tbuckley/cabot-search huggingface dataset:
CME curriculum improves clinician knowledge, competence, and confidence in managing patients with NF1-related tumors.
Authors: Michelle Arielle Worst, Rich Caracio, Katie Lucero, Jacob Cohen
Journal: Journal of Clinical Oncology (2021)

e23009 Background: Neurofibromatosis type 1 (NF1) is an uncommon complex autosomal dominant disorder caused by germline mutations in the NF1 tumor suppressor gene. Therapeutic options have historically been limited with surgical debulking being the preferred treatment modality. However, recent clinical data have shown improved outcomes with the use of MEK inhibitors. The objective of this study was to assess the educational impact of a series of continuing medical education (CME) activities on the knowledge, competence, and confidence of physician learners with respect to the treatment of NF1-related tumors. Methods: The educational series consisted of four online, CME-certified activities. For each activity, educational effect was assessed with a repeated pairs pre-/post-assessment study including a 3-item, multiple choice, knowledge/competence questionnaire and one confidence assessment question, with each participant serving as his/her own control. To assess changes in knowledge, competence, and confidence data from all clinicians who completed both pre- and post-questions were aggregated across activities, stratified by learning theme, and evaluated by target specialty. A repeated pairs pre-/post-assessment study design was used and McNemar’s test or paired samples t-test (P &lt; .05) assessed educational effect. The first activity in the series launched Dec. 2019 and the last launched June 2020; data were collected until Dec. 2020. Results: Overall significant improvements were seen after education for oncologists (N = 258, P &lt; .001), neurologists (N = 474, P &lt; .001), surgeons (N = 427, P &lt; .001), neurosurgeons (N = 93, P &lt; .05), and pediatricians (N = 56, P &lt; .001), regardless of practice setting. A sub-analysis of community specialists also showed significant improvements after education: oncologists (N = 117, P &lt; .01), neurologists (N = 188, P &lt; .001), and surgeons (N = 206, P &lt; .001). Outcomes assessed by learning themes and specialty showed relative percent increases, with the majority being statistically significant. Conclusions: This analysis demonstrates that oncologists’ and other specialists’ knowledge, competence, and confidence regarding the treatment of NF1-related tumors improved after education, as measured through a comprehensive analysis of CME outcomes data from a variety of activities designed to achieve these ends. These results have the ability to translate to improvements in clinical care. Despite the improvements, additional educational activities are needed to address residual gaps and further increase clinicians’ ability in this clinical setting.
HGG-34. A DNA DAMAGE REPAIR SIGNATURE IN PRIMARY AND RECURRENT PEDIATRIC HIGH-GRADE GLIOMAS: PROGNOSTIC AND THERAPEUTIC VALUE
Authors: Natacha Entz-Werle, Laetitia Poidevin, Petr Nazarov, Benoit Lhermitte, Marie Pierre Chenard, Olivier Poch, Monique Dontenwill, Eric Van Dyck
Journal: Neuro-Oncology (2021)

