bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of combined treatment of metastatic colorectal cancer inpatients with liver metastases.
Authors: Trandofilov Mikhail , Gridnev Danila , Popov Anatoly , Sizova Anna , Islamova Dina , Makarov Vladislav , Kostirev Semen 
Published: May 2020

e16026 Background: Combined treatment for patients with metastatic colorectal cancer (mCRC) offers better long-term outcomes and chemotherapy can increase the rate of hepatic resectability for patients with initially inoperable disease. Methods: The analysis included 132 patients diagnosed with mCRC having metastases in the liver treated from 2015 to 2020. Of these, 62 (47%) were men and 70 (53%) women. The average age of the patients was 63 years. At the beginning of the treatment, the overall condition of all patients met ECOG 0-1 points. Primary metastatic CRC had 93 (71%) patients. A total of 39 (29%) patients were diagnosed with advanced disease. Localization of the primary tumor in 25 patients (18.9%) was in the right part of the large intestine and 107 (81.1%) in the left part of the colon. At the time of the sample, metastases were detected only in the liver in 73 patients (55.3%). In the remaining 59 (44.7%) other organs were affected besides the liver. Various types of surgical treatment of metastases in the liver received 42 (31.8%) patients. The decision on the choice of chemotherapy was made by the attending physician on the basis of the recommendations of NCCN and RUSSCO, taking into account the molecular genetic characteristics of the tumor. The decision to apply and choose the method of surgical treatment was taken in conjunction with the surgeon. Results: From the general population of patients receiving complex therapy, 2 groups were identified, between which a comparison was made. The first group (group A) was 42 (31.8%) patients who received some surgical treatment of the liver. The second group (group B) included 90 (68.2%) patients, who for some reason or another, did not receive any surgical treatment. The groups are fairly homogeneous in their characteristics. The median overall survival (OS) in group A was 40.1 months, and in group B, 22.3 months. A similar trend continued in subgroup analysis. The calculation of the PFS was complicated by the fact that surgical operations were given at different stages of complex treatment. Three-year survival in group A was approximately 50%, and in group B, 28%. "Five-year" survival (In those patients who were observed from the start of the study for all 5 years) in group A was 15 %, and in group B, 5,5%. Conclusions: The inclusion of modern surgical techniques in the complex therapy of metastatic colorectal cancer, if possible, at any stage, can significantly increase the life expectancy of patients.
An open-label, single-arm, phase I study to assess the safety, efficacy, and biomarker effects of OMT-110 in patients with refractory colorectal cancer.
Authors: Park Soobong , Lee Haejun , Jeong Keun-Yeong , Baek Jeong-Heum , Chang Chong-Hwan 
Published: May 2020

e16027 Background: A metabolism modulatory anticancer durg candidate, OMT-110, has been applied for phase I clinical trial to evaluate the effect of OMT-110 on safety, efficacy, and biomarker in patients with refractory colorectal cancer resistant to standard therapies. FDG PET-CT has been suggested to be a resonable biomarker for a metabolism modulator and tested as a possible biomarker for OMT-110 in the clinical trial. Methods: The study was composed of 4 cohorts with a specified dose of 12.5, 25, 50, and 100 mg, and each cycle consisted of daily subcutaneous injections for 3 consecutive weeks and had a resting period of 1 week. 3 subjects were enrolled in each cohort in a total of 12 patients. FDG-PET/CT was utilized as a biomarker and the SUVmax was evaluated according to European Organisation for Research and Treatment of Cancer (EORTC) criteria. Results: None of the subjects permanently discontinued or reduced the dose of the investigational drug due to dose-limiting toxicity. Serious drug adverse reactions that resulted in permanent discontinuation of investigational drugs were not reported. Biomarker evaluation using FDG-PET/CT revealed that the tumor responses of 9 from total 9 subjects who completed FDG-PET/CT evaluation by Cycle 2 (8 weeks) were stable metabolic disease (SMD) or higher . In particular, four subjects showed a clear tendency for a decrease in glucose transporting and were evaluated by partial metabolic response (PMR). The result was compatible with the response of Chest CT and APCT according to RECIST. Conclusions: In the study, the results of FDG/PET-CT show OMT-110 modulates the cancer-specific metabolism and thus reduces glucose transportation. Based on the study outcome, FDG PET-CT is possibly considered as a biomarker of OMT-110 and further study is warranted.
Efficacy and safety of fruquintinib in the treatment of poor patients with metastatic gastrointestinal cancer.
Authors: Cui Yanzhi , Jiang Da , Zhang Xue , Huang Fang , Fan Shaoshuang , Wang Long , Hou Ran 
Published: May 2020

