Christopher G Wood

University of Texas MD Anderson Cancer Center, Houston, Texas, United States

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Publications (254)1344.2 Total impact

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    ABSTRACT: Isolated local retroperitoneal recurrence (RPR) after radical nephrectomy (RN) for renal cell carcinoma (RCC) poses a therapeutic challenge. We investigated the outcomes of patients with localized RPR treated with surgical resection. This was a retrospective single-institutional study of 102 patients with RPR treated with surgery from 1990-2014. Demographics, clinical and pathological features, location of RPR, perioperative complications were reported using descriptive statistics. Recurrence free survival (RFS) and cancer-specific survival (CSS) were studied using univariate and multivariate analyses. Median age at RPR diagnosis was 55 years (IQR 49-64). Sixty-two (60.8%) patients were pT3-4 and 20 (19.6%) were pN1. No patients had distant metastatic disease at time of RPR surgery. Median time from nephrectomy to RPR diagnosis was 19 months (IQR 5-38.8). The median size of resected RPR was 4.5cm (IQR 2.7-7). Median follow up after RPR surgery was 32 months (IQR 16-57). Metastatic progression was observed in 60 (58.8%) patients after RPR surgery. Neoadjuvant and salvage systemic therapy were administered in 46 (45.1%) and 48 (47.1%) patients, respectively. On multivariate analysis, pathological nodal stage at original nephrectomy and maximum diameter of RPR were identified as independent risk factors for cancer specific death. Clinico-pathological factors at the time of nephrectomy as well as RPR surgery are important prognosticators. Aggressive surgical resection offers potential cure in a substantial number of patients with RPR with acceptable complications, and still plays a dominant role in the management of isolated locally recurrent RCC. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
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    ABSTRACT: We conducted multilevel analyses to identify potential susceptibility loci for renal cell carcinoma (RCC), which may be overlooked in traditional genome-wide association studies (GWAS). A gene set enrichment analysis was performed utilizing a GWAS dataset comprised of 894 RCC cases and 1,516 controls using GenGen, SNP ratio test, and ALIGATOR. The antigen processing and presentation pathway was consistently significant (P = 0.001, = 0.004, and < 0.001, respectively). Versatile gene-based association study approach was applied to the top-ranked pathway and identified the driven genes. By comparing the expression of the genes in RCC tumor and adjacent normal tissues, we observed significant overexpression of HLA genes in tumor tissues, which was also supported by public databases. We sought to validate genetic variants in antigen processing and presentation pathway in an independent GWAS dataset comprised of 1,311 RCC cases and 3,424 control subjects from the National Cancer Institute; one SNP, rs1063355, was significant in both populations (Pmeta-analysis = 9.15 × 10-4, Pheterogeneity = 0.427). Strong correlation indicated that rs1063355 was a cis-expression quantitative trait loci which associated with HLA-DQB1 expression (Spearman's rank r = -0.59, p = 5.61 × 10-6). The correlation was further validated using a public dataset. Our results highlighted the role of immune-related pathway and genes in the etiology of RCC.
    Oncotarget 02/2015; 6(6):4097-109. · 6.63 Impact Factor
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    ABSTRACT: Renal cell carcinoma with sarcomatoid dedifferentiation (sRCC) is an aggressive malignancy associated with a poor prognosis. Although existing literature focuses on patients presenting with metastatic disease, characteristics and outcomes for patients with localized disease are not well described. We aimed to evaluate postnephrectomy characteristics, outcomes, and predictors of survival in patients with sRCC who presented with clinically localized disease. An institutional review board-approved review from 1986 to 2011 identified 77 patients who presented with clinically localized disease, underwent nephrectomy, and had sRCC in their primary kidney tumor. Clinical and pathologic variables were captured for each patient. Overall survival (OS) and recurrence-free survival (RFS) were calculated for all patients and those who had no evidence of disease (NED) following nephrectomy, respectively. Comparisons were made with categorical groupings in proportional hazards regression models for univariable and multivariable analyses. OS for the entire cohort (n = 77) at 2 years was 50%. A total of 56 (77%) patients of the 73 who has NED following nephrectomy experienced a recurrence, with a median time to recurrence of 26.2 months. On multivariable analysis, tumor stage, pathologically positive lymph nodes, and year of nephrectomy were significant predictors of both OS and recurrence-free survival. Limitations include the retrospective nature of this study and relatively small sample size. Long-term survival for patients with sRCC, even in clinically localized disease, is poor. Aggressive surveillance of those who have NED following nephrectomy is essential, and further prospective studies evaluating the benefit of adjuvant systemic therapies in this cohort are warranted. Copyright © 2014 Elsevier Inc. All rights reserved.
