bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II clinical trial to study the use of cabozantinib (cabo) in patients with hepatocellular carcinoma (HCC) post immunotherapy treatment.
Authors: Chan Stephen Lam , Ryoo Baek-Yeol , Mo Frankie , Cheon Jaekyung , Li Leung , Wong Kwan H. , Yim Nicole , Kim Hyeyeong , Yoo Changhoon 
Published: January 2023

571 Background: There has been a lack of prospective clinical trial data on subsequent treatment after immune checkpoint inhibitor (ICI)-based treatment in HCC. To address this question, we designed and completed a phase II multicentred study to evaluate the use of cabo in HCC after prior ICI-based treatment. Methods: This is an investigator-initiated clinical trial involving 3 academic centres in Hong Kong and Korea. Key eligibility criteria include confirmed diagnosis of HCC; refractoriness to prior ICI-based treatment; duration of prior ICI-based treatment ≥2 months; Child's A liver function; ECOG performance status 0-2; maximal 2 lines of therapy. All patients (pts) were started cabo at 60mg once daily to progressive disease or intolerable toxicity. The primary endpoint is progression-free survival (PFS). Other secondary endpoints including response rate (RR) according to the RECIST, overall survival (OS) and treatment-related adverse event (TRAE). Total sample size is 48 (one-sided alpha 0.05; power 80%). Results: Total 48 pts were recruited from Oct 2020 to May 2022. Data were frozen on 1 Aug 2022 for analyses. The median follow-up was 11.2m. Seven (14.9%) pts remained on treatment; 1pt was found to ineligible and excluded from the analysis. The median age is 61 (Range 36-83). Aetiology of HCC: HBV 34 (72.3%); HCV 2 (4.3%); alcoholic 8 (17%); Most pts have BCLC stage C (93.6%). All pts have Child’s A liver function. Total 39 (83%) pts receive ICI-based first-line therapy, and 19 (40.4%) pts have prior atezolizumab-bevacizumab (AB) treatment. The median PFS is 4.1m (95% CI 3.3-5.3). Regarding RR, PR and SD occurs in 3 (6.4%) and 36 (76.6%) pts, respectively. The median OS is 9.9m (95% CI 7.3-14.4) and the 1-year survival rate is 45.3%. Amongst the 19 pts receiving prior AB treatment, the median OS is 14.3m (95% CI: 5.5-14.4) with 1-year survival rate of 50.7%. For non-AB regimen, the median OS is 8.9m (95% CI 6.1-NR) with 1-year survival rate of 42.0%. Commonest G3-4 TRAE is thrombocytopenia (6%); hypertension (4%) and ALT elevation (4%).The median dose of cabo is 41.6mg per day (range: 24.3-60.0 mg). Conclusions: Post-ICI use of cabo is associated with a median PFS of 4.1m and median OS of 9.9m. AB-cabo sequence appears to have more favourable outcome than non-AB-cabo sequence. No new safety signals were observed. This clinical trial reports the first prospective post-ICI survival data on TKI. Clinical trial information: NCT04588051 .
Tislelizumab in combination with anlotinib as first-line treatment for unresectable hepatocellular carcinoma: A single-arm, phase II clinical trial.
Authors: Laoguo Shi-xue , Huang Huasheng , Zeng Jie , Jiang Yangfeng , Liu Cuizhen , Mo Ning , Zhu GuangZhi , Ma Fuchao , Peng Tao , Zeng Zhiming , Ma Jie 
Published: January 2023

