tbuckley/cabot-search huggingface dataset:
A prospective study of radiofrequency ablation combined with systematic neoadjuvant therapy in the treatment of recurrent hepatocellular carcinoma (RANT study).
Authors: Kai Feng, Kuansheng Ma, Qiang Wang, Feng Xia, Huaqiang Bi, Zhiyu Chen, Leida Zhang
Journal: Journal of Clinical Oncology (2024)

e16240 Background: Radiofrequency ablation (RFA) is an important minimally invasive approach for recurrent HCC, but is hampered by the high recurrence rate and limited ablation volume for the tumor. This study aims to evaluate the efficacy and safety of systemic neoadjuvant therapy (tislelizumab combined with lenvatinib/bevacizumab) combined with RFA in the treatment of recurrent HCC. Methods: This prospective, single-arm, phase II trial enrolled patients with recurrent resectable HCC who has a history of liver resection or RFA (the number of lesions ≤ 3, the largest lesion ≤ 3 cm, as demonstrated by contrast enhanced CT/MRI). Prior to RFA, patients received tislelizumab (200 mg, q3w, iv) and lenvatinib (body weight≥60 kg, 12 mg; &lt;60 kg, 8 mg, qd, po) or bevacizumab (15mg/kg) for two cycles. RFA was scheduled in one week after the systemic neoadjuvant therapy. After 4-8 weeks of surgery, patients continued to receive tislelizumab and lenvatinib /bevacizumab for 6 to 12 months. Primary endpoint was one-year relapse-free survival (RFS) rate and one-year overall survival (OS) rate. Secondary endpoints were objective response rate (ORR) by mRECIST, and adverse events (AE). Results: From November 2021 to October 2023, 20 patients (median age, 57 years) were enrolled, all Child-Pugh A and ECOG PS 0, mostly males (95%) and HBV infection (90.0%). 19 patients had received 2 cycles systemic neoadjuvant therapy and RFA was successfully performed, 1 patient achieved complete response after systemic treatment and didn't perform RFA. According to mRECIST, the ORR was 50% (95%CI: 27.20%-72.80%), and the DCR was 100 % (CR 1, PR 8, SD 11). After a median follow-up of 8.5 months (interquartile range 5-21 months), tumor recurrence was detected in 2 patients, 1 patient died of disease recurrence. The estimated 12-month RFS rate and OS rate were 76.9% (95%CI 31.2%, 94.3%) and 100%, respectively. Median RFS and OS were not reached. So far the safety of neoadjuvant treatment was satisfied, no grade 4 or above treatment-related-adverse events (TRAEs) were observed. Grade 3 TRAEs were reported in 3(13.04%) patients. Frequently occurring adverse eventswere grade 1-2, including total bilirubin increased (39.13%), elevated aspartate aminotransferase (30.43%), and elevated alanine aminotransferase (30.43%). Conclusions: Radiofrequency ablation combined with systematic neoadjuvant therapy exhibited promising efficacy and favorable safety for recurrent HCC. Clinical trial information: NCT05277675 .
Video Laryngoscopy for Surgical Endotracheal Intubation
Authors: Kurt Ruetzler, Nikolaos Skubas, Daniel I. Sessler
Journal: JAMA (2024)

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Epidemiology, survival and new treatment modalities for intrahepatic cholangiocarcinoma (IHCC).
Authors: Yating Wang, Yasir Alsaraf, Sai Samyuktha Bandaru, Susan Elizabeth Lyons, Leo Edward Reap, Zhiyong Yu, Qian Yu
Journal: Journal of Clinical Oncology (2024)