    Urologic Oncology 02/2015; DOI:10.1016/j.urolonc.2014.11.021 · 3.36 Impact Factor
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    ABSTRACT: Renal cell carcinoma (RCC) is an immunogenic and proangiogenic cancer, and anti-angiogenic therapy is the current mainstay of treatment. RCC patients develop innate or adaptive resistance to anti-angiogenic therapy. There is a need to identify biomarkers which predict therapeutic resistance and guide combination therapy. Methods: Tissue microarrays with triplicate cores for each case were generated from 33 unaffected kidneys, 41 untreated primary RCC, and 42 bevacizumab and 39 sunitinib pretreated primary RCC from patients with metastatic RCC. Immunohistochemistry was used to visualize immune cell infiltration. Staining quantitation was performed using a Vectra multispectral system. Statistical analysis was performed using unpaired Student´s t-test. Results: We assessed the interaction between anti-angiogenic therapy and tumor immune microenvironment, and determined their impact on clinical outcome. Here we found that anti-angiogenic therapy treated RCC primary tumors demonstrated increased infiltration of CD4+ and CD8+ T lymphocytes, which was inversely related to patient survival. Furthermore, anti-angiogenic therapy treated specimens showed higher infiltration of CD4+FOXP3+regulatory T cells (Tregs) and enhanced expression of checkpoint ligand programed death-ligand 1 (PD-L1). Both immunosuppressive features were correlated with T lymphocyte infiltration and were negatively related to patient overall survival (OS) and/or progression free survival (PFS). Treatment of RCC cell lines and RCC xenografts in immunodeficient mice with sunitinib also increased tumor PD-L1 expression. Conclusions: This study indicates that anti-angiogenic treatment may both positively and negatively regulate the tumor immune microenvironment. These findings generate hypotheses on resistance mechanisms to antiangiogenic therapy, and will guide the development of combination therapy with PD-1/PD-L1 blocking agents.
    2015 Genitourinary Cancers Symposium of the American Society of Clinical Oncology, J Clin Oncol 33, 2015 (suppl 7; abstr 419); 02/2015
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    ABSTRACT: Variation of mitochondrial DNA copy number (mtDNAcn) in peripheral blood leukocytes (PBLs) has been associated with the risk of various cancers, including renal cell carcinoma (RCC). We assessed the association between mtDNAcn and clear cell RCC (ccRCC) risk in 608 cases and 629 controls frequency-matched on age and gender. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, BMI, smoking status, history of hypertension, total energy intake and physical activity. Our results suggest an association between low mtDNAcn and ccRCC risk (OR = 1.28, 95% CI: 0.97-1.68, P=0.09). Lower mtDNAcn was associated with increased ccRCC risk in younger individuals (Age<60, OR=1.68, 95% CI: 1.13-2.49, P=0.01), women (OR=1.66, 95% CI: 1.03-2.73, P=0.04), individuals without history of hypertension (OR=1.62, 95% CI: 1.09-2.41, P=0.02) and individuals with low physical activity levels (OR=1.55 95% CI: 1.02-2.37, P=0.05). We observed significant and marginally significant interactions between both age and history of hypertension and mtDNAcn in elevating ccRCC risk (P for interaction=0.04 and 0.07, respectively). Additionally, low mtDNAcn was associated with ccRCC risk in younger individuals with low levels of physical activity [ORs and 95% CI for medium and low physical activity levels respectively, 2.31 (1.18-4.52) and 2.09 (1.17-3.75), p-interaction 0.04]. To our knowledge, this is the first report to investigate the role of mtDNAcn in the clear cell renal cell carcinoma subtype and the first to suggest that this association may be modified by risk factors including age, gender, history of hypertension and physical activity. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
