Nivar Isoris , Sanchez Pauleen , Mankowski Walter C. , Brown Melanie , Clark Amy Sanders , Rohn Killian , Chodosh Lewis A. , Kontos Despina , DeMichele Angela
Published: May 2024

561

Background: While breast cancer treatment is effective at eradicating primary disease, approximately 20% of patients will ultimately recur at a distant site. Recurrence has been linked to the presence of minimal residual disease (MRD) after treatment, which presents as circulating micrometastases and dormant tumor cells (DTCs) located primarily in the bone marrow. Radiomic features on MRI are imaging biomarkers that have been linked with lesion heterogeneity, which in turn has been associated with disease aggressiveness. Here, we examine the association between radiomic features from the primary lesion on MRI and the presence of post-treatment DTCs. Noninvasively identifying patients at high risk of MRD would facilitate optimized treatment strategies to reduce recurrence risk. Methods: Dynamic contrast-enhanced MRI data from breast cancer survivors enrolled in the SURMOUNT trial (N=104) were retrospectively analyzed. Participants with MRIs collected within 90 days of diagnosis who consented to provide a bone marrow aspirate (BMA) sample were eligible. Working with a board-certified radiologist, we successfully identified and segmented the primary lesion for N=70 patients with BMA outcomes. Using the publicly available CaPTk software, we computed 33 radiomic features for each segmented lesion based on pixel intensity, morphology, and grey level textures. To reduce the dimensionality of the feature space, we used these feature values to group the participants into clusters—termed radiomic phenotypes — via agglomerative hierarchical clustering with significance testing. Fisher’s exact test was applied to test the statistical significance of the association between radiomic phenotype and BMA outcome (± DTC). For all statistical tests, p<0.05 was considered significant. Results: Of the N=70 participants analyzed, 58 were negative and 12 were positive for DTCs present in the bone marrow. Two statistically significant radiomic phenotypes ( p<0.05) were identified that were strongly associated with BMA outcome ( p=0.0251). 11 out of 12 positive outcomes were grouped into the second radiomic phenotype (Table). Conclusions: We found a statistically significant association between DTC presence and radiomic phenotypes derived from MRI data. Given the large percentage of positive outcomes assigned to the second radiomic phenotype, the radiomic phenotypes may indicate low and high risk of MRD, respectively. Importantly, this analysis shows promise for the ability to predict MRD from noninvasive imaging features. These results motivate continued data collection to increase sample size and identify a robust set of radiomic features, which may ultimately be used as predictors in potential models of MRD risk. [Table: see text]
Nectin-4 expression in primary breast cancer and associated clinical outcomes.
Authors: Medford Arielle J , Niemierko Andrzej , Abelman Rachel Occhiogrosso , Haradhvala Nicholas , Knape Justine , Spring Laura , Getz Gad , Bardia Aditya
Published: May 2024

570

Background: Antibody-drug conjugates (ADC) selectively deliver chemotherapy to tumor cells expressing a target antigen. Currently approved ADCs in breast cancer target HER2 or Trop-2. Enfortumab vedotin, an ADC targeting Nectin-4, a cell adhesion molecule, is approved in advanced/metastatic urothelial cancer. This study evaluated the expression landscape of Nectin-4 in breast cancer and its association with clinical outcomes. Methods: Processed mRNAseq data was assessed for expression of the gene encoding Nectin-4 in primary breast cancer tissue and adjacent normal breast tissue from The Cancer Genome Atlas (TCGA), and normal tissue from the Genotype-Tissue Expression (GTEx) Project. Low gene expression was determined as <100 transcripts per million (TPM). TCGA samples had been annotated for putative copy-number alterations using GISTIC 2.0; genes with a score of 2 were marked as amplified. Multivariable Cox regression analysis was used to analyze the association of low vs medium/high gene expression with disease-free survival (DFS) and overall survival (OS), adjusting for age, stage, and subtype. Results: RNA-Seq data was available for 1086 patients with primary breast cancer, including known hormone receptor positive (HR+)/HER2- (n=530), HER2+ (n=112), and triple negative breast cancer (TNBC) (n=120). NECTIN4was amplified in 15% of cases (n=165): 15% (n=78) in HR+, 15% (n=17) in HER2+ and 21% (n=25) in TNBC. NECTIN4 expression was medium/high in 356 (33%) patients: 149 (28%) HR+/HER2- (median 77.8 TPM, IQR 50.1-116.5), 32 (29%) HER2+ (median 73.7 TPM, IQR 51.9-107.8), and 59 (49%) TNBC (median 99.7 TPM, IQR 57.8-148.3). Median expression in normal breast tissue was 47 TPM (TCGA) & 16.74 TPM (GTEx), and highest in normal skin at 205 TPM. In multivariable analysis, medium/high NECTIN4 expression was associated with worse OS (HR 1.96, 95% CI 1.32-2.99, p<0.001). As a continuous variable, increasing NECTIN4 expression levels were associated with worse OS. After correcting for age, stage and subtype, for each 10-unit increase in NECTIN4TPM, the risk of death increased by 5% (HR 1.0050, 95% CI 1.0028 - 1.0072, p < 0.001). Conclusions: NECTIN4 expression was higher in TNBC and associated with worse overall survival. The high expression level in normal skin possibly contributes to the cutaneous toxicity associated with enfortumab vedotin approval and requires careful consideration as ADCs targeting Nectin-4 are developed to target breast cancer.
Artificial intelligence (AI) –powered H&E whole-slide image (WSI) analysis to predict recurrence in hormone receptor positive (HR+) early breast cancer (EBC).
Authors: Moon Jimin , Lee Hyunwoo , Cho Yoon Ah , Park Gahee , Jung Wonkyung , Kim Seulki , Shin Jiwon , Park Jiyoung , Park Jongchan , Yoo Donggeun , Pereira Sergio , Ahn Chang Ho , Cho Eun Yoon
Published: May 2024

