bluuebunny/crossref_metadata_2025 huggingface dataset:
The unexpected complications of the left bundle branch area pacing (LBBAP) maneuver: a case report
Authors: Park Soyoon , Choi Young , Oh Yong-Seog , Kim Sung-Hwan
Published: June 2024

Background

The lead of left bundle branch area pacing (LBBAP) inserted into the muscular septum will make the transvenous lead extraction (TLE) of LBBAP more challenging and because in LBBAP ventricular lead (V lead) should be inserted into the part of the septum, damage to the vessel near the lead could occur. The case reports introduced the complications of LBBAP previously introduced, but not being considered in detail.

Case presentation

The two patients (76-year-old man, 90-year-old man) with a complete atrioventricular block (CAVB) undergoing the LBBAP procedure experienced complications related to the procedure. The complications were abrupt dysfunction of V lead and damage to the septal vein in the process of the procedure, respectively. Fortunately, they were discharged without any other complications.

Conclusions

A deliberate approach for the procedure would be needed as well as successful insertion appropriate for the protocol of LBBAP. And long-term follow-up of complications should be needed.
On-treatment (tx) dynamic circulating tumor DNA changes (∆ctDNA) associated with progression-free survival (PFS) and overall survival (OS) of patients (pts) with HR+/HER2− advanced breast cancer (ABC) in MONALEESA-3 (ML-3).
Authors: Chia Stephen K. L. , Solovieff Nadia , Joshi Mukta , Im Seock-Ah , Bianchi Giulia Valeria , de la Cruz-Merino Luis , Jerusalem Guy Heinrich Maria , Sonke Gabe S. , Nusch Arnd , Beck J. Thaddeus , Slamon Dennis J. , Wang Craig , Zarate Juan Pablo , Su Fei , Neven Patrick
Published: June 2024

1012

Background: In ML-3, ribociclib (RIB) demonstrated a significant PFS/OS benefit over placebo (PBO) in pts with HR+/HER2− ABC. We report associations of on-tx ∆ctDNA with OS/PFS and tumor size and of ctDNA detectability with radiological progression. Methods: Pts were randomized 2:1 to RIB or PBO + fulvestrant as 1st- or 2nd-line tx. ctDNA levels were measured by NGS at cycle 1 day 1 (C1D1), C4D1, C8D1, and every 8 cycles until end of tx. Analyses included: Wilcoxon rank sum text to compare ∆ctDNA from C1D1 to C4D1; Kaplan-Meier method to visualize relationship of ctDNA with PFS/OS; Cox proportional hazards model for associations of ctDNA and tumor metrics (objective response rate, best % change, % change at 1st tumor evaluation); Fisher’s exact test to compare ctDNA detectability between arms; and ∆ctDNA across time points to assess lead time between ctDNA level-based and radiological progression. Results: Overall, 534/726 (73.6%) pts had paired C1/C4 measurements. Rates of detectable (+) and undetectable (−) ctDNA at C1 and C4 were: C1+/C4+, 33.0%; C1+/C4−, 34.5%; C1−/C4−, 27.5%; and C1−/C4+, 5.1%. RIB vs PBO had a larger % decrease in ctDNA level from C1 to C4 (P=0.003). Pts with better best overall response also had larger ctDNA decreases from C1 to C4 (P<0.0001). On-tx ∆ctDNA from C1 to C4 correlated with PFS/OS (P<0.0001; Table). C1-/C4-, C1+/C4-, and C1+/C4+ strongly correlated with PFS within response categories (PR, SD, NCRNPD). C1-to-C4 % ∆ctDNA was only moderately correlated with tumor size change (best % change, r=0.41; change at 1st evaluation, r=0.32; both P<0.001). Univariate/multivariate analyses showed significant correlations between ctDNA metrics (% change, detection pattern at C4D1) and PFS/OS. ctDNA detection and % change generally remained significantly associated with PFS/OS even after adjusting for change in tumor size. In a longitudinal analysis of pts who cleared ctDNA at C4D1 (C4–), the median lead time between ctDNA progression and radiological progression was 8.2 mo (IQR 4.5–15.6). Conclusions: On-tx ∆ctDNA from C1 to C4 was correlated with PFS/OS even after adjusting for tumor size changes, suggesting that ctDNA and tumor dynamics capture distinct aspects of tumor tx responses. Decreases in ctDNA were greater with RIB vs PBO, mirroring ML-3 efficacy readouts but at a much earlier timepoint. This longitudinal analysis of ctDNA in ML-3 suggests that detecting ∆ctDNA is a sensitive way to monitor progression and may be a potential surrogate for efficacy in HR+/HER2− ABC. Clinical trial information: NCT02422615 . [Table: see text]
Real world experience of trastuzumab deruxtecan for the treatment of metastatic breast cancer in the UK.
Authors: Cheng Andy , Frank Suzanne , Baines Katherine , Nathan Mark , Douglas Rosalie V. , Sylva Rushan , Ball Jessica , Savva Constantinos , Talbot Thomas , Oikonomidou Olga , Smith Jenny , Thomson Alastair , Ross Felicity , Konstantis Apostolos , Ainsworth Nicola , Luciano Pietro , Iyer Pooja , Acharige Shyamika , Rana Shaikh , King Judy
Published: June 2024