    Carcinogenesis 12/2014; DOI:10.1093/carcin/bgu248 · 5.27 Impact Factor
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    ABSTRACT: Background Renal neuroendocrine tumors (NET), comprising carcinoid tumors and small cell carcinomas, are a rare group of neoplasms. The rarity of these tumors poses a diagnostic and therapeutic challenge. Our purpose was to characterize the cases treated at a tertiary cancer center and to evaluate patients’ outcomes with the available treatment modalities. Methods This is a retrospective study of patients with renal NET seen at The University of Texas MD Anderson Cancer Center between January 1, 2001, and January 1, 2011. Patient and tumor data were analyzed by descriptive statistical methods. Results Three cases of carcinoid tumors and six cases of small cell carcinoma were identified. The median age at diagnosis was 53 years for patients with carcinoid and 65 years for patients with small cell carcinoma. The most common presenting symptoms were back pain, flank pain, and hematuria. The morphological appearance of the tumor cells and their immunohistochemical reactivity for neuroendocrine markers and cytokeratin helped establish the diagnosis. Nephrectomy was the mainstay of treatment for carcinoid tumors, yielding good long-term results, even in the presence of metastases. Surgery and chemotherapy were utilized for small cell carcinoma of the kidney. The median overall survival for patients with small cell carcinoma of the kidney was 17.3 months. Conclusion Renal carcinoid tumors are indolent and are associated with prolonged survival, while small cell carcinomas of the kidney are aggressive tumors with relatively short overall survival. Although palliative in nature, cytotoxic chemotherapy is the mainstay of therapy and is best given before surgery.
    Clinical Genitourinary Cancer 12/2014; DOI:10.1016/j.clgc.2014.06.008 · 1.69 Impact Factor
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    ABSTRACT: To validate the independent predictive value of Ki-67 in patients with high-grade upper tract urothelial carcinoma (UTUC). 475 patients from the international UTUC collaboration who underwent extirpative surgery for high-grade UTUC were included in this study. Immunohistochemical staining for Ki-67 was performed on tissue microarray (TMA) formed from this patient cohort. Ki-67 expression was assessed in a semi-quantitative fashion and considered overexpressed at a cut-off of 20%. Multivariate analyses (MVA) were performed to assess independent predictors of oncological outcomes and Harrell's C indices (HCI) were calculated for predictive models. Median age of the cohort was 69.7 years and 55.2% of patients were male. Ki-67 was overexpressed in 25.9% of patients. Ki-67 overexpression was significantly associated with ureteral tumor location, higher pT-stage, lymphovascular invasion, sessile tumor architecture, tumor necrosis, concomitant carcinoma in situ (CIS), and regional lymph node metastases. In Kaplan-Meier analyses, overexpressed Ki-67 was associated with worse recurrence-free (RFS) (HR 12.6, p<0.001) and cancer-specific survival (CSS) (HR 15.8, p<0.001). In MVA, Ki-67 was an independent predictor of RFS (HR 1.6, 95% CI 1.07-2.30, p=0.021) and CSS (HR 1.9, 95% CI 1.29-2.90, p=0.001). Ki-67 improved HCI from 0.66 to 0.70 (p<0.0001) for both RFS and CSS in our preoperative model, and from 0.81 to 0.82 (p=0.0018) for RFS and 0.81 to 0.83 (p=0.005) for CSS in our post-operative model. Ki-67 was validated as an independent prognostic predictor of RFS and CSS in patients treated with extirpative surgery for high-grade UTUC in a large, multi-institutional cohort. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.
