tbuckley/cabot-search huggingface dataset:
Efficacy of platinum-based regimens as the first-line therapy in Chinese patients with advanced TNBC and deleterious BRCA1/2 mutations.
Authors: Nan Wang, Kun Li, Wei-Yao Kong, Xiao-Ran Liu, Meng-Yao Tan, Han-Fang Jiang, Guo-Hong Song, Lijun Di, Quanren Wang, Amy Wang, Jianjun Yu, Shidong Jia, Huiping Li
Journal: Journal of Clinical Oncology (2019)

e12565 Background: Platinum-based therapy remains an effective treatment for triple-negative breast cancer (TNBC), however, the usage is largely limited due to its side effect and rapidly developed drug resistance. High prevalence of BRCA1/2 mutations are reported in TNBC. Here we explored efficacy of platinum-based regimens as the first-line treatment for Chinese patients (pts) with advanced TNBC, and analyzed its association with mutations of germline BRCA1/2 (gBRCA). Methods: We retrospectively analyze 220 patients diagnosed as advanced TNBC who were treated at the Dept. of Breast Oncology, Peking University Cancer Hospital in 2013-2018, and routinely evaluated by RECIST 1.1. Statistical analysis is performed in R 3.5.1. Cox proportional-hazard models are used for survival analysis. Results: 129 pts received non-platinum chemotherapy (NPCT) as the first-line therapy, and 91 pts received platinum-based chemotherapy (PBCT). The clinical benefit rate (CBR) and median PFS were not statistically different between NPCT and PBCT groups The median OS was 30.0 and 22.5 months for PBCT and NPCT group respectively (P = 0.09, HR = 0.70). Among them, 114 pts had BRCA gene tested, of which 14 had deleterious gBRCA mutations, 7 in each group. In PBCT group, the CBR was 85.7% and 35.1% for pts with and without deleterious gBRCA mutations respectively (P = 0.04). The median PFS, OS were 14.9 months and 5.3months (P = 0.001), 26.5 and 15.5 months (P = 0.16) for pts with and without the gBRCA mutations. No significant difference was observed between NPCT pts with and without gBRCA mutations as regards the CBR, PFS and OS. PBCT Pts had significantly more grade 3-4 anaemia (5.5% vs 0%) and thrombocytopenia (8.8% vs 0%) while higher percentage of palmar-plantar erythrodysesthesia (PPE) (12.4% vs 0%) and peripheral neuropathy (8.6% vs 1.1%) were observed in NPCT pts. Conclusions: The efficacy of platinum-based regimens as the first-line treatment of advanced TNBC insignificantly differs from that of non-platinum therapy. However, they are more effective for patients with deleterious gBRCA mutations, suggesting a BRCA1/2 genetic testing may be warranted for such patients.
