tbuckley/cabot-search huggingface dataset:
Automated radiomics model for preoperative pancreatic neuroendocrine tumor grade prediction.
Authors: Pratik Chandra, Naaz Nasar, Hadi Ghahremannezhad, Kevin Soares, Vinod P. Balachandran, Jeffrey A. Drebin, Michael Ian D'Angelica, T. Peter Kingham, William R. Jarnagin, Jayasree Chakraborty, Alice Chia-chi Wei
Journal: Journal of Clinical Oncology (2025)

655 Background: Pancreatic neuroendocrine tumors (PNETs) have varying biologic behavior based on factors including tumor grade. Many prognostic factors can only be determined post-pancreatectomy; thus, are unable to guide clinical decision making preoperatively. This is particularly relevant in small, non-functional (NF)-PNETs. Imaging analysis with radiomics may be able to elucidate biologic data such as tumor grade, without the need for tissue sampling. Our study aims to create an automatic pipeline from segmentation to radiomics-signature building to preoperatively predict tumor grade. Methods: Patients that underwent resection between 2003-21 with adequate preoperative arterial phase CT scans were divided into training and validation cohorts. In the training cohort, the pancreas and tumor region were manually segmented and used to train an auto-segmentation model. The validation cohort then underwent automatic segmentation. A total of 255 radiomics features were extracted from the tumor region. Correlated features were removed, and the minimum redundancy maximum relevance (mRMR) method was used to select the final feature set. These features were used to train a Support Vector Machine (SVM)-based classifier through the training cohort to predict grade, which was dichotomized into grade I versus II/III. The radiomic based prediction model was then evaluated in the automatically segmented validation cohort. Results: A total of 186 patients were identified and divided into training (n = 140) and validation (n = 46) cohorts. Median age was 57 (27, 85) and 52% were male. 113 (62%) and 70 (38%) patients were grades I and II/III, respectively. Median tumor size was 24 mm (6, 200) and 43 (26%) patients had positive nodal disease. The auto-segmentation model was able to accurately segment the tumor region in 33 (72%) patients of the validation cohort. In the training cohort (n = 140), the radiomics-signature produced an area under the curve (AUC) of 0.87 (0.81, 0.93). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 0.94 (0.9, 0.98), 0.74 (0.66, 0.81), 0.72 (0.65, 0.80) and 0.97 (0.94, 1.00) respectively. In the auto-segmented validation cohort (n = 33), the radiomics model produced an AUC of 0.75 (0.61, 0.90). Sensitivity, specificity, PPV and NPV were 0.88 (0.77, 0.99), 0.62 (0.46, 0.79), 0.71 (0.56, 0.87) and 0.83 (0.71, 0.96), respectively. Conclusions: The proposed auto-segmentation model was able to automatically identify tumor regions with a high degree of accuracy. Similarly, the subsequent radiomics-signature was also able to strongly discern PNET grade. This automatic pipeline bypasses manual segmentation and could help incorporate a radiomics-signature into preoperative clinical decision-making for PNETs.
Real-world data of durvalumab plus gemcitabine and cisplatin in patients with advanced biliary tract cancer: A Thailand multicenter observational study.
