tbuckley/cabot-search huggingface dataset:
Comparing clinical outcomes between PD-1 and PD-L1 inhibitors plus bevacizumab combined with hepatic arterial interventional therapies in unresectable hepatocellular carcinoma: A single-center real-world study.
Authors: Yangxun Pan, Ze Yuan, Dandan Hu, Minshan Chen, Yaojun Zhang
Journal: Journal of Clinical Oncology (2024)

e16229 Background: Systemic therapies combined with locoregional therapies were considered a potent therapeutic strategy in treating patients with unresectable hepatocellular carcinoma (uHCC). Given the A+T strategy became the first-line treatment for advanced HCC patients, the roles of programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors in the combination therapies for treating patients with uHCC needed to be further discussed. The current study compared the clinical outcomes between PD-1 and PD-L1 inhibitors plus bevacizumab combined with hepatic arterial interventional therapies (HAIT) among patients with uHCC. Methods: From October 2019 to May 2023, 142 uHCC patients were retrospectively analyzed in Sun Yat-sen University Cancer Center, including 73 or 69 patients treated with either PD-1 (PD-1 group) or PD-L1 (PD-L1 group) inhibitors, respectively, combined with HAIT plus bevacizumab. The progression-free survival (PFS) and tumor responses were analyzed per mRECIST. Results: At the data cut-off, the median PFS was 5.5 months (95% CI 5.3-7.1 months) in the PD-1 group and 7.5 months (95% CI 7.0-9.6 months) in the PD-L1 group, respectively ( P=0.280; HR=0.74; 95%CI 0.43-1.28). The PD-L1 group showed a significantly better median intrahepatic PFS (8.1 months, 95%CI 7.6-10.2 months) than the PD-1 group (6.5 months, 95%CI 6.2-9.0 months; P=0.014; HR=0.35; 95%CI 0.16-0.81). The overall response rate (ORR; 49.3% vs. 66.7%, P=0.054), intrahepatic control rates (53.4% vs. 69.6%, P=0.070) and overall disease control rate (DCR; 68.5% vs. 78.3%, P=0.261) showed no significant difference in both groups, while the PD-L1 group demonstrated significantly higher intrahepatic disease control rate than the PD-1 group (76.7% vs. 92.6%, P=0.016). Conclusions: PD-1 and PD-L1 plus bevacizumab combined HAIT shared similar PFS, DCRs, and ORRs in treating uHCC patients. The PD-L1 plus bevacizumab combined with HAIT demonstrated a better intrahepatic control than those of PD-1, which needed further validation at a higher evidence level.
Portal vein thrombosis in gastrointestinal cancers: Insights into prevalence and prognosis—A nationwide inpatient analysis 2018-2020.
Authors: Manasa Ginjupalli, Priya Hotwani, Jayalekshmi Jayakumar, Mrunanjali Gaddam, Rabia Iqbal, Bhavyakumar Vachhani, Ankushi Sanghvi, Anuj Sharma, Dhairya Nanavaty, Vikash Kumar, Jincy Clement
Journal: Journal of Clinical Oncology (2024)

e16382 Background: The relation between cancer and thrombotic events has been well established over the past decade. Cancer is a prothrombotic state and thrombosis is the second most common cause of death in cancer. While portal vein thrombosis (PVT) has been extensively studied in individuals with Hepatocellular Carcinoma (HCC), its significance in other Gastrointestinal (GI) cancers is often overlooked. This study aims to investigate the prevalence and prognostic impact of PVT across various GI cancers. Methods: A retrospective analysis was performed on the National Inpatient Sample database (2018-2020) and the ICD-10 codes to identify the patients &gt; 18 years old with primary diagnosis of GI cancers (pancreatic, HCC, gastric, small intestinal[SI], colorectal). Prevalence of PVT in individual GI cancers and effect of PVT on mortality, length of stay and Hospital cost utilization was studied. Multivariable regression analyses were performed adjusting for demographics, hospital-level characteristics, and relevant comorbidities. These included Age, Sex, Race, obesity, Smoking, Hypertension, Diabetes, CKD, liver disease, CHF, CAD, Hypothyroidism. Results: Our study analyzed data from 2,313,888 individuals with GI cancers, Including HCC, Gastric cancer, SI cancer, colorectal and pancreatic cancer, The incidence of PVT varied across cancer types, with 12.9% in pancreatic cancer, 0.74% in HCC, 0.99% in gastric cancer, 0.47% in colorectal cancer, and 3.6% in pancreatic cancer. Multivariate regression analysis, adjusting for confounders, revealed a significant association between PVT and increased mortality in various GI cancers. Specifically, the odds ratio (OR) for mortality in pancreatic cancer was 1.31 (p &lt; 0.001), in HCC was 1.39 (p &lt; 0.001), in gastric cancer was 1.88 (p &lt; 0.001), and in colorectal cancer was 2.10 (p &lt; 0.001). However, the incidence of mortality in SI cancer did not yield a significant result OR 1.42 [p- value 0.369] [Table 1]. Additionally, Our findings revealed an increase in length of stay and total healthcare resource utilization across all GI cancers for individuals with PVT compared to without PVT. Conclusions: There is a statistically significant effect of symptomatic and asymptomatic PVT on mortality in various other GI cancers in addition to HCC, which has been established and studied widely. Further prospective studies are needed to study the effect of diagnosing PVT earlier in the disease to predict mortality and other major complications in GI cancers.[Table: see text]
The role of neoadjuvant clinical trials in patients with newly diagnosed glioblastoma.
Authors: Danielle A. Bazer, Stuart A. Grossman
Journal: Journal of Clinical Oncology (2024)

