Volume-based quantitative FDG PET/CT metrics and their association with optimal debulking and progression-free survival in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery

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Vargas, H.A.; Burger, I.A.; Micco, M.; Sosa, R.E.; Weber, W.; Hricak, H.; Sala, E. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Goldman, D.A. [Memorial Sloan Kettering Cancer Center, Department of Epidemiology and Biostatistics, New York, NY (United States); Chi, D.S. [Memorial Sloan Kettering Cancer Center, Department of Surgery, New York, NY (United States)

2015-11-15

Our aim was to evaluate the associations between quantitative {sup 18}F-fluorodeoxyglucose positron-emission tomography (FDG-PET) uptake metrics, optimal debulking (OD) and progression-free survival (PFS) in patients with recurrent ovarian cancer undergoing secondary cytoreductive surgery. Fifty-five patients with recurrent ovarian cancer underwent FDG-PET/CT within 90 days prior to surgery. Standardized uptake values (SUV{sub max}), metabolically active tumour volumes (MTV), and total lesion glycolysis (TLG) were measured on PET. Exact logistic regression, Kaplan-Meier curves and the log-rank test were used to assess associations between imaging metrics, OD and PFS. MTV (p = 0.0025) and TLG (p = 0.0043) were associated with OD; however, there was no significant association between SUV{sub max} and debulking status (p = 0.83). Patients with an MTV above 7.52 mL and/or a TLG above 35.94 g had significantly shorter PFS (p = 0.0191 for MTV and p = 0.0069 for TLG). SUV{sub max} was not significantly related to PFS (p = 0.10). PFS estimates at 3.5 years after surgery were 0.42 for patients with an MTV ≤ 7.52 mL and 0.19 for patients with an MTV > 7.52 mL; 0.46 for patients with a TLG ≤ 35.94 g and 0.15 for patients with a TLG > 35.94 g. FDG-PET metrics that reflect metabolic tumour burden are associated with optimal secondary cytoreductive surgery and progression-free survival in patients with recurrent ovarian cancer. (orig.)

Prespecified candidate biomarkers identify follicular lymphoma patients who achieved longer progression-free survival with bortezomib-rituximab versus rituximab.

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Coiffier, Bertrand; Li, Weimin; Henitz, Erin D; Karkera, Jayaprakash D; Favis, Reyna; Gaffney, Dana; Shapiro, Alice; Theocharous, Panteli; Elsayed, Yusri A; van de Velde, Helgi; Schaffer, Michael E; Osmanov, Evgenii A; Hong, Xiaonan; Scheliga, Adriana; Mayer, Jiri; Offner, Fritz; Rule, Simon; Teixeira, Adriana; Romejko-Jarosinska, Joanna; de Vos, Sven; Crump, Michael; Shpilberg, Ofer; Zinzani, Pier Luigi; Cakana, Andrew; Esseltine, Dixie-Lee; Mulligan, George; Ricci, Deborah

2013-05-01

Identify subgroups of patients with relapsed/refractory follicular lymphoma deriving substantial progression-free survival (PFS) benefit with bortezomib-rituximab versus rituximab in the phase III LYM-3001 study. A total of 676 patients were randomized to five 5-week cycles of bortezomib-rituximab or rituximab. The primary end point was PFS; this prespecified analysis of candidate protein biomarkers and genes was an exploratory objective. Archived tumor tissue and whole blood samples were collected at baseline. Immunohistochemistry and genetic analyses were completed for 4 proteins and 8 genes. In initial pairwise analyses, using individual single-nucleotide polymorphism genotypes, one biomarker pair (PSMB1 P11A C/G heterozygote, low CD68 expression) was associated with a significant PFS benefit with bortezomib-rituximab versus rituximab, controlling for multiple comparison corrections. The pair was analyzed under dominant, recessive, and additive genetic models, with significant association with PFS seen under the dominant model (G/G+C/G). In patients carrying this biomarker pair [PSMB1 P11A G allele, low CD68 expression (≤50 CD68-positive cells), population frequency: 43.6%], median PFS was 14.2 months with bortezomib-rituximab versus 9.1 months with rituximab (HR 0.47, P < 0.0001), and there was a significant overall survival benefit (HR 0.49, P = 0.0461). Response rates were higher and time to next antilymphoma therapy was longer in the bortezomib-rituximab group. In biomarker-negative patients, no significant efficacy differences were seen between treatment groups. Similar proportions of patients had high-risk features in the biomarker-positive and biomarker-negative subsets. Patients with PSMB1 P11A (G allele) and low CD68 expression seemed to have significantly longer PFS and greater clinical benefit with bortezomib-rituximab versus rituximab. ©2013 AACR.

Lactate dehydrogenase predicts combined progression-free survival after sequential therapy with abiraterone and enzalutamide for patients with castration-resistant prostate cancer.

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Mori, Keiichiro; Kimura, Takahiro; Onuma, Hajime; Kimura, Shoji; Yamamoto, Toshihiro; Sasaki, Hiroshi; Miki, Jun; Miki, Kenta; Egawa, Shin

2017-07-01

An array of clinical issues remains to be resolved for castration-resistant prostate cancer (CRPC), including the sequence of drug use and drug cross-resistance. At present, no clear guidelines are available for the optimal sequence of use of novel agents like androgen-receptor axis-targeted (ARAT) agents, particularly enzalutamide, and abiraterone. This study retrospectively analyzed a total of 69 patients with CRPC treated with sequential therapy using enzalutamide followed by abiraterone or vice versa. The primary outcome measure was the comparative combined progression-free survival (PFS) comprising symptomatic and/or radiographic PFS. Patients were also compared for total prostate-specific antigen (PSA)-PFS, overall survival (OS), and PSA response. The predictors of combined PFS and OS were analyzed with a backward-stepwise multivariate Cox model. Of the 69 patients, 46 received enzalutamide first, followed by abiraterone (E-A group), and 23 received abiraterone, followed by enzalutamide (A-E group). The two groups were not significantly different with regard to basic data, except for hemoglobin values. In a comparison with the E-A group, the A-E group was shown to be associated with better combined PFS in Kaplan-Meier analysis (P = 0.043). Similar results were obtained for total PSA-PFS (P = 0.049), while OS did not differ between groups (P = 0.62). Multivariate analysis demonstrated that pretreatment lactate dehydrogenase (LDH) values and age were significant predictors of longer combined PFS (P < 0.05). Likewise, multivariate analysis demonstrated that pretreatment hemoglobin values and performance status were significant predictors of longer OS (P < 0.05). The results of this study suggested the A-E sequence had longer combined PSA and total PSA-PFS compared to the E-A sequence in patients with CRPC. LDH values in sequential therapy may serve as a predictor of longer combined PFS. © 2017 Wiley Periodicals, Inc.

Combination of baseline metabolic tumour volume and early response on PET/CT improves progression-free survival prediction in DLBCL

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Mikhaeel, N.G.; Smith, Daniel [Guy' s and St Thomas' NHS Foundation Trust, Department of Clinical Oncology, London (United Kingdom); Dunn, Joel T.; Phillips, Michael; Barrington, Sally F. [King' s College London, PET Imaging Centre at St Thomas' Hospital, Division of Imaging Sciences and Biomedical Engineering, London (United Kingdom); Moeller, Henrik [King' s College London, Department of Cancer Epidemiology and Population Health, London (United Kingdom); Fields, Paul A.; Wrench, David [Guy' s and St Thomas' NHS Foundation Trust, Department of Haematology, London (United Kingdom)

2016-07-15

The study objectives were to assess the prognostic value of quantitative PET and to test whether combining baseline metabolic tumour burden with early PET response could improve predictive power in DLBCL. A total of 147 patients with DLBCL underwent FDG-PET/CT scans before and after two cycles of RCHOP. Quantitative parameters including metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were measured, as well as the percentage change in these parameters. Cox regression analysis was used to test the relationship between progression-free survival (PFS) and the study variables. Receiver operator characteristics (ROC) analysis determined the optimal cut-off for quantitative variables, and Kaplan-Meier survival analysis was performed. The median follow-up was 3.8 years. As MTV and TLG measures correlated strongly, only MTV measures were used for multivariate analysis (MVA). Baseline MTV (MTV-0) was the only statistically significant predictor of PFS on MVA. The optimal cut-off for MTV-0 was 396 cm{sup 3}. A model combing MTV-0 and Deauville score (DS) separated the population into three distinct prognostic groups: good (MTV-0 < 400; 5-year PFS > 90 %), intermediate (MTV-0 ≥ 400+ DS1-3; 5-year PFS 58.5 %) and poor (MTV-0 ≥ 400+ DS4-5; 5-year PFS 29.7 %) MTV-0 is an important prognostic factor in DLBCL. Combining MTV-0 and early PET/CT response improves the predictive power of interim PET and defines a poor-prognosis group in whom most of the events occur. (orig.)

Post progression survival in glioblastoma: where are we?

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Franceschi, Enrico; Ermani, Mario; Bartolini, Stefania; Bartolotti, Marco; Poggi, Rosalba; Tallini, Giovanni; Marucci, Gianluca; Fioravanti, Antonio; Tosoni, Alicia; Agati, Raffaele; Bacci, Antonella; Pozzati, Eugenio; Morandi, Luca; Balestrini, Damiano; Ghimenton, Claudio; Crisi, Girolamo; Brandes, Alba A

2015-01-01

The optimal end point for phase II studies for recurrent glioblastoma (GBM) is unclear and a matter of debate. Moreover, data about post-progression survival (PPS) after the first disease progression in GBM patients treated according to EORTC 26981/22981/NCIC CE.3 trial are limited. The aim of this study was to evaluate the PPS in GBM patients. The analysis was made with a database on 1,006 GBM patients followed prospectively between 06/2005 and 06/2010. Eligibility criteria for the study were: age ≥ 18 years; PS: 0-2; chemotherapy given at disease progression after RT/TMZ. 232 patients (mean age 52 years, range 18-77 years) were enrolled. The median PFS following second line chemotherapy (PFS2) was 2.5 months (95 % CI 2.1-2.9) and the rate of patients free of progression at 6 months (PFS2-6 mo), was 21.6 % (95 % CI 16.3-26.9 %). The median PPS was 8.6 months (95 % CI 7.4-9.8), PPS rates were: PPS-6: 66 % (95 % CI 60.3-72.9 %), PPS-9: 48.2 % (95 % CI 41.5-54.9 %) and PPS-12: 31.7 % (95 % CI 25.2-38.2 %). PPS in unselected patients treated with alkylating agents is about 8 months. PPS rates could be of interest as an end point in future studies in recurrent GBM.

Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma.

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Avet-Loiseau, Hervé; Fonseca, Rafael; Siegel, David; Dimopoulos, Meletios A; Špička, Ivan; Masszi, Tamás; Hájek, Roman; Rosiñol, Laura; Goranova-Marinova, Vesselina; Mihaylov, Georgi; Maisnar, Vladimír; Mateos, Maria-Victoria; Wang, Michael; Niesvizky, Ruben; Oriol, Albert; Jakubowiak, Andrzej; Minarik, Jiri; Palumbo, Antonio; Bensinger, William; Kukreti, Vishal; Ben-Yehuda, Dina; Stewart, A Keith; Obreja, Mihaela; Moreau, Philippe

2016-09-01

The presence of certain high-risk cytogenetic abnormalities, such as translocations (4;14) and (14;16) and deletion (17p), are known to have a negative impact on survival in multiple myeloma (MM). The phase 3 study ASPIRE (N = 792) demonstrated that progression-free survival (PFS) was significantly improved with carfilzomib, lenalidomide, and dexamethasone (KRd), compared with lenalidomide and dexamethasone (Rd) in relapsed MM. This preplanned subgroup analysis of ASPIRE was conducted to evaluate KRd vs Rd by baseline cytogenetics according to fluorescence in situ hybridization. Of 417 patients with known cytogenetic risk status, 100 patients (24%) were categorized with high-risk cytogenetics (KRd, n = 48; Rd, n = 52) and 317 (76%) were categorized with standard-risk cytogenetics (KRd, n = 147; Rd, n = 170). For patients with high-risk cytogenetics, treatment with KRd resulted in a median PFS of 23.1 months, a 9-month improvement relative to treatment with Rd. For patients with standard-risk cytogenetics, treatment with KRd led to a 10-month improvement in median PFS vs Rd. The overall response rates for KRd vs Rd were 79.2% vs 59.6% (high-risk cytogenetics) and 91.2% vs 73.5% (standard-risk cytogenetics); approximately fivefold as many patients with high- or standard-risk cytogenetics achieved a complete response or better with KRd vs Rd (29.2% vs 5.8% and 38.1% vs 6.5%, respectively). KRd improved but did not abrogate the poor prognosis associated with high-risk cytogenetics. This regimen had a favorable benefit-risk profile in patients with relapsed MM, irrespective of cytogenetic risk status, and should be considered a standard of care in these patients. This trial was registered at www.clinicaltrials.gov as #NCT01080391. © 2016 by The American Society of Hematology.

Relapsed or Refractory Double-Expressor and Double-Hit Lymphomas Have Inferior Progression-Free Survival After Autologous Stem-Cell Transplantation.

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Herrera, Alex F; Mei, Matthew; Low, Lawrence; Kim, Haesook T; Griffin, Gabriel K; Song, Joo Y; Merryman, Reid W; Bedell, Victoria; Pak, Christine; Sun, Heather; Paris, Tanya; Stiller, Tracey; Brown, Jennifer R; Budde, Lihua E; Chan, Wing C; Chen, Robert; Davids, Matthew S; Freedman, Arnold S; Fisher, David C; Jacobsen, Eric D; Jacobson, Caron A; LaCasce, Ann S; Murata-Collins, Joyce; Nademanee, Auayporn P; Palmer, Joycelynne M; Pihan, German A; Pillai, Raju; Popplewell, Leslie; Siddiqi, Tanya; Sohani, Aliyah R; Zain, Jasmine; Rosen, Steven T; Kwak, Larry W; Weinstock, David M; Forman, Stephen J; Weisenburger, Dennis D; Kim, Young; Rodig, Scott J; Krishnan, Amrita; Armand, Philippe

2017-01-01

Purpose Double-hit lymphomas (DHLs) and double-expressor lymphomas (DELs) are subtypes of diffuse large B-cell lymphoma (DLBCL) associated with poor outcomes after standard chemoimmunotherapy. Data are limited regarding outcomes of patients with relapsed or refractory (rel/ref) DEL or DHL who undergo autologous stem-cell transplantation (ASCT). We retrospectively studied the prognostic impact of DEL and DHL status on ASCT outcomes in patients with rel/ref DLBCL. Methods Patients with chemotherapy-sensitive rel/ref DLBCL who underwent ASCT at two institutions and in whom archival tumor material was available were enrolled. Immunohistochemistry for MYC, BCL2, and BCL6 and fluorescence in situ hybridization (FISH) for MYC were performed. In cases with MYC rearrangement or copy gain, FISH for BCL2 and BCL6 was also performed. Results A total of 117 patients were included; 44% had DEL and 10% had DHL. DEL and DHL were associated with inferior progression-free survival (PFS), and DHL was associated with poorer overall survival (OS). The 4-year PFS in patients with DEL compared with those with non-DEL was 48% versus 59% ( P = .049), and the 4-year OS was 56% versus 67% ( P = .10); 4-year PFS in patients with DHL compared with those with non-DHL was 28% versus 57% ( P = .013), and 4-year OS was 25% versus 61% ( P = .002). The few patients with concurrent DEL and DHL had a poor outcome (4-year PFS, 0%). In multivariable models, DEL and DHL were independently associated with inferior PFS, whereas DHL and partial response ( v complete response) at transplant were associated with inferior OS. Conclusion DEL and DHL are both associated with inferior outcomes after ASCT in patients with rel/ref DLBCL. Although ASCT remains a potentially curative approach, these patients, particularly those with DHL, are a high-risk subset who should be targeted for investigational strategies other than standard ASCT.

Evaluating Expected Costs and Benefits of Granting Access to New Treatments on the Basis of Progression-Free Survival in Non-Small-Cell Lung Cancer.

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Lakdawalla, Darius N; Chou, Jacquelyn W; Linthicum, Mark T; MacEwan, Joanna P; Zhang, Jie; Goldman, Dana P

2015-05-01

Surrogate end points may be used as proxy for more robust clinical end points. One prominent example is the use of progression-free survival (PFS) as a surrogate for overall survival (OS) in trials for oncologic treatments. Decisions based on surrogate end points may expedite regulatory approval but may not accurately reflect drug efficacy. Payers and clinicians must balance the potential benefits of earlier treatment access based on surrogate end points against the risks of clinical uncertainty. To present a framework for evaluating the expected net benefit or cost of providing early access to new treatments on the basis of evidence of PFS benefits before OS results are available, using non-small-cell lung cancer (NSCLC) as an example. A probabilistic decision model was used to estimate expected incremental social value of the decision to grant access to a new treatment on the basis of PFS evidence. The model analyzed a hypothetical population of patients with NSCLC who could be treated during the period between PFS and OS evidence publication. Estimates for delay in publication of OS evidence following publication of PFS evidence, expected OS benefit given PFS benefit, incremental cost of new treatment, and other parameters were drawn from the literature on treatment of NSCLC. Incremental social value of early access for each additional patient per month (in 2014 US dollars). For "medium-value" model parameters, early reimbursement of drugs with any PFS benefit yields an incremental social cost of more than $170,000 per newly treated patient per month. In contrast, granting early access on the basis of PFS benefit between 1 and 3.5 months produces more than $73,000 in incremental social value. Across the full range of model parameter values, granting access for drugs with PFS benefit between 3 and 3.5 months is robustly beneficial, generating incremental social value ranging from $38,000 to more than $1 million per newly treated patient per month, whereas access

Consolidation chemotherapy improves progression-free survival in stage III small-cell lung cancer following concurrent chemoradiotherapy: a retrospective study

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Chen XR

2016-09-01

Full Text Available Xin-Ru Chen,1,* Jian-Zhong Liang,2,* Shu-Xiang Ma,1 Wen-Feng Fang,1 Ning-Ning Zhou,1 Hai Liao,1 De-Lan Li,1 Li-Kun Chen1 1Department of Medical Oncology, 2Department of Pathology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China *These authors contributed equally to this work Background: Concurrent chemoradiotherapy (CCRT is the standard treatment for limited-stage small-cell lung cancer (LD-SCLC. However, the efficacy of consolidation chemotherapy (CCT in LD-SCLC remains controversial despite several studies that were performed in the early years of CCT use. The aim of this study was to reevaluate the effectiveness and toxicities associated with CCT. Methods: This retrospective analysis evaluated 177 patients with stage IIIA and IIIB small-cell lung cancer (SCLC who underwent CCRT from January 2001 to December 2013 at Sun Yat-Sen University Cancer Center (SYSUCC. Overall survival (OS and progression-free survival (PFS were analyzed using Kaplan–Meier methods. Univariate and multivariate analyses were performed to analyze patient prognosis factors. Results: Among the 177 patients, 72 (41% received CCT and 105 (59% did not receive CCT. PFS was significantly better for patients in the CCT group compared to that for patients in the non-CCT group (median PFS: 17.0 vs 12.9 months, respectively, P=0.031, whereas the differences in OS were not statistically significant (median OS: 31.6 vs 24.8 months, respectively, P=0.118. The 3- and 5-year OS rates were 33.3% and 20.8% for patients in the CCT group and 27.6% and 6.7% for patients in the non-CCT group, respectively. Multivariate analysis revealed that having a pretreatment carcinoembryonic antigen level <5 ng/mL (P=0.035, having undergone prophylactic cranial irradiation (P<0.001, and having received CCT (P=0.002 could serve as favorable independent prognostic factors

ERCC1 Cys8092Ala and XRCC1 Arg399Gln polymorphisms predict progression-free survival after curative radiotherapy for nasopharyngeal carcinoma.

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Hekun Jin

Full Text Available BACKGROUND: Single nucleotide polymorphisms (SNPs in DNA repair genes can alter gene expression and activity and affect response to cancer treatment and, correspondingly, survival. The present study was designed to evaluate the utility of the XRCC1 Arg399Gln and ERCC1 Cys8092Ala SNPs, measured in pretreatment biopsy samples, as predictors of response to radiotherapy in patients with non-metastatic nasopharyngeal carcinoma (NPC. MATERIALS AND METHODS: The study included 75 consecutive patients with stage II-IVA-B NPC. XRCC1 Arg399Glu and ERCC1 Cys8092Ala SNPs were identified from paraffin-embedded biopsy specimens via Sanger sequencing. Expression of p53 and pAkt protein was analyzed by immunohistochemical staining. Potential relationships between genetic polymorphisms and progression-free survival (PFS were analyzed by using a Cox proportional hazards model, the Kaplan-Meier method, and the log-rank test. RESULTS: Multivariate analysis showed that carriers of the ERCC1 8092 Ala/Ala genotype [hazard ratio (HR 1.882; 95% confidence interval (CI 1.031-3.438; P = 0.039] and heavy smokers (≥20 pack-years carrying the XRCC1 Arg/Arg genotype (HR 2.019; 95% CI 1.010-4.036; P = 0.047 had significantly lower PFS rates. Moreover, combined positive expression of p53 and pAkt led to significantly increased PFS in subgroups carrying the XRCC1 Gln allele (HR 7.057; 95% CI 2.073-24.021; P = 0.002 or the ERCC1 Cys allele (HR 2.568; 95% CI 1.056-6.248; P = 0.038. CONCLUSIONS: The ERCC1 Cys8092Ala polymorphism is an independent predictor of response to radiotherapy for NPC, and the XRCC1 Arg399Glu mutation combined with smoking status seems to predict PFS as well. Our results further suggest a possible correlation between these genetic polymorphisms and p53 protein status on survival.

Model-based prediction of progression-free survival in patients with first-line renal cell carcinoma using week 8 tumor size change from baseline.

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Claret, Laurent; Zheng, Jenny; Mercier, Francois; Chanu, Pascal; Chen, Ying; Rosbrook, Brad; Yazdi, Pithavala; Milligan, Peter A; Bruno, Rene

2016-09-01

To assess the link between early tumor shrinkage (ETS) and progression-free survival (PFS) based on historical first-line metastatic renal cell carcinoma (mRCC) data. Tumor size data from 921 patients with first-line mRCC who received interferon-alpha, sunitinib, sorafenib or axitinib in two Phase III studies were modeled. The relationship between model-based estimates of ETS at week 8 as well as the baseline prognostic factors and PFS was tested in multivariate log-logistic models. Model performance was evaluated using simulations of PFS distributions and hazard ratio (HR) across treatments for the two studies. In addition, an external validation was conducted using data from an independent Phase II RCC study. The relationship between expected HR of an investigational treatment vs. sunitinib and the differences in ETS was simulated. A model with a nonlinear ETS-PFS link was qualified to predict PFS distribution by ETS quartiles as well as to predict HRs of sunitinib vs. interferon-alpha and axitinib vs. sorafenib. The model also performed well in simulations of an independent study of axitinib (external validation). The simulations suggested that if a new investigational treatment could further reduce the week 8 ETS by 30 % compared with sunitinib, an expected HR [95 % predictive interval] of the new treatment vs. sunitinib would be 0.59 [0.46, 0.79]. A model has been developed that uses early changes in tumor size to predict the HR for PFS differences between treatment arms for first-line mRCC. Such a model may have utility in predicting the outcome of ongoing studies (e.g., as part of interim futility analyses), supporting early decision making and future study design for investigational agents in development for this indication.

β2 -microglobulin normalization within 6 months of ibrutinib-based treatment is associated with superior progression-free survival in patients with chronic lymphocytic leukemia.

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Thompson, Philip A; O'Brien, Susan M; Xiao, Lianchun; Wang, Xuemei; Burger, Jan A; Jain, Nitin; Ferrajoli, Alessandra; Estrov, Zeev; Keating, Michael J; Wierda, William G

2016-02-15

A high pretreatment β2 -microglobulin (B2M) level is associated with inferior survival outcomes in patients with chronic lymphocytic leukemia. However, to the authors' knowledge, the prognostic and predictive significance of changes in B2M during treatment have not been reported to date. The authors analyzed 83 patients treated with ibrutinib-based regimens (66 with recurrent/refractory disease) and 198 treatment-naive patients who were treated with combined fludarabine, cyclophosphamide, and rituximab (FCR) to characterize changes in B2M and their relationship with clinical outcomes. B2M rapidly decreased during treatment with ibrutinib; on multivariable analysis, patients who received FCR (odds ratio, 0.40; 95% confidence interval [95% CI], 0.18-0.90 [P = .027]) were less likely to have normalized B2M at 6 months than patients treated with ibrutinib. On univariable analysis, normalization of B2M was associated with superior progression-free survival (PFS) from the 6-month landmark in patients treated with ibrutinib-based regimens and FCR. On multivariable analysis, failure to achieve normalized B2M at 6 months of treatment was associated with inferior PFS (hazard ratio, 16.9; 95% CI, 1.3-220.0 [P = .031]) for patients treated with ibrutinib, after adjusting for the effects of baseline B2M, stage of disease, fludarabine-refractory disease, and del(17p). In contrast, in patients treated with FCR, negative minimal residual disease status in the bone marrow was the only variable found to be significantly associated with superior PFS (hazard ratio, 0.28; 95% CI, 0.12-0.67 [P = .004]). Normalization of B2M at 6 months in patients treated with ibrutinib was found to be a useful predictor of subsequent PFS and may assist in clinical decision-making. © 2015 American Cancer Society.

Elevated level of peripheral CD8(+)CD28(-) T lymphocytes are an independent predictor of progression-free survival in patients with metastatic breast cancer during the course of chemotherapy.

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Song, Guohong; Wang, Xiaoli; Jia, Jun; Yuan, Yanhua; Wan, Fengling; Zhou, Xinna; Yang, Huabing; Ren, Jun; Gu, Jiezhun; Lyerly, Herbert Kim

2013-06-01

Suppression of cellular immunity resulting from tumorigenesis and/or therapy might promote cancer cells' growth, progression and invasion. Here, we explored whether T lymphocyte subtypes from peripheral blood of metastatic breast cancer (MBC) female patients could be used as alternative surrogate markers for cancer progress. Additionally, plasma levels of interleukin (IL)-2, IL-4, IL-6, IL-10, IFN-γ, and transforming growth factor-β1 were quantitated from MBC and healthy volunteers. This study included 89 female MBC patients during the post-salvage chemotherapy follow-up and 50 age- and sex-matched healthy volunteers as control. The percentages of T lymphocyte subpopulations from peripheral blood and plasma levels of cytokines were measured. Both CD8(+)CD28(-) and CD4(+)CD25(+) were elevated in MBC patients compared to the control cohort (P < 0.05). In contrast, CD3(+) and CD8(+)CD28(+)cells were significantly lower in MBC patients (P < 0.0001, P = 0.045, respectively). MBC patients had elevated levels of immunosuppressive cytokines IL-6 and IL-10. Patients with elevated CD8(+)CD28(-) and CD4(+)CD25(+) cells showed increased levels of IL-6, and only patients with elevated CD8(+)CD28(-) had decreased interferon-γ. Univariate analysis indicated increased CD3(+)CD4(+) or CD8(+)CD28(+)correlated with prolonged progression-free survival (PFS), while elevated CD8(+)CD28(-)associated with shorten PFS. The percent of CD8(+)CD28(-) T lymphocytes is an independent predictor for PFS through multivariate analysis. This study suggests that progressive elevated levels of CD8(+)CD28(-) suppressor T lymphocytes represent a novel independent predictor of PFS during post-chemotherapy follow-up.

Genomic variation in myeloma: design, content, and initial application of the Bank On A Cure SNP Panel to detect associations with progression-free survival

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Fang Gang

2008-09-01

Full Text Available Abstract Background We have engaged in an international program designated the Bank On A Cure, which has established DNA banks from multiple cooperative and institutional clinical trials, and a platform for examining the association of genetic variations with disease risk and outcomes in multiple myeloma. We describe the development and content of a novel custom SNP panel that contains 3404 SNPs in 983 genes, representing cellular functions and pathways that may influence disease severity at diagnosis, toxicity, progression or other treatment outcomes. A systematic search of national databases was used to identify non-synonymous coding SNPs and SNPs within transcriptional regulatory regions. To explore SNP associations with PFS we compared SNP profiles of short term (less than 1 year, n = 70 versus long term progression-free survivors (greater than 3 years, n = 73 in two phase III clinical trials. Results Quality controls were established, demonstrating an accurate and robust screening panel for genetic variations, and some initial racial comparisons of allelic variation were done. A variety of analytical approaches, including machine learning tools for data mining and recursive partitioning analyses, demonstrated predictive value of the SNP panel in survival. While the entire SNP panel showed genotype predictive association with PFS, some SNP subsets were identified within drug response, cellular signaling and cell cycle genes. Conclusion A targeted gene approach was undertaken to develop an SNP panel that can test for associations with clinical outcomes in myeloma. The initial analysis provided some predictive power, demonstrating that genetic variations in the myeloma patient population may influence PFS.

Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

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Ruella, Marco [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, Philadelphia (United States); Filippi, Andrea Riccardo [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Bruna, Riccardo [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Di Russo, Anna [Radiation Oncology, Istituto Nazionale Tumori, Milano (Italy); Magni, Michele [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Caracciolo, Daniele [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Passera, Roberto [Division of Nuclear Medicine, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Matteucci, Paola; Di Nicola, Massimo [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Corradini, Paolo [Division of Haematology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy); Parvis, Guido [Division of Haematology, San Luigi Gonzaga Hospital, Orbassano, Torino (Italy); Gini, Guido; Olivieri, Attilio [Division of Haematology, Ospedali Riuniti, Ancona (Italy); Ladetto, Marco [Division of Haematology, San Giovanni Battista Hospital and University of Torino, Torino (Italy); Ricardi, Umberto [Department of Oncology, Radiation Oncology, University of Torino, Torino (Italy); Tarella, Corrado, E-mail: corrado.tarella@gmail.com [Division of Haematology and Cell Therapy, Mauriziano Hospital and University of Torino, Torino (Italy); Hemato-Oncology Division, European Institute of Oncology, Milano (Italy); Devizzi, Liliana [Division of Medical Oncology, Istituto Nazionale Tumori, and University of Milano, Milano (Italy)

2016-03-15

Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m{sup 2}, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

Addition of Rituximab to Involved-Field Radiation Therapy Prolongs Progression-free Survival in Stage I-II Follicular Lymphoma: Results of a Multicenter Study

International Nuclear Information System (INIS)

Ruella, Marco; Filippi, Andrea Riccardo; Bruna, Riccardo; Di Russo, Anna; Magni, Michele; Caracciolo, Daniele; Passera, Roberto; Matteucci, Paola; Di Nicola, Massimo; Corradini, Paolo; Parvis, Guido; Gini, Guido; Olivieri, Attilio; Ladetto, Marco; Ricardi, Umberto; Tarella, Corrado; Devizzi, Liliana

2016-01-01

Purpose: Rituximab (Rit) therapy added to involved-field radiation therapy (RT) has been proposed as an effective treatment for stage I-II follicular lymphoma (FL). The results of an observational multicenter study on the Rit-RT combination in limited-stage FL are here reported. Methods and Materials: Data have been collected from 2 consecutive cohorts of 94 patients with stage I-II FL treated between 1985 and 2011 at 5 Italian institutions. All patients had grade 1-3a FL, a median age of 54 years (range: 25-82). The first 51 patients received RT alone (control group), while the subsequent series of 43 patients received 4 rituximab courses (375 mg/m"2, days 1, 8, 15, 22) before RT (Rit-RT). Molecular disease was evaluated by nested bcl-2/IgH PCR or clonal IgH rearrangement was available in 33 Rit-RT patients. Results: At a median follow-up of 10.9 years (range: 1.8-22.9), the 10-year progression-free survival (PFS) and overall survival (OS) projections for the whole cohort were 57% and 87.5%, respectively. The 10-year PFS was significantly longer (P<.05) in the Rit-RT group (64.6%) compared to RT alone (50.7%), whereas the 10-year OS projections were not significantly different. On bivariate analysis controlling for stage, there was only a trend toward improved PFS for Rit-RT (HR, 0.55; P=.081). Follicular lymphoma international prognostic index and age were associated with OS but not with PFS on Cox regression analysis. Bone marrow molecular analysis showing PCR positivity at diagnosis was strongly associated with relapse risk upon univariate and multivariate analysis. Conclusions: This multicenter observational study suggests a potential benefit of adding rituximab to radiation therapy for stage I-II FL. The results of the currently ongoing randomized studies are required to confirm these results. The study underlines the importance of molecular disease monitoring also for patient with limited-stage disease.

Is there a progression-free survival benefit of first-line crizotinib versus standard chemotherapy and second-line crizotinib in ALK-positive advanced lung adenocarcinoma? A retrospective study of Chinese patients.

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Cui, Shaohua; Zhao, Yizhuo; Dong, Lili; Gu, Aiqin; Xiong, Liwen; Qian, Jialin; Zhang, Wei; Niu, Yanjie; Pan, Feng; Jiang, Liyan

2016-06-01

Although crizotinib has demonstrated promising efficacy and acceptable toxicity in patients with advanced non-small cell lung cancer (NSCLC), the available evidence in Chinese populations is currently limited. This study compared the progression-free survival (PFS) of Chinese patients with anaplastic lymphoma kinase (ALK)-positive, advanced lung adenocarcinoma who received first-line crizotinib therapy with that of patients who received first-line standard chemotherapy, and also the PFS benefit of first-line versus second-line crizotinib treatment. Data on 80 patients with ALK-positive, advanced lung adenocarcinoma who received crizotinib or standard chemotherapy as first-line treatments between June 2013 and December 2014 were retrospectively collected; 26 of the patients received crizotinib as second-line therapy after progressive disease (PD) occurred on first-line chemotherapy. Tumor responses were assessed using Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1. The median PFS was 13.3 months (95% CI: 6.5-20.0 months) in patients who received first-line crizotinib as compared with 5.4 months (95% CI: 4.4-6.5 months) in patients who received first-line standard chemotherapy (adjusted hazard ratio for progression or death with crizotinib, 0.20; 95% CI: 0.11-0.36; P benefit of first-line crizotinib versus first-line standard chemotherapy in Chinese patients with ALK-positive lung adenocarcinoma. Additionally, crizotinib showed promising efficacy in patients who received it as second-line therapy after PD had occurred on first-line chemotherapy. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Progression-free survival: gaining on overall survival as a gold standard and accelerating drug development.

Science.gov (United States)

Lebwohl, David; Kay, Andrea; Berg, William; Baladi, Jean Francois; Zheng, Ji

2009-01-01

In clinical trials of oncology drugs, overall survival (OS) is a direct measure of clinical efficacy and is considered the gold standard primary efficacy end point. The purpose of this study was to discuss the difficulties in using OS as a primary efficacy end point in the setting of evolving cancer therapies. We suggest that progression-free survival is an appropriate efficacy end point in many types of cancer, specifically those for which OS is expected to be prolonged and for which subsequent treatments are expected to affect OS.

Circulating Tumor Cells with Aberrant ALK Copy Number Predict Progression-Free Survival during Crizotinib Treatment in ALK-Rearranged Non-Small Cell Lung Cancer Patients.

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Pailler, Emma; Oulhen, Marianne; Borget, Isabelle; Remon, Jordi; Ross, Kirsty; Auger, Nathalie; Billiot, Fanny; Ngo Camus, Maud; Commo, Frédéric; Lindsay, Colin R; Planchard, David; Soria, Jean-Charles; Besse, Benjamin; Farace, Françoise

2017-05-01

The duration and magnitude of clinical response are unpredictable in ALK -rearranged non-small cell lung cancer (NSCLC) patients treated with crizotinib, although all patients invariably develop resistance. Here, we evaluated whether circulating tumor cells (CTC) with aberrant ALK -FISH patterns [ ALK -rearrangement, ALK -copy number gain ( ALK -CNG)] monitored on crizotinib could predict progression-free survival (PFS) in a cohort of ALK -rearranged patients. Thirty-nine ALK -rearranged NSCLC patients treated with crizotinib as first ALK inhibitor were recruited prospectively. Blood samples were collected at baseline and at an early time-point (2 months) on crizotinib. Aberrant ALK -FISH patterns were examined in CTCs using immunofluorescence staining combined with filter-adapted FISH after filtration enrichment. CTCs were classified into distinct subsets according to the presence of ALK -rearrangement and/or ALK -CNG signals. No significant association between baseline numbers of ALK -rearranged or ALK -CNG CTCs and PFS was observed. However, we observed a significant association between the decrease in CTC number with ALK -CNG on crizotinib and a longer PFS (likelihood ratio test, P = 0.025). In multivariate analysis, the dynamic change of CTC with ALK -CNG was the strongest factor associated with PFS (HR, 4.485; 95% confidence interval, 1.543-13.030, P = 0.006). Although not dominant, ALK -CNG has been reported to be one of the mechanisms of acquired resistance to crizotinib in tumor biopsies. Our results suggest that the dynamic change in the numbers of CTCs with ALK -CNG may be a predictive biomarker for crizotinib efficacy in ALK -rearranged NSCLC patients. Serial molecular analysis of CTC shows promise for real-time patient monitoring and clinical outcome prediction in this population. Cancer Res; 77(9); 2222-30. ©2017 AACR . ©2017 American Association for Cancer Research.

Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients

DEFF Research Database (Denmark)

Høgdall, Estrid; Fung, Eric T; Christensen, Ib Jarle

2010-01-01

To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-α trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, β-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer...

Proteomic biomarkers for overall and progression-free survival in ovarian cancer patients

DEFF Research Database (Denmark)

Høgdall, Estrid; Fung, Eric T; Christensen, Ib Jarle

2010-01-01

To determine if the level of apolipoprotein A1, hepcidin, transferrin, inter-a trypsin IV internal fragment, transthyretin (TT), connective-tissue activating protein 3 (CTAP3), serum amyloid A1, ß-2 microglobulin (B2M) might have impact on overall and progression-free survival for ovarian cancer...

Selections of appropriate regimen of high-dose chemotherapy combined with adoptive cellular therapy with dendritic and cytokine-induced killer cells improved progression-free and overall survival in patients with metastatic breast cancer: reargument of such contentious therapeutic preferences.

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Ren, Jun; Di, Lijun; Song, Guohong; Yu, Jing; Jia, Jun; Zhu, Yuling; Yan, Ying; Jiang, Hanfang; Liang, Xu; Che, Li; Zhang, Jie; Wan, Fengling; Wang, Xiaoli; Zhou, Xinna; Lyerly, Herbert Kim

2013-10-01

We hypothesized that combination of dendritic cell (DC) with autologous cytokine-induced killer (CIK) immunotherapy in setting of high-dose chemotherapy (HDC) would be effective for selected metastatic breast cancer (MBC) patients. Our previous work showed thiotepa could eradicate breast cancer stem cells. From 2004 to 2009, 79 patients received standard dose chemotherapy (SDC) of 75 mg/m(2) docetaxel and 75 mg/m(2) thiotepa versus 87 patients of HDC + DC/CIK: 120 mg/m(2) docetaxel to mobilize peripheral CD34(+) progenitor cells, a sequence of HDC (120 mg/m(2) docetaxel, plus 175 mg/m(2) thiotepa) + DC/CIK, with or without 400 mg/m(2) carboplatin depending upon bone marrow function. The endpoints were response rates (RR), progression-free survival (PFS), and overall survival (OS). Compared with SDC, PFS and OS were improved in HDC + DC/CIK (median PFS 10.2 vs. 3.7 months, P < 0.001; median OS 33.1 vs. 15.2 months, P < 0.001). Patients of pre-menopausal, HDC as first-line treatment after metastasis, or with visceral metastasis showed prolonged PFS and OS. SDC group also achieved the similar response as previous reports. Our study demonstrated the novel combination of HDC with DC/CIK to be an effective choice for the selected MBC population, in which choosing appropriate chemo regimens played important roles, and also specific HDC regimen plus DC/CIK immunotherapy showed the clinical benefits compared with chemotherapy alone.

Apparent diffusion coefficient histogram metrics correlate with survival in diffuse intrinsic pontine glioma: a report from the Pediatric Brain Tumor Consortium

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Poussaint, Tina Young; Vajapeyam, Sridhar; Ricci, Kelsey I.; Panigrahy, Ashok; Kocak, Mehmet; Kun, Larry E.; Boyett, James M.; Pollack, Ian F.; Fouladi, Maryam

2016-01-01

Background Diffuse intrinsic pontine glioma (DIPG) is associated with poor survival regardless of therapy. We used volumetric apparent diffusion coefficient (ADC) histogram metrics to determine associations with progression-free survival (PFS) and overall survival (OS) at baseline and after radiation therapy (RT). Methods Baseline and post-RT quantitative ADC histograms were generated from fluid-attenuated inversion recovery (FLAIR) images and enhancement regions of interest. Metrics assessed included number of peaks (ie, unimodal or bimodal), mean and median ADC, standard deviation, mode, skewness, and kurtosis. Results Based on FLAIR images, the majority of tumors had unimodal peaks with significantly shorter average survival. Pre-RT FLAIR mean, mode, and median values were significantly associated with decreased risk of progression; higher pre-RT ADC values had longer PFS on average. Pre-RT FLAIR skewness and standard deviation were significantly associated with increased risk of progression; higher pre-RT FLAIR skewness and standard deviation had shorter PFS. Nonenhancing tumors at baseline showed higher ADC FLAIR mean values, lower kurtosis, and higher PFS. For enhancing tumors at baseline, bimodal enhancement histograms had much worse PFS and OS than unimodal cases and significantly lower mean peak values. Enhancement in tumors only after RT led to significantly shorter PFS and OS than in patients with baseline or no baseline enhancement. Conclusions ADC histogram metrics in DIPG demonstrate significant correlations between diffusion metrics and survival, with lower diffusion values (increased cellularity), increased skewness, and enhancement associated with shorter survival, requiring future investigations in large DIPG clinical trials. PMID:26487690

Phase II study of Gleevec® plus hydroxyurea in adults with progressive or recurrent low-grade glioma1

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Reardon, David A.; Desjardins, Annick; Vredenburgh, James J.; Herndon, James E.; Coan, April; Gururangan, Sridharan; Peters, Katherine B.; McLendon, Roger; Sathornsumetee, Sith; Rich, Jeremy N.; Lipp, Eric S.; Janney, Dorothea; Friedman, Henry S.

2013-01-01

Background We evaluated the efficacy of imatinib plus hydroxyurea in patients with progressive/recurrent low-grade glioma. Methods A total of 64 patients with recurrent/progressive low-grade glioma were enrolled in this single-center study that stratified patients into astrocytoma and oligodendroglioma cohorts. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary endpoint was progression-free survival at 12 months (PFS-12) and secondary endpoints were safety, median progression-free survival and radiographic response rate. Results Thirty-two patients were enrolled into each cohort. Eleven patients (17%) had prior radiotherapy and 24 (38%) had received prior chemotherapy. The median PFS and PFS-12 were 11 months and 39%, respectively. Outcome did not differ between the histologic cohorts. No patient achieved a radiographic response. The most common grade 3 or greater adverse events were neutropenia (11%), thrombocytopenia (3%) and diarrhea (3%). Conclusions Imatinib plus hydroxyurea was well tolerated among recurrent/progressive LGG patients but this regimen demonstrated negligible anti-tumor activity. PMID:22371319

Validation of Progression‐Free Survival as a Surrogate Endpoint for Overall Survival in Malignant Mesothelioma: Analysis of Cancer and Leukemia Group B and North Central Cancer Treatment Group (Alliance) Trials

Science.gov (United States)

Wang, Xiaoyi; Hodgson, Lydia; George, Stephen L.; Sargent, Daniel J.; Foster, Nate R.; Ganti, Apar Kishor; Stinchcombe, Thomas E.; Crawford, Jeffrey; Kratzke, Robert; Adjei, Alex A.; Kindler, Hedy L.; Vokes, Everett E.; Pang, Herbert

2017-01-01

Abstract Purpose. The aim of this study was to investigate whether progression‐free survival (PFS) can be considered a surrogate endpoint for overall survival (OS) in malignant mesothelioma. Materials and Methods. Individual data were collected from 15 Cancer and Leukemia Group B (615 patients) and 2 North Central Cancer Treatment Group (101 patients) phase II trials. The effects of 5 risk factors for OS and PFS, including age, histology, performance status (PS), white blood cell count, and European Organisation for Research and Treatment of Cancer (EORTC) risk score, were used in the analysis. Individual‐level surrogacy was assessed by Kendall's tau through a Clayton bivariate Copula survival (CBCS) model. Summary‐level surrogacy was evaluated via the association between logarithms of the hazard ratio (log HR)—log HROS and log HRPFS—measured in R2 from a weighted least‐square (WLS) regression model and the CBCS model. Results. The median PFS for all patients was 3.0 months (95% confidence interval [CI], 2.8–3.5 months) and the median OS was 7.2 months (95% CI, 6.5–8.0 months). Moderate correlations between PFS and OS were observed across all risk factors at the individual level, with Kendall's tau ranging from 0.46 to 0.47. The summary‐level surrogacy varied among risk factors. The Copula R2 ranged from 0.51 for PS to 0.78 for histology. The WLS R2 ranged from 0.26 for EORTC and PS to 0.67 for age. Conclusions. The analyses demonstrated low to moderate individual‐level surrogacy between PFS and OS. At the summary level, the surrogacy between PFS and OS varied significantly across different risk factors. With a short postprogression survival and a moderate correlation between PFS and OS, there is no evidence that PFS is a valid surrogate endpoint for OS in malignant mesothelioma. Implications for Practice. For better disease management and for more efficient clinical trial designs, it is important to know if progression‐free survival (PFS) is

Magnitude of the benefit of progression-free survival as a potential surrogate marker in phase 3 trials assessing targeted agents in molecularly selected patients with advanced non-small cell lung cancer: systematic review.

Directory of Open Access Journals (Sweden)

Katsuyuki Hotta

Full Text Available BACKGROUND: In evaluation of the clinical benefit of a new targeted agent in a phase 3 trial enrolling molecularly selected patients with advanced non-small cell lung cancer (NSCLC, overall survival (OS as an endpoint seems to be of limited use because of a high level of treatment crossover for ethical reasons. A more efficient and useful indicator for assessing efficacy is needed. METHODS AND FINDINGS: We identified 18 phase 3 trials in the literature investigating EGFR-tyrosine kinase inhibitor (TKIs or ALK-TKIs, now approved for use to treat NSCLC, compared with standard cytotoxic chemotherapy (eight trials were performed in molecularly selected patients and ten using an "all-comer" design. Receiver operating characteristic analysis was used to identify the best threshold by which to divide the groups. Although trials enrolling molecularly selected patients and all-comer trials had similar OS-hazard ratios (OS-HRs (0.99 vs. 1.04, the former exhibited greater progression-free survival-hazard ratios (PFS-HR (mean, 0.40 vs. 1.01; P<0.01. A PFS-HR of 0.60 successfully distinguished between the two types of trials (sensitivity 100%, specificity 100%. The odds ratio for overall response was higher in trials with molecularly selected patients than in all-comer trials (mean: 6.10 vs. 1.64; P<0.01. An odds ratio of 3.40 for response afforded a sensitivity of 88% and a specificity of 90%. CONCLUSION: The notably enhanced PFS benefit was quite specific to trials with molecularly selected patients. A PFS-HR cutoff of ∼0.6 may help detect clinical benefit of molecular targeted agents in which OS is of limited use, although desired threshold might differ in an individual trial.

The Additional Costs per Month of Progression-Free Survival and Overall Survival: An Economic Model Comparing Everolimus with Cabozantinib, Nivolumab, and Axitinib for Second-Line Treatment of Metastatic Renal Cell Carcinoma.

Science.gov (United States)

Swallow, Elyse; Messali, Andrew; Ghate, Sameer; McDonald, Evangeline; Duchesneau, Emilie; Perez, Jose Ricardo

2018-04-01

When considering optimal second-line treatments for metastatic renal cell carcinoma (mRCC), clinicians and payers seek to understand the relative clinical benefits and costs of treatment. To use an economic model to compare the additional cost per month of overall survival (OS) and of progression-free survival (PFS) for cabozantinib, nivolumab, and axitinib with everolimus for the second-line treatment of mRCC from a third-party U.S. payer perspective. The model evaluated mean OS and PFS and costs associated with drug acquisition/administration; adverse event (AE) treatment; monitoring; and postprogression (third-line treatment, monitoring, and end-of-life costs) over 1- and 2-year horizons. Efficacy, safety, and treatment duration inputs were estimated from regimens' pivotal clinical trials; for everolimus, results were weighted across trials. Mean 1- and 2-year OS and mean 1-year PFS were estimated using regimens' reported OS and PFS Kaplan-Meier curves. Dosing and administration inputs were consistent with approved prescribing information and the clinical trials used to estimate efficacy and safety inputs. Cost inputs came from published literature and public data. Additional cost per additional month of OS or PFS was calculated using the ratio of the cost difference per treated patient and the corresponding difference in mean OS or PFS between everolimus and each comparator. One-way sensitivity analyses were conducted by varying efficacy and cost inputs. Compared with everolimus, cabozantinib, nivolumab, and axitinib were associated with 1.6, 0.3, and 0.5 additional months of PFS, respectively, over 1 year. Cabozantinib and nivolumab were associated with additional months of OS compared with everolimus (1 year: 0.7 and 0.8 months; 2 years: 1.6 and 2.3 months; respectively); axitinib was associated with fewer months (1 year: -0.2 months; 2 years: -0.7 months). The additional costs of treatment with cabozantinib, nivolumab, or axitinib versus everolimus over 1

Surrogacy of progression free survival for overall survival in metastatic breast cancer studies: Meta-analyses of published studies.

Science.gov (United States)

Kundu, Madan G; Acharyya, Suddhasatta

2017-02-01

PFS is often used as a surrogate endpoint for OS in metastatic breast cancer studies. We have evaluated the association of treatment effect on PFS with significant HR OS (and how this association is affected by other factors) in published prospective metastatic breast cancer studies. A systematic literature search in PubMed identified prospective metastatic breast cancer studies. Treatment effects on PFS were determined using hazard ratio (HR PFS ), increase in median PFS (ΔMED PFS ) and % increase in median PFS (%ΔMED PFS ). Diagnostic accuracy of PFS measures (HR PFS , ΔMED PFS and %ΔMED PFS ) in predicting significant HR OS was assessed using receiver operating characteristic (ROC) curves and classification tree approach (CART). Seventy-four cases (i.e., treatment to control comparisons) from 65 individual publications were identified for the analyses. Of these, 16 cases reported significant treatment effect on HR OS at 5% level of significance. Median number of deaths reported in these cases were 153. Area under the ROC curve (AUC) for diagnostic measures as HR PFS , ΔMED PFS and %ΔMED PFS were 0.69, 0.70 and 0.75, respectively. Classification tree results identified %ΔMED PFS and number of deaths as diagnostic measure for significant HR OS . Only 7.9% (3/39) cases with ΔMED PFS shorter than 48.27% reported significant HR OS . There were 7 cases with ΔMED PFS of 48.27% or more and number of deaths reported as 227 or more - of these 5 cases reported significant HR OS . %ΔMED PFS was found to be a better diagnostic measure for predicting significant HR OS . Our analysis results also suggest that consideration of total number of deaths may further improve its diagnostic performance. Based on our study results, the studies with 50% improvement in median PFS are more likely to produce significant HR OS if the total number of OS events at the time of analysis is 227 or more. Copyright © 2016 Elsevier Inc. All rights reserved.

Prospective, Randomized, Double-Blind, Phase III Clinical Trial of Anti-T-Lymphocyte Globulin to Assess Impact on Chronic Graft-Versus-Host Disease-Free Survival in Patients Undergoing HLA-Matched Unrelated Myeloablative Hematopoietic Cell Transplantation.

Science.gov (United States)

Soiffer, Robert J; Kim, Haesook T; McGuirk, Joseph; Horwitz, Mitchell E; Johnston, Laura; Patnaik, Mrinal M; Rybka, Witold; Artz, Andrew; Porter, David L; Shea, Thomas C; Boyer, Michael W; Maziarz, Richard T; Shaughnessy, Paul J; Gergis, Usama; Safah, Hana; Reshef, Ran; DiPersio, John F; Stiff, Patrick J; Vusirikala, Madhuri; Szer, Jeff; Holter, Jennifer; Levine, James D; Martin, Paul J; Pidala, Joseph A; Lewis, Ian D; Ho, Vincent T; Alyea, Edwin P; Ritz, Jerome; Glavin, Frank; Westervelt, Peter; Jagasia, Madan H; Chen, Yi-Bin

2017-12-20

Purpose Several open-label randomized studies have suggested that in vivo T-cell depletion with anti-T-lymphocyte globulin (ATLG; formerly antithymocyte globulin-Fresenius) reduces chronic graft-versus-host disease (cGVHD) without compromising survival. We report a prospective, double-blind phase III trial to investigate the effect of ATLG (Neovii Biotech, Lexington, MA) on cGVHD-free survival. Patients and Methods Two hundred fifty-four patients 18 to 65 years of age with acute leukemia or myelodysplastic syndrome who underwent myeloablative HLA-matched unrelated hematopoietic cell transplantation (HCT) were randomly assigned one to one to placebo (n =128 placebo) or ATLG (n = 126) treatment at 27 sites. Patients received either ATLG or placebo 20 mg/kg per day on days -3, -2, -1 in addition to tacrolimus and methotrexate as GVHD prophylaxis. The primary study end point was moderate-severe cGVHD-free survival. Results Despite a reduction in grade 2 to 4 acute GVHD (23% v 40%; P = .004) and moderate-severe cGVHD (12% v 33%; P < .001) in ATLG recipients, no difference in moderate-severe cGVHD-free survival between ATLG and placebo was found (2-year estimate: 48% v 44%, respectively; P = .47). Both progression-free survival (PFS) and overall survival (OS) were lower with ATLG (2-year estimate: 47% v 65% [ P = .04] and 59% v 74% [ P = .034], respectively). Multivariable analysis confirmed that ATLG was associated with inferior PFS (hazard ratio, 1.55; 95% CI, 1.05 to 2.28; P = .026) and OS (hazard ratio, 1.74; 95% CI, 1.12 to 2.71; P = .01). Conclusion In this prospective, randomized, double-blind trial of ATLG in unrelated myeloablative HCT, the incorporation of ATLG did not improve moderate-severe cGVHD-free survival. Moderate-severe cGVHD was significantly lower with ATLG, but PFS and OS also were lower. Additional analyses are needed to understand the appropriate role for ATLG in HCT.

Volumetric FDG-PET predicts overall and progression- free survival after 14 days of targeted therapy in metastatic renal cell carcinoma

International Nuclear Information System (INIS)

Farnebo, Jacob; Grybäck, Per; Harmenberg, Ulrika; Laurell, Anna; Wersäll, Peter; Blomqvist, Lennart K; Ullén, Anders; Sandström, Per

2014-01-01

To determine whether changes in the metabolism of metastatic renal cell carcinoma (mRCC) assessed by F18-FDG-PET after 14 and 28 days of treatment with tyrosine kinase inhibitors can predict overall and progression- free patient survival. Thirty-nine consecutive patients with mRCC were included prospectively and underwent PET examinations prior to and after 14 and 28 days of standard treatment with sunitinib (n = 18), sorafenib (n = 19) or pazopanib (n = 2). The PET response was analyzed in terms of SUVmax, SULpeak, and total lesion glycolysis and a positive response (defined as a 30% reduction) compared to overall and progression- free survival. Thirty-five patients with at least one metabolically active metastatic lesion prior to treatment underwent additional FDG-PET examinations after 14 (n = 32) and/or 28 days (n = 30) of treatment. Changes in either SULpeak or total lesion glycolysis were correlated to both progression-free and overall survival (for TLG2.5 responders, HR = 0.38 (95% CI: 0.18-0.83) and 0.22 (95% CI: 0.09-0.53), and for TLG50 responders, HR = 0.25 (0.10-0.62) and 0.25 (95% CI: 0.11-0.57) and for SULpeak responders, HR = 0.39 (95% CI: 0.17-0.91) and 0.38 (95% CI: 0.15-0.93), respectively). In contrast SUVmax response did not predict progression- free or overall survival (HR = 0.43 (95% CI: 0.18-1.01) and 0.50 (95% CI: 0.21-1.19), respectively). Assessment of early changes in SULpeak and total lesion glycolysis undergoing treatment with tyrosine kinase inhibitors by FDG-PET can possibly predict progression- free and overall survival in patients with mRCC

Progression-free survival results in postmenopausal Asian women: subgroup analysis from a phase III randomized trial of fulvestrant 500 mg vs anastrozole 1 mg for hormone receptor-positive advanced breast cancer (FALCON).

Science.gov (United States)

Noguchi, Shinzaburo; Ellis, Matthew J; Robertson, John F R; Thirlwell, Jackie; Fazal, Mehdi; Shao, Zhimin

2018-05-01

The international, phase III FALCON study (NCT01602380) in postmenopausal patients with hormone receptor-positive, locally advanced/metastatic breast cancer (LA/MBC) who had not received prior endocrine therapy, demonstrated statistically significant improvement in progression-free survival (PFS) for patients who received fulvestrant 500 mg vs anastrozole 1 mg. This subgroup analysis evaluated PFS in Asian (randomized in China, Japan, or Taiwan) and non-Asian patients from the FALCON study. Eligible patients (estrogen receptor- and/or progesterone receptor-positive LA/MBC; World Health Organization performance status 0-2; ≥ 1 measurable/non-measurable lesion[s]) were randomized. PFS was assessed via Response Evaluation Criteria in Solid Tumours version 1.1, surgery/radiotherapy for disease worsening, or death (any cause). Secondary endpoints included: objective response rate, clinical benefit rate, duration of response, and duration of clinical benefit. Consistency of effect across subgroups was assessed via hazard ratios and 95% confidence intervals (CIs) using a log-rank test. Adverse events (AEs) were evaluated. Of the 462 randomized patients, the Asian and non-Asian subgroups comprised 67 and 395 patients, respectively. In the Asian subgroup, median PFS was 16.6 and 15.9 months with fulvestrant and anastrozole, respectively (hazard ratio 0.81; 95% CI 0.44-1.50). In the non-Asian subgroup, median PFS was 16.5 and 13.8 months, respectively (hazard ratio 0.79; 95% CI 0.62-1.01). Secondary outcomes were numerically improved with fulvestrant vs anastrozole in both subgroups. AE profiles were generally consistent between Asian and non-Asian subgroups. Results of this subgroup analysis suggest that treatment effects in the Asian patient subgroup are broadly consistent with the non-Asian population.

Maintenance Therapy in Ovarian Cancer with Targeted Agents Improves PFS and OS: A Systematic Review and Meta-Analysis.

Directory of Open Access Journals (Sweden)

Xinyu Qian

Full Text Available Maintenance therapy with targeted agents for prolonging remission for ovarian cancer patients remains controversial. As a result, a meta-analysis was conducted to assess the effectiveness and safety of using maintenance therapy with targeted agents for the treatment of ovarian cancer.From inception to January 2015, we searched for randomized, controlled trials (RCTs using the following databases: PubMed, ScienceDirect, the Cochrane Library, Clinicaltrials.gov and EBSCO. Eligible trials included RCTs that evaluated standard chemotherapy which was either followed or not followed by targeted maintenance in patients with ovarian cancer who had been previously receiving adjunctive treatments, such as cytoreductive surgery and standard chemotherapy. The outcome measures included progression-free survival (PFS, overall survival (OS and incidence of adverse events.A total of 13 RCTs, which were published between 2006 and 2014, were found to be in accordance with our inclusion criteria. The primary meta-analysis indicated that both PFS and OS were statistically and significantly improved in the targeted maintenance therapy group as compared to the control group (PFS: HR = 0.84, 95%CI: 0.75 to 0.95, p = 0.001; OS: HR = 0.91, 95%CI: 0.84 to 0.98, p = 0.02. When taking safety into consideration, the use of targeted agents was significantly correlated with increased risks of fatigue, diarrhea, nausea, vomiting, and hypertension. However, no significant differences were found in incidence rates of abdominal pain, constipation or joint pain.Our results indicate that targeted maintenance therapy clearly improves the survival of ovarian cancer patients but may also increase the incidence of adverse events. Additional randomized, double-blind, placebo-controlled, multicenter investigations will be required on a larger cohort of patients to verify our findings.

Polymorphisms associated with everolimus pharmacokinetics, toxicity and survival in metastatic breast cancer.

Directory of Open Access Journals (Sweden)

Tomas Pascual

Full Text Available Metastatic breast cancer (MBC progressing after endocrine therapy frequently activates PI3K/AKT/mTOR pathway. The BOLERO-2 trial showed that everolimus-exemestane achieves increased progression free survival (PFS compared with exemestane. However, there is great inter-patient variability in toxicity and response to exemestane-everolimus treatment. The objective of this study was to perform an exploratory study analyzing the implication of single nucleotide polymorphisms (SNPs on outcomes from this treatment through a pharmacogenetic analysis.Blood was collected from 90 postmenopausal women with hormone receptor-positive, HER2-negative MBC treated with exemestane-everolimus following progression after prior treatment with a non-steroidal aromatase inhibitor. Everolimus pharmacokinetics was measured in 37 patients. Twelve SNPs in genes involved in everolimus pharmacokinetics and pharmacodynamics were genotyped and associations assessed with drug plasma levels, clinically relevant toxicities (non-infectious pneumonitis, mucositis, hyperglycemia and hematological toxicities, dose reductions or treatment suspensions due to toxicity, progression free survival (PFS and overall survival.We found that CYP3A4 rs35599367 variant (CYP3A4*22 allele carriers had higher everolimus blood concentration compared to wild type patients (P = 0.019. ABCB1 rs1045642 was associated with risk of mucositis (P = 0.031, while PIK3R1 rs10515074 and RAPTOR rs9906827 were associated with hyperglycemia and non-infectious pneumonitis (P = 0.016 and 0.024, respectively. Furthermore, RAPTOR rs9906827 was associated with PFS (P = 0.006.CYP3A4*22 allele influenced plasma concentration of everolimus and several SNPs in PI3K/AKT/mTOR pathway genes were associated with treatment toxicities and prognosis. These results require replication, but suggest that germline variation could influence everolimus outcomes in MBC.

PSA response to cabazitaxel is associated with improved progression-free survival in metastatic castration-resistant prostate cancer: the non-interventional QoLiTime study.

Science.gov (United States)

Hammerer, Peter; Al-Batran, Salah-Eddin; Windemuth-Kieselbach, Christine; Keller, Martin; Hofheinz, Ralf-Dieter

2018-03-01

To evaluate the association between prostate-specific antigen (PSA) response and progression-free and overall survival in men with metastatic castration-resistant prostate cancer (mCRPC) treated with cabazitaxel. Men with mCRPC receiving cabazitaxel (25 mg/m 2 , every 3 weeks) plus oral prednis(ol)one (10 mg/day) were enrolled in the non-interventional, prospective QoLiTime study. Main outcome measures were progression-free survival and overall survival, in all patients and in those who showed a ≥ 50 or a ≥ 30% decrease in PSA relative to baseline after four cycles of cabazitaxel, as well as quality-of-life parameters. Of the 527 men (median age 72 years), 266 received ≥ 4 cycles of cabazitaxel and had PSA response data. After four cycles, 34.6% of men achieved a PSA decrease ≥ 50% and 49.6% a decrease ≥ 30%. Median progression-free survival was 7.7 (95% CI 6.2, 9.5) months, and overall survival was 19.5 (95% CI 16.0, 30.9) months, corresponding to 1-year event rates of 39.4 and 78.8%, respectively. Median progression-free survival was longer in PSA responders versus non-responders (15.7 vs 5.5 months at 50% cut-off; 15.7 vs 5.3 months for 30% cut-off; both P PSA response after four cycles of cabazitaxel is associated with improved progression-free survival in men with mCRPC treated with cabazitaxel plus prednis(ol)one.

A phase II trial with bevacizumab and irinotecan for patients with primary brain tumors and progression after standard therapy

DEFF Research Database (Denmark)

Møller, Søren; Grunnet, Kirsten; Hansen, Steinbjørn

2012-01-01

The combination of irinotecan and bevacizumab has shown efficacy in the treatment of recurrent glioblastoma multiforme (GBM). A prospective, phase II study of 85 patients with various recurrent brain tumors was carried out. Primary endpoints were progression free survival (PFS) and response rate....

Weight Gain in Advanced Non-Small-Cell Lung Cancer Patients During Treatment With Split-Course Concurrent Chemoradiotherapy Is Associated With Superior Survival

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Gielda, Benjamin T., E-mail: Benjamin_gielda@rush.edu [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Mehta, Par [Department of Radiation Oncology at Rush Copley Medical Center, Aurora, IL (United States); Khan, Atif [Department of Radiation Oncology, University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School and Cancer Institute of New Jersey, New Brunswick, NJ (United States); Marsh, James C.; Zusag, Thomas W. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Warren, William H. [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, IL (United States); Fidler, Mary Jo [Section of Medical Oncology, Rush University Medical Center, Chicago, IL (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Bonomi, Philip [Section of Medical Oncology, Rush University Medical Center, Chicago, IL (United States); Liptay, Michael; Faber, L. Penfield [Department of Cardiothoracic Surgery, Rush University Medical Center, Chicago, IL (United States)

2011-11-15

Background: Preoperative concurrent chemoradiotherapy (CRT) is an accepted treatment for potentially resectable, locally advanced, non-small-cell lung cancer (NSCLC). We reviewed a decade of single institution experience with preoperative split-course CRT followed by surgical resection to evaluate survival and identify factors that may be helpful in predicting outcome. Methods and Materials: All patients treated with preoperative split-course CRT and resection at Rush University Medical Center (RUMC) between January 1999 and December 2008 were retrospectively analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), local-regional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS). Patient and treatment related variables were assessed for correlation with outcomes. Results: A total of 54 patients were analyzed, 76% Stage IIIA, 18% Stage IIIB, and 6% oligometastatic. The pathologic complete response (pCR) rate was 31.5%, and the absence of nodal metastases (pN0) was 64.8%. Median OS and 3-year actuarial survival were 44.6 months and 50%, respectively. Univariate analysis revealed initial stage (p < 0.01) and percent weight change during CRT (p < 0.01) significantly correlated with PFS/OS. On multivariate analysis initial stage (HR, 2.4; 95% CI, 1.18-4.90; p = 0.02) and percent weight change (HR, 0.79; 95% CI, 0.67-0.93; p < 0.01) maintained significance with respect to OS. There were no cases of Grade 3+ esophagitis, and there was a single case of Grade 3 febrile neutropenia. Conclusions: The strong correlation between weight change during CRT and OS/PFS suggests that this clinical parameter may be useful as a complementary source of predictive information in addition to accepted factors such as pathological response.

Progression-free Survival Following Stereotactic Body Radiotherapy for Oligometastatic Prostate Cancer Treatment-naive Recurrence: A Multi-institutional Analysis.

Science.gov (United States)

Ost, Piet; Jereczek-Fossa, Barbara Alicja; As, Nicholas Van; Zilli, Thomas; Muacevic, Alexander; Olivier, Kenneth; Henderson, Daniel; Casamassima, Franco; Orecchia, Roberto; Surgo, Alessia; Brown, Lindsay; Tree, Alison; Miralbell, Raymond; De Meerleer, Gert

2016-01-01

The literature on metastasis-directed therapy for oligometastatic prostate cancer (PCa) recurrence consists of small heterogeneous studies. This study aimed to reduce the heterogeneity by pooling individual patient data from different institutions treating oligometastatic PCa recurrence with stereotactic body radiotherapy (SBRT). We focussed on patients who were treatment naive, with the aim of determining if SBRT could delay disease progression. We included patients with three or fewer metastases. The Kaplan-Meier method was used to estimate distant progression-free survival (DPFS) and local progression-free survival (LPFS). Toxicity was scored using the Common Terminology Criteria for Adverse Events. In total, 163 metastases were treated in 119 patients. The median DPFS was 21 mo (95% confidence interval, 15-26 mo). A lower radiotherapy dose predicted a higher local recurrence rate with a 3-yr LPFS of 79% for patients treated with a biologically effective dose ≤100Gy versus 99% for patients treated with >100Gy (p=0.01). Seventeen patients (14%) developed toxicity classified as grade 1, and three patients (3%) developed grade 2 toxicity. No grade ≥3 toxicity occurred. These results should serve as a benchmark for future prospective trials. This multi-institutional study pools all of the available data on the use of stereotactic body radiotherapy for limited prostate cancer metastases. We concluded that this approach is safe and associated with a prolonged treatment progression-free survival. Copyright © 2015. Published by Elsevier B.V.

Frontline low-dose alemtuzumab with fludarabine and cyclophosphamide prolongs progression-free survival in high-risk CLL

DEFF Research Database (Denmark)

Geisler, Christian H; van T' Veer, Mars B; Jurlander, Jesper

2014-01-01

.3%). FCA improves progression-free survival in high-risk chronic lymphocytic leukemia. As anticipated, FCA is more immunosuppressive than FC, but with due vigilance, does not lead to a higher treatment-related mortality. This study was registered at www.trialregister.nl as trial no. NTR529....

Influence of tumor grade on time to progression after irradiation for localized ependymoma in children

International Nuclear Information System (INIS)

Merchant, Thomas E.; Jenkins, Jesse J.; Burger, Peter C.; Sanford, Robert A.; Sherwood, Scot H.; Jones-Wallace, Dana; Heideman, Richard L.; Thompson, Stephen J.; Helton, Kathleen J.; Kun, Larry E.

2002-01-01

Purpose: To investigate the influence of histologic grade on progression-free survival (PFS) after irradiation (RT) for pediatric patients with localized ependymoma. Methods and Materials: Fifty patients with localized ependymoma (median age 3.6 years, range 1-18 years at the time of RT) were treated with RT between December 1982 and June 1999. Anaplastic features were identified in 14 of 50 patients. The extent of resection was characterized as gross-total in 36 patients, near-total in 5, and subtotal in 9. The median dose to the primary site was 54 Gy. Of the 50 patients, 23 received pre-RT chemotherapy. Results: Thirty-nine patients were alive at a median follow-up of 46 months (range 21-214) from diagnosis. Thirty-four patients remained progression free at a median follow-up of 35 months (range 13-183) after the initiation of RT. Progression occurred in 16 patients (12 local and 4 local and distant), with a median time to failure of 21.2 months (range 4.6-65.0). The tumor grade significantly influenced the PFS after RT (p<0.0005). The estimated 3-year PFS rate was 28%±14% for patients with anaplastic ependymoma compared with 84% ± 8% for patients with differentiated ependymoma. These results remained significant when corrected for age at diagnosis (<3 years), pre-RT chemotherapy, and extent of resection. Patients who received pre-RT chemotherapy had an inferior 3-year PFS estimate after RT (49±12%) compared with those who did not (84%±10%; p=0.056). Anaplastic ependymoma was found more frequently in the supratentorial brain (p=0.002). Six of 12 patients with supratentorial tumor developed recurrence; recurrence was restricted to patients with anaplastic ependymoma. Conclusion: Tumor grade influences outcome for patients with ependymoma independent of other factors and should be considered in the design and analysis of prospective trials involving pediatric patients treated with RT. Chemotherapy before RT influences the PFS and overall survival after RT. The

N-Terminal Prodomain of Pfs230 Synthesized Using a Cell-Free System Is Sufficient To Induce Complement-Dependent Malaria Transmission-Blocking Activity▿

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Tachibana, Mayumi; Wu, Yimin; Iriko, Hideyuki; Muratova, Olga; MacDonald, Nicholas J.; Sattabongkot, Jetsumon; Takeo, Satoru; Otsuki, Hitoshi; Torii, Motomi; Tsuboi, Takafumi

2011-01-01

The aim of a malaria transmission-blocking vaccine is to block the development of malaria parasites in the mosquito and thus prevent subsequent infection of the human host. Previous studies have demonstrated that the gametocyte/gamete surface protein Pfs230 can induce transmission-blocking immunity and have evaluated Escherichia coli-produced Pfs230 as a transmission-blocking vaccine candidate. In this study, we used the wheat germ cell-free expression system to produce N-terminal fragments of Pfs230 and evaluated the transmission-blocking activity of antisera raised against the recombinant Pfs230 protein. The rabbit antisera reacted to the surface of cultured gametocytes and gametes of the Plasmodium falciparum NF54 line, recognized the 360-kDa form of parasite-produced Pfs230 by Western blot assay, and reduced the infectivity of NF54 parasites to Anopheles stefensi mosquitoes in the presence of complement in a standard membrane feeding assay. Thus, our data demonstrate that the N-terminal pro domain of Pfs230 is sufficient to induce complement-dependent transmission-blocking activity against P. falciparum. PMID:21715579

N-terminal prodomain of Pfs230 synthesized using a cell-free system is sufficient to induce complement-dependent malaria transmission-blocking activity.

Science.gov (United States)

Tachibana, Mayumi; Wu, Yimin; Iriko, Hideyuki; Muratova, Olga; MacDonald, Nicholas J; Sattabongkot, Jetsumon; Takeo, Satoru; Otsuki, Hitoshi; Torii, Motomi; Tsuboi, Takafumi

2011-08-01

The aim of a malaria transmission-blocking vaccine is to block the development of malaria parasites in the mosquito and thus prevent subsequent infection of the human host. Previous studies have demonstrated that the gametocyte/gamete surface protein Pfs230 can induce transmission-blocking immunity and have evaluated Escherichia coli-produced Pfs230 as a transmission-blocking vaccine candidate. In this study, we used the wheat germ cell-free expression system to produce N-terminal fragments of Pfs230 and evaluated the transmission-blocking activity of antisera raised against the recombinant Pfs230 protein. The rabbit antisera reacted to the surface of cultured gametocytes and gametes of the Plasmodium falciparum NF54 line, recognized the 360-kDa form of parasite-produced Pfs230 by Western blot assay, and reduced the infectivity of NF54 parasites to Anopheles stefensi mosquitoes in the presence of complement in a standard membrane feeding assay. Thus, our data demonstrate that the N-terminal pro domain of Pfs230 is sufficient to induce complement-dependent transmission-blocking activity against P. falciparum.

Combined high-field intraoperative magnetic resonance imaging and endoscopy increase extent of resection and progression-free survival for pituitary adenomas

Science.gov (United States)

Sylvester, Peter T.; Evans, John A.; Zipfel, Gregory J.; Chole, Richard A.; Uppaluri, Ravindra; Haughey, Bruce H.; Getz, Anne E.; Silverstein, Julie; Rich, Keith M.; Kim, Albert H.; Dacey, Ralph G.

2014-01-01

Purpose The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and subtotal resection), and operative complications. Methods Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. Results Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21–3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24–6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00–4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). Conclusions Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact

Medulloblastoma: progress over time

International Nuclear Information System (INIS)

Smee, Robert I.; Williams, Janet R.; De-loyde, Katie J.; Meagher, Nicola S.; Cohn, Richard

2012-01-01

Medulloblastoma is the most common central nervous system tumour in children aged 0–4 years, with 75% of cases occurring in patients <16 years, and rare in adults. The intent of this audit is to review a single centre's experience and to compare outcomes with other centres' outcomes. This Ethics approved retrospective audit evaluates the paediatric population aged <16 years who received radiotherapy as their initial or salvage treatment at the Prince of Wales Hospital Cancer Centre between 1972 and 2007. The primary and secondary end-points were progression-free survival (PFS) and cancer-specific survival (CSS), with comparisons made between patients treated before and after 1990, and the impact of high- and low-risk disease. There were 80 eligible patients, 78 who had radiotherapy at initial presentation, and 2 at the time of recurrence. Median age was 6.5 years, 52 were boys and 28 were girls. Seventy-eight patients had a surgical procedure and ultimately received craniospinal radiotherapy. Of these 78 patients, 32 (40%) had a macroscopically complete resection. The 5-year PFS was 69.7%. The 5-year PFS for patients treated pre and post 1990 was 66.1% and 71.8%, respectively. The 5-year CSS for high- and low-risk patients was 61.1% and 78.4%, respectively. Ultimately, 33% of patients were dead due to disease. This audit demonstrates those children referred to this facility for treatment have comparable survival to that of other major centres.

Intensity-modulated radiotherapy prolongs the survival of patients with nasopharyngeal carcinoma compared with conventional two-dimensional radiotherapy: A 10-year experience with a large cohort and long follow-up.

Science.gov (United States)

Zhang, Meng-Xia; Li, Jing; Shen, Guo-Ping; Zou, Xiong; Xu, Jun-Jie; Jiang, Rou; You, Rui; Hua, Yi-Jun; Sun, Ying; Ma, Jun; Hong, Ming-Huang; Chen, Ming-Yuan

2015-11-01

To evaluate the survival benefit of intensity-modulated radiotherapy (IMRT) compared with conventional two-dimensional radiotherapy (2D-CRT) in nasopharyngeal carcinoma (NPC) using a large cohort with long follow-up. We retrospectively analysed 7081 non-metastatic NPC patients who received curative IMRT or 2D-CRT from February 2002 to December 2011. Of the 7081 patients, 2245 (31.7%) were administered IMRT, while 4836 (68.3%) were administered 2D-CRT. At 5 years, the patients administered IMRT had significantly higher local relapse-free survival (LRFS), loco-regional relapse-free survival (LRRFS), progression-free survival (PFS) and overall survival (OS) (95.6%, 92.5%, 82.1% and 87.4%, respectively) than those administered 2D-CRT (90.8%, 88.5%, 76.7% and 84.5%, respectively; p<0.001). The distant metastasis-free survival (DMFS) was higher for IMRT than 2D-CRT, with borderline significance (87.6% and 85.7%, respectively; p=0.056). However, no difference was observed between IMRT and 2D-CRT in nodal relapse-free survival (NRFS; 96.3% and 97.4%, respectively; p=0.217). Multivariate analyses showed that IMRT was an independent protective prognostic factor for LRFS, LRRFS and PFS, but not NRFS, DMFS or OS. IMRT provided an improved LRFS, LRRFS and PFS in both the early and advanced T classifications and overall stage for non-disseminated NPC compared with 2D-CRT. However, no significant advantage was observed in NRFS, DMFS or OS when IMRT was used. Copyright © 2015 Elsevier Ltd. All rights reserved.

