bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real-world treatments and outcomes of resected biliary tract cancers in British Columbia, Canada.
Authors: Boutin Mélina , Safro Maria , Yang Jenny , Jafari Helia , Davies Janine Marie , Gill Sharlene 
Published: January 2023

505 Background: Complete resection followed by adjuvant chemotherapy is standard of care for patients with localized cholangiocarcinoma (CC) or gallbladder cancer (GBC) but is not always feasible and recurrence rates remain high. Understanding the exact proportions and reasons for treatment failure is important to design new approaches, data regarding this information remain scarce. Methods: We performed a retrospective population-based review of patients with GBC or CC (intrahepatic (ICC) or extrahepatic (ECC)) resected between 2005-2019 using the BC Cancer provincial database. Chart review was conducted to characterize demographics, treatments and outcomes. Results: 594 patients were identified of whom 416 (70%) had disease recurrence. Baseline characteristics and treatments received are shown in the table. Most GBCs (96%) were diagnosed incidentally. Repeat oncologic resection was performed for 55% of these, the most common reason for not proceeding was interval disease progression between initial cholecystectomy and planned re-resection (24%). Adjuvant chemotherapy was received by 51% of 163 patients after 2017 and consisted of capecitabine (86%), gemcitabine (4%), cisplatin and gemcitabine (5%) or chemoradiation (4%). Common reasons for not receiving adjuvant therapy were post op complications or comorbidities (18 and 24%), progression (17%) and patient’s preference (17%). Of those receiving adjuvant therapy, 31% did not complete all planned cycles due to progression (45%) or intolerance (55%). Median overall survival (OS) after resection was 31.6 and 18.0 months respectively for R0 and R1 resection (HR 0.43, 95% CI 0.35-0.53), 29.4 and 19.0 months with and without reresection for GBC (HR 0.55, 95% CI 0.41-0.73), and 29.4 and 25.9 months with and without adjuvant therapy (HR 0.79, 95% CI 0.61-1.02). Stage, R0 resection, re-resection for GBC and adjuvant chemotherapy remained associated with improved OS in multivariate analysis. Taken together, only 25% of patients in the more contemporary cohort of 2017-2019 had complete (R0) resection and completed adjuvant chemotherapy. Conclusions: Complete resection, including reresection for incidentally diagnosed GBCs, and adjuvant chemotherapy were associated with improved outcomes in this retrospective cohort, yet many patients were not able to complete these treatments. Neoadjuvant strategies may improve treatment delivery and ultimately, outcomes. [Table: see text]
Health-related quality of life in patients with RAS wild-type metastatic colorectal cancer treated with fluorouracil and folinic acid with or without panitumumab as maintenance therapy: An analysis of the Panama trial (AIO KRK0212).
Authors: Ballhausen Alexej , Karthaus Meinolf , Fruehauf Stefan , Graeven Ullrich , Mueller Lothar , Koenig Alexander , Fischer von Weikersthal Ludwig , Sommerhäuser Greta , Alig Annabel Helga Sophie , Goekkurt Eray , Haas Siegfried , Kurreck Annika , Stahler Arndt , Held Swantje , Reinacher-Schick Anke C. , Kasper Stefan , Heinemann Volker , Stintzing Sebastian , Trarbach Tanja , Modest Dominik Paul 
Published: January 2023

51 Background: The PANAMA study demonstrated superior progression-free survival (PFS) with the addition of panitumumab (Pmab) to fluorouracil and folinic acid (FU/FA) as maintenance therapy following first-line induction therapy with FOLFOX/Pmab in patients with RAS wild-type metastatic colorectal cancer. We report health-related quality of life (HRQOL) analyses of the PANAMA study. Methods: HRQOL was assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) at every cycle of therapy until disease progression. All patients who received at least one dose of induction therapy and completed at least one HRQOL assessment were