bluuebunny/crossref_metadata_2025 huggingface dataset:
Value-based preoperative assessment in a large academic hospital
Authors: Cecconi Maurizio , Goretti Giulia , Pradella Andrea , Meroni Patrizia , Pisarra Martina , Torzilli Guido , Montorsi Marco , Spinelli Antonino , Zerbi Alessandro , Castoro Carlo , Casale Paolo , Civilini Efrem , Quagliuolo Vittorio , Klinger Marco , Spriano Giuseppe , Vitobello Domenico , Maradei Leonardo , Reimers Bernhard , Piccioni Federico , Martucci Maria Rosaria , Stomeo Niccolò , Vanni Elena , Babbini Marco , Monzani Roberta , Capogreco Maria Rosaria , Lagioia Michele , Greco Massimiliano
Published: July 2024

Background

Value-based healthcare (VBHC) is an approach that focuses on delivering the highest possible value for patients while driving cost efficiency in health services. It emphasizes improving patient outcomes and experiences while optimizing the use of resources, shifting the healthcare system’s focus from the volume of services to the value delivered. Our study assessed the effectiveness of implementing a VBHC-principled, tailored preoperative evaluation in enhancing patient care and outcomes, as well as reducing healthcare costs.

Methods

We employed a quality improvement, before-and-after approach to assessing the effects of implementing VBHC strategies on the restructuring of the preoperative evaluation clinics at Humanitas Research Hospital. The intervention introduced a VBHC-tailored risk matrix during the postintervention phase (year 2021), and the results were compared with those of the preintervention phase (2019). The primary study outcome was the difference in the number of preoperative tests and visits at baseline and after the VBHC approach. Secondary outcomes were patient outcomes and costs.

Results

A total of 9722 patients were included: 5242 during 2019 (baseline) and 4,480 during 2021 (VBHC approach). The median age of the population was 63 (IQR 51–72), 23% of patients were classified as ASA 3 and 4, and 26.8% (2,955 cases) were day surgery cases. We found a considerable decrease in the number of preoperative tests ordered for each patient [6.2 (2.5) vs 5.3 (2.6) tests, p < 0.001]. The number of preoperative chest X-ray, electrocardiogram, and cardiac exams decreased significantly with VBHC. The length of the preoperative evaluation was significantly shorter with VBHC [373 (136) vs 290 (157) min, p < 0.001]. Cost analysis demonstrated a significant reduction in costs, while there was no difference in clinical outcomes.

Conclusions

We demonstrated the feasibility, safety, and cost-effectiveness of a tailored approach for preoperative evaluation. The implementation of VBHC enhanced value, as evidenced by decreased patient time in preoperative evaluation and by a reduction in unnecessary preoperative tests.
Neoadjuvant cadonilimab (PD-1/CTLA-4 bispecific antibody) plus FLOT chemotherapy in locally advanced gastric/gastroesophageal junction cancer (GC/GEJC): A prospective, multi-center, phase II study.
Authors: Jiao Zuoyi , Zhou Huinian , Yu Zyuaun , Long Bo , Huang Zeping , Zhao Da , Wei Dengwen , Zhao Xiaonin , Jiang Zebin , Yang Xiaojun
Published: July 2024

e16108

Background: FLOT remains the preferred neoadjuvant treatment (NAT) for locally advanced GC/GEJC, with evidence suggesting enhanced efficacy when plus PD-1 inhibitors. Cadonilimab, a bispecific antibody targeting PD-1 and CTLA-4, also exhibited survival benefits when combined with chemotherapy as first-line treatment for GC/GEJC. This study aimed to assess the efficacy and safety of Cadonilimab and FLOT as NAT in locally advanced GC/GEJC. Methods: Pathologically confirmed treatment-naïve patients (pts), aged 18-75, with radiologically evaluable primary GC/GEJC at stage cT3/4, ECOG PS 0-1, were enrolled. The study used simon-2 stage design with a total sample size of 38 pts and would be considered effective if more than 4 pts achieved pCR. Pts received surgery after completing NAT with Cadonilimab (10mg/kg, iv, Q3W) and FLOT (50mg/m² docetaxel, 85mg/m² oxaliplatin, 2600mg/m² 5-FU, and 200mg/m² leucovorin, iv). The primary endpoints were pCR and MPR rate. Secondary endpoints included ORR, DCR, R0 resection rate and safety (CTCAE 5.0). Results: In this phase II trial, initially enrolled 29 pts in stage I, with an additional 9 pts in stage II. Of the 34-evaluable pts, 30 pts underwent surgery. The median age was 57 years (range, 38-74), with 88.2% male and 64.7% diagnosed as stage cT4. According to RECIST1.1 criteria, 5 pts (14.7%) achieved CR, and 21pts (61.8%) achieved PR, with an ORR of 76.5% and DCR of 100.0%. According to Becker criteria for Tumor Regression Grade: 6 pts (20.0%) achieved TRG1a, 9 pts (30.0%) reached TRG1b, with a pCR rate of 20.0% and MPR rate of 50.0%. Pts with diffused and poorly differentiated tumors had higher rates of pCR and MPR (36.4%, 81.8%) than the overall population. A notable tumor downstaging was observed: 86.7% in T stage, 70.0% in N stage, and 70.0 in overall TNM stage. During the NAT phase, all 34 pts experienced TRAEs. Mild to moderate TRAEs (grade 1-2) were observed in 73.5% (25 patients), while 26.5% (9 patients) experienced grade 3 TRAEs. There were no reports of grade 4-5 or severe TRAEs. The most common TRAEs were nausea (100.0%), alopecia (97.1%), vomiting (85.3%), fatigue (85.3%), electrolyte disturbance (79.4%) and rash (73.5%). In post-surgery, all 30 pts achieved R0 resection. Surgical complications were relatively minor, predominantly fever (46.7%), ascites (30.0%) and pneumonia (23.3%). The survival benefit will be reported after the follow-up completed. Conclusions: Neoadjuvant Cadonilimab plus FLOT chemotherapy exhibit encouraging anti-tumor effectiveness and manageable toxicities, particularly in pts with diffused Lauren`s classification and poorly differentiation. This immunochemotherapy regimen might provide a promising alternative NAT option for locally advanced GC/GEJC. Clinical trial information: ChiCTR2200066893.
Patients with metastatic cholangiocarcinoma in Italy and their healthcare resource consumptions and related costs.
Authors: Esposito Immacolata , Ronconi Giulia , Dondi Letizia , Calabria Silvia , Piccinni Carlo , Dondi Leonardo , Dell'anno Irene , Addesi Alice , Martini Nello
Published: July 2024

