tbuckley/cabot-search huggingface dataset:
Capecitabine and temozolomide (CAPTEM) for intermediate to high grade metastatic neuroendocrine tumours (NET): A single centre experience.
Authors: Arvind Sahu, Michael Jefford, Rodney J Hicks, Michael Michael
Journal: Journal of Clinical Oncology (2018)

e16159 Background: The CAPTEM regimen has significant activity in well differentiated pancreatic NETs. There is limited data regarding CAPTEM in patients (pts) with intermediate to high grade NETs. The present audit was aimed to assess functional imaging response and survival in this group. Methods: Retrospective audit of pts with metastatic grade 2 or grade 3 NETs who received capecitabine at 750 mg/m2 orally b.i.d days 1–14 and TMZ 100 mg/m2 b.i.d days 10–14 of a 28-day cycle at Peter MacCallum Cancer Centre between March 2013 and March 2017. Results: Thirty two pts received CAPTEM: 21 (66%) grade 2 differentiation and 11 (34%) Grade 3 differentiation (7 had tumours with Ki 67 < 55%, 4 with Ki67 ≥ 55%). Primary site was gastroenteropancreatic in 53%, lung in 37.5% and unknown 9.4%. The median number of metastatic sites was 3. The most common sites of metastasis included liver (n = 23, 72%), bones (n = 20, 62%), lymph nodes (n = 20, 62%) and lung (n = 13, 41%). CAPTEM was first line therapy in 22% while 37.5% had received more than 2 lines of therapy. Prior PRRT was in 22%. Median number of cycles received was 6. Complete FDG PET metabolic response seen in 12.5% while 34.4% had a partial metabolic response and 15.6% stable disease. Median follow up duration was 31 months. The 2 yr overall survival (OS) of the whole cohort was 42 % with a median OS of 24 months. The median PFS for pts with Grade 2 NET was longer than grade 3 NET but not statistically different (10 months vs 5 months; p value – 0.346). There was a trend towards improved PFS in pts with low grade 3 (Ki 67 < 55% - 15 months) compared to high grade 3 (Ki67 ≥ 55% - 4 months) (p value – 0.11). Grade 3 or 4 toxicity was seen in 10 pts (31.3%) with nausea in 5 (15.6%), thrombocytopenia 4 (12.5%), fatigue 3 (9.4%), anemia 3 (9.4%), febrile neutropenia 3 (9.4%), diarrhoea 2 (6.3%), vomiting 1 (3.1%) and mucositis 1 (3.1%). There was no grade 3 or 4 hand foot syndrome seen. Conclusions: The encouraging results of CAPTEM in a subgroup of pts with grade 3 (Ki 67 < 55%) metastatic NET should be further evaluated in a randomized trial.
Online education needs and preferences of patients with cancer and their caregivers.
Authors: Tara Herrmann, Pamela M. Peters, Emily Sherene Van Laar
Journal: Journal of Clinical Oncology (2017)

e21669 Background: Patients and caregivers have many questions upon receiving a diagnosis of cancer. One way to help alleviate this burden, and enable participation in care is through education. Patient education correlates with higher levels of satisfaction and improved clinical outcomes. However, little is known about how patients and caregivers define their education needs. Methods: We surveyed patients with cancer and caregivers to assess their perceived education needs and resources. Results:2327 individuals representing 9 malignancies participated in the survey. Participants were predominantly patients (72%), with a majority (51%) having received their initial diagnosis of cancer within the past 2 years. Less than a quarter (22%) of respondents felt their educational needs were being completely met by available resources. Respondents were most likely to seek out information at the time of diagnosis (24%) and to increase understanding of treatment options (24%). Conversely, individuals were least likely to seek education upon disease progression (7%). In all malignancies examined, the 2 topics considered most important were treatment options (70%-89%) and understanding test results (74%-87%) while information about how to take medication as prescribed was deemed least important (46%-67%). Conclusions: Our study identified a lack of educational materials available and designed to meet cancer patients’ needs on the internet. Given that few patients and caregivers reported that their educational needs are being met, efforts may be needed to ensure that those patients who want to receive education to become informed patients can find what they need, when they need it.
