bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative restricted mean survival time (RMST) analysis of survival in advanced hepatocellular carcinoma (aHCC) from pivotal phase III trials: IMbrave-150, ORIENT-32, CARES-310, HIMALAYA, and CM-9DW.
Authors: Pazo Cid Roberto A. , Blanco Abad Carmen , Gomila Pons Paula , Comin Orce Ana , Gascon Ruiz Marta , Campos Ramírez Sara Elena , Gomez Pablo , Alvarez Alejandro Maria , Torres Irene , Sarría Luis , Larrosa Raquel , Serrablo Alejandro , Fuentes Olmo Javier
Published: January 2025

597

Background:
In advanced hepatocellular carcinoma (aHCC), the evaluation of overall survival (OS) and progression-free survival (PFS) through restricted mean survival time (RMST) provides a nuanced understanding of treatment efficacy. The RMST analysis serves as a valuable complement to the hazard ratio (HR) analysis, offering insights into the average survival time over a specified period. This study compares RMST analyses of OS at 24 and 36 months, and PFS at 12 and 18 months, across five pivotal phase III trials: IMbrave-150, ORIENT-32, CARES-310, HIMALAYA, and CM-9DW.
Methods:
Data from the experimental arms of the five phase III trials were analyzed. The RMST was calculated using the area under the Kaplan-Meier survival curves up to the specified time points. Specifically, OS was evaluated at 24 and 36 months, and PFS at 12 and 18 months. The RMST provides an estimate of the average time that patients survive (for OS) or remain progression-free (for PFS) within a specific timeframe. Kaplan-Meier survival curves were digitized if not available in raw form, and the area under the curve (AUC) was computed using numerical integration methods. RMST values were extracted from the AUC for the specified periods. This approach accounts for censored data and provides a robust comparison of survival times across different treatment groups.
Results:
The results for OS RMST at 24 and 36 months and PFS RMST at 12 and 18 months are summarized in the table.
Conclusions:
Angiogenesis inhibitor + immune checkpoint inhibitor combinations (Atezolizumab + Bevacizumab; Sintilimab + IBI305) provide the most favorable RMST outcomes in terms of OS and PFS.

Restricted mean survival time (RMST) comparison of OS and PFS (months).

aHCC 1L Phase III Trials
Treatment Arm
OS 24m
OS 36m
PFS 12m
PFS 18m

IMbrave-150
1, 2

Atezolizumab + Bevacizumab
17.50
22.79
9.69
13.29

ORIENT-32
3

Sinitilimab + IBI305
17.01
21.09
9.18
12.54

CARES-310
4

Camrelizumab + Rivoracenib
16.34
19.75
9.29
12.14

HIMALAYA
5, 6

Tremelimumab + Durvalumab
15.36
18.76
8.95
12.02

CM-9DW
7, 8

Nivolumab + Ipilimumab
15.87
20.08
8.74
11.78

1
Finn et al. N Engl J Med 2020;382:1894-905;
2
Cheng et al. J Hepatol 2022;76:862-873;
3
Ren et al. Lancet Oncol 2021;22:977–90;
4
Qin et al. Lancet 2023;402:1133–46;
5
Abou-Alfa et al. NEJM Evid 2022;1(8):EVIDoa2100070;
6
Sangro et al. Ann Oncol 2024;35:448-457;
7
Galle et al. J Clin Oncol 2024;42(suppl 17):abstr LBA4008;
8
Decaens et al. Ann Oncol 2024;35:S657.
The relationship between the tumor microenvironment of hepatocellular carcinoma and apparent diffusion coefficient.
Authors: Morine Yuji , Saito Yu , Yamada Shinichiro , Teraoku Hiroki , Miyazaki Katsuki , Ikemoto Tetsuya , Shimada Mitsuo
Published: January 2025

616

Background:
The tumor microenvironment is critical for the acquisition of tumor malignancy in various cancer types. The objectives of this study were to investigate whether the levels of cancer-associated fibroblasts (CAFs) and tumor-associated macrophages (TAMs) reflect the prognosis of patients with hepatocellular carcinoma (HCC) after hepatectomy (Hx) and to determine whether the apparent diffusion coefficient (ADC) from diffusion-weighted imaging (DWI) reflects CAF and TAM expression.
Methods:
The study cohort comprised 109 patients who underwent initial curative resection for HCC. Alpha smooth muscle actin (αSMA) was selected as a CAF marker and CD204 as a TAM marker. Protein expression was immunohistochemically evaluated in the intratumoral regions of resected specimens. Clinicopathological factors, including the long-term prognosis after Hx, were investigated between αSMA-negative and -positive tumors and between CD204-negative and -positive tumors. The correlation between CAF/TAM marker expression and the calculated minimum ADC using DWI was also evaluated.
Results:
αSMA-positive expression was correlated with tumor number, invasive growth pattern, and advanced stage. CD204-positive expression was correlated with the presence of venous invasion. Both αSMA-positive expression and CD204-positive expression were significant prognostic factors in the univariate analysis of overall survival and disease-free survival. αSMA/CD204 double positivity was associated with an extremely poor prognosis after Hx and was a significant independent prognostic factor for overall survival (
p
=0.02, hazard ratio: 3.27). Patients with double positivity also showed a significantly higher ADC
low
rate (83%).
Conclusions:
Expression of both CAF and TAM markers reflected a poor prognosis after Hx. Furthermore, the preoperative ADC could be a clinical surrogate marker in the tumor microenvironment in patients with HCC.
Effect of marital status and race on survival of patients with well differentiated neuroendocrine tumors (NETs).
Authors: Stringer Amy D. , Kollu Lekhya , Egleston Brian L. , Vijayvergia Namrata
Published: January 2025

