tbuckley/cabot-search huggingface dataset:
Prognostic impact of postoperative complications after neoadjuvant therapy followed by esophagectomy for esophageal cancer: An exploratory analysis of phase III trial JCOG1109.
Authors: Eisuke Booka, Ken Kato, Yoshinori Ito, Hiroyuki Daiko, Kazuo Koyanagi, Miho Yamamoto, Takashi Ogata, Takashi Fukuda, Takeo Fujita, Tetsuya Abe, Masanobu Takahashi, Masayuki Watanabe, Hiroshi Ichikawa, Jun Hihara, Mitsuro Kanda, Yoichi Hamai, Takahiro Tsushima, Ryunosuke Machida, Keita Sasaki, Hiroya Takeuchi
Journal: Journal of Clinical Oncology (2025)

356 Background: We previously reported that postoperative complications after esophagectomy were significantly associated with poor long-term prognosis in the prospective randomized trial JCOG9907 (Ann Surg, 2017). JCOG1109 evaluated the efficacy and safety of neoadjuvant docetaxel plus cisplatin plus 5-FU (DCF), radiation with cisplatin plus 5-fluorouracil (CF-RT) compared with cisplatin plus 5-fluorouracil (CF) for locally advanced esophageal squamous cell carcinoma, and demonstrated the superiority of DCF compared with CF in improving overall survival (OS). In this exploratory analysis, we investigated the association between postoperative complications and prognosis in JCOG1109, where more intensive preoperative therapies and thoracoscopic esophagectomy (TE) were introduced. Methods: Patients with potentially resectable advanced thoracic esophageal cancer were randomly assigned to CF, DCF, or CF-RT therapies and followed by open esophagectomy (OE) or TE with regional lymphadenectomy in JCOG1109. The impacts of postoperative complications (≥ Grade 2) on long-term prognosis including OS and progression-free survival (PFS) were investigated in each of the three preoperative therapies. Results: Between December 2012 and July 2018, 601 patients were randomized (CF/DCF/CF-RT; 199/202/200). Of 589 eligible patients, 541 patients underwent esophagectomy (183/181/177). Any postoperative complications, pneumonia, anastomotic leakage, recurrent laryngeal nerve paralysis, or infectious complications had no significant impact on OS in each of the three arms. When divided into OE or TE, the impact of any postoperative complications on OS was attenuated by introducing TE in each of three arms; from neoadjuvant CF followed by OE group [hazard ratio (HR) 1.557, 95% confidence interval (CI) 0.881-2.752] to TE group [HR 0.802, 95% CI 0.424-1.515], from neoadjuvant DCF followed by OE group [HR 1.151, 95% CI 0.575-2.306] to TE group [HR 0.703, 95% CI 0.3363-1.471], and from neoadjuvant CF-RT followed by OE group [HR 1.548, 95% CI 0.840-2.852] to TE group [HR 1.186, 95% CI 0.627-2.245]. Conclusions: JCOG1109 showed no association between postoperative complications and long-term prognosis. The prognostic impact of postoperative complications might be attenuated by the introduction of minimally invasive esophagectomy (open to thoracoscopy) even after more intensified preoperative therapy (CF to DCF or CF to CF-RT). Clinical trial information: CRB3180009.
Impact of prior nivolumab use on the efficacy of second-line taxane-based chemotherapy in advanced gastric or esophagogastric junction adenocarcinoma.
