tbuckley/cabot-search huggingface dataset:
A multi-institutional retrospective study evaluating clinical outcomes and prognostic factors in patients with metastatic appendiceal adenocarcinoma.
Authors: Koshiro Fukuda, Atsuo Takashima, Hiroki Osumi, Takahito Awatsu, Akira Ooki, Hidekazu Hirano, Shota Fukuoka, Shohei Udagawa, Takeru Wakatsuki, Hirokazu Shoji, Keisho Chin, Mitsuhiro Fujishiro, Ken Kato, Narikazu Boku, Kensei Yamaguchi, Eiji Shinozaki
Journal: Journal of Clinical Oncology (2025)

69 Background: Appendiceal adenocarcinoma (AA), a rare cancer, has been reported to have high incidences of mucinous type histology, peritoneal metastasis, and relatively good prognosis. However, its chemotherapeutic efficacy and prognostic factors is not well known. Methods: We collected patients with metastatic AA treated with chemotherapy between February 2005 and March 2023 in two high volume cancer centers in Japan. We retrospectively analyzed the clinical outcomes of the chemotherapy of patients with metastatic AA and the clinical factors associated with treatment efficacy and prognosis by multivariate analysis. Results: A total of 66 patients with a median age of 54 years, were enrolled. 40 patients (60.6%) received an oxaliplatin-based regimen in combination with bevacizumab. The response rate was 22.0% and the disease control rate was 87.8%. With median follow-up period was 15.5 months [1.9-103.1], median progression-free survival (PFS) was 10.9 months [95% CI: 7.2-15.2] and median overall survival (OS) was 23.0 months [95% CI: 19.6-35.8]. 77.4% of patients received subsequent chemotherapy. In multivariate analysis, pretreatment carcinoembryonic antigen (CEA) and/or carbohydrate antigen 19-9 (CA19-9) were associated with significantly shorter PFS (HR: 2.93, P = 0.0049). Presence of primary tumor (HR:2.50, P = 0.015), ECOG performance status (PS) ≥1 (HR: 2.67, P = 0.0091), moderate to massive ascites (HR: 3.06, P = 0.0043) and high tumor marker levels (HR: 2.46, P = 0.026) were associated with significantly shorter OS. Classifying the patients by number of these prognostic factors for OS into three groups (0, 1-2, and 3-4), the group with prognostic factors (1-2 or 3-4) had a significantly shorter prognosis compared to the group without any these factors (0 vs 1-2: HR: 4.70, P = 0.038, 0 vs 3-4: HR: 17.6, P &lt; 0.01). In addition, the group with 3-4 prognostic factors had relatively lower rate of subsequent chemotherapy ratio than the group without these factors (66.7% vs 100%, P = 0.25). Conclusions: We confirmed our treatment outcomes were consistent with previous studies and elevation of tumor markers presence of primary tumor, ECOG PS ≥1, moderate to massive ascites were significantly associated with survival in patients with metastatic AA.
HCC in the Rio Grande Valley: Outcomes in a predominant Latino community.
Authors: Sergio Hernandez Llamas, Laura Reyes-Uribe, Edgar Lopez Pacheco, Fernando E. Membreno, José Cruz
Journal: Journal of Clinical Oncology (2025)

550 Background: Hepatocellular carcinoma (HCC) has slowly increased in the U.S. in recent years, with a higher incidence among racial and ethnic minorities, particularly Latinos. This retrospective study examines the different etiologies, presentation of diagnosis, management, and outcomes of patients presented in a multidisciplinary-liver tumor board in the Rio Grande Valley, home of 1.3 million Latinos. Methods: A retrospective chart review was conducted on patients with HCC diagnosis who were presented at the Liver Tumor Board of DHR Health Transplant Institute between 2017 and 2023. The data collected was extracted from the EHR, including medical history, laboratory results, and radiological studies required for staging, transplant eligibility assessments, clinical characteristics, and treatments. Results: A total of 250 cases were reviewed, and 70 patients with complete clinical data and a diagnosis of HCC were included in the study. Of those, 98.5% were identified as White/ Hispanic. The median age at diagnosis was 64.4 ± 9.2 years, with 72.9% male and 11.4% uninsured. The average BMI was 31.5 kg/m 2 , metabolic-associated liver disease (MALD) was present in 28.6% of patients, 25.7% were alcohol-related, and 38.6% presented multiple etiologies. A