654

Background:
Socioeconomic status factors (SES) such as marital status, income, and race can influence and enhance disparities in cancer incidence and outcomes. Marriage has documented positive impacts on overall survival of numerous cancer types. Consequences of divorce have been less explored. The unique indolent, secretory nature of NETs may be differentially affected by SES factors. This study identifies implications of marital status and sex on 5-year survival rates of different racial groups diagnosed with NETs within the Surveillance, Epidemiology, and End Results (SEER) database between 2000-2020 while controlling broadly for the type of treatment received.
Methods:
Within the SEER data base patients with reported sex, race, marital status and treatment who were diagnosed with well differentiated NETs were selected excluding carcinomas. Relative and disease specific 5-year survival analyses were calculated with 95% confidence intervals and age standardized. Three groupings were analyzed single, separated/divorced/widowed and domestic-partner/married.
Results:
For all races and sexes, relative survival for individuals in a union was higher than those who were single, or separated, divorced/widowed [86.9% (CI 86.1% - 87.7%); 79.3% (77% to 81.3%); and 79.2% (78% to 80.3%) respectively]. When individuals of each marital status group were compared by matching sex and race, there were no significant differences in relative survival. But males of any race who left a union had lower chances of survival than corresponding females [72.4% (69.7% to 74.9%) vs 81.6% (80.3% to 82.8%)]. As expected, all groupings who received surgical treatment had a higher relative survival than those who did not. Those who received surgical treatment while in a partnership had a higher relative survival then those who were separated [94.5% (93.6% to 95.3%) vs 88.7% (87.3% to 89.9%)]. All marital groupings who underwent surgery or did not, had comparable relative survival between races; except, black individuals in a partnership had improved outcomes compared to the white population. More specifically, when accounting for race, sex, marital status and treatment received, black men who did not undergo surgery had a higher relative survival compared to white men [69.9% (62.2% to 76.3%) vs 59.4% (56.6% to 62.1%)]. All the same conclusions were statistically significant for disease specific survival.
Conclusions:
Due to NETs slow growing nature SES factors play a major role in the care of patients living with them. Our findings demonstrate generally, irrespective of race, sex, or surgical treatment, being involved in a union is advantageous, showing a protective effect on patient survival, while parting from a union could be deleterious as it is tied to less favorable outcomes. These findings underscore the importance of considering these factors in treatment and care strategies.
Matching adjusted indirect comparison (MAIC) of
177
Lu-DOTATATE vs. sunitinib as first-line (1L) treatment for advanced grade 2 (G2) pancreatic neuroendocrine tumors (pNETs).
Authors: Srirajaskanthan Raj , Capdevila Jaume , Deshayes Emmanuel , Navalkissoor Shaunak , Folitar Ilya , Lovelle Marcos , Delea Thomas , Gupta Subhajit , Kumar Anup , Pathak Purnima
Published: January 2025

664

Background:
The phase 3 NETTER-2 trial recently demonstrated a statistically significant improvement in progression-free survival (PFS) with [
177
Lu]Lu-DOTA-TATE (
177
Lu-DOTATATE) plus long-acting octreotide (Oct LAR) vs. high-dose Oct LAR in patients with G2/G3 gastroenteropancreatic neuroendocrine tumors in the 1L setting, across tumor grades and origins (including pNETs). However, no head-to-head comparison of
177
Lu-DOTATATE to other treatment options was conducted. Sunitinib is a currently recommended 1L treatment for patients with advanced G2 pNETs. The Raymond 2018 study is the only study that assessed sunitinib in advanced pNETs and provided sub-group data for the 1L setting (80% of the patients had G2 tumors). We aimed to determine the relative efficacy (PFS) of
177
Lu-DOTATATE + Oct LAR vs. sunitinib as 1L treatment for advanced G2 pNETs using MAIC.
Methods:
An unanchored MAIC (due to absence of a common comparator) of PFS in patients with advanced G2 pNETs treated in 1L with
177
Lu-DOTATATE + Oct LAR vs. sunitinib was conducted using individual patient data from NETTER-2 and aggregated data published in the Raymond 2018 study. Baseline characteristics and PFS data for the sunitinib arm were available for the treatment-naïve subgroup and were considered for the analysis. Baseline characteristics considered in the MAIC included age, sex, race, prior somatostatin analogue use, and number as well as location of involved disease sites. Multiple scenarios with various combinations of covariates were considered with multivariate Cox-regression of NETTER-2 used to identify covariates predictive of PFS. Finally, the combination of covariates with a reasonable effective sample size (ESS) was selected.
Results:
The final ESS was estimated to be 22 for
177
Lu-DOTATATE + Oct LAR, representing 43% of the original sample size (n=50), whereas sample size for sunitinib arm was 61 patients. After matching and weighting, patient characteristics were well balanced. MAIC analysis showed a statistically significant PFS benefit with 1L
177
Lu-DOTATATE + Oct LAR vs. sunitinib in G2 pNET (PFS hazard ratio: 0.23 [95% CI: 0.12–0.45]). Unadjusted comparison showed similar results (PFS hazard ratio: 0.34 [95% CI: 0.19–0.61]). Results were consistent across various scenarios assessed.
Conclusions:
Using MAIC to adjust for cross trial differences, PFS comparison favored
177
Lu-DOTATATE + Oct LAR over sunitinib as 1L treatment of patients with G2 pNET.
Assessing socioeconomic disparities and the likelihood of multimodal treatment utilization in patients with pancreatic cancer using SEER Medicare data.
Authors: Nataliansyah M. Muska , Pezzin Liliana E , Xing Yun , Nattinger Ann B. , Evans Douglas B. , Tsai Susan
Published: January 2025

