bluuebunny/crossref_metadata_2025 huggingface dataset:
Response to neoadjuvant chemoradiation in rectal cancer: Experience from the national cancer institute of Peru.
Authors: Muro Johanny F , Veliz Karin , Maldonado Mike M , Flores Claudio J. , Montenegro Paola Catherine
Published: September 2018

e15157

Background: Preoperative Chemoradiation (CRT) in rectal cancer has benefit in local control. 50 - 60% of cases are down-staged and 20% achieve a pathologic complete response (pCR). Despite the fact that there is no a clear benefit in long-term outcomes, response to preoperative treatment could have a prognostic value. Our objectives were to determine the pCR and down-staging (DS) rates after neoadjuvant CRT, as well as disease free survival (DFS), overall survival (OS) and prognostic factors associated with these outcomes Methods: Patients with rectal cancer treated with preoperativefluoropyrimidine based CRT at the National Cancer Institute of Peru (INEN) from 2007 to 2012 were evaluated. OS and DFS were calculated according to Kaplan-Meyer method. The survival curves were compared using the Log-rank or Breslow test. Multivariate analysis was performed with Cox regression Results: 282 patients were included, median age was 62 years (range 18-93), female: male ratio (1:1). Clinical stages were as follows: I, 13.8%; II, 32.3% and III, 52.9%. Median follow up was 5 years. Patients received capecitabine and 5-FU during radiotherapy in 75.5% and 24.5% of cases respectively. Sphincter preserving surgery was possible in 46% of cases. In patients who underwent surgery, DS and pCR rates were 52% and 10.8%, respectively. Patients who achieved pCR were predominant female and had CEA less of 5 ng/mL. In multivariate analysis, clinical stage, DS, type of fluoropyrimidine (capecitabine) and surgery were associated with OS. 5 year DFS and OS was 54.9% and 60.5% respectively in patient that underwent surgery Conclusions: DS rate achieved at our institution is within the range reported by the literature and is associated with an improvement in OS. Our pCR rate was lower than what has been reported, this might be related to great proportion of patients with advanced clinical stage (EC III) in our study. This patient could have benefit with totally neoadjuvant Chemoradiation.
Can CRM status on MRI predict survival in locally advanced rectal cancers: Experience from the Indian subcontinent.
Authors: Anam Jay Rashmi , Chandarana Mihir , Arya Supreeta , Desouza Ashwin Luis , Ostwal Vikas S. , Engineer Reena , Patil Prachi , Saklani Avanish
Published: September 2018

e15167

Background: Neoadjuvant chemoradiation has become the standard approach for treatment of locally advanced rectal cancers. Magnetic Resonence Imaging (MRI) is the staging modality of choice in rectal carcinoma. Recent reports have studied the impact of MRI on local recurrence and survival both in treatment naïve and post treatment settings Methods: A retrospective analysis of prospective database was performed over a period of 1 year. All pretreatment patients with carcinoma of rectum were included in the study. The status of CRM on MRI was compared to that on the histopathology and as a predictor of recurrence and survival. For analysis, the MRI scans done for patients at presentation were labeled as MRIT. This included all patients irrespective of further treatment received. Patients who were treated with NACTRT had two MRI scans. The MRI at presentation in this subset of patients was labeled as MRI1 and the reassessment MRI after NACTRT was labeled as MRI2. Thus, MRI1 represented a subset of MRIT with locally advanced tumors treated with NACTRT. All the sets of MRI scans were analyzed separately for prediction of CRM involvement and for their effect on local recurrence and survival rates. Results: 221 patients were included with a median follow-up 30 months. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MRIT, MRI1 and MRI2 to predict CRM status were 50%, 62.3%, 96.5%, 5.6% and 61.8%, 50%, 55%, 95%, 6% and 54.7% and 77.8%, 63.7%, 98%, 11%, 64.5% respectively. On multivariate analysis pathological positive margins alone predicted a poor overall survival (OS) whereas involved CRM on pathology and pretreatment MRI predicted poorer disease free survival and OS Conclusions: CRM status on pathology remains the most important prognostic factor to impact overall survival, disease free survival and local recurrence. CRM status on MRI at presentation alone has significant impact on disease free survival and local recurrence. Although MRI done after neoadjuvant treatment may not predict survival, it has a role in helping modify the surgical approach with a goal to achieve a negative CRM on pathology.
Preemptive versus reactive management of EGFR rash among mCRC patients treated with panitumumab: Results of a national survey of treating oncologists in the United States.
Authors: Lowe Kimberly , Hool Kristina , Garawin Tamer , Bergstresser Rachel , Kafatos George , McNamara Michelle , Collins Seth , Bach Bruce A.
Published: September 2018

e15169

Background: The Skin Toxicity Evaluation Protocol with Panitumumab (STEPP) and the Japan Skin Toxicity Evaluation Protocol with Panitumumab (J-STEPP) were open-label, randomized trials that were designed to evaluate differences in preemptive versus reactive management of dermatologic toxicities associated with panitumumab among patients with mCRC. The objective of this study was to evaluate if there were differences in the knowledge and application of STEPP and J-STEPP among oncologists who self-identified as primarily managing EGFR rash preemptively or reactively. Methods: A total of 250 practicing oncologists who had treated at least three new or continuing mCRC patients with panitumumab in the last year completed an online survey to report their opinions and perceptions regarding the management strategies for mCRC patients who are treated with panitumumab. Preemptive treatment was described in the survey as beginning treatment “prior to the appearance of rash” and reactive treatment was defined as beginning treatment “after signs of rash.” Results: Of the 250 oncologists who participated in this study, n = 58 (23%) reported treating 100% of their patients preemptively and n = 38 (15%) reported treating 100% of their patients reactively. A significantly higher proportion of preemptive treaters than reactive treaters reported following the skin management strategies from STEPP or J-STEPP when managing panitumumab-related skin toxicity (31% vs 13%, p = 0.02). When asked if skin moisturizer, sunscreen, over-the-counter topical steroids, prescription topical steroids, oral antibiotics, topical antibiotics, or UV protective garments were most critical in the preemptive management of panitumumab-related skin toxicity, preemptive treaters more likely to report using oral antibiotics and reactive treaters more like to report using sunscreen (p = 0.05). Conclusions: The results of this survey highlight the wide variability in the management of EGFR-related rash among mCRC patients who are treated with panitumumab and they highlight the need for heighted education among oncologists who treat mCRC patients with panitumumab.
Cost-utility analysis of panitumumab use compared with cetuximab and bevacizumab for the first-line therapy of wild-type RAS metastatic colorectal cancer in the Peruvian health system.
Authors: Milton Valderrama , Apolaya-Segura Moises , Montenegro Paola Catherine
Published: September 2018

