Monosomy of Chromosome 9 Is Associated With Higher Grade,Advanced Stage,and Adverse Outcome in Clear-cell Renal Cell Carcinoma

BackgroundClear-cell renal cell carcinoma (ccRCC) is one of the most common malignancies in humans and is usually associated with poor outcomes. Cancers are considered to be genetic diseases. Therefore, a better understanding of genetic alterations that are related to disease progression or poor prognosis can help to more precisely identify high-risk patients and treat them more effectively. The aim of this study was to examine the frequency of whole chromosome 9 loss (monosomy of chromosome 9) and its prognostic value in patients with ccRCC.Materials and MethodsSingle nucleotide polymorphism-based chromosome microarray (CMA) analysis was performed on 103 resected specimens from patients with ccRCC who had undergone partial or radical nephrectomy between January 2002 and March 2017 at Fox Chase Cancer Center. Monosomy 9 was correlated with clinicopathologic parameters and recurrence-free survival.ResultsChromosome 9 loss was detected in 31 (30%) of 103 tumors. Tumors with chromosome 9 loss had higher histologic grade (3 and 4; P < .001) and pathologic stage (P < .001). In 59 patients with non-metastatic ccRCC, chromosome 9 loss was also associated with higher recurrence rate and shorter recurrence-free survival (RFS) (12-month RFS, 77.8%; 95% confidence interval, 36.5%-93.9% for chromosome 9 loss vs. 95.7%; 95% confidence interval, 84.0%-98.9% for no loss; P = .002).ConclusionsChromosome 9 loss was found in 30% of patients with ccRCC and correlated with higher grade, advanced stage, and shorter RFS in patients with Stage I to III ccRCC.     

The Impact of Age and Gender on Outcomes of Patients With Advanced Renal Cell Carcinoma Treated With Targeted Therapy

BackgroundA growing body of evidence suggests that age and gender play a role in cancer outcomes. The objective of this study was to investigate the effect of age and gender on survival of patients with metastatic renal cell carcinoma (RCC).MethodsWe conducted a pooled analysis of patients with metastatic RCC treated on phase II and III clinical trials. Patients were stratified by age (young [<50 years], intermediate [50-70 years], versus elderly [>70 years]) and gender. Statistical analyses were performed using Cox regression adjusted for several risk factors and the Kaplan-Meier method.ResultsWe identified 4736 patients with metastatic RCC. Overall, there was no difference in overall survival (OS) when stratified by age (21.0 vs. 17.3 months for elderly vs. intermediate age groups, P = .382; 20.0 vs. 17.3 months for young vs. intermediate age groups, P = .155) or gender (19.8 vs. 19.0 for male vs. female, P = .510). Progression-free survival (PFS) was shorter in younger individuals compared with the intermediate age patients (6.0 vs. 7.1 months, P < .001), but similar across gender groups. Although all grade adverse events were more common in elderly patients (fatigue, diarrhea, decreased appetite, and weight), serious adverse events were similar between groups.ConclusionsAlthough OS was similar between age groups, younger individuals had a shorter PFS. Gender was not an independent determinant of survival. Elderly patients experienced more adverse events than their younger counterparts. These findings are important to guide clinicians when counseling patients about expectations and toxicity associated with therapy.     

Real-world Experience With Sunitinib Treatment in Patients With Metastatic Renal Cell Carcinoma: Clinical Outcome According to Risk Score

