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ABSTRACT: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Radiological imaging is heavily relied on for follow up after renal ablative therapy. We show that while this is largely reliable, there are quantifiable false negative and false positive findings. A non-involuting zone of ablation should be considered for multisite-directed core biopsies even in the absence of detectable enhancement. OBJECTIVE: To evaluate our experience with radiofrequency ablation (RFA) for renal masses and to report on clinical, radiological and post-RFA biopsy results. PATIENTS AND METHODS: The study collected clinical, radiological and pathological data from 150 consecutive patients who were treated with RFA of a renal mass between 2002 and 2008 at a tertiary referral centre. Post-ablation biopsies were performed in patients with non-involuting lesions or suspicion of recurrence on imaging. Comparisons were performed using the Mann-Whitney U-test. Survival was estimated using the Kaplan-Meier method. RESULTS: Renal malignancy was found in 72.1% of patients based on the initial diagnostic biopsy. Median tumour size was 2.6 cm, 22.7% of patients had a solitary kidney, and most were central tumours. The mean follow-up period was 40.1 month. There was no recurrence in 96.7% of the entire cohort. Cancer-specific survival for 106 patients with sporadic, localized, biopsy proven renal malignancy was 100% at 38.5 months. Biopsies were obtained in 43 patients for a median of 21 months after RFA. Among 38 patients who had biopsy for non-involuting, non-enhancing zones of ablation, three (7.9%) were positive. CONCLUSIONS: Short-term cancer-specific survival after RFA remains excellent and most cases are successful based on a combination of imaging and post-ablation biopsies performed almost 2 years after treatment. There were four out of 150 (2.7%) patients who had recurrences with tissue confirmation; one of these patients was detected on imaging and three (2%) were radiologically occult. The absence of enhancement in the setting of non-involuting lesions is not always a guarantee of a successful ablation.
BJU International 03/2013; · 2.84 Impact Factor
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ABSTRACT: BACKGROUND: Few studies have examined factors associated with the quality of life (QOL) of patients with renal tumors. Illness uncertainty may influence QOL. OBJECTIVE: To prospectively examine the influence of uncertainty on general and cancer-specific QOL and distress in patients undergoing watchful waiting (WW) for a renal mass. DESIGN, SETTING, AND PARTICIPANTS: In 2006-2010, 264 patients were enrolled in a prospective WW registry. The decision for WW was based on patient, tumor, and renal function characteristics at the discretion of the urologist and medical oncologist in the context of the physician-patient interaction. Participants had suspected clinical stage T1-T2 disease, were aged ≥18 yr, and spoke and read English. The first 100 patients enrolled in the registry participated in this study. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Patients completed questionnaires on demographics, illness uncertainty (Mishel Uncertainty in Illness Scale), general QOL (Medical Outcomes Study 36-item short-form survey), cancer-specific QOL (Cancer Rehabilitation Evaluation System-Short Form), and distress (Impact of Events Scale) at enrollment and at 6, 12, and 24 mo. Age, gender, ethnicity, tumor size, estimated glomerular filtration rate, comorbidities, and assessment time point were controlled for in the models. RESULTS AND LIMITATIONS: Among the sample, 27 patients had biopsies, and 17 patients had proven renal cell carcinoma. Growth rate was an average of 0.17cm/yr (standard deviation: 0.35). Mean age was 72.5 yr, 55% of the patients were male, and 84% of the patients were Caucasian. Greater illness uncertainty was associated with poorer general QOL scores in the physical domain (p=0.008); worse cancer-related QOL in physical (p=0.001), psychosocial (p<0.001), and medical (p=0.034) domains; and higher distress (p<0.001). CONCLUSIONS: This study is among the first to prospectively examine the QOL of patients with renal tumors undergoing WW and the psychosocial factors that influence QOL. Illness uncertainty predicted general QOL, cancer-specific QOL, and distress. These factors could be targeted in psychosocial interventions to improve the QOL of patients on WW.