descriptive analysis of this population is found in the table. Ablative therapy was used in 68 (97.1%) of the patients. The number of patients sent for liver transplant evaluation was 31 (44%), and only 3 (4.2%) patients received a liver transplant. Barriers to transplant included lack of transportation, inadequate social support, underinsurance, and fear of the transplant itself. Conclusions: Our data by staging aligns with the national distribution of incidence cases from 2012-2022 per SEER program. The rate of transplantation at our institution is below the national average, highlighting the need to bridge this disparity and address race-specific barriers to transplant within the Latino community. Sociodemographic data. Parameter Stage IAN=15 (21.4%) Stage IBN=20 (28.6%) Stage IIN=10 (14.3%) Stage IIIAN=8 (11.4%) Stage IIIBN=9 (12.9%) Stage IVAN=5 (7.1%) Stage IVBN=3 (4.3%) All StagesN=70 (100%) Child Pugh A 7 (46.7%) 8 (40.0%) 5 (50.0%) 4 (50.0%) 2 (22.2%) 2 (40.0%) 1 (33.3%) 29 (41.4%) Child Pugh B 6 (40.0%) 6 (30.0%) 5 (50.0%) 2 (25.0%) 5 (55.6%) 2 (40.0%) 2 (66.7%) 28 (40.0%) Child Pugh C 2 (13.3%) 6 (30.0%) 0 (0.0%) 2 (25.0%) 2 (22.2%) 1 (20.0%) 0 (0.0%) 13 (18.6%) MELD-Na mean, (min-max) 12.8(7.0-21.0) 13.6(6.0-23.0) 12.8(6.0-20.0) 12.3(5.0-17.0) 13.6(8.0-26.0) 13.0(10.0-19.0) 11.3(7.0-14.0) 13.6(6.0-26.0) Therapy*:Ablative (TACE, Y90, Radiation, other) 15 21 10 6 8 6 2 Surgery (including transplant)** 1 1 2 2 2 0 0 Systemic 2 6 5 4 6 3 1 Overall Survival (months) 29.5 26.8 34.7 17.5 24.1 17.3 14.9 25.3 *Several patients received one or more types of therapy. **All transplant patients received ablation therapy.
Perioperative chemoimmunotherapy for patients with gastric or gastroesophageal junction cancer: A systematic review and meta-analysis.
Authors: Reo Omori, Yu Fujiwara, Kota Tokunaga, Takumi Sato, Sarbajit Mukherjee
Journal: Journal of Clinical Oncology (2025)

430 Background: Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis, in combination with chemotherapy, are known to improve survival in advanced/metastatic gastric (GC) or gastroesophageal junction cancer (GEJC). Therefore, several trials incorporated ICIs in the neoadjuvant/peri-operative setting with promising preliminary results. The purpose of this meta-analysis was to determine the safety and efficacy of neoadjuvant chemoimmunotherapy for resectable GC or GEJC. Methods: PubMed/MEDLINE and Embase were systematically searched for randomized control trials (RCTs) investigating the efficacy of neoadjuvant anti PD-1/PD-L1 ICIs for locally advanced GC or GEJC up to 07/27/2024. Outcomes of interest were surgical outcomes such as pathological complete response (pCR) rate and major pathological response (MPR) rate. Risk ratio (RR) with 95% confidence intervals (CI) were pooled using a fixed model meta-analysis. Statistical analysis was performed with Review Manager 5.4.1. I² statistics was used to assess heterogeneity. The Cochrane risk of bias assessment tool was used to assess the risk of bias. All analyses were conducted at a significance level of 0.05. Results: Seven RCTs comprising 2,911 GC or GEJC patients were included. Among these, 1,454 patients received neoadjuvant chemoimmunotherapy and 1,457 patients received chemotherapy, respectively. Neoadjuvant chemoimmunotherapy significantly improved pCR rate (RR 2.94; 95% CI 2.34-3.70; P&lt;0.00001; I 2 =33%), and MPR rate (RR 1.47; 95% CI 1.25-1.72; P&lt;0.00001; I 2 =30%) compared to chemotherapy alone. Chemoimmunotherapy was associated with slightly higher incidence of grade 3 or worse treatment-related adverse events than chemotherapy (RR 1.07; 95% CI 1.01-1.14; p=0.03; I 2 =0%). Conclusions: This meta-analysis showed that adding ICIs to chemotherapy significantly improved the pCR and MPR rates and was feasible for patients with locally advanced GC or GEJC. Results of survival outcomes in the included trials and ongoing trials are awaited to further determine the efficacy and utility of chemoimmunotherapy and identify patient populations that benefit from this strategy. Included studies. Author Year Trial# Design Cancer; Stage Name of IO Target Chemo regimen Extracted data pCR MPR TRAE Ding X 2023 NCT04982939 P2 G/GEJ; Stage2-3 Sintilimab PD-1 SOX ○ ○ Janjigian YY 2023 NCT04592913 P3 G/GEJ; ≥T2Nany/T0-4 N+ Durvalumab PD-L1 FLOT ○ ○ Li C 2023 NCT04208347 P3 G/GEJ; T3-4aN+ Camrelizumab PD-1 SOX(+apatinib) ○ ○ Lin JX 2024 NCT04195828 P2 G; T2-4N+ Camrelizumab PD-1 S-1+nabPTX ○ ○ ○ Lorenzen S 2024 NCT03421288 P2 G/GEJ; ≥T2 and/or N1 Atezolizumab PD-L1 FLOT ○ ○ Peng Z 2024 NCT04661150 P2 G/GEJ HER2+; resectable Atezolizumab PD-L1 CAPOX+Tmab ○ Shitara K 2024 NCT03221426 P3 G/GEJ; ≥T3N+ Pembrolizumab PD-1 FLOT or XP/FP ○ ○ Yuan SQ 2024 NCT04250948 P2 G/GEJ; T3-4N+ Toripalimab PD-1 SOX/CAPOX ○ ○ ○
