Toni K Choueiri

Dana-Farber Cancer Institute, Boston, Massachusetts, United States

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Publications (253)1726.27 Total impact

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    ABSTRACT: Programmed death-1 (PD-1) receptor/PD-1 ligand (PD-L1) pathway negatively regulates T cell-mediated responses. The prognostic impact of PD-L1 expression needs to be defined in urothelial carcinoma (UC). Formalin-fixed paraffin embedded tumor samples from 160 patients with UC were retrieved. PD-L1 expression was evaluated by immunohistochemistry (IHC) using a mouse monoclonal anti-PD-L1 antibody (405.9A11). PD-L1 positivity on tumor cell membrane was defined as ≥5% of tumor cell membrane staining. The extent of tumor infiltrating mononuclear cells (TIMCs) as well as PD-L1 expression on TIMCs was scored from 0 to 4. A score of 2, 3, or 4 was considered PD-L1 positive. Clinico-pathological variables were documented. Cox regression model was used to assess the association of PD-L1 expression with overall survival (OS) in patients who developed metastases. TIMCs were present in 143 of the 160 patient samples. Out of 160 samples, 32 (20%) had positive PD-L1 expression in tumor cell membrane. Out of 143 samples with TIMCs, 58(40%) had positive PD-L1 expression in TIMC. Smoking history, prior BCG use and chromosome 9 loss did not correlate with PD-L1 expression in either tumor cell membrane or TIMCs. PD-L1 positivity was not different between non-invasive or invasive UC. In patients who developed metastases (M1) and were treated with systemic therapy (n=100), PD-L1 positivity on tumor cell membrane was seen in 14% of patients and did not correlate with OS (p=0.45). Out of 89 M1 patients who had evaluable PD-L1 on TIMCs, PD-L1 expression was seen in 33% of patients and was significantly associated with longer OS on multivariate analysis (p=0.0007). PD-L1 is widely expressed in tumor cell membrane and TIMCs in UC. PD-L1 in tumor cells was not predictive of OS. However, positive PD-L1 expression in TIMCs was significantly associated with longer survival in those patients who developed metastases. © The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Annals of oncology : official journal of the European Society for Medical Oncology / ESMO. 01/2015;
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    ABSTRACT: Ror2 is a Wnt ligand receptor that is overexpressed in a variety of tumors including clear cell renal cell carcinoma (ccRCC). Here we demonstrate that expression of wild type Ror2 results in increased tumorigenic properties in in vitro cell culture and in vivo xenograft models. In addition, Ror2 expression produced positive changes in both cell migration and invasion, which were dependent on matrix metalloprotease 2 (MMP2) activity. Mutations in key regions of the kinase domain of Ror2 resulted in the abrogation of increased tumor growth, cell migration, and cell invasion observed with expression of wild-type Ror2. Finally, we examined Ror2 expression as a prognostic biomarker for ccRCC utilizing the TCGA ccRCC dataset. High expression of Ror2 showed a significant correlation with higher clinical stage, nuclear grade, and tumor stage. Furthermore, high expression of Ror2 in ccRCC patients correlated with significant lower overall survival, cancer specific survival, and recurrence free survival. Together, these findings suggest that Ror2 plays a central role in influencing the ccRCC phenotype, and can be considered as a negative prognostic biomarker and potential therapeutic target in this cancer.
