bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival of older patients with advanced biliary tract cancers by disease site.
Authors: Bobiak Sarah , Lubeck Deborah P. , Duryea Jennifer , Danese Mark D. 
Published: May 2020

e16598 Background: Biliary tract cancers (BTC) arise from the epithelial lining of the biliary tree and include intrahepatic and extrahepatic cholangiocarcinoma, gallbladder cancer, and sometimes cancer of the ampulla of Vater. Although this is a closely related group of diseases, comparisons of risk factors, treatment, and mortality by disease site are limited. Methods: This retrospective cohort study used Surveillance, Epidemiology, and End Results (SEER) cancer registry data linked with Medicare claims. Patients aged ≥66 years with a pathologically confirmed diagnosis of advanced (stage III or IV) BTC from 2010 to 2015 were included and followed up through 2016. Patients with any SEER-reported cancer in the prior 2 years were excluded. Any outpatient systemic treatment during follow-up was identified using Medicare claims. Patients were followed up until death, end of follow-up, subsequent primary cancer, or switch to managed care. The Kaplan-Meier estimator was used to estimate unadjusted median survival. A Cox proportional hazards model was used to identify factors associated with survival. Results: There were 2,891 patients in the cohort (Table). Factors significantly associated with worse survival included older age, presence of mobility limitations, living in an area with > 30% of the people below poverty, higher comorbidity burden, and stage IV BTC (vs stage III). Factors significantly associated with better survival included history of cancer, intrahepatic BTC (vs extrahepatic), or ampulla of Vater BTC (vs extrahepatic). Conclusions: Survival in BTC is poor and many patients do not receive outpatient systemic therapy. Patients with gallbladder and extrahepatic BTC had worse median survival and were less likely to receive systemic therapy than those with intrahepatic or ampulla of Vater BTC. Fewer ampulla of Vater patients present with Stage IV disease which could be a contributing factor to the significantly longer survival. Prior work has demonstrated an association between history of some types of cancer and survival; additional research is needed to better understand this finding. [Table: see text]
A phase Ib/II, open-label study of tivozanib in combination with durvalumab in subjects with untreated advanced hepatocellular carcinoma.
Authors: Iyer Renuka V. , Li Daneng , Dayyani Farshid , Needle Michael N. , Abrams Thomas Adam 
Published: May 2020

e16599 Background: VEGFR TKIs and checkpoint inhibitors are current standards of care in HCC as single agents, however treatment options are limited, and significant unmet need remains. A recent ph3 study combining bevacizumab (VEGF-A Mab) with a PDL1 inhibitor have shown promising improvements in OS demonstrating that a combination of VEGF and PDL1 inhibition can improve patient outcomes over single agent treatment. Tivozanib (T, a potent and selective VEGFR 1, 2 & 3 TKI) and durvlaumab (D, a PD-L1 antibody) have both demonstrated single agent activity in HCC and have been combined safely with other therapies to enhance patient outcomes in other tumor types. It is hypothesized that more complete inhibition of the VEGF pathway by tivozanib compared to bevacizumab combined with PDL1 inhibition may further enhance patient outcomes. The ph1 portion of this study combines T with D to establish the recommended phase 2 dose (RP2D) and provide preliminary safety and efficacy data. Methods: Major eligibility criteria are adults with documented advanced HCC, Child-Pugh Class A, ECOG 0 or 1, creatinine clearance > 40 ml/min. Major exclusion criteria are co-infection with HBV and either HDV or HCV and significant organ dysfunction. Six patients with untreated advanced HCC will be treated with the combination of T 1 mg orally for 21 days followed by 7 days off treatment and D 1500 mg intravenously every 28 days. A DLT is generally defined as the occurrence of any Grade ≥3 immune or non-immune AE in Cycle 1 that is at least possibly related to the investigational regimen other than any grade of vitiligo or alopecia or Grade 3 controllable hypertension. If two or more patients have a DLT then the dose of tivozanib will be reduced to 1 mg every other day without interruption for the second cohort. In the Phase 2 portion of the study an additional 30 patients will be treated at the RP2D. The primary objective is to establish the RP2D and the safety and tolerability for this combination in patients with advanced HCC. Secondary objectives are to assess the objective response rate, progression free survival, and overall survival in this population. Patients will be treated until progression of disease, unacceptable side effects, or death. Outcome measures will be adverse events per CTCAE v.5 and cross-sectional imaging performed every 8 weeks. Results: Phase 1 safety and efficacy findings for this novel combination will be reported at the meeting. Conclusions: Phase 1 safety and efficacy findings for this novel combination will be reported at the meeting. Clinical trial information: NCT03970616 .
