tbuckley/cabot-search huggingface dataset:
Survival impact of secondary cytoreductive surgery for platinum-sensitive relapsed serous ovarian cancer.
Authors: Jingjing Liu, Xiaoyun Wan, Yuanming Shen, Xueqian Qian
Journal: Journal of Clinical Oncology (2018)

e17546 Background: The aim of this study was to evaluate effectiveness of secondary cytoreductive surgery in platinum-sensitive relapsed serous ovarian cancer (RESOC) patients and to assess prognostic factors on overall post-recurrence survival time. Methods: From the electronic databases of the Department of gynecological oncology at Women's Hospital School of Medicine Zhejiang University between 2000 and 2015, a cohort of 190 RESOC patients were selected using the following inclusion criteria: primary ovarian、peritoneal and fallopian tubal cancer with serous histology who had received up to three previous courses of platinum-based chemotherapy and who were progression free for at least 6 months.These patients were divided into two groups according to the therapy method after relapse: secondary cytoreduction & chemotherapy (n = 28) and chemotherapy alone (n = 162). Survival analysis and comparisons were performed using the Kaplan-Meier method, Log-rank test, Wilcoxon test and Cox multivariate proportional hazards model Results: The overall survival (OS) in secondary cytoreduction & chemotherapy group was significantly longer than the chemotherapy alone group, the median OS was 75 months (95%CI 56.261-93.739) versus 45 months (95%CI 40.518-49.482) (p < 0.001). Univariate analysis showed that the median OS was significantly correlated with primary optimal cytoreduction(p = 0.003), early stage(p = 0.021), CA125≤1000U/ml (p = 0.009), recurrent interval > 12months (p < 0.001) and secondary cytoreduction (p < 0.001). Multivariate Cox regression analysis revealed that primary optimal cytoreduction, recurrent interval and therapy method after relapse were independent associated factors (P = 0.008, P < 0.001, p = 0.002 respectively). Conclusions: After careful selection, optimal cytoreduction can be achieved in most patients who are subjected to secondary surgical cytoreduction with a better OS. Primary optimal cytoreduction and recurrent interval represent the most important prognostic factors.
Network metanalysis and cost-effectiveness of abiraterone, docetaxel or placebo plus androgen deprivation therapy (ADT) for hormone-sensitive advanced prostate cancer.
Authors: Pedro Nazareth Aguiar, Pui San Tan, Sarah Simko, CARMELIA MARIA NOIA BARRETO, Barbara Gutierres Aguiar, Auro Del Giglio, Gilberto Lopes
Journal: Journal of Clinical Oncology (2018)

6615 Background: Prostate cancer is the leading neoplasm among men worldwide. The objective of this study is to evaluate the cost-effectiveness of the addition of chemotherapy or abiraterone to ADT after a network meta-analysis and an indirect comparison between chemotherapy and abiraterone. Methods: We made a literature review and included studies that evaluated the addition of docetaxel or abiraterone to ADT versus ADT alone for patients with castration-sensitive metastatic prostate cancer. Studies’ outcomes were modeled on a logarithmic scale using the Bayesian hierarchical model for indirect comparisons between interventions. Then, we developed an analytical model to determine the cost-effectiveness of the addition of docetaxel or abiraterone versus ADT alone. Direct and indirect costs were included in the model considering Brazilian costs. Results: Four clinical trials were included in the network meta-analysis. Evidence suggests that the addition of abiraterone to ADT is the best therapeutic option in terms of OS ( > 95% probability; HR 0,81; 95% CrI 0,66 – 1,00) and FFS ( > 99% probability; HR 0,50; 95% CrI 0,40 – 0,62) compared to ADT plus docetaxel. Abiraterone plus ADT had fewer cases of febrile neutropenia than docetaxel plus ADT (1% versus 15%). Compared to ADT alone, the addition of chemotherapy generated 0.492 QALY and the addition of abiraterone generated 0.999 QALY. Abiraterone led to a QALY gain of 0.506 compared to docetaxel. In Brazil, the incremental costs per QALY were $40,500, $100,251 and $173,145, respectively. At current costs, docetaxel plus ADT is more cost-effective than abiraterone plus ADT. The factors that had the greatest influence on cost-effectiveness were the overall survival and failure-free survival confidence intervals. Price discounts on abiraterone purchasing was the factor that led to the greatest impact on the incremental cost (ranging from $100,000 to $40,000). Conclusions: We conclude that the addition of chemotherapy to ADT is more cost-effective than the addition of abiraterone to ADT. However, discounts on abiraterone cost might improve cost-effectiveness.
