bluuebunny/crossref_metadata_2025_split huggingface dataset:
Second-line bevacizumab plus FOLFOX in patients with metastatic colorectal cancer previously treated with adjuvant oxaliplatin-based chemotherapy.
Authors: Chun Sang Hoon , Kim Jung Hoon , Kwag Seung-Jin , Kang Myoung Hee , Park Ji-Ho , Lee Gyeong-Won , Kang Jung Hun 
Published: January 2023

157 Background: There is a rarity of evidence for retreatment with oxaliplatin for metastatic colorectal cancer (mCRC), especially in combination with bevacizumab. This is a retrospective study of second line bevacizumab (Bev) plus FOLFOX (oxaliplatin, 5-fluorouracil, and leucovorin) in patients with metastatic colorectal cancer previously treated with adjuvant oxaliplatin-containing chemotherapy. Methods: Patients with age older than 18 and histologically confirmed metastatic colorectal cancer treated with second line bevacizumab plus FOLFOX in a single institute between 2015 and 2020 were enrolled. History of previous adjuvant chemotherapy regimens in patients with metachronous metastatic colorectal cancer was analyzed. Progression-free survival (PFS) and overall survival (OS) of the second line treatment were calculated using Kaplan-Meier method and compared between patients pretreated with adjuvant oxaliplatin (ReOx) and oxaliplatin-naive patients (control) with the log rank test. Results: A total of 72 patients were included. 23 patients (ReOx) were pretreated with adjuvant oxaliplatin and 49 patients (control) were oxaliplatin-naive before the second line treatment. There was a tendency of younger age in the ReOx group, but not statistically significant. Liver metastasis was significantly more frequent in the control group. The median PFS and OS in the ReOx group and the control group were 4.3 months (95% confidence interval [CI], 3.67–21.50) versus 5.5 months (95% CI, 4.23–8.20, hazard ratio [HR] = 0.84), and 10.5 months (95% CI, 5.40–30.37) versus 9.4 months (95% CI, 6.00–14.9, HR = 1.01) respectively. There was no significant difference of PFS ( p= 0.523) and OS ( p= 0.9745) between two groups. Conclusions: This study suggests a potential survival benefit of bevacizumab plus FOLFOX for mCRC patients previously treated with adjuvant oxaliplatin-containing treatment comparable to oxaliplatin-naive patients. [Table: see text]
Clinical characteristics and survival trends of patients with metastatic colorectal cancer (mCRC) and peritoneal carcinomatosis who receive metastases surgery in a Spanish cohort.
Authors: Bringas Marianela , Soto Javier , Gutiérrez Alonso Natalia , Muñoz Martín Andrés J. , Calvo Ferrándiz Aitana , Torres Pérez-Solero Gabriela , Ortega Laura , Martín Lozano Rocío , Jiménez Rodríguez Roberto , Gonzalez Caraballo Irene , Gutierrez Ortiz de la Tabla Ana , López Jiménez Carlos , Juliao Caamaño David Salomon , Gómez María Palma , de Lucas Mónica Benavente , Muñoz Marc Ariant Cañete , Alva Bianchi Manuel , Martínez Delfrade Íñigo , Martin Miguel , Garcia-Alfonso Pilar 
Published: January 2023

159 Background: Peritoneal metastases in patients with mCRC are commonly associated with poor outcomes. Some of these patients are candidates to undergo metastases surgery, which may result in better prognosis; however, clinical and molecular characteristics of these patients remain uncertain. Methods: We conducted a retrospective analysis of 166 patients with mCRC and peritoneal metastases in a tumor registry from 2015 to 2021, analyzing the clinical and molecular characteristics, as well as progression-free survival (PFS) and overall survival (OS) of patients who received peritoneal surgery versus those who did not. Results: From the whole population, 65 patients (39%) underwent peritoneal metastases surgery, and several characteristics were more frequent in this subgroup: ECOG 0 (n = 26, OR 2.75, p = 0,0069), age &lt;65 years (n = 43, OR 2.29, p = 0,0162), absence