bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and safety of irinotecan-eluting HepaSphere transarterial chemoembolization combined with hepatic arterial infusion chemotherapy for unresectable colorectal liver metastases.
Authors: Feng Aiwei , Gao Song , Guo Jianhai , Kou Fuxin , Liu Shaoxing , Zhang Xin , Liu Baojiang , Wang Xiaodong , Chen Hui , Xu Haifeng , Liu Peng , Cao Guang , Gao Qinzong , Zhu Xu 
Published: June 2023

3585 Background: Both drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) are recommended for unresectable colorectal liver metastases (CRLM) treatment. However, the combined application of DEB-TACE and HAIC is not widely accepted. The aim of this single-center retrospective study was to evaluate the efficacy and safety of Irinotecan-eluting HepaSphere chemoembolization combined with HAIC for unresectable CRLM. Methods: Patients with age older than 18 years, histologically confirmed CRLM and treated with Irinotecan-eluting HepaSphere chemoembolization plus HAIC from Oct 2020 to Jan 2022 were enrolled. Patients who had synchronously received other local treatments were excluded. Hepatic progression-free survival (hPFS) and PFS were calculated using Kaplan-Meier method. Adverse events (AE) were evaluated with CTCAE 5.0. Results: The eligible population was 101, composed of 66 males and 35 females. Among them, 54% patients had one of KRAS or NRAS or BRAF gene mutation and ECOG of 62% patients was 1. In addition, 59% patients were refractory to second standard line or above systemic therapy and mean interventional treatment cycles were 3.3. As the follow-up cutoff date was Dec 31, 2022, median duration of follow-up was 17.9 months (95% CI,16.185-19.615). Median hPFS was 8.7 months (95% CI, 6.744-10.658) while median PFS was 6.2 months (95% CI, 5.048-7.352). For the patients who were refractory to second line or above systemic therapy, hPFS and PFS was 6.2 months (95% CI, 4.899-7.501) and 5.2 months (95% CI, 3.682-6.718) respectively. Overall survival has not been reached yet. There were 7 patients achieved clinical complete response. Overall response rate was 41.6% and disease control rate was 82.2%. There was no treatment-related death. 28 patients (27.7%) experienced grade 3 or higher toxicities. The most common treatment related AE were aspartate transaminase/alanine transaminase elevation (41.6%) and bilirubin elevation (40.6%). The hematologic AE included anemia (27.7%), leukopenia (27.7%), neutropenia (14.9%) and thrombocytopenia (28.7%). Conclusions: The combination of Irinotecan-eluting HepaSphere chemoembolization and HAIC is effective and safe for unresectable CRCLM, even for patients who are refractory to second or above systemic therapy, indicating it is a promising regional treatment with improved outcome.
Real-world treatment trends and outcomes in elderly patients with metastatic colorectal cancer in the United States.
