bluuebunny/crossref_metadata_2025 huggingface dataset:
Prognostic implication of body composition changes in patients with borderline resectable/locally advanced pancreatic adenocarcinoma (PDAC) treated with mFOLFIRINOX.
Authors: Lee Jong Hyuk , Jeong Hyehyun , Ko Yousun , Kim Kyung Won , Yoon Hyunseok , Kim Kyu-Pyo , Yoo Changhoon , Kim Tae Won , Kim Sun Young
Published: January 2025

783

Background:
Although cachexia is a known prognostic factor in patients with advanced cancer, individual body composition changes during chemotherapy and their association with survival in PDAC warrant further investigation. We aimed to analyze the prognostic implication of comprehensive body composition, including areas and attenuation of muscle mass, body fat area and its distribution, and body mass index (BMI) during mFOLFIRINOX in patients with PDAC.
Methods:
Patients with borderline resectable or locally advanced PDAC, who were not able to undergo curative surgery and received first-line mFOLFIRINOX between January 2017 and December 2020 from Asan Medical Center, Seoul, Korea, were included in this retrospective study if they had paired CT scans of the abdomen at baseline and after 12 weeks of mFOLFIRINOX. Body composition was measured using artificial intelligence software (AID-UTM, iAID Inc.) from the CT images, and their association with overall survival (OS) were analyzed.
Results:
A total of 377 patients were included. Median age was 63 (range, 56–69) and 214 patients (56.8%) were males and 163 patients (43.2%) were females. During the first 12 weeks, significant changes in the body composition occurred as follows (median changes and interquartile range): skeletal muscle area, -5.8% [-11.1%–0.6%]; normal attenuation muscle area/total attenuation muscle area, -2.8% [-8.7%–3.2%]; visceral fat area (VFA), -6.1% [-23.7%–18.6%]; skeletal fat area (SFA), -12.2% [-27.8%–77.1%]; and BMI, -2.2% [-6.8%–1.5%]. Furthermore, changes in the VFA and BMI was associated with tumor response (Kruskal-Wallis test,
p
= 0.012 for VFA;
p
= 0.054 for BMI). There was no significant relationship between body composition abnormalities including sarcopenia, myosteatosis, or obesity at baseline and OS. However, patients who experienced the greatest decrease in SFA and BMI after 12 weeks of mFOLFIRINOX had poorer OS (tertile 1 [greatest decrease] vs 3 [smallest decrease]: HR 0.67 [95% CI, 0.52–0.87] for SFA,
p
= 0.003; 0.68 [95% CI, 0.49–0.83] for BMI,
p
= 0.001).
Conclusions:
In patients with borderline resectable/locally advanced PDAC, body composition significantly changes during the first 12 weeks. Decrease in the body fat and BMI from baseline were associated with poorer tumor response and OS.
Distribution of lymph node metastasis and prognosis in duodenal bulb tumors: A multicenter retrospective study.
Authors: Hisaoka Kazuhiko , Matsuda Satoru , Kawakubo Hirofumi , Takeuchi Masashi , Wada Takeyuki , Sekine Shigeki , Takamoto Takeshi , Tsutsui Mai , Yura Masahiro , Ishida Hiroki , Ono Yoshihiro , Kamiya Satoshi , Bando Etsuro , Nunobe Souya , Kinoshita Takahiro , Kitagawa Yuko
Published: January 2025

797

Background:
Duodenal tumors, especially duodenal bulb tumors, is a relatively rare malignancy of the gastrointestinal tract. The optimal surgical procedure for primary duodenal tumors has not been established because of its low incidence. The purpose of this study was to examine the distribution of lymph node (LN) metastasis in duodenal bulb tumors. Specifically, in T1a and T1b tumors, we aimed to evaluate the feasibility of distal gastrectomy with duodenal bulb resection combined with lymphadenectomy of regional gastric LNs.
Methods:
Data from patients who underwent surgery for either adenocarcinoma or neuroendocrine tumor located in the duodenal bulb between 2000 and 2020 were retrospectively analyzed from five high-volume centers in Japan. Patient background, clinicopathological factors, type of surgery, distribution of LN metastasis, and long-term outcomes were evaluated.
Results:
Of the 128 patients evaluated, LN metastasis was observed in 36%. The frequency of LN metastasis in T1b was 18%. Metastatic LNs were identified in #3, #5, #6, #8a, #8p, #12a, and #13 in T1b. The distribution of LN metastasis in T1b was similar between adenocarcinoma and neuroendocrine tumors. The 3 years overall survival rate in T1a, T1b, and T2–4 was 100%, 93%, and 64%, respectively. ln T1b, while there were three patients with a recurrence, two cases were observed in distant organs without regional LNs, and one patient who underwent pancreaticoduodenectomy had metastasis in the gastric regional LNs.
Conclusions:
Based on the distribution of LN metastasis with pT1, distal gastrectomy with duodenal bulb resection and regional LN dissection is considered a curative treatment. Conversely, pancreaticoduodenectomy is recommended in tumors with T2 or deeper.
Retrospective study evaluating the genomic landscape of anal squamous cell carcinoma using liquid biopsy.
Authors: Conces Madison , Solomon Sheila R. , Selfridge J. Eva , Lumish Melissa Amy , Bajor David L. , Chakrabarti Sakti , Mohamed AMR , Mahipal Amit
Published: January 2025

