bluuebunny/crossref_metadata_2025 huggingface dataset:
Multicenter retrospective observational study of pancreatic cancer with positive peritoneal lavage cytology intended for surgical resection.
Authors: Todaka Akiko , Nara Satoshi , Motoi Fuyuhiko , Morinaga Soichiro , Hama Naoki , Higuchi Ryota , Konishi Masaru , Shirakawa Hirofumi , Tsumura Hidetaka , Okuyama Hiroyuki , Matsui Hiroto , Shioji Kazuhiko , Sugimachi Keishi , Asagi Akinori , Mizuno Nobumasa , Fukutomi Akira , Furuse Junji
Published: February 2020

695

Background: Although macroscopically curative resection has been performed for pancreatic cancer with positive peritoneal lavage cytology (CY1), the prognosis is poor in most reports. In 2013, the JASPAC01 trial showed that S-1 was superior to Gemcitabine (GEM) as adjuvant chemotherapy for resected pancreatic cancer, and S-1 was also administered to the patients with CY1 who had undergone macroscopically curative resection. Methods: This is a multicenter retrospective observational study that collected data of the patients with pancreatic adenocarcinoma who were diagnosed with CY1 between 2007 and 2015 and had no other noncurable factors. Results: One hundred twenty-seven patients were enrolled from 14 institutions, and 3 were excluded due to liver metastasis or non-adenocarcinoma. The median age was 67 years old and almost patients had PS 0 or 1. Of the 124 patients, 114 underwent macroscopically curative resection and the median overall survival (OS) and recurrence free survival (RFS) were 16.7 and 7.2 months. Of the resected patients, 80 (70%) had no early recurrence and started postoperative adjuvant chemotherapy. Adjuvant chemotherapy regimens were S-1 in 43 patients (54%), GEM in 31 (39%) and others in 6 (7%). The median OS was 21.0 months with S-1 and 19.2 months with GEM (HR: 0.73, 95%CI: 0.44-1.22, P = 0.23), whereas the median RFS was 10.2 and 7.1 months (HR: 0.58, 95%CI: 0.36-0.95, P = 0.03), respectively. Conclusions: After the report of JASPAC01, most patients with pancreatic cancer with CY1 received macroscopically curative resection and treated with S-1 as adjuvant therapy, however the efficacy was insufficient. We should consider appropriate treatment strategies for patients with pancreatic cancer with CY1 intended for surgical resection.
Multicenter phase I/II study of intravenous gemcitabine + nab-paclitaxel combined with intraperitoneal paclitaxel for pancreatic ductal adenocarcinoma patients with peritoneal metastasis.
Authors: Yamada Suguru , Fujii Tsutomu , Yamamoto Tomohisa , Takami Hideki , Yoshioka Isaku , Yamaki So , Sonohara Fuminori , Shibuya Kazuto , Motoi Fuyuhiko , Hirano Satoshi , Murakami Yoshiaki , Inoue Hitoshi , Hayashi Masamichi , Kodera Yasuhiro , Sekimoto Mitsugu , Satoi Sohei
Published: February 2020

702

Background: Pancreatic ductal adenocarcinoma (PDAC) patients with peritoneal metastasis (peritoneal deposits and/or positive peritoneal cytology) have an extremely poor prognosis, and an effective treatment strategy remains elusive. Methods: The aim of this study were to determine the recommended dose (RD) for a combination of intravenous (IV) gemcitabine, intravenous nab-paclitaxel, and intraperitoneal (IP) paclitaxel in chemotherapy-naive PDAC patients with peritoneal metastasis and to evaluate the clinical efficacy and safety. Gemcitabine and nab-paclitaxel was administered IV combined with paclitaxel IP on days 1, 8 and 15, followed by 1 week of rest. The frequency of dose-limiting toxicity was evaluated and the RD was determined. The primary endpoint of the phase II part was 1-year overall survival (OS) rate. The secondary endpoints were antitumor effect, symptom relief effect, safety and OS. Results: In the phase I part, RD for IV gemcitabine, IV nab-paclitaxel and IP paclitaxel were determined as 800 mg/m2, 75 mg/m2, and 20 mg/m2, respectively. A total of 46 patients were enrolled in the phase II part and drugs were delivered at the RD. All patients had positive intraperitoneal cytology and 29 patients (63.0%) had the peritoneal dissemination. The median treatment period was 6.0 (0-22.6) months. The response rate and disease control rate were 45.7% and 95.7%, respectively. Ascites disappeared in 40.0% and cytology turned negative in 67.4%. Median CA19-9 decrease ratio was 84.4 (16.9-99.1) %. The median survival time was 12.8 (3.1-32.7) months, and the 1-year survival rate was 52.2%. Finally, conversion surgery was performed in 8 (17.4%) patients and those who received conversion surgery survived significantly longer than those who did not (not reached vs. 11.7 months, P = 0.0070). Grade 3/4 hematologic toxicities occurred in 76.0% and nonhematologic adverse events in 15.0%, of which 6.5% were bowel obstructions. Conclusions: This regimen has shown promising clinical efficacy with acceptable tolerability in chemotherapy-naive PDAC patients with peritoneal metastasis. Clinical trial information: 000018878.
Randomized phase II trial of chemoradiotherapy with S-1 versus combination chemotherapy with gemcitabine and S-1 as neoadjuvant treatment for resectable pancreatic cancer (JASPAC 04).
Authors: Toyama Hirochika , Sugiura Teiichi , Fukutomi Akira , Asakura Hirofumi , Takeda Yuriko , Yamamoto Kouji , Hirano Satoshi , Satoi Sohei , Matsumoto Ippei , Takahashi Shinichiro , Morinaga Soichiro , Yoshida Makoto , Sakuma Yasunaru , Iwamoto Hidetaka , Shimizu Yasuhiro , Uesaka Katsuhiko
Published: February 2020

