bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real world (RW) use and outcomes of regorafenib (REG) flexible dosing in patients (pts) with metastatic colorectal cancer (mCRC) in Europe.
Authors: Peeters Marc , Chibaudel Benoist , Barzi Afsaneh , Ostojic Helene , Pan Xiaoyun , Yasuda Marie , Chen Chi-Chang , Multani Jasjit , Casey Vicky , Vassilev Zdravko 
Published: January 2024

47 Background: In the phase 2 ReDOS study, REG first-cycle dose-escalation showed comparable activity and lower incidence of adverse events in pts with mCRC vs standard dosing. This retrospective cohort analysis aimed to examine RW dosing patterns of REG and associated duration of treatment (DoT) in pts with mCRC in Europe. Methods: Data from pts with mCRC, aged ≥18 years who initiated REG monotherapy from January 1, 2019 to April 30, 2022, were collected retrospectively from chart review by physicians recruited from the IQVIA OneKey database. Pts were categorized by dosing regimen to either flexible dosing regimens (ReDOS-like [<160 mg starting dose] or dose-adjusted [160 mg starting dose with dose adjustments during treatment]) or a standard dosing regimen (160 mg throughout treatment). Results: Overall, 355 pts (France, n=146; Italy, n=143; Belgium, n=66; 68% male, 54% aged ≥65 years) were eligible for inclusion. Nearly half (49%) received a ReDOS-like regimen, 32% received a standard dosing regimen, and 19% received a dose-adjusted regimen (Table). A higher proportion of pts on a dose-adjusted regimen had ≥3 metastatic sites (64% vs 43% for standard dosing) and most had initiated ≥3 REG cycles (93% vs 67% and 64% for ReDOS-like and standard dosing regimens, respectively). Pts receiving a ReDOS-like dosing regimen had worse performance status (ECOG PS ≥2, 35% vs 30% for dose-adjusted and standard dosing) and a higher proportion of KRAS (42% vs 37% and 30% for dose-adjusted and standard dosing regimens, respectively) or NRAS (28% vs 24% and 21% for dose-adjusted and standard dosing regimens, respectively) mutations. Median DoT was longer for ReDOS-like and dose-adjusted regimens vs standard dosing (1.4 and 1.9 vs 1.0 months, respectively; Table). Conclusions: Pts receiving REG flexible dosing regimens (ReDOS-like, dose-adjusted) had longer DoT compared with a standard dosing regimen despite having a higher frequency of adverse prognostic factors. Thus, this study affirms that flexible dosing strategies are viable options for optimizing REG treatment and outcomes in pts with mCRC. [Table: see text]
Continuation rather than early induction in S-1 adjuvant chemotherapy and prognosis in patients after biliary tract cancer resection.
Authors: Hayashida Kotaro , Adachi Tomohiko , Imamura Hajime , Yamashita Manpei , Tetsuo Hanako , Matsushima Hajime , Hara Takanobu , Soyama Akihiko , Kanetaka Kengo , Eguchi Susumu 
Published: January 2024

474 Background: The efficacy of S-1 monotherapy as adjuvant chemotherapy (AC) for pancreatic cancer has been demonstrated, and the long-term results are clearly improving.1 In biliary tract cancer, the JCOG1201 trial in Japan also demonstrated the usefulness of S-1 AC recently.2 We have been also performed S-1 AC for biliary tract cancer in recent years in accordance with the clinical necessity. In this article, we herein retrospectively analyze the S-1 AC for biliary tract cancer especially in the significance of initiation day or therapy continuation. Methods: 134 patients with the resection of biliary tract cancer (intrahepatic cholangiocarcinoma 25/ hilar 17/ gallbladder 27/ distal bile duct 38/ papillary 25 from January 2017 to December 2021 were included in this study. Age 73(30-87) years, 47 hepatic resections/66 pancreatecticoduodenectomies/21 peri-gallbladder resection. The decision to administer AC was made at the discretion of the attending doctor and in consultation with the patient, and the decision to discontinue was based on the patient's physical condition. If there was no particular need to discontinue, the treatment was continued for six months at least. Results: S-1 AC was performed in 57/137 (43%) of eligible patients. Age was similar between with or without AC patients (73 vs. 73 years old). There were no significant differences by the cancer location. Although pathological stage was higher in the patients with AC (stage 0:1:2:3:4 = 0: 20: 39: 31: 9%) than without AC ( = 9: 45: 33: 10: 3%) (p < 0.001), 2 years recurrence free survival (2y- RFS) was similar between with AC or without AC patients (66.6 vs 71.6%, p=0.82). In the subgroup analysis of the patients with AC, although comparisons of induction day of AC within or after postoperative 6 weeks showed no difference in patient’s prognosis, patients with continuation of AC for at least 6 months after initiation clearly had a better prognosis than without it (2y-RFS: 89.6 vs 41.7%, p=0.003). Conclusions: In S-1 AC for the patients after biliary tract cancer resection, early induction does not play much role, but continuation is important to maintain better prognosis. 1. Uesaka et al. Lancet, 2016. 2. Nakachi et al. Lancet, 2023.
