bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatocellular carcinoma and liver metastasis treated by hafnium oxide nanoparticles activated by SBRT: A phase I/II trial.
Authors: Chajon Enrique , Pracht Marc , De Baere Thierry , Nguyen France , Bronowicki Jean-Pierre , Vendrely Veronique , Baumann Anne-Sophie , Valérie Laurent , Rio Emmanuel , Rolland Yan , Le Sourd Samuel , Gustin Pierre , Perret Christophe , Mornex Francoise , Peiffert Didier , Merle Philippe , Deutsch Eric 
Published: January 2019

340 Background: Hafnium oxide nanoparticles, NBXTR3, were developed to increase the tumor-localized high energy deposit once activated by ionizing radiation such as stereotactic body radiotherapy (SBRT) and thus to increase tumor cell death compared to the same dose of radiation. NBTXR3 is characterized by a single intratumor/intralesional (IL) administration and fits into standard RT schedule with no change in patient’s flow, treatment protocol or equipment. Herein the preliminary results of a phase I/II clinical trial evaluating this combination in patients (pts) with hepatocellular carcinoma (HCC) or liver metastasis (mets). Methods: HCC and liver mets patients were treated with an IL injection of NBTXR3 followed by SBRT (15 Gy∗3 fractions). The phase I part of the trial follows a 3+3 dose escalation design at dose levels of NBTXR3 corresponding to 10%, 15%, 22%, 33% of the baseline tumor volume. This study aims primarily to identify the Recommended Dose and the incidence of early Dose Limiting Toxicities (DLTs) of NBTXR3 activated by SBRT. Secondary endpoints include assessment of global safety profile, liver function evaluated by Child-Pugh score (CPS), AST to Platelet Ratio Index (APRI), and response rate (mRECIST/RECIST 1.1). Results: Enrollment is at the last dose level, 33%, and completed at 10% (6 pts), 15% (4 pts) and 22% (4 pts). So far, no early DLTs nor severe adverse events related to NBTXR3 were observed. Both CPS and APRI did not reveal important variations in accordance to NBTXR3 low toxicity. The best observed target lesions responses, among 7 evaluable HCC pts for response (mRECIST), were: 3 complete responses, 3 partial responses (PR) and 1 stable disease (SD) and among 5 evaluable liver mets pts: 1 PR, 3 SD and 1 progressive disease (RECIST 1.1). Conclusions: NBTXR3 is well tolerated at the 22% dose level with an overall positive safety profile. This innovative approach might constitute a valuable solution for pts with liver tumors beyond standard treatment lines. NBTXR3 was successful in a phase II/III in soft tissue sarcoma [NCT02379845] and is currently evaluated in head and neck [NCT01946867; NCT02901483], prostate [NCT02805894] and rectum cancers. Clinical trial information: NCT02721056.
Risk factors of hepatic failure after liver resection for perihilar cholangiocarcinoma: Importance of future liver remnant volume, body weight ratio, and impact on long-term survival.
Authors: Lee Jong Woo , Lee Jae Hoon 
Published: January 2019

348 Background: Hepatic resection for perihilar cholangiocarcinoma (PHCC) is associated with high postoperative mortality. Future liver remnant volume to total liver volume ratio has been used to anticipate the risks associated with liver resection for PHCC. We sought to investigate the independent factors associated with postoperative hepatic failure (PHLF) and assess predictive value of future liver remnant volume – body weight (FLRV/Wt) ratio after resection for PHCC. Methods: This study included 287 patients who underwent major hepatectomy including caudate lobectomy with bile duct resection for PHCC between 2008 and 2015 in single center. FLRV were calculated with CT volumetry and perioperative clinical and operative data were analyzed to identify independent determinants of PHLF (grade B/C according to the International Study Group of Liver Surgery criteria) and major postoperative complications (Dindo III to IV). Results: Combined Portal vein resection was performed in 18.8%. PHLF incidence was 13.6% and 90-day mortality was 3.5%. On multivariate analysis, predictors of PHLF (p < 0.05) were FLRV/Wt ratio < 0.5 (odds ratio [OR] 9.45), ICG R15 > 15 (OR 3.72), BMI < 25.0 (OR 6.41) and R1 resection (OR 3.97). There was no significant difference of survival between two groups divided by FLRV/Wt ratio (0.5) in Kaplan-Meier analysis. There was significant difference of survival according to PHLF. In without PHLF group, 1yr, 3yr, 5yr survival were 83.1%, 45.2%, 28.1%. In PHLF B group, 1yr, 3yr, 5yr survival were 66.7%, 40.7%, 20.7% respectively. Conclusions: Insufficient FLR volume (FLRV/Wt < 0.5), ICG R15 (< 15), BMI (< 25) and R1 resection is associated with PHLF for patients with PHCC. We confirmed that PHLF is also associated with long term outcome. Preoperative assessment to patients with PHCC should be optimized to minimize the risk of PHLF. [Table: see text]
Early stage hepatocellular carcinoma treated with stereotactic body radiation therapy: A pooled analysis from two North American institutions.