European urology 02/2013; · 7.67 Impact Factor
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ABSTRACT: Renal cell carcinoma (RCC) is an important contributor to cancer-specific mortality worldwide. Targeted agents that inhibit key subtype-specific signaling pathways have improved survival times and have recently become part of the standard of care for this disease. Accurately diagnosing and classifying RCC on the basis of tumor histology is thus critical. RCC has traditionally been divided into clear-cell and non-clear-cell categories, with papillary RCC forming the most common subtype of non-clear-cell RCC. Renal neoplasms with overlapping histologies, such as tumors with mixed clear-cell and papillary features and hybrid renal oncocytic tumors, are increasingly seen in contemporary practice and present a diagnostic challenge with important therapeutic implications. In this review, we discuss the histologic, immunohistochemical, cytogenetic, and clinicopathologic aspects of these differential diagnoses and illustrate how the classification of RCC has evolved to integrate both the tumor's microscopic appearance and its molecular fingerprint.
Chinese journal of cancer 12/2012;
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ABSTRACT: OBJECTIVES:: This study evaluated the effect of tyrosine kinase inhibitors (TKIs) on the brain metastasis (BM), local control (LC), and overall survival (OS) of patients with renal cell carcinoma (RCC) with BM. METHODS:: A retrospective review of patients with RCC BM was conducted. Eligible patients from 2 eras: pre-TKI, 2002 to 2003 and post-TKI, 2006 to 2007, were identified. Prognostic factors, use, and type of systemic therapy were noted. The timing, number, size, and treatment modality data for each BM were recorded. Use of TKI and BM treatment modality were correlated to LC and OS. RESULTS:: Eighty-one patients with 216 BMs were identified. Thirty-seven patients had BM at diagnosis and the remaining 44 were found to have BM at a later point. Forty-one patients never received a TKI and the remaining 40 received TKIs. Stereotactic radiosurgery, surgery, whole brain radiotherapy, or no local brain treatment was used for 89, 19, 24, and 75 lesions, respectively. The median OS from BM diagnosis was 5.4 months for the whole group: 4.4 versus 6.71 months in the never-TKI versus TKI groups, respectively. Patients who received TKIs post-BM development had a median OS of 23.6 months versus 2.08 and 4.41 months for the patients who received TKIs pre-BM or never-TKI, respectively (P=0.0001). LC was statistically superior in lesions managed with surgery or stereotactic radiosurgery versus the no local therapy. CONCLUSIONS:: In patients with RCC and BM, TKIs are associated with a trend of improved OS, but no significant improvement in LC of BM. They may provide a significant benefit to patients with BM with no prior TKI exposure.
American journal of clinical oncology 08/2012; · 2.21 Impact Factor
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ABSTRACT: OBJECTIVE:: To determine the clinical activity and safety of the combination of pemetrexed and gemcitabine in advanced nonclear cell renal cell carcinoma (nccRCC). METHODS:: In this phase II study, patients received pemetrexed 500 mg/m intravenous infusion over 10 minutes on day 1 followed immediately by gemcitabine 1500 mg/m intravenously over 30 minutes on day 1, with cycles repeated every 14 days. Planned enrollment was 40 patients. The primary endpoints were objective response rate and progression-free survival (PFS). The secondary endpoints were safety and overall survival. RESULTS:: Between December 2005 and December 2008, 16 patients with locally advanced or metastatic nccRCC were enrolled. The trial was stopped early due to low efficacy and excessive toxicity. The objective response rate was 0% [95% confidence interval (CI), 0%-18%]. The median number of cycles administered was 4 (range, 1 to 12). Median PFS was 3.2 months (95% CI, 1.9-6+), and the 16-week PFS rate was 46.7% (95% CI, 19.8%-100%). Median overall survival was 23.2 months (95% CI, 12.9-38.1). The most common grade 3 or 4 adverse events were neutropenia (53%), leukopenia (53%), anemia (13%), fatigue (40%), and renal insufficiency (13%). CONCLUSIONS:: In this phase II trial in nccRCC, the combination of pemetrexed and gemcitabine was toxic and ineffective. Further development of this regimen in nccRCC is not warranted.