Rhinitis in children and adolescents with asthma: Ubiquitous, difficult to control, and associated with asthma outcomes
Authors: Alkis Togias, Peter J. Gergen, Jack W. Hu, Denise C. Babineau, Robert A. Wood, Robyn T. Cohen, Melanie M. Makhija, Gurjit K. Khurana Hershey, Carolyn M. Kercsmar, Rebecca S. Gruchalla, Andrew H. Liu, Emily Wang, Haejin Kim, Carin I. Lamm, Leonard B. Bacharier, Dinesh Pillai, Steve M. Sigelman, James E. Gern, William W. Busse
Journal: Journal of Allergy and Clinical Immunology (2018)
SATB2 loss and the immune milieu of colorectal cancer (CRC).
Authors: Darran O'Connor, Donal J. Brennan, Kirsha Naicker, Sudipto Das, Bruce Moran, Rut Klinger, Fredrik Ponten, Stephen M. Hewitt, Karin Jirstrom, Annette T. Byrne, Jacintha O'Sullivan, William M. Gallagher
Journal: Journal of Clinical Oncology (2018)

3569 Background: SATB2 orchestrates gene expression by regulating higher-order chromatin structure. Antibody screening of 48 normal human tissues and 20 cancers, showed SATB2 as almost exclusively expressed in gastrointestinal tissue. We confirmed this in 10,533 further samples. Methods: Tissue microarray (TMA) analysis was used to determine SATB2 expression in CRC, Kaplan-Meier analysis and the log rank test were used to illustrate differences between disease-specific survival (DSS) according to SATB2 expression. Cox regression proportional hazards models were used to estimate the relationship between outcome and SATB2 expression, grade, age, stage, differentiation and gender. Gene set enrichment analysis (GSEA) was used to identified pathways associated with loss of SATB2 expression and RNAi was used to modulate SATB2 in cell lines. Results: Differential SATB2 expression was observed in CRC, with loss occurring along the adenoma-carcinoma sequence (n = 320, p = 0.023). SATB2 expression was decreased in metastatic SW620 cells and knockdown of SATB2 in SW480 cells increased their growth and migratory capacity. By automated image analysis of SATB2 expression in CRC (n = 309), SATB2 was found to be an independent predictor of DSS (HR = 0.52, 95% CI 0.32-0.83, p = 0.006). SATB2 was examined in a second cohort (n = 290) and again, found to be an independent predictor of DSS (HR = 0.40, 95% CI 0.18-0.92, p = 0.031). SATB2 significantly correlated with CD3+ infiltrates (p = 0.006) and inversely correlated with COX2 expression (p = 0.019). In two independent CRC cohorts (n = 467), SATB2-low tumours were found to be significantly enriched in the CMS1 (immune-related) subtype (p < 0.001). GSEA revealed that SATB2-low tumours demonstrated altered immune signalling with significant increases in IFNγ (p = 0.001), IL6 (p = 0.001), IL8 (p < 0.001) TFGβ (p < 0.001), which was mirrored by manipulation of SATB2 in CRC cells. Furthermore, in a longitudinal cohort of ulcerative colitis patients, we found a significant correlation between loss of SATB2 and occurrence of future cancers (p = 0.013). Conclusions: We postulate that SATB2 acts as a master regulator of inflammation in the gut and loss of expression is significantly associated with the progression of colorectal cancer.
