tbuckley/cabot-search huggingface dataset:
MGMT expression correlates with response rate and survival in patients with inoperable glioblastoma (GBM) treated with neoadjuvant temozolomide (TMZ)
Authors: M. Barrie, N. Eudes, P. Metellus, S. Fuentes, S. Honore, C. Boucard, H. Dufour, D. Figarella-Branger, O. Chinot
Journal: Journal of Clinical Oncology (2006)

1574 Background: Methylation of the promotor of O6-alkylguanine alkyltransferase (MGMT), a DNA repair gene, may enhance chemosensitivity to alkylating agents. In GBM, this methylation has been correlated to survival as well as to the benefit of adding TMZ concomitant and adjuvant to radiotherapy (RT) (Hegi, NEJM, 2005). We examine the relationship between MGMT expression and objective response rate to dose intense TMZ schedule administered as neoadjuvant treatment before RT in inoperable GBM, as previously presented (Chinot, ASCO, 2005). Methods: Thirty patients were included in this phase II trial that tested TMZ (150 mg/m 2 /day) on days 1 to 7 and 15 to 21 of each 28 days cycle for up to 4 cycles prior to RT. We analysed retrospectively MGMT expression by immunochemistry (streptavidin-peroxydase) after antigen retrieval using anti-MGMT antibody (Abcys, 1/100) in 25 formalin-fixed paraffin embedded samples from the study population. Results: In the eligible population (n = 28) response rates (RR) were of 25% (95% CI, 8.63% to 41.37%); SD 32%; PD 43%. Median progression free survival (PFS) and overall survival (OS) were 3.8 and 5.8 months, respectively. MGMT expression was analysed in 25 pts while material was considered as inadequate in 3 pts because of insufficient tumor material. The median percentage of cells that expressed MGMT in tumor nuclei was 35% and so was chosen as cut-off. Low MGMT expression was significantly associated with a high RR (55%) while tumor that exhibit high MGMT expression was associated to a RR of 9% (chi-2 p=0.004). MGMT was also strongly correlated to PFS (log rank p=0.009) and OS (log rank p=0.003). Conclusion: Despite limited number of patients, our study strongly supports the predictive value of MGMT expression for objective response to TMZ in addition to its prognostic value for PFS and OS in GBM. If confirmed in prospective study, MGMT expression may help to guide therapeutic decisions as well as more targeted trial design. [Table: see text] No significant financial relationships to disclose.
Comparative effectiveness trial of transoral head and neck surgery followed by adjuvant radio(chemo)therapy versus primary radiochemotherapy for oropharyngeal cancer (TopROC).
Authors: Chia-Jung Busch, Simon Laban, Claus Wittekindt, Carmen Stromberger, Silke Tribius, Christian Stephan Betz, Jens Peter Klußmann, Volker Budach, Adrian Muenscher
Journal: Journal of Clinical Oncology (2019)

TPS6093 Background: For locally advanced, transorally resectable oropharyngeal cancer (OPSCC), both, surgical resection and risk-adapted adjuvant (chemo)radiotherapy or definite chemoradiotherapy with or without salvage surgery are considered the current standard of care. To date, these two different therapeutic approaches for transorally resectable OPSCC have not been compared head to head in a randomized trial yet. The goal of this study is to compare primary transoral surgery followed by adjuvant treatment with definitive chemoradiation for resectable OPSCC, especially with regards to loco-regional control as well as organ function. Methods: TopROC is a prospective, two-arm, open label, multicenter, randomized controlled comparative effectiveness study. Eligible pts. are ≥18 years old with treatment-naïve, histologically proven OPSCC (T1, N2a-c, M0; T2, N1-2c, M0; T3, N0-2c, M0 TNM 7 th ed.) which are amenable to transoral resection, ECOG PS ≤2 and no distant metastasis. p16 immunohistochemistry by local pathology or FFPE tissue must be available for central diagnostic. 280 pts. will be randomly assigned (1:1) to surgical treatment (arm A) or chemoradiation (arm B). Standard of care treatment will be done according to daily clinical practice. Arm A consists of transoral surgical resection with neck dissection followed by risk-adapted adjuvant (chemo)radiation. Pts. treated in arm B receive standard chemoradiation, residual tumor may be subject to salvage surgery. Follow-up visits are planned until three years after treatment. Primary endpoint is time to local or locoregional failure or death from any cause (LRF). Secondary endpoints include overall and disease-free survival, toxicity, patient reported outcomes and cost-effectiveness analysis. Approximately 20 centers will be involved in Germany. This trial is supported by the German Cancer Aid and accompanied by a large scientific support program. Recruitment started in January 2018. Clinical trial information: NCT03691441.
Use of carboplatinum as neoadjuvant setting for patients affected by locally advanced cervical cancer.
Authors: Carlo De Cicco Nardone, Francesco Plotti, Michela Angelucci, Roberto Montera, Patrizio Damiani, Ester Valentina Cafà , Federica Guzzo, Maria Antonietta De Oronzo, Eva Montone, Roberto Ricciardi, Alessia Aloisi, Daniela Luvero, Rosa Alba Valentina Portuesi, Giuseppe Scaletta, Stella Capriglione, Salvatore Lopez, Andrea Miranda, Paolo Gennari, Pierluigi Benedetti Panici, Roberto Angioli
Journal: Journal of Clinical Oncology (2012)