First-in-human phase I clinical trial of NY-ESO-1 protein cancer vaccine with a novel adjuvant MIS416, NOD2 and TLR9 stimulant, for patients with NY-ESO-1 expressing solid tumors.
Authors: Mikiya Ishihara, Yasutaka Tono, Yoshihiro Miyahara, Naozumi Harada, Shinichi Kageyama, Takeshi Sasaki, Yasuhide Hori, Norihito Soga, Katsunori Uchida, Taizo Shiraishi, Eiichi Sato, Hideki Kanda, Toshiro Mizuno, Gill Webster, Hiroaki Ikeda, Naoyuki Katayama, Yoshiki Sugimura, Hiroshi Shiku
Journal: Journal of Clinical Oncology (2018)

e15176 Background: Complexes of Cholesteryl pullulan and NY-ESO-1 antigen (CHP-NY-ESO-1) present multiple epitope peptides to both the MHC class I and class II pathways. MIS416 is a non-toxic microparticle adjuvant that activates immune responses via NOD-2 and TLR9 pathways. Vaccination studies in mice have demonstrated that CHP-NY-ESO-1 with MIS416 enhanced anti-tumor efficacy. We conducted a First-in-Human clinical trial using CHP-NY-ESO-1 with adjuvant MIS416 for patients (pts) with NY-ESO-1-expressing refractory solid tumor (Clinical trial registration number, UMIN000005246, UMIN000008007). Methods: NY-ESO-1 expression was assessed by immunohistochemistry and/or RT-PCR. Pts received CHP-NY-ESO-1/MIS416 (C/M) 100/200, 200/200, 200/400 or 200/600 (μg/μg) (every 2 weeks, 6 doses total) followed by one vaccination every 4 weeks, until disease progression or unacceptable toxicity was observed. Response was assessed every 12 weeks by CT. The primary endpoints were safety and tolerability, and the secondary endpoint was immune response. Results: A total of 26 pts were enrolled. Median age was 70 years (range: 36-84). Median number of vaccination was 6 (range: 1-66). Seven pts (38%) received ≥7 doses. Enrollment to C/M 200/600 was stopped because of high frequency of SAE (2/4 pts) and little antitumor effect. Eight pts (31%) had SD or non-CR, non-PD. One pt (C/M 200/200) had no progression for 5 years at the end of study. Grade 1-2 injection site reaction was observed in all pts. Grade 3 drug-related AEs were observed in 6 pts (23%), hypertension (n = 5) and anorexia (n = 1). No grade 4-5 drug-related AEs were observed. Anti-NY-ESO-1 IgG1 response was attenuated significantly as the dose of MIS416 increased. Conclusions: C/M 200/200 and 200/400 were well tolerated. Further investigation is warranted. Clinical trial information: 000005246, 000008007.
