Pre-treatment neutrophil/lymphocyte ratio and platelet/lymphocyte ratio are prognostic of progression in early stage classical Hodgkin lymphoma.

To determine whether pre-treatment neutrophil/lymphocyte (NLR) or platelet/lymphocyte ratios (PLR) are predictive for progression in early-stage classical Hodgkin lymphoma (cHL), we derived NLR and PLR values for 338 stage I/II cHL patients and appropriate cut-off point values to define progression. Two-year freedom from progression (FFP) for patients with NLR ≥6·4 was 82·2% vs. 95·7% with NLR <6·4 (P < 0·001). Similarly, 2-year FFP was 84·3% for patients with PLR ≥266·2 vs. 96·1% with PLR <266·2 (P = 0·003). On univariate analysis, both NLR and PLR were significantly associated with worse FFP (P = 0·001). On multivariate analysis, PLR remained a significant, independent prognostic factor (P < 0·001).

Outcomes of unselected patients with metastatic clear-cell renal cell carcinoma treated with first-line pazopanib therapy followed by vascular endothelial growth factor receptor tyrosine kinase inhibitors or mammalian target of rapamycin inhibitors: a single institution experience.

OBJECTIVE: To explore the efficacy and safety of pazopanib in a 'real-world' setting in unselected patients, as data regarding unselected patients with metastatic clear-cell renal cell carcinoma (ccRCC) treated with first-line pazopanib are limited. PATIENTS AND METHODS: We reviewed records of patients with metastatic ccRCC treated with first-line pazopanib from 1 November 2009 through to 1 November 2012. Cox models were fitted to evaluate the association of progression-free survival (PFS) and overall survival (OS) with patient co-variables. RESULTS: In all, 88 patients were identified; 74 were evaluable for response: two (3%) had a complete response, 27 (36%) a partial response, 36 (49%) had stable disease and nine (12%) had progressive disease. The median PFS was 13.7 months [95% confidence interval (CI) 8.7-18.3]. PFS was correlated with a Karnofsky Performance Status score of <80 [hazard ratio (HR) 3.26, P < 0.001] and serum lactate dehydrogenase of >1.5 × upper limit of normal (HR 3.25, P = 0.014). The median OS was 29.1 months (95% CI 20.2-not reached). The OS was correlated with brain metastasis (HR 2.55, P = 0.009), neutrophilia (HR 1.179, P = 0.018), and anaemia (HR 3.51, P < 0.001). There were no treatment-related deaths. In all, 53 patients received second-line therapy [vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKI) in 22 patients, mammalian target of rapamycin inhibitors (mTORi) in 22 patients, and other therapy in nine patients]; the median PFS was 8.6 months (95% CI 3.3-25.7) with VEGFR-TKI and 5 months (95% CI 3.5-15.2) with mTORi (P = 0.41); the median OS was 19.9 months (95% CI 12.9-not reached) and 14.2 months (95% CI 8.1-not reached), from initiation of second-line VEGFR-TKI or mTORi, respectively (P = 0.37). CONCLUSIONS: In this retrospective study, first-line pazopanib confirmed its efficacy in metastatic ccRCC. Trends for longer PFS and OS were seen with VEGFR-TKI compared with mTORi after first-line pazopanib.

Prognosis of patients with metastatic renal cell carcinoma and pancreatic metastases.

