tbuckley/cabot-search huggingface dataset:
Nitroglycerin (NTG) plus whole intracranial radiotherapy for brain metastases (BM) in non-small cell cancer patient (NSCLC): A randomized open label, phase II clinical trial.
Authors: Oscar Gerardo Arrieta Rodriguez, Norma Hernández-Pedro, Federico Maldonado, Maritza Ramos, Masao Yamamoto-Ramos, Diego López, Francisco Lozano, Zyanya Lucía Zatarain-Barron, Graciela Cruz-Rico, Pedro Barrios-Bernal, Mario Orozco-Morales, Bernardo Cacho, Diana Flores-Estrada, Andres Felipe Cardona Zorrilla, Christian Diego Rolfo
Journal: Journal of Clinical Oncology (2021)

9114 Background: Hypoxia has been associated with chemo-radioresistance secondary to Vascular Endothelial Growth Factor Receptor induced by Hypoxia Induced Factor (HIF). Nitroglycerin (NTG) can reduce HIF-1 in cell lines, and this may have anti-angiogenic, pro-apoptotic, and anti-efflux effects. Particularly, EGFR mutated (EGFRm) tumor cell lines have been shown to overexpress both VEGF and HIF. In this phase II study, we evaluated the effect of transdermal NTG on intracranial objective response rate (iORR), intracranial progression-free survival (ICPFS), and overall survival (OS) of NSCLC patients with BM. Methods: We performed an open-label, phase II clinical trial among ninety-six histologically confirmed NSCLC patients with BM. Patients were randomized 1:1 to receive NTG plus WBRT (30 Gy in 10 fractions) or WBRT alone. iORR and ICPFS were evaluated by MRI by two independent, blinded radiologists. Nitroglycerin was administered using a transdermal 36 mg patch, which released 10 mg in 24 hours with a rest interval of 12 hours from Monday-Friday throughout WBRT administration (10 days). Results: Fifty patients were allocated to the control group, while 46 were allocated to the experimental group (NTG); among these 26 (55.3%) had EGFRm in the control group and 21 (44.7%) had EGFRm in the NTG arm. In terms of the iORR, patients in the NTG group had a significantly higher response when compared to controls (56.6% vs. 43.5%; p = 0.024). Additionally, patients who received NTG in addition to WBRT had an independently prolonged ICPFS compared with those who received WBRT alone (27.7 vs. 9.6; HR: 0.470 [95%CI: 0.24-0.89]; p = 0.021). PFS was also positively impacted (HR: 0.519 [95%CI: 0.27-0.98]; p = 0.043). The benefit in terms of iORR and ICPFS (HR: 0.38 [95%CI: 0.16-0.91]; p = 0.030) was particularly important in the EGFRm patient subgroup. No differences were observed in OS. A significantly higher rate of vomiting presented in the NTG arm of the study ( p= 0.016). Conclusions: The concurrent administration of NTG and chemo-radiotherapy improves iORR and ICPFS among NSCLC patients with BM. The benefit is particularly significant in the EGFRm patient subgroup. Clinical trial information: NCT04338867.
Correlation of Agent Orange exposure, cytogenetics, and clinical outcomes in multiple myeloma and MGUS.
Authors: Pruthali Kulkarni, Laurel Copeland, James Andy Hall, Jyothi Dodlapati
Journal: Journal of Clinical Oncology (2021)

e20008 Background: Multiple myeloma (MM) accounts for 1-2% of cancers worldwide. MM and monoclonal gammopathy of unknown significance (MGUS) are associated with Agent Orange exposure (AO) in Vietnam war veterans. Studies show poor outcomes in AO-exposed patients developing MM. No study has evaluated AO exposure and adverse cytogenetics in patients with MM. Methods: We reviewed patients with MGUS and/or MM in the Central Texas Veterans Health Administration system in 2010-2015 to evaluate AO exposure, adverse cytogenetics, transformation from MM to MGUS, and overall survival (OS). Inclusion criteria were active-duty military when AO was used (1961-1971). Presence of 17p13, t(4;14), t(14;16), t(14;20), or Gain 1q by FISH defined high-risk cytogenetics. Poor prognosis per serum free kappa/lambda ratio was defined as &lt; .03 or &gt; 32 K/L (high-risk). Regulatory review approval was obtained. Cox survival models generated hazard rate ratios and their 95% confidence intervals (HR) for AO status (AO, non-AO, undetermined), age, race/ethnicity, transformation, and FISH data. Results: Among 129 veterans, 30% were Black and 12% Hispanic (mean age 74.0 years, SD 6.9, range 59-97). MGUS was diagnosed in 44%, MM 74%, and transformation 19%. FISH abnormalities were rare thus AO association cannot be definitively stated; see table. A subsample with known AO and K/L (n = 81) showed no association: 69% high-risk had AO vs 76% moderate-risk; chi2 = 0.54; p = .46. In the adjusted model, Hispanic patients (HR = 3.3; 1.2-9.1) and those with high-risk cytogenetics (HR = 6.0; 1.1-34.1) had higher mortality; AO was unrelated. Conclusions: Although preliminary analyses find no associations of AO and transformation with OS, ethnicity and FISH abnormality associations are intriguing. Chart review is 50% complete. The paucity of cytogenetics data begs further examination, and continued study is merited to fully recognize what predisposes MM development following AO exposure.[Table: see text]
EMBR-11. SYNERGISTIC DRUG COMBINATIONS FOR THE TREATMENT OF <i>MYC</i> AMPLIFIED GROUP 3 MEDULLOBLASTOMA
Authors: Simon Zeuner, Johanna Vollmer, Heike Peterziel, Romain Sigaud, Sina Oppermann, Dina ElHarouni, Thomas Hielscher, Olaf Witt, Ina Oehme, Till Milde, Jonas Ecker
Journal: Neuro-Oncology (2021)

