bluuebunny/crossref_metadata_2025 huggingface dataset:
Eosinophilic colitis in cancer patients.
Authors: Khurana Shruti , Abu-Sbeih Hamzah , Ma Weijie , Foo Wai Chin , Zhang Hao Chi Chi , Wang Yinghong
Published: May 2020

e16500

Background: Eosinophilic colitis (EoC) is a rare form of eosinophilic gastrointestinal disease characterized by diffuse eosinophilic infiltration in the deep lamina propria and extensive crypt epithelial injury with apoptosis and crypt abscesses. The pathophysiology is still unclear and associated with many etiologies. We described the clinical characteristics of EoC in cancer patients. Methods: We retrospectively reviewed the pathology report of the colonic samples from endoscopy or surgical resection obtained between 01/2000 and 12/2018 at MD Anderson Cancer Center. The included cases had significant eosinophilia with key word description of “numerous”, “many” or “dominant” on the pathology. Clinical data were collected and analyzed. Results: A total of 41 cases were included based on the inclusion criteria with 34% men, with a median age of 60. 27% had NSAID use and 40% were smokers. One-fourth had co-existing autoimmune conditions. 78% had cancer diagnosis (hematologic at 41%, followed by genitourinary and gastrointestinal origin) with the rest carrying no cancer diagnosis. Half of the cases received chemotherapy with median duration of 180 days between chemotherapy to EoC onset. Common EoC symptoms included diarrhea, and abdominal pain which were present in 76% patients. Diarrhea was more prevalent in patients who received chemotherapy (85% vs 42%). Median duration of EoC symptoms was shorter in cancer patients (240 vs 30 days) and chemotherapy exposure (120 vs 30 days). Hospitalization for EoC was required in 15% cases. Most commonly administered treatment for EoC was immunosuppressants (22%). Normal colonoscopy was reported in 88% patients at the time of EoC diagnosis. All-cause mortality was 37% and was mostly related to underlying malignancy. Conclusions: The disease course of EoC in cancer patients on chemotherapy is not well defined. It appeared to be less severe than non-cancer patients, which raised the possibility of two separate subclasses of this disease entity. Cancer/chemotherapy related EoC could be a GI specific paraneoplastic manifestation, and behave differently from other etiology. [Table: see text]
Mast cells positive to c-kit receptor and to tryptase in normal to cancer pancreatic tissue and the correlation with angiogenesis.
Authors: Laface Carmelo , Ammendola Michele , Zuccalà Valeria , Luposella Francesco , Zizzo Nicola , Patruno Rosa , Porcelli Mariangela , Gadaleta Cosmo Damiano , Tucci Marco , Ranieri Girolamo
Published: May 2020

e16502

Background: In the last years published studies demonstrated that mast cells (MCs) contain pro-angiogenic factors associated with tumoral angiogenesis. Tryptase is the most abundant and potent pro-angiogenic substance contained in MCs secretory granules and it can be released in tumour microenvironment. Up to now few data have been published on the role of MCs in angiogenesis in both pancreatic ductal adenocarcinoma cancer tissue (PDACT) and adjacent normal tissue (ANT). Methods: In this study MCs density positive to C-Kit receptor (MCDP-C-KitR), MCs density positive to tryptase (MCDPT), MCs area positive to tryptase (MCAPT), angiogenesis in terms of microvascular density (MVD) and endothelial area (EA) were evaluated by immunohistochemistry and image analysis in both PDACT and ANT. All tissue samples were obtained from 45 patients with stage T2-3N0-1M0 (by AJCC for Pancreas Cancer Staging 7th Edition) who had undergone surgery. For each analyzed tissue parameter mean ± standard deviation was evaluated in both PDACT and ANT and differences were evaluated by Student t-test. Each analysed tissue parameter was then correlated each other by Pearson t-test analysis. Results: The mean value ± standard deviation (SD) regarding MCDP-C-KitR, MCDPT, MCAPT, MVD and EA in TT was 14.69±4.57, 13.31± 4,23, 171.41±62,39 µ2, 29.11±7.93, 201.82±70.05 µ2 respectively and the mean value ± SD in ANT was 5.61 ± 2.39, 5.13 ± 2.03, 54.43 ± 16.73 µ2, 11.45 ± 4.96, 67.60 ± 21.96 µ2, respectively. Differences in terms of mean value ± SD between PDACT and ANT were significant for each analyzed tissue biomarker (p ranged from 0,001 to 0,004 by t-test analysis; Table). Data demonstrated that MCDP-C-KitR MCDPT, MCAPT, MVD and EA significantly increased from ANT to PCT. In PCT it was showed a correlation between MCDP-C-KitR and MCDPT (r = 0.87, p = 0.01), MCDP-C-KitR and MVD (r = 0.74, p = 0.02), MCDP-C-KitR and MCAPT (r = 0.81, p = 0.01), MCDPT and MVD (r = 0.72, p = 0.02), MCD-C-KitR and EA (r = 0.73, p = 0.02), MCDPT and MCAPT (r = 0.85, p = 0.01), MCAPT and MVD (r = 0.76, p = 0.02), MCAPT and EA (r = 0.66, p = 0.03), MCDPT and EA (r = 0.69, p = 0.03), MVD and EA (r = 0.82, p = 0.01). Conclusions: Our data suggest that assessed tissue parameters increased from ANT to PDACT and that MCs are associated with angiogenesis in PDACT. On this basis inhibition of MCs by tyrosine kinase inhibitors such as masitinib or inhibition of tryptase by gabexate mesylate may be a novel antiangiogenetic approach in pancreatic cancer therapy.
Progression-free survival (PFS) as a surrogate endpoint for overall survival (OS) in advanced/recurrent gastric cancer (AGC) treatment: Individual-patient-data (IPD) based meta-analysis of randomized trials.
Authors: Oba Koji , Paoletti Xavier , Bang Yung-Jue , Bouché Olivier , Ducreux Michel , Michiels Stefan , Moehler Markus H. , Morita Satoshi , Ohashi Yasuo , Sakamoto Junichi , Sasako Mitsuru , Shitara Kohei , Van Cutsem Eric , Buyse Marc E. , Burzykowski Tomasz ,   GASTRIC (Global Advanced/Adjuvant Stomach Tumor Research through International Collaboration)
Published: May 2020

