bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of clinical and tumor characteristics on survival in patients with hepatocellular carcinoma with bone metastasis.
Authors: Ozer Muhammet , Goksu Suleyman Yasin , Fabregas Jesus C. , Ramnaraign Brian Hemendra , Rogers Sherise C. , George Thomas J. , Sahin Ilyas 
Published: January 2023

525 Background: Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and the incidence of liver cancer is rapidly rising in the United States. Advanced HCC generally has a dismal prognosis with an expected survival of less than 1 year. Bone metastases from HCC are infrequent with a poorer prognosis. However, the factors influencing their survival are not well-understood. We aimed to study the effects of clinical and tumor characteristics on survival in HCC patients with bone metastasis. Methods: We selected adult patients with HCC who had bone metastasis diagnosed between 2004 and 2019 using the National Cancer Database (NCDB). We described baseline characteristics using percentages. We performed the Kaplan-Meier method to calculate the median overall survival (OS). We included demographics (age at diagnosis, gender, race, insurance status), comorbidity score, and treatment characteristics. Results: Of a total of 3301 HCC patients with bone metastasis, 87.1% were male, and 12.9% were female. Among all, 72.2% were white, 19.3% were black, and 8.5% were others. A total of 59.9% of patients were <65 years. Eighty-six-point four percent of the patients had a total Charlton-Deyo comorbidity score of <3 and 13.6% had it ≥3. Among patients with known tumor grade, 25.4% had well differentiated, 37.8% moderately differentiated, 35.4% poorly differentiated, and 1.2% undifferentiated tumors. In univariate analysis, patients with well-differentiated tumors had better OS compared to poorly differentiated tumors (5.4 mo vs. 3.3 mo, p<0.05). In treatment groups, both single and multi-agent chemotherapy as first-course therapy significantly improved OS compared to patients’ chemotherapy was not administered (6.8 mo vs. 2.1 mo; 8.9 mo vs. 2.1 mo, respectively). We found no mortality difference between age, gender and race groups. Conclusions: In this cohort analysis of NCDB data, we report better OS in treatment receipt, lower tumor grade, and lower comorbidity score in HCC patients with bone metastasis. Previous studies of HCC patients with bone metastasis have been limited by small sample sizes, and lack of nationwide oncology outcomes data. Further large-scale prospective studies are needed.
Report of adverse events of special interest (AESIs) for sintilimab plus a bevacizumab biosimilar (IBI305) in unresectable hepatocellular carcinoma.
Authors: Ren Zhenggang , Xu Jianming , Bai Yuxian , Xu Aibing , Cang Shundong , Du Chengyou , Liu Baorui , Li Qiu , Lu Yinying , Chen Yajin , Shao Guoliang , Guo Yabing , Chen Zhendong , Fan Jia 
Published: January 2023

530 Background: In the phase III Orient-32 trial (NCT03794440), sintilimab plus IBI305 demonstrated a meaningful improvement in overall survival (OS) and progression-free survival (PFS) vs. sorafenib (Sor) in patients (pts) with unresectable HCC. Here we report the AESIs for sintilimab and IBI305 in Orient-32. Methods: 571 eligible pts with unresectable HCC were randomly assigned (2:1) to receive either sintilimab plus IBI305 or Sor (400 mg orally twice daily), until disease progression or unacceptable toxicity. The co-primary endpoints were OS and independent radiological review committee (IRRC)-assessed PFS according to RECIST 1.1. AESIs were defined by the sponsor and reported without judgement of causality. Analyses explored the incidence and severity of AESIs as well as correlation between AESIs and efficacy. Results: The safety set included 402 pts in the sintilimab plus IBI305 group and 184 pts in the Sor group. At the data cutoff on Dec 30th, 2021, the median follow-up time was 26.7 months. Any AESIs (≥1%) for sintilimab plus IBI305 group and Sor group occurred in 77.9% pts and 53.3% pts, respectively. The incidence of treatment-related grade 3-4 AESI for sintilimab+IBI305 was 31.3% and treatment-related serious AESI was 13.9%. The most common any AESIs were proteinuria (61.7% ), hypertension (41.8%), hemorrhage (15.4%) and hyperthyroidism (14.2%) (Table). In the characteristics of baseline, ages can be a predictor of the onset of proteinuria, hypertension and hyperthyroidism. In addition, the occurrence of of proteinuria and hypertension can be a predictor for a better survival. Conclusions: AESIs for sintilimab and IBI305 were tolerable and manageable in Orient-32 trial. Further, the incidence and severity of AESIs were consistent with the known safety profiles of the individual agents. Clinical trial information: NCT03794440 . [Table: see text]
Triplets versus doublets in the treatment of right-sided metastatic colorectal cancer in real-world setting: A propensity-score weighting analysis.
