tbuckley/cabot-search huggingface dataset:
Nonionizing diagnostic imaging modalities for visualizing health and pathology of periodontal and peri‐implant tissues
Authors: Andy Wai Kan Yeung, Abeer AlHadidi, Rutvi Vyas, Michael M. Bornstein, Hiroshi Watanabe, Ray Tanaka
Journal: Periodontology 2000 (2024)

Radiographic examination has been an essential part of the diagnostic workflow in periodontology and implant dentistry. However, radiographic examination unavoidably involves ionizing radiation and its associated risks. Clinicians and researchers have invested considerable efforts in assessing the feasibility and capability of utilizing nonionizing imaging modalities to replace traditional radiographic imaging. Two such modalities have been extensively evaluated in clinical settings, namely, ultrasonography (USG) and magnetic resonance imaging (MRI). Another modality, optical coherence tomography (OCT), has been under investigation more recently. This review aims to provide an overview of the literature and summarize the usage of USG, MRI, and OCT in evaluating health and pathology of periodontal and peri-implant tissues. Clinical studies have shown that USG could accurately measure gingival height and crestal bone level, and classify furcation involvement. Due to physical constraints, USG may be more applicable to the buccal surfaces of the dentition even with an intra-oral probe. Clinical studies have also shown that MRI could visualize the degree of soft-tissue inflammation and osseous edema, the extent of bone loss at furcation involvement sites, and periodontal bone level. However, there was a lack of clinical studies on the evaluation of peri-implant tissues by MRI. Moreover, an MRI machine is very expensive, occupies much space, and requires more time than cone-beam computed tomography (CBCT) or intraoral radiographs to complete a scan. The feasibility of OCT to evaluate periodontal and peri-implant tissues remains to be elucidated, as there are only preclinical studies at the moment. A major shortcoming of OCT is that it may not reach the bottom of the periodontal pocket, particularly for inflammatory conditions, due to the absorption of near-infrared light by hemoglobin. Until future technological breakthroughs finally overcome the limitations of USG, MRI and OCT, the practical imaging modalities for routine diagnostics of periodontal and peri-implant tissues remain to be plain radiographs and CBCTs.
Radiographic assessment of the peri‐implant site
Authors: Philipp Sahrmann, Sebastian Kühl, Dorothea Dagassan‐Berndt, Michael M. Bornstein, Nicola U. Zitzmann
Journal: Periodontology 2000 (2024)

While peri-implant mucositis relies solely on clinical parameters, radiological assessment becomes indispensable for diagnosing peri-implantitis. Intraoral radiography, with its simplicity of application, low radiation exposure, and adequate representation of peri-implant structures, stands out as the standard of care for both immediate and follow-up assessments. Standardization by custom-made radiologic splints allows for excellent comparability with previous images and allows for the determination of even small changes in contour and density of the peri-implant bone. Furthermore, other radiographic modalities like panoramic radiography and cone beam computed tomography (CBCT) may provide useful features for specific patients and clinical cases while also showing innate limitations. Beyond the assessment of the marginal peri-implant bone level as the crucial parameter of clinical relevance, radiologic assessment may reveal various other findings related to the prosthetic restoration itself, the precision of its fit to the implant, and the peri-implant soft and hard tissues. Since such findings can be crucial for the assessment of peri-implant health and the implants' prognosis, a systematic diagnostic evaluation pathway for a thorough assessment is recommended to extract all relevant information from radiologic imaging. This article also provides an overview of the clinical and chronological indications for different imaging modalities in peri-implant issues.
Benchmarking computational variant effect predictors by their ability to infer human traits
Authors: Daniel R. Tabet, Da Kuang, Megan C. Lancaster, Roujia Li, Karen Liu, Jochen Weile, Atina G. Coté, Yingzhou Wu, Robert A. Hegele, Dan M. Roden, Frederick P. Roth
Journal: Genome biology (2024)

