bluuebunny/crossref_metadata_2025 huggingface dataset:
Lenvatinib plus pembrolizumab versus lenvatinib in patients with unresectable hepatocellular carcinoma: A real world study.
Authors: Lee I-Cheng , Wu Chi-Jung , Chen San-Chi , Chao Yee , Huang Yi-Hsiang
Published: June 2021

e16138

Background: The combination of lenvatinib (LEN) and pembrolizumab (PEMBRO) showed promising response rates and survival in a phase 1b trial for patients with unresectable hepatocellular carcinoma (HCC). Whether LEN plus PEMBRO provides better outcomes than LEN monotherapy remains unclear. The aim of this study was to compare the outcomes of LEN plus PEMBRO versus lenvatinib monotherapy in patients with unresectable HCC in the real world setting. Methods: A total of 123 patients with unresectable HCC were retrospectively enrolled, including 61 patients with LEN monotherapy and 62 patients with LEN plus PEMBRO. We evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and disease control rate (DCR) by RECIST 1.1 and modified RECIST (mRECIST) criteria. Results: One hundred and one (82.1%) patients were in BCLC stage C and 81 (65.9%) patients received LEN or LEN plus PEMBRO as first line setting. During a median follow-up period of 8.0 months, 71 (57.7%) and 31 (25.2%) of patients had disease progression and death, respectively. The median PFS was 8.4 and 4.9 months in the LEN plus PEMBRO and LEN monotherapy groups, respectively (p = 0.033). The median OS was not reached in the LEN-PEM group and was 17.2 months in the LEN monotherapy group (p = 0.064). Patients with LEN plus PEMBRO had higher objective response rate (ORR: 34.4% vs 23.7% by RECIST 1.1, p = 0.277; 57.4% vs 32.2% by mRECIST, p = 0.010) and higher disease control rate (83.6% vs 62.7% by RECIST 1.1, p = 0.017; 85.2% vs 62.7% by mRECIST, p = 0.009). In subgroup patients with BCLC stage C, LEN plus PEMBRO provided significantly longer PFS (9.1 vs 4.8 months, p = 0.008), higher ORR (60% vs 33.3%, p = 0.015) and higher DCR (88% vs 60.4%, p = 0.004) by mRECIST criteria. Conclusions: LEN plus PEMBRO provides significantly better ORR, DCR and PFS then LEN monotherapy for patients with unresectable HCC.
A novel sub-staging system for prognosis prediction of Barcelona clinic liver cancer C stage hepatocellular carcinoma: 10 years observational study.
Authors: Mo Zhiqiang , Mai Qicong , He Jian , Chen Xiaoming
Published: June 2021

e16139

Background: This study sought to propose a novel sub-staging system which could predict prognosis of patients with Barcelona clinic liver cancer (BCLC) C stage Hepatocellular carcinoma (HCC). Methods: Between January 2008 and September 2018, 806 patients with BCLC-C stage HCC were assessed retrospectively. The significance of clinical variables in predicting prognosis were statistical analysis. A prognostic sub-staging system of BCLC-C stage HCC was developed according to prognosis-related factors. The predictive performance was subsequently validated. Results: In training set, tumor burden (TB) >50%, type III/IV portal vein tumor thrombus (PVTT), extrahepatic metastasis (M) and Child-Pugh (CP) B class were independently associated with overall survival (OS). According to those prognosis-related factors, a novel sub-staging system of BCLC-C stage was “linear predictor= TB+PVTT+M+CP”, which had good performance in predicting OS in both training and validation set. The thirtieth percentile and the third quartile of the linear predictor, namely 6 and 12, were selected as cut-off values, stratifying patients into different OS after interventional therapy (IT) or sorafenib therapy (ST), specifically, ≤6: 43.7 months for IT, 32.0 month for ST;＞6 but＜12: 43.7 months for IT, 32.0 month for ST; ≥12: 43.7 months for IT, 32.0 month for ST. Conclusions: The novel sub-staging system of BCLC-C stage HCC may stratify patients for suitable therapy and predict individual survival with favorable performance and discrimination.
Healthcare utilization and costs in hepatocellular carcinoma (HCC) patients treated at a large referral center in Washington (WA) State.
Authors: Shankaran Veena , Chennupati Shasank , Sanchez Hayley , Sun Qin , Aly Abdalla , Marcus Healey , Seal Brian S.
Published: June 2021

e16149

Background: Though the treatment landscape for HCC has changed significantly in the last several years with the refinement of liver-directed therapy techniques and the introduction of multiple new drugs, few studies have investigated the impact of the changing treatment landscape on lifetime treatment costs, particularly in Barcelona Clinic Liver Cancer (BCLC) stage C disease. We therefore sought to investigate real-world clinical characteristics, treatment patterns, healthcare use, and costs in patients with HCC treated at a single high-volume institution in WA. Methods: We conducted a retrospective cohort study of patients diagnosed with HCC between 2007 and 2018 at a single clinical cancer center using a database containing abstracted data from the electronic medical record (EMR) linked to cancer registry data and health claims from commercial insurance plans, Medicare, and Medicaid. We described clinical characteristics, including BCLC stage and Child Pugh score, and treatment patterns. We investigated the mean per patient lifetime treatment costs by BCLC stage using Kaplan-Meier cost estimator methods. Results: The final cohort included 215 patients, majority white (71%), male (68%), and with underlying hepatitis C (61%). Most patients had either Child Pugh A (76%) or B (20%) liver disease and BCLC A (45%), B (20%), or C (19%) stage HCC. Only 40% of BCLC C patients received systemic chemotherapy. Mean per patient lifetime costs were highest in BCLC A ($289,318) and BCLC C ($255,430) patients and lowest in BCLC D ($123,701) patients (Table). Surgical costs, hospital costs, imaging, and outpatient visits were the major contributors to total lifetime costs in BCLC A patients. Chemotherapy costs were highest in BCLC C patients, but still were not the predominant area of spending. Conclusions: In a WA state cohort of HCC patients, mean lifetime costs were highest in patients with BCLC A disease, largely driven by surgery and hospital costs. As utilization of newer and less toxic therapies in BCLC C patients increases, mean lifetime costs in this group may surpass other stages.[Table: see text]
Serum neutrophil/lymphocyte ratio as a potential predictor of treatment response for immune checkpoint inhibitors in patients with advanced hepatocellular carcinoma.
Authors: He Jian , Mo Zhiqiang , Mai Qicong , Chen Xiaoming
Published: June 2021

