Clinical validation of circulating GDF15/MIC-1 as a marker of response to docetaxel and survival in men with metastatic castration-resistant prostate cancer.

BACKGROUND: Elevated circulating growth differentiation factor (GDF15/MIC-1), interleukin 4 (IL4), and IL6 levels were associated with resistance to docetaxel in an exploratory cohort of men with metastatic castration-resistant prostate cancer (mCRPC). This study aimed to establish level 2 evidence of cytokine biomarker utility in mCRPC. METHODS: IntVal: Plasma samples at baseline (BL) and Day 21 docetaxel (n = 120). ExtVal: Serum samples at BL and Day 42 of docetaxel (n = 430). IL4, IL6, and GDF15 levels were measured by ELISA. Monocytes and dendritic cells were treated with 10% plasma from men with high or low GDF15 or recombinant GDF15. RESULTS: IntVal: Higher GDF15 levels at BL and Day 21 were associated with shorter overall survival (OS) (BL; p = 0.03 and Day 21; p = 0.004). IL4 and IL6 were not associated with outcomes. ExtVal: Higher GDF15 levels at BL and Day 42 predicted shorter OS (BL; p < 0.0001 and Day 42; p < 0.0001). Plasma from men with high GDF15 caused an increase in CD86 expression on monocytes (p = 0.03), but was not replicated by recombinant GDF15. CONCLUSIONS: Elevated circulating GDF15 is associated with poor prognosis in men with mCRPC receiving docetaxel and may be a marker of changes in the innate immune system in response to docetaxel resistance. These findings provide a strong rationale to consider GDF15 as a biomarker to guide a therapeutic trial of drugs targeting the innate immune system in combination with docetaxel in mCRPC.

Combined impact of lipidomic and genetic aberrations on clinical outcomes in metastatic castration-resistant prostate cancer.

BACKGROUND: Both changes in circulating lipids represented by a validated poor prognostic 3-lipid signature (3LS) and somatic tumour genetic aberrations are individually associated with worse clinical outcomes in men with metastatic castration-resistant prostate cancer (mCRPC). A key question is how the lipid environment and the cancer genome are interrelated in order to exploit this therapeutically. We assessed the association between the poor prognostic 3-lipid signature (3LS), somatic genetic aberrations and clinical outcomes in mCRPC. METHODS: We performed plasma lipidomic analysis and cell-free DNA (cfDNA) sequencing on 106 men with mCRPC commencing docetaxel, cabazitaxel, abiraterone or enzalutamide (discovery cohort) and 94 men with mCRPC commencing docetaxel (validation cohort). Differences in lipid levels between men ± somatic genetic aberrations were assessed with t-tests. Associations between the 3LS and genetic aberrations with overall survival (OS) were examined using Kaplan-Meier methods and Cox proportional hazard models. RESULTS: The 3LS was associated with shorter OS in the discovery (hazard ratio [HR] 2.15, 95% confidence interval [CI] 1.4-3.3, p < 0.001) and validation cohorts (HR 2.32, 95% CI 1.59-3.38, p < 0.001). Elevated plasma sphingolipids were associated with AR, TP53, RB1 and PI3K aberrations (p < 0.05). Men with both the 3LS and aberrations in AR, TP53, RB1 or PI3K had shorter OS than men with neither in both cohorts (p ≤ 0.001). The presence of 3LS and/or genetic aberration was independently associated with shorter OS for men with AR, TP53, RB1 and PI3K aberrations (p < 0.02). Furthermore, aggressive-variant prostate cancer (AVPC), defined as 2 or more aberrations in TP53, RB1 and/or PTEN, was associated with elevated sphingolipids. The combination of AVPC and 3LS predicted for a median survival of ~12 months. The relatively small sample size of the cohorts limits clinical applicability and warrants future studies. CONCLUSIONS: Elevated circulating sphingolipids were associated with AR, TP53, RB1, PI3K and AVPC aberrations in mCRPC, and the combination of lipid and genetic abnormalities conferred a worse prognosis. These findings suggest that certain genotypes in mCRPC may benefit from metabolic therapies.

An analysis of a multiple biomarker panel to better predict prostate cancer metastasis after radical prostatectomy.