    PLoS ONE 12/2014; 9(12):e116101. · 3.53 Impact Factor
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    ABSTRACT: Purpose: The interaction of programmed death-1 ligand (PD-L1) with its receptor (PD-1) on T cells inactivates antitumor immune responses. PD-L1 expression has been associated with poor outcomes in renal cell carcinoma (RCC) but has not been investigated in advanced RCC patients receiving vascular endothelial growth factor (VEGF)-targeted therapy. Experimental Design: Formalin-fixed paraffin-embedded (specimens were collected at baseline from patients in the COMPARZ trial. Tumor cell PD-L1 expression by immunohistochemistry was evaluated using H-score (HS). Dual PD-L1/CD68 staining was used to differentiate PD-L1 tumor expression from tumor-associated macrophages. Intratumor CD8-positive T cells were quantified morphometrically. Associations between biomarkers and survival were investigated using the log-rank test. Results: HS data were available from 453 of 1110 patients. Sixty-four percent of patients had negative PD-L1 expression (HS=0). Patients with HS>55 (n=59, 13%) had significantly shorter overall survival (OS) than those with HS≤55 in both pazopanib and sunitinib arms (median 15.1 vs 35.6 and 15.3 vs 27.8 months, respectively, P=0.03). In both arms, median OS was shortest in patients with HS>55 and intratumor CD8-positive T-cell counts >300 (9.6 and 11.9 months with pazopanib and sunitinib, respectively). Median OS in patients with HS≤55 and CD8-positive T-cell counts ≤300 was 36.8 and 28.0 months with pazopanib and sunitinib, respectively. Progression-free survival results were similar to OS results. Conclusions: Increased tumor cell PD-L1, or PD-L1 plus tumor CD8-positive T-cell counts, were associated with shorter survival in metastatic RCC patients receiving VEGF-targeted agents. These findings may have implications for future design of randomized clinical trials in advanced RCC. Copyright © 2014, American Association for Cancer Research.
    Clinical Cancer Research 12/2014; · 8.19 Impact Factor
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    ABSTRACT: The etiologic heterogeneity of cancer has traditionally been investigated by comparing risk factor frequencies within candidate sub-types, defined for example by histology or by distinct tumor markers of interest. Increasingly tumors are being profiled for molecular features much more extensively. This greatly expands the opportunities for defining distinct sub-types. In this article we describe an exploratory analysis of the etiologic heterogeneity of clear cell kidney cancer. Data are available on the primary known risk factors for kidney cancer, while the tumors are characterized on a genome-wide basis using expression, methylation, copy number and mutational profiles. We use a novel clustering strategy to identify sub-types. This is accomplished independently for the expression, methylation and copy number profiles. The goals are to identify tumor sub-types that are etiologically distinct, to identify the risk factors that define specific sub-types, and to endeavor to characterize the key genes that appear to represent the principal features of the distinct sub-types. The analysis reveals strong evidence that gender represents an important factor that distinguishes disease sub-types. The sub-types defined using expression data and methylation data demonstrate considerable congruence and are also clearly correlated with mutations in important cancer genes. These sub-types are also strongly correlated with survival. The complexity of the data presents many analytical challenges including, prominently, the risk of false discovery. Genomic profiling of tumors offers the opportunity to identify etiologically distinct sub-types, paving the way for a more refined understanding of cancer etiology.
    BMC Medical Research Methodology 12/2014; 14(1):138. · 2.17 Impact Factor
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    ABSTRACT: A systematic review and meta-analysis was conducted to determine the relative risk (RR) of congestive heart failure (CHF) associated with approved multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Eligible studies included randomized trials comparing arms with and without an FDA-approved VEGFR TKI. Statistical analyses calculated the relative risk (RR) and 95% confidence intervals (CI). A total of 10,647 patients from 16 phase III trials and 5 phase II trials were selected. All grade CHF occurred in 138 of 5752 (2.39%) patients receiving VEGFR TKIs and 37 of 4895 (0.75%) patients in the non-TKI group. High-grade CHF occurred in 17 of 1426 (1.19%) patients receiving VEGFR TKIs and 8 of 1232 (0.65%) patients in the non-TKI group. The RR of all grade and high-grade CHF for the TKI vs. no TKI arms was 2.69 (p < 0.001; 95% CI: 1.86 to 3.87) and 1.65 (p = 0.227, 95% CI: 0.73 to 3.70), respectively. The RR of relatively specific TKIs (axitinib) was similar to relatively non-specific TKIs (sunitinib, sorafenib, vandetanib, pazopanib).
