bluuebunny/crossref_metadata_2025 huggingface dataset:
Time from first symptoms to diagnosis in GEP-NET patients: Results from a large German tertiary referral center.
Authors: Koca Esra , Koch Christine , Husmann Gabriele , Bojunga Jörg
Published: February 2020

610

Background: Patients with neuroendocrine tumors (NET) often go through a long phase between onset of symptoms and initial diagnosis. Methods: Retrospective analysis of 486 patients with GEP-NET (488 tumors) at tertiary referral center from 1984-2019; inclusion criteria: Patients > 18 years, diagnosis of GEP-NET; descriptive analysis using SPSS; Cox regression, Log rank test. Results: Demographics: Male 54% / 52.9% (all/GEP-NET), median age at first diagnosis 63y/58y (all /GEP-NET). Localizations: small intestine 145/488 (29.7%), pancreas 143/488 (29.3%), CUP 53/488 (10.9%), colon 49/488 (10%), stomach 45/488 (9.2%), rectum 27/488 (5.5%), other digestive organs 11/488 (2.3%), esophagus 5/488 (1%), other 10/488 (2%). Ki67 in 330/488 (67.6%) evaluable patients: < 3%: 155/330; 46.9%; ≥ 3%: 111/330; 33.6%; > 20%: 64/330;19.3%. 128/488 (26.2%) of patients had NET specific symptoms (abdominal pain 77/128; 60.2%, diarrhea 51/128; 39.8%, flush 19/128; 14.8%, carcinoid syndrome 8/128; 6.3% tachycardia 6/128; 4.7%). 122/488 (25%) patients showed other tumor-specific symptoms (weight loss 48/122; 39.3%, stool irregularity 21/122; 17.2%, hypoglycemia 10/122; 8.2%, painless jaundice 8/122; 6.6%). 154/ 488 (32%) of NET were incidental findings (imaging 39.6%, endoscopy 23.4%, surgery for other causes 18.8%, appendectomy 15.6%). 221/279 (initial diagnosis/any time; 79.2%) patients had distant metastases at initial diagnosis (187/221 liver metastases). Time from tumor manifestation to initial diagnosis: pNET 360 ± 116 days, siNET 309 ± 87 days, gastric NET 66 ± 47 days, colonic NET 98 ± 67 days. Time from onset of symptoms to diagnosis in symptomatic patients was significantly longer than in asymptomatic patients (388 ± 86 days vs. 174 ± 58 days, p = 0.001). No significant difference in patients with or without distant metastases (223 ± 78 days vs. 259 ± 57 days, p = 0.355). Conclusions: A large proportion of NET are incidental findings and only about half of all patients are symptomatic at the time of diagnosis. Diagnosis for symptomatic patients takes significantly longer than for asymptomatic, which might be due to mainly unspecific symptoms. Presence of metastases has no influence on time to diagnosis.
Usefulness and applicability of next generation sequencing in neuroendocrine neoplasms.
Authors: Manyanont Sorrapong , Winter Kyle , Trikalinos Nikolaos
Published: February 2020

626

Background: Neuroendocrine neoplasms (NENs) are rare tumors that can arise anywhere in the body and treatment options are limited due to their rarity. Knowledge of their mutational status might allow for tumor agnostic treatments or aid in enrollment in clinical trials, especially in the metastatic setting. Methods: Eligible NEN patients on an institutional, IRB approved protocol, who had NGS as standard of care and were treated in the past 24 months were included. Tumors were categorized by location and histologic grade. We explored the actual and theoretical eligibility for tumor agnostic treatments and enrollment in clinical trials as available on clinicaltrials.gov. Results: Between August 2017 and July 2019 a total of 107 patients were eligible. Globally 102 clinical trials included patients with NEN and specific mutations.NGS detected one (1%) case of MSI high and one (1) TRK fusion positive tumor, eligible for checkpoint inhibitor and TRK inhibitor therapy respectively. Moreover, NGS identified 16 (15%) cases of MEN1, 1 (1%) of RET, 2 (2%) of NF1 and 3 (2.8%) of MUTYH, 2 (2%) TSC or TSC2, BRCA in 1(1%). These patients were appropriately referred to genetic counseling. About 51.5% of patients would in theory be eligible for an investigational treatment based on mutations and clinical trial availability. Fifty two of 107 patients (48.5%) would not have been eligible for a clinical trial with reasons varying between no mutations (24%), sample failure (8.4%) or nonactionable mutations (15.9%). Conclusions: NGS can point to clinical trial eligibility and guide genetic counseling and should probably be a standard approach in the evaluation of new metastatic NEN patients.
Out-of-pocket spending (OOPS) and financial toxicity survey for neuroendocrine tumor (NET) patients.
Authors: Chauhan Aman , Agrawal Rohitashva , Edwins Rebecca , Wahmann Maryann , Wahmann Bob , Corum Lauren , Anthony Lowell Brian
Published: February 2020

632

Background: Incidence and prevalence of neuroendocrine tumors (NETs) are on the rise. However, with the increasing burden of the disease, there is a need to understand financial toxicity associated with NET management. Especially the out of pocket spending or expenses made by patients and family members, which affects the management and treatment adherence. We report results of our prospective online survey based study looking into determinants and the burden of financial toxicity in NET patients. Methods: We collaborated with NCAN (Neuroendocrine Cancer Awareness Network) a national NET patient support group for our prospective online questionnaire-based survey. After IRB approval, NCAN disseminated online link to the survey on their webpage. The survey had twenty-one questions with the goal of at least 200 complete responses. Results: We received 215 responses before we decided to stop the survey for analysis. The average age of the respondents was 58.4 years. 75% of respondents were females with most repsondents of the survey (37%) being graduates. About 41% of respondents had small bowel NET while 27% had pancreas NET as their NET diagnosis. The median income of the respondents was $65000/year. Median oncology visits were reported to be 4 per year. Median co-pay for the NET specialist visit was found to be $30. The median spending on travel for the physician`s appointment was $250 per visit to see NET specialists. Median monthly insurance premium was $300. Study participants reported spending $75 out of pocket on NET related care every month on top of insurance premiums. More than half of the respondents were on Somatostatin analogues only as their main treatment. About 21% mentioned that they were not able to get required treatment due to cost related issues. Conclusions: The preliminary analysis of the survey gave us an insight into financial toxicity related to NET management. Although most NETs are indolent, the chronic nature of disease and associated, symptom management is often time and resource-intensive. Many patients mentioned having issues with the coverage of insurance and having to travel a long distance to see a NET specialist, which demonstrate a lack of access to NET specialists.
Mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) of gastrointestinal (GI) tract: A single institution experience.
Authors: Amin Manik A. , Trikalinos Nikolaos
Published: February 2020

