bluuebunny/crossref_metadata_2025_split huggingface dataset:
Potential of 1.3-diethylbenzimidazolium triiodide in experimental therapy for lung cancer.
Authors: Shikhlyarova Alla I. , Trepitaki Lidia K. , Kaplieva Irina V. , Frantsiyants Elena M. , Kharagezov Dmitry A. , Milakin Anton G. , Leyman Igor A. , Stateshny Oleg N. , Volkova Viktoriya L. , Lazutin Yuriy N. 
Published: June 2021

e15094 Background: The practice of thoracic oncology demonstrates that the lungs often become affected by cancer. The antitumor effect of chemoradiation therapy can be poor, and surgical treatment is associated with reduced functionality of the organ and therefore reduced quality of life of patients. Therefore, nonspecific agents are required that combine a pronounced antitumor effect and, at the same time, restore pulmonary tissue. Our purpose was to study the effects of 1,3-diethylbenzimidazolium triiodide in a rat model of lung cancer by morphological analysis of pulmonary tissues. Methods: An experimental model of lung cancer was created in 60 male and female rats by subclavian infusion of sarcoma 45 cell suspension in the saline at a dose of 0.5 ml (2×106). Iodine-containing preparation was administered enterally at 0.4 mg/kg daily for 5 days with a 2-day interval; treatment was started immediately after the intravenous injection of malignant cells, the therapy lasted for 8 weeks. The morphological control of the lungs was performed at decapitation of animals, tissue processing and staining, by light microscopy using the LEICA DM LS2 microscope with magnification of up to x100. Results: Hematogenous introduction of tumor cells into the lung caused hemorrhage, “acute swelling” of the alveoli, microabscesses, distelectasis, colonization of interalveolar septa with tumor cells and the formation of large metastatic foci. Involutive changes in the tumor tissue were noted together with signs of pulmonary regeneration: after 5 weeks of the treatment – pronounced activation of immune cells and occurrence of elastic fibers with reserve tortuosity; after 8 weeks - active proliferation of epithelial elements that form the bronchial-alveolar apparatus, an increase in surfactant activity in hypertrophied alveoli, and a significant strengthening of the elastic and collagen framework of the alveolar walls. Conclusions: Morphological correlates of the experimental effect of 1,3-diethylbenzimidazolium triiodide indicate its strong antitumor properties and potential for improving the recovery capabilities of the structure-forming elements of the lung.
Healthcare utilization and outcomes in HIV versus non-HIV patients with anal cancer: A nationwide analysis.
Authors: Achebe Ikechukwu , Asotibe Jennifer C , Sherazi Syed Ali Amir , Obi Okechukwu , Attar Bashar , Gupta Shweta , Mullane Michael Russell 
Published: June 2021

e15505 Background: Anal cancer (AC) is the most common HPV-associated cancer in men with HIV. Nearly one third of men with anal cancer have HIV with HPV accounting for 88% of cases. Studies have reported mixed outcomes in HIV-Anal Cancer (HIV-AC) compared to non-HIV-AC patients with most studies being small and retrospective. There were no clear explanations for the differences in the outcomes in both groups. We studied HIV-AC patients from a national database and compared the outcomes and healthcare utilization with non-HIV AC cohort. Methods: We identified all adult patients with AC, with and without HIV, between 2016-2018 from the Healthcare Cost Utilization Project (HCUP) National Inpatient Sample (NIS) database. The groups were compared for socio-demographic differences, inpatient mortality, length of stay (LOS) and total hospital charges (THC). Secondary outcomes studied were rate of acute kidney injury (AKI), tumor lysis syndrome (TLS), lower GI Bleed (LGIB), anemia, tumor lysis (TLS), sepsis, septic shock (SS), neutropenia and protein energy malnutrition (PEM). Statistics was performed using the t-test, univariate and multivariate logistic regression using Stata software. Results: A total of 1235 inpatient admissions with HIV-AC and 10,415 with non-HIV-AC were identified. HIV-AC patients were significantly younger (mean age 50.2 vs 63 years, p < 0.0001) with few over 65 years (8% vs 44.2%, p < 0.0001), more men (82.6% vs 30.8%, p < 0.001), more likely African Americans (AA) (47.8% VS 11.2%, p < 0.0001) and significantly more likely to be treated at a teaching hospital (90.7% vs 9.3%, p < 0.0001) compared to non-HIV-AC cohort. HIV-AC patients had significantly lower odds of inpatient mortality (aOR= 0.26, CI = 0.093 – 0.705, p = 0.008) but higher LOS (7.4 vs 6.5 days, p = 0.02) and higher THC ($74,131 vs $60,864, p = 0.005). Rates of sepsis were higher in HIV-AC (OR = 2.11, CI = 1.465 - 3.028, p < 0.0001) compared to non-HIV-AC, but odds of AKI, TLS, LGIB, SS, anemia, neutropenia and PEM were similar. Conclusions: HIV-AC patients are more likely to be younger, AA, men and have significantly lower inpatient mortality compared to non-HIV-AC, despite higher rates of sepsis. HIV-AC patients being younger and overwhelmingly (90%) treated at teaching hospitals may be contributing to the observed lower mortality. However, the HIV-AC cohort was also a high inpatient healthcare utilizer with significantly increased hospital charges amounting to over $16 million over 3 years. The reversal of sex incidence likely reflects the different exposure to HPV in HIV and non-HIV cohorts. Prospective studies are needed to further evaluate outcomes in HIV-AC patients and identify underlying contributors of higher utilization.