Authors: Suebpong Tanasanvimon, Kunlatida Maneenil, Kosin Wirasorn, Kijjakom Thanasombunsukh, Krittiya Korphaisarn, Chirawadee Sathitruangsak, Passakorn Wanchaijiraboon, Teerada Siripoon, Nattaya Teeyapan, Chanchai Charonpongsuntorn, Thatthan Suksombooncharoen, Tawasapon Thambamroong, Wannisa Laosuangkoon, Chavapon Ngokngarm, Pronwasun Simseekeaw, Charuwan Akewanlop, Ekaphop Sirachainan
Journal: Journal of Clinical Oncology (2025)

607 Background: Currently, durvalumab plus gemcitabine and cisplatin is a standard of care for patients with advanced biliary tract cancer (BTC). We aimed to evaluate efficacy and tolerability of durvalumab plus gemcitabine and cisplatin in real world experience in Thailand where there is high incidence of liver-fluke related cholangiocarcinoma (CCA). Methods: This is an observation study of patients with advanced BTC participating in the early access program of durvalumab since August 2023. Data were collected and analyzed for efficacy and toxicity. Results: Fifty patients participated the early access program in 14 centers across Thailand. Median follow-up time was 8.5 months. Median number of treatment cycles was 8.8 (1-16) cycles. Thirty six (72%) patients were alive and 8 (16%) patients were still on treatment. The mean age was 63 years, 60% were male and 92% were ECOG 0-1. There were 68% intrahepatic cholangiocarcinoma (CCA), 28% extrahepatic CCA and 8% gallbladder cancer. There were 29.5% objective response rate and 79.5% disease control rate. Median progression free survival (PFS) was 6.0 (95%CI 4.49-7.50) months. Eight (16%) patients were still on treatment with PFS more than 10 months. Grade 3 or 4 adverse events (AEs) were reported in 50% of patients. Most AEs were related to chemotherapy, there were 10% immune related AEs. Conclusions: In this real-world experience, durvalumab plus gemcitabine and cisplatin was efficacious and tolerable in Thai patients with advanced BTC.
Association between ctDNA levels, timing of blood collection, and overall survival in metastatic colorectal cancer.
Authors: Akinori Kobayashi, Yoshiaki Nakamura, Tadayoshi Hashimoto, Hiroya Taniguchi, Yoshito Komatsu, Taito Esaki, Yu Sunakawa, Kensei Yamaguchi, Takeshi Kato, Manabu Shiozawa, Naoki Takahashi, Takashi Ohta, Tadamichi Denda, Hironaga Satake, Tomohiro Nishina, Hisateru Yasui, Hideaki Bando, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2025)

245 Background: While circulating tumor DNA (ctDNA) detection is influenced by various factors, the impact of blood collection timing remains understudied. This study investigated the relationship between ctDNA detection, and blood collection timing and prognosis in patients with metastatic colorectal cancer (mCRC) from the GOZILA study. Methods: GOZILA is a nationwide plasma genomic profiling study using Guardant360 CDx for advanced solid tumors. This study evaluated the association of ctDNA levels with blood collection timing and prognosis in patients with mCRC. ctDNA levels were determined by the maximum variant allele frequency. Blood collection timing was categorized into five groups: naive (before initiation of 1st line treatment), after treatment initiation (days 1-14 of treatment), during treatment (between “after treatment initiation” and “before progression disease [PD]”), before PD (from 28 days before PD to PD), and after PD (after disease progression but before the next line of treatment). Overall survival (OS) was compared across treatment lines using ctDNA level cutoff of 10. Results: We analyzed 2,398 blood samples from 1,994 patients with mCRC enrolled in the GOZILA between February 2018 and July 2023. ctDNA levels were significantly lower during treatment compared to the naive (median, 13.2 vs. 5.7, p &lt; 0.001). No significant differences were observed between naive and other blood collection timing. Compared to blood collection before 1st line treatment, ctDNA levels significantly decreased before 2nd line (median, 13.5 vs. 8.3, p = 0.02) and 3rd line treatments (median, 13.5 vs. 7.6, p = 0.01). Patients with ctDNA levels&lt;10 demonstrated significantly better OS across all treatment lines, including 1st line (median, NA vs. 23.9 months, HR 0.49, 95% CI, 0.34-0.72), 2nd line (median, 22.1 vs. 10.3 months, HR 0.42, 95% CI, 0.33-0.55), and later line treatments (FTD/TPI: median, 12.7 vs. 5.7 months, HR 0.51, 95% CI, 0.26-0.99; FTD/TPI+Bev: median, 9.3 vs. 6.5 months, HR 0.55, 95% CI, 0.37-0.82; Regorafenib: median, 13.5 vs. 7.4 months, HR 0.45, 95% CI, 0.26-0.80). Conclusions: In mCRC, blood collection during treatment is suboptimal due to decreased ctDNA levels. Patients with ctDNA levels &lt;10 showed significantly better OS across all treatment lines. Optimal timing of blood collection can enhance ctDNA levels, enabling more accurate gene mutation assessment and stratifying outcomes.