of hepatic metastases (n = 56, OR 3.31, p = 0,0037), single metastatic location (n = 43, OR 3.48, p = 0,0002), normal CEA levels at diagnosis (n = 33, OR 2.02, p = 0,0455) and BRAF mutation (n = 12, OR 3.32, p = 0,0345). Moreover, these patients received more lines of systemic treatment (2.8 vs 2, p = 0,006) and more metastases surgeries (1.7 vs 0.9, p = 0,000). Significant differences in tumor mutational status regardless of BRAF (KRAS, NRAS, MSI, PI3K and HER2), sex and primary tumor location between groups were not found. PFS was longer in patients receiving metastases surgery (median, 13.68 vs 7.76 months; HR for progression 0.64; 95 % confidence interval (CI) 0.46 to 0.89; p = 0,009), as well as overall survival (median NR vs 29.53; HR for death 0.39; 95 % CI, 0.25 to 0.60; p = 0,000). Conclusions: In our cohort, patients with mCRC and peritoneal carcinomatosis who underwent metastases surgery had more frequently less than 65 years, ECOG 0, absence of liver metastases, single metastatic location, normal CEA levels at diagnosis and BRAF mutation. Moreover, this subgroup showed better outcomes with a statistically significant increase in PFS and OS.
Effectiveness of biologic agents among Hispanics in the US with metastatic colorectal cancer.
Authors: Patel Riya Jayesh , Negassa Abdissa , Tolu Seda , Acuna Villaorduna Ana , Goel Sanjay 
Published: January 2023

16 Background: Randomized clinical trials have demonstrated the survival benefit provided by the addition of biologic drugs to chemotherapy (biochemotherapy) in patients with metastatic colorectal cancer (mCRC). However, Hispanic patients are underrepresented in trial populations with limited data on treatment efficacy in them. We aim to compare effectiveness of chemotherapy vs biochemotherapy among Hispanic population in the US with mCRC. Methods: This study includes two cohorts of patients: 1. age ≥ 65 years mCRC diagnosed from 2004 to 2011 who had received at least 1 dose of chemotherapy and had complete Medicare claims data using the Surveillance, Epidemiology, and End Result (SEER)–Medicare linked database, and 2. local Hispanic population from two hospitals in Bronx, New York, from 2006- 2020. Patient data were classified according to whether they received chemotherapy (oxaliplatin, irinotecan, and 5-fluorouracil or capecitabine) or biochemotherapy (bevacizumab, cetuximab, panitumumab, ramucirumab, or aflibercept, started within 3 months of chemotherapy). Overall survival (OS) was defined as the time from starting chemotherapy to death or last follow-up. A weighted Cox regression model was used to assess differences in survival. Results: A total of 188 patients with mCRC were identified. Fifty three (28.2%) received chemotherapy and 135 (71.8%) received biochemotherapy. Median ages were 69 and 68 years, respectively. There were no differences based on median income, marital status, primary site or sidedness, tumor differentiation grades or Charlson Comorbidity Score between both groups. Among patients who received only chemotherapy, 9% received second or greater lines of chemotherapy when compared to 51% in the biochemotherapy group (p <0.001). The median overall survival was 6.6 (95% CI:5.7 - 15.0) months (mo) and 15.9 (12.0 -24.5) mo, respectively. Biochemotherapy conferred an OS benefit with average HR=0.62 (0.41-0.94; p=0.023). This was most evident in the first year (HR=0.53, 0.31-0.89; 0.016), less so in 2nd year (HR=0.65, 0.28 - 1.49; 0.307) and there was an apparent reversal effect beyond 2 years (HR=1.79, 0.41-7.77; 0.436). Conclusions: In this comparative effectiveness study of a cohort of Medicare recipients and the Bronx population, with mCRC, biochemotherapy was associated with an improvement in OS, especially in the 1st year. Patients receiving biochemotherapy are more likely to receive further lines of chemotherapy upon disease progression.