e14022 Background: Novel cytotoxic drugs are commonly first studied in patients with solid tumors who have recurrent disease. If high response rates and durable remissions are observed, further studies are conducted in previously untreated cancers where the novel agent can be combined with radiation or administered as neoadjuvant therapy (NAT) to reduce tumor size before surgery or radiation and to limit systemic dissemination. While NAT can provide critical information on response rates and survival in previously untreated patients, it can add toxicities and delay the administration of standard therapies. Neoadjuvant chemotherapy is now standard-of-care in many systemic cancers but is rarely considered in patients with glioblastoma (GBM). This literature review was conducted to describe factors leading to NAT playing an increasingly important role in systemic cancers and a diminishing role in patients with GBM. Methods: Prospective trials published between 1980 and 2023 where patients with newly diagnosed systemic cancers and GBM received NAT prior to radiation were identified in PubMed. Results: During these 43 years, over 5,000 NAT trials in patients with systemic cancers were published. As a result of these studies, NAT is now considered standard therapy for 28 different cancers. In contrast, during the same years only 51 prospective studies were reported evaluating the efficacy of NAT in newly diagnosed GBM. These clinical trials accrued a total of 2,047 patients and evaluated the efficacy of nitrosoureas, temozolomide, platinum-based agents, and targeted therapies. These studies peaked before 2005, when combining temozolomide and radiation was shown to improve survival, and declined thereafter. NAT temozolomide was studied in 12 trials (641 patients) resulting in a median response rate of 35% (range 8.7-51%) and a median overall survival of 12.5 (range 6-22) months. NAT trials in patients with GBM were not associated with unexpected toxicities, major reductions in survival, or poor patient accrual. Conclusions: As in other solid tumors, NAT in patients with GBM is relatively safe and feasible. Enthusiasm for this approach has been limited by the paucity of active agents in recurrent glioblastoma that could be subsequently evaluated in newly diagnosed patients. However, the neoadjuvant setting is ideally suited to rapidly screening novel cytotoxic agents for efficacy as it allows: 1) radiographic response rates in previously untreated patients to be the primary endpoint, 2) small sample sizes, and 3) efficacy results in 2-3 months when patients are transitioned to standard care. Given the well documented safety and feasibility history of using NAT in patients with solid tumors and GBM, this approach has the ability to rapidly identify potentially active, novel cytotoxic agents, especially in patients with MGMT unmethylated, IDH wildtype GBM who are unlikely to benefit from temozolomide.
Understanding the Genetic Basis of Variation in Meiotic Recombination: Past, Present, and Future
Authors: Susan E Johnston
Journal: Molecular Biology and Evolution (2024)

Meiotic recombination is a fundamental feature of sexually reproducing species. It is often required for proper chromosome segregation and plays important role in adaptation and the maintenance of genetic diversity. The molecular mechanisms of recombination are remarkably conserved across eukaryotes, yet meiotic genes and proteins show substantial variation in their sequence and function, even between closely related species. Furthermore, the rate and distribution of recombination shows a huge diversity within and between chromosomes, individuals, sexes, populations, and species. This variation has implications for many molecular and evolutionary processes, yet how and why this diversity has evolved is not well understood. A key step in understanding trait evolution is to determine its genetic basis-that is, the number, effect sizes, and distribution of loci underpinning variation. In this perspective, I discuss past and current knowledge on the genetic basis of variation in recombination rate and distribution, explore its evolutionary implications, and present open questions for future research.
Updated results of perioperative PD-1 antibody toripalimab plus FLOT chemotherapy for locally advanced resectable gastric or gastro-esophageal junction adenocarcinoma: A one-arm open-table phase II trial.
Authors: Hongli Li, Shaohua Ge, Fenglin Zang, Peng Ren, Fuliang Cao, Rui Liu, Yuchong Yang, Tao Ning, Ming Bai, Xia Wang, Zhi Ji, Jingjing Duan, Han Liang, Yi Ba, Ting Deng, Jingyu Deng
Journal: Journal of Clinical Oncology (2024)

