bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular profiling of gastric neuroendocrine carcinomas.
Authors: Ikegame Ko , Hatakeyama Keiichi , Terashima Masanori , Sugino Takashi , Aizawa Daisuke , Furukawa Kenichiro , Fujiya Keiichi , Tanizawa Yutaka , Bando Etsuro , Yamaguchi Ken 
Published: January 2023

451 Background: Reports of comprehensive genetic analysis of gastric neuroendocrine carcinoma (G-NEC) are limited, and few have described the tumorigenesis of G-NEC. G-NEC usually has NEC and adenocarcinoma components and is considered to have a common origin in gastric adenocarcinoma because these two tumors share common pathogenic mutations and loss of heterozygosity. However, G-NEC without adenocarcinoma also exists, and it may have a different mechanism of tumorigenesis than that of G-NEC with adenocarcinoma. This study aimed to elucidate the tumorigenesis of G-NEC by focusing on the percentage of NEC component, using comprehensive genetic analysis. Methods: Of the 698 patients who had undergone gastrectomy for gastric cancer between January 2014 and March 2019, this study included 13 patients with G-NEC. Comprehensive genetic analysis using whole-exome sequencing, deep sequencing using a target gene panel, and microarray analysis were performed. NEC was classified according to the 2010 WHO classification. G-NEC without an adenocarcinoma component was defined as pure NEC. Results: There were six patients with mixed adeno-neuroendocrine carcinoma (MANEC), four patients with NEC, and three patients with pure NEC. TP53 was detected as the most frequent gene mutation, independent of classification (85%). RB1, ANKRD17, KMT2C, LTBP1, MAATS1, and RYR2 mutations were identified in two of three pure NEC patients but were not detected in other G-NEC patients. Gene expression analysis showed that six key transcripts of importance in NEC tumorigenesis were upregulated in two patients with pure NEC, while they were downregulated in all six MANEC patients. Conclusions: NEC and MANEC with adenocarcinoma components tend to share common pathogenic mutations, but Pure NEC has different genomic and transcriptomic characteristics than other NECs. This suggests that pure NEC has a different mechanism of tumorigenesis than other G-NECs with adenocarcinoma. This is the first study to present a comprehensive genetic analysis of G-NEC, classified by the percentage of NEC components.
Clinicopathologic features of early-onset (EO) esophageal and gastric cancers.
Authors: Lochrin Sarah Elizabeth , Deac Oana , O'Sullivan Jacintha , Cunningham Moya , Ravi Narayanasamy , Donohoe Claire L , O'Kane Grainne M. , Reynolds John V. , Lowery Maeve Aine 
Published: January 2023

472 Background: The rates of gastric (GC) and esophageal adenocarcinoma (EA) among individuals younger than age 50 years have increased by 30% and 50%, respectively, over the past three decades in the US. There is limited information on incidence and demographics for EO esophageal and gastric cancer in Europe. Methods: We conducted a retrospective review of the prospectively maintained upper gastrointestinal (UGI) cancer database in St James’s Hospital (SJH), the National Centre for Oesophageal and Gastric Cancer in Ireland. We reviewed all cases diagnosed with esophageal cancer (EC) and gastric cancer (GC) less than or equal to 50 years of age from 2000 to 2021. Results: From 2000 to 2021, 374 EO EA & GC cases were identified, 8% of the 4663 total EC & GC cases. The results are presented in the table. Conclusions: The major presenting symptoms for EO-UGI cancer were dysphagia, weight loss and dyspepsia, further investigation is warranted in young patients presenting with these symptoms, even in the absence of elevated BMI or other known risk factors for malignancy. A high proportion have advanced disease at diagnosis despite good PS and clinical outcomes are poor. There is a critical need to understand the pathogenesis of EO-UGI cancers to determine optimal strategies for prevention and management.[Table: see text]
Clinical outcomes of appendix goblet cell adenocarcinoma and role of systemic chemotherapy.