AB0950 CORRELATION OF QUANTITATIVE MAGNETIC RESONANCE IMAGING BIOMARKERS AND AXIAL PAIN IN ENTHESITIS-RELATED ARTHRITIS PATIENTS
Authors: Varvara Choida, Tim Bray, Anna Radziszewska, Corinne Fisher, Coziana Ciurtin, Debajit Sen, Margaret Hall-Craggs
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Magnetic resonance imaging is increasingly used to diagnose, stratify and monitor inflammation in patients with spondyloarthritis, including young patients with enthesitis-related arthritis (ERA). Recently, there has been interest in the use of quantitative magnetic resonance imaging (qMRI) as an objective method of assessing disease. For example, diffusion-weighted imaging (DWI) and fat fraction (FF) mapping have emerged as biomarkers of oedema and structural damage, respectively, in inflamed bone<sup>1</sup>. However, as yet there are limited data to tie these biomarkers to underlying immunopathology. <h3>Objectives</h3> To analyse the relationships between quantitative imaging biomarkers (QIBs), axial pain and serum biomarkers – including 'inflammatory' biomarkers and those reflecting bone turnover - in a cohort of ERA patients. <h3>Methods</h3> 28 patients with ERA were prospectively recruited. The hips, sacroiliac joints and lumbar spine were assessed with chemical shift-encoded MRI and diffusion weighted imaging. Quantitative MRI parameters, such as the apparent diffusion coefficient (ADC) and fat fraction (FF) were measured in the sacroiliac joints. Visual scores for inflammation and fat metaplasia were also reported. BASDAI questionnaires were completed. Serum cytokines and bone markers were measured via multiplex bead-based immunoassays (Luminex) and results were available for 14 patients with ERA. <h3>Results</h3> The mean visual analogue score for spinal and hip pain (BASDAI Q2) was 3.9 (Table 1). There was a correlation between ADCmean and spinal and hip pain (rs=0.393, P=0.043). There was also a negative correlation between FFmean and the above pain score (rs = -0.378, P=0.047). There was a positive correlation between matrix metalloproteinase-3 (MMP-3) levels and FFmean (n=14, rs=0.698, P=0.006). However, the correlation did not reach statistical significance when corrected for multiple testing. <h3>Conclusion</h3> The correlation of ADCmean, which increases with increased tissue water/inflammation, with spinal and hip pain suggests that BASDAI Q2 relates to pain of active inflammation. Similarly the inverse correlation of FFmean, which increases with bone healing and reduced inflammation, and BASDAI Q2, would also support this relationship. <h3>References</h3> [1] Bray TJP, Bainbridge A, Punwani S, Ioannou Y, Hall-Craggs MA. Simultaneous Quantification of Bone Edema/Adiposity and Structure in Inflamed Bone using Chemical-Shift Encoded MRI in Spondyloarthritis. Magnetic Resonance in Medicine2018Feb;79(2):1031-1042 <h3>Disclosure of Interests</h3> None declared
Recapitulation of inflammatory and immune-evasive subtypes of oral cancer cells in immunodeficient mice.
Authors: Su-Fang Lin, Ying-Chieh Ko, Fu-Hui Wang, Sheng-Yao Su, Yu-Lian Chen, Ting-Yu Lai, Yi-Hong Liu, Chung-Yen Lin, Shu-Ching Hsu
Journal: Journal of Clinical Oncology (2019)

e14199 Background: Prior study stratified Taiwanese oral cancer specimens (n = 40) and cell lines (n = 7) into three distinct molecular subtypes, namely classical (CL), mesenchymal (MS), and basal (BA). In a cell line derived xenograft (CDX) model, we observed MS grew at least 10-fold slower than CL did in immunodeficient mice. By using RNA-seq to portrait the transcriptomes of human tumor and mouse stroma simultaneously, contribution of mouse innate immunity in restricting the growth of human oral cancer cells was assessed. Methods: A half millions of mycoplasma-free OC3 (MS) or TW2.6 (CL) cells with matrigel were subcutaneously implanted into the flank of 10 to 16 weeks old NOG (NOD/SCID/Il2rgtm). RNAs of CDX tissues from OC3-NOG (n = 7) and TW2.6-NOG (n = 5) were extracted and subjected to stranded mRNA sequencing. Clean reads were aligned to GRCh38 (human) and GRCm38 (mouse), respectively, followed by identifying differentially expressed genes and gene set enrichment analysis. Results: Up-regulation of signature genes for dendritic cells and macrophages and enrichment of innate immunity, including Tnfa-Nfkb signaling, interferon alpha response, interferon gamma response and inflammation were detected in OC3- but not in TW2.6-CDXs. These results suggested that OC3 (MS) was more immunogenic than TW2.6 (CL), which is reminiscent of the inflammatory MS (IMS) subtype of head and neck cancer recently described by Keck et al (n = 938, Clin Cancer Res 2015, 21: p870. PMID: 25492084). Conclusions: By RNA-seq/xenome analysis of CDXs, we provide evidence that compared to CL, MS subtype of oral cancer cells elicited a stronger innate immunity in NOG mouse. Alternatively, CL subtype might have evolved as a prototype with superiority in immune escape.
