bluuebunny/crossref_metadata_2025_split huggingface dataset:
Camrelizumab in combination with TACE for the treatment of unresectable hepatocellular carcinoma (HCC): A multicenter, single-arm, prospective real-world study.
Authors: You Ran , Yin Guowen , Xu Hao , Zhu Xiaoli , Zhang Qingqiao , Wang Qi , Cao Chi , Lu You , Jiang Hao , Liu Jun , Yu Hui , Xu Qingyu 
Published: June 2021

e16114 Background: Transcatheter arterial chemoembolization (TACE) is considered to be the first-line topical therapy for unresectable hepatocellular carcinoma (HCC). However, the long-term efficacy of single TACE treatment is poor, with a five-year survival rate of 8%-43%. This study aims to investigate the efficacy and safety of TACE combined with camrelizumab in the treatment of unresectable HCC. Methods: This is a single-arm, prospective real-word study conducted in 14 hospitals in Jiangsu, China. Patients diagnosed with HCC received Camrelizumab (200mg, i.v. Q2W or Q3W) with or without antiangiogenic therapy (apatinib, lenvatinib, sorafenib, or regorafenib) at any stage of the TACE treatment. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Kaplan-Meier method was used for survival analysis. This study was registered with ChiCTR.org.cn, number ChiCTR1900026163. Results: From September 2019 to January 2021, 151 patients were enrolled, of whom most were males and younger than 65 years, 92 (60.93%) had extrahepatic metastasis and 120 (79.47%) suffered from HBV infection, 59 (39.07%) had an AFP concentration of 400 ng/mL or higher, 150 (99.34) had an ECOG PS of 0 or 1, a Child-Puph score of A or B, and were classified as BCLC Stage B or C. In addition to TACE, 52 patients received camrelizumab alone, while the others also received antiangiogenic therapy. Most (139, 92.06%) of the patients received camrelizumab 200mg every 3 weeks. Of the 112 patients who were available for efficacy evaluation, 4 patients achieved CR, 25 achieved PR, and 53 achieved SD, resulting in an ORR of 25.89% and DCR of 73.21%. The median PFS was 4.27 months (95% CI, 3.45 to 7.36 months) and the median OS was 14.0 months (95% CI, 10.6 to NE months). The safety data were obtained from 140 patients. Treatment-related adverse events (TRAEs) occurred in 130 (92.86%) patients, with the commonest types including increased alanine and aspartate aminotransferases (65%), thrombocytopenia (57.86%), hypoalbuminemia (54.29%), hyperbilirubinemia (48.57%), anemia (42.86%), leukopenia (42.14%), neutropenia (37.14%) and proteinuria (20.71%). Severe AEs occurred in 52 (37.14%) patients, with the commonest types including thrombocytopenia (17.14%), increased alanine and aspartate aminotransferases (13.57%), neutropenia (8.57%) and hyperbilirubinemia (7.14%). Conclusions: The treatment strategy of TACE in combination with camrelizumab with or without antiangiogenic therapy showed encouraging clinical efficacy and manageable toxicity profile in treating unresectable HCC, which provided a new treatment option for HCC. Clinical trial information: ChiCTR1900026163.
Impact of bodyweight (BW)-based starting doses on safety and efficacy of lenvatinib (LEN) in patients (pts) with hepatocellular carcinoma (HCC).
