bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase IV study to evaluate the safety of fruquintinib in Chinese real-world clinical practice.
Authors: Li Jin , Wang Zhi-Qiang , Zhong Haijun , He Yifu , Zhang Chen , Niu Zuoxing , Yang Shujun , Zhang Tao , Zhu Liangjun , Shu Yongqian , Peng Jianjun , Song Yan , Li Jian , Yuan Ying , Zhang Haibo , Yu Gengsheng , Hua yun-Qi , Xiao Jianjun , Shi Michael , Su Weiguo 
Published: June 2023

e15568 Background: Fruquintinib is a highly selective, potent, oral tyrosine kinase inhibitor of VEGFR-1, -2, and -3, which was approved in China for 3L mCRC patients based on results of FRESCO study (NCT02314819). In addition, FRESCO-2 (NCT04322539) demonstrated a consistent efficacy and safety profile of Fruquintinib in more heavily treated mCRC worldwide patients. This Phase IV study aims to evaluate the safety of Fruquintinib in real-world clinical practice in China. Methods: This is a prospective, multicenter, phase IV study, to evaluate a real-world safety of Fruquintinib in China. Patients who are within the first cycle of Fruquintinib treatment or plan to use Fruquintinib within 1 week can be enrolled into this study. Three visits are scheduled, including the day of consent, 1 month after consent, and 6 months after consent or 30 days after the last dose (whichever occurs first). The primary endpoint is the collected AE. Results: From April 2019 to Feb 2022, a total of 3005 patients from 96 study sites received at least one dose of fruquintinib and were enrolled in the safety analysis set (SS). The median age of the patients was 60, of which 1053 patients (35.0%) were ≥65.In SS, a total of 1923 patients (64.0%) started Fruquintinib at 5 mg/day. The median relative dose intensity was 85.3%; the median exposure time was 2.7months. In SS, 2291 patients (76.2%) reported TEAEs; 1901 patients (63.3%) reported investigator assessed fruquintinib-related TEAEs.718 patients (23.9%) reported ≥Grade3 TEAEs; 418 patients (13.9%) reported investigator assessed fruquintinib-related ≥Grade3 TEAEs. 330 patients (11.0%) reported SAE; 86 patients (2.9%) reported investigator assessed fruquintinib-related SAE. 169 patients (5.6 %) reported TEAEs leading to death;8 patients (0.3%) reported investigator assessed fruquintinib-related TEAEs leading to death. The most frequent fruquintinib-related TEAEs(＞10%）include palmar-plantar erythrodysesthesia syndrome (PPES,19.4%)，hypertension (15.6%) & fatigue (10.1%); the most frequent Fruquintinib-related≥Grade 3 TEAE (≥1%）include hypertension (6.4%) & PPES (2.2%); The most frequent fruquintinib-related TEAE (≥5%) leading to dose modification was PPES (5.4%). Conclusions: The results are consistent with the fruquintinib safety profile observed in existing clinical studies. No new or significant safety signals were identified. Clinical trial information: NCT04005066 .
Chemotherapy and radiofrequency hyperthermia (oncothermia) in the treatment of metastatic colorectal cancer.
Authors: Deniz Gulhan Ipek , Can Ayten , Tansan Sualp 
Published: June 2023

e15569 Background: Colorectal cancer (CRC) is the second leading cause of death in adults. Standard treatment for metastatic disease includes chemotherapy and biological agents. Although more than 50% of patients respond to multi agent chemotherapy, resistance to treatment is a significant problem and more than 85 % of patients die within five years. Radiofrequency hyperthermia (Oncothermia- OT) is a non-invasive treatment modality which utilizes 13 MHz external radiofrequency waves to selectively heat cancer cells to 45 C, contributing to apoptosis, and aggregation of DNA repair enzymes, potentially overcoming resistance and improving chemotherapy efficacy. It has been used alone or in combination with chemotherapy. Since most metastatic CRC patients have disease limited to the abdominal cavity and liver, Oncothermia can be applied with a single electrode covering the entire abdominal cavity, immediately following chemotherapy without additional side effects. Methods: We treated 25 consecutive CRC patients with disease limited to liver and/or abdominal cavity with chemotherapy and biological agents and concomitant weekly OT (Oncotherm-EHY 3010) for one hour to the whole abdomen. Chemotherapy was FOLFIRI in 2, FOLFOX in 6, FOLFIRINOX in 17. Bevacizumab was used with chemotherapy in 22 and cetuximab in 1 patient. Patients were followed by periodic CT/MRI/PET-CT. Treatment duration ranged from 4 to 60 months. Results: No unexpected or grade III-IV toxicity was observed. Complete response was observed in 3 patients, partial response in 21 patients and stable disease in one patient for an objective response rate of 96%. Median follow up is 20.1 months (range 4-82+ months). 16 patients are alive, 3 with no disease and 13 on treatment. 9 patients have died. Conclusions: Although this is a single center retrospective observation, the combination of chemotherapy with Oncothermia appears tolerable and feasible in metastatic CRC. Despite the limitations of this observation, activity of this multi-modality treatment appears promising. Prospective randomized trials are needed to confirm these findings.
Treatment modalities of regorafenib and survival in metastatic colorectal (mCRC) patients: A real-world multicenter retrospective study.
Authors: Qu Wang , Liu Zimin , Zhu Liangjun , Chen Xiaobing , Liu Bo , Zhao Yun-Bo , Yan Hao , Qu Xiujuan , Li Shengmian , Zang Ai-min , Jiang Zhichao , Sun Yongkun , Zhou Ai-Ping 
Published: June 2023

