bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival analysis and associated factors in metastatic early-onset colorectal cancer vs. metastatic average-onset colorectal cancer.
Authors: Jeri-Yabar Antoine , Vittini Liliana , Prado-Nuñez Sebastian , Dharmapuri Sirish 
Published: June 2024

e15549 Background: Early-onset colorectal cancer (EO-CRC) is defined as colorectal cancer diagnosed before age 50 and its incidence has been increasing during the last decade. Average-onset colorectal cancer (AO-CRC) has presented a steady decline in incidence and related mortality over the past 20 years. There is controversy surrounding the disparities in outcomes and overall survival (OS) in EO-CRC vs. AO-CRC. Our study compared the OS and cause-specific survival (CSS) between metastatic EO-CRC (mEO-CRC) and metastatic AO-CRC (mAO-CRC) and identified associated factors. Methods: Data on patient characteristics, tumor characteristics, incidence and mortality were obtained from the SEER database from 2010 to 2020. We identified 23,278 individuals aged > 18 with confirmed diagnosis of all histologic subtypes of metastatic CRC (M1 on TNM stage) using ICD-O-3 site code C180, C182-9, C209 and histology codes: 8000, 8010, 8012, 8013, 8020-2, 8031-33, 8041, 8045, 8070-2, 8083, 8123-4, 8140, 8144-45, 8201, 8210-11, 8213, 8220-1, 8240, 8243-46, 8249, 8253, 8255, 8260-3, 8261-3, 8265, 8310, 8323, 8480-1, 8490, 8507, 8510, 8550, 8560, 8570, 8574, 8936, 8980. OS distributions and CCS were conducted using the Kaplan-Meier method and log-rank test was used to assess differences between mEO-CRC and mAO-CRC. Cox regression model used to assess associations between variables. Results: mEO-CRC constituted 17.79% of the cases, while 82.21% were mAO-CRC. Most patients with mEO-CRC were between 45-49 years old (47.66%), males (52.16%), white (72.57%), with histology of adenocarcinoma (87.30%). Left colon tumors were most prevalent in both groups (40.26%), but higher among mEO-CRC than in mAO-CRC (49.63% vs 38.23%, p < 0.001). mEO-CRC were more likely to receive chemotherapy (87.23% vs. 66.66%, p < 0.001) and radiotherapy (14.92% vs. 9.51%, p < 0.001), while surgery was similar in both groups (87.71% vs. 88.52%, p = 0.140). Patients with mEO-CRC had a higher OS (HR: 1.53, CI 95% 1.47-1.59, p < 0.001), as well as a higher CSS (HR: 1.33, 95% CI: 1.27-1.39, p < 0.001) when compared to mAO-CRC. mEO-CRC also had a significantly better median overall survival (30 months vs. 18 months p < 0.001). Factors associated with worse OS include mAO-CRC (p < 0.001), mucinous adenocarcinoma (p < 0.001), male sex (p 0.003) and no surgical intervention (p < 0.001). Conclusions: Patients with mEO-CRC had better OS and CSS when compared to patients with mAO-CRC and were more likely to receive cancer-directed therapy which could be explained by the mEO-CRC cohort having a higher performance status, less comorbidities, and better tolerance to cancer-related therapy. Factors associated with worse OS and CSS are mAO-CRC, mucinous adenocarcinoma, male sex and lack of surgical intervention. Furthermore, it is crucial to continue studying potential candidates who would benefit from early CRC screening.
Modified FOLFOXIRI plus bevacizumab as a salvage regimen for patients with refractory metastatic colorectal cancer.
