tbuckley/cabot-search huggingface dataset:
Longer-term follow up of a phase 1 study of ponatinib in patients (pts) with Philadelphia chromosome-positive (Ph+) leukemias.
Authors: Moshe Talpaz, Jorge E. Cortes, Hagop M. Kantarjian, Neil P. Shah, Dale L. Bixby, Ian Flinn, Thomas O'Hare, Simin Hu, Victor M. Rivera, Tim Clackson, Christopher D. Turner, Frank G. Haluska, Brian J Drucker, Michael W.N. Deininger, Michael J. Mauro
Journal: Journal of Clinical Oncology (2014)

7078 Background: Ponatinib is a potent oral pan–BCR-ABL TKI that is active against native and mutated forms of BCR-ABL. The safety and anti-leukemic activity of ponatinib in pts with chronic myeloid leukemia (CML) or Ph+ acute lymphoblastic leukemia were evaluated in a phase I clinical trial. Methods: Pts (N=81) with resistant/refractory hematologic malignancies were enrolled in this ongoing, open-label, dose escalation, phase I study. Ponatinib was dosed once daily (2–60 mg). 65 pts had Ph+ leukemia and are included in this analysis (data as of 15 Oct 2013). Median follow-up was 33 (0.5–57) mos. NCT00660920. Results: The median age of pts was 55 yrs; median time since diagnosis was 6.5 yrs. Pts were heavily pretreated (94% had received ≥2 prior TKIs, 62% ≥3). 65% had baseline BCR-ABL mutations (29% with T315I). 38% (58% chronic phase [CP] CML) of pts remained on study. Adverse events (AEs) and progression were the most common reasons for discontinuation in Ph+ pts (20% and 17%, respectively. The most common treatment-emergent AEs were rash (52%), fatigue (52%), abdominal pain (51%), headache (48%), arthralgia (46%). Treatment-emergent vascular occlusive events were observed in 23% (serious events) and 37% (all events) of pts, including cardiovascular, peripheral vascular, cerebrovascular, and venous thrombotic events [serious (all)] in 15% (23%), 5% (9%), 5% (8%), and 0% (5%). Significant anti-leukemic activity was observed; among CP-CML pts, major cytogenetic response (MCyR), complete cytogenetic response (CCyR), and major molecular response (MMR) rates were 72%, 65%, and 51%, respectively; 75% of pts with MCyR, 69% with CCyR, and 53% with MMR are estimated (Kaplan-Meier [KM]) to maintain response for at least 3 yrs (4 yr KM estimates: 75% MCyR, 53% MMR). Of 28 CP-CML pts with CCyR, 23 remained on study (17 with continuous CCyR); of 22 pts with MMR, 20 remained on study (12 with continuous MMR). Conclusions: Substantial and durable responses were observed with ponatinib in heavily pretreated CP-CML pts. Vascular occlusive events were observed. Risk and benefit considerations should be evaluated when utilizing ponatinib in this pt population. Clinical trial information: NCT00660920.
Is comparative effectiveness research emphasized in oncologic residency training programs? Results of a national survey.
Authors: Nicholas George Zaorsky, Jordan Hess, Robert Benjamin Den, Voichita Bar-Ad, Joanne Filicko, Adam Dicker, Timothy Norman Showalter
Journal: Journal of Clinical Oncology (2013)

