bluuebunny/crossref_metadata_2025_split huggingface dataset:
Oncologic safety of transverse colon cancer surgery without central vessel ligation.
Authors: Lee Kyung-ha , Kim Ji Yeon , Yang In Jun , Yoon Seung-Hwan 
Published: January 2024

108 Background: Transverse colon cancers (TCC) have mixed embryological and molecular characteristics of right and left colon cancers and they are difficult to classified to right or left colon cancer due to the ambiguity of their location. Therefore, there is a lack of research about TCC alone, and it tended to be excluded in previous large clinical trials. Also, the optimal surgical procedure for each TCC varies depending on the location and stage of the tumor and anatomic structure of the patient. Consequently, standardization of surgery for TCC has not been established, and the oncologic benefits of central vessel ligation (CVL) with complete mesocolic excision and D3 dissection are unclear yet. The aim of the study is to evaluate oncologic safety of TCC surgery without CVL of middle colic artery. Methods: It is a retrospective, observational study. The clinical, surgical, and pathological characteristics were investigated retrospectively and statistical analyses were performed using chi-square test, independent samples T-test, and Kaplan-Meier analysis. Mid TCC was defined as tumor arising in the middle third of transverse colon and determined by intraoperative exploration. Hepatic and splenic flexure colon cancer, which were defined as tumor is adjacent to liver or spleen, were excluded. Radical resection was conducted along the embryological surgical plane, following D2 or D3 dissection. Central vessel ligation was defined as ligation of root of middle colic artery. Results: The numbers of proximal, mid, and distal TCC were 48 (45.3%), 32 (30.2%), and 26 (24.5%), respectively. The numbers of right hemicolectomy, transverse colectomy and left hemicolectomy were 57 (53.8%), 28 (26.4%) and 21 (19.8%). The numbers of No CVL group and CVL group were 47 (44.3%) and 59 (55.7%). The numbers of stage I, II and III were 24 (22.6%), 45 (42.5%), 37 (34.9%), and 49 patients underwent adjuvant treatment. The most frequent organ of recurrence was peritoneum (N=6, 5.6%). There was no statistically significant difference of stage, mean number of retrieved lymph node (24.12 vs. 22.36 p=0.464), mean number of metastatic lymph node (1.53 vs. 0.74, p=0.163), mean proximal margin (19.2 cm vs. 16.7 cm, p=0.139), mean distal margin (9.6 cm vs. 9.9 cm, p=0.753), adjuvant chemotherapy, and the rate of recurrence with lymph node metastasis. Also, there was no statistically significant difference of 6-year DFS survival and OS in stage II and III. Conclusions: When following oncologic plane and adequate lymph node dissection, resection without CVL for TCC is considered to have equal surgical and oncologic outcomes comparing to resection with CVL. Therefore, it is considered that CVL would not be always mandatory for TCC surgery, and a branch of middle colic artery could be preserved, if necessary.
A first-in-human, open-label, phase I trial of daily oral zelenirstat, an NMT inhibitor, in patients with relapsed/refractory advanced cancer including gastrointestinal cancers.
Authors: Spratlin Jennifer L. , Sangha Randeep S. , Jamal Rahima , Beauchamp Erwan , Berthiaume Luc G. , Mackey John Robert 
Published: January 2024

129 Background: Myristoylation catalyzed by N-myristoyltransferases (NMT) 1 and 2 regulates membrane-bound signaling important in cancer, including Src and Src-family tyrosine kinases. Zelenirstat is a potent oral small molecule pan-NMT inhibitor. Transcriptomic analysis of zelenirstat treated cell lines identified an expression signature that predicts cancers most likely to be responsive to NMT inhibition; high sensitivity scores were seen in colorectal carcinomas and diffuse large B-cell lymphoma. The objectives of this phase I study were to determine the safety, tolerability, and maximum tolerated dose (MTD) of zelenirstat monotherapy in patients (pts) with refractory cancers. Methods: Pts with advanced solid malignancies or relapsed/refractory B-cell lymphomas were dose escalated with daily oral zelenirstat in 28-day cycles until progressive disease or dose-limiting toxicity (DLT). Results: Between September 2021 and July 2023, pts received 28-day cycles of zelenirstat ranging from 20 mg/d to 280 mg/d. In 21 evaluable patients, DLT was not observed up to and including the 210 mg/d cohort. Gastrointestinal DLTs were seen in the 280 mg/d cohort, establishing 210 mg/d to be the MTD. In doses up to and including 210 mg/d, gastrointestinal adverse events were the most common, reported in 29% of pts; these were primarily Gr 1 or 2 diarrhea, nausea or vomiting. Transient Gr 2 thrombocytopenia was seen in 3 pts. Zelenirstat did not induce neuropathy, alopecia, or prolong QT intervals. Plasma concentrations peaked between 1h and 4 h, terminal half-lives were 6.7 to 12 h, and steady state was achieved by day 8. Proton pump inhibitors lowered exposure and were prohibited in the higher dose cohorts. At 100 mg/d and higher, trough plasma concentrations exceeded the levels predicted to be therapeutic. Stable disease as best response was seen in 5 (30%) of 17 evaluable pts, including 1 patient with advanced refractory colon cancer who received 6 cycles of therapy at 140 mg daily dosing prior to PD. Another colon cancer patient with 5 prior lines of therapy continues 210 mg/d dosing after > 5 cycles of therapy, with non-RECIST criteria reductions of approximately 50% in CEA and tumor volumes. Conclusions: Zelenirstat was well-tolerated on a continuous daily oral schedule at doses as high as 210 mg/d, establishing the MTD to be 210 mg. The absence of severe toxicities, attainment of plasma concentrations highly active in preclinical models, and early evidence of clinical benefit in patients with refractory colon cancer warrant further trials. Updated data will be presented. Clinical trial information: NCT04836195 .