A plethora of individual candidate biomarkers for predicting biochemical relapse in localized prostate cancer (PCa) have been proposed. Combined biomarkers may improve prognostication, and ensuring validation against more clinically relevant endpoints are required. The Australian PCa Research Centre NSW has contributed to numerous studies of molecular biomarkers associated with biochemical relapse. In the current study, these biomarkers were re-analyzed for biochemical relapse, metastatic relapse and PCa death with extended follow-up. Biomarkers of significance were then used to develop a combined prognostic model for clinical outcomes and validated in a large independent cohort. The discovery cohort (n = 324) was based on 12 biomarkers with a median follow-up of 16 years. Seven biomarkers were significantly associated with biochemical relapse. Three biomarkers were associated with metastases: AZGP1, Ki67 and PML. Only AZGP1 was associated with PCa death. In their individual and combinational forms, AZGP1 and Ki67 as a dual BM signature was the most robust predictor of metastatic relapse (AUC 0.762). The AZPG1 and Ki67 signature was validated in an independent cohort of 347 PCa patients. The dual BM signature of AZGP1 and Ki67 predicted metastasis in the univariable (HR 7.2, 95% CI, 1.6-32; p = 0.01) and multivariable analysis (HR 5.4, 95% CI, 1.2-25; p = 0.03). The dual biomarker signature marginally improved risk prediction compared to AZGP1 alone (AUC 0.758 versus 0.738, p < 0.001). Our findings indicate that biochemical relapse is not an adequate surrogate for metastasis or PCa death. The dual biomarker signature of AZGP1 and Ki67 offers a small benefit in predicting metastasis over AZGP1 alone.

p53 nuclear accumulation as an early indicator of lethal prostate cancer.

BACKGROUND: After radical prostatectomy (RP) for prostate cancer (PC), p53 alterations predict biochemical relapse (BCR), however, recent evidence suggests that metastatic relapse (MR) not BCR is a surrogate for PC specific mortality (PCSM). This updated analysis of a previously published study investigated the association between p53 aberrations, MR and PCSM in men with localised PC. METHODS: Two hundred and seventy-one men with localised PC treated with RP were included. RP specimens stained for p53 by immunohistochemistry were scored as (a) percentage of p53-positive tumour nuclei; and (b) clustering, where ≥12 p53-positive cells within a ×200 power field was deemed 'cluster positive'. Associations between p53 status and clinical outcomes (BCR, MR and PCSM) were evaluated. RESULTS: Increasing percentage of p53-positive nuclei was significantly associated with shorter time to BCR, MR and PCSM (All p < 0.001). Half of the patients were p53 cluster positive. p53 cluster positivity was significantly associated with poorer outcomes at all clinical endpoints (BCR: HR 2.0, 95% CI 1.51-2.65, p < 0.001; MR: HR 4.1, 95% CI 2.02-8.14, p < 0.001; PCSM: HR 12.2, 95% CI 1.6-93; p = 0.016). These associations were independent of other established prognostic variables. CONCLUSIONS: p53 aberrations in radical prostatectomy tissue predict clinically relevant endpoints of MR and PCSM.

A distinct plasma lipid signature associated with poor prognosis in castration-resistant prostate cancer.

Lipids are known to influence tumour growth, inflammation and chemoresistance. However, the association of circulating lipids with the clinical outcome of metastatic castration-resistant prostate cancer (CRPC) is unknown. We investigated associations between the plasma lipidome and clinical outcome in CRPC. Lipidomic profiling by liquid chromatography-tandem mass spectrometry was performed on plasma samples from a Phase 1 discovery cohort of 96 CRPC patients. Results were validated in an independent Phase 2 cohort of 63 CRPC patients. Unsupervised analysis of lipidomic profiles (323 lipid species) classified the Phase 1 cohort into two patient subgroups with significant survival differences (HR 2.31, 95% CI 1.44-3.68, p = 0.0005). The levels of 46 lipids were individually prognostic and were predominantly sphingolipids with higher levels associated with poor prognosis. A prognostic three-lipid signature was derived (ceramide d18:1/24:1, sphingomyelin d18:2/16:0, phosphatidylcholine 16:0/16:0) and was also associated with shorter survival in the Phase 2 cohort (HR 4.8, 95% CI 2.06-11.1, p = 0.0003). The signature was an independent prognostic factor when modelled with clinicopathological factors or metabolic characteristics. The association of plasma lipids with CRPC prognosis suggests a possible role of these lipids in disease progression. Further research is required to determine if therapeutic modulation of the levels of these lipids by targeting their metabolic pathways may improve patient outcome.

Phase 2 study of circulating microRNA biomarkers in castration-resistant prostate cancer.

