bluuebunny/crossref_metadata_2025 huggingface dataset:
Preliminary safety and efficacy of upfront FOLFOXIRI and bevacizumab with cadonilimab in patients with proficient mismatch repair/microsatellite stable (pMMR/MSS) metastatic colorectal cancer: A multicenter phase II study (SYLT-026).
Authors: Lin Rongbo , Chen Luchuan , Yang Chunkang , Guo Zengqing , Zhao Shen , Su Liyu , Yang Xianghua
Published: January 2025

198

Background:
The AtezoTRIBE phase II trial reported that adding Atezolizumab to upfront FOLFOXIRI plus Bevacizumab significantly improved overall survival (OS) in patients with metastatic colorectal cancer (mCRC). However, the improvement in OS was modest within the pMMR/MSS subgroup (HR, 0.80 [80% CI, 0.63–1.02]; P = 0.117) [1]. Cadonilimab, a humanized bispecific antibody targeting both PD-1 and CTLA-4, may offer enhanced therapeutic benefits. Therefore, this study aims to investigate whether the addition of Cadonilimab to upfront FOLFOXIRI plus Bevacizumab improves efficacy while maintaining safety in patients with pMMR/MSS mCRC.
Methods:
This multicenter, single-arm phase II study enrolled treatment-naive patients with pMMR/MSS mCRC, aged 18–75, who had at least one measurable lesion according to RECIST 1.1, an ECOG performance status (PS) of 0–2, and adequate organ function. Patients with dMMR/MSI-H tumors or prior immunotherapy were excluded. Eligible participants received FOLFOXIRI (irinotecan 165 mg/m², oxaliplatin 85 mg/m², leucovorin 200 mg/m², and fluorouracil 2400 mg/m² as a 48-hour infusion), along with Bevacizumab (5 mg/kg), and Cadonilimab (6 mg/kg). Treatment was administered for up to twelve 14-day cycles, followed by maintenance therapy with fluoropyrimidine and Bevacizumab plus Cadonilimab for up to 52 weeks, or until disease progression, unacceptable toxicity, or withdrawal of consent. Patients were equally enrolled, with 10 having liver metastases and 10 without. The primary endpoint was objective response rate (ORR) per RECIST 1.1.
Results:
As of August 30, 2024, 20 patients were enrolled, with a median age of 65.5 years (range: 33–74). Of these, 40% had an ECOG PS of 1 or 2, 55% had three or more metastatic organs, and 7 patients (35%) had RAS or BRAF mutations. The median follow-up was 5.0 months. Fifteen patients underwent at least two imaging assessments, revealing a confirmed ORR of 100% (15/15) and a disease control rate (DCR) of 100%. The median progression-free survival (PFS) and OS data were not yet mature. All 20 patients experienced treatment-emergent adverse events, most of which were grade 1 or 2. One patient (5%) discontinued treatment due to immune-mediated colitis. The most common grade 3/4 adverse events included neutropenia (55%), leukopenia (15%), infusion reactions (5%), dermatitis (5%), colitis (5%), anemia (5%), elevated ALT (5%), and diarrhea (5%). No new safety signals were identified.
Conclusions:
In conclusion, Cadonilimab in combination with FOLFOXIRI and Bevacizumab demonstrated promising efficacy and a manageable safety profile as a first-line treatment for patients with pMMR/MSS mCRC. Further investigation in larger trials is warranted. 1. Antoniotti, et al, J Clin Oncol, 2024.
Clinical trial information: NCT05839470
.
Incidence trends of early-onset colorectal cancer (EOCRC) in the United States, by age, sex, race and ethnicity, and urbanicity (2000-2021).
Authors: Van Blarigan Erin , McKinley Meg A. , Finster Laurel J. , Cheng Iona , Gomez Scarlett L. , Haile Robert
Published: January 2025

26

Background:
Research is needed to understand the extent to which the incidence of early onset colorectal cancer (EOCRC)is rising across population sub-groups, including by age, sex, race/ethnicity, and urbanicity, to inform hypotheses regarding its causes and strategies for screening and prevention.
Methods:
We used data on colorectal cancer cases diagnosed among adults 20-49 years (yr) between 2000-2021 in the delay-adjusted Surveillance, Epidemiology, and End Results (SEER) database (April 2024). We calculated delay- and age-adjusted annual incidence rates (IR) per 100,000, overall and by age, sex, race/ethnicity, and urbanicity. Urbanicity was defined using USDA Rural-Urban Continuum Codes for county; 1-3 were classified as urban and 4-9, 98, and 99 were classified as non-urban. We used NCI’s Joinpoint regression models (Joinpoint version 5.2.0.0) to estimate annual percent change (APC) and 95% confidence intervals (CI). We also calculated IRs for the most recent 5-year period (2017-2021) and used incidence rate ratios (IRR) to compare across groups; IRs and IRRs were calculated using SEER*Stat version 8.4.3.
Results:
Analyses included 155,500 cases of EOCRC. Most cases (72%) occurred among adults 40-49 yr; 22% occurred among those 30–39 yr and 6% in people 20-29 yr. Among adults 40-49 yr, the incidence of EOCRC increased 4.4% / yr on average between 2018-2021 (95%CI: 2.5, 5.6). Among adults 30-39 yr, incidence of EOCRC increased 3.0% / yr, on average, starting in 2010 (95%CI: 2.4, 4.5). For adults ages 20-29 yr, there were large increases in incidence from 2000-2016 (2000-2013, APC: 3.5; 95%CI: 2.4, 4.1; 2013-2016, APC: 11.2; 95%CI: 6.8, 13.5) but no change from 2016-2021. For the most recent 5-yr period (2017-2021), females had lower IR compared to males (IRR: 0.90; 95%CI: 0.88, 0.91), but trends over time were similar by sex. The incidence of EOCRC increased across races and ethnicities between 2000-2021, albeit at different rates. In the most recent period (2017-2021), the IR per 100,000 was 22.0 for Non-Hispanic American Indian and Alaskan Native (AIAN), 15.0 for Non-Hispanic White, 14.9 for Non-Hispanic Black, 12.4 for Hispanic or Latino, and 11.2 for Non-Hispanic Asian American or Pacific Islander adults. People in non-urban areas had a higher incidence of EOCRC compared to those in urban areas (IRR: 1.18; 95%CI: 1.14, 1.22), with similar trends over time.
Conclusions:
The incidence of EOCRC is highest among adults 40-49 yr, males, Non-Hispanic AIAN adults, and in non-urban areas. Trend analyses generally showed similar increases in incidence (3-5%/yr) in recent periods across sex, race/ethnicity, and urbanicity.
Landscape of novel gene fusions in gastrointestinal tumors.
Authors: Balyimez Aysegul , White Karen L , Hoag Jess R , Starodynov Arthur , Alyaqoub Fadel S. , Noel Pawan , Li Shoudong , Basu Gargi D. , De La O Jean-Paul , Kemkes Ariane C.
Published: January 2025