Fruquintinib with PD-1 inhibitors versus fruquintinib monotherapy in late-line mCRC: A retrospective cohort study based on propensity score matching.
Authors: An Tianqi , Lian Yugui , Zhou Quanbo , Zhao Chao , Wang Zheng , Zhao Ruihua 
Published: January 2024

139 Background: Immune checkpoint inhibitors (ICIs) are highly effective in patients with microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) metastatic colorectal cancer (mCRC). However, the population of MSI-H/dMMR only accounts for 5% of mCRC. And most of the remaining microsatellite stable or proficient mismatch repair (MSS/pMMR) mCRC patients appeared not to benefit from mere immunotherapy. Fruquintinib, as the standard third-line regimen for mCRC, is an oral small-molecule anti-angiogenic tyrosine kinase inhibitor. Studies demonstrated that fruquintinib combined with programmed death receptor-1 (PD-1) inhibitors (FP) can reverse the immunosuppression and achieve promising efficacy. However, due to the lack of the research comparing the efficacy between fruquintinib monotherapy (FM) and FP, it remains unclear if FP can bring extra benefit. Methods: This is a retrospective cohort study conducted in the First Affiliated Hospital of Zhengzhou University. Patients (pts) with MSS/pMMR mCRC who had received at least the 2nd line treatment were eligible. Propensity score (PS) would be calculated to balance the baseline characteristics of two cohorts. Progression-Free survival (PFS) was set as the primary endpoint. The Kaplan–Meier method and Cox proportional hazard model was used to evaluate PFS and to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results: From Apr 2020 to Jan 2023, 83 eligible pts in total were enrolled. According to the treatment received, 47 and 36 pts were respectively allocated into FP cohort and FM cohort. With a global median follow-up of 16.5 mo, the crude PFS was 6.8 (95% CI: 4.3-11.3) mo in FP cohort vs. 3.9 (3.1-4.7) mo in FM cohort. The HR of FP was 0.58 (95% CI: 0.34-0.98, FM as reference). Multivariate Cox regression showed that the adjusted HR was 0.49 (95% CI: 0.26-0.93), which was adjusted with sex, age greater than 65 yr, ECOG-PS, RAS mutation, BRAF mutation, location of lesion (left or right), surgery history, metastases (liver and lung), prior medication (bevacizumab and cetuximab), and current line (3 or later). With PS, we performed three statistical methods, namely inverse probability weighting, PS matching (the sample size was 37 vs. 29 after matching), and additional adjustment for propensity score with multivariate cox regression. The HR of FP were 0.49 (95% CI: 0.26-0.94), 0.40 (95% CI: 0.21-0.77), and 0.46 (95% CI: 0.24-0.90), respectively. Conclusions: Pts in FP cohort showed a significantly greater PFS than those in FM cohort. And with further analysis, FP indicated robustly lower HRs than FM. Our study suggests FP could provide additional benefits to pts with MSS/pMMR mCRC, and warrants further investigations in a large cohort.
Tumor genomics and sidedness to predict outcomes in metastatic colorectal cancer (mCRC).