e16217 Background: Intrahepatic cholangiocarcinoma (IHCC), a rare biliary tract cancer, has been rising in incidence and is associated with poor survival. With the advent of new treatment modalities and various ongoing research, population-based perspective can be helpful to reflect the progress in managing this deadly disease and provide updated outcome information as a reference for comparison during upcoming clinical studies. We would like to provide a 20-year update on incidence and survival with reference to landmark trials, with a focus on survival outcomes of the recent 5 years for future insights. Recent and ongoing clinical trials will be discussed. Methods: This study extracted population data from the Surveillance, Epidemiology, and End Results (SEER) database. Age-adjusted incidence rate (AAIRs) and survival rate (SR) trends were calculated from January 2000 to December 2020 using 22 registries for the US population. Incidence and survival rates were collected from the SEER database, reported per 100,000 population and age adjusted to the 2020 US standard population. The annual percent change (APC) was used to report long term trends. Results: In this analysis of 19,948 IHCC patients, the AAIR increased from 0.49 per 100,000 in 2000 to 1.38 in 2020 (APC 6.94, 95% CI 6.32 to 7.56), with a notable decline from 2019 to 2020. Incidence rates overall displayed an uptrend course across subgroups divided by sex, race, age, and disease stage. The age-adjusted mOS climbed from 5.28 months in 2000 to 9.3 months in 2013, maintaining between 8.0-9.0 months after 2013. Using 2010 as a cutoff, when the ABC-02 trial was published, the decade-based mOS increased from 6.55 in 2000-2010 to 9.06 in 2010-2020, which remained statistically significant at 1-year, 3-year, and 5-year OS. During 2015-2020, the overall mOS was 8.8 months, with mOS of 24.3 months, 12.1 months, and 5.4 months for local, regional, and distant stages, respectively. Conclusions: These results indicate a steady rise in IHCC incidence since 2000, consistent across all subgroups. Survival rates have improved since 2000 but stabilized after 2013, following the publication of the ABC-02 trial published in 2010, which used systemic gemcitabine and cisplatin for unresectable iHCC. Updated survival data from 2015 onwards will serve as a reference of comparison for forthcoming clinical trials.
A study of risk factors and clinico-pathological profile of patients with cervical cancer at BPKIHS: A descriptive cross-sectional study.
Authors: Ramesh Shrestha
Journal: Journal of Clinical Oncology (2024)

e17515 Background: Cervical cancer is the cancer with highest incidence and mortality among females in Nepal according to GLOBOCAN data 2020. The aims of this study was to evaluate the risk factors and clinico-pathological profile of patients with cervical cancer attending Department of Gynaecology, BPKIHS, Dharan, Nepal. Methods: It was a descriptive cross-sectional study conducted from April, 2019 to February, 2022 among seventy-nine patients with histological diagnosis of cervical cancer after ethical approval. Results: The mean age of these patients was 54.99±12.81 years. The commonest presenting symptom was postmenopausal bleeding (65.8%) and the commonest histological type was squamous cell carcinoma (87.3%). The commonly associated risk factors among them were illiteracy (88.6%), poor local hygiene (78.5%), postmenopausal status (72.2%) and poor socio-economic status (41.8%). The mean age at marriage and first pregnancy were 18.45 (SD=2.32) years and 19.47 (SD=2.51) years respectively. More than one-fourth (29.1%) of the patients had more than or equal to 5 children. Only three (3.8%) patients had undergone cervical cancer screening once in their lifetime.Most of them (n=66; 83.5%) had locally advanced disease at diagnosis. Altogether, sixty-seven (84.8%) patients were referred outside for radiation treatment. Among the surgically treated patients, twelve (63.2%) patients subsequently required dual treatment. Conclusions: Illiteracy, poor hygiene, low socio-economic status, patient’s delays, poor screening programmes, multiparity, early age at marriage and first child birth etc. are the factors requiring major focus to reduce the burden of cervical cancer in developing countries like Nepal.
Phase II study of tislelizumab combined with concurrent chemoradiotherapy for locally advanced cervical cancer.
Authors: Shanshan Ma, Yong Zhang, Fang Wu, Li Jiang, Tingting Zhang
Journal: Journal of Clinical Oncology (2024)