Authors: Ou Yuxuan , Zhang Jianwei , Cai Yue , Hu Huabin , Xie Xiaoyu , Ling Jiayu , Deng Yanhong 
Published: June 2024

e15559 Background: The triplet FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab showed improved outcomes for patients with metastatic colorectal cancer (mCRC) as first-line systemic treatment. However, those who progressed on standard therapies still faced the lack of optimal treatments in the third or later lines. There is a lack of data on applying triplet chemotherapy plus bevacizumab in later-line settings. We conducted a retrospective study to evaluate the efficacy and safety of modified FOLFOXIRI (mFOLFOXIRI) plus bevacizumab as a salvage regimen for patients with refractory metastatic colorectal cancer. Methods: Patients with refractory mCRC were retrospectively analyzed, who received mFOLFOXIRI plus bevacizumab in the third or later lines. The key inclusion criteria were:(1) 15-75 years old; (2) histologically confirmed mCRC; (3) treatment failure to at least two lines of treatments containing oxaliplatin, irinotecan, and 5-FU. Those with poor general condition (ECOG score > 2), or continuous grade 3-4 neuropathy and allergy to oxaliplatin were excluded. The mFOLFOXIRI regimen consists of oxaliplatin 85 mg/m² intravenous infusion for 2 hours; irinotecan 150 mg/m² intravenous infusion for 90 min; following intravenous infusion of leucovorin 400 mg/m² for 2 hours then 5-FU 2400 mg/m² for 46–48 hours continuous intravenous infusion, Q2W. Bevacizumab 5 mg/kg was administered by intravenous infusion Q2W. Results: 95 patients treated between January 2020 and December 2022 were retrospectively studied. The median age at diagnosis was 50.8 years (range 23-72 years). 50.5% of the patients had previously received at least four regimens. At the last follow-up date on December 31, 2023, the objective response rate (ORR) was 11.6% (1 complete response and 10 partial responses) and the disease control rate (DCR) was 68.4% (54 stable diseases). The median progression-free survival (PFS) was 6.2 months (95% CI, 5.4-7.0) and the median OS was 13.6 months (95% CI, 12.2-14.9). The most common adverse event was neutropenia (23.2%). Grade 3-4 adverse events were reported in 37 (38.9%) patients, including neutropenia (9.5%), oxaliplatin-related allergy (7.4%), thrombocytopenia (4.2%), thrombocytopenia (4.2%), diarrhea (4.2%), anemia (3.2%), nausea (3.2%), and neuropathy (2.1%). Conclusions: Modified FOLFOXIRI plus bevacizumab is effective as a salvage regimen in patients with refractory mCRC and with an acceptable safety profile.
FOLFOXIRI/bevacizumab (bev) versus doublets/bev as initial therapy of unresectable liver-only, right-sided and/or RAS or BRAF mutated (mut) metastatic colorectal cancer (mCRC): An individual patient data-based pooled analysis of randomized trials.
Authors: Antoniotti Carlotta , Marmorino Federica , Meinert Fabian Maximilian , Bergamo Francesca , Tonini Giuseppe , Rossini Daniele , Borelli Beatrice , De Rosa Antonio , Allegrini Giacomo , Stein Alexander , Moretto Roberto , Ronzoni Monica , Zaniboni Alberto , Germani Marco Maria , Sperotto Sara , Ongaro Elena , Ghelardi Filippo , Masi Gianluca , Schmoll Hans , Cremolini Chiara 
Published: June 2024

e15563 Background: FOLFOXIRI/bev was associated with longer PFS and OS versus doublets/bev independently of the presence of liver-limited disease or not, and the secondary resection of metastatic lesions. Recently, in the CAIRO-5 study patients with liver-limited right-sided and/or RAS or BRAF mutated mCRC experienced no OS difference, but higher ORR, R0 resection rate, and longer PFS with the triplet/bev when compared with doublets/bev. Here we aim at providing an estimation of the efficacy and activity of FOLFOXIRI/bev over doublets/bev in patients with unresectable liver-only, right-sided and/or RAS or BRAF mut mCRC. Methods: We selected pts with liver-only, right-sided and/or RAS or BRAF mut mCRC, and treated with first-line doublets/bev or FOLFOXIRI/bev in four phase II or III randomized controlled trials (RCTs): TRIBE (NCT00719797), TRIBE2 (NCT02339116), CHARTA (NCT01321957), and STEAM (NCT01765582). Patients included in these RCTs were deemed initially unresectable according to a multidisciplinary evaluation and were not selected based on the potential conversion to resectability. We