tbuckley/cabot-search huggingface dataset:
Survival benefits of adjuvant chemotherapy after surgical resection of para-aortic lymph node metastasis from colorectal cancer: A multicenter retrospective study.
Authors: Hiroaki Nozawa, Sono Ito, Koji Murono, Kazuhito Sasaki, Shigenobu Emoto, Yuichiro Yokoyama, Shinichi Yamauchi, Yusuke Kinugasa, Yoichi Ajioka, Soichiro Ishihara
Journal: Journal of Clinical Oncology (2025)

140 Background: Surgical removal of metastasized paraaortic lymph nodes (PALNs) can prolong the survival of certain patients with colorectal cancer (CRC). However, the role of postoperative chemotherapy in such patients remains unknown. Methods: This multi-center retrospective study examined97 patients with PALN metastasis from CRC who underwent surgical resection at 36 centers in Japan between 2010 and 2015. Based on adjuvant chemotherapy (AC) after the lymphadenectomy, the patients were classified into Non-AC and AC groups (27 and 70 patients, respectively). After the exclusion of patients receiving irinotecan, the latter group was further categorized into 5-fluorouracil (5-FU) and oxaliplatin (L-OHP) subgroups (14 and 52 patients, respectively) according to the use of L-OHP. Background characteristics and postoperative survival were compared among the groups. Results: Marked differences were not seen in background characteristics, except for neoadjuvant treatment, between the Non-AC and AC groups. The AC group exhibited better recurrence-free survival (RFS, p = 0.009) and overall survival (OS, p = 0.040) than the Non-AC group. However, RFS and OS of the 5-FU group did not differ from those of the L-OHP group (p = 0.73 and p = 0.92, respectively). Conclusions: AC contributed to the improved prognosis of patients after the removal of PALN metastasis from CRC, but L-OHP did not offer additional survival benefits. Prospective studies comparing Non-AC with 5-FU- and L-OHP-based AC are needed to confirm these findings.
Optical coherence tomography and elastography for the visualization of architecture and stiffness differences in gastric cancer and dysplasia.
Authors: Alana Gonzales, Caitlin Ruhland, Ryan Mitstifer, Photini Rice, Travis Sawyer, Jennifer Barton
Journal: Journal of Clinical Oncology (2025)

382 Background: Individuals at high risk for gastric cancer may be recommended to undergo risk-reducing gastrectomy, which leads to life-long morbidity. Surveillance with endoscopy can be an appropriate and effective option for avoiding unnecessary surgery. Gastric cancer is commonly characterized by changes in tissue architecture and increased tissue stiffness, but visualization of these alterations is challenging for white light endoscopy methods. We utilized optical coherence tomography (OCT), a non-destructive imaging modality that uses reflected near-infrared light to generate cross-sectional images of tissue, to visualize microstructure and relative tissue stiffness. Methods: We utilized two modes of OCT for visualization of ex vivo tissue samples collected from patients undergoing gastrectomy for gastric cancer, endoscopic mucosal resection, or endoscopic biopsy. Images were collected with a benchtop OCT system (Thorlabs Telesto TEL221). Structural OCT was used to visualize changes in tissue architecture including thickened mucosa and irregular put structure of the mucosa. Optical coherence elastography (OCE) was used to extract relative measures of tissue stiffness using an optical palpation method. A phantom of known mechanical properties was placed on the tissue and an axial force was applied. The resulting deformation (strain) of the phantom provided relative measurements of tissue stiffness. Classification of normal and cancerous tissue was confirmed by histology. Results: Structural OCT imaged architectural features of tissue with high resolution (&lt;10 um) and depth of imaging up to 1.5 mm. Strain maps generated with OCE data showed that normal gastric tissue had relatively consistent stiffness, whereas stomach cancer and dysplasia exhibited increased tissue stiffness compared to normal. Conclusions: Structural OCT and OCE captured changes in tissue architecture and increased stiffness in patient samples of gastric cancer and dysplasia. These tissue features are classic characteristics of cancer, making this technique a useful screening tool for several cancer types. Future work aims to implement endoscopic OCT and OCE to detect cancer at early stages in vivo .
Immunotherapy engagement in pancreatic adenocarcinoma: Provisional results of iLSTA study— Durvalumab, LSTA1 (certepetide), gemcitabine, and nab-paclitaxel for locally advanced pancreatic ductal adenocarcinoma.