8

Background:
Advanced-stage squamous cell carcinoma of the anus (aSCCA) is a rare malignancy. Diagnostic biopsies are often inadequate for tissue-based genomic profiling, thus genomic profiles are largely unexplored in this setting. We assessed liquid biopsy NGS results of aSCCA patients (pts) and described genomic profiles by age and sex. To our knowledge, we are the first to describe genetic alterations by liquid biopsy in this patient population.
Methods:
Pts with aSCCA who underwent circulating tumor DNA (ctDNA) NGS with Guardant360 assays from 2017 to 2024 were included. Frequency of alterations were assessed based on sex and age (18-49 years (yrs), ≥50 yrs). Co-occurrence patterns were assessed using cBioPortal. Demographics were extracted from test requisition forms. Statistical analyses via two sided t-tests were performed with significance defined as p<0.05.
Results:
646 pts with aSCCA had non-synonymous ctDNA alterations detected; 69.2% (N=447) were female and 30.8% (N=199) male. Median age was 66 yrs (32-94) with 9.9% (N=64) <50 yrs and 90.1% (N=582) ≥50 yrs. Most frequently altered genes were
PIK3CA
(17.3%),
TP53
(9.8%),
ATM
(7.8%),
EGFR
(4.3%), and
BRCA2
(4.2%). More unique genes were altered in ≥50 yrs cohort [53 mutations, 38 genes with copy number amplification (CNA)] vs <50 yrs cohort (30 mutations, 66 CNA). Most frequent genes altered in <50 yrs cohort were
TP53
(17.6%),
PIK3CA
(13.2%),
EGFR
(11.0%),
APC
(4.4%), and
MET
(4.4%).
PIK3CA
(16.7%),
TP53
(12.2%),
ATM
(8.8%),
BRCA2
(5.5%), and
EGFR
(3.4%) were most frequent in ≥50 yrs cohort. More genes were altered in females (64 mutations, 32 CNA) vs. males (56 mutations, 41 CNA). Most frequent alterations in females were
PIK3CA
E545K (3.4%),
PIK3CA
CNA

(2.8%),
PIK3CA
E542K (1.9%), and
ATM
CNA (1.0%) vs in male pts being
PIK3CA
E545K (4.8%),
PIK3CA
CNA (3.3%),
PIK3CA
E542K (3.3%),
EGFR
CNA (1.6%),
TERT
promoter (1.0%). Overall,
PIK3CA
and
TP53
alterations were mutually exclusive (odds ratio 0.43, p<0.001).
Conclusions:
Liquid biopsy is feasible in patients with aSCCA. Most frequently detected alterations and CNAs were in
PIK3CA
and
TP53
in aSCCA which is consistent with prior studies evaluating aSCCA tumor NGS in tissue-based assays. Alterations varied across age and sex.
PIK3CA
E545K and E542K alterations were detected frequently in this population and have on-label therapies for non-aSCCA indications which may be a source for clinical consideration in this cancer type in the future. This data illustrates the importance of liquid biopsy NGS to also screen for clinical trial enrollment in a disease which is poorly responsive to standard therapy. Additional research is warranted to further elucidate genomic profiles for clinical applications of this rare tumor.
Incidence and survival trends in small bowel adenocarcinoma (SBA) from 2000-2019 in the United States.
Authors: Sears James Jerod , Xu Yifei , Liu Jingxia , Fiala Mark Aaron , McWilliams Robert R. , Overman Michael J. , Pedersen Katrina Sophia
Published: January 2025

801

Background:
SBA is a rare, poorly understood gastrointestinal malignancy. Adenocarcinomas are often grouped with other small bowel cancer histologies in epidemiologic and outcomes reports, which limits the ability to detect SBA-specific trends. Recent studies in European populations show increasing SBA incidence, but there are limited published data in American cohorts. Identifying trends in SBA can improve understanding of the population most at risk for developing SBA. This study describes U.S. trends in SBA incidence and outcomes from 2000 to 2019.
Methods:
Using the 2022 SEER research-limited dataset, we identified SBA cases and measured the incidence change from 2000-2019. We built linear regression models to evaluate changes in annual incidence by groups, including sex, race, and age of diagnosis, separately. We then compared the overall incidence and trends between subgroups. We investigated overall survival (OS) through the SEER research case listings for SBA patients diagnosed during the study period.
Results:
An average of 0.67 cases/100,000 SBA cases were reported annually from 2000-2019, with a median diagnosis age of 69 years. SBA incidence has increased annually by 0.3% per year from 2000-2019 (p=0.05). From 2000-2019, men were at a higher risk for SBA compared to women (p=0.02). In men, SBA cases increased at a rate of 0.004 cases/100,000/year from 2000-2019 (p=0.01) and a nonsignificant decrease in women of 0.00012 cases/100,000/year. There were no statistically significant differences in incidence or the change in incidence of SBA by race. The age-adjusted incidence was significantly higher each year between 2000 and 2019 in the > 70 cohort compared to the <70 cohort (p=0.02). Cases of SBA increased at a rate of 0.02 cases/100,000/year in adults >70 years (p=0.02). There were no differences in incidence rates in patients <70 years. There was no significant difference in OS for patients diagnosed with SBA in 2000, 2005, 2010, 2015, and 2019 (p=0.21).
Conclusions:
The overall annual incidence of SBA is increasing in the U.S. population. The most significant rate increases are in men and adults older than 70. In the SEER population, trends in SBA contrast with the recent rise of colorectal cancer in the young adult population, highlighting the unique nature of SBA compared to other gastrointestinal malignancies. Additionally, survival outcomes in patients diagnosed with SBA have remained stable over the past 20 years, while other malignancies have shown improvement in the same period. The small cohort size and the lack of a universal U.S. cancer registry limited this evaluation. Improved reporting of SBA cases and further research to identify risk factors are urgently needed to reduce the growing impact of SBA.
Adequate racial and ethnic representation in cancer clinical trial enrollment: Real-world evidence from an NCI-designated cancer center in a minority-majority county.
Authors: Dayyani Farshid , Mahadevan Aditya , Azizi Armon , Valerin Jennifer Brooke , Mar Nataliya , Jeyakumar Deepa , Lee Frank
Published: January 2025