OBJECTIVES: To identify the clinical outcomes of patients with metastatic renal cell carcinoma (mRCC) with pancreatic metastases (PM) treated with either pazopanib or sunitinib and assess whether PM is an independent prognostic variable in the current therapeutic environment. PATIENTS AND METHODS: A retrospective review of patients with mRCC in an outpatient clinic was carried out for the period January 2006 to November 2011. Patient characteristics, including demographics, laboratory data and outcomes, were analysed. Baseline characteristics were compared using chi-squared and t-tests and overall survival (OS) and cancer-specific survival (CSS) rates were estimated using Kaplan-Meier methods. Predictors of OS were analysed using Cox regression. RESULTS: A total of 228 patients were reviewed, of whom 44 (19.3%) had PM and 184 (81.7%) had metastases to sites other than the pancreas. The distribution of baseline characteristics was equal in both groups, with the exception of a higher incidence of previous nephrectomy, diabetes and number of metastatic sites in the PM group. Four patients had isolated PM, but the majority of patients (68%) with PM had at least three different organ sites of metastases, as compared with 29% in patients without PM (P < 0.01). The distribution of organ sites of metastases was similar, excluding the pancreas, in those with and those without PM (P > 0.05). The median OS was 39 months (95% confidence interval [CI] 24-57, hazard ratio 0.66, 95% CI 0.42-0.94; P = 0.02) for patients with PM, compared with 26 months (95% CI 21-31) for patients without PM (P < 0.01). CSS was 42 months (95% CI 30-57) in the PM group and 27 months (95% CI 22-33) in the control group (P = 0.05). CONCLUSIONS: Despite a higher number of affected organ sites in the PM cohort, mRCC behaviour in this cohort appears to be more indolent, as demonstrated by a higher median OS. These findings suggest that host or tumour features associated with PM may represent a less aggressive tumour phenotype.

Proteinuria with first-line therapy of metastatic renal cell cancer.

BACKGROUND: Vascular endothelial growth factor receptor inhibitors, mammalian target of rapamycin inhibitors, and tyrosine kinase inhibitors are approved for metastatic renal cell cancer. Proteinuria can occur, but there is limited data regarding the incidence, monitoring, and management in metastatic renal cell cancer patients. OBJECTIVE: Our primary objective was to describe the incidence and severity of proteinuria in metastatic renal cell cancer patients treated in the first-line setting with pazopanib, bevacizumab, or everolimus. METHODS: We conducted a retrospective review of patients with metastatic renal cell cancer enrolled from January 2011-April 2013 in a phase II trial. Baseline and toxicity data were extracted from the electronic medical record. Descriptive statistics were used. RESULTS: In all, 129 patients were eligible for analysis. The overall incidence of proteinuria was 81%, with most events being Grade 1 or 2. The incidence of proteinuria was 80% (n = 35) for pazopanib, 64% (n = 25) for bevacizumab, and 96% (n = 44) for everolimus. At peak proteinuria, 80% (n = 28), 64% (n = 16), and 80% (n = 35) of patients on pazopanib, bevacizumab, and everolimus, respectively, were managed with continued monitoring at the same dose. The overall incidence of Grades 3 and 4 events was 24% (n = 6) and found in the bevacizumab group. CONCLUSION: A high incidence of proteinuria with minor severity within each class was demonstrated. It may be reasonable to continue therapy at the same dose for Grade 1 or 2 proteinuria. Treatment modification or discontinuation of therapy may be warranted with Grade 3 or 4 proteinuria.

Tolerability of denosumab in metastatic solid tumor patients with renal insufficiency.

PURPOSE: Denosumab is approved for the prevention of skeletal-related events (SREs) in metastatic solid tumor patients with bone metastases. Limited data regarding the safety of denosumab in patients with severe renal insufficiency suggests increased rates of hypocalcemia compared to patients with normal renal function. The purpose of this study was to assess the rates of hypocalcemia and hypophosphatemia in cancer patients with severe renal impairment. METHODS: In this case series, patient demographics, primary tumor site, number of denosumab doses, and episodes of hypocalcemia and hypophosphatemia were retrospectively obtained by patient chart review. Estimated glomerular filtration rate (eGFR) was calculated using the Cockcroft-Gault equation. Twenty-two metastatic solid tumor patients with severe renal insufficiency (creatinine clearance <30 mL/min) who had received denosumab at a dose of 120 mg were included. RESULTS: Ten of 22 patients (45 %) experienced a hypocalcemic event of any grade. Three patients (14 %) had grade 3 hypocalcemia, and no patients had grade 4 hypocalcemia. The median number of doses of denosumab prior to calcium nadir was one. Seven of 22 patients (32 %) experienced hypophosphatemia of any grade including grade 3 events in two patients (9 %). CONCLUSIONS: Denosumab resulted in increased rates of hypocalcemia when administered to metastatic solid tumor patients with severe renal impairment for the prevention of SREs compared to previously reported rates of hypocalcemia in the general population. However, all cases of hypocalcemia were asymptomatic and resolved prior to subsequent dosing. Due to a higher rate of hypocalcemia than reported in patients with normal renal function, patients with severe renal impairment should receive close monitoring of calcium levels while receiving denosumab.