P01.087 Reduced language lateralization in patients with a left-hemispheric glioma
Authors: G Kaya, J M Jansma, G J M Rutten
Journal: Neuro-Oncology (2018)

Functional magnetic resonance imaging (fMRI) is a powerful, non-invasive technique to examine brain functions. In clinical settings it can be used to localize language and motor functions preoperatively. One of the advantages of fMRI is that it can be used to study the overall functional organization of a tumor invaded brain. To this date, it remains unclear in what way tumors lead to changes in language activation patterns. More knowledge on these tumor related pattern changes (i.e. reorganization) can further improve preoperative risk assessment and clinical decision making, and consequently improve treatment. The aim of this study was to investigate the effect of the hemispheric location of a tumor on language lateralization in patients with gliomas. The hypothesis was that patients with left-hemispheric gliomas (‘LT’) show reduced language lateralization, as compared to patients with right-hemispheric gliomas (‘RT’) and healthy controls (‘HC’), respectively. This study used presurgical fMRI data of patients with LT (N= 39, male = 61%; age: 43.5 [±11.7]) and RT (N = 27; male: 74%; age: 48.5 [±13.7]), as well as HCs (N = 16; M: 37%; age: 27.6 [±5.4]). FMRI scans were produced using a 3T Philips scanner (PRESTO pulse sequence, voxel-size: 4x4x4 mm, TE: 1.5 sec), and were corrected for movement. The b-maps were spatially normalized to MNI space using SPM software. The average signal change during a covert verb generation task was calculated using six cube-shaped ROIs (15mm3) over Broca’s area (MNI coordinates: -54, 15, 0), Wernicke’s area (MNI: -54, -45, 0), dorsolateral prefrontal cortex (MNI: -54, 15, 30), and their right-hemispheric homologous. Language lateralization was calculated by subtracting the average signal change in the right-hemispheric ROIs from the average signal change in the left-hemispheric ROIs. A one-way analysis of variance (ANOVA) was conducted to examine group differences in lateralization. Post-hoc pairwise t-tests were performed for further investigation of the effect. The omnibus test revealed a significant difference in language lateralization between the three groups, F(2, 79) = 5.90, p = .004. Lateralization decreased from the HC (M = 0.28, SD = 0.16) to the RT (M = 0.25, SD = 0.16) and the LT (M = 0.14, SD = 0.17) group, in that order. Post-hoc t-tests showed that the difference in lateralization between LT and the RT group was statistically significant, t(64) = -2.65, p = .010. So was the reduction in lateralization in the LT group as compared to HCs, t(53) = -2.94, p =. 005. Patients with a glioma in the left hemisphere show reduced language lateralization, likely because the glioma interferes with the language network in the left hemisphere. Our results further suggest the possibility that the right hemisphere tries to compensate for this interference, showing stronger activation.
NOTCH1 Represses MCL-1 Levels in GSI-resistant T-ALL, Making them Susceptible to ABT-263
Authors: Anahita Dastur, AHyun Choi, Carlotta Costa, Xunqin Yin, August Williams, Joseph McClanaghan, Max Greenberg, Justine Roderick, Neha U. Patel, Jessica Boisvert, Ultan McDermott, Mathew J. Garnett, Jorge Almenara, Steven Grant, Kathryn Rizzo, Jeffrey A. Engelman, Michelle Kelliher, Anthony C. Faber, Cyril H. Benes
Journal: Clinical Cancer Research (2018)

Effective targeted therapies are lacking for refractory and relapsed T-cell acute lymphoblastic leukemia (T-ALL). Suppression of the NOTCH pathway using gamma-secretase inhibitors (GSI) is toxic and clinically not effective. The goal of this study was to identify alternative therapeutic strategies for T-ALL.We performed a comprehensive analysis of our high-throughput drug screen across hundreds of human cell lines including 15 T-ALL models. We validated and further studied the top hit, navitoclax (ABT-263). We used multiple human T-ALL cell lines as well as primary patient samples, and performed both in vitro experiments and in vivo studies on patient-derived xenograft models.We found that T-ALL are hypersensitive to navitoclax, an inhibitor of BCL2 family of antiapoptotic proteins. Importantly, GSI-resistant T-ALL are also susceptible to navitoclax. Sensitivity to navitoclax is due to low levels of MCL-1 in T-ALL. We identify an unsuspected regulation of mTORC1 by the NOTCH pathway, resulting in increased MCL-1 upon GSI treatment. Finally, we show that pharmacologic inhibition of mTORC1 lowers MCL-1 levels and further sensitizes cells to navitoclax in vitro and leads to tumor regressions in vivo.Our results support the development of navitoclax, as single agent and in combination with mTOR inhibitors, as a new therapeutic strategy for T-ALL, including in the setting of GSI resistance.
