tbuckley/cabot-search huggingface dataset:
A phase IB trial of 5-azacitidine (5AC) and suberoylanilide hydroxamic acid (SAHA) in patients with metastatic or locally recurrent nasopharyngeal carcinoma (NPC) and NK-T cell lymphoma.
Authors: Wen Son Hsieh, Eng Huat Tan, Wan-Teck Lim, Ross A. Soo, Anthony T. C. Chan, Edwin P. Hui, Soo-Chin Lee, John Soon Wah Low, Pei Li Lim, Thomas Kwok Seng Loh, Matthew M. Ames, Joel M. Reid, Paul Gerard Murray, Qian Tao, Boon C. Goh, Richard F. Ambinder
Journal: Journal of Clinical Oncology (2013)

e17017 Background: Epigenetic up-regulation of EBV and cellular genes via demethylation and histone deacetylase inhibition can induce EBV lytic replication enhancing immune mediated tumor killing and up-regulation of tumor suppressor genes resulting in tumor apoptosis. Methods: Patients (Pt) with relapsed or refractory NPC and NK-T cell lymphomas were enrolled to determine safety, tolerability, pharmacokinetics (PK), pharmacodynamics and preliminary anti-tumor activity using a dose escalation design. 5AC was administered on days 1 to 10 sub-cutaneously while SAHA was administered on days 1 to 14 orally. PK for SAHA, EBV viral load, characterization of circulating EBV, Immunohistochemistry (IHC) and EBV promoter methylation analysis in tumor tissue were performed. Results: 11 pt have been treated (M:F 8:3, median age 48, R: 35-71) at 3 dose levels – 5AC 50 mg/m 2 and SAHA 200 mg b.i.d. (dose level 1), 5AC 37.5 mg/m 2 and SAHA 200 mg q. am and 100 mg q. pm (dose level 2), and 5AC 25 mg/m 2 and SAHA 100 mg b.i.d (dose level 3). Median number of previous treatment regimens was 3 (R:1-6). Dose limiting toxicities (DLT) were seen in 2/2 pts at dose level 1: grade 4 thrombocytopenia (1 pt), grade 3 nausea, vomiting and fatigue (2 pts), and grade 5 hepatic failure (1 pt). Two of six patients at dose level 2 experienced DLT: grade 3 fatigue (1 pt) and worsening of pre-existing Sweet’s Syndrome (1 pt). Common AEs (G1/2) included fatigue (73%), cough (64%), anorexia (55%), and injection site reaction (45%). One minor response was seen and 5 pt had prolonged stable disease (&gt;16 weeks), including one patient for 88 weeks. Analysis of post-treatment tumor biopsies showed demethylation of EBV lytic cycle gene promoters after treatment. SAHA PK, IHC results for EBV gene expression in tumor tissue, EBV viral load and characterization of circulating EBV will be presented. Conclusions: 5AC/SAHA appears to be tolerable at dose level 3 with suggestion of clinical benefit. Analysis of post-treatment tumor and blood samples suggests that modulation of EBV gene expression may play a role in the mechanism underlying clinical benefit. Continued accrual at dose level 3 is ongoing. Clinical trial information: NCT00336063.
Project Data Sphere initiative: Results from first 6 months of broad access to oncology trials data.
