tbuckley/cabot-search huggingface dataset:
A phase II trial of cabozantinib (CABO) for the treatment of radioiodine (RAI)-refractory differentiated thyroid carcinoma (DTC) in the first-line setting.
Authors: Marcia S. Brose, Sangeeta Shenoy, Nikhil Bhat, Anne K Harlacker, Raven K. Yurtal, Zakkiyya A Posey, Dena M Torrente, Carolyn Grande, Christian Michael Squillante, Andrea Troxel, Mark Yarchoan
Journal: Journal of Clinical Oncology (2018)

6088 Background: CABO is a multi-tyrosine kinase inhibitor targeting VEGF receptor kinase, RET, MET and AXL. We previously participated in a Phase I study which suggested activity in the RAI-refractory DTC patients that had had one or more prior therapies. To further study the activity of CABO in differentiated thyroid cancer, we conducted a single-arm open-label phase II study of CABO in patients with metastatic, RAI-refractory DTC in the first-line setting (clinicaltirals.gov: NCT02041260). Methods: Thirty-five patients with metastatic, RAI-refractory, unresectable or locally-advanced DTC were administered CABO 60 mg orally QD. Responses were monitored by CT scan every 2 months. The primary outcome was response rate (RR) and secondary outcomes included progression-free survival (PFS), time to progression (TTP), duration of response and clinical benefit rate and safety. Results: Our study completed accrual in August 2017. As of Feb 2018, the median time on study is 35 wks (range 3-197). Median age is 65 yrs (range 45 to 84); 17 pts (49%) are male. Of the 35 total patients, 22 (63%) have papillary, 3 (9%) have Hürthle cell and 10 (29%) patients have poorly differentiated histology. Partial response (PR) was achieved in 19 (54%) patients with a median duration of response of 40 wks (range 10 to 198+). Fifteen (43%) had stable disease (SD) with a median duration of 25 wks (range 8 to 143+), and 9 (26%) maintained their SD > 6 mos for a clinical benefit rate (CR+PR+SD > 6mos) of 80% (n = 28). Median PFS has not been reached and updated PFS data will be presented. Among the six patients who progressed, the median TTP was 35 weeks. Sixteen patients remain on study as of February 2018. CABO was well tolerated with dose interruptions and dose adjustments as needed; the most common treatment-related adverse events included hyperglycemia, diarrhea, fatigue/malaise, weight loss. Conclusions: This is the first study to document CABO anti-tumor activity in patients with RAI-refractory DTC in the first-line setting. The 54% RR is comparable to currently approved agents and warrants further investigation in this patient population. Clinical trial information: NCT02041260.
Creating and developing games throughout interdisciplinarity and patient participation.
Authors: Simone Lehwess Mozzilli, Elisa Sassi, Ludmilla Rossi, Viviane Sonaglio, Fernanda Francisco, Adriana Duarte, Lisandra Panzoldo dos Santos, Gica Yabu, Simone Treiger Sredni
Journal: Journal of Clinical Oncology (2017)

e18231 Background: In an increasingly technological world, digital information about childhood cancer that is easily accessible to pediatric patients, their families and healthcare providers is still missing. In this scenario, we decided to bring all our stakeholders – patients, caregivers, healthcare professionals, creatives and entrepreneurs - together to create an application for tablet and mobile devices that would help children demystify cancer and its treatment. Methods: Materials and platforms used included: 1- Interdisciplinarity: which involves the combination of two or more academic disciplines into one activity; 2- Design Thinking: a human-centered methodology for a rapid ideation (idea generation) with the ability to visualize and adapt the results in near real-time; 3- Agile UX: a methodology which integrates the user experience design team and the developer team; 4- Patient Centered Design; 5- Project Management Platforms; 6- Collaboration and Communication Tools. Results: 1- Development of an application with 20 minigames for iOS and Android platforms, in a language that is easily accessible to children with an attractive an colorful interface where the child can identify him/herself with a custom designed character that guides them through different steps of the treatment. The initiative was highlighted in the AppStore and resulted in almost 4 million views. 2- Acquisition and expansion of interdisciplinarity for all stakeholders. 3- And most importantly, development of empathy and compassion for our patients. Conclusions: The interdisciplinarity and the effective participation of all the stakeholders in the project, allowed an integrated access to information, facilitating the understanding, identification, codification and availability of information that resulted in generation of easily accessible knowledge to our targeted population. The greatest transformation was not only in the technological advance itself, but in our new way to associate knowledge with human factors in order to educate, empower and improve the quality of life of children fighting cancer. www.beaba.org/games The app is currently available only in Portuguese, but we are raising funding to translate to other languages.
MOR202 with low-dose dexamethasone (Dex) and in combination with pomalidomide/dex and lenalidomide/dex in relapsed or refractory multiple myeloma (RRMM): Interim analysis of a phase I/IIa dose-escalation study.
Authors: Marc Raab, Manik Chatterjee, Hartmut Goldschmidt, Hermine Agis, Igor W. Blau, Hermann Einsele, Monika Martha Engelhardt, Barbara Ferstl, Martin Gramatzki, Christoph Röllig, Katja C. Weisel, Tiantom Jarutat, Dominika Weinelt, Mark Winderlich, Rainer Boxhammer, Christian Peschel
Journal: Journal of Clinical Oncology (2017)