e15171

Background: To estimate the cost-utility of Panitumumab compared to Cetuximab (Erbitux®) and Bevacizumab (Avastin®) for the first-line therapy of metastatic colorectal cancer in the Peruvian health system Methods: A cost-utility analysis was performed using a Markov's model based in epidemiological parameters, metastatic colorectal cancer (mCRC) associated costs, and the efficacy of therapy using specific monoclonal antibodies against wild-type RAS mCRC. The costs of biological agents were estimated from the payers' viewpoint, using a 3.5% discount rate. The model includes the transition between five health states (mCRC, surgery, remission, progression, and death), and each cycle lasts for one month in a 3-year temporal horizon Results: The results of the model indicate that Bevacizumab and Panitumumab were cost–effective compared with Cetuximab. Therapy using Bevacizumab for a three-year period cost PEN 178,950.96 less than Panitumumab, but generated 0.91 less QALYs. The incremental cost-effectiveness ratio (ICER) showed that Cetuximab had extended dominance when compared to Panitumumab and Bevacizumab. This means that Panitumumab is more expensive, but it leads to a greater clinical benefit. Conclusions: Using the best published data available, these results suggest that the clinical effectiveness of Panitumumab and Bevacizumab translates into a favorable cost-utility ratio; and it particularly generates savings. The use of Panitumumab is associated to a longer survival, more QALYs gained and more months in remission.
The prognostic value of systemic inflammatory factors in patient with metastatic gastric cancer.
Authors: Manikhas Georgy M. , Beliak Natalia P. , Kutukova Svetlana I. , Zhukova Natalia V. , Popova Natalia V. , Erdniev Sanal
Published: September 2018

e15505

Background: Inflammation seems to be significant factor in carcinogenesis and tumor progression of numerous cancers. Blood calculated neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), C-reactive protein (CRP), lactate dehydrogenase (LDH), international normalized ratio (INR) can be evaluated as systemic inflammation markers and prognostic biomarker for many aims: survival outcomes, lymph node metastasis and recurrence, treatment responses in a variety of cancers. The purpose of this study was to investigate baseline associations between blood test parameters (NLR, PLR, LDH, CRP, INR) and their prognostic biomarker role for patient with metastatic gastric cancer, undergoing first-line chemotherapy Methods: Potential baseline inflammatory markers (platelets, neutrophils, lymphocytes, the platelet-lymphocyte ratio, the neutrophil-lymphocyte ratio, the serum C-reactive protein [CRP], the serum LDH, INR) were retrospectively analyzed in 32 patients with metastatic gastric cancer, IV stage (median of age – 60,50). Multivariate analyses were used to identify prognostic factors for overall survival (OS). Baseline values were compared with tumor characteristic and median survival times (MSTs). Results: Multivariate analysis identified due to Cox proportional-hazards regression showed significant longest OS in patients with: localization of primary tumor in antral part of gastric (HR 0,45, 95% CI 0,25-0,80, p = 0,0065); low baseline’s level of WBC (HR 1,17, 95% CI 1.02 - 1,35, p = 0,0219); low baseline’s level of neutrophil (HR 1,18, 95% CI 1.02 - 1,34, p = 0,0251). Level of LDH, CRP, INR didn’t show significant ratio for this cohort of patient. Peritoneum metastatic also didn’t significant affect on OS in patient with metastatic gastric cancer. Patients with low baseline’s platelet to lymphocyte ratio (HR 1,004, 95% CI 1,0009-1,0072, p = 0,0125) and low (from 0 to 3,0) neutrophil to lymphocyte ratio (HR 1,81, 95% CI 1,09-2,99, p = 0,0212) had a significantly longest OS time. Conclusions: Inflammatory markers can predict overall survival in stage IV gastric cancer. Simple and useful.
Advanced signet ring cell type gastroesophageal cancers in Central American patients age 40 and below: A summary of one tertiary care center's experience and a review of the literature.
Authors: Cannon Timothy Lewis , Ershler William B. , Bijelic Lana , Nizam Amanda , Hosseini Neda
Published: September 2018

e15515

Background: Gastric Cancer mortality rates in Central and South America are among the highest in the world. Our institution has monitored a cohort of patients who have presented with metastatic gastroesophageal cancer, age 40 or below. Methods: After observing multiple cases of advanced gastric cancer in young immigrants from Latin America, we performed a retrospective cohort study at Inova Fairfax Hospital, a 1000 bed tertiary care center in Northern Virginia. We reviewed our cancer registry from 2013-2016, to identify all patients, age 40 or below, with stage IV gastric adenocarcinoma. We also reviewed the percentage of hispanic patients in our cancer registry for all cancer diagnoses, for comparison. Results: There were thirteen patients with stage IV gastric cancer who were aged 40 or below found in our registry. Ten of the thirteen patients (76.9%) were from Latin America (see Table 1), with the majority of those being from either El Salvador or Honduras. All thirteen cases were notable for signet ring cell differentiation. Hispanic patients make up only 8.3% of the total subjects and 12.9% of gastric cancer subjects in the Inova Fairfax Hospital Cancer registry during that same time period. Conclusions: Stage IV signet ring cell gastric cancers have occurred frequently at our tertiary care center among young patients from Latin America. Further exploration of epidemiological risk factors is warranted. [Table: see text]
A pyrolytic compound of curcumin, a dietary deketene curcumin to inhibit gastric carcinogenesis in a mouse model.
Authors: Yoshida Taichi , Inoue Masahiro , Fukuda Koji , Shimizu Kazuhiro , Taguchi Daiki , Shibata Hiroyuki
Published: September 2018