677

Background:
Optimal treatment for pancreatic cancer necessitates multimodal therapies combining surgery, chemotherapy, and radiation. Socioeconomic determinants of health may influence access to these treatments, leading to disparities in outcomes. This study examines the association between socioeconomic status (SES) and the likelihood of receiving multimodal treatment among pancreatic cancer patients using SEER Medicare data.
Methods:
Our study population consists of elderly persons diagnosed with pancreatic cancer from the 2008–2017 SEER-Medicare dataset. A multinomial logistic regression controlling for sociodemographic characteristics, cancer stage, comorbidities, geographic region, and ecological measures of urbanicity and SES was used to assess the likelihood of receiving one of three mutually exclusive treatment categories: no treatment, one modality (surgery, chemotherapy, or radiotherapy), or multiple modalities (different combinations of surgery, chemotherapy, and radiotherapy), with multiple modalities as the reference group. Survival analysis was conducted using Kaplan-Meier curves (KMC) and Cox proportional hazards (CPH) models.
Results:
Adjusted analyses showed that among stages 0–3 patients, living in areas with a high percentage of individuals without a high school education (non-HS) was associated with increased odds of receiving no treatment (OR = 1.26, p < 0.01) and one modality (OR = 1.20, p < 0.01) versus multiple modalities. Low median household income was linked to higher odds of no treatment (OR = 1.30, p < 0.01) and one modality (OR = 1.16, p < 0.05). This pattern persisted in stage 4 patients, where high non-HS percentage increased odds of no treatment (OR = 1.38, p < 0.01), and low median income was associated with higher odds of no treatment (OR = 1.25, p < 0.05). Non-Hispanic Black patients had higher odds of receiving no treatment in both stages 0–3 (OR = 1.26, p < 0.05) and stage 4 (OR = 1.91, p < 0.01) compared to Non-Hispanic Whites. Being married was associated with reduced odds of receiving no treatment for stages 0–3 (OR = 0.53, p < 0.01) and stage 4 (OR = 0.55, p < 0.01). Lower SES and being Non-Hispanic Black are associated with decreased likelihood of receiving multimodal treatment across all stages. Patients receiving multimodal therapies demonstrated improved survival on our KMC analysis, and CPH models indicated lower mortality for those receiving multiple modalities.
Conclusions:
Socioeconomic disparities significantly influence multimodal treatment utilization in pancreatic cancer. Lower SES indicators—high non-HS percentages, low median income—and being Non-Hispanic Black are associated with decreased use of multimodal therapies and poorer survival. Addressing these disparities is essential to ensure equitable access to optimal treatments and improve survival rates.
Disparities in outcomes of pancreatic cancer hospitalizations: A ten-year trend study.
Authors: Olafimihan Ayobami Gbenga , Jackson Inimfon Nsikak , Ugwuja Ferdinand , Nwachukwu Chiamaka Elsie , Mullane Michael Russell
Published: January 2025

683

Background:
Pancreatic cancer is the third leading cause of cancer mortality in the United States with 51,750 estimated deaths from Pancreatic cancer in 2024. Demographic variations have been reported with Pancreatic cancer. Our aim was to identify trends in demographic-specific disparities in inpatient pancreatic cancer outcomes.
Methods:
This is a retrospective longitudinal trends study using the Nationwide Inpatient Sample (NIS) database (2010-2019). We identified hospitalizations with pancreatic cancer using ICD-9 and ICD-10 codes. We highlight disparities in mortality outcomes stratified by age, gender and race.
Results:
There were 992,550 hospitalizations of pancreatic cancer patients between 2010 and 2019. Over the period, the mean age at hospitalization was similar at 68 years (P = 0.006). A majority of the admissions were elderly patients (≥65 years) identifying as males and Caucasians (P < 0.01). Most patients had Medicare and were in large and urban teaching hospitals (P < 0.001). Over the decade, there was an overall decline in inpatient mortality, from 8.2% in 2010 to 7.1% in 2019 (P trend = 0.004). Amidst the age subgroups, only the elderly patient group experienced a significant decline in mortality rate (8.8% to 7.3%; P trend = 0.004). The young adult population (<45 years) had a trend towards increasing mortality rate, but it was not significant (P trend= 0.139). On gender subgroup analysis, only males had a significant decline in mortality rate (P trend= 0.003). On racial subgroup analysis, only Caucasians had a significant decline in mortality trend (P trend= 0.004) during the study period.
Conclusions:
There was an overall improvement in the mortality outcome of pancreatic cancer hospitalizations. On sub-group analysis, significant decline in mortality over the decade were seen only in elderly, male and Caucasian patient groups. Targeted research is needed in understanding the root causes of these disparities in pancreatic cancer outcomes and develop effective intervention to bridge this gap.

Trends in mortality outcomes of pancreatic cancer hospitalizations by demographic subgroups.

Mortality rate, %
2010
2011
2012
2013
2014
2015
2016
2017
2018
2019
P- Trend value

Overall
8.21
7.94
7.85
7.70
7.73
7.68
7.46
7.87
7.47
7.14
0.004

Young (<45 years)
4.45
5.55
5.23
6.08
6.27
5.32
3.63
6.84
6.95
6.35
0.14

Middle-aged (45- 64 years)
7.55
7.24
7.74
7.32
7.03
6.99
7.62
6.80
6.74
6.91
0.06

Elderly (>65 years)
8.81
8.44
8.04
8.00
8.22
8.19
7.54
8.48
7.87
7.29
0.004

Females
7.72
7.32
7.23
7.15
6.99
7.31
6.72
7.38
7.01
6.87
0.08

Males
8.67
8.57
8.44
8.22
8.44
8.04
8.13
8.32
7.90
7.38
0.003

Whites
7.94
7.49
7.48
7.39
7.81
7.29
6.81
7.39
7.19
6.80
0.004

Blacks
9.87
9.40
9.38
9.15
8.35
8.13
9.40
9.01
8.55
8.41
0.07

Hispanics
7.10
8.99
8.02
6.85
6.66
8.80
7.54
7.43
7.10
6.14
0.05
Changes in peri-operative chemotherapy and radiation use among patients with resected pancreatic ductal adenocarcinoma (PDAC) between 2004-2021 in the US SEER dataset.
Authors: Su Alan , Rocha Flavio G. , Lopez Charles D. , Yun Jin , Kennecke Hagen Fritz
Published: January 2025