Phase Ib of pembrolizumab (pem) in combination with stereotactic body radiotherapy (SBRT) for resectable liver oligometastatic MMR-proficient (pMMR) colorectal cancer (CRC): Final results.
Authors: Deming Dustin A. , Lubner Sam Joseph , Uboha Nataliya Volodymyrivna , Emmerich Philip , Kraus Sean , LoConte Noelle K. , Kim David H. , Matkowskyj Kristina A. , Weber Sharon , Abbott Daniel , Eickhoff Jens C. , Bassetti Michael F. 
Published: January 2023

161 Background: SBRT is a standard treatment option for oligometastatic CRC and is associated with an increase in immunogenic antigen release and influx of immune cells. We hypothesized that radiation would enhance the immunogenicity of pMMR CRC and potentiate the effectiveness of PD-1 blockade. This phase Ib study examined the safety and efficacy of the sequential combination of SBRT and Pem in patients (pts) undergoing resection of their disease. Additionally, the accumulation and proteolysis of versican (VCAN), an immunoregulatory tumor matrix proteoglycan was examined as a novel immunotherapy biomarker. Proteolysis of VCAN results in the release of an immunostimulatory fragment, versikine. Cancers with low VCAN and high versikine (VCAN proteolysis predominant (VPP)) are hypothesized to respond better to immunotherapies. Methods: Eligibility criteria included resectable liver-confined metastatic pMMR CRC. Prior surgery and systemic chemotherapy were allowed. Subjects received sequential SBRT and cycle 1 of Pem prior to operative management and adjuvant Pem. The primary objectives were to determine the safety/tolerability of this regimen and the recurrence free survival (RFS) at 1 year following operative management. Correlative studies examined tumor infiltrating CD8+ T lymphocytes (TILs), VCAN, and versikine using immunohistochemistry. Results: 15 pts (median age 61.5 [range 39-69], 26% female) were enrolled. All pts had prior FOLFOX. The number of liver lesions ranged from 1-6. SBRT median dose was 50 Gy (40-60 Gy) to 1-2 liver lesions. Grade 3/4 AEs included one case of biliary tract injury and biloma, and one case of G3 hypophosphatemia. No grade 3/4 immune-related AEs occurred. All pts completed a minimum follow-up of 1 year post resection (median follow-up 41 months [range 15-64]). In the intention to treat analysis, the 1 year RFS was 67% (historic control 50%), 40% of patients remained cancer free, and 67% of pts are still alive. 2 of 3 pts with BRAF V600E mutations have had early recurrences. 2 pts had VCAN high tumors and both recurred prior to 1 year. 6 pts had VPP cancers and 83% were recurrence free at 1 year and 66% are currently without evidence of cancer. Conclusions: The combination of SBRT with Pem was well tolerated with no signal of increased immunotherapy-related toxicity. This study met its primary endpoint and this regimen deserves further investigation in confirmatory studies. Additionally, VCAN accumulation and proteolysis are promising biomarkers in this setting. Clinical trial information: NCT02837263 .
Deep learning model for predicting treatment response for patients with rectal cancer using 3D medical imaging.