Authors: Kald Abdallah, Robin Jenkins, Charles Hugh-Jones, Joel Beetsch, Gregory A. Curt, Mace L. Rothenberg, Fang Liz Zhou, Ronit Simantov, John Dornan, Martin J. Murphy
Journal: Journal of Clinical Oncology (2015)

e17691 Background: Analysis of Phase 3 data from any clinical trial is uncommon beyond the pre-defined protocol. Aggregation of data from multiple trials make new analyses possible. Project Data Sphere, LLC (PDS) was established as an independent initiative of the non-profit CEO Roundtable on Cancer to carry out its Life Sciences Consortium’s initiative to provide a single platform to share, integrate, and analyze historical comparator-arm cancer trial data sets from Phase 3 trials. Methods: : Launched in April 2014, the PDS website (www.ProjectDataSphere.org) was developed by the SAS Institute and provides authorized users free access to data analytical software and patient-level raw data, which the providers de-identified, from control arms of Phase 3 trials from any source. The simple user application process is free. Results: At launch, there were 4,000 patient records derived from 9 data sets contributed by 7 industry and academic data providers. As of January 2015, the number of data sets increased to 18, with over 10,000 patient records encompassing prostate, pancreatic, breast, colorectal, lung, and other cancers. The number of authorized users increased from 83 at launch to 285 (January 2015). Data sets were downloaded over 1,100 times by a user community made up of data managers/programmers (25%), biostatisticians (15%), oncologists (11%), and basic scientists (10%), and others. Data users are from academia (37%), industry (33%), non-profit organizations (6%), government (2%), and other organizations. Most users are from North America (79%), the remaining are from 19 countries. As of January 2015, at least 5 publications are being prepared for peer-reviewed publication. Conclusions: PDS provides a smoothly functioning, readily accessible unique model to share and integrate clinical trial data from multiple sources. The rapid growth of users, downloads, and publications demonstrates a viable approach to accelerating research through aggregation of patient-level data that may lead to important new insights and discoveries. PDS also provides a vehicle to explore innovative ways to analyze data (e.g. crowdsourced computational challenges) without exposing patients to new clinical trials.
Is there an additional benefit of Tc-99m-PSMA-guided gamma probe use for salvage lymph node dissection in recurrent prostate cancer.
Authors: David Pfister, Matthias Schmidt, Friederike Haidl, Daniel Porres-Knoblauch, Alexander Drzezga, Axel Heidenreich
Journal: Journal of Clinical Oncology (2017)

e591 Background: PSMA-PET/CT is the most sensitive diagnostic tool in biochemical recurrent prostate cancer to detect minimal metastatic disease. However, it may be difficult to localize small PSMA-positive lymph nodes intraoperatively. Therefore, it was the aim to investigate whether preoperative Tc-99m-PSMA targeting may improve intraoperative tumor localization by use of a gamma probe. Methods: In 13 Patients Ga-68-PSMA-PET/CT identified iliac lymph nodes in patients suitable for salvage lymph node dissection. On the day before operation a mean activity of 480 MBq Tc-99m-PSMA was injected and gamma camera scintigraphy + SPECT was performed 4-5 hours after tracer application. About 24 hours after tracer application a salvage lymph node dissection was performed on the side of initial suspicious lymph node metastases. Sensitivity, specifity, pos and neg. predictive values were calulated for PSMA-PET/CT and gamma probe use to analyse the additional use. Results: In 9 / 13 patients PSMA-positive metastatic lymph nodes were identified in Ga-68 PSMA-PET/CT. A total of 156 lymph nodes were removed with 14 lymph nodes in 9 patients being positive in histopathologic examination. Sensitivity, specifity, pos and neg. predictive values for PSMA PET/CT and gamma probe were 85% and 79%, 99% and 100%, 85% and 100% and 99% and 98% respectively. In one patient only gamma probe use identified a pathologic lymph node. Conclusions: Gamma probe guided salvage lymph node dissection in PSA recurrent prostate cancer is feasible and had a high concordance with PSMA-PET/CT. However, the additional diagnostic benefit is limited compared to PSMA-PET/CT because in only one patient (7%) a positive lymph node could be identified with the use of the gamma probe outside the standard operative area in salvage lymph node dissection.
Does age impact treatment of head and neck squamous cell carcinomas? A retrospective monocentric study about 107 patients age 75 and over.