Hope, optimism and survival in a randomised trial of chemotherapy for metastatic colorectal cancer.

Science.gov (United States)

Schofield, Penelope E; Stockler, M R; Zannino, D; Tebbutt, N C; Price, T J; Simes, R J; Wong, N; Pavlakis, N; Ransom, D; Moylan, E; Underhill, C; Wyld, D; Burns, I; Ward, R; Wilcken, N; Jefford, M

2016-01-01

Psychological responses to cancer are widely believed to affect survival. We investigated associations between hope, optimism, anxiety, depression, health utility and survival in patients starting first-line chemotherapy for metastatic colorectal cancer. Four hundred twenty-nine subjects with metastatic colorectal cancer in a randomised controlled trial of chemotherapy completed baseline questionnaires assessing the following: hopefulness, optimism, anxiety and depression and health utility. Hazard ratios (HRs) and P values were calculated with Cox models for overall survival (OS) and progression-free survival (PFS) in univariable and multivariable analyses. Median follow-up was 31 months. Univariable analyses showed that OS was associated negatively with depression (HR 2.04, P optimism, anxiety or hopefulness. PFS was not associated with hope, optimism, anxiety or depression in any analyses. Depression and health utility, but not optimism, hope or anxiety, were associated with survival after controlling for known prognostic factors in patients with advanced colorectal cancer. Further research is required to understand the nature of the relationship between depression and survival. If a causal mechanism is identified, this may lead to interventional possibilities.

Gain of chromosome arm 1q in atypical meningioma correlates with shorter progression-free survival.

LENUS (Irish Health Repository)

2012-02-01

Aims: Atypical (WHO grade II) meningiomas have moderately high recurrence rates; even for completely resected tumours, approximately one-third will recur. Post-operative radiotherapy (RT) may aid local control and improve survival, but carries the risk of side effects. More accurate prediction of recurrence risk is therefore needed for patients with atypical meningioma. Previously, we used high-resolution array CGH to identify genetic variations in 47 primary atypical meningiomas and found that approximately 60% of tumors show gain of 1q at 1q25.1 and 1q25.3 to 1q32.1 and that 1q gain appeared to correlate with shorter progression-free survival. This study aimed to validate and extend these findings in an independent sample. Methods: 86 completely resected atypical meningiomas (with 25 recurrences) from two neurosurgical centres in Ireland were identified and clinical follow up was obtained. Utilizing a dual-colour interphase FISH assay, 1q gain was assessed using BAC probes directed against 1q25.1 and 1q32.1. Results: The results confirm the high prevalence of 1q gain at these loci in atypical meningiomas. We further show that gain at 1q32.1 and age each correlate with progression-free survival in patients who have undergone complete surgical resection of atypical meningiomas. Conclusions: These independent findings suggest that assessment of 1q copy number status can add clinically useful information for the management of patients with atypical meningiomas.

Irradiation of the potential cancer stem cell niches in the adult brain improves progression-free survival of patients with malignant glioma

International Nuclear Information System (INIS)

Evers, Patrick; Lee, Percy P; DeMarco, John; Agazaryan, Nzhde; Sayre, James W; Selch, Michael; Pajonk, Frank

2010-01-01

Glioblastoma is the most common brain tumor in adults. The mechanisms leading to glioblastoma are not well understood but animal studies support that inactivation of tumor suppressor genes in neural stem cells (NSC) is required and sufficient to induce glial cancers. This suggests that the NSC niches in the brain may harbor cancer stem cells (CSCs), Thus providing novel therapy targets. We hypothesize that higher radiation doses to these NSC niches improve patient survival by eradicating CSCs. 55 adult patients with Grade 3 or Grade 4 glial cancer treated with radiotherapy at UCLA between February of 2003 and May of 2009 were included in this retrospective study. Using radiation planning software and patient radiological records, the SVZ and SGL were reconstructed for each of these patients and dosimetry data for these structures was calculated. Using Kaplan-Meier analysis we show that patients whose bilateral subventricular zone (SVZ) received greater than the median SVZ dose (= 43 Gy) had a significant improvement in progression-free survival if compared to patients who received less than the median dose (15.0 vs 7.2 months PFS; P = 0.028). Furthermore, a mean dose >43 Gy to the bilateral SVZ yielded a hazard ratio of 0.73 (P = 0.019). Importantly, similarly analyzing total prescription dose failed to illustrate a statistically significant impact. Our study leads us to hypothesize that in glioma targeted radiotherapy of the stem cell niches in the adult brain could yield significant benefits over radiotherapy of the primary tumor mass alone and that damage caused by smaller fractions of radiation maybe less efficiently detected by the DNA repair mechanisms in CSCs

[Subgroup Analysis of the Non-interventional REASON Study: PFS and OS According to Age, Smoking History, Gender, and Histology in NSCLC Patients Treated with Gefitinib or Chemotherapy].

Science.gov (United States)

Schuette, W; Eberhardt, W E E; Waller, C; Schirmacher, P; Dietel, M; Zirrgiebel, U; Radke, S; Thomas, M

2016-09-01

Assessment of several clinical factors on progression-free (PFS) and overall survival (OS) in NSCLC patients (pts.) (stage IV) with mutated epidermal growth factor receptor (EGFRm+) treated with gefitinib (gef) or with chemotherapy (CT) under real-world conditions. 285 EGFRm+ pts. of the non-interventional REASON study treated with gef (n = 206) or CT (n = 79) as first-line therapy or with gef (n = 213) or CT (n = 61) in any line throughout the course of therapy were analyzed according to age, gender, smoking history and histology. Compared with CT, patients treated with gef showed prolongation of PFS and OS in all subgroups. PFS was significantly increased in women and non-smokers. OS was significantly increased in women, non-smokers, (ex)-smokers, patients with adenocarcinoma and elderly patients when treated with gef compared to CT. Female gender turned out to be an independent positive predictive factor for OS in patients treated with gef (HRmale: 1.74, p = 0.0009). A clinical benefit of gef was shown for all analyzed clinical subgroups of EGFRm+ pts. This was confirmed for the female gender in a multivariate analysis. © Georg Thieme Verlag KG Stuttgart · New York.

Phase II study of Gleevec® plus hydroxyurea (HU) in adults with progressive or recurrent meningioma.

Science.gov (United States)

Reardon, David A; Norden, Andrew D; Desjardins, Annick; Vredenburgh, James J; Herndon, James E; Coan, April; Sampson, John H; Gururangan, Sridharan; Peters, Katherine B; McLendon, Roger E; Norfleet, Julie A; Lipp, Eric S; Drappatz, Jan; Wen, Patrick Y; Friedman, Henry S

2012-01-01

We prospectively evaluated the efficacy and safety of imatinib plus hydroxyurea in patients with progressive/recurrent meningioma. A total of 21 patients with progressive/recurrent meningioma were enrolled in this dual center, single-arm, phase II trial. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 400 mg/day for patients not on CYP3A enzyme inducing anti-epileptic drugs (EIAEDs) and at 500 mg twice a day for patients on EIAEDs. The primary endpoint was progression-free survival at 6 months (PFS-6) and secondary endpoints were safety, radiographic response rate, and overall survival (OS). Best radiographic response was stable disease and was observed in 14 patients (67%). PFS-6 for all patients, those with grade I tumors (n = 8) and those with grade II or III tumors (n = 13) was 61.9, 87.5 and 46.2%, respectively. Patients with grade II or III tumors had poorer PFS and OS than those with grade I tumors, (P = 0.025 and P = 0.018) respectively. The only grade 3 or greater adverse event occurring in ≥ 10% of patients was anemia (10%). Imatinib plus hydroxyurea is well tolerated among patients with meningioma but has modest anti-tumor activity for this indication.

Increased tumour ADC value during chemotherapy predicts improved survival in unresectable pancreatic cancer

Energy Technology Data Exchange (ETDEWEB)

Nishiofuku, Hideyuki; Tanaka, Toshihiro; Kichikawa, Kimihiko [Nara Medical University, Department of Radiology and IVR Center, Kashihara-city, Nara (Japan); Marugami, Nagaaki [Nara Medical University, Department of Endoscopy and Ultrasound, Kashihara-city, Nara (Japan); Sho, Masayuki; Akahori, Takahiro; Nakajima, Yoshiyuki [Nara Medical University, Department of Surgery, Kashihara-city, Nara (Japan)

2016-06-15

To investigate whether changes to the apparent diffusion coefficient (ADC) of primary tumour in the early period after starting chemotherapy can predict progression-free survival (PFS) or overall survival (OS) in patients with unresectable pancreatic adenocarcinoma. Subjects comprised 43 patients with histologically confirmed unresectable pancreatic cancer treated with first-line chemotherapy. Minimum ADC values in primary tumour were measured using the selected area ADC (sADC), which excluded cystic and necrotic areas and vessels, and the whole tumour ADC (wADC), which included whole tumour components. Relative changes in ADC were calculated from baseline to 4 weeks after initiation of chemotherapy. Relationships between ADC and both PFS and OS were modelled by Cox proportional hazards regression. Median PFS and OS were 6.1 and 11.0 months, respectively. In multivariate analysis, sADC change was the strongest predictor of PFS (hazard ratio (HR), 4.5; 95 % confidence interval (CI), 1.7-11.9; p = 0.002). Multivariate Cox regression analysis for OS revealed sADC change and CRP as independent predictive markers, with sADC change as the strongest predictive biomarker (HR, 6.7; 95 % CI, 2.7-16.6; p = 0.001). Relative changes in sADC could provide a useful imaging biomarker to predict PFS and OS with chemotherapy for unresectable pancreatic adenocarcinoma. (orig.)

A retrospective analysis of survival and prognostic factors after stereotactic radiosurgery for aggressive meningiomas

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Ferraro, Daniel J; Zoberi, Imran; Simpson, Joseph R; Jaboin, Jerry J; Funk, Ryan K; Blackett, John William; Ju, Michelle R; DeWees, Todd A; Chicoine, Michael R; Dowling, Joshua L; Rich, Keith M; Drzymala, Robert E

2014-01-01

While most meningiomas are benign, aggressive meningiomas are associated with high levels of recurrence and mortality. A single institution’s Gamma Knife radiosurgical experience with atypical and malignant meningiomas is presented, stratified by the most recent WHO classification. Thirty-one patients with atypical and 4 patients with malignant meningiomas treated with Gamma Knife radiosurgery between July 2000 and July 2011 were retrospectively reviewed. All patients underwent prior surgical resection. Overall survival was the primary endpoint and rate of disease recurrence in the brain was a secondary endpoint. Patients who had previous radiotherapy or prior surgical resection were included. Kaplan-Meier and Cox proportional hazards models were used to estimate survival and identify factors predictive of recurrence and survival. Post-Gamma Knife recurrence was identified in 11 patients (31.4%) with a median overall survival of 36 months and progression-free survival of 25.8 months. Nine patients (25.7%) had died. Three-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 65.0%, respectively. WHO grade II 3-year OS and PFS were 83.4% and 70.1%, while WHO grade III 3-year OS and PFS were 33.3% and 0%. Recurrence rate was significantly higher in patients with a prior history of benign meningioma, nuclear atypia, high mitotic rate, spontaneous necrosis, and WHO grade III diagnosis on univariate analysis; only WHO grade III diagnosis was significant on multivariate analysis. Overall survival was adversely affected in patients with WHO grade III diagnosis, prior history of benign meningioma, prior fractionated radiotherapy, larger tumor volume, and higher isocenter number on univariate analysis; WHO grade III diagnosis and larger treated tumor volume were significant on multivariate analysis. Atypical and anaplastic meningiomas remain difficult tumors to treat. WHO grade III diagnosis and treated tumor volume were significantly

Survival End Points for Huntington Disease Trials Prior to a Motor Diagnosis.

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Long, Jeffrey D; Mills, James A; Leavitt, Blair R; Durr, Alexandra; Roos, Raymund A; Stout, Julie C; Reilmann, Ralf; Landwehrmeyer, Bernhard; Gregory, Sarah; Scahill, Rachael I; Langbehn, Douglas R; Tabrizi, Sarah J

2017-11-01

Predictive genetic testing in Huntington disease (HD) enables therapeutic trials in HTT gene expansion mutation carriers prior to a motor diagnosis. Progression-free survival (PFS) is the composite of a motor diagnosis or a progression event, whichever comes first. To determine if PFS provides feasible sample sizes for trials with mutation carriers who have not yet received a motor diagnosis. This study uses data from the 2-phase, longitudinal cohort studies called Track and from a longitudinal cohort study called the Cooperative Huntington Observational Research Trial (COHORT). Track had 167 prediagnosis mutation carriers and 156 noncarriers, whereas COHORT had 366 prediagnosis mutation carriers and noncarriers. Track studies were conducted at 4 sites in 4 countries (Canada, France, England, and the Netherlands) from which data were collected from January 17, 2008, through November 17, 2014. The COHORT was conducted at 38 sites in 3 countries (Australia, Canada, and the United States) from which data were collected from February 14, 2006, through December 31, 2009. Results from the Track data were externally validated with data from the COHORT. The required sample size was estimated for a 2-arm prediagnosis clinical trial. Data analysis took place from May 1, 2016, to June 10, 2017. The primary end point is PFS. Huntington disease progression events are defined for the Unified Huntington's Disease Rating Scale total motor score, total functional capacity, symbol digit modalities test, and Stroop word test. Of Track's 167 prediagnosis mutation carriers, 93 (55.6%) were women, and the mean (SD) age was 40.06 (8.92) years; of the 156 noncarriers, 87 (55.7%) were women, and the mean (SD) age was 45.58 (10.30) years. Of the 366 COHORT participants, 229 (62.5%) were women and the mean (SD) age was 42.21 (12.48) years. The PFS curves of the Track mutation carriers showed good external validity with the COHORT mutation carriers after adjusting for initial progression. For

Overexpression of Insulin-like Growth Factor-1 Receptor Is Associated With Penile Cancer Progression.

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Ball, Mark W; Bezerra, Stephania M; Chaux, Alcides; Faraj, Sheila F; Gonzalez-Roibon, Nilda; Munari, Enrico; Sharma, Rajni; Bivalacqua, Trinity J; Netto, George J; Burnett, Arthur L

2016-06-01

To evaluate insulin-like growth factor-1 receptor (IGF1R) expression in penile cancer and its association with oncologic outcomes. Tissue microarrays were constructed from 53 patients treated at our institution. Expression of IGF1R was evaluated using a Her2-like scoring system. Overexpression was defined as 1+ or greater membranous staining. Association of IGF1R expression with pathologic features was assessed with comparative statistics, and association with local recurrence, progression to nodal or distance metastases, or death was assessed with Kaplan-Meier survival analysis and Cox proportional hazard regression models. Overall, IGF1R overexpression was seen in 33 (62%) cases. With a median follow-up of 27.8 months, IGF1R overexpression was associated with inferior progression-free survival (PFS) (P  =  .003). In a multivariable model controlling for grade, T stage, perineural invasion, and lymphovascular invasion, IGF1R expression was independently associated with disease progression (hazard ratio 2.3, 95% confidence interval 1.1-5.1, P  =  .03. Comparing patients without IGF1R overexpression to those with overexpression, 5-year PFS was 94.1% vs 45.8%. IGF1R overexpression was associated with inferior PFS in penile cancer. Drugs that target IGF1R and downstream messengers may have a therapeutic benefit in patients that exhibit IGF1R overexpression. Copyright © 2016 Elsevier Inc. All rights reserved.

[Exon-dependent Subgroup-analysis of the Non-interventional REASON-Study: PFS and OS in EGFR-mutated NSCLC Patients Treated with Gefitinib or Chemotherapy].

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Schuette, W; Dietel, M; Thomas, M; Eberhardt, W; Griesinger, F; Zirrgiebel, U; Radke, S; Schirmacher, P

2016-08-01

To analyze the influence of the localization of mutations in the epidermal growth factor receptor (EGFR) gene on progression-free (PFS) and overall survival (OS) in patients (pts) with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with gefitinib (gef) or chemotherapy (CT) under real world conditions within the REASON study. Subgroups of pts with mutations in exon 19 (n = 141), 18/20 (n = 43), and 21 (n = 104) were analyzed for PFS and OS according to gef or CT treatment and compared using the log-rank test. Pts with mutations in exon 19 and 18/20 treated with gef as first line therapy showed increased PFS and OS compared to CT. This increase was statistically significant in pts with exon 19 mutation (11.3 vs. 6.5 months), but was not found in pts with exon 21 mutation (9.1 vs. 9.3 months). Also, OS was significantly increased in patients with mutation in exon 19 treated with gef ever over all treatment lines compared to CT (21.8 vs. 10.6 months), whereas this was not found in pts with mutation in exon 21 (14.1 vs. 13.9 months). Localization and nature of EGFR mutations influences gefitinib treatment outcomes under routine conditions and should therefore be analyzed in detail. © Georg Thieme Verlag KG Stuttgart · New York.

Metronomic Chemotherapy vs Best Supportive Care in Progressive Pediatric Solid Malignant Tumors: A Randomized Clinical Trial.

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Pramanik, Raja; Agarwala, Sandeep; Gupta, Yogendra Kumar; Thulkar, Sanjay; Vishnubhatla, Sreenivas; Batra, Atul; Dhawan, Deepa; Bakhshi, Sameer

2017-09-01

Although oral metronomic chemotherapy is often used in progressive pediatric solid malignant tumors, a literature review reveals that only small single-arm retrospective or phase 1 and 2 studies have been performed. Skepticism abounds because of the lack of level 1 evidence. To compare the effect of metronomic chemotherapy on progression-free survival (PFS) with that of placebo in pediatric patients with primary extracranial, nonhematopoietic solid malignant tumors that progress after at least 2 lines of chemotherapy. A double-blinded, placebo-controlled randomized clinical trial was conducted from October 1, 2013, through December 31, 2015, at the cancer center at All India Institute of Medical Sciences in children aged 5 to 18 years with primary extracranial, nonhematopoietic solid malignant tumors that progressed after at least 2 lines of chemotherapy and had no further curative options. One arm received a 4-drug oral metronomic regimen of daily celecoxib and thalidomide with alternating periods of etoposide and cyclophosphamide, whereas the other arm received placebo. Disease status was assessed at baseline, 9 weeks, 18 weeks, and 27 weeks or at clinical progression. The primary end point was PFS as defined by the proportion of patients without disease progression at 6 months, and PFS duration and overall survival (OS) were secondary end points. A total of 108 of the 123 patients screened were enrolled, with 52 randomized to the placebo group (median age, 15 years; 40 male [76.9%]) and 56 to the metronomic chemotherapy group (median age, 13 years; 42 male [75.0%]). At a median follow-up of 2.9 months, 100% of the patients had disease progression by 6 months in the placebo group vs 96.4% in the metronomic chemotherapy group (P = .24). Median PFS and OS in the 2 groups was similar (hazard ratio [HR], 0.69; 95% CI, 0.47-1.03 [P = .07] for PFS; and HR, 0.74; 95% CI, 0.50-1.09 [P = .13] for OS). In post hoc subgroup analysis, cohorts receiving more than

A Case Series of Survival Outcomes in Patients with Advanced-stage IIIb/IV Non-small-cell Lung Cancer Treated with HangAm-Plus

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Bang Sun-Hwi

2012-06-01

Full Text Available Background and Objectives: Non-small-cell lung cancer (NSCLC represents approximately 80% of all lung cancers. Unfortunately, at their time of diagnosis, most patients have advanced to unresectable disease with a very poor prognosis. The oriental herbal medicine HangAm-Plus (HAP has been developed for antitumor purposes, and several previous studies have reported its therapeutic effects. In this study, the efficacy of HAP was evaluated as a third-line treatment for advanced-stage IIIb/IV NSCLC. Methods: The study involved six patients treated at the East- West Cancer Center (EWCC from April 2010 to October 2011. Inoperable advanced-stage IIIb/IV NSCLC patients received 3,000 or 6,000 mg of HAP on a daily basis over a 12-week period. Computed tomography (CT scans were obtained from the patients at the time of the initial administration and after 12 weeks of treatment. We observed and analyzed the patients overall survival (OS and progression-free survival (PFS. Results: Of the six patients, three expired during the study, and the three remaining patients were alive as of October 31, 2011. The OS ranged from 234 to 512 days, with a median survival of 397 days and a one-year survival rate of 66.7%. In the 12-week-interval chest CT assessment, three patients showed stable disease (SD, and the other three showed progressive disease (PD. The PFS of patients ranged from 88 to 512 days, the median PFS being 96 days. Longer OS and PFS were correlated with SD. Although not directly comparable, the OS and the PFS of this study were greater than those of the docetaxel or the best supportive care group in other studies. Conclusion: HAP may prolong the OS and the PFS of inoperable stage IIIb/IV NSCLC patients without significant adverse effects. In the future, more controlled clinical trials with larger samples from multi-centers should be conducted to evaluate the efficacy and the safety of HAP.

SU-F-R-04: Radiomics for Survival Prediction in Glioblastoma (GBM)

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Zhang, H; Molitoris, J; Bhooshan, N; Choi, W; Lu, W; Mehta, M; D’Souza, W [University of Maryland School of Medicine, Baltimore, MD (United States); Tan, S [Huazhong University of Science & Technology, Wuhan (China); Giacomelli, I; Scartoni, D [University of Florence, Florence (Italy); Gzell, C [Northern Sydney Cancer Centre, Sydney (Australia)

2016-06-15

Purpose: To develop a quantitative radiomics approach for survival prediction of glioblastoma (GBM) patients treated with chemoradiotherapy (CRT). Methods: 28 GBM patients who received CRT at our institution were retrospectively studied. 255 radiomic features were extracted from 3 gadolinium-enhanced T1 weighted MRIs for 2 regions of interest (ROIs) (the surgical cavity and its surrounding enhancement rim). The 3 MRIs were at pre-treatment, 1-month and 3-month post-CRT. The imaging features comprehensively quantified the intensity, spatial variation (texture), geometric property and their spatial-temporal changes for the 2 ROIs. 3 demographics features (age, race, gender) and 12 clinical parameters (KPS, extent of resection, whether concurrent temozolomide was adjusted/stopped and radiotherapy related information) were also included. 4 Machine learning models (logistic regression (LR), support vector machine (SVM), decision tree (DT), neural network (NN)) were applied to predict overall survival (OS) and progression-free survival (PFS). The number of cases and percentage of cases predicted correctly were collected and AUC (area under the receiver operating characteristic (ROC) curve) were determined after leave-one-out cross-validation. Results: From univariate analysis, 27 features (1 demographic, 1 clinical and 25 imaging) were statistically significant (p<0.05) for both OS and PFS. Two sets of features (each contained 24 features) were algorithmically selected from all features to predict OS and PFS. High prediction accuracy of OS was achieved by using NN (96%, 27 of 28 cases were correctly predicted, AUC = 0.99), LR (93%, 26 of 28 cases were correctly predicted, AUC = 0.95) and SVM (93%, 26 of 28 cases were correctly predicted, AUC = 0.90). When predicting PFS, NN obtained the highest prediction accuracy (89%, 25 of 28 cases were correctly predicted, AUC = 0.92). Conclusion: Radiomics approach combined with patients’ demographics and clinical parameters can

Enhancing tumor apparent diffusion coefficient histogram skewness stratifies the postoperative survival in recurrent glioblastoma multiforme patients undergoing salvage surgery.

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Zolal, Amir; Juratli, Tareq A; Linn, Jennifer; Podlesek, Dino; Sitoci Ficici, Kerim Hakan; Kitzler, Hagen H; Schackert, Gabriele; Sobottka, Stephan B; Rieger, Bernhard; Krex, Dietmar

2016-05-01

Objective To determine the value of apparent diffusion coefficient (ADC) histogram parameters for the prediction of individual survival in patients undergoing surgery for recurrent glioblastoma (GBM) in a retrospective cohort study. Methods Thirty-one patients who underwent surgery for first recurrence of a known GBM between 2008 and 2012 were included. The following parameters were collected: age, sex, enhancing tumor size, mean ADC, median ADC, ADC skewness, ADC kurtosis and fifth percentile of the ADC histogram, initial progression free survival (PFS), extent of second resection and further adjuvant treatment. The association of these parameters with survival and PFS after second surgery was analyzed using log-rank test and Cox regression. Results Using log-rank test, ADC histogram skewness of the enhancing tumor was significantly associated with both survival (p = 0.001) and PFS after second surgery (p = 0.005). Further parameters associated with prolonged survival after second surgery were: gross total resection at second surgery (p = 0.026), tumor size (0.040) and third surgery (p = 0.003). In the multivariate Cox analysis, ADC histogram skewness was shown to be an independent prognostic factor for survival after second surgery. Conclusion ADC histogram skewness of the enhancing lesion, enhancing lesion size, third surgery, as well as gross total resection have been shown to be associated with survival following the second surgery. ADC histogram skewness was an independent prognostic factor for survival in the multivariate analysis.

Smoking may modify the association between neoadjuvant chemotherapy and survival from ovarian cancer.

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Kelemen, Linda E; Warren, Graham W; Koziak, Jennifer M; Köbel, Martin; Steed, Helen

2016-01-01

Tobacco smoking by cancer patients is associated with increased mortality. Less is known of the impact of smoking on recurrence risk and interaction with chemotherapy treatment. We examined these associations in ovarian cancer. Patients were identified from the Alberta Cancer Registry between 1978 and 2010 and were oversampled for less-common histologic ovarian tumor types. Medical records were abstracted for 678 eligible patients on lifestyle, medical and cancer treatment, and review of pathology slides was performed for 605 patients. We estimated hazard ratios (HR) and 95% confidence intervals (CI) using Cox proportional hazard models adjusted for age at diagnosis, race, stage and residual disease. Among patients receiving adjuvant chemotherapy (N=432), current smoking was significantly associated with shorter duration of overall (OS; HR, 8.56; 95% CI, 1.50-48.7) and progression-free (PFS; HR, 5.74; 95% CI, 1.05-31.4) survival from mucinous ovarian cancer only. There was no significant association between neoadjuvant chemotherapy and survival. However, among patients receiving neoadjuvant chemotherapy (N=44), current smokers had shorter PFS (HR, 4.32; 95% CI, 1.36-13.8; N=32 progressed/9 censored events) compared to never smokers, but the HRs were not statistically different across smoking categories (P interaction=0.87). Adverse associations were observed between smoking status and OS or PFS among patients with mucinous ovarian cancer receiving adjuvant chemotherapy. No significant effect was found from neoadjuvant chemotherapy on PFS overall; however, smoking may modify this association. Although needing replication, these findings suggest that patients may benefit from smoking cessation interventions prior to treatment with chemotherapy. Copyright © 2015 Elsevier Inc. All rights reserved.

Androgen Deprivation Therapy Does Not Impact Cause-Specific or Overall Survival in High-Risk Prostate Cancer Managed With Brachytherapy and Supplemental External Beam

International Nuclear Information System (INIS)

Merrick, Gregory S.; Butler, Wayne M.; Wallner, Kent E.; Galbreath, Robert W.; Allen, Zachariah A.; Adamovich, Edward; Lief, Jonathan

2007-01-01

Purpose: To determine cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) in high-risk prostate cancer patients undergoing brachytherapy with or without supplemental therapies. Methods and Materials: Between April 1995 and July 2002, 204 patients with high-risk prostate cancer (Gleason score ≥8 or prostate-specific antigen [PSA] >20 ng/mL or clinical stage ≥T2c) underwent brachytherapy. Median follow-up was 7.0 years. The bPFS was defined by a PSA ≤0.40 ng/mL after nadir. Multiple clinical, treatment, and dosimetric parameters were evaluated for the impact on survival. Results: The 10-year CSS, bPFS, and OS were 88.9%, 86.6%, and 68.6%, respectively. A statistically significant difference in bPFS was discerned between hormone naive, ADT ≤6 months, and ADT >6 month cohorts (79.7% vs. 95.% vs. 89.9%, p = 0.032). Androgen deprivation therapy (ADT) did not impact CSS or OS. For bPFS patients, the median posttreatment PSA was <0.04 ng/mL. A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS, whereas percent positive biopsies and duration of ADT best predicted for bPFS. The OS was best predicted by Gleason score and diabetes. Thirty-eight patients have died, with 26 of the deaths from cardiovascular/pulmonary disease or second malignancy. Eleven patients have died of metastatic prostate cancer. Conclusions: The ADT improved 10-year bPFS without statistical impact on CSS or OS. Death as a result of cardiovascular/pulmonary disease and second malignancies were more than twice as common as prostate cancer deaths. Strategies to improve cardiovascular health should positively impact OS

Outcome predictors in the management of intramedullary classic ependymoma: An integrative survival analysis.

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Wang, Yinqing; Cai, Ranze; Wang, Rui; Wang, Chunhua; Chen, Chunmei

2018-06-01

This is a retrospective study.The aim of this study was to illustrate the survival outcomes of patients with classic ependymoma (CE) and identify potential prognostic factors.CE is the most common category of spinal ependymomas, but few published studies have discussed predictors of the survival outcome.A Boolean search of the PubMed, Embase, and OVID databases was conducted by 2 investigators independently. The objects were intramedullary grade II ependymoma according to 2007 WHO classification. Univariate Kaplan-Meier analysis and Log-Rank tests were performed to identify variables associated with progression-free survival (PFS) or overall survival (OS). Multivariate Cox regression was performed to assess hazard ratios (HRs) with 95% confidence intervals (95% CIs). Statistical analysis was performed by SPSS version 23.0 (IBM Corp.) with statistical significance defined as P analysis showed that patients who had undergone total resection (TR) had better PFS and OS than those with subtotal resection (STR) and biopsy (P = .002, P = .004, respectively). Within either univariate or multivariate analysis (P = .000, P = .07, respectively), histological type was an independent prognostic factor for PFS of CE [papillary type: HR 0.002, 95% CI (0.000-0.073), P = .001, tanycytic type: HR 0.010, 95% CI (0.000-0.218), P = .003].It was the first integrative analysis of CE to elucidate the correlation between kinds of factors and prognostic outcomes. Definite histological type and safely TR were foundation of CE's management. 4.

Plasma miR-200b in ovarian carcinoma patients: distinct pattern of pre/post-treatment variation compared to CA-125 and potential for prediction of progression-free survival.

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Kapetanakis, Nikiforos-Ioannis; Uzan, Catherine; Jimenez-Pailhes, Anne-Sophie; Gouy, Sébastien; Bentivegna, Enrica; Morice, Philippe; Caron, Olivier; Gourzones-Dmitriev, Claire; Le Teuff, Gwénaël; Busson, Pierre

2015-11-03

Ovarian carcinomas (OvCa) are highly heterogeneous malignancies. We investigated four circulating plasma microRNAs (miR-21, miR-34a, miR-200b and miR-205) as candidate biomarkers. Using qPCR, we assessed the plasma concentration of these markers in 101 women, including 51 previously untreated OvCa patients, 25 healthy women and 25 patients bearing benign pelvic lesions. For a subset of 33 OvCa patients, the assay was repeated at the end of the primary treatment. The pattern of variations (post- minus pre-treatment) of concentration was compared to that of CA-125. A Cox regression model was used to study the association between variations and the progression-free survival (PFS). Plasma miR-200b proved to have a greater average concentration in OvCa samples (median 2-ΔΔCt = 15.18) than in samples linked to non-malignant lesions (median 2-ΔΔCt = 1.26, p-value = 0.0004). Its concentration was highly heterogeneous among OvCa patients, without any correlations with the FIGO stage and the pre-treatment CA-125 level. The decrease in CA-125 concentration was constant and often dramatic, while the variations of miR-200b concentration were much more diverse. The variation of miR-200b was marginally associated with the PFS (hazard ratio=2.95 95%CI=[0.94; 9.28], p=0.06) while miR-200b as a continuous time-dependent variable was significantly associated (HR=1.06 [1.02; 1.10], p=0.003). This study is the first direct empirical evidence that miR-200b can provide additional information, independent of CA-125 in OvCa patients.

P02.03INCREASED COUNTS OF NK AND NKT CELLS ARE ASSOCIATED WITH PROLONGED SURVIVAL IN PRIMARY GLIOBLASTOMA PATIENTS TREATED WITH DENDRITIC CELL IMMUNOTHERAPY IN COMBINATION WITH RADIO- AND CHEMO-THERAPY

Science.gov (United States)

Pellegatta, S.; Eoli, M.; Cantini, G.; Anghileri, E.; Antozzi, C.; Frigerio, S.; Bruzzone, M.; Pollo, B.; Parati, E.; Finocchiaro, G.

2014-01-01

Two clinical studies, DENDR1 and DENDR2 including, respectively, the treatment of first diagnosis and recurrent glioblastoma (GB) patients with dendritic cells (DCs) loaded with autologous tumor lysate are currently active at Istituto Neurologico Besta, Milan. Our first results obtained on a group of recurrent GB patients demonstrated that the response of NK cells correlates with significantly prolonged survival. Here we provide results of the interim analysis on 22 patients affected by primary GB. Patients with post-surgery volume ≤10 cc underwent leukapheresis before radiotherapy and chemotherapy with temozolomide (TMZ). Three intradermal injections of mature DC were done before adjuvant chemotherapy. The subsequent 4 injections were performed 17 ± 3 days after adjuvant TMZ. MRI, clinical and immunological follow-up were performed every 2 months. The median age at surgery was 54.5 years (28-69). RT-TMZ induced significant lymphopenia (1000 lymphocytes/microl (5/22) before first vaccination had shorter PFS than others (p < 0.005). Peripheral Blood Lymphocytes (PBLs) were analyzed by flow cytometry to identify CD8+ T cells, NK and NKT cells before and after DC vaccines. The ratio of vaccination/baseline frequencies and counts (V/B ratio) of all of the immunological parameters for each patient was calculated, and the median of all of the observations used as the cut off value to separate patients. V/B ratio was correlated with the progression free survival (PFS) of each patient. Increased V/B ratio for NK cells and in particular NKT cells, but not for CD8 T lymphocytes, was significantly associated with prolonged PFS (median PFS 14 vs 8.0 mo, p = 0.01; 15.0 vs 8.0 mo, respectively). Interferon (IFN)-γ in PBLs was significantly higher in patients with PFS12 (p < 0.02), increasing immediately after the second vaccination as evaluated by real time-PCR. No changes in the expression levels of IFN-γ were observed in the other patients. After a median follow up of 14

Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery.

Science.gov (United States)

Matsuo, Koji; Johnson, Marian S; Im, Dwight D; Ross, Malcolm S; Bush, Stephen H; Yunokawa, Mayu; Blake, Erin A; Takano, Tadao; Klobocista, Merieme M; Hasegawa, Kosei; Ueda, Yutaka; Shida, Masako; Baba, Tsukasa; Satoh, Shinya; Yokoyama, Takuhei; Machida, Hiroko; Ikeda, Yuji; Adachi, Sosuke; Miyake, Takahito M; Iwasaki, Keita; Yanai, Shiori; Takeuchi, Satoshi; Nishimura, Masato; Nagano, Tadayoshi; Takekuma, Munetaka; Shahzad, Mian M K; Pejovic, Tanja; Omatsu, Kohei; Kelley, Joseph L; Ueland, Frederick R; Roman, Lynda D

2018-03-01

To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy. This is a nested case-control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival (CSS) were examined. The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery. © 2017 Wiley Periodicals, Inc.

Development of anti-drug antibodies is associated with shortened survival in patients with metastatic melanoma treated with ipilimumab

DEFF Research Database (Denmark)

Kverneland, Anders H.; Enevold, Christian; Donia, Marco

2018-01-01

significantly with a shorter OS (p = 0.01) and PFS (p = 0.02). Eight patients (26%) were ADA-positive at either timepoint. ADA positivity correlated significantly with a shorter OS (p = 0.03) with a hazard ratio (HR) of 3.0 (95% CI: 1.2-7.8). Four of 8 ADA-positive patients (50%) discontinued therapy before......Introduction: Checkpoint inhibitors, including the CTLA-4 blocking antibody ipilimumab, have become the new standard therapy for many metastatic cancers. Development of anti-drug antibodies (ADAs) after treatment with other biopharmaceuticals has been thoroughly described, but the induction of ADAs...... for serum levels of ipilimumab and ADAs to ipilimumab at baseline, and before the 2nd and 4th infusion using an in-house bead-based assay. The results were correlated with progression-free survival (PFS) and overall survival (OS). Results: Low serum levels of ipilimumab before the 2nd infusion correlated...

HE4 as a predictor of adjuvant chemotherapy resistance and survival in patients with epithelial ovarian cancer

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Aarenstrup Karlsen, Mona; Høgdall, Claus; Nedergaard, Lotte

2016-01-01

The aim of this study was to investigate the value of serum human epididymis protein 4 (HE4) and HE4 tissue protein expression to predict tumor resistance to adjuvant chemotherapy, progression-free survival (PFS), and overall survival in patients with epithelial ovarian cancer (EOC). Consecutive...... inclusion of 198 patients diagnosed with EOC was conducted. Blood samples were collected prior to surgery and tissue samples during surgery. Patient data were registered prospectively in the Danish Gynecologic Cancer Database. The association between serum HE4 and HE4 tissue protein expression, resistance...... significantly (p tissue protein expression...

Association between time to disease progression end points and overall survival in patients with neuroendocrine tumors

Directory of Open Access Journals (Sweden)

Singh S

2014-08-01

Full Text Available Simron Singh,1 Xufang Wang,2 Calvin HL Law1 1Sunnybrook Odette Cancer Center, University of Toronto, Toronto, ON, Canada; 2Novartis Oncology, Florham Park, NJ, USA Abstract: Overall survival can be difficult to determine for slowly progressing malignancies, such as neuroendocrine tumors. We investigated whether time to disease progression is positively associated with overall survival in patients with such tumors. A literature review identified 22 clinical trials in patients with neuroendocrine tumors that reported survival probabilities for both time to disease progression (progression-free survival and time to progression and overall survival. Associations between median time to disease progression and median overall survival and between treatment effects on time to disease progression and treatment effects on overall survival were analyzed using weighted least-squares regression. Median time to disease progression was significantly associated with median overall survival (coefficient 0.595; P=0.022. In the seven randomized studies identified, the risk reduction for time to disease progression was positively associated with the risk reduction for overall survival (coefficient on −ln[HR] 0.151; 95% confidence interval −0.843, 1.145; P=0.713. The significant association between median time to disease progression and median overall survival supports the assertion that time to disease progression is an alternative end point to overall survival in patients with neuroendocrine tumors. An apparent albeit not significant trend correlates treatment effects on time to disease progression and treatment effects on overall survival. Informal surveys of physicians’ perceptions are consistent with these concepts, although additional randomized trials are needed. Keywords: neuroendocrine tumors, progression-free survival, disease progression, mortality

Optimisation of chemotherapy and radiotherapy for untreated Hodgkin lymphoma patients with respect to second malignant neoplasms, overall and progression-free survival: individual participant data analysis.

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Franklin, Jeremy; Eichenauer, Dennis A; Becker, Ingrid; Monsef, Ina; Engert, Andreas

2017-09-13

Efficacy and the risk of severe late effects have to be well-balanced in treatment of Hodgkin lymphoma (HL). Late adverse effects include secondary malignancies which often have a poor prognosis. To synthesise evidence on the risk of secondary malignancies after current treatment approaches comprising chemotherapy and/or radiotherapy, we performed a meta-analysis based on individual patient data (IPD) from patients treated for newly diagnosed HL. We investigated several questions concerning possible changes in the risk of secondary malignancies when modifying chemotherapy or radiotherapy (omission of radiotherapy, reduction of the radiation field, reduction of the radiation dose, use of fewer chemotherapy cycles, intensification of chemotherapy). We also analysed whether these modifications affect progression-free survival (PFS) and overall survival (OS). We searched MEDLINE and Cochrane CENTRAL trials databases comprehensively in June 2010 for all randomised trials in HL since 1984. Key international trials registries were also searched. The search was updated in March 2015 without collecting further IPD (one further eligible study found) and again in July 2017 (no further eligible studies). We included randomised controlled trials (RCTs) for untreated HL patients which enrolled at least 50 patients per arm, completed recruitment by 2007 and performed a treatment comparison relevant to our objectives. Study groups submitted IPD, including age, sex, stage and the outcomes secondary malignant neoplasm (SMN), OS and PFS as time-to-event data. We meta-analysed these data using Petos method (SMN) and Cox regression with inverse-variance pooling (OS, PFS) for each of the five study questions, and performed subgroup and sensitivity analyses to assess the applicability and robustness of the results. We identified 21 eligible trials and obtained IPD for 16. For four studies no data were supplied despite repeated efforts, while one study was only identified in 2015 and IPD

Multicentre phase II studies evaluating imatinib plus hydroxyurea in patients with progressive glioblastoma.

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Reardon, D A; Dresemann, G; Taillibert, S; Campone, M; van den Bent, M; Clement, P; Blomquist, E; Gordower, L; Schultz, H; Raizer, J; Hau, P; Easaw, J; Gil, M; Tonn, J; Gijtenbeek, A; Schlegel, U; Bergstrom, P; Green, S; Weir, A; Nikolova, Z

2009-12-15

We evaluated the efficacy of imatinib mesylate in addition to hydroxyurea in patients with recurrent glioblastoma (GBM) who were either on or not on enzyme-inducing anti-epileptic drugs (EIAEDs). A total of 231 patients with GBM at first recurrence from 21 institutions in 10 countries were enrolled. All patients received 500 mg of hydroxyurea twice a day. Imatinib was administered at 600 mg per day for patients not on EIAEDs and at 500 mg twice a day if on EIAEDs. The primary end point was radiographic response rate and secondary end points were safety, progression-free survival at 6 months (PFS-6), and overall survival (OS). The radiographic response rate after centralised review was 3.4%. Progression-free survival at 6 months and median OS were 10.6% and 26.0 weeks, respectively. Outcome did not appear to differ based on EIAED status. The most common grade 3 or greater adverse events were fatigue (7%), neutropaenia (7%), and thrombocytopaenia (7%). Imatinib in addition to hydroxyurea was well tolerated among patients with recurrent GBM but did not show clinically meaningful anti-tumour activity.

10-Year Survival and Quality of Life in Patients With High-Risk PN0 Prostate Cancer Following Definitive Radiotherapy

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Berg, Arne; Lilleby, Wolfgang; Bruland, Oyvind Sverre; Fossa, Sophie Dorothea

2007-01-01

Purpose: To evaluate long-term overall survival (OS), cancer-specific survival (CSS), clinical progression-free survival (cPFS), and health-related quality of life (HRQoL) following definitive radiotherapy (RT) given to T 1-4p N 0 M 0 prostate cancer patients provided by a single institution between 1989 and 1996. Methods and Materials: We assessed outcome among 203 patients who had completed three-dimensional conformal RT (66 Gy) without hormone treatment and in whom staging by lymphadenectomy had been performed. OS was compared with an age-matched control group from the general population. A cross-sectional, self-report survey of HRQoL was performed among surviving patients. Results: Median observation time was 10 years (range, 1-16 years). Eighty-one percent had high-risk tumors defined as T 3-4 or Gleason score (GS) ≥7B (4+3). Among these, 10-year OS, CSS, and cPFS rates were 52%, 66%, and 39%, respectively. The corresponding fractions in low-risk patients (T 1-2 and GS ≤7A [3+4]) were 79%, 95%, and 73%, respectively. Both CSS and cPFS were predicted by GS and T-classification; OS was associated with GS only. High-risk, but not low-risk, patients had reduced OS compared with the general population (p p N 0 , RT with dosage 3-4 or GS ≥7B

Decitabine improves progression-free survival in older high-risk MDS patients with multiple autosomal monosomies: results of a subgroup analysis of the randomized phase III study 06011 of the EORTC Leukemia Cooperative Group and German MDS Study Group.

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Lübbert, Michael; Suciu, Stefan; Hagemeijer, Anne; Rüter, Björn; Platzbecker, Uwe; Giagounidis, Aristoteles; Selleslag, Dominik; Labar, Boris; Germing, Ulrich; Salih, Helmut R; Muus, Petra; Pflüger, Karl-Heinz; Schaefer, Hans-Eckart; Bogatyreva, Lioudmila; Aul, Carlo; de Witte, Theo; Ganser, Arnold; Becker, Heiko; Huls, Gerwin; van der Helm, Lieke; Vellenga, Edo; Baron, Frédéric; Marie, Jean-Pierre; Wijermans, Pierre W

2016-01-01

In a study of elderly AML patients treated with the hypomethylating agent decitabine (DAC), we noted a surprisingly favorable outcome in the (usually very unfavorable) subgroup with two or more autosomal monosomies (MK2+) within a complex karyotype (Lübbert et al., Haematologica 97:393-401, 2012). We now analyzed 206 myelodysplastic syndrome (MDS) patients (88 % of 233 patients randomized in the EORTC/GMDSSG phase III trial 06011, 61 of them with RAEBt, i.e. AML by WHO) with cytogenetics informative for MK status.. Endpoints are the following: complete/partial (CR/PR) and overall response rate (ORR) and progression-free (PFS) and overall survival (OS). Cytogenetic subgroups are the following: 63 cytogenetically normal (CN) patients, 143 with cytogenetic abnormalities, 73 of them MK-negative (MK-), and 70 MK-positive (MK+). These MK+ patients could be divided into 17 with a single autosomal monosomy (MK1) and 53 with at least two monosomies (MK2+). ORR with DAC in CN patients: 36.1 %, in MK- patients: 16.7 %, in MK+ patients: 43.6 % (MK1: 44.4 %, MK2+ 43.3 %). PFS was prolonged by DAC compared to best supportive care (BSC) in the CN (hazard ratio (HR) 0.55, 99 % confidence interval (CI), 0.26; 1.15, p = 0.03) and MK2+ (HR 0.50; 99 % CI, 0.23; 1.06, p = 0.016) but not in the MK-, MK+, and MK1 subgroups. OS was not improved by DAC in any subgroup. In conclusion, we demonstrate for the first time in a randomized phase III trial that high-risk MDS patients with complex karyotypes harboring two or more autosomal monosomies attain encouraging responses and have improved PFS with DAC treatment compared to BSC.

The Role of the Neutrophil to Lymphocyte Ratio for Survival Outcomes in Patients with Metastatic Castration-Resistant Prostate Cancer Treated with Abiraterone

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Martin Boegemann

2017-02-01

Full Text Available The purpose of this study was to examine the prognostic capability of baseline neutrophil-to-lymphocyte-ratio (NLR and NLR-change under Abiraterone in metastatic castration-resistant prostate cancer patients. The impact of baseline NLR and change after eight weeks of treatment on progression-free survival (PFS and overall survival (OS was analyzed using Kaplan-Meier-estimates and Cox-regression. 79 men with baseline NLR <5 and 17 with NLR >5 were analyzed. In baseline analysis of PFS NLR >5 was associated with non-significantly shorter median PFS (five versus 10 months (HR: 1.6 (95%CI:0.9–2.8; p = 0.11. After multivariate adjustment (MVA, ECOG > 0–1, baseline LDH>upper limit of normal (UNL and presence of visceral metastases were independent prognosticators. For OS, NLR >5 was associated with shorter survival (seven versus 19 months (HR: 2.3 (95%CI:1.3–4.0; p < 0.01. In MVA, ECOG > 0–1 and baseline LDH > UNL remained independent prognosticators. After 8 weeks of Abiraterone NLR-change to <5 prognosticated worse PFS (five versus 12 months (HR: 4.1 (95%CI:1.1–15.8; p = 0.04. MVA showed a trend towards worse PFS for NLR-change to <5 (p = 0.11. NLR-change to <5 led to non-significant shorter median OS (seven versus 16 months (HR: 2.3 (95%CI:0.7–7.1; p = 0.15. MVA showed non-significant difference for OS. We concluded baseline NLR <5 is associated with improved survival. In contrast, in patients with baseline NLR >5, NLR-change to <5 after eight weeks of Abiraterone was associated with worse survival and should be interpreted carefully.

Valproic acid reduces hair loss and improves survival in patients receiving temozolomide-based radiation therapy for high-grade glioma.

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Watanabe, Shinichi; Kuwabara, Yui; Suehiro, Satoshi; Yamashita, Daisuke; Tanaka, Mamoru; Tanaka, Akihiro; Ohue, Shiro; Araki, Hiroaki

2017-03-01

Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is also used to manage seizures in glioblastoma patients. HDAC inhibitors can protect normal cells and tissues from the deleterious effects of radiotherapy, and VPA is reported to improve the survival of glioblastoma patients receiving chemoradiation therapy. VPA also promotes hair growth, and thus has the potential to reduce the radiotherapy side effect of hair loss while improving the survival of patients with glioblastoma. The purpose of this study was to determine whether VPA use during radiotherapy for high-grade glioma is associated with decreased side effects of radiotherapy and an improvement in overall survival (OS) and progression-free survival (PFS). Medical records of 112 patients with high-grade glioma were retrospectively reviewed. We grouped patients by VPA use or non-use during radiotherapy, and evaluated hair loss, OS, and PFS. The radiation dose and fractionation at the onset of hair loss were 4 Gy and two fractions higher, respectively, in the VPA group compared with the VPA non-use group (P hair loss and improvement in survival. Hair loss prevention benefits patients suffering from the deleterious effects of radiation.

Local Control and Survival Following Concomitant Chemoradiotherapy in Inoperable Stage I Non-Small-Cell Lung Cancer

International Nuclear Information System (INIS)

Campeau, Marie-Pierre; Herschtal, Alan; Wheeler, Greg; Mac Manus, Michael; Wirth, Andrew; Michael, Michael; Hogg, Annette; Drummond, Elizabeth; Ball, David

2009-01-01

Purpose: Concomitant chemoradiotherapy (CRT) increases survival rates compared with radical radiotherapy alone (RT) in Stage III non-small-cell lung cancer (NSCLC), as a result of improved local control. The effect of CRT on local control in Stage I NSCLC is less well documented. We retrospectively reviewed local control and survival following CRT or RT for inoperable Stage I NSCLC patients. Methods and materials: Eligible patients had histologically/cytologically proved inoperable Stage I NSCLC and had undergone complete staging investigations including an F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) scan. Radiotherapy was planned as (1) 60 Gy in 30 fractions over 6 weeks with or without concomitant chemotherapy or (2) 50-55 Gy in 20 fractions without chemotherapy. Results: Between 2000 and 2005, 73 patients met the eligibility criteria and were treated as follows: CRT (60 Gy)-39; RT (60 Gy)-23; RT (50-55 Gy)-11. The median follow-up time for all patients was 18 months (range, 1-81 months). Survival analysis was based on intent to treat. Local progression-free survival (PFS) at 2 years was 66% with CRT and 55% with RT. The 2-year distant PFS was 60% following CRT and 63% after RT. The 2-year PFS rates were 57% and 50%, respectively. The 2-year survival rate for patients treated with CRT was 57% and 33% in patients receiving RT. Conclusions: Despite the use of CRT and routine staging with FDG-PET, both local and distant recurrences remain important causes of treatment failure in patients with inoperable stage I NSCLC.

Low-grade Glioma Surgery in Intraoperative Magnetic Resonance Imaging: Results of a Multicenter Retrospective Assessment of the German Study Group for Intraoperative Magnetic Resonance Imaging.

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Coburger, Jan; Merkel, Andreas; Scherer, Moritz; Schwartz, Felix; Gessler, Florian; Roder, Constantin; Pala, Andrej; König, Ralph; Bullinger, Lars; Nagel, Gabriele; Jungk, Christine; Bisdas, Sotirios; Nabavi, Arya; Ganslandt, Oliver; Seifert, Volker; Tatagiba, Marcos; Senft, Christian; Mehdorn, Maximilian; Unterberg, Andreas W; Rössler, Karl; Wirtz, Christian Rainer

2016-06-01

The ideal treatment strategy for low-grade gliomas (LGGs) is a controversial topic. Additionally, only smaller single-center series dealing with the concept of intraoperative magnetic resonance imaging (iMRI) have been published. To investigate determinants for patient outcome and progression-free-survival (PFS) after iMRI-guided surgery for LGGs in a multicenter retrospective study initiated by the German Study Group for Intraoperative Magnetic Resonance Imaging. A retrospective consecutive assessment of patients treated for LGGs (World Health Organization grade II) with iMRI-guided resection at 6 neurosurgical centers was performed. Eloquent location, extent of resection, first-line adjuvant treatment, neurophysiological monitoring, awake brain surgery, intraoperative ultrasound, and field-strength of iMRI were analyzed, as well as progression-free survival (PFS), new permanent neurological deficits, and complications. Multivariate binary logistic and Cox regression models were calculated to evaluate determinants of PFS, gross total resection (GTR), and adjuvant treatment. A total of 288 patients met the inclusion criteria. On multivariate analysis, GTR significantly increased PFS (hazard ratio, 0.44; P surgery. Patients with accidentally left tumor remnants showed a similar prognosis compared with patients harboring only partially resectable tumors. Use of high-field iMRI was significantly associated with GTR. However, the field strength of iMRI did not affect PFS. EoR, extent of resectionFLAIR, fluid-attenuated inversion recoveryGTR, gross total resectionIDH1, isocitrate dehydrogenase 1iMRI, intraoperative magnetic resonance imagingLGG, low-grade gliomaMGMT, methylguanine-deoxyribonucleic acid methyltransferasenPND, new permanent neurological deficitOS, overall survivalPFS, progression-free survivalSTR, subtotal resectionWHO, World Health Organization.

Efficacy of doxorubicin after progression on carboplatin and paclitaxel in advanced or recurrent endometrial cancer: a retrospective analysis of patients treated at the Brazilian National Cancer Institute (INCA).

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Moreira, Emeline; Paulino, Eduardo; Ingles Garces, Álvaro Henrique; Fontes Dias, Mariane S; Saramago, Marcos; de Moraes Lino da Silva, Flora; Thuler, Luiz Claudio Santos; de Melo, Andréia Cristina

2018-01-31

The treatment of endometrial cancer (EC) is challenging. There is no standard of care for patients who progressed after carboplatin and paclitaxel (CT) and all available drugs show a small response and poor long-term survival in this scenario. The objective of this study was to evaluate the efficacy and toxicity profile of palliative doxorubicin after progression to CT therapy in advanced or recurrent EC. A retrospective review of the Brazilian National Cancer Institute database between 2009 and 2013 was performed, and all patients with recurrent and advanced EC treated with palliative doxorubicin after progression on CT were included. Progression-free survival (PFS), overall survival (OS), objective response rates as well as toxicity were evaluated. A total of 33 patients were enrolled, with a median age of 65.7 years. Objective responses were documented in 12.1% (3.0% of complete responses and 9.1% of partial responses). The median PFS was 4.4 months, and the median OS was 8.1 months for patients exposed to doxorubicin. The most common adverse event was anemia observed in 60.6% of patients. This retrospective study suggests that doxorubicin has a modest activity in patients with advanced or recurrent EC after treatment with CT.

c-MET Overexpression in Colorectal Cancer: A Poor Prognostic Factor for Survival.

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Lee, Su Jin; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Kim, Seung Tae

2018-03-02

Increased mesenchymal-epithelial transition factor gene (c-MET) expression in several human malignancies is related to increased tumor progression and is a new potential drug target for several types of cancers. In the present study, we investigated the incidence of c-MET overexpression and its prognostic significance in patients with colorectal cancer (CRC). We retrospectively reviewed the data from 255 stage IV CRC patients who had results from a c-MET immunohistochemical test at Samsung Medical Center. We explored the relationships between c-MET overexpression and clinicopathological features and survival. Primary tumor sites were 67 right-sided colon, 98 left-sided colon, and 90 rectum. Forty-two patients (16.7%) had poorly differentiated or mucinous carcinoma. Among the 255 patients, 39 (15.3%) exhibited c-MET overexpression. There was no significant difference in the prevalence of c-MET overexpression according to primary site, histologic differentiation, molecular markers, or metastatic sites. In a comparison of the tumor response to first-line chemotherapy according to the level of c-MET expression, we found no significant difference in either partial response or disease control rate. In the survival analysis, patients with c-MET overexpression had significantly shorter overall survival (39 vs. 27 months; P = .018) and progression-free survival (PFS) during bevacizumab treatment (10 vs. 7 months; P = .024). c-MET overexpression, which was detected in 39 CRC patients (15.3%) irrespective of primary sites or molecular markers, indicated a poor survival prognosis and predicted shorter PFS during bevacizumab treatment in patients with CRC. Further studies are warranted to elucidate the value of c-MET-targeted therapy in CRC patients. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Economic evaluation of nivolumab for the treatment of second-line advanced squamous NSCLC in Canada: a comparison of modeling approaches to estimate and extrapolate survival outcomes.

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Goeree, Ron; Villeneuve, Julie; Goeree, Jeff; Penrod, John R; Orsini, Lucinda; Tahami Monfared, Amir Abbas

2016-06-01

Background Lung cancer is the most common type of cancer in the world and is associated with significant mortality. Nivolumab demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) for patients with advanced squamous non-small cell lung cancer (NSCLC) who were previously treated. The cost-effectiveness of nivolumab has not been assessed in Canada. A contentious component of projecting long-term cost and outcomes in cancer relates to the modeling approach adopted, with the two most common approaches being partitioned survival (PS) and Markov models. The objectives of this analysis were to estimate the cost-utility of nivolumab and to compare the results using these alternative modeling approaches. Methods Both PS and Markov models were developed using docetaxel and erlotinib as comparators. A three-health state model was used consisting of progression-free, progressed disease, and death. Disease progression and time to progression were estimated by identifying best-fitting survival curves from the clinical trial data for PFS and OS. Expected costs and health outcomes were calculated by combining health-state occupancy with medical resource use and quality-of-life assigned to each of the three health states. The health outcomes included in the model were survival and quality-adjusted-life-years (QALYs). Results Nivolumab was found to have the highest expected per-patient cost, but also improved per-patient life years (LYs) and QALYs. Nivolumab cost an additional $151,560 and $140,601 per QALY gained compared to docetaxel and erlotinib, respectively, using a PS model approach. The cost-utility estimates using a Markov model were very similar ($152,229 and $141,838, respectively, per QALY gained). Conclusions Nivolumab was found to involve a trade-off between improved patient survival and QALYs, and increased cost. It was found that the use of a PS or Markov model produced very similar estimates of expected cost

SU-E-J-254: Evaluating the Role of Mid-Treatment and Post-Treatment FDG-PET/CT in Predicting Progression-Free Survival and Distant Metastasis of Anal Cancer Patients Treated with Chemoradiotherapy

International Nuclear Information System (INIS)

Zhang, H; Wang, J; Chuong, M; D’Souza, W; Choi, W; Lu, W; Latifi, K; Hoffe, S; Moros, E; Saeed, Nadia; Tan, S; Shridhar, R

2015-01-01

Purpose: To evaluate the role of mid-treatment and post-treatment FDG-PET/CT in predicting progression-free survival (PFS) and distant metastasis (DM) of anal cancer patients treated with chemoradiotherapy (CRT). Methods: 17 anal cancer patients treated with CRT were retrospectively studied. The median prescription dose was 56 Gy (range, 50–62.5 Gy). All patients underwent FDG-PET/CT scans before and after CRT. 16 of the 17 patients had an additional FDG-PET/CT image at 3–5 weeks into the treatment (denoted as mid-treatment FDG-PET/CT). 750 features were extracted from these three sets of scans, which included both traditional PET/CT measures (SUVmax, SUVpeak, tumor diameters, etc.) and spatialtemporal PET/CT features (comprehensively quantify a tumor’s FDG uptake intensity and distribution, spatial variation (texture), geometric property and their temporal changes relative to baseline). 26 clinical parameters (age, gender, TNM stage, histology, GTV dose, etc.) were also analyzed. Advanced analytics including methods to select an optimal set of predictors and a model selection engine, which identifies the most accurate machine learning algorithm for predictive analysis was developed. Results: Comparing baseline + mid-treatment PET/CT set to baseline + posttreatment PET/CT set, 14 predictors were selected from each feature group. Same three clinical parameters (tumor size, T stage and whether 5-FU was held during any cycle of chemotherapy) and two traditional measures (pre- CRT SUVmin and SUVmedian) were selected by both predictor groups. Different mix of spatial-temporal PET/CT features was selected. Using the 14 predictors and Naive Bayes, mid-treatment PET/CT set achieved 87.5% accuracy (2 PFS patients misclassified, all local recurrence and DM patients correctly classified). Post-treatment PET/CT set achieved 94.0% accuracy (all PFS and DM patients correctly predicted, 1 local recurrence patient misclassified) with logistic regression, neural network or

SU-E-J-254: Evaluating the Role of Mid-Treatment and Post-Treatment FDG-PET/CT in Predicting Progression-Free Survival and Distant Metastasis of Anal Cancer Patients Treated with Chemoradiotherapy

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Zhang, H; Wang, J; Chuong, M; D’Souza, W; Choi, W; Lu, W [University of Maryland School of Medicine, Baltimore, MD (United States); Latifi, K; Hoffe, S; Moros, E [Moffitt Cancer Center, Tampa, FL (United States); Saeed, Nadia [Brwon University, Providence, RI (United States); Tan, S [Huazhong University of Science & Technology, Wuhan (China); Shridhar, R [Florida Hospital, Orlando, FL (United States)

2015-06-15

Purpose: To evaluate the role of mid-treatment and post-treatment FDG-PET/CT in predicting progression-free survival (PFS) and distant metastasis (DM) of anal cancer patients treated with chemoradiotherapy (CRT). Methods: 17 anal cancer patients treated with CRT were retrospectively studied. The median prescription dose was 56 Gy (range, 50–62.5 Gy). All patients underwent FDG-PET/CT scans before and after CRT. 16 of the 17 patients had an additional FDG-PET/CT image at 3–5 weeks into the treatment (denoted as mid-treatment FDG-PET/CT). 750 features were extracted from these three sets of scans, which included both traditional PET/CT measures (SUVmax, SUVpeak, tumor diameters, etc.) and spatialtemporal PET/CT features (comprehensively quantify a tumor’s FDG uptake intensity and distribution, spatial variation (texture), geometric property and their temporal changes relative to baseline). 26 clinical parameters (age, gender, TNM stage, histology, GTV dose, etc.) were also analyzed. Advanced analytics including methods to select an optimal set of predictors and a model selection engine, which identifies the most accurate machine learning algorithm for predictive analysis was developed. Results: Comparing baseline + mid-treatment PET/CT set to baseline + posttreatment PET/CT set, 14 predictors were selected from each feature group. Same three clinical parameters (tumor size, T stage and whether 5-FU was held during any cycle of chemotherapy) and two traditional measures (pre- CRT SUVmin and SUVmedian) were selected by both predictor groups. Different mix of spatial-temporal PET/CT features was selected. Using the 14 predictors and Naive Bayes, mid-treatment PET/CT set achieved 87.5% accuracy (2 PFS patients misclassified, all local recurrence and DM patients correctly classified). Post-treatment PET/CT set achieved 94.0% accuracy (all PFS and DM patients correctly predicted, 1 local recurrence patient misclassified) with logistic regression, neural network or

Diffuse intrinsic pontine glioma in children and adolescents: a single-center experience.

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Vallero, Stefano Gabriele; Bertin, Daniele; Basso, Maria Eleonora; Pittana, Laura Stefania; Mussano, Anna; Fagioli, Franca

2014-06-01

Patients with diffuse intrinsic pontine glioma (DIPG) have a very poor prognosis. Only radiotherapy (XRT) has proven to be effective in delaying the disease progression. Several chemotherapy schedules have been applied so far, but none demonstrated significant improvements in progression and survival. We retrospectively analyzed the clinical data of children diagnosed with DIPG at our center (Pediatric Hospital "Regina Margherita," Turin, Italy) between 1999 and 2013. Progression-free survival (PFS) and overall survival (OS) were used to describe the outcomes. Twenty-four children were included in our report. Patients diagnosed before March 2003 (n = 12) were treated with XRT and vincristine (VCR); the remaining 12 patients received XRT and temozolomide (TMZ). Progression-free survival was 18.8 % at 1 year (SE = 7.6 %), while overall survival was 44.1 % at 1 year (SE = 9.9 %). Median PFS was 8.1 months, whereas median OS was 11.2 months. No statistically significant difference in PFS or OS was evidenced between the two treatment groups. Radiotherapy followed by VCR or TMZ allows obtaining results that are in line with previous reports, with no advantages over other similar treatment schedules. DIPGs are challenging tumors with a dismal outcome. Further research and newer therapies are urgently needed in order to achieve improvements in survival.

TP53 hotspot mutations are predictive of survival in primary central nervous system lymphoma patients treated with combination chemotherapy

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Munch-Petersen, Helga D; Asmar, Fazila; Dimopoulos, Konstantinos

2016-01-01

regimens (high-dose methotrexate/whole brain radiation therapy, 6.0 months, or no therapy, 0.83 months), P hotspot/direct DNA contact mutations. CCT-treated patients with PCNSL harboring a hotspot/direct DNA contact MUT......-TP53 (n = 9) had a significantly worse OS and progression free survival (PFS) compared to patients with non-hotspot/non-direct DNA contact MUT-TP53 or wild-type TP53 (median PFS 4.6 versus 18.2 or 45.7 months), P = 0.041 and P = 0.00076, respectively. Multivariate Cox regression analysis confirmed...... that hotspot/direct DNA contact MUT-TP53 was predictive of poor outcome in CCT-treated PCNSL patients, P = 0.012 and P = 0.008; HR: 1.86 and 1.95, for OS and PFS, respectively. MIR34A, MIR34B/C, and DAPK promoter methylation were detected in 53/93 (57.0 %), 80/84 (95.2 %), and 70/75 (93.3 %) of the PCNSL...

A retrospective review of outcome and survival following surgery and adjuvant xenogeneic DNA vaccination in 32 dogs with oral malignant melanoma.

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Treggiari, Elisabetta; Grant, Jessica Pauline; North, Susan Margaret

2016-06-01

A xenogeneic DNA vaccination has been licensed for use in dogs with locally controlled stage II and III oral malignant melanoma (OMM). At present, there are limited outcome data for dogs with OMM treated with surgery and immunotherapy. The aim of this study is to retrospectively review the outcome and survival of 32 dogs affected by OMM that were treated with a combination of surgery and the xenogeneic DNA vaccination (with the addition of radiotherapy in some cases) and to determine the influence of surgical margins and delay in receiving vaccination. The overall median survival time (MST) was 335 days (95% CI: 301-540 days), and the overall median progression-free survival (PFS) was 160 days (mean 182 days, 95% CI: 132-232 days). Stage, completeness of surgical margins and delay in administration of the vaccine did not appear to statistically influence survival or PFS, although these results may reflect the low statistical power of the study due to small numbers. Further studies are required to assess whether the addition of any adjuvant treatment to surgery, including immunotherapy, is able to significantly prolong survival in cases of canine oral melanoma.

Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates.

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Jones, Sophie; Grignard, Lynn; Nebie, Issa; Chilongola, Jaffu; Dodoo, Daniel; Sauerwein, Robert; Theisen, Michael; Roeffen, Will; Singh, Shrawan Kumar; Singh, Rajesh Kumar; Singh, Sanjay; Kyei-Baafour, Eric; Tetteh, Kevin; Drakeley, Chris; Bousema, Teun

2015-07-01

Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences for the future evaluation of vaccine immunogenicity and efficacy in populations naturally exposed to malaria. We determined naturally acquired antibody responses to the recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three malaria endemic settings in Ghana, Tanzania and Burkina Faso. We also examined genetic polymorphisms in the P. falciparum gene pfs48/45. Antibody prevalence was 1.1-18.2% for 10C and 6.7-18.9% for 230CMB. In Burkina Faso we observed evidence of an age-dependent acquisition pattern for both 10C (p < 0.001) and 230CMB (p = 0.031). Membrane feeding assays on a separate dataset demonstrated an association between functional transmission reducing activity and antibody prevalence for both 10C (p = 0.017) and 230CMB (p = 0.049). 17 single nucleotide polymorphisms were found in pfs48/45 (from 126 samples), with 5 non-synonymous SNPs in the Pfs48/45 10C region. We conclude there are naturally acquired antibody responses to both vaccine candidates which have functional relevance by reducing the transmissibility of infected individuals. We identified genetic polymorphisms, in pfs48/45 which exhibited geographical specificity. Copyright © 2015 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates

DEFF Research Database (Denmark)

Jones, Sophie; Grignard, Lynn; Nebie, Issa

2015-01-01

for the future evaluation of vaccine immunogenicity and efficacy in populations naturally exposed to malaria. METHODS: We determined naturally acquired antibody responses to the recombinant proteins Pfs48/45-10C and Pfs230-230CMB in children from three malaria endemic settings in Ghana, Tanzania and Burkina Faso......OBJECTIVES: Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences....... We also examined genetic polymorphisms in the P. falciparum gene pfs48/45. RESULTS: Antibody prevalence was 1.1-18.2% for 10C and 6.7-18.9% for 230CMB. In Burkina Faso we observed evidence of an age-dependent acquisition pattern for both 10C (p assays...

Single agent vinorelbine in pediatric patients with progressive optic pathway glioma.

Science.gov (United States)

Cappellano, Andrea Maria; Petrilli, Antonio Sergio; da Silva, Nasjla Saba; Silva, Frederico Adolfo; Paiva, Priscila Mendes; Cavalheiro, Sergio; Bouffet, Eric

2015-01-01

The management of progressive unresectable low-grade glioma remains controversial. Treatment options have included radiotherapy, and more recently chemotherapy, usually following an initial period of observation. Within this context, we evaluated vinorelbine, a semi-synthetic vinca alkaloid that has shown evidence of activity against glioma. From July 2007 an institutional protocol with vinorelbine (30 mg/m(2) days 0, 8, 22) for a total of 18 cycles, has been conducted at IOP/GRAACC/UNIFESP for children with optic pathway glioma (OPG). The main objectives were clinical and radiological response, as well as toxicity profile. Twenty-three patients with progressive OPG with a mean age of 69 months (4-179) were enrolled. Three patients had a diagnosis of neurofibromatosis type 1. Twenty-two patients were assessable for response with an overall objective response rate of 63 %, with eight patients showing stable disease. The most important toxicity was hematologic (grade III/IV neutropenia) observed in four patients. Gastrointestinal toxicity (grade I/II vomiting) was observed in seven patients and only 1 patient showed grade I peripheral neuropathy. The median progression-free survival (PFS) was 33 months (6.9-69) with a 3 and 5 year PFS of 64 ± 19 and 37 ± 20 %, respectively, for an overall 3 and 5 year-survival of 95 ± 10 %. This study suggests that vinorelbine may be an interesting option for pediatric low-grade gliomas, showing low toxicity profile and providing a good quality of life for patients with such chronic disease.

The effect of adjuvant radiation on survival in early stage clear cell ovarian carcinoma.

Science.gov (United States)

Hogen, Liat; Thomas, Gillian; Bernardini, Marcus; Bassiouny, Dina; Brar, Harinder; Gien, Lilian T; Rosen, Barry; Le, Lisa; Vicus, Danielle

2016-11-01

To assess the impact of adjuvant radiotherapy (RT) on survival in patients with stage I and II ovarian clear cell carcinoma (OCCC). Data collection and analysis of stage I and II OCCC patients treated at two tertiary centers in Toronto, between 1995 and 2014, was performed. Descriptive statistics and Kaplan-Meier survival probability estimates were completed. The log-rank test was used to compare survival curves. 163 patients were eligible. 44 (27%) patients were treated with adjuvant RT: 37 of them received adjuvant chemotherapy (CT), and 7 had RT only. In the no-RT group, there were 119 patients: 83 patients received adjuvant CT and 36 had no adjuvant treatment. The 10year progression free survival (PFS) was 65% for patients treated with RT, and 59% no-RT patients. There were a total of 41 (25%) recurrences in the cohort: 12 (27.2%) patients in RT group and 29 (24.3%) in the no-RT group. On multivariable analysis, adjuvant RT was not significantly associated with an increased PFS (0.85 (0.44-1.63) p=0.63) or overall survival (OS) (0.84 (0.39-1.82) p=0.66). In the subset of 59 patients defined as high-risk: stage IC with positive cytology and/or surface involvement and stage II: RT was not found to be associated with a better PFS (HR 1.18 (95% CI: 0.55-2.54) or O S(HR 1.04 (95% CI: 0.40-2.69)). Adjuvant RT was not found to be associated with a survival benefit in patients with stage I and II ovarian clear cell carcinoma or in a high risk subset of patients including stage IC cytology positive/surface involvement and stage II patients. Copyright © 2016 Elsevier Inc. All rights reserved.

Survival effect of first- and second-line treatments for patients with primary glioblastoma: a cohort study from a prospective registry, 1997-2010.

Science.gov (United States)

Nava, Francesca; Tramacere, Irene; Fittipaldo, Andrea; Bruzzone, Maria Grazia; Dimeco, Francesco; Fariselli, Laura; Finocchiaro, Gaetano; Pollo, Bianca; Salmaggi, Andrea; Silvani, Antonio; Farinotti, Mariangela; Filippini, Graziella

2014-05-01

Prospective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010. Survival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004-2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997-2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively. Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II). We found a significant increase in overall survival, PFS, and survival after recurrence after 2004, likely due to

Survival and human papillomavirus in oropharynx cancer in TAX 324: a subset analysis from an international phase III trial.

Science.gov (United States)

Posner, M R; Lorch, J H; Goloubeva, O; Tan, M; Schumaker, L M; Sarlis, N J; Haddad, R I; Cullen, K J

2011-05-01

The association between human papillomavirus (HPV) and overall survival (OS) in oropharynx cancer (OPC) was retrospectively examined in TAX 324, a phase III trial of sequential therapy for locally advanced head and neck cancer. Accrual for TAX 324 was completed in 2003 and data updated through 2008. Pretherapy tumor biopsies were studied by PCR for human papillomavirus type 16 and linked to OS, progression-free survival (PFS) and demographics. Of 264 patients with OPC, 111 (42%) had evaluable biopsies; 56 (50%) were HPV+ and 55 (50%) were HPV-. HPV+ patients were significantly younger (54 versus 58 years, P = 0.02), had T1/T2 primary cancers (49% versus 20%, P = 0.001), and had a performance status of zero (77% versus 49%, P = 0.003). OS and PFS were better for HPV+ patients (OS, hazard ratio = 0.20, P < 0.0001). Local-regional failure was less in HPV+ patients (13% versus 42%, P = 0.0006); at 5 years, 82% of HPV+ patients were alive compared with 35% of HPV- patients (P < 0.0001). HPV+ OPC has a different biology compared with HPV- OPC; 5-year OS, PFS, and local-regional control are unprecedented. These results support the possibility of selectively reducing therapy and long-term morbidity in HPV+ OPC while preserving survival and approaching HPV- disease with more aggressive treatment.

Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials)

NARCIS (Netherlands)

Bonnetain, Franck; Bonsing, Bert; Conroy, Thierry; Dousseau, Adelaide; Glimelius, Bengt; Haustermans, Karin; Lacaine, François; van Laethem, Jean Luc; Aparicio, Thomas; Aust, Daniela; Bassi, Claudio; Berger, Virginie; Chamorey, Emmanuel; Chibaudel, Benoist; Dahan, Laeticia; de Gramont, Aimery; Delpero, Jean Robert; Dervenis, Christos; Ducreux, Michel; Gal, Jocelyn; Gerber, Erich; Ghaneh, Paula; Hammel, Pascal; Hendlisz, Alain; Jooste, Valérie; Labianca, Roberto; Latouche, Aurelien; Lutz, Manfred; Macarulla, Teresa; Malka, David; Mauer, Muriel; Mitry, Emmanuel; Neoptolemos, John; Pessaux, Patrick; Sauvanet, Alain; Tabernero, Josep; Taieb, Julien; van Tienhoven, Geertjan; Gourgou-Bourgade, Sophie; Bellera, Carine; Mathoulin-Pélissier, Simone; Collette, Laurence

2014-01-01

Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across

Being treated in higher volume hospitals leads to longer progression-free survival for epithelial ovarian carcinoma patients in the Rhone-Alpes region of France

OpenAIRE

Huguet, Marius; Perrier, Lionel; Bally, Olivia; Benayoun, David; De Saint Hilaire, Pierre; Beal Ardisson, Dominique; Morelle, Magali; Havet, Nathalie; Joutard, Xavier; Meeus, Pierre; Gabelle, Philippe; Provençal, Jocelyne; Chauleur, Céline; Glehen, Olivier; Charreton, Amandine

2018-01-01

Background To investigate the relationship between hospital volume activities and the survival for Epithelial Ovarian Carcinoma (EOC) patients in France. Methods This retrospective study using prospectively implemented databases was conducted on an exhaustive cohort of 267 patients undergoing first-line therapy during 2012 in the Rhone-Alpes Region of France. We compared Progression-Free Survival for Epithelial Ovarian Carcinoma patients receiving first-line therapy in high- (i.e. ≥ 12 cases/...

Cost-Effectiveness of Everolimus for Second-Line Treatment of Metastatic Renal Cell Carcinoma in Serbia

NARCIS (Netherlands)

Mihajlovic, Jovan; Pechlivanoglou, Petros; Sabo, Ana; Tomic, Zdenko; Postma, Maarten J.

2013-01-01

Background: New targeted therapeutics for metastatic renal cell carcinoma (mRCC) enable an increment in progression-free survival (PFS) ranging from 2 to 6 months. Compared with best supportive care, everolimus demonstrated an additional PFS of 3 months in patients with mRCC whose disease had

Additional Survival Benefit of Involved-Lesion Radiation Therapy After R-CHOP Chemotherapy in Limited Stage Diffuse Large B-Cell Lymphoma

Energy Technology Data Exchange (ETDEWEB)

Kwon, Jeanny [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Il Han, E-mail: ihkim@snu.ac.kr [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Cancer Research Institute, Seoul National University College of Medicine, Seoul (Korea, Republic of); Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul (Korea, Republic of); Kim, Byoung Hyuck [Department of Radiation Oncology, Seoul National University College of Medicine, Seoul (Korea, Republic of); Kim, Tae Min; Heo, Dae Seog [Department of Internal Medicine, Seoul National University Hospital, Seoul (Korea, Republic of)

2015-05-01

Purpose: The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. Methods and Materials: We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥7 cm); and 75.3% underwent ≥6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). Results: After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Conclusions: Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level.