Clinical outcomes for patients with metastatic renal cell carcinoma treated with alternative sunitinib schedules.

PURPOSE: We identified sunitinib alternative schedules that maintained dose intensity while decreasing adverse events in patients with metastatic renal cell cancer. We also determined the impact of alternative schedules on clinical outcomes. MATERIALS AND METHODS: We retrospectively reviewed the records of patients 18 years old or older with clear cell metastatic renal cell cancer who received first line sunitinib between January 26, 2006 and March 1, 2011 at our major comprehensive cancer center. A subset of patients was switched at the first intolerable adverse event from the traditional schedule of 28 days on and 14 days off to a schedule of 14 days on and 7 days off or other alternative schedules. A control group underwent standard dose reduction. We estimated progression-free and overall survival by the Kaplan-Meier method. Predictors of progression-free and overall survival were analyzed using Cox regression. RESULTS: A total of 187 patients were included in analysis, of whom 87% were on the traditional schedule at baseline. During treatment 53% of patients continued on the traditional schedule and 47% began or were transitioned to alternative schedules. Baseline characteristics were similar. Adverse events prompting schedule modification included fatigue in 64% of cases, hand-foot syndrome in 38% and diarrhea in 32%. Median time to alternative schedules was 5.6 months. Median overall survival was 17.7 months (95% CI 10.8-22.2) on the traditional schedule compared to 33.0 months (95% CI 29.3-not estimable) on alternative schedules (p <0.0001). On multivariable analysis poor Eastern Cooperative Oncology Group (ECOG) performance status, increased lactate dehydrogenase, decreased albumin, unfavorable Heng criteria and the traditional schedule were associated with decreased overall survival (p <0.05). CONCLUSIONS: Sunitinib administered on alternative schedules may mitigate adverse events while achieving outcomes comparable to those of the traditional schedule in patients with metastatic renal cell cancer. Prospective investigations of alternate dosing schemas are warranted.

Mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis in patients with renal cell cancer: predictors, management, and outcomes.

OBJECTIVE: To characterise the incidence, onset, management, predictors, and clinical impact of mammalian target of rapamycin (mTOR) inhibitor-associated non-infectious pneumonitis (NIP) on patients with metastatic renal cell carcinoma (mRCC). PATIENTS AND METHODS: Retrospective review of 310 patients with mRCC who received temsirolimus and/or everolimus between June 2007 and October 2010. Clinical correlations were made with serial radiological imaging. Fisher's exact, Wilcoxon rank-sum, and logistic regression analyses were used to evaluate the association of NIP with demographic or clinical factors. Log-rank and Cox proportional hazards regression analyses were used for the time-to-event analysis. RESULTS: NIP occurred in 6% of temsirolimus-treated and 23% of everolimus-treated patients. Symptoms included cough, dyspnoea, and fever (median of two and three symptoms per patient, respectively). The median National Cancer Institute Common Toxicity Criteria for Adverse Events pneumonitis grade was 2 for both groups. Older age and everolimus treatment were predictive of NIP. Patients who developed NIP had a significantly longer time on treatment (median 4.1 vs 2 months) and overall survival (OS) (median 15.4 vs 7.4 months). NIP was a predictor of improved OS by multivariate analysis. CONCLUSIONS: There was an increased incidence of NIP in everolimus-treated patients. Improved OS in patients who developed NIP is an intriguing finding and should be further investigated. Given the incidence, morbidity, and outcomes seen in patients on everolimus who develop NIP, management should include proactive monitoring and treatment of NIP with the goal of preserving mTOR inhibitor therapy.