Authors: Andrew Peter Dean, Mikael Johansson, Ian Yusoff, Samarth Rao, Susan Sparrow, Priyanthi Kumarasinghe, Suresh Navadgi, Yuki Watanabe, Laurence Webber, Jenny Grew, Shane Fitzgerald, Olivia Rose Comito
Journal: Journal of Clinical Oncology (2025)

746 Background: Pancreatic ductal adenocarcinoma (PDAC) is characterised by a dense, extracellular matrix-rich stroma, which creates a physical barrier against drug penetration. Evidence suggests that the iRGD peptide, LSTA-1, can increase the penetration of anti-cancer drugs to tumours through selective targeting of tumour endothelial cell receptors. Additionally, LSTA-1 administration promotes CD8+ immune cell tumour infiltration, potentially enabling immunotherapy as a treatment modality. iLSTA examined safety, tolerability and effect of the combination. Methods: Participants diagnosed with locally advanced PDAC were divided into 3 cohorts in a 1:1:4 ratio. Cohort 1 (n=5) received gemcitabine (1000mg/m 2 ), nab-paclitaxel (125mg/m 2 ), placebo LSTA-1 (3.2mg/kg) and placebo durvalumab (750mg). Cohort 2 (n=5) received gemcitabine, nab-paclitaxel, active and placebo LSTA-1, and placebo durvalumab. Cohort 3 (n=20) received gemcitabine, nab-paclitaxel, LSTA-1 and durvalumab. Tissue biopsies via endoscopic ultrasound were obtained pre-treatment and between weeks 12 and 16 for analysis of tumour infiltrating lymphocytes (TILs). Patient tumour sizes were assessed every 8 weeks using radiological imaging according to RECIST v1.1, and serum CA19-9 levels were analysed monthly. Results: 6/17 patients showed significant RECIST partial response after 2 cycles of treatment (5 patients in cohort 3), with the remaining 11 patients exhibiting stable disease. After 4 cycles of treatment, 10/17 patients demonstrated partial response (9 patients in cohort 3). Of the remaining 7 patients, 6 demonstrated stable disease, and 1 patient (cohort 2) exhibited a RECIST complete response. 13/17 patients who completed 4 treatment cycles showed a decrease in CA19-9 levels. 6 patients demonstrated &gt;90% reduction in CA19-9 (5 in cohort 3), with the remaining 7 patients showing a &gt;50% reduction in CA19-9 levels (5 in cohort 3). 12 patients underwent repeat biopsies 12-16 weeks post-treatment to assess TILs. 10 patients showed immune cell infiltration (5% to 50% stroma infiltration), 2 had no tumour found (Cohort 3). The combination was safe with no unexpected toxicities. Conclusions: The preliminary results of this study suggest that the combination of gemcitabine and nab-paclitaxel with LSTA-1 and durvalumab is safe and potentially induces tumour infiltrating lymphocytes and RECIST response in locally advanced pancreatic adenocarcinomas. Clinical trial information: ACTRN12623000223639 .
GOBLET study: Results of the safety run-in for first-line metastatic pancreatic ductal adenocarcinoma (PDAC) patients treated with pelareorep + modified FOLFIRINOX +/- atezolizumab.
Authors: Thomas Seufferlein, Dirk Arnold, Nina Burkhart, Anke C. Reinacher-Schick, Guy Ungerechts, Uwe Marc Martens, Jack Chater, Eray Goekkurt, Matt Coffey, Ruimei Li, Thomas Charles Heineman
Journal: Journal of Clinical Oncology (2025)

730 Background: Immunotherapies are effective in only the small subset of metastatic PDAC patients with MSI-H or dMMR tumors. Pelareorep (pela) is a non-genetically modified, intravenously administered reovirus that selectively infects cancer cells. It stimulates the expansion of pre-existing tumor-infiltrating lymphocyte (TIL) clones, and it makes tumors visible to the immune system by upregulating interferon-induced gene expression including PD-L1, CXCL9, CXCL10, and CXCL11. PD-L1 upregulation also provides a basis for potential synergy between pela and immune checkpoint inhibitors. Pela combined with gemcitabine/nab-paclitaxel/atezolizumab showed promising tumor responses in mPDAC. Here, we are assessing the safety and preliminary efficacy of pela + mFOLFIRINOX +/- atezolizumab in a new cohort in the ongoing GOBLET study. Methods: GOBLET is a phase 1/2, open-label, Simon two-stage study in patients with advanced or metastatic GI cancers. In this new GOBLET cohort (Cohort 5), patients with newly diagnosed mPDAC are randomized to receive either pela + mFOLFIRINOX or pela + mFOLFIRINOX + atezolizumab. The primary endpoints are safety and objective response rate (ORR). In Stage 1, 15 evaluable patients will be enrolled in each arm. Both arms include a 3-6 patient safety run-in that must be successfully completed prior to opening the study to full enrollment. If pre-specified ORR success criteria are met, one or both arms may be advanced to Stage 2 during which 17 additional evaluable patients/per arm will be enrolled. Results: The 3-patient safety run-in for both arms of Cohorts 5 (6 patients total) have been enrolled, and all patients have completed the required 1-month evaluation period. Cohort 5 safety data have been reviewed by the independent Data Safety Monitoring Board (DSMB). The DSMB identified no safety signals attributable to the combination of pela and mFOLFIRINOX +/- atezolizumab and recommended that enrollment into these arms of Cohort 5 continue without modification. Reported adverse events are consistent with the known toxicities of the components of the treatment regimen. Tumor response results are pending. Conclusions: The results of the GOBLET Cohort 5 safety run-in indicate that pela can be given safely in combination with mFOLFIRINOX +/- atezolizumab to newly diagnosed mPDAC patients. Safety and efficacy of these combination therapies will continue to be monitored (Eudra-CT: 2020-003996-16). Clinical trial information: 2020-003996-16 .