576 Background: The inability to perform liver resection is an important cause of high mortality in Hepatocellular carcinoma (HCC) patients. Based on the clinical data of anlotinib (a multi-targeted tyrosine kinase inhibitor) and tislelizumab (anti‐PD‐1 antibody) in HCC pts, we therefore evaluated the safety and efficacy of tislelizumab plus anlotinib as first-line therapy for patients with unresectable HCC. Methods: Patients aged 18-75 years, with unresectable HCC, ECOG PS 0-3, BCLC stage A-D, Child-Pugh score A-C, and CNLC stage Ia-IV were enrolled. Patients who met the inclusion criteria received tislelizumab(intravenous drip, 200 mg/d1, Q3W) and anlotinib(oral, 8-12 mg/d1-14, Q3W). The primary endpoint was objective response rate (ORR). The secondary endpoints included disease control rate (DCR),overall survival (OS), progression-free survival (PFS), adverse events (AEs), and serious adverse events (SAEs). Results: Between Sep-2020 until Sep-2022, 37 patients were enrolled, and 25 patients’ clinical data were available to assess clinical efficacy. The median age of the pts was 62 years (ranged 31-72 years), 15 pts (60%) ECOG PS 1, 14 pts (56%) BCLC stage C, 17 pts (68%) Hepatitis B Virus Infection and 13 pts (52%) had received prior local regional therapy. The ORR per mRECIST was 32% (95% CI, 12.3%-51.7%) and DCR was 72% (95% CI, 53.1%-90.9%). The best clinical response was CR in 2 pts (8%), 6 pts (24%) PR and 10 pts (40%) SD. With a median follow-up of 12.7 months, the estimated median PFS was 11.8 months, and the median OS was not reached. The most common AEs during follow-up were AST increased (52%), γ-GT increased (48%), and hypoalbuminemia (48%). Conclusions: Tislelizumab combined with anlotinib showed high antitumor activity and good tolerability in the treatment of unresectable HCC, which may be an effective and safe treatment option.
Phase 2 trial of pembrolizumab (pembro) and bavituximab (bavi) in advanced hepatocellular carcinoma (HCC).
Authors: Hsieh David , Kainthla Radhika , Zhu Hao , Beg Muhammad S. 
Published: January 2023

584 Background: Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and is responsible for more than 500,000 deaths annually. Bavi, a monoclonal antibody designed to inhibit the immunosuppressive effects of phosphatidylserine through interaction with TIM and TAM receptor family members in the tumor microenvironment (TME), is being evaluated in combination with pembro, a monoclonal antibody designed to inhibit Programmed cell death protein 1 (PD-1), in patients with advanced HCC. Methods: This phase 2, open-label, multi-site trial included patients with histologically confirmed locally advanced or metastatic HCC who have not received prior systemic therapy. Patients were treated with pembro (200 mg Q3W) in combination with bavi (3 mg/kg QW) until disease progression. The primary endpoint of the trial is confirmed ORR by RECIST 1.1. A minimax two-stage method to analyze ORR after 15 patients and enroll an additional 13 patient if 3 or more responses observed in first 15 patients (NCT03519997). Results: Three out of 15 evaluable patients responded during Stage 1, allowing for enrollment to continue with a planned 13 additional patients in Stage 2. The study completed enrollment after a total of 28 patients were determined to be evaluable. The confirmed ORR based upon data from 28 patients evaluable for response was 32% (9 confirmed, partial responses). The disease control rate was 61% (9 partial responses, 8 stable disease). The safety profile of pembro plus bavi was consistent with the established profiles of individual drugs and updated adverse events will be reported at the time of presentation along with correlative studies. Conclusions: The combination of bavi and pembro appears to be well tolerated in this patient population and has a toxicity profile comparable to monotherapy immune checkpoint inhibitor. Preliminary analyses suggests that bavi and pembro may have promising anti-tumor activity in advanced HCC. Clinical trial information: NCT03519997 .
A glimpse into the future of cholangiocarcinoma: Predicting the future incidence based on the current epidemiological data.
Authors: Tella Sri Harsha , Wieczorek Mikolaj , Hodge David , Mahipal Amit 
Published: January 2023

616 Background: Cholangiocarcinoma (CCA) is an aggressive, heterogenous group of neoplasms that arise from the epithelial lining of bile ducts that have dismal poor prognosis. A recent epidemiological study in the United States demonstrated a steady increase in the incidence of cholangiocarcinoma from 2001 to 2017 with a predominant increase in the intrahepatic sub-type (iCCA). We sought to evaluate the future incidence of cholangiocarcinoma stratified based on the subtype, age, sex, and race, that could possibly help plan prevention, control, and treatment strategies for this cancer. Methods: We obtained histologically confirmed cases of cholangiocarcinoma (ICD-0-3 Site: C220, C21, and C240) from National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) 18 registries between 2000 to 2017 and predicted the incidence between the years 2018-2029. We applied age-period-cohort models to estimate future cholangiocarcinoma incidence rates (per 100, 000) and the estimated disease burden by multiplying incidence forecasts by corresponding US Census population projections. Results: A total of 12,737 and 8,395 patients with iCCA and extra-hepatic cholangiocarcinoma (eCCA) were included in the final analysis. The median age of iCCA cohort was 64 (range: 20-79) years and 46.4% were females whereas in eCCA the median age was 66 (range: 20-79) years and 43.8% were females. The overall observed age-adjusted incidence of iCCA between 2000-2017 was 1.07, which is predicted to increase to 2.13 by 2029 (99% increase) with a predominant increase in incidence rate observed in the age groups 70-79 and White males and females. Interestingly, incidence rate remained stable in Black and Asian males and in Asian females. Similarly, as compared to 2001-2017, the incidence of eCCA is projected to increase from 0.74 to 1.01 by 2029 (36.5% increase) with predominant increase noted in Black and Hispanic cohorts. In contrast, we noticed a relatively stable and decreasing incidence rate in White and Asian females, respectively. Conclusions: We predict an overall increased incidence of both iCCA and eCCA over the next decade especially in certain subgroups warranting the urgent need for preventive strategies. Further epidemiological studies are needed to determine the etiological factors contributing to predicted increase in incidence rate.
Quality-of-life outcomes after total neoadjuvant short course radiotherapy, chemo-immunotherapy, and total mesorectal excision for locally advanced rectal cancer.
Authors: Shamseddine Ali , Chehade Laudy , Kattan Joseph Gergi , Temraz Sally Naji , Amarin Rula , Awabdeh Tala , Charafeddine Maya , Al Darazi Monita , Turfa Rim 
Published: January 2023