Additional survival benefit of involved-lesion radiation therapy after R-CHOP chemotherapy in limited stage diffuse large B-cell lymphoma.

Science.gov (United States)

Kwon, Jeanny; Kim, Il Han; Kim, Byoung Hyuck; Kim, Tae Min; Heo, Dae Seog

2015-05-01

The purpose of this study was to evaluate the role of involved-lesion radiation therapy (ILRT) after rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy in limited stage diffuse large B-cell lymphoma (DLBCL) by comparing outcomes of R-CHOP therapy alone with R-CHOP followed by ILRT. We identified 198 patients treated with R-CHOP (median, 6 cycles) for pathologically confirmed DLBCL of limited stage from July 2004 to December 2012. Clinical characteristics of these patients were 33% with stage I and 66.7% with stage II; 79.8% were in the low or low-intermediate risk group; 13.6% had B symptoms; 29.8% had bulky tumors (≥ 7 cm); and 75.3% underwent ≥ 6 cycles of R-CHOP therapy. RT was given to 43 patients (21.7%) using ILRT technique, which included the prechemotherapy tumor volume with a median margin of 2 cm (median RT dose: 36 Gy). After a median follow-up of 40 months, 3-year progression-free survival (PFS) and overall survival (OS) were 85.8% and 88.9%, respectively. Multivariate analysis showed ≥ 6 cycles of R-CHOP (PFS, P=.004; OS, P=.004) and ILRT (PFS, P=.021; OS, P=.014) were favorable prognosticators of PFS and OS. A bulky tumor (P=.027) and response to R-CHOP (P=.012) were also found to be independent factors of OS. In subgroup analysis, the effect of ILRT was prominent in patients with a bulky tumor (PFS, P=.014; OS, P=.030) or an elevated level of serum lactate dehydrogenase (LDH; PFS, P=.004; OS, P=.012). Our results suggest that ILRT after R-CHOP therapy improves PFS and OS in patients with limited stage DLBCL, especially in those with bulky disease or an elevated serum LDH level. Copyright © 2015. Published by Elsevier Inc.

Survival Advantage With the Addition of Radiation Therapy to Chemotherapy in Early Stage Peripheral T-Cell Lymphoma, Not Otherwise Specified

International Nuclear Information System (INIS)

Zhang, Xi-Mei; Li, Ye-Xiong; Wang, Wei-Hu; Jin, Jing; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Fang, Hui; Ren, Hua; Zhou, Li-Qiang; Liu, Xin-Fan; Yu, Zi-Hao

2013-01-01

Purpose: Early stage peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is rare. The purpose of this study was to evaluate the outcome of treatment as well as the potential role of radiation therapy in PTCL-NOS. Methods and Materials: Thirty-five patients with early stage PTCL-NOS were included. There were 13 patients with stage I disease and 22 with stage II. All patients except 1 received doxorubicin-based chemotherapy alone (n=13) or a combination of chemotherapy and radiation therapy (CMT) (n=21). Results: The 3-year overall survival (OS) and progression-free survival (PFS) rates for the entire group were 41.3% and 25.7%, respectively. The addition of radiation therapy to chemotherapy significantly improved OS and PFS in early stage PTCL-NOS. The 3-year OS and PFS rates were 49.7% and 33.3% for CMT, compared with 23.1% (P=.042) and 15.4% (P=.035) for chemotherapy alone, respectively. The prognosis for patients who achieved a complete response (CR) was significantly better than that observed in those who did not achieve a CR. Conclusions: Despite the aggressive clinical course of early stage PTCL-NOS, additional radiation therapy has a significant impact on outcome. The integration of local radiation therapy into more effective systemic therapies may further improve survival

Survival Advantage With the Addition of Radiation Therapy to Chemotherapy in Early Stage Peripheral T-Cell Lymphoma, Not Otherwise Specified

Energy Technology Data Exchange (ETDEWEB)

Zhang, Xi-Mei [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Li, Ye-Xiong, E-mail: yexiong@yahoo.com [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Wang, Wei-Hu; Jin, Jing; Wang, Shu-Lian; Liu, Yue-Ping; Song, Yong-Wen; Fang, Hui; Ren, Hua [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Zhou, Li-Qiang [Department of Medical Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China); Liu, Xin-Fan; Yu, Zi-Hao [Department of Radiation Oncology, Cancer Hospital and Institution, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing (China)

2013-03-15

Purpose: Early stage peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) is rare. The purpose of this study was to evaluate the outcome of treatment as well as the potential role of radiation therapy in PTCL-NOS. Methods and Materials: Thirty-five patients with early stage PTCL-NOS were included. There were 13 patients with stage I disease and 22 with stage II. All patients except 1 received doxorubicin-based chemotherapy alone (n=13) or a combination of chemotherapy and radiation therapy (CMT) (n=21). Results: The 3-year overall survival (OS) and progression-free survival (PFS) rates for the entire group were 41.3% and 25.7%, respectively. The addition of radiation therapy to chemotherapy significantly improved OS and PFS in early stage PTCL-NOS. The 3-year OS and PFS rates were 49.7% and 33.3% for CMT, compared with 23.1% (P=.042) and 15.4% (P=.035) for chemotherapy alone, respectively. The prognosis for patients who achieved a complete response (CR) was significantly better than that observed in those who did not achieve a CR. Conclusions: Despite the aggressive clinical course of early stage PTCL-NOS, additional radiation therapy has a significant impact on outcome. The integration of local radiation therapy into more effective systemic therapies may further improve survival.

Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

International Nuclear Information System (INIS)

Chen, James X.; Rose, Steven; White, Sarah B.; El-Haddad, Ghassan; Fidelman, Nicholas; Yarmohammadi, Hooman; Hwang, Winifred; Sze, Daniel Y.; Kothary, Nishita; Stashek, Kristen; Wileyto, E. Paul; Salem, Riad; Metz, David C.; Soulen, Michael C.

2017-01-01

PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Cox proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p  50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.

Embolotherapy for Neuroendocrine Tumor Liver Metastases: Prognostic Factors for Hepatic Progression-Free Survival and Overall Survival

Energy Technology Data Exchange (ETDEWEB)

Chen, James X. [Hospital of the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States); Rose, Steven [University of San Diego Medical Center, Division of Interventional Radiology, Department of Radiology (United States); White, Sarah B. [Medical College of Wisconsin, Division of Interventional Radiology, Department of Radiology (United States); El-Haddad, Ghassan [Moffitt Cancer Center, Division of Interventional Radiology, Department of Radiology (United States); Fidelman, Nicholas [University of San Francisco Medical Center, Division of Interventional Radiology, Department of Radiology (United States); Yarmohammadi, Hooman [Memorial Sloan Kettering Cancer Center, Division of Interventional Radiology, Department of Radiology (United States); Hwang, Winifred; Sze, Daniel Y.; Kothary, Nishita [Stanford University Medical Center, Division of Interventional Radiology, Department of Radiology (United States); Stashek, Kristen [Hospital of the University of Pennsylvania, Department of Pathology (United States); Wileyto, E. Paul [University of Pennsylvania, Department of Biostatistics and Epidemiology (United States); Salem, Riad [Northwestern Memorial Hospital, Division of Interventional Radiology, Department of Radiology (United States); Metz, David C. [Hospital of the University of Pennsylvania, Division of Gastroenterology, Department of Medicine (United States); Soulen, Michael C., E-mail: michael.soulen@uphs.upenn.edu [Hospital of the University of Pennsylvania, Division of Interventional Radiology, Department of Radiology (United States)

2017-01-15

PurposeThe purpose of the study was to evaluate prognostic factors for survival outcomes following embolotherapy for neuroendocrine tumor (NET) liver metastases.Materials and MethodsThis was a multicenter retrospective study of 155 patients (60 years mean age, 57 % male) with NET liver metastases from pancreas (n = 71), gut (n = 68), lung (n = 8), or other/unknown (n = 8) primary sites treated with conventional transarterial chemoembolization (TACE, n = 50), transarterial radioembolization (TARE, n = 64), or transarterial embolization (TAE, n = 41) between 2004 and 2015. Patient-, tumor-, and treatment-related factors were evaluated for prognostic effect on hepatic progression-free survival (HPFS) and overall survival (OS) using unadjusted and propensity score-weighted univariate and multivariate Cox proportional hazards models.ResultsMedian HPFS and OS were 18.5 and 125.1 months for G1 (n = 75), 12.2 and 33.9 months for G2 (n = 60), and 4.9 and 9.3 months for G3 tumors (n = 20), respectively (p < 0.05). Tumor burden >50 % hepatic volume demonstrated 5.5- and 26.8-month shorter median HPFS and OS, respectively, versus burden ≤50 % (p < 0.05). There were no significant differences in HPFS or OS between gut or pancreas primaries. In multivariate HPFS analysis, there were no significant differences among embolotherapy modalities. In multivariate OS analysis, TARE had a higher hazard ratio than TACE (unadjusted Cox model: HR 2.1, p = 0.02; propensity score adjusted model: HR 1.8, p = 0.11), while TAE did not differ significantly from TACE.ConclusionHigher tumor grade and tumor burden prognosticated shorter HPFS and OS. TARE had a higher hazard ratio for OS than TACE. There were no significant differences in HPFS among embolotherapy modalities.

Very Early PSA Response to Abiraterone in mCRPC Patients: A Novel Prognostic Factor Predicting Overall Survival.

Science.gov (United States)

Facchini, Gaetano; Caffo, Orazio; Ortega, Cinzia; D'Aniello, Carmine; Di Napoli, Marilena; Cecere, Sabrina C; Della Pepa, Chiara; Crispo, Anna; Maines, Francesca; Ruatta, Fiorella; Iovane, Gelsomina; Pisconti, Salvatore; Montella, Maurizio; Berretta, Massimiliano; Pignata, Sandro; Cavaliere, Carla

2016-01-01

Abiraterone Acetate (AA) is approved for the treatment of mCRPC after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated and for treatment of mCRPC progressed during or after docetaxel-based chemotherapy regimen. The aim of this study is to evaluate the role of early PSA decline for detection of therapy success or failure in mCRPC patients treated with AA in post chemotherapy setting. We retrospectively evaluated 87 patients with mCRPC treated with AA. Serum PSA levels were evaluated after 15, 90 days and then monthly. The PSA flare phenomenon was evaluated, according to a confirmation value at least 1 week apart. The primary endpoint was to demonstrate that an early PSA decline correlates with a longer progression free survival (PFS) and overall survival (OS). The secondary endpoind was to demonstrate a correlation between better outcome and demographic and clinical patient characteristics. We have collected data of 87 patients between Sep 2011 and Sep 2014. Early PSA response (≥50% from baseline at 15 days) was found in 56% evaluated patients and confirmed in 29 patients after 90 days. The median PFS was 5.5 months (4.6-6.5) and the median OS was 17.1 months (8.8-25.2). In early responders patients (PSA RR ≥ 50% at 15 days), we found a significant statistical advantage in terms of PFS at 1 year, HR 0.28, 95%CI 0.12-0.65, p = 0.003, and OS, HR 0.21 95% CI 0.06-0.72, p = 0.01. The results in PFS at 1 years and OS reached statistical significance also in the evaluation at 90 days. A significant proportion (78.6%) of patients achieved a rapid response in terms of PSA decline. Early PSA RR (≥50% at 15 days after start of AA) can provide clinically meaningful information and can be considered a surrogate of longer PFS and OS.

The impact of time between staging PET/CT and definitive chemo-radiation on target volumes and survival in patients with non-small cell lung cancer

International Nuclear Information System (INIS)

Everitt, Sarah; Plumridge, Nikki; Herschtal, Alan; Bressel, Mathias; Ball, David; Callahan, Jason; Kron, Tomas; Schneider-Kolsky, Michal; Binns, David; Hicks, Rodney J.

2013-01-01

Background and purpose: To investigate the impact of treatment delays on radiation therapy (RT) target volumes and overall survival (OS) in patients with non-small cell lung cancer (NSCLC) who underwent two baseline FDG PET/CT scans. Material and methods: Patients underwent a staging (PET1) and RT planning (PET2) FDG PET/CT scan. At PET1 all patients were eligible for radical chemo-RT. OS and progression-free survival (PFS) were compared for patients remaining eligible for radical RT and those treated palliatively because PET2 showed progression. RT target volumes were contoured using PET1 and PET2. Normal tissue doses were compared for patients remaining eligible for radical RT. Results: Eighty-two patients underwent PET2 scans between October 2004 and February 2007. Of these, 21 had a prior PET1 scan, median 23 days apart (range 8–176 days). Six patients (29%) were unsuitable for radical RT after PET2; five received palliative treatment and one received no treatment. Patients treated palliatively had significantly worse OS and PFS than patients treated radically p < 0.001. Mean RT tumour volume increased from 105cc to 198cc (p < 0.005) between scans. Conclusions: Disease progression while awaiting initiation of curative RT in NSCLC is associated with larger treatment volumes and worse survival

PET/CT Improves the Definition of Complete Response and Allows to Detect Otherwise Unidentifiable Skeletal Progression in Multiple Myeloma.

Science.gov (United States)

Zamagni, Elena; Nanni, Cristina; Mancuso, Katia; Tacchetti, Paola; Pezzi, Annalisa; Pantani, Lucia; Zannetti, Beatrice; Rambaldi, Ilaria; Brioli, Annamaria; Rocchi, Serena; Terragna, Carolina; Martello, Marina; Marzocchi, Giulia; Borsi, Enrica; Rizzello, Ilaria; Fanti, Stefano; Cavo, Michele

2015-10-01

To evaluate the role of 18F-FDG PET/CT in 282 symptomatic multiple myeloma patients treated up-front between 2002 and 2012. All patients were studied by PET/CT at baseline, during posttreatment follow-up, and at the time of relapse. Their median duration of follow-up was 67 months. Forty-two percent of the patients at diagnosis had >3 focal lesions, and in 50% SUVmax was >4.2; extramedullary disease was present in 5%. On multivariate analysis, ISS stage 3, SUVmax >4.2, and failure to achieve best complete response (CR) were the leading factors independently associated with shorter progression-free survival (PFS) and overall survival (OS). These 3 variables were used to construct a prognostic scoring system based on the number of risk factors. After treatment, PET/CT negativity (PET-neg) was observed in 70% of patients, whereas conventionally defined CR was achieved in 53%. Attainment of PET-neg favorably influenced PFS and OS. PET-neg was an independent predictor of prolonged PFS and OS for patients with conventionally defined CR. Sixty-three percent of patients experienced relapse or progression; in 12%, skeletal progression was exclusively detected by systematic PET/CT performed during follow-up. A multivariate analysis revealed that persistence of SUVmax >4.2 following first-line treatment was independently associated with exclusive PET/CT progression. PET/CT combined with ISS stage and achievement or not of CR on first-line therapy sorted patients into different prognostic groups. PET/CT led to a more careful evaluation of CR. Finally, in patients with persistent high glucose metabolism after first-line treatment, PET/CT can be recommended during follow-up, to screen for otherwise unidentifiable progression. ©2015 American Association for Cancer Research.

How to Deal with Interval-Censored Data Practically while Assessing the Progression-Free Survival: A Step-by-Step Guide Using SAS and R Software.

Science.gov (United States)

Dugué, Audrey Emmanuelle; Pulido, Marina; Chabaud, Sylvie; Belin, Lisa; Gal, Jocelyn

2016-12-01

We describe how to estimate progression-free survival while dealing with interval-censored data in the setting of clinical trials in oncology. Three procedures with SAS and R statistical software are described: one allowing for a nonparametric maximum likelihood estimation of the survival curve using the EM-ICM (Expectation and Maximization-Iterative Convex Minorant) algorithm as described by Wellner and Zhan in 1997; a sensitivity analysis procedure in which the progression time is assigned (i) at the midpoint, (ii) at the upper limit (reflecting the standard analysis when the progression time is assigned at the first radiologic exam showing progressive disease), or (iii) at the lower limit of the censoring interval; and finally, two multiple imputations are described considering a uniform or the nonparametric maximum likelihood estimation (NPMLE) distribution. Clin Cancer Res; 22(23); 5629-35. ©2016 AACR. ©2016 American Association for Cancer Research.

Safety assessment of plant food supplements (PFS)

NARCIS (Netherlands)

Berg, van den S.J.P.L.; Serra-Majem, L.; Coppens, P.; Rietjens, I.

2011-01-01

Botanicals and botanical preparations, including plant food supplements (PFS), are widely used in Western diets. The growing use of PFS is accompanied by an increasing concern because the safety of these PFS is not generally assessed before they enter the market. Regulatory bodies have become more

Survival benefit of levetiracetam in patients treated with concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide for glioblastoma multiforme.

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Kim, Young-Hoon; Kim, Tackeun; Joo, Jin-Deok; Han, Jung Ho; Kim, Yu Jung; Kim, In Ah; Yun, Chang-Ho; Kim, Chae-Yong

2015-09-01

A chemosensitizing effect of levetiracetam (LEV) has been suggested because LEV inhibits O-6 methylguanine-DNA methyltransferase (MGMT). However, the survival benefit of LEV has not been clinically documented. The objective of this study was to assess the survival benefit of LEV compared with other antiepileptic drugs as a chemosensitizer to temozolomide for patients with glioblastoma. In total, 103 consecutive patients with primary glioblastoma who received concomitant chemoradiotherapy and adjuvant chemotherapy with temozolomide were retrospectively reviewed, and 58 patients (56%) received LEV during temozolomide chemotherapy for at least 3 months. A Cox regression survival analysis was performed to adjust for confounding factors, including age, extent of lesion, Karnofsky performance scale score, extent of removal, and MGMT promoter methylation status. The median progression-free survival (PFS) and overall survival (OS) for patients who received LEV in combination with temozolomide (PFS: median, 9.4 months; 95% confidence interval [CI], 7.5-11.3 months; OS: median, 25.7 months; 95% CI, 21.7-29.7 months) were significantly longer than those for patients who did not receive LEV (PFS: median, 6.7 months; 95% CI, 5.8-7.6 months; OS: median, 16.7 months; 95% CI, 12.1-21.3 months; P = .010 and P = .027, respectively). In multivariate analysis, the variables that were identified as significant prognostic factors for OS were preoperative Karnofsky performance scale score (hazard ratio [HR], 0.37; P = .016), MGMT promoter methylation (HR, 0.30; P = .002), and receipt of LEV (HR, 0.31; P benefit in patients with glioblastoma who receive temozolomide-based chemotherapy. A prospective randomized study may be indicated. © 2015 American Cancer Society.

Low MAD2 expression levels associate with reduced progression-free survival in patients with high-grade serous epithelial ovarian cancer.

LENUS (Irish Health Repository)

Furlong, Fiona

2012-04-01

Epithelial ovarian cancer (EOC) has an innate susceptibility to become chemoresistant. Up to 30% of patients do not respond to conventional chemotherapy [paclitaxel (Taxol®) in combination with carboplatin] and, of those who have an initial response, many patients relapse. Therefore, an understanding of the molecular mechanisms that regulate cellular chemotherapeutic responses in EOC cells has the potential to impact significantly on patient outcome. The mitotic arrest deficiency protein 2 (MAD2), is a centrally important mediator of the cellular response to paclitaxel. MAD2 immunohistochemical analysis was performed on 82 high-grade serous EOC samples. A multivariate Cox regression analysis of nuclear MAD2 IHC intensity adjusting for stage, tumour grade and optimum surgical debulking revealed that low MAD2 IHC staining intensity was significantly associated with reduced progression-free survival (PFS) (p = 0.0003), with a hazard ratio of 4.689. The in vitro analyses of five ovarian cancer cell lines demonstrated that cells with low MAD2 expression were less sensitive to paclitaxel. Furthermore, paclitaxel-induced activation of the spindle assembly checkpoint (SAC) and apoptotic cell death was abrogated in cells transfected with MAD2 siRNA. In silico analysis identified a miR-433 binding domain in the MAD2 3\\' UTR, which was verified in a series of experiments. Firstly, MAD2 protein expression levels were down-regulated in pre-miR-433 transfected A2780 cells. Secondly, pre-miR-433 suppressed the activity of a reporter construct containing the 3\\'-UTR of MAD2. Thirdly, blocking miR-433 binding to the MAD2 3\\' UTR protected MAD2 from miR-433 induced protein down-regulation. Importantly, reduced MAD2 protein expression in pre-miR-433-transfected A2780 cells rendered these cells less sensitive to paclitaxel. In conclusion, loss of MAD2 protein expression results in increased resistance to paclitaxel in EOC cells. Measuring MAD2 IHC staining intensity may predict

Hydroxyurea with or without imatinib in the treatment of recurrent or progressive meningiomas: a randomized phase II trial by Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO).

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Mazza, Elena; Brandes, Alba; Zanon, Silvia; Eoli, Marika; Lombardi, Giuseppe; Faedi, Marina; Franceschi, Enrico; Reni, Michele

2016-01-01

Hydroxyurea (HU) is among the most widely used salvage therapies in progressive meningiomas. Platelet-derived growth factor receptors are expressed in virtually all meningiomas. Imatinib sensitizes transformed cells to the cytotoxic effects of chemotherapeutic agents that interfere with DNA metabolism. The combination of HU with imatinib yielded intriguing results in recurrent malignant glioma. The current trial addressed the activity of this association against meningioma. Patients with recurrent or progressive WHO grade I-III meningioma, without therapeutic indication for surgery, radiotherapy, or stereotactic radiosurgery, aged 18-75 years, ECOG performance status 0-2, and not on enzyme-inducing anti-epileptic drugs were randomized to receive HU 500 mg BID ± imatinib 400 mg QD until progression, unacceptable toxicity, or patient's refusal. The primary endpoint was progression-free survival rate at 9 months (PFS-9). Between September 2009 and February 2012, 15 patients were randomized to receive HU + imatinib (N = 7; Arm A) or HU alone (N = 8; Arm B). Afterward the trial was prematurely closed due to slow enrollment rate. PFS-9 (A/B) was 0/75%, and median PFS was 4/19.5 months. Median and 2-year overall survival (A/B) rates were: 6/27.5 months; 28.5/75%, respectively. Main G3-4 toxicities were: G3 neutropenia in 1/0, G4 headache in 1/1, and G3 vomiting in 1/0. The conduction of a study in recurrent or progressive meningioma remains a challenge. Given the limited number of patients enrolled, no firm conclusions can be drawn about the combination of imatinib and HU. The optimal systemic therapy for meningioma failing surgery and radiation has yet to be identified.

Naturally acquired antibody responses to recombinant Pfs230 and Pfs48/45 transmission blocking vaccine candidates

NARCIS (Netherlands)

Jones, S; Grignard, L.; Nebie, I.; Chilongola, J.; Dodoo, D.; Sauerwein, R.W.; Theisen, M.; Roeffen, W.F.; Singh, S.K; Singh, R.K.; Kyei-Baafour, E.; Tetteh, K.; Drakeley, C.; Bousema, T.

2015-01-01

OBJECTIVES: Pfs48/45 and Pfs230 are Plasmodium falciparum sexual stage proteins and promising malaria transmission-blocking vaccine candidates. Antibody responses against these proteins may be naturally acquired and target antigens may be under selective pressure. This has consequences for the

Role of Intra-operative MRI (iMRI) in Improving Extent of Resection and Survival in Patients with Glioblastoma Multiforme.

Science.gov (United States)

Khan, Inamullah; Waqas, Muhammad; Shamim, Muhammad Shahzad

2017-07-01

Multiple intraoperative aids have been introduced to improve the extent of resection (EOR) in Glioblastoma Multiforme (GBM) patients, avoiding any new neurological deficits. Intraoperative MRI (iMRI) has been debated for its utility and cost for nearly two decades in neurosurgical literature. Review of literature suggests improved EOR in GBM patients who underwent iMRI assisted surgical resections leading to higher overall survival (OS) and progression free survival (PFS). iMRI provides real time intraoperative imaging with reasonable quality. Higher risk for new postoperative deficits with increased EOR is not reported in any study using iMRI. The level of evidence regarding prognostic benefits of iMRI is still of low quality..

Day 100 Peripheral Blood Absolute Lymphocyte/Monocyte Ratio and Survival in Classical Hodgkin's Lymphoma Postautologous Peripheral Blood Hematopoietic Stem Cell Transplantation

Directory of Open Access Journals (Sweden)

Luis F. Porrata

2013-01-01

Full Text Available Day 100 prognostic factors of postautologous peripheral blood hematopoietic stem cell transplantation (APBHSCT to predict clinical outcome in classical Hodgkin lymphoma (cHL patients have not been evaluated. Thus, we studied if the day 100 peripheral blood absolute lymphocyte/monocyte ratio (Day 100 ALC/AMC affects clinical outcomes by landmark analysis from day 100 post-APBHSCT. Only cHL patients achieving a complete remission at day 100 post-APBHSCT were studied. From 2000 to 2010, 131 cHL consecutive patients qualified for the study. The median followup from day 100 was 4.1 years (range: 0.2–12.3 years. Patients with a Day 100 ALC/AMC ≥ 1.3 experienced superior overall survival (OS and progression-free survival (PFS compared with Day 100 ALC/AMC < 1.3 (from day 100: OS, median not reached versus 2.8 years; 5 years OS rates of 93% (95% CI, 83%–97% versus 35% (95% CI, 19%–51%, resp., P<0.0001; from day 100: PFS, median not reached versus 1.2 years; 5 years PFS rates of 79% (95% CI, 69%–86% versus 27% (95% CI, 14%–45%, resp., P<0.0001. Day ALC/AMC ratio was an independent predictor for OS and PFS. Thus, Day 100 ALC/AMC ratio is a simple biomarker that can help to assess clinical outcomes from day 100 post-APBHSCT in cHL patients.

Enzalutamide in Men with Chemotherapy-naive Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study

NARCIS (Netherlands)

Beer, T.M.; Armstrong, A.J.; Rathkopf, D.; Loriot, Y.; Sternberg, C.N.; Higano, C.S.; Iversen, P.; Evans, C.P.; Kim, C.S.; Kimura, G.; Miller, K.; Saad, F.; Bjartell, A.S.; Borre, M.; Mulders, P.; Tammela, T.L.; Parli, T.; Sari, S.; Os, S. van; Theeuwes, A.; Tombal, B.

2017-01-01

Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naive metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the

Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer

DEFF Research Database (Denmark)

Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana

2017-01-01

Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated...

High RBM3 expression is associated with an improved survival and oxaliplatin response in patients with metastatic colorectal cancer.

Directory of Open Access Journals (Sweden)

Christina Siesing

Full Text Available High expression of the RNA-binding motif protein 3 (RBM3 has been shown to correlate, with prolonged survival in several malignant diseases and with the benefit of platinum-based chemotherapy in ovarian cancer. The aim of this study was to evaluate RBM3 in metastatic colorectal cancer (mCRC as a prognostic factor for overall survival and in relation to benefit of first-line chemotherapy.Immunohistochemical staining was conducted and evaluated in tumours from 455 mCRC patients. Kaplan-Meier analysis and Cox regression proportional hazards models were used to access the impact of RBM3 expression on overall survival (OS and progression-free survival (PFS.High RBM3 expression, both nuclear and cytoplasmic, was an independent prognostic factor for prolonged OS (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.50-0.90 and HR 0.66, 95% CI 0.48-0.91, respectively. PFS was significantly longer in patients with high RBM3 expression who had received first-line oxaliplatin based treatment, compared to those who had received irinotecan based treatment, both regarding nuclear and cytoplasmic expression (p-value 0.020 and 0.022 respectively.High RBM3 expression is an independent predictor of prolonged survival in mCRC patients, in particular in patients treated with first-line oxaliplatin based chemotherapy.

Survival effect of first- and second-line treatments for patients with primary glioblastoma: a cohort study from a prospective registry, 1997–2010

Science.gov (United States)

Nava, Francesca; Tramacere, Irene; Fittipaldo, Andrea; Bruzzone, Maria Grazia; DiMeco, Francesco; Fariselli, Laura; Finocchiaro, Gaetano; Pollo, Bianca; Salmaggi, Andrea; Silvani, Antonio; Farinotti, Mariangela; Filippini, Graziella

2014-01-01

Background Prospective follow-up studies of large cohorts of patients with glioblastoma (GBM) are needed to assess the effectiveness of conventional treatments in clinical practice. We report GBM survival data from the Brain Cancer Register of the Fondazione Istituto Neurologico Carlo Besta (INCB) in Milan, Italy, which collected longitudinal data for all consecutive patients with GBM from 1997 to 2010. Methods Survival data were obtained from 764 patients (aged>16 years) with histologically confirmed primary GBM who were diagnosed and treated over a 7-year period (2004–2010) with follow-up to April 2012 (cohort II). Equivalent data from 490 GBM patients diagnosed and treated over the preceding 7 years (1997–2003) with follow-up to April 2005 (cohort I) were available for comparison. Progression-free survival (PFS) was available from 361 and 219 patients actively followed up at INCB in cohorts II and I, respectively. Results Survival probabilities were 54% at 1 year, 21% at 2 years, and 11% at 3 years, respectively, in cohort II compared with 47%, 11%, and 5%, respectively, in cohort I. PFS was 22% and 12% at 1 year in cohorts II and I. Better survival and PFS in cohort II was significantly associated with introduction of the Stupp protocol into clinical practice, with adjusted hazard ratios (HRs) of 0.78 for survival and 0.73 for PFS, or a 22% relative decrease in the risk of death and a 27% relative decrease in the risk of recurrence. After recurrence, reoperation was performed in one-fifth of cohort I and in one-third of cohort II but was not effective (HR, 1.05 in cohort I and 1.02 in cohort II). Second-line chemotherapy, mainly consisting of nitrosourea-based chemotherapy, temozolomide, mitoxantrone, fotemustine, and bevacizumab, improved survival in both cohorts (HR, 0.57 in cohort I and 0.74 in cohort II). Radiosurgery was also effective (HR, 0.52 in cohort II). Conclusions We found a significant increase in overall survival, PFS, and survival after

Brachytherapy for stage IIIB squamous cell carcinoma of the uterine cervix: survival and toxicity

Energy Technology Data Exchange (ETDEWEB)

Zuliani, Antonio Carlos; Cunha, Maercio de Oliveira, E-mail: aczo.rt@gmail.co [Universidade Estadual de Campinas (UNICAMP), SP (Brazil); Esteves, Sergio C.B. [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Faculdade de Ciencias Medicas. Secao de Radioterapia; Teixeira, Julio Cesar [Universidade Estadual de Campinas (UNICAMP), SP (Brazil). Faculdade de Ciencias Medicas. Dept. de Tocoginecologia

2010-07-01

Objective: to compare survival and toxicity of three different treatments for stage IIIB cervix cancer: low-dose-rate (LDR), high-dose-rate (HDR) brachytherapy and association of HDR and chemotherapy. Methods: between 1985 and 2005, 230 patients with FIGO stage IIIB squamous cell carcinoma of the uterine cervix received 4-field pelvic teletherapy at doses between 40 and 50.4 Gy, with a different complementation in each group. The LDRB group, with 42 patients, received one or two insertions of LDR, with Cesium-137, in a total dose of 80 to 100Gy at point A. The HDR group, 155 patients received HDR in 4 weekly 7 Gy fractions and 9 Gy to 14.4 Gy applied to the involved parametria. The CHT group, 33 patients, were given the same treatment as the HDR group and received 5 or 6 weekly cycles of cisplatin, 40 mg per m2. Results: the five-year progression-free survival (PFS) was 60% for the HDR group and 45% for the LDR group, and the two-year PFS for the CHT group was 65% (p = 0.02). The five-year Overall Survival (OS) was 65% for the HDR group and 49% for the LDR group. The two-year OS was 86% for the CHT group (p 0.02). Rectum toxicity grade II was 7% for the LDR group, 4% for the HDR group and 7% for the CHT group that had one case of rectum toxicity grade IV. Conclusion: patients that received HDR had better OS and PFS. The Chemotherapy-HDR association showed no benefit when compared to HDR only. Toxicity rates showed no difference between the three groups. (author)

Pre-treatment inflammatory indexes as predictors of survival and cetuximab efficacy in metastatic colorectal cancer patients with wild-type RAS.

Science.gov (United States)

Yang, Jing; Guo, Xinli; Wang, Manni; Ma, Xuelei; Ye, Xiaoyang; Lin, Panpan

2017-12-07

This study aims at evaluating the prognostic significance of neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation indexes (SII) in metastatic colorectal cancer (mCRC) patients treated with cetuximab. Ninety-five patients receiving cetuximab for mCRC were categorized into the high or low NLR, PLR, LMR, and SII groups based on their median index values. Univariate and multivariate survival analysis were performed to identify the indexes' correlation with progression-free survival (PFS) and overall survival (OS). In the univariate analysis, ECOG performance status, neutrphil counts, lymphocyte counts, monocyte counts, NLR, PLR, and LDH were associated with survival. Multivariate analysis showed that ECOG performance status of 0 (hazard ratio [HR] 3.608, p < 0.001; HR 5.030, p < 0.001, respectively), high absolute neutrophil counts (HR 2.837, p < 0.001; HR 1.922, p = 0.026, respectively), low lymphocyte counts (HR 0.352, p < 0.001; HR 0.440, p = 0.001, respectively), elevated NLR (HR 3.837, p < 0.001; HR 2.467, p = 0.006) were independent predictors of shorter PFS and OS. In conclusion, pre-treatment inflammatory indexes, especially NLR were potential biomarkers to predict the survival of mCRC patients with cetuximab therapy.

Radiotherapy Alone is Associated with Improved Outcomes Over Surgery in the Management of Solitary Plasmacytoma.

Science.gov (United States)

Li, Qi-Wen; Niu, Shao-Qing; Wang, Han-Yu; Wen, Ge; Li, Yi-Yang; Xia, Yun-Fei; Zhang, Yu-Jing

2015-01-01

A moderate dose of radiation is the recommended treatment for solitary plasmacytoma (SP), but there is controversy over the role of surgery. Our study aimed at comparing different treatment modalities in the management of SP. Data from 38 consecutive patients with solitary plasmacytoma, including 16 with bone plasmacytoma and 22 with extramedullary plasmacytoma, were retrospectively reviewed. 15 patients received radiotherapy alone; 11 received surgery alone, and 12 received both. The median radiation dose was 50Gy. All operations were performed as radical resections. Local progression-free survival (LPFS), multiple myeloma-free survival (MMFS), progression-free survival (PFS) and overall survival (OS) were calculated and outcomes of different therapies were compared. The median follow-up time was 55 months. 5-year LPFS, MMFS, PFS and OS were 87.0%, 80.9%, 69.8% and 87.4%, respectively. Univariate analysis revealed, compared with surgery alone, radiotherapy alone was associated with significantly higher 5-year LPFS (100% vs 69.3%, p=0.016), MMFS (100% vs 51.4%, p=0.006), PFS (100% vs 33.7%, p=0.0004) and OS (100% vs 70%, p=0.041). Radiotherapy alone can be considered as a more effective treatment for SP over surgery. Whether a combination of radiotherapy and surgery improves outcomes requires further study.

Expression of the Hippo transducer TAZ in association with WNT pathway mutations impacts survival outcomes in advanced gastric cancer patients treated with first-line chemotherapy.

Science.gov (United States)

Melucci, Elisa; Casini, Beatrice; Ronchetti, Livia; Pizzuti, Laura; Sperati, Francesca; Pallocca, Matteo; De Nicola, Francesca; Goeman, Frauke; Gallo, Enzo; Amoreo, Carla Azzurra; Sergi, Domenico; Terrenato, Irene; Vici, Patrizia; Di Lauro, Luigi; Diodoro, Maria Grazia; Pescarmona, Edoardo; Barba, Maddalena; Mazzotta, Marco; Mottolese, Marcella; Fanciulli, Maurizio; Ciliberto, Gennaro; De Maria, Ruggero; Buglioni, Simonetta; Maugeri-Saccà, Marcello

2018-02-05

An extensive crosstalk co-regulates the Hippo and Wnt pathway. Preclinical studies revealed that the Hippo transducers YAP/TAZ mediate a number of oncogenic functions in gastric cancer (GC). Moreover, comprehensive characterization of GC demonstrated that the Wnt pathway is targeted by oncogenic mutations. On this ground, we hypothesized that YAP/TAZ- and Wnt-related biomarkers may predict clinical outcomes in GC patients treated with chemotherapy. In the present study, we included 86 patients with advanced GC treated with first-line chemotherapy in prospective phase II trials or in routine clinical practice. Tissue samples were immunostained to evaluate the expression of YAP/TAZ. Mutational status of key Wnt pathway genes (CTNNB1, APC and FBXW7) was assessed by targeted DNA next-generation sequencing (NGS). Survival curves were estimated and compared by the Kaplan-Meier product-limit method and the log-rank test, respectively. Variables potentially affecting progression-free survival (PFS) were verified in univariate Cox proportional hazard models. The final multivariate Cox models were obtained with variables testing significant at the univariate analysis, and by adjusting for all plausible predictors of the outcome of interest (PFS). We observed a significant association between TAZ expression and Wnt mutations (Chi-squared p = 0.008). Combined TAZ expression and Wnt mutations (TAZ pos /WNT mut ) was more frequently observed in patients with the shortest progression-free survival (negative outliers) (Fisher p = 0.021). Uni-and multivariate Cox regression analyses revealed that patients whose tumors harbored the TAZ pos /WNT mut signature had an increased risk of disease progression (univariate Cox: HR 2.27, 95% CI 1.27-4.05, p = 0.006; multivariate Cox: HR 2.73, 95% CI 1.41-5.29, p = 0.003). Finally, the TAZ pos /WNT mut signature negatively impacted overall survival. Collectively, our findings indicate that the oncogenic YAP/TAZ-Wnt crosstalk may be

Bortezomib, melphalan, prednisone (VMP) versus melphalan, prednisone, thalidomide (MPT) in elderly newly diagnosed multiple myeloma patients

DEFF Research Database (Denmark)

Morabito, Fortunato; Bringhen, Sara; Larocca, Alessandra

2014-01-01

Novel agents in combination with melphalan and prednisone (MP) significantly improved progression-free survival (PFS) and overall survival (OS) in multiple myeloma (MM). Randomized trials comparing MP plus bortezomib (VMP) versus MP plus thalidomide (MPT) are lacking. Nine hundred and fifty-six e...

Everolimus in advanced, progressive, well-differentiated, non-functional neuroendocrine tumors: RADIANT-4 lung subgroup analysis.

Science.gov (United States)

Fazio, Nicola; Buzzoni, Roberto; Delle Fave, Gianfranco; Tesselaar, Margot E; Wolin, Edward; Van Cutsem, Eric; Tomassetti, Paola; Strosberg, Jonathan; Voi, Maurizio; Bubuteishvili-Pacaud, Lida; Ridolfi, Antonia; Herbst, Fabian; Tomasek, Jiri; Singh, Simron; Pavel, Marianne; Kulke, Matthew H; Valle, Juan W; Yao, James C

2018-01-01

In the phase III RADIANT-4 study, everolimus improved median progression-free survival (PFS) by 7.1 months in patients with advanced, progressive, well-differentiated (grade 1 or grade 2), non-functional lung or gastrointestinal neuroendocrine tumors (NETs) vs placebo (hazard ratio, 0.48; 95% confidence interval [CI], 0.35-0.67; P < .00001). This exploratory analysis reports the outcomes of the subgroup of patients with lung NETs. In RADIANT-4, patients were randomized (2:1) to everolimus 10 mg/d or placebo, both with best supportive care. This is a post hoc analysis of the lung subgroup with PFS, by central radiology review, as the primary endpoint; secondary endpoints included objective response rate and safety measures. Ninety of the 302 patients enrolled in the study had primary lung NET (everolimus, n = 63; placebo, n = 27). Median PFS (95% CI) by central review was 9.2 (6.8-10.9) months in the everolimus arm vs 3.6 (1.9-5.1) months in the placebo arm (hazard ratio, 0.50; 95% CI, 0.28-0.88). More patients who received everolimus (58%) experienced tumor shrinkage compared with placebo (13%). Most frequently reported (≥5% incidence) grade 3-4 drug-related adverse events (everolimus vs. placebo) included stomatitis (11% vs. 0%), hyperglycemia (10% vs. 0%), and any infections (8% vs. 0%). In patients with advanced, progressive, well-differentiated, non-functional lung NET, treatment with everolimus was associated with a median PFS improvement of 5.6 months, with a safety profile similar to that of the overall RADIANT-4 cohort. These results support the use of everolimus in patients with advanced, non-functional lung NET. The trial is registered with ClinicalTrials.gov (no. NCT01524783). © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Retrospective Analysis of the Survival Benefit of Induction Chemotherapy in Stage IVa-b Nasopharyngeal Carcinoma.

Science.gov (United States)

Lan, Xiao-Wen; Zou, Xue-Bin; Xiao, Yao; Tang, Jie; OuYang, Pu-Yun; Su, Zhen; Xie, Fang-Yun

2016-01-01

The value of adding induction chemotherapy to chemoradiotherapy in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) remains controversial, yet high-risk patients with LA-NPC have poor outcomes after chemoradiotherapy. We aimed to assess the survival benefits of induction chemotherapy in stage IVa-b NPC. A total of 602 patients with stage IVa-b NPC treated with intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy with or without induction chemotherapy were retrospectively analyzed. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method, log-rank test and Cox regression analysis. In univariate analysis, 5-year OS was 83.2% for induction chemotherapy plus concurrent chemotherapy and 74.8% for concurrent chemotherapy alone, corresponding to an absolute risk reduction of 8.4% (P = 0.022). Compared to concurrent chemotherapy alone, addition of induction chemotherapy improved 5-year DMFS (83.2% vs. 74.4%, P = 0.018) but not 5-year LRFS (83.7% vs. 83.0%, P = 0.848) or PFS (71.9% vs. 66.0%, P = 0.12). Age, T category, N category, chemotherapy strategy and clinical stage were associated with 5-year OS (P = 0.017, P = 0.031, P = 0.007, P = 0.022, P = 0.001, respectively). In multivariate analysis, induction chemotherapy plus concurrent chemotherapy was an independent favorable prognostic factor for OS (HR, 0.62; 95% CI, 0.43-0.90, P = 0.012) and DMFS (HR, 0.57; 95% CI, 0.38-0.83, P = 0.004). In subgroup analysis, induction chemotherapy significantly improved 5-year DMFS in stage IVa (86.8% vs. 77.3%, P = 0.008), but provided no significant benefit in stage IVb. In patients with stage IVa-b NPC treated with IMRT, addition of induction chemotherapy to concurrent chemotherapy significantly improved 5-year OS and 5-year DMFS. This study provides a basis for selection of high risk patients in future clinical therapeutic

The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis.

Science.gov (United States)

Morgan, Gareth J; Gregory, Walter M; Davies, Faith E; Bell, Sue E; Szubert, Alexander J; Brown, Julia M; Coy, Nuria N; Cook, Gordon; Russell, Nigel H; Rudin, Claudius; Roddie, Huw; Drayson, Mark T; Owen, Roger G; Ross, Fiona M; Jackson, Graham H; Child, J Anthony

2012-01-05

Thalidomide maintenance has the potential to modulate residual multiple myeloma (MM) after an initial response. This trial compared the effect of thalidomide maintenance and no maintenance on progression-free survival (PFS) and overall survival (OS) in MM patients. After intensive or nonintensive induction therapy, 820 newly diagnosed MM patients were randomized to open-label thalidomide maintenance until progression, or no maintenance. Interphase FISH (iFISH) analysis was performed at study entry. Median PFS was significantly longer with thalidomide maintenance (log-rank P < .001). Median OS was similar between regimens (log-rank P = .40). Patients with favorable iFISH showed improved PFS (P = .004) and a trend toward a late survival benefit. Patients with adverse iFISH receiving thalidomide showed no significant PFS benefit and worse OS (P = .009). Effective relapse therapy enhanced survival after progression, translating into a significant OS benefit. Meta-analysis of this and other studies show a significant late OS benefit (P < .001, 7-year difference hazard ratio = 12.3; 95% confidence interval, 5.5-19.0). Thalidomide maintenance significantly improves PFS and can be associated with improved OS. iFISH testing is important in assessing the clinical impact of maintenance therapy. Overview analysis demonstrated that thalidomide maintenance was associated with a significant late OS benefit. This trial was registered at www.isrctn.org as #ISRCTN68454111.

Association between response rates and survival outcomes in patients with newly diagnosed multiple myeloma. A systematic review and meta-regression analysis.

Science.gov (United States)

Mainou, Maria; Madenidou, Anastasia-Vasiliki; Liakos, Aris; Paschos, Paschalis; Karagiannis, Thomas; Bekiari, Eleni; Vlachaki, Efthymia; Wang, Zhen; Murad, Mohammad Hassan; Kumar, Shaji; Tsapas, Apostolos

2017-06-01

We performed a systematic review and meta-regression analysis of randomized control trials to investigate the association between response to initial treatment and survival outcomes in patients with newly diagnosed multiple myeloma (MM). Response outcomes included complete response (CR) and the combined outcome of CR or very good partial response (VGPR), while survival outcomes were overall survival (OS) and progression-free survival (PFS). We used random-effect meta-regression models and conducted sensitivity analyses based on definition of CR and study quality. Seventy-two trials were included in the systematic review, 63 of which contributed data in meta-regression analyses. There was no association between OS and CR in patients without autologous stem cell transplant (ASCT) (regression coefficient: .02, 95% confidence interval [CI] -0.06, 0.10), in patients undergoing ASCT (-.11, 95% CI -0.44, 0.22) and in trials comparing ASCT with non-ASCT patients (.04, 95% CI -0.29, 0.38). Similarly, OS did not correlate with the combined metric of CR or VGPR, and no association was evident between response outcomes and PFS. Sensitivity analyses yielded similar results. This meta-regression analysis suggests that there is no association between conventional response outcomes and survival in patients with newly diagnosed MM. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Towards clinical development of a Pfs48/45-based transmission blocking malaria vaccine

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Theisen, Michael; Jore, Matthijs M; Sauerwein, Robert

2017-01-01

: PubMed was searched to review the progress and future prospects for clinical development of a Pfs48/45-based subunit vaccine. We will focus on biological function, naturally acquired immunity, functional activity of specific antibodies, sequence diversity, production of recombinant protein...

Risk factor assessment in high-risk, bacillus Calmette–Guérin-treated, non-muscle-invasive bladder cancer

Directory of Open Access Journals (Sweden)

Holz S

2017-09-01

Full Text Available Serge Holz,* Simone Albisinni,* Jacques Gilsoul, Michel Pirson, Véronique Duthie, Thierry Quackels, Marc Vanden Bossche, Thierry Roumeguère Department of Urology, Erasme Hospital, Université libre de Bruxelles, Belgium *These authors contributed equally to this work Objective: To assess the risk factors associated with recurrence, progression and survival in high-risk non-muscle-invasive bladder cancer (NMIBC patients treated with bacillus Calmette–Guérin (BCG and validate the European Organization for Research and Treatment of Cancer (EORTC and Spanish Urological Club for Oncological Treatment (CUETO scores.Patients and methods: We retrospectively analyzed all BCG-treated NMIBC patients from 1998 to 2012. Multiple variables were tested as risk factors for recurrence-free survival and progression-free survival (PFS. Variables included age, sex, grade, stage, tumor size, number of tumors, carcinoma in situ (CIS, recurrence status, BCG strain used, smoking status, use of re-staging transurethral resection and use of single immediate postoperative instillation. We also tested the accuracy of EORTC and CUETO scores in predicting recurrence and progression.Results: Overall, 123 patients were analyzed. Median (interquartile range follow-up was 49 months. The 5-year overall survival, cancer-specific survival, recurrence-free survival and PFS were 75.0%, 89.3%, 59.4% and 79.2%, respectively. On univariate analysis, multiple tumors (≥3, concomitant CIS and smoking influenced recurrence. Regarding progression, multiple tumors, concomitant CIS and Connaught strain (vs Tice negatively influenced PFS on univariate and multivariate analyses were independent prognostic factors. CUETO scores were accurate, with a slight overestimation, while EORTC score was not predictive of recurrence or progression.Conclusion: In this study, CIS and tumor multiplicity were unfavorable predictors of recurrence and progression in patients with NMIBC receiving BCG

Late Release of Circulating Endothelial Cells and Endothelial Progenitor Cells after Chemotherapy Predicts Response and Survival in Cancer Patients

Directory of Open Access Journals (Sweden)

Jeanine M. Roodhart

2010-01-01

Full Text Available We and others have previously demonstrated that the acute release of progenitor cells in response to chemotherapy actually reduces the efficacy of the chemotherapy. Here, we take these data further and investigate the clinical relevance of circulating endothelial (progenitor cells (CE(PCs and modulatory cytokines in patients after chemotherapy with relation to progression-free and overall survival (PFS/OS. Patients treated with various chemotherapeutics were included. Blood sampling was performed at baseline, 4 hours, and 7 and 21 days after chemotherapy. The mononuclear cell fraction was analyzed for CE(PC by FACS analysis. Plasma was analyzed for cytokines by ELISA or Luminex technique. CE(PCs were correlated with response and PFS/OS using Cox proportional hazard regression analysis. We measured CE(PCs and cytokines in 71 patients. Only patients treated with paclitaxel showed an immediate increase in endothelial progenitor cell 4 hours after start of treatment. These immediate changes did not correlate with response or survival. After 7 and 21 days of chemotherapy, a large and consistent increase in CE(PC was found (P < .01, independent of the type of chemotherapy. Changes in CE(PC levels at day 7 correlated with an increase in tumor volume after three cycles of chemotherapy and predicted PFS/OS, regardless of the tumor type or chemotherapy. These findings indicate that the late release of CE(PC is a common phenomenon after chemotherapeutic treatment. The correlation with a clinical response and survival provides further support for the biologic relevance of these cells in patients' prognosis and stresses their possible use as a therapeutic target.

Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment.

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Bonanno, Laura; Zago, Giulia; Marulli, Giuseppe; Del Bianco, Paola; Schiavon, Marco; Pasello, Giulia; Polo, Valentina; Canova, Fabio; Tonetto, Fabrizio; Loreggian, Lucio; Rea, Federico; Conte, PierFranco; Favaretto, Adolfo

2016-01-01

If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m(2), d1), and gemcitabine (1,000 mg/m(2) d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors-7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3-4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical-intent radiotherapy. The median PFS and OS were 11 months and 23 months, respectively. Both PFS and OS were significantly correlated to objective response (P<0.0001) and surgery (P<0.0001 and P=0.002). Patients obtaining PR and receiving local treatment achieved a median PFS and OS of 35 and 48 months, respectively. Median PFS and OS of patients not achieving PR or not receiving local treatment were 5-7 and 11-15 months, respectively. The extension of surgery did not affect the outcome. The multimodality treatment was feasible, and triple

Palbociclib Combined with Fulvestrant in Premenopausal Women with Advanced Breast Cancer and Prior Progression on Endocrine Therapy: PALOMA-3 Results.

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Loibl, Sibylle; Turner, Nicholas C; Ro, Jungsil; Cristofanilli, Massimo; Iwata, Hiroji; Im, Seock-Ah; Masuda, Norikazu; Loi, Sherene; André, Fabrice; Harbeck, Nadia; Verma, Sunil; Folkerd, Elizabeth; Puyana Theall, Kathy; Hoffman, Justin; Zhang, Ke; Bartlett, Cynthia Huang; Dowsett, Mitchell

2017-09-01

The efficacy and safety of palbociclib, a cyclin-dependent kinase 4/6 inhibitor, combined with fulvestrant and goserelin was assessed in premenopausal women with advanced breast cancer (ABC) who had progressed on prior endocrine therapy (ET). One hundred eight premenopausal endocrine-refractory women ≥18 years with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) ABC were among 521 women randomized 2:1 (347:174) to fulvestrant (500 mg) ± goserelin with either palbociclib (125 mg/day orally, 3 weeks on, 1 week off) or placebo. This analysis assessed whether the overall tolerable safety profile and significant progression-free survival (PFS) improvement extended to premenopausal women. Potential drug-drug interactions (DDIs) and ovarian suppression with goserelin were assessed via plasma pharmacokinetics and biochemical analyses, respectively. (ClinicalTrials.gov identifier: NCT01942135) RESULTS: Median PFS for premenopausal women in the palbociclib ( n  = 72) versus placebo arm ( n  = 36) was 9.5 versus 5.6 months, respectively (hazard ratio, 0.50, 95% confidence interval: 0.29-0.87), and consistent with the significant PFS improvement in the same arms for postmenopausal women. Any-grade and grade ≤3 neutropenia, leukopenia, and infections were among the most frequent adverse events reported in the palbociclib arm with concurrent goserelin administration. Hormone concentrations were similar between treatment arms and confirmed sustained ovarian suppression. Clinically relevant DDIs were not observed. Palbociclib combined with fulvestrant and goserelin was an effective and well-tolerated treatment for premenopausal women with prior endocrine-resistant HR+/HER2- ABC. Inclusion of both premenopausal and postmenopausal women in pivotal combination ET trials facilitates access to novel drugs for young women and should be considered as a new standard for clinical trial design. PALOMA-3, the first registrational

Antiproliferative effects of lanreotide autogel in patients with progressive, well-differentiated neuroendocrine tumours: a Spanish, multicentre, open-label, single arm phase II study

International Nuclear Information System (INIS)

Martín-Richard, Marta; Sala, Maria Angeles; Pericay, Carlos; Rivera, Fernando; Sastre, Javier; Segura, Ángel; Quindós, Maria; Maisonobe, Pascal; Massutí, Bartomeu; Pineda, Eva; Alonso, Vicente; Marmol, Maribel; Castellano, Daniel; Fonseca, Emilio; Galán, Antonio; Llanos, Marta

2013-01-01

Somatostatin analogues (SSAs) are indicated to relieve carcinoid syndrome but seem to have antiproliferative effects on neuroendocrine tumours (NETs). This is the first prospective study investigating tumour stabilisation with the long-acting SSA lanreotide Autogel in patients with progressive NETs. This was a multicentre, open-label, phase II trial conducted in 17 Spanish specialist centres. Patients with well-differentiated NETs and radiologically confirmed progression within the previous 6 months received lanreotide Autogel, 120 mg every 28 days over ≤92 weeks. The primary endpoint was progression-free survival (PFS). Secondary endpoints were response rate, tumour biomarkers, symptom control, quality of life (QoL), and safety. Radiographic imaging was assessed by a blinded central radiologist. Of 30 patients included in the efficacy and safety analyses, 40% had midgut tumours and 27% pancreatic tumours; 63% of tumours were functioning. Median PFS time was 12.9 (95% CI: 7.9, 16.5) months, and most patients achieved disease stabilisation (89%) or partial response (4%). No deterioration in QoL was observed. Nineteen patients (63%) experienced treatment-related adverse events, most frequently diarrhoea and asthenia; only one treatment-related adverse event (aerophagia) was severe. Lanreotide Autogel provided effective tumour stabilisation and PFS >12 months in patients with progressive NETs ineligible for surgery or chemotherapy, with a safety profile consistent with the pharmacology of the class. ClinicalTrials.gov Identifier http://clinicaltrials.gov/show/NCT00326469; EU Clinical Trial Register EudraCT no 2004-002871-18

Challenges in economic modeling of anticancer therapies: an example of modeling the survival benefit of olaparib maintenance therapy for patients with BRCA-mutated platinum-sensitive relapsed ovarian cancer.

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Hettle, Robert; Posnett, John; Borrill, John

2015-01-01

The aim of this paper is to describe a four health-state, semi-Markov model structure with health states defined by initiation of subsequent treatment, designed to make best possible use of the data available from a phase 2 clinical trial. The approach is illustrated using data from a sub-group of patients enrolled in a phase 2 clinical trial of olaparib maintenance therapy in patients with platinum-sensitive relapsed ovarian cancer and a BRCA mutation (NCT00753545). A semi-Markov model was developed with four health states: progression-free survival (PFS), first subsequent treatment (FST), second subsequent treatment (SST), and death. Transition probabilities were estimated by fitting survival curves to trial data for time from randomization to FST, time from FST to SST, and time from SST to death. Survival projections generated by the model are broadly consistent with the outcomes observed in the clinical trial. However, limitations of the trial data (small sample size, immaturity of the PFS and overall survival [OS] end-points, and treatment switching) create uncertainty in estimates of survival. The model framework offers a promising approach to evaluating cost-effectiveness of a maintenance therapy for patients with cancer, which may be generalizable to other chronic diseases.

Propensity Score–Matched Analysis of Comprehensive Local Therapy for Oligometastatic Non-Small Cell Lung Cancer That Did Not Progress After Front-Line Chemotherapy

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Sheu, Tommy [University of Texas School of Public Health, Houston, Texas (United States); Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Heymach, John V. [Department of Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Swisher, Stephen G. [Department of Thoracic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rao, Ganesh; Weinberg, Jeffrey S. [Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mehran, Reza [Department of Thoracic Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); McAleer, Mary Frances; Liao, Zhongxing [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Aloia, Thomas A. [Department of Gastrointestinal Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2014-11-15

Purpose: To retrospectively analyze factors influencing survival in patients with non-small cell lung cancer presenting with ≤3 synchronous metastatic lesions. Methods and Materials: We identified 90 patients presenting between 1998 and 2012 with non-small cell lung cancer and ≤3 metastatic lesions who had received at least 2 cycles of chemotherapy followed by surgery or radiation therapy before disease progression. The median number of chemotherapy cycles before comprehensive local therapy (CLT) (including concurrent chemoradiation as first-line therapy) was 6. Factors potentially affecting overall (OS) or progression-free survival (PFS) were evaluated with Cox proportional hazards regression. Propensity score matching was used to assess the efficacy of CLT. Results: Median follow-up time was 46.6 months. Benefits in OS (27.1 vs 13.1 months) and PFS (11.3 months vs 8.0 months) were found with CLT, and the differences were statistically significant when propensity score matching was used (P ≤ .01). On adjusted analysis, CLT had a statistically significant benefit in terms of OS (hazard ratio, 0.37; 95% confidence interval, 0.20-0.70; P ≤ .01) but not PFS (P=.10). In an adjusted subgroup analysis of patients receiving CLT, favorable performance status (hazard ratio, 0.43; 95% confidence interval, 0.22-0.84; P=.01) was found to predict improved OS. Conclusions: Comprehensive local therapy was associated with improved OS in an adjusted analysis and seemed to favorably influence OS and PFS when factors such as N status, number of metastatic lesions, and disease sites were controlled for with propensity score–matched analysis. Patients with favorable performance status had improved outcomes with CLT. Ultimately, prospective, randomized trials are needed to provide definitive evidence as to the optimal treatment approach for this patient population.

Propensity Score–Matched Analysis of Comprehensive Local Therapy for Oligometastatic Non-Small Cell Lung Cancer That Did Not Progress After Front-Line Chemotherapy

International Nuclear Information System (INIS)

Sheu, Tommy; Heymach, John V.; Swisher, Stephen G.; Rao, Ganesh; Weinberg, Jeffrey S.; Mehran, Reza; McAleer, Mary Frances; Liao, Zhongxing; Aloia, Thomas A.; Gomez, Daniel R.

2014-01-01

Purpose: To retrospectively analyze factors influencing survival in patients with non-small cell lung cancer presenting with ≤3 synchronous metastatic lesions. Methods and Materials: We identified 90 patients presenting between 1998 and 2012 with non-small cell lung cancer and ≤3 metastatic lesions who had received at least 2 cycles of chemotherapy followed by surgery or radiation therapy before disease progression. The median number of chemotherapy cycles before comprehensive local therapy (CLT) (including concurrent chemoradiation as first-line therapy) was 6. Factors potentially affecting overall (OS) or progression-free survival (PFS) were evaluated with Cox proportional hazards regression. Propensity score matching was used to assess the efficacy of CLT. Results: Median follow-up time was 46.6 months. Benefits in OS (27.1 vs 13.1 months) and PFS (11.3 months vs 8.0 months) were found with CLT, and the differences were statistically significant when propensity score matching was used (P ≤ .01). On adjusted analysis, CLT had a statistically significant benefit in terms of OS (hazard ratio, 0.37; 95% confidence interval, 0.20-0.70; P ≤ .01) but not PFS (P=.10). In an adjusted subgroup analysis of patients receiving CLT, favorable performance status (hazard ratio, 0.43; 95% confidence interval, 0.22-0.84; P=.01) was found to predict improved OS. Conclusions: Comprehensive local therapy was associated with improved OS in an adjusted analysis and seemed to favorably influence OS and PFS when factors such as N status, number of metastatic lesions, and disease sites were controlled for with propensity score–matched analysis. Patients with favorable performance status had improved outcomes with CLT. Ultimately, prospective, randomized trials are needed to provide definitive evidence as to the optimal treatment approach for this patient population

A Prospective Phase II Study of Cisplatin and Cremophor EL-Free Paclitaxel (Genexol-PM) in Patients with Unresectable Thymic Epithelial Tumors.

Science.gov (United States)

Kim, Hae Su; Lee, Ji Yun; Lim, Sung Hee; Sun, Jong-Mu; Lee, Se Hoon; Ahn, Jin Seok; Park, Keunchil; Moon, Seung Hwan; Ahn, Myung-Ju

2015-12-01

We conducted a prospective phase II study of cisplatin plus cremophor EL-free paclitaxel (Genexol-PM) in patients with unresectable thymic epithelial tumors to determine the efficacy and tolerability of the combination therapy. Patients were treated with cisplatin (70 mg/m) and Genexol-PM (230 mg/m) on day 1 of a 3-week cycle as first-line palliative chemotherapy. The primary end point of this study was objective response rate, and the secondary end points included toxicity, progression-free survival (PFS), overall survival, correlation between early 18F-fluorodeoxyglucose positron emission tomography/computed tomography response and PFS, and correlation between baseline flurododeoxyglucose uptake and histology. Forty-two patients with unresectable thymoma (n = 14) or thymic carcinoma (n = 28) were enrolled between May 2012 and October 2014. The median age was 59 years (range: 25-77) and 30 patients (71%) were male, and 39 patients (93%) had an ECOG PS of 1. The median number of treatment cycles was six (range: 1-6). For 40 assessable patients, the objective response rate was 62.5% (95% confidence interval [CI]: 47.6-77.4) with rates of 46% (95% CI: 23.3-76.9) for advanced thymoma (n = 13) and 70% (95% CI: 52.0-82.1) for thymic carcinoma (n = 27). With a median follow-up of 15.5 months, the median PFS for all 42 patients was 9.8 months (11.4 months for thymoma versus 8.1 months for thymic carcinoma). The 2-year overall survival was 77.9% for thymoma and 65.9% for thymic carcinoma. There were no treatment-related deaths. The most common grade 3 and 4 treatment-related adverse event was neutropenia in 11 patients (26%). Eight patients (19%) experienced grade 2 hypersensitivity reactions. There was no correlation between early positron emission tomography response and PFS, but tumor histology (thymoma versus thymic carcinoma) was correlated with SUVmax before chemotherapy. These data suggest that combination of cisplatin and Genexol-PM is highly effective and

Prostate Brachytherapy in Men ≥75 Years of Age

International Nuclear Information System (INIS)

Merrick, Gregory S.; Wallner, Kent E.; Galbreath, Robert W.; Butler, Wayne M.; Brammer, Sarah G.; Allen, Zachariah A.; Adamovich, Edward

2008-01-01

Purpose: To evaluate cause-specific survival (CSS), biochemical progression-free survival (bPFS), and overall survival (OS) in prostate cancer patients aged ≥75 years undergoing brachytherapy with or without supplemental therapies. Methods and Materials: Between April 1995 and August 2004, 145 consecutive patients aged ≥75 years underwent permanent prostate brachytherapy. Median follow-up was 5.8 years. Biochemical progression-free survival was defined by a prostate-specific antigen level ≤0.40 ng/mL after nadir. Patients with metastatic prostate cancer or hormone-refractory disease without obvious metastases who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause of death. Multiple clinical, treatment, and dosimetric parameters were evaluated for impact on survival. Results: Nine-year CSS, bPFS, and OS rates for the entire cohort were 99.3%, 97.1%, and 64.5%, respectively. None of the evaluated parameters predicted for CSS, whereas bPFS was most closely predicted by percentage positive biopsies. Overall survival and non-cancer deaths were best predicted by tobacco status. Thirty-seven patients have died, with 83.8% of the deaths due to cardiovascular disease (22 patients) or second malignancies (9 patients). To date, only 1 patient (0.7%) has died of metastatic prostate cancer. Conclusions: After brachytherapy, high rates of CSS and bPFS are noted in elderly prostate cancer patients. Overall, approximately 65% of patients are alive at 9 years, with survival most closely related to tobacco status. We believe our results support an aggressive locoregional approach in appropriately selected elderly patients

Policy Feedback System (PFS)

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Social Security Administration — The Policy Feedback System (PFS) is a web application developed by the Office of Disability Policy Management Information (ODPMI) team that gathers empirical data...

A critical prognostic analysis of neutrophil-lymphocyte ratio for patients undergoing nephroureterectomy due to upper urinary tract urothelial carcinoma.

Science.gov (United States)

Altan, Mesut; Haberal, Hakan Bahadır; Akdoğan, Bülent; Özen, Haluk

2017-10-01

To determine preoperative serum complete blood count parameters that affects survival of patients who underwent surgery for upper urinary tract urothelial cancer (UUT-UC). Since 1990, 150 patients underwent nephroureterectomy with bladder cuff excision for UUT-UC at Hacettepe University. Patients with a history of muscle-invasive bladder cancer, adjuvant chemotherapy or metastasis at the time of diagnosis were excluded. One hundred and thirteen patients without infective symptoms and with a full set of serum data were evaluated retrospectively. Effects of the neutrophil-lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet-lymphocyte ratio (PLR), and leukocyte count on disease-free survival (DFS) and progression-free survival (PFS) were investigated. Threshold values for each parameter to predict PFS were calculated. The mean age and median follow-up were 63.7 ± 11.1 years and 34 (3-186) months, respectively. Male to female ratio was 86/27. The 5-years PFS (bladder recurrence was excluded) and DFS were 59.6 and 38.4%, respectively. In multivariate analysis, NLR was independent prognostic factor for PFS and DFS (p = 0.006 and p = 0.021, respectively) while LMR was prognostic only for PFS (p = 0.037). For UUT-UC, NLR is a prognostic factor for PFS and DFS, while LMR is a prognostic indicator for PFS in present series.

Survival, hypothalamic obesity, and neuropsychological/psychosocial status after childhood-onset craniopharyngioma: newly reported long-term outcomes.

Science.gov (United States)

Sterkenburg, Anthe S; Hoffmann, Anika; Gebhardt, Ursel; Warmuth-Metz, Monika; Daubenbüchel, Anna M M; Müller, Hermann L

2015-07-01

Quality of life (QoL) and long-term prognosis are frequently, and often severely, impaired in craniopharyngioma (CP) patients. Knowledge of risk factors for long-term outcome is important for optimization of treatment. Overall survival (OS) and progression-free survival (PFS), body mass index (BMI), neuropsychological status (EORTCQLQ-C30, MFI-20), and psychosocial status were analyzed in 261 patients with childhood-onset CP diagnosed before 2000 and longitudinally observed in HIT-Endo. Twenty-year OS was lower (P = .006) in CP with hypothalamic involvement (HI) (n = 132; 0.84 ± 0.04) when compared with CP without HI (n = 82; 0.95 ± 0.04). OS was not related to degree of resection, sex, age at diagnosis, or year of diagnosis (before/after 1990). PFS (n = 168; 0.58 ± 0.05) was lower in younger patients (12 years of follow-up, patients with HI presented no further increase in BMI. QoL in CP patients with HI was impaired by obesity, physical fatigue, reduced motivation, dyspnea, diarrhea, and nonoptimal psychosocial development. OS and QoL are impaired by HI in long-term survivors of CP. HI is associated with severe obesity, which plateaus after 12 years. OS/PFS are not related to degree of resection, but gross-total resection should be avoided in cases of HI to prevent further hypothalamic damage, which exacerbates sequelae. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Risk factors and a prognostic score for survival after autologous stem-cell transplantation for relapsed or refractory Hodgkin lymphoma

DEFF Research Database (Denmark)

Bröckelmann, P J; Müller, H; Casasnovas, O

2017-01-01

study (n = 1045), precise and valid risk prognostication in HL patients undergoing ASCT can be achieved with five easily available clinical RFs. The proposed prognostic score hence allows reliable stratification of patients for innovative therapeutic approaches in clinical practice and future trials...... therapeutic approaches, we investigated a comprehensive set of risk factors (RFs) for survival after ASCT. Methods: In this multinational prognostic multivariable modeling study, 23 potential RFs were retrospectively evaluated in HL patients from nine prospective trials with multivariable Cox proportional...... of potential RFs had significant impact on progression-free survival (PFS) with hazard ratios (HR) ranging from 1.39 to 2.22. The multivariable analysis identified stage IV disease, time to relapse ≤3 months, ECOG performance status ≥1, bulk ≥5 cm and inadequate response to salvage chemotherapy [

Correlation of 18F-FDG PET and MRI Apparent Diffusion Coefficient Histogram Metrics with Survival in Diffuse Intrinsic Pontine Glioma: A Report from the Pediatric Brain Tumor Consortium.

Science.gov (United States)

Zukotynski, Katherine A; Vajapeyam, Sridhar; Fahey, Frederic H; Kocak, Mehmet; Brown, Douglas; Ricci, Kelsey I; Onar-Thomas, Arzu; Fouladi, Maryam; Poussaint, Tina Young

2017-08-01

The purpose of this study was to describe baseline 18 F-FDG PET voxel characteristics in pediatric diffuse intrinsic pontine glioma (DIPG) and to correlate these metrics with baseline MRI apparent diffusion coefficient (ADC) histogram metrics, progression-free survival (PFS), and overall survival. Methods: Baseline brain 18 F-FDG PET and MRI scans were obtained in 33 children from Pediatric Brain Tumor Consortium clinical DIPG trials. 18 F-FDG PET images, postgadolinium MR images, and ADC MR images were registered to baseline fluid attenuation inversion recovery MR images. Three-dimensional regions of interest on fluid attenuation inversion recovery MR images and postgadolinium MR images and 18 F-FDG PET and MR ADC histograms were generated. Metrics evaluated included peak number, skewness, and kurtosis. Correlation between PET and MR ADC histogram metrics was evaluated. PET pixel values within the region of interest for each tumor were plotted against MR ADC values. The association of these imaging markers with survival was described. Results: PET histograms were almost always unimodal (94%, vs. 6% bimodal). None of the PET histogram parameters (skewness or kurtosis) had a significant association with PFS, although a higher PET postgadolinium skewness tended toward a less favorable PFS (hazard ratio, 3.48; 95% confidence interval [CI], 0.75-16.28 [ P = 0.11]). There was a significant association between higher MR ADC postgadolinium skewness and shorter PFS (hazard ratio, 2.56; 95% CI, 1.11-5.91 [ P = 0.028]), and there was the suggestion that this also led to shorter overall survival (hazard ratio, 2.18; 95% CI, 0.95-5.04 [ P = 0.067]). Higher MR ADC postgadolinium kurtosis tended toward shorter PFS (hazard ratio, 1.30; 95% CI, 0.98-1.74 [ P = 0.073]). PET and MR ADC pixel values were negatively correlated using the Pearson correlation coefficient. Further, the level of PET and MR ADC correlation was significantly positively associated with PFS; tumors with higher

Perioperative blood transfusion: does it influence survival and cancer progression in metastatic spine tumor surgery?

Science.gov (United States)

Zaw, Aye Sandar; Kantharajanna, Shashidhar B; Maharajan, Karthikeyan; Tan, Barry; Vellayappan, Balamurugan; Kumar, Naresh

2017-02-01

Despite advances in surgical techniques for spinal metastases, there is often substantial blood loss, resulting in patients requiring blood transfusion during the perioperative period. Allogeneic blood transfusion (ABT) has been the main replenishment method for lost blood. However, the impact of ABT on cancer-related outcomes has been controversial in various studies. We aimed to evaluate the influence of perioperative ABT on disease progression and survival in patients undergoing metastatic spinal tumor surgery (MSTS). We conducted a retrospective study that included 247 patients who underwent MSTS at a single tertiary institution between 2005 and 2014. The impact of using perioperative ABT (either exposure to or quantities of transfusion) on disease progression and survival was assessed using Cox regression analyses while adjusting for potential confounding variables. Of 247 patients, 133 (54%) received ABT. The overall median number of blood units transfused was 2 (range, 0-10 units). Neither blood transfusion exposure nor quantities of transfusion were associated with overall survival (hazard ratio [HR], 1.15 [p = 0.35] and 1.10 [p = 0.11], respectively) and progression-free survival (HR, 0.87 [p = 0.18] and 0.98 [p = 0.11], respectively). The factors that influenced overall survival were primary tumor type and preoperative Eastern Cooperative Oncology Group performance status, whereas primary tumor type was the only factor that had an impact on progression-free survival. This is the first study providing evidence that disease progression and survival in patients who undergo MSTS are less likely to be influenced by perioperative ABT. The worst oncologic outcomes are more likely to be caused by the clinical circumstances necessitating blood transfusion, but not transfusion itself. However, because ABT can have a propensity toward developing postoperative infections, including surgical site infection, the use of patient blood management

High expression of insulin receptor on tumour-associated blood vessels in invasive bladder cancer predicts poor overall and progression-free survival.

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Roudnicky, Filip; Dieterich, Lothar C; Poyet, Cedric; Buser, Lorenz; Wild, Peter; Tang, Dave; Camenzind, Peter; Ho, Chien Hsien; Otto, Vivianne I; Detmar, Michael

2017-06-01

Bladder cancer is a frequently recurring disease with a very poor prognosis once progressed to invasive stages, and tumour-associated blood vessels play a crucial role in this process. In order to identify novel biomarkers associated with progression, we isolated blood vascular endothelial cells (BECs) from human invasive bladder cancers and matched normal bladder tissue, and found that tumour-associated BECs greatly up-regulated the expression of insulin receptor (INSR). High expression of INSR on BECs of invasive bladder cancers was significantly associated with shorter progression-free and overall survival. Furthermore, increased expression of the INSR ligand IGF-2 in invasive bladder cancers was associated with reduced overall survival. INSR may therefore represent a novel biomarker to predict cancer progression. Mechanistically, we observed pronounced hypoxia in human bladder cancer tissue, and found a positive correlation between the expression of the hypoxia marker gene GLUT1 and vascular INSR expression, indicating that hypoxia drives INSR expression in tumour-associated blood vessels. In line with this, exposure of cultured BECs and human bladder cancer cell lines to hypoxia led to increased expression of INSR and IGF-2, respectively, and IGF-2 increased BEC migration through the activation of INSR in vitro. Taken together, we identified vascular INSR expression as a potential biomarker for progression in bladder cancer. Furthermore, our data suggest that IGF-2/INSR mediated paracrine crosstalk between bladder cancer cells and endothelial cells is functionally involved in tumour angiogenesis and may thus represent a new therapeutic target. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The prognostic value of HPV combined p16 status in patients with anal squamous cell carcinoma: a meta-analysis.

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Sun, Guorui; Dong, Xiaoyuan; Tang, Xiaolong; Qu, Hui; Zhang, Hao; Zhao, Ensheng

2018-01-30

Human papillomavirus (HPV) DNA and p16 expression have been identified to be related to the progression of anal squamous cell carcinoma (ASCC). However, the prognostic relevance of combined detection, particularly HPV-/p16+ and HPV+/p16- signatures, is unknown. A meta-analysis of epidemiologic studies was therefore conducted to address this issue. Data were collected from studies comparing overall survival (OS) and disease-free survival (DFS) / disease-specific survival (DSS) / relapse-free survival (RFS) / progression-free survival (PFS) in ASCC patients with HPV and p16 status. The electronic databases of MEDLINE and EMBASE were searched from their inception till 31 May 2017. Study-specific risk estimates were pooled using a fixed-effects model for OS and DFS/DSS/RFS/PFS. Four studies involving a total of 398 ASCC cases were included in this meta-analysis. The pooled results showed that HPV+/p16+ cancers were significantly associated with improved OS (HR = 0.30, 95% CI: 0.17-0.51) and DFS/DSS/RFS/PFS (HR = 0.23, 95% CI: 0.14-0.36). However, patients with HPV-/p16+ or HPV+/p16- do not have a comparably good prognosis compared with HPV+/p16+ patients. The meta-analysis indicated that concomitant detection of HPV-DNA and p16 expression may be of prognostic or therapeutic utility in the evaluation of factors contributing to ASCC. Testing tumor specimens for HPV-DNA and p16 expression might indirectly affect treatment decisions.

Pretreatment Serum Testosterone and Androgen Deprivation: Effect on Disease Recurrence and Overall Survival in Prostate Cancer Patients Treated With Brachytherapy

International Nuclear Information System (INIS)

Taira, Al V.; Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Wallner, Kent E.; Allen, Zachariah A.; Lief, Jonathan H.; Adamovich, Edward

2009-01-01

Purpose: Low testosterone has been implicated as a possible adverse prognostic factor in patients with newly diagnosed prostate cancer. We evaluated the impact of pretreatment serum testosterone on survival after prostate brachytherapy. Methods and Materials: From October 2001 to November 2004, 619 patients underwent brachytherapy and 546 had a pretreatment serum testosterone level measured. Pretreatment serum testosterone levels were assigned by the following criteria: below-normal (n = 105), low normal (n = 246), mid normal (n = 132), high normal (n = 50), and above normal (n = 13). Median follow-up was 5.2 years. Cause of death was determined for each deceased patient. Results: Six-year biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were 97.7%, 99.8%, and 89.2%. When comparing patients with low or low normal testosterone with those with average or higher testosterone, there was no significant difference in bPFS (97.6% vs. 98.4%; p = 0.72), CSS (99.8% vs. 100%; p = 0.72), or OS (88.9% vs. 90.8%; p = 0.73). Among patients with average and higher pretreatment testosterone, there was no significant difference in outcomes when comparing patients who did and did not receive androgen deprivation therapy (ADT). For patients with low or low normal testosterone levels, there was no significant difference in bPFS or CSS when comparing patients who did and did not receive ADT. However, there was a trend toward lower OS in patients with baseline lower testosterone levels who also received ADT (83.9% vs. 91.3%, p = 0.075). Conclusions: Low pretreatment testosterone levels alone did not affect disease recurrence or OS. Patients with baseline low testosterone who also were treated with ADT had a trend toward decreased OS.

