tbuckley/cabot-search huggingface dataset:
Survival outcomes according to the tumor mutation burden and PD-L1 expression in hepatobiliary tumors.
Authors: Jorge Sánchez-García, Fidel Lopez-Verdugo, Andrew Gagnon, Diane Alonso, Shiro Fujita, Manuel Rodriguez-Davalos, Mark Andrew Lewis, David Michael Gill, Richard Gilroy, Derrick S. Haslem, Timothy Joseph Yeatman, Jake Krong, Li Dong, Sean Dow, Ivan R Zendejas-Ruiz, Ramya Thota
Journal: Journal of Clinical Oncology (2020)

566 Background: Hepatobiliary (HB) tumors are aggressive tumors with emerging evidence for increasing sensitivity to immune checkpoint inhibitors (ICI). Tumor mutation burden (TMB) was found to be a quantitative biomarker associated with production of neoantigens within the tumor and predict the sensitivity to immune therapy. Herein, we explore the TMB, microsatellite instability (MSI) and PD-L1 expression as a potential biomarker of response to immune therapy in HB tumors. Methods: We retrospectively assessed all patients with hepatobiliary malignancies who have undergone next generation sequencing (NGS) between October 2009 and June 2019. We then analysed the tumor mutation burden and PD-L1 of these tumors and also identified frequency of patients with no clinically actionable mutations. Results: In our total 61 patients with HB tumors predominantly were male (62.3%) with mean age of 63 years. Thirty-four patients had hepatocellular carcinoma, 22 patients had cholangiocarcinoma and 5 patients had gallbladder carcinoma. The most common risk factors were smoking status, cirrhosis, alcohol consumption and hepatitis C virus. The mean TMB reported was 3.2 (1.16 – 7.35). MSI was identified in 13 patients and one was indeterminate. Only 17 patients had PD-L1 positive. At least, 37 patients had one clinically actionable mutation while 24 patients had no clinically actionable mutations. Mean overall survival was 16.6 months, but no statistically significant difference was found by high PD-L1 (3 vs 3.7 months, p=0.3) expression. Conclusions: Our data suggests the TMB in HB tumors is low in general irrespective of their underlying risk factors. We also noted more than half had microsatellite stable tumors and PD-L1 expression. Future larger studies are needed to evaluate TMB, MSI and PD-L1 as a potential biomarker in hepatobiliary tumors to help select patients that will benefit from immune therapy.
Changes in glucose tolerance after pancreatectomy in patients with pancreatic ductal adenocarcinoma.
Authors: Sachiyo Shirakawa, Hirochika Toyama, Shohei Komatsu, Jun Ishida, Masahiro Kido, Takumi Fukumoto
Journal: Journal of Clinical Oncology (2020)

668 Background: Diabetes mellitus (DM) is reported to be related to pancreatic ductal adenocarcinoma (PDAC). Long-standing DM is a risk factor for PDAC, meanwhile, quite a few patients with PDAC develop DM as a paraneoplastic disorder and some papers reported that DM affected prognosis for PDAC. In this study, we investigated pre- and post-operative glucose tolerance in patients with pancreatectomy for PDAC or other disease. Methods: This single-center prospective study included 69 patients with pancreatectomy (40 pancreaticoduodenectomy (PD) and 29 distal pancreatectomy (DP) ) who received 75-g oral glucose tolerance test (OGTT) and glucagon test pre- and one month postoperatively. Plasma glucose, insulin, and C-peptide (CPR) at 0-, 30-, 60-, and 120-min during OGTT; and 0- and 6-min during glucagon test were obtained. These data and survival outcomes were analyzed. Results: There were 20 (29%) PDAC patients: 12 (30%) in PD group and eight (28%) in DP group. Nine patients with PDAC (45%) and seven patients (18%) without PDAC demonstrated DM type in preoperative OGTT. After pancreatectomy, 11 patients (55%) with PDAC and seven patients (15%) without PDAC experienced improvement in OGTT (P=0.0005). Greater improvement in homeostasis model assessment insulin resistance that were obtained by OGTT and used to measure insulin resistance, was noted after surgery in PDAC patients compared with non-PDAC patients (-1.4 vs -0.5 in PD group, P=0.07; -0.8 vs +0.06 P=0.05 in DP group). Delta CPRs obtained by glucagon test were significantly decreased postoperatively (3.0 to 1.1 ng/mL, P&lt;0.0001 in PD group; 3.3 to 1.8 ng/mL, P&lt;0.0001 in DP group). In survival analysis, fasting plasma glucose &gt;110 mg/dL (HR 3.9, 95%CI 1.5-10, P=0.005) and the average of plasma insulin &gt; 25 µIU/mL during OGTT (HR 0.36, 95%CI 0.14-0.93, P=0.035) were significant prognostic factor for PDAC. Conclusions: Pancreatectomy impaired insulin secretion and improve insulin resistance especially in PDAC patients. About half of PDAC patients demonstrated the improvement of glucose tolerance after surgery. Of note, glucose tolerance differed between PDAC and other disease, and affect the survival outcome for PDAC patients.
Primary liver angiosarcoma and factors associated with improved outcomes: An analysis of the National Cancer Database.
Authors: Prantesh Jain, Gino Cioffi, Nirav Patil, Aman Opneja, Asrar Alahmadi, David Lawrence Bajor, Joel N. Saltzman, Patrick J. Getty, John Brian Ammori, Aashish D. Bhatt, David B. Mansur, Richard T. Lee, Ankit Mangla
Journal: Journal of Clinical Oncology (2020)