A randomized phase II trial of maintenance oral metronomic vinorelbine versus close observation in advanced non-small cell lung cancer (NSCLC) following platinum-based chemotherapy: MA.NI.LA. trial.
Authors: Marco Platania, Federico Nichetti, Luca Porcu, Felice Pasini, Mattia Boeri, Yasmina Modena, Alessandro Del Conte, Antonia Martinetti, Elisa Sottotetti, Daniele Pozzessere, Emanuela Vattemi, Francesco Verderame, Luigi Cavanna, Anna Paola Fraccon, Barbara Formisano, Rosaria Gallucci, Giuseppe Lo Russo, Valter Torri, Filippo G. De Braud
Journal: Journal of Clinical Oncology (2018)

e21101 Background: Several studies have proven the efficacy of maintenance chemotherapy (CT) in advanced NSCLC. The use of low dose (i.e. metronomic) anti-mitotic drugs could exert an anti-angiogenic effect while maintaining cytotoxic activity. This study aimed to assess the activity of metronomic oral vinorelbine as switch maintenance treatment following platinum-based CT in patients (pts) with advanced NSCLC Methods: In this multicenter, open label, randomized, controlled, phase II study (NCT02176369), pts with stage IIIb/IV NSCLC not progressing after 4 to 6 cycles of platinum-based CT received maintenance metronomic oral vinorelbine (50 mg three times weekly, ARM A) or close observation (ARM B). Randomization with a 1:1 allocation ratio was stratified for performance status (0-1 vs 2), histology (adeno vs other) and number of CT cycles (4 vs 6). The primary endpoint was progression free survival (PFS); an Hazard Ratio (HR) of 0.60 had to be detected (one-sided alpha: 0.05; power: 0.80). Secondary endpoints were overall survival, safety and QoL. Exploratory analysis investigated serum angiogenesis biomarkers (VEGFA, THBS1) and previous validated miRNA signature classifier (MSC) as predictors Results: A total of 120 pts were enrolled from January 2013 to April 2017. Median age was 68.7; M/F: 80/40; stage IIIb/IV:19/101; adeno/other:73/47; PS 0-1/2:113/7. After median follow up of 23.9 months, median PFS was 4.3 months for ARM A and 2.9 months for ARM B [HR = 0.76; 90%CI 0.56-1.05; one-sided p = 0.080]. The most common grade 3-4 adverse events in ARM A were neutropenia (27%), asthenia (6%) and anemia (4%). A total of 14 patients (28%) stopped vinorelbine for unacceptable toxicity. High VEGFA and THBS1 plasma levels and positive MSC expression were associated with shorter PFS (HR for 1000 unit, VEGF: 1.58; HR for 10000 unit, THBS1: 1.17; HR for MSC pos vs neg: 1.49) Conclusions: In advanced NSCLC following platinum-based induction CT, metronomic oral vinorelbine showed a modest, non-significant improvement in PFS. The safety analysis suggested the need for dose adjustment in case of further exploration of this strategy Clinical trial information: NCT02176369.
RNAi-mediated beta-catenin knockdown in the gastrointestinal mucosa (GI) of patients with familial adenomatous polyposis (FAP): Results of START-FAP trial.