Authors: Okusaka Takuji , Kudo Masatoshi , Ikeda Kenji , Ikeda Masafumi , Okita Kiwamu , Tamai Toshiyuki , Ren Min , Saito Kenichi , Kumada Hiromitsu 
Published: June 2021

e16119 Background: In Study 202, pts received LEN 12 mg/d for treatment of unresectable (u)HCC, irrespective of BW. Correlations between early dose adjustments and BW in Study 202 led to BW-adjusted dosing in the phase 3 REFLECT study of LEN in uHCC. In REFLECT, pts <60 kg received LEN 8 mg/d and pts ≥60 kg received LEN 12 mg/d. While improvements in safety were expected by reducing the LEN starting dose to 8 mg/d in pts <60 kg, any differences in safety and efficacy of BW-adjusted dosing vs standard dosing among pts with lower BW have yet to be determined. Herein, we compare safety and efficacy of LEN based on pts’ BW (<60 kg vs ≥60 kg) in Study 202 (LEN 12 mg/d irrespective of BW) and in Japanese pts in REFLECT (dose adjusted by BW). Methods: This ad hoc analysis included all pts from Study 202 (n=46; all Asian, 43 Japanese) and Japanese pts from REFLECT (n=81). Safety and efficacy were assessed in Study 202 and REFLECT according to pt BW (<60 kg vs ≥60 kg). Tumors were assessed using mRECIST, by independent radiologic review. Results: In Study 202, pts in the <60 kg group had a median treatment duration of 5.8 mos and received 57% of the LEN planned starting dose (PSD); pts in the ≥60 kg group had a median treatment duration of 9.4 mos and received 78.6% of the LEN PSD. Among Japanese pts in REFLECT, median treatment duration was 5.7 mos in both treatment groups; pts in the LEN 8 mg group received 79.1% of the PSD and pts in the LEN 12 mg group received 70.7% of the PSD. In Study 202, treatment-related adverse events (TRAEs) led to dose reduction in 80.8% of pts in the <60 kg group and 55% of pts in the ≥60 kg group. In REFLECT, TRAEs led to dose reductions in 52.5% of pts in the LEN 8 mg group and 70.7% of pts in the LEN 12 mg group. Serious TRAEs occurred at incidences of 46.2% and 10.0% in Study 202 in the <60 kg and ≥60 kg groups, and 15.0% and 22.0% in REFLECT in the LEN 8 mg and LEN 12 mg groups, respectively. Efficacy results are in the Table. Conclusions: Despite the small sample size, this comparison of Study 202 pts and Japanese pts from REFLECT indicates that BW-adjusted LEN dosing in pts with uHCC yielded comparable efficacy between pts <60 kg who received LEN 8 mg and pts ≥60 kg who received LEN 12 mg. The safety profile was favorable in pts <60 kg who received LEN 8 mg in REFLECT vs those who received LEN 12 mg in Study 202. Fewer serious TRAEs and dose reductions due to TRAEs were observed in pts with lower BW who received the LEN 8 mg starting dose in REFLECT. These data suggest that by reducing the starting dose from LEN 12 mg to 8 mg in pts with uHCC and lower BW (<60 kg), safety is improved without compromising efficacy. Clinical trial information: NCT00946153; NCT01761266. [Table: see text]
A pilot study of the combination of checkpoint inhibition with ablation in subjects with biliary tract cancer.
Authors: Wetzel Rebecca , Monge B. M. Cecilia , Xie Changqing , Mabry-Hrones Donna , Webb Santhana , Akoth Elizabeth , Redd Bernadette , Levy Elliot B , Wood Bradford , Greten Tim F. 
