Memorial Sloan-Kettering Cancer Center Criteria Research Articles

Influence of Prognostic Group Classification of Advanced Male Germ Cell Tumor on Treatment Outcomes

Background: Male germ cell tumor is a rare disease, associated with high rates of cure, including in the advanced setting. This disease mostly affects young males aged 15-34 years. The rising incidence trends of germ cell tumors in the last two decades have defined a new priority area of oncology. Objective: To investigate the influence of prognostic group classification and histology on treatment outcomes in men treated in a single institution in Pakistan. Methods: We developed an observational study on fifty male patients diagnosed with advanced germ cell cancer completing first-line treatment, between 2011-2014. Patients with a follow-up time of at least 5 years post-treatment were included. Patients were classified into good, intermediate, and poor prognostic groups, according to the International Germ Cell Cancer Collaborative Group classification (IGCCCG). The outcomes of all three prognostic groups were measured including response to first-line treatment according to Memorial Sloan-Kettering Cancer Center criteria and five years OS. Survival rates were calculated using Kaplan and Meier method. The level of significance was set at P < 0.05. Results: Overall 50 patients were included in the study. The mean age of patients was 30.6 years + 9.49 years. The most common primary site of involvement was the right testicle i.e.56.0%. Complete responses (CR) were observed in 23 (46.0%) patients. The patients classified into the good prognostic group (n=29) had significantly superior (p=0.002) five years OS (86.2%, n= 25) than intermediate and poor groups. Additionally, CR was higher for seminoma-type cancer i.e. 12 (63.15%) while it was limited to 11(35.48%) in non-seminoma; however, the inferior response rate in NSGCT did not translate into statistical significance in 5 years OS. Conclusion: The IGCCCG prognostic grouping system is an effective tool for predicting treatment outcomes in terms of 5-year overall survival in our local population based in a low-middle income setting.

The difference in the survival rate of patients with metastatic renal cell carcinoma in the intermediate-risk group of the Memorial Sloan Kettering Cancer Center criteria.

ObjectivesTo investigate the necessity of stratifying patients in the intermediate-risk group of the Memorial Sloan Kettering Cancer Center (MSKCC) criteria in a real-world population of patients with metastatic renal cell carcinoma.Patients and MethodsWe retrospectively analyzed 234 consecutively treated patients who had received molecular targeted drugs. We examined the difference between progression-free survival and overall survival among patients in the intermediate-risk group of MSKCC criteria. We divided the intermediate group into two subgroups as follows: patients positive for only one risk factor (Int-1) and those positive for two risk factors (Int-2) including performance status, serum hemoglobin level, time from diagnosis to treatment, and corrected calcium and lactate dehydrogenase levels. Next, we evaluated the association between the number of metastatic organs, the presence of pancreatic metastasis, Int-1 or Int-2 grouping, and overall survival.ResultsThe median overall survival was 41.2 months. The median overall survival of the favorable-, intermediate-, and poor-risk groups of the MSKCC criteria were 91.0, 33.6, and 15.2 months, respectively. Patient characteristics were similar between the Int-1 and Int-2 groups. Increased positivity for risk factors of MSKCC classification between the two groups was for performance status and serum hemoglobin level. Progression-free survival and overall survival of the Int-1 group were significantly higher than those of the Int-2 group. In Cox proportional stepwise multivariate analysis, the Int-1 and Int-2 classification was an independent risk factor for overall survival.ConclusionPatients in the intermediate-risk group had different prognoses depending on the number of positive risk factors.

Oncological outcomes classified according to metastatic lesions in the era of molecular targeted drugs for metastatic renal cancer.

Since the introduction of molecular targeted agents for the treatment of metastatic renal cell cancer (mRCC), several treatment outcomes, including those from our facilities, have been reported. However, the outcome of these drugs, classified by the metastatic organs, is not well known. The present study reported the treatment results of molecular-targeted agents as classified by the metastatic organ at Osaka City University Graduate School of Medicine. A total of 180 consecutively treated patients who had received molecular targeted agents for metastatic renal cancer for 3 or more months were retrospectively analyzed. The overall survival was calculated and compared according to the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria, the number of metastatic organs, and metastatic lesions. The median overall survival of patients with mRCC treated by molecular targeted agents was 34 months. A significant difference in survival rate between groups was found according to the MSKCC criteria. Patients with single metastatic organ lived significantly longer compared with those with metastases in multiple organs. Patients with pancreatic metastasis had a good response to molecular targeted drugs. Pancreatic metastasis, the number of metastatic organs, and MSKCC criteria were independent risk factors for overall survival. Treatment of mRCC by molecularly targeted agents did not show any difference by metastatic organs except for the pancreas, although its efficacy depends on the number of metastatic organs and the MSKCC classification.

