bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of adjuvant therapy in patients with a microscopically positive margin after resection for gastroesophageal cancer.
Authors: Ma Lucy Xiaolu , Espin-Garcia Osvaldo , Lim Charles Henry , Sun Peiran , Jiang Di Maria , Sim Hao-Wen , Natori Akina , Chan Bryan Anthony , Yokom Daniel , Moignard Stephanie , Suzuki Chihiro , Chen Eric Xueyu , Liu Geoffrey , Swallow Carol Jane , Darling Gail Elizabeth , Wong Rebecca , Hafezi-Bakhtiari Sara , Conner James , Elimova Elena , Jang Raymond Woo-Jun
Published: January 2019

164

Background: A microscopically positive (R1) resection margin following resection for gastroesophageal (GE) cancer has been documented to be a poor prognostic factor. The optimal strategy and impact of different modalities of adjuvant treatment for an R1 resection margin remain unclear. Methods: A retrospective analysis was performed for patients (pts) with GE cancer treated at the Princess Margaret Cancer Centre from 2006-2016. Electronic medical records of all pts with an R1 resection margin were reviewed. Kaplan-Meier and Cox proportional hazards methods were used to analyze recurrence free survival (RFS) and overall survival (OS) with stage and neoadjuvant treatment as covariates in the multivariate analysis. Results: We identified 78 GE cancer pts with an R1 resection. 11% had neoadjuvant chemotherapy, 14% chemoradiation (CRT), 75% surgery alone. 28% had involvement of the proximal margin, 13% distal, 56% radial, 3% had multiple positive margins. By the American Joint Committee on Cancer 7th edition classification, 88% had a pT3-4 tumour, 66% pN2-3 nodal involvement, 64% grade 3, 68% with lymphovascular invasion. 3% were pathological stage I, 21% stage II and 74% stage III. Adjuvant therapy was given in 46% of R1 pts (24% CRT, 18% chemotherapy alone, 3% radiation alone, 1% reoperation). Median RFS for all pts was 12.6 months (95% CI 10.3-17.2). Site of first recurrence was 71% distant, 16% locoregional, 13% mixed. Median OS was 29.3 months (95% CI 22.9-50) for all pts. The 5 year survival rate was 23% (95% CI 12%-43%). There was no significant difference in RFS (log-rank test p= 0.63, adjusted p= 0.14) or OS (log-rank test p= 0.68, adjusted p= 0.65) regardless of adjuvant therapy. Conclusions: Most pts with positive margins after resection for GE cancer had advanced pathologic stage and prognosis was poor. Our study did not find improved RFS or OS with adjuvant treatment and only one pt had reresection. The main failure pattern was distant recurrence, suggesting that pts being considered for adjuvant RT should be carefully selected. Further studies are required to determine factors to select pts with good prognosis despite a positive margin, or those who may benefit from adjuvant treatment.
The association of 5FU-based chemotherapy with pathological response or survival compared to carbo/taxol with locally advanced resectable esophageal cancer.
Authors: Al-Jumayli Mohammed , Abbasi Saqib , Kasi Anup , Saeed Anwaar
Published: January 2019

165

Background: Neoadjuvant chemoradiation followed by esophagectomy is the standard of care in advanced EC. While 5FU based chemoradiation has been a common regimen in the past, its utilization has declined in recent years as the CROSS trial study regimen of carboplatin/paclitaxel has become widely adopted. A prospective evaluation of the CROSS regimen compared to the 5FU based regimen was never performed. The aim of this study is to report our institutional experience with these two chemotherapy regimens. To the best of our knowledge, this is the largest retrospective study comparing the two types of chemotherapy regimens. Methods: We performed an IRB-approved retrospective review of a prospectively maintained institutional cancer registry. EC patients who completed trimodality therapy with either carboplatin/paclitaxel or 5FU/platinum were identified and divided into groups based on their chemotherapy regimens. Multivariable logistic regression was used to analyze pathologic complete response (pCR) rates, while the Kaplan–Meier and Cox proportional hazards models were utilized to evaluate DFS and OS. Analytical models were adjusted for age, stage, radiation dose, histology sub-type, and time interval from completion of neoadjuvant therapy to surgery. Results: 224 patients treated between January of 2007 and July of 2017 were identified . Of this group, 139(62%) had received Carbo/Taxol, while 85 (37%) had received 5FU/platinum. There was no increase in the odds of pCR with 5FU based chemo compared to CROSS regimen (OR = 2.68, P = 0.671). Furthermore, the OS and DFS of 159 patients(80 5FU/platinum, 77 carbo/taxol) with median follow up of ~ 5 yrs were not statistically different with HR 1.08 (0.6-1.7) and P value 0.71. Conclusions: Neoadjuvant chemoradiation with 5FU/platinum in resectable EC is not associated with higher rates of pCR, DFS and OS compared to the CROSS regimen of carbo/taxol. Those findings will need to be validated in a larger cohort.
Impact of preoperative treatment with chemoradiotherapy or chemotherapy in patients with locally advanced or irresecable gastric cancer (LAGC).
Authors: Diaz Romero C , Calderillo Ruiz G , Herrera Marytere , Ruiz Garcia E , Lopez Basave H , Leon Takahashi A
Published: January 2019