Authors: Strach Madeleine Cornelia , Chakrabarty Bipasha , Nagaraju Raghavendar , Aziz Omer , O'Dwyer Sarah , Barriuso Jorge 
Published: January 2023

50 Background: Appendix goblet cell adenocarcinomas (GCA) are rare aggressive tumours with patients often presenting with peritoneal metastases. Cytoreductive surgery and heated intraperitoneal chemotherapy (CRS/HIPEC) can be curative treatment and the role of systemic chemotherapy less defined. There is a need to better understand factors that predict outcome alongside assessment of the latest WHO 2019 classification. Methods: Demographics, clinicopathological variables, treatment characteristics and survival of patients with GCA from a UK peritoneal tumour centre were identified through a prospective database (2005-2021). Patients were selected for CRS/HIPEC based on disease burden. Pathology records were reviewed and those previously classified by Tang grading were reclassified to WHO 2019. The primary endpoint was overall survival (OS). Analysis was by the Kaplan-Meier method. Results: We identified 177 patients with GCA who had a median follow-up of 67 months (m, 4-207). Mean age at diagnosis was 57 years (22-79) and 88 were female (50%). There were 99 patients (56%) who had localised disease (M0) and 74 (42%) who had metastatic disease (M1). There were 126 (71%) patients who had CRS and 115 (91%) had HIPEC (65% MMC, 25% Oxaliplatin); median peritoneal cancer index score was 1 (0-28) and 12 (10%) patients had M1 disease. There were 72 (41%) patients who had systemic chemotherapy (72% oxaliplatin with fluoropyrimidine) and of those who had CRS, four had neoadjuvant, 18 adjuvant and the rest palliative intent chemotherapy. Incomplete CRS resulted in shorter OS compared to complete CRS (median 23 v 103m, p<0.001). Patients with involved nodes had shorter OS (32m v not reached, NR, p<0.001) compared to those with uninvolved nodes. WHO 2019 grade 2 predicts for longer OS than Tang B (median 118 v 54m, p=0.031). The table shows univariate survival according to grade and chemotherapy. Conclusions: This study represents the largest series of pure appendix GCA with long term follow-up data. Patients with positive lymph nodes and incomplete CRS had poor survival outcomes. The WHO 2019 classification had no direct prognostic correlation with the previous Tang classification. WHO 2019 grade 2 had longer OS compared to Tang B suggesting further stratification of the grade 2 group could be considered. Patients who had systemic chemotherapy had shorter OS and DFS as expected based on the selection of patients with higher grade, lymph node involvement and higher disease burden as part of clinical practice. [Table: see text]
Impact of etiology of hepatocellular carcinoma on treatment outcomes in a real-world database.
Authors: Brown Timothy J , Mamtani Ronac , Gimotty Phyllis A. , Karasic Thomas Benjamin , Yang Yu-Xiao 
Published: January 2023

508 Background: Hepatocellular carcinoma (HCC) is a common and deadly form of liver cancer. Systemic therapy with combination atezolizumab and bevacizumab (A/B) is the new treatment standard; yet fewer than 30% experience treatment response. The etiology of HCC (viral, alcohol, or NASH) and its impact on treatment response is unknown. Thus, we sought to determine the impact of etiology on survival outcomes of patients treated with A/B. Methods: This study used the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database. Patients with HCC receiving first-line A/B after January 1, 2020 were eligible for inclusion. We used a validated algorithm to adjudicate cohort by likely etiology (viral, alcohol and NASH). The primary outcome was median real-world overall survival (OS), defined from initial receipt of A/B until death or censored at last receipt of A/B by etiology. The secondary outcome was real-world time to treatment discontinuation (TTD -a validated surrogate that approximates progression-free survival) defined as time from initial receipt of A/B to progression, death, or treatment discontinuation for more than 120 days or censored at last clinical contact by etiology. The Kaplan-Meier method, Cox proportional hazards model and the log-rank test was used to test for differences between etiologies. Results: In total, 429 eligible HCC patients were included (n=216, 50.3% Viral; n=68, 15.8% Alcohol; n=145, 33.8%, NASH). In the total cohort, median OS was 9.4 months (95% CI 7.1-10.9) and median TTD was 5.7 months (5.0-7.0); by etiology, OS medians were 10.1 (7.2-14.0), 9.8 (6.1-13.9), 7.5 (5.3-11.0) months, and TTD medians were 6.1 (5.0-8.0), 5.8 (3.7-7.8), and 5.5 (2.6-7.0) months, for Viral-HCC, Alcohol-HCC, and NASH-HCC respectively. No significant difference in the hazard of death or TTD by etiology were observed in the unadjusted or adjusted Cox regression analyses (see table). The multivariate model included age, ECOG performance status, receipt of prior locoregional therapy, albumin-bilirubin (ALBI) grade, and baseline aspartate aminotransferase. Conclusions: In this large cohort study of US patients with HCC, we did not identify a significant association between etiology and survival or time to treatment discontinuation outcomes, although outcomes were numerically worse in patients with NASH. Although the underlying microenvironment and oncogenesis may differ by etiology, further research is needed to identify those most likely to benefit from A/B. [Table: see text]
Comparison of anti–PD-L1 with anti–PD-1 antibodies in the combination of HAIC and lenvatinib for the treatment of unresectable hepatocellular carcinoma.