268

Background:
Gene fusions are recognized as critical drivers of cancer and targets for precision therapies. The 2022 ASCO provisional clinical opinion on tumor genomic testing includes recommendations for fusion testing and recognizes the strengths of RNA-based approaches. Targeted DNA/RNA sequencing panels can be used to detect well characterized, clinically actionable fusions, but their ability to detect rare novel fusions (i.e., those with uncharacterized fusion partners) can be limited by assay design. Whole-exome, whole-transcriptome sequencing (WES/WTS) may improve the identification of actionable gene fusions by detecting both known and novel fusions. This work describes clinically actionable novel fusions detected in gastrointestinal (GI) cancers.
Methods:
The study included samples from GI cancers that were analyzed using the OncoExTra test between May 2018 and May 2024. The assay uses tumor-normal WES/WTS to identify somatic alterations, including gene fusions with known and unknown partners and breakpoints.Clinical data were queried foractionable fusions with novel fusion partners that were unique in the entire laboratory database and have not, to our knowledge, been previously reported in the existing scientific literature or public databases. Actionable fusions were defined as those associated with FDA-approved targeted therapies or those that made patients eligible for a clinical trial.
Results:
Tumor samples from 2,776 patients with GI cancers were evaluated with a total of 75 actionable fusions identified in samples from 74 patients. Of these, 25.3% (n=19) were novel, and 74.7% (n=56) were previously described or recurrent fusions. Novel fusions were detected in small bowel (2 of 81), colorectal (4 of 1,621), gastric/gastroesophageal junction (GEJ) (2 of 259), pancreatic (7 of 466) and biliary (4 of 131) cancers. Thirteen (63.2%) of the novel fusions involved genes associated with FDA-approved therapies, including FGFR2 (n=6), BRAF (n=3), MET (n=2), FGFR1 (n=1) and NTRK2 (n=1). Of the fusions associated with FDA-approved therapies, 20% (8/40) of recurrent fusions and 38.5% (5/13) of novel fusions were detected only by RNA sequencing. No fusions were identified in appendiceal or esophageal cancers.
Conclusions:
Gene fusions with novel fusion partners represented one fourth of all actionable fusions detected in GI tumors. Use of a comprehensive WES/WTS testing approach that detects fusions agnostic of the fusion partner may affect clinical care in GI cancers by increasing the number of patients eligible for targeted therapies.
Prediction of immunotherapy response in deficient mismatch repair colorectal cancers using an immune-enhanced exome and transcriptome platform.
Authors: Sinicrope Frank A. , Saberzadeh-Ardestani Bahar , gupta Anupama , Graham Rondell P. , Lewis Jason T , Abbott Charles , Boyle Sean Michael
Published: January 2025

270

Background:
While immune checkpoint blockade (ICB) is used to treat metastatic deficient mismatch repair (dMMR) colorectal cancers (CRCs), such tumors are heterogeneous and resistance to ICB is frequent. To date, biomarkers that can consistently predict patient response to ICB are lacking. We determined whether biomarkers that integrate tumor and immune-related molecular mechanisms could predict ICB response.
Methods:
Consecutive patients with metastatic dMMR CRCs (N=32) who had been treated with anti-PD-1 therapy were proﬁled using a validated immune-enhanced exome and transcriptome platform (ImmunoID NeXT, Personalis) using tumor and paired normal tissue. This platform provides antigen-specificity of T or B cells, indicated by the TCR or BCR respectively, neoantigen prediction, tumor mutation burden (TMB), immune profile, HLA allele-speciﬁc loss of heterogeneity (LOH) and a Neoantigen Presentation Score (NEOPS) that combines a neoantigen prediction tool with mechanisms of immune evasion. Tumor variables were analyzed in relationship to objective tumor response, and a Cox proportional hazards model was fit to predict progression-free survival (PFS) or overall survival (OS).
Results:
In CRCs, TCR and BCR repertoire diversity were each significantly increased in tumors from responders versus those with stable or progressive disease after anti-PD-1 treatment (p=0.015 and p=0.048, respectively). Neoantigen burden score, TMB, and HLA allele-speciﬁc LOH (reflects loss of antigen presentation machinery) were each unable to distinguish responders from nonresponders. An immune checkpoint gene expression signature was increased in nonresponders relative to responders (P= 0.005). Neoantigen presentation score (NEOPS) was prognostic when adjusted for tumor grade only for OS (p=0.048).
Conclusions:
The T-cell and B-cell receptor (TCR/BCR) repertoire, as well as NEOPS, were each significantly predictive of favorable response to anti-PD-1 therapy in dMMR tumors. In addition, an immune checkpoint gene expression signature was predictive of resistance to ICB.
Exploring the link between liver cirrhosis and liver metastasis in colorectal cancer.
Authors: Desai Chaula , Baskar Suriya , Turku Davin , Lohani Sweta , Vasikaran Anush
Published: January 2025

