bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship in gene amplification between
ERBB2
and other oncogenes: Implications for the therapeutic efficacy of trastuzumab (Tmab)-based chemotherapy (CTx) in HER2 positive gastric cancer.
Authors: Kadowaki Shigenori , Wakatsuki Takeru , Yamamoto Noriko , Ishizuka Naoki , Hironaka Shuichi , Minashi Keiko , Hirano Hidekazu , Shoji Hirokazu , Yamaguchi Toshifumi , Chin Keisho , Ogura Mariko , Nakayama Izuma , Osumi Hiroki , Ueki Arisa , Kitano Shigehisa , Boku Narikazu , Yamaguchi Kensei , Takahari Daisuke
Published: January 2025

468

Background:
This study aimed to elucidate the molecular characteristics, focusing on the co-amplification of
ERBB2
and other oncogenes, and to investigate their impact on treatment efficacy in HER2 positive GC.
Methods:
We conducted a phase 2 clinical trial (UMIN 00017602) evaluating the efficacy of S-1, oxaliplatin, and Tmab. Next-generation sequencing was performed using the TS-170 (Illumina).
Results:
32 patients were enrolled, of whom 6 (19%) were IHC2+/FISH+. The median progression-free survival (PFS) and overall survival (OS) were 11.8 and 28.8 months.
ERBB2
amplification with a cut-off value of 2.84 was present in 84.4% with a median copy number (CN) of 9.3 (range 2.4-76.6). Amplification of oncogenes other than
ERBB2
, such as
KRAS, FGFR2, MET,
and
CCNE1,
was observed in 87.5%, and the median CN of the highest CNs among oncogenes other than
ERBB2
was 7.8 (range 2.4-22.9). Eventually co-amplification was observed in 75%, and CNs of
ERBB2
and other oncogenes showed an inverse correlation (r=0.345, p=0.058). In all tumors having
ERBB2
CN ≥ 7.25 obtained by the ROC analysis, CN of
ERBB2
was the highest among oncogenes (
ERBB2
dominant). Conversely, in 92% of the tumors having
ERBB2
CNs < 7.25, CNs of oncogenes other than
ERBB2
was higher than ERBB2 (
ERBB2
non-dominant) (p<0.001). Moreover, the highest CN of the oncogenes other than
ERBB2
was higher in tumors with
ERBB2
CNs < 7.25 than that with
ERBB2
CNs ≥ 7.25 (median 12.6 vs 6.4 p=0.018). Patients with
ERBB2
non-dominant tumors showed significantly shorter PFS (median 6.9 vs 17.0 months, HR 6.40, p=0.001) and OS (median 14.8 vs 35.5 months, HR 2.72, p=0.016) and numerically lower response rate (63.6 vs 90.0%, p=0.151) compared with those with
ERBB2
dominant tumors.
Conclusions:
Most patients had co-amplification of
ERBB2
and other oncogenes, and the dominance of oncogene amplification in the tumor was associated with treatment efficacy of Tmab-based CTs in HER2 positive GC. These results suggest that the dominance of oncogene CNs within the tumor may determine tumor drivenness and influence treatment efficacy.
Blood TCTP as a biomarker associated with immunosuppressive features and resistance to immunotherapy in metastatic gastric cancer.
Authors: Kim Hyung-Don , Bang Yeong Hak , Hyung Jaewon , Yoo Changhoon , Yoon Myeong Jin , Lee Hayoung , Jeon Hyungsu , Yanai Hideyuki , Lee Gwanghee , Ryu Min-Hee
Published: January 2025

474

Background:
Cancer biomarkers are essential for determining the prognosis of the disease and/or predicting its response to specific treatments. However, established biomarkers representing specific myeloid cell populations and representative biomarkers in gastric cancer remain unavailable. Therefore, this study aimed to explore the prognostic and immunological relevance of plasma translationally controlled tumor protein (TCTP) in patients with advanced gastric cancer treated with immune checkpoint inhibitor (ICI) and cytotoxic chemotherapy.
Methods:
Plasma samples were prospectively collected from the cohorts of patients with gastric cancer who were treated with 1
st
line fluoropyrimidine plus platinum chemotherapy (n = 143, cohort 1) and 3
rd
line nivolumab (n = 165, cohort 2). Plasma TCTP levels were quantified using ELISA, and multiplex proteomic analysis (Olink) was conducted to assess expression levels of immune-related proteins. An external single-cell RNA sequencing (scRNA-seq) dataset was employed to validate the findings.
Results:
Patients with high plasma TCTP levels (TCTP-high group) exhibited poor survival outcomes with 1
st
line chemotherapy compared to those with low levels (TCTP-low group) in cohort 1. In the TCTP-high group, proteins associated with immunosuppressive myeloid cells, angiogenesis, and immune exclusion of T/NK cell function were upregulated, whereas proteins involved in T-cell activation/exhaustion were significantly upregulated in the TCTP-low group. The scRNA-seq analyses of myeloid cells revealed that TCTP pathway-associated genes (i.e.,
TLR2
,
CXCL1,
and
CXCL2
) were specifically expressed in immunosuppressive
APOE
+
macrophages,
THBS1
+
macrophages, and
CD1C
+
conventional type 2 dendritic cells. In the TCTP-high group, patients treated with nivolumab (cohort 2) also experienced poor survival outcomes.
Conclusions:
Plasma TCTP is a readily measurable prognostic biomarker, reflecting immunosuppressive signals of myeloid cells in patients with gastric cancer treated with ICI and chemotherapy.
Predictive role of circulating tumor DNA for locally advanced esophageal squamous cell carcinoma before surgery.
Authors: Kobayashi Ryota , Matsuda Satoru , Nakamura Kohei , Hoshi Yuki , Ho Keiso , Takeuchi Masashi , Fukuda Kazumasa , Nakamura Rieko , Kawakubo Hirofumi , Nishihara Hiroshi , Kitagawa Yuko
Published: January 2025

