tbuckley/cabot-search huggingface dataset:
Rising trend of early-onset colorectal cancer in the US: Incidence and projections to 2030.
Authors: Chun-Wei Pan, Adrian Villaroman, Maria Cristina Cuartas, Shweta Gupta
Journal: Journal of Clinical Oncology (2024)

e15523 Background: Colorectal cancer (CRC) remains a critical health issue in the United States, particularly notable for its rising incidence in individuals under 55 years. Factors such as lifestyle habits, and genetic predispositions may contribute to pathogenesis while inadequate screening protocols may lead to delayed diagnoses in this younger demographic. Currently, the initial CRC screening guidelines recommend lowering the start age to 45. We seek to provide current data on the US CRC incidence and estimate the burden by 2030. Methods: Using the CDC National Center of Health Statistics database, we queried the incidence rates of CRC from 1999 to 2020. These are reported in Crude rate and age-adjusted rates to standard year 2000 populations per 100,000 person-years. The Autoregressive Integrated Moving Average model was used to predict the projected incidence rate by 2030. R software version 2023.09 was used for analysis. Results: The study identified 3,201,843 CRC cases from 1999-2020, with a notable increase in incidence rates, especially in younger demographics. The largest increase was in the 30-34 age group, with an AAPC of 2.76, followed by the 25-29 and 35-39 age groups, with AAPCs of 2.57 and 2.24, respectively. In contrast, older age groups showed a decline, with the 75-79 age group decreasing from 9.20 to 3.76, and an AAPC of -4.05%. By 2030, early-onset colorectal cancer is expected to rise, particularly in the 40-44 age group (AAPC of 3.26%) and the 35-39 age group (AAPC of 2.92%). The increase is projected mainly in the 25-54 age groups. Conversely, older populations, particularly the 75-79 age group, are projected to see a decrease in incidence rates, from 3.76 to 1.17 per 100,000 by 2030. Conclusions: Our study highlights a significant rise in early-onset CRC, especially in the 25-54 age group, with an increasing projection by 2030 while older age groups are expected to experience a decrease in incidence rates. Consideration should be given to expanding CRC screening in patients younger than 45. [Table: see text]
Comparing the efficacy and safety of HepaSphere drug-eluting bead transarterial chemoembolization combined with hepatic arterial infusion chemotherapy versus hepatic arterial infusion chemotherapy alone in unresectable colorectal liver metastases.
Authors: Aiwei Feng, Song Gao, Jianhai Guo, Fuxin Kou, Shaoxing Liu, Xin Zhang, Baojiang Liu, Xiaodong Wang, Hui Chen, Haifeng Xu, Peng Liu, Guang Cao, Qinzong Gao, Xu Zhu
Journal: Journal of Clinical Oncology (2024)

3565 Background: Drug-eluting bead transarterial chemoembolization (DEB-TACE) and hepatic arterial infusion chemotherapy (HAIC) are widely employed treatments for unresectable colorectal liver metastases (CRLM). Limited evaluation exists regarding TACE plus HAIC versus HAIC alone. This study aimed to evaluate the efficacy of combining HepaSphere DEB-TACE with HAIC compared to HAIC alone in patients with unresectable CRLM. Methods: A total of 259 CRLM patients aged over 18 years, treated at Peking University Cancer Hospital between March 2015 and November 2022, were included in this retrospective study. Among them, 157 patients received HepaSphere DEB-TACE combined with HAIC (DEB-TACE-HAIC), while 102 patients received HAIC alone. Propensity score matching (PSM) was performed to avoid selection bias and enable comparative analysis of efficacy and safety between the two cohorts. The primary endpoint was progression-free survival (PFS), while secondary endpoints comprised hepatic progression-free survival (hPFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: PSM resulted in 83 pairs, achieving comparable baseline between DEB-TACE-HAIC and HAIC cohorts. Of these pairs, 116 were male and 50 were female. Notably, 51.2% of patients harbored mutations in either KRAS, NRAS, or BRAF genes. Prior to enrollment, 94.6% of patients had received systemic treatments. Median hPFS, PFS and OS were all higher in the matched DEB-TACE-HAIC cohort (median hPFS: 7.6 vs. 4.1 months, P=0.023; median PFS: 5.1 vs. 3.5 months, P=0.092; median OS: 15.5 vs. 14.7 months, P=0.513). ORR was 37.3% in the DEB-TACE-HAIC group and 27.7% in the HAIC group, with DCR of 75.9% and 69.9%, respectively. There were no treatment related deaths. Serious adverse events were comparable between the two groups, except for nausea, which occurred more frequently in the HAIC group (39.8% vs. 22.9%, P=0.019). Conclusions: DEB-TACE-HAIC demonstrated superior survival compared to HAIC alone in unresectable CRLM, even in patients refractory to systemic therapy. The combination of HepaSphere DEB-TACE and HAIC appears promising as a regional treatment option with improved outcomes and a comparable safety profile.