Authors: Larn Hwang, Seymour H. Fein, Kevin Ng, Osmond D'Cruz, Sanjive Qazi, Wen Wang, David Nam, Annie Fong
Journal: Journal of Clinical Oncology (2017)

e15065 Background: FAP is an inherited GI disorder that predisposes patients to early-onset of colorectal cancer due to mutations in the APC gene resulting in accumulation of β-catenin contributing to the formation of polyps. CEQ508 is a novel agent using live-attenuated bacteria genetically engineered to produce and deliver β-catenin short-hairpin RNA into the GI mucosa. Methods: A dose-escalating Phase I study (START-FAP) evaluated the safety and tolerability of single daily oral doses of CEQ508 in FAP patients (3 each in Cohort 1 and 2 with 10 8 and 10 9 CFU for 28 days). The primary objective was to establish safety of oral CEQ508. The secondary objective was to test the effectiveness of CEQ508 in targeting β‐catenin gene in GI mucosa. GI tissues (duodenum, ileum, colon, antrum) obtained during endoscopy exam at baseline and end-of-treatment (EOT) were measured using qPCR and analyzed with ViiA™ 7 Real-Time system. Ct values were normalized to 2 of 3 housekeeping genes (EIF2B1, HPRT1, GUSβ). A mixed Nested-ANOVA model was used to evaluate β-catenin knockdown in normal mucosa and polyps. Results: Oral dosing of 10 8 and 10 9 CFU of CEQ508 for 28 days was well-tolerated. Histological evaluation of polyps and normal mucosa at baseline and EOT indicated minimal changes in tissue morphology or inflammation. β-catenin knockdown differed significantly between tissue types, with duodenum exhibiting the highest and antrum with the lowest (~2-fold difference). No significant effects from CEQ508 treatment were observed in normal mucosa. Significant reduction was observed in overall β-catenin expression in polyps at EOT (P = 0.0005). Patient to patient variation accounted for 8.2% of total variations. Reduction was observed primarily in the duodenum (39.3% decrease, P &lt; 0.0001) and ileum (28.8% decrease, P = 0.012). Conclusions: Bacterial delivery of RNAi via CEQ508 in FAP patients demonstrated an acceptable safety profile at the two bacterial dose levels tested, with no MTD having been identified. START-FAP achieved both the primary endpoint of safety and secondary endpoint of β-catenin knockdown. Clinical development of CEQ508 with Celecoxib/Lisinopril (IT-102) for FAP is planned.
Treatment (tx) journeys in newly diagnosed multiple myeloma (NDMM) patients (pts): Results from the Connect MM Registry.
Authors: Sundar Jagannath, Robert M. Rifkin, Cristina Gasparetto, Kathleen Toomey, Brian G. Durie, James W. Hardin, Howard R. Terebelo, Lynne I. Wagner, Mohit Narang, Sikander Ailawadhi, Shankar Srinivasan, Ahmed YoussefAgha, Brian Ung, Amani Kitali, E. Dawn Flick, Amit Agarwal, Rafat Abonour
Journal: Journal of Clinical Oncology (2018)

8041 Background: Real-world longitudinal data on tx sequencing & outcomes are limited. The Connect MM Registry is a US, multicenter, prospective observational cohort study designed to examine diagnostic & tx patterns, clinical outcomes & QoL in pts with NDMM. Using visual tools (Sankey Plots), tx sequences & transitions were longitudinally assessed in pts with NDMM from Connect MM who did or did not receive stem cell transplant (SCT, NSCT). Methods: Adult pts were enrolled ≤ 60 days from diagnosis in Cohorts 1 (n = 1493; 2009-2011) & 2 (n = 1518; 2012-2016). Tx were classified as containing: 1) immunomodulatory agents, 2) proteasome inhibitors (PI), 3) IMiD® agent + PI, 4) non-IMiD/PI agents (other), 5) tx gaps. Data is presented within Sankey plots, a type of flow diagram in which the proportional flow between variables (or nodes) is visualized. Flows between tx from first to last lines of tx, discontinuation, or death, were visually depicted & median progression-free survival (PFS) for lines 1, 2 & 3 of tx were examined. Results: As of Feb 2017, 966 SCT & 1941 NSCT pts have been