Abstract Background Medulloblastoma (MB) is a highly aggressive brain tumour in children. Patients with Group 3 MB harbouring a MYC-amplification (subtype II) show a particularly poor outcome despite high-intensity multimodal therapy. We and others have previously shown that MYC amplified Group 3 MB cells are highly susceptible towards treatment with class I histone deacetylase (HDAC) inhibitors such as entinostat. However, in clinical trials HDACi as a monotherapy show only modest efficacy in solid tumours. We propose to increase the efficacy of class I HDACi by drug combinations. Methods To identify synergistic drug combinations (entinostat + X) for the treatment of MYC amplified MB we performed a drug screen with a library of n=75 clinically available compounds as single agents and in combination with entinostat in n=3 MYC amplified vs. n=1 MYC-non amplified cell lines. Synergistic behaviour of the six most promising drug combinations was validated by metabolic activity assays, cell count experiments and gene expression profiling. Synergy was assessed by the Loewe additivity model using a combination of ray design and checkerboard matrix. Results The drug screen revealed n=20/75 drugs that were particularly effective (drug sensitivity score ≥10) in combination with entinostat treatment in all three MYC amplified cell lines. Synergy assessment of the top n=6 drugs confirmed strong synergistic activity with entinostat for n=2 drugs (navitoclax, irinotecan). The BCL-2 family inhibitor navitoclax showed the most robust synergy with entinostat in subsequent validation experiments. Conclusion Several drugs either clinically available or currently in clinical trials, including the BCL-2/Xl/w inhibitor navitoclax, show promising effects in a combination therapy with entinostat for the treatment of MYC amplified Group 3 MB.
Urinary exosomes-based Engineered Nanovectors for Homologously Targeted Chemo-Chemodynamic Prostate Cancer Therapy via abrogating EGFR/AKT/NF-kB/IkB signaling
Authors: Shaojun Pan, Yuhui Zhang, Mark Huang, Zhoufeng Deng, Amin Zhang, Lijia Pei, Lirui Wang, Weiyong Zhao, Lijun Ma, Qian Zhang, Daxiang Cui
Journal: Biomaterials (2021)
The feasibility of same day pegfilgrastim-cbqv administration in breast cancer patients receiving myelosuppressive chemotherapy regimens at a northern Virginia cancer center.
Authors: Maya Leiva, Angela Pennisi, Kathleen Kiernan Harnden, Patricia Conrad Rizzo, Lauren Ann Mauro
Journal: Journal of Clinical Oncology (2021)