803

Background:
Despite strides to increase diversity in clinical trial enrollment, significant racial and ethnic disparities persist. This limits the generalizability of clinical trial data and consequently the application of novel therapeutics for diverse populations. We hypothesized that enrollment of underrepresented minorities (URM) is feasible, with improved access to clinical care and a tailored clinical trial portfolio addressing the unmet needs in URM.
Methods:
A retrospective cohort study was conducted at the University of California Irvine Chao Comprehensive Cancer Center (CFCCC), an NCI-Designated cancer center located in Orange County (OC), CA (a minority-majority county). Clinical trial enrollment data from 2015-2023 through the CFCCC clinical research database was included. Collected data on patient demographics, tumor types, and trial enrollment was compared to data provided by the NIH SEER reports in both OC and United States.
Results:
Between 2015-2023, 2317 subjects were enrolled in clinical trials at CFCC. Demographics were as follows: White, Asian, Black, American Indian/Alaska Native, mixed/unknown race (66.4%/20.1%/2.4%/0.7%/0.7%/9.3%). Non-Hispanic vs Hispanic ethnicity (77.8%/20.5%). Female vs Male sex (47.6%/52.3%). Age <70 vs >70 years (73.3%/26.7%). Study Phase: Phase I/II (35.6%), Phase II (25.4%), Phase II/III (2.8%), Phase III (26.6%), and Phase IV (0.3%). Study sponsor: Industry (61.1%), Institutional (23.6%), National (14.8%), and Externally Peer Reviewed (0.3%). Most notably, the Asian enrollment (20.1%) and Hispanic enrollment (20.6%) exceeded demographic representation of Asians (17%, RR 1.18) and Hispanics (19%, RR 1.07) at CFCCC. Lastly, Asian patients enrolled at significantly higher rates in lung and liver cancer trials, while Hispanic patients and Black patients enrolled at higher rates in breast cancer and prostate cancer trials respectively.
Conclusions:
Our results demonstrate that robust URM clinical trial enrollment, particularly among Asian and Hispanic populations, is feasible at an NCI-designated cancer center despite minority-specific barriers. These findings suggest that minority populations can be optimally enrolled in clinical trials when these trials are accessible and tailored to the population at hand. Further research is necessary to investigate factors that influence clinical trial participation in the pursuit of equitable cancer care.
Racial disparities in cancer stage at diagnosis among older adults with gastrointestinal cancers in the southeastern United States.
Authors: Doshi Apoorva , Williams Grant Richard , Giri Smith
Published: January 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 < 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 < 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%)
<0.05

Stage II
236 (19%)
57 (13%)

Stage III
321 (25%)
129 (29%)

Stage IV
572 (45%)
210 (47%)
Provider perspectives on non-medical barriers to GI cancer care at a regional cancer center.
Authors: Lal Trisha , Hoehn Richard , Boutros Christina , Kathardekar Anand , Winter Jordan Michael
Published: January 2025

807

Background:
Disparities in care for patients with gastrointestinal (GI) cancers are well-documented, but solutions remain elusive. Understanding the barriers faced by healthcare providers is essential to improving care equity. This study explored the perceptions of healthcare providers at a regional academic health system regarding barriers to care for GI cancer patients.
Methods:
A cross-sectional survey was conducted among healthcare providers, including physicians, advanced care providers (APPs), nurses, dietitians, social workers, care coordinators, and physical/occupational therapists who directly care for patients with GI malignancies. Survey items assessed specific barriers encountered in clinical practice and suggestions for improving care. Descriptive statistical analysis evaluated the quantitative data from the closed-ended questions across professional roles. A thematic analysis was performed on open-response items and assessed to further identify key barriers to care based on respondents' clinical roles and experiences.
Results:
Seventy-nine healthcare providers responded to the survey. Initial treatment planning was consistently identified as the phase with the most significant barriers across all disciplines. Health literacy was cited as the most critical barrier to diagnosis, while insurance coverage, financial constraints, geographic location, lack of transportation, and social support were the primary obstacles to treatment. The importance of these barriers varied by profession: physicians noted geographic and transportation limitations, while nurses and social workers emphasized gaps in health literacy, insurance, and social support. Systemic issues such as limited access to specialized care and healthcare personnel shortages were also noted. Notably, 55% of physicians spent 10-30% of their time addressing non-medical barriers to treatment, while 38% of nurses spent 30-50%. Care coordination across disciplines was commonly cited as a challenge, with many calling for improved communication and establishing multidisciplinary clinics. Food insecurity, housing stability, and language/cultural barriers were less prominent concerns at this institution.
Conclusions:
Oncology providers at a large regional cancer center spend significant time addressing non-medical barriers to treatment for GI cancer patients, particularly during initial treatment planning. The most common challenges reported were insurance, transportation, health literacy, and social support. We will use these findings to guide in-depth provider and patient interviews and develop a team-based, equity-focused intervention. These efforts aim to improve care delivery at our institution and serve as a model enhancing GI cancer care in broader healthcare settings.
Rate of gene fusion/rearrangement identification in GI cancers as sequencing evolved from limited panels to whole exome sequencing.
Authors: Chan Hilary , Thomas Sachdev P. , Jiang Chen , Chung Elaine , Arora Amit , Li Grace , Habel Laurel A.
Published: January 2025