Association of single nucleotide polymorphisms in the MVP gene with platinum resistance and survival in patients with epithelial ovarian cancer.

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Zhao, Ya-Nan; He, Dong-Ning; Wang, Ya-DI; Li, Jun-Jie; Ha, Min-Wen

2016-04-01

The human major vault protein (MVP) has been linked to the development of multidrug resistance in cancer cells, and overexpression of MVP has been observed in ovarian cancer tissues. The aim of the present study was to investigate the association between single nucleotide polymorphisms (SNPs) in the MVP gene and the tumor response to platinum-based chemotherapy and survival of patients affected by epithelial ovarian cancer (EOC), in addition to confirm whether tetra-primer amplification-refractory mutation system (ARMS)-polymerase chain reaction (PCR) is an accurate genotyping method. For this purpose, two polymorphisms in the MVP gene, namely reference SNP (rs)1057451 and rs4788186, were selected from the data obtained by the International haplotype map (HapMap) Project regarding Chinese Han population, and were evaluated by tetra-primer ARMS-PCR. Upon validation by DNA sequencing, the association of these polymorphisms with platinum resistance, progression-free survival (PFS) and overall survival (OS) in patients with EOC was assessed. The results of tetra-primer ARMS-PCR were in agreement with those derived from DNA sequencing. No significant differences were observed between platinum-sensitive and platinum-resistant cohorts in terms of allele and genotype distribution of these two polymorphisms in the MVP gene, which were not associated with PFS or OS. However, a trend toward prolonged PFS was observed in patients carrying the heterozygous AG allele at the rs4788186 locus. These results suggest that rs1057451 and rs4788186 variants in the MVP gene are not associated with favorable therapeutic response to platinum or longer survival in Chinese Han patients affected by EOC. In addition, the data of the present study confirm that tetra-primer ARMS-PCR is a trustworthy and economical genotyping method.

Dynamic contrast-enhanced MRI, diffusion-weighted MRI and {sup 18}F-FDG PET/CT for the prediction of survival in oropharyngeal or hypopharyngeal squamous cell carcinoma treated with chemoradiation

Energy Technology Data Exchange (ETDEWEB)

Ng, Shu-Hang [Chang Gung University, Molecular Imaging Center, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung University, Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung University, Department of Medical Imaging and Radiological Sciences, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Liao, Chun-Ta [Chang Gung University, Department of Otorhinolaryngology, Head and Neck Surgery, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Lin, Chien-Yu; Chang, Joseph Tung-Chieh; Fan, Kang-Hsing [Chang Gung University, Department of Radiation Oncology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chan, Sheng-Chieh; Yen, Tzu-Chen [Chang Gung University, Molecular Imaging Center, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung University, Department of Nuclear Medicine, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Lin, Yu-Chun [Chang Gung University, Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung University, Department of Medical Imaging and Radiological Sciences, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Ko, Sheung-Fat [Chang Gung University, Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Wang, Hung-Ming [Chang Gung University, Department of Medical Oncology, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Yang, Lan-Yan [Chang Gung University, Biostatistics and Informatics Unit, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Wang, Jiun-Jie [Chang Gung University, Department of Medical Imaging and Radiological Sciences, Chang Gung Memorial Hospital, Kueishan, Taoyuan (China); Chang Gung Memorial Hospital, Neuroscience Research Center, Taoyuan (China); Chang Gung Memorial Hospital, Department of Diagnostic Radiology, Keelung (China); Chang Gung University / Chang Gung Memorial Hospital, Linkou, Medical Imaging Research Center, Institute for Radiological Research, Taoyuan (China)

2016-11-15

We prospectively investigated the roles of pretreatment dynamic contrast-enhanced MR imaging (DCE-MRI), diffusion-weighted MR imaging (DWI) and {sup 18}F-fluorodeoxyglucose-positron emission tomography ({sup 18}F-FDG PET)/CT for predicting survival of oropharyngeal or hypopharyngeal squamous cell carcinoma (OHSCC) patients treated with chemoradiation. Patients with histologically proven OHSCC and neck nodal metastases scheduled for chemoradiation were eligible. Clinical variables as well as DCE-MRI-, DWI- and {sup 18}F-FDG PET/CT-derived parameters of the primary tumours and metastatic neck nodes were analysed in relation to 3-year progression-free survival (PFS) and overall survival (OS) rates. Eighty-six patients were available for analysis. Multivariate analysis identified the efflux rate constant (K{sub ep})-tumour < 3.79 min{sup -1} (P = 0.001), relative volume of extracellular extravascular space (V{sub e})-node < 0.23 (P = 0.004) and SUV{sub max}-tumour > 19.44 (P = 0.025) as independent risk factors for both PFS and OS. A scoring system based upon the sum of each of the three imaging parameters allowed stratification of our patients into three groups (patients with 0/1 factor, patients with 2 factors and patients with 3 factors, respectively) with distinct PFS (3-year rates = 72 %, 38 % and 0 %, P < 0.0001) and OS (3-year rates = 81 %, 46 % and 20 %, P < 0.0001). K{sub ep}-tumour, V{sub e}-node and SUV{sub max}-tumour were independent prognosticators for OHSCC treated with chemoradiation. Their combination helped survival stratification. (orig.)

PFS: a distributed and customizable file system

NARCIS (Netherlands)

Bosch, H.G.P.; Mullender, Sape J.

1996-01-01

In this paper we present our ongoing work on the Pegasus File System (PFS), a distributed and customizable file system that can be used for off-line file system experiments and on-line file system storage. PFS is best described as an object-oriented component library from which either a true file

Comparison of long-term survival and toxicity of simultaneous integrated boost vs conventional fractionation with intensity-modulated radiotherapy for the treatment of nasopharyngeal carcinoma

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Tao HM

2016-03-01

Full Text Available Hengmin Tao,1,2 Yumei Wei,1 Wei Huang,1 Xiujuan Gai,1,2 Baosheng Li11Department of 6th Radiation Oncology, Shandong Cancer Hospital and Institute, 2School of Medicine and Life Sciences, Jinan University-Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaAim: In recent years, the intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB and intensity-modulated radiotherapy with conventional fractionation (IMRT-CF have been involved in the treatment of nasopharyngeal carcinoma (NPC. However, the potential clinical effects and toxicities are still controversial.Methods: Here, 107 patients with biopsy-proven locally advanced NPC between March 2004 and January 2011 were enrolled in the retrospective study. Among them, 54 patients received IMRT-SIB, and 53 patients received IMRT-CF. Subsequently, overall survival (OS, 5-year progression-free survival (PFS, 5-year locoregional recurrence-free survival (LRFS, and relevant toxicities were analyzed.Results: In the present study, all patients completed the treatment, and the overall median follow-up time was 80 months (range: 8–126 months. The 5-year OS analysis revealed no significant difference between the IMRT-SIB and IMRT-CF groups (80.9% vs 80.5%, P=0.568. In addition, there were also no significant between-group differences in 5-year PFS (73.3% vs 74.4%, P=0.773 and 5-year LRFS (88.1% vs 90.8%, P=0.903. Notably, the dose to critical organs (spinal cord, brainstem, and parotid gland in patients treated by IMRT-CF was significantly lower than that in patients treated by IMRT-SIB (all P<0.05.Conclusion: Both IMRT-SIB and IMRT-CF techniques are effective in treating locally advanced NPC, with similar OS, PFS, and LRFS. However, IMRT-CF has more advantages than IMRT-SIB in protecting spinal cord, brainstem, and parotid gland from acute and late toxicities, such as xerostomia. Further prospective study is warranted to confirm our findings.Keywords: intensity

Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma.

Science.gov (United States)

Facon, Thierry; Dimopoulos, Meletios A; Dispenzieri, Angela; Catalano, John V; Belch, Andrew; Cavo, Michele; Pinto, Antonello; Weisel, Katja; Ludwig, Heinz; Bahlis, Nizar J; Banos, Anne; Tiab, Mourad; Delforge, Michel; Cavenagh, Jamie D; Geraldes, Catarina; Lee, Je-Jung; Chen, Christine; Oriol, Albert; De La Rubia, Javier; White, Darrell; Binder, Daniel; Lu, Jin; Anderson, Kenneth C; Moreau, Philippe; Attal, Michel; Perrot, Aurore; Arnulf, Bertrand; Qiu, Lugui; Roussel, Murielle; Boyle, Eileen; Manier, Salomon; Mohty, Mohamad; Avet-Loiseau, Herve; Leleu, Xavier; Ervin-Haynes, Annette; Chen, Guang; Houck, Vanessa; Benboubker, Lotfi; Hulin, Cyrille

2018-01-18

This FIRST trial final analysis examined survival outcomes in patients with transplant-ineligible newly diagnosed multiple myeloma (NDMM) treated with lenalidomide and low-dose dexamethasone until disease progression (Rd continuous), Rd for 72 weeks (18 cycles; Rd18), or melphalan, prednisone, and thalidomide (MPT; 72 weeks). The primary endpoint was progression-free survival (PFS; primary comparison: Rd continuous vs MPT). Overall survival (OS) was a key secondary endpoint (final analysis prespecified ≥60 months' follow-up). Patients were randomized to Rd continuous (n = 535), Rd18 (n = 541), or MPT (n = 547). At a median follow-up of 67 months, PFS was significantly longer with Rd continuous vs MPT (hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.59-0.79; P < .00001) and was similarly extended vs Rd18. Median OS was 10 months longer with Rd continuous vs MPT (59.1 vs 49.1 months; HR, 0.78; 95% CI, 0.67-0.92; P = .0023), and similar with Rd18 (62.3 months). In patients achieving complete or very good partial responses, Rd continuous had an ≈30-month longer median time to next treatment vs Rd18 (69.5 vs 39.9 months). Over half of all patients who received second-line treatment were given a bortezomib-based therapy. Second-line outcomes were improved in patients receiving bortezomib after Rd continuous and Rd18 vs after MPT. No new safety concerns, including risk for secondary malignancies, were observed. Treatment with Rd continuous significantly improved survival outcomes vs MPT, supporting Rd continuous as a standard of care for patients with transplant-ineligible NDMM. This trial was registered at www.clinicaltrials.gov as #NCT00689936 and EudraCT as 2007-004823-39. © 2018 by The American Society of Hematology.

Survival with AGS-003, an autologous dendritic cell-based immunotherapy, in combination with sunitinib in unfavorable risk patients with advanced renal cell carcinoma (RCC): Phase 2 study results.

Science.gov (United States)

Amin, Asim; Dudek, Arkadiusz Z; Logan, Theodore F; Lance, Raymond S; Holzbeierlein, Jeffrey M; Knox, Jennifer J; Master, Viraj A; Pal, Sumanta K; Miller, Wilson H; Karsh, Lawrence I; Tcherepanova, Irina Y; DeBenedette, Mark A; Williams, W Lee; Plessinger, Douglas C; Nicolette, Charles A; Figlin, Robert A

2015-01-01

AGS-003 is an autologous immunotherapy prepared from fully matured and optimized monocyte-derived dendritic cells, which are co-electroporated with amplified tumor RNA plus synthetic CD40L RNA. AGS-003 was evaluated in combination with sunitinib in an open label phase 2 study in intermediate and poor risk, treatment naïve patients with metastatic clear cell renal cell carcinoma (mRCC). Twenty-one intermediate and poor risk patients were treated continuously with sunitinib (4 weeks on, 2 weeks off per 6 week cycle). After completion of the first cycle of sunitinib, patients were treated with AGS-003 every 3 weeks for 5 doses, then every 12 weeks until progression or end of study. The primary endpoint was to determine the complete response rate. Secondary endpoints included clinical benefit, safety, progression free survival (PFS) and overall survival (OS). Immunologic response was also monitored. Thirteen patients (62%) experienced clinical benefit (9 partial responses, 4 with stable disease); however there were no complete responses in this group of intermediate and poor risk mRCC patients and enrollment was terminated early. Median PFS from registration was 11.2 months (95% CI 6.0, 19.4) and the median OS from registration was 30.2 months (95% CI 9.4, 57.1) for all patients. Seven (33%) patients survived for at least 4.5 years, while five (24%) survived for more than 5 years, including 2 patients who remain progression-free with durable responses for more than 5 years at the time of this report. AGS-003 was well tolerated with only mild injection-site reactions. The most common adverse events were related to expected toxicity from sunitinib therapy. In patients who had sequential samples available for immune monitoring, the magnitude of the increase in the absolute number of CD8(+) CD28(+) CD45RA(-) effector/memory T cells (CTLs) after 5 doses of AGS-003 relative to baseline, correlated with overall survival. AGS-003 in combination with sunitinib was

SAMSN1 is highly expressed and associated with a poor survival in glioblastoma multiforme.

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Yong Yan

Full Text Available OBJECTIVES: To study the expression pattern and prognostic significance of SAMSN1 in glioma. METHODS: Affymetrix and Arrystar gene microarray data in the setting of glioma was analyzed to preliminarily study the expression pattern of SAMSN1 in glioma tissues, and Hieratical clustering of gene microarray data was performed to filter out genes that have prognostic value in malignant glioma. Survival analysis by Kaplan-Meier estimates stratified by SAMSN1 expression was then made based on the data of more than 500 GBM cases provided by The Cancer Genome Atlas (TCGA project. At last, we detected the expression of SAMSN1 in large numbers of glioma and normal brain tissue samples using Tissue Microarray (TMA. Survival analysis by Kaplan-Meier estimates in each grade of glioma was stratified by SAMSN1 expression. Multivariate survival analysis was made by Cox proportional hazards regression models in corresponding groups of glioma. RESULTS: With the expression data of SAMSN1 and 68 other genes, high-grade glioma could be classified into two groups with clearly different prognoses. Gene and large sample tissue microarrays showed high expression of SAMSN1 in glioma particularly in GBM. Survival analysis based on the TCGA GBM data matrix and TMA multi-grade glioma dataset found that SAMSN1 expression was closely related to the prognosis of GBM, either PFS or OS (P<0.05. Multivariate survival analysis with Cox proportional hazards regression models confirmed that high expression of SAMSN1 was a strong risk factor for PFS and OS of GBM patients. CONCLUSION: SAMSN1 is over-expressed in glioma as compared with that found in normal brains, especially in GBM. High expression of SAMSN1 is a significant risk factor for the progression free and overall survival of GBM.

The Predictive Value of Interim and Final [18F] Fluorodeoxyglucose Positron Emission Tomography after Rituximab-Chemotherapy in the Treatment of Non-Hodgkin's Lymphoma: A Meta-Analysis

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Yuyuan Zhu

2013-01-01

Full Text Available Background and Purpose. The aim of this study is to determine the prognostic value of interim and final FDG-PET in major histotypes of B-cell NHL patients treated with rituximab containing-chemotherapy. Methods. We searched for articles published in English, limited to lymphoma, rituximab, and FDG-PET, and dedicated to deal with the impact on progression and survival. The log hazard ratios (HR and their variances were estimated. Results. A PubMed and Scopus review of published trials identified 13 studies of Progression-free survival (PFS and overall survival (OS which were set as the main outcome measures. The combined HRs of I-PET for PFS and OS in DLBCL were 4.4 (P=0.11 and 3.99 (P=0.46, respectively. The combined HRs of F-PET for PFS and OS in DLBCL were 5.91 (P=0.39 and 6.75 (P=0.92, respectively. Regarding to non-DLBCL with F-PET, the combined HRs of F-PET for PFS and OS were 4.05 (P=0.79 and 5.1 (P=0.51, respectively. No publication bias existed. Conclusion. In DLBCL, both I-PET and F-PET can be performed for survival and progression analysis. But in other B-cell subtypes such as follicular lymphoma (FL and mantle cell lymphoma (MCL, it would be necessary to perform F-PET for predictive purposes.

Rituximab-containing reduced-intensity conditioning improves progression-free survival following allogeneic transplantation in B cell non-Hodgkin lymphoma

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Narendranath Epperla

2017-06-01

Full Text Available Abstract Background In B cell non-Hodgkin lymphoma (B-NHL, rituximab-containing reduced-intensity conditioning regimens (R-RIC have been shown to provide favorable outcomes in single-arm studies; however, large multicenter studies comparing R-RIC and non-rituximab-containing reduced-intensity conditioning regimens (nonR-RIC have not been performed. Using the CIBMTR database, we report the outcomes of R-RIC versus nonR-RIC regimens in B-NHL. Methods We evaluated 1401 adult B-NHL patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT who received nonR-RIC (n = 1022 or R-RIC (n = 379 regimens. Graft-versus-host disease (GVHD prophylaxis was limited to calcineurin inhibitor-based approaches. Results Median follow-up of survivors in the R-RIC and nonR-RIC groups was 47 and 37 months, respectively. On multivariate analysis, no difference was seen between the R-RIC and nonR-RIC cohorts in terms of acute GVHD grade II–IV (RR = 1.14, 95%CI = 0.83–1.56, p = 0.43 or grade III–IV (RR = 1.16, 95%CI = 0.72–1.89, p = 0.54, chronic GVHD (RR = 1.15, 95%CI = 0.92–1.46, p = 0.22, non-relapse mortality (RR = 0.90; 95%CI = 0.67–1.22; p = 0.51, relapse/progression (RR = 0.79; 95%CI = 0.63–1.01; p = 0.055, and mortality (RR = 0.84, 95%CI = 0.69–1.02, p = 0.08 risk. However, R-RIC was associated with a significantly improved progression-free survival (RR = 0.76; 95%CI 0.62–0.92; p = 0.006. On subgroup analysis, mortality benefit was noted in the R-RIC group patients not receiving busulfan-based RIC (RR = 0.76; 95%CI = 0.60–0.96; p = 0.02 and with the use of a higher cumulative rituximab dose (RR = 0.43; 95%CI = 0.21–0.90; p = 0.02. Conclusion Our analysis shows that inclusion of rituximab in RIC regimens improves progression-free survival in patients with B cell NHL. These data supports the use of R-RIC in B

Change in Neutrophil-to-lymphocyte Ratio in Response to Targeted Therapy for Metastatic Renal Cell Carcinoma as a Prognosticator and Biomarker of Efficacy

DEFF Research Database (Denmark)

Templeton, Arnoud J; Knox, Jennifer J; Lin, Xun

2016-01-01

at baseline and 6 (± 2) wk later. A landmark analysis at 8 wk was conducted to explore the prognostic value of relative NLR change on overall survival (OS), progression-free survival (PFS), and objective response rate using Cox or logistic regression models, adjusted for variables in IMDC score and NLR values...

Sunitinib-associated hypertension and neutropenia as efficacy biomarkers in metastatic renal cell carcinoma patients

DEFF Research Database (Denmark)

Donskov, Frede; Michaelson, M Dror; Puzanov, Igor

2015-01-01

), neutropenia (grade ⩾2), thrombocytopenia (grade ⩾2), hand-foot syndrome (grade >0), and asthenia/fatigue (grade >0)) were analysed in multivariate analyses of progression-free survival (PFS) and overall survival (OS) end points. RESULTS: On-treatment neutropenia and hypertension were associated with longer...... PFS (P=0.0276 and Pneutropenia was significantly associated...... with longer PFS and OS (P=0.013 and P=0.0122, respectively) and hypertension or hand-foot syndrome with longer OS (P=0.0036 and P=0.0218, respectively). The concordance index was 0.65 (95% CI: 0.63-0.67) for IMDC classification alone and 0.72 (95% CI: 0.70-0.74) when combined with hypertension and neutropenia...

Potential prolongation of PFS in mantle cell lymphoma after R-HyperCVAD: auto-SCT consolidation or rituximab maintenance.

Science.gov (United States)

Ahmadi, T; McQuade, J; Porter, D; Frey, N; Loren, A W; Goldstein, S C; Svoboda, J; Stadtmauer, E; Schuster, S J; Nasta, S D

2012-08-01

We retrospectively analyzed 44 patients undergoing first-line treatment for mantle cell lymphoma with R-HyperCVAD, with or without rituximab (R) maintenance or auto-SCT. The primary study end point was PFS; secondary end point was overall survival.Median follow up for all patients was 3.3 years. Median age was 54 years, and 95% (n=42) were stage III or IV at diagnosis. In all, 17 patients underwent consolidative auto-SCT and 12 patients received R maintenance. The overall response rate was 95%, with 91% achieving complete response (CR). Median PFS for all patients was 3.5 years. Median PFS was 2.3 years for patients treated with R-HyperCVAD alone vs 3.9 years (P=0.02) with R-HyperCVAD+ R maintenance and 4.5 years (P=0.01) with R-HyperCVAD+ auto-SCT. For patients who did not achieve CR at interim staging, PFS for R-HyperCVAD alone was 1.4 years vs not reached for R-HyperCVAD+ consolidation (either R maintenance or auto-SCT) (P=0.02). PFS for patients with CR at interim staging was 3.3 years vs not reached (P=0.04) after consolidation. Our data suggest potential improvement in PFS when R-HyperCVAD is consolidated with either R maintenance or auto-SCT. This benefit appears particularly significant in those patients who do not achieve CR at interim restaging.

The prevalence of PFS and prevalence and characteristics of reported food allergy; a survey of UK adults aged 18-75 incorporating a validated PFS diagnostic questionnaire.

Science.gov (United States)

Skypala, I J; Bull, S; Deegan, K; Gruffydd-Jones, K; Holmes, S; Small, I; Emery, P W; Durham, S R

2013-08-01

Pollen-food syndrome (PFS), a food allergy affecting pollen-sensitized individuals, is likely to be the most prevalent food allergy in adults, estimated to affect 50-90% of people allergic to birch tree pollen. A validated PFS diagnostic questionnaire (PFSDQ2) was used to determine the prevalence of PFS and also to characterize those who report reactions to foods. Five UK General practices each sent the PFSDQ2 by post to 2000 patients aged 18-75 years randomly selected from their practice database. The validated questionnaire was accompanied by an additional set of questions to ascertain the demographic of the population, the foods involved and the age of onset. There were 3590 subjects who returned completed questionnaires, with an average return rate from each practice of 36% (range 22-47%). Of these, 73 were diagnosed with PFS according to the questionnaire (PFS+ve) giving a population prevalence of 2%. A further 482 subjects reported reactions to foods but did not fulfil the diagnostic criteria for PFS. The greatest prevalence of PFS was in the Croydon (SE England) urban practice (4.1%) and the lowest in the Aberdeen (Scotland) urban practice (0.8%) (P < 0.001).The most frequently reported trigger foods were apples, hazelnuts and kiwifruit and the majority of those with PFS first experienced symptoms below the age of 20 years. PFS+ve subjects were also more likely to be female and have a higher socio-economic status than those who did not report reactions to foods. The UK prevalence of PFS was 2%, although this varied according to the location of the practice population. The majority of PFS+ve subjects first reported symptoms in their teens. The reported age of onset has important implications for the diagnosis of primary and cross-reactive peanut and tree nut allergies in teenagers and young adults. The continuing rise in aeroallergen sensitization is likely to result in an increased frequency of PFS presenting in both primary and secondary care. © 2013

Radioembolisation for liver metastases: results from a prospective 151 patient multi-institutional phase II study.

Science.gov (United States)

Benson, Al B; Geschwind, Jean-Francois; Mulcahy, Mary F; Rilling, William; Siskin, Gary; Wiseman, Greg; Cunningham, James; Houghton, Bonny; Ross, Mason; Memon, Khairuddin; Andrews, James; Fleming, Chad J; Herman, Joseph; Nimeiri, Halla; Lewandowski, Robert J; Salem, Riad

2013-10-01

To investigate the safety, response rate, progression-free and overall survival of patients with liver metastases treated with (90)Y (glass) radioembolisation in a prospective, multicenter phase II study. 151 patients with liver metastases (colorectal n=61, neuroendocrine n=43 and other tumour types n=47) refractory to standard of care therapies were enrolled in this prospective, multicenter, phase II study under an investigational device exemption. Clinical/laboratory/imaging follow-up were obtained at 30 days followed by 3-month intervals for 1 year and every 6 months thereafter. The primary end-point was progression-free survival (PFS); secondary end-points included safety, hepatic progression-free survival (HPFS), response rate and overall survival. Median age was 66 (range 25-88). Grade 3/4 adverse events included pain (12.8%), elevated alkaline phospatase (8.1%), hyperbilirubinemia (5.3%), lymphopaenia (4.1%), ascites (3.4%) and vomiting (3.4%). Treatment parameters including dose delivery were reproducible among centers. Disease control rates were 59%, 93% and 63% for colorectal, neuroendocrine and other primaries, respectively. Median PFS was 2.9 and 2.8 months for colorectal and other primaries, respectively. PFS was not achieved in the neuroendocrine group. Median survival from (90)Y treatment was 8.8 months for colorectal and 10.4 months for other primaries. Median survival for neuroendocrine patients has not been reached. Patients with liver metastases can be safely treated with (90)Y microspheres. This study is the first to demonstrate technical and dose reproducibility of (90)Y glass microspheres between centers in a prospective setting. Based on these promising data, three international, multicenter, randomised phase III studies in colorectal and hepatocellular carcinoma have been initiated. Copyright © 2013 Elsevier Ltd. All rights reserved.

Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer

NARCIS (Netherlands)

Peeters, Marc; Price, Timothy Jay; Cervantes, Andrés; Sobrero, Alberto F.; Ducreux, Michel; Hotko, Yevhen; André, Thierry; Chan, Emily; Lordick, Florian; Punt, Cornelis J. A.; Strickland, Andrew H.; Wilson, Gregory; Ciuleanu, Tudor-Eliade; Roman, Laslo; van Cutsem, Eric; Tzekova, Valentina; Collins, Simon; Oliner, Kelly S.; Rong, Alan; Gansert, Jennifer

2010-01-01

Panitumumab is a fully human anti-epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS) in chemotherapy-refractory metastatic colorectal cancer (mCRC). This trial evaluated the efficacy and safety of panitumumab plus fluorouracil, leucovorin, and

BRAF mutation and anaplasia may be predictive factors of progression-free survival in adult pleomorphic xanthoastrocytoma.

Science.gov (United States)

Tabouret, E; Bequet, C; Denicolaï, E; Barrié, M; Nanni, I; Metellus, P; Dufour, Henri; Chinot, O; Figarella-Branger, D

2015-12-01

Pleomorphic xanthoastrocytoma (PXA) is a rare, low-grade glioma that frequently occurs in pediatric patients. To analyze adult patients diagnosed with PXA and to search for pathological and molecular markers of diagnosis and prognosis. We retrospectively included patients older than 16 years with PXA who were referred to our institution between October 2003 and September 2013. All pathological diagnoses were reviewed by a neuropathologist. Histological characteristics and immunostaining of GFAP, OLIG2, neurofilament, CD34, Ki67, p53, p16, and IDH1 R132H were analyzed. The following molecular alterations were analyzed: mutations of IDH1/2, BRAF and the histone H3.3 and the EGFR amplification. Clinical data, treatment modalities, and patient outcome were recorded. We identified 16 adult patients with reviewed PXA diagnosis. No IDH neither histone H3.3 mutations were found; BRAF V600E mutation was recorded in six patients. Ten patients presented with anaplastic features. BRAF mutations were associated with lower Ki67, OLIG2 expression, and lack of p16 expression. Median PFS and OS were 41.5 months (95% CI: 11.4-71.6) and 71.4 months (95% CI: 15.5-127.3), respectively. BRAF mutation tended to be associated with greater PFS (p = 0.051), whereas anaplastic features were associated with minimal PFS (p = 0.042). PXA in adults PXA may present features distinct from pediatric PXA. Anaplastic features and BRAF mutation may potentially identify specific subgroups with distinct prognoses. Copyright © 2015 Elsevier Ltd. All rights reserved.

Low-dose fractionated radiotherapy and concomitant chemotherapy for recurrent or progressive glioblastoma. Final report of a pilot study

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Balducci, M.; Diletto, B.; Chiesa, S.; D' Agostino, G.R.; Gambacorta, M.A.; Ferro, M.; Valentini, V. [Catholic University of the Sacred Heart, Department of Radiation Oncology, Rome (Italy); Colosimo, C. [Catholic University of the Sacred Heart, Department of Radiology, Rome (Italy); Maira, G.; Anile, C. [Catholic University of the Sacred Heart, Department of Neurosurgery, Rome (Italy)

2014-04-15

Evaluated in this study were the feasibility and the efficacy of concurrent low dose fractionated radiotherapy (LD-FRT) and chemotherapy as palliative treatment for recurrent/progressive glioblastoma multiforme (GBM). Eligible patients had recurrent or progressive GBM, Karnofsky performance status ≥70, prior surgery, and standard radiochemotherapy treatment. Recurrence/progression disease during temozolomide (TMZ) received cisplatin (CDDP; 30 mg/m{sup 2} on days 1, 8, 15), fotemustine (FTM; 40 mg/m{sup 2} on days 2, 9, 16), and concurrent LD-FRT (0.3 Gy twice daily); recurrence/progression after 4 months from the end of adjuvant TMZ were treated by TMZ (150/200 mg/m{sup 2} on days 1-5) concomitant with LD-FRT (0.4 Gy twice daily). Primary endpoints were safety and toxicity. A total of 32 patients were enrolled. Hematologic toxicity G1-2 was observed in 18.7% of patients and G3-4 in 9.4%. One patient (3.1%) had complete response, 3 (9.4%) had partial response, 8 (25%) had stable disease for at least 8 weeks, while 20 patients (62.5%) experienced progressive disease. The clinical benefit was 37.5%. Median progression-free survival (PFS) and overall survival (OS) were 5 and 8 months, respectively. Survival rate at 12 months was of 27.8%. LD-FRT and chemotherapy for recurrent/progressive GBM have a good toxicity profile and clinical outcomes, even though further investigation of this novel palliative treatment approach is warranted. (orig.)

Treatment with Antiangiogenic Drugs in Multiple Lines in Patients with Metastatic Colorectal Cancer: Meta-Analysis of Randomized Trials

Directory of Open Access Journals (Sweden)

R.-D. Hofheinz

2016-01-01

Full Text Available Background. In metastatic colorectal cancer (mCRC, continuing antiangiogenic drugs beyond progression might provide clinical benefit. We synthesized the available evidence in a meta-analysis. Patients and Methods. We conducted a meta-analysis of studies investigating the use of antiangiogenic drugs beyond progression. Eligible studies were randomized phase II/III trials. Primary endpoints were overall survival (OS and progression-free survival (PFS. Secondary endpoints were the impact of continuing antiangiogenic drugs (i in subgroups, (ii in different types of compounds targeting the VEGF-axis (monoclonal antibodies versus tyrosine kinase inhibitors, and (iii on remission rates and prevention of progression. Results. Eight studies (3,668 patients were included. Continuing antiangiogenic treatment beyond progression significantly improved PFS (HR 0.64; 95%-CI, 0.55–0.75 and OS (HR 0.83; 95%-CI, 0.76–0.89. PFS was significantly improved in all subgroups with comparable HR. OS was improved in all subgroups stratified by age, gender, and ECOG status. The rate of patients achieving at least stable disease was improved with an OR of 2.25 (95%-CI, 1.41–3.58. Conclusions. This analysis shows a significant PFS and OS benefit as well as a benefit regarding disease stabilization when using antiangiogenic drugs beyond progression in mCRC. Future studies should focus on the optimal sequence of administering antiangiogenic drugs.

Algae-Produced Pfs25 Elicits Antibodies That Inhibit Malaria Transmission

Science.gov (United States)

Gregory, James A.; Li, Fengwu; Tomosada, Lauren M.; Cox, Chesa J.; Topol, Aaron B.; Vinetz, Joseph M.; Mayfield, Stephen

2012-01-01

Subunit vaccines are significantly more expensive to produce than traditional vaccines because they are based primarily on recombinant proteins that must be purified from the expression system. Despite the increased cost, subunit vaccines are being developed because they are safe, effective, and can elicit antibodies that confer protection against diseases that are not currently vaccine-preventable. Algae are an attractive platform for producing subunit vaccines because they are relatively inexpensive to grow, genetically tractable, easily scaled to large volumes, have a short generation time, and are devoid of inflammatory, viral, or prion contaminants often present in other systems. We tested whether algal chloroplasts can produce malaria transmission blocking vaccine candidates, Plasmodium falciparum surface protein 25 (Pfs25) and 28 (Pfs28). Antibodies that recognize Pfs25 and Pfs28 disrupt the sexual development of parasites within the mosquito midgut, thus preventing transmission of malaria from one human host to the next. These proteins have been difficult to produce in traditional recombinant systems because they contain tandem repeats of structurally complex epidermal growth factor-like domains, which cannot be produced in bacterial systems, and because they are not glycosylated, so they must be modified for production in eukaryotic systems. Production in algal chloroplasts avoids these issues because chloroplasts can fold complex eukaryotic proteins and do not glycosylate proteins. Here we demonstrate that algae are the first recombinant system to successfully produce an unmodified and aglycosylated version of Pfs25 or Pfs28. These antigens are structurally similar to the native proteins and antibodies raised to these recombinant proteins recognize Pfs25 and Pfs28 from P. falciparum. Furthermore, antibodies to algae-produced Pfs25 bind the surface of in-vitro cultured P. falciparum sexual stage parasites and exhibit transmission blocking activity. Thus

A phase IIb multicentre study comparing the efficacy of trabectedin to doxorubicin in patients with advanced or metastatic untreated soft tissue sarcoma: The TRUSTS trial

NARCIS (Netherlands)

Bui-Nguyen, B.; Butrynski, J.E.; Penel, N.; Blay, J.Y.; Isambert, N.; Milhem, M.; Kerst, J.M.; Reyners, A.K.; Litiere, S.; Marreaud, S.; Collin, F.; Graaf, W.T.A. van der

2015-01-01

PURPOSE: To evaluate whether trabectedin as first-line chemotherapy for advanced/metastatic soft tissue sarcoma prolongs progression-free survival (PFS), compared to doxorubicin and, in the phase IIb part here, to select the most appropriate trabectedin treatment schedule (3-hour or 24-hour

Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel: a subset analysis of EORTC 24971 study

NARCIS (Netherlands)

Psyrri, A.; Fortpied, C.; Koutsodontis, G.; Avgeris, M.; Kroupis, C.; Goutas, N.; Menis, J.; Herman, L.; Giurgea, L.; Remenar, E.; Degardin, M.; Pateras, I.S.; Langendijk, J.A.; Herpen, C.M.L. van; Awada, A.; Germa-Lluch, J.R.; Kienzer, H.R.; Licitra, L.; Vermorken, J.B.

2017-01-01

Background: EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF (docetaxel, cisplatin, 5-fluorouracil) over PF (cisplatin/5-fluorouracil), in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable head and neck squamous cell

Evaluation of the impact of tumor HPV status on outcome in patients with locally advanced unresectable head and neck squamous cell carcinoma (HNSCC) receiving cisplatin, 5-fluorouracil with or without docetaxel : a subset analysis of EORTC 24971 study

NARCIS (Netherlands)

Psyrri, A; Fortpied, C; Koutsodontis, G; Avgeris, M; Kroupis, C; Goutas, N; Menis, J; Herman, L; Giurgea, L; Remenar, E; Degardin, M; Pateras, I S; Langendijk, J A; van Herpen, C; Awada, A; Germà-Lluch, J R; Kienzer, H R; Licitra, L; Vermorken, J B

Background: EORTC 24971 was a phase III trial demonstrating superiority of induction regimen TPF over PF, in terms of progression-free (PFS) and overall survival (OS) in locoregionally advanced unresectable HNSCC. We conducted a retrospective analysis of prospectively collected data aiming to

Influence of HPV-status on survival of patients with tonsillar carcinomas (TSCC) treated by CO2-laser surgery plus risk adapted therapy - A 10 year retrospective single centre study.

Science.gov (United States)

Hoffmann, Markus; Quabius, Elgar Susanne; Tribius, Silke; Gebhardt, Stephan; Görögh, Tibor; Hedderich, Jürgen; Huber, Karen; Dunst, Jürgen; Ambrosch, Petra

2018-01-28

The positive prognostic value of HPV-infections in oropharyngeal squamous cell cancer (OSCC) patients has led to the initiation of prospective clinical trials testing the value of treatment de-escalation. It is unclear how to define patients potentially benefiting from de-escalated treatment, whether a positive smoking history impacts survival data and what kind of de-escalation might be best. Here, we investigate the effect of HPV-status, smoking habit and treatment design on overall survival (OS) and progression free survival (PFS) of 126 patients with tonsillar SCC (TSCC) who underwent CO 2 -laser-surgery and risk adapted adjuvant treatment. HPV-DNA-, HPV-mRNA-, and p16 INK4A -expression were analysed and results were correlated to OS and PFS. Factors tested for prognostic value included HPV-status, p16 INK4A -protein expression, therapy and smoking habit. Log rank test and p-values ≤0.05 defined significant differences between groups. The highest accuracy of data with highest significance in this study is given when the HPV-RNA-status is considered. Using p16 INK4A -expression alone or in combination with HPV-DNA-status, would have misclassified 23 and 7 patients, respectively. Smoking fully abrogates the positive impact of HPV-infection in TSCC on survival. Non-smoking HPV-positive TSCC patients show 10-year OS of 100% and 90.9% PFS when treated with adjuvant RCT. The presented data show that high-precision HPV-detection methods are needed, specifically when treatment decisions are based on the results. Furthermore, smoking habit should be included in all studies and clinical trials testing HPV-associated survival. Adjuvant RCT especially for HPV-positive non-smokers may help to avoid distant failure. Copyright © 2017 Elsevier B.V. All rights reserved.

Glioblastoma Recurrence Patterns After Radiation Therapy With Regard to the Subventricular Zone

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Adeberg, Sebastian, E-mail: Sebastian.adeberg@med.uni-heidelberg [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); König, Laila; Bostel, Tilman; Harrabi, Semi; Welzel, Thomas [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Debus, Jürgen [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Heidelberg Ion Therapy Center, Heidelberg (Germany); DKFZ Clinical Cooperation Unit Radiation Oncology, German Cancer Research Center Heidelberg (Germany); Combs, Stephanie E. [Department of Radiation Oncology, University Hospital of Heidelberg, Heidelberg (Germany); Heidelberg Ion Therapy Center, Heidelberg (Germany)

2014-11-15

Purpose: We evaluated the influence of tumor location and tumor spread in primary glioblastoma (GBM), with respect to the subventricular zone (SVZ), on recurrence behavior, progression-free survival (PFS), and overall survival (OS). Methods and Materials: 607 patients (376 male and 231 female) with a median age of 61.3 years (range, 3.0-87.9 years) and primary GBM treated with radiation therapy (RT) from 2004 to 2012 at a single institution were included in this retrospective study. Preoperative images and follow-up examination results were assessed to evaluate tumor location. Tumors were classified according to the tumor location in relation to the SVZ. Results: The median PFS of the study population was 5.2 months (range, 1-91 months), and the median OS was 13.8 months (range, 1-102 months). Kaplan-Meier analysis showed that tumor location in close proximity to the SVZ was associated with a significant decline in PFS and OS (4.8 and 12.3 months, respectively; each P<.001). Furthermore, in cases where tumors were involved with the SVZ, distant cerebral progression (43.8%; P=.005) and multifocal progression (39.8%; P=.008) were more common. Interestingly, opening of the ventricle during the previous surgery showed no impact on PFS and OS. Conclusion: GBM in close proximity to the SVZ was associated with decreased survival and had a higher risk of multifocal or distant progression. Ventricle opening during surgery had no effect on survival rates.

Red blood cell distribution width as a predictor of survival in nasal-type, extranodal natural killer/T-cell lymphoma.

Science.gov (United States)

Luo, Huaichao; Quan, Xiaoying; Song, Xiao-Yu; Zhang, Li; Yin, Yilin; He, Qiao; Cai, Shaolei; Li, Shi; Zeng, Jian; Zhang, Qing; Gao, Yu; Yu, Sisi

2017-11-03

We retrospectively enrolled 191 nasal-type, extranodal natural killer/T-cell lymphoma (ENKTL) patients newly diagnosed from 2008 to 2016 at the Sichuan Cancer Hospital, in order to evaluate the relationship between disease outcomes, demographic and clinical factors, and red blood cell distribution width (RDW). C-index, fisher's exact test, univariate analysis, and cox regression analysis were applied. The median age of patients was 44 years and 134 (70%) were men. The cutoff of RDW was 46.2 fL determined by Cutoff Finder. Patients with RDW≤46.2 fL had significantly better progression-free survival (PFS) (3-year PFS, 80.4% vs. 63.1%; P =0.01) and overall survival (OS) (3-year OS, 83.2% vs. 65.5%; P =0.004) than those with RDW>46.2 fL. Multivariate analysis demonstrated that elevated RDW is an independent adverse predictor of OS ( P =0.021, HR=2.04). RDW is an independent predictor of survival outcomes in ENKTL, which we found to be superior to both the prognostic index of natural killer lymphoma (PINK) and the Korean Prognostic Index (KPI) in discriminating patients with different outcomes in low-risk and high-risk groups (all P KPI, and PINK showed more powerful prognostic value than corresponding original models. RDW represents an easily available and inexpensive marker for risk stratification in patients with ENKTL treated with radiotherapy-based treatment. Further prospective studies are warranted to confirm the prognostic value of RDW in ENKTL.

Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

International Nuclear Information System (INIS)

Topkan, Erkan; Parlak, Cem; Topuk, Savas; Pehlivan, Berrin

2012-01-01

Glutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE). However, there are concerns that Gln might stimulate tumor growth, and therefore negatively impact the outcomes of anticancer treatment. We retrospectively investigated the effect of co-administration of oral Gln during C-CRT on survival outcomes of patients with stage IIIB non-small cell lung carcinoma (NSCLC). We additionally evaluated role of oral Gln in preventing C-CRT-induced weight change, acute and late toxicities. The study included 104 patients: 56 (53.8%) received prophylactic powdered Gln (Gln+) orally at a dose of 10 g/8 h and 48 (46.2%) did not receive Gln (Gln-) and served as controls. The prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy fractions. Primary endpoints of progression-free survival (PFS), local/regional progression-free survival (LRPFS), and overall survival (OS) were correlated with status of Gln supplementation. Oral Gln was well tolerated except for mild nausea/vomiting in 14 (25.0%) patients. There was no C-CRT-related acute or late grade 4–5 toxicity. Administration of Gln was associated with a decrease in the incidence of grade 3 acute radiation-induced esophagitis (RIE) (7.2% vs. 16.7% for Gln+ vs. Gln-; p=0.02) and late-RIE (0% vs. 6.3%; p=0.06), a reduced need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04), and reduced incidence of weight loss (44.6% vs. 72.9%; p=0.002). At a median follow-up of 24.2 months (range 9.2-34.4) the median OS, LRPFS, and PFS for Gln+ vs. Gln- cohorts were 21.4 vs. 20.4 (p=0.35), 14.2 vs.11.3 (p=0.16), and 10.2 vs. 9.0 months (p=0.11), respectively. In our study, supplementation with Gln during C-CRT had no detectable negative impact on tumor control and survival outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a beneficial effect with respect to prevention of weight loss

Early α-fetoprotein response predicts survival in patients with advanced hepatocellular carcinoma treated with sorafenib

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Lee SH

2015-04-01

Full Text Available Sangheun Lee,1,* Beom Kyung Kim,2–5,* Seung Up Kim,2–5 Jun Yong Park,2–5 Do Young Kim,2–5 Sang Hoon Ahn,2–6 Kwang-Hyub Han2–6 1Department of Internal Medicine, International St Mary’s Hospital, Catholic Kwandong University, Incheon Metropolitan City, Republic of Korea; 2Department of Internal Medicine, 3Institute of Gastroenterology, 4Liver Cancer Special Clinic, Yonsei University College of Medicine, Seoul, Republic of Korea; 5Liver Cirrhosis Clinical Research Center, Seoul, Republic of Korea; 6Brain Korea 21 Project for Medical Science, Seoul, Republic of Korea.   *These authors contributed equally to this work Background: It is not clear whether tumor marker responses can predict survival during sorafenib treatment in hepatocellular carcinoma (HCC. We investigated whether the α-fetoprotein (AFP response is associated with survival in patients with advanced HCC treated with sorafenib. Methods: We retrospectively reviewed the records of 126 patients with advanced HCC treated with sorafenib between 2007 and 2012. An AFP response was defined as >20% decrease from baseline. At 6–8 weeks after commencing sorafenib, AFP and radiological responses were assessed by modified Response Evaluation Criteria in Solid Tumors. Results: The median overall survival (OS and progression-free survival (PFS were 6.2 and 3.5 months, respectively. Of the study population, a partial response (PR was identified in 5 patients (4.0%, stable disease (SD in 65 patients (51.6%, and progressive disease (PD in 57 patients (44.4%, respectively. AFP non-response was an independent prognostic factor for poor OS (median 10.9 months for AFP response vs 5.2 months for AFP non-response, together with Child-Pugh B, tumor diameter ≥10 cm, and portal vein invasion (all P<0.05, and PFS (median 5.3 months for AFP response vs 2.9 months for AFP non-response, together with tumor diameter ≥10 cm and portal vein invasion (all P<0.05. SD or PR was more frequently found

PFS: a distributed and customizable file system

OpenAIRE

Bosch, H.G.P.; Mullender, Sape J.

1996-01-01

In this paper we present our ongoing work on the Pegasus File System (PFS), a distributed and customizable file system that can be used for off-line file system experiments and on-line file system storage. PFS is best described as an object-oriented component library from which either a true file system or a file-system simulator can be constructed. Each of the components in the library is easily replaced by another implementation to accommodate a wide range of applications.

Hemithoracic Intensity Modulated Radiation Therapy After Pleurectomy/Decortication for Malignant Pleural Mesothelioma: Toxicity, Patterns of Failure, and a Matched Survival Analysis

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Chance, William W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rice, David C. [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tsao, Anne S. [Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Fontanilla, Hiral P. [Princeton Radiation Oncology, Monroe Township, New Jersey (United States); Liao, Zhongxing; Chang, Joe Y.; Tang, Chad; Pan, Hubert Y.; Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mehran, Reza J. [Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gomez, Daniel R., E-mail: dgomez@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2015-01-01

Purpose: To investigate safety, efficacy, and recurrence after hemithoracic intensity modulated radiation therapy after pleurectomy/decortication (PD-IMRT) and after extrapleural pneumonectomy (EPP-IMRT). Methods and Materials: In 2009-2013, 24 patients with mesothelioma underwent PD-IMRT to the involved hemithorax to a dose of 45 Gy, with an optional integrated boost; 22 also received chemotherapy. Toxicity was scored with the Common Terminology Criteria for Adverse Events v4.0. Pulmonary function was compared at baseline, after surgery, and after IMRT. Kaplan-Meier analysis was used to calculate overall survival (OS), progression-free survival (PFS), time to locoregional failure, and time to distant metastasis. Failures were in-field, marginal, or out of field. Outcomes were compared with those of 24 patients, matched for age, nodal status, performance status, and chemotherapy, who had received EPP-IMRT. Results: Median follow-up time was 12.2 months. Grade 3 toxicity rates were 8% skin and 8% pulmonary. Pulmonary function declined from baseline to after surgery (by 21% for forced vital capacity, 16% for forced expiratory volume in 1 second, and 19% for lung diffusion of carbon monoxide [P for all = .01]) and declined still further after IMRT (by 31% for forced vital capacity [P=.02], 25% for forced expiratory volume in 1 second [P=.01], and 30% for lung diffusion of carbon monoxide [P=.01]). The OS and PFS rates were 76% and 67%, respectively, at 1 year and 56% and 34% at 2 years. Median OS (28.4 vs 14.2 months, P=.04) and median PFS (16.4 vs 8.2 months, P=.01) favored PD-IMRT versus EPP-IMRT. No differences were found in grade 4-5 toxicity (0 of 24 vs 3 of 24, P=.23), median time to locoregional failure (18.7 months vs not reached, P not calculable), or median time to distant metastasis (18.8 vs 11.8 months, P=.12). Conclusions: Hemithoracic intensity modulated radiation therapy after pleurectomy/decortication produced little high-grade toxicity but

Activation of phosphoinositide 3-kinase/Akt/mechanistic target of rapamycin pathway and response to everolimus in endocrine receptor-positive metastatic breast cancer – A retrospective pilot analysis and viewpoint

Directory of Open Access Journals (Sweden)

Jyoti Bajpai

2017-01-01

Full Text Available Introduction: Biomarkers predictive of response to mechanistic target of rapamycin (mTOR inhibitor, everolimus, in endocrine receptor (ER-positive metastatic breast cancer (MBC are a work in progress. We evaluated the feasibility of directly measuring mTOR activity and phosphatase and tensin homolog (PTEN expression and correlating their expression with response and survival. Materials and Methods: MBC patients who received everolimus with endocrine therapy (ET after progression on an aromatase inhibitor and had adequate tissue preservation for estimation of mTOR activity and PTEN expression were selected for analysis from a prospectively maintained database. Progression-free survival (PFS and overall survival (OS were estimated by Kaplan–Meier method, and correlation between mTOR activity and PTEN expression with survival was done by log-rank test. Results: Thirteen ER-positive MBC patients were available for analysis. PTEN expression was lost in 11/13 (84.6% patients and retained in 2/13 patients (15.4%. mTOR activity was absent in four patients (30.7%, weak in six patients (46.1%, and moderate in 3 patients (23.2%. Median PFS for the entire population was 2.5 months while median OS was not reached. Patients with an absent mTOR activity showed a longer PFS (5 vs. 1.5 vs. 2 months than those with weak and moderate activity, respectively (P = 0.043. There was no correlation between loss of PTEN expression and PFS. Conclusions: Measurement of direct mTOR activity in patients with MBC receiving everolimus/ET combination appears feasible. Absent mTOR activity may predict for longer PFS with everolimus-ET combination and requires further study.

Meta-analysis of single-arm survival studies: a distribution-free approach for estimating summary survival curves with random effects.

Science.gov (United States)

Combescure, Christophe; Foucher, Yohann; Jackson, Daniel

2014-07-10

In epidemiologic studies and clinical trials with time-dependent outcome (for instance death or disease progression), survival curves are used to describe the risk of the event over time. In meta-analyses of studies reporting a survival curve, the most informative finding is a summary survival curve. In this paper, we propose a method to obtain a distribution-free summary survival curve by expanding the product-limit estimator of survival for aggregated survival data. The extension of DerSimonian and Laird's methodology for multiple outcomes is applied to account for the between-study heterogeneity. Statistics I(2)  and H(2) are used to quantify the impact of the heterogeneity in the published survival curves. A statistical test for between-strata comparison is proposed, with the aim to explore study-level factors potentially associated with survival. The performance of the proposed approach is evaluated in a simulation study. Our approach is also applied to synthesize the survival of untreated patients with hepatocellular carcinoma from aggregate data of 27 studies and synthesize the graft survival of kidney transplant recipients from individual data from six hospitals. Copyright © 2014 John Wiley & Sons, Ltd.

Reduced estimated glomerular filtration rate (eGFR 73 m2 ) at first transurethral resection of bladder tumour is a significant predictor of subsequent recurrence and progression.

Science.gov (United States)

Blute, Michael L; Kucherov, Victor; Rushmer, Timothy J; Damodaran, Shivashankar; Shi, Fangfang; Abel, E Jason; Jarrard, David F; Richards, Kyle A; Messing, Edward M; Downs, Tracy M

2017-09-01

To evaluate if moderate chronic kidney disease [CKD; estimated glomerular filtration rate (eGFR) 73 m 2 ] is associated with high rates of non-muscle-invasive bladder cancer (NMIBC) recurrence or progression. A multi-institutional database identified patients with serum creatinine values prior to first transurethral resection of bladder tumour (TURBT). The CKD-epidemiology collaboration formula calculated patient eGFR. Cox proportional hazards models evaluated associations with recurrence-free (RFS) and progression-free survival (PFS). In all, 727 patients were identified with a median (interquartile range [IQR]) patient age of 69.8 (60.1-77.6) years. Data for eGFR were available for 632 patients. During a median (IQR) follow-up of 3.7 (1.5-6.5) years, 400 (55%) patients had recurrence and 145 (19.9%) patients had progression of tumour stage or grade. Moderate or severe CKD was identified in 183 patients according to eGFR. Multivariable analysis identified an eGFR of 73 m 2 (hazard ratio [HR] 1.5, 95% confidence interval [CI]: 1.2-1.9; P = 0.002) as a predictor of tumour recurrence. The 5-year RFS rate was 46% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 27% for patients with an eGFR of 73 m 2 (P 73 m 2 (HR 3.7, 95% CI: 1.75-7.94; P = 0.001) was associated with progression to muscle-invasive disease. The 5-year PFS rate was 83% for patients with an eGFR of ≥60 mL/min/1.73 m 2 and 71% for patients with an eGFR of 73 m 2 (P = 0.01). Moderate CKD at first TURBT is associated with reduced RFS and PFS. Patients with reduced renal function should be considered for increased surveillance. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Primary Tumour Resection Could Improve the Survival of Unresectable Metastatic Colorectal Cancer Patients Receiving Bevacizumab-Containing Chemotherapy

Directory of Open Access Journals (Sweden)

Zhiming Wang

2016-09-01

Full Text Available Background: The effect of primary tumour resection (PTR among metastatic colorectal cancer (mCRC patients remains controversial. Combination chemotherapy with bevacizumab could improve the clinical outcomes of these patients, which might change the importance of PTR in the multi-disciplinary treatment pattern. Methods: We performed a non-randomized prospective controlled study of mCRC pts whose performance status (PS scored ≤2 and who received bevacizumab combination chemotherapy (FOLFOX/XELOX/FOLFIRI as a first-line therapy. These patients were classified into the PTR group and the IPT (intact primary tumour group according to whether they underwent PTR before receiving the systemic therapy. The progression free survival (PFS time and overall survival (OS time, which were recorded from the start of the primary diagnosis until disease progression and death or last follow-up, were analysed. We also compared severe clinical events (such as emergency surgery, radiation therapy, and stent plantation between the two groups. Results: One hundred and nighty-one mCRC pts (108 male patients and 93 female patients were entered in this prospective observational study. The median age was 57.5 years old. The clinical characteristics (age, gender, performance status, primary tumour site, RAS status, and the number of metastatic organs did not significantly differ between the two groups. The median PFS and OS times of the PTR group were superior than those of the IPT group (10.0 vs 7.8 months, p Conclusions: The mCRC patients who received PTR and bevacizumab combination chemotherapy had better clinical outcomes than patients who did not receive PTR. PTR also decreased the incidence of severe clinical events and improved quality of life.

Experimental peptide receptor radionuclide therapy in radioiodine negative somatostatin receptor positive thyroid cancer

International Nuclear Information System (INIS)

Nilica, B.; Kroiss, A.; Putzer, D.; Uprimmy, C.; Warwitz, B.; Kendler, D.; Waitz, D.; Virgolini, I.

2015-01-01

Full text of publication follows. Purpose: This retrospective analysis evaluated the time to progression (TTP), progression free survival (PFS) and overall survival (OS) in patients with radioiodine negative thyroid cancer who had undergone peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTA-TATE, 177 Lu-DOTA-LAN, 90 Y-DOTA-TOC or 90 Y-DOTA-LAN after tumor progression. Methods: Data derived from twenty patients with either differentiated (n=15), anaplastic (n=1) or medullary (n=4) somatostatin receptor positive thyroid cancer who had received treatment with PRRT after tumor progression. TTP, PFS and OS were defined according to the clinical trial endpoints suggested by the FDA (Food and Drug Administration). Progressive disease was defined by sonography, FDG-PET, Ga-DOTA-TOC-PET, or CT (RECIST Criteria). Results: In 17 patients the median overall survival time after the first PRRT was 17.3 (range: 0.1 - 109.7) months. Three patients still alive are actually showing stable disease. The median of PFS in 20 Patients (6 with more than one PRRT-cycle or PRRT-substance) has been 10.9 (range: 0.1 - 44.0) months. The median TTP was 15.6 (range 4.4 to 29.2) months. Conclusion: PRRT appears to be useful in patients with somatostatin receptor positive but radioiodine negative thyroid cancer as a complementary palliative cytotoxic therapy. (authors)

Human mass balance study and metabolite profiling of 14C-niraparib, a novel poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor, in patients with advanced cancer

NARCIS (Netherlands)

van Andel, Lotte; Zhang, Z; Lu, S.; Kansra, V; Agarwal, S.; Hughes, L.; Tibben, M.; Gebretensae, A.; Lucas, L.; Hillebrand, Michel J X; Rosing, H.; Schellens, J H M|info:eu-repo/dai/nl/073926272; Beijnen, J H|info:eu-repo/dai/nl/071919570

2017-01-01

Niraparib is an investigational oral, once daily, selective poly(ADP-Ribose) polymerase (PARP)-1 and PARP-2 inhibitor. In the pivotal Phase 3 NOVA/ENGOT/OV16 study, niraparib met its primary endpoint of improving progression-free survival (PFS) for adult patients with recurrent, platinum sensitive,

Clinical outcomes and survival surrogacy studies of prostate-specific antigen declines following enzalutamide in men with metastatic castration-resistant prostate cancer previously treated with docetaxel.

Science.gov (United States)

Armstrong, Andrew J; Saad, Fred; Phung, De; Dmuchowski, Carl; Shore, Neal D; Fizazi, Karim; Hirmand, Mohammad; Forer, David; Scher, Howard I; Bono, Johann De

2017-06-15

In the AFFIRM trial, enzalutamide significantly increased overall survival (OS) for men with metastatic castration-resistant prostate cancer (mCRPC) after chemotherapy versus placebo and significantly decreased prostate-specific antigen (PSA) levels. The goal of this post hoc analysis was to associate levels of PSA decline from baseline after enzalutamide with clinical outcomes in the postchemotherapy mCRPC setting. Men in the AFFIRM trial (n = 1199) were grouped by maximal PSA decline in the first 90 days of treatment. Kaplan-Meier estimates evaluated the association of defined PSA changes from baseline with OS, progression-free survival (PFS), radiographic PFS (rPFS), and pain response. Each PSA decline category was assessed for OS surrogacy using Prentice criteria, proportion of treatment effect explained (PTE), and proportion of variation explained. Men treated with enzalutamide had improved OS (hazard ratio, 0.63; P 19.0; P .20). PSA declines of any, ≥30%, and ≥50% following enzalutamide were associated with greater clinical and pain response and improvements in PFS and OS. Surrogacy of PSA decline for OS was not fully established, possibly due to lack of PSA declines with placebo, and discordant results between PSA and imaging responses over time, and because some declines were not durable due to rapid resistance development. However, a lack of PSA decline by 90 days following enzalutamide treatment was a poor prognosis indicator in this setting. Conclusions from sensitivity analyses of maximal PSA decline from baseline over the entire treatment period are consistent with PSA declines restricted to the first 90 days. Cancer 2017;123:2303-2311. © 2017 American Cancer Society. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Low Serum Vitamin D Levels Are Associated With Inferior Survival in Follicular Lymphoma: A Prospective Evaluation in SWOG and LYSA Studies.

Science.gov (United States)

Kelly, Jennifer L; Salles, Gilles; Goldman, Bryan; Fisher, Richard I; Brice, Pauline; Press, Oliver; Casasnovas, Olivier; Maloney, David G; Soubeyran, Pierre; Rimsza, Lisa; Haioun, Corinne; Xerri, Luc; LeBlanc, Michael; Tilly, Hervé; Friedberg, Jonathan W

2015-05-01

Recent literature reports a potential association between high vitamin D and improved lymphoma prognosis. We evaluated the impact of pretreatment vitamin D on follicular lymphoma (FL) outcome. SWOG participants were previously untreated patients with FL enrolled onto SWOG clinical trials (S9800, S9911, or S0016) involving CHOP chemotherapy plus an anti-CD20 antibody (rituximab or iodine-131 tositumomab) between 1998 and 2008. Participants included in our second independent cohort were also previously untreated patients with FL enrolled onto the Lymphoma Study Association (LYSA) PRIMA trial of rituximab plus chemotherapy (randomly assigned to rituximab maintenance v observation) between 2004 and 2007. Using the gold-standard liquid chromatography-tandem mass spectrometry method, 25-hydroxyvitamin D was measured in stored baseline serum samples. The primary end point was progression-free survival (PFS). After a median follow-up of 5.4 years, the adjusted PFS and overall survival hazard ratios for the SWOG cohort were 1.97 (95% CI, 1.10 to 3.53) and 4.16 (95% CI, 1.66 to 10.44), respectively, for those who were vitamin D deficient (< 20 ng/mL; 15% of cohort). After a median follow-up of 6.6 years, the adjusted PFS and overall survival hazard ratios for the LYSA cohort were 1.50 (95% CI, 0.93 to 2.42) and 1.92 (95% CI, 0.72 to 5.13), respectively, for those who were vitamin D deficient (< 10 ng/mL; 25% of cohort). Although statistical significance was not reached in the LYSA cohort, the consistent estimates of association between low vitamin D levels and FL outcomes in two independent cohorts suggests that serum vitamin D might be the first potentially modifiable factor to be associated with FL survival. Further investigation is needed to determine the effects of vitamin D supplementation in this clinical setting. © 2015 by American Society of Clinical Oncology.

Treatment Outcome of Mucosa Associated Lymphoid Tissue (MALT) Marginal Zone Non-Hodgkin's Lymphoma. Single Institutional Experience

International Nuclear Information System (INIS)

Hamada, E.; Omar, H.; Abd El-Kader, Y.; Makram, O.

2003-01-01

To evaluate the treatment outcome in patients with mucosa associated lymphoid tissue (MALT) lymphoma in terms of response to treatment, progression-free and overall survivals as well as prognostic factors. Patients and Methods: Between 1995 and 2002,40 patients with clinical stages (CS) I-IV MALT lymphoma were treated at NEMROCK. The progression free survival (PFS) and overall survival (OAS) were calculated using the Kaplan Meier technique. Thirty-one patients (77.5%) had CS I-II and 9 (22.5%) had CS III-IV disease. Twenty of the 31 CS I-II patients received radiation therapy alone, five patients received chemotherapy, while three patients were treated by triple therapy (Amoxicillin, Omeperazole, Clarithromycin). Among the 9 CS III-IV patients, treatment included chemotherapy alone (6 patients), chemo radiation (2 patients) and surgery (one patient). The median followup period was 40 months. 19 out of twenty patients with CS I-II treated by radiation therapy alone had a 95% response rate (CR 85% - PR 10%). Among the study population (40 patients), the 5 year OAS and PFS were 86% and 66%, respectively. The 5 year OAS was 86% and PFS was 72% among CS III patients; the corresponding estimates in CS III-IV patients were 70% and 28%, respectively. Using multivariate analysis, there was a significant correlation between the stage of the disease, site of presentation (non GIT) and the overall survival. Modest doses of radiation therapy provide better local control in patients with early stage MALT lymphoma. The poor PFS in advanced staged disease suggests the need for further clinical trials evaluating novel drug approaches taking into consideration the biological behavior and the indolent nature of such disease entity

Correlation of degree of hypothyroidism with survival outcomes in patients with metastatic renal cell carcinoma receiving vascular endothelial growth factor receptor tyrosine kinase inhibitors.

Science.gov (United States)

Bailey, Erin B; Tantravahi, Srinivas K; Poole, Austin; Agarwal, Archana M; Straubhar, Alli M; Batten, Julia A; Patel, Shiven B; Wells, Chesley E; Stenehjem, David D; Agarwal, Neeraj

2015-06-01

Hypothyroidism is a common adverse effect of vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR-TKI) therapy in patients with metastatic renal cell carcinoma (mRCC). Some studies have shown an association with improved survival. However, hypothyroidism severity has not been correlated with survival outcomes. We report the incidence and severity of VEGFR-TKI therapy-associated hypothyroidism in correlation with the survival outcomes of patients with mRCC. A retrospective analysis of patients with mRCC who received VEGFR-TKIs (2004 through 2013) was conducted from a single institutional database. Hypothyroidism, progression-free survival (PFS), and overall survival (OS) were assessed. Univariate and multivariate analyses were performed using the Kaplan-Meier method and Cox proportional hazard models. Of 125 patients with mRCC, 65 were eligible. Their median age was 59 years (range, 45-79 years), and 46 (70.8%) were male. Hypothyroidism occurred in 25 patients (38.5%), of whom 13 had a peak thyroid-stimulating hormone (TSH) level > 10 mIU/L during treatment. The median OS was significantly longer in patients with a peak TSH > 10 mIU/L than in patients with a peak TSH of ≤ 10 mIU/L (not reached vs. 21.4 months, P = .005). On multivariate analysis, risk criteria, number of previous therapies, and severe hypothyroidism (TSH > 10 mIU/L) during VEGFR-TKI therapy remained significant for improvements in PFS and OS. The severity of VEGFR-TKI therapy-associated hypothyroidism (TSH > 10 mIU/L) was associated with improved survival outcomes in patients with mRCC and should not necessitate a dose reduction or therapy discontinuation. Copyright © 2015 Elsevier Inc. All rights reserved.

The efficacy and safety of standardized allergen-removed Rhus verniciflua extract as maintenance therapy after first-line chemotherapy in patients with advanced non-small cell lung cancer.

Science.gov (United States)

Lee, Jinsoo; Chae, Jean; Lee, Sookyung; Kim, Kyungsuk; Eo, Wankyu; Kim, Sehyun; Choi, Woncheol; Cheon, Seong Ha

2013-01-01

Chemotherapy improves the survival of patients with advanced non-small cell lung cancer (NSCLC), but tumor progression is often inevitable. Strategies are needed to improve the therapeutic efficacy of chemotherapy. Over recent years, there has been increasing interest in the role of maintenance therapy after first-line chemotherapy. We investigated the efficacy and safety of standardized allergen-removed Rhus verniciflua Stokes extract (aRVS) as maintenance therapy in patients with non-progressive disease following first-line chemotherapy. We reviewed the medical records of 33 patients with advanced NSCLC, who started treatment with aRVS in a state of tumor regression or stable disease after completion of four or six cycles of induction chemotherapy at the Integrative Cancer Center, Kyung Hee University Hospital at Gangdong from June 2006 to April 2012. The primary objective of this study was progression-free survival (PFS) of aRVS as maintenance therapy. Secondary objectives included assessments of disease control rate (DCR), overall survival (OS), and the safety of aRVS treatment. The median PFS was 5.2 months with a 6- and 12-month PFS rate of 40.6% and 12.9%, respectively. The DCR was 93.9% and the median OS was 34.8 months. The overall survival rates at 12, 24, and 36 months were 84.2%, 76.7% and 49.9%, respectively. We observed no hematologic toxicity, nephrotoxicity, or hepatotoxicity during aRVS treatment. In conclusion, maintenance therapy with aRVS for patients with advanced NSCLC is well-tolerated and offers encouraging improved PFS and OS compared with historical controls. Our data provide further evidence that aRVS may be used beyond disease progression in this clinical setting.

The flare in alkaline phosphatase activity post-orchidectomy predicts which patient may benefit from early chemotherapy in metastatic prostate cancer

NARCIS (Netherlands)

Pelger, Rob C. M.; Lycklama A Nijeholt, Guus A. B.; Zwinderman, Aielko H.; Hamdy, Neveen A. T.

2002-01-01

BACKGROUND: A flare in serum alkaline phosphatase (ALP) activity post-orchidectomy has been shown to be of negative prognostic value for progression-free survival (PFS) in patients with prostate cancer. The aim of this study was to investigate whether a flare in ALP may help identify patients in

Dose-Escalated Hypofractionated Intensity-Modulated Radiotherapy in High-Risk Carcinoma of the Prostate: Outcome and Late Toxicity

Directory of Open Access Journals (Sweden)

David Thomson

2012-01-01

Results. Median followup was 84 months. Five-year overall survival (OS was 83% and biochemical progression-free survival (bPFS was 50% for 57 Gy. Five-year OS was 75% and bPFS 58% for 60 Gy. At 7 years, toxicity by RTOG criteria was acceptable with no grade 3 or above toxicity. Compared with baseline, there was no significant change in urinary symptoms at 2 or 7 years. Bowel symptoms were stable between 2 and 7 years. All patients continued to have significant sexual dysfunction. Conclusion. In high-risk prostate cancer, dose-escalated hypofractionated radiotherapy using IMRT results in encouraging outcomes and acceptable late toxicity.

Antibody responses to two new Lactococcus lactis-produced recombinant Pfs48/45 and Pfs230 proteins increase with age in malaria patients living in the Central Region of Ghana.

Science.gov (United States)

Acquah, Festus K; Obboh, Evans K; Asare, Kwame; Boampong, Johnson N; Nuvor, Samuel Victor; Singh, Susheel K; Theisen, Michael; Williamson, Kim C; Amoah, Linda Eva

2017-08-01

Recent advances in malaria control efforts have led to an increased number of national malaria control programmes implementing pre-elimination measures and demonstrated the need to develop new tools to track and control malaria transmission. Key to understanding transmission is monitoring the prevalence and immune response against the sexual stages of the parasite, known as gametocytes, which are responsible for transmission. Sexual-stage specific antigens, Pfs230 and Pfs48/45, have been identified and shown to be targets for transmission blocking antibodies, but they have been difficult to produce recombinantly in the absence of a fusion partner. Regions of Pfs48/45 and Pfs230 known to contain transmission blocking epitopes, 6C and C0, respectively, were produced in a Lactococcus lactis expression system and used in enzyme linked immunosorbent assays to determine the seroreactivity of 95 malaria patients living in the Central Region of Ghana. Pfs48/45.6C and Pfs230.C0 were successfully produced in L. lactis in the absence of a fusion partner using a simplified purification scheme. Seroprevalence for L. lactis-produced Pfs48/45.6C and Pfs230.C0 in the study population was 74.7 and 72.8%, respectively. A significant age-dependent increase in antibody titers was observed, which suggests a vaccine targeting these antigens could be boosted during a natural infection in the field.

Altered expression of HER-2 and the mismatch repair genes MLH1 and MSH2 predicts the outcome of T1 high-grade bladder cancer.

Science.gov (United States)

Sanguedolce, Francesca; Cormio, Antonella; Massenio, Paolo; Pedicillo, Maria C; Cagiano, Simona; Fortunato, Francesca; Calò, Beppe; Di Fino, Giuseppe; Carrieri, Giuseppe; Bufo, Pantaleo; Cormio, Luigi

2018-04-01

The identification of factors predicting the outcome of stage T1 high-grade bladder cancer (BC) is a major clinical issue. We performed immunohistochemistry to assess the role of human epidermal growth factor receptor-2 (HER-2) and microsatellite instability (MSI) factors MutL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in predicting recurrence and progression of T1 high-grade BCs having undergone transurethral resection of bladder tumor (TURBT) alone or TURBT + intravesical instillations of bacillus Calmette-Guerin (BCG). HER-2 overexpression was a significant predictor of disease-free survival (DFS) in the overall as well as in the two patients' population; as for progression-free survival (PFS), it was significant in the overall but not in the two patients' population. MLH1 was an independent predictor of PFS only in patients treated with BCG and MSH2 failed to predict DFS and PFS in all populations. Most importantly, the higher the number of altered markers the lowers the DFS and PFS. In multivariate Cox proportional-hazards regression analysis, the number of altered molecular markers and BCG treatment were significant predictors (p = 0.0004 and 0.0283, respectively) of DFS, whereas the number of altered molecular markers was the only significant predictor (p = 0.0054) of PFS. Altered expression of the proto-oncogene HER-2 and the two molecular markers of genetic instability MLH1 and MSH2 predicted T1 high-grade BC outcome with the higher the number of altered markers the lower the DFS and PFS. These findings provide grounds for further testing them in predicting the outcome of this challenging disease.

Combined CT-guided radiofrequency ablation with systemic chemotherapy improves the survival for nasopharyngeal carcinoma with oligometastasis in liver: Propensity score matching analysis.

Science.gov (United States)

Li, Wang; Bai, Yutong; Wu, Ming; Shen, Lujun; Shi, Feng; Sun, Xuqi; Lin, Caijin; Chang, Boyang; Pan, Changchuan; Li, Zhiwen; Wu, Peihong

2017-08-08

The aim of this study was to retrospectively compare the treatment efficacy of systemic chemotherapy combined with sequential CT-guided radiofrequency ablation (Chemo-RFA) to chemotherapy alone (Chemo-only) in the management of nasopharyngeal carcinoma (NPC) with liver metastasis. Between 2003 and 2011, 328 NPC patients diagnosed with liver metastasis at Sun Yat-sen University Cancer Center were enrolled. One-to-one matched pairs between Chemo-RFA group with the Chemo-only group were generated using propensity score matching. The associations of treatment modality with overall survival (OS) and progression-free survival (PFS) were determined by Cox regression. Of the patients enrolled, 37 patients (11.8 %) received combined treatment, 291 (82.2) received chemotherapy alone. The patients in Chemo-RFA group were more frequently classified as lower number (≤3) of liver metastatic lesions (Poligometastasis in liver, and should be considered if the ablation is technically feasible.

Adding Erlotinib to Chemoradiation Improves Overall Survival but Not Progression-Free Survival in Stage III Non-Small Cell Lung Cancer

Energy Technology Data Exchange (ETDEWEB)

Komaki, Ritsuko, E-mail: rkomaki@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Wei, Xiong [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Blumenschein, George R. [Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Tang, Ximing [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Lee, J. Jack [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Welsh, James W. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Wistuba, Ignacio I. [Department of Translational Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Liu, Diane D. [Department of Biostatatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hong, Waun Ki [Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2015-06-01

Purpose: To test, in a single-arm, prospective, phase 2 trial, whether adding the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to concurrent chemoradiotherapy for previously untreated, locally advanced, inoperable non-small cell lung cancer would improve survival and disease control without increasing toxicity. Methods and Materials: Forty-eight patients with previously untreated non-small cell lung cancer received intensity modulated radiation therapy (63 Gy/35 fractions) on Monday through Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin area under the curve [AUC] = 2) on Mondays, for 7 weeks. All patients also received the EGFR tyrosine kinase inhibitor erlotinib (150 mg orally 1/d) on Tuesday-Sunday for 7 weeks, followed by consolidation paclitaxel–carboplatin. The primary endpoint was time to progression; secondary endpoints were overall survival (OS), toxicity, response, and disease control and whether any endpoint differed by EGFR mutation status. Results: Of 46 patients evaluable for response, 40 were former or never-smokers, and 41 were evaluable for EGFR mutations (37 wild-type [WT] and 4 mutated [all adenocarcinoma]). Median time to progression was 14.0 months and did not differ by EGFR status. Toxicity was acceptable (no grade 5, 1 grade 4, 11 grade 3). Twelve patients (26%) had complete responses (10 WT, 2 mutated), 27 (59%) partial (21 WT, 2 mutated, 4 unknown), and 7 (15%) none (6 WT, 2 mutated, 1 unknown) (P=.610). At 37.0 months' follow-up (range, 3.6-76.5 months) for all patients, median OS time was 36.5 months, and 1-, 2-, and 5-year OS rates were 82.6%, 67.4%, and 35.9%, respectively; none differed by mutation status. Twelve patients had no progression, and 34 had local and/or distant failure. Eleven of 27 distant failures were in the brain (7 WT, 3 mutated, 1 unknown). Conclusions: Toxicity and OS were promising, but time to progression did not meet expectations. The prevalence of

Real-world effectiveness of everolimus-based therapy versus fulvestrant monotherapy in HR(+)/HER2(-) metastatic breast cancer.

Science.gov (United States)

Hao, Yanni; Lin, Peggy L; Xie, Jipan; Li, Nanxin; Koo, Valerie; Ohashi, Erika; Wu, Eric Q; Rogerio, Jaqueline

2015-08-01

Assessing real-world effectiveness of everolimus-based therapy (EVE) versus fulvestrant monotherapy (FUL) among postmenopausal women with hormone receptor-positive (HR(+))/HER2(-) metastatic breast cancer (mBC) after progression on nonsteroidal aromatase inhibitor (NSAI). Medical charts of community-based patients who received EVE or FUL for mBC after NSAI were examined. Progression-free survival (PFS), time on treatment and time to chemotherapy were compared using Kaplan-Meier curves and Cox proportional hazards models adjusting for line of therapy and patient characteristics. 192 patients received EVE and 156 FUL. After adjusting for patient characteristics, EVE was associated with significantly longer PFS than FUL (hazard ratio: 0.71; p = 0.045). EVE was associated with better PFS than FUL among NSAI-refractory postmenopausal HR(+)/HER2(-) mBC patients.

Effectiveness of Cetuximab in Combination with Concurrent Chemoradiotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma: A 1:2 Propensity Score-matched Analysis.

Science.gov (United States)

Wu, Li-Rong; Zhu, Huan-Feng; Xu, Jianhua; Jiang, Xue-Song; Yin, Li; Jiang, Ning; Zong, Dan; Wang, Fei-Jiang; Huang, Sheng-Fu; Bian, Xiu-Hua; Wu, Jian-Feng; Song, Dan; Guo, Wen-Jie; Liu, Ju-Ying; He, Xia

2018-01-01

Background : This study aimed to compare concurrent chemoradiotherapy (CCRT) plus cetuximab (C) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma(NPC). Methods : A total of 682 locoregionally advanced NPC patients who had undergone chemoradiotherapy with or without cetuximab were included. Propensity score-matching method was used to match patients. Progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between the two treatment arms. Results : After matching, 225 patients were identified for the analysis. Compared to CCRT, CCRT plus C was associated with significantly improved 3-year PFS (83.7% vs 71.9%, P = 0.036), LRFS (98.6% vs 90.2%, P = 0.034) but not OS (91.4% vs 85.4%, P = 0.117). Among patients with T4 and/or N3 category, CCRT plus C significantly prolonged 3-year PFS (81.0% vs 61.4%, P = 0.022) and increased 3-year OS (88.0% vs 77.9%, P = 0.086). No significant differences were observed between CCRT plus C and CCRT alone groups with regard to 3-year PFS, OS, LRFS and DMFS rates in stage III patients. Acute oral and oropharyngeal mucositis during radiotherapy were more common in the CCRT plus C than that in CCRT, but late toxicities were comparable. Conclusions: This study reveals that patients with locoregionally advanced NPC could benefit from the addition of cetuximab to CCRT, and this therapeutic gain mainly originated from T4 and/or N3 subgroup although suffering more acute moderate to severe toxicities.