63 Background: A growing body of evidence supports total neoadjuvant therapy (TNT) for locally advanced rectal cancer (LARC), however the optimal regimen is yet to be determined and little is known on the quality-of-life (QOL) implications of these therapies. We report QOL data from the Averectal study, which assessed the efficacy and safety of neoadjuvant short course radiotherapy (SCR) plus chemo-immunotherapy for patients with LARC. Methods: Between July 2018 and October 2020, patients enrolled in the Averectal study were invited to fill the Functional Assessment of Cancer Therapy for colorectal cancer (FACT-C) throughout their treatment. We analyzed results at baseline (T0), at completion of SCR and chemo-immunotherapy (T1), and at last-follow up after total mesorectal excision (TME) (T2). Paired sample t-test was used to compare mean scores for individual patients. Results: 39 patients completed the FACT-C form at the specified points. Median follow-up duration was 25.7 months. Median age was 58 years (range 31-74 years), 25 (64.1%) were males, 1 (3.1%) had stage II disease and the rest (96.9%) had stage III. All patients received SCR then 6 cycles of mFOLFOX-6 plus avelumab followed by TME. The mean score differences of the FACT-C subscales at different time-points are summarized. At the end of TNT, the social (SWB), emotional (EWB), functional well-being (FWB) and colorectal cancer subscale (CCS) scores improved compared to baseline (not significant) but physical well-being score (PWB) worsened (21.05 vs 22.94 p=0.025). After TME, all scores except EWB and FWB improved compared to T1, and all scores improved compared to baseline. The CCS, which assesses colorectal cancer specific concerns, significantly improved between T0 and T2 (19 vs 21.06, p=0.003). Overall, trial outcome index (TOI), reflecting functional status, improved after TME compared to baseline. Conclusions: Adopting neoadjuvant chemo-immuno-radiotherapy followed by TME for LARC does not result in QOL deterioration compared to baseline, and can improve colorectal cancer specific concerns. Clinical trial information: NCT03503630 . [Table: see text]
Clinical and radiological response to locoregional and systemic treatments in well-differentiated gastroenteropancreatic neuroendocrine tumors with liver metastases treated at a reference center in Mexico.
Authors: Arce Sandoval Cesar , Meneses Medina Mónica Isabel , Cisneros Cordero Miriam Heidi , Hernandez-Felix Jorge Humberto , Rosas Camargo Vanessa , Torres Valdiviezo Lucero Itzel , Ramirez Rixci , Gabutti Thomas Jesus Alejandro , Huitzil Melendez Fidel David David 
Published: January 2023