compared FOLFOXIRI/bev with doublets/bev in terms of PFS, OS, ORR, and R0 resection. Results: A total of 300 pts were eligible. The median age was 61 years and most of them had an ECOG performance status of 0 (83%) and synchronous metastases (91%). One hundred and thirty (43%) and 170 (57%) pts received doublets/bev and FOLFOXIRI/bev, respectively. Baseline characteristics were homogeneous between the two treatment groups. Pts receiving FOLFOXIRI/bev showed longer PFS (12.3 vs 10.3 months [mos] HR:0.75, p = 0.019) and a statistically not significant trend for better OS (29.1 vs 23.2 mos, HR:0.85, p = 0.253), than those treated with doublets/bev. FOLFOXIRI/bev was also associated with higher ORR (64% vs 53%, OR:1.54, p = 0.076) and no differences in R0 resection rate (27% vs 24%, OR:1.15, p = 0.696) was reported. No significant interaction was found between treatment effect and the achievement of R0 resection in terms of both PFS (Pinteraction:0.81) and OS (Pinteraction:0.53). Conclusions: As compared to doublets/bev, upfront FOLFOXIRI/bev provides a meaningful advantage to pts with initially unresectable, liver-only, right-sided and/or RAS or BRAF mut mCRC, in terms of activity and efficacy, thus corroborating the choice of this regimen as upfront treatment for these pts, regardless of the opportunity to achieve the R0 secondary resection of their liver metastatic lesions.
Bowel bag sparing in palliative radiotherapy (pRT) of rectal cancer (rCa): Tradeoff between organs at risk (OARs) and use of AI to reduce radiation oncologist (RO) workload.
Authors: Fredén Emil , Knutsson Johan , Yousif Rafat , Siegbahn Albert , Lind Pehr A. 
Published: June 2024

e15615 Background: We retrospectively studied the potential to reduce bowel toxicity after pRT of rCa using a bowel dose (BD) minimization strategy; also its effect on dose to remaining normal tissues (NT) and pelvic bone marrow (PBM). Finally, we studied the use of AI to reduce the RO workload. Methods: 25 consecutive rCa patients (pts) previously treated with pRT were included. Their treatments were planned without consideration to BD. The following OARs were manually segmented retrospectively: Bowel Bag (BB-M) excluding PTV, PBM (PBM-M), and NT defined as the patient contour excluding PTV and BB-M. The AI-Rad Companion software was used to autosegment: Bowel Loops (BL-AI) and PBM (PBM-AI). For the 25 pts, two Pareto optimal treatment plans (5 Gy x 5) were generated with the Monaco treatment planning system. The first plan (Reference) was optimized aiming to limit dose outside the PTV. The second plan (Opt-BB-M) was optimized aiming firstly to limit BB-M dose and secondly to limit NT dose. A third plan (Opt-BL-AI) was generated for the 10 worst-off pts (in terms of BD) aiming instead to limit BL-AI dose. Two volume-at-dose (VD) metrics (V18Gy, V10Gy) were used as endpoints. Endpoint differences (ΔVD-OAR) were tested using one-sided Wilcoxon signed-rank tests. Spearman (rs) and Pearson (r) correlation coefficients were used to study correlation between variables (ΔVD-BB vs. ΔVD-BM, and ΔVD-BB vs. ΔVD-NT). Dice Similarity Coefficient (DCS) was used to compare PBM-M and PBM-AI. Results: After reoptimization, BB-M VD (V18Gy; V10Gy) was lower (p < 0.001; p < 0.001), PBM-M VD was higher (p = 0.002; p < 0.001), and NT VD was higher (p < 0.001; p < 0.001). For BB-M, ΔV18Gy and ΔV10Gy (median, min, max) were (-4, -46, 0) cm3 and (-33, -254, 0) cm3; for PBM-M: (+2, -4, +56) cm3 and (+33, -6, +189) cm3; for NT: (+10, -43, +194) cm3 and (+146, -18, +614) cm3. Table 1 presents results for the 10 worst-off pts. Medium/strong correlations were found for ΔV18Gy-BB vs. ΔV18Gy-PBM (rs = -0.72, p < 0.001; r = -0.74, p < 0.001), ΔV10Gy-BB vs. ΔV10Gy-PBM (rs = -0.66, p < 0.001; r = -0.32, p = 0.11), ΔV18Gy-BB vs. ΔV18Gy-NT (rs = -0.74, p < 0.001; r = -0.74, p < 0.001), ΔV10Gy-BB vs. ΔV10Gy-NT (rs = -0.74, p < 0.001; r = -0.51, p = 0.009). The DSC (median, min, max) for PBL was (92%, 87%, 94%). Conclusions: Bowel dose in pRT of rCa can be reduced at the expense of increasing dose to PBM and other NT. AI tools can be used effectively to limit RO workload. [Table: see text]
Transanal endoscopic microsurgery vs. radical surgery for mid-low rectal cancer in patients with clinical complete or near-complete response after neoadjuvant chemoradiotherapy.