Authors: Li Shaohua , Mei Jie , Wang Qiaoxuan , Zhao Rongce , Lu Lianghe , Deng Min , Lin Wenping , Guan Renguo , Wen Yuhua , Zheng Lie , Wei Wei , Guo Rongping 
Published: January 2023

509 Background: Previous study showed the combination of hepatic artery infusion chemotherapy (HAIC), Lenvatinib and immune checkpoint inhibitors (ICIs) makes better overall response rate (ORR) as well as survival benefit than pure systematic treatment for unresectable hepatocellular carcinoma (uHCC). But how to choose different ICIs remains unclear. This study aimed to compare the efficacy and safety of anti-PD-1/PD-L1 antibodies combined with HAIC and Lenvatinib. Methods: This study retrospectively included 184 patients with uHCC treated with HAIC+ Lenvatinib +PD-1/PD-L1 antibody from June 2019 to January 2022 in the liver surgery department of Sun Yat-sen University Cancer Center. We used propensity score match (PSM) to screen and match 60 patients of HAIC+durvalumab+ Lenvatinib (HIL) versus 60 HAIC+PD-1+ Lenvatinib (HPL) to compare the efficacy and safety profile of these two groups. Results: The baseline is basically equilibrium between HIL and HPL group after matching. The median OS and PFS are not evaluable on the data cut-off date Sep 10, 2022. The ORR was higher in the HIL group than in the HPL group according to modified RECIST (mRECIST) (74.1% vs. 53.6%, p = 0.022) and RECIST 1.1 (60.3% vs. 41.1%, p = 0.040) respectively. In addition, 10 (17.2%) patients in the HIL group achieved complete response (CR) while 3 (5.4%) in the HPL group according to mRECIST. The results of subgroup analyses suggested that HIL approach could bring more survival benefits than HPL approach for patients with tumor smaller than 10cm and bilateral liver involvement. The incidence of grades 3 or 4 adverse events (AEs) was 10.0% and 18.3% with HIL and HPL group, respectively. Conclusions: Anti-PD-L1 antibody seems to be a better companion in the combination therapy of HAIC+ICIs+Lenvatinib than anti-PD-1 antibody for higher ORR and lower incidence of severe AEs. Further prospective study including larger population of patients is required.[Table: see text]
Real world data of systemic therapy for hepatocellular carcinoma in Japan: HERITAGE study.