Authors: Laurence Digue, Aurelie Ducournau, Cecile Mertens, Claire Majoufre-Lefebvre, Marie-Quitterie Picat, Sigolene Galland-Girodet, Erwan De-Mones-Del-Pujol
Journal: Journal of Clinical Oncology (2014)

6065 Background: About 30% of head and neck carcinomas occur in patients over 70, and 10% in patients over 80. There is no standard of care for this population, which is under-represented in clinical trials. How are non-metastatic patients 75 and over treated in routine practice? Methods: Our study is a retrospective analysis based on 107 patients aged 75 and over (median 81.4 [75-94]) with non-metastatic squamous cell head and neck carcinomas treated in Bordeaux Academic Hospital between March 2007 and March 2012. We compared, for each patient, the standard treatment proposed to younger patients as described by international recommendations (NCCN, ESMO), the treatment recommended in multidisciplinary staff, and the treatment ultimately received. Results: Of the 107 patients, 69 (64.5%) were males and 38 (35.5%) females. 51.4% had an oral cavity cancer, 16.8% oropharyngeal, 15.9% laryngeal, 13.1% hypopharyngeal and 2.8% prevalent cervical lymph node without primary tumor. The standard treatment was proposed by multidisciplinary staff in less than 40% of patients, because of their deteriorating performance status (PS), chronological age and/or comorbidities. The treatment recommendedby multidisciplinary staff (with patients present in ¾ of the cases) was ultimately received in more than 80% of cases. In the others, the proposed treatment was not administered because of patient’s deteriorating PS or their refusal. Only 15 patients had a geriatric assessment and none of them received the standard treatment. Treatment toxicities were acceptable and similar to those found in literature for younger patients. At 5 years, overall survival of our population was 14.5%, but specific survival was 74,5%. Our population passed away more from comorbidities than from their cancer after the first 2 annual follow-ups. Conclusions: We recommend the systematic completion, before treatment proposal, of at least one easy screening of geriatric fragilities in order not to under or over-treat these patients, and a prompt start of treatment after decision by multidisciplinary staff because of quick deterioration of PS. We also recommend that elderly patients can be included in clinical trials.
Do quality of life and physical function at diagnosis predict short-term outcomes during intensive chemotherapy in acute myeloid leukemia patients?
Authors: Narhari Timilshina, Henriette Breunis, Joseph Brandwein, Mark D. Minden, Vikas Gupta, Madeline Li, George A. Tomlinson, Rena Buckstein, Shabbir M.H. Alibhai
Journal: Journal of Clinical Oncology (2013)

7067 Background: Intensive chemotherapy (IC) used to treat acute myeloid leukemia (AML) is associated with multiple short-term toxicities including mortality, particularly in older adults. Emerging data suggest that baseline quality of life (QOL) assessment and/or objective physical function tests may predict outcomes in oncology, although there are no data in AML patients. We investigated the association between baseline QOL and physical function with short-term treatment outcomes in adult and elderly AML patients. Methods: We conducted a prospective, longitudinal study of adult (age 18+) AML patients undergoing IC. Prior to starting IC, patients completed the EORTC QLQ-C30 and FACT-Fatigue in addition to physical function tests (grip strength, timed chair stands, and 2-minute walk test). Outcomes included 60-day mortality, intensive care unit (ICU) admission, and achievement of complete remission (CR). Univariate and multivariable logistic regression were performed to evaluate each outcome. Results: Of the 243 patients (median age 57.5 y), 56.7% were male and median Charlson comorbidity score was 0. 60-day mortality, ICU admission, and CR occurred in 9 (3.4%), 15 (6.2%), and 171 (70.4%), respectively. In univariate regressions, neither QOL nor physical function tests were predictive of 60-day mortality (all P&gt;0.05), whereas cytogenetic risk group (P=0.04), ICU admission (P=&lt;0.001), and remission status at 30 days (P=0.006) were. Fatigue was a significant predictor of ICU admission (p=0.02) whereas QOL and baseline physical function were not significant predictors. In univariate analyses, higher Charlson score was found to be a significant predictor of both ICU admission (P=0.01) and remission status at 30 days (P=0.002). Cytogenetic risk group was correlated with achievement of CR whereas neither QOL nor physical function were predictive (all P&gt;0.05). Findings were similar when the subset of 96 elderly patients (age 60+) were examined. Conclusions: Baseline QOL and physical function tests in this prospective study were not associated with short-term mortality, ICU admission, or achievement of CR after the 1 st cycle of chemotherapy.
