bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reflex testing for RAS and BRAF mutations in metastatic colorectal cancer: A single Canadian academic oncology center experience.
Authors: Cvetkovic Lena , Said Lauren , Ayoub Jean-Pierre M. , Tehfe Mustapha , Florescu Marie , Nguyen Bich Ngoc , Tran-Thanh Danh , Soucy Geneviève , Letourneau Richard , Loungnarath Rasmy , Aubin Francine 
Published: January 2023

86 Background: Patients with left-sided metastatic colorectal cancer (mCRC) without mutations in RAS or BRAF V600E are eligible to a combination treatment of an anti-EGFR monoclonal antibody in association with chemotherapy. This combination is associated with a survival benefit and is recommended by oncology guidelines as first line therapy for RAS/BRAF wild type left-sided mCRC patients. The CHUM (University of Montreal Hospital Center) has implemented reflex testing of RAS/BRAF mutations for mCRC since October 22nd 2019, and was one of the only hospitals in Canada to do so. With this study, we want to demonstrate that reflex testing of these mutations improves the quality of care received by patients. Methods: In this retrospective study, we reviewed pathological and clinical data of 101 patients with newly diagnosed mCRC that had their pathological diagnosis done at the CHUM. Patients diagnosed between July 1st 2017 and October 21st 2019, before implementation of reflex testing, (“Before reflex testing” group, n = 62 patients) were compared to patients diagnosed between October 22nd 2019 and December 31st 2021 (“After reflex testing” group, n = 39 patients). Results: The average delay between the mCRC biopsy and the result of the RAS/BRAF mutations was reduced to 25 days (CI95% 22.6 – 28.1) in the “After reflex testing” group, compared to 154 days (CI95% 111.2 – 202.5) in the “Before reflex testing” group. Respectively 66% (41/62) of patients in the “Before reflex testing” group and 69% (27/39) of patients in the “After reflex testing” received a systemic treatment. At initiation of systemic therapy, results of RAS/ BRAF mutations were available for 85% (35/41) of patients in the “After reflex testing” group, versus only 17% (7/41) of patients in the “Before reflex testing” group. Among patients eligible for an anti-EGFR monoclonal antibody and who received it, 100% of them (6/6) received it in the first line setting in the “After reflex testing” group, compared to 33% (3/9) in the “Before reflex testing” group. Conclusions: Our study shows that with reflex testing of RAS/ BRAF mutations, oncologists have quicker access to all relevant information to make the best treatment decision for their patients. It allows eligible patients to receive an anti-EGFR therapy in the first line setting, as recommended by oncology guidelines.
Symptom burden over time among early-onset young adult colorectal cancer survivors.
Authors: Cheng Justin , Nadim Bahram , Stal Julia , Cohen-Cutler Sally , Gallagher Phuong , Kaslander Jonathan N , Marin Priscilla , Barzi Afsaneh , Lenz Heinz-Josef , Freyer David R. , Miller Kimberly Ann 
Published: January 2023

88 Background: From 1995-2016, rates of colorectal cancer (CRC) have increased among young adults (YA) under 50 years by 2% annually, despite overall rates of CRC among adults over age 65 decreasing. Unfortunately, this population is disproportionately affected by diagnosis at later stage of disease due to systematic and healthcare factors. Such late diagnoses are associated with higher symptom burden among survivors; however, symptom burden among YA early-onset CRC (EOCRC) survivors is poorly understood. The present study aims to characterize symptom burden among YA EOCRC survivors. Methods: A cross sectional survey was administered online in collaboration with a national organization for YA CRC survivors. Respondents (18-49 years) were EOCRC survivors who were 6-36 months from diagnosis/relapse. Survivors endorsed symptoms they experienced among 23 common CRC late effects. Responses were stratified by symptom duration (6-18 versus 19-36 months) to examine differences in endorsement rates among respondents. Results: Respondents (n=235) were colon (n=86) and rectal (n=149) cancer survivors, primarily male 63%, diagnosed at 32.4 years (SD=6.65), with an average of 5.1 (SD=2.57) symptoms. Overall, the most highly reported symptoms were fatigue, perceived change in appearance after treatment, and nail color changes. Comparisons of 6-18 and 19-36 months-from-diagnosis groups revealed similar symptom endorsement rates, with those 19-36 months from diagnosis endorsing constipation/diarrhea, anal bleeding, and incisional discomfort at higher rates than those 6-18 months from diagnosis. The 6-18 and 19-36 months-from-diagnosis groups carried similar symptom burdens of 4.9 (SD=2.57) and 5.1 (SD=2.58), respectively. Conclusions: YA EOCRC survivors endorse numerous symptoms that may interfere with their daily living and quality of life. Similarities in endorsement between 6-18 month and 19-36-month groups suggest symptoms may become chronic and persist beyond cancer treatment. Fortunately, many symptoms can be mitigated or prevented with proper medical and/or psychosocial intervention, patient education, and resource availability. Providers can leverage these findings in their evaluation of YA EOCRC patients during treatment and follow-up care to ensure the delivery of optimal symptom management. [Table: see text]
One-week versus two-week chemoradiotherapy followed by curative surgery in rectal cancer: Long-term comparative pooled analysis of two prospective multicenter phase II trials.
Authors: Lee Jong Hoon , Sung Soo-Yoon , Kim Sung Hwan 
Published: January 2023

