tbuckley/cabot-search huggingface dataset:
Clinical characteristics of patients with advanced hepatocellular carcinoma who received long-term treatment with atezolizumab and bevacizumab for more than one year.
Authors: Youngun Kim, Beodeul Kang, Jung Sun Kim, Il-Hwan Kim, Hyeyeong Kim, Won Suk Lee, Yun Beom Sang, Sanghoon Jung, Chan Kim, Hong Jae Chon
Journal: Journal of Clinical Oncology (2024)

532 Background: Atezolizumab plus bevacizumab (Ate/Bev) has become the standard of care since 2020 as a first-line systemic therapy for unresectable hepatocellular carcinoma (HCC). However, studies on patients receiving long-term treatment with Ate/Bev are still lacking. In this study, we evaluated the clinical characteristics and impacts on patients receiving Ate/Bev treatment for more than one year. Methods: We prospectively enrolled 246 patients with unresectable HCC who received Ate/Bev treatment at three tertiary cancer centers in Korea between May 2020 and April 2022. Comparative analyses were performed between patients treated with Ate/Bev for more than one year and those treated for less than one year. Additionally, treatment-related adverse events (AEs), and changes in liver function were evaluated. Results: Of the 246 patients, 69 (28.0%) were treated with Ate/Bev for more than one year. The long-term treatment group showed better Eastern Cooperative Oncology Group performance status, liver function, and lower residual hepatic tumor burden at baseline, compared to the group treated for less than one year. Furthermore, the long-term treatment group had a higher incidence of atezolizumab-related thyroid dysfunction (30.4% vs. 10.7%, p ‹ 0.001), dermatologic toxicity (30.4% vs. 14.1%, p = 0.006), and bevacizumab-related hypertension (43.5% vs. 22.6%, p = 0.002) and proteinuria (68.1% vs. 39.0%, p ‹ 0.001), compared to the less than one-year treatment group. The median time to onset of thyroid dysfunction and dermatologic toxicity after Ate/Bev treatment was 2.8 months and 3.3 months, respectively, while the median time to onset of hypertension and proteinuria was 4.2 months and 6.8 months, respectively. In the long-term treatment group, 30 patients (43.5%) showed an increase in Child-Pugh score, 20 (29.0%) had an increase in Child-Pugh grade during Ate/Bev treatment. Conclusions: The Ate/Bev long-term treatment group had better performance status, liver function, and a lower residual hepatic tumor burden at baseline. Atezolizumab-related immunologic adverse events occurred mostly early in the course of treatment, whereas bevacizumab-related adverse events occurred relatively later. In addition, a fraction of patients experienced deterioration of liver function during long-term Ate/Bev treatment.
Phase I/II clinical trial of regorafenib plus durvalumab (MEDI4736) in patients with chemotherapy-refractory advanced biliary tract cancers.
Authors: Raed Moh'd Taiseer Al-Rajabi, Anup Kasi, Joaquina Celebre Baranda, Anwaar Saeed, Haoran Li, Collin Bruey, Shaun Best, Milind A. Phadnis, Weijing Sun
Journal: Journal of Clinical Oncology (2024)

TPS581 Background: Biliary tract cancers (BTC) are a heterogeneous group of cancers affecting the epithelial lining of the intra- and extrahepatic portions of the biliary tree, ranking as the second most prevalent primary liver cancer after hepatocellular carcinoma. A subgroup of BTC was found to have an abundant tumor specific neoantigen expression, enriched expression of immune related genes and genes regulating inhibitory immune checkpoint proteins. Recent advancements in BTC treatment include the TOPZ-1 trial, which established the survival advantage of adding durvalumab to the gemzar + cisplatin regimen with an estimated 24-month overall survival rate of 24.9% versus 10.4% for placebo. The hazard ratio for progression-free survival favored durvalumab at 0.75 (95% CI, 0.63 to 0.89; P=0.001). Objective response rates also showed improvement, with 26.7% for durvalumab and 18.7% for placebo. Furthermore, single agent regorafenib has exhibited efficacy in patients with refractory advanced metastatic cholangiocarcinoma, particularly in terms of progression-free survival, favoring regorafenib over placebo, the overall toxicity profile was as expected. Regorafenib targets multiple tyrosine kinases and has been reported to show immunomodulatory properties that may counteract tumor-induced immunosuppression, providing a rationale for combining it with checkpoint inhibitors. We believe that modulating the tumor microenvironment with small molecule inhibitors like regorafenib will have synergistic effect when combined with checkpoint-based immunotherapy like durvalumab in patients with chemo refractory BTC. Methods: This study comprises a single-arm, unblinded Phase I/II trial designed to assess the safety and efficacy of the combination therapy involving regorafenib and durvalumab in patients with chemo-refractory advanced BTC. The Phase I portion employed a 3 + 3 design with two dose levels of regorafenib (80 mg and 120 mg) administered in conjunction with 1500 mg IV durvalumab every 28 days. Phase I successfully completed, and the Data Monitoring Committee (DMC) endorsed the continuation of the trial as planned. Eligibility: Histologically confirmed unresectable or metastatic disease. Progressed on at least one line of therapy. May have received checkpoint inhibitor in the past. Inclusion criteria also include ECOG PS 0-1. Objectives:Primary Phase I: Safety of regorafenib in combination with durvalumab.Phase II: Progression-free survival (PFS).Secondary:Disease Control Rate (DCR), Overall response rate (ORR), Overall survival (OS). Statistical Plan: Interim futility testing after one year, halting if conditional power &lt; 20%. Final analysis: PFS and OS via Weibull Regression. Enrollment is currently ongoing with 8 out of 40 patients enrolled.