P02.16 Evaluating the therapeutic potential of anti-CD19 chimeric antigen receptor T-cells in a murine model of human primary CNS lymphoma using long-term in vivo imaging
Authors: M Mulazzani, S Fräßle, S Langer, I von Mücke-Heim, V Buchholz, A Straube, D Busch, L von Baumgarten
Journal: Neuro-Oncology (2018)

Multi-agent chemotherapy has led to an improved survival in patients suffering from primary CNS lymphoma (PCNSL). Still, long-term disease remission is rare and therapy associated side effects are common. In recent years, a growing body of evidence has demonstrated the therapeutic potential of chimeric antigen receptor (CAR) T-cells in systemic B-cell malignancies. Studies on CAR T-cells targeting human CD19 (CD19CAR T-cells), a pan B-cell antigen also expressed by PCNSL cells, have produced promising clinical results. However, little is known about the interaction of CD19CAR T-cells and PCNSL cells in vivo. The aim of this study was to evaluate the proliferation, tumour infiltration and long-term persistence of CD19CAR T-cells as well as the therapeutic effect on PCNSL growth. We established a novel PCNSL model in T-cell deficient nude mice. After microsurgical implantation of a cranial window, red fluorescent, human B-cell lymphoma cells were injected stereotactically into the animal’s cortex. Once a tumour had grown to a diameter of 500 µm, the mice were allocated either to the treatment or to the control group. In the treatment group, green fluorescent CD19CAR T-cells were injected in close proximity to the PCNSL into the cortex. Animals of the control group were injected with mock CAR T-cells, which lacked the extracellular domain of the CAR. To visualise the interactions of CAR T-cells with lymphoma cells, multiple two photon microscopy sessions were conducted over several weeks. The in vivo interaction of CD19CAR T-cells and tumour cells led to proliferation of CD19CAR T-cells in the treatment group. Within a few days after injection, CD19CAR T-cells resided adjacent to the tumour and infiltrated tumorous tissue in large quantities. In the treatment group, significant tumour growth inhibition and disease regression was observed. In contrast, mock CAR T-cells barely proliferated and only marginally infiltrated the tumour or eliminated tumour cells. Long-term persistence of CD19CAR T-cells was detected in the brain, lymph nodes and blood, even after tumour regression. Our study illustrates the in vivo characteristics of CD19CAR T-cells, their anti-tumorous effect and long-term persistence. These results emphasize the therapeutic potential of CD19CAR T-cells in PCNSL. Based on these results, clinical studies to assess the efficacy and safety of CD19CAR T-cells in humans suffering from PCNSL are highly warranted.
Nivolumab (nivo) for patients (pts) with metastatic non-clear cell renal cell carcinoma (nccRCC): A single-institution experience.
Authors: Jad Chahoud, Matthew T. Campbell, Jianjun Gao, Amado J. Zurita, Amishi Yogesh Shah, Pavlos Msaouel, Jeremy Aaron Ross, Lianchun Xiao, Eric Jonasch, Padmanee Sharma, Nizar M. Tannir
Journal: Journal of Clinical Oncology (2018)

4585 Background: Nivo is approved for refractory metastatic renal cell carcinoma (RCC). However, the clinical activity of nivo in nccRCC is unknown as these patients were excluded from the trial population. Methods: We conducted a retrospective study of pts who received at least one dose of nivo for histologically-confirmed nccRCC. We tabulated treatment characteristics, objective response according to RECIST v1.1, adverse events (AEs), progression-free survival (PFS) and overall survival (OS). Results: Between 3/2010 and 12/2017, we identified 40 pts with nccRCC; 12 (30%) had papillary histology, 10 (25%) unclassified, 5 (12.5%) chromophobe, 3 (7.5%) translocation, 8 (20%) had ccRCC with rhabdoid component, 1 (2.5%) mucinous tubular and spindle cell