bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contemporary trends and survival outcomes of females with esophageal cancer in the United States.
Authors: Baumrucker Camille , Remer Lindsay , Franceschi Dido , Livingstone Alan S , Macedo Francis Igor 
Published: June 2021

e16100 Background: Esophageal cancer (EC) is historically a male dominant disease. Current evidence on the impact of gender on clinical presentation and survival outcomes of EC is limited by small sample size or single institution series. Methods: Patients with EC (stage I-III) were identified in the NCDB (2004-2016). Clinicopathologic and treatment characteristics of male and female patients were compared using Chi-square analysis. Kaplan-Meier and Cox multivariable regression were used to estimate overall survival (OS). Results: Of 62,893 patients included, most patients were male (77.7%). Adenocarcinoma was the most common subtype (66.7%). Squamous cell carcinoma was more predominant in females (57.1% vs. 26.5%, p<0.001). Females were older (68.5 vs. 66.1 yrs; p<0.001) and more likely African American (AA, 14% vs. 8.1%; p<0.001). Females presented with more local disease (stage I, 19.6% vs. 18.2%; p<0.001) while males presented with more locoregional disease (LRD, stage II/III, 80.4% vs 81.8%, p<0.001). Of those with LRD, females less frequently received chemotherapy (CT, 75.4% vs. 82.9%, p<0.001), radiation therapy (RT, 78.9% vs. 82.6%, p<0.001), and esophagectomy (EG, 28% vs. 40.5%, p<0.001). White females with LRD received less CT (76.2% vs. 83.9%, p<0.001), RT (79.5% vs. 83.3%, p<0.001), and EG (30.6% vs. 43.5%, p<0.001). AA females with LRD received less CT (71.9% vs. 75.2%, p=0.013) and RT (77.4% vs. 80.5%, p=0.013) but had similar rates of EG as AA males (p=0.476). Females had worse OS than males (18.1 vs. 19.7mo, p=0.001; cI: 23.5 vs. 31.9mo, p<0.001; LRD: 17.2 vs 18.3mo, p=0.473). White females had worse OS than white males (18.6 vs. 20.4mo, p<0.001) while AA females had better OS (13.5 vs. 12.6mo, p=0.001). White females who underwent EG had improved OS over white males (47.6 vs 38mo, p<0.001) while AA males and females who underwent EG had similar OS (p=0.473). Female gender, older age, AA race, high comorbidity score and clinical stage, and lack of access to CT, RT, and EG were independent predictors of mortality (Table 1). Conclusions: Females with EC seem to have less access to CT, RT, and EG with worse OS than males. Healthcare policies should focus on increasing access to standard treatments for female patients with EC.[Table: see text]
Liver regeneration after radiotherapy in patients with hepatocellular carcinoma: A simple-to-use model and nomogram.
Authors: Su Ting-Shi , Li Li-Qing , Liang Shi-Xiong 
Published: June 2021

e16115 Background: In the past clinical practice of radiotherapy for liver cancer, liver regeneration (LR) which is beneficial to the prevention or recovery of radiation-induced liver injury, has not received enough attention. In current study, we aimed to build and validate multivariate model for liver regeneration after radiation therapy for hepatocellular carcinoma (HCC) based on data from 2 prospective studies. Methods: Thirty patients treated with preoperative downstaging radiotherapy were prospectively included in the training cohort, and 21 patients treated with postoperative adjuvant radiotherapy were included in the validation cohort. Liver regeneration was defined as an increase of more than 10% of normal liver volume in the areas of the protected hepatic segment or lobe, without Child-Pugh class decreased and tumor progression compared to pre-radiotherapy. Model and nomogram of liver regeneration after radiotherapy were developed and validated. The cut-off points of each optimal predictors were obtained using receiver-operating characteristic analysis. Risk stratification based on the cut-off point was conducted to compare the proportion of patients with liver regeneration between subgroups. Results: After radiotherapy, 12 (40%) cases