Opiate prescription after hip and knee arthroplasty: a retrospective cohort study.

AIMS: Excessive opiate analgesia in relation to orthopaedic surgery is associated with morbidity and mortality. Pre-operative use of opiates is associated with higher post-operative use. There is little information about opiate prescribing practices in relation to elective total joint arthroplasty (TJA) in New Zealand rural centres. The aims of this study were to describe opiate use before, immediately after and 1 year after TJA, and to compare prescribing practices with local guidelines. METHODS: A retrospective cohort study of elective primary hip and knee arthroplasties was conducted between January 2018 and April 2019. Opiate use was evaluated from clinical records and from electronic prescribing records and described in morphine milligram equivalents (MME) with a particular focus on pre-operative and post-operative periods, and use after 1 year. RESULTS: In the study period, 199 patients underwent 203 joint arthroplasties. Of these, data from 157 patients were analysed. Patient data were not analysed because of unavailable files (N=20), non-elective procedures (N=11), bilateral arthroplasties (N=4), deaths (N=4) and incomplete information (N=3). Pre-operative opiates were used by 92 (59%) patients, of whom 70 (76%) were not using opiates after 1 year. There were 126 (80%) patients who were discharged with opiate prescriptions and the vast majority, 121 (96%), did not receive discharge prescriptions that conformed to local guidelines. CONCLUSION: Despite undergoing joint arthroplasty, about one quarter of patients who had been prescribed opiates before the operation were still receiving opiates after 1 year. There was poor compliance with local guidelines.

Treatment of metastatic renal carcinoma patients with the combination of gemcitabine, capecitabine and bevacizumab at a tertiary cancer centre.

OBJECTIVE: • 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. METHODS: • 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. RESULTS: • 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. CONCLUSIONS: • 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.

Rhabdomyolysis in a Prostate Cancer Patient Taking Ketoconazole and Simvastatin: Case Report and Review of the Literature.

OBJECTIVE: To report a case of severe rhabdomyolysis resulting in acute renal failure caused by an interaction between ketoconazole and simvastatin in a patient with prostate cancer. CASE SUMMARY: A 64-year-old man who received ketoconazole for prostate cancer, along with simvastatin and fenofibrate for dyslipidemia, presented to our ambulatory clinic with complaints of blood in his urine and weakness following an increase in his ketoconazole dose. Two days after presentation, the patient was admitted with rhabdomyolysis and acute renal failure, as evidenced by elevated serum creatine kinase (>32,000 IU/L), serum myoglobin (20.6 ng/mL), and serum creatinine (4.2 mg/dL) as well as abnormal bone scintigraphy findings. Ketoconazole, fenofibrate, and simvastatin were discontinued. Renal function did not normalize with hydration, and intermittent hemodialysis was initiated; 10 days of hemodialysis resulted in normalization of electrolytes and creatine kinase. Symptom improvement and normalization of laboratory parameters were observed after prolonged hospitalization (24 days). DISCUSSION: Prostate cancer is the most common malignancy among men in the US. Androgen deprivation therapy is the standard initial treatment for biochemical recurrence or metastatic disease. Most patients experience progression to a castrate-resistant disease state, requiring the use of additional therapies. Ketoconazole is considered a secondary hormonal treatment option. We describe an interaction in a patient with prostate cancer between a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor and ketoconazole resulting in rhabdomyolysis, requiring hemodialysis. An objective causality assessment using the Horn Drug Interaction Probability Scale revealed that the adverse drug reaction was a possible result of the interaction. CONCLUSIONS: The temporal fashion in which the episode occurred suggests that a possible simvastatin-ketoconazole interaction precipitated rhabdomyolysis in this patient. The use of ketoconazole for castrate-resistant prostate cancer can lead to drug-drug interactions in patients taking simvastatin or other HMG-CoA reductase inhibitors. Clinicians should be aware of this severe adverse event and take steps to minimize its occurrence.