Abstract Background Computational variant effect predictors offer a scalable and increasingly reliable means of interpreting human genetic variation, but concerns of circularity and bias have limited previous methods for evaluating and comparing predictors. Population-level cohorts of genotyped and phenotyped participants that have not been used in predictor training can facilitate an unbiased benchmarking of available methods. Using a curated set of human gene-trait associations with a reported rare-variant burden association, we evaluate the correlations of 24 computational variant effect predictors with associated human traits in the UK Biobank and All of Us cohorts. Results AlphaMissense outperformed all other predictors in inferring human traits based on rare missense variants in UK Biobank and All of Us participants. The overall rankings of computational variant effect predictors in these two cohorts showed a significant positive correlation. Conclusion We describe a method to assess computational variant effect predictors that sidesteps the limitations of previous evaluations. This approach is generalizable to future predictors and could continue to inform predictor choice for personal and clinical genetics.
Immunotherapy plus chemotherapy versus chemotherapy alone in perioperative treatment for locally advanced gastric cancer: A systematic review and meta-analysis.
Authors: Isadora Mamede Mendes da Silva, João Pedro Oliveira, Melissa Maia, Caio Dabbous de Liz, Audrey Cabral Ferreira de Oliveira, Ana Caroline Fonseca Alves
Journal: Journal of Clinical Oncology (2024)

e16083 Background: The standard care for locally advanced gastric (LAGC) or gastroesophageal junction (GEJ) cancer is perioperative chemotherapy (CTX) with surgery. The therapeutic landscape has evolved with PD-1 and PD-L1 inhibitors, showing promise in advanced or metastatic disease. Investigating their role in locally advanced disease is an active research area. In response, we conducted a meta-analysis to evaluate the effectiveness of perioperative immunotherapy with CTX in LAGC/GEJ patients. Methods: We systematically searched PubMed, Embase, and Cochrane for randomized controlled trials (RCTs) comparing perioperative PD-1 and PD-L1 inhibitors in combination with CTX versus CTX alone for LAGC/GEJ. Evaluated outcomes included pathological complete response (pCR), R0 resection rate, downstaging rate, and treatment-related adverse events (TRAE) with a grade ≥ 3. Heterogeneity was assessed using I 2 statistics, employing a random-effects model for analysis. Statistical analyses were performed using R software version 4.3.2. Results: Among 2,452 patients from six RCTs, 1,228 (50.08%) received immunotherapy. Combining immunotherapy with CTX showed substantial improvements in pCR (RR 2.83; 95% CI 1.78-4.50; p &lt; 0.001). This effect persisted in the FLOT CTX subgroup (RR 2.15; 95% CI 1.37-3.38; p &lt; 0.001). Additionally, downstaging outcomes were superior in the immunotherapy group, with ypT0 (RR 1.96; 95% CI 1.50-2.55; p &lt; 0.001) and ypN0 (RR 1.36; 95% CI 1.19-1.54; p &lt; 0.001). However, no significant differences were observed in the R0 resection rate (RR 1.01; 95% CI 0.98-1.04; p = 0.603) and TRAE grade 3 or higher (RR 1.05; 95% CI 0.98-1.13; p = 0.177). Conclusions: These findings emphasize the effectiveness of combining PD-1 and PD-L1 inhibitors with CTX, indicating an improved pathological response compared to CTX alone. As expected, these positive outcomes persisted in the FLOT regimen. Our results provide evidence supporting the combination of immunotherapy and CTX as a perioperative treatment option for LAGC/GEJ patients.
Homologous recombination deficiency score served as an independent prognosis factor in esophageal squamous cell carcinoma.
Authors: Yulu Wang, Bowen Ding, Yunlan Tao, Lingli Huang, Qian Zhu, Chengying Gao, Mingli Feng, Yuchen Han
Journal: Journal of Clinical Oncology (2024)

e16080 Background: Homologous recombination deficiency (HRD) is a functional impairment of the homologous recombination repair (HRR) pathway, pivotal for mending DNA double-strand breaks, contributing significantly to cancer-associated genomic instability. While BRCA mutations traditionally underlie HRR defects, recent studies highlight varied responses to poly (ADP-ribose) polymerase (PARP) inhibitors based on specific HRR-related gene alterations. Despite HRD's relevance in various cancers, its role in esophageal squamous cell carcinoma (ESCC) remains underexplored. Methods: We conducted a retrospective analysis of HRD scores in 96 ESCC patients, assessing correlations with clinical characteristics and survival outcomes. Genomic sequencing was performed using a customized superHRD NGS panel. HRD scores were calculated based on 54,000 single-nucleotide polymorphisms, employing Kruskal-Wallis ranksum tests and two cut-off points for quantitative analysis. Kaplan-Meier survival and Cox regression model were employed to evaluate disease-free survival (DFS) and overall survival (OS). Results: Higher HRD scores correlated with advanced tumor stages, recurrence, and specific gene mutations ( TP53 and ABCB1). APC mutations were associated with lower HRD scores. Patients with high HRD scores demonstrated significantly shorter disease-free survival (DFS) and a trend towards shorter overall survival (OS), especially those who did not receive adjuvant therapy, emphasizing HRD's prognostic value. Conversely, HRD-high patients undergoing adjuvant therapy showed a tendency towards extended OS. Multivariate analysis identified HRD as an independent prognostic factor (HR = 2.814 for recurrence, HR = 1.772 for death). Validation with The Cancer Genome Atlas (TCGA) ESCC dataset supported our findings. Conclusions: This study unveils associations between HRD scores, clinical characteristics, and genomic mutations in ESCC, emphasizing HRD's potential as a prognostic biomarker. HRD assessment may aid in patient stratification and personalized treatment strategies. Future investigations should explore underlying molecular mechanisms and therapeutic implications of HRD-associated pathways in ESCC management.
Life expectancy of patients with early gastric cancer who underwent curative gastrectomy: Comparison with the general population using the Korean Statistical Information Service database.
Authors: ChangSeok Ko
Journal: Journal of Clinical Oncology (2024)