American journal of clinical oncology 06/2012; · 2.21 Impact Factor
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Journal of the National Comprehensive Cancer Network: JNCCN 06/2012; 10(6):690-3. · 4.41 Impact Factor
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Robert J Motzer,
Neeraj Agarwal,
Clair Beard,
Sam Bhayani,
Graeme B Bolger,
Mark K Buyyounouski,
Michael A Carducci,
Sam S Chang,
Toni K Choueiri,
Shilpa Gupta, [......],
M Dror Michaelson,
Thomas Olencki,
Roberto Pili,
Thomas W Ratliff,
Bruce G Redman,
Cary N Robertson,
Charles J Ryan,
Joel Sheinfeld,
Jue Wang,
Richard B Wilder
Journal of the National Comprehensive Cancer Network: JNCCN 04/2012; 10(4):502-35. · 4.41 Impact Factor
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ABSTRACT: Axitinib, an oral small-molecule tyrosine kinase inhibitor targeted to angiogenesis, has demonstrated activity in advanced renal cell carcinoma. Common side effects include hypertension, fatigue and dysphonia. Axitinib is currently awaiting approval as a second-line agent in the treatment of advanced renal cell carcinoma. Trials, which include treatment-naive patients, are ongoing and will study the benefit of axitinib in the first-line setting.
Future Oncology 11/2011; 7(11):1247-53. · 3.16 Impact Factor
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ABSTRACT: The biological rationale for this study came from the observation that bisphosphonates and statins affect bone metastasis in different ways and thus combination therapy may provide synergistic benefit. This pilot trial evaluated the efficacy and safety of combining a bisphosphonate and a statin in patients with RCC metastatic to bone.
Patients with RCC and bone metastasis received zoledronate and fluvastatin or atorvastatin. Patients were monitored clinically and by imaging for skeletal events. Concentrations of the bone resorption markers deoxypyridinoline (DPD) and N-telopeptide (NTX) and the bone formation marker bone-specific alkaline phosphatase (BSAP) were monitored for changes during treatment.
Eleven patients were enrolled and followed for a median of 6 months. The median time to first skeletal-related event for all patients was 9.0 months. Seven (63%) patients experienced skeletal events with a median time to first skeletal-related event of 4.0 months (range, 3-18 months); 4 patients (36%) experiences no skeletal events for a median of 12 months of follow-up (range, 2-28 months); 4 patients (36%) demonstrated treatment responses with development of sclerosis in lytic bone lesions. Differences in the median changes in biomarker levels between patients who had skeletal events and those who did not were statistically significant for DPD and NTX (P = .03 and .01, respectively) but not for BSAP (P = .4). The regimen was well tolerated, with few adverse reactions related to the study drugs.
Although the use of bone-targeting therapy combining zoledronate and fluvastatin or atorvastatin affected certain bone biomarkers and provided bone response in several patients with RCC and bone metastasis, we could not demonstrate a statistically significant improvement in time to skeletal events.
Clinical Genitourinary Cancer 09/2011; 9(2):81-8. · 2.61 Impact Factor
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Robert J Motzer,
Neeraj Agarwal,
Clair Beard,
Sam Bhayani,
Graeme B Bolger,
Michael A Carducci,
Sam S Chang,
Toni K Choueiri,
Steven L Hancock,
Gary R Hudes, [......],
Thomas Olencki,
Roberto Pili,
Thomas W Ratliff,
Bruce G Redman,
Cary N Robertson,
Charles J Ryan,
Joel Sheinfeld,
Philippe E Spiess,
Jue Wang,
Richard B Wilder
Journal of the National Comprehensive Cancer Network: JNCCN 09/2011; 9(9):960-77. · 4.41 Impact Factor
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ABSTRACT: Insights into renal cell carcinoma (RCC) biology have greatly expanded the treatment armamentarium for metastatic RCC (mRCC). Since 2005, six targeted agents have been approved by the US Food and Drug Administration (FDA) for the management of mRCC, and many new targeted therapies are in development. A number of novel VEGF Inhibitors/Multi-Tyrosine Kinase Inhibitors are currently in various stages of development. New targeted agents with novel mechanisms of action are also being studied, including Histone Deacetylase Inhibitors, Angiopoietin/TIE-2 inhibitors, Carbonic anhydrase IX inhibitors, vaccines, and others. In addition to combining currently available immunologic therapies with emerging agents, researchers are also developing novel immunologic therapies to treat mRCC, including those that block Cytotoxic T-Lymphocyte Antigen 4 (CTLA4). Several trials evaluating combinations and sequential therapy of targeted agents have been published, and several others are underway. Trials of special mRCC populations, including poor-risk disease, non-clear cell RCC (NCC-RCC), and papillary type RCC are further refining the use of targeted treatments. As new targeted agents emerge and therapies with novel mechanisms of action are developed, the treatments options available for metastatic RCC are expected to increase. New therapies will likely have fewer detrimental side effects and better efficacy, leading to better quality of life for patients.