809

Background:
Gene fusion/rearrangements occur at a frequency of 0-15% in GI system cancers. Detection and treatment of fusion genes such as NTRK, FGFR2, NRG1 and RET fusions are included in NCCN guidelines and are commonly detected using next generation sequencing (NGS). NGS panels have continued to expand over time, which should result in increases in the identification of gene fusions. The aims of this study were to describe the percent of patients with advanced GI tumors undergoing NGS with identified gene rearrangements across time as panels expanded.
Methods:
The study included 7237 patients in the Kaiser Permanente Northern California Integrated Health System receiving care for advanced GI cancers from 2017 to Aug 2024, whose tumors samples were evaluated using NGS (Stomach=926, Colorectal=2792, Gallbladder=569, Esophagus=761, liver=218, Pancreas=1971).
Results:
A total of 231 patients (3.2%) were identified with a gene rearrangement, including 4.6% in stomach(N=43), 2.8% in colorectal(N=78), 8.9% in gallbladder(N=24), 5.3% in esophagus(N=40), and 1.9% in pancreatic (N=38
). Rearrangements included NTRK1/2/3, FGFR2/3, NRG, ALK, ROS, CLDN18-ARHGAP, RSPO2/3, DNAJB1-PRKACA, BRAF, MET and RET.
The numbers per year were (see table).
Conclusions:
The use of more comprehensive NGS panels such as WES did not appear to increase the detection rate for fusion/rearrangements. In resource limited settings, limited panels may suffice. The number of GI cancer patients getting NGS testing has increased over time.

Gene rearrangements/fusions identified per year.

YEAR
2018
2019
2020
2021
2022
2023
2024 (Jan – Aug)

Gene Rearrangement identified
29
37
43
55
54
62
38

TOTAL GI Cancer Samples Sequenced
610
858
900
1047
1249
1181
785

Percentage
4.75%
4.31%
4.78%
5.25%
4.32%
5.25%
4.84%
Treatment patterns in patients with advanced gastrointestinal stromal tumor in Japan: An administrative claims database study.
Authors: Komatsu Yoshito , Naito Yoichi , Hirano Yuko , Kunitomi Yuji , Takahashi Tsuyoshi
Published: January 2025

811

Background:
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract. Tyrosine kinase inhibitors, including imatinib, sunitinib, and regorafenib, and the HSP90 inhibitor, pimitespib have been approved for advanced GIST in Japan, but few studies have examined the nationwide trend in treatment patterns. This study aimed to evaluate the real-world treatment patterns for advanced GIST in Japan.
Methods:
This retrospective cohort study used the Japanese hospital-based administrative claims database provided by Medical Data Vision Co., Ltd. (Tokyo, Japan). Patients diagnosed with advanced GIST according to ICD-10 codes who received any approved standard drug in Japan, such as imatinib, sunitinib, regorafenib, or pimitespib (Approved in June 2022) between July 2013 and March 2023 were included. The primary endpoint was the proportion of patients with GIST who were treated with each approved standard drug. Secondary endpoints included treatment patterns, time to treatment failure (TTF), overall survival, adverse events, and the proportion of patients who underwent surgical intervention for GIST while taking standard drugs.
Results:
This study included 2702 patients with advanced GIST. The median age was 70.0 years, 17% of the patients were ≥80 years, and 59% were male. The most common primary tumor sites were the stomach (37%), small intestine (25%) and large intestine (12%). The proportions of patients with GIST treated with imatinib, sunitinib, regorafenib, and pimitespib were 94% (2536 patients), 26% (702 patients), 14% (376 patients) and 1% (37 patients), respectively. The most common first-line regimen was imatinib (2485/2702 patients; 92%), second-line regimen was sunitinib (560/672 patients; 83%), third-line regimen was regorafenib (200/317 patients; 63%), and fourth-line regimen was imatinib (55/119 patients; 46%). The median TTF was 30.4 months (95% CI 27.4–32.9) with imatinib, 6.4 months (95% CI 5.6–7.7) with sunitinib, 5.2 months (95% CI 4.4–6.2) with regorafenib and 2.5 months (95% CI 1.7–3.1) with pimitespib. The proportions of patients who underwent surgical intervention for GIST was 15% (403/2702 patients), and curative surgery was 10% (273/2702 patients).
Conclusions:
This is the first real-world study to provide insights into the patient characteristics and current treatment patterns for advanced GIST in Japan. The treatment patterns are consistent with the Japanese Clinical Practice Guidelines.
Current status and treatment outcomes of intraductal papillary mucinous carcinoma in Korea: A multi-center cohort study.
Authors: Lim Hee-Eon , Lee Jong-chan , Paik Woo Hyun , Lee Yoon Suk , Choi Jin Ho , Park Joo Kyung Sophie , Choi Young Hoon , Lee Kang Won , Lee Jae Min , Kim HyeonKi , Seo Wootaek , Jung Kwangrok , Kim Jaihwan , Hwang Jin-Hyeok
Published: January 2025