Authors: Mathew Ashwathy Susan , Atenafu Eshetu G. , Owen Dawn , Maurino Chris , Brade Anthony M. , Brierley James D. , Dinniwell Robert Edward , Kim John , Cho Charles , Ringash Jolie , Wong Rebecca , Cuneo Kyle Clifford , Feng Mary Uan-Sian , Lawrence Theodore Steven , Dawson Laura A. 
Published: January 2019

350 Background: To report outcomes of pooled data from patients with early stage hepatocellular carcinoma (HCC) treated with stereotactic body radiation therapy (SBRT) at two North American Institutions. Methods: An IRB approved collaborative review of patients with HCC treated with radical intent SBRT was conducted. Inclusion criteria included patients with Stage I-IIIA HCC (UICC/AJCC 7th Ed.) treated with SBRT (≥ 4.5 Gy/ fraction) from June 2003 until Dec 2016. Patients who were treated with SBRT were ineligible for resection, percutaneous ablative or hepatic intravascular therapies. Patients with vascular invasion and those treated with palliative intent (e.g. HCC rupture) were excluded. Overall survival, local control and toxicity of treatment were reviewed retrospectively. Results: Of 310 eligible patients, 23% were Child-Pugh (CP) class B/C (21%/2%), and 40% had failed prior liver directed therapies. The median HCC diameter was 2.4 cm (range 0.5-18.1 cm), and the median prescribed dose was 39 Gray (Gy) in 5 fractions (range: 14 - 60 Gy in 2-6 fractions). Median BED was 78.75 Gy (Range: 23.8-180.0 Gy). 8.4% of patients underwent liver transplant after SBRT. Local control at 1, 3 and 5 years was 91.5%, 82.6% and 82.6%. On multivariable analysis (MVA), the use of breath-hold motion management, but not T stage, size or dose, was significantly associated with local control (p = 0.0098). The 1, 3, and 5 year overall survival (OS) was 77.3%, 37.9% and 23.5%. Factors associated with improved OS on MVA included baseline CP A score (HR = 0.58, p < 0.0045), AFP < 10 µg/L (HR = 0.66, p = 0.0094), and transplant post SBRT (HR = 0.05, p < 0.0001). The median survival of CP A vs. B/C patients was 30.3 and 17.6 months respectively. CTCAE (v4.0) grade 3 or higher luminal gastrointestinal organ toxicity occurred in 2.5% of patients, while a decline in CP score ≥ 2 points was seen in 16.7% of patients at 3 months post SBRT. Grade 3 and above elevated liver enzymes were seen in 12.6% and 8.1% of patients at baseline and at 3 months post SBRT. Conclusions: Similar to Asian series, this North American pooled analysis found high sustained local control and excellent survival in patients with early stage HCC treated with SBRT.
Survival and cost associated with chemotherapy and chemoradiotherapy among resected pancreas cancer patients.