Current clinical pharmacology. 08/2011; 6(3):189-98.
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ABSTRACT: Nephrectomy continues to be the cornerstone of treatment for localized renal cell carcinoma (RCC). Despite undergoing nephrectomy, recurrence of disease remains a concern in many patients, and different medical therapies are being investigated as means to decrease this risk. The use of the traditional immunotherapy options has not provided benefit as adjuvant treatment in this disease state. Recently, the treatment of metastatic RCC has experienced key advances with the introduction of targeted agents against the vascular endothelial growth factor (VEGF) molecule and related pathways as well as inhibitors of the mammalian target of rapamycin (mTOR), in addition to improvements in surgical technique. Additionally, there are questions about the optimal timing of systemic therapy in the context of high risk non-metastatic disease. There is optimism that locally advanced RCC might benefit from adjuvant or neoadjuvant treatment with these therapies. Ongoing clinical trials are addressing the role of targeted agents in this disease state.
Current clinical pharmacology. 08/2011; 6(3):144-50.
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ABSTRACT: Loss of chromosome 14 has been associated with poor outcomes in clear-cell renal cell carcinoma. Expression of HIFα isoforms has been linked to distinct molecular phenotypes of clear-cell renal cell carcinoma. We hypothesized that chromosome 14 loss could lead to a decrease in HIF1α levels, as its gene (HIF1A) resides in this chromosome. We analyzed 112 archival clear-cell renal cell carcinoma tumor specimens with 250K SNP microarrays. We also evaluated expression of HIFα isoforms by qPCR and immunohistochemistry in a subset of 30 patients. Loss of chromosome 14q was associated with high stage (III-IV, P=0.001), high risk for recurrence (P=0.002, RR 2.78 (1.506-5.153)) and with decreased overall survival (P=0.030) in non-metastatic clear-cell renal cell carcinoma. HIF1α mRNA and protein expression was reduced in specimens with loss of 14q (P=0.014) whereas HIF2α was not. Gain of 8q was associated with decreased overall survival (P<0.0001). Our studies confirm an association between 14q loss and clinical outcome in non-metastatic clear-cell renal cell carcinoma patients and that 8q gain is a candidate prognostic marker for decreased overall survival and appears to further decrease survival in patients with 14q loss. We have also identified that differential expression of HIF1α is associated with 14q loss. Further exploration of 8q gain, 14q loss, MYC, HIF1A and EPAS1 (HIF2α) as molecular markers of tumor behavior and prognosis could aid in personalizing medicine for patients with clear-cell renal cell carcinoma.
Modern Pathology 07/2011; 24(11):1470-9. · 4.79 Impact Factor
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ABSTRACT: Renal cell carcinoma (RCC) is the most common malignant neoplasm of the kidney, and sarcomatoid RCC is an aggressive and lethal variant. Sarcomatoid features can be seen in all types of RCC and do not constitute a separate histologic type. No cellular or genetic biomarker for the sarcomatoid variant has yet been discovered. Most systemic therapies developed for metastatic RCC are less effective in sarcomatoid RCC, although some of the cytotoxic drugs may actually be more effective for sarcomatoid RCC because of its rapid rate of proliferation. Several ongoing prospective clinical trials are investigating new drug combinations for this disease.