in the training cohort and 13 (61.9%) cases in the validation cohort experienced liver regeneration. The model and nomogram of liver regeneration based on SVs20 (standard residual liver volume spared from at least 20 Gy) and alanine aminotransferase (ALT) showed good prediction performance (AUC = 0.759) in training cohort and performed well (AUC = 0.808) in the validation cohort. The risk stratification according to the cutoffs of SVs20 with 303.4 mL and ALT with 43 U/L demonstrated clear differentiation in risk of liver regeneration between the training(P = 0.049) and entire cohort (P = 0.032). The proportion of patients with liver regeneration decrease progressively with 88.9% in high-probability group (ALT＜43 U/L and SVs20＜303.4 mL), 60% in high-intermediate probability group (ALT ≥43 U/L and SVs20＜303.4 mL), 43.75% in low-intermediate probability group (ALT＜43 U/L and SVs20≥303.4 mL) and 33% in low- probability group (ALT≥43 U/L and SVs20≥303.4 mL). Conclusions: SVs20 and ALT are optimal predictors for liver regeneration. This simple-to-use nomogram is beneficial to the constraints of normal liver outside the radiotherapy target area and make prognosis-based decision without complex calculations. Clinical trial information: ChiCTR1800015350. [Table: see text]
Sintilimab plus anlotinib as first-line therapy in patients (pts) with advanced hepatocellular carcinoma (aHCC).
Authors: Chen Xiaofeng , Li Wei , Wu Xiaofeng , Zhao Fengjiao , Wang Deqiang , Wu Hao , Gu Yanhong , Li Xiao , Qian Xiaofeng , Hu Jun , Li Changxian , Xia Yongxiang , Rao Jianhua , Yao Aihua , Seesaha Poshita kumari , Shao Qianwen , Dong XiaoWei , Li Xiangcheng , Shu Yongqian 
Published: June 2021

e16146 Background: The synergic combination of anti-PD-1/PD-L1 and antiangiogenic agents has exhibited as an encourage treatment pattern in aHCC. Multi-targeted antiangiogenic TKIs, such as lenvatinib and sorafenib, are approved for 1st-line treatment of aHCC. Sintilimab, a novel selective anti-PD-1 monoclonal antibody, has demonstrated encouraging clinical activities in aHCC. The trial aims to explore the safety and efficacy of sintilimab plus anlotinib (a TKI against angiogenesis) in aHCC. Methods: This is a single-arm phase 2 study. Eligible Pts with aHCC, BCLC stage C or B (not amenable for surgery and chemoembolization), Child-Pugh scores≤7 and ECOG PS ≤ 1 received 1st-line treatment of sintilimab (200mg, iv, D1) plus anlotinib (12mg, po, QD, D1-14) every 3 wks until disease progression or unacceptable toxicity. Primary endpoints were safety and objective response rate (ORR, per RECIST 1.1), and secondary endpoints included disease control rate (DCR), progression free survival (PFS), duration of response (DOR) and overall survival (OS). Results: As of January 15, 2021, 20 pts were enrolled (males 18 ; median age 56 yrs [range 41-70] ; BCLCB/C: 5/15 ; Child-Pugh A/B7: 19/1 ; HBV infection 20). All pts received at least two cycles of treatments with median cycles 7.5 [range 2-22]. Median follow-up was 12 months [range 3-19]. The most common treatment-related adverse events (TRAEs) were grade 1-2 with thrombocytopenia (45.0%), hand-foot syndrome (40.0%), hypertension (35.0%), increased AST (35.0%), ALT (30.0%), decreased neutrophil count (25.0%), leukopenia (25.0%). 8 pts experienced manageable grade 3 TRAEs, and no grade 4/5. 12 pts required dose reduction of anlotinib (9 pts to 10 mg and 3 to 8 mg). No treatment withdraw caused by TRAEs. ORR was 40.0% (8/20) with 1 CR and 7 PR, 11 pts were SD, and DCR was 95.0% (19/20). Median DoR was not reached. 6m-PFS rate was 66.4% (95%CI: 47.7%-92.5%), immature median PFS was 14.65 months (95%CI: 5.06 -not reached) with 8 events. Conclusions: The combination of sintilimab and anlotinib showed promising clinical activities with manageable toxicity for first line treatment of aHCC. Clinical trial information: NCT04052152. Research Sponsor: Innovent Biologics, Inc., Chia-Tai Tianqing Pharmaceutical Group Co Ltd. Clinical trial information: NCT04052152.
177Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) in patients with somatostatin-expressing neuroendocrine tumors: A real-world retrospective review of efficacy and safety from an Australian tertiary cancer Center.
Authors: Nalder Mark , Ladwa Rahul , Raina Anant , Burge Matthew E. , Love Amanda , Pattison David A. , Ramsay Stuart , Wyld David 
Published: June 2021

e16198 Background: There is relatively limited data guiding optimal treatment algorithms for inoperable or metastatic neuroendocrine tumours (NETs). The randomised NETTER 1 study established PRRT as a standard of care in midgut NET. The aim of this study was to retrospectively review the efficacy and safety of patients treated with 177Lu-DOTATATE at Royal Brisbane and Women’s Hospital. Methods: Consecutive patients with unresectable or metastatic NET who received their first 177Lu-DOTATATE therapy between 2010 and 2017 were identified. Paragangliomas were excluded. Response rates, progression free survival (PFS) and overall survival (OS) were assessed via a combination of chart review, post-therapeutic 68Ga DOTATATE PET/CT and multi-disciplinary meeting decisions. Gr3/4 haematological and renal safety data was analysed via chart review. Progression free survival (PFS) and overall survival (OS) were assessed via the Kaplan-Meier method. Results: 123 consecutive patients were included in the analysis (57% male, median age 61). Primary site: 41% gastroenteric, 34% pancreatic, 10% lung, 6% colon/rectum, 9% other. Grade 1 (42%), Grade 2 (31%) Grade 3 (6%), unknown (21%). 76% of patients had previously received somatostatin analogues. 80% received four cycles (with persistent myelosuppression the most common cause of ceasing therapy early). 20% of patients received concurrent chemotherapy (10% capecitabine, 10% capecitabine and temozolomide). For the entire cohort, median follow up was 51 months. Median PFS, 34.2 months (95% CI, 30.3 – 38.17) and median OS, 61 months (95% CI, 54.2– 67.8). There was no significant difference in PFS or OS between small bowel and pancreatic patients. Response rates to PRRT included complete response (n = 4, 3%), stable or responding disease (n = 96, 78%), progressive disease (n = 22, 18%), not assessable (1, 1%). Grade 3 or 4 thrombocytopenia, neutropenia or anaemia occurred in less than 1% of patients. Confirmed acute leukaemia occurred in three patients. One patient had grade 3 renal toxicity secondary to treatment. 26 patients received retreatment with 177Lu-DOTATATE at progression with median time to re-treatment of 35 months. Conclusions: This single centre, retrospective audit confirms the efficacy of 177Lu-DOTATATE in the treatment of unresectable and metastatic NETs. Treatment was associated with low rates of severe haematological or renal adverse events. Our results are comparable to similar published reviews.
Correlation of NFE2L2 mutation with higher tumor mutation burden (TMB), microsatellite instability (MSI) and PD-L1 expression in 3,716 cases of Chinese pan-cancer.
