bluuebunny/crossref_metadata_2025 huggingface dataset:
C-reactive protein at 4 days after surgery as an early predictor of serious infectious complications following esophageal cancer surgery.
Authors: Kano Kazuki , Ogata Takashi , Maezawa Yukio , Segami Kenki , Nakajima Tetsushi , Ikeda Kousuke , Sato Tsutomu , Cho Haruhiko , Yoshikawa Takaki
Published: February 2017

10

Background: Serious infectious complications (SICs), frequently observed morbidities, have been reported to be related not only with short-term mortality but also with poor long-term survival in various types of malignancies including esophageal cancer. SICs usually develop 7 to 10 days after esophagectomy and early diagnosis is believed to be difficult because systemic response by SICs is considered to be covered by surgical invasion. The aim of this study was to investigate whether serum C-reactive protein (CRP) on postoperative day (POD) 4 can be predictor of SICs after esophageal cancer surgery. Methods: The present study retrospectively examined 110 consecutive patients undergoing open thoracic esophagectomy after neoadjuvant chemotherapy for thoracic esophageal cancer between January 2011 and June 2015. All patients received perioperative care of enhanced recovery after surgery program with steroid therapy. SICs were defined as morbidity of grade III or more according to the Clavien-Dindo classification. Diagnostic accuracy was determined by measuring the area under the receiver operating characteristic curve (AUC). Clinical and laboratory parameters including CRP, all available before or within POD 4, were analyzed with univariate and multivariate logistic regression model to identify SICs. Results: Median age was 68 years. SICs were observed in 20 patients (18.2%). CRP on POD 4 had superior diagnostic accuracy for PICs (AUC 0.759; 95% confidence interval [CI], 0.652-0.866). Cut-off value for CRP was determined as 4.0 mg/dl which yielded a sensitivity of 70.0%, a specificity of 74.4% and a negative predictive value of 91.8% for the detection of SICs. Multivariate analysis identified CRP ≥ 4.0 mg/dl on POD 4 (odds ratio of 8.399 with 95% CI, 2.646–26.666) and three-field lymph node dissection (odds ratio of 4.658 with 95% CI, 1.306–16.619) as predictive factors for SICs after esophagectomy. Conclusions: CRP on POD 4 was an early indicator for serious infectious complications after esophageal cancer surgery, which could encourage imaging study to detect the focus or early intervention by antibiotics.
Subset of patients with unfavorable T1N2-3M0 gastric cancer for whom surgery alone is the standard treatment.
Authors: Maezawa Yukio , Sato Tsutomu , Aoyama Toru , Kano Kazuki , Segami Kenki , Nakajima Tetsushi , Ikeda Kousuke , Hayashi Tsutomu , Yamada Takanobu , Kunisaki Chikara , Oshima Takashi , Rino Yasushi , Masuda Munetaka , Ogata Takashi , Cho Haruhiko , Yoshikawa Takaki
Published: February 2017

105

Background: ACTS-GC trial demonstrated that S-1 is effective as adjuvant chemotherapy for Japanese patients who have undergone curative D2 gastrectomy for gastric cancer and were diagnosed with pathological stage II disease. However, stages T1N2M0 and T1N3M0, which are classified as part of Stage II, were excluded from the ACTS-GC trial. The aim of the present study was to identify the unfavorable subset of patients with T1N2M0 and T1N3M0 gastric cancer for whom surgery alone is the standard treatment. Methods: The present study examined 59 patients who were diagnosed with T1N2M0 or T1N3M0 gastric cancer at Kanagawa Cancer Center and Yokohama City University Hospital between January 2000 and June 2010. Univariate and multivariate analyses were performed to identify risk factors for overall survival using a Cox proportional hazards model. Results: When overall survival was compared by the log-rank test, a significant difference was observed with regard to macroscopic tumor diameter. A macroscopic tumor diameter greater than 30mm was regarded as a critical point of classification considering the survival. Mulitivariate Cox’s proportional hazard analyses demonstrated that macroscopic tumor diameter was the only significant independent prognosticator. The five-year survival was 60.0% in patients with a macroscopic tumor diameter < 30mm, and 84.6% in those with a macroscopic tumor diameter > 30mm (P = 0.027). Conclusions: Among T1N2M0 and T1N3M0 gastric cancer patients for whom surgery alone is the standard treatment, having a small T1N2-3 tumor of less than 30 mm in diameter was the sole risk factor for gastric cancer survival. These tumors might be another target for adjuvant chemotherapy.
Survival benefit of additional surgery after non-curative endoscopic resection in patients with early gastric cancer.
Authors: Ryu Keun Won , Eom Bang Wool , Kim Young-Il , Kim Kwang Hee , Nam Byung-Ho , Yoon Hong Man , Cho Soo-Jeong , Lee Jong Yeul , Kim Chan Gyoo , Kook Myeong-Cherl , Kim Young Woo , Choi Il Ju
Published: February 2017