e16506

Background: In 2013, the GASTRIC (Global Advanced/Adjuvant Stomach Tumor Research through International Collaboration) evaluated the surrogacy of PFS based on IPD of 4,069 patients from 20 randomized trials of AGC. Treatment effects on PFS and on OS were only moderately correlated, and we could not validate PFS as a surrogate endpoint for OS. More recent trials, with refined inclusion criteria and higher standards for evaluating progression, may allow for a more accurate estimate of the correlation. The 2nd round of the GASTRIC sought to re-evaluate the surrogacy of PFS for OS in AGC. Methods: The GASTRIC database was updated with trials published after 2010 which used RECIST (Response Evaluation Criteria in Solid Tumors). Since the proportional hazards assumption was questionable for PFS, we primarily used mean-time ratio as a treatment effect measure, estimated by using the log-logistic model. Using the meta-analytic approach, correlations between PFS and OS at the individual level (Rindiv), and between treatment effects on PFS and on OS at the trial level (Rtrial), were estimated using Spearman’s rank-correlation and estimation-error-adjusted regression, respectively. Surrogate threshold effect was estimated as well. Results: We analyzed 10,912 patient data (1st round 4,069 patients from 20 trials and 2nd round 6,843 patients from 17 trials). Overall, moderate correlations were found at the individual level (Rindiv = 0.75, 95%CI = 0.75 to 0.76 in Hougaard copula) and at the trial level (Rtrial = 0.77, 95%CI = 0.32 to 1.00), respectively. Surrogate threshold effect was equal to 1.29, i.e., observing 29% increase in mean PFS time would predict a significant increase of the OS time. In the subgroup of patients with measurable disease in the 2nd round dataset (4,866 patients), Rtrial was higher and equal to 0.93 (95%CI = 0.70 to 1.00), with STE equal to 1.21. These results were same for 1st and 2nd line trials. Conclusions: The meta-analysis indicates a strong correlation between treatment effects (expressed as log-mean-ratios) on PFS and OS in patients with measurable disease.
Genomic and immune intratumor heterogeneity in gastric linitis plastica.
Authors: Huang Jin , Zhao Guofeng , Peng Qiu , Ma Jian , Li Pansong , Chang Lianpeng , Guan Yan-Fang , Reuben Alexandre , Xia Xuefeng , Yi Xin , Zhang Jianjun , Chen Zihua
Published: May 2020

e16518

Background: Gastric linitis plastica (LP) is a rare and aggressive type of gastric cancer (GC) for which the genomic landscape and architecture have gone largely undescribed. Methods: 4 LP patients were enrolled. 10 region tumor samples of each LP patient and matched peripheral blood were collected. Matched blood cells of each patient were also collected for removing germline background Whole-exome sequencing(WES), TCR sequencing, TCGA gastric cancer and several WES articles data were used to investigate intra and inter patient genomic and immune heterogeneity. Results: All 4 LP patients were female and were in stage III. LP biopsies were sequenced with median 290.6x effective depth. A total of 11,504 somatic mutations including 6,339 non-silent mutations were identified. The median non-silent tumor mutation burden (TMB) of biopsy samples was 3.23 mutations/Mb (range from 1.36 to 4.88), which was comparable to gastric adenocarcinoma(p = 0.3). Phylogenetic trees of 4 LP patients demonstrated clear evidence of branched evolution, and the phylogenetic trees varied extensively across the four cases. The percentages of trunk mutations of 4 LP were 12.8%, 5.4%, 5.4% and 30.7%, respectively, while the proportions of trunk neoantigens were 6.2%, 2.2%, 12% and 12.4, respectivelyWhen comparing LP to other multiregion WES studies, e.g., lung adenocarcinoma, renal cell carcinoma, and esophageal squamous cell carcinoma, LP was one of the most heterogeneous tumor types. The top mutational signatures in this cohort associated with spontaneous deamination, DNA mismatch repair (MMR), and small indels at repeats etc. Furthermore, profound TCR ITH was observed in all 4 LP patients. None of the T cell clones were shared among all tumor regions and 94.23-94.41% T cells were restricted to individual tumor regions. To quantify the TCR ITH, we utilized the Morisita overlap index (MOI), which ranged from 0.34 to 0.56 across different regions within the same tumors suggesting marked inter-individual TCR repertoire heterogeneity and profound intratumor TCR heterogeneity. Conclusions: Based on whole-exome sequencing and TCR sequencing, we demonstrate that LP is highly heterogeneous for mutations, neoantigens and T cells, which contributes to its poor prognosis.
Brain metastasis from esophageal squamous cell carcinoma: Clinical characteristics and prognosis.
Authors: Xiao Linlin , Mowery Yvonne Marie , Wang Jun , Zhao Min , Jing Shaowu , Gao Guangbin
Published: May 2020