498 Background: Primary liver angiosarcoma (LAS) is a rare and aggressive tumor of the liver. In this analysis of the national cancer database (NCDB) we sought the risk of mortality and factors associated with survival amongst patient diagnosed with LAS. Methods: Patients diagnosed with hepatocellular carcinoma (HCC) or LAS from 2004 – 2014 were identified in the NCDB. The Kaplan-Meier method with the log-rank test was used to calculate survival for HCC and LAS patients. Additional analyses were performed on the cohort with LAS to assess the impact of surgery, chemotherapy, radiation therapy (RT) and facility type on overall survival (OS). Multivariable analyses using cox proportional methods, adjusted for age, sex, Charlson/Deyo score, race, ethnicity, insurance status, facility location and type, surgery status, and chemotherapy status were performed to obtain adjusted hazard ratio (aHR). Results: Total of 118,066 patients with HCC and 346 patients with LAS were identified in the database. Median survival for HCC patients was 11.9 months (95% CI: 11.7-12.2) and 2.0 months for LAS patients (95% CI: 1.8 – 2.4). Risk of mortality was higher for patients with LAS compared to those with HCC (aHR (95% CI): 2.23 (1.97 - 2.53), p &lt; .0001). Among the LAS patients, those who received surgery had a median survival of 8.6 months (95% CI: 5.6 - 17.3), and 1.8 months for those who did not (95% CI: 1.48 - 1.94). Risk of mortality was lower in patients who received surgery compared to those who did not (aHR (95% CI): 0.23 (0.15 - 0.37), p &lt; .0001). Patients treated at and academic center had a higher median survival (3.3 months, 95% CI: 2.2 - 4.1) then those treated at a non-academic center (1.5 months, 95% CI: 1.2 - 1.8). Though, there was no significant difference in OS (aHR (95% CI): 0.48 (0.21 - 1.10), p = 0.082). A very small number of patients received chemotherapy or RT to conduct a meaningful analysis. Conclusions: Patients diagnosed with primary LAS have a worse OS compared to those with HCC. Amongst patients with primary LAS, surgical resection is associated with best survival outcomes. Treatment at an academic center is associated with better median survival, although OS did not reach statistical significance in our analysis.
Real-world rates of hematology lab abnormalities and associated cost among metastatic pancreatic cancer (mPC) therapeutic regimens.
Authors: Gabriela Dieguez, Andy Surinach, Daniel Mercer, Paul Cockrum, George P. Kim, Pamela Pelizzari
Journal: Journal of Clinical Oncology (2020)

