tbuckley/cabot-search huggingface dataset:
P01.051 Imaging based analysis of changes in grey and white matter in glioblastoma patients treated with tumor treating fields
Authors: M A Proescholdt, A Rzepus, A Haj, C Doenitz, A Brawanski, K Rosengarth
Journal: Neuro-Oncology (2018)

After a positive randomized clinical trial showing significant survival benefits, Tumor Treating Fields (TTFields) have been implemented in the management of newly diagnosed glioblastoma (GBM). Biophysical modeling of TTField application has demonstrated a heterogeneous electric field distribution within the intracranial space, reaching maximal intensities at tissue borders with different electric conductivity. However, no imaging modality is available to visualize the impact of TTField treatment within the tumor and the bordering normal brain in each individual patient. Our hypothesis is that the distribution and field intensity may be highly heterogeneous between GBM patients depending on tumor size, resection status and perifocal edema. The goal of our study is to develop a voxel based imaging analysis tool, which may allow to detect specific changes induced by TTFields in GBM patients. Structural MR-Data of 27 patients suffering from newly diagnosed GBM treated according to the Stupp protocol combined with TTFields and 27 control patients (matched for gender, age, IDH1 mutation and MGMT promoter methylation status) treated according to the Stupp protocol without TTFields. Imaging acquisition was conducted at 1.5 T MRI-Scanners at the Department of Neuroradiology of the University Regensburg Medical Center. For both patients groups a high-resolution T1-weigthed image (3D magnetization prepared rapid gradient echo) was acquired during disease control after the concomitant phase and after the first two cycles of adjuvant chemotherapy either with or without TTField treatment. To analyze group and therapy-induced longitudinal differences of grey and white matter density, individual MRI-T1-data sets were preprocessed using the (V)oxel (b)ased (M)orphmetry and D(iffeomorphic) A(natomical) R(egistration) T(hrough) E(xponentiated) L(ie) A(lgebra) toolboxes both implemented in (S)tatistical (P)arametric (M)apping 12 running under MaTLab R2016b. Possible group differences were subsequently assessed by parametric t-test for independent samples as well as within subject’s t-tests for determination of longitudinal therapy-inducing effects. The study has received a positive vote from the Ethical Board of the University Regensburg Medical Center. The first patients are being recruited, the actual results will be evaluated and presented during the meeting.
Dabrafenib plus trametinib (D + T) as adjuvant treatment of resected <i>BRAF</i>-mutant stage III melanoma: Findings from the COMBI-AD trial analyzed based on AJCC 8 classification.
Authors: James M. G. Larkin, Axel Hauschild, Mario Santinami, Victoria Atkinson, Mario Mandalà, Vanna Chiarion-Sileni, Marta Nyakas, Caroline Dutriaux, Andrew Haydon, Laurent Mortier, Caroline Robert, Jacob Schachter, Dirk Schadendorf, Ran Ji, Paola Aimone, Bijoyesh Mookerjee, Richard Kefford, Reinhard Dummer, John M. Kirkwood, Georgina V. Long
Journal: Journal of Clinical Oncology (2018)

9591 Background: The COMBI-AD trial demonstrated that adjuvant treatment with D + T in patients (pts) with resected stage III BRAF-mutant melanoma significantly reduced the risk of melanoma recurrence vs placebo (pbo). Pts were stratified based on the AJCC 7 disease stage classification. We present efficacy results from COMBI-AD based on the updated AJCC 8 staging classification. Methods: COMBI-AD (NCT01682083) is a randomized, double-blind, pbo-controlled, phase 3 study evaluating pts with stage III BRAF V600E/K–mutant melanoma without prior anticancer therapy. Pts were randomized 1:1 within 12 weeks of complete resection to receive D 150 mg twice daily plus T 2 mg once daily or matching pbos for 12 months. The primary endpoint was relapse-free survival (RFS). Pts were stratified by disease stage (stages IIIA, IIIB, and IIIC) based on AJCC 