724

Background: Although neoadjuvant treatment (NAT) has been widely employed for resectable pancreatic ductal adenocarcinoma (PDAC), it is still unclear what kind of regimen is recommended. The aim of the study is to investigate which chemoradiotherapy (CRT) with S-1 or combination chemotherapy with gemcitabine (GEM) and S-1 is more promising as NAT for resectable PDAC in terms of effectiveness and safety. Methods: Patients with resectable PDAC were enrolled and randomly assigned into either CRT group or chemotherapy group. In the CRT group, a total radiation dose of 50.4 Gy in 28 fractions was administered and S-1, at a dose of 30, 40 or 50 mg according to the body surface area, was orally provided twice a day on the same day of irradiation. In the chemotherapy group, GEM was intravenously administered at a dose of 1000 mg/m2 on day 1 and 8 and S-1 was orally provided at a dose of 30, 40 or 50 mg according to the body surface area twice daily on day 1 to 14 followed by one week reset. Patients in the chemotherapy group received two cycles of this regimen. Surgery was performed between 15 and 56 days after the last day of NAT. The primary endpoint was 2-year progression-free survival (PFS) rate. With 50 patients in each group, the study had 80% power assuming a threshold 2-year PFS rate of 25% and an expected 2-year PFS rate of 40% at 0.05 one-sided alpha. The trial was registered with the UMIN Clinical Trial Registry as UMIN000014894. Results: From April 2014 and April 2017, 103 patients were enrolled from 11 institutions in Japan. One was excluded because of ineligibility, therefore 51 patients in CRT group and 51 patients in chemotherapy group constituted the intention-to-treat analysis. The 2-year PFS rate was 45% (90% CI, 33-60%) in the CRT group and 55% (43-65%) in the chemotherapy group (p = 0.52). The hazard ratio for chemotherapy to CRT was 0.78 (0.46-1.31). The median survival time was 37.7 (95% CI, 30.3-NE) in the CRT group and NE (29.9-NE) in the chemotherapy group (p = 0.30). There was no treatment-related death in both groups. Conclusions: Combination chemotherapy with GEM and S-1 may be more promising compared with CRT with S-1 as NAT for resectable PDAC. Clinical trial information: UMIN000014894.
Outcomes and efficacy of neoadjuvant chemoradiation versus chemotherapy in localized pancreatic cancer.
Authors: Chopra Asmita , Hodges Jacob C. , Olson Adam , Burton Steven A. , Lee Kenneth K. , Bahary Nathan , Singhi Aatur D. , Boone Brian A. , Lotze Michael T. , Hogg Melissa E. , Zeh Herbert , Zureikat Amer H.
Published: February 2020

727

Background: Neoadjuvant therapy is increasingly used for pancreatic cancer (PDA). The comparative efficacy of neoadjuvant chemotherapy (NC) versus chemoradiation (NCRT) remains uncertain. We aimed to compare NC and NCRT on survival outcomes and pathologic endpoints of PDA. Methods: Single-center analysis of PDAs treated with NC or NCRT between 2008-2018. Average treatment effects (ATE) were estimated after matching cases to controls using Mahalanobis distance nearest-neighbor matching. Competing risk survival analysis and inverse probability weighted estimates (IPWE) were used for disease free survival (DFS) and overall survival (OS) respectively. Results: Of 418 patients (median age 67yrs, 51% females), 327 received NC and 91 received NCRT. NCRT patients had more locally advanced disease, cross-over NC regimens (gemcitabine & 5-FU based), longer neoadjuvant therapy duration, open surgery and vascular resection (all p < 0.05). NCRT was associated with lower LN positivity, LNR, LVI and PNI, higher R0 rates, and higher near complete and complete pathologic responses (all p < 0.05, table). After adjustment, NCRT was associated with a significant reduction in LN positivity [95%CI = (-)0.41-(-)0.07; p = 0.007] and LVI [95%CI = (-)0.36-(-)0.03; p = 0.02]. While NCRT was associated with improved OS on UVA (25.5 vs. 21.6 months; p = 0.04), it was not significantly associated with OS by IPWE after adjusting for adjuvant therapy [95%CI = (-)5.02-16.3; p = 0.3] or DFS on competing risk analysis (95%CI = 0.78-1.31; p = 0.96). Conclusions: Although NCRT is associated with improved pathologic surrogates, it is not associated with improved survival in PDA. [Table: see text]
Clinical significance of monitoring KRAS in tissue and plasma of pancreatic cancer patients.
Authors: Watanabe Fumiaki , Suzuki Koichi , Rikiyama Toshiki
Published: February 2020

745

Background: KRAS monitoringprovides valuable information for early diagnosis and prediction of treatment outcome in colorectal cancer. KRASmutation is observed in only half of colon cancer patients, whereas it is detected in 90% of pancreatic cancer patients. Therefore, investigating tumor DNA in plasma by KRAS monitoringmay be even more valuablein pancreatic cancerpatients. In this study, we elucidated the clinicalsignificance of KRASmonitoring in pancreatic cancer patients during treatment. Methods: KRASin tumor tissues was analyzed for mutations by Scorpion ARMS or RASKET in 83 patients with pancreatic tumors. KRASin plasma was analyzed for mutations(G12D, G12V, G12C, G12A, G12S, G12R, G13D, Q61L, and Q61H) using droplet digital polymerase chain reaction in 88 patients who underwent the curative surgery (N = 45) or the chemotherapy (N = 33) and who had KRAS mutation in their tissues. Results: KRASmutation in tumor tissues was detected in 74 of 83 patients (89.2%). These 74 patients showed significantly poorer prognosis (MST; 32) than the seven patients without mutation (p = 0.03), whose MST were 193. Monitoring of KRASin plasma revealed KRASmutation in 35 of 88 patients (39.8%). In patients who underwent the chemotherapy (N = 33), 2years OS of patients who detected KRASmutation in plasma (N = 23) was 16.4% and them which not detected it (N = 10) was 53.3% (p = 0.18). But in the curative resection group (N = 45), 3years OS of patients who detected KRASmutation in plasma (N = 12) was 16.7% and them which not detected it (N = 33) was 68.2% (p = 0.00). Conclusions: KRASmutation in tissue and plasma could be a valuable predictive and prognostic biomarker in pancreatic cancer patients.
Analysis of pancreatobiliary adenocarcinoma (PBC) treatment response and resistance utilizing circulating tumor DNA (ctDNA).
Authors: Banerjee Madhulika , Boiles Alejandro Recio , Veeravelli Sumana , Leiva Jorge Andres , Saboda Kathylynn , Roe Denise , McBride Ali , Babiker Hani M.
Published: February 2020

