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Christopher G Wood

Publications and source records attributed to Christopher G Wood.

At least 19 recordsLinked to original sources
PubMed2006

Treatment of patients with metastatic renal cell cancer: a RAND Appropriateness Panel.

BACKGROUND: New developments in the treatment of patients with metastatic renal cell cancer (MRCC) have suggested a need to reevaluate the role of systemic therapies. The authors convened a panel of medical and urologic oncologists to rate the appropriateness of the main options. METHODS: The authors used the RAND/University of California-Los Angeles Appropriateness Method to evaluate systemic therapy options and cytoreductive nephrectomy. After a comprehensive literature review, an expert panel rated the appropriateness of systemic options (108 permutations) and cytoreductive nephrectomy (24 permutations) for patients with MRCC. RESULTS: The appropriateness evaluation indicated that 27.3% of permutations were rated "appropriate," 46.9% were rated "inappropriate," and 25.8% were rated "uncertain." There was a high rate of agreement (95%). Sunitinib and sorafenib were rated appropriate for patients with low-to-moderate risk regardless of prior treatment. Temsirolimus was rated appropriate for first-line therapy for higher risk patients. Interferon-alpha and low-dose interleukin-2 were rated inappropriate or uncertain. In patients who received prior immunotherapy, cytokines were rated inappropriate. In all permutations for evaluating systemic therapy, enrollment into an investigational trial was considered appropriate, treatment with bevacizumab was uncertain, and thalidomide was inappropriate regardless of risk status or prior therapy. For good surgical risk patients with planned immunotherapy, nephrectomy was rated appropriate in patients who had limited metastatic burden regardless of tumor-related symptoms and in symptomatic patients regardless of metastatic burden. Only the most favorable combination of surgical risk, metastatic burden, and symptoms generated an "appropriate" rating for patients with planned targeted therapy. CONCLUSIONS: The current results begin the process of defining an appropriate role for cytokines, newer targeted therapies, and surgery in the treatment of MRCC.

Carcinoma, Renal Cell↗
PubMed2006

Laparoscopic cytoreductive nephrectomy: the M. D. Anderson Cancer Center experience.

OBJECTIVES: Cytoreductive nephrectomy (CN) is an integral component in treating patients with metastatic renal cell carcinoma. Critics of CN argue that perioperative morbidity or postoperative disease progression may preclude patients from receiving systemic therapy. Laparoscopic cytoreductive nephrectomy (LCN) may allow for reduced morbidity and may increase the likelihood of patients receiving systemic therapy. METHODS: From April 2001 to March 2005, 38 patients underwent LCN at our institution. We evaluated perioperative parameters such as demographics, blood loss, operative time, complications, follow-up time, interval to systemic therapy, and survival. A contemporary open cytoreductive surgery group was evaluated for comparison. RESULTS: The median patient age was 62 years (range 41 to 82). Most patients had a performance status of 1 or less. The median operative time was 188 minutes, and the median blood loss was 175 mL. All specimens were removed intact. The median tumor size was 8 cm (range 3.5 to 14). The median hospitalization was 3 days. Two major (5.7%) and four minor (11.4%) complications occurred, but no perioperative mortality. Postoperatively, 97.4% of patients were eligible for, or received, systemic therapy at a median of 41 days. The overall median survival was 18.1 months. In contrast to open CN, LCN resulted in decreased blood loss and hospital stay, with no differences in complications, operative time, or interval to systemic therapy. CONCLUSIONS: LCN is a safe and effective surgical approach for select patients with metastatic renal cell carcinoma. Our results have indicated that with proper patient selection, LCN is feasible, morbidity is minimized, and systemic therapy is delivered in a timely fashion.

Adult↗
PubMed2006

Lymphocyte activation antigen CD70 expressed by renal cell carcinoma is a potential therapeutic target for anti-CD70 antibody-drug conjugates.