    Critical Reviews in Oncology/Hematology 12/2014; · 4.05 Impact Factor
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    ABSTRACT: It is unknown whether lymph node metastases (LNM) and their localization negatively affect clinical outcome in metastatic renal cell carcinoma (mRCC) patients. To evaluate the clinicopathological features, survival outcome, and treatment response in mRCC patients with LNM versus those without LNM after treatment with targeted therapies (TT). Patients (n=2996) were first analyzed without consideration of lymph node (LN) localization or histologic subtype. Additional analyses (n=1536) were performed in subgroups of patients with supradiaphragmatic (SPD) LNM, subdiaphragmatic (SBD) LNM, and patients with LNM in both locations (SPD+/SBD+) without histologic considerations, and then separately in clear cell RCC (ccRCC) and non-clear cell RCC (nccRCC) patients, respectively. The primary outcome was overall survival (OS) and the secondary outcome was progression-free survival (PFS). All patients with LNM had worse PFS (p=0.001) and OS (p<0.001) compared to those without LNM. Compared to patients without LNM (PFS 8.8 mo; OS 25.1 mo), any SBD LNM involvement was associated with worse PFS (SBD, 6.8 mo; p=0.003; SPD+/SBD+, 5.5 mo; p<0.001) and OS (SBD, 16.2 mo; p<0.001; SPD+/SBD+, 11.5 mo; p<0.001). Both SBD and SPD+/SBD+ LNM were retained as independent prognostic factors in multivariate analyses (MVA) for PFS (p=0.006 and p=0.022, respectively) and OS (both p<0.001), while SPD LNM was not an independent risk factor. Likewise, in ccRCC, SBD LNM (19.8 mo) and SPD+/SBD+ LNM (12.85 mo) patients had the worst OS. SPD+/SBD+ LNM (p=0.006) and SBD LNM (p=0.028) were independent prognostic factors for OS in MVA, while SPD LNM was not significant (p=0.301). The study is limited by its retrospective design and the lack of pathologic evaluation of LNM in all cases. The metastatic spread of RCC to SBD lymph nodes is associated with poor prognosis in mRCC patients treated with TT. The presence of lymph node metastases below the diaphragm is associated with shorter survival outcome when metastatic renal cell carcinoma (mRCC) patients are treated with targeted therapies. Clinical trials should evaluate whether surgical removal of regional lymph nodes at the time of nephrectomy may improve outcomes in high-risk RCC patients. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    European urology. 12/2014;
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    ABSTRACT: Objectives: Treating high-risk prostate cancer (CaP) with definitive therapy improves survival. We evaluated whether having health insurance reduces racial disparities in the use of definitive therapy for high-risk CaP. Materials and methods: The Surveillance, Epidemiology, and End Results Program was used to identify 70,006 men with localized high-risk CaP (prostate-specific antigen level 4 20 ng/ml or Gleason score 8–10 or stage 4 cT3a) diagnosed from 2007 to 2010. We used multivariable logistic regression to analyze the 64,277 patients with complete data to determine the factors associated with receipt of definitive therapy. Results: Compared with white men, African American (AA) men were significantly less likely to receive definitive treatment (adjusted odds ratio [AOR] ¼ 0.60; 95% CI: 0.56–0.64; P o 0.001) after adjusting for sociodemographics and known CaP prognostic factors. There was a significant interaction between race and insurance status (P interaction ¼ 0.01) such that insurance coverage was associated with a reduction in racial disparity between AA and white patients regarding receipt of definitive therapy. Specifically, the AOR for definitive treatment for AA vs. white was 0.38 (95% CI: 0.27–0.54, P o 0.001) among uninsured men, whereas the AOR was 0.62 (95% CI: 0.57–0.66, P o 0.001) among insured men. Conclusions: AA men with high-risk CaP were significantly less likely to receive potentially life-saving definitive treatment when compared with white men. Having health insurance was associated with a reduction in this racial treatment disparity, suggesting that expansion of health insurance coverage may help reduce racial disparities in the management of aggressive cancers. r
    Urologic Oncology 12/2014; 32(8):1285-1291. · 3.36 Impact Factor