e15518

Background: Gastric cancer is the second cause of cancer death in the world, killing more than 700,000 people in 2012. The risk factors are Helicobacter pyloriinfection, obesity, smoking, consumption of red meat or alcohol. However, an effective preventive measure of this disease has bot been established. Curcumin, a dietary pigment, that has been used for more than three thousand years, has an anti-tumor potential. However, bioavailability of curcumin is very poor, and it is not used in clinics. Researchers are trying to overcome this short point. To synthesize a new analog bearing higher anti-tumor potential is our solution, and we have successfully developed a series of new diarylpentanoid analogs. Our diarylpentanoid analogs are structurally different from curcumin, a diarylheptanoid. Recently, a breakthrough finding that a deketene curcumin is formed as a result of pyrolysis of curcumin during cooking of curry, was published. This deketene curcumin is identical to one of our analogs, 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one, named GO-Y022. For this reason, we investigate the efficacy and safety issues of GO-Y022 in a mouse gastric cancer model. Methods: We assessed anti-tumor potential of GO-Y022 on gastric cancer cell lines, KATO Ⅲ, H-111-TC, GCIY and SH-10-TC. We also examined the potential to inhibit β-Catenin and pSTAT3 levels. We conducted mouse experiment using transgenic mouse model overexpressing Wnt signaling, COX2 and Prostaglandin E2. This mouse is highly seceptible to gastric carcinogenesis. We orally administrated GO-Y022 mixed with food. We checked the safety issues of the treated mouse, and measured the tissue concentration of GO-Y022 by HPLC method. Results: GO-Y022 can inhibit the growth of gastric cancer cell lines significantly. The average IC50value of GO-Y022 was 5.05 ± 0.93 μm. That is about five times lower than curcumin. This potential was confirmed in mice. Blood concentration and the tissue distribution of GO-Y022 were negligible except gastrointestinal epithelia. GO-Y022 was safe for mouse models. Conclusions: GO-Y022 can inhibit the growth of gastric carcer in vivo. Oral administration of GO-Y022 can suppress gastic cancer topically.
Clinical significance of serum tumor marker for advanced gastric cancer with palliative chemotherapy: A retrospective study.
Authors: Zhu Yahui , Liu Baorui , Wei Jia , Du Juan , Yang Ju , Yang Yan , Wang Kangxin , Yang Yang , Zou Zhengyun
Published: September 2018

e15524

Background:The predictive value of tumor markers has been previously reported a lot. However, the studies focused on advanced gastric cancer are few. In this study, we tried to investigate the relationship between the tumor markers of advanced gastric cancer and clinical characteristics, therapeutic effect of chemotherapy, and prognosis. Methods:A retrospective study including 146 advanced gastric cancer who had not received any previous anticancer therapy was performed. Blood samples for CEA, AFP, CA125, CA72-4, CA242 and CA19-9 were taken from patients before chemotherapy and monthly during their treatments. Statistical analysis was performed to predict the clinical value of these tumor markers. Results:CEA yielded an ROC value of 0.621 in predicting lymph node metastasis in gastric cancer, which was significantly higher than any of other markers. CA125 had the highest sensitivity, specificity and accuracy in gastric cancer patients with peritoneal metastasis. AFP and CEA were more frequently positive in patients with hepatic metastases. The response rate of Decreasing group, Stable group and Increasing group based on CA19-9, CEA, CA72-4, CA125 and CA242 levels achieved statistical significance. Positive cases of CA125, CA242, CA19-9 and CA72-4 showed poor prognosis, and significant differences in 3 year-survival rates were observed for CA125 and CA242. Conclusions:We found that different tumor markers in gastric cancer indicated different metastasis sits. CEA, CA242, CA19-9, CA125 and CA72-4 are predictive biomarkers in evaluating the effectiveness of chemotherapy. The elevated CA125, CA242, CA19-9 and CA72-4 levels at diagnosed had association with shorter overall survivals, especially CA125 and CA242.
Apatinib to enhance chemosensitivity of gastric cancer to paciltaxel and 5-fluorouracil.
Authors: Cheng Xiangdong , Xu Zhiyuan , Chen Jiahui , Zhang Chunli , Yu Jianfa , Teng Fei , Zheng Guowei , Lv Hang
Published: September 2018