96 Background: The optimal short-course chemotherapeutic regimen for rectal cancer has not been clearly defined until now. KROG 10-01 and KROG 11-02 prospective trials investigated the efficacy and safety of one- and two-week chemoradiotherapy (CRT), respectively. We compare and report long-term outcomes by pooling data from two prospective trials for one- and two-week schedules of preoperative CRT and curative surgery in rectal cancer. Methods: Patients eligible for KROG 10-01 and KROG 11-02 involved those with clinical T3-4N0-2M0 rectal cancers. They received preoperative CRT and total mesorectal excision. Patients in KROG 10-01 received radiation of 25 Gy in 5 fractions during one week with 5-fluorouracil/leucovorin. Patients in KROG 11-02 received radiation of 33 Gy in 10 fractions during two weeks with oral capecitabine. Results: A total of 150 patients consisting of 70 patients from KROG 10-01 and 80 patients from KROG 11-02 were collectively analyzed. With a median follow-up time of 89.2 months, the 5-year overall survival (OS) rate was 86.5% in one-week CRT and 85.3% in two-week CRT ( P = 0.84). The 5-year recurrence-free survival (RFS) rate was 83.5% in one-week CRT and 77.1% in two-week CRT ( P = 0.45). One patient (1.4%) in one-week CRT and eleven patients (13.8%) in two-week CRT exhibited pathologic complete regression (ypT0N0M0) after radiotherapy ( P = 0.01). Downstaging (ypT0-2N0M0) occurred in 20 patients (28.2%) in one-week CRT and 27 patients (33.8%) in two-week CRT ( P = 0.50 ). One-week CRT arm had significantly higher acute hematologic (12.8% vs. 3.8%, P = 0.040) and non-hematologic (38.6% vs. 16.3%, P = 0.002) toxicities than two-week CRT arm. Conclusions: Both one- and two-week schedules of CRT showed favorable survival outcomes after seven years of follow-up. But, two-week course achieved more increased tumor response and decreased acute toxicity rather than one-week course. Clinical trial information: KROG 10-01 is registered at ClinicalTrials.gov (number, NCT01129700 ) and KROG 11-02 is registered at ClinicalTrials.gov (number, NCT01431599 ).
Phase 2 randomized, active-controlled, multicenter trial to assess the safety and efficacy of RRx-001 + irinotecan vs. regorafenib + irinotecan in third/fourth-line colorectal cancer.
Authors: Reid Tony R. , Abrouk Nacer , Oronsky Bryan , Caroen Scott , Fisher George A. 
Published: January 2023

