bluuebunny/crossref_metadata_2025_split huggingface dataset:
The distribution of human epidermal growth factor receptor 2 (HER2) expression and the efficacy and safety of treatments in HER2-expressing advanced or metastatic gastroesophageal cancer: A systematic literature review (SLR).
Authors: Zhen David Bing , Schwartz Naomi RM , Beckerman Rachel , Stricker-Shaver Janicec , Zhu Mingshu , Gadikota Hemanth , Scherrer Emilie 
Published: January 2024

405 Background: HER2 overexpression plays an important role in determining treatment options for patients with gastroesophageal cancer (GEC). HER2 overexpression has historically been defined dichotomously as HER2-positive (HER2+) or HER2-negative. An emerging potentially clinically relevant category is HER2-low, which could be targeted with HER2-directed antibody drug conjugates. However, data on the epidemiology and outcomes associated with HER2-low GEC are limited. Methods: An SLR of PubMed, Embase, and Cochrane Central Register of Controlled Trials databases was conducted to identify clinical trials, observational studies, and meta-analyses reporting clinical outcomes or distribution of HER2 expression by IHC and ISH in advanced or metastatic (a/m) GEC. Key inclusion criteria were: English language, published between 2013-2023, and sample size ≥100 HER2-expressing patients. HER2+ was defined as IHC score of 3+ or IHC 2+ and ISH+. HER2-low was defined as IHC 1+ or IHC 2+ and ISH-. Weighted averages were calculated for the proportion of patients who were HER2+ and HER2-low to estimate of the proportion of patients in each HER2 expression category. Results were categorized by patient population (all GEC or gastric cancer [GC] only). Results: Of 2,701 non-duplicated records screened, 174 studies met inclusion criteria. Distribution of HER2 expression was reported in 111 studies, 5 of which reported on the frequency of HER2 expression of IHC 1+ and/or IHC 2+ and ISH+. HER2 expression status varied by patient population, with a weighted average of 26.9% for HER2-low and 13.1-16.5% for HER2+ across groups (Table). Different cutoffs for HER2 amplification via ISH also affected the proportion of patients in each HER2 category across studies. Efficacy and safety outcomes were stratified by HER2 status or IHC results in 74 studies. However, only 3 observational studies reported outcomes separately for the HER2-low population, and results were inconclusive. Conclusions: The distribution of HER2 expression in a/m GEC in the identified studies is highly heterogenous, likely due to variability in IHC scoring and patient populations. Few studies with sufficient samples size (≥100 patients with HER2-expression a/mGEC) reported outcomes for HER2-low a/m GEC, and those that were identified were of low quality. The HER2-low a/m GEC population constitutes an unmet need for effective therapy. There is a need for consistent use of a standardized definition of HER2-low in a/mGEC and additional studies to better evaluate treatment options and outcomes for this patient population. [Table: see text]
Cell free DNA (cfDNA) assessment of esophagogastric (EG) cancer using MSK-ACCESS.
Authors: Cytryn Samuel Louis , Phu William , Shah Ronak H. , Walch Henry S. , Chatila Walid Khaled , Vakiani Efsevia , Brannon Angela Rose , Ladanyi Marc , Srivastava Amitabh , Tang Laura H. , Strong Vivian E. , Molena Daniela , Solit David B. , Berger Michael F. , Janjigian Yelena Y. 