e15545

Background: Patients (pts) with late-stage gastric cancer (GC) have a poor prognosis. Targeted agent combined with chemotherapy is expected to yield clinical benefits. Apatinib, a novel tyrosine kinase inhibitor targeting VEGFR-2, improves outcomes in patients with metastatic GC as a third line of treatment. Hence, we aimed to assess the efficacy and safety of apatinib plus chemotherapy in vivo and in vitro. Methods: The MGC803 cell viability was assessed by CCK-8 assay, and the interactions between apatinib and conventional cytotoxic agents revealed by combined index (CI) values were calculated using Calcusyn 2.0 software. We also used a zebrafish embryo xenograft model to validate the synergistic interactions. Furthermore, 4 pts with late-stage GC were enrolled to receive paclitaxel (PTX)/S1 chemotherapy plus apatinib in conversion surgery. Apatinib was administered 500 mg once a day continuously, PTX 130 mg/m2 was given on day 1, and S-1 was administered at 80 mg/m2for 14 consecutive days, followed by 7 days of rest. Treatment was administered for 3-5 cycles, but the last cycle did not include apatinib. Results: Apatinib showed synergistic interactions with both PTX and 5-Fu in vivo (CIs < 1). The zebrafish embryo xenograft model also demonstrated that addition of 0.25 µg/mL apatinib significantly enhanced the tumor growth inhibition effects of 25 (38.39% vs. 11.77%, P < 0.001) and 50 ng/fish (43.58% vs. 17.88%, P < 0.05) 5-Fu, as well as those of 0.75 ng/fish (53.62% vs. 35.22%, P < 0.001) and 1.5 ng/fish (59.71% vs.46.73%, P < 0.01) PTX. Apatinib plus S1/paclitaxel chemotherapy was well tolerable before surgery. Objective response to preoperative SPA treatment was achieved in all pts. No posteroperative bleeding event or wound-healing complication was observed. No postoperative mortality occurred and morbidity was encountered. Pathological examination showed that all pts had grade Ib pathological response. Conclusions: The experimental data suggested that apatinib improves the efficacy of PTX and 5-Fu both in vitro and in vivo. Clinical evidence showed that combination of PTX/S1 chemotherapy with apatinib has promising efficacy and acceptable safety profile in late-stage GC, especially in the conversion surgery.
Analysis of contrast-enhanced CT textures to predict survival of patients with primary esophageal cancer treated with definitive chemotherapy and radiation therapy.
Authors: Wang Qifeng , Lang Jinyi , Li Tao , Lv Jiahua , Cao Bangrong , Fan Yu , Wang Yi , Xiao Miyong
Published: September 2018

e15559

Background: To determine the association between tumor heterogeneity, morphologic tumor response, and overall survival in primary esophageal squamous cell cancer (ESCC) treated with chemotherapy and radiation therapy (CRT). Methods: After an institutional review board waiver was obtained, 57 clinical stage III patients with CRT were analysis. All patients underwent contrast-enhanced CT before RT and after RT 40Gy between 2012 and 2015 were analyzed in terms of whole-tumor texture, with quantification of entropy, uniformity, max and mean gray-level intensity, kurtosis, standard deviation of the histogram, mass and skewness for fine to coarse textures (filters 1.0-2.5, respectively). Whole-tumor texture was analyzed using IBEX 1.0β. The association between texture parameters and survival time was assessed by using Kaplan-Meier analysis and a Cox proportional hazards model. Results: The median, 1 and 3 years overall survival (OS)were 20.2 months 75.4% and 32.1% .Only the clinical factor posttreatment volume (median OS, 28.4 vs 14 months; P = 0.016), pretreatment median entropy of 0.069 or greater (median OS, 31.6 vs 17.0 months; P = 0.022), and medium max gray-level intensity of 11 or greater (median OS, 33.2 vs 11.7 months; P = 0.034),Coarse kurtosis of 58.4122 or greater (median OS, 28.4 vs 15.0months; P = 0.036) were associated with improved survival time. Survival models that included a combination of pretreatment entropy and posttreatment volume. We used a 3-point risk classification index with equal weights given to entropy and volume predict OS and progression-free survival (PFS). The median OS for high-, medium-, and low-risk groups were12.2, 19.1, and 31.7 months,respectively (P = 0.013). Validated the risk model in PFS, The median PFS for high-, medium-, and low-risk groups were 8.0, 18.5, and not received months,respectively (P = 0.043). Conclusions: Pretreatment texture parameters are associated with survival time, and the combination of pretreatment texture parameters and post volume performed better in survival models.
Racial differences of iron deficiency anemia in gastric cancer.
Authors: Perimbeti Stuthi , Correa Erika , Degen Kathleen , Hanson Shaun Bryan , Lee William May , Hou Kevin Ye , Jain Maneesh Rajiv , Ward Kristine Marie , Styler Michael , Nandi Neilanjan
Published: September 2018

e15564

Background: One of the six domains of health care quality identified by the Institute of Medicine in 2001 was equitable care.1 While disparities in cancer are often expressed in terms of mortality, comorbidities such as iron deficiency anemia (IDA) that can be caused by less comprehensive or less timely treatment of gastrointestinal malignancies also impact quality of life and may be considered as a metric of equitable care. Methods: Using data from the Healthcare Cost and Utilization Project (HCUP), total numbers of U.S. admissions with gastric cancer listed as primary diagnosis were recorded for each year between 1999-2014. The subset of these numbers with IDA listed as a secondary diagnosis were recorded to derive a prevalence of IDA within this gastric cancer population. The relative rate of African American and Hispanic IDA prevalence were compared to Caucasians for each year. Within each ethnic subset, cost, length of stay, and inpatient mortality were compared. Results: The relative rate of iron deficiency in gastric cancer for African Americans versus Caucasians was 1.745 and for Hispanics versus Caucasians was 1.665. Hospital cost by ethnic group: Caucasians $55,359, African Americans $62,020, Hispanics $83,914. Length of stay in days by ethnic group: Caucasians 9.13, African Americans 10.12, Hispanics 10.17. Inpatient mortality by ethnic group: Caucasians 4.51%, African Americans 4.02%, Hispanics 2.29%. All values were significant (p < 0.05). Conclusions: African American and Hispanic populations are at increased risk of iron deficiency anemia in the setting of gastric cancer as compared to Caucasians. This was associated with increased cost and length of stay to a lesser degree. Surprisingly, Caucasians still demonstrated the highest mortality rate, followed by African Americans and Hispanics. This suggests that though ethnic disparities are still evident as of 2014 they may not accurately reflect mortality but still continue to impact morbidity. As this comorbidity impacts quality of life, it may be a target for future metrics or interventions.
Regulatory-T cells (Tregs) in tumor infiltrating lymphocytes (TILs) from patients with advanced gastric cancer (AGC) after chemotherapy containing ramucirumab.
Authors: Kotani Daisuke , Togashi Yosuke , Kawazoe Akihito , Doi Toshihiko , Nishikawa Hiroyoshi , Shitara Kohei
Published: September 2018