e17577 Background: Comparative effectiveness research (CER) is informally defined as an assessment of all available efficacious options for a specific medical condition, with intent to estimate effectiveness and efficiency in specific subpopulations. The American Recovery and Reinvestment Act of 2009 allocated $1.8 B to increase CER and train physicians in its practice. Although program directors (PDs) of medical oncology (MO) and radiation oncology (RO) training programs know that CER is emphasized nationally, it is unknown if CER is emphasized in oncological training programs themselves. We examine the emphasis of CER in MO and RO training programs. Methods: A web-based, anonymous survey was sent to RO PDs (n = 85) and chief residents (CRs; 98); and MO PDs (99), asking them to forward a link to fellows (Fs; 160). Mean weighted Likerts (MWLs ± standard deviations [SDs]) were calculated from scales (1, strongly disagree; 3, neutral; 5, strongly agree). Results: The response rates for RO PDs, RO CRs, MO PDs, and MO Fs were 20%, 21%, 11%, and 10% (combined, 15%, 68/442). Respondents had mixed beliefs in having a clear definition of CER (MWL, 3.1 ± 1.2); their programs encouraging CER (3.2 ± 1.2); including a course on CER (2.3 ± 0.9); or discussing the differences among efficacy, effectiveness, and efficiency (2.9 ± 0.9). Retrospective cohort studies were easy to perform at institutions (4.3 ± 0.8), but less so CER (3.1 ± 1.3). Respondents believed their programs’ research integrated some core values of CER, including comparing treatments to influence clinical decision making (4.6 ± 0.7). Respondents believed CER was important (4.3 ± 0.7); 47% would divert funding from other types of research toward CER; 35% would, only if funding for other research was unaffected. Conclusions: CER is not emphasized in oncologic training programs, and most PDs and trainees cannot clearly define CER. In the era of health care reform and potential future payment reforms, it is anticipated that CER will become an increasingly important component of evidence-based medicine and continuous quality improvement. This study identifies a need for oncology training programs to incorporate education about CER into their curricula.
Plasma cytokines and angiogenic factors (CAFs) for evaluation of risk of recurrence and classification of patients (pts) with nonmetastatic renal cell carcinoma (RCC).
Authors: Mehrdad Khajavi, Eric Jonasch, Xuemei Wang, Christopher G. Wood, Surena F. Matin, Stefania Fiorentino, Kathryn S. McKee, Hai T. Tran, John Heymach, Amado J. Zurita
Journal: Journal of Clinical Oncology (2012)

e15075 Background: Although recent years have brought great progress into understanding the pathogenesis of RCC and multiple promising biomarkers, no tumor tissue or blood-based test has yet been established to assist in the clinical determination of prognosis. Whether CAFs can be used to classify RCC pts and the set of CAFs that is host vs. tumor-dependent remain unclear. The main objectives of this exploratory analysis were to identify CAFs predictive of recurrence, and to gain insight into coordinated regulation and tumor dependency of individual factors by comparing CAFs pre- and post-nephrectomy (Nx) in RCC pts. Methods: Plasma samples were obtained before and up to 1 year after Nx from 52 pts with sporadic, non-metastatic RCC with dominant clear cell histology. Pts were categorized based on pathologic staging (pT1/pT2 as low-risk [LR] for recurrence, n=32; pT3/pT4 as high-risk [HR], n=20). Multiplex bead suspension arrays and ELISA were used to measure concentrations of 58 CAFs including angiogenesis and invasion mediators (VEGF, VEGF-C, soluble CAIX [sCA9], HGF and TGF-b1, among others), and multiple inflammatory and/or immunomodulatory chemokines and interleukins (IL). t-test and Wilcoxon signed rank or rank-sum tests were respectively used to assess changes in CAFs between pre- and post-Nx or to compare CAFs between subgroups of pts. Results: The concentrations of IL-8 and sCA9, among others, were significantly higher in HR vs. LR RCC pts pre-Nx (P&lt;0.01). The pre-Nx concentrations of e-selectin were lower in RCC pts with eventual disease recurrence (P=0.027). Several CAFs decreased significantly post-Nx, including sCA9 and endoglin, whereas others increased, such as stem cell factor, IL-12, IL-18 and vascular cell adhesion molecule-1. Angiogenic and hypoxia-regulated CAFs such as OPN, sCA9, HGF, endoglin and collagen type IV grouped together using unsupervised hierarchical clustering. Conclusions: Pre-Nx CAFs associated with risk for recurrence could be useful in risk stratification of non-metastatic clear cell RCC pts. Some tumor-dependent angiogenic CAFs are coordinately regulated in these pts.
Impact of taxanes in association with anthracyclines in 1<sup>st</sup> line chemotherapy for metastatic breast cancer (MBC): Comprehensive review of 2805 patients in 7 phase III trials
Authors: E. Bria, C. Nisticò, F. Cuppone, D. Giannarelli, E. Terzoli
Journal: Journal of Clinical Oncology (2004)

