tbuckley/cabot-search huggingface dataset:
Artificial intelligence-based model for recurrence prediction after local excision on whole slide images in T1 low rectal cancer.
Authors: Chengzhi Huang, Jiarui Su, Xueqing Yao
Journal: Journal of Clinical Oncology (2024)

24 Background: According to current guidelines, patients with resected specimens showing high-risk features are recommended for additional surgery after local excision of T1 colorectal cancer, despite the low incidence (~7%) of recurrence. However, surgical resection in patients with low rectal cancer (RC) is challenging and may compromise anal function, leading to a low quality of life. To reduce unnecessary surgical resection for these patients, we utilized artificial intelligence to develop and validate a prediction model for the risk of recurrence in T1 low rectal cancer patients. Methods: H&amp;E-stained whole slide images (WSIs) were scanned for local excision (endoscopically or transanally minimally) specimens of 507 consecutive patients with T1 low rectal cancers that were locally resected at 4 hospitals between 2005 and 2015. The area under the receiver operating characteristic curve (AUROC), specificity and sensitivity were used to evaluate the performance of the model for the risk of recurrence, and an external validation cohort was to verify the applicability of the model. Results: We constructed a prediction model using convolutional neural networks (CNN) without incorporating clinical features. The model yielded good discrimination and calibration, achieving a 5-year recurrence-free survival AUROC of 0.90 (95% confidence interval [CI]: 0.86–0.93), sensitivity of 0.91 (95% CI: 0.84–0.96), and specificity of 0.82 (95% CI: 0.78–0.88) through fivefold cross-validation. Additionally, the AI avoided 25.7% of unnecessary additional surgery compared to the current guidelines. Conclusions: We proposed a novel prediction model for the risk of recurrence in T1 low RC patients to assist physicians in determining whether additional surgery is required after local excision of T1 low RC.
Liquid biopsies for faster diagnosis of suspected advanced pancreatic and biliary tract cancers: ACCESS, a UK innovation programme.
Authors: Lauren Jones, Justin Mencel, Reed Mullen, Sofia Sardo Infirri, Alan MacDonald, Charlotte Victoria Fribbens, Sheela Rao, Asif Mahmood, Daniel Galloway, Sanjay Gupta, Georgina Chadwick, Ian Chau, Melody Ni, Terri Patricia McVeigh, Sanjay Popat, Michael Hubank, David Cunningham, Angela Joy George, Naureen Starling
Journal: Journal of Clinical Oncology (2024)

614 Background: Tissue diagnosis in biliary tract (BTC) and pancreatic (PC) cancer is challenging due to anatomical location and patient (pt) factors (frailty, sepsis); approximately 25% of invasive biopsies are nondiagnostic, requiring repeat procedure. Most BTC and PC pts present with advanced disease. In stage III and IV solid tumours, Guardant 360 (G360) 74 gene panel liquid biopsy (LB) detects ctDNA in 80%/85% of BTC/PC. ACCESS is a real-world innovation programme evaluating the impact of adding G360 to the current invasive diagnostic pathway for suspected BTC/PC in 6 hospitals in West London; (n=240). Methods: This is a pre-planned interim analysis of the first sequential 65 pts with G360 in ACCESS. Patients were age&gt;18 years, ECOG ≤ 2 with high radiographic suspicion of stage III/IV BTC or PC without histological diagnosis at registration or other malignancies within 3 years. Positive LBs were reviewed at molecular tumour board with 4 pre-specified levels of diagnostic certainty: diagnostic/consistent/possibly/not consistent. Tumour board review followed. Endpoints include repeat biopsy rate, change in time to diagnosis, quality of life, health economic assessment and patient satisfaction. Results: 64 patients were analysed (1 excluded). 50% female, median age 73 years (43-94), suspected cancer sites 14%/77%/9% BTC/PC/either BTC or PC. Suspected stage III/IV disease 38%/62%. ctDNA detection rate was 80%/100%/82% in overall cohort/BTC/PC. Most commonly detected LB alterations in suspected BTC/PC were TP53, APC, ATM, CDK/TP53, KRAS, CDKN2A, ARID1A. In BTC and PC, diagnostic method was liquid biopsy alone/liquid and tissue biopsy/tissue alone in 16%/49%/33%. 17% had repeat biopsy. Sensitivity/specificity of cancer diagnosis (all-comers) using liquid biopsy was 86% (95% CI 73.3-94.2)/38.5% (95% CI 13.9-68.4). Conclusions: There is a high ctDNA detection rate with high level diagnostic certainty, promising for future genomic transformation of BTC/PC diagnostic pathways, potentially reducing repeat invasive biopsies, speeding up diagnosis, facilitating precision therapy, with ACCESS defining a blueprint for molecular integration of liquid biopsies. Full recruitment is planned to complete in March 2024.
Colon cancer screening disparities among limited English proficient patients during implementation of patient navigation services.
Authors: Rebecca Yao, Gregory Jenkins, Jessica Grimm, James Hill, Amenah Agunwanba, Jane Njeru
Journal: Journal of Clinical Oncology (2024)