Implementation of postdischarge follow-up telephone calls at a comprehensive cancer center.

PURPOSE: The development and implementation of a pharmacy-driven, postdischarge follow-up telephone call program to assess medication adherence, provide education, and address medication-related concerns are discussed. SUMMARY: Many readmissions are avoidable through effective discharge planning and patient follow-up after hospitalization. However, there is limited information on how to effectuate this process. To address this barrier, a team consisting of a clinical pharmacy specialist, a clinical pharmacy manager, a postgraduate year 1 pharmacy resident, and an education specialist at The University of Texas MD Anderson Cancer Center collaborated to create a postdischarge telephone call program within a transitions-of-care (TOC) pilot program. Various education and training materials were created to ensure trainees were competent. As of February 2016, 23 outpatient pharmacists and students have completed training, earning a median pretest and posttest score of 6 and 9, respectively, out of 10. There have been 206 calls completed; 150 patients (73%) were successfully reached, and 20 patients (9%) declined the telephone call. Medication adherence assessed during the telephone follow-up identified that 134 patients (89%) received their new medications within 72 hours, and 87 patients (58%) were recognized as having one or more discrepancies. CONCLUSION: Developing a TOC program similar to this pilot program requires several resources including time, collaboration, and support from the management team. Pharmacy is well positioned to complete an accurate medication review and conduct postdischarge telephone calls to address medication-related issues. By providing these services, patients will receive continuity of care and positively impact emergency room visitation rates and hospital readmission rates.

Safety of Same-day Pegfilgrastim Administration in Metastatic Castration-resistant Prostate Cancer Treated With Cabazitaxel With or Without Carboplatin.

INTRODUCTION: Although myeloid growth factors are commonly used to treat metastatic castration-resistant prostate cancer (mCRPC), the optimal timing of administration has not been well studied. We assessed the effects of same-day pegfilgrastim, a neutrophil stimulator, after cabazitaxel treatment with or without carboplatin in patients with mCRPC. We also evaluated the frequency of urinary tract inflammation during treatment. PATIENTS AND METHODS: Between September 2010 and September 2014, 151 consecutive patients with mCRPC underwent cabazitaxel treatment with or without the addition of carboplatin at a single institution. We assessed absolute neutrophil count recovery, incidence of neutropenia, neutropenic fever, antibiotic usage, treatment delays or discontinuation, dose reduction, and hospitalization with pegfilgrastim administration. Radiologists blinded to therapy reviewed computed tomography scans to detect urinary tract inflammation. RESULTS: The median patient age was 69 years (range, 41-88 years); 78% of patients were white, and 54% had a Gleason score ≥ 9. Median overall survival was 9 months (95% confidence interval, 8-11 months). One patient (< 1%) had neutropenia; 38 patients (25%) had infection. During cycle 1, a significantly higher proportion of patients receiving pegfilgrastim after 24 hours developed infection than did those receiving pegfilgrastim the same day (26% vs. 6%; P = .01). CONCLUSION: Same-day pegfilgrastim administration after cabazitaxel treatment with or without carboplatin in patients with mCRPC is feasible. The urinary tract inflammation rate (21%) was higher than that reported anecdotally. Results need to be prospectively validated.

Impact of Statin Use on Outcomes in Triple Negative Breast Cancer.