included into the analysis. HRQOL outcomes were mean changes in EORTC QLQ-C30 from baseline (prior to cycle 1 of induction therapy) to each cycle of treatment (both induction and maintenance therapy). The trial is registered with ClinicalTrials.gov (NCT01991873). Results: In total, 349/377 (93%) of the induction and 237/248 pts (96%) of the maintenance group completed at least one HRQOL assessment and were included in the HRQOL analysis population. There were no significant differences in any of the EORTC QLQ-C30 items between both treatment arms before induction therapy and at randomization. From baseline to cycle 6 of induction therapy there was significant improvement in mean EORTC QLQ-C30 global health status (GHS)/QOL, functioning (except for cognitive functioning) and symptom (except for nausea and vomiting, dyspnea, appetite loss, constipation, and financial difficulties) scores in the randomized population. During maintenance therapy, no significant differences between FU/FA plus Pmab and FU/FA alone were observed. In both arms of the trial, GHS/QOL scores were maintained or trended to improve from baseline (start of induction therapy) to cycle 10 of maintenance therapy (FU/FA plus Pmab: mean difference 9.48 [95% CI 1.96-17.00]; p=0.014); FU/FA arm (mean difference 6.52 [95% CI –1.9-14.95]; p=0.128). Conclusions: Using the established EORTC QLQ-C30 assessment, the addition of Pmab to FU/FA as maintenance therapy in patients with RAS wild-type metastatic colorectal cancer did not impair the HRQOL endpoints analyzed compared to FU/FA alone. These results, along with previously reported improvement in PFS, may support clinical decision-making concerning maintenance treatments. Clinical trial information: NCT01991873 .
Etiologies of cirrhosis by ethnicities of patients with hepatocellular carcinoma.
Authors: Chang Jeremy , Ajmera Veeral , Fowler Kathryn J , Burgoyne Adam 
Published: January 2023

515 Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. While there are several factors that can impact patient outcomes, ethnicity remains a major contributor towards disease incidence and the expected clinical course. There are various etiologies that can lead to the development of HCC among different ethnic groups, though further studies are required to identify the most pertinent risk factors in recent years. Methods: This was a single center, retrospective study in HCC patients to identify differences in cirrhosis etiologies based on ethnicity. All patients were diagnosed with HCC between March 2014 and April 2022. Possible causes of cirrhosis included alcohol, hepatitis B virus (HBV), hepatitis C virus (HCV), nonalcoholic fatty liver disease (NAFLD), and other chronic liver disease. Results: A total of 276 patients were included in this study. For ethnic background, there were 97 Latino, 97 White, 50 Asian, 16 Black, and 16 patients of other ethnicities. With regards to significant differences in the etiologies of cirrhosis, 58 patients (59.8%) of White ethnicity were found to have cirrhosis related to HCV compared to 71 patients (39.7%) of all other ethnic groups (p = 0.002). In addition, when comparing Latino to non-Latino patients, there was a greater proportion of patients with cirrhosis due to NAFLD (24.7% vs 10.1%, p = 0.002) and cirrhosis from alcohol consumption (24.7% vs 10.1%, p = 0.002). HBV also varied significantly by ethnicity with 16 Asian patients (32%) found to have HBV cirrhosis compared to 5 patients (2.2%) of other ethnic groups (p <0.001). See table for additional details. Conclusions: Our study demonstrates significant differences in the cirrhosis etiologies of HCC patients depending on ethnicity. With the incidence and mortality rates of HCC continuing to rise worldwide, it is important for clinicians to be aware of these differences so that the appropriate preventative measures can be pursued.[Table: see text]
An observational study of best supportive care with or without oral capecitabine in patients with metastatic gallbladder cancer.
