tbuckley/cabot-search huggingface dataset:
Pyrotinib combined with SHR6390 in the treatment of refractory advanced HER2 positive gastric cancer or solid tumors: Safety and efficacy results from a phase Id trial.
Authors: Dan Liu, Yingying Xu, Jifang Gong, Fen Yang, Lin Shen, Huajun Li
Journal: Journal of Clinical Oncology (2021)

e16009 Background: Pyrotinib (an irreversible pan-ErbB inhibitor) combined with SHR6390 (a novel oral small molecule CDK4/6 inhibitor) had shown anti-tumor activity in pyrotinib-resistant PDX models. A phase Id trial was conducted to evaluate the safety and efficacy of pyrotinib combined with SHR6390 in the treatment of refractory advanced HER2 positive gastric cancer or solid tumors (NCT03480256). Methods: A standard “3+3” design was conducted in this trial. Patients (Pts) received pyrotinib (qd, d1-28; q4w) combined SHR6390(qd, d1-21; q4w) at dose of 400/100mg (cohort A), 320/100mg (cohort E) and 400/75mg (cohort F) until disease progression or intolerable toxicity. The primary endpoint was safety and maximum tolerated dose. Results: From Sep. 2019 to Dec. 2020, 19 pts (14 gastric cancer, 3 colorectal cancer, 2 other solid tumors) were enrolled (A: n = 6; E: n = 6; F: n = 7). 15 pts received and progressed on Herceptin before enrollment. In cohort A, one DLT was observed (Grade 4 neutropenia), and another 3 pts suffered G3 neutropenia, anemia or thrombocytopenia. Considered of safety, the dose levels were decreased and designed as cohort E and F. In cohort E, one DLT was observed (G4 neutropenia). No DLT was observed in cohort F. The most common hematologic toxicities were neutropenia (95%), anemia (74%) and thrombocytopenia (74%). The most common non-hematologic toxicities were diarrhea (53%), mucositis (26%) and nausea (21%). The most common G3/4 AEs were leukopenia (37%) and anemia (16%). No G3/4 non-hematologic toxicity was observed. 18 pts were included in efficacy analysis. The overall response rate was 38.9%, with 7 PR (A: n = 3; E: n = 2; F: n = 2) and 7 SD. The median PFS was 3.83 months, with 2 pts received treatment over 12 months (A: n = 1; F: n = 1). Conclusions: Pyrotinib combined with SHR6390 had shown acceptable safety profile and encouraging efficacy in refractory advanced HER2 positive solid tumors. Further study would be carried out at the dose in cohort A. Clinical trial information: NCT03480256.
Clinical outcomes, prognosis, and predictors of salvage surgery in oral cavity squamous cell carcinoma.
Authors: Wen-San Lan, Hsueh-Ju Lu, Yu-Wei Chiu, Chih-Yu Peng, Hsien-Chun Tseng, Chung-Han Hsin, Chun-Yi Chuang, Chun-Chia Chen, Wei-Shiou Huang, Sung-Fa Yang
Journal: Journal of Clinical Oncology (2021)

e18040 Background: Salvage surgery (SS) is one of the curative options for oral cavity squamous cell carcinoma (OCSCC) patients with locoregional recurrence (LRR) or secondary primary, but the role of SS should be reevaluated between life expectancy, morbidity, and quality of life. Selecting suitable OCSCC patients receiving SS is important. Methods: From 2010 to 2018, newly diagnosed OCSCC patients who progressed to LRR or secondary primary were recorded. Clinical outcomes, prognostic factors, and predictors were analyzed for the patients receiving SS. Cox regression analyses were performed for PSS, defined from the date of SS to the date of death or last follow-up. Survival was estimated using the Kaplan–Meier method and log-rank tests. Results: A total of 263 newly diagnosed OCSCC patients progressing to LRR or secondary primary were recorded. Half (55.1%, 145/263) of them received SS, and one-third (29.7%, 43/145) of the SS group received twice and more times SS. Median survivals after disease progression were 65.6 and 10.6 months for patients with or without SS, respectively (P &lt; 0.001). A total of 214 SS events were enrolled for analysis. Nearly twenty percentage (20.1%, 39/194) of SS events would progress to death within 1 year after surgery (PSS &lt; 1 year). PSSs of the first, secondary, third, and fourth or more times SS were 64.2, 47.6, 40.9, and 18.9 months, respectively (P = 0.217). Surgical features of the last surgery (perineural invasion and depth of invasion), the interval between the last and current surgery, and clinical N staging of the current surgery were the four independent factors for PSS. To predict the patients with PSS &lt; 1 year, a scoring system was established that each of the independent factors was scored one point. The area under the curve of the scoring system was 0.755, and sensitivity, specificity, positive predictive value, and negative predictive value were 66.7%, 76.0%, 39.0%, and 90.8%, respectively (Table). Conclusions: A scoring system with a high negative predictive value was established to predict PSS &lt; 1 year.[Table: see text]
Advanced tumor progression detection by leveraging EHR based convolutional neural network boosting approaches.