Published: January 2024

406 Background: Treatment for EG cancer is increasingly complex and the role of predictive and prognostic biomarkers is critical in selecting the optimal therapy. Longitudinal, non-invasive methods that characterize dynamic molecular profiles and detect molecular residual disease 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). Results: 98 patients with EG adenocarcinoma underwent cfDNA analysis; 18% had esophageal tumors, 44% had GEJ, and 38% had gastric. 78 (80%) patients had cfDNA obtained prior to treatment (48 [50%] metastatic; 29 [30%] locally advanced) and 21 (21%) at time of progression. 85% had matched tumor NGS performed with MSK IMPACT: median TMB was 5.3 mut/Mb (IQR 3.3-7.4) and median alterations per tumor sample was 11 (IQR 7-17). cfDNA identified a similar molecular profile compared to tumor NGS (TP53 [62 v 72%], ARID1A [12 v 20%], CDKN2A [10 v 16%], APC [10 v 13%], ATM [10 v 12%], PIK3CA [7 v 12%]), although cfDNA was detected more frequently in patients with metastatic disease compared to localized disease (p=0.02). cfDNA did not detect copy number alterations as frequently as patient-matched tumor NGS (41 v 16%, p<0.01), including ERBB2amp (22 v 10%, p=0.05), though patients with HER2 IHC 3+ tumors were more likely to have detectable ERBB2amp on cfDNA compared to HER2 IHC 2+ tumors (50 v 9% p=0.03). Additionally, those with detectable ERBB2amp on cfDNA had a higher copy number on tumor NGS compared to those with undetectable cfDNA (median 39 [IQR 23-46] v 10 [IQR 6-15] p<0.01). Baseline detection of ctDNA may indicate a poor prognosis; among patients with locally advanced disease (median follow up 20.1 months), 0 of 10 with undetectable ctDNA died compared to 5 (26%) of 19 with detectable ctDNA (p=0.08). Among patients with untreated, metastatic disease (median follow up 24.3 months), patients with undetectable ctDNA had a non-significant, improvement in PFS (HR 0.28 95% CI 0.08-1.17; p=0.08) and OS (HR 0.45 95% CI 0.10-1.96; p=0.20) compared to patients with detectable ctDNA, independent of disease burden. Conclusions: Our findings highlight the utility of cfDNA with MSK ACCESS as a complimentary tool for molecular characterization and potential prognostication in patients with EG cancer. [Table: see text]
Survival after esophagectomy for metastatic esophageal cancer: Should surgery’s role be reconsidered?
Authors: Saeed Samir H , Sinnamon Andrew J , Fontaine Jacques P , Mehta Rutika , Baldonado Jobelle Joyce Anne , Pena Luis R , Palm Russell F , Hoffe Sarah E. , Frakes Jessica M. , Pimiento Jose Mario 
Published: January 2024

410 Background: Standard treatment for stage IV esophageal cancer (EC) is systemic therapy, with surgery considered contraindicated. The objective of this study is to assess the impact of surgical resection on outcomes for patients with metastatic EC. Methods: We reviewed our institution’s IRB-approved database of 1334 esophagectomies from 1994 to 2023 and identified 18 patients with distant disease (stage IV) by AJCC8 found prior to or during surgery. Chi-Square, ANOVA, and Kaplan-Meier survival analyses were used to compare demographics, clinical characteristics, and survival from time of surgery in those with metastatic versus non-metastatic EC. Results: Most metastatic patients were male (89%), Caucasian (83%), and had adenocarcinoma (89%). Compared to the non-metastatic cohort, stage IV EC cases were younger (57 vs 63; p=0.03), non-Caucasian (17% vs 6%; p=<0.001), and more likely to get chemotherapy (41% vs 8%; p=0.04) or immunotherapy (23.5% vs 0%; p=0.06), with no difference in gender (89% vs 83%) and receipt of chemoradiotherapy (94% vs 92%). While the difference in intra-operative complication rates was significant (13% vs 2%; p=0.001), both groups had similar rates of post-operative complications ( p=0.95). Non-regional nodal metastasis had the most favorable outcome (mOS NR; median follow-up=14m); while peritoneal/omental disease had the shortest survival (5.2m). Patients receiving surgery more than a year after stage IV diagnosis ( n=6) had better survival than those who either underwent resection within a year after diagnosis ( n=2) or had metastasis identified at time of surgery ( n=8) ( p=0.02). PDL-1 positive and HER2-neu positive tumors also had better outcomes, with neither group reaching median survival. Conclusions: Esophagectomy for highly selected patients with distant disease demonstrates similar post-operative complication rates to locally advanced EC. For stage IV patients, a short interval from diagnosis to surgery is associated with worse survival; however, prolonged diagnosis-to-surgery interval >12m and PDL-1 and HER2-neu positivity demonstrate better outcomes. Surgery’s role in treatment of stage IV EC preferably more than a year after diagnosis of metastasis should be further studied.
