bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends in surgery and overall survival in non-metastatic anal cancer: A population-based analysis.
Authors: Eng Cathy , Conces Madison , Ciombor Kristen Keon , Dorth Jennifer Anne , Meyer Joshua E. , Geiger Timothy , Khan Aimal , Aquino Jeneth , Lockney Natalie A. , Chakravarthy Anuradha Bapsi , Benson III Al Bowen , Shen Chan
Published: January 2025

3

Background:
The incidence of anal cancer has recently exceeded > 10,000 patients/year in the United States. For non-metastatic squamous cell carcinoma of the anal canal (SCCA), concurrent chemoradiotherapy (CRT) followed by abdominoperineal resection (APR) as salvage surgery for non-responders is a key treatment approach. Over the past two decades, findings from phase III trials (RTOG 98-11 and ACT II) have increased our knowledge about appropriate treatment approaches. ACT II indicated that delayed assessment of tumor response and consideration of APR up until 26 weeks is appropriate, as many patients demonstrate delayed response to treatment. Our analysis examines whether current evidence has influenced real-world clinical practice by analyzing trends in rates of primary APR and overall survival (OS) outcomes.
Methods:
We conducted a retrospective cohort study using data from the Surveillance, Epidemiology, and End Results (SEER) registry, including patients diagnosed with non-metastatic SCCA between 2004 and 2020. Patients with T0 or T1N0 stage disease were excluded. Descriptive statistics were generated, and chi-square tests were used to compare characteristics between patients who underwent surgery and those who did not. Temporal trends in surgery and radiation therapy were analyzed using the Cochrane-Armitage trend test. Multivariable logistic regression was employed to identify factors associated with surgery uptake, while OS trends were analyzed using Kaplan-Meier and Cox proportional hazard models.
Results:
A total of 16,718 patients were included, with 33.1% requiring salvage APR following CRT. The proportion of patients requiring surgery significantly declined from 46.6% in 2004 to 31.1% in 2020 (p < 0.001). Factors associated with surgery included younger age, male gender, and non-Hispanic Black race (p < 0.001). Kaplan-Meier analysis revealed significant improvements in OS over the study period (log-rank p = 0.0002), with more recent years (2016-2020) associated with significantly better OS compared to earlier periods (2004-2007, HR = 0.77, p < 0.001).
Conclusions:
The significant decrease in rates of salvage APR for non-metastatic SCCA likely reflects the global impact of recent phase III trials. Meanwhile, OS rates have been steadily improving. These findings suggest improved overall knowledge regarding treatment strategies and highlight the real-world impact of clinical investigation in non-metastatic squamous cell carcinoma of the anal canal.
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: Peng Zhi , Wang Jufeng , Zhang Yanqiao , Li Hongli , Zhao Qun , Zhu Xiaodong , Wei Shaozhong , Cheng Ying , Gu Kangsheng , Bai Jun , Chen Yigui , Zhang Zhongtao , Zhang Jun , Wang Junsheng , Niu Zuoxing , Pan Yueyin , Wang Zhigao , Wang Wenliang , Han Hongxia , Shen Lin
Published: January 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%
Predicting mortality in upper gastrointestinal tract cancer using long short-term memory neural networks.
Authors: Thota Manaswitha , Mahajan Sidharth , Boppana Sri Harsha , Boppana Sri Lasya , Komati Sachin Sravan Kumar , Mintz David
Published: January 2025

340

Background:
Upper gastrointestinal (GI) tract cancers represent a significant global health burden, characterized by high morbidity and mortality rates, with an increasing incidence among aging populations and varying outcomes based on gender and ethnicity. Early prediction of mortality rates in upper gastrointestinal cancer can significantly enhance treatment strategies and patient outcomes. This study describes current trends in upper gastrointestinal cancer and proposes a predictive model, developed using Long Short-Term Memory (LSTM) neural networks to project future trends using demographic data.
Methods:
We extracted mortality data from the Center for Disease Control and Prevention (CDC) Wide-Ranging Online Data for Epidemiological Research (WONDER) Database spanning 1999, normalized it and encoded categorical variables such as age, sex, ethnicity, and race numerically. Using Studio R to analyze mortality trends, we developed an LSTM model known for its ability to capture and utilize long term data patterns. The model, trained with a sequence length of 20, predicted future data points based on the previous 20. We then assessed its accuracy and generalization with a test set. Ultimately, our model is able to utilize demographic variables to forecast annual mortality and survival rates.
Results:
The mortality rates for upper GI tract cancers are notably higher among elderly individuals, particularly those aged 80 and above, with males and certain ethnic groups, such as Hispanics. The accuracy of the trained model was evaluated by calculating the Mean Squared Error (MSE), a measure of the difference between the predicted and actual value, with zero indicating no difference between the two. Our LSTM model achieved a training MSE of 0.00085 and a validation MSE of 0.0016, indicating good reliability and accuracy.
Conclusions:
Our analysis highlighted clear mortality trends and demonstrated the model’s effectiveness in improving mortality predictions in upper gastrointestinal cancer. However, limitations due to the dataset’s lack of clinical variables (such as comorbidities, cancer stage, and prior treatments) and its reliance on a single dataset may affect external validity. Future research is needed to determine if the model can be applied for clinical prognosis or strategic planning. We ultimately created and validated an LSTM neural network model with the CDC WONDER dataset, showing promising results. Future development will aim to include clinical characteristics to create a more personalized predictive tool.
Development and validation of machine learning model for mortality after curative gastrectomy for gastric cancer.
Authors: Park Ki Bum
Published: January 2025