697

Background:
PDAC peri-operative management changed over 20 years. Randomized data supports adjuvant and multiagent chemotherapy (CT), while peri-operative chemoradiotherapy (RT) was used selectively in the US. We examined recent trends in treatment with outcomes in surgically resected PDAC patients.
Methods:
Using the Surveillance, Epidemiology, and End Results (SEER) 17 dataset, we identified surgically resected primary M0/MX PDAC cases from 2004-2021 over 3-year periods (P1-P6). Neoadjuvant (NCT), adjuvant (ACT), or multiagent (MACT) CT scheduling was included. χ² analysis assessed cohort characteristics over time and multinomial logistic regression assessed odds of CT allocation adjusted by cohort characteristics. Multivariable Cox proportional hazards model assessed treatment-related overall survival (OS) adjusted for cohort characteristics.
Results:
Among 55,293 cases of M0/MX PDAC, 21,904 (40%) completed surgery. Median age was 66 years; stages were T1/T2/T3/T4 (8.0/25/59/6.0%) and N0/N+ (38/54%). RT use declined (P1:P6, 41%->18% p<0.001) while CT use increased (P2:P6, 63%->79%, p<0.001). NACT (P2:P6, 4.1%->23% p<0.001) and MACT (P2:P6, 1.6%->20%, p<0.001) use increased while ACT decreased (P2:P6, 58%->36%, p<0.001). CT is likely to be allocated to young patients (<65yo) with Stage II-III tumors located at the pancreatic head (OR>1.00, p<0.001). Median OS increased over time (P1:P6, 18mo->32mo, p<0.001). Multivariable analysis shows that Adjuvant RT (HR 0.84 [0.81-0.87], p<0.001) and all CT (NCT: HR 0.71 [0.66-0.77], p<0.001; ACT: HR 0.63 [0.60-0.66], p<0.001; MACT: HR 0.65 [0.60-0.71], p<0.001) improved OS.
Conclusions:
This study shows decreased RT and increased CT adoption from 2004-2021. Median OS improved over the years, potentially due to peri-operative advances during this study period.

Trends in treatment use over 3-year periods.

RTN (%)
CTN (%)
Neo CTN (%)
MACTN(%)

P1: 2004-2006N=2661
1087 (41)

0 (0)
a

0 (0)
a

0 (0)
a

P2: 2007-2009N=3185
1185 (37)
2021 (63)
129 (4.1)
50 (1.6)

P3: 2010-2012N=3536
1226 (35)
2460 (70)
267 (7.6)
138 (3.9)

P4: 2013-2015N=3947
1210 (31)
2880 (73)
434 (11)
244 (6.2)

P5: 2016-2018N=4224
971 (23)
3256 (77)
676 (16)
491 (12)

P6: 2019-2021N=4351
787 (18)
3430 (79)
1003 (23)
857 (20)

a
No cohorts reported chemotherapy use during period 1.

RT: Radiation Therapy; CT: Chemotherapy; NCT: Neoadjuvant Chemotherapy; MACT: Multiagent Chemotherapy.
A single institution retrospective study evaluating mitomycin dosing during chemoradiation in anal squamous cell carcinoma.
Authors: Gong Jenny , Simon Emily , Selfridge J. Eva , Bajor David L. , Steinhagen Emily , Lumish Melissa Amy , Chakrabarti Sakti , Mohamed AMR , Henke Lauren E. , Dorth Jennifer Anne , Mahipal Amit , Conces Madison
Published: January 2025

7

Background:
Mitomycin (MMC) is used concurrently during chemoradiation (CRT) treatment for non-metastatic anal squamous cell carcinoma (SCCA). The most effective dosing of MMC is not established, and due to concerns for tolerability, many have adopted a dose-reduction strategy. This study evaluates differences in treatment response and recurrence between MMC dosing in this setting.
Methods:
Demographics, age, smoking history, staging, and treatment history were collected for patients with non-metastatic SCCA treated with CRT from January 2011-September 2024 at a tertiary cancer center. Chi-square analyses compared categorical variables, and ANOVA tests were used to compare treatment response and recurrence between 3 MMC doses (12mg/m
2
x 1 dose with cap of 20mg, 10mg/m
2
x 2 doses, 10mg/m
2
x 1 dose).
Results:
There were 124 patients, 6 of whom were excluded due to lack of follow up. Of the 118 included, 70% were female, 16% Black, 3% Hispanic/Latino, and 58% current/former smokers. Median age was 61 years (31-98). Thirty-three (28%) pts were treated with MMC 12mg/m
2
, 71 (60%) with 10mg/m
2
x2 doses, and 14 (12%) with 10mg/m
2
x1 dose. Stage I included 18% of 12mg/m2, 7% of 10mg/m
2
x2 doses, and 7% of 10mg/m
2
x1 dose; stage II included 18% of 12mg/m2, 37% of 10mg/m
2
x2 doses, and 50% of 10mg/m
2
x1 dose; stage III included 64% of 12mg/m2, 56% of 10mg/m
2
x2 doses, and 43% of 10mg/m
2
x1 dose. A total of 39.7% were treated with MMC/capecitabine and 60.3% with MMC/fluorouracil. Complete response was achieved in 91% receiving the 12mg/m
2
, 75% receiving 10mg/m
2
x2 dose, and 71% receiving 10mg/m
2
x1 dose (p=0.13, Table 1). Using logistic regression with MMC dose, stage, age, and smoking status as independent predictors, the odds of achieving complete response were lower in 10mg/m
2
x2 doses (p=0.03) and 10mg/m
2
x1 dose (p=0.03) compared to 12mg/m
2
. Local, regional, or metastatic recurrence occurred in 15% of pts receiving 12mg/m
2
, 17% of 10mg/m
2
x2 doses, and 7% of 10mg/m
2
x1 dose. No significant difference was seen in local (p=0.52), regional (p=0.93), metastatic (p=0.87), or overall recurrence (p=0.65) between the MMC doses.
Conclusions:
Odds of achieving complete response was greater with 12mg/m
2
dosing. Local, regional, and metastatic recurrence were similar among the different MMC dosing cohorts. Differences in tolerance and side effects should be delineated to guide individualized dosing of MMC.
MEK inhibitor-based therapy in metastatic pancreatic adenocarcinoma with
KRAS
G12R alteration.
Authors: Auckley Elizabeth , Ying Grace , Yohay Stephanie , Aldakkak Mohammed , Thalji Samih Z , Vakili Parnian , Grahl Justin , Mayer Bradley , Shahjehan Faisal , Low Soon Khai , Evans Douglas B. , Christians Kathleen K. , Seo Yongwoo David , Erickson Beth , Hall William Adrian , McFall Thomas , Kurzrock Razelle , George Ben , Kamgar Mandana
Published: January 2025

