tbuckley/cabot-search huggingface dataset:
Disparities in organ preservation rate for high-risk stage I rectal cancer.
Authors: Annmarie Butare, Michael Honaker
Journal: Journal of Clinical Oncology (2025)

37 Background: Guidelines for the treatment of high-risk stage I rectal cancer is a curative oncologic resection, while recommendations for stage II/III rectal cancer include neoadjuvant therapy with the option for organ preservation. The paradoxical nature of treating less advanced stage cancer with more morbid surgery calls into question the use of organ preservation strategies (OP) for less advanced disease. While sphincter preservation is appealing, benefits from OP require commitment to preoperative therapy, which may require more significant time and financial commitments than a single-stage curative treatment. This study aims to evaluate disparities in social determinants of health regarding receipt of OP compared to major oncologic resection for high-risk stage I rectal cancer. Methods: The National Cancer Database was queried to analyze all patients with high-risk stage 1 rectal cancer between 2004-2021. High-risk stage 1 disease was defined as either T2 or T1 tumors with lymphovascular invasion, or grade 3 or 4 differentiation. Covariates in patients who underwent OP, defined as chemoradiation therapy without oncologic resection or local excision, were compared to those who underwent major oncologic resection. Additional variables included age, sex, race, great circle distance, insurance status, education, facility type, income, rurality, and comorbidity index. Univariate and multivariate analyses were utilized to compare association of covariates to OP. Results: Of the 63,762 patients included, 9,261 (14.5%) underwent OP. Increased rates of OP were seen with increasing age (OR 1.029, p&lt;0.0001), female sex (OR 1.147, p&lt;0.0001), higher education level (OR 1.179, p=0.0034), rurality (OR 1.273, p=0.0003) and lower income (OR 0.757 for income &gt;74K, p &lt;0.0001). Interestingly, OP was more frequently utilized at community cancer centers in comparison to comprehensive cancer centers (OR 0.78, p&lt;0.0001) and academic centers (OR 0.842, p=0.0021). Race, insurance status, distance to treatment, and comorbidity index were not statistically significant predictors of OP. Of note, those who underwent OP had a considerable delay in time to first treatment, with median time to treatment of 36 days in comparison to 13 days for oncologic resection. Conclusions: Socioeconomic and demographic variables are associated with receipt of OP. While plausible that a treatment strategy that requires frequent office visits, travel expenses, and time off from work may preclude OP, lower income and rurality had increased odds of OP. Future aims should be directed to identifying root causes of disparities in treatment and their clinical consequences.
Effect of SHR-1701 on chemotherapy (chemo)-induced myelosuppression: Data from a phase 3 study in HER2-negative gastric/gastroesophageal junction adenocarcinoma (G/GEJA).
Authors: Zhi Peng, Jufeng Wang, Yanqiao Zhang, Hongli Li, Qun Zhao, Xiaodong Zhu, Shaozhong Wei, Ying Cheng, Kangsheng Gu, Jun Bai, Yigui Chen, Zhongtao Zhang, Jun Zhang, Junsheng Wang, Zuoxing Niu, Yueyin Pan, Zhigao Wang, Wenliang Wang, Hongxia Han, Lin Shen
Journal: Journal of Clinical Oncology (2025)

335 Background: Blocking TGF-β signaling has the potential to facilitate the recovery from chemo-induced myelosuppression. SHR-1701 is a bifunctional agent targeting PD-L1 and TGF-β. Methods: In the multicenter, randomized, double-blind phase 3 study (NCT04950322), SHR-1701 plus CAPOX demonstrated a statistically significant and clinically meaningful benefit in OS compared with placebo plus CAPOX in patients (pts) with previously untreated, unresectable locally advanced or metastatic HER2-negative G/GEJA (ESMO 2024, LBA60). Here, we reported the effect of SHR-1701 on chemo-associated myelosuppression. Results: In total, 364 and 366 pts in the SHR-1701 and placebo arm received assigned treatment. As of May 20, 2024, with a KM estimated median follow-up of 13.6 mo, all study medications showed similar exposure duration between the two arms (Table). Occurrence of treatment-related adverse events was generally comparable (any grade, 97.8% in SHR-1701 arm vs 