bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical utility of comprehensive genomic profiling in patients with unresectable primary liver cancer.
Authors: Ishido Shun , Tsuchiya Kaoru , Suzuki Keito , Uchihara Naoki , Tanaka Yuki , Miyamoto Haruka , Yamada Michiko , Keitoku Taisei , Matsumoto Hiroaki , Nobusawa Tsubasa , Higuchi Mayu , Takaura Kenta , Tanaka Shohei , Maeyashiki Chiaki , Tamaki Nobuharu , Yasui Yutaka , Takahashi Yuka , Nakanishi Hiroyuki , Kurosaki Masayuki , Izumi Namiki
Published: January 2023

542

Background: Comprehensive genomic profiling (CGP) using tissue and blood specimens is covered by national health insurance for patients who have already received standard systemic therapy in Japan. We investigated the clinical utility of CGP in patients with unresectable primary liver cancer in real-world practice. Methods: We retrospectively investigated the clinical outcome of the patients with unresectable primary liver cancer. All patients received CGP between February 2021 and May 2022 at our institution. Results: 17 patients with unresectable primary liver cancer were included. 10 patients had hepatocellular carcinoma (HCC) and seven had intrahepatic cholangiocarcinoma (ICC). In HCC patients, the treatment line at CGP was 4th (n=5), 5th (n=4), and 6th-line (n=1). The samples were from liver tumor biopsy (n=2), surgical specimens of bone metastases (n=2), and blood (n=6). Clinically meaningful oncogene mutations were detected in all HCC cases. Seven of 10 patients were candidates for clinical trials, and 1 patient showed TMB-high. Six of the 7 patients could not participate in clinical trials due to renal dysfunction, low platelet counts, the immune-related adverse event of past therapy, or HBV infection. One patient with TMB high started pembrolizumab. In ICC patients, the treatment line at CGP was 1st (n=6), and 2nd -line (n=1). The samples were from liver tumor biopsy (n=5), blood (n=1) and surgical specimens of lung metastases (n=1). Clinically meaningful oncogene mutations were detected in all ICC cases. Six of 7 patients were candidates for clinical trials, and 1 patient showed MSI-high. One patient with MSI high started pembrolizumab, and one patient with FGFR2 fusion could use pemigatinib as 3rd line. The Overall survival duration of this patient with ICC (StageⅣB) was 26 months. In total, 13 of 17 patients were candidates for clinical trials, and 4 of 17 patients could receive personalized therapy according to the results of CGP. Conclusions: CGP in patients with unresectable primary liver cancer was useful in real-world practice. However, most patients could not participate in clinical trials because of adverse events associated with previous therapies. The best timing of CGP should be discussed in the future to provide more personalized therapies.
Bevacizumab combined with atezolizumab or sintilimab as second-line treatment in patients with advanced hepatocellular carcinoma: A retrospective study.
Authors: Gan Leijuan , Li Huikai , Wu Qiang , Li Qiang , Cui Yunlong , Zhang Wei , Fang Feng , Lu Wei , Li Guangtao , Ren Shaohua , Liu Yayue , Lang Mengran , Han Ruyu , Song Tianqiang
Published: January 2023

544

Background: The combination of bevacizumab and immune checkpoint inhibitors (ICI) has demonstrated promising efficacy and safety in the first-line treatment of advanced hepatocellular carcinoma (HCC). However, this combination has not been examined in patients with previous first-line treatment of ICI and tyrosine kinase inhibitor. This study aimed to investigate the effectiveness and safety of bevacizumab combined with atezolizumab or sintilimab as second-line treatment in patients with advanced HCC. Methods: The retrospective study included patients with advanced HCC who received combined therapy of bevacizumab and atezolizumab or sintilimab after failure of lenvatinib plus ICI between July 28, 2020 and March 7, 2022. Baseline patient characteristics were collected. Treatment response, overall response rate (ORR) and disease control rate (DCR) were evaluated according to response evaluation criteria in solid tumors (RECIST) version 1.1. Overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan-Meier method. Treatment-related adverse events were graded according to Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. Results: A total of 20 patients with advanced HCC were included, with a median follow-up time of 11.05 (5.03-20.63) months. Eleven patients died by the last follow-up on August 12, 2022. There were 18 males (90%) and two females (10%). The average age was 59.9±12.08 years. Seven patients (35%) had distant metastasis, and nine (45%) had vascular invasion. Liver function was classified as Child-Pugh grade A in 17 patients (85%) and grade B in three (15%). Patients with Barcelona Clinic Liver Cancer (BCLC) stages B, C and D were 1 (5%), 16 (80%) and 3 (15%), respectively. Eighteen patients (90%) had previous topical therapy. Of all patients previously administered lenvatinib plus ICI as first-line treatment, 14 (70%) had PFS longer than three months. ORR and DCR were 15% (95% confidence interval [CI], 3.2-37.9) and 55% (95% CI, 31.5-76.9), respectively. Median OS was 8.00 months (95% CI, 0.00-16.66), while median PFS was 3.80 months (95% CI, 2.41-5.19). Adverse events were observed in 14 patients (70%). Adverse events of grade 3 or worse occurred in six patients (30%). Conclusions: The combination of bevacizumab with atezolizumab or sintilimab had tolerable safety profile but poor response in the second-line treatment of HCC. Despite the satisfying efficacy as first-line therapy, this combination is not a cost-effective recommendation for advanced HCC cases who failed the first-line treatment of lenvatinib plus ICI. [Table: see text]
Randomized phase 2 study of nivolumab with or without ipilimumab combined with stereotactic body radiotherapy in pretreated patients with metastatic biliary tract cancer.
Authors: Markussen Alice , Johansen Julia S. , Larsen Finn Ole , Theile Susann , Hasselby Jane P. , Willemoe Gro Linno , Lorentzen Torben , Madsen Kasper , Wilken Eva E. , Geertsen Poul F. , Behrens Claus , Svane Inge Marie , Nielsen Dorte , Chen Inna Markovna
Published: January 2023