Relationship in gene amplification between <i>ERBB2</i> and other oncogenes: Implications for the therapeutic efficacy of trastuzumab (Tmab)-based chemotherapy (CTx) in HER2 positive gastric cancer.
Authors: Shigenori Kadowaki, Takeru Wakatsuki, Noriko Yamamoto, Naoki Ishizuka, Shuichi Hironaka, Keiko Minashi, Hidekazu Hirano, Hirokazu Shoji, Toshifumi Yamaguchi, Keisho Chin, Mariko Ogura, Izuma Nakayama, Hiroki Osumi, Arisa Ueki, Shigehisa Kitano, Narikazu Boku, Kensei Yamaguchi, Daisuke Takahari
Journal: Journal of Clinical Oncology (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 &lt; 7.25, CNs of oncogenes other than ERBB2 was higher than ERBB2 ( ERBB2 non-dominant) (p&lt;0.001). Moreover, the highest CN of the oncogenes other than ERBB2 was higher in tumors with ERBB2 CNs &lt; 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.
Correlation between immune-related adverse events and clinical outcomes in patients treated with first-line nivolumab plus chemotherapy for advanced gastric or gastroesophageal junction cancer: A multi-center retrospective study in Japan.
Authors: Rin Inamoto, Nozomu Ogura, Misa Onishi, Yosuke Kito, Kengo Nagashima, Mitsuhiro Furuta, Nozomu Machida, Hirokazu Shoji, Naoki Takahashi
Journal: Journal of Clinical Oncology (2025)

439 Background: The CheckMate 649 trial and ATTRACTION-4 trial showed the efficacy of first-line nivolumab plus chemotherapy (Nivo-CT) for advanced gastric or gastroesophageal junction (GEJ) cancer. Recent studies have shown that immune-related adverse events (irAEs) caused by immune checkpoint inhibitors were associated with survival benefit in patients with solid tumors. However, there were few data on correlation between irAEs and efficacy of first-line Nivo-CT for advanced gastric or GEJ cancer. Methods: This multi-center retrospective study included patients with histologically confirmed advanced gastric or GEJ adenocarcinoma who were started on first-line Nivo-CT between December 2021 and December 2023. We divided the patients into two groups according to occurrence of irAEs; those with irAEs (irAE group) or those without (non-irAE group) and assessed the efficacy in both groups. Efficacy was evaluated by overall survival (OS), progression-free survival (PFS) and objective response rate (ORR). Landmark analysis at 2 months after initiating Nivo-CT was performed to adjust effects of early progression or death, in which patients who had events up to 2 months were excluded. Results: A total of 271 patients were included (median age, 70 [range 18–85] years; male/female, 64/36%; performance status (PS) 0/1/2, 47/49/4%; primary tumor site gastric/GEJ, 90/10%; status unresectable/recurrent, 81/19%; histology intestinal/diffuse, 30/70%; PD-L1 CPS &lt;1/1~5/&gt;5, 15/33/53%). Median follow-up time was 11.3 (range 1-30) months, and 80 (30%) patients developed irAE. In the landmark analysis, the median PFS was 11.1 months in the irAE group and 7.2 months in non-irAE group (HR 0.70 [95%CI 0.50-0.97], p = 0.034), and the median OS was 22.5 months in the irAE group and 17.9 months in non-irAE group (HR 0.77 [95%CI, 0.50-1.17], p = 0.219). The ORR were 67.4% in the irAE group and 66.7% in non-irAE group (p = 0.934). Multivariate analysis indicated that PS ≥1 (HR 1.66 [95%CI, 1.20-2.30], p = 0.02), elevated ALP (HR 1.61 [95%CI, 1.13-2.27], p = 0.008), and absence of irAEs (HR 1.55 [95%CI, 1.08-2.22], p = 0.018) were associated with poor prognosis. The most frequent irAEs were pneumonitis (n = 16), and grade ≥3 irAEs were observed in 26 (9.6%) patients: pneumonitis (n = 6), hepatitis/hypophysitis (n = 5). Conclusions: Development of irAEs was associated with improved outcomes in advanced gastric or GEJ cancer patients receiving first-line Nivo-CT.