e16077 Background: Although clinical trials have reported the long-term survival of patients with early gastric cancer, data comparing their life expectancy with that of the general population is scarce. Our study estimated these patients’ life expectancy and analyzed the differences in life expectancy between patients with early gastric cancer and the general population. Methods: We enrolled patients who underwent curative gastrectomy and were diagnosed with pathologic stage 1 gastric cancer at Asan Medical Center from the gastric cancer registry. We determined patients’ survival status through the national health insurance system. Their life expectancy was analyzed and compared with that of the general population, utilizing data from the Korean Statistical Information Service database. Results: This cohort comprised 8,637 patients and 64.7% were men. Approximately 17.3% of participants were aged 70 years and older. Approximately 20% of patients underwent total gastrectomy. Life expectancy was favorable among women. Across all age groups, women’s life expectancy generally exceeded 80 years. Male patients showed a reduced life expectancy, typically 4-10 years shorter than their female counterparts. The average life expectancy of male patients aged over 80 years who underwent total gastrectomy was about 5 years, whereas that of their female counterparts was approximately 7 years. Female patients undergoing distal gastrectomy did not demonstrate a statistically significant variance in life expectancy compared to the general population. Conclusions: This study provided comprehensive life expectancy data, organized by age, sex, and type of gastrectomy in a large stage 1 gastric cancer cohort. Elderly patients undergoing total gastrectomy with limited life expectancy may benefit from considering alternative treatment options instead of total gastrectomy.
Camrelizumab combined with apatinib as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: A phase 2 trial.
Authors: Xiangrui Meng, Yu Qi, Zhengzheng Shan, Yang Yang, Qingxia Fan, Feng Wang
Journal: Journal of Clinical Oncology (2024)

e16087 Background: Increasing evidences prove the encouraging efficacy of neoadjuvant immunochemotherapy for esophageal squamous cell carcinoma (ESCC). However, the safety of chemotherapy is still unsatisfactory. Previous studies have confirmed the good efficacy and tolerance of PD-1 inhibitors combined with angiogenesis inhibitors in advanced ESCC. This trial is to assess the effectiveness and safety of camrelizumab (PD-1 inhibitor) plus chemotherapy or apatinib (angiogenesis inhibitor) as neoadjuvant therapy for locally advanced ESCC. Methods: This was an open-label, non-randomized phase 2 trial of patients with stage cT2-4aN0-3M0 ESCC. Eligible patients were 18-75 years old, had ECOG PS score of 0-1. Patients received 2 cycles (1 cycle per 4 weeks) of camrelizumab (200 mg Q2W) and apatinib (250 mg QD). Surgery was performed within 4-6 weeks after neoadjuvant therapy. The primary endpoint was major pathological response (MPR) rate. Secondary endpoints included pathological complete response (pCR) rate, R0 resection rate, disease-free survival (DFS), overall survival (OS), and safety. Results: Between Feb 2022 and Dec 2023, 24 patients (19 males and 5 females) with a median age of 67 years were enrolled in the study. Twenty-one patients completed neoadjuvant therapy, the ORR was 50% and the DCR was 95%. Nineteen patients completed surgery and all patients (100%) reached R0 resection, 3 patients (3/19, 10.5%) reached pCR, 8 patients (8/19, 42.1%) reached MPR, and 13 patients (13/19, 68.4%) had TNM downstaging. The median follow-up was 11.9 months, and the median DFS had not yet reached. Any grade and grade ≥3 adverse events occurred in 87.5% and 8.3% of 24 patients, respectively. The most common AEs were increased alanine aminotransferase (8/24, 33.3%), increased alanine aminotransferase (7/24, 29.2%) and thrombocytopenia(7/24, 29.2%). No new safety signals or treatment-related deaths were observed. Conclusions: Neoadjuvant camrelizumab in combination with apatinib in patients with locally advanced ESCC showed promising pathological response and downstaging effect with acceptable security. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT03917966 .
Neoadjuvant nivolumab plus paclitaxel/cisplatin- chemo-radiotherapy (neo-NTP-CRT) followed by esophagectomy for locally advanced esophageal squamous cell carcinoma (ESCC): A phase II study.
Authors: Ta-Chen Huang, Jhe-Cyuan Guo, Chia-Chi Lin, Hung-Yang Kuo, Chien Huai Chuang, Jason, Chia-Hsien Cheng, Feng-Ming Hsu, Jang-Ming Lee, Pei-Ming Huang, Kuan-Yin Ko, Chih-Hung Hsu
Journal: Journal of Clinical Oncology (2024)