97 Background: RRx-001 is a novel cysteine-targeted alkylating agent that, upon binding, under severe hypoxia, which is primarily present in tumors, releases nitric oxide (NO) and other cytotoxic metabolites. The primary biological activities of this hybrid molecule include macrophage repolarization, CD47 downregulation, and vascular normalization. The purpose of this clinical trial (ROCKET) (NCT02096354) was to compare the safety and efficacy of the combination therapy RRx-001 + irinotecan vs. regorafenib + irinotecan in 3rd/4th line colorectal cancer that previously received treatment with irinotecan. Methods: A total of 34 patients were randomized (24 to RRx-001 + irinotecan (RxI) and 10 to regorafenib + irinotecan (RegI)) and were the basis for the intention-to-treat analysis (ITT, comprising all 34 patients). RRx-001 treatment was administered as an up-to-2-month induction therapy or “primer” followed by irinotecan for patients randomized to the RRx-001 arm (24). The efficacy and safety data are presented for the 34 patients in the ITT efficacy analysis. Therapy consisted of intravenous administration of RRx-001 at 4 mg once weekly for up to 2 months followed by intravenous infusion of irinotecan at 180 mg/m2 on day 1 in a 21-day cycle vs. 160 mg oral regorafenib daily for 3/4 weeks followed at progression, if applicable, by irinotecan 180 mg/m2 on day 1 in a 21-day cycle. Results: Median patient follow-up was approximately 14.5 months (SD 4.5 months). Median overall survival was 8.6 months for RxI and 4.7 months for RegI. Median progression free survival was 6.1 months for RxI vs. 1.7 months for RegI (a statistically significant result, two-sided log-rank test, p = 0.0030). Overall response rate was 20.8% for RxI vs. 0% for RegI. Moreover, the toxicity profile of RxI was substantially improved compared with RegI. Conclusions: The results of this trial demonstrate improved efficacy of RxI compared with RegI in patients with metastatic colorectal cancer after previous treatment with irinotecan, and late-stage clinical development in this indication is planned on the strength of the observed “signal” accompanied by a sufficient safety profile. Clinical trial information: NCT02096354 .
Effect of Tabernero's prognostic subgroups or development of neutropenia on survival outcomes of patients with refractory metastatic colorectal cancer (mCRC) treated with trifluridine/tipiracil plus bevacizumab (TASBEV) in real-world practice.
Authors: Martinez-Lago Nieves P. , Alonso de Castro Beatriz , Reboredo Rendo Cristina , Calleja Teresa , Gómez-Randulfe Rodríguez Martín Igor , Silva Diaz Sofia , Parajó Vázquez Iria , Mateos Salvador Maria , Busto Fernandez Fernando , Grana Suarez Begona , De la camara Juan , Reboredo Lopez Margarita 
Published: January 2023

99 Background: TASBEV, compared with TAS-102, was associated with an improvement in progression-free survival (PFS) with tolerable toxicity in a randomized, open-label phase 2 trial. However, the subgroups of patients who may benefit from long-term TASBEV treatment are unknown. Methods: We conducted a retrospective, observational study of patients (pts) with mCRC refractory or intolerant to standard therapies treated with TAS-102 30-35 mg/m2 twice daily on days 1–5 and 8–12 every 28 days plus BEV 5 mg/kg on days 1 and 15 at University Hospital a Coruña (Spain). Results: We recorded 47 pts treated between July 2019 to June 2022. Median age was 65 years (range 41 – 82 years), 78.7% ECOG PS0-1, 51.1% RASmt, 78.7% of pts had liver and 23.4%, peritoneal metastases; 29.8% time since diagnosis of 1st metastases <18 months and 57.4% poor prognostic Tabernero Subgroup. Previous treatment included 94.3% previous antiVEGF treatment and 74.5% received TAS-102 BEV as 3rd line of treatment. Median of cycles received was 4 (range 1-15 cycles). ORR and DCR were 2.4% and 48.8%, respectively. With a median follow up of 15.7 months, median PFS was 4.3 months (95% CI, 3.4-5.1 months) and median OS was 9.8 months (95% CI, 7.3-12.3 months). Univariate analysis of prognostic factors for progression-free and overall survival are listed in the table. Conclusions: In our series identified that Tabernero's prognostic subgroups or the development of grade 3-4 neutropenia during treatment, among others; identify patients who may benefit from long-term TASBEV treatment. [Table: see text]
Penpulimab plus chemotherapy with or without anlotinib as first-line treatment for patients with advanced esophageal squamous cell carcinoma (ANSWER): A randomized, two-arm, clinical trial in progress.
Authors: Wang Wei , Lin Shuimiao , Wang Rong , Wu Dehua 
Published: January 2023

