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Introduction: Unresectable and metastatic small cell carcinoma of the prostate (SCPC) is a rare and aggressive disease that is under-represented in clinical trials. We carried out a retrospective chart review of metastatic or unresectable SCPC patients at British Columbia (BC) Cancer centers, studying diagnosis and treatment patterns., Methods: Drug-dispensing records from the six BC Cancer centers were obtained from 2002-2017. For each patient, information was collected on baseline information prior to therapy and for each line of treatment. Treatments at each line were compared regarding time to progression and overall survival by Kaplan-Meier curves., Results: Forty-one patients received treatment; 65.6% had metastatic disease and 61% had pure small cell carcinoma. Median time from treatment to death was 10 months (95% confidence interval [CI] 6-16). Patients with initially prostate-confined disease had a better median overall survival (mOS) of 21 months (95% CI 13-34) compared to those with initially locally advanced (mOS 19 months, 95% CI 5-37) and metastatic disease (mOS 8 months, 95% CI 6-10) (log-rank p=0.0364). All patients received either cisplatin- or carboplatin-based combination chemotherapy as the first-line treatment and 36.7% received second-line therapy. Time to second-line therapy was eight months for those who presented with metastatic SCPC, compared to 13 months for those with initial non-metastatic SCPC., Conclusions: This single-province, multi-institution cohort reports data on unresectable and metastatic SCPC and highlights the poor prognosis of this rare disease entity.

Purpose: Exercise has been underutilized in people with advanced or incurable cancer despite the potential to improve physical function and reduce psychosocial morbidity, especially for people with bone metastases because of concerns over skeletal complications. The International Bone Metastases Exercise Working Group (IBMEWG) was formed to develop best practice recommendations for exercise programming for people with bone metastases on the basis of published research, clinical experience, and expert opinion., Methods: The IBMEWG undertook sequential steps to inform the recommendations: (1) modified Delphi survey , (2) systematic review , (3) cross-sectional survey to physicians and nurse practitioners, (4) in-person meeting of IBMEWG to review evidence from steps 1-3 to develop draft recommendations, and (5) stakeholder engagement ., Results: Recommendations emerged from the contributing evidence and IBMEWG discussion for pre-exercise screening, exercise testing, exercise prescription, and monitoring of exercise response. Identification of individuals who are potentially at higher risk of exercise-related skeletal complication is a complex interplay of these factors: (1) lesion-related, (2) cancer and cancer treatment-related, and (3) the person-related. Exercise assessment and prescription requires consideration of the location and presentation of bone lesion(s) and should be delivered by qualified exercise professionals with oncology education and exercise prescription experience. Emphasis on postural alignment, controlled movement, and proper technique is essential., Conclusion: Ultimately, the perceived risk of skeletal complications should be weighed against potential health benefits on the basis of consultation between the person, health care team, and exercise professionals. These recommendations provide an initial framework to improve the integration of exercise programming into clinical care for people with bone metastases., Competing Interests: Kristin L. CampbellHonoraria: Astellas Pharma Prue CormieStock and Other Ownership Interests: Exercise Oncology EDU Pty LtdOther Relationship: EX-MED Cancer Ltd Sarah WellerResearch Funding: Astellas Pharma Shabbir M. H. AlibhaiStock and Other Ownership Interests: ResMedHonoraria: Astellas Scientific and Medical Affairs Inc Kate A. BolamStock and Other Ownership Interests: Novo Nordisk Celestia S. HiganoEmployment: CTI BioPharma Corp (I)Stock and Other Ownership Interests: CTI BioPharma Corp (I)Honoraria: Astellas PharmaConsulting or Advisory Role: Bayer, Ferring, Clovis Oncology, Blue Earth Diagnostics, Janssen, Hinova Pharmaceuticals, Pfizer, AstraZeneca, Carrick Therapeutics, Novartis, Merck Sharp & Dohme, Astellas Pharma, Myovant Sciences, Genentech, MenariniResearch Funding: Aragon Pharmaceuticals (Inst), AstraZeneca (Inst), Medivation (Inst), Emergent BioSolutions (Inst), Bayer (Inst), Pfizer (Inst), Roche (Inst), Astellas Pharma (Inst), Clovis Oncology (Inst), Ferring (Inst), eFFECTOR Therapeutics (Inst)Travel, Accommodations, Expenses: Pfizer, Janssen Oncology, Novartis, Merck Sharp & Dohme, Carrick Therapeutics Kirstin LaneStock and Other Ownership Interests: Moderna TherapeuticsTravel, Accommodations, Expenses: Astellas Pharma Robert U. NewtonHonoraria: GenesisCareResearch Funding: IpsenTravel, Accommodations, Expenses: Genesis Cancer Care Morten QuistEmployment: Zealand Pharmaceuticals (I)Honoraria: AstraZeneca Jennifer RauwHonoraria: AstraZenecaSpeakers' Bureau: GlaxoSmithKlineTravel, Accommodations, Expenses: AstraZeneca Friederike RosenbergerStock and Other Ownership Interests: BioNTech, Bristol Myers Squibb, AstraZenecaHonoraria: Bristol Myers Squibb, Hexal Kathryn H. SchmitzPatents, Royalties, Other Intellectual Property: Fees from the educational program I developed that are now offered through Klose Training and Consulting Joachim WiskemannHonoraria: Pfizer, Lilly, Novartis Jennifer GoulartResearch Funding: Astellas Pharma (Inst)No other potential conflicts of interest were reported.