e16156

Background: Neutrophil to lymphocyte ratio (NLR) has been shown to associate with tumor progression. The present study was to investigate the role of NLR on predicting the treatment response for immune checkpoint inhibitors (ICIs) therapy in patients with advanced hepatocellular carcinoma (HCC). Methods: We retrospectively reviewed 81 patients received ICIs for advanced HCC from January 2017 to July 2019. We analyzed whether pre- and first 3 weeks post- treatment serum NLR level was associated with ICIs outcome. Results: In this study, the pre-treatment NLR level ranged from 0.64 to 14.93 among 81 patients. The cut-off level of NLR was set as the median value of 2.79. The objective response rate (ORR) in the patients with NLR＜2.79 (low NLR) was 25.0%, which was significantly better than that of patients with NLR ≥2.79 (high NLR) (7.3%, P ＝0.03). Compared to patients with high NLR, patients with low NLR exhibited significantly longer median progression-free survival (PFS) (3.7 vs 3.0 months, P ＝0.004) and median overall survival (OS) (10.3 vs 7.5 months, P ＝0.001). Multivariate analysis revealed high NLR was an independent unfavourable prognostic factor for PFS (hazard ratio [HR] = 1.857, 95% confidence interval [CI] = 1.093-3.154; P = 0.022) and OS (HR = 2.267, 95% CI = 1.221-4.207; P = 0.009). For the patients with high pre-treatment NLR level, ICIs outcome was stratified more clearly by first 3 weeks post- treatment NLR level. Conclusions: The pre- and first 3 weeks post- treatment serum NLR level could be considered as a predictive factor of treatment response for ICIs in patients with advanced HCC.
Association of gut microbiota and metabolites with tumor response to immune checkpoint inhibitors in patients with unresectable hepatocellular carcinoma.
Authors: Lee Pei-Chang , Wu Chi-Jung , Hung Ya-Wen , Lee Chieh-Ju , Chao Yee , Hou Ming-Chih , Kuo Yu-Lun , Chou Shih-Hsuan , Huang Yi-Hsiang
Published: June 2021

e16165

Background: Immunotherapy with checkpoint inhibitors (ICI) is a promising treatment for unresectable hepatocellular carcinoma (HCC), but lack of effective biomarker to predict treatment response. Gut microbiome could modulate tumor response to immunotherapy in melanoma; but its effects on HCC are still unclear. Methods: From May 2018 to April 2020, 94 patients received ICI treatment for unresectable HCC (uHCC) in Taipei Veterans General Hospital, the feces samples were prospectively collected before ICI treatment. Finally, 20 patients with radiology proven objective tumor responses (OR; 3 complete responses and 17 partial responses) following immunotherapy, and 21 randomly selected patients with progressive disease (PD) were enrolled for fecal microbiota and metabolites investigation. In addition, feces from 17 healthy volunteers were taken as normal control. Results: Although the alpha diversity was not significantly different among groups, the principal component analysis of Bray-Curtis distance showed a significant clustering of fecal microbiota between HCC patients and healthy volunteers. The significant bacterial dissimilarity was observed between OR and PD patients following immunotherapy (p = 0.016 and 0.019 by Anoism and Adonis tests, respectively). According to linear discriminant analysis (LDA) effect size (LEfSe), a prominence of Prevotella usually regarded as a pathogenic bacterium, was more abundant in HCC patients with PD to ICI treatment. While Veillonella, Lachnospiraceae, Lachnoclostridium, Lactobacillales, Streptococcaceae and Ruminococcaceae were predominant in patients with OR (LDA score [log10] > 3). In addition, primary bile acids, including murocholic acid, α and β-muricholic acids, and secondary bile acids, including ursodeoxycholic acid, ursocholic acid, tauro-ursodeoxycholic acid, and taurohyocholic acid were significantly dominant in the feces of patients with OR to ICI treatment. Correlation network analysis in patients with OR showed significant linkages between Lachnoclostridium, Ruminococcus and secondary bile acids. Conclusions: Fecal microbiota and bile acids are associated with the response to immunotherapy for uHCC patients. These findings highlight the potential role of microbiota as a biomarker and strategy to enhance response to immunotherapy by modifying gut microbiota for uHCC.
The efficacy and safety of lenvatinib for advanced hepatocellular carcinoma in China: A retrospective, real-world study.
Authors: Yang Xin-Rong , Guo De-Zhen , Chen Fei-Yu , Fan Jia , Jian Zhou
Published: June 2021