571

Background: The recurrence risk (RS) based on transcriptomic profiles or Ki-67 level of HR+ EBC has been used for adjuvant treatment decisions and may also aid selecting patients who could benefit from novel treatments including CDK4/6 inhibitor or oral selective estrogen receptor degraders (SERDs). Artificial intelligence-powered H&E whole slide image (WSI) models can be a practical approach for this biomarker without the need of additional tissue samples. We developed ML-based models of histopathologic features from an H&E WSI to approximate RS of 21-gene assay (OncotypeDx) using various algorithms of different complexities. Methods: The development dataset was composed of 1,009 cases from TCGA-BRCA with gene expression profiles and 483 EBC cases from Samsung Medical Center with RS results. The prediction model was developed in two-stages. First, Lunit SCOPE, an AI-powered H&E WSI analyzer, detects various cell types and segments tissue areas resulting in various cell densities in tissue regions of interest. Next, four traditional ML models were applied on top of the first stage results. In addition, a deep learning model based on multiple instance learning (DL-MIL) was developed using three features: a supervised convolutional neural network, a supervised cell detection model, and an AI-based pathology profiling analyzer, for extracting semantic contents. The model performance was validated using two independent EBC test sets: 248 cases for comparison with the RS results (set 1), and 708 cases with DFS (set 2). Results: The cross-validation performance of the four traditional ML algorithms had area under the curve of receiver operating characteristics curve (AUROC) ranging from 0.728 to 0.779, where mitotic cell density, tumor cell density, and fibroblast density in cancer area were the variables with the highest importance for all four models. The DL-MIL model had cross validation performance of AUROC 0.831. In test set 1, DL-MIL model showed the highest discrimination with AUROC of 0.828 compared to traditional ML models where logistic regression showed the highest discrimination with AUROC of 0.786 (Table). The DL-MIL model showed the highest performance among the models to predict DFS with hazard ratio (HR) of 2.48 (1.47-4.18). Conclusions: Histopathomic models can accurately predict the RS of high risk as well as poor DFS from only H&E WSIs. These AI models can be a practical tool for treatment selection including emerging drugs such as SERDs. [Table: see text]
Memory mayhem: Hormone therapy causing brain fog in patients with DCIS.
Authors: Desai Devashish , Ashok Kumar Prashanth , Benjamin Sam
Published: May 2024