812

Background:
The spectrum of intraductal papillary mucinous neoplasm (IPMN) varies from benign cysts to intraductal papillary mucinous carcinoma (IPMC). There is a lack of large-scaled data on IPMC and high-grade dysplasia. We aimed to study the real-world status and treatment outcomes of IPMC in South Korea.
Methods:
This is a retrospective, multicenter study conducted in South Korea. We reviewed the electronic medical records of patients who were histologically diagnosed with IPMC or high-grade (HG) dysplasia between 2011 and 2020, and analyzed the baseline characteristics, treatment patterns, and survival.
Results:
A total of 388 patients were eligible from six institutes (145 female [37%]; median age 67.8; 259 IPMC [67%] vs 129 HG dysplasia [33%]). The median overall survival for IPMC patients was 75 months, compared to 133 months for HG dysplasia. In IPMC group, 217 (84%) were underwent surgical resection and 42 (16%) did not underwent surgery due to general condition or advanced stage whose median overall survival was 83 months and 49 months respectively. In resected IPMC, 104 (48%) received adjuvant chemotherapy (gemcitabine single 48%, 5FU+leucovorin 33%, others 19%) and 66 (30%) experienced recurrence and median recurrence-free survival (RFS) was 20 months. Among IPMC group, 11 (4.2%) was in advanced stage and eight of those received palliative chemotherapy (FOLFIRINOX 62.5%; gemcitabine single 25%; gemcitabine with erlotinib 12.5%). In HG dysplasia, 108 (84%) patients underwent surgery, and 21 (16%) patients did not undergo surgery whose OS were 171 and 133 months, retrospectively. In patients with resected HG dysplasia, 29 (27%) experienced recurrence and median RFS was 21 months.
Conclusions:
IPMC generally showed longer survival and a lower recurrence rate than those of historical data in PDAC, with HG dysplasia demonstrating even better outcomes. In real world, similar chemotherapy regimens used for PDAC were applied to IPMN patients.

Treatment status of intraductal papillary mucinous carcinoma and high-grade dysplasia.

IPMC(259)
IPMN-HG(129)
Total(388)

Median overall survival (month)
75
133
85

Treatment OP
217(84%)
108(84%)
325(84%)

Adjuvant chemotherapy
104(48%)
19(18%)
123(38%)

Recurrence rate
66(30%)
29(27%)
95(29%)

Median recurrence-free survival (month)
20
19
21

Palliative chemotherapy
8(3%)
NA

Progression rate
5(63%)
NA

Progression-free survival (month)
13
NA
Surgical treatment in patients with advanced gastrointestinal stromal tumours (GISTs) in second-line and later stages: A single-centre cohort study.
Authors: Zhang Xinhua , Yan Miao , Lu Yi , Sun Kaiyu , Ye Jinning , Wu Hui , Chen Chuangqi , Cai Shirong , He Yulong
Published: January 2025

818

Background:
Gastrointestinal stromal tumour (GIST) after imatinib treatment failure usually progresses rapidly with limited overall survival. Previous studies have suggested that surgery is beneficial for advanced GISTs in disease control to imatinib, but the role of surgery in > = 2 line patients remains unclear.
Methods:
Imatinib-resistant patients with advanced GIST between May 2009 and Nov. 2023 were included. Surgical treatments included tumour reduction, radiofrequency ablation and TACE. The primary endpoint was overall survival (OS) and secondary endpoints were time to second-line treatment failure (TTF) and postoperative morbidity. To balance clinicopathological characteristics, 1:1 propensity score matching (PSM) was used.
Results:
A total of 242 patients with advanced GIST treated with 2nd-line or later drugs were included, including 125 in the surgical group and 117 in the non-surgical group. The median follow-up was 30.3 months. OS was significantly better in the surgical group than in the non-surgical group (pre-PSM: 51.7m vs 35.9m , p = 0.001; post-PSM: 50.8m vs 38.8m, p = 0.043). Univariate analysis showed that surgical treatment (HR 0.487, 95% CI 0.320-0.740, p = 0.001), age ≤60 years (HR 0.640, 95% CI 0.411-0.997, p = 0.049) and low tumour burden (HR 0.491, 95% CI 0.293-0.822, p = 0.007) were associated with prolonged OS. Multivariate analysis indicated that surgical treatment (HR 0.541, 95% CI 0.348-0.843, p = 0.007) and low tumour burden (HR 0.510, 95% CI 0.300-0.865, p = 0.012) were significantly associated with OS benefit. Patients (n = 84) who had surgical treatment during second-line treatment had longer TTF compared to patients (n = 158) who had TKI only (14.2m vs 8.1m , p = 0.003). There were 29 (14.8%) postoperative complications with Clavien-Dindo classification ≥3, including 5 deaths.
Conclusions:
Surgical treatment can provide a survival benefit for patients with second-line and later advanced GIST, but further studies are needed for a more detailed indication of the surgical population.
Phase II trial of sintilimab in cancer of unknown primary.
Authors: Huey Ryan W , Raghav Kanwal Pratap Singh , Estrella Jeannelyn , Higbie Victoria , Le Phat , Bent Alisha Heather , Matamoros Aurelio , Lano Elizabeth A , Willett Anneleis , Nguyen Vincent , Escano Michelle , Wilson Kaye F , Lin Heather Y.
Published: January 2025

