tbuckley/cabot-search huggingface dataset:
Assessing risk stratification in long-term outcomes of rectal neuroendocrine tumors following endoscopic resection: A multicenter retrospective study.
Authors: Yeonjoo Seo, Han Hee Lee, Jin Il Kim
Journal: Journal of Clinical Oncology (2024)

42 Background: The detection of rectal neuroendocrine tumors (NETs) has increased with advances in diagnostic endoscopy. Endoscopic resection (ER) is a highly effective treatment option for rectal NETs confined to . We aimed to analyze the long-term outcomes of patients with rectal NETs after ER. Methods: In this multicenter retrospective study, we included patients who underwent ER of rectal NETs from 2009 to 2018 and were followed for ≥12 months at five university hospitals. We classified the patients into three risk groups according to the clinicopathological status of the rectal NETs: low, indeterminate, and high. The high-risk group was defined if the tumors have any of the followings: size ≥ 10 mm, lymphovascular invasion, muscularis propria or deeper invasion, positive resection margins, or mitotic count ≥2/10. Results: In total, 346 patients were included, with 144 (41.6%), 121 (35.0%), and 81 (23.4%) patients in the low-, indeterminate-, and high-risk grouprespectively. In the high-risk group, seven patients (7/81, 8.6%) received salvage treatment 28 (27–67) days after the initial ER. There was no extracolonic recurrence in any of the 7 patients. During the follow-up period of all included patients, 1.1% (4/346) had extracolonic recurrences at 56.5 (54–73) months after initial ER. Three of these patients (75%) were at a high risk without salvage treatment. The risk of extracolonic recurrence was significantly higher in the high-risk group than in the other groups (p=0.039). Conclusions: The prognosis of patients who underwent ER for rectal NETs was favorable. Physicians should be concerned about the possibility of metastasis during long-term follow-up of high-risk patients and consider salvage treatment. [Table: see text]
Circulating exosomal microRNA signature to predict peritoneal metastasis in patients with advanced gastric cancer.
Authors: Yuma Wada, Masaaki Nishi, Kozo Yoshikawa, Chie Takasu, Takuya Tokunaga, Toshihiro Nakao, Hideya Kashihara, Toshiaki Yoshimoto, Mitsuo Shimada
Journal: Journal of Clinical Oncology (2024)

396 Background: Despite of radical operation, about half of gastric cancer (GC) patients with advanced GC develop peritoneal metastasis (PM) and the patients with PM has poor prognosis. However, because staging laparoscopy was high invasive procedure for the patients, identification of PM by using liquid biopsy can be useful in patients with GC. Methods: We analyzed two genome-wide miRNA expression profiling datasets (GSE164174 and TCGA). We prioritized biomarkers in pretreatment plasma specimens from clinical training and validation cohorts of patients with GC. We developed an integrated exosomal miRNA panel and established a risk-stratification model, which was combined with miRNA panel and currently used tumor markers (CEA, CA19-9, CA125, and CA72-4 levels). Results: Our comprehensive discovery effort identified a 4-miRNA panel that robustly predicted the metastasis, with an excellent accuracy in TCGA dataset (AUC=0.86). We successfully established a circulating exosomal miRNA panel with remarkable diagnostic accuracy in the clinical training (AUC=0.85) and validation (AUC=0.86) cohorts. Moreover, the predictive accuracy of the panel was significantly superior to conventional clinical factors (P&lt;0.01), and the risk-stratification model was dramatically superior to the panel and currently used clinical factors for predicting PM (AUC=0.94, univariate: OR = 77.00, P &lt; 0.01; multivariate: OR = 57.71, P = 0.01). Conclusions: Our novel risk-stratification model for predicting PM has a potential for clinical translation as a liquid biopsy assay in patients with GC. Our findings highlight the potential clinical impact of our model for improved selection and management of patients with this malignancy.
Fruquintinib with PD-1 inhibitors versus TAS-102 with bevacizumab in late-line mCRC: A retrospective cohort study based on propensity score matching.
Authors: Rongrong Li, Xiao-Lin Yang, Zhen-yang Liu, Hui-Jun Zhou, Xian-Li Yin, De-Yu Zeng, Hua Shen, Yi-Dong Zeng, Fang Xiang, Ke Li, Shao-Feng Jiang, Wu Liu
Journal: Journal of Clinical Oncology (2024)