Targeted therapy in patients with poor-prognosis renal cell carcinoma

The majority of patients with metastatic renal cell carcinoma (mRCC) are in the groups of favorable or moderate prognosis per the MSKCC (MemorialSloan-KetteringCancerCenter) criteria, but in 20–30 % of poor-prognosis patients aggressive, rapidly progressing mRCC is observed. Despite improved prognosis in mRCC patients due to targeted therapy, this patient group remains hard to treat with overall survival 6 months) was higher in the temsirolimus (32.1 %) and combination (28.1 %) groups compared to the IFN-α group (15.5 %; р<0,001).

Pretreatment Prognostic Nutritional Index Is an Independent Predictor of Survival in Patients With Metastatic Renal Cell Carcinoma Treated With Targeted Therapy

BackgroundIn the present study we examined the effect of the Prognostic Nutritional Index (PNI) on the overall survival (OS) and progression-free survival (PFS) of patients with metastatic renal cell carcinoma (RCC) treated with targeted therapy. Patients and MethodsThe study included 125 patients with metastatic RCC. Pretreatment PNI was calculated as 10 × serum albumin (g/dL) + 0.005 × total lymphocyte count (per mm3). Univariable and multivariable Cox proportional hazards models were used to assess the correlation between pretreatment PNI and OS and PFS. Harrell concordance index was used to measure discrimination. ResultsThe median follow-up time was 45.3 months (interquartile range, 23.7-77.3 months). Decreased PNI was significantly associated with older female patients, poor Eastern Cooperative Oncology Group performance status, types of initial drug, and increased Memorial Sloan Kettering Cancer Center (MSKCC) and Heng risk score (P < .05). An increase in the PNI of 1 unit was associated with a 10% decrease in the risk of death from RCC (hazard ratio, 0.90; P < .001). In the multivariable analysis, the PNI was an independent prognostic factor for OS (P < .001). In intermediate-risk patients according to MSKCC and Heng risk criteria, OS was better in the high PNI group than in the low PNI group (P = .0136 and P = .0009, respectively). ConclusionPNI is an independent prognostic factor in patients with metastatic RCC treated with targeted therapy. When used as an adjunct, it increases the prognostic accuracy of established factors and could be a valuable tool for tailoring surveillance, patient counseling, and clinical trial design.

Böbrek Hücreli Karsinomlu Hastaların Demografik Özellikleri ve Tedavi Sonuçları: Tek Merkez Deneyimi

Objectives: The aim of the study was to evaluate demographic characteristics and treatment outcomes of patients with renal cell cancer. Materials and Methods: Data of 100 patients diagnosed with RCC at Ataturk Research and Education Hospital between the years 2005-2014 are analyzed retrospectively. Kaplan-Meier test were performed for survival analysis. Results: Median age of patients was 62 (25-89) and 40% of the population was over 65 years old. Sex ration (male/female) was 2/1. Radical nephrectomy was perfomed 64 % of patients also partial nephrectomy rate was 7%. Histopathologically, clear cell varient’s rate was 84 %. Most of the patients were stage 4 (55%) and the most common metastatic site was lung (34%). After the development of metastases, first line interferone (IFN) treatment was administered to 62 of patients and 49 of these took tirosine kinase inhibitor after IFN treatment. For all patients, median follow-up time was 24 months and median overall survival (OS) was 36 months. We determined that OS was 30 months and progression free survival (PFS) was 15 months among patients had recieved sunitinib. During sunitinib treatment, dose reduction was performed in 53.8% of the patients and treatment was interrupted in 36.6% of the patients. Fatigue (34.9%) and anemia (27.9%) were the most common grade 3-4 toxicities. In patients who used sunitinib, median PFS in the good, intermediate and poor risk patients according to Memorial Sloan Kettering Cancer Center (MSKCC) criteria respectively were 45, 15 and 6 months (p=0.05). In multivariate analysis, we found that age over 65 years (p=0.04), grade 3-4 tumors (p=0.05) and the poor risk according to MSKCC criteria (p=0,04) are associated with decreased overall survival. Conclusion: The majority of our patients were male, younger than 65 years and had advanced disease at diagnosis. The significantly improvement in survival has been observed between the nephrectomized and metastatic RCC patients who used sunitinib at our clinic.

