bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association of mutant allele frequency of TP53 with response of chemotherapy in advanced gastric cancer patients.
Authors: Zhang Shu 
Published: January 2019

42 Background: The tumor suppressor gene TP53 is one of the most commonly altered genes in advanced gastric cancer (AGC). However, the predictive role of mutant allele frequency (AF) of TP53 on response of chemotherapy in AGC patients remains unclear. This study aims to explore the predictive value of mutant allele frequency of TP53 on efficacy of chemotherapy in AGC. Methods: We obtained a new biopsy using gastroscope and collected blood samples at baseline and at time of 3 cycles of chemotherapy (2 weeks each cycle) in 8 patients with AGC, and the circulating tumor DNA (ctDNA) and tumor tissue DNA were analyzed using next generation sequencing (NGS). The efficacy was evaluated at time of 3 cycles of chemotherapy by CT imaging according to the RECIST’s standard. Results: We selected 8 patients with advanced gastric adenocarcinoma confirmed pathologically, including 5 female, 3 male. Their Median age is 53 (32-78) years old. The sequencing depths of tissue samples and blood samples were greater than 1000x and 10000x, respectively. Of 8 patients, except for one patient with no mutation of TP53, 7 AGC patients had the mutations in the different sites of TP53 gene. The results showed that 5 patients had partial response (PR), and 2 patients revealed stable disease (SD) after chemotherapy. Five patients with PR showed more than 10% of mutant AF of TP53, but two patients with SD had less than 3% of the mutant AF. Of 5 AGC patients with PR, two patients showed that the mutant AF of TP53 had become from 77.0%, 20.20% to negative in the blood samples, three patients exhibited the decrease of mutant AF of TP53 from 36.99%, 21.61% and 10.04% to 15.77%, 0.40% and 0.69%, respectively. In two patients with SD, one patient revealed that the mutant AF of TP53 had decreased from 2.20% to negative, another one from 1.91% to 1.11%, respectively. Conclusions: Our results suggested that the decrease of mutant allele frequency of TP53 in blood sample can predict response to chemotherapy in patients with advanced gastric cancer. The AGC patients with more than 10% of mutant AF of TP53 maybe have a good outcome for chemotherapy but needs to be further explored.
Alpha fetoprotein (AFP) response and efficacy outcomes in the phase III CELESTIAL trial of cabozantinib (C) versus placebo (P) in advanced hepatocellular carcinoma (HCC).
Authors: Kelley Robin Kate , Rimassa Lorenza , Ryoo Baek-Yeol , Park Joong-Won , Blanc Jean-Frédéric , Chan Stephen Lam , Dadduzio Vincenzo , Yau Thomas Cheung , Sen Suvajit , Markby David W. , Kaldate Rajesh , El-Khoueiry Anthony B. , Cheng Ann-Lii , Meyer Tim , Abou-Alfa Ghassan K. 
Published: January 2019

423 Background: AFP response, defined as a decrease in serum levels of the tumor marker AFP after therapy, may be associated with improved survival of patients (pts) with HCC treated with locoregional or systemic therapy, and high baseline AFP levels may be associated with poor prognosis. In the phase III CELESTIAL trial (NCT01908426), C, an inhibitor of MET, VEGFR, and AXL, significantly improved overall survival (OS) and progression-free survival (PFS) versus P in pts with previously treated advanced HCC. Here we evaluate clinical outcomes with C in CELESTIAL based on AFP response or progression on treatment. Methods: 707 pts were randomized 2:1 to receive C (60 mg daily) or P. Eligible patients had a pathologic diagnosis of HCC, Child-Pugh score A, and ECOG PS ≤ 1. Pts received prior sorafenib and ≤ 2 lines of prior systemic therapy for HCC. Serum AFP levels were measured centrally at baseline and every 8 weeks thereafter. Outcomes were evaluated for pts with baseline AFP ≥ 20 ng/mL based on AFP response ( ≥ 20% decrease from baseline) or progression ( ≥ 20% increase from baseline) at Week 8. This definition of AFP response has been used in previous studies but requires further validation in large prospective studies. Results: Overall, 331 pts (70%) in the C arm and 160 (68%) in the P arm had baseline AFP ≥ 20 ng/mL; among these pts, 236 (71%) and 111 (69%), respectively, were evaluable for AFP response at week 8. Among evaluable pts, 117 pts (50%) in the C arm vs 14 (13%) in the P arm had an AFP response, and 72 (31%) vs 75 (68%) had AFP progression. Median OS with C was 16.1 mo for pts with an AFP response versus 9.1 mo for pts without a response (HR 0.61, 95% CI 0.45-0.84), and median PFS with C was 7.3 mo versus 4.0 mo (HR 0.55, 95% CI 0.41-0.74). For pts with AFP progression, median OS with C was 8.1 mo, and median PFS with C was 3.6 mo. Hazard ratios for OS and PFS with C also favored AFP responders over non-responders when analyzed using best response through week 24. Conclusions: The AFP response rate was higher with C versus P, and AFP response was associated with longer OS and PFS with C for pts with previously treated advanced HCC. On-treatment AFP changes warrant further evaluation as a biomarker of response. Clinical trial information: NCT01908426.
Carcinoids of the ampulla: Long-term follow-up after endoscopic resection.
Authors: Baison George Nyasha , Sahar Nadav , Bonds Morgan M , Rekman Janelle F , Rocha Flavio G. , Irani Shayan 
Published: January 2019