8024 Background: CD38 is a type II transmembrane glycoprotein expressed by MM cells. MOR202, a human IgG1 CD38 monoclonal antibody, has shown high single-agent activity in preclinical models of MM and synergy in combination with immunomodulatory drugs (IMiDs), lenalidomide (LEN) and pomalidomide (POM). Methods: This interim analysis of a multicenter phase I/IIa study reports safety and efficacy data from RRMM patient (pt) cohorts treated with clinically relevant doses of MOR202 (2-hour IV infusion; 4, 8 and 16 mg/kg q1w) + Dex (≤40 mg), or at 8 or 16 mg/kg q1w with an IMiD/Dex. Primary objectives were to evaluate the safety, maximum tolerated dose (MTD) and recommended phase II dose of MOR202. Results: As of January 2017, 79 pts had been treated, including 44 in clinically relevant cohorts: 18 received MOR202 + Dex, 15 MOR202 + LEN/Dex and 11 MOR202 + POM/Dex. Pts had received a median of 3, 2 and 3 prior treatment lines, respectively. The MTD of MOR202 was not reached. Combinations were generally well tolerated, with grade ≥3 adverse events (AEs) mainly hematological; 2 pts discontinued due to a MOR202-related AE (one grade 4 thrombocytopenia; one grade 3 acute kidney failure). Infusion-related reactions (all grade 1 or 2) were seen in only 3/44 (7%) pts, and mainly occurred during the first infusion. In the MOR202 + Dex cohort, 5/17 (29%) evaluable pts (receiving at least 1 cycle of treatment) had a response, including 3 with partial responses (PRs) and 2 with very good PRs (VGPRs). Responses were also seen in 11/13 (85%, 8 PRs, 3 VGPRs) evaluable pts in the MOR202 + LEN/Dex cohort and 5/9 (56%, 2 complete responses, 3 PRs) in the MOR202 + POM/Dex cohort. Longest response duration was 17 months (MOR202/Dex). Preliminary analysis showed preservation of high CD38 levels on MM cells under MOR202 therapy. Conclusions: In heavily pretreated pts with RRMM, a 2-hour infusion of MOR202 administered at up to 16 mg/kg with Dex or in combination with an IMiD/Dex, showed a favorable safety profile, including excellent infusion tolerability. Promising preliminary efficacy and long-lasting tumor control was seen. Clinical trial information: NCT01421186.
Opportunities and Challenges in Mendelian Randomization Studies to Guide Trial Design
Authors: Christopher J. O’Donnell, Marc S. Sabatine
Journal: JAMA Cardiology (2018)

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Evaluation of overall survival (OS), progression-free survival (PFS), or time to progression (TTP) in systematic review of randomized clinical trials (RCT) in patients with metastatic breast cancer (MBC).
Authors: Terence Mukonje, Rafael Santana-Davila
Journal: Journal of Clinical Oncology (2012)