e15553 Background: The aim of this study is to evaluate the efficacy and safety of the combination of carboplatin and paclitaxel as neoadjuvant chemotherapy (NACT) in patients affected by locally advanced cervical cancer. Methods: Between June 2007 to May 2009, all patients with diagnosis of IB2-IIB cervical cancer were considered eligible for this protocol. All enrolled patients received 3 cycles of carboplatin (AUC6) and paclitaxel at 175 mg/mq in neadjuvant setting. The chemotherapy induced toxicity and response to the treatment were evaluated according to World Health Organization criteria. Results: We have enrolled 23 patients with diagnosis of locally advanced cervical cancer. A total of 22 patients completed planned 3 cycles of neoadjuvant chemotherapy. After 3 cycles of chemotherapy 9 out of 23 patients (42%) showed a complete response, 7 patients (35%) partial response, 5 patients (16%) stable disease and 2 patients (11%) showed disease progression. The most common toxicity was haematologic (43%), extra haematologic toxicities were nausea/vomiting, neuropathy and alopecia, that occurred in 45%, 13% and 25% respectively. No renal and grade 3 and 4 haematologic toxicities were registered. Conclusions: Our results suggest that the use of carboplatin, in neadjuvant setting, is a well tolerated drug, produces manageable toxicity with a response rate similar to standard cisplatin. Then, it rappresents a valid alternative in patients affected by locally advanced cervical cancer.
A phase II biomarker assessment of tivozanib in oncology (BATON) trial in patients (pts) with advanced renal cell carcinoma (RCC).
Authors: Thomas E. Hutson, Kimryn Rathmell, Gary R. Hudes, Fairooz Kabbinavar, Nicholas J. Vogelzang, Jennifer J. Knox, C. Lance Cowey, Daniel C. Cho, Toni K. Choueiri
Journal: Journal of Clinical Oncology (2012)

TPS4686 Background: Tivozanib is an oral, potent, and selective tyrosine kinase inhibitor targeting all three vascular endothelial growth factor (VEGF) receptors; it showed efficacy and tolerability in a Phase II trial in pts with advanced RCC (Nosov et al. JCO 2011;29[18S]:4550). Preclinical studies have identified a 42-gene tivozanib resistance signature (Jie et al. EORTC-NCI-AACR 2010; abstract 608) that may be predictive of tivozanib sensitivity. This study (NCT01297244) is designed to evaluate these potential biomarkers for tivozanib activity in pts with advanced RCC. Methods: Pts with advanced RCC (stratified as clear cell or non-clear cell) who underwent nephrectomy and received ≤1 prior systemic treatment (no prior VEGF- or mammalian target of rapamycin–targeted therapy) entered this open-label, single-arm study conducted in the United States and Canada beginning January 2011. Pts receive tivozanib 1.5 mg/d orally (3 weeks on, 1 week off schedule). Primary objectives include correlation of biomarkers in blood (e.g. VEGF, hepatocyte growth factor [HGF]) and tumor tissue (e.g. CD68, hypoxia-induced factor, VEGF, HGF, and gene expression profiles) with clinical activity and/or treatment-related toxicity, and 6-month progression-free survival (PFS) rate. Secondary objectives include overall response rate (ORR), PFS, safety and tolerability, and pharmacokinetics. Contingency table methods will be used for biomarker correlation with ORR, and Cox proportional-hazards regression for correlation with PFS. Sample size (100 pts) is estimated based on clinical considerations and the precision with which 6-month PFS can be estimated. Biomarkers were defined at study outset; the requirement of prior nephrectomy ensured availability of primary tumors as controls for correlative analysis. As of January 2012, the study completed enrollment of 100 pts, demonstrating a large number of pts can be enrolled to a biomarker study with well-defined candidate genes and critical inclusion criteria to facilitate compliance. Tivozanib biomarkers evaluated in this study, along with those evaluated in other solid tumors, may play an important role in optimizing patient selection.
pH-responsive poly(lactide-co-glycolide) nanoparticles containing near-infrared dye for visualization and hyaluronic acid for treatment of osteoarthritis
Authors: L. Zerrillo, I. Que, O. Vepris, L.N. Morgado, A. Chan, K. Bierau, Y. Li, F. Galli, E. Bos, R. Censi, P. Di Martino, G.J.V.M. van Osch, L.J. Cruz
Journal: Journal of Controlled Release (2019)
Involvement of low- and middle-income countries (LMCs) in oncology randomized controlled trials (RCTs).
Authors: Janice C. Wong, Kimberly A. Fernandes, Shubarna Amin, Zarnie Lwin, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2012)