301

Background:
Colorectal cancer (CRC) is the third most common cancer and the second most common cause of cancer mortality in the world. Although it is now associated with improved outcomes due to advancements in treatment modalities, CRC continues to be the most common source of liver metastasis. Previous studies have shown cirrhotic livers to be at reduced risk of metastatic disease. Our study aims to investigate the association between colorectal cancer and liver metastasis in the presence of concomitant liver cirrhosis.
Methods:
The National Inpatient Sample (NIS) was queried to identify all hospitalizations with colorectal cancer utilizing ICD-10 codes C18.x, C19.x, and C20.x from 2016 to 2020 and were further classified based on the presence or absence of cirrhosis. Demographic and clinical data were analyzed using chi-squared tests, independent sample t-tests, and binary logistic regression (adjusted for age, gender, and Charlson comorbidity index or CCI). The primary outcome studied was liver metastasis. Secondary outcomes were hepatic encephalopathy, portal hypertension, and spontaneous bacterial peritonitis. Statistical significance is indicated by a p-value less than 0.05.
Results:
A total of 255,599 hospitalizations with colorectal cancer were identified. Out of these, 5,370 (2.1%) had liver cirrhosis and 250,229 (97.9%) did not. Hospitalizations with CRC and concomitant cirrhosis had higher comorbidities as per the Charlson Comorbidity Index (10.5 vs 8.1, p-value<0.001) and higher mortality rates (8.5% vs 4.2%, p-value<0.001). Higher rates of liver metastasis (26.5 vs 23.4, p <0.001) and portal hypertension (26.1% vs 0.3%, p<0.001) were observed in the cirrhosis subgroup. This subgroup also has a significantly higher risk of SBP (2.8% vs 0.2%, p <0.001).
Conclusions:
This is a large retrospective study analyzing the impact of cirrhosis on liver metastasis in patients with colorectal cancer. Patients with concomitant cirrhosis consistently have increased liver metastasis and worse outcomes. The results of this study imply that diligent CRC screening is of utmost importance in patients with cirrhosis. Patients with CRC and coexisting cirrhosis would benefit from routine surveillance such as carcinoembryonic antigen (CEA) screening or CT scans to allow early detection of liver metastases which could potentially improve outcomes.

Colorectal Cancer Patients

No Cirrhosis
(N=250,229)

Cirrhosis
(N=5,370)

p-value

Age (in years)
65.79 ± 13.8
65.04 ± 10.9
<.001

Sex (Female)
47.3%
36.8%
<.001

Charlson Comorbidity Index
8.1 ± 3.6
10.5 ± 3.7
<.001

Mortality
4.2%
8.5%
<.001

Length of Stay
6.6 ± 7.2
7.4 ± 7.2
<.001

Liver Metastasis
23.4%
26.5%
<.001

Hepatic Encephalopathy
0.0%
0.2%
<.001

Portal hypertension
0.3%
26.1%
<.001

Spontaneous Bacterial Peritonitis (SBP)
0.2%
2.8%
<.001
Systematic literature review (SLR) of prognostic factors (PFs) in locally advanced rectal cancer (LARC) and mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer (RC).
Authors: Capdevila Jaume , O’Donnell Sean , Borkowska Katarzyna , Frampton James , Betts Marissa , Maierhofer Courtney , Kalilani Linda , Garside Jamie , Wang Huifen
Published: January 2025

303

Background:
Innovative immunotherapies arebeing developed to improve clinical outcomes in patients (pts) withdMMR/MSI-H LARC who respond poorly to the current standard of care. A comprehensive overview of PFs in dMMR/MSI-H LARC may provide insight into the natural history of this disease to inform clinical study design and pt risk stratification.
Methods:
Systematic searches of bibliographic databases (EMBASE, MEDLINE, Cochrane; 2013–2023) and congress websites (2021–2023) were conducted to identify PFs for tumor response and survival outcomes in adult pts with LARC (SLR1) and dMMR/MSI-H RC (SLR2). Given the expected high volume of evidence, SLR1 was limited to large observational studies (≥1000 pts) and clinical trials (≥100 pts); SLR2 had no such limits.
Results:
95 of 2307 publications met the inclusion criteria for SLR1. Of the PFs reported in ≥20 studies, older age, more lymph node involvement or fewer nodes assessed, higher T-stage or larger tumor size, higher histologic grade, and more comorbidities were most frequently significantly associated with poorer patient prognosis (Table). 3 of 289 publications met the inclusion criteria for SLR2. Neoadjuvant chemoradiation therapy (CRT) compared to chemotherapy (CT) was associated with statistically significant worse disease-free survival (DFS) and distant metastasis-free survival (DMFS), while T- or N-stage, age, and sex did not significantly impact these outcomes. Low vs middle tumor localization was also associated with worse DMFS. Stage III and IV disease were associated with worse RC-specific survival, while surgical procedure (segmental vs extended) showed no difference in overall survival (OS). The addition of neoadjuvant CRT or adjuvant CRT/CT to surgery alone had no impact on OS but was associated with worse DFS.
Conclusions:
Evidence regarding PFs in dMMR/MSI-H RC is scarce and may limit its interpretability, highlighting the need for further research that may be informed by the PFs identified from SLR1. The results from these SLRs may be helpful for optimizing patient management and treatment decision making, and to further contextualize RC clinical trials.

PFs reported in ≥20 studies with ≥75% of studies reporting significant results in pts with LARC.