e16182

Background: Hepatocellular carcinoma (HCC) is one of the most common malignancy with dismal outcomes. Recently, lenvatinib have been approved as the first-line therapy for unresectable HCC. However, the efficacy and safety of lenvatinib with the combination of other therapy such as transarterial chemoembolization (TACE) and immune checkpoint inhibitor (ICI) therapy was still unclear. Methods: A multicenter retrospective study was conducted and 158 HCC patients treated with lenvatinib from four medical centers were enrolled between November 2018 and December 2020. According to the treatment combined with lenvatinib, all patients were classified into four groups, including lenvatinib monotherapy (LEN) group, combined ICI (c-ICI) group, combined TACE (c-TACE) group and combined ICI and TACE (c-ICI-TACE) group. Objective response rate (ORR) and disease control rate (DCR) were assessed. Overall survival (OS) and time to progression (TTP) were calculated and compared among different groups. Results: All patients (n = 158) were classified into LEN group (n = 40), c-ICI group (n = 42), c-TACE group (n = 39) and c-TACE-ICI group (n = 37). In all patients, the ORR and DCR was 29.1% and 74.1%. The median OS and TTP were 21.8 and 6.2 months, respectively. Four groups showed significant differences in ORR and DCR rates. Specifically, c-ICI-TACE group have significantly higher ORR and DCR rate compared with LEN group (ORR: 12% vs. 38%, P = 0.002; DCR: 60% vs. 89%, P = 0.004). Kaplan-Meier analysis identified that LEN group, c-ICI group, c-TACE group and c-TACE-ICI group showed significantly different TTP (median TTP: 5.0 vs. 6.6 vs. 4.9 vs. 9.5 months; P = 0.021), but similar OS (median OS: 21.8 vs. 19.6 vs. 17.5 months vs. unreached; P = 0.180). Further investigation revealed lenvatinib combined with ICI could prolong TTP compare with lenvatinib without ICI (median TTP: 8.4 vs. 5.0 months; P = 0.019), but it had no significant impact on OS (median OS: unreached vs. 20.1 months; P = 0.300). c-ICI-TACE group showed both better TTP and improved OS compared with other three groups (median TTP: 9.5 vs. 5.2 months; P = 0.004; median OS: unreached vs. 20.1 months; P = 0.034). Univariate and multivariate analysis confirmed that c-ICI-TACE was an independent protective factor for OS (hazard ratio: 0.226; 95% confidence interval: 0.10-0.50; P < 0.001) and TTP (hazard ratio: 0.55; 95% confidence interval: 0.32-0.95; P = 0.032). Most patients (152/158, 96.2%) showed adverse events (AEs) during lenvatinib treatment and the grade 3 AE occurred in 45 patients (28.5%). No significant difference of AE (P = 0.569) and grade 3 AE (P = 0.572) was found among four groups. Conclusions: Lenvatinib was an effective treatment for patients with HCC. Lenvatinib combined ICI could prolong the TTP, while lenvatinib combined ICI and TACE could improve both TTP and OS. Combined therapy wouldn’t escalate the AE and grade 3 AE rates.
Healthcare utilization and outcomes in HIV versus non-HIV patients with hepatocellular cancer: A nationwide analysis.
Authors: Asotibe Jennifer C , Achebe Ikechukwu , Sherazi Syed Ali Amir , Warraich Muhammad-Sheharyar , Attar Bashar , Gupta Shweta , Mullane Michael Russell
Published: June 2021

e16189

Background: Hepatocellular Carcinoma (HCC) remains a leading cause of cancer related mortality and has a 5-year survival after diagnosis of under 20%. HIV-HCC patients are reported to present with advanced disease and shorter survival compared to non-HIV-HCC patients. HIV has not been known to have a direct causal relationship with HCC but chronic immunosuppression, direct effects of HIV virus on liver parenchyma and use of hepatotoxic antiretroviral medications are thought to contribute to the pathogenesis of HCC (Curr Opin HIV AIDS 2017;12:20-25). We studied differences in outcomes and healthcare utilization between HIV and non-HIV-HCC from a national database. Methods: Healthcare Cost Utilization Project (HCUP) National Inpatient Sample (NIS) database was queried to identify all HIV and non-HIV HCC admissions between 2016-2018. The groups were compared for socio-demographic differences, inpatient mortality, length of stay (LOS) and total hospital charges (THC). Secondary outcomes studied were rates of acute kidney injury (AKI), encephalopathy, anemia, upper GI Bleed (LGIB), tumor lysis (TLS), portal hypertension (PH), sepsis, septic shock (SS), neutropenia and protein energy malnutrition (PEM). Statistics were performed using the t-test, univariate and multivariate logistic regression. Results: A total of 845 HIV-HCC and 88,805 non-HIV-HCC inpatient admissions were identified. Compared to non-HIV-HCC, HIV-HCC patients were significantly younger (mean age 59.3 vs 64.7 years, p < 0.0001) with fewer over 65 years old (21.9 % vs 47.4%, p < 0.0001), more males (87.6% vs 74.3%, p < 0.0002) and African American (AA) (44.8% VS 15.9%, p < 0.0001). HIV-HCC cohort were more likely to be treated at a teaching hospital (89% vs 81%, p < 0.035) and had higher comorbidity burden as defined by a high Charlson comorbidity index (p < 0.01) compared to non-HIV-HCC. Odds of adjusted inpatient mortality (aOR= 0.47, CI = 0.27–0.82, p = 0.007) was significantly lower in HIV-HCC with similar LOS (6.5 vs 6.1 days, p = NS) and THC ($85,930 vs $84,592, p = NS) compared to non-HIV-HCC. While rates of neutropenia (2.96% vs 0.62%, p < 0.001) and PEM (26.0% vs 16.3%, p = 0.01) were higher in HIV-HCC, rates of other secondary outcomes were similar compared to non-HIV cohort. Conclusions: HIV-HCC patients are younger, AA, and men with significantly lower inpatient mortality and similar healthcare utilization compared to non-HIV-HCC, despite higher rates of PEM and neutropenia, possibly reflecting advancements in HIV-HCC treatment, and contributed to by younger age and treatment at teaching hospitals. Further studies are needed to evaluate and assess the effect of co-infection with hepatitis on HIV-HCC outcomes which was not evaluated in present study and investigate interventions aimed to reduce complications like PEM and neutropenia to further improve outcomes.
Real-world efficacy and safety of lenvatinib-base therapy for patients with unresectable hepatocellular carcinoma in China: A multicenter retrospective analysis.
Authors: Mai Qicong , Chen Song , Shi Feng , Mo Zhiqiang , He Jian , Guo Wenbo , Chen Xiaoming
Published: June 2021