6087 Background: Lower costs and fewer regulatory barriers make clinical trials in LMCs attractive, but little is known about characteristics of such trials and roles of investigators from LMCs. We describe trends in participation of investigators from LMCs in oncology RCTs over a decade. Methods: We used Medline to identify all RCTs published in English between January 1 1998 and December 31 2008 evaluating treatment in five solid tumours (lung, breast, colorectal, stomach, liver) with high mortality in LMCs as per GLOBOCAN 2002. Data on author affiliations and roles (first, middle or corresponding author), trial characteristics, funding and study interventions were abstracted using an electronic form. Countries were stratified into low-, middle- and high-income using World Bank data. Interventions were categorized as requiring basic, limited, enhanced or maximal resources as per the Breast Health Global Initiative classification. Logistic regression identified factors associated with investigator participation from LMCs. Results: 454 trials were identified: lung (n=177), breast (n=165), colorectal (n=82), stomach (n=29), liver (n=7). The annual number of trials published increased from 10 trials in 1998 to 86 in 2008. The proportion of trials with at least one LMC author also increased over time from 20% in 1998 to 29% in 2008 (p=0.01), but almost all LMC authors were from middle-income countries. In 17% of trials involving LMC authors, they were first or corresponding authors. 67% of trials involving LMC investigators evaluated interventions requiring enhanced or maximal resources for implementation. Factors associated with LMC participation included industry funding (OR=3.57, p&lt;0.0001), use of placebo arm (OR=2.59, p=0.02) and metastatic setting (OR=3.87, p=0.0003). Conclusions: An increasing number of oncology RCTs involve LMC investigators primarily in non-leadership roles. These trials are commonly industry-funded and often test interventions that require at least enhanced resources for implementation. To minimize concerns of exploitation and facilitate future collaboration it is crucial that interventions are locally feasible and investigators receive appropriate authorship.
Expression of immunohistochemical markers in ampullary cancer (AC) and association with behavior.
Authors: Milton Jose De Barros E. Silva, Adriana Regina G. Ribeiro, Maria D. Begnami, Felipe D'Almeida Costa, Wilson Luiz Costa, Joyce Maria L. Maia, Celso Abdon Mello, Helano C. Freitas, Alessandro Landskron Diniz, Heber Salvador de Castro Ribeiro, Felipe José Fernandez Coimbra, Marcello Ferretti Fanelli
Journal: Journal of Clinical Oncology (2013)