Does time to treatment initiation affect survival in patients with gallbladder cancer?
Authors: Islam KM , Odhiambo Lorriane Achieng , Ansa Benjamin , Copur Mehmet Sitki 
Published: May 2020

e16600 Background: Gallbladder cancer (GBC) is the most aggressive malignancy of the biliary tract. Though rare, most diagnoses are made in advanced stages, which significantly impacts survival outcomes. In the U.S., only 20% of GBC cases are diagnosed early. In addition to late diagnosis, time to treatment initiation (TTI) after diagnosis may contribute to poor prognosis in GBC patients. The role TTI plays on survival is not well understood in patients with GBC. This study aimed to determine the effect of time to treatment initiation on overall survival and by stage. Methods: Data on 26,952 GBC patients from 2004 to 2012 were obtained from the National Cancer Database (NCDB). The primary outcome was overall survival in months. TTI was defined as the number of days between diagnosis and treatment initiation (surgery, chemotherapy, radiation). The Kaplan-Meier method was used to calculate survival estimates and Cox proportional hazards regression model to evaluate the effects of TTI (continuous variable) stratified by stage. Results: The overall median survival was 8.6 months (I.Q.R. = 2.6-23.9). The effect of TTI on survival (unadjusted Hazard Ration (UHR) 1.0 (p = < 0.0001)) was significant, but not after adjusting for other variables, (adjusted Hazard Ratio (AHR) 1.0 (p = 0.1506)). The trend was different across cancer stages. TTI showed a negative effect on survival in stages III (AHR: 1.00, p = 0.0083) and IV (AHR: 0.99, p < .0001). Other factors associated with lower survival are advanced stage, male, older age, comorbidity, community cancer facility, and whether a patient visited more than one facility for treatment. Conclusions: In general, time to treatment initiation did not affect survival but advanced stage lowered survival significantly. More attention should be given to patients who decide to seek second opinion at or those given treatment referrals to other facilities as the adjustments may contribute to delays in treatment initiation.
Hepatic artery infusion chemotherapy combined with apatinib and toripalimab in advanced hepatocellular carcinoma: Real-world data from a single center.