575

Background: Long term hormonal therapy in ductal carcinoma in situ (DCIS) have been studied without consistent evidence to cause cognitive side effects. Here we evaluate the relation of using hormonal therapy (HT) in patients with DCIS with cognitive effects. Methods: TrinetX, a global federated research network that provides a dataset of electronic medical records from different healthcare organizations (HCOs), was utilized. Initial query was made to isolate patients who had an ER positive DCIS. Two groups were made based on the receipt of hormone therapy (exemestane, tamoxifen, letrozole, anastrozole). Further, propensity score matching (PSM) was carried out to match age, sex, race, development of malignant neoplasm of breast, chemotherapy at any point. Outcomes of cognitive impairment were identified using ICD 10 CM codes R41.3, R41.0, F05, F02.81, and Alzheimer’s dementia was identified using ICD 10 CM code G30. Compare outcome analytic function was utilized to map the co-relation of HT with cognitive impairment. Results: 64,266 patients were identified with ER positive DCIS, of whom 63.18% (n=40,601) received HT. Patients who received HT were older (61.4 ± 12.3 vs. 61 ± 12.9, p<0.0001), and predominantly Caucasian (70% vs 65%, p<0.0001). On looking further into racial distribution of population, it was seen that Caucasians were predominant in both groups, followed by African Americans (12% vs. 11%, p=0.0016) and Unknown race (11% vs. 17%, p<0.0001), then Asians (4% vs. 4%, p=0.0675). Before PSM, it was seen that 7.55% (n= 2,818) patients had cognitive side effects compared to only 5.044% (n= 1,139) in group that did not receive HT (OR 1.537 (1.432,1.65), p<0.0001). Log-Rank Test for Kaplan-Meier curve was significant for the difference with hazard ratio 1.315, (1.227,1.409). A similar association was seen with Alzheimer’s dementia (0.735% vs. 0.547%, OR 1.346 (1.094,1.656), p= 0.0048) but Kaplan-Meier survival analysis did not show any significant difference between the groups. After PSM, both groups had 15,801 cases. The odds of developing cognitive impairment was higher in HT group (6.582% vs. 5.589%, OR 1.19, (1.082,1.309), p=0.0003). But Log-Rank Test for Kaplan-Meier curve did not show any significant difference (HR 1.047 (95% CI 0.954-1.149)). There was no significant difference for Alzheimer’s dementia development in either group (0.769% vs. 0.591%, 1.303 (0.994,1.709), p = 0.0548). Conclusions: Our study shows that HT significantly increases the odds of developing cognitive impairment. The limitation of the study is the duration of follow up. Usually, patients with DCIS live much longer and can have cognitive effects beyond the window of this study; hence a prospective long-term follow-up study is required to ascertain the relation of HT and cognitive side effects. Patients when starting the treatment should be counselled about the risk of developing cognitive side effects in future.
Therapeutic response and outcomes with less common breast cancer subtypes in the I-SPY trial 2011-2022.
Authors: Thomas Alexandra , Wolf Denise M. , Balassanian Ronald , Chen Yunn-Yi , Ye Julia , Vohra Poonam , Gulbahce Evin H , Borowsky Alexander D. , Brown Swigart Lamorna , Hirst Gillian L. , Venters Sara , Nanda Rita , Shatsky Rebecca Arielle , D'Agostino Ralph , Mukhtar Rita A. , Hatcher Sarah , Yau Christina , DeMichele Angela , van 't Veer Laura , Esserman Laura
Published: May 2024

582

Background: Uncommon histologies are over-represented among high-risk breast cancer (BC) and denote an area with limited trial data and of significant unmet medical need. To better understand trial outcomes in this group and identify signals of tumor responsiveness, we report pathologic complete response (pCR) and early event-free survival (EFS) by disease subtype in the I-SPY2 trial. Additionally, the I-SPY2 trial currently utilizes a combination of tumor molecular signature and receptor status to determine response predictive subtype (RPS) first developed from 987 I-SPY2 patients (1). We report disease response rates for those who received what is now known to be optimal RPS guided therapy. Methods: The I-SPY2 platform trial tests novel agents given neo-adjuvantly with a chemotherapy backbone in high-risk BC (HER2 positive, triple negative and high molecular risk estrogen receptor positive BC). Histologic images of research biopsies, local biopsy and surgical pathology reports were reviewed centrally by I-SPY pathologists. Receptor subtype distribution and pCR rates were summarized. EFS was estimated using the Kaplan Meier method. Association between pCR and EFS was evaluated using the Cox proportional hazard model with significance assessed by the log rank test. Results: 144/2118 (7%) of I-SPY2 participants were identified with metaplastic (60), lobular (55), mucinous (9), micropapillary (8), neuroendocrine (4) and other (8) BCs. Tumor receptor status, pCR rate and EFS by tumor type are shown in the Table. For the full cohort, pCR was associated with better EFS (hazard ratio (95% CI): 0.12 (0.02 - 0.88), p = 0.01). Within metaplastic (metapBC) 11/32 (34%) and 5/28 (18%) patients had a pCR with or without checkpoint blockade, respectively. By RPS group, 9 of 18 (50%) (13 metapBC, 3 other, 2 lobular) in the HER2-Immune+ group who received RPS optimized therapy had a pCR. In this group 6/13 (46%) with metapBC had a pCR. In the HER2+ driven RPS groups, pCR rate in the HER+HER2orBasal was 88% (7/8) and 0% (0/3) in the HER2+Luminal. Conclusions: High pCR rates observed in metapBC and other among subsets of often difficult to treat BC subtypes support novel approaches and provide a roadmap for future study of uncommon BCs. Outcomes were improved when therapy matched RPS vulnerabilities. Participants presenting with uncommon BC subtypes will be prospectively identified in the I-SPY2.2 trial to further develop effective approaches for this group. 1. Wolf et al, Cancer Cell 2022. Clinical trial information: NCT01042379 . [Table: see text]
An MRI-based multi-parameter clinical decision support system (NeoMDSS) for early prediction of pathological complete response after the first cycle of neoadjuvant therapy in breast cancer: A multi-center prospective observational cohort study.
Authors: Zhang Liulu , Zhu Zhaowen , Chen Yuanqi , Wu Yidan , Zhang Yongcheng , Ye Guolin , Li Wei , Wang Kun
Published: May 2024