476

Background:
A precise preoperative tumor monitoring method that reflects tumor burden during neoadjuvant treatment is required to guide individualized perioperative treatment strategies for esophageal squamous cell carcinoma (ESCC). This study examined the clinical significance of preoperative circulating tumor DNA (ctDNA) in the plasma of patients undergoing neoadjuvant chemotherapy (NAC) followed by esophagectomy.
Methods:
Plasma samples were collected longitudinally for ctDNA analysis as well as genomic DNA from primary lesions from patients with histologically confirmed ESCC who received neoadjuvant chemotherapy (NAC) followed by subtotal esophagectomy. Next-generation sequencing was used to identify mutations in both the plasma and primary tumors. We evaluated the relation ship between ctDNA alterations and recurrence in patients with locally advanced ESCC.
Results:
Pretreatment samples from 25 patients (100%) showed the same mutations in both ctDNA and primary tumors; therefore, they were classified as ctDNA-positive before treatment. In the cohort of 25 patients analyzed, those who tested positive for ctDNA after NAC had a significantly higher risk of recurrence; the 36-month recurrence-free survival rates were 92% for ctDNA-negative patients and 8% for ctDNA-positive patients (p < 0.001).
Conclusions:
Preoperative ctDNA status may be a promising prognostic biomarker that can be assessed before surgery in patients with ESCC who received NAC. Expanded cohort validation will allow for more personalized multidisciplinary treatment approaches for ESCC tailored to ctDNA analysis.
Relationship between PD-L1 expression and the number of biopsy specimens in advanced gastric cancer.
Authors: Mizuno Taro , Narita Yukiya , Ishizuka Yasunobu , Sakakida Tomoki , Honda Kazunori , Masuishi Toshiki , Taniguchi Hiroya , Kadowaki Shigenori , Ando Masashi , Tajika Masahiro , Muro Kei
Published: January 2025

481

Background:
Programmed cell death ligand 1 (PD-L1) expression shows spatial heterogeneity in gastric cancer. Compared with single biopsies, multiple biopsies may provide reliable PD-L1 expression results. However, the optimal number of biopsy specimens remains unclear. This study aimed to assess the relationship between PD-L1 expression and the number of biopsy specimens in advanced gastric cancer.
Methods:
We retrospectively analyzed patients with advanced gastric cancer who received first-line chemotherapy at a single institution between December 2021 and June 2024. Those in whom PD-L1 expression was evaluated using tumor-containing biopsy specimens were included. PD-L1 expression was measured using the Dako PD-L1 IHC 28-8 pharmDx assay. PD-L1 positivity was defined as a combined positive score of ≥5. The association between PD-L1 positivity and the number of biopsy specimens was tested using the chi-square or Fisher’s exact test.
Results:
Of the 183 patients screened, 110 were included. The patient characteristics were as follows: median age, 71 (range: 34–87) years; sex (male/female), 75/35; primary site (gastric/gastroesophageal junction), 102/8; and histological type (diffuse/intestinal/other), 59/34/17. The PD-L1 positivity prevalence was 71.8%. In 97 patients, human epidermal growth factor receptor 2 (HER2) expression was detected in the same specimens as PD-L1, with a HER2-positive rate of 14.4%. The mean numbers of biopsy and tumor-containing biopsy specimens were 5.14 (range: 2–10) and 4.25 (range: 1–10), respectively. The PD-L1 positivity prevalence was significantly higher when the number of biopsy specimens was ≥5 compared with ≤4 (77.5% vs 56.7%,
P
=0.03; Table). The same trend was observed according to the histological type (diffuse type, 75.0% vs. 46.7%,
P
=0.04; intestinal type, 79.2% vs. 60.0%,
P
=0.39). In HER2-negative cases, PD-L1 positivity was significantly more prevalent when the number of biopsy specimens was ≥5 compared with ≤4 (83.6% vs 54.5%,
P
=0.006; Table). However, there was no such difference in HER2-positive cases (54.4% vs 66.7%,
P
=1).
Conclusions:
The data suggest that collecting at least five biopsy specimens increases the likelihood of identifying PD-L1 positivity in advanced gastric cancer, particularly in HER2-negative cases. This approach may improve PD-L1 evaluation accuracy and lead to better treatment decisions.

Relationship between the number of biopsy specimens and PD-L1 positivity.

Number of biopsy specimens
PD-L1 positivity (%)
PD-L1 negativity (%)

P
value

Overall

0.03

≥5
77.5
22.5

≤4
56.7
43.3

HER2-negative

0.006

≥5
83.6
16.4

≤4
54.5
45.5
Prognostic value of tumor regression grade (TRG) in patients with gastric/gastroesophageal junction cancer treated by peri-operative chemotherapy and surgery: A single-center experience (Institut Mutualiste Montsouris, Paris, France).
Authors: Lefèvre Antoine , Lefevre Marine , Bonnet Stéphane , Soularue Emilie , Colle Raphael , Ferraz Jean-Marc , Bennamoun Mostefa , Joulia Marie-Liesse , Malka David , Soubrane Olivier , Vernerey Dewi , Henriques Julie , Louvet Christophe
Published: January 2025