Authors: Vela Nivethan , Davis Laura , Cheng Stephanie Y , Hammad Ahmed , Liu Ying , Kagedan Daniel , Bubis Lev , Earle Craig , Paszat Lawrence Frank , Myrehaug Sten , Mahar Alyson L. , Mittmann Nicole , Coburn Natalie G. 
Published: January 2019

351 Background: Pancreas cancer is expensive to treat, and the effectiveness of adjuvant chemotherapy (CT) and chemoradiation (CRT) following resection is debated. We compared both survival and healthcare costs by adjuvant therapy after curative-intent pancreaticoduodenectomy (PD) for pancreas adenocarcinoma (PC). Methods: All patients with resected PC in Ontario, Canada diagnosed 2004 to 2014 were identified and linked to administrative healthcare databases. Stratified Kaplan—Meier survival curves and log-rank test compared survival across treatment groups. Costs were assessed from the perspective of Ontario’s single-payer healthcare system and compared between CT and CRT. A one-year time horizon was used from the date of surgery. Results: 677 PC patients met all inclusion/exclusion criteria and underwent curative-intent PD with 77% receiving CT and 23% CRT. Median survival after resection was 21.7 and 18.9 months for CT and CRT groups, respectively. Patients receiving CRT were less likely to have high comorbidity burden (ADG ≥ 10), but were similar across other demographics. CRT patients were more likely to have margin positive disease. In a subgroup of 489 patients with margin negative disease, median survival in the node negative patients (n = 156) was 28.0 months for CRT and 24.7 months for CT (p = 0.8297, logrank). Median survival in the node positive patients (n = 333) was 20.6 months and 21.8 months for the CRT and CT patients, respectively (p = 0.9856, logrank). The median total one-year cost for CT was $52,575 (USD); CRT was $68,216 (Table 1). Conclusions: Patients who underwent adjuvant CT and CRT after PD for PC had similar overall survival, but healthcare expenditures were significantly higher in the CRT group. [Table: see text]
A multicenter cohort study of sunitinib (SU) versus imatinib (IM) dose escalation as second-line therapy in patients with gastrointestinal stromal tumors (GISTs) after disease progression of 400 mg/d IM.
Authors: Zhang Xinhua , Liu Xing , Wu Xiao Jun , Pan Zhizhong , Lu Hui-shan , He Yulong 
Published: January 2019

356 Background: Lacking of robust evidence from prospective trials, whether to choose IM dose escalation or to directly change to SU in patients failure on standardized 400mg/d dosing of IM is still controversial. Methods: The aim of this study, is to compare the efficacy of sunitinib and imatinib dose escalation as second-line therapy in patients with GIST previously treated with 400mg/d IM. Data of patients with recurrent/metastatic GISTs who was treated by SU from 2008.1 to 2016.12, in three tertiary teaching hospitals in southern China were analyzed from prospectively registered databases, respectively. Time to SU failure (TTSF) was defined as from the time of disease progression of 400mg/d IM to failure of SU treatment in both groups. Results: A total of 240 patients received SU at least 8 weeks were collected. SU was given in 37.5mg continuous daily dose or 50mg 4 weeks on/2 weeks off. Data of 203 patients (male 136, female 67) with complete follow-up were analyzed. The median age was 52.6 years, ranged 20-79 years. KIT/PDGFRA mutational analysis was performed in 151 patients. KIT exon 11 and 9 mutations were found in 79 (52.3%) and 39 (25.8%) patients, respectively. PDGFRA D842V was in five patients (3.3%), and KIT/PDGFRA WT in 26 patients (17.2%). After failure on 400mg/d IM, 100 (49.3%) patients had a dose escalation to 600mg/800mg per day (IM group), and 103 directly changed to SU(SU group). The progression-free survival (PFS) of IM group and SU group was 5.8m and 16.9m, respectively ( P<0.001). Either the TTSF or overall survival (OS) on both groups was not statistically different (18.3m VS 16.9m, P=0.219; 29.42m VS 29.45m, P=0.73). None of clinical factors that was correlated with survival using regress analysis, including primary site of lesion, metastatic sites, or mutational status, etc. Conclusions: This multi-center cohort study indicated better PFS in directly changed to SU than IM dose escalation when standardized dose IM failure. However, to those continued with SU therapy after failure of dose escalation, the outcome, both time to SU failure or OS, is similar.