e15571 Background: Regorafenib has been widely used as the later-line treatment for mCRC. This study aimed to describe the treatment modalities, as well as the efficacy and safety of regorafenib in a real-world setting. Methods: We conducted a retrospective study of patients (Pts) with refractory mCRC receiving at least one cycle of regorafenib as the third or higher line treatment from August 2017 to June 2020 in China. Demographic characteristics, treatment modality and survival were collected. The primary endpoint was overall survival. Uni- and multivariate analysis were conducted by Kaplan-Miere analysis and Cox regression model. Results: A total of 768 Pts from 10 centers were screened and 621 Pts were finally enrolled with a median age of 61 (18-84) years. 376 Pts received regorafenib monotherapy and 245 Pts accepted combination therapy. With a median follow-up time of 28.4 months, the median progression-free survival (mPFS) was 4.3 months (95%CI: 3.8-5.2) and the median overall survival (mOS) was 11.6 months (95% CI: 10.5-12.6). The mOS of Pts received regorafenib monotherapy (R, n = 376), regorafenib plus PD-1 inhibitor (R+I, n = 161), regorafenib plus chemotherapy (R+C, n = 53) and regorafenib plus chemotherapy, PD-1 inhibitor (R+C+I, n = 31) were 10.0, 13.2, 13.5 and 19.3 months, respectively (p = 0.0017). While the median PFS were 3.8, 5.4, 4.6 and 4.8 months, respectively (p = 0.4944). In multivariate analysis, treatment with R+I (HR = 0.712, 95%CI 0.521-0.973; p = 0.0330) and ECOG PS (HR = 0.400, 95%CI 0.232-0,690; p = 0.0010) were the only significant factors for superior mOS. Univariate analysis in subgroups demonstrated longer OS as well as PFS in KRAS mutated or antiangiogenesis therapy naïve Pts in R+I group than those in R group. Moreover, there was a tendency of shorter OS in Pts received 80mg as the final tolerated dose in R+I group compared to 160mg, while Pts received 120mg presented comparable survival. The incidence of all grade treatment-related adverse events was higher in R+I (87.9%) vs R (66.3%) group. Conclusions: The combination of regorafenib and PD-1 inhibitor was commonly adopted as the later-line treatment in mCRC patients in real-world practice and seemed to have a prolonged overall survival than regorafenib alone. Further confirmatory studies are warranted. Clinical trial information: NCT04835324 .
The multi-omics signature to predict sensitive to anti-epidermal growth factor receptor therapy in RAS wild-type colorectal cancer liver metastases.
Authors: Chang Wenju , Liu Yu , Zhou Shizhao , Chen Yuan , Zeng Mengsu , Wang Liansheng , Xu Jianmin 
Published: June 2023