633

Background: MiNENs are heterogeneous group of rare tumors and represent less than 1% of all GI malignancies. These are pathologically classifiable according to neuroendocrine component into low grade, intermediate grade and high grade MiNENs but and managed based upon non-neuroendocrine component rather than true NENs. They have poor prognosis and less is known about treatment options. Methods: We identified 34 cases of MiNENs from 1/1/2000 to 1/1/2018 from Siteman Cancer Registry Database at Siteman Cancer Center, Washington University, St. Louis. Treatment and follow up information was obtained from medical charts of patients. Results: Of 34 identified cases of MiNENs, our database showed equal distribution of MiNENs in male and female patients (N = 17 each). Site of origin included appendix (N = 14), colon (N = 10), esophageal (N = 2), stomach (N = 3), rectum (N = 3), small intestine (N = 1) and ampulla of Vater (N = 1) locations. Histology was high grade (N = 22), intermediate grade (N = 8), low grade (N = 3) and unknown (1). Twenty nine (85%) underwent surgical resection with curative intent and 13 (40%) patients were disease free at five years of follow up. Disease was localized in 15 patients (44%) and distant metastasis were reported in 13 patients (40%). Ten out of 15 patient with localized disease were disease free with combined modality therapy of surgery and chemotherapy. Most common chemotherapy regimen used in the metastatic setting was FOLFOX (11), 5FU/capecitabine (3), and carboplatin plus etoposide (5). Next generation sequencing analysis was available on limited patients which showed MMR proficient (3), MMR deficiency (1), BRAF V600E mutation (1) and KRAS wild type (1). Conclusions: MiNENs of GI tract are rare and aggressive tumors and represent a distinct entity. Surgical resection whenever possible offers curative option. Our database of GI MiNENs showed efficacy with commonly used GI chemotherapy regimens. Patients with low grade tumor histology had better survival as compared to moderately and poorly differentiated tumors. Genomic testing through NGS would be recommended for personalized treatment decisions given poor prognosis in these patients.
Metachronous colorectal pathology among survivors of young-onset colorectal cancer: Implications for postresection colonoscopic surveillance.
Authors: Peacock Oliver , Yang Yun , Thirumurthi Selvi , Nguyen Sa Thi Nguyen , Lum Phillip , Rodriguez-Bigas Miguel A. , Bednarski Brian K. , Messick Craig , Skibber John Michael , Chang George J. , Vilar Sanchez Eduardo , You Y. Nancy
Published: February 2020

64

Background: Patients with sporadic young-onset colorectal cancer (CRC) are postulated to have a more biologically active colorectum prone to malignant transformation earlier in life. It is unknown whether there is elevated risk for metachronous colorectal pathology after the index cancer. We aimed to define this risk, to inform their post-resection endoscopic surveillance. Methods: Consecutive CRC patients (aged 18-50, n = 728) were prospectively followed after surgical resection between 2009 and 2017. Patients presenting with hereditary CRC, recurrent disease, or without endoscopy follow-up were excluded. All endoscopy records were subjected to natural language processing and further reviewed. Metachronous colorectal pathology of interest included: high-risk adenoma (≥1cm in size, > 3 in number, or tubulovillious/high-grade dysplasia histology), second CRC, and endoscopically detectable local recurrence. Results: During a 48-month (median) follow-up, 457 patients underwent 1,192 person-years of colonoscopic follow-up. The median age at CRC diagnosis was 44 years. Disease arose from the proximal colon in 9.4%, distal colon in 23.0% and rectum in 67.6%, and was stages I/II in 191 (41.8%), III in 185 (40.4%), and IV in 81 (17.7%). The majority (95.8%) underwent segmental resection, while the remainder had extended resections for synchronous pathology not amendable to preoperative endoscopic clearance. The overall incidence of metachronous pathology was 32 per 1000 person-years: 31 patients developed high-risk adenomas (6.8%), 1 had a second CRC (0.2%), and 7 had luminal recurrences (1.5%). The median time to metachronous pathology was 13.9 (IQR: 11.8-33.1) months, with 21 (53.8%) detected between 12 and 48 months post-resection. Conclusions: For young-onset CRC survivors, the incidence of metachronous colorectal pathology was 32 per 1000 person-years of follow-up. Given the time pattern of detection, adding an interval colonoscopy between the current recommended post-resection surveillance at 12 and 48 months may be beneficial.

