Scott Ernst

A randomized trial of external beam radiotherapy versus cryoablation in patients with localized prostate cancer

Localized prostate cancer can be treated several different ways, but head‐to‐head comparisons of treatments are infrequent. The authors of this report conducted a randomized, unblinded, noninferiority trial to compare cryoablation with external beam radiotherapy in these patients.

Detection of circulating tumor cells in advanced head and neck cancer using the cellsearch system

Early detection of circulating tumor cells (CTCs) offers the possibility of improved outcome for patients with head and neck squamous cell cancer (HNSCC).

The epidemic of human papillomavirus and oropharyngeal cancer in a Canadian population

BACKGROUND Sexually transmitted infection with the human papillomavirus (hpv) is responsible for a significant burden of human cancers involving the cervix, anogenital tract, and oropharynx. Studies in the United States and Europe have demonstrated an alarming increase in the frequency of hpv-positive oropharyngeal cancer, but the same direct evidence does not exist in Canada. METHODS Using the London Health Sciences Centre pathology database, we identified tonsillar cancers diagnosed between 1993 and 2011. Real-time polymerase chain reaction was then used on pre-treatment primary-site biopsy samples to test for dna from the high-risk hpv types 16 and 18. The study cohort was divided into three time periods: 1993-1999, 2000-2005, and 2006-2011. RESULTS Of 160 tumour samples identified, 91 (57%) were positive for hpv 16. The total number of tonsillar cancers significantly increased from 1993-1999 to 2006-2011 (32 vs. 68), and the proportion of cases that were hpv-positive substantially increased (25% vs. 62%, p < 0.002). Those changes were associated with a marked improvement in 5-year overall survival (39% in 1993-1999 vs. 84% in 2006-2011, p < 0.001). When all factors were included in a multivariable model, only hpv status predicted treatment outcome. INTERPRETATION The present study is the first to provide direct evidence that hpv-related oropharyngeal cancer is increasing in incidence in a Canadian population. Given the long lag time between hpv infection and clinically apparent malignancy, oropharyngeal cancer will be a significant clinical problem for the foreseeable future despite vaccination efforts.

Testing personalized medicine: patient and physician expectations of next-generation genomic sequencing in late-stage cancer care

Developments in genomics, including next-generation sequencing technologies, are expected to enable a more personalized approach to clinical care, with improved risk stratification and treatment selection. In oncology, personalized medicine is particularly advanced and increasingly used to identify oncogenic variants in tumor tissue that predict responsiveness to specific drugs. Yet, the translational research needed to validate these technologies will be conducted in patients with late-stage cancer and is expected to produce results of variable clinical significance and incidentally identify genetic risks. To explore the experiential context in which much of personalized cancer care will be developed and evaluated, we conducted a qualitative interview study alongside a pilot feasibility study of targeted DNA sequencing of metastatic tumor biopsies in adult patients with advanced solid malignancies. We recruited 29/73 patients and 14/17 physicians; transcripts from semi-structured interviews were analyzed for thematic patterns using an interpretive descriptive approach. Patient hopes of benefit from research participation were enhanced by the promise of novel and targeted treatment but challenged by non-findings or by limited access to relevant trials. Family obligations informed a willingness to receive genetic information, which was perceived as burdensome given disease stage or as inconsequential given faced challenges. Physicians were optimistic about long-term potential but conservative about immediate benefits and mindful of elevated patient expectations; consent and counseling processes were expected to mitigate challenges from incidental findings. These findings suggest the need for information and decision tools to support physicians in communicating realistic prospects of benefit, and for cautious approaches to the generation of incidental genetic information.

A Randomized Trial of External Beam Radiotherapy Versus Cryoablation in Patients With Localized Prostate Cancer: Quality of Life Outcomes

A recent randomized trial to compare external beam radiation therapy (EBRT) to cryoablation for localized disease showed cryoablation to be noninferior to external beam EBRT in disease progression and overall and disease‐specific survival. We report on the quality of life (QOL) outcomes for this trial.

Characterization and Management of Hedgehog Pathway Inhibitor-Related Adverse Events in Patients With Advanced Basal Cell Carcinoma

Vismodegib and sonidegib are Hedgehog pathway inhibitors (HPIs) approved for treatment of patients with advanced basal cell carcinoma. The adverse events (AEs) associated with these therapies can impact clinical outcomes as a result of decreased quality of life and treatment discontinuation. The incidence, clinical presentation, putative mechanisms, and management strategies for AEs related to administration of HPIs are described in this article.

Outcome of Patients With Metastatic Sarcomatoid Renal Cell Carcinoma: Results From the International Metastatic Renal Cell Carcinoma Database Consortium

BACKGROUND Sarcomatoid renal cell carcinoma is associated with poor prognosis. Data regarding outcome in the targeted therapy era are lacking. PATIENTS AND METHODS Clinical, prognostic, and treatment parameters in metastatic renal cell carcinoma patients with and without sarcomatoid histology treated with targeted therapy were retrospectively analyzed. RESULTS Two thousand two hundred eighty-six patients were identified (sRCC: n = 230 and non-sRCC: n = 2056). sRCC patients had significantly worse IMDC prognostic criteria compared with non-sRCC (11% vs. 19% favorable risk; 49% vs. 57% intermediate risk, and 40% vs. 24% poor risk; P < .0001). Time from original diagnosis to relapse (excluding synchronous metastatic disease) was shorter in the sRCC group (18.8 vs. 42.9 months; P < .0001). There was no significant difference in the incidence of central nervous system metastases (6%-8%) or underlying clear cell histology (87%-88%). More than 93% of patients received VEGF inhibitors as first-line therapy; objective response was less common in sRCC whereas primary refractory disease was more common (21% vs. 26% and 43% vs. 21%; P < .0001, for both). sRCC patients had significantly less use of second- (P = .018) and third-line (P < .0001) systemic therapy. The median progression-free survival (PFS)/overall survival (OS) was 4.5/10.4 months in sRCC patients and 7.8/22.5 months in non-sRCC patients (P < .0001 for both). Sarcomatoid histology was associated with a significantly worse PFS and OS after adjusting for individual IMDC risk factors in multivariable analysis (hazard ratio, 1.5; P < .0001 for both). CONCLUSION Patients with sRCC have a shorter time to relapse, worse baseline prognostic criteria, and worse clinical outcome with targeted therapy. Additional insight into the biology of sRCC is needed to develop alternative therapeutics.