PF
Studies reporting PF (n)
Studies reporting significant* impact of PF on prognosis (%)
Poorer prognosis group
Top 2 most frequently reported outcomes

Age
59
81.4
Older
OS, DFS

Lymph node involvement/assessment
55
78.2
Yes or higher N stage
OS, DFS

T-stage or tumor size
53
79.2
Higher or larger
OS, DFS

Histologic grade
37
75.7
Higher
OS, pathological complete response (pCR)

Comorbidities
23
87.0
More
OS, pCR

*p-value <0.05 was considered significant as reported in the identified studies.
Disparities and barriers in germline testing among patients with early-onset gastrointestinal cancers.
Authors: Dosunmu Gideon T , Feldt Susan , Pathuri Manish , Gao Guimin , Setia Namrata , Shergill Ardaman
Published: January 2025

35

Background:
Early-onset gastrointestinal cancers (EOGIC) are strongly associated with hereditary predisposition, making germline testing essential for treatment and familial risk management. Disparities in germline testing persist. This study investigates disparities and barriers to germline testing in EOGIC.
Methods:
This IRB-approved retrospective analysis included 864 patients aged 18-49 with GI cancers at the University of Chicago (2018-2023). Data collected included race, gender, age, insurance, family cancer history, and subtype. Outcomes were physician referrals for germline testing and completion. Chi-square tests and logistic regression models assessed predictors of recommendations and completion.
Results:
Of 864 patients, 473 (54.7%) received germline testing recommendations, and 323 (37.4%) completed testing. Completion rates: 30.2% for no insurance, 29.1% for Medicare/Medicaid, and 40.3% for private insurance (p=0.032). Patients with family history of cancer were more likely to be recommended for testing (62.9% vs. 39.5%, p<0.001) and complete it (44.0% vs. 23.7%, p<0.001). In our cohort, no significant racial disparities were observed (p=0.712 and p=0.358). Females were more likely to receive recommendations (59.1%) and complete testing (41.2%) than males (50.9% referral, 34.0% completion, p=0.016 and p=0.029). Patients under 30 had the highest rates of testing recommendation (66.1%) and completion (46.4%), followed by 30-39 (61.7%, 44.4%) and 40-49 (51.2%, 34.0%), p=0.006 and p=0.009. By cancer subtype, colorectal cancer (CRC) patients had the highest referral (66.1%) and completion (45.9%) rates, while anal cancer had the lowest (13.2% referral, 5.3% completion, OR 0.08, p<0.0001). Gastric cancer (52.3% referral, 29.2% completion, OR 0.49, p=0.005) and esophageal cancer (36.9% referral, 20.0% completion, OR 0.31, p<0.0001) also had lower testing rates. Liver cancer (35.4% referral, 27.1% completion, OR 0.38, p<0.0001) and cholangiocarcinoma (45.5% referral, 22.7% completion, OR 0.28, p=0.016) showed similarly low rates.
Conclusions:
Disparities in germline testing were seen among uninsured patients, males, and those with public insurance. CRC had the highest testing rates, while anal, esophageal, liver, and cholangiocarcinoma had lower rates, likely due to lower suspicion of hereditary predisposition. Targeted interventions are needed to improve testing uptake and completion, especially among uninsured and underrepresented populations.
Disparities in organ preservation rate for high-risk stage I rectal cancer.
Authors: Butare Annmarie , Honaker Michael
Published: January 2025

37

Background:
Guidelines for the treatment of high-risk stage I rectal cancer is a curative oncologic resection, while recommendations for stage II/III rectal cancer include neoadjuvant therapy with the option for organ preservation. The paradoxical nature of treating less advanced stage cancer with more morbid surgery calls into question the use of organ preservation strategies (OP) for less advanced disease. While sphincter preservation is appealing, benefits from OP require commitment to preoperative therapy, which may require more significant time and financial commitments than a single-stage curative treatment. This study aims to evaluate disparities in social determinants of health regarding receipt of OP compared to major oncologic resection for high-risk stage I rectal cancer.
Methods:
The National Cancer Database was queried to analyze all patients with high-risk stage 1 rectal cancer between 2004-2021. High-risk stage 1 disease was defined as either T2 or T1 tumors with lymphovascular invasion, or grade 3 or 4 differentiation. Covariates in patients who underwent OP, defined as chemoradiation therapy without oncologic resection or local excision, were compared to those who underwent major oncologic resection. Additional variables included age, sex, race, great circle distance, insurance status, education, facility type, income, rurality, and comorbidity index. Univariate and multivariate analyses were utilized to compare association of covariates to OP.
Results:
Of the 63,762 patients included, 9,261 (14.5%) underwent OP. Increased rates of OP were seen with increasing age (OR 1.029, p<0.0001), female sex (OR 1.147, p<0.0001), higher education level (OR 1.179, p=0.0034), rurality (OR 1.273, p=0.0003) and lower income (OR 0.757 for income >74K, p <0.0001). Interestingly, OP was more frequently utilized at community cancer centers in comparison to comprehensive cancer centers (OR 0.78, p<0.0001) and academic centers (OR 0.842, p=0.0021). Race, insurance status, distance to treatment, and comorbidity index were not statistically significant predictors of OP. Of note, those who underwent OP had a considerable delay in time to first treatment, with median time to treatment of 36 days in comparison to 13 days for oncologic resection.
Conclusions:
Socioeconomic and demographic variables are associated with receipt of OP. While plausible that a treatment strategy that requires frequent office visits, travel expenses, and time off from work may preclude OP, lower income and rurality had increased odds of OP. Future aims should be directed to identifying root causes of disparities in treatment and their clinical consequences.
Colorectal cancer care disparities in an urban diverse population: A tale of two hospitals in the nation’s capital.
Authors: Marshall John , Tesfaye Anteneh A. , Shimberg Connor , Perelgut Chelsea , Zhu Jialing , Dash Chiranjeev
Published: January 2025