Purpose: This study investigated therapeutic potential of integrated genome and transcriptome profiling of metastatic sarcoma, a rare but extremely heterogeneous group of aggressive mesenchymal malignancies with few systemic therapeutic options., Methods: Forty-three adult patients with advanced or metastatic non-GI stromal tumor sarcomas of various histology subtypes who were enrolled in the Personalized OncoGenomics program at BC Cancer were included in this study. Fresh tumor tissues along with blood samples underwent whole-genome and transcriptome sequencing., Results: The most frequent genomic alterations in this cohort are large-scale structural variation and somatic copy number variation. Outlier RNA expression as well as somatic copy number variations, structural variations, and small mutations together suggest the presence of one or more potential therapeutic targets in the majority of patients in our cohort. Point mutations or deletions in known targetable cancer genes are rare; for example, tuberous sclerosis complex 2 provides a rationale for targeting the mammalian target of rapamycin pathway, resulting in a few patients with exceptional clinical benefit from everolimus. In addition, we observed recurrent 17p11-12 amplifications, which seem to be a sarcoma-specific event. This may suggest that this region harbors an oncogene(s) that is significant for sarcoma tumorigenesis. Furthermore, some sarcoma tumors carrying a distinct mutational signature suggestive of homologous recombination deficiency seem to demonstrate sensitivity to double-strand DNA-damaging agents., Conclusion: Integrated large-scale genomic analysis may provide insights into potential therapeutic targets as well as novel biologic features of metastatic sarcomas that could fuel future experimental and clinical research and help design biomarker-driven basket clinical trials for novel therapeutic strategies.

Background: Gestational choriocarcinoma is a rare malignancy believed to arise from the trophoblast cells of the placenta. Despite the frequently aggressive clinical nature, choriocarcinoma has been routinely curable with cytotoxic chemotherapy for over 50 years. To date little is known regarding the route to oncogenesis in this malignancy., Methods: In a case of intraplacental choriocarcinoma, we have performed detailed genetic studies including microsatellite analysis, whole genome sequencing (WGS) and methylation analysis of the tumour and surrounding mature placenta., Results: The results of the WGS sequencing indicated a very low level of mutation and the absence of any driver mutations or oncogene activity in the tumour. The methylation analysis identified a distinctly different profile in the tumour from that of the mature placenta. Comparison with a panel of reference methylation profiles from different stages of placental development indicated that the tumour segregated with the first trimester samples., Conclusions: These findings suggest that gestational choriocarcinoma is likely to arise as a result of aberrations of methylation during development, rather than from DNA mutations. The results support the hypothesis that gestational choriocarcinoma arises from a normally transient early trophoblast cell. At this point in development this cell naturally has a phenotype of rapid division, tissue invasion and sensitivity to DNA damaging chemotherapy that is very similar to that of the mature choriocarcinoma cell.