17 Background: Age-appropriate colon cancer screening has long demonstrated effectiveness in reducing colon cancer incidence and mortality. However, despite a gradual rise in compliance with colon cancer screening, significant disparities remain, particularly among patients with limited English proficiency (LEP). Multitarget stool DNA (MT-sDNA) testing (Exact Sciences, Madison, WI) has been available over the past decade in the United States as a lower-cost and non-invasive option for screening. In 2019, Exact Sciences began to offer patient navigation services comprising outbound phone, text, and e-mail reminders, and inbound phone support (&gt;200 languages) with all MT-sDNA orders. In this study, we aimed to evaluate the disparity in successful MT-sDNA testing between LEP and EP patients in a time frame when patient navigation services were active. Methods: We performed a retrospective cohort study of patients 45-75 years old enrolled in the primary care setting of our institution who received an order for MT-sDNA screening during a period in which patient navigation services began to be offered. A multi-state Cox model was constructed with time to MT-sDNA or other CRC screening predicted by English proficiency accounting for age and gender. Wald tests were used to test the association of CRC screening completion and English proficiency. Rates of completion of MT-sDNA screening and other CRC screening following MT-sDNA test ordering were calculated using the Kaplan-Meier method. Results: Of the 5016 patients evaluated and referred for multitarget stool DNA testing from May 1 st , 2021, and May 1 st , 2022, 154 patients were of LEP, and 4862 were English proficient (EP). At 180 days following a MT-sDNA test order the rate of completion for the LEP patients was 50.2% (95% CI: 42.8-58.7%) versus 70.3% (95% 69.1-71.6%) for EP individuals (p=0.001). A small portion of individuals also completed another type of CRC screen, 3.3% for LEP and 2.5% for EP (p=0.99). Conclusions: This study is consistent with the existing research demonstrating LEP as a significant demographic group linked with decreased participation in cancer screening. Our findings indicated that despite the availability of patient navigation services, individuals with LEP were still less likely to complete an MT-sDNA test successfully when compared to those with EP. [Table: see text]
Surgeon fatigue in robot-assisted and laparoscopic gastrectomy for gastric cancer: Exploratory prospective observational study ancillary to JCOG1907 randomized controlled trial (JCOG1907A1).
Authors: Keiichi Fujiya, Masanori Terashima, Ryosuke Kita, Junki Mizusawa, Rie Makuuchi, Takeshi Omori, Yoshitomo Yanagimoto, Taro Isobe, Toshiyasu Ojima, Yoshiyuki Kawashima, Haruhiko Fukuda, Yukinori Kurokawa, Narikazu Boku, Takaki Yoshikawa
Journal: Journal of Clinical Oncology (2024)

TPS422 Background: Fatigue is being increasingly recognized as an important factor in surgical procedures, because it leads to errors in surgeons' decisions and reduced operating efficiency. In comparison to laparoscopic surgery, robot-assisted surgery is expected to reduce surgeon fatigue due to ergonomic adjustments, comfortable sitting positions, minimal restriction of instrument movement, and stable visualization. The aim of this study is to assess surgeon fatigue and explore the superiority of robot-assisted gastrectomy over laparoscopic gastrectomy in surgeon fatigue. Methods: This study is conducted as a prospective observational study ancillary to a randomized controlled phase III trial investigating the superiority in safety of robot-assisted gastrectomy over laparoscopic gastrectomy for clinical stage T1-4aN0-3 gastric cancer (JCOG1907: UMIN000039825). The lead surgeon and the first assistant performing surgeries as protocol treatment in JCOG1907 were included. Surgeon fatigue is quantitatively assessed using multiple assessment tools. The primary endpoint is the average NASA-Task Load Index (NASA-TLX) value for the lead surgeons. Secondary endpoints include six individual parameters of NASA-TLX, visual analog scale assessments for fatigue, advanced trail-making tests, and continuous heart rate variability measurements for lead surgeons and first assistants. The primary analysis compares surgeon fatigue between robot-assisted and laparoscopic surgery. Secondary analyses examine the association between surgeon fatigue and various factors, such as surgeon and patient background, and surgical findings, as well as cross-correlations among measures of surgical fatigue. In addition, the association between surgeon fatigue and postoperative complications and its impact on long-term survival outcomes is also evaluated. The sample size is 500 surgical cases, with a planned accrual period of 2 years. This study was initiated in April 2023 and registered at the University Hospital Medical Information Network as UMIN000052120. As of August 2023, 52 cases (10.4% of the planned accrual) have been enrolled in the study. Clinical trial information: UMIN000052120 .
Phase 2 study of <i>nab-</i>sirolimus in patients with well-differentiated and advanced/metastatic neuroendocrine tumors of the gastrointestinal tract, lung, or pancreas.
Authors: Michael J. Demeure, Allen Lee Cohn, Tara Elisabeth Seery, Li Ding, Willis H. Navarro, Andrew Scott Paulson
Journal: Journal of Clinical Oncology (2024)