430 Background: Neuroendocrine tumors (NET) or carcinoids of the ampulla are exceedingly rare in comparison to duodenal NET. Surgical management is widely accepted as the treatment of choice, but for patients that refuse surgery or are poor operative candidates, endoscopic resection may be option. We present a consecutive case series at a tertiary care center describing our experience with endoscopic resection of ampullary NET. Methods: This is a restrospective review with a long-term follow-up of patients with ampullary NET that were endoscopically resected. Outcomes were analyzed based on the histopathologic classification system proposed by the World Health Organization in 2000. Results: Twelve patients (9 male, 3 female), ranging in age from 41 to 86 (mean 59) underwent endoscopic ampullectomy for ampullary NET, with a mean follow-up time of 5 years. Patients had refused surgery or were poor surgical candidates. All, but one incidentally found case, were symptomatic on presentation, with gastrointestinal bleeding being the main symptom. No patients had a hormonal syndrome. The mean size of the lesions was 21 mm (6 mm to 35 cm). Six (50%) patients had a well-differentiated, benign lesion, 6 (50%) patients had a well-differentiated NET with unknown malignant potential (gangliocytic paragangliomas). Eight (67%) were completely excised during the initial endoscopy with 4 requiring re-excision. Only 2 patients developed recurrence, after 2.5 and 10 years and this necessitated a pancreaticoduodenectomy. Five patients had complications (2 for bleeding and 3 for post-ERCP pancreatitis), with zero deaths. Conclusions: Unlike duodenal carcinoids, ampullary NET are rare. Pancreaticoduodenectomy can be offered to fit patients except for gangliocytic paragangliomas that do not require an aggressive operation. However, for those that refuse surgery or are poor candidates, endoscopic ampullectomy can be an option with acceptable short and long-term outcomes.
Treatment of hepatocellular carcinoma (HCC) after sorafenib (S) over the last 10 years.
Authors: Fung Andrea S. , Lee-Ying Richard M. , Meyers Daniel E. , Sim Hao-Wen , Knox Jennifer J. , Zaborska Valeriya O. , Davies Janine Marie , Ko Yoo-Joung , Batuyong Eugene , Cheung Winson Y. , Samawi Haider , Tam Vincent C. 
Published: January 2019

438 Background: Until recently there were no standard treatments for HCC patients after S. This study characterizes subsequent treatments (STx) received by HCC patients over the past 10 years and assesses their impact on survival. Methods: HCC patients treated with S between 01/2008 – 06/2017 in British Columbia, Alberta, and two cancer centers in Toronto, Ontario, Canada (Princess Margaret and Sunnybrook Cancer Centre) were included. Clinical, pathologic, laboratory, treatment, and outcome data were collected. The Kaplan-Meier method was used to assess overall survival (OS) based on STx, and stratified according to a better prognostic group (BPG), defined as ECOG 0-1 and CP-A, and worse prognostic group (WPG), defined as ECOG≥2 or CP-B/C. Results: A total of 730 patients were identified. 177 (24.2%) received STx (table). Patients who received STx had longer median OS (mOS) than those who had no further treatment (12.1 vs. 3.3 months; p < 0.001). For patients treated with localized, systemic, or palliative radiation treatment, mOS was 16.8, 10.5 and 8.6 months, respectively (p < 0.001). After S, there were 206 (30.7%) patients in the BPG and 464 (69.3%) in the WPG. BPG patients were more likely to receive STx compared to WPG patients (60.5% vs. 39.5%, p < 0.001). BPG patients who received STx had better mOS than those who did not (15.9 vs. 7.0 months; p < 0.001). WPG patients also had better mOS if they received STx compared to those who did not (6.0 vs. 2.6 months; p < 0.001). Conclusions: Only a small proportion of HCC patients received subsequent treatment after sorafenib. This is likely due to poor performance status, liver dysfunction, or lack of treatment options. Patients who received subsequent treatment had improved mOS, regardless of whether they were in the better or worse prognostic group. [Table: see text]
Undertreatment of noncurative pancreatic adenocarcinoma?: A population-based analysis of patterns of care.
Authors: Mavros Michail , Davis Laura , Mahar Alyson L. , Beyfuss Kaitlyn , Earle Craig , Liu Ying , Coburn Natalie , Hallet Julie I. 
Published: January 2019