659 Background: The real advantage of taxanes in adjunction to antracycline-based chemotherapy in 1st line MBC is still unclear. We performed a comprehensive review (not a meta-analysis) (Simes, Stat Med 1987) including all phase III trials of 1st line chemotherapy for MBC, to look if the combination of antracyclines (doxo- or epi-rubicin) plus taxanes (paclitaxel or docetaxel) (AT) adds some benefit over standard antracicline-based regimen (AnonT) in activity and efficacy. Methods: We included phase III (prospective and randomized) published or presented at ASCO, ESMO/ECCO between 2000 and 2003; randomized phase II were excluded. Analysis was accomplished to look at significant differences in 1) time to progression (TTP); 2) overall response rate (ORR); 3) overall survival (OS) 4) complete response rate (CR) and 5) WHO G3–4 per patient toxicity (neutropenia, febrile neutropenia, FN, cardiotoxicity and neurotoxicity). For these analyses, ratios (HR and RR) and 95% confidence intervals (CI) were derived. Results: We gathered 7 trials (3 published and 4 presented) which account overall 2806 patients (pts). Pts characteristics were similar within each trial. When AT and AnonT were pooled and compared, significant differences were seen in ORR (HR 1,36, 95% CI 1,07–1,36; data on 2805 pts), CR (RR 2,04, 95% CI 1,13–3,68; data on 2100 pts), neutropenia (RR 1,19, 95% CI 1,09–1,31; data on 2805 pts), FN (RR 2,82, 95% CI 1,01–7,84; data on 2100 pts), neurotoxicity (RR 13,2, 95% CI 1,51–114,98; data on 1892 pts). A borderline significance in favor of AT were present in TTP (HR 1,10, 95% CI 1,00–1,21; data on 2805 pts). Not significant trend in favor of AT were seen in OS (HR 1,05, 95% CI 0,90–1,22; data on 2376 pts), and cardiotoxicity (RR 3,48, 95% CI 0,68–17,72; data on 1884 pts). Conclusions: The adjunction of taxanes to antracyclines in 1st line chemotherapy for MBC pts seems to add a significant benefit in activity (ORR, CR), and a slight advantage in TTP versus standard comparator arm. OS didn't seem significantly greater. Neutropenia, FN and neurotoxicity are significantly higher. No significant financial relationships to disclose.
A systematic review and meta-analysis to evaluate the influence of surgical method on specimen margins and biochemical recurrence after radical prostatectomy for high-risk prostate cancer.
Authors: Victor Srougi, Jose Bessa, Mohammed Baghdadi, Igor Nunes-Silva, Silvia Garcia Barreras, Eric Barret, Francois Rozet, Marc Galiano, Rafael Sanchez-Salas, Xavier Cathelineau
Journal: Journal of Clinical Oncology (2017)

65 Background: To date there is no robust evidence comparing the outcomes of robotic and open radical prostatectomies in patients with high-risk prostate cancer. The purpose of this study is to perform a meta-analysis comparing the rates of positive surgical margins (PSM) and biochemical recurrence (BCR) between open radical prostatectomy (ORP) and robot-assisted radical prostatectomy (RARP) in patients with high-risk prostate cancer. Methods: A systematic review was performed on Pubmed, Embase and Scopus databases in August 2016, according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. References retrieved were evaluated using the Newcastle-Ottawa scale and the Black and Down’s tool for quality assessment. Nine retrospective cohorts comparing ORP and RARP were selected and included in the meta-analysis. Results: Nine studies reported the PSMs. Patients treated with RARP presented less risk of PSMs (risk difference -0.04, p 0.02) than those treated with ORP. Five articles reported hazard ratios for BCR-free survival. Patients treated with RARP had less risk of BCR (HR 0.72, 95% CI 0.58-0.89) than those treated with ORP. Reports for PSM assessment were considered of adequate quality, while the studies retrieved for BCR assessment were considered limited because of the heterogeneity of their results. Conclusions: Patients with high-risk prostate cancer treated with RARP have less risk of having PSM and BCR when compared to those treated with ORP. A strong conclusion is precluded due to the observational nature of the studies retrieved for our analysis.
Examining variation in mammography and breast cancer treatment quality.
Authors: Danielle Dupuy, Jennifer M. Orsi, Garth Rauscher, Anne Marie Murphy, Christine B. Weldon, Julia R. Trosman, Patricia A. Robinson, Elizabeth A. Marcus
Journal: Journal of Clinical Oncology (2012)

