bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment outcomes for stage T1b-2 esophagogastric adenocarcinomas.
Authors: Diab Maria , Khalil Lana , Goyal Subir , Switchenko Jeffrey M. , Alese Olatunji B. , Akce Mehmet , Wu Christina , El-Rayes Bassel F. , Shaib Walid Labib 
Published: June 2021

e16085 Background: Treatment of localized esophageal, gastroesophageal junction (GEJ), and stomach cancer is neoadjuvant therapy with either chemoradiation or chemotherapy followed by surgery. Treatment for T1b-2 stage disease is not well evaluated and this stage is underrepresented in prospective studies. The aim of this study is to evaluate survival outcomes among the three treatment modalities (neoadjuvant chemotherapy (NACT), neoadjuvant chemoradiation (NACRT), and upfront surgery (US)) in this population using the National Cancer Database (NCDB). Methods: Patients (pts) with clinical stage T1b-2N0 and any pathological stage (excluding metastatic) adenocarcinoma of the esophagus, GEJ, and stomach treated with neoadjuvant therapy or upfront surgery, with or without adjuvant chemotherapy (AC), were identified between 2004 and 2015 in the NCDB. Univariate and multivariable analyses were conducted, and Kaplan-Meier analysis and Cox proportional hazard models were used to identify the association between the three treatment modalities and overall survival (OS). Results: A total of 2260 pts were analyzed. The median follow-up was 66.6 months. The median age was 67 years. Most pts were White (86%) and male (77%). 1018 (45%) had moderately-differentiated grade, while 946 (42%) had poorly-differentiated/undifferentiated grade. The most common site of disease was the lower third of esophagus (34.1%). 161 pts (7%) received NACT, of whom 45 pts received AC; 537 pts (24%) received NACRT, of whom 40 pts received AC. 1562 pts (69%) underwent US, of whom 146 pts received AC. US with AC was associated with the best survival, followed by NACT with AC; median OS was 90.1 and 86.8 months for surgery with AC and NACT with AC, respectively. NACRT was associated with the worst survival (39.5 and 40.2 months with and without AC, respectively). The 5-year OS rates were 59.8%, 58.5%, 52.1%, 44.9%, 37.3%, and 37.8%, for US, NACT, and NACRT, with and without AC, respectively. The rate of tumor upstaging was highest in the NACT group, followed by the NACRT group, and lowest in the US group. Postsurgically, 62 (39%) and 48 (30%) pts in the NACT group and 198 (37%) and 161 (30%) pts in the NACRT group had upstaging in their T and N stages, respectively, compared to 214 (13%) and 326 (21%) pts in the US group. For the 1107 pts who also had pathological T1b-2N0 stage disease following US, no difference in survival was observed with or without AC. Conclusions: Upfront surgery with adjuvant chemotherapy and perioperative chemotherapy are associated with the best survival compared to preoperative radiotherapy. This is the largest study to address the best approach for the treatment of T1b-2 stage disease.
PRIME-HCC: Phase Ib study of neoadjuvant ipilimumab and nivolumab prior to liver resection for hepatocellular carcinoma.