386

Background:
The risk for postoperative complications can significantly impact perioperative planning. The aim of this study is to develop and validate a model based on various machine learning techniques to predict postoperative mortality (PM) after curative radical gastrectomy for gastric cancer.
Methods:
Data from a nationwide survey led by the Korean Gastric Cancer Association was used for the development set, which included 12,722 patients who underwent gastrectomy in 2019 across 68 institutions in South Korea. The validation set comprised 4,887 patients from 8 institutions between 2009 and 2017. PM was defined as all-cause death within 30 days after surgery or in-hospital death beyond 30 days. Five machine learning models (CatBoost, Gradient Boosting, Light GBM, Random Forest, XGBoost) were evaluated using perioperative clinical characteristics. Model performance was assessed using the area under the receiver operation characteristic curve (AUROC) with 5-fold cross-validation.
Results:
The PM rates were 0.83% and 1.04% in the development and validation set, respectively. In the development set, the Random Forest model demonstrated the highest discrimination capacity with an AUROC of 0.772, followed by Gradient Boosting at 0.767, CatBoost at 0.742, XGBoost at 0.732, and LightGBM at 0.717. However, in the validation set, CaBoost showed the highest AUROC at 0.747, while the AUROC for Random Forest decreased to 0.688.
Conclusions:
The CatBoost model demonstrated robust and consistent performance in predicting PM risk across both development and validation datasets. To further enhance the performance of the model and ensure stable clinical application, future research should focus on developing methods for quantitative measurement of perioperative factors such as surgical techniques.
Safety and efficacy of conversion therapy for metastatic esophageal cancer: Exploratory analysis of JCOG1314.
Authors: Matsuda Satoru , Kawakubo Hirofumi , Tsushima Takahiro , Hironaka Shuichi , Tsubosa Yasuhiro , Sakanaka Katsuyuki , Oguma Junya , Kadowaki Shigenori , Tsunoda Shigeru , Hara Hiroki , Koyanagi Kazuo , Yamaguchi Toshifumi , Harada Kazuaki , Takahashi Masanobu , Minashi Keiko , Baba Eishi , Sasaki Keita , Machida Ryunosuke , Takeuchi Hiroya
Published: January 2025

401

Background:
Patients with esophageal cancer (EC) with distant metastasis were treated with systemic chemotherapy. Recent advances in multimodal treatments have made conversion therapy (CT) a viable option for patients with metastatic EC. JCOG1314 was a randomized phase III trial to confirm the survival benefit of docetaxel plus cisplatin plus 5-fluorouracil (DCF) versus cisplatin plus 5-fluorouracil (CF) as initial treatment for unresectable or recurrent esophageal cancer. The purpose of this study was to evaluate the safety and survival impact of CT in patients enrolled in JCOG1314.
Methods:
CT was defined as surgery or chemoradiotherapy (CRT) aiming at cure after initial treatment for tumors that were initially unresectable due to distant metastasis. Clinicopathologic factors, surgical outcomes, toxicities during CRT, and survival were compared between CT and non-CT groups. CTCAE v4.0-JCOG was used to evaluate postoperative complications and adverse events during CRT.
Results:
Between September 2014 and April 2021, 240 patients were randomized to CF or DCF. Excluding patients with recurrent disease, 154 patients with initially unresectable esophageal cancer due to distant metastasis were selected for this study. Among them, 21 patients received CT which included conversion surgery (n=5) and conversion CRT (n=16). There was no significant difference in the number of metastatic organs, depth of invasion of the primary tumor, lymph node metastasis, and chemotherapy regiment between CT and non-CT groups. The most common M1 factor in CT group was the thoracic lymph node, followed by abdominal lymph node and cervical node. In conversion surgery group, there was no incidence of Grade 3 or higher pneumonia/leakage. Regarding the Grade 3 or higher non-hematological toxicities during conversion CRT, the incidence of appetite loss/ oral mucositis/pneumonia was 2 (13%)/2 (13%)/1 (6%), respectively. The 3-year overall survival (OS) of CT and non-CT groups was 52.4% and 14.3%, respectively. On multivariable analysis, patients with CT showed significantly better OS compared with the non-CT group (HR 0.36, 95% CI 0.19-0.67, p<0.01). In patients who underwent CT, there was no significant difference in OS between conversion surgery and CRT groups.
Conclusions:
This study demonstrated that CT was safely performed with favorable prognosis. A prospective study is warranted to investigate whether CT would improve survival in metastatic esophageal cancer.
Neoadjuvant SHR-1701 (a bifunctional anti-PD-L1/TGF-βRII agent) combined with chemoradiotherapy for resectable locally advanced esophageal squamous cell carcinoma (ESCC): A phase II trial.
Authors: Liu Chengixn , Huang Wei , Fu Chengrui , Sun Hongfu , Zhao Qian , Zhao Changhong , Chen Xiaoyu , Li Baosheng
Published: January 2025