e16525

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumors in China, but brain metastasis is rare and less reported. The aim of this study is to investigate the clinical characteristics and outcomes of ESCC patients with brain metastasis, so as to provide some references for them. Methods: Between January 1, 2009 and December 31, 2018, 16480 patients with ESCC were registered at the Fourth Hospital of Hebei Medical University. A total of 52 patients (0.32%) were diagnosed of brain metastasis. Thirty-two patients received craniocerebral radiotherapy, of them, 17 cases were treated with radiotherapy alone, the rest were treated with chemotherapy (n = 12) or targeted therapy(n = 13) concurrently. There were 6 patients received chemotherapy (platinum + docetaxel / paclitaxel) alone, and 14 cases received support therapy only. Results: The median interval time from the date of diagnosis of the primary tumor until diagnosis of brain metastasis was 9.2 months (range, 0-249.2 months). The initial stages of the patients in II, III and IV were 6, 25 and 21, respectively. The median length of esophageal tumor was 5.0 cm (range, 2-12cm). Single lesion and multiple foci of brain metastasis were found in 40 and 12 patients, respectively. Twenty-eight patients had extracranial metastasis simultaneously, including lung metastasis in 14 patients, liver metastasis in 13 patients, bone metastasis in 11 patients, and multiple metastases in 16 patients. The median survival was 6.7 months (range, 0.4-43.4 months), the survival rate of 6 months, 12 months and 24 months was 53.8%, 26.9%, and 4.9%, respectively. The median surviva lof craniocerebral radiotherapy group was longer than that of chemotherapy/supportive care group (8.4 months vs 2.9 months, c2= 6.706, P = 0.01). Multivariate analysis demonstrated that craniocerebral radiotherapy (P = 0.008) and Karnofsky (KPS) score (P = 0.027) were significant prognostic factors for survival. Conclusions: Approximately 0.32% of ESCC patients diagnosed or developed brain metastasis since initial registration. A higher KPS score and craniocerebral irradiation were associated with a better survival trend. Craniocerebral radiotherapy should be an importantoption for ESCC patients with brain metastasis owing to poor efficacy of systemic regimens.
Prognostic value of baseline complete blood count components in advanced gastric cancer patients: A multicenter retrospective study.
Authors: Elsamany Shereef Ahmed , Zeeneldin Ahmed , Tashkandi Emad , Rasmy Ayman Ahamd , Abozeed Waleed , Abdelfatah Gomaa , Bukhari Huda Sharif , Sulaimani Mernan , Firaq Donia Ahmed
Published: May 2020

e16528

Background: Gastric cancer (GC) is one of the most prevalent malignant types in the world and an aggressive disease with a poor 5-year survival. Pretreatment CBC-based biomarkers, including blood neutrophil, lymphocyte, monocyte, and platelet counts; hemoglobin (Hb) levels; and their combinations, such as the neutrophil-lymphocyte ratio(NLR), lymphocyte-monocyte ratio (LMR) and platelet-lymphocyte ratio (PLR), have been reported to reflect systemic and local inflammation associated with cancer progression and prognosis. There has been growing interest in using CBC-based measures as biomarkers for GC. Methods: This chart-review study aimed to evaluate the effect of baseline levels of different components of routine CBC examination as well as other patients and disease characteristics on progression free survival (PFS) and overall survival (OS) in metastatic gastric cancer patients. Total 135 metastatic gastric cancer patients who had diagnosed and treated in three oncology centers in Saudi Arabia from 2011 to 2016 were incorporated. Various potential prognostic factors had measured in univariate and multivariate analysis. Results: After a median follow up of 21.4 months, the median OS / PFS were 11.0 and 6.1 months, respectively. Higher albumin level ( > 3g/dl), low neutrophil percentage ≤ 75%, high lymphocyte percentage > 15%, neutrophil /lymphocyte ≤ 2.5, high eosinophil count > 0.4 k/ml, and EOX/EOF chemotherapy vs. doublet chemotherapy were associated with better PFS in univariate analysis. Conversely, in multivariate analysis, only serum albumin and eosinophil levels were related to PFS. In univariate analysis, higher serum albumin (3 g/dl), low neutrophil percentage ≤ 75%, high lymphocyte percentage > 15%, neutrophil/lymphocyte ≤2.5, high eosinophil count > 0.4 k/ml, receiving 1st line chemotherapy vs. no chemotherapy, receiving > 6 cycles of chemotherapy, receiving EOX/EOF chemotherapy vs. doublet chemotherapy, platelet count ≤450 k/ml, male gender were associated with better OS. In multivariate analysis, lower neutrophil percentage, higher serum albumin, male sex and higher number of chemotherapy cycles were independently associated with OS. Conclusions: Higher eosinophil level was associated with improved PFS while lower neutrophil percentage and higher number of chemotherapy cycles were independent predictors of OS. Higher albumin levels independently predicted better OS and PFS.
The effects of combined modality therapy on stage II-III primary gastric signet ring cell carcinoma.
Authors: Li Yang , Tian Yantao , Zhu Zhikai
Published: May 2020