Circulation of tumor cells to destroy correlations in immune system of colorectal cancer patients.
Authors: Sitkovskaya Anastasia O. , Zlatnik Elena Yu. , Kit Oleg I. , Novikova Inna A. , Bondarenko Elena S. , Gevorkyan Yuriy A. , Soldatkina Natalya V. , Kolesnikov Vladimir E. , Aleksandrovich Maksim K. , Dashkov Andrey V. , Poluektov Sergey I. , Kaymakchi Dmitry O. , Mirzoyan Ellada A. , Pavlov Vladislav K. , Vereshchak Maksim A. , Katelnitskaya Oksana V. , Savchenko Dmitriy A. , Tolmakh Roman E. 
Published: June 2021

e15508 Background: The most important stages of metastatic cascade are extravasation and invasion of malignant cells and their surviving in blood. The vast majority of circulating tumor cells (CTC) is destroyed by immune cells. The role of immune system which is able to play not only antitumor but also prooncogenic role is manifested both on local and systemic levels. We studied correlations between lymphocyte subsets` content in blood and in tumor of colorectal cancer patients (II, III, IV stages) with and without CTC. Methods: 60 colorectal cancer patients with II (n = 20), III (n = 20) and IV (n = 20) stages underwent surgery without previous chemotherapy. CTC were measured in blood by CellSearchSystem™ (JanssenDiagnostics, LLC), cell-mediated immunity was assessed in blood by flow cytometry (BD Canto II) and in tissue after surgery by immunohistochemistry; some markers of proliferation and epithelial-mesenchimal transition (EMT) in tumor cells (Ki-67, E- and N-cadherins) were also studied. Criteria of CTC-positive and CTC-negative samples were > 3 and ≤3 respectively. Correlative analysis was performed between the data of the patients with and without CTC in each stage, r was counted. Results: In CTC-positive patients with all the stages the number of strong and moderate correlations between system immunologic factors involving CD8+ appeared to be fewer than in CTC-negative ones (7 vs 19). On the contrary, the number of correlations with T regs in CTC-positive was increased: 5 vs 3 in CTC-negative patients. In patients with CTC > 3 fewer correlations were noted between factors of local and systemic immunity than in CTC-negative ones (9 vs 4 in II stage) and total disruption of all the correlations between system immunologic factors and proliferating tumor cells in III and IV stages was established. Some pathologic correlations appeared in CTC-positive patients like moderate direct one between activated T-lymphocytes` amount and Ki-67+ tumor cells. The number of correlations between intratumoral lymphocytes and tumor cells expressing proliferation and EMT markers in CTC-positive patients was decreased in comparison with CTC-negative ones (4 vs 10 in II stage, 1 vs 9 in III, 2 vs 9 in IV stage). Conclusions: The presence of CTC in colorectal cancer patients rather than tumor stage is associated with imbalance of their systemic and local immunologic factors. This provides some evidence that disruption of interactions in the immune system is at least partly due to CTC.
Analysis of LRP1B as a potential biomarker for colorectal cancer immunotherapy.