Authors: Lim June Hyuck , Heo Jaesung , Park Jeongmin , Kim Seonhwa , Jang Hanbyeol 
Published: January 2023

168 Background: We developed a deep learning model to predict pathological response based on magnetic 3D resonance imaging in rectal cancer. Methods: A total of 242 patients with locally advanced rectal cancer who received preoperative chemoradiotherapy followed by surgical resection were collected from single center. Surgical resection was performed at 6 to 8 weeks after the completion of preoperative CRT. Achieving pathogic complete response (pCR) was defined as complete absence of any tumour cells, in both the primary site and the dissected lymph node in surgical specimens. Based on pre-chemoradiotherapy T1-weighted axial 3D MR images, deep learning models were developed to predict pCR, respectively. Results: We analyzed 32,000 MRI images and involved several radiation oncologists in segmenation and classification. To calculate the probability of pCR using various convolutional neural network (CNN) architectures, several deep learning models were developed. The data input to the deep learning model was 3D MRI image, clinical data, and MRI metadata. Among 242 patients, 50 (20.7%) had evidence of pCR. The best model was developed based on SeResNet using transfer learning by MONA framework. The deep learning model showed an area under the receiver operating characteristic curve, sensitivity, specificity, and accuracy of 0.926, 0.831, 0.921, and 90.2% for predicting pCR. Conclusions: The pre-chemoradiotherapy T1-weighted 3D MR image-based deep learning model showed acceptable performance in predicting pCR in patients with rectal cancer.[Table: see text]
Feasibility of establishing and drug screening patient-derived rectal organoid models from pretreatment rectal cancer biopsies.
Authors: Acklin-Wehnert Scarlett , Dayanidhi Divya , Czito Brian G. , Palta Manisha , Willett Christopher , Eyler Christine Elissa , Mantyh Christopher , Migaly John , Thacker Julie , Lan Billy , Hsu David S. 
Published: January 2023

176 Background: Response to neoadjuvant chemotherapy and radiation therapy in the treatment of locally advanced rectal cancer is heterogenous and prognostic of clinical outcomes, necessitating the need for predictive biomarkers to guide personalized treatment recommendations. Sensitivity to a given chemotherapy in patient-derived organoids predicts patient response to that chemotherapy, establishing it as a promising model for efforts to ascertain predictive biomarkers and personalize treatment decisions. This study assessed the feasibility of obtaining patient-derived rectal organoids from standard of care pre-treatment proctoscopy biopsies. Methods: In this clinical trial (NCT04371198), biopsies were obtained from patients with stage II rectal adenocarcinoma prior to receipt of neoadjuvant therapy. Tissue samples were mechanically and enzymatically dissociated to obtain a single cell suspension. Cells were then mixed with matrigel at a ratio of 2,000 cells:5 µL Matrigel in a 50ul dome and plated on a 24 well tissue culture plate with colorectal cancer organoid media at 37oC/5% CO2. Established patient-derived organoids were then used to perform drug screens with clinically-applicable chemotherapeutics including oxaliplatin, irinotecan and 5-FU, followed by high throughput drug screen using our recently published MicroOrganoSpheres platform using the NCI Approved Oncology Drugs Set VI* library. Results: Of the 20 patients enrolled, 17 (85%) patient-derived organoids were created from pre-treatment specimens. 15 (88%) of these samples were successfully established as defined by the ability to passage organoids for at least two passages. All established samples were used to perform standard of care drug screens and high throughout drug screens, which demonstrated differences in drug sensitivities among the samples. Moreover, within two weeks of receiving the sample, four established quickly enough to complete drug screening with oxaliplatin, SN38, and 5-Fluorouracil. Conclusions: These results demonstrate the feasibility of establishing patient-derived rectal organoids from biopsy specimens obtained by proctoscopy, and reinforce the utility of patient-derived organoids as a tractable ex vivo platform to personalize rectal cancer treatment. Planned future directions include in vitro determination of radiation therapy sensitivity as well as systematic assessment of the correlation between individual patients and their organoid model. Clinical trial information: NCT04371198 .
TP53 gain of function mutation as a prognostic factor in high-methylated metastatic colorectal cancer: Translational research of TRICOLORE study.