592

Background: Currently, there is no reliable and convenient way to predict response rates in early stages of neoadjuvant therapy (NAT) for breast cancer, which can affect the prognosis of non-responsive patients. Methods: In this prospective multi-center observational study, eligible participants who underwent NAT followed by radical surgery were recruited. All patients underwent magnetic resonance imaging (MRI) examination before and after the first cycle of NAT (1st-NAT). We analyzed the effects of clinicopathological features, such as histological grade, hormone receptor (HR) and HER2 status, Ki-67 expression, blood cell analysis, and MRI parameters including the reduction ratio of tumor diameter (ΔD%), apparent diffusion coefficient (ADC), and early enhancement ratio (EER) on NAT. By incorporating independent influencing factors, we developed a multiparametric clinical decision support system (NeoMDSS) model based on a retrospective cohort and validated its accuracy in both a prospective single-center internal cohort and a prospective multi-center external cohort. Relevant clinical trial details can be found under the identifier NCT04909554. Results: A total of 301 breast cancer patients were enrolled between January 2019 and December 2023, including 140 patients in the training cohort, 120 patients in the internal validation cohort, and 41 patients in the external validation cohort. The NeoMDSS model demonstrated excellent performance in predicting pathological complete response (pCR) at 1st-NAT, with an AUC of 0.874 (95% CI 0.813-0.935) in the training cohort, 0.845 (95% CI 0.771-0.919) in the internal validation cohort, and 0.867 (95% CI 0.742-0.992) in the external validation cohort. The NeoMDSS model exhibited a sensitivity, specificity, and accuracy of 80.0%, 81.3%, and 80.5%, respectively, in the internal validation cohort, and 87.0%, 83.3%, and 85.4%, respectively, in the external validation cohort. Calibration curves and decision curve analysis (DCA) further supported the clinical value of the NeoMDSS model. To facilitate the clinical application of the NeoMDSS model, a nomogram and an online website ( www.gdphneomdss.com ) were developed to calculate the probability of pCR, which the sensitivity, specificity, and accuracy of the NeoMDSS model were all 80.0% in the internal validation cohort and 80.0%, 81.3%, and 80.5% in the external validation cohort. Conclusions: The NeoMDSS model serves as a convenient tool in clinical practice at 1st-NAT to calculate and accurately predict the probability of pCR after NAT. This assists clinicians in determining whether to modify the treatment plan and improving personalized treatment for patients with poor response to NAT. Clinical trial information: NCT04909554 .
Real life comparison between doxorubicin and cyclophosphamide (AC) dose-dense (dd) and conventional dose AC in patients with triple negative breast cancer (TNBC) under neoadjuvant treatment.
Authors: Cavalcanti Balint Flavia , Tavares Monique Celeste , Sousa Isadora Martins de , Marin Comini Ana Carolina , Borges Italo Barradas e Silva , Coimbra Barroso Matheus , Martins Livia Alexandre , de Albuquerque e Rodrigues de Sousa Débora Guilherme
Published: May 2024