[Table: see text]
Pathological examination of CT findings of tumor infiltration to the periarterial plexus in pancreatic cancer.
Authors: Miyamoto Takashi , Yamamoto Yusuke , Sugiura Teiichi , Okamura Yukiyasu , Ito Takaaki , Ashida Ryo , Ohgi Katsuhisa , Uesaka Katsuhiko
Published: February 2020

644

Background: The radiographic diagnosis of tumor infiltration into the periarterial plexus in pancreatic cancer is important because it is related to the classification, however, it is difficult to distinguish the abnormal shadow along the artery caused by inflammation or cancer infiltration. The aim of this study is to investigate CT values of the abnormal shadow along artery could distinguish between inflammation and tumor invasion. Methods: Study 1: Of 26 patients who underwent DP-CAR between 2009 and 2018, we analyzed 19 patients who had dynamic CT and obtained sagittal slice taken 120 seconds after injection with less than 2.5 mm slice thickness. At first, we measured CT values at upper and lower point of CeA and CHA each sagittal slice using CT. Next, we evaluated tumor invasion at the upper and lower plexus of CeA and CHA in each section of the pathological specimen, and evaluated the relationship between the tumor invasion and the CT value. Study 2: Using these 19 patients and 40 patients who underwent DP for PDAC between 2010 and 2014, we analyzed the relation between CT value and long-term states. Results: Study 1: CT value was totally measured at the 606 points using 19 patients who underwent DP-CAR. At the 490 points, we did not observe cancer infiltration and fibrosis. At the 70 points, we observed fibrosis without cancer cells. At the 46 points, we observed cancer infiltration. CT value was significantly higher in the tumor infiltration group than that in the without cancer infiltration and fibrosis group (P < 0.01). Study 2: The best cut-off of CT value of the presence of cancer infiltration was 44.9 HU using ROC curve (AUC = 0.861). The median survival time of patients who had the points of CT value > 44.9 HU around arteries was significantly shorter than that of patients who did not have the points of CT value > 44.9 HU (2.17 vs. 4.55 years, p = 0.03). Conclusions: The CT value around the arteries was significantly higher in the points of pathological tumor infiltration than that in the points of fibrosis without cancer cells. The best cut-off CT value of the presence of cancer infiltration around arteries was 44.9 HU, and the presence of the point of CT value > 44.9 HU around arteries was associated with poor survival.
Efficacy of chemotherapy for patients with unresectable or recurrent pancreatic adenosquamous carcinoma: A multicenter retrospective analysis.
Authors: Yoshida Yukio , Fukutomi Akira , Ueno Makoto , Mori Keita , Watanabe Kazuo , Ohba Akihiro , Kobayashi Satoshi , Furuta Mitsuhiro , Tsujimoto Akiko , Osaka Masato , Okano Naohiro , Yane Kei , Umemoto Kumiko , Kawamoto Yasuyuki , Terashima Takeshi , Tsumura Hidetaka , Doi Keitaro , Shioji Kazuhiko , Asagi Akinori , Furuse Junji
Published: February 2020

647

Background: Pancreatic adenosquamous carcinoma (PASC) is a rare variant of pancreatic ductal adenocarcinoma (PDAC). Although unresectable or recurrent PASC is usually treated by systemic chemotherapy, there are few reports which show the efficacy of chemotherapy. The aim of this study was to evaluate the efficacy of chemotherapy for patients (pts) with unresectable or recurrent PASC. Methods: We collected data retrospectively from 24 Japanese institutions. The selection criteria were as follows: 1) histologically or cytologically proven PASC (non-surgical specimens were eligible if squamous cell carcinoma (SCC) was detected), 2) unresectable or recurrent disease treated with 1st line chemotherapy between April 2001 and December 2017. Results: This study included 138 pts with median age of 66 years (range: 36-85). About 60% of pts were diagnosed with biopsy and only SCC was detected in 13.0% of pts. Median overall survival (mOS) was 6.7 months (M), median progression free survival (mPFS) was 2.8 M, and the 1-year survival rate (1YSR) was 26.7%. For the 102 metastatic or distal recurrent pts with PS of 0-1, patient characteristics were as follows: ≥76 years old, 9 (8.8%); PS of 0, 39 (38.2%); number of metastatic sites ≥2, 25 (24.5%). The treatment efficacies (The objective response rates(%)/mPFS(M)/mOS(M)/1YSR(%)) of the 5 major regimens were Gemcitabine(GEM) (n=45, 4.4%/2.2M/4.8M/28.1%), GEM+nab-PTX (n=24, 29.2%/2.9M/7.6M/23.1%), GEM+S-1 (n=9, 11.1%/5.1M/9.9M/25.4%), FOLFIRINOX (n=7, 14.3%/2.5M/7.5M/14.3%), and S-1 (n=7; 28.6%/2.6M/5.0M/28.6%), respectively. One patient with liver metastasis underwent conversion surgery after GEM+nab-PTX and achieved long survival. CRP ≥3.0mg/dl, CA19-9 ≥1000 U/ml, residual primary site, and monotherapy had a significant correlation with poor survival in multivariate analysis. Conclusions: Although combination chemotherapy regimens such as FOLFIRINOX and GEM+nab-PTX are now available, the prognosis of metastatic PASC remains poor. Development of more effective treatment options is required.
Scoring model with serum albumin and CA19-9 in advanced pancreatic cancer in second-line treatment: Results from the NAPOLEON study.
Authors: Komori Azusa , Otsu Satoshi , Shimokawa Mototsugu , Otsuka Taiga , Koga Futa , Ueda Yujiro , Nakazawa Junichi , Arima Shiho , Fukahori Masaru , Okabe Yoshinobu , Makiyama Akitaka , Taguchi Hiroki , Honda Takuya , Shibuki Taro , Nio Kenta , Ide Yasushi , Ureshino Norio , Shirakawa Tsuyoshi , Mitsugi Kenji
Published: February 2020

