tbuckley/cabot-search huggingface dataset:
A safety trial of antibiotic fecal microbiota transplantation for esophageal and gastric cancer patients treated with immune checkpoint inhibitors (Biorich2 trial).
Authors: Yuri Yoshinami, Hirokazu Shoji, Natsuko Tsuda Okita, Hiroyuki Takamaru, Toshiharu Hirose, Hiroshi Imazeki, Shun Yamamoto, Hidekazu Hirano, Atsuo Takashima, Kazuki Tanaka, Kana Ogawa, Shohei Koyama, Dai Ishikawa, Ken Kato
Journal: Journal of Clinical Oncology (2025)

TPS510 Background: The development of immune checkpoint inhibitors (ICIs) has improved the prognosis of unresectable advanced or recurrent esophageal and gastric cancer. However, the prognosis remains poor. The human intestinal microbiota plays various roles in digestion, immunomodulation, and metabolism and is known to influence tumor suppression. Previous studies reported that intestinal microbiota can impact immune responses and the effectiveness of ICIs. Therefore, this study investigates the safety and efficacy of antibiotic fecal microbiota transplantation (A-FMT) in patients with unresectable advanced or recurrent esophageal or gastric cancer. Methods: Eligible patients are diagnosed with unresectable advanced or recurrent esophageal squamous cell carcinoma or gastric adenocarcinoma. The primary endpoint is to examine the dose-limiting toxicity (DLT) of A-FMT. Secondary endpoints include response rate, disease control rate, progression-free survival, overall survival, and biomarkers of efficacy and adverse events. This trial consists of two parts: safety confirmation, which assesses DLT incidence, and an expansion part, which examines efficacy and safety. The safety confirmation part will enroll 3-6 patients in cohort 1 (combination therapy with ICIs and chemotherapy) and cohort 2 (combination of anti-PD-1 and anti-CTLA4 antibodies). The expansion part will enroll untreated patients: 10 for esophageal cancer (ICIs + chemotherapy), 10 for anti-PD-1 + anti-CTLA4 antibodies, and 11 for gastric cancer (ICIs + chemotherapy). After enrollment, patients receive antibacterial agents for 1 week before FMT. Patients then undergo total colonoscopy after bowel cleaning with polyethylene glycol plus ascorbic acid. A 200 mL fecal suspension from a healthy donor is transferred to the patient's cecum, and ICIs with/without chemotherapy are initiated thereafter. Biomarker analysis explores diagnostic or surrogate biomarkers, aiming to identify molecular targets, cell populations, microbial species, and functions involved in efficacy by analyzing the effects of A-FMT and ICIs on the tumor microenvironment and intestinal microbiota using methods such as proteome analysis. This trial is registered in the Japan Registry of Clinical Trials as jRCTs031240170 and was initiated in August 2024, with enrollment ongoing. Clinical trial information: jRCTs031240170.
Disparities in prophylactic tetracycline use among patients with metastatic colorectal cancer undergoing treatment with EGFR inhibitors.
Authors: Zach Rubnitz, Emma Braun, Amani Jridi, Vaia Florou, Ignacio Garrido-Laguna, Christopher Duane Nevala-Plagemann
Journal: Journal of Clinical Oncology (2025)

109 Background: Epidermal growth factor receptor (EGFR) inhibitors have been shown to improve survival in metastatic colorectal cancer and are considered a standard of care option for patients with RAS/RAF wild-type disease. However, anti-EGFR agents are associated with an acneiform rash that can lead to decreased quality of life and early discontinuation of treatment. Prophylactic doxycycline has been shown in a randomized clinical trial to decrease any skin toxicity ≥ grade 2 by 50%. In this study we sought to determine the rate of prophylactic tetracycline use in metastatic colorectal cancer patients receiving anti-EGFR therapy in the United States. Methods: The Flatiron Health Electronic Health Record-derived, de-identified database was used to analyze the records of patients who were at least 18 years old, diagnosed with metastatic colorectal cancer, and received treatment with an anti-EGFR agent (cetuximab or panitumumab). Patients were stratified by receipt of prophylactic tetracycline versus not. This was defined by an order for a tetracycline 28 days before to 1 day after initiation of an anti-EGFR agent. Demographic and clinical characteristics were compared via multivariable logistic regression. The change in percentage of patients who received a prophylactic tetracycline over time was assessed and was compared to the rate of anti-emetic prescription which served as a control to ensure drug administration data was accurately captured. Results: The records of 6,713 patients who met inclusion criteria and received an anti-EGFR agent between 2013 and 2023 were included in our analysis. A logistic regression model assessing the association between patient characteristics and the receipt of a prophylactic tetracycline suggested that older age, race (black/African American or Other), presence of RAS mutation, and higher line of therapy were all significantly associated with not receiving prophylactic tetracyclines. Other patient characteristics including gender, ECOG status, mismatch repair status, and RAF mutation status did not appear to impact the likelihood of receiving a prophylactic tetracycline. The rate of prophylactic tetracycline use increased from 10.9% in 2013 to 22.3% in 2023 while the rate of prophylactic anti-emetic remained stable at around 82%. Conclusions: This real-world analysis suggests the use of preemptive treatment for skin toxicity in patients with metastatic colorectal cancer who are treated with an anti-EGFR in US is suboptimal. Disparities in cancer care are also evidenced by lower use of tetracyclines in elderly and African Americans. Randomized controlled trials support the use of prophylactic tetracycline in these patients; thus, further research into the reason for this practice gap is necessary. Educational efforts should be undertaken to improve tetracycline prescribing rates in this population.