The Evolution of Nephrectomy and Patient Characteristics in Metastatic Renal Cell Carcinoma Patients Enrolled Into First-Line Tyrosine Kinase Inhibitors Clinical Trials

IntroductionThe objective of this study was to compare rates of nephrectomy (Nx) in, and characteristics of, patients with metastatic renal cell carcinoma (mRCC) enrolled in prospective clinical trials of tyrosine kinase inhibitors (TKIs) that were completed through (Group 1) versus after (Group 2) 2007. Patients and MethodsSearching online databases, we retrospectively identified phase I to III trials with ≥ 15 patients with mRCC treated with first-line TKIs, alone or in combination with other agent(s). ResultsOf 70 trials identified, 42 were included in the analysis (n = 6074 patients). Compared with Group 1, Group 2 patients had significantly less Nx (85.7% vs. 93.7%; P < .001) and prior cytokine therapy (11.1% vs. 46.8%; P < .001). Group 2 also had significantly fewer patients with good prognostic risk (based on Memorial Sloan-Kettering Cancer Center criteria) or performance status (both P < .001). Group 2 patients had a significantly greater objective response rate than Group 1 patients (intent-to-treat analysis: 28.6% vs. 23.1%, respectively; P < .001), whereas Group 1 patients had significantly more stable disease. Clinical benefit was similar in both groups (P = .157), and the means of median progression-free survival were comparable (8.2 and 9.0 months in Groups 1 and 2, respectively; P = .2528). ConclusionsUse of Nx in mRCC patients participating in clinical trials has declined in the TKI era. More patients with worse prognostic risk profiles are participating in first-line TKI trials after 2007, but objective response rates are higher. Despite patient characteristics that favor the earlier group, progression-free survival is similar as TKIs have replaced cytokines as first-line therapy.

Bevacizumab Monotherapy as Salvage Therapy for Advanced Clear Cell Renal Cell Carcinoma Pretreated With Targeted Drugs

BackgroundBevacizumab has shown benefit in the first-line treatment of metastatic clear cell renal cell carcinoma (ccRCC) in combination with interferon α. In this retrospective analysis we assessed the efficacy of bevacizumab monotherapy in patients whose disease progressed during treatment with vascular endothelial growth factor (VEGF) receptor tyrosine kinase inhibitors, and/or mammalian target of rapamycin inhibitors. Patients and MethodsA retrospective analysis was performed on metastatic ccRCC patients who received bevacizumab monotherapy after their disease progressed during treatment with previous targeted therapies. The primary objective was to assess overall survival (OS) and the secondary objectives includes progression-free survival (PFS), therapy duration, and incidence of serious adverse events assessed during visits to the Memorial Sloan Kettering Cancer Center (MSKCC) urgent care center. ResultsSeventy-one patients were treated with bevacizumab as monotherapy in the salvage setting. Most patients were heavily pretreated with 36 patients (51%) who received bevacizumab as a fourth-line or later agent, and 33 patients (46%) who received at least 2 previous VEGF targeted agents. Eighteen patients (25%) had a Karnofsky Performance Status (KPS) < 80%, and 20 patients (28%) were classified as poor risk according to MSKCC criteria. Median OS was 11.5 months (95% confidence interval [CI], 6.4-17.4), and median PFS was 1.9 months (95% CI, 1.7-4.1). Nine patients (13%) had a prolonged time of therapy of > 12 months. Four patients (6%) discontinued therapy because of adverse events. Poor KPS (< 80%) and MSKCC poor-risk classification were prognostic for poor OS with hazard ratios of 4.09 (P < .001) and 2.84 (P = .021), respectively. ConclusionBevacizumab monotherapy resulted in prolonged disease control and few discontinuations because of adverse events in patients whose disease had progressed during treatment with other targeted therapies, including patients who were heavily pretreated.