e16192

Background: Lenvatinib has been approved as a first-line systemic for advanced hepatocellular carcinoma (HCC) after the randomized phase III REFLECT trial. The aim of this study was to assess the lenvatinib-base treatment patterns and safety in real-world clinical settings in China. Methods: In this multicenter retrospective study, A total of 278 patients with unresectable HCC were treated with lenvatinib-base treatment between October 2018 and November 2020 were analyzed. Therapeutic effect was determined using the RECIST 1.1 and mRECIST criteria. Progression free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAE) were also evaluated. Results: Of 278 unresectable HCC patients (median age: 56.1±11.9 years), 220 (79.1%) had cirrhosis caused by HBV infection. 215 (77.3%) and 63 (22.7%) patients were classified as Child-pugh A and B class, respectively. 233 (83.8%) and 45 (16.2%) patients received lenvatinib in first-line and second-line systemic therapies, respectively. 223 (80.2%) patients were treated with lenvatinib plus arterially directed therapy (TACE or HAIC of FOLFOX) and 55 (19.8%) were treated with lenvatinib alone. The objective response rate were 34.9% (RECIST) and 47.5% (mRECIST), while the disease control rate were 75.5%. With a median follow-up period of 12.8 months, the median PFS and OS were 7.8 months (95% CI 7.1–8.4) and 17.2 months (95% CI 14.9–19.6), respectively. Results from the multivariate analysis showed that the significant independent favorable prognosis factors were tumor burden< 50% (P=0.033), Child–Pugh A class (P<0.01), AFP level <200ng/mL (P=0.045), the combination with lenvatinib and arterially directed therapy (P<0.01). TRAE occurred in 219 of 278 patients (78.8%), most common TRAE were hypertension (n=118; 42.4%) and hand-foot skin reaction (n=91; 32.7%). The most common grade 3–4 TARE were hypertension (n=23; 8.3%), decreased appetite (n=18; 6.5%), AST elevation (n=14; 5%), and diarrhea (n=14; 5%) across all study patients. Conclusions: In this multicenter real-world study, lenvatinib-base treatment could be accomplished with well tolerated and response for unresectable HCC patients. Combination with arterially directed therapy could likely improve the overall survival.
Predictors of 30-day readmission rate after liver transplant in patients with hepatocellular carcinoma.
Authors: Salazar Miguel , Upadhyay Banskota Shristi Upadhyay , Acevedo Lou Anne , Palacios Pedro , Gauto Estefania , Baral Binav , Shrivastava Trilok , Khanal Nabin
Published: June 2021

e16193

Background: Liver transplantation (LT) is curative for hepatocellular carcinoma (HCC) in patients within the Milan criteria. Readmissions are common postoperatively, and can be associated with increased morbidity and healthcare burden. Hence we aim to identify incidence, impact and independent predictors for readmission in patients who underwent LT in HCC. Methods: Retrospective study of the 2017 National Readmission Database (NRD) of adult patients readmitted within 30 days after an index admission for LT with an underlying diagnosis of HCC, in patients with cirrhosis we used the BAVENO score to categorize between compensated and decompensated cirrhosis. We aim to identify 30-day readmission rate, mortality, healthcare related utilization resources and independent predictors of readmission. Results: A total of 2,092 patients with HCC underwent liver transplantation. The 30-day readmission rate was 25.6%. Main causes for readmission were post-surgical complications from LT, sepsis, liver failure. Readmitted patients were less likely to have private insurance (40.5% vs 34.5%; P<0.01), to be obese (18.2% vs 7.9%; P<0.01), hypertensive (51.2% vs 39.5%; P<0.01), have history of non-alcoholic steatohepatitis (16.5% vs 2.3%; P<0.01). Readmission was associated with higher in-hospital mortality rate (0.1% vs. 1.5%; P<0.01). The total health care in-hospital economic burden of readmission was $56.1 million in total charges and $15.2 million in total costs. Independent predictors of readmission were type 2 diabetes, transfusion of blood products during index admission, protein-caloric malnutrition, sepsis, and preventive factors were younger age, private insurance and cannabis use. Conclusions: Readmissions after LT in HCC are associated with higher mortality and pose a high health care burden. We identified risk factors that can be targeted to decrease overall patient morbidity, mortality and health care burden.[Table: see text]
Long-term survival and toxicity in patients with progressive advanced neuroendocrine tumors treated with lutetium peptide radiolabelled radiotherapy: A Western Australian long-term follow-up study.
Authors: Kennedy Kim Robyn , Claringbold Phillip , Macdonald William , Boardman Glenn , Ransom David Turner , Turner Harvey
Published: June 2021