Metastatic renal cell carcinoma (RCC) is an aggressive disease refractory to most existing therapeutic modalities. Identifying new markers for disease progression and drug targets for RCC will benefit this unmet medical need. We report a subset of clear cell and papillary cell RCC aberrantly expressing the lymphocyte activation marker CD70, a member of the tumor necrosis factor superfamily. Importantly, CD70 expression was found to be maintained at the metastatic sites of RCC. Anti-CD70 antibody-drug conjugates (ADC) consisting of auristatin phenylalanine phenylenediamine (AFP) or monomethyl auristatin phenylalanine (MMAF), two novel derivatives of the anti-tubulin agent auristatin, mediated potent antigen-dependent cytotoxicity in CD70-expressing RCC cells. Cytotoxic activity of these anti-CD70 ADCs was associated with their internalization and subcellular trafficking through the endosomal-lysosomal pathway, disruption of cellular microtubule network, and G2-M phase cell cycle arrest. The efficiency of drug delivery using anti-CD70 as vehicle was illustrated by the much enhanced cytotoxicity of antibody-conjugated MMAF compared with free MMAF. Hence, ADCs targeted to CD70 can selectively recognize RCC, internalize, and reach the appropriate subcellular compartment(s) for drug release and tumor cell killing. In vitro cytotoxicity of these ADCs was confirmed in xenograft models using RCC cell lines. Our findings provide evidence that CD70 is an attractive target for antibody-based therapeutics against metastatic RCC and suggest that anti-CD70 ADCs can provide a new treatment approach for advanced RCC patients who currently have no chemotherapeutic options.

Animals↗
PubMed2006

Chylous ascites after post-chemotherapy retroperitoneal lymph node dissection: review of the M. D. Anderson experience.

PURPOSE: We determined the clinical presentation, risk factors and optimal treatment of chylous ascites that develop after retroperitoneal lymph node dissection in patients with testicular cancer. MATERIALS AND METHODS: We retrospectively reviewed the records of 329 patients who underwent post-chemotherapy retroperitoneal lymph node dissection at our institution, of whom 23 (7%) had chylous ascites postoperatively. Clinical and pathological parameters were entered into a database. RESULTS: Mean patient age at chylous ascites presentation was 32.1 years. On univariate and multivariate logistic regression analyses increasing amounts of preoperative chemotherapy (OR 1.24) and intraoperative blood loss (OR 1.33) were predictive of chylous ascites. The clinical presentation of chylous ascites consisted of abdominal fullness and distention in all patients. Initial treatment was paracentesis alone or combined with total parenteral nutrition in 77% of patients. An abdominal drain was used for persistent ascites in 10 patients. In patients treated conservatively the rate of resolution of chylous ascites was 77%. Only 23% of patients required peritoneovenous shunt placement. However, shunt use was associated with an 80% surgical revision rate. CONCLUSIONS: Conservative treatment resolves most cases of postoperative chylous ascites. An abdominal catheter drain should be considered for significant or recurring chylous ascites. When a peritoneovenous shunt is required, it may be needed for an extensive period for resolution and there are significant complications associated with its use. Increasing amounts of preoperative chemotherapy and operative blood loss raise the likelihood of chylous ascites.

Adult↗
PubMed2006

Renal cell carcinoma with nodal metastases in the absence of distant metastatic disease (clinical stage TxN1-2M0): the impact of aggressive surgical resection on patient outcome.