Authors: Liu Ruiting , Duan Qianqian , Zhang Qin 
Published: June 2021

e15521 Background: Low-density lipoprotein receptor-related protein 1B (LRP1B), a putative tumor suppressor, is one of the most frequently altered gene in cancer. Recently, there are emerging evidences that LRP1B is involved in sensitivity to melanoma and non-small cell lung cancer immunotherapy. Here we explored the relationship between LRP1B mutation and potential effect of immunotherapy for colorectal cancer (CRC) based on multidimensional data. Methods: Next-generation sequencing (NGS) data of CRC patients (n = 536) from TCGA and Chinese clinical dataset (n = 249) was used to evaluate tumor mutational burden (TMB) differences between LRP1B mutation group and wildtype group. TMB was calculated as the total count of nonsynonymous mutations in coding sequence. Neoantigens of CRC samples (n = 214) were obtained from The Cancer Immunome Atlas. In addition, we investigated the association of LRP1B mutation with 30 immune-related genes, which were classified into 3 categories: immune checkpoint, T-effector and interferon-γ gene signature, and T cell receptor. Results: 22.95% (123/536) patients in TCGA harbored LRP1B mutation. In the Chinese cohort, the LRP1B mutation ratio (24.50%, 61/249) was similar to TCGA. The TMB level of LRP1B mutation group in both TCGA and Chinese cohort was significantly higher than wild-type group (P < 0.001). The TNB between two group is also showed a significant difference (P < 0.001) in TCGA. Of the 30 immune-related genes, 27 (90.0%) genes are differentially expressed (P < 0.05) and all 27 differentially expressed genes have higher expression levels in LRBP1-mutated samples in comparison with wild-type ones. Conclusions: LRBP1-mutated CRC patients have a higher TMB, TNB and show higher expression level with immune-related genes. These results indicated that LRP1B mutation may serve as a potential biomarker of ICI benefit in CRC patients. Moreover, further clinical insights and prospective validation studies are warranted.
Associations between age and stage at presentation among black and white colorectal cancer patients.
Authors: Starks Victoria , Mitchell Edith P. 
Published: June 2021

e15542 Background: Blacks have a 25% higher incidence of colorectal cancer compared to their white societal counterparts. Additionally, the overall mortality rate among black colorectal cancer patients is 50% higher than that of whites. It is suggested that the etiology of this disparity may be inadequate screening for colorectal cancer among racial communities. However, little is known about the correlations between age and stage at presentation among black and white colorectal cancer patients at Thomas Jefferson University Hospital (TJUH). Objective: The objective of this study is to explore diagnostic trends that may unveil differences in age and stage at presentation between black and white colorectal cancer patients. Methods: De-identified patient data was obtained from The Oncology Data Services Department (Cancer Registry) of TJUH. The population cohort (n= 529) included newly diagnosed colorectal cancer patients treated at TJUH from 2015-2019 and included information regarding race, sex, age at presentation, stage at presentation, histological code, tumor markers: KRAS, NRAS, BRAF, MS1, treatment received, surgical findings: tumor size, lymph node involvement, presence of distant metastases at first surgery, response to chemotherapy & disease-free survival. The cohort was divided by age (<50, 50-65, >65). Patient age was compared against AJCC stage at presentation. Results: Findings reveal 12.38% of blacks & 14.29% of whites presented before age 50. 36.19% of blacks and 30.19% of whites presented between ages 50-65. 51.43% of blacks & 55.42% of whites presented after age 65. Additionally, the average age at presentation among blacks was 62.71 years vs. 65.71 years among whites. Lastly, the average stage at presentation among blacks was between 2C and 3A while the average stage at diagnosis among whites was between least 2B and 2C. Conclusions: Within this population, similarities exist among age at presentation between black and white patients, however, differences in stage at presentation exist between blacks and whites. Further research is needed explore how these findings inform the poor clinical outcomes seen among black colorectal cancer patients. Future analysis of this cohort will explore trends regarding time to treatment and treatment received after diagnosis, as similar studies have found differences among racial populations.
A cohort study on the molecular mechanism of distinct therapeutic effects and prognosis in Chinese colorectal cancer patients who underwent neoadjuvant or surgical therapies.