758

Background: Accurate disease monitoring in PBC is instrumental for optimal therapeutic decision-making. CA 19-9 is the most utilized biomarker, though it has limited sensitivity/specificity and cannot be used in CA 19-9 non-secretors (n-S). ctDNA is a potentially helpful monitoring aid and surrogate for PBC n-S. Serial ctDNA could identify emerging resistant driver mutations. Our study prospectively examined ctDNA in PBC patients receiving treatment and retrospectively correlated it with clinical response. Methods: We performed genomic testing of ctDNA from metastatic PBC patients’ plasma from 11/2016 to 08/2019. This included 77 patients, of those, 18 had >1 ctDNA measurement with 49 correlative data points in total. Demographics, serial CA 19-9 levels and imaging results were collected. ctDNA analysis by parallel sequencing of amplified target genes (74) using Guardant360 was obtained. We correlated imaging and CA 19-9 responses with molecular alterations in patients receiving systemic chemotherapy. Descriptive statistics and logistic regression of the data was performed. Results: Of those included, median age was 66 yo, 50% male, and 92% pancreatic ductal adenocarcinoma. Baseline ctDNA showed 103 mutations including TP53 12.6%, KRAS 9.7%, MET 6.8%, APC, ARID1A and NF1 4.8% each, and others < 3%. 44% of patients were n-S with 75% having both TP53 and KRAS mutations. APC, ARID1A, and NF1 were only present in n-S. 91% vs 90% KRAS and 84% vs 78% TP53 of n-S and secretors (S), respectively, had correlation between ctDNA levels and imaging response. S TP53 and KRAS mutations correlated to CA19-9 levels and scans in 78% and 70% responses. New TP53 subclonal variant mutations were the most common resistance mutations for all progressions (75%). A logistic regression model of imaging progression on change in CA19-9 secretion and TP53 or KRAS expression was not statistically significant. Conclusions: Baseline ctDNA level changes ( TP53 and KRAS) can potentially act as a biomarker of response in PBC, specifically in n-S. TP53 subclonal mutations were the most common resistant alterations at progression and can be explored as future targets. This is being explored in larger prospective trials.
The effect of TGF-β on PD-L1 expression on PDAC TAMs.
Authors: Trebska-McGowan Katarzyna , Makowski Liza , Alvarez Marcus A. , Kansal Rita , Husain S. Mazher , Pingili Ajeeth K. , Glazer Evan Scott
Published: February 2020

764

Background: Pancreatic Ductal Adenocarcinoma (PDAC) has less than a 10% five year survival and will become the second leading cause of US cancer mortality in the next decade. Immunotherapy, such as checkpoint inhibition against anti-Programmed death-ligand 1 (PD-L1) has not been successful in the treatment of PDAC patients. Both tumor associated macrophages (TAMs) and the TGF-β protein are ubiquitous in PDAC tumors. We hypothesize that TGF-β increases the overall number of TAMs and degree of PD-L1 expression of TAMs in PDAC. Methods: Our lab has a mouse pancreatic cancer cell line derived from a genetically engineered mouse model (KPC mice that spontaneously form PDAC tumors that are similar to human PDAC). We orthotopically implanted this cell line into the pancreas of immunocompetent C57BL/6 (B6) mice. In groups of 5 each, mice were treated with saline (control) or TGF-β. We investigated tumor burden, the number of TAMs (CD45+, CD11b+F4/80hi, Ly6C−, Ly6G−/lo) in the tumors with flow cytometry and the percentage of TAMs expressing PD-L1 in the pancreas and metastatic lesions in the liver. Results: As a percent of leukocytes in the tumor, PDAC liver metastases had more TAMs compared to tumors in the pancreas (33 ± 5% vs 10 ± 4%, P = 0.001). Compared to controls, TGF-β treatment significantly increased the percent of PD-L1 expressing TAMs (32 ± 6 % vs 12 ± 5%, P = 0.013, see Figure) in the pancreas but no effect was evident on TAM density. In liver metastases, treatment with TGF-β decreased the overall TAM density (P = 0.039) but did not affect the number of PD-L1 positive TAMs. Conclusions: TGF-β plays pivotal role in the progression of PDAC and demonstrates context dependent activity. Our results suggest that an immunosuppressive effect mediated by PD-L1 expression on TAMs may be initiated by TGF-β. Future investigations will focus on understanding the role of the PDAC – TAM interaction to develop effective immune therapies for PDAC patients.
Genomic associations in metastatic pancreatic cancer (mPC).
Authors: Rengan Anil Kumar , Dotan Efrat , Devarajan Karthik , Vijayvergia Namrata
Published: February 2020