Authors: Momoko Sano, Toshiharu Hirose, Shotaro Yamaguchi, Hidekazu Hirano, Natsuko Tsuda Okita, Hirokazu Shoji, Atsuo Takashima, Ken Kato
Journal: Journal of Clinical Oncology (2025)

352 Background: Taxane-based chemotherapy remains the standard second-line treatment after first-line treatment including anti-PD-1 antibody therapy for patients with advanced gastric or esophagogastric junction adenocarcinoma (GA/EGA). The CheckMate 649 trial suggested that prior use of nivolumab in the first-line setting was associated with longer progression-free survival (PFS) with subsequent treatment. However, there have been few reports on the difference in efficacy of taxane-based chemotherapy as second-line treatment with or without prior nivolumab use in the real-world setting. Methods: We retrospectively reviewed the medical records of patients with advanced GA/EGA who received solvent-based paclitaxel or nanoparticle albumin–bound (nab)-paclitaxel chemotherapy regimens as second-line treatment after first-line platinum-based chemotherapy between January 2018 and August 2024. We divided the patients into two groups: those who received nivolumab with the first-line chemotherapy (Nivo group) and those who did not (non-Nivo group). PFS and overall survival (OS) were estimated using the Kaplan–Meier method and compared between the two groups using the log-rank test. Hazard ratios (HRs) and 95% confidence intervals (95%CIs) were estimated by univariate and multivariate Cox regression analysis. Results: A total of 115 patients were included: 27 patients in the Nivo group and 88 in the non-Nivo group. Patient backgrounds did not differ significantly in terms of age (median 67/67 years), sex (male 59%/57%), performance status (PS; ≥2 11%/15%), site of primary tumor (EGA 11%/9%), number of metastatic sites (≥3 33%/18%), and ramucirumab use (yes 82%/82%). For the taxane regimens, nab-paclitaxel-based treatment was significantly more common in the non-Nivo group (11.1% /55.7%, p&lt;0.001). There was a tendency toward longer PFS in the Nivo group compared with the non-Nivo group (median 4.2 months [95%CI 2.8-6.0] vs. 2.3 months [95%CI 2.0-3.0], HR 0.65 [95%CI 0.40-1.03]; p=0.067.) The objective response rate was numerically higher in the Nivo group compared with the non-Nivo group (29.4% vs. 17.6%, p=0.315). OS was not significantly different between the Nivo and non-Nivo groups (median 9.6 months [95%CI 4.9-NA] vs. 6.6 months [95%CI 5.5-10.8], HR 0.92 [95%CI 0.52-1.64]; p=0.785). In the non-Nivo group, 64 patients (73%) received subsequent chemotherapy, and 63 patients (72%) received nivolumab. Multivariate analysis identified prior use of nivolumab was a favorable prognostic factor for PFS (HR 0.55 [95%CI 0.31-0.97]; p=0.039). However, prior use of nivolumab did not show a significant benefit for OS (HR 1.09 [95% CI: 0.56-2.13]; p = 0.802). Conclusions: Prior use of nivolumab in first-line platinum-based chemotherapy had a positive impact on PFS with taxane-based second-line chemotherapy in advanced GA/EGA.
Serial monitoring of circulating tumor DNA as a marker of response to immune checkpoint blockade in MSI-H gastrointestinal tumors.