e18687 Background: The long-acting injectable G-CSF, pegfilgrastim and its biosimilars have historically been given to patients 24 hours following the administration of myelosuppressive chemotherapy for either primary or secondary prophylaxis of febrile neutropenia (FN). Previous literature has indicated that pegfilgrastim administration prior to 24 hours post chemotherapy, may result in a deepened and prolonged neutropenia due to the increase in circulating granulocytes exposed to chemotherapy. With the onset of the COVID-19 pandemic and to reduce potential SAR-CoV-2 exposure to cancer patients on therapy, we implemented same day administration of injectable pegfilgrastim-cbqv among select breast cancer patients receiving myelosuppressive chemotherapy regimens from March 2020 – February 2021. Methods: Utilizing retrospective EHR chart reviews, 55 patients among 4 medical oncologists in our breast cancer group were identified as meeting the criteria of same day pegfilgrastim-cbqv administration. Inclusion was based on completion of at least 2 consecutive cycles of same day pegfilgrastim-cbqv 6 mg subcutaneous injection for primary or secondary prophylaxis. The selected patient charts were reviewed for the incidence and severity of FN. Among the patients who had documented FN, further subgroup analyses were done regarding baseline characteristics, timing of neutropenia, regimens, regimen sequence, and reported ADRs associated with pegfilgrastim-cbqv. Results: 9 (16.4%) of the 55 patients experienced FN (Grades 3-4) and 6 (10.9%) patients were hospitalized. There were no Grade 5 events and none had therapy discontinued due to FN. 8 (88.9%) of the patients experienced FN between cycles 1 and 2. Of note, there were no cases of COVID-19 among the 9 patients who had an episode of FN. 52 (94.5%) of the 55 patients received treatment with curative intent and 3 (5.5%) had metastatic disease on a subsequent line of therapy. The median age was 49.1 years (range 29-71) and patients were 56.4% Caucasian, 18.1% Black or African American, 12.7% Asian, and 12.7% Hispanic/Latina. Conclusions: Based on the retrospective data analysis, same day pegfilgrastim-cbqv appears to be a safe and effective option in the primary and secondary prophylaxis of FN with myelosuppressive standard of care chemotherapy used in breast cancer treatment. Though our review was limited by a relatively small sample size and confined to younger (49.1 median age) breast cancer patients, this opens the door to further re-evaluation of same day pegfilgrastim-cbqv administration in other patient populations. In a post pandemic treatment world, this slight change in practice has the potential to reduce patient financial toxicity associated with multiple medical visits, provide an alternative to on-body injector formulations, and ensure treatment adherence.
Clinical and Genetic Relevance of Somatic Mutations in Core Binding Factor (CBF) Acute Myeloid Leukemia (AML) Patients Using Serial Sequencing
Authors: Taehyung Kim, Joon Ho Moon, Jae-Sook Ahn, Marc S. Tyndel, Yeo-Kyeoung Kim, Seung-Shin Lee, Seo-Yeon Ahn, Sung-Hoon Jung, Deok-Hwan Yang, Je-Jung Lee, Seunghyun Choi, Yoojin Lee, Sang Kyun Sohn, Yoo Hong Min, June-Won Cheong, Hyeoung-Joon Kim, Zhaolei Zhang, Dennis Kim
Journal: Blood (2017)
Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: a multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial
Authors: Yu-Pei Chen, Xu Liu, Qin Zhou, Kun-Yu Yang, Feng Jin, Xiao-Dong Zhu, Mei Shi, Guo-Qing Hu, Wei-Han Hu, Yan Sun, Hong-Fen Wu, Hui Wu, Qin Lin, Hui Wang, Ye Tian, Ning Zhang, Xi-Cheng Wang, Liang-Fang Shen, Zheng-Zheng Liu, Jing Huang, Xiu-Ling Luo, Ling Li, Jian Zang, Qi Mei, Bao-Min Zheng, Dan Yue, Jing Xu, San-Gang Wu, Yan-Xia Shi, Yan-Ping Mao, Lei Chen, Wen-Fei Li, Guan-Qun Zhou, Rui Sun, Rui Guo, Yuan Zhang, Cheng Xu, Jia-Wei Lv, Ying Guo, Hui-Xia Feng, Ling-Long Tang, Fang-Yun Xie, Ying Sun, Jun Ma
Journal: The Lancet (2021)
Molecular characteristics of patients with resectable hepatocellular carcinoma.
Authors: Daobing Zeng, Menglong Wang, Jushan Wu, Dongdong Lin, Qingliang Guo, Chuanyun Li, Haitao Zhang, Liang Di, Xiaofei Zhao, Chao Ma, Daming Gao, Zhaobo Liu, Zhi Fu, Libo Sun, Qikun Zhang, Guangming Li, Rongyun Guo, Huina Wang, Yanrui Zhang
Journal: Journal of Clinical Oncology (2021)