PURPOSE: Nodal disease in the setting of metastatic renal cell carcinoma is associated with poor prognosis. However, to our knowledge the biology of nodal metastases in the absence of metastatic disease is unknown. We reviewed our experience with treating this subset of patients with aggressive surgical resection. MATERIALS AND METHODS: A total of 2,643 patients underwent nephrectomy at our institution between 1993 and 2003, including 40 with positive lymph nodes but no systemic metastases. All 40 patients underwent nephrectomy with extended retroperitoneal lymphadenectomy and they are the subjects of this study. Pathological characteristics and clinical outcomes were assessed. RESULTS: Median patient age was 58 years and 62% of the patients were male. Median tumor size was 11 cm. Local stage was T1 in 3% of cases, T2 in 17%, T3a in 30%, T3b in 47% and T4 in 3%. Perinephric fat invasion was present in 77% of patients and positive margins were identified in 17%. Nodal status was N1 in 30% of patients and N2 in 70%, including 10 with masses of matted nodes. Histology was conventional in 63% of cases and papillary in 17%. The remaining 20% of patients had sarcomatoid dedifferentiation. Excluding the 10 patients with matted nodes the median number of nodes harvested per patient was 7 with a median of 2 that were positive. Extranodal extension was present in 70% of cases, while in 70% disease recurred at a median of 4.9 months. Median actuarial disease specific survival was 20.3 months. At a median followup of 17.7 months 30% of patients had no evidence of disease, 8% had disease and 62% had died. On multivariate analysis more than 1 positive node was predictive of decreased recurrence-free survival (HR 2.83, 95% CI 1.06 to 7.61, p = 0.039) and overall survival (HR 9.33, 95% CI 1.85 to 47.09, p = 0.007). CONCLUSIONS: Nodal metastasis with renal cell carcinoma is an independent predictor of prognosis in patients with M0 disease. Even in the absence of distant metastatic disease patients with positive nodes should be targeted for aggressive surgical resection, followed by clinical trials of adjuvant therapy to improve the outcome.

Adolescent↗
PubMed2006

Adjuvant therapy for renal cell carcinoma.

In 2006, approximately 38,890 patients in the United States will be diagnosed with kidney tumors. Roughly 90% of those will be renal cell carcinomas (RCCs). Of those patients, 30% will have metastatic disease at the time of diagnosis. An additional 20% to 30% with clinically localized disease at the time of nephrectomy will subsequently develop metastatic disease for which there are few reliable, effective treatments. In 2006, no clinically proven, adjuvant therapy exists for patients at high risk of relapse following definitive surgical therapy. In the past, several strategies have been tried unsuccessfully in the adjuvant setting, including, radiotherapy, chemotherapy, immunotherapy, and hormonal therapy. An improved understanding of the molecular basis of RCC has allowed for a more targeted approach to therapy. Several newer agents, including thalidomide, vitespin (heat shock protein [hsp] 96 vaccine), WX-G250, sorafenib, and sunitinib, are either currently under investigation in the adjuvant setting or being considered for future adjuvant trials. Here, we discuss the past, present, and future of adjuvant therapy for RCC patients at high risk for relapse following definitive surgical therapy.

Antineoplastic Agents↗
PubMed2006

Conventional and hand-assisted laparoscopic radical nephrectomy: Comparative analysis of 271 cases.

PURPOSE: To compare the outcomes of patients undergoing conventional laparoscopic radical nephrectomy (CLRN) and hand-assisted laparoscopic radical nephrectomy (HALRN) at our institution. PATIENTS AND METHODS: We prospectively and retrospectively reviewed the files of consecutive patients who underwent HALRN (N = 158 patients) from April 2001 to May 2005 and CLRN (N = 113) from August 2002 to May 2005 for clinical stage T(1-3)N(0-1)M(0-1) renal-cell carcinoma. Clinical and perioperative variables of the two groups were compared. Patients were well matched with regard to baseline parameters except that patients undergoing CLRN were 8 years older (P < 0.001) and had higher American Society of Anesthesiologists scores (P = 0.001). RESULTS: Significantly different outcomes were faster operative time (P < 0.001), greater use of narcotic analgesia (P < 0.001), and longer hospitalization (P < 0.001) with HALRN. For the other variables analyzed, including blood loss, incision size, and complication rates, the two approaches were not significantly different. CONCLUSIONS: Within the limitations of a retrospective study, HALRN was a faster operation than CLRN but was associated with greater use of narcotic analgesia and longer hospitalization. Overall, the similarities between these two approaches outnumber the differences, some of which may be explained by surgeon-specific practices. Both modalities offer patients excellent immediate cancer control while minimizing perioperative morbidity.

Adult↗
PubMed2006

Staging refinements in renal cell carcinoma.