e16531 Background: In Chicago, Illinois, black women are 62% more likely to die from breast cancer (ca) than white women, a disparity exceeding that of the US (41%) and New York City (27%). Geographically disparate rates may suggest health system drivers of the disparity. The Chicago Breast Cancer Quality Consortium was established in 2008 to examine the quality of screening and breast cancer care to answer the question of whether variations in quality contribute to the known disparity while identify opportunities for quality improvement interventions. Methods: Mammography (mammo) screening data was collected from each site. Treatment (tx) data for each woman with a primary breast ca diagnosis who received her first course of tx at that site was collected. Measures, methods and benchmarks were developed using existing guidelines and approved by expert advisory groups. Analysis was performed to determine if sites could demonstrate they met benchmarks. Results: CY2009 aggregate screening and tx data was collected from 52 and 21 sites respectively. Only 61% (32) of sites could demonstrate that they met &gt;50% of the screening mammo benchmarks, while 76% (16) of sites could demonstrate they met &gt;50% of tx benchmarks. Conclusions: A lower proportion of sites could show they meet quality mammo benchmarks as compared to tx benchmarks. There was room for improvement in both. Further site-specific inquiry is underway to determine if results are reflective of data collection issues or actual quality issues. [Table: see text] [Table: see text]
Components of homologous recombination and translesion synthesis (TLS) in pemetrexed/cisplatin-treated non-small-cell lung cancer (NSCLC) patients (p).
Authors: Guillermo Lopez-Vivanco, Thomas Marti, Ilya N. Kotov, Imane Chaib, Santiago Ponce-Aix, Rosario García Campelo, Jose Miguel Sanchez, Angel Artal, Isabel Bover, Miquel Taron, Maria Sanchez-Ronco, Christian Diego Rolfo, Bartomeu Massuti, Rolf A. Stahel, Rafael Rosell
Journal: Journal of Clinical Oncology (2013)

11028 Background: REV3, the catalytic subunit of the TLS polymerase ξ, can continue replication past DNA adducts. Depletion of REV3 sensitizes A549 lung cancer cells to cisplatin. REV3 expression is part of a gene signature that predicted pemetrexed sensitivity in 17 NSCLC cell lines. Homologous recombination and TLS pathways have non-redundant functions in response to cisplatin. We hypothesized that low REV3 mRNA expression – alone or in combination with low expression levels of genes involved in homologous recombination – could correlate with better outcome to cisplatin/pemetrexed in NSCLC. Methods: REV3, BRCA1, RAP80, TS and AEG1 mRNA was examined by quantitative RT-PCR and categorized by terciles. Expression of each gene was correlated with outcome in 47 cisplatin/pemetrexed-treated NSCLC p. Results: 63.8% male; 47% smokers; 80.9% ECOG PS 1; 80.8% adenocarcinoma. Overall response rate was 51%, with no differences according to expression levels of any of the genes. Progression-free survival (PFS) for p with low, intermediate and high BRCA1 levels was 13.4, 5.5 and 3.9 months (m), respectively (P=0.005). Similar differences in PFS were observed according to TS (P=0.003) and AEG1 (P&lt;0.001) expression. Hazard ratio (HR) for PFS for p with high BRCA1 levels was 4 (P=0.002). Overall survival (OS) for p with low, intermediate and high BRCA1 levels was 29.7, 7.4 and 6.3 m, respectively (P=0.05). Similar differences in OS were observed according to TS (P=0.005) and AEG1 (P=0.001) expression.HR for OS for p with high BRCA1 levels was 3.6 (P=0.004). There were no differences in PFS or OS according to REV3 or RAP80 levels. However, the joint effect of BRCA1 and REV3 was significant for predictive modeling. PFS for p with low, intermediate and high levels of both genes was 14.9, 7.2 and 2.8 m, respectively (P=0.001). OS for p with low, intermediate and high levels of both genes was 29.7, 7.8 and 6.3 m, respectively (P=0.04). Conclusions: Low BRCA1 expression predicts longer PFS and OS in pemetrexed/cisplatin-treated NSCLC p. Low TS and AEG1 levels have similar predictive value. Analysis of these genes could be useful for customizing pemetrexed/platinum chemotherapy.
Differential progression-free survival (PFS) to erlotinib according to EGFR exon 19 deletion type in non-small cell lung cancer (NSCLC) patients (p) in the EURTAC study.
Authors: Enric Carcereny Costa, Miquel Taron, Cristina Queralt, Itziar de Aguirre, Laia Capdevila, Sara Cros, Alain Vergnenegre, Filippo De Marinis, Bartomeu Massuti, Noemi Reguart, Mayumi Ono, Cristina Buges, Mariano Provencio, Pilar Garrido López, Santiago Viteri Ramirez, Amaya Gasco, Jose Miguel Sanchez, Manuel Cobo, Ana Drozdowskyj, Rafael Rosell
Journal: Journal of Clinical Oncology (2012)