Clinicopathologic characteristics of patients with early-onset colorectal cancer.
Authors: Maki Takagi, Misato Takao, Nozomi Funatsu, Soichiro Natsume, Daisuke Nakano, Kazushige Kawai, Tatsuro Yamaguchi
Journal: Journal of Clinical Oncology (2024)

74 Background: Although the incidence of colorectal cancer has been declining in the United States in recent years, the incidence of young patients under 50 years of age has been reported to be increasing by several percent per year. Various studies have been conducted to characterize early-onset colorectal cancer (EO-CRC); however, it has been unclear whether it is a different entity from late-onset colorectal cancer (LO-CRC). In this study, we evaluated the clinicopathologic characteristics of EO-CRC in Japan. Methods: This study included 1,336 patients who underwent surgical resection for colorectal cancer at Tokyo Metropolitan Komagome Hospital from January 2015 to December 2019. We performed genetic testing for patients with suspected Lynch syndrome after providing genetic counseling and obtaining informed consent. The study protocol was approved by the Institutional Review Board. Results: Of the 1,336 colorectal cancer patients, 117 (8.9%) had EO-CRC with a median age at the diagnosis of 44 (17–49) years. Tumors were located at right-sided colon in 23 patients and left-sided colorectum in 92 patients with EO-CRC, respectively. The clinical stage of the tumor was I in 19, II in 23, III in 50, and IV in 23 patients with EO-CRC, respectively. Histologically, differentiated type, undifferentiated type, and mucinous carcinoma were 106, 5, and 3 patients, respectively. KRAS mutation was detected in 25.0% and BRAF V600E was detected in 4.3% of patients with EO-CRC. In the microsatellite status, MSI-High was detected in 6 (5.1%) patients with EO-CRC, of whom 3 (2.6%) were diagnosed with Lynch syndrome by genetic testing. Causative genes were MLH1 in 2 patients and MSH2 in one patient. In hereditary tumors, 2 patients with familial adenomatous polyposis were included in addition to Lynch syndrome. On the other hand, 1,219 (91.2%) had LO-CRC with 34.5% of KRAS mutation and 6.4% of BRAFV600E. MSI-High was detected in 69(5.7%) patients with LO-CRC，of whom 5 (0.4%) were diagnosed with Lynch syndrome. Lynch syndrome was significantly more common in EO-CRC (p=0.026). Conclusions: The alterations of KRAS and BRAF tended to be more frequent in EO-CRC. The frequency of hereditary CRC was more frequent in EO-CRC than in LO-CRC.
Prevalence of cancer and alcohol use in patients with exocrine pancreatic insufficiency compared to patients with cystic fibrosis.