e12662

Background: High-risk early triple-negative breast cancer (TNBC) is frequently associated with early recurrence and high mortality. Studies suggest a sustained clinical benefit in patients with TNBC who have a pathological complete response (PCR) after neoadjuvant chemotherapy (NACT). The dose-dense (dd) regimen demonstrated improved survival regardless of hormone receptor expression or HER2 status. The doxorubicin and cyclophosphamide (AC) regimen can be performed in (dd), therefore it must include granulocyte growth factors, which may increase costs and toxicities. The object of the study was to evaluate their clinical characteristics and treatment, patients with TNBC, stage I-III who received ACdd in neoadjuvant treatment versus patients who received AC dose conventional (dc). Methods: We performed a retrospective observational cohort study of patients with early TNBC, stage I-III who received neoadjuvant treatment with chemotherapy based on doxorubicin, cyclophosphamide, paclitaxel and carboplatin associated with pembrolizumab. Results: All 82 patients were women 57.3% received ACdd, 30.4% received AC dc. In group ACdd 59.5% had intercurrence related with chemotherapy, in which 17.8% were neutropenic fever and 21.4% had developed different types of infections (ex: diarrhea, pneumonia and others). In these 2 groups all of them had received antibiotic. About 50% of the patients had developed intercurrence because of treatment toxicity and just 3.5% had disease progression. The other group that we evaluated is composed by patients who ACdc, dose Regarding to these group 48% developed any intercurrence during the neoadjuvant treatment, in which 8.3% had neutropenic fever and 25% had different types of infections. All of them earned antibiotic. About clinical and pathological response, the group that earned ACdd 61.7% got complete clinical response and 8.5% had a disease progression during the treatment. In the other arm 68% got complete clinical response and 4% had a progression. Conclusions: AC dd was more prevalent in our series, despite the additional use of granulocyte growth factor, there were more complications in this group and it did not demonstrate better results than those who received conventional dose AC.
Trends and outcomes in patients receiving neoadjuvant chemotherapy for breast cancer in Ontario: A population-based study.
Authors: Castelo Matthew , Nguyen Lena , Roberts Amanda
Published: May 2024

e12664

Background: Modern neoadjuvant chemotherapy (NAC) regimens in breast cancer offer higher rates of pathologic complete response, an ability to guide further adjuvant treatment, and may de-escalate surgery. However, the utilization of NAC has been heterogeneous in Ontario. This study aimed to describe trends in NAC use in Ontario, report survival outcomes, and explore factors associated with overall survival in these patients. Methods: This was a population-based cohort study using linked health administrative data in Ontario, Canada. From the Ontario Cancer Registry, we identified women ≥18 years who underwent neoadjuvant chemotherapy followed by surgery for operable (cT1N1, cT2-3N0, or cT2-3N1) breast cancer between 2012 and 2020. Patients were divided by receptor subtype (triple negative breast cancer [TNBC], ER+/HER2-, ER+/HER2+, ER-/HER2+) and characteristics were compared using standardized mean differences (SMDs). Five-year overall survival (OS) and breast cancer-specific survival (BCSS) were determined and reported for each subtype. Associations with OS and BCSS were calculated for patient and disease characteristics using univariate and multivariable Cox proportional hazards models and Fine and Gray models, respectively. Results: 3,804 women underwent NAC for cT1N1, cT2-3N0, or cT2-3N1 breast cancer in Ontario between 2012 and 2020. The largest contributing subtype was ER+/HER2- patients (39.3%) followed by those with HER2+ disease (ER-/HER2+ 13.8%, ER+/HER2+ 23.4%), and TNBC (23.5%). The median age was 50 years (IQR 42-59 years). Most patients were clinically node-positive (2,736; 71.9%), and underwent mastectomy (2,397; 63.0%). There was a significant increase in the number of patients receiving NAC in Ontario, from 217 in 2012 to 667 in 2019 ( p<0.001), with a greater increase among patients with TNBC or HER2+ disease. Compared to those with ER+/HER2- disease, TNBC patients were treated for smaller tumours (28.6% T3 vs. 39.8%; SMD = 0.24), and were more likely to be node-negative (39.1% N0 vs. 22.1%; SMD = 0.38). Similar trends for nodal status were found for patients with ER-/HER2+ (26.7% N0) and ER+/HER2+ cancer (27.9% N0). 5-year OS for the entire cohort was 88.1% (95% CI 87.1 – 89.2%). Survival was highest for ER+/HER2+ patients (94.2%, 95% CI 92.6 – 95.8%) and lowest for TNBC patients (80.1%, 95% CI 77.5 – 82.8%). Similar patterns were seen for BCSS. Factors associated with OS in a multivariable model included older age (increase in 5 years HR 1.1, 95% CI 1.07 – 1.14), N1 status (HR 1.99, 95% CI 1.61 – 2.47), larger tumour size (T3 HR 1.83, 95% CI 1.34 – 2.5), mastectomy (HR 1.45, 95% CI 1.2 – 1.75), and TNBC (versus ER+/HER2- HR 1.9, 95% CI 1.56 – 2.32). Conclusions: The use of NAC has increased in Ontario, particularly among TNBC and HER2+ patients. Women with TNBC have worse outcomes compared to those with ER+/HER2- disease, despite being treated for less advanced disease.
FIT as a population-based and financially viable method to screen underserved patients for colorectal cancer.
Authors: Grivas Christopher , Ifrah Abraham , Dahake Nikita , Vallabhaneni Manasa , McNeilly Shelby , Graham Brianna , Gillow Gabrielle , Khatri Rishabh , Raab Claire
Published: May 2024