PURPOSE OF REVIEW: Accurate pathologic staging systems provide valuable prognostic information. As our understanding of the biology of renal cell carcinoma improves, so does the staging system has undergo periodic modification. The modification of the tumor-node-metastasis staging system in 2002 has been applied to various populations, and several changes have been proposed. RECENT FINDINGS: The tumor diameter chosen as a break point in the staging system for noninvasive tumors is debated. Although 4 cm, the break point between T1a and T1b tumors, was chosen, in part, to select tumors amenable to partial nephrectomy, newer data show that this may no longer be appropriate. Size appears to have continual prognostic significance, especially in the range of 4-6 cm. T3a tumors with adrenal involvement appear to have a poor prognosis similar to T4 tumors. In addition, while renal sinus invasion may have a worse prognosis, perinephric fat invasion appears to have less impact on survival than overall tumor size. SUMMARY: Refinements of the current staging system on the basis of current understanding of tumor characteristics will improve prognostic accuracy. The addition of molecular markers and other features should be considered while not allowing increased complexity to disrupt clinical utility.

Carcinoma, Renal Cell↗
PubMed2006

Nephroureterectomy for treating upper urinary tract transitional cell carcinoma: Time to change the treatment paradigm?

OBJECTIVE: To evaluate factors associated with disease recurrence and survival in patients undergoing nephroureterectomy for upper urinary tract transitional cell carcinoma (UUT-TCC) in one centre over an 18-year period. PATIENTS AND METHODS: The records of patients who had a nephroureterectomy for UUT-TCC at our institution from 1986 to 2004 were reviewed for clinical, pathological and treatment period data. Cox's proportional hazards regression model was used to test the statistical significance of several potential prognostic factors for recurrence and survival. RESULTS The median overall duration of follow-up was 2.5 years for 184 patients. Significant prognosticators for disease-specific survival (DSS) by univariate analysis were tumour stage (P < 0.01), tumour grade (P < 0.01), node-positive disease (P < 0.01), multifocality (P = 0.03), previous cystectomy (P < 0.01) and synchronous bilateral UUT-TCC (P = 0.02). On multivariate analysis, only tumour stage (P = 0.03) and grade (P = 0.01) correlated with DSS. The median recurrence-free survival duration was 2.4 years. In 44 patients, the disease recurred outside the bladder; 15 (8.2%) had local recurrence, 20 (10.9%) distant metastasis, and nine (4.9%) both local and distant recurrence. Bladder tumours occurred in 40 (26.1%) patients with no previous cystectomy. The evaluation of treatment outcome during three periods of the study showed no significant effect on DSS. CONCLUSION: Tumour stage and grade correlated with DSS in this cohort, with no improvement in outcome over the 18-year period assessed. Patients with high-stage and high-grade disease continue to fare poorly, suggesting a need for changing the treatment protocol. Judiciously applying a multimodal approach to the management of high-risk patients by incorporating neoadjuvant chemotherapy and surgical resection might provide, for the first time, the opportunity to improve patient outcome.

Aged↗
PubMed2005

Bcl-2 antisense oligonucleotide overcomes resistance to E1A gene therapy in a low HER2-expressing ovarian cancer xenograft model.

We are currently conducting clinical trials of E1A gene therapy for patients with ovarian cancer. The adenovirus type 5 E1A gene suppresses growth of ovarian cancer cells that overexpress HER-2/neu (HER2) and growth of some--but not all--that express low HER2. In HER2-overexpressing cells, suppression by E1A is predominantly by down-regulation of HER2, but the mechanism in low HER2-expressing cells is not fully understood. The adenoviral E1B protein has sequential and functional homology to Bcl-2 and prolongs the viability of adenovirus host cells by inhibiting E1A-induced apoptosis. Bcl-2 is overexpressed in ovarian cancer and participates in chemoresistance; we hypothesized that Bcl-2 inhibits E1A-induced apoptosis leading to resistance to E1A gene therapy. E1A suppressed colony formation of ovarian cancer cells that express low levels of Bcl-2 and HER2 (OVCAR-3 and OVCA 433), but enhanced colony formation in low HER2-, high Bcl-2-expressing ovarian cancer cells (2774 and HEY). Treating 2774 or HEY cells with antisense oligonucleotide Bcl-2 (Bcl-2-ASO) did not reduce cell viability. E1A combined with Bcl-2-ASO led to significant decreases in cell viability resulting from increased apoptosis relative to cells treated with E1A alone (P < 0.05). The increase in apoptosis was partly due to cytochrome c release and subsequently caspase-9 activation by Bcl-2-ASO. Finally, in an ovarian cancer xenograft model, treatment with Bcl-2-ASO did not prolong survival, but E1A plus Bcl-2-ASO did (P < 0.001). In conclusion, ovarian tumors overexpressing Bcl-2 may not respond well to E1A gene therapy, but treatment with a combination of E1A and Bcl-2-ASO may overcome this resistance.