439 Background: Noncurative pancreatic adenocarcinoma (PA) portends a guarded prognosis. Advancements in systemic therapy have improved this outlook. It is unknown whether patients get access to these therapies. We sought to define patterns of access to care and therapy for noncurative PA. Methods: We conducted a population-based analysis of nonresected PA over 2005-2016 by linking administrative healthcare datasets. Primary outcome was nonreceipt of cancer-directed therapy (radiation/chemotherapy; NRCDT). The first contact and overall consultations with specialized care (surgery, medical, or radiation oncology) were examined. Multivariate models examined factors associated with NRCDT. Results: Of 10,881 patients surviving a mean of 3.3 months (IQR: 1.2-8.5), 62% had NRCDT. More of patients of older age (65% of 71-80 years old, 89% of ≥81 years old), high comorbidity burden (68%), and lower socioeconomic status (69%), had NRCDT. Distance from residence to nearest cancer centre did not differ based on NRCDT. 35% of all patients did not see medical oncology, including 56% of NRCDT patients; 17% had no consultation with specialists. First contact with specialized care was surgery for 55% of all patients, and 50% with NRCDT. Most patients saw palliative care (81%) at median 27 days (IQR: 9-75) after diagnosis. Older age (OR 0.42 [0.37-0.48], and OR 0.14 [0.12-0.16] for 71-80 and ≥81 years old respectively), lowest income quintile (OR 0.62 [0.54-0.71]) and rurality (OR 0.63 [0.56-0.71]) were independently associated with lower odds of seeing medical oncology. First contact with oncology was independently associated with higher odds of receiving therapy (OR 1.48 [1.34-1.62]), compared to surgery. Conclusions: The majority of patients with noncurative PA did not receive cancer-directed therapy. Of those, more than half did not see medical oncology. While some patients may not be eligible to therapy, we identified disparities in receipt of cancer-directed therapy that indicate potential gaps in assessment for therapy and undertreatment, especially for vulnerable populations. This information is important to optimize access to and delivery of evidence-based care, and improve PA outcomes.
Dosing modifications to increase tolerability of gemcitabine and nab-paclitaxel in treatment of pancreatic cancer in the elderly.
Authors: Martin Jasmine L , Sidhu Simran , Benhayoun Nabil , Dedonno Michael , Brenner Warren S. 
Published: January 2019

441 Background: Gemcitabine and nab-paclitaxel has been reported to prolong survival in patients with metastatic pancreatic cancer. This drug combination was studied in such patients in the MPACT trial with an average age of enrolled patients being 63. Pancreatic cancer, however, is a disease of the aging with a median age at diagnosis of 70. Reductions in dosing by 20% or more in one or both components and has been shown to improve the tolerability of this regimen, thereby increasing treatment exposure. Our study aims to examine the efficacy and tolerability of this drug combination in an elderly population and how this is affected by schedule and dosing modifications. Methods: A retrospective chart review was performed of 83 patients over the age of 70 with a median age of 79 who received this drug combination as first-line treatment for pancreatic adenocarcinoma at a single institution. Overall survival and progression-free survival were assessed as well as schedule modification, dose reduction, and rates of adverse events. Results: For patients with metastatic or non-metastatic disease, the mean overall survival and progression-free survival were found to be 10.57 months and 6.63 months, respectively. When only patients with metastatic disease are analyzed, these values were found to be 9.26 months and 6.05 months, respectively, which are similar to those observed in the MPACT trial. The most common adverse events of grade 3 or greater were fatigue in 34.9% of patients and hematologic adverse events including neutropenia in 27.7% and leukopenia in 25.3% of patients. Dose reductions were commonly used to mitigate adverse events. Reductions in either one or both drugs by at least 20% occurred in 84.3% of patients. Conclusions: Gemcitabine and nab-paclitaxel in treatment of pancreatic cancer is well tolerated in an elderly population with similar rates of adverse effects when compared with previous studies, though this population experienced a significantly higher rate of fatigue. Dose reductions were used frequently in this population to improve tolerability, which may have contributed to the observed increase in overall survival in this population.
Combined radiotherapy and transarterial chemoembolization as a first-line treatment for hepatocellular carcinoma with macroscopic vascular invasion.
Authors: Yoon Sang MIN , Joo Ji Hyeon , Jung Jinhong , Kim Yeon Joo , Park Jin-hong , Kim Jong Hoon 
Published: January 2019