Authors: Qiu Xiaoyuan , Zhou Jiaolin , Xiao Yi , Qiu Huizhong , Shen Zhan , Wu Bin , Jia Wenzhuo , Niu Beizhan , Li Fei , Yao Hongwei , WU Aiwen , Hu Ke , Xue Huadan , Zhou Weixun , Lin Guole 
Published: June 2024

e15616 Background: Following neoadjuvant chemoradiotherapy (nCRT), total mesorectal excision surgery used to be the standard therapy for locally advanced rectal cancer (LARC). However, the radical surgery is associated with high complication rates and impairs patients' quality of life, especially for non-sphincter preservation procedures. For the past two decades, nCRT followed by organ preservation strategies like watch-and-wait (W&W) or local resection offers an alternative for patients being clinically evaluated with complete response or near complete response, however the oncological outcomes of these approaches require further exploration. Methods: We prospectively collected data on 80 patients with T3-4N0M0 or TanyN+M0 mid-low rectal cancer who achieved cCR or near-cCR after nCRT from May 2017 to September 2021 at 5 tertiary centers in China. Patients were divided into the TEM group (group A) or the radical surgery group (group B). Clinicopathological features, operative outcomes, oncological and functional results were analyzed. Results: A total of 76 cases were analyzed, with 38 in each group. Baseline characteristics were comparable between the two groups. Postoperative histology revealed 22 ypT0Nx(57.9%), 5 ypT1Nx(13.2%), 10 ypT2Nx (26.3%), 1 ypT3Nx(2.6%) in group A, and 18 ypT0N0 (47.4%), 5 ypT1N0 (13.2%), 11 ypT2-3N0 (28.9%), 1 ypT0N1 (2.6%), 3 ypT2-3N1 (7.9%) in group B. After a median follow-up of 61 months, 2 patients (5.26%) in group A experienced local recurrence, while none in group B. 8 patients (21.05%) in group A developed distant metastases compared to 5 (13.16%) in group B. There was no statistically significant difference between two groups in 5-year disease-free survival(P = 0.320), or 5-year overall survival (P = 0.425). Patients in group A had significantly faster postoperative recovery and a superior quality of life evaluated by the Wexner and LARS scores compared to group B. Conclusions: For cCR and near-cCR LARC patients after nCRT, organ preservation with TEM may serve as a staging method to evaluate local tumor persisrence. And it provides an alternative therapy for carefully selected patients who have needs to preserve sphincteric function or can’t tolerate radical resection, without significantly compensate long-term oncological outcomes. This strategy could relatively safely enable sphincteric function preservation for these patients with faster postoperative recovery and better quality of life. Clinical trial information: NCT03042000 .
Metabolic disorders in patients diagnosed with colorectal cancer.
Authors: Levy Julia A. , Lorona Nicole C. , Gigic Biljana , Li Christopher I. , Ose Jennifer , Shibata David , Siegel Erin M. , Toriola Adetunji T. , Ulrich Cornelia M , Hardikar Sheetal , Figueiredo Jane C. 