    The Journal of Urology 11/2014; 193(5). DOI:10.1016/j.juro.2014.11.007 · 3.75 Impact Factor
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    ABSTRACT: To evaluate the prognostic value of altered mammalian target of rapamycin (mTOR) pathway biomarkers in upper tract urothelial carcinoma (UTUC). We performed a multi-institutional review of clinical and pathologic information on patients receiving extirpative surgery for UTUC from 1990 to 2008. Immunohistochemistry for phosphorylated-S6, mTOR, phosphorylated-mTOR, PI3K, phosphorylated-4EBP1, phosphorylated-AKT, PTEN, HIF-1a, raptor, and cyclin D was performed on tissue microarrays from radical nephroureterectomy (RNU) specimens. Prognostic markers were identified and the significance of altered markers was assessed with the Kaplan-Meier analysis and the Cox regression analysis. Six hundred twenty patients were included. Over a median follow-up of 27.3 months, 24.6% of patients recurred and 21.8% died of UTUC. On multivariate analysis, PI3K (odds ratio, 1.28; P = .001) and cyclin D (odds ratio, 3.45; P = .05) were significant predictors of clinical outcomes. Cumulative marker score was defined as low risk (no altered markers or 1 altered marker) or high risk (cyclin D and PI3K altered). Patients with high-risk marker score had a significantly higher proportion of high-grade disease (91% vs 71%; P <.001), non-organ-confined disease (61% vs 33%; P <.001), and lymphovascular invasion (35% vs 20%; P = .001). The Kaplan-Meier analysis demonstrated a significant difference in cancer-specific mortality (CSM) based on the risk groups. On Cox regression multivariate analysis for CSM incorporating non-organ-confined disease, grade, lymphovascular invasion, tumor architecture, and marker score, high-risk biomarker score was an independent predictor of CSM (hazard ratio, 1.5; 95% confidence interval, 1.04-2.3; P = .03). Alterations in mTOR pathway correlate with established adverse pathologic features and independently predict inferior oncologic outcomes. Incorporation of mTOR-based marker profiles may allow for enhanced patient counseling, risk stratification, and individualized treatment regimens. Copyright © 2014 Elsevier Inc. All rights reserved.
    Urology 11/2014; 84(5):1134-40. DOI:10.1016/j.urology.2014.07.050 · 2.13 Impact Factor
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    ABSTRACT: Objective To characterize the clinical, radiologic and histologic features of Mucinous Tubular and Spindle Cell Carcinoma (MTSCC), as well as oncologic outcomes.Patients and methodsThis is a single institution retrospective analysis of all MTSCC patients from 2002-2011.Patients were excluded if MTSCC could not be confirmed on pathology re-review (n=4).Clinical characteristics, pathology, imaging, and outcomes were reviewed for the 19 included patients.ResultsMedian age at diagnosis was 59 years (range 17-71) with a female predominance (78.9%).On contrast enhanced CT scan, MTSCC enhanced less than the cortex during the corticomedullary phase. Mean tumor attenuation was 36 HU (range 24-48), 67 HU (range 41-133), 89 HU (range 49-152), and 76 HU (range 52-106) in the precontrast, corticomedullary, nephrographic and excretory phases, respectively.Sixteen patients were treated with partial (N=5) or radical nephrectomy (N=11) for pT1(62.5%), pT2(31.3%), and pT3a disease(6.3%). One patient had active surveillance. Of 3 patients(13.0%) managed with energy ablation, there was one recurrence that was treated with salvage surgery.One patient(5.3%) had metastatic disease at diagnosis and died of disease 64.7 months later. A patient with a pT2bN0M0 MTSCC with sarcomatoid dedifferentiation developed bone metastases 9.5 months after diagnosis and was alive at 19.0 months. The remainder were free of recurrence or progression.ConclusionMTSCC is a rare RCC variant. In this largest series to date, MTSCC presented at a broad range of ages and displayed a female predilection.Imaging and pathologic features of MTSCC display some overlap with papillary RCC.MTSCC is associated with excellent outcomes overall, but is not universally indolent.