Short-course radiotherapy (SCRT) followed by fruquintinib plus adebrelimab and CAPOX in the total neoadjuvant therapy of locally advanced rectal cancer (LARC): A multicenter, single-arm, open-label, phase II study.
Authors: Zhenyu Lin, Peng Zhang, Kaixiong Tao, Tao Zhang
Journal: Journal of Clinical Oncology (2024)

TPS3643 Background: For LARC patients (pts), long-course concurrent chemoradiotherapy or SCRT followed by chemotherapy is recommended by the NCCN guidelines (Version 1.2024) as neoadjuvant therapy. Compared with chemoradiotherapy, the addition of immune checkpoint inhibitors (ICIs) or anti-angiogenic drugs could further improve complete response (CR) rate in the neoadjuvant treatment of LARC. Fruquintinib, a highly selective small-molecule inhibitor of VEGFR-1, -2, and -3, has gained FDA approval for pts with metastatic colorectal cancer previously treated. For pts with LARC at high risk of recurrence, the CR rate of SCRT followed by chemotherapy was 29%. There is an urgent need for new therapeutical options to improve the CR rate in these pts. This study introduces an innovative approach, combining SCRT, chemotherapy, Fruquintinib, and ICIs as a total neoadjuvant therapy for high-risk LARC pts. Methods: This is a multicenter, single-arm, open-label, phase II study (NCT06234007) investigating the efficacy and safety of SCRT sequential fruquintinib, combined with adebrelimab (an anti-PD-L1 monoclonal antibody) and CAPOX in pts with LARC. Eligible participants were 18 years or older, with an ECOG PS of 0–1, and a biopsy-proven, newly diagnosed, primary, LARC, classified as high risk on pelvic MRI (with at least one of the following criteria: clinical tumour [cT] stage cT4a or cT4b, extramural vascular invasion, clinical nodal [cN] stage cN2, involved mesorectal fascia, or enlarged lateral lymph nodes), were mentally and physically fit for surgery. Total neoadjuvant therapy included SCRT (5 × 5 Gy over 5 days, 1-week rest) followed by six cycles of fruquintinib (4mg, qd, po, q3w. For the initial 6 pts in the safety run-in period, dosage was adjusted based on dose-limited toxicities in the 1 st cycle) combined with adebrelimab (1200mg, iv, d1, q3w) and CAPOX (q3w). Subsequently, pts who did not reach clinical CR underwent total mesorectal excision, others received the “Watch and Wait” policy or surgery. Primary endpoint was CR rate (including clinical CR &amp; pathologic CR). Secondary endpoints included 3-year event free survival rate, overall survival, R0 resection rate and adverse events (AEs). Exploratory endpoints aimed to evaluate the correlation between potential biomarkers and efficacy. Using PASS 15 software (version 15.0.5.0), in the Tests for One Proportion analysis, with a two-sided α of 5% and to guarantee the power over 80%. The null hypothesis of CR rate was 29%, and the alternative hypothesis was 51%, accounting for a 10% drop-out rate, resulting in a sample size of 39 pts. With the 6 pts in the safety run-in period, a total of 45 pts would be enrolled in the study. Until Feb 1, 2024, 7 of planned 45 pts have been enrolled. Clinical trial information: NCT06234007 .
Phase II study of neoadjuvant short-course radiotherapy combined with CAPEOX plus envafolimab in patients with microsatellite stable locally advanced rectal cancer: Updated results of PRECAM study.