Authors: Asaoka Yoshinari , Tateishi Ryosuke , Yamada Yasuhide , Iijima Hiroko , Kato Naoya , Shimada Mitsuo , Hatano Etsuro , Fukumoto Takumi , Murakami Takamichi , Yano Hirohisa , Yoshimitsu Kengo , Kurosaki Masayuki , Sakamoto Michiie , Matsuyama Yutaka , Kudo Masatoshi , Kokudo Norihiro 
Published: January 2023

510 Background: Currently 6 regimens are available for advanced hepatocellular carcinoma (HCC) in Japan, including atezolizumab plus bevacizumab (AB), sorafenib (S), and lenvatinib (L) for first-line treatment and regorafenib (R), ramucirumab (RAM), and cabozantinib (C) for the second-line treatment. In real-world clinical practice, the number of combinations of treatment sequences is enormous. We have launched a nationwide registry of systemic therapy for HCC named Hepatoma Registry of Integrating and Aggregating Electric Health Records (HERITAGE). Methods: The HERITAGE is linked to the nationwide follow-up survey of the Japan Liver Cancer Association; cases treated with systemic therapy between 2015 and 2022 were included in the current study. Information on treatment efficacy and duration was collected and registered on each treatment regimen. Results: As of June 2022, 6,400 treatment lines (S 2,319, L 2559, AB 768, R 406, RAM 251, C 71) in 4,307 cases were enrolled. The response rates, disease control rates, and median treatment duration of each sequence of regimens are shown in the table. The 1st line regimen, S, L, and AB, were also used as the second and later lines in Japan and found as effective as if used as the 1st line treatment. Limitation: No adjustments for clinical conditions were performed. Conclusions: We have demonstrated the efficacy of various treatment sequences in a sufficient number of cases. Clinical trial information: UMIN000046567 . [Table: see text]
Genomic alterations associated with resistance to EGFR monoclonal antibodies (mAb) in real-world patients with metastatic colorectal cancer (mCRC).
Authors: Klempner Samuel J , C. F. Quintanilha Julia C. F. , Emmett Matthew , Graf Ryon , Schrock Alexa Betzig , Tukachinsky Hanna , Oxnard Geoffrey R. , Myer Parvathi 
Published: January 2023

52 Background: mCRC patients with RAS and BRAF mutant tumors do not benefit from treatment with EGFR mAb. However, some RAS/BRAF wild-type patients do not benefit from EGFR mAbs. We sought to investigate additional primary and acquired biomarkers of resistance to EGFR mAb in mCRC. We hypothesized (1) alterations in pre-specified genes of known biological but unconfirmed clinical significance are associated with less favorable outcomes in patients treated with EGFR mAb; (2) these alterations are acquired during treatment and are associated with the time of exposure to these drugs. Methods: We included mCRC patients with RAS/ BRAF wild-type tumors receiving EGFR mAb (cetuximab or panitumumab) in 1st line (1L, n = 248) or in 2L+ of therapy (n = 2,118). This study used the US-based de-identified Flatiron Health-Foundation Medicine real-world mCRC clinico-genomic database, originating from ~280 US cancer clinics between 01/2011 and 04/2022. Pre-specified genes included PIK3CA, PTEN, MAP2K1, and RTKs. Real-world progression-free survival (rwPFS) and overall survival (rwOS) were compared between patients +/- alterations by Cox models, adjusted for a risk score generated from known clinical prognostic features. Alterations were compared between patients with biopsies collected before and after starting treatment with EGFR mAb by chi-square, adjusted for multiple comparisons. The association between the amount of time on drug exposure and alterations was evaluated by linear regression. Results: Patients with RTK/ MAP2K1 alterations (n = 38, 15.3%) had less favorable outcomes (PFS HR 1.83, 95% CI 1.27-2.65, p = 0.001/ OS HR 1.59, 95% CI 1.00-2.51, p = 0.048). The same trend was observed for patients with PIK3CA/ PTEN alterations (n = 31, 12.5%, PFS HR 1.35, 95% CI 0.89-2.03, p = 0.155/ OS HR 1.75, 95% CI 1.08 -2.85, p = 0.024) and ERBB2amp (n = 21, 8.5%, PFS HR 1.52, 95% CI 0.93-2.5, p = 0.096/ OS HR 1.33, 95% CI 0.71-2.5, p = 0.373). Compared to biopsies obtained before (n = 1,834), those obtained after treatment initiation were enriched for RTK alterations (n = 284, +9%, p = 0.001), especially for METamp (+3%, p = 0.04). Compared to unexposed patients, patients exposed to EGFR inhibitors had higher odds (p < 0.001) of developing RTK alterations (OR: 1.84, 95% CI 1.54-2.19; OR 3.33, 95% CI 2.60-4.24; and OR 2.28, 95% CI 1.56-3.26 for 0-12, 12-24, and 24+ months of exposure, respectively). Additional analyses will be presented. Conclusions: RAS/RAF WT mCRC patients with baseline alterations in RTK genes have less favorable outcomes on EGFR inhibitors (intrinsic resistance), and post-EGFR mAb samples (acquired resistance) converge around RTK and MAPK alterations, particularly MET, in real-world data.