A single-arm, multi-center phase II study of tislelizumab combined with lenvatinib and GEMOX as conversion therapy in potentially resectable locally advanced biliary tract cancer (ZSAB-TransGOLP): A primary analysis.
Authors: Fan Jia , Zhou Jian , Shi Guoming , Huang Xiaoyong , Gao Qiang , Li Xiaowu , Ji Yuan , Liang Fei , Chen Yi , Lu Pinxiang , Qiu Shuangjian , Ren Ning , Shen Yinghao , Xu Yongfeng , Ding Zhenbin , Zhu Xiaodong , Sun Huichuan , Shi Yinghong , Wang Xiaoying , Yi Yong 
Published: January 2024

488 Background: We have previously reported that GEMOX combined with lenvatinib and PD-1 antibody (GOLP regimen) showed promising efficacy as first-line treatment for advanced intrahepatic cholangiocarcinoma (iCCA), indicating that GOLP regimen may be an ideal conversion therapy for patients (pts) with potentially resectable advanced biliary tract cancer (BTC). This phase II trial explored the efficacy and safety of GOLP as conversion therapy in potentially resectable and locally advanced BTC. Methods: Patients with potentially resectable locally advanced BTC were enrolled and received tislelizumab (200mg, Q3W) and lenvatinib (8mg, QD) and GEMOX chemotherapy (Q3W) including gemcitabine 1000mg/m2 on day 1, 8 and oxaliplatin 85mg/m2 on day 1. Tumor responses were evaluated every 9 weeks according to RECIST v1.1, and the resectability was simultaneously discussed by MDT. For pts who were eligible for surgery, capecitabine alone was administered as adjuvant therapy after radical surgery. Pts who was not suitable for surgery continued to the original treatment regimen until progression or intolerable toxicity. The primary endpoint was R0 resection rate, and secondary endpoints included ORR, DCR, PFS, OS, CPR, MPR, RFS. Results: From December 2021 to July 2023, 41 pts were enrolled, 21 males and 20 females with a mean age of 57 years. 87.8% pts had iCCA, 7.3% had perihilar bile duct cancer and 4.9% had gallbladder cancer. TNM stage was II, IIIA, IIIB and IIIC for 2.4%, 34.1%, 58.5% and 4.9% of pts respectively. At cut-off date (September 10, 2023), the mean follow-up was 7.7 months, 39 pts completed at least three cycles of conversion therapy and 7 pts still administered with scheduled conversion therapy. The ORR was 43.9% (18/41) and the DCR was 87.8% (36/41). The median duration of therapy before surgery was 2.9 months (95%CI 2.6-4.6), R0 resection rate was 48.8% (20/41), and 2 pts underwent R1 resection. 9.1% (2/22) pts had a pCR and 22.7% (5/22) had an MPR. The most common grade 3/4 treatment-related adverse events (TRAEs) included neutropenia (31.7%), increased GGT (19.5%), leukopenia (12.2%). No grade 5 AEs occurred. Conclusions: This study demonstrates the high effectiveness and manageable safety of GOLP regimen as conversion therapy for potentially resectable locally advanced BTC. Survival data will continue to be followed up. Clinical trial information: NCT05156788 .