Capmatinib (INC280) in <i>METΔex14</i>-mutated advanced non-small cell lung cancer (NSCLC): Efficacy data from the phase II GEOMETRY mono-1 study.
Authors: Juergen Wolf, Takashi Seto, Ji-Youn Han, Noemi Reguart, Edward B. Garon, Harry J.M. Groen, Daniel Shao-Weng Tan, Toyoaki Hida, Maja J. De Jonge, Sergey V. Orlov, Egbert F. Smit, Pierre Jean Souquet, Johan F. Vansteenkiste, Monica Giovannini, Sylvie Le Mouhaer, Anna Robeva, Maeve Waldron-Lynch, Rebecca Suk Heist
Journal: Journal of Clinical Oncology (2019)

9004 Background: Capmatinib is a highly potent and selective MET inhibitor. Previous data of GEOMETRY mono-1 study showed a clinically meaningful overall response rate (ORR) and manageable toxicity profile in patients (pts) with METΔex14–mutated NSCLC who received 1–2 prior lines of treatment (tx) (Cohort 4) and in particular a high ORR in tx-naïve pts (Cohort 5b). Here we report the results in METΔex14–mutated NSCLC for duration of response (DOR) and progression-free survival (PFS) as well as the updated results for ORR. Methods: GEOMETRY mono-1 is a phase 2, multi-cohort, multicenter study evaluating capmatinib in pts with METΔex14-mutated or MET-amplified advanced NSCLC across 6 cohorts. Pts (≥18 yrs) with ECOG PS 0–1, ALK and EGFR wt, and stage IIIB/IV NSCLC were eligible. Pts with METΔex14 mutation (centrally confirmed) were assigned (regardless of MET amplification status/gene copy number) to Cohorts 4 and 5b and received capmatinib tablets 400 mg BID. Primary endpoint was ORR by Blinded Independent Review Committee (BIRC) per RECIST v1.1. Key secondary endpoint was DOR by BIRC. Results: As of Nov 08, 2018, 97 pts with METΔex14-mutated NSCLC (Cohort 4: 69 pts; Cohort 5b: 28 pts) were evaluable for efficacy. ORR (95% CI) by BIRC was 39.1% (27.6-51.6) in Cohort 4 and 71.4% (51.3-86.8) in Cohort 5b. While still immature at the time of this analysis, data on durability are promising: median DOR (95% CI) by BIRC was 9.72 (4.27-11.14) and 8.41 (5.55-NE) mo for Cohorts 4 and 5b, respectively; median PFS (95% CI) by BIRC was 5.42 (4.17-6.97) and 9.13 (5.52-13.86) mo for Cohorts 4 and 5b, respectively. Safety profile remains favourable and unchanged. Most common AEs (≥25% all grades) across all cohorts (n = 315), were peripheral edema (49.2%), nausea (43.2%), and vomiting (28.3%); majority of the AEs were grade 1/2. Final efficacy analysis (12-mo f-u on DOR) including biomarker data will be presented during meeting. Conclusions: These data confirm capmatinib to be a promising new treatment option for pts with METΔex14-mutated advanced NSCLC regardless of the line of therapy with deep and durable responses and manageable toxicity profile. Clinical trial information: NCT02414139.
Survey of medical student knowledge in oncology and survivorship care in Nigeria: A pilot study.