765

Background: mPC is an aggressive cancer, and molecular profiling provides further insight into pathogenesis and treatment. We sought to illustrate the molecular landscape of mPC in relation to post-metastatic survival and VTE incidence. Methods: With IRB approval, we retrospectively analyzed charts of mPC patients who underwent molecular profiling. Fisher’s exact test (categorical) and Mann-Whitney test (continuous) were used to compare groups. Log-rank test, Cox proportional hazards model and weighted Cox regression were used for survival analysis. Results: Between 2009 and 2018, 98 out of 502 mPC patients (19.5%) underwent molecular testing. Of these, 70% were tested after 2015. The most common mutations were in KRAS (79.2%), TP53 (59.0%), CDKN2A (35.9%), BRCA (16.4%), PIK3CA (9.4%) and SMAD4 (7.4%). Concurrent KRAS and TP53 mutations were found in 62.3% of patients. KRAS mutation was positively associated with Jewish ancestry (OR 2.3; p < 0.05), and TP53 mutation was positively associated with younger age at diagnosis (63.5 vs. 67 years; p < 0.05). KRAS and TP53 mutations were negatively associated with tobacco use (OR 0.43 and 0.3, respectively; p < 0.05). There was no association between any mutation and metastatic site. Both KRAS and TP53 mutations were positively associated with VTE (OR 2.55 and 2.71, respectively; p < 0.05). Interestingly, TP53 mutation portends worse survival (HR 3.85; p < 0.05) whereas CDKN2A mutation confers improved survival (HR 0.55; p < 0.05). No patient received targeted therapy for their specific mutations. Conclusions: Molecular testing is becoming more prevalent in the mPC treatment paradigm. Among our cohort, concurrent KRAS and TP53 mutations were frequently identified. Incidence rates of the most common mutations were similar to those observed in prior literature. KRAS and TP53 mutations were associated with higher incidence of VTE. TP53 mutation was associated with poorer prognosis.
Quality of timely adjuvant chemotherapy for veterans with colorectal cancer.
Authors: Martin Richard Lewis , Edwards Gretchen C. , Samuels Lauren R. , Roumie Christianne L.
Published: February 2020

78

Background: National Comprehensive Cancer Network (NCCN) recommends adjuvant chemotherapy for patients with high risk stage II or stage III colorectal cancer (CRC). Treatment within 8 weeks of surgery improves disease free survival and decreases recurrence. National Veterans Health Administration (VHA) CRC data demonstrated adherence to this standard; however, there was regional variation. We sought to describe time to treatment at a Southeast Regional VHA facility to determine local targets for quality improvement initiatives. Methods: We retrospectively reviewed 705 electronic medical records of patients who underwent colorectal surgery from January 1, 2000 to December 31, 2015 at VHA Tennessee Valley Healthcare System. Two trained clinician abstractors reviewed standard elements (k = 0.79 – 0.92). The population included patients with pathological stage high risk II or III CRC and excluded those with metastatic disease or documented NCCN defined exclusion from chemotherapy. We analyzed 2 populations; chemotherapy received and a sensitivity analysis population of patients who were eligible for, but did not receive, chemotherapy (no documentation of NCCN ineligibility or declined). The primary outcome was chemotherapy within 8 weeks of surgery, evaluated during three time periods due to changes in NCCN guidelines. Results: Of 705 colorectal surgeries, we excluded 262 for non-cancers, 220 for stage I or low-risk stage II cancers, and 46 for NCCN defined exclusion, yielding 177 cases: 120 colon and 57 rectal cancers. Patients were 98% male, 85% white, and median age 64 years [Interquartile Range 60, 70]. Among those receiving chemotherapy (123/177 [69.5%]), median time to treatment was 50.5 days [40,64]; with 63% receiving chemotherapy within 8 weeks. Results varied over time. Between 2000-2004 75% received within 8 weeks; 2005-2009, 62%; 2010-2015, 41%. Including all eligible patients, the proportion receiving timely treatment declined; overall 44%; 2000-2004, 57%; 2005-2009, 45%; 2010-2015, 25%. Conclusions: Improving care processes for patients with CRC can improve timely treatment. Exploring barriers such as prolonged hospitalization, wound healing, and port placement may reveal areas for quality improvement.
Impact of high-risk features for stage II adenocarcinoma of the appendix.
Authors: Akce Mehmet , Zakka Katerina Mary , Penely Mckenna , Jiang Renjian , Alese Olatunji B. , Shaib Walid Labib , Wu Christina , Behera Madhusmita , El-Rayes Bassel F.
Published: February 2020

795

Background: Clinico-pathological high risk features are frequently utilized in adjuvant chemotherapy (AC) decisions in stage II colorectal cancer and their utility in stage II appendiceal adenocarcinoma (AA) is less established. The aim of this study is to determine the impact of high risk features on clinical outcomes and whether high risk features are predictive of AC benefit in stage II AA. Methods: Patients with pathological stage II AA between 2010 and 2015 were identified from the National Cancer Database (NCDB) using ICD-O-3 morphology and topography codes: 8140, 8480 and C18.1. High risk stage II AA was defined as having at least one of the following clinicopathological features: T4 tumor, < 12 lymph nodes examined, poorly differentiated histology, positive margins, or lymphovascular invasion. Patients with none of these features were defined as low-risk. Results: A total of 1,040 patients were identified. 51.0% males, 84.5% Caucasian; median age 61 (range, 19-90). 46.4% were determined to have high-risk stage II AA. High-risk status was associated with worse OS compared to low-risk in univariate (HR 1.55; 95% CI 1.18-2.02; p = 0.001) and multivariable analyses (HR 1.36; 95% CI 1.03-1.79; p = 0.028). High-risk stage II AA patients had significantly worse 5-year OS compared to low-risk patients (67.1% vs. 74.5%, p = 0.0013). AC was administered in 34.4% (n = 166) of high-risk patients and in 36.5% (n = 203) of low-risk patients. Among high-risk patients, AC was not associated with better OS in univariate (HR 0.86; 95% CI 0.59-1.26; p = 0.722) and multivariable analyses (HR 1.35; 95% CI 0.90-2.04; p = 0.324) compared to no AC. Similarly, among low-risk patients, AC was not associated with better OS in univariate (HR 0.92; 95% CI 0.60-1.39; p = 0.813) and multivariable analyses (HR 1.27; 95% CI 0.81-2.02; p = 0.334) compared to no AC. For high-risk patients, 5-year OS was 68.3% in patients that received AC vs. 66.5% in patients that did not (p = 0.722). For low-risk patients, 5-year OS was 74.0% in patients that received AC vs. 76.3% in patients that did not (p = 0.813). Conclusions: High-risk stage II AA patients had significantly worse 5-year OS compared to low-risk patients. AC did not improve survival regardless of high risk features in stage II AA.
Diagnostic performance of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for the evaluation of hypermetabolic lymphadenopathy mediastinum lower, posterior, and middle, detected by PET-CT with 18F-FDG (PET) (APOGEE Study).
Authors: Bechade Dominique , Bellera Carine A. , Cantarel Coralie , Soubeyran Isabelle , Debled Marc , Chomy Francois , Roubaud Guilhem , Fonck Marianne , Cazeau Anne Laure
Published: February 2020