452 Background: To evaluate the long-term clinical outcome of respiratory-gatedconformal radiotherapy in combination withtransarterial chemoembolization (TACE)asafirst-line treatment foradvanced hepatocellular carcinoma (HCC) with macroscopic vascular invasion (MVI). Methods: This was a retrospective analysis of patientswho were diagnosed with HCC showing MVI who received TACE plus radiotherapy as their initial treatment between 2010 and 2015. Inclusion criteria were Child-Pugh A or B hepatic function and Eastern Cooperative Oncology Group performance score 0–2. None of the patients had a previous history of radiotherapy to the liver or extrahepatic metastasis. Results: A total of 467 patients were included in the study. Patients were between 34 and 87 years of age, and 89.3% were male. The median maximum tumor diameter was 9.8 cm and 297 patients (63.6%) had Child-Pugh A hepatic function. Two hundred and eighty (60%) patients had multiple tumors; 45% of tumors showed bilobar involvement. Unilateral portal vein invasion was observed in 206 (44.1%) patients and main/bilateral portal veinor multiple vascular invasion were observed in 261 (55.9%) patients. The median overall survival was 12.5 months, with one- and two-year survival rates of 52% and 28%, respectively. Larger tumor size, multiple tumors, infiltrative tumor type, Child-Pugh class B, and alpha-fetoprotein ≥ 200 ng/ml were independent predictors of overall survival. Grade ≥ 3 hepatic and gastrointestinal toxicities were observed in 3 (0.6%) and 5 (1.1%) patients, respectively. Conclusions: Radiotherapy combined with TACE as an initial treatment was a safe and effective modality for advanced HCC patients with MVIand could be considered as first-line therapy in patients with liver-confined HCC showing MVI.
A randomized phase III trial of S-1/oxaliplatin (SOX) versus UFT/leucovorin as adjuvant chemotherapy for high-risk stage III colon cancer: The ACTS-CC 02 trial.
Authors: Takahashi Takao , Sunami Eiji , Kusumoto Tetsuya , Ota Mitsuyoshi , Sakamoto Yoshiyuki , Tomita Naohiro , Maeda Atsuyuki , Tejima Jin , Okabe Michio , Tanaka Chihiro , Yamauchi Junichiro , Itabashi Michio , Kotake Kenjiro , Takahashi Keiichi , Baba Hideo , Boku Narikazu , Aiba Keisuke , Ishiguro Megumi , Morita Satoshi , Sugihara Kenichi ,   ACTS-CC 02 Study Group
Published: January 2019

484 Background: The ACTS-CC 02 trial was designed to verify the superiority of postoperative adjuvant chemotherapy with S-1/oxaliplatin (SOX) over UFT/leucovorin (LV), one of the standard oral fluoropyrimidine regimens in Japan, in terms of disease-free survival (DFS) in patients (pts) with high-risk stage III colon cancer (any T, N2, or positive nodes around the origin of the feeding arteries). The results of the safety analysis have been reported previously (Clin Colorectal Cancer, 2018). We now present the 3-year DFS results as the primary endpoint. Methods: Pts who underwent curative resection for pathologically confirmed high-risk stage III colon cancer were randomly assigned to receive either UFT/LV (300–600 mg/day of UFT according to body surface area [BSA] and 75 mg/day of LV on days 1-28, every 35 days, 5 courses) or SOX (100 mg/m2 of oxaliplatin on day 1 and 80–120 mg/day of S-1 according to BSA on days 1-14, every 21 days, 8 courses). The primary endpoint was DFS. Results: From April 2010 through October 2014, a total of 966 pts were enrolled at 260 institutions. The full analysis set, excluding pts who withdrew informed consent before protocol treatment, comprised 478 and 477 pts in the UFT/LV group and SOX group, respectively. The median age was 65.0 years. The ECOG PS was 0 in 94.0%, and the disease stage was IIIA/IIIB/IIIC in 1.3%/50.2%/48.6%. The 3-year DFS rate was 60.6% in the UFT/LV group and 62.7% in the SOX group (HR: 0.90; 95% CI: 0.74-1.09; p = 0.28); the superiority of SOX was not demonstrated. In stage IIIB, the 3-year DFS rate was 69.3% and 68.5% in the UFT/LV group and SOX group, respectively (HR: 1.01; 95% CI: 0.74-1.37; p = 0.95). In Stage IIIC, the 3-year DFS rate was 50.6% and 55.8% in the UFT/LV group and SOX group, respectively (HR: 0.82, 95% CI: 0.63-1.06; p = 0.12). Notably, in the N2b subgroup, the 3-year DFS rate was 46.0% and 54.7% in the UFT/LV group and SOX group, respectively (HR: 0.76, 95% CI: 0.55-1.05; p = 0.10). Conclusions: SOX was not shown to be superior to UFT/LV in pts with high-risk stage III colon cancer. However, the oxaliplatin-based regimen was suggested to be more effective in advanced disease, such as stage IIIC and N2b. Clinical trial information: JapicCTI-101073.
Recent trends in age at diagnosis of colon cancer in the United States, 2004-2015, a National Cancer Database study.
Authors: Goodgame Boone Wilder , Virostko Jack , Capasso Anna , Yankeelov Thomas 
Published: January 2019