    BJU International 11/2014; DOI:10.1111/bju.12992 · 3.13 Impact Factor
  • Mehrad Adibi, Jose A Karam, Christopher G Wood
    European Urology 10/2014; DOI:10.1016/j.eururo.2014.10.030 · 12.48 Impact Factor
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    ABSTRACT: Patients with locally advanced renal cell carcinoma (RCC) represent a subset of patients who may benefit from retroperitoneal lymph node dissection (RPLND). We aimed to identify preoperative clinical predictors of positive lymph nodes in patients with RCC without distant metastasis who underwent RPLND.
    The Journal of Urology 10/2014; DOI:10.1016/j.juro.2014.10.096 · 3.75 Impact Factor
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    ABSTRACT: OBJECTIVE. The purpose of this study is to evaluate whether intraoperative ultrasound (IOUS) during open partial nephrectomy alters the surgical management for renal cell cancer (RCC). MATERIALS AND METHODS. One hundred ninety-eight consecutive patients undergoing IOUS during open partial nephrectomy for RCC were selected for retrospective review of clinical and imaging data. Patient age and sex, the local extent of the primary lesion, and the presence of additional lesions were recorded. Ultrasound findings were compared with preoperative CT or MRI to determine whether the IOUS findings changed surgical management. Summary statistics were performed to assess what percentage of patients with additional IOUS findings had a change in their surgical management. The Kaplan-Meier method was used to estimate 5-year overall survival (OS) and event-free survival (EFS) rates for all patients. Patients were followed for 9-12 years to assess survival and measure recurrence rates. RESULTS. Twenty-one of 198 patients (10.6%; 95% CI, 6.7-15.8%) had additional findings on IOUS not seen on preoperative imaging. As a result, surgery was modified in 15 of these 21 patients (71.4%; 95% CI, 47.8-88.7%). The 5-year OS rate was 81%, and the EFS rate was 76% for the whole group; most deaths were due to unrelated causes. There was no statistically significant difference in OS (p = 0.867) and EFS (p = 0.069) rates among patients who had a change of management because of additional lesions seen by IOUS. CONCLUSION. IOUS performed during open partial nephrectomy for resection of RCC shows additional findings compared with preoperative cross-sectional imaging that may alter surgical management.
    American Journal of Roentgenology 10/2014; 203(4):822-827. DOI:10.2214/AJR.13.12254 · 2.74 Impact Factor
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    ABSTRACT: Background: Ewing sarcoma family of tumors (ESFT) of the kidney are exceedingly rare. Given the rarity of this neoplasm and the complexity associated with its management, information regarding treatment and outcome is warranted. Materials and Methods: We conducted a retrospective study of patients with ESFT of the kidney who were treated at MDACC between January 1, 2001 and January 1, 2011. Descriptive statistics were used. Results: Thirteen patients were identified (median age, 33 y; male:female 11:2). Common presenting symptoms were back pain, flank pain, and hematuria. Six patients had metastatic disease at presentation. Initial diagnostic biopsy was performed in 6 patients. Immunohistochemistry showed strong positivity for CD99 (mic2) and cytogenetic analysis demonstrated evidence of EWSR1 fusion gene in 8 cases. Nine patients underwent nephrectomy. Frequently used chemotherapy regimens consisted of vincristine, doxorubicin, and ifosfamide. Median overall survival was 17.2 months. Three patients were alive at the time of analysis, at 2, 7, and 11 years from diagnosis (the latter without evidence of disease). Conclusions: Renal ESFT carry a guarded prognosis with limited response to therapy and short median overall survival. For patients with metastatic disease, diagnostic biopsy and sarcoma-based chemotherapy regimens are recommended as upfront therapeutic strategy. The role of nephrectomy in the metastatic setting is unclear. Future studies with novel therapies are needed.