TPS601 Background: Neuroendocrine tumors (NETs; ~2% of all malignancies) commonly arise from the gastrointestinal (GI) tract, pancreas, and lung, often presenting as metastatic disease. The PI3K/Akt/mTOR pathway is implicated in the pathogenesis and progression of NETs. Everolimus, an oral mTOR inhibitor (mTORi), is an option for treatment of NETs of the GI tract, lung, or pancreas but response rates observed in the RADIANT -3 and -4 studies were modest at 4–10%. nab-Sirolimus is a mTORi that utilizes nanoparticle technology to preferentially target tumors and is approved in the USA for malignant perivascular epithelioid cell tumor. In preclinical animal models, nab-sirolimus demonstrated higher intratumoral drug accumulation, improved target suppression, and stronger antitumor activity relative to equal weekly doses of sirolimus and everolimus, warranting further exploration of nab-sirolimus. This study will evaluate efficacy/safety of nab-sirolimus in patients with advanced/metastatic NETs. Methods: This phase 2, multicenter, open-label, single-arm study (NCT05997056) will enroll approximately 21 adults (≥18 years) with functional or non-functional, well-differentiated, locally advanced unresectable or metastatic NETs of the GI tract, lung, or pancreas who have received ≤2 prior lines of therapy, excluding somatostatin analogs (SSTa).Patients with functional NETS are eligible if they have been on a stable dose of SSTa for ≥12 weeks and had disease progression during SSTa treatment. Eligible patients must have ≥1 measurable target lesion (per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1), Eastern Cooperative Oncology Group performance status score 0 or 1, and adequate organ function/hematologic parameters.They are not permitted to have received prior mTORi, including nab-sirolimus, or to have tumors with known inactivating TSC1 or TSC2 alterations. Patients will receive nab-sirolimus 100 mg/m 2 by intravenous infusion on days 1 and 8 of 21-day cycles. Treatment will continue until disease progression or unacceptable toxicity, or until discontinuation based on investigator or patient discretion.The primary endpoint is investigator-assessed objective response rate per RECIST v1.1. Secondary endpoints include duration of response, disease control rate, time to response, progression-free survival, overall survival, and safety. Exploratory endpoints include correlation of baseline molecular biomarkers with clinical outcomes. Analysis of study objectives will be descriptive. Study site activation is underway with the first patient on study anticipated for the 3 rd quarter of 2023. Clinical trial information: NCT05997056 .
A scoring system for selecting nivolumab or irinotecan in the later-line chemotherapy for advanced gastric cancer: A Japanese multicenter retrospective study.
Authors: Yusuke Amanuma, Takeshi Suzuki, Takeshi Kawakami, Masahiko Aoki, Yoshiyuki Yamamoto, Keitaro Shimozaki, Hironaga Satake, Masanori Nojima, Narikazu Boku, Daisuke Takahari
Journal: Journal of Clinical Oncology (2024)