Authors: Victoria Higbie, Michael Brian LaPelusa, Preksha Shah, Merrida Childress, Amaya Gasco, Amy An, Alisha Heather Bent, Bryan K. Kee, Scott Kopetz, Phat Le, Van K. Morris, Shubham Pant, Christine Parseghian, John Paul Y.C. Shen, Robert A. Wolff, Michael J. Overman
Journal: Journal of Clinical Oncology (2025)

273 Background: Microsatellite instability- high (MSI-H) tumors have high rates of response to immune checkpoint blockade (ICB) with prolonged durability of response. However, predicting who will have a response is difficult and there are limitations to radiographic evaluation of response. As circulating tumor DNA (ctDNA) offers a noninvasive approach to monitoring response and therapeutic efficacy, we sought to correlate ctDNA change with response to ICB in MSI-H gastrointestinal (GI) tumors. Methods: We conducted a retrospective study of MSI-H GI patients receiving ICB who underwent serial ctDNA sequencing. Tissue-informed ctDNA monitoring utilized comprehensive genomic profiling results of pre-treatment tumor tissue from a clinical trial assay based on FoundationOne CDx, a variant selection algorithm to exclude non-tumor variants, and multiplex PCR of up to 16 patient-specific variants to detect and quantify ctDNA. ctDNA changes were correlated with radiographic response. Results: A total of 20 patients with MSI-H tumors were evaluated including 17 colon, 2 small bowel, and 1 pancreatic. For 12 patients, it was the first exposure to ICB whereas 8 had previously progressed and were being rechallenged with ICB. Response was seen in 9 patients with a best overall response (BOR) of complete response (CR) in 4 and partial response (PR) in 5 while 5 showed stable disease (SD) and progression (PD) in 6. All patients had baseline ctDNA samples and at least 1 serial ctDNA after ICB initiation (median number of samples was 3). The mean time from baseline to first on-treatment sample was 30 days (range 13-64 days). 4 patients had undetectable ctDNA levels at baseline and remained undetectable on treatment. Of the 16 that had detectable ctDNA at baseline, 11 had a decrease in ctDNA levels at 1st on-treatment sample and 5 had an increase. The mean percent change of ctDNA at 1st on-treatment for those who had a response (CR + PR) was a 76% decrease while the mean percent change for those with SD was a 7% increase and for those with PD a 72% increase (p=0.05). Of the 6 patients with BOR of PD, 5 had an increase in ctDNA and 1 had undetectable levels at baseline. Of the 5 patients with BOR of SD, 2 had a decrease, 1 had an increase, and 2 were undetectable at baseline. Duration of SD did not correlate with initial ctDNA response. Conclusions: Early ctDNA change correlated with response in MSI-H GI tumors suggesting that serial ctDNA monitoring may provide early indication of response even prior to radiographic evaluation.
Meta-analysis of phase II/III randomized controlled trials (RCTs) to evaluate the incidence of hand-foot skin reaction (HFSR) or palmar-plantar erythrodysesthesia (PPE) syndrome in patients with gastrointestinal (GI) cancers treated with fruquintinib.
Authors: Rishi Kumar Nanda, Hazem Aboaid, Daniel Thomas Jones, Kevin Nguyen, Ramaditya Srinivasmurthy, Jason Ta, Kyaw Zin Thein
Journal: Journal of Clinical Oncology (2025)

117 Background: Fruquintinib is a selective inhibitor of vascular endothelial growth factor receptors 1, 2, and 3 blocks the angiogenesis associated with tumor proliferation. Recently, the US FDA approved fruquintinib as a third-line treatment for metastatic colorectal cancer (mCRC). As with any other novel cancer therapies, adverse events are always a concern and all patients should be monitored in order to early detect and appropriately treat any adverse events. This meta-analysis aims to assess the risk of HFSR or PPE syndrome in patients with GI cancers treated with fruquintinib. Methods: We conducted a comprehensive literature search using MEDLINE, EMBASE, and COCHRANE databases from inception through August 12th, 2024. Phase II/III RCTs utilizing fruquintinib in GI cancers mentioning HFSR or PPE as an adverse effect were included. Mantel-Haenszel method was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Heterogeneity was assessed with Cochran’s Q-statistic. Random effects model was applied. Results: A total of 1872 patients, of whom 1131 (60%) received fruquintinib, from 3 phase III RCTs (FRESCO, FRESCO-2, FRUTIGA) and 1 phase II RCT were eligible for evaluation of HFSR or PPE incidence. FRESCO, FRESCO-2, and phase II trials involved patients with mCRC, they compared fruquintinib vs placebo. FRUTIGA trial involved patients with gastric or gastroesophageal junction adenocarcinoma, it compared fruquintinib + paclitaxel vs placebo + paclitaxel. The incidence of any-grade and high-grade HFSR or PPE was higher in the fruquintinib group compared to the placebo group, 27.93% vs 3.64% (RR, 7.64; 95% CI: 4.08-14.33; P&lt;0.00001), and 8.5% vs 0% (RR, 26.0; 95% CI: 6.42-105.29; P&lt;0.00001), respectively. In the mCRC subgroup analysis, the higher incidence of any-grade and high-grade HFSR or PPE in the fruquintinib arm was also statistically significant, 29.70% vs 2.55% (RR, 10.27; 95% CI: 5.59-18.88; P&lt;0.00001), and 8.45% vs 0% (RR, 19.34; 95% CI: 3.84-97.36; P=0.0003), respectively. Conclusions: This meta-analysis revealed increased incidence of any-grade and high-grade HFSR or PPE in patients with GI cancers including mCRC treated with fruquintinib. In the FRESCO trial, this association was also shown to confer survival benefit in Chinese patients with mCRC. Prompt identification and providing proper supportive care is crucial in managing this adverse event and ultimately, preserving the patients’ quality of life.