Authors: Boland Patrick M , Quintanilha Julia , Li Gerald , Clark Allison , Carlson Erik , Morley Samantha , Aboosaiedi Ali , Mitchell Jerry W. , Ross Jeffrey S. , Graf Ryon , Deming Dustin A. , Lieu Christopher Hanyoung 
Published: January 2024

207 Background: Tumor sidedness is a prognostic factor and predictive parameter for EGFR monoclonal antibody (mAb) treatment in mCRC. Sidedness is believed to be a surrogate for genomic differences. This study aimed to evaluate genomics vs. tumor sidedness in anticipating outcomes in mCRC. Methods: We included patients (pts) with microsatellite stable mCRC tested by Foundation Medicine tissue comprehensive genomic profiling assay. Patient data was obtained by the US-based de-identified Flatiron Health-Foundation Medicine real-world clinico-genomic database (FH-FMI CGDB), originating from approximately 280 US cancer clinics (1/2011–3/2023). Genomic alterations (GA) in 324 genes were compared between right and left side tumors using Fisher’s exact test, adjusted for multiple comparisons. Real-world progression-free survival (rwPFS) and overall survival (rwOS) were compared by Cox proportional hazard models adjusted for prognostic features in pts receiving 1st line chemotherapy (chemo) + EGFR mAb or bevacizumab (bev). Multivariable analyses including prognostic features, sidedness and GA were performed. Comparisons of the explanatory power of genomics vs. sidedness were performed by the likelihood ratio test (LRT). Results: 3845mCRC pts (2584 left and 1261 right) were included. GA in APC, TP53, ARID1A, and FBXW7 were more prevalent in left side, while GA in BRAF, KRAS, AMER1A, PIK3CA, RNF43, BCOR, PTEN, SMAD4, MAP2K1, and BCOR in right side. 2109 pts received chemo + EGFR mAb or bev. Multivariable analyses identified BRAF, KRAS, MAP2K1, and APC as independently associated with outcomes. Pts were classified as having GA in RAS pathway (RASalt: KRAS/NRAS, BRAF, or MAP2K1), APC (APCalt), both RAS pathway and APC (APC/RASalt), and none. RASalt group had less favorable outcomes while APCalt group had more favorable outcomes, regardless of treatment received and sidedness. LRT indicated that when genomics was added to the sidedness evaluation, there was an improvement in outcome prediction (p<0.001), but not when sidedness was added to genomics. Conclusions: Tumor genomics better explains differences in outcomes than sidedness in 1st line treatment in mCRC. [Table: see text]
Association of circulating tumor DNA (ctDNA) molecular disease (MRD) detection with lymph node metastasis after local excision of pathological T1 colorectal cancer: First results from DENEB, a CIRCULATE-Japan GALAXY substudy.
Authors: Miyo Masaaki , Kato Takeshi , Nakamura Yoshiaki , Mishima Saori , Bando Hideaki , Yukami Hiroki , Ando Koji , Watanabe Jun , Akazawa Naoya , Yokota Mitsuru , Kagawa Yoshinori , Jurdi Adham A , Liu Minetta C. , Oba Koji , Taniguchi Hiroya , Kotani Daisuke , Oki Eiji , Takemasa Ichiro , Mori Masaki , Yoshino Takayuki 
Published: January 2024

23 Background: Patients with pathological T1 (pT1) colorectal cancer (CRC) at high risk for lymph node metastasis (LNM) after complete local resection are recommended to receive additional intestinal resection along with lymph node dissection. However, the existing pathological criteria for risk stratification of LNM are inadequate, such that ~90% of patients without LNM are exposed to potentially unnecessary treatment. Based on the CIRCULATE-Japan platform, we launched DENEB, a new prospective substudy within the GALAXY observational study, to explore the ability of predicting LNM using circulating tumor DNA (ctDNA) detection compared to the standard pathological criteria. Methods: This study included patients with pT1 CRC who underwent complete local resection and were scheduled for additional intestinal resection with lymph node dissection based on the standard pathologic risk-stratification criteria for LNM. The additional surgery was indicated for patients meeting any of the following criteria: (1) depth of submucosal invasion (>1000µm); (2) lymphovascular invasion; (3) poorly differentiated adenocarcinoma, signet-ring cell carcinoma, or mucinous carcinoma; and (4) high-grade tumor budding (BD2/3) at the site of deepest invasion according to the Japanese guideline. ctDNA was analyzed from plasma samples collected within 4 weeks before the additional intestinal resection using a personalized, tumor-informed assay (Signatera bespoke multiplex-PCR NGS assay). The study assessed the diagnostic concordance rate between ctDNA detection and the occurrence of LNM. Results: Of 208 CRC patients enrolled between July 2021 and May 2023 in DENEB, 166 patients met the inclusion criteria. Of these, 22 (13.3%) were ultimately diagnosed with pStage III due to the presence of LNM in additional intestinal resection. Among the 166 patients, 6 patients tested ctDNA-positive; all 6 had LNM, yielding a positive predictive value of 100.0%. On the other hand, 160 patients had ctDNA-negative results, 144 of whom did not have LNM, resulting in a negative predictive value of 90.0%. The overall diagnostic concordance rate for ctDNA in detecting LNM was 90.4% (95% confidence interval, 84.8% to 94.4%). All 6 patients with a ctDNA-positive result and LNM had left-sided colorectal cancer and a tumor diameter greater than 13 mm. Conclusions: This analysis showed that ctDNA testing has the potential to improve risk stratification of LNM in patients with pT1 CRC who underwent complete local resection. Clinical trial information: UMIN000039205 .