1089 Background: Limited data exists to establish if the introduction of newer agents has been associated with a trend towards an improved OS over time in women with MBC. Methods: Trough a computer-based systematic search of PubMed we identified RCT that treated patients with MBC published between 1980 and 2011. Trials that compared systemic chemotherapy for MBC, and reported a median OS were included. We excluded trials that use concomitant hormonal treatment, investigated only immunotherapy, or if they enrolled only responders to an initial regimen. The data abstracted included: year of publication, number of patients, regimens used, number of patient treated as 1 st line vs. refractory patients, median PFS, TTP and OS. Linear regression analysis was used to establish trends. Results: An initial searched revealed 5485 publications, 134 RCT that enrolled 38,090 patients fulfilled our entry criteria and were included. First line therapy was studied in 99 trials and 35 evaluated mostly refractory patients. The use of adjuvant therapy has increased substantially, trials reported in the 1980’s had a mean of 0.07% of patients having had adjuvant chemotherapy compare to a mean of 48% in the last decade. Overall survival has significantly improved; the slope of the fitted line for first line clinical trials was 0.39 (p&lt;0.001), which indicates a 0.39-month increase in median survival time per year. In trials of subsequent lines of therapy this slope was 0.19 (p=0.001). PFS or TTP was reported in 98 trials, interestingly in contrast to OS, this has not significantly changed, the slope for the fitted line has remained almost flat in both first line (0.002, p=0.97) and refractory trials (0.01, P=0.81). Conclusions: Our study is the first of its kind conducted in trials of patients with MBC. It shows that progress has been made in the last 3 decades OS in women affected with MBC, however the lack of change in PFS or TTP appears to indicate that the increase in OS is driven by a combination of newer agents, more subsequent lines of therapy being offered to patients and improved palliative care.
Timing, presentation, and patterns of failure of leptomeningeal disease after surgical resection and radiosurgery for brain metastases: A multi-institutional analysis.
Authors: Roshan Sudhir Prabhu, Scott G. Soltys, Brandon E Turner, Samuel Marcrom, John B. Fiveash, Paul M Foreman, Robert H. Press, Kirtesh R. Patel, Walter John Curran, William Breen, Paul D. Brown, Krishan Jethwa, Inga S. Grills, Jessica Arden, Lauren M Foster, Matthew A. Manning, Joseph D Stern, Anthony L. Asher, Stuart Burri
Journal: Journal of Clinical Oncology (2018)

2070 Background: Postoperative (post-op) radiosurgery (SRS) has been proposed as a standard of care based on 2 phase III trials, but has been associated with up to 30% risk of leptomeningeal disease (LMD). The specifics of timing, presentation, and patterns of LMD failure have not been well described. Methods: The records of patients (pts) with brain metastases (BM), of which 1 was resected and treated with post-op or pre-op SRS, and who subsequently developed LMD were combined from 7 tertiary care centers. Pts with classically radiosensitive tumors or prior or planned whole brain radiotherapy were excluded. LMD pattern was categorized as either nodular or linear (“sugarcoating”). Results: The study cohort consisted of 147 pts. The most common primary sites were lung (40%), breast (24%), and melanoma (16%), and most pts received post-op SRS (94%). Pts with breast primary were enriched for HER-2 positivity (60%). The majority of resected BM (82%) extended to within 5 mm of the pial surface. Median time from initial SRS to 1st LMD was 5.6 months (interquartile range [IQR] 3.2 – 11). The majority of LMD events were nodular (60%), of which 64% were within 5 cm of the surgical corridor. The median number of nodules was 2 (IQR 1 – 4), with a median distance of 2.5 cm from the surgical corridor (IQR 1.1 – 5.2). Most pts (60%) were symptomatic at time of LMD diagnosis, of which the most common symptoms were headache (58%), cranial nerve deficit (28%), and dizziness/balance issues (24%). Of the pts who received LMD treatment and had follow-up imaging (n = 101), 50% experienced 2nd LMD at a median of 5.5 months after 1st LMD (IQR 2.8 – 9.4). Of these, 68% were symptomatic at the time of 2nd LMD diagnosis, 58% had nodular LMD with a median of 1 nodule (IQR 1-3), and 70% underwent salvage therapy. Conclusions: LMD failure is an increasingly recognized event after surgery and SRS for BM. Pts who experience LMD are enriched in HER-2 positive disease and superficial location of the resected BM. Nodular LMD is the predominant pattern of LMD failure in this pt population, with most LMD events being symptomatic. 2nd LMD is common after initial salvage therapy and also has a predominantly nodular pattern.
Effect of MCAM on the aggressive phenotype in human prostate cancer.
Authors: Marianna Kruithof-de Julio, Eugenio Zoni, Letizia Astrologo, Janine Melsen, Irena Klima, Joel Grosjean, Gabri Van der Pluijm, George N. Thalmann
Journal: Journal of Clinical Oncology (2017)