Authors: Gil Mariana , Peixoto Renata D'Alpino , Passarini Thais , Mathias Maria Cecilia , Moraes Eduardo Dias de , Canedo Jorge Alexandre , Pereira Sabrina , Amorim Larissa , Prolla Gabriel , Freitas Laura , Costa e Silva Matheus , Ferreira Carlos G. M. , Ferrari Bruno Lemos , Garicochea Bernardo , Dienstmann Rodrigo , Gil Roberto Almeida , Jácome Alexandre A. 
Published: January 2023

55 Background: Right-sided metastatic colorectal cancer (mCRC) has a worse prognosis and the best first-line treatment is still uncertain. The aim of this study was to analyze progression-free survival (PFS) and overall survival (OS) comparing triplet versus doublet backbone chemotherapy in first-line setting for right-sided mCRC. Methods: Retrospective study evaluating 510 patients with mCRC who were treated in a private institution in Brazil from January 2011 to December 2019. Information of 118 patients with right-sided primary tumor was analyzed in this study. Demographic and clinical data were retrieved from electronic medical records. PFS and OS were calculated in months (m) using propensity-score weighting analysis (PSWA) due to expected disparity between the number of patients treated with triplet and doublet regimens. Variables used to balance patient groups were age; metastasectomy; primary tumor resection; bevacizumab use; BRAF and RAS mutation status. Results: The median follow-up was 31 months. Our population was mostly composed of elderly (64%) and female (52%) patients. First-line treatment with triplet backbone chemotherapy was done in 16 patients (14%). Primary tumor resection was done in 14% of the cases, 55% underwent metastasectomy, and 57% received anti-VEGF treatment. BRAF mutation was found in 9% of the patients and RAS mutation in 46%. After PSWA we found a significant better median PFS among patients treated with triplet regimen: 12.7m versus 8.9m compared to those receiving doublet backbone chemotherapy, with a hazard ratio of 0.64 (CI 95%: 0.42 – 0.97); p-value: 0.037. No significant difference was found in OS (29.8m versus 45.5m) between triplet and doublet therapy groups, respectively. Conclusions: In our study we found a significantly better PFS with triplet backbone chemotherapy in first-line setting for right-sided mCRC, encouraging the use of this regimen in treatment-naive selected patients. However, no difference in OS was found, probably due to subsequent treatments. PSWA is an acceptable and needed tool to enable retrospective real world studies involving treatments with expected uneven distribution. More studies are needed to answer the best strategy to target right-sided mCRC, which remains a challenge for oncologists, with unmet needs.
Outcomes by antibiotic use in participants with advanced biliary tract cancer treated with durvalumab or placebo plus gemcitabine and cisplatin in the phase 3 TOPAZ-1 study.