SKYSCRAPER-08: A phase III, randomized, double-blind, placebo-controlled study of first-line (1L) tiragolumab (tira) + atezolizumab (atezo) and chemotherapy (CT) in patients (pts) with esophageal squamous cell carcinoma (ESCC).
Authors: Hsu Chih-Hung , Lu Zhihao , Gao Shegan , Wang Jun-Ye , Sun Jong-Mu , Liu Tianshu , Fan Qingxia , Cai Jun , Ge Feijiao , Li Sijing , Zhang Li , Cha Edward , Shen Lin 
Published: January 2024

245 Background: Inhibition of TIGIT, a novel checkpoint inhibitor, may further amplify immune responses by complementing the PD-L1/PD-1 pathway. Anti-tumor activity has been demonstrated with cancer immunotherapy in ESCC. SKYSCRAPER-08 (NCT04540211) is evaluating the efficacy and safety of tira (anti-TIGIT) + atezo (anti-PD-L1) in combination with CT compared with placebo + CT as 1L treatment (tx) in an Asian population with unresectable locally advanced (LA), unresectable recurrent, or metastatic (R/M) ESCC. Methods: Eligible pts (confirmed LA or R/M ESCC; ECOG PS 0–1; no prior systemic tx) were randomized 1:1 to receive tira 600mg + atezo 1200mg + CT (paclitaxel 175mg/m2 + cisplatin 60–80mg/m2, local standard of care) or placebo + CT on Day 1 of each 21-day cycle (cycles 1–6); followed by tira + atezo or placebo maintenance until loss of clinical benefit/unacceptable toxicity. Primary endpoints: independent review facility (IRF)-assessed progression-free survival (PFS) and overall survival (OS). Secondary endpoints: investigator (INV)-assessed PFS, objective response rate (ORR), duration of response (DoR), and safety. Results: Overall, 461 pts were randomized (tira + atezo + CT, n= 229; placebo + CT, n=232). Pt characteristics were generally balanced between arms. As of 15 June 2022 (minimum survival follow-up 6.5 months [mo]; PFS primary analysis), median IRF-assessed PFS was 6.2 mo for tira + atezo + CT vs 5.4 mo for placebo + CT (HR 0.56; 95% CI: 0.45, 0.70; P<0.0001). As of 13 Feb 2023 (minimum survival follow-up 14.5 mo; OS final analysis), median OS was 15.7 mo for tira + atezo + CT vs 11.1 mo for placebo + CT (HR: 0.70; 95% CI: 0.55, 0.88; P= 0.0024). INV-assessed PFS, IRF-assessed ORR and DoR are presented in Table. Treatment-related adverse events (TRAEs) occurred in 98.2% of pts (both arms); Grade 3/4 TRAEs in 59.6% (tira + atezo + CT) and 56.4% (placebo + CT) of pts; Grade 5 TRAEs in 2.6% (tira + atezo + CT) and 0.9% (placebo + CT) of pts. Conclusions: The study met both primary endpoints of IRF-assessed PFS and OS, demonstrating statistically significant and clinically meaningful improvements in PFS and OS for tira + atezo + CT over placebo + CT. Generally consistent benefit was observed across subgroups, including PD-L1 status. The safety profile was consistent with the known risks of the individual tx. Clinical trial information: NCT04540211 . [Table: see text]
Prevalence of modifiable risk factors of Hispanic adult patients admitted with gastric cancer in the US.