266 Background: Although Nivolumab (NIVO) or Irinotecan (IRI) monotherapy is one of the later-line chemotherapies for the advanced gastric cancer (AGC) patients, there are no prospective data of their comparison, and no indicators for selection of them. Methods: Clinical data of AGC patients treated with NIVO or IRI as later-line were collected from 7 institutions between September 2015 and September 2018. Efficacy of the two treatment groups was compared in the entire cohort and in the propensity score matching cohort. Factors which affect the prognosis were explored by multivariate analyses and the scoring system was developed using Cox regression. Results: In the analysis of entire cohort (317 patients), the median OS was 4.8 months (95% CI: 3.6–5.8) in the NIVO group and 5.9 months (95% CI: 4.9–7.2) in the IRI group, and those were 4.8 months (95% CI: 3.6–5.7) and 6.0 months (95% CI: 4.5–7.2) in the analysis of the propensity score matching cohort (248 patients), respectively. There were no differences in OS. We developed a risk score involving 1-Neutrophil to Lymphocyte Ratio (NLR), 2-age, 3-ECOG performance status, 4-peritoneal metastasis, 5-gastrectomy, and 6-liver metastasis to assess potential effect modification. Based on the result, IRI was favored in the higher-risk group (≥4 points, with double weight to 2, 3, and 4) for both OS/PFS. In contrast, NIVO was better OS/PFS in the lower-risk group (&lt;1 point). Conclusions: According to the real-world data from multicenter in Japan, NIVO and IRI generally showed equivalent outcomes. The scoring system we explored may be useful for selecting appropriate later-line chemotherapy, either NIVO or IRI.
Incidence and genomic characteristics of gene fusions in a large Chinese colorectal cancer cohort.
Authors: Furong Kou, Lin Shen, Jian Li, Zhenghang Wang, Ting Xu, Juanjuan Qian, Enli Zhang, Lisha Cui, Lijun Zhang, Xicheng Wang
Journal: Journal of Clinical Oncology (2024)

192 Background: Gene fusion is rare in colorectal cancer (CRC). With the advent of fusion-targeted therapeutics, such as entrectinib for NTRK fusion and selpercatinib for RET fusion, the identification of gene fusions holds clinical significance. Reports providing a comprehensive description of fusions in CRC are limited, and understanding the molecular characteristics of CRC with fusions will contribute to efficient fusion screening. Here, we investigate the incidence and genomic features of gene fusions in a large Chinese CRC population. Methods: We systematically analyzed next-generation sequencing results of tumor tissue from 5534 CRC patients between January 2020 and August 2023. The sequencing panel covers 769 cancer-related genes and can detect fusions, single nucleotide variants and indels, and microsatellite instability (MSI). Statistical significance was determined using chi-square test. Results: Overall, the median age of patients was 62 years (inter-quartile range [IQR]: 53-70), and 40% were female. Gene fusions were detected in 4.4% (242/5534) of all the patients. The incidence is 0.98% (54/5534) if only reported clinically actionable fusions are considered. The median age of the 242 fusion-positive patients was 64 years (IQR: 54-70), and 43% were female. The most highly detected potentially actionable gene fusions were NTRK (0.89%) and FGFR (0.81%), accounting for 39% of the fusion-positive patients. The other fusion genes were ERBB2 (0.52%), RET (0.38%), BRAF (0.31%), EGFR (0.27%), ALK (0.22%), MET (0.09%) and ROS1 (0.07%). Consistent with previous reports, patients with MSI-High were more likely to have fusions compared with those with microsatellite stability (MSS) or MSI-Low (9.9% vs 4.0%, p &lt; 0.001). Besides, RAS or BRAF mutated patients accounted for 59% of the cohort, of whom 2.5% (83/3273) had fusions detected, while 7.0% (159/2261) of the RAS and BRAF wildtype patients had positive fusions ( p &lt; 0.001). Moreover, 404 (7.3%) patients had RNF43 splice or truncating mutations, and gene fusions were detected in 12.9% of these patients. Combining these markers increased the detection rate of fusions, with 28% (33/118) of the RAS/ BRAF wildtype and MSI-H patients having fusions detected. Furthermore, in patients with wildtype RAS/BRAF and MSI-H and RNF43 splice or truncating mutations, the fusion detection rate was as high as 49% (32/65), including 24 patients with actionable fusions of definite clinical significance. Conclusions: Gene fusions were detected in 4.4% of the Chinese CRC population and tended to occur in patients with wildtype RAS/BRAF, MSI-H, or RNF43 mutations. Combining the mutational status of RAS, BRAF, and RNF43 along with MSI status can improve the fusion detection rate and help select candidates for fusion testing and targeted therapy.
Examining the prevalence of anxiety and depression in surgical oncology patients: Results of a prospective cohort study.
Authors: Judy Li, Nazanin Khajoueinejad, Elad Sarfaty, Allen Yu, Samantha Troob, Alison Buseck, Camilo Correa, Deepa Magge, Umut Sarpel, Noah A Cohen
Journal: Journal of Clinical Oncology (2024)