Authors: Xu Ye , Mu Tianhao 
Published: June 2021

e15544 Background: Colorectal cancer is one of the most common and lethal types of cancer in the world. However, the molecular mechanism of colorectal cancer and predicting biomarkers for prognosis are still not fully understood. Methods: Here, we investigated a cohort study to explore the genetic alteration of Chinese colorectal cancer patients. Primary tumors and metastatic tumors were collected and performed with whole exome sequencing. Distinct therapeutic effects of patients were recorded and analyzed. Overall survival of patients was also collected. Results: 57 patients with colorectal cancer (CRC) were enrolled in this study. The mutation landscape of primary tumors showed that the TOP 10 most frequently mutated genes were APC, TP53, KRAS, FRG1, SOX9, PIK3CA, MUC12, SMAD4, MUC4, and DNAH9. The main genetic mutation type was missense. Both primary tumors and metastatic tumors shared the feature of mutated TP53, APC, and KRAS. However, the primary tumors harbored higher mutated FMN2, PLXNB2, DSCAM, SSPO, and PCDHA13, while the metastatic tumors harbored RYR2, RAB15, WNK1, MUC16, and HERC2. Moreover, APC mutation showed a better overall survival (p = 0.029). Co-mutation of APC and FRG1 also presented a better overall survival than one-mutation or none-mutation types (p = 0.029). In contrast, ARID3A mutation (p < 0.001), NUDT6 mutation (p < 0.0099), ZNF717 mutation (p = 7e-04). Curative surgery showed better overall survival than palliative surgery (p = 0.042). However, EBV infection showed no significant relation to overall survival (p = 0.89). In addition, patients harboring FRG1 or CEL mutation were more sensitive to chemotherapy (p = 0.01 and p = 0.02 respectively), while TMB was not significantly related to the effects of chemotherapy. Interestingly, somatic mutations, including NEURL4, DLGAP5, EML1, MBD3L1, SETBP1, TMC4, YTHDC1, PLXNB2, ARHGAP8, and CHD2 were found to be significantly related to patients with family histories (p < 0.05). Conclusions: In this study, we investigated the mutation landscape of primary tumors and metastatic tumors of Chinese colorectal cancer patients. Moreover, the associations between prognosis and different factors, including genetic mutations, surgery strategies, TMB, EBV, and family histories were explored, which may help shed light on better clinical treatment for colorectal cancer in the future.
A phase I study of SHR7390 plus camrelizumab in advanced/metastatic colorectal cancer.
Authors: Wei Xiao-li , Zhang Yang , Zhao Hongyun , Wang Zhiqiang , Li Yu-Hong , Wang Feng , Wang Fenghua , Fang Wenfeng , He Ming-ming , Luo Huiyan , Qiu Miaozhen , Zou Ben-Yan , Xie Jie , Jin Chunlei , Xu Rui-hua 
Published: June 2021

e15553 Background: PD-1 antibody monotherapy has shown durable response in colorectal cancer (CRC) patients (pts) with microsatellite instability (MSI) high status, who account for only 10–15% of all CRC pts. Preclinical studies revealed that inhibition of MAPK pathway with MEK inhibitors can increase T-cell infiltration into tumors and therefore might enhance the antitumor activity of immune checkpoint inhibitor. Thus, this study was conducted to evaluate the safety and antitumor activity of SHR7390, a MEK1/2 inhibitor, plus camrelizumab (anti-PD-1) in pts with CRC. Methods: In this single-arm, open-label, phase I study, pts with treatment-refractory advanced or metastatic CRC were enrolled to receive SHR7390 in an accelerated titration scheme at doses of 0.125, 0.25, and 0.5 mg orally qd, plus camrelizumab at a fixed dose of 200 mg IV q2w. Eligible pts were given a single dose of SHR7390, observed for 7–10 days, and then treated continuously with SHR7390 and camrelizumab in 28-day treatment cycles until disease progression, intolerable toxicities, or withdrawal of consent. A recommended dose for expansion was determined based on the safety and tolerability of the dose escalation stage. The primary endpoints were dose limiting toxicity (DLT) and maximum tolerated dose (MTD). This study is registered with ClinicalTrials.gov, number NCT03182673. Results: At data cutoff on May 30, 2020, 22 pts were enrolled. The median follow-up duration was 6 months. Seven pts had received ≥3 lines of prior treatment. MSI status were available in 21 pts (MSS/MSI-L, n = 18; MSI-H, n = 3). There were two pts each in the SHR7390 0.125 and 0.25 mg cohorts, and 0.5 mg cohort was expanded to 18 pts. One DLT (grade 3 rash) was reported in a pt in the 0.5 mg cohort and the MTD was not reached. Grade 3–4 treatment-related adverse events (TRAEs) were rash (n = 4), increased lipase, oedema peripheral, face oedema, and anemia (n = 1 each). One pt reported a grade 5 TRAE (increased intracranial pressure). Five pts (23%) achieved partial response (0.125 and 0.25 mg cohorts, n = 1 each; 0.5 mg cohort, n =3), including one out of three pts with MSS/MSI-L & BRAF mutant tumors (response lasting 13 months), one out of 15 pts with MSS/MSI-L & BRAF wild type tumors (response lasting 8 months), and all three pts with MSI-H tumors (responses lasting 31, 11, and 10 months, respectively). Three pts with MSS/MSI-L achieved stable disease, and the overall disease control rate reached 36%. Conclusions: SHR7390 plus camrelizumab showed a tolerable safety profile. Preliminary clinical activity was reported regardless of BRAF and MSI status, and future studies are warranted to further evaluate these results. Clinical trial information: NCT03182673.