98.4% in placebo arm; grade ≥3, 62.6% vs 59.0%). SHR-1701 reduced the incidence of any grade decreased platelet count, decreased neutrophil count, and decreased white blood cell count by 8.7%, 10.1%, and 11.2%, and for grade ≥3, by 9.1%, 4.3%, and 1.6%, respectively (Table). Compared with the placebo arm, less pts in the SHR-1701 arm used platelet growth factors (30.2% vs 42.9%) and white blood cell growth factors (32.7% vs 39.6%). Conclusions: SHR-1701 showed the capacity to suppress chemo-associated myelosuppression. Clinical trial information: NCT04950322 . Safety. SHR-1701 plus CAPOX(N=364) Placebo plus CAPOX(N=366) Treatment difference (SHR-1701 vs placebo) Treatment exposure (day), median (IQR) SHR-1701/placebo 137.0 (65.5-251.5) 127.5 (62.0-190.0) NA Capecitabine 122.0 (83.0-138.0) 122.0 (73.5-135.0) NA Oxaliplatin 107.0 (66.0-123.0) 108.5 (64.0-121.0) NA Treatment-related hematological toxicities, n (%) or % Any grade Grade ≥ 3 Any grade Grade ≥ 3 Any grade Grade ≥ 3 Platelet count decreased 217 (59.6%) 69 (19.0%) 250 (68.3%) 103 (28.1%) -8.7% -9.1% Neutrophil count decreased 163 (44.8%) 44 (12.1%) 201 (54.9%) 60 (16.4%) -10.1% -4.3% White blood cell count decreased 147 (40.4%) 13 (3.6%) 189 (51.6%) 19 (5.2%) -11.2% -1.6%
Racial disparities in cancer stage at diagnosis among older adults with gastrointestinal cancers in the southeastern United States.
Authors: Apoorva Doshi, Grant Richard Williams, Smith Giri
Journal: Journal of Clinical Oncology (2025)

806 Background: Prior studies have documented racial disparities in survival among older adults with various gastrointestinal (GI) cancers, but mechanisms remain poorly understood. We hypothesized that delayed diagnosis leading to advanced cancer stage at presentation could be a contributing factor to these disparities. Methods: We included adults ≥ 60 years with newly diagnosed GI cancers presenting for initial consultation at University of Alabama at Birmingham from October 2017 to April 2024. Using self-reported race and ethnicity, we stratified patients into Non-Hispanic Whites, Non-Hispanic Black, Hispanics and other category. For this analysis, we limited our cohort to the first two categories. Cancer stage was abstracted from the Electronic Health Record and followed American Joint Commission on Staging (AJCC) 7 th manual. We performed two-sided Pearson’s chi square test to test the association between stage at diagnosis and race. We performed this analysis for the overall cohort as well as for specific GI cancer types. The level of significance was set at p &lt; 0.05. Results: A total of 1714 patients were included; Out of which 74% were non non-Hispanic white and 26% were African American. The median age at presentation was 68 years (interquartile range: 64 - 74), and 42% were females. The most common cancer type was colorectal (28%) followed by pancreatic (26%), hepatobiliary (22%), other GI cancers (14%) and gastroesophageal (10%). Overall, around 45% patients had Stage IV at diagnosis, followed by Stage III (26%), Stage II (17%) and Stage I (11%). We found that as compared to non-Hispanic Whites, non-Hispanic Blacks were more likely to have advanced stage disease, stage III (29% vs 25%) and stage IV (47% vs 45%), this association was statistically significant (Table). Furthermore, this association was most prominent for pancreatic cancers, where non-Hispanic Blacks were more likely to have advanced stage disease, stage III (21% vs 16%), and stage IV (50% vs 47%; p &lt; 0.05). Conclusions: We report that among older adults with GI cancers, African Americans were more likely to have advanced stage at diagnosis compared to non-Hispanic whites, specifically in patients with pancreatic cancer. This finding may contribute to some of the racial disparities observed in survival outcomes in this population. Contingency table showing frequencies (%) of cancer stages for non-Hispanic Whites and African Americans. GI Cancer Stage Non-Hispanic White African American p value Stage I 138 (11%) 51 (11%) &lt;0.05 Stage II 236 (19%) 57 (13%) Stage III 321 (25%) 129 (29%) Stage IV 572 (45%) 210 (47%)
PD-1 inhibitor (sintilimab) and fruquintinib plus SOX as conversion therapy for initially unresectable gastric/gastroesophageal junction adenocarcinoma (GC/GEJC): Updated results from a single-arm, phase 2 clinical trial.