Abstract Pediatric high-grade gliomas (pHGGs), including diffuse intrinsic pontine gliomas (DIPGs), despite their low incidence, are the leading cause of mortality in pediatric neuro-oncology. Frequently, pHGGs, harboring mainly histone mutations, are or become resistant to standard therapies like irradiation or chemotherapies. Recent insights showed in adult HGG the predominant role of DNA damage repair (DDR) as a way of prognostic classification. Given the recent evidence that transcription conflicts like in histone-mutated gliomas can induce replication stress and be linked to DDR abnormalities, this study is aiming to establish a DDR signature able to classify specifically pHGGs and to cluster among them poor responders to radiation. Transcriptomic analyses were performed to discriminate seven pHGGs comparatively to a cohort of 10 pilocytic astrocytomas with specific DDR deregulations. The specific transcriptomic signature obtained from this differential gene expression analysis was compared to the aHGG signature already established. To strengthen, refine and finalize the DDR signature able to classify and cluster the pHGGs, we explored both signatures and their common genes in already published transcriptomic analyses of DIPGs and sus-tentorial pHGGs. To check DDR protein expressions correlated to loss of trimethylation as well as histone and TP53 mutations, an immunohistochemical assessment of several DDR markers was performed on a collection of 21 pHGG diagnostic samples and 9 paired relapses. To validate the DDR functional inhibition, we used 3 patient-derived cell lines bearing H3.3K27M mutations. A finalized signature of 28 genes involved in DNA repair and cell cycle machineries was used to cluster in two groups the pHGG cohorts. The differential protein expression of PARP1, XRCC1, p53 and stem cell markers was linked significantly to the more resistant pHGGs and the rapid progressions after radiotherapy. Those DDR makers might be used as theranostic and therapeutic targets, which were screened in PDCLs with promising results.
Automated immunostaining-free prediction of breast carcinoma ER and PR status, Ki67 count, patient therapy stratification index and quantification of prognostic quiescence burden in TNBC from pretreatment H&amp;E stained histopathology images in breast cancer.
Authors: Tathagata Dasgupta, Satabhisa Mukhopadhyay, Nicolas M Orsi, Michele Cummings, Angelene Berwick
Journal: Journal of Clinical Oncology (2021)

e12535 Background: Categorical combinations of ER, PR, HER2, and Ki67 levels are traditionally used to classify patients into luminal A and B-like subtypes in order to inform treatment choice. Accounting for nearly 70% of all breast malignancies, luminal cancer is heterogeneous, harboring subtypes with distinct molecular profiles and clinical outcomes. Although most patients with luminal-type disease respond well to endocrine therapy alone, some develop recurrences benefiting from additional cytotoxic therapy. Identifying such cases a priori remains a challenge but would enable patients to be spared the debilitating side-effects of ineffective chemotherapy. In this regard, the efficacy of chemotherapy and disease recurrence relate to (i) ER driven G1/S perturbations and/or (ii) quiescent cell populations arrested in the G0/G1 phase of cell cycle. This study aimed to develop a histopathology whole slide image (WSI)-based, low cost, rapid and automated approach to: (i) predict ER/PR/Ki67 status, (ii) quantify quiescence burden, (iii) develop a G1/S-based patient stratification system for luminal A/B patients, and (iv) achieve a quiescence burden-based stratification of TNBC patients. Methods: This investigation centered on the initial clinical validation of a novel, immunostaining-free technology which uses information extracted from pre-treatment hematoxylin and eosin (H&amp;E) stained slide WSIs alone to achieve these aims. Unlike conventional artificial intelligence-based approaches, the underlying proprietary algorithm and its prediction criteria are based on deterministic, hard-coded observational relationships of continuous scales drawn from WSI morphological features. In this instance, these represent tumor-related biological pathway disruptions and mitotic checkpoint perturbations, where G1/S perturbations enable luminal subtype stratification, and G0/G1 perturbations reflect quiescence burden. Back projecting the algorithm’s quiescence burden output on to the original WSIs enables morphological patterns to be mapped to quiescence burden.
Assessment of the treatment results in patients with breast cancer coexisting with pregnancy: A single-center observational study.
Authors: Anna Skrzypczyk-Ostaszewicz, Agnieszka I. Jagiello-Gruszfeld, Jerzy Giermek, Zbigniew Nowecki
Journal: Journal of Clinical Oncology (2021)