410

Background:
Neoadjuvant chemotherapy or chemoradiotherapy followed by surgery is the standard of care for resectable locally advanced ESCC. SHR-1701, a new bifunctional fusion protein composed of a monoclonal antibody against PD-L1 fused with the extracellular domain of TGF-β receptor II, may enhance antitumor activity in combination with neoadjuvant standard therapies in ESCC patients (pts). The aim of this phase II trial is to determine the safety and efficacy of neoadjuvant chemoradiotherapy plus SHR-1701 followed by esophagectomy in pts with locally advanced resectable ESCC.
Methods:
Pts with resectable thoracic ESCC, diagnosed as clinical stage of cT1b-cT2N+M0 or cT3-cT4aNxM0 per AJCC 8th were eligible. Preoperative therapy included SHR-1701 (30 mg/kg every 3 weeks for 2 cycles), albumin paclitaxel (50 mg/m
2
, once a week for 5 weeks), carboplatin (AUC=2, once a week for 5 weeks) and radiotherapy (41.4Gy in 23 fractions). Following esophagectomy, pts received SHR-1701 up to 1 year. The primary endpoint was pathological complete response (pCR) rate in the per-protocol population. Secondary endpoints included R0 resection rate, major pathological response (MPR) rate, disease free survival (DFS) and safety.
Results:
Between Dec. 2021 and Feb. 2023, 43 pts were screened and 41 met the inclusion criteria, among whom the clinical stage I, II, III, and IVa at baseline were 1 (2.4%), 8 (19.5%), 31 (75.6%), and 1 (2.4%), respectively. All 41 pts received neoadjuvant SHR-1701 combined with chemoradiotherapy. As of Mar. 2024, 30 pts underwent surgery, and all achieved R0 resection. There was no in-hospital and postoperative 30-day mortality. 9 (30.0%) pts achieved pCR in both primary tumor and lymph nodes (ypT0N0), and 12 (40.0%) pts had complete pathological response of the primary tumor with residual disease in lymph nodes alone (ypT0N+). Treatment-related adverse events (TRAEs) occurred in all pts, and most of TRAEs were grade 1-2. Notable toxicity included pneumonitis (31.7%) and anastomotic leak (12.2%).
Conclusions:
The addition of SHR-1701 to neoadjuvant chemoradiotherapy in ESCC demonstrated promising efficacy with acceptable toxicity, and might be a promising approach for neoadjuvant treatment. Clinical trial information: ChiCTR2000041562.
Tislelizumab (TIS) + chemotherapy (chemo) vs placebo (PBO) + chemo as first-line (1L) treatment in gastric/gastroesophageal junction adenocarcinoma (GC/GEJC) patients with/without peritoneal or liver metastases: A post hoc analysis of RATIONALE-305 study.
Authors: Qiu Miaozhen , Luo Huiyan , Wang Feng-Hua , Wang Feng , He Ming-Ming , Xu Sheng , Pan Xiaoxi , Xu Rui-Hua
Published: January 2025

414

Background:
Gastric cancer patients with peritoneal or liver metastases had poor prognosis, and the efficacy of immunotherapy in these patients remains unclear. The global phase 3 RATIONALE-305 study (NCT03777657) demonstrated that tislelizumab combined with chemotherapy could bring survival benefits to 1L treatment of GC/GEJC patients. Here, we assessed the efficacy of TIS + chemo vs PBO + chemo in patients with/without peritoneal or liver metastases in RATIONALE-305.
Methods:
Patients with systemic treatment-naïve GC/GEJC were randomly assigned (1:1) to receive either TIS + chemo or PBO + chemo. Regression analyses were conducted to explore the associations between peritoneal or liver metastases and OS. Relative treatment effect between tislelizumab and placebo was assessed in each subgroup. The Kaplan-Meier method was used to estimate the median OS, and hazard ratios (HRs) for OS were estimated using Cox proportional hazards models.
Results:
Among the 997 randomized patients (TIS + chemo, n=501; PBO + chemo, n=496), 434 (43.5%) had peritoneal metastases (220 in TIS arm; 214 in PBO arm) and 378 (37.9%) had liver metastases (190 in TIS arm; 188 in PBO arm) at baseline. Regression analyses showed peritoneal and liver metastases were significantly associated with shorter OS. Baseline characteristics were balanced between TIS and chemo arms within each subgroup, including PD-L1 expression levels. As of data cut-off on Feb 28, 2024, OS was longer in the TIS arm compared with the PBO arm in patients with peritoneal metastases (HR= 0.78, 95% CI 0.64-0.96) or without (HR = 0.79, 95% CI 0.65-0.95). OS improvement was also observed in patients with liver metastases (HR = 0.77, 95% CI 0.62-0.96) or without (HR = 0.80, 95% CI 0.67-0.95).
Conclusions:
This post hoc analysis demonstrated OS improvement with TIS + chemo vs PBO + chemo in GC/GEJC patients with/without peritoneal or liver metastases. To our knowledge, RATIONALE-305 is the first global pivotal study reporting survival benefits with TIS + chemo as 1L treatment for GC/GEJC, irrespective of peritoneal or liver metastases.
Clinical trial information: NCT03777657
.

With metastases
Without metastases

TIS
arm

PBO
arm

TIS
arm

PBO
arm

Peritoneum
n=220
n=214
n=281
n=282

Median OS, mo (95% CI)
12.3 (10.6-14.3)
11.8 (10.6-13.0)
17.3 (15.0-20.3)
14.0 (12.6-16.0)

HR (95% CI)
0.78 (0.64-0.96)
0.79 (0.65-0.95)

Liver
n=190
n=188
n=311
n=308

Median OS, mo (95% CI)
13.9 (11.4-15.6)
12.9 (10.9-14.5)
16.0 (13.6-18.0)
12.9 (11.9-14.4)

HR (95% CI)
0.77 (0.62-0.96)
0.80 (0.67-0.95)
Updated results from the phase Ib/II study of fruquintinib combined with SOX and toripalimab in patients with advanced metastatic gastric/gastroesophageal junction adenocarcinoma (GC/GEJC).
Authors: Meng Xiangrui , Shan Zhengzheng , Guan Lulu , Dao Xin , Fan Qingxia , Wang Feng
Published: January 2025