Authors: Trunk Andrew , Baron Margaret Kelsey , Smith Jarrod , Pappas Lisa M. , Haaland Ben , Florou Vaia , Nevala-Plagemann Christopher Duane , Garrido-Laguna Ignacio 
Published: June 2023

3591 Background: Prospective data to guide management of elderly patients with metastatic colorectal cancer (mCRC) is limited. Whether elderly patients derive the same degree of benefit from doublet chemotherapy as younger patients is not well understood. In this study we utilized real-world data from patients in the United States (US) to evaluate treatment trends and compare overall survival (OS) in younger versus older patients with mCRC who receive first-line (1L) chemotherapy. Methods: The nationwide Flatiron Health electronic health record-derived de-identified database was used to select patients ≥50 years old (yo) with mCRC treated with 1L fluoropyrimidine-based chemotherapy with or without the addition of targeted therapy. Overall survival from the initiation of 1L therapy, stratified by receipt of a doublet or single agent cytotoxic chemotherapy regimen was assessed independently within three age cohorts (50-69; 70-74, ≥75) using both a cox proportional hazard model and a propensity score weighted analysis to control for potential confounding variables. A subgroup analysis was performed in patients receiving bevacizumab as part of 1L therapy. Results: Of 14,440 patients who received 1L chemotherapy, 5,874 (40.7%) were ≥70 yo, including 3,656 (25.4%) who were 75 or older. Doublet chemotherapy was received by 7,505 (87.6%) patients age 50-64 yo, 1892 (85.3%) patients age 70-74 yo, and 2297 (62.2%) patients age 75 and above. In all three groups, multivariate analysis of single agent chemotherapy vs doublet chemotherapy showed a benefit to doublet chemotherapy with a hazard ratio of 1.14, (95% CI 1.04-1.24, p = 0.006), 1.22 (95% CI 1.05-1.42, p = 0.011) and 1.19 (95% CI 1.10-1.29, p < 0.001), respectively. Similar results were noted when comparing doublet to single agent chemotherapy in the age 70-74 and ≥75 groups using a propensity score weighted analysis. In the subgroup of patients age ≥70 who received 1L bevacizumab, 2,604 received doublet chemotherapy and 441 received single agent chemotherapy. Median OS was 19 mos (95% CI: 18-20) vs 13 (95% CI: 11-15) vs with a propensity score weighted HR of 1.35 (95% CI 1.12-1.63, p = 0.001). Conclusions: A smaller percentage of patients over age 75 receive 1L doublet chemotherapy for mCRC in the US compared to patients age 50-69 or 70-74. Regardless of age, patients who receive doublet fluoropyrimidine-based chemotherapy appear to have improved overall survival compared to single agent chemotherapy. This retrospective US data is in contrast with recently presented data from a prospective phase III trial in Japan (JCOG1018). Elderly patients in the US should not be excluded from receiving doublet chemotherapy for mCRC without further prospective data.
The significance of mucin on rectal MRI in patients with locally advanced rectal cancer being considered for watch-and-wait after neoadjuvant therapy.
Authors: Judge Sean , Malekzadeh Parisa , Corines Marina J , Gollub Marc J , Horvat Natally , Saltz Leonard B. , Cercek Andrea , Romesser Paul Bernard , Crane Christopher H , Wei Iris H , Widmar Maria , Pappou Emmanouil , Nash Garrett Michael , Smith Jesse Joshua , Paty Philip , Garcia-Aguilar Julio , Weiser Martin R. 
Published: June 2023

3614 Background: Neoadjuvant therapy (NAT) leads to a clinical complete response (cCR) in a significant proportion of patients with locally advanced rectal cancer (LARC) allowing for possible non-operative management. Along with physical exam and proctoscopy, magnetic resonance imaging (MRI) is used to evaluate for residual tumor following NAT. The presence of mucin on MRI leads to uncertainty about residual disease and appropriateness of watch-and-wait strategy (WW) in patients with no evidence of disease on proctoscopy (endoscopic cCR). We set out to determine the impact of radiographic mucin in patients with LARC after NAT. Methods: MRI reports between July 2016 to January 2020 at Memorial Sloan Kettering Cancer Center were queried for the presence of mucin in the tumor bed on post-treatment rectal MRI in patients with LARC following NAT. The clinicodemographic, pathologic, and outcomes data from these patients were compiled and analyzed. Results: Seventy-one patients were included in the final analysis who fit the pre-specified inclusion criteria (Table). Of the 71 patients with mucin present on post-treatment MRI, 19 patients (27%) entered a watch-and-wait (WW) strategy and 52 patients (73%) were planned for surgery (non-WW). Comparing the WW and non-WW cohorts, there was no difference in age, sex, clinical nodal status, or neoadjuvant regimen. Patients entering a WW protocol had a higher proportion of cT1-T2 tumors (32%) compared to non-WW (4%) (P < 0.01). All WW patients had endoscopic cCR, while only one non-WW patient achieved endoscopic cCR. Of 52 non-WW patients, 49 underwent resection and 3 did not have surgery due to disease progression. The pathologic complete response (pCR) rate in the non-WW patients who underwent surgery was 10%. Of 19 WW patients, 4 experienced regrowth (21%), while 15 (79%) have no local regrowth, with a median follow up of 4.2 years (range 2.4-6.3 yrs). Two patients (11%) experienced distant failure. Conclusions: The presence of mucin after NAT for LARC should not necessarily preclude a WW strategy in otherwise appropriate candidates who achieve an endoscopic cCR. [Table: see text]
Treatments and clinical outcomes in stage II colon cancer (CC) patients (pts) with 12-gene Oncotype DX Colon Recurrence Score assay-guided therapy: Real-world data.