670 Background: Low hematologic counts are a common, costly side effect of chemotherapy. This observational study examines rates and associated cost to treat. Methods: Data on adverse events (AEs) were extracted from the clinical Flatiron Health database for mPC patients (pts) from 01/2014-01/2019. Anemia, neutropenia, and lymphopenia occurrence was assessed via diagnosis codes and structured lab data. Costs due to AEs were derived from a claims analysis of mPC pts from 2013-2017 in Medicare Limited Data Set claims. Mean adjusted incremental costs (ICs) were estimated by comparing 30-day costs of pts with and without AEs, with controls selected among pts without AEs with the same regimen and line of therapy, when at least 80 cases/controls were identified. Results: 4592 treated mPC pts were identified (median age at diagnosis: 68y, IQR: 61 – 75). 1138 pts were treated with FOLFIRINOX (FFX) in first-line (1L), 2295 pts with 1L gemcitabine plus nab-paclitaxel (gem-nab), 218 pts with second-line (2L) FOLFOX, 56 pts with 2L FOLFIRI, and 178 pts with 2L liposomal irinotecan (nal-IRI) based therapy. Observed rates of anemia and neutropenia are shown in the table below. Lymphopenia rates were similar across regimens and ICs were not statistically significant. ICs for patients with any grade anemia were $3864, $3818, $3536, $3978, and $2963 for FFX, gem-nab, FOLFOX, FOLFIRI, and nal-IRI treated pts, respectively. ICs for pts with any grade neutropenia were $2382 for FFX, $2440 for gem-nab, $2688 for FOLFOX, $3551 for FOLFIRI and $2307 for nal-IRI. Conclusions: Any grade anemia ICs ranged from $2963 [$1544, $4400] (nal-IRI) to $3978 [$2241, $5817] (FOLFIRI), and any grade neutropenia ICs ranged from $2307 [$703, $4313] (nal-IRI) to $3551 [$1227, $6039] (FOLFIRI). Pts treated with nal-IRI had similar any grade AE rates but lower ICs, which suggest lower severity of AEs. These results are consistent with Flatiron Health’s lower rates of grades 3+ neutropenia and anemia. [Table: see text]
Real-world evidence data (RWED) of financial toxicity (FT) in patients (pts) receiving cancer immunotherapy treatments.
Authors: Daniel A. Vorobiof, Lior Hasid, Alon Litvin, Irad Deutsch, Eliran Malki
Journal: Journal of Clinical Oncology (2020)

90 Background: RWED denotes data accumulated via EHR as well as cutting edge technology paired with consumer mobile devices. We are reporting data on 105 pts, users of Belong.life, a worldwide mobile application, who received immunotherapy for their various cancers and were asked to reply to a short, targeted survey on their FT while on treatment. Methods: 105 pts anonymously and voluntarily replied to a survey which included 14 general information questions and those describing FT, its most common encountered causes and their personal financial coping strategies. Results: 79% of the pts were USA based. 21% of the pts were &lt; 50 years of age (yoa), 32% were 51-60 yoa and 47% were &gt; 61 yoa. Pts’s stages were Stage 3 in 23% and 4 in 62% with unknown in 15%. There were 36% males and 64% females. The most common cancer diagnosis was lung in 46% followed by kidney in 17%, malignant melanoma in 14% and colorectal in 10%. The prevalent immunotherapy drugs were nivolumab and pembrolizumab in 36% respectively, and ipilimumab in 14% and durvalumab in 10%. Frequently reported FTs were high medical copayments in 35% of the pts, loss of income in 33% and high drugs and treatments copayments in 21%. 41% of the pts were insured by Medicare and 25% by Medicaid and other HMOs. Only 48% of the pts were aware of possible financial difficulties as a result of their diagnosis and treatment, and 34% received pre-treatment financial advice from their doctors which reduced the reported FT from 48% to 30%. When asked about coping strategies, 39% used personal savings, 28% trimmed their private expenses, and 24% received financial support from their families and friends. Conclusions: 105 users of the Belong.life application reported on their FTs experienced while receiving cancer immunotherapy. FT was most prevalent in the older group ( &gt; 61 yoa) due to high medical and treatment copayments. Nearly half of the pts was not aware of the possible FT and only 38% received advisory information from their doctors. Reduced FT prevalence (from 48% to 30%) was reported by those informed pts. Physicians should become aware of their pts’s possible risks for FTs, therefore appropriate advice should be given prior to immunotherapy initiation.
Establishing novel mutation subtypes in peritoneal carcinomatosis of appendiceal origin.
Authors: Mary Garland-Kledzik, Anthony Joseph Scholer, Adam Khader, Juan Santamaria-Barria, Javier Orozco, Alessio Pigazzi, Diego M. Marzese
Journal: Journal of Clinical Oncology (2020)