A randomized, double-blind, placebo-controlled phase 2 study of maintenance therapy with tasquinimod in patients with metastatic castration-resistant prostate cancer responsive to or stabilized during first-line docetaxel chemotherapy

DEFF Research Database (Denmark)

Fizazi, K; Ulys, A; Sengeløv, L

2017-01-01

) to receive tasquinimod (0.25-1.0 mg/day orally) or placebo. The primary end point was radiologic progression-free survival (rPFS); secondary efficacy end points included: overall survival (OS); PFS on next-line therapy (PFS 2) and symptomatic PFS, assessed using the Brief Pain Inventory (BPI) questionnaire...... duration of treatment was 18.7 weeks (range 0.6-102.7 weeks) for the tasquinimod arm and 19.2 weeks (range 0.4-80.0 weeks) for the placebo arm. Median (90% CI) rPFS was 31.7 (24.3-53.7) and 22.7 (16.1-25.9) weeks in the tasquinimod and placebo arms, respectively [HR (90% CI) 0.6 (0.4-0.9), P = 0...... in the tasquinimod and placebo arms (97.2% versus 94.3%, respectively), whereas severe TEAEs (NCI-CTC Grade 3-5) incidence was higher in the tasquinimod group (50.7% versus 27.1%). Conclusions: Randomized trials testing new drugs as maintenance can be successfully conducted after chemotherapy in castrate...

Volumetric and MGMT parameters in glioblastoma patients: Survival analysis

International Nuclear Information System (INIS)

Iliadis, Georgios; Kotoula, Vassiliki; Chatzisotiriou, Athanasios; Televantou, Despina; Eleftheraki, Anastasia G; Lambaki, Sofia; Misailidou, Despina; Selviaridis, Panagiotis; Fountzilas, George

2012-01-01

In this study several tumor-related volumes were assessed by means of a computer-based application and a survival analysis was conducted to evaluate the prognostic significance of pre- and postoperative volumetric data in patients harboring glioblastomas. In addition, MGMT (O 6 -methylguanine methyltransferase) related parameters were compared with those of volumetry in order to observe possible relevance of this molecule in tumor development. We prospectively analyzed 65 patients suffering from glioblastoma (GBM) who underwent radiotherapy with concomitant adjuvant temozolomide. For the purpose of volumetry T1 and T2-weighted magnetic resonance (MR) sequences were used, acquired both pre- and postoperatively (pre-radiochemotherapy). The volumes measured on preoperative MR images were necrosis, enhancing tumor and edema (including the tumor) and on postoperative ones, net-enhancing tumor. Age, sex, performance status (PS) and type of operation were also included in the multivariate analysis. MGMT was assessed for promoter methylation with Multiplex Ligation-dependent Probe Amplification (MLPA), for RNA expression with real time PCR, and for protein expression with immunohistochemistry in a total of 44 cases with available histologic material. In the multivariate analysis a negative impact was shown for pre-radiochemotherapy net-enhancing tumor on the overall survival (OS) (p = 0.023) and for preoperative necrosis on progression-free survival (PFS) (p = 0.030). Furthermore, the multivariate analysis confirmed the importance of PS in PFS and OS of patients. MGMT promoter methylation was observed in 13/23 (43.5%) evaluable tumors; complete methylation was observed in 3/13 methylated tumors only. High rate of MGMT protein positivity (> 20% positive neoplastic nuclei) was inversely associated with pre-operative tumor necrosis (p = 0.021). Our findings implicate that volumetric parameters may have a significant role in the prognosis of GBM patients. Furthermore

Inflammatory markers in blood and serum tumor markers predict survival in patients with epithelial appendiceal neoplasms undergoing surgical cytoreduction and intraperitoneal chemotherapy.

Science.gov (United States)

Chua, Terence C; Chong, Chanel H; Liauw, Winston; Zhao, Jing; Morris, David L

2012-08-01

The study examines the role inflammatory and tumor markers as biomarkers to preoperatively predict outcome in patients with epithelial appendiceal neoplasm undergoing cytoreduction and intraperitoneal chemotherapy. Associations between baseline variables, tumor markers [CEA (carcinoembyronic antigen], CA125, CA199), inflammatory markers including neutrophils-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-reactive protein (CRP) with progression-free survival (PFS) and overall survival (OS) were examined in patients undergoing surgical cytoreduction and intraperitoneal chemotherapy for epithelial appendiceal neoplasm. A total of 174 patients with epithelial appendiceal neoplasm (low-grade pseudomyxoma, n = 117; appendiceal cancer, n = 57) underwent cytoreduction. On univariate analysis, all 3 inflammatory and tumor markers predicted for both PFS and OS, respectively; NLR ≤ 2.6 (P = 0.01, P = 0.002), PLR ≤ 166 (P = 0.006, P = 0.016), CRP ≤ 12.5 (P = 0.001, P = 0.008), CEA (P 37 (P = 0.003), and a CRP > 12.5 (P = 0.013). A higher peritoneal cancer index (PCI > 24) was associated with elevation in CEA > 12, CA125 > 39, CA199 > 37, PLR > 166 and CRP > 12. The tumor histologic subtype was associated with CA 199 levels. The results from this investigation suggest that preoperative inflammatory markers in blood and serologic tumor markers may predict outcomes and are associated with tumor biology in patients with epithelial appendiceal neoplasm undergoing cytoreduction and intraperitoneal chemotherapy treatment.

Management of extramedullary plasmacytoma: Role of radiotherapy and prognostic factor analysis in 55 patients.

Science.gov (United States)

Wen, Ge; Wang, Weihu; Zhang, Yujing; Niu, Shaoqing; Li, Qiwen; Li, Yexiong

2017-10-01

To investigate potential prognostic factors affecting patient outcomes and to evaluate the optimal methods and effects of radiotherapy (RT) in the management of extramedullary plasmacytoma (EMP). Data from 55 patients with EMP between November 1999 and August 2015 were collected. The median age was 51 (range, 22-77) years. The median tumor size was 3.5 (range, 1.0-15.0) cm. The median applied dose was 50.0 (range, 30.0-70.0) Gy. Thirty-nine patients (70.9%) presented with disease in the head or neck region. Twelve patients received RT alone, 9 received surgery (S) alone, 3 received chemotherapy (CT) alone, and 3 patients did not receive any treatment. Combination therapies were applied in 28 patients. The median follow-up duration was 56 months. The 5-year local recurrence-free survival (LRFS), multiple myeloma-free survival (MMFS), progression-free survival (PFS) and overall survival (OS) rates were 79.8%, 78.6%, 65.2% and 76.0%, respectively. Univariate analysis revealed that RT was a favourable factor for all examined endpoints. Furthermore, head and neck EMPs were associated with superior LRFS, MMFS and PFS. Tumor size <4 cm was associated with superior MMFS, PFS and OS; serum M protein negativity was associated with superior MMFS and PFS; age ≥50 years and local recurrence were associated with poor MMFS. The dose ≥45 Gy group exhibited superior 5-year LRFS, MMFS and PFS rates (94.7%, 94.4%, 90.0%, respectively), while the corresponding values for the dose <45 Gy group were 62.5% (P=0.008), 53.3% (P=0.036) and 41.7% (P<0.001). Involved-site RT of at least 45 Gy should be considered for EMP. Furthermore, patients with head and neck EMP, tumor size <4 cm, age <50 years and serum M protein negativity had better outcomes.

The maximum standardized uptake value of 18 F-FDG PET scan to determine prognosis of hormone-receptor positive metastatic breast cancer

International Nuclear Information System (INIS)

Zhang, Jian; Hu, Xi-Chun; Jia, Zhen; Ragaz, Joseph; Zhang, Ying-Jian; Zhou, Min; Zhang, Yong-Ping; Li, Gang; Wang, Bi-Yun; Wang, Zhong-Hua

2013-01-01

Whether PET scan maximum standard uptake value (SUVmax) could differentiate luminal A from luminal B and help predict the survival of metastatic breast cancer (MBC) patients with luminal subtype is still unknown and need to be investigated. 305 MBC patients with luminal subtypes were screened with PET/CT. Eligible patients were prospectively followed up. In total, 134 patients were eligible for this study. SUVmax was significantly related to the number of metastatic sites and presence of visceral metastasis on univariate analysis. SUVmax could not effectively differentiate patients with luminal A from luminal B subtype. Although luminal subtype at diagnosis could predict the relapse-free interval, it could not predict progression-free survival (PFS) or overall survival (OS) after developing relapse. In contrast, SUVmax was predictive of both PFS and OS and this effect was maintained in multivariate COX regression model. SUVmax of MBC did not correlate with molecular subtypes of primary tumor. While molecular subtype may be a valuable prognostic factor at primary diagnosis of breast cancer, the SUVmax, rather than molecular subtype, does have a potential to predict independently in multivariate analysis for the PFS and OS in patients with metastatic disease of luminal subtype

Prognostic Significance of Blood Transfusion in Newly Diagnosed Multiple Myeloma Patients without Autologous Hematopoietic Stem Cell Transplantation

Science.gov (United States)

Fan, Liping; Fu, Danhui; Zhang, Jinping; Wang, Qingqing; Ye, Yamei; Xie, Qianling

2017-01-01

The aim of this study was to evaluate whether blood transfusions affect overall survival (OS) and progression-free survival (PFS) in newly diagnosed multiple myeloma (MM) patients without hematopoietic stem cell transplantation. A total of 181 patients were enrolled and divided into two groups: 68 patients in the transfused group and 113 patients in the nontransfused group. Statistical analyses showed that there were significant differences in ECOG scoring, Ig isotype, platelet (Plt) counts, hemoglobin (Hb) level, serum creatinine (Scr) level, and β2-microglobulin (β2-MG) level between the two groups. Univariate analyses showed that higher International Staging System staging, Plt counts blood transfusion was associated with PFS but not OS in MM patients. Multivariate analyses showed that blood transfusion was not an independent factor for PFS in MM patients. Our preliminary results suggested that newly diagnosed MM patients may benefit from a liberal blood transfusion strategy, since blood transfusion is not an independent impact factor for survival. PMID:28567420

Tip-surface interactions at redox responsive poly(ferrocenylsilane) (PFS) interface by AFM-based force spectroscopy

International Nuclear Information System (INIS)

Chung Hongjing; Song Jing; Vancso, G. Julius

2009-01-01

Poly(ferrocenylsilanes) (PFS) belong to the class of redox responsive organometallic polymers. Atomic force microscopy (AFM)-based single molecule force spectroscopy (SMFS) was used earlier to study single chain PFS response and redox energy driven single chain PFS molecular motors. Here we present further AFM investigations of force interactions between tip and a grafted PFS surface under potential control in electrochemical redox cycles. Typical tip-Au interaction is considered as reference in the force measurements. First the electrostatic component in the diffused double layer (DL) in NaClO 4 electrolyte environment was considered for a 'grafted to' PFS, which dominated the interplay between the tip and sample surface. The DL forces can also hinder the physisorption of PFS chain onto the tip when the voltage was applied at -0.1 V. On the other hand, if the tip contacted the PFS surface prior to the electrochemical process, physisorption of PFS chains governed the overall interaction regardless of subsequently applied surface potential. In addition, prolonged contact time, t c , may also contribute to the stability of tip-PFS bridging and detection of electrostatic forces between the tip-PFS interface. The results showed that tip-substrate interaction forces without PFS grafts have negligibly small force contributions under similar, electrochemically controlled, conditions used in single PFS chain based molecular motors.

Correlating tumor metabolic progression index measured by serial FDG PET-CT, apparent diffusion coefficient measured by magnetic resonance imaging (MRI) and blood genomics to patient’s outcome in advanced colorectal cancer: the CORIOLAN study

International Nuclear Information System (INIS)

Deleporte, Amelie; Charette, Nicolas; Machiels, Godelieve; Piccart, Martine; Flamen, Patrick; Hendlisz, Alain; Paesmans, Marianne; Garcia, Camilo; Vandeputte, Caroline; Lemort, Marc; Engelholm, Jean-Luc; Hoerner, Frederic; Aftimos, Philippe; Awada, Ahmad

2014-01-01

Metastatic colorectal cancer (mCRC) may present various behaviours that define different courses of tumor evolution. There is presently no available tool designed to assess tumor aggressiveness, despite the fact that this is considered to have a major impact on patient outcome. CORIOLAN is a single-arm prospective interventional non-therapeutic study aiming mainly to assess the natural tumor metabolic progression index (TMPI) measured by serial FDG PET-CT without any intercurrent antitumor therapy as a prognostic factor for overall survival (OS) in patients with mCRC. Secondary objectives of the study aim to test the TMPI as a prognostic marker for progression-free survival (PFS), to assess the prognostic value of baseline tumor FDG uptake on PFS and OS, to compare TMPI to classical clinico-biological assessment of prognosis, and to test the prognostic value on OS and PFS of MRI-based apparent diffusion coefficient (ADC) and variation of vADC using voxel-based diffusion maps. Additionally, this study intends to identify genomic and epigenetic factors that correlate with progression of tumors and the OS of patients with mCRC. Consequently, this analysis will provide information about the signaling pathways that determine the natural and therapy-free course of the disease. Finally, it would be of great interest to investigate whether in a population of patients with mCRC, for which at present no known effective therapy is available, tumor aggressiveness is related to elevated levels of circulating tumor cells (CTCs) and to patient outcome. Tumor aggressiveness is one of the major determinants of patient outcome in advanced disease. Despite its importance, supported by findings reported in the literature of extreme outcomes for patients with mCRC treated with chemotherapy, no objective tool allows clinicians to base treatment decisions on this factor. The CORIOLAN study will characterize TMPI using FDG-PET-based metabolic imaging of patients with chemorefractory m

The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma

International Nuclear Information System (INIS)

Liu, Li-Ting; Tang, Lin-Quan; Chen, Qiu-Yan; Zhang, Lu; Guo, Shan-Shan; Guo, Ling; Mo, Hao-Yuan; Zhao, Chong; Guo, Xiang; Cao, Ka-Jia; Qian, Chao-Nan; Zeng, Mu-Sheng; Bei, Jin-Xin; Hong, Ming-Huang; Shao, Jian-Yong; Sun, Ying; Ma, Jun; Mai, Hai-Qiang

2015-01-01

Purpose: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). Patients and Methods: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse–free survival (LRFS) and distant metastasis–free survival (DMFS). Results: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels after NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). Conclusion: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.

The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma

Energy Technology Data Exchange (ETDEWEB)

Liu, Li-Ting; Tang, Lin-Quan; Chen, Qiu-Yan; Zhang, Lu; Guo, Shan-Shan; Guo, Ling; Mo, Hao-Yuan; Zhao, Chong; Guo, Xiang; Cao, Ka-Jia; Qian, Chao-Nan [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China (China); Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou (China); Zeng, Mu-Sheng; Bei, Jin-Xin [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China (China); Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Hong, Ming-Huang [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China (China); Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Good Clinical Practice Center, Sun Yat-sen University Cancer Center, Guangzhou (China); Shao, Jian-Yong [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China (China); Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou (China); Sun, Ying; Ma, Jun [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China (China); Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou (China); Mai, Hai-Qiang, E-mail: maihq@sysucc.org.cn [Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China (China); Collaborative Innovation Center for Cancer Medicine, Guangzhou (China); Department of Nasopharyngeal Carcinoma, Sun Yat-sen University Cancer Center, Guangzhou (China)

2015-11-15

Purpose: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). Patients and Methods: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse–free survival (LRFS) and distant metastasis–free survival (DMFS). Results: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels after NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). Conclusion: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.

AR-V7 in circulating tumor cells cluster as a predictive biomarker of abiraterone acetate and enzalutamide treatment in castration-resistant prostate cancer patients.

Science.gov (United States)

Okegawa, Takatsugu; Ninomiya, Naoki; Masuda, Kazuki; Nakamura, Yu; Tambo, Mitsuhiro; Nutahara, Kikuo

2018-06-01

We examined whether androgen receptor splice variant 7 (AR-V7) in circulating tumor cell(CTC)clusters can be used to predict survival in patients with bone metastatic castration resistant-prostate cancer (mCRPC) treated with abiraterone or enzalutamide. We retrospectively enrolled 98 patients with CRPC on abiraterone or enzalutamide, and investigated the prognostic value of CTC cluster detection (+ v -) and AR-V7 detection (+ v -) using a CTC cluster detection - based AR-V7 mRNA assay. We examined ≤50% prostate-specific antigen (PSA) responses, PSA progression-free survival (PSA-PFS), clinical and radiological progression-free survival (radiologic PSF), and overall survival (OS). We then assessed whether AR-V7 expression in CTC clusters identified after On-chip multi-imaging flow cytometry was related to disease progression and survival after first-line systemic therapy. All abiraterone-treated or enzalutamide-treated patients received prior docetaxel. The median follow-up was 20.7 (range: 3.0-37.0) months in the abiraterone and enzalutamide cohorts, respectively. Forty-nine of the 98 men (50.0%) were CTC cluster (-), 23 of the 98 men (23.5%) were CTC cluster(+)/AR-V7(-), and 26 of the 98 men (26.5%) were CTC cluster(+)/AR-V7(+). CTC cluster(+)/AR-V7(+) patients were more likely to have EOD ≥3 at diagnosis (P = 0.003), pain (P = 0.023), higher alkaline phosphatase levels (P cluster(+), CTC cluster(+)/AR-V7(-), and ALP >UNL were independently associated with a poor PSA-PFS, radiographic PFS, and OS in abiraterone-treated patients and enzalutamide-treated patients. The CTC clusters and AR-V7-positive CTC clusters detected were important for assessing the response to abiraterone or enzalutamide therapy and for predicting disease outcome. © 2018 Wiley Periodicals, Inc.

Bevacizumab plus octreotide and metronomic capecitabine in patients with metastatic well-to-moderately differentiated neuroendocrine tumors: the xelbevoct study

International Nuclear Information System (INIS)

Berruti, Alfredo; D’Avolio, Antonio; Priola, Adriano Massimiliano; Birocco, Nadia; Amoroso, Vito; Biasco, Guido; Papotti, Mauro; Dogliotti, Luigi; Fazio, Nicola; Ferrero, Anna; Brizzi, Maria Pia; Volante, Marco; Nobili, Elisabetta; Tozzi, Lucia; Bodei, Lisa; Torta, Mirella

2014-01-01

We assessed the activity and toxicity of the XELBEVOCT regimen in patients with metastatic well-to-moderately differentiated neuroendocrine neoplasms (WMD-NEN). Ancillary studies evaluated hypertension, proteinuria, and vascular endothelial growth factor (VEGF) polymorphisms in predicting progression-free survival (PFS) and the predictive role of serum vitamin D in progression-free survival and proteinuria onset. This prospective phase 2 study included 45 patients with WMD-NEN arising from various primary sites. The treatment regimen was octreotide long-acting release (LAR), 20 mg monthly, metronomic capecitabine, 2000 mg/daily, and intravenous bevacizumab, 5 mg/kg every 2 weeks, without interruption for 9 months. Bevacizumab was continued until disease progression. Partial response was obtained in 8 patients (17.8%, 95% confidence interval [CI], 6.4%-28.2%); tumor response was more frequent in pancreatic than in non-pancreatic malignancies. The median PFS was 14.9 months; median overall survival was not attained. Biochemical and symptomatic responses were observed in 52.9% and 82.3% of cases, respectively. The treatment was well tolerated. Grade 3 toxicities included hand and foot syndrome (11.1%), proteinuria (4.4%), and renal toxicity (2.2%). Proteinuria (all grades) was correlated with longer PFS (p = 0.017). There was an inverse relationship between proteinuria and vitamin D levels. VEGF polymorphisms were not associated with patient outcome. The XELBEVOCT regimen is active and well tolerated in patients with metastatic WMD-NEN. Proteinuria correlated with hypovitaminosis D status and was the best predictive factor of treatment efficacy. Trial registration number http://www.clinicaltrials.gov/ct2/show/NCT01203306?term

Sorafenib and everolimus for patients with unresectable high-grade osteosarcoma progressing after standard treatment: a non-randomised phase 2 clinical trial.

Science.gov (United States)

Grignani, Giovanni; Palmerini, Emanuela; Ferraresi, Virginia; D'Ambrosio, Lorenzo; Bertulli, Rossella; Asaftei, Sebastian Dorin; Tamburini, Angela; Pignochino, Ymera; Sangiolo, Dario; Marchesi, Emanuela; Capozzi, Federica; Biagini, Roberto; Gambarotti, Marco; Fagioli, Franca; Casali, Paolo Giovanni; Picci, Piero; Ferrari, Stefano; Aglietta, Massimo

2015-01-01

Results of previous study showed promising but short-lived activity of sorafenib in the treatment of patients with unresectable advanced and metastatic osteosarcoma. This treatment failure has been attributed to the mTOR pathway and might therefore be overcome with the addition of mTOR inhibitors. We aimed to investigate the activity of sorafenib in combination with everolimus in patients with inoperable high-grade osteosarcoma progressing after standard treatment. We did this non-randomised phase 2 trial in three Italian Sarcoma Group centres. We enrolled adults (≥18 years) with relapsed or unresectable osteosarcoma progressing after standard treatment (methotrexate, cisplatin, and doxorubicin, with or without ifosfamide). Patients received 800 mg sorafenib plus 5 mg everolimus once a day until disease progression or unacceptable toxic effects. The primary endpoint was 6 month progression-free survival (PFS). All analyses were intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01804374. We enrolled 38 patients between June 16, 2011, and June 4, 2013. 17 (45%; 95% CI 28-61) of 38 patients were progression free at 6 months. Toxic effects led to dose reductions, or short interruptions, or both in 25 (66%) of 38 patients and permanent discontinuation for two (5%) patients. The most common grade 3-4 adverse events were lymphopenia and hypophosphataemia each in six (16%) patients, hand and foot syndrome in five (13%), thrombocytopenia in four (11%), and fatigue, oral mucositis, diarrhoea, and anaemia each in two (5%). One patient (3%) had a grade 3 pneumothorax that required trans-thoracic drainage, and that recurred at the time of disease progression. This was reported as a serious adverse event related to the study drugs in both instances. No other serious adverse events were reported during the trial. There were no treatment-related deaths. Although the combination of sorafenib and everolimus showed activity as a further-line treatment

Polyfluorinated surfactants (PFS) in paper and board coatings for food packaging

DEFF Research Database (Denmark)

Trier, Xenia; Granby, Kit; Christensen, Jan H

2011-01-01

sulfonamide N-alkyl esters were analysed. Di- and trialkylated PAPS and S-diPAPS were found in migrates from European food contact materials. Conclusion This study highlights the need to monitor for more types of PFS in order to map the sources of PFAS in humans and the environment.......range of polyfluorinated surfactants (PFS) used for food contact materials, primarily to impart oil and water repellency on paper and board. PFS are of interest, as they can be precursors of poly- and perfluorinated alkyl substances (PFAS), of which several are persistent and are found worldwide...... in human blood and in the environment. Materials and methods To determine the elemental composition of PFS, we combined information from patents, chemical suppliers and analyses of industrial blends using ultra performance liquid chromatography-negative electrospray ionisation quadrupole time...

Are pretreatment 18F-FDG PET tumor textural features in non-small cell lung cancer associated with response and survival after chemoradiotherapy?

Science.gov (United States)

Cook, Gary J R; Yip, Connie; Siddique, Muhammad; Goh, Vicky; Chicklore, Sugama; Roy, Arunabha; Marsden, Paul; Ahmad, Shahreen; Landau, David

2013-01-01

There is evidence in some solid tumors that textural features of tumoral uptake in (18)F-FDG PET images are associated with response to chemoradiotherapy and survival. We have investigated whether a similar relationship exists in non-small cell lung cancer (NSCLC). Fifty-three patients (mean age, 65.8 y; 31 men, 22 women) with NSCLC treated with chemoradiotherapy underwent pretreatment (18)F-FDG PET/CT scans. Response was assessed by CT Response Evaluation Criteria in Solid Tumors (RECIST) at 12 wk. Overall survival (OS), progression-free survival (PFS), and local PFS (LPFS) were recorded. Primary tumor texture was measured by the parameters coarseness, contrast, busyness, and complexity. The following parameters were also derived from the PET data: primary tumor standardized uptake values (SUVs) (mean SUV, maximum SUV, and peak SUV), metabolic tumor volume, and total lesion glycolysis. Compared with nonresponders, RECIST responders showed lower coarseness (mean, 0.012 vs. 0.027; P = 0.004) and higher contrast (mean, 0.11 vs. 0.044; P = 0.002) and busyness (mean, 0.76 vs. 0.37; P = 0.027). Neither complexity nor any of the SUV parameters predicted RECIST response. By Kaplan-Meier analysis, OS, PFS, and LPFS were lower in patients with high primary tumor coarseness (median, 21.1 mo vs. not reached, P = 0.003; 12.6 vs. 25.8 mo, P = 0.002; and 12.9 vs. 20.5 mo, P = 0.016, respectively). Tumor coarseness was an independent predictor of OS on multivariable analysis. Contrast and busyness did not show significant associations with OS (P = 0.075 and 0.059, respectively), but PFS and LPFS were longer in patients with high levels of each (for contrast: median of 20.5 vs. 12.6 mo, P = 0.015, and median not reached vs. 24 mo, P = 0.02; and for busyness: median of 20.5 vs. 12.6 mo, P = 0.01, and median not reached vs. 24 mo, P = 0.006). Neither complexity nor any of the SUV parameters showed significant associations with the survival parameters. In NSCLC, baseline (18)F

Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors.

Science.gov (United States)

Brabander, Tessa; van der Zwan, Wouter A; Teunissen, Jaap J M; Kam, Boen L R; Feelders, Richard A; de Herder, Wouter W; van Eijck, Casper H J; Franssen, Gaston J H; Krenning, Eric P; Kwekkeboom, Dik J

2017-08-15

Purpose: Bronchial and gastroenteropancreatic neuroendocrine tumors (NET) are slow-growing tumors, which frequently express somatostatin receptors on their cell membranes. These receptors are targets for therapy with Lutetium-177-labeled somatostatin analogues. We have treated over 1,200 patients with peptide receptor radionuclide therapy (PRRT) with [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate ( 177 Lu-DOTATATE) since the year 2000 and present the results on efficacy, survival, and toxicity of this therapy. Experimental Design: For safety analysis, 610 patients treated with a cumulative dose of at least 100 mCi (3.7 GBq) 177 Lu-DOTATATE were included. A subgroup of 443 Dutch patients who were treated with a cumulative dose of at least 600 mCi (22.2 GBq) 177 Lu-DOTATATE before 2013 was further analyzed for efficacy and survival. Results: The objective response rate of the total group of patients was 39%. Stable disease was reached in 43% of patients. Progression-free survival (PFS) and overall survival (OS) for all NET patients were 29 months [95% confidence interval (CI), 26-33 months] and 63 months (95% CI, 55-72 months). Long-term toxicity included acute leukemia in four patients (0.7%) and myelodysplastic syndrome in nine patients (1.5%). No therapy-related long-term renal or hepatic failure occurred. Conclusions: PRRT with 177 Lu-DOTATATE is a favorable therapeutic option in patients with metastatic bronchial and gastroenteropancreatic NETs that express somatostatin receptors. PRRT with 177 Lu-DOTATATE is safe with few side-effects and shows good response rates with PFS of 29 months and OS of 63 months. Clin Cancer Res; 23(16); 4617-24. ©2017 AACR . ©2017 American Association for Cancer Research.

Randomized Phase III Trial of Trastuzumab Plus Capecitabine With or Without Pertuzumab in Patients With Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer Who Experienced Disease Progression During or After Trastuzumab-Based Therapy.

Science.gov (United States)

Urruticoechea, Ander; Rizwanullah, Mohammed; Im, Seock-Ah; Ruiz, Antonio Carlos Sánchez; Láng, István; Tomasello, Gianluca; Douthwaite, Hannah; Badovinac Crnjevic, Tanja; Heeson, Sarah; Eng-Wong, Jennifer; Muñoz, Montserrat

2017-09-10

Purpose To assess the efficacy and safety of trastuzumab plus capecitabine with or without pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer who experienced disease progression during or after trastuzumab-based therapy and received a prior taxane. Patients and Methods Patients were randomly assigned to arm A: trastuzumab 8 mg/kg → 6 mg/kg once every 3 weeks plus capecitabine 1,250 mg/m 2 twice a day (2 weeks on, 1 week off, every 3 weeks); or arm B: pertuzumab 840 mg → 420 mg once every 3 weeks plus trastuzumab at the same dose and schedule as arm A plus capecitabine 1,000 mg/m 2 on the same schedule as arm A. The primary end point was independent review facility-assessed progression-free survival (IRF PFS). Secondary end points included overall survival (OS) and safety. Hierarchical testing procedures were used to control type I error for statistical testing of IRF PFS, OS, and objective response rate. Results Randomly assigned (intent-to-treat) populations were 224 and 228 patients in arms A and B, respectively. Median IRF PFS at 28.6 and 25.3 months' median follow-up was 9.0 v 11.1 months (hazard ratio, 0.82; 95% CI, 0.65 to 1.02; P = .0731) and interim OS was 28.1 v 36.1 months (hazard ratio, 0.68; 95% CI, 0.51 to 0.90). The most common adverse events (all grades; incidence of ≥ 10% in either arm and ≥ 5% difference between arms) were hand-foot syndrome, nausea, and neutropenia in arm A, and diarrhea, rash, and nasopharyngitis in arm B. Conclusion The addition of pertuzumab to trastuzumab and capecitabine did not significantly improve IRF PFS. An 8-month increase in median OS to 36.1 months with pertuzumab was observed. Statistical significance for OS cannot be claimed because of the hierarchical testing of OS after the primary PFS end point; however, the magnitude of OS difference is in keeping with prior experience of pertuzumab in metastatic breast cancer. No new safety signals were identified.

REGOSARC: Regorafenib versus placebo in doxorubicin-refractory soft-tissue sarcoma-A quality-adjusted time without symptoms of progression or toxicity analysis.

Science.gov (United States)

Berry, Vincent; Basson, Laurent; Bogart, Emilie; Mir, Olivier; Blay, Jean-Yves; Italiano, Antoine; Bertucci, François; Chevreau, Christine; Clisant-Delaine, Stéphanie; Liegl-Antzager, Bernadette; Tresch-Bruneel, Emmanuelle; Wallet, Jennifer; Taieb, Sophie; Decoupigny, Emilie; Le Cesne, Axel; Brodowicz, Thomas; Penel, Nicolas

2017-06-15

In a placebo-controlled, randomized phase 2 trial (ClinicalTrials.gov identifier NCT01900743), regorafenib improved progression-free survival (PFS) for patients with doxorubicin-pretreated advanced nonadipocytic sarcoma. A quality-adjusted time without symptoms of progression or toxicity (Q-TWiST) post hoc exploratory analysis was applied to provide an integrated measure of its clinical benefit. In the base-case analysis, each patient's overall survival (OS) was partitioned into 3 mutually exclusive health states: the time with a grade 3 or 4 adverse event (TOX), the time without symptoms of disease or grade 3 or 4 toxicity from treatment, and the time after tumor progression or relapse. The time spent in each state was weighted with a health-state utility associated with that state and was summed to calculate the Q-TWiST. The stability of the base-case analysis was explored with several sensitivity analyses. In nonadipocytic sarcoma, the PFS was (4.0 months [2.6-5.5 months] with regorafenib vs 1.0 month [0.9-1.8 months] with a placebo; hazard ratio, 0.36 [0.25-0.53]; P regorafenib and 9.0 months (6.8-12.5 months) with a placebo (hazard ratio, 0.67 [0.44-1.02]). With the classic definition of TOX (including all grade 3 and 4 clinical adverse events), the Q-TWiSTs were 8.0 months (7.0-9.0 months) with regorafenib and 5.7 months (4.9-6.4 months) with a placebo (P regorafenib significantly improved quality-adjusted survival in comparison with a placebo. Cancer 2017;123:2294-2302. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. © 2017 American Cancer Society.

A plant-produced Pfs230 vaccine candidate blocks transmission of Plasmodium falciparum.

Science.gov (United States)

Farrance, Christine E; Rhee, Amy; Jones, R Mark; Musiychuk, Konstantin; Shamloul, Moneim; Sharma, Satish; Mett, Vadim; Chichester, Jessica A; Streatfield, Stephen J; Roeffen, Will; van de Vegte-Bolmer, Marga; Sauerwein, Robert W; Tsuboi, Takafumi; Muratova, Olga V; Wu, Yimin; Yusibov, Vidadi

2011-08-01

Plasmodium falciparum is transmitted to a new host after completing its sexual cycle within a mosquito. Developing vaccines against the parasite sexual stages is a critical component in the fight against malaria. We are targeting multiple proteins of P. falciparum which are found only on the surfaces of the sexual forms of the parasite and where antibodies against these proteins have been shown to block the progression of the parasite's life cycle in the mosquito and thus block transmission to the next human host. We have successfully produced a region of the Pfs230 antigen in our plant-based transient-expression system and evaluated this vaccine candidate in an animal model. This plant-produced protein, 230CMB, is expressed at approximately 800 mg/kg in fresh whole leaf tissue and is 100% soluble. Administration of 230CMB with >90% purity induces strong immune responses in rabbits with high titers of transmission-blocking antibodies, resulting in a greater than 99% reduction in oocyst counts in the presence of complement, as determined by a standard membrane feeding assay. Our data provide a clear perspective on the clinical development of a Pfs230-based transmission-blocking malaria vaccine.

When Progressive Disease Does Not Mean Treatment Failure: Reconsidering the Criteria for Progression

Science.gov (United States)

2012-01-01

Although progression-based endpoints, such as progression-free survival, are often key clinical trial endpoints for anticancer agents, the clinical meaning of “objective progression” is much less certain. As scrutiny of progression-based endpoints in clinical trials increases, it should be remembered that the Response Evaluation Criteria In Solid Tumors (RECIST) progression criteria were not developed as a surrogate for survival. Now that progression-free survival has come to be an increasingly important trial endpoint, the criteria that define progression deserve critical evaluation to determine whether alternate definitions of progression might facilitate the development of stronger surrogate endpoints and more meaningful trial results. In this commentary, we review the genesis of the criteria for progression, highlight recent data that question their value as a marker of treatment failure, and advocate for several research strategies that could lay the groundwork for a clinically validated definition of disease progression in solid tumor oncology. PMID:22927506

Comparison of Alternative Androgen Receptor-axis-targeted Agent (ARATA) and Docetaxel as Second-line Therapy for Patients With Metastatic Castration-resistant Prostate Cancer With Progression After Initial ARATA in Real-world Clinical Practice in Japan.

Science.gov (United States)

Miyake, Hideaki; Sugiyama, Takayuki; Aki, Ryota; Matsushita, Yuto; Tamura, Keita; Motoyama, Daisuke; Ito, Toshiki; Otsuka, Atsushi

2018-06-01

The objective of the present study was to assess the oncologic outcomes of patients receiving second-line therapy against metastatic castration-resistant prostate cancer (mCRPC). The present study included 222 consecutive mCRPC patients with progression during initial androgen receptor-axis-targeted agent (ARATA) therapy with either abiraterone acetate (AA) or enzalutamide (Enz). Of these 222 patients, 108 subsequently received an alternative ARATA (AA-to-Enz, n = 49; Enz-to-AA, n = 59) and 114 received docetaxel (DTX; AA-to-DTX, n = 54; Enz-to-DTX, n = 60). The prostate-specific antigen (PSA) level in the 114 patients receiving DTX was significantly greater than that in the 108 patients receiving ARATA. However, no significant differences were found in the remaining parameters between the 2 groups. The PSA response rate, PSA progression-free survival (PFS), and overall survival (OS) during second-line therapy in the DTX group (n = 114) were significantly superior to those for the ARATA group (n = 108; PSA response rate, 42.1% vs. 21.3%; median PSA PFS, 7.2 vs. 4.2 months; median OS, 17.5 vs. 14.5 months). Similar trends were confirmed by comparing these outcomes among 4 therapy groups, with significant differences (PSA response rate, Enz-to-AA vs. AA-to-DTX and Enz-to-AA vs. Enz-to-DTX; PSA PFS, AA-to-Enz vs. Enz-to-AA, AA-to-Enz vs. AA-to-DTX, Enz-to-AA vs. AA-to-DTX, and Enz-to-AA vs. Enz-to-DTX; and OS, Enz-to-AA vs. AA-to-DTX and Enz-to-AA vs. Enz-to-DTX). Furthermore, the introduction of DTX was independently associated with improved PSA PFS, but not OS, on multivariate analysis. Favorable oncologic outcomes can be expected with DTX treatment, rather than with alternative ARATA, for mCRPC patients after failure of an initial ARATA. Copyright © 2017 Elsevier Inc. All rights reserved.

Real world data on young patients with high-risk diffuse large B-cell lymphoma treated with R-CHOP or R-CHOEP - MYC, BCL2 and BCL6 as prognostic biomarkers

DEFF Research Database (Denmark)

Pedersen, Mette Ølgod; Gang, Anne Ortved; Brown, Peter

2017-01-01

BACKGROUND: Double expression of MYC and BCL2 proteins (DE) and double-hit MYC+BCL2/BCL6 translocations (DH) were established as important biomarkers in patients with diffuse large B-cell lymphoma (DLBCL) by the 2016 revision of the World Health Organization classification of lymphoid neoplasms...... in situ hybridization (FISH). RESULTS: DE with MYC>75% and BCL2>85% was an independent negative prognostic marker of progression free survival (PFS) in patients treated with R-CHOP but not R-CHOEP (peffect of DE for response (PFS) to R...

Design and endpoints of clinical and translational trials in advanced colorectal cancer. a proposal from GROUP Español Multidisciplinar en Cancer Digestivo (GEMCAD).

Science.gov (United States)

Carrera, Gemma; Garcia-Albeniz, Xabier; Ayuso, Juan Ramón; Aparicio, Jorge; Castells, Antoni; Codony-Servat, Jordi; Feliu, Jaime; Fuster, David; Gallego, Rosa; Pagés, Mario; Torres, Ferran; Maurel, Joan

2011-05-01

Meta-analytic reviews of Randomized Clinical Trials (RCT) have reached contradictory conclusions regarding the benefit of medical interventions in Advanced Colorectal Cancer (ACRC). Surrogate markers of survival benefit, such as response rate (RR) and progression free-survival (PFS) often show contradictory and highly variable correlations. These contradictions can be due to differences in 1) the studies analysed (sources), 2) the quality of clinical trials (intrinsic bias in the design, biased data analysis, heterogeneous PFS definitions) and 3) the second-line strategies between arms. PFS is a more vulnerable target than overall survival (OS), but the latter can also be affected by different biases and additional medical interventions such as secondary resection of metastases or second-line therapies. Therefore the correlation between PFS and survival must be clearly stated if PFS is to be considered as a primary endpoint. Of the differences between studies, only the quality of clinical trials can be improved by a deeper knowledge of both the area of study (i.e. colorectal cancer) and the methodology needed (i.e., clinical and translational trials). The aim of this manuscript is to offer the basic resources to develop experimental trials in ACRC. To this end, techniques for diagnosis and for response assessment are discussed, prognostic factors and treatment standards are critically exposed, and notes about how to design useful translational studies are provided.

Carboplatin and pegylated liposomal doxorubicin versus carboplatin and paclitaxel in very platinum-sensitive ovarian cancer patients

DEFF Research Database (Denmark)

Mahner, Sven; Meier, Werner; du Bois, Andreas

2015-01-01

- and paclitaxel-based therapies. Patients were randomised to CD [carboplatin-pegylated liposomal doxorubicin (PLD)] or CP (carboplatin-paclitaxel) and stratified by treatment-free interval (TFI). In this analysis, patients with a TFI>24 months were analysed separately for progression free survival (PFS...... (8% versus 3.1%; P=0.082) sensory neuropathy (4.8% versus 2.3%; P=0.27) and grade 2 alopecia (88% versus 9.2%; P

Randomized, placebo-controlled, phase III trial of sunitinib plus prednisone versus prednisone alone in progressive, metastatic, castration-resistant prostate cancer.

Science.gov (United States)

Michaelson, M Dror; Oudard, Stephane; Ou, Yen-Chuan; Sengeløv, Lisa; Saad, Fred; Houede, Nadine; Ostler, Peter; Stenzl, Arnulf; Daugaard, Gedske; Jones, Robert; Laestadius, Fredrik; Ullèn, Anders; Bahl, Amit; Castellano, Daniel; Gschwend, Juergen; Maurina, Tristan; Chow Maneval, Edna; Wang, Shaw-Ling; Lechuga, Maria Jose; Paolini, Jolanda; Chen, Isan

2014-01-10

We evaluated angiogenesis-targeted sunitinib therapy in a randomized, double-blind trial of metastatic castration-resistant prostate cancer (mCRPC). Men with progressive mCRPC after docetaxel-based chemotherapy were randomly assigned 2:1 to receive sunitinib 37.5 mg/d continuously or placebo. Patients also received oral prednisone 5 mg twice daily. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS). Two interim analyses were planned. Overall, 873 patients were randomly assigned to receive sunitinib (n = 584) or placebo (n = 289). The independent data monitoring committee stopped the study for futility after the second interim analysis. After a median overall follow-up of 8.7 months, median OS was 13.1 months and 11.8 months for sunitinib and placebo, respectively (hazard ratio [HR], 0.914; 95% CI, 0.762 to 1.097; stratified log-rank test, P = .168). PFS was significantly improved in the sunitinib arm (median 5.6 v 4.1 months; HR, 0.725; 95% CI, 0.591 to 0.890; stratified log-rank test, P < .001). Toxicity and rates of discontinuations because of adverse events (AEs; 27% v 7%) were greater with sunitinib than placebo. The most common treatment-related grade 3/4 AEs were fatigue (9% v 1%), asthenia (8% v 2%), and hand-foot syndrome (7% v 0%). Frequent treatment-emergent grade 3/4 hematologic abnormalities were lymphopenia (20% v 11%), anemia (9% v 8%), and neutropenia (6% v < 1%). The addition of sunitinib to prednisone did not improve OS compared with placebo in docetaxel-refractory mCRPC. The role of antiangiogenic therapy in mCRPC remains investigational.

A randomized trial of diet and physical activity in women treated for stage II—IV ovarian cancer: Rationale and design of the Lifestyle Intervention for Ovarian Cancer Enhanced Survival (LIVES): An NRG Oncology/Gynecologic Oncology Group (GOG-225) Study☆,☆☆

Science.gov (United States)

Thomson, Cynthia A.; Crane, Tracy E.; Miller, Austin; Garcia, David O.; Basen-Engquist, Karen; Alberts, David S.

2016-01-01

Ovarian cancer is the most common cause of gynecological cancer death in United States women. Efforts to improve progression free survival (PFS) and quality of life (QoL) after treatment for ovarian cancer are necessary. Observational studies suggest that lifestyle behaviors, including diet and physical activity, are associated with lower mortality in this population. The Lifestyle Intervention for Ovarian Cancer Enhanced Survival (LIVES) NRG 0225 study is a randomized, controlled trial designed to test the hypothesis that a 24 month lifestyle intervention will significantly increase PFS after oncological therapy for stage II-IV ovarian cancer. Women are randomized 1:1 to a high vegetable and fiber, low-fat diet with daily physical activity goals or an attention control group. Secondary outcomes to be evaluated include QoL and gastrointestinal health. Moreover an a priori lifestyle adherence score will be used to evaluate relationships between adoption of the diet and activity goals and PFS. Blood specimens are collected at baseline, 6, 12 and 24 months for analysis of dietary adherence (carotenoids) in addition to mechanistic biomarkers (lipids, insulin, telomere length). Women are enrolled at NRG clinic sites nationally and the telephone based lifestyle intervention is delivered from The University of Arizona call center by trained health coaches. A study specific multi-modal telephone, email, and SMS behavior change software platform is utilized for information delivery, coaching and data capture. When completed, LIVES will be the largest behavior-based lifestyle intervention trial conducted among ovarian cancer survivors. PMID:27394382

Intravenous versus oral etoposide

DEFF Research Database (Denmark)

Ali, Abir Salwa; Grönberg, Malin; Langer, Seppo W.

2018-01-01

High-grade gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs, G3) are aggressive cancers of the digestive system with poor prognosis and survival. Platinum-based chemotherapy (cisplatin/carboplatin + etoposide) is considered the first-line palliative treatment. Etoposide is frequently...... administered intravenously; however, oral etoposide may be used as an alternative. Concerns for oral etoposide include decreased bioavailability, inter- and intra-patient variability and patient compliance. We aimed to evaluate possible differences in progression-free survival (PFS) and overall survival (OS......) in patients treated with oral etoposide compared to etoposide given as infusion. Patients (n = 236) from the Nordic NEC study were divided into three groups receiving etoposide as a long infusion (24 h, n = 170), short infusion (≤ 5 h, n = 33) or oral etoposide (n = 33) according to hospital tradition. PFS...

Prognostic factors for progression-free and overall survival in advanced biliary tract cancer

DEFF Research Database (Denmark)

Bridgewater, J; Lopes, A; Wasan, H

2016-01-01

independently with outcome. This score was validated externally by receiver operating curve (ROC) analysis using the independent international dataset. RESULTS: A total of 410 patients were included from the ABC-02 study and 753 from the international dataset. An overall survival (OS) and progression......BACKGROUND: Biliary tract cancer is an uncommon cancer with a poor outcome. We assembled data from the National Cancer Research Institute (UK) ABC-02 study and 10 international studies to determine prognostic outcome characteristics for patients with advanced disease. METHODS: Multivariable...... biliary tract cancer derived from the ABC-02 study that are validated in an international dataset. Although these findings establish the benchmark for the prognostic evaluation of patients with ABC and confirm the value of longheld clinical observations, the ability of the model to correctly predict...

Survival modeling for the estimation of transition probabilities in model-based economic evaluations in the absence of individual patient data: a tutorial.

Science.gov (United States)

Diaby, Vakaramoko; Adunlin, Georges; Montero, Alberto J

2014-02-01

Survival modeling techniques are increasingly being used as part of decision modeling for health economic evaluations. As many models are available, it is imperative for interested readers to know about the steps in selecting and using the most suitable ones. The objective of this paper is to propose a tutorial for the application of appropriate survival modeling techniques to estimate transition probabilities, for use in model-based economic evaluations, in the absence of individual patient data (IPD). An illustration of the use of the tutorial is provided based on the final progression-free survival (PFS) analysis of the BOLERO-2 trial in metastatic breast cancer (mBC). An algorithm was adopted from Guyot and colleagues, and was then run in the statistical package R to reconstruct IPD, based on the final PFS analysis of the BOLERO-2 trial. It should be emphasized that the reconstructed IPD represent an approximation of the original data. Afterwards, we fitted parametric models to the reconstructed IPD in the statistical package Stata. Both statistical and graphical tests were conducted to verify the relative and absolute validity of the findings. Finally, the equations for transition probabilities were derived using the general equation for transition probabilities used in model-based economic evaluations, and the parameters were estimated from fitted distributions. The results of the application of the tutorial suggest that the log-logistic model best fits the reconstructed data from the latest published Kaplan-Meier (KM) curves of the BOLERO-2 trial. Results from the regression analyses were confirmed graphically. An equation for transition probabilities was obtained for each arm of the BOLERO-2 trial. In this paper, a tutorial was proposed and used to estimate the transition probabilities for model-based economic evaluation, based on the results of the final PFS analysis of the BOLERO-2 trial in mBC. The results of our study can serve as a basis for any model

Efficacy and safety of SOX chemotherapy with or without surgery in AFP-producing advanced gastric cancer

OpenAIRE

Li, Zhu; Hou, Xu; Chen, Juan; Sun, Huidong; Mi, Yuetang; Sui, Yongling; Li, Yuhong; Xie, Jiaping; Qiao, Yingli; Lei, Xiaofeng; Che, Xiaoshuang; Liu, Jun

2017-01-01

The present study investigated the clinical efficacy of S-1 plus oxaliplatin (SOX) regimen, with or without surgery in ?-fetoprotein-producing gastric cancer (APGC) with liver metastasis. A total of 24 patients with APGC treated at the Liaocheng People's Hospital between January 2011 and December 2013 were retrospectively reviewed. Clinical efficacy and patient safety were compared between the two groups. The median progression-free survival (PFS) and overall survival (OS) in the SOX group we...

Whole brain irradiation with hippocampal sparing and dose escalation on multiple brain metastases. Local tumour control and survival

Energy Technology Data Exchange (ETDEWEB)

Oehlke, Oliver; Wucherpfennig, David; Prokic, Vesna [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); Fels, Franziska [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); St. Josefs Hospital, Department of Radiation Oncology, Offenburg (Germany); Frings, Lars [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); University Hospital Freiburg, Department of Geriatrics and Gerontology, Freiburg (Germany); University Medical Center Freiburg, Department of Nuclear Medicine, Freiburg (Germany); Egger, Karl [University Medical Center Freiburg, Department of Neuroradiology, Freiburg (Germany); Weyerbrock, Astrid [University Medical Center Freiburg, Department of Neurosurgery, Freiburg (Germany); Nieder, Carsten [Nordland Hospital, Department of Oncology and Palliative Medicine, Bodoe (Norway); University of Tromsoe, Institute of Clinical Medicine, Faculty of Health Sciences, Tromsoe (Norway); Grosu, Anca-Ligia [University Medical Center Freiburg, Department of Radiation Oncology, Freiburg (Germany); German Cancer Consortium (DKTK), Freiburg (Germany); German Cancer Research Center (DKFZ), Heidelberg (Germany)

2015-01-16

Hippocampal-avoidance whole brain radiotherapy (HA-WBRT) for multiple brain metastases may prevent treatment-related cognitive decline, compared to standard WBRT. Additionally, simultaneous integrated boost (SIB) on individual metastases may further improve the outcome. Here, we present initial data concerning local tumour control (LTC), intracranial progression-free survival (PFS), overall survival (OS), toxicity and safety for this new irradiation technique. Twenty patients, enrolled between 2011 and 2013, were treated with HA-WBRT (30 Gy in 12 fractions, D{sub 98} {sub %} to hippocampus ≤ 9 Gy) and a SIB (51 Gy) on multiple (2-13) metastases using a volumetric modulated arc therapy (VMAT) approach based on 2-4 arcs. Metastases were evaluated bidimensionally along the two largest diameters in contrast-enhanced three-dimensional T1-weighed MRI. Median follow-up was 40 weeks. The median time to progression of boosted metastases has not been reached yet, corresponding to a LTC rate of 73 %. Median intracranial PFS was 40 weeks, corresponding to a 1-year PFS of 45.3 %. Median OS was 71.5 weeks, corresponding to a 1-year OS of 60 %. No obvious acute or late toxicities grade > 2 (NCI CTCAE v4.03) were observed. D{sub mean} to the bilateral hippocampi was 6.585 Gy ± 0.847 (α/β = 2 Gy). Two patients developed a new metastasis in the area of hippocampal avoidance. HA-WBRT (simultaneous integrated protection, SIP) with SIB to metastases is a safe and tolerable regime that shows favorable LTC for patients with multiple brain metastases, while it has the potential to minimize the side-effect of cognitive deterioration. (orig.) [German] Die Hippocampus-schonende Ganzhirnbestrahlung (HS-GHB) kann im Vergleich zur Standard-GHB die Verschlechterung der neurokognitiven Funktion verhindern. Zusaetzlich vermag ein simultan integrierter Boost (SIB) auf die Metastasen die Prognose der betroffenen Patienten weiter zu verbessern. In dieser Studie praesentieren wir erste Ergebnisse

A Martian PFS average spectrum: Comparison with ISO SWS

Science.gov (United States)

Formisano, V.; Encrenaz, T.; Fonti, S.; Giuranna, M.; Grassi, D.; Hirsh, H.; Khatuntsev, I.; Ignatiev, N.; Lellouch, E.; Maturilli, A.; Moroz, V.; Orleanski, P.; Piccioni, G.; Rataj, M.; Saggin, B.; Zasova, L.

2005-08-01

The evaluation of the planetary Fourier spectrometer performance at Mars is presented by comparing an average spectrum with the ISO spectrum published by Lellouch et al. [2000. Planet. Space Sci. 48, 1393.]. First, the average conditions of Mars atmosphere are compared, then the mixing ratios of the major gases are evaluated. Major and minor bands of CO 2 are compared, from the point of view of features characteristics and bands depth. The spectral resolution is also compared using several solar lines. The result indicates that PFS radiance is valid to better than 1% in the wavenumber range 1800-4200 cm -1 for the average spectrum considered (1680 measurements). The PFS monochromatic transfer function generates an overshooting on the left-hand side of strong narrow lines (solar or atmospheric). The spectral resolution of PFS is of the order of 1.3 cm -1 or better. A large number of narrow features to be identified are discovered.

Venetoclax for patients with chronic lymphocytic leukemia who progressed during or after idelalisib therapy.

Science.gov (United States)

Coutre, Steven; Choi, Michael; Furman, Richard R; Eradat, Herbert; Heffner, Leonard; Jones, Jeffrey A; Chyla, Brenda; Zhou, Lang; Agarwal, Suresh; Waskiewicz, Tina; Verdugo, Maria; Humerickhouse, Rod A; Potluri, Jalaja; Wierda, William G; Davids, Matthew S

2018-04-12

B-cell receptor pathway inhibitors (BCRis) have transformed treatment of chronic lymphocytic leukemia (CLL); however, the efficacy of therapies for patients whose disease is refractory to/relapses after (R/R) BCRis is unknown. Venetoclax is a selective, orally bioavailable BCL-2 inhibitor with activity in patients with CLL, including those who are heavily pretreated or have 17p deletion. This phase 2 study prospectively evaluated venetoclax in patients with R/R CLL after ibrutinib or idelalisib; here we report on patients who received idelalisib as the last BCRi before enrollment. Venetoclax was initiated at 20 mg daily, followed by intrapatient ramp-up to 400 mg daily. Primary objectives included efficacy (objective response rate [ORR]) and safety of venetoclax. The study enrolled 36 patients who previously received idelalisib (ORR, 67% [24/36]); 2 patients achieved complete remission, and 1 had complete remission with incomplete bone marrow recovery. Median progression-free survival (PFS) has not yet been reached; estimated 12-month PFS was 79%. The most common adverse events (AEs; all grades) were neutropenia (56%), diarrhea (42%), upper respiratory tract infection (39%), thrombocytopenia (36%), nausea (31%), fatigue (28%), cough (22%), rash (22%), and anemia (22%). Grade 3 or 4 AEs were primarily hematologic (neutropenia [50%], thrombocytopenia [25%], and anemia [17%]). No patients experienced tumor lysis syndrome. Venetoclax demonstrated promising clinical activity and favorable tolerability in patients with CLL whose disease progressed during or after idelalisib therapy. This trial was registered at www.clinicaltrials.gov as #NCT02141282. © 2018 by The American Society of Hematology.

Impact of Weight Change During the Course of Concurrent Chemoradiation Therapy on Outcomes in Stage IIIB Non-Small Cell Lung Cancer Patients: Retrospective Analysis of 425 Patients

International Nuclear Information System (INIS)

Topkan, Erkan; Parlak, Cem; Selek, Ugur

2013-01-01

Purpose: We retrospectively investigated the impact of weight change (WC) during concurrent chemoradiation therapy (C-CRT) on clinical outcomes of stage 3B non-small cell lung cancer (NSCLC) patients. Methods and Materials: A total of 425 patients treated with C-CRT were included. All patients received 60 to 66 Gy of thoracic radiation therapy concurrently with 1 to 3 cycles of platinum-based chemotherapy. Pre- and posttreatment weight measurements on first and last days of C-CRT were used for WC. Patients were divided into 2 groups: group 1 = weight loss (WL); group 2 = weight preservation/gain (WP) for comparative analyses. Results: Following C-CRT, 252 patients (59.3%) experienced WL, while 89 patients (20.9%) and 84 patients (19.8%) showed WP or WG. At median 24.2 months of follow-up, 142 patients (33.4%) were alive (84 WP [48.6%] and 58 WL [23.0%]), and 58 (13.6%) of them were free of disease progression (41 [23.7%] for WP and 17 [6.7%] for WL). Median overall survival (OS), locoregional progression-free survival (LRPFS), progression-free survival (PFS), and distant metastases-free survival (DMFS) for the entire population were 22.8, 14.4, 10.6, and 11.7 months, respectively. Intergroup comparisons between WP and WL cohorts revealed significantly superior OS, LRPFS, PFS, and DMFS in WP patients (P<.05 for each). On multivariate analyses, only WL and advanced T stage were associated with poor prognosis (P<.05). Conclusions: Present results in 425 stage 3B NSCLC patients demonstrated that WL during C-CRT is strongly associated with inferior survival outcomes compared to WP. This emerging finding might be useful by forming an encouraging basis for future investigations in facilitating a way to improve the outcomes of these patients experiencing WL during C-CRT

Free Testosterone During Androgen Deprivation Therapy Predicts Castration-Resistant Progression Better Than Total Testosterone.

Science.gov (United States)

Regis, Lucas; Planas, Jacques; Carles, Joan; Maldonado, Xavier; Comas, Inma; Ferrer, Roser; Morote, Juan

2017-01-01

The optimal degree of testosterone suppression in patients with prostate cancer undergoing androgen deprivation therapy remains in question. Furthermore, serum free testosterone, which is the active form of testosterone, seems to correlate with intraprostatic testosterone. Here we compared free and total serum testosterone as predictors of survival free of castration resistance. Total testosterone (chemiluminescent assay, lower sensitivity 10 ng/dl) and free testosterone (analogue-ligand radioimmunoassay, lower sensitivity 0.05 pg/ml) were determined at 6 months of LHRH agonist treatment in a prospective cohort of 126 patients with prostate cancer. During a mean follow-up of 67 months (9-120), 75 (59.5%) events of castration-resistant progression were identified. Multivariate analysis and survival analysis according to total testosterone cutoffs of 50, 32, and 20 ng/dl, and free testosterone cutoffs of 1.7, 1.1, and 0.7 pg/ml were performed. Metastatic spread was the most powerful predictor of castration resistance, HR: 2.09 (95%CI: 1.18-3.72), P = 0.012. Gleason score, baseline PSA and PSA at 6 months were also independents predictors, but not free and total testosterone. Stratified analysis was conducted on the basis of the status of metastatic diseases and free testosterone was found to be an independent predictor of survival free of castration resistance in the subgroup of patients without metastasis, HR: 2.12 (95%CI: 1.16-3.85), P = 0.014. The lowest threshold of free testosterone which showed significant differences was 1.7 pg/ml, P = 0.003. Free testosterone at 6 months of LHRH agonist treatment seems to be a better surrogate than total testosterone to predict castration resistance in no metastatic prostate cancer patients. Prostate 77:114-120, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Erlotinib treatment in patients with advanced lung adenocarcinoma with CISH-positive and CISH-negative EGFR gene alterations.

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Hou, Ming-Mo; Huang, Shiu-Feng; Kuo, Han-Pin; Yang, Cheng-Ta; Tsai, Ying-Huang; Yu, Chih-Teng; Lin, Horng-Chyuan; Chen, Chih-Hung; Wang, Chih-Liang; Chung, Fu-Tsai; Hsieh, Jia-Juan; Hsu, Todd; Cheng, Hsin-Yi; Ou, Li-Ying; Wang, Hung-Ming; Lin, Yung-Chang; Chang, Nai-Jen; Chang, John Wen-Cheng

2012-03-01

Epidermal growth factor receptor (EGFR) positivity as assessed by chromogenic in situ hybridization (CISH) has been demonstrated to be associated with EGFR mutation status. This study was conducted to compare the responsiveness of CISH-positive and CISH-negative lung adenocarcinomas to erlotinib. Patients received erlotinib (150 mg/day) alone until disease progression or intolerable toxicity. EGFR gene status was examined by CISH. The response rate (RR), progression-free survival (PFS), overall survival (OS) and toxicity profiles were assessed. Thirty-one patients underwent response evaluations and CISH analyses, 12 of whom harboured CISH-positive adenocarcinomas. The overall RR (p=0.035), median PFS (p=0.091) and median OS (p=0.408) were higher in the CISH-positive group. No difference in toxicity profiles was observed between these two groups. EGFR status as assessed by CISH can predict the response to erlotinib in patients with advanced lung adenocarcinoma.

PfsR is a key regulator of iron homeostasis in Synechocystis PCC 6803.

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Dan Cheng

Full Text Available Iron is an essential cofactor in numerous cellular processes. The iron deficiency in the oceans affects the primary productivity of phytoplankton including cyanobacteria. In this study, we examined the function of PfsR, a TetR family transcriptional regulator, in iron homeostasis of the cyanobacterium Synechocystis PCC 6803. Compared with the wild type, the pfsR deletion mutant displayed stronger tolerance to iron limitation and accumulated significantly more chlorophyll a, carotenoid, and phycocyanin under iron-limiting conditions. The mutant also maintained more photosystem I and photosystem II complexes than the wild type after iron deprivation. In addition, the activities of photosystem I and photosystem II were much higher in pfsR deletion mutant than in wild-type cells under iron-limiting conditions. The transcripts of pfsR were enhanced by iron limitation and inactivation of the gene affected pronouncedly expression of fut genes (encoding a ferric iron transporter, feoB (encoding a ferrous iron transporter, bfr genes (encoding bacterioferritins, ho genes (encoding heme oxygenases, isiA (encoding a chlorophyll-binding protein, and furA (encoding a ferric uptake regulator. The iron quota in pfsR deletion mutant cells was higher than in wild-type cells both before and after exposure to iron limitation. Electrophoretic mobility shift assays showed that PfsR bound to its own promoter and thereby auto-regulated its own expression. These data suggest that PfsR is a critical regulator of iron homeostasis.

Molecular definition of multiple sites of antibody inhibition of malaria transmission-blocking vaccine antigen Pfs25.

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Scally, Stephen W; McLeod, Brandon; Bosch, Alexandre; Miura, Kazutoyo; Liang, Qi; Carroll, Sean; Reponen, Sini; Nguyen, Ngan; Giladi, Eldar; Rämisch, Sebastian; Yusibov, Vidadi; Bradley, Allan; Lemiale, Franck; Schief, William R; Emerling, Daniel; Kellam, Paul; King, C Richter; Julien, Jean-Philippe

2017-11-16

The Plasmodium falciparum Pfs25 protein (Pfs25) is a leading malaria transmission-blocking vaccine antigen. Pfs25 vaccination is intended to elicit antibodies that inhibit parasite development when ingested by Anopheles mosquitoes during blood meals. The Pfs25 three-dimensional structure has remained elusive, hampering a molecular understanding of its function and limiting immunogen design. We report six crystal structures of Pfs25 in complex with antibodies elicited by immunization via Pfs25 virus-like particles in human immunoglobulin loci transgenic mice. Our structural findings reveal the fine specificities associated with two distinct immunogenic sites on Pfs25. Importantly, one of these sites broadly overlaps with the epitope of the well-known 4B7 mouse antibody, which can be targeted simultaneously by antibodies that target a non-overlapping site to additively increase parasite inhibition. Our molecular characterization of inhibitory antibodies informs on the natural disposition of Pfs25 on the surface of ookinetes and provides the structural blueprints to design next-generation immunogens.

Skin rash in patients treated with neoadjuvant erlotinib (Tarceva in resectable non-small cell lung cancer: Predictor for tumor response and survival?

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Van Gool MH

2017-08-01

Full Text Available Background: Skin rash during treatment with epidermal growth factor receptor (EGFR-tyrosine kinase inhibitors (TKI has been reported to be predictive for response and survival in patients with advanced non-small cell lung cancer (NSCLC. The aim of this analysis was to evaluate whether skin rash during treatment (as a biomarker in a preoperative setting was related to response and survival. Methods: This study was designed as an open-label phase II trial (also known as M06NEL. Patients received preoperative erlotinib (Tarceva 150 mg once daily for 3 weeks. Skin toxicity during treatment was analysed in relation to metabolic and histopathological response, overall survival (OS and progression-free survival (PFS. Results: In total 59 patients (25 male, 34 female were eligible for analysis. In 39 patients (66% skin toxicity occurred. According to National Cancer Institute Common Toxicity Criteria (NCICTC, Grade 1 toxicity was seen in 15 patients (25%, Grade 2 in 19 patients (32% and Grade 3 in five patients (8%. None of the patients showed skin toxicity Grade 4 and 5. The median follow up was 74 months. Thirty-six patients (61% were alive at time of analysis. Twenty-seven patients (46% showed disease progression during follow up. Hazard ratios (HR indicated lower risk of death (HR = 0.66, 95%CI: 0.29 - 1.50 and progression (HR = 0.64, 0.30 - 1.36, although in this small group results were not significant. Skin rash did not adequately predict response. Conclusions: In this neoadjuvant setting with limited treatment time in patients with early stage NSCLC, skin rash was not associated with response and survival and cannot be used as an early biomarker.

The maximum standardized uptake value of 18 F-FDG PET scan to determine prognosis of hormone-receptor positive metastatic breast cancer

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Zhang Jian

2013-01-01

Full Text Available Abstract Background Whether PET scan maximum standard uptake value (SUVmax could differentiate luminal A from luminal B and help predict the survival of metastatic breast cancer (MBC patients with luminal subtype is still unknown and need to be investigated. Methods 305 MBC patients with luminal subtypes were screened with PET/CT. Eligible patients were prospectively followed up. Results In total, 134 patients were eligible for this study. SUVmax was significantly related to the number of metastatic sites and presence of visceral metastasis on univariate analysis. SUVmax could not effectively differentiate patients with luminal A from luminal B subtype. Although luminal subtype at diagnosis could predict the relapse-free interval, it could not predict progression-free survival (PFS or overall survival (OS after developing relapse. In contrast, SUVmax was predictive of both PFS and OS and this effect was maintained in multivariate COX regression model. Conclusions SUVmax of MBC did not correlate with molecular subtypes of primary tumor. While molecular subtype may be a valuable prognostic factor at primary diagnosis of breast cancer, the SUVmax, rather than molecular subtype, does have a potential to predict independently in multivariate analysis for the PFS and OS in patients with metastatic disease of luminal subtype.

Role of Adjuvant Radiation Therapy After Surgery for Abdominal Desmoplastic Small Round Cell Tumors

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Atallah, Vincent [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Honore, Charles [Department of Digestive Surgery, Gustave-Roussy Institute, Paris (France); Orbach, Daniel; Helfre, Sylvie [Department of Pediatric Oncology, Curie Institute, Paris (France); Ducassou, Anne [Department of Radiation Oncology, Universitary Cancer Institute, Toulouse (France); Thomas, Laurence [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Levitchi, Mihai-Barbu [Department of Radiation Oncology, Alexis-Vautrin Center, Nancy (France); Mervoyer, Augustin [Department of Radiation Oncology, Cancerologie de l' ouest Institute, Nantes (France); Naji, Salem [Department of Radiation Oncology, Paoli-Calmette Institute, Marseille (France); Dupin, Charles [Department of Radiation Oncology, Universitary Hospital, Bordeaux (France); Bosco-Levy, Pauline J. [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Philippe-Chomette, Pascale [Department of Pediatric Surgery, University Paris 7 Denis Diderot, Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, Paris (France); Kantor, Guy; Henriques de Figueiredo, Benedicte [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France); Sunyach, Marie-Pierre [Department of Radiation Oncology, Leon-Berard Center, Lyon (France); Sargos, Paul, E-mail: p.sargos@bordeaux.unicancer.fr [Department of Radiation Oncology, Bergonie Institute, Bordeaux (France)

2016-07-15

Purpose: To identify the prognostic role of adjuvant abdominal radiation therapy (RT) on oncologic outcomes as a part of multimodal treatment in the management of desmoplastic small round cell tumor (DSRCT) and to determine its impact according to the quality of surgical resection. Methods and Materials: All patients treated for primary abdominal DSRCT in 8 French centers from 1991 to 2014 were included. Patients were retrospectively staged into 3 groups: group A treated with adjuvant RT after cytoreductive surgery, group B without RT after cytoreductive surgery, and group C by exclusive chemotherapy. Peritoneal progression-free survival (PPFS), progression-free survival (PFS), and overall survival (OS) were evaluated. We also performed a direct comparison between groups A and B to evaluate RT after cytoreductive surgery. Radiation therapy was also evaluated according to completeness of surgery: complete cytoreductive surgery (CCS) or incomplete cytoreductive surgery (ICS). Results: Thirty-seven (35.9%), thirty-six (34.9%), and thirty (28.0%) patients were included in groups A, B, and C, respectively. Three-year OS was 61.2% (range, 41.0%-76.0%), 37.6% (22.0%-53.1%), and 17.3% (6.3%-32.8%) for groups A, B, and C, respectively. Overall survival, PPFS, and PFS differed significantly among the 3 groups (P<.001, P<.001, and P<.001, respectively). Overall survival and PPFS were higher in group A (RT group) compared with group B (no RT group) (P=.045 and P=.006, respectively). Three-year PPFS was 23.8% (10.3%-40.4%) for group A and 12.51% (4.0%-26.2%) for group B. After CCS, RT improved PPFS (P=.024), but differences in OS and PFS were not significant (P=.40 and P=.30, respectively). After ICS, RT improved OS (P=.044). A trend of PPFS and PFS increase was observed, but the difference was not statistically significant (P=.073 and P=.076). Conclusions: Adjuvant RT as part of multimodal treatment seems to confer oncologic benefits for patients treated for abdominal DSRCT

Long-term follow-up of patients receiving allogeneic stem cell transplant for chronic lymphocytic leukaemia: mixed T-cell chimerism is associated with high relapse risk and inferior survival.

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Thompson, Philip A; Stingo, Francesco; Keating, Michael J; Wierda, William G; O'Brien, Susan M; Estrov, Zeev; Ledesma, Celina; Rezvani, Katayoun; Qazilbash, Muzaffar; Shah, Nina; Parmar, Simrit; Popat, Uday; Anderlini, Paolo; Yago, Nieto; Ciurea, Stefan O; Kebriaei, Partow; Champlin, Richard; Shpall, Elizabeth J; Hosing, Chitra M

2017-05-01

There is limited information regarding the immunological predictors of post-allogeneic stem cell transplant (alloSCT) outcome in chronic lymphocytic leukaemia (CLL), such as mixed T-cell chimerism. We analysed 143 consecutive patients with relapsed/refractory CLL, transplanted between 2000 and 2012, to determine the prognostic relevance of mixed chimerism post-alloSCT and the ability of post-transplant immunomodulation to treat relapse. Mixed T-cell chimerism occurred in 50% of patients at 3 months and 43% at 6 months post-alloSCT; upon 3- and 6-month landmark analysis, this was associated with inferior progression-free survival (PFS) [Hazard ratio (HR) 1·93, P = 0·003 and HR 2·58, P CLL. © 2017 John Wiley & Sons Ltd.

Phase I/II trial of vorinostat (SAHA) and erlotinib for non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations after erlotinib progression.

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Reguart, Noemi; Rosell, Rafael; Cardenal, Felipe; Cardona, Andres F; Isla, Dolores; Palmero, Ramon; Moran, Teresa; Rolfo, Christian; Pallarès, M Cinta; Insa, Amelia; Carcereny, Enric; Majem, Margarita; De Castro, Javier; Queralt, Cristina; Molina, Miguel A; Taron, Miquel

2014-05-01

Vorinostat or suberoylanilide hydroxamic acid (SAHA) is a novel histone deacetylase inhibitor with demonstrated antiproliferative effects due to drug-induced accumulation of acetylated proteins, including the heat shock protein 90. We prospectively studied the activity of vorinostat plus erlotinib in EGFR-mutated NSCLC patients with progression to tyrosine kinase inhibitors. We conducted this prospective, non-randomized, multicenter, phase I/II trial to evaluate the maximum tolerated dose, toxicity profile and efficacy of erlotinib and vorinostat. Patients with advanced NSCLC harboring EGFR mutations and progressive disease after a minimum of 12 weeks on erlotinib were included. The maximum tolerated dose of vorinostat plus erlotinib was used as recommended dose for the phase II (RDP2) to assess the efficacy of the combination. The primary end point was progression-free-survival rate at 12 weeks (PFSR12w). Pre-treatment plasma samples were required to assess T790M resistant mutation. A total of 33 patients were enrolled in the phase I-II trial. The maximum tolerated dose was erlotinib 150 mg p.o., QD, and 400mg p.o., QD, on days 1-7 and 15-21 in a 28-day cycle. Among the 25 patients treated at the RDP2, the most common toxicities included anemia, fatigue and diarrhea. No responses were observed. PFSR12w was 28% (IC 95%: 18.0-37.2); median progression-free survival (PFS) was 8 weeks (IC 95%: 7.43-8.45) and overall survival (OS) 10.3 months (95% CI: 2.4-18.1). Full dose of continuous erlotinib with vorinostat 400mg p.o., QD on alternative weeks can be safely administered. Still, the combination has no meaningful activity in EGFR-mutated NSCLC patients after TKI progression. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Classification and Regression Tree Analysis of Clinical Patterns that Predict Survival in 127 Chinese Patients with Advanced Non-small Cell Lung Cancer Treated by Gefitinib Who Failed to Previous Chemotherapy

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Ziping WANG

2011-09-01

Full Text Available Background and objective It has been proven that gefitinib produces only 10%-20% tumor regression in heavily pretreated, unselected non-small cell lung cancer (NSCLC patients as the second- and third-line setting. Asian, female, nonsmokers and adenocarcinoma are favorable factors; however, it is difficult to find a patient satisfying all the above clinical characteristics. The aim of this study is to identify novel predicting factors, and to explore the interactions between clinical variables and their impact on the survival of Chinese patients with advanced NSCLC who were heavily treated with gefitinib in the second- or third-line setting. Methods The clinical and follow-up data of 127 advanced NSCLC patients referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from March 2005 to March 2010 were analyzed. Multivariate analysis of progression-free survival (PFS was performed using recursive partitioning, which is referred to as the classification and regression tree (CART analysis. Results The median PFS of 127 eligible consecutive advanced NSCLC patients was 8.0 months (95%CI: 5.8-10.2. CART was performed with an initial split on first-line chemotherapy outcomes and a second split on patients’ age. Three terminal subgroups were formed. The median PFS of the three subsets ranged from 1.0 month (95%CI: 0.8-1.2 for those with progressive disease outcome after the first-line chemotherapy subgroup, 10 months (95%CI: 7.0-13.0 in patients with a partial response or stable disease in first-line chemotherapy and age <70, and 22.0 months for patients obtaining a partial response or stable disease in first-line chemotherapy at age 70-81 (95%CI: 3.8-40.1. Conclusion Partial response, stable disease in first-line chemotherapy and age ≥ 70 are closely correlated with long-term survival treated by gefitinib as a second- or third-line setting in advanced NSCLC. CART can be used to identify previously unappreciated patient

Bevacizumab plus capecitabine in patients with progressive advanced well-differentiated neuroendocrine tumors of the gastro-intestinal (GI-NETs) tract (BETTER trial)--a phase II non-randomised trial.

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Mitry, Emmanuel; Walter, Thomas; Baudin, Eric; Kurtz, Jean-Emmanuel; Ruszniewski, Philippe; Dominguez-Tinajero, Sophie; Bengrine-Lefevre, Leïla; Cadiot, Guillaume; Dromain, Clarisse; Farace, Françoise; Rougier, Philippe; Ducreux, Michel

2014-12-01

Gastro-intestinal neuroendocrine tumours (GI-NETs) are chemotherapy-resistant tumours. Bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF), has shown promising results in several phase II trials of gastro-entero-pancreatic-NETs. We assessed bevacizumab combined with capecitabine, specifically in GI-NET patients. BEvacizumab in The Treament of neuroEndocrine tumoRs (BETTER) was a multicentre, open-label, non-randomised, two-group phase II trial. Here we present the group of patients with progressive, metastatic, well-differentiated GI-NETs. Patients Eastern Cooperative Oncology Group-performance status (ECOG-PS)⩽2, Ki-67 proliferation rate <15% and no prior systemic chemotherapy were treated with bevacizumab (7.5 mg/kg/q3w) and capecitabine (1000 mg/m2 twice daily, orally d1-14, resumed on d22) for 6-24 months. The primary end-point was progression-free survival (PFS); secondary end-points included overall survival (OS), response rate, safety and quality of life. Of the 49 patients included, 53% were men, median age was 60 years (41-82), primary tumour site was ileal in 82% patients and Ki-67 was <15% in 48 patients and not available for one patient. After a maximum of 24 month follow-up per patient, the median PFS by investigator assessment was 23.4 months [95% confidence interval (CI): 13.2; not reached] and the overall disease control rate was 88% (18% partial response, 70% stable disease). The 2-year survival rate was 85%. Median OS was not reached. The most frequent grade 3-4 adverse events were hypertension (31%), diarrhoea (14%) and hand-foot syndrome (10%). The combination of bevacizumab and capecitabine showed clinical activity and a manageable safety profile in the treatment of GI-NETs that warrant confirmation in a randomised phase III trial. Copyright © 2014 Elsevier Ltd. All rights reserved.