BackgroundADONIS is an ongoing observational study in 9 European countries, designed to evaluate treatment patterns/outcomes in patients with metastatic renal cell carcinoma (mRCC) treated with first-line sunitinib and/or second-line axitinib post sunitinib. We present an evaluation of sunitinib efficacy by risk group, in the real-world setting examined in ADONIS.Patients and MethodsPatients were enrolled at the start of first-line sunitinib treatment or second-line axitinib post sunitinib treatment. Evaluation of sunitinib efficacy was assessed by International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and Memorial Sloan Kettering Cancer Center risk criteria.ResultsFor all patients in this analysis (N = 467), the median progression-free survival was 23.8 months (95% confidence interval [CI], 16.5-28.5 months), 11.8 months (95% CI, 8.1-17.4 months), and 4.6 months (95% CI, 2.5-7.7 months) for IMDC favorable-, intermediate-, and poor-risk groups, respectively. The median overall survival was 97.1 months (95% CI, 46.3 months-not evaluable [NE]), 33.5 months (95% CI, 20.5-46.6 months), and 10.0 months (95% CI, 4.5-19.8 months) for the respective risk groups. Data on individual risk factors were available for a subgroup of patients, allowing analysis by intermediate risk by 1 versus 2 risk factors. When including this subgroup (n = 120), the median overall survival for IMDC favorable-, intermediate-1, and intermediate-2 risk factors was 21.6 months (95% CI, 16.3 months-NE), 20.5 months (15.5 months-NE), and 15.1 months (4.1 months-NE), respectively.ConclusionsFor patients overall and by risk-group stratification, survival estimates were aligned with previously published data. In patients with intermediate-1 risk, overall survival was very similar to patients with favorable risk. However, further exploration of outcome data from different sources is needed to confirm these observations.     

Oncologic Outcomes of Partial Nephrectomy for Stage T3a Renal Cell Cancer

Background

Partial nephrectomy (PN) for clinical stage T3 tumors is controversial. Radical nephrectomy (RN) has been associated with a greater rate of chronic kidney disease, an increased risk of cardiovascular disease, and increased mortality compared with PN. We present our long-term 2-center experience with PN for stage pT3a tumors and compare the oncologic outcomes with those of similar patients treated with RN.

Female Gender Predicts Favorable Prognosis in Patients With Non-metastatic Clear Cell Renal Cell Carcinoma Undergoing Curative Surgery: Results From the International Marker Consortium for Renal Cancer (INMARC)

BackgroundThere is no clear consensus regarding gender differences in the prognosis of patients with clear-cell renal cell carcinoma (ccRCC). In the present study, we investigated the prognostic value of gender in patients with non-metastatic ccRCC undergoing curative surgery using the inverse probability of treatment weighting (IPTW) method to balance the difference in baseline factors between females and males.Patients and MethodsWe retrospectively reviewed the International Marker Consortium for Renal Cancer (INMARC) dataset and included 2055 patients with cT1-4N0M0 ccRCC who underwent partial or radical nephrectomy. The IPTW method was used to adjust for baseline characteristics between females and males (age, race, surgery type, and pT stage), and the association of gender with recurrence-free survival (RFS) was evaluated.ResultsDuring the follow-up (median, 30 months), 162 (8%) patients had disease recurrence (5-year RFS rate, 88%). Female gender (n = 712; 35%) was significantly associated with a lower Fuhrman grade (unweighted, P = .022; IPTW-weighted, P < .001). Females had significantly better RFS compared with males (unweighted, 5-year RFS rate, 92% vs. 87%; P = .005; IPTW-weighted, 5-year RFS rate, 92% vs. 86%; P = .002). IPTW-weighted multivariate analysis showed that female gender was an independent predictor for better RFS (hazard ratio, 0.59; P = .005) along with lower pT stage and lower Fuhrman grade. The prognostic significance of female gender was also observed in the unweighted multivariate analysis.ConclusionFemale gender was significantly associated with a lower Fuhrman grade and better prognosis for patients with non-metastatic ccRCC undergoing curative surgery.     

The Relationship Between Red Cell Distribution Width and Cancer-Specific Survival in Patients With Renal Cell Carcinoma Treated With Partial and Radical Nephrectomy

Introduction

The aim of the study was to evaluate the influence of red cell distribution width (RDW) on cancer-specific survival (CSS) in patients who undergo nephrectomy for renal cell carcinoma (RCC).

Capturing Renal Cell Carcinoma Recurrences When Asymptomatic Improves Patient Survival

Introduction

The purpose of this study was to explore whether the practice of postoperative renal cell carcinoma (RCC) surveillance affords a survival benefit by investigating whether detection of RCC recurrences in an asymptomatic versus symptomatic manner influences mortality.