423

Background:
The efficacy of first-line treatment in advanced GC/GEJC patients (pts) with negative or low PD-L1 expression still needs to be improved. This phase Ib/II, open-label study (NCT05024812) evaluating fruquintinib (a highly selective VEGFR-1, -2, -3 inhibitor) plus toripalimab (anti-PD-1), and SOX has shown preliminary antitumor activity as first-line therapy in GC/GEJC. Here we update the results with longer follow-up duration and a specific focus on PD-L1 CPS features.
Methods:
The study of phase Ib employed a 3+3 dose escalation design, pts were treated with fruquintinib 3mg/d (dose level; DL1), 4mg/d (DL2), or 5mg/d (DL3) po, d1-14, in combination with fixed dose of toripalimab (240mg, iv, d1), oxaliplatin (130 mg/m
2
, iv, d1) and S-1 (40-60mg based on BSA, po, d1-14) every 3 weeks. It had been reported in phase Ib that fruquintinib 5mg/d was defined as the RP2D. In phase II, a further 64 pts would be treated with the same regimen. Primary endpoint of phase II was PFS per RECIST 1.1. Secondary endpoints included ORR, DCR, OS, DOR and safety.
Results:
As of August 15, 2024, 32 pts (9 in phase Ib; 23 in phase II) had been enrolled. Pts characteristics included: median age 62 (range 38–73); 66% male; 88% with ECOG PS 1, and 31% with liver metastasis. 31 pts had PD-L1 CPS available. 40.6% were CPS < 1 and 68.8% were CPS < 5. Of the 30 pts evaluable for tumor response, the ORR was 63.5% (95% CI 43.9–80.1) with 4 pts achieving complete responses and DCR was 96.7% (95% CI 82.8–99.9). After a median follow-up of 10.94 months, the median PFS was 9.33 (95% CI: 5.68–NA) months and OS result was not reached. Pts with CPS < 5 were more likely to achieve higher response rate (65.0 vs 55.6%) and longer PFS than CPS ≥5 (12.68 vs 8.11 months). Similar trends were observed in pts with CPS < 1 and CPS ≥1 (ORR: 75.0 vs 52.9%; PFS: 12.68 vs 8.11 months). Treatment-related adverse events (TRAEs) were mainly grade 1-2 and the most common ones were hypoalbuminemia (50%), neutrophil count decreased (34%), anemia (41%), platelet count decreased (34%) and white blood cell decreased (34%). Grade 4 TRAEs occurred in 2 pts (impaired liver function, hypertriglyceridemia). There were no treatment related deaths in the trial.
Conclusions:
Fruquintinib combined with SOX and toripalimab provided favorable efficacy and manageable toxicity profile as first-line therapy for pts with advanced metastatic GC/GEJC, especially in pts with negative or low PD-L1 expression. More data including the potential predictive response biomarkers would be further analyzed and reported.
Clinical trial information: NCT05024812
.
Perioperative chemoimmunotherapy for patients with gastric or gastroesophageal junction cancer: A systematic review and meta-analysis.
Authors: Omori Reo , Fujiwara Yu , Tokunaga Kota , Sato Takumi , Mukherjee Sarbajit
Published: January 2025

430

Background:
Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis, in combination with chemotherapy, are known to improve survival in advanced/metastatic gastric (GC) or gastroesophageal junction cancer (GEJC). Therefore, several trials incorporated ICIs in the neoadjuvant/peri-operative setting with promising preliminary results. The purpose of this meta-analysis was to determine the safety and efficacy of neoadjuvant chemoimmunotherapy for resectable GC or GEJC.
Methods:
PubMed/MEDLINE and Embase were systematically searched for randomized control trials (RCTs) investigating the efficacy of neoadjuvant anti PD-1/PD-L1 ICIs for locally advanced GC or GEJC up to 07/27/2024. Outcomes of interest were surgical outcomes such as pathological complete response (pCR) rate and major pathological response (MPR) rate. Risk ratio (RR) with 95% confidence intervals (CI) were pooled using a fixed model meta-analysis. Statistical analysis was performed with Review Manager 5.4.1.
I²
statistics was used to assess heterogeneity. The Cochrane risk of bias assessment tool was used to assess the risk of bias. All analyses were conducted at a significance level of 0.05.
Results:
Seven RCTs comprising 2,911 GC or GEJC patients were included. Among these, 1,454 patients received neoadjuvant chemoimmunotherapy and 1,457 patients received chemotherapy, respectively. Neoadjuvant chemoimmunotherapy significantly improved pCR rate (RR 2.94; 95% CI 2.34-3.70; P<0.00001;

I
2

=33%), and MPR rate (RR 1.47; 95% CI 1.25-1.72; P<0.00001;

I
2

=30%) compared to chemotherapy alone. Chemoimmunotherapy was associated with slightly higher incidence of grade 3 or worse treatment-related adverse events than chemotherapy (RR 1.07; 95% CI 1.01-1.14; p=0.03;

I
2

=0%).
Conclusions:
This meta-analysis showed that adding ICIs to chemotherapy significantly improved the pCR and MPR rates and was feasible for patients with locally advanced GC or GEJC. Results of survival outcomes in the included trials and ongoing trials are awaited to further determine the efficacy and utility of chemoimmunotherapy and identify patient populations that benefit from this strategy.

Included studies.

Author
Year
Trial#
Design
Cancer; Stage
Name of IO
Target
Chemo regimen
Extracted data

pCR

MPR

TRAE

Ding X
2023
NCT04982939
P2
G/GEJ; Stage2-3
Sintilimab
PD-1
SOX
○
○
　

Janjigian YY
2023
NCT04592913
P3
G/GEJ; ≥T2Nany/T0-4 N+
Durvalumab
PD-L1
FLOT
○
　
○

Li C
2023
NCT04208347
P3
G/GEJ; T3-4aN+
Camrelizumab
PD-1
SOX(+apatinib)
○
○
　

Lin JX
2024
NCT04195828
P2
G; T2-4N+
Camrelizumab
PD-1
S-1+nabPTX
○
○
○

Lorenzen S
2024
NCT03421288
P2
G/GEJ; ≥T2 and/or N1
Atezolizumab
PD-L1
FLOT
○
○
　

Peng Z
2024
NCT04661150
P2
G/GEJ HER2+; resectable
Atezolizumab
PD-L1
CAPOX+Tmab
○
　
　

Shitara K
2024
NCT03221426
P3
G/GEJ; ≥T3N+
Pembrolizumab
PD-1
FLOT or XP/FP
○
　
○