7 criteria. This post hoc subgroup analysis evaluated RFS in pts by disease stage based on AJCC 8 (stages IIIA, IIIB, IIIC, and IIID). Results: 870 pts were randomized (D + T, n = 438; pbo, n = 432). Pts were recategorized per AJCC 8 into stages IIIA (D + T, n = 50; pbo, n = 39), IIIB (D + T, n = 145; pbo, n = 154), IIIC (D + T, n = 217; pbo, n = 214), and IIID (D + T, n = 22; pbo, n = 17). RFS benefit with D + T over pbo was observed regardless of disease stage (stage IIIA: HR, 0.46 [95% CI, 0.17-1.21]; stage IIIB: HR, 0.46 [95% CI, 0.33-0.65]; stage IIIC: HR, 0.49 [95% CI, 0.38-0.64]), with the largest benefit observed in higher-risk stage IIID pts (HR, 0.34 [95% CI, 0.15-0.80]). When stage IIIB and IIIC subgroups were combined, the HR for RFS (D + T vs pbo) was the same (0.48) regardless of the AJCC classification used. Three-year RFS rates favored pts in the D + T vs pbo arm across all disease stages: IIIA, 83% vs 70%; IIIB, 63% vs 43%; IIIC, 52% vs 33%; and IIID, 40% vs 18%. RFS rates were similar in D + T and pbo arms in pts with stages IIIA, IIIB, and IIIC disease whether classified by AJCC 7 or 8. Conclusions: The RFS benefit observed with D + T vs pbo in pts with resected BRAF V600E/K–mutant melanoma was similar across all stages and was maintained when reclassified by AJCC 8 compared with the original AJCC 7 classification. Clinical trial information: NCT01682083.
Using mobile and sensor technology to identify early dehydration risk in head and neck cancer patients undergoing radiation treatment: Impact on symptoms.
Authors: Susan K. Peterson, Adam S. Garden, Eileen H. Shinn, Sanjay Shete, Stephanie L. Martch, Maria Camero, George Baum, Emilia Farcas, Kai Lin, Frederic Raab, Viswanath Nandigam, Yan Yan, Renata Ferrarotto, Job Godino, Kevin Patrick, Beth Michelle Beadle
Journal: Journal of Clinical Oncology (2018)

6063 Background: Assessment and intervention with mobile and sensor technology may improve early detection and mitigation of treatment-related symptoms, impact quality of life (QOL), reduce complications, and lower health care costs. The CYCORE (CYberinfrastructure for COmparative effectiveness Research) system utilizes sensor and mobile technology to remotely assess daily weight, blood pressure (BP)/pulse, and patient-reported outcomes in head and neck cancer (HNC) patients undergoing radiation treatment (RT). Clinicians reviewed data daily to identify early risk of dehydration and support early intervention to improve symptom management. We compared longitudinal symptom data in patients randomized to use CYCORE during RT versus those randomized to usual care. Methods: Methods: HNC patients (n = 357) completed the 28-item MD Anderson Symptom Inventory (MDASI) at RT initiation (baseline), completion of RT (6-7 weeks post-baseline), and 6-8 weeks post-RT completion. Symptom severity and interference were rated on 0-10 scales; lower scores indicated better outcomes. Repeated measures ANOVA evaluated time point and group differences in MDASI scores. Results: Mean age was 60 years (range 25-86), 21% were female, 85% were White, and 54% completed college. Baseline MDASI mean scores were similar in patients randomized to CYCORE (n = 169) or usual care (n = 188). Mean scores on the severity of general and HNC-specific symptoms were lower in the CYCORE versus usual care group at completion of RT (2.92 vs. 3.4, p = .003; 4.21 vs 4.83, p = .009), and at 6-8 weeks post-RT completion (1.69 vs 1.96; p = .003; 1.78 vs. 2.11, p = .009). Mean scores on symptom interference in daily life were similar in both groups across time. Conclusions: HNC patients randomized to the CYCORE group during RT self-reported lower severity of general and HNC-specific symptoms compared to usual care. Sensor and mobile technology can enable monitoring of patients’ symptoms and related outcomes during critical periods of outpatient cancer treatment, can provide timely information to facilitate rapid clinical decision making about care, and may ultimately result in better QOL and health outcomes. Clinical trial information: NCT02253238.