486

Background:
Management of locally advanced gastric and gastroesophageal junction (GOJ) cancer relies on peri-operative chemotherapy and radical surgery. Response to neoadjuvant chemotherapy can be evaluated by Mandard Tumor Regression Grade (TRG) performed on the removed specimens. The aim of this study was to investigate the prognostic value of TRG, in terms of post-surgical disease-free survival (DFS) and overall survival (OS).
Methods:
Retrospective analysis of all consecutive patients (Jan 2010 to Dec 2021) who underwent oncological gastrectomy for gastric or GOJ adenocarcinoma after neoadjuvant chemotherapy was performed. TRG was evaluated according to Mandard classification, ranging from 1 (complete pathological response) to 5 (absence of response), TRG 1-2 being considered as “good responders” and TRG 3-5 as “bad responders”. Univariate and multivariate analysis were performed for DFS and OS.
Results:
One hundred and ninety-nine patients were included, 157 treated with FOLFOX and 42 with FOLFOX + Taxanes (either FLOT or FOLFOX + Abraxane). TRG 1-2 was observed in 30% in patients (pts) treated with FOLFOX and 24% in pts treated with FOLFOX + Taxanes. With a median follow-up over 5 years (yrs), median DFS and OS were not reached (DFS rates at 3, 5 and 10yrs of 66.5%, 64.1% and 55.7%, respectively; OS rates at 3, 5 and 10yrs of 75.6%, 66.8% and 60.4%, respectively). In univariate analysis, TRG 1-2 was significantly associated with favorable outcome compared to TRG 3-5 in terms of DFS (HR 2.4, p-value 0.0056) and OS (HR 2.6, p-value 0.0061), as well as ECOG at diagnosis (0 vs. 1), ypT stage (yp T0-2 vs. yp T3-4), ypN stage (ypN- vs. ypN+), tumor localization (antrum + body vs. cardia + esophagus), and lymphatic, vascular and peri nervous embolisms (negative vs. positive) for both DFS and OS. However, in multivariate analysis (selection backward Cox-model), only ypT stage and vascular embolisms for DFS, and ypT and ypN stages for OS were found to be independent prognostic factors.
Conclusions:
Although TRG is a prognostic factor in patients with gastric or GOJ cancer, it does not appear as an independent factor for DFS and OS in this series of 199 pts. These results raise the issue of “good responder” definition, especially for TRG 3. Prognostic impact of TRG needs to be investigated for patients treated with combination of immune checkpoint inhibitors and chemotherapy in neoadjuvant regimens.
SOX/FOLFOX+nivolumab followed by conversion surgery for HER2 negative primary gastric or gastroesophageal junction cancer with oligo-metastasis or borderline resectable tumors: Early results of a consecutive 41 cases.
Authors: Nishino Masashi , Yoshikawa Takaki , Shoji Hirokazu , Fujisaki Yurina , Ogawa Rei , Wada Takeyuki , Hayashi Tsutomu , Yamagata Yukinori , Seto Yasuyuki
Published: January 2025

487

Background:
Gastric or gastroesophageal junction cancer with oligo-metastasis or borderline resectable tumors could be cured by conversion surgery after primary chemotherapy. Because SOX/FOLFOX plus Nivolumab showed high clinical response regardless of CPS score, this nivolumab-based chemotherapy followed by surgery may be promising strategy for these tumors.
Methods:
The study examined the patients who had HER2 negative primary gastric or gastroesophageal junction cancer with synchronous oligo-metastasis or borderline resectable tumors. Oligo-metastasis was defined as peritoneal dissemination localized to the upper abdomen, para-aortic lymph node metastasis, liver metastasis limited up to 3 segments, mediastinal lymph node metastasis, ovarian metastasis, or esophageal intramural metastasis. Borderline resectable tumors were defined as regional lymph node metastasis forming bulky mass or primary tumors invading adjacent organs. The patients with these tumors were treated with primary chemotherapy with SOX/FOLFOX plus Nivolumab for 3 to 22 months, then were proceeded to conversion surgery in case the tumors are responded to chemotherapy and are considered to achieve R0 resection based on the MDT conference.
Results:
During November 2021 and February 2024, 41 consecutive patients were included in the study. Disease status was peritoneal dissemination in 1, para-aortic lymph node metastasis in 26, liver metastasis in 5, mediastinal lymph node metastasis in 1, ovarian metastasis in 1, esophageal intramural metastasis in 2, bulky nodal metastasis in 6, and primary tumors invading pancreas in 1 (distant oligo-metastasis in 34 patients and borderline resectable in 7). CPS score was >5 in 13, 5> and >1 in 23, and >1 in 5 patients. Chemotherapy regimen was SOX+Nivo in 38 and FOLFOX+Nivo in 3. Of 41 patients, 33 (80.5%) (SOX+Nivo: 30, FOLFOX+Nivo: 3) were proceeded to the conversion surgery, and 32 patients achieved R0 resection. 6 patients showed disease progression and 2 patients were judged as unresectable. Major pathological response (disappearance more than 80% of the primary tumor) rate was 54.5% (18/33) and pCR rate was 33.3% (11/33).
Conclusions:
SOX/FOLFOX plus Nivolumab for HER2 negative gastric or gastroesophageal junction cancer with oligo-metastasis or borderline resectable tumors achieved a high R0-conversion surgery rate and pathological response rate.
Definitive local therapy in solitary liver metastatic anal squamous cell carcinoma.
Authors: Siripoon Teerada , O'Donnell Conor , Storandt Michael H. , Starlinger Patrick , Tran Nguyen H. , Atwell Thomas D. , Jethwa Krishan , Jin Zhaohui
Published: January 2025

5

Background:
Metastatic anal squamous cell carcinoma is rare and associated with a poor prognosis. There is limited evidence on the impact of local interventions on survival outcomes in patients with metastatic disease. We aimed to evaluate the survival of patients with liver-only metastatic anal cancer following definitive local management of liver lesions.
Methods:
This is a single-institution retrospective cohort study of patients with liver-limited metastatic anal cancer who underwent curative-intent local therapy. Clinical characteristics were collected and analyzed. The Kaplan-Meier method was used to calculate disease-free survival (DFS) and overall survival (OS). Prognostic factors associated with DFS and OS were assessed using Cox-proportional hazards models.
Results:
Twenty-five patients were included, median age was 59 years, and 92% were female. None of the patients had known HIV infection, 92% had HPV-positive disease and 76% had metachronous liver metastases following locoregional disease. All patients received chemoradiation for the primary lesion Unilobar hepatic involvement was present in 76% of the patients, with 56% having a single metastatic lesion. Pre-intervention systemic therapy was provided to 52% of the patients, including 8 who received carboplatin and paclitaxel, with a median duration of 3 months and ORR of 69%. Definitive treatment of metastatic disease included surgical resection (60%), non-surgical interventions (20%), and multimodal therapy (20%). All patients had viable tumor in the pathological specimen. With a median follow-up of 22 months, median DFS was 7.3 months, and median OS was 51.3 months. An ECOG performance status of 2, poorly differentiated histology, and extrahepatic recurrence were identified as significant prognostic factors in the univariate analysis, but not in the multivariate analysis.
Conclusions:
Our results demonstrate potential for long-term survival in liver-limited metastatic anal squamous cell carcinoma amenable to local therapeutic intervention combined with systemic therapy. These findings warrant further prospective study of local therapy in oligometastatic anal cancer.