e13516

Background: Temple University Hospital (TUH) created an initiative to increase colorectal cancer (CRC) screening by administering fecal immunochemical tests (FIT) to the underserved population of Philadelphia. We hypothesize that this will increase the percentage of diagnostic colonoscopies performed compared to baseline in our fixed capacity colonoscopy suite and ultimately generate a higher reimbursement per colonoscopy. This potential revenue increase can help fund the infrastructure to administer a large quantity of FIT tests to the community and create a truly equitable population-based approach to CRC screening. Methods: 27,169 colonoscopies and their associated CPT codes from 2017-2022 performed at TUH were analyzed. 16 individual CPT codes were identified and categorized as either screening or diagnostic CPT codes. Reimbursement for each of the CPT codes was determined by the Medicare reimbursement per CPT code and used to determine the average reimbursement per screening CPT code and average reimbursement per diagnostic CPT code. A Monte Carolo simulation model was created using Palisades @Risk software to compare the reimbursements of FIT test prompted vs. non-FIT test prompted colonoscopies over a range of possible distributions of diagnostic CPT codes. Monte Carlo simulations model scenarios that incorporate uncertainties with the objective of providing a distribution of outcomes from the least likely to most likely outcomes. Results: The historical distribution of screening vs. diagnostic CPT codes at TUH is 31% and 69%, respectively, with an average Medicare reimbursement of $2,668 per colonoscopy. We have distributed 292 FIT tests, and 5 FIT test prompted colonoscopies have been completed with 7 associated CPT codes. The preliminary distribution of screening CPT codes vs diagnostic CPT codes is 29% and 71%, respectively, with an average reimbursement of $2,691. Lastly, we used a Monte Carlo simulation to run 10 separate simulations with 5000 iterations each to show the most likely reimbursement rates over a possible distribution of diagnostic colonoscopies (Table). Conclusions: Our preliminary data suggests FIT testing can offer three main benefits: 1) Expansion of the number of patients receiving CRC screening; 2) triage optimization of the fixed capacity colonoscopy suite by performing more diagnostic colonoscopies than screening colonoscopies to diagnose more colorectal pathologies; and 3) funding for a population based FIT testing campaign by utilizing the Medicare reimbursement delta from screening to diagnostic colonoscopies. [Table: see text]
Effect of mail-in sperm cryopreservation solution on access to cryopreservation: A national demographic analysis.
Authors: Passarelli Rachel , Kenfield Stacey A , Nolte Daniel , Belarmino Andre , Civello Daniel , Smith James F , Velez Leitner Danielle
Published: May 2024