825

Background:
CUP is an aggressive rare malignancy accounting for 2-4% of all cancers. Beyond frontline therapy, predominantly systemic cytotoxic chemotherapy, no clear standard of care exists. Preliminary data suggests that immune-checkpoint inhibitors have encouraging activity in patients with CUP. Prior anti-PD1 agents have demonstrated response rates of 21-23%. We studied the role of sintilimab, an anti-PD1 antibody, in CUP.
Methods:
In this phase II study (NCT05024968)10 patients (of planned 40) were enrolled prior to closure of the study due to sponsor funding. Patients were eligible if they were refractory or intolerant to one line of systemic therapy or had a contraindication for cytotoxic chemotherapy. Patients received sintilimab 200 mg IV every 3 weeks. Paired tumor biopsies were collected for biomarker analysis. The primary endpoint was confirmed objective response rate (cORR) by RECISTv1.1 assessed by independent radiology review. Key secondary endpoints were safety, disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and Quality of Life (QOL). Median PFS and OS were calculated according to the Kaplan-Meier method. Adverse events (AEs) were assessed according to CTCAE v5.0.
Results:
Between 10/2021 and 2/2023, 10 patients were enrolled and treated. Median age was 65 years and 30% of patients were female. Seven (70%) had poorly differentiated carcinoma. Patients received a median of 1 line of therapy prior to enrollment. Median follow-up was 19.8 months. All patients were evaluable for toxicity and response. The cORR was 40% (95% CI, 12.2 to 73.8); one (10%) patient with a complete response and 3 (30%) with partial responses. The median DOR was 15.7 months. Three patients (30%) had Grade ≥ 3 (no grade 4/5) treatment-related AEs including 2 patients with sepsis and 1 patient with leukocytosis. Median PFS and OS were 4.4 months (95% CI, 2.0 to 25.4) and 25.4 months (95% CI, 4.0 to 27.4), respectively.
Conclusions:
Anti-PD1 therapy with Sintilimab demonstrated significant anti-tumor activity for select patients with refractory CUP with safety profile consistent with other anti-PD1 agents. Ongoing correlative studies may inform the role of biomarker selection for immunotherapy in CUP.
Clinical trial information: NCT05024968
.
AGX101: A TM4SF1-directed tubulin inhibitor conjugate in ongoing first-in-human trial including GI cancers.
Authors: Jaminet Paul , Rodriguez Rivera Ildefonso I , Jaminet Shou-Ching , Weiss Glen J. , Pelster Meredith
Published: January 2025

829

Background:
TM4SF1 (Transmembrane-4 L-Six-Family-Member-1) is an endothelial marker with critical roles in angiogenesis, as well as a tumor cell antigen that contributes significantly to invasion and metastasis. TM4SF1 is upregulated 20-fold in angiogenic tumor vascular endothelium compared to normal vasculature endothelium and exhibits a unique nuclear internalization pathway. AGX101 is a novel tubulin inhibitor conjugate specifically directed against TM4SF1, delivering a potent maytansinoid payload directly to the nucleus of cells within the tumor microenvironment. Delivery to both the vascular and tumor cell compartments of the tumor results in three mechanisms of action (MoAs): (1) activation of tumor immune surveillance, (2) tumor blood supply deprivation, and (3) direct tumor cell killing.
Methods:
TM4SF1 expression was assessed using immunohistochemistry. Safety and pharmacokinetics of AGX101 were evaluated in non-human primates (NHP), with escalating doses to determine the highest non-severely toxic dose (HNSTD). Efficacy studies were also conducted in mouse models, enabling assessment of the minimum effective dose (MED) needed to engage each of the three MoAs. The combination of HNSTD and MED enables calculation of a therapeutic index (TI). The potential for synergy with immune checkpoint inhibitors (ICIs) was also investigated. A first-in-human study of AGX101 in patients with advanced solid tumors with the primary objective of safety and dose-limiting toxicities (DLTs) has initiated.
Results:
Notable cancers with high TM4SF1 scoring intensity include pancreatic adenocarcinoma, hepatocellular carcinoma, cholangiocarcinoma, and gastric cancer. In esophageal cancer, 20% of patients have a TM4SF1 copy number amplification, and these have worse prognosis. In NHP, AGX101 exhibited a favorable safety profile. In preclinical efficacy studies, monotherapy demonstrated robust efficacy through each of the three MoAs in syngeneic models in mice including CT26 colon carcinoma, and human tumor xenograft models including MIA PaCa-2 pancreatic cancer. Measured by exposure, TI was large. In syngeneic mouse models including CT26, the effects of ICIs were potentiated, suggesting a potential synergistic approach in cancer therapy. The first two dose levels of AGX101 monotherapy in humans has cleared without DLTs. Three patients with pancreatic adenocarcinoma have been treated thus far.
Conclusions:
AGX101, targeting the TM4SF1 antigen, represents a promising new approach in cancer therapy. The preclinical data suggest that AGX101 could provide a significant therapeutic benefit by novel and differentiated mechanisms of action, namely selectively targeting the tumor vasculature and potentiating immune-based therapies. Further clinical development of AGX101 is ongoing and initial outcome data will become available by the conference.
Clinical trial information: NCT06440005
.
Personalised use of repurposed non-anticancer drugs in colorectal cancer based on up-regulated signalling pathways: A real world cohort feasibility study.
Authors: Gaya Andrew M. , Patil Darshana , Datta Vineet , Srivastava Navin , Apurwa Sachin , Akolkar Dadasaheb B , Shreenivas Aditya V.
Published: January 2025