Yuan SQ
2024
NCT04250948
P2
G/GEJ; T3-4N+
Toripalimab
PD-1
SOX/CAPOX
○
○
○
Effect of tRF-28-ZJ47D112Z4DZ on the pathogenesis of gastric cancer through targeting cyclin D1/CDK4 and its early diagnostic value.
Authors: Yu Xiuchong
Published: January 2025

475

Background:
Gastric cancer exhibits high incidence and mortality rates worldwide. Current research on gastric cancer aims to discover stable and effective early diagnostic markers, as well as uncover the disease's pathogenesis. tRNA-derived fragment (tRF) is a newly discovered regulatory non-coding RNA, which plays an important role in tumor diagnosis and treatment.
Methods:
This study, through transcriptome sequencing and MINTBase v2.0 database, screened out a new molecule tRF-28-ZJ47D112Z4DZ (tRF-28) related to gastric cancer. An absolute quantitative method was established to quantify the level of tRF-28 in plasma. ROC curve, survival curve, Cox regression model were constructed, and clinicopathological factors were collected to analyze the diagnostic value of tRF-28. "Overexpression" and "knockdown" tRF-28 gastric cancer cell models and xenograft tumor models were established to study the effects of tRF-28 on cell proliferation. Using bioinformatics, qRT-PCR, Western blot, dual luciferase reporter gene, fluorescence in situ hybridization, RNA binding protein immunoprecipitation assay, rescue experiment and immunohistochemistry to study the regulatory role of tRF-28 by binding to the 3'UTR of CCND1.
Results:
This study clarified the tRF-28 levels in the plasma of healthy individuals, and gastric benign and malignant lesions, providing a new candidate biomarker for the early diagnosis of gastric cancer. Through upregulating and downregulating the level of tRF-28 in gastric cancer cells, it was revealed that tRF-28 inhibits the proliferation of gastric cancer cells in vivo and in vitro by regulating key proteins such as Cyclin D1, CDK4, Rb, and p-Rb. In studying specific molecular mechanisms, tRF-28 and CCND1 were co-located in the cytoplasm. tRF-28 combines with Ago2 protein to form a complex and plays a role in silencing the target gene CCND1 in the cytoplasm. The rescue experiments revealed that silencing the target gene CCND1 can reverse the carcinogenesis effect of tRF-28 inhibitors, clarifying the biological functions of tRF-28 by regulating CCND1.
Conclusions:
Based on a series of research findings, we elucidated that tRF-28 form a complex with Ago2 protein, binding to the 3' UTR of CCND1 to downregulate Cyclin D1, CDK4, and other critical proteins, thereby inhibiting the proliferation of gastric cancer cells. Our study aims to offer new insights into identifying potential early diagnostic markers and therapeutic targets for gastric cancer.
Use of nucleotyping and tumor stroma ratio to predict prognosis in patients with resected intestinal-type gastric cancer.
Authors: Sha Dan , Sun Jing , Sinicrope Frank A. , Tian Chunfang , Jing Haiyan , Wang Jinshen , Zhuang Qingchun , Yang Qian , Song Wei
Published: January 2025

483

Background:
Heterogeneity exists in recurrence and survival among patients with intestinal-type gastric cancer (IGC). Nucleotyping is the alterations in chromatin organization. We sought to identify the prognostic utility of nucleotyping, tumor stroma ratio (TSR) and DNA ploidy in these patients.
Methods:
Radical resection of gastric carcinoma (> 15 LNs removed) was performed in 283 patients (stage I, n=73; stage II, n=102; stage III, n=108) at our university hospital between 2010 and 2018. Automated image cytometry tools were used to quantitatively measure nucleotyping, TSR and DNA ploidy. Cutpoints of nucleotyping and TSR were 0.044 and 50%, respectively. Associations of these features with clinicopathological characteristics, time-to-recurrence (TTR) and cancer specific survival (CSS) were analyzed by univariate and multivariate analysis.
Results:
Among 283 patients, chromatin heterogeneity, high TSR and non-diploid were significantly associated with larger tumor size, higher T and N stage, and poorer TTR and CSS at 5 years. In a Cox multivariable analysis, nucleotyping and TSR were independently associated with TTR and CSS (P＜0.05) (Table). The top three contributors to TTR were N stage (33.9%), nucleotying (29.7%) and TSR (25.5%). The top three contributors to CSS were N stage (35.6%), nucleotying (29.7%) and TSR (18.0%). As a combined variable, the percent relative contribution of nucleotyping and TSR ranked first for TTR and CSS (56.0%, 50.0%), ahead of N stage (33.4%, 34.6%) and TILs (8.4%, 10.6%).
Conclusions:
Nucleotyping and TSR were each significantly and independently associated with TTR and CSS, and their combined variable was more strongly prognostic than either alone.

Cox multivariable analysis of TTR and CSS.

Features
TTR HR (95%CI)
TTR P value
CSS HR (95%CI)
CSS P value

Tumor size (>3cm vs ≤3cm)
1.10 (0.48-2.54)
0.83
0.77 (0.35-1.70)
0.56

T stage (T3-T4 vs T1-T2)
1.07 (0.46-2.49)
0.87
1.41 (0.53-3.76)
0.49

N stage (N2N3 vs N0N1)
2.84 (1.39-5.78)
<0.01
7.69 (3.37-17.55)
<0.01

Adjuvant Therapy (with vs without)
1.32 (0.72-2.40)
0.37
0.85 (0.48-1.52)
0.59

TB (high vs low)
1.29 (0.62-2.69)
0.50
1.61 (0.85-3.07)
0.15

TILs（low vs high）
1.73 (0.96-3.13)
0.07
1.90 (1.06-3.40)
0.03

Nucleotyping (Chromatin heterogeneous vs Chromatin homogeneous)
2.19 (1.21-3.99)
0.01
3.44 (1.96-6.03)
<0.01

