bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of a cancer tracking system on timeliness of liver cancer care at a Veteran's Hospital.
Authors: Ivatorov Amanda , Mezzacappa Catherine , Taddei Tamar Hamosh 
Published: January 2022

406 Background: Hepatocellular carcinoma (HCC) requires complex care coordination with opportunities for care delays and untimely follow-up of abnormal liver imaging results. An electronic medical record-linked abnormal imaging identification and tracking system was implemented at a Veterans Affairs Hospital. The system reviews all liver radiology reports, generates a queue of abnormal cases for care coordinator review, and provides a tracking feature to monitor each patient’s care. Methods: This is a pre-/post-intervention study to evaluate whether implementation of this tracking system reduced (1) time between HCC diagnosis and treatment and (2) time from first suspicious image to first specialty care appointment, diagnosis, and treatment. Patients diagnosed with HCC in the 37-months before tracking system implementation (pre-intervention) were compared with patients diagnosed with HCC in the 71-months (less an 11-month grace period) after tracking system implementation (post-intervention). Linear regression was used to calculate mean change in relevant intervals of care pre- and post-intervention adjusted for patient age, race, ethnicity, BCLC stage at diagnosis, and indication for first suspicious image. Results: There were 60 patients in the pre-intervention period and 127 in the post-intervention period. The post-intervention group had a greater proportion of HCC diagnosed at earlier BCLC stages (p<0.03). Compared to the pre-intervention cohort, the post-intervention cohort had an adjusted mean reduction of 36 days from diagnosis to treatment (p=0.007), 51 days from suspicious imaging to diagnosis (p=0.21), and 87 days from suspicious imaging to treatment (p=0.05). Stratified by indication for first suspicious imaging, patients whose imaging was performed for HCC screening had the greatest decreases in time from diagnosis to treatment (63 days, p=0.02) and from first suspicious image to treatment (179 days, p=0.03). Conclusions: Our tracking system improved timeliness of HCC diagnosis and treatment. We anticipate it may improve HCC care coordination and delivery, including when added to HCC screening protocols.[Table: see text]
Regorafenib plus nivolumab as first-line therapy for unresectable hepatocellular carcinoma (uHCC): Multicenter phase 2 trial (RENOBATE).
Authors: Yoo Changhoon , Ryoo Baek-Yeol , Kim Hyung-Don , Ryu Min-Hee , Kang Beodeul , Chon Hong Jae , Hong Jung Yong , Lim Ho Yeong 
Published: January 2022

415 Background: The immunomodulatory effect of regorafenib may enhance the anti-tumor activity of nivolumab in patients with uHCC. We report results from a phase 2 study of regorafenib plus nivolumab as first-line therapy in patients with uHCC. Methods: In this open-label, multi-center, single-arm study, patients with >19 years, ECOG PS 0 or 1, BCLC stage B or C, and no prior systemic therapy were eligible. Patients received intravenous nivolumab 480 mg, every 4 weeks, and oral regorafenib 80 mg daily, 3 weeks on/1 week off, every 4 weeks. Tumor response was evaluated per RECIST v1.1, every 8 weeks (fixed schedule). Primary endpoint was overall response rates (ORR) per RECIST v1.1. Secondary endpoints were progression-free survival (PFS), overall survival (OS), ORR per mRECIST, and safety profile per NCI-CTCAE v5. Results: A total of 42 patients were enrolled between JUL-2020 and JAN-2021. Median age was 61 years (range, 40-79), and 31 patients (73.8%) were male. Most patients had BCLC C stage (n=38, 90.5%) and hepatitis B virus infection (n=30, 71.4%). Extrahepatic metastasis was noted in 36 patients (85.7%) and baseline serum AFP levels were >400 ng/mL in 17 patients (40.5%). With median follow-up duration of 9.2 months (95% CI, 8.5-9.9 months), 21 patients were ongoing in this study. ORR per RECIST v1.1 was 31.0% (CR 1 [2.4%] and PR 12 [28.6%]), and ORR per mRECIST was 35.7% (CR 4 [9.5%] and PR 11 [26.2%]). Median PFS was 5.5 months (95% CI, 1.8-9.1 months) and median OS was not reached. The 6-months PFS and OS were 49.9% and 90.4%. Most common adverse events were hand-foot skin reaction (n=14, 33.3%), skin rash (12, 28.5%), and alopecia (10, 23.8%). Conclusions: Regorafenib plus nivolumab shows promising efficacy outcomes in uHCC. There was no unexpected safety signals and most of toxicities were manageable. Clinical trial information: NCT04310709.