Burden of illness in metastatic colorectal cancer.
Authors: Neuberger Edward , Schwartz Naomi , Hsu Ling-I , Dillon Allison , Siadak Muriel F. 
Published: January 2023

53 Background: Current treatment options for patients with metastatic colorectal cancer (mCRC) have limited efficacy and are associated with substantial toxicity, especially for patients with mCRC refractory to standard therapies. Targeted agents may improve outcomes, compared with traditional chemotherapeutic approaches, in those patients with mCRC expressing actionable biomarkers. The objective of this study was to evaluate clinical outcomes and associated health care costs by line of therapy among patients with mCRC. Methods: A retrospective analysis of Merative MarketScan Commercial and Medicare Supplemental Administrative health claims databases was conducted. Adult patients with mCRC initiating systemic therapy between January 1, 2017 and September 30, 2021 were identified. Patient characteristics, time to discontinuation (TTD), time to next treatment (TTNT), and per-patient-per-month (PPPM) healthcare resource utilization and costs were evaluated for each line of therapy. Results: 3,455 patients with mCRC initiated systemic therapy during the study period and met all patient selection criteria. The median age at index was 56 years and median follow-up was 14 months. 1082 (31%), 372 (11%), and 185 (5%) patients went on to receive 2L, 3L, and 4L+ treatment, respectively. The most common regimens in 1-3L were as follows: 1L – FOLFOX; capecitabine, oxaliplatin; 2L - FOLFIRI+Bev; tipiracil/trifluridine; 3L – tipiracil/trifluridine; regorafenib. Median TTD in 1L through 3L was 22.0, 16.6, and 14.4 weeks, respectively. Median TTNT was 47, 26, and 21 weeks, in 1-3L, respectively. 184 (17%) and 265 (25%) of 2L patients experienced ≥1 inpatient and ≥1 emergency department (ED) visit during 2L treatment, respectively. During 2L treatment, patients had an average of 3.7±7.3 mCRC treatment-related outpatient visits per month. PPPM inpatient, ED, outpatient, and pharmacy costs are displayed. Conclusions: There is an unmet need for effective therapies in 2L+ mCRC, where clinical outcomes are poor. Later lines of therapy are associated with substantial HCRU and costs. [Table: see text]
Characterization of long-term survivors in the TOPAZ-1 study of durvalumab or placebo plus gemcitabine and cisplatin in advanced biliary tract cancer.