e23135 Background: Prostate Cancer (PCa) is the most common cancer in males and the second leading cause of death from cancer in men. Understanding the factors that regulate homing and survival of metastatic cancer cells in the bone is important for the identification of new therapeutic targets. High MCAM expression has been detected in the stroma of lytic and blastic lesions in preclinical models of PCa bone metastasis. The objective of this study is to characterize the role of MCAM in the maintenance of the aggressive phenotype in human PCa. Methods: We knocked and down MCAM in the lytic PC-3M-Pro4Luc2_dTomato and in the blastic C4-2B_dTomato PCa cell lines. Validation was done at both protein and RNA level. We performed functional assays such as migration and proliferation. RT-qPCR was used to test MCAM knockdown on EMT markers. The effect of the knockdown on the maintenance of cancer stem/progenitor-like cells was measured by ALDEFLUOR. Results: MCAM knockdown reduced proliferation in PC-3M-Pro4Luc2_dTomato PCa cells and resulted in increased E-Cadherin expression. Metastatic human PCa cells target the hematopoietic stem cell (HSC) niche in the bone marrow at the level of an “endosteal/osteoblast” niche and a “vascular/perivascular” niche. We set-up an in vitro model of “osteoblast niche” to study the prostate cancer cells upon co-culture with osteoblasts and to determine the effects on cancer stem/progenitor-like markers. We found that MCAM is required for the osteoblast-mediated induction of ALDH activity on PCa cells and MCAM knockdown prevented the increase in the size of the ALDH high subpopulation in PC-3M-Pro4Luc2_dTomato, mediated by human osteoblasts. Additionally, MCAM knockdown in PCa cells co-culture with osteoblast, prevented the induction of MCAM expression by osteoblasts. Finally, MCAM is significantly increased in the ALDH high cells and identifies a new subset of ALDH high / MCAM high cells which could be depleted upon MCAM knockdown. Conclusions: We detected a new subset of ALDH high /MCAM high cells and demonstrated the MCAM influences the maintenance of an aggressive-mesenchymal phenotype in human PCa. Therefore, MCAM represent an interesting target molecule to modulate the behavior of aggressive PCa cells.
Concordance between RTOG and EORTC risk factors in low grade gliomas: Who will remain standing in the ring at bell’s sound?
Authors: Enrico Franceschi, Antonella Mura, Alexandro Paccapelo, Stefania Bartolini, Santino Minichillo, Andrea Lanese, Raffaele Agati, Damiano Balestrini, Maria Francesca Currà, Chiara Scafati, Michela Visani, Monica Di Battista, Laura Lombardo, Giovenzio Genestreti, Alba Ariela Brandes
Journal: Journal of Clinical Oncology (2018)

2040 Background: Low grade gliomas (LGG) are a heterogeneous group of brain primary tumors. The EORTC and the RTOG criteria are the most valuable scores to evaluate risk factors and for treatment decision. However, there is no data about concordance between criteria. Methods: We conducted an analysis on LGG patients treated in our Institution from 1998 to 2015. The population was stratified by RTOG criteria and whenever feasible we assessed the risk using both RTOG and EORTC criteria. Results: Median follow up (mFU) was 78.6 months. We evaluated 204 patients with histologically diagnosed LGG. All the patients were stratified by RTOG criteria and a subgroup of 51 patients by both RTOG and EORTC criteria. The univariate analysis showed a statistically significant difference according to RTOG criteria (p = 0.01) for both OS and PFS. Low risk patients had a better OS compared to high risk group (211.0 vs 145.5 months, p = 0.01) and a longer PFS (60.0 vs 39.8 months, p = 0.005). The multivariate analysis confirmed that RTOG risk was an independent prognostic factor (p = 0,024). In the subgroup of 51 patients stratified by both RTOG and EORTC risk-factor criteria, the concordance was 54.9% (K = 0.113, p = 0.08). All the EORTC high risk patients (n = 25) were high risk also with RTOG criteria. Among the 26 EORTC low risk patients, only 3 (11.5%) were low risk with RTOG criteria, while 23 (88.5%) would have been deemed as high risk. In this population, after a FU or 91 months, no statistical difference regarding OS and PFS was documented applying either RTOG or EORTC criteria, probably due to the limited population. Conclusions: The concordance between RTOG and EORTC criteria is low, especially in the evaluation of low risk patients. So far, we cannot compare clinical trials adopting different risk criteria.
P01.016 Caregiver Burden and Distress in Newly Diagnosed Gliomas: A Prospective Analysis
Authors: L Hemminger, C Ibegbu, J Serventi, J Burke, J Occhiogrosso, N Mohile
Journal: Neuro-Oncology (2018)