95 Background: Fruquintinib with PD-1 inhibitors (FP) and TAS-102 with bevacizumab (TB) are two common therapies for patients with previous-treated metastatic colorectal cancer (mCRC). However, it’s still not clear that which therapy can bring better prognosis. Methods: This is a retrospective cohort study conducted in Hunan Cancer Hospital. Patients (pts) with mCRC who had received at least the 2 nd line treatment were eligible. Propensity score (PS) would be calculated to balance the baseline characteristics of two arms. Overall survival (OS) was set as the primary endpoint. Results: From July 2019 to October 2022, 106 eligible pts in total were enrolled. According to the treatment received, 72 and 34 pts were respectively allocated into FP cohort and TB cohort. With a global median follow-up of 14, the crude OS was 19.4 (95% CI: 17.9-NA) mo in FP cohort vs. 11.6 (10.0-17.2) mo in TB cohort. The HR of FP was 0.384 (95% CI: 0.192-0.769, TB as reference). Multivariate Cox regression showed that the adjusted HR was 0.323 (95% CI: 0.149-0.704), which was adjusted with sex, age greater than 65 yr, ECOG-PS, resection of primary lesion, radiotherapy history, location of lesion (left or right), metastases (liver, lung, and bone), and current line (3 or later). With PS, we performed three statistical methods, namely inverse probability weighting, PS matching (the sample size was 49 vs. 29 after matching), and additional adjustment for PS with multivariate cox regression. The HRs of FP were 0.437 (95% CI: 0.200-0.953), 0.446 (95% CI: 0.201-0.990), and 0.339 (95% CI: 0.153-0.748), respectively. Subgroup analysis indicated that FP demonstrated lower HR in subgroup of male (0.296, 95% CI: 0.117- 0.753), right-sided lesion (0.177, 95% CI: 0.043- 0.736), liver metastasis (0.291, 95% CI: 0.112- 0.756), and current line greater than 3 (0.303, 95% CI: 0.113- 0.812). Additionally in the raw set, the ORR was 16.67% vs. 8.82% (OR FP =2.067, 95% CI: 0.602-9.559), and the DCR was 93.06% vs. 73.53% (OR FP =4.824, 95% CI: 1.518-17.030). Conclusions: FP demonstrated robustly lower HRs for OS in both crude and PS analysis. Likewise, FP showed better OS and DCR in pts with late-line mCRC than TB, which suggested FP might be a better therapy in late-line mCRC.
Advantages of robotic surgery for advanced gastric cancer in short-term outcomes: A single-center retrospective study using propensity score matching.
Authors: Masaru Komatsu, Masahiro Yura, Mitsumasa Yoshida, Takumi Habu, Hiromi Nagata, Takahiro Kinoshita
Journal: Journal of Clinical Oncology (2024)

343 Background: The advantages of robotic gastrectomy (RG) for gastric cancer are being demonstrated. However, there are few reports that have focused on advanced gastric cancer and examined the advantages of RG for laparoscopic gastrectomy (LG). We conducted the following study to clarify the advantages of RG for advanced gastric cancer. Methods: This single-center retrospective study reviewed the clinical data of 1531 patients who underwent either RG or LG from 2014 to 2023. 473 patients were with clinically diagnoses as having advanced gastric cancer. They were divided into the RG group (n = 143) and the LG group (n = 330). Propensity score matching was employed to adjust the background of the two groups, as covariates of age, gender, BMI, surgical method (distal gastrectomy/total gastrectomy), stage (early cancer/advanced cancer), and presence or absence of preoperative chemotherapy. Then, the treatment results were compared and examined. Results: 130 patients in each group were extracted by propensity score matching. There were no significant differences in age, gender, and ECOG-PS between the two groups. Compared to the LG group, the RG group had more cases with deeper invasion depth ≥T3 (93.1 vs 84.6%, P = 0.04), more D2 dissection (96.9 vs 88.5%, P = 0.01), and longer operative time (339.5 vs 294.5min, P &lt;0.01). The number of retrieved lymph nodes was larger (49.5 vs. 44, P &lt;0.01) in the RG group. Importantly, in the RG group, there were fewer complications with Clavien-Dindo (CD) classification ≥Grade II (11.5 vs 21.5%, P = 0.04) and CD classification ≥Grade III (0.8% vs 6.9%, P = 0.01). Postoperative hospital stay was shorter (8 vs 9 days, P = 0.01) in the RG group. Conclusions: RG for advanced gastric cancer has the potential to reduce complications compared to LG. Long-term survival outcomes should be investigated.
The interim analysis of a single-arm, open-label, phase II study investigating ALLEN regimen (durvalumab plus albumin paclitaxel and lenvatinib) in patients with metastatic pancreatic cancer (mPC).
Authors: Meixia Chen, Zhifang Li, Qianyi Ming, Yan Zhang, Kaichao Feng, Qian Mei, Yang Liu, Weidong Han
Journal: Journal of Clinical Oncology (2024)