Chidamide plus envafolimab combined with S-1 as second-line treatment in advanced and metastatic pancreatic cancer (P-henomS/SCOG-P002): A single-arm, exploratory, multicenter, phase 2 trial—Interim report.
Authors: Wei Li, Kai Chen, Juan Du, Xiaofeng Chen, Deqiang Wang, Kang He, Caihua Xu, Mengyao Wu, Mengdan Xu, Bingyi Wang
Journal: Journal of Clinical Oncology (2025)

740 Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with poor prognosis worldwide. Chidamide, a subtype-selective histone deacetylase (HDAC) inhibitor, has significant anti-tumor effects and extensive synergistic effects with immunotherapy. Envafolimab is a light-chain deficient PD-L1 antibody. Here we conducted a single-arm, multicenter, prospective phase Ⅱ clinical study (ChiCTR2200058431) to evaluate the efficacy and safety of Chidamide plus Envafolimab combined with S-1 as second-line treatment in advanced and metastatic pancreatic cancer. Methods: Patients with metastatic PDAC receive Envafolimab (400 mg, on day 1), Chidamide (20 mg orally twice weekly, on days 0, 3, 7, and 10), and S-1 (40-60 mg according to body surface area, orally twice daily from day 1 to 14) every 3 weeks until disease progression, unacceptable toxicity, or patient refusal. The primary end points are safety and ORR. The secondary endpoints were PFS, OS, DCR, QoL and nutrition score. Results: Recruitment completed with 16 patients as of September 2023 and the data cut-off for analysis was August 2024, 13 were evaluable. Median age was 66 (range 59 - 80), with 5 males and 11 females. After a median follow-up of 8.5 months, the ORR and DCR by RECIST v1.1 were 30.77% and 76.92%, respectively. Median PFS was 5.83 months (95%CI 2.592-9.068) and median OS was not reached. No new safety signals were observed. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 31.25% of patients. The most common TRAEs were anemia (12.5%), decreased platelet count (6.25%) and neutropenia (12.5%). No treatment-related deaths occurred. Conclusions: Preliminary data suggest that Chidamide and Envafolimab in combination with S-1 may be an effective second-line treatment with a manageable safety profile for patients with PDAC. Clinical trial information: ChiCTR2200058431 . Efficacy evaluation. Efficacy Evaluation AII (N = 13) n(%) Best efficacy evaluation Partial Response (PR) 4（30.77%） Stable Disease (SD) 6（46.15%） Progressive Disease (PD) 3（23.08%） Objective response rate (ORR) 30.77% 95%CI 9.09-61.43 Disease control rate (DCR) 76.92% 95%CI 46.19-94.96 mPFS（95%CI） 5.83（2.592-9.068） mOS（95%CI） -（NR）
Preclinical development of the lipid nanoparticle–based mRNA vaccine with multiple natural T cell epitopes for pancreatic cancer.