Authors: Wu Bin , Li Aijun , Chen Keji , Chen Lin , Zhang Qin , Duan Qianqian , Xiao Mingzhe , Li Mengmeng 
Published: June 2021

e16211 Background: Nuclear factor E2-related factor-2 (NFE2L2) gene encodes a transcription factor which is a member of basic leucine zipper (bZIP) proteins family. Overexpression of NFE2L2 lead to cell proliferation and promoted tumor metastasis. Previous report indicated that NFE2L2 mutation (NFE2L2-MT) was an independent poor prognostic factor in esophageal squamous cell carcinoma (ESCC). However, the correlation between NFE2L2 mutation and pan-cancer types of TMB, MSI, and PD-L1 expression is unclear. Methods: TMB analysis was performed in 3,716 Chinese pan-cancer patients who underwent NGS sequencing using a 539 gene panel. The TMB calculation included synonymous and nonsynonymous mutations and InDels. MSI analysis was performed in 3,110 patients. MSI-H was defined as above 10% positive of the 195 tested microsatellites sites. The PD-L1 expression analysis was performed in 3,415 patients with immunohistochemistry staining (IHC) by antibody SP263. PD-L1 positive was defined as greater than or equal to 1%. The statistical correlation was investigated using Chi-square analysis. TMB value was compared using Wilcoxon Rank Sum test. We used TCGA public database to verify the result. Results: The mutation frequency of NFE2L2 mutation was 2.66% (99/3716). The TOP 5 cancer types were liver cancer 3.53% (14/397), lung cancer 2.97% (42/1416), colorectal cancer 2.02% (7/347), gastric cancer 1.36% (3/221), soft tissue sarcoma 0.53% (1/189). NFE2L2-MT had a significant correlation with higher TMB (p = 2.2e-16), compared with NFE2L2 wild-type (NFE2L2-WT). Among 3110 samples with MSI status, the MSI-H percentage of NFE2L2-MT and NFE2L2-WT were 8.60% (8/93) and 1.33% (40/3017), respectively (p = 1.29e-7). In 3,415 patients with PD-L1 protein expression information, the PD-L1 positive percentage of NFE2L2-MT and NFE2L2-WT were 51.52% (51/99) and 61.9% (1,268/2,048), respectively. NFE2L2-WT has higher PD-L1 positive percentage than NFE2L2-MT (p = 0.01). NFE2L2-MT was significantly correlated with higher TMB and MSI when we used TCGA data to verify, p<0.0001. However, the survival analysis of 1661 MSKCC immunotherapy cohort showed that the median OS of NFE2L2-MT vs NFE2L2-WT was 21 months vs 18 months (p=0.858), but the difference was not significant. Conclusions: NFE2L2 mutation has a very significant correlation with higher TMB and MSI, but not related to PD-L1 expression. However, whether NFE2L2-MT is related to the efficacy of immunotherapy was still unclear and more clinical data were needed.
Predictors of venous thromboembolic complications in patients with pancreatic cancer.
Authors: Katelnitskaya Oksana V. , Kit Oleg I. , Frantsiyants Elena M. , Gevorkyan Yuriy A. , Kaymakchi Oleg Yu. , Snezhko Aleksandr V. , Soldatkina Natalya V. , Kolesnikov Vladimir E. , Dashkov Andrey V. , Poluektov Sergey I. , Aleksandrovich Maksim K. , Kaymakchi Dmitry O. , Pavlov Vladislav K. , Vereshchak Maksim A. , Savchenko Dmitriy A. , Tolmakh Roman E. 
Published: June 2021

e16220 Background: Patients with pancreatic cancer are at high risk for venous thrombosis. Thrombotic episodes are most often recorded at the tumor diagnosis, surgical treatment and chemotherapy courses, or the disease recurrence. This complication postpones the beginning of treatment of the underlying disease and increases the mortality rate of cancer patients. The purpose of the study was to reveal the relationship between clinical characteristics and disorders of hemostasis indicators in patients with pancreatic cancer, and to identify predictors of venous thrombosis. Methods: 246 patients diagnosed with pancreatic cancer were recruited in 2019. The most common histological tumor type was pancreatic ductal adenocarcinoma (91.9%). The most common tumor site was the head of the pancreas (68.3%). Almost half of the patients were initially diagnosed with stage IV cancer (TanyNanyM1). Surgery was performed in 28% of patients. VTEC incidence during the 12-month follow-up period was 15.4%. Results: Analysis of the clinical characteristics and initial hemostasis parameters in patients with and without venous thrombosis revealed that the risk of thrombosis was higher in patients with larger tumors and the presence of distant metastases. High levels of D-dimers at diagnosis doubled the risk of venous thrombosis during antitumor treatment. Conclusions: The most significant predictors of venous thrombosis in patients with pancreatic cancer are tumor size, stage IV, and initially high levels of D-dimer. The study of hemostasis indicators at the stage of diagnosis of pancreatic cancer (D-dimer) can help to identify patients with a high risk of VTEC, for whom anticoagulant prophylaxis with a low hemorrhagic risk is advisable.