Comparison of the treatment effect between lenvatinib and atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in pathologically diagnosed metabolic dysfunction–associated steatotic liver disease.
Authors: Takahashi Hirokazu , Koshiyama Yuichi , Mitsumoto Yasuhide , Kobayashi Takashi , Hayashi Hideki , Arai Taeang , Sawada Koji , Nonaka Michihiro , Nakahara Takashi , Tomita Kengo , Ito Takanori , Notsumata Kazuo , Seko Yuya , Fujii Hideki , Aishima Shinichi , Yoneda Masato , Toyoda Hidenori , Sumida Yoshio , Nakajima Atsushi , Okanoue Takeshi 
Published: January 2024

493 Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the leading etiologies of HCC. Recent evidence indicates that MASLD might affect the response to immune checkpoint inhibitors and multi-receptor tyrosine kinase inhibitors in the treatment for unresectable hepatocellular carcinoma (HCC), yet real-world data with accurate pathological diagnosis of MASLD has not been confirmed. Methods: Patients with unresectable HCC who had been pathologically diagnosed with MASLD by liver biopsy and/or hepatectomy and later received treatment with lenvatinib (LEN) or atezolizumab plus bevacizumab (ATZ/Bev) as first-line systemic treatment for HCC were included. Outcomes of treatment with LEN or ATZ/Bev were compared. Results: A total of 48 patients who received LEN (n=26) and ATZ/Bev (n=22) were included. The mean time from pathological diagnosis to the initiation of treatment was not different (LEN 1,542 days, ATZ/Bev 1,260 days; p=0.48). The degree of steatosis, inflammation, ballooning hepatocytes and fibrosis did not differ between LEN and ATZ/Bev. At the initiation of treatment, BCLC stage, albumin–bilirubin grade, and Child–Pugh grade did not differ between LEN and ATZ/Bev. The overall response rate and disease control rate evaluated with modified RECIST criteria were not different between LEN and ATZ/Bev (26.1% and 77.2% for LEN, and 22.7% and 70.8% for ATZ/Bev). Median progression-free survival (PFS) was not different between LEN and ATZ/Bev (266 days vs 287 days, p=0.278). Median overall survival (OS) of LEN tended to be longer than that of ATZ/Bev (1364 days vs 663 days, p=0.081). The potential advantage of LEN in OS was statistically significant in the patients with Child-Pugh score = 5 (P=0.0443). A total of 17 patients received both LEN and ATZ/Bev treatment and order of the treatment did not associate with PFS and OS. Conclusions: Outcomes of LEN and ATZ/Bev treatment for advanced HCC were not different in pathologically confirmed MASLD. Longer OS of LEN than ATZ/Bev was observed in the patients with relatively better liver function, suggesting that LEN might be a suitable first-line treatment for HCC with compensated liver function in the patients with pathologically confirmed MASLD.
The efficacy of adjuvant chemotherapy after total mesorectal excision with selective lateral pelvic node dissection for lower rectal cancer.