TPS482 Background: For patients with advanced esophageal squamous cell carcinoma (ESCC), the combination of immune checkpoint inhibitors with chemotherapy has demonstrated synergistic antitumor activity and manageable safety profile. Anti-angiogenic targeted drugs for ESCC patients are still being explored. Penpulimab is a humanized high-affinity IgG1 anti-programmed cell death 1 (PD-1) monoclonal antibody engineered to completely eliminate Fcγ receptor binding and Fc-mediated effector functions that can compromise antitumor activity. Anlotinib, an oral small molecule tyrosine kinases inhibitor, targeting VEGFR 1/2/3, FGFR 1-4, PDGFR α/β and c-kit, have been recommended by the guidelines for advanced ESCC in China because of its good efficacy and tolerance. The purpose of the study was to investigate the efficacy and safety of penpulimab plus chemotherapy with or without anlotinib as first-line treatment for patients with advanced ESCC. Methods: This is a multi-center, two-arm, phase II study which enrolled patients with advanced ESCC. Eligible patients are aged 18-75 years, ECOG performance status 0~1. Approximately 100 patients will be randomly assigned 1:1 to induction with penpulimab (200mg, iv, d1, q3w) plus chemotherapy (TP: cisplatin [60-75mg/m2, iv, d1-d3, q3w] plus paclitaxel [135-175mg/m2, iv, d1, q3w] or albumin-bound paclitaxel [200-260mg/m2, iv, d1, q3w]) for 4-6 cycles followed by consolidation with penpulimab (200mg, iv, d1, q3w) (arm 1) or induction with penpulimab (200mg, iv, d1, q3w) plus anlotinib (10mg/d [<60kg] / 12mg/d [≥60kg], p.o., d1~14, q3w) plus chemotherapy (TP: cisplatin [60-75mg/m2, iv, d1-d3, q3w] plus paclitaxel [135-175mg/m2, iv, d1, q3w] or albumin-bound paclitaxel [200-260mg/m2, iv, d1, q3w]) for 4-6 cycles followed by consolidation with penpulimab (200mg, iv, d1, q3w) and anlotinib (10mg/d [<60kg)/12mg/d [≥60kg], p.o., d1~14, q3w) (arm 2). Randomization will be stratified by gender (male or female), age (<65, >65), PD-L1 combined positive score (CPS; <1, ≥1, ≥5, ≥10), metastatic site, history of surgery and disease. Patients in arm 1 were treated with second-line anlotinib combined with penpulimab after progression until further disease progression. Patients in arm 2 will continue treated with first-line anlotinib combined with penpulimab until disease progression. Tumor imaging assessment will be performed q6w for 1-6 cycle and q9w thereafter. The primary endpoint was objective response rate (per RECIST v1.1 assessed by investigator). Secondary endpoints included disease control rate, progression-free survival (per RECIST v1.1 assessed by investigator), overall survival, safety and quality of life score. Enrollment in this trial is ongoing. Clinical trial information: NCT05214222 .
Perioperative penpulimab plus anlotinib combined with chemotherapy for locally advanced gastric cancer: A single arm, multicenter, phase II clinical trial.
Authors: Wang Mian , Zhou Wei , Miao Yan , Tan Zhaobang , Li Yiding , Hong Liu 
Published: January 2023

TPS485 Background: Perioperative therapy, especially whether preoperative neoadjuvant therapy (NAT) can improve R0 resection rate and prolong overall survival of patients with locally advanced gastric cancer, has been paid more and more attention. NAT is mainly defined as a preoperative chemotherapy or chemoradiotherapy, aiming at increasing radical resection rate by downstaging tumor and eliminating micrometastases. Anlotinib is an oral multi-targeted tyrosine kinase inhibitor targeting VEGFR1/2/3, FGFR1-4 and PDGFRα/β, which effectively blocks tumor neovascularization and growth. Previous phase I/II clinical trials suggested that penpulimab monotherapy as second-line therapy was well tolerated and showed clinical anti-tumor activity in gastric or gastroesophageal junction carcinoma (GC/GEJ) (NCT03352531, NCT04172506). It was demonstrated an objective response rate (ORR) of 26.3%, a disease control rate (DCR) of 42.1% in GC/GEJ patients (pts) using penpulimab monotherapy. This trial was designed to assess the feasibility and efficacy of penpulimab plus anlotinib combined with chemotherapy in perioperative treatment of pts with locally advanced gastric cancer. Methods: This is a multi-center, prospective, single-arm, phase II study. Resectable GC pts with TNM stage T3~4N+M0 per AJCC8th, ECOG PS 0-1, were enrolled and treated with 3 cycles of preoperative penpulimab (200mg, iv, d1, q3w) + anlotinib (12mg, qd, d1-d14, q3w)+ SOX (oxaliplatin 130mg/m2, iv, d1 and S-1 40-60mg, po, bid, d1-14, q3w), and 12 months of postoperative adjuvant therapy formulated by investigators according to the individual situation of the pts. Primary endpoint was pathological complete response (pCR) rate. Secondary endpoints included major pathologic response (MPR) rate, disease free survival (DFS), objective response rate (ORR), R0 resection rate and safety. Based on a two-sided test for one proportion with 5.0% type I error, 80% power to detect an improvement in the rate of pCR from 13% to 29%, there will be 57 pts enrolled considering 10% of pts dropping out. Clinical trial information: NCT05385900 .
A prospective clinical trial to evaluate the performance of a multi-analyte blood test for early detection of hepatocellular carcinoma among at-risk patients with liver cirrhosis: The CLiMB study.
Authors: Roy Dhruvajyoti , Xu Jianfeng , Taggart David J. , Gallant Max A. , Bush Kisha , Reed Octavia , Akhtar Arshia , Yang Ju Dong , Nguyen Mindie , Li Wei , Van Etten Richard A. 
Published: January 2023