e17523 Background: Concurrent chemoradiotherapy (CRT) is the standard treatment for locally advanced cervical cancer (LACC). However, local recurrence and distant metastasis are the main modes of treatment failure in LACC, especially for patients with stage IIIA ~IVA as well as patients with large masses (&gt;4cm) and regional lymph node metastasis. This study aimed to evaluate the efficacy and safety of tislelizumab (anti-PD-1 antibody) combined with concurrent chemoradiotherapy for locally advanced cervical cancer. Methods: Eligible patients were age 18-75 years, ECOG performance status of 0-1 and untreated cervical cancer (2018 FIGO stage IIIA, IIIB, IVA, or cervical tumor diameter &gt; 4cm with regional lymph node metastasis, or paracervical invasion with regional lymph node metastasis). All patients received CRT plus tislelizumab 200mg Q3W for 1 year or disease progression or intolerable toxicity. The CRT includes at least 4 cycles of cisplatin 40mg/m 2 QW + EBRT 45~50Gy/25f then BT 28~30Gy/4~5f. The primary endpoint was tumor regression ratio before brachytherapy. Secondary endpoints were 3-month and 6-month objective response rate (ORR), 1-year and 3-year OS and PFS, safety. Results: From August 24, 2022 to February 4, 2024, 30 patients were enrolled. 25 patients completed CRT and were available for evaluation. The median age was 59 years (range 40-75). The tumor regression ratio before brachytherapy was 90.6%. The ORR at 3 and 6 months were 100%, The OS and PFS rate at 1 year were 100%. The main adverse effect was neutropenia (36% for grade 3-4 and 20% for grade 1-2). Radiation enteritis incidence was 64% and were grade 1-2. Other adverse effect such as nausea, vomiting, and dizziness occurred during CRT and could be alleviated after symptomatic treatment. No immune-related adverse events were observed. Conclusions: Our results suggest that Tislelizumab combined with concurrent chemoradiotherapy showed valuable antitumor activity and controllable safety in LACC. We will keep strictly implementing our study protocol for further PFS and OS. Clinical trial information: NCT05588219 .
Efficacy and safety of arterial FOLFOX chemotherapy plus anti-PD-(L)1 immunotherapy as first-line treatment for unresectable intrahepatic cholangiocarcinoma: A propensity score matched analysis.
Authors: Yue Hu, Ning Lyu, Ming Zhao
Journal: Journal of Clinical Oncology (2024)

e16189 Background: This study aimed to evaluate the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) plus anti-programmed death (ligand)-1 [PD-(L)1] immunotherapy compared to systemic chemotherapy (SCT) plus anti-PD-(L)1 immunotherapy as first-line treatment for patients with unresectable intrahepatic cholangiocarcinoma (uICC). Methods: In this retrospective study, unresectable treatment-naive ICC patients who were treated with HAIC plus anti-PD-(L)1 immunotherapy [HAIC+αPD-(L)1] or SCT plus anti-PD-(L)1 immunotherapy [SCT+αPD-(L)1] were included. The clinical characteristics, therapeutic outcomes and adverse events (AEs) of patients between the two groups were compared. The propensity score matching (PSM) was performed to minimize biases between groups. Results: From January 2019 to January 2023, a total of 182 patients were enrolled, including 147 patients in HAIC+αPD-(L)1 group and 35 patients in SCT+αPD-(L)1 group. After PSM, 61 and 26 patients were included in the HAIC+αPD-(L)1 and SCT+αPD-(L)1 groups, respectively. The HAIC+αPD-(L)1 group showed longer median overall survival (OS) and progression free survival (PFS) than the SCT+αPD-(L)1 group (OS: 14.5 vs 10.5 months, P = 0.019; PFS: 6.4 vs 10.1 months, P = 0.020). The disease control rate of HAIC+αPD-(L)1 group were higher than those of SCT+αPD-(L)1 group (91.8% vs 69.2%, P = 0.007). The overall incidence of adverse events (AEs) was comparable between the two groups, but the HAIC+αPD-(L)1 group showed a lower incidence of grade 3~4 AEs related to anemia, weight loss and fatigue. Conclusions: HAIC plus anti-PD-(L)1 immunotherapy had acceptable toxic effects and might improve outcomes compared to SCT plus anti-PD-(L)1 immunotherapy as first-line treatment for patients with uICC.
A machine learning–based radiomics approach to predict MUC4 mutation and response to immunotherapy in cholangiocarcinoma.
Authors: Yunlu Jia, Xiao Luo, Junli Wang, Jian Ruan
Journal: Journal of Clinical Oncology (2024)