Characteristics
N=25 (%)

Median number of liver metastases (range), lesions- 1- 2-3- >3
1 (1-20)14 (56)8 (32)3 (12)

Median maximal diameter of liver metastases (range), cm
3 (0.9-11.9)

Best response of liver metastases to chemotherapy (N=13)- Complete response- Partial response- Stable disease- Progressive disease
2 (15)7 (54)3 (23)1 (8)

Surgical procedure (N=20)- Right/left hemi-hepatectomy- Segmentectomy- Wedge resection
4 (20)14 (70)2 (10)

Non-surgical procedure (N=10)- Local ablation- Radiotherapy- Other
5 (50)3 (30)2 (20)

Hepatic surgical margins (N=20)- Positive margins- Close margins (<1mm)- Negative margins
02 (10)18 (90)

Recurrent disease- Yeso Intrahepatico Extrahepatic- No
20 (80)14 (70)6 (30)5 (20)
Communication of cancer biomarker testing results: What patients need.
Authors: Clauer Julie Saliba , Nesathurai Anne , George Manju
Published: January 2025

51

Background:
As colorectal cancer (CRC) biomarker testing becomes more widespread and important for treatment decisions, understanding testing results can improve patient engagement, shared decision-making, and facilitate clinical trial enrollment. Our experience in the online 12,000+ member CRC community COLONTOWN (CT), suggests that communication of biomarker results to patients is not ideal. To learn more, we surveyed CT members on their biomarker testing experience.
Methods:
An online survey posted in CT in September 2024 had questions on testing received (what was tested and how), test results experience (communication before testing and after results, patient understanding and resulting impact), suggested provider statements on biomarker results (statements patients prefer) and disease and respondent details.
Results:
Of 83 respondents, 70% had testing that included at least 3 common CRC biomarkers; the following are results from this group. Until receipt of results, 30% were unaware that biomarker testing was being done, and 56% first reviewed results without a clinician. Only 17% of respondents felt that nothing was lacking in the clinician communication of biomarker testing results. Upon receipt of biomarker test results, respondents’ feelings improved (30%,18%), did not change (63%, 55%) or worsened (7%, 27%) about treatment options and prognosis, respectively. Test results made 51% feel more confident in their care, and reduced stress for 25%, but increased stress for 39%, with 1/3 citing sub-par communication of results as at least partly driving the stress increase. The value of clear communication was evident, as the most appealing sample provider statements on results with no actionable biomarkers included confirmation of proposed treatment plan and clarity on non-actionable biomarkers. Not surprisingly, 58% learned the most about their biomarker results from COLONTOWN.
Conclusions:
Our survey highlights the gaps in communication of biomarker testing results and provides insights on what may improve them. The perceived value of biomarker test results for patients seem to go beyond actionability as traditionally defined. Context-specific, nuanced communication of “what the results really mean” and a discussion of its impact on patient experience needs to be part of clinician communication of test results. We plan to develop resources to help, and we implore clinicians and testing companies to consider our findings and make changes in how they share test results with patients.
Hepatocellular carcinoma: A 30-year trend analysis of global burden stratified by risk factors, and socio-demographic indexes.
Authors: Bhanushali Charmi , Babu Kalaivani , Rajarajan Srinishant , Bhanushali Vidhi , Seetharaman Kala
Published: January 2025

529

Background:
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related morbidity and mortality worldwide, driven primarily by chronic infections with Hepatitis B, Hepatitis C, and alcohol consumption. This study systematically examines global trends of HCC from 1991 to 2021, focusing on age-standardized mortality rates (ASMR) and Disability-Adjusted Life Years (DALYs) according to risk factors across Socio-Demographic Index (SDI) regions. By highlighting these patterns, the study provides insights into the interplay of socio-economic disparities and healthcare advancements on HCC trends.
Methods:
We utilized data from the Global Burden of Disease database to extract ASMR, and age standardized DALYs for HCC between 1991 and 2021. The data was stratified by etiology (Hepatitis B, Hepatitis C, alcohol consumption) and stratified across five SDI regions: low, low-middle, middle, high-middle, and high SDI.
Results:
The global HCC ASMR decreased by 4% from 1991 to 2021, with the largest reduction (20.4%) in low SDI regions. Hepatitis B-related HCC ASMR dropped by 16.3%, with reductions across all SDI groups. ASMR of Hepatitis C-related HCC remained stable globally but fell by 15.1% in low SDI regions. Alcohol-related HCC ASMR increased by 10% globally, with the highest rise in high SDI regions (24.5%), and NASH-related HCC ASMR increased by 26.7% globally, with a 42% rise in high SDI regions. Hepatitis B-related HCC DALYs decreased by 22.2%, with the sharpest declines recorded in high (31.4%) and low SDI regions (29%). Hepatitis C-related HCC DALYs saw a 8.8% global reduction, which was consistent across all groups. Alcohol-related HCC DALYs rose by 4.6% globally, with increases of 14.4% in high SDI and 20.5% in low-middle SDI regions. NASH-related HCC DALYs increased by 18.7%, with a 34.7% rise in low-middle SDI regions.
Conclusions:
The study reveals substantial progress in reducing the global burden of Hepatitis B- and C-related HCC, particularly in low SDI regions. This progress likely reflects advances in vaccination, antiviral treatments, and screening programs. However, the rising mortality and disability associated with alcohol- and NASH-related HCC, especially in high SDI regions, emphasize the growing impact of lifestyle-related risk factors. These findings underscore the need for tailored public health strategies to mitigate the increasing effects of these preventable risk factors on global HCC outcomes.
Financial toxicity in patients with newly diagnosed hepatocellular carcinoma.
Authors: Lee Seohyuk , Garita Esteban , Sucre Santiago , Juarez Juan Jose , Peters Mary Linton Bounetheau , Bullock Andrea J.
Published: January 2025