Racial disparities in the receipt of adjuvant chemotherapy in patients with resected stage I-III pancreatic adenocarcinoma.
Authors: Sanford Nina Niu , Xu Xiaohan , Sher David J. 
Published: January 2019

357 Background: Adjuvant chemotherapy for resected pancreatic adenocarcinoma is a category 1 NCCN recommendation, however studies have shown that many patients do not go on to receive chemotherapy after definitive surgery. Whether racial disparities exist for receipt of adjuvant chemotherapy is unknown. Methods: The National Cancer Database was used to identify 28,255 patients with non-metastatic pancreatic adenocarcinoma who underwent definitive surgery between 2005-2014. Multivariable logistic regression defined adjusted odds ratio (AOR) and 95% confidence intervals (CI) of receipt of adjuvant chemotherapy by race. Additional variables included in the model were age, sex, stage, node positivity, comorbidity index, facility type and insurance. Among those receiving chemotherapy, multivariable logistic regression assessed odds of treatment with multiagent chemotherapy and among those not receiving chemotherapy, predictors of chemotherapy refusal were assessed. Results: Compared to white patients, black patients were less likely to receive adjuvant chemotherapy (AOR 0.74, 95% CI 0.64-0.85, p < 0.001) and multiagent adjuvant chemotherapy (AOR 0.80, 95% CI 0.72-0.88, p < 0.001). The disparities were limited to patients with comorbidity score of 0 and persisted when analyses were restricted to only academic cancer centers. Among 2,405 patients not treated with chemotherapy, black patients had lower odds of refusing chemotherapy (AOR 0.72, 95% CI 0.55-0.93, p = 0.01). Conclusions: In this nationally representative study, black patients were less likely to receive NCCN-guideline concordant treatment for resected pancreatic adenocarcinoma; this disparity did not appear to be driven by increased refusal of treatment by black patients. Given that differences in quality of care may contribute to disparities in cancer survival, our findings suggest that outcomes for black patients could be improved by increasing the proportion receiving guideline-concordant adjuvant chemotherapy. Further investigation is needed to identify factors leading to the observed differences in this study, such that appropriate interventions can be undertaken to mitigate this disparity.
Is rising BMI associated with an increased rate of clinically relevant pancreatic fistula after distal pancreatectomy for pancreatic adenocarcinoma?
Authors: Glazer Evan Scott , Zhou Yixuan , Drake Justin , Deneve Jeremiah Lee , Behrman Stephen W , Dickson Paxton Vandiver , Shibata David 
Published: January 2019

360 Background: Clinically relevant pancreatic fistula (CR-POPF), following distal pancreatectomy (DP) remains a clinical challenge. Prior studies investigating the relationship between body mass index (BMI) and CR-POPF have yielded conflicting results. We examined this relationship utilizing our institutional database and hypothesized that BMI is associated with CR-POPF in patients having DP for pancreatic ductal adenocarcinoma (PDAC). Methods: Patients who underwent DP for PDAC at a single institution from 2007 to 2018 were retrospectively reviewed. A CR-POPF was defined as ISGPS grade B or C fistula. Uni- and multi-variable logistic regression analysis to assess factors associated with CR-POPF following DP was performed, controlling for factors such as gland texture, operative drain placement, gender, and smoking status. Results: 78 patients met the inclusion criteria. 51% were female, 51% were Caucasian, and the average age was 59 ± 15 years. The median BMI was 26 (interquartile range 24 to 29). Overall, 19% (n = 15) of patients had a CR-POPF. With a mean follow up 2.8 ± 2.5 years, the presence of a CR-POPF was not associated with long-term survival (P = 0.17). On univariable logistic regression, older age was associated with a decreased risk of CR-POPF (OR = 0.95, P = 0.015) while increasing BMI was associated with an increased risk of CR-POPF (OR = 1.1, P = 0.044). After controlling for multiple factors on multivariable logistic regression analysis, BMI (OR = 1.12, P = 0.035) was the only factor associated with development of a CR-POPF while older age (OR = 0.94, P < 0.001) was slightly protective of CR-POPF development. Conclusions: For patients undergoing DP for PDAC, increasing BMI is associated with an increased risk of CR-POPF, independent of other factors. These findings should be considered during preoperative counseling. Although there is no specific cut-off for the association between BMI and CR-POPF, efforts to diminish the risk of CR-POPF should be focused on patients with higher BMI based on this data.