Predictors of pathological upgrading and upstaging in patients eligible for active surveillance submitted to radical prostatectomy (RARP).

59 Background: To evaluate the pathological outcomes in patients who were suitable for Active Surveilance (AS) and underwent Radical Prostatectomy (RP) and to explore the potential predictive factors to identify Gleason upgrading and upstaging. Methods: A prospectively maintained database was used to evaluate 1,552 consecutive patients who underwent RP [Laparoscopic / Robotic] at our institution between 1998 and 2012. We identified 405 RP patients fulfilling the Memorial Sloan-Kettering Cancer Center criteria for AS (PSA ≤10 ng/ml, clinical stage ≤2a, Gleason≤6, ≤2 + cores and less 50% cancer in any one core). In the final RP specimen, upgrading was defined as identification of Gleason &gt;6 and upstaging as presence of ≥ pT3. The clinical and the pathological features of upstaged/upgraded patients were compared with the remaining patients and the cox’s regression model was applied to identify potential predictors. Kaplan Meir curve was used to identify Biochemical Recurrence Free Survival (BCR-FS) at 5 years. Results: We noticed upstaging in 195 (48%) patients and Gleason upgrading in 55 (13%) at RP specimen. Multivariate analysis showed percent of positive core had significant association with upstaging/upgrading. Positive Surgical Margin (PSM) was noted in 66(16%) patients, and the PSM rate was significantly higher in upstaged patients. The mean follow-up of the study population was 28 months and the predicted BCR-FS at 5 years was 92% and 88% in the patients who were not and were upstaged/upgraded. Conclusions: Percentage of positive cores in patients subjected to Active Surveillance appears to predict pathological upstaging/upgrading at radical prostatectomy. [Table: see text]

Impact of Race on Selecting Appropriate Patients for Active Surveillance With Seemingly Low-risk Prostate Cancer

To evaluate active surveillance (AS) criteria on their ability to predict favorable pathology at prostatectomy within a low-risk African American (AA) cohort. The sensitivity, specificity, positive predictive value, receiver operator curve, and area under the curve (AUC) were compared for 6 published AS criteria (National Comprehensive Cancer Network; Memorial Sloan-Kettering Cancer Center; Prostate Cancer Research International: Active Surveillance Study; Johns Hopkins-Epstein; University of California at San Francisco; and University of Miami) to predict organ-confined Gleason score 6 disease at prostatectomy in AAs and white Americans (WAs) with low-risk cancer. We also compared clinical parameters for AAs with favorable prostatectomy pathology with those for AAs with unfavorable pathology, and then used preoperative variables associated with unfavorable pathology as an additional exclusion criteria for AS. Of 468 patients with low-risk disease, 308 of 402 (76.6%) WAs and 55 of 66 (83.3%) AAs were eligible for AS by one or more criteria (P = .23). For WAs, Prostate Cancer Research International: Active Surveillance Study criteria had the highest rate of favorable pathology (81.7%) and the best performance (AUC = 0.70) in determining appropriate candidates for AS. However, all 6 AS criteria performed poorly for AA patients, with all AUCs ≤0.52. When comparing AAs with favorable pathology with AAs with unfavorable pathology, only family history of prostate cancer was statistically significant (11 of 25 [47.8%] vs. 8 of 41 [22.2%]; P = .04). When adjusting AS criteria in AAs to exclude those with a positive family history, the AUC increased most for the University of California at San Francisco (from 0.52 to 0.6) and Memorial Sloan-Kettering Cancer Center criteria (from 0.50 to 0.58). Current criteria underperform in appropriately selecting AAs for AS. AAs considering AS should be counseled about their increased risk for occult adverse pathology, particularly if a family history of prostate cancer is present.