carcinoma and 1 (2.5%) sarcomatoid RCC. Median age was 58 years (17-80) and 82.5% were male. The majority of pts had ECOG PS 1 (65%) or 2 (27.5%). At start of nivo therapy, 85% had metastatic disease in ≥ 2 sites; 7.5 % had International Metastatic RCC Database Consortium favorable-risk, 72.5% intermediate- and 20% poor-risk disease. Most pts (82.5%) had prior nephrectomy and median number of prior lines of therapy was 2 (0-8) with 60% of pts receiving ≥ 2 prior VEGFR-TKIs. The majority received nivo monotherapy (n = 32, 80%), and 20% (n = 8) received a combination of nivo with anti-VEGF or anti-CTLA4 therapy. At a median follow-up of 20 mo (16.2, 29.6), median PFS was 5.4 mo (3.4-10.2), with a 6-mo PFS rate of 45% (31.6%-64.2%). Median OS was 17.3 mo (7.8-NA), and 1-yr OS 60.1% (45.7%-79.1%). Disease control rate for 32 pts evaluable for best response was 78.1% (CR 6.25% + PR 9.37% + SD 62.5%), 12 pts (37.5%) had stable disease ≥ 6mo. Most common AEs were diarrhea (10%) and fatigue (17.5%). Nivo was stopped secondary to intolerance in 7 pts, 4 of whom achieved durable disease control. There were no treatment-related deaths. Conclusions: Nivo demonstrated clinical benefit and was well-tolerated in pts with nccRCC. Until there is evidence from prospective clinical trials, this retrospective data supports the use of nivo in pts with metastatic nccRCC.
Developing educational interventions and clinical tools to improve risk-based prevention and management of tumor lysis syndrome (TLS).
Authors: Mitchell S. Cairo
Journal: Journal of Clinical Oncology (2018)

e18811 Background: TLS is a potentially life-threatening consequence of cancer treatment resulting from massive tumor cell lysis (Cairo et al, BJH, 2004). The best way to manage this oncologic emergency is through prevention, however the risk for TLS is often underestimated. To address this gap, we launched a continuing medical education (CME) expert interview on the ReachMD medical broadcast network. Methods: In October 2017, a CME program consisting of a 30-minute expert interview (Dr. Mitchell Cairo) was launched across all platforms within the ReachMD network (ReachMD.com, ReachMD Radio Network, mobile apps/podcasts on iTunes). The program focused on a comprehensive TLS risk classification system developed by an international expert consensus (Cairo et al, BJH, 2010). A downloadable clinical tool, including a TLS risk stratification algorithm and prophylaxis/management recommendations accompanied the program. Pre-/post-activity tests and evaluations were assessed to measure any gains in knowledge/confidence and intended practice change. Results: 3 months post-launch, nearly 9,000 clinicians participated in this CME. Post-test results were analyzed from 196 learners who completed the activity, which demonstrated significant overall improvements in knowledge. The proportion of participants who answered questions correctly pre-education was 45% (± 30%) vs 63% (± 17%) post-education (P = 0.003). There was also a 50% significant increase in mean confidence rating (ranked from 1, no confidence to 5, complete confidence) in a clinician’s ability to identify patients at risk for TLS and apply appropriate prevention/treatment strategies. Mean confidence rating pre-education was 2.5 (± 1.4), which increased to 3.8 (± 1.0) post-education (P < 0.0001). The majority (90%) of participants also identified specific changes they intend to make in their practice, such as improving patient assessment and better identifying patients at risk for TLS. Conclusions: An educational expert interview offered across multiple e-learning formats significantly increased the knowledge and confidence of clinicians’ to incorporate risk-based management of TLS.
Long survival (SV) for metastatic renal cell cancer (mRCC) after cytoreductive nephrectomy (CN) plus lung metastasectomy (LM) without targeted therapy (TT).