545

Background: The treatment options for patients with biliary tract cancer (BTC) are limited. The aim of this study was to evaluate the clinical benefit of nivolumab with or without ipilimumab combined with stereotactic body radiotherapy (SBRT) in patients with BTC. Methods: In this phase 2 study with a Simon’s 2-stage optimal design, patients with BTC refractory to at least one line of prior chemotherapy were randomized 1:1 to receive SBRT of 15 Gy combined with nivolumab or nivolumab/ipilimumab stratified by performance status. Signed informed consent was obtained from all patients. The primary endpoint was clinical benefit rate (CBR) defined as the proportion of patients with stable disease, partial response (PR), or complete response according to RECIST 1.1. Decision on expansion independently for both arms was pending on CBR from the first stage. Secondary endpoints included overall response rate, progression-free survival (PFS), overall survival (OS), and safety. Results: Between September 2018 and January 2022, 61 patients (19 SBRT/nivolumab and 42 SBRT/nivolumab/ipilimumab) received at least one treatment. Forty-eight patients (79%) had cholangiocarcinoma (intrahepatic 41, perihilar 2, distal 4, unspecified 1) and 13 patients (21%) had gallbladder cancer. No responses were observed in SBRT/nivolumab arm and this cohort was closed for inclusion after first stage based on CBR of 11% (95% confidence interval (CI) 1-33). SBRT/nivolumab/ipilimumab resulted in CBR of 31% (95% CI 18-47) and an overall response rate of 11.9% (95% CI 4.0-25.6). Of the five patients that achieved a PR, the median duration of response was 4.4 months (95% CI 0.0-9.2). A median PFS of 1.7 months (95% CI 1.6-1.7) and 1.7 months (95% CI 1.6-1.8), and a median OS of 4.7 months (95% CI 3.2-6.2) and 5.0 months (95% CI 2.1-7.9) were observed for patients receiving SBRT/nivolumab and SBRT/nivolumab/ipilimumab, respectively. Treatment-related adverse events grade 3 or higher occurred in 3 (16%) patients in the SBRT/nivolumab arm and 13 (31%) patients in the SBRT/nivolumab/ipilimumab arm. One patient died due to hepatitis in the combination arm. Conclusions: The combination of SBRT/nivolumab/ipilimumab demonstrated anti-tumor activity and acceptable toxicities in patients with advanced BTC. Further studies are warranted. Clinical trial information: NCT02866383 .
Anlotinib plus toripalimab as first-line treatment for patients with unresectable hepatocellular carcinoma: Updated results of the ALTER-H003 trial.
Authors: Lin Haifeng , Ma Jie , Zhuo Manyun , Zhang Chengsheng , Luo Jingru , Zhuang Xiaohong , Zeng Zhiming , Yang Lihua
Published: January 2023

568

Background: Anti-angiogenic plus anti-PD-1/L1 agents have shown superior efficacy over sorafenib in the first-line treatment for uHCC. Anlotinib, a multi-targeted tyrosine kinase inhibitor that targets VEGFR 1/2/3, FGFR 1-4, PDGFR α and β, and c-kit. Toripalimab is a humanized lgG4 mAb against PD-1. Preliminary results exhibited promising efficacy and tolerable safety of the combined regimen. Here we reported the updated results at the data cutoff of August 24, 2022. Methods: This single arm, multicenter, phase II trial of ALTER-H003 was planned to enroll 30 eligible pts to receive anlotinib (12mg, p.o., qd, d1-14, q3w) and toripalimab (240mg, iv, d1, q3w) until disease progression or unacceptable toxicity. Primary endpoint was ORR. Secondary endpoints included PFS, OS, DCR, DoR and safety. Results: From Jan, 2020 to Jul, 2021, 31 pts were enrolled. Pts characteristics were as follows: median age of 56y (range: 27-75); hepatitis B (29, 93.5%); BCLC B/C (23, 74.2%/8, 25.8%); macrovascular invasion (11, 35.5%); extrahepatic metastasis (19, 61.3%) and AFP>400 ng/ml (12, 38.7%). The median follow-up time was 19.9m (95%CI: 14.3–25.5). The confirmed ORR and DCR by mRECIST was 32.3% (95%CI: 14.8-49.7%) and 77.4% (95%CI: 61.8-93.0%), respectively. 10 pts achieved tumor response and the mDOR was 11.1m. The median PFS was 11.0m (95%CI: 3.5-18.4) and the median OS was 18.2m (95%CI: 15.9-20.5). Grade 3-5 treatment-related adverse events (TRAEs) were recorded in 20 pts (64.5%). The common ≥ grade 3 TRAEs included hand-foot skin reaction (3, 9.7%), hypertension (3, 9.7%) and impaired liver function (3, 9.7%). 2 pts had an irTRAE (pneumonitis; impaired liver function) that led to death. Conclusions: Anlotinib plus toripalimab showed hopeful efficacy and manageable toxicity in the first-line treatment for uHCC. Further studies are warranted. Clinical trial information: ChiCTR1900028295 .
The impact of relative dose intensity on overall and progression-free survival during cabozantinib therapy for unresectable hepatocellular carcinoma.
Authors: Nobusawa Tsubasa , Tsuchiya Kaoru , Yasui Yutaka , Uchihara Naoki , Suzuki Keito , Tanaka Yuki , Miyamoto Haruka , Ishido Shun , Yamada Michiko , Keitoku Taisei , Matsumoto Hiroaki , Higuchi Mayu , Takaura Kenta , Tanaka Shohei , Maeyashiki Chiaki , Tamaki Nobuharu , Nakanishi Hiroyuki , Kurosaki Masayuki , Izumi Namiki
Published: January 2023