Outcomes of tyrosine kinase inhibitors (TKI) after immunotherapy in unresectable or advanced hepatocellular carcinoma (HCC) patients.
Authors: Yau Thomas Cheung , Tang Vikki , Chan Jess , Kwok Gin Wai , Chiu Joanne , Leung Roland Ching-Yu , Li Bryan , Cheung Tan To 
Published: January 2019

361 Background: The outcomes of tyrosine kinase inhibitor(TKI) treatment after immune checkpoint inhibitors (PD-1i, PD-L1i, CTLA-4i) in unresectable/advanced HCC population is largely unknown. Methods: Retrospective analysis of advanced HCC patients treated with immune checkpoint inhibitors followed by TKI therapy at Queen Mary Hospital, Hong Kong were reviewed for the outcomes. Patients received locoregional therapy immediately after immunotherapy were excluded. Results: From January 2016 to July 2018, 30 HCC patients (83% of HBV, 80% of Child Pugh A, 83% of EHS/ MVI, median AFP=1,353ng/mL) who received TKI (11 lenvatinib, 10 sorafenib, 6 regorafenib, 3 axitinib) after immunotherapy were identified. TKI post-immunotherapy ("index TKI") was administered as third-line or beyond in 70% of patients. At the time of analysis (September 2018), median duration of index TKI was 72 days (IQR 36- 119∗) (∗3 patients were still receiving TKI). AFP declined in 53% of patients and the median change from baseline to nadir was -25% (IQR -65% to +6%). 40% of patients received subsequent systemic therapy. Median OS from index TKI was 602 days (95%CI 124-not reached; death event rate: 47%). 3 patients achieved partial response to TKI and they had at least stable disease with the previous immunotherapy. No unexpected safety issues of TKI and death related to adverse events were noted (table). Conclusions: TKI is active with good tolerabilty following immunotherapy in advanced HCC patients.[Table: see text]
A nationwide multicenter study in patients with unresectable hepatocellular carcinoma treated with lenvatinib in real world practice in Japan.
Authors: Tsuchiya Kaoru , Kurosaki Masayuki , Kaneko Shun , Kimura Toru , Marusawa Hiroyuki , Arai Hirotaka , Abe Takehiko , Kimura Hiroyuki , Tsuji Keiji , Furuta Koichiro , Ogawa Chikara , Narita Ryoichi , Kojima Yuji , Akahane Takehiro , Uchida Yasushi , Yoshida Hideo , Kobashi Haruhiko , Kusakabe Atsunori , Joko Kouji , Izumi Namiki ,   The Japanese Red Cross Liver Study Group
Published: January 2019

364 Background: Lenvatinib(LEN) has been approved as a single agent for patients with unresectable hepatocellular carcinoma (u-HCC) since Mar 2018 in Japan. A few results from a large sample size cohort of LEN therapy in real world practice has been reported. Therefore, we performed a retrospective nationwide multicenter study. Methods: A total of 116 u-HCC patients received LEN from March 2018 at 14 sites in Japan were registered. Tumour assessments in accordance with RECICT ver1.1 and modified RECIST were done using dynamic CT or MRI within 4-8 weeks and every 6-8 weeks thereafter. Adverse events (AEs) were graded according to the CTCAE ver4.0. Results: Median age was 72 (46-91)years, 88 (75.9%) patients were male, and median body weight was 60 (30-94) kg. The baseline liver function was Child-Pugh class A in 106 (91.4%) patients. Seventy-three (62.9%) patients were BCLC stage C. As the 2nd-line therapy (after sorafenib), 28 (24.1%) patients received LEN and 17 (14.7%) patients did as the 3rd-line (after regorafenib). Median observation time was 2.5 months and one patient died from HCC progression. The imaging findings of 49 (42.2%) patients were evaluated at 4-8weeks. Based on mRECIST, CR was shown in 