Adenovirus E1B Proteins↗
PubMed2005

Prognostic value of histologic subtypes in renal cell carcinoma: a multicenter experience.

PURPOSE: To analyze to what extent histologic subtype is of prognostic importance in renal cell carcinoma based on a large, international, multicenter experience. PATIENTS AND METHODS: Four thousand sixty-three patients from eight international centers were included in this retrospective study. Histologic subtype (1997 International Union Against Cancer [UICC] criteria of tumor response), age, sex, TNM stage, Fuhrman grade, tumor size, Eastern Cooperative Oncology Goup performance status (ECOG PS), and overall survival were determined in all cases. The prognostic values of clear cell, papillary, and chromophobe histologic features were assessed by uni- and multivariate analysis using the Kaplan-Meier method and Cox model, respectively. RESULTS: Clear cell, papillary, and chromophobe carcinomas accounted for 3,564 (87.7%), 396 (9.7%) and 103 (2.5%) cases, respectively. In univariate analysis, a trend toward a better survival was observed when clear cell, papillary, and chromophobe histologies were considered prognostic categories (log-rank P = .0007). However, in multivariate analysis, TNM stage, Fuhrman grade and ECOG PS, but not histology, were retained as independent prognostic variables (P < .001). CONCLUSION: The stratification in three main renal cell carcinoma histologic subtypes as defined by the 1997 UICC-American Joint Committee on Cancer consensus should not be considered a major prognostic variable comparable to TNM stage, Fuhrman grade and ECOG PS.

Adolescent↗
PubMed2005

Evaluation of the intact specimen after laparoscopic radical nephrectomy for clinically localized renal cell carcinoma identifies a subset of patients at increased risk for recurrence.

PURPOSE: Laparoscopic radical nephrectomy (LRN) is emerging as a standard approach for low stage renal cell carcinoma (RCC). Some suggest that specimen morcellation for extraction results in less morbidity and a faster recovery. However, morcellation may preclude accurate pathological staging and may hinder precise pathological grading. With pathological evaluation of an intact specimen we identified patients harboring high risk disease that was not anticipated preoperatively, defined as pT2 high grade (G3-4) or lesions greater than pT2. MATERIALS AND METHODS: We retrospectively reviewed the records of 192 patients who underwent LRN for renal lesions at The University of Texas M. D. Anderson Cancer Center between April 2002 and April 2004. RESULTS: A total of 192 patients underwent LRN for presumed RCC. In all cases specimens were removed intact. Of these cases 137 were cT1/T2 N0 M0 and had a final pathological diagnosis of RCC. All surgical margins were negative. Of the 137 patients 40 (29.2%) were at increased risk for recurrence based on high risk features. Specifically up staging from cT1-2 to pT3 disease occurred in 30 patients (21.9%) while 12 patients (8.8%) were found to have pT2 G3-4 disease. All 40 patients with high risk disease underwent more intensive surveillance and 17 (43%) participated in adjuvant systemic therapy trials. CONCLUSIONS: In our study 21.9% of patients with clinical T1-2 disease were pathologically up staged and 29.2% were identified as being at high risk for recurrence after intact specimen extraction for localized RCC. These patients are candidates for more intensive followup treatment and may benefit from enrollment in adjuvant therapy protocols.

Carcinoma, Renal Cell↗
PubMed2005

Percutaneous radiofrequency ablation of renal tumors: technique, complications, and outcomes.