1024

Background: Trastuzumab deruxtecan (TDXd), an antibody drug conjugate, was first approved in the UK for the treatment of human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer (mBC) in 2021. We aimed to review the efficacy and tolerability of TDXd in a real-world UK setting. Methods: We collected clinical and demographic data from medical records on HER2+ mBC patients treated with TDXd in the UK from Jan 2021 to Dec 2023 inclusive. This included: radiological response, the frequency of dose reductions and treatment delays, and reasons for discontinuation. Clinical trial patients were excluded. Descriptive statistical techniques were applied. Results: Data was collected from 26 UK cancer centres on 280 patients. The median age at TDXd initiation was 56 years (range 29-85). Median treatment duration was 9 cycles (range 1-40). 239 patients (85%) had visceral disease. 257 and 196 patients (92% and 70%, respectively) had received prior Trastuzumab and Pertuzumab, respectively. 233 patients (83%) had received prior TDM1. The median number of lines of treatment prior to TDXd was 3 (range 1 to 9). 20 patients (7%) were initiated on a reduced dose and 115 further patients (41%) required at least one dose reduction. 151 patients (54%) had at least one dose interruption due to: infection or neutropenia (n=61), other toxicity (n=85), interstitial lung disease (ILD) investigation (n=39), patient request (n=81), other concurrent illness (n=10), and cardiac investigation (n=6). Of these, 55 patients had more than one treatment break. 157 patients (56%) had discontinued TDXd treatment due to: disease progression or death (n=100), drug toxicity (n=39) of which 22 were due to ILD, and patient choice (n=8). 123 patients remained treatment at the time of analysis. The overall response rate of TDXd was 63% overall: stable disease 23%, partial response 56%, complete response 7%. Conclusions: The real-world data set is not directly comparable to either the DB02 or DB03 trials, as it included patients who had received TDXd in both the second line and later line settings. However, the majority (80%) of these patients were treated in the third line and beyond. The rates of drug interruption and reduction were higher in the real-world data set than in DB02, which may impact on efficacy in the real-world setting. Overall response rate is similar between trial data and our real-world data, although the latter was not measured by RECIST. Data collection is ongoing, including an analysis of real-world progression free survival. [Table: see text]
Trastuzumab deruxtecan (T-DXd) vs trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Updated survival results of DESTINY-Breast03.
Authors: Hamilton Erika P. , Hurvitz Sara A. , Im Seock-Ah , Iwata Hiroji , Curigliano Giuseppe , Kim Sung-Bae , Chiu Joanne Wing-Yan , Pedrini Jose Luiz , Li Wei , Yonemori Kan , Bianchini Giampaolo , Loi Sherene , Santos Borges Giuliano , Wang Xian , Bachelot Thomas , Nakatani Shunsuke , Ashfaque Shahid , Liang Zhengkang , Egorov Anton , Cortes Javier
Published: June 2024

1025

Background: DESTINY-Breast03 (NCT03529110), a randomized, multicenter, open-label, phase 3 study, assessed the efficacy and safety of T-DXd vs T-DM1 in pts with HER2+ mBC treated with ≥1 prior anti-HER2 regimen. Median (m) overall survival (OS) was not reached in either arm at the prior data cutoff (DCO; Jul 25, 2022). We report updated survival results, including efficacy and safety, after median duration of follow-up of 41 mo. Methods: Pts were randomized 1:1 to T-DXd 5.4 mg/kg or T-DM1 3.6 mg/kg once every 3 weeks. Primary endpoint was progression-free survival (PFS) by blinded independent central review (assessed at prior DCO); key secondary endpoint was OS. Other secondary endpoints included objective response rate (ORR), PFS, duration of response (DoR), PFS from time of randomization to progression on next line of therapy or death (PFS2), and safety. All secondary endpoints were based on investigator assessment. Results: 524 pts were randomized (T-DXd, n = 261; T-DM1, n = 263). As of Nov 20, 2023, median duration of follow-up was 43.0 mo (range, 0.0-62.9) for T-DXd and 35.4 mo (range, 0.0-60.9) for T-DM1. mOS (95% CI) was 52.6 mo (48.7-not evaluable [NE]) for T-DXd and 42.7 mo (35.4-NE) for T-DM1 (hazard ratio [HR], 0.73), with 110 (42.1%) and 126 (47.9%) OS events, respectively. OS rate (95% CI) at 36 mo was 67.6% (61.3-73.0%; T-DXd) vs 55.7% (49.2-61.7%; T-DM1). mPFS was 29.0 mo for T-DXd and 7.2 mo for T-DM1; PFS rate (95% CI) at 24 mo was 55.8% (49.1-62.0%; T-DXd) vs 20.6% (15.4-26.4%; T-DM1). mPFS2 was 45.2 mo (T-DXd) vs 23.1 mo (T-DM1). Median treatment duration was 18.2 mo (range, 0.7-56.6) with T-DXd vs 6.9 mo (range, 0.7-55.2) with T-DM1; rates of treatment-emergent adverse events (TEAEs) were consistent with prior DCO. Adjudicated drug-related interstitial lung disease/pneumonitis occurred in 16.7% of pts with T-DXd (4 new events [all grade 2] since prior DCO) vs 3.4% with T-DM1 (1 new event [grade 1]); neither arm had grade 4 or 5 events. Key efficacy and safety results are shown in the table. Conclusions: The superiority of T-DXd over T-DM1 was reinforced in this long-term analysis, as observed by clinically meaningful improvement in OS, PFS, and PFS2, consistent with prior DCO. The safety profile of T-DXd continues to be manageable with no cumulative toxicities observed with longer follow-up. Clinical trial information: NCT03529110 . [Table: see text]
Survival outcome prediction of breast carcinomas on whole-slide histopathology images using deep learning.
Authors: Paul Julian , Bossard Céline , Rynkiewicz Joseph , Molinié Florence , Salhi Sanae , Frenel Jean-Sebastien , Salhi Yahia , Chetritt Jérôme
Published: June 2024