Purpose: We sought to investigate if the use of HMG Co-A reductase inhibitors (statins) has an impact on outcomes among patients with triple negative breast cancer (TNBC). Methods: We reviewed the cases of women with invasive, non-metastatic TNBC, diagnosed 1997-2012. Clinical outcomes were compared based on statin use (defined as ever use during treatment vs. never use). We identified a subset of women for whom a 5-value lipid panel (5VLP) was available, including total cholesterol, low density lipoprotein, high density lipoprotein, very low density lipoprotein, and triglycerides. The Kaplan-Meier method was used to estimate median overall survival (OS), distant metastases-free survival (DMFS), and local-regional recurrence-free survival (LRRFS). A Cox proportional hazards regression model was used to test the statistical significance of prognostic factors. Results: 869 women were identified who met inclusion criteria, with a median follow-up time of 75.1 months (range 2.4-228.9 months). 293 (33.7%) patients used statins and 368 (42.3%) had a 5VLP. OS, DMFS, and LRRFS were not significant based on statin use or type. Controlling for the 5VLP values, on multivariable analysis, statin use was significantly associated with OS (HR 0.10, 95% CI 0.01-0.76), but not with DMFS (HR 0.14, 95% CI 0.01-1.40) nor LRRFS (HR 0.10 95% CI 0.00-3.51). Conclusions: Statin use among patients with TNBC is not associated with improved OS, although it may have a benefit for a subset of patients. Prospective assessment would be valuable to better assess the potential complex correlation between clinical outcome, lipid levels, and statin use.

Outcomes of Patients With Metastatic Non-Clear-Cell Renal Cell Carcinoma Treated With Pazopanib.

BACKGROUND: Pazopanib is associated with increased progression-free survival (PFS) in clear-cell renal cell carcinoma (RCC) and has become a standard of care in this disease. The drug is used in metastatic non-clear-cell RCC, but data on outcomes in this setting are limited. PATIENTS AND METHODS: We conducted a retrospective data analysis of records of consecutive metastatic non-clear-cell RCC patients who received pazopanib in front-line and salvage settings between November 2009 and November 2012. Tumor response rate was assessed by a blinded radiologist using Response Evaluation Criteria in Solid Tumors version 1.1. PFS and overall survival (OS) times were estimated using Kaplan-Meier methods. RESULTS: Twenty-nine patients were identified with non-clear-cell metastatic RCC, 9 received pazopanib in the front-line setting, 20 in the salvage setting after progression of disease with other targeted therapies. Seven patients (24%) had papillary RCC, 4 (14%) had chromophobe, 5 (17%) had unclassified histopathology, and 13 (45%) had other subtypes including collecting duct, translocation Xp11.2, and various subtypes with sarcomatoid differentiation. All patients discontinued pazopanib before analysis. Median PFS was 8.1 months (95% CI, 5.7-NA [not available]) in the front-line group, and 4 months (95% CI, 2.1-9.9) in the salvage group. Median OS was 31 months (95% CI, 9.2-NA) in the front-line group, and 13.6 months (95% CI, 6.4-NA) in the salvage group. CONCLUSION: Pazopanib showed efficacy in patients with metastatic non-clear-cell RCC in the front-line and salvage settings. Toxicity was mild to moderate and manageable. Further studies are needed to evaluate pazopanib's role in non-clear-cell RCC in terms of efficacy and safety.

Outcomes of Patients With Metastatic Renal Cell Carcinoma and Bone Metastases in the Targeted Therapy Era.