Authors: Brenner Baruch , Shulman Yakatherina , Hubert Ayala , Man Sofia , Geva Ravit , Ben-Aharon Irit , Fennig Shlomit , Mishaeli Moshe , Yarom Nirit , Bar-Sela Gil , Brenner Ronen , Shay Ayelet , Soussan-Gutman Lior , Voet Hillary , Bareket-Samish Avital , Liebermann Nicky 
Published: June 2023

3620 Background: The role of adjuvant chemotherapy (CT) in stage II CC is debated. The validated 12-gene Oncotype DX Colon Recurrence Score test provides a Recurrence Score (RS) result (range, 0-100) which estimates recurrence risk (RR) in stage II/III pts. We studied treatment and clinical outcomes in CC pts in whom treatment decisions incorporated the RS result. Methods: This prospectively designed cohort study included all stage II, MMR-P, CC pts who underwent the 12-gene Oncotype DX testing through Clalit between 1/2011 and 12/2016 and had available data with minimum 3-yr follow-up. Kaplan-Meier (KM) estimates and log-rank tests were used to compare RR and CC specific mortality (CCSM) between RS categories. Multivariable analysis (MVA) identified variables associated with RR/CCSM. Results: The analysis included 938 pts. Median age, 68 (IQR, 60-76) yrs; 96% had T3 tumors, and 89% had ≥12 nodes examined. Median RS was 26 (IQR, 19-33). The 3 RS categories (0-29, 30-40, and 41-100) included 65%, 24%, and 11% of pts, respectively. The overall CT use rate was 24%, with a significant difference between the 3 categories (14%, 36%, and 60%, respectively, P< .0001). Pts with very low RS (0-15) comprised 14% of the cohort (CT use rate, 11%). Younger pts, and those with invasion/perforation/obstruction were more likely to receive CT. Clinical outcomes with a median follow up of 6.9 (IQR, 5.5-8.6) yrs are presented (Table). Among untreated pts, KM estimates for RR and CCSM differed significantly between the 3 RS categories ( P< .0001). Outcome of untreated RS 0-15 pts was excellent. In an MVA model, male sex, presence of invasion/perforation/obstruction and higher RS category (RS 41-100 vs 0-29 and vs 30-40, but not RS 30-40 vs 0-29) were associated with increased RR. For CCSM, the results were similar, but this time age ≥70 yrs replaced sex as a significant prognostic variable. Clinical outcomes within each RS group did not differ significantly between treated and untreated pts, but were numerically better with CT in the RS 41-100 group. Conclusions: This real-world analysis showed that the RS results provide independent prognostic information in stage II CC. Further studies are needed to investigate the potential role of the RS result as a predictor of CT benefit, but the data suggest that this benefit may be limited to pts with high RS results. [Table: see text]
Liposomal irinotecan + 5-fluorouracil/leucovorin + oxaliplatin (NALIRIFOX) versus nab-paclitaxel + gemcitabine in treatment-naive patients with metastatic pancreatic ductal adenocarcinoma (mPDAC): 12- and 18-month survival rates from the phase 3 NAPOLI 3 trial.
Authors: O'Reilly Eileen Mary , Melisi Davide , Macarulla Teresa , Pazo Cid Roberto A. , Chandana Sreenivasa R , De La Fouchardiere Christelle , Dean Andrew Peter , Kiss Igor , Lee Woo Jin , Goetze Thorsten Oliver , Van Cutsem Eric , Paulson Scott , Bekaii-Saab Tanios S. , Pant Shubham , Hubner Richard , Xiao Zhimin , Chen Huanyu , Benzaghou Fawzi , Wainberg Zev A. 