Is metronomic vinorelbine (mVRL) able to inhibit both HUVEC and triple-negative breast cancer (TNBC) cells? The proof-of-concept VICTOR-0 study.
Authors: Maria Grazia Cerrito, Davide Pelizzoni, Marco De Giorgi, Nunzio Digiacomo, Marialuisa Lavitrano, Roberto Giovannoni, Paolo Bidoli, Marina Elena Cazzaniga
Journal: Journal of Clinical Oncology (2017)

e14014 Background: TNBC represents an important clinical challenge because of poor prognosis. One of the emerging strategy to achieve disease control while reducing toxicity is metronomic chemotherapy (mCHT) which targets the endothelial cells (ECs) and inhibits the tumor growth. mVRL is a promising option in patients (pts) with metastatic breast cancer (MBC), resulting in a median PFS of 7.7 months and median OS of 15.9. To better explain the effect of mVRL we studied the effects of metronomic doses of VRL in in vitro models and compared them with standard doses of the same drug. Methods: Cell viability and cytotoxicity assays were performed on TNBC cancer cells (MDA-MB-231) and Human Umbilical Vein Endothelial Cells (HUVEC). Cell lines were exposed to different concentration (0,01nM-1mM) of VRL for 4 and 96 h. To simulate the metronomic dosing schedule, we replaced the drug-enriched medium every 24h, while to simulate the conventional administration protocol (sCHT) cells were exposed to VRL for 4h, then the medium was changed and replaced with fresh medium without drug every 24 h. The IC 50 was calculated by non-linear regression fit of the mean values of data obtained in triplicate experiments. Results: A significant anti-proliferative activity was observed on both HUVEC and MDA cells treated with VRL in mCHT as compared to sCHT protocol (see Table). These lower drug concentrations did not have remarkable effects on cell death. Conversely, the higher dose utilized in sCHT produced important cell death in MDA as well as in HUVEC, even if in vivo, the higher dose of drug inducing the largest apoptosis of cancer cells also affectd healthy proliferating cells causing toxicity. Our findings suggest that mCHT inhibited the proliferation of both endothelial and tumour cells and can block cancer progression with minor side effects. Conclusions: This study provides the proof-of-concept that metronomic doses of VRL, but not the standard ones, are able to inhibit, at the same concentration, both the ECs and the TNBC cells. The clinical trial TEMPO-BREAST, which compares metronomic vs standard VRL, is ongoing in MBC pts. [Table: see text]
Long-term outcomes after sublobar resection for clinical stage IA lung adenocarcinoma meeting node-negative criteria defined by HRCT and FDG-PET/CT.
Authors: Yasuhiro Tsutani, Haruhiko Nakayama, Takuro Tasaki, Hideaki Hanaki, Hiroyuki Ito, Yoshihiro Miyata, Morihito Okada
Journal: Journal of Clinical Oncology (2018)

8554 Background: The purpose of this study is to evaluate long-term outcomes after sublobar resection for patients with clinical stage IA lung adenocarcinoma meeting our proposed node-negative (N0) criteria: solid component size of less than 0.8 cm on HRCT or SUVmax of less than 1.5 on FDG-PET/CT. Methods: Between April 2006 and December 2010, 347 patients with clinical stage IA lung adenocarcinoma underwent complete resection after preoperative HRCT and FDG-PET/CT in Kanagawa Cancer Center and Hiroshima University. Long-term outcomes of patients who met the N0 criteria after sublobar resection were evaluated. Results: Two-hundred one (57.9%) patients met the N0 criteria. Patients who met the N0 criteria were significantly associated with low grade adenocarcinoma subtype (adenocarcinoma in situ, minimally invasive adenocarcinoma, or lepidic adenocarcinoma; P < 0.001), negative lymphatic invasion (P < 0.001), negative vascular invasion (P < 0.001), and negative pleural invasion (P < 0.001). One of 201 (0.5%) patients had lymph node metastasis. The median follow-up period was 86.1 months. There was significant difference in overall survival (OS) between patients who met the N0 criteria (5-year OS rate, 93.9%; 10-year OS rate, 90.3%) and those who did not meet the N0 criteria (5-year OS rate, 81.5%; 10-year OS rate, 64.3%; P < 0.001). In patients who met the N0 criteria, there was no significant difference in OS between patients who underwent lobectomy (5-year OS rate, 94.3%; 10-year OS rate, 92.6%) and those who underwent sublobar resection (5-year OS rate, 93.8%; 10-year OS rate, 89.3%; P = 0.640). Conclusions: Sublobar resection is feasible for clinical stage IA lung adenocarcinoma meeting N0 criteria defined by HRCT and FDG-PET/CT with excellent long-term survival.