Authors: Kumar Shaleen , Srivastava Abhinav , Kapoor Vishwas , Misra Shagun , Rastogi Neeraj 
Published: January 2023

521 Background: Patients with metastatic (M+) gallbladder cancer (GBC) have a median survival between 3 - 6 months and therefore palliation of symptoms without compromising quality of life (QoL) is the principal goal of treatment. This study aimed to compare overall survival (OS), toxicity and QoL in patients receiving best supportive care (BSC) with or without oral capecitabine (X). Methods: Patients with M+ GBC and a KPS of ≥70 were prospectively assigned to BSC + X - arm A or BSC alone - arm B, based on physician discretion. Arm A received BSC + X @1650 mg/m2 d1-14, repeated every 21 days for a maximum of 6 cycles. BSC measures included pain palliation; ascitic fluid drainage; jaundice mitigation and other palliative measures. Overall survival (OS) was computed by the Kaplan-Meier method from the date of histologic confirmation and compared using log-rank test. Qol was measured using FACT-Hep v4 administered at baseline, 3 and 6 months. Mean differences in scores were compared using Mann Whitney / Independent t-test and the linear mixed effects model was used for longitudinal analysis to determine the impact of treatment and time on QoL. Results: Between December 2020 to April 2022, 64 patients were assigned, 32 to each arm; data analysed August 2022. For the arms A vs B, the mean age (years) ± SD was 53.3±10.3 vs 54.5±10.3, p=0.21; females, 72% vs 73%, p=0.21; KPS 70, 9% vs 44%, p=0.008; pre-treatment biliary drainage, 9% vs 31%, p=0.06. In arm A, 78% and 21% completed 3 and 6 cycles of X. Median survival was 3.6 vs 2.0 mo, p=0.001; 26 and 27 patients succumbed (~83%), and at 6 months the survival probability was 28% vs 0% respectively; vomiting grade 1-2, 50% vs 78%, p=0.02; diarrhoea grade 1-2, 59% vs 9%, p=0.00; hand-foot syndrome – only arm A, grade 1, 2 & 3 were 32%, 6.5% & 3.2% p=0.001. Baseline QoL mean scores (Table) were significantly worse for most domains in arm B. However, there was no difference in the longitudinal QoL scores between the two treatment arms – FACTG total score (arm*time p=0.759). Conclusions: Not withstanding better prognosis patients of M+ GBC receiving X with BSC compared to BSC alone, a 2 month difference in median survival in favour of arm A was associated with worse diarrhoea and hand-foot syndrome and no discernable impact on longitudinal QoL scores between the two treatment arms.[Table: see text]
Benefits of measuring urinary protein/creatinine ratio in lenvatinib treatment for unresectable hepatocellular carcinoma.
Authors: Morishita Koki , Suzuki Hidetaka , Tauchi Junko , Takeno Misaki K , Yamaguchi Shota , Inoue Kanae , Taira Tomonao , Eguchi Hiroki , Okumura Kei , Shibuki Taro , Satake Tomoyuki , Watanabe Kazuo , Imaoka Hiroshi , Sasaki Mitsuhito , Mitsunaga Shuichi , Kawasaki Toshikatsu , Ikeda Masafumi 
Published: January 2023

529 Background: Proteinuria is a well-known lenvatinib (LEN)-associated adverse event. The standard management of proteinuria includes measurement of the urinary protein/creatinine ratio (UPCR) in patients with a qualitative result for proteinuria of ≥1+. Although several studies have shown a good correlation of the UPCR with the qualitative result, it remains unclear how the management of proteinuria by measuring the UPCR might affect the clinical outcomes. This study was aimed at revealing the effect of measuring UPCR on the treatment efficacy and safety in unresectable hepatocellular carcinoma (uHCC) patients receiving LEN. Methods: We retrospectively analyzed the data of uHCC patients who received LEN between March 2018 and February 2022 at National Cancer Center Hospital East. Patients in the UPCR group were monitored by measurement of the UPCR when the qualitative result was ≥2+, while those in the non-UPCR group were not. LEN was withdrawn when the UPCR was ≥3.5 in the UPCR group, and the qualitative result for proteinuria was ≥3+ in the non-UPCR group. Results: A total of 89 patients were included in this study, of which 39 had a qualitative result for proteinuria of ≥2+. Of these 39 patients with proteinuria, 22 were classified into the UPCR group and the remaining into the non-UPCR group. Of the 209 qualitative results of ≥2+ in the UPCR group, 10 (4.8%) corresponded to a UPCR of ≥3.5. The relative dose intensity of LEN during the first 8 weeks was significantly higher in the UPCR group (64.4%) than in the non-UPCR group (52.8 %, p = 0.047). The time to treatment failure was 12.6 months (95% CI, 6.3-16.9) in the UPCR group and 5.5 months (95% CI, 2.1-11.0) in the non-UPCR group (p = 0.125). The rate of change in eGFR from the baseline to the end of treatment was not significantly different between two groups. Conclusions: Measurement of UPCR might contribute to avoiding unnecessary interruption of LEN, because the UPCR values in most patients were below 3.5.