e16028 Background: To explore the efficacy and safety of fruquintinib in the treatment of poor PS patients with Metastatic colorectal cancer. Methods: The data of patients who were treated with fruquintinib in oncology department of our hospital from December 2018 to Janurary 2020 were analyzed retrospectively. Fruquintinib 5mg/ days, 3 weeks of withdrawal for 1 week, 4 weeks as a course of treatment, until the disease progression, death or voluntary cessation of treatment. When side effects occurred, the corresponding anti-symptomatic treatment can be given, if the drug side effects still intolerable, the drug was reduced to 4mg/ days or stop treatment. The adverse drug reactions were evaluated by CTCAE 4.0. The curative effects were evaluated by RECIST Version 1.1. All patients were followed up once every 28 days until the disease progression, death or voluntary cessation of treatment. Results: A total of 9 patients were included, including 2 patients with right metastatic colon cancer, 3 patients with advanced rectal cancer, the incidence of fruquintinib side effects was 100%, which occurred in the first 2 months of treatmentand was common in grade 1 and 2. The common symptoms were hypertension (100%),hand and foot skin reaction (50%), proteinuria (12.5%), dysphonia (31.4%), etc.Incidence of severe side effects was 12.5%, hypertension. Conclusions: The adverse reactions of fruquintinib often occurred within 2 months of treatment, most of which were grade 1 or 2; the patients can benefit from fruquintinib in physical state and organ function.
Evaluation of prognosis of rectal cancer patients with neoadjuvant chemoradiotherapy by clinical TNM stage: Is it suitable?
Authors: Chen Yue , Zhang Rui , Dong Xinxin , Liu Fang 
Published: May 2020

e16029 Background: In the Union for International Cancer Control /American Joint Committee on Cancer TNM classification system, the prognosis of rectal cancer patients with adjuvant treatment are based on pre-radiotherapy clinical TNM stage. However, the value of this classification system is still debated. Here, we find that neoadjuvant pathologic TNM stage may be better than clinical TNM stage in patients with rectal cancer. Furthermore, we propose a novel risk stratification which may be more accurate in the assessment of prognosis of these patients. Methods: Between 2010 and 2015, 316 patients with rectal cancer who underwent neoadjuvant chemoradiotherapy followed by radical surgery were included for analysis. The clinicopathological factors for developing recurrences that affected prognosis were analyzed. Results: Our findings showed that the pathological complete response group had significantly better overall survival and recurrence-free survival than did the non-pCR group. Clinical N stage was not only an independent factor for developing recurrences but was also a significant prognostic factor in the pCR group, just as neoadjuvant pathologic TNM stage in the non-pCR group. Based on the independent prognostic factors, pCR patients were stratified into two recurrence risk categories: pCR with cN0 stage or pCR with cN+ stage. Non-pCR patients were stratified into three recurrence risk categories: non-pCR with ypTNM I stage, ypTNM II stage or ypTNM III stage, which might offer greater potential for the prognosis of patients with rectal cancer. Conclusions: Neoadjuvant pathologic TNM stage, rather than pre-radiotherapy clinical TNM stage, was an independent factor for developing recurrences in the non-pCR group. Furthermore, a novel risk stratification, which may be more accurate in the assessment of prognosis of rectal cancer patients, was proposed.
Phase I study (PAYLOAD) of RRx-001 + irinotecan in patients with advanced solid malignancies.
Authors: Kim Edward Jae-Hoon , Carter Corey Allan , Reid Tony R. , Caroen Scott , Oronsky Bryan , Abrouk Nacer D , Quinn Mary Flanagan , Poplin Elizabeth 
Published: May 2020