Detection, molecular profiling and culture of CSF-CTCs in leptomeningeal disease (LMDz) in melanoma.
Authors: Peter A. J. Forsyth, Brittany Evernden, Vincent Law, Rajappa Kenchappa, John Puskas, Elena Ryzhova, Inna Smalley, Nam D. Tran, Arnold B Etame, Solmaz Sahebjam, Anthony Martin Magliocco, Keiran Smalley
Journal: Journal of Clinical Oncology (2018)

e21543 Background: Approx. 5% of melanoma-associated brain tumor cases also develop LMDz. Patients with LMDz have devastating survival outcome, and currently there is no effective treatment. The aim of this study was to determine whether diagnosis and personalized treatment for melanoma-LMDz could be improved using the Veridex CellSearch System adapted to enumerate CTCs from CSF. Cell-free DNA (cfDNA) and cell-associated DNA (caDNA) were analyzed. Culturing conditions were optimized for CSF-CTCs expansion ex vivo. Methods: Peripheral blood (PB)/CSF-CTCs were detected by Veridex CellSearch System and the circulating melanoma cell kit. Melanoma cell enrichment and detection was based on anti-CD146 and anti-high molecular weight melanoma associated antigen (HMW-MAA-PE (MEL-PE)). Anti-CD34-APC was used for ruling out endothelial cells, anti-CD45-APC was used for ruling out leukocytes and DAPI was used for nuclear staining. Both cfDNA and caDNA were extracted and sequenced with TruSight Tumor 26 panel, Illumina Inc and then profiled in Mela Carta MassArray System. Results: PB-CTCs & CSF-CTCs: 12 patients with definite LMDz and 8 melanoma patients without LMDz were studied. Of the 12 LMDz patients, all but 1 patient (92%) had CSF-CTCs (range, 23 CTCs/ml CSF to 3055 CTCs/ml CSF). 3 of 12 patients (25%) had PB-CTCs, ranging from 0.4 CTCS/ml PB to 6.5 CTCs/ml PB. In contrast, only 3 of 8 (37%) melanoma patients without LMDz had CSF-CTCs detected, with significantly lower number of CTCs per ml CSF, ranging from 0.13 CTCs/ml CSF to 0.6 CTCs/ml CSF. In their PB, 2 of 8 patients (25%) had PB-CTCs, ranging from 0.5 CTCs/ml PB to 1.6 CTCs/ml PB. Profiling of CSF-CTCs: LMDz patients showed GNAQ Q209P mutation (uveal melanoma), NRAS Q61R mutation (nasal melanoma) and also BRAF V600E mutation. Ex vivo culture of CSF-CTCs: We successfully demonstrated ex vivo expansion of isolated CSF-CTCs is possible for ~25% of samples. Cells were cultured in growth medium supplemented with FBS, EGF and FGF. Conclusions: Taken together, the results indicate the potential value of CSF as a biopsy surrogate for assessing genetic makeup of CSF malignancies. CSF-CTCs can be cultured ex vivo and used as valuable reagent for studying the biology of LMDz.