Early tumor shrinkage as a predictor of survival in patients with locally advanced pancreatic cancer treated with modified FOLFIRINOX or gemcitabine plus nab-paclitaxel combination therapy: An exploratory analysis of JCOG1407.
Authors: Tezuka Shun , Ozaka Masato , Furuse Junji , Uemura Kohei , Sano Yusuke , Nakachi Kohei , Imaoka Hiroshi , Unno Michiaki , Shirakawa Hirofumi , Shimizu Satoshi , Kato Naoya , Kojima Yasushi , Sano Keiji , Ueno Makoto 
Published: January 2023

547 Background: Early tumor shrinkage (ETS) has been reported as a prognostic predictor of chemotherapy for colorectal cancer. However, few studies have examined the potential of ETS in chemotherapy for pancreatic cancer. Herein, we evaluated whether ETS could be a prognostic predictor in patients treated with modified FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin) or GnP (gemcitabine plus nab-paclitaxel) for locally advanced pancreatic cancer (LAPC), as an exploratory analysis of JCOG1407, a randomized phase II selection design trial comparing modified FOLFIRINOX and GnP for LAPC. Methods: Of 126 patients enrolled in JCOG1407, 112 with measurable lesions were included in this exploratory analysis. ETS was defined as a ≥ 20% reduction in tumor diameter compared with baseline at the initial imaging assessment 6–10 weeks after initiating chemotherapy. Patients were divided into two cohorts based on their ETS status as described above: the ETS cohort that achieved ETS and the non-ETS cohort that failed to achieve ETS. The impact of ETS on overall survival (OS) was compared using multivariable Cox regression analysis in (ⅰ) the modified FOLFIRINOX group, (ⅱ) the GnP group, and (ⅲ) the overall population. Results: Herein, we included 55 patients in the modified FOLFIRINOX group and 57 in the GnP group. Notably, 14 (25.5%) and 24 (42.1%) patients achieved ETS in the modified FOLFIRINOX and GnP groups, respectively. In the modified FOLFIRINOX group, the median OS in the ETS and non-ETS cohorts was 2.5 and 1.7 years, respectively; the adjusted hazard ratio (HR) of the ETS to the non-ETS cohort for OS was 0.37 (95% confidence interval [CI], 0.15-0.93). In the GnP group, the median OS in the ETS and non-ETS cohorts was 2.0 and 1.7 years, respectively; the adjusted HR of the ETS to the non-ETS cohort for OS was 0.51 (95% CI, 0.26-1.01). In the overall population, the median OS in the ETS and non-ETS cohorts was 2.3 and 1.7 years, respectively; the adjusted HR of the ETS to the non-ETS cohort for OS was 0.45 (95% CI, 0.27-0.75). Conclusions: We noted a trend toward increased survival in patients who achieved ETS, suggesting that ETS may be a prognostic predictor in patients with LAPC treated with modified FOLFIRINOX or GnP.
Adjuvant chemotherapy for resected intrahepatic cholangiocarcinoma confers no survival advantage.