BACKGROUND: Biomarkers of therapeutic response and prognosis are needed to assist in the sequencing of treatments for metastatic castration-resistant prostate cancer (CRPC). Previously in a Phase 1 discovery study, we identified 14 circulating microRNAs that were associated with response to docetaxel chemotherapy or overall survival. We performed a Phase 2 validation study to verify these findings. METHODS: Using real-time PCR, the levels of the 14 microRNAs were measured in plasma collected before and after the first cycle of docetaxel from a Phase 2 cohort of 89 patients. RESULTS: The microRNAs were not associated with docetaxel response in the Phase 2 cohort. Higher baseline levels of six microRNAs, predominantly of the miR-200 family, were confirmed to be associated with shorter overall survival. A microRNA signature comprising these six microRNAs predicted high-risk patients in the Phase 2 cohort with a hazard ratio of 4.12 (95% CI 2.20-7.70, P=0.000001). The signature was an independent predictor in multivariable analysis with clinicopathological factors. CONCLUSIONS: The association of circulating microRNAs with overall survival suggests their involvement in CRPC progression.

Predictive value of the 2014 International Society of Urological Pathology grading system for prostate cancer in patients undergoing radical prostatectomy with long-term follow-up.

OBJECTIVE: To assess the relationship between the International Society of Urological Pathology (ISUP) 2014 grading system, biochemical recurrence (BCR) and clinical recurrence (CLR) after radical prostatectomy (RP), to determine whether the 2014 ISUP grading system is a better predictor of survival compared with the previous Gleason scoring systems, and to investigate whether incorporation of the tertiary pattern/grade into the ISUP scoring system significantly improves its efficacy. PATIENTS AND METHODS: A total of 635 RP cases (1991-1999) were identified from a database at a single institution. A histopathology review was performed to re-grade the cases as per the ISUP 2014 grading system. All relevant clinicopathological data and clinical follow-up (median [range] 15.25 [0.3-26] years) were obtained. Log-rank, Kaplan-Meier, Cox regression and Harrell's concordance c-indices analyses were performed. RESULTS: At a median follow-up of 15 years, 276 patients (44%) had BCR and 41 (7%) had CLR. Grade Groups 1, 2, 3, 4 and 5 were seen in 112 (18%), 307 (48%), 129 (20%), 33 (5%) and 54 patients (9%), respectively: 337 (53%) were upgraded, while 70 (11%) were downgraded compared with the 1992 Gleason system. Grade Group (hazard ratio [HR] 4.9; P < 0.001) and preoperative prostate-specific antigen (PSA) level (HR 1.4; P < 0.001) were independent predictors of BCR. Only Grade Group 5 (HR 12.3; P = 0.02), preoperative PSA (HR 1.6; P < 0.001), stage pT3b (HR 3.1; P = 0.03) and pT4 (HR 12.4; P < 0.001) independently predicted CLR. Harrell's c-indices showed that the 2014 ISUP grading system was a significantly better predictor of BCR and CLR as well as prostate cancer-specific death, compared with the 2005 ISUP modified Gleason system. The replacement of the secondary pattern by the tertiary pattern did not alter the prognostic efficacy of the ISUP 2014 grading system. CONCLUSIONS: The ISUP 2014 grading system is a significant independent predictor of both BCR and CLR, outperforming the 2005 ISUP modified Gleason system. This classification system has the potential to influence clinical decision-making after RP.

Loss of AZGP1 as a Superior Predictor of Relapse in Margin-Positive Localized Prostate Cancer.