Prognostic Factors in Patients With Advanced Renal Cell Carcinoma

BackgroundThe purpose of this study was to evaluate prognostic factors in patients with RCC.Materials and MethodsThe expression of several biomarkers were measured by immunohistochemistry (IHC), together with 2 analytic factors (thrombocytosis and neutrophilia), in 135 patients with advanced RCC treated with new targeted drugs (NTDs) (n = 67) and/or cytokines (CKs) (n = 68)—with 23 of the patients who received CKs also receiving NTDs—between July 1996 and February 2010. Relationships with overall survival (OS) and progression-free survival (PFS) were searched for.ResultsUnivariate statistical analysis revealed that high expression of hypoxia-inducible factor-1α (HIF-1α) correlated with poor prognosis in NTD treatment (PFS, 5.4 vs. 13.5, low expression months; P = .033) and CK treatment (PFS, 3.3 vs. 5.7, low expression; P = .003). Overexpression of carbonic anhydrase IX (CAIX) was associated with better prognosis with NTD treatment (OS, 32.1 vs. 7.8 months; P < .001) and CK treatment (OS, 32.9 vs. 5.9 months; P = .001). Positive PTEN was related to good prognosis with sunitinib (PFS, 15.1 vs. 6.5 months; P = .003) and CKs (OS, 13.7 vs. 7.9 months; P = .039). Increased expression of p21 was related to poor prognosis with NTD treatment (PFS, 5.9 vs. 16.8 months; P = .024) and CK treatment (PFS, 3.9 vs. 7.5 months; P < .001) Thrombocytosis was related to poor prognosis with NTDs (OS, 15.9 vs. 26.7 months; P = .007) and CKs (OS, 5.9 vs. 14.3 months; P = .010). Neutrophilia was related to poor prognosis with NTDs (OS, 17.6 vs. 25.4 months; P = .063) and CKs (OS, 5.9 vs. 12.8 months; P = .035). Multivariate analysis revealed that overexpression of CAIX was a favorable prognostic factor independent of PFS (hazard ratio [HR], 0.107; P < .001) and OS (HR, 0.055; P < .001).ConclusionsHIF-1α, PTEN, p21, thrombocytosis, neutrophilia, and CAIX in particular are useful prognostic factors in patients with advanced RCC.     

Exploratory Investigation of Target Pazopanib Concentration Range for Patients With Renal Cell Carcinoma

BackgroundSevere adverse events frequently occur in patients treated with pazopanib, necessitating dose reduction and discontinuation. However, information on the exposure-toxicity relationship is limited.Patients and MethodsFor this retrospective and observational clinical study, we examined 27 patients with renal cell carcinoma treated with pazopanib and enrolled between October 2014 and March 2018. The primary goal was to evaluate the association between trough pazopanib concentration and occurrence of grade ≥ 3 toxicities, and secondarily, to estimate the association between trough pazopanib concentration and objective response rate.ResultsMean trough pazopanib concentration was significantly higher in the grade ≥ 3 toxicity group (n = 9) than in the grade ≤ 2 toxicity group (n = 18). Based on the receiver operating characteristic curve, the threshold value of trough pazopanib concentration for predicting grade ≥ 3 toxicities was 50.3 μg/mL (area under the curve, 0.85; 95% confidence interval, 0.70-0.99; P < .05). In the pazopanib < 20.5 μg/mL group (n = 3), no patient experienced an objective response. Objective response rates between patients with 20.5 to 50.3 μg/mL pazopanib (n = 11) and patients with ≥ 50.3 μg/mL (n = 13) were similar (45.5% vs. 46.2%).ConclusionFrom results of this study, the target trough pazopanib concentration range may be 20.5 to 50.3 μg/mL for patients with renal cell carcinoma.     