Authors: Kameishi Shin , Yamaguchi Toshifumi , Hamamoto Hiroki , Okemoto Dai , Kadono Toru , Yukami Hiroki , Goto Masahiro , Nishikawa Hiroki 
Published: January 2024

50 Background: The standard strategy for lower rectal cancer (LRC) is neoadjuvant chemoradiotherapy (CRT) plus total mesorectal excision (TME) in Western countries. TME with or without lateral pelvic node dissection (LND) followed by adjuvant chemotherapy is the standard treatment for LRC in Japan. However, the efficacy of adjuvant chemotherapy for LRC after TME without LND remains unclear. The aim of this study was to assess the efficacy of adjuvant chemotherapy for LRC after TME without LND. Methods: We retrospectively reviewed patients who underwent R0 resection by TME without LND and received adjuvant chemotherapy between 2010 and 2020 at our institution. The inclusion criteria were as follows: age ≥ 20 years; histologically confirmed adenocarcinoma; pathological stage III (UICC 8th); lower rectal cancer (Ra/Rb); patients who received adjuvant chemotherapy after R0 resection without LND and no prior treatment before surgery. We evaluated relapse free survival (RFS) and overall survival (OS) in patients with LRC. Prognostic impact of location, adjuvant chemotherapy regimens, T factor, and N factor on RFS was explored by a multivariate analysis. Results: From a total of 197 patients, 117 patients were eligible. Median age was 65 years (range 26–82) and 54 patients (46%) were male. Tumor location was 67 (57%)/50 (43%) for Ra/Rb and pathologic stage was 47(40%) /61(52%)/ 9(8%) for IIIA/IIIB/IIIC. Eighty patients (68%) received fluoropyrimidine monotherapy (single agent) and 37 patients (32%) received oxaliplatin based therapy (doublet) as adjuvant chemotherapy. The 3-year RFS rate and 3-year OS rate were 70.7% (95% CI, 59.0-81.1%) and 94.5% (95% CI, 89.0-98.1%). The 3-year RFS rates according to tumor location (Ra/Rb) and adjuvant chemotherapy regimen (single agent/doublet) were 76.9%/70.7% and 71.8%/68.5%, respectively. The 3-year RFS rates based on pathological stage (IIIA/IIIB/IIIC) were 76.7%/68.4%/64.8%. In a multivariate analysis, T3/4 were identified as an independent poor prognostic factor for RFS (p<0.05). Conclusions: TME without LND followed by adjuvant chemotherapy for patients with LRC demonstrated favorable 3-year RFS rate. adjuvant chemotherapy regimens after TME without LND suggested no additive efficacy of oxaliplatin on RFS.
Initial uptake of durvalumab with or without tremelimumab for advanced hepatocellular carcinoma in routine clinical practice: Preliminary results of the international DT-real study.
Authors: Celsa Ciro , Nishida Naoshi , Arvind Ashwini , Ulahannan Susanna Varkey , Li Michael , Scheiner Bernhard , Fulgenzi Claudia A.M. , D'Alessio Antonio , Manfredi Giulia F , Stefanini Bernardo , Cabibbo Giuseppe , Cortellini Alessio , Pinter Matthias , Kelley Robin Kate , El Tomb Paul Antoine , Singal Amit G. , Kudo Masatoshi , Pinato David James 
Published: January 2024

501 Background: HIMALAYA trial showed that durvalumab plus tremelimumab (Single Tremelimumab Regular Interval Durvalumab; STRIDE) significantly improved overall survival (OS) and that durvalumab (DUR) was non-inferior compared to sorafenib in patients with hepatocellular carcinoma (HCC). However, real world outcomes on this regimen have not been described. Methods: In the context of a prospectively maintained database including 953 patients (pts) with unresectable HCC treated with immunotherapy, we analysed a subgroup of pts treated with STRIDE or DUR across 5 centres in USA, Asia and Europe. We assessed OS, progression-free survival (PFS), objective response rate (ORR) by RECIST 1.1 (per investigator) and treatment-related adverse events (TRAEs) per CTCAE v.5.0. Results: Between February and May 2023, 59 pts initiated treatment with STRIDE or DUR (mean age 67.2 years, male sex 81.4%). 33 pts (55.9%) were treated in first-line (1L) and 26 (44.1%) in second- or further-line (>1L). STRIDE regimen was administered in 24 patients (40.7%): 6 pts in 1L, 18 pts in >1L. Child-Pugh class was A in 32 pts (54.2%), being more common in pts treated with STRIDE than DUR (79.2% vs 37.1%, p=0.003). ECOG-PS was 0 in 35 pts (59.3%) and it was more common in pts treated with STRIDE than DUR (79.2% vs 47.0%, p=0.015). Outcomes are reported in Table. After a median follow-up of 3.2 months (95%CI 2.6-3.8), median OS was not reached and 6-month OS rate was 59.4%. In pts treated with STRIDE, median OS was not reached and 6-month OS rate was 95.8%, while median OS was 4.9 months (95%CI 3.2-4.9) for DUR. Median PFS was 2.5 months (95% CI 1.9-3.8) and ORR (evaluable in 43 pts, 72.9%) was 16.3% (95%CI 6.5-33.5%). Any grade TRAEs and grade 3-4 TRAEs were 42.4% (95%CI 27.4-62.5) and 10.2% (95%CI 3.7-22.1%), respectively. TRAEs requiring systemic corticosteroid therapy occurred in 3 pts (5.1%). Conclusions: Preliminary observational data from DT-real confirm uptake of STRIDE and DUR across various lines of therapy, with encouraging efficacy and safety outcomes in routine practice. [Table: see text]
The interim analysis of a single-arm, open-label, phase II study investigating ALLEN regimen (durvalumab plus albumin paclitaxel and lenvatinib) in patients with unresectable biliary tract cancers (BTCs).