Axitinib for preoperative downstaging of renal cell carcinoma with sarcomatoid differentiation and direct invasion of the duodenum and inferior vena cava: a case report

BackgroundRenal cell carcinoma (RCC) with sarcomatoid differentiation is invasive, refractory to treatment, and has a higher mortality. Therefore, systemic therapy is still challenging, and the curative resection of localized or locally advanced RCC with sarcomatoid differentiation is very important. Axitinib is a potent and selective second-generation vascular endothelial growth factor receptor tyrosine kinase inhibitor with improved safety and tolerability. Axitinib is generally recommended as second-line therapy for advanced RCC because the phase III axitinib versus sorafenib in advanced RCC (AXIS) trial demonstrated that it achieved longer progression-free survival than sorafenib in patients with metastatic RCC after failure of an approved first-line regimen.MethodsWe present a 73-year-old man who had a large (13 cm in diameter) right RCC with sarcomatoid differentiation that directly invaded the duodenum and inferior vena cava. The patient presented with gastrointestinal bleeding, was unable to eat solid food, and had become emaciated. Thus, his classification was poor risk with anemia, hypercalcemia, and poor performance status, according to the Memorial Sloan-Kettering Cancer Center criteria. He seemed unlikely to survive if radical nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed. To reduce the tumor burden and potential operative complications, we administered axitinib as first-line neoadjuvant therapy.ResultsSix weeks of treatment reduced the tumor burden without causing severe toxicities. Subsequently, radical right nephrectomy, cavotomy with thrombectomy, and pancreatoduodenectomy were performed successfully. The pathological treatment effect of axitinib was grade 2 (two-thirds necrosis). The resected tumor showed a heterogeneous reaction for phosphorylated Akt (Ser-473) by Western blotting and immunohistochemistry, indicating that parts of the tumor were sensitive to axitinib and other parts were not.ConclusionAxitinib might be promising as preoperative or neoadjuvant therapy for locally advanced RCC (>cT3b or >cTanyN1).

Validation of the MSKCC and Heng Risk Criteria Models for Predicting Survival in Patients with Metastatic Renal Cell Carcinoma Treated with Sunitinib

To validate the Memorial Sloan-Kettering Cancer Center (MSKCC) and Heng models with metastatic renal cell carcinoma treated with sunitinib, and to investigate prognostic factors in these patients. This study included 106 patients with metastatic renal cell carcinoma who were treated with sunitinib from April 2007 to July 2012 including 35 patients who received systemic treatment before sunitinib and 71 that were naive to systemic treatment. Patients were evaluated using the MSKCC and Heng models, and the significance of several prognostic factors were evaluated. The application of the MSKCC and Heng risk criteria resulted in stratification into 3 groups (favorable, intermediate, and poor risk) with distinctly different overall survival (OS) curves (P < 0.001 and P < 0.001, respectively), for the pretreated patients (P < 0.001 and P < 0.001, respectively). The Heng model had slightly better discriminatory ability (χ (2) = 30.82, Harrell's C = 0.6895) than the MSKCC model (χ (2) = 25.13, Harrell's C = 0.6532). Multivariate analysis revealed that the absence of nephrectomy and no hypertension at baseline, along with elevated C-reactive protein levels, were independent risk factors for poorer OS. The MSKCC and Heng model were both valid models for predicting OS. The no nephrectomy, no hypertension at baseline, and high C-reactive protein levels were independently associated with poorer OS.

A Phase II Study of Bevacizumab and Everolimus as Treatment for Refractory Metastatic Renal Cell Carcinoma

BackgroundAgents that inhibit the vascular endothelial growth factor (VEGF) and mammalian target of rapamycin (mTOR) pathways in metastatic renal cell carcinoma (mRCC) prolong progression-free survival (PFS), but durable complete responses are rare. Combinations of these cytostatic therapies have great potential to improve efficacy and to escape tumoral resistance mechanisms, but supra-additive toxicity is a valid concern. We investigated whether horizontal blockade with the combination of bevacizumab, a monoclonal antibody to VEGF-A, and of everolimus, an oral mTOR inhibitor, improved PFS in patients with clear cell mRCC who had received prior VEGF blockade. MethodsIn this phase II investigator-initiated study, 10 of 30 planned patients were enrolled. Bevacizumab 10 mg/kg was administered intravenously every 14 days. Everolimus was orally dosed at 10 mg daily. The patients were treated until disease progression or unacceptable toxicity. The primary endpoint was PFS. ResultsThe median age was 55 years. The majority of patients were white men with an Eastern Cooperative Oncology Group performance status of 1 (80%) and intermediate risk disease by Memorial Sloan-Kettering Cancer Center criteria (70%). All the patients had received 1 prior VEGF inhibitor. The median PFS in the 10 evaluable patients was 5.1 months, which was less than the expected historical control of bevacizumab monotherapy at 6 months. The median overall survival was 21 months. The best response was a partial response in 1 patient and stable disease in 9. Forty percent of the patients were discontinued from the study due to toxicity. ConclusionsIn our experience, the combination of bevacizumab and everolimus was toxic. The efficacy achieved did not support its combined use over sequential administration. Ongoing randomized studies will definitively evaluate the combination's efficacy and tolerability.