Authors: Sheng Dai, Fei Wang, Yiming Lv, Feixiang Zhang, Liming Shi, Yunfei Wang, Yanbin Shen, Lingna Xu, Peng Hu, Wen Tang, Dengyong Xu, Lina Shan, Xiya Jia, Yiyi Chen, David W. Larson, Da Wang, Weifeng Lao, Hongcang Gu, Xiaonan Sun, Xuefeng Huang
Journal: Journal of Clinical Oncology (2024)

3614 Background: Conventional neoadjuvant chemoradiotherapy (nCRT) yields a pathologic complete response (pCR) rate of about 15%–- 30% for locally advanced rectal cancer (LARC). This PRECAM study aimed to investigate the efficacy and safety of neoadjuvant short-course radiotherapy combined with CAPEOX plus Envafolimab in Patients with Microsatellite Stable (MSS) LARC, redefining the standard of care (SOC) for LARC. Methods: The study is an open-label, prospective, single-arm, phase II clinical study . Eligible patients with MSS LARC were consecutively enrolled. Participants received short-course radiotherapy (25Gy/5f) with subsequent two cycles of CAPEOX (capecitabine and oxaliplatin) and 6 cycles of Envafolimab (subcutaneous injection, 150 mg, QW ) followed by total mesorectal excision surgery. The primary endpoint was pathological complete response (pCR) rate, and the secondary endpoint was major pathologic (MPR) rate and safety. Results: From April to December 2022, 34 patients were enrolled, of whom 32 completed the study. Remarkably, The pCR rate was62.5% (20/32), and the (MPR) rate was 75% (24/32). Furthermore, 65.6% (21/32) patients achieved a neoadjuvant rectal (NAR) score below 8, suggesting an effective treatment response. Common adverse events included tenesmus (78.1%), diarrhea (62.5%), and leukocyte decrease (40.6%), with two cases of Grade 3 adverse events. Surgical procedures were performed in all 32 cases, with minor complications observed. During the follow-up period of up to 20 months, no recurrence or death were reported. Conclusions: Short-course radiotherapy combined with CAPEOX plus Envafolimab showed favorable pCR rate with manageable adverse effects and surgical complications in LARC, underscoring the potential of the combination therapy for MSS LARC. A Randomized controlled trial is warranted for further exploration and validation. Clinical trial information: NCT05216653 .
Neoadjuvant docetaxel, oxaliplatin, and S-1 plus surgery followed by adjuvant docetaxel and S-1 for patients with large type 3 or type 4 gastric cancer: Short-term outcomes of the phase II OGSG1902 trial.
Authors: Hiromichi Miyagaki, Masahiro Goto, Shunji Endo, Ryo Tanaka, Takeshi Omori, Junji Kawada, Naoki Takahashi, Toru Masuzawa, Haruna Furukawa, Yuya Sato, Takeshi Kato, Kazumasa Fujitani, Hisato Kawakami, Daisuke Sakai, Yukinori Kurokawa, Toshimasa Tsujinaka, Toshio Shimokawa, Taroh Satoh
Journal: Journal of Clinical Oncology (2024)

4031 Background: Patients with large type 3 (≥8 cm) or type 4 gastric cancer (GC) face a dismal prognosis, necessitating the development of multidisciplinary treatment, including neoadjuvant chemotherapy. We present the short-term results from the OGSG1902 (jRCTs051190060) trial, where resectable large type 3 or type 4 GC patients were treated with neoadjuvant docetaxel (DTX)/oxaliplatin (L-OHP)/S-1 (DOS) plus surgery and adjuvant DTX/S-1 (DS) therapy. Methods: Untreated large type 3 or type 4 GC patients without distant metastasis other than positive peritoneal lavage cytology (CY), aged 20-80 years, and with ECOG PS 0-1, were enrolled. Patients received three cycles of DTX (40 mg/m 2 , day1) + L-OHP (100 mg/m 2 , day1) + S-1 (80 mg/m 2 , day1-14) every 3 weeks, followed by gastrectomy with D2 lymph node dissection and 1-year DS therapy. The primary end point was the 3-year progression-free survival (PFS) rate. The secondary end points included PFS time, overall survival time, pathological response rate, response rate according to RECIST version 1.1, neoadjuvant chemotherapy completion rate, R0 resection rate, protocol completion rate, CY negative conversion rate, adverse event occurrence rate, and nutritional evaluation. Results: Forty-eight patients (pts) were enrolled from 2019 to 2022. The neoadjuvant chemotherapy completion rate was 91.7%, pathological response rate (≥Grade 1b) was 66.7%, response rate according to RECIST version1.1 for 10 pts with measurable lesions was 50.0%, CY negative conversion rate for nine CY positive pts was 88.9%, R0 resection rate was 89.6%, and the protocol completion rate was 45.8%. Adverse events (≥CTCAE Grade 3) during neoadjuvant DOS included neutropenia in 18 pts (38%), febrile neutropenia in one pt (2%), nausea in five pts (10%), diarrhea in six pts (13%), and anorexia in 18 pts (38%). Gastrectomy was performed in 47 pts [total/distal gastrectomy: 32(68%)/15(32%)]. Major postoperative complication (≥Clavien-Dindo Grade IIIa) was observed in one pt (2%), including pleural infection. Adverse events (≥CTCAE Grade 3) in 39 patients receiving adjuvant DS therapy included neutropenia in 16 pts (41%), anemia in five pts (13%), nausea in one pt (3%), diarrhea in two pts (5%), anorexia in nine pts (23%), fatigue in three pts (8%), and febrile neutropenia in four pts (10%). No treatment-related deaths were observed. Conclusions: Neoadjuvant DOS therapy for large type 3 or type 4 GC demonstrates promising efficacy with high histological response and acceptable adverse events. Future analysis of survival outcomes is planned. Clinical trial information: jRCTs051190060 .