Published: June 2021

e16150 Background: Immune checkpoint inhibition has demonstrated modest activity in biliary tract carcinoma (BTC). Augmentation of the immune response by ablative procedures to improve efficacy of immune checkpoint inhibition has been previously demonstrated in hepatocellular carcinoma, however the outcome of the combination of immune checkpoint inhibition with tremelimumab (anti-CTLA4) and durvalumab (anti-PD1) with ablation in advanced biliary tract carcinoma is unclear. The primary objective of this study was to establish the efficacy via 6-month progression-free survival (PFS) of combining tremelimumab and durvalumab in patients with advanced BTC either alone or with tumor ablation. Secondary objectives were safety and feasibility of combination treatment. An exploratory objective was overall survival (OS). Methods: Eligible patients had histologically confirmed advanced or unresectable BTC (intra- or extrahepatic cholangiocarcinoma, gallbladder cancer, or ampullary cancer) who had progressed on, been intolerant to, or refused prior chemotherapy. Disease had to be technically amenable to cryoablation with at least two measurable lesions. Adequate organ function and an ECOG of 0 or 1 were required. Patients were treated with tremelimumab and durvalumab with or without tumor ablation. Tremelimumab and durvalumab were administered intravenously every 28 days for four cycles followed by durvalumab every 28 days until disease progression. Cryoablation was performed on day 36. Patients were imaged every 8 weeks and response was defined per RECIST v 1.1 criteria. Results: In total, 22 patients have been enrolled into the BTC cohort. Half underwent ablation and half received immunotherapy alone. The median age was 59 years (range 21-80). All patients had received prior systemic chemotherapy, locally advanced disease was present in 68% of patients. Median PFS was 2.1m and median OS was 5.6 m. DCR was 45% (SD). Median OS and PFS was similar in the group that received ablation vs immunotherapy alone with a median OS of 6.8 m vs 6.7 m and 2.0 m vs 2.7 m respectively. The most common grade 3- 4 adverse events were lymphopenia (27%), increased AST (41%), increased alkaline phosphatase (32%) and elevated bilirubin (27%). Conclusions: Combination checkpoint inhibition combined with tumor ablative procedures is a safe and effective treatment strategy for patients with advanced BTC, however the addition of ablative therapy may not enhance efficacy in this small cohort of patients. Results illustrate the poor prognosis of advanced BTC and may represent a non-chemotherapeutic approach to treatment in this patient population. Further studies are warranted to identify patient populations most likely to respond to these interventions. Clinical trial information: NCT02821754.
Analysis of DNA damage repair pathway genes as a predictive biomarker for HAIC in hepatocellular carcinoma.
Authors: Mai Qicong , Mo Zhiqiang , He Jian , Chen Tingting , Huang Mengli , Chen Xiaoming 
Published: June 2021

e16159 Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide.Hepatic arterial infusion chemotherapy (HAIC) with oxaliplatin, fluorouracil, and leucovorin (FOLFOX) is one of the effective treatment for advanced HCC patients. DNA damage repaired (DDR) pathway has been widely researched in many cancers recent years, which was a promising predictive biomarker for the response to platinum-based chemotherapy and Immunotherapy. But the DDR characteristics of different subset pathways in HCC, and its correlation with HAIC efficacy were unknown. Methods: Whole exome sequencing (WES) data of 366 HCC patients was obtained from the Cancer Genome Altas (TCGA). Next generation sequencing (NGS, panel on 381/733-gene) was performed on FFPE tumor samples from 2092 Chinese HCC patients (Chinese cohort). Germ-line or somatic mutations of 32 DDR pathway genes (including Mismatch Repair and Homologous Recombination) were classified as DDR gene mutations. TMB was defined as total number of somatic non-synonymous mutations in coding region. Whole exome sequencing (WES) data and clinical data of 21 HCC advanced patients treated with HAIC were obtained to survival analysis. Results: In total, 59.84% (219/366) of HCC patients in TCGA harboring DDR mutation and 67.38% (1316/2092) in Chinese cohort. In Chinese HCC cohort, the mean TMB level of DDR mutant group was significant higher than wild-type group (mean TMB, mutation vs wild-type = 8.12 vs 6.42 Muts/Mb, P < 0.0001). The top three mutation frequency DDR genes were BRCA2 (17%), ATM (13%) and BARD1 (12%), respectively. The highest mutation frequency DDR subset pathways were Fanconi anemia (FA, 44.14%, 862/2092), homologous recombination repair (HRR, 38.71%, 756/2092) and check point factors (CHP, 17.31%, 338/2092) come in second and third, respectively. Next we compared the TMB level between different DDR subset pathways, the mutant of nucleotide excision repair (NER) pathway harbored the highest medium TMB level (7.26 Muts/Mb). The survival analysis was performed on HCC patients treated with HAIC with FOLFOX. There was no difference in clinical baseline information between DDR mutation group (n = 6) and wild-type group (n = 15). The progression-free survival (PFS) of DDR mutation group were significantly longer than wild-type group (median PFS, mutation vs. wild-type = 8.9 vs. 4.5 months; HR 0.34[95% CI 0.13-0.85]; P = 0.0349), and an extending trend on overall survival (OS) without significant difference (median OS, 15.7 vs 8.9 months; HR 0.37[95% CI 0.13-1.00]; P = 0.0921). Conclusions: The DDR pathways was associated with higher TMB level. Preliminary data from clinical cohorts suggested better treatment outcomes of HAIC with FOLFOX in DDR mutation HCC patients.