Authors: Jim Leng, Abiola Falilat Ibraheem, Atara Isaiah Ntekim, Abiodun Popoola, Luther Agaga, Emmanuel Ukoh, Daniel William Golden, Olufunmilayo I. Olopade
Journal: Journal of Clinical Oncology (2019)

e18106 Background: In low middle-income countries (LMICs), cancer patients present in later stages of disease for many reasons, including missed diagnoses. Due to high patient: physician ratios, generalists are taught broadly and prepared to treat diseases outside the scope of their interest in training. The delivery of high-quality cancer care requires an interdisciplinary team of physicians with excellent medical school training in oncology. To date, there has been no formal assessment of medical education for oncology in Nigeria. This study aims to assess the ability of the curriculum in Nigeria to prepare future doctors tasked with treating a growing number of patients with cancer. Methods: An anonymous survey was administered to final year medical students at Lagos State University and University of Ibadan, Nigeria. The survey assessed demographics, reports of experience during medical school with oncology, comfort ratings with different aspects of oncologic care (Likert scale, 1 = not at all, 5 = extremely), and included five clinical vignettes. Results: 146 graduating students in two medical schools responded (response rate = 36.6%). Twelve percent of students indicated that they planned to pursue a career in oncology. The majority of students reported exposure through lectures to medical oncology (85%), radiation oncology (82%), and surgical oncology (85%), but fewer reported exposure to lectures in hospice care (75%) and cancer survivorship care (52%). Most students (87%) have not attended a tumor board during medical school. In clinical vignettes, students performed worst on long-term chemotherapy toxicities, and best on surgical oncology risk. Overall, students indicated being “moderately comfortable” with topics in medical, radiation, surgical, and palliative care on a Likert scale, and “somewhat comfortable” with survivorship care. Conclusions: Although students in Nigeria report learning about disciplines in oncology care, they report varying comfort levels with specific oncology topics by the end of medical school. The results of this pilot study support the need to develop an interdisciplinary oncology curriculum in Nigeria.
<i>Kras</i> and <i>Lkb1</i> mutations synergistically induce intraductal papillary mucinous neoplasm derived from pancreatic duct cells
Authors: Louis Collet, Elsa Ghurburrun, Nora Meyers, Mohamad Assi, Boris Pirlot, Isabelle A Leclercq, Anne Couvelard, Mina Komuta, Jérôme Cros, Pieter Demetter, Frédéric P Lemaigre, Ivan Borbath, Patrick Jacquemin
Journal: Gut (2019)

Pancreatic cancer can arise from precursor lesions called intraductal papillary mucinous neoplasms (IPMN), which are characterised by cysts containing papillae and mucus-producing cells. The high frequency of KRAS mutations in IPMN and histological analyses suggest that oncogenic KRAS drives IPMN development from pancreatic duct cells. However, induction of Kras mutation in ductal cells is not sufficient to generate IPMN, and formal proof of a ductal origin of IPMN is still missing. Here we explore whether combining oncogenic KrasG12D mutation with an additional gene mutation known to occur in human IPMN can induce IPMN from pancreatic duct cells.We created and phenotyped mouse models in which mutations in Kras and in the tumour suppressor gene liver kinase B1 (Lkb1/Stk11) are conditionally induced in pancreatic ducts using Cre-mediated gene recombination. We also tested the effect of β-catenin inhibition during formation of the lesions.Activating KrasG12D mutation and Lkb1 inactivation synergised to induce IPMN, mainly of gastric type and with malignant potential. The mouse lesions shared several features with human IPMN. Time course analysis suggested that IPMN developed from intraductal papillae and glandular neoplasms, which both derived from the epithelium lining large pancreatic ducts. β-catenin was required for the development of glandular neoplasms and subsequent development of the mucinous cells in IPMN. Instead, the lack of β-catenin did not impede formation of intraductal papillae and their progression to papillary lesions in IPMN.Our work demonstrates that IPMN can result from synergy between KrasG12D mutation and inactivation of a tumour suppressor gene. The ductal epithelium can give rise to glandular neoplasms and papillary lesions, which probably both contribute to IPMN formation.