LAPIS: Randomized phase 3 trial of chemotherapy (CTX) with and without pamrevlumab (PAM) for locally advanced pancreatic cancer (LAPC).
Authors: Vincent J. Picozzi, Khurum Hayat Khan, Pascal Hammel, Michele Reni, Daniel Lin, Woo Jin Lee, Roberto A. Pazo Cid, Vaibhav Sahai, Andres J Munoz Martin, Jianjun Liu, Ende Zhao, Ewa Carrier, Teresa Macarulla
Journal: Journal of Clinical Oncology (2025)

675 Background: PAM improved response, surgical eligibility, and resection rates when combined with CTX in phase 1/2 LAPC trials (NCT01181245; NCT02210559). LAPIS (NCT03941093) evaluated efficacy and safety of PAM + CTX in unresectable LAPC. Methods: LAPIS was a global, double-blind, placebo-controlled phase 3 trial of adults with treatment-naïve, -confirmed unresectable LAPC. Patients received (randomized 1:1) PAM (35 mg/kg Q2W) or placebo (PBO) plus CTX (gemcitabine + nab-paclitaxel [GnP] or FOLFIRINOX [FFX] per standard protocol) for up to six 28-day cycles. based on changes in -9, on FDG-PET, resectability, with final surgical decision made by surgeon. Primary endpoint: overall survival (OS); secondary endpoints: event-free survival (EFS), progression-free survival (PFS), and objective response rate (ORR. Safety (including treatment-emergent adverse events [TEAEs]) was evaluated in patients who received treatment. Results: 143 and 141 patients (median [range] age, 65.0 [31–90] yrs; 53.2% male) were randomized to PAM and PBO arms. 142 and 141 received treatment: GnP, 114 (79.7%) and 112 (79.4%); FFX, 28 (19.6%) and 29 (20.6%). PAM (64.8%) and 96 PBO (68.1%) patients completed 6 treatment cycles. . Survival similar for PAM and PBO arms (Table) and did not differ by. For PAM + FFX vs PBO + FFX, respiratory, thoracic and mediastinal disorders (39.3% vs 27.6%) and skin and subcutaneous tissue disorders (53.6% vs 37.9%) occurred &gt;10% more with PAM; TEAE frequencies were similar with PAM + GnP and PBO + GnP. One treatment-related death occurred in PAM arm. Conclusions: LAPIS contained important LAPC trial innovations: pre/post-CTX FDG-PET imaging, objective criteria for surgical intervention, external surgical review panel, and composite EFS measurement. Addition of PAM to CTX was not associated with additional toxicity but did not improve survival outcomes for unresectable LAPC. Clinical trial information: NCT03941093 . LAPIS endpoints. PAM arm (n=143) PBO arm (n=141) OS, months, median (95% CI) events=118 (82.5%)17.25 (15.47, 18.89) events=112 (79.4%)17.94 (14.59, 20.34) HR (95% CI)1.08 (0.83, 1.41)p=0.55 EFS, a months, median (95% CI) events=99 (69.2%)5.72 (5.59, 6.01) events=102 (72.3%)5.78 (5.62, 6.37) HR (95% CI)1.05 (0.78, 1.39) PFS, months, median (95% CI) events=48 (33.6%)9.36 (7.75, 11.79) events=44 (31.2%)9.40 (7.69, 10.84) HR (95% CI)1.01 (0.65, 1.56) ORR, n (%) 43 (30.1) 64 (45.4) OR (95% CI)0.50 (0.31, 0.82) Complete response 0 0 Partial response 43 (30.1) 64 (45.4) CI, confidence interval; HR, hazard ratio; OR, odds ratio. a Earliest of 1) failure to achieve local disease-free status at end of treatment and/or after surgery; 2) local or distant recurrence/progression; or 3) death.