649

Background: Patients with metastatic pancreatic cancer refractory to first-line chemotherapy (CTx) have limited treatment options. Moreover, it is unclear what kind of patients could be brought about survival benefit by 2nd-line CTx after refractory to gemcitabine+ nab-PTX (GnP) or FOLFIRINOX. Methods: This analysis was performed as part of a multicenter retrospective study of GnP or FOLFIRINOX in patients with unresectable pancreatic cancer (NAPOLEON study) conducted by 14 centers in Japan. From December 2013 to March 2017, 255 patients with advanced or recurrent pancreatic cancer received GnP or FOLFIRINOX as 1st-line CTx. Excluding censored cases in first-line treatment, 156 and 77 patientsreceived 2nd-line CTx and best supportive care (BSC), respectively. Variables at the refractory or intolerant to the 1st-line treatment were used to investigate correlation with prognosis by Cox regression model. Then, we made scoring system using the prognostic factors to reveal the benefit of 2nd-line CTx. Results: Median post-progression survivals (PPSs) were 5.2 months in 2nd-line CTx group and 2.7 months in BSC group, respectively (hazard ratio [HR]; 0.42, 95% confidence interval [CI]; 0.31-0.57, p<0.01). According to the Cox regression model, serum Alb level of less than 3.5 g/dL (HR; 1.98, 95% CI; 1.33–2.96, p<0.01) and CA19-9 level of greater than 1,000 U/mL (HR; 1.87, 95% CI; 1.25–2.80, p<0.01) were independent predictive factors. The scoring system for PPS was designed using these factors, which was obtained by summing up serum Alb (≥ and < 3.5 g/dL allocated to scores 0 and 1) and CA19-9 (< and ≥ 1,000 U/mL allocated to scores 0 and 1) at disease progression in patients with 2nd-line CTx group. Patients with score 0 and 1 displayed significantly favorable PPSs in comparison with BSC group; however, there was no significant difference in PPS between patients with score 2 and BSC group (Table). Conclusions: Survival benefit of 2nd-line CTx was observed in patients with the score 0 and 1, but not in the score 2. [Table: see text]
Prognostic factors associated with short-term survival (STS) in advanced pancreatic cancer (APC): A multicenter analysis from the CHORD consortium.
Authors: Mehta Sakshi , Cardoso Miguel , Kim Christina , Armstrong Dawn Elizabeth , Ramjeesingh Ravi , Renouf Daniel John , Ahmed Shahid , Ko Yoo-Joung , Harb Mohammed , Kong Shiying , Cheung Winson Y. , Meyers Brandon M.
Published: February 2020

650

Background: The survival of patients (pts) with APC (locally advanced/metastatic) is slowly improving; however, in some pts it remains extremely short. Few studies have evaluated the clinical, pathologic and treatment characteristics associated with STS in APC. Methods: Pts with APC (between 2011-2017) were included in the analysis. Descriptive analyses were conducted for demographic, tumor and treatment characteristics between pts who survived ≤ and > 90 days using Wilcoxon rank-sum test and Chi-square test for continuous and categorical variables respectively. Multivariable logistic regression was performed to identify association between pts’ characteristics and STS. Results: A total of 580 pts were included in the analysis: median age 68, 53% male, 92% metastatic and 53% ECOG 0/1. STS ≤90 days occurred in 152 pts (26.2%), with 65.1% not receiving any chemotherapy. Median overall survival for STS was 49 days vs. 276 for non-STS. At least 1 cycle of chemotherapy was administered to 358 pts; mean duration of first-line chemotherapy for pts with STS ≤90 was 1.5(SD 2.5) cycles (N=53), compared to 7.6(SD 11.1) cycles (N=305) for pts surviving > 90 days. Prognostic factors associated with STS <90 days were neutrophil:lymphocyte ratio, LDH, metastatic disease, ECOG and not receiving chemotherapy (Table). Other clinical factors (BMI, smoking history, diabetes) and laboratory values (platelet, baseline CA19-9, estimated GFR) were not prognostic. Conclusions: In a multicenter database of Canadian academic centers, <2/3 of pts received at least 1 cycle of chemotherapy. Prognostic factors associated with STS include routine laboratory values, not receiving chemotherapy, ECOG and the presence of metastatic disease. Further evaluation of factors related to not receiving chemotherapy, and why chemotherapy is discontinued could improve the outcomes of pts with STS. [Table: see text]
Clinical outcomes of FOLFIRINOX and gemcitabine-nab-paclitaxel for metastatic pancreatic cancer in the real-world setting.
Authors: Franco Fabio , Martin Valades Jose Ignacio , Marrupe David , Camara Juan Carlos , Gutierrez Abad David , Lopez-Alfonso Ana , Martinez-Amores Brezo , Leon Ana , Perez Mar , Juez Ignacio , Hurtado Alicia , Ruiz-Casado Ana
Published: February 2020

656

Background: Randomized clinical trials have established new chemotherapeutic standards of care for metastatic pancreatic cancer, namely FOLFIRINOX (FFX) and gemcitabine + nab-paclitaxel (GNP) after demonstrating a significant and relevant increase of overall survival. However, there are some important uncertainties regarding how many patients are candidate to each of the two new regimens in the real life and how is the pattern of use in the elderly population. Methods: This is a retrospective study. Departments of Pharmacy of 7 Spanish hospitals generated the listings of patients (pts) treated in first line with these new regimens (FFX or GNP). Non-metastatic patients were excluded. An exploratory analysis was performed in the elderly population. Results: From Jan 2012 to Dec 2017, a total of 119 pts (M/F 58/42 %) were treated. Med age 63 y (38-83 y), 99% adenocarcinoma. 40% located in the head of pancreas. ECOG 87% 0-1. 89% had liver mets. In the 1st line 49.6% were treated with FFX and 50.4% with GNP. 53% of the pts could receive a 2nd line (82% after FFX 75% after GNP). The median OS was 12 months with no statistically significant differences between both regimens (12,7m for FFX vs 10,2 m for GNP). Elevated Ca 19.9 levels and Neutrophil-Lymphocyte ratio (NLR) increased the risk of death. Patients who received both regimens in first/second line had a median OS longer than 15 months whichever the sequence. 32 patients (27%) were older than 70 yo. 13 (41%) were treated with FFX and 19 (59%) with GNP. The median OS for patients older than 70 was 9.5m versus 12.3m for patients younger than 70. Conclusions: In our setting the use of FFX and GNP for treating metastatic pancreatic cancer is quite similar. Superiority could not be demonstrated for any of the schemes in first-line. Overall survival was determined by basal Ca 19.9 and NLR. Patients receiving both regimens (FFX or GNP) in first/second line whichever the sequence, exhibited the best survival rates. In our series elderly patients had poor survival rates.
Efficacy of second-line chemotherapy after standard combination chemotherapy in patients with metastatic pancreatic cancer: The results from the NAPOLEON study.
Authors: Fukahori Masaru , Okabe Yoshinobu , Shimokawa Mototsugu , Otsuka Taiga , Koga Futa , Ueda Yujiro , Nakazawa Junichi , Komori Azusa , Arima Shiho , Makiyama Akitaka , Taguchi Hiroki , Honda Takuya , Ushijima Tomoyuki , Miwa Keisuke , Shibuki Taro , Nio Kenta , Ide Yasushi , Ureshino Norio , Mitsugi Kenji , Shirakawa Tsuyoshi
Published: February 2020