BACKGROUND: Positive surgical margins (PSMs) in localized prostate cancer (PC) confer a two- to three-fold increased risk of biochemical relapse (BR). Absent/weak AZGP1 expression and Gleason grade ≥4 at the margin are each independent predictors of BR in patients with PSMs. Our study aimed to determine whether the biomarkers AZGP1 expression and Gleason grade at the site of a PSM are significant independent markers of biochemical and clinical relapse (CR) when modeled together and whether one of these biomarkers may be superior in its capacity to predict outcome. METHODS: A cohort of 275 consecutive patients with margin-positive localized PC following surgery were assessed for Gleason grade and AZGP1 expression at the PSM. BR-free survival was the primary end-point, while CR-free survival and PC-specific death were secondary endpoints. Kaplan-Meier Analysis and Cox Proportional Hazards Modeling were performed. RESULTS: Absent AZGP1 expression was significantly associated with increased risk of BR (P = 0.001) and PC-specific death (P = 0.02). Gleason grade ≥4 at PSM was associated with BR (P = 0.02), CR (P = 0.003), and PC-specific death (P = 0.004). On multivariable analysis, absent AZGP1 expression remained an independent predictor of BR (HR 2.4, 95%CI 1.5-3.9, P < 0.001) when modeled with Gleason grade at margin (HR 1.3, 95%CI 0.9-1.9, P = 0.16), preoperative PSA (P = 0.002), seminal vesicle involvement (P = 0.002), extraprostatic extension (P = 0.001), Gleason score (P = 0.01), adjuvant treatment (P = 0.75), linear length of the involved margin (P = 0.001) and margin number (P = 0.09). CONCLUSION: Absent AZGP1 expression is an independent predictor of BR in margin-positive localized PC and is associated with increased PC-specific mortality in a Phase II study. Absent AZGP1 expression was superior to Gleason grade at PSM in predicting relapse and should be incorporated into subsequent clinical trials of post-operative radiotherapy in men with margin-positive PC. Prostate 76:1491-1500, 2016. © 2016 Wiley Periodicals, Inc.

PCPro: a clinically accessible, circulating lipid biomarker signature for poor-prognosis metastatic prostate cancer.

BACKGROUND: Using comprehensive plasma lipidomic profiling from men with metastatic castration-resistant prostate cancer (mCRPC), we have previously identified a poor-prognostic lipid profile associated with shorter overall survival (OS). In order to translate this biomarker into the clinic, these men must be identifiable via a clinically accessible, regulatory-compliant assay. METHODS: A single regulatory-compliant liquid chromatography-mass spectrometry assay of candidate lipids was developed and tested on a mCRPC Discovery cohort of 105 men. Various risk-score Cox regression prognostic models of OS were built using the Discovery cohort. The model with the highest concordance index (PCPro) was chosen for validation and tested on an independent Validation cohort of 183 men. RESULTS: PCPro, the lipid biomarker, contains Cer(d18:1/18:0), Cer(d18:1/24:0), Cer(d18:1/24:1), triglycerides and total cholesterol. Within the Discovery and Validation cohorts, men who were PCPro positive had significantly shorter OS compared to those who were PCPro negative (Discovery: median OS 12.0 months vs 24.2 months, hazard ratio (HR) 3.75 [95% confidence interval (CI) 2.29-6.15], p < 0.001, Validation: median OS 13.0 months vs 25.7 months, HR = 2.13 [95% CI 1.46-3.12], p < 0.001). CONCLUSIONS: We have developed PCPro, a lipid biomarker assay capable of prospectively identifying men with mCRPC with a poor prognosis. Prospective clinical trials are required to determine if men who are PCPro positive will benefit from therapeutic agents targeting lipid metabolism.

Plasma Lipidomic Profiling Identifies Elevated Triglycerides as Potential Risk Factor in Chemotherapy-Induced Peripheral Neuropathy.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of cytotoxic cancer treatment, often necessitating dose reduction (DR) or chemotherapy discontinuation (CD). Studies on peripheral neuropathy related to chemotherapy, obesity, and diabetes have implicated lipid metabolism. This study examined the association between circulating lipids and CIPN. METHODS: Lipidomic analysis was performed on plasma samples from 137 patients receiving taxane-based treatment. CIPN was graded using Total Neuropathy Score-clinical version (TNSc) and patient-reported outcome measure European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-CIPN (EORTC-QLQ-CIPN20). RESULTS: A significant proportion of elevated baseline lipids were associated with high-grade CIPN defined by TNSc and EORTC-QLQ-CIPN20 including triacylglycerols (TGs). Multivariable Cox regression on lipid species, adjusting for BMI, age, and diabetes, showed several elevated baseline TG associated with shorter time to DR/CD. Latent class analysis identified two baseline lipid profiles with differences in risk of CIPN (hazard ratio, 2.80 [95% CI, 1.50 to 5.23]; P = .0013). The higher risk lipid profile had several elevated TG species and was independently associated with DR/CD when modeled with other clinical factors (diabetes, age, BMI, or prior numbness/tingling). CONCLUSION: Elevated baseline plasma TG is associated with an increased risk of CIPN development and warrants further validation in other cohorts. Ultimately, this may enable therapeutic intervention.

BRCA-deficient metastatic prostate cancer has an adverse prognosis and distinct genomic phenotype.