38

Background:
Colorectal cancer (CRC) disparities by race and ethnicity are well-documented nationally. In the District of Columbia (DC), Black Americans have an 18% higher incidence and 46% higher mortality rate compared to overall rates among all races/ethnicities. These disparities often stem from long-standing inequities in the social determinants of health, which affect access to cancer prevention, early detection, and treatment. MedStar Georgetown serves a large, urban, diverse population at 2 hospitals: the MedStar Georgetown University Hospital (MGUH) and the MedStar Washington Hospital Center (MWHC). MWHC serves a higher proportion of minoritized patients (pts) with multiple social determinant barriers to care, including those without private health insurance. We hypothesized that disparities would be found in CRC pt care and outcomes when comparing MWHC with MGUH.
Methods:
We conducted a retrospective study of all CRC pts treated during the 2021-2023 period at MGUH and MWHC using the COTA real-world database. Pt demographics, insurance status, and selected clinical data, including but not limited to treatment site, disease stage, tumor molecular testing, and pt survival, were abstracted for analysis. Descriptive, bivariate, and multivariate analyses focused on gender, race/ethnicity, insurance status, receipt of tumor testing, and the interval between diagnosis and therapy initiation and explored survival by these factors in addition to the site of care (MGUH versus MWHC).
Results:
Of the 379 CRC pts receiving care at the Lombardi Comprehensive Cancer Center during the study period, 53% were treated at MGUH and 47% at MWHC. CRC pts at MWHC were more likely than CRC pts at MGUH to be Black Americans (65% vs. 28%, p<0.001) and have 3 or more comorbidities (16% vs. 8%, p=0.22) but were less likely to have early onset CRC (p<0.01) and be on private insurance (36% vs. 23%, p=0.01). Pts treated at advanced stages (stages 3-4) were similar between the two hospitals (64%). In spite of these differences, we did not find any differences between MWHC and MGUH in molecular tumor testing (83% vs. 86%, p=0.41), median time (days) to treatment initiation (28 vs. 26 days, p=0.18), or short-term survival (90% vs. 91%, p=0.95). In analyses comparing care/treatment-related factors with race/ethnicity and insurance status across the 2 hospitals, we did not find any statistically significant differences.
Conclusions:
Contrary to our expectations of finding significant cancer care disparities, we did not observe any differences in molecular tumor testing rates, time to initiation of therapy, or short-term survival by treatment site or race/ethnicity status. Our results suggest that integrated, specialized, guideline-concordant care in comprehensive cancer centers has the potential to eliminate CRC outcome disparities among pts diagnosed at these centers.
Association between visceral adipose tissue radiodensity and overall survival among older adults with colorectal carcinoma.
Authors: Doshi Apoorva , Saad Omar , Martin Landon , Williams Grant Richard , Giri Smith
Published: January 2025

43

Background:
Central obesity is a known risk factor for colorectal carcinoma (CRC); however, the association between visceral adipose tissue (VAT) and survival outcomes remains unclear. This study aims to investigate the relationship between VAT and overall survival (OS) among older adults with CRC.
Methods:
We analyzed data from the Cancer and Aging Resilience Evaluation registry, including adults aged ≥ 60 years with newly diagnosed CRC who were seen at the University of Alabama at Birmingham for initial consultation between October 2017 and April 2024. Using single-slice computed tomography staging scans, we calculated visceral adipose tissue radiodensity (VATD; in Hounsfield units, HU) at the third lumbar vertebra (L3) using validated methods. A lower VATD (more negative score) indicates higher visceral adipose tissue. Participants were followed until death or the study cutoff date of July 10, 2024. Kaplan-Meier survival analysis was performed to estimate OS for those with low VAT (VATD ≥ median VATD) versus high VAT (VATD < median VATD). Additionally, Cox proportional hazards models were utilized to evaluate the association between VATD and OS, adjusting for age at diagnosis, sex, race/ethnicity, skeletal muscle index (SMI), skeletal muscle density (SMD), and cancer stage.
Results:
A total of 190 patients were included, with a median age at diagnosis of 68 years (IQR: 64-75), 56% male, 72% non-Hispanic White, and 40% diagnosed with Stage IV disease. The median SMI and SMD were 42.06 (IQR: 33.81 - 49.52) cm
2
/m
2
and 38.68 HU (IQR: 31.38 - 44.89) respectively. The median VATD was -86.14 HU (IQR: -93.78 – -76.39). Over a median follow-up of 60 months, 96 patients (51%) died. Median OS was 27 months for patients with low VAT and 62 months for those with high VAT (log-rank test, p < .001). After adjusting for confounders, VATD remained independently associated with OS (adjusted Hazard Ratio: 1.41 per IQR decrease; 95% CI: 1.06 – 1.86; p ≤ .05), indicating that each IQR decrease in VATD scores (implying an increase in VAT) is associated with a 41% increased risk of all-cause mortality.
Conclusions:
Our findings demonstrate that increased visceral adipose tissue, indicated by more negative VATD scores, is significantly associated with poorer survival outcomes among older adults with CRC. These results underscore the importance of dietary and weight loss interventions to improve outcomes in this population.
Robot-assisted esophagectomy with extended mediastinal lymph node dissection: The learning curve and surgical outcomes.
Authors: Kawakubo Hirofumi , Takeuchi Masashi , Matsuda Satoru , Kitagawa Yuko
Published: January 2025