e16128 Background: Perioperative chemotherapy is the standard treatment for resectable gastric/gastroesophageal junction (GEJ) adenocarcinoma. Immune checkpoint inhibitors have activity in advanced gastric/GEJ cancer. This trial to assess the efficacy of the addition of toripalimab to FLOT for resectable patients and explore the immune microenvironment prospectively related to treatment response of neoadjuvant immunotherapy by multiplex immunohistochemistry. Methods: This is a prospective, single-arm, investigator-initiated phase II trial. Patients with histologically confirmed, resectable, gastric and GEJ adenocarcinoma (≥ cT2 or cN+) were enrolled to receive 4 pre- and post-operative cycles of toripalimab (240mg, q2w) plus FLOT (docetaxel 50 mg/m 2 ; oxaliplatin 85 mg/m 2 ; leucovorin 200 mg/m 2 ; 5-Fu 2600 mg/m 2 , q2w). The primary endpoint were 3-year disease-free survival rate, overall survival and pathological complete response rate (pCR). Planned sample size of 36 operated patients. if the pCR rate is greater than 16% (n = 6), an additional 20 cases will be added. Multiplex immunohistochemistry is used to quantify in situ biomarker at subcellular resolution. Results: Study accrual completed at August 2022, 55 patients were enrolled, 40M/15F, age 57 (28-76), ECOG 0 (39) and 1 (16). 4 patients had not received surgery were excluded from efficacy analysis (Three patients withdrew consent after two treatment cycles and one refused surgery after 4 cycles pre-operative treatment). Fifty-one had completely neoadjuvant treatment and received surgery. Pathological response was TRG 0/ 1/ 2/ 3 in 10/ 6/ 21/ 14 patients with pCR seen in 10 (19.6%). Major pathologic response (TRG 0 and 1) was seen in 16 (31.4%) patients. At 36.6 (17.6-57.8) months follow up, the median disease-free survival (DFS) and overall survival (OS) were not reached for all patients. DFS rate at 1, 2, and 3 year is 78.4%, 56.9%, and 54.3%. OS rate at 1, 2, and 3 year is 94.1%, 69.5%, and 65.2%. Compared with TRG 2 or 3, patients with MPR showed significant longer survival (p = 0.01). Twenty-four patients underwent immune microenvironment analysis on their pre-treatment specimens by multiplex immunohistochemisty. Compared with TRG 2 or 3 (n = 11), NK cells with positive CD56 expression in tumor parenchyma microenvironment in patients with MPR (n = 13) were significant decreased (p = 0.024). Conclusions: Perioperative toripalimab in combination with FLOT showed promising efficacy with high pCR and MPR rate in patients with resectable gastric/GEJ adenocarcinoma. MPR rate and NK cells in tumor microenvironment have a predictive on therapeutic efficacy, with deserves further study. Clinical trial information: NCT04354662 .
Prediction of brain metastases of breast cancer using next generation sequencing genomics.
Authors: John Hunting, Sean Ormond, Yuezhu Wang, Liang Liu, Fei Xing, Michael D. Chan, Jimmy Ruiz
Journal: Journal of Clinical Oncology (2024)