Transcatheter arterial chemoembolization therapy in combination strategy with lenvatinib in patients with unresectable hepatocellular carcinoma (TACTICS-L) in Japan: Final analysis.
Authors: Ueshima Kazuomi , Ishikawa Toru , Saeki Issei , Morimoto Naoki , Aikata Hiroshi , Tanabe Nobukazu , Inaba Yoshitaka , Wada Yoshiyuki , Kondo Yasuteru , Tsuda Masahiro , Nakao Kazuhiko , Ikeda Masafumi , Moriguchi Michihisa , Ito Takanori , Kobayashi Masahiro , Koga Hironori , Hino Keisuke , Suzuki Yoshiyuki , Yoshimura Kenichi , Kudo Masatoshi 
Published: January 2022

417 Background: Treatment options for hepatocellular carcinoma (HCC) include surgical resection, percutaneous ablation therapy, transcatheter arterial chemoembolization (TACE), and liver transplantation, etc., and TACE is indicated for unresectable HCC (uHCC) that is not eligible for curative therapy. Combination therapy with TACE and molecular targeted agents has been reported to have higher antitumor efficacy than respective monotherapies. This study aims to evaluate safety and efficacy of combination of TACE and lenvatinib in uHCC patients. Methods: Phase II, prospective, multicenter, single-arm study was conducted in 19 Japanese sites. Lenvatinib was administered orally once daily for 14 to 21 days prior to TACE at a dose of 12 mg (body weight ≥60 kg) or 8 mg (< 60 kg). The first TACE was performed after a 2-day lenvatinib withdrawal period. This combination therapy was repeated until the time to untreatable progression (TTUP). The primary endpoint was progression-free survival (PFS). Secondary endpoints included TTUP, objective response rate (ORR), overall survival (OS), and safety. Results: Between February 2019 and April 2020, 62 patients were enrolled. Median age was 72.0 years (< 65 years, 13 [21.0%]; ≥65 years, 49 [79.0%]). Number of patients with Child-Pugh score 5 and 6 was 51 (82.3%) and 11 (17.7%); Eastern Cooperative Oncology Group Performance Status 0 and 1 was 59 (95.2%) and 3 (4.8%); and Barcelona Clinic Liver Cancer Stage A and B was 25 (40.3%) and 37 (59.7%). The number of previous TACE procedures was 0 in 35 patients (56.5%) and 1 to 3 in 27 patients (43.5%). The estimated median PFS, OS, and TTUP were more than 2 years. The ORR was 88.7% (90% CI 79.8 – 94.6 with complete response (CR) rate of 66.1%). Treatment emergent adverse events (AEs) occurred in 98.4% of patients, and the most common AEs were hypothyroidism (58.1%), hypertension (53.2%), decreased appetite (50.0%), and fatigue (48.4%). Grade 3 and 4 AEs occurred in 71.0% and 4.8%, and serious AEs occurred in 40.3%. One death not causally related to the protocol treatment was observed. Conclusions: In this final analysis, the combination of TACE and lenvatinib showed promising therapeutic efficacy in patients with uHCC. No new safety signal was observed. Future phase III studies are required to validate this combination therapy. Clinical trial information: jRCTs031180074.
Clinical outcomes associated with tislelizumab in patients (pts) with advanced hepatocellular carcinoma (HCC) who have been previously treated with sorafenib (SOR) or lenvatinib (LEN) in RATIONALE-208.