Efficacy and safety of fruquintinib across different subgroups of patients with previously treated metastatic colorectal cancer: A meta-analysis.
Authors: Luis Felipe Leite da Silva, Renata D'Alpino Peixoto, Binbin Zheng-Lin, Junior Alonso de Menezes, Felipe Batalini
Journal: Journal of Clinical Oncology (2024)

e15589 Background: Most patients with mCRC eventually develop disease progression or intolerance to first- and second-line therapy. Fruquintinib, a selective oral tyrosine kinase inhibitor of VEGFRs 1, 2, and 3, has emerged as a novel treatment option for refractory mCRC. We conducted a meta-analysis to assess the safety and efficacy of Fruquintinib for the treatment of refractory mCRC compared to placebo in specific patient subgroups of interest. Methods: We systematically searched PubMed, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) reporting Fruquintinib efficacy. The data extraction followed PRISMA guidelines and our protocol was registered in PROSPERO (CRD42023477783). Summary hazard ratios (HRs) of overall survival (OS) and progression-free survival (PFS) were calculated using a random-effects model. The likelihood of Fruquintinib being associated with adverse events (AEs) was expressed by odds ratios (ORs). Results: Of the 1138 studies yielded by the search, three were included, totaling 1178 patients, of whom 786 (67%) received Fruquintinib. This meta-analysis of three randomized trials assessed the clinical outcomes of Fruquintinib in the intervention group compared with placebo in refractory mCRC. Pooled results from all three studies suggested the superiority of Fruquintinib in PFS (HR: 0.29 [0.25, 0.34], 95% CI, I² = 10%, p &lt; 0.01) and OS (HR: 0.66 [0.57, 0.76], 95% CI, p &lt; 0.01). Notably, subgroup analysis showed that Fruquintinib was associated with improved PFS in patients with prior use of VEGF inhibitors (HR: 0.32 [0.27, 0.38], 95% CI, p &lt; 0.01) and those with more than three prior lines of treatment (HR: 0.37 [0.25, 0.53], 95% CI, p &lt; 0.01), RAS wild-type status (HR: 0.25 [0.13, 0.35], 95% CI, p &lt; 0.01), or RAS mutated (HR: 0.33 [0.28, 0.40], 95% CI, p &lt; 0.01). In the safety analysis, fruquintinib and placebo showed no significant differences in serious AEs; nonetheless, the VEGFR inhibitor was associated with more frequent grade ≥ 3 AEs (OR: 3.13 [1.15, 8.53], 95% CI, p = 0.03). Conclusions: This meta-analysis supports the efficacy of Fruquintinib for refractory mCRC regardless of previous use of VEGF inhibitors, the number of previous treatment lines, and gene RAS mutational status, without a significant increase in serious adverse events. [Table: see text]
Cost-effectiveness of targeted vs. multi-cancer blood tests for colorectal cancer.