1070

Background: Breast cancer is the most common cancer among women with 2 million new cases and 627,000 deaths in 2020. Early diagnosis and effective treatment are crucial for improved outcomes. Prognosis mainly depends on histopathological features, among them grade. As whole slide histopathology image (WSI) of tumor tissue contains a huge amount of hidden morphological features unexploited by pathologists, we investigate the potential of Artificial Intelligence (AI)-based analysis on WSI to predict prognosis in terms of 5-year overall survival in breast cancer patients. Methods: We used a novel deep neural network (DNN), DiaDeepBreastPRS, designed specifically for predicting a survival risk score in breast cancer patients based on H&E-stained whole slide images (WSI) of tumor tissues. The model incorporates two distinct viewpoints, one capturing cellular details and the other the tissue-level information. DiaDeepBreastPRS was trained and evaluated on a multi-centric discovery cohort of 1,027 patients (1,095 H&E WSI) from the TCGA-BRCA dataset using a cross-testing and cross-validation technique. It was evaluated on an external cohort, comprising 232 patients (247 H&E WSI). A statistical analysis with a multivariate Cox regression model was carried out on clinico-pathological data. AI scores and the concordance index (c-index) serves as the metric for assessing the performance. The predicted risk scores were used for effective risk stratification of breast carcinomas. Results: On the TCGA-BRCA dataset, the model achieved an average c-index of 67%, which reaches 78% by adding the pTNM stage and age at diagnosis. On the external dataset, the model achieved a c-index of 66% and 75% when including some histopathological prognosis factors (pTNM stage, age at diagnosis, HER2 and HR status and mitosis). The AI score was independently associated with the survival of breast cancer patients with the highest hazard ratio (HR 2.46, p<0.005). Furthermore, the model was able to significantly discriminate between the 2 groups of patients, with a good and a poor prognosis in terms of overall survival (p<0.005). Conclusions: In this study, we showcased that the algorithm was able to instantly extract prognostic morphological features from H&E whole slide images (WSI) and could be included in the pathology report. This could potentially enhance clinical decision-making, elevating the standard of care. Compared to commonly used molecular signatures, the AI algorithm enables a reduction in response time and cost savings. However, further investigations using additional independent cohorts are essential to consolidate the algorithm's performance and allow its generalizability, establish its superiority over existing prognostic markers, and provide insights into its interpretability.
Real-world (RW) elacestrant use patterns and therapeutic outcomes in patients (pts) with hormone receptor-positive (HR+)/HER2-negative advanced breast cancer (aBC).
Authors: Lloyd Maxwell Roger , Ali Azka , Weipert Caroline M. , Solomon Sheila R , Saha Jayati , Lipsyc-Sharf Marla , Hamilton Erika P. , Kalinsky Kevin , Bardia Aditya , Zhang Nicole , Wander Seth Andrew
Published: June 2024

1071

Background: Elacestrant was the first novel endocrine therapy (ET) to receive FDA approval in over two decades. In the EMERALD study, pts with ESR1-mutant ( ESR1m) HR+/HER2-negative aBC had a median progression free survival (PFS) of 3.8 months (mos). Here, we use a large clinical-genomic database to assess the RW use of elacestrant and examine the impact of line of therapy (LOT) and number of ERS1m on pt outcomes. Methods: Pts with HR+/HER2- aBC were identified via the GuardantINFORM database; all pts with ESR1m detected on circulating tumor DNA (ctDNA) testing done in routine clinical care and treated with elacestrant after the FDA approval date were included. Real-world time to treatment discontinuation (TTD) and time to next treatment (TTNT) were used as proxies for PFS (measured in mos). For TTD/TTNT, Kaplan-Meier curves and median time-to-event with 95% confidence intervals (CI) were used. For outcomes specific to single versus >1 ESR1m, only pts with an ESR1m detected within the 6 months prior to elacestrant start were included. Results: 418 aBC pts were treated with elacestrant, with a median age of 62 years. Elacestrant was used across metastatic LOT (2nd: 12%, 3rd: 18%, 4tH: 17%, 5th+: 53%). Considering all prior therapies, pts commonly received prior aromatase inhibitors (AI) (89%), CDK4/6i (73%), fulvestrant (63%), and chemotherapy (49%). Of 312 pts with testing within 6 months of elacestrant start, 56% harbored a single ESR1m, with a maximum of 11 ESR1m detected in a single patient. TTD was 5.4 mos (95% CI: 4.2 - not reached [NR]) and TTNT was 6.2 mos (95% CI: 5.7 - NR); most pts were censored at the time of analysis (65% for TTD, 71% for TTNT). There were no significant differences in TTD or TTNT based on number of prior LOT or number of ESR1m mutations (Table 1). Data was not yet mature to assess differences in outcomes based on prior ET use, duration of prior CDK4/6i exposure, specific ESR1m, or co-occurring alterations. Conclusions: Using a clinical-genomic database, we present early RW insights of aBC pts treated with elacestrant. Initial outcomes, as assessed via TTD and TTNT, exceed the PFS reported in the EMERALD trial, perhaps due to multiple factors impacting patient selection and restaging protocols, which can differ in prospective trials versus routine clinical care. Factors such as prior LOT and number of ESR1m did not impact patient outcomes; additional factors such as prior ET use, duration of CDK4/6i treatment, specific ESR1m, and co-occurring mutations will be assessed as data matures. [Table: see text]
Impact of use of antibody drug conjugates on the prognostic outcome of patients with HR+ve/HER2-ve MBC: Results from a real world dataset.
Authors: Dawood Shaheenah S. , Hernández Gema , Segovia Alba
Published: June 2024