    American Journal of Clinical Oncology 09/2014; DOI:10.1097/COC.0000000000000128 · 2.61 Impact Factor
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    ABSTRACT: Dietary factors may affect risk of renal cell carcinoma (RCC). In an ongoing case-control study of RCC initiated in Houston, Texas, in 2002, we identified 3 empirically derived dietary patterns: "fruits and vegetables," "American/Western," and "Tex-Mex." Among 659 RCC cases and 699 controls, we evaluated associations of these dietary patterns with RCC risk and whether the associations varied by obesity status, smoking status, physical activity level, history of hypertension, and genetic variants previously identified via genome-wide association studies. Among persons in the highest categories of adherence versus the lowest, the "fruits and vegetables" dietary pattern was associated with an approximately 50% lower RCC risk (Ptrend < 0.001), while "American/Western" dietary pattern scores were positively associated with a 2-fold higher risk (Ptrend < 0.001). We observed synergistic interaction between the American/Western pattern and hypertension status: The odds ratio (highest tertile vs. lowest) among persons with hypertension was 2.23 (95% confidence interval: 1.43, 3.45), as compared with 1.76 (95% confidence interval: 1.16, 2.70) among persons without hypertension (additive Pinteraction = 0.01). A variant (rs718314) in the inositol 1,4,5-trisphosphate receptor, type 2 gene (ITPR2) was found to interact with the American/Western dietary pattern in relation to RCC risk (additive Pinteraction = 0.03). ITPR2 has been shown to affect nutrient metabolism and central obesity. Dietary patterns, genetic variants, and host characteristics may individually and jointly influence susceptibility to RCC.
    American Journal of Epidemiology 07/2014; 180(5). DOI:10.1093/aje/kwu158 · 4.98 Impact Factor
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    ABSTRACT: Purpose: Cytoreductive nephrectomy (CN) remains the standard of care for appropriately selected patients with metastatic renal cell carcinoma (mRCC). Although the role of partial nephrectomy (PN) is well accepted in patients with localized disease, limited data are available regarding PN in the metastatic setting. We sought to identify the indications and outcomes for PN in the setting of mRCC with particular attention to different PN subgroups. Materials and Methods: We analyzed data from a consecutive cohort of 33 patients with mRCC who underwent PN at a single institution between 1996 and 2011. Non-parametric statistics were used to compare PN subgroups. Overall survival (OS) was estimated using Kaplan-Meier method, and survival functions were compared using the log-rank test. Results: Eight patients presented with bilateral synchronous renal masses; 20 with a metachronous contralateral renal mass; and 5 with a unilateral renal mass. Overall, 22 patients (67%) died of disease at a median of 27 months after PN. Patients who underwent PN for a metachronous contralateral renal mass and for a renal mass ≤4cm had the best OS (61 months and 42 months, respectively). Median OS for patients with and without metastatic disease at original diagnosis was 27 and 63 months, respectively (p=0.003). Conclusions: Our findings suggest that the presence of metastasis at original diagnosis and the timing of presentation of the PN index lesion play an important role in survival. These factors should be taken into consideration when determining which patients would benefit from partial nephrectomy in the setting of mRCC.