A randomized phase 2 study of an individualized neoantigen-targeting immunotherapy in patients with newly diagnosed metastatic microsatellite stable colorectal cancer (MSS-CRC).
Authors: Joel R. Hecht, Alexander I. Spira, Anthony V. Nguyen, Lyudmyla Derby Berim, Alexander Starodub, Meredith Pelster, David Gallinson, Anup Kasi, Matthew Reilley, Agustin Pimentel, Ki Young Chung, Fa-Chyi Lee, Brian Chauder, Kyounghwa Bae, Desiree Schneck, Andrew R. Allen, Karin Jooss, Andrew R. Ferguson, J. Thaddeus Beck
Journal: Journal of Clinical Oncology (2025)

LBA13 Background: Neoantigen-targeting immunotherapy aims to provide therapeutic benefit to patients by generating potent neoantigen-specific T cells. GRANITE is an immunotherapy regimen that uses chimpanzee adenovirus and self-amplifying mRNA vaccines encoding patient-specific neoantigens in combination with immune checkpoint inhibitors. Preliminary efficacy was noted in MSS-CRC (Palmer et al Nature Medicine 2022) and this regimen is being assessed in a randomized Phase 2 study in 1L metastatic MSS-CRC (NCT05141721). Methods: Patients (pts) with 20 neoantigens based on the EDGEÔ prediction model were randomized 1:1 to receive the GRANITE regimen in addition to 1L standard of care (SOC) (GRANITE vaccine arm), or 1L SOC alone (control arm). Results: Baseline demographics and disease characteristics were balanced between arms. As of 15 Oct 2024, GRANITE pts had an improvement in PFS relative to control pts (HR=0.73, 90% CI [0.44, 1.21]). In this study, high and low disease burden groups were identified using baseline ctDNA assessed by Gritstone’s validated, highly sensitive, tumor-informed assay. Patients with low disease burden benefited more than those with high disease burden, consistent with emerging data suggesting neoantigen-targeting immunotherapy having greater activity in minimal disease settings (e.g., adjuvant setting). Furthermore, in the low disease burden group at the most recent study visit, more patients were free of progression with very low ctDNA levels (ie, below the limit of quantification of the assay) in the GRANITE arm, 41% (7/17), versus the control arm, 21% (3/14). The greater proportion of GRANITE patients both free of progression and with very low ctDNA, suggests potential further separation of PFS cuves with additional follow up. Neoantigen-specific T cell responses were observed in 100% of patients in the GRANITE arm with evaluable PBMC samples (17/17 assessed by ex vivo and in vitro stimulation ELISpots). Molecular responses based on a reduction in ctDNA at a single timepoint was similar between arms (39% in GRANITE and 40% in control arms). Most common (≥20%) treatment-related adverse events (TRAE) included pyrexia and influenza like illness and no pts discontinued due to a TRAE. Conclusion: This randomized study shows GRANITE may benefit patients, especially those with low burden disease, in this front line setting of metastatic MSS-CRC that has not benefitted from immunotherapy. Updated analysis will be presented. Clinical trial information: NCT05141721 .
Efficacy of immune checkpoint inhibitors in patients with advanced pancreatic NETs displaying high TMB and MMR alterations following treatment with alkylating agents.