e12566 Background: This study discusses the analysis of the prospectively collected material on pregnant patients treated for breast cancer at the Department of Breast Cancer and Reconstructive Surgery of the Maria Skłodowska-Curie National Oncology Institute - National Research Institute (until 2020: Oncology Center - Institute) in Warsaw, in the years 1995 - 2020. 84 patients were included into the final analysis and 72 children were assessed simultaneously. Methods: The paper summarizes information on the diagnosis and treatment of breast cancer during pregnancy, the course of pregnancy and childbirth and the birth parameters of children i.e. weight, length and Apgar score, as well as the dependencies between them, mainly the impact of some breast cancer, diagnosis and treatment process features on the newborns. The patietnt’s survavial - DFS ( disease free survival) and OS ( overall survival) - was also analyzed. The course of breast cancer diagnosis and treatment data were obtained from the patients’ medical documentation (medical records) and from information provided by the mothers during follow-up visits and read in the children's health books. In order to answer the research questions, statistical analyzes were conducted using the IBM SPSS Statistics 26 package. Results: In the analyzed period, the disease recurrence was recognized in 34 (40.5%) patients, and 24 (28.6%) patients died. The median disease-free survival (DFS) was 12.3 years (147.5 months), and the median overall survival (OS) was not reached during the follow-up period. The estimated 5-year survival rates for DFS and OS were 57.9% and 74.5% respectively, and for 10-year survival - 51.4% and 64.5%. The study showed a statistically significant relationship between the baseline clinical advancement and DFS. It has been also analyzed how the diagnosis, treatment and method of pregnancy termination changed in two time periods (1995-2012 and 2013-2020). There were no statistically significant differences in survival - both DFS and OS - between the group of patients treated before and after 2012. In the assessment of the impact of some factors on the birth children parameters (weight and length), statistically significant results were obtained for: pregnancy advancement at diagnosis, breast cancer stage at diagnosis, pregnancy advancement at the start of chemotherapy, the chemotherapy regimen (classic or dose-dense), the number of cycles of chemotherapy given during pregnancy, and the number of drugs used in supportive treatment. Conclusions: The entire analysis has become not only an insightful characteristic of the studied group, but also these results may be important in everyday clinical practice and may help to optimize the management of an extremely complex and difficult situation, which is the coexistence of pregnancy with a malignant disease that threatens the mother’s life.
ST2 As a Biomarker of Non-Relapse Mortality after HLA-Haploidentical SCT with High-Dose Post-Transplantation Cyclophosphamide
Authors: Laura Solán, Carolina Martínez-Laperche, Mi Kwon, Diego Carbonell, Pascual Balsalobre, David Serrano, María Chicano, Julia Suárez-González, Javier Anguita, Jorge Gayoso, Ismael Buño, Jose L. Diez-Martin
Journal: Blood (2017)
Access to radiation oncology centers with brain tumor treatment expertise for patients with resectable brain tumors.
Authors: Mehee Choi, Brian P. Martin, Lisa Misell, Joseph M. Zabramski, David G. Brachman
Journal: Journal of Clinical Oncology (2021)

e18509 Background: Many patients with brain tumors face challenges with access to care. For rural patients, prolonged travel times may limit access to appropriate radiotherapy. Radiation centers (RCs) offering specialized brain radiotherapy, e.g., stereotactic radiosurgery (SRS), are geographically limited. Utilization of brain brachytherapy at the time of resection offers an option for such patients, but technical challenges have limited the adoption. To address the limitations of traditional brachytherapy, a device with Cs-131 seeds embedded in a bioresorbable collagen tile (GammaTile, GT Medical Technologies, Tempe, AZ USA) was developed. GammaTile (GT) is FDA-cleared for permanent implantation at the time of resection for all recurrent intracranial tumors and for newly diagnosed malignant intracranial neoplasms. To investigate if wider availability of this treatment could possibly lower the geographic barrier to access to care, we mapped the US population against existing RCs with brain tumor expertise and neurosurgery centers (NSCs) performing craniotomies. Methods: We analyzed 2018 CMS claims data using CPT codes for single- and multi-fraction SRS to identify RCs with brain tumor treatment expertise and mapped these against the population. Using similar methodology, using CPT codes for craniotomies, we identified NSCs, as any facility performing craniotomies is potentially eligible to implant GT. Results: 135 RCs used CPT codes for SRS. 193-, 119-, 82-, and 52-million Americans lived &gt;30-, &gt;60-, &gt;90-, and &gt;120-minutes from one of these centers, respectively. 530 NSCs preform craniotomies, including ≥1 in every state, a 4-fold increase over the number of RCs offering SRS. Conclusions: For many patients, substantial travel distances limit their access to RCs with brain tumor treatment expertise. In contrast, the 530 craniotomy-performing NSCs have far greater geographic dispersion. The option of undergoing brain radiation with GT implantation at the time of brain tumor craniotomy brings treatment closer to millions, ensures compliance, and reduces additional travel for follow-up radiation treatment.[Table: see text]
Phase II trial of combined durvalumab plus tremelimumab with proton therapy to boost the abscopal effect for recurrent or metastatic head and neck squamous cell carcinoma.
Authors: Hana Kim, Myung-Ju Ahn, Dongryul Oh, Sehhoon Park, Hyun Ae Jung, Se-Hoon Lee, Keunchil Park, Yong Chan Ahn
Journal: Journal of Clinical Oncology (2021)