Authors: Jose F. Corona-Cruz, Miguel Patricio Moscoso-Fernandez Salvador, Laura Alejandra Ramirez-Tirado, Josue Andres Gonzalez-Luna, Miguel A. Alvarez, Miguel Angel Jimenez-Rios, Raúl Alejandro López Saucedo, Edgardo Jimenez-Fuentes, Oscar Gerardo Arrieta Rodriguez
Journal: Journal of Clinical Oncology (2018)

e16564 Background: Reported 5-year SV for mRCC is about 10%. Introduction of inhibitors of VEGF and mTOR pathways have improved Progression Free Survival and Overall Survival (OS). High cost of new therapies is associated with limited access in Developing Countries. CN plus LM has been reported as an alternative of treatment in oligometastatic disease and is associated with prolonged SV for selected patients (pts). Methods: Retrospective, single center cohort of patients with mRCC and isolated lung metastases. Data were collected from a prospective database. Primary endpoints were OS and Disease Free Survival (DFS) analyzed using Kaplan-Meier method with log-rank test and Cox regression model. OS was calculated from date of LM to death of disease or last follow-up. DFS was calculated from date of LM to date of first recurrence. Secondary endpoints were morbidity and mortality of LM Results: From Jan 2005 to Dec 2015, 43 pts underwent CN plus LM, none received neoadjuvant or adjuvant systemic treatment for lung metastases. Mean age 56.3 years (36 – 84). At time of diagnosis of primary tumor, metastases were identified in 32.6% of pts. Single metastases were resected in 39.5% pts. Median number of resected metastases 4.8 (1 – 25). Complete resection (R0) rate 90.7%. Median follow-up 36.4 months (1 – 135). Median DFS 18.0 months (11.4 – 24.5). A relapse was documented in 20 ptes (46.5%); isolated lung relapse was present in 11ptes and a re-metastasectomy was attempted in 9 ptes. Only 6 ptes received TT at time of relapse. OS 54.6 months (26.0 – 83.2), 5-year OS 42%. Multivariate analysis showed incomplete resection as the only independent factor associated with OS, HR 2.03 (95% CI 1.03 – 4.02 p = 0.04) Secondary endpoint analysis showed that LM is a safe procedure, with 90-day morbidity and mortality of 2.3% and 0%, respectively Conclusions: Pts with mRCC limited to lung who undergo LM and CN show a prolonged OS despite of not receiving up-front TT. LM with CN can be considered as a safe and effective therapeutic approach in this ptes. This study suggests the possibility of offering CN plus LM as an initial treatment modality followed by close surveillance, thus saving TT for recurrent disease.
P01.089 The patients’ perspective on information level about supportive care in glioma patients - post-hoc evaluation and development of an online survey focusing on patients’ information needs, clinical studies and alternative therapies.
Authors: M Ottenhausen, C Richter, F Ringel, J Coburger, M Renovanz
Journal: Neuro-Oncology (2018)

The prognosis of malignant gliomas remains poor despite ongoing efforts to improve treatment protocols. Therefore patients search for further therapy information, especially in the outpatient setting. The aim is to assess 1) the information level of patients 2) the information needs of the patients regarding therapy and support and 3) to evaluate the patients’ opinion towards experimental trials and alternative therapies. First we performed a post-hoc analysis of the data of the ERASMUS study where we applied the Patients’ Perspective Questionnaire (PPQ) assessing psychosocial distress as well as support requested and received by patients for specific domains (e.g. family, doctor, mobile care etc.) and information needs of the patients (rated on a Likert scale with regarding the subjective information level reaching from 1–5, 1= inadequate informed to 5= optimal informed). After a thorough review of the literature and analyzing the PPQ results of the previous study, an anonymous online survey was designed and is ongoing. It has to be completed through a web-based platform and includes 10 topics focusing on how patients obtain information about therapy and support, the use of alternative therapies. In the ERASMUS study n=232 glioma patients were assessed at least once, n=129 (56%) were male, mean age was 52 years (range 20–87) and n=190 (84%) harbored a high-grade glioma (HGG). Subjective mean level of information about the disease and therapy was moderate (mean= 3.5, SD= 1.3). Beside of requested support by doctors and psychologists, patients longed for more information about social service (11%), mobile care (13%) and nutrition counselling (15%), especially patients with recurrent tumors (n= 57) longed more often for support by dieticians (n=17) than those with primary diagnosis (p= .009, 95%CI= 1.28 - 4.33, Fishers’ exact). 50% of patients responding to the survey were male and 50% harbored a glioblastoma and all respondents knew the molecular profile of the tumor. Respondents required information about ongoing trials, psychosocial support, sport and nutrition but also alternative therapies. Patients with HGG require information about the disease, the therapy but also topics regarding activity and nutrition. A comprehensive approach is required providing also information about paramedical topics. Our survey might provide further information for neuro-oncologists about patients’ needs in order to offer optimal patient guidance and care.