Authors: James Peeples, James Gore, Karina G. Romo, Abdullah A. Noor, Gabriel I. Uwaifo
Journal: Journal of Clinical Oncology (2024)

680 Background: Cystic fibrosis (CF), the most prevalent genetic disorder among persons of European decent, is an autosomal recessive disorder due to CFTR gene mutations which lead to abnormally viscid exocrine secretions of the pancreas and other exocrine glands of the body. Exocrine pancreatic insufficiency (EPI) is a condition seen in ~85% of CF patients, in which the pancreas is unable to secrete adequate amounts of digestive enzymes. Although most patients with CF develop EPI, not all cases of EPI are caused by CF. Other risk factors for EPI include acute or chronic pancreatitis which may be triggered by alcohol, among other etiologies. Some studies suggest alcohol use as a possible independent risk factor for development of various cancers. Given these associations, we sought to characterize the prevalence of both alcohol use and cancer in patients with EPI vs patients with CF. Methods: A retrospective observational study was performed using electronic health records in Ochsner System, Louisiana, over a 3 year period: January 2017 to January 2020. Two cohorts were reviewed: patients with EPI excluding CF (n=596) and patients with CF (n=81). Results: While there was no significant difference in the prevalence of cancer at start vs end of the 3 year observation period in the CF cohort (4.1% at start, 7.2% at end), the prevalence of cancer was significantly greater among patients in the EPI cohort, both at start and end of the 3 year period: 15.95% at start, 43.9% at end (p &lt;0.05). Also, while there was no significant change in alcohol use over the 3 year period for the CF cohort, the prevalence of alcohol use was significantly lower in CF cohort (0.45% at start, 2.2% at end) compared to EPI cohort which showed significant increase in alcohol use over the observation period: 7.7% at start vs 16% at end (p &lt;0.05). Conclusions: There was a significantly higher prevalence of cancer in the EPI cohort compared to the CF cohort; while this may be due to higher prevalence of pancreatic cancer associated with EPI compared to CF, it does not explain the entirety of this observation. Not only was there a significantly higher prevalence of alcohol use in EPI cohort compared to CF cohort, but over the 3 year observation there was a 2-fold increase in prevalence of alcohol use within patients who already had a diagnosis of EPI. Within the EPI cohort, the observed increase in cancer prevalence and the increase in alcohol warrant further investigation into which factors unique to EPI patients without CF may modulate these social and health risk indices.
Real-world survival outcomes and treatment patterns in patients (pts) with unresectable hepatocellular carcinoma (uHCC): Results from the OREIOS study.
Authors: Stephen Chan, Valeriy Vladimirovich Breder, Yu Yun Shao, David Tai, Imam Waked, Sandip Ganguly, Ashwaq Alolayan, Ahmed Aboutaleb, Heba Farag, Min-Hee Ryu
Journal: Journal of Clinical Oncology (2024)

449 Background: Recent advances in systemic therapies have revolutionized the management of HCC. However, there is limited real-world data on treatment patterns and survival outcomes in pts with uHCC. OREIOS (NCT05239507) study determined the clinical characteristics, management patterns and survival outcomes in pts with uHCC from 12 countries across Asia, Latin America, and Middle East and Africa. Methods: This non-interventional, retrospective study included pts with Barcelona Clinic Liver Cancer (BCLC) stage B or C unresectable or advanced/metastatic HCC at index date (date of diagnosis), diagnosed between January 2017 and December 2019. We present the clinicodemographic characteristics, treatment patterns, median overall survival (mOS), landmark survival (12 and 24 months), and median progression-free survival (mPFS). Results: A total of 1115 pts (median [range] age: 63 [18.0-97.0] yrs) were assessed; 83.2% (928/1115) were males, 49.1% (422/859) were current or ex-smokers, 21.4% (122/571) consumed alcohol. Most common etiologies were hepatitis B (48.9% [529/1082]), hepatitis C (23.1% [250/1082]) and alcoholic liver disease (6.6% [72/1082]). At index date, 22.3% (249/1115) and 77.7% (866/1115) presented with BCLC stage B and C, respectively with main portal vein invasion in 23.5% (262/1114), &gt;50% liver involvement in 23.1% (250/1081) and extrahepatic metastases in 48.5% (541/1115). After index date, treatment modalities included systemic therapy (88.2% [992/1112] (including sorafenib [77.5%], nivolumab [21.3%], lenvatinib [19.8%], regorafenib [15.6%]), transarterial chemoembolization (TACE) (20.8% [232/1115]), and surgery (2.6% [29/1115]). The mPFS was 6.6 (95% CI 6.0, 7.2) months and mOS was 13.1 (95% CI 11.6, 14.2) months. Conclusions: Our study provides real-world data on treatment patterns and reports poor prognosis with pts reaching a mOS of ∼13 months. With novel agents and combination therapies being approved for uHCC, integrating them in routine care is important to improve survival. Alongside, further real-world studies are warranted for evaluating the change in treatment patterns and prognosis. Clinical trial information: NCT05239507 . [Table: see text]
Multisite external validation of blood test for colorectal neoplasia screening in a majority average-risk screening cohort of 449 subjects.