Authors: Ouchi Kota , Wakayama Shonosuke , Takahashi Shin , Yamada Yasuhide , Komatsu Yoshito , Shimada Ken , Yamaguchi Tatsuro , Shirota Hidekazu , Takahashi Masanobu , Ishioka Chikashi 
Published: January 2023

179 Background: TP53 tumor suppressor gene is frequently inactivated by loss-of-function mutations. Some of the mutations gain additional oncogenic functions and are known as gain-of-function (GOF) mutations. This study analyzed the association among primary tumor site (PS), genome-wide DNA methylation status (GWMS), and TP53 mutation subtypes about prognosis in metastatic colorectal cancer (mCRC). Methods: Tumor tissues of mCRC patients registered in the TRICOLORE Study (clinical trial number) were analyzed for GWMS and TP53 mutation as translational research and were classified into high-methylated colorectal cancer (HMCC) and low-methylated colorectal cancer (LMCC) for GWMS, and wild-type , GOF mutation and non-GOF mutation for TP53 mutation. Overall survival (OS) was compared between single or combined subgroups, and Cox regression analysis was performed to identify factors contributing to OS. Results: A total of 209 patients were analyzed, HMCC and LMCC were 60 (28.7%) and 149 (71.3%), respectively. TP53 wild-type , GOF mutation and non-GOF mutation were 35 (16.7%), 79 (37.8%) and 95 (45.5%), respectively. HMCC showed a significantly worse prognosis than LMCC (median OS 25.3 vs. 40.3 months, P < 0.01, hazard ratio 1.87). Combining GWMS and TP53 mutation subtypes about prognosis, the HMCC/GOF (n = 26) group had a significantly poorer prognosis than the other three groups including HMCC/non-GOF (n = 22), LMCC/GOF (n = 53), and LMCC/non-GOF groups (n = 73) (median OS 17.7, 35.3, 40.3, 41.2 months, p = 0.007, p < 0.001, p < 0.001, respectively). The HMCC/GOF group had a poorer prognosis than the other 3 groups regardless of the PS. In the multivariate analysis in the GOF mutation subgroup, HMCC (p < 0.01) was the only poor prognostic factor, while right-sided colon cancer (p = 0.03) and RAS mutations (p = 0.01) were significant poor prognostic factors in the multivariate analysis in the non-GOF mutation subgroup. Conclusions: TP53 gain of function mutations are independent poor prognostic factors in high-methylated metastatic colorectal cancer.
Disparities in colorectal cancer: Trends of reduced screening among minority populations.
Authors: Ouni Ahmed , Cardiel Nunez Kristin , Garrett Aneesah , Heckman Michael , Brahmbhatt Bhaumik , Woodward Timothy A A 
Published: January 2023

18 Background: Studies have shown that African Americans (AA) are at increased risk for Colorectal Cancer (CRC) compared to other groups. Despite advancements in CRC screening modalities, few studies have investigated disparities in CRC screening among this vulnerable population. Methods: We performed a retrospective review of patients of age 45 or older who were seen in Family Medicine (FM), Internal Medicine (IM), or Gastroenterology (GI) between January 1, 2015 and December 31, 2021 at the Mayo Clinic. Information was collected regarding patient characteristics (age, sex, Charlson comorbidity score, race), and outcomes (whether a Cologuard test was ordered on the same day as the initial appointment, and whether the patient underwent a colonoscopy within 1 year after the initial appointment). Categorical variables were summarized with number and percentage of patients. Outcomes were compared between race groups (Caucasian, AA, Asian, Other) using unadjusted and multivariable logistic regression models. Multivariable models were adjusted for age, sex, and Charlson comorbidity score. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated. P-values <0.05 were considered as statistically significant, and all statistical tests were two-sided. Results: Overall, 558,078 were included for analysis and 14,607 (2.6%) were AA. Overall, AA patients for less likely to have Cologuard ordered compared to Caucasians (OR=0.62, p<0.001), notably driven by patient seen in the FM group (OR=0.54, p<0.001) and no statistically significant difference was observed in the IM and GI groups (p=0.055 and p=0.43, respectively). Notably, compared to Caucasian patients, Asian patients were overall more likely to have Cologuard ordered (OR=1.23, p=0.003). In multivariable analysis assessing the likelihood of having a colonoscopy performed within 1 year of the initial appointment, the likelihood of a colonoscopy within 1 year of initial clinic visit was significantly lower for AA compared to Caucasian patients (OR=0.50, p=0.028). This difference was strongest in FM patients (OR=0.26, p=0.022) and was not significant for IM (OR=0.67, p=0.37) or GI (OR=2.31, p=0.25). Conclusions: In this study, we found that AA ethnicity is associated with reduced likelihood of having Cologuard ordered compared to Caucasian patients. Furthermore, AA patients were less likely to have colonoscopy ordered within 1 year of initial visit clinic visit among the overall cohort, highlighting important disparities in CRC screening among this vulnerable patient population notably for those seen in the FM group. Future studies are needed to assess other barriers for CRC screening in this population.