BACKGROUND: Genomic alterations in DNA damage response (DDR) genes are common in metastatic castration-resistant prostate cancer (mCRPC). Understanding how these genomic events impact prognosis and/or treatment response is vital for optimising clinical outcomes. METHODS: Targeted sequencing was performed on 407 plasma samples from 375 men with mCRPC. Using the CLIA-certified PredicineCARE™ cell-free DNA (cfDNA) assay, pathogenic alterations in 152 key genes (including 27 DDR-related genes) were assessed, as was the presence and mechanisms of biallelic loss in BRCA2. FINDINGS: At least one DDR alteration was present in 34.5% (129/375) of patients (including monoallelic alterations). The most frequently altered DDR genes were BRCA2 (19%), ATM (13%), FANCA (5%), CHEK2 (5%) and BRCA1 (3%). Patients with BRCA alterations, especially BRCA2, had significantly worse progression-free survival (PFS) (Hazard ratio (HR) 3.3 [95% CI 1.9-6.0]; Cox regression p < 0.001), overall survival (HR 2.2 [95% CI 1.1-4.5]; Cox regression p = 0.02) and PSA response rates to androgen receptor (AR) pathway inhibitors (32% vs 60%, chi-square p = 0.02). BRCA-deficient tumours were also enriched for alterations within multiple genes including in the AR and PI3K pathways. Zygosity of BRCA2 alterations had no discernible impact on clinical outcomes, with similarly poor PFS for monoallelic vs biallelic loss (median 3.9 months vs 3.4 months vs copy neutral 9.8 months). INTERPRETATION: These data emphasise that the BRCA genes, in particular BRCA2, are key prognostic biomarkers in mCRPC. The clinical utility of BRCA2 as a marker of poor outcomes may, at least in cfDNA assays, be independent of the zygosity state detected. Enrichment of actionable genomic alterations in cfDNA from BRCA-deficient mCRPC may support rational co-targeting strategies in future clinical trials. FUNDING: Several funding sources have supported this study. A full list is provided in the Acknowledgments. No funding was received from Predicine, Inc. during the conduct of the study.

From Research to the Real World: Moving Prostate Cancer Biomarkers into the Clinic.

Effective biomarkers provide the potential to significantly improve treatment decisions and outcomes in prostate cancer patients. While the literature is inundated with prostate cancer biomarkers in the early phases of testing, very few reach the clinic. Research should be focused on progressing effective biomarkers from discovery to clinical utility and implementation. Presented here is an overview of the biomarker development pathway and a discussion of the current issues impeding our efforts to deliver biomarkers that improve clinical outcomes in men with prostate cancer.

Review of systemic chemotherapy in unresectable colorectal peritoneal carcinomatosis.

Colorectal cancer remains the third most common malignancy in Australia with the peritoneum being the second most common metastatic site. Colorectal peritoneal carcinomatosis (CPC) can be treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy but this is only limited to a small subset of patients. Those with inoperable disease have a particularly poor prognosis. While the ideal systemic regimen has not been defined, 5-fluorouracil-based chemotherapy regimens appear to provide overall and progression free survival benefits. The role of targeted agents such as bevacizumab (vascular endothelial growth factor inhibitor) or cetuximab (epidermal growth factor inhibitor) in the setting of CPC is still evolving. Currently, retrospective analyses have shown promising results for the use of bevacizumab in addition to systemic chemotherapy but similar results have not been seen with cetuximab or panitumumab. However, there is significant heterogeneity in the trial data, lack of prospective randomized controlled trials and demonstrated treatment variability based on age and tumour characteristics. This review summarises the current literature in regard to treatment in the unresectable CPC setting as well as discussing issues with the current data and highlighting the need for further trials.

The role of chemotherapy in the treatment of advanced appendiceal cancers: summary of the literature and future directions.

Appendiceal cancer is rare and encompasses a diverse group of tumours ranging from low-grade appendiceal mucinous neoplasms to high-grade adenocarcinomas. Appendiceal cancers often spread to the peritoneal cavity causing extensive mucinous dissemination and peritoneal metastases. Prognosis varies with histological subtype. Cytoreductive surgery and heated intraperitoneal chemotherapy is well-established as the most effective treatment achieving long-term survival in some patients. Chemotherapy regimens used to treat appendiceal cancer are extrapolated from the colorectal cancer setting, but disease biology differs and outcomes are inferior. The role of chemotherapy in the treatment of appendiceal cancer remains poorly defined. There is an urgent need to develop novel tailored treatment strategies in the perioperative and unresectable setting. This review aims to evaluate the literature for patients who received intraperitoneal and systemic chemotherapy for appendiceal cancers.