e16203 Background: The immunogenicity of MUC4 made it a tumor antigen for immunotherapeutic interventions in cholangiocarcinoma (CCA). Identifying CCA patients with elevated MUC4 expression would be crucial for MUC4-targeted immunotherapies and the prediction response to immunotherapy. Methods: In this retrospective study, 55 CCA patients who received first-line treatment with pembrolizumab in combination with gemcitabine plus cisplatin (GP) chemotherapy were enrolled. Enrolled patients underwent surgery before, and their postoperative specimens were subjected to whole exome sequencing and proteomic sequencing, and matched magnetic resonance imaging (MRI) data were collected. We employed a random forest classifier based on radiomic features to predict the status of key genes mutation including MUC4 and tested it on an internal and an external validation CCA cohort. Odds ratio of MUC4 expression for objective response to pembrolizumab plus GP was tested with logistic regression analysis. Association of MUC4 expression with progression-free survival (PFS) and overall survival (OS) was analyzed with a Cox proportional hazard regression. Results: A radiomics nomogram that incorporates radiomics signature and MUC4 mutation showed good calibration and discrimination in the training cohort (AUC = 0.762), internal validation cohort (AUC = 0.812) and external validation cohort (AUC = 0.801). The radiomics nomogram was an independent preoperative predictor of overall and recurrence-free survival. High expression of MUC4 portended significantly lower overall and recurrence-free survival than decreased MUC4 expression levels (P &lt; 0.001). Findings from cell experiments revealed targeting MUC4 with bosutinib showed inhibitory effects on cell proliferation and promoted apoptosis. Additionally, the combination of bosutinib with a PD-1 inhibitor increased the inhibitory effect. Investigating the feasibility of translating these findings into clinical trials for patients with CCA is an important next step. Conclusions: The integration of MUC4-based immunotherapy and incorporating radiomics-based biomarkers could significantly advance personalized medicine and contribute to more effective treatment strategies for CCA patients.
ctDNA for clinical decision support in pancreatic cancer.
Authors: BENJAMIN ASCHERMAN, Neda Amini, Shruti Koti, Daniel King
Journal: Journal of Clinical Oncology (2024)

e16354 Background: Circulating tumor DNA (ctDNA) is increasingly used to inform therapeutic decisions and its applicability to pancreatic cancer is emerging. We explore the adoption of ctDNA profiling in patients presenting to our pancreatic cancer clinic to help guide localized and metastatic pancreatic cancer treatment. Methods: This was an IRB-approved retrospective cohort study of Signatera ctDNA profiling among patients with pancreatic cancer at Northwell Health between October 2021 and September 2023. Patients received ctDNA testing at various treatment timepoints and were categorized according to clinical context: neoadjuvant, adjuvant, surveillance, radiographic relapse, and metastatic. Average ctDNA level and conversion rates were calculated for each group. Results: There were 203 tests completed among 59 patients representing the following clinical contexts: 36% metastatic disease, 27% in the adjuvant setting, 23% during surveillance, 7% prior to surgery, and 6% after relapse. 43 patients had ctDNA tests that were drawn but were cancelled or could not be performed due to inadequate tissue samples, of which 8 had at least one completed test and were included in final analysis. Of all 27 metastatic patients, 8 patients had tests that were never completed. 46% of all tests were positive, which ranged from 0.3 to 8089 MTM/mL, and averaged 196 MTM/mL. 51% of all patients had ctDNA results that remained positive, 34% remained negative, and 15% changed over time from either positive to negative or vice versa. Median ctDNA level was 0.1 MTM/mL or less for patients who were tested prior to surgery or during adjuvant treatment or surveillance and the median ranged from 0.0-67.1 for patients with metastatic disease or relapse. All ctDNA tests sent after radiographic relapse also tested positive. Conclusions: ctDNA testing was most commonly performed in patients with localized disease on adjuvant chemotherapy, and in those with metastatic disease at time of diagnosis, who also had the highest rates of positive tests by stage at diagnosis. Given all patients tested during relapse had positive tests, ctDNA may be an early predictor of disease progression in patients with negative tests on surveillance. When tissue is limited, such as in metastatic patients who are less likely to undergo surgery, production of the ctDNA assay may be hindered. A prospective, larger scale, and more longitudinal study would add greater power and clinical context.
Body mass index (BMI) as a prelude to hepatocellular carcinoma (HCC) and metabolic dysfunction–associated steatohepatitis (MASH) risk factors in patients with no identified risk factor for developing hepatocellular carcinoma (HCC).
Authors: Layal Al Mahmasani, Marinela Capanu, Amitabh Srivastava, Joanne F. Chou, Jinru Shia, Imane H. El Dika, Amin Yaqubie, James J. Harding, Eileen M. O'Reilly, Ghassan K. Abou-Alfa
Journal: Journal of Clinical Oncology (2024)