Authors: Edeline Julien , Merle Philippe , Fang Weijia , Assenat Eric , Pan Hongming , Rimassa Lorenza , Li Zhiwei , Blanc Jean-Frederic , Yen Chia-Jui , Ross Paul J. , Hu Sheng , Zhang Tao , Tran Albert , Shao Guoliang , Bouattour Mohamed , Chen Yajin , Wu John , Li Bai , Chica-Duque Sandra , Ren Zhenggang 
Published: January 2022

420 Background: Tislelizumab, an anti-PD-1 monoclonal antibody, demonstrated clinical activity and was well tolerated in pts with previously treated advanced HCC in the phase 2 RATIONALE-208 study (NCT03419897). At the time of this study, SOR and LEN were recommended first-line treatments for pts with advanced HCC and continue to have an important role in the first-line treatment of HCC despite the recent approval of new immuno-oncology-based combinations (atezolizumab and bevacizumab) in some regions. We report the clinical outcomes of pts with advanced HCC who were previously treated with SOR/LEN. Methods: Pts who had received ≥1 prior line of systemic therapy for advanced HCC received tislelizumab 200 mg intravenously once every three weeks. Objective response rate (ORR) by independent review committee (IRC) (ORRIRC), duration of response by IRC (DORIRC), progression-free survival by IRC (PFSIRC), overall survival (OS), and safety were evaluated in pts who had been previously treated with SOR/LEN. Results: As of February 2020, 249 pts were enrolled and 235 pts had received prior treatment with SOR/LEN, of whom 126 and 109 pts had received 1 or ≥ 2 prior lines of systemic therapy, respectively. At study entry, 211 (89.8%) pts had BCLC stage C and 187 (79.6%) pts had extrahepatic spread. Median follow-up duration for pts previously treated with SOR/LEN was 12.5 months and ORRIRC was 13.6% (95% CI: 9.5, 18.7), including 2 complete responses and 30 partial responses. Median DORIRC was not reached. Median PFSIRC and OS of pts previously treated with SOR/LEN was 2.7 months (95% CI: 1.6, 2.8) and 13.5 months (95% CI: 10.9, 15.8), respectively. Tislelizumab was generally well tolerated in pts previously treated with SOR/LEN (Table), and the most common treatment-emergent adverse events were increased aspartate aminotransferase (n=70; 28.1%) and alanine aminotransferase (n=52; 20.9%). Conclusions: Tislelizumab was investigated beyond the first-line setting, as effective second- and third-line treatment options are limited for pts with advanced HCC and there is an unmet medical need. This analysis indicates that tislelizumab is clinically active and well tolerated in pts with advanced HCC who have received prior systemic treatment with SOR/LEN. Clinical trial information: NCT03419897. [Table: see text]
A study of pembrolizumab (pembro) in combination with Y90 radioembolization in patients (pts) with poor prognosis hepatocellular carcinoma (HCC) with preserved liver function.
Authors: McRee Autumn Jackson , Helft Paul R. , Harris William Proctor , Sanoff Hanna Kelly , Johnson Matthew , Yu Menggang , O'Neil Bert 
Published: January 2022

422 Background: HCC is an aggressive cancer that is challenging to treat due to the concomitant diagnosis of cirrhosis. For HCC pts with no extrahepatic metastases and well-compensated liver function, Y90 radioembolization is a standard therapy. In observational studies, pts with multifocal disease or portal vein thrombosis (PVT) had worse outcomes with short disease control intervals of less than 6 months. Pembro is an anti-PD-1 monoclonal antibody that is FDA-approved for advanced HCC pts who have progressed on sorafenib. Given pre-clinical evidence that radiotherapy can increase PD-L1 expression and enhance tumoral T-cell recruitment, this study explored the safety and efficacy of pembro with Y90 radioembolization in pts with poor prognosis HCC. Methods: GI15-225 was a multi-center, single-arm study in poor prognosis HCC pts, defined as having multifocal disease, branch PVT and/or diffuse disease (NCT03099564). Pts with extrahepatic metastatic disease were excluded; eligible pts had disease amenable to 1-2 embolization procedures. Pts had Child Pugh A/B7 cirrhosis with no prior Y90 treatment; previous TAE, TACE, SBRT, liver resection or ablation were allowed. Treatment consisted of pembro 200mg every 3 weeks with Y90 radioembolization performed 7-10 days after first dose of pembro. The primary objective was to estimate the progression free survival (PFS) rate at 6 months per RECIST 1.1; secondary endpoints included safety, time to progression (TTP), overall response rate (ORR) and overall survival (OS). Results: A total of 29 pts were enrolled 10/23/17 to 11/24/20. Median age 66 years, 89% male, and 47% with PVT. 26 pts were evaluable for primary endpoint having received Y90 and at least one dose of pembro. The 6 month PFS rate was 57.7% (95% CI 36.9 – 76.6). Median PFS was 8.6 months (95% CI 4.1 – 13.4) and median TTP was 9.9 months (95% 4.2 – NR). Median OS was 22 months (95% CI 8.4 – 32.0). The ORR was 27% (Table). Most common treatment related grade 3-4 AEs were decreased lymphocytes (18%), increased bilirubin (11%), hypertension (11%), ascites (7%), and AST/ALT elevation (7%). One pt experienced grade 5 toxicity of hepatic failure after receiving one dose of pembro and Y90 that was attributed to Y90 and disease progression. Conclusions: Concurrent administration of pembro with Y90 radioembolization in pts with poor prognosis HCC demonstrated promising clinical activity with median TTP and OS that exceeds historical data reported in similar patients treated with Y90 alone. With a 6 month PFS rate of 57.7% and a favorable toxicity profile, the combination of immune checkpoint blockade and Y90 deserves further evaluation in larger randomized clinical trials. Clinical trial information: NCT03099564. [Table: see text]
Radio-immunotherapy for advanced HCC: A pilot study of irradiation dose.