A phase II trial evaluating tumor penetration of bortezomib in patients with recurrent malignant gliomas treated prior to surgery and then treated with bortezomib and temozolomide postoperatively.
Authors: Jeffrey J. Raizer, Sean Aaron Grimm, Robert M. Levy, Kenji Muro, Joshua M. Rosenow, James Chandler, Markus Bredel
Journal: Journal of Clinical Oncology (2012)

2035 Background: NF-Kappa B is one of the mechanisms of resistance for malignant gliomas. A few trials have assessed bortezomib in the treatment of malignant gliomas with limited activity. This may in part be due to limitations in dose escalation from peripheral neuropathy. We performed a phase II trial with the goal of measuring bortezomib in tumor tissue and also its effects on NF-Kappa B. Methods: Patients felt to be surgical candidates were enrolled after signing an IRB approved consent. They were treated with bortezomib 1.7 mg/m 2 IV on day 1, 4 and 8 and then had surgery on day 8 or 9. Approximately, 14 days post operatively, patients were started on temozolomide 75 mg/m 2 PO on days 1-7 and 14-21; on day 7 and day 21 they received bortezomib 1.7 mg/m 2 (1 cycle was 1 month). Treatment continued until progression. If &lt;1 patient had a PFS at 6 months the trial would be stopped. Results: 10 patients were enrolled (8 M and 2 F). Median age and KPS were 50 (42-64) and 90% (70-90). All but 1 patient went to surgery, one had an intracranial hemorrhage. The median number of cycles post operatively was 2 (1-4), with two patients discontinuing for wound infection (post 3 cycles, not restarted due to prolonged delays) and meningitis (post 2 cycles then withdrew from trial). Six patients are deceased. Trial was stopped as no patient had a PFS-6. PK analysis revealed measurable drug levels in tumor tissue. Conclusions: Post operative treatment with temozolomide and Bortezomib did not have any activity. Bortezomib can achieve measurable drug levels in tumor but may not be sufficient for anti-tumor activity. Tissue will be assessed for bortezomib effects on NF-Kappa B.
Surrogate endpoint in advanced hepatocellular carcinoma treated with molecular targeted therapy: Meta-analysis of randomized controlled trials.
Authors: Kyung-Hun Lee, Dae-Won Lee, Myoung-Jin Jang, Tae-Yong Kim, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Tae-You Kim
Journal: Journal of Clinical Oncology (2017)

454 Background: Time to progression (TTP) is suggested as a reliable endpoint compared to progression free survival (PFS) in the clinical trials of hepatocellular carcinoma (HCC). However, the correlation between TTP and overall survival (OS) has never been studied. Methods: We searched Pubmed and Embase data to obtain data source. Eligible studies were randomized controlled phase III trials which evaluated the efficacy of systemic chemotherapy or molecular targeted therapy in advanced HCC. The association of treatment effects as shown by the hazard ratio (HR) of TTP and OS in each trial was assessed by Spearman rank correlation coefficient ( r s ) and linear regression analysis. The association between median TTP and OS was also investigated. Results: Nine studies with a total of 18 treatment arms and 6318 patients were included. Incremental benefit from the study treatment in TTP from each trial was correlated with incremental benefit in OS. The r s value and R 2 value between log (HR TTP ) and log (HR OS ) was 0.73 (95% CI 0.12 – 0.94, p = 0.024) and 0.57. The minimum TTP effect to predict a treatment effect on OS was 0.63. Median TTP was associated with median OS. The r s value between TTP and OS was 0.73 (95% confidence interval (CI) 0.40 – 0.89, p &lt; 0.001) and the corresponding R 2 was 0.42. Conclusions: Our study results suggest that TTP could be used as a surrogate marker for OS in the clinical trials of advanced HCC. However, the results suggest modest correlation between treatment effects on TTP and OS. Along with individual-level analysis more evidences are needed to confirm our finding.