798

Background: In the context of a new cancer or relapse, the high sensitivity (Se) (95-100%) of PET-CT with 18F-FDG can lead to the demonstration of hypermetabolic mediastinal adenopathies. Its lower specificity (Sp) (89%) can require histological examination. We report the results of a prospective, single-center study evaluating the diagnostic performance of EUS-FNA in this indication. Methods: Prospective single-center study featuring patients in whom PET had revealed hypermetabolic mediastinal lymphadenopathy requiring diagnostic certainty. All EUS-FNA were performed with a 19-gauge needle (EchoTip, Cook Endoscopy). Main objective: To evaluate the diagnostic performance in terms of Se and Sp of EUS-FNA in the characterization of hypermetabolic mediastinal adenopathies in PET in the context of a new cancer or relapse. Secondary objectives: To evaluate the negative predictive value (NPV) of the EUS-FNA and to evaluate the percentage of surgical diagnostic procedures avoided. The standard technique was a thoraco-abdominopelvic CT scan at 6 months and at 12 months. Results: 52 patients were eligible and evaluable for the primary endpoint. The most common primary cancers were mammary (17.3%) and bronchial (13.5%). The lymph nodes were analyzed as malignant in 44.2% of cases, benign in 50% of cases and atypical or suspicious in 3.8% of cases. The malignant lymph nodes were metastatic for breast cancer in 21.7% of cases, bronchial cancer in 17.4% of cases, colorectal cancer in 17.4% of cases and prostate cancer in 13% of cases. The Se of the EUS-FNA was 92% (95% CI 0.74-0.99) and the Sp 100%. NPV was 87% (95% CI: 0.59-0.98). A diagnostic surgical procedure was necessary in 2% of the cases. PET and EUS-FNA often allowed the modification of the therapeutic strategy. Conclusions: When a confirmed diagnosis is required, the diagnostic accuracy of the minimally invasive procedure of EUS-FNA, is sufficiently robust to avoid a surgical diagnosis technique. The combination of PET and EUS-FNA may alter the therapeutic strategy that would have been considered after PET alone. Clinical trial information: NCT01892501.
Encyclopedic liquid biopsies for guideline-compliant diagnostic work-up in gastrointestinal cancers.
Authors: Patil Revati , Akolkar Dadasaheb , Patil Darshana , Limaye Sewanti , Page Raymond , Crook Timothy , Datta Vineet , Schuster Stefan , Sims Cynthe , Srivastava Navin , Devhare Pradip , Fulmali Pradip , Patil Sanket , Patel Shoeb , Fulmali Pooja , Khan Shabista , Chougule Rohit , Dhasarathan Raja , Srinivasan Ajay , Datar Rajan
Published: February 2020

799

Background: Definitive diagnosis of gastrointestinal (GI) malignancies is reliant on histopathological examination of tumor tissue obtained by invasive biopsies. However, invasive biopsies are associated with procedural risks, complications and expenses. A non-invasive technique for diagnosis of GI cancers is presently unavailable. Here we present a non-invasive diagnostic approach for GI cancers based on immunocytochemical (ICC) profiling of Circulating Tumor Associated Cells (C-TAC) enriched from peripheral blood. Methods: We collected 15 mL peripheral blood from 1052 patients with known diagnosis of Ca Oesophagus (244), Ca Stomach (170) and Ca Colorectum (638) and with histopathological information available from prior tissue analysis. CTACs were harvested following negative enrichment. C-TACs were identified by immunostaining with EpCAM and panCK. Deep ICC characterization was carried out in a subset of 203 samples (100 colorectal, 19 Gastric and 84 Esophageal) using organ specific markers. A subset of 19 samples from Gastric and 94 samples Esophageal cancers were profiled for Her2 and PD-L1 status. Results: C-TACs could be identified and enriched in 1012 out of 1052 patients (96.2% overall sensitivity). Immunostaining for organ-specific markers was possible in all 203 (100%) samples. Her2 positivity was observed in 2/19 Gastric and 19/84 Esophageal samples. PD-L1 (22C3) positivity was observed in 5/19 Gastric and 32/84 Esophageal samples while PD-L1 (28-8) positivity was observed in 2/19 Gastric and 16/84 Esophageal samples. Conclusions: Our results show that ICC profiling of C-TACs can provide necessary diagnostic information non-invasively to substitute conventional procedures dependent on tissue extraction. This approach fulfils most clinical decision-making requirements in GI malignancies.
Circulating ensembles of tumor-associated cells in gastrointestinal cancers.
Authors: Akolkar Dadasaheb , Patil Darshana , Page Raymond , Crook Timothy , Limaye Sewanti , Datta Vineet , Schuster Stefan , Fulmali Pradip , Fulmali Pooja , Srivastava Navin , Devhare Pradip , Apurwa Sachin , Patel Shoeb , Srinivasan Ajay , Datar Rajan
Published: February 2020