Authors: Su Ting-Shi , Li Jian-Xu , Li Li-Qing , Xiang Bang-De , Liang Shi-Xiong 
Published: January 2022

426 Background: Preclinically, radiation therapy for tumors was well known to reverse the immunosuppressive state by reprograming the tumor microenvironment. The combination of radiotherapy and immune checkpoint inhibitors (radio-immunotherapy) has renewed interest in clinical practice, and different irradiation dose may contribute diversely to immune response and abscopal effect. This pilot study aimed to assess the antitumour activity of the anti-PD-1 inhibitor Camrelizumab combined with different irradiation dose in patients with advanced hepatocellular carcinoma (HCC). Methods: Between April 2020 and January 2021, 20 patients with advanced HCC were prospectively enrolled in this pilot study. Five patients were treatment-naive and 15 patients were diagnosis as progressive diseases after previous treatment. For each patient, one to 3 intrahepatic and/or extrahepatic lesions were selected to irradiate. Camrelizumab was concurrently administered with 200mg on the first day of radiation and then every 3 weeks until disease progression, or unacceptable toxicity. Eligible patients were randomly assigned to receive 3 irradiation doses: low-dose group of 30Gy/10 fractions(3Gy/fx), intermediate-dose group of 40Gy/10 fractions (4Gy/fx), and high-dose group of 50Gy/10 fractions (5Gy/fx). Results: Nine patients had intrahepatic lesions (8 of macrovascular invasion) and 11 had extrahepatic metastases. The median number of treatment lines receiving immunotherapy of Camrelizumab was 2 (range 1-5). Enrolment to the 30Gy group was halted after 2 patients due to the poor clinical response. Finally, 2, 11, and 7 patients received the irradiation dose of 30, 40, and 50Gy, respectively. Twenty-eight selected lesions were irradiated (partial lesions in 12 patients and all lesions in 8 patients). Grade 3 treatment-related adverse events were observed in 4 patients, including 2 thrombocytopenia and 1 anaemia in the 40Gy group, and 1 anaemia in the 50Gy group. The median follow-up time was 12 months (range 7.0–18.0 months). There was a significant difference in PFS, but no difference in OS between the three groups. The median, 6- and 12-months PFS for the 30, 40, and 50 Gy groups were 1.7 months, 0% and 0% vs. 4.0 months (95%CI 1.7-6.3 months), 27.3% and 18.2% vs. 7.8 months (95%CI 4.1-11.5 months), 57.1% and 38.1%, respectively (P = 0.027). The median, 12-months OS were 11.4 months and 50% vs. 11.8 months and 34.6% vs. not reached and 66.7%, respectively (P = 0.229). The disease control rates were statistically different between the 30, 40, and 50Gy groups (50% vs. 54.5% vs. 100%, P = 0.039), whereas objective response rates were not significant different (0% vs. 45.5% vs. 71.4%, P = 0.123). Conclusions: Higher irradiation dose with 50 Gy in 10 fractions plus Camrelizumab may augment the radio-immunotherapy activity in advanced HCC with favorable PFS. The present study offers guidance for the dose selection of subsequent clinical trials. Clinical trial information: ChiCTR2000032375.
Nivolumab (NIVO) and drug eluting bead transarterial chemoembolization (deb-TACE): Updated results from an ongoing phase 1 study of patients (pts) with liver limited hepatocellular carcinoma (HCC).
Authors: Harding James J. , Yarmohammadi Hooman , Reiss Kim Anna , Chou Joanne F. , Capanu Marinela , Do Richard K. G. , Khalil Danny , El Dika Imane H. , Ferrer Christine S. , Heffernan Olivia , Giardina J Daniel , Merghoub Taha , Jarnagin William R. , Nadolski Gregory , Erinjeri Joseph Patrick , Soulen Michael C. , Tan Benjamin R. , Abou-Alfa Ghassan K. 