106

Background: The aim of this study is to compare the long-term outcomes between patients who underwent endoscopic submucosal dissection (ESD) and those who underwent surgery for early gastric cancers (EGCs) turned out to be out-of-indication of ESD. Methods: We retrospectively reviewed database on gastric cancer patient cohort who underwent ESD or surgery from 2004 to 2014. Patients whose lesions revealed to be out-of-indication for endoscopic resection after ESD or surgery were included in the analysis after 1:1 propensity score matching for baseline clinicopathologic characteristics. Overall survival (OS) and gastric cancer recurrence rates were compared between the matched ESD and surgery groups. Results: After propensity score matching, a total of 193 pairs of patients were included, and 126 pairs were ESD with additional operation group and 67 pairs were ESD without additional operation group. OS (5-year OS rates, 89.5% vs. 89.9%; P=.105) and gastric cancer recurrence rates (5-year recurrence rates, 2.6% vs. 1.6%; P=.080) were not different between the ESD and the matched surgery group. In the matched subgroups, ESD with additional operation group had comparable OS and gastric cancer recurrence rates in comparison with matched surgery group. However, ESD without additional operation group had significantly shorter OS (5-year OS rates, 76.8% vs. 86.3%; P=.032) and higher gastric cancer recurrence rates (5-year recurrence rates, 11.9% vs. 0%; P=.002) than matched surgery group. ESD without additional operation was also significant risk factor for overall mortality and gastric cancer recurrence in multivariate analyses. Conclusions: Patients who did not undergo additional operation after ESD for EGCs turned out be the out-of-indication had worse long-term outcomes. Additional operation should be recommended, when EGC was identified to be the out-of-indication after ESD.
Efficacy and safety of endoscopic resection for gastric subepithelial tumors.
Authors: Jung Kyoungwon , Ahn Ji Yong , Kim Do Hoon , Gong Eun Jeong , Cho Charles J. , Na Hee Kyong , Lee Jeong Hoon , Jung Kee Wook , Choi Kee Don , Song Ho June , Lee Gin Hyug , Jung Hwoon-Yong , Kim Jin-Ho
Published: February 2017

107

Background: Because small gastric subepithelial tumors (SETs) less than 2.0 cm might have malignant potential, ambiguous cases should be removed for optimal diagnosis and treatment. With the recent advances in endoscopic technique, endoscopic resection (ER) has been attempted for pathologic confirmation of gastric SETs. Herein, we aim to investigate the clinical usefulness and safety of ER of gastric SETs. Methods: A total of 115 subjects who underwent ER for gastric SETs from January 2005 to December 2014 were eligible for the study at the Asan Medical Center, Seoul, Korea. Patient’s demographic status, tumor related factors, procedure related factors, and clinical outcomes were retrospectively reviewed by using electronic medical record. Results: Among the 115 patients, 53 were male (46.1%) and the mean age was 51.59 ± 14.59 years. The mean size of all tumors was 18.58 ± 10.71 mm. Complete endoscopic resection was achieved in 108 of 115 tumors (93.9%). The final histopathologic diagnoses included 38 gastrointestinal stromal tumors (GISTs) (33.0%), 21 heterotopic pancreas (18.3%), 18 neuroendocrine tumors (15.7%), 11 leiomyoma (9.6%), 10 inflammatory fibroid polyp (8.7%), and others tumors (n = 17, 14.8%). Perforations occurred in 12 patients (10.4%) and they were successfully managed with endoscopic clipping. Severe bleeding during endoscopic resection occurred in 13 patients (11.3%) and they were treated by endoscopic management. Six patients underwent sequential wedge resection or gastrectomy of stomach because of non-curative resection and the pathologic evaluation revealed residual tumors in 3 patients. There was no recurrence or metastasis during mean follow-up of 44.96 ± 32.62 months (range 3-120.7 months). The rate for complete resection in relation to the final pathology was lower in GISTs (86.8%) than others (97.4%, p = 0.026). The rate of perforation was significantly higher for the fundus (66.7%) than for other locations (0% for the cardia, 16.7% for high body, 8.3% for mid body and 8.3% for antrum) (p < 0.001). Conclusions: ER of gastric SETs may be feasible and safe method for pathologic confirmation and further strategy.
Course and predictors of postoperative outcomes in older patients with localized gastric adenocarcinoma treated preoperatively.
Authors: Charalampakis Nikolaos , Xiao Lianchun , Elimova Elena , Shimodaira Yusuke , Shiozaki Hironori , Das Prajnan , Matamoros Aurelio , Sagebiel Tara L. , Blum Mariela A. , Lee Jeffrey H. , Bhutani Manoop S. , Weston Brian , Mansfield Paul F. , Minsky Bruce D. , Badgwell Brian D. , Ajani Jaffer A.
Published: February 2017

132

Background: Older patients with localized gastric adenocarcinoma (LGAC) suffer from substantial postoperative morbidity and mortality; however, postoperative outcomes in older patients who have received preoperative chemotherapy and/or chemoradiation have not been reported. Our study examined the impact of age and other covariates on baseline, surgical and postoperative characteristics and explored potential predictors of postoperative outcomes. Methods: Patients with LGAC who were treated with chemotherapy (n = 36; 18%) and/or chemoradiation (n = 167; 82%) followed by surgery (n = 203) were grouped in 2 categories by age: 1) ≥ 65 years old (n = 70) and 2) < 65 years old (n = 133). The short-term outcomes included postoperative morbidity and mortality, and the long-term outcomes overall survival (OS) and progression-free survival (PFS). Potential predictors of 90-day postoperative outcomes were identified i) by age group and ii) by a number of other covariates. Descriptive statistics and survival analyses were utilized. Results: The 90-daypostoperative morbidity rate was similar in older and younger patients(61 vs 58%; p = 0.6549). The 90-day mortality rate did not differ statistically between the two groups (3 vs 0%; p = 0.1178). Although major Clavien grade III/IV complications after surgery were more common in older patients, this difference did not reach statistical significance (17 vs 12%; p = 0.3919). The long-term outcomes in terms of OS and PFS were also similar (p = 0.8629 and p = 0.558 respectively). The effect of patient age and ECOG PS on outcomes was not significant. Instead, other factors, such as Charlson comorbidity index (p = 0.0114), length of hospital stay (p = 0.0009), median operative time (p = 0.006) and presence of diabetes (p = 0.0282) were strong predictors of postoperative complications. Conclusions: Our data demonstrate that older patients with LGAC who received preoperative therapy had similar outcomes with younger patients but were more likely to demonstrate higher morbidity, although the differences were not statistically significant. Comorbidity indices provided more information than age in identifying postoperative short and long-term outcomes.
Survival analysis in gastric cancer patients of the Colombian coffee zone at the Oncologos del Occidente clinic during 2014.
Authors: Rojas Uribe Gustavo A. , Martinez Jose , Calvache Jaime
Published: February 2017