Authors: Guanhao Wei, Li Zhou, Lynn L Lu, Robert G Steen
Journal: Journal of Clinical Oncology (2021)

e13581 Background: Medical research in the areas of immunotherapies and targeted therapies has been drawing heavy attention and investment as the number of approved therapies continue to rise. Advanced findings on cancer treatment based on rich healthcare records help doctors to understand patient’s characteristics. The more accurate one can make a mathematical model predicting the likelihood of disease appearance, progression or treatment initiation, the better a proactive and effective targeting solution can be provided. Methods: Create positive/negative labels for patients who start to receive treatment or not within a time-sensitive window. Based on EHR records as Procedures, Prescription, and Diagnosis (PPD), patient’s feature interrelationship can be determined by a conditional probability matrix. Map PPD data to a well-designed patient-image profiles based a modified genetic algorithm to optimize and measure closeness. A Convolutional Neural Networks (CNN) model is then used to extract characteristics from patients’ feature image and learn the local patterns. Training the CNN model together with other upgraded AIML models is used to enhance overall prediction precision. Results: 144 different aggregated PPD features for patients with Chronic Lymphocytic Leukemia (CLL) were selected from the databases. Overall, the number of positive patients, who received treatment due to disease progression, is around 3% among 60K cases in each cohort, which is an extremely unbalanced dataset that is a challenge task for model training. In practice, we care about the model precision at k, which is the percentage of truly identified patients with k highest prediction scores. Comparing to common machine models like Random Forest, XGBoost and CatBoost, our proposed CNN model boosts the ensemble of baseline model performance in terms of average prediction precision at 1000 from 14.9% to 17.1%, which is about 15% relative percentage increase. Using this approach, many more truly identified patients could potentially receive targeted treatment on time. Patients’ top features and key feature interactions can also be identified as important references. Conclusions: The novel CNN boosting algorithm considers both aggregated PPD feature pairs using the graphical structure, significantly improves prediction model performance, and increases the model interpretability. In summary, the proposed model can help identify more potential patient candidates and determine precise treatment options.
Overall survival after perioperative chemotherapy in the management of pulmonary metastasis in osteosarcoma.
Authors: Zeba Siddiqui, Megan E Delisle, Amirrtha Srikanthan, Ying Wang
Journal: Journal of Clinical Oncology (2021)

e23508 Background: Pulmonary metastasectomy is performed on a select cohort of patients with advanced osteosarcoma with the potential for long term survival. However, evidence on peri-operative chemotherapy at time of metastasectomy is not completely understood and difficult to summarize without a systematic examination of existing literature. The purpose of this project is to perform a meta-analysis of existing studies to determine overall survival (OS) and prognostic factors in adults and children with advanced and recurrent osteosarcoma receiving chemotherapy around time of metastasectomy. Methods: We reviewed survival studies conducted in children and adults with advanced and recurrent osteosarcoma who undergo pulmonary metastasectomy published in English with more than 5 patients. The primary outcome was overall survival. Literature searches were performed in multiple electronic databases including Ovid MEDLINE (1946 to present), Ovid EMBASE (1974 to present), Web of Science, and Cochrane Library. Two investigators independently screened all citations, abstracts, and full-text articles. Results: 24 out of 80 observational studies between 1977 to 2018 were included. 2146 patients were studied of which 987 underwent pulmonary metastasectomy for osteosarcoma. 822 patients received perioperative chemotherapy in this setting. No randomized controlled trials were identified. Studies included patients from Asia, Africa, Europe, and North America. The median OS ranged between 20 to 90 months. 5-year OS ranged between 15 to 63%. Factors associated with survival included: age, number of lesions, disease free interval, time of development of metastases, number of lesions and laterality of pulmonary disease. Conclusions: Overall survival in study has a significant range. Factors influencing survival included intrinsic factors such as patient age and disease characteristics, as well as extrinsic factors such as evolution of chemotherapy regimen over the past four decades. The main limitations are related to the inherently low-quality evidence as a result of lack of randomized controlled trials. More comprehensive data is needed to guide shared decision making in this area.