644 Background: liver metastases (LM) from well-differentiated gastroenteropancreatic neuroendocrine tumors (wd-GEP-NET) can develop in 28-77% of patients (pts) in their lifetime. Multiple treatments can provide radiological and symptomatic response. Our aim was to evaluate responses to locoregional (LRT) and systemic (SYST) treatments in wd-GEP-NET with LM. Methods: we included consecutive records of pts with confirmed histological diagnosis of wd-GEP-NET and radiological LM, treated at our institution between 2008-2019. Relevant variables were retrospectively extracted from electronic records. Radiological response was assessed with RECIST 1.1 by radiological independent review. Results: 55 pts, 45.5% male. Median age at LM diagnosis 49 years (IQR 41-63). Primary tumor sites: 49% pancreatic, 27.3% small intestine, 11% unknown, 12.7% others. WHO 2019 grade 1, 2 and 3 in 52.7, 41.8 and 1.8%, respectively. Twentynine tumors (52.7%) were functional, with carcinoid syndrome in n20. At LM diagnosis, 91% of pts had symptomatic disease: hormonal n8, local n4, systemic n4, hormonal + local n4, local + systemic n22, hormonal + systemic n5, hormonal + local + systemic n5. LM tumoral burden was <10% in 22%, 11-50% in 43.6, > 50% in 30.9% of pts. 49.1% of pts had extra hepatic metastatic disease. LRT to LM was administered to 32 pts: TAE/TACE n26, ablation n8. SYST to 22 pts: somatostatin analog n15, Lutetium-177 n4, chemotherapy n2, everolimus n1. 1 pt did not receive treatment. Response to treatments is shown. In the LRT group, -- pts developed complications: n16 postembolization syndrome, n2 infections, n3 liver failure, n7 others. There was 1-procedure-related death. Conclusions: Patients treated with LRT at our institution achieved similar efficacy and safety results compared to those reported by previous studies.[Table: see text]
Evaluating surgical treatment options for small nonfunctional pancreatic neuroendocrine tumors in the NCDB.
Authors: Sugawara Toshitaka , Rodriguez Franco Salvador , Kirsh Michael , Colborn Kathryn , Ishida Jun , Grandi Samuele , Al-Musawi Mohammed , Gleisner Ana , Schulick Richard D. , Del Chiaro Marco 
Published: January 2023

645 Background: The role of surgery for small (≤2 cm), nonfunctional pancreatic neuroendocrine tumors (NF-PNETs) remains controversial due to the wide range of tumor aggressiveness. Consensus guidelines of the US, Europe, and Japan offer different recommendations for treatment of small NF-PNETs. The objective of this study is to evaluate the survival benefit of surgical resection for small NF-PNETs. Methods: Patients with NF-PNETs were identified in the National Cancer Database from 2004 to 2018. Small NF-PNETs were divided into two groups: group 1a (tumor ≤1 cm) and group 1b (tumor 1.1 – 2.0 cm). Cox regression models were used to compare the overall survival between resected and unresected small NF-PNETs patients. Interactions between preoperative factors and surgery were estimated using subgroup analyses. Results: We identified 1,278 patients in group 1a and 3,363 patients in group 1b. After adjusting for preoperative factors, surgery was associated with longer survival for patients in group 1b (HR, 0.58; 95% CI, 0.42–0.80; P <0.001), but not for patients in group 1a (HR, 0.68; 95% CI, 0.41–1.11; P = 0.122). Interaction analysis found that age younger than 65 years, fewer comorbidities, treatment at academic institutions, distal pancreatic tumors, and clinical lymph node metastasis were factors associated with longer survival in group 1b by surgery. Conclusions: Findings from this large study support surgical resection for some patients with NF-PNETs (1.1 – 2.0 cm). This, of course, must be taken in context with the patient’s clinical situation. Based on data available for analysis in this study, resection for subcentimeter NF-PNETs does not appear to be of general benefit, but should also be investigated in the context of Ki-67 index.[Table: see text]
Proteomic profiling of antibody-drug conjugate (ADC) biomarkers in pancreatic cancer.
Authors: Thyparambil Sheeno P. , Liao Wei-Li , Heaton Robert , Strasbaugh Amanda , Melkie Marya Abebe , Ling Xuefeng 
Published: January 2023