e16139

Background: Patients with cholangiocarcinoma (CCA) are often diagnosed at late-stage disease. Few or any therapeutic options are possible for older patients with metastases (mCCA) and comorbidities. This analysis aimed to identify and characterize newly mCCA diagnosed patients in Italy in terms of clinical features, healthcare resource consumptions and related costs charged to the Italian National Health Service (SSN). Methods: From the Fondazione ReS (Ricerca e Salute) database (~5 million inhabitants/year), among adults with primary/secondary in-hospital diagnosis of CCA in 2018 and analysable look-back period until 2013, patients newly diagnosed with lymph nodes/distant metastases (index date) were selected. They were characterized by age, sex, and comorbidities (cardiometabolic, respiratory and cerebrovascular disorders, depression, chronic kidney disease and inflammatory bowel diseases). Rate of antineoplastic treatment dispensations and hepatic metastasectomy, overall and progression-free survivals - through Kaplan-Meier curves - among patients treated (vs untreated), and healthcare costs charged to the SSN were assessed during 2 years following index date. Results: In 2018, 176 newly mCCA diagnosed patients (incidence: 4.4x100,000 adult inhabitants; 31% of CCA patients) were identified. Males were 52.3%. Mean age was 72±10 years, and 65% of patients had ≥2 comorbidities. During 1 year following index date, 45.5% of newly mCCA diagnosed patients underwent antineoplastic treatment and/or surgery (mean age was 69±9 years), of whom, 61% were males, 67% had ≥2 comorbidities. During 2 years following index date: 34 patients were lost from 1st to 2nd year; 77% of treated patients died (vs 93.8% untreated; p < 0.01); 87.5% of treated patients relapsed, on average after 6.3 months following index date. On average, during 1st and 2nd follow-up year, respectively: each mCCA patient weighed on the SSN € 12,699 and € 8,298; hospitalizations accounted 87% and 78% of the respective total expenditure. From 1st to 2nd follow-up year, respectively, the expenditure for hospitalizations and pharmaceuticals decreased from € 11,017 to € 6,498 and from € 700 to € 590, while costs for local outpatient services increased from € 982 to € 1,210. Conclusions: This study suggests that newly mCCA diagnosed patients strongly impact on the SSN, and that antineoplastic treatments and/or surgery, if applicable, can reduce mortality with substantial survival benefit.
Update results of anlotinib plus TQB2450 (PD-L1 blockade) combined with nab-paclitaxel and cisplatin as first-line treatment for advanced biliary tract cancer: A single-arm, open-label phase II clinical trial.
Authors: Guo Wen-Zhi , Li Lu-Hao , Qiao Shishi , Li Ren-Feng , Zhang Weijie , He Wei , Su Chang , Pan Jie , Jin Shui-Ling , Zong Hong
Published: July 2024

e16144

Background: Efficacy and prognosis of chemotherapy in first-line setting for patients with advanced biliary tract cancer (BTC) was dismal currently. Recently, PD-1/PD-L1 blockades combined with dual chemotherapy in first-line setting exhibited superior efficacy for patients with BTC. Nevertheless, it's important to highlight that both the TOPAZ-1 and KEYNOTE-966 trials had reported a median OS of less than 13 months. This underscored the necessity for further advancements to meet the demands of clinical practice. Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, demonstrated promising therapeutic activity as second-line therapy for patients with BTC. Therefore, this study was designed to explore the efficacy and safety of anlotinib plus TQB2450 (PD-L1 blockade) combined with nab-paclitaxel and cisplatin as first-line therapy in advanced BTC. Preliminary results were presented at the 2024 ASCO-GI Symposium (Abs 498), the consecutively updated results were presented in this report. Methods: Patients with previously untreated metastatic or locally advanced BTC (ICC, ECC, GBC) were recruited and treated with anlotinib (10mg, po, d1~14, q3w) and TQB2450 (1200mg, iv, d1, q3w) plus nab-paclitaxel (200mg/m2, iv, d1, q3w) and cisplatin (60mg/m2, iv, d1, q3w) until disease progression or unacceptable toxicity. The predefined sample size was 20. Primary endpoint was ORR and secondary endpoints included safety, DCR, PFS, OS and biomarker explore. Results: From April 2023 to Oct 2023, a total of 20 patients were enrolled. At the data cut-off date (Jan, 2024), the best overall response indicated that there were 12 PR (60.0%), 6 SD (30.0%) and 2 PD (10.0%). Therefore, the preliminary ORR was 60.0% (95%CI: 36.1%-80.9%), DCR was 90.0% (95%CI: 68.3%-98.8%). At the data cut-off date, the preliminary prognostic result exhibited that the median PFS of the 20 pts was 8.31 months (95%CI: NA~NA). Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-emergent adverse events among the 20 patients with the incidence > 30% were leukopenia (80%), peripheral sensory neuropathy (45%) and fever (35%). Common grade ≥3 treatment-emergent adverse events were leukopenia (30%), fever (5%), decreased platelet count (5%), malaise (5%), nausea (5%), stomachache (5%), oral mucositis (5%), vomit (5%), rash (5%) and hypotension (5%). Conclusions: Preliminary results suggested that anlotinib plus TQB2450 combined with nab-paclitaxel and cisplatin as first-line therapy in advanced BTC exhibited encouraging efficacy and manageable adverse events. The conclusion should be validated in more patients consecutively. Clinical trial information: NCT05812430 .
Cadonilimab in combined with gemcitabine and cisplatin in advanced biliary tract cancer (BicureX): A phase II, single-arm clinical trial.
Authors: Ma Ji , Wang Tao , Chen Yidi , Yang Yi , Qiu Yiwen , Shen Shu , Yi Cheng , Wang Wentao
Published: July 2024