Published: June 2024

e15618 Background: Colorectal cancer (CRC) is the third most common cancer globally and ranks second as a cause of cancer-related death. As survival rates among CRC patients continue to rise, addressing accompanying metabolic comorbidities is becoming increasingly important. This study aims to explore the prevalence of metabolic comorbidities and metabolic syndrome among CRC patients, as well as their impact on survival. Methods: The ColoCare Study is a prospective cohort study conducted across seven U.S. and European sites. Data from a single site, Cedars-Sinai Medical Center in Los Angeles, California was analyzed. Adults with newly diagnosed stage I-IV CRC and available medical records were eligible. Basic demographic information and medical history, including hypertension, hyperlipidemia, and diabetes mellitus (DM) diagnosis at or before CRC diagnosis were collected by manually reviewing electronic medical records. Additionally, BMI was calculated using patients' weight and height at the time of diagnosis and classified according to the CDC’s published ranges. Patients were considered to have metabolic syndrome if they met three or more of the following criteria: hypertension, hyperlipidemia, DM, or obesity. Overall survival rates for patients with each metabolic condition were compared. Results: A total of 295 patients (58.3% male, 41.7% female, mean age at diagnosis = 58.3) were identified. 172 were non-Hispanic White (58.3%), 52 were Hispanic/Latino (17.6%), 36 (12.2%) were Asian, 27 (9.2%) were Black, and 8 (1.8%) were unknown/other. Metabolic conditions were prevalent in the cohort: hypertension affected 33.9%, hyperlipidemia affected 21.4%, and DM affected 13% of patients. Additionally, over half of the patients (56.6%) were overweight or obese. Individuals meeting criteria for metabolic syndrome (8.8%) had lower survival rates compared to those without this condition (73.1% vs. 81.4%). Similarly, patients with DM had lower survival rates compared to their counterparts without DM (72.5% vs. 82.0%). Patients with hypertension, hyperlipidemia, and elevated BMI did not have significantly different survival rates compared to patients without such conditions. Conclusions: Our study highlights the prevalence of metabolic comorbidities, specifically metabolic syndrome and DM, among CRC patients and emphasizes how these factors can impact patient outcomes post-diagnosis. This information is valuable for physicians when considering lifestyle changes or treatment strategies following CRC diagnosis. Further, it highlights the importance of coordination between oncologists and primary care providers to effectively manage metabolic diseases in CRC patients.
The safety and efficacy of immune checkpoint inhibitor in combination with FOLFOX as neoadjuvant/adjuvant therapy in patients with locally advanced colon cancer.
Authors: Cai Changjing , Han Ying , Peng Yinghui , Zhang Xiangyang , Gan Pingping , Tang Youhong , Tang Lanhua , Liu Yiping , Shen Hong , Zeng Shan 
Published: June 2024

e15621 Background: The recurrence rate of locally advanced colon cancer (T3-4 or N+, M0) after surgery is significantly high. Emerging data indicate that the combination of immunotherapy and chemotherapy demonstrates synergistic effects in other solid tumors. Consequently, a combination of immunotherapy and chemotherapy holds the potential to benefit patients with MSS and pMMR colon cancer. We have designed a prospective trial to investigate whether the immune checkpoint inhibitor (ICI) in combination with chemotherapy represents a safe and beneficial treatment approach for locally advanced colon cancer. Methods: Inclusive Criteria: Patients with locally advanced colon cancer (T3-4 or N+, M0) confirmed through pathological biopsy, with confirmed indications for neoadjuvant/adjuvant chemotherapy by the multidisciplinary team. Patients must be eligible for surgery, and a measurable mass must be identified according to RECIST version 1.1. All individuals aged over 18 years, with an estimated life expectancy of over one year and an ECOG score within 0-1, are eligible. The neoadjuvant chemoimmunotherapy group (NACI) includes mFOLFOX 6 (Q2W) and the anti-PD-1 