Authors: Gu Yang-Kui , Zhang Tian-Qi , Huang Zi-Lin , Geng Zhi-Jun , Chen Chen , Li Fu-Gui , Xu Li , Sun Jian , Li Jibin , Huang Zhi-Mei , Shen Lujun 
Published: May 2020

e16602 Background: Outcomes remain poor for patients with advanced hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC), antiangiogenic agents, and immune checkpoint inhibitors (ICIs) are available monotherapy options. Considering different anti-malignancy mechanisms, combining these three modalities may improve outcomes. We aimed to assess the efficacy and safety in a small cohort treated with HAIC combined with Apatinib and ICI (Toripalimab) for advanced HCC patients. Methods: We performed a retrospective study included patients with advanced HCC treated in the Sun Yat-sen University Cancer Center. Patients received 6 treatment cycles of 21 days, with HAIC given over an initial period of 50 hours (oxaliplatin 85 mg/m2, then folinic acid 400 mg/m2, then fluorouracil 2500 mg/m2). Patients also received apatinib (250 mg daily, starting day 8 of cycle 1), toripalimab (240 mg on day 4 of each cycle, starting with cycle 2), both continuing after the HAIC cycles until disease progression. Disease control was assessed using the RECIST 1.1 and mRECIST criteria. Safety was assessed using the CTCAE 5.0. Blood biomarkers (AFP and PIVKA-II) were log transferred and compared at baseline and last follow-up. Results: From April to August 2019, 6 patients (5 males, 51.7±11.6 years) were included. All patients finished 6 cycles of HAIC. After a median follow-up of 7.0 (range, 3.9-8.3) months, all patients remained objective response (6 PR by RECIST; 3 CR and 3 PR by mRECIST). Median time to response was 1.3 (range, 0.7-2.0) months. Blood logAFP (baseline: 3.2±1.6, last follow-up: 1.3±1.4; p = 0.029) and logPIVKA-II (baseline: 4.4±0.6, last follow-up: 2.0±1.4; p = 0.006) levels were significantly decreased after treatment. The most common adverse events (AEs) included hypertension, palmar-plantar erythrodysesthesia syndrome, and anorexia, observed in all patients. Four patients had Grade 3 AEs (myelosuppression in 2; palmar-plantar erythrodysesthesia, hypothyroidism, anorexia, hyperbilirubinemia and hypokalemia in 1). No Grade 4/5 AEs occurred. Conclusions: In patients with advanced HCC, treatment with strategically timed triple combination therapy of HAIC, apatinib, and toripalimab shows promising clinical benefit and safety. [Table: see text]
Treatment outcome and prognostic indicators in 26 cases of fibrolamellar hepatocellular carcinoma under interferon based therapy.
Authors: Mohamed Yehia I. , Qayyum Aliya , Hassan Manal , Xiao Lianchun , Duda Dan G. , Hatia Rikita , Lee Sunyoung S. , Wolff Robert A. , Morris Jeffrey , Altameemi Lina , Yao James C. , Amin Hesham M. , Kaseb Ahmed Omar 
Published: May 2020

e16626 Background: Fibrolamellar hepatocellular carcinoma (FLHCC) is a variant of HCC that comprises ∼1%–9% of all HCCs, with about 200 annual cases reported globally, most often affects younger patients (10–35 years of age) with no underlying liver disease. There is no current standard of care therapy for unresectable FLHCC. We report an analysis of the treatment outcomes, and prognostic indicators of 26 cases. Methods: We retrospectively collected clinicopathologic and treatment outcome data from 26 FLHCC patients who received interferon alfa-2b (IFN) based therapy. Median overall survival (OS) and PFS were calculated using Kaplan-Meier curves, and survival rates were compared by the log-rank test. Results: 21 patient underwent treatment with continuous infusion (CI) 5-Fluorouracil (FU) at 200 mg/m2/day for 7 days on, 7 days off plus IFN at 4 million units/m2, subQ every other day for 7 days on, 7 days off, 1 patient FU+IFN+bevacizumab and 4 patients had PIAF (cisPlatin+IFN+Adriamycin+FU). Median age was 24 years (15-44), 13 males and 13 females, 8 of the 26 patients died, the median overall survival was 33.9 months (95% CI, 20.9, NA), estimated 3-year survival was 20.2% (95% CI: 4.1%, 98.5%), median follow up time was 13.4 months (95% CI: 9.79, NA) and median progression-free survival was 11.7 months (95% CI: 5.09, NA). The estimated 1-year survival was 47.9% (95% CI: 29.9%, 76.8%). Finally, FU+IFN combination was the most frequently used systemic therapy. 3/26 pts underwent surgical resection following neoadjuvant treatment with interferon based therapy; Interferon based therapy for the 26 patients had limited side effects, with only 3 of the 26 patients discontinued treatment due to grade 3-4 adverse event in the form of mucositis, severe fatigue and/or hematologic toxicity. Conclusions: Our analyses indicate that CI FU + IFN could be an effective treatment for FLHCC, and may have a neoadjuvant role in this disease with 3/26 were resectable following neoadjuvant treatment with interferon based therapy. This regimen can be well tolerated. Unfortunately, nonsurgical options for patients with FLC remain limited with no approved local or systemic therapies. Therefore, future research is needed to identify better multimodality therapies.