6034 Background: This phase 2 study investigated whether durvalumab plus tremelimumab with proton therapy improves objective response rate (ORR), overall survival (OS), and progression-free survival (PFS) in heavily treated recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) via boosting abscopal effect. Methods: Thirty-one patients who have previously received more than one chemotherapy regimen, including at least one platinum-based regimen and have at least two measurable lesions enrolled at Samsung medical center. Patients received durvalumab 1500mg intravenously (IV) in combined with tremelimumab 75 mg IV every four weeks for four cycles followed by durvalumab 1500mg every four weeks. After one cycle of durvalumab and tremelimumab combination, proton therapy was performed with a total dose of 25 Gy in 5-Gy daily fractions to one of the measurable lesions. We assessed the target lesion response outside the radiation field by RECIST criteria 1.1 to evaluate the abscopal effect. Results: Between March 2018 and July 2020, 31 patients were enrolled. The median age was 59 years, and median two prior chemotherapy regimens were administered. With 24.8 months of follow-up, the median number of cycles of immunotherapy was three. The ORR was 27.3%, including one complete response and five partial responses. Median OS was 6.4 months (95% CI, 1.0 to 11.8), and median PFS was 2.4 months (95% CI, 0.6 to 4.2). Median duration of response was 15.9 months (range 3.7 – 21.2). Grade 3 or higher adverse events were observed in 6 (27.3%) patients; anemia (n = 1), constipation (n = 1), electrolyte imbalance (n = 2), hyperglycemia (n = 1), pneumonia (n = 1). Conclusions: Combination of durvalumab/tremelimuab with proton therapy is well tolerable and shows encouraging anti-tumor efficacy in non-irradiated tumor lesions of heavily treated HNSCC patients. These results suggest that the combination of immunotherapy with proton therapy might enhance the abscopal effect. Clinical trial information: NCT03450967.
Attributes and disease characteristics of patients seeking online second opinion for cancer.
Authors: Rakesh Shankar Goud, Amit Kumar Jotwani, Thirtha Poovaiah, Rejil Rajan, Rama Waghmare, Shashidhar Gururao
Journal: Journal of Clinical Oncology (2021)

