Hao-Wen Sim

Outcomes of Metastatic Chromophobe Renal Cell Carcinoma (chrRCC) in the Targeted Therapy Era: Results from the International Metastatic Renal Cell Cancer Database Consortium (IMDC)

Background: Treatment outcomes are poorly characterized in patients with metastatic chromophobe renal cell cancer (chrRCC), a subtype of renal cell carcinoma. Objective: This retrospective series aims to determine metastatic chrRCC treatment outcomes in the targeted therapy era. Methods: A retrospective data analysis was performed using the IMDC dataset of 4970 patients to determine metastatic chrRCC treatment outcomes in the targeted therapy era. Results: 109/4970 (2.2%) patients had metastatic chrRCC out of all patients with mRCC treated with targeted therapy. These patients were compared with 4861/4970 (97.8%) clear cell mRCC (ccRCC) patients. Patients with metastatic chrRCC had a similar OS compared to patients with ccRCC (23.8 months (95% CI 16.7 – 28.1) vs 22.4 months (95% CI 21.4 – 23.4), respectively (p = 0.0908). Patients with IMDC favorable (18%), intermediate (59%) and poor risk (23%) had median overall survivals of 31.4, 27.3, and 4.8 months, respectively (p = 0.028). Conclusions: To the authors’ knowledge, this is the largest series of metastatic chrRCC patients and these results set new benchmarks for survival in clinical trial design and patient counseling. The IMDC criteria risk categories seem to stratify patients into appropriate favourable, intermediate, and poor risk groups, although larger patient numbers are required. It appears that outcomes between metastatic chrRCC and ccRCC are similar when treated with conventional targeted therapies. Patients with metastatic chrRCC can be treated with tyrosine kinase inhibitors and enrolled in clinical trials to further measure outcomes in this rare patient population.

Systematic review of interventions to facilitate advance care planning (ACP) in cancer patients.

21 Background: ACP refers to the process of consideration, documentation and communication of preferences for future care. ACP is crucial for patients (pts) with advanced cancer as it can guide substitute decision makers (SDM) and health care providers (HCP) to align care with preferences, thus improving quality of end-of-life care. METHODS We performed a systematic review of MEDLINE, EMBASE, CINAHL, PsycINFO and Cochrane (Systematic Review and Clinical Trial) databases (1995 to 2015) to identify interventions that facilitate ACP for cancer pts (documentation or discussion of advance directives, SDM or code status). We extracted data on study design, setting, subject numbers, interventions and outcomes. Study quality was assessed using a modified Downs and Black checklist. RESULTS Of the 64,196 unique citations identified, 10 studies met inclusion criteria for testing interventions using a pre-post or controlled trial design (median sample size 134, range 48-9105). Interventions were categorized based on target audience: health system (n = 4), pts and caregivers (n = 3) or HCP (n = 3). Types of interventions included: introduction of ACP facilitators (n = 4), reminders or prompts (n = 2), and HCP training, videos, website or pt screening (n = 1 each). Heterogeneity in study design, outcome measures and small sample sizes limited study quality and precluded meta-analysis. Prompts such as medical record or email reminders were most consistently associated with improved ACP documentation. System changes incorporating the use of ACP facilitators also improved ACP documentation in 3 out of 4 studies. Interactive HCP training significantly improved confidence to initiate ACP discussions which has been identified as a barrier to timely ACP. Pilot trials showed no significant increase in ACP with educational videos/websites directed at pts. Passive HCP education and one-off reminders were also ineffective. CONCLUSIONS The complexity of ACP is reflected in the multitude of interventions that have been evaluated but none are ready for wide-scale adoption. Further studies of interventions such as prompts and ACP facilitators are needed to inform the best approach to improve ACP uptake in cancer pts.