Long-term outcome analysis of Y90 radioembolization in hepatocellular carcinoma.
Authors: Alder Laura , Nguyen Matthew , Qu James , Lee Hannah , Thacker Leroy R. , Dougherty Sean , Poklepovic Andrew Stewart 
Published: May 2020

e16633 Background: Yttrium-90 (Y90) radioembolization is a catheter-based therapy utilized in the treatment of hepatic tumors such as hepatocellular carcinoma (HCC). Multiple trials have evaluated the efficacy of Y90 in HCC; few have assessed long term hepatic function. These studies reported PFS ranging from 7.9 to 18 months (m), and median OS of 17.2 to 18 m for Child-Pugh (CP) Class A and 6.0 to 7.7 m for CP Class B. This study aimed to evaluate a clinical real-world experience of Y90 therapeutic effectiveness and long-term impact on hepatic function. Methods: A single-center retrospective chart review was performed for patients with a CP score of A or B who received Y90 for primary HCC between 2008 and 2016. Model for end stage liver disease (MELD) and CP scores were calculated for the day of treatment and at 1, 3, 6, 12, and 24 m post procedure. OS and PFS were characterized using a Kaplan-Meier survival analysis and a multivariate model. Results: 134 patients were included. Mean age was 60 years old, ranging from 44-90. Underlying liver disease included HCV – 66%, ETOH cirrhosis – 23%, NAFLD – 19%, HBV – 5%. CP Class A patients (79%) had a median OS of 16.59 m (95% CI: 8.90 to 23.10m) from date of Y90 treatment compared to a median of 7.90 m (95% CI: 4.60 to 15.64 m) for CP Class B. CP Class A patients had a median PFS of 3.45 m (95% CI: 2.99 to 5.55 m) from date of Y90 treatment compared to a median of 3.71 m (95% CI: 2.07 to 8.28 m) for CP Class B patients. These differences were not statistically significant. Median OS from date of diagnosis for the entire study population was 29.37 m (95% CI: 23.00 to 38.77 m). MELD scores were statistically significantly higher at 1, 3, 6 and 12 m post-treatment than on Day 0, with significant recovery at 24 vs 3 m. Older age, higher T stage, higher MELD and CP scores, and patients with a history of portal vein thrombosis (PVT) had significantly lower OS. PFS was significantly shorter in those with advanced stage at diagnosis and higher CP score. Conclusions: While our study supports the literature for OS in Y90 patients, we found a shorter PFS in this population. This may reflect the utilization of RECIST in clinical trials vs clinical radiology practice in determining progression. Over time, the most significant factors associated with OS were age, MELD and CP scores and PVT. For PFS, CP score and stage at diagnosis were significant. The increasing MELD and CP scores over time reflect a possible mix of radio embolization‐induced liver disease and progression of HCC. The downtrend at 24 m is likely due to durable survivors with significant benefit from therapy and no long-term complications from Y90.
A phase Ib/II study of olutasidenib in patients with relapsed/refractory IDH1 mutant solid tumors: Safety and efficacy as single agent.