Effects of the delay of surgery in localized rectal cancer.
Authors: Thiago do Amaral Miranda, Clara Braga dos Santos Azevedo, Eronides Salustiano Batalha Filho, Rafael Gadia, Alexandre Gheller, Fabiola Alves, Daniel da Motta Girardi, Allan Andresson Lima Pereira
Journal: Journal of Clinical Oncology (2025)

63 Background: The treatment landscape for localized rectal cancer has evolved significantly in recent years, with long-course neoadjuvant chemoradiation (CRT) and total neoadjuvant therapy (TNT) emerging as the primary options. However, the optimal timing of surgery remains an important clinical question, particularly in resource-limited settings where surgical delays can occur. Data from previous studies have shown conflicting results. This retrospective study aimed to assess the impact of delaying surgery beyond the longer interval used in previous studies, focusing on its effects on Pathologic Complete Response (pCR), DFS, and OS. Methods: We conducted a retrospective cohort study using electronic medical records from three centers in Brazil between the years 2013-2024. The study included 236 patients with localized rectal cancer treated with neoadjuvant CRT and/or chemotherapy. Patients were divided into two pre-specified groups based on the interval between the end of neoadjuvant therapy and surgery: ≤11 weeks and &gt;11 weeks. The primary endpoint was DFS. Secondary endpoints were pCR rates, and OS. Descriptive statistics were used for population analysis, while the Kaplan-Meier method estimated DFS and OS, with comparisons made using the log-rank test. A Cox proportional-hazards model was used to estimate hazard ratios and 95% confidence intervals. Results: The median age of the study population was 62 years, with males comprising 56.4% of the sample. The majority of the sample consisted of stage III patients, making up 72.2%, followed by stage II patients at 25.8%, and stage I patients at 1.9%. Most patients (77.8%) had surgery more than 11 weeks after completing neoadjuvant therapy, with a median time to surgery of 16 weeks. The pCR rates did not significantly differ between the two groups (29% for ≤11 weeks vs. 21.5% for &gt;11 weeks; p = 0.271). After a median follow-up of 30 months, the median DFS was not reached, and there was no significant difference between the groups (HR: 0.86; 95% CI: 0.48-1.5; p = 0.63). Similarly, the median OS was not reached, and no difference was observed between the groups (HR: 0.85; 95% CI: 0.47-1.54; p = 0.88). Conclusions: Delaying surgery beyond 11 weeks did not result in greater tumor downstaging in patients with localized rectal cancer. Furthermore, DFS and OS were not significantly impacted by extended intervals between neoadjuvant therapy and surgery.
Postoperative exercise in gastric cancer patients undergoing gastrectomy: A randomized controlled trial.