Published: January 2022

437 Background: TACE is a standard of care for liver limited HCC and impacts the immune microenvironment, potentially augmenting the effects of immune checkpoint inhibitors. Methods: This is a multicenter phase 1 study of NIVO and deb-TACE in unresectable HCC pts and Child Pugh A cirrhosis (NCT03143270). The primary objective is to assess safety. Secondary objectives include response rate by RECIST v1.1, progression-free and overall survival by Kaplan-Meier methodology, and blood/tumor immune correlates. A 3 + 3 design with expansion cohort sequentially evaluates 3 cohorts of differing schedules of NIVO relative to deb-TACE. Deb-TACE (75mg of doxorubicin) is administered on Day 0. NIVO is dosed at 240mg IV every 14 days for 1 year (Cohort 1: NIVO begins day +14 after deb-TACE; Cohort 2, interrupted NIVO dosing begins at Day -28 but is held on the Day 0 then restarted on Day +14; Cohort 3, continuous NIVO dosing begins on Day -28 without interruption). Results: As of September 2021, 19 pts were treated [median 67 years (range: 54-78), male (80%), ECOG PS 0 (47%), Child Pugh A (100%), 3 pts in each cohort 1 and 2, 13 pts in cohort 3]. No cases of treatment related liver failure or Grade 5 adverse events (AEs) were observed. 1 DLT of Grade 3 transaminitis was observed in cohort 3 and resolved without intervention and did not recur with drug rechallenge. Median ALT at baseline, day 28, day 56, and end of treatment (EOT) were 27, 43.5, 36.5, and 29 U/L. Median bilirubin at baseline, day 28, day 56, and EOT were 0.6, 0.6, 0.5, and 0.6 mg/dL. Mean ALBI score at baseline (N=19) and EOT (N=14) were -2.75 ± 0.48 vs. -2.55 ± 0.50. The most common treatment-related AEs of any grade were fatigue (53%), ALT/AST increase (42%), fever (37%), and pruritis (32%). The objective response rate by RECIST v 1.1 was 21% (Table). 5/19 pts remained on study with SD or better for ≥12 (range 12-43) months. Updated survival analysis will be presented at the meeting; correlatives at a separate venue. Conclusions: Nivolumab administered with deb-TACE is safe with antitumor activity. This study provides a needed benchmark for the safety of embolization along with anti-PD1 therapy in liver limited HCC. The clinical question of combining immunotherapy with embolization to improve outcome over embolization alone remains investigational and several, pivotal, phase 3 studies are ongoing. Clinical trial information: NCT03143270. [Table: see text]
The safety and efficacy of transarterial chemoembolization (TACE) + lenvatinib + programmed cell death protein 1 (PD-1) antibody of advanced unresectable hepatocellular carcinoma.
Authors: Zhang Xiaoyun , Zhu Xinrui , Liu Chang , Lu Wusheng , Li Qiu , Chen Weixia , Li Zhiping , Lu Qiang , Peng Wei , Li Chuan , Yan Lvnan , Yang Jiayin , Wen Tianfu 
Published: January 2022

453 Background: More than 70% of hepatocellular carcinoma (HCC) patients are in the intermediate or advanced stages at the time of diagnosis. TACE, TKI and PD-1 antibody are all recommended for patients with unresectable HCC (uHCC) according to Chinese HCC guidelines. There are few scientific trials to back up the safety and effecacy of TACE+TKI+PD-1 antibody for the treatment of uHCC and conversion resection. In this study, we explored the safety and efficacy of the TACE+TKI+PD-1 antibody in uHCC. Methods: This is a prospective, multicenter, cohort study (NCT04997850). Key Eligibility Criteria:18 years old ≤ age ≤ 70 years old; HCC confirmed by histopathology or cytology; No systemic treatment history. ECOG PS score 0-1; Child-Pugh A/B; BCLC stage B/C.Experience group: TACE + Lenvatinib (12mg when≥ 60kg/8mg when < 60kg QD) + Camrelizumab/ Sintilimab (200 mg ivgtt Q3W);Control group: TACE. Results: From Sep 2020 to May 2021, 38 patients were enrolled in experimental group (Table). At the cutoff date (Sep 10 2021), the median follow-up was of 33.34 weeks (Table). The conversion resection rate was 50% (19/38), and the conversion success rate was 52.6% (20/38). Among the 19 patients, 5 cases achieved complete pathological response and 1 case achieved major pathological response. The 48 weeks’ OS rate and PFS were 96.4% (95%CI 92.9% to 99.9%) and 91.7%(95%CI 85.8% to 97.4%).22 patients had level 3 treatment related adverse events (TRAE), there were no level 4 and 5 TRAEs. At the last follow-up, the ORR rate based on mRECIST was 84.2%, and the DCR rate was 94.7% (Table). Conclusions: TACE + Lenvatinib + PD-1 antibody is safe and effective, and conversion resection after the triple-treatment is feasible for uHCC. Clinical trial information: 04997850.[Table: see text]