e16202

Background: There are limited treatment options for advanced neuroendocrine tumours, and radiolabelled somatostatin analogues have shown favourable safety and efficacy over other existing treatments. Lutetium Octreotate has been shown to be the somatostatin analogue of choice in Peptide Radiolabelled Radiotherapy (PRRT) for advanced neuroendocrine tumours (NETs). Methods: We conducted a retrospective review of the long term safety and survival outcomes of 104 patients prospectively treated on the CLEMENT1, CLEMENT2, NETTLE, and NETT VALuE trials where patients with advanced progressive NETs were treated with Lutetium Octreotate PRRT in Perth, Western Australia. With a median follow-up time of 68 months, this is the longest follow-up study of advanced NETs treated with Lutetium PRRT in the literature to date. Results: Results showed comparable periods of disease stability as other studies, with median progression free survival of 43 months, and superior survival to other series, with a median survival of 71 months. There were patients who had very durable responses, with five year overall survival 61.5%, five year progression free survival 30.1%, 10 year overall survival 30.1%, and 10 year progression free survival of 29.3%, demonstrating Lu 177 can provide a very long duration of response in some patients. PRRT treatment was well tolerated with 1.9% of patients suffering long term renal impairment, and 1% with long term mild thrombocytopenia attributed to PRRT. Importantly, there was a higher rate of MDS and leukaemia in our series (6.7%), which is likely attributed to the longer period of follow-up with all except one case occurring 48 months after PRRT treatment, which is later than the median follow up in most other studies. Conclusions: Overall, this study showed that Lutetium PRRT remains an efficacious and well tolerated treatment in long term follow-up. For clinicians deciding on the timing of PRRT for individual patients the 6.7% long term risk of MDS/leukaemia needs to be balanced against the 29.3% PFS at 10 years. Clinical trial information: ACTRN12610000440022.
Incidence and patterns of secondary malignancies in patients with neuroendocrine neoplasms: A SEER database analysis.
Authors: Sadaps Meena , Mehta Neal , Li Hong , Estfan Bassam N.
Published: June 2021

e16208

Background: Neuroendocrine neoplasms (NENs) are a group of biologically and clinically heterogenous malignancies of different anatomic sites, the majority of which lie within the gastrointestinal (GI) tract. Prior literature has reported on the association between NENs and other primary malignancies (OPM), but these studies are limited by small sample sizes. We aim to further analyze the association of NENs and OPM on a larger scale using a population-based cancer registry. Methods: Primary malignancies with NEN features were identified from the Surveillance Epidemiology and Ends Results registry between 1975-2017. The histology/behavior of NEN included carcinoid tumor, neuroendocrine carcinoma (NEC), pancreatic endocrine tumor, atypical carcinoid tumor, and other (insulinoma, glucagonoma, gastrinoma, VIPoma, somatostatinoma and enterochromaffin cell carcinoid). First NEN observation from each patient was examined. Patients with NEN were grouped into 3 categories: NEN only, NEN first followed by OPM, and non-NEN first followed by NEN based on sequence number of primary cancer. Secondary malignancy sites were analyzed. Distribution of NEN between GI and non-GI sites was described. Demographics were compared by NEN sequence groups and between GI and non-GI sites. Results: 45,896 patients with NEN were analyzed (77.9% Caucasian, 47.0% male, median age 62.0 yrs). 65.7% of NENs were observed in GI sites. Within the GI tract, 31.3% were small intestine, 25.1% rectum, 16.6% pancreatobiliary, and < 11% in other GI locations. Age at NEN diagnosis was younger in those with GI NENs (median 60.0 vs 65.0, p < 0.001). 71.2% of patients had NEN only, 10.4% had NEN first followed by OPM, and 18.4% had a non-NEN primary followed by NEN. Mean age was 58.9 for NEN primary only, 61.0 for NEN primary first and 68.3 for non-NEN primary first (p < 0.0001). More Caucasian patients had non-NEN primary first (82.3%) compared to NEN primary only (76.9%) and NEN primary first (75.5%). There were no gender differences amongst the three groups. Carcinoid tumor histology was more prevalent in NEN primary first (78.6%) compared to NEN primary only (67.3%) and non-NEN primary first (66.6%), while NEC histology was more prevalent in NEN only (27.4%) and non-NEN first (29.3%) compared to NEN first. Among patients with NEN first followed by a second primary malignancy (SPM), 23.6% of females had a secondary breast malignancy and 28.9% of males had a secondary prostate malignancy. Conclusions: 28.8% of patients with NENs were found to have OPM, either preceding or following their NEN diagnosis. Of those with a SPM following NEN, breast and prostate were the most common sites for women and men, respectively. It is imperative that patients with NEN undergo age-appropriate cancer screening to help identify any concurrent malignancies. Further research is warranted to identify the timeframe in which they occur in relation to the NEN.
Real-world neo-adjuvant with or without adjuvant treatment patterns among pancreatic ductal adenocarcinoma patients in the U.S.
Authors: Navaratnam Prakash , Chase Monica , Friedman Howard Steven , Joo Seongjung , Pishvaian Michael J.
Published: June 2021