Prostate-Specific Antigen Persistence After Radical Prostatectomy as a Predictive Factor of Clinical Relapse-Free Survival and Overall Survival: 10-Year Data of the ARO 96-02 Trial

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Wiegel, Thomas, E-mail: thomas.wiegel@uniklinik-ulm.de [Department of Radiation Oncology, University Hospital Ulm (Germany); Bartkowiak, Detlef; Bottke, Dirk; Thamm, Reinhard [Department of Radiation Oncology, University Hospital Ulm (Germany); Hinke, Axel [WiSP, Research Institute Pharma GmbH, Langenfeld (Germany); Stöckle, Michael [Department of Urology, University Hospital Homburg/Saar (Germany); Rübe, Christian [Department of Radiation Oncology, University Hospital Homburg/Saar (Germany); Semjonow, Axel [Department of Urology, University Hospital Münster (Germany); Wirth, Manfred [Department of Urology, University Hospital Dresden (Germany); Störkel, Stephan; Golz, Reinhard [Department of Pathology, HELIOS Hospital Wuppertal (Germany); Engenhart-Cabillic, Rita [Department of Radiation Oncology, University Hospital Giessen-Marburg (Germany); Hofmann, Rainer [Department of Urology, University Hospital Giessen-Marburg (Germany); Feldmann, Horst-Jürgen [Department of Radiation Oncology, General Hospital Fulda (Germany); Kälble, Tilman [Department of Urology, General Hospital Fulda (Germany); Siegmann, Alessandra; Hinkelbein, Wolfgang [Department of Radiation Oncology, University Hospital Berlin (Germany); Steiner, Ursula; Miller, Kurt [Department of Urology, University Hospital Berlin (Germany)

2015-02-01

Objective: The ARO 96-02 trial primarily compared wait-and-see (WS, arm A) with adjuvant radiation therapy (ART, arm B) in prostate cancer patients who achieved an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP). Here, we report the outcome with up to 12 years of follow-up of patients who retained a post-RP detectable PSA and received salvage radiation therapy (SRT, arm C). Methods and Materials: For the study, 388 patients with pT3-4pN0 prostate cancer with positive or negative surgical margins were recruited. After RP, 307 men achieved an undetectable PSA (arms A + B). In 78 patients the PSA remained above thresholds (median 0.6, range 0.05-5.6 ng/mL). Of the latter, 74 consented to receive 66 Gy to the prostate bed, and SRT was applied at a median of 86 days after RP. Clinical relapse-free survival, metastasis-free survival, and overall survival were determined by the Kaplan-Meier method. Results: Patients with persisting PSA after RP had higher preoperative PSA values, higher tumor stages, higher Gleason scores, and more positive surgical margins than did patients in arms A + B. For the 74 patients, the 10-year clinical relapse-free survival rate was 63%. Forty-three men had hormone therapy; 12 experienced distant metastases; 23 patients died. Compared with men who did achieve an undetectable PSA, the arm-C patients fared significantly worse, with a 10-year metastasis-free survival of 67% versus 83% and overall survival of 68% versus 84%, respectively. In Cox regression analysis, Gleason score ≥8 (hazard ratio [HR] 2.8), pT ≥ 3c (HR 2.4), and extraprostatic extension ≥2 mm (HR 3.6) were unfavorable risk factors of progression. Conclusions: A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups

Overall survival and disease-free survival in endometrial cancer: prognostic factors in 276 patients

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Tejerizo-García A

2013-09-01

Full Text Available Álvaro Tejerizo-García,1 Jesús S Jiménez-López,1 José L Muñoz-González,1 Sara Bartolomé-Sotillos,1 Laura Marqueta-Marqués,1 Gregorio López-González,1 José F Pérez-Regadera Gómez21Service of Obstetrics and Gynecology, 2Radiation Oncology Service, Hospital Universitario 12 de Octubre, Madrid, SpainObjective: The aim of the study reported here was to assess the disease-free survival and overall survival of patients with endometrial cancer and to determine independent factors affecting the prognosis.Materials and methods: This was a retrospective study of a single-center clinical series of 276 patients (mean age 64 years with histologically confirmed cancer of the corpus uteri. The standard treatments were extrafascial total hysterectomy and bilateral salpingo-oophorectomy with selective pelvic/para-aortic node dissection, according to risk for recurrence. Actuarial overall survival and disease-free survival were estimated according to the Kaplan–Meier method. Univariate and multivariate Cox proportional hazards analyses were used to assess the prognostic significance of the different variables.Results: The estimated median follow-up, determined using the inverse Kaplan–Meier method, was 45 months (95% confidence interval [CI] 41.2–48.8 for disease-free survival and 46 months (95% CI 43.0–49.0 for overall survival. The statistically significant variables affecting disease-free survival and overall survival were age, serous-papillary and clear-cell histological types, outer-half myometrial invasion, advanced International Federation of Gynecology and Obstetrics (FIGO stage, tumor grades G2 and G3, incomplete surgical resection, positive lymph nodes, lymphovascular space invasion, tumor remnants of >1 cm after surgery, and high-risk group. In the multivariate Cox regression model, predictors of tumor recurrence included advanced FIGO stage (hazard ratio [HR] 4.90, 95% CI 2.57–9.36, P < 0.001 and tumor grades G2 (HR 4.79, 95

Exponential Decay Nonlinear Regression Analysis of Patient Survival Curves: Preliminary Assessment in Non-Small Cell Lung Cancer

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Stewart, David J.; Behrens, Carmen; Roth, Jack; Wistuba, Ignacio I.

2010-01-01

Background For processes that follow first order kinetics, exponential decay nonlinear regression analysis (EDNRA) may delineate curve characteristics and suggest processes affecting curve shape. We conducted a preliminary feasibility assessment of EDNRA of patient survival curves. Methods EDNRA was performed on Kaplan-Meier overall survival (OS) and time-to-relapse (TTR) curves for 323 patients with resected NSCLC and on OS and progression-free survival (PFS) curves from selected publications. Results and Conclusions In our resected patients, TTR curves were triphasic with a “cured” fraction of 60.7% (half-life [t1/2] >100,000 months), a rapidly-relapsing group (7.4%, t1/2=5.9 months) and a slowly-relapsing group (31.9%, t1/2=23.6 months). OS was uniphasic (t1/2=74.3 months), suggesting an impact of co-morbidities; hence, tumor molecular characteristics would more likely predict TTR than OS. Of 172 published curves analyzed, 72 (42%) were uniphasic, 92 (53%) were biphasic, 8 (5%) were triphasic. With first-line chemotherapy in advanced NSCLC, 87.5% of curves from 2-3 drug regimens were uniphasic vs only 20% of those with best supportive care or 1 drug (p<0.001). 54% of curves from 2-3 drug regimens had convex rapid-decay phases vs 0% with fewer agents (p<0.001). Curve convexities suggest that discontinuing chemotherapy after 3-6 cycles “synchronizes” patient progression and death. With postoperative adjuvant chemotherapy, the PFS rapid-decay phase accounted for a smaller proportion of the population than in controls (p=0.02) with no significant difference in rapid-decay t1/2, suggesting adjuvant chemotherapy may move a subpopulation of patients with sensitive tumors from the relapsing group to the cured group, with minimal impact on time to relapse for a larger group of patients with resistant tumors. In untreated patients, the proportion of patients in the rapid-decay phase increased (p=0.04) while rapid-decay t1/2 decreased (p=0.0004) with increasing

Fludarabine plus alemtuzumab (FA) front-line treatment in young patients with chronic lymphocytic leukemia (CLL) and an adverse biologic profile.

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Mauro, Francesca R; Molica, Stefano; Laurenti, Luca; Cortelezzi, Agostino; Carella, Angelo M; Zaja, Francesco; Chiarenza, Annalisa; Angrilli, Francesco; Nobile, Francesco; Marasca, Roberto; Musolino, Caterina; Brugiatelli, Maura; Piciocchi, Alfonso; Vignetti, Marco; Fazi, Paola; Gentile, Giuseppe; De Propris, Maria S; Della Starza, Irene; Marinelli, Marilisa; Chiaretti, Sabina; Del Giudice, Ilaria; Nanni, Mauro; Albano, Francesco; Cuneo, Antonio; Guarini, Anna; Foà, Robin

2014-02-01

In 45, ≤ 60 years old patients with CLL and an adverse biologic profile, a front-line treatment with Fludarabine and Campath (Alemtuzumab(®)) was given. The overall response rate was 75.5%, the complete response rate (CR) 24.4% with the lowest CR rates, 16.7% and 8.3%, in 11q and 17p deleted cases. The 3-year progression-free survival (PFS) and overall survival were 42.5% and 79.9%, respectively. PFS was significantly influenced by CLL duration, beta2-microglobulin, and improved by post-remissional stem cell transplantation. Front-line fludarabine and alemtuzumab showed a manageable safety profile and evidence of a benefit in a small series of CLL patients with adverse biologic features. Copyright © 2013 Elsevier Ltd. All rights reserved.

Adding bevacizumab to single agent chemotherapy for the treatment of platinum-resistant recurrent ovarian cancer: A cost effectiveness analysis of the AURELIA trial.

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Wysham, Weiya Z; Schaffer, Elisabeth M; Coles, Theresa; Roque, Dario R; Wheeler, Stephanie B; Kim, Kenneth H

2017-05-01

AURELIA, a randomized phase III trial of adding bevacizumab (B) to single agent chemotherapy (CT) for the treatment of platinum-resistant recurrent ovarian cancer, demonstrated improved progression free survival (PFS) in the B+CT arm compared to CT alone. We aimed to evaluate the cost effectiveness of adding B to CT in the treatment of platinum-resistant recurrent ovarian cancer. A decision tree model was constructed to evaluate the cost effectiveness of adding bevacizumab (B) to single agent chemotherapy (CT) based on the arms of the AURELIA trial. Costs, quality-adjusted life years (QALYs), and progression free survival (PFS) were modeled over fifteen months. Model inputs were extracted from published literature and public sources. Incremental cost effectiveness ratios (ICERs) per QALY gained and ICERs per progression free life year saved (PF-LYS) were calculated. One-way sensitivity analyses were performed to evaluate the robustness of results. The ICER associated with B+CT is $410,455 per QALY gained and $217,080 per PF-LYS. At a willingness to pay (WTP) threshold of $50,000/QALY, adding B to single agent CT is not cost effective for this patient population. Even at a WTP threshold of $100,000/QALY, B+CT is not cost effective. These findings are robust to sensitivity analyses. Despite gains in QALY and PFS, the addition of B to single agent CT for treatment of platinum-resistant recurrent ovarian cancer is not cost effective. Benefits, risks, and costs associated with treatment should be taken into consideration when prescribing chemotherapy for this patient population. Copyright © 2017 Elsevier Inc. All rights reserved.

Clinical value of circulating endothelial cell levels in metastatic colorectal cancer patients treated with first-line chemotherapy and bevacizumab.

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Malka, D; Boige, V; Jacques, N; Vimond, N; Adenis, A; Boucher, E; Pierga, J Y; Conroy, T; Chauffert, B; François, E; Guichard, P; Galais, M P; Cvitkovic, F; Ducreux, M; Farace, F

2012-04-01

We investigated whether circulating endothelial cells (CECs) predict clinical outcome of first-line chemotherapy and bevacizumab in metastatic colorectal cancer (mCRC) patients. In a substudy of the randomized phase II FNCLCC ACCORD 13/0503 trial, CECs (CD45- CD31+ CD146+ 7-amino-actinomycin- cells) were enumerated in 99 patients by four-color flow cytometry at baseline and after one cycle of treatment. We correlated CEC levels with objective response rate (ORR), 6-month progression-free survival (PFS) rate (primary end point of the trial), PFS, and overall survival (OS). Multivariate analyses of potential prognostic factors, including CEC counts and Köhne score, were carried out. By multivariate analysis, high baseline CEC levels were the only independent prognostic factor for 6-month PFS rate (P < 0.01) and were independently associated with worse PFS (P = 0.02). High CEC levels after one cycle were the only independent prognostic factor for ORR (P = 0.03). High CEC levels at both time points independently predicted worse ORR (P = 0.025), 6-month PFS rate (P = 0.007), and PFS (P = 0.02). Köhne score was the only variable associated with OS. CEC levels at baseline and after one treatment cycle may independently predict ORR and PFS in mCRC patients starting first-line bevacizumab and chemotherapy.

Randomized phase II study of vandetanib alone or with paclitaxel and carboplatin as first-line treatment for advanced non-small-cell lung cancer.

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Heymach, John V; Paz-Ares, Luis; De Braud, Filippo; Sebastian, Martin; Stewart, David J; Eberhardt, Wilfried E E; Ranade, Anantbhushan A; Cohen, Graham; Trigo, Jose Manuel; Sandler, Alan B; Bonomi, Philip D; Herbst, Roy S; Krebs, Annetta D; Vasselli, James; Johnson, Bruce E

2008-11-20

Vandetanib is a once-daily, oral inhibitor of vascular endothelial growth factor receptor and epidermal growth factor receptor signaling. The antitumor activity of vandetanib monotherapy or vandetanib with paclitaxel and carboplatin (VPC) was compared with paclitaxel and carboplatin (PC) in previously untreated patients with non-small-cell lung cancer (NSCLC). All NSCLC histologies and previously treated CNS metastases were permitted in this partially blinded, placebo-controlled, randomized phase II study. Patients were randomly assigned 2:1:1 to receive vandetanib, VPC, or PC. Progression-free survival (PFS) was the primary end point, and the study was powered to detect a reduced risk of progression with VPC versus PC (hazard ratio = 0.70; one-sided P 1.33 v PC). Overall survival was not significantly different between patients receiving VPC or PC. Rash, diarrhea, and hypertension were common adverse events; no pulmonary or CNS hemorrhage events required intervention. VPC could be safely administered to patients with NSCLC, including those with squamous cell histology and treated brain metastases. Compared with the PC control arm, patients receiving VPC had longer PFS, meeting the prespecified study end point, whereas those receiving vandetanib monotherapy had shorter PFS.

Economic outcomes of maintenance gefitinib for locally advanced/metastatic non-small-cell lung cancer with unknown EGFR mutations: a semi-Markov model analysis.

Directory of Open Access Journals (Sweden)

Xiaohui Zeng

Full Text Available BACKGROUND: Maintenance gefitinib significantly prolonged progression-free survival (PFS compared with placebo in patients from eastern Asian with locally advanced/metastatic non-small-cell lung cancer (NSCLC after four chemotherapeutic cycles (21 days per cycle of first-line platinum-based combination chemotherapy without disease progression. The objective of the current study was to evaluate the cost-effectiveness of maintenance gefitinib therapy after four chemotherapeutic cycle's stand first-line platinum-based chemotherapy for patients with locally advanced or metastatic NSCLC with unknown EGFR mutations, from a Chinese health care system perspective. METHODS AND FINDINGS: A semi-Markov model was designed to evaluate cost-effectiveness of the maintenance gefitinib treatment. Two-parametric Weibull and Log-logistic distribution were fitted to PFS and overall survival curves independently. One-way and probabilistic sensitivity analyses were conducted to assess the stability of the model designed. The model base-case analysis suggested that maintenance gefitinib would increase benefits in a 1, 3, 6 or 10-year time horizon, with incremental $184,829, $19,214, $19,328, and $21,308 per quality-adjusted life-year (QALY gained, respectively. The most sensitive influential variable in the cost-effectiveness analysis was utility of PFS plus rash, followed by utility of PFS plus diarrhoea, utility of progressed disease, price of gefitinib, cost of follow-up treatment in progressed survival state, and utility of PFS on oral therapy. The price of gefitinib is the most significant parameter that could reduce the incremental cost per QALY. Probabilistic sensitivity analysis indicated that the cost-effective probability of maintenance gefitinib was zero under the willingness-to-pay (WTP threshold of $16,349 (3 × per-capita gross domestic product of China. The sensitivity analyses all suggested that the model was robust. CONCLUSIONS: Maintenance gefitinib

Salvage bortezomib-dexamethasone and high-dose melphalan (HDM) and autologous stem cell support (ASCT) in myeloma patients at first relapse after HDM with ASCT. A phase-2 trial

DEFF Research Database (Denmark)

Gimsing, P; Hjertner, Ø; Abildgaard, N

2015-01-01

, there was no significant difference of PFS and TNT after HDM (II) compared with after the initial HDM(I), and thus patients were their own controls (PFS (I: 20.1 vs II: 19.3 months (P=0.8)) or TNT (I: 24.4 vs II: 20.7 months (P=0.8)). No significant differences in the response rates after salvage ASCT compared......Until recently, only retrospective studies had been published on salvage high-dose melphalan (HDM) with autologous stem cell 'transplantation' (ASCT). In a prospective, nonrandomized phase-2 study, we treated 53 bortezomib-naïve patients with bortezomib-dexamethasone as induction and bortezomib...... included in the conditioning regimen along with the HDM. Median progression-free survival (PFS), time to next treatment (TNT) and overall survival (OS) after start of reinduction therapy were 21.6, 22.8 and 46.6 months, respectively. For 49 patients who completed salvage bortezomib-HDM(II) with ASCT...

Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer: A retrospective study.

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Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

2018-04-01

This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population.A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study.The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study.This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population.

Icotinib and whole-brain radiotherapy for the treatment in patients with brain metastases from EGFR-mutant nonsmall cell lung cancer

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Jiang, Ai-Ying; Zhang, Jing; Luo, Hai-Long; Gao, Feng; Lv, Yu-Feng

2018-01-01

Abstract This study aimed to explore the effect and toxicity of icotinib and whole-brain radiotherapy (IWBRT) for the treatment of brain metastases from nonsmall cell lung cancer (BMNSCLC) with epidermal growth factor receptor (EGFR)-mutant among Chinese Han population. A total of 55 patients with EGFR-mutant BMNSCLC were included. They received orally icotinib (125 mg/tablet, 125 mg each time, 3 times daily) until disease progression. In addition, they also underwent whole-brain radiotherapy (3-Gy fractions once daily, 5 days weekly for a total dose of 30 Gy) in an attempt to extend their survival time. The outcomes consisted of complete response (CR), partial response (PR), stable disease (SD), progress disease (PD), overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). In addition, toxicity was also recorded in this study. The CR, PR, SD, PD, ORR, PFS, and OS were 38.2%, 52.8%, 5.4%, 3.6%, 90.1%, 12.5%, and 48.0% months, respectively. In addition, mild toxicity was observed in this study. This study demonstrated that IWBRT is efficacious with acceptable toxicity for patients with EGFR-mutant BMNSCLC among Chinese Han population. PMID:29642161

Prognostic Value of CD109+ Circulating Endothelial Cells in Recurrent Glioblastomas Treated with Bevacizumab and Irinotecan

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Cuppini, Lucia; Calleri, Angelica; Bruzzone, Maria Grazia; Prodi, Elena; Anghileri, Elena; Pellegatta, Serena; Mancuso, Patrizia; Porrati, Paola; Di Stefano, Anna Luisa; Ceroni, Mauro; Bertolini, Francesco; Finocchiaro, Gaetano; Eoli, Marica

2013-01-01

Background Recent data suggest that circulating endothelial and progenitor cells (CECs and CEPs, respectively) may have predictive potential in cancer patients treated with bevacizumab, the antibody recognizing vascular endothelial growth factor (VEGF). Here we report on CECs and CEPs investigated in 68 patients affected by recurrent glioblastoma (rGBM) treated with bevacizumab and irinotecan and two Independent Datasets of rGBM patients respectively treated with bevacizumab alone (n=32, independent dataset A: IDA) and classical antiblastic chemotherapy (n=14, independent dataset B: IDB). Methods rGBM patients with KPS ≥50 were treated until progression, as defined by MRI with RANO criteria. CECs expressing CD109, a marker of tumor endothelial cells, as well as other CEC and CEP subtypes, were investigated by six-color flow cytometry. Results A baseline count of CD109+ CEC higher than 41.1/ml (1st quartile) was associated with increased progression free survival (PFS; 20 versus 9 weeks, P=0.008) and overall survival (OS; 32 versus 23 weeks, P=0.03). Longer PFS (25 versus 8 weeks, P=0.02) and OS (27 versus 17 weeks, P=0.03) were also confirmed in IDA with CD109+ CECs higher than 41.1/ml but not in IDB. Patients treated with bevacizumab with or without irinotecan that were free from MRI progression after two months of treatment had significant decrease of CD109+ CECs: median PFS was 19 weeks; median OS 29 weeks. The presence of two non-contiguous lesions (distant disease) at baseline was an independent predictor of shorter PFS and OS (P<0.001). Conclusions Data encourage further studies on the predictive potential of CD109+ CECs in GBM patients treated with bevacizumab. PMID:24069296

Dust observations by PFS on Mars Express

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Zasova, L. V.; Formisano, V.; Moroz, V. I.; Grassi, D.; Ignatiev, N. I.; Blecka, M. I.; Maturilli, A.; Palomba, E.; Piccioni, G.; Pfs Team

Dust is always present in the Martian atmosphere with opacity, which changes from values below 0.1 (at 9 μ m) up to several units during the dust storms. From the thermal IR (LW channel of PFS) the dust opacity is retrieved in a self consistent way together with the temperature profile from the same spectrum A preliminary investigation along the orbit, which comes through Hellas, shows that the value of dust opacity anticorrelates with surface altitude. From -70 to +25 of latitude the vertical dust distribution follows the exponential low with the scale of 12 km, which corresponds to the gaseous scale height near noon and indicates for well mixed condition. The dust opacity, corresponding to the zero surface altitude, is found of 0.25+-0.05. More detailed investigations of all available data will be presented, including analysis of both short- and long- wavelength spectra of PFS.

Positron Emission Tomography/Computed Tomography Findings During Therapy Predict Outcome in Patients With Diffuse Large B-Cell Lymphoma Treated With Chemotherapy Alone but Not in Those Who Receive Consolidation Radiation

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Dabaja, Bouthaina S., E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hess, Kenneth [Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shihadeh, Ferial [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Podoloff, Donald A. [Department of Nuclear Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Medeiros, L. Jeffrey [Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Mawlawi, Osama [Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Arzu, Isidora [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Oki, Yasuhiro; Hagemeister, Fredrick B.; Fayad, Luis E. [Department of Lymphoma/Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Reed, Valerie K.; Kedir, Aziza; Wogan, Christine F. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez, Alma [Office of the Executive Vice President and Physician-in-Chief, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2014-06-01

Purpose: To assess the value of mid-therapy positron emission tomography (PET) findings for predicting survival and disease progression in patients with diffuse large B-cell lymphoma, considering type of therapy (chemotherapy with or without radiation therapy). Methods and Materials: We retrospectively evaluated 294 patients with histologically confirmed diffuse large B-cell lymphoma with respect to age, sex, disease stage, International Prognostic Index score, mid-therapy PET findings (positive or negative), and disease status after therapy and at last follow-up. Overall survival (OS) and progression-free survival (PFS) were compared according to mid-therapy PET findings. Results: Of the 294 patients, 163 (55%) were male, 144 (49%) were age >61 years, 110 (37%) had stage I or II disease, 219 (74%) had International Prognostic Index score ≤2, 216 (73%) received ≥6 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone, and 88 (30%) received consolidation radiation therapy. Five-year PFS and OS rates were associated with mid-therapy PET status: PFS was 78% for those with PET-negative (PET−) disease versus 63% for PET-positive (PET+) disease (P=.024), and OS was 82% for PET− versus 62% for PET+ (P<.002). These associations held true for patients who received chemotherapy only (PFS 71% for PET− vs 52% PET+ [P=.012], OS 78% for PET− and 51% for PET+ [P=.0055]) but not for those who received consolidation radiation therapy (PFS 84% PET− vs 81% PET+ [P=.88]; OS 90% PET− vs 81% PET+ [P=.39]). Conclusion: Mid-therapy PET can predict patient outcome, but the use of consolidation radiation therapy may negate the significance of mid-therapy findings.

A Retrospective Analysis of Precision Medicine Outcomes in Patients With Advanced Cancer Reveals Improved Progression-Free Survival Without Increased Health Care Costs.

Science.gov (United States)

Haslem, Derrick S; Van Norman, S Burke; Fulde, Gail; Knighton, Andrew J; Belnap, Tom; Butler, Allison M; Rhagunath, Sharanya; Newman, David; Gilbert, Heather; Tudor, Brian P; Lin, Karen; Stone, Gary R; Loughmiller, David L; Mishra, Pravin J; Srivastava, Rajendu; Ford, James M; Nadauld, Lincoln D

2017-02-01

The advent of genomic diagnostic technologies such as next-generation sequencing has recently enabled the use of genomic information to guide targeted treatment in patients with cancer, an approach known as precision medicine. However, clinical outcomes, including survival and the cost of health care associated with precision cancer medicine, have been challenging to measure and remain largely unreported. We conducted a matched cohort study of 72 patients with metastatic cancer of diverse subtypes in the setting of a large, integrated health care delivery system. We analyzed the outcomes of 36 patients who received genomic testing and targeted therapy (precision cancer medicine) between July 1, 2013, and January 31, 2015, compared with 36 historical control patients who received standard chemotherapy (n = 29) or best supportive care (n = 7). The average progression-free survival was 22.9 weeks for the precision medicine group and 12.0 weeks for the control group ( P = .002) with a hazard ratio of 0.47 (95% CI, 0.29 to 0.75) when matching on age, sex, histologic diagnosis, and previous lines of treatment. In a subset analysis of patients who received all care within the Intermountain Healthcare system (n = 44), per patient charges per week were $4,665 in the precision treatment group and $5,000 in the control group ( P = .126). These findings suggest that precision cancer medicine may improve survival for patients with refractory cancer without increasing health care costs. Although the results of this study warrant further validation, this precision medicine approach may be a viable option for patients with advanced cancer.

The protein kinase C (PKC) inhibitors combined with chemotherapy in the treatment of advanced non-small cell lung cancer: meta-analysis of randomized controlled trials.

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Zhang, L L; Cao, F F; Wang, Y; Meng, F L; Zhang, Y; Zhong, D S; Zhou, Q H

2015-05-01

The application of newer signaling pathway-targeted agents has become an important addition to chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the efficacy and toxicities of PKC inhibitors combined with chemotherapy versus chemotherapy alone for patients with advanced NSCLC systematically. Literature retrieval, trials selection and assessment, data collection, and statistic analysis were performed according to the Cochrane Handbook 5.1.0. The outcome measures were tumor response rate, disease control rate, progression-free survival (PFS), overall survival (OS), and adverse effects. Five randomized controlled trials, comprising totally 1,005 patients, were included in this study. Meta-analysis showed significantly decreased response rate (RR 0.79; 95 % CI 0.64-0.99) and disease control rate (RR 0.90; 95 % CI 0.82-0.99) in PKC inhibitors-chemotherapy groups versus chemotherapy groups. There was no significant difference between the two treatment groups regarding progression-free survival (PFS, HR 1.05; 95 % CI 0.91-1.22) and overall survival (OS, HR 1.00; 95 % CI 0.86-1.16). The risk of grade 3/4 neutropenia, leucopenia, and thrombosis/embolism increased significantly in PKC inhibitors combination groups as compared with chemotherapy alone groups. The use of PKC inhibitors in addition to chemotherapy was not a valid alternative for patients with advanced NSCLC.

The clinical use of neutrophil-to-lymphocyte ratio in bladder cancer patients: a systematic review and meta-analysis.

Science.gov (United States)

Tang, Xingxing; Du, Peng; Yang, Yong

2017-10-01

The aim of this study was to evaluate the evidence regarding the neutrophil-to-lymphocyte ratio (NLR) as a factor predictive of survival in bladder cancer patients. A search of PubMed and Embase for relevant studies between January 1, 1966 and November 10, 2016 was performed with the terms [NLR OR (neutrophil lymphocyte ratio)] AND [(bladder cancer) OR BCa OR NMIBC OR MIBC]. Inclusion required studies published in English containing bladder cancer patients and evaluating NLR as a predictive factor. Endpoints of NLR and survival data were extracted for pooled analysis. The pooled results showed that an elevated NLR was a predictor for poor overall survival (OS) [hazard ratio (HR) = 1.19, 95% confidence interval (CI) 1.07-1.31], cancer-specific survival (CSS) (HR = 1.40, 95% CI 1.17-1.69), recurrence-free survival (RFS) (HR = 1.58, 95% CI 1.24-2.03) and progression-free survival (PFS) (HR = 1.33, 95% CI 1.19-1.49) in patients with bladder cancer. Heterogeneity between studies was observed for OS, CSS and RFS, but not for PFS. Publication bias was detected for all these outcomes. Our results showed that elevated NLR might be valuable as a predictive factor of survival in bladder cancer patients.

Progress of PD-1/PD-L1 Inhibitors in Non-small Cell Lung Cancer

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Zhansheng JIANG

2017-02-01

Full Text Available Pembrolizumab, an inhibitor target programmed death 1 (PD-1, was approved into the first line therapy in advanced non-small cell lung cancer (NSCLC. It was a milestone that immune checkpoints drugs have played an important role in the treatment system of NSCLC. The results of clinical trials revealed the superiority of PD-1/programmed death ligand 1 (PD-L1 inhibitors compared with chemotherapy in first-line, second-line and multidrug resistance phase therapy. Objective response rate (ORR was up to 80% with pembrolizumab plus chemotherapy, and progression-free survival (PFS with single pembrolizumab in first line was nearly 1 year (10.3 months, the hazard ratio for death fell by 40%. Overall survival (OS was more or less 1 year with single drug pembrolizumab, nivolumab and atezolizumab for second line therapy. PD-L1 expression was a predictor of PD-1/PD-L1 inhibitors. The positive rate of PD-L1 (more than 1% in advanced NSCLC was about 60% with little difference between the tissue types. However, there was no gold standard test of PD-L1 expression.

Complete androgen blockade safely allows for delay of cytotoxic chemotherapy in castration refractory prostate cancer

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Rafael A. Kaliks

2010-06-01

Full Text Available PURPOSE: Complete androgen blockade (CAB does not prolong overall survival (OS in patients with castration refractory prostate cancer (CRPC. Although there is variable clinical benefit with second-line hormone manipulation, we do not know which patients might benefit the most. OBJECTIVES: To identify clinical predictors of benefit of complete androgen blockade. MATERIALS AND METHODS: We reviewed the records for 54 patients who received treatment with CAB in the setting of disease progression despite castration. We evaluated progression-free survival (PFS and OS according to PSA at diagnosis, Gleason scores, age, testosterone level, and duration of prior disease control during castration in first line treatment. RESULTS: Among 54 patients who received CAB, the median PFS was 9 months (CI 4.3-13.7 and OS was 36 months (CI 24-48. We did not find an effect of PSA at diagnosis (p = 0.32, Gleason score (p = 0.91, age (p = 0.69 or disease control during castration (p = 0.87 on PFS or OS. Thirty-four patients subsequently received chemotherapy, with a mean OS of 21 months (CI 16.4-25.5, median not reached. CONCLUSION: Age, Gleason score, PSA at diagnosis and length of disease control with castration did not affect PFS or OS. In the absence of predictors of benefit, CAB should still be considered in CRPC.

Impact of induction treatment before autologous stem cell transplantation on long-term outcome in patients with newly diagnosed multiple myeloma.

Science.gov (United States)

Gassiot, Susanna; Motlló, Cristina; Llombart, Inuska; Morgades, Mireia; González, Yolanda; Garcia-Caro, Montse; Ribera, Josep-Maria; Oriol, Albert

2017-06-01

Clinical trials for patients with multiple myeloma (MM) using novel agent (NA)-based regimens before autologous stem cell transplantation (SCT) have shown improvement in response rates and progression-free survival (PFS); however they have failed to identify a significant overall survival (OS) benefit. The aim of this study was to analyze the potential impact of initial induction on the feasibility and outcome of subsequent treatment lines in a real clinical practice setting. Patients with consecutive MM <70 years of age diagnosed between 1999 and 2009 were prospectively registered and classified as having received conventional chemotherapy induction regimens with new agents available at relapse (CC cohort, 89 patients) or as treated with NAs upfront (NA cohort, 65 patients). Patients in the NA cohort demonstrated a superior median PFS (2.8 years vs 1.6 years, P=.03) and also a median PFS from diagnosis to second progression (5.2 years vs 2.7 years, P=.003). After a median follow-up of 7 years, clear differences in OS were observed (7.97 years in NA cohort compared to 3.35 years in CC cohort, P<.001). New agent-based first-line induction treatments provide benefits in both PFS and beyond that point, contributing to a significant improvement in OS. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

mTOR-inhibitor treatment of metastatic renal cell carcinoma: contribution of Choi and modified Choi criteria assessed in 2D or 3D to evaluate tumor response

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Lamuraglia, M. [Laboratoire d' Imagerie Biomedicale, Sorbonne Universites, UPMC Univ Paris 06, INSERM, CNRS, Paris (France); Raslan, S.; Penna, R.R.; Wagner, M. [Groupe Hospitalier Pitie-Salpetriere, APHP UPMC, Service de Radiologie Polyvalente et Oncologique, Paris Cedex 13 (France); Elaidi, R.; Oudard, S. [APHP, Oncology Unit, Georges-Pompidou Hospital, Paris (France); Escudier, B. [Gustave-Roussy Institute, Medical Oncology Department, Villejuif (France); Slimane, K. [Novartis Pharma, Rueil-Malmaison (France); Lucidarme, O. [Groupe Hospitalier Pitie-Salpetriere, APHP UPMC, Service de Radiologie Polyvalente et Oncologique, Paris Cedex 13 (France); Laboratoire d' Imagerie Biomedicale, Sorbonne Universites, UPMC Univ Paris 06, INSERM, CNRS, Paris (France)

2016-01-15

To determine whether 2D or 3D Choi and modified Choi (mChoi) criteria could assess the efficacy of everolimus against metastatic renal cell carcinoma (mRCC). RECIST-1.1, Choi, and mChoi criteria were applied retrospectively to analyse baseline and 2-month contrast-enhanced computed tomography (CECT) images in 48 patients with mRCC enrolled in the everolimus arm of the French randomized double-blind multicentre phase III trial comparing everolimus versus placebo (RECORD-1). The primary endpoint was centrally reviewed progression-free survival (PFS) calculated from the initial RECORD-1 analysis. Mean attenuation was determined for 2D target lesion regions of interest drawn on CECT sections whose largest diameters had been measured, and for the 3D whole target lesion. The median PFS was 5.5 months. The median PFS for everolimus responders defined using 3D mChoi criteria was significantly longer than for non-responders (7.6 versus 5.4 months, respectively), corresponding to a hazard ratio for progression of 0.45 (95 % CI: 0.22-0.92), with respective 1-year survival rates of 31 % and 9 %. No other 2D or 3D imaging criteria at 2 months identified patients who would benefit from everolimus. At 2 months, only 3D mChoi criteria were able to identify mRCC patients with a PFS benefit from everolimus. (orig.)

Antibody responses to two new Lactococcus lactis-produced recombinant Pfs48/45 and Pfs230 proteins increase with age in malaria patients living in the Central Region of Ghana

DEFF Research Database (Denmark)

Acquah, Festus K.; Obboh, Evans K.; Asare, Kwame

2017-01-01

difficult to produce recombinantly in the absence of a fusion partner. Methods Regions of Pfs48/45 and Pfs230 known to contain transmission blocking epitopes, 6C and C0, respectively, were produced in a Lactococcus lactis expression system and used in enzyme linked immunosorbent assays to determine...

{sup 18}F-FDG PET/CT predicts survival after {sup 90}Y transarterial radioembolization in unresectable hepatocellular carcinoma

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Jreige, Mario; Mitsakis, Periklis; Gucht, Axel van der; Pomoni, Anastasia; Silva-Monteiro, Marina; Boubaker, Ariane; Nicod-Lalonde, Marie; Prior, John O.; Schaefer, Niklaus [Lausanne University Hospital, Department of Nuclear Medicine and Molecular Imaging, Lausanne (Switzerland); Gnesin, Silvano [Lausanne University Hospital, Institute of Radiation Physics, Lausanne (Switzerland); Duran, Rafael; Denys, Alban [Lausanne University Hospital, Department of Radiodiagnostic and Interventional Radiology, Lausanne (Switzerland)

2017-07-15

To compare the value of pretreatment functional and morphological imaging parameters for predicting survival in patients undergoing transarterial radioembolization using yttrium-90 ({sup 90}Y-TARE) for unresectable hepatocellular carcinoma (uHCC). We analysed data from 48 patients in our prospective database undergoing {sup 90}Y-TARE treatment for uHCC (31 resin, 17 glass). All patients underwent {sup 18}F-FDG PET/CT and morphological imaging (CT and MRI scans) as part of a pretherapeutic work-up. Patients did not receive any treatment between these imaging procedures and {sup 90}Y-TARE. Kaplan-Meier estimates of progression-free survival (PFS) and overall survival (OS) were used to assess the prognostic value of {sup 18}F-FDG PET/CT metabolic parameters, including SUV{sub max}, tumour-to-liver (T/L) uptake ratio and SUV{sub mean} of healthy liver, and morphological data, including number and size of lesions, portal-venous infiltration (PVI). Relevant prognostic factors for HCC including Child-Pugh class, Barcelona Clinic Liver Cancer (BCLC) stage, tumour size, PVI and serum AFP level were compared with metabolic parameters in univariate and multivariate analyses. The median follow-up in living patients was 16.2 months (range 11.4-50.1 months). Relapse occurred in 34 patients (70.8%) at a median of 7.4 months (range 1.4-27.9 months) after {sup 90}Y-TARE, and relapse occurred in 24 of 34 patients (70.8%) who died from their disease at a median of 8.1 months (range 2.2-35.2 months). Significant prognostic markers for PFS were the mean and median lesion SUV{sub max} (both P = 0.01; median PFS 10.2 vs. 7.4 months), and significant prognostic markers for OS were the first quarter (Q1) cut-off values for lesion SUV{sub max} and T/L uptake ratio (both P = 0.02; median OS 30.9 vs. 9 months). The multivariate analysis confirmed that lesion SUV{sub max} and T/L uptake ratio were independent negative predictors of PFS (hazard ratio, HR, 2.7, 95% CI 1.2-6.1, P = 0.02, for mean

Quality of life is significantly associated with survival in women with advanced epithelial ovarian cancer: An ancillary data analysis of the NRG Oncology/Gynecologic Oncology Group (GOG-0218) study.

Science.gov (United States)

Phippen, N T; Secord, A A; Wolf, S; Samsa, G; Davidson, B; Abernethy, A P; Cella, D; Havrilesky, L J; Burger, R A; Monk, B J; Leath, C A

2017-10-01

Evaluate association between baseline quality of life (QOL) and changes in QOL measured by FACT-O TOI with progression-free disease (PFS) and overall survival (OS) in advanced epithelial ovarian cancer (EOC). Patients enrolled in GOG-0218 with completed FACT-O TOI assessments at baseline and at least one follow-up assessment were eligible. Baseline FACT-O TOI scores were sorted by quartiles (Q1-4) and outcomes compared between Q1 and Q2-4 with log-rank statistic and multivariate Cox regression adjusting for age, stage, post-surgical residual disease size, and performance status (PS). Trends in FACT-O TOI scores from baseline to the latest follow-up assessment were evaluated for impact on intragroup (Q1 or Q2-4) outcome by log-rank analysis. Of 1152 eligible patients, 283 formed Q1 and 869 formed Q2-4. Mean baseline FACT-O TOI scores were 47.5 for Q1 vs. 74.7 for Q2-4 (P<0.001). Q1 compared to Q2-4 had worse median OS (37.5 vs. 45.6months, P=0.001) and worse median PFS (12.5 vs. 13.1months, P=0.096). Q2-4 patients had decreased risks of disease progression (HR 0.974, 95% CI 0.953-0.995, P=0.018), and death (HR 0.963, 95% CI 0.939-0.987, P=0.003) for each five-point increase in baseline FACT-O TOI. Improving versus worsening trends in FACT-O TOI scores were associated with longer median PFS (Q1: 12.7 vs. 8.6months, P=0.001; Q2-4: 16.7 vs. 11.1months, P<0.001) and median OS (Q1: 40.8 vs. 16months, P<0.001; Q2-4: 54.4 vs. 33.6months, P<0.001). Baseline FACT-O TOI scores were independently prognostic of PFS and OS while improving compared to worsening QOL was associated with significantly better PFS and OS in women with EOC. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular response assessed by {sup 68}Ga-DOTANOC and survival after {sup 90}Y microsphere therapy in patients with liver metastases from neuroendocrine tumours

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Filippi, Luca; Salvatori, Rita; Bagni, Oreste [Santa Maria Goretti Hospital, Department of Nuclear Medicine, Latina (Italy); Scopinaro, Francesco [Sant' Andrea Hospital, Department of Nuclear Medicine, Rome (Italy); Pelle, Giuseppe; Cianni, Roberto [Santa Maria Goretti Hospital, Department of Interventional Radiology, Latina (Italy); Schillaci, Orazio [University Tor Vergata, Department of Biomedicine and Prevention, Rome (Italy)

2016-03-15

We investigated the prognostic role of {sup 68}Ga-DOTANOC in patients affected by hepatic metastases from neuroendocrine tumours (NET) undergoing {sup 90}Y radioembolization ({sup 90}Y-RE). A group of 15 consecutive patients with unresectable NET liver metastases underwent {sup 68}Ga-DOTANOC PET at baseline and 6 weeks after {sup 90}Y-RE. Molecular response was defined as a reduction of >50 % in the tumour-to-spleen ratio (ΔT/S). The patients were divided into two groups (responders with ΔT/S >50 % and nonresponders with ΔT/S <50 %) Patients were followed up by imaging and laboratory tests every 3 months until death or for at least 36 months following {sup 90}Y-RE. Statistical analysis was performed to identify factors predicting overall survival (OS) and progression-free survival (PFS). A decrease in T/S ratio was seen in all patients on {sup 68}Ga-DOTANOC PET scans performed after {sup 90}Y-RE. Nine patients were classified as responders and six as nonresponders. The mean OS in all patients was 31.0 months. Responders had a significantly (p < 0.001) longer OS (mean 36.0 ± 2.5 months) and PFS (mean 29.7 ± 3.4 months) than nonresponders. In a multivariate analysis, none of the other examined variables including age, unilobar vs. bilobar locations, bilirubin levels, radiological response or the presence of extrahepatic disease significantly predicted patient outcome. Molecular response assessed with {sup 68}Ga-DOTANOC PET might be a useful predictor of survival in patients affected by NET liver metastases treated with {sup 90}Y-RE. (orig.)

Factors influencing survival and recurrence-free intervals after treatment of primary breast cancer

International Nuclear Information System (INIS)

O'Higgins, N.; Brady, H.R.; Clark, C.G.

1984-01-01

A retrospective analysis of 739 patients with breast cancer is presented. Factors influencing overall survival, recurrence-free interval and survival after first recurrence are analysed and discussed. None of the factors was affected by age or menopausal status at the time of presentation. Overall survival and recurrence-free intervals varied significantly with tumour size, extent of nodal spread and tumour site. Medially situated tumours, large tumours and extensive nodal spread were associated with earlier first recurrence and poor prognosis. No difference in survival or recurrence-free interval was observed between different surgical operations. Although overall survival was longer in patients who received post-operative radiotherapy, no significant differences in survival or disease-free intervals were noted when patients were standardised for operation or tumour stage. Survival after local recurrence was longer than survival after distant metastases, although the time of onset of local and distant disease followed an identical pattern. These results suggest that the tumour characteristics of size, site and nodal spread are important determinants of survival and recurrence-free interval in primary breast cancer. Local recurrence should be regarded as a manifestation of systemic disease. (author)

Predictive role of the overexpression for CXCR4, C-Met, and VEGF-C among breast cancer patients: A meta-analysis.

Science.gov (United States)

Wang, Fang; Li, Shanshan; Zhao, Yueguang; Yang, Kunxian; Chen, Minju; Niu, Heng; Yang, Jingyu; Luo, Ying; Tang, Wenru; Sheng, Miaomiao

2016-08-01

The overexpression of CXCR4, C-Met and VEGF-C present widely in breast tumors, they may be markers of resistance to treatment. However, the studies are still controversial. Thus, this meta-analysis aims to research the relationship between the overexpression of CXCR4, C-Met, VEGF-C and clinical prognosis among breast cancer patients. PubMed and EMBASE databases were searched for eligible literature. The outcomes of interest were progression-free survival (PFS), relapse-free survival (RFS) and overall survival (OS). All tests of statistical significance were two sided. A total of 7830 patients from 28 eligible studies were assessed. The overexpression of the CXCR4 and C-Met both implied significantly worse PFS compared with normal expression [HR = 2.56, 95% CI = 1.34-4.91, P = 0.005; and HR = 1.63 95% CI = 1.20-2.22, P = 0.002]. Meanwhile, if patients had high expression of CXCR4, they would have worse OS [HR = 2.56 95% CI = 1.52-4.31, P = 0.000]. However, the overexpression of C-Met did not relate to OS for breast cancer patients [HR = 1.16, 95% CI = 0.69-1.95, P = 0.570]. Meanwhile, no statistically significant different was observed with respect to PFS and OS between VEGF-C overexpression and normal expression [HR = 0.99, 95% CI = 0.64-1.52, P = 0.968; and HR = 0.76, 95% CI = 0.43-1.33, P = 0.333]. Our meta-analysis showed that CXCR4 and C-Met were efficient prognostic factors for breast cancer. Nevertheless, highly expressing VEGF-C was not related to progression-free survival and overall survival. Due to the small samples and insufficient date, further studies should be conducted to clarify the association between the overexpression of CXCR4 or C-Met or VEGF-C and the prognosis about breast cancer patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

A Prospective Phase 2 Trial of Reirradiation With Stereotactic Body Radiation Therapy Plus Cetuximab in Patients With Previously Irradiated Recurrent Squamous Cell Carcinoma of the Head and Neck

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Vargo, John A. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Ferris, Robert L. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Ohr, James [Division Medical Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Clump, David A. [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Davis, Kara S.; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T. [Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Bauman, Julie E.; Gibson, Michael K. [Division Medical Oncology, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania (United States); Branstetter, Barton F. [Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania (United States); Heron, Dwight E., E-mail: herond2@umpc.edu [Department of Radiation Oncology, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania (United States); Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania (United States)

2015-03-01

Purpose: Salvage options for unresectable locally recurrent, previously irradiated squamous cell carcinoma of the head and neck (rSCCHN) are limited. Although the addition of reirradiation may improve outcomes compared to chemotherapy alone, significant toxicities limit salvage reirradiation strategies, leading to suboptimal outcomes. We therefore designed a phase 2 protocol to evaluate the efficacy of stereotactic body radiation therapy (SBRT) plus cetuximab for rSCCHN. Methods and Materials: From July 2007 to March 2013, 50 patients >18 years of age with inoperable locoregionally confined rSCCHN within a previously irradiated field receiving ≥60 Gy, with a Zubrod performance status of 0 to 2, and normal hepatic and renal function were enrolled. Patients received concurrent cetuximab (400 mg/m{sup 2} on day −7 and then 250 mg/m{sup 2} on days 0 and +8) plus SBRT (40-44 Gy in 5 fractions on alternating days over 1-2 weeks). Primary endpoints were 1-year locoregional progression-free survival and National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 graded toxicity. Results: Median follow-up for surviving patients was 18 months (range: 10-70). The 1-year local PFS rate was 60% (95% confidence interval [CI]: 44%-75%), locoregional PFS was 37% (95% CI: 23%-53%), distant PFS was 71% (95% CI: 54%-85%), and PFS was 33% (95% CI: 20%-49%). The median overall survival was 10 months (95% CI: 7-16), with a 1-year overall survival of 40% (95% CI: 26%-54%). At last follow-up, 69% died of disease, 4% died with disease, 15% died without progression, 10% were alive without progression, and 2% were alive with progression. Acute and late grade 3 toxicity was observed in 6% of patients respectively. Conclusions: SBRT with concurrent cetuximab appears to be a safe salvage treatment for rSCCHN of short overall treatment time.

A Prospective Phase 2 Trial of Reirradiation With Stereotactic Body Radiation Therapy Plus Cetuximab in Patients With Previously Irradiated Recurrent Squamous Cell Carcinoma of the Head and Neck

International Nuclear Information System (INIS)

Vargo, John A.; Ferris, Robert L.; Ohr, James; Clump, David A.; Davis, Kara S.; Duvvuri, Umamaheswar; Kim, Seungwon; Johnson, Jonas T.; Bauman, Julie E.; Gibson, Michael K.; Branstetter, Barton F.; Heron, Dwight E.

2015-01-01

Purpose: Salvage options for unresectable locally recurrent, previously irradiated squamous cell carcinoma of the head and neck (rSCCHN) are limited. Although the addition of reirradiation may improve outcomes compared to chemotherapy alone, significant toxicities limit salvage reirradiation strategies, leading to suboptimal outcomes. We therefore designed a phase 2 protocol to evaluate the efficacy of stereotactic body radiation therapy (SBRT) plus cetuximab for rSCCHN. Methods and Materials: From July 2007 to March 2013, 50 patients >18 years of age with inoperable locoregionally confined rSCCHN within a previously irradiated field receiving ≥60 Gy, with a Zubrod performance status of 0 to 2, and normal hepatic and renal function were enrolled. Patients received concurrent cetuximab (400 mg/m 2 on day −7 and then 250 mg/m 2 on days 0 and +8) plus SBRT (40-44 Gy in 5 fractions on alternating days over 1-2 weeks). Primary endpoints were 1-year locoregional progression-free survival and National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 graded toxicity. Results: Median follow-up for surviving patients was 18 months (range: 10-70). The 1-year local PFS rate was 60% (95% confidence interval [CI]: 44%-75%), locoregional PFS was 37% (95% CI: 23%-53%), distant PFS was 71% (95% CI: 54%-85%), and PFS was 33% (95% CI: 20%-49%). The median overall survival was 10 months (95% CI: 7-16), with a 1-year overall survival of 40% (95% CI: 26%-54%). At last follow-up, 69% died of disease, 4% died with disease, 15% died without progression, 10% were alive without progression, and 2% were alive with progression. Acute and late grade 3 toxicity was observed in 6% of patients respectively. Conclusions: SBRT with concurrent cetuximab appears to be a safe salvage treatment for rSCCHN of short overall treatment time

Gemcitabine and docetaxel in relapsed and unresectable high-grade osteosarcoma and spindle cell sarcoma of bone

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Palmerini, E.; Jones, R. L.; Marchesi, E.; Paioli, A.; Cesari, M.; Longhi, A.; Meazza, C.; Coccoli, L.; Fagioli, F.; Asaftei, S.; Grignani, G.; Tamburini, A.; Pollack, S. M.; Picci, P.; Ferrari, S.

2016-01-01

Background Few new compounds are available for relapsed osteosarcoma. We retrospectively evaluated the activity of gemcitabine (G) plus docetaxel (D) in patients with relapsed high-grade osteosarcoma and high-grade spindle cell sarcoma of bone (HGS). Methods Patients receiving G 900?mg/m2 d 1, 8; D 75?mg/m2 d 8, every 21?days were eligible. Primary end-point: progression-free survival (PFS) at 4?months; secondary end-point: overall survival (OS) and response rate. Results Fifty-one patients w...

A Phase II Study of Weekly Docetaxel as Second-Line Chemotherapy in Patients With Metastatic Urothelial Carcinoma.

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Kim, Young Saing; Lee, Soon Il; Park, Se Hoon; Park, Silvia; Hwang, In Gyu; Lee, Sang-Cheol; Sun, Jong-Mu; Lee, Jeeyun; Lim, Ho Yeong

2016-02-01

The present multicenter phase II study evaluated the efficacy and safety of weekly docetaxel as second-line chemotherapy for metastatic urothelial carcinoma. Weekly docetaxel was well tolerated but demonstrated modest activity, with a response rate of 6%, a median progression-free survival (PFS) of 1.4 months, and a median overall survival (OS) of 8.3 months. The dichotomy between PFS and OS was likely associated with subsequent platinum-based chemotherapy received by 58% of the patients. Docetaxel is commonly used for second-line therapy for metastatic urothelial carcinoma (UC). However, myelosuppression is a substantial concern when the traditional 3-week docetaxel cycle is used. The present multicenter phase II study evaluated the efficacy and safety of weekly docetaxel as second-line chemotherapy for metastatic UC. Patients with progression after previous platinum-based chemotherapy for advanced or metastatic disease were treated with docetaxel 30 mg/m(2) on days 1 and 8 every 21 days. The primary endpoint was the response rate. The study enrolled 31 patients. Their median age was 64 years (range, 40-79 years). An Eastern Cooperative Oncology Group performance status of 1, liver metastasis, and a hemoglobin level chemotherapy had been administered for metastatic disease in 29 patients (94%). Although fatigue (13%) and anorexia (6%) were the most frequently observed grade 3 to 4 toxicities, the safety profiles were generally mild and manageable. Two patients (6%) achieved an objective response, which was maintained for 3.0 to 7.8 months. Eight patients experienced disease stabilization (disease control rate, 32%). The median progression-free survival (PFS) and overall survival (OS) were 1.4 months (95% confidence interval [CI], 1.3-1.6) and 8.3 months (95% CI, 5.9-10.6), respectively. A relatively long OS was associated with further salvage platinum-based chemotherapy (n = 18, 58%) showing an encouraging activity (response rate, 44%; median PFS, 4.0 months

ERGO: A pilot study of ketogenic diet in recurrent glioblastoma

Science.gov (United States)

RIEGER, JOHANNES; BÄHR, OLIVER; MAURER, GABRIELE D.; HATTINGEN, ELKE; FRANZ, KEA; BRUCKER, DANIEL; WALENTA, STEFAN; KÄMMERER, ULRIKE; COY, JOHANNES F.; WELLER, MICHAEL; STEINBACH, JOACHIM P.

2014-01-01

Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3–13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12–124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (pketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet. PMID:24728273

Retrospective Evaluation of Hairy Cell Leukemia Patients Treated with Three Different First-Line Treatment Modalities in the Last Two Decades: A Single-Center Experience

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Şeniz Öngören

2017-12-01

Full Text Available Objective: In this study, we retrospectively analyzed the clinical outcome, treatment responses, infectious complications, and survival rates of 71 hairy cell leukemia (HCL cases. Materials and Methods: Sixty-seven patients received a first-line treatment and 2-chlorodeoxyadenosine (cladribine-2-CdA was administered in 31 cases, 19 patients received interferon-alpha (INF-α, splenectomy was performed in 16 cases, and rituximab was used in one. Results: Although the highest overall response rate (ORR was observed in patients receiving 2-CdA upfront, ORRs were comparable in the 2-CdA, INF-α, and splenectomy subgroups. Relapse rates were significantly lower in patients who received first-line 2-CdA. The progression-free survival (PFS rate with 2-CdA was significantly higher than in patients with INF-α and splenectomy, but we found similar overall survival rates with all three upfront treatment modalities. Infections including tuberculosis were a major problem. Conclusion: Although purine analogues have improved the ORRs and PFS, there is still much progress to make with regard to overall survival and relapsed/refractory disease in patients with HCL.

Radiological response and survival in locally advanced non-small-cell lung cancer patients treated with three-drug induction chemotherapy followed by radical local treatment

Directory of Open Access Journals (Sweden)

Bonanno L

2016-06-01

Full Text Available Laura Bonanno,1 Giulia Zago,1 Giuseppe Marulli,2 Paola Del Bianco,3 Marco Schiavon,2 Giulia Pasello,1 Valentina Polo,1,4 Fabio Canova,1 Fabrizio Tonetto,5 Lucio Loreggian,5 Federico Rea,2 PierFranco Conte,1,4 Adolfo Favaretto1 1Medical Oncology Unit 2, Veneto Institute of Oncology IOV-IRCCS, 2Thoracic Surgery Department, University of Padova, 3Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology IOV-IRCCS, 4Department of Surgery, Oncology and Gastroenterology, University of Padova, 5Radiotherapy Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy Objectives: If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs. No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. Methods: We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1, paclitaxel (200 mg/m2, d1, and gemcitabine (1,000 mg/m2 d1, 8 for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS and overall survival (OS were correlated to response, surgery, and clinical features. Results: In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors–7th edition staging system. A total of 36 (62% patients achieved partial response (PR, and six (10% progressions were recorded. Grade 3–4 hematological toxicity was observed in 36 (62% cases. After chemotherapy, 37 (64% patients underwent surgery

Predictive value of modeled AUC(AFP-hCG), a dynamic kinetic parameter characterizing serum tumor marker decline in patients with nonseminomatous germ cell tumor.

Science.gov (United States)

You, Benoit; Fronton, Ludivine; Boyle, Helen; Droz, Jean-Pierre; Girard, Pascal; Tranchand, Brigitte; Ribba, Benjamin; Tod, Michel; Chabaud, Sylvie; Coquelin, Henri; Fléchon, Aude

2010-08-01

The early decline profile of alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) in patients with nonseminomatous germ cell tumors (NSGCT) treated with chemotherapy may be related to the risk of relapse. We assessed the predictive values of areas under the curve of hCG (AUC(hCG)) and AFP (AUC(AFP)) of modeled concentration-time equations on progression-free survival (PFS). Single-center retrospective analysis of hCG and AFP time-points from 65 patients with IGCCCG intermediate-poor risk NSGCT treated with 4 cycles of bleomycin-etoposide-cisplatin (BEP). To determine AUC(hCG) and AUC(AFP) for D0-D42, AUCs for D0-D7 were calculated using the trapezoid rule and AUCs for D7-D42 were calculated using the mathematic integrals of equations modeled with NONMEM. Combining AUC(AFP) and AUC(hCG) enabled us to define 2 predictive groups: namely, patients with favorable and unfavorable AUC(AFP-hCG). Survival analyses and ROC curves assessed the predictive values of AUC(AFP-hCG) groups regarding progression-free survival (PFS) and compared them with those of half-life (HL) and time-to-normalization (TTN). Mono-exponential models best fit the patterns of marker decreases. Patients with a favorable AUC(AFP-hCG) had a significantly better PFS (100% vs 71.5%, P = .014). ROC curves confirmed the encouraging predictive accuracy of AUC(AFP-hCG) against HL or TTN regarding progression risk (ROC AUCs = 79.6 vs 71.9 and 70.2 respectively). Because of the large number of patients with missing data, multivariate analysis could not be performed. AUC(AFP-hCG) is a dynamic parameter characterizing tumor marker decline in patients with NSGCT during BEP treatment. Its value as a promising predictive factor should be validated. Copyright 2010 Elsevier Inc. All rights reserved.

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

International Nuclear Information System (INIS)

Vainshtein, Jeffrey M.; Schipper, Matthew; Zalupski, Mark M.; Lawrence, Theodore S.; Abrams, Ross; Francis, Isaac R.; Khan, Gazala; Leslie, William; Ben-Josef, Edgar

2013-01-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

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Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Schipper, Matthew [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Zalupski, Mark M. [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Lawrence, Theodore S. [Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan (United States); Abrams, Ross [Department of Radiation Oncology, Rush Medical Center, Chicago, Illinois (United States); Francis, Isaac R. [Department of Radiology, University of Michigan, Ann Arbor, Michigan (United States); Khan, Gazala [Division of Hematology Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); Leslie, William [Division of Hematology Oncology, Department of Internal Medicine, Rush Medical Center, Chicago, Illinois (United States); Ben-Josef, Edgar [Department of Radiation Oncology, University of Pennsylvania, Philadelphia, Pennsylvania (United States)

2013-05-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factors on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression

Predictors of biochemical failure in patients undergoing prostate whole-gland salvage cryotherapy: a novel risk stratification model.

Science.gov (United States)

Spiess, Philippe E; Levy, David A; Mouraviev, Vladimir; Pisters, Louis L; Jones, J Stephen

2013-08-01

What's known on the subject? and what does the study add?: Previous studies have identified the most important prognostic factors of the likely outcomes of salvage prostate whole-gland ablation, including initial clinical stage, biopsy Gleason score, and PSA (total and doubling time). There is potential for further optimization of candidate selection for salvage cryoablation with curative intent and nadir PSA achieved after whole-gland cryotherapy may provide additional prognostic value. The study shows that the most important prognostic factors of biochemical progression-free survival for patients who have undergone whole-gland salvage prostate cryotherapy are nadir PSA achieved after therapy and pre-therapy biopsy Gleason score. Based on these two prognostic variables, we have identified risk stratification groups (low, intermediate and high) which help predict the expected outcomes of salvage whole-gland prostate cryotherapy in a given patient. This risk stratification constitutes a useful clinical tool in defining which patients maybe best suited for this local salvage treatment method. To assess the prognostic variables predicting the risk of biochemical progression-free survival (bPFS) after salvage prostate whole-gland cryotherapy using the Phoenix definition of bPFS. A total of 132 patients underwent prostate whole-gland salvage cryotherapy with curative intent. No patient underwent neoadjuvant/adjuvant hormonal ablative therapy, and all had extended post-salvage prostate-specific antigen (PSA) follow-up data. Cox univariate and multivariate logistic regression analyses of potential predictors of bPFS were conducted. Kaplan-Meier analyses of bPFS was also performed. At a mean (range) follow-up of 4.3 (0.9-12.7) years, the median (range) post-cryotherapy nadir PSA achieved was 0.17 (0-33.9) ng/mL. On multivariate analysis, predictors of bPFS were nadir PSA post-cryotherapy and pre-salvage biopsy Gleason score (P 2.5 ng/mL or biopsy Gleason score ≥ 7, with

Zone-size nonuniformity of 18F-FDG PET regional textural features predicts survival in patients with oropharyngeal cancer.

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Cheng, Nai-Ming; Fang, Yu-Hua Dean; Lee, Li-yu; Chang, Joseph Tung-Chieh; Tsan, Din-Li; Ng, Shu-Hang; Wang, Hung-Ming; Liao, Chun-Ta; Yang, Lan-Yan; Hsu, Ching-Han; Yen, Tzu-Chen

2015-03-01

The question as to whether the regional textural features extracted from PET images predict prognosis in oropharyngeal squamous cell carcinoma (OPSCC) remains open. In this study, we investigated the prognostic impact of regional heterogeneity in patients with T3/T4 OPSCC. We retrospectively reviewed the records of 88 patients with T3 or T4 OPSCC who had completed primary therapy. Progression-free survival (PFS) and disease-specific survival (DSS) were the main outcome measures. In an exploratory analysis, a standardized uptake value of 2.5 (SUV 2.5) was taken as the cut-off value for the detection of tumour boundaries. A fixed threshold at 42 % of the maximum SUV (SUVmax 42 %) and an adaptive threshold method were then used for validation. Regional textural features were extracted from pretreatment (18)F-FDG PET/CT images using the grey-level run length encoding method and grey-level size zone matrix. The prognostic significance of PET textural features was examined using receiver operating characteristic (ROC) curves and Cox regression analysis. Zone-size nonuniformity (ZSNU) was identified as an independent predictor of PFS and DSS. Its prognostic impact was confirmed using both the SUVmax 42 % and the adaptive threshold segmentation methods. Based on (1) total lesion glycolysis, (2) uniformity (a local scale texture parameter), and (3) ZSNU, we devised a prognostic stratification system that allowed the identification of four distinct risk groups. The model combining the three prognostic parameters showed a higher predictive value than each variable alone. ZSNU is an independent predictor of outcome in patients with advanced T-stage OPSCC, and may improve their prognostic stratification.

Evolution of Randomized Trials in Advanced/Metastatic Soft Tissue Sarcoma: End Point Selection, Surrogacy, and Quality of Reporting.

Science.gov (United States)

Zer, Alona; Prince, Rebecca M; Amir, Eitan; Abdul Razak, Albiruni

2016-05-01

Randomized controlled trials (RCTs) in soft tissue sarcoma (STS) have used varying end points. The surrogacy of intermediate end points, such as progression-free survival (PFS), response rate (RR), and 3-month and 6-month PFS (3moPFS and 6moPFS) with overall survival (OS), remains unknown. The quality of efficacy and toxicity reporting in these studies is also uncertain. A systematic review of systemic therapy RCTs in STS was performed. Surrogacy between intermediate end points and OS was explored using weighted linear regression for the hazard ratio for OS with the hazard ratio for PFS or the odds ratio for RR, 3moPFS, and 6moPFS. The quality of reporting for efficacy and toxicity was also evaluated. Fifty-two RCTs published between 1974 and 2014, comprising 9,762 patients, met the inclusion criteria. There were significant correlations between PFS and OS (R = 0.61) and between RR and OS (R = 0.51). Conversely, there were nonsignificant correlations between 3moPFS and 6moPFS with OS. A reduction in the use of RR as the primary end point was observed over time, favoring time-based events (P for trend = .02). In 14% of RCTs, the primary end point was not met, but the study was reported as being positive. Toxicity was comprehensively reported in 47% of RCTs, whereas 14% inadequately reported toxicity. In advanced STS, PFS and RR seem to be appropriate surrogates for OS. There is poor correlation between OS and both 3moPFS and 6moPFS. As such, caution is urged with the use of these as primary end points in randomized STS trials. The quality of toxicity reporting and interpretation of results is suboptimal. © 2016 by American Society of Clinical Oncology.

High-dose therapy and autologous transplantation for lymphoma: the Peter MacCallum Cancer institute experience

International Nuclear Information System (INIS)

Dowling, A.J.; Prince, H.M.; Wolf, M.; Januszewicz, H.; Seymour, J.F.; Gates, P.; Wirth, A.; Juneja, S.; Smith, J.G.

2001-01-01

High-dose therapy (HDT) with autologous bone marrow or blood cell transplantation for the treatment of lymphoma commenced at Peter MacCallum Cancer Institute in 1986. To examine the patient characteristics and outcomes of patients with non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) treated with HDT and autologous transplantation at our Institute in the first 10 years of the service (1986-95). A retrospective analysis was performed examining patient characteristics, prior chemotherapy regimens, pretransplant disease status, HDT regimen, source of stem cells, time for haematopoietic recovery, complications of transplantation, response rates, overall survival (OS) and progression-free survival (PFS). Sixty-seven patients with NHL were treated with an estimated 5-year OS rate of 44% (95% confidence interval (CI) 32-56%) and PFS rate of 34% (95% CI 21-44%). Factors independently predictive of an unfavourable PFS on multivariate analyses were presence of constitutional symptoms at transplant (P < 0.002) and chemotherapy-resistant disease at transplant (P= 0.02). Twenty-three patients with HD were treated with a 5-year predicted OS rate of 74% (95% CI 56-92%) and PFS rate of 57% (95% CI 36-77%).There was no difference in PFS for HD patients who relapsed either within 12 months of completion of front-line therapy or after this time (P =0.5). The transplant-related mortality for the entire cohort was 17%, with a progressive decrease over time. HDT with autologous transplantation achieves durable PFS and OS in patients with lymphoma. Improved patient selection, therapy modifications according to prognostic factors and ongoing improvements in supportive care should improve outcomes further

FDG-PET/ceCT is useful to predict recurrence of Pseudomyxoma peritonei

International Nuclear Information System (INIS)

Dubreuil, Julien; Skanjeti, Andrea; Giammarile, Francesco; Rousset, Pascal; Bakrin, Naoual; Passot, Guillaume; Isaac, Sylvie; Glehen, Olivier

2016-01-01

Pseudomyxoma peritonei (PMP) is a rare peritoneal neoplasm originating from appendicular tumours. There is no consolidated data available in the literature about the precise role of [ 18 F] fluorodesoxy-D-glucose Positron Emission Tomography / contrast enhanced Computed Tomography (FDG-PET/ceCT). The aim of this study was to evaluate the correlation between preoperative FDG-PET/ceCT (qualitative and semi-quantitative assessment) and progression free survival (PFS) of patients treated for PMP. All patients scheduled for PMP treatment by cytoreductive unicentric surgery, intraperitoneal chemotherapy (HIPEC), and who underwent a FDG-PET/ceCT between February 2008 and January 2014, were included. No previous treatment was performed (except biopsy or appendectomy). FDG-PET/ceCT was interpreted by two nuclear physicians in consensus. Positive FDG-PET/ceCT scans were further labelled in diffuse disease and poly/mono focal disease. SUVmax was measured based on post-operative reports. The Peritoneal Cancer Index (PCI) and Completeness of CytoReduction Score (CCR) were assessed after surgery. Fifty-six patients were included in this study, with a mean age of 56-years-old and a mean follow-up of 29.3 months. SUVmax, with a cut-off at 2.02, was predictive for the PFS on multivariate analysis. No differences were observed between diffuse disease and focal disease on PFS for progression free survival, PCI, and SUVmax (p = 0.1). Post-operative CCR was not significantly correlated with SUVmax or FDG-PET/ceCT qualitative assessment. SUVmax on preoperative FDG-PET/ceCT was an independent predictive factor for PFS in PMP. Further studies are needed to explore if FDG-PET/ceCT could potentially predict post-operative CCR. (orig.)

Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer

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Morris, W. James, E-mail: jmorris@bccancer.bc.ca [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Tyldesley, Scott [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Rodda, Sree [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); Halperin, Ross [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Centre for the Southern Interior, Vancouver, British Columbia (Canada); Pai, Howard [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Island Centre, Vancouver, British Columbia (Canada); McKenzie, Michael; Duncan, Graeme [Department of Surgery, University of British Columbia, Vancouver, British Columbia (Canada); BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Morton, Gerard [Department of Radiation Oncology, University of Toronto, Sunnybrook Health Sciences Centre, Toronto, Ontario (Canada); Hamm, Jeremy [Department of Population Oncology, BC Cancer Agency, Vancouver, British Columbia (Canada); Murray, Nevin [BC Cancer Agency–Vancouver Centre, Vancouver, British Columbia (Canada); Department of Medicine, University of British Columbia, Vancouver, British Columbia (Canada)

2017-06-01

Purpose: To report the primary endpoint of biochemical progression-free survival (b-PFS) and secondary survival endpoints from ASCENDE-RT, a randomized trial comparing 2 methods of dose escalation for intermediate- and high-risk prostate cancer. Methods and Materials: ASCENDE-RT enrolled 398 men, with a median age of 68 years; 69% (n=276) had high-risk disease. After stratification by risk group, the subjects were randomized to a standard arm with 12 months of androgen deprivation therapy, pelvic irradiation to 46 Gy, followed by a dose-escalated external beam radiation therapy (DE-EBRT) boost to 78 Gy, or an experimental arm that substituted a low-dose-rate prostate brachytherapy (LDR-PB) boost. Of the 398 trial subjects, 200 were assigned to DE-EBRT boost and 198 to LDR-PB boost. The median follow-up was 6.5 years. Results: In an intent-to-treat analysis, men randomized to DE-EBRT were twice as likely to experience biochemical failure (multivariable analysis [MVA] hazard ratio [HR] 2.04; P=.004). The 5-, 7-, and 9-year Kaplan-Meier b-PFS estimates were 89%, 86%, and 83% for the LDR-PB boost versus 84%, 75%, and 62% for the DE-EBRT boost (log-rank P<.001). The LDR-PB boost benefited both intermediate- and high-risk patients. Because the b-PFS curves for the treatment arms diverge sharply after 4 years, the relative advantage of the LDR-PB should increase with longer follow-up. On MVA, the only variables correlated with reduced overall survival were age (MVA HR 1.06/y; P=.004) and biochemical failure (MVA HR 6.30; P<.001). Although biochemical failure was associated with increased mortality and randomization to DE-EBRT doubled the rate of biochemical failure, no significant overall survival difference was observed between the treatment arms (MVA HR 1.13; P=.62). Conclusions: Compared with 78 Gy EBRT, men randomized to the LDR-PB boost were twice as likely to be free of biochemical failure at a median follow-up of 6.5 years.

Single-institution long-term outcomes for patients receiving nonmyeloablative conditioning hematopoeitic cell transplantation for chronic lymphocytic leukemia and follicular lymphoma

DEFF Research Database (Denmark)

Mortensen, Bo K; Petersen, Søren; Kornblit, Brian

2012-01-01

Non-myeloablative conditioning hematopoietic cell transplantation (NMC-HCT) has improved the treatment of chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL). In a cohort of 85 patients (45 with CLL and 40 with FL), we observed 5-yr overall survival (OS) and progression-free survival...... (PFS) of 53% and 38% in the CLL group and 81% and 76% in the FL group. In the both the CLL group and the FL group, a strong trend toward better OS and PFS was observed among patients in complete remission (CR) at HCT. Within the FL group, sixteen patients had at one or more time points in their disease...... treatment that can provide long-term survival in elderly, heavily pretreated patients with FL and CLL. Especially patients with FL, and also transformed FL, seemed to have a great benefit of NMC-HCT, and CR at the time of HCT was an important prognostic factor....

Regorafenib for advanced gastrointestinal stromal tumors following imatinib and sunitinib treatment: a subgroup analysis evaluating Japanese patients in the phase III GRID trial.

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Komatsu, Yoshito; Doi, Toshihiko; Sawaki, Akira; Kanda, Tatsuo; Yamada, Yasuhide; Kuss, Iris; Demetri, George D; Nishida, Toshirou

2015-10-01

The randomized, double-blind, placebo-controlled GRID trial tested the oral multikinase inhibitor regorafenib in 199 patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib, and showed a significant improvement in progression-free survival (PFS) versus placebo [hazard ratio (HR) 0.27; 95 % confidence interval (CI) 0.19-0.39; p regorafenib 160 mg once daily with matching placebo, in combination with best supportive care. The primary study endpoint was progression-free survival (PFS); safety was evaluated through the incidence of adverse events (AEs). Seventeen Japanese patients were randomized to regorafenib (n = 12) or placebo (n = 5). Patient demographics were consistent with those of the overall study population. PFS was significantly longer with regorafenib than placebo (HR 0.08; 95 % CI 0.02-0.45; p = 0.000164). Centrally assessed disease control rates were 58 % and 20 % in the regorafenib and placebo groups, respectively (p = 0.080796). Treatment-related adverse events (AEs) were reported in all regorafenib-treated patients and 60 % of placebo recipients; the most frequent AE was hand-foot skin reaction (HFSR) (92 % versus 20 %, respectively). Regorafenib showed efficacy and a manageable safety profile in Japanese patients with advanced GIST, consistent with the overall GRID study population. AEs, such as HFSR and maculopapular rash, were observed more frequently in Japanese patients. Although dose modification was frequently reported, only one patient with hepatic failure discontinued regorafenib because of AEs.

Prostate specific antigen (PSA) kinetic as a prognostic factor in metastatic prostate cancer receiving androgen deprivation therapy: systematic review and meta-analysis.

Science.gov (United States)

Afriansyah, Andika; Hamid, Agus Rizal Ardy Hariandy; Mochtar, Chaidir Arif; Umbas, Rainy

2018-01-01

Aim: Metastatic prostate cancer (mPCa) has a poor outcome with median survival of two to five years. The use of androgen deprivation therapy (ADT) is a gold standard in management of this stage.  Aim of this study is to analyze the prognostic value of PSA kinetics of patient treated with hormonal therapy related to survival from several published studies Method: Systematic review and meta-analysis was performed using literature searching in the electronic databases of MEDLINE, Science Direct, and Cochrane Library. Inclusion criteria were mPCa receiving ADT, a study analyzing Progression Free Survival (PFS), Overall Survival (OS), or Cancer Specific Survival (CSS) and prognostic factor of survival related to PSA kinetics (initial PSA, PSA nadir, and time to achieve nadir (TTN)). The exclusion criteria were metastatic castration resistant of prostate cancer (mCRPC) and non-metastatic disease. Generic inverse variance method was used to combine hazard ratio (HR) within the studies. Meta-analysis was performed using Review Manager 5.2 and a p-value PSA and PFS. In addition, there was no association between initial PSA and CSS/ OS. We found association of reduced PFS (HR 2.22; 95% CI 1.82 to 2.70) and OS/ CSS (HR 3.31; 95% CI 2.01-5.43) of patient with high PSA nadir. Shorter TTN was correlated with poor result of survival either PFS (HR 2.41; 95% CI 1.19 - 4.86) or CSS/ OS (HR 1.80; 95%CI  1.42 - 2.30) Conclusion: Initial PSA before starting ADT do not associated with survival in mPCa.  There is association of PSA nadir and TTN with survival.

Androgen-deprivation therapy does not impact cause-specific or overall survival after permanent prostate brachytherapy

International Nuclear Information System (INIS)

Merrick, Gregory S.; Butler, Wayne M.; Wallner, Kent E.; Galbreath, Robert W.; Allen, Zachariah A. M.S.; Adamovich, Edward

2006-01-01

Purpose: To determine if androgen-deprivation therapy (ADT) has an impact on cause-specific, biochemical progression-free, or overall survival after prostate brachytherapy. Methods and Materials: From April 1995 through June 2002, 938 consecutive patients underwent brachytherapy for clinical Stage T1b to T3a (2002 AJCC) prostate cancer. All patients underwent brachytherapy more than 3 years before analysis. A total of 382 patients (40.7%) received ADT with a duration of 6 months or less in 277 and more than 6 months in 105. The median follow-up was 5.4 years. Multiple clinical, treatment, and dosimetric parameters were evaluated as predictors of cause-specific, biochemical progression-free, and overall survival. Results: The 10-year cause-specific, biochemical progression-free, and overall survival rates for the entire cohort were 96.4%, 95.9%, and 78.1%, respectively. Except for biochemical progression-free survival in high-risk patients, ADT did not statistically impact any of the three survival categories. A Cox linear-regression analysis demonstrated that Gleason score was the best predictor of cause-specific survival, whereas percent-positive biopsies, prostate volume, and risk group predicted for biochemical progression-free survival. Patient age and tobacco use were the strongest predictors of overall survival. One hundred two patients have died, with 80 of the deaths a result of cardiovascular disease (54) and second malignancies (26). To date, only 12 patients have died of metastatic prostate cancer. Conclusions: After brachytherapy, androgen-deprivation therapy did not have an impact on cause-specific or overall survival for any risk group; however, ADT had a beneficial effect on biochemical progression-free survival in high-risk patients. Cardiovascular disease and second malignancies far outweighed prostate cancer as competing causes of death

PTEN expression as a predictor for the response to trastuzumab-based therapy in Her-2 overexpressing metastatic breast cancer.

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Daphne Gschwantler-Kaulich

Full Text Available Even though trastuzumab is an effective therapy in early stage Her-2+ breast cancer, 40-50% of advanced Her-2+ breast cancer patients develop trastuzumab resistance. A potential resistance mechanism is aberrant downstream signal transmission due to loss of phosphatase and tensin homologue (PTEN. This study investigated the relationship between the expression of PTEN and trastuzumab response in Her-2 overexpressing metastatic breast cancer patients.Between 2000 and 2007, 164 patients with Her-2+ metastatic breast cancer received trastuzumab-based therapy in our institution. We analyzed PTEN status by immunohistochemistry of 115 available tumor tissues and analyzed associations with other histopathological parameters, response rate, progression free survival (PFS and overall survival (OS with a median follow-up of 60 months.Eighty patients were PTEN positive (69.6% and 35 patients PTEN negative (30.4%. We found a significant association of the expression of PTEN and p53 (p = 0.041, while there was no association with grading, hormone receptor status, IGFR or MIB. We found significantly more cases with progressive disease under trastuzumab-based therapy in patients with PTEN positive breast cancers (p = 0.018, while there was no significant correlation with PFS or OS.In Her-2-positive metastatic breast cancers, PTEN positivity was significantly associated with progressive disease, but not with PFS or OS.