Authors: Jones Robin Lewis , Macarulla Teresa , Charlson John A. , Van Tine Brian Andrew , Goyal Lipika , Italiano Antoine , Massard Christophe , Rosenthal Mark , De La Fuente Macarena Ines , Roxburgh Patricia , Kundranda Madappa N. , Blay Jean-Yves , Yoo Changhoon , Lipford Kate , Forsyth Sanjeev , Guichard Sylvie Mireille , Mikhailov Yelena , Thomson Blythe , Kelly Patrick Francis , Duffaud Florence 
Published: May 2020

e16643 Background: Isocitrate dehydrogenase 1 mutations (mIDH1) are present in a variety of solid tumors resulting in production and accumulation of (R)-2-hydroxyglutarate causing DNA hypermethylation and promoting tumorigenesis. Olutasidenib is an oral, potent and selective inhibitor of mutated IDH1 protein. We report preliminary results from the ongoing, first-in-human, Phase 1, open-label, single-arm study of olutasidenib in non-CNS solid tumors. Methods: Patients with advanced relapsed/refractory (R/R) mIDH1 solid tumors received olutasidenib 150 mg BID, orally. Following a dose confirmation cohort (Phase 1b), patients with intrahepatic cholangiocarcinoma (IHCC), chondrosarcoma (CS), or unspecified mIDH1 solid tumors (Other) were enrolled in a Phase 2 efficacy evaluation (NCT: 03684811). Results: As of 31-Oct-2019, 44 patients with relapsed or refractory mIDH1 solid tumors were treated with olutasidenib. Diagnosis included: IHCC (n = 26), CS (n = 13), and Other (n = 5). The median age was 58 years (range: 29-81) and 43% were male. Median number of prior treatments was 2 (1-10). mIDH1 status was locally determined (IHC, NGS or PCR): R132C (61%), R132G (7%), R132S (7%), R132H (2%), R132L (2%), Others (2%) & unspecified (18%). Fourteen patients discontinued treatment (disease progression [n = 6; 3 IHCC, 2 CS, 1 Other], AE [n = 4; 3 IHCC, 1 CS], PI decision [n = 3; IHCC] & withdraw consent [n = 1; IHCC]). Treatment emergent adverse events (all grades, regardless of attribution) that occurred in > 15% of pts were: nausea (43%), fatigue (25%), decreased appetite (22%), AST increase (18%), ALT increase (16%), and constipation (16%). No protocol-defined DLTs occurred. Best responses by tumor type are shown in the table. Conclusions: Single agent olutasidenib at 150 mg BID demonstrates acceptable safety and tolerability with preliminary clinical activity in patients with R/R mIDH1 solid tumors. Updated safety and clinical activity, as well as exploratory evaluations of PK/PD will be provided. Clinical trial information: 03684811 . [Table: see text]
Clinical characteristics and outcomes of patients with advanced hepatocellular carcinoma treated with immunotherapy: A “real world” retrospective study.
Authors: Chergui Adel , Gadde Eswar , Acuna-Villaorduna Ana , Kabarriti Rafi , Goel Sanjay , Kaubisch Andreas 
Published: May 2020

e16644 Background: Advanced hepatocellular carcinoma (HCC) is an aggressive malignancy with dismal prognosis. Newer agents, including immunotherapy (IO), have been granted accelerated approval for patients previously treated or unable to tolerate sorafenib. However, information outside clinical trials is scarce. This study aims to describe clinical characteristics and outcomes of HCC patients treated with IO. Methods: HCC patients treated with IO were identified using the institutional software, Clinical Looking Glass. Data regarding demographics, clinical and treatment characteristics were collected by chart review. Neutrophil/lymphocyte ratio (NLR) and AFP were collected at IO treatment initiation and considered low if below 4 and 400, respectively. Progression-free survival (PFS) was defined as time from treatment initiation to progression of disease or death, and overall-survival (OS) as time from IO initiation to death from any cause. Disease characteristics were analyzed using descriptive statistics, PFS and OS were plotted using Kaplan-Meier curves. Results: 52 patients with a median age of 64.5 years and male predominance (38, 73.1%) were identified. There were 24 (54.5%) Hispanics, 9 (20.5%) Non-Hispanic Blacks, 7 (15.9%) Non-Hispanic White and 4 (9.1%) Asians. Cirrhosis present in 41 (83.7%), median MELD of 8 (IQ: 7-10). 