457

Background:
We have performed thoracoscopic surgery (TMIE) and robot-assisted surgery (RAMIE) for esophageal cancer with extensive mediastinal lymph node dissection, including resection of the sympathetic nerve layers and the thoracic duct. We studied the learning curve, short-term results, and mid-to-long-term outcomes of RAMIE for esophageal cancer at our institution.
Methods:
We compared surgical times at different stages of the procedure. For mid to long-term outcomes, we analyzed 360 cases of TMIE/RAMIE performed between January 2009 and June 2022, comparing the incidence of postoperative complications, recurrence-free survival, and patterns of recurrence between RAMIE and TMIE. Recurrent laryngeal nerve palsy (C-D I) was evaluated using postoperative endoscopy or contrast swallowing tests to assess even mild paralysis.
Results:
The average console time in the thoracic procedure was 234.4 minutes, with Group A (294.5 minutes, range: 211-397 minutes) showing significantly longer times compared to Group B (190.5 minutes, range: 130-257 minutes). Blood loss was almost 0ml in 10 cases (50%) in Group A and 25 cases (62.5%) in Group B. Postoperative complications included pneumonia in 5 cases (8.3%) and recurrent laryngeal nerve palsy (C-D III) in 5 cases (8.3%), with no significant difference between the groups. However, surgical time for lymph node dissection around the recurrent laryngeal nerve was significantly shorter in Group B compared to Group A. Long-term analysis included 326 TMIE and 34 RAMIE cases. Mild recurrent laryngeal nerve palsy (>C-D I) was observed in 92 cases (28%) of TMIE and 7 cases (21%) of RAMIE, showing a lower tendency in the RAMIE group (p=0.338). Pneumonia (>C-D II) occurred in 57 cases (18%) in the TMIE group and 3 cases (9%) in the RAMIE group, with a relatively lower incidence in the RAMIE group (p=0.178). For patients with cT1N0M0 who did not receive preoperative chemotherapy, the 3-year recurrence-free survival rates were 95% for TMIE and 93% for RAMIE.
Conclusions:
RAMIE demonstrated a significant reduction in operative time due to the standardization of the procedure, particularly in the dissection of recurrent laryngeal nerve lymph nodes and other upper mediastinal maneuvers. RAMIE also showed a potential reduction in the incidence of recurrent laryngeal nerve palsy and pneumonia compared to TMIE. In terms of long-term outcomes, RAMIE maintained local control similar to TMIE, with further improvements in safety expected.
Surgical treatment results for oligo-recurrence of gastric cancer.
Authors: Jang Youjin JIN
Published: January 2025

462

Background:
Despite advancements in diverse treatments, approximately 40-50% of advance gastric cancer patients experience recurrence even after curative resection surgery. The condition where there is a limited recurrence after the control of the primary tumor site is referred to as oligo-recurrence. However, there is scarce reporting on oligo-recurrence after gastric cancer surgery. This study compiled cases of patients who underwent surgery for recurrent gastric cancer after R0 surgery. Since there are no specific treatment guidelines for recurrence after gastric cancer surgery, this research could be beneficial in providing insights and assistance.
Methods:
This retrospective study includes data from 25 patients who underwent surgery for suspected oligo-recurrence of gastric cancer among those who had undergone surgery from June 2008 to May 2018. If a solitary mass suspected of recurrence is identified during surveillance, a PET-CT is performed. Patients with suspicion of peritoneal dissemination, carefully excluded through a multidisciplinary approach, are selectively omitted. All patients undergo excision surgery for both treatment and tissue examination purposes.
Results:
Out of 25 cases, there were 6 cases of paraaortic lymph node enlargement, 9 cases liver nodules, 8 case lung nodules, and 1 case tumor bed mass. In the postoperative tissue analysis, 4 cases of paraaortic lymph node enlargement, 5 cases of the liver nodules, and 1case tumor bed mass were confirmed to be recurrences of gastric cancer. All of lung nodule were diagnosed with lung cancer. All 10 cases underwent chemotherapy after metastatectomy. Among them, 3 cases experienced recurrence and died an average of 12.3 months after surgery. Seven cases did not experience recurrence and have survived with an average survival time of 102 months to date.
Conclusions:
The metastatectomy is safe and effective for patients with oligo-recurrence from GC and can improve their prognosis. For an accurate diagnosis, oligometastectomy is essential. However, our results need to be confirmed by more randomized controlled clinical studies.

Treatment result after metastatectomy.

Case
Diagnosis
Chemotherapy aftermetastatectomy
Recurence after metastatectomy
DFS after metastatectomy
OS after metastatectomy
OS after gastrectomy
Status

1
LN metastasis 1/1
15cycles FOLFOX

147
147
156.4
ALIVE

2
LN metastasis 1/1
37cycles TAS-118
liver metastasis
22
40.6
74.9
DEATH

3
LN metastasis 1/3
12cycles FOLFOX

98.1
98.1
125.5
ALIVE

4
LN metastasis 1/1
35cycles FOLFOX

50.9
50.9
71.3
ALIVE

5
Liver metastasis
ONO tiral
Liver, bone mets.
3.73
27.9
64.6
DEATH

6
Liver metastasis
12cycles FOLFOX

68.3
68.3
122.2
ALIVE

7
Liver metastasis
12cycles FOLFOX

96
96
105.8
ALIVE

8
Liver metastasis
82cycles FOLFOX

55
55
77.4
ALIVE

9
Liver metastasis
12cycles FOLFOX

94.4
94.4
103.9
ALIVE

10
Tumor bed
12cycles FOLFOX
　
9
25.5
24.4
DEATH
Landscape of metastatic colorectal cancer (CRC) using comprehensive circulating tumor DNA (ctDNA) next-generation sequencing (NGS) in India: Expanding beyond RAS and RAF.
Authors: Lavingia Viraj Kiran , Rauthan Amit , Rohatgi Nitesh , Bahl Ankur , Dhar Aparna , Sharma Atul , Chugh Bhuvan , Rajendranath Rejiv , Patil Shekar , Mohapatra Prabrajya Narayan , Bharat Rohit , Sandhir Nippun , Joshi Nisarg , Ostwal Vikas S.
Published: January 2025