7540 Background: Different exon 19 deletion types have shown different in vitro sensitivity to erlotinib, with the lower IC50 for deletion E746_A750 (ELREA) (Yuza et al. Cancer Biol Ther 2007). This information prompted us to examine outcome according to type of exon 19 deletion in the EURTAC study. Methods: The EURTAC trial (clinicaltrials.gov NCT00446225) randomized 174 p with EGFR exon 19 deletions or L858R mutations to receive erlotinib or chemotherapy. Progression-free survival (PFS) was 9.7 months (m) vs 5.2 m, respectively (P&lt;0.0001). Exon 19 deletions were divided into two groups: ELREA vs non-ELREA deletions. Results: Exon 19 deletions were present in 57 p in the erlotinib arm and in 58 p in the chemotherapy arm. ELREA deletions were found in 41 p (71.9%) in the erlotinib arm and in 38 p (65.5%) in the chemotherapy arm. Non-ELREA deletions were found in 16 p in the erlotinib arm and in 20 p in the chemotherapy arm. There were no differences in p characteristics between treatment arms according to type of deletion. PFS for p with ELREA deletions was 9.4 m in the erlotinib arm and 4.6 in the chemotherapy arm (HR, 0.36; P=0.0004). PFS for p with non-ELREA deletions was not reached in p in the erlotinib arm and was 5.3 m for p in the chemotherapy arm (HR, 0.17; P=0.001). The multivariate analysis identified erlotinib arm (P&lt;0.001) and non-ELREA deletions (P=0.001) as independent markers of longer PFS. Overall survival (OS) for p with ELREA deletions was 17 m in the erlotinib arm and 18.4 in the chemotherapy arm (P=0.575). OS for p with non-ELREA deletions was not reached in the erlotinib arm and 19.5 m in the chemotherapy arm (P=0.216). Response rate (RR) for p with ELREA deletions was 53.6% in the erlotinib arm vs 15.7% in the chemotherapy arm (P=0.004). RR for p with non-ELREA deletions was 68.7% in the erlotinib arm vs 10% in the chemotherapy arm (P=0.001). Conclusions: To date, no biological reason has been identified that can explain the greater sensitivity to erlotinib in p with non-ELREA exon 19 deletions. Our findings indicate the need to define the type of deletion prior to treatment since this information can be helpful in predicting the duration of response.
Early determination of treatment sensitivity in HIV-related Hodgkin lymphoma by FDG-PET/CT after two cycles of ABVD chemotherapy: A European Cooperative Study Group on AIDS and Tumors (GECAT) study.
Authors: Nicolas Mounier, Mark Bower, Michele Spina, Caroline Besson, Clara Schiantarelli, Alessandro Re, Fabrice Bonnet, Marcus Hentrich, Christoph Wyen, Eric Van Den Neste, Irene Vandoni, Umberto Tirelli, Eugenio Borsatti
Journal: Journal of Clinical Oncology (2012)

8046 Background: The high prognostic value of FDG-PET/CT performed after 2 cycles of chemotherapy for HIV negative Hodgkin lymphoma (HL) is well known. However, experience with PET in HIV-related HL needs to be further studied as nodal FDG uptake can be observed in various opportunistic infections and AIDS-related conditions. Methods: A total of 45 consecutive HL patients (pts) were enrolled in 10 centers from the GECAT. There were 42 males and 3 females. Median age was 46 yo, range [26;64]. Median CD4 count was 391/mm 3 , range [33;1191]. Viral load was negative in 38 pts (84%) and uncontrolled in 5 pts (11%). Forthy three pts (96%) received concomitant HAART. HL was staged III-IV in 25 pts. International Prognostic Index scored 3-5 in 24 pts. All PET studies were performed after 2 ABVD cycles. They were scored, blinded to treatment outcome, according to the 5-point Deauville visual scale. It was considered as negative when scored 1-3 (i.e tumor FDG uptake less or equal than liver uptake) and positive when scored 4-5 (i.e. more than liver uptake or new lesions). Chemotherapy was not modified : 4-8 cycles of ABVD, as initially planned. Results: Overall, 35 pts (78%) achieved a CR after the end of treatment. Three pts received Involved Field Radiation Therapy. At a median follow-up of 18 months, 3 pts relapsed and 2 of them died from HL. The 2 yr OS and PFS were estimated at 94 and 90%, respectively. PET after 2 cycles of ABVD was negative in 40 pts (89%) and positive in 5 pts (11%). Patients with negative PET had a significantly better outcome than those with positive PET in term of 2 yr PFS (94% vs 60%, P=0.005), and 2 yr OS (100% vs 60%, P=0.0002). The negative predictive value was estimated at 97% and specificity at 93%. All patients who were PET-negative after the 2nd cycle stayed PET-negative after the 4th cycle and entered a durable CR. Conclusions: This largest study in HIV-positive HL showed that interim PET could play a central role in driving risk-tailored treatment. In further studies, de-escalation strategies should be tested for patients responding after 2 cycles of ABVD and those not reponding should be managed with intensive salvage strategies.