e16217

Background: The vast majority of pancreatic ductal adenocarcinoma (PDAC) patients have unresectable disease at diagnosis, with only about 20% presenting with either resectable or borderline resectable tumors and who may receive adjuvant with or without neo-adjuvant treatment with surgery. This study seeks to characterize these treatment patterns in the real-world setting. Methods: This was a retrospective observational study to evaluate adjuvant treatment of PDAC patients, with or without neo-adjuvant treatment in the U.S. Patients with at least two medical claims with a primary diagnosis for PDAC between 2016 to 2019 were identified in the Truven MarketScan administrative claims database. A surgical resection within 3 months of any primary PDAC coded medical encounter was the index event, with patients required to be continuously enrolled for at least 3 months before and 6 months after the surgery. Patient demographics and treatment patterns (chemotherapy, radiotherapy, and chemoradiation) were evaluated over the pre-index (3 months) and post-index (3 and 6 months) observation windows. Neo-adjuvant and adjuvant treatment patterns were reported for the overall population and also stratified by age and sex. Results: 737 patients met the selection criteria with a majority (n=520, 71%) being <65 years old and 53% females (n=387). 65% (n=478) of patients received adjuvant chemotherapy during the 6-month post-index compared with 28% (n=207) receiving neo-adjuvant treatment. In the neo-adjuvant setting, patients were likely to receive leucovorin+fluorouracil+irinotecan+oxaliplatin (FOLFIRINOX; 43%, n=88) followed by gemcitabine+pacitaxel (18%, n=37), across all patients, as well as stratified by age or sex. Among patients that received adjuvant but did not receive neo-adjuvant treatment, patients were likely to receive gemcitabine monotherapy (35%, n=112) followed by gemcitabine+capecitabine (GEMCAP; 23%, n=72). Among adjuvant patients that had received neo-adjuvant treatment, the most common chemotherapy regimens were gemcitabine monotherapy (22%, n=35), GEMCAP (18%, n=29) and FOLFIRINOX (16%, n=26). For patients ≥ 65 years old, the most common adjuvant regimen was gemcitabine monotherapy (n=62, 29%) whereas for patients <65, the most common regimens were GEMCAP (25%, n=90) and gemcitabine monotherapy (16%, n=85). Gemcitabine monotherapy (41%; n=118 of 453) was the main adjuvant regimen for patients with index dates of 2016-2017 but for those with index dates of 2018-2019 the most common was FOLFIRINOX (34%; n=64 of 284) followed by GEMCAP (18%; n=35 of 284). Conclusions: The majority (70%) of patients that underwent PDAC resection surgery did not receive neo-adjuvant treatment and about a third of patients did not receive any adjuvant treatment. These results suggest an unmet need in the management of PDAC.
Adjuvant therapy in patients with resected pancreatic adenocarcinoma: Analysis of treatment patterns in a Canadian provincial institution.
Authors: Chahal Manik , Lim Howard John , Davies Janine Marie , Loree Jonathan M. , Renouf Daniel John , Gill Sharlene
Published: June 2021

e16236

Background: In recent years adjuvant therapy (AT) options for pancreatic cancer have evolved. Compared to gemcitabine (Gem) alone, improved overall survival (OS) was demonstrated first in 2017 with gemcitabine and capecitabine (GemCap), and then further improved in 2018 with FOLFIRINOX. Given these options, we retrospectively reviewed the patterns of AT use in British Columbia (BC), Canada during these periods of availability of newer AT regimens. Methods: Patients (pts) treated at BC cancer centers between January 2017 to June 2018 (“GemCap era”), and July 2018 to December 2019 (“FOLFIRINOX era”), who had undergone curative intent resection and received at least one cycle of AT were included for chart review. Patient and disease characteristics, treatment details, and stated rationale for choice of AT regimen were collected. Analyses were performed with one-way ANOVA for comparison of means between regimens, and Chi-squared or Fisher Exact tests to determine correlation between clinicopathologic factors and likelihood of undergoing a given AT regimen. Results: 148 pts were identified: 67 treated in the GemCap era (Gem: 25, 37%, and GemCap: 42, 63%) and 81 treated in the FOLFIRINOX era (Gem: 26, 32%, GemCap: 20, 25%, FOLFIRINOX: 35, 43%). Examined variables included age, gender, ECOG, T and N stage, margins, lymphovascular invasion and post-operative CA19-9. In the GemCap era, use of GemCap vs. Gem was associated with younger average age (p = 0.001) and positive lymph node status (91% vs. 60%, p = 0.003). In the FOLFIRINOX era, use of Gem AT was associated with a delayed time from surgery to treatment (p = 0.045). AT assignment was not influenced by high volume vs low volume centre in the GemCap era. However, when not assigned treatment with FOLFIRINOX in the FOLFIRINOX era, pts were more likely to receive GemCap in low-volume centers, and more likely to recieve Gem in high-volume centers (p = 0.026). The most common stated reasons for choice of an inferior AT regimen were pt comorbidities or functional status (GemCap era: 24% and FOLFIRINOX era: 35%). In total, 40% of patients treated with GemCap and 49% of patients treated with FOLFIRINOX did not complete the intended treatment, with regimen-specific toxicity accounting for 32% (GemCap) and 29% (FOLFIRINOX) of incomplete treatment. Conclusions: With improvements in survival with newer AT regimens, the majority of pts in our real-world setting were assigned the more efficacious AT regimen. Within the limits of a small sample size, significant pt or disease factors predictive of AT assignment were not identified aside from age and lymph node positivity in the GemCap era, and time from surgery to treatment in the FOLFIRINOX era. However, many pts were not able to complete planned AT due to toxicity. Efforts to optimize pt eligibility to improve FOLFIRINOX tolerability are warranted.
Improving outcomes and shared decisions in pancreatic cancer using animated pancreas patient (APP) visual formats of learning: A National Pancreas Foundation (NPF) patient education initiative.
Authors: Munigala Satish , O'Reilly Eileen Mary , Alsante Matthew , Holt Jane , Ko Andrew H. , Gelrud Andres
Published: June 2021