Authors: Hyoung-Il Kim, Tae Ho Lee, Justin Y. Jeon
Journal: Journal of Clinical Oncology (2025)

358 Background: Faster physical recovery after gastrectomy may lead to better physical and psychological health in patients with gastric cancer. Post-surgical exercise may prevent physical dysfunction and improve recovery, but its effects on physical function are not fully explored. Methods: In this trial, 52 gastric cancer patients (Stage 1-3) were randomly assigned to early postoperative exercise rehabilitation or usual care (1:1 ratio). Interventions Inpatient Supervised Exercise sessions were conducted for 15 minutes once a day on Postoperative Day (POD) 1 and 2 in the ward. Home-based Exercise involved 30-minute remote exercise sessions at home once a week following discharge, with additional recommendations for daily 30-minute sessions of low to moderate-intensity aerobic exercises and bodyweight exercises. Moreover, the exercise group was provided with an exercise log and instructional videos to record the duration of bodyweight exercises and aerobic exercises. Measurements were taken three times (baseline, POD3, and the first outpatient visit 1 month after surgery). The primary outcome was a Short Physical Performance Battery (SPPB), with secondary outcomes including grip strength, 30-second sit-to-stand (STS), body composition, C-reactive protein (CRP), and quality of life (QOL). Results: A total of 46 (88%) participants (mean [SD] age, 60.2 [12.24] years; 26 [57%] male) completed the trial. Compliance with intervention in-patient exercise was 96% and remote exercise was 79%. The significant difference in SPPB scores of 11.4±1.3 in the exercise group compared with 10.7±1.43 usual care group (mean difference, -1.09 score; 95%CI, -1.7 to -0.4; p=&lt;.001). Moreover, there were significant differences between groups in the STS exercise group 14.3±2.8 usual care group 13.6±4.5 (mean difference, 1.86; 95%CI, -3.3 to -0.4; p=.028), and CRP in POD3 exercise group 66.9±40.73 usual care group 103.7±54.25 (mean difference, -22.54 score; 95%CI, -46.5 to 1.4; p=.016). However, there was no significant difference in grip strength, body composition, and QOL. Conclusions: Postoperative exercise presents as a beneficial strategy to enhance physical recovery in patients undergoing gastrectomy, improving key physical function markers and reducing inflammation. Clinical trial information: NCT06260293 .
Analysis of serum and urine miRNAs as biomarkers of cancer cachexia in pancreatic cancer.
Authors: Mao Okada, Shunsuke Kondo, Yukiko Shimoda Igawa, Tatsuya Yoshida, Milos Havelka, Hiroki Yamaguchi, Yoriko Ando, Motoki Mikami, Yuki Ichikawa, Noboru Yamamoto
Journal: Journal of Clinical Oncology (2025)

773 Background: Cancer cachexia (CC), characterized by anorexia, weight loss and skeletal muscle wasting, is a common complication in patients (pts) with pancreatic cancer (PC). The association of CC with treatment-related toxicity and decreased quality of life has been reported. Although CC is believed to result from systemic inflammation and cancer-induced metabolic changes, the underlying mechanisms remain poorly understood. Early diagnosis of CC is particularly challenging, highlighting the need for reliable biomarkers. We analyzed microRNAs (miRNAs) in serum and urine as potential biomarkers for the early detection of CC in PC. Methods: Clinical information, along with serum and urine samples were collected from pts with PC treated at the National Cancer Center Hospital, Tokyo, from March 2022 to March 2024. CC diagnosis according to Fearon et al: (1) ≥5% weight loss in 6 months, (2) ≥2% weight loss in individuals with a BMI of &lt;20 kg/m², or (3) ≥2% weight loss in pts with sarcopenia. In this study, pts were considered to have CC if they met the definition of CC at enrollment or within six months. Serum and urine extracellular vesicle (EV) miRNA profiles were sequenced by NGS and compared by means of counts per million (CPM). Differential expression of miRNAs between pts with and without CC was investigated by DEseq2. Results: Of the 84 enrolled cases, 73 had sufficient sample volume for NGS assay. After excluding 4 cases with low miRNA read counts and 10 cases with unknown CC status, 59 cases were analyzed. CC was present in 41 pts (69%). Patients’ background was as follows (CC/no CC); median age 70 [IQR:62–75]/ 67 [63–69], male 21/9 pts, cStage {I (7/0), II (1/0), III (18/5), IV (15/13)} pts, median BMI (21.7 [IQR:19.6–24.0]/21.8 [20.7–22.4]) kg/m2, respectively. There were 141 common miRNA species between serum and urine samples, 81 miRNAs unique to serum and 33 unique to urine. The correlation between the common miRNAs was moderate (R = 0.60). No significant differences in miRNA expression were observed between pts with and without CC in serum samples. In urine samples, miR-141-5p was significantly downregulated (log2FoldChange = -0.667, padj = 0.0463), while miR-146b-5p was significantly upregulated (log2FoldChange = 1.03, padj = 0.0463) in pts with CC compared to those without. Conclusions: The results of this study suggest that urine is a suitable biofluid for detecting CC in patients with PC, as differentially expressed miRNAs were not observed in serum. However, the mechanism underlying the superiority of urine over serum in detecting CC remains unclear and should be addressed in future studies.