Authors: Nieto Dominguez Alejandro , Eichinger Sarah Elizabeth , Guifarro Rivera Daniel 
Published: January 2024

254 Background: More than 19% of the US population is comprised of Hispanic individuals. For decades, cancer incidence has been increasing in this population, including cancers associated with infection (gastric, hepatic, cervical) and resulting from delayed screening (colorectal, cervical and breast). Risk factors associated with gastric cancer include H. pylori, obesity, alcohol, and tobacco use. However, ethnicity has not been a commonly reported risk factor despite the fact that studies have shown increasing incidence of gastric cancer in Hispanics at a younger age. Methods: We used the 2016-2019 National Inpatient Sample (NIS) database to stratify patients with gastric cancer by age, ethnicity, and comorbidities. Results: There were 77,745 adults with gastric cancer. Of these, 578 (7.45%) were ages 18-44 (group 1), 28,370 (36.47%) 45-64 years old (group 2), and 43,590 (55.08%) were over 65 (group 3). Group 1 was comprised of 29.4% White, 34.3% Hispanic, 14.5% Black, and 21.8% Asian or Pacific Islander patients. Group 2 consisted of 46.7% White, 19.7% Hispanic, 17.4% Black, and 16.2% Asian or Pacific Islander individuals. Group 3 had the highest percentage of White patients (56.0%) and lowest percentage of Hispanic individuals (12.9%). Group 3 also consisted of 15.1% Black and 16.0% Asian or Pacific Islander patients. In Hispanics with gastric cancer, there was a predominance of H. pylori among younger patients (8.6% in group 1 vs 3.6% and 2.1% in groups 2 and 3 respectively) (p = 0.00). Incidence of smoking increased with age (19.9% in group 1, 28.1% in group 2 and 31.1% in group 3) (p = 0.00) as did incidence of diabetes (8.1% in group 1, 26.4% in group 2 and 36.0% in group 3) (p = 0.00). Alcohol use was 3.0% in group 1, 4.3% in group 2 and 2.3% in group 3 (p = 0.035). The differences between all groups for gastric ulcer, gastric polyp and obesity were not statistically significant. Conclusions: Gastric cancer accounts for approximately 1.5% of all new cancers diagnosed in the US, with a high incidence in older White populations. However, this study demonstrates that there is a large proportion of young Hispanics with gastric cancer who have higher associated instances of H. pylori. This suggests the need for further research to determine if there is utility in screening for H. pylori in asymptomatic young Hispanics to decrease the burden of gastric cancer in this population. [Table: see text]
Esophageal cancer in Hispanics: A propensity score matched analysis of the National Cancer Database.
Authors: Meredith Kenneth Lee , Huston Jamie , Shridhar Ravi 
Published: January 2024

258 Background: Hispanics are the fastest-growing minority and largest ethnic group accounting for 19.1% of the US population. The American Cancer Society estimated 21,560 new cases of esophageal cancer (EC) in the US in 2023. Hispanics are reported to be at high risks for EC. We sought to interrogate the demographic patterns of esophageal cancer in Hispanics. Additionally, we sought to examine evidence of socioeconomic disparities and differential therapy. Methods: We identified Hispanic vs Non-Hispanic (NH) patients in the National Cancer Database with esophageal cancer between 2005–2018. Variables compared were age, sex, tumor data, surgical intervention, type of treatment, insurance status, income, residence area, and Charlson/Deyo score. Pearson’s Chi-square test was used to compare categorical variables. Groups were statically equated with propensity score-matched analysis (PSM). Survival analysis was estimated by the Kaplan-Meier method and associated log-rank test. Significance was considered at p-value ≤0.05. Results: We identified 66,335 patients with a median age of 63 years (18-90). Hispanics represented 4.2% (2,786) of the entire patient cohort. In this US population we identified significant disparities between Hispanic and NH groups. Differences among Hispanics included higher prevalence of squamous EC (22% vs 19%) p<0.001, higher likelihood of stage IV disease (40.7% vs. 34.8%) p<0.001, younger age p<0.001, higher uninsured status (10.3% vs 3.3%) with income < $40,227 (27.5% vs 16.9%) p<0.001 when compared to NH. However, Hispanics were less likely to have surgical intervention (20.5% vs 27.5%) p<0.001, receive neoadjuvant therapy (61.8% vs 72%) and overall, less likely to receive any type of treatment (30.1% vs 26.1%) when compared to NH p<0.001. Time to treatment was delayed in those Hispanics who were uninsured 37 weeks (22-55) compared to those with private insurance 31 weeks (20-47) p<0.001. Multivariate analysis revealed that any treatment, insurance status, and lower income were all predictors of survival. Treated Hispanics demonstrated no difference in survival then their treated non-Hispanic counterparts (median survival 18.5 vs 18.7 months) with overall 5 year survival at 24% and 25% respectively (p=0.66). Conclusions: Despite lower prevalence, there is a disproportionately higher number of metastatic and untreated cases of esophageal cancer among Hispanics. This disparity may be explained by Hispanics' limited access to medical care exacerbated by their socioeconomic and insurance status. Our findings warrant further clinical and epidemiologic research to reveal other factors impacting these health and health care disparities.