SP0122 OPTIMIZING HOLLISTIC TREATMENTS: THE CHALLENGE OF IMPLEMENTATION
Authors: Krysia Dziedzic
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> International guidelines present recommendations for holistic care for RMDs, building upon best evidence. However, there is still a gap between what we know about best care and what we do to implement best care in our clinical services. Having EULAR guidelines alone (and multiple updates and revisions) is not enough to change complex systems. European funders are now investing in projects to accelerate the uptake of best care across multiple European partners. Using one example of a completed EIT-Health funded implementation project, JIGSAW-E (Joint Implementation of Guidelines for oSteoArthritis in Western Europe), this presentation will highlight some of the challenges of implementation such as: understanding the context; competing priorities; lack of time and funding; stability of the workforce; and differing health care systems. It will describe the use of Knowledge Mobilization and Communities of Practice as methods for overcoming these challenges and optimizing holistic treatments. The presentation will offer some of the key factors for implementation such as 'leading from the middle" and brokering across silos; working with patients and the public '<i>Patients are the most under-</i><i>used resource in any health care system";</i> using theories, models and frameworks to plan, understand and evaluate implementation; using pilot sites to build momentum with dedicated Communities of Practice; and agreeing what success should look like. <h3>Disclosure of Interests:</h3> None declared
Cost-effectiveness of CHOP in treating DLBCL in Malawi.
Authors: Matthew Painschab, Racquel Elizabeth Kohler, Stephanie B. Wheeler, Satish Gopal
Journal: Journal of Clinical Oncology (2019)

6644 Background: DLBCL is common in Africa, and often curable, but treatment costs and cost-effectiveness are key considerations. WHO defines extremely cost-effective interventions as having an incremental cost-effectiveness ratio (ICER) &lt; GDP per capita. Methods: We used a decision tree model to conduct a cost-effectiveness and budget impact analysis from a health systems perspective in Malawi (2017 GDP per capita $340). Comparisons were made between CHOP vs. palliative care with diagnosis (PC+D), and palliative care without diagnosis (PC-D). Microcosting and clinical outcomes were derived from published prospective data. Costs reflect treatment and 2 years of follow-up. Outcomes reflect a lifetime time horizon. Life expectancies were derived from UNdata, and disability-adjusted life year (DALY) weights from the Global Burden of Disease Study. Costs were analyzed in 2017 US $, and costs and outcomes were discounted at 3% annually. Annual estimates for new DLBCL cases (n=161) were used as input incidence. Probablistic sensitivity analysis was conducted using Crystal Ball software over 1000 simulations. Results: For the base case, the ICER of CHOP versus PC+D is $150/DALY averted, and versus PC-D is $200/DALY averted (Table). The ICER was stable across a wide range of sensitivity analyses. The ICER varied most across the range of progression-free survival estimates ($117-209), and range of costs for CHOP plus follow-up ($71-308). CHOP was extremely cost-effective by the WHO definition in 99% of simulations versus PC+D, and 94% of simulations versus PC-D. In the base case, total annual cost of DLBCL treatment with CHOP in Malawi was $306,221. Conclusions: This is one of the first rigorous cost-effectiveness and budget impact analyses for cancer treatment in a low-income country. CHOP is extremely cost-effective compared to palliative care, with ~$300,000 needed annually to treat all DLBCL cases in Malawi. These findings merit external validation, and support continued regional investments in cancer care. [Table: see text]
Dosimetric and radiobiological comparison of external beam radiotherapy using simultaneous integrated boost technique for esophageal cancer in different location.