e16140 Background: Hepatocellular carcinoma (HCC) is one of the most common malignancies and leading cause of cancer deaths worldwide. Biomarkers contribute to predict the response of targeted treatments and immunotherapy. Therapy directed toward homologous recombination deficiency (HRD) is now approved in ovarian and breast cancer, but the pattern of HRD is not clear in HCC. The HRD phenotype has been defined as the presence of a non-silent somatic mutation in homologous recombination-related (HRR) genes. Thus, we aimed to analyze the molecular characteristics of resectable HCC, including HRR genes. Methods: Matched tumor/normal DNA from resectable HCC patients (N = 53) were analyzed by whole exome sequencing (WES) or Acornmed panel with 808 cancer-related genes. Results: Overall, 94.3% (50/53) patients exhibited genetic alterations. TP53, ARID1A, PTEN and NBPF1 were the most commonly mutated genes in resectable HCC. In addtion, 35.9% patinets harbored at least one HRR genes mutation. The frequently mutated genes were BRCA2 (4.4%), BRCA1(4.0%), ATM (3.9 %), and RAD50 (3.8%). Interesting, frequency of HRR genes mutation in the Chinese cohort was higher than that in TCGA (35.9 % vs 20.9%). Analysis of carcinogenic pathways shown that ERBB and PI3K-AKT signaling pathway were the common signaling pathway. In resectable HCC, 32.08% (17/53) patients disclosed high TMB (highest 25%). Further analysis found that PTEN mutations were remarkably associated with low TMB (p &lt; 0.05). Conclusions: This study contributes to understand the molecular characteristics of patients with resectable HCC, which will be useful to guide personalized therapy and promote the clinical management in this population. Furthermore, the study suggested that it is feasibility for resectable HCC patients received PARP inhibitors, DNA-damaging chemotherapies, and immune checkpoint blockade therapy.
The association of HER2 low expression with the efficacy of CDK4/6 inhibitor in hormone receptor positive HER2 negative metastatic breast cancer.
Authors: Kelvin K H Bao, Leone Sutanto, Shirley S W Tse, Ka Man Cheung, Jeffrey C H Chan
Journal: Journal of Clinical Oncology (2021)

1052 Background: Markers for the efficacy of CDK4/6 inhibitor in estrogen receptor (ER) positive, HER2 negative advanced breast cancer are limited. The bidirectional crosstalks that exist between ER and HER2 pathways contribute to endocrine resistance. We investigated the association between low levels of HER2 expression and the clinical outcome of patients with ER+ HER2- metastatic breast cancer (MBC) treated with CDK4/6 inhibitors. Methods: We identified consecutive patients with ER+ HER2- MBC who received CDK4/6 inhibitor plus either letrozole or fulvestrant between Mar 2017 - Jun 2020 from an institutional cancer registry. HER2-low expression was defined as IHC score 1+, or 2+ with a negative ISH. Progression-free survival (PFS) was defined as the time from the initiation of CDK4/6 inhibitor to the date of radiological or clinical progression, or death. The relationship between HER2 expression levels and PFS was evaluated using log-rank test and multivariable Cox regression modelling. Results: 106 women with MBC were eligible for analysis. Median age at treatment was 58 (23.0-91.4). The majority received palbociclib (84%) while the rest received ribociclib. CDK4/6 inhibitor was used as first-line treatment in 50.9% of cases. Most tumors were of ductal histology (83%) and progesterone receptor (PgR) positive (84.9%), and 22.6% of the patients had bone-only disease. 77.3% of cases were considered HER2-low expressing. HER2-low expression was associated with a significantly shorter PFS compared with HER2 IHC 0 counterpart (median, 8.9 vs 18.8 months, p= 0.014). In multivariate analysis, HER-2 low expression remained significantly associated with an inferior PFS (HR 1.96, 95%CI 1.03-3.75, p= 0.041) after adjusting for the line of treatment, PgR status and disease extent (bone only vs extra-osseous disease). Conclusions: In patients with ER+ HER2- MBC treated with CDK4/6 inhibitors, HER2-low expression was associated with an inferior PFS, and may serve as a potential marker candidate for CDK4/6 inhibitor efficacy. As novel anti-HER2 antibody-drug conjugates demonstrated efficacy in HER2-low expressing MBC, coupled with the emerging evidence for the combination of CDK4/6 inhibitors with anti-HER2 agents, this HER2-low expression subgroup warrants prospective evaluations in future trials.
Oncology patient and provider preferences regarding rapid radiology result release to online portals.
Authors: Jonathan Bleeker, Jan Wernisch, Shawn Tronier, Shelby A. Terstriep
Journal: Journal of Clinical Oncology (2021)