e14004 Background: Breast cancer was the most common malignancy diagnosed in 2023 with over 300,000 new diagnoses. Though it is highly treatable when caught in early stages, metastatic disease is highly morbid. Approximately 0.4% of all cases and 7.2% of cases of metastatic breast cancer will develop brain metastases. Hormonal receptors correlate poorly with risk of brain metastasis. Predictive factors for breast cancer brain metastases remain elusive. This project aimed to identify genomic risk factors for the metastasis of breast cancer to the brain. Methods: We created a retrospective cohort of all breast cancer patients with next generation sequencing (NGS) at a comprehensive cancer center and its associated clinics. All NGS in the cohort was performed by FoundationOne. Brain metastases were defined via ICD-10 codes. Univariate analysis was performed using Fisher’s Exact test. Significance was defined as p&lt;0.05 after adjustment of multiple testing corrections performed using the Benjamini-Hockberg procedure. A multivariable logistic regression model was fit; to avoid overfitting, the maximum number of covariables was defined by requiring 10 cases for every variable included. Model fit was compared by the Akaike information criterion (AIC) statistic. SAS v9.4 was used for all analyses. Results: This final cohort included 242 patients, of which 29 (12%) developed brain metastases. Among the standard panel of 223 tested genes, 11 were significantly associated with brain metastases after multiple testing correction. Significant genes included: TP53, GATA3, PIK3CA, EP300, MSH3, NTRK1, BRCA1, CBFB, FGFR4, MAP2K2, and NOTCH2. TP53 was the most prevalent gene mutation amongst brain metastases patients. The gene was present in 79% (23/29) of all brain metastases cases and 96% (23/24) of patients with TP53 had brain metastasis. PIK3CA and GATA3 were the next most common in 10 (34%) and 6 (21%) cases respectively. In building predictive models, the optimal model included TP53, GATA3, and CBFB which presented an AIC of 33.15 and an AUC of 0.98. The best two variable model included TP53 and PIK3CA with AIC of 49.67 and AUC of 0.95. Conclusions: Among this cohort, 11 genes were found to be significantly associated with the development of brain metastases. Among them, TP53 was the most prevalent while GATA3, PIK3CA, and CBFB also contributed to predictive ability. These variables suggest high levels of predictability, though given the limited sample thorough validation will be required. However, given the numerous genes found to be associated and the significant starting predictivity, there is potential for NGS to identify those at higher risk of brain metastases. Further study and expansion of NGS will be needed to validate these results and investigate the timing of brain metastases for the potential of early detection.
Beyond scalpels: A meta-analysis of robotic and laparoscopic gastrectomy in long-term oncological outcomes in gastric cancer.
Authors: Caroliny Silva, Larissa Hespanhol, João Pedro Oliveira, Isadora Mamede Mendes da Silva, Maysa Vilbert, Irami Araújo-Filho
Journal: Journal of Clinical Oncology (2024)

e16125 Background: Gastric cancer persists as a substantial worldwide health concern, serving as a prominent contributor to both the incidence and fatalities associated with cancer. In this context, robotic gastrectomy (RG) and laparoscopic gastrectomy (LG) in patients with gastric cancer is a subject of extensive scientific investigation, reflecting the ongoing evolution of minimally invasive surgical techniques. RG has been posited as a potentially advantageous alternative to LG, as it is associated with improved precision and maneuverability, particularly in complex anatomical scenarios. Conversely, LG, with its established history and widespread adoption, is characterized by a shorter learning curve and potential cost advantages. Scientific literature suggests comparable outcomes between the two techniques, while others report divergent results in terms of operative time, blood loss, and complication rates. However, the impact of both techniques in long-term oncological outcomes remains unclear. Therefore, we aimed to perform a systematic review and meta-analysis for RG and LG for oncological outcomes in patients with gastric cancer. Methods: A systematic search was performed in PubMed, Cochrane and Embase in January 2024 for randomized controlled trials or observational studies comparing RG with LG in patients with gastric cancer. Risk ratios (RR) for binary outcomes with a 95% confidence interval (CI) were pooled and a p-value &lt; 0.05 was considered statistically significant. Rayyan and Review Manager 5.3 software were selected, respectively, to manage the reported references and perform the statistical analysis of this study. Results: A total of 3727 results were screened, of which 13 were included in the meta-analysis, totalizing 25428 patients. There were no differences between RG and LG for 3-year overall survival (RR 1.03, 95% CI 1.00 - 1.06, I2 = 50%, p = 0.06), 3-year disease free survival (RR 1.01, 95% CI 0.95 - 1.06, I2 = 45%, p = 0.82), recurrence free survival (RR 0.51, 95% CI 0.22 - 1.20, I2 = 100%, p = 0.12), 5-year disease free survival (RR 1.02, 95% CI 0.99 - 1.05, I2 = 0%, p = 0.23), and ≥ 3-year overall survival (RR 1.02, 95% CI 1.00 - 1.05, I2 = 38%, p = 0.03). Conclusions: These findings from this comprehensive meta-analysis reveal a lack of discernible disparity between RG and LG in terms of oncological outcomes. The collective evidence suggests comparable results, emphasizing the need for continued research to refine our understanding and guide clinical decision-making in the pursuit of optimized patient care. These results contribute to the ongoing dialogue surrounding optimal treatment strategies for the assessed condition.
Intervention to improve care delivery and patient self-management for people with primary liver cancer who have socioeconomic disadvantages.
Authors: Christine B. Weldon, Jonathan Mizrahi, George Therapondos, Lingling Du, Carol Palmer, Amanda Medina, Tyler Sandow, Juan Gimenez, Ari Cohen, Michelle O'Brien, Sarika Ogale, Amie Tan, Julia R. Trosman
Journal: Journal of Clinical Oncology (2024)