Authors: Josephine Chang, Kevin Zheng, Yiming Li, Wanting Shan, Lei Zheng, Hai-Quan Mao, Juan Fu, Jiawei Zhou
Journal: Journal of Clinical Oncology (2025)

752 Background: Immunotherapy has recently emerged as a promising avenue in cancer treatment; however, its effectiveness on pancreatic ductal adenocarcinoma (PDAC) is hindered by the lack of effector T cells in the tumor microenvironment. One of the strategies to overcome the resistance of PDAC to immunotherapy involves identifying immunogenic tumor-associated and specific antigens for the development of personalized cancer vaccines. The mRNA platform has become an attractive platform for antigen presentation. The delivery of mRNA cancer vaccines via lipid nanoparticles (LNPs) enables intracellular delivery and controlled release of the payload, offering improved vaccine efficacy. However, mRNA vaccines presenting human T cell epitopes often lack a preclinical model for antitumor immune efficacy testing. Methods: A syngeneic mouse model of PDACs was established by implanting KPC tumor cells into the livers by hemispleen surgery. mRNA vaccine expressing five 25-mer peptide regions were synthesized. Two mouse CD8+ T cell epitopes were predicted. Their MHC binding was tested by the T2 binding assay. CD8+ T cells specific for these two epitopes were examined by ELISpot assays and were quantified by ImmunoSpot ELISpot Reader to identify changes in IFN-g secretion. Results: Using mass spectrometry analysis, we successfully identified natural HLA class I and class II-binding epitopes in the neoplastic tissues of human PDACs. For the design of mRNA vaccine, we chose five 25-mer peptide regions that each contains both class I and class II epitopes punctuated by AAY and GPGPG linkers and followed by an MITD sequence, which all aim to improve the efficiency of antigen presentation to dendritic cells. Using NetMHC, we predicted H2Kb or H2Db-binding epitopes LYPFPLAL and SMVQMTFL, within these five human peptide regions. The T2 binding assay showed a lack of evident binding of both peptides to the T2-Kb or T2-Db cells. However, the ELISpot assay showed that LYPFPLAL, but not SMVQMTFL, can induce the IFN-g expression from CD8+ T cells derived from splenocytes of the KPC tumor mice vaccinated by a peptide vaccine containing both peptides. Therefore, this result confirmed that LYPFPLAL is a mouse CD8+ T cell epitope and can be used to monitor antigen-specific CD8+ T cell response in response to the mRNA vaccine treatment in the syngeneic mouse model of PDACs. Conclusions: Antitumor efficacy of our above-designed mRNA vaccine can be tested in the syngeneic mouse hemispleen model of KPC tumors. Mouse LYPFPLAL epitope-specific CD8+ T cell response can serve as a surrogate marker for the antitumor efficacy of this mRNA vaccine in mouse models for PDAC.
Dose-escalated radiation for locally advanced unresectable pancreatic cancer.
Authors: Arjun K Moorthy, Steven Sckolnik, Amar Thosani, Albert Amini, Erkut Hasan Borazanci
Journal: Journal of Clinical Oncology (2025)

750 Background: Patients with unresectable locally advanced pancreatic cancer have limited therapeutic options. Historical treatments have included systemic chemotherapy or palliative radiation. New advanced radiotherapy treatment techniques have allowed dose escalated ablative radiotherapy to be delivered for patients with cancer limited to the pancreas. This study retrospectively reviews the long term outcomes of patients receiving dose escalated radiation for unresectable localized pancreatic cancer. Methods: Patients with locally advanced unresectable pancreatic underwent neoadjuvant chemotherapy with either gemcitabine or FOLFIRINOX based regimens. When maximum response was achieved with chemotherapy or this was no longer tolerated, patients were reassessed with imaging. Patients with localized unresectable disease then proceeded to definitive dose escalated radiation with either SBRT radiosurgery (40Gy in 5 fractions) or IMRT radiation (65-70Gy in 30-35 fractions) with concurrent 5FU. Surveillance of disease was performed with CT imaging and Ca19-9 biomarker assessment. Results: A total of 38 patients (21 male, 17 female) underwent definitive radiation. Radiation technique was determined by treating physician based on patient anatomy, with 7 patients having SBRT and 31 IMRT/5FU. Average patient age at diagnosis was 71. All patients underwent at least 6 months of follow up and mean follow up was 14 months. At time of latest follow up, 30 patients had no evidence of local progression and 12 patients had no evidence of progression at any site. The most common side effect at last follow up was grade 2/3 duodenal ulcer experienced by 7 patients. Conclusions: Advances in systemic chemotherapy have increased the population of patients with locally advanced unresectable pancreatic cancer who have persistent pancreatic disease after induction chemotherapy. Definitive dose escalated radiation is a new and effective technique to provide local control in this setting. This approach is well tolerated with manageable toxicity and effective durable local control. Patients continue to experience distant disease failure despite improving local control rates, though at a lower rate than historical controls. Control of primary pancreatic malignancy with dose escalated radiation can potentially improve quality of life and function for these patients for whom additional chemotherapy or surgery is not indicated.