Authors: Pinato David James , Cortellini Alessio , Pai Madhava , Spalding Duncan , Talbot Thomas , Goldin Robert D. , Gupta Aneta , Cole Tom , Ward Caroline , Yip Vincent S. , Dhillon Tony Singh , Slater Sarah , Sodergren Mikael , Tait Paul , Habib Nagy A. , Thomas Robert , Sharma Rohini 
Published: June 2021

e16131 Background: There are no approved peri-operative anti‐cancer therapies for patients with hepatocellular cancer (HCC) who are candidates for liver resection (LR). Combination immunotherapy induces radiologically measurable responses in > 25% of patients with HCC, providing a rationale for neoadjuvant use in surgical candidates. Methods: PRIME‐HCC is a two-part, multi-centre, phase Ib study to assess safety and bioactivity of the nivolumab (3 mg/kg, day 1 and day 22) plus ipilimumab (1mg/kg, day 1 only) combination prior to LR in early-stage HCC. The primary objective of the study is to determine the treatment-related adverse events (trAE) and delays to surgery. Efficacy endpoints include overall response rates (ORR) by RECIST v1.1 and pathologic responses on resection specimens. Results: At the data censoring time of Jan 29th 2021, 7 patients were enrolled, all were of Child-Pugh class A, with cirrhosis (n = 6, 85.7%) secondary to viral etiology (n = 4, 57.2%). Male/female ratio was 6/1 and median age was 66 (range: 57-70). The median diameter of the dominant liver lesion was 3.3 cm (inter quartile range, IQR 1.2, range 1.1-4.1 cm) and the median number of nodules was 2 (IQR 0.5; range 1-3). Study part I (n = 6) was completed with no surgical delays. TrAEs of all grade were observed in 6/7 safety-evaluable patients (85%). TrAEs of grade >2 occurred in 3 patients (42%) and included grade 3 transaminitis (n = 1), grade 2 thyroid toxicity (n = 1), grade 2 infusion reaction (n = 1) and fatigue (n = 1). One patient was diagnosed with cholangiocarcinoma after dosing and was removed from efficacy analyses. ORR according to RECIST v1.1 criteria in efficacy-evaluable patients (n = 5) was 20%, including 1 partial response and 4 disease stabilisations. Pathological responses were observed in 3 out of 5 pathologically evaluable patients (60%). Conclusions: Neoadjuvant immunotherapy with nivolumab plus ipilimumab is tolerable, does not compromise management of patients on a radical pathway of care and is characterised by anti-tumour efficacy in early-stage HCC. Clinical trial information: NCT03682276.
A new staging system for radiotherapy-based treatment of hepatocellular carcinoma: A multicenter cohort study.
Authors: Su Ting-Shi , Liang Shi-Xiong , Li Li-Qing , Liu Qiu-Hua , Zhu Xiao-Fei , Liang Ping 
Published: June 2021

e16155 Background: External beam radiation therapy has been used as a palliative to radical treatment of hepatocellular carcinoma (HCC) depending on different tumor status, liver function and patient's general state of health. The existing models of HCC staging cannot perfectly predict the prognosis of radiotherapy. In this study, we aimed to set up a new staging system for radiotherapy-based treatment by incorporating bilirubin-albumin (ALBI) grade and tumor status for the prognostic classifications of HCC. Methods: This multicenter cohort study included 878 HCC patients who received radiotherapy-based treatment. A new staging system was established: stage I, solitary nodule without macrovascular invasion or 2-3 nodules with no more than 3.0 cm each other and PS 0-2 (Ia: ALBI-1 grade; Ib: ALBI-2 or 3 grade); stage II: 2-3 nodules with anyone more than 3.0 cm or ≥4 nodules and PS 0-2 (IIa: ALBI-1 grade; IIb: ALBI-2 grade); stage III: macrovascular invasion or regional lymph node metastasis or distant metastasis and PS 0-2 (IIIa: ALBI-1 grade; IIIb:ALBI-2 grade); stage IV: ALBI-3 grade without stage I patient or/and PS score 3-4. The new modified staging system and the existing staging systems, such as the BCLC, TNM, CNLC staging systems were used for prognostic analysis. All patients were separated into different stages and substages. The long-term overall survival outcomes and time-dependent receiver operating characteristic (ROC) were analyzed. Results: A training cohort of 595 patients underwent stereotactic body radiotherapy (SBRT) from 2011 to 2017 and an external validation cohort of 283 patients underwent intensity-modulated radiotherapy (IMRT) from 2000 to 2013 were included into establishing and validating the new staging system. In the training cohort, the median follow-up time was 55 months (range, 6–100 months), and the new staging system had a good discriminatory ability to separate patients into different stages with 4 notably different curves and substages with 7 notably different curves. BCLC staging could not differentiate stage 0 to A, and stage C to D in these selected patients. TNM staging could not completely distinguish stage IIIb to IV, but also stage Ia to Ib. CNLC staging could not differentiate among stage IIIa, IIIb, and IV. In the external validation, the median follow-up time was 95 months (range, 9–120 months), and the new staging system also had a good discriminatory ability to separate patients into different stages with 4 notably different curves and substages with 7 notably different curves. The new staging system had a better area under curve of time-dependent ROC than BCLC, TNM and CNLC staging in both SBRT and IMRT cohorts. Conclusions: The new modified (Su’s) staging system could provide a good discriminatory ability to separate patients into different stages and substages after radiotherapy treatment. It may be used to supplement the other HCC staging systems.