Authors: Reinier G.S. Meester, Andrew J. Piscitello, Lance Baldo, Noelle Griffin, William Grady
Journal: Journal of Clinical Oncology (2024)

e15526 Background: Recent research suggested that current blood tests are not cost-effective for colorectal cancer (CRC) screening in patients declining other options, i.e., compared to not screening those patients.(1) The findings were from a new decision-analytic model evaluating a multi-cancer detection (MCD) test. Relative to this MCD test, emerging “targeted” CRC blood tests have higher suggested sensitivity for CRC precursors and lower specificity for subjects without any adenomas or CRC. We examine the cost-effectiveness of these emerging tests. Methods: An established CISNET model was replicated, validated, and then used to evaluate blood testing from age 45 to age 75 years, at 1, 2 or 3-year intervals. An MCD test (Galleri®) with 99.5% specificity, 0.5% advanced adenoma (AA) sensitivity, and 82.0% CRC sensitivity (99.5%, 0.5%, 82%) was compared to two hypothetical targeted CRC tests: a low-sensitivity blood test (lsBT) just meeting U.S. national coverage criteria (90%, 10%, 74%), and a high-sensitivity blood test (hsBT) with performance assumptions based on published data (90%, 20%, 90%). Galleri costs $949 per test; lsBT and hsBT costs were varied ($100-$1500). Outcomes included the estimated mortality reduction, and the discounted quality-adjusted life-years (QALY) gained, costs of screening, follow-up colonoscopy and treatment, and costs/QALY gained vs. no screening. Results: Estimated lifetime CRC incidence and mortality without screening were 85.9 and 32.9 per 1000, respectively. Triennial screening with Galleri reduced estimated CRC mortality by 15.6%, yielded 26.9 QALYs gained per 1000, and cost $191,135/QALY gained. Annual screening increased benefit to 28.9% mortality reduction and 46.6 QALYs gained, at $300,254/QALY gained. In contrast, at $1000 per test, lsBT every 1-3 years reduced mortality by 50.2-76.4%, yielded 71.0-109.5 QALYs gained, and cost $51,330-$67,420/QALY gained. hsBT testing further improved outcomes to 60.8-80.9% mortality reduction, 88.1-119.6 QALY gained, and $35,519-$58,125/QALY gained. Costs per QALY gained were lower for lsBT and hsBT vs. Galleri irrespective of the assumed unit costs, and never exceeded $82,902 for triennial testing. Conclusions: Emerging targeted blood tests for CRC can be cost-effective for screening and could be important in reaching underserved populations, once available. Targeted tests and MCD tests differ meaningfully in their accuracy, clinical interpretation, and use, and should not be treated as a similar type of screening test.
Genetic landscape of colorectal cancer (CRC) across genetic ancestries: Implications for early cancer detection (ECD).
Authors: Alexander Ioannidis, Preethi Srinivasan, Sara L. Bristow, Shifra Krinshpun, Omid Shams Solari, Samuel Rivero-Hinojosa, Vasily N. Aushev, Adham A Jurdi, Minetta C. Liu, Bree Mitchell, Alexey Aleshin, Johannes G. Reiter, Yoshiaki Nakamura, Takayuki Yoshino, Jeffrey Wall, Parvathi Myer, Carlos D. Bustamante
Journal: Journal of Clinical Oncology (2024)

e15527 Background: Blood-based ECD has the potential to reduce mortality rates by improving strategies for adoption of and adherence to screening. As health disparities in the incidence of CRC across minority populations are known to exist, we evaluated the genomic landscape in patients with CRC across genetic ancestries. Methods: De-identified patients (N = 16,337) with stage I-IV CRC had personalized, tumor-informed commercial ctDNA testing (Signatera TM ) based on whole exome sequencing. Genetic ancestry determined via supervised local ancestry inference (pmid36042219) included African (AFR, n = 1697), Ashkenazi Jewish (ASJ, n = 1192), East Asian (EAS, n = 2247), European (EUR, n = 9726), Latino (LAT, n = 1291), and South Asian (SAS, n = 184) ancestries. Somatic driver mutations and pathogenic germline variants (PVs) in CRC-associated genes were evaluated. Somatic single nucleotide variants were used for mutational signature inference. Results: Across ancestries, 47-67% of the patients were male and most were aged &gt; 50 years. Among 35 to 50-year-olds, microsatellite instability (MSI) rates were higher in LAT (12.9%, p = 0.04) and SAS (28.3%, p &lt; 0.001) vs EUR (8.2%). Among &gt; 50-year-olds, MSI rates were lower in AFR (10.7%, p &lt; 0.001), EAS (7.9%, p &lt; 0.001), and LAT (10.4%, p &lt; 0.001) vs EUR (16.0%). The POLE signature was more common in AFR (2%, p = 0.001) vs EUR (1.1%). There were significant differences in the frequency of driver mutations and PV rates between non-EUR vs EUR ancestry groups (Table, *p &lt; 0.05, **p &lt; 0.001). Gene-level enrichment was observed in MLH1 for SAS (8.7%, p &lt; 0.001) and LAT (1.8%, p = 0.03), CHEK2 for AFR (0.4%, p = 0.03) and EAS (0.1%, p &lt; 0.001), and PMS2 (1.4%, p = 0.006) for AFR. Among patients aged ≤50 years, similar findings were observed, with differences driven by MSI rates and germline findings in Lynch syndrome (LS) genes. Conclusions: This is the first study to investigate genomic differences between multiple ancestry groups in the largest cohort to date, including EAS, LAT, and SAS populations. The differences observed between ancestries could provide insight into differences in both hereditary risk and subsequent tumor initiation and growth. Findings from this study may provide information for developing risk stratification and prevention strategies for the early detection of cancer and provide the rationale for precision treatment based on ancestry. [Table: see text]