725

Background:
Pancreatic ductal adenocarcinoma (PDAC) is largely driven by oncogenic alterations in the
KRAS
,
TP53
,
CDKN2A/B
, and
SMAD4
genes.
KRAS
G12R accounts for nearly 20% of
KRAS
alterations in PDAC, is biologically unique, and offers the potential for improved response to MEK inhibitor (MEK-inh)-based therapy. As part of the MCW-Master-PREDICT (NCT05802069) observational study, we evaluated the efficacy of MEK-inh-based therapy matched to the unique molecular alterations in the tumor of each patient as recommended by the molecular tumor board.
Methods:
From March 2022 to December 2023, 8 patients with metastatic PDAC were treated with MEK-inh-based therapy. Molecular profiling was performed by Tempus (648 genes) in 7 patients, and FoundationOne (324 genes) in 1 patient. Description of molecular alterations, matched therapies, and efficacy of treatment are provided.
Results:
The median age of patients starting MEK inhibitor-based therapy was 69 years, with 62% of them being female. The molecular characteristics and matched therapies are summarized (Table). MEK-inh-based therapy was administered to 3 (37.5%) patients as a first or second-line treatment, and to 5 (62.5%) patients as a third to fifth-line treatment for metastatic PDAC. The overall survival and progression free survival (PFS) on MEK-inh-based therapy was 8.4 and 4.9 months, respectively. Four patients had PFS beyond 4 months (4.9, 5.5, 5.6 and 6.9 months).
Conclusions:
Individualized MEK-inh-based therapy demonstrated efficacy in late-line treatment of metastatic PDAC with
KRAS
G12R alterations. Using this approach earlier in the treatment course and in combination with RAS inhibitors or cytotoxic systemic therapies may further enhance outcomes.

Tumor alterations and matched therapies.

Gene altered
Number of patients (%)
Number of patients matched (%)
Drug family matched

KRAS G12R

8 (100)
8/8 (100)
MEK inhibitor

TP53

7 (87.5)
4/7 (57)
VEGF/VEGR inhibitor*

CDKN2A

4 (50)
4/4 (100)
CDK4/6 inhibitor**

SMAD4

2 (25)
2/2 (100)
MEK inhibitor + (EGFR or Pan-HER inhibitor)***

*PMID: 27466356; **PMID: 33472910; ***PMID: 36127339, PMID: 24625091.
Clinical outcomes of adjuvant chemoradiotherapy in pancreatic adenocarcinoma with R1 resection.
Authors: Wulaningsih Wahyu , Ah-Moye Amy , Khan Asadullah , Senthivel Nishanthi , Tait Diana M. , Chong Irene Yu-Shing , Hin Brian , Terlizzo Monica , Bhogal Ricky Harminder , Yeung Kai Tai Derek , Aitken Katharine
Published: January 2025

731

Background:
The benefit of chemoradiotherapy (CRT) following adjuvant chemotherapy in pancreatic cancer is unclear, though recent findings suggest some disease-free survival benefit over chemotherapy alone. We aimed to assess overall (OS) and progression-free survival (PFS) and patterns of disease recurrence following adjuvant chemoradiotherapy (CRT) in pancreatic adenocarcinoma patients with R1 resection (defined as <1mm).
Methods:
We retrospectively collected data of patients with pancreatic adenocarcinoma who underwent adjuvant CRT (50.4-54Gy) following surgery with R1 resection between 2007-2023 in a single centre in the UK. Clinical data was collected from electronic medical records and information on radiotherapy was collected from treatment planning systems (TPS). Toxicity during and after CRT was graded with Common Terminology Criteria for Adverse Events (CTCAE). OS and PFS were measured with Kaplan-Meier curves from the time of surgery to death or disease progression or last follow up. In-field and locoregional recurrence were determined from restaging scans compared against radiotherapy field in TPS.
Results:
Among 33 patients included, 27 (81.8%) died within median follow-up 39 (14.8-111.4) months. All patients received adjuvant chemotherapy prior to CRT. Median OS was 42 (21.6-52.7) months and median PFS was 18.2 (15.5-28.4) months. In all but one patient, the R1 involved the posterior resection margin. Most patients (84.8%) had documented disease progression. In the majority the site of first progression was distant metastatic disease (51.5%), whilst six (18.2%) had local recurrence within the radiotherapy field. Four (12.1%) relapsed locoregionally. No statistically significance difference in OS or PFS was seen with presence of perineural or lymphovascular invasion, though analysis was limited by low number of patients. The majority of patients (72%) were node positive on pathology. Two (6.1%) patients had grade 3-4 toxicity during CRT (neutropenic and non-neutropenic sepsis).
Conclusions:
Our study supported acceptable safety following CRT as an adjuvant treatment in pancreatic cancer patients with R1 resection on surgery. Despite R1 resection, we observed survival outcomes with adjuvant chemotherapy and CRT somewhat above previously reported data. However the benefit of CRT after adjuvant chemotherapy remains unclear. Further evaluation is warranted to clarify which subgroups of patients benefit.
SIL-204 siRNA encapsulated in extended release microparticles for the treatment of localized cancer that harbors a KRAS G12x or G13D mutation.
Authors: Shirvan Mitchell , M Racheli , Yaron Michal , Zorde Elina , Shragai Orit , Maor Aloni Revital , Bernstein Adi , Shinar Doron , Nyska Abraham , Hadar Ilan , Peled Amnon
Published: January 2025