treated (Table). Points of tx transitions were represented by nodes on the plots corresponding to a change in regimen, such as maintenance (or not), line 2 tx, line 3 tx, discontinuation or death. Substantial heterogeneity of treatment was observed. The most frequent treatment flow among SCT pts was IMiD agent + PI → IMiD agent → Ongoing (O) → Line Not Yet Reached (LNR) (16%); & for NSCT pts was PI → PI → O → LNR (8%). Outcomes per line of therapy were assessed. Median 1st PFS was nearly twice as long in all SCT pts compared to all NSCT pts. In SCT pts, median 1st, 2nd, & 3rd PFS measured from line start were 44.0, 8.3, & 4.5 mo; in NSCT pts, median 1st, 2nd, & 3rd PFS were 21.5, 7.3, & 5.8 mo, respectively. Conclusions: These real-world registry data depict the therapeutic journeys of pts with MM. The PFS by line data are similar to clinical trials of pts with MM. Clinical trial information: NCT01081028. SCT (n = 966) NSCT (n = 1941) Median follow-up, mo 31.8 37.5 Firstline (1L), n (%) PI 417 (43) 946 (49) IMiD agent 88 (9) 367 (19) IMiD agent + PI 450 (47) 525 (27) Other 11 (1) 103 (5) MT after 1L, n (%) Yes 620 (64) 511 (26) No 290 (30) 393 (20) Remain on initial tx 55 (6) 1037 (53)
Public awareness of breast cancer in Gaza: A cross-sectional study.
Authors: MohamedRaed Elshami, Hanan Abu Kmail, Maymona Abu-Jazar, Ibtisam Mahfouz, Dina Ashour, Ansam Aljamal, Nada Mohareb, Reem Dabbour, Jomana Ghaith, Tayseer Hasan, Reem Elbalaawi, Meral Abdelati, Esraa Saleh, Haifa Shawwa, Reem Al-Ghazali, Ola Obaid, Loai Albarqouni, Bettina Bottcher
Journal: Journal of Clinical Oncology (2018)

e22054 Background: Timely detection of breast cancer (BC) is important to reduce its related deaths. Hence, high awareness of its symptoms and risk factors is required. This study aimed to assess the awareness level of BC among females in Gaza. Methods: This is a cross-sectional study performed in September and October 2017 in Gaza, Palestine. Stratified sampling was used to recruit 4 hospitals and 7 high schools. A previously piloted, Arabic version of the Breast Cancer Awareness Measure (BCAM) questionnaire was used. BCAM is a validated standardized questionnaire to measure public BC awareness, which consists of 6 sections: sociodemographic data, confidence and behavior in relation to breast changes, awareness of BC symptoms, awareness of BC risk factors, barriers to seek medical help, and knowledge of BC screening. Women (aged ≥18 years) visiting or admitted to any of the 4 hospitals, and female adolescents (aged 15-17 years) in any of the 7 schools were recruited for face-to-face interviews to complete the BCAM. Patients and visitors to oncology departments were ineligible. Informed consent and ethical approval were obtained. Data were analyzed with SPSS (version 23). Results: Of 3055 approached, 2774 participants completed the BCAM questionnaire (response rate = 90.8%). 1588 (57.2%) were adults and 1186 (42.8%) were adolescents. 1781 (64.2%) reported that they rarely (or never) check their breasts, and 909 (32.8%) were not confident to notice changes. 1675 (60.4%) were aware about the availability of BC screening program. A breast lump was the most commonly recognized symptom (n = 2166, 78.1%) while pulling in of nipple was the least (n = 1009, 36.4%). Having a past history of BC was the most frequently reported BC risk factor (n = 1333, 48.1%) and having an early menarche was the least (n = 430, 15.5%). The overall mean score for awareness of BC symptoms was 24.9 ± 5.5 out of 33 and that of risk factors 22.9 ± 4.2 out of 45. Feeling scared was the most reported barrier to seek medical advice among women (n = 802, 50.2%) whereas feeling embarrassed was most commonly reported in adolescents (n = 745, 62.8%). Conclusions: Awareness of BC symptoms, risk factors and screening programs is suboptimal in Gaza. Educational interventions to raise public awareness of BC are warranted.