148

Background: The risk of death for gastric cancer in Colombia is lightly higher for 2013 compared to 1998. Even though Risaralda has an irregular pattern for the risk of death, it was also higher compared to 1998, for these reasons the survival analysis was made with the information of gastric cancer patients treated in Oncólogos del Occidente clinic during 2014. Methods: A cohort study was made whose exposure is the treatment of gastric cancer. The time variable is the interval between the first medical appointment and the final control, interview or date of death, and the outcome makes reference to a death attributable to cancer gastric or surviving. The source of the cases were the clinical histories found in SAHICO data base, of the patients attended in the clinic Oncólogos del Occidente, to make univariate and bivariate analysis using Stata software. Results: There were 173 patients, from which 69.9% were male; the age group with highest incidence was 60 to 69 years old group (32.2%); 21.38% of the patients had family members with gastric cancer and 53.1% were diagnosed during advanced stages (III-IV). As far as the survival analysis, it was 207 days long, lessen if the patient only receives palliative treatment (122 days long) and increasing if surgery, chemotherapy and radiotherapy were done (252 days long). Conclusions: In a national and international level, the epidemiological data correlates with the findings in this study; with respect to the diagnosis, in Colombia, it is made during advanced stages, meanwhile in developed countries the diagnosis is made during earlier stages because of the screening tests. The oncological surgery increased the patient’s survival, also for the patients who underwent surgery when they received chemotherapy or radiotherapy.
Prognostic value of 18F-FDG PET/CT metabolic tumor volume for complete pathologic response and clinical outcomes after neoadjuvant chemoradiation therapy for locally advanced esophageal cancer.
Authors: Venkat Puja , Oliver Jasmine A , Jin Will , Dault Joshua , Frakes Jessica M. , Hoffe Sarah E. , Pimiento Jose Mario , Almhanna Khaldoun , Fontaine Jacques , Pena Luis , Latifi Kujtim
Published: February 2017

150

Background: The prognostic value of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) has not yet been defined in locally advanced esophageal cancer (LAEC). This study aims to elucidate the prognostic role of PET/CT for patients treated with neoadjuvant chemoradiation (CRT) followed by esophagectomy. Methods: We retrospectively evaluated patients with LAEC treated from 2006 to 2014 with neoadjuvant CRT followed by esophagectomy. 86 patients had pre-CRT and post CRT PET/CT scans performed at our institution. These scans were imported into an image analysis program. PET parameters maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), mean standardized uptake value (SUVmean), and peak standardized uptake value (SUVpeak) were recorded for both pre-CRT and post-CRT scans. MTV was defined using a previously described liver method. The correlation of these parameters with pathologic complete response (pCR) and clinical outcomes was analyzed using binomial logistic regression and cox regression. Results: Pre-CRT MTV < 33.6 (median value) was significantly predictive of pCR (p = 0.019, OR = 3.064). An ROC curve was produced to determine a binary cutoff of 35.8, yielding a higher specificity (62.3% vs. 59%) and the same sensitivity (72.7%), increasing the significance to p = 0.010, OR = 3.378. The ratio of postMTV/preMTV (MTVr) was calculated. MTVr > 0.2857 (median value) was significantly predictive of distant metastasis (DM) after esophagectomy (p = 0.018, OR = 3.680). An ROC curve was produced to determine a binary cutoff of 0.301, which increased specificity from 57.1% to 60.3%, and maintained the same sensitivity at 81.3%, increasing the significance to p = 0.014, OR = 3.815. SUVmax, mean and peak were not predictive. Conclusions: Pre CRT MTV was predictive of pCR and MTVr was predictive of DM. Our data suggests that MTV is superior to SUVmax, mean and peak in predicting for response to treatment in LAEC. Further study is needed to determine if Pre CRT MTV and change in MTV can help define which patients will most benefit from esophagectomy and/ or adjuvant chemotherapy.
Recurrence patterns and outcome of patients with stage IIIB-IV(M0) gastric cancer after gastrectomy and adjuvant chemotherapy: A retrospective analysis in one Chinese cancer center.
Authors: Du Chun-Xia , Zhou Hai-Tao , Zhong Yu-Xin , Pei Wei , Yu Yue , Zhou Ai-Ping
Published: February 2017