    The Journal of urology 07/2014; 192(1). DOI:10.1016/j.juro.2014.01.086 · 3.75 Impact Factor
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    ABSTRACT: BACKGROUND High-grade upper tract urothelial carcinoma (UTUC) is frequently upstaged after surgery and is associated with uniformly poor survival. Neoadjuvant chemotherapy may offer a way to improve clinical outcomes. The authors compared the survival rates of patients with UTUC who received neoadjuvant chemotherapy before surgery with the rates among patients who did not.METHODSA retrospective review was conducted of patients with high-risk UTUC who received neoadjuvant chemotherapy followed by surgery from 2004 to 2008 (study group) compared with a matched cohort who underwent initial surgery from 1993 to 2003 (control group). Fisher exact tests, Wilcoxon rank-sum tests, and Kaplan-Meier methods were used. The log-rank test and Cox proportional-hazards models were used to evaluate the association of the 2 outcomes with patient, treatment, and tumor characteristics in univariate and multivariate models.RESULTSOf 112 patients, there were 31 in the study group and 81 in the control group. Patients who received neoadjuvant chemotherapy had improved overall survival (OS) and disease-specific survival (DSS) with a 5-year DSS rate of 90.1% and a 5-year OS rate of 80.2% versus DSS and OS rates of 57.6% for those who underwent initial surgery (P = .0204 and P = .0015, respectively). In multivariate analyses, the neoadjuvant group had a lower risk of mortality (OS: hazard ratio, 0.42 [P = .035]; DSS: hazard ratio, 0.19 [P = .006]).CONCLUSIONS Neoadjuvant chemotherapy improved the survival of patients with UTUC compared with a matched historic cohort of patients who underwent initial surgery. Patients with high-risk UTUC should be considered for neoadjuvant chemotherapy in view of the limited opportunity to administer effective cisplatin-based chemotherapy after nephroureterectomy. Cancer 2014. © 2014 American Cancer Society.
    Cancer 06/2014; 120(12). DOI:10.1002/cncr.28655 · 4.90 Impact Factor
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    ABSTRACT: Purpose: MITF/TFE translocation renal cell carcinoma (TRCC) is a rare subtype of kidney cancer. Its incidence and the genome-wide characterization of its genetic origin have not been fully elucidated. Experimental design: We performed RNA and exome sequencing on an exploratory set of TRCC (n=7), and validated our findings using The Cancer Genome Atlas (TCGA) clear-cell RCC (ccRCC) dataset (n=460). Results: Using the TCGA dataset, we identified 7 TRCC (1.5%) cases and determined their genomic profile. We discovered three novel partners of MITF/TFE (LUC7L3, KHSRP and KHDRBS2), which are involved in RNA splicing. TRCC displayed a unique gene expression signature as compared to other RCC types, and showed activation of MITF, the transforming growth factor β1 and the PI3K complex targets. Genes differentially spliced between TRCC and other RCC types were enriched for MITF and ID2 targets. Exome sequencing of TRCC revealed a distinct mutational spectrum as compared to ccRCC, with frequent mutations in chromatin remodeling genes (six of eight cases, three of which from the TCGA). In two cases, we identified mutations in INO80D, an ATP-dependent chromatin remodeling gene, previously shown to control the amplitude of the S phase. Knockdown of INO80D decreased cell proliferation in a novel cell line bearing LUC7L3-TFE3 translocation. Conclusions: This genome-wide study defines the incidence of TRCC within a ccRCC-directed project and expands the genomic spectrum of TRCC by identifying novel MITF/TFE partners involved in RNA splicing and frequent mutations in chromatin remodeling genes.
    Clinical Cancer Research 06/2014; 20(15). DOI:10.1158/1078-0432.CCR-13-3036 · 8.19 Impact Factor
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    Riaz J. Karmali, Hiroo Suami, Christopher G. Wood, Jose A. Karam
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    ABSTRACT: Lymphatic drainage in renal cell carcinoma (RCC) is unpredictable, however, basic patterns can be observed in cadaveric and sentinel lymph node mapping studies in patients with RCC. The existence of peripheral lymphovenous communications at the level of the renal vein has been shown in mammals but remains unknown in humans. The sentinel lymph node biopsy technique can be safely applied to map lymphatic drainage patterns in patients with RCC. Further standardisation of sentinel node biopsy techniques is required to improve the clinical significance of mapping studies. Understanding lymphatic drainage in RCC may lead to an evidence-based consensus on the surgical management of retroperitoneal lymph nodes.