Does HPV type affect outcome in oropharyngeal cancer

BackgroundAn epidemic of human papillomavirus (HPV)-related oropharyngeal squamous cell cancer (OPSCC) has been reported worldwide largely due to oral infection with HPV type-16, which is responsible for approximately 90% of HPV-positive cases. The purpose of this study was to determine the rate of HPV-positive oropharyngeal cancer in Southwestern Ontario, Canada.MethodsA retrospective search identified ninety-five patients diagnosed with OPSCC. Pre-treatment biopsy specimens were tested for p16 expression using immunohistochemistry and for HPV-16, HPV-18 and other high-risk subtypes, including 31,33,35,39,45,51,52,56,58,59,67,68, by real-time qPCR.ResultsFifty-nine tumours (62%) were positive for p16 expression and fifty (53%) were positive for known high-risk HPV types. Of the latter, 45 tumors (90%) were identified as HPV-16 positive, and five tumors (10%) were positive for other high-risk HPV types (HPV-18 (2), HPV-67 (2), HPV-33 (1)). HPV status by qPCR and p16 expression were extremely tightly correlated (p < 0.001, Fishers exact test). Patients with HPV-positive tumors had improved 3-year overall (OS) and disease-free survival (DFS) compared to patients with HPV-negative tumors (90% vs 65%, p = 0.001; and 85% vs 49%, p = 0.005; respectively). HPV-16 related OPSCC presented with cervical metastases more frequently than other high-risk HPV types (p = 0.005) and poorer disease-free survival was observed, although this was not statistically significant.ConclusionHPV-16 infection is responsible for a significant proportion of OPSCC in Southwestern Ontario. Other high-risk subtypes are responsible for a smaller subset of OPSCC that present less frequently with cervical metastases and may have a different prognosis.

Body Mass Index and Metastatic Renal Cell Carcinoma: Clinical and Biological Correlations.

PURPOSE Obesity is an established risk factor for clear cell renal cell carcinoma (RCC); however, some reports suggest that RCC developing in obese patients may be more indolent. We investigated the clinical and biologic effect of body mass index (BMI) on treatment outcomes in patients with metastatic RCC. METHODS The impact of BMI (high BMI: ≥ 25 kg/m2 v low BMI: < 25 kg/m2) on overall survival (OS) and treatment outcome with targeted therapy was investigated in 1,975 patients from the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) and in an external validation cohort of 4,657 patients. Gene expression profiling focusing on fatty acid metabolism pathway, in The Cancer Genome Atlas data set, and immunohistochemistry staining for fatty acid synthase (FASN) were also investigated. Cox regression was undertaken to estimate the association of BMI with OS, adjusted for the IMDC prognostic factors. RESULTS In the IMDC cohort, median OS was 25.6 months (95% CI, 23.2 to 28.6) in patients with high BMI versus 17.1 months (95% CI, 15.5 to 18.5) in patients with low BMI (adjusted hazard ratio, 0.84; 95% CI, 0.73 to 0.95). In the validation cohort, high BMI was associated with improved OS (adjusted hazard ratio, 0.83; 95% CI, 0.74 to 0.93; medians: 23.4 months [95% CI, 21.9 to 25.3 months] v 14.5 months [95% CI, 13.8 to 15.9 months], respectively). In The Cancer Genome Atlas data set (n = 61), FASN gene expression inversely correlated with BMI (P = .034), and OS was longer in the low FASN expression group (medians: 36.8 v 15.0 months; P = .002). FASN immunohistochemistry positivity was more frequently detected in IMDC poor (48%) and intermediate (34%) risk groups than in the favorable risk group (17%; P-trend = .015). CONCLUSION High BMI is a prognostic factor for improved survival and progression-free survival in patients with metastatic RCC treated with targeted therapy. Underlying biology suggests a role for the FASN pathway.

Management of small cell carcinoma of the bladder: Consensus guidelines from the Canadian Association of Genitourinary Medical Oncologists (CAGMO).

Small cell carcinomas (SCC) most commonly arise from the lung.1 These tumours are aggressive, present with early metastasis and are associated with a poorer prognosis compared to non-small cell lung cancer.2,3 Extra-pulmonary SCC was first described by Duguid and Kennedy in 19304 and subsequently has been reported in the gastrointestinal tract,5 head and neck6 and genitourinary (GU) system.7 SCC of the GU system (SCCGU) are uncommon, but can occur in the kidneys,8 renal pelvis,9 ureter,10 bladder,7 urachus,11 urethra12 and prostate.13 Although rare, these cancers are not insignificant. SCC accounts for 0.5% to 0.7% of all bladder cancers diagnosed.14,15 SCCGU also behaves more aggressively than typical GU histological counterparts.16 There is little medical literature to guide the optimal management of SCCGU malignancies and therefore treatment paradigms have by default mirrored those of the more common small cell carcinoma of the lung. Given the rarity of SCCGU tract and the lack of good clinical guidelines, it was clear that a guideline to help Canadian physicians and surgeons manage these patients with SCCGU was needed. This document achieves that goal for small cell carcinoma of the bladder (SCCB).