e16158

Background: PD-1 or PD-L1 inhibitors plus chemotherapy as the first-line treatment has been proven to be effective in improving the prognosis of advanced biliary tract cancer (BTC) patients. However, there is still considerable demand for further improvement of BTC patients’ prognosis. This trial aims to evaluate the efficacy and safety of Cadonilimab (PD-1/CTLA-4, a bi-specific antibody) plus gemcitabine and cisplatin for patients with advanced BTC in first -line treatment. Methods: In this phase II, single-arm trial, we will enroll 65 patients with previously untreated, unresectable, locally advanced or metastatic BTC, including intrahepatic or extrahepatic cholangiocarcinoma (ICC/ECC) and gallbladder carcinoma (GBC). Participants received Cadonilimab (10 mg/kg, days 1, every three weeks) plus gemcitabine (1000 mg/m2, days 1, 8, Q3W), and cisplatin (25 mg/m2, days 1, 8, Q3W) for up to eight cycles, followed by Cadonilimab (10 mg/kg, days 1, Q3W) until disease progression or unacceptable toxicity. Treatment response was evaluated with image-based assessment according to response evaluation criteria insolid tumors (RECIST) version 1.1. by two experienced experts and further explored multiple methods, such as 3D visualisation and Spectral computed tomography Scan. The primary endpoint was the objective response rate (ORR); the secondary endpoints are disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory endpoints included associations between response, molecular characteristics, and the immune microenvironment. Results: Between June 30, and January 31, 2024, a total of 30 patients have undergone at least one imaging evaluation. 66.7% of these patients were diagnosed with ICC, 23.3% with GBC, and 10% with ECC. The mean age was 58.4 years, and 60% of the patients were male. 24 (80%) patients had metastasis. Among them, 1 (3.3%) patient acheived complete response (CR), 15 (50%) patients had partial response (PR) and 8 (26.7%) patients presented with stable disease (SD). The ORR was 53.3% and the DCR was 80%. The most common treatment-related adverse events (TRAEs) of any grade were rash (80%) and anaemia (76.7%). Grade 3 TRAEs were observed in 66.7% of the patients. The most frequent grade 3 TRAEs were anaemia (33.3%), and leukocytopenia (33.3%). No grade 4 or 5 events were observed. All patients were microsatellite stable (MSS), and the median TMB was 2.88 (0-109.44) Muts/Mb. Conclusions: Cadonilimab plus gemcitabine and cisplatin shown a promising efficacy and acceptable safety profile as first-line treatment for advanced BTC patients. Clinical trial information: NCT05978609 .
Efficacy and safety of regorafenib and/or immune checkpoint inhibitors as a second-line therapy for advanced hepatocellular carcinoma: A real-world study from a single center.
Authors: Liu Songtao , Huang Xueying , Chen Jingjing , Wei Qiaoxin , Liu Mei
Published: July 2024

e16165

Background: This study aimed to assess the efficacy and safety of regorafenib and/or immune checkpoint inhibitors (ICIs) as a second-line treatment in patients with pretreated hepatocellular carcinoma (HCC). Methods: Patients diagnosed with advanced HCC who had received regorafenib treatment in our hospital from January 2020 to November 2023 were reviewed. Overall survival (OS) was the primary endpoint. Progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR) and toxicity were the secondary end points. Results: Forty-five patients were included with a median age of 61 (31-83) years. Thirty-two patients (71.1%) were in Barcelona Clinic Liver Cancer (BCLC) stage C. Twenty-three patients (51.1%) had extrahepatic metastasis. ICIs were applied to 30 patients (66.7%) at the use of regorafenib. Local treatments were applied to 17 patients (37.8%). The median OS was 14.5 (11.3, 26.4) months in all patients. Regorafenib plus ICIs had a longer survival than regorafenib alone (20.5 [11.6, NA] vs 11.3 [3.0, 13.9] months, P = 0.019). Local treatment had no obvious effect. The median PFS was 6.8 (4.5, 11.7) months in all patients. The median PFS was 9.7 (4.6, 14.5) months in regorafenib plus ICIs that was longer than regorafenib alone with 3.0 (2.0, 8.0) months. Local treatment only showed a trend of prolongation (11.8 [2.5, 22.6] vs 4.7 [3.5, 9.7] months, P = 0.059). The 1-year OS and PFS were 43.2% and 20.0%, respectively. ORR and DCR was 29.0% and 71.0% according to mRECIST criteria, respectively. The most common any-grade treatment-related adverse events (TRAEs) were rash/itching (41.3%), hand-foot syndrome (19.6%), and anorexia (13.0%). Grade≥3 TRAEs occurred in 8.9% (4/45) of the patients and hypertension (4.4%) had the highest proportion. Conclusions: Regorafenib plus ICIs therapy is an effective promising regimen regardless of first-line treatments in advanced HCC. Combined with local treatment only showed a trend of PFS, further prospective research is needed.
Efficacy and safety of regorafenib combined with PD-1 inhibitors in patients with advanced hepatocellular beyond atezolizumab plus bevacizumab: A retrospective analysis of real-world evidence.
Authors: Zhang Xinfeng , Cheng Jiamin , Chen Bowen , Zhang Tianlan , Li Yinyin , Zhang Linzhi , Dong Jinghui , Lu Yinying
Published: July 2024