Epithelial-to-mesenchymal (EMT) markers and nanomechanical signatures of circulating tumor cells (CTC) for prediction of men with castrate-sensitive versus castration-resistant prostate cancer (PCa).
Authors: Devalingam Mahalingam, Chun-Liang Chen, Pawel A. Osmulski, Maria E Gaczynska, Ian Murchie Thompson, Tim Huang
Journal: Journal of Clinical Oncology (2014)

11045 Background: Advance PCa patients (pts) on androgen-deprivation therapy (ADT) eventually develop castrate-resistance (CR) disease. Men failing to achieve PSA ≤ 4ng/mL after 7 months of ADT have the greatest risk of early death from advance PCa. The challenge is to distinguish indolent vs. aggressive cancer, castrate sensitive (CS) vs. CR early for better disease control. During PCa progression CTC shed from tumor into bloodstream is subject to physical forces, epigenetic modifications and EMT transition. Little is known if EMT transition and the nanomechanical signatures of CTC can predict sensitivity to ADT. Methods: We obtained CTCs from 29 pts with advance PCa. CTCs were isolated from pts blood (~15 ml) using microfiltration system (ScreenCell). We analyzed CS and CR PCa cell lines, and correlated CTCs from pts with CS or CR using high throughput microfluidic single-cell RT-PCR. CTCs from 18 pts were subjected to nanomechanical analysis with atomic force microscopy (AFM) using PeakForce QNM Catalyst (Bruker). Elasticity, deformation and adhesion were evaluated as elements of nanomechanical phenotype. Results: 20pts with CR and 9pts with CS advance PCa were enrolled. Median age 65 (47-91). Median PSA 40.77 (0.1-2368.31ng/ml). A median of 1.6 (0–15) CTC/ml were detected. Increased expression of EMT genes was found in CR PCa cells and CTCs compared to CS counterparts. IPA indicated that these EMT genes are closely related to AKT, β-catenin, Myc and NFκB pathways. AFM show that CTCs of CR pts are ≥ 3 fold more elastic, ~5 fold more adherent and ~3 fold more deformable than CTCs of CS pts. Using Young modulus elasticity value <2.91 kPa, adhesion value > 120 pN and deformation value of > 412nm, combined analysis of all 3 parameters gives a > 99% power of detecting a nanomechanical phenotype of CR PCa (p=0.0002). Conclusions: CTCs isolated from CR PCa pts often lose the typical features of prostate epithelial cells, display incremental EMT-related gene expression and have a distinct nanomechanical phenotype compared to CS PCa, and could serve as biomarker for early CR detection, treatment stratification and subsequent disease monitoring.
A pilot-blinded randomized feasibility trial comparing an investigational hand therapy intervention (IHT) to a traditional occupational therapy (TOT) intervention to prevent chemotherapy induced peripheral neuropathy (CIPN) of the hands in patients (pts) receiving chemotherapy (CTX).
Authors: Gayle S. Jameson, Cynthia Cooper, Erkut Hasan Borazanci, Lynne Hull, Lana Caldwell, Daniel D. Von Hoff
Journal: Journal of Clinical Oncology (2017)

TPS518 Background: CIPN is an unsolved, common problem for cancer pts. CIPN greatly affects quality of life and may impact quantity of life due to dose reductions and discontinuation of beneficial therapy. No generally accepted evidence-based prevention strategies for CIPN exist. In the discipline of hand therapy (HT), there are effective science-based interventions to treat peripheral neuropathies due to injury and disease. These interventions have not been explored in patients with CIPN. Methods: Study objective is to determine if an IHT intervention based on concepts of neuroplasticity can prevent or delay time to onset of CIPN of the hands as measured by Patient Reported Outcomes &amp; Criteria for Adverse Events, version 4 (CTCAE 4.0), compared to a TOT intervention. Eligible pts have pancreatic cancer and receive nab-paclitaxel + gemcitabine containing combinations; have no prior evidence of peripheral neuropathy (PN) of the hands and are not taking duloxetine or gabapentin. Randomization is 1:1. Patient instructions on the blinded IHT or TOT activities are done by an Occupational Therapist prior to start of CTX, then reinforced at multiple follow-up sessions. Periodic assessments include standardized hand sensibility testing: QuickDASH, upper extremity provocative testing, TEN Test; plus pt reporting of CIPN onset, CTCAE-4, physical examination of peripheral sensory/motor neurologic assessment of the hands, Karnofsky Performance Status, and pain visual analogue scale. Participation in the study with a daily home program continues until onset of CIPN of the hands or if no CIPN then through completion of an 84 day schedule of chemotherapy. The number and proportion of patients without CIPN of the hands at the end of 84 days of CTX will be summarized for both intervention groups. For an 80% powered design with a medium effect size, 40 evaluable pts are needed (95% CI, alpha .05). Planned enrollment is up to 50 pts allowing for pt attrition. Study opened to enrollment 8/2016.