A phase Ⅰ open-label dose-escalation study of AL2846 in combination with gemcitabine in patients with locally advanced or metastatic pancreatic adenocarcinoma.
Authors: Liu Rui , Deng Ting , Bai Ming , Zhang Le , Ning Tao , Wang Xia , Ji Zhi , Yang Yuchong , Ge Shaohua , Li Hongli , Duan Jingjing , Ba Yi 
Published: June 2021

e16210 Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a 5-year survival rate of 10%. Overexpression of c-Met is associated with the poor prognosis in patients with PDAC and it was noted that phosphorylation of c-Met is increased in gemcitabine-resistant PDAC. AL2846 is an oral c-Met inhibitor, which targets multiple receptor tyrosine kinases (RTK’s) primarily including c-Met, VEGFR1, KIT, Axl and RET. The combination of AL2846 with chemotherapy may improve the clinical efficacy of PDAC. Based on these consideration, a phase Ⅰ clinical trial was initiated to determine the maximum tolerated dose (MTD) of AL2846 in combination with gemcitabine in patients with advanced PDAC and to clarify the potential anti-tumor activity. Methods: Patients with untreated locally advanced or metastatic PDAC were enrolled to receive oral AL2846 once daily in a fasted state in combination with gemcitabine intravenous infusion over 30 min on days 1, 8, and 15 every 28 days. The starting dose level is AL2846 40 mg and gemcitabine 1000 mg/m2. Primary endpoint was the maximum tolerated dose (MTD), defined as the highest dose level at which ≤33 % of patients incurred a dose-limiting toxicity (DLT), and RP2D. Secondary endpoints included response rate (ORR), progression-free survival (PFS) and overall survival (OS). Results: As of January 1, 2021, a total of 15 patients with PDAC were enrolled and received 4 dose-levels of AL2846 (40 mg: n = 1; 60 mg: n = 6; 90 mg: n = 3; 120 mg: n = 5) treatment. DLTs occurred in 1 patient who experienced grade 3 abnormal liver function. The most common grade 3 or above drug-related adverse events were neutropenia (n = 7, 46.7%), thrombocytopenia (n = 5, 33.3%), leukopenia (n = 4, 26.7%), GGT increased (n = 4, 26.7%), hyperbilirubinemia (n = 3, 20.0%) and alkaline phosphatase increased (n = 3, 20.0%). Among the 15 patients available for efficacy evaluation, 1 patient (6.6%) achieved partial response who was at the dose levels of 90mg. There were 4 patients whose PFS was more than 5 months. Although there were no more than 2 DLT events, we chose 90 and 120 mg as the target dose for RP2D according to the dose reduction and proportion of gemcitabine. Conclusions: The RP2D of AL2846 in combination with standard dose of gemcitabine were 90 and 120 mg QD continuously. The results demonstrated that AL2846 in combination with gemcitabine was well tolerated at doses up to 120 mg. Further clinical studies about the efficacy of AL2846 in pancreatic cancer are in progress. Clinical trial information: CTR20201021.
Association of TP53 mutation status and GATA6 amplification with clinical outcome of pancreatic cancer.