Estimating the Cost Savings and Cost Effectiveness of Low Dose Immune Tolerance Induction (ITI) Therapy with Bypassing Agent Prophylaxis Compared to High Dose ITI and Low Dose ITI
Authors: Gili Kenet, Abiola Oladapo, Josh Epstein, Thompson Christin, Aaron Novack, Diane J. Nugent
Journal: Blood (2017)
SAT0727-HPR CHANGES IN ACHILLES TENDON STIFFNESS IN GOUT MEASURED BY ELASTOGRAPHY – A PRELIMINARY STUDY
Authors: Simon Otter, Catherine Payne, Anna-Marie Jones, Nick Webborn, Peter Watt
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> In addition to acute attacks of severe joint pain and swelling, chronic gout has been associated with weaker foot/leg muscles, altered gait patterns and on-going foot pain. Inflammation associated with gout may change tissue elasticity and ultrasound imaging (US) utilising elastography is a non-invasive method of quantifying these changes in tendon stiffness and elastography findings have not previously been reported in individuals with gout. <h3>Objectives</h3> To determine differences in Achilles tendon stiffness in people with chronic gout compared to controls (non gout) <h3>Methods</h3> A cross sectional study comparing people with gout according to 2015 ACR/EULAR criteria and age/sex matched controls. Clinical and demographic data were collated and US imaging used to determine tendon thickness, presence of gouty tophi and/or aggregates and levels of angiogenesis. Previously validated protocols for conventional US imaging [1] and shear wave elastography [2] were used. Prior to data collection, intra-observer error was good (ICC (2) 0.69 (95%CI 0.62-0.89)). Ten elastography measures were taken along a longitudinal section of the mid-point of the Achilles tendon bilaterally. Data were summarised using descriptive statistics and a repeated measures ANCOVA was used to compare elastography outcomes between the two groups for the left and right foot separately after accounting for Body Mass Index (BMI). <h3>Results</h3> A total of 14 people with gout and 13 age/sex matched control subjects participated. Table 1 displays clinical and demographic data. A small proportion of those with gout presented with intra-tendon aggregates and/or intra-tendon tophi in one or both tendons n=7 (27%) for both). There was no significant difference in tendon thickness between groups, neo-vascularity was present in n=3 (21%) gout participants. Elastography findings (table 2) demonstrated significantly reduced tendon stiffness in those with gout compared to controls. <h3>Conclusion</h3> Subjects with chronic gout show reduced Achilles tendon stiffness compared to controls. From a clinical standpoint, our findings were similar to elastography measurements in otherwise healthy subjects with Achilles tendinopathy and who did not have gout [3]. <h3>References</h3> [1] Carroll M, Dalbeth N, Allen B, et al. Ultrasound Characteristics of the Achilles Tendon in Tophaceous Gout: A Comparison with Age- and Sex-matched Controls. J Rheumatol. 2017 44(10):1487-1492. [2] Payne C, Watt P, Cercignani M, Webborn N. Reproducibility of shear wave elastography measures of the Achilles tendon. Skeletal Radiol. 2017 17 2846-8. [3] Payne C 2018 Clinical Applications of shear wave elastography to Achilles tendon imaging and monitoring of a rehabilitation protocol for Achilles tendonopathy PhD Thesis, University of Brighton <h3>Disclosure of Interests</h3> None declared
Olanzapine or dexamethasone, with 5-HT3 receptor antagonist and NK-1 receptor antagonist, to prevent nausea and vomiting induced by cisplatin-based doublet chemotherapy: A non-inferiority, prospective, multi-centered, randomized, controlled, phase III clinical trial.