    BJU International 05/2014; 114(6). DOI:10.1111/bju.12814 · 3.13 Impact Factor
  • Dae Y Kim, Jose A Karam, Christopher G Wood
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    ABSTRACT: Numerous biological pathways are affected in renal cell carcinoma and the introduction of targeted agents has improved the survival of patients with advanced and metastatic disease. Durable and long-lasting cure is rarely achieved, and in select cases, the excision of metastatic deposits has shown to increase survival. Clinical trials of targeted agents are being explored as neoadjuvant and adjuvant therapies with the role of metastasectomy evolving in the treatment paradigm. This review examines published reports of metastasectomy and its developing role in the era of targeted therapy. A Medline search was conducted using keywords "metastasectomy," "renal cell carcinoma," and "targeted therapy," and selected articles are discussed by examining prognostic stratification and metastasectomy in major anatomic regions. Most published reports span earlier periods of immunotherapy and chemotherapy, and henceforth, discussions are in historical context in this review. Although there is lack of Level 1 evidence, reports have suggested the prognostic value and survival benefit for metastasectomy in lesions that are amenable to complete resection after longer disease-free intervals in carefully selected patients with adequate performance status. Therefore, the role of metastasectomy must be further elucidated in the era of targeted therapy.
    World Journal of Urology 04/2014; DOI:10.1007/s00345-014-1293-6 · 3.42 Impact Factor
  • Stephen H Culp, Jose A Karam, Christopher G Wood
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    ABSTRACT: Despite level 1 evidence demonstrating a survival benefit of cytoreductive nephrectomy (CN) in well-selected patients with metastatic renal cell carcinoma (mRCC) in the cytokine era, its role in the contemporary period of targeted therapy remains understudied. To help facilitate improved patient selection for CN and clinical trial design in the targeted therapy era, this study sought to identify factors associated with RCC-specific survival in patients diagnosed with mRCC and undergoing CN between 2005 and 2010 using a large population-based cohort. Patients diagnosed with mRCC and undergoing CN between 2005 and 2010 were identified from the Surveillance Epidemiology and End Results cancer database. Kaplan-Meier methods were used to calculate disease-specific survival. Stepwise multivariable Cox proportional hazards regression analysis was used to identify factors independently associated with risk of RCC-specific death. A total of 2,478 patients were identified who were eligible for analysis with a median disease-specific survival of 21 months (95% CI: 19, 22). Factors independently associated with an increased risk of RCC-specific death included age at diagnosis≥60 years, African American race, higher American Joint Committee on Cancer T stage (≥T3), high Fuhrman nuclear grade (3 or 4), primary tumor size≥7cm, regional lymphadenopathy, both distant lymph node and visceral metastases, and sarcomatoid histology. A higher number of adverse factors correlated with an increased risk of RCC-specific death (P<0.001). Factors associated with RCC-specific survival identified in this large population-based study can be used to better stratify patients suitable for CN and to help with future clinical trial design and interpretation.
    Urologic Oncology 04/2014; 32(5). DOI:10.1016/j.urolonc.2013.12.003 · 3.36 Impact Factor

Publication Stats

5k Citations
1,344.20 Total Impact Points

Institutions

  • 2002–2015
    • University of Texas MD Anderson Cancer Center
      • • Department of Urology
      • • Genitourinary Medical Oncology
      • • Department of Epidemiology
      Houston, Texas, United States
  • 2006–2014
    • University of Houston
      Houston, Texas, United States
  • 2010–2013
    • University of Texas Southwestern Medical Center
      • Department of Urology
      Dallas, Texas, United States
    • Peter MacCallum Cancer Centre
      • Peter MacCallum Cancer Center
      Melbourne, Victoria, Australia
  • 2008–2009
    • Keio University
      Edo, Tōkyō, Japan
  • 2003
    • Memorial Sloan-Kettering Cancer Center
      New York, New York, United States
    • University of California, Davis
      • Department of Urology
      Davis, CA, United States