TPS617 Background: Hepatocellular carcinoma (HCC) is the leading cause of cancer-related death in patients with cirrhosis in the U.S. HCC surveillance is associated with significant improvements in early tumor detection, receipt of curative therapy and overall survival in patients with cirrhosis. However, current surveillance strategies suffer from poor adherence and suboptimal sensitivity. The multi-analyte HelioLiver test is a novel blood test for the early detection of HCC. The test provides a qualitative result based on a multiparametric algorithm that incorporates information from cell-free DNA (cfDNA) methylation markers, protein tumor markers (AFP, AFP-L3%, DCP) and patient demographic characteristics (sex, and age). Here, we describe the protocol for a prospective, multicenter clinical trial designed to investigate the performance of this multi-analyte blood test in cirrhosis patients at risk for HCC. Methods: The Prospective Clinical Trial to Detect Liver Cancer through Quantification of cfDNA Methylation in Blood Samples (CLiMB) is a longitudinal, multicenter, prospective study with a targeted enrollment of 1,600 participants. The main inclusion and exclusion criteria are described in the table. Within the Initial Surveillance Visit (t=0 months), all enrolled subjects will provide blood specimens for the multi-analyte blood test and undergo conventional ultrasound to examine the liver. Every subject will then undergo diagnostic imaging by multiphasic MRI to determine the clinical truth. The results of diagnostic imaging will be scored by a Liver Reporting and Data System (LI-RADS) score and the number and size of any malignant lesions identified will be recorded. After the Initial Surveillance Visit (t=0 months), subjects with an indeterminant HCC finding by MRI (LI-RADS 3) will be recommended to have up to three Follow-Up Visits (t=6 months, t=12 months, and t=18 months) to attempt to resolve the clinical truth for these subjects. The primary endpoints of the trial are to demonstrate the superiority for sensitivity and non-inferiority for specificity of the multi-analyte blood test over ultrasound for the detection of HCC. The data of all diagnostic imaging by MRI will be saved and uploaded for evaluation by a blinded, centralized team of radiologists, which will be used as the basis of the clinical truth for all subjects. All participants are currently enrolled across the U.S. from over 40 clinical sites. Clinical trial information: NCT03694600 . [Table: see text]
A phase II trial of hyperthermic intraperitoneal chemotherapy combined with tislelizumab and targeted therapy in high-risk hepatocellular carcinoma after R0 resection.
Authors: Liu Sulai , Zhang Zhihua , Song Yinghui , Li Yuhang , Yi Weimin , Jiang Bo , Peng Chuang 
Published: January 2023

TPS635 Background: Hepatocellular carcinoma (HCC) is the predominant form of liver cancer, accounting for 75%–85% of cases, for which surgical resection represents the most effective treatment, with curative potential. However, the high incidence of tumor relapse (50%–70% 5 years after surgery) has hindered improved survival. Furthermore, early recurrence within 2 years after surgery accounts for 70% of relapsed HCC cases, is rarely treatable, and has been associated with poor survival. With the development of novel tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors for advanced HCC, the management of patients has been greatly improved. However, no guidelines for novel systematic therapy to treat high risk of relapse HCC have been established. Targeted therapy combined with immunotherapy as systemic treatment has become a new approach in high risk of relapse HCC. Hyperthermic intraperitoneal chemotherapy (HIPEC), as an adjuvant treatment of abdominal malignant tumors, has achieved unique effects in the treatment of many cancers. The aim of this study was to assess the activity and feasibility of a combination of HIPEC with Tislelizumab and TKIs for the treatment of high risk of relapse HCC. Methods: The single-center, open-label, one-armed, Phase 2 study (NCT05546619) will enroll ~30 adults who meet the diagnostic criteria of high risk of relapse HCC (multiple tumors or satellite lesions; tumor diameter > 5cm; HCC rupture and bleeding; combined with vascular invasion; AFP > 32ng/ml). Patients will receive the following treatments as noted in the table. The primary and secondary endpoints are listed in the table. Tumor response will be evaluated once every 6 weeks for the first 48 weeks of treatment, and once every 12 weeks thereafter according to RECIST v1.1; safety will be assessed through monitoring the incidence and severity of adverse events graded according to CTCAE 5.0, vital signs and clinical laboratory results. Clinical trial information: NCT05546619 . [Table: see text]