160

Background: Gastric cancer is one of the leading causes of cancer-related death in China. Previous data showed 5-year OS rates varied from 10% to 20% in patients with stage IIIb and IV(M0) disease. This study aimedto explore recurrence patterns and outcome of stage IIIB-IV(M0) gastric cancer patients who underwent radical gastrectomy and adjuvant chemotherapy in the Cancer Hospital, Chinese Academy of Medical Center. Methods: Patients with stage IIIB-IV(M0) (AJCC V6) gastric adenocarcinoma were enrolled. All patients received a total or subtotal gastrectomy with at least D1 lymph node dissection. Adjuvant chemotherapy consisting of oxaliplatin, fluoropyrimidines with or without docetaxel was started within 1 month after surgery for maximum of 12 cycles. Results: From January 2006 to December 2011, a total of 137 patients were included (stage IIIB:85, stage IV(M0):52) in the study. The median age was 56 years (20-77) and 96 (70.1%) were male. With a median follow-up time of 40 months, 89 (65%) patients developed recurrence or a second primary malignancy. Peritoneal recurrence (28, 20.4%), locoregional lymph nodes (38, 27.7%) and hematogenous metastases (24, 17.5%) were the most common recurrence patterns. The 5-year DFS rates were 34% and 30% in patients with stage IIIB and stage IV(M0) diseases, respectively. The 5-year OS rates were 46% and 30%, respectively. No statistical difference was observed between stage IIIB and stage IV(M0) patients in terms of median DFS (27.0 m vs 17.4m, p = 0.35). The median OS was in favor of stage IIIB patients compared to stage IV (M0) patients (46.5 m vs 26.1 m, p = 0.02). Multivariate analysis revealed that male (p = 0.02), leather stomach or multiple original diseases (p = 0.02), T4 stage (p = 0.01) and higher lymph node ratio (p < 0.01) were independent negative prognostic factors. Conclusions: Patients with stage IIIB and IV (M0) gastric cancer achieved a better outcome than the historical data in our center. Further investigations are needed to focus on individual and multimodality adjuvant therapy for this group.
Analysis and follow-up of the patients diagnosed with metastatic gastric adenocarcinoma in the Parc Taulí Hospital, Sabadell, between 2010 and 2013.
Authors: Ferrer Marta , Pericay Carles , Macias Ismael , Dotor Emma , Pisa Aleydis , Saigí Eugeni
Published: February 2017

169

Background: The primary endpoint of this study was to know the incidence and treatment of gastric carcinoma in our area. Other secondary endpoints were percentage of treated patients, overall survival (OS), survival in subgroups, and more frequent treatments. Methods: Since 2010 to 2013 all the patients diagnosed with metastatic gastric adenocarcinoma and treated at the hospital Parc Taulí from Sabadell were registered. The clinical information was compiled and analyzed. Survivals curves were determined with Kaplan-Meier functions Results: 168 patients were studied, with 79 metastatic (47%). 56% men and median age 67 years. Localizations were gastric body 52%, gastro-esophageal junction 20%, and antrum 25%. OS of the series was 5,05 months (95% CI, 2,99-7,10). 60% of the patients were treated with first line chemotherapy (CT). From them, 42% had a second line and 25% a third line. DFS were respectively 6,62 months (4,06-9,17), 4,29 months (2,28-6,30), and 2,88 months (1,12-4,64) for every line of treatment. OS of the patients that received chemotherapy was 9.7 months (6,40-13,00). CT more used in first line were triplets of fluropyrimidines, platinum and taxanes, in 45% (21 patients). Also just fluoropyrimidines and platinum without taxanes, in 38%. As a second line the predominant CT is also platinum and fluoropyrimidines (37%), and irinotecan (30%). In third line, 50% are combinations based on irinotecan. Conclusions: The OS of the patients who received CT is significantly prolonged respect the ones who didn’t. The data obtained matches the data already published in the literature, even the more frequent chemotherapy.
Prognostic significance of pre-treatment neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in locally advanced esophageal cancer.
Authors: Clara Joseph A. , Kim Dae Won , Venkat Puja , Frakes Jessica M. , Hoffe Sarah E. , Almhanna Khaldoun , Kothari Nishi , Pena Luis , Pimiento Jose Mario , Kim Richard D.
Published: February 2017

172

Background: The prognosis for esophageal cancer remains poor despite advances in therapeutic modalities. Elevations of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) have been shown to be associated with poorer prognosis in several types of solid cancer. However, their prognostic value remains controversial in esophageal cancer. The aim of this study was to assess the prognostic value of NLR and PLR in esophageal and gastroesophageal junction (GEJ) cancer. Methods: We retrospectively reviewed the database of 77 patients who underwent neoadjuvant chemoradiation and potentially curative resection for esophageal cancer in our institute, between July 2006 and December 2011. NLR and PLR were calculated from laboratory data obtained prior to the start of chemoradiation. The predictive value of NLR and PLR was assessed using Kaplan-Meier curves and Cox regression models for an association with pathologic response to chemoradiation, relapse-free survival, and overall survival. Results: A total of 77 patients were identified with a median age at diagnosis of 62.5 years. In univariate analysis, neither NLR nor PLR were shown to be significantly associated with the pathologic response (p = 0.87, p = 0.89, respectively), relapse-free survival (p = 0.5, p = 0.4, respectively), or overall survival (p = 0.55, p = 0.44, respectively). Conclusions: The present study failed to confirm NLR and PLR as significant predictors of pathologic response to chemoradiation, relapse-free survival, and overall survival in patients with locally advanced esophageal and GEJ cancer undergoing neoadjuvant chemoradiation and surgical resection.
An observational study evaluating the expression of HER2 (1+, 2+, and 3+) with HLA A2/A3+ in gastric adenocarcinoma patients.
Authors: Patnaik Ashis , Parvatini Shyam , Sachdeva Shalabh , Choy Gavin S. , Sharma Akhilesh , Jagannath Palepu
Published: February 2017