P1-123 - Efficacy and Safety of Sunitinib in Patients with Non-Clear Cell Renal Cell Carcinoma

ABSTRACT Background Retrospective and molecular biological data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma (nccRCC). Methods Eligibility criteria included advanced nccRCC except for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes. Patients were treated with 50 mg/day oral sunitinib for 4 weeks, followed by 2 weeks of rest. The primary end point was the overall response rate. Results Thirty-one eligible patients were enrolled. Twenty-four patients (77%) had prior nephrectomy. By Memorial Sloan-Kettering Cancer Center criteria, 8 patients (26%) had poor risk and 14 (45%) had intermediate risk. Twenty-two patients had papillary RCC, and 3 had chromophobe RCC. Eleven patients had partial response, with a response rate of 36% (95% CI, 19–52%) and an additional 17 patients (55%) had stable disease. The median duration of response was 12.7 months (95% CI: 6.3–19.1 months), and the median progression-free survival was 6.4 months (95% CI: 4.2–8.6 months). At a median follow-up duration of 18.7 months (95% CI: 13.7–23.7 months), 13 patients (42%) had died, resulting in an estimated median survival of 25.6 months (95% CI: 8.4–42.9 months). Toxicity profiles were commensurate with prior reports. Conclusions Sunitinib has promising activity in patients with nccRCC. (NCT01219751) Final survival results will be reported in the meeting.

Possible improvement of survival with use of zoledronic acid in patients with bone metastases from renal cell carcinoma

Bisphosphonates play an indisputable role in preventing skeletal-related events (SREs) secondary to bone metastases, and also have a direct effect on tumor cells. However, it remains unclear whether bisphosphonates improve overall survival (OS) for renal cell carcinoma (RCC) patients with bone metastases. Between 1978 and 2010, a total of 45 patients who had RCC metastatic to bone and were classified as intermediate risk according to Memorial Sloan-Kettering Cancer Center criteria were included in this retrospective study. In this cohort, 23 patients received zoledronic acid (ZOL) treatment (ZOL-treated group) whereas the other 22 did not (non-ZOL-treated group). The primary endpoint was OS and the secondary endpoint was the SRE rate defined as the total number of SREs divided by the total years under study. For the cohort of 45 patients, the median OS from diagnosis of bone metastases was 27.2 months. Multivariate analysis showed that lower serum calcium (p = 0.0083) and ZOL treatment (p = 0.0013) were independent factors predicting longer survival. The ZOL-treated group had significantly longer OS than the non-ZOL-treated group (p = 0.0034). Patients in the ZOL-treated group experienced a lower SRE rate than patients in the non-ZOL-treated group (p = 0.0453). In particular, none of the patients in the ZOL-treated group developed spinal compression whereas 6 (28%) in the non-ZOL-treated group did (p = 0.0479). The current study indicates that ZOL not only reduces SREs but possibly improves OS in these patients.

Multicenter phase II study of sunitinib in patients with non-clear cell renal cell carcinoma