200 Background: Appendiceal cancer (AC) is a rare disease process with complex treatment strategies. The objective of this study was to identify mutation-based genetic subtypes that may differ from the current histological classification, compare genetic make-up of primaries and metastases, and to find novel targetable alterations. Methods: The analysis involved the curation and normalization of mutation panels from adenocarcinoma and mucinous adenocarcinoma (n = 196) stored in the AACR GENIE Database v6.0. Genes mutated in less than two patients and tumors profiled with incomplete mutation panels were excluded from the study. The optimal number of AC subtypes was established using the Non-negative Matrix Factorization algorithm. Statistical comparisons of mutation frequencies were performed by using the Pearson’s χ 2 test. Results: AC patients were stratified into five mutation subtypes. AC0 had no mutations in the 41 genes in the study. The most frequently mutated genes varied between the subtypes. AC1: KRAS (91.9%) and GNAS (77.4%); AC2: KRAS (52.5%), APC (32.5%), and GNAS (30%); AC3: KMT2D (38.7%), TP53 (38.7%), KRAS (35.5%), EP300 (22.6%); and AC4: TP53 (97.2%), KRAS (77.8%), and SMAD4 (36.1%). Additionally, AC3 was less likely to be mucinous (22.6% v 50.0-74.2%, p &lt; 0.001) and had a higher mutation frequency (3.6 v 0-3.1, p &lt; 0.001). There were no differences between primaries and metastases (p = 0.35). Conclusions: Characterization of these subtypes suggest a need for molecular rather than anatomic staging for AC. Histone regulation by KMT2D and EP300 may be considered for targeted therapy for patients with AC3. A prospective comparison of subtype prognosis and response to surgery and adjuvant treatment is needed.
Openact: Phase 2, Open-Label Study of Sipuleucel-T in Metastatic Castrate-Resistant Prostate Cancer (MCRPC)
Authors: J. Corman, N. Dawson, S. Hall, C. Nabhan, A. Ferrari, A.J. Armstrong, M.I. Murdock, F. Stewart, N. Sheikh, D.P. Petrylak
Journal: Annals of Oncology (2012)
Clinicopathological features of pancreatic cancer-related diabetes.
Authors: Michael Lee, Hui-Li Wong, Erica S. Tsang, Sean McKay Fenlon Addison, James T. Topham, Joanna Karasinska, Steve Kalloger, Jonathan M. Loree, David F. Schaeffer, Daniel John Renouf
Journal: Journal of Clinical Oncology (2020)

675 Background: Epidemiological studies suggest pancreatic ductal adenocarcinoma (PDAC) may be strongly interrelated with diabetes. However, little is known about the clinicopathological features of pancreatic cancer related diabetes. Methods: A retrospective chart review was undertaken of all patients with advanced PDAC treated with at least one cycle of palliative chemotherapy at BC Cancer, Vancouver between Jan 2012- Dec 2015. Diagnosis of diabetes was determined by consultation documentation and/or fasting glucose &gt; 7mmol/L or HbA1c &gt; 48mmol/L. Peripancreatic diabetes is defined as diabetes diagnosis &lt; 3 years prior to PDAC diagnosis. Results: 578 patients were identified with median age 66 (49-81), 54.6% male, 39.5% non-smoker and 63.5% ECOG 0/1. 27.3% confirmed diabetics, of which 75.8% (119/157) have peripancreatic diabetes. At initial diagnosis, 11.2% were deemed upfront resectable, 44.0% borderline/locally advanced, and 55.1% metastatic. Median overall survival (OS) for the cohort based on stage of disease at initial diagnosis for borderline, locally advanced and metastatic was 22 months (16.1-27.9), 12 months (10.1-13.9) and 6 months (5.0-7.0) respectively. There was no association with diabetes status and OS noted (p = 0.58). Statistical differences were noted in BMI (24.1 v 26.1, p = 0.003), and proportion of Charlson comorbidity index (CCI) of 2 (2.2 v 88.3%, p &lt; 0.01) between non-diabetic and diabetic patients respectively. Statistical difference between peripancreatic diabetes compared to long-term diabetes were noted in resectable status (18.6 v 7.6%, p = 0.048), weight loss &gt; 2kg (78.6 v 60.5%, p = 0.035), hypertension (25.9 v 59.8%, p = 0.002) and dyslipidemia (18.5 v 42.7%, p = 0.024). Conclusions: The majority of patients diagnosed with advanced PDAC with diabetes appeared to develop diabetes within 3 years prior to diagnosis. Further studies to assess the potential role of pancreatic cancer screening investigations in newly diagnosed diabetics are warranted.
Nationwide survey of pancreaticobiliary maljunction focusing on biliary cancer incidence in Japan.
Authors: Mitsuo Shimada, Hiroki Ishibashi, Yuji Morine, Masayuki Kubota, Hideki Fujii
Journal: Journal of Clinical Oncology (2020)

