bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and feasibility of systemic anticancer therapy in gastrointestinal (GI) cancer patients on hemodialysis (HD): The largest retrospective study.
Authors: Park Jennifer , McGovern Kerri , Ledbetter Leslie , Kaley Kristin , Rodriguez Teresa , Maloney Antonia , Saif Wasif M. 
Published: May 2020

e16139 Background: There is an increasing incidence of malignancies in patients with chronic kidney disease including patients on HD. Minimal reports exist in the literature regarding optimal management of chemotherapy in HD patients. This study investigates the feasibility of chemotherapy for patients with GI malignancies who were on HD. Methods: We collected retrospective data on 37 patients on HD who were treated for a GI malignancy from 2002-2018. Data points collected included demographics, cancer type, treatment regimens, toxicity and treatment outcomes. Results: Of the 37 patients, 28 patients were male and 9 female. Ethnicity consisted of White (25), African American (7), Hispanic (2) and other (4). Diagnoses included colorectal cancer (11), gastric cancer (7), pancreatic cancer (5), carcinoma of unknown primary (3), esophageal cancer (2), gallbladder cancer (2), peritoneal cancer (2), cholangiocarcinoma (2) and others (3). 7 patients received neoadjuvant chemotherapy with 4 undergoing successful resection of tumor. The following chemotherapies were administered post-HD: 5-FU, capecitabine, carboplatin, cisplatin, epirubicin, irinotecan, oxaliplatin and navelbine. Gemcitabine, docetaxel, paclitaxel and etoposide was given prior to HD. Grade > 3 toxicities included anemia, nausea, vomiting and fatigue. Etiology of anemia was partly attributed to renal etiology. Response rate of treatments for HD patients were comparable to that of treatments for patients with normal renal function. 32 patients (86%) completed treatment as planned. Conclusions: Our data constitutes the largest set of patients with GI malignancies who received chemotherapy while on HD. Chemotherapy was feasible and needed a multi-modality approach. Our data calls for larger studies to further investigate pharmacokinetic parameters of cytotoxic drugs in hemodialysis patients to provide strong evidence based guidelines.
Patient-initiated approach to prevent oxaliplatin induced peripheral neuropathy: A social media experiment.
Authors: Cardinas Dana , George Manju , Norton Amber , Gentzel Renee 
Published: May 2020

e16140 Background: Oxaliplatin continues to be the standard of care in the adjuvant and palliative setting in colorectal cancer (CRC). Although effective in CRC treatment, it is associated with a high risk of chemotherapy induced peripheral neuropathy (CIPN), which can debilitate the patient, prevent completion of care, and deteriorate their quality of life. Methods: Colontown is a Facebook-based CRC patient and caregiver support, education and advocacy group. Live Wire, a Colontown neighborhood that was formed in 2018 to help members manage CIPN, consists of over 700 CRC patients. One member of this group applied ice on hands and feet (‘icing’) during oxaliplatin infusion to limit exposure to chemotherapy via cold-induced vasoconstriction. The member was able to prevent CIPN, gaining the attention of the entire group. Results: Subsequently, popularization of icing occurred, as administrators communicated patient experiences and relayed published results on the effect of oral icing to patients. Several Colontown members voluntarily tried it during their chemotherapy, and reported successful outcomes. Live Wire created an “icing protocol” and distributed it to patients, oncologists, and care teams, both in-person and on social media (sm). Conclusions: This real-world example highlights the role of educated patient advocates on sm. Working with these groups directly can provide insights for the medical community on measures patients can do to prevent chemotherapy-associated side effects. The limited publications on icing to prevent CIPN, although promising, have not been enough to make it a recommended standard practice. Meanwhile, voluntary participation using icing for CIPN is growing in Colontown. At this time, Colontown is discussing with oncologists and cancer centers the potential of creating a clinical trial to verify the efficacy icing has during oxaliplatin infusion as a strategy to counter CIPN. Our hope is that this patient-informed icing protocol will be able to guide the design of a clinical trial on icing. Furthermore, with this “experiment”, we hope to illustrate the advantages of serious engagement with a large patient population through the modern use of social media.
A novel XNA-based NGS panel for cancer diagnostics.
Authors: Gan Qiang , Cui Zhen , Tang Simin , Powell Michael Joseph , Zhang Aiguo , Sha Michael Y. 
Published: May 2020