e16242

Background: Pancreatic cancer (PC) outcomes continue to be dismal in the United States (US) and worldwide. Efforts are focused on early diagnosis, treatment, and prevention. However, knowledge translation in PC and effective resources that address patient-provider collaborative decisions are limited and barriers to health literacy continue to impede patient understanding. Evidence increasingly supports the need for informative education for patients to facilitate shared decisions in critical cancer interventions. We evaluated the National Pancreas Foundation’s APP, a visual approach to learning, to determine how shared-decision making and patient barriers to health literacy can be improved, leading to better patient-provider decisions and outcomes. Methods: Using visual formats of learning (animations, videos, and slide shows), we monitored APP website and YouTube metrics from September 2013 to February 2021. We evaluated learner activity, number of views with highest retention in US and globally. Results: APP gathered 4,551,079 views (489,091 views on the APP website and 4,061,988 views on YouTube) from over 100 countries. The majority of viewers (60%) were from the US with 54% being patients, 17% family/caregivers, 16% healthcare providers and 13% other. The animations "Understanding Clinical Trials", "Pancreatic Cancer: Treatment and Outcomes", “Pancreatic Cancer: Signs, Symptoms and Risk Factors", and "Pancreatic Cancer: Pathophysiology, Diagnosis and Staging" had 1,372; 4,643; 8,819 and 4,359 views respectively on the website and 180,845; 77,942; 56,151 and 23,112 views respectively on YouTube. Top expert videos viewed most were "What are the different stages of pancreatic cancer?", "What are the symptoms of pancreatic cancer?", “What is a “Placebo” in a clinical trial and is it always used?”, and “What should I expect following surgery to remove a malignant pancreatic cancer tumor?" with 488; 1,558; 76 and 239 views respectively on the website and 14,869; 10,917; 5,206 and 3,624 views respectively on YouTube. Conclusions: Our study suggests visual formats of education are effective in communicating complex health information to persons with poor health literacy. Pancreatic cancer education based on visual formats have vast potential to provide effective learning for patients. Continued efforts should be made to provide resources for patient-provider shared decisions and address patient health literacy barriers for best health outcomes.
Surgical outcomes and rate of pathological response in resectable/borderline resectable pancreatic cancer patients undergoing neoadjuvant gemcitabine/nab-paclitaxel versus FOLFIRINOX: A retrospective institutional analysis.
Authors: Attah Abraham Attah , Rizwan Saleha , Alhamad Khaled , Turk Micheal , Asawa Palash , Shankar Karthik , Alnimer Lynna , Srinivasamaharaj Srividya , Samhouri Yazan , Monga Dulabh K.
Published: June 2021

e16247

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal solid tumors, predicted to become the second leading cause of cancer related death in some regions of the world. It often presents at an advanced stage, which contributes to poor five-year survival rates of 2%-9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Only about 20% of the cases are diagnosed early enough to undergo surgical resection leading to complete remission. While chemotherapy has an established role in the setting of metastatic disease, utilizing it in the neo-adjuvant setting has been adopted by most institutes for resectable/ borderline resectable cases. Ongoing trials are exploring the use of different regimens in the neo-adjuvant setting. The aim of our study was to identify patients with resectable/borderline resectable PDAC undergoing neoadjuvant chemotherapy and differences in surgical outcome based on the regimen received i.e gemcitabine/ nab-Paclitaxel vs FOLFIRINOX. Methods: A retrospective review was conducted of all patients diagnosed with PDAC from 2017-2019 at Allegheny General Hospital. Data analysis was completed using IBM SPSS v23. Summary statistics were presented using percentages for categorical variables and medians with interquartile ranges for continuous variables. Results: Out of 121 patients who received and completed treatment in our institution, 30 underwent neoadjuvant chemotherapy treatment followed by surgical intervention. 21 (70%) patients were found to be borderline resectable, 8 (27%) patients were resectable and 1 patient had locally advanced PDAC. 16 (53%) patients received FOLFIRINOX compared to 13 (43%) patients received gem/nab-paclitaxel. Among patients who received neoadjuvant FOLFIRINOX, 5 out of 16 (31%) patients had moderate to significant treatment response at the time of surgery compared to 7 out of 13 (54%) patients who received gemcitabine/nab-paclitaxel. Conclusions: Our study revealed no significant difference (p=0.21) between the patients who received neoadjuvant gemcitabine/nab-paclitaxel vs FOLFIRINOX in terms of treatment response assessed pathologically at the time surgical resection. We recognize the limitations of our study in terms of it being a retrospective analysis with a small sample size and therefore further prospective and randomized controlled trials are needed to determine the most suitable and effective regimen in the neoadjuvant setting for resectable/borderline resectable PDAC patients. Response to treatment among different chemotherapy groups.[Table: see text]
Assessment of compliance with national guidelines in genetic testing and tumor profiling in patients diagnosed with pancreatic adenocarcinoma: A retrospective review.
Authors: Shankar Karthik , Srinivasamaharaj Srividya , Samhouri Yazan , Rizwan Saleha , Shah Deep , Liu Jiaxiang , Helfand Alexander M , Patibandla Naga Sai Krishna , Miller Katherine , Kancharla Pragnan , Khattab Ahmed , White Richard , Bakalov Veli , Monga Dulabh K.
Published: June 2021