e16530

Background: To date, there is no well-defined standard of care for gastric signet ring cell carcinoma (GSRC). Clinical guidelines support that combined modality therapy (CMT) on localized gastric cancer, but this may not be appropriate for GSRC as it was generally found to be chemo-resistant. We conducted a population-based study to examine the effects of therapeutic strategies on survival outcomes by using the Surveillance, Epidemiology, and End Results (SEER) data. Methods: Analyses included primary GSRC patients with stage II-III who survived more than 6 months, and were diagnosed between 2006 and 2016 from SEER data.CMT were categorized as gastrectomy group, adjuvant CT group (gastrectomy with adjuvant chemotherapy), neoadjuvant RT group (gastrectomy with neoadjuvant radiotherapy combined adjuvant chemotherapy), and adjuvant CRT group (gastrectomy with chemoradiotherapy). Survival analyses were conducted by Kaplan-Meier method and multivariate Cox proportional hazards models, adjusted for age, gender, race, marital status, histology, AJCC stage, tumor location, and lymph nodes removed. Models were stratified by gender, AJCC stage, lymph nodes removed and tumor location. Results: Of the 1,717 cases of stage II-III primary GSRC, the mean age was 66.9 (SD: 11.0) years, over a half were male (52.8%), and the majority were white (66.0%). A total of 39.9% received adjuvant CRT. The five-year overall survival (OS) rate was 34.6% for this treatment, and 29.6% for adjuvant CT group, 25.4% for adjuvant CRT group, only 23.8% for the gastrectomy group. The median OS of patients treated with adjuvant CRT was significantly longer than that of the gastrectomy group (33 vs 24 months, aHR = 0.71, 95%CI = 0.60,0.84). Although the crude model showed a significant association between adjuvant CT and total survival (cHR = 0.81, 95%CI = 0.68,0.96), the effect measure turned null in the multivariable and sub-group analysis. Independent prognostic factors were adjuvant CRT, ≥60 years old, AJCC stage, and > 20 lymoh nodes removed. Conclusions: In this study, GSRC patients with stage II-III experienced improved overall survival after receiving adjuvant CRT, which provides several treatment implications. Future clinical trials considering adjuvant CRT will be needed to verify the conclusion derived from this study.
The effect of chronic diseases on the clinical effect and survival period of patients with solid tumor treated with UMIPIC.
Authors: Cui Shanshan , Liu Yanping , Wu Yanfei , Shang Wei , Han Wei , Xu Xingyou , Yu Baofa ,   Shandong Baofa Therapeutics, Inc
Published: May 2020

e16532

Background: To observe the effect of chronic disease condition on the therapeutic effect and survival period of cancer patients treated with UMIPIC. Methods: 2594 cancer patients in our hospital from January 2011 to December 2015 who received UMIPIC for the study objects. 576 cases with chronic diseases, 2018 without chronic disease, 840 with lung cancer, 712 with esophageal cancer, 254 with liver cancer, 108 with pancreatic cancer, 93 with gastric cancer, 587 with other cancers. They signed the consent for treatment, evaluated the efficacy, followed up to the clinical effect, adverse reactions, survival data of patients. Results: The side effects of the chronic disease patients with cancer after UMIPIC therapy is fever at 26.56%, pain at 15.10%, the second was hemoglobin reduction 16.48%, leucopenia 5.27%, liver function damage 2.67%, thrombocytopenia 2.45%, nausea 2.26%, vomiting 1.39%, neurotoxicity and hair loss of less than 0.20%, while cancer patients without chronic disease after UMIPIC therapy, side effect is fever at 32.37%, pain at14.87%, hemoglobin reduction 13.26%, leucopenia 6.09%, nausea 2.73%, thrombocytopenia 2.6% 3%, liver function damage 1.77%, vomiting 1.73%, kidney function damage 0.89%, neurotoxicity and hair loss were lower than 0.20%; there is only fever difference in the two groups (P < 0.05).There was no significant difference in other adverse reactions. This may be due to the immunity of normal patients was stronger than that of chronic patients. It was found that the clinical benefit rate of 90.91% in patients with chronic diseases was significantly lower than 93.44% in patients without chronic diseases (P = 0.021); after follow-up, we found that the mean survival time of patients with chronic diseases was 22.149 months, median survival time was 10.300 months, while median survival time of patients without chronic diseases was 22.940 months, median survival time was 11.200 months, and the survival rates of patients without chronic diseases for 1, 2, 3 and 5-year were 48.94%, 29.97%, 25.19%, and 25.18% respectively, it is significantly higher than those of patients with chronic diseases (43.19%, 22.33%, 18.37% and 16.04%) (P<0.05). Conclusions: The survival time and survival rate of the patients without chronic diseases are higher than those of the patients with chronic diseases. The side effects of chronic diseases on the patients with cancer treated with UMIPIC are not significant different except for fever. The patients with chronic diseases can safely receive UMIPIC treatment.
The genomic profile and potential predictive circulating cytokines of gastric cancer combine disseminated intravascular coagulation.
Authors: Xiao Jian , Li Shanshan , Zhai Xiaohui , Liu Xinyi , Chen Yaoxu , Huang Mengli
Published: May 2020

e16543

Background: Advanced gastric cancer (GC) combined with disseminated intravascular coagulation (DIC) is a rare clinical disease, but disease progression was rapid and the prognosis is extremely poor. Therefore, an effective whole-course treatment scheme is urgently needed, and the understanding of the molecular mechanism of the disease is still a blank. Methods: FFPE tissues were collected from 8 DIC and 62 non-DIC Chinese gastric cancers. Whole-exome sequencing (WES) by NGS technology was performed on the tissue samples. We also evaluate the protein level of circulating cytokine among 5 DIC GC and 15 non-DIC GC from the preoperative blood specimens by ELISA detection. Results: More than 700 genes related to cancer were addressed specifically. The most frequent mutated genes in DIC GC group are different from non-DIC GC group. 75% (6/8) DIC GC were detected to harbor AR gene mutations. NCOR2 (50%, 4/8) and KMT2C (37.5%, 3/8) were also most frequent mutated genes. While TP53 (72.6%, 45/62), APC (43.5%, 27/62) and KRAS (38.7%, 24/62) were the most frequent mutated genes in non-DIC gastric cancers. As an exotic comparison, the WES data from the public TCGA-STAD (n = 544) cohort was analyzed. The most frequent mutated genes turned out to be TP53 (45.1%, 205/455), LRP1B (28.6%, 130/455) and ARID1A (24.6%, 112/455). For ELISA detection, protein levels of MIP-1α (p = 0.0311)、IL-8 (p = 0.0435)、TNF-α (p = 0.0339) and MCP-1 (p = 0.0187) were significantly lower in DIC GC group, respectively, as compared to non-DIC GC group. In accordance with result of WES, 60% (12/20) samples in non-DIC GC group had more than one gene variation related to immune activation, while 25% (2/8) samples in DIC GC group had only one gene variation. Conclusions: Our study showed that DIC gastric cancers had unique molecular characteristics. Their development may be driven by malfunction in steroid hormone receptors activation other than TP53. DIC GC harbored less DNA variations than non-DIC GC. Circulating cytokine, such as MIP-1α、IL-8、TNF-α and MCP-1, may be served as potential monitoring indicators in the acute phase of DIC GC patients
Efficacy and safety of camrelizumab combined with FOLFOX as neoadjuvant therapy for patients with resectable locally advanced gastric and gastroesophageal junction adenocarcinoma who received D2 radical gastrectomy.
Authors: Zhao Yuzhou , Han Guangsen , Zhuang Jing , Li Zhimeng , Wang Gangcheng , Li Baodong , Wang Jinbang , Gu Yanhui , Ma Pengfei , Zhang Junli , Cao Yanghui , Liu Chenyu , Li Sen , Zhang Xijie
Published: May 2020