Retrospective and molecular biologic data suggest that sunitinib may be effective in patients with non-clear cell renal cell carcinoma (nccRCC). Eligibility criteria included advanced nccRCC except for collecting duct carcinoma and sarcomatoid carcinoma without identifiable renal cell carcinoma subtypes. Patients were treated with 50 mg/day oral sunitinib for 4 weeks, followed by 2 weeks of rest. The primary end point was overall response rate (RR). Thirty-one eligible patients were enrolled. Twenty-four patients (77%) had prior nephrectomy. By Memorial Sloan-Kettering Cancer Center criteria, 8 patients (26%) had poor risk and 14 (45%) had intermediate risk. Twenty-two patients had papillary renal cell carcinoma (RCC), and three had chromophobe RCC. Eleven patients had partial response with a RR of 36% (95% confidence interval (CI) 19% to 52%) and an additional 17 patients (55%) had stable disease. Median duration of response was 12.7 months (95% CI 6.3-19.1 months), and median progression-free survival was 6.4 months (95% CI 4.2-8.6 months). At a median follow-up duration of 18.7 months (95% CI 13.7-23.7 months), 13 patients (42%) had died, resulting in an estimated median survival of 25.6 months (95% CI 8.4-42.9 months). Toxicity profiles were commensurate with prior reports. Sunitinib has promising activity in patients with nccRCC (NCT01219751).

Clinical outcome in patients receiving systemic therapy for metastatic sarcomatoid renal cell carcinoma: A retrospective analysis☆

ObjectivesSarcomatoid metastatic renal cell carcinoma (mRCC) represents an aggressive subset of disease, and a definitive therapeutic strategy is lacking. We seek to define outcomes associated with systemic therapy (including immunotherapy, cytotoxic therapy, and targeted agents) for sarcomatoid mRCC, with attention to novel prognostic schema. Materials and methodsFrom an institutional database including 270 patients with mRCC, we identified 34 patients with documented sarcomatoid features. Within this cohort, we assessed 21 patients who received systemic therapy. Survival was assessed in the overall cohort and in subgroups divided by clinicopathologic characteristics, including the extent of sarcomatoid features, Memorial Sloan-Kettering Cancer Center (MSKCC) risk criteria, Heng criteria, and the nature of systemic therapy rendered. ResultsOf the 21 patients assessed, 2 patients received chemotherapy, 7 patients received immunotherapy, and 12 patients received targeted agents as their first line treatment. Median overall survival (OS) in the overall cohort was 18.0 months (95% CI 6.9–22.0). By MSKCC criteria, patients with poor-risk disease had a median OS of 4.7 months, compared with 20.1 months for patients with intermediate-risk disease [hazard ratio (HR) 0.02, 95%CI 0.003–0.15; P = 0.0001]. A similar difference in median OS was seen poor- and intermediate-risk groups when stratifying by Heng criteria (HR 0.17, 95%CI 0.001–0.12). There was no significant difference in survival in patients with sarcomatoid predominant disease vs. nonpredominant disease (HR 0.62, 95%CI 0.23–1.65; P = 0.34), nor was there a difference amongst patients who received targeted therapies vs. nontargeted therapies (HR 1.0, 95%CI 0.61–1.40; P = 0.36). ConclusionsCompared with previous series and prospective trials assessing patients with sarcomatoid mRCC, the observed survival was prolonged. Although both Heng and MSKCC risk scores may be useful in determining prognosis, further studies are needed to identify relevant biomarkers and define the optimal therapeutic strategy for this disease.

Validation of MSKCC-criteria in metastatic renal cancer patients treated with sorafenib or sunitinib.

401 Background: To validate the Memorial Sloan-Kettering Cancer Center (MSKCC) criteria as a prognostic factor in patients with metastatic renal cell carcinoma (mRCC) treated with the tyrosine kinase inhibitors (TKIs) sorafenib (So) or sunitinib (Su). Methods: Clinical and laboratory parameters from 83 patients with mRCC were investigated. All patients were treated at our institution between 2006 and 2009. Specifically, the MSKCC criteria (Karnofsky performance status &lt;80%, time between diagnosis and treatment &lt; 1 year, baseline anemia, elevated LDH &gt; 1.5 times upper limit of normal, and elevated serum calcium) were evaluated as surrogate parameters for progression-free survival (PFS). Results: 34 (41.0%) patients were treated as first-line, and 49 (59.0%) patients were treated as second-line treatments, respectively. In univariate analyses, a poor ECOG status was associated with an unfavorable progression-free survival (p&lt;0.0001); similarly high risk MSKCC criteria correlated with a worse PFS (p=0.003). Furthermore, response to therapy was a surrogate parameter (p&lt;0.0001). Albeit statistically not significant, prior nephrectomy (p=0.056), histologic subtype (p=0.052) as well as baseline anemia (p=0.079) tended to be associated with PFS. In multivariate analyses, only the ECOG status (ECOG 0/1 vs. ECOG 2, p=0.001) and best treatment response (p&lt;0.001) were independent prognostic markers, but not MSKCC criteria. Conclusions: In this patient cohort, MSKCC criteria did not show prognostic relevance in terms of PFS. The role of risk group stratification according to MSKCC in patients with mRCC and treatment with TKIs must be questioned. No significant financial relationships to disclose.