49

Background:
Traditional testing in mCRC primarily focuses on RAS and RAF mutations. However, a broader range of emerging biomarkers, collectively termed the "Pressing panel" (PP), identifies patients with RAS/RAF wild-type (wt) tumors who may particularly benefit from anti-EGFR therapy. Comprehensive liquid biopsies provide a non-invasive method for identifying traditional and emerging biomarkers. Limited genomic data, including the prevalence of PP alterations (alts), is available for mCRC patients in India tested by ctDNA NGS.
Methods:
We reviewed the results of Guardant360 (Guardant Health, Inc.) ordered for patients with mCRC as part of routine clinical practice in India through July 2024. NGS analyzed plasma samples at a CLIA-certified, CAP-accredited central laboratory. Guardant360 analyzes ctDNA for mutations (mts), insertions and deletions, amplifications (amps), and fusions in up to 83 genes, including PP genes, i.e., KRAS, NRAS, BRAF, ERBB2, PIK3CA, PTEN, AKT1, ALK, ROS1, NTRK, RET, and MSI status. The Indian cohort's prevalence of PP mts was compared to that from other countries in Asia and Middle East (AME). Timing of testing relative to line of therapy was unknown.
Results:
Among 145 samples from India, ctDNA was detected in 92% (n=134). Median age was 59 years, with women comprising 40%. The median turnaround time from blood collection to result was 7 days. The mean mts count per sample was 5, and the median variant allele frequency was 1.5%. Frequent mts were in APC (53%), KRAS (56%), and SMAD4 (13%), while amps of EGFR (16%) and FGFR1 (9%) were common. Clinically relevant fusions were observed in 3% of patients. KRAS, NRAS, and/or BRAF V600E alterations were found in 63% of both India and AME samples. PP alts were identified in 24% and 27% of Indian and AME patients, respectively. Most frequent PP alts included PIK3CA (15%), PTEN (3%), and MET amp (2%). The prevalence of most of the PP alts was similar between the Indian and AME cohorts (Table), with minor differences observed in PIK3CA (15% vs 18%) and MSI-High (3% vs 1%). In patients with RAS/RAF wild-type lacking EGFR-amp, 9.5% (India) and 18% (AME) harbored at least one PP alt.
Conclusions:
This study highlights the role of liquid CGP for characterizing the mutational landscape and identifying PP mts for patients from India with advanced CRC.

Pressing panel alterations.

PP Alteration
INDIA % (n=134)
AME % (n=720)

ERBB2 Amp
1%
2%

MET Amp
2%
3%

ALK Fusion
0%
0%

ROS1 Fusion
0%
0%

NTRK1 Fusion
1%
0%

RET Fusion
0%
1%

ERBB2 Mut
1%
2%

PIK3CA Mut
15%
18%

PTEN Mut
3%
3%

AKT1 Mut
0%
1%

MSI-High
3%
1%
The immunogenomic landscape of primary and metastatic gastroesophageal adenocarcinoma.
Authors: Wang Xin , Chen David , Bach Yvonne , Wilson Gavin W , Aoyama Hiroko , Allison Frances , Sotov Valentin , Tran Christine , Restrepo Michelle , Chen Eric Xueyu , Ma Lucy Xiaolu , Wakeam Elliot , Yeung Jonathan , Wong Rebecca KS KS , Veit-Haibach Patrick , Kalimuthu Sangeetha , Wang Ben X , Jang Raymond Woo-Jun , Haibe-Kains Benjamin , Elimova Elena
Published: January 2025

493

Background:
Metastatic gastroesophageal adenocarcinoma (GEA) is a heterogeneous disease with an overall poor prognosis. The tumour microenvironment (TME) between the primary and metastatic compartment is not well characterized. This study aims to describe the immunogenomic features of matched primary and metastatic GEA and their correlation with clinical outcomes.
Methods:
We performed whole exome sequencing (WES, n=36) and total RNA sequencing (RNA-seq, n=36) on a prospectively collected cohort of metastatic GEA, of which 14 had matched primary and metastatic tissues. We used TME deconvolution (Bagaev et al., 2021) comparing between the primary and metastatic compartments. Using an orthogonal technology, we further integrated immune checkpoint-directed multiplex immunohistochemistry (mIHC) for 22 patients with matched primary and metastatic samples.
Results:
The median age of our cohort was 61 (range 27-89), primarily male (n=28, 77%), and non-Asian (n=32, 89%). All had metastatic GEA at time of diagnosis. Differential expression showed activation of immune pathways such as tumor necrosis factor signalling and interferon-gamma response in the metastatic compartment. Deconvolution of the TME demonstrated 29% of primary tissues having an immune-inflamed TME compared to 61% of metastatic tissues (p=0.032). Exploring immune cell types, metastatic compartment is characterized by higher abundance of naïve and mature B cell populations (p<0.001), while primary compartment is enriched with CD4+ T cells (p<0.01). In matched cases, only 2 of 14 (14%) had concordant TME subtypes between primary and metastatic samples suggesting high degree of immune divergence. Furthermore, expression of common immune checkpoints aligned more with TME subtypes than within patient compartments suggesting common pathways of immune evasion. M-IHC showed both T-cell and immune checkpoint markers are enriched at the tumor margins compared to the tumor center in both primary and metastatic compartments (CD4; p<0.0001, CD8; p<0.001, CD68; p<0.001). There was a significant increase in the number of CD68+/CD163+/PDL1+ M2-like macrophages in the tumor margins (p<0.0001). Consistent with our deconvolution analysis, there are higher CD4+ T cells in the matched primary compared to metastatic samples. Long-term survivors (>16 months) had decreased number of CD68+ macrophages in the tumor center (p=0.019).
Conclusions:
Primary and metastatic GEA have divergent TME. This may partially explain varying responses to chemo-immunotherapy approaches. Therapies aimed at modifying TME may provide personalized treatment options.
Surrogacy between pathological complete response and overall survival: An individual patient data analysis of eight RCTs on neoadjuvant treatment plus surgery for esophageal cancer.
Authors: Okui Jun , Nagashima Kengo , Matsuda Satoru , Sato Yasunori , Kawakubo Hirofumi , Ruhstaller Thomas , Thuss-Patience Peter C. , Aparicio Thomas , Piessen Guillaume , van der Zijden Charlène J. , Mostert Bianca , Wijnhoven Bas P.L. , Tsushima Takahiro , Takeuchi Hiroya , Kato Ken , Kitagawa Yuko
Published: January 2025