Authors: Li Zhifang , Chen Meixia , Ming Qianyi , Zhang Yan , Feng Kaichao , Mei Qian , Liu Yang , Han Weidong 
Published: January 2024

504 Background: BTCs are a heterogeneous group of malignancies with a poor prognosis. Despite the improved outcome achieved by the addition of the anti-PD-L1 antibody durvalumab to standard chemotherapy, the benefits were modest and cannot satisfy the clinical demands adequately. This study aimed to evaluate the efficacy and safety of the combination therapy of Albumin paclitaxel, Durvalumab and Lenvatinib (ALLEN regimen) in unresectable BTCs. Methods: This single-arm, single-center, open-label, phase I/Ⅱ study enrolled patients with locally advanced or metastatic BTCs. Eligible patients with ECOG score 0-2 were treated with ALLEN regimen. Durvalumab (1000mg IV, q3w) in combination with albumin paclitaxel (180-220 mg/m2 IV q3w) and lenvatinib (8mg PO QD) were given regularly until disease progression. The primary endpoint was objective response rate (ORR) evaluated by investigators according to RECIST 1.1. The secondary endpoints were disease control rate (DCR), progression-free survival (PFS) and treatment-related adverse events (TRAEs). Results: From September 2021 to September 2023, fourteen patients were enrolled including three patients who were failed to prior anti-PD-1 antibody treatment. The median follow-up was 6.8 months (95% CI 1.9, 10.9). The median age of the patients was 59.0 years, and male patients accounted for 35.7%. The ORR and DCR were 35.7% and 100%, respectively. The median PFS was 7.3 months (95% CI 4.9, 8.2). TRAEs of any grade occurred in 13 (92.9%) patients without grade 3 or higher. The most common TRAEs were alopecia (13/14, 92.9%), peripheral sensory neuropathy (10/14, 71.4%), decreased appetite and nausea (9/14, 64.3%), hypertension (6/14, 42.9%), rash (5/14, 35.7%), diarrhoea (4/14, 28.6%), and asthenia (4/14, 28.6%). Conclusions: The ALLEN regimen demonstrated encouraging anti-tumor activity with a tolerable safety profile in unresectable BTCs. The preliminary results were promising, which deserved further investigation in a larger population. Clinical trial information: NCT05327582 .
Evaluating local tumor destruction and wedge or segmental resection in the treatment of fibrolamellar hepatocellular carcinoma: An NCDB analysis.
Authors: Bine Christopher Reese , Braaten Marco , Czaplicki Alec , Nielsen Eric G. , Lee Aron , Silberstein Peter T. 
Published: January 2024

512 Background: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a rare type of hepatic cancer, comprising 1% of all liver malignancies. Patients are often diagnosed in their second or third decade and often have a palpable liver mass. Treatment primarily consists of surgery and transplant, however, standardized protocols have not been well established due to its rarity. For patients who cannot receive a transplant, there are few studies examining and comparing other surgical types. Using the National Cancer Database, we aim to uncover survival and patient characteristic differences between those who receive Local Tumor Destruction vs Wedge or Segmental Resection. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with FL-HCC from 2004 to 2019 using the histology codes 8171 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 29 and statistical significance was set at α = 0.05. Results: Of the 803 patients in the sample,19 patients received Local Tumor Destruction (LTD) and 142 patients received Wedge or Segmental Resection (WSR). The average age of patients receiving LTD was 54 compared to 32 for WSR. WSR patients experienced longer overall survival than LTD (106 vs. 63 months respectively; p<0.05). When controlling for age, year of diagnosis, tumor size, comorbidity score, and surgery type, WSR showed a greater decrease in overall hazard compared to LTD (HR=0.224 vs 0.306; p<0.05). WSR use was highest in healthy patients with no co-morbidities, however, patients were also significantly more likely to have later stage tumors (II, III, and IV vs. stage I; p<0.001). Despite being associated with a lower OS, LTD was utilized more commonly for earlier stage (stage I vs. II, III and IV; p<0.001) and well differentiated tumors (p<0.001). Compared to WSR, it was associated with higher rates of therapy before and after surgery(p<0.05). There were no significant differences in tumor size, income group, adjuvant therapy type, or facility type (p>0.05) between the treatment groups. Conclusions: Receipt of WSR is associated with improved survival compared to LTD. There are distinct demographic groups which may be guiding surgical selection. Further research into this disparity and other surgical types should be examined to create better guidelines for FL-HCC patients.