Phase II single-arm, single-center clinical trial of all-trans-retinoic acid, bevacizumab, and atezolizumab in refractory microsatellite stable colorectal cancer.
Authors: Syed Mohammad Ali Kazmi, Salwan Al Mutar, Radhika Kainthla, Amy Little Jones, Hussna Abunafeesa, David Hsieh, Timothy J. Brown, Nilesh Verma
Journal: Journal of Clinical Oncology (2025)

TPS324 Background: A critical clinical challenge in microsatellite stable (MSS) metastatic colorectal (mCRC) patients is to identify strategies to overcome lack of response to immune checkpoint inhibitors. An immunosuppressive tumor microenvironment comprising myeloid-derived suppressor cells (MDSC), endothelial cells, regulatory T cells, tumor associated macrophages, and cancer associated fibroblasts promotes immune evasion and resistance to these agents. MDSCs are bone marrow derived myeloid cells that suppress T-cell function and promote tumor growth. Among all cancers, mCRC patients have one of the highest frequency of MDSC (CD11b+, CD33+, CD14+ HLA-DRneg) in blood (1). It was demonstrated that altering the MDSC% in the tumor microenvironment by ATRA and anti-VEGF therapy (bevacizumab) can enhance the effects of immune checkpoint inhibitors (2-4). The hypothesis of the current clinical trial is that the combination of ATRA, bevacizumab and atezolizumab will lead to a decrease in MDSC population in tumor microenvironment leading to a clinically meaningful improvement in response rates among refractory MSS mCRC patients. Methods: This is a single-arm, open-label, phase 2 clinical trial combining ATRA, bevacizumab, and atezolizumab in refractory MSS mCRC patients. It will enroll a total of 21 patients over 24 months at UT Southwestern Medical Center that are MSS by PCR or NGS testing or are proficient in immunohistochemical expression of all four mismatch repair enzymes (MLH1, MSH2, MSH6, PMS2). ATRA will be administered orally at 45 mg/m2/day in 2 divided doses on days 1-7 and repeated every 14 days; atezolizumab will be given intravenously on day 1 at 840 mg dose every 14 days, and bevacizumab will be administered intravenously on day 1 at 10 mg/kg dose every 14 days. The first six patients enrolled on this study will contribute to the safety lead-in phase of this study. The primary outcome is to assess the overall response rate by RECIST v1.1. Secondary outcomes include assessment of disease control rate and frequency of adverse events using CTCAE v5.0. Exploratory outcomes include assessment of PFS and OS and collecting blood and tissue samples at defined timelines to study the changes in the MDSC population among responders and non-responders (NCT05999812). 1. Kobayashi, M. et. al., Clin Cancer Res, 2019. 2. Mirza, N., et al., Cancer Res, 2006. 3. Tobin, R.P., et al., Int Immunopharmacol, 2018. 4. Tobin, R.P., et. al., Clin Can Res, 2023. Clinical trial information: NCT05999812 .