1544 Background: Spurred by changes in legislation and technology, rapid patient access to medical results has never been higher. Many health systems now release results of radiology tests within 24 hours of completion, meaning patients may see results before being able to discuss them with the ordering provider. Generally, surveys have demonstrated that patients are in favor of rapid result availability, but research on rapid result release to oncology patients with distinct concerns is scant. Methods: Starting in February 2020, oncology providers throughout Sanford Health, a multi-site primarily rural integrated practice in the upper Midwest were invited to complete an online survey regarding their opinions on rapid result release. Starting in February 2020, oncology patients were invited to complete a similar survey. This survey was open until August 2020, when 100 patients had completed the survey; both surveys contained both categorical and narrative results. Results: Oncology providers had a generally more negative opinion of rapid radiology result release to online portals compared to patients. 65% of patients believed radiology results should be released within 24 hours of resulting; only 12% of providers shared this view. 66% of providers shared that they did not feel comfortable with patients’ ability to interpret radiology results and only 13% felt that “normal” results should be released immediately to an online portal; this number decreased to 3% when results were “abnormal”. Patient opinions on appropriate result release were impacted by test results as well. For “normal” radiology results, 50% of patients favored initial communication be via online portal without discussion with a provider; for “abnormal” results, this number decreased to 28%. 43% of patients had learned of an “abnormal” result via online portal before discussion with a provider; 66% of these patients felt that this was a positive which allowed them to process information prior to the visit; 33% felt that it created undue anxiety. 94% of providers reported having a patient contact them regarding a test result prior to a planned visit, with 60% providers sharing this happens at least once weekly. When asked what improvements could be made to the system currently in place at Sanford, 80% of providers suggested holding radiology results until direct communication with the provider can occur; only 8% of patients suggested the same intervention. Conclusions: Rapid result release is generally a patient satisfier, although oncology patients do distinguish abnormal from normal results in terms of rapid release. It is a dissatisfier for providers both due to concerns regarding patients’ ability to interpret results and due to excess work created by rapid release. Ongoing work should focus on ways to allow patients to access resources to make medical results more interpretable if reviewed prior to provider visits.
Optimizing chair time in infusion centers using intravenous cetirizine premedication for the prevention of hypersensitivity infusion reactions.
Authors: Julio Antonio Peguero, Ahmed Ayad, Stacia Young-Wesenberg, Teresa Yang, Janine North, Nancy Joseph-Ridge
Journal: Journal of Clinical Oncology (2021)

e13508 Background: Oncology infusion centers are increasingly focused on improving operational efficiencies and patient satisfaction, while maintaining quality care. One key component is optimizing chair time, which has been especially important for patient safety during the COVID-19 pandemic to reduce risk of transmission. Many infusions require antihistamine premedication to reduce the risk of hypersensitivity infusion reactions (IRs). The two IV options are IV diphenhydramine and IV cetirizine, which have a quicker onset than oral options and can be administered IV push. In treating acute urticaria, IV cetirizine was shown to be comparable to IV diphenhydramine, with fewer side effects, and it may be effective for preventing IRs with improved chair time. Methods: A randomized, double-blind phase 2 study evaluating premedication with single dose IV cetirizine 10 mg versus IV diphenhydramine 50 mg was conducted in 34 patients receiving paclitaxel, rituximab, its biosimilar or obinutuzumab (first cycle, retreatment after 6 months or with persistent IRs). The primary objective was the incidence of IRs after premedication. Secondary endpoints included sedation due to antihistamines and time to readiness for discharge. Sedation was reported by patients on a scale of 0-4 (0 = none to 4 = extremely severe). No formal statistical analyses were planned given the exploratory nature of the study. Results: Adults primarily with cancer (n = 31 [91%]) were enrolled during the COVID-19 pandemic, from March 25 to November 23, 2020. The median age was 65 and 67 years in the IV cetirizine and diphenhydramine groups, respectively. The number of patients with IRs was 2/17 (11.8%) with IV cetirizine versus 3/17 (17.6%) with IV diphenhydramine. The mean sedation score in the IV cetirizine group compared to the IV diphenhydramine group was lower at all time points, including at discharge (0.1 vs 0.4, respectively). Mean time to discharge was 24 minutes less with IV cetirizine (4.3 hours [1.5]) versus IV diphenhydramine (4.7 hours [1.2]). This difference was greater (30 minutes less) in those ≥65 years of age (4.4 [1.3] vs 4.9 [1.0] hours). Regardless of whether patients received paclitaxel (n = 9) or an anti-CD20 (n = 25), patients had less chair time when premedicated with IV cetirizine. There were fewer treatment-related adverse events (AEs) with IV cetirizine (2 events) than with IV diphenhydramine (4 events). Conclusions: This was the first randomized, controlled trial evaluating IV antihistamine premedication for IRs and chair time. It was shown that IV cetirizine can prevent IRs, with less sedation, fewer related AEs and reduced chair time compared to IV diphenhydramine. This improves infusion center operations and patient experience. Clinical trial information: NCT04189588.
A Treatise on Diseases of the Skin. For the Use of Advanced Students and Practitioners.
Journal: JAMA (1902)

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