Understanding the unmet needs in colorectal cancer: Insights from patient and survivor experiences.
Authors: Kimberley Lynn Newcomer, David A. Fenstermacher
Journal: Journal of Clinical Oncology (2025)

59 Background: Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer and the second leading cause of cancer-related deaths worldwide among men and women combined. Despite improved survival rates, there remains a gap in understanding the specific unmet needs of CRC patients and survivors. These needs include emotional support, information on treatment options, coping strategies, quality of life (QoL), and overall healthcare experience. The stress of a diagnosis is often compounded by the emotional and physical demands of treatment, which extend into survivorship when the disease is not active. Methods: The Colorectal Cancer Alliance launched a survey for colorectal cancer patients, survivors, and caregivers. This IRB-approved cross-sectional study, comprising more than 153 questions, aimed to inform on patient profiles, diagnosis experience, resources, QoL, access to care, and treatment experience. Participation in the survey was solicited from the Alliance network of social media, email, and web-based communities, underscoring the collective effort to understand and address the needs of CRC patients and survivors. Results: The survey included 283 participants, primarily aged 46-55. Key findings showed that 74% of participants had difficulty finding someone who understood their experience, and 41% reported reduced support from others after treatment ended. Additionally, 54% struggled with fatigue, and 51% coped with ongoing stress. CRC significantly impacted careers (64%), dating lives (51%), desire to have children (43%), relationships with spouses or partners (58%), sex lives (80%), and participation in social activities (65%). Although many felt informed before treatment, 46% reported unmet needs for information on complementary or alternative therapies. Conclusions: These results highlight the profound psychosocial and physical challenges faced by CRC patients and survivors, emphasizing the need for healthcare providers to develop tailored treatment and survivorship plans and comprehensive support services. Insights from this survey will guide the Colorectal Cancer Alliance (Alliance) in creating targeted actions, care programs, and support initiatives to address these needs. The Alliance aims to enhance patient care and improve CRC patients' and survivors' QoL, potentially reshaping the future of CRC management and survivorship care.
IMMULAB: A phase II trial of immunotherapy with pembrolizumab in combination with local ablation for patients with early stage hepatocellular carcinoma (HCC)—The IKF-IMMULAB trial.
Authors: Arndt Vogel, Oliver Waidmann, Thomas Christian Wirth, Mueller Tobias, Raphael Mohr, Gabriele Margareta Siegler, Thorsten O. Goetze, Enrico N. De Toni, Alexander B Philipp, Maria A Gonzalez-Carmona, Guido Hausner, Michael Geissler, Ludwig Fischer von Weikersthal, Angelika Kestler, Fabian Finkelmeier, Jorge Klagges, Regina Eickhoff, Salah-Eddin Al-Batran, Anna Lena Saborowski
Journal: Journal of Clinical Oncology (2025)

582 Background: Ablation of neoplastic tissue through radiofrequency ablation (RFA), microwave ablation (MWA), or brachytherapy is a potentially curative option for patients with early stage hepatocellular carcinoma (HCC); however, recurrence rates are high. While updated results from IMbrave050 do not support the use of adjuvant therapy following resection or local therapy, the potential of peri-interventional systemic treatment as a potentially more effective approach to increase recurrence free and long-term survival remains to be determined. We propose that peri-interventional treatment with pembrolizumab may improve outcomes following local ablative therapies. Methods: This single arm phase II trial investigates peri-interventional treatment with pembrolizumab combined with RFA/MWA or brachytherapy, or - as recommended for tumors ≥ 3 cm - by combination with TACE in early stage HCC with maintained liver function. 