Authors: He Aiwu Ruth , Tan Benjamin R. , Suksombooncharoen Thatthan , Takahashi Hidenori , Chen Ming-Huang , Ostwal Vikas S , Oh Sang Cheul , Sezer Emel , Potemski Piotr , Rau Kun-Ming , Sirachainan Ekaphop , Li Junhe , Blanc Jean-Frédéric , Cohen Gordon , Żotkiewicz Magdalena , Rokutanda Nana , Oh Do-Youn 
Published: January 2023

550 Background: TOPAZ-1 (NCT03875235) is a double-blind, Phase 3 study of durvalumab (D), an immune checkpoint inhibitor (ICI), + gemcitabine and cisplatin (GC) in participants (pts) with advanced biliary tract cancer (BTC). D + GC improved overall survival (OS) in pts with advanced BTC versus placebo (PBO) + GC (Oh et al. NEJM Evid 2022). Use of antibiotics during ICI treatment has been correlated with poorer OS and progression-free survival (PFS; Jiang et al. Front Oncol 2022). Methods: Pts were randomized 1:1 to receive D (1500 mg) or PBO on Day 1 every 3 weeks (Q3W), + G (1000 mg/m2) and C (25 mg/m2) on Days 1 and 8 Q3W, for ≤8 cycles, followed by D or PBO monotherapy Q4W. This exploratory subgroup analysis of TOPAZ-1 assessed OS and PFS by systemic antibiotic use during the study (≥1 dose 14 days before first D/PBO dose to 14 days after last D/PBO dose). Hazard ratios (HRs) were estimated using an unstratified Cox proportional hazards model, adjusting for disease status (initially unresectable or recurrent) and primary tumor location (intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, or gallbladder cancer). Data cut-off at primary analysis was Aug 11, 2021. Results: The number (%) of pts using antibiotics during the study (D + GC, 167/341 [49.0%]; PBO + GC, 167/344 [48.5%]) was similar between treatment arms. In the D + GC arm, median OS (95% CI) was similar regardless of antibiotics use: 12.6 (9.7–14.8) months in pts with antibiotics use vs 13.0 (10.8–14.7) months in pts without (Table). In the PBO + GC arm, median OS (95% CI) was 10.3 (8.7–12.5) in pts with antibiotics use vs 12.1 (11.0–13.8) in pts without. OS HRs (95% CI) in D + GC vs PBO + GC were 0.78 (0.59–1.02) in pts with antibiotics and 0.81 (0.62–1.07) in pts without. Median PFS (95% CI) was 7.3 (6.5–7.7) months in pts with antibiotics use vs 7.2 (5.9–7.4) months in pts without in the D + GC arm and 5.7 (5.4–6.6) months vs 6.1 (5.6–7.3) months, respectively, in the PBO + GC arm (Table). PFS HRs (95% CI) were 0.70 (0.55–0.89) in pts with antibiotics use and 0.82 (0.65–1.03) in pts without. Conclusions: In the TOPAZ-1 study of D in BTC, no meaningful difference was found in OS or PFS for participants who received antibiotics during the study period compared with those who did not, and results were consistent with the primary analysis. These results support that people receiving D may be treated with antibiotics when clinically indicated. Clinical trial information: NCT03875235 . [Table: see text]
Efficacy and safety of envafolimab plus lenvatinib combined with TACE in unresectable hepatocellular carcinoma: An open-label, single-arm, phase 2 study—The CISLD-12 study.
Authors: Liang Tingbo , Chen Yiwen , Huang Xin , Hu Wendi , Li Xiang , Sun Junhui , Shen Yan , Zhang Min , Wu Jian , Gao Shunliang , Yu Jun , Que Risheng , Zhang Yun , Yang Fuchun , Xia Weiliang , Zhang Aibin , Tang Xiaofeng , Bai Xueli 
Published: January 2023

558 Background: Transarterial chemoembolization (TACE) is one of the standard treatments for patients with intermediate-stage hepatocellular carcinoma (HCC). The combination of immune checkpoint inhibitors (ICIs) and lenvatinib has shown to be an effective regimen in patients with unresectable HCC (uHCC). In this study, we aim to investigate the efficacy and safety of combination of Envafolimab (a novel, single-domain PD-L1 antibody) with Lenvatinib plus TACE in uHCC patients. Methods: This is a prospective, open-label, single-arm, phase 2 study. Adults with confirmed uHCC with BCLC stage B or C, Eastern Cooperative Oncology Group performance status 0 or 1, Child–Pugh scored ≤7 and no previous systemic treatment for HCC are eligible. Patients will receive Lenvatinib once daily plus Envafolimab every 3 weeks plus TACE. TACE will be conducted repeatedly every 6 weeks on demand according to investigators’ consideration, mainly based on the proportion of viable tumors. Imaging evaluation will be conducted every 6 weeks. The primary endpoint is objective response rate (ORR). Disease control rate (DCR), duration of response (DoR), progression free survival (PFS), overall survival (OS) and safety are evaluated as secondary endpoints (NCT05213221). Results: forty patients were consecutively enrolled from March, 2022 to September 2022. The median age was 54.5 years. At present, thirty-six patients were included for efficacy analysis, and forty for safety evaluation. Number of patients with BCLC stage B and C was 17(47.2%) and 19 (52.8%), respectively. 