538

Background:
Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related deaths and has been associated with significant patient (pt) financial liability, however no study has yet examined pt-reported measures of financial toxicity (FT) in this population. We sought to assess pt-reported FT in newly diagnosed HCC and to identify pt-, disease-, and treatment-related factors associated with FT.
Methods:
Pts with HCC were recruited prior to treatment initiation during their initial visit at a multidisciplinary liver cancer clinic at a tertiary care center between January 2023-May 2024. The Comprehensive Score for Financial Toxicity-Functional Assessment of Chronic Illness Therapy (COST-FACIT), a validated survey for assessing financial distress in pts with cancer (range, 0-44; lower scores reflect worse financial wellness), was completed by participants during their initial visit. Sociodemographic (age, sex, race, ethnicity, primary language, insurance status, employment status, marital status, highest education completed, household income, living arrangement, home zip code), clinical (Barcelona Clinic Liver Cancer stage, performance status, age-adjusted Charlson comorbidity index, albumin-bilirubin score, presence and etiology of chronic liver disease, Child-Pugh grade, MELD-Na score), and planned treatment (surgery, liver-directed therapy, systemic therapy, clinical trial enrollment) characteristics were evaluated by questionnaires or medical record review. The EORTC QLQ-HCC18 was used to assess pt-reported quality of life (QOL). Area Deprivation Indices were calculated using pts’ home zip codes. Mean COST-FACIT scores were compared using two-sided t test for binary variables and one-way ANOVA for non-binary variables.
Results:
Among 47 pts enrolled, 35 (74%) completed the COST-FACIT survey. Younger age (<65 vs ≥65 yrs; mean, 20.3 vs 27.8; p=0.05), non-English primary language (non-English vs English; mean, 16.2 vs 26.7; p=0.04), less completed education (high school or earlier vs college or beyond; mean, 23.3 vs 32.0; p=0.02), and worse self-reported QOL (EORTC QLQ-HCC18 score ≥cohort median vs <cohort median; mean, 21.4 vs 29.2; p=0.02) were significantly associated with worse FT. Although not statistically significant, Hispanic ethnicity (Hispanic vs not Hispanic; mean, 16.1 vs 26.4; p=0.07), lack of employment (not employed vs retired vs employed; mean, 15.5 vs 29.4 vs 24.3; p=0.07), and no plan for liver-directed therapy (no vs yes; mean, 17.9 vs 26.7; p=0.07) trended towards worse pt-reported FT.
Conclusions:
Among pts with newly diagnosed HCC, significantly higher pt-reported FT is associated with younger age, non-English primary language, less completed education, and worse QOL. Efforts are underway to longitudinally follow our study cohort to assess the course of self-reported FT over 1-year follow-up as well as its associations with treatment response and survival.
Efficacy and safety of durvalumab plus tremelimumab for unresectable hepatocellular carcinoma in Thailand: A real-world multicenter observational study.
Authors: Korphaisarn Krittiya , Wirasorn Kosin , Tanasanvimon Suebpong , Thanasombunsukh Kijjakom , Maneenil Kunlatida , Thanestada Jirawat , Teeyapun Nattaya , Chindaprasirt Jarin , Sathitruangsak Chirawadee , Siripoon Teerada , Tiraswasdichai Phannin , Charonpongsuntorn Chanchai , Wanchaijiraboon Passakorn , Laosuangkoon Wannisa , Sunpaweravong Patrapim , Akewanlop Charuwan ,   TSCO GI groups
Published: January 2025

539

Background:
Durvalumab plus tremelimumab (Durva/Treme) andatezolizumab plus bevacizumab are preferable first-line therapy for unresectable hepatocellular carcinoma (uHCC). This study aimed to evaluate the efficacy and safety of Durva/Treme in real world setting.
Methods:
Fifty patients with uHCC who enrolled in the expanded access program (EAP) for Durva/Treme as the first-line treatment from 12 centers in Thailand were included. Analysis was assessed for objective response rate (ORR), survival, and adverse events. We also compared data with the HIMALAYA study.
Results:
Median follow-up time was 9.8 months. There were 24 patients alive and 26 patients deceased. The median age was 62 years. Majority of the patients were male (80%). Hepatitis B, C and non-viral cause were identified in 44%, 30%, and 26%, respectively. Ninety-two percent of patients had Child-Pugh A, while 8% had Child-Pugh B(7). Macrovascular invasion was found in 24% of cases. The full data on efficacy and safety were summarized in table below.
Conclusions:
To date,this is the largest real-world data of Durva/Treme in the first-line treatment of uHCC. Our study demonstrated that Durva/Treme was effective but had lower ORR and higher liver toxicities than what reported in the HIMALAYA study.

EAP (N=50)
HIMALAYA (N=393)

Response by RECIST1.1, n (%) CR PR SD PD Not evaluable
2(4)4(8)24(48)18(36)2(4)

12(3.1)67(17)157(39.9)157(39.9)
-

ORR (%)
12
20.1

DCR (%)
60
60.1

mPFS (range), mo
5.36(0.2-12.5)
3.78(3.7-5.3)

mOS (range), mo
NA
16.4 (14.2-19.6)

Adverse events, n (%)

A
ny grade

G
rade > 3

A
ny grade

G
rade > 3

Any AE Diarrhea Rash AST elevation ALT elevation Increase bilirubin Hypothyroidism Myocarditis Myositis
37(74) 3(6) 12(24) 23(46) 21(42) 8(16) 7(14) 1(2) 1(2)
12(24) 1(2) 0 6(12) 7(14) 4(8) 01(2) 1(2)
378(97.4)103(26.5) 87(22.4) 48(12.4) 36(9.3) 20(5.2) 47(12.1) --
196(50.5)17(4.4) 6(1.5) 20(5.2) 10(2.6) 3(0.8) 02(0.5) 3(0.8)
Shifting the paradigm: Early identification of colorectal cancer with C the Signs clinical decision support.
Authors: Dadhania Seema , Herrick Brian , Bakshi Bea , Raoof Sana , Haddad Tufia C. , Patel Tushar , Riaz Irbaz Bin , Payling Miles
Published: January 2025