569

Background: Cabozantinib (CAB) has been approved as 2nd or later-line worldwide in patients with unresectable hepatocellular carcinoma (u-HCC). There is no data about the relationship between the relative dose intensity (RDI) of CAB and clinical outcome. We investigated the impact of RDI on overall survival (OS) and progression-free survival (PFS) during CAB in real-world practice. Methods: A total of 38 u-HCC patients who received CAB between Jan 2021 and Sep 2022 at our institution were enrolled. Tumor assessments in accordance with RECIST ver1.1 were done using dynamic CT or MRI within 4-8 weeks and every 8-10 weeks thereafter. The RDI of CAB for the first month (1M-RDI) was calculated. Results: The median age was 74 years, and 30 patients were Child-Pugh A. BCLC stage A/B/C were 0/ 11/ 27 patients, and 34 patients were previously received atezolizumab plus bevacizumab. As 2nd or 3rd-line, 20 patients received CAB. The median follow-up duration was 7.2 months, and the median PFS was 4.4 months in all patients. The median overall survival (OS) was 16.2 months from the administration of CAB. The objective response rate (ORR) and disease control rate (DCR) was 13.8% and 89.7%. Adverse events (AEs) were observed in all patients, requiring dose reduction in 26 patients (68%) and interruption of CAB in 21 patients (55%). The median 1M-RDI was 35%, and there was no significant difference in PFS between 1M-RDI ≧40% (high 1M-RDI, n=13) and <40% (n=16) (4.1 months vs. 4.7 months, p=0.89). There were no significant differences in age, pretreatment ALBI score, AFP, and major vascular invasion (MVI) between the patients with and without a high RDI. The induction rate of molecular targeted therapies after CAB was 60%. The only significant factor associated with PFS was MVI (HR 0.10, 95%CI 0.02-0.65, p=0.02). In a multivariate analysis, pretreatment ALBI score (HR 5.8, 95% CI 1.2-27.8, P=0.03) and hypertension as AE during CAB (HR 0.29, 95% CI 0.09-0.87, P=0.03) were the significant factors associated with OS. Conclusions: Maintaining a high 1M-RDI of CAB was not associated with OS and PFS in real-world practice. Dose modification is essential for CAB therapy in u-HCC patients.
Real-world assessment of treatment sequencing of patients with advanced biliary tract cancer in a private practice in Rio de Janeiro and São Paulo, Brazil.
Authors: Carvalho Ligia , Almeida Kaique Ferreira Costa de , Saldanha Lais , Beck Kelly de Paula , Victorino Ana Paula
Published: January 2023

587

Background: Biliary tract cancer, including cholangiocarcinoma and gallbladder carcinoma, have low incidence and poor prognosis. Despite representing a heterogeneous group, the studies encompass these malignancies as the same entity. There are few phase III trials that evaluate treatment sequencing in the metastatic setting. The ABC 02 trial showed an increase in overall survival (OS) with Gemcitabine and Cisplatin (GemCis) in first line and the ABC 06 trial an increase in OS in second-line Folfox. Recently, the TOPAZ 1 trial demonstrated benefit of first-line immunotherapy. The primary objective of this study was OS in patients with advanced cholangiocarcinoma according to treatment. The secondary objective was to analyze the patients characteristics. Methods: Retrospective analysis of medical records from two private institutions. Patients were eligible if they had advanced intra or extra cholangiocarcinoma or gallbladder carcinoma, undergoing chemotherapy from January of 2015 to January of 2021. Results: Database included 82 patients with intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma or gallbladder carcinoma, 54%, 23% and 23%, respectively. Median age was 65 years old, with an equal proportion between sexes. 75% had metastasis at diagnosis and 12 patients (14%) underwent more than two lines of treatment. Median OS was 288 days. GemCis was the most common first line protocol (62%), followed by Gemcitabine and Oxaliplatin (17%). There was no difference in OS between the regimens, regardless of the primary site. Folfiri and Folfox were used in the same proportion in second line (17% for each), but with a significant increase in OS for Folfiri (485 days vs. 368 days, p=0.02), regardless of the primary site. According to univariate analysis of factors associated with mortality, the significant variables were: surgery for primary site (HR 0.49 [95% CI 0.28-0.85]; p=0.01), metastasis at diagnosis (HR 1.89 [95% CI 1.10-3.25]; p=0.02), liver metastasis at diagnosis (HR 1.69 [95% CI 1.02-2.80]; p=0.04), and more than two lines of treatment (HR 0.41 [95% CI 0.21-0.80]; p=0.009). Conclusions: Despite being retrospective and not using first-line immunotherapy, this study was able to demonstrate no difference in OS between first-line regimens with GemCis or Gemcitabine and Oxaliplatin. However, when analyzing second-line sequencing, Folfiri demonstrated benefit independent of the primary site.
Responses to first-line systemic therapies in patients with hepatocellular carcinoma with TERT promoter mutations.
Authors: Chang Jeremy , Fowler Kathryn J , Tamayo Pablo , Burgoyne Adam
Published: January 2023