1076

Background: Two antibody drug conjugates trastuzumab deruxtecan (T-DXd - in the HER2 low cohort) and sacituzumab govitecan (SG) have been shown to improve both PFS and OS among pts with HER-ve MBC. The objective of this retrospective analysis was to look at trends in the use of and associated prognostic outcome associated with T-DXd and SG among pts with HR+ve/HER2-ve MBC in the real-world setting. Methods: We utilized a federated network of de-identified health data representing approximately 107 million pt lives available through the TriNetX Research Network. We identified pts with HR+ve/HER2-ve MBC diagnosed between Jan 2004 and Jan 2024. Propensity score matching analysis by age, site of metastases and chemotherapy was carried. OS was computed using the Kaplan Meier product limit method. Results: 17,133 pts with HR+ve/HER2-ve MBC treated with endocrine therapy and CDK4/6i were identified of whom 249 pts (1.45%) and 162 pts (0.94%) received SG and T-DXd respectively. 32 pts (0.19%) received T-DXd + SG. Median time from diagnosis of MBC to start of SG and T-DXd was 625 days and 233 days respectively. 5-yr OS for the whole cohort was 58.1%. 5-yr OS among pts who did and did not receive T-DXd was 74.8% and 52.2% respectively (HR 0.44, 95% CI 0.28 - 0.69; p = 0.0002). 5-yr OS among pts who did and did not receive SG was 73.4% and 64.7% respectively (HR 0.62 95% CI 0.42 - 0.90, p=0.012). 5-yr OS among pts who did and did not receive T-DXd + SG was 77.4% and 62.4% respectively (HR 0.55, 95% CI 0.19 - 1.59, p=0.26). 5-yr OS was 68.1% and 74.5% among pts who had received SG alone or T-DXd alone respectively (HR 1.31, 95% CI 0.84 - 2.03, p =0.22). Conclusions: In a real-world data set we report on the OS benefit associated with the use of SG and/or T-DXd at some time point in the therapy of pts with HR+ve/HER2-ve breast cancer who have progressed on endocrine therapy and CDK4/6i.
Utility of axillary surgery in patients with de novo metastatic breast cancer undergoing surgery of the primary site.
Authors: Vasigh Mahtab , Ruth Karen J , Bleicher Richard J. , Aggon Allison A. , Pronovost Mary , Porpiglia Andrea S , Williams Austin D.
Published: June 2024

1086

Background: Approximately 6% of patients have de novo metastatic breast cancer (MBC) for whom surgery is reserved for special circumstances since it confers no survival benefit. The prospective studies evaluating surgery of the primary site in MBC recommended standard surgical management of the axilla. However, it is unclear whether axillary surgery is of any utility among these patients. We sought to evaluate the survival benefit of axillary surgery in MBC patients undergoing primary site surgery. Methods: From the National Cancer Database (2012-2020), we identified patients aged 18-79 with MBC undergoing surgery of the primary site and grouped patients according to axillary surgery performed: none, sentinel lymphadenectomy (SLNB), or axillary lymph node dissection (ALND) with or without SLNB. We performed a landmark analysis beginning 12 months after diagnosis to assess overall survival (OS) and used Cox regression to adjust for clinicodemographic characteristics. Results: We identified 7,808 patients, 20.2% of whom had no axillary surgery, 16.3% had SLNB, and 63.5% had ALND. Of the patients who had axillary surgery, 26.3% were pN0. Patients who had no axillary surgery, were older (mean 57.2 vs 60.3 years), more likely to have tumor histology other than ductal or lobular (8% vs. 4%), be cN0 (28% vs. 20%), less likely to have bone-only metastases (36% vs. 44%) and undergo breast-conserving surgery (49% vs. 24%) [all p<0.001]. The mean and median number of positive nodes was 1.3±2.3 in the SLNB, and 5.9±6.8 in the ALND group. 36-month adjusted survival estimates were 71.4%, 66.5%, and 58.0% for SLNB, ALND, and no axillary surgery groups, respectively. On univariate analysis and after adjusting for clinicodemographic features, both SLNB and ALND remained independently associated with improved OS when compared with no surgery (Table). Conclusions: As in prior retrospective analyses of surgery for the primary site, we found that the performance of axillary surgery in MBC patients was associated with improved OS. Selection bias is likely a contributing factor as surgeons are more likely to recommend axillary surgery for patients with a better functional status. Of concern is the number of MBC patients being exposed to the morbidity of ALND who are ultimately pN0, and thus derived no benefit. These findings highlight the need to carefully weigh the risks and benefits before performing axillary surgery. Prospective studies evaluating axillary surgery are needed to validate these results. [Table: see text]
SV-BR-1-GM after progression on ADC in patients with metastatic breast cancer.
Authors: Nangia Chaitali Singh , Calfa Carmen Julia , Bayer Blaise , Chang Mingjin , Aghajanian Tamar , Williams William , Del Priore Giuseppe , Wiseman Charles L. , Chumsri Saranya
Published: June 2024