658 Background: Metastatic pancreatic cancer is a leading cause of cancer death worldwide with limited treatment options. Durvalumab, the anti- PD-L1 inhibitor has revealed remarkable efficacy in solid malignancies including hepatobiliary cancers. We conducted a study to evaluate the efficacy and safety of a combination therapy of Durvalumab, Albumin paclitaxel and Lenvatinib (ALLEN Regimen) in patients with mPC. Methods: This open-label, single-center, single-arm, phase Ⅱ clinical trial investigated patients with metastatic pancreatic cancer. Durvalumab (1000mg IV, q3w), albumin paclitaxel(180-220 mg/m 2 IV q3w) and lenvatinib (8mg PO QD) were given regularly until disease progression. The primary endpoint was objective response rate (ORR) evaluated by investigators according to RECIST 1.1. The secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and treatment-related adverse events (TRAEs). Results: Between September 2021 and September 2023, seventeen patients with ECOG score 0-2 were enrolled, including 8 patients (47%) who were refractory to at least one systemic chemotherapy.The median follow-up was 6.0 months (95% CI 4.0, 8.4). 17 patients were evaluable, with a median age of 58 years. 9 patients (52.9%) were male. The ORR and DCR were 64.7% and 94.1%, respectively. The median PFS was 7.8 months (95% CI 3.1, 11.4), and the median OS was 8.1 months (95% CI 4.7, 13.5). TRAEs (all grades) occurred in 16 (94.1%) patients. The most common grade 1-2 TRAEs were nausea 8 (47.1%), diarrhoea 5(29.4%), peripheral sensory neuropathy 3 (17. 6% ) and hypertension 3(17.6% ). No grade 3 or higher TRAEs occurred. Conclusions: The ALLEN regimen demonstrated promising antitumor activity and well acceptable toxicity in metastatic pancreatic cancer. Further randomized controlled studies will be required in a larger patient population. Clinical trial information: NCT05327582 .
Patient-reported outcomes: The unmet needs of the gastrointestinal cancer community.
Authors: Martha Raymond, Margaret-Ann Simonetta
Journal: Journal of Clinical Oncology (2024)

731 Background: According to the World Health Organization International Agency for Research on Cancer, gastrointestinal (GI) cancers account for 1 in 4 cancer cases and 1 in 3 cancer-related deaths worldwide. An estimated 4.8 million new cases of GI cancers and 3.4 million related deaths occur annually. Understanding the need for increased GI cancer awareness, patient education and support, the GI Cancers Alliance developed a series of engagement activities for the GI cancer community as a needs assessment to identify critical gaps in support services, fragmented education, and disease awareness. Methods: Our 12-month patient-reported outcomes (PRO) research included an online anonymous survey, individual and small group interviews, focus groups, advisory boards, and an interactive workshop at the 2023 American Society of Clinical Oncology annual meeting. 1,122 patients participated during this 12-month PRO research period. Participants reported being diagnosed with one of the following GI cancer primary tumor types: Anus (3%), Appendix (2%), Bile Duct (6%), Colon (19%), Esophagus (7%), Gallbladder (5%), Gastric (14%), GI NET / GI Carcinoid Tumor (3%), Liver (7%), Pancreas (6%), Small Intestine (4%), Rectum (23%), Unknown primary location (1%). Results: Overarching areas of unmet need include: health disparities throughout the care continuum for underserved populations (21%); lack of adequate precision oncology patient education, including biomarker education and testing (19%); the rise of early-age onset (EAO) in GI cancers and the unique needs of the young adult (YA) population (18%); nutritional wellness education (17%); insufficient support for family caregivers and caregiver respite services (16%) scarcity of patient-centered care and adequate patient-clinician communication (11%). Conclusions: Our PRO research underscores the unmet needs and gaps in support services of the GI cancer community. Our global call to action includes partnering with our 100+ member organizations to amplify the patient voice and patient-lived experience, and cross-collaboration with our community of advocates, patients, caregivers, and clinicians. Our shared call to action and continued collaboration provides a greater impact for our GI cancer community to help meet patient needs and eliminate critical gaps in services.
Comparing first-line (1L) atezolizumab plus bevacizumab (A+B) to lenvatinib (L) or sorafenib (S) in patients with unresectable hepatocellular carcinoma (uHCC): Findings from the National Veteran Health Administration (VHA) database.
Authors: David Edward Kaplan, Amie Tan, Cheryl Xiang, Fan Mu, Sarika Ogale, Sairy Hernandez, Jiayang Li, Yilu Lin, Lizheng Shi, Amit G. Singal
Journal: Journal of Clinical Oncology (2024)