e16031 Background: RRx-001 is a downregulator of CD-47 and SIRP-alpha, which demonstrated a clinically meaningful improvement in OS and PFS vs. regorafenib when dosed sequentially with irinotecan in a 3rd/4th line colorectal cancer randomized trial called ROCKET (NCT02096354). Recently, RRx-001 has been shown to downregulate PD-L1 on circulating tumor cells. This phase 1 trial named PAYLOAD (NCT02801097) was performed to assess the safety and tolerability of the combination of RRx-001 and irinotecan and to determine a recommended phase II dose (RP2D). Methods: Eligible patients (pts) had adequate organ and bone marrow functions and an ECOG of 0-2 and evaluable refractory advanced solid tumors. RRx-001 was administered once per week for 3 weeks and thereafter once every two weeks. RRx-001 was administered as a 10-15 min IV infusion with irinotecan, which began on Week 4 and which was also given every other week, staggered with RRx-001 . Dose escalation followed a standard 3 + 3 design with co-escalation of RRx-001 and irinotecan as follows: 1: Irinotecan 120 mg/m2 + RRx-001, 0.5 mg 2: Irinotecan 120 mg/m2 + RRx-001, 2 mg 3: Irinotecan 120 mg/m2 + RRx-001, 4 mg 4: Irinotecan 150 mg/m2 + RRx-001, 4 mg Radiological imaging was performed every 8 weeks. Results: 12 pts; 1 gallbladder, 1 ampullary carcinoma, 1 cholangiocarcinoma, 5 colon, 1 GE junction, 2 pancreatic and 2 rectal cancers were enrolled from January 2018 to November 2018. 1 and 18 doses (median: 6 doses) of the combination of RRx-001 and irinotecan were received. The median number of prior treatments was 4 (range 1-5). There were 2 Grade 3 events, leukopenia and anemia, judged not related to RRx-001 but related to irinotecan, 1 Grade 4 event, leukopenia, judged not related to RRx-001 but related to irinotecan and 1 Grade 5 event, neutropenic enterocolitis, also judged not related to RRx-001 but related to irinotecan. No dose-limiting toxicities were identified. The median overall survival was ~ 6.5 months. Conclusions: Alternating weekly infusions of 150 mg/m2 of irinotecan and 4 mg of RRx-001 were well tolerated. No Grade 2 or above diarrhea was observed with irinotecan treatment, which suggests that RRx-001 may protect against gastrointestinal (GI) toxicities, since RRx-001 has also demonstrated anti- oral mucositis and anti-diarrheal properties in other studies.This dose level is the recommended phase 2 dose for future trials. Clinical trial information: NCT02801097 .
Toxicity and tolerance profile of ANTI-EGFRS in metastatic colorectal cancer RAS wild type from the east of Algeria.
Authors: Abdelaziz Ammari , Djebnoune Linda , Khater Besma , Benmansour Aicha , Bensalem Assia 
Published: May 2020

e16032 Background: The results of the different studies showed that the use of anti-EGFRs (Epidermal Growth Factor Receptor) in the management of mCRCs, confront the healthcare team to a new toxicity which until then, were unknown before the era of anti EGFRs. knowing that there were no Algerian patients in these studies, reason for us to do this work. Methods: Between October 2015 and October 2018, our work consists of an epidemiological, observational, descriptive, longitudinal prospective study, including all patients with metastatic colorectal cancer RAS wild type, receiving specific medical treatment with anti EGFR (Panitumumab or Cetuximab) from Medical Oncology Department of Didouche Mourad Hospital of Constantine and the Medical Oncology Department of Batna’s Anti Cancer Center, performance status 0-2, and age 18-75 years. We have completed this work whose main objective is to evaluate the toxicity of anti EGFRs in patients with mCRC RAS wild-type from the east of Algeria. Results: 60 patients received an anti EGFR (Panitumumab or Cetuximab), in our study the most common toxicity was folliculitis with an average onset time of 3.36 weeks and a frequency of 83% of grade 2 and 3. Xerosis was observed in 71% of patients. Paronychia was observed in 50% of patients, in addition to the classical toxicities observed with the different chemotherapy regimens used in mCRCs. For secondary objectives, the median progression free survival in our study was 12 months, with a 95% confidence interval [10,787-13,213]. This median progression-free survival is comparable to those reported in the major anti-EGFR trials. Conclusions: Our results suggest that the Algerian patients with metastatic colorectal cancer RAS wild-type have the same profile of toxicity comparing to the results from different international trials studying anti EGFRs.
The role of continuity of systematic treatment and rehabilitation in patients with metastatic colorectal cancer in elderly and senile age.
Authors: Alekseeva Iuliia Vladimirovna , Semiglazova Tatiana , Tkachenko Elena , Kasparov Boris , Brish Nadezhda , Filatova Larisa Valentinovna , Semiglazov Vladislav , Belyaev Aleksey , Klimenko Veronika , Protsenko Svetlana , Teletaeva Gulfiya Midhatovna , Latipova Dilorom H. 
Published: May 2020