Authors: Sharib Jeremy , Liu Annie , McIntyre Sarah Margaret Helena , Rhodin Kristen Elizabeth , Kemeny Nancy E. , Cercek Andrea , Harding James J. , Abou-Alfa Ghassan K. , Soares Kevin , Wei Alice Chia-chi , Drebin Jeffrey A. , Kingham T. Peter , D'Angelica Michael Ian , Uronis Hope Elizabeth , Strickler John H , Morse Michael , Zani Sabino , Allen Peter J , Jarnagin William R. , Lidsky Michael 
Published: January 2023

560 Background: Randomized data suggest improved survival with adjuvant chemotherapy for biliary tract cancers, but subset analyses of intrahepatic cholangiocarcinoma (ICC) show limited survival benefit. This study uses a large bi-institutional cohort of resected ICC patients to evaluate the impact of adjuvant therapy on recurrence patterns and overall survival (OS) and compares these findings to data from a national cancer registry. Methods: Patients with resected ICC were identified within a bi-institutional cohort (Duke and Memorial Sloan Kettering, 1997-2020) and the National Cancer Database (NCDB, 2010-2018). Patients were stratified by treatment with adjuvant chemotherapy (adj). Site of first recurrence was categorized as local (liver only), regional (liver and perihepatic nodes), nodal (perihepatic nodes only), distant, or mixed (both liver and distant). OS was compared with Kaplan-Meier methods. Results: 367 patients underwent resection for ICC, and 163 (44%) patients received adjuvant therapy. Median follow-up was 33 vs. 44 months (adj vs observation (obs), p=0.15). 263 (72%) patients had recurrent disease, most commonly in the liver (72%). There was no difference in recurrence patterns stratified by treatment with adjuvant chemotherapy (% recurrence, adj vs obs; local: 42 vs 42; regional: 2 vs 2; nodal: 0 vs 3; distant only: 27 vs 26; mixed: 29 vs 27, p=0.5). OS was the same between groups (adj vs obs; 42 vs 49 months, p=0.3) and when stratified by recurrence site (p=0.5). Similarly, in an NCDB cohort of 1,159 ICC patients over the same time period, there was no association between adjuvant therapy and OS (adj vs obs; 49 vs 57 months, p=0.1). Conclusions: In this retrospective dual registry analysis, corroborated by national data, adjuvant chemotherapy was not associated with an improvement in OS in ICC patients subjected to curative intent resection. Further, adjuvant therapy had no impact on the high rate of hepatic recurrence, suggesting that alternative strategies, such as liver directed therapies, are needed to improve recurrence rates and OS.
The impact of peri-operative chemotherapy on the outcomes of patients with non-metastatic cholangiocarcinoma.
Authors: Baidoun Firas , Alhaj Moustafa Muhamad , Abdel-Rahman Omar 
Published: January 2023

563 Background: Cholangiocarcinoma is a rare malignancy with poor prognosis and outcome despite therapy. It accounts for 2.2% of all new cancer cases and 5% of all cancer deaths. Surgical resection is still the main therapeutic approach, whereas the role of peri-operative chemotherapy is debatable. Methods: The National Cancer Database (NCDB) was queried for patients diagnosed with non-metastatic biliary adenocarcinoma at age 18 or older between 2004 and 2019. After excluding patients with unknown timing of surgery and chemotherapy, patients who died within 90 days of the most definitive primary site surgery and patients lost to follow-up, we split the cohort into three groups according to the clinical stage (stage I-III). Then, we evaluated the overall survival (OS) between the different treatment modalities (surgery only, adjuvant chemotherapy and neoadjuvant chemotherapy) in each group. We studied the OS using Kaplan-Meier estimates and multivariate cox regression analyses to evaluate factors associated with OS. Results: A total of 35,260 patients with non-metastatic cholangiocarcinoma were included in the analysis, of which 50.4% were females, 83% Caucasians, 9.5% African Americans. The median age at diagnosis was 70 (range 18-90). 