Published: June 2023

4006 Background: Liposomal irinotecan + 5-fluorouracil/leucovorin (5-FU/LV) is approved in the USA and Europe for mPDAC following progression with gemcitabine-based therapy. A phase 1/2 study (NCT02551991) demonstrated promising anti-tumor activity in patients with mPDAC who received first-line liposomal irinotecan 50 mg/m2 + 5-FU 2400 mg/m2 + LV 400 mg/m2 + oxaliplatin 60 mg/m2 (NALIRIFOX). Here, we present results from NAPOLI 3 (NCT04083235), a randomized, open-label, phase 3 study investigating the efficacy and safety of NALIRIFOX compared with nab-paclitaxel 125 mg/m2 + gemcitabine 1000 mg/m2 (Gem+NabP) as first-line therapy in patients with mPDAC. Methods: Eligible patients with histopathologically/cytologically confirmed untreated mPDAC were randomized (1:1; stratified by Eastern Cooperative Oncology Group [ECOG] performance status, geographic region and presence/absence of liver metastases) to receive NALIRIFOX on days 1 and 15 of a 28-day cycle or Gem+NabP on days 1, 8 and 15 of a 28-day cycle. The primary endpoint was overall survival (OS); secondary endpoints were progression-free survival (PFS), overall response rate (ORR) and safety. OS was evaluated when at least 543 events were observed using a stratified log-rank test with an overall one-sided significance level of 0.025. Results: Overall, 770 patients (NALIRIFOX, n = 383; Gem+NabP, n = 387) were included. Baseline characteristics were balanced between arms. At a median follow-up of 16.1 months, 544 events had occurred. Median OS was 11.1 months in the NALIRIFOX group versus 9.2 months in the Gem+NabP group; median PFS was 7.4 months versus 5.6 months. Median (95% CI) duration of response was 7.3 (5.8–7.6) and 5.0 (3.8–5.6) months in patients who received NALIRIFOX and Gem+NabP, respectively. Grade 3/4 treatment-emergent adverse events occurring in at least 10% of patients receiving NALIRIFOX versus Gem+NabP included diarrhea (20.3% vs 4.5%), nausea (11.9% vs 2.6%), hypokalemia (15.1% vs 4.0%), anemia (10.5% vs 17.4%) and neutropenia (14.1% vs 24.5%). Conclusions: First-line NALIRIFOX demonstrated clinically meaningful and statistically significant improvement in OS and PFS compared with Gem+NabP in patients with mPDAC. The NALIRIFOX safety profile was consistent with the profiles of the regimen components and generally manageable. Clinical trial information: NCT04083235 . [Table: see text]
A phase 2 study of HLX07 as monotherapy or combination therapy in patients with locally advanced, unresectable, or metastatic esophageal squamous cell carcinoma.