54

Background:
The incidence of colorectal cancer is increasing rapidly, particularly amongst younger people. Despite a screening program being widely available, most patients are diagnosed with cancer through symptomatic presentation. Leveraging electronic medical records (EMRs) through clinical decision support platforms offers potential for identifying high-risk individuals before clinical suspicion develops. This study aims to explore the challenges associated with early colorectal cancer diagnosis and evaluate the effectiveness of the cancer case finding feature of a cancer management platform called C the Signs.
Methods:
A retrospective analysis was conducted using data from the Mayo Data Platform, comprising records of 894,275 patients, including 7,348 diagnosed with colorectal cancer. C the Signs was employed to identify patients at risk of colorectal cancer based on EMR data. Sensitivity and specificity analyses were performed to assess the platform's performance in identifying high-risk patients. Additionally, the study evaluated the temporal discrepancy in colorectal cancer diagnoses between those flagged by C the Signs and those detected by primary care physicians.
Results:
The C the Signs screening platform had a sensitivity of 93.8% and a specificity of 19.7% in identifying patients at risk of colorectal cancer. Notably, 29.4% of patients with colorectal cancer were identified as being at risk up to 5 years earlier by C the Signs compared to diagnoses made by primary care physicians, highlighting the platform's potential for early detection.
Conclusions:
Early identification of high-risk individuals holds promise for improving patient outcomes and reducing the burden of colorectal cancer. Whilst the specificity of the C the Signs platform for colorectal cancer is relatively low, the sensitivity is comparable to the most favorable rates reported for colonoscopy. In addition, if C the Signs was used in conjunction with a relatively cheap screening test such as Faecal Immunochemical Testing, this would significantly drive up the specificity whilst maintaining the sensitivity. Further studies are needed to assess its efficacy in conjunction with tests available in primary care.
Regorafenib combined with immunotherapy and prognosis of unresectable hepatocellular carcinoma.
Authors: Li Tianxiang , Cao Jingyu , Han Bing , Wang Song , Li Zixiang , Guo Yuan , Cai Jinzhen , Wu Liqun
Published: January 2025

541

Background:
To investigate the prognosis and influencing factors of patients with unresectable hepatocellular carcinoma (uHCC) receiving regorafenib in different treatment modes.
Methods:
A total of 227 patients with uHCC who received at least 2 cycles of regorafenib treatment in the Affiliated Hospital of Qingdao University between June 2018 and August 2022 were retrospectively collected through the Hospital Information System (HIS). 204 patients were finally enrolled by inclusion and exclusion criteria after screening.
Results:
The median follow-up was 25.9 (4.5-69.7) months. The median overall survival (OS) of 204 patients with uHCC was 27.7 (95%CI 21.98-33.42) months. The 1, 2, 3 and 5-year OS were 80.9%, 55.9%, 41.4% and 26.7%, respectively. Univariate analysis showed that combination with immune checkpoint inhibitor (ICI) and metabolic-associated complications were independent factors for survival benefit of regorafenib, while the Eastern Cooperative Oncology Group Performance Status (ECOG‐PS) scale = 2, undecreased Alpha-fetoprotein (AFP), macrovascular invasion and extrahepatic metastasis were independent risk factors for poor prognosis (P<0.05). Compared with 60 patients receiving regorafenib alone, 144 patients receiving regorafenib combined with ICI had a significant survival benefit (median OS, 16.9 vs. 31.5 months, respectively, P=0.006). The median OS of 153 patients receiving second-line therapy with regorafenib was 30.3 months. Among 51 patients receiving third or more lines of therapy with regorafenib, compared with 4 patients receiving regorafenib alone, 47 patients receiving regorafenib combined with ICI had a significant survival benefit (median OS, 9.4 vs. 24.1 months, respectively, P=0.000). Among 148 patients receiving local treatment, the median OS of patients with regorafenib combined with ICI (n=115) or without ICI (n=33) was 33.2 and 16.5 months, respectively (P=0.005).
Conclusions:
Regorafenib has a good prognosis in second-line treatment of uHCC. The OS of patients with regorafenib combined with ICI were significantly better than that of patients without ICI. The OS benefit of regorafenib combined with ICI was also equivalent in patients with third or more lines. The benefit of regorafenib combined with ICI was better for patients receiving local treatment.
Real-world assessment of MDM2 amplification and survival among patients with advanced or metastatic biliary tract cancer in the United States.
Authors: Iyer Renuka , Evans Kathryn , Klein Alyssa B , Shridharmuthy Divya , Stanhope Stephen , Nordstrom Beth , Sahai Vaibhav
Published: January 2025