First results from the primary analysis population of the phase 2 study of erdafitinib (ERDA; JNJ-42756493) in patients (pts) with metastatic or unresectable urothelial carcinoma (mUC) and <i>FGFR</i> alterations (FGFRalt).
Authors: Arlene O. Siefker-Radtke, Andrea Necchi, Se Hoon Park, JesÃºs GarcÃa-Donas, Robert A Huddart, Earle Frederick Burgess, Mark T. Fleming, Arash Rezazadeh, Begona Mellado, Sergei Varlamov, Monika Joshi, Ignacio Duran, Scott T. Tagawa, Anne OHagan, Anjali Narayan Avadhani, Bob Zhong, Peter De Porre, Yohann Loriot
Journal: Journal of Clinical Oncology (2018)

4503 Background: ERDA is an FGFR inhibitor with activity in pts with mUC and FGFRalt. FGFRalt occur in 10-20% of mUC and are enriched in immunologically "cold" luminal 1 UC. Two independent published reports showed a 5% investigator-reported response rate to prior immune checkpoint inhibitors (ICI) among pts with select FGFRalt, suggesting a need for new treatment options in this population. Here we report efficacy and safety of ERDA in the global open-label phase 2 study BLC2001 (NCT02365597). Methods: Pts had measurable mUC with prespecified FGFRalt, ECOG 0-2, and progression during/following ≥ 1 line of prior chemo or ≤ 12 mos of [neo]adjuvant chemo, or were cisplatin ineligible, chemo naïve. Prior ICI treatment was allowed. The optimal schedule of ERDA determined in the initial part of the study was 8 mg/d continuous ERDA in 28-d cycles with uptitration to 9 mg/d if protocol-defined target serum phosphate level was not reached and if no significant treatment-related adverse events (TRAEs) occurred. Primary end point was ORR, with a null hypothesis of ORR ≤ 25%. Results: 96 pts were treated with median 5 cycles of optimized ERDA dose regimen; 10% were chemo naïve, 47% had received ≥ 2 prior lines of therapy, 80% had visceral metastases. There was a 42% confirmed (c) ORR (RECIST 1.1) (3% CR, 39% PR) and 80% disease control rate (CR + PR + SD). There was a 70% cORR among pts with prior ICI (n = 21). AEs were manageable; 10% discontinued due to TRAEs; there were no treatment-related deaths (Table). Conclusions: Treatment with ERDA yielded a robust response rate and was tolerable in pts with chemorefractory mUC and FGFRalt, a population with poor prognosis and high unmet need based on low response rate to prior ICI. Final primary analysis results, including OS, PFS, and response duration, will be presented. Phase 3 is ongoing. Clinical trial information: NCT02365597. ERDA (n = 96) AEs, n (%) Serious TRAEs 7 (7) All Grade 3* Most common TRAEs, any grade Hyperphosphatemia 66 (69) 2 (2) Stomatitis 45 (47) 8 (8) Diarrhea 40 (42) 3 (3) FGFR inhibitor class effect AEs (summed terms) Skin and nail AEs 63 (66) 13 (14) Eye AEs 55 (57) 5 (5) Retinopathy 2 (2) 1 (1) *Highest grade of listed TRAEs.