monoclonal antibody (Toripalimab) (3mg/kg, Q2W), while the neoadjuvant chemotherapy group (NAC) receives only mFOLFOX 6 for neoadjuvant/adjuvant therapy (a total of 12 cycles, 6 cycles pre-surgery and 6 cycles post-surgery). The primary endpoint is the pathological complete response (pCR) rate. Results: From 2019 to 2022, a total of 22 patients were enrolled in the study, with 13 in the NACI group and 9 in the NAC group. The research findings indicate that in the NACI group, over 30% (4/13) of patients achieved a pathological complete response (pCR), whereas none of the patients in the NAC group reached pCR (0/9). Among the pCR patients, one was identified as MSI-H/dMMR, two as MSS/pMMR, and one had an unknown status. Tumor regression grade (TRG) levels also revealed that all patients in the NACI group were below grade 2, significantly outperforming the NAC group (P < 0.05), with statistically significant differences. However, no significant differences were observed between the NAC and NACI groups in terms of CT regression percentage, R0 resection, vascular cancer emboli, and the level of neural invasion. Adverse reactions did not show significant differences between the two groups. Conclusions: The combination of immunotherapy and chemotherapy exhibits a synergistic effect in treating locally advanced colorectal cancer. Tolerable adverse reactions suggest that neoadjuvant chemoimmunotherapy could potentially serve as a novel therapeutic option. Clinical trial information: NCT03985891 .
The relationship between mismatch repair (MMR) proteins status and the response to conventional neoadjuvant therapy in colorectal cancer (CRC).
Authors: Weng Junyong , Zhang Ruoxin , Zhu Zhonglin , Li Shanbao , Ye Zilan , Liu Qi , Li Xinxiang 
Published: June 2024

e15627 Background: MMR proteins status is not routinely detected in CRC patients. Neoadjuvant use of immune checkpoint inhibitors (ICIs) in deficient mismatch repair (dMMR) CRC patients can achieve a pathological complete response (pCR) rate of 60-100%. Conversely, dMMR/MSI-H patients may exhibit a poor response to conventional neoadjuvant therapy, although supporting evidence is limited. Methods: We retrospectively collected clinical data from patients who underwent neoadjuvant chemoradiotherapy or chemotherapy at Fudan University Shanghai Cancer Center from 2008 to 2021, excluding those who received neoadjuvant ICIs. MMR proteins were detected using immunohistochemistry on surgical samples or preoperative colonoscopy biopsy samples, and some patients underwent genetic testing to evaluate their microsatellite status. This study included M0 CRC patients with complete tumor regression grading (TRG) assessment and MMR/MSI status. Responses were assessed using TRG evaluation (AJCC-TRG system) on the primary tumor. Results: Among 1005 patients, the median age was 57 years (range: 19-95), with 643 males (64.0%) and 362 females (36.0%). Seventy-two (7.2%) had right colon cancer, 80 (8.0%) had left colon cancer, and 853 (84.9%) had rectal cancer. Fifty-five (5.5%) had dMMR, and 950 (94.5%) had proficient mismatch repair (pMMR). In dMMR patients, defective proteins included hMLH1 and PMS2 combined in 22 patients, hMSH6 in 14 patients, PMS2 in 9 patients, hMSH6 and hMSH2 combined in 6 patients, hMLH1 in 2 patients, hMLH1 and hMSH6 combined in 1 patient, and hMSH6, PMS2, and hMSH2 combined in 1 patient. Compared to pMMR patients, dMMR patients showed either no response or poor response to conventional neoadjuvant therapy, with no patients exhibiting TRG = 0/1. One hundred and eleven (11.7%) pMMR patients showed a good response (TRG = 0/1). There was no statistically significant difference in overall survival between the two groups of patients (HR, 1.547; 95% CI: 0.9221-2.596; P = 0.172). Conclusions: Although our study is retrospective and some patients with pCR lacked MMR expression information, we can still conclude that dMMR patients have a poor response to conventional neoadjuvant therapy, and neoadjuvant ICIs treatment may be a better choice for dMMR patients. We recommend routine immunohistochemistry of MMR proteins in preoperative colonoscopies to guide the development of neoadjuvant strategies. [Table: see text]