13 (36.1%) patients presented with portal vein tumor thrombus (PVTT) and 2 (5.6%) patient presented with hepatic vein tumor thrombus (HVTT). The ORR was 36.1% and 80.6%, and DCR was 77.8% and 83.3%, based on RECIST v1.1 and modified RECIST respectively. 11 patients reached the standard of conversion to resectable HCC and received radical resection. The most common TRAEs were elevated AST (75%), elevated ALT (65%) and leukopenia (42.5%). No treatment-related deaths occurred. The survival data are not mature at present. Conclusions: Envafolimab plus Lenvatinib combined with TACE is a promising and tolerable therapeutic regimen for patients with BCLC B/C unresectable HCC. Clinical trial information: NCT05213221 .
Nab-paclitaxel plus anti–PD-1 antibody as second-line treatment for advanced biliary tract cancer: An investigator-initiated phase 2 study (NapaSinti trial).
Authors: Li Xiaofen , Zhou Nan , Yang Yu , Gou Hongfeng 
Published: January 2023

564 Background: Biliary tract cancer (BTC) is a relatively rare but highly aggressive malignancy. Gemcitabine + cisplatin ±durvalumab is the standard first-line treatment for advanced BTC. But in second-line setting, there is no satisfactory regimen for most patients without specific genetic mutations. This prospective, single-arm, phase 2 study is conducted to investigate the efficacy and safety of second-line nab-paclitaxel combined with sintilimab in advanced BTC patients. Methods: Eligible patients are histologically confirmed local advanced or metastatic adenocarcinoma or cholangiocellular carcinoma in biliary tract; aged from 18 to 75 years; with a performance status and adequate organ function; with documented disease progression after prior gemcitabine or fluorouracil-based systemic chemotherapy; not received taxol drugs or immune checkpoint inhibitors treatment. Enrolled patients will receive nab-paclitaxel 125mg/m2 on day 1, 8 plus sintilimab 200mg on day 1, administered intravenously every three weeks. The primary end point is objective response rate (ORR). The secondary end points are progression free survival (PFS), overall survival (OS) and adverse reactions. Next-generation sequencing (NGS) is voluntary before treatment. Results: Up to September 2022, 24 BTC patients have been enrolled, including 22 patients available for efficacy evaluation. The ORR is 27.3% (6/22), including 1 complete response (CR) and 5 partial response (PR). Disease control rate is 63.6% (14/22). And median PFS is 5.63 months (95% CI: 1.92-9.35 months). Median OS from enrollment to death of any cause is 12.60 months (95%CI: 7.84-17.36 months). The frequent grade 3 drug-related adverse events are leukopenia (16.7%), anemia (12.5%), neutropenia (8.3%), peripheral neuropathy (8.3%). There is no grade 4 drug-related adverse event occurred. One patient has experienced grade 3 immunological colitis. 11 participants have received NGS testing, with 9 ones are available for efficacy evaluation. Among the 9 participants, 5 patients harbor TP53 mutation [2 evaluated as PR, 2 SD (stable disease) and 1 PD (progressive disease)]; 3 patients harbor genetic mutations associated with DNA damage response pathway (2 evaluated as PR and 1 PD); and 1 patient is in status of microsatellite instability-high (MSI-H) evaluated as PR. Conclusions: The preliminary results of NapaSinti trial propose a brand new and effective regimen as second-line treatment for advanced biliary tract cancer. NGS may become a hopeful tool for efficacy prediction. Clinical trial information: ChiCTR2100052118 .
Efficacy of pembrolizumab as first-line therapy in patients with mismatch repair–deficient metastatic colorectal cancer in relation to the metastatic site.