e16041 Background: The concomitant pathology, cancer and geriatric status affect the organism of a sick elderly person. In routine clinical practice elderly patients require comprehensive geriatric assessment (CGO). Despite many treatment strategies for elderly patients with metastatic colorectal cancer (mCRC), there are no use of rehabilitation programs and the assessment of their impact on the treatment tolerability and survival. Methods: The study includes patients with newly diagnosed mCRC stage IV, receiving the first line of chemotherapy (FOLFOX). Patients are given CGO before starting chemotherapy and in dynamics.The following scales are used for geriatric examination: Cumulative Illness Rating Scale for Geriatrics (CIRS-G); Activities of Daily Living (ADL); Daily instrumental activity scale (IADL); Mini nutritional assessment (MNA); Clock Drawing Test (CDT); Geriatric depression scale (GDS). Results: At the moment 29 patients are included in the study. According the results of CGO we determined that elderly and middle-aged patients are similar in cognitive, mental, and nutritional status, but they have statistically significant differences on the MMSE scale (P=0,014). In both groups patients have a decrease in IADL and cognitive functions, the presence of depression. Elderly patients (> 60 years old) are more likely to experience chronic pain (P<0.05) and increased blood pressure (P<0.05) (Table). Conclusions: The management tactics of patients with mCRC in elderly age shouldn't be based only on chronological age, ECOG or the Karnovsky index, that don't reflect functional disorders in patients of the older age group. It is necessary to define algorithms for medical rehabilitation in cancer patients of the older age group. A CGO is aimed at developing a medical rehabilitation plan together with an elderly patient and his environment, and an algorithm for supporting his health status during and after specialized treatment. [Table: see text]
Impact of cetuximab sequence on progress-free survival (PFS) and overall survival (OS) in patients with RAS wild-type metastatic colorectal cancer (mCRC): A real-world study.
Authors: Geng Qirong , Cheng Wenxiu , Chen Zhiyu , Zhang Wen , Zhu Xiaodong , Guo Weijian 
Published: May 2020

e16042 Background: Cetuximab provides a clear clinical benefit in the treatment in patients with RAS wild-type mCRC irrespective of treatment line, but the best sequence is still under investigation. Methods: Patients with RAS wild-type mCRC (2011-2019) who received cetuximab therapy were retrospectively analyzed. They were stratified based on the cetuximab treatment sequence, into the 1st, 2nd, 3rd or later-lines groups. The primary objective was to investigate the impact on Cetuximab sequence (2nd vs. 3rd and later-line) in PFS and OS. As for patients received the 3rd or later-line cetuximab with irinotecan therapy after refractory to the prior 1st and 2nd-line combined chemotherapy with fluoropyrimidine, oxaliplatin, and irinotecan, they will get another PFS of 2nd-line chemotherapy (PFSchemo) besides the PFS of 3rd or later-line cetuximab compared with the cetuximab 2nd-line used patients. We combined the PFSchemo to the PFS of 3rd or later-line cetuximab, then compared with PFS of 2nd -line cetuximab to evaluate the primary objective in PFS. As for the OS of primary objective, we calculated it from start of the 2nd-line of treatment. The secondary objective was to compare the efficacy of cetuximab sequence (1st vs. 2nd and later-lines) in OS calculated from start of the 1st-line of treatment. Results: In total, 193 patients were included: 106 in the 1st, 41 in the 2nd, and 46 in the 3rd-line groups. No difference was observed in baseline characteristics as sex,age,site of primary tumour,number of metastatic sites in the three groups. The median PFS of the 2nd-line and 3rd or later-line groups were 7.1 (95% CI 6.39-7.80) and 13.87 months(95% CI 11.44-16.29) respectively. PFS of the 3rd or later-line group was significantly longer than that of the 2nd-line group (hazard ratio[HR], 0.552; 95% CI, 0.349 to 0.871; P = 0.01). Median OS was 17.8 months (95% CI 13.5-22.1) in the 2nd-line and 27.4 months (95% CI 20.69-34.16) in the 3rd or later-line group (HR, 0.597; 95% CI 0.341 to 1.043; P = 0.07) from start of 2nd-line therapy. The median OS was 28.17 months (95% CI 22.11-34.22) in the 1st-line group and 33.10 months (95% CI 26.88-39.31) in the 2nd and later-lines group (HR, 0.724; 95% CI 0.507 to 1.304; P = 0.075) calculated from the 1st-line of therapy. Conclusions: In a real-world cohort we found that later-line especially 3rd or later-line therapy of cetuximab, may be more benefit for patients with RAS wild type mCRC, as 3rd or later-line use of cetuximab give one more line therapy chance.
Dynamics in treatment response and disease progression of metastatic colorectal cancer (mCRC) patients with focus on BRAF status: Analysis of untreated RAS-wildtype mCRC patients receiving FOLFOXIRI either with or without panitumumab in the VOLFI trial (AIO KRK0109).
Authors: Kurreck Annika , Geissler Michael , Martens Uwe Marc , Riera-Knorrenschild Jorge , Greeve Jobst , Florschütz Axel , Wessendorf Swen , Ettrich Thomas Jens , Kanzler Stephan , Dominik Nörenberg , Seidensticker Max , Held Swantje , Buechner-Steudel Petra , Atzpodien Jens , Heinemann Volker , Stintzing Sebastian , Seufferlein Thomas , Tannapfel Andrea , Reinacher Anke , Modest Dominik Paul 
Published: May 2020