GUIDE: a randomised non-comparative phase II trial of biomarker-driven intermittent docetaxel versus standard-of-care docetaxel in metastatic castration-resistant prostate cancer (clinical trial protocol).

Objective: To determine the efficacy and safety of intermittent docetaxel chemotherapy guided by circulating methylated glutathione S-transferase Pi-1 (mGSTP1) in men with metastatic castration-resistant prostate cancer (CRPC). Patients and Methods: GUIDE (NCT04918810) is a randomised, two-arm, non-comparative phase-2 trial recruiting 120 patients at six Australian centres. Patients with Prostate Cancer Working Group-3 defined metastatic CRPC who are commencing docetaxel 75 mg/m2 q3w will be pre-screened for detectable mGSTP1 at baseline ± following two cycles of treatment. Those with detectable plasma mGSTP1 at baseline that becomes undetectable after two cycles of chemotherapy will be eligible for GUIDE. Prior to Cycle 4 of docetaxel, these patients are randomised 2:1 to one of two treatment arms: Arm A (cease docetaxel and reinstitute if mGSTP1 becomes detectable) or Arm B (continue docetaxel 75 mg/m2 q3w in accordance with clinician's usual practice). The primary endpoint is radiographic progression-free survival. Secondary endpoints include time on treatment holidays, safety, patient-reported outcomes, overall survival, health resource use, and cost associated with treatment. Enrolment commenced November 2021. Results and Conclusion: The results of this trial will generate data on the clinical utility of mGSTP1 as a novel biomarker to guide treatment de-escalation in metastatic CRPC.

Modulation of Plasma Lipidomic Profiles in Metastatic Castration-Resistant Prostate Cancer by Simvastatin.

Elevated circulating sphingolipids are associated with shorter overall survival and therapeutic resistance in metastatic castration-resistant prostate cancer (mCRPC), suggesting that perturbations in sphingolipid metabolism promotes prostate cancer growth. This study assessed whether addition of simvastatin to standard treatment for mCRPC can modify a poor prognostic circulating lipidomic profile represented by a validated 3-lipid signature (3LS). Men with mCRPC (n = 27) who were not on a lipid-lowering agent, were given simvastatin for 12 weeks (40 mg orally, once daily) with commencement of standard treatment. Lipidomic profiling was performed on their plasma sampled at baseline and after 12 weeks of treatment. Only 11 men had the poor prognostic 3LS at baseline, of whom five (45%) did not retain the 3LS after simvastatin treatment (expected conversion rate with standard treatment = 19%). At baseline, the plasma profiles of men with the 3LS displayed higher levels (p < 0.05) of sphingolipids (ceramides, hexosylceramides and sphingomyelins) than those of men without the 3LS. These plasma sphingolipids were reduced after statin treatment in men who lost the 3LS (mean decrease: 23−52%, p < 0.05), but not in men with persistent 3LS, and were independent of changes to plasma cholesterol, LDL-C or triacylglycerol. In conclusion, simvastatin in addition to standard treatment can modify the poor prognostic circulating lipidomic profile in mCRPC into a more favourable profile at twice the expected conversion rate.

When ordinary days become extraordinary: the response to H1N1 at the Izaak Walton Killam Health Centre.

In April 2009, the H1N1 swine flu virus entered Canada with a sentinel case presenting in a private school in Windsor, Nova Scotia, signaling the beginning of wave 1 of a pandemic. By June, the World Health Organization raised the alert level to 6. Wave 2 was expected in 4 to 6 months. Between waves, the IWK took the opportunity to revise pandemic plans that had been prepared for the H5N1 avian influenza virus to ensure that the organization would be prepared for the emergency response that would be required to manage large numbers of ill people seeking healthcare services for the pending second wave of the swine flu.

Mainstream consent programs for genetic counseling in cancer patients: A systematic review.