833

Background:
Targeting signaling pathways in colorectal cancers is a common therapeutic strategy. In addition to targeted drugs, non- anticancer drugs approved for use in other health conditions can inhibit key pathways. De novo tumor transcriptome analysis can identify patient-specific up- and down-regulated transcripts, based on which the corresponding repurposed drugs can be used in synergistic combinations with standard of care (SoC) regimens.
Methods:
This retrospective study was conducted on a real-world cohort of 459 colorectal cancer cases (218 females, 241 males; median age 56 years) who had taken Exacta multi-omics tumor profiling for selection of personalized treatments. Transcriptome analysis was performed as part of the evaluations to determine up and down-regulated gene transcripts for selecting targeted, endocrine, and cytotoxic anticancer agents as well as non-anticancer (repurposed) drugs and phytochemicals that could be used for tandem targeting of the dysregulated signaling pathways, as indicated in the table below.
Results:
Transcriptome analysis of this cohort revealed dysregulation of ≥1 pathway in 391 patients (85.2%). MAPKs (n = 244, 53.2%) and MMPs (n = 210, 45.8%) were most frequently upregulated. Celecoxib (n = 292, 63.6%), Atorvastatin (n = 255, 55.6%), and Doxycycline (n = 208, 45.3%) were the most frequently indicated repurposed drugs for targeting the identified dysregulated pathways. Potential indications for ≥1 repurposed drugs were seen in 353 patients (76.9%).
Conclusions:
Several cellular signaling pathways are known or potential therapeutic targets in cancers. The present study indicates that it may be possible to use multi-omics analyses to create personalized treatment strategies using a synergistic combination of repurposed drugs to potentiate the action of SoC systemic anticancer agents in colorectal cancer.

Biomarkers for non anti-cancer drugs selection.

Drug
Biomarker/Gene Expression

Aspirin
PTGS2 (COX2)

Atorvastatin
HMGCR, MAPK

Bromelain
PTGS2 (COX2)

Celecoxib
PTGS2 (COX2), FZD, WNT, ΜΑΡΚ

Chloroquine
HMGB1

Curcumin
MMP, BIRC5, BCL2

Doxycycline
MMP

Metformin
MMP, BCL2, ΜΑΡΚ

Quercetin
FZD, WNT

Resveratrol
MMP, BCL2, PCNA, PTGS2 (COX2)

Vitamin C
SLC2A1 (GLUT1)

Artesunate
FZD, WNT, MMP, BCL2

Cannabidiol
MMP

Epigallocatechin gallate
MMP, MAPK

Mebendazole
XIAP, MMP, MAPK
Characterization of the tumor immune microenvironment (TIME) and somatic landscape in gastrointestinal (GI) malignancies with
MTAP
deletions (del).
Authors: Gong Jun , Ciombor Kristen Keon , Valerin Jennifer Brooke , Huang Minxuan , Williams Edward , Stoppler Melissa Conrad , Mercer Jacob , Strickler John H
Published: January 2025

835

Background:
PRMT5 is a synthetic lethality target in patients (pts) with
MTAP
del and early phase trials are underway with PRMT5 inhibitors. Additionally,
MTAP
del are associated with a less immunogenic TIME and reduced efficacy of immunotherapy, but research has primarily not been focused on GI malignancies. Thus, we investigated the TIME and somatic landscape in GI malignancies with
MTAP
del.
Methods:
From the Tempus Database, we retrospectively analyzed de-identified next-generation sequencing data from pts across GI malignancies, including pancreatic (n=11,217), gastroesophageal (GEJ, n=5,803), cholangiocarcinoma (CCA, n=3,244), and colorectal (CRC, n=17,537) cancers. Tumors were sequenced with the Tempus xT DNA (648-gene panel) and xR RNA assays.
MTAP
del were defined as two-copy losses. Somatic alterations (alt), immune cell infiltration predicted from gene expression patterns, PD-L1 from IHC, TMB, and MSI were evaluated. Chi-squared/Fisher’s Exact tests or Kruskal-Wallis tests were used to assess statistical significance (p<0.05, q<0.05 for false discovery rate correction for multiple testing).
Results:
MTAP
del were identified in 14.8%, 11.3%, 0.9%, and 7.3% of pancreatic, CCA, CRC, and GEJ cancers, respectively. Of these, 98/93%, 99/91%, 92/89%, and 98/89% had co-occurring
CDKN2A/B
loss. In pancreatic, CCA, and CRC pts,
MTAP
del was associated with a reduced proportion of B cells and CD4 T cells, and there were higher percentages of macrophages vs pts with
MTAP
WT status (p<0.001 for all). Reductions in proportion of CD8 T cells were also associated with
MTAP
del in pancreatic and CCA pts (p<0.001 for both). Lower TMB (p=0.036) and MSI-H status (p=0.009) were found in CRC pts with
MTAP
del. GEJ with
MTAP
del also exhibited significantly lower MSI-H status than
MTAP
WT GEJ (p=0.014).
SMAD4 alterations
, a marker of reduced immune infiltrates, were more prevalent in pts with
MTAP
del across GI malignancies (q<0.005). In the CCA cohort, there was a higher percentage of
BRAF
alt and FGFR2 fusions in pts with
MTAP
loss (q<0.001, q=0.028), while
KRAS
alt were higher in pancreatic cases with
MTAP
loss (q<0.001).
Conclusions:
This is the largest analysis of the TIME and somatic landscape of
MTAP
loss across GI malignancies. In pts with
MTAP
del and pancreatic cancer, CCA, and CRC, we observed a less immunogenic TIME pattern, indicating the evaluation of immunotherapy implications in these GI malignancies with
MTAP
del is warranted. Our findings are hypothesis-generating, providing further rationale to study synthetic lethality and novel combinatorial therapeutic strategies in GI malignancies with
MTAP
del.
Use of gene expression profiling to examine association between MUC1 and claudin 18 in gastrointestinal cancers: Implications for targeted therapies.
Authors: Shreenivas Aditya V. , Gaya Andrew M. , Shaikh Muzammil , Vora Amish , Shingla Shivam , Kulkarni Shriniwas Subhash , Ajami Ramin , Akolkar Dadasaheb B , Schuster Stefan , Datta Vineet , Patil Darshana , Apurwa Sachin , Datar Rajan , Limaye Sewanti Atul
Published: January 2025