1087

Background: Antibody-drug conjugate (ADC) sequencing raises concerns of cross-resistance due to their shared targets and cytotoxic payloads. Consequently, treatments after ADCs in heavily pretreated MBC is uncertain. SV-BR-1-GM, a GM-CSF secreting, antigen-presenting immortalized breast cancer cell line, has emerged as a post ADC solution (1) based on a different MOA. We now report the results of SV-BR-1-GM in ADC treated patients. Methods: Post-hoc analysis of an ongoing randomized Phase 2 censored to the data-cut date prior to data lock. Bria-IMT (~20x106 SV-BR-1-GM cells, intradermally 48-72 hours after ctx (300 mg/m2), followed by interferon-alpha 2 days later) administered q3wks with a checkpoint inhibitor (CPI). Adverse events were classified according to their severity and relationship to treatment regimen. Results: Among 54 advanced MBC patients randomized, 23 who failed prior ADC therapy were identified. All were heavily pretreated (median 6 prior lines, range 3 – 13). Median age 62 (41-83). 14 pts had HR+/HER2-, 5 TNBC, and 2 HR+/HER2+ MBC. The remaining were HR-/HER2+ or HR-/HER2 low. 8 pts received > 1 ADC. Prior ADCs included: 4 ado-trastuzumab emtansine, 14 trastuzumab deruxtecan, 13 sacituzumab govitecan. 7 pts had also received ≥ 1 prior CPI line. To date, pts received a median 3 cycles of Bria-IMT™ + CPI (2-8). Kaplan-Meier analysis revealed a median OS of 42 weeks with survival of 69% at 6 months. The subset experienced a median PFS of 74 days with 40% of pts demonstrating a Bria-IMT PFS (PFS2) similar to or > their prior line PFS (PFS1). 39% of pts experienced a PFS2 ≥ their most recent line of ADC PFS. The disease control rate was 40% among evaluable pts. 43% of pts had a reduction in cancer-associated macrophage-like cell (CAML) levels; median reduction was 36% (22-98%) after 1 cycle. There were no toxicity-related treatment discontinuations. 43% (10/23) reported grade 3 or 4 AEs, independent of study drug causality. AEs included injection site reaction (39%), fatigue (26%), and nausea/vomiting (43%), mostly mild to moderate. One case of elevated lipase was the most clinically significant grade 4 AE. No interstitial lung disease (ILD) was reported. Conclusions: This subset analysis of the Bria-IMT regimen in ADC refractory MBC patients suggests a potential clinical benefit and treatment option for this patient population. The absence of serious AEs, notably interstitial lung disease (ILD), and no toxicity-related treatment discontinuations, underscores the regimen's favorable safety profile. Future studies are warranted to confirm these results and explore the potential of Bria-IMT™ in broad clinical settings of heavily pretreated contemporary MBC patients. 1. Kamaraju 2024 AACR. Clinical trial information: NCT03328026 .
Racial disparities among triple negative breast cancer clinical trial enrollees between 2010-2023.
Authors: Rao Divya , Brabant Paige , Chau Isabelle , Darrell Megan , Yao Chi-Yen , Roth Melanie , Pandit Maya , Gary Monique , Etienne Mill
Published: June 2024

1093

Background: Despite the social construct of race lacking biological significance, it plays a significant role in health disparities and necessitates examination to address social stratification and health inequities. Not reporting race in medical research neglects the reality of social stratification, injustices, and implications for population health. Additionally, excluding racial demographic data from research publications may conceal health disparities. This study focuses on Triple Negative Breast Cancer (TNBC) clinical trials, aiming to meta-analyze the inclusion of racial data and assess racial representation. Methods: A meta-analysis of 81 completed TNBC trials (2011-2023) from ClinicalTrials.gov was conducted. Demographic data on race and sex were extracted and analyzed using Microsoft Excel. Two independent reviewers extracted study-level data for a random-effects analysis. The primary outcome was identifying the prevalence of studies lacking racial data. The secondary outcomes are the prevalence of each racial category (White, Black, Asian, Hispanic/Latino, and Combined Other) among all TNBC clinical trials that reported demographic information. The Combined Other category includes American Indian, Native Hawaiian, more than one race, and unknown/unreported. Results: Of 81 trials, 29.63% did not report racial data. The remaining 57 trials (8,196 participants) revealed 73.98% White, 10.29% Asian, 7.85% Black, 8.02% Hispanic/Latino, and 4.12% "combined other" participants. U.S.-based trials (36 studies, 3,348 participants) showed 77.96% White, 12.03% Black, 4.51% Asian, and 4.96% Hispanic/Latino participants. Moreover, we conducted a comparative analysis between the racial distribution in U.S. clinical trials and the prevalence of TNBC in the U.S. population, utilizing the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Public Use Datasets (2010-2019). The analysis revealed a significant discrepancy with White (p<.001) participants being overrepresented, and Black (p<.001), Asian (p<.001), Hispanic/Latino (p<.001), American Indian (p<.001), more than one race (p<.02), and Other/Unknown (p<.001) populations being underrepresented. Conclusions: Globally, 29.63% of TNBC trials did not report racial data, raising concerns about generalizability. U.S.-based studies exhibited overrepresentation of White participants and underrepresentation of Black, Asian, Hispanic/Latino, American Indian, Native Hawaiian, and other categories. Notably, Black and Hispanic/Latino individuals, comprising a substantial portion of TNBC patients, were underrepresented. These findings underscore racial/ethnic disparities in breast cancer trial participation, warranting further investigation into recruitment barriers for equitable participation.
Current management practices of de novo oligometastatic breast cancer: Real-world data from a physician survey.
Authors: Odzer Nicole , Pusztai Lajos , Rozenblit Mariya
Published: June 2024

1104

Background: De novo oligometastatic breast cancer (oligo-mBC) is generally defined as < 5 lesions at the time of diagnosis and represent a steadily increasing subset of metastatic cancers. Several retrospective studies demonstrated prolonged overall survival (OS) for select patients with oligo-mBC when treated with multimodality therapy (chemotherapy, surgery, and radiation). However, randomized trials that tested surgical resection of the primary tumor, or radiation of oligometastases (including recurrent and de novo disease) showed no OS benefit. No randomized trials to date have tested all 3 treatment modalities combined (as used with curative intent in early-stage disease). Current NCCN guidelines do not include specific recommendations for de novo oligo-mBC, the St Gallen International guidelines allow multimodality therapy for carefully selected patients. We surveyed practicing medical oncologists through the ASCO survey pool regarding their use of multimodality therapy in de novo oligo-mBC. Methods: An online survey was sent to the ASCO Research survey pool (N=999) between 11/14/23 – 12/29/23, 193 ASCO members completed the survey. Data was confidential and anonymous. Results: The majority (76-79%) of respondents recommend starting with palliative systemic chemotherapy. If patients have a response to initial chemotherapy, 42-54% recommend ablative radiation to all residual lesions, and 38-52% recommended surgical resection of the primary tumor. Overall, multimodality therapy is recommended sometimes by 29-36%, often by 19-29%, almost never by 32-41%, and never by 2-7% of respondents. Recommendations varied by disease subtype (Table). Conclusions: These survey data indicate varied practices in the treatment of de novo oligo-mBC. This highlights the need for future randomized clinical trials to investigate whether there may be survival benefit by receptor subtype in de novo oligo-mBC treated with curative intent multimodality therapy as used in locally advanced cancers. [Table: see text]
Harmonization radiomics model to predict immune checkpoint inhibitor-related pneumonitis (CIP) in patients with non-small cell lung cancer (NSCLC).
Authors: Yadav Monica , Lee Jeeyeon , Kim Haseok , Lee Seyoung , Um Taegyu , Lee Salie , Djunadi Trie Arni , Chung Liam IL Young , Yu Jisang , Rodrigues Darren , Gennaro Nicolo , Kim Leeseul , Kim Yuchan , Nam Myungwoo , Hong Ilene , Jang Jessica , Cho Amy , Kang Grace , Velichko Yury , Chae Young Kwang
Published: June 2024