e16549

Background: Neoadjuvant chemotherapy for patients with locally advanced gastric and gastroesophageal junction adenocarcinoma (GC/GEJC) can improve the overall survival without increasing operation risk. Nowadays, immunotherapy has become a new promising neoadjuvant treatment. Therefore, we intended to evaluate the safety and efficacy of camrelizumab (anti-PD-1 antibody) combined with FOLFOX as the neoadjuvant therapy for patients with locally advanced GC/GEJC who received D2 radical gastrectomy. Methods: Patients who were diagnosed as resectable locally advanced GC/GEJC received the neoadjuvant treatment of camrelizumab and FOLFOX every 2 weeks for 4 cycles. Imaging evaluation was performed in 2-4 weeks after neoadjuvant therapy. Patients who had no progression disease (PD) were recruited. Eligible patients underwent gastrectomy with D2 lymph node dissection through laparotomy or laparoscopic surgery. The primary end points were safety and R0 resection rate. Results: From July 24 2019 to January 31 2020, 15 patients were recruited. The mean age was 57 years. A total of 10(67%) were males and 5(33%) were females. According to AJCC 8th, cT3 and cT4 were confirmed in 7(47%) patients and 8(53%) patients, N1 and N2 in 7(47%) patients and 8(53%) patients, respectively. During operation, intraperitoneal metastases were found in 2 patients. Of the 13 surgeries, only 2 were laparoscopic and the others were laparotomy. The surgical procedures included Roux-en-Y (9, 69.2%), Billroth II (1, 7.7%) and jejunum interposition (3, 23.1%). Thirteen patients underwent gastrectomy with D2 lymph node dissection and all of them were confirmed R0 resection by postoperative pathology results. The mean lymph node yield was 44.1±13.2 nodes, positive lymph node yield was 1.8±2.8 nodes. Duration time of surgery was 186.5±45.5 minutes, mean blood loss was 219.2±109 ml during the operation. Mean hospital stays were 13.2±2.4 days. Only 1 patient experienced grade 3 pneumonia. Neither serious intraoperative complications nor immune-related adverse events both prior and post operation were observed. There was no treatment-related death. Conclusions: Camrelizumab combined with FLOFOX as neoadjuvant treatment for patients with locally advanced GC/GEJC showed acceptable toxicity and promising efficacy with low complications and mortality. Clinical trial information: NCT03939962 .
Genomics of esophageal squamous cell carcinoma in African Americans.
Authors: Wadleigh Robert George , Akula Nirmala , Lazerow Susan , Marino Gustavo , Chauhan Suman , Paal Edina , Liu Min-Ling L , Lichy Jack , Erkizan Hayriye Verda
Published: May 2020

e16552

Background: Esophageal cancer (EC) is one of the most lethal cancers with 90% mortality rate. Uneven Worldwide geographical distribution and varying etiologic factors contribute to the heterogenic nature of EC worldwide. In the US, 75% esophageal squamous cell carcinoma (ESCC) is diagnosed in African Americans (AA). However, despite comprehensive and multi-geographical efforts to understand the genomic basis of ESCC, the knowledge of molecular and genetic mechanisms leading to genomic subtyping of AA has been limited due to the underrepresentation of AAs in these studies. We hypothesized that the differences in mutational events in AA ESCC might, in part, cause the disparity in outcome and the mutational events may determine treatment options. Methods: Whole exome sequencing (WES) of matched- tumor and normal-cell DNA from late-stage ESCC of ten AA patients were performed by using Agilent SureSelect XT Human All Exon V6+UTR. Somatic variants per tumor samples called by two or more methods (Mutect2, VarScan2, and Strelka2) were combined and used for downstream population filtering. Somatic copy number changes were determined by using CNVKit in SevenBridges Genomics. Results: Somatic variants called by two or more algorithms filtered and sorted for rare mutations (equal to or less than 1% African originated population frequency) demonstrated an average of 23 nonsynonymous mutations per MB in high mutation rate AA ESCC. The remaining four samples had two or fewer nonsynonymous mutations per MB. TP53 was one of the most frequently mutated gene with 50% of mutation frequency. ARID2 mutated in 30%, EP300 in 20%, and RB1 in 10% of our cohort. Multiple amplified and deleted regions ranging from 94 to 46 were observed in seven samples in contrast to three samples that were silent in terms of copy number variations ranging from 29 to 9. Significant CNV were mostly seen in proliferation, cell cycle and checkpoint genes, squamous cell homeostasis, epithelial to mesenchymal transition, invasion and metastasis, receptor tyrosine kinase and signaling pathways, chromatin remodeling, detoxification, RNA/DNA editing and angiogenesis. Conclusions: WES of ten AA ESCC samples demonstrated a higher mutation rate in a group of patients with many passenger mutations and complex and recurrent copy number changes that affect oncogenic driver genes, which might suggest enhanced subtyping of ESCC in AA.
An analysis of clinicopathological characteristics and prognosis on hepatoid adenocarcinoma of stomach.
Authors: Shi Juan , Chen Yanping , Liu Lin , Su Xiangyu
Published: May 2020