Authors: Saberzadeh Ardestani Bahar , Jones Jeremy Clifton , Hubbard Joleen M. , McWilliams Robert R. , Halfdanarson Thorvardur Ragnar , Shi Qian , Sonbol Bassam Bassam , Ticku Jonathan , Jin Zhaohui , Sinicrope Frank A. 
Published: January 2023

57 Background: Metastatic colorectal cancer (mCRC) with deficient DNA mismatch repair (dMMR) or microsatellite instability-high (MSI-H) show frequent and durable responses to programmed cell death -1 (PD-1) blockade. While the majority of these tumors are sporadics and observed in elderly patients, first-line data are limited to the KEYNOTE-177 study. Here, we report a consecutive series of elderly patients with dMMR mCRC treated with pembrolizumab in routine clinical practice that includes analysis of clinical outcome based on metastatic site. Methods: Patients with dMMR mCRC received first-line pembrolizumab (200 mg every 3 weeks) (N = 41) at Mayo Clinic and Mayo Clinic Health System (2015-2022). Clinicopathological features including metastatic site and molecular data ( BRAFV600E, KRAS) were analyzed in relationship to tumor response rate (RECIST version 1.1). Furthermore, these variables were also analyzed in relationship to patient progression-free survival (PFS) using Kaplan-Meier methodology and multivariable stepwise Cox regression. Results: Among patients with dMMR mCRC, 29/41 (70.7%) were female, 30 (78.9%) harbored BRAFV600E, and 32 (80%) were sporadic. Median age at start of treatment was 80.6 years (IQR of 75.9, 85.9) and median number of treatment cycles was 9 (IQR: 4, 20). At a median follow-up of 23 months (range, 3.0 to 88.5), patient median PFS was 21.3 months (95% CI: 6.4, 38.5). An overall response was observed in 48.8% (20 of 41) of patients including 13 (31.7%) complete (CR) and 7 (17.1%) partial responses (PR). The median duration of response was 42.2 months (95%CI: 8.6, NR). Patients with metastases that included liver had significantly poorer PFS compared to those with non-liver metastases (HRadj 3.40 (95%CI: 1.27-9.13); Padj= 0. 01). In this regard, responses (CR, PR) to pembrolizumab were observed in 3 (21.4%) patients with liver metastasis compared to 17 (62.9%) of those with non-liver metastases. Treatment-related grade 3 or 4 adverse events were observed in 9 (22.0%) patients of whom two discontinued therapy, and there was one treatment-related death. Conclusions: First-line therapy with pembrolizumab for dMMR mCRC significantly prolonged survival in an elderly patient population with manageable toxicity in routine clinical practice. Moreover, the survival benefit of pembrolizumab was significantly attenuated in patients with liver vs non-liver metastases.
ORIENT-32: Updated characterization of response to sintilimab plus bevacizumab biosimilar (IBI305) vs sorafenib for unresectable hepatocellular carcinoma.