808

Background: CEA and CA19-9 are non-specific markers for Gastrointestinal (GI) cancers. Molecular analysis of fecal blood is of limited utility in colorectal cancers. A non-invasive pan-GI-cancer blood-based test with high specificity and sensitivity is an unmet medical need. Considering that unprovoked thromboembolism is a significant risk in multiple cancers, we hypothesized that circulating thrombotic emboli in peripheral blood could comprise cancer cells and would serve as a reliable biomarker for detection of GI cancers. Methods: We obtained 15ml of blood from 7481 individuals, including 181 cases of Esophageal cancer, 125 cases of Gastric cancer, 448 cases of colorectal cancer and from 6727 asymptomatic individuals with age related elevated risk who underwent evaluation of serum CA19-9 and AFP. Peripheral blood mononuclear cells (PBMC) were isolated by centrifugation and further processes for negative enrichment and harvesting of circulating tumor cell clusters which were characterized by immunostaining. Circulating Ensembles of Tumor Associated Cells (C-ETACs) were defined as clusters of 3 or more cells which were positive for EpCAM and CK, irrespective of CD45 status. Results: C-ETACs were detected in 86.7% of esophageal cancers, 94.4% of gastric cancers and 91.3% of colorectal cancers respectively irrespective of extent (stage / metastatic status) of disease and prior treatments. Overall sensitivity among 754 cancer patients was 90.7%. Among the asymptomatic individuals, C-ETACs were detected in 31 / 366 (8.5%) individuals with elevated CEA and 10 / 152 (6.2%) individuals with elevated CA19-9. C-ETACs were detected in 160 / 5333 (2.9%) of the asymptomatic individuals who had no abnormal findings in any of the said markers. Conclusions: C-ETACs were ubiquitously detected in cancers of Oesophagus, Stomach and Colorectum regardless of stage and treatment status, and pose significant latent risk of thromboembolism and metastasis/recurrence. The relative undetectability of C-ETACs in the asymptomatic cohort indicates causative connection with malignancies and are suitable for screening for these cancers.
Emergency department use at the end of life in elderly patients with gastrointestinal malignancies and mental health comorbidities.
Authors: Kashyap Mehr , Harris Jeremy Phillip , Chang Daniel Tandel , Pollom Erqi L.
Published: February 2020

811

Background: Aggressive care at the end-of-life can contradict patients’ wishes, negatively impact patient quality of life, and contribute to overall health care expenditures. Patients with mental disorders (MD) often experience disparities in medical care and have poorer clinical outcomes. We investigated the impact of mental disorders on emergency department (ED) use at the end of life among elderly patients with gastrointestinal (GI) malignancies. Methods: We conducted a retrospective cohort study using the SEER-Medicare database. We identified patients aged 66 years and older with GI malignancies (colorectal, pancreatic, gastric, hepatic, biliary, esophageal, small bowel, and anal cancer) diagnosed between 2004 and 2013 who had recorded death. We assessed the association between MD (depression, bipolar disorder, psychotic disorder, anxiety, dementia, and substance abuse) and ED use within 30 days of death using logistic regression models. Results: Of the 160,367 decedents included, 54,461 (34.1%) had at least one MD diagnosis between one year prior to cancer diagnosis and death. Those with MD were more likely to use the ED more than once in the last 30 days of life (14.7% vs. 12.4% p < 0.01). ED use was highest among decedents with anxiety disorder (15.8%) and substance abuse (16.3%). Among decedents with mental disorders, risk factors associated with ED use at end of life include being male (adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.10 – 1.22), younger (aOR 1.14, 95% CI 1.06 - 1.23), and black (aOR 1.33, 95% CI 1.23 – 1.45), living in a lower income zip code (1.21, 95% CI 1.13 – 1.30), and having a higher Charlson comorbidity score (aOR 1.71, 95% CI 1.56 – 1.87). ED use was also associated with pancreatic (aOR 1.16, 95% CI 1.08 - 1.25), hepatic (aOR 1.21, 95% CI 1.11 - 1.33), biliary (aOR 1.16, 95% CI 1.03 - 1.30) and esophageal (aOR 1.16, 95% CI 1.04 - 1.29) cancer compared to colorectal cancer. Conclusions: MD is associated with increased ED use at the end of life among elderly patients with GI cancer. Palliative and supportive care including mental health services early in the disease course may improve quality of end-of-life care in this vulnerable population.
Hospice length of service in patients with advanced gastrointestinal cancers treated at an NCI-designated cancer center.
Authors: Gupta Arjun , Sedhom Ramy , Middleton Emily , Cooper Rhonda , Knight Louise , Laheru Dan , Smith Thomas J.
Published: February 2020

812

Background: Hospice Length of service (LOS) is a Quality Oncology Practice Initiative (QOPI) measure, and an established metric of end-of-life (EOL) care. Short hospice LOS is associated with lower-quality EOL care, poor symptom control, and patient and caregiver dissatisfaction. Oncologist- and/ or system-specific factors may contribute to shorter hospice LOS. Methods: We conducted a retrospective chart review of patients with advanced gastrointestinal (GI) cancers referred to hospice from a comprehensive cancer center in 2018, and compared data to 2015. We analyzed LOS under hospice care, looking specifically at median LOS and percent of short enrollments (%LOS ≤ 7 days), and examined the variation between individual oncologists within the GI oncology division. The coefficient of variation (Cv) represents degree of variability between oncologists, and was calculated based on median LOS for each oncologist. Mean and SD of oncologist LOS were calculated. Cv was defined as SD/mean; Cv > 100% is typically considered a high variance distribution. Results: A total of 114 patients with advanced GI cancers were discharged to hospice in 2015, and 115 patients in 2018. The median age of patients was 66 years, 47% women, and 80% white. The number of GI oncologists were 9 in both years and median patients per oncologist were 12 in 2015, and 13 in 2018. The median hospice LOS was 16 days in 2015, which decreased to 9 days in 2018. The %LOS ≤ 7 days increased from 25% in 2015 to 47% in 2018. The Cv% was < 100% in both 2015 (63%) and 2018 (44%). Conclusions: In this retrospective study of hospice LOS among patients with advanced GI cancer at a single cancer center, median hospice LOS declined, and %LOS ≤ 7 days increased from 2015 to 2018. We did not find significant variation in hospice referral patterns between oncologists within the GI oncology division. These data point to system level factors responsible for sub-optimal hospice LOS. We will present our data at division meetings, and use mixed-methods design for investigating and eventually addressing barriers to low hospice LOS.
Implementation of an EMR integrated pathway for the management of malignant bowel obstruction.
Authors: Schuitevoerder Darryl , Vining Charles Christian , White Michael , Hoppenot Claire , Lazo Isabel , Sherman Scott K. , Kamm Alaine , Chavez Luz , Kallakuri Pujitha , Fenton Emily , Male Joshua , Tun Sandy , Ahmed Osmanuddin , Semrad Carol , Radovanovic Dragana , Eng Oliver , Micic Dejan , Lee Nita Karnik , Polite Blase N. , Turaga Kiran
Published: February 2020