Authors: Huang Jing , Liu Yun , Wu Tao , Liu Zhen-yang , Zhou Jin , Yuan Yuan , Yang Mudan , Liu Bo , Tan Zhenbo , Zhuang Wu , Chen Jiayan , Liu Yanqing , Yu Haoyu , Wang Qingyu , Zhu Jun 
Published: June 2023

4029 Background: Esophageal cancer is one of the most common cancers worldwide with esophageal squamous cell carcinoma (ESCC) being the predominant histological subtype. Most patients are diagnosed at the advanced stage, and the prognosis remains poor. About 40–84% of ESCC cases showed overexpression of EGFR which was related to shorter overall survival and disease-free survival, indicating that treatment targeting EGFR could be a new strategy. This study aimed to evaluate the efficacy and safety of HLX07, a novel recombinant humanized anti-EGFR monoclonal antibody (mAb), as monotherapy or combination therapy in patients with locally advanced, unresectable/metastatic ESCC. Methods: In this open-label, multicenter phase 2 study, patients aged 18–75 years with histologically or cytologically confirmed locally advanced, unresectable/metastatic ESCC or esophageal adenosquamous carcinoma were enrolled. Patients with no prior systemic antitumor therapy were assigned to group A and given HLX07 1000 mg plus serplulimab 200 mg (anti-PD-1 mAb) and chemotherapy (5-FU 2400 mg/m2 + cisplatin 50 mg/m2), Q2W IV. Patients who had failed first-line immuno-chemotherapy combination or at least two lines of other systemic antitumor therapy were assigned to group B and given HLX07 monotherapy (1000 mg Q2W IV). The primary endpoints were objective response rate (ORR) and progression-free survival (PFS) assessed by an independent radiological review committee and investigators per RECIST v1.1. Secondary endpoints included other efficacy measures, safety, pharmacokinetics, immunogenicity, and biomarker explorations. Results: As of February 4, 2023, 49 patients were enrolled in group A (n=30) and group B (n=19), with a median age of 64.5 and 59.0 years, respectively. 26 (86.7%) patients in group A and all patients in group B were male. The median follow-up duration was 2.9 months, and the preliminary efficacy was presented. Among the 42 efficacy evaluable patients (29 in group A and 13 in group B), investigator-assessed ORRs were 55.2% (95% CI 35.7–73.6%) and 23.1% (95% CI 5.0–53.8%) in the respective groups. Investigator-assessed median PFSs were not reached in group A and 1.5 months (95% CI 1.2–not evaluable) in group B. 15 (50.0%) patients in group A and 5 (26.3%) in group B had grade ≥3 treatment-emergent adverse events (AEs). AEs of special interest were observed in 16 (53.3%) and 11 (57.9%) patients, respectively, most commonly rash (43.3% vs 47.4%) and hypomagnesemia (33.3% vs 36.8%). No drug-related death was reported. Conclusions: The encouraging antitumor activity and manageable safety profile support further development of HLX07 as a new treatment option for patients with advanced ESCC, both in first-line and late-line settings. Clinical trial information: NCT05221658 .
Cell free DNA (cfDNA) assessment of esophagogastric (EG) cancer using MSK-ACCESS.
Authors: Cytryn Samuel Louis , Solit David B. , Walch Henry S. , Chatila Walid Khaled , Maron Steven Brad , Vakiani Efsevia , Brannon Angela Rose , Ladanyi Marc , Schultz Nikolaus , Berger Michael F. , Janjigian Yelena Y. 
Published: June 2023

4036 Background: The incidence of EG cancer is rising, the treatment paradigm is increasingly complex, and the role of predictive biomarkers is critical in selecting optimal therapies. Therefore, longitudinal, non-invasive methods to characterize dynamic tumor molecular profiles, such as cfDNA, are needed. Methods: Patients with EG cancer receiving care at Memorial Sloan Kettering (MSK) had cfDNA analysis with an ultrasensitive capture based liquid biopsy for detection of somatic alterations in 129 cancer associated genes (MSK ACCESS). Tumor samples were analyzed with MSK-IMPACT, a capture based next generation sequencing (NGS) platform. Results: 100 patients with EG adenocarcinoma underwent cfDNA analysis to evaluate for molecular residual disease with MSK ACCESS. 85 (85%) had tissue NGS with MSK IMPACT. Median TMB was 5.3 mut/Mb (IQR 2.6-7.4) and median number of alterations per sample was 11 (IQR 7-17). 71% had TP53 mutations and 22% had an ERBB2 amplification (amp). 