18

Background: Gastric cancer remains a major health issue and results in 800,000 annual deaths worldwide. Despite approximately 50% of the gastric and gastroesophageal (GE) junction adenocarcinomas are diagnosed with resectable disease, 40% of disease recurrence is observed in 24 months. While trastuzumab has shown to increase overall survival in HER2 IHC3+ metastatic disease, no current therapies are available for low expressing, or IHC 1+ or 2+ patients. NeuVax (nelipepimut-S) is an immunogenic peptide epitope derived from the extracellular domain of HER2/nu protein administered in combination with rhGM-CSF. NeuVax binds to HLA-A2 and A3 on tumor and antigen presenting cells (APC) and elicits a proliferation of CD8+ (cytotoxic) T-cell immune response against HER2 expressing cancer cells. A proof of concept clinical study will be conducted to assess the effectiveness of nelipepimut-S to prevent recurrence and increase disease free survival in gastric cancer patients with all levels of HER2 expression with HLA A2+/A3+. This prospective observational study was undertaken to estimate the HLA A2/A3+ and HER2 expression status in the Indian population. Methods: Tumor tissue samples from gastric or GE junction adenocarcinoma patients were collected from S. L. Raheja Hospital, Mumbai, India. A serum sample was collected for HLA testing by quantitative PCR. IHC (DAKO, 1:600 dilution) was employed for detection of HER2. All patients were consented for the study. Results: Of the 50 patients evaluated, 12 (24%) were positive for HER2 (1+, 2+, 3+) with HLA2/A3 alleles, meeting the defined projected clinical protocol population of all levels of expression of HER2 and HLA A2+ and/or A3+. Of the 12 patients, 9 (75%) and 3 (25%) expressed HLA A2 and A3, respectively, with no patient demonstrating HER2 3+ expression. Conclusions: Results from this prospective observational study suggest patients with gastric and GE junction adenocarcinoma have HLA A2+ and/or A3+ expressing tumors with mostly HER2 1+, 2+ expression. The estimated incidence of HER2 3+ expression in this population may be limited by size of current study. Results will inform the screen failure rate of the planned Phase 2 clinical study.
Resected pancreatic cancer (PC): Impact of adjuvant therapy (Rx) at a high-volume center (HVC) on overall survival (OS).
Authors: Mandelson Margaret T , Picozzi Vincent J.
Published: February 2017

191

Background: Surgical outcomes for resected PC are known to be superior at HVCs. However, the impact of adjuvant (Rx) performed at HVCs is less studied. We examined the impact of site of adjuvant Rx administration on our resected patients (pts). Methods: Eligible pts were diagnosed 2003-2014 and resected at HVC. Pts were excluded for neoadjuvant Rx, synchronous cancer, death/lost to follow-up within 3 months or contraindications (e.g. morbidity) to adjuvant Rx.. Pts were also excluded if they refused adjuvant treatment or if a community oncologist (CC) was not identified in the medical record or in the western Washington population-based cancer registry. Pt and tumor characteristics were compared in univariate analysis and survival was calculated from date of diagnosis to death or last follow-up. Five year OS was estimated by the Kaplan Meier method and compared using Cox proportional hazards modeling to evaluate the impact of HVC adjuvant Rx on OS while adjusting for potential confounding factors. Results: 245 pts were eligible for study: 139 (57%) treated at HVC, 106 (43%) treated at CC. HVC and CC pts were similar with respect to stage and tumor size, nodal status, resection margins and average distance travelled to HVC. They differed by age (HVC: 63.1, CC: 68.2 p < 0.01). Median and 5-yr OS was 36 mos and 33%. Median OS for HVC vs CC was 44 mos vs. 28 mos (p < 0.01), and 5yr OS was 38.6% vs. 24.8% (p < 0.01), adjustment for age did not alter our findings. Conclusions: 1) With respect to adjuvant Rx for resected PC, HVC and CC pts differed with respect to age only. 2) Both median and 5- yr OS was statistically superior at HVC vs CC. 3) Our study supports the use of HVCs for all Rx components for PC treated with curative intent. 4) Ongoing investigation of patterns of care and their impact on OS in PC is warranted.
Clinical outcomes of patients enrolled in clinical trial compared with patients outside clinical trial in advanced gastric cancer.
Authors: Han Jaejoon , Kim Jin Won , Kim Se Hyun , Lee Jeong-Ok , Kim Yu Jung , Lee Keun-Wook , Kim Jee Hyun , Bang Soo-Mee , Lee Jong Seok
Published: February 2017

21

Background: Participation in clinical trials gives patients with cancer a chance to receive potential benefits, such as experimental treatment, meticulous follow-up and toxicity managements. We aimed to assess the evidence that such an effect exists in patients with gastric cancer. Methods: Clinical characteristics and overall survival of patients with metastatic or recurrent gastric cancer who received fluoropyrimidine and platinum combination palliative chemotherapy within or outside clinical trials at tertiary referral hospital from January 2010 to December 2012 were retrospectively analyzed. Results: Of the 244 patients, 84 patients (34%) were enrolled in clinical trials. During the study period, 20 patients in four phase 3 trials, 54 patients in eight phase 2 trials and ten patients in two phase 1 trials were participated in clinical trials. Twenty patients (8%) at first-line and 64 patients (38%) at second-line or later were enrolled in clinical trials. Younger age (P = 0.014), metastatic disease (P = 0.015) and HER2 IHC status (P = 0.005) were correlated with participation in clinical trials. The median overall survival of patients who participated in clinical trials at first-line was better than those who did not participated in clinical trials, although it was not statistically significant (16 months and 11 months, respectively, P = 0.407). Number of participation in clinical trials was not associated with survival outcome (1 versus ≥ 2 trials: 15 months and 18 months, respectively, P = 0.545). Second-line chemotherapy was administered in 167 patients. The median overall survival of patients who participated in clinical trials at second-line or later was also better than those who did not participated in clinical trials, however, it was not statistically significant (9 months and 6 months, respectively, P = 0.101). Conclusions: Younger patients, metastatic disease, positive HER2 IHC status, and clinical setting of second-line or later were associated with more participation in clinical trials. The median overall survival was numerically longer in patients who were enrolled in the clinical trials although it was not statistically significant.
Irinotecan and infusional 5-fluorouracil (mFOLFIRI) in patients with refractory advanced pancreas cancer (APC): A single institution experience.
Authors: Bupathi Manojkumar , Ahn Daniel H. , Ciombor Kristen Keon , Wu Christina Sing-Ying , Mikhail Sameh , Goldberg Richard M. , Noonan Anne M. , Stephens Julie , Reardon Josh , Hays John L. , Bekaii-Saab Tanios S.
Published: February 2017