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    ABSTRACT: A trial-level meta-analysis was conducted to determine the relative risk (RR) of pancreatitis associated with multi-targeted vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI). Eligible studies included randomized phase 2 and 3 trials comparing arms with and without an FDA-approved VEGFR TKI (sunitinib, sorafenib, pazopanib, axitinib, vandetanib, cabozantinib, ponatinib, regorafenib). Statistical analyses calculated the RR and 95% confidence intervals (CI). A total of 10,578 patients from 16 phase III trials and 6 phase II trials were selected. The RR for all grade and high-grade pancreatitis for the TKI vs. no TKI- arms was 1.95 (p=0.042, 95% CI: 1.02 to 3.70) and 1.89 (p=0.069, 95% CI: 0.95 to 373), respectively. No differential impact of malignancy type or specific TKI agent was seen on RR of all grade of high grade pancreatitis. Better patient selection and monitoring may mitigate the risk of severe pancreatitis. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Critical Reviews in Oncology/Hematology 12/2014; · 4.05 Impact Factor
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    ABSTRACT: The past several years have witnessed a resurgence of interest in cancer immunotherapy. The development of blocking antibodies against the inhibitory programmed death-1 (PD-1) pathway represents a clinical breakthrough in the treatment of solid tumors such as melanoma, and these agents show great promise in renal cell carcinoma (RCC). The early data have been surprising in that they demonstrate that blockade of a single immune checkpoint can elicit objective responses in patients with RCC, despite the recognized complexity of the immunosuppressive tumor microenvironment. Reinvigorating the patient's own immune cells to reactivate and to target the tumor has the potential advantages of more selective killing and thus decreased toxicity. In addition, checkpoint blockade immunotherapy has the advantage of inducing a memory response that is unattainable with our current cytotoxic and targeted therapies. This Crossroads overview will highlight the emerging investigation of PD-1 blockade in RCC and how this T cell-targeted strategy may thwart the tumor's escape mechanisms and shift the immune system/tumor balance back to a state of equilibrium and even to tumor elimination. Cancer Immunol Res; 2(12); 1132-41. ©2014 AACR. ©2014 American Association for Cancer Research.
    Cancer immunology research. 12/2014; 2(12):1132-1141.
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    ABSTRACT: Salvage systemic therapy for advanced urothelial carcinoma has substantial unmet needs. Small phase II trials have been conducted with varying eligibility criteria, which render cross-trials comparisons difficult. Moreover, accrual to trials is hampered by comorbidities, elderly age and poor performance status. Therefore, improvements in clinical trial design may facilitate further advances. This commentary summarizes recent data regarding prognostic factors, which allow us to recommend inclusive, yet rational, eligibility criteria and stratification factors to enhance accrual and improve interpretability of data from phase II trials: 1) allowing either prior perioperative platinum-based chemotherapy within 1 year or prior platinum-based chemotherapy for metastatic disease, 2) allowing ≤2 prior lines of therapy, 3) allow patients regardless of quality of response to prior therapy, 4) allow all sites of primary urothelial malignancy, and 5) a preplanned analysis of outcomes controlled for baseline prognostic factors.
    Clinical Genitourinary Cancer 12/2014; · 1.69 Impact Factor
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    ABSTRACT: Death within 1 month of surgery is considered treatment related and serves as an important healthcare quality metric. We sought to identify the incidence of and factors associated with 1-month mortality after cancer-directed surgery. We used the Surveillance, Epidemiology and End Results Program to study a cohort of 1,110,236 patients diagnosed from 2004-2011 with cancers that are among the 10 most common or most fatal who received cancer-directed surgery. Multivariable logistic regression analyses were used to identify factors associated with 1-month mortality after cancer-directed surgery. 53,498 patients (4.8%) died within 1 month of cancer-directed surgery. Patients who were married, insured, or who had a top 50th percentile income or educational status had lower odds of 1-month mortality from cancer-directed surgery ([adjusted odds ratio (AOR) 0.80; 95% CI 0.79 - 0.82; P<0.001], [AOR 0.88; (0.82 - 0.94); P<0.001], [AOR 0.95; (0.93 - 0.97); P<0.001], and [AOR 0.98; (0.96 - 0.99); P=0.043], respectively). Patients who were non-white minority, male, or older (per year increase), or who had advanced tumor stage 4 disease all had a higher risk of 1-month mortality after cancer-directed surgery, with AORs of 1.13 (1.11 - 1.15), P<0.001; 1.11 (1.08 - 1.13), P<0.001; 1.02 (1.02 - 1.03), P<0.001; and 1.89 (1.82 - 1.95), P<0.001 respectively. Unmarried, uninsured, non-white, male, older, less educated, and poorer patients were all at a significantly higher risk for death within 1 month of cancer-directed surgery. Efforts to reduce 1-month surgical mortality and eliminate sociodemographic disparities in this adverse outcome could significantly improve survival among patients with cancer. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