e15570

Background: Vascular endothelial growth factor-A (VEGF-A) and VEGF recepter-2 (VEGFR-2) axis is known to induce Tregs in tumor bearing mice. Ramucirumab (RAM), a monoclonal antibody for VEGFR-2, was recently approved for patients with AGC. However, little is known about the influence of RAM on Tregs in TILs from AGC patients. Methods: Patients with AGC who had been planned to receive chemotherapy containing RAM were prospectively enrolled for this study from January 2016 to August 2016. Paired samples were obtained from primary tumor at pre- and post-RAM therapy to analyze immune profiles of TILs using flow cytometry assay. Results: A total of 17 patients were analyzed. Median age was 68 years old (range, 46-79). All patients received one or more previous chemotherapy. RAM containing regimens included RAM+paclitaxel (n = 13), RAM monotherapy (n = 3) and RAM+irinotecan (n = 2). FOXP3highCD45RA-CD4+ T cells (effector Tregs: eTregs) in CD4+ T cells was significantly decreased after RAM therapy compared with that in baseline (mean, 19.5% vs.13.6%, P = 0.036). In contrast, no significant change of CD8+ T cells was observed (mean, 36.7% vs. 36.0%, P = 0.86). Expression of programmed cell death-1 (PD-1) on CD8+ T cells was tended to be decreased after RAM therapy. Conclusions: eTregs in TILs was suggested to be decreased after RAM-containing therapy which warrants further evaluation in a larger cohorts. This observation might be a rationale to use RAM as an immunomodulator in combination of immune checkpoint inhibitors for AGC.
A personalized, web-based prognostic tool for resectable gastric cancer.
Authors: Jabo Brice , Morgan John W. , Aljehani Mayada A. , Selleck Matthew J , Lin Albert Y.
Published: September 2018

e15575

Background: Gastric cancer (GC) mortality remains high, with a 5-year survival of 30 percent. For patients with resectable GC, mortality varies depending on both patient and tumor characteristics. The current study sought to develop a web-based prognostic model to assist patients and health care providers in decision making regarding either surgery-only or adjuvant chemoradiotherapy (CRT). Methods: California SEER data was used and records, including demographic, pathologic, and treatment information, for 2,583 patients diagnosed with stage IB to III GC and treated with either surgery only or adjuvant CRT from 2006 to 2013 were retrieved. Purposeful selection using Cox regression model was used to identify important mortality predictors. Additionally, with simple random sampling, 70% of the data were assigned to the training set and the remaining 30% were assigned to the test set. Furthermore, generalized boosted classification model was trained using the training set and validated using the test set. Area under the curve (AUC) of the receiver operating characteristic (ROC), sensitivity, specificity and accuracy were determined for 5- and 10-year mortality. Results: The median survival was 33 months for patients in the training set, and 32 for the test set. Predictors included in the model were age, ethnicity (Asian/other, Hispanic, non-Hispanic black and non-Hispanic white), T-stage, histology (intestinal, diffuse and other), presence of signet ring (yes/no), proximal location (yes/no), lymph node ratio, and CRT following surgery (yes/no). Validation of the model on the test set showed as follows: AUC, sensitivity, specificity and accuracy of 0.78(95%CI = 0.75,0.82), 0.75, 0.65 and 0.70 for 5-year survival and 0.77(95%CI = 0.74,0.80), 0.79, 0.55 and 0.70 for 10-year survival. Conclusions: The proposed web-based prognostic tool using readily available patient and tumor characteristic provides validated and personalized prognostic information to aide clinicians and patients in GC adjuvant treatment decision process. [Table: see text]
Survival impact of adjuvant regimens for advanced gastric cancer after radical D2 resection in a Peruvian population.
Authors: Rioja Patricia Elizabeth , Enriquez Daniel , Pacheco Christian , Morante Zaida , Guevara Andres , Castro Victor , Montenegro Paola Catherine , Payet Eduardo
Published: September 2018

e15576

Background: The benefit of chemoradiotherapy(CRT) or chemotherapy (CT) for gastric cancer with high metastatic lymph node involvement after complete radical D2 resection is still controversial, previous studies had reported better disease free survival (DFS) but no differences in overall survival (OS). Our aim was to compare DFS and OS between CRT and CT. Methods: Retrospectively, 201 medical records were reviewed from patients with advanced gastric cancer (nodes +ve) after complete radical D2 resection between 2008 and 2012 at Instituto Nacional de Enfermedades Neoplasicas (Peru). Patients received CRT (5FU and RT as Macdonald’s protocol) or CT (capecitabine 2g/m2/14days + oxaliplatin 135mg/m2/day1 q21d for 6months). We describe clinical and pathological characteristics, DFS/OS with univariate and multivariate cox analysis were performed. Results: Mean age was 54.4years [19-83] and 17.9% were < 40years. Distal localization (46%), high histological grade (69.7%) and poorly cohesive subtype (38.3%) were most frequent characteristics among patients, 140(69.7%) and 130(64.7%) were T4 and N3, respectively. From 201 patients, 134 underwent to CRT and 67 to CT, with no clinical differences between groups. We observed a significant higher nodal ratio in CT group (0.27 vs 0.35, p = 0.009). 69.5% patients completed treatment with CRT, while only 54.5% in CT (p = 0.04). At 5years median of follow-up, 66 (49.3%) and 26(38.8%) recurrences were documented in CRT and CT groups, respectively. Median DFS were 19 and 23 months in CRT and CT group (HR:1.04, 95%CI:0.7-1.4, p = 0.8), while median OS were 25 and 26 months, respectively (HR:1.07, 95%CI:0.75-1-5, p = 0.6). At multivariate analysis, higher T stage and nodal ratio were associated to worse DFS, and patients who completed treatment were associated to better DFS (HR:0.59, 95%CI:0.4-0.8, p = 0.004). Higher T stage and nodal ratio had significant negative impact on OS. Conclusions: We found a benefit of CT over CRT in gastric cancer with high metastatic lymph nodes, however in our population it was not statistically significant, indeed further larger clinical trials are needed. In this study, higher T stage and nodal ratio were associated to worse prognosis.
Effect of long non-coding RNA EIF3J-AS1 on multi-drug resistance and autophagy in gastric cancer.
Authors: Luo Yuhao , Zhou Rui , Huang Na , Sun Li , Liao Wangjun
Published: September 2018