PURPOSE: To report the safety, technical success, and effectiveness of percutaneous radiofrequency (RF) ablation for renal tumors. MATERIALS AND METHODS: The authors retrospectively reviewed the medical records and imaging studies of 29 consecutive patients (18 men, 11 women; mean age, 65 +/- 2.62 years) with 30 renal tumors (mean diameter, 3.5 +/- 0.24 cm) who underwent percutaneous RF ablation at their institution from September 2001 to March 2004. All procedures were performed with computed tomography guidance with general anesthesia, and all patients were admitted to the hospital for overnight observation. Technical success, complications, and their management were recorded. Technique effectiveness was assessed by imaging and clinical follow up. RESULTS: Overall, 88 overlapping ablations were performed (mean, 2.6 +/- 0.16 ablations per tumor per session) in 34 sessions. There were four major complications (12%). Three patients had gross hematuria and urinary obstruction, all were successfully treated. One patient had persistent anterior abdominal wall weakness. There were also two minor complications (6%) without significant clinical sequelae. One patient had gross hematuria which resolved spontaneously, another patient had transient paresthesia of the anterior abdominal wall. There were no significant changes in renal function after RF ablation. The intent of RF ablation was eradication of the primary tumor in 27 patients and treatment of gross hematuria in the other two. Technical success was achieved in all cases. Follow-up images were available for 26 patients. The primary tumor was completely ablated in 23 of 24 patients (96%) in whom eradication of the primary tumor was attempted (follow up period: mean, 10 months, median 7 months). The two patients treated for hematuria remained asymptomatic for 6 and 27 months each. CONCLUSION: Percutaneous RF ablation for renal tumors is safe and well tolerated. High technical success rates are expected. Early reports of the technique's effectiveness are promising.

Adult↗
PubMed2005

Changes in serum proteomic patterns by presurgical alpha-tocopherol and L-selenomethionine supplementation in prostate cancer.

BACKGROUND: Evidence of the chemopreventive effects of the dietary antioxidants alpha-tocopherol (vitamin E) and l-selenomethionine (selenium) comes from secondary analysis of two phase III clinical trials that found treatment with these antioxidants reduced the incidence of prostate cancer. To determine the effects of selenium and vitamin E in blood and prostate tissue, we undertook a preoperative feasibility study complementary to the currently ongoing Selenium and Vitamin E Cancer Prevention Trial. METHODS: Forty-eight patients with clinically localized prostate cancer enrolled on this 2 x 2 factorial design study were randomized to take selenium, vitamin E, both, or placebo for 3 to 6 weeks before prostatectomy. Sera were collected from patients before and after dietary supplementation. Thirty-nine patients were evaluable, and 29 age-matched disease-free men served as controls. Mass profiling of lipophilic serum proteins of lower molecular weight (2-13.5 kDa) was conducted, and mass spectra data were analyzed using custom-designed software. RESULTS: Weighted voting analyses showed a change in sera classification from cancerous to healthy for some patients with prostate cancer after dietary intervention. ANOVA analysis showed significantly different treatment effects on prediction strength changes among the four groups at a 95% confidence level. Eliminating an outlying value and performing post hoc analysis using Fisher's least significant difference method showed that effects in the group treated with the combination were significantly different from those of the other groups. CONCLUSION: In sera from patients with prostate cancer, selenium and vitamin E combined induced statistically significant proteomic pattern changes associated with prostate cancer-free status.

Analysis of Variance↗
PubMed2004

A renal mass in the setting of a nonrenal malignancy: When is a renal tumor biopsy appropriate?