Total neoadjuvant therapy with FOLFOX plus bevacizumab and short-course radiotherapy for Ras mutant, high-risk, locally advanced rectal cancer: The TRAINER trial.
Authors: Bo Feng, Jingyi Liu, Tao Ma, Zhenghao Cai, Sen Zhang, Xiao Yang, Haiqin Song, Gang Cai, Ximo Xu, Hao Zhong, Mengqin Yu, Naijipu Abuduaini, Lixuan Jiang, Xiaohan Wang, Wanyu Wang
Journal: Journal of Clinical Oncology (2025)

133 Background: Total neoadjuvant therapy (TNT) intensified by the combination of targeted therapy or immunotherapy is warranted to achieve satisfying local and systemic control for high-risk locally advanced rectal cancer (LARC). Our study aimed to explore the efficacy and safety of a FOLFOX-based TNT regimen plus bevacizumab and short-course radiotherapy (SCRT) in Ras-mutant high-risk LARC patients. Methods: In this single-arm, single-center, phase II trial, LARC patients with at least one risk factor (cT3c-4, mesorectal fascia positive, cN2, lateral lymph node involvement, and extramural venous invasion positive) were recruited and only Ras-mutant patients were included. Four cycles of FOLFOX plus bevacizumab were arranged as induction chemotherapy followed by SCRT (25Gy/5Fx) and two cycles of FOLFOX as consolidation chemotherapy. Surgery was performed 8 weeks after completion of radiotherapy. After surgery, high-risk stage III patients (T4 or N2) were recommended to receive an extra 6 cycles of FOLFOX as adjuvant chemotherapy, while low-risk stage III patients were scheduled for regular follow-up. Patients with clinical complete response(cCR) were allowed to choose the “Watch &amp; Wait” (W&amp;W) strategy instead of surgery. The primary endpoint was the complete response (CR) rate, defined as the total rate of cCR plus pathological complete response (pCR). Secondary endpoints included adverse events of TNT, postoperative complications, 2-year disease-free survival, and overall survival. Results: Between April 2, 2021, and March 12, 2024, 47 of 51 enrolled patients were eligible for treatment. All patients completed the prescribed TNT cycles, and six (12.8%) of them had dose reduction. The CR was achieved in 18 (38.3%) patients, including 14 (29.8%) pCR. No grade IV-V toxicity was observed and the incidence of grade III toxicities was 34.0%. Four patients (8.5%) achieved cCR and chose the W&amp;W strategy. The other 43 patients underwent curative surgery and anal preservation was achieved in 39 (90.7%) patients. Seven patients (16.3%) experienced postoperative complications, including four (9.3%) cases of anastomotic leakage. Conclusions: The intensified TNT regimen combined with bevacizumab achieved a satisfying CR rate with acceptable toxicities and complications for Ras-mutant high-risk LARC patients. Long-term survival data of this cohort are needed to validate the efficacy of this regimen further. Clinical trial information: NCT04923620 .
Comprehensive analysis of socioeconomic and clinical factors contributing to treatment delay in early-onset colorectal cancer.