Authors: Fei Ma, Suxia Luo, Bin Zhang, Qi Ma, Sheqing Ji, Zhandong Zhang, Yonglei Zhang, Wei Yang, Liangqun Peng, Dandan Guo, Jinjun Ren, Yuan Zhang, Yueyue Su, Jing Li, Wentao Liu, Jinxi Huang, Weiwei Yuan
Journal: Journal of Clinical Oncology (2025)

406 Background: The evidence of conversion therapy for unresectable GC/GEJC is limited. Previously, preliminary results of the ongoing open-label, phase 2 study (NCT05177068) have showed promising R0 surgical conversion rate (62.1%), R0 resection rate (100%) and acceptable tolerability in unresectable GC/GEJC with sintilimab and fruquintinib plus SOX (ASCO 2024). Here we present updated results with longer follow-up duration, including more enrolled patients. Methods: Eligible patients were administered fruquintinib (4mg/d, po, qd, d1-14), sintilimab (200mg, iv, d1), oxaliplatin (130 mg/m 2 , iv, d1) and S-1 (40-60mg based on BSA, po, bid, d1-14) every 3 weeks for 3 or 6 cycles. One more cycle of sintilimab plus SOX was given before resection. Patients were assessed for tumor response and surgical feasibility by radiologic imaging &amp; MDT every 3 cycles. Primary endpoint was R0 resection rate. Secondary endpoints included pathological response, ORR, PFS, OS, and safety. Results: As of July 30, 2024, 42 pts (37 males/5 females) with a median age of 64 years (range: 43–76), 71% ECOG PS1, 55% GEJC were enrolled. Nine (21.4%) of the 42 pts had distant metastasis and five (11.9%) pts had more than one unresectable factors. The most common unresectable factors were extensive or bulky lymph nodes 54.8% (23), liver metastasis 11.9% (5), peritoneal metastasis 4.8% (2), para-aortic lymph node metastasis 2.4% (1), and local progression 38.1% (16). Of 35 evaluable pts, ORR was 68.6% and DCR was 97.1%. Among the 29 pts who had completed surgical conversion, the R0 resection rate was 100% (29/29) and R0 surgical conversion rate was 82.9% (29/35). 10.3% (3/29) pts achieved pathological complete response (pCR), and 20.7% (6/29) pts reached tumor regression grade (TRG) 0-1. Additionally, the pathological response rate (pRR) according to JCGC (≥ Grade 1b) was 93.1% (27/29). Seven pts (16.7%) had grade 3 treatment-emergent adverse events, including 4 cases of anemia, 2 cases of neutrophil count decreased, and 1 case of each (lymphocyte count decreased, gastrointestinal hemorrhage, diarrhea, and immune-related pneumonitis). No severe surgery-related complication was observed. Conclusions: Fruquintinib combined with sintilimab and SOX yielded very high R0 conversion rate and R0 resection rate with a manageable safety profile in unresectable GC/GEJC, representing a potential and feasible conversion therapy regimen for this population. Survival data will continue to be followed up. Clinical trial information: NCT05177068 .
What is the optimal treatment strategy of salvage line treatment after progression on anti-epidermal growth factor receptor monoclonal antibody in patients with tissue <i>RAS/BRAF</i> wild-type metastatic colorectal cancer?