Authors: Ren Zhenggang , Xu Jianming , Bai Yuxian , Xu Aibing , Cang Shundong , Du Chengyou , Liu Baorui , Li Qiu , Lu Yinying , Chen Yajin , Shao Guoliang , Guo Yabing , Chen Zhendong , Fan Jia 
Published: January 2023

570 Background: ORIENT-32 trial (NCT03794440) assessed sintilimab (anti-PD-1 antibody) plus a bevacizumab biosimilar (anti-VEGF antibody) versus sorafenib (Sor) as first-line treatment for unresectable HCC and demonstrated a significant improvement in both overall survival and progression-free survival. Here we report the updated results of objective response rate (ORR), time to response (TTR), duration of response (DoR) and depth of response (DpR). Methods: 571 eligible patients (pts) with unresectable HCC were enrolled and randomized (2:1) to receive sintilimab (200 mg IV Q3W) plus IBI305 (15 mg/kg IV Q3W) or Sor (400 mg orally, BID) until disease progression or unacceptable toxicity. Tumors were evaluated using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)and HCC-modified RECIST (mRECIST). ORR, TTR, DoR, and DpR were analyzed. The DpR was defined as the minimum percentage of (1) sum of longest diameter (SLD) change and (2) longest diameter (LD) change described as mean (standard deviation, SD). Results: At the data cutoff on Dec 30th, 2021, the median follow-up time was 26.7 months. The ORR in sintilimab plus IBI305 and Sor group was 21.0% (77/367) vs 4.7 (8/169) per RECIST 1.1 and 25.1% (92/367) vs 7.7% (13/169) per mRECIST. The median TTR in sintilimab plus IBI305 group was 2.8 (2.4–3.3) months per RECIST 1.1 and 2.6 (1.6–2.9) months per mRECIST. The median DoR in sintilimab plus IBI305gourp was 20.3 (12.3-NE) months per RECIST 1.1. The minimum percentage of SLD change was larger in the sintilimab plus IBI305 arm than in the Sor arm: (−13.4% (35.8) vs 3.2%(26.5) per RECIST 1.1). Similarly, the LD change in the largest liver lesion also favored sintilimab plus IBI305 arm (−27.6% (31.6) vs −11.5% (20.9)), including larger tumors (≥7 cm; −21.2% (30.4) vs −9.9% (23.7)) all per RECIST 1.1. Conclusions: Sintilimab plus IBI305 showed a significant improvement in ORR, TTR, DOR and DpR vs Sor in unresectable HCC. Clinical trial information: NCT03794440 .
Efficacy and safety of TACE combined with anlotinib compared with TACE alone among patients with intermediate or advanced hepatocellular carcinoma (HCC): A randomized, controlled, phase II clinical study.
Authors: Zeng Hui , Shao Guoliang 
Published: January 2023

581 Background: Anlotinib hydrochloride is an oral multi targeted tyrosine kinase inhibitor, mainly targeting VEGFR1-3, FGFR 1-4 and PDGFR α/β. Transcatheter arterial chemoembolization (TACE) is the preferred choice for the treatment of intermediate or advanced HCC. Previous studies have proved that antiangiogenic drugs combined with TACE have synergistic effects. The purpose of this study was to explore the efficacy and safety of TACE combined with anlotinib in the treatment of intermediate or advanced liver cancer compared with TACE alone. Methods: This single-center, randomized controlled, phase II study involved 38 HCC patients with BCLC staging B or C and ECOG PS ≤ 1. Enrolled pts were treated with TACE plus anlotinib (12mg, qd, d1-d14, q3w) and TACE alone until disease progression or unacceptable toxicity. The primary endpoint was progression free survival (PFS), the secondary outcomes included overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Both PFS and tumor response were assessed by investigator per RECIST v1.1. Results: At the cutoff date of April 2022, 18 pts received TACE combined anlotinib and 20 pts received TACE alone. The median PFS was 11.04 months (95%CI, 7.17-14.92) in combination group and 6.87 months (95%CI, 5.58-8.16) in TACE group (HR 0.46, 95% CI 0.23 to 0.92, P=0.022). The median OS has not been reached yet. ORR was 27.8% (95%CI, 9.7%-53.5%) and 30% (95%CI, 11.9%-54.3%) and DCR was 94.4% (95%CI 72.7%-99.9%) and 100% (95%CI 83.2%-100%), respectively, with no statistical difference.The median times of TACE are 2 and 3 respectively.The treatment-related adverse events (TRAEs) of any grade occurred in 15 patients (83.3%) and 19 patients (95%). The most common TRAEs were HFSR (61.1%), hypertension (27.8%), thrombocytopenia (11.1%) in combination group and vomiting (35%), upper abdominal liver pain (35%), upper abdomen pain (30%), low fever (10%), fatigue (10%) in TACE group.Grade ≥ 3 TRAEs occurred in 2 pts (11.1%) in combination group and 1pts (5%) in TACE group. Conclusions: Anlotinib combined with TACE is a safe and effective regimen in the treatment ofpatients with intermediate or advanced-stage hepatocellular carcinoma (HCC). This study still needs longer follow-up to evaluate its efficacy more comprehensively. Clinical trial information: NCT04066543 .