215

Background: Pancreatic adenocarcinoma is the fourth leading cause of cancer with a very dismal prognosis. Recently, MM-398 (nanoliposomal irinotecan) was shown to be associated with significant improvement in progression free survival (PFS) and overall survival (OS) with acceptable toxicities when combined with 5-Fluorouracil (5FU)/ leucovorin (LV) compared to 5-FU/LV alone in patients failing one line of gemcitabine-based therapy. There is a paucity of data evaluating the role of irinotecan in combination with 5FU in APC. Methods: We performed a retrospective analysis of all patients who received mFOLFIRI (minus bolus 5FU and LV). All patients with metastatic disease who had failed at least one line of gemcitabine-based therapy prior to receiving mFOLFIRI were included in this study. Descriptive statistics were used to assess the continuous variables and adverse events (AEs) and Kaplan-Meier methods were used to calculate the median PFS and OS. Results: Forty patients were included in this analysis, 33% male. Patients had received 1 to 5 lines of prior therapy (27% with 1 prior and 25% with more than 3 lines of prior therapy). The mean age at diagnosis was 60 and 97% had ECOG of 1. The average CA 19-9 at the start of therapy was 33168 U/ml. The median PFS (from the start of FOLFIRI to disease progression or last follow up) was 2.59 months [95% confidence interval (CI); (1.90, 3.54)] and OS (from the start of FOLFIRI to death or least follow up) was 4.75 months [95% CI (3.14, 8.98)]. The most common AEs included fatigue (98%), neuropathy (83%), anorexia (68%), nausea (60%) and constipation (55%). Grade 3 toxicities included fatigue (13%) and rash (3%). There were no observed grade 4 toxicities that were observed. Conclusions: In this single institution retrospective analysis, mFOLFIRI was found to be both tolerable and relatively effective in this heavily pretreated patient population with APC. Future prospective studies should consider evaluating the role of mFOLFIRI in refractory APC.
Impact of sarcopenia evaluated using the total psoas area (TPA) in patients undergoing Y-90 radioembolization for hepatocellular carcinoma (HCC).
Authors: Ioannides Pericles , Abuodeh Yazan , Jin Will , Hoffe Sarah E. , Frakes Jessica M. , Kim Richard D. , Choi Junsung , El-Hadda Ghassan E. , Biebel Benjamin , Kis Bela , Sweeney Jennifer , Friedman Mark , Kothari Nishi , Anaya Daniel A. , Latifi Kujtim
Published: February 2017

217

Background: Severe skeletal muscle depletion, or sarcopenia, is an independent predictor of clinical outcomes in multiple gastrointestinal cancers. This marker of nutritional status has been defined using the TPA which is measured on a single cross sectional CT image at the L4 vertebral body level. We sought to evaluate whether TPA was predictive of outcomes in those patients with unresectable HCC receiving Y-90 radioembolization. Methods: In an IRB approved database consisting of HCC patients treated with Y-90 radioembolization, 111 patients met our selection criteria of treatment from 2009-2014. To be eligible for the study, patients were included prior to their first injection of Y-90 if they had CT imaging available that included the L4 vertebral level that could be transferred to the treatment planning software system. Of these, 73 patients met criteria and were included in the final analysis. The L4 vertebra was identified on axial CT imaging and the psoas muscle was manually contoured bilaterally. Sarcopenia was defined by the presence of the psoas area in less than the median of the cohort. Results: Sarcopenia was associated with a significantly decreased overall survival (p = 0.013) The mean age of the cohort was 67.6 years (range, +/- 9.45) consisting of 84% male and 16% female patients. Difference in age or gender did not correlate significantly with survival. The median survival time in the “low” (sarcopenic) group was 10.46 months (range, +/- 1.21), whereas the median survival in the “high” group was 18.02 months (range, +/-4.26). The median survival for the entire cohort was 12.86 months. OS at 30 months was 15.4% in the sarcopenic group and 30.2 % in the “high” group. TPA in the upper quartile was associated with a survival benefit compared to the bottom quartiles. The presence of sarcopenia was associated with an increased risk of mortality (HR = 2.049; p = 0.015 CI: 01.150, 3.649). Conclusions: Measurement of the psoas area using TPA is a simple objective method to detect frailty and is predictive of overall survival outcome following Y-90 radioembolization
A multi-center study of 349 pancreatic mucinous cystic neoplasms: Preoperative risk factors for adenocarcinoma.
Authors: Postlewait Lauren McLendon , Ethun Cecilia G. , Merchant Nipun B. , Parikh Alexander A. , Idrees Kamran , Hawkins William G. , Fields Ryan C. , Weber Sharon M. , Cho Clifford Suhyun , Martin Robert C. G. , Scoggins Charles Raben , Bentrem David J. , Kim Hong Jin , Ahmad Syed A. , Abbott Daniel Erik , Kooby David A. , Maithel Shishir Kumar
Published: February 2017