TSR (high vs low)
2.12 (1.16-3.82)
0.01
2.51 (1.43-4.41)
<0.01

DNA ploidy (Non-diploid vs Diploid)
1.20 (0.55-2.63)
0.65
0.98 (0.44-2.15)
0.95

1 TTR, time-to-recurrence; 2 CSS, cancer specific survival.
The Gastric Cancer Registry: A multi-omic cellular and molecular resource for cancer biomarker and therapeutic discovery.
Authors: Ji Hanlee P. , Meka Rithi , Wichmann Perez Ignacio , Grimes Susan M. , Lee Hojoon , Wang Yan , Sathe Anuja
Published: January 2025

491

Background:
The Gastric Cancer Registry (GCR) is a comprehensive clinical and genomic data resource focused on gastric cancer (GC) patients and individuals with a family history of GC or a germline CDH1 mutation. As part of the GCR’s ongoing enrollment, patients contribute cancer history information, archival tumor samples and other biospecimens. The cancer samples undergo extensive molecular and cellular analysis that includes genomic sequencing and spatial analysis. We have generated a robust dataset, publicly accessible online through the GCR Genome Explorer (GCR-GE). This genomic, molecular and cellular resource provides a rich data set that accelerates multidisciplinary research aimed at improving detection and treatment strategies for GC. GC disproportionately affects Latin American populations - we have included new cohorts from Latin America. The GCR enables researchers, clinicians and patients to address specific questions about the molecular and cellular basis of GC.
Methods:
GC samples underwent whole genome, whole exome, and bulk RNA sequencing were conducted. The genomic features identified include copy number variation, gene mutations, gene expression, microbiome composition, estimation of tumor-infiltrating immune cells, tumor neoantigens, MSI/MSS status, and HLA subtypes. In addition to genomic data, clinical data was compiled from survey responses and pathology reports and integrated into the GCR-GE. We have incorporated single cell and spatial analysis that includes diverse cell types, single cell gene expression and cellular architecture in native tumor tissues. This data was released to the GCR Genome Explorer website.
Results:
A total of 817 subjects have enrolled in the GCR including 598 diagnosed with GC and 219 at high-risk for GC through family history of GC and/or a CDH1 mutation. Of the 598 with GC, some met multiple criteria including at least 40 with a family history of GC, 10 with a CDH1 mutation, and 18 with both a family history of GC and a CDH1 mutation. The GCR-GE includes data from 257 gastric tumors in addition to external datasets from TCGA. In the latest data release, clinical and genomic data from 78 gastric tumors from patients in Latin America were integrated into the GCR-GE.
Conclusions:
The GCR is a comprehensive database of crucial clinical and genomic data necessary for driving forward GC research. Through global expansion, the GCR has generated a more representative dataset by increasing racial diversity and including underrepresented populations that are at higher risk for GC.
Ethnic and socioeconomic disparities in cancer-free and all-cause survival in cholangiocarcinoma patients under 60: A population-based study.
Authors: Dharia Adit , Mahayni Abdulah Amer , Borra Rahul , Peshin Supriya , Ser-Manukyan Haik , Mangu Sainarayana , Patel Dharmik M , Muddassir Salman
Published: January 2025

527

Background:
Cholangiocarcinoma in individuals under 60 years of age is rare, and survival outcomes can vary based on ethnic and socioeconomic factors. While previous studies have examined these disparities in other cancers, little is known about their impact on cancer-free and all-cause survival in younger cholangiocarcinoma patients. This study investigates the role of race and income in survival outcomes for this population.
Methods:
Data for individuals under 60 diagnosed with cholangiocarcinoma were extracted from the Surveillance, Epidemiology, and End Results (SEER) 22 registry. Kaplan-Meier curves were constructed to assess overall and cancer-free survival. Median survival times were calculated for each racial and income group, and log-rank tests were used to compare survival differences across the groups.
Results:
A total of 11,214 individuals under 60 years of age diagnosed with cholangiocarcinoma were included. Median all-cause survival was 12.0 months for Asian patients, 11.0 months for White patients, and 9.0 months for both Black and Hispanic patients. Significant differences were observed between Asian vs White (p < 0.005), Asian vs Black (p < 0.005), Asian vs Hispanic (p < 0.005), White vs Black (p < 0.005), and White vs Hispanic (p < 0.005), with no significant difference between Black and Hispanic patients (p = 0.859). For cancer-free survival, the median was 13.0 months for Asians, 12.0 months for Whites, 11.0 months for Blacks, and 10.0 months for Hispanics, with significant differences between Asian vs Black (p < 0.005), Asian vs Hispanic (p < 0.005), and White vs Black (p = 0.017). The difference between Asian vs White was not statistically significant (p = 0.052), and no significant difference was observed between White vs Hispanic (p = 0.418) or Black vs Hispanic (p = 0.418). By income, patients with an income >$75,000 had significantly longer all-cause survival (12.0 months vs 9.0 months, p < 0.005) and cancer-free survival (13.0 months vs 11.0 months, p < 0.005) compared to those with an income of $0-$75,000.
Conclusions:
Significant disparities in cancer-free and all-cause survival were found based on ethnicity and income. Asian and White patients had longer survival compared to Black and Hispanic patients, and higher-income patients experienced better outcomes. These findings highlight the need for targeted efforts to address healthcare inequalities in cholangiocarcinoma care.
Non-contrast MRI as a surveillance tool for recurrent hepatocellular carcinoma after curative treatment: A prospective multicenter intra-individual comparison trial.
Authors: Lee Dong Ho
Published: January 2025