Authors: Manasawee Tanariyakul, Jared David Acoba
Journal: Journal of Clinical Oncology (2025)

32 Background: The prevalence of early-onset colorectal cancers (EOCRC) is rising globally. Disparities in social determinants of health can delay access to treatment and impacting outcomes. This study aims to analyze factors influencing time from diagnosis to treatment among EOCRC patients in a racially diverse population, considering tumor factors and sociodemographics. Methods: We analyzed EOCRC data from patients diagnosed between 2000 and 2022 at Queen’s Medical Center in Honolulu, Hawaii. Time from diagnosis to treatment for Asians, Whites, and Native Hawaiian or Other Pacific Islanders (NHOPI) was assessed using the Kaplan-Meier Method. Cox proportional hazards regression models were used to identify predictors, adjusting for clinical and pathological factors. Results: A total of 379 patients were analyzed. NHOPI were more like to be underinsured compared to Whites and Asians. In the unadjusted Cox model, underinsured/uninsured status, older age, unknown stage, left sided, and rectal locations were associated with delayed treatment. After adjustment, underinsured/uninsured status, older age, and rectal location remained significant predictors of delayed treatment. Conclusions: EOCRC patients with underinsured/uninsured status, age, and rectal tumor location are significantly associated with delayed in cancer treatment. While age was statistically significant, its clinical impact appears minimal. The need for a multidisplinary approach and additional preoperative staging in rectal cancer may explain treatment delays even after adjustment. Improving treatment accessibility and reducing delays, especially for underinsured EOCRC patients, is important. Univariate and multivariate analysis of time from diagnosis to treatment. Univariate Multivariate HR (95% CI) p-value HR (95% CI) p-value Insurance - - - - Private insurance - - - - Underinsured/Uninsured 0.692 (0.545-0.878) 0.003 0.706 (0.55-0.906) 0.006 Race White - - - - Asian 0.912 (0.696-1.195) 0.503 0.817 (0.619-1.077) 0.151 NHOPI 0.749 (0.548-1.025) 0.071 0.779 (0.562-1.08) 0.134 Age 0.978 (0.96-0.997) 0.021 0.968 (0.949-0.987) 0.001 Histopathology grade Grade 1&amp;2 - - - - Grade 3&amp;4 1.046 (0.798-1.371) 0.746 1.083 (0.813-1.441) 0.587 Stage 1 - - - - 2 1.022 (0.718-1.456) 0.902 1.071 (0.744-1.539) 0.713 3 1.227 (0.896-1.682) 0.203 1.387 (0.997-1.931) 0.052 4 0.964 (0.673-1.381) 0.842 1.039 (0.716-1.507) 0.842 Unknown 0.631 (0.406-0.981) 0.041 0.748 (0.473-1.182) 0.213 Sex Male - - - - Female 1.029 (0.836-1.267) 0.785 1.072 (0.868-1.325) 0.518 Microsatellite status Stable - - Unstable 1.074 (0.616-1.875) 0.8 Not done/Unknown 1.259 (1.004-1.577) 0.046 Location of Tumors Right - - - - Left 0.631 (0.468-0.851) 0.003 0.735 (0.535-1.011) 0.058 Rectal 0.43 (0.317-0.582) &lt;0.001 0.448 (0.327-0.613) &lt;0.001 NHOPI: Native Hawaiians and Other Pacific Islanders. HR: Hazard Ratio CI: Confidence Interval.
Predictive factors for the efficacy of nal-IRI + 5FU/LV therapy in patients previously treated with conventional irinotecan.