745

Background:
In a Phase 2 trial, treatment of non-resectable locally advanced pancreatic cancer (LAPC) patients harboring the KRAS G12D or G12V mutations, with SiG12DLoder combined with chemotherapy resulted in superior median overall survival (OS) of 9.3 months over chemotherapy (not statistically significant) and Objective Response Rate of 55% (35% over the chemotherapy control), when administered once every 3 months (Clinical trial # NCT01676259, ESMO 2023, abstract FPN: 1626). SIL-204 which is a modified version of siRNA siG12D is composed of a 21-base sense and 23-base antisense strands, both chemically modified and linked to a lipid. SIL-204 is encapsulated in biodegradable PLGA microparticles (MP), for direct release and injection into KRAS mutated solid tumors using an endoscopic ultrasound procedure. The strategy of preventing the synthesis of KRAS mutated protein may have an advantage over other approaches targeting KRAS function using small molecules.
Methods:
Methods are presented in results section.
Results:
SIL-204 has an increase stability over siG12D.To enhance stability, base modifications and phosphorothiate bonds at cleavage sites were implemented. SIL-204 exhibited a half-life of more than 48 hours in human serum. SIL-204 has robust KRAS silencing
.
When tested in Hepa1-6 cells transfected with individual human KRAS mutations, SIL-204 effectively silenced the various G12x mutations found in pancreatic cancer (D,V,R,C) at sub-nanomolar concentration (IC50 range=0.19-0.59) as well as G13D (IC50 =0.37). Addition of a hydrophobic tail to a prototype of SIL-204, SIL-101, increased the silencing of KRAS. Using PANC-1 cells (KRAS G12D mutation), lipid conjugation of the siRNA doubled the siRNA’s silencing efficiency in these cells. In addition, release of SIL-204 from the MP was tested in rats and indicates a prolong and sustained release over our intended treatment regimen SIL-204-MP was administered to tumors from human pancreatic tumor cell lines Capan-1 (KRAS G12V mutation and labelled with luciferase) grown in NSG mice and Panc-1 (grown in Athymic Nude mice). Bioluminescence imaging of tumor growth showed that SIL-204-MP significantly reduced Capan-1 tumor growth compared to vehicle controls, p<0.0005. Furthermore, histopathological analyses of tumor center slices from Capan-1 and Panc-1 models showed induction of significant tumor necrosis with SIL-204 compared to vehicle controls.
Conclusions:
The preclinical results of SIL-204-MP are promising and as the potential to further enhance the anti-tumor effect demonstrated by siG12DLoder in pancreatic patients. SIL-204 is now in toxicology studies as preparation for clinical trials in non-resectable pancreatic cancer.
Validation of PDACai v2.0 in predicting relative benefit from frontline FOLFIRINOX (FFX) and gemcitabine/nab-paclitaxel (GA) for patients (pts) with metastatic pancreatic cancer (mPDAC).
Authors: Pishvaian Michael J. , Blais Edik Matthew , Matrisian Lynn M. , Brody Jonathan R , Thach Dzung , de Arbeloa Patricia Miren , Rocha Flavio G. , Chuy Jennifer W. , Wadlow Raymond Couric , Hendifar Andrew Eugene , Petricoin Emanuel
Published: January 2025

776

Background:
Novel biomarkers beyond genomic alterations in DDR pathway genes (e.g.
BRCA1/2
) have the potential to optimize frontline and subsequent treatment decisions for mPDAC. This real-world evidence (RWE) study validates PDACai v2.0, a machine learning framework that leverages clinical NGS data to predict progression-free survival (PFS) on FFX vs GA in individual pts with mPDAC.
Methods:
We analyzed outcomes from 774 pts with mPDAC who underwent genomic profiling via the Know Your Tumor program or were referred to Perthera by treating oncologists. Independent training and validation cohorts receiving either 1st line FFX or GA were split (60:40). PDACai v2.0 integrates an updated set of clinical (age < 63, sex) and lab-agnostic molecular features derived from genomic testing reports (specific
KRAS
variants,
TP53
GOF vs LOF, DDR pathway redefined). Relative benefit scores predicted by FFX or GA models were evenly binned into three PDACai signature categories representing lower, middle, and upper tertiles for each independent cohort. Statistical differences in median PFS were evaluated using ordinal Cox regression.
Results:
Median PFS followed PDACai predicted trends for each therapy’s training and validation cohorts. The predictive utility of PDACai was confirmed in the independent validation cohorts when comparing PFS on FFX (p = 0.01637; HR = 0.73 [95% CI: 0.56-0.94]) and GA (p = 0.0007506; HR = 0.62 [95% CI: 0.47-0.82]) across tertiles.
Conclusions:
Using RWE, the PDACai v2.0 signature successfully predicted PFS differences in pts treated with 1st line FFX or GA in mPDAC. Prospective validation efforts and additional data-driven insights into 2nd line PFS on FOLFOX vs 5FU/nal-irinotecan are underway.

Summary of actual PFS in months on 1st line therapies in pts assigned to lower, middle, and upper thirds based on relative PDACai v2.0 scores.

Independent Cohort (# Pts)
Lower TertilemPFS [95% CI]
Middle TertilemPFS [95% CI]
Upper TertilemPFS [95% CI]

1st line FFX Training (243)
6.5 [5.5-8.1]
9.3 [6.5-13.3]
15.8 [14.1-N/R]

1st line FFX Validation (165)
9.4 [7-13.3]
8.6 [5.6-11.4]
13.2 [9.9-39.6]

1st line GA Training (218)
5.6 [4.7-6.3]
6.9 [5.2-8.2]
11.2 [8.8-13.4]

1st line GA Validation (148)
5.6 [4.2-8.4]
7.5 [6.5-13.1]
8.5 [7.7-11.5]
Clinical outcomes of malignant portal vein thrombosis in patients with pancreatic cancer: A retrospective analysis.
Authors: Iqbal Rabia , Kimball Henry , Peshin Supriya , Zafar Maha , Sinha Samridhi , Colon Ramos Ana , Ullah Asmat
Published: January 2025