167

Background: The only curative treatment for gastric cancer remains surgery neoadjuvant chemoradiotherapy (NACRT) has shown decrease of staging and improve survival. La NACRT has been studied in esophagus cancer and Gastroesophagic Junction cancer but this trials did not include advanced gastric disease. The aim of our study was to investigate the role of Chemoradiotherapy (CTR) and chemotherapy (CT) in the treatment of LAGC. Methods: We retrospectively reviewed the medical records of 108 patients who were treated between December 2010 and January 2015, with preoperatory CRT or chemotherapy preoperatory (CT). Evaluating parameters of resectability, pathological response complete, prognostic with a 3-year follow-up. Results: 108 patients were analyzed, 61 man and 47 women, with median age 55 years, 83 (76.8%) with diffuse, 25 (23.2%) intestinal histology, however 83 patients (76.8%) had component of signet ring cells. Of the 108 patients, 41 (38%) received chemotherapy and 67 (62%) received CRT preoperative. R0 radical surgery was possible in 41 patients of which 24.3% (10/41) were in the group of CT and 46% (31/67) CRT group. Radiological progression was documented in 8 (19.5%) patients with CT and 11 (16.4%) with CRT. 7 patients were considered inoperable and 17 unresectable at the end of the preoperative treatment. The carcinomatosis was documented during the surgery in 11 and 12 patients in the CT or CRT group respectively. 10 patients developed complications gastrointestinal and hematologic to the treatment with CT and 23 patients with CRT, which 4 patients in CRT needed reoperation post-surgery. Any patient in the chemotherapy group reached complete pathologic response while of the CRT group achieved 5 complete pathological responses. Medium-3 years follow-up survival rate was 11% in the group treated with CT and 23% with CRT. Conclusions: Our revision showed a high rate of pathologic response and survival in patients with LAGC that received CRT preoperative followed by gastrectomy. On the other hand R0 resection has been reported to be a predictive factor for survival in this study were found more patients with resectable tumor after CRT preoperative.
Feasibility study of diet counseling (DC) with oral nutritional supplements (ONS) for advanced esophageal and gastric cancer during chemotherapy (CT) or chemoradiotherapy (CRT): First report of ONS compliance from a prospective randomized controlled clinical study (DiCON study).
Authors: Izawa Yukiko , Ichimura Takashi , Chin Keisho , Shinozaki Eiji , Takahari Daisuke , Suenaga Mitsukuni , Ogura Mariko , Wakatsuki Takeru , Osumi Hiroki , Nakayama Izuma , Mine Shinji , Hiki Naoki , Ishizuka Naoki , Yamaguchi Kensei
Published: January 2019

17

Background: Most advanced esophageal and gastric cancer patients(pts) experience fatigue, anorexia, and may arise malnutrition and sarcopenia, for which effective treatment has not been established. Nutritional support especially protein supplementations may prevent loss of body mass related with malnutrition and sarcopenia. We therefore, conducted a prospective randomized study to explore compliance and the best available ONS intake for pts undergoing CT or CRT. Methods: Eligibility criteria included: chemo-naïve advanced gastric cancer or esophageal cancer; performance status (PS) of 0–1; pts who can eat more than as 50% as usual; age over 20 years. Pts were randomly allocated into four groups within each strata, i.e. esophageal or gastric cancer, Group A: Diet counseling (DC) only, Group B-1: DC and ONS 1 pack/day, Group B-2: DC and ONS 2 packs/day, and Group B-3: DC and ONS 3 packs/day. We use jelly type ONS which is easy to intake and include rich branched-chain amino acid. We assessed ONS compliance, the change of nutritional index (body weight, albumin, pre-albumin, and muscle mass), diet record (daily), and toxicity before CT or CRT and 14 days after administration of CT. Results: Among forty pts (11 in A, 11 in B-1,8 in B-2,10 in B-3) were enrolled from August 2017 to August 2018, median age was 64 years (range 46-81), median BMI was 20.6 (range 15-29), and 28 gastric cancer, 12 esophageal cancer. Median intake was 12 packs/2w (range 0-14), 15 packs/2w (3-28), 12 packs/2w (2-28), in B-1, B-2, and B-3 respectively. Mean compliance of ONS was 72.7%, 50.0% and 33.1%, in B-1, B-2, and B-3 respectively. There was a significant linear trend across the 3 groups (P = 0.0104). B-1 was significantly better than B-3 (P = 0.0270). There were no pts in group B-3 who could intake ONS for 14 consecutive days. Over 80% of pts in B-1 group were able to intake for 14 consecutive days. Conclusions: We found ONS 3 packs/day was clearly denied because of compliance. Choice of 1 or 2 packs/day should be determined by taking into account the total calories of foods. Clinical trial information: 000026705.
Impact of clostridium difficile infection on gastrointestinal malignancies.
Authors: Perimbeti Stuthi , Shrivastav Rishi , Pati Prateeth , Ward Kristine Marie , Styler Michael , Jain Maneesh Rajiv , Nandi Neilanjan
Published: January 2019