Effect of Comorbidities in Stage II/III Colorectal Cancer Patients Treated With Surgery and Neoadjuvant/Adjuvant Chemotherapy: A Single-Center,Observational Study

Background

Comorbidity has a detrimental effect on cancer survival, however, it is difficult to disentangle its direct effect from its influence on treatment choice. In this study we assessed the effect of comorbidity on survival in patients who received standard treatment for resected stage II and III colorectal cancer (CRC).

Molecular Subtypes of Clear Cell Renal Cell Carcinoma Are Associated With Outcome During Pazopanib Therapy in the Metastatic Setting

Background

We previously described 4 molecular subtypes of metastatic clear cell renal cell carcinoma (mccRCC), named ccrcc1-4 (Beuselinck et al, 2015). These have both prognostic and predictive value for patients treated with first-line sunitinib, with distinctive objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). The ccrcc2 and ccrcc3 tumors have the best outcomes, followed by ccrcc1 and then ccrcc4. We hypothesized that these molecular subtypes would show similar outcomes with first-line pazopanib treatment.

Effect of Surgery at Primary and Metastatic Sites in Patients With Stage IV Breast Cancer

BackgroundThere is no clear evidence of a survival benefit of resection of the primary tumor, or distant site resection (metastasectomy) in patients with stage IV breast cancer.Patients and MethodsThis retrospective analysis of stage IV breast cancer using the National Cancer Database. To evaluate variables associated with surgery at the primary site, we used univariate analyses followed by multivariate logistic regression. Consequently, we evaluated the impact of lumpectomy, mastectomy or metastasectomy on survival by conducting multivariate Cox regression survival analyses on the following groups: all stage IV patients; a subset of those with only one metastatic site; and another subset with metastasis to multiple distant sites.ResultsA total of 54,871 stage IV breast cancer patients were included in this analysis. Variables associated with the use of surgery at the primary were: age, race, Charlson/Deyo score, insurance and facility type, involved breast quadrant, receptor status, N stage, extent of metastasis, and year of diagnosis. Survival analysis showed that both lumpectomy (median overall survival [OS], 45 months) and mastectomy (median OS, 44 months) were associated with better OS compared to no surgery (median OS, 22 months). The statistical effect was larger in the subgroup with metastasis to one site, but still significant in the subgroup with multiple metastatic sites. Distant site resection also yielded a survival benefit.ConclusionIn patients with metastasis to only one site, metastasectomy was associated with better OS when that site was the liver, lung, or brain.     

Sunitinib in Patients With Metastatic Renal Cell Carcinoma: Clinical Outcome According to International Metastatic Renal Cell Carcinoma Database Consortium Risk Group

Background

Sunitinib malate, a targeted tyrosine kinase inhibitor, is standard of care for metastatic renal cell carcinoma (mRCC) and serves as the active comparator in several ongoing mRCC clinical trials. In this analysis we report benchmarks for clinical outcomes on the basis of International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk groups for patients treated with sunitinib for mRCC in a first-line setting.

Clinical Factors Associated With Long-Term Benefit in Patients With Metastatic Renal Cell Carcinoma Treated With Axitinib: Real-World AXILONG Study

BackgroundAxitinib monotherapy obtained approval in pre-treated mRCC patients and recently in combination with pembrolizumab or avelumab in the first-line setting. However, patient profiles that may obtain increased benefit from this drug and its combinations still need to be identified.Patients and MethodsRetrospective multicentre analysis describing clinical characteristics associated with axitinib long-responder (LR) population by comparing two extreme-response sub-groups (progression-free survival [PFS] ≥9 months vs. disease progression/refractory patients [RP]). A multivariate logistic-regression model was used to analyse clinical factors. Efficacy and safety were also analysed.ResultsIn total, 157 patients who received axitinib in second or subsequent line were evaluated (91 LR and 66 RP). Older age at start of axitinib and haemoglobin levels > LLN were independent predictive factors for LR in multivariate analyses. In LR patients, median (m) PFS was 18.1 months, median overall survival was 36.0 months and objective response rate (ORR) was 45.5%. In 59 LR patients receiving axitinib in second-line, mPFS was 18.7 months, mOS was 44.8 months and ORR was 43.9%. mOS was significantly longer in second line compared to subsequent lines (44.8 vs. 26.5 months; P = .009). In LR vs. RP, mPFS with sunitinib in first-line was correlated with mPFS with axitinib in second-line (27.2 vs. 10.9 months P < .001). The safety profile was manageable and consistent with known data.ConclusionsThis study confirms the long-term benefits of axitinib in a selected population, helping clinicians to select the best sequential approach and patients who could obtain a greater benefit from axitinib.     