e16232 Background: The 4R Oncology Model (4R = Right information/care/patient/time) supports patient self-management (Trosman, JCOOP 2021) and guideline-based care delivery (Liu, JCOOP 2022). 4R Care Sequence plans provide a care checklist and a graphical depiction of care timing and sequence. Here we report the impact of the 4R Care Sequence plans on care delivery and patient self-management among patients with primary liver cancer with socioeconomic disadvantages. Methods: 4R plans were provided to patients with liver cancer Jan – Dec ’23 (4R cohort). Patient-reported data were collected via surveys. Analyses compared the 4R cohort (N = 42) to a control cohort of patients who received care pre-4R, Jan - Dec ’22 (N = 52). Statistical analysis used Fisher’s exact and t-tests. Results: Survey response rates: control cohort 61% (52/85), 4R cohort 58% (42/73). Comparing control to 4R cohort respectively, patients exhibited the following characteristics: male (63%, 67%), White (67%, 74%), Black (25%, 19%), an average age (64.1, 63.9), and the majority had annual income less than $30,000 (62%, 67%). 4R significantly improved care delivery and patient self-management in all metrics vs control (Table). Patient rating of provider satisfaction on a 10-point scale was lower in the control cohort compared to the 4R cohort (8.4, 9.8, p &lt; 0.0001), data not shown. The significant improvement across metrics was observed regardless of age, race, sex. Among patients who made &lt; $30k annually, referral rates to a dentist before treatment increased significantly between control and 4R cohorts (19%,79%, p &lt; 0.0001). Among patients who made &gt; $30k annually, dental referral rates did not change between the control and 4R cohorts (70%, 71%, p = 1.00). Income was not a factor for other metrics. Conclusions: The 4R intervention using Care Sequence plans for patients with primary liver cancer facilitated improvements in care delivery and patient self-management regardless of age, race, sex or income. Our results indicate that 4R benefits all patients, including those with socioeconomic disadvantages. [Table: see text]
Immunotherapy responses in viral hepatitis-induced hepatocellular carcinoma: A meta-analysis.
Authors: Junaid Anwar, Hafiz Muhammad Arslan, Zouina Sarfraz, Ahmed Abdelhakeem, Maha Zafar, Anwaar Saeed
Journal: Journal of Clinical Oncology (2024)

e16223 Background: The advent of immunotherapy has ushered in a paradigm shift in the management of advanced hepatocellular carcinoma (HCC). The distinctive etiological profiles of HCC, characterized by HBV predominance in Asia and HCV/nonviral prevalence in the West, may impart intricacies in the immunological milieu, thereby influencing treatment outcomes. This meta analysis delves into the immunotherapeutic outcomes in patients with hepatitis-induced HCC. Methods: A systematic search was conducted by applying the Boolean logic (and/or) in PubMed (MEDLINE), Embase and Cochrane Library until February 3, 2024. This study investigates the outcomes of patients with HCC complicated by hepatic infection, focusing on overall survival (OS) and progression-free survival (PFS). A meta-analysis was conducted, combining data from 6 studies for OS and 5 studies for PFS. Statistical analyses were conducted using R (v.4.3.2., Vienna). Results: A total of 6 clinical trials pooling in 2958 patients were included in this meta analysis. For OS, the random effects model estimated the cumulative survival across the studies to be 18.3950 months (95% CI [16.3869; 20.4032]). Quantifying heterogeneity revealed a tau-squared value of 5.1789 and Higgins I-squared of 72.7% [41.2%; 87.3%]. The test of heterogeneity indicated significant variability among the studies (Q = 21.99, df = 6, p = 0.0012). For PFS, the random effects model estimated the combined progression-free survival to be 5.9906 months (95% CI [4.2889; 7.6923]). Quantifying heterogeneity revealed a tau-squared value of 3.4995 and Higgins I-squared of 95.4% [91.9%; 97.4%]. The test of heterogeneity indicated significant variability among the studies (Q = 87.66, df = 4, p &lt; 0.0001). Conclusions: The intricate relationship between HCC, hepatic infection, and treatment outcomes necessitates tailored therapeutic strategies for this patient population. Unveiling the heterogeneity in our analysis prompts a comprehensive exploration of potential factors, spanning both biological variances and clinical parameters. This inquiry fuels scientific discourse, urging an in-depth investigation into the immunological nuances influencing therapeutic responses in hepatitis-induced HCC. By addressing these complexities, we can optimize patient care and advance our understanding of effective treatment modalities for this challenging disease.