Greater Biopsy Core Number Is Associated With Improved Biochemical Control in Patients Treated With Permanent Prostate Brachytherapy

International Nuclear Information System (INIS)

Bittner, Nathan; Merrick, Gregory S.; Galbreath, Robert W.; Butler, Wayne M.; Adamovich, Edward; Wallner, Kent E.

2010-01-01

Purpose: Standard prostate biopsy schemes underestimate Gleason score in a significant percentage of cases. Extended biopsy improves diagnostic accuracy and provides more reliable prognostic information. In this study, we tested the hypothesis that greater biopsy core number should result in improved treatment outcome through better tailoring of therapy. Methods and Materials: From April 1995 to May 2006, 1,613 prostate cancer patients were treated with permanent brachytherapy. Patients were divided into five groups stratified by the number of prostate biopsy cores (≤6, 7-9, 10-12, 13-20, and >20 cores). Biochemical progression-free survival (bPFS), cause-specific survival (CSS), and overall survival (OS) were evaluated as a function of core number. Results: The median patient age was 66 years, and the median preimplant prostate-specific antigen was 6.5 ng/mL. The overall 10-year bPFS, CSS, and OS were 95.6%, 98.3%, and 78.6%, respectively. When bPFS was analyzed as a function of core number, the 10-year bPFS for patients with >20, 13-20, 10-12, 7-9 and ≤6 cores was 100%, 100%, 98.3%, 95.8%, and 93.0% (p < 0.001), respectively. When evaluated by treatment era (1995-2000 vs. 2001-2006), the number of biopsy cores remained a statistically significant predictor of bPFS. On multivariate analysis, the number of biopsy cores was predictive of bPFS but did not predict for CSS or OS. Conclusion: Greater biopsy core number was associated with a statistically significant improvement in bPFS. Comprehensive regional sampling of the prostate may enhance diagnostic accuracy compared to a standard biopsy scheme, resulting in better tailoring of therapy.

Zone-size nonuniformity of {sup 18}F-FDG PET regional textural features predicts survival in patients with oropharyngeal cancer

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Cheng, Nai-Ming [Chang Gung Memorial Hospital and Chang Gung University, Departments of Nuclear Medicine, Taiyuan (China); Chang Gung Memorial Hospital, Department of Nuclear Medicine, Keelung (China); National Tsing Hua University, Department of Biomedical Engineering and Environmental Sciences, Hsinchu (China); Fang, Yu-Hua Dean [Chang Gung University, Department of Electrical Engineering, Taiyuan (China); Lee, Li-yu [Chang Gung University College of Medicine, Department of Pathology, Chang Gung Memorial Hospital, Taoyuan (China); Chang, Joseph Tung-Chieh; Tsan, Din-Li [Chang Gung University College of Medicine, Department of Radiation Oncology, Chang Gung Memorial Hospital, Taoyuan (China); Ng, Shu-Hang [Chang Gung University College of Medicine, Department of Diagnostic Radiology, Chang Gung Memorial Hospital, Taoyuan (China); Wang, Hung-Ming [Chang Gung University College of Medicine, Division of Hematology/Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Taoyuan (China); Liao, Chun-Ta [Chang Gung University College of Medicine, Department of Otolaryngology-Head and Neck Surgery, Chang Gung Memorial Hospital, Taoyuan (China); Yang, Lan-Yan [Chang Gung Memorial Hospital, Biostatistics Unit, Clinical Trial Center, Taoyuan (China); Hsu, Ching-Han [National Tsing Hua University, Department of Biomedical Engineering and Environmental Sciences, Hsinchu (China); Yen, Tzu-Chen [Chang Gung Memorial Hospital and Chang Gung University, Departments of Nuclear Medicine, Taiyuan (China); Chang Gung University College of Medicine, Department of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial Hospital, Taipei (China)

2014-10-23

The question as to whether the regional textural features extracted from PET images predict prognosis in oropharyngeal squamous cell carcinoma (OPSCC) remains open. In this study, we investigated the prognostic impact of regional heterogeneity in patients with T3/T4 OPSCC. We retrospectively reviewed the records of 88 patients with T3 or T4 OPSCC who had completed primary therapy. Progression-free survival (PFS) and disease-specific survival (DSS) were the main outcome measures. In an exploratory analysis, a standardized uptake value of 2.5 (SUV 2.5) was taken as the cut-off value for the detection of tumour boundaries. A fixed threshold at 42 % of the maximum SUV (SUV{sub max} 42 %) and an adaptive threshold method were then used for validation. Regional textural features were extracted from pretreatment {sup 18}F-FDG PET/CT images using the grey-level run length encoding method and grey-level size zone matrix. The prognostic significance of PET textural features was examined using receiver operating characteristic (ROC) curves and Cox regression analysis. Zone-size nonuniformity (ZSNU) was identified as an independent predictor of PFS and DSS. Its prognostic impact was confirmed using both the SUV{sub max} 42 % and the adaptive threshold segmentation methods. Based on (1) total lesion glycolysis, (2) uniformity (a local scale texture parameter), and (3) ZSNU, we devised a prognostic stratification system that allowed the identification of four distinct risk groups. The model combining the three prognostic parameters showed a higher predictive value than each variable alone. ZSNU is an independent predictor of outcome in patients with advanced T-stage OPSCC, and may improve their prognostic stratification. (orig.)

Alga-Produced Cholera Toxin-Pfs25 Fusion Proteins as Oral Vaccines

Science.gov (United States)

Gregory, James A.; Topol, Aaron B.; Doerner, David Z.

2013-01-01

Infectious diseases disproportionately affect indigent regions and are the greatest cause of childhood mortality in developing countries. Practical, low-cost vaccines for use in these countries are paramount to reducing disease burdens and concomitant poverty. Algae are a promising low-cost system for producing vaccines that can be orally delivered, thereby avoiding expensive purification and injectable delivery. We engineered the chloroplast of the eukaryotic alga Chlamydomonas reinhardtii to produce a chimeric protein consisting of the 25-kDa Plasmodium falciparum surface protein (Pfs25) fused to the β subunit of the cholera toxin (CtxB) to investigate an alga-based whole-cell oral vaccine. Pfs25 is a promising malaria transmission-blocking vaccine candidate that has been difficult to produce in traditional recombinant systems due to its structurally complex tandem repeats of epidermal growth factor-like domains. The noncatalytic CtxB domain of the cholera holotoxin assembles into a pentameric structure and acts as a mucosal adjuvant by binding GM1 ganglioside receptors on gut epithelial cells. We demonstrate that CtxB-Pfs25 accumulates as a soluble, properly folded and functional protein within algal chloroplasts, and it is stable in freeze-dried alga cells at ambient temperatures. In mice, oral vaccination using freeze-dried algae that produce CtxB-Pfs25 elicited CtxB-specific serum IgG antibodies and both CtxB- and Pfs25-specific secretory IgA antibodies. These data suggest that algae are a promising system for production and oral delivery of vaccine antigens, but as an orally delivered adjuvant, CtxB is best suited for eliciting secretory IgA antibodies for vaccine antigens against pathogens that invade mucosal surfaces using this strategy. PMID:23603678

The Use of Re-irradiation in Locally Recurrent, Non-metastatic Rectal Cancer.

Science.gov (United States)

Susko, Matthew; Lee, Jason; Salama, Joseph; Thomas, Samantha; Uronis, Hope; Hsu, David; Migaly, John; Willett, Christopher; Czito, Brian; Palta, Manisha

2016-10-01

The optimal approach to patients with locally recurrent, non-metastatic rectal cancer is unclear. This study evaluates the outcomes and toxicity associated with pelvic re-irradiation. Patients undergoing re-irradiation for locally recurrent, non-metastatic, rectal cancer between 2000 and 2014 were identified. Acute and late toxicities were assessed using common terminology criteria for adverse events version 4.0. Disease-related endpoints included palliation of local symptoms, surgical outcomes, and local progression-free survival (PFS), distant PFS and overall survival (OS) using the Kaplan-Meier method. Thirty-three patients met the criteria for inclusion in this study. Two (6 %) experienced early grade 3+ toxicity and seven (21 %) experienced late grade 3+ toxicity. Twenty-three patients presented with symptomatic local recurrence and 18 (78 %) reported symptomatic relief. Median local PFS was 8.7 (95 % CI 3.8-15.2) months, with a 2-year rate of 15.7 % (4.1-34.2), and median time to distant progression was 4.4 (2.2-33.3) months, with a 2-year distant PFS rate of 38.9 % (20.1-57.3). Median OS time for patients was 23.1 (11.1-33.0) months. Of the 14 patients who underwent surgery, median survival was 32.3 (13.8-48.0) months compared with 13.3 (2.2-33.0) months in patients not undergoing surgery (p = 0.10). A margin-negative (R0) resection was achieved in 10 (71 %) of the surgeries. Radiation treatment modality (intensity-modulated radiation therapy, three-dimensional conformal radiotherapy, intraoperative radiation therapy) did not influence local or distant PFS or OS. Re-irradiation is a beneficial treatment modality for the management of locally recurrent, non-metastatic rectal cancer. It is associated with symptom improvement, low rates of toxicity, and similar benefits among radiation modalities.

Single-dose radiosurgical treatment for hepatic metastases - therapeutic outcome of 138 treated lesions from a single institution

International Nuclear Information System (INIS)

Habermehl, Daniel; Herfarth, Klaus K; Bermejo, Justo Lorenzo; Hof, Holger; Rieken, Stefan; Kuhn, Sabine; Welzel, Thomas; Debus, Jürgen; Combs, Stephanie E

2013-01-01

Local ablative therapies such as stereotactically guided single-dose radiotherapy or helical intensity-modulated radiotherapy (tomotherapy) with high single-doses are successfully applied in many centers in patients with liver metastasis not suitable for surgical resection. This study presents results from more than 10 years of clinical experience and evaluates long-term outcome and efficacy of this therapeutic approach. From 1997 to 2009 a total of 138 intrahepatic tumors of 90 patients were irradiated with single doses of 17 to 30 Gy (median dose 24 Gy). Median age of the patients was 64 years (range 31–89 years). Most frequent underlying tumor histologies were colorectal adenocarcinoma (70 lesions) and breast cancer (27 lesions). In 35 treatment sessions multiple targets were simultaneously irradiated (up to four lesions at once). Local progression-free (PFS) and overall survival (OS) after treatment were investigated using uni- and multiple survival regression models. Median overall survival of all patients was 24.3 months. Local PFS was 87%, 70% and 59% after 6, 12 and 18 months, respectively. Median time to local progression was 25.5 months. Patients with a single lesion and no further metastases at time of RT had a favorable median PFS of 43.1 months according to the Kaplan-Meier estimator. The type of tumor showed a statistical significant influence on local PFS, with a better prognosis for breast cancer histology than for colorectal carcinoma in uni- and multiple regression analysis (p = 0.05). Multiple regression analysis revealed no influence of planning target volume (PTV), patient age and radiation dose on local PFS. Treatment was well tolerated with no severe adverse events. This study confirms safety of SBRT in liver lesions, with 6- and 12 months local control of 87% and 70%. The dataset represents the clinical situation in a large oncology setting, with many competing treatment options and heterogeneous patient characteristics

Phase III study of iniparib plus gemcitabine and carboplatin versus gemcitabine and carboplatin in patients with metastatic triple-negative breast cancer.

Science.gov (United States)

O'Shaughnessy, Joyce; Schwartzberg, Lee; Danso, Michael A; Miller, Kathy D; Rugo, Hope S; Neubauer, Marcus; Robert, Nicholas; Hellerstedt, Beth; Saleh, Mansoor; Richards, Paul; Specht, Jennifer M; Yardley, Denise A; Carlson, Robert W; Finn, Richard S; Charpentier, Eric; Garcia-Ribas, Ignacio; Winer, Eric P

2014-12-01

There is a lack of treatments providing survival benefit for patients with metastatic triple-negative breast cancer (mTNBC), with no standard of care. A randomized phase II trial showed significant benefit for gemcitabine, carboplatin, and iniparib (GCI) over gemcitabine and carboplatin (GC) in clinical benefit rate, response rate, progression-free survival (PFS), and overall survival (OS). Here, we formally compare the efficacy of these regimens in a phase III trial. Patients with stage IV/locally recurrent TNBC who had received no more than two previous chemotherapy regimens for mTNBC were randomly allocated to gemcitabine 1,000 mg/m(2) and carboplatin area under the curve 2 (days 1 and 8) alone or GC plus iniparib 5.6 mg/kg (days 1, 4, 8, and 11) every 3 weeks. Random assignment was stratified by the number of prior chemotherapies. The coprimary end points were OS and PFS. Patients receiving GC could cross over to iniparib on progression. Five hundred nineteen patients were randomly assigned (261 GCI; 258 GC). In the primary analysis, no statistically significant difference was observed for OS (hazard ratio [HR] = 0.88; 95% CI, 0.69 to 1.12; P = .28) nor PFS (HR = 0.79; 95% CI, 0.65 to 0.98; P = .027). An exploratory analysis showed that patients in the second-/third-line had improved OS (HR = 0.65; 95% CI, 0.46 to 0.91) and PFS (HR = 0.68; 95% CI, 0.50 to 0.92) with GCI. The safety profile for GCI was similar to GC. The trial did not meet the prespecified criteria for the coprimary end points of PFS and OS in the ITT population. The potential benefit with iniparib observed in second-/third-line subgroup warrants further evaluation. © 2014 by American Society of Clinical Oncology.

Angiogenesis-related protein expression in bevacizumab-treated metastatic colorectal cancer: NOTCH1 detrimental to overall survival

International Nuclear Information System (INIS)

Paiva, Tadeu Ferreira Jr.; Jesus, Victor Hugo Fonseca de; Marques, Raul Amorim; Costa, Alexandre André Balieiro Anastácio da; Macedo, Mariana Petaccia de; Peresi, Patricia Maria; Damascena, Aline; Rossi, Benedito Mauro; Begnami, Maria Dirlei; Lima, Vladmir Cláudio Cordeiro de

2015-01-01

The development of targeted therapies has undoubtedly broadened therapeutic options for patients with colorectal cancer (CRC). The use of bevacizumab to reduce angiogenesis has been associated with improved clinical outcomes. However, an urgent need for prognostic/predictive biomarkers for anti-angiogenic therapies still exists. Clinical data of 105 CRC patients treated with bevacizumab in conjunction with chemotherapy were analyzed. The expression of vascular endothelial growth factor (VEGF) receptors, NOTCH1 receptor and its ligand DLL4 were determined by immunohistochemistry. Tumor samples were arranged on a tissue microarray. The association between protein expression and clinicopathological characteristics and outcomes was determined. Bevacizumab was administered as a first-line of treatment in 70.5 % of our cases. The median progression-free survival (PFS) was 10.2 months. The median overall survival (OS) of the total cohort was 24.4 months. Bevacizumab, as the first-line of treatment, and the presence of liver metastasis were independently associated with objective response rate. Membrane VEGFR1 and VEGFR3 expressions were associated with the presence of lung metastasis; interestingly, VEGFR3 was associated with less liver metastasis. NOTCH1 expression was associated with lymph node metastasis. There was a trend toward association between improved PFS and lower NOTCH1 expression (p = 0.06). Improved OS was significantly associated with lower NOTCH1 expression (p = 0.01). In a multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status, liver metastasis, histological grade, and NOTCH1 expression were independently associated with OS. Our findings illustrated the expression profile of angiogenesis-related proteins and their association with clinicopathological characteristics and outcomes. NOTCH1 expression is a detrimental prognostic factor in metastatic CRC patients treated with chemotherapy plus bevacizumab. The online version of

The PREVAIL Study

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Evans, Christopher P; Higano, Celestia S; Keane, Thomas

2016-01-01

BACKGROUND: Enzalutamide, an oral androgen receptor inhibitor, significantly improved overall survival (OS) and radiographic progression-free survival (rPFS) versus placebo in the PREVAIL trial of men with chemotherapy-naïve metastatic castration-resistant prostate cancer. OBJECTIVE: To assess...... in men with chemotherapy-naïve metastatic castration-resistant prostate cancer, with or without visceral disease, low- or high-volume bone disease, or lymph node only disease. PATIENT SUMMARY: Patients with metastatic castration-resistant prostate cancer-including those with or without visceral disease...

Systemic therapy in younger and elderly patients with advanced biliary cancer: sub-analysis of ABC-02 and twelve other prospective trials.

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McNamara, Mairéad Geraldine; Bridgewater, John; Lopes, Andre; Wasan, Harpreet; Malka, David; Jensen, Lars Henrik; Okusaka, Takuji; Knox, Jennifer J; Wagner, Dorothea; Cunningham, David; Shannon, Jenny; Goldstein, David; Moehler, Markus; Bekaii-Saab, Tanios; Valle, Juan W

2017-04-12

Outcomes in younger (ABC) receiving palliative chemotherapy are unclear. This study assessed outcomes in those receiving monotherapy or combination therapy in thirteen prospective systemic-therapy trials. Multivariable analysis explored the impact of therapy on progression-free (PFS) and overall survival (OS) in two separate age cohort groups: ABC, younger patients are rare, and survival in elderly patients in receipt of systemic therapy for advanced disease, whether monotherapy or combination therapy, is similar to that of non-elderly patients, therefore age alone should not influence decisions regarding treatment.

[Early monitoring of BCR-ABL transcript levels and cytogenetic in assessing the prognosis of chronic myeloid leukemia].

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Huang, Qin; Zhang, Xiao-yan; Li, Yan; Wang, Xiao-min

2013-10-15

To explore the prognostic significance of early monitoring of BCR-ABL transcript levels and cytogenetic evaluations for chronic myeloid leukemia in chronic phase (CML-CP). From July 2007 to May 2012, 56 CML-CP patients received oral imatinib 400 mg/d. The BCR-ABL transcript levels were monitored and cytogenetic examinations performed after 3 and 6 months respectively. The median follow-up time was 48 months. The 3-month BCR-ABL transcript levels ≤ 10% of patients 5-year overall survival (OS) and progression-free survival (PFS) were better than BCR-ABL transcript levels >10% of patients (OS: 100% vs 84.6%, P = 0.011; PFS: 94.6% vs 67.7%, P = 0.045); cytogenetics: Ph(+) ≤ 35 % of patients 5-year OS and PFS better than Ph(+) > 35% of patients (OS: 100% vs 76.2%, P = 0.001; PFS: 95.2% vs 38.1%, P = 0.001); the 6-month BCR-ABL transcripts level ≤ 1% of patients 5-year OS and PFS also better than BCR-ABL transcript levels> 1% of patients (OS: 100% vs 71.4%, P = 0.000; PFS: 95.2% vs 47.6%, P = 0.001); Ph(+) = 0% and Ph(+)> 0% patients, 5-year OS and PFS were significantly different (OS: 100% vs 68.6%, P = 0.000; PFS: 95.3% vs 45.7%, P = 0.000). Early molecular biology and cytogenetics monitoring have some significance in the prognostic assessment of CML-CP. And individualized treatment strategies should be based upon the monitoring results in conjunctions with comprehensive judgments.

Joint Serum Tumor Markers Serve as survival predictive model of Erlotinib in the treatment of recurrent Non-small Cell Lung Cancer

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Lan SHAO

2014-05-01

Full Text Available Background and objective Molecular targeting therapy is the direction of individualized treatment of lung cancer, scholars has been established targeted therapy prediction models which provide more guidance for clinical individual therapy. This study investigated the relationship among pulmonary surfactant-associated protein D (SP-D, transforming growth factor α (TGF-α, matrix metalloproteinase 9 (MMP-9, tissue polypeptide specific antigen (TPS, and Krebs von den Lungen-6 (KL-6 and response as well as survival in the patients with recurrent non-small cell lung cancer, which Erlotinib was as second line treatment after failure to chemotherapy. This study also established a predictive prognostic model. Methods Serum levels of SP-D, TGF-α, MMP-9, TPS, and KL-6 in 114 patients before erlotinib treatment were detected by ELISA method. Combined with clinical factors, these levels were used to investigate the relationship with efficacy in erlotinib treatment and construct a predicted prognostic model by Kaplan-Meier curve and Cox proportional hazard model multivariate analysis. Results The objective response rate (ORR and disease control rate (DCR in the 114 patients, were 22.8% (26/114 and 72.8% (83/114, to Erlotinib treatment respectively. The median progression-free survival (PFS and one year survival rate with Erlotinib treatment were 5.13 months and 69.3%, respectively. Patients in the SP-D>110 ng/mL group exhibited more ORR (33.3% vs 13.3%, P=0.011 and DCR (83.3% vs 63.3%, P=0.017 than those in the ≤110 ng/mL group. Patients in the MMP-9≤535 ng/mL group showed more DCR (83.9% than those in the >535 ng/mL group (62.1% (P=0.009. Patients in the TPS110 ng/mL (5.95 months vs 3.25 months, P=0.009, MMP-9≤535 ng/mL (5.83 months vs 3.47 months, P=0.046, KL-6<500 U/mL (6.03 months vs 3.40 months, P=0.040, and TPS<80 U/L (6.15 months vs 2.42 months, P=0.014 groups showed better PFS. Multivariate analysis showed that current or ever-smoker, wild

Impact of high-dose chemotherapy and autologous transplantation as first-line therapy on the survival of high-risk diffuse large B cell lymphoma patients: a single-center study in Japan.

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Inano, Shojiro; Iwasaki, Makoto; Iwamoto, Yoshihiro; Sueki, Yuki; Fukunaga, Akiko; Yanagita, Soshi; Arima, Nobuyoshi

2014-02-01

High-dose chemotherapy (HDT), together with autologous stem cell transplantation (ASCT), plays an important role in the treatment of diffuse large B cell lymphoma (DLBCL), especially as second-line therapy. However, its significance in up-front settings remains to be elucidated. In our institute, patients with DLBCL in both the high-intermediate and high international prognostic index (IPI) groups initially underwent CHOP/R-CHOP treatment followed by HDT/ASCT at upfront settings between 2002 and 2011. We retrospectively analyzed 25 patients who were all treated with upfront HDT/ASCT. We excluded one patient who failed to undergo transplantation because of primary refractory disease from the analysis. The median follow-up was 77 months (range 17-110 months). Five-year overall survival (OS) and progression-free survival (PFS) were 91.7 and 79.2 %, respectively, which were higher than the equivalents in previous studies. The OS and PFS in the high-risk group were lower than those in the high-intermediate group. Treatment-related mortalities or fatal complication were not observed. Our results confirm that HDT/ASCT for high-risk aggressive lymphoma is a feasible and promising therapy, but patients with high IPI continued to have poor prognoses; improvements in treatment strategy are clearly needed. Since HDT/ASCT is an aggressive treatment option associated with long-term complications, we need to identify patient groups that will gain the maximum benefit from HDT/ASCT in the upfront setting.

Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma

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McSweeney, E.N.; Tobias, J.S.; Goldstone, A.H.; Richards, J.D.M. (University Coll. Hospital, London (United Kingdom)); Blackman, G. (Middlesex Hospital, London (United Kingdom))

1993-01-01

Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemo-resistant to initial therapy. Fifteen patients received [alpha]IFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. [alpha]IFN did not appear to prolong survival (OS or PFS) post-DHBI. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy. Cytopenia was a significant problem post-DHBI, such that the role of maintenance [alpha]IFN therapy could not be fully evaluated. (author).

Double hemibody irradiation (DHBI) in the management of relapsed and primary chemoresistant multiple myeloma

International Nuclear Information System (INIS)

McSweeney, E.N.; Tobias, J.S.; Goldstone, A.H.; Richards, J.D.M.; Blackman, G.

1993-01-01

Fifty-five patients with multiple myeloma were treated with both upper and lower hemibody irradiation between January 1985 and January 1991; 42 had relapsed post-plateau and 13 were chemo-resistant to initial therapy. Fifteen patients received αIFN-2b maintenance therapy post-DHBI, at a dose of 3 Mu three times per week. Ninety-five per cent of patients experienced symptomatic improvement in bone pain post-DHBI, 21% of whom discontinued opiate analgesics altogether; 63% had a minor biochemical response and 38% had a partial biochemical response. The overall survival (OS) and progression free survivals (PFS) in all patients were 11 months and 8 months respectively. No significant difference was noted in either OS or PFS, according to whether patients were chemoresistant or had relapsed post-plateau. αIFN did not appear to prolong survival (OS or PFS) post-DHBI. We conclude that DHBI is an effective treatment in patients with relapsed multiple myeloma and in those who are chemoresistant to initial therapy. Cytopenia was a significant problem post-DHBI, such that the role of maintenance αIFN therapy could not be fully evaluated. (author)

Efficacy of Gefitinib for Young Patients with Unknown EGFR Gene Mutation 
in Advanced Lung Adenocarcinoma

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Yutao LIU

2014-05-01

Full Text Available Background and objective Lung cancer in young patients (less or equal to 45 years is relatively rare. We explored the efficacy and survival of Gefitinib for young patients with unknown epidermal growth factor receptor (EGFR gene mutation of advanced lung adenocarcinoma. Methods The clinical data of 55 young patients with unknown EGFR gene mutation in advanced lung adenocarcinoma referred to the Cancer Hospital & Institute, Chinese Academy of Medical Sciences from Jan 2006 through Dec 2010 were analyzed retrospectively. Results Of 55 young patients enrolled, the median age was 41 years. The objective response rate and disease control rate were 43.6% and 90.9%, respectively.. The median progression-free survival (PFS was 9.0 months. Among the factors analyzed, brain metastasis had significant effect on PFS (P=0.017. The median overall survival (OS was 24.0 months. The independent prognostic factors to significantly improve OS included non-smoking history (P=0.028 and receiving other anti-cancer treatment after Gefitinib therapy (P<0.001. Conclusion The median PFS and OS of the young patients with Unknown EGFR gene mutation in advanced lung adenocarcinoma were similar with general population.

Expression of connective tissue growth factor and interleukin-11 in intratumoral tissue is associated with poor survival after curative resection of hepatocellular carcinoma.

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Xiang, Zuo-Lin; Zeng, Zhao-Chong; Fan, Jia; Tang, Zhao-You; Zeng, Hai-Ying

2012-05-01

In the present study, we evaluated the prognostic value of intratumoral and peritumoral expression of connective tissue growth factor (CTGF), transforming growth factor-beta 1 (TGF-β1), and interleukin-11 (IL-11) in patients with hepatocellular carcinoma (HCC) after curative resection. Expression of CTGF, TGF-β1, and IL-11 was assessed by immunohistochemical staining of tissue microarrays containing paired tumor and peritumoral liver tissue from 290 patients who had undergone hepatectomy for histologically proven HCC. The prognostic value of these and other clinicopathologic factors were evaluated. The median follow-up time was 54.3 months (range, 4.3-118.3 months). High intratumoral CTGF expression was associated with vascular invasion (P = 0.015), intratumoral IL-11 expression correlated with higher tumor node metastasis (TNM) stage (P = 0.009), and peritumoral CTGF overexpression correlated with lack of tumor encapsulation (P = 0.031). Correlation analysis of these proteins revealed that intratumoral CTGF and IL-11 correlated with high intratumoral TGF-β1 expression (r = 0.325, P < 0.001; and r = 0.273, P < 0.001, respectively). TNM stage (P < 0.001), high intratumoral CTGF levels (P = 0.010), and intratumoral IL-11 expression (P = 0.015) were independent prognostic factors for progression-free survival (PFS). Vascular invasion (P = 0.032), TNM stage (P < 0.001), high intratumoral CTGF levels (P = 0.036), and intratumoral IL-11 expression (P = 0.013) were independent prognostic factors for overall survival (OS). High intratumoral CTGF and intratumoral IL-11 expression were associated with PFS and OS after hepatectomy, and the combination of intratumoral CTGF with IL-11 may be predictive of survival.

Five-Year Follow-Up of Concomitant Accelerated Hypofractionated Radiation in Advanced Squamous Cell Carcinoma of the Buccal Mucosa: A Retrospective Cohort Study

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Hassan Iqbal

2015-01-01

Full Text Available In resource limited settings, induction chemotherapy with Gemcitabine and Cisplatinum and concurrent hypofractionated chemoradiation for locally advanced carcinoma of buccal mucosa (BMSCC are a cost effective option but remain under reported. The objective of this study was to report long term survival outcome after concurrent hypofractionated radiotherapy in locally advanced BMSCC. Between February 2005 and 2009, 63 patients received treatment. Induction chemotherapy (IC regimen consisted of two drugs: Gemcitabine and Cisplatin. All patients received 55 Gy of radiation in 20 fractions with concurrent single agent Cisplatin (75 mg/m2. Five-year overall survival (OS, disease-free survival (DFS, and progression-free survival (PFS were determined. Based on AJCC staging, 7 (11% patients were stage III, 31 (49% stage IV a, and 25 (40% stage IVb at presentation. After IC, 8 (18% patients had complete radiological response, 33 (73% had partial response, and 4 (9% had stable disease. After concurrent hypofractionated chemoradiation, thirty-nine (62% patients were complete responders and 24 (38% had stable disease. With a minimum follow-up of 60 months, 5-year OS, DFS, and PFS were 30%, 49%, and 30%, respectively. In locally advanced buccal mucosa squamous cell carcinoma, concurrent hypofractionated chemoradiation results in acceptable survival and regimen related toxicity.

Nuclear NF-κB Expression Correlates With Outcome Among Patients With Head and Neck Squamous Cell Carcinoma Treated With Primary Chemoradiation Therapy

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Balermpas, Panagiotis [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Michel, Yvonne [Senckenberg Institute of Pathology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Wagenblast, Jens [Department of Otorhinolaryngology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Seitz, Oliver [Department of Maxillofacial Surgery, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Sipek, Florian; Rödel, Franz; Rödel, Claus [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany); Fokas, Emmanouil, E-mail: emmanouil.fokas@kgu.de [Department of Radiation Therapy and Oncology, J. W. Goethe – University Frankfurt am Main, Frankfurt (Germany)

2013-07-15

Background: To examine whether nuclear NF-κB expression correlates with outcome in patients with head and neck squamous cell carcinoma (HNSCC) treated with primary chemoradiation therapy (CRT). Methods and Materials: Between 2007 and 2010, 101 patients with locally advanced primary HNSCC were treated with definitive simultaneous CRT. Pretreatment biopsy specimens were analyzed for NF-κB p65 (RelA) nuclear immunoreactivity. A sample was assigned to be positive with more than 5% positive nuclear expression. The predictive relevance of NF-κB and clinicopathologic factors for overall survival (OS), progression-free survival (PFS), local progression-free survival (LPFS), and metastasis-free survival (DMFS) was examined by univariate and multivariate analysis. Results: No significant differences between the groups were observed with regard to age, sex, total radiation dose, fractionation mode, total chemotherapy applied, T stage or grading. Patients with p65 nuclear positive biopsy specimens showed significantly a higher rate of lymph node metastasis (cN2c or cN3 status, P=.034). Within a mean follow-up time of 25 months (range, 2.33-62.96 months) OS, PFS, and DMFS were significantly poorer in the p65 nuclear positive group (P=.008, P=.027, and P=.008, respectively). These correlations remained significant in multivariate analysis. Conclusion: NF-κB/p65 nuclear expression is associated with increased lymphatic and hematogenous tumor dissemination and decreased survival in HNSCC patients treated with primary CRT. Our results may foster further investigation of a predictive relevance of NF-κB/p65 and its role as a suitable target for a molecular-based targeted therapy in HNSCC cancer.

SLCO1B1 and SLC19A1 gene variants and irinotecan-induced rapid response and survival: a prospective multicenter pharmacogenetics study of metastatic colorectal cancer.

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Liu Huang

Full Text Available Rapid response to chemotherapy in metastatic colorectal cancer (mCRC patients (response within 12 weeks of chemotherapy may increase the chance of complete resection and improved survival. Few molecular markers predict irinotecan-induced rapid response and survival. Single-nucleotide polymorphisms (SNPs in solute carrier genes are reported to correlate with the variable pharmacokinetics of irinotecan and folate in cancer patients. This study aims to evaluate the predictive role of 3 SNPs in mCRC patients treated with irinotecan and fluoropyrimidine-containing regimens.Three SNPs were selected and genotyped in 137 mCRC patients from a Chinese prospective multicenter trial (NCT01282658. The chi-squared test, univariate and multivariable logistic regression model, and receiver operating characteristic analysis were used to evaluate correlations between the genotypes and rapid response. Kaplan-Meier survival analysis and Cox proportional hazard models were used to evaluate the associations between genotypes and survival outcomes. Benjamini and Hochberg False Discovery Rate correction was used in multiple testing.Genotype GA/AA of SNP rs2306283 of the gene SLCO1B1 and genotype GG of SNP rs1051266 of the gene SLC19A1 were associated with a higher rapid response rate (odds ratio [OR] =3.583 and 3.521, 95%CI =1.301-9.871 and 1.271-9.804, p=0.011 and p=0.013, respectively. The response rate was 70% in patients with both genotypes, compared with only 19.7% in the remaining patients (OR = 9.489, 95%CI = 2.191-41.093, Fisher's exact test p=0.002. Their significances were all maintained even after multiple testing (all p c < 0.05. The rs2306283 GA/AA genotype was also an independent prognostic factor of longer progression-free survival (PFS (hazard ratio = 0.402, 95%CI = 0.171-0.945, p=0.037. None of the SNPs predicted overall survival.Polymorphisms of solute carriers' may be useful to predict rapid response to irinotecan plus fluoropyrimidine and PFS in m

Plant food supplement (PFS) market structure in EC Member States, methods and techniques for the assessment of individual PFS intake

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Vargas-Murga, L.; Garcia-Alvarez, A.; Roman-Vinas, B.; Ngo, J.; Ribas-Barba, L.; Berg, van den S.J.P.L.; Williamson, G.; Serra-Majem, L.

2011-01-01

The popularity of herbal products, especially plant food supplements (PFS) and herbal medicine is on the rise in Europe and other parts of the world, with increased use in the general population as well as among specific subgroups encompassing children, women or those suffering from diseases such as

EGFR gene copy number as a prognostic marker in colorectal cancer patients treated with cetuximab or panitumumab: a systematic review and meta analysis.

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Zheng Jiang

Full Text Available The epidermal growth factor receptor (EGFR gene copy number (GCN has been previously demonstrated to correlate with the clinical outcome of colorectal cancer (CRC treated with anti-EGFR monoclonal antibodies (mAbs, although it remains controversial. We conducted a systematic review and meta-analysis to assess EGFR GCN as a potential biomarker of survival for patients with advanced CRC receiving treatment with anti-EGFR mAbs.We systematically identified articles investigating EGFR GCN by fluorescent or chromogenic in situ hybridization or other detection techniques in patients with metastatic CRC treated with panitumumab or cetuximab, (last search: 10 August 2012. Eligible studies had to report on overall survival (OS, progression-free survival (PFS or time-to-progression (TTP, stratified by EGFR GCN. Summary hazard ratios (HRs were calculated using random-effects models.Among 13 identified studies, 10 (776 patients, 302 with increased GCN, 8 (893 patients, 282 with increased GCN and 3 (149 patients, 66 with increased GCN were eligible for the OS, PFS and TTP meta-analyses, respectively. Increased EGFR GCN was associated with increased OS (HR = 0.62; 95% CI 0.50-0.77; P<0.001, PFS (HR = 0.65; 95% CI 0.47-0.89; P = 0.008 but not TTP (HR = 0.71; 95% CI 0.44-1.14; P = 0.157. It was also shown that EGFR GCN is independent of other factors such as KRAS status. Among those populations received second-line or higher treatment, increased EGFR GCN was strongly associated with improved survival (for OS, HR = 0.60; 95% CI 0.47-0.75; P<0.001; for PFS, HR = 0.59; 95% CI 0.47-0.75; P<0.001, whereas it did not influence survival in patients that received first-line therapy.Among the anti-EGFR-treated patients, increased EGFR GCN appears to be associated with improved survival outcomes. The effect on survival appears to be related to patients receiving the line of treatment.

A viral vectored prime-boost immunization regime targeting the malaria Pfs25 antigen induces transmission-blocking activity.

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Anna L Goodman

Full Text Available The ookinete surface protein Pfs25 is a macrogamete-to-ookinete/ookinete stage antigen of Plasmodium falciparum, capable of exerting high-level anti-malarial transmission-blocking activity following immunization with recombinant protein-in-adjuvant formulations. Here, this antigen was expressed in recombinant chimpanzee adenovirus 63 (ChAd63, human adenovirus serotype 5 (AdHu5 and modified vaccinia virus Ankara (MVA viral vectored vaccines. Two immunizations were administered to mice in a heterologous prime-boost regime. Immunization of mice with AdHu5 Pfs25 at week 0 and MVA Pfs25 at week 10 (Ad-MVA Pfs25 resulted in high anti-Pfs25 IgG titers, consisting of predominantly isotypes IgG1 and IgG2a. A single priming immunization with ChAd63 Pfs25 was as effective as AdHu5 Pfs25 with respect to ELISA titers at 8 weeks post-immunization. Sera from Ad-MVA Pfs25 immunized mice inhibited the transmission of P. falciparum to the mosquito both ex vivo and in vivo. In a standard membrane-feeding assay using NF54 strain P. falciparum, oocyst intensity in Anopheles stephensi mosquitoes was significantly reduced in an IgG concentration-dependent manner when compared to control feeds (96% reduction of intensity, 78% reduction in prevalence at a 1 in 5 dilution of sera. In addition, an in vivo transmission-blocking effect was also demonstrated by direct feeding of immunized mice infected with Pfs25DR3, a chimeric P. berghei line expressing Pfs25 in place of endogenous Pbs25. In this assay the density of Pfs25DR3 oocysts was significantly reduced when mosquitoes were fed on vaccinated as compared to control mice (67% reduction of intensity, 28% reduction in prevalence and specific IgG titer correlated with efficacy. These data confirm the utility of the adenovirus-MVA vaccine platform for the induction of antibodies with transmission-blocking activity, and support the continued development of this alternative approach to transmission-blocking malaria subunit

A gene expression predictor of response to EGFR-targeted therapy stratifies progression-free survival to cetuximab in KRAS wild-type metastatic colorectal cancer

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Black Esther P

2009-05-01

Full Text Available Abstract Background The anti-EGFR monoclonal antibody cetuximab is used in metastatic colorectal cancer (CRC, and predicting responsive patients garners great interest, due to the high cost of therapy. Mutations in the KRAS gene occur in ~40% of CRC and are a negative predictor of response to cetuximab. However, many KRAS-wildtype patients do not benefit from cetuximab. We previously published a gene expression predictor of sensitivity to erlotinib, an EGFR inhibitor. The purpose of this study was to determine if this predictor could identify KRAS-wildtype CRC patients who will benefit from cetuximab therapy. Methods Microarray data from 80 metastatic CRC patients subsequently treated with cetuximab were extracted from the study by Khambata-Ford et al. The study included KRAS status, response, and PFS for each patient. The gene expression data were scaled and analyzed using our predictive model. An improved predictive model of response was identified by removing features in the 180-gene predictor that introduced noise. Results Forty-three of eighty patients were identified as harboring wildtype-KRAS. When the model was applied to these patients, the predicted-sensitive group had significantly longer PFS than the predicted-resistant group (median 88 days vs. 56 days; mean 117 days vs. 63 days, respectively, p = 0.008. Kaplan-Meier curves were also significantly improved in the predicted-sensitive group (p = 0.0059, HR = 0.4109. The model was simplified to 26 of the original 180 genes and this further improved stratification of PFS (median 147 days vs. 56.5 days in the predicted sensitive and resistant groups, respectively, p Conclusion Our model of sensitivity to EGFR inhibition stratified PFS following cetuximab in KRAS-wildtype CRC patients. This study represents the first true external validation of a molecular predictor of response to cetuximab in KRAS-WT metastatic CRC. Our model may hold clinical utility for identifying patients responsive

Biomarker analyses and final overall survival results from a phase III, randomized, open-label, first-line study of gefitinib versus carboplatin/paclitaxel in clinically selected patients with advanced non-small-cell lung cancer in Asia (IPASS).

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Fukuoka, Masahiro; Wu, Yi-Long; Thongprasert, Sumitra; Sunpaweravong, Patrapim; Leong, Swan-Swan; Sriuranpong, Virote; Chao, Tsu-Yi; Nakagawa, Kazuhiko; Chu, Da-Tong; Saijo, Nagahiro; Duffield, Emma L; Rukazenkov, Yuri; Speake, Georgina; Jiang, Haiyi; Armour, Alison A; To, Ka-Fai; Yang, James Chih-Hsin; Mok, Tony S K

2011-07-20

The results of the Iressa Pan-Asia Study (IPASS), which compared gefitinib and carboplatin/paclitaxel in previously untreated never-smokers and light ex-smokers with advanced pulmonary adenocarcinoma were published previously. This report presents overall survival (OS) and efficacy according to epidermal growth factor receptor (EGFR) biomarker status. In all, 1,217 patients were randomly assigned. Biomarkers analyzed were EGFR mutation (amplification mutation refractory system; 437 patients evaluable), EGFR gene copy number (fluorescent in situ hybridization; 406 patients evaluable), and EGFR protein expression (immunohistochemistry; 365 patients evaluable). OS analysis was performed at 78% maturity. A Cox proportional hazards model was used to assess biomarker status by randomly assigned treatment interactions for progression-free survival (PFS) and OS. OS (954 deaths) was similar for gefitinib and carboplatin/paclitaxel with no significant difference between treatments overall (hazard ratio [HR], 0.90; 95% CI, 0.79 to 1.02; P = .109) or in EGFR mutation-positive (HR, 1.00; 95% CI, 0.76 to 1.33; P = .990) or EGFR mutation-negative (HR, 1.18; 95% CI, 0.86 to 1.63; P = .309; treatment by EGFR mutation interaction P = .480) subgroups. A high proportion (64.3%) of EGFR mutation-positive patients randomly assigned to carboplatin/paclitaxel received subsequent EGFR tyrosine kinase inhibitors. PFS was significantly longer with gefitinib for patients whose tumors had both high EGFR gene copy number and EGFR mutation (HR, 0.48; 95% CI, 0.34 to 0.67) but significantly shorter when high EGFR gene copy number was not accompanied by EGFR mutation (HR, 3.85; 95% CI, 2.09 to 7.09). EGFR mutations are the strongest predictive biomarker for PFS and tumor response to first-line gefitinib versus carboplatin/paclitaxel. The predictive value of EGFR gene copy number was driven by coexisting EGFR mutation (post hoc analysis). Treatment-related differences observed for PFS in the EGFR

PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy-Safety and Efficacy in Asian Patients.

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Iwata, Hiroji; Im, Seock-Ah; Masuda, Norikazu; Im, Young-Hyuck; Inoue, Kenichi; Rai, Yoshiaki; Nakamura, Rikiya; Kim, Jee Hyun; Hoffman, Justin T; Zhang, Ke; Giorgetti, Carla; Iyer, Shrividya; Schnell, Patrick T; Bartlett, Cynthia Huang; Ro, Jungsil

2017-08-01

To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy-resistant metastatic breast cancer. The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3) trial, a double-blind phase III study, included 521 patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs) were assessed on study treatment and at the end of treatment. This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71) or placebo plus fulvestrant (n = 31). Palbociclib plus fulvestrant improved progression-free survival (PFS) compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached) but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065). The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92%) and leukopenia (29%); febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.

Antiangiogenic agents in the treatment of recurrent or newly diagnosed glioblastoma: Analysis of single-agent and combined modality approaches

International Nuclear Information System (INIS)

Beal, Kathryn; Abrey, Lauren E; Gutin, Philip H

2011-01-01

Surgical resection followed by radiotherapy and temozolomide in newly diagnosed glioblastoma can prolong survival, but it is not curative. For patients with disease progression after frontline therapy, there is no standard of care, although further surgery, chemotherapy, and radiotherapy may be used. Antiangiogenic therapies may be appropriate for treating glioblastomas because angiogenesis is critical to tumor growth. In a large, noncomparative phase II trial, bevacizumab was evaluated alone and with irinotecan in patients with recurrent glioblastoma; combination treatment was associated with an estimated 6-month progression-free survival (PFS) rate of 50.3%, a median overall survival of 8.9 months, and a response rate of 37.8%. Single-agent bevacizumab also exceeded the predetermined threshold of activity for salvage chemotherapy (6-month PFS rate, 15%), achieving a 6-month PFS rate of 42.6% (p < 0.0001). On the basis of these results and those from another phase II trial, the US Food and Drug Administration granted accelerated approval of single-agent bevacizumab for the treatment of glioblastoma that has progressed following prior therapy. Potential antiangiogenic agents-such as cilengitide and XL184-also show evidence of single-agent activity in recurrent glioblastoma. Moreover, the use of antiangiogenic agents with radiation at disease progression may improve the therapeutic ratio of single-modality approaches. Overall, these agents appear to be well tolerated, with adverse event profiles similar to those reported in studies of other solid tumors. Further research is needed to determine the role of antiangiogenic therapy in frontline treatment and to identify the optimal schedule and partnering agents for use in combination therapy

Prognostic value of whole-body metabolic tumour volume and total lesion glycolysis measured on {sup 18}F-FDG PET/CT in patients with extranodal NK/T-cell lymphoma

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Kim, Choon-Young; Hong, Chae Moon; Kim, Do-Hoon; Son, Seung Hyun; Jeong, Shin Young; Lee, Sang-Woo; Lee, Jaetae; Ahn, Byeong-Cheol [Kyungpook National University School of Medicine and Hospital, Department of Nuclear Medicine, Daegu (Korea, Republic of)

2013-09-15

The aim of this study was to determine whether maximum standardized uptake value (SUVmax), whole-body metabolic tumour volume (WBMTV), and whole-body total lesion glycolysis (WBTLG) measured on pretreatment {sup 18}F-FDG PET/CT can predict prognosis in patients with extranodal natural killer/T-cell lymphoma (ENKTL). We conducted a retrospective analysis of 20 patients with newly-diagnosed ENKTL who underwent pretreatment {sup 18}F-FDG PET/CT. WBMTV and WBTLG were measured automatically using the boundaries of voxels presenting SUV > 3.0. Uni- and multivariate analyses for survival and disease progression were performed using clinical variables and PET parameters (SUVmax, WBMTV, and WBTLG). During the follow-up period (median 26.3 months), 12 patients showed disease progression and 10 patients died from the disease. Receiver operating characteristic curve analysis showed cut-off values for SUVmax, WBMTV and WBTLG of 8.1, 14.4 cm{sup 3} and 52.7, respectively. Univariate analysis showed that the International Prognostic Index (IPI) score and PET parameters were significant predictors of overall survival (OS) and progression-free survival (PFS). Multivariate analysis, even after adjustment for the IPI score, showed that high WBMTV was the best predictor of OS and PFS, and high SUVmax and WBTLG were significant predictors of PFS. Our results suggested that the use of PET parameters together with the IPI score may be useful for detailed prediction of prognosis in ENKTL patients. Therefore, despite a lower IPI score, patients with high PET parameter values might be considered candidates for aggressive therapy to improve clinical outcomes. (orig.)

[Clinical effects for patients with recurrent advanced non-small cell lung cancer treated with icotinib hydrochloride].

Science.gov (United States)

Nong, Jingying; Qin, Na; Wang, Jinghui; Yang, Xinjie; Zhang, Hui; Wu, Yuhua; Lv, Jialin; Zhang, Quan; Zhang, Shucai

2013-05-01

Icotinib hydrochloride is the third single target EGFR-TKI used in clinical treatment of advanced non-small cell lung cancer (NSCLC). Clinical research reports on its efficacy and survival in patients with Recurrent Advanced NSCLC are still little.The aim of this study is to evaluate the efficacy and survival of Icotinib hydrochloride for patients with advanced non-small cell lung cancer who failed to previous chemotherapy and explore the association of clinical features with the efficacy and survival. The clinical data of 60 NSCLC patients referred to the Beijing Chest Hospital, Capital Medical University from March 2009 to July 2012 were retrospectively analyzed. The overall response rate (ORR) was 45.0% and the disease control rate (DCR) was 80.0%. The median progression-free survival (PFS) time was 6.7 months. RR and PFS in female were superior to male (P=0.014, 0.013, respectively). RR, DCR in 2nd-line subgroup were superior to ≥3rd-line subgroup (P=0.020, 0.024, respectively). RR, DCR and PFS in EGFR mutation carriers were significantly superior to wild-type patients (P=0.006, Icotinib hydrochloride is effective especially in EGFR mutation carriers and well tolerated in patients with recurrent advanced non-small-cell lung cancer.

Option A improved HIV-free infant survival and mother to child HIV transmission at 9-18 months in Zimbabwe.

Science.gov (United States)

Buzdugan, Raluca; Kang Dufour, Mi-Suk; McCoy, Sandra I; Watadzaushe, Constancia; Dirawo, Jeffrey; Mushavi, Angela; Mujuru, Hilda Angela; Mahomva, Agnes; Kangwende, Rugare Abigail; Hakobyan, Anna; Mugurungi, Owen; Cowan, Frances M; Padian, Nancy S

2016-06-19

We evaluated the impact of Option A on HIV-free infant survival and mother-to-child transmission (MTCT) in Zimbabwe. Serial cross-sectional community-based serosurveys. We analyzed serosurvey data collected in 2012 and 2014 among mother-infant pairs from catchment areas of 132 health facilities from five of 10 provinces in Zimbabwe. Eligible infants (alive or deceased) were born 9-18 months before each survey to mothers at least 16 years old. We randomly selected mother-infant pairs and conducted questionnaires, verbal autopsies, and collected blood samples. We estimated the HIV-free infant survival and MTCT rate within each catchment area and compared the 2012 and 2014 estimates using a paired t test and number of HIV infections averted because of the intervention. We analyzed 7249 mother-infant pairs with viable maternal specimens collected in 2012 and 8551 in 2014. The mean difference in the catchment area level MTCT between 2014 and 2012 was -5.2 percentage points (95% confidence interval = -8.1, -2.3, P Option A regimen. The association between HIV-free infant survival and duration of Option A implementation was NS at the multivariate level (P = 0.093). We found a substantial and statistically significant increase in HIV-free survival and decrease in MTCT among infants aged 9-18 months following Option A rollout in Zimbabwe. This is the only evaluation of Option A and shows the effectiveness of Option A and Zimbabwe's remarkable progress toward eMTCT.

Antiangiogenic therapy in breast cancer

OpenAIRE

Gampenrieder, Simon Peter; Westphal, Theresa; Greil, Richard

2017-01-01

Summary Based on a strong rationale for anti-VEGF (vascular endothelial growth factor) treatment in breast cancer and promising preclinical data, great hopes have been placed on the anti-VEGF antibody bevacizumab. Clinical trials, however, reported conflicting results. In metastatic human epidermal growth factor receptor 2(HER2)-negative breast cancer, the addition of bevacizumab to standard chemotherapy improved consistently progression-free survival (PFS), however, without effect on overall...

Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.

Science.gov (United States)

Reardon, David A; Egorin, Merrill J; Quinn, Jennifer A; Rich, Jeremy N; Rich, Jeremy N; Gururangan, Sridharan; Gururangan, Idharan; Vredenburgh, James J; Desjardins, Annick; Sathornsumetee, Sith; Provenzale, James M; Herndon, James E; Dowell, Jeannette M; Badruddoja, Michael A; McLendon, Roger E; Lagattuta, Theodore F; Kicielinski, Kimberly P; Dresemann, Gregor; Sampson, John H; Friedman, Allan H; Salvado, August J; Friedman, Henry S

2005-12-20

We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.

Treatment strategy for metastatic prostate cancer with extremely high PSA level: reconsidering the value of vintage therapy.

Science.gov (United States)

Yamada, Yasutaka; Sakamoto, Shinichi; Amiya, Yoshiyasu; Sasaki, Makoto; Shima, Takayuki; Komiya, Akira; Suzuki, Noriyuki; Akakura, Koichiro; Ichikawa, Tomohiko; Nakatsu, Hiroomi

2018-05-04

The prognostic significance of initial prostate-specific antigen (PSA) level for metastatic prostate cancer remains uncertain. We investigated the differences in prognosis and response to hormonal therapies of metastatic prostate cancer patients according to initial PSA levels. We analyzed 184 patients diagnosed with metastatic prostate cancer and divided them into three PSA level groups as follows: low (PSA progression-free survival (PFS) for first-line ADT and overall survival (OS) within each of the three groups. Furthermore, we analyzed response to antiandrogen withdrawal (AW) and alternative antiandrogen (AA) therapies after development of castration-resistant prostate cancer (CRPC). No significant differences in OS were observed among the three groups (P = 0.654). Patients with high PSA levels had significantly short PFS for first-line ADT (P = 0.037). Conversely, patients in the high PSA level group had significantly longer PFS when treated with AW than those in the low PSA level group (P = 0.047). Furthermore, patients with high PSA levels had significantly longer PFS when provided with AA therapy (P = 0.049). PSA responders to AW and AA therapies had significantly longer survival after CRPC development than nonresponders (P = 0.011 and P PSA level predicted favorable response to vintage sequential ADT and AW. The current data suggest a novel aspect of extremely high PSA value as a favorable prognostic marker after development of CRPC.

ERGO: a pilot study of ketogenic diet in recurrent glioblastoma.

Science.gov (United States)

Rieger, Johannes; Bähr, Oliver; Maurer, Gabriele D; Hattingen, Elke; Franz, Kea; Brucker, Daniel; Walenta, Stefan; Kämmerer, Ulrike; Coy, Johannes F; Weller, Michael; Steinbach, Joachim P

2014-06-01

Limiting dietary carbohydrates inhibits glioma growth in preclinical models. Therefore, the ERGO trial (NCT00575146) examined feasibility of a ketogenic diet in 20 patients with recurrent glioblastoma. Patients were put on a low-carbohydrate, ketogenic diet containing plant oils. Feasibility was the primary endpoint, secondary endpoints included the percentage of patients reaching urinary ketosis, progression-free survival (PFS) and overall survival. The effects of a ketogenic diet alone or in combination with bevacizumab was also explored in an orthotopic U87MG glioblastoma model in nude mice. Three patients (15%) discontinued the diet for poor tolerability. No serious adverse events attributed to the diet were observed. Urine ketosis was achieved at least once in 12 of 13 (92%) evaluable patients. One patient achieved a minor response and two patients had stable disease after 6 weeks. Median PFS of all patients was 5 (range, 3-13) weeks, median survival from enrollment was 32 weeks. The trial allowed to continue the diet beyond progression. Six of 7 (86%) patients treated with bevacizumab and diet experienced an objective response, and median PFS on bevacizumab was 20.1 (range, 12-124) weeks, for a PFS at 6 months of 43%. In the mouse glioma model, ketogenic diet alone had no effect on median survival, but increased that of bevacizumab-treated mice from 52 to 58 days (pketogenic diet is feasible and safe but probably has no significant clinical activity when used as single agent in recurrent glioma. Further clinical trials are necessary to clarify whether calorie restriction or the combination with other therapeutic modalities, such as radiotherapy or anti-angiogenic treatments, could enhance the efficacy of the ketogenic diet.

Greater efficacy of chemotherapy plus bevacizumab compared to chemo- and targeted therapy alone on non-small cell lung cancer patients with brain metastasis.

Science.gov (United States)

Tang, Ning; Guo, Jun; Zhang, Qianqian; Wang, Yali; Wang, Zhehai

2016-01-19

Control of non-small-cell lung cancer (NSCLC) with brain metastasis is clinically challenging. This study retrospectively evaluated the efficacy of different adjuvant therapies for 776 cases of advanced NSCLCs with brain metastasis who treated with chemotherapy, chemotherapy plus bevacizumab, tyrosine kinase inhibitor (TKI) alone, or supportive care. The median progression-free survival (mPFS) and median overall survival (mOS) of patients treated with chemotherapy plus bevacizumab were 8.5 and 10.5 months, respectively, which were better than those of patients treated with other three therapies(P chemotherapy plus bevacizumab but was significantly better than that of other therapies. Moreover, for patients with EGFR wild-type NSCLC, the mPFS and mOS after chemotherapy plus bevacizumab were greater than those with other two therapies (P Chemotherapy plus bevacizumab was more effective for NSCLC patients with brain metastasis. Further studies will investigate the benefit of TKI alone for patients with EGFR-mutated. For patients with EGFR wild-type, chemotherapy plus bevacizumab did improve PFS and OS. Furthermore, regimens including pemetrexed led to a greater RR.

Baseline prostate-specific antigen levels following treatment with abiraterone acetate as a prognostic factor in castration-resistant prostate cancer.

Science.gov (United States)

Hiroshige, Tasuku; Eguchi, Yoshiro; Yoshizumi, Osamu; Chikui, Katsuaki; Kumagai, Hisaji; Kawaguchi, Yoshihiro; Onishi, Rei; Hayashi, Tokumasa; Watanabe, Kouta; Mitani, Tomotaro; Saito, Koujiro; Igawa, Tsukasa

2018-05-01

The aim of the present study was to investigate the prognostic factors associated with progression-free survival (PFS) and overall survival (OS) times in patients with castration-resistant prostate cancer (CRPC) who received treatment with abiraterone acetate (AA) in routine clinical settings. A total of 93 patients treated with AA between September 2014 and February 2017 were selected and their medical records were analyzed retrospectively. The median PFS time of docetaxel (DTX)-naïve patients was 171 days, and that of post-DTX patients was 56 days. The OS time of DTX-naïve patients did not reach the median. The median OS time of post-DTX patients was 761 days. Multivariate analyses identified baseline prostate-specific antigen (PSA) level prior to treatment with AA and the PSA response rate as independent prognostic factors for PFS time, and baseline PSA prior to treatment with AA as the only independent prognostic factor for OS time. The results of the present study indicate that the baseline PSA level prior to treatment with AA is a notable prognostic factor in patients with CRPC.

Clinical Effects for Patients with Recurrent Advanced Non-small Cell Lung Cancer Treated with Icotinib Hydrochloride

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Jingying NONG

2013-05-01

Full Text Available Background and objective Icotinib hydrochloride is the third single target EGFR-TKI used in clinical treatment of advanced non-small cell lung cancer (NSCLC. Clinical research reports on its efficacy and survival in patients with Recurrent Advanced NSCLC are still little.The aim of this study is to evaluate the efficacy and survival of Icotinib hydrochloride for patients with advanced non-small cell lung cancer who failed to previous chemotherapy and explore the association of clinical features with the efficacy and survival. Methods The clinical data of 60 NSCLC patients referred to the Beijing Chest Hospital, Capital Medical University from March 2009 to July 2012 were retrospectively analyzed. Results The overall response rate (ORR was 45.0% and the disease control rate (DCR was 80.0%. The median progression-free survival (PFS time was 6.7 months. RR and PFS in female were superior to male (P=0.014, 0.013, respectively. RR, DCR in 2nd-line subgroup were superior to ≥3rd-line subgroup (P=0.020, 0.024, respectively. RR, DCR and PFS in EGFR mutation carriers were significantly superior to wild-type patients (P=0.006, <0.001, 0.002, respectively . There was no statistical difference in RR and PFS between those age <65 and ≥65 or PS<2 and PS≥2. There was no statistical difference in RR and DCR between exon 19 deletion and exon 21 mutations, while the former had much longer PFS (P=0.020. EGFR mutation and exon 19 deletion are the independent prognostic factors to significantly improve the PFS (P=0.009, 0.012, respectively. The side effects were generally mild and consisted of rash and diarrhea. Conclusion Icotinib hydrochloride is effective especially in EGFR mutation carriers and well tolerated in patients with recurrent advanced non-small-cell lung cancer.

20 Gy Versus 44 Gy of Supplemental External Beam Radiotherapy With Palladium-103 for Patients With Greater Risk Disease: Results of a Prospective Randomized Trial

International Nuclear Information System (INIS)

Merrick, Gregory S.; Wallner, Kent E.; Butler, Wayne M.; Galbreath, Robert W.; Taira, Al V.; Orio, Peter; Adamovich, Edward

2012-01-01

Purpose: The necessity of external beam radiotherapy (EBRT) as a supplement to prostate brachytherapy remains unknown. We report brachytherapy outcomes for patients with higher risk features randomized to substantially different supplemental EBRT regimens. Methods and Materials: Between December 1999 and June 2004, 247 patients were randomized to 20 Gy vs. 44 Gy EBRT followed by a palladium-103 boost (115 Gy vs. 90 Gy). The eligibility criteria included clinically organ-confined disease with Gleason score 7–10 and/or pretreatment prostate-specific antigen (PSA) level 10–20 ng/mL. The median follow-up period was 9.0 years. Biochemical progression-free survival (bPFS) was defined as a PSA level of ≤0.40 ng/mL after nadir. The median day 0 prescribed dose covering 90% of the target volume was 125.7%; 80 men received androgen deprivation therapy (median, 4 months). Multiple parameters were evaluated for their effect on bPFS. Results: For the entire cohort, the cause-specific survival, bPFS, and overall survival rates were 97.7%, 93.2%, and 80.8% at 8 years and 96.9%, 93.2%, and 75.4% at 10 years, respectively. The bPFS rate was 93.1% and 93.4% for the 20-Gy and 44-Gy arms, respectively (p = .994). However, no statistically significant differences were found in cause-specific survival or overall survival were identified. When stratified by PSA level of ≤10 ng/mL vs. >10 ng/mL, Gleason score, or androgen deprivation therapy, no statistically significant differences in bPFS were discerned between the two EBRT regimens. On multivariate analysis, bPFS was most closely related to the preimplant PSA and clinical stage. For patients with biochemically controlled disease, the median PSA level was <0.02 ng/mL. Conclusion: The results of the present trial strongly suggest that two markedly different supplemental EBRT regimens result in equivalent cause-specific survival, bPFS, and overall survival. It is probable that the lack of benefit for a higher supplemental EBRT

Genome-wide Analysis Identifies Novel Loci Associated with Ovarian Cancer Outcomes

DEFF Research Database (Denmark)

Johnatty, Sharon E; Tyrer, Jonathan P; Kar, Siddhartha

2015-01-01

PURPOSE: Chemotherapy resistance remains a major challenge in the treatment of ovarian cancer. We hypothesize that germline polymorphisms might be associated with clinical outcome. EXPERIMENTAL DESIGN: We analyzed approximately 2.8 million genotyped and imputed SNPs from the iCOGS experiment...... for progression-free survival (PFS) and overall survival (OS) in 2,901 European epithelial ovarian cancer (EOC) patients who underwent first-line treatment of cytoreductive surgery and chemotherapy regardless of regimen, and in a subset of 1,098 patients treated with ≥ 4 cycles of paclitaxel and carboplatin...... at standard doses. We evaluated the top SNPs in 4,434 EOC patients, including patients from The Cancer Genome Atlas. In addition, we conducted pathway analysis of all intragenic SNPs and tested their association with PFS and OS using gene set enrichment analysis. RESULTS: Five SNPs were significantly...

A randomised, phase II study of repeated rhenium-188-HEDP combined with docetaxel and prednisone versus docetaxel and prednisone alone in castration-resistant prostate cancer (CRPC) metastatic to bone; the Taxium II trial

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Dodewaard-de Jong, Joyce M. van [VU University Medical Centre, Department of Medical Oncology, Amsterdam (Netherlands); Meander Medical Centre, Department of Medical Oncology, Amersfoort (Netherlands); Klerk, John M.H. de [Meander Medical Centre, Department of Nuclear Medicine, Amersfoort (Netherlands); Bloemendal, Haiko J. [Meander Medical Centre, Department of Medical Oncology, Amersfoort (Netherlands); University Medical Centre Utrecht, Department of Medical Oncology, Utrecht (Netherlands); Oprea-Lager, Daniela E.; Hoekstra, Otto S. [VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Berg, H.P. van den [Tergooi Medical Hospital, Department of Medical Oncology, Hilversum (Netherlands); Los, Maartje [St Antonius Hospital Utrecht, Department of Medical Oncology, Utrecht (Netherlands); Beeker, Aart [Spaarne Gasthuis, Department of Medical Oncology, Hoofddorp (Netherlands); Jonker, Marianne A. [VU University Medical Centre, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); O' Sullivan, Joe M. [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast, Northern Ireland (United Kingdom); Verheul, Henk M.W.; Eertwegh, Alfons J.M. van den [VU University Medical Centre, Department of Medical Oncology, Amsterdam (Netherlands)

2017-08-15

Rhenium-188-HEDP is a beta-emitting radiopharmaceutical used for palliation of metastatic bone pain. We investigated whether the addition of rhenium-188-HEDP to docetaxel/prednisone improved efficacy of chemotherapy in patients with CRPC. Patients with progressive CRPC and osteoblastic bone metastases were randomised for first-line docetaxel 75 mg/m{sup 2} 3-weekly plus prednisone with or without 2 injections of rhenium-188-HEDP after the third (40 MBq/kg) and after the sixth (20 MBq/kg) cycle of docetaxel. Primary endpoint was progression-free survival (PFS), defined as either PSA, radiographic or clinical progression. Patients were stratified by extent of bone metastases and hospital. Forty-two patients were randomised for standard treatment and 46 patients for combination therapy. Median number of cycles of docetaxel was 9 in the control group and 8 in the experimental group. Median follow-up was 18.4 months. Two patients from the experimental group did not start treatment after randomisation. In the intention to treat analysis no differences in PFS, survival and PSA became apparent between the two groups. In an exploratory per-protocol analysis median overall survival was significantly longer in the experimental group (33.8 months (95%CI 31.75-35.85)) than in the control group (21.0 months (95%CI 13.61-28.39); p 0.012). Also median PFS in patients with a baseline phosphatase >220U/L was significantly better with combination treatment (9.0 months (95%CI 3.92-14.08) versus 6.2 months (95%CI 3.08-9.32); log rank p 0.005). As expected, thrombocytopenia (grade I/II) was reported more frequently in the experimental group (25% versus 0%). Combined treatment with rhenium-188-HEDP and docetaxel did not prolong PFS in patients with CRPC. The observed survival benefit in the per-protocol analysis warrants further studies in the combined treatment of chemotherapy and radiopharmaceuticals. (orig.)

Outcome of Patients With Metastatic Sarcomatoid Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

DEFF Research Database (Denmark)

Kyriakopoulos, Christos E; Chittoria, Namita; Choueiri, Toni K

2015-01-01

BACKGROUND: Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. PATIENTS AND METHODS: Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology......% intermediate risk, and 40% vs. 24% poor risk; P system metastases (6...... of second- (P = .018) and third-line (P systemic therapy. The median progression-free survival (PFS)/overall survival (OS) was 4.5/10.4 months in sRCC patients and 7.8/22.5 months in non-sRCC patients (P

Characterizing the outcomes of metastatic papillary renal cell carcinoma

DEFF Research Database (Denmark)

Connor Wells, John; Donskov, Frede; Fraccon, Anna P

2017-01-01

Outcomes of metastatic papillary renal cell carcinoma (pRCC) patients are poorly characterized in the era of targeted therapy. A total of 5474 patients with metastatic renal cell carcinoma (mRCC) in the International mRCC Database Consortium (IMDC) were retrospectively analyzed. Outcomes were...... compared between clear cell (ccRCC; n = 5008) and papillary patients (n = 466), and recorded type I and type II papillary patients (n = 30 and n = 165, respectively). Overall survival (OS), progression-free survival (PFS), and overall response rate (ORR) favored ccRCC over pRCC. OS was 8 months longer...

Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases

International Nuclear Information System (INIS)

Gorovets, Daniel; Ayala-Peacock, Diandra; Tybor, David J.; Rava, Paul; Ebner, Daniel; Cielo, Deus; Norén, Georg; Wazer, David E.; Chan, Michael; Hepel, Jaroslaw T.

2017-01-01

Purpose: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS. Methods and Materials: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation. Results: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(−) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62. Conclusions: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.

Multi-institutional Nomogram Predicting Survival Free From Salvage Whole Brain Radiation After Radiosurgery in Patients With Brain Metastases

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Gorovets, Daniel [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Department of Radiation Oncology, Perlmutter Cancer Center, NYU School of Medicine, New York, New York (United States); Ayala-Peacock, Diandra [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee (United States); Tybor, David J. [Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts (United States); Rava, Paul [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Department of Radiation Oncology, UMass Memorial Medical Center, University of Massachusetts School of Medicine, Worcester, Massachusetts (United States); Ebner, Daniel [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Cielo, Deus; Norén, Georg [Department of Neurosurgery, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Wazer, David E. [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States); Chan, Michael [Department of Radiation Oncology, Wake Forest School of Medicine, Winston-Salem, North Carolina (United States); Hepel, Jaroslaw T., E-mail: jhepel@lifespan.org [Department of Radiation Oncology, Rhode Island Hospital, Brown University Warren Alpert Medical School, Providence, Rhode Island (United States)

2017-02-01

Purpose: Optimal patient selection for stereotactic radiosurgery (SRS) as the initial treatment for brain metastases is complicated and controversial. This study aimed to develop a nomogram that predicts survival without salvage whole brain radiation therapy (WBRT) after upfront SRS. Methods and Materials: Multi-institutional data were analyzed from 895 patients with 2095 lesions treated with SRS without prior or planned WBRT. Cox proportional hazards regression model was used to identify independent pre-SRS predictors of WBRT-free survival, which were integrated to build a nomogram that was subjected to bootstrap validation. Results: Median WBRT-free survival was 8 months (range, 0.1-139 months). Significant independent predictors for inferior WBRT-free survival were age (hazard ratio [HR] 1.1 for each 10-year increase), HER2(−) breast cancer (HR 1.6 relative to other histologic features), colorectal cancer (HR 1.4 relative to other histologic features), increasing number of brain metastases (HR 1.09, 1.32, 1.37, and 1.87 for 2, 3, 4, and 5+ lesions, respectively), presence of neurologic symptoms (HR 1.26), progressive systemic disease (HR 1.35), and increasing extracranial disease burden (HR 1.31 for oligometastatic and HR 1.56 for widespread). Additionally, HER2(+) breast cancer (HR 0.81) and melanoma (HR 1.11) trended toward significance. The independently weighted hazard ratios were used to create a nomogram to display estimated probabilities of 6-month and 12-month WBRT-free survival with a corrected Harrell's C concordance statistic of 0.62. Conclusions: Our nomogram can be used at initial evaluation to help select patients best suited for upfront SRS for brain metastases while reducing expense and morbidity in patients who derive minimal or no benefit.

Phase II study of bevacizumab and temsirolimus combination therapy for recurrent glioblastoma multiforme

DEFF Research Database (Denmark)

Lassen, Ulrik; Sorensen, Morten; Gaziel, Tine Bernhardtsen

2013-01-01

standard temozolomide chemoradiotherapy and bevacizumab-containing second-line therapy, received temsirolimus (25 mg i.v.) on days 1 and 8 and bevacizumab (10 mg/kg) on day 8, every two weeks. Assessments were performed every eight weeks. Blood samples for biomarkers were collected weekly for the first...... eight weeks and at progression. The primary end-point was median progression-free survival (PFS) and secondary end-points were radiographic response, overall survival (OS), and safety of the bevacizumab-temsirolimus combination. RESULTS: Thirteen patients were included, whereof three went off....../10), infection (1/10), hypertension (1/10), and hyperglycemia (1/10). CONCLUSION: Temsirolimus can be safely administered in combination with bevacizumab. This study failed to detect activity of such a combination in patients with progressive GBM beyond bevacizumab therapy....

A pooled analysis of sequential therapies with sorafenib and sunitinib in metastatic renal cell carcinoma.

Science.gov (United States)

Stenner, Frank; Chastonay, Rahel; Liewen, Heike; Haile, Sarah R; Cathomas, Richard; Rothermundt, Christian; Siciliano, Raffaele D; Stoll, Susanna; Knuth, Alexander; Buchler, Tomas; Porta, Camillo; Renner, Christoph; Samaras, Panagiotis

2012-01-01

To evaluate the optimal sequence for the receptor tyrosine kinase inhibitors (rTKIs) sorafenib and sunitinib in metastatic renal cell cancer. We performed a retrospective analysis of patients who had received sequential therapy with both rTKIs and integrated these results into a pooled analysis of available data from other publications. Differences in median progression-free survival (PFS) for first- (PFS1) and second-line treatment (PFS2), and for the combined PFS (PFS1 plus PFS2) were examined using weighted linear regression. In the pooled analysis encompassing 853 patients, the median combined PFS for first-line sunitinib and 2nd-line sorafenib (SuSo) was 12.1 months compared with 15.4 months for the reverse sequence (SoSu; 95% CI for difference 1.45-5.12, p = 0.0013). Regarding first-line treatment, no significant difference in PFS1 was noted regardless of which drug was initially used (0.62 months average increase on sorafenib, 95% CI for difference -1.01 to 2.26, p = 0.43). In second-line treatment, sunitinib showed a significantly longer PFS2 than sorafenib (average increase 2.66 months, 95% CI 1.02-4.3, p = 0.003). The SoSu sequence translates into a longer combined PFS compared to the SuSo sequence. Predominantly the superiority of sunitinib regarding PFS2 contributed to the longer combined PFS in sequential use. Copyright © 2012 S. Karger AG, Basel.

Co-expression of CD147 and GLUT-1 indicates radiation resistance and poor prognosis in cervical squamous cell carcinoma.

Science.gov (United States)

Huang, Xin-Qiong; Chen, Xiang; Xie, Xiao-Xue; Zhou, Qin; Li, Kai; Li, Shan; Shen, Liang-Fang; Su, Juan

2014-01-01

The aim of this study was to investigate the association of CD147 and GLUT-1, which play important roles in glycolysis in response to radiotherapy and clinical outcomes in patients with locally advanced cervical squamous cell carcinoma (LACSCC). The records of 132 female patients who received primary radiation therapy to treat LACSCC at FIGO stages IB-IVA were retrospectively reviewed. Forty-seven patients with PFS (progression-free survival) of less than 36 months were regarded as radiation-resistant. Eighty-five patients with PFS longer than 36 months were regarded as radiation-sensitive. Using pretreatment paraffin-embedded tissues, we evaluated CD147 and GLUT-1 expression by immunohistochemistry. Overexpression of CD147, GLUT-1, and CD147 and GLUT-1 combined were 44.7%, 52.9% and 36.5%, respectively, in the radiation-sensitive group, and 91.5%, 89.4% and 83.0%, respectively, in the radiation-resistant group. The 5-year progress free survival (PFS) rates in the CD147-low, CD147-high, GLUT-1-low, GLUT-1-high, CD147- and/or GLUT-1-low and CD147- and GLUT-1- dual high expression groups were 66.79%, 87.10%, 52.78%, 85.82%, 55.94%, 82.90% and 50.82%, respectively. CD147 and GLUT-1 co-expression, FIGO stage and tumor diameter were independent poor prognostic factors for patients with LACSCC in multivariate Cox regression analysis. Patients with high expression of CD147 alone, GLUT-1 alone or co-expression of CD147 and GLUT-1 showed greater resistance to radiotherapy and a shorter PFS than those with low expression. In particular, co-expression of CD147 and GLUT-1 can be considered as a negative independent prognostic factor.

Outcomes in 370 patients with mantle cell lymphoma treated with ibrutinib: a pooled analysis from three open-label studies.

Science.gov (United States)

Rule, Simon; Dreyling, Martin; Goy, Andre; Hess, Georg; Auer, Rebecca; Kahl, Brad; Cavazos, Nora; Liu, Black; Yang, Shiyi; Clow, Fong; Goldberg, Jenna D; Beaupre, Darrin; Vermeulen, Jessica; Wildgust, Mark; Wang, Michael

2017-11-01

Ibrutinib is highly active in treating mantle cell lymphoma (MCL), an aggressive B-cell lymphoma. We pooled data from three ibrutinib studies to explore the impact of baseline patient characteristics on treatment response. Patients with relapsed/refractory MCL (n = 370) treated with ibrutinib had an objective response rate (ORR) of 66% (20% complete response; 46% partial response); median duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were 18·6, 12·8 and 25·0 months, respectively. Univariate analyses showed patients with one versus >one prior line of therapy had longer OS. Multivariate analyses identified that one prior line of therapy affected PFS; Eastern Cooperative Oncology Group (ECOG) performance status, simplified MCL international prognostic index (sMIPI) score, bulky disease, and blastoid histology affected OS and PFS. Patients with blastoid versus non-blastoid histology had similar time to best response, but lower ORR, DOR, PFS and OS. OS and PFS were longer in patients with better sMIPI, patients with ECOG performance status 0-1, non-bulky disease and non-blastoid histology. Additionally, the proportion of patients with poor prognostic factors increased with increasing lines of therapy. Together, results suggest that patient outcomes following treatment failure with ibrutinib are related to the natural biological evolution of the disease. © 2017 John Wiley & Sons Ltd.

The prognostic value of FET PET at radiotherapy planning in newly diagnosed glioblastoma

Energy Technology Data Exchange (ETDEWEB)

Hoejklint Poulsen, Sidsel [The Finsen Center, Rigshospitalet, Department of Radiation Biology, Copenhagen (Denmark); Center of Diagnostic Investigation, Rigshospitalet, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen (Denmark); Urup, Thomas; Grunnet, Kirsten; Skovgaard Poulsen, Hans [The Finsen Center, Rigshospitalet, Department of Radiation Biology, Copenhagen (Denmark); The Finsen Center, Rigshospitalet, Department of Oncology, Copenhagen (Denmark); Jarle Christensen, Ib [University of Copenhagen, Hvidovre Hospital, Laboratory of Gastroenterology, Copenhagen (Denmark); Larsen, Vibeke Andree [Center of Diagnostic Investigation, Rigshospitalet, Department of Radiology, Copenhagen (Denmark); Lundemann Jensen, Michael; Munck af Rosenschoeld, Per [The Finsen Center, Rigshospitalet, Department of Oncology, Copenhagen (Denmark); The Finsen Center, Rigshospitalet, Section of Radiotherapy, Copenhagen (Denmark); Law, Ian [Center of Diagnostic Investigation, Rigshospitalet, Department of Clinical Physiology, Nuclear Medicine and PET, Copenhagen (Denmark)

2017-03-15

Glioblastoma patients show a great variability in progression free survival (PFS) and overall survival (OS). To gain additional pretherapeutic information, we explored the potential of O-(2-{sup 18}F-fluoroethyl)-L-tyrosine (FET) PET as an independent prognostic biomarker. We retrospectively analyzed 146 consecutively treated, newly diagnosed glioblastoma patients. All patients were treated with temozolomide and radiation therapy (RT). CT/MR and FET PET scans were obtained postoperatively for RT planning. We used Cox proportional hazards models with OS and PFS as endpoints, to test the prognostic value of FET PET biological tumor volume (BTV). Median follow-up time was 14 months, and median OS and PFS were 16.5 and 6.5 months, respectively. In the multivariate analysis, increasing BTV (HR = 1.17, P < 0.001), poor performance status (HR = 2.35, P < 0.001), O(6)-methylguanine-DNA methyltransferase protein status (HR = 1.61, P = 0.024) and higher age (HR = 1.32, P = 0.013) were independent prognostic factors of poor OS. For poor PFS, only increasing BTV (HR = 1.18; P = 0.002) was prognostic. A prognostic index for OS was created based on the identified prognostic factors. Large BTV on FET PET is an independent prognostic factor of poor OS and PFS in glioblastoma patients. With the introduction of FET PET, we obtain a prognostic index that can help in glioblastoma treatment planning. (orig.)