170

Background: According to the Centers for Disease Control and Prevention, there were half a million documented cases with 83,000 re-infections and 29,000 deaths due to Clostridium Difficile Infection(CDI) in the year 2011. The influence of CDI on outcomes in gastrointestinal(GI) malignancies is not well described, although the incidence is known to be higher in this subgroup of patients. Methods: National Inpatient Sample 1999-2014 was analyzed to identify adult admissions (>18 years of age) using ICD-9-CM codes with a primary diagnosis of esophageal(EC), Gastric(GC), Colorectal(CRC), Small intestinal(SIC), Hepatobiliary(HCC) and Pancreatic(PC) cancers. ICD-9 code 00845 was used to stratify these for the presence of CDI. We performed Chi-Square test to determine the in-hospital mortality percentage, and Cox Proportional Hazard model to control for confounders and determine the Hazard Ratio(HR) of death within 30 days of admission during hospitalization in patients with and without CDI. Results: See table. Conclusions: Despite controlling for potential confounders, patients with GI cancers and CDI are at an increased risk of death compared to those without CDI. Taking the more detrimental effects of CDI in this subgroup of patients into consideration, healthcare professionals should strive to avoid the inordinate use of antibiotics and strictly maintain current guidelines designed to prevent spread. It may be prudent to treat these patients as severe CDI, even if current criteria are not met. More scientific research is warranted in analyzing the specific outcomes of CDI in GI cancer patients and if more aggressive therapy for CDI is warranted, considering the limitations of this study. [Table: see text]
Randomized, open-label, perioperative phase II study evaluating nivolumab alone versus nivolumab plus ipilimumab in patients with resectable HCC.
Authors: Kaseb Ahmed Omar , Carmagnani Pestana Roberto , Vence Luis M. , Blando Jorge M. , Singh Shalini , Ikoma Naruhiko , Vauthey Jean-Nicolas , Allison James Patrick , Sharma Padmanee
Published: January 2019

185

Background: In HCC, surgical resection is associated with high recurrence rate, and no effective neoadjuvant or adjuvant therapies currently exist. On the basis of previous reports on the efficacy and safety of anti–PD-1 and anti–CTLA-4 antibodies against HCC, we initiated a randomized pilot trial of perioperative immunotherapy for resectable HCC. Methods: This is a randomized, phase II trial of nivolumab (Arm A) or nivolumab + ipilimumab (Arm B) as peri-operative treatment for patients (pt) with HCC who are eligible for surgical resection. Pt are given nivolumab 240 mg every 2 weeks (wk) for a total of 6 wk. Pt in Arm B are treated concurrently with ipilimumab 1 mg/kg every 6 wk. Surgical resection occurs within 4 wkafter last cycle of therapy. Pt continue adjuvant immunotherapy for up to 2 years after resection. Primary objective is the safety and tolerability of nivolumab +/- ipilimumab. Secondary objectives include overall response rate, complete response rate and time to progression. Exploratory objectives include evaluating the pre- and post-treatment immunological changes in tumor tissues and peripheral blood. Results: 9 pt were enrolled at the time of first interim analysis, and 8 pt were evaluable (5 in Arm A, 3 in Arm B). Pt were 60-69 yo, and males (78%). 5 pt were HCV-positive and 1 had chronic hepatitis B infection. 8 pt proceeded with resection as planned; surgery was aborted for 1 pt due to frozen abdomen from previous surgery. Pathologic complete response (pCR) was observed in 3/8 pt – 2 in Arm A and 1 Arm B (37.5% pCR). 2 pt in Arm B and 1 in Arm A experienced grade 3 or higher toxicity which did not affect their resectability. No grade 4 or higher toxicity were observed. Immune analysis of the first case with a pCR in Arm B demonstrated that clinical response correlated with an increase in CD8+ T cell infiltration, notably an increase in two effector T cell clusters. Conclusions: We report a pCR rate of 37.5% in the first interim analysis of a phase II pilot trial of perioperative immunotherapy for resectable HCC. Treatment was deemed safe and surgical resection was not delayed. The study is ongoing and results may contribute to a paradigm shift in the perioperative treatment of HCC. Clinical trial information: NCT03222076.
Distribution of insulin growth factor-1 (IGF-1) binding proteins in hepatocellular carcinoma with and without cirrhosis.
Authors: Abdelhakeem Ahmed , Kaseb Ahmed Omar , Hatia Rikita , Abdel-Wahab Reham , Amin Hesham M. , Hassan Manal
Published: January 2019

193

Background: Circulating insulin-like growth factor-1 (IGF-1) significantly declines in patients (pts) with cirrhosis and hepatocellular carcinoma (HCC), reflecting damaged hepatocytes. The bioavailability of IGF-1 is controlled by insulin-like growth factor binding proteins (IGFBPs), which bind IGF-1. IGFBPs transcription is cell specific, and are secreted mainly by the liver. Variations in circulating IGFBPs in HCC pts, especially those with non-cirrhotic HCC, has not been elucidated. We investigated the expression of these proteins in HCC with and without cirrhosis. Methods: Under Institutional Review Board approval, we measured plasma levels of seven IGFBPs in 489 cirrhotic HCC pts, 274 non-cirrhotic HCC pts, 75 pts with cirrhosis without HCC, and 200 healthy controls. Also, we assessed variations in IGFBPs plasma level between early and advanced stage HCC in the presence and absence of cirrhosis. Levels of circulating biomarkers were summarized by descriptive statistics, and both Chi-square and ANOVA tests were used to compare levels between groups. Results: IGFBPs levels varied significantly between groups (Table). Moreover, IGFBP-3 was lower in HCC pts than in healthy controls ( P ≤ 0.001), and IGFBP-1, -2, -4, and -7 were higher in HCC without cirrhosis than in healthy controls ( P = 0.001 for all). Additionally, in non-cirrhotic HCC pts, a similar pattern was observed in advanced Stage HCC compared with early stage HCC. Conclusions: Levels of circulating IGFBPs may be associated with risk of non-cirrhotic HCC and could be used as markers for underlying liver damage. [Table: see text]
Development of a nomogram to predict overall survival in patients presenting with gastrointestinal neuroendocrine carcinoma (WHO G3).
Authors: Lin Zhenyu , Wang Haihong , Zhang Dejun , Yu Dandan , Zhang Tao
Published: January 2019