e16055 Background: In patients with mCRC, dynamics of response and disease progression may play a critical role in the understanding of long-term outcome. Depth of response (DpR), time to DpR and post-DpR survival represent innovative endpoints to evaluate response and disease dynamics. Methods: We evaluated DpR by central review of computer tomography images (change from baseline to smallest tumor diameter), time to DpR (study randomization to DpR-image), post-DpR progression-free survival (pPFS = DpR image to tumor progression or death), and post-DpR overall survival (pOS = DpR image to death) with special focus on BRAF mutational status in 66 patients. Results: BRAF wildtype (BRAF-WT) compared to BRAF mutant (BRAF-MT) patients had greater DpR (-57.6% vs. -40.8%, p = 0.013) with a comparable time to DpR (BRAF-WT 4.0 (95% CI 3.1-4.4) months vs. BRAF-MT 3.9 months (95% CI 2.5-5.5), p = 0.8852). pPFS was 6.5 (95% CI 4.7-8.4) versus 2.6 (95% CI 1.0-3.9) months in favor of BRAF-WT patients (HR: 0.24 (95% CI 0.11-0.53; p < 0.001). This also transferred into a significant difference in pOS (33.6 (95% CI 30.0-42.1) versus 5.4 (95% CI 4.7-16.1) months, HR: 0.27 (95% CI 0.13- 0.55); p < 0.001). Further data including primary tumor site will be presented at the meeting. Conclusions: BRAF-MT patients treated within the VOLFI-trial derive a less profound response to treatment as compared to BRAF-WT patients. The substantial difference in outcome according to BRAF status is evident after achievement of deepest response with BRAF-MT patients hardly deriving any further disease control beyond DpR. This is reflected by pPFS and pOS. Our observations hint towards aggressive tumor evolution in patients with BRAF-MT-tumors which may already be molecularly detectable at time of DpR. These findings somehow challenge the currently practiced aggressive treatment strategy of FOLFOXIRI-based 1st-line regimens as they may stimulate treatment resistance and suggest that close monitoring of BRAF-MT patients may include the continuous monitoring of clonal evolution.
A precision medicine drug discovery pipeline to identify dual CDK2/9 inhibition as a novel treatment for colorectal cancer.
Authors: Salman Roghani Roham , Sanjari moghaddam Ali , Rupprecht Gabrielle , Altunel Erdem , Kim So Young , McCall Shannon , Thomas Beatrice , Ware Katie , Somarelli Jason , Hsu David S. 
Published: May 2020

e16056 Background: Colorectal cancer (CRC) is the 3rdmost common form of cancer in the US, responsible for over 50,000 death each year. Therapeutic options for advanced colorectal cancer are limited, and there remains an unmet clinical need to identify new therapies to treat this deadly disease. To address this need, we have developed a precision medicine pipeline that integrates high throughput chemical screens with matched patient-derived cell lines and patient-derived xenografts (PDXs) to identify new treatments for CRC. Methods: We used high-throughput chemical screens of 2,100 compounds across five low-passage, patient-derived CRC cell lines. These results were validated using dose-response IC50curves for CDK1, CDK2, CDK9 or CDK1/2/9 inhibitors and by siRNA-mediated knockdown of CDK9 with or without CDK2 inhibition. Cell cycle arrest analysis was performed by flow cytometry and anaphase catastrophe was analyzed by immunofluorescence staining. For in vivo studies, matched PDXs were treated with either CDK2, CDK9 or dual CDK2/9 inhibitors. Results: We identified the CDK inhibitor drug class as among the most effective cytotoxic compounds across all five CRC lines. Further analysis of the CDK inhibitor class revealed that combined targeting of CDK1, 2, and 9 was the most effective, with IC50 in the range of 110 nM to 1.2 μM. We further validated the efficacy of combined CDK2/9 inhibition using siRNA-mediated knockdown of CDK9 in the presence of a CDK2 inhibitor(CVT-313), and showed that CDK9 knockdown acted synergistically with CDK2 inhibition. Dual CDK2/9 inhibition led to significant G2/M cell cycle arrest and anaphase catastrophe. Finally, combined CDK2/9 inhibition in vivo synergistically inhibited PDX tumor growth as compared to single-agent CDK inhibitors. Conclusions: Our precision medicine pipeline revealed CDK2/9 dual inhibition as a combinatorial therapy to treat CRC and can also be used to identify new and novel therapies