e16142 Background: Identification of genetic variants with low allelic frequency using NGS method is confounded by the complexity of the human genome sequence and by bias and errors that arise during library preparation, sequencing and analysis. To overcome this, we developed a novel NGS approach employing a modified backbone nucleic acid molecule, Xenonucleic Acid (XNA) to enrich the target mutant before the sequencing. XNA enables to efficiently and selectively suppress wild type targeted DNA amplification but amplify targeted mutant alleles. Methods: We developed this XNA-based NGS for detection of mutations in lung and colorectal cancer which includes 8 genes (KRAS, NRAS, EGFR, BRAF, PIK3CA, APC, CTNNB1 and TP53) and 19 hotspots. Results: With as low as 10 ng input DNA, low allelic frequency mutant analysis powered by the XNAs in the library preparation increased the sensitivity of detection dramatically. There were, on average, 32, 24, 25 and 18-fold enrichment in variant allele frequency (VAF) for samples with original 0.10%, 0.25%, 0.50% and 1.25% VAF mutants, respectively. The analytical specificity is about 92% and analytical sensitivity (LOD) can be down to 0.10% VAF with 1000-2000X on Illumina MiSeq. The reproducibility results were obtained for intra-assays, inter-assays and inter-operator assays, and the CVs of detected VAF% were investigated. These 19 actionable mutants were validated by testing cfDNA and FFPE. Preliminary clinical sensitivity for FFPE sample is about 100% for lung cancer and colorectal cancer samples respectively, comparing to without XNA NGS about 85.7% for lung cancer and 70% for colon cancer. For cfDNA sample its clinical sensitivity is about 100% for lung and colon cancer, but without XNA mediated enrichment NGS is only about 70% for lung cancer and undetectable for early colon cancer. Conclusions: The result demonstrated that XNA can selectively block amplification of wild type alleles and leads to enrich of mutants read, and significantly increases the assay sensitivity without the requirement for NGS deeper sequencing.
Phase II expansion cohort in colorectal cancer to evaluate the safety and tolerability of RRx-001 blood mix.
Authors: Fisher George A. , Caroen Scott , Oronsky Bryan , Williams Jeannie , Reid Tony R. 
Published: May 2020

e16144 Background: In a 34 patient randomized Phase 2 trial in 3rd/4th line colorectal cancer called ROCKET (NCT02096354) of RRx-001 + irinotecan versus regorafenib + irinotecan, RRx-001 + irinotecan demonstrated improved overall survival (OS) (8.6 vs 4.7 months) and progression free survival 2 (PFS2) (7.5 vs. 1.7 months) compared to the regorafenib control arm. The main adverse event attributed to RRx-001 treatment, which involved once weekly peripheral or central infusion, was a painful infusion-related superficial phlebitis in 80% of patients. Following the randomized portion of the ROCKET trial, another 18 colorectal patients were enrolled in an expansion cohort to evaluate the safety and tolerability of an RRx-001 “blood mix”, the objective of which was mitigation of the phlebitic complications of direct RRx-001 infusion. Methods: Therapy consisted of intravenous administration of RRx-001 at 4 mg once weekly via blood mix until progression followed by intravenous infusion of irinotecan at 180 mg/m2 on day 1 in a 21-day cycle. Results: The median OS and PFS2 were 6.3 and 5.2 months, respectively, which was similar to that of RRx-001 administered by direct infusion in the randomized part of the trial. No patients experienced phlebitis. The adverse event profile was otherwise unchanged compared with direct IV infusion of RRx-001. Conclusions: The results of this expansion cohort demonstrate similar activity of RRx-001 given by blood mix followed by irinotecan to RRx-001 given by direct IV infusion followed by irinotecan.RRx-001 alleviated the pain that had been observed in the direct IV infusion and therefore allowed for a shorter infusion time without any apparent compromise in activity (based on OS/PFS2 comparability to earlier results). Finally, since phlebitis in theory may progress to deep venous thrombosis or suppurative thrombophlebitis in hypercoagulable and immunosuppressed cancer patients, blood mix RRx-001 is the preferred method of infusion. Clinical trial information: NCT02096354 .
Survival among colorectal cancer patients with a history of previous cancer.
Authors: Pruitt Sandi , Gerber David E. , Zhu Hong , Heitjan Daniel , Maddineni Bhumika , Singal Amit G , Xiong Danyi , Tavakkoli Anna , Halm Ethan , Murphy Caitlin C. 
Published: May 2020

e16146 Background: A growing number of patients with colorectal cancer (CRC) have survived a previous cancer. Although little is known about their prognosis, this population is frequently excluded from clinical trials. We examined the impact of previous cancer on overall and cancer-specific survival in a population-based cohort of patients diagnosed with incident CRC. Methods: We identified patients aged ≥66 years and diagnosed with CRC between 2005-2015 in linked SEER-Medicare data. For patients with and without previous cancer, we estimated overall survival using Cox regression and cause-specific survival using competing risk regression, separately by CRC stage, while adjusting for numerous covariates and competing risk of death from previous cancer, other causes, or the incident CRC. Results: Of 112,769 CRC patients diagnosed with incident CRC, 15,935 (14.1%) had a previous cancer – most commonly prostate (32.9%) or breast (19.4%) cancer, with many 7505 (47.1%) diagnosed ≤5 years of CRC. For all CRC stages except IV in which there was no significant difference in survival, patients with previous cancer had modestly worse overall survival (hazard ratios from fully adjusted models range from 1.11-1.28 across stages; see Table). This survival disadvantage was driven by deaths due to previous cancer and other causes. Notably, most patients with previous cancer had improved CRC-specific survival. Conclusions: CRC patients who have survived a previous cancer have generally worse overall survival but superior CRC-specific survival. This evidence should be considered concurrently with concerns about trial generalizability, low accrual, and heterogeneity of participants when determining exclusion criteria. [Table: see text]
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.