813

Background: Despite published evidence based interventions for malignant bowel obstruction (MBO), implementation of a standard pathway is challenging. We hypothesized that using industrial engineering techniques and a modified dynamic sustainability framework for implementation, we can implement an electronic medical record (EMR) based pathway in the management of MBO. Methods: A workflow in the management of MBO was developed using iterative meetings from 8/2018 to 4/2019 including gateway stakeholders (surgical oncology, gynecological oncology and medical oncology), interventional stakeholders (gastroenterology, interventional radiology) and supportive stakeholders (hospital medicine, palliative care, nutrition, nursing). Industrial engineers were utilized to study human factors, and perform a method study. EMR integration was performed using EPIC systems Agile MD pathway and educational materials were created. Interventions such as early placement of gastrostomy tubes, total parenteral nutrition and medications were protocolized. Results: Since implementation, over 6 months the pathway and order set has been activated 56 times. Orders have been employed 21 times through the AgileMD pathway demonstrating a pathway drift of 62.5%. Educational materials have been accessed routinely during this time. Conclusions: Feasibility of implementing an EMR integrated MBO pathway is demonstrated with early suggestion of pathway drift. Utilizing tools of implementation science are necessary to facilitate widespread adoption of evidence based interventions in the management of patients with MBO.
A retrospective analysis of factors affecting palliative care consult in patients undergoing cytoreductive surgery and HIPEC.
Authors: Babar Laila , Lo Herman , Ashraf Obaid , Sethi Ashish , Alvi Zara , Finley Gene Grant , Monga Dulabh K. , Schiffman Suzanne , Raj Moses S.
Published: February 2020

815

Background: The National Cancer Institute defines palliative care as care given to improve the quality of life (QOL) for patients with life threatening diseases. The role of palliative care (PC) within oncology is ever evolving and as more studies are being conducted, its role in the improvement of QOL for patients is being widely recognized. Patients undergoing cytoreductive surgery (CRS) are at a higher risk for morbidity and mortality and often have severe post-operative symptoms that can worsen their QOL. Here we studied the factors affecting PC consult in order to better overcome them. Methods: We queried our Electronic Medical Record EPIC for a list of patients who underwent cytoreductive surgery with HIPEC or HITEC in the hospital from April 2016-April 2019. Data was manually extracted and patients who didn’t meet our criteria were excluded. Patients were divided on the basis of palliative care consults and differences between the groups were analyzed. Odds ratios(OR) with p-value 0.05 and confidence interval (CI) 95% were calculated. Results: We identified 55 patients of whom 34 met our inclusion criteria, 11 male and 23 female with an average age of 56.3 years at the time of diagnosis. 8 patients (23%) had PC; more than 1 comorbidity and age > 40 was associated with a higher likelihood of PC (OR:0.12; CI:0.02-0.76; p:0.02) and (OR: 0.015; CI: 0.0007-0.3029; P: 0.006) respectively. Gender, insurance type and marital status did not corelate with PC. Mean age (58.1 vs 55.7) showed a trend towards higher rates of PC in older population. Conclusions: Approximately one quarter of patients undergoing CRS with HIPEC had a concurrent PC consult. Though this is better than the national average of 11-16%, it continues to be a very small number. PC is not only an end of life service, in fact studies have shown early consultations lead to higher patient satisfaction, improved QOL and better communication. Efforts must be made to engage PC early in the course of treatment and recognize it as an integral part of cancer care.
Comparison of treatment plans feasible through AI enabled multidisciplinary online tumor board solution versus NCCN-based clinical decision support system (CDSS).
Authors: Sirohi Bhawna , Beriwal Sushil , Pramesh C. S. , Chopra Supriya , Goel Mahesh , Mathew Aju , Ostwal Vikas S. , Pandey Durgatosh , Rajagopalan Malolan Sri , Ramaswamy Anant , Sunil Bj , Badwe Rajendra A.
Published: February 2020

816

Background: Multidisciplinary tumor boards at Academic Medical Centers (AMC) maximize cancer outcomes. Guidelines based CDSS are alternatives to determine care pathways. Since 2015, 300 AMC cancer experts in USA and India use an AI enabled online tumor board solution, “NAVYA,” to scale low cost access to multidisciplinary expertise, on 1-2 minutes of expert time per decision (ASCO 2017). Methods: GI patients who used NAVYA between 5/1/15-8/31/19 were analyzed. Actionable treatment plans generated by NAVYA were compared to NCCN. Actionable treatment plans include chemotherapy protocols (doses, frequencies), radiation protocols (sites, fractions), etc. Inactionable specialty level decisions (CT-RT vs. surgery) lack specificity. Results: 1302 patients (4638 treatment decisions) were analyzed: 61% (794) male, 80% between age 45 to 75, mostly with Colon, Pancreas, Gallbladder, Rectum, or Stomach cancer; 49.7% non-metastatic. Cohort was comparable to GLOBOCAN estimates. In 82.2% (3812/4638) decisions, NAVYA added value beyond NCCN. First, in 4.5% (212/4638), NAVYA recommended a patient-specific treatment plan that was not part of NCCN. Second, in 3.2% (148/4638), NAVYA recommended treatments plan for clinical scenarios not covered by NCCN, (for eg. 3rd line therapies). Third, in 74.5% (3452/4638), NAVYA used patient specific criteria including resource constraints and patient preference to choose a treatment plan amongst the multiple pathways provided by NCCN and added actionable treatment details. Conclusions: Guideline based CDSS are insufficient to make the vast majority of actionable treatment decisions. Scaling rapid access to multidisciplinary experts is critical. Leapfrogging existing guidelines based CDSS, NAVYA online tumor board makes actionable expert treatment plans possible at a large scale.
The relationship between chemotherapy-induced peripheral neuropathy and heart rate variability.
Authors: Jang Aelee , Kim Dong Uk
Published: February 2020