544

Background:
There are few real-world studies on biliary tract cancer (BTC), especially those related to biomarkers for potential novel targeted therapies. The aim of this study was to provide additional information of the prevalence of biomarkers, treatment patterns, and clinical outcomes of patients with BTC in the US, with a focus on patients with mouse double minute 2 homolog (
MDM2
) amplified, tumor protein 53 wild type (TP53 WT) BTC.
Methods:
This was an observational cohort study using deidentified data from the Flatiron Health-Foundation Medicine BTC Clinico-Genomic Database, which included patients with advanced or metastatic BTC who underwent genomic analysis and received antineoplastic therapy in the US between January 1, 2013 and June 30, 2023. Three cohorts were created: 1) 1L+ cohort that included all patients that initiated 1
st
line (1L) therapy during the study period, 2) 2L+ cohort that included all patients that initiated 2
nd
line (2L) therapy during the study period, and 3)
MDM2
amp + TP53 WT cohort that included patients in the 1L+ cohort that had
MDM2
amplified (≥ 8 copies), TP53 WT. The prevalence of select biomarkers was assessed, as well as treatment patterns, and clinical outcomes including time to next therapy (TTNT) and overall survival (OS).
Results:
A total of 1,548 patients met the selection criteria for the 1L+ cohort, of whom, 875 initiated 2L therapy (2L+ cohort), and 55 had
MDM2
amplified, TP53 WT BTC (
MDM2
amp + TP53 WT cohort). In the 1L+ cohort, 66 (4.3%) had
MDM2
amplification and 872 (56.3%) had TP53 WT. The most common treatment regimens were cisplatin/gemcitabine (44.5%, 50.7%, 41.8% of patients in the 1L+, 2L+, and
MDM2
amp + TP53 WT cohorts, respectively) at 1L and FOLFOX (12.9%, 22.9%, 16.4% of patients, respectively) at 2L. The median (95% CI) OS from start of 1L was 10.7 (10.0 – 11.3) months for the 1L+ cohort and 11.9 (10.4 – 17.7) months for the
MDM2
amp + TP53 WT cohort. The median OS from the start of 2L was 8.0 (7.2 – 8.8) months for 2L+ cohort. Furthermore, the median TTNT was similar between 1L+ cohort and
MDM2
amp + TP53 WT cohort, 5.3 (5.0 – 5.7) and 4.8 (4.0 – 7.6) months, respectively. The median TTNT from the start of 2L in the 2L+ cohort was 4.3 (3.8 – 4.6) months. We will present co-mutation data in
MDM2
amp + TP53 WT cohort.
Conclusions:
The
MDM2
amplification and TP53 WT status does not appear to be a prognostic biomarker in advanced/metastatic BTC with similar median TTNT and OS in the 1L+ and
MDM2
amp + TP53 WT cohorts. Targeted treatments may help improve OS among these patients and thus further research into these treatments and how they impact survival is warranted.
Long-term follow-up of the randomized trial on open versus laparoscopic surgery for primary tumor resection in patients with non-curable stage IV colon cancer (JCOG1107).
Authors: Shiomi Akio , Akagi Tomonori , Kagawa Hiroyasu , Kajikawa Riku , Katayama Hiroshi , Fukuda Haruhiko , Ito Masaaki , Watanabe Jun , Ikeda Satoshi , Okajima Masazumi , Tsukamoto Shunsuke , Takashima Atsuo , Kanemitsu Yukihide , Inomata Masafumi
Published: January 2025

55

Background:
The Japan Clinical Oncology Group (JCOG) 1107 (UMIN-CTR: UMIN000009715) was a non-inferiority phase III trial to compare laparoscopic surgery (LAP) with open surgery (OP) for symptomatic, non-curable stage IV colon cancer, using progression-free survival (PFS) as the primary endpoint based on the intention-to-treat principle. The planned primary analysis confirmed the non-inferiority of the LAP over the OP. Additionally, the present study aimed to compare the LAP and OP using long-term 3-year follow-up data from the JCOG1107.
Methods:
Eligibility criteria included pathologically proven adenocarcinoma or adenosquamous carcinoma; primary tumor located at the cecum, ascending, transverse, descending, sigmoid, and rectosigmoid colon; primary tumor with bowel stenosis and/or bleeding; and having at least one to three non-curable factors. The sample size was 194 with a power of 70%, one-sided alpha of 5%, and non-inferiority margin of the hazard ratio (HR) of 1.38.
Results:
In total, 195 patients were randomized (OP 95, LAP 100) between January 2013 and January 2021. OP was performed in 92 and LAP in 98 patients. Postoperative chemotherapy was administered in 82 OP and 86 LAP patients. As the data cut-off date of Feb 2024, 93 (98%) and 100 (100%) PFS event occurred in OP and LAP. The 3-year PFS were 5.3% (95% CI, 2.0-11.0) and 3.0% (0.8-7.8) for OP and LAP arms, respectively (HR: 1.028, 95% confidence interval [CI]: 0.772–1.370; P for non-inferiority = 0.0222). Regarding OS, 87 (92%) and 90 (90%) death occurred in OP and LAP. The 3-year OS were 31.5% (22.5-41.0) and 28.5% (20.0-37.6) for OP and LAP arms, respectively (HR: 1.048; 95% CI: 0.780–1.410).
Conclusions:
Long-term follow-up data supported the non-inferiority of LAP over OP for primary tumor resection in patients with non-curable stage IV colon cancer. Our study findings indicate that LAP is acceptable as a standard treatment for symptomatic, non-curable stage IV colon cancer.
Clinical trial information: UMIN000009715
.
Risk of proteinuria with atezolizumab plus bevacizumab versus lenvatinib in first-line systemic treatment for hepatocellular carcinoma.
Authors: Yang JIwon , Choi Won-Mook , Kim Hyung-Don , Choi Jonggi , Yoo Changhoon , Lee Danbi , Shim Ju Hyun , Kim Kang Mo , Lim Young-Suk , Lee Han Chu
Published: January 2025

558

Background:
Proteinuria presents a challenging complication during systemic therapy for hepatocellular carcinoma (HCC). This study aims to identify risk factors for proteinuria in patients with HCC treated with atezolizumab plus bevacizumab (Atezo/Bev) or lenvatinib (LEN) as first-line systemic treatment.
Methods:
A retrospective analysis was conducted on 622 consecutive patients with unresectable HCC who received Atezo/Bev or LEN as first-line systemic treatment between October 2013 and October 2022. Cumulative incidence of proteinuria was estimated using Kaplan–Meier curves and compared using log-rank tests. Risk factors for proteinuria were identified using Cox proportional-hazard models, along with propensity score-matched and subgroup analyses.
Results:
Among 367 patients treated with Atezo/Bev and 255 with LEN, the cumulative incidence of proteinuria at 12 months was 27.5%. In the multivariable analysis, Atezo/Bev treatment (HR, 1.57; 95% CI, 1.03–2.42), diabetes (HR, 1.64; 95% CI, 1.03–2.61), Child–Pugh class B (HR, 3.43; 95% CI, 1.34–8.78), macrovascular invasion (MVI; HR, 1.58; 95% CI, 1.04–2.38), and an estimated glomerular filtration rate ≤60 mL/min/1.73 m
2
(HR, 3.21; 95% CI, 1.84–5.62) were identified as risk factors for proteinuria. A higher risk of proteinuria in Atezo/Bev patients compared with LEN was consistently observed in the PS-matched cohort, particularly pronounced in subgroups with MVI (HR, 2.84; 95% CI, 1.23–6.54) compared with those without MVI (HR, 1.31; 95% CI, 0.69–2.47).
Conclusions:
Patients treated with Atezo/Bev as first-line systemic treatmentfor HCC exhibited a higher risk of proteinuria compared with those with LEN, particularly when accompanied by MVI.
The impact of adherence to NCCN and BCLC treatment guidelines on survival in HCC: A single center study.
Authors: Alshammari Kanan , Almuntashri Manar , Alajmi Shahad , Alhwsawi Halah , Alsulami Taeef , Arabi Mohammad , Alolayan Ashwaq , Alkaiyat Mohammad , Shehata Husam , Algarni Mohammad Ahmad
Published: January 2025