    Annals of Oncology 11/2014; · 6.58 Impact Factor
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    ABSTRACT: A trial-level meta-analysis of randomized phase II/III controlled trials (RCT) was conducted to determine the relative risk (RR) of hepatotoxicity associated with vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKI) approved by the U.S. FDA. Citations from PubMed/Medline, abstracts from major conferences, clinicaltrials.gov and manufacturer's package inserts were reviewed to include RCTs comparing arms with or without a VEGFR TKI. The RR of all-grade ALT, AST, ALP and bilirubin elevation in 18,282 patients from 52 trials was 1.57 (95% CI 1.38-1.79, p < 0.001), 1.57 (95% CI 1.36-1.81, p < 0.001), 1.20 (95% CI 1.09-1.83, p < 0.001) and 1.55 (95% CI 1.21-1.97, p < 0.001) respectively, and high-grade elevation was 1.66 (95% CI 1.25-2.20, p = 0.001), 1.61 (95% CI 1.21-2.14, p = 0.001), 1.02 (95% CI 0.70-1.47, p = 0.932) and 1.34 (95% CI 1.0-1.81, p = 0.054) respectively compared to those in the non-TKI group. However, the incidence of hepatic failure with VEGFR TKI was only 0.8%. Better post-marketing reporting may modify this calculated risk.
    Critical Reviews in Oncology/Hematology 11/2014; · 4.05 Impact Factor
  • Journal of Clinical Oncology 11/2014; · 17.88 Impact Factor
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    ABSTRACT: Adrenocortical cancer is a rare malignancy. While surgery is the cornerstone of the management of localized disease, metastatic disease is hard to treat. Cytotoxic chemotherapy and mitotane have been utilized with a variable degree of benefit and few long-term responses. A growing understanding of the molecular pathogenesis of this malignancy as well as multidisciplinary and multi-institutional collaborative efforts will result in better defined targets and subsequently, effective novel therapies.
    Critical Reviews in Oncology/Hematology 11/2014; · 4.05 Impact Factor
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    ABSTRACT: Taxanes such as paclitaxel and docetaxel are commonly employed for second or third-line salvage systemic therapy for metastatic urothelial carcinoma (UC). Although trials have generally excluded previous exposure to taxanes when employing a taxane in a salvage therapy trial, taxanes may not be completely cross-resistant. Hence, we aimed to study outcomes with docetaxel following prior paclitaxel and the reverse sequence to identify the level of cross-resistance between these taxanes.Patients and methodsData from a randomized phase II trial that compared salvage therapy with docetaxel combined with either placebo or vandetanib for advanced UC were analyzed. Both arms were combined for analysis since no differences in any outcomes were observed. Data were also requested from institutions for patients that received paclitaxel following prior docetaxel. Descriptive statistics were used to summarize patient and treatment characteristics as well as outcomes. The primary clinical endpoint of interest was OS.ResultsOf 148 patients that received docetaxel plus either vandetanib or placebo, 21 had received prior paclitaxel. No difference in OS, progression-free survival (PFS) and response rate was observed with docetaxel based on prior paclitaxel after adjusting for known prognostic factors. Among the 8 patients who received paclitaxel following prior docetaxel, partial response was observed in 1 patient (12.5%) and stable disease in 2 patients (25%).Conclusions Docetaxel after prior paclitaxel and the reverse sequence demonstrates activity in advanced UC. There is no strong evidence to disallow patients with prior exposure to a taxane to enroll into a clinical trial involving another taxane.
    Clinical Genitourinary Cancer 11/2014; · 1.69 Impact Factor
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    ABSTRACT: To assess contemporary characteristics, hospital admissions, charges, and mortality in patients with prostate cancer (CaP) who have bone metastases and skeletal-related events in an observational study.