Molecular alterations, tumor microenvironment and clinical correlations in Thai cholangiocarcinoma patients.
Authors: Bamrungwong Panuchai , Oranratnachai Songporn , Sornmayura Pattana , Incharoen Pimpin , Iemwimansa Nareenart , Trachu Narumol , Panthan Bhakbhoom , Monnamo Nanamon , Sae-Lim Pakatorn , Charoenyingwattana Angkana , Panvichien Ravat , Sirachainan Ekaphop , Chantratita Wasun , Reungwetwattana Thanyanan 
Published: June 2021

e16176 Background: The systemic treatment option of unresectable and advanced cholangiocarcinoma (CCA) is limited. The mainstay of treatment is gemcitabine and 5-FU based chemotherapy. Recently, there is the role of promising immunotherapy in MSI-HI CCA. This research aims to study molecular alterations and tumor microenvironment in Thai CCA patients in order to explore the novel treatment and the clinical correlations. Methods: Thirty-six CCA patients in Ramathibodi Hospital between year of 2018 and 2020 with adequate tissue were enrolled. NGS by ThermoFisher (comprehensive panel) for molecular profile and immunohistochemistry (IHC) staining for tumor microenvironment protein expression (CD3, CD4, CD8, CD20, CD138, CD163, FOXP3), and PD-L1 were performed. Clinical data was retrieved from electronic medical record. Survival analysis, univariate and multivariate analysis were performed by Cox-regression analysis. Stata version 16.0 was used for statistical analysis. Results: Intrahepatic CCA was the most common type of CCA in our population (81%). The top 10 common mutations were TP53 (69%), KMT2D 58%), KMT2B (52%), ARID1A (50%), FAT1 (50%), NOTCH3 (44%), FANCA (42%), SMAD4 (42%), EPHA2 (39%), and ARID1B (39%). We also found the interesting targetable genes in our CCA patients, such as, KRAS (33%), MTOR (33%), HER2 (31%), EGFR (31%), FGFR2 (28%), BRCA2 (25%), PIK3CA (22%), NTRK1 (19%), BRCA1 (17%), NTRK3 (11%), and BRAF (8%). Three patients had ALK fusion gene, 1 patient had NTRK1 fusion and the other one had NTRK3 fusion gene. Twelve out of 36 patients (33%) had MSI-HI and 56% of patients had TMB ≥ 10 mutations/megabase. The clinical factors significantly correlated with poor overall survival (OS) were unresectable disease, stage IV, bilirubin > 1.2, and CEA ≥ 22.5. The NF1, MTOR, HER2 mutations, and FOXP3-negative in stromal cells were significantly associated with longer OS, whereas EGFR, APC, FGFR2, and BRCA1 mutations might correlated with better OS. Conclusions: Our study demonstrated the unique molecular profile of Thai CCA patients. We found high prevalence of MSI-HI and high TMB in our population, together with the promising potential of targetable genes for developing targeted therapy in the future. FOXP3 expression was probably one of potential predictive biomarker for immunotherapy. Larger cohort should be explored.