e16558

Background: Hepatoid adenocarcinoma of the stomach(HAS) is a rare type of gastric adenocarcinoma(GAC). At present, histopathology is the gold standard for the diagnosis of HAS, however, HAS is easy to be missed diagnosis, and lack of a perfect diagnosis system and effective treatment strategy. In this research, clinical pathological features will be analyzed to improve the diagnostic system, judge prognosis and provide clues for exploration of pathogenesis and targeted therapy of HAS. Methods: 576 cases including 5 confirmed patients with HAS were enrolled onto this study from 1320 patients with GAC. 10 cases of HAS were diagnosed by the second histopathological examination from the other 571 enrolled cases. 30 cases from the remaining 561 enrolled patients were randomly selected as the control group. The information of the two group cases were completed by collecting the existing case data, detecting the missed immunohistochemical indicators and telephone follow-up. The clinicopathological features of the two group cases were compared, and the treatment and prognosis of 15 HAS cases were analyzed. Results: In this study, 15 cases of HAS were found in 576 patients with GAC, including 5 cases from the 1st pathological diagnosis and 10 cases from the 2nd pathological diagnosis. There was no significant difference in age, gender, HP positive rate, serum CEA or CA19-9 level, tumor size, TNM stage, tumor invasion depth, lymph node invasion, distant metastasis rate, differentiation degree, nerve/vascular invasion, and Ki-67 expression level between the two groups( P> 0.05). Compared with the control group, the serum AFP level, and the expression level of GPC3, AFP, EGFR and VEGF protein of patients in HAS group were significantly high, as well as the patients in the HAS group were more likely to develop liver metastasis( P< 0.05). The mOS was 12 mo vs 42 mo for HAS group vs control group( P< 0.05). Multivariate analysis showed immunohistochemical AFP staining intensity was an independent risk factor for prognosis of HAS. Conclusions: As a special type of GAC, HAS is prone to developing liver metastasis with poor prognosis. Based on the higher missed diagnosis rate of HAS, it is suggested to make 2nd cancer histopathological diagnosis including immunohistochemical detection of AFP and GPC3 for GAC patients with significantly increased serum AFP level. The intensity of immunohistochemical AFP staining is an independent risk factor for the prognosis of patients with HAS. VEGF, EGFR and PD-1 / PDL-1 may be potential therapeutic targets of HAS, which is worth further study.
Clinical outcomes of patients with gastric cancer according to pre and post-neoadjuvant chemotherapy PD-L1 immunohistochemistry (IHC) expression.
Authors: Ribeiro Heber Salvador de Castro , Costa Wilson Luiz da , Begnami Maria Dirlei de Souza , Mello Celso Abdon Lopes , Neotti Tatiane , Diniz Alessandro Landskron , Godoy André Luis , Farias Igor Correa , Melo Torres Silvio , Vaz da Silva Diego Greatti Vaz , Jesus Victor Hugo Fonseca , Riechelmann Rachel Pimenta , Dias-Neto Emmanuel , Coimbra Felipe José Fernández
Published: May 2020

e16569

Background: The incidence, prognostic and predictive impacts of PD-L1 expression in locally advanced gastric cancer is unknown. We aimed to determine the expression of PD-L1 by CPS in the pre-treatment biopsy and surgical specimens of patients (pts) with gastric cancer who received neoadjuvant therapy and its association with pathological response and survival outcomes. Methods: Retrospective cohort of pts treated at a cancer center from 2007 to 2017. Pts with confirmed gastric or GEJ adenocarcinoma who received neoadjuvant treatment and curative-intent D2 surgery were included. Gastric stump tumors and those who had a total esophagectomy were excluded. Clinical data were obtained from medical charts. Biopsy samples and a tissue microarray with the most representative areas of the surgical specimen were used to detect PD-L1 IHC expression with 22C3 phamDx antibody. Results were analyzed using the CPS score. Overall and DFS survival included the Kaplan-Meier product-limit estimator in an ITT analysis and a Cox regression was used to obtain crude and adjusted HR for prognostic factors. Results: 270 pts were included: median age was 58.9 years, most (51.5%) had cT3-T4N+ stages, 45% had diffuse histology and 87.8% completed the preoperative regimen. 13% had a pCR, while 53% had minimal tumor regression. With a median follow-up of 60.3 months (CI 95% 54.7 – 65.8), the median OS and DFS were not reached. 11.4% of biopsies and 18.6% of surgical specimens had positive CPS, with a median score of 3 (IQR 2,0 – 7,5) and 9 (IQR 5.0 – 20.0) respectively. In 18.9% of paired samples the PD-L1 expression was found to be negative in the biopsy sample and positive in the surgical specimen. PD-L1 expression was neither associated with pathologic response after neoadjuvant chemotherapy, nor with survival outcomes. Conclusions: PD-L1 expression on the setting of locally advanced gastric cancer was low and it was different when biopsy and surgical specimens were compared. No impact on survival results could be detected. [Table: see text]
Cardiotoxicity after chemoradiation for locally advanced esophageal cancer: Contributions of substructure and whole heart dose-volume parameters to risk prediction.
Authors: Cai Guoxin , Yu Jinming , Meng Xue
Published: May 2020