Bevacizumab plus Letrozol (LEA clinical trial phase III). Using hypertension for finding biomarkers of efficacy.
Authors: Juan de la Haba-Rodriguez, Serafin Morales, Angel Guerrero, Noelia Martinez, Antonio Martinez Peinado, Antonio Anton, Montserrat Munoz-Mateu, Jose Angel Garcia Saenz, Manuel Ramos Vazquez, Miguel J. Gil Gil, Mireia Margeli, Sonia Servitja, Begona Bermejo, Josefina Cruz Jurado, Enrique Aranda, Maribel Casas, César Rodríguez-Martín, Eva Maria Carrasco, Rosalia Caballero, Miguel Martin
Journal: Journal of Clinical Oncology (2015)

2524 Background: The LEA study compares the combination of endocrine therapy plus bevacizumab (ET-B) against endocrine therapy (ET), as first line treatment in patients (pts) with advanced breast cancer. It failed to demonstrate superiority for the combination (JCO 2015 in press). Some retrospective studies have shown that pts developing hypertension (HT) whilst on antiangiogenic treatment have a better outcome. Polymorphisms in several HT-related genes might contribute to inter-individual differences in response to these treatments. The aim of this study is to analyze the predictive value of HT for bevacizumab efficacy. Associations between polymorphisms in genes related with HT and bevacizumab efficacy were assessed. Methods: The LEA study randomized 380 pts in two treatment arms, ET-B (191 pts) and ET (189 pts). We collected Grade 1-4 HT in all pts and genotyped eleven polymorphisms in HT-related genes (ACE, AGTR1, AGT, VEGF, ADRB1, ADRB2, GNB3, NOS3) in germinal DNA from 117 of these pts (ET-B:67/ ET:50). Results: A higher rate of HT was associated with the bevacizumab combination arm (17% vs 62% pts ET vs ET-B arm, p < 0.001). Pts developing HT had a better response rate (45% vs. 27% in pts with HT vs no HT, p < 0.001), as well as a longer progression free survival (PFS) (21.9 vs 12.0 months, HR = 0.55 (95%CI:0.43–0.71), p < 0.001) and overall survival (OS) (48.6 vs 41.6 months, HR = 0.55 (95%CI:0.38–0.79), p = 0.0010). The association found between HT and ET-B, and between HT and efficacy was maintained in the genotyped subpopulation. The variant in the angiotensin converted enzyme (ACE) rs1799752 (287pbIN/DEL) and in the angiotensin receptor type 1 (AGTR1) rs5186 (M235T) were associated with HT (p < 0.05). In the ET-B arm, we found a correlation between rs1799752 ACE IN/DEL and PFS (p = 0.04), and between VEGF2578 and OS (p = 0.0045). Conclusions: HT is correlated with better clinical outcomes in pts treated with the ET-B combination. These results provide preliminary evidence of the predictive role of polymorphisms in HT-related genes in bevacizumab efficacy. The real interest of these polymorphisms should be further elucidated in larger prospective studies.