e16172

Background: In patients with advanced hepatocellular carcinoma (HCC) progressing after atezolizumab and bevacizumab, the optimal therapy scheme is debatable and the efficacy of regorafenib combined with PD-1 inhibitors is still unclear. Methods: In this retrospective study, advanced HCC patients who received regorafenib combined with PD-1 inhibitors progressing after atezolizumab plus bevacizumab were consecutively enrolled from February 2022 to January 2024. Main efficacy endpoint was overall survival (OS), following progression free survival (PFS), evaluated in accordance with RECIST v1.1. Adverse events (AEs) were recorded according to CTCAE v5.0. Results: A total of 11 eligible patients were enrolled, with 8 in Child-Pugh A and 3 in Child-Pugh B7. All patients had hepatitis B infection by with tumor embolus. All patients were classified as Barcelona Clinic Liver Cancer stage C. The AFP level is above 400ng/ml in all patients. At data cut-off at February 2024, the median OS was 16.9 months and the median PFS was 3.7 months. The 3-month and 6-month PFS rates were 70% and 35% , respectively. The 12-month OS rate was 71.4%. Grade≥3 TRAEs occurred in 9.1% (1/11) of the patients. Conclusions: Though application of regorafenib combined with PD-1 inhibitors progressing after atezolizumab plus bevacizumab present safe and effective in our cohort, these data need to be confirmed in prospective comparative studies. [Table: see text]
The activity and safety of icaritin for patients with unresectable HCC: A real world, retrospective study.
Authors: Shao Guoliang , Jiang Wentao , Zheng Xin , Xiang Huiling , Wang Song , Zhou Xu , Lin Nan , Yu Zheng-Ping , Dong Ke , Cao Mingrong , Xie Qinfen , Zeng Hui , Zhang Zhewei , Luo Jun
Published: July 2024

e16181

Background: Primary liver cancer is a major health burden globally, ranking sixth in incidence and third in mortality among all cancers[1]. Over the past 5 years, immune checkpoint inhibitors (ICIs) and multi-targeted tyrosine-kinase inhibitors have emerged as new treatment options for advanced hepatocellular carcinoma[2–4]. Nevertheless, only a small subset of patients with hepatocellular carcinoma derive a response to ICI monotherapy. Icaritin, a target tumor micro-environment(TME) modulating compound, which interacts with MyD88/IkB kinase-a (IKK)[5], inhibiting the TNF-a-induced IKK and nuclear factor-κB (NF-kB) signaling pathways and blocking PD-L1 expression in HBV-related HCC[6-9] and has been approved in China for the treatment of first-line advanced HCC. Icaritin phase III study previously reported at 2021 ASCO, we therefore investigated the efficacy of icaritin in patients with unresectable stage IIA-IIIB (CNLC stage) HCC in a real-world setting. Methods: This multi-center, retrospective study, conducted between May 2022 and Nov 2023. We retrospectively collected medical records of patients (pts) with unresectable IIA-IIIB (CNLC stage) HCC who received icaritin monotherapy (mono-group) or icaritin combined with PD-1/L1 and/or anti-VEGF therapy (combination group) as first line therapy. The primary endpoints were progression free survival (PFS); Secondary endpoints included overall survival (OS) rate, objective response rate (ORR) by RECIST v1.1, and safety. Results: Patients characteristics: 49 pts were eligible for inclusion with median age of 60.7 years old (range 18.0-89.0), 91.8% were ECOG PS 0-1, 86.5% had HBV infection, 79.6% were stage III and 48.9% were AFP>400 ng/ml. 33 pts administrated with combination therapy, other 16 pts’ regimen was icaritin monotherapy. Efficacy: As of the data cutoff for the preliminary analysis of progression free survival (Nov 30, 2023), the median follow-up was 11.17 months (95%CI 6.74–12.12). The ORR for the combination group was 6.06%, and 12.50% for the mono-group, the mPFS was 8.94(95%CI 6.90~9.76) and 5.52 (2.92~NE) for each group. The mOS was not reached for both group, the 6 and 12-months OS rates were 91.00% and 73.67% respectively. Safety: For the safety information, most of TRAEs were grade 1 or 2. No serious AEs were observed. Conclusions: This real-world retrospective study revealed that icaritin monotherapy and icaritin-based combination therapy are promising therapeutic options for unresectable HCC in China. Clinical trial information: ChiCTR2300074565.
Hepatic artery infusion chemotherapy (HAIC) plus sintilimab and bevacizumab biosimilar (IBI305) in initial unresectable hepatocellular carcinoma (HCC): A retrospective study.
Authors: Zhang Xihao , Liu Yang , Fu Linlin , Liu Yayue , Qi Qi , Li Rentao , Cui Yunlong , Lu Wei , Li Huikai
Published: July 2024