Expert Review of Anti-infective Therapy 06/2011; 11(6):913-20. · 2.65 Impact Factor
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ABSTRACT: Kidney and upper urinary tract cancers account for approximately 54,000 cases every year in the United States, and represent about 3.7% of adult malignancies, with more than 13,000 annual deaths. Classification of renal tumors is typically based on histomorphologic characteristics but, on occasion, morphologic characteristics are not sufficient. Each of the most common histologic subtypes harbors specific recurrent genetic abnormalities, such as deletion of 3p in conventional clear cell carcinoma, trisomy 7 and 17 in papillary renal cell carcinoma, multiple monosomies in chromophobe renal cell carcinoma, and a nearly diploid genome in benign oncocytomas. Knowledge of this information can provide diagnostic support and prognostic refinement in renal epithelial tumors. Identification of the specific subtype of a renal tumor is critical in guiding surveillance for recurrence and the appropriate use of targeted therapies. Cytogenomic arrays are increasingly being used as a clinical tool for genome-wide assessment of copy number and loss of heterozygosity in renal tumors. In addition, the improved understanding of the hereditary causes of renal tumors and their role in sporadic malignancies has led to the development of more effective targeted therapies. This review summarizes the genetic and genomic changes in the most common types of renal epithelial tumors and highlights the clinical implications of these aberrations.
Cancer Genetics 06/2011; 204(6):285-97.
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ABSTRACT: In patients with metastatic renal cell carcinoma (mRCC), the timing of systemic targeted therapy in relation to cytoreductive nephrectomy (CN) is under investigation.
To evaluate postoperative complications after the use of presurgical targeted therapy prior to CN.
A retrospective review of all patients who underwent a CN at The University of Texas M.D. Anderson Cancer Center from 2004 to 2010 was performed. Inclusion in this study required documented evidence of mRCC, with treatment incorporating CN.
Patients receiving presurgical systemic targeted therapy prior to CN were compared to those undergoing immediate CN.
Complications were assessed using the modified Clavien system for a period of 12 mo postoperatively.
Presurgical therapy was administered to 70 patients prior to CN (presurgical), while 103 patients had an immediate CN (immediate). A total of 232 complications occurred in 57% of patients (99 of 173). Use of presurgical systemic targeted therapy was predictive of having a complication>90 d postoperatively (p=0.002) and having multiple complications (p=0.013), and it was predictive of having a wound complication (p<0.001). Despite these specific complications, presurgical systemic targeted therapy was not associated with an increased overall complication risk on univariable or multivariate analysis (p=0.064 and p=0.237) and was not predictive for severe (Clavien ≥3) complications (p=0.625). This study is limited by its retrospective nature. As is inherent to any retrospective study reporting on complications, we are limited by reporting bias and the potential for misclassification of specific complications.
Despite an increased risk for specific wound-related complications, overall surgical complications and the risk of severe complications (Clavien ≥3) are not greater after presurgical targeted therapy in comparison to upfront cytoreductive surgery.
European urology 05/2011; 60(5):964-71. · 7.67 Impact Factor
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ABSTRACT: This study was designed to evaluate the impact of tyrosine kinase inhibitors (TKIs) on incidence of brain metastasis (brain metastasis) and overall survival (OS) in patients with metastatic renal cell cancer (mRCC).
All patients who presented with mRCC but no brain metastasis in the intervals 2002 to 2003 and 2006 to 2007 were identified using the institutional tumor registry. The following data were collected: age, sex, Fuhrman grade, disease sites, nephrectomy, systemic therapy including TKIs (sorafenib or sunitinib), Memorial Sloan-Kettering Cancer Center risk category, brain metastasis treatment, and vital status. Statistical analysis was performed using the Cox proportional hazards model and the Kaplan-Meier method.
Of the 338 patients who were identified; 154 (46%) were treated with a TKI before brain metastasis, and 184 (54%) were not. There were no significant differences in age, histology, nephrectomy, involved sites of disease other than lung, or Memorial Sloan-Kettering Cancer Center risk category between the groups. Median OS was longer in the TKI-treated group (25 months vs 12.1 months, P < .0001). In multivariate analysis, TKI treatment (hazard ratio [HR], 0.53; 95% confidence interval [CI], 0.38-0.74; P < .001) was associated with improved OS. Forty-four (13%) patients developed a brain metastasis, including 29 (15.8%) of the non-TKI group and 15 (9.7%) of the TKI group. The 5-year actuarial rate of brain metastasis was 40% versus 17%, respectively (P < .001). TKI treatment was associated with lower incidence of brain metastasis in Cox multivariate analysis (HR, 0.39; 95% CI, 0.21-0.73; P = .003). Lung metastasis increased the risk of brain metastasis (HR, 9.61; 95% CI, 2.97-31.1; P < .001).