784

Background:
Portal vein thrombosis (PVT) includes portal vein blockage with a blood clot. Recently, there has been an increase in the incidence of PVT with solid malignancy. Portal vein thrombosis (PVT) is a potentially high-risk complication associated with pancreatic cancer. A hypercoagulable state is frequently observed in pancreatic cancer, with the incidence of thromboembolic events reported to range between 17% and 57%. We wanted to analyze the prevalence of PVT in patients with pancreatic cancer and its impact on hospital outcomes.
Methods:
We performed a retrospective analysis using the National Inpatient Sample Database (NIS) from 2018 to 2020. Patients with the primary diagnosis of pancreatic cancer and age >18 were diagnosed using ICD-10 codes. They were then stratified based on the presence of portal vein thrombosis. The Chi-square test was used to analyze categorical variables, and the T-test was used to analyze continuous variables. The confounders were adjusted using multivariate regression analysis. We observed the outcomes on mortality, length of stay, and total hospital charges.
Results:
A total of 336894 patients were diagnosed with a primary diagnosis of pancreatic cancer. Of them, 0.04% (n=13475 patients) were diagnosed with metastatic portal vein thrombosis. The mean age of the patients was 64 years (p <0.001). Out of them, 47% of patients were female. In comparison, the remaining 53% were male (p-value: 0.5). Almost 71% f the patients were White, 13% were African American and 0.09% were Hispanics (p-value <0.001). The presence of PVT was found to be associated with increased mortality in pancreatic patients (aOR 1.6, p-value <0.001) as compared to those without PVT. It was also associated with an increase in mean length of stay (LOS)(7.1 vs 6 days, p-value 0.009) and total hospital charges ($86,000 vs $73794, p-value <0.001). It was also observed that the presence of PVT was associated with increased odds of secondary outcomes, including venous thromboembolism (p-value <0.001), stroke (p-value 0.5), and acute kidney injury (p-value <0.001).
Conclusions:
The presence of portal vein thrombosis (PVT) in pancreatic cancer patients is associated with significantly worse hospital outcomes. These findings emphasize the importance of early detection and aggressive management of PVT in this patient population.

Comparison of hospital outcomes between pancreatic cancer patients with and without portal vein thrombosis.

Hospital Outcomes
Pancreatic cancer patients with PVT
Pancreatic cancer patients without PVT
Adjusted Odds Ratio (aOR)
95% CI
P-value

Mortality
9.4% (n=1310)
7.2% (n=23300)
1.3
0.3-1.5
<0.001

LOS (Days)
7.1
6.0
1.6
1.1-2.3
0.009

Venous thromboembolism (VTE)
11% (n=1645)
4.2% (n=13734)
2.9
2.5-3.3
<0.001

Stroke
0.03% (n=5)
0.02 (n=79)
1.8
0.2-14
0.5

Acute Kidney Injury
21% (n=2970)
20% (n=68499)
1.2
1.09-1.3
<0.001
TROP2 expression in small bowel adenocarcinoma: A potential target for novel therapeutic strategies.
Authors: Fujii Hiroyuki , Shoji Hirokazu , Hirano Hidekazu , Hirose Toshiharu , Okita Natsuko Tsuda , Takashima Atsuo , Kato Ken
Published: January 2025

799

Background:
Small bowel adenocarcinoma (SBA) is a rare cancer with limited chemotherapy options. To explore TROP2 as a potential therapeutic target for SBA and develop new treatment strategies, we examined TROP2 protein expression in SBA and analyzed associated clinicopathological features and prognosis, including PD-L1 expression levels in the same tumor samples from our previous studies.
Methods:
We retrospectively reviewed patients diagnosed with SBA who underwent adjuvant or palliative chemotherapy between July 2010 and July 2023 at our hospital. Immunohistochemistry staining of TROP2 (clone: SP295) was performed for pathological samples. The intensity of TROP2 membranous staining in tumor cells was classified as 0 (absent), 1 (weak to moderate), or 2 (strong). TROP2 positivity was defined as intensity 1 with ≥ 50% expression or intensity 2 with ≥ 10% expression. We also assessed overall survival (OS) in patients receiving palliative chemotherapy to examine the association between prognosis and TROP2, excluding microsatellite instability-high (MSI-H) patients treated with immunotherapy.
Results:
Pathological samples and clinical data were available for 51 patients. The median age was 63 years (range: 23–82), and 76% were male. Most patients (94%) had a performance status (PS) of 0–1. The primary lesion was in the duodenum in 49% of patients and in the jejunum or ileum in 51%. Surgery and adjuvant chemotherapy resulted in no recurrence in 12% of patients, while 88% received oxaliplatin-based palliative chemotherapy for unresectable SBA. Among those with unresectable SBA, 8% (4/51) had MSI-H and were treated with immunotherapy. TROP2 positivity was 84.3% (43/51). There were no differences in age, sex, or primary lesion between the TROP2-positive and TROP2-negative groups. In this cohort, the median CPS was 3 (range, 0–60). CPS was lower in TROP2-positive samples compared to negative samples (median CPS 7.9% vs. 23.4%,
p
= 0.030). However, all MSI-H cases were found to be TROP2-positive. Among patients receiving palliative chemotherapy, excluding those with MSI-H treated with immunotherapy, OS did not differ significantly between TROP2-positive and TROP2-negative patients (17.0 months vs. 9.2 months, HR 0.70,
p
= 0.480). Even after adjusting for age and PS, TROP2 expression was not identified as a prognostic factor.
Conclusions:
Our study highlighted that TROP2 is frequently expressed in SBA, suggesting it could be an effective therapeutic target for new treatment strategies. Further investigation is needed to confirm its potential.
Impact of next-generation sequencing in advanced gastrointestinal cancer.
Authors: Grover Aarushi , Makani Neeharika Srivastava
Published: January 2025