Dispersion in total cost of care for Medicare fee-for-service (FFS) patients with metastatic pancreatic cancer receiving FDA-approved/NCCN Category 1 regimens at teaching versus non-teaching institutions.
Authors: Latimer Helen , Tomicki Samantha , Dieguez Gabriela , Cockrum Paul , Kim George P. 
Published: June 2021

e16244 Background: Teaching institutions receive additional funding from Medicare & Medicaid Services (CMS) to provide specialized, quality care. Objectives: To analyze the dispersion in total cost of care (TCOC) for Medicare FFS patients (pts) with metastatic pancreatic cancer (m-PANC) treated at teaching (teach) or non-teaching (non-teach) institutions. Methods: We identified pts with m-PANC using ICD-9/10 diagnosis codes in the 2016-18 Medicare Parts A/B/D 100% Research Identifiable Files. Study pts had 2+ claims with a pancreatic cancer diagnosis and Medicare FFS coverage for 6 months pre- and 3 months post-metastasis diagnosis. Study pts were treated with NCCN Category 1 regimens: 1L gemcitabine monotherapy (gem-mono), 1L gemcitabine/nab-paclitaxel (gem-nab), 1L FOLFIRINOX (FFX), and 2L liposomal irinotecan-based regimen (nal-IRI). Pts were attributed to teach or non-teach institutions based on plurality of chemotherapy claims. TCOC reflects insurer-paid services per line of therapy (LOT) for 3 categories: chemotherapy/supportive drugs (chemo/Rx), inpatient care (IP), and other outpatient care (OP). We grouped pts by quartile (qrt), evaluated drivers of TCOC, and mean rates of admissions (admits/pt). Results: We identified 3,908 (teach) and 2,632 (non-teach) pts taking NCCN Category 1 regimens. There was a similar mix of patients in both cohorts, with gem-mono pts making up only 3% of the sample. Gem-nab accounted for 73% and 70% of pts in teach and non-teach institutions, respectively. For gem-nab, FFX, and nal-IRI pts, median TCOC was similar in both cohorts. However, median TCOC for the two non-generic drugs in our study, gem-nab (teach: $36,332; non-teach: $40,135) and nal-IRI (teach: $31,526; non-teach: $39,360), were lower at teach institutions than non-teach institutions. The components of TCOC are similar between teach and non-teach institutions in all qrts. In both cohorts, % IP costs for all regimens increased between the first and fourth qrt (teach:14% to 23%, non-teach:14% to 26%). In the teach cohort, nal-IRI pts had the lowest admits/pt in all qrts. In the non-teach cohort, there was no discernable pattern, although nal-IRI pts had the lowest admits/pt in the second and fourth qrt. Conclusions: For non-generic regimens like nal-IRI and gem-nab, median TCOC was lower at teach institutions than non-teach institutions. There were no consistent differences in TCOC dispersion or admissions between cohorts. Across qrts, chemotherapy accounted for approximately half the TCOC. However, IP costs were proportionally higher in the fourth qrt, especially for non-teach institutions. Despite nal-IRI pts being on the second LOT, both median TCOC and admits/pt across qrts were lower than gem-nab and FFX in teach institutions. In the non-teach cohort, median TCOC were similar among nal-IRI, gem-nab, and FFX.
Anticoagulation outcomes in patients with venous thromboembolism following Whipple surgery for pancreatic cancer: Single center experience.
Authors: Balanchivadze Nino , Purtell James P , Kuriakose Philip , Clark Julie , Springer Kylie , Divine George , Kwon David S. , Dobrosotskaya Irina Y. 