Treatment with TKI agents reduces the incidence of brain metastasis in mRCC. Lung metastasis is a risk factor for brain metastasis development.
Cancer 04/2011; 117(21):4958-65. · 4.77 Impact Factor
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Current Oncology Reports 04/2011; 13(3):153-6. · 2.55 Impact Factor
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ABSTRACT: • To investigate the effect of combining gemcitabine plus capecitabine (GX) with bevacizumab (A) in patients with metastatic RCC previously treated with cytokines and targeted agents.
• The combination of GX + A was evaluated in patients with metastatic RCC using institutional databases. • Data included demographics, previous therapies, number of metastatic sites, Memorial Sloan-Kettering Cancer Center risk stratification variables, and previous nephrectomy status. • Descriptive statistics and survival analysis were employed for data analysis.
• Between January 2005 and October 2008, 28 patients were identified. Mean age was 55.7 years. Fifteen (53.57%) patients had been given tyrosine kinase inhibitor (TKI) previously. Nine (32.14%) patients had clear cell histology, 10 (35.71%) patients had sarcomatoid features on histopathology, and 19 patients (67.86%) had a prior nephrectomy. • Initial treatment consisted of G (mean dose 786.07 mg/m²) every 2 weeks, X (mean dose 2.73 g/day), and A (mean dose 10 mg/kg) every 2 weeks. Median progression-free survival (PFS) was 5.9 months and the median overall survival (OS) was 10.4 months. • In patients with previous TKI therapy, median PFS was 6.2 months and median OS was 11.7 months. • In patients with sarcomatoid features, median PFS was 3.9 months and OS was 9.0 months. • Three patients discontinued one or more of the drugs because of adverse reactions.
• The combination of GX + A shows potential efficacy and acceptable tolerability in patients with intermediate and poor prognosis metastatic RCC. • Based on these observations, a phase II trial is now underway assessing this combination in patients with sarcomatoid RCC.
BJU International 03/2011; 107(5):741-7. · 2.84 Impact Factor
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Jose A Karam,
Brian I Rini,
Leticia Varella,
Jorge A Garcia,
Robert Dreicer,
Toni K Choueiri, Eric Jonasch,
Surena F Matin,
Steven C Campbell,
Christopher G Wood,
Nizar M Tannir
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ABSTRACT: Metastasectomy is often incorporated in overall treatment in patients with metastatic renal cell carcinoma. While this approach was studied in the immunotherapy era, only a few cases have been described in the targeted therapy era. Thus, we evaluated the role of metastasectomy in patients with metastatic renal cell carcinoma who received prior targeted therapy.
We retrospectively evaluated the records of patients who underwent consolidative metastasectomy after targeted therapy at 3 institutions from 2004 to 2009. All patients received at least 1 cycle of targeted therapy before surgical resection of all visible disease.
We identified 22 patients. Metastasectomy sites included the retroperitoneum in 12 patients, lung in 6, adrenal gland in 2, bowel in 2, and mediastinum, bone, brain and inferior venal caval thrombus in 1 each. A total of 6 postoperative complications were observed in 4 patients within 12 weeks after surgery, which resolved with appropriate management. Postoperatively 9 patients received at least 1 targeted therapy. In 11 patients recurrence developed a median of 42 weeks after metastasectomy and another 11 experienced no recurrence at a median of 43 weeks. At a median followup of 109 weeks 21 patients were alive and 1 died of renal cell carcinoma 105 weeks after metastasectomy.
In a cohort of select patients with a limited tumor burden after treatment with targeted agents consolidative metastasectomy is feasible with acceptable morbidity. Significant time off targeted therapy and long-term tumor-free status are possible with this approach.
The Journal of urology 02/2011; 185(2):439-44. · 4.02 Impact Factor