530

Background:
Hepatocellular carcinoma (HCC) often recurs following curative treatment, significantly impacting long-term survival. Contrast-enhanced multiphasic computed tomography (CECT) is widely utilized for HCC recurrence surveillance but carries risks such as radiation exposure and adverse reactions to contrast agents. This prospective multicenter trial aimed to compare the accuracy of non-contrast abbreviated magnetic resonance imaging (NC-MRI) with CECT in detecting late recurrent HCC.
Methods:
This prospective multicenter intra-individual head-to-head comparison trial (study identifier: NCT05690451, KCT0006395) enrolled participants who had undergone curative treatment for HCC and remained recurrence-free for over two years. Participants underwent three rounds of surveillance at 2–6-month intervals using both CECT and NC-MRI. The primary outcome was the detection accuracy of each modality, compared using the McNemar test. Secondary outcomes included detection sensitivity and specificity.
Results:
A total of 203 participants underwent 528 rounds of paired CECT and NC-MRI, detecting recurrent HCC in 22 participants (10.8%). Among these cases, 21 showed intrahepatic recurrent HCC with a median tumor size of 1.3 cm, and one exhibited aortocaval lymph node metastasis. NC-MRI demonstrated a detection accuracy of 96.6% (196/203), significantly higher than CECT's 91.6% (186/203) (P=0.006). NC-MRI also exhibited significantly higher sensitivity in detecting recurrent HCC compared to CECT (77.3% [17/22] vs. 36.4% [8/22]; P=0.012), while specificity did not differ significantly between NC-MRI and CECT (98.9% [179/181] vs. 98.3% [178/181]; P=0.999).
Conclusions:
NC-MRI showed significantly higher sensitivity and accuracy in detecting recurrent HCC among patients who had been disease-free for more than two years after curative treatment, establishing it as the preferred surveillance modality for late recurrence.
Clinical trial information: NCT05690451
.

Contrast enhanced CT
Non-contrast MRI
Difference, % (95% CI)
P-value

Estimates, % (n/N)
95% CI, %
Estimates, % (n/N)
95% CI, %

Accuracy
91.6% (186/203)
87.8-95.5
96.6% (196/203)
94.0-99.1
4.9 (1.7, 8.2)
0.006

Sensitivity
36.4% (8/22)
14.5-58.2
77.3% (17/22)
58.3-96.3
40.9 (16.8, 65.0)
0.012

Specificity
98.3% (178/181)
96.5-100
98.9% (179/181)
97.4-100
0.6 (-0.5, 1.6)
0.999
Characterization of the real-world first line (1L) use of single dose tremelimumab regular interval durvalumab (STRIDE), for treatment of unresectable hepatocellular carcinoma (uHCC), using two electronic medical record (EMR) databases.
Authors: Chauhan Aparna , Farid-Kapadia Mufiza , Goel Hersh , Valerio Stephen J. , Vaidya Neel
Published: January 2025

534

Background:
In October 2022, the US FDA approved the STRIDE (Single Dose Tremelimumab Regular Interval Durvalumab) regimen, comprising tremelimumab 300 mg for 1 dose plus durvalumab 1500 mg every 4 weeks, for the 1L treatment of uHCC in adults aged ≥18 years. Thus far there is limited data characterizing STRIDE's 1L use in the real world. This observational study aims to describe patient characteristics, and clinical profiles of a 1L STRIDE cohort.
Methods:
A retrospective cohort study was conducted using EMR data from two community oncology practice networks, Florida Cancer Specialists and American Oncology Network, from January 1, 2018, to March 31, 2024. Adults with HCC who received ≥1 administration of the STRIDE regimen as 1L treatment following diagnosis were included. Patients with evidence of other cancers or systemic therapies pre-index date were excluded, to establish a cancer-naïve cohort at index. Index date was first administration of STRIDE. The analysis described the patient characteristics and clinical profile at index date. Patient demographics, severity indicators (cancer stage, albumin-bilirubin index (ALBI), alpha fetoprotein (AFP), Eastern Cooperative Oncology Group (ECOG)) and lab data were assessed on or closest to index date.
Results:
79 patients initiated the 1L STRIDE regimen. The median (P25, P75) age at index was 70 (63.2-76.4) years. 72.2% were males, 64.6% were white, and 69.6% were overweight or obese patients. 95% had their first HCC diagnosis between 2022-2024 and the mean time from diagnosis to index date was 3.8 months (SD: 10.2). Among patients with reported cancer stage (n=57), most (82.5%, n=47) were diagnosed with stages IIIA to IVB. 18% had ECOG scores ≥2. 86% had ALBI grades between 2-3; 42.1% had AFP level ≥400 ng/ml; 30.4% had cirrhosis (among those that reported comorbidities) and 24.1% received any loco-regional therapy.
Conclusions:
Our study provides a real-world profile of patients on 1L STRIDE. Compared to the HIMALAYA trial, these findings suggest that patients in this real-world study tend to be older, diagnosed at late-stage, have a poor liver profile, and potentially worse prognosis over time. Further research is required to explore treatment pathways after index date, over a long follow-up, which may provide more insight into the continuity and effectiveness of IL STRIDE in the real-world.
Real-world survival differences in advanced biliary tract cancer patients with ctDNA detected IDH1 mutations and FGFR2 fusions receiving first-line gemcitabine-cisplatin with and without immunotherapy.
Authors: Kim Richard D. , Lewis Courtney , Bubie Adrian , Zhang Nicole , Clemens Keelia
Published: January 2025