79 (79%) patients had cfDNA obtained prior to treatment (50 [63%] metastatic disease; 29 [37%] localized disease) and 21 (21%) at the time of progression. Alterations were detectable on cfDNA more frequently in patients with later stage disease (p=0.031) and fewer alterations per sample were detected compared to tissue NGS (mean difference 14, 95% CI 10-18, p<0.001). The most common were TP53 (62%), CDKN2A (12%), PIK3CA (10%), ARID1A (10%), and ATM (10%). TP53 was detected with increasing frequency in patients with later stage disease (p=0.004). However, amplifications, which included ERBB2, MYC, EGFR, and FGFR2, were detected exclusively in those with stage IV disease (p=0.005) and cfDNA was less sensitive in detecting amplifications compared to tissue NGS (p<0.001). This is notable as HER2 positivity is determined in part by ERBB2amp. 25 of 30 HER2+ patients had both tissue NGS and cfDNA. 19 (76%) had ERBB2amp on tissue NGS and only 8 (32%) had ERBB2amp on cfDNA (p=0.004). Additionally, copy number was lower on cfDNA compared to tissue NGS (mean difference 13, 95% CI 1.3-24.9, p=0.02) and IHC 3+ tumors were more likely to have ERBB2amp detected than IHC 2+ tumors (p=0.049). However, alterations along the MAPK, PI3K, WNT, and TGF-β pathways, which are associated with trastuzumab resistance and poor survival, were detected with similar frequency on both platforms (40 v 32%, p=0.77). Conclusions: Our findings in this large prospective analysis highlight the utility of cfDNA with MSK ACCESS as a complimentary tool for molecular characterization in patients with EG cancer. cfDNA in EG cancer. [Table: see text]
Advancing individualized care in advanced gastroesophageal cancers (GEC): A quality improvement initiative.
Authors: Strickland Matthew , Delcuze Bethany , Dewald Ilona , McKinnon Kelly E. , Carter Jeffrey D. , Heggen Cherilyn 
Published: June 2023

4051 Background: Biomarkers have become increasingly important in the treatment of metastatic gastroesophageal cancers (mGEC) with new targeted and immune-based therapies relying on biomarkers to identify patients who may benefit from these therapies. Here, we aimed to identify real-world challenges mGEC care teams face in implementing biomarker testing and evidence-based treatment choices. Methods: In July–September 2022, 74 health care professionals (HCPs) who treat mGEC at 3 US community oncology clinics completed surveys assessing practice patterns, challenges, and confidence related to treating mGEC. HCPs (N = 24) participated in interdisciplinary audit and feedback (AF) sessions to examine clinical evidence and develop clinic-specific action plans to address identified gaps. Results: Participating practices reported that ~22% of their practice is dedicated to GEC care. Participants represented the interprofessional GEC care team: medical oncologists (27%), radiation oncologists (1%), surgeons (1%), advanced practice professionals (32%), nurse/nurse navigators (32%), and other HCPs (5%). Providers reported testing for HER2, EGFR, FGFR, NTRK, microsatellite instability, tumor mutational burden, and PD-L1 in ~55-65% of advanced GEC patients. Most providers reported HER2 testing at time of diagnosis (91%) with 18% reporting testing at time of clinical or radiologic progression and 24% when new metastases are detected. Top reported barriers to use of predictive biomarker testing were long turnaround times for tests (32%) and keeping up to-date with current testing recommendations (23%). Top reported challenges in selecting therapies for GEC were keeping up with clinical evidence (35%) and delayed, pending, or unavailable biomarkers at the time of treatment selection (20%). Clinic action plans focused on specific gaps including (1) improved HCP education on guideline-concordant biomarker use (2) improving testing turnaround times, and (3) improving referrals to clinical trials based on biomarker results. The educational intervention increased correct identification of guideline concordant treatment for stage IV esophageal cancer (48% pre- and 72% post-AF) and confidence in use of biomarkers for treatment decision-making for patients with GEC (high/very high in 46% pre- and 72% post-AF). Conclusions: While molecular testing is becoming increasingly critical for mGEC care, HCPs report challenges with testing workflows and difficulty keeping up with developments in clinical data and guidelines. Clinic-specific interventions to improve biomarker workflows and ongoing educational initiatives to keep HCPs informed of the latest evidence-based best practices in biomarkers and associated therapies can address these gaps to improve outcomes for patients with GEC.