Authors: Zhigang Liu, Yuling Zhou, Shuang Yang, Wei-neng Feng, Ming-Yuan Chen, Xiong Zou, Guang Han, Jie Tang, Guorong Zou, Yu-Xiang He, Lemeng Zhang, Lei Cui, Hualin Chen, Guo Li, Shan Jiang, Jin Gao, Lin Xiao, Qun Zhang, Wei Yi, Chenghui Huang
Journal: Journal of Clinical Oncology (2021)

TPS12133 Background: Chemotherapy-induced nausea and vomiting (CINV) is a common side effect of cancer treatments, and dexamethasone offers an advantage over placebo for protection against chemotherapy-induced emesis in both acute and delayed phases. However, its side effects are diverse including moderate to severe insomnia, hyperglycemia, dyspepsia and so on, which are gathering increasing concerns. What’s more, dexamethasone is not applicable to all cancer patients. The incidence of diabetes mellitus varies in different cancer which can reach up to 55.3%, and dexamethasone might not be a proper anti-emesis choice for them. Besides, dexamethasone delivery is always on debating when patients are receiving immunotherapy. However, all anti-emesis regimen recommended in guidelines are dexamethasone based. Alternative anti-emesis regimen are required. Studies have shown that olanzapine plays an important role in treating delayed, refractory, breakthrough nausea and vomiting. Thus, we initiated this prospective, multi-center, phase III study to validate the dexamethasone-free protocol: the non-inferiority role of applying olanzapine to prevent CINV instead of dexamethasone. Methods: This clinical trial started on February 3, 2020 is being conducted in 23 centres. All patients eligible are chemotherapy naïve and plan to receive cisplatin-containing regimen. Based on a 70% complete remission rate of previous study, to demonstrate a non-inferiority margin of 10%, 548 patients are required for two arms with the consideration of 5% of drop out and lost to follow-up (80% power,α = 0.05). Study design: Enrolled patients are randomized 1:1 into 2 arms to receive olanzapine or dexamethasone combined with 5-HT3 receptor antagonist (palonosetron, granisetron or ondansetron) and NK-1 receptor antagonist (aprepitant or fosaprepitant) from the first day of chemotherapy. Olanzapine (5mg) is delivered orally per night from day 1 to day 4. Dexamethasone (12 mg) is given orally or intravenously within 30 minutes before cisplatin administrated on day 1; on day 2-4, the orally or intravenously given dose of dexamethasone is 8 mg. The primary endpoint is complete remission rate of vomiting during the whole observation period (0-120 hours from the starting of first course chemotherapy delivery). The secondary endpoints are complete remission rate of vomiting during 25-120 hours from the starting of first course chemotherapy delivery and no nausea rate during the whole observation period. Besides, side effects will be recorded according protocol. Clinical trial information: NCT04437017.
Final report from a registry study of patients with active cancer undergoing ecological staging.