Pembrolizumab and stereotactic radiotherapy combined in subjects with advanced HCC: A phase II study (PEMRAD).
Authors: Grainne M. O'Kane, Aruz M Mesci, Eric Xueyu Chen, Cynthia M Bocaya, Raymond Woo-Jun Jang, Ben X Wang, Rebecca M. Prince, Giselle M Boukhaled, Aisling S Barry, Mark Doherty, David K Wong, Lisa Wang, Anna Dodd, Laura A. Dawson, Jennifer J. Knox
Journal: Journal of Clinical Oncology (2025)

602 Background: Combination approaches of immune-checkpoint inhibitors and locoregional therapies have an increasing role in advanced HCC. Methods: The PEMRAD phase II trial investigated the efficacy of combination pembrolizumab and stereotactic body radiation (SBRT) following progression on sorafenib. Patients with advanced HCC, ECOG 0-1 and Childs-Pugh A were eligible. Patients received pembrolizumab on day 1 followed by SBRT starting Day 2 and delivered in five fractions. Pembrolizumab was continued every 21 days until progression, unacceptable toxicity or patient withdrawal. The primary endpoint was objective response rate (ORR) as measured by RECISTv 1.1. hypothesizing an increase to 40% with the combination. Tissue and liquid biopsies were collected for correlative analyses including multiplex IHC, longitudinal CyTOF and dynamic cytokine changes. Results: The trial was stopped early due to a shift in the treatment landscape. Between March 2018 and March 2023 18 patients of a planned 22 patients were enrolled and treated with combination therapy. Of these 10 (55%) had evidence of macrovascular invasion (MVI) and 15 (83%) had extrahepatic disease; viral hepatitis was the underlying etiology in 50%. The ORR was 41% meeting the proposed endpoint. Median number of cycles of pembrolizumab was 7.5 (2-35) .The median number of lesions treated by SBRT was 3 (1-5) and the median dominant gross tumour volume was 184 cc (IQR 69-285). The median PFS was 5.4 (2.8-9.9) months and median OS 12.6 (5.7-25.8) months. Of the 10 patients with macrovascular invasion 5 (50%) had evidence of a vascular thrombus response by RECIST criteria including 1 complete response. Treatment related adverse events ≥ grade 3 were reported in 5 patients (28%). One death due to myocarditis was attributed to treatment. Conclusions: In a poor prognostic group of patients in the second line setting, the combination of SBRT and pembrolizumab demonstrated high ORR and may have a specific role in patients with MVI. Correlative analyses will be presented at the meeting. Clinical trial information: NCT03316872 .
Perioperative adebrelimab combined with chemotherapy for locally advanced resectable esophageal squamous cell carcinoma: A single-arm, open-label, multicenter study.