589

Background: The treatment landscape of advanced hepatocellular carcinoma (HCC) has made significant advances with the use of oral multikinase inhibitors and immunotherapy-containing regimens. However, there is minimal data with regards to which biomarkers may predict treatment responses in this population. The increased use of next-generation sequencing (NGS) has identified the most frequent mutations in HCC, including TERT promoter mutations which are found in up to 65% of patients. With the high frequency of these mutations, additional studies are needed to investigate their associations with treatment outcomes. Methods: Our team performed a retrospective study to determine the association between TERT promoter mutations in HCC and responses to first-line systemic therapies. All patients in this study underwent NGS testing on tumor tissue or peripheral blood samples. Responses to treatment were determined by imaging at least 6 weeks after the start of systemic therapy. Results: There were 128 HCC patients included in this study with TERT promoter mutations found in 72 patients (56.3%). All patients received first-line therapy with either an immunotherapy-based regimen or oral multikinase inhibitor monotherapy (lenvatinib or sorafenib). When looking at responses to all first-line therapies, patients with TERT promoter mutations were found to have significantly higher rates of disease progression (PD) compared to those without TERT promoter mutations (34.7% vs 17.9%, p = 0.04). In addition, when stratifying responses by type of systemic therapy, the TERT promoter-mutated population had notably higher rates of PD with immunotherapy regimens compared to patients without TERT mutations (34.6% vs 10.8%, p = 0.01). In contrast, there was no significant difference in rates of PD with oral multikinase inhibitor monotherapy between TERT mutated and TERT non-mutated individuals (35% vs 31.6%, p = 1). See table for further details. Conclusions: In this study, HCC patients with TERT promoter mutations were found to have significantly higher rates of PD to first-line therapies and, specifically, immunotherapy-containing regimens. Given the prevalence of these mutations in the HCC population, further investigation is needed to clarify this association and its impact on patient survival.[Table: see text]
Significance of alterations in DNA damage repair (DDR) genes in advanced biliary cancers (ABCs) treated with second-line active-symptom-control (ASC) alone or ASC with oxaliplatin/5-FU chemotherapy (ASC+FOLFOX) in the randomised phase III, multicentre, open-label ABC-06 trial.
Authors: Lamarca Angela , Palmer Daniel H. , Wasan Harpreet Singh , Ross Paul J. , Ma Yuk Ting , Arora Arvind , Falk Stephen , Gillmore Roopinder , Wadsley Jonathan , Patel Kinnari , Anthoney Alan , Maraveyas Anthony , Hobbs Claire , Wilkinson Lorna , Macdonald Timothy , Hartley Claire , Ryder David , Bridgewater John A. , Valle Juan W. ,   Advanced Biliary Cancer (ABC) Working Group
Published: January 2023

593

Background: The ABC-06 clinical trial established ASC+mFOLFOX as the standard of care treatment after Cisplatin and Gemcitabine (CisGem) for ABC. Translational research explored the role of alterations in DDR-related genes in the context of the ABC-06 clinical trial. Methods: Translational research using samples collected from the ABC-06 trial included all recruited patients with tissue sample containing >20% tumour cellularity with sufficient DNA extracted for analysis. Primary objective: assess the prevalence of somatic mutations within DDR genes in ABC. Secondary objectives: explore the impact of somatic mutations in DDR genes on: A) Patient’s response to platinum-based chemotherapy (predictive biomarker): 1) Retrospectively, using progression-free survival (PFS) data from 1st-line chemotherapy and 2) Prospectively, by assessing the impact on PFS/radiological response to 2nd-line FOLFOX (vs. control) and B) Overall survival (prognostic biomarker). Survival analysis was performed with Kaplan-Meier and Cox Regression. Results: Of 162 pts randomised, 83 had a sample available for analysis; of these, analysis failed in 24 despite >20% tumour content. Thus, a total of 59 patients (30 ASC arm, 29 ASC+FOLFOX arm) were eligible for this translational analysis: male 50.85%, metastatic 77.97%, intrahepatic cholangiocarcinoma 47.46%, adenocarcinoma 91.53%, median age 65.84 years (95% CI 63.36-68.91). Pathogenic mutations in DDR genes were identified in 22 patients (37.29%). PFS did not vary depending on the DDR-gene alterations either in the first-line setting with CisGem (n=59; 8.73 months vs 8.18 months; p-value 0.155) or with second-line FOLFOX (n=29; 3.19 months vs 3.45 months; p-value 0.098). Median OS for DDR-altered patients was 4.59 months (95% CI 2.17-5.88) (vs 7.23 months (95% CI 5.45-8.28) for DDR-wild-type); HR 2.63 (95% CI 1.48-4.67); p-value 0.001. This prognostic impact was confirmed when the prognostic model was adjusted for treatment arm and stratification factors (HR 3.75 (95% CI 1.99-7.09); p-value <0.001). Conclusions: For ABC patients, the presence of DDR-related gene pathogenic mutations are present in around one third of patients. Despite presence of DDR-mutations having a negative prognostic impact, their predictive role is not confirmed either for first-line CisGem or second-line FOLFOX. Clinical trial information: NCT01926236 .
Detection of DNA adduct γ-OHPdG in circulating tumor cells (CTCs) and its use as a prognostic biomarker in patients with hepatocellular carcinoma (HCC).
Authors: He Aiwu Ruth , Chung Fung-Lung , Aggarwal Monika , Zhu Zizhao , Gould Sophie , Zhang Kevin , Kuo Mark , Johnson Peter , Beheshtian Samira , Kuhlman Laura , Zhao Zijun , Fang Hongbin , Kallakury Bhaskar , Creswell Karen , Kroemer Alexander
Published: January 2023