561

Background:
Hepatocellular carcinoma (HCC) is a prevalent and lethal disease in Saudi Arabia, and globally. Guidelines such as Barcelona Clinic Liver Cancer (BCLC) and National Comprehensive Cancer Network (NCCN) are used to guide therapy for this disease. Adherence to these guidelines should lead to better outcomes. We aim to examine the adherence to guidelines and its impact on survival in a real world setting.
Methods:
This retrospective cross-sectional study was conducted at the Ministry of National Guard for Health Affairs, Riyadh, Saudi Arabia. Study included all adult patients with HCC who were diagnosed between 2020 and 2023, and presented at our HCC multidisciplinary tumor board (MDT). Data extracted included demographics, clinical and disease characteristics, treatment modalities, and survival status. Chi-square tests, and Kaplan-Meier survival analysis were used to explore relationships between tumor characteristics, adherence to NCCN and BCLC guidelines, and survival outcomes. Adherence to guidelines were assessed by two independent physicians.
Results:
The study included 208 patients with HCC, the majority were males (73%) with a mean age of 73 years. Less than half of the patients (41.7%) had an Eastern Cooperative Oncology Group (ECOG) performance status of 1. Tumor staging showed that 35% of the patients had BCLC stage D. Child pugh class A and B were equally present in 45% of the patients. Moreover, 24% of the patients had distant metastases or vascular invasion (in portal vein) placing them in BCLC stage C. It is noteworthy that Alpha-Fetoprotein (AFP) was abnormal (>8ng/ml) in 58% of the patients, 18% of them had AFP of more than 400ng/ml. Additionally, the prevalence of comorbid conditions were remarkable for liver cirrhosis being present in 85% of patients, while diabetes mellitus and hypertension each present in 63% of patients. Finally, survival analysis showed a median survival of 16.8 months in all patients with HCC (range 0-47.8 months). Adherence to guidelines were high, with 97.6% (n=203) following NCCN guidelines and 70.7% (n=147) following BCLC guidelines. Following both guidelines showed better survival with mean of 37 months (SD=1.841) in patients with child pugh class A (n=53), and mean survival of 24 months (SD=2.251) in patients with child pugh class B (n=74).
Conclusions:
Adherence to NCCN guidelines was high in our MDT presented patients compared to BCLC guidelines adherence which was lower, but with comparable survival outcomes.
Clinical outcomes of stereotactic body radiation therapy to the liver.
Authors: Kenney Lauren , Chen Yu-Hui , Howard Thomas , Bakhtiar Mina , Mamon Harvey J. , van Dams Ritchell
Published: January 2025

565

Background:
Stereotactic body radiation therapy (SBRT) can accurately and effectively target liver lesions with an ablative dose. However, prior studies suggest that SBRT directed at tumors near the central hepatobiliary tract may lead to downstream toxicity including biliary stricture and impaired liver function. This study aims to evaluate clinical outcomes and hepatobiliary toxicities associated with SBRT to the liver.
Methods:
This retrospective study reviews 177 patients who received CT- or MR-guided SBRT to the liver at Dana-Farber Cancer Institute and Brigham and Women’s Hospital from 2010 to 2024. Patient demographics, treatment characteristics, and clinical outcomes were extracted from electronic medical records. Local control, regional control, and overall survival were assessed using Kaplan-Meier methods. Toxicity was evaluated by tracking the incidence of biliary stricture requiring intervention and Child-Pugh (CP) scores pre- and post-SBRT.
Results:
Of the 177 patients, 47 (26.6%) had primary disease and 130 (73.4%) had metastatic disease, with a median follow-up of 58.7 months. Among those with primary disease, 9 (19.1%) had post-SBRT local progression (median time to progression not reached, 95% CI: 47.3, NA) and 26 (55.3%) had regional progression (median time to progression of 20.5 months, 95% CI: 6.5, 58.1). Of patients with metastatic disease, 44 (33.8%) had local progression (median time to progression of 40.2 months, 95% CI: 23.0, NA) and 96 (73.8%) had regional progression (median time to progression of 5.9 months, 95% CI: 4.8, 9.3). Median overall survival post-SBRT was 34.6 months for primary disease (95% CI: 20.2, 57.7) and 23.6 months for metastatic disease (95% CI: 19.0, 28.8). 18 patients (10.1%) later developed biliary stricture requiring intervention (12.8% of primary disease and 9.2% of metastatic disease). Of the 119 patients with CP scores available, 59 patients (49.6%) had a maximum post-SBRT CP score increase of 2 or more (55.0% of primary disease, 46.8% of metastatic disease).
Conclusions:
This study demonstrates that SBRT is an effective treatment option for local control in the liver, with better survival and progression outcomes for primary disease compared to metastatic disease. Among potential post-SBRT toxicities, initial analysis indicates frequent increase in CP score and low incidence of biliary stricture requiring intervention. An ongoing analysis will explore whether the dose to central bile ducts correlates with late strictures and toxicities.