820

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication related to chemotherapeutic agents and dose accumulation. Initial symptoms are known to be sensory including numbness and pain whereas autonomic symptoms are the latest. Autonomic dysfunction is related to heart rate variability (HRV) change which may precede the symptoms. But, the relationship between CIPN and heart rate variability is not fully evaluated. Therefore, we aimed to evaluate the HRV with CIPN-related questionnaires in patients underwent chemotherapy. Methods: Fifty-five patients with gastrointestinal cancers were enrolled in this cross-sectional cohort study. Patients have received chemotherapeutic agents such as paclitaxel, cisplatin, and oxaliplatin. CIPN was diagnosed using National Cancer Institute Common Toxicity Criteria for Adverse Event (NCI-CTCAE version 4.03). We evaluated the quality of life, CIPN symptom scale, and HRV. Results: Forty-two patients were male (76.4%) and mean age was 63.2 years old. Thirty-nine patients (71.0%) had CIPN of more than grade I according to NCI-CTCAE. Patients with CIPN represented lower physical and role functions. The standard deviation of all normal R-R intervals (SDNN) was decreased in the CIPN group. Parasympathetic tone (high frequency band) were decreased, but sympathetic activity (low frequency band/high frequency band) were increased in CIPN. Conclusions: CIPN affected the quality of life in gastrointestinal cancer patients underwent chemotherapy. HRV was related to CIPN. Further study may be needed to check the feasibility of HRV as early biomarkers for detecting CIPN.

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Feasibility of endoscopic resection in gastric gastrointestinal stromal tumor.
Authors: Kim Yuri , Jung Hwoon-Yong , Kim Do Hoon , Lee Jeong Hoon , Choi Kee Don , Ahn Ji Yong , Na Hee Kyong , Park Young Soo
Published: February 2020

822

Background: Endoscopic resection (ER) can be applied for small SETs of stomach. GISTs can be diagnosed pathologically after resection. Initially we used ESD. Submucosal tunneling endoscopic resection (STER) was introduced for overcoming limitations of ESD. However, STER was very difficult to apply for gastric lesions. We developed new ER method, clip-assisted surgical endoscopy (CASE, Jung's method). In this study, we evaluate the feasibility of ER for GISTs and compared 3 ER methods. Methods: Medical records of 53 patients who diagnosed GISTs after ER for SETs from 2005 to 2019 were reviewed retrospectively. Average age was 60.0 ± 10.6 years. ESD, STER and CASE were performed for 23, 5, and 25 patients, respectively. Clinical characteristics, procedure times, and outcomes of each endoscopic technique were analyzed. Results: Average pathological size of GIST was 2.1 cm. 94.3% proved to be very low risk of malignant potential. Location of SETs were different; ESD applied mainly for body lesions, STER tried for fundus lesions, CASE also mainly for fundus and high body lesions. Overall R0 and R1 resection rate was 62.3%, and 35.8%. There are 34 patients who had complications after the procedure (21 micro-perforation, 12 macro-perforation, 1 bleeding), but perforation would be a part of ER procedure for SETs. In ESD, some macro-perforations was a reason for surgical conversion. Four patients (2 ESD, 1 STER, 1 CASE) underwent surgical conversion during ER. STER had the longest procedure time (50.3, 95.2 and 40.7 min, P = 0.018). After development of CASE procedure, we can reduce procedure time and on-site surgical conversion. R0 resection rate was highest in CASE. No R1 resected patients were recurrent so far. Conclusions: ER seems to be safe and effective therapeutic options for removing small gastric GISTs. Using CASE (Jung's method), ER would be more comfortable especially in the fundus lesions.
Regorafenib as second-line therapy for imatinib-resistant gastrointestinal stromal tumor (GIST).
Authors: Takahashi Tsuyoshi , Nishida Toshirou , Kudo Toshihiro , Boku Narikazu , Honma Yoshitaka , Komatsu Yoshito , Nakatsumi Hiroshi , Matsumoto Koji , Onoe Takuma , Oki Eiji , Nakamoto Masako , Fukutani Miki , Nomura Shogo , Sato Akihiro , Naito Yoichi , Doi Toshihiko
Published: February 2020

823

Background: Imatinib is a standard first line treatment for advanced gastrointestinal stromal tumor (GIST); however eventually almost all the GISTs become resistant to imatinib. Secondary mutation in KIT is the most relevant cause of imatinib-resistant, as high as 70% of cases. Sunitinib is standard of care for imatinib-resistant GIST with median progression-free survival (PFS) of 24.6 weeks; however, in a preclinical study sunitinib is not active for approximately half of secondary mutations. Regorafenib is active for some secondary mutations resistant to sunitinib in the preclinical study. Therefore, we conducted a phase II study evaluating regorafenib for imatinib-resistant GIST. Methods: Patients with imatinib-resistant advanced GIST were enrolled. Key eligibility criteria were ECOG PS of 0-1 and adequate organ function. Prior exposure of sunitinib was not allowed. The primary endpoint was PFS rate at 24 weeks. ctDNA for KIT was evaluated prior to regorafenib administration. Results: A total of 38 patients were enrolled as planned. Median age was 64.5 (39 - 80). Twenty-five patients were male. Primary site was stomach in 17, small intestine in 16. Median PFS was 36.3 weeks and PFS rate at 24 weeks was 47.4% (primary endpoint was not met). Best overall response was PR for 6 (16 %), SD for 25 (63 %) and PD for 5 (13 %) patients. Grade 3 or more adverse events (AE) were observed in 25 (66 %) patients. Common grade 3 or more AE were hand-foot-skin reaction (n = 9), hypertension (n = 9), hepatotoxicity (n = 4). ctDNA was evaluated in 32 patients and among them secondary mutations were observed in 15 patients (47%). PFS was shorter (15.6 weeks) in patients with exon 13 mutation than that in patients without second mutation (49.3 weeks, not statistically significant). Conclusions: Regorafenib demonstrated favorable activity in patients with imatinib-resistant GIST as second line therapy with acceptable toxicity. Secondary mutation in KIT might be a predictor of the efficacy of regorafenib. Clinical trial information: UMIN000016115.