Patient-centric trials for therapeutic development in precision oncology

An enhanced understanding of the molecular pathology of disease gained from genomic studies is facilitating the development of treatments that target discrete molecular subclasses of tumours. Considerable associated challenges include how to advance and implement targeted drug-development strategies. Precision medicine centres on delivering the most appropriate therapy to a patient on the basis of clinical and molecular features of their disease. The development of therapeutic agents that target molecular mechanisms is driving innovation in clinical-trial strategies. Although progress has been made, modifications to existing core paradigms in oncology drug development will be required to realize fully the promise of precision medicine

The management of women with ductal carcinoma in situ of the breast in Australia and New Zealand between 2007 and 2016

Background: The incidence of detected ductal carcinoma in situ (DCIS) continues to increase and now accounts for 14% of all breast cancer, and 20%–25% of screen-detected cases. Treatment trends of DCIS are important in order to inform the ongoing debate about possible overdiagnosis and overtreatment, but have not been investigated for over a decade in Australia and New Zealand. Against this background, we aimed to describe the temporal trends in management of DCIS in Australian and New Zealander women. Methods: Using the BreastSurgANZ Quality Audit (BQA) database, we conducted a descriptive study of the trends of management of DCIS in Australia and New Zealand from 2007 to 2016. We assessed the frequency of surgical treatments, adjuvant therapies, and axillary surgery conducted in women with pure DCIS. Results: There were 17 883 cases of pure DCIS in 2007–2016 in Australia and New Zealand recorded in the BQA database. The treatment patterns were consistent with no changes over time. The most common surgical treatment was breast-conserving surgery (66%), followed by mastectomy (37%), and 36% of women with DCIS received sentinel node biopsy (SNB). Conclusion: The clinical management of women diagnosed with DCIS in Australia and New Zealand, appears stable over time. A substantial proportion of women with DCIS receive SNB and this aspect of surgical care warrants further exploration to determine whether it represents appropriate care. These results, alongside the outcomes of the ongoing clinical trials on the management of DCIS, will help inform if any changes to best practice treatment are required.Sofia Omling, Nehmat Houssami, Kevin McGeechan, Sophia Zackrisson, Gemma Jacklyn, David Walters, Alexandra Barratt, and Rachel Farbe

Focal Therapy Eligibility Determined by Magnetic Resonance Imaging/Ultrasound Fusion Biopsy

PurposeWe assessed focal therapy eligibility in men who underwent multiparametric magnetic resonance imaging and targeted biopsy with correlation to whole mount histology after radical prostatectomy.Materials and methodsSubjects were selected from among the 454 men in whom targeted biopsy proven prostate cancer was derived from regions of interest on multiparametric magnetic resonance imaging from 2010 to 2016. Focal therapy eligibility was limited to a maximum Gleason score of 4 + 3 in regions of interest with or without other foci of low risk prostate cancer (Gleason score 3 + 3 and less than 4 mm). Men who did not meet NCCN® intermediate risk criteria were classified as ineligible for focal therapy. Of the 454 men 64 underwent radical prostatectomy and biopsy findings were compared to final pathology findings.ResultsOf the 454 men with a biopsy proven region of interest 175 (38.5%) were eligible for focal therapy. Fusion biopsy, which combined targeted and template biopsy, had 80.0% sensitivity (12 of 15 cases), 73.5% specificity (36 of 49) and 75.0% accuracy (48 of 64) for focal therapy eligibility. Targeted cores alone yielded 73.3% sensitivity (11 of 15 cases), 47.9% specificity (23 of 48) and 54.7% accuracy (35 of 64). Gleason score and extension across the midline differed in 4 and 9, respectively, of the 13 cases that showed discordant biopsy and whole mount histology.ConclusionsUsing intermediate risk eligibility criteria more than a third of men with a targeted biopsy proven lesion identified on multiparametric magnetic resonance imaging would have been eligible for focal therapy. Eligibility determined by fusion biopsy was concordant with whole mount histology in 75% of cases. Improved selection criteria are needed to reliably determine focal therapy eligibility