12142

Background: The increasing use of immunotherapy in advanced non-small cell lung cancer (NSCLC) presents a significant challenge in managing adverse events, particularly checkpoint inhibitor-associated pneumonitis (CIP). This potentially life-threatening complication often necessitates discontinuation of immunotherapy, even in patients experiencing tumor response. Presently, there are no reliable models to predict the onset of CIP. This research utilizes CT radiomics to create an innovative approach for anticipating the risk of CIP in patients with NSCLC. Methods: This IRB-approved, retrospective study analyzed data from 159 stage III-IV NSCLC patients undergoing immunotherapy. We categorized patients into pneumonitis (further subdivided into immunotherapy-induced, radiation-induced, and others) and non-pneumonitis groups. Using LIFEx software, we extracted 3D-radiomic features from both tumors and surrounding 1cm thick peritumoral regions. To address scanner-associated variations, a linear mixed-effect radiomics harmonization model was applied. A Random Forest algorithm was then used to develop a classification model predicting CIP occurrence based on the pre-treatment CT radiomic and clinical data. The dataset was split into training (70%) and test (30%) sets. The accuracy of predictions was evaluated using confusion matrix statistics and bootstrapping with 1,000 iterations for median and 95% confidence interval (CI). The performance metrics included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the ROC curve (AUC). Results: 159 patients were analyzed, of which only 19 had checkpoint inhibitor-related pneumonitis. Among which, 17 (54.8%) patients had grade 1 pneumonitis, 12 (38.7%) patients had grade 2 pneumonitis, 2 (6.5%) patients had grade 3 pneumonitis, and none had grade 4 or grade 5 pneumonitis. The model achieved a sensitivity of 0.98 (0.97, 0.99), a specificity of 0.08 (0.05, 0.14), a PPV of 0.91 (0.90, 0.91), and an NPV of 0.33 ± 0.23 for predicting CIP. The AUC of 0.59 (0.56, 0.66) indicates that the model may predict checkpoint inhibitor-associated pneumonitis with an accuracy of 59%. Conclusions: The study provides insights into the potential of radiomic analysis coupled with AI algorithms and the use of harmonization model in predicting CIP among NSCLC patients treated with immunotherapy. However, larger studies are needed to validate our findings and the utility of harmonization models in predicting CIP.
Using machine learning for targeted advance care planning (ACP) conversations in patients with cancer: A quality improvement initiative.
Authors: Patel Mihir , Mara Alexandria , Acker Yvonne , Gollon Jamie , Wolf Steven , Zafar Yousuf , LeBlanc Thomas William , Ma Jessica
Published: June 2024

1552

Background: Despite improvements, patients with advanced cancer often do not receive goal-concordant care at the end of life (EOL). Challenges with prognostication contribute to delays ACP conversations and result in more aggressive care, gaps in symptom management, and hospice underuse. Early identification of patients at high risk for mortality provides an avenue to implement targeted ACP conversations. Methods: We used a validated machine learning model that integrates demographics, lab values, vital signs, and medications to predict in-hospital, 30-day, and 6-month mortality risk for patients with a solid malignancy admitted from the emergency department (ED) to a dedicated solid malignancy oncology unit at Duke University Hospital. This unit includes one oncology and one palliative care attending physician, advance practice providers, and nurse coordinators. Providers received an email when a patient was identified as high risk for mortality. A pre-post study design compared ACP documentation and other EOL healthcare utilization before and after the notification intervention. The pre-intervention cohort included patients hospitalized from 1/7/2019 to 10/25/2019 and the post-intervention cohort from 9/19/2020 to 8/31/2021. We excluded patients admitted to the intensive care unit in the first 24 hours. We used chi-square or Fisher’s exact tests for categorical variables and Kruskal-Wallis tests for continuous variables; we stratified comparisons of categorical variables by physician division using Cochran-Mantel-Haenszel tests. Results: The pre-intervention cohort comprised 105 hospitalizations and 88 unique patients. Mean (SD) age was 64.9 (11.4); 60.0% (n=63) were White, 3.8% (4) Hispanic/Latino, and 65.7% (69) married. The post-intervention cohort comprised 84 hospitalizations and 77 patients. Mean (SD) age was 66.0 (12.2); 52.4% (44) were White, 2.4% (2) Hispanic/Latino, and 60.7% (51) married. Considering index hospitalizations, an ACP note was written for 2.3% (2) of hospitalizations pre-intervention vs. 80.5% (62) post-intervention (p <0.0001). This relationship held even if the physician was in palliative care (4.1% [2] vs. 84.6% [33]) or oncology (0% [0] vs. 76.3% [29]) (p <0.0001). Inpatient length of stay (LOS), hospice referral, code status change, ICU admission rate or LOS, 30-day readmissions, 30-day ED visits, and inpatient and 30-day deaths did not differ significantly between groups. Conclusions: Identification of hospitalized cancer patients with high mortality risk via machine learning led to a substantial increase in documented ACP conversations but did not impact EOL healthcare utilization. Further integration of the model in clinical practice is ongoing. Our intervention showed promise in changing clinician behavior, and additional work is needed to evaluate downstream impacts.
Performance of an artificial intelligence/machine learning model designed to identify hospitalized patients with cancer who could benefit from timely specialized palliative care delivery.
Authors: Strand Jacob J. , Morgan Alisha A , Pachman Deirdre R. , Storlie Curt B , Wilson Patrick M
Published: June 2024