e15578 Background: There are nearly half patients with Ras wild-type metastatic colorectal cancer (mCRC) do not response to Anti-EGFR therapy. Identification of patients who are sensitive to anti-EGFR therapy may increase the response rate and reduce the adverse effect. In this study, we aimed to develop and validate a multi-omics deep learning model to predict cetuximab efficacy in RAS wild type mCRC patients. Methods: In this study, we retrospectively analyzed 213 Ras wild type mCRC patients. The training and testing cohorts comprised patients in Arm A (FOLFOX + cetuximab) of the CHINESE study (NCT01564810) and patients in the CHINESE follow-up study (PMID: 30305811). The external and negative validation cohorts were derived from an independent cohort and Arm B (FOLFOX) of the CHINESE study, respectively. Based on the deep learning framework Pytorch, we first built the radiomic and genetic signature. Next, we passed the CT images and gene data into the trained ResNet18 and Random Forest and then we sum the output probabilities of two models with a weight of 3:7 to obtain the classification probability of the fusion model. Results: The signature successfully predict sensitivity to anti-EGFR therapy (The area under the curve (AUC) of the radiomic signature: 0.75; the genetic signature: 0.81; the fusion signature: 0.86) but failed with chemotherapy (The fusion signature: 0.54). In cetuximab-containing sets, the fusion signature outperformed existing biomarkers for detection of treatment sensitivity (OR = 17.9, 95% CI 3.22–154.31, P = 0.003) and was strongly associated with progression free survival (mPFS: 12.0 vs. 15.0 months, HR: 0.44, 95% CI 0.20–0.99, P = 0.047). Conclusions: The multi-omics signature can serve as an intermediate surrogate marker of anti-EGFR treatment sensitivity and survival. The signature outperformed known biomarkers in providing an early prediction of treatment sensitivity and could be used to RAS wild type mCRC treatment decisions.
A phase II clinical trial of prior regimen rechallenge in third- or later-line treatment for patients with metastatic colorectal cancer.
Authors: Wang Chenchen , Guo Weijian , Huang Mingzhu , Li Wenhua 
Published: June 2023

e15583 Background: Current choices of systemic treatment for patients with metastatic colorectal cancer remained limited, with some patients facing drugless conditions after failure of standard treatment. For those who have responded to the front-line treatment, there is a lack of data from prospective studies, on whether reapplication of former regimens in the later line can still bring clinical benefits. We conducted an exploratory study to evaluate the efficacy and safety of prior regimen rechallenge in the third or later-line treatment in patients with metastatic colorectal cancer (mCRC). Methods: This is a single-arm prospective phase II study (ClinicalTrials.gov Identifier: NCT03485027). The key inclusion criteria were:(1) histologically confirmed mCRC; (2) treatment failure to at least two lines of systemic chemotherapy; progression free survival (PFS) of the rechallenged regimen should be at least four months in the prior setting without unrecoverable toxicity; (3) the time interval between the re-applied chemotherapy regimen and its previous administration was at least 6 months. Eligible patients received the reapplication regimens, including XELOX, FOLFOX, FOLFIRI, Irinotecan monotherapy with or without targeted drug, which was formerly used. Evaluation was repeated every 6 weeks and treatment continues until the disease progression or intolerable adverse effects. The primary end point is PFS. The secondary endpoint is overall survival (OS), objective response rate (ORR), disease control rate (DCR) and treatment safety. Results: From Jan 24, 2018 to Dec 24, 2022, a total of 53 patients were recruited, and 51 patients who had received at least one cycle of rechallenged medication were included in this analysis. The median age was 59 (range 36-82) years old. Among these patients, 38 were administrated with the combination of targeted and chemotherapy as the rechallenge regimen (24 with bevacizumab plus chemotherapy and 14 with cetuximab plus chemotherapy), and 13 with chemotherapy alone (7 with oxaliplatin-based chemotherapy and 6 with irinotecan-based chemotherapy). A total of 41 patients had received the efficacy evaluation after treatment. One patient achieved partial response (tumor change from baseline -38.4%), 23 patients with stable disease and 17 patients with progressive disease. The ORR and DCR were 2.4% and 58.5%, respectively. At the last follow-up date on Jan 31, 2023, the median PFS was 4.0 months (95% CI, 2.62–5.38). The data of OS was still immature. Grade 3 or 4 adverse events were reported in 6 patients (11.76%). The detailed grade 3 or 4 adverse events were neutropenia in 4 patients, oxaliplatin related acute anaphylaxis in 2 patients, diarrhea in 2 patients. Conclusions: For the patients with heavily treated mCRC, the re-application of chemotherapy with front-line treatment regimen has shown a decent effectiveness with acceptable safety. Clinical trial information: NCT03485027 .
Efficacy and safety of encorafenib-based regimens in colorectal cancer: A systematic review of clinical trials.
Authors: Aiman Wajeeha , Jumean Samer , Garcia Jose , Asfeen Ummul , Alkhlaifat Osama , Qirem Murad , Rayad Mohammad Nabil , Ahmad Amaar , DaCosta Theodore , Guron Gunwant K. , Shaaban Hamid Salim 
Published: June 2023