BACKGROUND: Bone metastases (BMs) occur commonly in patients with metastatic renal cell carcinoma (mRCC). Tyrosine kinase inhibitors (TKIs) have improved the outcomes for patients with mRCC. However, data on the outcomes of mRCC patients with BMs treated with TKIs are limited. We describe the outcomes of patients with BMs treated with TKI therapy and compare them with the outcomes from a pre-TKI group. PATIENTS AND METHODS: Using an institutional tumor registry, a retrospective review of patients with mRCC from 2002 to 2003 and 2006 to 2007 was performed. The baseline characteristics were analyzed, and overall survival (OS) was estimated using the Kaplan-Meier method. The predictors of OS were analyzed using Cox regression analysis. RESULTS: The data from 375 patients were reviewed. Of these patients, 188 (50%) started treatment with TKIs and 187 (50%) had started treatment in the pre-TKI era. The distribution of patient characteristics was similar. The sites of organ metastases were equally distributed, including BMs in 48% of the patients in each cohort. The median OS for the patients treated in the TKI era was 22 months (95% confidence interval [CI], 17-25 months) compared with 14 months (95% CI, 10-19 months; P < .01) for the historical controls. A subset analysis of patients with BM in the TKI era demonstrated a median OS of 24 months (95% CI, 17-28 months) compared with 18 months (95% CI, 10-21 months; P < .01) in pre-TKI era. The predictors of shorter OS were a higher Memorial Sloan Kettering Cancer Center score; liver, lung, and brain metastases; and multiple sites of BMs (hazard ratio, 1.38; 95% CI, 1.02-1.91; P = .04). The rate of new BM development was the same in the pre- and post-TKI era. CONCLUSION: The rate of BM development was the same in the pre- and post-TKI era. The management of BMs in patients with mRCC remains challenging.

High-density and very-low-density lipoprotein have opposing roles in regulating tumor-initiating cells and sensitivity to radiation in inflammatory breast cancer.

PURPOSE: We previously demonstrated that cholesterol-lowering agents regulate radiation sensitivity of inflammatory breast cancer (IBC) cell lines in vitro and are associated with less radiation resistance among IBC patients who undergo postmastectomy radiation. We hypothesized that decreasing IBC cellular cholesterol induced by treatment with lipoproteins would increase radiation sensitivity. Here, we examined the impact of specific transporters of cholesterol (ie lipoproteins) on the responses of IBC cells to self-renewal and to radiation in vitro and on clinical outcomes in IBC patients. METHODS AND MATERIALS: Two patient-derived IBC cell lines, SUM 149 and KPL4, were incubated with low-density lipoproteins (LDL), very-low-density lipoproteins (VLDL), or high-density lipoproteins (HDL) for 24 hours prior to irradiation (0-6 Gy) and mammosphere formation assay. Cholesterol panels were examined in a cohort of patients with primary IBC diagnosed between 1995 and 2011 at MD Anderson Cancer Center. Lipoprotein levels were then correlated to patient outcome, using the log rank statistical model, and examined in multivariate analysis using Cox regression. RESULTS: VLDL increased and HDL decreased mammosphere formation compared to untreated SUM 149 and KPL4 cells. Survival curves showed enhancement of survival in both of the IBC cell lines when pretreated with VLDL and, conversely, radiation sensitization in all cell lines when pretreated with HDL. In IBC patients, higher VLDL values (>30 mg/dL) predicted a lower 5-year overall survival rate than normal values (hazard ratio [HR] = 1.9 [95% confidence interval [CI]: 1.05-3.45], P=.035). Lower-than-normal patient HDL values (<60 mg/dL) predicted a lower 5-year overall survival rate than values higher than 60 mg/dL (HR = 3.21 [95% CI: 1.25-8.27], P=.015). CONCLUSIONS: This study discovered a relationship among the plasma levels of lipoproteins, overall patient response, and radiation resistance in IBC patients and IBC patient-derived cell lines. A more expansive study is needed to verify these observations.

Outcomes of patients with metastatic renal cell carcinoma and end-stage renal disease receiving dialysis and targeted therapies: a single institution experience.