446 Background: The approval of A+B has reshaped the treatment paradigm for patients with uHCC, establishing a new standard of care for 1L uHCC treatment. The VHA is the largest independent healthcare delivery network and the largest provider of liver-related care in the US. We aimed to compare patient characteristics and clinical outcomes between veterans who received 1L A+B and those who received L or S for unresectable HCC. Methods: Using data from the VHA National Corporate Data Warehouse (1/1/2017 - 12/31/2022), we conducted a retrospective cohort study in patients diagnosed with uHCC who initiated A+B after 2020 or initiated L or S after 2018. Child-Pugh (CP) scores were calculated using a previously validated algorithm. Kaplan-Meier and multivariable Cox regression methods were applied to compare overall survival (OS) between the groups. Results: We identified 405 eligible patients who received A+B, 453 received L, and 1,016 received S. Compared with patients receiving L or S, those treated with A+B had a higher proportion of CP A5 (47% and 35% vs. 54%, respectively; both p&lt;0.05), a similar proportion of A6 (30% and 32% vs. 31%, p=0.683 and 0.681, respectively), a lower proportion of B7 (15% and 20% vs. 9%, respectively; both p&lt;0.05), and a greater comorbidity burden as measured by the mean Charlson Comorbidity Index (CCI) (5.8 [L or S] vs 6.6 [A+B], both p&lt;0.05). Median OS (mOS) was 12.8 months (95% CI: 10.6, 17.1) in the A+B cohort, compared to 9.5 months [95% CI: 7.8, 11.4] in the L cohort, and 8.0 months [95% CI: 7.1, 8.6] in the S cohort. In subgroup analyses, longer mOS was observed with A+B than with L or S in CP A patients and those with ALBI grades 1-2A; similar mOS was observed among those with more severe liver dysfunction (Table). In multivariable analysis, A + B was associated with a 26% lower risk of death relative to L (HR=0.74, 95% CI: 0.62-0.88) and 30% lower risk of death compared to S (HR = 0.70, 95%CI 0.60-0.82), both p&lt;0.001. Conclusions: In a real-world VHA experience with A+B among diverse patient groups, a clinically notable survival benefit was observed with A+B compared to L or S. Future evaluations of the safety of using A+B in patients with greater liver dysfunction, including CP B and cirrhosis, are needed to evaluate the expanded use of A+B. [Table: see text]
Prediction of postoperative recurrence by integrating preoperative ctDNA levels and tumor metastasis volume in patients (pts) with colorectal cancer (CRC) with resectable lung or liver metastasis.
Authors: Hidekazu Oyoshi, Hideaki Bando, Riu Yamashita, Shun-ichiro Kageyama, Satoshi Horasawa, Masaki Nakamura, Takeshi Fujisawa, Kento Tomizawa, Atsushi Motegi, Saori Mishima, Daisuke Kotani, Hiroya Taniguchi, Eiji Oki, Ichiro Takemasa, Takeshi Kato, Yoshiaki Nakamura, Masaki Mori, Adham A Jurdi, Minetta C. Liu, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2024)