1559

Background: Timely access to specialty Palliative Care (SPC) services provides significant benefits to hospitalized patients with cancer, including improvements in quality of life. However, many patients with cancer who could benefit from SPC suffer from lack of timely referral or do not receive SPC services. A previously published trial of an artificial intelligence/machine learning (AI/ML) model to predict need for SPC at Mayo Clinic increased timely SPC consultation of hospitalized patients overall. We sought to review the performance of this algorithm in patients with cancer across an expanded hospitalized population. Methods: The study population consisted of all patients admitted into a Mayo Clinic hospital in Minnesota, Wisconsin, Arizona and Florida between January 2020 and September 2023. Due to the size of the cohort a case-control sample of three controls for every case was created. Patients were considered to be a patient with cancer if they had at least one billing diagnosis up to 1 year prior to their index hospitalization from any of the 5 HCC categories denoting cancer: Metastatic Cancer and Acute Leukemia (HCC 8); Lung and Other Severe Cancers (HCC 9); Lymphoma and Other Cancers (HCC 10); Colorectal, Bladder, and Other Cancers (HCC 11); and Breast, Prostate, and Other Cancers and Tumors (HCC 12). The training data set consisted of 107,076 patient encounters with a total of 8,355,090 time periods of constant risk. An AI/ML model using gradient boosting methods which contained 269 variables (both static and time-varying) of various classes with SPC consultation treated as a time-to-event outcome was trained. Results: Due to the longitudinal nature of the prediction, performance was assessed using the max score AUC (using the max score a patient received during a given encounter prior to an event or discharge) to produce the AUC. The model had an overall AUC of 0.932 (0.929, 0.935 – 95% CI). We saw a decrease in performance of the AI/ML model in the Oncology population with an overall performance of 0.818 (0.806, 0.83). Some of the most influential variables were previous SPC visit, age, metastatic disease, acute leukemia diagnosis, and pain scores. Conclusions: An AI/ML model can effectively predict the need for an inpatient PC consult in a population of hospitalized patients with cancer. [Table: see text]
Real world study of racial disparities associated with toxicities of sacituzumab govitecan.
Authors: Priyadarshini Shista , Petucci Justin , Katoch Avnish , Honavar Vasant , Vasekar Monali K.
Published: June 2024

1572

Background: Sacituzumab govitecan (SG) is approved in the treatment of metastatic hormone receptor positive and triple negative breast cancer (BC). The efficacy of SG across racial subgroups is known but no real-world data compares the racial differences in toxicities. We aim to expand knowledge about racial disparities regarding SG toxicities and any ineffective treatment or drug failure. Methods: We utilized TriNetX, a multi-health care organization electronic health record database, to identify African American (AA) and Caucasian (C) cohort for outcome comparison. Inclusion criteria required a C50 ICD-10-CM diagnosis code and at least one SG treatment. Age, gender, and race-controlled Cox proportional-hazard (CPH) model was used to analyze the time until the first pause or cessation of SG (defined as first deviation from the approved 21-day SG cycle). Several measures of deviation were noted 0, ±1 and ±3 days. Association between race and toxicity outcomes (controlled for age and gender) for anemia, neutropenia, thrombocytopenia, nausea and inpatient encounters were evaluated using multiple logistic regression (MLR). The odds (OR) and hazard (HR) ratios with corrected p-values are reported as an effect size and significance estimation. Results: 823 patients met the inclusion criteria (545 C, 116 AA & 162 unknown). The mean age (in years) at the initiation of 1st SG treatment was 58.22 ± 12.7 for C and 58.19 ± 12.18 for AA. AA had a 1.26 times higher hazard of SG treatment pause/cessation as compared to C. Blacks experienced an 88% increase in the odds of having a delay longer than 7-days between 2 doses of 1st cycle SG. Males were found to have an 80% increase in the pause/cessation rate as compared to females. The median number of SG treatments was 6 (3 cycles) for both AA and C. SG was noted as 4th chemo line (median) among all races. When compared to C, AA had decreased odds for neutropenia, increased odds for anemia and increased odds for hospitalization. Hazard Ratio and corrected p-values for outcomes comparing the AA and C cohorts. Conclusions: Survival analysis indicates that AA and male patients have an increased SG treatment pause/cessation rate. While the result is sensitive to specific conditions used to calculate the deviation, an increased odds of delay in treatment is also found using logistic regression modeling. Additionally, AA experience increased odds for anemia and late-stage hospitalization. These findings highlight the impact of race on BC outcomes, treatment toxicities and the need for further research to enhance treatment outcomes in diverse populations. [Table: see text]
Re-irradiation in recurrent glioblastoma: PET- or MRI-based? Results of a prospective randomized clinical trial.
Authors: Popp Ilinca , Weber Wolfgang A. , Graf Erika , Mix Michael , Wiehle Rolf , Nestle Ursula , Schimek-Jasch Tanja , Niyazi Maximilian , Belka Claus , Paulsen Frank , Eckert Franziska , Eble Michael J. , König Liane , Giordano Frank Anton , Sperk Elena , Momm Felix , Spehl Irina , Combs Stephanie E. , Bernhardt Denise , Grosu Anca L. ,   GLIAA Study Group
Published: June 2024