New method of hepatic artery reconstruction after its injury or resection.
Authors: Katelnitskaya Oksana V. , Kit Oleg I. , Gevorkyan Yuriy A. , Snezhko Aleksandr V. , Kaymakchi Oleg Yu. , Kolesnikov Evgeniy N. , Soldatkina Natalya V. , Kolesnikov Vladimir E. , Dashkov Andrey V. , Poluektov Sergey I. , Aleksandrovich Maksim K. , Kaymakchi Dmitry O. , Pavlov Vladislav K. , Vereshchak Maksim A. , Savchenko Dmitriy A. , Tolmakh Roman E. 
Published: June 2021

e16221 Background: Restoration the hepatic arterial blood flow is required in traumatic or iatrogenic damage to the hepatic artery and its branches, as well as in the planned resection of the hepatic artery with subsequent reconstruction. Various ways have been proposed to solve this problem: ligation of the hepatic artery and its branches, which is associated with an extremely high mortality rate, reaching 70%, and the need for extensive liver resections; portal vein arteriolization; transposition of the splenic artery with its severe complications (heart attack, abscess) or hepatic artery replacement sometimes are not available and imply aggressive anticoagulant therapy, which is often challenging after extensive oncological interventions. Prosthetic vascular grafts are associated with a high risk of infection. We propose replacement of the common hepatic artery defect by transposition of the left gastric artery and end-to-end anastomosis between the proximal end of the left gastric artery and the distal end of the hepatic artery. Methods: The proposed method was applied in 7 cancer patients - 4 cases of iatrogenic damage to the common hepatic artery in lymph node dissection of the hepatoduodenal ligament and 3 resection of the common hepatic artery with tumor infiltration. The mean age of patients was 53 years. 2 patients had surgery for gastric cancer, 5 - pancreatic cancer. Results: The vascular reconstruction lasted for 17 minutes. No thrombotic complications of the reconstruction area or liver necrosis in the postoperative period were registered. The main advantages of this method were the absence of synthetic materials or deficit blood supply to neighboring organs, and no need for extensive mobilization of the great vessels in other areas (renal artery, abdominal aorta). Conclusions: The proposed method for reconstruction of the hepatic artery allows performing a simple and adequate restoration of the hepatic arterial blood flow, reduced time of the vascular stage of the surgery and reduced incidence of postoperative complications associated with the vascular stage - reduced time of liver ischemia and reduced risk of thrombosis in the reconstruction area.
Relative dose intensity (RDI) of nab-P in gem+nab-P combination in pancreatic cancer treatment and the prognostic role of baseline NLR.