Authors: Lu Wang, Jinming Yu
Journal: Journal of Clinical Oncology (2019)

e15505 Background: Based on dosimetry and radiobiology to compare treatment plans for esophageal cancer (EC) in different location using intensity modulated radiotherapy (IMRT), volumetric modulated arc radiotherapy (VMAT) and helical tomotherapy(HT) with simultaneous integrated boost (SIB) technique. Methods: A total of 20 patients including 5 cases respectively located in the cervix, upper, middle and lower thorax were generated for IMRT, VMAT and HT plans. The dose volume histogram statistics, conformity index (CI), homogeneity index (HI), tumor control probability (TCP) and normal tissues control probability (NTCP) were analyzed to evaluate treatment plans. Results: HT showed significantly improvement over IMRT and VMAT in terms of CI(0.93±0.03), HI(0.07±0.03) and TCP(88.08±0.82%) in cervical EC(p&lt;0.05). IMRT greatly developed TCP(88.29±1.79%;85.11±0.79%), and offered superior CIs (0.87±0.04;0.90±0.01) and HIs(0.10±0.01; 0.06±0.01) compared with VMAT and HT in upper and middle thoracic EC(p&lt;0.05). Meanwhile, the V30(33.30±6.49%), mean dose (2559.00±219.64cGy) and NTCP(0.50±0.61%) of heart for IMRT were significantly reduced than other two techniques in middle thoracic EC. Patients with lower thoracic EC yielded the similar CIs and HIs(all p&gt;0.05) for the 3 techniques, but VMAT showed the lowest NTCP of lungs (0.01±0.01%) with improved TCP (84.84±1.13%). Conclusions: HT was a good option with little lung and heart involvement as it achieved superior dose conformality and uniformity. IMRT was a perfect strategy with large thoracic involvement. It significantly improved tumor local control and reduced heart dose and complications with acceptable dose to lungs. VMAT was preferred with a smaller target volume but surrounded by more heart and less lungs. Individually choosing optimal technique for EC in different location will be warranted.
Role of radiomics to differentiate benign from malignant pheochromocytomas and paragangliomas on contrast enhanced CT scans.
Authors: Bahar Laderian, Firas Salem Ahmed, Binsheng Zhao, Julia Wilkerson, Laurent Dercle, Hao Yang, Xiaotao Guo, Karel Pacak, James A. Lee, Susan Elaine Bates, Jaydira Del Rivero, Lawrence Howard Schwartz, Antonio Tito Fojo
Journal: Journal of Clinical Oncology (2019)

e14596 Background: Radiomics features, which are quantitative features generated by computational analysis of routine clinical imaging like CT scans, have been shown to be associated with clinical outcomes and tumor’s behavior in some solid tumors. We compared the radiomic features of malignant and benign pheochromocytomas/paragangliomas (P/P). Methods: Through an IRB approved study at our institution, we identified 20 consecutive patients with P/P and with available contrast-enhanced abdominopelvic CT. A radiologist with experience in oncologic imaging identified and segmented tumors on every slice using a MatLab-based imaging platform. The entire tumor image then underwent computational analysis generating 1160 radiomics features reflecting tumor size, shape, density, textural heterogeneity, and margins. These radiomics features were compared between malignant and benign P/P using Wilcoxon-Rank sum test. Results: Of the twenty patients included in this analysis, there were 6 patients with malignant P/P and 14 patients with benign tumors. Patients had been followed for at least 5 and many for at least 10 years after resection of the tumor. At diagnosis, the mean age of patients with benign and malignant tumors were 51 and 45, respectively. A 60% majority of patients with benign tumors were females while a 77% majority of patients with malignant tumors were male. Benign P/P were significantly different from malignant ones in: tumor intensity textures (spatial correlation [p-value = 0.0010], Laws [p-value = 0.0064], LoG [p-value = 0.0087], and Gabor [p-value = 0.0325]), and tumor local surface shape (Shape Index SI7 [p-value = 0.0325]). Conclusions: This initial analysis sought to discern differences in these rare tumors that might be exploited clinically. The results show that compared to benign tumors, malignant P/P tend to have more heterogenous texture, irregular edges, and less rounded shape on contrast enhanced abdominal CT scan. However, because these radiomics phenotype properties are subtle, they cannot be made reliably in an objective fashion using human visual assessment and thus these radiomics features may have a role as a quantitative imaging biomarker in P/P to predict tumor behavior. The cohort is being expanded and data will be updated at the time of the presentation. With larger numbers, the contribution to the radiomics profile of a SDHx mutation will be explored in greater depth to understand the differential impact of SDHx loss and of evolution into a cancer to the radiomics profiles.