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Background: Pancreatic mucinous cystic neoplasms (MCN) are defined by presence of ovarian stroma per WHO 2000 classification. Given their malignant potential, current guidelines recommend resection. However, there are limited data on preoperative risk factors for adenocarcinoma (AC) and high grade dysplasia (HGD) occurring in an MCN. Methods: MCN resections from 2000-2014 at the 8 institutions of the Central Pancreas Consortium were included. Patients with and without AC/HGD were compared. Primary aims were to determine preoperative risk factors for AC/HGD in an MCN and to assess outcomes of MCN-associated AC. Results: Of 1667 resections for pancreatic cystic lesions, 349 pts (21%) had an MCN with 52 (15%) having MCN-associated AC/HGD. Male gender (29 vs 8%; p<0.001), head/neck location (39 vs 13%; p<0.001), increased MCN size (7.2 vs 4.6 cm; p=0.004), radiographic presence of a solid component/mural nodule (54 vs 20%; p<0.001), and duct dilation (43 vs 12%; p<0.001) were associated with AC/HGD compared to benign MCN. All persisted as independent predictors of MCN-associated AC/HGD (Table). AC/HGD was not associated with presence of radiographic septations or preoperative cyst fluid analysis (CEA, amylase, or mucin). Median CA19-9 for patients with AC/HGD was 210 vs 15 U/ml for those without (p=0.001). In the 44 pts with AC, 41 (93%) had lymph nodes harvested with nodal metastases in only 14 (34%). Median FU for pts with AC was 27 mos. AC recurred in 12 pts (27%) with a 3-yr RFS of 59%. OS for pts with MCN-associated AC was 64% at 3 yrs. Conclusions: Adenocarcinoma or high grade dysplasia is present in 15% of resected pancreatic mucinous cystic neoplasms. Pre-operative factors associated with AC/HGD in an MCN include male gender, head/neck location, larger MCN, solid component/mural nodule, and duct dilation on imaging. MCN-associated AC appears to have decreased LN involvement and increased RFS and OS compared to typical pancreatic ductal adenocarcinoma. [Table: see text]
Effect of regorafenib on angiogenesis in neuroendocrine tumors in vitro.
Authors: Milosavljevic Tanja , Juge Elise , Reeks Adrianne , Owens Jennifer , Wang Yi-Zarn , Boudreaux J Philip , Woltering Eugene
Published: February 2017

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Background: Regorafenib, a potent multikinase inhibitor, targets a broad range of receptor tyrosine kinases (RTKs), including but not limited to VEGFR, PDGFR, and FGFR, which play an integral role in angiogenesis. Human neuroendocrine tumors (NETs) rely on RTKs to mediate tumor neovascularization, development, and metastasis. Similar kinase inhibitors like PTK787 profoundly inhibit angiogenesis in human NETs. We hypothesized that Regorafenib would have antiangiogenic and antitumor effect on human NETs. This study demonstrates inhibitory activity of Regorafenib on pathologic angiogenesis in vitro using our human tumor angiogenesis model (HTAM). Methods: Human NETs were collected in cell culture media in the O.R. and transported to the laboratory at 4⁰C. Tumors were minced into 2 mm fragments, embedded in a fibrin-thrombin clot and supplemented with a nutrient culture media. Neovessels were visually scored and evaluated based on three parameters: percent initiation, angiogenic growth, and overall angiogenic response. An effective concentration was selected for all successive HTAM assays based on dose response experiments. Angiogenesis data was obtained for 77 patients and analyzed for significance using paired samples t-test (MedCalc). Results: Dose-dependent inhibition of angiogenesis was observed for all NETs (n = 77): primary tumors (n = 11), lymph nodes (n = 28) and organ (n = 38) metastases. Selected dose of Regorafenib [1100 nM] achieved statistically significant inhibition of angiogenic growth (59%) and overall angiogenic response (44.5%) in all NETs (p < 0.0001). However, there was no significant inhibition of percent initiation for all NETs except in primary tumors (p = 0.0260). Conclusions: Regorafenib is an effective antiangiogenic agent for NETs in-vitro. Regorafenib targets angiogenic growth in all NETs and inhibits initiation of angiogenesis exclusively in NET primary tumors. This suggests preferential use of Regorafenib for NET patients who have not yet developed metastases. Alternatively, Regorafenib could be an effective adjuvant treatment for advanced stage patients.
Radiosensitivity differences between liver metastases based on primary histology suggest implications for clinical outcomes following SBRT.
Authors: Ahmed Kamran A. , Caudell Jimmy J. , El-Haddad Ghassan , Berglund Anders E. , Hoffe Sarah E. , Frakes Jessica M. , Eschrich Steven A. , Torres-Roca Javier
Published: February 2017

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Background: Increasing evidence in the management of oligometastases with stereotactic body radiotherapy (SBRT) reveals differences in outcomes based on primary histology and dose selection. We have previously identified a multigene expression index for tumor radiosensitivity (RSI) with validation in multiple independent cohorts. In this study, we assessed RSI in liver metastases and our clinical outcomes following SBRT based on primary histology. Methods: Patients were identified from our institutional IRB approved prospective observational protocol. A total of 444 metastatic liver lesions were obtained from a de-identified meta-data pool. Gene expression was from Affymetrix Hu-RSTA-2a520709. The RSI 10 gene assay was run on tissue samples and calculated using the previously published algorithm. A cohort of 33 patients with 38 liver metastases treated with SBRT using 50 Gy or 60 Gy in 5 fractions was used for clinical correlation. Results: The median RSI for all liver lesions was 0.42 (Q1, 0.28; Q3, 0.49). The most common primary histology for liver metastases were colorectal (n = 374; 81%), pancreas (n = 18; 4%), and breast (n = 15; 3%). There were significant differences in RSI of liver metastases based on histology. The median RSIs for liver metastases in descending order of radioresistance were skin (0.54), colorectal (0.43), stomach (0.43), pancreas (0.42), lung (0.35), breast (0.34), small intestine (0.22), and anal (0.21); p = 0.0003. A total of 57 patients had multiple liver tissue samples. When averaging RSI values from the same patient, significant differences continued to be noted based on primary histology: colorectal (0.43), lung (0.43), breast (0.34), and anus (0.20); p = 0.008. The 12 and 24 month Kaplan-Meier rate of local control (LC) for colorectal lesions was 79% and 59% compared to 100% for non-colorectal lesions (p = 0.019), respectively. Conclusions: In this first analysis assessing the radiosensitivity of liver metastases, we find significant differences based on primary histology. As we move towards an era of personalized radiation delivery, this study suggests primary histology may be an important factor to consider in SBRT dose selection.
Clinical utility of circulating tumor DNA (ctDNA) in resectable pancreatic ductal adenocarcinoma (PDAC).
Authors: Wong Hui-Li , Bushell Kevin , Karasinska Joanna , Arthur Sarah , Morin Ryan , Schaeffer David F. , Renouf Daniel John
Published: February 2017