Authors: Emiko Tange, Hiroki Osumi, Keitaro Shimozaki, Koichiro Yoshino, Mikako Tamba, Shohei Udagawa, Shota Fukuoka, Mariko Ogura, Takeru Wakatsuki, Akira Ooki, Keisho Chin, Kensei Yamaguchi, Eiji Shinozaki
Journal: Journal of Clinical Oncology (2025)

138 Background: Trifluridine/tipiracil (FTD/TPI) plus bevacizumab (BEV) and anti-epidermal growth factor receptor (EGFR) monoclonal antibody (mAb) re-challenge are treatment options for tissue RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC) in salvage line, although the optimal treatment sequence of salvage line remains unclear. Methods: RAS/BRAF WT mCRC patients refractory to anti-EGFR mAb were retrospectively enrolled at a single cancer institute from November 2017 to April 2024. We compared responses, progression-free survival (PFS), and overall survival (OS) between Group A (anti-EGFR mAb re-challenge given first) and B (FTD/TPI plus BEV given first). We compared responses between Group C (treated with anti-EGFR mAb re-challenge at any line) and D (treated with FTD/TPI plus BEV at any line). We explored the clinical factors related to the treatment efficacy using multivariate analysis. Results: A total of 89 patients (median age, 63 years) were included. The cohort included 74 patients with a primary lesion in the left-sided colon, while 15 patients had a primary lesion in the right-sided colon. The response rate (RR) was 3.4%. The disease control rate (DCR) was 52.8%. The median PFS (mPFS) and OS (mOS) were 3.5 months (95% confidence interval [CI], 2.8-4.2) and 12.8 months (95% CI, 8.8-15.7) respectively. Two of 18 patients (11.1%) in Group A and 1 of 71 patients (1.4%) in Group B achieved partial response (PR). The RR of Group C was significantly higher than Group D (9.6% vs 1.2%; p = 0.031). Both PFS and OS showed no significant difference between Group A and B (mPFS: 3.3 vs 3.9 months; hazard ratio [HR], 1.08; 95% CI, 0.63-1.84; p = 0.79) (mOS: 12.8 vs 15.0 months; HR, 0.90; 95% CI, 0.49-1.65; p = 0.72). Multivariate analysis identified that primary tumor resection was associated with PFS (HR, 0.44; 95% CI, 0.25–0.80; p = 0.0068) and primary tumor resection (HR, 0.34; 95% CI, 0.18–0.65; p = 0.0010) and serum CA19-9 level (HR, 1.75; 95% CI, 1.02-3.00; p = 0.043) were associated with OS. Conclusions: No significant survival difference was observed between patients administered anti-EGFR mAb re-challenge first and those administered FTD/TPI plus BEV first, whereas the RR of anti-EGFR mAb re-challenge is significantly higher than that of FTD/TPI plus BEV.
KRAS status in lung oligometastases treated with SBRT.
Authors: Mauro Loi, Marianna Valzano, Michele Aquilano, Ilaria Morelli, Giulio Frosini, Gabriele Simontacchi, Pierluigi Bonomo, Alessandra Galardi, Viola Salvestrini, Carlotta Becherini, Lorenzo Livi
Journal: Journal of Clinical Oncology (2025)

264 Background: Stereotactic Body Radiotherapy (SBRT) to lung metastases (LM) from colorectal cancer (CRC) has been applied to improve disease control in in the oligometastatic (OM) and oligoprogressive (OP) setting. The aim of this study is to assess the impact of KRAS mutational (KRASmut) status in the response to SBRT in LM. Methods: Data from a consecutive cohort of OM/OP CRC patients treated at our Institution with SBRT for LM from May 2019 to March 2024 were retrospectively reviewed. Patients (age, KRASmut in primary tumor, OM/OP disease, chemotherapy lines prior to SBRT) and treatment-related variables (dose regimen and Biologically Effective Dose: BED, toxicity) were collected. Local Control (LC) was defined as time from SBRT to local failure or last radiologic follow-up. Results: Sixty-two patients (median age: 74 years, range 49-85), accounting for 103 LM were included. LM were treated in the OM and OP setting in 65(63%) and 38(37%) cases, respectively. SBRT was delivered before chemotherapy (n=49,48%) or following first (n=31,30%) or further chemotherapy lines (n=23,22%). KRASmut was present ab initio in 49% of cases (n=50). Dose regimens included 48-60 Gy in 3-8 fractions, resulting in a median BED of 115.5 (range 76.8-151.2) Gy 10 : a BED&gt;100Gy 10 was delivered in 92% (n=95) of treatment courses. Median follow-up was 16 (range 2-45) months. Median LC was not