e13524

Background: There are many circumstances under which someone may choose to bank their sperm, but forthcoming cancer treatment is among the most common. The advent of services offering mail-in semen analysis and cryopreservation has expanded access to sperm banking, especially for those living in rural areas, far away from traditional andrology labs. This study summarized demographic characteristics and reasons for cryopreservation among those using one such US-based mail-in service, with a focus on patients banking sperm prior to cancer treatment. Methods: Patients >18 years who banked sperm using a mail-in cryopreservation solution developed by Fellow Health, Inc. from March 2021 to January 2024 were included. Test kits sold for research purposes were excluded. To categorize each patient by reason for cryopreservation, we made use of a patient-provided reason, supplied during test kit registration, where available. For the remaining patients, reason was inferred using several data sources including medical history, medications, and clinic and physician information. Patients who could not be reliably classified were omitted from this portion of the analysis. Descriptive statistics of key demographics and reason for cryopreservation were reported under an IRB-approved protocol. Results: 2,154 patients met our inclusion criteria and 725 (33.7%) provided demographic information. Average age was 34.7 (SD=9.2) years and 11.9% identified as a trans female. The majority of the population identified as white (79.5%) and non-Hispanic (84.8%). Over half of the population had a college degree or greater (59.3%), was married/partnered (57.1%), and had private insurance (84.9%). Among the 756 patients whose reason for cryopreservation was discernible, the majority, 450 (59.5%), were doing so in the context of fertility treatment, with only 46 (6.1%) indicating cancer treatment. Other reasons included pre-vasectomy storage (n=137, 18.4%) and gender affirming hormone therapy (n=90, 11.9%). Of the patients who indicated cancer treatment as their reason for cryopreservation, 50.0% lived greater than a 25-mile drive of the nearest National Cancer Institute (NCI)-designated Cancer Center. Conclusions: Surprisingly, few patients utilizing a mail-in service for cryopreservation did so prior to beginning cancer treatment, with most originating from the fertility or pre-vasectomy context. Use was disproportionately high among trans women initiating hormone replacement therapy (HRT), perhaps demonstrating their preference for at-home sample collection to avoid the unique challenges they encounter in a clinical setting. Especially for oncology patients who are admitted to a hospital and cannot leave for fertility preservation, there is an opportunity to further integrate mail-in cryopreservation services within oncology to improve access and reduce time costs.
Factors associated with delay in breast biopsy in a vulnerable population.
Authors: Sharma Shivani , Carrera Camila , Vasudevan Srivatsa Surya , Walker Nakoma , Martinez Shidestini Chanta , Chennapragada Suma Sri , Beedupalli Kavitha
Published: May 2024

e13526

Background: Prompt diagnosis and treatment of breast cancer can improve outcomes and reduce stress and anxiety in patients. Race, socioeconomic status, and education level are associated with delays in diagnosis in breast cancer patients. 63% of Louisiana’s parishes are classified as rural, and 18.8% of the population is below the poverty line (the second highest in the country). The above factors make access to care challenging. Our study aimed to identify factors associated with delay in breast biopsy after abnormal diagnostic imaging in our patient population. Methods: A retrospective cohort study including female patients >18 years undergoing breast biopsy for abnormal diagnostic imaging findings from 1/1/2022 to 12/31/2022 at LSU Health, Shreveport, was done. Patients with a prior history of breast cancer, pregnant females, and patients with cognitive defects were excluded. Patients were followed from abnormal diagnostic imaging to biopsy. Descriptive analysis was done for baseline cohort characteristics. Univariate and multivariate logistic regression models were used to find 95% Confidence Interval and Odds ratio (ORs) for independent factors associated with time to biopsy (TTB). The study was approved by IRB. Results: 148 women (mean age [SD]: 54 [12] years) were included in the analysis. 67.5% were African American, and 25.6% lived in rural areas. The mean distance from the patient’s home to our center was 26.7 miles (Range: 3-219). The mean TTB from abnormal diagnostic imaging was 13.79 days (Range: 0-84), and 67.5% of patients had TTB of =<14 days. A TTB of more than 14 days was considered a delay in biopsy. After adjusting for age, multivariate logistic regression showed rural residence was associated with TTB of >14 days. (OR: 2.5, 95% CI: 1.15-5.67, p=0.02) (Table). A distance more than 40 miles from the hospital was associated with a higher likelihood of TTB of >14 days on a multivariate model adjusted for age and race revealed (OR: 2.2, 95% CI: 1.004-5.10, p= 0.04). Conclusions: Patients residing in rural parishes and at a distance more than 40 miles from our center have a higher likelihood of delay in time to biopsy from the diagnostic imaging. Same-day breast biopsy should be prioritized in such patients to ensure timely diagnosis and treatment. Cancer Centers serving the safety net population can conduct similar studies and implement changes to ensure equitable access to care. [Table: see text]
Impact of a care delivery intervention for patients with socioeconomic disadvantages, in their preferred language of English or Spanish.
Authors: Khan Sarah , Weldon Christine B. , Trosman Julia R. , Valentine Tierra , Hernandez Jorge , PADURI SWETHA , Reddy Vijay Ketan , Sakhuja Anuradha , Czarnowski Daniel , Patel Twinkle , Oliveras Margarita , Ramirez Sandra , Williams Emilia , Valecha Gautam , Kassem Mohammed Azher , Sharma Jaya , Subramanian Seshan , Ravelo Arliene , Khosla Paramjeet Grewal
Published: May 2024