Authors: Yasutsugu Asai, Satoshi Kobayashi, Kazumasa Shiraishi, Masato Enomoto, Tomomi Hamaguchi, Yuichiro Tozuka, Taito Fukushima, Shun Tezuka, Makoto Ueno, Junji Furuse
Journal: Journal of Clinical Oncology (2025)

737 Background: There were some reports that nal-IRI + 5FU/LV (NAPOLI) therapy was effective for patients with unresectable pancreatic cancer who had a history of treatment containing conventional irinotecan (IRI) though the others did not. We aimed to investigate the factors that contribute to the effectiveness of NAPOLI therapy for patients who have already received IRI-containing treatment. Methods: We retrospectively enrolled the consecutive patients who had previously treated with IRI-containing treatment and started NAPOLI therapy at our hospital between June 2020 and December 2022. We compared the patient backgrounds of patients who achieved CR, PR, or SD according to RECISTv1.1 (effective group) and those who did not (ineffective group). Continuous variables were divided into two groups by the median of the entire population, and factors contributing to the effectiveness of NAPOLI therapy were determined by logistic regression analysis. Results: The subjective were 52 patients. The reason for discontinuation of IRI-containing treatment was refractory and intolerant in 45 and 7 patients, respectively. The median age was 65 years. Twenty-three patients (44%) had ECOG PS of 0, and 41 patients (79%) had metastatic disease. The median albumin, CRP, CEA and CA 19-9 was 3.8 g/dL, 0.3 mg/dL, 8.5 ng/mL and 2082 U/mL, respectively. Twenty-one patients (40%) showed SD and they were allocated in the effective group whereas 31 patients were in the ineffective group. Of the 21 patients in the Effective Group, 16 patients(76%) were refractory, while of the 31 patients in the Ineffective Group, 29 patients (94%) were refractory. The factors contributing to disease control were PS of 0 (odds ratio, 5.79; 95% confidence interval, 1.34–25.0), CA 19-9 &lt;1000 U/mL (odds ratio, 5.53; 95% confidence interval, 1.26–24.3), and Alb &gt;3.8 g/dL (odds ratio, 5.19; 95% confidence interval, 1.14–23.7). Age, sex, disease stage, serum level of CRP, and CEA did not affect the effectiveness of NAPOLI therapy. Conclusions: Even in patients who have already received IRI treatment, the NAPOLI regimen is expected to be effective in patients with PS of 0, Alb &gt;3.8 g/dL, and CA 19-9 &lt;1000 U/mL.
Effect of ketorolac on serum GDF-15 and IL-8 in patients with pancreatic cancer with cachexia.
Authors: Abrahm Levi, Matthew Ebia, Talya Geller, Keith Jorgensen, Lingbing Zhang, Arsen Osipov, Jun Gong, Andrew Eugene Hendifar
Journal: Journal of Clinical Oncology (2025)

713 Background: Cancer cachexia deteriorates the quality of life, chemotherapy tolerance and survivability of pancreatic cancer (PC) patients. Although a prevalent condition affecting PC patients, there are no approved therapies for cachexia and its mechanism of action is poorly understood. Elevated growth differentiation factor 15 (GDF-15), a stress-induced cytokine, has been associated with the pathogenesis of cachexia. Similarly, prior studies have displayed positive correlations between the proinflammatory factor interleukin-8 (IL-8) and PC cachexia. This abstract focuses on the exploratory endpoints (serum GDF-15 and IL-8 levels) of a feasibility trial on ketorolac as a treatment for PC cachexia. Methods: Patients took ketorolac 10 mg PO QID for 5 consecutive days, with weights measured on Day 1 (D1) and Day 6 (D6). Serum cytokines were drawn on D1 and D6. IL-8 was measured using a HDF15 assay (Eve Technologies). GDF-15 was measured using a human R-plex GDF-15 assay. Activity (e.g., number of steps) was measured via Fitbit. Differences in weight, activity, GDF-15, and IL-8 were analyzed using two-sample paired t-tests. Results: Twenty-nine patients were enrolled, of which 19 were evaluable. Median age was 70, 47.4% (9/19) were female, and 94.7% (18/19) were adherent with ketorolac. Statistically significant increases in both weight per baseline BMI and activity were observed from D1 to D6 (0.0716±0.1079 kg/BMI, p=0.012; 1423±2477 steps, p=0.0221). Of the 19 evaluable patients, 16 patients provided complete D1 and D6 pairs of serum cytokines. From D1 to D6, the mean GDF-15 level decreased by 277.5 pg/mL (p=0.529) and mean IL-8 decreased by 65.13 pg/mL (p=0.103). In all patients who gained weight (n=14), a trend toward reduced IL-8 from D1 to D6 was observed (79.57±39.57 pg/mL, p=0.065). Similarly, for patients who gained ≥ 1-kg from D1 to D6 (n=10), a trend toward reduced GDF-15 was observed (951.2±482.3 pg/mL, p=0.080). Patients with increased activity from D1 to D6 (n=12) had mean reductions of 157.7 pg/mL (p=0.643) and 70.17 pg/mL (p=0.179) in GDF-15 and IL-8, respectively. Conclusions: Given the growing literature suggesting associations between inflammatory cytokines and cancer cachexia, it is critical to investigate treatments that may possibly alter cytokine levels. Although our findings suggest that ketorolac aids in weight gain and increased activity, larger sample sizes are needed to determine whether these differences are related to reductions of specific serum cytokines. However, given reductions that trended towards significance for both GDF-15 and IL-8 serum levels within subsets of patients that gained weight on ketorolac, further studies investigating these cytokines are warranted to hopefully provide insight on the mechanistic action of ketorolac in cachexia. Clinical trial information: NCT05336266 .