Use of CXCR4 expression to predict the efficacy of sorafenib treatment in patients with metastatic renal cell carcinoma.

359 Background: CXCR4, a chemokine receptor, is implicated in the metastastic process. Higher expression of CXCR4 in renal cell carcinoma predicts shorter disease-free survival and poorer prognosis. This study aims to investigate the relationship of CXCR4 expression with the efficacy of target drugs in treatment of metastatic renal cell carcinoma (mRCC). Methods: A total of 58 patients with mRCC treated with target drugs (26 with sorafenib, 23 with sunitinib, 5 with pazopanib, 2 with CCI-779, and 2 with axitinib) as the first-line therapy in Beijing Cancer Hospital between 2006 and 2010 were investigated. CXCR4 expression in tissue was detected by immunohistochemistry. Survival curves were estimated according to the Kaplan-Meier method and evaluated with the Log-rank test. The correlation of CXCR4 expression with Memorial Sloan-Kettering Cancer Center criteria (MSKCC) was assessed with χ2 test. p &lt; 0.05 was considered statistically significant. Results: CXCR4 expression was negative in 6.9% (4/58) of patients, low in 19.0% (11/58) of patients, intermediate in 56.9% (33/58) of patients and high in 17.2% (10/58) of patients, which was not correlated with MSKCC (p = 0.143). The PFS of patients with negative or low CXCR4 expression (20.0 ± 5.9 months) was longer than those with intermediate or high expression (8.5 ± 1.3 months), which, however, was not statistically different (p = 0.131). The PFS of sorafenib-treated patients with negative or low CXCR4 expression was 20.0±8.0 months while the patients with intermediate or high CXCR4 expression was 6.0 ± 0.8 months (p = 0.038). No such correlation existed in the group of patients treated with sunitinib (p = 0.947). And median OS had not been achieved yet. Conclusions: CXCR4 can predict the efficacy of sorafenib treatment in mRCC patients. Patients with negtive or low CXCR4 expression are more likely to obtain longer PFS than those with intermediate or high CXCR4 expression. [Table: see text]

Phase II Presurgical Feasibility Study of Bevacizumab in Untreated Patients With Metastatic Renal Cell Carcinoma

To assess safety and efficacy of presurgical bevacizumab in patients with metastatic renal cell carcinoma (mRCC), and to explore the hypothesis that pretreatment of patients with antiangiogenic therapy will select patients who benefit most from cytoreductive nephrectomy. Patients with newly diagnosed, clear cell mRCC whose primary tumors were considered resectable were enrolled. In this single-arm, phase II trial, patients received bevacizumab plus erlotinib (first patients, n = 23) or bevacizumab alone (n = 27 patients) for 8 weeks followed by restaging. If patients demonstrated progressive disease and had declining performance statuses after 8 weeks, nephrectomy procedures were deferred. Postoperatively, patients continued on the study drug or drugs if disease stabilization or regression had occurred. Between March 2005 and March 2008, 52 patients were enrolled on study, and 50 were included in the analysis. By Memorial Sloan-Kettering Cancer Center criteria, 82% of patients had intermediate-risk, and 18% had poor-risk, features. Forty-two patients underwent nephrectomy. Median progression-free survival was 11.0 months (95% CI, 5.5 to 15.6 months). Median overall survival was 25.4 months (95% CI, 11.4 months to not estimable). Two perioperative deaths occurred; neither was attributable to study drug. Wound dehiscence resulted in treatment discontinuation for three patients and treatment delay for two others. Presurgical treatment with bevacizumab therapy yields clinical outcomes comparable to post-surgical treatment with antiangiogenic therapy in patients with mRCC, but it may result in wound-healing delays. Prospective, randomized trials to test the use of presurgical therapy as a method to select appropriate patients for cytoreductive nephrectomy are warranted.