Authors: Yang Jung-In , Ha Taehoon , Zhou Edward , Tzanavaris Chris , Devoe Craig E. , Zhu Xinhua , Boyd Jeff 
Published: June 2021

e16224 Background: Recent advances in pancreatic adenocarcinoma (PDAC) research unveiled that molecular subtypes reflect cancer prognosis and chemosensitivity. Here, we examined the possible use of genomic profiling of PDAC in the clinic by assessing retrospective clinical outcomes and treatment responsiveness based on genetic alterations. Methods: All patients treated for PDAC with Next-Generation Sequencing (NGS) data available between 2014 to 2020 at Northwell Health Cancer Institute were included in a retrospective analysis. Patients were subdivided into resectable and unresectable cancer. Genetic findings frequently reported in NGS were used to compare progression-free survival (PFS) and overall survival (OS) within subgroups. Survival probability was compared using Peto-Peto’s modified survival estimate followed by pairwise comparisons using Peto-Peto’s modified survival estimate. Family-wise error rate was adjusted using Benjamini & Hochberg method. Results: A total 115 patients were qualified for the evaluation. In all cases of PDAC, TP53 mutation (n = 89) was associated with poor OS compared to the wild-type TP53 gene (n = 19) (median OS 20.2 months, 95% CI 10.2 to 39.7, vs. 41.1 months, 95% CI 20.9 to 81.0, HR 1.98, p = 0.028). In unresectable PDAC, tumors with GATA6 amplification (n = 11) were associated with a significantly better OS over patients whose tumors harbored a TP53 mutation (n = 57) (median OS 22.9 months, 95% CI 9.6 to 54.5, vs. 10.0 months, 95% CI 4.2 to 23.8, HR 0.48, p = 0.048) . Within the TP53 mutation group, FOLFIRINOX (n = 21) did not show improved OS compare to Gem/NabP (n = 30) (mean OS 13.8 months, 95% CI 6.8 to 28.2, vs. 8.5 months, 95% CI 4.17 to 17.4, HR 0.84, p = 0.25). Other genetic alterations were not associated with OS. There was no difference in PFS in all PDACs. Conclusions: Our retrospective analysis showed that genetic changes in TP53 and GATA6 were significantly associated with the clinical outcome for PDAC. Mutation of TP53 was associated with poor OS in general. However, in unresectable PDAC, GATA6 amplification was associated with better clinical outcome than tumors with TP53 mutation. In contrary to general belief, FOLFIRINOX did not result in better OS than Gem/NabP.
The impact of first-line chemotherapy in elderly patients (pts) with advanced pancreatic cancer (APC): A mono-institutional retrospective study.
Authors: Chiaravalli Marta , Maratta Maria Grazia , Bensi Maria , Di Stefano Brunella , Ribelli Marta , Barone Diletta , Gurreri Enrico , Monaca Federico , Cutigni Claudia , Bagalà Cinzia , Tortora Giampaolo , Salvatore Lisa 
Published: June 2021

e16229 Background: Pancreatic cancer median age at diagnosis is 70 years old. However, elderly pts are underrepresented in randomized clinical trials (RCTs) and chemotherapy efficacy and safety data in this population are limited. Herein, we present a retrospective analysis of an elderly population treated at our Institution, investigating the role of baseline clinical factors in guiding treatment decision making. Methods: Pts aged ≥70 years old receiving a first-line chemotherapy for APC were included in the analysis. The primary end-points were progression-free survival (PFS) and overall survival (OS). The following variables were collected: gender; age (≥ 70 and < 75 years vs ≥ 75 years); baseline ECOG PS (0-1 vs 2-3); site of primary tumor (head/uncinate process vs body/tail); disease stage (locally advanced vs metastatic); baseline CA 19.9 ( < vs ≥ 200); chemotherapy regimen; comorbidities (yes vs no); number of comorbidities (0-1 vs ≥ 2). Univariate and multivariate analysis for PFS and OS were performed. Results: A total of 169 APC pts aged ≥70 years old, receiving first-line chemotherapy between March 2015 and August 2020, were included in the analysis. The median age was 76 years (70-89), ECOG PS was 0-1 in 77% of pts; 70% were metastatic; 70% of pts had a head/uncinate process primary tumor; 25% had