e13620 Background: As we see rising cancer incidence in India, there is a parallelly increasing trend in patient-driven second medical opinions (SMO) in oncology. We analysed different attributes of patients seeking online second opinions through onco.com to help us understand the driving factors for patients. Here we present the patient and disease attributes to understand the reasons and perceived value of SMOs in oncology through an online platform. Methods: We did a retrospective analysis of 1,142 patients who availed online tumor board opinion through Onco.com between August 2018 &amp; December 2020. Patient characteristics like age, gender, city of residence (metro or non-metro) &amp; disease characteristics like cancer type and stage were recorded. Tumors included both solid and hematological malignancies. Results: Of the 1,142 patients, 87% (991) cases were solid tumors and the rest 13% (151) were hematological malignancies. Top 6 cancer types for which patients sought SMOs- Breast- 13%, Head &amp; neck- 8.7%, Lung- 7.5%, Leukaemia- 5.8%, Lymphoma- 5.4%, &amp; Ovarian- 5% cancers. Of the 991 solid tumour cases, 13% had early (stage I &amp; II) disease, 24% had locally advanced (stage III) disease, 52% had metastatic disease &amp; and 11% had recurrent disease. The mean age of patients was 50 years with equivalent gender distribution. 23% of patients seeking SMOs were young adults (17-44 years), 59% were older adults (45-70 years), and 9% patients were from elderly (&gt;70 years) age group. City of residence- 39% patients were residents of metro (tier 1) cities and 61% were residents of non-metro (tier 2/3) cities. Conclusions: Advanced stage of disease (metastatic + recurrent) and non-metro city of residence were found to be the commonest attributes for majority of patients. Desperate nature of the situation in advanced stage of disease and lack of access to specialised oncology care in non-metro cities respectively appear to be the reasons for higher SMOs in these groups. Higher number of SMOs for younger age patients was disproportionate to the incidence of cancer in this age-group. A larger analysis of the contrarian opinions, compliance and clinical impact of second opinions in terms of better survival outcomes is warranted to see if patients get true value out of this exercise.
Epigenomic analysis of biliary tract cancer identifies subtypes with different immune characteristics and clinical outcomes.
Authors: Zhiquan Qiu, Jun Ji, Yu Xu, Yan Zhu, Chun-Fang Gao, Guoqiang Wang, Chengcheng Li, Yuzi Zhang, Jing Zhao, Chenyang Wang, Xiaofang Wen, Zhou Zhang, Bingsi Li, Han Han-Zhang, Hao Liu, Shangli Cai, Zhihong Zhang, Bin Li, Xiaoqing Jiang
Journal: Journal of Clinical Oncology (2021)

e16153 Background: Biliary tract cancer (BTC) is an aggressive malignancy with poor prognosis and limited treatment options. The epigenome-associated multi-dimensional studies for BTC are limited. Here, we proposed a DNA methylation-based classification scheme and investigated the associations between methylation and multi-dimensional data including clinicopathological features, genetic aberrations, and prognosis. Methods: Multi-dimensional data concerning mutation, DNA methylation, and clinical data from 105 BTC patients who received surgical resection (gallbladder cancer [GBC], n=48, cholangiocarcinoma [CCA], n=57) were analyzed. Differentially methylated blocks (DMBs) in GBCs and CCAs were identified by comparing tumors and adjacent tissues. Methylation-based subtyping was performed via non-supervised consensus clustering. Results: The differentially methylated blocks (DMBs) in GBCs and CCAs are highly overlapping. Based on the common DMBs of GBCs and CCAs, the classifier yielded high sensitivity of 95.2% and specificity of 96.0%. Hypomethylated genes were enriched in pathways of transmemberane receptor and ion binding, while hypermethylation occurred in genes concerning DNA binding transcription activity. By non-supervised clustering of common DMBs, 6 clusters with different degrees of methylation change were identified. Higher methylation alteration (cluster risk-high) was associated with more copy number variation and shorter OS. By LASSO regression, a 12-gene prognostic model was trained and validated (Table). As for immune characteristics, the methylation of CD8A gene was lower in the cluster risk-high group, and this association was validated in the TCGA-cholangiocarcinoma cohort. In addition, lower methylation change was associated with higher BCR/TCR diversity, immune cell infiltration, and PD-L1 and CTLA4 mRNA expression. Conclusions: In BTC, methylation patterns may serve as a robust indicator of immune-related features and prognosis. Our integrative analysis highlights the association between genomic and epigenomic features, and provides insights into the molecular heterogeneity, and the potential therapeutic significance in biliary tract malignancies. Included methylation sites in the LASSO model.[Table: see text]
Abstract 16925: In Vivo Crosstalk Between Transplanted Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Host Myocardial Cells
Authors: Sang-Ging Ong, Bruno C Huber, Antje Ebert, Kazuki Kodo, Joseph D Gold, Robert C Robbins, Joseph C Wu
Journal: Circulation (2013)

Objectives: Induced pluripotent stem cell (iPSC) and their derivatives are attractive candidates for therapeutic use, with the potential to replace deficient cells and to improve functional recover...