Feasibility of circulating tumor DNA (ctDNA) to guide organ preservation in patients with node-negative rectal cancer undergoing neoadjuvant chemotherapy, excision, and observation in the phase II CCTG CO.28 trial.
Authors: Loree Jonathan M. , Madison Russell , O'Callaghan Christopher J. , Brown Carl J , Tu Dongsheng , Jonker Derek J. , Sherry Max , Fine Alexander D. , Huang Yanmei , Camara William , Pokharel Prapti , Aleshin Alexey , Oxnard Geoffrey R. , Kennecke Hagen Fritz 
Published: January 2023

180 Background: CCTG CO.28 evaluated 3 months of neoadjuvant CAPOX or FOLFOX followed by transanal excision surgery (TES) in patients (pts) with T1-T3, N0 rectal cancers with the goal of organ preservation. Total mesorectal excision (TME) was recommended for inadequate downstaging or high-risk features on TES pathology. Detection of ctDNA is associated with a high rate of recurrence in high risk resected colorectal cancer. However, the sensitivity of ctDNA in early-stage rectal cancer is unclear. Methods: Tissue CGP was performed retrospectively on pretreatment resected tumor using Foundation OneCDx (F1CDx), followed by MRD detection using FoundationOneTracker. Briefly, variants were selected from F1CDx using an algorithm that filters out non-tumor derived variants (e.g. germline). A tumor-informed personalized multiplex PCR-next generation sequencing assay, consisting of up to 16 variants, was used to detect ctDNA and quantify plasma mean variant allelic frequency (VAF) and mean tumor molecules per mL of plasma (MTM/mL). FoundationOneTracker was performed on blood samples collected pre/post-neoadjuvant chemotherapy. Buffy coat sequencing was performed at FMI to validate the monitoring variant selection algorithm. Results: 52 pts underwent F1CDx and FoundationOneTracker analysis. KRAS mutations were observed in 60% (n =31) of cases; MSI-H and BRAF V600E mutations were not detected. From 1,580 distinct variants detected in tissue and paired buffy coat sequencing, 985 had VAF >30% in the buffy coat specimen and were considered germline. The variant selection algorithm filtered 99.8% (n = 983) of germline variants; the remaining 2 were not selected for primer design. A median of 7 variants (range 2-16) were tracked per pt. Detectable ctDNA was found in 0% (0/6), 19% (6/32) and 55% (6/11) of treatment naïve T1, T2 and T3ab cases, respectively, and 83% of those which were initially positive (10/12) cleared ctDNA post chemotherapy. Three pts had detectable ctDNA pre-excision, including 1 who was negative pretreatment. From 42 pts with pre/post-treatment plasma, 19 pts were recommended for TME; 2 had detectable ctDNA, 5 had ctDNA clearance, and 12 had no ctDNA detection. Conclusions: Node-negative rectal cancer exhibited ctDNA shed in a minority of pts, with most clearing ctDNA on chemotherapy before their TES. The dynamic ctDNA signal we demonstrate could supplement clinical factors in informing organ preservation in very early-stage rectal cancer. Larger studies are needed to determine if this information can be used to personalize therapy. Clinical trial information: NCT03259035 . [Table: see text]