A retrospective analysis of real-world time on treatment and overall survival in patients with metastatic colorectal cancer receiving cetuximab in third line.
Authors: Gathirua-Mwangi Wambui , Yang Tony , Khan Taha , Wu Yixun , Afable Manuel 
Published: June 2021

e15575 Background: Colorectal cancer (CRC) is the 3rd leading cause of cancer-related deaths in the US. Anti-epidermal growth factor receptor agents improve outcomes of patients with metastatic CRC (mCRC) and are used in multiple lines of therapy. However, real-world time on treatment (TOT) and overall survival (OS) of cetuximab in third-line (3L) have not been described. Therefore, we sought to evaluate TOT, OS, and associated factors in a retrospective study. Methods: A total of 617 patients diagnosed with mCRC and received 3L treatment with cetuximab containing regimens regardless of prior therapies were selected from the nationwide Flatiron electronic health record database (January 2013 - August 2020). TOT was defined as the time from initiation of cetuximab in 3L (index date), to the last recorded date of cetuximab administration. End of therapy was defined if the patients progressed to subsequent line of therapy, or had a record of death. OS was calculated from the index date to date of death or censored to last visit date available. The Kaplan-Meier estimates, and stepwise Cox models were adapted to identify and calculate hazard ratios (HR), and 95% confidence intervals (CI) for factors associated with TOT and OS. Results: Majority of patients receiving 3L treatment with cetuximab containing regimens were: treated in the community setting (96%), less than 65 years old (58%), overweight with a median body mass index (BMI) of 26.2 kg/m² and, received FOLFOX regimens in 1L (46%) and FOLFIRI in 2L (47%). The most common cetuximab containing regimens were cetuximab+irinotecan (36%) and cetuximab+FOLFIRI (34%) and cetuximab monotherapy. The median TOT (mTOT) for patients receiving 3L cetuximab containing regimens was 3.48 months (median interquartile range (mIQR) 3.02-4.17). Higher BMI (obese vs. underweight HR = 0.44, 95% CI 0.28-0.68) was associated with a longer mTOT, while having an ECOG score ≥1 was associated with a shorter mTOT (vs. ECOG = 0, HR = 1.37, 95% CI 1.10-1.72). Also, of all cetuximab containing regimens in 3L cetuximab + FOLFIRI (vs. cetuximab monotherapy) was associated with a longer mTOT (4.63 months, mIQR 3.45-5.55). The median OS (mOS) for patients receiving 3L cetuximab containing regimens was 11.99 months (mIQR 10.87-12.94). Similarly, higher BMI (obese vs. underweight HR = 0.25, 95% CI 0.16-0.40) and 3L cetuximab + FOLFIRI (mOS= 14.3 months, mIQR 11.66-16.85) vs. cetuximab monotherapy were associated with a longer mOS. OS did not differ by patients geographic region (South vs Midwest, p-value 0.35). Conclusions: In this real-world retrospective analysis cetuximab + irinotecan and cetuximab + FOLFIRI were the most common 3L cetuximab regimens. The most common treatment regimens in 1L and 2L were FOLFOX and FOLFIRI respectively. Overall, BMI and treatment regimens received in 3L were associated with mTOT and mOS.