reached; 1- and 3 years LC rates were 85% and 67% respectively. At multivariate analysis (MVA), only a BED≤100Gy 10 (p=0.029, HR 2.99, IC95% 1.1- 9.5) and prior second or further chemotherapy line (p=0.031, HR 3.2, IC95% 1.1- 8.1) were independently correlated with impaired LC. No grade &gt;2 toxicity was observed. Focusing on patients receiving no chemotherapy or first-line treatment before SBRT, 1- and 3 years LC rates were 92% and 77% respectively (median: NR). At MVA, while BED≤100Gy 10 (p=0.036, HR 6.96, IC95% 1.9-25.7) was associated with poorer LC, lack of KRASmut (p=0.037, HR 0.26, IC95% 0.07- 0.9) was independently correlated with improved LC. Conclusions: SBRT in LM from OM/OP CRC results in high LC rates, particularly with intensive regimens in non-heavily pretreated patients. No impact of KRASmut was observed. Due to possible occurrence of secondary mutations in the pretreated population, a subset analysis in the chemotherapy-naive/first-line subset suggests an impact of KRASmut in radioresistance that should be further explored in a dose-escalation perspective. Re-biopsy or liquid biopsy may be useful to identify de-novo mutations.
Disparities in stage of diagnosis of colon cancer: Differences by Hispanic background, race, and ethnicity.
Authors: Dimitrios N. Varvoglis, Chris B Agala, Krista M. Perreira, Jose G. Guillem
Journal: Journal of Clinical Oncology (2025)

24 Background: Given noted heterogeneity in Hispanic adults, cancer outcomes reported in aggregate may not detect disparities within specific Hispanic subgroups. The objective was to assess whether any potential differences in colon cancer (CC) stage at diagnosis among patients with Hispanic background (HBackground) could be explained by differences in socio-economic determinants of health (SDOH) including income, education and insurance status. Methods: The National Cancer Database was queried for patients diagnosed with CC from 2004 to 2021. Two logistic regression models generated adjusted odds ratios of late-stage (III-IV) vs early-stage (I-II) CC at diagnosis, disaggregated either by HBackground or R&amp;E, compared to non-Hispanic White (NHW) patients. Model 1 controlled for patient/facility characteristics; Model 2 controlled for additional SDOH. Results: Of the 442,742 CC patients identified, 6% were Hispanics. Compared to NH adults, Hispanic patients were more likely (6% higher odds, p&lt;0.0001) to present with late-stage CC. When Hispanic patients were disaggregated by HBackground, some were more likely (Mexicans 16%; Cubans 20% and South/Central Americans 12%) than NHW adults to present with late-stage CC while others (Puerto Ricans and Dominicans) were not. Disaggregation by R&amp;E indicated that only Hispanic-White patients were more likely (12%) to present with late-stage disease than NHW patients. Controlling for SDOH, R&amp;E differences in stage at diagnosis persisted but HBackground differences became insignificant (Table). Conclusions: Disaggregation of Hispanic adults by HBackground identifies specific subgroups at increased risk for late-stage CC at diagnosis. Understanding modifiable SDOH may identify opportunities for improving early detection of CC and outcomes in specific Hispanic subgroups. Odds of presenting with late-stage colon cancer of “Hispanic” patients disaggregated by race and ethnicity or Hispanic background compared to non-Hispanic Whites. Disaggregation based on: Model 1: Adjusted for age, facility type, year of diagnosis, and Charlson-Deyo comorbidity Model 2: Adjusted for age, facility type, year of diagnosis, Charlson-Deyo comorbidity, neighborhood income, neighborhood education, and insurance status aOR (95% CI) p-value aOR (95% CI) p-value Non-Hispanic White (n=418,046) (ref) (ref) Hispanic White (n=24,058) 1.12 (1.09, 1.15) &lt;.0001 1.04 (1.01, 1.07) 0.01 Hispanic Background Mexican (n=3,612) 1.16 (1.08, 1.24) &lt;.0001 1.05 (0.97, 1.13) 0.25 South/Central American (n= 1,734) 1.12 (1.02, 1.24) 0.02 1.01 (0.91, 1.12) 0.83 Cuban (n=937) 1.20 (1.05, 1.36) 0.001 1.11 (0.97, 1.27) 0.13 Puerto Rican (n=1,280) 1.07 (0.95, 1.19) 0.28 1.01 (0.90, 1.14) 0.88 Dominican (n=465) 1.14 (0.94, 1.39) 0.18 1.02 (0.83, 1.25) 0.85 aOR, Adjusted odds ratio; CI, confidence Interval.