e16576

Background: To investigate the predictive value of substructure and whole heart dosimetric parameters for cardiotoxicity and overall survival (OS) in patients with esophageal cancer receiving concurrent chemoradiation (cCRT). Methods: We retrospectively reviewed the records of 125 patients with stage Ⅲ middle and lower thoracic esophageal cancer treated with cCRT from 2011 to 2015. The primary endpoint was grade ≥ 2 cardiac events and the second endpoint was OS. Dose-volume histogram parameters for whole heart, left atrium (LA), left ventricle (LV), right atrium (RA), right ventricle (RV), right coronary artery (RCA), left anterior descending (LAD), left circumflex (LCX), and pericardium were extracted. Automated multivariable logistic regression model selection using the MATLAB-based Dose Response Explorer System was performed. Models were evaluated by Spearman correlation coefficient (Rs) and ROC area. Cox regressions analysis was performed to evaluate the association between covariates and OS. Results: Median follow-up was 32 months. The prescribed dose was 60 Gy. Forty patients (32.0%) developed 44 grade ≥ 2 cardiac events, at a median of 14.5 months to first event. The most frequently observed cardiac events were pericardial effusion or pericarditis (n = 13), arrhythmia (n = 12), acute coronary syndrome (ACS, n = 10), and congestive heart failure (CHF, n = 5). Variables included in the models most frequently selected by bootstrap were age, WHO/International Society of Hypertension (ISH) risk score and mean LA dose (Rs = 0.36, AUC = 0.796, p < 0.001) for all cardiac events; age, WHO/ISH risk score and pericardium volume receiving ≥ 20 Gy (Rs = 0.33, AUC = 0.771, p < 0.001) for pericardial events; age, mean LA dose and RA volume receiving ≥ 5 Gy (Rs = 0.31, AUC = 0.754, p < 0.001) for arrhythmic events; and WHO/ISH risk score, mean LA dose and LCX volume receiving ≥ 30 Gy (Rs = 0.37, AUC = 0.812, p < 0.001) for ACS/CHF events. On multivariable analysis, disease progression, Eastern Cooperative Oncology Group (ECOG) performance status, mean LA dose, and gross tumor volume were significant predictors of OS. Conclusions: Whether for whole cardiac, pericardial, arrhythmic or ischemic events, models including corresponding substructure dose outperformed those with whole heart dose in risk prediction. High cardiac substructure dose was associated with a worse OS.
Envafolimab plus chemotherapy in advanced gastric or gastroesophageal junction (G/GEJ) cancer.
Authors: Yin Xianli , Zhang Yun , Deng Yanhong , Xu Nong , Xu Jianming , Li Lei , Song Xiaotong , Lu Haolan , Gong John , Liu Dongfang
Published: May 2020

e16585

Background: Envafolimab is a novel fusion protein of humanized anti-PD-L1 single domain antibody and human IgG1 Fc, formulated for subcutaneously (SC) injection. This study examined the feasibility of combining envafolimab with chemotherapy in advanced G/GEJ cancer. Methods: This study was a single arm, phase Ⅱ trial in adult subjects with previously untreated advanced G/GEJ cancer. Subjects received 8 cycles (2 weeks each) of envafolimab plus FOLFOX regimen followed by envafolimab and 5-FU until progression or unacceptable toxicity. Envafolimab was administrated SC at 5 mg/kg on day 1 of each cycle; FOLFOX consisted of 80 mg/m2 oxaliplatin, 400 mg/m2 5-FU and 400 mg/m2 leucovorin intravenous infusion on day 1, 2400 mg/m2 5-FU administered with a 48-hour continuous infusion on day 1 and 2. Tumor was assessed every 6 weeks per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1). Primary endpoints were safety and tolerability. Toxicity was graded using CTCAE v5.0. Secondary endpoints included objective response rate (ORR), duration of response (DoR). and progression free survival (PFS). Results: A total of 15 subjects were treated and evaluable for response. ECOG performance status was 1 in 80% of subjects. Majority had gastric cancer (86.7%). At the data cutoff, the minimum follow-up was 6 months. The treatment emergent adverse event (TEAE) occurrence was 100% (all grades) and 73.3% (grades 3-4). The most frequent grade 3-4 TEAE included neutrophil count decreased 46.7%, anemia 20.0%, and platelet disorder 20% (3/15). Confirmed ORR was 60% (unconfirmed ORR: 73.3%). Median DOR was not reached. Median PFS was 6.8 months. Conclusions: Envafolimab plus FOLFOX demonstrated a manageable safety profile with promising clinical efficacy as a first line therapy for advanced G/GEJ cancer. Clinical trial information: CTR20181124 .
Racial disparities in patients with unresectable stage III/IV esophageal cancer at time of diagnosis: A National Cancer Database Analysis.
Authors: Sadaps Meena , Mehta Neal , Zhao Ran , Wei Wei , Bhatt Amit , Khorana Alok A.
Published: May 2020