Authors: Shai Friedland, Drew Watson, Douglas K. Rex, Ashish Nimgaonkar, Zhen Zhang, Alex Atkins, Ben Hsieh, Jr-Ming Lai, Stephen Su, Jen-chia Wu, Hung-Jen Shao, Jessica Tesoriero, Lindsey Hannah, John McGowan, Daniel S Mishkin, Ekta Gupta, Samir Gupta, John J. Sninsky, Rui Mei
Journal: Journal of Clinical Oncology (2024)

66 Background: The FirstSight CRC screening blood test was previously shown to have sensitivities of 92.1% and 54.5% for CRC and AA at a specificity of 90.6% for 1,038 subjects from 18 clinical sites. In this report, we describe the independent external validation of the predefined FirstSight CRC screening blood test with new subjects from 16 sites dispersed across the US, 4 of which are new and did not participate in the previous study. Methods: The validation study included subjects from two sources: Average-risk, asymptomatic screening subjects from screening clinics supplemented with diseased-only subjects from surgical oncology centers. Blood was drawn before bowel prep for colonoscopy or treatment. External validation as well as Monte Carlo cross-validation (MCCV) methods were used to evaluate the performance of the pre-defined FirstSight assay, algorithm, and clinical thresholds in this independent external validation set. Results include sensitivity and specificity to detect CRC and AA and 95% confidence intervals. Results: The study cohort (55.2% female; mean age 56.9 yrs.) consisted of 449 subjects (White 61.7%; Black 14.5%; Hispanic 18%; AAPI and Middle Easterners 5.8%). The majority of them, 376 (84%), were asymptomatic, average-risk screening subjects (including 1 CRC, 53 AA, and all 322 negative subjects). An additional 73 (16%) diseased subjects (39 CRC and 34 AA) were enriched due to low disease prevalence. The FirstSight algorithm derives a test score from 0 to 100 as a quantitative measure of AA and CRC risk with a cutpoint to assign a binary low- or high-risk designation. The previously described cutpoint of 47.2 yielded a test specificity of 90.0%, and 90.0% and 52.9% sensitivity for the detection of CRC and AA, respectively. Here we report a higher cutpoint 50 with identical sensitivities but improved specificity to 90.7%. Point estimates of sensitivity and specificity, including CRC staging, and Clopper-Pearson exact 95% confidence intervals based on the external validation results are presented below. Conclusions: An external validation included 449 subjects from a multi-site, majority average-risk CRC screening study successfully validated the FirstSight Blood Test’s high performance as previously established with 1,038 subjects. The results bring forth confidence in the Test’s reproducibility in a large-scale clinical trial. Clinical trial information: NCT05127096 . [Table: see text]
Genomics and transcriptomics of pancreatic adenosquamous carcinoma.
Authors: Brooke Elizabeth Kania, Yasmine Baca, Gregory Riedlinger, Sanjay Goel, Emil Lou, Benjamin Adam Weinberg, Moh'd M. Khushman, Joanne Xiu, Pat Gulhati
Journal: Journal of Clinical Oncology (2024)

691 Background: Pancreatic cancer (PC) is anticipated to become the 2nd leading cause of cancer-related deaths by 2030. Pancreatic adenosquamous carcinoma (PASC) is a rare subtype of PC with histology including squamous adenomatous features (≥30% squamous histology), while pancreatic squamous cell cancer (PSCC) consists purely of squamous cells. We evaluated genomic, transcriptomic and prognostic differences between PASC, PSCC and pancreatic ductal adenocarcinoma (PDAC). Methods: 8951 PC tumors (83 PASC, 22 PSCC &amp; 8846 PDAC) tested at Caris Life Sciences with WTS (Illumina, Novaseq) and NextGen DNA sequencing (NextSeq, 592 genes and NovaSeq, WES) and IHC were analyzed. Immune cell fraction was calculated by QuantiSeq. Overall survival (OS) analysis (time of tissue collection to last contact) was obtained from insurance claims and calculated with KM method. Statistical significance was determined using Chi-square/Fisher-Exact and adjusted for multiple comparisons (q&lt;0.05). Results: No age or sex differences were seen between PDAC (median 68yo) and PASC (median 68.5yo), however PSCC was more prevalent in younger pts (median 62.5yo, q&lt;0.05). Mutation rates of CDKN1B (3% vs 0.2%), SF3B1 (8 vs 2%), PTEN (5 vs 0.8%), BCL9 (4 vs 0.4%), AXIN1 (4 vs 0.2%) and CASP8 (3 vs 0.2%) and amplifications of AKT2 (5 vs 2%), ZNF384 (1 VS 0.1%), HMGA2 (7 vs 0.7%) and ROS1 fusions (1 