Authors: Jonathan R. Strosberg, Anna Koumarianou, Rachel Riechelmann, Jorge Hernando, Sara Cingarlini, Joakim Crona, Taymeyah E. Al-Toubah, Leonidas Apostolidis, Emily K. Bergsland, Thorvardur Ragnar Halfdanarson, Jerome Cros, Louis De Mestier DU Bourg
Journal: Journal of Clinical Oncology (2025)

662 Background: Alkylating-based chemotherapy (ALK) is one of the main treatments used in patients with advanced pancreatic neuroendocrine tumors (PanNETs). Its use has been associated with an increased risk of grade progression and acquisition of a hypermutator phenotype, associated with frequent alterations of the mismatch repair (MMR) genes. This suggests a potential benefit of immune checkpoint inhibitors (ICI) that are otherwise ineffective in ALK-naïve PanNETs, which are mostly hypomutated. We aimed to describe the efficacy of ICI in patients with advanced PanNET pretreated with ALK. Methods: We assembled an international retrospective cohort of patients with advanced PanNET who received at least one cycle of ICI, and who had previously received at least 3 months of ALK. Patients with poorly-differentiated neuroendocrine carcinoma were excluded. The primary endpoint was progression-free survival (PFS) and the secondary endpoint was the objective response rate (ORR). The impact of tumor mutational burden (TMB, high being defined by &gt;10 mut/Mb) and MMR alterations (mutations or IHC) was explored. Results: We included 39 patients (median age 58.7, male sex 62%). All PanNETs were progressive at baseline and presented a median of 3 (IQR, 2-4) metastatic sites. Tumors were predominantly classified as G2 (47%) or G3 (42%), with a median Ki-67 of 18.5% (IQR, 12-35). 23/27 patients with tumor tissue or ctDNA NGS testing had high TMB (median, 35 mut/Mb; IQR, 24-106) and 12/22 had MMR alterations. Patients had previously received an average of 14 cycles (IQR, 7-25) of ALK (temozolomide 78%, streptozotocin 18%, dacarbazine 4%), which had yielded objective response in 72% of cases. In addition, patients had received a median of 4 (IQR, 3-5) other treatments (including platinum drugs in 80% and PRRT in 51%). ICI mainly consisted in an anti-PDL1/PD1 + anti-CTLA4 combination (85%) or a monotherapy (15%), with a median of 3 (IQR, 2-8) cycles. The ORR was 18% and the disease control rate was 46%. Median PFS was 2.8 months (95% CI, 0.62-4.96) and 6-month PFS rate was 31%. 19% of patients had grade 3-4 toxicity. Patients with high TMB had higher ORR (30% vs. 0%, p=0.03) and longer median PFS (4.9 vs. 2.1 months, p=0.004) compared with patients with low/unknown TMB. Patients with altered MMR had higher ORR (42% vs. 7%, p=0.02) and longer median PFS (8.9 vs. 2.5 months, p=0.014) compared with patients with no/unknown MMR alterations. Conclusions: While ICI shows limited efficacy in unselected patients with advanced PanNETs pretreated with ALK, it may be an effective treatment option in case of high TMB and MMR alterations.
A phase 1/2 study to evaluate CHM-2101, an autologous cadherin 17 (CDH17) chimeric antigen receptor (CAR) T cell therapy for the treatment of relapsed or refractory gastrointestinal cancers.