e16185

Background: Combining sintilimab with IBI305 has shown significant survival benefits over sorafenib in first-line HCC treatment. Our prior study has indicated improved outcomes with sintilimab and bevacizumab biosimilar (IBI305) in combination with HAIC for HCC (Clinical trial: NCT05029973). This study aims to evaluate combining HAIC with sintilimab and IBI305 for initial unresectable HCC in real word. Methods: Eligible patients (pts) had histologically or cytologically diagnosed or clinically confirmed HCC, with China liver cancer staging (CNLC) stage Ib-IIIb, no prior systemic treatment, Child-Pugh A or B, and ECOG 0 or 1. Patients were administered FOLOFOX-HAIC, combined with intravenous Sintilimab (200 mg, Q3W) and intravenous IBI305 (7.5 mg/kg, Q3W). Primary endpoints included objective response rate (ORR) and disease control rate (DCR) per modified Response Evaluation Criteria in Solid Tumors (mRECIST). Secondary endpoints included surgical conversion rate, R0 resection rate, and pathological complete response (pCR) rate. Results: Data were collected from 106 patients (from Apr, 2021 to Jul, 2023), median age 61, with the majority being male (91, 85.9%), ECOG 0 (106, 100%), and classified as Child-Pugh A (82, 77.4%). CNLC staging: Ib (19), IIa (2), IIb (20), IIIa (42), IIIb (23). HBV infection: 84 (79.3%), HCV: 3 (2.8%). AFP levels were > 400ng/ml in 53 patients (50.0%), with tumor diameters > 10 cm in 47 patients (44.3%). Single tumors were noted in 35 patients (33.0%), vascular invasion in 60 patients (56.6%), and extrahepatic metastasis in 26 patients (24.5%). Among the 106 patients evaluable for response, ORR was 39.6% with 42 patients demonstrating partial responses (PR); DCR was 96.2% (102/106), comprising 42 PR, 60 stable disease (SD). The surgical conversion rate was 40.56% (43/106), achieving R0 resection in all 43 patients and complete pathological response (pCR) in 9/43(20.9%) patients and major pathological response (MPR) in 12/43 (27.9%). The 1-year progression-free survival (PFS) and overall survival (OS) rates were 54.5% and 74%, respectively. The 2-year PFS and OS rates were 41.4% and 58.6%, respectively. No new safety signals were observed, and no treatment-related adverse events (TRAEs) led to death. Conclusions: Combining HAIC with Sintilimab and IBI305 as conversion therapy for unresectable HCC shows promising benefits with manageable safety.
Body mass index (BMI) as a prelude to hepatocellular carcinoma (HCC) and metabolic dysfunction–associated steatohepatitis (MASH) risk factors in patients with no identified risk factor for developing hepatocellular carcinoma (HCC).
Authors: Al Mahmasani Layal , Capanu Marinela , Srivastava Amitabh , Chou Joanne F. , Shia Jinru , El Dika Imane H. , Yaqubie Amin , Harding James J. , O'Reilly Eileen M. , Abou-Alfa Ghassan K.
Published: July 2024

e16193

Background: Common risk factors for hepatocellular carcinoma (HCC) include viral hepatitis (hepatitis B and hepatitis C), alcoholic liver disease, and metabolic dysfunction-associated steatohepatitis (MASH). Non-risk factored HCC has been suggested where patients who do not have common risk factors develop HCC (Journal of Clinical Oncology Volume 35, Number 15_suppl, May 2017). This is described more commonly among young, females more than males. Is this a misdiagnosis or a truly non-factored risk? Methods: Patients diagnosed with histology confirmed HCC between years 2014 and 2017 with none of the known HCC risk factors, were assessed part of our previous effort add to more recent gathered data at Memorial Sloan Kettering (MSK). In an institutional IRB approved retrospective study, demographic and treatment data in addition to DNA sequencing were compiled and evaluated. Detailed clinical and genomic information was abstracted from the medical record. Pathology data was reviewed (AS). Results: A total of 428 patients diagnosed with HCC were identified, of whom 18 (4.2%) patients had no identifiable HCC risk factors. Fourteen patients were females (78%), and four were males (22%). Median age at diagnosis was 59 years (range 18-77 years). All 18 patients did not meet any of the clinical and/or radiologic alleged criteria for a diagnosis of MASH. The average body mass index (BMI) was 27.9 kg/m2 (16.7-54.4). Six patients (33%) had BMI greater than 30 kg/m2, and five (28%) patients had BMI ranging from 25 to 29.9 kg/m2. Three patients had diabetes mellitus. With the lack of non-tumorous liver cancer surrounding tissue, only three patients had mild steatosis documented on pathology. At the molecular level, few somatic mutations were detected including TERT and CTNNB1 in 37% of cases. No germline mutations were identified in 4 tested patients. Conclusions: Among 18 patients diagnosed with HCC with presumed no or unknown risk factors we previously reported, average BMI was 27.9 kg/m2. This is in the absence of any clinical and/or radiologic alleged criteria for a diagnosis of MASH. In the presence of subtle clinical and/or radiologic findings suggestive of MASH, evaluating patient’s BMI may be considered as an added variable for evaluation of patients with HCC. We clinicians need to be aware of increased BMI as a possible prelude for MASH and HCC. This is added to an invitation for acquired biopsies to include tumor and normal tissue to assess liver cirrhosis or fibrosis.
Factors associated with the receipt of palliative care in Native American patients with hepatocellular carcinoma: A retrospective analysis.
Authors: Dentinger Lauren , Kolluru Sowmya Prathika , Bine Christopher Reese , Silberstein Peter T.
Published: July 2024