Correlation between postoperative systemic inflammatory response and prognosis in patients with advanced gastric cancer.
Authors: Kuroda Kenji , Toyokawa Takahiro , Miki Yuichiro , Yoshii Mami , Kasashima Hiroaki , Fukuoka Tatsunari , Tamura Tatsuro , Shibutani Masatsune , Lee Shigeru , Yashiro Masakazu , Maeda Kiyoshi 
Published: January 2024

411 Background: Several studies have shown that postoperative infectious complications correlate with poor prognosis in various malignancies, but the prognostic significance of the postoperative inflammatory response in patients with gastric cancer remains unclear. The aim of study was to examine whether the systemic inflammatory response present in the early phase of the postoperative state correlates with long-term outcomes and to identify markers in patients with advanced gastric cancer. We evaluated C-reactive protein (CRP) and white blood cell (WBC) count as simple and versatile markers of postoperative systemic inflammation in clinical practice that may be suitable for detecting the magnitude of inflammatory reaction. Methods: This study retrospectively reviewed 444 patients who underwent radical gastrectomy for stage II/III gastric cancer. We evaluated maximum serum C-reactive protein (CRPmax) and white blood cell count (WBCmax), defined as the maximum serum CRP level and maximum WBC count during the interval from surgery until discharge, as systemic inflammation markers. Results: In univariate analyses, CRPmax, WBCmax and infectious complications were significantly associated with both overall survival (OS) (p<0.001, p<0.001 and p=0.011, respectively) and relapse-free survival (RFS) (p<0.001, p=0.001 and p<0.001, respectively). Multivariate analysis revealed that high CRPmax (>9.2 mg/dL) was an independent prognostic factor for OS (hazard ratio (HR) 1.69, 95% confidence interval (CI) 1.18–2.42, p=0.004) and RFS (HR 1.42, 95%CI 1.02–1.98, p=0.038), while WBCmax and infectious complications were not. Regarding the pattern of recurrence, hematogenous recurrence was significantly more frequent in the high-CRPmax group (16.7%) than in the low-CRPmax group (3.8%, p<0.001). Conclusions: CRPmax, which reflects the magnitude of systemic inflammation induced by surgical stress and postoperative complications in the early phase after surgery, may be a promising prognostic indicator in patients with stage II/III gastric cancer who undergo curative resection.
Genomic profile and clinical feature of esophageal squamous cell carcinoma, focusing on MSI, TMB, and HRD status: Analysis with the national database of Japan.