IMMUNOSARC: A collaborative Spanish (GEIS) and Italian (ISG) Sarcoma Groups phase I/II trial of sunitinib plus nivolumab in selected bone and soft tissue sarcoma subtypes—Results of the phase I part.
Authors: Javier Martin Broto, Nadia Hindi, Andres Redondo, Javier Martinez-Trufero, Silvia Stacchiotti, Emanuela Palmerini, Enrique Alava, David Silva Moura, Herminia Perez Vega, Irene Otero, Patricio Ledesma, Emanuela Marchesi, Jose A. Lopez-Martin
Journal: Journal of Clinical Oncology (2018)

11515 Background: Disruption of angiogenesis substantially enhances the efficacy of immune-based cancer therapies. The combination of an antiangiogenic drug (sunitinib or pazopanib) plus anti- PD1 (nivolumab) exhibited both higher activity and toxicity compared with antiangiogenic drug alone in renal cell carcinoma (RCC). We hypothesized that sunitinib (SU) and nivolumab (NI) could be synergistic in some sarcoma subtypes and the toxicity profile could be different from RCC. We present the results of phase I part of the combination of SU-NI in advanced sarcoma patients (pts). Methods: Pretreated progressing pts, ECOG 0-1 and diagnosed with UPS, synovial sarcoma (SS), clear cell sarcoma (CCS), angiosarcoma (AS), epithelioid hemangioendothelioma (EH), solitary fibrous tumor (SFT), epithelioid sarcoma (ES), osteosarcoma (OS), Ewing sarcoma (EWS) or dedifferentiated chondrosarcoma (DCh) were eligible. SU 37.5 mg/d as induction was given for the first 14 days. The dose-finding stage (from day 15 to 45) would be completed when 10 dose limiting toxicity (DLT)-evaluated pts had been treated with DLT rate < 0.33. Two level- doses were designed: (0 initial) SU 37.5 mg/d or (-1) SU 25 mg/d along with NI 3 mg/kg/2w for both. SU-NI was maintained up to progression or intolerance. Results: From May to October 2017, 16 pts (M/F 10/6), median age 38y (25-78) were enrolled. Diagnosis was: CSS in 4 (25%), ASPS in 3 (19%); AS, OS, SS (2 each, 12.5%); UPS, extraskeletal OS and Ch (1 each, 6%). There were three DLT in the first 6 pts at dose level 0 (G3 fatigue in 2 and G4 septic shock) and 1 DLT in the following 10 pts at level -1 (febrile neutropenia). G3/4 toxicity: fatigue 25%, thrombocytopenia 19%, mucositis 13% and neutropenia 13%. There were 6 RECIST PR (42.8%), 4 SD (2 of them 25% of shrinkage) and 4 PD in 14 evaluable pts. PR occurred in 2 CCS and in one of AS, Ch, SS, ASPS while 2 cases (ASPS and UPS) shrank 25%. Conclusions: At the RDP2 (SU 25 mg/d and NI 3 mg/kg/2w), SU-NI is a feasible combination with manageable toxicity. SU-NI has induced objective responses in several sarcoma subtypes. The study is currently on a phase II part. Clinical trial information: NCT03277924.