e16202

Background: Hepatocellular Carcinoma (HCC) is a leading cause of cancer-related deaths in the United States. This primary liver malignancy often has a poor prognosis and commonly metastasizes to the lungs, lymph nodes, bones, and adrenal glands. HCC has a high burden of disease with many patients suffering from discomfort and pain related to the disease and its treatment. Palliative care is a unique form of specialized care that provides relief, increasing comfort, and quality of life to patients suffering from illness. Many studies note its effectiveness in helping patients at any point in their illness. Furthermore, recent studies have shown that Native Americans face barriers to receiving palliative and end of life care. Thus, this study aims to examine the factors associated with receipt of palliative care within Native American HCC patients. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with Hepatocellular Carcinoma from 2004 to 2019 using the histology code 8170 and race code 03 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Cox Proportional Hazards tests were performed. Data was analyzed using SPSS version 28 and statistical significance was set at α = 0.05. Results: Out of 1536 Native American patients with HCC, 92 (5.9%) received palliative care. Patients who received palliative care experienced shorter mean survival than those who did not receive palliative care (15 vs 42 months; p < 0.001). After controlling for age, year of diagnosis, surgical status and adjuvant therapies, not receiving palliative care was associated with an independent decrease in hazard (HR = 0.625, p < 0.05). Palliative care patients were more likely to present with stage III and IV HCC, experience a longer delay in receiving treatment (69 vs 48 days) and have bone and lung metastasis when compared to those who did not receive palliative care (p < 0.05). Patients who did not receive palliative care were more likely to have Medicare or Medicaid for insurance (p < 0.05). There were no significant differences in the age, income bracket, facility type, tumor size or time to surgery between the patients who received palliative care and those who did not. Conclusions: This study found that patients with HCC are more likely to utilize palliative care if they have severe disease that metastasized to other organ systems. There is a higher mortality among patients who receive palliative care most likely because they had more severe disease. This research demonstrates the common trend of HCC patients underutilizing palliative care in the early stages of disease. Exploring the impacts early palliative care can have on HCC patients’ survival and quality of life would be valuable future areas of research.
Primary and secondary resistance to immune checkpoint inhibitors in hepatocellular carcinoma.
Authors: Cui Xiaowen , Ruan Minghao , Li Yao , Yang Cheng , Zhou Liuyu , Zhang Jin , Jin Riming , Wu Dong , Wang Ruoyu
Published: July 2024

e16209

Background: Immunotherapy have revolutionized the therapeutic landscape of hepatocellular carcinoma (HCC). However, clinical features affecting immune resistance remain largely unknown. This retrospective cohort study aims to investigate the outcomes and characteristics of pts with resistance to immunotherapy in HCC. Methods: Pts with HCC who received immune checkpoint inhibitors (ICIs) of PD-1/PD-L1 antibodies at Eastern Hepatobiliary Surgery Hospital between 2016 and 2021 were retrospectively enrolled and screened for eligibility. Recommended by the Society for Immunotherapy of Cancer (SITC), primary resistance was defined as when pts were exposed to ICIs therapy for at least 6 weeks and with the best overall response (BOR) of PD or SD for less than 6 months. Secondary resistance was defined as pts having disease progression after the initial objective response (CR/PR) or SD for more than 6 months. The durable response group consists of pts with the durable response (CR, PR, or SD) for more than 6 months without progression at data cutoff. Time to progression (TTP), overall survival (OS) and clinicopathological features of HCC pts were compared between groups. Subsequent management after resistance and post-progression survival (PPS) were also analyzed. Results: Of 496 pts included, 229 (46.2%) and 141 (28.4%) pts developed primary resistance and secondary resistance, and 126 (25.4%) pts achieved a durable response. The median follow-up was 22.8 months. For pts with primary resistance, secondary resistance, and durable response, the median TTP was 2.83 [2.56-3.09] months, 11.93 [10.45-13.40] months, and not reached, respectively. Whereas the median OS was 12.83 [10.36-15.30] months, 31.53 [28.09-34.97] months and not reached, respectively. Multivariate logistic regression revealed that the Child-Pugh score (Child-Pugh B versus A, OR 3.28 [1.51-7.13], p= 0.003), BCLC stage (BCLC B versus A, OR 3.55 [1.70-7.43], p= 0.001; BCLC C versus A, OR 2.88 [1.47-5.65], p= 0.002), and combinational therapies (ICIs+bevacizumab versus monotherapy, OR 0.14 [0.04-0.51], p= 0.003; ICIs plus lenvatinib+monotherapy, OR 0.43 [0.26-0.72], p= 0.001) were independently associated with primary resistance, and only the combination of ICIs plus bevacizumab (ICIs+bevacizumab versus monotherapy, OR 0.10 [0.01-0.52], p= 0.007) was independently associated with secondary resistance. AFP levels and post-progression therapies were independently associated with PPS in pts with primary resistance, while post-progression therapies were independently associated with PPS in pts with secondary resistance. Conclusions: Risk for resistance was significantly lower among pts who received ICIs plus bevacizumab.High AFP levels independently predict the survival of pts after primary resistance to immunotherapy. ICI-based maintenance therapy after resistance may provide a significant survival advantage for HCC pts.
Fibrolamellar hepatocellular carcinoma (FL-HCC) epidemiology, survival characteristics, and outcomes: Surveillance, epidemiology, and end results database (SEER) study.
Authors: Alnabulsi Zaid , Batra Nitya , Khosla Atulya Aman , Attia Abdelrahman M. , Kiryakoza Morgan , Deb Novonil , Ezekwudo Daniel
Published: July 2024