14,757 (41.9%) were stage I, 12,472 (35.4%) stage II and 8,031 (22.8%) stage III. 7,286 (20.7%) had surgical resection only, 8,144 (23.1%) had chemotherapy only, 6,964 (19.7%) had surgical resection with perioperative chemotherapy and 12,866 (36.5%) did not receive any treatment. We compared survival between different treatment modalities based on clinical stage. In stage I, we found patient who were treated with surgery only had better median OS (mOS) compared to adjuvant chemotherapy (65.7 vs 50.4 months, P<0.001) and no statistically significant difference between neoadjuvant chemotherapy and surgery only (mOS 79.8 vs 65.7 months, P=0.63). Whereas in stage II, patients who were treated with adjuvant and neoadjuvant chemotherapy had better mOS compared to those treated with surgery only (33.9 and 40.3 vs 29.9 months with P<0.001 and P=0.005, respectively). Same trend was seen in stage III, patients who were treated with adjuvant and neoadjuvant chemotherapy had better mOS compared to surgery only (22.6 and 41.5 vs 19.5 months, respectively with P<0.001 for all). In multivariate analysis, adjuvant and neoadjuvant chemotherapy did not affect the OS in all stages, except in stage III where neoadjuvant chemotherapy was associated with better OS (HR 0.646 95% CI 0.530-0.786; P<0.001). Conclusions: Adjuvant and neoadjuvant chemotherapy do not seem to have survival benefit in early stage (stage I and II) cholangiocarcinoma. Whereas neoadjuvant chemotherapy tends to improve OS in stage III.
Real-world data in 1000 patients with unresectable hepatocellular carcinoma (HCC) treated with systemic therapy: Patient background in PRISM study.
Authors: Ikeda Masafumi , Itoh Shinji , Tateishi Ryosuke , Yamashita Tatsuya , Okusaka Takuji , Kato Naoya , Furuse Junji , Kudo Masatoshi 
Published: January 2023

566 Background: Systemic therapy is one of the most important treatment modalities for unresectable hepatocellular carcinoma (HCC). At present, six regimens, except durvalumab plus tremelimumab, are reimbursable for the treatment of HCC in Japan. In clinical practice, there are various patient backgrounds and patterns in the treatment sequence of systemic therapy. Therefore, a prospective, observational, large-scale multicenter study of systemic therapy for HCC (PRISM) was conducted to establish real-world evidence from real-world data in Japan. Methods: Patients with histologically or clinically diagnosed HCC, with no prior systemic therapy, with written informed consent were consecutively enrolled into the study. The primary endpoint is overall survival, and the secondary endpoints are the progression-free survival, time-to-treatment failure, grade 3-4 adverse events, and proportion of transition to subsequent treatment; all endpoints are calculated by each regimen/treatment line. The planned sample size is 1,000 patients with an enrollment and follow-up period of 2 years each. Clinical trial registration: UMIN000040488. Results: From August 2020 to July 2022, the enrollment of 1,000 patients was completed in 42 participant hospitals in Japan. As of Sep 2022, the 1000 patients’ background data have been collected. The median age with range was 73 years (30-93). ECOG performance status was 0 in 612 patients (77.9%), and Child-Pugh score was 5 points in 358 (50.2%) and 6 in 226 (31.7%). BCLC stage was B in 277 patients (36.9%) and C in 391 patients (52.1%). 210 patients (26.8 %) and 207 patients (26.4%) had portal vein tumor thrombosis and extrahepatic metastasis, respectively. The median AFP level was 33 ng/mL (range: 1.1- 524878.9). As first-line therapy, atezolizumab plus bevacizumab was selected in 650 (82.5%), lenvatinib in 116 (14.7%), and sorafenib in 15 (1.9%) patients. Conclusions: The analysis of these real-world data of systemic therapy for patients with unresectable HCC could help clarify the treatment outcomes in clinical practice, and is expected to be broadly applicable to real-world evidence in all Japan. Clinical trial information: UMIN000040488 .