200 mg of pembrolizumab (q3w) was administered intravenously for 2 cycles followed by radiologic imaging and local therapy. Pembrolizumab was continued for up to 12 months. Primary endpoint was radiological response rate according to RECIST 1.1 prior to local therapy. Results: 30 pts (ECOG 0 or 1) were enrolled in 9 centers in Germany with a median age of 70 years (73.3% males, median tumor size 25 mm with minimum of 10 mm and maximum of 72 mm, 60% solitary lesions). All pts received at least 1 dose of study treatment and the median number of cycles was 13. ORR was 13.3% with 6.7% CR and 6.7% PR after two cycles. After a median follow-up of 34.5 months, median time to recurrence (TTR) was 16.43 months, with 8 pts remaining free of recurrence. mOS was not reached, with a 2y OS rate of 76% and a 3y OS rate of 66%. No new safety signs were observed. Subsequent local ablation was performed in 13 pts, and 10 pts started on systemic therapies (5 TKI, 3 ICI and 2 pts received TKI and ICI). Conclusions: In the IKF-IMMULAB trial the expected objective response rate of 30%, according to RECIST1.1., prior to local therapy was not reached. However, with recent evidence that radiologic response underestimates pathological response in ICI-treated HCC patients and supported by a 2y OS rate of 76% and a 3y OS rate of 66%, there is evidence for the efficacy of peri-interventional treatment with pembrolizumab without new safety signals. Clinical trial information: NCT03753659 .
Beyond Khorana score 2: Molecular correlates of venous thromboembolism in pancreatic cancer.
Authors: Jonathon Jonah Gerstein, Michelle Chan-Seng-Yue, Grainne O´Kane, Gun Ho Jang, Sandra Fischer, Anna Dodd, Spring Holter, Julie Wilson, George Zogopoulos, Maryam Monajemzadeh, Elena Elimova, Rebecca M. Prince, Raymond Woo-Jun Jang, Malcolm J. Moore, Jim Joseph Biagi, Faiyaz Notta, Robert C Grant, Steven Gallinger, Jennifer J. Knox, Erica S Tsang
Journal: Journal of Clinical Oncology (2025)

751 Background: Pancreatic ductal adenocarcinoma (PDAC) is associated with a hypercoagulable state leading to thrombosis. Risk models such as the Khorana score automatically classify PDAC as intermediate-high risk, and recent guidelines recommend consideration of thromboprophylaxis. However, little is known about the molecular correlates of PDAC for venous thromboembolism (VTE). Methods: We examined clinical and genomic data from the prospective multi-institution COMPASS trial (NCT02750657), which enrolled patients with treatment-naïve metastatic PDAC who underwent a fresh tumor biopsy for real-time whole genome and transcriptome sequencing. Laser capture microdissection was performed. Patients underwent restaging scans at 8-week intervals. Detailed chart review was conducted to focus on VTE risk factors, timing of VTE diagnosis, and anticoagulation. We also compared clinical and molecular factors based on timing of VTE diagnosis. Overall survival was defined as time from VTE to death. Results: Of 268 patients enrolled in the COMPASS trial, 166 patients had detailed clinical data available regarding VTE status. 82 patients (49%) developed a VTE, where 16 (20%) had breakthrough clots. Baseline epidemiological variables were similar for those with and without VTE, including no differences between age, sex, BMI, and baseline CA 19-9. No patients were on routine prophylactic anticoagulation. SMAD4 mutations were more frequently seen in the VTE subgroup (57% vs. 40%, p= 0.04), but no differences were seen in other driver genes (KRAS, TP53, CDKN2A), Moffitt subtype, or homologous recombination deficiency status. Patients who developed an early VTE (within 3 months) had a higher baseline CA 19-9 (median 4015 vs. 891, p= 0.02), and none were port-associated. A higher incidence of KRAS wildtype cases (10%) were observed in the early vs. later VTE groups (p= 0.03), but no differences in KRAS allelic status. There were no differences in burden of SNVs, indels, or SVs. Early VTE occurred in 46% of all basal cases, which are typically more aggressive, and only in 37% of classical subtypes. Overall survival was shorter with early VTE (HR 1.74, p= 0.02). Conclusions: A higher incidence of SMAD4 alterations were observed among patients with metastatic PDAC who developed VTE. VTE diagnosed earlier were associated with shorter survival, suggesting that early thromboprophylaxis should be considered at the time of diagnosis. Clinical trial information: NCT02750657 .