661

Background: Gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX) have been established as standard first-line combination chemotherapy (CTx) for patients with metastatic pancreatic cancer (MPC). However, the efficacy of second-line CTx and the significance of combination CTx in clinical practice are unclear. We therefore investigated the efficacy of second-line CTx in patients with MPC. Methods: Data were collected from CTx-naive MPC patients treated with first-line combination CTx at 14 hospitals in the Kyushu area of Japan from December 2013 to June 2018. The median overall survival (mOS) from second-line treatment was compared between patients who received second-line CTx (CT group) and those who received best supportive care (BSC group). Furthermore, in the CT group, the mOS was compared between the patients who received combination CTx and those who received mono-CTx. To control potential bias in the selection of second-line treatment, we also conducted a propensity score-adjusted analysis. Results: A total of 255 patients received GnP or FFX as first-line CTx. Of these, there were 156 (61%) in the CT group and 77 (30%) in the BSC group. The number of patients who received FFX/GnP as first-line CTx was 79 (51%)/77 (49%) in the CT group and 15 (20%)/62 (80%) in the BSC group, respectively (P < 0.01). The mOS in the CT group was significantly longer than that in the BSC group (5.2 vs. 2.7 months; hazard ratio [HR] 0.42; 95% confidence interval [CI] 0.31-0.57; p < 0.01 and 5.2 vs. 2.6 months; adjusted HR 0.39; 95% CI 0.28-0.55; p < 0.01). In the CT group, 89 (57%) patients received combination CTx, and 67 (43%) received mono-CTx. There was no significant difference in the mOS between the combination CTx and mono-CTx patients (5.5 vs. 4.4 months; HR 0.88; 95% CI 0.62-1.26; p = 0.88 and 5.6 vs. 4.4 months; adjusted HR 0.85; 95% CI 0.56-1.30; p = 0.47). Conclusions: Among patients with MPC receiving second-line treatment, the CT group had a significantly longer mOS than the BSC group, but combination CTx conferred no improvement in the survival duration compared with mono-CTx.
A real-world evidence analysis of periampullary cancers in an academic hospital in Chile.
Authors: Villanueva Luis , Navarrete Gonzalo , Gallegos Ivan , Castillo Valentina , Dodds Francisco , Gonzalez Jaime , Barajas Olga , Vasquez Rodrigo , Nuñez Barbara , Ahumada Monica
Published: February 2020

663

Background: Periampullary cancers can originate in the pancreas, duodenum, bile duct or structures of the ampullary complex. The treatment of choice in early stages is pancreatoduodenectomy. The management post-surgery can depend on the histology pattern, and the overall survival can vary in different subgroups. Methods: A retrospective cohort study. We examined patients (pts) with invasive periampullary cancer undergoing pancreatoduodenectomy at the Hospital Clinico Universidad de Chile between 2002 to 2018. We analyzed epidemiological, clinical, surgical, and histological data. OS and the hazard ratio (HR) were established by GraphPad Prism 8.0. Results: Thirty-seven cases were registered. Twenty-two (59%) pts were men. The mean age was 62.5 (43-83 years). The histological subtypes were: 15 pts (40.5%) intestinal group (IN), 20 pts (54%) pancreatobiliary group (PB), 1 pt (2.7%) mixed and 1 pt (2.7%) signet ring cell type. A full concordance between histology and immunohistochemistry (CK20, CK7, CDX2, MUC1, and MUC2) patterns was 66% of the PB group, and 0% of the IN group. The stage IB was most frequent in all of the group (36,4%). The most frequent stages were IB (66,6%) in the IN type and IIIA (46%) in the PB type. The level of Ca19-9 was higher the PB group than IN group (629.7 versus 41.5 U/ml, respectively). Seven pts received postoperative adjuvant treatment such as FOLFOX, capecitabine, and gemcitabine. The median OS was 133,5 months (mo) in the intestinal group and 32,6 mo in PB group (P-value = 0.021). The HR was 0.38 (95% CI of ratio 0.1332 to 1.084). The 5-year OS was 75,2% and 45,7% in the IN and PB group, respectively. Conclusions: Periampullary cancer remains very challenging because it is a rare malignancy and present diverse histological pattern. These factors influence the behavior and OS of the disease. Our results showed clinically and statistically relevant differences in the staging, levels of Ca19-9, and OS of the IN and PB subtypes. Our patients received few post-operatory therapies such as chemotherapy; this factor could influence the OS in the high-risk group. According to our data, a personalized treatment by histological type should consider in this disease.
Long-term outcome after combined carbon-ion radiotherapy and chemotherapy for locally advanced pancreatic cancer.
Authors: Shinoto Makoto , Hirata Hidenari , Suefuji Hiroaki , Toyama Shingo , Ueda Minoru
Published: February 2020