Authors: Morita Ryuichi , Ishikawa Takeshi , Doi Toshifumi , Itani Junichiro , Sone Daiki , Iwasaku Masahiro , Konishi Hirotaka , Shiozaki Atsushi , Fujiwara Hitoshi , Konishi Hideyuki , Takayama Koichi , Itoh Yoshito 
Published: January 2024

412 Background: In Japan, cancer genome profiling (CGP) testing has been widely used from 2019, and genomic and clinical information integrated into national database (C-CAT database) is now available for secondary use for innovative research. In esophageal squamous cell carcinoma (ESCC), more than 500 patients (as of December 2022) have already undergone CGP testing. MSI-H and TMB-H ESCC are rare, and information is lacking. Using C-CAT data base, we analyzed the clinical and genomic characteristics of ESCC, especially focusing on MSI, TMB, and HRD status. Methods: We retrospectively reviewed data on 535 cases with ESCC enrolled in C-CAT between June 2019 and December 2022. The clinical features, genomic variants classified as oncogenic/pathogenic, MSI/TMB status and response to treatment (response rate; RR and time to treatment failure; TTF) were evaluated. Results: Oncogenic/pathogenic variants were detected in 527 cases (98%), and the Top 5 gene mutations were TP53 (94.6%), CDKN2A (56.6%), CDKN2B (43.7%), CCND1 (42.6%), and FGF19 (38.9%), in order of prevalence. No patient had MSI-H, and number of patients with TMB-H (≥10 Muts/Mb) and HRD were 82 (15%) and 15 (13%), respectively. Regarding the efficacy of first-line chemotherapy (IO-containing regimen in 5 cases, 0.9 %), the TTF was significantly shorter in TMB-H cases than in TMB-L cases (11.8 vs 17.5 weeks, p=0.006). No difference in response to anti-PD-1 antibody was observed depending on TMB status (RR, TMB-L 19 % vs. TMB-H 12 %). Patients with BRCA1/2 mutations tended to respond better to first-line chemotherapy including platinum drugs, although there was no difference in response to treatment with or without other HRR mutations. The percentages of cases delivered new treatments based on CGP testing was 6.8%. The percentage of cases with HRD or TMB-H suggested new treatment based on GCP testing was significantly higher than those without them. Conclusions: Patients with BRCA1/2 mutations are more sensitive to platinum combination chemotherapy and may be good candidates for PARP inhibitors in ESCC. Since TMB-H patients are resistant to standard chemotherapies, we should promote the development of immunotherapy and molecular-based targeted therapies for this population.
Assessing risk stratification in long-term outcomes of rectal neuroendocrine tumors following endoscopic resection: A multicenter retrospective study.
Authors: Seo Yeonjoo , Lee Han Hee , Kim Jin Il 
Published: January 2024

42 Background: The detection of rectal neuroendocrine tumors (NETs) has increased with advances in diagnostic endoscopy. Endoscopic resection (ER) is a highly effective treatment option for rectal NETs confined to . We aimed to analyze the long-term outcomes of patients with rectal NETs after ER. Methods: In this multicenter retrospective study, we included patients who underwent ER of rectal NETs from 2009 to 2018 and were followed for ≥12 months at five university hospitals. We classified the patients into three risk groups according to the clinicopathological status of the rectal NETs: low, indeterminate, and high. The high-risk group was defined if the tumors have any of the followings: size ≥ 10 mm, lymphovascular invasion, muscularis propria or deeper invasion, positive resection margins, or mitotic count ≥2/10. Results: In total, 346 patients were included, with 144 (41.6%), 121 (35.0%), and 81 (23.4%) patients in the low-, indeterminate-, and high-risk grouprespectively. In the high-risk group, seven patients (7/81, 8.6%) received salvage treatment 28 (27–67) days after the initial ER. There was no extracolonic recurrence in any of the 7 patients. During the follow-up period of all included patients, 1.1% (4/346) had extracolonic recurrences at 56.5 (54–73) months after initial ER. Three of these patients (75%) were at a high risk without salvage treatment. The risk of extracolonic recurrence was significantly higher in the high-risk group than in the other groups (p=0.039). Conclusions: The prognosis of patients who underwent ER for rectal NETs was favorable. Physicians should be concerned about the possibility of metastasis during long-term follow-up of high-risk patients and consider salvage treatment. [Table: see text]
Hepatic arterial infusion pump chemotherapy in patients with advanced intrahepatic cholangiocarcinoma confined to the liver: A multicenter phase II trial.