e16213

Background: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare and distinctive form of liver cancer that primarily affects adolescents and young adults without underlying liver disease. Unlike conventional HCC, it exhibits unique clinical and histological features and poses a diagnostic and therapeutic challenge. Using a national registry, we sought to evaluate the incidence, demographics, survival, and treatment characteristics of FL-HCC. Methods: We utilized the Surveillance, Epidemiology, and End Results (SEER) database to identify patients with microscopically confirmed FL-HCC between 2000-2020 using ICD-O-3 site code C22.0 and an 8171/3 histology code. The epidemiological characteristics included were age, gender, ethnicity, American Joint Committee on Cancer [AJCC] staging, annual income, and treatment modalities. The Kaplan-Meier survival curve was used to compare survival. Survival was stratified according to age, gender, race, stage, income, and treatment modalities. Multivariate analysis was done with Cox regression analysis on R programming language version 3.6.3. Results: We identified a total of 362 patients with fibrolamellar hepatocellular carcinoma with median age at diagnosis 27(8-84) years. It was found to be more common in males (62.2%) and among whites (78.2%). There was a striking increment in incidence with 1.9% in 2005 compared to 5.8% in 2020. The majority of the patients had stage IV disease (26.4%). Alpha-fetoprotein was noted to be positive only in 15.8% of patients. The majority of the patients received surgery (50.3%) and chemotherapy (48.1%) with a median time from diagnosis to treatment of 1.00 month (IQR: 0.00–1.00). A total of 11% of patients received radiation, and 25% received multiple treatments. Survival analysis revealed a median overall survival of 24.50 months (IQR: 7.00, 63.00), with a majority experiencing death attributable to the cancer diagnosis (60.2%). Median overall and cause-specific survival for stage I disease was 92 months, and stage IV disease was 21 months (p < 0.05). Patients below the age of 20 had a median survival of 85 months (95% CI: 41 to NA) compared to those aged between 20 and 59, i.e., 30 months (95% CI: 22 to 41 months). The higher-income categories, $55,000−59,999 (HR = 0.29, p = 0.05) and $60,000−64,999 (HR = 0.24, p = 0.03), demonstrated significantly lower hazards compared to < $35,000. We concluded that sex, location, and race did not influence the survival of FL-HCC. Conclusions: Our comprehensive analysis of FL-HCC revealed that diagnosis at a younger age, stage I disease, and higher annual income improved survival, whereas gender and race did not affect outcomes. Further collaborative efforts are warranted to advance our understanding of FL-HCC pathogenesis, optimize treatment strategies, and improve outcomes for affected individuals.
Prognostic significance of real-world (RW) recurrence patterns after resection or ablation of early-stage hepatocellular carcinoma (HCC): Insights from the US Medicare population.
Authors: Maithel Shishir K. , Wang Rongrong , Harton Joanna , Yopp Adam C. , Shah Shimul , Rocha Flavio G. , Hernandez Sairy , Cheng Spencer , Ogale Sarika , Tan Amie
Published: July 2024

e16241

Background: The prognosis after curative-intent resection or ablation of early-stage HCC remains poor, largely due to high rates of recurrence. We aimed to characterize real-world recurrence patterns and determine whether the timing of recurrence was associated with overall survival (OS). Methods: Patients (pts) with early-stage HCC who underwent resection and/or ablation were identified from the SEER-Medicare database (2010-2019). Pts who received liver transplant were excluded. A proxy for recurrence was defined as the receipt of new HCC treatments (surgery, locoregional therapy, systemic therapy) or a secondary malignant neoplasm claim (excluding liver). Pseudo-recurrence dates were assigned to pts without recurrence to match the distribution of time between initial resection/ablation and recurrence in the recurrence cohort, to avoid immortal time bias. Early vs late recurrence was defined as occurring within 1 year vs after 1 year of initial resection/ablation. Primary outcome was OS as measured both from the time of recurrence/pseudo-recurrence and initial resection/ablation. Results: 1,146 eligible pts with early-stage HCC were identified. 63% were male, mean age was 74 yrs, and initial therapy was resection (39%), ablation (50%), or both (11%). 736 (64%) experienced recurrence. Among them, 53% received ablation, 37% surgery, and 11% received both. Median OS from recurrence or pseudo-recurrence was 22 months (mo) vs 67 mo (p < 0.001) for pts with vs without recurrence, respectively. When measured from resection/ablation date, median OS was 39 mo vs 83 mo (p < 0.001). After adjusting for relevant demographic and clinico-pathologic factors, including type of index therapy, in a multivariable Cox regression model, recurrence remained significantly associated with an increased risk of death (hazard ratio [HR]: 2.24; 95% CI: 1.85-2.71; p < 0.001). Among pts who recurred, 380 (52%) had early recurrence and 356 (48%) had late recurrence. Median OS from recurrence was 17 mo vs 30 mo (p < 0.001) for early vs late recurrence, respectively, and 23 mo vs 63 mo when measured from resection/ablation The adjusted HR for the risk of death associated with early recurrence was 1.39 (95% CI: 1.14-1.68; p < 0.001) compared to late recurrence. Other significant prognostic factors associated with reduced OS included larger tumor size ( > = 5cm), greater extent of disease, and poor differentiation (grade III and above). Conclusions: In this study among US Medicare pts, early recurrence within one year after curative-intent treatment of early-stage HCC was significantly associated with decreased OS compared to pts who recur later or without recurrence. This highlights the need for developing and utilizing effective adjuvant therapy regimens to delay or avoid recurrence.
The efficacy and safety of donafenib-containing regimens as first-line therapy for hepatocellular carcinoma (HCC): A multicenter retrospective study.
Authors: Zhang Qingqiao , Yin Guowen , Xu Qingyu , Xiao Jinchang , Shen Bin , Chen Guofeng , Zhang Genshan , Feng Wei , Yang Yong , Hu Jianping , Wang Chenghu
Published: July 2024