Dosing Patterns,Toxicity, and Outcomes in Patients Treated With First-Line Sunitinib for Advanced Renal Cell Carcinoma in Community-Based Practices

BackgroundThis retrospective study by McKesson Specialty Health (MSH)/US Oncology Network (USON) evaluates dosing patterns of first-line sunitinib for patients with advanced renal cell carcinoma (aRCC) and its association with toxicities and clinical outcomes in community practices.Patients and MethodsPatients with aRCC who started first-line sunitinib between June 1, 2007, and May 31, 2011, were identified from 17 MSH/USON practices. Clinical data were extracted from iKnowMed electronic medical records linked to the MSH/USON pharmacy database.ResultsIn total, 134 patients were included; mean age was 63.9 years, 85% of the patients had an Eastern Cooperative Oncology Group performance score of 0 or 1, 82% had clear-cell renal cell carcinoma, and 65% had undergone nephrectomy. The median treatment duration was 4 cycles (range, 1-19). Overall, 113 patients discontinued sunitinib, mainly because of disease progression (45.1%) or toxicities (16.8%). Of all discontinuations, 77% occurred within the first 5 cycles. A total of 45 patients were dose-reduced, mostly because of toxicities (93%); 67% of all dose reductions occurred in the first 3 cycles. The objective response rate was 16.4%, median overall survival (OS) was 15.5 months, and progression-free survival (PFS) was 7.5 months. Multivariate analysis showed that OS and PFS were associated with sunitinib treatment duration.ConclusionsPatients with aRCC from community practices undergo sunitinib dose reductions more frequently because of toxicities and discontinue therapy sooner than in clinical trials. Clinical outcomes were inferior to those reported in clinical trials, potentially because of shorter duration of therapy. Sunitinib therapy optimization remains an important challenge in community practices.     

Predictive Factors for Late Recurrence in Patients With Stage T1 Clear Cell Renal Cell Carcinoma: A Multiinstitutional Study

BackgroundThe purpose of this study was to identify predictive factors for late recurrence in Korean patients with stage T1 clear cell renal cell carcinoma (RCC) more than 5 years after treatment with radical nephrectomy (RN) or partial nephrectomy (PN).Patients and MethodsBetween 1999 and 2011, 3567 patients with RCC underwent RN or PN at 5 institutions in Korea. Of these, 423 patients with pathologically confirmed stage T1 clear cell RCC remained free of disease for at least 5 years. To determine the pathologic and clinical factors that influenced late recurrence, univariate and multivariate analyses using the Cox proportional hazards model were performed. Recurrence-free survival curves were estimated by using the Kaplan-Meier method.ResultsDuring a median follow-up period of 83.9 months (range 60.0-156.4 months), late recurrence was observed in 14 of the 423 (3.3%) patients. Univariate and multivariate analyses revealed that symptoms at diagnosis and pathologic T stage were independent predictive factors for late recurrence. Patients with symptoms at diagnosis or stage T1b disease had a significantly shorter time to late recurrence than did those who were asymptomatic or had stage T1a disease (log-rank test P = .027 and P = .034, respectively).ConclusionsLate recurrence in stage T1 clear cell RCC is a relatively rare event. Predictive factors for late recurrence were identified in the present study. Careful long-term follow-up is necessary, especially in patients who have symptoms at diagnosis or stage T1b tumors, even if they have been free of disease for more than 5 years.