Authors: James R. Cunningham, Cheryl Dodd, Jon Rittenbach, Mitch Clemens
Journal: Journal of Clinical Oncology (2021)

e22501 Background: The host-cancer relationship can be viewed as a set of tumor supportive and inhibitory interactions, that is as an ecosystem. An advantage of such a perspective might include a more dynamic understanding of the selection pressures affecting tumor evolution. If so then a means of detecting and measuring those forces would be of help in understanding that drive and point to potential therapeutic clinical interventions. Towards this goal a registry study of patients with invasive cancer was conducted to examine readily available clinical measures to inform an ecological staging system. Methods: Eligibility for registry participation included age of 18 years or older, active cancer requiring treatment, life expectancy estimated to be at least six months and willingness to provide informed consent for this IRB-approved study. Ecological staging was then conducted at entry assessing 22 separate clinical parameters from history, physical exam and laboratory known to effect tumor biology, grouped into eight profiles and scored using a trichotomization of data, increasing score corresponding to an increase in positive tumor selection. To aggregate data from the profiles, a geometric figure, an octamer, or ecogram, was constructed, vertices representing the net score of each of the eight profiles. We hypothesize that the area bounded by the polygon, ecogram area (EA) would reflect an index of adverse, tumor-supporting ecological influence. Overall survival was determined from time of diagnosis of cancer until time of registry closure. Results: 15 subjects, eight female, seven male, ages 53-84 (median 64) participated in the registry. Complete ecological staging was obtained from all participating subjects, an indication of feasibility for collection of such data in the clinic. Resulting EA ranged 12-fold (0-12.1) across subjects suggesting sensitivity of EA to differences in selection pressures among the participants; ecogram morphology from individual subjects demonstrated unique shapes, an indication of specificity for character of individual tumor ecological landscape. Mean overall survival for participants from time of cancer diagnosis was 265 weeks. For 12 subjects with advanced stage disease, overall survival was inversely related to ecogram area (r = -.45). Conclusions: Ecological staging of cancer from clinical parameters proved feasible in this registry study of patients with active cancer. Ecological information from those parameters when aggregated using a geometric figure, an ecogram, demonstrated both sensitivity and specificity for differences among participants. For those subjects with advanced stage disease, ecogram area was inversely related to overall cancer survival. Ecological staging may be a useful tool in gauging selection pressures affecting cancer evolutionary tendency and of potential benefit to oncologists in forecasting such development.
Time intervals between U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) new cancer therapy approvals.
Authors: Mark Lythgoe, Jonathan Krell, Jeremy Lyle Warner, Aakash Desai, Ali Raza Khaki
Journal: Journal of Clinical Oncology (2021)

1575 Background: Novel therapies are transforming cancer care. Regulatory review and approval are essential to deliver safe and efficacious innovations to patients. Studies prior to 2010 describe quicker approval decisions for new oncology drug registrations with the FDA compared to the EMA (median delay 238 days). Both regulatory agencies have subsequently improved procedures to expedite approval times. We compared regulatory market authorisation dates at the FDA and EMA for new oncology therapies from 2010-2020. Methods: New oncology therapeutic approvals between 2010-2020 were identified from the FDA and EMA regulatory databases. We analysed only initial approvals (not supplementary licenses) for active anti-cancer therapies (excluding biosimilars and supportive drugs). The delay in regulatory approval between the FDA and EMA was calculated in calendar days. We further analysed therapies by therapeutic class, evaluating for significant differences. Results: We identified 108 new therapy registrations during the study period. 104 (96.3%) therapies were approved by the FDA and 90 (83.3%) had EMA market authorisation. 4 (3.7%) drugs were not FDA registered, including 3 unsuccessful applications and 1 which sought licensing in a different indication. 18 (16.5%) drugs were not EMA registered, including 9 (8.8%) which did not pursue EMA licensing, 3 (2.9%) withdrawn licensing applications, 3 (2.9%) sought licensing in different tumour group/indication, 1 (0.9%) rejected application and 2 (1.9%) with applications under review at submission date. Of the 86 drugs approved by both agencies, 80 were approved first by the FDA and 6 by the EMA. The median delay in approval between the FDA and EMA was 227 days (IQR:124-354 days). Table shows approvals by therapeutic class. The shortest median time difference for approval was for monoclonal antibodies (171 days) with the longest for kinase inhibitors (281 days). Conclusions: This study shows more new oncology therapies are approved by the FDA than the EMA. Patients in the US typically have access to approved therapies earlier than in Europe. From 2010 to 2020 the median delay between FDA and EMA approval was 227 days, falling by 11 days compared to 2003-10, [non-statistically significant]. Such lengthy delays could exceed the life expectancy of many patients with advanced cancer. Innovations for accelerated approval at both the FDA (e.g. Project Orbis) and EMA (e.g., PRIME) have potential to lead to faster approval.[Table: see text]
Hepatic Arteriovenous Malformation: The Search for a PTEN Mutation!
Authors: Léa Duhaut, Mélanie Eyries, Maïté Lewin, Oriana Ciacio, Ilias Kounis, Daniel Cherqui, Teresa Antonini, Jean‐Charles Duclos‐Vallée, Cyrille Feray, Didier Samuel, Catherine Guettier, Audrey Coilly
Journal: Hepatology (2021)

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