671 Background: Pancreatic cancer (PaC) is a highly fatal disease with a 5-year survival rate of 5-10%. Effective screening is not available, and most patients (50-55%) present with metastatic (50%-55%) disease at diagnosis. For patients with advanced PaC, the standard chemotherapy combinations include FOLFIRINOX and/or gemcitabine/nab-paclitaxel which has results in a overall survival of 7-11 months. The lack of effective therapies underscores the importance of exploring other agents. We propose that quantitating therapy-associated protein biomarkers including markers of antibody-drug conjugates (ADC) can improve treatment personalization for PaC. Methods: FFPE tumor tissues from 185 clinical PaC patients were microdissected and solubilized for mass spectrometry-based targeted proteomic analysis. We quantified biomarkers for ADCs simultaneously from 2-3 section of FFPE. These biomarkers include antibody targets such as EGFR, HER2, HER3, FRalpha, and Trop2 and payload biomarkers of sensitivity (TOPO1) and resistance (TUBB3). The multiplexed assay also quantified additional 65 clinically relevant protein biomarkers for chemotherapy, immunotherapy and targeted therapy. Results: Expression of EGFR was observed in majority of samples (88%) while only overexpressed ( > 1000 amol/µg) in 3% of samples. HER2 was expressed in half of patients (52%) and overexpressed ( > 750 amol/µg) in 5% of cases while the rest of HER2 protein expression ranged from 300 -750 amol/µg which corresponds to low Her2 expression. Trop2 was expressed in majority of patients (91%) with a 25x distribution between lowest and highest expressor. Other ADC biomarkers include HER3(55%, 5x), Axl (24%, 12x), Mesothelin (65%, 58x), Folate receptor alpha (10%, 17x). Expression of TUBB3 (77%, 8x) and TOPO1 (92%, 8x) in antibody target-positive subset may suggest resistance or response for several known payloads, such as taxanes and irinotecan/deruxtecan/govitecan, respectively. Conclusions: There is currently no approved ADC for pancreatic cancer, but several ADC clinical trials are underway. Quantitative proteomics identified antibody targets as well as markers of resistance or response to payloads for a variety of approved and investigational ADC therapies, which could aid in patient stratification in ADC clinical trials.
Prognostic factors of multidisciplinary treatment for borderline resectable and locally advanced pancreatic adenocarcinoma: Results of a dual-center study.
Authors: Kimura Nana , Igarashi Takamichi , Yamada Suguru , Murotani Kenta , Yoshioka Isaku , Takami Hideki , Shibuya Kazuto , Hayashi Masamichi , Tanaka Haruyoshi , Hirano Katsuhisa , Watanabe Toru , Tanaka Nobutake , Baba Hayato , Tohmatsu Yuuko , Sakai Ayano , Fukasawa Mina , Matsui Koshi , Okumura Tomoyuki , Kodera Yasuhiro , Fujii Tsutomu 
Published: January 2023

680 Background: Multidisciplinary treatment of borderline resectable (BR)/unresectable locally advanced (UR-LA) pancreatic adenocarcinoma (PDAC) has not yet been established. The purpose of this study is to explore factors that improve prognosis in radical surgery after multidisciplinary treatment for pancreatic cancer. Methods: We evaluated the following prognostic factors in 240 PDAC patients who underwent radical resection after multidisciplinary treatment. Patients were classified into 3 groups according to NCCN guidelines (BR PDAC invading the portal vein (BR-PV), BR pancreatic cancer in contact with the major arteries such as the hepatic artery, celiac axis and superior mesenteric artery (BR-A), and UR-LA), and prognostic factors were investigated. Patients with BR PDAC were treated with chemotherapy followed by surgery, while radiation therapy was added preoperatively in most cases with arterial invasion. All patients with UR-LA underwent surgery after nab-paclitaxel plus gemcitabine (GnP) followed by chemoradiotherapy (CRT) with S-1. Results: BR-PV/BR-A/UR-LA patients were 88/111/41, respectively. Prognosis was significantly better in the NAT group than in the upfront surgery group for both BR-PV/A (P=0.004/<0.001). In univariate analysis of overall survival (OS) in 36 patients with BR-PV who underwent resection after NAT, the following factors were significantly favorable prognostic factors; tumor marker (TM) normalization (P=0.028), preoperative Glasgow prognostic score=0 (P=0.025), and preoperative prognostic nutritional index (PNI)>42.5 (P=0.022). In univariate analysis in 39 patients with BR-A, the following factors were significantly favorable prognostic factors; TM normalization (P=0.033), preoperative PNI>42.5 (P=0.013), intraoperative blood loss>830 ml (P=0.013). Multivariate analysis revealed that high preoperative PNI was an independent prognostic factor (hazard ratio 0.15 [0.02-0.85]; P=0.014) in BR-A patients. In patients with UR-LA who underwent radical resection after GnP and subsequent CRT, median duration of NAT was 8.8 months, and R0 resection was achieved in 36 patients (88%). 3-year OS was 77.4%, and 5-year OS 58.6%. Multivariate analysis revealed that CA19-9 normalization (hazard ratio 0.23 [0.02-0.88]; P=0.032) and PNI≥41.7 (HR 0.05 [0.01-0.62]; P=0.021) were independent prognostic factors. Conclusions: In both BR/UR-LA pancreatic cancer, normalization of TM and maintenance of good nutritional status during NAT until surgery may contribute to prolonged prognosis.