As demand for germline genetic testing for cancer patients increases, novel methods of genetic counseling are required. One such method is the mainstream consent pathway, whereby a member of the oncology team (rather than a genetic specialist) is responsible for counseling, consenting, and arranging genetic testing for cancer patients. We systematically reviewed the literature for evidence evaluating mainstream pathways for patients with breast, ovarian, colorectal, and prostate cancer. Medline, EMBASE, and Cochrane Library were searched for studies that met inclusion and exclusion criteria. Article references were checked for additional studies. Trial databases were searched for ongoing studies. Of the 13 papers that met inclusion criteria, 11 individual study groups were identified (two study groups had two publications each). Ten of the 11 studies evaluated the acceptability, feasibility, and impact of BRCA testing for patients and/or clinicians in different clinical settings in breast and ovarian cancer, while the final study explored the attitudes of colorectal specialists toward genetic testing for colorectal cancer. None involved prostate cancer. Overall, mainstream pathways were acceptable and feasible. Medical oncologist- and nurse-driven pathways were particularly successful, with both patients and clinicians satisfied with this process. Although the content of pretest counseling was less consistent compared with counseling via the traditional model, patients were largely satisfied with the education they received. Further research is required to evaluate the mainstream pathway for men with prostate cancer.

Patient satisfaction with telehealth consultations in medical oncology clinics: A cross-sectional study at a metropolitan centre during the COVID-19 pandemic.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has resulted in a widespread adoption of telehealth (phone and video consultations) in cancer care worldwide. The aim of this study was to determine patient satisfaction with telehealth consultations with their medical oncologist at a tertiary cancer centre in Sydney, Australia. METHODS: Patients who attended a routine telehealth appointment at the medical oncology outpatient clinic were recruited to complete a questionnaire containing 16 items, each on a 5-point Likert scale regarding satisfaction levels in various aspects of telehealth and their willingness to continue telehealth after the pandemic. Patients were also invited to provide suggestions for improvement. RESULTS: In total, 150 patients were invited to participate, and 103 valid questionnaires were returned. Median age was 63 years (range: 25-90), 49% of patients were male, 63% of patients had advanced cancer and 81% were on active treatment. In total, 95% of participants indicated that they were satisfied (score ≥4) with telehealth. 82% of participants preferred to continue telehealth consultations after the coronavirus disease 2019 pandemic, but ideally with a mix of telehealth and in-person consultations. Phone appointments (vs. video, p < 0.002), patients with advanced cancer (vs. early, p < 0.036) and pre-chemotherapy/immunotherapy/targeted therapy treatment reviews (vs. follow-up appointments, p < 0.001) were significantly associated with a willingness to continue telehealth. DISCUSSION: Patients were overwhelmingly satisfied with telehealth during the study period and were willing to continue telehealth for some appointments beyond the coronavirus disease 2019 pandemic. More research into the effectiveness, safety and implementation of telehealth to compliment traditional face-to-face services for patient-centred cancer care is required.

Evaluation of a Mainstream Model of Genetic Testing for Men With Prostate Cancer.

PURPOSE: To identify the approximately 12% with inherited cancer predisposition, all men with metastatic prostate cancer (mPC) should be offered germline genetic testing. This guides treatment choices and impacts cancer prevention in the family. Limited genetic services globally present a barrier to testing. This study tested a potential solution, "mainstreaming," where counseling and testing are performed by the patient's oncologist. PATIENTS AND METHODS: Men with mPC at three Australian sites were offered germline genetic testing at their medical oncology appointment. Panel testing (ATM, BRCA1, BRCA2, BRIP1, CHEK2, EPCAM, FANCA, HOXB13, MLH1, MSH2, MSH6, NBN, PALB2, PMS2, RAD51D, and TP53) was performed on saliva/blood (Invitae, San Francisco, CA). Primary outcomes were clinician and patient satisfaction. Secondary outcomes included mutation rates and resource allocation. RESULTS: Of 66 men offered testing, 63 (95%) accepted. Four pathogenic variants were identified (two BRCA2, one NBN, and one MSH6). Fifty patients and nine clinicians completed questionnaires. Satisfaction was high. All patients were pleased to have had testing overall, 98% (46 of 47) to have had testing at their usual oncology appointment, and all to receive results from their usual specialist, rather than a separate genetics appointment. A total of 88% (7 of 8) of clinicians felt confident, and all were satisfied with mainstreaming. Mainstreaming was resource efficient, requiring 87% fewer genetic consultations than traditional genetic counseling. CONCLUSION: This study demonstrates that mainstreaming of men with mPC is feasible, resource efficient, and satisfactory for clinicians and patients. Widespread implementation as standard of care would facilitate timely access to genetic testing for men with mPC.