3 (6.1%), PR in 14 (28.6%), SD in 23 (46.9%), and PD in 6 (12.2%). In the 3 patients, target lesions of liver showed PR, however bone metastases had progressed. [overall response rate (ORR) 34.7%, disease control rate (DCR) 81.6%]. ORR and DCR of tyrosine kinase inhibitor (TKI) naïve patients (n = 26) were 34.6% and 80.8%, while those of TKI experienced (n = 23) were 34.8% and 82.6%. The most common any-grade AEs were hypertension (52.0%), diarrhoea (32.1%), decreased appetite (63.5%) and fatigue (49.4%). Hand-food skin reaction (HFSR) was observed in 28% of patients. Conclusions: The efficacy of LEN therapy in real world practice in Japan was similar to the phase 3 clinical trial, even though elderly patients with lower body weight were included in this study. The incidence of HFSR during LEN in real world practice was lower than that of the sorafenib group in the phase 3 trial of LEN. Decrease appetite and fatigue must be carefully monitored and managed during LEN therapy.
Subsequent anticancer medication following first-line lenvatinib: A posthoc responder analysis from the phase 3 REFLECT study in unresectable hepatocellular carcinoma.
Authors: Alsina Angel , Kudo Masatoshi , Vogel Arndt , Cheng Ann-Lii , Tak Won Young , Ryoo Baek-Yeol , Evans T.R. Jeffry , López-López Carlos , Daniele Bruno , Misir Soamnauth , Ren Min , Izumi Namiki , Qin Shukui , Finn Richard S. 
Published: January 2019

371 Background: Lenvatinib (LEN) was shown to be noninferior to sorafenib (SOR) for overall survival (OS) in REFLECT (median OS [mOS], 13.6 vs 12.3 months [mo]; HR 0.92; 95% CI 0.79–1.06). LEN was superior vs SOR for secondary endpoints including objective response rate (ORR) per mRECIST: 24.1% vs 9.2% by investigator and 40.6% vs 12.4% by independent review (Kudo M et al. Lancet 2018). We report a posthoc responder analysis of patients (pts) who received first-line LEN in REFLECT and subsequent anticancer medication during survival follow up. Methods: In REFLECT, pts with unresectable hepatocellular carcinoma were randomized 1:1 to receive first-line LEN or SOR. Objective response was defined as complete or partial response by mRECIST per investigator. Pts with disease progression and who discontinued treatment were followed for survival every 12 weeks; subsequent anticancer medication during survival follow up were recorded until time of death. Data cutoff: Nov 13, 2016. mOS was calculated using Kaplan-Meier estimates with 2-sided 95% CIs. Results: In REFLECT, one third of the overall study population (156/478 pts randomized to LEN and 184/476 to SOR) received subsequent anticancer medication, most commonly SOR (25% in LEN arm). ECOG performance status and laboratory assessments, including liver function tests, were comparable between arms prior to subsequent treatments. Among these pts, mOS was 21 vs 17 mo and ORR was 27.6% vs 8.7% for LEN vs SOR arms, respectively. In a subset analysis of LEN responders who received any subsequent anticancer medication (n = 43), mOS was 26 mo (95% CI 18.5–34.6). For SOR responders who received any subsequent anticancer medication (n = 16), mOS was 22 mo (95% CI, 14.6–NE). For LEN responders who subsequently received SOR (n = 35), mOS was 26 mo (95% CI 18.2–34.6). Conclusions: In REFLECT, one third of pts randomized to first-line LEN received subsequent anticancer medication, including SOR, with a mOS of 21 mo. In this exploratory, posthoc analysis of pts who responded to LEN and received any subsequent anticancer medication or SOR, mOS was 26 mo. Clinical trial information: NCT01761266.