814

Background:
Next-generation sequencing (NGS) is a cutting-edge technology that allows for rapid DNA and RNA sequencing, identifying key mutations in cancer patients. It provides both diagnostic and predictive data for treatment decisions. Approximately 75.6% of US oncologists use NGS testing for patients with advanced solid tumors.This study retrospectively evaluates the impact of NGS testing on treatment outcomes for advanced GI cancer patients at a community-based cancer center in Florida.
Methods:
Between March 2019 and September 2023, 267 patients with stage 3 or 4 solid malignancies underwent NGS testing. Of these, 77 patients with advanced GI cancer were included in the study. Nearly half (48%) of the patients were diagnosed with advanced-stage colon cancer.NGS testing was performed using tissue samples (79.22%), blood samples (16.88%), or both (3.90%). Demographic and clinical outcomes, including time to diagnosis, treatment initiation, and survival, were collected and analyzed.
Results:
The median age of the study population was 70, with 88.31% of patients insured through Medicare. The cohort was composed of 61.04% males. Targetable mutations were identified in 59.74% of patients, leading to FDA-approved targeted therapies for 44.16%, and clinical trial eligibility for 79.22%. 52 patients were alive at the time of this analysis; those with biomarkers identified through NGS testing had a median treatment duration of 11 months regardless of whether testing impacted choice of therapy; whereas, patients without identified biomarkers had a median duration of 7.5 months. NGS testing impacted first-line therapy in only 6.49% of all patients; however, 80% of those patients were alive at the time of this analysis with a median duration of response of 5 months.
Conclusions:
NGS testing has become a cornerstone of oncologic care for advanced solid tumors; however, in this cohort of advanced GI malignancies, NGS results influenced first-line treatment decisions in only 6.49% of cases. Although the study included a small sample size, it reflects a real-world community setting where access to therapies and insurance coverage varies. For example, though patients may have targetable novel therapies available for their disease, the indications for such therapies may not be in the first line setting or covered by insurance. Advancements in NGS targeted therapies has greatly impacted the care of other solid malignancies such as non-small cell lung cancer; however, this study highlights that in the field of GI oncology, there is a large clinically unmet need of identifying newer biomarkers that are clinically relevant and impactful in earlier lines of oncologic care.
Uses of VEGF inhibitor bevacizumab in appendiceal adenocarcinoma.
Authors: McCullough Jacquelyn , Yousef Mahmoud M.G. , Yousef Abdelrahman M.G. , Shen John Paul Y.C.
Published: January 2025

831

Background:
Systemic treatment of metastatic appendiceal adenocarcinoma (AA) has been challenging due to a lack of well-established AA chemotherapy regimens and historical reliance on colorectal cancer (CRC) protocols. In the United States, but less commonly in Europe, bevacizumab is frequently incorporated in treatment of AA given its approved use for CRC. However, previously there have been no studies evaluating if there is a survival benefit attributable to bevacizumab in patients with AA.
Methods:
The Palantir Foundry system was used to extract data from the MD Anderson Cancer Center (MDA) electronic medical record for patients with biopsy-proven AA who received chemotherapy at MDA from 2015 to 2024. Only patients with complete staging and histopathology data were included in the analysis.
Results:
We identified 203 patients with AA who received chemotherapy at MDA and had complete tumor data. Of these, 43% (n=87) received bevacizumab at some point in their treatment. Patients who received bevacizumab were demographically similar to patients who received non-bevacizumab chemotherapy in terms of age at diagnosis, race, and sex; mucinous histology was more frequent in the bevacizumab cohort (52%, n=45 vs. 39%, n=45 in non-bevacizumab cohort). The 87 patients who received bevacizumab were treated with 1-6 lines of therapy per patient (mean = 1.57). The most frequently used bevacizumab-containing regimens were FOLFOX + bevacizumab (34%, n=46), FOLRIRI + bevacizumab (29%, n=40), 5-FU + bevacizumab (15%, n=21), and atezolizumab + bevacizumab (11%, n=15), with less common irinotecan + bevacizumab, TAS-102 + bevacizumab, and FOLFOXIRI + bevacizumab. Three regimens containing bevacizumab were discontinued due to complications: one instance of hand-foot syndrome attributed to xeloda, one instance of cardiomyopathy attributed to immunotherapy, and one bowel perforation with abdominal wall abscess attributed to bevacizumab. To determine if bevacizumab was associated with overall survival (OS) benefit we performed Kaplan-Meier analysis, with OS calculated from start of first line chemotherapy to death, in patients with metastatic AA who received either 5-FU doublet therapy alone or 5-FU doublet therapy with bevacizumab. Patients who received bevacizumab trended toward better OS (median 52 vs 25 months for doublet therapy alone, HR: 0.53, p= 0.059). The effect of bevacizumab was particularly notable in patients with signet ring cell histology; where bevacizumab use was associated with significantly longer OS (median OS 50 vs 14 months for doublet therapy alone, HR: 0.24, p= 0.034).
Conclusions:
Bevacizumab is frequently added to cytotoxic chemotherapy in the treatment of AA. These retrospective data suggest an OS benefit to adding bevacizumab to doublet chemotherapy, particularly in the case of signet ring cell histology.
The efficacy of anti-EGFR therapy across different lines of treatment in
RAS
wild-type left-sided metastatic colorectal cancer.
Authors: Archwamety Anita , Akewanlop Charuwan , Korphaisarn Krittiya
Published: January 2025

86

Background:
Anti-epidermal growth factor receptor monoclonal antibodies (anti-EGFR mAbs) are recommended as a first-line treatment in
RAS wild-type (RASwt
) left-sided metastatic colorectal cancer (mCRC). However, the efficacy of these therapies across different treatment lines remains unclear. This study aims to evaluate the efficacy of anti-EGFR mAb across first, second, third, and later-line treatments.
Methods:
We conducted a retrospective analysis of patients diagnosed with
RASwt
mCRC who received anti-EGFR mAb in all treatment lines at Siriraj Hospital between 2008 and 2023. The impact of anti-EGFR mAb treatment line on progression-free survival (PFS) and overall survival (OS) was determined using the Kaplan-Meier method and compared with the log-rank test.
Results:
Of the 350 patients with
RASwt
mCRC receiving anti-EGFR mAb, 33% (115 of 350) were treated in the first-line, while 16%, 45% and 6% were treated in the second-, third- and later-line settings, respectively. Eighty-six percent of patients had left-sided tumors, and anti-vascular growth factors were used in 34% of patients. The median follow-up time was 30.4 months (mo). Among patients with left-sided tumors, those receiving first-line anti-EGFR mAb treatment exhibited a significantly longer mPFS (11.9 mo, 95% CI 7.4-16.3, p<0.001). The mPFS in the second-, third- and later-line settings were 6.1 mo (95% CI 4.6-7.5), 4.9 mo (95% CI 3.8-6.0), and 5.1 mo (95% CI 2.3-7.9), respectively. There were no significant differences in terms of OS across treatment lines (p=0.27).
Conclusions:
Although first-line treatment with anti-EGFR mAb had the longest mPFS in left-sided mCRC, OS did not significantly differ among treatment lines. Therefore, anti-EGFR mAb can be incorporated as a part of therapy at any line of treatment.