197

Background: To evaluate the prognostic factors in patients with gastrointestinal neuroendocrine carcinoma (WHO G3) (GI-NEC) and develop a nomogram to predict 1-year overall survival (OS). Methods: We performed a retrospective analysis of 122 patients with GI-NEC. Nomogram for 1-year OS was created as visualizations of Cox proportional hazards regression models and internally validated by use of bootstrap and cross-validation. We assessed nomogram model performance by examining overall accuracy (Brier score), calibration (calibration plot), and discrimination (Harrell C index). Results: The median survival was 9 months in 122 patients, and 51 (41.8%) patients died in the development cohort. A 1-year OS was chosen because 82% of the patients who died from disease did so within 1 year. Multivariable analysis identified prognostic factors including performance status, stage, Ki-67 index and LDH, all of which were included in the final model. In the development cohort, the Harrell C index for overall survival was 0·887 (95% CI 0·810-0·964), and calibration curves showed adequate calibration (judged by eye) of the observed and predicted probabilities. Conclusions: Prognostic factors were used to develop nomograms for 1-year OS for GI-NEC. The nomogram can be offered to clinicians to improve their abilities to assess patient prognosis, strengthen the prognosis-based decision making, enhance patient stratification, and inform patients in the clinic.
Hepatocellular carcinoma (HCC) survival by etiology: A SEER-Medicare database analysis.
Authors: Brar Gagandeep , McNeel Tim , McGlynn Katherine , Graubard Barry , Floudas Charalampos S. , Morelli M. Pia , Xie Changqing , Greten Tim F. , Altekruse Sean
Published: January 2019

201

Background: HCC is the 6thmost common occurring cancer worldwide and the 4th leading cause of cancer mortality, with a survival of 6-9 months. While survival varies by stage at diagnosis and treatment, the effect of HCC etiology on survival is unclear. We analyzed the SEER-Medicare database to evaluate whether HCC survival varied by etiology, after adjusting for stage, treatment, and survival. Methods: A total of 11,522 SEER-Medicare HCC cases (ICD-O-3 codes C22 for topography, 8170-8175 for morphology) met criteria for the Cox proportional hazard analyses to assess survival differences among the risk factors for hepatitis C virus (HCV) infection, hepatitis B virus (HBV) infection, alcohol disorders, and metabolic disorders. These analyses were adjusted for covariates for gender, age at diagnosis, race, ethnicity, tumor size and extent of disease, a modified Charlson Index of comorbidities, and treatments that included resection, transplantation, ablation, arterial directed therapy and radiotherapy. Cases with multiple and unknown etiologies were included in analyses, however genetic disorders and primary biliary cirrhosis were excluded due to their rarity. Results: HBV associated cases had the highest proportion of single nodules (40% vs 33% overall), localized stage disease (57% vs 49%), treatment (40% vs 27%), and greatest frequency of resection (18.6% vs 9%). Non-Hispanic Asians/Pacific Islanders accounted for 69% of HBV infection-related HCC cases but only 16% of all cases. HBV associated cases had better survival than did HCC cases with other etiologies. Specifically, after adjusting for demographic and clinical attributes, compared to cases with HBV infection, the risk of death was highest for alcohol-related HCC (HR=1.69; 95%CI:1.42-2.01) followed by multiple etiologies (HR = 1.40; 95% CI: 1.20-1.64), metabolic disorders (HR = 1.32; 95% CI: 1.13-1.55), HCV infection (HR = 1.30; 95% CI: 1.10-1.53), and HCC of unknown etiology (HR = 1.22; 95% CI: 1.04-1.43). Conclusions: Persons with HBV associated HCC had better survival than persons with HCC of other etiologies. Efforts to identify people with any etiologic risk factors for HCC, treat their conditions, and screen for HCC may improve overall survival.
Characteristics and epidemiology of gastric cancer in Korea: Disparity in sex and age according to histologic classification.
Authors: Kim Dongwoo , Lee Sang Woo , Hwang Su Hyun , Kim Seung Young , Hyun Jong Jin , Jung Sung Woo , Koo Ja Seol
Published: January 2019

21

Background: Gastric cancer (GC) is one of the most common cancers worldwide. The overall incidence of gastric cancer is higher in males, but signet ring cell carcinoma (SRC) is more common in younger females. However, the sex disparity according to the histological classification of GC in Korea has not studied much. The aim of this study is to analyze the difference of clinical manifestation between sex groups and to assess sex disparity to gastric cancer. Methods: We retrospectively analyzed 1488 patients (459 females (30.8%) and 2017 males (69.0%)) who diagnosed with gastric cancer at Korea University Ansan Hospital from 2009 to 2017. The patients were divided into three groups according to Lauren’s classification: Intestinal type GC (IGC), diffuse type GC (DGC), mixed type. The difference of clinicopathologic characteristics between these groups and sex groups were compared. Results: The age-group-specific annual incidence rates for intestinal and diffuse type GC were analyzed. The incidence of IGC increased from 40s in males. In females, the incidence of DGC was higher in young age and the proportion of IGC was increased rapidly after age 60 in females. Most of IGC appeared after age 60. (19.3% in below 60 vs. 80.7% in above 60 in females, 35.1% vs. 64.9% in males, p < 0.001) IGC seemed to appear 10-20 years earlier in male than female. Female patients were associated with poorly differentiated adenocarcinoma, SRC and DGC. Diffuse and mixed type GC was more frequent with younger, female patients and associated with advanced GC and TNM stage. Kaplan-Meier analysis revealed that the patients with IGC had a higher cumulative survival rate than those with DGC (5-year survival rate 88.2% vs. 80.5%, p < 0.001). Conclusions: Female patients with IGC were older than male patient and appeared about 10-20 years later. But this difference did not observed in DGC. Therefore, unlike DGC, sex hormones such as estrogen may act in development of IGC. This is supported by an increase of IGC in females after menopause. Further studies on role of estrogen in the development of gastric cancer are needed.
Prevalence of pancreaticobiliary cancer in Irish families with BRCA1 and BRCA2 mutations.
Authors: Power Robert , Leavy Cristin , Nolan C. , White Niamh , Clarke R. M. , Gallagher David James , Lowery Maeve Aine
Published: January 2019