e15184 Background: Curiously, the ampulla is formed by the union of two distinct types of mucosa: intestinal (GI) and pancreatobiliary(PB). Based on this fact, ACs could have different biologic behaviors. Methods: Between 1999 and 2012 we performed a retrospective analysis of patients with AC that underwent a pancreaticoduodenectomy (PD) with curative intent in our institution and the expressions of immunohistochemical markers related to GI origin (CK20 and CDX2) and to PB origin: (CK7 and MUC1) and its association with outcomes. Results: Twenty-seven patients underwent (PD), (M:F=15:12), median age was 62 (range33-83), 85.2% had R0 resection, 29.6% had positive lymph-nodes, 44.4% had perineural invasion, 22.2% had vascular invasion, 29.6% had lymphatic invasion, 59.2% had moderately differentiated tumors. AJCC stage pathologic grouping was: I=33.3%, II=37%, III= 29.6%; Median follow-up was 33.8 months. Relapse free survival was 43% in 3 years and overall survival was 53.7% in 5 years. The relapse rate was 59.2% and the majority of these relapses (69%) were distant metastasis without local relapse. Only positive lymph-node status (p=0,004, HR: 5.99) and R1 resection (R1: p=0.015, HR: 8.75) were independent prognostic factors for relapse on multivariate analysis. Among the patients, 21 were evaluated for the expression of immunohistochemical markers. Ten AC were classified into TGI type, 9 into PB type and 2 into unusual. An association between PB type and positive lymph node status (p=0.05) and more advanced stage (p=0.05) was found (Fisher’s exact test). There was no difference in relapse and survival between the histological subtypes, however, more PB patients had received adjuvant therapy. Conclusions: Histological subtypes of AC may have different behavior, but they are frequently neglected during decision of adjuvant therapy.
Does self-reported functional limitation attributed to symptoms persist 1 year after initial treatment for early breast cancer?
Authors: M. Sehl, W. A. Satariano, D. R. Ragland, D. B. Reuben, R. Sawhney, A. Naeim
Journal: Journal of Clinical Oncology (2007)

19519 Background and Significance: Comorbidity, disability and compromised functional status increase with age. It is unclear to what extent the symptoms related to the diagnosis and treatment of cancer play a role in activity limitation in older adults. We examined the prevalence of self-reported functional limitation in a breast cancer population, whether this limitation is attributed to various symptoms, and how this attribution changes over time from early in treatment to 9-months later. Methods: 1,011 patients with breast cancer were surveyed 3 months after diagnosis (baseline) and 933 of those patients were surveyed at 12 months after diagnosis (9 month follow up). In each survey, participants were asked whether or not they had each of 21 symptoms and whether or not each symptom caused significant activity limitation. Results: Of the 933 patients (mean age 62.7 years) who completed baseline and follow up evaluations, 420 were aged 65 years and older. At baseline, 47% of patients 65 years and older reported functional limitation compared with 44% of patients younger than 65 years (p=0.29). Activity limitation at baseline was attributed to nausea in 4% of older patients, (O) and 8% of younger patients (Y) (p=0.016), to pains in the chest area in 11% (O) and 9% (Y) (p=0.21), to joint or muscle aches in 20% (O) and 16% (Y) (p=0.13), to tiring easily in 31% (O and Y), and to depression in 9% (O) and 13% (Y) (p=0.19). At follow up 47% of patients 65 years and older reported functional limitation compared with 40% of patients younger than 65 years (p=0.02). Activity limitation at follow up was attributed to nausea in 3% (O) and 7% (Y) (p=0.003), to pains in the chest area in 11% (O) and 9% (Y) (p=0.21), to joint or muscle aches in 23% (O) and 17% (Y) (p=0.01), to tiring easily in 26% (O) and 24% (Y) (p=0.60), and to depression in 8% (O and Y). Conclusion: Self-reported functional limitation is prevalent 3 months and 1 year after breast cancer diagnosis. Self reported activity limitation in older and younger patients is not significantly different at baseline, and is significantly higher in older patients at follow up, with older patients having significantly less nausea and significantly more joint and muscle aches. No significant financial relationships to disclose.
Randomized Phase 2 Trial of Lirilumab (anti-KIR monoclonal antibody, mAb) As Maintenance Treatment in Elderly Patients (pts) with Acute Myeloid Leukemia (AML): Results of the Effikir Trial
Authors: Norbert Vey, Pierre-Yves Dumas, Christian Recher, Lauris Gastaud, Bruno Lioure, Claude-Eric Bulabois, Cecile Pautas, Jean-Pierre Marolleau, Stéphane Leprêtre, Emmanuel Raffoux, Xavier Thomas, Yosr Hicheri, Caroline Bonmati, Bruno Quesnel, Philippe Rousselot, Sylvie Castaigne, Eric Jourdan, Jean Valère Malfuson, Gaelle Guillerm, Jean Henri Bouhris, Mario Ojeda, Mathilde Hunault, Norbert Ifrah, Claude Gardin, Andre Delannoy, Lucile Beautier, Carine Paturel, Pascale Andre, Robert Zerbib, Claude Preudhomme, Antoine Toubert, Nicolas Dulphy, Daniel Olive, Arnaud Pigneux, Herve Dombret
Journal: Blood (2017)
Impact of a decision support tool on quality measures.
Authors: Peter G. Ellis, Kathleen Lokay
Journal: Journal of Clinical Oncology (2013)