37 (77.1%) patients had ECOG 0-1. Hepatitis B and C and B infection were encountered in 12 (24.5%) and 22 (44%) patients, respectively. Intravascular invasion present in 16 (34.8%) and extrahepatic metastases in 7 (14.9%). Local treatment was provided to 29 (59.2%) and radiation to 14 (28.6%). First line treatment (tx1) was Sorafenib in 29 (55.8%) and Nivolumab in 21 (40.4%). Nivolumab was second line treatment or beyond (tx2) in 31 (59.6%). Median PFS was 6.2 (3.1-10.6) months and it did not differ between tx1 and tx2 (8 vs 5.9 months, p = 0.90). Median OS was 13.2 months; there was a tendency towards higher survival rates in patients that were treated in tx2 (11.8 vs 14.3 months, 0 = 0.59) and in patients with low NLR (14.8 vs 9.2 months, p = 0.14). Median OS was higher in patients with low AFP at IO treatment initiation (15.7 vs. 9.2 months, p = 0.03). Conclusions: In this multiethnic cohort, the “real world” experience of the benefit of IO in HCC is encouraging, with a median OS exceeding one year. NLR showed potential as a possible biomarker. Expanded data may elucidate the differences if any, between use of IO as front vs. second line therapy, in PFS and OS.
Clinical effect of sequential therapy of LEN combination with anti-PD1 antibody in uHCC patients who progressed on LEN treatment: A real-world data in China.
Authors: Chen Yi , Zhang Lan , Ge Ningling , Wang Yanhong , Ren Zhenggang 
Published: May 2020

e16654 Background: Lenvatinib (LEN) has been used in clinical practice because of its high response rate since administrated in China. However, no recommendation is available as second-line agents after LEN treatment. The combination therapy of anti-programmed death-1(PD1) antibodies with LEN have demonstrated promising clinical efficacy in advanced HCC. Some patients were used this combination treatment after progressed on LEN in real world settings in China. Preclinical studies also showed the immune-moderate effects of LEN. This study was retrospectively analyzed the efficacy and safety of 26 unresectable HCC patients treated with LEN and anti-PD1 antibody after progressed on LEN. Methods: Unresectable HCC (uHCC) patients who treated with the combination of LEN with anti-PD1 antibody after progressed on LEN were enrolled. Patients who combine other loco-treatment and systemic therapy during the LEN combination with PD-1 antibody treatment period were excluded. The efficacy of LEN and anti-PD1 antibody was evaluated by mRECIST criteria after 2 cycles of combination treatment. AE data were recorded during the combination treatment period. Results: From October 2018 to October 2019, 26 patients were finally enrolled. As of January 10, 2020, median follow-up was 6.7±3.19 months. Median age was 56.15±11.9 years old, 80.77% (21/26) was Child-pugh(CP) A while 19.23% (5/26) was CPB7 and 88.5% (23/26) was BCLC stage C. Before combination therapy, 11 patients (42.31%) used LEN only and the other 15 patients (57.69%) were experienced sorafenib/chemotherapy before LEN. Drugs of PD1 antibodies were Keytruda and Toripalimab. The median duration of combination treatment was 6.7±3.15months. The ORR was 26.9% in total 26 cases. 2 cases of them were complete response, and the disease control rate (DCR) was 88.5% (23/26). The most common adverse events (AEs) of combination treatment were hypertension (42.31%), diarrhea (38.46%), hypothyroidism (38.46%) and anorexia (34.62%). Grade 3 or higher AEs occurred in 6 (23.08%) patients. Conclusions: This was the first real-world data of sequential therapy of LEN combination with anti-PD1 followed LEN in uHCC patients. For advanced patients who have progressed after LEN treatment, the results were promising, showing high DCR and well tolerated. 2 cases even achieve complete response. Sequential therapy may be an option for these patients. The efficacy of combination treatment needs random clinical trial to be further studied.