e15600 Background: BRAF gene mutation is present in 10% of the world’s 3rd common cancer, i.e., colorectal cancer (CRC). Constitutive activation of the mitogen-activated protein kinase pathway (MAPKP) results from this mutation, abnormal activation of MAPKP, inhibiting apoptosis and enhancing proliferative activity. In this systematic review, we will assess the efficacy of encorafenib (a BRAF inhibitor) based regimens in CRC. Methods: We followed PRISMA guidelines to conduct this systematic review. A literature search was performed on PubMed, Embase, and Clinicaltrials.gov with mesh terms, ‘’Colorectal Neoplasms’’ and “Proto-Oncogene Proteins B-raf” from the inception of data till 01/05/2023. We screened 4572 articles and included 1 randomized clinical trial (RCT, N = 665), and 4 non-randomized trials (nRCTs, N = 175), measuring the efficacy of encorafenib (E) based regimens in BRAF V600-mutated CRC. Results: In 4 clinical trials (N = 840), 246 patients treated with a double regimen and 373 treated with a triple regimen of E. In 2 clinical trials (N = 319), triple therapy of E + C + Binimetinib showed an overall response rate (ORR) of 47.8% and 26% in the untreated metastatic CRC (mCRC) and phase III randomized trial triple regimen arm, respectively. A recent trial on triple therapy of E + C + nivolumab (N) showed an ORR of 45% with overall survival (OS) and progression-free survival (PFS) of 11.4 and 7.3 months, respectively. In 1 randomized trial (N = 665), ORR improved from 2% in the control arm to 26% and 20% in triple and double regimens, respectively, which was mainly partial response (PR) with complete response (CR) of 4-5% in both groups. The OS was 9 and 8.4 months with a hazard ratio (HR) for death vs. control of 0.52; (95% confidence interval [CI], 0.39 to 0.70; P < 0.001) and 0.60; (95% CI, 0.45 to 0.79; P < 0.001) in the triple and dual regimen, respectively. In 1 trial of dose escalation study, alpelisib (A) was added to E + C and the addition of this third drug showed minimal changes in the ORR from 18 to 19%, and PFS improved from 3.7 to 4.2 months. (Table 1). Conclusions: A combination of BRAF inhibitors with anti-EGFR monoclonal antibodies showed a clinically significant increase in antitumor activity in BRAF-mutated mCRC compared to standard therapy. The addition of MEK/PI3K inhibitor as a third drug to E + C also showed some improvement in ORR and PFS. Triple therapy with E + C + N was also effective and tolerated well by the microsatellite stable (MSS) BRAF mutated mCRC population. Randomized trials are needed. [Table: see text]
First clinical study reporting safety and outcomes of high dose oxaliplatin use in PIPAC for colorectal peritoneal carcinomatosis.
Authors: Somashekhar S.P. , Rajgopal Ashwin K. , Rakshit Susmita , Fernandes Aaron marian , Patil Darshan , Kumar Rohit 
Published: June 2023

e15606 Background: PIPAC in inoperable colorectal peritoneal carcinomatosis has showed better oncological outcomes at existing doses of 92mg/m2. However the maximum dose that can be used and its clinical outcomes is not defined yet. Methods: PIPAC was done at dose 120 mg /m2 oxaliplatin which was established from a phase 2 study. The patient demographics, perioperative findings, adverse events, and outcomes were prospectively recorded. Response rate was graded as Peritoneal Regression Grading Score (PRGS). QoL of the patients was studied according to the EORTC QLQ - C30 score. Results: 42 PIPAC administrations were performed in 15 patients. The median hospital stay was 1.5 day (1-3 day). CTCAE grade 3 was observed in 5 patients, for abdominal pain and nausea, grade 3 fatigue in 4 patients. Transient increase in C- reactive protein was seen in 8 patients, haematological, renal and hepatic functions were not impaired in any patients except for mild transient elevation in AST and ALT levels in 7 patients. 12 patients completed 3 cycles of PIPAC. Of the 15 patients, 3 had complete response (PRGS 1) and 8 had major (PRGS 2), 3 had minor response (PRGS 3). There was improvement in functional scale, symptom scale and overall global health status for all patients. Conclusions: PIPAC can be performed safely at dose of oxaliplatin 120mg/m2. There is better objective & pathological response with this dose with no major complications or side effects to the patients. There is also improvement in quality of life. This dose should be new standard of care for further studies.
Characterization of visits to the emergency room by patients with colorectal cancer in the year prior to their diagnosis: A retrospective study.
Authors: Massarweh Amir , Brenner Baruch , Ofer Jonathan 
Published: June 2023