Authors: Liang Dai, Yaya Wu, Ziqiang Tian, Jianqun Ma, Changhong Zhao, Bo Zhuang, Keneng Chen
Journal: Journal of Clinical Oncology (2025)

421 Background: Neoadjuvant programmed cell death 1 (PD-1) inhibitors combined with chemotherapy have shown promising results in treating locally advanced esophageal squamous cell carcinoma (LA-ESCC). However, relatively little attention has been focused on programmed cell death ligand 1 (PD-L1) blockades. This study aims to evaluate the efficacy and safety of neoadjuvant adebrelimab (anti-PD-L1 antibody) plus chemotherapy followed by adjuvant adebrelimab for resectable LA-ESCC. Methods: In this single-arm, multicenter study, patients (pts) with newly diagnosed, locally advanced resectable thoracic ESCC (cT1b-2, N+ or cT3-4a, N0/+) received 2 cycles of neoadjuvant chemoimmunotherapy with adebrelimab (1200 mg), paclitaxel (175 mg/m 2 ) and cisplatin (75 mg/m 2 ) every 3 weeks, followed by esophagectomy and 16 doses of adebrelimab. The primary endpoints were safety and pathological complete response (pCR) rate. Secondary endpoints included surgery completion rate, R0 resection rate, major pathological response (MPR) rate, event-free survival (EFS) and disease-free survival (DFS). The trial was registered at Chinese Clinical Trial Registry, identifier: ChiCTR2300069179. Results: Between May 2023 and January 2024, 36 pts met inclusion criteria, with a median age of 65 years (range: 42-73). Of these, 66.7% (24/36) were classified as stage III-IVa. As of August 1, 2024, the median number of treatment cycles for all pts was 7 (interquartile range, 2-12). The neoadjuvant therapy completion rate was 91.7% (33/36). Thirty-two pts underwent minimally invasive esophagectomy, resulting in an overall surgical resection rate of 88.9% and an R0 resection rate of 90.6%. The pCR rate was 15.6% (5/32) and the MPR rate was 31.2% (10/32). The EFS and DFS outcomes were not mature. During the preoperative treatment period, 35 pts (97.2%) experienced any grade of treatment-related adverse events (TRAEs). Grade 3 or 4 TRAEs occurred in 7 pts (19.4%), and there were no grade 5 TRAEs. The most common grade 3/4 adverse events included neutropenia (11.1%), leukopenia (5.6%), diarrhea (5.6%) and hyponatremia (5.6%). Surgical complications of grade 3/4 were reported in 7 pts (21.9%), with anastomotic fistula (6.3%) being the most common. No perioperative deaths occurred. Conclusions: Neoadjuvant adebrelimab combined with chemotherapy and adjuvant adebrelimab demonstrated encouraging clinical efficacy and manageable safety in pts with LA-ESCC. Further study is warranted. Clinical trial information: ChiCTR2300069179.
Not too much, not too little. Titrating flow rate to minimise inspiratory effort during helmet CPAP: A bench study
Authors: Andrea Coppadoro, Rosa Fracchia, Alice Nova, Andrea Restivo, Alberto Lucchini, Giacomo Bellani, Emanuele Rezoagli, Giuseppe Foti
Journal: Pulmonology (2024)

Non-invasive helmet respiratory support is suitable for several clinical conditions. Continuous-flow helmet CPAP systems equipped with HEPA filters have become popular during the recent Coronavirus pandemic. However, HEPA filters generate an overpressure above the set PEEP. A lung simulator was used to mimic patient respiratory mechanics and effort. Compared to room air spontaneous breathing, the additional inspiratory effort attributable to helmet CPAP (ΔPmusHelmet) was recorded at different continuous-flow rates (30-150 L/min), PEEP levels (5, 10, 12.5 cmH2O) and respiratory rates (15, 20, 25, 30 breaths/minute), both with and without a HEPA filter at the outlet port. Helmet pressure swings during inspiration largely explained ΔPmusHelmet variations (p<0.001, Spearman's Rho=0.964). The lowest ΔPmusHelmet levels (0.2 [0; 0.4] cmH2O) were frequently recorded (>70%) at a 90 L/min flow rate. Higher ΔPmusHelmet levels were recorded when the continuous-flow was lower than the peak inspiratory flow (3.7 [3.1; 5.6] cmH2O, p<0.001) or when a HEPA filter was used (2.7 [2.2; 3.5], p<0.001). Increasing the flow rate resulted in higher overpressure levels, particularly with a HEPA filter (p<0.001). Overpressure levels correlated with ΔPmusHelmet (p<0.001, Spearman's Rho=0.598). Helmet pressure swings below PEEP lead to additional inspiratory efforts. The HEPA filter acts as a flow resistor, generating an overpressure leading to increased respiratory effort. The continuous-flow rate should be titrated high enough to slightly exceed the peak inspiratory flow; however, further flow increase is not recommended as it leads to an increase in overpressure and helmet pressure swings below PEEP.