594

Background: A blood-based biomarker to predict the risk of hepatocellular carcinoma (HCC), and its recurrence is needed. Previously, we showed that γ-OHPdG, a mutagenic DNA adduct formed by lipid peroxidation, in liver biopsies from HCC patients, as detected by IHC, is inversely associated with overall survival (p<0.0001) and recurrence-free survival (p<0.007) after surgical resection. This finding suggests that γ-OHPdG may serve as a prognostic biomarker of HCC and its recurrence. A non-invasive method to detect γ-OHPdG is needed. Liquid biopsy is preferred over tissue biopsy because it is non-invasive, allows repeated sampling, lower risk to patient, and lower medical care cost. We developed a non-invasive method for detecting and quantifying γ-OHPdG using CTCs from HCC patient. Methods: The method involved following steps. First, CTCs from blood samples were isolated using a RosetteSep CD45 Depletion Cocktail and Ficoll Paque-based method. Isolated cells were identified as liver CTCs using asialoglycoprotein receptor 1 (ASGPR1), a cell surface protein expressed solely on the surface of hepatic cells, and γ-OHPdG by immunocytochemistry. The percentage of ASGPR1 and γ-OHPdG-positive stained CTCs and γ-OHPdG staining intensity was quantified using Metamorph software. The staining intensities in livers CTCs will be compared with that found in liver biopsies by IHC. Results: To determine the sensitivity and specificity of testing -γ-OHPdG level in circulating tumor cells using an-anti γ-OHPdG antibody, we showed that the proportion of γ-OHPdG-positively stained cells and staining intensity increased in HepG2 liver cancer cells upon acrolein treatment at increasing concentration. Furthermore, when the HepG2 was used to spike blood of healthy volunteers’, the recovery rate of γ-OHPdG positivity was > 50-60%. CTCs from 32 HCC patients, detected at a positivity rate of ~97%, were tested for γ-OHPdG levels using the method developed in this project. The clinical factors including demographics, risk factors, alpha-fetoprotein (AFP), HCC size, multifocality, vascular invasion, extrahepatic metastasis have been correlated with the levels of γ-OHPdG in CTCs. Conclusions: The CTC method developed for detecting and quantifying γ-OHPdG warrant validations as a prognostic biomarker for predicting HCC risk and recurrence in clinical trials.
Psychosocial, behavioral, and communication factors associated with completion of the mt-sDNA test for colorectal cancer screening.
Authors: Alam Shama , Zhu Xuan , Squiers Linda , Helmueller Leah , Madson Gabriel , Southwell Brian , Gates Carlye , Kneedler Bonny , Limburg Paul J. , Finney Rutten Lila J
Published: January 2023

60

Background: Colorectal cancer (CRC) screening has been shown to reduce CRC incidence and mortality. Several CRC screening modalities are guideline recommended for average-risk adults aged 45-75 years. CRC screening is underutilized in the US and access to facility-based options, such as colonoscopy, represents a potential barrier. Home-based stool tests are guideline-endorsed and offer a convenient, accessible, scalable option for CRC screening. Thus, understanding the factors that influence completion of stool-based CRC screening is important to guide interventions to improve adherence. We developed a survey, informed by behavioral theory, to identify psychosocial, behavioral and communication factors associated with completion of mt-sDNA screening. Methods: The survey instrument was finalized through expert review, quality testing, and cognitive testing. Adults aged 45-75 years, with a US postal address, who received a valid order for mt-sDNA and whose kit was shipped between 5/21-9/21 were eligible for sampling. RTI administered the survey between 3/22-6/22. Participants had the option to complete electronic or paper surveys. We fit a multivariable logistic regression to identify factors significantly associated with mt-sDNA test completion. Results: Of 17,370 individuals invited to participate, 2,973 completed the survey (AAPOR RR3 = 21.7%); 77.3% of the sample completed the mt-sDNA test. Responders and non-responders did not differ significantly by sex or age. Controlling for demographic characteristics and insurance status, the odds of mt-sDNA test completion were significantly higher among participants who reported greater perceived test effectiveness (OR = 1.20), greater ease (OR = 4.06), and greater comfort in test use (OR = 1.18). Odds of test completion were significantly higher among participants who reported their healthcare provider discussed the mt-sDNA test with them (OR = 2.01) and involved them a great deal in decision making about CRC screening (OR = 1.29). Participants who expressed greater worry about developing CRC were less likely to return their mt-sDNA kit (OR = 0.81). Conclusions: To improve population adherence to CRC screening recommendations, efforts are needed to ensure patients understand the attributes and effectiveness of available test options and feel adequately prepared to complete their preferred screening test. Additionally, healthcare providers must be appropriately prepared and resourced to educate and to engage patients in shared decision-making about CRC screening.
Artificial intelligence (AI)-powered immune phenotyping to predict outcomes of immuno-oncology (IO)-based regimens in hepatocellular carcinoma (HCC).
Authors: Chon Hongjae , Kim Chan , Kang Beodeul , Cheon Jaekyung , Kim Gwangil , Oum Chiyoon , Kim Seulki , Park Gahee , Mostafavi Mohammad , Kang Mingu , Ock Chan-Young
Published: January 2023