e15609 Background: Colorectal cancer (CRC) is one of the leading causes of cancer death globally, with more than 0.9 million deaths annually. Despite screening programs, many of the CRC patients (pts) are diagnosed at an advanced stage, resulting in an overall 5-year survival rate of only about 60%. Enhancing the detection of CRC in pts referred to the Emergency Room (ER) could potentially improve early detection and survival outcomes. While the prevalence of initial cancer diagnoses obtained through ER admission is documented, the proportion of individuals diagnosed with CRC who visited the ER during the year proceeding their diagnosis remains unknown. This study aimed to examine the percentage of CRC pts treated at Rabin Medical Center (RMC) who visited the ER in the year prior to diagnosis and to characterize these visits. Methods: A retrospective cohort study was conducted to identify pts diagnosed and treated at RMC for histologically confirmed CRC between 2012-2022 and to characterize their ER visits in the year prior to diagnosis. Each visit was recorded by date and the number of months before diagnosis. ER visits initiated for a recent diagnosis of CRC, i.e., occurring one month before diagnosis, were excluded. Demographic and clinical information (age at ER visit, gender, stage at diagnosis, number of visits, and interval between the first visit and diagnosis) was collected and analyzed. Results: Of the 2,240 pts treated for CRC at RMC between 2012-2022, 476 (21.2%) visited an ER, at RMC (13.3%) or elsewhere (7.9%), in the year prior to diagnosis. The median age at the first visit was 72 years (range: 25-96) and 55.7% were males. Pts were diagnosed with localized, locally advanced, and metastatic disease in 134 (45.0%), 70 (23.5%), and 63 (21.1%) cases, respectively, while stage was not yet established in 31 (10.4%). Quantitative and temporal characteristics of the ER visits are presented (Table 1). Pts had on average 1.6 visits (range: 1-11) in the year prior to diagnosis; 113 (37.9%) had 2 or more visits during that year. The median interval between the first ER visit and the CRC diagnosis was 4 months (range: 2-12); an interval of 5 months or longer was observed in 127 (42.6%) pts. Conclusions: To our knowledge, this is the first report on ER visits of CRC pts in the year prior to their diagnosis. The high percentage of pts visiting the ER highlights the importance of developing screening tools at the ER level to improve early detection and survival outcomes. This is further emphasized by prevalence of repeat ER visits and long interval between the first ER visit and the CRC diagnosis in many cases. [Table: see text]
Transcatheter-directed Y-90 radioembolization compared with chemoembolization for the treatment of hepatic metastases from colon cancer.
Authors: Young Peter , Miles Brittany , Dang Brittany , Mackey James David 
Published: June 2023

e15620 Background: Arterially directed embolic therapy has been a mainstay in the management of hepatic malignancy of both primary and metastatic origin. The benefits of transcatheter-directed Yttrium-90 radioembolization (TARE) and chemoembolization (TACE) in conjunction with systemic therapy are well documented, though only TARE is currently recommended for the management of hepatic metastases from colon cancer. We evaluated patients who underwent TARE or TACE to assess survival rates at 2 years post-procedure. Methods: The TriNetX Diamond network was used for this study. TriNetX provides access to anonymized medical record information on more than 213 million patients in 92 large healthcare organizations. Two cohorts of patients were created utilizing International Classification of Disease-10 (ICD-10) codes. All patients were required to have colon cancer (C18), liver metastases (C78.7), and liver-directed treatment (CPT code 37243). One cohort received chemoembolization (CPT 96420) while the other received Yttrium-90 microspheres (CPT 79445). The cohorts were balanced for age, race, gender, and ethnicity, resulting in 336 patients in each arm. They were then evaluated for risk of death at two years. Results: Patients who received Y-90 had a risk ratio for death of 1.23 compared to patients treated with chemoembolization. Figure 1. Conclusions: Patients who underwent TARE were at a significantly higher risk of mortality at 2 years post-procedure compared to those who underwent TACE. As only Y-90 radioembolization is currently recommended under NCCN guidelines for the treatment of hepatic metastatic lesions from colon cancer, we hope to further discussion among specialists to determine whether TACE may provide an alternative treatment option. [Table: see text]