734 Background: Prospective data assessing prevalence of anxiety and depression in a diverse surgical oncology population are currently lacking. Psychological distress may affect patient outcomes in the postoperative setting. The General Anxiety Disorder (GAD) and Patient Health Questionnaire (PHQ9) surveys are validated instruments to assess severity of anxiety and depression, respectively. We aimed to determine the prevalence of anxiety and depression using validated screening tools, and assess associations between anxiety and depression with clinical outcomes in patients presenting to our surgical oncology clinic. Methods: A prospective, surgeon-blinded study was conducted to assess associations of anxiety and depression with postoperative outcomes in patients with histologically proven malignancy who underwent surgical intervention. Preoperatively, the GAD and PHQ9 surveys were administered to evaluate for anxiety and depression, respectively. Frailty level was also assessed using the validated Risk Analysis Index (RAI-C) survey. Postoperative outcomes included rates of ICU admission, 30- and 90-day readmissions, postoperative complications classified by Clavien-Dindo score, and disposition to home versus rehabilitation facilities. Outcomes were compared between different groups as defined by the severity of anxiety and depression. Results: 191 patients met inclusion criteria. The cohort was stratified into three groups by severity of anxiety and depression. Overall, 59 (31%) patients reported at least moderate anxiety as defined by a GAD score ≥5, with 30 (15.7%) patients reporting severe anxiety (GAD score ≥ 10). Similarly, 62 (32%) patients reported at least mild depression as defined by a PHQ9 score ≥5, with 21 (11%) patients experiencing moderate to severe depression (PHQ9 ≥ 10). No difference was detected in length of stay, ICU admission, 30- and 90-day readmission, and postoperative complications. Preoperative frailty, as defined by RAI-C score &gt;21, was also not associated with anxiety or depression. Marital status of single or widowed was found to be significantly associated with mild depression (p=0.027) and moderate to severe depression (p=0.028), respectively. Conclusions: While anxiety and depression were not found to be significantly associated with postoperative outcomes, they are prevalent in surgical oncology patients, affecting approximately one-third of our patient population. The GAD and PHQ9 surveys are validated instruments that can be administered easily to identify surgical oncology patients with psychological distress. Comprehensive evaluation of psychological well-being, in conjunction with a thorough social evaluation, can identify those patients who may benefit from referral to supportive resources.
Oxaliplatin desensitization in patients with GI malignancies: Experience from a tertiary cancer center.
Authors: Jacqueline Connell, Panagiotis J. Vlachostergios, Joseph Thomas David Williams, Jurgees Hassan, Wasat Mansoor, Saifee Mullamitha, Richard Hubner, Michael Braun, Mark Saunders, Jorge Barriuso, Tom Waddell, Nooreen Alam, Konstantinos Kamposioras
Journal: Journal of Clinical Oncology (2024)

89 Background: Oxaliplatin hypersensitivity is not uncommon in patients with gastrointestinal (GI) cancers receiving chemotherapy. The use of oral premeditations (dexamethasone, cetirizine and famotidine) starting 24 hours before treatment and continuing for a total of three days, further intravenous premedication (dexamethasone, chlorphenamine and famotidine) 30 minutes before treatment and the gradual administration of oxaliplatin over 6.5 hours in four separate escalating doses (desensitisation protocol) is commonly used in such cases. While desensitisation is an option, especially in severe cases, responses and survival outcomes upon rechallenge are not well described. Methods: A retrospective chart review of patients with various GI malignancies who received oxaliplatin-based desensitisation chemotherapy after a severe drug reaction between October 2019 and October 2022 at a single cancer centre was performed. Clinicopathological characteristics and oncological outcomes were assessed. Results: Forty-four patients with a median age of 61 years (range 38-81) were studied. The majority had a diagnosis of CRC (n=22; 50%), followed by oesophago-gastric (n=19; 4%), appendiceal (n=1), cholangiocarcinoma (n=1), and cancer of unknown primary (n=1). More than two thirds of patients (n=32, 73%) were treated with palliative intent. The most common regimens associated with oxaliplatin hypersensitivity reactions after a median of 3 cycles (range 1-10) were FOLFOX (n=24, 55%), CAPOX (n=18, 41%), FLOT (n=1) and FOLFOXIRI (n=1). Seven patients (16%) had another reaction after desensitisation, leading to discontinuation of treatment. Thirty-seven patients (84%) completed treatment as planned. Treatment outcomes after desensitisation included 5 (11%) patients with no evidence of disease (NED) after adjuvant treatment, 16 (37%) patients with disease control, including 3 (7%) partial responders (PR) and 13 (30%) patients with stable disease (SD), and 23 (52%) patients with progressive disease (PD). Conclusions: Oxaliplatin desensitisation is feasible with low discontinuation rates and leads to acceptable oncological outcomes. All patients should be offered desensitisation to allow continuation of active systemic therapy.