601

Background: Anti-PD-(L)1 monotherapy or combination with bevacizumab or ipilimumab are approved treatment options in HCC. Nevertheless, not all patients benefit from IO treatment, and discovery of predictive biomarkers for IO outcome has not been fully investigated. Immune phenotype analysis by AI-powered spatial tumor-infiltrating lymphocyte (TIL) analyzer in H&E whole-slide images (WSI), Lunit SCOPE IO, has shown predictive effect across multiple cancer types. Here, we investigated the correlation between immune phenotype (IP) and the real-world outcomes in HCC. Methods: Real-world dataset of 177 patients with HCC were retrospectively collected from CHA Bundang Medical Center. Inflamed score was defined by the proportion of area with high intra-tumoral TIL density per 0.5 mm2-sized grid. IP status was sub-analyzed by PD-L1 combined positive score (CPS) and prognostic factors including Child-Pugh class and Barcelona Clinic Liver Cancer (BCLC) stage. We evaluated the correlation between IP and IO outcome by regimen (atezolizumab+bevacizumab [Atez+Bev], n=100; nivolumab+/-ipilimumab [Niv+/-Ipi], n=77). Results: The majority of patients (75.3%) were Child-Pugh class A (75.3%) and BCLC stage C (86.5%), respectively. Atez+Bev was mostly received as first-line therapy (92.0%), whereas Niv+/-Ipi as second-line or beyond (98.7%). The inflamed score was significantly higher in patients who had lymph node metastasis ( p=0.008), but it was not correlated with other metastatic sites, or any other prognostic factors. Of 177 patients, 105 (59.3%) patients were classified as having a high inflamed score (≥10%) and 72 (40.7%) patients as having lower than 10%. PD-L1 CPS was significantly higher in the sample with high score compared to those with low inflamed score ( p=0.01387). PFS of Niv+/-Ipi were significantly favorable in the patients with high inflamed score (3-m PFS rate; 44.0% vs 3.61%, 12-m PFS rate; 17.8% vs 0%, Hazard ratio [HR] 0.37, 95% confidence interval [CI] 0.22-0.63, p<0.001), while PFS of Atez+Bev were not different according to inflamed score (3-m PFS rate; 67.5% vs 57.3%, 12-m PFS rate; 36.6% vs 31.0%, HR 0.80, 95% CI 0.48-1.32, p=0.400). Conclusions: Inflamed score, the proportion of area with high intra-tumoral TIL infiltration, can be a clinically significant predictor of PFS of Niv+/-Ipi, but it was not relevant for Atez+Bev treatment outcomes.
The impact of viral etiology in yttrium-90–treated hepatocellular carcinoma.
Authors: Naveh-Benjamin Itamar Marie , Jin Ruyun , Romano Kara D , Le Tri Minh , Kunk Paul Raymond , Reilley Matthew , Read Paul , Janowski Einsley-Marie
Published: January 2023

608

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer and is derived from a background of chronic inflammation from both viral and environmental factors. Recent data indicates that immune therapy efficacy is improved in virally mediated HCC. We sought to investigate what impact HCC etiology has on outcomes in patients treated with yttrium-90 (Y90). Methods: We conducted a retrospective review of patients with HCC treated at our institution with Y90 radiotherapy from 2005-2021. Clinical and treatment characteristics were recorded, including: age, stage, HCC etiology, performance status, Child Pugh class, liver mass/volume treated, dose, prior therapy, imaging characteristics and basic labs. Univariable (UVA) and multivariable analyses (MVA) were conducted to identify prognostic factors for local control (LC) and overall survival (OS) following Y90. Results: 67 patients and 196 distinct tumors treated with Y90 were identified. Median prescription dose was 110 Gy (range 44-157). Patients were stage I-IVB with the most frequent stages being II, IIIb and IIIa (34%, 21% and 19% patients, respectively). 49 patients (73%) were Child-Pugh A and 18 (27%) were Child-Pugh B. 5 patients only had hepatitis B (7%), 26 patients only had hepatitis C (39%), and 6 patients had both hepatitis B and C (9%). Median OS among all patients was 7.6 (95% CI 5.6-11.5) months following Y90. The LC rate of all treated lesions was 42% and 24% at 6 and 12 months, respectively. On UVA analysis, improved LC was associated with younger age ( p=0.019), smaller liver mass ( p=0.039), and Hepatitis B etiology ( p=0.018). On Cox regression survival analysis, worsened OS was associated with lower ECOG status ( p=0.024), advanced stage ( p=0.023), lower albumin ( p=0.001), higher AFP ( p<0.001), and portal vein invasion/thrombosis ( p=0.006, p=0.010). On MVA, lower albumin, higher AFP, advance stage and prior sorafenib were significantly related to worsened OS. If hepatitis B or C was forced into the MVA, the hazard ratio was 0.6 (95% CI 0.3-1.04) with p=0.068. Conclusions: Our results indicate that viral etiology impacts LC in our patients. Larger studies are necessary to confirm these results and to determine whether viral etiology impacts OS.
Association of awareness and use of patient navigation services for colorectal cancer screening with test completion and likelihood of future use.
Authors: Alam Shama , Zhu Xuan , Squiers Linda , Helmueller Leah , Madson Gabriel , Southwell Brian , Gates Carlye , Kneedler Bonny , Limburg Paul J. , Finney Rutten Lila J
Published: January 2023

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Background: Although several guideline-recommended colorectal cancer (CRC) screening modalities have been shown to reduce CRC incidence and mortality, adherence remains below U.S. public health goals. Patient navigation services have been shown to improve CRC screening completion. Patient navigation services, including outbound phone, text, and e-mail reminders, and inbound phone support (>200 languages) are included with all mt-sDNA test (Cologuard) orders. A website and financial assistance (upon request and qualification) are also available for patients. We developed a survey, informed by behavioral theory, to identify psychosocial and communication factors associated with completion of mt-sDNA screening including questions to evaluate awareness and use of navigation services. Methods: Adults aged 45-75 years, with a US postal address, who received a valid order for mt-sDNA screening between 5/21-9/21 were eligible for sampling. RTI administered the survey between 3/22-6/22. Participants had the option to complete electronic- or paper-based surveys. We conducted crosstabulation with Chi Square to assess whether awareness and use of navigation services was significantly associated with (a) test completion within 6 months of the order date and (b) likelihood of future mt-sDNA use. Results: 2,973 participants completed the survey (RR= 21.7%; 65.15% by web and 34.85% by paper). Responders and non-responders did not differ significantly by age or sex. For each navigation service, awareness was significantly higher among those who completed the mt-sDNA test compared to those did not. Across all services, awareness was significantly higher among respondents reporting they were ‘very likely’ to complete mt-sDNA if recommended by a healthcare provider in the future than all other responses combined. A significantly higher proportion of completers (vs. non-completers) reported receiving the email reminder, using the Cologuard website, and using the English language inbound phone support. A significantly higher proportion of those “very likely” to complete mt-sDNA screening in the future reported receiving the email reminder, using the Cologuard website, and using the English language inbound phone support. Conclusions: Awareness and use of patient navigation services was associated with higher completion of the mt-sDNA test and with greater likelihood of future mt-sDNA test use. Patient navigation services comprised of evidence-based strategies, such as reminders, support patient adherence to CRC screening.
Overall survival (OS) in gastrointestinal (GI) neuroendocrine tumors (NETs) based on primary site, stage, and surgery.
Authors: Laderian Bahar , Farha Nicole , Mundi Prabhjot Singh , Wei Wei , Khorana Alok A. , Kim Michelle Kang , Steele Scott , Gorgun Emre , Fojo Antonio Tito , Krishnamurthi Smitha S.
Published: January 2023