Efficacy and safety of bevacizumab plus chemotherapy compared to chemotherapy alone in previously untreated advanced or metastatic colorectal cancer: a systematic review and meta-analysis

International Nuclear Information System (INIS)

Botrel, Tobias Engel Ayer; Clark, Luciana Gontijo de Oliveira; Paladini, Luciano; Clark, Otávio Augusto C.

2016-01-01

Colorectal cancer (CRC) is the fourth most frequently diagnosed cancer and the second leading cause of neoplasm-related death in the United States. Several studies analyzed the efficacy of bevacizumab combined with different chemotherapy regimens consisting on drugs such as 5-FU, capecitabine, irinotecan and oxaliplatin. This systematic review aims to evaluate the effectiveness and safety of chemotherapy plus bevacizumab versus chemotherapy alone in patients with previously untreated advanced or metastatic colorectal cancer (mCRC). Several databases were searched, including MEDLINE, EMBASE, LILACS, and CENTRAL. The primary endpoints were overall survival and progression-free survival. Data extracted from the studies were combined by using hazard ratio (HR) or risk ratio (RR) with their corresponding 95 % confidence intervals (95 % CI). The final analysis included 9 trials comprising 3,914 patients. Patients who received the combined treatment (chemotherapy + bevacizumab) had higher response rates (RR = 0.89; 95 % CI: 0.82 to 0.96; p = 0.003) with heterogeneity, higher progression-free survival (HR = 0.69; 95 % CI: 0.63 to 0.75; p < 0.00001) and also higher overall survival rates (HR = 0.87; 95 % CI: 0.80 to 0.95; p = 0.002) with moderate heterogeneity. Regarding adverse events and severe toxicities (grade ≥ 3), the group receiving the combined therapy had higher rates of hypertension (RR = 3.56 95 % CI: 2.58 to 4.92; p < 0.00001), proteinuria (RR = 1.89; 95 % CI: 1.26 to 2.84; p = 0.002), gastrointestinal perforation (RR = 3.63; 95 % CI: 1.31 to 10.09; p = 0.01), any thromboembolic events (RR = 1.44; 95 % CI: 1.20 to 1.73; p = 0.0001), and bleeding (RR = 1.81; 95 % CI: 1.22 to 2.67; p = 0.003). The combination of chemotherapy with bevacizumab increased the response rate, progression-free survival and overall survival of patients with mCRC without prior chemotherapy. The results of progression-free survival (PFS) and overall survival (OS) were comparatively higher

Human survivability of extreme impacts in free-fall.

Science.gov (United States)

1963-08-01

Human deceleration tolerances beyond the limits imposed by voluntary experimental methods were studied by means of intensive case histories of 137 individuals who have survived extremely abrupt impacts in accidental, suicidal, and homicidal free-fall...

Should high risk patients with Hodgkin's disease be singled out for heavier therapeutic regimens while low risk patients are spared such therapies?

Science.gov (United States)

Reece, D

1995-01-01

In order to optimize the use of intensive therapy and autologous transplantation in patients with progressive Hodgkin's disease, we have examined the outcome of our initial 100 patients entered into autograft studies between 1985 and 1992. At a median follow-up of 3.6 (range 1.6-8.2) years, the actuarial progression free survival (PFS) was 46% (95% confidence intervals 33%-57%). The most significant determinant of PFS was the disease status at the time of protocol entry. Patients entered into transplant studies at the time of first untested relapse had a PFS of 61% compared with 38% in those who had failed induction chemotherapy, 25% in patients treated in > or = second untested relapse and 0% in those in a chemoresistant relapse. The reasons for failure differed, however, in that a high non-relapse mortality was seen in the > or = second untested relapse and resistant relapse groups while a high probability of relapse was observed in the induction failures and resistant relapse group. The most obvious group to target with more intensive therapeutic regimens consists of patients who have failed induction chemotherapy.

Long-Term Efficacy of Maintenance Therapy for Multiple Myeloma: A Quantitative Synthesis of 22 Randomized Controlled Trials

Directory of Open Access Journals (Sweden)

Jie-Li Li

2018-04-01

Full Text Available We aimed to quantitatively synthesize data from randomized controlled trials (RCTs concerning maintenance for multiple myeloma (MM. We searched electronic literature databases and conference proceedings to identify relevant RCTs. We selected eligible RCTs using predefined selection criteria. We conducted meta-analysis comparing maintenance containing new agents and conventional maintenance, and subgroup analysis by transplantation status and mainstay agent as well. We performed trial sequential analysis (TSA to determine adequacy of sample size for overall and subgroup meta-analyses. We performed network meta-analysis (NMA to compare and rank included regimens. A total of 22 RCTs involving 9,968 MM patients and 15 regimens were included, the overall quality of which was adequate. Significant heterogeneity was detected for progression-free survival (PFS but not overall survival (OS. Meta-analyses showed that maintenance containing new agents significantly improved PFS but not OS [PFS: Hazard Ratio (HR = 0.59, 95% Confidence Interval (CI = 0.54 to 0.64; OS: HR = 0.93, 95% CI = 0.87 to 1.00], compared with controls. Subgroup analyses revealed lenalidomide (Len-based therapies better than thalidomide-based ones (HR = 0.50 and 0.66, respectively; P = 0.001. NMA revealed that most of the maintenance regimens containing new agents were significantly better than simple observation in terms of PFS but not OS. Len single agent was the most effective, considering PFS and OS both. We concluded that conventional maintenance has very limited effect. Maintenance containing new agents is highly effective in improving PFS, but has very limited effect on OS. Maintenance with Len may have the largest survival benefits. Emerging strategies may further change the landscape of maintenance of MM.

The prognostic value of derived neutrophil to lymphocyte ratio in oesophageal cancer treated with definitive chemoradiotherapy.

Science.gov (United States)

Cox, Samantha; Hurt, Christopher; Grenader, Tal; Mukherjee, Somnath; Bridgewater, John; Crosby, Thomas

2017-10-01

The derived neutrophil-lymphocyte ratio (dNLR) is a validated prognostic biomarker for cancer survival but has not been extensively studied in locally-advanced oesophageal cancer treated with definitive chemoradiotherapy (dCRT). We aimed to identify the prognostic value of dNLR in patients recruited to the SCOPE1 trial. 258 patients were randomised to receive dCRT±cetuximab. Kaplan-Meier's curves and both univariable and multivariable Cox regression models were calculated for overall survival (OS), progression free survival (PFS), local PFS inside the radiation volume (LPFSi), local PFS outside the radiation volume (LPFSo), and distant PFS (DPFS). An elevated pre-treatment dNLR≥2 was significantly associated with decreased OS in univariable (HR 1.74 [95% CI 1.29-2.35], p<0.001) and multivariable analyses (HR 1.64 [1.17-2.29], p=0.004). Median OS was 36months (95% CI 27.8-42.4) if dNLR<2 and 18.4months (95% CI 14.1-24.9) if dNLR≥2. All measures of PFS were also significantly reduced with an elevated dNLR. dNLR was prognostic for OS in cases of squamous cell carcinoma with a non-significant trend for adenocarcinoma/undifferentiated tumours. An elevated pre-treatment dNLR may be an independent prognostic biomarker for OS and PFS in oesophageal cancer patients treated with definitive CRT. dNLR is a simple, inexpensive and readily available tool for risk-stratification and should be considered for use in future oesophageal cancer clinical trials. The SCOPE1 trial was an International Standard Randomised Controlled Trial [number 47718479]. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Prognostic factors, patterns of recurrence and toxicity for patients with esophageal cancer undergoing definitive radiotherapy or chemo-radiotherapy

International Nuclear Information System (INIS)

Haefner, Matthias F.; Lang, Kristin; Krug, David; Koerber, Stefan A.; Debus, Juergen; Sterzing, Florian; Uhlmann, Lorenz; Kieser, Meinhard

2015-01-01

The aim of this study was to evaluate the effectiveness and tolerability of definitive chemo-radiation or radiotherapy alone in patients with esophageal cancer. We retrospectively analyzed the medical records of n = 238 patients with squamous cell carcinoma or adenocarcinoma of the esophagus treated with definitive radiotherapy with or without concomitant chemotherapy at our institution between 2000 and 2012. Patients of all stages were included to represent actual clinical routine. We performed univariate and multivariate analysis to identify prognostic factors for overall survival (OS) and progression-free survival (PFS). Moreover, treatment-related toxicity and patterns of recurrence were assessed. Patients received either chemo-radiation (64%), radiotherapy plus cetuximab (10%) or radiotherapy alone (26%). In 69%, a boost was applied, resulting in a median cumulative dose of 55.8 Gy; the remaining 31% received a median total dose of 50 Gy. For the entire cohort, the median OS and PFS were 15.0 and 11.0 months, respectively. In multivariate analysis, important prognostic factors for OS and PFS were T stage (OS: P = 0.005; PFS: P = 0.006), M stage (OS: P = 0.015; PFS: P = 0.003), concomitant chemotherapy (P < 0.001) and radiation doses of >55 Gy (OS: P = 0.019; PFS: P = 0.022). Recurrences occurred predominantly as local in-field relapse or distant metastases. Toxicity was dominated by nutritional impairment (12.6% with G3/4 dysphagia) and chemo-associated side effects. Definitive chemo-radiation in patients with esophageal cancer results in survival rates comparable with surgical treatment approaches. However, local and distant recurrence considerably restrict prognosis. Further advances in radio-oncological treatment strategies are necessary for improving outcome. (author)

Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer: Extended Analysis of the Phase 3 PREVAIL Study.

Science.gov (United States)

Beer, Tomasz M; Armstrong, Andrew J; Rathkopf, Dana; Loriot, Yohann; Sternberg, Cora N; Higano, Celestia S; Iversen, Peter; Evans, Christopher P; Kim, Choung-Soo; Kimura, Go; Miller, Kurt; Saad, Fred; Bjartell, Anders S; Borre, Michael; Mulders, Peter; Tammela, Teuvo L; Parli, Teresa; Sari, Suha; van Os, Steve; Theeuwes, Ad; Tombal, Bertrand

2017-02-01

Enzalutamide significantly improved radiographic progression-free survival (rPFS) and overall survival (OS) among men with chemotherapy-naïve metastatic castration-resistant prostate cancer at the prespecified interim analysis of PREVAIL, a phase 3, double-blind, randomized study. We evaluated the longer-term efficacy and safety of enzalutamide up to the prespecified number of deaths in the final analysis, which included an additional 20 mo of follow-up for investigator-assessed rPFS, 9 mo of follow-up for OS, and 4 mo of follow-up for safety. Enzalutamide reduced the risk of radiographic progression or death by 68% (hazard ratio [HR] 0.32, 95% confidence interval [CI] 0.28-0.37; pPREVAIL provides more complete assessment of the clinical benefit of enzalutamide. PREVAIL is registered on ClinicalTrials.gov as NCT01212991. According to data from longer follow-up, enzalutamide continued to provide benefit over placebo in patients with metastatic castration-resistant prostate cancer. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Statin use is not associated with improved progression free survival in cetuximab treated KRAS mutant metastatic colorectal cancer patients: results from the CAIRO2 study.

Directory of Open Access Journals (Sweden)

Lisanne L Krens

Full Text Available Statins may inhibit the expression of the mutant KRAS phenotype by preventing the prenylation and thus the activation of the KRAS protein. This study was aimed at retrospectively evaluating the effect of statin use on outcome in KRAS mutant metastatic colorectal cancer patients (mCRC treated with cetuximab. Treatment data were obtained from patients who were treated with capecitabine, oxaliplatin bevacizumab ± cetuximab in the phase III CAIRO2 study. A total of 529 patients were included in this study, of whom 78 patients were on statin therapy. In patients with a KRAS wild type tumor (n = 321 the median PFS was 10.3 vs. 11.4 months for non-users compared to statin users and in patients with a KRAS mutant tumor (n = 208 this was 7.6 vs. 6.2 months, respectively. The hazard ratio (HR for PFS for statin users was 1.12 (95% confidence interval 0.78-1.61 and was not influenced by treatment arm, KRAS mutation status or the KRAS*statin interaction. Statin use adjusted for covariates was not associated with increased PFS (HR = 1.01, 95% confidence interval 0.71-1.54. In patients with a KRAS wild type tumor the median OS for non-users compared to statin users was 22.4 vs. 19.8 months and in the KRAS mutant tumor group the OS was 18.1 vs. 14.5 months. OS was significantly shorter in statin users versus non-users (HR = 1.54; 95% confidence interval 1.06-2.22. However, statin use, adjusted for covariates was not associated with increased OS (HR = 1.41, 95% confidence interval 0.95-2.10. In conclusion, the use of statins at time of diagnosis was not associated with an improved PFS in KRAS mutant mCRC patients treated with chemotherapy and bevacizumab plus cetuximab.

Rationale and design of decision: a double-blind, randomized, placebo-controlled phase III trial evaluating the efficacy and safety of sorafenib in patients with locally advanced or metastatic radioactive iodine (RAI)-refractory, differentiated thyroid cancer

International Nuclear Information System (INIS)

Brose, Marcia S; Schlumberger, Martin; Nutting, Christopher M; Sherman, Steven I; Shong, Young Kee; Smit, Johannes WA; Reike, Gerhard; Chung, John; Kalmus, Joachim; Kappeler, Christian

2011-01-01

The incidence of thyroid cancer and the number of patients who die from this disease are increasing globally. Differentiated thyroid cancer (DTC) is the histologic subtype present in most patients and is primarily responsible for the increased overall incidence of thyroid cancer. Sorafenib is a multikinase inhibitor that targets several molecular signals believed to be involved in the pathogenesis of thyroid cancer, including those implicated in DTC. In phase II studies of patients with DTC, sorafenib treatment has yielded a median progression-free survival (PFS) of 58 to 84 weeks and disease control rates of 59% to 100%. The DECISION trial was designed to assess the ability of sorafenib to improve PFS in patients with locally advanced or metastatic, radioactive iodine (RAI)-refractory DTC. DECISION is a multicenter, double-blind, randomized, placebo-controlled phase III study in patients with locally advanced/metastatic RAI-refractory DTC. Study treatment will continue until radiographically documented disease progression, unacceptable toxicity, noncompliance, or withdrawal of consent. Efficacy will be evaluated every 56 days (2 cycles), whereas safety will be evaluated every 28 days (1 cycle) for the first 8 months and every 56 days thereafter. Following disease progression, patients may continue or start sorafenib, depending on whether they were randomized to receive sorafenib or placebo, at investigator discretion. Patients originally randomized to receive sorafenib will be followed up every 3 months for overall survival (OS); patients originally randomized to receive placebo will be followed up every month for 8 months after cross-over to sorafenib. The duration of the trial is expected to be 30 months from the time the first patient is randomized until the planned number of PFS events is attained. The primary endpoint is PFS; secondary endpoints include OS, time to disease progression, disease control rate, response rate, duration of response, safety, and

Long-term outcomes for adult craniopharyngioma following radiation therapy

Energy Technology Data Exchange (ETDEWEB)

Masson-Cote, Laurence; Masucci, Giuseppina Laura; Millar, Barbara-Ann; Laperriere, Normand J. [Dept. of Radiation Oncology, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada); Atenafu, Eshetu G. [Dept. of Biostatistics, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada); Cusimano, Michael [Dept. of Surgery, Div. of Neurosurgery, St. Michaels Hospital, Toronto (Canada); Croul, Sidney [Dept. of Pathology, Univ. of Toronto, Toronto (Canada); Mason, Warren [Dept. of Medicine, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada); Sahgal, Arjun [Dept. of Radiation Oncology, Princess Margaret Hospital, Univ. of Toronto, Toronto (Canada), E-mail: Arjun.sahgal@rmp.uhn.on.ca; Dept. of Radiation Oncology, Sunnybrook Health Sciences Center, Univ. of Toronto, Toronto (Canada)

2013-01-15

Background. We report long-term outcomes in adult patients with craniopharyngioma following surgery and radiation therapy (RT). Material and methods. Fifty-three patients treated with RT (median, 50 Gy in 25 fractions) between 1980 and 2009 with pathologically confirmed craniopharyngioma were reviewed (53% solid and 47% cystic/solid). The median age was 53 years (range, 22-76), 53% were female, 83% were sub-totally resected, 6% were gross totally resected and 11% had a biopsy and/or cyst aspiration alone. RT was delivered adjuvantly in 53% of patients as opposed to salvage intent upon progression. Results. Median follow-up was seven years (86 months, range, 8-259). The 5- and 10-year progression-free survival (PFS) rates were 85% and 69%, overall survival (OS) rates were 76% and 70%, and cause-specific survival (CSS) rates were both 88%, respectively. Both univariable and multivariable analysis identified age (<53 or {>=}53) as a prognostic factor for OS (p =0.0003) and CSS (p =0.05). PFS was observed to be worse in patients with >2 surgeries prior to RT (p =0.01). Neither the intent of radiation or tumor type (cystic vs. solid/cystic) were prognostic or predictive. New endocrinopathies and visual dysfunction were observed in 53% and 17% of patients post-surgery, and in 11% and 6% post-RT, respectively. Conclusion. We report long-term favorable PFS, CSS and OS for craniopharyngioma post-RT. We observe age as a significant prognostic factor, however, timing of radiation was not.

Adoptive cell transfer after chemotherapy enhances survival in patients with resectable HNSCC.

Science.gov (United States)

Jiang, Pan; Zhang, Yan; J Archibald, Steve; Wang, Hua

2015-09-01

The aims of this study were to evaluate the therapeutic efficacy and to determine the immune factors for treatment success in patients with head and neck squamous cell carcinoma (HNSCC) treated with chemotherapy followed by adoptive cell transfer (ACT). A total of 43 HNSCC patients who received radical resection and chemotherapy were analysed in this study. Twenty-one of the patients were repeatedly treated with ACT after chemotherapy (ACT group), and the other twenty-two patients without ACT treatment were included as part of the control group. To investigate the immunological differences underlying these observations, we expanded and profiled improving cytokine-induced killer cells (iCIK) from peripheral blood mononuclear cells (PBMCs) with the timed addition of RetroNectin, OKT3 mAb, IFN γ and IL-2. The median of progression-free survival (PFS) and overall survival (OS) in the ACT group were significantly higher as compared to the control group (56 vs. 40; 58 vs. 45 months). In iCIK culture, there was a significant reduction in CD3+CD4+ T-cell proliferation and cytokines (IL-2, TNF) production from patients who received chemotherapy compared to patients without chemotherapy. Intra-arterial infusion of iCIK, in coordination with chemotherapy, considerably rescued iCIK culture from the suppression of systemic immunity induced by chemotherapy and induced tumour regression. Altogether, these findings suggest that ACT is an effective neo-adjuvant therapy for rescuing systemic immune suppression and improving survival time in patients with HNSCC. Copyright © 2015 Elsevier B.V. All rights reserved.

Clinical Experience With Radiation Therapy in the Management of Neurofibromatosis-Associated Central Nervous System Tumors

International Nuclear Information System (INIS)

Wentworth, Stacy; Pinn, Melva; Bourland, J. Daniel; Guzman, Allan F. de; Ekstrand, Kenneth; Ellis, Thomas L.; Glazier, Steven S.; McMullen, Kevin P.; Munley, Michael; Stieber, Volker W.; Tatter, Stephen B.; Shaw, Edward G.

2009-01-01

Purpose: Patients with neurofibromatosis (NF) develop tumors of the central nervous system (CNS). Radiation therapy (RT) is used to treat these lesions. To better define the efficacy of RT in these patients, we reviewed our 20-year experience. Methods and Materials: Eighteen patients with NF with CNS tumors were treated from 1986 to 2007. Median follow-up was 48 months. Progression was defined as growth or recurrence of an irradiated tumor on serial imaging. Progression-free survival (PFS) was measured from the date of RT completion to the date of last follow-up imaging study. Actuarial rates of overall survival (OS) and PFS were calculated according to the Kaplan-Meier method. Results: Eighty-two tumors in 18 patients were irradiated, with an average of five tumors/patient. Median age at treatment was 25 years (range, 4.3-64 years). Tumor types included acoustic neuroma (16%), ependymoma (6%), low-grade glioma (11%), meningioma (60%), and schwanomma/neurofibroma (7%). The most common indication for treatment was growth on serial imaging. Most patients (67%) received stereotactic radiosurgery (median dose, 1,200 cGy; range, 1,000-2,400 cGy). The OS rate at 5 years was 94%. Five-year PFS rates were 75% (acoustic neuroma), 100% (ependymoma), 75% (low-grade glioma), 86% (meningioma), and 100% (schwanomma/neurofibroma). Thirteen acoustic neuromas had a local control rate of 94% with a 50% hearing preservation rate. Conclusions: RT provided local control, OS, and PFS rates similar to or better than published data for tumors in non-NF patients. Radiation therapy should be considered in NF patients with imaging progression of CNS tumors

A phase II evaluation of ixabepilone in the treatment of recurrent/persistent carcinosarcoma of the uterus, an NRG Oncology/Gynecologic Oncology Group study.

Science.gov (United States)

McCourt, Carolyn K; Deng, Wei; Dizon, Don S; Lankes, Heather A; Birrer, Michael J; Lomme, Michele M; Powell, Matthew A; Kendrick, James E; Saltzman, Joel N; Warshal, David; Tenney, Meaghan E; Kushner, David M; Aghajanian, Carol

2017-01-01

The primary objectives were to determine the objective response rate (ORR) and safety profile of ixabepilone in women with recurrent or persistent uterine carcinosarcoma (UCS). Secondary objectives included progression-free survival (PFS) and overall survival (OS). Exploratory translational objectives included characterization of class III beta tubulin expression and its association with response, PFS, and OS. Patients had measurable disease; up to two prior chemotherapeutic regimens were allowed, but must have included a taxane. Women received ixabepilone 40mg/m 2 as a 3hour IV infusion on day 1 of a 21daycycle. Treatment was continued until disease progression or unacceptable toxicity occurred. Forty-two women were enrolled, with 34 eligible and evaluable. Median age was 68years. ECOG performance status was 0 in 56% of women, 38% had received radiation, and 15% had received 2 lines of chemotherapy. Overall ORR was 11.8% (4/34, 90% CI 4.2-25.1%); all were partial responses. Stable disease for at least 8weeks was achieved in 8 patients (23.5%). Median PFS and OS were 1.7mo and 7.7mo, respectively, with a median follow-up of 37mo. Six month PFS was 20.6%. Major grade≥3 toxicities were neutropenia (47%), fatigue (15%), dehydration (15%), hypertension (15%), and hyponatremia (15%); grade 2 peripheral neuropathy was reported in 18%. In this small sample size, class III beta tubulin expression in the primary tumor was not associated with the response to ixabepilone, PFS, or OS. In this cohort of women, single agent ixabepilone showed modest but insufficient clinical activity. Copyright © 2016. Published by Elsevier Inc.

Afatinib versus gefitinib in patients with EGFR mutation-positive advanced non-small-cell lung cancer: overall survival data from the phase IIb LUX-Lung 7 trial.

Science.gov (United States)

Paz-Ares, L; Tan, E-H; O'Byrne, K; Zhang, L; Hirsh, V; Boyer, M; Yang, J C-H; Mok, T; Lee, K H; Lu, S; Shi, Y; Lee, D H; Laskin, J; Kim, D-W; Laurie, S A; Kölbeck, K; Fan, J; Dodd, N; Märten, A; Park, K

2017-02-01

In LUX-Lung 7, the irreversible ErbB family blocker, afatinib, significantly improved progression-free survival (PFS), time-to-treatment failure (TTF) and objective response rate (ORR) versus gefitinib in patients with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). Here, we present primary analysis of mature overall survival (OS) data. LUX-Lung 7 assessed afatinib 40 mg/day versus gefitinib 250 mg/day in treatment-naïve patients with stage IIIb/IV NSCLC and a common EGFR mutation (exon 19 deletion/L858R). Primary OS analysis was planned after ∼213 OS events and ≥32-month follow-up. OS was analysed by a Cox proportional hazards model, stratified by EGFR mutation type and baseline brain metastases. Two-hundred and twenty-six OS events had occurred at the data cut-off (8 April 2016). After a median follow-up of 42.6 months, median OS (afatinib versus gefitinib) was 27.9 versus 24.5 months [hazard ratio (HR) = 0.86, 95% confidence interval (CI) 0.66‒1.12, P = 0.2580]. Prespecified subgroup analyses showed similar OS trends (afatinib versus gefitinib) in patients with exon 19 deletion (30.7 versus 26.4 months; HR, 0.83, 95% CI 0.58‒1.17, P = 0.2841) and L858R (25.0 versus 21.2 months; HR 0.91, 95% CI 0.62‒1.36, P = 0.6585) mutations. Most patients (afatinib, 72.6%; gefitinib, 76.8%) had at least one subsequent systemic anti-cancer treatment following discontinuation of afatinib/gefitinib; 20 (13.7%) and 23 (15.2%) patients received a third-generation EGFR tyrosine kinase inhibitor. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib. In LUX-Lung 7, there was no significant difference in OS with afatinib versus gefitinib. Updated PFS (independent review), TTF and ORR data were significantly improved with afatinib. NCT01466660. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology.

Outcome of Patients With Pilocytic Astrocytoma and Leptomeningeal Dissemination

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Mazloom, Ali; Hodges, Joseph C.; Teh, Bin S. [Department of Radiation Oncology, Methodist Hospital, Houston, TX (United States); Chintagumpala, Murali [Department of Pediatrics, Baylor College of Medicine, Houston, TX (United States); Paulino, Arnold C., E-mail: apaulino@tmhs.org [Department of Radiation Oncology, Methodist Hospital, Houston, TX (United States); Department of Pediatrics, Baylor College of Medicine, Houston, TX (United States)

2012-10-01

Purpose: To determine the patient, tumor, and treatment characteristics of patients with pilocytic astrocytoma (PA) and leptomeningeal dissemination (LMD). Methods and Materials: A PubMed search of English-language studies pertaining to PA with LMD was performed using a combination of keywords that included juvenile pilocytic astrocytoma, low-grade astrocytoma, low-grade glioma, leptomeningeal dissemination, neuraxis spread, and radiotherapy. We found 26 studies with 58 patients between 1976 and 2005 that met these criteria. Results: The median survival for PA patients with LMD was 65 months. The 1-, 2-, and 5-year overall survival (OS) rate after the diagnosis of LMD was 81.1%, 75.7%, and 55.5%. The 1-, 2-, and 5-year progression-free survival (PFS) rate after the diagnosis of LMD was 69.3%, 66.5%, and 34.6%, respectively. Age, gender, primary site location, timing of LMD presentation (synchronous vs. metachronous), and LMD location did not significantly influence OS or PFS. No statistically significant difference was found in OS or PFS between the chemotherapy and radiotherapy groups. Likewise, no difference was found in OS or PFS according to the use of craniospinal irradiation vs. less extensive RT fields. Conclusions: Approximately one-half of PA patients were alive 5 years after the diagnosis of LMD. Both chemotherapy and radiotherapy have efficacy against LMD. Although the use of craniospinal irradiation did not have an effect on PFS, the patient numbers were small and a larger number treated with craniospinal irradiation is needed to determine its efficacy.

Analysis of treatment outcomes for primary tonsillar lymphoma

Energy Technology Data Exchange (ETDEWEB)

Lee, Yun Hee [Dept. of Radiation Oncology, Gyeongsang National University Hospital, Gyeongsang National University School of Medicine, Jinju (Korea, Republic of); Cho, Seok Goo; Jung, Seung Eun; Kim, Sung Hoon; O, Joo Hyun; Park, Gyeong Sin; Yang, Suk Woo; Lee, In Seok; Rhee, Chin; Kook; Choi, Byung Ock [Catholic University Lymphoma Group (CULG), Seoul St. Mary' s Hospital, College of Medicine, The Catholic University of Korea, Seoul (Korea, Republic of)

2016-12-15

Although each Waldeyer’s ring sub-site is considered an independent prognostic factor, few studies have assessed the prognosis and treatment of tonsillar lymphoma. Treatment outcomes were analyzed in patients with primary tonsillar lymphoma who were treated with chemotherapy and radiotherapy (RT). Nineteen patients with diffuse large B-cell lymphoma were evaluated, with a median follow-up of 53 months. Age, sex, and histology, amongst other factors, were reviewed. Progression-free survival (PFS) and overall survival (OS) rates were analyzed. Most patients had Ann Arbor stage I-II (94.7%), IPI score of 0 (89.5%), and complete remission after chemotherapy (89.5%). The 5-year PFS and OS rates were 74.6% and 80%, respectively. In univariate analysis, the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) regimen resulted in a better PFS than the cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) regimen (88.9% vs. 50.0%; p = 0.053). RT dose was related to the survival outcome (p = 0.010 for PFS, p = 0.044 for OS). Patients were classified into the CHOP + RT (>40 Gy) group and R-CHOP + RT (≤40 Gy) group. The 5-year PFS rates were 50% in the CHOP + RT group, and 100 % in the R-CHOP + RT group (p = 0.018). The 5-year OS rates were 66.7% and 100%, respectively (p = 0.087). Primary tonsillar lymphoma patients typically have favorable outcomes. Chemotherapy (R-CHOP) combined with relatively lower dose consolidative RT may be safe and effective for primary tonsillar lymphoma.

Prognostic value of HER-2/neu expression in epithelial ovarian cancer: a systematic review and meta-analysis.

Science.gov (United States)

Wang, Kai; Guan, Chenan; Yu, Junhui; Jin, Xiaoxiao; Sun, Ling; Zheng, Lingzhi; Xia, Liang; Zhang, Yuquan

2017-09-26

This study aimed to conduct a meta-analysis to investigate the association between human epidermal growth factor receptor 2 (HER-2/neu) expression and survival in patients with epithelial ovarian cancer (EOC). HER-2/neu is one of the most frequently studied molecular biological parameters in EOC, but its prognostic impact has not been fully assessed. PubMed and Embase were searched for studies that reported HER-2/neu expression and survival in patients with EOC. The primary outcome was overall survival (OS), and the secondary outcome was progression-free survival (PFS). Hazard ratios (HRs) with 95% confidence interval (CI) were determined using Mantel-Haenszel random-effects model. Publication bias was investigated using funnel plots and Egger's test. A total of 56 studies (N=7212) were included in the analysis. The results showed that patients possessing HER-2/neu expression had significant disadvantages in OS (HR = 1.41; 95%CI, 1.31 to 1.51; P present study findings provided further indication that HER-2/neu expression in patients with EOC has an adverse impact on OS and PFS.

Prognostic Value of FDG-PET, Based on the Revised Response Criteria, in Patients with Malignant Lymphoma: A Comparison with CT/MRI Evaluations, Based on the International Working Group/ Cotswolds Meeting Criteria

Directory of Open Access Journals (Sweden)

Kayako Isohashi

2015-07-01

Full Text Available Objective(s: Post-treatment evaluations by CT/MRI (based on the International Working Group/ Cotswolds meeting guidelines and PET (based on Revised Response Criteria, were examined in terms of progression-free survival (PFS in patients with malignant lymphoma (ML. Methods: 79 patients, undergoing CT/MRI for the examination of suspected lesions and whole-body PET/CT before and after therapy, were included in the study during April 2007-January 2013. The relationship between post-treatment evaluations (CT/MRI and PET and PFS during the follow-up period was examined, using Kaplan-Meier survival analysis. The patients were grouped according to the histological type into Hodgkin’s lymphoma (HL, diffuse large B-cell lymphoma (DLBCL, and other histological types. The association between post-treatment evaluations (PET or PET combined with CT/ MRI and PFS was examined separately. Moreover, the relationship between disease recurrence and serum soluble interleukin-2 receptor, lactic dehydrogenase, and C-reactive protein levels was evaluated before and after the treatment. Results: Patients with incomplete remission on both CT/MRI and PET had a significantly shorter PFS, compared to patients with complete remission on both CT/MRI and PET and those exhibiting incomplete remission on CT/MRI and complete remission on PET (P

Prognostic significance of focal lesions and diffuse infiltration on MRI for multiple myeloma: a meta-analysis

Energy Technology Data Exchange (ETDEWEB)

Lee, So-Yeon; Park, Hee-Jin [Sungkyunkwan University School of Medicine, Department of Radiology, Kangbuk Samsung Hospital, Seoul (Korea, Republic of); Kim, Hyun-Jung [Korea University College of Medicine, Department of Preventive Medicine, Seoul (Korea, Republic of); Shin, Yu Ri [The Catholic University of Korea, Department of Radiology, Incheon St. Mary' s Hospital, College of Medicine, Seoul (Korea, Republic of); Lee, Yun-Gyoo; Oh, Suk Joong [Sungkyunkwan University School of Medicine, Division of Hematology and Oncology, Department of Internal Medicine, Kangbuk Samsung Hospital, Seoul (Korea, Republic of)

2017-06-15

MRI of bone marrow of the axial skeleton is recommended for evaluation of multiple myeloma. The impact of bone marrow involvement pattern on MRI for determining progression-free survival (PFS) and overall survival (OS) is not yet clear. We performed a meta-analysis of research on the prognostic significance of MRI patterns for OS and PFS using a random effects model. Databases searched without language restriction were MEDLINE, EMBASE, and the Cochrane Library (January 1976 to April 2014). Manual searches were also conducted. Of 10,953 citations identified in the original search, 10 cohort studies for a total of 2015 patients met the inclusion criteria. Nine of the 10 included studies are from three research groups. Pooled hazard ratios were 1.80 (95 % confidence interval [CI] 1.32-2.46; P < 0.001) for OS and 2.30 (95 % CI 1.65-3.20; P < 0.001) for PFS for focal lesions on MRI; and 1.70 (95 % CI 1.30-2.21; P < 0.001) for OS and 1.74 (95 % CI 1.07-2.85; P = 0.03) for PFS for diffuse infiltration on MRI. No significant heterogeneity was observed among studies. This meta-analysis demonstrated an association between focal lesions and diffuse infiltration and poor prognosis in this population. (orig.)

Safety and efficacy of high-dose tamoxifen and sulindac for desmoid tumor in children: results of a Children's Oncology Group (COG) phase II study.

Science.gov (United States)

Skapek, Stephen X; Anderson, James R; Hill, D Ashley; Henry, David; Spunt, Sheri L; Meyer, William; Kao, Simon; Hoffer, Fredric A; Grier, Holcombe E; Hawkins, Douglas S; Raney, R Beverly

2013-07-01

Desmoid fibromatosis (desmoid tumor, DT) is a soft tissue neoplasm prone to recurrence despite complete surgical resection. Numerous small retrospective reports suggest that non-cytotoxic chemotherapy using tamoxifen and sulindac may be effective for DT. We evaluated the safety and efficacy of tamoxifen and sulindac in a prospective phase II study within the Children's Oncology Group. Eligible patients were <19 years of age who had measurable DT that was recurrent or not amenable to surgery or radiation. The primary objective was to estimate progression-free survival (PFS). Patients received tamoxifen and sulindac daily for 12 months or until disease progression or intolerable toxicity occurred. Response was assessed by magnetic resonance imaging. Fifty-nine eligible patients were enrolled from 2004 to 2009; 78% were 10-18 years old. Twenty-two (38%) were previously untreated; 15 (41%) of the remaining 37 enrolling with recurrent DT had prior systemic chemotherapy and six (16%) had prior radiation. No life-threatening toxicity was reported. Twelve (40%) of 30 females developed ovarian cysts, which were asymptomatic in 11 cases. Ten patients completed therapy without disease progression or discontinuing treatment. Responses included four partial and one complete (5/59, 8%). The estimated 2-year PFS and survival rates were 36% (95% confidence interval: 0.23-0.48) and 96%, respectively. All three deaths were due to progressive DT. Tamoxifen and sulindac caused few serious side effects in children with DT, although ovarian cysts were common. However, the combination showed relatively little activity as measured by response and PFS rates. Copyright © 2012 Wiley Periodicals, Inc.

Safety and Efficacy of High-Dose Tamoxifen and Sulindac for Desmoid Tumor in Children: Results of a Children’s Oncology Group (COG) Phase II Study

Science.gov (United States)

Skapek, Stephen X.; Anderson, James R.; Hill, D. Ashley; Henry, David; Spunt, Sheri L.; Meyer, William; Kao, Simon; Hoffer, Fredric A.; Grier, Holcombe E.; Hawkins, Douglas S.; Raney, R. Beverly

2015-01-01

Background Desmoid fibromatosis (desmoid tumor, DT) is a soft tissue neoplasm prone to recurrence despite complete surgical resection. Numerous small retrospective reports suggest that non-cytotoxic chemotherapy using tamoxifen and sulindac may be effective for DT. We evaluated the safety and efficacy of tamoxifen and sulindac in a prospective phase II study within the Children’s Oncology Group. Procedures Eligible patients were <19 years of age who had measurable DT that was recurrent or not amenable to surgery or radiation. The primary objective was to estimate progression-free survival (PFS). Patients received tamoxifen and sulindac daily for 12 months or until disease progression or intolerable toxicity occurred. Response was assessed by magnetic resonance imaging. Results Fifty-nine eligible patients were enrolled from 2004 to 2009; 78% were 10–18 years old. Twenty-two (38%) were previously untreated; 15 (41%) of the remaining 37 enrolling with recurrent DT had prior systemic chemotherapy and six (16%) had prior radiation. No life-threatening toxicity was reported. Twelve (40%) of 30 females developed ovarian cysts, which were asymptomatic in 11 cases. Ten patients completed therapy without disease progression or discontinuing treatment. Responses included four partial and one complete (5/59, 8%). The estimated 2-year PFS and survival rates were 36% (95% confidence interval: 0.23–0.48) and 96%, respectively. All three deaths were due to progressive DT. Conclusions Tamoxifen and sulindac caused few serious side effects in children with DT, although ovarian cysts were common. However, the combination showed relatively little activity as measured by response and PFS rates. PMID:23281268

Association of TERT Polymorphisms with Clinical Outcome of Non-Small Cell Lung Cancer Patients.

Directory of Open Access Journals (Sweden)

Xueying Zhao

Full Text Available TERT is of great importance in cancer initiation and progression. Many studies have demonstrated the TERT polymorphisms as risk factors for many cancer types, including lung cancer. However, the impacts of TERT variants on cancer progression and treatment efficacy have remained controversial. This study aimed to investigate the association of TERT polymorphisms with clinical outcome of advanced non-small cell lung cancer (NSCLC patients receiving first-line platinum-based chemotherapy, including response rate, clinical benefit, progression-free survival (PFS, overall survival (OS, and grade 3 or 4 toxicity. Seven polymorphisms of TERT were assessed, and a total of 1004 inoperable advanced NSCLC patients treated with platinum-based chemotherapy were enrolled. It is exhibited that the variant heterozygote of rs4975605 showed significant association with a low rate of clinical benefit, and displayed a much stronger effect in never-smoking female subset, leading to the clinical benefit rate decreased from 82.9% (C/C genotype to 56.4% (C/A genotype; adjusted OR, 3.58; P=1.40×10(-4. It is also observed that the polymorphism rs2736109 showed significant correlation with PFS (log-rank P=0.023. In age > 58 subgroup, patients carrying the heterozygous genotype had a longer median PFS than those carrying the wild-type genotypes (P=0.002. The results from the current study, for the first time to our knowledge, provide suggestive evidence of an effect of TERT polymorphisms on disease progression variability among Chinese patients with platinum-treated advanced NSCLC.

A case report of long term bevacizumab treatment in multiresistant ovarian cancer

DEFF Research Database (Denmark)

Kargo, Anette Stolberg; Adimi, Parvin; Dahl-Steffensen, Karina

2016-01-01

Treatment of multiresistant ovarian cancer is palliative and patients have needs for less toxic treatment. Anti-angiogenic treatments have a less toxic profile, and bevacizumab has shown improvement of progression free survival (PFS) in front-line trials. Bevacizumab is generally introduced in co...... in combination with chemotherapy; however this case report will describe the use of single-agent bevacizumab for more than five years (102 cycles) in a patient with relapse of advanced ovarian cancer...

Randomized Phase II Trial of Adjuvant WT-1 Analog Peptide Vaccine in Patients with Malignant Pleural Mesothelioma after Completion of Multimodality Therapy

Science.gov (United States)

2017-11-01

cellular proliferation, differentiation, apoptosis, organ development, and sex determination , the protein is processed by the proteasome and the derived...peptide). Vaccine:  2/3 CD8+  4/8 CD4+ Control:  0/4 CD8+  1/8 CD4+ Injection site reactions were common, mild, and self -limited...the ASCO Annual Meeting 2016. 3 Abstract Purpose: Determine the 1-year progression-free survival (PFS) among patients with malignant pleural

Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

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Tao, Randa; Allen, Pamela K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Rodriguez, Alma [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Shihadeh, Ferial; Pinnix, Chelsea C.; Arzu, Isadora; Reed, Valerie K. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Oki, Yasuhiro; Westin, Jason R.; Fayad, Luis E.; Medeiros, L. Jeffrey [Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Dabaja, Bouthaina, E-mail: bdabaja@mdanderson.org [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2015-05-01

Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS.

Benefit of Consolidative Radiation Therapy for Primary Bone Diffuse Large B-Cell Lymphoma

International Nuclear Information System (INIS)

Tao, Randa; Allen, Pamela K.; Rodriguez, Alma; Shihadeh, Ferial; Pinnix, Chelsea C.; Arzu, Isadora; Reed, Valerie K.; Oki, Yasuhiro; Westin, Jason R.; Fayad, Luis E.; Medeiros, L. Jeffrey; Dabaja, Bouthaina

2015-01-01

Purpose: Outcomes for patients with diffuse large B-cell lymphoma (DLBCL) differ according to the site of presentation. With effective chemotherapy, the need for consolidative radiation therapy (RT) is controversial. We investigated the influence of primary bone presentation and receipt of consolidative RT on progression-free survival (PFS) and overall survival (OS) in patients with DLBCL. Methods and Materials: We identified 102 patients with primary bone DLBCL treated consecutively from 1988 through 2013 and extracted clinical, pathologic, and treatment characteristics from the medical records. Survival outcomes were calculated by the Kaplan-Meier method, with factors affecting survival determined by log-rank tests. Univariate and multivariate analyses were done with a Cox regression model. Results: The median age was 55 years (range, 16-87 years). The most common site of presentation was in the long bones. Sixty-five patients (63%) received R-CHOP–based chemotherapy, and 74 (72%) received rituximab. RT was given to 67 patients (66%), 47 with stage I to II and 20 with stage III to IV disease. The median RT dose was 44 Gy (range, 24.5-50 Gy). At a median follow-up time of 82 months, the 5-year PFS and OS rates were 80% and 82%, respectively. Receipt of RT was associated with improved 5-year PFS (88% RT vs 63% no RT, P=.0069) and OS (91% vs 68%, P=.0064). On multivariate analysis, the addition of RT significantly improved PFS (hazard ratio [HR] = 0.14, P=.014) with a trend toward an OS benefit (HR=0.30, P=.053). No significant difference in PFS or OS was found between patients treated with 30 to 35 Gy versus ≥36 Gy (P=.71 PFS and P=.31 OS). Conclusion: Patients with primary bone lymphoma treated with standard chemotherapy followed by RT can have excellent outcomes. The use of consolidative RT was associated with significant benefits in both PFS and OS

A polymorphism of EGFR extracellular domain is associated with progression free-survival in metastatic colorectal cancer patients receiving cetuximab-based treatment

International Nuclear Information System (INIS)

Gonçalves, Anthony; Turrini, Olivier; Lelong, Bernard; Viens, Patrice; Borg, Jean-Paul; Birnbaum, Daniel; Olschwang, Sylviane; Viret, Frédéric; Esteyries, Séverine; Taylor-Smedra, Brynn; Lagarde, Arnaud; Ayadi, Mounay; Monges, Geneviève; Bertucci, François; Esterni, Benjamin; Delpero, Jean-Robert

2008-01-01

Cetuximab, a monoclonal antibody targeting Epidermal Growth Factor Receptor (EGFR), is currently used in metastatic colorectal cancer (mCRC), but predictive factors for therapeutic response are lacking. Mutational status of KRAS and EGFR, and EGFR copy number are potential determinants of cetuximab activity. We analyzed tumor tissues from 32 EGFR-positive mCRC patients receiving cetuximab/irinotecan combination and evaluable for treatment response. EGFR copy number was quantified by fluorescence in situ hybridization (FISH). KRAS exon 1 and EGFR exons coding for extracellular regions were sequenced. Nine patients experienced an objective response (partial response) and 23 were considered as nonresponders (12 with stable disease and 11 with progressive disease). There was no EGFR amplification found, but high polysomy was noted in 2 patients, both of which were cetuximab responders. No EGFR mutations were found but a variant of exon 13 (R521K) was observed in 12 patients, 11 of which achieved objective response or stable disease. Progression-free and overall survivals were significantly better in patients with this EGFR exon 13 variant. KRAS mutations were found in 14 cases. While there was a trend for an increased KRAS mutation frequency in nonresponder patients (12 mutations out of 23, 52%) as compared to responder patients (2 out of 9, 22%), authentic tumor response or long-term disease stabilization was found in KRAS mutated patients. This preliminary study suggests that: an increase in EGFR copy number may be associated with cetuximab response but is a rare event in CRC, KRAS mutations are associated with low response rate but do not preclude any cetuximab-based combination efficacy and EGFR exon 13 variant (R521K) may predict for cetuximab benefit

Telomere shortening and survival in free-living corvids

NARCIS (Netherlands)

Salomons, H.M.; Mulder, G.A.; Zande, L. van de; Haussmann, M.F.; Linskens, M.H.K.; Verhulst, S.

2009-01-01

Evidence accumulates that telomere shortening reflects lifestyle and predicts remaining lifespan, but little is known of telomere dynamics and their relation to survival under natural conditions. We present longitudinal telomere data in free-living jackdaws (Corvus monedula) and test hypotheses on

Multicenter Phase II Study with Weekly Bendamustine and Paclitaxel as First- or Later-Line Therapy in Patients with Metastatic Breast Cancer: RiTa II Trial.

Science.gov (United States)

Loibl, Sibylle; Doering, Gabriele; Müller, Lothar; Grote-Metke, Albert; Müller, Roberto; Tomé, Oliver; Wiest, Wolfgang; Maisch, Andrea; Nekljudova, Valentina; von Minckwitz, Gunter

2011-12-01

The combination of bendamustine (B) and paclitaxel (P) as anthracycline-free treatment option in patients with advanced breast cancer has been evaluated in the previous RiTa I trial. The regimen of weekly B 70 mg/m(2) and P 90 mg/m(2) with a pause every 4th week was established as an effective regimen with low toxicity. The aim of the present RiTa II study was to investigate the potential of BP as anthracycline-free combination therapy. The primary objective was to determine the progression-free survival (PFS); secondary endpoints were safety, tolerability, overall response rate (ORR) and overall survival (OS). 26 patients were available, 15 received BP as first-line, 11 as beyond first-line treatment. 27% patients had triple-negative breast cancer (TNBC). Median PFS and OS were 7.3 months (95% confidence interval (CI): 5.5-10.9) and 14.9 months (95% CI: 9.9-22.9), respectively. The 1-year PFS rate was 20.3% and the 1-year OS rate 71.2%. The ORR was 42.3%, including 4 complete and 7 partial remissions. TNBC patients reached an ORR of 71.4%. Anthracycline-pretreated patients showed an ORR of 43.8%, confirming bendamustine's lack of cross-resistance to anthracycline agents. BP represents a favorable option with moderate toxicity in pretreated metastatic breast cancer and offers a possibility for application in anthracycline-pretreated and TNBC patients.

The prognostic value of family history among patients with urinary bladder cancer.

Science.gov (United States)

Egbers, Lieke; Grotenhuis, Anne J; Aben, Katja K; Alfred Witjes, J; Kiemeney, Lambertus A; Vermeulen, Sita H

2015-03-01

A history of urinary bladder cancer (UBC) in first-degree relatives increases UBC risk by twofold. The influence of positive family history on UBC prognosis is unknown. Here, we investigated association of first-degree UBC family history with clinicopathological characteristics and prognosis of UBC patients. Detailed clinical data of 1,465 non-muscle-invasive bladder cancer (NMIBC) and 250 muscle-invasive or metastatic bladder cancer (MIBC) patients, diagnosed from 1995 to 2010, were collected through medical file review. Competing risk analyses were used to compare recurrence-free survival (RFS) and progression-free survival (PFS) of NMIBC patients according to self-reported UBC family history. Overall survival in MIBC patients was estimated using Kaplan-Meier analysis. The added value of family history in prediction of NMIBC prognosis was quantified with Harrell's concordance-index. Hundred (6.8%) NMIBC and 14 (5.6%) MIBC patients reported UBC in first-degree relatives. Positive family history was statistically significantly associated with smaller tumor size and non-significantly with more favorable distribution of other tumor characteristics. In univariable analyses, positive family history correlated with longer RFS (p = 0.11) and PFS (p = 0.04). Hazard ratios for positive vs. negative family history after adjustment for clinicopathological characteristics were 0.75 (95% CI = 0.53-1.07) and 0.45 (95% CI = 0.18-1.12) for RFS and PFS, respectively. Five familial and 48 sporadic MIBC patients (Kaplan-Meier 10-year risk: 41% and 25%) died within 10 years. Family history did not improve the c-index of prediction models. This study shows that a first-degree family history of UBC is not clearly associated with NMIBC prognosis. Family history does not aid in prediction of NMIBC recurrence or progression. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.

Lapatinib or Trastuzumab Plus Taxane Therapy for Human Epidermal Growth Factor Receptor 2-Positive Advanced Breast Cancer: Final Results of NCIC CTG MA.31.

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Gelmon, Karen A; Boyle, Frances M; Kaufman, Bella; Huntsman, David G; Manikhas, Alexey; Di Leo, Angelo; Martin, Miguel; Schwartzberg, Lee S; Lemieux, Julie; Aparicio, Samuel; Shepherd, Lois E; Dent, Susan; Ellard, Susan L; Tonkin, Katia; Pritchard, Kathleen I; Whelan, Timothy J; Nomikos, Dora; Nusch, Arnd; Coleman, Robert E; Mukai, Hirofumi; Tjulandin, Sergei; Khasanov, Rustem; Rizel, Shulamith; Connor, Anne P; Santillana, Sergio L; Chapman, Judith-Anne W; Parulekar, Wendy R

2015-05-10

The efficacy of lapatinib versus trastuzumab combined with taxanes in the first-line setting of human epidermal growth factor receptor 2 (HER2) -positive metastatic breast cancer (BC) is unknown. The MA.31 trial compared a combination of first-line anti-HER2 therapy (lapatinib or trastuzumab) and taxane therapy for 24 weeks, followed by the same anti-HER2 monotherapy until progression. Stratification was by prior (neo)adjuvant anti-HER2 therapy, prior (neo)adjuvant taxane, planned taxane, and liver metastases. The primary end point was intention-to-treat (ITT) progression-free survival (PFS), defined as time from random assignment to progression by RECIST (version 1.0) criteria, or death for patients with locally assessed HER2-positive tumors. The primary test statistic was a stratified log-rank test for noninferiority. PFS was also assessed for patients with centrally confirmed HER2-positive tumors. From July 17, 2008, to December 1, 2011, 652 patients were accrued from 21 countries, resulting in 537 patients with centrally confirmed HER2-positive tumors. Median follow-up was 21.5 months. Median ITT PFS was 9.0 months with lapatinib and 11.3 months with trastuzumab. By ITT analysis, PFS was inferior for lapatinib compared with trastuzumab, with a stratified hazard ratio (HR) of 1.37 (95% CI, 1.13 to 1.65; P = .001). In patients with centrally confirmed HER2-positive tumors, median PFS was 9.1 months with lapatinib and 13.6 months with trastuzumab (HR, 1.48; 95% CI, 1.20 to 1.83; P < .001). More grade 3 or 4 diarrhea and rash were observed with lapatinib (P < .001). PFS results were supported by the secondary end point of overall survival, with an ITT HR of 1.28 (95% CI, 0.95 to 1.72; P = .11); in patients with centrally confirmed HER2-positive tumors, the HR was 1.47 (95% CI, 1.03 to 2.09; P = .03). As first-line therapy for HER2-positive metastatic BC, lapatinib combined with taxane was associated with shorter PFS and more toxicity compared with trastuzumab

Use of common analgesic medications and ovarian cancer survival

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Dixon, Suzanne C; Nagle, Christina M; Wentzensen, Nicolas

2017-01-01

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with improved survival in some cancers, but evidence for ovarian cancer is limited. METHODS: Pooling individual-level data from 12 Ovarian Cancer Association Consortium studies, we evaluated the association between self......-reported, pre-diagnosis use of common analgesics and overall/progression-free/disease-specific survival among 7694 women with invasive epithelial ovarian cancer (4273 deaths). RESULTS: Regular analgesic use (at least once per week) was not associated with overall survival (pooled hazard ratios, pHRs (95......% confidence intervals): aspirin 0.96 (0.88-1.04); non-aspirin NSAIDs 0.97 (0.89-1.05); acetaminophen 1.01 (0.93-1.10)), nor with progression-free/disease-specific survival. There was however a survival advantage for users of any NSAIDs in studies clearly defining non-use as less than once per week (pHR=0...

Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence

Energy Technology Data Exchange (ETDEWEB)

Campana, Davide; Nori, Francesca; Cacciari, Giulia; Tomassetti, Paola [University of Bologna, Department of Medical and Surgical Sciences, Bologna (Italy); Capurso, Gabriele; Panzuto, Francesco; Delle Fave, Gianfranco [University of Rome, Digestive and Liver Disease Unit, Rome (Italy); Partelli, Stefano [Sacro Cuore Don Calabria Hospital, Department of Surgery, Negrar (Italy); University of Verona, Department of Surgery, Verona (Italy); Universita Politecnica delle Marche, Pancreas Surgical Unit, Ancona (Italy); Tamburrino, Domenico; Falconi, Massimo [University of Verona, Department of Surgery, Verona (Italy); Universita Politecnica delle Marche, Pancreas Surgical Unit, Ancona (Italy)

2013-08-15

Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment modality for patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs). The aim of this study was to determine the time to progression of patients treated with PRRT and to identify the prognostic factors related to treatment response. Patients with sporadic GEP NETs prospectively treated with PRRT were retrospectively analysed. The primary end point was progression-free survival (PFS). A total of 69 patients (37 men and 32 women; 45 with pancreatic and 24 with gastrointestinal lesion; 22 NET G1 and 41 NET G2) were treated with {sup 90}Y or {sup 177}Lu. The objective response rate was 27.5 % (partial response, PR), while 50.7 % had stable disease and 23.2 % had progressive disease. Significant differences in PFS were observed in relationship to the stage of the disease (44 months for stage III, 23 months for stage IV), the evidence of a PR 6 months after the end of the PRRT (39 months in patients with a PR, 22 months in patients without a PR) and previous transarterial chemoembolization (TACE, yes 13 months vs no 31 months). Stage IV, NET G2 and previous TACE were found to be significant factors for tumour progression at multivariate analysis. Low tumour burden and a low proliferation index represent independent prognostic factors for long PFS, while previous chemoembolization techniques represent independent prognostic factors for early tumour progression and shorter PFS. Our data suggest that chemoembolization techniques to reduce the hepatic tumour burden should be avoided. (orig.)

PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients

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Im, Seock-Ah; Masuda, Norikazu; Im, Young-Hyuck; Inoue, Kenichi; Rai, Yoshiaki; Nakamura, Rikiya; Kim, Jee Hyun; Hoffman, Justin T.; Zhang, Ke; Giorgetti, Carla; Iyer, Shrividya; Schnell, Patrick T.; Bartlett, Cynthia Huang; Ro, Jungsil

2017-01-01

Purpose To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy–resistant metastatic breast cancer. Patients and Methods The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3) trial, a double-blind phase III study, included 521 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs) were assessed on study treatment and at the end of treatment. Results This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71) or placebo plus fulvestrant (n = 31). Palbociclib plus fulvestrant improved progression-free survival (PFS) compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached) but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065). The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92%) and leukopenia (29%); febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. Conclusion This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study. PMID:28831437

PALOMA-3: Phase III Trial of Fulvestrant With or Without Palbociclib in Premenopausal and Postmenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Metastatic Breast Cancer That Progressed on Prior Endocrine Therapy—Safety and Efficacy in Asian Patients

Directory of Open Access Journals (Sweden)

Hiroji Iwata

2017-08-01

Full Text Available Purpose: To assess efficacy and safety of palbociclib plus fulvestrant in Asians with endocrine therapy–resistant metastatic breast cancer. Patients and Methods: The Palbociclib Ongoing Trials in the Management of Breast Cancer 3 (PALOMA-3 trial, a double-blind phase III study, included 521 patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative metastatic breast cancer with disease progression on endocrine therapy. Patient-reported outcomes (PROs were assessed on study treatment and at the end of treatment. Results: This preplanned subgroup analysis of the PALOMA-3 study included premenopausal and postmenopausal Asians taking palbociclib plus fulvestrant (n = 71 or placebo plus fulvestrant (n = 31. Palbociclib plus fulvestrant improved progression-free survival (PFS compared with fulvestrant alone. Median PFS was not reached with palbociclib plus fulvestrant (95% CI, 9.2 months to not reached but was 5.8 months with placebo plus fulvestrant (95% CI, 3.5 to 9.2 months; hazard ratio, 0.485; 95% CI, 0.270 to 0.869; P = .0065. The most common all-cause grade 3 or 4 adverse events in the palbociclib arm were neutropenia (92% and leukopenia (29%; febrile neutropenia occurred in 4.1% of patients. Within-patient mean trough concentration comparisons across subgroups indicated similar palbociclib exposure between Asians and non-Asians. Global quality of life was maintained; no statistically significant changes from baseline were observed for patient-reported outcome scores with palbociclib plus fulvestrant. Conclusion: This is the first report, to our knowledge, showing that palbociclib plus fulvestrant improves PFS in asian patients. Palbociclib plus fulvestrant was well tolerated in this study.

Apatinib plus icotinib in treating advanced non-small cell lung cancer after icotinib treatment failure: a retrospective study.

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Xu, Jianping; Liu, Xiaoyan; Yang, Sheng; Zhang, Xiangru; Shi, Yuankai

2017-01-01

Treatment failure frequently occurs in patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who respond to EGFR tyrosine kinase inhibitors initially. This retrospective study tried to investigate the efficacy and safety of apatinib plus icotinib in patients with advanced NSCLC after icotinib treatment failure. This study comprised 27 patients with advanced NSCLC who had progressed after icotinib monotherapy. Initially, patients received oral icotinib (125 mg, tid) alone. When the disease progressed, they received icotinib plus apatinib (500 mg, qd, orally). Treatment was continued until disease progression, unacceptable toxicity or consent withdrawal. Followed up to December 2016, the median time of combined therapy was 7.47 months, and eight of 27 patients were dead. The median overall survival was not reached, and median progression-free survival (PFS) was 5.33 months (95% CI, 3.63-7.03 months). Moreover, the objective response rate (ORR) was 11.1%, and the disease control rate (DCR) was 81.5%. A total of 14 patients received combined therapy as the second-line treatment, and the ORR and DCR were 7.1% and 78.6%, respectively; 13 patients received drugs as the third- or later-line treatment, with an ORR and a DCR of 15.4% and 84.6%, respectively. In addition, 11 patients experienced icotinib monotherapy failure within 6 months with median PFS of 7.37 months, and 16 patients had progression after 6 months with median PFS of 2.60 months. The common drug-related toxic effects were hypertension (44.4%) and fatigue (37.0%). Apatinib plus icotinib is efficacious in treating patients with advanced NSCLC after icotinib treatment failure, with acceptable toxic effects.

No survival benefit from adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first-line treatment of metastatic colorectal cancer in KRAS wild type patients: a meta-analysis.

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Si-wei Zhou

Full Text Available The efficacy of combined therapies of oxaliplatin-based chemotherapy and anti-epidermal growth factor receptor (anti-EGFR monoclonal antibodies (MAbs remains controversial in colorectal cancer (CRC. The aim of this study is to estimate the efficacy and safety of adding cetuximab or panitumumab to oxaliplatin-based chemotherapy in the first line treatment in KRAS wild type patients with metastatic colorectal cancer (mCRC through meta-analysis.Medline, EMBASE, and Cochrane library, American Society of Clinical Oncology (ASCO and European Society for Medical Oncology (ESMO were searched. Eligible studies were randomized controlled trials (RCTs which evaluated oxaliplatin-based chemotherapy with or without anti-EGFR drugs (cetuximab or panitumumab in untreated KRAS wild type patients with mCRC. The outcomes included overall survival (OS, progression-free survival (PFS, overall response rate (ORR and toxicities. Hazard ratios (HR and risk ratio (RR were used for the meta-analysis and were expressed with 95% confidence intervals.This meta-analysis included four RCTs with 1270 patients, and all of the patients were administered oxaliplatin-based chemotherapy regimens with or without anti-EGFR MAbs. The result of heterogeneity of OS was not significant. Compared with chemotherapy alone, the addition of cetuximab or panitumumab didn't result in significant improvement in OS (HR = 1.00, 95%CI [0.88, 1.13], P = 0.95 or PFS (HR = 0.86, 95%CI [0.71, 1.04], P = 0.13. The subgroup analysis of cetuximab also revealed no significant benefit in OS (HR = 1.02, 95%CI [0.89, 1.18], P = 0.75 or in PFS (HR = 0.87, 95%CI [0.65, 1.17], P = 0.36. Patients who received combined therapy didn't have a higher ORR (Risk Ratio = 1.08, 95%CI [0.86, 1.36]. Toxicities slightly increased in anti-EGFR drugs group.The addition of cetuximab or panitumumab to oxaliplatin-based chemotherapy in first-line treatment of mCRC in wild type KRAS population did not improve efficacy in

Costo Efectividad del Tratamiento de Tumores Neuroendócrinos Pancreáticos Avanzados no Operables con Sunitinib en México.

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Muciño Ortega, Emilio; Chi-Chan, Alfredo; Peniche-Otero, Gustavo; Gutiérrez-Colín, Consuelo I; Herrera-Rojas, Joaquín; Galindo-Suárez, Rosa María

2012-12-01

Sunitinib had showed a substantial clinical benefit in patients with non-resectable pancreatic Neuroendocrine Tumors (NET). The objective of this study was to estimate the cost-effectiveness of sunitinib in the treatment of non-resectable pancreatic NET, from the perspective of the Social Security Mexican Institute (IMSS). A Markov model (2-week cycles) was used to estimate the health and economic consequences of sunitinib 37.5mg/day+best supportive care (BSC) regarding placebo+BSC (ten-years horizon, discount rate: 5%). Effectiveness measures were: overall survival (OS), progression-free survival (PFS) and quality adjusted life years (QALY). Resource utilization (BSC, adverse events management, medical follow-up) was estimated through a survey with Mexican oncologists (n=10). Unit costs of medication and medical resources were obtained from institutional sources. Sensitivity analyses were performed and acceptability curves were constructed. Sunitinib+BSC gained 0.49 years (PFS), 1.18 years (OS) and 0.70 QALY against placebo+BSC. Sunitinib+BSC increased medical direct costs (2011 US$) per patient in $20,854, which was driven by acquisition costs of sunitinib and medical follow up before progression. ICER's were $42,157, $17,662 and $29,808 per progression-free year, life-year and QALY gained, respectively, which remained robust through±25% changes in main parameters. At willingness to pay higher than $40,000, $22,400 and $37,600 sunitinib+BSC becomes the most cost-effective alternative in regards to PFS, OS and QALYs, respectively. At IMSS, sunitinib+BSC would provide substantial clinical benefits to patients suffering unresectable pancreatic NET, although the latter would increase medical costs of treatment and clinical follow up. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Assessment of Correlation Between Early and Late Efficacy Endpoints to Identify Potential Surrogacy Relationships in Non-Hodgkin Lymphoma: a Literature-Based Meta-analysis of 108 Phase II and Phase III Studies.

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Zhu, Rui; Lu, Dan; Chu, Yu-Waye; Chai, Akiko; Green, Michelle; Zhang, Nancy; Jin, Jin Yan

2017-05-01

Correlations between early and late efficacy endpoints were assessed to identify potential surrogate endpoints for overall survival (OS) or progression-free survival (PFS) with clinical trial-level data in three non-Hodgkin lymphoma (NHL) subtypes: diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). One hundred and eight phase II-III trials (129 trial arms) in DLBCL, FL, and MCL were identified and included in the database. Correlations between efficacy endpoints were analyzed using weighted linear regression and Pearson's coefficient of determination (R 2 ). In newly diagnosed DLBCL, 6-month PFS was strongly correlated with 2-year OS (R 2  = 0.81, 95% confidence interval [CI] 0.51-0.96). Six-month PFS was strongly correlated with 3-year PFS (R 2  = 0.89, 95% CI 0.62-0.96) in FL and was moderately correlated with 2-year OS (R 2  = 0.69, 95% CI 0.40-0.91) in MCL trials. Linear regression determined that a 10% increase in 6-month PFS would yield a 13% ± 1.2% increase in 2-year OS in DLBCL, a 23% ± 1.1% increase in 3-year PFS in FL, or a 6.7% ± 1.0% increase in 2-year OS in MCL. Both 6-month PFS and complete response (CR) rate were moderately correlated with median PFS in FL trials with R 2  = 0.66 (95% CI 0.52-0.98) and R 2  = 0.69 (95% CI 0.22-0.89), respectively. Six-month PFS is a potential surrogate endpoint for 2-year OS in newly diagnosed DLBCL and MCL and for 3-year PFS in FL. Both 6-month PFS and CR rate are potential surrogate endpoints for median PFS in FL patients. Confirmation and validation of these correlations may facilitate early interpretation of NHL trials.

Cell cycle and aging, morphogenesis, and response to stimuli genes are individualized biomarkers of glioblastoma progression and survival

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Southey Bruce R

2011-06-01

Full Text Available Abstract Background Glioblastoma is a complex multifactorial disorder that has swift and devastating consequences. Few genes have been consistently identified as prognostic biomarkers of glioblastoma survival. The goal of this study was to identify general and clinical-dependent biomarker genes and biological processes of three complementary events: lifetime, overall and progression-free glioblastoma survival. Methods A novel analytical strategy was developed to identify general associations between the biomarkers and glioblastoma, and associations that depend on cohort groups, such as race, gender, and therapy. Gene network inference, cross-validation and functional analyses further supported the identified biomarkers. Results A total of 61, 47 and 60 gene expression profiles were significantly associated with lifetime, overall, and progression-free survival, respectively. The vast majority of these genes have been previously reported to be associated with glioblastoma (35, 24, and 35 genes, respectively or with other cancers (10, 19, and 15 genes, respectively and the rest (16, 4, and 10 genes, respectively are novel associations. Pik3r1, E2f3, Akr1c3, Csf1, Jag2, Plcg1, Rpl37a, Sod2, Topors, Hras, Mdm2, Camk2g, Fstl1, Il13ra1, Mtap and Tp53 were associated with multiple survival events. Most genes (from 90 to 96% were associated with survival in a general or cohort-independent manner and thus the same trend is observed across all clinical levels studied. The most extreme associations between profiles and survival were observed for Syne1, Pdcd4, Ighg1, Tgfa, Pla2g7, and Paics. Several genes were found to have a cohort-dependent association with survival and these associations are the basis for individualized prognostic and gene-based therapies. C2, Egfr, Prkcb, Igf2bp3, and Gdf10 had gender-dependent associations; Sox10, Rps20, Rab31, and Vav3 had race-dependent associations; Chi3l1, Prkcb, Polr2d, and Apool had therapy-dependent associations

[The therapeutic value and safety of icotinib as first-line therapy for advanced non-small cell lung cancer patients].

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Chen, H; Wang, H P; Zhang, L; Si, X Y

2017-01-01

Objective: To evaluate the safety and efficacy of icotinib as first-line therapy in Chinese non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) sensitive mutations. Methods: Patients with stage ⅢB/Ⅳ NSCLC who had EGFR sensitive mutation and had no previous treatment were enrolled into this study. The response rates, progress free survival (PFS), overall survival (OS), and the safety were analyzed. Results: Ninety advanced adenocarcinoma patients were enrolled in this study, 44 patients had partial response (PR), 42 patients had stable disease (SD), 4 patients had progressive disease (PD), with an overall response rate (ORR) of 48.9%, and a disease control rate (DCR) of 95.6%. The median PFS was 14.9 months (95% CI 13.5-16.3) and the OS was 37.0 weeks (95% CI 27.9-46.1). Patients with brain metastases showed higher ORR( P =0.049). Patients with stage ⅢB had longer PFS than those with stage Ⅳ( P =0.007). The most common adverse events were grade 1-2 skin rash (38 patients, 40.9%). Other adverse events included dry skin, oral mucositis, diarrhea and liver function injury. Three patients withdrew because of severe liver injury or skin rash. No treatment related mortality occurred. Conclusions: Icotinib is effective and safe as first-line treatment for Chinese advanced NSCLC patients with EGFR sensitive mutation.

Gemcitabine, dexamethasone, and cisplatin (GDP) as salvage chemotherapy for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified.

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Qi, Fei; Dong, Mei; He, Xiaohui; Li, Yexiong; Wang, Weihu; Liu, Peng; Yang, Jianliang; Gui, Lin; Zhang, Changgong; Yang, Sheng; Zhou, Shengyu; Shi, Yuankai

2017-02-01

Standard therapeutic options for patients with relapsed or refractory peripheral T cell lymphoma-not otherwise specified (PTCL-NOS) remain unclear. There are few large cohort studies specifically focused on gemcitabine-based chemotherapy for PTCL-NOS. We retrospectively reviewed patients with relapsed or refractory PTCL-NOS who received salvage GDP (gemcitabine, dexamethasone, and cisplatin) chemotherapy at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China, from May 2008 to August 2014. Twenty-five patients were enrolled and analyzed. The median number of cycles of GDP chemotherapy per patient was four (range, 2-8 cycles). Overall response rate was 64.0% (16/25) with five achieved complete remission or complete remission unconfirmed. After a median follow-up of 9 months, median overall survival (OS) and progression-free survival after relapse or progression (second-PFS) were 9.3 and 5.4 months. One-year PFS rate and 1-year OS rate were 27.4% and 43.9%, respectively. Median second-PFS was significantly longer in patients sensitive to GDP than the ones resistant to the treatment (10.3 vs. 2.8 months, p GDP including neutropenia (8/25), thrombocytopenia (5/25), and anemia (4/25). Taken together, our study suggests that GDP is an effective and optional salvage regimen for relapsed or refractory PTCL-NOS.

Five-year outcomes for frontline brentuximab vedotin with CHP for CD30-expressing peripheral T-cell lymphomas.

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Fanale, Michelle A; Horwitz, Steven M; Forero-Torres, Andres; Bartlett, Nancy L; Advani, Ranjana H; Pro, Barbara; Chen, Robert W; Davies, Andrew; Illidge, Tim; Uttarwar, Mayur; Lee, Shih-Yuan; Ren, Hong; Kennedy, Dana A; Shustov, Andrei R

2018-05-10

This phase 1 study evaluated frontline brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone (BV+CHP; 6 cycles, then up to 10 cycles of brentuximab vedotin monotherapy) in 26 patients with CD30 + peripheral T-cell lymphoma, including 19 with systemic anaplastic large cell lymphoma. All patients (100%) achieved an objective response, with a complete remission (CR) rate of 92%; none received a consolidative stem cell transplant. After a median observation period of 59.6 months (range, 4.6-66.0) from first dose, neither the median progression-free survival (PFS) nor the median overall survival (OS) was reached. No progression or death was observed beyond 35 months. The estimated 5-year PFS and OS rates were 52% and 80%, respectively. Eighteen of 19 patients (95%) with treatment-emergent peripheral neuropathy (PN) reported resolution or improvement of symptoms. Thirteen patients (50%) remained in remission at the end of the study, with PFS ranging from 37.8+ to 66.0+ months. Eight of these 13 patients received the maximum 16 cycles of study treatment. These final results demonstrate durable remissions in 50% of patients treated with frontline BV+CHP, suggesting a potentially curative treatment option for some patients. This trial was registered at www.clinicaltrials.gov as #NCT01309789. © 2018 by The American Society of Hematology.

Option A Improved HIV-free Infant Survival and Mother to Child HIV Transmission at 9–18 Months in Zimbabwe

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BUZDUGAN, Raluca; KANG DUFOUR, Mi-Suk; MCCOY, Sandra I; WATADZAUSHE, Constancia; DIRAWO, Jeffrey; MUSHAVI, Angela; MUJURU, Hilda Angela; MAHOMVA, Agnes; KANGWENDE, Rugare Abigail; HAKOBYAN, Anna; MUGURUNGI, Owen; COWAN, Frances M; PADIAN, Nancy S

2016-01-01

Objective We evaluated the impact of Option A on HIV-free infant survival and mother-to-child transmission (MTCT) in Zimbabwe. Design Serial cross-sectional community-based serosurveys. Methods We analyzed serosurvey data collected in 2012 and 2014 among mother-infant pairs from catchment areas (CAs) of 132 health facilities from 5 of 10 provinces in Zimbabwe. Eligible infants (alive or deceased) were born 9–18 months before each survey to mothers ≥16 years old. We randomly selected mother-infant pairs and conducted questionnaires, verbal autopsies and collected blood samples. We estimated: 1) the HIV-free infant survival and MTCT rate within each CA and compared the 2012 and 2014 estimates using a paired t-test, 2) number of HIV infections averted due to the intervention. Results We analyzed 7,249 mother-infant pairs with viable maternal specimens collected in 2012 and 8,551 in 2014. The mean difference in the CA-level MTCT between 2014 and 2012 was −5.2 percentage points (95% confidence interval (CI)=−8.1, −2.3, pOption A regimen. The association between HIV-free infant survival and duration of Option A implementation was not significant at the multivariate level (p=0.093). Conclusions We found a substantial and statistically significant increase in HIV-free survival and decrease in MTCT among infants aged 9–18 months following Option A rollout in Zimbabwe. This is the only impact evaluation of Option A and shows the effectiveness of Option A and Zimbabwe’s remarkable progress towards eMTCT. PMID:27058354

Neoadjuvant chemotherapy by bronchial arterial infusion in patients with unresectable stage III squamous cell lung cancer.

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Zhu, Jun; Zhang, Hai-Ping; Jiang, Sen; Ni, Jian

2017-08-01

We investigated the effects of neoadjuvant chemotherapy administered via bronchial arterial infusion (BAI) on unresectable stage III lung squamous cell carcinoma (SCC). This was a single-arm retrospective study of chemotherapy with gemcitabine plus cisplatin (GP) administered via BAI to patients with unresectable lung SCC. Data regarding the post-treatment response rate, downstage rate, and surgery rate, as well as progression-free survival (PFS), overall survival (OS), quality of life, and post-BAI side effects were collected. A total of 36 patients were enrolled in this study between August 2010 and May 2014. The response rate was 72.2%, and the downstage rate was 22.2%. Among the patients who were downstaged, 16 (44.4%) patients were because of their T stage, and 5 (13.9%) patients were downstaged due to to their N stage. The surgery rate was 52.8%, the 1-year survival rate was 75.4%, and the 2-year survival rate was 52.1%. The median PFS was 14.0 months [95% confidence interval (CI): 8.6-19.4], and the median OS was 25.0 months (95% CI: 19.1-30.9). The quality of life was significantly improved, and the chemotherapy was well tolerated. Compared with intravenous neoadjuvant chemotherapy, BAI chemotherapy significantly improved the surgery rate, prolonged PFS and OS, and improved the quality of life in patients with unresectable stage III lung SCC.

A new inorganic-organic composite coagulant, consisting of polyferric sulphate (PFS) and polyacrylamide (PAA).

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Moussas, P A; Zouboulis, A I

2009-08-01

Currently, research is focused on the synthesis of new composite coagulants, which are constituted of both inorganic and organic materials. In this paper, the development of relevant reagents was investigated, by combining the inorganic pre-polymerised iron-based coagulant Polyferric Sulphate (PFS) with an organic, non-ionic polymer (Polyacrylamide, PAA) under different PAA/Fe (mg/l) and OH/Fe molar ratios. Moreover, the new reagents were characterised in terms of typical properties, stability and morphological analysis (XRD, FTIR, SEM). Their coagulation performance, when treating low or high turbid kaolin-humic acid suspensions, was also investigated, whereas the applied coagulation mechanisms were discussed by using the Photometric Dispersion Analysis (PDA) analysis. The results show that the new coagulation reagents present improved properties, including increased effective polymer species concentration, and they exhibit very good stability. The respective tests using PDA confirmed that the predominant coagulation mechanism of PFS-PAA is the bridge formation mechanism. Coagulation experiments in low or high turbid kaolin-humic acid suspensions reveal that the novel composite reagent PFS-PAA exhibits better coagulation performance, when compared with simple PFS, in terms of zeta-potential reduction, turbidity and organic matter removal and residual iron concentration.