e13550

Background: Sinai Health System’s oncology program serves Chicago’s inner city patients with substantial needs for social and primary care, many of whom prefer communication in Spanish. Sinai has implemented a care delivery intervention to address these needs, using the 4R Oncology Model for patient-facing care planning and patient self-management. 4R (Right Info/Care/Patient/Time) has shown significant improvements in the timeliness of care cancer delivery and referrals to cancer care (1). Herein, we implemented the 4R intervention to improve the timeliness of care delivery and referrals to care, focusing on the social and primary care needs of Sinai patients. Methods: Evaluation was conducted by surveying historical control and intervention (4R) cohorts of patients in their preferred language of Spanish or English. The 4R cohort received care at a Sinai medical oncology clinic Apr 2023 - Jan 2024. Control cohort received care Jan 2023 – March 2023. Analyses were conducted using Fisher’s exact test. Results: Survey response: 76% (38/50) in control and 75% (33/44) in 4R cohorts. Participant characteristics were comparable between control and 4R cohorts, respectively: 55%, 58% Hispanic, 42%, 39% Black; 76%, 82% high school education or less; 87%, 97% < $30k annual income; 50%, 55% preferred Spanish; 47%, 45% preferred English. For the total cohorts, all 5 metrics improved between control and 4R, and 4 of the 5 metrics improved significantly (Table). Among Spanish-preferred patients, 3 of the 5 metrics improved significantly, while improvements among English-preferred patients were not statistically significant. Both language groups saw numerical, but not statistically significant improvement in receiving referrals to primary care and meeting all their practical and family needs. Conclusions: The 4R Oncology intervention resulted in significant improvement in time to treatment and referrals to social and primary care in our population of socioeconomically disadvantaged patients with high needs for these services. Patients preferring Spanish benefited at a higher rate than English-preferring patients, indicating that 4R may be an effective method to address the needs of this important patient group. Future efforts will further optimize 4R to address remaining gaps for this group, as well as to improve the delivery of this care for the English-preferred patients. 1. Trosman JCOOP 2021. [Table: see text]
Predicting persistent fever in patients with cancer using machine learning.
Authors: Sauer Christopher Martin , Brehmer Alexander , Rostalski Till , Schuler Martin H. , Nensa Felix , Reinhardt Hans Christian , Kleesiek Jens , Pucher Gernot
Published: May 2024

e13552

Background: Sepsis is the leading cause of hospital readmission and death in the developed world. Cancer patients are at high risk due to their underlying disease and therapies. Meanwhile, antimicrobial resistance increases steadily, warranting a more careful administration of antibiotics. Predicting fever persistence 48 hours after initiation of antibiotics could help reduce antibiotic escalation and chest CT scans in patients where fever is predicted to subside within the next 24 hours. Methods: All cancer patients of the University Hospital Essen (UHE) between 1/1/2020-7/1/2023, receiving broad-spectrum i.v. antibiotics, and having persistent fever after 48 hours of first administration were extracted from UHE’s Fast Health Interoperability Resources clinical database. Vital signs, clinically important covariates, as well as lag features of vital signs and laboratory values were included. The binary target to predict was prevalence of body temperature ≥38 °C after 48-72 hours. Gradient boosting machines, a deep learning neural network, logistic regression (LR), random forest (RF) and a voting ensemble classifier were implemented. Hyperparameter tuning and model validation was performed through five-fold stratified cross validation (80/20% train/test split). Results: Analyzing 2.9 million patient records of UHE we obtained approx. 27,000 hospitalized adults with cancer. Restriction to hematology/oncology wards and intravenous broad-spectrum antibiotics resulted in 1,267 cancer patients. Of these, 264 patients had persistent fever after 48 hours, of which 111 patients had solid cancers, 66 lymphomas, and 87 other hematologic malignancies. 72 hours after antibiotic therapy 160 patients (60.2%) had persistent fever. Based on the area under the precision-recall curve (AUPRC) of 81.7%, the voting classifier model had the highest predictive performance. The model shows a sensitivity of 85%, a specificity of 63%, a Negative Predictive Value (NPV) of 75% and a Positive Predictive Value (PPV) of 73% on a cross-validated test set (Table). Conclusions: Machine learning-based algorithms can predict fever evolution and assist in clinical decision-making, potentially contributing to better patient care by preventing unnecessary antibiotics escalations and CT scans. Based on current model performance, 25% of chest CT scans could be obsolete as patients will not have persistent fever after 48 hours. Additional results will be presented at the meeting. [Table: see text]