e15581

Background: Gastric cancer (GC) is a leading cause of cancer mortality worldwide, oxaliplatin and epirubicin based chemotherapy are one of the most important treatment options for GC patients. However, drug resistance, especially multi-drug resistance remains a major obstacle for successful chemotherapy. Recently, long non-coding RNAs (lncRNAs) have been widely identified to play emerging roles in diverse physiological and pathophysiological processes including drug resistance. Our previous bioinformatics analysis showed long non-coding RNA EIF3J-AS1 was a potential multi-drug resistance gene, but the underlying mechanism is still unknown. Methods: We generated oxaliplatin resistance cells (MGC803/OXA) and epirubicin resistance cells(MGC803/EPI) based on parental gastric cancer cells MGC803. Relative expression levels of EIF3J-AS1 were measured by qRT-PCR. Transmission electron microscopy was used to measure autophagosomes. Rapamycin was applied to inducing autophagy while chloroquine and 3-methyladenine were used to block autophagy. Protein level of autophagy related genes were examined by Western Blot. Coexpression genes of EIF3J-AS1 from TCGA RNA-seq datas were analyzed by cBiportal. RNA immunoprecipitation was used to analyze endogenous microRNAs and mRNAs. Results: EIF3J-AS1 was significantly upregulated in MGC803/OXA and MGC803/EPI cells compared with parental cells MGC803. EIF3J-AS1 inhibition increased chemosensitivity to both oxaliplatin and epirubicin. Moreover, EIF3J-AS1 silence lead to the decrease of autophagy. Autophagy related gene ATG14 was identified as a downstream target gene. EIF3J-AS1 promoted ATG14 expression by directly interacting with and increasing stability of ATG14 mRNA, On the other hand, EIF3J-AS1 competitively sponged miR-188-3p and promoted ATG14 expression in a ceRNA-dependent way. Conclusions: LncRNA EIF3J-AS1 is a crucial regulator of multi-drug resistance by inducing autophagy in gastric cancer. Targeting EIF3J-AS1/ATG14 axis might be a new paradigm for cancer therapeutics.
ERBB pathway alterations in advanced gastric signet-ring cell carcinoma (SRCC) and the implications for targeted therapy.
Authors: Wei Jia , Xu Bo , Jin Shenying , Yu Lixia , Liu Baorui
Published: September 2018

e15586

Background: Studies have shown that ERBB3 mutations are associated with poor clinical prognosis and ERBB3 targeted therapeutics can be effective against ERBB3 mutant-driven tumors. ERBB signal pathway plays a very important role in the initiation and progression of gastric cancer, however the ERBB2 expression and mutation rate is relative low especially in gastric SRCC. Thus, ERBB3 might be a promising target for the treatment in SRCC patients. The aim of this study is to speculate the prognostic and targeted therapy value in gastric SRCC by evaluating the mutation rate and type of ERBB3. Methods: 92 patients with histological diagnosis of advanced gastric SRCC were retrospectively selected. ERBB3 mutation was evaluated by next generation sequencing from formalin-fixed paraffin-embedded (FFPE) samples. ERBB2 expression was tested by immunohistochemistry. Correlations between ERBB2/3 status and clinical pathologic characteristics and overall survival (OS) were performed. Results: All of the 92 patients were diagnosed as local advanced or metastatic gastric SRCC (92.4% were stage III, 7.6% were stage IV). All the patients received 5-FU-based first-line chemotherapy. 14 out of all 92 patients were ERBB3 mutated SRCC, in which only 2 samples were ERBB2 positive. 12 of all the 14 mutations were in the extracellular domain, 2 were in the transmembrane region. There was no correlation between ERBB3 mutation and serosa invasion (P = 0.389) or lymph node metastasis (P = 1.000). The median OS was 20.5 months (95% CI = 10.05to 30.95 months) for patients with ERBB3 mutation, and 19.0 months (95% CI = 15.54 to 22.46 months) for patients without ERBB3 mutation (P = 0.567). There was no difference in OS according to HER2 positive or negative in ERBB3 mutated patients (14.8 months vs 20.5 month, P = 0.374). Conclusions: Our study demonstrated 15.2% of gastric SRCC patients harboring ERBB3 mutation, providing a potential subgroup of gastric SRCC for targeted treatment on ERBB pathway. No difference of OS was observed, probably due to the relative small sample size and low ERBB2 positive rate in SRCC patients. Further investigation on ERBB3 is warranted to clarify mechanisms of ERBB pathway in gastric SRCC.
Radical esophagectomy for thoracic esophageal squamous cell carcinoma followed by adjuvant radiotherapy with or without chemotherapy: Which is more beneficial?
Authors: Tu Yan , Peng Feng
Published: September 2018