Real-world treatment patterns and outcomes in patients with mCRC by MMR/MSI status.
Authors: Crossland Victoria , Peng Jianling , Yin Yu , Huang Yu-Chung , Raizer Jeffrey , Parent Alexander A 
Published: January 2024

52 Background: There are limited data on real-world (RW) treatment patterns and outcomes in patients (pts) with metastatic colorectal cancer (mCRC), especially those with deficient mismatch repair (dMMR)/high microsatellite instability (MSI-H) disease, as they progress through lines of therapy. Methods: Data were extracted from the Flatiron Health electronic health record-derived database. Pts aged ≥18 years diagnosed with mCRC and with ≥2 clinical visits between January 01, 2013 and October 31, 2022 were included. Treatment patterns by therapeutic category and specific agent/regimens were explored across 3 time periods anchored to the start date of first line (1L): years <2017, 2017–2019 and ≥2020 for pts both with dMMR/MSI-H and proficient mismatch repair (pMMR)/microsatellite stability (MSS) disease. Analyzed outcomes, by treatment category, included overall survival (OS), time to treatment discontinuation (TTD) and time to next treatment (TTNT). Descriptive statistics and Kaplan–Meier analyses were conducted. Results: A total of 34,853 pts with mCRC were identified; 24,622 pts (70.6%) were tested for MMR or MSI status, of whom 1,594 (6.5%) were dMMR or MSI-H. After applying key eligibility criteria, 938 dMMR/MSI-H and 12,305 pMMR/MSS pts were included. Overall, chemotherapy-based treatment was the most common treatment category given to pts, but the use of immuno-oncology (IO) agents increased over time. In the dMRR/MSI-H cohort, IO was the most commonly used treatment in 1L and 2L after 2020, driven largely by the use of pembrolizumab. The median OS (mOS) from start of 1L, irrespective of treatment type, was 30.30 months (95% confidence interval [CI]: 24.47, 34.41) in the dMMR/MSI-H cohort and 23.78 months (95% CI: 23.32, 24.34) in the pMMR/MSS cohort. For pts with dMMR/MSI-H, those receiving 1L IO had a mOS of 57.60 months (95% CI: 42.43, not reached [NR]). In pts who had IO after 1L-chemotherapy alone or chemotherapy + targeted treatment, mOS was 52.63 months (95% CI: 38.06, NR) and 59.61 months (95% CI: 34.41, NR), respectively. In pMMR/MSS pts, chemotherapy alone or chemotherapy + targeted treatment had the longest OS when received as 1L-therapy, at 23.88 months (95% CI: 22.89, 25.10) and 24.28 months (95% CI: 23.55, 25.10), respectively. The median TTD and TTNT from start date of 1L, irrespective of treatment type, were 4.90 months (95% CI: 4.28, 5.20) and 7.96 months (95% CI: 7.04, 8.78), respectively, in the dMRR/MSI-H cohort, and 5.79 months (95% CI: 5.72, 5.95) and 10.33 months (95% CI: 10.07, 10.59) in the pMMR/MSS cohort. Conclusions: These real-world data from over 10,000 pts with mCRC supplement findings from clinical trials and limited reported RW evidence. While IO demonstrates significant improvement for pts with dMMR/MSI-H, and mOS is similar regardless of whether IO is given in the 1L or later setting, there remains a high unmet need in pMMR/MSS for additional effective treatment options.