Active Smoking Is Associated With Worse Prognosis in Metastatic Renal Cell Carcinoma Patients Treated With Targeted Therapies

Background Smoking increases the risk of developing renal cell carcinoma (RCC) but the effect of tobacco consumption on survival outcome of patients with metastatic RCC (mRCC) treated with targeted therapies has not been well characterized. Patients and Methods The primary outcome was overall survival (OS) and secondary outcome was progression‐free survival (PFS). Patients with mRCC were categorized as current, former, and nonsmokers at the time of starting targeted therapy. Smoking data from 1980 patients with mRCC treated with targeted therapy were collected through the International mRCC Database Consortium (IMDC) from 12 international cancer centers. Results Although former and nonsmokers had comparable OS times (23.8 vs. 23.4 months; P = .898), current smokers had significantly shorter OS (16.1 months; P < .001) than nonsmokers. Current but not former smoking status was an independent poor prognosis factor (hazard ratio [HR], 1.3; P = .002) when adjusted for the IMDC risk criteria. Each pack‐year increased the risk of death by 1% (HR, 1.01; P = .036). The duration of first‐line therapy response was not different and was 7.7 months versus 7.5 months versus 6.4 months in never, former (P = .609), and current smokers (P = .839), respectively. Conclusion Active smoking is associated with diminished OS in mRCC patients treated with targeted therapy agents. However, patients who quit smoking returned to a similar risk of death from RCC compared with patients who never smoked. Smoking cessation should be a counseling priority among mRCC patients receiving targeted agents and smoking should be considered as a confounding factor in major clinical trials. Micro‐Abstract It is well known that tobacco smoking is a modifiable risk factor that increases the risk of renal cell carcinoma (RCC) development. Previous studies with patients who were mainly treated with traditional immunotherapies have suggested that tobacco smoking also negatively affects RCC patients’ overall and cancer‐specific survival. The current study showed that active smoking leads to a significant shorter overall survival in RCC patients treated with targeted therapies whereas patients who had stopped smoking had a risk for death comparable with patients who had never smoked. Moreover, the amount of tobacco smoking is a continuous risk factor for an early death in RCC patients treated with targeted therapies. Smoking cessation is an important part of the treatment management of RCC patients.

Prognosis of patients with hepatocellular carcinoma treated with sorafenib: a comparison of five models in a large Canadian database

Several systems (tumor‐node‐metastasis [TNM], Barcelona Clinic Liver Cancer [BCLC], Okuda, Cancer of the Liver Italian Program [CLIP], and albumin–bilirubin grade [ALBI]) were developed to estimate the prognosis of patients with hepatocellular carcinoma (HCC) mostly prior to the prevalent use of sorafenib. We aimed to compare the prognostic and discriminatory power of these models in predicting survival for HCC patients treated with sorafenib and to identify independent prognostic factors for survival in this population. Patients who received sorafenib for the treatment of HCC between 1 January 2008 and 30 June 2015 in the provinces of British Columbia and Alberta, and two large cancer centers in Toronto, Ontario, were included. Survival was assessed using the Kaplan–Meier method. Multivariate Cox regression was used to identify predictors of survival. The models were compared with respect to homogeneity, discriminatory ability, monotonicity of gradients, time‐dependent area under the curve, and Akaike information criterion. A total of 681 patients were included. 80% were males, 86% had Child–Pugh class A, and 37% of patients were East Asians. The most common etiology for liver disease was hepatitis B (34%) and C (31%). In all model comparisons, CLIP performed better while BCLC and TNM7 performed less favorably but the differences were small. The utility of each system in allocating patients into different prognostic groups varied, for example, TNM poorly differentiated patients in advanced stages (8.7 months (m) (95% CI 6.5–11.5) versus 8.4 m (95% CI 7.0–9.6) for stages III and IV, respectively) while ALBI had excellent discrimination of early grades (15.6 m [95% CI 13.0–18.4] versus 8.3 m [95% CI 7.0–9.2] for grades 1 and 2, respectively). On multivariate analysis, hepatitis C, alcoholism, and prior hepatic resection were independently prognostic of better survival (P < 0.01). In conclusion, none of the prognostic systems was optimal in predicting survival in sorafenib‐treated patients with HCC. Etiology of liver disease should be considered in future models and clinical trial designs.

An Update on Randomized Clinical Trials in Hepatocellular Carcinoma

Hepatocellular carcinoma is a common malignancy that typically occurs in the setting of comorbid liver disease. Optimal management is challenging, especially given the assortment of available treatment modalities. This article reviews the randomized clinical trials that have formed the basis of contemporary hepatocellular carcinoma management.