e15597

Background: The current guidelines of the National Comprehensive Cancer Network for thoracic esophageal squamous cell carcinoma(TESCC) are commended no additional treatments after surgery unless the margins are positive.The optimal therapeutic options in TESCC initially treated after surgery remains controversial .This retrospective study compared the efficacy and side effect profile between postoperative adjuvant radiotherapy(RT) and chemoradiotherapy(CRT) in stage II or III TESCC patients who underwent curative esophagectomy. Methods: From January 2006 to December 2013 , 272 cases with pathological confirmed stage II or III TESCC, who had undergone complete esophagectomy, were eligible for analysis.Of these patients, 148 cases received postoperative CRT–at least 2 courses of cisplatin plus fluorouracil or paclitaxel– while the other 124 cases received RT(≥45Gy) alone.The primary end point was overall survival (OS) and the secondary endpoint were disease free survival (DFS) and toxic reactions. Results: In CRT and RTgroups,the OS rates at 1, 3 and 5 years were 91.8% vs 83.8% , 51.3% vs 31.5% and 25% vs 9.68% , respectively(P < 0.01).In CRT and RTgroups, the median OS were 39 months (95% CI, 31.6 to 46.3 months) and 30 months (95% CI, 21.0 to 38.9 months), respectively(P = 0.213), and the median DFS were 23 months (95% CI, 14.7 to 31.3 months) and 16 months (95% CI, 13.3 to 18.6 months),respectively(P = 0.155). Univariate and multivariate analyses showed stage, N stage and the number of lymph nodes removed were independent prognostic factors for OS. There were no statistically differences between the two groups for both recurrence and metastasis rates(P > 0.05). Toxic reactions, including myelosuppression and gastrointestinal reaction, were significantly more common in the CRT group than in the RT group (P < 0.05). No significant differences in incidence of other toxic reactions were found between the two groups. Conclusions: Our results indicate that, in stage II or III TESCC patients, compared with postoperative RT,CRT has a tendency to improve survival. Toxic reactions were more common with CRT than with RT alone, but patients could tolerate CRT.
The PD-1, PD-L1 expression and CD3+ T cell infiltration in relation to outcome in advanced gastric signet-ring cell carcinoma, representing a potential biomarker for immunotherapy.
Authors: Jin Shenying , Xu Bo , Yu Lixia , Fu Yao , Wu Hongyan , Fan Xiangshan , Liu Baorui , Wei Jia
Published: September 2018

e15609

Background: Recent data supports a potentially significant role for immune checkpoint inhibitors in the treatment of gastric cancer. However, there are few data on the clinical implications of immunotherapy markers in gastric signet-ring cell carcinoma (SRCC). We evaluated the expression of programmed cell death protein-1 (PD-1), programmed cell death ligand 1 (PD-L1), infiltration by CD3+ T cell, microsatellite instability (MSI), and Epstein-Barr Virus (EBV), and the relationship of each factor to survival in SRCC patients. Methods: SRCC samples from 89 patients were stained by immunohistochemistry to evaluate PD-L1, PD-1, CD3+ T cells, and MSI. EBV was detected by DNA in-situ hybridization. Results: All 89 patients had advanced gastric SRCC (89.9% were stage III, 10.1% were stage IV). All patients received 5-FU-based first-line chemotherapy. PD-L1 and PD-1 were expressed in 40.4% and 18.0% of the patients, respectively. There was a significant correlation between PD-L1 and PD-1 expression (r = 0.363, p < 0.001). There was loss of at least 1 of the 4 DNA mismatch repair (DNA-MMR) gene proteins in 32.6% of samples. However, there was no association between the expression of PD-L1, PD-1 or MSI status to overall survival (OS). Only 1 case out of 89 was EBV positive, with concurrent PD-L1 positivity, a high degree of CD3+ T cell infiltration and MSI. Increased CD3+ T cells numbers was associated with increased PD-1 expression (r = 0.256, p = 0.012) and MSI status (r = 0.208, p = 0.05). High CD3+ T cell infiltration was related to better OS (23.7 months, 95% CI: 19.0-38.0 vs 15.8 months, 95% CI: 13.0-22.0, p = 0.033), but was not an independent prognostic factor for survival after multivariate analysis (HR = 0.68, 95% CI: 0.42-1.10, p = 0.116). Conclusions: CD3+ T cell was more infiltrated in PD-1 positive, tumors with MSI and were associated with better OS, indicating an adaptive immune resistance may be occurring. Further research into the cancer characteristics and immunotherapy markers of the gastric SRCC immune microenvironment may highlight targets for immunotherapy.
Sorafenib treatment in recurrent hepatocellular carcinoma post liver transplantation.
Authors: Fallah-Rad Nazanin , Cao Yanshuo , Sapisochin Gonzalo , Dhani Neesha C. , Knox Jennifer J. , Grant David , Jang Raymond Woo-Jun , Greig Paul David , Lilly Leslie , Chen Eric Xueyu
Published: September 2018