baseline CA 19.9 ≥ 200; 9.4% of pts had no comorbidities and 50% had ≥2 comorbidities. The majority of pts received gemcitabine nab-paclitaxel (60%), other regimes included gemcitabine (28%), FOLFIRINOX (5%), capecitabine (4%), FOLFOX (2%) and FOLFIRI (1%). The overall population median PFS and OS were 6.5 (median follow-up 19.1 months) and 11 months (median follow-up 21.8 months), respectively. Out of 164 pts evaluable, 38 (23%) pts achieved a partial response and 58 (35%) a stable disease, with a disease control rate of 58%. At the multivariate analysis, ECOG PS 0-1 resulted independently associated both with improved PFS (p 0.005) and OS (p 0.0084). At the multivariate analysis for PFS, also locally advanced stage resulted significantly associated with better PFS (p = 0.036). In pts with ECOG PS 0-1 vs 3-4 the median PFS was 6.7 vs 3.3 months (p 0.0004) and median OS was 11.3 vs 5.5 moths (p 0.003), respectively. Conclusions: Despite the retrospective nature of the analysis and the limited sample size, we observed that elderly APC pts can benefit from a first-line treatment achieving survival outcomes comparable to the one reported for younger pts in RCTs. On the basis of our results, the baseline ECOG PS can be considered a prognostic factor for both PFS and OS. In conclusion, elderly pts should not be precluded from an active treatment and careful patient selection, mainly according to baseline ECOG PS, should guide treatment indication.
Patient's characteristics and outcome of small bowel adenocarcinoma in Saudi Arabia.
Authors: Alshamsan Bader I , Badran Ahmed ali , Aseafan Mohamed , Shaheen Amgad , Elshenawy Mahmoud Abdelsatar , Aljubran Ali H 
Published: June 2021

e16277 Background: Small bowel adenocarcinoma (SBA) is a rare disease. We aim to describe patient's characteristics and clinical outcomes among Saudi patients. Methods: All patients with SBA diagnosed between 2007 - 2020 were reviewed. Logistic regression was used to assess variables associated with metastasis at diagnosis, and a log-rank test was used to compare factors associated with survival. Results: Forty-three patients were eligible for analysis, and (76.7%) were males. The median age at diagnosis was 53 years. History was significant for colon cancer in two patients, celiac disease in three patients, Lynch syndrome, Familial adenomatous polyposis (FAP), Non-APC in one patient, and cholecystectomy in seven patients. The common initial presenting symptoms were abdominal pain (58.8%), bowel obstruction (30.2%), Overt gastrointestinal bleeding (9.3%). Tumor markers were elevated in 21 patients. EGD was used for diagnosis in 60.5%, while CT scan in 23.3%. The most common primary site was duodenum 60.5%, jejunum 27.9%, ilium 7%. Stage IV was (41.9%). The most common site for metastases was the liver in 10 patients. Patients' ECOG performance status was 0/1 in 51% at diagnosis. Univariate analysis did not reveal that patients with high Neutrophil-lymphocyte Ratio (NLR) (≥0.85) are more likely to be metastatic; P = 009. There was no association of sex, presenting complaints, tumor markers with the stage at diagnosis. Surgery was performed for 53.4% of patients (RO, 73%), and the median DFS was 49 vs. 8 months in R0 vs. R1 group, respectively (p = 0.01). FOLFOX Chemotherapy regimen was given for 10 patients as adjuvant treatment and for 8 patients for metastatic sitting. The median duration of follow-up was 12 months. The median overall survival (OS) for localized stages was not reached, and for the metastatic stage was 10 months. The 3 years OS based on stages were 100% (I), 85% (II), 53% (III) and 35% for (IV), p = 0.001. Other factors associated with survival were ECOG Performance status (p < 0.001), NLR ( < 0.001), CA19-9 (p = 0.04), and receiving chemotherapy in a metastatic setting (p = 0.02). Conclusions: SBA is diagnosed at a younger age in Saudi patients and more in males. The advanced stage, lower performance status score, high CA19-9, and high NLR at diagnosis are associated with poor OS. NLR could be a prognostic factor for a metastatic stage at diagnosis.