Authors: Jennifer Rachel Eads, Maria Pia Morelli, Daniel Olson, Jason Blair Litten, Stephanie H. Astrow, Meredith Pelster
Journal: Journal of Clinical Oncology (2025)

TPS844 Background: Patients with advanced gastrointestinal (GI) malignancies have poor prognoses and limited treatment options. Cadherin 17 (CDH17) is a cell membrane-associated protein important for GI cell-cell interactions that is expressed in proximity to epithelial tight junctions. In some GI malignancies, CDH17 expression is also expressed diffusely across the cancer cell membrane, thus providing access to CDH17 directed CAR T-cells. CHM CDH17 is a third generation autologous CAR T-cell product candidate that was designed to target and eradicate CDH17+ solid tumors. Notably, expression of CDH17 varies across indications in the cancer setting CDH17– TABLE 1. Methods: Clinical Trial NCT06055439 is a seamless Phase 1/2 clinical trial of autologous CHM CDH17 CAR T-cells for patients with advanced gastric cancer (GC), colorectal (CRC) cancer or neuroendocrine tumors (NETs) of the midgut or hindgut. As CDH17 expression in GC is heterogenous, GC subjects will be screened for CDH17 expression. In preparation for receiving CDH17 CAR T-cells, subjects receive 3-days of lymphodepleting intravenous (IV) chemotherapy (fludarabine and cyclophosphamide). The Phase 1 portion of the clinical trial uses a 3+3 dose escalation and a starting dose of 50 million CAR-T cells in a single IV infusion. Decisions regarding dose escalation/de-escalation are based on real-time dose-limiting toxicity evaluation during the first 28 days of treatment during dose escalation. After establishing a recommended Phase 2 dose, three indication-specific Simon 2-Stage cohorts will be initiated in (1) GC (2) CRC and (3) NETs of the midgut or hindgut to further characterize the safety and assess the efficacy of CHM CDH17 CAR T-cells. This is an ongoing first-in-human multi-center clinical trial of CHM CDH17, a CDH17 directed autologous CAR T-cell product candidate, enrolling subjects with advanced GI cancers that express CDH17. Clinical trial information: NCT06055439 . Expression of CDH17 in selected gastrointestinal cancer indications. Indication Sample size CDH17Expression %* Colorectal cancer 821 96% Neuroendocrine tumors of the midgut and hindgut 119 97% Gastric cancer 1,409 64% *Expression of total tumors tested for CDH17 by immunohistochemistry (CHM data on file).
Digesting danger: A two-decade study exploring the association between food processing and colon cancer.
Authors: Elise Katsnelson, William Jin
Journal: Journal of Clinical Oncology (2025)

87 Background: Dietary patterns play a significant role in cancer prevention and progression, yet the specific association of food processing with colon cancer remains largely under-investigated. The NOVA classification system categorizes foods by their level of processing, providing a unique way to examine this relationship. Colon cancer remains a leading global health concern, and emerging evidence points to diet as potential contributors. This study explores associations between NOVA-classified foods and colon cancer, offering new insights into the role of food processing in cancer development. Methods: Survey data from the NHANES database (from 1999 to 2018) was probed for demographic and clinically relevant data, and day one food journals were converted into NOVA classifications. Participants aged 20 and older were included for analysis, including those with and without colon cancer (n=339 and 47615, respectively). Independent two-sample t-tests were conducted to compare the mean proportion of daily energy consumption of various NOVA food categories between the two groups, and a Benjamini-Hochberg correction was applied to adjust for multiple comparisons at p&lt;0.05. Sensitivity analyses were performed using total grams and percent total caloric intake as inputs. Subgroup analyses were conducted via a logistic regression model including BMI, age, ethnicity, gender, education, country of birth, and military service. Results: Individuals with colon cancer had higher intake of ham and salted meats (NOVA 3, adjusted p=0.028) compared to those without cancer. Conversely, individuals without cancer consumed more legumes (NOVA 1, adjusted p=0.028), oils (NOVA 2, adjusted p=0.023), and “other processed foods” that did not fall into a specific processed food category (NOVA 3, adjusted p=0.038). Subgroups analyses revealed a greater association with colon cancer for age greater than 50 and non-hispanic White ethnicity. Conclusions: To our knowledge, this is the only study at this scale that evaluates colon cancer prevalence in the context of dietary behaviors stratified by level of industrial processing. The significant associations between ham and salted meats consumption, age greater than 50, and non-Hispanic White ethnicity with increased cancer prevalence highlight the impact of dietary and demographic patterns on colorectal carcinogenesis. Additional studies are needed to confirm these hypotheses in the prospective setting.