498

Background:
Overall survival (OS) is the gold standard endpoint of treatment efficacy but requires an extended follow-up period. This study aimed to determine the validity of pathological complete response (pCR) as a surrogate endpoint for OS.
Methods:
The individual-level surrogacy between categorical outcome and OS was assessed using Kendall correlation coefficient, τ. Because no method has been reported to estimate τ between categorical variables and OS, we proposed the new method using an inverse probability of censoring weighting (IPCW) estimator adjusted for tied data that occur when applied to categorical outcomes. To evaluate the validity of this new method, we conducted simulations to compare its estimation accuracy with existing methods. A systematic review for all phase III RCTs comparing therapies in perioperative settings for resectable advanced esophageal and gastroesophageal junction cancer was performed and individual patient data (IPD) were requested from all included trials. Finally, surrogacy between pCR and OS was assessed using our proposed method.
Results:
Across all scenarios with varying τ values, sample sizes, and censoring proportions, the proposed method showed the lowest bias compared to the existing statistical methods. In total, 23 eligible trials were identified and IPD were available from eight RCTs (JCOG1109, JCOG9907, JCOG9204, FFCD9901, FFCD9102, SAKK75/08, CROSS, and KOK), including 1688 patients who received neoadjuvant therapy. For trial-level analysis, pCR showed a strong correlation with a determination of correlation of 0.65 when limited to neoadjuvant chemotherapy (NAC) trials. For individual-level analysis, in patients who received NAC, the hazard ratio (HR) for OS of pCR was 0.25 (95% CI: 0.13 - 0.47), and τ between OS and pCR was 0.225. While in patients who received neoadjuvant chemoradiotherapy (NACRT), the HR was 0.54 (95% CI: 0.45 - 0.66), and τ was 0.189. Additionally, τ between OS and pathological grade (pGrade), OS and tumor regression grade (TRG) was 0.196 and 0.143, respectively. As a reference, hypothetical data showed that in order to achieve a τ of 0.8 between pCR and OS, it is necessary to be able to clearly identify the prognosis to the extent that an HR of 0.09 (95% CI: 0.08 - 0.11) can be obtained.
Conclusions:
While pCR is sensitive enough to stratify prognosis and exhibit strong trial-level surrogacy, no individual-level surrogacy was demonstrated, making them insufficient to replace OS. It should be noted that there are substantial differences in prognostic stratification and potential use of pCR as primary endpoints in clinical trials.
The impact of protein-energy malnutrition on clinical outcomes in hospitalized gastric cancer patients: A population-based analysis.
Authors: Iqbal Rabia , Kimball Henry , Gaddam Mrunanjali , Peshin Supriya , Sinha Samridhi , Quadri Kalimullah
Published: January 2025

503

Background:
Protein-energy malnutrition (PEM) is considered an adverse prognostic factor in various clinical conditions. Patients with gastric cancer are at an increased risk of malnutrition because of factors such as loss of appetite due to the tumor, difficulty swallowing, malabsorption, and metabolic changes caused by the cancer. However, the implications of protein-energy malnutrition (PEM) in gastric cancer patients are not well studied. Through this study, we wanted to examine how PEM affects clinical outcomes in hospitalized patients with gastric cancer.
Methods:
We used the National Inpatient Sample (NIS) from 2018 to 2020 to detect patients with a primary diagnosis of gastric cancer and a secondary diagnosis of protein energy malnutrition (PEM). We used the chi-square and student T-test to analyze categorical and continuous variables. Confounders were adjusted using multivariable regression analysis, and the adjusted odds ratio (aOR) was calculated.
Results:
We detected a total of 1673915 patients with the primary diagnosis of gastric cancer using ICD-10 codes. Of them, 401,739 (24%) of the patients had a secondary diagnosis of PEM. The mean age of the patients was 66 years (p-value <0.01). Of these, 56% of the patients were male, while the remaining 44% were female (p-value <0.001). Based on race, 68% of the patients belonged to the White Race, 12% were African Americans, and 11% were Hispanics (p-value <0.001). It was observed that the presence of PEM was associated with higher mortality (aOR 1.6, p-value <0.001). There was also higher hospitalization cost ($109522 vs. 75725, p-value <0.001) and mean length of stay (LOS) (9.1 days vs. 5.6 days, p-value <0.001). PEM in gastric cancer patients was also associated with higher odds of sepsis (aOR 1.6, p-value <0.001), gastritis (aOR aOR 1.2, p-value <0.001), gastrointestinal (GI) bleeding (aOR 1.1, p-value <0.001) and acute kidney injury (AKI) (aOR 1.7, p-value <0.001).
Conclusions:
Our study demonstrates that protein-energy malnutrition (PEM) is associated with increased mortality, higher hospitalization costs, and longer stays in hospitalized gastric cancer patients. These findings emphasize the need for regular nutritional assessment and management to improve clinical outcomes in this population.

Comparison of outcomes in hospitalized gastric cancer patients with and without protein-energy malnutrition (PEM).

Hospital Outcomes
Gastric Cancer Patients with PEM
Gastric Cancer Patients without PEM
Adjusted Odds ratio (aOR)
95% Confidence Interval
P-value

Mortality
9.1% (n=36999)
5.3% (n=68100)
1.6
1.5-1.7
<0.001

Length of Stay
9.1
5.6
3.0
2.7-3.3
<0.001

Sepsis
10% (n=41915)
6.4% (n= 82035)
1.6
1.5-1.6
<0.001

Gastritis
3.9% (n=16174)
3.3% (n=41879)
1.2
1.1-1.31
<0.001

GI Bleeding
7.1% (n= 28949)
6% (n= 28949)
1.1
1.0-1.2
<0.001

AKI
28% (n=117439)
19% (n=1268134)
1.7
1.7-1.8
<0.001