587 Background: Pancreaticobiliary maljunction (PBM) is known to be a unique entity closely related to biliary carcinogenesis. We herein report update analysis of PBM focusing on biliary cancer as third report of Japan-nationwide survey. Methods: From 1990 to 2015, 3,419 patients with PBM were registered at 141 medical institutions in Japan. 3,289 (1,344 pediatric and 1,945 adult patients) out of 3,419 patients were fully investigated, according to presence of bile duct dilatation (BDD), age (pediatric or adult), etc. Results: In pediatric patients, only 3 cases with BDD (0.124%) had bile duct cancers. On the other hand, in adults, biliary cancer incidence was 21.1% in patients with BDD and 43.5% in patients without BDD. The rates were extremely high in comparison with 0.0174% of Japanese prevalence of biliary cancer 2013. The cancer incidences of bile duct, gallbladder and both in adults with BDD/without BDD were 6.7%/4.1%, 13.0%/37.3%, and 1.4%/2.1%, respectively. In patients without associated biliary cancers, extrahepatic bile duct resection (EHBDRx) combined with cholecystectomy was performed in 89.5% of adults with BDD, while, in only 31.2% adults without BDD. Regarding the new biliary cancer occurrence of patients having follow-up data, the rate was 0.3% in 354 patients with BDD who underwent EHBDRx, while that was 4.0% in 75 patients without BDD who underwent simple cholecystectomy. In patients without BDD, cancer incidence (6.7%) in the late period (2010 to 2015) was higher than those (3.3% and 3.5%) in early and middle period (1990 to 1999, and 2000 to 2009). Conclusions: This updated nationwide survey of PBM revealed characteristics of associated and newly occurred biliary cancers, and could be widely used as a reference data for diagnosis and treatment of PBM.
A phase III study of futibatinib (TAS-120) versus gemcitabine-cisplatin (gem-cis) chemotherapy as first-line (1L) treatment for patients (pts) with advanced (adv) cholangiocarcinoma (CCA) harboring fibroblast growth factor receptor 2 (<i>FGFR2</i>) gene rearrangements (FOENIX-CCA3).
Authors: Mitesh J. Borad, John A. Bridgewater, Chigusa Morizane, Rachna T. Shroff, Do-Youn Oh, Markus H. Moehler, Junji Furuse, Karim A. Benhadji, Helen He, Juan W. Valle
Journal: Journal of Clinical Oncology (2020)

TPS600 Background: Pts with adv CCA have poor survival outcomes, and chemotherapy offers limited survival benefit (5-year survival rates, 5–10%; median overall survival [OS], 8–12 months). FGFR2 gene rearrangements are known to be early drivers of oncogenesis in ~15% of pts with intrahepatic (i) CCA. Futibatinib, an oral, highly selective, irreversible FGFR1-4 inhibitor has shown antitumor activity against a broad spectrum of FGFR-deregulated tumors in preclinical studies. In a previous study, futibatinib demonstrated clinical activity and tolerability in heavily pretreated pts with adv CCA harboring FGFR2 gene rearrangements. This phase 3 trial (FOENIX-CCA3) is designed to evaluate futibatinib vs gem-cis as 1L therapy for pts with adv iCCA harboring FGFR2 rearrangements. Methods: FOENIX-CCA3 is a multicenter, open-label, randomized phase 3 study that will be conducted in pts with metastatic or unresectable iCCA harboring FGFR2 rearrangements (assessed at screening by a central laboratory). Pts must have an ECOG performance status of 0 or 1 and should not have received previous systemic anticancer therapy for adv disease (adjuvant/neoadjuvant therapy ≥6 mo prior to randomization is permissible). Pts with clinically-significant alterations in calcium-phosphorus homeostasis or ectopic mineralization/calcification will be excluded. Approximately 216 pts will be randomized (1:1 ratio) to receive 20 mg futibatinib once daily until disease progression or other discontinuation criteria are met or gem-cis (on days 1 and 8 of a 21-day cycle) for 8 cycles or until disease progression, whichever occurs first. Pts will be stratified by prior surgical excision (yes vs no), geographic region, and locally adv vs metastatic disease. The primary endpoint is progression-free survival (PFS) assessed by independent central review (ICR). Secondary endpoints include objective response rate and disease control rate based on ICR, OS, PFS per investigator assessment, and safety. The anticipated start date is in April, 2020.
Error in the dosage of Methotrexate in the EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis
Authors: Dennis Scheicht
Journal: Annals of the Rheumatic Diseases (2020)

Error in the dosage of Methotrexate in the EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitisThe EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis (AAV) 1 are a pillar in the treatment of patients with these diseases worldwide.Hence, it is of the utmost importance that information, especially dosing be correct and therefore reliable.More than in some other rheumatic diseases AAV oftentimes requires treatment from a multidisciplinary team.For physicians from other specialties dosing might not be as familiar as it is for rheumatologists.Statement 7 of the recommendations suggests a dose of Methotrexate with 20-25 mg/kg/week for remission maintenance of AAV.This recommended dose would almost certainly be toxic and lead to complications or even death.Patients die every year from wrong dosing of Methotrexate.I suggest that in the future, before publishing recommendations for the management of rheumatic diseases an additional layer of security be implemented by separate review of every suggested dose of every medication in the publication for mistakes or typos because every mistake, howsoever small, can have far reaching consequences for our patients.