e16193 Background: Common risk factors for hepatocellular carcinoma (HCC) include viral hepatitis (hepatitis B and hepatitis C), alcoholic liver disease, and metabolic dysfunction-associated steatohepatitis (MASH). Non-risk factored HCC has been suggested where patients who do not have common risk factors develop HCC (Journal of Clinical Oncology Volume 35, Number 15_suppl, May 2017). This is described more commonly among young, females more than males. Is this a misdiagnosis or a truly non-factored risk? Methods: Patients diagnosed with histology confirmed HCC between years 2014 and 2017 with none of the known HCC risk factors, were assessed part of our previous effort add to more recent gathered data at Memorial Sloan Kettering (MSK). In an institutional IRB approved retrospective study, demographic and treatment data in addition to DNA sequencing were compiled and evaluated. Detailed clinical and genomic information was abstracted from the medical record. Pathology data was reviewed (AS). Results: A total of 428 patients diagnosed with HCC were identified, of whom 18 (4.2%) patients had no identifiable HCC risk factors. Fourteen patients were females (78%), and four were males (22%). Median age at diagnosis was 59 years (range 18-77 years). All 18 patients did not meet any of the clinical and/or radiologic alleged criteria for a diagnosis of MASH. The average body mass index (BMI) was 27.9 kg/m2 (16.7-54.4). Six patients (33%) had BMI greater than 30 kg/m2, and five (28%) patients had BMI ranging from 25 to 29.9 kg/m2. Three patients had diabetes mellitus. With the lack of non-tumorous liver cancer surrounding tissue, only three patients had mild steatosis documented on pathology. At the molecular level, few somatic mutations were detected including TERT and CTNNB1 in 37% of cases. No germline mutations were identified in 4 tested patients. Conclusions: Among 18 patients diagnosed with HCC with presumed no or unknown risk factors we previously reported, average BMI was 27.9 kg/m2. This is in the absence of any clinical and/or radiologic alleged criteria for a diagnosis of MASH. In the presence of subtle clinical and/or radiologic findings suggestive of MASH, evaluating patient’s BMI may be considered as an added variable for evaluation of patients with HCC. We clinicians need to be aware of increased BMI as a possible prelude for MASH and HCC. This is added to an invitation for acquired biopsies to include tumor and normal tissue to assess liver cirrhosis or fibrosis.
Effect of ionizing radiation on JAK/STAT pathway and immune microenvironment in cervical cancer.
Authors: Yongchun Zhang, Yuqi Jiang, Yaping Wu, Lei Zhang, Zhiying Chen, Yingxue Qi, Xiangyu Yin
Journal: Journal of Clinical Oncology (2024)

e17516 Background: STAT proteins play an important role in the development and progression of cervical cancer, and inhibition of the JAK/STAT pathway may be critical for enhancing tumor cell death. Delivering a certain dose of ionizing radiation (IR) directly to the lesion is one of the conventional treatments for cervical cancer. Whether IR will trigger changes in the JAK/STAT pathway and tumor immune microenvironment (TIME) is unknown and continues to be explored. Methods: We collected 30 patients received IR therapy with locally advanced cervical cancer (LACC) at the Affiliated Hospital of Qingdao University. Matched pre-IR and post-IR tumor tissue samples were collected from all patients, and the samples underwent RNA sequencing based on the nCounter platform (NanoString Technologies, Seattle, USA) and protein testing based on immunohistochemistry (IHC) staining. All tumor TIME cell infiltration scores were calculated as arithmetic mean of the constituent genes. P-values were calculated via the T Test. Results: RNA sequencing of tumor tissue from LACC patients before and after IR showed 35 differential genes. The results of GSEA pathway enrichment analysis of differential genes showed that compared with before IR, the IFN-α response pathway, IFN-γ response pathway and epithelial mesenchymal transition pathway were significantly up-regulated and enriched after IR. These three pathways collectively affect changes in the downstream JAK/STAT pathway. Moreover, compared with before IR, the cell infiltration abundance of overall macrophages (P=0.0087) and M2 macrophages (P=0.0043) increased significantly after IR. M1 macrophages also showed an increasing trend, but there was no statistically significant difference. In addition, further verification of changes in several proteins on the JAK/STAT pathway by IHC. The results showed that overall macrophages (P=0.0087) and M1 macrophages (P=0.026), PD-L1 (p=0.003), JAK1 (p=0.021) and STAT3 (p=0.018) were significantly increased after IR compared with before IR. M2 macrophages and STAT1 (p=0.734) also showed an increasing trend, but there was no statistically significant difference. It is worth noting that Kendall's tau-b correlation analysis was used to study the correlation of protein changes. The results found that the changes in PD-L1 expression before and after radiotherapy were related to STAT3 (Kendall's tau-b=0.487, P=0.02), JAK1 (Kendall's tau-b=0.513, P=0.015), there is a strong positive correlation. Conclusions: This study found that IR affects changes in cervical cancer TIME and these changes may promote the transition to an immunosuppressive phenotype. In addition, IR may affect changes in PD-L1 levels through the JAK1/STAT3 pathway. This needs to be further verified by designing large prospective clinical trials in the future.