671

Background: Carbon-ion radiotherapy (C-ion RT) has the potential advantages in terms of improved dose localization and enhanced biological effectiveness compared to conventional radiotherapy or proton therapy. C-ion RT is expected to contribute to the prolongation of survival in patients with pancreatic ductal adenocarcinoma (PDAC). We started C-ion RT for pancreatic cancer at SAGA HIMAT since April 2014. The aim of this study is to evaluate the long-term clinical results of C-ion RT for locally advanced PDAC. Methods: From April 2014 to March 2018, 144 patients with pancreatic cancer were treated with definitive C-ion RT. 80 patients who were confirmed as unresectable locally advanced PDAC were included in this retrospective analysis. C-ion RT was performed with 55.2 Gy (RBE) at 12 fractions in 3 weeks. Overall survival (OS) and prognostic factors were analyzed. Toxicities were evaluated using the CTCAE ver. 5.0. Results: The median follow-up period for survivors was 38 (range 13-59) months from the initiation of C-ion RT. In all patients, planned C-ion RT was completed. Induction chemotherapy was performed in 64 patients (80%) and the median duration time was 3 (range 1-19) months. Seventy patients (86%) underwent concurrent chemotherapy with gemcitabine or S-1. 2y-, 3y-, and 4y-OS from C-ion RT were 47% (95%CI, 37-59%), 25% (95%CI,16-37%), and 18% (95%CI, 10-30%), respectively. 2y-, 3y-, and 4y-OS from initial treatment were 55% (95%CI, 45-66%), 33% (95%CI, 24-45%), and 20% (95%CI, 12-32%). Multivariate analysis showed that PS 1-2, CA19-9 ≥350, and the absence of concurrent chemotherapy were independent prognostic factors on OS. Only seven patients (9%) experienced grade 3 toxicities that were gastrointestinal ulcer/bleeding (n = 4), anorexia (n = 1), leukopenia (n = 1), and neutropenia (n = 1). There was no grade 4 or 5 toxicity. Conclusions: C-ion RT for locally advanced PDAC was effective and well-tolerated.
Over-detection of colonic abnormalities on CTAP and a decrease with experience: A simulation of machine learning.
Authors: Chang John , Brooks Ryan , Gibson Zachary , Koo∗∗ Phillip , Dragovich Tomislav , Kundranda Madappa N.
Published: February 2020

68

Background: Artificial intelligence (AI) can potentially improve patient care by assisting physicians as demonstrated with the recent approvals for technologies that detect intracranial hemorrhage on CT exams of the head. AI also has potential for assisting early detection of colorectal cancer (CRC) on routine CT abdomen and pelvis (CTAP). We assessed the difference in detection of abnormal colonic findings between an expert reader (JC) and amateur readers (ARs). Methods: ARs consisting of two third year medical students (RB - AR1, ZG - AR2) studied 20 CTAP for tracing the colon and identifying pathology. Their search pattern and assessment of the colon was then evaluated by an expert radiologist (JC). They then spent two hours reviewing abnormalities in 10 scans with JC, who highlighted suspicious neoplastic findings such as colonic wall thickening, fat stranding, edema, masses, and abnormal lymph nodes. The ARs then individually read 203 CTAP scans to assess for these suspicious findings. The studies were from a single institution and were reported in a prior study in 2019 GI-ASCO. The findings of the ARs were then compared to those of the expert reader and the initial reader for each study. Data was analyzed using t-test with 2 tails. Results: The incidence of suspicious neoplastic findings was 87% and 81% for AR1 and AR2, respectively, compared to 18% in the initial reads and 33% for expert reader (p=0.01). Greatest discordance were 94% and 87% between AR1 and AR2 to the initial reads. Additionally, the incidence of suspicious findings between the first and last 20 cases (p=0.03 and 0.17) examined by ARs declined from 79 to 40% for AR1 and 69 to 55% for AR2. Conclusions: ARs are capable of detecting CRC features on CTAP from ED, but with higher false-positive (FP) rate than trained experts. The FP rate decreases with increasing experience. ARs learning course simulates AI which will likely yield high FP rate with initial training, but with improving FP with deep training, especially with larger volume of normal variants.
Survival and quality of life after isolated upper abdominal perfusion with chemofiltration (UAP-F) for stage III and IV pancreatic cancer.
Authors: Aigner Karl R , Gailhofer Sabine , Selak Emir , Aigner Kornelia
Published: February 2020

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Background: In order to increase response and survival rates of advanced pancreatic cancer at good quality of life, UAP-F was clinically tested. We report on feasibility, safety, overall survival and quality of life of 79 patients in stage III and 142 patients in stage IV submitted to UAP with subsequent chemofiltration for lowering of systemic drug exposure. Methods: This technique is achieved with stop-flow balloon catheters introduced via the femoral artery and vein. The arterial balloon is placed below the celiac axis and proceeded beneath the diaphragm after injection of a three-drug combination consisting of cisplatin (CDDP), adriamycin (ADM) and mitomycin (MMC). Because of tenfold increased cytotoxicity of ADM and MMC, the perfusion is performed under hypoxic condition. Perfusion time is 15 minutes followed by 30 – 45 minutes of chemofiltration. Results: Median survival was 12.1 months and 8.7 months in stage III and IV respectively. One-year survival was 49.4 % and 37 % for stage III and IV, and 3-years survival 21.7 % and 7.7 % for stage III and IV respectively. Cisplatin levels in the arterial circuit amounted to 60.000 ng/ml and 6.000 ng/ml in the venous line. Resolution of ascites was achieved within two therapies in 33/36 cases with UAP-F. Toxicity was generally mild, not exceeding WHO grade II and amounted to grade III or IV only in patients after prior severe systemic chemotherapy. Conclusions: Upper abdominal perfusion with chemofiltration is a safe technique for advanced cancers of the pancreas, increasing survival time and maintaining quality of life.
Phase Ib study of gemcitabine, nab-paclitaxel, and ficlatuzumab in patients with advanced pancreatic cancer.
Authors: Perez Kimberly , Weekes Colin D. , Cleary James M. , Abrams Thomas Adam , Blaszkowsky Lawrence Scott , Enzinger Peter C. , Giannakis Marios , Goyal Lipika , Meyerhardt Jeffrey A. , Rubinson Douglas Adam , Yurgelun Matthew B. , Stonely Danielle , Raghavan Srivatsan , Bakir Basil , Das Koushik , Pitarresi Jason , Aguirre Andrew , Needle Michael N. , Rustgi Anil , Wolpin Brian M.
Published: February 2020