e15613

Background: Liver transplantation (LT) is a potentially curative treatment for patients (pts) with selective hepatocellular carcinoma (HCC). HCC recurrence post LT is estimated to be 15-20%. Data on systemic therapy post-recurrence is scarce and limited case series suggest that sorafenib (SOR) may have benefit in this population. We reviewed a single center experience with SOR in recurrent HCC post LT Methods: A retrospective review was conducted on pts with recurrent HCC post LT at University Health Network (UHN) who were treated with SOR. Pt characteristics were collected including age, gender, comorbidities, background liver disease, type of LT, and time to recurrence after LT. Treatment information collected included: initial SOR dose (and adjustments), adverse events (AEs), duration of treatment and survival. Results: Between 2006 and 2016, 24 pts were identified. The average age was 60 years (range: 18-72), most pts were male (20/4), living/cadaveric transplant: 11/13. HCC etiology included hepatitis B (10), alcohol (4), NASH (3), hepatitis C (2), hemochromatosis (2), Budd-Chiari (2) and unknown (1). The average time to recurrence of HCC was 16.08 (range: 1.5-60) months post OLT. There was a bimodal time to recurrence with a median of 6 months. SOR starting doses were 200 mg BID in 18 pts, 300 mg BID in 1 and 400 mg BID in 4. 14 pts required dose adjustment due to AEs, mainly relating to fatigue and palmar-plantar syndrome. The median time on treatment was 2.5 (range: 0.25-37) months. The average time to progression on SOR and/or discontinuation due to AEs was 4.30 (+/- 7.2) months. Conclusions: SOR is reasonably tolerated in pts with recurrent HCC post LT, with expected AE profiles. In this small case series, the median time on SOR was short and estimated time to progression was shorter than that in non-transplant HCC population. Overall, SOR has limited activity in this population, but selected pts may derive extended benefit. Better understanding of responders and investigations of other therapies are needed for this population.
CT-based radiomic analysis of hepatocellular carcinoma patients to predict key genomic information.
Authors: West Derek L , Kotrotsou Aikaterini , Niekamp Andrew Scott , Idris Tagwa , Giniebra Camejo Dunia , Mazal Nicolas James , Cardenas Nicolas James , Goldberg Jackson L. , Colen Rivka R.
Published: September 2018

e15623

Background: The utilization of computed tomography (CT) has virtually replaced the need for tissue diagnosis in hepatocellular carcinoma (HCC). Imaging features (e.g. size, shape and vascularity) have been associated with patient survival. However, the full potential of CT in HCC diagnosis may not be reached, as high-throughput computing allows for extraction of quantitative features that are not part of radiologists’ lexicon. The purpose of this study was to investigate the ability of radiomic analysis to successfully identify specific doxorubicin chemoresistant genes on CT images of treatment-naïve hepatocellular carcinoma (HCC). Methods: We identified 27 treatment-naïve patients with a single HCC tumor from The Cancer Genome Atlas (TCGA) whom had gene expression profiles. Baseline CT images were obtained from The Cancer Imaging Archive (TCIA). 3D Slicer software was used for manual tumor segmentation and final segmented images were reviewed by a board-certified radiologist. Following tumor segmentation, texture analysis was performed on MATLAB environment. A total of 310 rotation invariant texture features, which measure tumor heterogeneity, were obtained (first-order histogram and grey level co-occurrence matrix). The mRMR method was used to select the most relevant radiomic features. ROC analysis and LOOCV were used to assess the performance of five specific genes known to confer doxorubicin chemoresistance (TP53, TOP2A, CTNNB1, CDKN2A and AKT1). Results: Radiomic analysis identified TP53 (AUC = 86.61%, Specificity = 92.31%, Sensitivity = 92.9%), TOP2A (AUC = 78.0%, Specificity = 69%, Sensitivity = 85.7%), CTNNB1 (AUC = 86.8%, Specificity = 92.3%, Sensitivity = 85.7%), CDKN2A (AUC = 76.9%, Specificity = 76.9%, Sensitivity = 78.6%) and AKT1 (AUC = 72.5%, Specificity = 69.2%, Sensitivity = 85.7%) in treatment-naïve HCC CT studies. Conclusions: The identification of specific genes that confer chemoresistance to doxorubicin can be reliably ascertained via the use of radiomic analysis. This study may help tailor future treatment paradigms via the ability to categorize HCC tumors on genetic level and identify tumors which may not have a favorable response to doxorubicin based therapies.
Hepatocellular carcinoma outcomes at an academic transplant center: A single-institution retrospective study.
Authors: Kurkul Charles Vincent , Ryer Elizabeth , Maheswaran Abiramy , Holzwanger Erik , Switzer Bradley Alan
Published: September 2018

e15624

Background: Although there have been recent advances in locoregional therapies, liver transplant remains the only curative treatment for hepatocellular carcinoma. Previous single-institution studies suggest that despite aggressive management, OS for non-transplantable patients remains poor. It has been proposed that multidisciplinary evaluation at a high volume academic center will improve outcomes, though this has not been well reported. Methods: 249 patients with diagnosed HCC evaluated in the UMass multidisciplinary HCC clinic between 2006 and 2016 were identified. Patient demographics, interventions, and outcomes were documented through chart review. Kaplan-Meier survival curves were calculated to compare outcomes. Results: Of the 249 patients, 77% were male and the median age was 64 (22-83). Child-Pugh score at diagnosis was 53% A/32% B/13% C. Comorbidities included hepatitis C (54%), hepatitis B (9%), and NASH (1.2%). Alcoholic liver disease was present in 45% of patients (25% HCV+EtOH). The stage at diagnosis was I/II/III/IV in 43/37/16/4% respectively. 101 patients were eligible for transplant. 54 received a liver. 38 remain on the waiting list. In the 169 non-transplant patients, multiple modalities were utilized including resection (3%), Y90 (6%), TACE (40%), RFA (30%), EtOH ablation (1%), and SBRT (19%). 38% of patients received sorafenib, and 3.5% cytotoxic chemotherapy. 40% of patients had one intervention, 21% had two, 16% had three, and 7% had four or more. 16% of patients received only active surveillance. The median OS for all patients was 4.4 years. Transplanted patients had a 5 year OS of 80%. The median OS for non-transplant patients was 36 months. Median OS by C-P in non-transplant patients was 52/24/11 months (A/B/C). Median OS by stage in the same population was NR/32/11/6 months. Conclusions: While patients with very advanced and severe disease still did poorly, this aggressively treated group demonstrated favorable outcomes when compared to the historically poor survival without transplant.This would imply that multidisciplinary treatment in a high volume center improves outcomes. Further prospective and comparative work is pending.