183 Background: In pts with CRC, the clinical usefulness of ctDNA testing after curative resection has been strongly suggested. Prognostic biomarkers are also needed for pts with resectable metastases to identify high-risk patients who may be spared unnecessary surgery or local ablation. We aimed to create a prediction model to estimate the risk of post-operative recurrence using an integrated analysis of preoperative ctDNA level and radiographic imaging. Methods: The GALAXY study (UMIN000039205) included 645 pts with newly diagnosed or recurrent CRC with resectable metastatic lesions. Pts without liver or lung metastases and those who had received chemotherapy within 3 months prior to ctDNA measurement were excluded. We used the ratio of preoperative ctDNA levels [mean tumor molecules (MTM)/mL] to tumor metastasis volume (mL) from radiographic imaging (ctDNA/volume) to predict recurrence. Cutoff ctDNA/volume values were determined from receiver operating characteristic curves using Youden index. Pts with above and below the cutoff values were defined as high and low risk, respectively. Disease-free survival (DFS) was calculated from the date of definitive surgical resection to first recurrence or death. Results: In this cohort of 110 pts with liver metastases and 24 with lung metastases, the median follow-up was 13.2 months (range: 0.7-30.9). The cutoff values for the ctDNA/volume model were 0.837 (liver) and 0.496 (lung) MTM/mL 2 . Among the pts with liver metastases, the high-risk group predicted by the ctDNA/volume model had a median DFS of 14.7 months (95% CI: 6.1–not reached) versus not reached (95% CI: not reached–not reached) in the low-risk group (HR = 3.6, P = 0.021). Among the pts with lung metastases, the median DFS was 2.9 months (95% CI: 2.1–not reached) in the high-risk group versus 21.8 months (95% CI: 21.8–not reached) in the low-risk group (HR = 21.0, P &lt; 0.0001). The high-risk group had a significantly higher cumulative recurrence at 6 months (17% and 67% in pts with liver and lung metastases, respectively) versus the low-risk group (0%, P = 0.012 and 6%, P &lt; 0.001 in pts with liver and lung metastases, respectively) considering death as a competing risk. Conclusions: The ctDNA/volume model was able to predict postoperative recurrence in CRC pts with liver and lung metastases. Ongoing and future studies will further optimize the model by incorporating other clinicopathologic factors associated with postoperative CRC recurrence. [Table: see text]
The mechanistic study of cancer-associated adipocytes promoting colorectal cancer peritoneal metastasis via FKBP5/UCP1-mediated lipid metabolism reprogramming.
Authors: Yue Zhang, Chengzhi Huang, Xueqing Yao
Journal: Journal of Clinical Oncology (2024)

178 Background: Colorectal cancer (CRC) is a prevalent malignant tumor globally, with peritoneal metastasis as a significant late-stage dissemination pathway, severely impacting patient prognosis. Recent research increasingly suggests the critical role of lipid metabolism within the tumor microenvironment in tumor progression. Cancer associated adipocytes (CAAs), a vital component, contribute to tumor progression, yet the exact molecular mechanisms remain unclear. We aim to explore the role of CAAs in CRC peritoneal metastasis and their specific regulatory mechanisms. Methods: In this study, we analyzed clinical samples from 312 CRC patients to assess the expression levels of FKBP5 and UCP1 proteins in tumor-adjacent tissues. Purified exosomes from co-cultured adipocytes and tumor cells, along with exosomes from ordinary tumor cells, underwent miRNA profiling via sequencing to evaluate exosomal miR-200a-3p expression. We established FKBP5 stable knockdown (FKBP5 -/- ) transgenic mouse models, organotypic co-culture models, and patient-derived xenograft (PDX) models. Through experiments involving metabolomics, mass spectrometry, immunoprecipitation, western blotting, and qPCR, we investigated the role of the miR-200a-3p/FKBP5/PPARγ/UCP1 signaling pathway in CAAs in CRC peritoneal metastasis. Results: After co-culturing adipocytes and tumor cells, we observed brown adipocyte differentiation, resulting in significant downregulation of FKBP5 protein expression. FKBP5 exhibited a strong association with UCP1 expression. Tumor cells highly expressed miR-200a-3p, released via exosomes into the tumor microenvironment and internalized by adipocytes. Within adipocytes, miR-200a-3p orchestrated metabolic reprogramming via the FKBP5/PPARγ/UCP1 pathway, inducing brown adipocyte differentiation, generating CAAs. CAAs released FFAs, promoting tumor peritoneal metastasis by activating tumor cell surface G-protein coupled receptors (GPCRs). Conversely, miR-200a-3p inhibition in tumor cells yielded opposing effects. In a spontaneous mouse model of colorectal cancer using azoxymethane (AOM)/dextran sulfate sodium salt (DSS), FKBP5 -/- mice exhibited increased brown adipocyte content in the tumor microenvironment, along with notably higher spontaneous colorectal tumor numbers and sizes compared to wild-type mice. Conclusions: This study elucidates the pivotal role of CAAs in the peritoneal metastasis of CRC, confirming the regulatory role of the FKBP5/UCP1 pathway-mediated lipid metabolism reprogramming in this process. These findings offer a fresh perspective for further exploration of the molecular mechanisms underlying CRC peritoneal metastasis, and provide a theoretical foundation for the identification of novel therapeutic targets.