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Background: Paired-related homeodomain transcription factor 1 (Prrx1) isoforms are involved in pancreatic development, pancreatitis, and carcinogenesis. Hepatocyte growth factor (HGF) is a transcriptional target of Prrx1b. Ficlatuzumab is a recombinant humanized HGF antibody, that neutralizes HGF/c-Met binding and HGF-induced c-Met phosphorylation. In preclinical pancreatic ductal adenocarcinoma (PDAC) models, inhibition of Prrx1b-HGF signaling using ficlatuzumab and gemcitabine reduced primary tumor volume and eliminated metastatic disease. Methods: Patients (pts) with previously-untreated metastatic PDAC enrolled in a phase Ib dose escalation study with 3+3 design and two dose cohorts of ficlatuzumab (10mg/kg and 20mg/kg) administered intravenously every other week with gemcitabine (G; 1000mg/m2) and nab-paclitaxel (A; 125mg/m2) given 3 weeks on and 1 week off. This was followed by an expansion phase at the maximally tolerated dose (MTD) of the combination. Results: 24 pts (sex, 12M:12F; median age, 69 years [range, 51-82 years]) were enrolled. No dose-limiting toxicities were identified in the phase 1b (N = 6 pts) and ficlatuzumab at 20mg/kg with GA was advanced to the expansion phase (N = 18 pts). By RECISTv1.1 in the full study population, 7 (29%) pts had partial response, 15 (63%) had stable disease, and 2 (8%) could not be evaluated. Median progression-free survival was 8 months (range, 3-16 months), 4 pts are still on study treatment. The primary toxicities attributed to ficlatuzumab included hypoalbuminemia (grade 3, 21%; any grade, 91%) and edema (grade 3, 8%; any grade, 91%). Nine (38%) of the 24 pts discontinued study treatment due to these toxicities prior to disease progression. Conclusions: The combination of ficlatuzumab with gemcitabine and nab-paclitaxel is associated with durable treatment responses but also significant hypoalbuminemia and edema that may impair treatment tolerability. Serial blood samples were collected for circulating HGF measurements, and mandatory pretreatment biopsies were collected for tumor c-MET pathway activation and 3D organoid culture drug sensitivity testing. Clinical trial information: NCT03316599.
The development of therapeutic cancer vaccine for pancreatic cancer.
Authors: Yamaue Hiroki , Miyazawa Motoki , Katsuda Masahiro , Kawai Manabu , Hirono Seiko , Okada Ken-Ichi , Kitahata Yuji , Ueno Masaki , Hayami Shinya
Published: February 2020

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Background: A previous phase II/III trial using a single cancer peptide vaccine derived from vascular endothelial growth factor receptor (VEGFR)2 for patients with advanced pancreatic cancer did not demonstrate the overall survival (OS) benefit (Yamaue et al. Cancer Sci 2015). However, for the next trial, we conducted a multicenter phase II study using multipeptide cocktail vaccine named OCV-C01 derived from a novel higher immunogenic antigen KIF20A, VEGFR1 and VEGFR2 combined with gemcitabine in postoperative adjuvant setting. Methods: A single-arm multicenter phase II study was performed on 30 patients with pancreatic ductal carcinoma who underwent pancreatectomy. At each 28-day treatment cycle, patients received weekly subcutaneous injection of OCV-C01 for 48 weeks, and gemcitabine was administered intravenously at 1,000 mg/m2 on days 1, 8, and 15 for 24 weeks. Patients were followed for 18 months. The primary endpoint was disease-free survival (DFS) and secondary endpoints included safety, OS and immunological assays on peptide-specific cytotoxic T lymphocyte (CTL) activity and KIF20A expression in resected pancreatic cancer. Results: The median DFS was 15.8 months (95% confidence interval (CI), 11.1-20.6), and the DFS rate at 18 months was 34.6% (95% CI, 18.3-51.6). The median OS was not reached and the OS rate at 18 months was 69.0% (95% CI, 48.8-82.5). The administration of OCV-C01 was well tolerated. In the per protocol set, there were significant differences in DFS between patients with and without KIF20A-specific CTL responses (p = 0.027), and between patients with and without KIF20A expression in resected pancreatic cancer tissues (p = 0.014). In addition, all four patients who underwent R0 resection with KIF20A expression had no recurrence of pancreatic cancer with KIF20A-specific CTL responses. Conclusions: OCV-C01 combined with gemcitabine was tolerable with a favorable median DFS of 15.8 months. In cancer vaccine treatment, positive expression of targeted antigen was essential, and postoperative adjuvant setting was more suitable than advanced state of cancer. Clinical trial information: UMIN000007991.
The role of immunotherapy on the survival of pancreatic cancer patients.
Authors: Amin Saber Ali , Baine Michael , Meza Jane L. , Lin Chi
Published: February 2020

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Background: Immunotherapy has revolutionized the treatment landscape of many malignancies, but its therapeutic role in pancreatic cancer (PC) remains unclear. The objective of this study is to investigate the impact of immunotherapy on the overall survival of PC patients stratified by definitive surgery of the pancreas using the National Cancer Database (NCDB). Methods: Patients with pancreatic adenocarcinoma were identified from NCDB. Cox proportional hazard models were employed to assess the impact of immunotherapy on survival after being stratified by surgery and adjusted for age of diagnosis, race, sex, place of living, income, education, treatment facility type, insurance status, year of diagnosis, and treatment types such as chemotherapy and radiation therapy. Results: Of 252,280 patients who were analyzed, 214,632 (85.08%) had definitive surgery, and 37,638 (14.92%) did not get definitive surgery of the pancreas. In the surgery group, 351 (0.93%) received immunotherapy and 37,287 (99.07%) did not while in the no surgery group, 838 (0.39%) received immunotherapy and 213,804 (99.61%) did not. In the multivariable analysis, patients who received immunotherapy had significantly improved OS both in the no surgery group (HR: 0.886, CI: 0.655-0.714; P < 0.0001) and in the surgery group (HR: 0.846, CI: 0.738-0.971; P < 0.0001) compared to patients who did not receive immunotherapy. Treatment with chemotherapy plus immunotherapy was associated with significantly improved OS (HR: 0.871, CI: 0.784-0.967; P < 0.009) compared to chemotherapy without immunotherapy in the no surgery group, while it was not significant in the surgery group. Chemoradiation plus immunotherapy was associated with significantly improved OS (HR: 0.787, CI: 0.684-0.906; P < 0.0009) in the no surgery group and (HR: 0.799, CI: 0.681-0.938) in the surgery group compared to chemoradiation alone. Conclusions: In this study, the addition of immunotherapy to chemoradiation therapy was associated with significantly improved OS in PC patients with or without definitive surgery. The study warrants further future clinical trials of immunotherapy in PC.
Role of para-aortic lymph node sampling in pancreatic cancer surgery.
Authors: Kazami Yusuke , Ito Hiromichi , Ono Yoshihiro , Sato Takafumi , Inoue Yosuke , Takahashi Yu
Published: February 2020