Adjuvant chemoradiation combined with immunotherapy for patients with high-risk resectable extrahepatic cholangiocarcinoma and gallbladder cancer: A phase II, multicenter, randomized controlled trial (ACCORD trial).
Authors: Ming Kuang, Zhenwei Peng, Shun-Li Shen, Shuling Chen, Han Xiao
Journal: Journal of Clinical Oncology (2025)

570 Background: Extrahepatic cholangiocarcinoma (ECC) and gallbladder cancer (GBC), as the majority of biliary tract cancer (BTC), has a markedly high risk of recurrence after surgery. However, adjuvant treatments specifically for resectable ECC and GBC patients are scare and adjuvant chemotherapy alone delivers limited efficacy. Immunotherapy and radiotherapy are potential effective treatments and both of them may synergize with chemotherapy. Methods: ACCORD was a multicenter, phase 2, randomized controlled trial to assess the efficacy and safety of chemoradiation with immunotherapy as an adjuvant treatment in resectable ECC/GBC, compared to observation. The primary endpoint was overall survival (OS) and the secondary endpoints included recurrence-free survival (RFS) and safety. Patients in the chemoradiation-anti-PD-1 group received Camrelizumab intravenously every 3 weeks after surgery. Camrelizumab therapy was not terminated until disease progression, unacceptable toxic effects occurred or informed consent withdrawal. After 2 courses of Camrelizumab treatment, chemoradiation was carried out simultaneously. Patients in the observation group received no anticancer treatment unless relapse was detected. Results: From March 2020 to June 2022, a total of 93 ECC/GBC patients after curative resection were randomized 1:1 into chemoradiation-anti-PD-1 group ( n =46, Camrelizumab + concurrent Capecitabine and radiotherapy) and observation group ( n =47). The 1-year, 2-year and 3-year OS rate were 95.7%, 71.4%, and 58.2% in the chemoradiation-anti-PD-1 group, and 80.9%, 52.9%, 30.5% in the observation group (Hazard ratio (HR) 0.43, 95% confidence interval 0.24-0.79; P =0.004). The 1-year, 2-year and 3-year RFS rate were 78.3%, 54.0%, and 40.3% in the chemoradiation-anti-PD-1 group, and 55.3%, 27.0%, 17.2% in the observation group, with a hazard ratio of 0.46 (95% CI, 0.28 to 0.76; P &lt; 0.001). In the chemoradiation-anti-PD-1 group, the main adverse effect ≥ grade 3 were anemia (7 [15.2%]), dermatitis radiation (5 [10.9%]), and nausea (5 [10.9%]); and 100% of patients completed the whole treatment. Conclusions: Chemoradiation combined with immunotherapy as an adjuvant therapy demonstrated superior survival outcomes over observation in resectable ECC/GBC patients with a well-tolerable safety profile, supporting the potential of this combination treatment as effective adjuvant therapy for these high-risk patients. Clinical trial information: NCT04333927 .