Authors: Varayathu Hrishi , Kurian Lincil , Murugan Anju , Mathew Hephzibah Sara , Rani Sonia , Thomas Beulah Elsa , Sangi Lalram , Somayaji Shalaka , Mathew Smruthy Ann , Gupta Sunny Kumar , Tripathi Priyank , Mufti Suhail Sayeed , Naik Radheshyam , Ajaikumar Basavalinga Sadasivaiah 
Published: June 2021

e16269 Background: Combination of Gem+Nab-P is considered as a dose intense regimen which exhibits synergistic cytotoxic activity and equally effective in increasing survival as FOLFIRINOX regimen in pancreatic cancer. However, number of patients who tolerates such dose intense regimen is found to be less in Indian population. The importance of maintaining optimum RDI is well-known however a low RDI may reflect a poor tolerability. Therefore, the present study aimed to identify desired relative dose intensity and explore the potential of baseline NLR as a prognostic biomarker. Methods: A retrospective chart review was performed of 26 patients with a median age of 65.5 years who received this drug combination either as first-line or second-line treatment for pancreatic adenocarcinoma at a single institution. Treatment outcome was measured using overall survival and toxicities were classified according to CTCAE guidelines. The thresholds for RDI of Gem and Nab-P, and baseline NLR cut-off for predicting survival was calculated by constructing ROC curves. Results: Median overall survival was 11.5 months. Median RDI of Gem and Nab-P was found to be 79% (30-94) and 71% (39 –114) respectively. We estimated a RDI cut-off of 67% in Nab-P and 68% in Gem and observed a statistically significant favorable outcome in patients who received Nab-P with RDI > 67% ( p-0.021). No significant relationship of Gem RDI with outcome was observed. Median overall survival was found to be higher in patients with a baseline NLR < 2.35, patients on D1, D8, D15 treatment regimen and those who received Nano particle bound paclitaxel. Complete assessment of study subjects are enlisted in the table. Grade 3 neuropathy, fatigue, and hyponatremia were reported in 2, 5 and 4 patients respectively. Grade 2 skin rashes and neuropathy were seen in 3 patients each. Conclusions: Our study concludes that tolerability of Gem+Nab P is a concern and it is expected to exhibit a durable response only if it achieves an optimum RDI of Nab-P. The study indicates varied efficacy in different pharmaceutical preparations of paclitaxel favoring the use of nano-particle formulations. The study also indicates that baseline NLR is an important prognostic biomarker in pancreatic cancer[Table: see text]
Lipid and neutrophil accumulation and active inflammasome in high BMI tumor regions of human pancreatic ductal adenocarcinoma.
Authors: Khattab Ahmed , Patruni Sunita , Garciafigueroa Yesica , Phillips Brett , Engman Carl , Khatoon Nazia , Shankar Karthik , Rizvi Ali , Miller Stacey , Zheng Lei , Giannoukakis Nick , Monga Dulabh K. 
Published: June 2021

e16271 Background: Obesity is an established risk factor for cancer and cancer-related mortality. Adipocytes may act as a “damage” signal resulting in the accumulation of innate immune cells, fueling an inflammatory micro-environment. Among the innate immune cells, tumor-associated neutrophils (TANs) are confirmed to accumulate inside the tumor. As obesity is a significant risk factor for a poorer prognosis in pancreatic ductal adenocarcinoma (PDAC), we hypothesize that obesity-driven adipose fuels the progression of PDAC in a TAN and inflammasome-facilitated manner. This may happen through several mechanisms, including genomic instability of aggressive PDAC clonal populations. Methods: Tissue from resected tumors of PDAC patients (n = 44) with a body-mass index (BMI) > 27 (obese [n = 21]) and BMI < 22 (normal [n = 23]) were incubated with anti-human CD66b antibodies and detected using standard immunofluorescent microscopy techniques. Images were acquired in a Zeiss Axioplan microscope workstation and analyzed by ZEN and Metamorph software. Results: We identified the presence of adipocytes in all tissue sections and CD66b+ neutrophils in all tissue sections of normal BMI patients and in 81% of high BMI patients. There is a significantly greater density of adipocytes in the tumor environment when compared to adjacent normal areas, suggesting that these cells are acting as a damage signal. We have also shown that there are fewer total cells per area in the tumor region, suggesting a disorganization that may allow more adipose tissue to form in these areas of high BMI patients. Our novel data also shows that high BMI results in a significantly higher neutrophil count in tumor specific tissue when compared to patients with a low BMI. These data suggest an association between BMI and inflammasome accumulation in the tumor environment. Conclusions: Our data uniquely shows that CD66b+ neutrophils tend to accumulate inside PDAC in high BMI patients and this is associated with intra-tumoral active inflammasomes. The higher concentrations of these inflammasomes in higher BMI patients may be of mechanistic relevance in understanding how inflammation induces progression of PDAC. A larger cohort of tissues from PDAC obtained from low and high BMI individuals will be needed to test our hypothesis and to begin to decipher the role of obesity on inflammation and PDAC progression.