210

Background: Germline mutations in BRCA1 and BRCA2 genes are associated with pancreatic ductal adenocarcinoma (PDAC), and more recently associated with increased risk of biliary tract cancers (BTC). This study assessed the prevalence, age and gender distribution of PDAC/BTC in BRCA1/2 positive families; compared to those of the Irish population. Methods: A review of all families referred to a national genetics clinic from 09/11/1997-01/06/2018 was performed following institutional ethics board approval. Demographics including age, sex and BRCA mutation status was collected in each case of PDAC/BTC. The BOADICEA algorithm was used to estimate the probability that an untested relative of a known BRCA1/2 mutation carrier with PDAC was a carrier. Results: 3252 distinct family pedigrees were reviewed, of which 1193 contained a proband who underwent testing for BRCA1/2 based on Manchester score ≥ 15. Among 128 BRCA2 positive families, 27 (21%) contained a 1st/2nd or 3rd degree relative with PDAC, of 116 BRCA1 positive families, 11 (9%) contained a 1st/ 2nd or 3rd degree relative with PDAC (male: female (m:f) = 1:0.9). Of these 38 families, 25 pts with PDAC had ≥ 50% likelihood of being a mutation carrier by BODICEA analysis. This cohort had a median age at diagnosis of 55 (33-75), with a mean (55) significantly lower than that of 8364 unselected patients with PDAC identified through the National Cancer Registry Ireland (71, p < 0.0001). Six BRCA2 positive (5%) and 2 BRCA1 positive pedigrees (2%) contained an individual with BTC; median age at diagnosis was 65 (33-99, m:f = 1:7). Additional pedigrees with Lynch Syndrome (n = 3), FAP (n = 1) and ATM (n = 2) and PDAC were identified. Conclusions: PDAC and BTC are prevalent in Irish families with a BRCA1/2 mutation and are associated with early onset malignancy. This consolidates evidence of PDAC and BTC as BRCA- associated cancers in the Irish population and supports current guidelines recommending universal germline testing for PDAC patients. [Table: see text]
Preoperative evaluation with computed tomography (CT) of the resectability of mesenteric lymph node metastases in small intestine neuroendocrine neoplasms (si-NENs): New criteria for clinicians and surgeons.
Authors: Funicelli Luigi , Bertani Emilio , Zugni Fabio , Bellomi Massimo , Fazio Nicola
Published: January 2019

212

Background: The 2016 European Neuroendocrine Tumor Society consensus guidelines update recommends resection of the primary tumor and all mesenteric lymph-nodes for all patients with si-NENs, both with curative and palliative purposes. Current resectability criteria are based on the degree of involvement of the superior mesenteric artery (SMA) by the metastatic lymph nodes. The aim of this work was to test these criteria for the evaluation of our patients; we included as additional criteria the degree of involvement of the superior mesenteric vein (SMV) and peritoneum, two features not covered by current literature. Methods: We retrospectively reviewed the pre-operative CT-scans of all patients with si-NENs operated at IEO (European Institute of Oncology) between 2008 and April 2018. A first analysis classified tumors as “resectable” or “unresectable” according to SMA involvement. A second analysis classified tumors as resectable or unresectable according to SMA involvement, SMV involvement (infiltration of the peripheral or proximal portion) and peritoneal involvement (presence or absence of fibrosis and retraction of the mesentery). We finally reviewed all surgery reports assessing radicality and completeness of the operation. Results: Abdominal CT-scan were available for analysis in 42 out of 47 operated patients. According to the first analysis, all three tumors classified as unresectable underwent incomplete resection, whereas out of the 39 tumors classified as resectable, six received an incomplete resection and 33 were completely resected. According to the second analysis, the nine tumors classified as unresectable underwent an incomplete resection, whereas 33 tumors classified as resectable were completely resected. Conclusions: Our retrospective analysis confirmed that SMA involvement may be useful to evaluate the resectability of the primary tumor and mesenteric lymph nodes. Furthermore, it suggested that the additional evaluation of the SMV and peritoneum involvement can allow to identify further cases of tumors for which complete resection is not possible.
Prognostic significance of nutritional and inflammatory markers in patients with unresectable pancreatic ductal adenocarcinoma treated with chemotherapy.
Authors: Kobiyama Ryosuke , Yoshioka Isaku , Ando Takayuki , Kajiura Shinya , Shibuya Kazuto , Sekine Shinichi , Hirano Katsuhisa , Baba Hayato , Arai Mie , Sukegawa Kenta , Watanabe Toru , Hashimoto Isaya , Hojo Shozo , Okumura Tomoyuki , Nagata Takuya , Murotani Kenta , Yasuda Ichiro , Fujii Tsutomu
Published: January 2019