Authors: Franssen Stijn , Rousian Merve , Nooijen Lynn E. , ten Haaft Britte H.E.A. , Doukas Michael , Haj Mohammad Nadia , Klümpen Heinz-Josef , Moelker Adriaan , Mostert Bianca , Hagendoorn Jeroen , Swijnenburg Rutger-Jan , Homs Marjolein Y.V. , Groot Koerkamp Bas 
Published: January 2024

433 Background: In the ABC-trials, the 3-year overall survival (OS) was only 2.8% for patients with advanced intrahepatic cholangiocarcinoma (iCCA) confined to the liver who received systemic gemcitabine with cisplatin. Hepatic arterial infusion pump (HAIP) combined with systemic chemotherapy had a pooled 3-year OS of 39.5% in a recent meta-analysis. HAIP chemotherapy involves continuous administration of floxuridine (FUDR) directly into the hepatic artery using a subcutaneous pump. The aim of this study was to prospectively assess the effectiveness of HAIP with systemic chemotherapy in patients with advanced iCCA confined to the liver in the Netherlands. Methods: We performed a single arm phase II trial in 3 centers in the Netherlands. Six cycles of HAIP chemotherapy with floxuridine were scheduled with 8 cycles of concurrent systemic chemotherapy with gemcitabine and cisplatin, if not administered previously. The primary endpoint was OS, secondary endpoints were progression-free survival (PFS) and objective response. Results: From January 2020 until September 2022, 50 patients with advanced iCCA were included. Combined HAIP and systemic chemotherapy was administered to 38 patients (76.0%). Eleven patients (22.0%) received HAIP chemotherapy alone, because they had received systemic treatment before enrollment. One patient (2.0%) didn’t start treatment, because he died 19 days after pump implantation due to COVID-19. The median follow-up was 26.4 months (95% CI: 21.7 – 39.0). The median OS was 22.1 months (95% CI: 19.7 – not reached). The 1-year OS rate was 80.0% (95% CI: 69.6% – 91.9%); the 3-year OS rate was 28.6% (95% CI: 16.0% – 51.2%). The median PFS was 10.0 months (95% CI: 8.7 – 12.2). An objective response on imaging (RECIST) was achieved in 27 patients (54.0%) and disease control at 6 months in 43 patients (86.0%). Four patients (8.0%) underwent a resection after HAIP chemotherapy of whom 2 patients had a complete pathologic response. Conclusions: Combined HAIP with systemic chemotherapy for patients with advanced iCCA was associated with a favorable 3-year OS of 28.6% compared with 2.8% after systemic chemotherapy alone in the ABC trials. Clinical trial information: NL8234 .
Epidemiology, treatment patterns, and humanistic and economic burden of biliary tract carcinoma: A systematic and targeted literature review.
Authors: Kamble Shital , Desai Kaushal , Joo Seongjung , Pandey Prabhakar , Swami Shilpi , Habila Magdiel , Malhotra Usha , Hall Adam , Khatri Urvi , Nathani Jyothsna 
Published: January 2024

443 Background: Patients with biliary tract cancers (BTC) are typically diagnosed at late stage, with limited treatment options. As such, BTC is associated with poor prognosis, high economic burden and reduced health-related quality of life (HRQoL). As the treatment paradigm is evolving, with multiple immunotherapies showing promise, this study aimed to assess the current disease and treatment landscape. Methods: Systematic literature reviews (Embase, MEDLINE, Cochrane, NHS-EED; database inception to Feb 10, 2023) were conducted for HRQoL and economic burden. Targeted literature reviews (Embase, MEDLINE) were conducted for epidemiology (Jan 01 2017–Feb 06 2023) and treatment guidelines/patterns (Jan 01 2012–Feb 06 2023). Conference abstracts were also searched (2019–2022). Eligibility criteria included global studies (English language) in adults with metastatic and/or unresectable BTC. Results: Overall, 264 studies were included (epidemiology=170, treatment guidelines=14, treatment patterns=50, HRQoL=12, economic burden=18). In the US, Europe and Asia, age-standardized incidence rates were 5.04, 8.39–8.78 and 9.1–10.1 (per 100,000 person-years) and prevalence rates were 0.01%, 0.02–0.34% and 0.02–2.61%, respectively. Treatment pattern studies were mainly from Asia, Europe (n=19 each) and North America (n=10). Gemcitabine [gem]-based chemotherapy was most common in 1L BTC (24–100%) and fluorouracil-based regimens were common in 2L+ BTC (12.3–74.3%). Median overall survival (mOS) for gem-based and fluorouracil-based 1L regimens were 7.7–14.8 months and 7–16.7 months, respectively. Disease progression/toxicity frequently led to treatment discontinuation/dose modifications. In the US, use of non-guideline-based regimens increased by line of therapy (LOT). Among the clinical studies (n=5) reporting HRQoL in 1L, n=4 assessed gem-based combinations. BTC impaired HRQoL domains for anxiety, tiredness (EORTC QLQ-BIL21), work productivity, activity impairment (WPAI scale) and depression (PHQ-9). BTC was associated with substantial economic burden. Mean total all-cause healthcare costs per patient per month (PPPM) increased by LOT (US; 1L: $19,589–25,517, 2L: $22,617–29,721, 3L: $23,256–33,534). US healthcare resource utilization in 1L was driven by outpatient visits (98%), emergency department visits (33–80%) and hospitalization (70–80%). Mean hospital stay ranged from 0.6–7 days PPPM. Conclusions: Epidemiology data varied between Western and Asian populations, but gem-based chemotherapy was identified as the standard of care across regions. There is high unmet need in advanced BTC, as existing options are characterized by poor survival outcomes and considerable economic burden. These findings indicate a need for novel approaches for the management of BTC.