2021

Background: Re-irradiation is an important treatment option for recurrent glioblastoma (rGBM). Here, we aimed to compare the oncological outcome of a re-irradiation target volume delineation based on O-(2-[18F]fluoroethyl)-L-tyrosine (FET) positron emission tomography (PET) with the one of a treatment based on contrast enhanced T1-weighted magnetic resonance imaging (T1Gd-MRI). Methods: GLIAA was a prospective, multicenter, randomized trial (NOA 10/ARO 2013-1, DKTK-a.). Patients with rGBM recurrence of 1-6 cm following initial radiotherapy were recruited at 14 centers in Germany and randomized 1:1 between a FET-PET- (arm A) and a T1Gd-MRI-based target volume delineation (arm B). The treatment consisted in a high-precision stereotactic re-irradiation with 39 Gy in 13 fractions. The primary endpoint was progression-free survival (PFS) from randomization. Secondary endpoints included overall survival (OS), local tumor control, and toxicity. Results: From November 26, 2013, to September 2, 2021, 271 patients were assessed for eligibility and 200 were randomized. 98 patients in the FET-PET arm and 97 patients in the T1Gd-MRI arm were treated per protocol. Median PFS was 4.0 months (95% confidence interval [CI] 3.7-5.2) in the FET-PET arm and 4.9 months (95% CI 3.7-6.0) in the GdT1-MRI arm (one-sided stratified log-rank test p=0.98; adjusted HR for the experimental versus the control arm 1.14 [95% CI 0.85-1.52], p=0.39). Median OS was 9.4 months (95% CI 7.8-11.1) in arm A and 9.0 months (95% CI 7.6-10.5) in arm B (HR 1.01 [95% CI 0.75-1.37], p=0.92). Local control rate at 12 months was 22% in the FET-PET arm (95% CI 14%-31%) and 20% in the GdT1-MRI arm (95% CI 12%-29%). Radiation necrosis as adverse event was documented in 25.5% of cases in arm A and in 21.6% in arm B. Of the 239 patients who received the FET tracer, 3 reported 5 severe adverse events in the timespan of 7 days after PET. No event was related to the application of the tracer. Conclusions: In this trial, FET-PET-based re-irradiation of rGBM was not superior to the GdT1-MRI-based treatment. Consequently, both options remain valid in this setting. Stereotactic re-irradiation with 39 Gy in 3 Gy fractions was shown to be safe and the FET-PET investigation was well tolerated in all cases. Due to the inclusion of FET-PET-positive patients only, our results do not impact the known diagnostic role of FET-PET in differentiating rGBM progression from post-therapeutic changes. Clinical trial information: NCT01252459 .
Genomic biomarkers of CNS-specific outcomes in patients with breast cancer brain metastases.
Authors: Khatri Ishaani S. , Eichholz Jordan , Boe Lillian A , Safonov Anton , Smith Deborah Ruth , Ferraro Emanuela , Shen Junchao , Imber Brandon S. , Yu Yao , Yamada Yoshiya , Miao Emily , Moss Nelson S. , Wilcox Jessica , Walch Henry S. , Chatila Walid Khaled , Schultz Nikolaus , Razavi Pedram , Pike Luke R. G.
Published: June 2024

2028

Background: The diagnosis of brain metastasis (BM) is a life- and prognosis-altering event for patients with breast cancer (BC). The standard of care for the management of limited BM remains ablation with stereotactic radiosurgery (SRS). There are no established genomic biomarkers to guide CNS-directed treatment among patients with breast cancer brain metastases (BCBM). Methods: We retrospectively reviewed clinical and genomic features of a cohort of patients who received SRS for newly diagnosed BCBM between 2010 and 2021 at Memorial Sloan Kettering Cancer Center (MSK). Next-generation genomic sequencing (NGS) was performed using the MSK-IMPACT assay, covering all exonic and selected intronic regions for up to 505 genes. Time-to-CNS progression (TTCP) and overall survival (OS) were analyzed using multivariable Fine-Gray and Cox proportional hazards models, respectively, adjusted for clinically relevant factors. Relevant clinical factors and genomic alterations present at an instance at 5% or greater were included in the univariate and multivariate analyses, completed for the overall cohort and BC receptor subtypes. Results: From 2010-2021, 260 patients were identified; 123 (47%), 74 (28%), and 63 (24%) patients had hormone receptor-positive (HR+), HER2+, and triple-negative (TN) disease, respectively. 116 (45%) patients had 1 BM and 184 (71%) patients had at least 1 BM greater than 1 cm in axial diameter. Median follow up for the overall cohort was 18 months (Interquartile range (IQR) 9, 36). Among patients who progressed, median TTCP was 6 (IQR 4, 13) and 6 (4, 13), 11 (5, 18), and 4(3, 8) months for the overall cohort, and HR+, HER2+, and TN subgroups, respectively. Median OS was 19 (95% CI 16, 23) and 15 (13, 21), 58 (39, --), and 13 (11, 20), for the overall cohort, and HR+, HER2+, and TN subgroups, respectively. In the overall cohort, shorter TTCP was associated with TN subtype, >5 BMs, and pathogenic alterations in MYC, AGO2, PTEN, AURKA, and NF1 (p < 0.05); decreased OS was associated with non-HER2+ subtype, presence of extracranial metastatic disease, and oncogenic alterations in TP53, CDH1 and NF1 (p < 0.05). In stratified analyses by receptor subtype, shorter TTCP was associated with oncogenic alterations in GAB2 and PTEN in the HR+ subgroup, AURKA, DDR2, and NF1 in the HER2+ subgroup, and with MYC and RB1 in the TN subgroup (p < 0.05). Conclusions: In this large clinico-genomic analysis of CNS-specific outcomes in BC, we identified clinical and putative genomic biomarkers associated with BCBM receiving SRS that could be used to risk stratify patients and optimize treatment strategies.