e16589

Background: Significant racial disparities exist in the patterns of care and clinical outcomes for patients with early stage, non-metastatic esophageal cancer but data in advanced esophageal cancer are lacking. In this study, we aim to evaluate racial disparities in patients with locally advanced/metastatic, unresectable esophageal cancers. Methods: We identified patients in the National Cancer Database with esophageal cancer, from 2004 to 2016, with unresectable stage III/IV disease at time of diagnosis. We compared overall survival (OS) between different racial groups as well as other demographic and socioeconomic factors that may have contributed to this disparity. Secondary factors that were studied included age, sex, education, histology, and location of tumor. Results: 49,139 patients were included in this analysis. Median age was 64.5 years and 39,314 (80.0%) were male. 16,723 (34.0%) patients had stage III disease and 32,416 (66.0%) patients had stage IV disease. 16,208 patients (33.0%) had squamous cell carcinoma and 32,931 (67.0%) had adenocarcinoma. Patients were stratified into one of the following six categories for race: Caucasian (40,139; 81.7%), African American (5,571; 11.3%), Asian (907; 1.8%), Hispanic/Latino (1,793; 3.6%), Native American (145; 0.3%), and other (167; 0.3%). African Americans had worse median OS (Table) than Asians (p = 0.000), Hispanic/Latinos (p = 0.000), and Caucasians (p = 0.001) when analyzed in a pairwise comparison using log-rank testing. Within the African American subset, older age ( > 70 years) (p = 0.00), male gender (p = 0.00), and tumor location in the mid (p = 0.02) or upper third (p = 0.00) of the esophagus were associated with worse outcomes using Cox’s multivariate regression model. Conclusions: Racial disparities persist even in unresectable stage III/IV esophageal cancer patients with African Americans noted to have worse clinical outcomes as compared to most other races including Caucasian, Asian, and Hispanic/Latino patients. Further research is warranted to determine the cause for this disparity and to implement the necessary changes to improve outcomes for these patients. [Table: see text]
Effect of significant incidence of Braf p.V600E mutations in esophageal cancer on potential use of tyrosine kinase inhibitors.
Authors: Moorthy Thurai , Rajasooriyar Chrishanthi , Ginige Anusha , Ranatunge Niluka , Surenthirakumaran Rajendra
Published: May 2020

e16591

Background: Routine diagnosis of esophageal cancer varies from locally advanced to metastatic at presentation. Most of these patients are cachectic at presentation and physically not suitable for radical tri-modality treatment as per the CROSS trial. Hence, the prognosis of esophageal cancer remains guarded. Presently, tyrosine kinase inhibitors (TKI) are successfully used in treating melanoma, non-small cell lung cancer, and a possibility for treating esophageal cancer. Allele Specific Multiplex Sequencing (ASMS) detects somatic mutations in samples with low mutant copies and in the presence of overwhelming wild type. Hence, we have re-evaluated and are reporting the findings of the incidence of Braf p.V600E in esophageal cancer using ASMS. Methods: DNA was extracted from 40 formalin fixed paraffin embedded tumor tissue (FFPE) samples that were collected from patients with squamous-cell carcinoma of the esophagus. The Braf p.V600E/K mutations were analyzed using ASMS. All positive results were confirmed by bi-directional ASMS. The results were correlated with patients’ demographic and pathological data. Results: Overall incidence of Braf p.V600E was 92.5% and was present in all stages (IB, IIB, IIIA, IIIB, IIIc and IV) of esophageal cancer. There was no difference in the incidence of Braf p.V600E between patients who smoke, consume alcohol, chew betel or any combination, and those who do not. There is also no gender difference in the incidence of Braf p.V600E. Conclusions: Braf p.V600E is a pivotal driver mutation in the MAPK pathway. Firstly, the data shows incidence of Braf. p.V600E is higher than what is reported in literature and paves the way for follow up with further studies for possible use of TKI targeted chemotherapies. Secondly, incidence of Braf p.V600E mutations could be independent of known cancer etiology (e.g. smoking, consumption of alcohol, chewing betel).
Real-world experience with Lenvatinib in the management of Hepatocellular Carcinoma: A single-center Indian experience.
Authors: Rauthan Amit , Somashekhar S.P. , Patil Poonam , Zaveri Shabber
Published: May 2020

e16596

Background: Sorafenib has been the standard first line treatment for more than a decade in advanced Hepatocellular carcinoma (HCC) patients. Lenvatinib is a novel oral tyrosine kinase inhibitor which inhibits VEGF receptors 1-3, FGF receptors 1-4, PDGF receptor alpha, RET and KIT, and has activity in multiple cancers. In the recent phase III REFLECT trial, Lenvatinib was non-inferior to Sorafenib in the first line management of advanced HCC. It showed better response rates, improved progression free survival (PFS) with similar overall survival (OS). There is no data of Lenvatinib in Indian patients. Methods: This is a single center, retrospective study, which included patients with metastatic or unresectable HCC who received treatment with Lenvatinib at our center. The endpoints were objective response rate (ORR), PFS and toxicity. Results: 31 patients received Lenvatinib from Dec 2017 to Oct 2019. Patients greater than 60kg received 12mg/day and those less than 60kg received 8mg/day. There were 5 females and 26 males. Median age was 60 years (29-78 years). All patients were BCLC stage C. Child Pugh score was A in 20 patients, B in 9 patients and C in 2 patients. AFP was elevated in 25 (80.6%) patients. 26 patients received Lenvatinib as initial therapy, 3 received it after Sorafenib progression, and 2 received after Sorafenib and Nivolumab progression. 6 patients (19.35%) achieved partial response (PR), 12 (38.7%) had stable disease and 13 (41.9%) had progressive disease by recist criteria. ORR was 19.35% and disease control rate was 58%. 2 patients underwent TACE after achieving PR. The median PFS was 7 months. The common adverse events were hypertension, weight loss, palmar plantar rashes, dysphonia and fatigue. Grade 3 AEs occurred in 8 patients (25.8%). 10 patients (32.2%) required dose reduction due to side effects. Conclusions: Lenvatinib has demonstrated a high response rate and disease control rate in our patients. Achieving a PFS of 7 months is an improvement over our previous Sorafenib experience. Further followup will demonstrate the overall survival. It is well tolerated and most side effects can be managed with patient education. The major advantage has been that in contrast to Sorafenib, only 32.2% patients required dose reduction due to side effects. These results are practice changing and Lenvatinib has become our first line regimen in advanced HCC. Lenvatinib would provide a good backbone to combine immunotherapy as first line treatment in future.