548

Background:
Comprehensive genomic profiling (CGP) is recommended for patients (pts) with metastatic BTC (mBTC) given its aggressive, heterogeneous disease profile. Liquid biopsy is a rapid, non-invasive option with high concordance to tissue-based CGP. First-line (1L) therapy in mBTC is gemcitabine-cisplatin (GemCis) +/- durvalumab or pembrolizumab (IO) regardless of CGP results. However, data suggests pts with targetable alterations may have worse outcomes with addition of IO compared to all comers. We examined outcomes for mBTC pts receiving 1L GemCis vs. GemCis+IO following ctDNA-detected
IDH1
mutation (
IDH1
+) or
FGFR2
fusion (
FGFR2
+).
Methods:
Real-world data was sourced from GuardantINFORM, which comprises aggregated commercial payer health claims and de-identified records from pts with clinical ctDNA testing via Guardant360 (G360). Pts with mBTC and >1 treatment claim after G360 results, and IDH+ or FGFR2+ between April 2019 and June 2024 were analyzed. Only pts treated with 1L GemCis +/- IO were included. Outcomes were assessed via real-world time to treatment discontinuation (rwTTD), real-world time to next treatment (rwTTNT), and real-world overall survival (rwOS), all in months with 95% confidence intervals. Log-rank test was used to compare Kaplan-Meier survival curves.
Results:
412 pts were
IDH1+
and 154 were
FGFR2+
. In the
IDH1
+ cohort, 184 pts were treated with GemCis and 106 pts with GemCis+IO. Pts receiving GemCis demonstrated improved rwOS vs. GemCis+IO [27.2 (23.6-37.8) vs. 16 (13.6-19.9) mo.; HR=0.4 (95CI 0.27-0.59), p<0.001]; there was no difference in rwTTNT [13 (10.8-14.3) vs. 10 (8.4-12.3); HR=0.85(95CI 0.6-1.22), p=0.4] or rwTTD [4.8 (4.1-5.5) vs. 6.6 (4.7-8.1); HR=1.17 (95CI 0.9-1.5), p=0.25]. Similarly, in the
FGFR2
+ cohort, pts receiving GemCis + IO (n=44) had worse rwOS than pts on GemCis (n=70) [NR (15.6-NR) vs. 43 (34.2-2.1); HR=0.37(95CI 0.18-0.74), p=0.005], with no difference in rwTTNT [8.9 (4.89-NR) vs. 13.78 (7.42-NR); HR=0.63 (95CI 0.36-1.1), p=0.1] or rwTTD [5.0 (3.1-7.8) vs. 4.2 (3.5-5.5); HR=1.08 (95CI 0.72-1.6), p=0.7]. Among all mBTC pts receiving GemCis+IO (n=1113), non-
IDH1
+ pts (n=1007) had numerically better rwOS compared to
IDH1
+ pts (n=106) [18.6 (17.2-21.3) vs. 16.0 (13.6-19.);HR=0.76 (95CI 0.6-1.03), p=0.075]. No survival difference was observed between
IDH1+
(n=184) and non-
IDH1
+ (n=2333) pts receiving GemCis [27.2 (23.6-37.8) vs. 26.2 (24.5-28.2); HR=1.08 (95CI 0.88-1.32), p=0.4].
Conclusions:
Addition of IO to GemCis in
IDH1
+ and
FGFR2
+ mBTC pts resulted in decreased rwOS. This data supports ctDNA CGP to inform clinical decision-making prior to 1L as well as at progression. Further studies in clinical cohorts are needed to confirm these findings.
Neoadjuvant immune checkpoint blockade in resectable hepatocellular carcinoma: A systematic review and meta-analyisis.
Authors: Leite da Silva Luís Felipe , Almeida Luiz F. Costa , Cappellaro Anelise Poluboiarinov , Noronha Mariana Macambira , Belotto Marcos , Peixoto Renata D'Alpino
Published: January 2025

590

Background:
Hepatocellular carcinoma (HCC) presents a significant therapeutic challenge due to its high recurrence rates after curative-intent resection. Neoadjuvant immune checkpoint blockade (ICB) has emerged as a promising strategy to improve tumor control by modulating the immune microenvironment prior to surgery. This systematic review and meta-analysis aim to assess the safety and efficacy of neoadjuvant ICB in improving clinical outcomes for patients with resectable HCC.
Methods:
A systematic search of PubMed, EMBASE, and Cochrane databases was conducted to identify clinical trials examining neoadjuvant ICB in resectable HCC. Primary endpoints included pathological complete response (pCR), major pathological response (mPR), overall response rate (ORR), and grade 3-4 treatment-related adverse events (TRAE). Prespecified subgroup analyses were conducted for studies combining ICB with tyrosine kinase inhibitors (TKIs) or dual ICB therapies. Pooled proportions were calculated using a random-effects model via the R package "meta." Inter-study heterogeneity was assessed using the I² statistic and test for subgroup differences were conducted.
Results:
Out of 1,321 studies screened, 14 clinical trials involving 252 patients with resectable HCC were included. Most studies were phase II trials (57%), and patient median age ranged from 57.5 to 68.0 years, with 88.3% of patients being male. The pooled prevalence of mPR was 32% (95% CI, 24–42%; I² = 9%)while pCR was achieved in 24% (95% CI, 17–34%; I² = 29%)of patients. The ORR was 27% (95% CI, 18–39%; I² = 49%), and severe adverse events (grade 3-4 TRAE) had a pooled prevalence of 24% (95% CI, 17–34%; I² = 16%). Subgroup analysis of trials combining ICB with TKIs showed an ORR 34% (95% CI, 20–55%; I² = 60%), an mPR rate of 27% (95% CI, 19–40%; I² = 0%), and a pCR rate of 20% (95% CI, 14–30%; I² = 0%). Dual ICB therapies demonstrated a higher mPR rate of 42% (95% CI, 26–67%; I² = 16%) and a pCR rate of 41% (95% CI, 29–59%; I² = 29%), but were associated with a higher incidence of severe TRAE (41%; 95% CI, 29–60%; I² = 0%).
Conclusions:
Neoadjuvant ICB demonstrates promising efficacy in resectable HCC, particularly when combined with TKIs or dual ICB therapies. While dual ICB enhances pathological response rates, it is associated with higher rates of severe TRAE. These results highlight the need of further studies to optimize combination strategies that balance efficacy and safety for patients with resectable HCC.