219

Background: Recently, several nutritional and inflammatory markers have been reported to be involved in cancer progression. The aim of this study is to evaluate whether nutritional and inflammatory biomarkers such as the modified Glasgow prognostic score (mGPS), the neutrophil‐to-lymphocyte ratio (NLR), the platelet‐to-lymphocyte ratio, the systemic-immune-inflammation index (SIII), controlling nutritional status (CONUT) score, prognostic nutritional index, and the lymphocyte‐to-monocyte ratio (LMR) could predict the prognosis in patients with unresectable pancreatic ductal adenocarcinoma (UR-PDAC) who underwent chemotherapy as first-line therapy, using disease-specific survival as the primary outcome. Methods: All UR-PDAC patients were retrospectively evaluated between January 2011 and May 2017 at Toyama University Hospital. Baseline clinicopathological characteristics and pre-treatment laboratory values such as absolute neutrophil, lymphocyte and platelet counts, C-reactive protein, albumin and CA19-9 levels, were collected. Results: A total of 184 patients were diagnosed as UR-PDAC. Among them, 151 patients who underwent chemotherapy were enrolled in this study. There were significant relationships between survival and elevated mGPS, elevated NLR, elevated SIII, decreased LMR, decreased serum cholinesterase level, and low CONUT score (p < 0.001, p < 0.001, p = 0.001, p < 0.001, p = 0.026 and p < 0.001, respectively, by log-rank test). The median survival time of patients with metastatic lesions was significantly shorter than that of patients with unresectable locally advanced PDAC (9.0 vs 15.5 months, respectively; p = 0.033). There was no significant difference in survival in pre-treatment CA19-9 level and tumor location. Multivariate analysis using Cox regression model revealed that NLR and CONUT score were independent prognostic factors. Conclusions: Pre-treatment NLR and CONUT score may predict clinical outcome in patients with UR-PDAC undergoing chemotherapy as first-line therapy.
IGF-Child-Pugh score as a predictor of treatment outcome in Child-Pugh A, advanced hepatocellular carcinoma patients undergoing sorafenib therapy.
Authors: Abugabal Yehia I. , Hassan Manal , Xiao Lianchun , Morris Jeffrey , Carmagnani Pestana Roberto , Abdel-Wahab Reham , Hatia Rikita , Chang Ping , Girard Lauren , Rashid Asif , Bhawana George , Raghav Kanwal Pratap Singh , Abdelhakeem Ahmed , Wolff Robert A. , Amin Hesham M. , Kaseb Ahmed Omar
Published: January 2019

223

Background: Sorafenib is the first systemic therapy approved for advanced HCC treatment; with no accurate tool available to help predict survival and treatment outcome and to guide therapy decisions. Our novel blood-based IGF-Child-Pugh (CP) score comprises levels of IGF-1, bilirubin, INR, and albumin. IGF-CP score significantly improved the prediction of HCC survival in our recently published studies. The current prospective study aimed to compare the overall survival (OS) and progression free survival (PFS) of 101 patients with CP-A HCC treated with sorafenib whose score is reclassified as IGF-A (AA) to that of patients whose score is reclassified as IGF-B/C (AB/AC). Methods: Between 2014 and 2018, after the approval of the institutional review boards and signing written informed consent, a total of 101 patients with HCC, CP-A were prospectively enrolled and started on sorafenib and followed until progression or death. Results: Sixty-three patients were evaluable. Patients who were reclassified by the IGF-CTP scoring system were better stratified by their new risk groups. Forty-two of patients were classified as IGF-CTP-A and had median PFS of 4.87 months (95% CI=2.3 to 6.84), and median OS of 15.43 (95% CI = 12.04 to 31.18 months), whereas 21 patients were reclassified as intermediate risk (IGF-CTP-B) and had significantly shorter OS of 7.6 months (p-value<0.0001) and shorter PFS of 2.86 months (p-value=0.0021). Conclusions: The results of this study confirms our biologically driven hypothesis that: among HCC patients with “old CP-A” class treated with sorafenib, some will be reclassified as “new CP-B/C” will have poorer prognosis in terms of shorter OS and PFS. Thus, our study provides an objective non-invasive strategy to better predict the outcome in HCC patients undergoing systemic therapy. Future validation of our IGF score may lead to adopting it as a stratification tool in trials to predict HCC outcome and guide therapy decision in routine practice. [Table: see text]
Designing clinical trials in 3L+ pancreatic cancer.
Authors: Manax Victoria G. , Chatikhine Valery , Kirven Saundra , Taylor Ben R
Published: January 2019

226

Background: An increasing percentage of pancreatic cancer (PC) patients are looking for 3L+ options. As patient outcomes are improving with advances in treatment for PC, more patients need 3L+ treatments. Few trials focus on this patient segment as evaluation of drug effects can be complicated by comorbidity rates and disease-related SAEs. Having exhausted SOC chemotherapy backbones, patients increasingly search for novel therapies and clinical trial options. This assessment was to evaluate 3L+ PC trials for 1) sufficient patient interest, 2) a clinically evaluable patient population, and 3) guidelines/restrictions that could improve clinical assessment. Methods: Initiated as a retrospective evaluation of consenting patients screened for a prospective 2L+ pancreatic cancer Phase II trial with SM-88. A comparison of recurrent PC trials was performed by Novella to assess industry wide enrollment characteristics. Results: 32% of patients searching for clinical trials YTD 2018 in PanCAN’s database were looking for 3L+ treatments, up from 25% in 2016. In the sample trial, rate of consents (n=72) increased hyperbolically, reaching ~1/pt/day by end of analysis (24 sites). Inc/exc criteria were broadly standard for sponsor-initiated trials, however ECOG PS 2 were eligible. 38% screen failed, with hepatic labs (esp Alb & ALP) as most common reason. Industry analysis indicated expected 0.35 p/s/m for refractory PC trials and 20% screen fail. 93% (37/40) of SAEs were unrelated to study drug, including 11 G4 or G5 prior to receiving drug. Preliminary safety and efficacy results for the trial are reported elsewhere. Conclusions: Rapid enrollment from 3L+ patients demonstrated significant interest among this patient segment. The screen failure rate was within reasonable expectations, implying a majority of the patients were within standard inc/exc criteria. The high level of unrelated SAEs during the consent period and initial enrollment period indicate this may not be a suitable population to properly assess drug safety. Subgroup statistical analyses may be more relevant than ITT medians since several comorbidities, such as biliary obstruction, have elsewhere been demonstrated to have a dramatic impact on OS. Clinical trial information: NCT03512756.
VTE among pancreatic cancer and its possible risk factors among metastatic pancreatic cancer (mPC): Experience at Fox Chase Cancer Center.
Authors: Pandey Ramesh Kumar , Sorice Kristen , Gou Jiangtao , Lynch Shannon M. , Blumenreich Aryeh , Cheema Khadija , Nagappan Lavanya , Dotan Efrat , Vijayvergia Namrata
Published: January 2019