Authors: Bouattour Mohamed , Valle Juan W. , Vogel Arndt , Kim Jin Won , Kitano Masayuki , Chen Jen-Shi , Burris III Howard A. , Zaucha Renata , Qin Shukui , Evesque Ludovic , Zhen David Bing , Gupta Vineet Govinda , Park Joon Oh , Żotkiewicz Magdalena , Rokutanda Nana , Cohen Gordon , Oh Do-Youn 
Published: January 2023

531 Background: At the primary analysis of TOPAZ-1 (NCT03875235; data cut-off [DCO] Aug 11, 2021), durvalumab (D) + gemcitabine and cisplatin (GC) significantly improved overall survival (OS) vs placebo (PBO) + GC in participants (pts) with advanced biliary tract cancer (BTC), with OS curves that separated over time (Oh et al. NEJM Evid 2022), that persisted with further follow-up (DCO Feb 25, 2022; HR, 0.76 [95% CI, 0.64–0.91]; 18-month OS, 34.8% [D + GC] vs 24.1% [PBO + GC]; Oh et al. Ann Oncol 2022 Abs 56P). We characterized long-term survivors (LTS) in TOPAZ-1. Methods: Pts untreated for unresectable locally advanced, recurrent or metastatic BTC received D (1500 mg every 3 weeks [Q3W]) or PBO, + G (1000 mg/m2) and C (25 mg/m2) on days 1 and 8 Q3W, up to 8 cycles, followed by D (1500 mg Q4W) or PBO. Characteristics and outcomes of LTS (pts who survived ≥18 months after randomization; DCO Feb 25, 2022) were assessed. Results: There were more LTS with D + GC vs PBO + GC (Table). Characteristics of LTS were consistent with the full analysis set (FAS, all randomized pts) including age, sex, region, primary tumor location, disease classification (metastatic vs locally advanced) and PD-L1 expression. Recurrent disease was more common than initially unresectable disease in LTS vs FAS. Median exposure to study treatment was 11.3 months (mo; D), 9.7 mo (PBO) and 5.5 mo (GC, both arms) in LTS and 7.3 mo (D), 5.8 mo (PBO) and 5.1 mo (GC, both arms) in FAS. The objective response rate in LTS was greater with D + GC vs PBO + GC (44.3%, D + GC; 33.8%, PBO + GC), and greater for both groups vs FAS (26.7%, D + GC; 18.7%, PBO + GC). A higher proportion of LTS in the PBO + GC group received subsequent anticancer therapy, including immunotherapy, than LTS in the D + GC group. The frequency of treatment-related adverse events leading to discontinuation in LTS was consistent with FAS. Conclusions: In TOPAZ-1, characteristics of LTS were generally consistent with the FAS. Overall, LTS were more common with D + GC; LTS in the PBO + GC group appear to be associated with higher frequency of subsequent treatments, including immunotherapy. Clinical trial information: NCT03875235 . [Table: see text]
A multicenter study to investigate the role of sarcopenia as a prognostic factor in patients with hepatocellular carcinoma treated by trans-arterial radioembolization.
Authors: Nam Heechul , Yang Hyun , Seo Yeon Seok , Kim Do Young , Kim Yoon Jun , Bae Si Hyun 
Published: January 2023

532 Background: Trans-arterial radioembolization (TARE) is a form of radiation therapy performed by selective intra-arterial injection of microspheres loaded with Yttrium-90 in hepatocellular carcinoma (HCC). The aim of this study is to identify prognostic factors for overall survival (OS) and progression free survival (PFS) in patients with HCC undergoing TARE. Methods: This is a multi-center retrospective study on consecutive HCC patients undergoing TARE from Jul 2009 to May 2019. Using pre-treatment plain computed tomography imaging, the total cross-sectional area (cm2) of abdominal skeletal muscle at the third lumbar vertebra was measured. The skeletal muscle index (SMI) was calculated by normalizing muscle area to patient height. Results: A total of 347 patients were included in the study (mean age 66 years, 284 male patients). 107 patients (30.8%) had portal vein tumor thrombus (PVTT). 126 patients (36.3%) were classified as sarcopenia. Median 5-year OS was 31.3 months (95% CI 24.7–37.9) and median 12-month PFS was 9.7 months (95% CI 8.0–11.4). Sarcopenia (HR, 1.44; 95% CI, 1.01-2.04, p=0.04), PVTT (HR, 1.70; 95% CI, 1.13-2.56, p=0.01), hypoalbuminemia (≤3.5 g/dL) (HR 1.64; 95% CI 1.17-2.30, p<0.01), and prior treatment experience (HR 1.61; 95% CI 1.00-2.57, p=005) were independently associated with poor 5-year OS by multivariate Cox regression analysis. Sarcopenia, PVTT, multifocal tumor, and prior treatment experience were independent predictors of PFS in multivariate analysis. Conclusions: TARE is an effective therapy for patients with advanced HCC. In patients undergoing TARE, Sarcopenia and PVTT are independent predictors of both OS and PFS.