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Background: In the management of pancreatic cancer, para-aortic lymph node (PALN) metastasis is regarded as distant metastasis, and systemic treatment is recommended. However, imaging study is not perfect to detect all PALN metastasis and the management of intraoperatively discovered PALN has been controversial. We hypothesized that sampling of PALNs on exploration could allow us to avoid pancreatic resection for patients who would not benefit. In this study, we evaluated the incidence and the effect on the long-term outcomes for patients with potentially resectable pancreatic cancer. Methods: Three hundred and ninety-two patients who had PALNs sampled upon potentially resectable pancreatic cancer from 2005 through 2014 were included in the study. All patients were appropriately staged preoperatively with CT/MRI and those with suspected PALN metastasis were not considered as candidates for resection. The patients whose resections were aborted because of liver metastasis or peritoneal dissemination discovered on exploration, or those who died within 30-days after the operation were not included. Evaluated outcomes were incidence of PALN metastasis and their recurrence-free and overall survivals (RFS, OS). Results: The patients’ median age was 74 years, and 58.6% was man. 67.8% had tumors at pancreatic head. Preoperative chemotherapy was given only on 16 patients (3.2%). Among 392 patients with PALNs sampled, 53 (13.5%) patients had metastasis; Resection was completed on 40 patients and resection was aborted on the rest. Among patients who underwent pancreatic resection, median RFS and OS were 10 and 12 months for patients with PALN metastasis, compared to 17 and 26 months for those without PALN metastasis (p < 0.001 for RFS and p < 0.001 for OS). The 5-year-OS rates for patients with/without PALN metastasis were 5.9% and 25% (p < 0.001). Among 53 patients with PALN metastasis, OS were not different between the patients who underwent resection and those who did not (median 13 months vs 17 months, p = 0.06), and there were no recurrence-free survivors. Conclusions: PALN sampling and evaluation before committing to resection is useful to identify the patients who can unlikely benefit and to avoid unnecessary morbid operation.
Efficacy and safety of nab-paclitaxel plus S-1(nab-P/S-1) versus nab-paclitaxel plus gemcitabine (nab-P/Gem) for first-line chemotherapy in advanced pancreatic ductal adenocarcinoma (aPDAC): A randomized study.
Authors: Zong Yuan , Peng Zhi , Wang Xicheng , Shen Lin , Zhou Jun
Published: February 2020

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Background: Nab-P/Gem significantly improved survival compared with gem in patients (pts) with metastatic PDAC, but the ORR was limited to 23% with increased myelosuppression. Two phase II trials demonstrated high ORR of 50.0-53.1% with nab-P/S-1 and showed less hematologic toxicity. Methods: A randomized (1:1) phase II trial was conducted. Eligibility required treatment-naïve pts with unresectable PDAC. Pts received nab-P 125mg/m2on day 1 + S-1 80-120mg orally per day on day 1-7 every 2 weeks or nab-P 125mg/m2+ Gem 1000mg/m2 on days 1,8 every 3 weeks. With an increase of ORR from 25% to 50%, 100 pts were required for 90% power at a two-sided significance level of 0.05. We enrolled 40 pts for a pilot study. Primary endpoints were ORR and 6-month PFS rate. Secondary endpoints were ORR of primary lesion, DCR, PFS, OS and safety. Results: 40 pts were enrolled between 06/2018 and 06/2019, including locally advanced (27.5%) and metastatic (72.5%) PDACs. 42.5% were male and the median age was 61 (range, 36-75) years old. The median duration of treatment was 2.3 months in nab-P/S-1 (n = 20) and 2.7 months in nab-P/Gem (n = 20). In the intention-to-treat (ITT) population, the ORR and DCR were 35.0% vs 25.0% ( P= 0.49) and 70.0% vs 70.0%, respectively.The ORR of primary lesion was 30.0% vs 25.0% ( P= 0.72). In the evaluable pts (nab-P/S-1 n = 18, nab-P/Gem n = 18), the ORR, DCR and the ORR of primary lesion were 38.9% vs 27.8%, 77.8% vs 77.8% and 35.3% vs 29.4%, respectively.With the median follow-up of 5.0 (range 0.3-11.4) months, the median PFS and 6-month PFS rate was 6.3 vs 5.7 months and 56.1% vs 36.2%( P= 0.61) for nab-P/S-1 and nab-P/Gem, respectively. The median OS have not reached. Grade 3/4 toxicities occurred in 30.0% nab-P/S-1 and 30.0% nab-P/Gem: leukopenia/neutropenia(15.0% vs 25.0%), febrile neutropenia (0 vs 5.0%), rash (0 vs 5.0%) and diarrhea (10.0% vs 0). Conclusions: Compared with nab-P/Gem, nab-P/S-1 had higher ORR, ORR of primary lesion and longer PFS without significant difference. Nab-P/S-1 developed a trend towards less hematologic toxicity. Follow up for survival is ongoing. Clinical trial information: 03636308.