Published: June 2021

e16255 Background: Venous thromboembolism (VTE) is a common complication in patients with pancreatic cancer (PC). Incidence of major bleeding and clinically relevant non-major bleeding is 14%-20% in patients with cancer who receive anticoagulation therapy (AT). Whipple procedure is a complex surgical intervention offering potential cure in patients with resectable PC; however, surgery can affect drug absorption, which may reduce effectiveness of AT or exacerbate drug related adverse events. Our aim was to assess incidence of bleeding in PC patients who had whipple procedure with subsequent VTE. Methods: Retrospective analysis of medical records for all adult patients with PC who underwent whipple procedure and developed VTE (between July 1, 2010, and July 1, 2020) at Henry Ford Hospital was performed. Multiple variables and outcomes were analyzed by two-group comparisons, univariate analysis, and Cox regression. Results: A total of 32 patients were included in the analysis. The mean (standard deviation [SD]) age was 67.4 (11 y) years, 16 (50%) patients were men, and 16 (50%) were women, (20 [63%] White; 11 [34%] Black; 1 [3%] Asian). The median Khorana score was 3 (range, 2–4). Of the 32 patients, 6 (19%) had upper extremity VTE, 11 (34%) had lower extremity VTE, 10 (31%) had a pulmonary embolism, 7 (22%) had intra-abdominal VTE, and 7 (22%) had recurrent VTE. All patients with upper extremity VTE had a peripherally inserted central catheter (PICC) or a venous port at the time of VTE diagnosis. Most of the patients (28 or 88%) received AT. Whereas 13 (41%) patients had at least one bleeding episode, 19 (59%) had no bleeding. Twenty-two (68%) patients did not need PRBC transfusion, while 4 (13%) patients required > 4 units packed red blood cell transfusion. No significant association between bleeding and AT was observed ( p = .590). Patients with a bleeding event had lower hemoglobin levels ( p = .030) and were more likely to receive blood transfusion ( p = .005). Cox regression analysis did not show patient age, ethnicity, type of AT used, recurrent VTE, and neoadjuvant chemotherapy treatment to be significantly associated with bleeding or death. A total of 14 (44%) patients were alive at the time of analysis. Conclusions: In patients with PC and VTE who received AT after whipple procedure, the incidence of bleeding was higher than what has been reported in patients with cancer in general, regardless of type of AT administration. Patients with central venous catheters might be at increased risk of upper extremity VTE and this subset of patients may benefit from various risk reducing strategies. Caution is recommended while managing AT in this complex patient population, and more studies are needed to assess factors specifically associated with AT and bleeding after whipple procedure.
Humanized anti-DEspR monoclonal antibody to improve overall survival in xenograft pancreatic peritoneal carcinomatosis nude rat model.
Authors: Gromisch Christopher , Gromisch Matthew Stannard , Grinstaff Mark , Herrera Victoria L.M. , Ruiz-Opazo Nelson 
Published: June 2021

e16262 Background: Pancreatic adenocarcinoma (PDAC) with peritoneal carcinomatosis (PPC) has the worst median overall survival (mOS) among all PDAC metastasis. Novel therapeutic approaches are needed for PPC. The Dual Endothelin-1/VEGF-signal-peptide Receptor (DEspR) is a cell surface receptor which regulates PDAC tumor cell and cancer stem-like cell (CSC) anoikis resistance, tumorigenicity, and tumoral angiogenesis. To translate these findings into a novel anti-cancer therapy, we evaluated the efficacy, empirical safety, pharmacokinetics, and pharmacodynamics of a recombinant, humanized, anti-DEspR hinge-stabilized IgG4S228P monoclonal antibody, hu-6g8, in a PPC xenograft tumor nude rat model. Methods: We used a Panc1 CSC-derived xenograft tumor model of PPC developed via intraperitoneal injection of two million Panc1 CSCs functionally isolated for anoikis resistance. Isolated CSCs had