BACKGROUND: Frequently, a renal mass is identified when patients with cancer undergo studies for staging or surveillance. In determining whether it represents a metastasis, patients are frequently subjected to percutaneous renal biopsies. The authors evaluated their experience with this dilemma to formulate management guidelines. METHODS: The authors reviewed the medical records of 100 consecutive patients with nonrenal malignancies diagnosed with renal masses at presentation or follow-up. Renal mass histology was available for all patients after nephrectomy or biopsy. Clinical characteristics were assessed to identify factors predictive for a renal metastasis versus a primary renal neoplasm. RESULTS: The only factors predictive of a metastasis to the kidney were progression of the nonrenal malignancy and lack of enhancement of the renal mass (P < 0.0001). Forty-six patients (46%) had evidence of progression of their nonrenal malignancy in addition to the renal mass. In these patients, the probability of a metastasis to the kidney was 86% (95% confidence interval [CI], 57.2-98.2%) without renal mass enhancement and 32% (95% CI, 14-55%) with enhancing renal masses. None of the 54 patients without signs of progression of their nonrenal malignancy proved to have metastases to the kidney, regardless of the imaging characteristics of the mass (zero probability; 95% CI, 0-7%; P < 0.001). CONCLUSIONS: In patients presenting with renal masses and another clinically localized malignancy, renal mass biopsies were not indicated, as the mass rarely represented a metastasis. These patients may opt for close surveillance or extirpation based on the prognosis of their nonrenal malignancy.

Adult↗
PubMed2004

Use of the University of California Los Angeles integrated staging system to predict survival in renal cell carcinoma: an international multicenter study.

PURPOSE: To evaluate ability of the University of California Los Angeles Integrated Staging System (UISS) to stratify patients with localized and metastatic renal cell carcinoma (RCC) into risk groups in an international multicenter study. PATIENTS AND METHODS: 4,202 patients from eight international academic centers were classified according to the UISS, which combines TNM stage, Fuhrman grade, and Eastern Cooperative Oncology Group performance status. Distribution of the UISS categories was assessed in the overall population and in each center. RESULTS: The UISS stratified both localized and metastatic RCC into three different risk groups (P <.001). For localized RCC, the 5-year survival rates were 92%, 67%, and 44% for low-, intermediate-, and high-risk groups, respectively. A trend toward a higher risk of death was observed in all centers for increasing UISS risk category. For metastatic RCC, the 3-year survival rates were 37%, 23%, and 12% for low-, intermediate-, and high-risk groups, respectively; in 6 of 8 centers, a trend toward a higher risk of death was observed for increasing UISS risk category. A greater variability in survival rates among centers was observed for high-risk patients. CONCLUSION: This study defines the general applicability of the UISS for predicting survival in patients with RCC. The UISS is an accurate predictor of survival for patients with localized RCC applicable to external databases. Although the UISS may be useful for patients with metastatic RCC, it may be less accurate in this subset of patients due to the heterogeneity of patients and treatments.

Adult↗
PubMed2004

Evidence that transfer of functional p53 protein results in increased apoptosis in prostate cancer.

PURPOSE: INGN 201 (Ad-p53) is a replication-defective adenoviral vector that encodes a wild-type p53 gene driven by the cytomegalovirus promoter. INGN 201 has been shown to have antitumoral activity against human prostate cancer cell lines. This study was undertaken to determine the safety of INGN 201 in patients with locally advanced prostate cancer, to assess transgene expression, and to evaluate antitumoral activity. EXPERIMENTAL DESIGN: Our study included patients with clinical stage T3, T1c-T2a with Gleason score 8-10 disease, or T2a-T2b with Gleason score 7 disease and a prostate-specific antigen level >10 ng/ml. INGN 201 was administered by intraprostatic injection under ultrasonographic guidance. One course of INGN 201 was defined as three separate INGN 201 administrations 2 weeks apart. Biopsies at baseline and 24 h after the first administration were assessed for p53 protein by immunohistochemical staining and for apoptosis by terminal deoxynucleotidyl transferase-mediated nick end labeling assay. RESULTS: A total of 38 courses of INGN 201 gene therapy were administered to 30 patients, of whom 26 underwent radical prostatectomy. There were no grade 3 or 4 adverse events related to INGN 201 administration. Of the 11 patients with negative baseline immunostaining for p53 protein, 10 had positive p53 immunostaining after the first administration of INGN 201, and 8 had an increase in apoptotic cells by terminal deoxynucleotidyl transferase-mediated nick end labeling staining. All 26 of the patients who underwent radical prostatectomy had significant residual viable prostate cancer, and 12 have experienced biochemical failure (median follow-up, 42 months). CONCLUSION: Intraprostatic INGN 201 gene therapy is safe and can reliably result in p53 protein production and apoptosis.

Adenoviridae↗