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Background: There are limited data on the impact of primary site and surgical intervention on long-term outcomes in GI-NETs. We hypothesized that primary site would be associated with differences in stage-specific OS. Methods: In the National Cancer DataBase, using histology codes, we identified 124,081 GI-NETs diagnosed between 2004-2019 in individuals 18 years or older. OS was estimated by the Kaplan-Meier method. Differences in survival based on primary site, stage, and surgical intervention were assessed using a Cox proportional hazards model, accounting for multiple comorbidities, e.g. Charlson-Deyo Comorbidity Index. Results: The most common primary site for GI-NETs was small intestine (33.6%), followed by colon, rectum, pancreas, and stomach comprising 19.8%, 17.5%, 15.5%, and 9.2%, respectively. Patients with stage I-III NETs undergoing surgery had significantly better median OS compared to those without surgery (mOS 197 vs 115 mo., p<0.0001 by log rank test). Patients with stage IV NETs undergoing primary resection also had improved mOS vs those with no surgery (125 vs 54 mo., p<0.0001). For stage I-III patients without surgery, 2-yr and 5-yr survival rates were highest in the rectum and lowest in small intestine ( p<0.0001). Among those with stage I-III with surgery, 2-yr and 5-yr survival rates were also highest in the rectum, and lowest in the biliary system at 89% and 82% ( p<0.0001). In contrast, for stage IV patients without primary resection, 2-yr and 5-yr survival rates were highest among small intestine and lowest in the rectum ( p<0.0001). Among those who had primary tumor resection, 2-yr and 5-yr survival rates were highest in pancreas and lowest in colon at 2 yrs and rectum at 5 yrs ( p<0.0001). Conclusions: Surgical intervention for GI-NETs is associated with improved OS in both localized and stage IV disease, with consistent trends across different primary sites. Primary tumor resection was associated with the largest increase in 5-yr survival for stage IV NETs arising from pancreas and stomach. Patient selection for surgery undoubtedly contributed to the improved OS, but resection of primary tumors in stage IV GI-NETs may have a disease modifying effect. Further study is warranted with more granular data to identify patients with stage IV GI-NETs who may benefit from primary tumor resection.[Table: see text]
Clinical outcomes in patients with microsatellite instability-high (MSI-H) metastatic colorectal cancer (mCRC) in the pre-immunotherapy era.
Authors: Zwart Koen , van der Baan Frederieke , Dixon Matthew , Frantz Bryan , Punt Cornelis J. A. , Koopman Miriam , Vink Geraldine R. , Roodhart Jeanine
Published: January 2023

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Background: Data on clinical treatment outcomes of systemic non-immunotherapy in patients with MSI-H mCRC are limited due to low incidence. Real world data can support the interpretation of immunotherapy studies. Our aim is to provide insight on clinical outcomes of patients with MSI-H mCRC treated with systemic non-immunotherapy. Methods: We describe an observational cohort study with real-world data from the Netherlands Cancer Registry during 2015-2018 (N=383) and trial-based data from three prospective phase III first-line clinical trials: CAIRO, CAIRO2 and CAIRO3 (N=54). We investigated progression free survival (PFS) and overall survival (OS), which were defined as time from the start of first-line (PFS1/OS1), second-line (PFS2/OS2) and third-line (PFS3/OS3) of systemic non-immunotherapy until disease progression or death, respectively. Furthermore, we investigated objective response rate (ORR), which was defined as the proportion of patients with a complete or partial response as best response after first-line (ORR1), second-line (ORR2) and third-line (ORR3). Results: A total of 437 patients with MSI-H mCRC were analyzed. The proportion of patients receiving at least one line of systemic non-immunotherapy was 63%, 21% received two lines, and 5% received three lines. Patients receiving one line of therapy (N=270) had a median age of 69, 50% were female, 49% had a WHO performance score of 0, 70% had a right-sided tumor, 72% had synchronous mCRC, and 64% of those with synchronous mCRC received primary tumor resection. When known, 52% of patients harbored a BRAF mutation and 21% a RAS mutation. The results of OS, PFS, and ORR are summarized. Conclusions: To our knowledge these results provide insight on clinical outcomes in the largest observational cohort of patients with MSI-H mCRC treated with systemic non-immunotherapy to date. We showed a median PFS1 of 5.9 months and an OS1 of 14.1 months, which are in distinct contrast with patients in MSI-H mCRC trials receiving mono-immunotherapy in which a median PFS1 of 16.5 months was reached and a median OS1 was not reached after median follow-up of 44.5 months. Only 21% of patients in our observational cohort reached second-line of systemic non-immunotherapy and 5% third-line. Our results underline the importance and early access to immunotherapy in the MSI-H mCRC population. [Table: see text]
Democratizing access to research for patients with pancreatic cancer across a diverse health system through natural language processing of radiology reports.
Authors: King Daniel , Valente Cristina , Barish Matthew , Carvino Anthony
Published: January 2023