e16260

Background: Pancreatic ductal adenocarcinoma (PDAC) remains one of poor prognosis, portending a 5-year survival rate of 9% when considering all stages. Although the mainstay of treatment of PDAC remains cytotoxic chemotherapy in both the early and advanced stages, recent advances in tumor profiling and germline testing have allowed for the incorporation of poly-ADP-ribose polymerase (PARP) inhibitors, immune checkpoint inhibitors and targeted therapy to be utilized in the maintenance and subsequent-line settings for metastatic PDAC, respectively. We sought to identify our institutional compliance rate in germline testing and tumor profiling in all patients diagnosed with PDAC. Methods: A retrospective review was conducted of all patients diagnosed with PDAC from 2017-2019 at Allegheny General Hospital. Data analysis was completed using IBM SPSS v23. Summary statistics were presented using percentages for categorical variables and medians with interquartile ranges for continuous variables. Results: Out of 171 patients reviewed, 121 received and completed treatment in our institution, and were included in the analysis. Median age was 69 years. 55 patients (45%) were male and 66 (55%) were female. Germline testing was done in 28 patients (23%) and tumor molecular profiling was done in 25 patients (21%). Testing for microsatellite instability was performed in 28 patients (23%). Testing for programmed death-ligand (PD-L1) expression was done in 16 patients (13%). On univariate analysis, family history of malignancy was a predictor for germline testing (OR 5.3; 95% CI 1.4-2.01; p=0.01). No predictors were identified in association with tumor molecular profiling likely due to low sample size. Conclusions: Our analysis reveals an institutional compliance rate of 20-23% in adherence to national guidelines with respect to germline testing and tumor profiling in the management of PDAC. A family history of malignancy demonstrated predictive association with germline testing. Factors which may limit pathological evaluation of microsatellite stability status, assessment of PD-L1 expression and molecular profiling include lack of institutional protocol for reflex histological testing, financial or insurance constraints, and lack of adequate tissue. As part of our Quality improvement project, we identified that incorporation of reflex histological testing based on tumor-type, standardization of tissue biopsy to optimize yield, and utilization of support staff, such as Oncology Navigators, to facilitate scheduling for germline testing may increase compliance rates.
Updated single institution outcome data from the first-in-human CEND-1 trial in metastatic pancreatic cancer.
Authors: Dean Andrew Peter , Mulligan Fiona , Kelly Geena , Shaughnessy Emma , Wilson Kate
Published: June 2021

e16274

Background: In our phase I trial of the first-in-class agent CEND-1 with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer, we reported a preliminary overall RR of 59% in 29 patients across 3 institutions. Our site enrolled 19 of these patients and we present updated outcome data from this institution. CEND-1 is a bifunctional cyclic peptide (a.k.a. iRGD) that homes to tumors via RGD motif interaction with alphav-integrins and then transforms the solid tumor microenvironment into a temporary drug conduit via interaction with neuropilin-1. This leads to an enhanced tumor delivery of co-administered anti-cancer agents. Methods: We reviewed our updated outcome data from the first in human CEND-1 trial in pancreatic cancer. Patients received a combination of CEND-1 with nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) on days 1, 8, 15 of a 21-day treatment cycle. Data was analysed to determine response rate, progression free survival and ongoing benefit. Results: Of the 19 patients that were enrolled at this institution; 13 (69%) showed partial response, 5 (26) % had stable disease, and 1 (3.4%) had progressive disease. Median progression free survival for this cohort was 8.8 months. 4 patients (21%) remain on the trial without disease progression to date. Median treatment duration for these patients is 20 months (range 17.1 – 24.6 months). Adverse events were as previously described¹ with no new significant events or toxicities. Conclusions: Ongoing follow-up data from the CEND-1 study at our institution shows ongoing continuing benefit for patients who remain on trial with notable progression free survival. No new safety signals or adverse events have been detected with this prolonged follow-up. The randomised phase 2 trial of this combination will be proceeding later this year. Clinical trial information: ACTRN12618000804280.
Frequency and risk factors for metastasis in newly diagnosed appendiceal carcinoma.
Authors: Minhas Ahmed , Minhas Sohail A.
Published: June 2021

e16281

Background: Appendiceal carcinoma has an insidious clinical presentation, and these tumors are rarely suspected prior to surgery, potentially leading to late diagnosis. The aim of this study is to investigate the prevalence of metastatic disease at initial presentation and potentially associated sociodemographic characteristics. Methods: Patients were identified from the Surveillance, Epidemiology, and End Results (SEER) program using ICD-O-3 histology/behavior codes between 2010-2015. Logistic regression was performed to determine the association of metastasis at presentation with tumor subtype, adjusted for age, race, sex, insurance and marital status, grade, and tumor and nodal stage using the seventh edition of the American Joint Committee on Cancer (AJCC) staging system. Results: We identified a total of 3, 447 patients with known metastatic status. 38.4% had metastatic disease at diagnosis. Compared to colonic-type adenocarcinoma (CA), mucinous adenocarcinoma (MA) was associated with significantly higher odds of presenting with metastasis at diagnosis in unadjusted (OR 3.55; 95% CI [2.97-4.24]) and adjusted (OR 2.97 [2.26-3.89]) regression. Signet ring cell carcinoma (SC) also had higher odds in unadjusted (OR 3.91 [2.99-5.12]) and adjusted (OR 2.05 [1.33-3.15]) regression. Goblet cell carcinoma (GC) was associated with lower odds in unadjusted (OR 0.28 [0.21-0.37]) and adjusted (OR 0.58 [0.36-0.94]) regression. The table describes the association of tumor and nodal stage with metastasis at diagnosis. Women had higher odds in unadjusted (OR 1.59 [1.39-1.82]) and adjusted (OR 1.93 [1.55-2.39]) regression. 90.1% of CA, 84.2% of GC, 42.2% of MA, and 78.5% of SC patients with metastasis at diagnosis had extraperitoneal distant metastasis (M1b). Conclusions: A significant proportion of patients with appendiceal carcinoma had metastasis at diagnosis. Compared to CA, MA and SC were much more likely to present with metastasis at diagnosis, while GC was less likely. Women had almost twice the odds of presenting with metastatic disease as men. T4 and N2 stages showed much higher odds of metastasis at diagnosis compared to T1 and N0 stages, respectively. Surprisingly, T2 and T3 stages were associated with lower odds of metastasis at diagnosis than T1 stage.[Table: see text]