    Urologic Oncology 10/2014; · 3.36 Impact Factor
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    ABSTRACT: Primary androgen deprivation therapy (pADT) is commonly used to treat elderly men diagnosed with localized prostate cancer (CaP), despite the lack of evidence supporting its use. To examine the effect of pADT on mortality and to assess contemporary trends of pADT use in elderly men with CaP. Men older than 65 yr residing in Surveillance, Epidemiology, and End Results (SEER) registry areas diagnosed with localized or locally advanced CaP between 1992 and 2009 and not receiving definitive therapy. Propensity score (PS)-weighted Cox proportional hazards models were used to estimate the effect of pADT use on overall survival among patients receiving pADT. The interaction between comorbidity-adjusted life expectancy (LE) and pADT use was assessed within the Cox and PS-weighted models. Contemporary (2004-2009) trends for pADT use were analyzed by linear regression. The primary cohort included 46 376 men, of whom 17 873 received pADT (39%). Patients with >10 yr LE had lower pADT utilization rates than patients with short LE. Between 2004 and 2009, the use of pADT in men with localized CaP decreased by 14% (from 36% to 22%). Relative to observation, pADT was associated with a survival disadvantage, with a hazard ratio for all-cause mortality of 1.37 (95% confidence interval 1.20-1.56). Limitations included biases not accounted for by the PS-weighted model, changes in CaP staging over the study period, the absence of prostate-specific antigen (PSA) data prior to 2004, and the limits of retrospective analysis to demonstrate causality. The use of pADT in elderly men with localized CaP has decreased over time. For men forgoing primary definitive therapy, the use of pADT is not associated with a survival benefit compared to observation, and denies men an opportunity for cure with definitive therapy. The deleterious effect of pADT is most pronounced in men with prolonged LE. In this report, we assessed the effect of primary androgen deprivation (pADT) on prostate cancer mortality and determined current trends in the use of pADT. We showed that use of pADT in men aged >65 yr with localized prostate cancer has decreased over time. We also found that pADT is detrimental to men with localized prostate cancer, and particularly men with longer life expectancy. Therefore, we conclude that ADT should not be used as a primary treatment for men with prostate cancer that has not spread beyond the prostate. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    European Urology 10/2014; · 12.48 Impact Factor
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    ABSTRACT: Definitive treatment of high-risk prostate cancer with radical prostatectomy or radiation improves survival. We assessed whether racial disparities in the receipt of definitive therapy for prostate cancer vary by regional income.
    Urologic oncology. 10/2014;
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    ABSTRACT: Background The complete remission (CR) rate with salvage systemic therapy for urothelial carcinoma (UC) is unclear and its value as an intermediate endpoint and association with survival are unknown. Materials and methods Data from Phase II trials of salvage chemotherapy and/or biologic agents were pooled. Data regarding response, overall survival (OS), progression-free survival (PFS), time from prior chemotherapy (TFPC), hemoglobin (Hb), performance status (PS) and liver metastasis (LM) status were collected. Cox proportional hazards regression was used to evaluate the association of CR and other prognostic factors with outcomes. Results 789 of 818 patients enrolled in 12 phase II trials were evaluable. CR and partial response (PR) were seen in 14 (1.8%) and 109 (13.8%) patients. Median (95% CI) OS for those with a CR was 21.5 (14.2-34.3) months, compared with 6.7 (6.0-7.0) months in those without a CR (p<0.001). Median (95% CI) PFS for those with a CR was 15.7 (8.2-27.1) months, compared with 2.6 (2.4-2.8) months for those without a CR (p<0.001). Prior cisplatin and TFPC ≥3 months were associated with CR (p<0.05). The presence of poor prognostic factors and suboptimal response to prior therapy did not preclude CR. Conclusions CR occurs in 1.8% of patients receiving salvage therapy for advanced UC, and is strongly associated with durable OS and PFS. CR warrants validation as an intermediate endpoint and may help select agents for further investigation and tumors for molecular interrogation.