vs 0.04%) all trended higher in PASC than PDAC (p&lt;0.05). Several YAP signaling and squamous differentiation genes were significantly differentially expressed among histologies (table). PD-L1 IHC was higher in PASC vs PDAC (37 vs 14%, q&lt;0.05); with a trend towards higher MSI-H (6 vs 1%) &amp; TMB-H (6 vs 2%) in PASC vs PDAC (p&lt;0.05). Higher infiltration of CD4 + T cells into the TME was seen in PASC vs PDAC (non-zero %, 73% vs 23%, q&lt;0.05). Several immune genes ( CD274, IDO1, LAG3, &amp; CTLA4) had higher expression in PASC vs PDAC (fold change 1.3-3.1, q&lt;0.05). The MAP kinase pathway activation score (MPAS) was lower in PASC vs PDAC (median score -0.48 vs 0.25), while the IFN gamma signature was higher in PASC vs PDAC (median -0.24 vs -0.33) [both q&lt;0.05]. There was increased OS for PASC compared to PSCC (12.6 vs 4.7 mo, HR=0.43, CI=0.25-0.75, p=0.002); no significant difference in OS was observed between PASC and PDAC. Conclusions: This is the largest molecular profiling analysis of PASC, which is characterized by unique genomic alterations, and is associated with higher PD-L1 expression, immune related gene expression, CD4+ T cell infiltration and IFN gamma signature, and lower MAPK activation. PASC is associated with better OS compared to PSCC. These findings may provide subtype-specific therapeutic opportunities for PASC and PSCC pts.[Table: see text]
Prospective study to assess taste related to eating disorders during chemotherapy using a dietary app: OISHY study.
Authors: Toshiharu Hirose, HIroko Abe, Hayato Tsuchiya, Honoka Funaki, Kazuki Hamada, Tetsuya Nojiri, Ken Kato
Journal: Journal of Clinical Oncology (2024)

302 Background: Adverse events (AE) such as nausea, vomiting, dysgeusia, oral mucositis, and anorexia during chemotherapy can lead to eating disorders. Nutritional specialists provide supportive care by intervening based on these symptoms. However, individual patients have diverse taste complaints, making assessment difficult. Recently, dietary apps have been developed that offer dietary recommendations and enable patients to record meals based on the patient's condition. In this study, we utilized a dietary app to record meals and quantify taste. The aim was to objectively assess the details of taste for AEs related to eating disorders. Methods: Patients diagnosed with gastrointestinal cancer between March 2021 and June 2022 at our hospital who received chemotherapy were included in the study. Patients searched for food recommendations using the dietary app according to their symptoms and recorded their meals. For each meal, the amount of intake and taste were recorded. Taste was recorded on a scale of 1-100 for sweet, salty, sour, bitter, umami, and spicy, with 1 indicating the weakest flavor and 100 the strongest. AEs that could cause eating disorders were assessed using CTCAE ver. 5.0 and taste was examined for each AE. Results: A total of 18 patients (9 with esophageal cancer, 8 with colorectal cancer, and 1 with gastric cancer) were enrolled in this study. Palliative chemotherapy was given to 9 patients and preoperative chemotherapy to 9. AEs (any grade) related to chemotherapy-induced eating disorders were anorexia in 13 patients, dysgeusia in 12, nausea in 10, and oral mucositis in 7. Median food intake and taste scores for all patients were 95.7%, sweet 50.1, salty 50.6, sour 49.6, bitter 48.4, umami 52.0, and spicy 49.5. When assessed by CTCAEs, the following were found: anorexia 94.0%, sweet 49.8, salty 50.7, sour 48.5, bitter 48.0, umami 52.0, spicy 47.0; dysgeusia 95.7%, sweet 48.3, salty 51.3, sour 48.0, bitter 46.2, umami 53.2, spicy 45.6; nausea 92.0%, sweet 50.1, salty 50.6, sour 49.4, bitter 45.8, umami 50.3, spicy 46.4; and oral mucositis 94.1%, sweet 47.6, salty 50.4, sour 47.0, bitter 48.9, umami 52.0, spicy 47.0. Compared with all patients, in anorexia there were no obvious sensitivities for any tastes, but the intake amount was decreased. In dysgeusia, patients less strongly perceived sweet and spicy, but more strongly perceived salty and umami. In nausea, the patients ate less and less strongly perceived bitter, umami, and spicy. In oral mucositis, sweet and sour tastes were perceived less strongly. Conclusions: By using a dietary app, detailed taste could be quantified for chemotherapy AEs related to eating disorders. Further large-scale studies may be needed. Clinical trial information: UMIN000046647 .