838

Background:
Gastrointestinal tract cancers exhibit considerable molecular heterogeneity, which requires a detailed understanding of their distinct genetic profiles. Understanding the gene expression of other genes along with Claudin 18 (CLDN18) could provide insights into their interactions.
Methods:
We conducted a retrospective analysis of NGS profiling on 1,043 GI cancer tissue samples from three cohorts: Upper and Lower Gastrointestinal Cancer Cohort (GICC; n=651), Pancreaticobiliary Cancer Cohort (PBCC; n=316), and Hepatocellular Carcinoma Cohort (HCC; n=76). Immunohistochemistry data for PD-L1, Her2 and MMR proteins, NGS based Tumor mutation burden (TMB) and gene expression profiling (GEP) of 20,802 genes including CLDN18 was examined in a subset by targeted transcriptome profiling. We explored associations of these biomarkers with expression of CLDN18.
Results:
In GICC, frequent mutations were seen in TP53 (68%; 442), APC (33.5%; 218) and KRAS (33.3%; 217). PBCC, showed mutations in TP53 (62%; 197), KRAS (47%; 149) and CDKN2A (16%; 51). HCC showed mutations in TP53 (42%; 32), ARID1A (18%; 14) and KRAS (9%; 7). Amplifications were predominantly observed in MYC (13%; 120), ERBB2 (5%; 49) and CCND1 (5%; 44). Fusions were infrequent. All MSI-H cases (11/462; 2.4%) were observed in GICC. High TMB (≥10 muts/mb) was seen in 23% (111/481), stratified as 28% (90/318) in GICC, 13% (18/139) in PBCC and 10% (3/30) in HCC. Out of 321 samples analyzed for gene expression profiling, CLDN18 was significantly upregulated in 65 (20%) samples. The expression of CLDN18 did not show statistically significant correlation with Her2 (n=184), PD-L1 (n=231), TMB (n=228), or MSI (n=229); (p>0.05). In subset where both CLDN18 and MUC1 expression were analyzed (n=118), all the CLDN18 positive tumors showed overexpression of MUC1. This finding was statistically significant (p<0.05). Increased expression of MUC1 promotes cancer cell mobility promoting metastases. Expression of MUC1 can play an important role in the development of resistance to chemotherapy. MUC1 expression in cancer cells is associated with avoidance of immune defenses. Thus, this finding of CLDN18 and MUC1 association is especially relevant as the CLDN18 targeted therapies may be the potential avenue for the aggressive and chemo-resistant MUC1 expressing tumors.
Conclusions:
This study identifies potential association between MUC1 and CLDN18. GEP could enhance biomarker detection and support personalized treatment approaches. Future research should integrate these findings with clinical data to improve precision in GI cancer care.
Can an alteration of the gut microbiome increase risk of gastrointestinal malignancies? Insights from the National Inpatient Sample.
Authors: Lohani Sweta , Baskar Suriya , Desai Chaula , Khan Fiqe , Midha Rajiv , Baskar Udhaya , Vasikaran Anush
Published: January 2025

841

Background:
The gut microbiome is composed of trillions of microorganisms, inhabiting the lining of the gastrointestinal (GI) tract. The gut microbiome plays multiple roles in upholding human health including maintaining metabolism and regulating immune homeostasis. Dysregulation of the gut flora is known as gut dysbiosis. Studies have shown that gut dysbiosis is linked to the development of malignancies such as colorectal cancer. The purpose of this study is to assess the correlation between an altered gut flora and development of GI malignancies.
Methods:
The National Inpatient Sample was queried between 2016-2020 for all adult patients with altered gut flora, defined by history of gastrointestinal/bariatric surgeries, history of clostridium difficile infection, long-term antibiotic use, and inflammatory bowel disease. Rates of various cancers were compared between this cohort and all other patients utilizing chi-squared tests. Binary logistic regressions were utilized to calculate odds ratios of developing the various cancers, adjusted for age, sex, Charlson Comorbidity Index (CCI), and smoking status.
Results:
A total of 7,758,168 hospitalizations with altered gut flora were identified. Esophageal cancer (aOR 3.16, 95% CI 3.08 - 3.24) and colorectal cancer (aOR 3.15, 95% CI 3.11 - 3.18) were observed to have the highest odds of occurring in patients with altered gut flora. Gastric, hepatobiliary, pancreatic, and neuroendocrine cancers also all had significantly higher odds of occurring in patients with altered gut flora.
Conclusions:
Our study shows that conditions altering the gut flora are associated with increased odds of malignancies of the GI tract. This suggests that the gut microbiome may play an intricate role in regulation of tumor cell proliferation. Optimization of gut health and restoration of gut flora may prove beneficial to patients at high risk for malignancies of the GI tract.

Altered Gut Flora (%)
Intact Gut Flora (%)
Adjusted Odds Ratio (CI)
p-value

Esophageal
0.4
0.1
3.16 (3.08 - 3.24)

<.001

Gastric
0.3
0.1
1.67 (1.64-1.69)

<.001

Colorectal
2.5
0.6
3.15 (3.11 - 3.18)

<.001

Hepatobiliary
0.4
0.3
1.04 (1.02 - 1.07)

<.001

Pancreatic
0.6
0.3
1.34 (1.31 - 1.37)

<.001

Neuroendocrine
0.2
0.1
1.38 (1.33 - 1.44)

<.001