variable DEspR expression, thus modeling CSC-heterogeneity. For efficacy studies, PPC-rats were randomized to receive a single intravenous injection of either 3mg/kg or 15mg/kg hu-6g8, 100mg/kg gemcitabine, or saline, given 3 weeks after CSC injection with palpable PPC tumors. Blood samples were collected to monitor for hematological adverse events (AEs) and vital organs were collected to evaluate for hu-6g8-induced apoptosis. Pharmacokinetics was assessed in a separate study cohort by sequential blood draws after rats received a single dose of 3 mg/kg or 15 mg/kg hu-6g8. In a 3rd cohort, pharmacodynamics were assessed by vital organ collection and immunohistochemistry after rats received either a single-iv injection of 3mg/kg hu-6g8 or IgG4 isotype control. Results: Single dose 15 mg/kg hu-6g8 treatment significantly improved median overall survival (189 days, n = 0.0007) with 3 mg/kg hu-6g8 being comparable to 100 mg/kg gemcitabine (92 vs 115 days, n = 0.62). No hematological AEs were observed in hu-6g8 treated rats, and there was no evidence of increased apoptosis by hu-6g8 in normal tissues by immunohistochemistry of activated Caspase-3. Hu-6g8 demonstrated an average elimination half-life of 46.1 hrs in a two-compartment model. Biodistribution of the antibody showed predominant uptake, albeit heterogenous, and induction of activated caspase 3+ apoptosis in the peritoneal tumors by 24-hours with minimal off-target binding. Conclusions: Treatment with monoclonal hu-6g8 significantly improved survival in a model of PCC with excellent tumor specificity and minimal off-target effect.
Detection of FGFR3 alt in plasma cfDNA in metastatic UC patients receiving Erda therapy.
Authors: Sarfaty Michal , Teo Min Yuen , Funt Samuel Aaron , Lee Chung-Han , Aggen David Henry , Ratna Neha , Regazzi Ashley Marie , Lenis Andrew Thomas , Chen Ziyu , Al-Ahmadie Hikmat A. , Brannon Angela Rose , Berger Michael F. , Solit David B. , Rosenberg Jonathan E. , Bajorin Dean F. , Iyer Gopa 
Published: June 2021

e16519 Background: The pan-FGFR inhibitor erdafitinib (erda) is FDA-approved for pretreated mUC pts harboring FGFR2/3 alterations. We explored concordance of FGFR3 alt profiles between primary tumor and cfDNA using the next generation sequencing assay MSK-ACCESS. We also correlated changes in FGFR3 cfDNA mutant allele fraction (MAF) with response to erda. Methods: After consent on an approved biomarker protocol, plasma samples were collected from mUC pts on erda at baseline, on treatment (tx), and at progression along with patient clinical characteristics. Baseline tumors were sequenced with MSK-IMPACT and plasma samples sequenced with MSK-ACCESS, a cfDNA platform that sequences select exons and introns of 129 genes and uses unique molecular indexes to detect somatic mutations down to 0.1% MAF. Results: Between 8/2019-12/2020, 18 pts started erda 8mg daily and had plasma drawn for MSK-ACCESS. Three pts increased to 9mg daily, 7 required dose reductions and 10 had dose interruptions. Treatment was discontinued in 13 pts for disease progression and 3 for toxicity. Median PFS was 3.7 months. FGFR3 S249C was the most frequent alt detected (11/18, 61%), then Y373C (3/18, 16%), and R248C (2/18, 11%) (Table). FGFR3 alt were detected in 15/18 (83%) baseline plasma samples, all of which were of the same alt as tumor tissues. In 3 samples, additional FGFR3 alt were detected, including 1 pt with an FGFR3-TACC3 fusion and hotspot mutations found only in cfDNA. FGFR3 MAF decreased in 7 of 9 pts on erda, 2 of whom declined to undetectable levels. Conclusions: A high degree of concordance of FGFR3 alt was observed between primary tumors and cfDNA. Most erda responders displayed reduction of FGFR3 cfDNA MAF. FGFR3 alts exclusive to cfDNA were found in a small subset of pts. Further pt accrual and follow-up are ongoing to assess for correlations between erda response/progression and changes in FGFR3 cfDNA MAF, and to assess whether cfDNA can identify resistance mechanisms.[Table: see text]