e16243

Background: HCC is a common malignant tumor worldwide, safer and more potent treatments are desperately needed to increase the survival rates of HCC patients. Some studies have shown that transcatheter arterial chemoembolization/hepatic arterial infusion chemotherapy (TACE/HAIC) combined with systemic therapies shows potential synergistic effects in patients with HCC, the ZGDH3-III RCT's findings showed that donafenib(D) is highly safe and effective as first-line treatment for uHCC. This study aimed to evaluate the efficacy and safety of donafenib-containing regimens (D+TACE/HAIC, D+TACE/HAIC+ICI, D+ICI, D) as first-line systemic treatments for HCC patients in the real world. Methods: We retrospectively analyzed patient data from January 2022 to December 2023 in seven Chinese institutions with first-line therapeutic regimens based on donafenib. Donafenib-based treatments were administered to eligible patients until the point of disease progression, death, or intolerable toxicity. We examined the progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) per the modified Response Evaluation Criteria in Solid Tumors, and safety (CTCAE5.0). Results: There were 102 patients in this study (Table). The median age was 60 years (IQR: 52, 68) at the data cut-off in January 2024, with 87.3% of the population being male and 78.4% having HBV infection. Most patients received D+TACE/HAIC therapy (59.8%), D+TACE/HAIC+ICI therapy (35.3%), or other treatments. Median PFS and OS not yet been achieved, respectively, the 12-month PFS and OS rates were 87.0% (95%CI: 79.7%-95.0%) and 91.4% (95%CI: 84.9%-98.4%). The ORR was 68.6% and DCR was 88.2%, with complete response in 14 patients, partial response in 56 patients, stable disease in 20 patients, and progressive disease in 12 patients. Among the population, 51 patients (50.0%) had treatment-related adverse events (TRAE) of any grade, and the incidence of grade 3 TRAE was 13.7% (14/102), none of the patients experienced grade 4 or 5 TRAE. Conclusions: These results preliminarily showed that donafenib-containing treatment regimens exhibited encouraging efficacy and favorable safety profile in patients with HCC. [Table: see text]
Adjuvant tislelizumab combined with capecitabine for patients with biliary tract cancer with high risk of postoperative relapse (ACTIVE): Primary analysis from a prospective cohort study.
Authors: Yang Luyu , Lu Lu , Wang Xiangyu , Sun Haoting , Zhu Ying , Xu Da , Yang Jimeng , Yin Baobing , Yang Xin , Zhu Wenwei , Jia Huliang , Chen Jinhong , Qin Lunxiu
Published: July 2024

e16248

Background: Only 20% of biliary tract cancer (BTC) patients are eligible for surgical resection with curative intent, with 5-year overall survival of less than 10% for all patients. This rate is even lower in patients with high-risk features. Capecitabine as an adjuvant therapy in biliary tract cancer has been verified to improve overall survival, however, the efficacy still remains limited. PD-1/L1 antibody combined with chemotherapy have been demonstrated to improve survival in advanced biliary tract cancer. This study aimed to evaluate the efficacy and safety of adjuvant tislelizumab and capecitabine following surgery for biliary tract cancer with high risk of recurrence. Methods: This was a single-center, prospective cohort phase II study. BTC patients (pts) underwent R0/R1 resection with high postoperative recurrence risk were eligible. The high-risk factors included positive resection margins, positive lymph nodes, positive perineural invasion, and tumor > 5cm in diameter. The patients were divided into two groups, the tislelizumab (TIS 200 mg Q3W for 1 year )+capecitabine (CAP D1-14, 1500mg/m2 for eight 3-weekly cycles) group and the capecitabine group. The primary endpoint was DFS (disease free survival). The second endpoints was OS (overall survival) and adverse event (AE). Results: A total of 37 pts were enrolled into the study, while 22 pts in the TIS+CAP group and 15 in CAP group, 23 males and 14 females with a median age of 66 years. According to the location of the tumor, 37.8% pts were intrahepatic cholangiocarcinoma, 21.6% were gallbladder cancer, 5.4% were distal cholangiocarcinoma and 35.1% were hilar cholangiocarcinoma. The median DFS was 16.2 months (95% CI, 8.1-26.2) in the TIS+CAP group, which was longer than CAP group (11.4 months, 95% CI 4.2-27.1). 12-month RFS rates were 56.5% and 36.6% , respectively. The most common adverse events (AEs, any grade) were rash (18.2%), vomiting (13.6%), neutropenia (13.6%) and anorexia (13.6%) in the TIS+CAP group. Conclusions: Tislelizumab in combination with capecitabine were effective and safe as adjuvant therapy, which can prolong the DFS of BTC patients with high recurrence risk after resection. Clinical trial information: NCT04782804 .
Long-term survival outcomes with regular recurrence surveillance following surgical resection in early-stage hepatocellular carcinoma: Insights from a multicenter prospective study.
Authors: Yang Tian , Yao Lan-Qing , Liu Han , Diao Yong-Kang , Wu Yi-Fan , Li Chao , Liang Ying-Jian , Zeng Yong-Yi , Wang Ming-Da , Shen Feng , Lv Guo-Yue
Published: July 2024

e16259

Background: While surgical resection stands as the primary curative approach for early-stage hepatocellular carcinoma (HCC), the looming risk of recurrence significantly impacts long-term outcomes. This study investigates the influence of regular recurrence surveillance on the long-term prognosis of HCC patients after curative surgical resection. Methods: In this large multicenter observational study, patients who underwent curative resection for early-stage (BCLC stage 0/A) HCC were divided into two cohorts: those adhering to a structured surveillance protocol (regular check-ups every 2-3 months for the first two years, followed by biannual check-ups) and those with irregular or no recurrence surveillance. Key metrics compared between these groups included overall survival (OS), time-to-recurrence (TTR), and post-recurrence survival (PRS). Results: The study encompassed 1,544 patients, with 786 (50.9%) adhering to regular surveillance for postoperative recurrence. Patients under regular surveillance, as opposed to those with irregular/no surveillance, demonstrated a comparable TTR (median: 61.4 vs. 66.2 months, P = 0.161). However, they exhibited significantly improved OS (median: 113.4 vs. 94.5 months, P = 0.010) and PRS (median: 37.9 vs. 16.3 months, P < 0.001) in cases of recurrence. Multivariable Cox-regression analysis identified regular recurrence surveillance as an independent protective factor, significantly enhancing OS (HR: 0.777; 95% CI: 0.663-0.910; P = 0.002) and PRS (HR: 0.523; 95% CI: 0.428-0.638; P < 0.001). Conclusions: Regular recurrence surveillance markedly improves OS and PRS in patients undergoing surgical resection for early-stage HCC. This study underscores the critical importance of adherence to a structured surveillance regimen in HCC management, potentially enhancing opportunities for subsequent curative interventions and improving long-term survival outcomes. [Table: see text]