Trial of Fingolimod versus Interferon Beta-1a in Pediatric Multiple Sclerosis
Authors: Tanuja Chitnis, Douglas L. Arnold, Brenda Banwell, Wolfgang Brück, Angelo Ghezzi, Gavin Giovannoni, Benjamin Greenberg, Lauren Krupp, Kevin Rostásy, Marc Tardieu, Emmanuelle Waubant, Jerry S. Wolinsky, Amit Bar-Or, Tracy Stites, Yu Chen, Norman Putzki, Martin Merschhemke, Jutta Gärtner
Journal: New England Journal of Medicine (2018)

Treatment of patients younger than 18 years of age with multiple sclerosis has not been adequately examined in randomized trials. We compared fingolimod with interferon beta-1a in this population.In this phase 3 trial, we randomly assigned patients 10 to 17 years of age with relapsing multiple sclerosis in a 1:1 ratio to receive oral fingolimod at a dose of 0.5 mg per day (0.25 mg per day for patients with a body weight of ≤40 kg) or intramuscular interferon beta-1a at a dose of 30 μg per week for up to 2 years. The primary end point was the annualized relapse rate.Of a total of 215 patients, 107 were assigned to fingolimod and 108 to interferon beta-1a. The mean age of the patients was 15.3 years. Among all patients, there was a mean of 2.4 relapses during the preceding 2 years. The adjusted annualized relapse rate was 0.12 with fingolimod and 0.67 with interferon beta-1a (absolute difference, 0.55 relapses; relative difference, 82%; P<0.001). The key secondary end point of the annualized rate of new or newly enlarged lesions on T2-weighted magnetic resonance imaging (MRI) was 4.39 with fingolimod and 9.27 with interferon beta-1a (absolute difference, 4.88 lesions; relative difference, 53%; P<0.001). Adverse events, excluding relapses of multiple sclerosis, occurred in 88.8% of patients who received fingolimod and 95.3% of those who received interferon beta-1a. Serious adverse events occurred in 18 patients (16.8%) in the fingolimod group and included seizures (in 4 patients), infection (in 4 patients), and leukopenia (in 2 patients). Serious adverse events occurred in 7 patients (6.5%) in the interferon beta-1a group and included infection (in 2 patients) and supraventricular tachycardia (in 1 patient).Among pediatric patients with relapsing multiple sclerosis, fingolimod was associated with a lower rate of relapse and less accumulation of lesions on MRI over a 2-year period than interferon beta-1a but was associated with a higher rate of serious adverse events. Longer studies are required to determine the durability and safety of fingolimod in pediatric multiple sclerosis. (Funded by Novartis Pharma; PARADIGMS ClinicalTrials.gov number, NCT01892722 .).
The establishment of a new medical model for tumor treatment combined with Watson for Oncology, MDT and patient involvement.
Authors: Juemin Fang, Zhongzheng Zhu, Hui Wang, Fei Hu, Zhuqing Liu, Xianling Guo, Jianhua Chen, Chunyan Li, Yuping Shen, Qing Xu
Journal: Journal of Clinical Oncology (2018)

e18504 Background: Watson for Oncology (WFO) is a cognitive computing system developed by IBM to assist in tumor therapy which was trained by the Memorial Sloan Caitlin Cancer Center (MSKCC) for four years. It helps the oncologists or clinic team make therapeutic decisions by providing evidence-based treatment options or recommendations with priority and personality. There have been some reports that recommendations provided by WFO and oncologists are highly consistent. Therefore, WFO may become an important tool to help oncologists make treatment options. Methods: A new cancer treatment model combined with WFO, MDT(Multiple Disciplinary Team) and patient's participation was established in Shanghai Tenth People's Hospital. At first, evidence-based, personalized, and prioritized treatment options would be given by WFO. After the discussion of MDT team, we will explain the current disease status to patients and give our options for future treatment which we think are best and most suitable for patients combined with WFO's recommendations. Results: Through a series of questionnaire surveys into doctors and patients, we found that firstly, the WFO and MDT expert teams gave highly consistent recommendations in some tumors, such as colorectal cancer, lung cancer, ovarian cancer etc. Secondly, treatment options given by MDT discussion after taking WFO recommendations into consideration were more standardized, more reasonable and more personalized. Thirdly, patients were fully involved and more engaged in the decision-making of their own treatment program. Patients had a better understanding of their own disease and more confidence in the treatment plan. They cooperated with doctors more actively. Fourth, this model promotes the promotion of standard treatment of malignant tumor, enhances the participation of MDT team, and improves the doctor-patient relationship in our hospital. Conclusions: The new model combined with human brain, Artificial intelligence (AI) and cancer patients enrichs the traditional MDT model. It is a new kind of medical model which is more effective. We hope this new medical model can be applied in more hospitals in China to improve the efficiency of tumor treatment.