Understanding the caregiver experience in gliomas is critical due to cognitive dysfunction and physical dependence. Caregiver burden, quality of life and distress for this population is not well described. We performed an IRB-approved prospective study of 100 caregivers of patients with newly diagnosed gliomas enrolled over 2.5 years at a single academic institution. Caregivers were defined as individuals responsible for any aspect of patient support. Caregivers completed the Caregiver Quality of Life in Cancer (CQOLC) survey and questions about time required for patient care at 3 time points: initial diagnosis, 3 mo. and 6 mo. post-diagnosis. We described change in overall caregiver distress (CQOLC) and time spent on patient care, and also described the association between CQOLC scores and time required for patient care. 76/100 caregivers completed a survey for at least 1 time point: 65/100 at initial diagnosis, 43/100 at 3 mo. and 37/100 at 6 mo. The 76 caregivers (56 female) included 50 spouses, 13 children, 8 parents, 3 siblings and 2 friends. 58 were primary caregivers. Patients’ diagnoses included: 60 glioblastoma, 12 anaplastic astrocytoma, and 4 low grade glioma. Mean CQOLC scores did not significantly change from initial diagnosis (55.9) to 3 mo. (52.8) and 6 mo. (59.7) post-diagnosis (p-value = 0.56, 0.28, and 0.22 respectively). The proportion of caregivers spending >20 hrs/week on direct patient care did not significantly change from initial diagnosis (50%) to 3 mo. (47%) and 6 mo. (43%) post-diagnosis (p-value = 0.76, 0.50, and 0.66 respectively). At initial diagnosis, caregivers who spent >20 hrs/week on direct patient care had a significantly higher distress score on the CQOLC than those who spent <20 hrs/week on patient care (p = 0.0008). This is also true at 3 mo. post-diagnosis (p =0.015), but not at 6 mo. post-diagnosis (p =0.09). Caregiver distress and time burden is substantial even at the time of diagnosis, and does not diminish over the first 6 mo. after diagnosis. Caregivers who spend more time on direct patient care have higher levels of distress at initial diagnosis and 3 mo. post-diagnosis, but not at 6 mo. post-diagnosis. Early interventions to help caregivers cope with time burden and minimize distress are needed.
Detection of <i>EGFR</i> mutations in NSCLC patients in clinical practice: Comparison between cobas and Scorpion ARMS method.
Authors: Natsuki Takano, Satoru Kitazono, Ryo Ariyasu, Junji Koyama, Masafumi Saiki, Tomoaki Sonoda, Yosuke Kawashima, Tomoyo Oguri, Shingo Nishikawa, Noriko Yanagitani, Fumiyoshi Ohyanagi, Atsushi Horiike, Takeshi Horai, Makoto Nishio
Journal: Journal of Clinical Oncology (2017)

e23101 Background: Epidermal growth factor receptor (EGFR) mutation is the most important factor for determining the treatment strategy for non-small-cell lung cancers (NSCLCs). Currently, two methods (cobas and Scorpion ARMS) have been approved as companion diagnostics for using EGFR tyrosine kinase inhibitor (TKI). Although there are some differences in the spectrums and sensitivities for detecting EGFRmutations such as exon 19 deletions (ex19del), L858R and T790M mutations, the extent of the differences affecting clinical practice is unclear. Methods: All patients with NSCLC who underwent EGFR mutation tests and treated at our hospital from February 2014 to February 2016 were enrolled. To detect EGFR mutations, the Scorpion ARMS (S) method was used from 2014 to 2015 and thecobasEGFR Mutation Test (C) from 2015 to 2016. We retrospectively investigated the detection rate of each EGFRmutation type and compared the rates between the two methods. Results: A total of 1,287 patients were enrolled. To detect EGFR mutations, 627 patients were tested by the S method and 660 by the C method, respectively. Of 1287 patients, 910 patients underwent initial biopsy, whereas 121 patients underwent re-biopsy after EGFR-TKI failure. EGFRmutations were detected in 130 of 418 (31.1%) patients and 153 of 492 (31.1%) patients by the S and C methods, respectively in the initial biopsy (P = 0.982). However, the detection rate of ex19del was slightly lower in the S method (12.6%) than in the C method (16.3%) (P = 0.105). Conversely, the detection rate of L858R was lower in the C method (13.8%) than in the S method (16.7%), but the difference was not significant (P = 0.252). De novo T790M was detected in one (0.2%) patient by the S method and in none by the C method. In re-biopsy after EGFR-TKI failure, the detection rates of T790M were as follows: 19 of 55 patients (34.5%) by the S method and 20 of 66 (30.3%) by the C method (P = 0.619). Conclusions: The different spectrums and sensitivities of EGFR mutations between the S and C methods were observed; however, they did not significantly affect clinical practice.