664

Background: Access to clinical trials and translational research studies is integral to improving cancer care for pancreatic cancer. The in-patient setting is a valuable opportunity to obtain research specimens and establish transition to out-patient oncology. However, samples coordinators rarely have sufficient lead time prior to biopsy to consent patients and be present for tissue collection. Meanwhile, histopathology of biopsied specimens may not be complete prior to discharge, hindering follow-up planning. Polyethnic-1000 is a research study enrolling African American patients with pancreatic cancer, is a priority study for our institution, and was the target study that motivated the below innovative strategy to better obtain research samples and ensure adequate follow-up. Methods: We observed recurrent suspicious abnormalities on abdominal radiology reports that foreshadow subsequent biopsy of the pancreas. To explore this further, we trained a natural language classifier to identify radiology reports as suspicious for pancreatic cancer. The pretrained model used is RadBERT, a custom-built language model based on Google’s BERT and further pretrained on several million radiology text reports. A gastrointestinal oncologist, clinical research coordinator, and radiologist informatician curated a dataset consisting of 1136 CT abdominal radiology reports, among which 696 were considered suspicious for pancreatic cancer. Among this curated database of reports, a training set consisting of 908 reports was used to fine-tune the RadBERT base model and produce our pancreatic cancer suspicion classifier. A validation and test dataset each consisting of 114 cases were reserved for model evaluation. We computed the final classifier performance metrics over the test dataset. Results: The model obtained an accuracy of 92%, and produced an F1 score of 0.936, a recall of 0.943, and a precision of 0.930. Conclusions: An early iteration model to classify CT abdominal radiology reports was highly accurate and has the potential to substantially increase identification of patients who may be suitable for clinical research studies and trials. We are now working to improve and expand our dataset in order to train classifiers with greater and more robust performance, while simultaneously developing an automated near real-time process that will leverage our models to identify reports suspicious for pancreatic cancer and then notify a coordinator and navigator.
Impact of COVID-19 pandemic on pancreatic cancer disparities and outcomes in Florida.
Authors: Lim Alexander , Telisnor Guettchina , Zhang Zhongyue , Lou XiangYang , Nassour Ibrahim , Salloum Ramzi , Rogers Sherise C.
Published: January 2023

667

Background: Pancreatic cancer (PDAC) is the third-leading cause of cancer death in the United States. Florida had a high infection rate with several peaks throughout 2020 and 2021. The first aim of this study is to evaluate the impact of the COVID-19 pandemic on survival time, rate of surgical resection, and time to treatment of newly diagnosed pancreatic cancer in Florida. The second aim was to assess whether disparities with respect to race, age, income, and gender were exacerbated in newly diagnosed pancreatic cancer via stratified analysis of pandemic groups. Methods: This retrospective study included patients identified by OneFlorida+ Clinical Research Network, a statewide data trust, who were newly diagnosed with pancreatic adenocarcinoma via ICD 10 coding from January 1st, 2017 to October 31st, 2020. Patients were compared between 3 cohorts based on date of pancreatic cancer diagnosis: pre-pandemic (01/01/2017- 09/30/2019), transition (10/01/2019-02/28/2020), and pandemic (03/1/2020-10/31/2020). Patients with a diagnosis of neuroendocrine carcinoma were excluded. Results: 934 unique patients were identified for analysis, of whom 81.3% were in the pre-pandemic cohort, 8.2% in the transition cohort, and 10.5% in the pandemic cohort. The racial distribution was 19.4% African American, 70.2% Caucasian, 0.7% Asian, 8.2% of Other races, and 1.3% reported unknown race or refused to answer. The median age was 67 years (range, 27–89 years). Gender was even. The median income was $52,915 (range, $23,704–$124,821). The differences in overall survival were not significant for age and gender across the 3 groups. Patients with income <$53,000 had significantly lower survival time across all groups. African Americans had significantly lower survival time in the pre-pandemic and transition cohort (p< .005), but Caucasians had the lowest survival time for the pandemic group (p <.005). 60.2% of early-stage patients did not have surgery and the group distribution was 64.2% pre-pandemic, 48.5% transition, and 44.4% pandemic (p< 0.027). Time to treatment was not significant across all groups and demographics. Conclusions: This study found a decrease in diagnosis, survival rate for some groups, and surgical resection rates during the COVID-19 pandemic in Florida. Resource planning should target these disparities in income and race.[Table: see text]
Does distance traveled impact management and outcomes in patients with pancreatic adenocarcinoma who are candidates for curative resection?
Authors: Khan Mariam , Backer Grant , Alvarado Andrew , Wang Susanna , Devireddy Deepthi , Parker Jessica , Assifi M Mura , Chung Mathew , Wright G Paul , Chandana Sreenivasa R
Published: January 2023

668

Background: We investigated the impact of distance traveled to a tertiary care center for treatment in the management and outcomes of patients with pancreatic adenocarcinoma (PDAC). Methods: Patients treated for operable PDAC at a single institution from 2010-2019 were retrospectively reviewed. Data was collected on demographics, tumor characteristics, social determinants of health, diagnostic/staging work-up, surgical details, and outcomes. Patients were divided into three groups based on distance from our institution: Group A, <10 miles, Group B, >11-50 miles, or Group C, > 50 miles. The primary outcome was two-year survival. Results: There were 314 patients included. The mean age was 67.6+10.5 years. Patients farther from the hospital were less likely to undergo CT with contrast (Group B 97.1% versus Group C 89.0%, p = 0.02) and more likely to get MRCP (Group A 17.0% versus Group C 36.3%, p = 0.01) for staging. Distance was also associated with increased time to first encounter with medical or surgical oncology (Group A 6 days versus Group C 9 days, p = 0.02) and treatment initiation (Group A 22 days versus Group C 28 days, p < 0.001). There were no differences in postoperative complications, length of stay, discharge disposition, or follow-up. Two-year survival was better in Group A than Group B (54.1% versus 35.5%, p = 0.04). There was no difference in five-year survival. In the multivariable model for two-year survival, no patient or tumor characteristics were significant. Conclusions: In this PDAC population, patients living farther from a tertiary cancer center had worse two-year postoperative survival. Prospective studies in this area are needed.