    Clinical Genitourinary Cancer 10/2014; · 1.69 Impact Factor
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    ABSTRACT: Background Targeted therapies improve survival in metastatic renal cell carcinoma (mRCC). However, survival patterns can be divergent and patients at the two extremes of the survival spectrum need to be characterized. Patients and Methods Data from 2161 patients included in the International mRCC Database Consortium (IMDC) were analyzed. We identified patients based on their duration of survival. Long-term survivors (LTS) were defined as overall survival (OS) ≥ 4 years and short-term survivors (STS) were patients with OS ≤ 6 months from the start of targeted therapy. Baseline characteristics including demographic, clinico-pathologic, and laboratory data were compared between LTS and STS. Treatment response by the RECIST criteria was summarized for the two survival groups. Results 152 patients were LTS and 218 were STS. Adverse clinical and laboratory prognostic factors previously described in the IMDC prognostic model were significantly more frequent in the STS group (p<0.0001). In the LTS group, 138 patients (91%) had non-progressive disease (non-PD) as best response to first-line targeted therapy, and 56 of 94 patients (60%) who received second-line therapy had non-PD. In the STS group, only 51 patients (23%) had non-PD on first-line therapy. None of 21 the patients who received second-line therapy had non-PD as best response. In LTS, the median duration of therapy was 23.6 months (range: 0.4, 81.8+) for first-line and 11.5 months (range: 0.6-45.7) for second-line compared to 2.0 and 0.8 months for the STS respectively. Conclusion Baseline prognostic criteria and absence of PD after first and second-line targeted therapy may characterize long-term survivors.
    Clinical Genitourinary Cancer 10/2014; · 1.69 Impact Factor

Publication Stats

4k Citations
1,726.27 Total Impact Points

Institutions

  • 2008–2014
    • Dana-Farber Cancer Institute
      • • Department of Radiation Oncology
      • • Department of Medical Oncology
      • • Lank Center for Genitourinary Oncology
      Boston, Massachusetts, United States
    • Harvard Medical School
      • Department of Radiation Oncology
      Boston, Massachusetts, United States
    • The Bracton Centre, Oxleas NHS Trust
      Дартфорде, England, United Kingdom
  • 2013
    • Georgetown University
      • Department of Urology
      Washington, D. C., DC, United States
    • Lancaster General Hospital
      Lancaster, Pennsylvania, United States
    • Comprehensive Cancer Centers of Nevada
      Las Vegas, Nevada, United States
    • Albert Einstein College of Medicine
      • Department of Medical Oncology
      New York City, NY, United States
    • University of Utah
      Salt Lake City, Utah, United States
    • McMaster University
      Hamilton, Ontario, Canada
    • Memorial Sloan-Kettering Cancer Center
      • Genitourinary Oncology Service
      New York City, New York, United States
  • 2012–2013
    • University of Alabama at Birmingham
      • Department of Medicine
      Birmingham, AL, United States
    • Seoul National University Hospital
      Sŏul, Seoul, South Korea
    • Stanford University
      • Stanford Cancer Institute
      Stanford, CA, United States
  • 2009–2013
    • Tom Baker Cancer Centre
      Calgary, Alberta, Canada
    • Harvard University
      • Department of Nutrition
      Cambridge, Massachusetts, United States
    • Analysis Group
      Boston, Massachusetts, United States
    • Beth Israel Deaconess Medical Center
      • Division of Hematology/Oncology
      Boston, MA, United States
  • 2011–2012
    • Brigham and Women's Hospital
      • • Department of Medicine
      • • Center for Brain Mind Medicine
      Boston, MA, United States
    • Boston Medical Center
      Boston, Massachusetts, United States
    • Vancouver Prostate Centre
      Vancouver, British Columbia, Canada
    • The University of Calgary
      Calgary, Alberta, Canada
  • 2010–2011
    • University of Texas MD Anderson Cancer Center
      • • Department of Urology
      • • Division of Radiation Oncology
      Houston, TX, United States
    • Tulane University
      New Orleans, Louisiana, United States
    • Parc de Salut Mar
      Barcino, Catalonia, Spain
  • 2006–2010
    • Cleveland Clinic
      • Department of Solid Tumor Oncology
      Cleveland, OH, United States
  • 2007
    • Institut de Cancérologie Gustave Roussy
      Île-de-France, France