e16098 Background: Adjuvant nivolumab has shown efficacy in reducing recurrence in patients (pts) with locoregional esophageal cancer harboring pathologic residual disease following neoadjuvant chemoradiotherapy (CRT). However, the efficacy of adding nivolumab to neoadjuvant CRT remains unclear. Methods: We conducted a phase II trial of neoadjuvant nivolumab (240mg IV on D-14, 1, 15, 29), paclitaxel (50mg/m 2 IV on D1, 8, 15, 22, 29), cisplatin (30mg/m 2 IV on D1, 8, 15, 22, 29) and RT (45Gy given in 25 fractions) followed by esophagectomy 6 to 8 weeks after finishing CRT in pts with locally advanced ESCC, defined as clinical stage cT3-4aN0M0 or cT1-3N1-3M0 according to the AJCC Cancer Staging System 8 th ed. (ClinicalTrials.gov Identifier: NCT05130684). The study, in a Simon’s two-stage design, used pathological complete response (pCR) rate as the primary endpoint. Secondary endpoints included feasibility, safety, recurrence free survival (RFS), progression free survival (PFS), and overall survival (OS). Results: Between Jan 2021 and Apr 2023, we enrolled a total of 17 pts. Fifteen were male. The median age was 52 years (range: 44~69). The clinical stage was I, II, and III in 1, 1, and 15 pts, respectively. All pts received neo-NTP-CRT with the following dose-intensities (mean dose intensity [range]): nivolumab (95% [50%~ 100%]), paclitaxel (75% [48%~ 100%], cisplatin (97% [80%~ 100%]), and radiotherapy (100%). Fourteen pts received esophagectomy, and 4 of them achieved pCR (24%). Because pCR for the first stage did not meet the efficacy criteria to move forward to second-stage, the enrollment was discontinued after enrolling 17 pts. During neo-NTP-CRT, the most common treatment-related adverse events (TRAEs) were leukopenia (76%), neutropenia (59%), thrombocytopenia (35%), and skin rash (35%); and the most common grade 3 and 4 TRAEs were leukopenia (24%), neutropenia (6%), and nausea and vomiting (6%). Among 14 pts receiving esophagectomy, 4 experienced surgical complications, including 2 with anastomotic leakage, 1 with subclavian artery rupture, and 1 with pneumonitis; one pt died 263 days after surgery, followed by a prolonged hospital stay due to refractory anastomotic leakage, infectious complications, and tumor progression. The median follow-up duration was 18 months. Median RFS, PFS and OS was 8, 12, and 16 months, respectively. Conclusions: Our data indicate that adding nivolumab to neoadjuvant paclitaxel and cisplatin-based CRT is feasible but does not improve pCR rate in locally advanced ESCC pts. Clinical trial information: NCT05130684 .
Tislelizumab combined with chemotherapy or radiotherapy as neoadjuvant therapy for resectable esophageal squamous cell carcinoma (TINES): A randomized, open, phase II study.
Authors: Yong Zhang, Shaomin Che, Nanzheng Chen, Xinju Li, Junke Fu, Chenao Yu, Tianren Wang, Runjia Liang, Haozhen Xu, Qifei Wu, Zhuoqi Jia, Cailin Zhu, Tuotuo Gong, Haijun Li, Boxiang Zhang, Yunyun Hu, Yaqi Liu
Journal: Journal of Clinical Oncology (2024)

