bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

61 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.