INTRODUCTION: Limited data are available regarding patients with renal cell carcinoma and ESRD treated with TTs. The objective of this study was to explore the tolerability and safety of TT in patients with mRCC and ESRD. PATIENTS AND METHODS: We retrospectively identified patients with mRCC and ESRD treated at the University of Texas M.D. Anderson Cancer Center from 2002 to 2012. Patient characteristics including demographic, histology, treatment, and adverse events are reported. Duration of treatment (TOT) was determined from date of drug initiation to discontinuation. Overall survival (OS) was determined from initiation of TT to death. Statistics are descriptive. RESULTS: Fourteen patients were identified. Ten patients had clear-cell histology and 4 had papillary histology. The median number of TTs per patient was 3 (range, 1-4) with median TOT of 28 months for all TTs. Eighty-eight percent of all toxicities were Grade 1 to 2; no Grade 4 toxicities were noted. Treatment discontinuations included 3 patients treated with sorafenib due to hand-foot syndrome, intolerable fatigue, and squamous cell skin cancer development; 2 patients treated with pazopanib due to intolerable fatigue and increased transaminase levels; and 1 patient treated with everolimus due to pneumonitis. Eight patients died from progressive disease. Median OS from initiation of TT was 28.5 months and 35 months from time of diagnosis. CONCLUSION: Toxicities were mild to moderate and consistent with those reported in previous studies. TTs appear to be safe, well tolerated and produce antitumor response in patients with mRCC and ESRD receiving dialysis.

Screening for prostate cancer: the debate continues.

Other than skin cancer, prostate cancer is the most frequently diagnosed cancer in men, and it is the second leading cause of cancer-related death for males in the United States. Screening for prostate cancer using prostate-specific antigen testing became widely used by the late 1980s, augmenting the digital rectal exam. This led to a decline in the percentage of prostate cancer cases that were metastatic at diagnosis and a decrease in prostate cancer mortality. But some argued it led to overtreatment of prostate cancers as well. Recently, the U.S. Preventive Services Task Force (USPSTF) issued recommendations against routine prostate cancer screening in asymptomatic patients. The recent recommendations have created much controversy among medical professionals, patient advocate groups, and the general public. Most prostate cancer screening recommendations from professional organizations agree that an informed discussion and review of each individual patient's clinical situation should drive the decision to screen or not to screen, but the current USPSTF recommendations largely remove patient and provider autonomy in this regard. They do not contribute toward personalized screening based on individualized patient risk profiles, characteristics, and preferences.

The impact of an outpatient palliative care consultation on symptom burden in advanced prostate cancer patients.

OBJECTIVES: There are limited studies characterizing cancer-related symptoms in outpatient advanced prostate cancer patients. The aim of this retrospective study was to describe the impact of an outpatient palliative care (PC) consultation on symptoms in patients with advanced prostate cancer. METHODS: We retrospectively reviewed the medical records of 55 consecutive patients with advanced prostate cancer seen in our institution's outpatient PC center. Information regarding demographics, disease status, Edmonton Symptom Assessment System (ESAS) scores, Eastern Cooperative Oncology Group (ECOG) Performance Status, laboratory data, and pharmacological interventions were analyzed. RESULTS: The median age of the study's patients was 66 years old, with 73% Caucasian ethnicity. All patients had metastatic disease and 96% had received prior cytotoxic chemotherapy. The most frequently occurring symptoms upon presentation were pain, fatigue, and drowsiness (>50%). Pain and fatigue were also the most severe symptoms, each having median ESAS scores of 7 (on a 0-10 scale). We instituted a median of 3 pharmacological interventions per patient, with a median of 15 days to follow-up assessment. At follow-up, patients reported significant symptom improvements in pain, drowsiness, fatigue, depression, sleep, sense of well-being, and anxiety. CONCLUSIONS: Based on our preliminary data, we conclude that patients with advanced prostate cancer referred to PC experience severe and clinically significant symptoms. An outpatient PCconsultation is associated with significant symptom improvement in this subset of a distressed population. Future prospective studies are warranted to further describe symptom burden and the role for outpatient PC for advanced prostate cancer patients.