490 Background: The incidence of colorectal cancer (CRC) in adults younger than age 50 has been increasing in the US since 1970. The US Preventive Services Task Force recommends screening for CRC beginning at age 50, while the American Cancer Society recently revised its guidelines to advise screening at age 45. We analyzed the National Cancer Database (NCDB) from 2004 through 2015 to determine whether the proportion of patients diagnosed younger than 50 has changed during this time. Methods: This was a retrospective study of NCDB data, which includes more than 70 percent of newly diagnosed cancer cases in the US. We examined the proportion of patients diagnosed prior to age 50 as our primary endpoint. We used the Cochran–Armitage test for trend to assess changes in the proportion of cases diagnosed at age < 50 years old as a function of year of diagnosis. Results: We identified 152,749 patients diagnosed under age 50 and 1,033,014 patients diagnosed at age 50 or greater. Over the study period, the proportion of the total number of patients diagnosed with colorectal cancer under age 50 increased (14.3% in 2015 vs. 11.5% in 2004, p < 0.0001). Younger adults with CRC presented with more advanced disease, with 49.9% stage III or IV disease, as compared to 40.0% in those diagnosed over age 50. Both men and women had a rising proportion of cases diagnosed younger than 50 (p < 0.0001) over time. In men, only non-Hispanic whites had an increase in diagnosis at ages less than 50 (p < 0.0001), while in women, all racial and ethnic subgroups had an increase in younger diagnoses over time (p < 0.01). All income quartiles (p < 0.001) demonstrated a proportional increase in younger adults over time, with the highest income quartile having the highest proportion of younger cases. The proportion of younger-onset CRC rose in urban areas (p < 0.001), but did not rise in rural areas. Conclusions: The proportion of persons diagnosed with CRC under age 50 in the US has continued to increase over the past decade. Younger adults presented with more advanced disease, suggesting that screening could improve outcomes.
Novel radiomics signature predicts lymph node metastasis in T1 colorectal carcinoma.
Authors: Ma Yanlei , Zhang Sheng , Li Xinxiang , Niu Tianye 
Published: January 2019

506 Background: This study evaluates the predictive performance of radiomic features in metastasis of T1 colorectal carcinoma (CRC) to lymph nodes. Methods: A total of 10 200 CRC patients from our clinical cancer center included in this analysis. 225 eligible cases diagnosed with T1 CRC were included and divided into two groups: computed tomography (CT) image group (n = 82) and magnetic resonance image (MRI) group (n = 143) based on the preoperative image data available. A total of 548 radiomic features were extracted from each case and analyzed, and then a panel of radiomic features associated with lymph node metastases (LNM) were selected using Mann-Whitney U test. Combining these selected radiomic features and clinical data, the predictive performance for LNM was calculated using receiver operating characteristic (ROC) curves. Results: The prediction accuracy for LNM of T1 CRC could be improved to 0.88 by area under the receiver operating characteristic curve (AUC) through integration of one radiomic feature and three clinical indicators in CT group. In the group of contrast enhanced T1-weighted MRI (T1w-MRI), combination of two radiomic features and three clinical parameters present an AUC value of 0.85. In the group of T2-weighted MRI (T2w-MRI), combination of four radiomic features and five clinical characteristics identified T1 tumors with LNM with an AUC value of 0.87. Conclusions: The current study present a good predictive performance of combination of radiomic features with clinic characteristic in identifying T1 CRC with LNM, which may provide an important opportunity for us to make clinical treatment decision-making for T1 CRC patients.