e16090 Background: Although immunotherapy combined with chemotherapy has gradually been confirmed to improve the resectable esophageal squamous cell carcinoma (ESCC), it is necessary to explore other safe and efficient combination regimens. Radiotherapy could induce immunosensitization to improve the efficacy of PD-1 blocker, this study evaluated the efficacy and safety of tislelizumab combined with radiotherapy in resectable ESCC. Methods: 32 treatment-naïve patients with resectable ESCC (T 2-4a N any M 0 ) were planed and randomized (1:1) to two arms for neoadjuvant therapy. Arm A received tislelizumab (200 mg on day 1), paclitaxel (150 mg/m 2 on day 1) and cisplatin (75 mg/m 2 on day 1) once every 3 weeks for 3 cycles, and arm B received radiotherapy with 41.4 Gy in 23 fractions combined with 3 cycles (200 mg, Q3W) of tislelizumab. Surgery was planned in 4-6 weeks post neoadjuvant therapy. Postoperative adjuvant tislelizumab was given to arms A and B for up to 14 cycles. The primary endpoint was pathological complete response (pCR) rate. The secondary endpoints included major pathological response (MPR) rate, disease-free survival, overall survival and safety. Results: Between October 2022 to January 2024, 22 patients were enrolled: arm A (n = 12) and arm B (n = 10). 15 patients were male and 7 patients were female. The median age was 65 years (range, 37 to 75 years). 8 patients were in stage II, 13 were in stage III and 1 was in stage IV. 18 (81.8%) patients from arms A and B completed neoadjuvant therapy, and 10 patients underwent surgery, 6 patients were awaiting preoperative evaluation, still 2 surgery cancelations due to patient withdrawal for symptom improvement. The pCR rate was higher in arm B (25.0%, 1/4) compared to arm A (16.7%, 1/6). MPR rates were 83.3% and 75.0% for arms A and B. During neoadjuvant treatment, no grade 3-5 treatment-related adverse events were observed. Conclusions: Tislelizumab plus chemotherapy or radiotherapy as neoadjuvant therapy demonstrated encouraging therapeutic effect for resectable ESCC.
Association between homologous recombination deficiency (HRD) gene mutations and the efficacy of venadaparib in combination with irinotecan as third- or fourth-line treatment in patients with metastatic gastric cancer (mGC).
Authors: Min-Hee Ryu, Hyung-Don Kim, Do-Youn Oh, Keun-Wook Lee, Sun Young Rha, Seung Tae Kim, Won Sik Lee, Min Ju Hong, Myongjae Lee, Eun-Jihn Roh, Kyoung Soo Ha
Journal: Journal of Clinical Oncology (2024)

e16057 Background: Tumors with homologous recombination deficiency (HRD) have been suggested to be associated with a favorable response to poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitors. The aim of this exploratory analysis was to evaluate the association between the presence of HRD gene mutations and the efficacy of venadaparib, a novel PARP inhibitor, plus irinotecan in patients with mGC who had failed at least at least 2 lines of therapy. Methods: This was an exploratory analysis from a multi-national, phase 1b trial of venadaparib plus irinotecan in patients with mGC (NCT04725994). Tumor response was evaluated according to RECIST v. 1.1. Genomic analysis was conducted using ctDNA (GuardantOMNI Gene Panel version 1.0, Redwood City, CA) on Day 1 pre-dose. Results of the exploratory genomic analysis, which includes pathogenic or deleterious mutations of following genes: BRCA1/2, ATM, ATR, PALB2, RAD51, RAD51B/C/D, CHEK1/2, POLD1/2/3/4, BARD1, BRIP1, were analyzed with the efficacy outcomes. Results: In the dose-finding part of the clinical study, 26 patients were enrolled:13 had received two prior treatments and 13 had received three prior treatments, respectively. Of the 26 patients enrolled, 7 (26.9%) had mutations involved in HRD (4 with ATM, 1 with BRCA2, 1 with BARD1, and 1 with ATR mutations, respectively), and were treated with varying doses of venadaparib plus irinotecan. Among the 7 patients with a mutation in HRD genes, an objective response rate (ORR) was 57.1%, and median progression free survival (mPFS) was 5.6 months (95% confidence interval [CI] 1.2–not reached). For those without a mutation in HRD genes (n = 19), 1 patient achieved partial response and 13 achieved stable disease as best response with a mPFS of 4.0 (95% CI 2.9-5.5) months. Conclusions: Venadaparib in combination with irinotecan showed promising efficacy outcomes in patients with mGC, especially for those with mutations of HRD-related genes. Further development of this combination may consider a biomarker-based approach. Clinical trial information: NCT04725994 . [Table: see text]