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Background: The incidence of VTE is relatively high among mPC pts, upto 57%. It is associated with higher health care burden and mortality. We evaluated the mPC pts treated at a single academic center from 2010-16 for prevalence of VTE, its impact on survival and possible risk factors. Methods: Medical charts of mPC pts treated at a single academic center were analyzed retrospectively for VTE diagnosis, overall survival and potential risk factors for VTE development. The factors considered were: age, sex, stage, body mass index, smoking status, surgery, performance status (PS), Charlson comorbidity index (CCI) and treatment. Logistic regression was used to identify the factors correlating with VTE and Cox Proportional Hazard model was used to evaluate overall survival (OS) differences between those with VTE (Gp A) and those without VTE (Gp B). Results: Out of the 439 mPC pts (52% males, 86% with PS0-1, 63% with stage IV at diagnosis), 127 (29%) were in Gp A and 312 (71%) in Gp B. The groups were well balanced with respect to all factors except age (median age 67 Gp A; 65 in Gp B, p = 0.04). 2.3 % of pts in Gp A and 4.8 % pts in Gp B were on anticoagulation for reason other than VTE treatment. Within Gp A, 55% developed VTE after diagnosis of metastasis. A clear separation of the survival curves noted beyond the median OS (9 m, P = 0.02), favoring GpB. Statistically significant factors associated with risk of VTE included advanced stage at diagnosis (P = 0.004) and worse PS (P = 0.005). Treatment regimen used and CCI didn’t correlate with the risk of development of VTE. Conclusions: The incidence rate of VTE in our patients is lower than published literature, yet the diagnosis of VTE was associated with worse OS. Most cases occurred after the diagnosis of metastatic disease. The higher use of anticoagulants for other medical causes may be contributing to a lower incidence of VTE in mPC. These findings need prospective Validation.
Factors associated with biopsy diagnosis of hepatocellular carcinoma.
Authors: Rho Young soo , Acoba Jared David
Published: January 2019

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Background: Hepatocellular carcinoma (HCC) is one of the few cancers that can be diagnosed based on imaging findings. Although not always mandatory for diagnosis, biopsy (Bx) can confirm HCC and its histologic subtype. We have demonstrated that Bx is associated with worse survival compared to imaging diagnosis in a multivariate analysis. In turn, factors associated with undergoing a Bx diagnosis were examined. Methods: We obtained demographic, diagnostic, and treatment data of 171,013 patients diagnosed with HCC between 2004–2015 from the National Cancer Database. Binary logistic regression examined factors associated with Bx. Variables analyzed included race, sex, age, comorbidity, facility type, insurance, tumor size, presence of metastatic disease, alpha fetoprotein, total bilirubin, year of diagnosis and administration of therapy. Analysis was performed using SPSS v25. Results: We included 160,517 patients for the final analysis. The median age was 62 (18–90), 73.9% were male and 74.1% were white. 11.5% of tumors were 2 cm or smaller and 13.7% of HCC were metastatic. 78,485 (47.7%) underwent Bx. In a multivariate model, black patients (OR 1.093; 95% CI: 1.061-1.126), older patients (OR 1.579; 95% CI 1.537–1.622), larger tumor size (OR 3.208; 95% CI: 3.085–3.335), private (OR 1.129; 95% CI 1.094-1.164) or Medicare insurance (OR 1.056; 95% CI 1.021–1.093), and metastasis at time of diagnosis (OR 1.318; 95% CI 1.275–1.361) were associated with Bx diagnosis. Factors associated with an imaging diagnosis were female (OR 0.964; 95% CI 0.941–0.987), Asian/Pacific Islanders (OR 0.686; 95% CI 0.657–0.717), more comorbidities (OR 0.578; 95% CI 0.559–0.597), treatment at an academic center (OR 0.447; 95% CI 0.436–0.458), hyperbilirubinemia (OR 0.807; 95% CI 0.784-0.831) or elevated AFP (OR 0.571; 95% CI 0.549-0.594). Over the examined study period 2004-2015, imaging diagnosis was increasingly used. Conclusions: Although imaging alone can be adequate to diagnose many cases of HCC, nearly half of the cohort underwent a Bx. Even though diagnosis by imaging was more frequently used in recent years, there were still racial and institutional differences in pattern of care.
Dose intensity of nab-paclitaxel and gemcitabine chemotherapy in metastatic pancreatic cancer.
Authors: Lim Alexander , Kim Dae Won , Kim Kunhwa , Kim Richard D. , Bottiglieri Salvatore Michael
Published: January 2019