6643 Background: UPMC CancerCenter received their ASCO QOPI certification after the Spring 2011 measurement period with a QOPI Certification Overall Quality Score of 78.2%. The results, however, demonstrated a number of metrics performing below QOPI mean scores. Physicians and staff performed an analysis of root causes for these underperforming metrics and identified a combination of steps to improve these metrics and the overall score. Methods: Interventions to ensure high capture of Core Metric #9 (staging within 30 days of diagnosis), #10 and #11(treatment intent and discussion with patient) were imbedded into the clinical pathways program (Via Oncology Pathways) used by the UPMC CancerCenter physicians beginning in February 2011. These data points were charted by physicians when utilizing the Via Pathways Portal and automatically displayed on the regimen order sets that are generated by that Portal. These order sets were used as official orders and therefore placed into the patient charts. Results: UPMC CancerCenter’s QOPI Certification Overall Quality Score improved by 7 percentage points to 85.39% for the Fall 2012 measurement period (as compared to Spring 2011). All of the 24 certification metrics for Fall 2012 were similar or improved as compared to Spring 2011. Core Metrics #9 and #10 improved by 18 and 22 percentage points, respectively Conclusions: Improvements in quality measures such as ASCO QOPI can be gained through targeted analysis of root cause and application of new interventions such as clinical pathways decision support. We feel that decision support tools such as pathways programs may be an important source of data for e-QOPI type programs and should be considered.
Work productivity loss in patients with tenosynovial giant cell tumors in the United States.
Authors: Feng Lin, Jackie Kwong, Raluca Ionescu-Ittu, Irina Pivneva, Willy Wynant, Sherry Shi, Eric Q. Wu, John A. Abraham
Journal: Journal of Clinical Oncology (2019)

e22527 Background: Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive and debilitating tumor that generally affects young working-age adults. This study assessed work productivity loss in TGCT patients. Methods: Incident patients aged 18-64 years with diagnosis of TGCT, who had earning and disability data, were identified in the OptumHealth database (Q1 1999 – Q1 2017). Patients were classified into surgical and non-surgical groups depending on the presence of joint surgery claim in postindex period. Control patients without TGCT were matched 10:1 with TGCT patients on age, gender, year of TGCT diagnosis, and follow-up duration. The number of days missed from work due to disability and medical visits post diagnosis was compared using Poisson regressions. General linear models were used to compare indirect costs associated with productivity loss. Results: A total of 1,395 TGCT patients (724 surgical; 671 non-surgical) were matched to 13,950 controls (36% female; mean age = 47 years). Both surgical and non-surgical TGCT patients had more comorbidities (mean Charlson Comorbidity Index (CCI): 0.3 vs 0.2; 0.4 vs 0.2; p &lt; 0.001), had greater use of analgesic drugs (44% vs 20%; 40% vs 21%; p &lt; 0.001) and MRI tests (47% vs 4%; 26% vs 3%; p &lt; 0.001) in the 12 months before TGCT diagnosis compared with controls. Both surgical and non-surgical TGCT patients missed more time from work due to disability and medical visits and had higher indirect cost associated with productivity loss than matched controls. Disability burden was greater in patients receiving surgery. Conclusions: Regardless of receiving surgery or not, TGCT is associated with significant work productivity loss. These findings highlight the unmet need for effective treatments to reduce disability and restore function in TGCT patients. [Table: see text]
Blocking HDAC3 in Bone Marrow Stromal Cells Has Direct Anti-Multiple Myeloma Effect and Modulates T Cell Function
Authors: Matthew Ho, Jiye Liu, Alireza Kalbasi, Takeshi Harada, Teru Hideshima, Paul Dowling, Yu-Tzu Tai, Li Zhang, Kenneth Wen, Ralph Mazitschek, Amanda McCann, Kenneth C Anderson, Peter O'Gorman, Giada Bianchi
Journal: Blood (2017)
Spatial Convergent Clonal Evolution Leading to Ibrutinib Resistance and Disease Progression in Chronic Lymphocytic Leukemia
Authors: Richárd Kiss, Donát Alpár, Ambrus Gángó, Noémi Nagy, Dora Aczel, Andras Matolcsy, Judit Csomor, Zoltán Mátrai, Csaba Bödör
Journal: Blood (2018)