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Background: ctDNA is emerging as a promising biomarker, with potential utility in screening, detecting minimal residual disease after curative resection and monitoring treatment response or resistance in advanced disease. Most PDAC studies to date have focused on identifying mutant KRAS ctDNA in metastatic disease. Here we perform sequential ctDNA quantification in patients (pts) with resectable PDAC using a novel and highly sensitive multiplex technology to explore the clinical utility of ctDNA as a diagnostic and prognostic biomarker. Methods: Banked plasma and tumor samples from 18 pts with resected PDAC were retrieved. Plasma samples were collected 0-28 days before, and 28-70 days after surgery. DNA was extracted using standard protocols and analyzed using the OnTarget system, which enriches for DNA molecules containing hot spot mutations prior to sequencing. A 96-plex panel that includes the most prevalent mutations in KRAS, PIK3CA and TP53 was used. Results: 16 pts (89%) had at least 1 mutation detected by OnTarget in the tumor sample, most frequently in KRAS codon 12 (n = 14). ctDNA was detected in the pre-operative blood sample in 7/16 pts with tumor mutations (sensitivity 44%) and 0/2 pts without detectable tumor mutations (specificity 100%). Of the 10 pts with available post-operative blood samples, 1 did not have a tumor mutation. 4 pts had detectable ctDNA, 3 of whom have recurred. In contrast, 0 of the 5 pts without detectable post-operative ctDNA have recurred. At median follow-up of 37 weeks, recurrence-free survival (RFS) was significantly longer in pts without detectable ctDNA after surgery (median not reached vs 9 weeks, p = 0.022). Of 11 plasma samples with detectable ctDNA, 3 harbored mutations that were not detected in the primary tumor, including 2 non-KRAS mutations (GNAS R201H and PIK3CA E542K). Conclusions: Pre-operative ctDNA has low sensitivity, suggesting limited utility in PDAC screening. RFS was significantly longer in pts without detectable post-operative ctDNA; however this analysis is limited by small numbers and short follow-up. Discordance in hot spot mutations detected in tumor and matched plasma was observed in 27% of samples, possibly related to intratumoral heterogeneity.
Association of long-term survival in pancreatic cancer (PDAC) with increased proliferative and anti-apoptotic protein activation.
Authors: Picozzi Vincent J. , Ramos Corinne , Hoke Nicholas N , Hoke Glenn D.
Published: February 2017

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Background: 5 year (yr) overall survival (OS) for resected PDAC is typically 20%. To test the potential for molecular prediction of > 5 yr OS in such patients (pts), we analyzed proteomic activation (phosphorylation) patterns in both cancer and stromal cells from initial surgical specimens prior to adjuvant therapy (Rx). Methods: Formalin-fixed, paraffin-embedded tissue from 40 pts (20 pts each with long-term actual disease-free OS [median 65 mo, range 26-137 mo] [LTS] and with early relapse/death < 2 yrs [STS]) with de novo resected PDAC formed the test cohort. All pts received adjuvant Rx (chemo Rx with/without chemoradiation). Laser Capture Microdissection enabled directed cancer and stromal cell isolation. Retrospective blinded protein activation analysis for both was performed via Reverse Phase Protein Array (RPPA). Differences in baseline protein signaling of LTS vs. STS were evaluated via two-way ANOVA analysis. Results: Analysis of > 50 signal transduction proteins (STPs) for activation (phosphorylation) showed these significant differences for LTS vs. STS in cancer cells: 1) Activation of proliferation markers Sox2/ Ki 67 were higher (p<0.0001). 2) Activation of anti-apoptotic signal transducer and activator of transcription 3 (p-STAT 3) ( p=0.047) and p-SRC kinase (p=0.039) were higher. 3) Activated p-m-TOR expression was higher (p=0.021). 4) Activation of mitotic marker histone H3S10 was lower (p=0.03). In stromal cells, activation of the survival marker Mek S298 was lower (p=0.021). For other STPs, differences for LTS vs. STS (e.g. Livin, PCNA) were not seen. Conclusions: 1) LTS and STS of de novo resected PDAC show clear differences in cancer cell protein activation re key markers of proliferation and apoptosis (Sox2, Ki67, STAT3, SRC kinase, H3S10). 2) For stromal cells, protein activation was largely similar, but a difference in activation of one stromal protein (Mek S298) was seen. 3) For these pts, differences in protein activation prior to adjuvant Rx could enhance current prognostic models and/or identify new pharmacological targets designed to improve OS. 4) These findings require further validation: a second 60 sample validation cohort is now under anaylsis.