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Background: Combination chemotherapy with nab-paclitaxel/gemcitabine is a standard of care option in metastatic pancreatic cancer management with increasing use due to an improvement in median overall survival of 1.8 months compared to gemcitabine alone. It is also used in practice in the second and third-line settings for patients that have progressed on fluorouracil based regimens. As the utility of this combination chemotherapy has grown, dose intensity (DI) in relation to survival outcome is an important measure for real world application. Methods: Fifty-six patients that were 18 years or older with metastatic pancreatic cancer treated with nab-paclitaxel/gemcitabine as first-line therapy from January 1, 2013 to December 31, 2014 at Moffitt Cancer Center were identified through medical records. The subjects were retrospectively reviewed, and demographic, treatment outcomes (survival and progression), and DI were collected. Overall survival was calculated with Kaplan Meier survival curves. Multi-Cox regression models estimated multivariable-adjusted hazard ratio with 95% confidence intervals. Results: There was no significant relationship between receiving a DI > 85% regimen in relation to independent variables of age > 65, sex, primary site, and known distant metastasis; however DI > 85% was significant for patients that received additional chemotherapy following nab-paclitaxel/gemcitabine (p = 0.044). The DI > 85% group compared to the < 85% group had a hazard ratio (HR) for all-cause mortality of 0.285 (0.106-0.764, p = 0.013). Six and 12-month survival were higher in the DI > 85% group (p = 0.009, p = 0.02 respectively). Conclusions: DI > 85% for nab-paclitaxel/gemcitabine compared to DI < 85% may have a lower all-cause mortality and higher 6 and 12-month survival.
Imaging findings of patients undergoing SBRT for HCC after prior TACE.
Authors: Maleeva Aneliya , Thomas Tarita , Yacoub Joseph H
Published: January 2019

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Background: Our purpose is to assess the treatment response using follow up MRI or CT in lesions treated with stereotactic body radiation therapy (SBRT) after transarterial chemoembolization (TACE). Methods: Twenty-six patients treated with liver SBRT at our institution in the period between 2015 and 2017. Of these we included patients who had lesions diagnosed as HCC (LR-5) or probable HCC (LR-4), and who had prior TACE with a residual/recurrent enhancing component on the pre SBRT images with adequate post SBRT imaging. One radiologist (5 year experience) evaluated all pre and post SBRT imaging and measured the lesion size and the size of the largest enhancing component. Lesion decrease or increased in size was assessed based on the mRECIST criteria. Explant pathology results were collected for patients who received transplant. Necrosis > 90% on explant was considered full response to treatment. AFP (alpha-fetoprotien) values before and after SBRT were collected. Results: Eight patients with 9 lesions meet our inclusion criteria, 3 of which were LR-5 and 6 LR-4 prior to the TACE. At 3 month, 2 lesions had no residual enhancing component, 2 lesions decreased in size, 2 lesions increased in size, 3 lesions remain unchanged. After maximum available follow-up (ranging from 3 to 8 months), 3 lesions had no residual enhancing component, 2 decreased, 2 lesions increased in size, 2 lesions remain unchanged. Of the 3 lesions that were definitive HCC (LR-5): 1 lesion decreased in size, 2 lesions increased in size. 4 of 8 patients (4 lesions) underwent transplant, 3 of them showed only 50% necrosis on explant. 1 of 3 lesions showed no change in size by imaging, the other 2 lesions had no residual enhancing component. Only 1 lesion had full response on the transplant. This lesion was unchanged on 3 and 6 months follow up. The AFP was not helpful since the majority of the patient had low pre-treatment AFP. Conclusions: Patient with viable disease on imaging after TACE subsequently treated with SBRT demonstrated variable behavior on imaging. Close to half demonstrated resolution of the enhancing component, however, in the few that had explant follow up there was no correlation between imaging findings and pathology.
Investigation of aberrant DNA methylation in association with cisplatin-resistant hepatoblastoma.
Authors: Fujiyoshi Sunao , Honda Shohei , Hiyama Eiso , Taketomi Akinobu
Published: January 2019

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Background: Cisplatin (CDDP) is a key-drug of mainstream treatment for hepatoblastoma (HB), but 22.3% of HB patients have resistance to CDDP, and their prognoses are poor. We investigated methylation status of HB patients and identified CDDP resistant candidate genes in HB. Methods: First, we performed a genome-wide methylation array analysis of 11 resected HB tumors. These cases included six cases of RECIST (Response Evaluation Criteria In Solid Tumors) CR or PR (S group) and five cases of SD or PD (R group). We analyzed methylation status of these patients, comparing with clinical course, and selected significant differentially methylated genes. Next, We made CDDP-resistant HepG2 cells by repeated CDDP treatments for a year, then compared expression levels between the CDDP-resistant cells and original cells, using cDNA microarray analysis. We selected CDDP resistant candidate genes from these data. Results: In methylation array analysis data, unsupervised hierarchical clustering analysis showed that methylation profiles were separable into 2 groups in accord with clinical S group and R group. In principal component analysis, the S group also showed a different methylation pattern to the R group. We compared survival rates using Kaplan-Meier method, and results showed that the R group had poorer prognosis significantly. The R group showed 336 hypermethylated genes and 106 hypomethylated genes around the transcriptional start site compared with S group significantly. And in cDNA microarray analysis, 1271 genes were downregulated and 1571 genes were upregulated significantly in CDDP-resistant cells. From among these genes, we selected 15 suppressor and 8 promoter candidate genes that could be related to CDDP-resistance. Conclusions: We identified methylation status associated with CDDP resistance and poor prognosis, and 23 candidates genes in HB. Further refining might lead us to find out the pathogenesis of chemoresistance or new target of therapies and biomarkers in HB.