Patient-reported outcomes (PROs) <65 or ≥ 65 years old (yo) from CARES-310 camrelizumab + rivoceranib vs sorafenib as first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).
Authors: Chan Stephen Lam , Kaseb Ahmed Omar , Shi Wei , Alexander Laura , Meng Xianzhang , Park CheolHee , Ryan Kristin , Vogel Arndt 
Published: January 2024

456 Background: CARES-310 (NCT03764293) evaluated the combination of the anti-PD-1 inhibitor, camrelizumab (cam), and the VEGFR-2 tyrosine kinase inhibitor, rivoceranib (rivo), compared to sorafenib (sor) for the treatment of uHCC. Cam + rivo significantly improved OS and PFS compared to sor (OS, 22.1 months [mo] [95% CI 19.1-27.2] vs 15.2 mo [13.0-18.5] HR 0.62 [95% CI 0.49-0.80]; one-sided p<0.0001); PFS, 5.6 mo [95% CI 5.5-6.3] vs 3.7 mo [2.8-3.7]; HR 0.52 [95% CI 0.41-0.65]; one-sided p<0.0001). The most common (≥20%) grade ≥3 treatment-related adverse events for cam + rivo were hypertension (37.5%) and increased AST (16.5%) vs palmar-plantar erythrodysesthesia syndrome (15.2%) for sor. This analysis evaluated PROs stratified by age: <65 yo (baseline, overall cam + rivo n=191, sor n=210) or ≥65 yo (baseline, overall cam + rivo n=81, sor n=61). Methods: Patients completed EORTC QLQ-C30 and EORTC QLQ-HCC18 at baseline, each visit, and post-last-dose follow-up periods. Endpoints included time to deterioration (TTD) with a ≥10-point decrease from baseline of patient reported QoL, physical functioning, role functioning, and patient-reported symptoms. Results: Mean completion rates across questionnaires were 98.56% and 96.78% for cam + rivo and 98.91% and 98.75% for sor in the <65 and ≥65 yo groups, respectively, from baseline through ≥121 weeks of treatment. In the <65 yo group, cam + rivo vs sor had improved TTD in fatigue measured by EROTC-QLQ-C30. In the ≥65 yo group, cam + rivo had significantly longer median TTD of pain measured by EROTC-QLQ-HCC18 and QLQ-C30, respectively. The median TTD of appetite loss in the ≥65 yo group favored cam + rivo. Median TTD for jaundice was significant for sor in both <65 yo and ≥65 yo group. Median GHS/HRQoL in the ≥65 yo group favored cam + rivo. Conclusions: Cam + rivo was associated with improvement in varied QoL aspects in both patient groups. These PRO results support the clinical benefit and use of cam + rivo in patients with uHCC who have not received prior systemic therapy. Clinical trial information: NCT03764293 . [Table: see text]