Project description:In Japan, comprehensive genomic profiling (CGP) tests for refractory cancer patients have been approved since June 2019, under the requirement that all cases undergoing CGP tests are annotated by the molecular tumor board (MTB) at each government-designated hospital. To investigate improvement in precision oncology, we evaluated and compared the proportion of cases receiving matched treatments according to CGP results and those recommended to receive genetic counseling at all core hospitals between the first period (11 hospitals, June 2019 to January 2020) and second period (12 hospitals, February 2020 to January 2021). A total of 754 and 2294 cases underwent CGP tests at core hospitals in the first and second periods, respectively; 28 (3.7%) and 176 (7.7%) patients received matched treatments (p < 0.001). Additionally, 25 (3.3%) and 237 (10.3%) cases were recommended to receive genetic counseling in the first and second periods, respectively (p < 0.001). The proportion was associated with the type of CGP test: tumor-only (N = 2391) vs. tumor-normal paired (N = 657) analysis (10.0% vs. 3.5%). These results suggest that recommendations regarding available clinical trials in networked MTBs might contribute to increasing the numbers of matched treatments, and that tumor-normal paired rather than tumor-only tests can increase the efficiency of patient referrals for genetic counseling.
Project description:Aim: To describe patient communication challenges encountered by oncology clinicians, which represent a fundamental barrier to implementing precision oncology. Materials & methods: We conducted three focus groups including breast, melanoma and thoracic oncology clinicians regarding their precision oncology communication experiences. Transcripts were reviewed and coded using inductive thematic text analysis. Results: We identified four themes: varied definitions of precision oncology exist, clinicians and patients face unique challenges to precision oncology implementation, patient communication challenges engendered or heightened by precision oncology implementation and clinician communication solutions and training needs. Conclusion: This study elucidated clinicians' perspectives on implementing precision oncology and related communication challenges. Understanding these challenges and developing strategies to help clinicians navigate these discussions are critical for ensuring that patients reap the full benefits of precision oncology.
Project description:BackgroundPrecision oncology relies on molecular diagnostics, and the value-proposition of modern healthcare networks promises a higher standard of care across partner sites. We present the results of a clinical pilot to standardize precision oncology workflows.MethodsWorkflows are defined as the development, roll-out, and updating of disease-specific molecular order sets. We tracked the timeline, composition, and effort of consensus meetings to define the combination of molecular tests. To assess clinical impact, we examined order set adoption over a two-year period (before and after roll-out) across all gastrointestinal and hepatopancreatobiliary (GI) malignancies, and by provider location within the network.ResultsDevelopment of 12 disease center-specific order sets took ~9 months, and the average number of tests per indication changed from 2.9 to 2.8 (P = .74). After roll-out, we identified significant increases in requests for GI patients (17%; P < .001), compliance with testing recommendations (9%; P < .001), and the fraction of "abnormal" results (6%; P < .001). Of 1088 GI patients, only 3 received targeted agents based on findings derived from non-recommended orders (1 before and 2 after roll-out); indicating that our practice did not negatively affect patient treatments. Preliminary analysis showed 99% compliance by providers in network sites, confirming the adoption of the order sets across the network.ConclusionOur study details the effort of establishing precision oncology workflows, the adoption pattern, and the absence of harm from the reduction of non-recommended orders. Establishing a modifiable communication tool for molecular testing is an essential component to optimize patient care via precision oncology.
Project description:Precision oncology, where patients are given therapies based on their genomic profile and disease trajectory, is rapidly evolving to become a pivotal part of cancer management, supported by regulatory approvals of biomarker-matched targeted therapies and cancer immunotherapies. However, next-generation sequencing (NGS)-based technologies have revealed an increasing number of molecular-based cancer subtypes with rare patient populations, leading to difficulties in executing/recruiting for traditional clinical trials. Therefore, approval of novel therapeutics based on traditional interventional studies may be difficult and time consuming, with delayed access to innovative therapies. Real-world data (RWD) that describe the patient journey in routine clinical practice can help elucidate the clinical utility of NGS-based genomic profiling, multidisciplinary case discussions, and targeted therapies. We describe key learnings from the setup of WAYFIND-R (NCT04529122), a first-of-its-kind global cancer registry collecting RWD from patients with solid tumors who have undergone NGS-based genomic profiling. The meaning of 'generalizability' and 'high quality' for RWD across different geographic areas was revisited, together with patient recruitment processes, and data sharing and privacy. Inspired by these learnings, WAYFIND-R's design will help physicians discuss patient treatment plans with their colleagues, improve understanding of the impact of treatment decisions/cancer care processes on patient outcomes, and provide a platform to support the design and conduct of further clinical/epidemiologic research. WAYFIND-R demonstrates user-friendly, electronic case report forms, standardized collection of molecular tumor board-based decisions, and a dashboard providing investigators with access to local cohort-level data and the ability to interact with colleagues or search the entire registry to find rare populations. Overall, WAYFIND-R will inform on best practice for NGS-based treatment decisions by clinicians, foster global collaborations between cancer centers and enable robust conclusions regarding outcome data to be drawn, improve understanding of disparities in patients' access to advanced diagnostics and therapies, and ultimately drive advances in precision oncology.
Project description:We introduce OncoLoop, a highly-generalizable, precision medicine framework to triangulate between available mouse models, human tumors, and large-scale drug perturbational assays with in vivo validation to predict personalized treatment
Project description:Over the last few decades, molecularly targeted agents have been used for the treatment of metastatic colorectal cancer. They have made remarkable contributions to prolonging the lives of patients. The emergence of several biomarkers and their introduction to the clinic have also aided in guiding such treatment. Recently, next-generation sequencing (NGS) has enabled clinicians to identify these biomarkers more easily and reliably. However, there is considerable uncertainty in interpreting and implementing the vast amount of information from NGS. The clinical relevance of biomarkers other than NGS are also subjects of debate. This review covers controversial issues and recent findings on such therapeutics and their molecular targets, including VEGF, EGFR, BRAF, HER2, RAS, actionable fusions, Wnt pathway and microsatellite instability for comprehensive understanding of obstacles on the road to precision oncology in metastatic colorectal cancer.
Project description:The advent of molecular diagnostics and the rising number of targeted therapies have facilitated development of precision oncology for cancer patients. In order to demonstrate its impact for patients with metastatic breast cancer (mBC), we initiated a Molecular Tumor Board (MTB) to provide treatment recommendations for mBC patients who had disease progression under standard treatment. NGS (next generation sequencing) was carried out using the Oncomine multi-gene panel testing system (Ion Torrent). The MTB reviewed molecular diagnostics' results, relevant tumor characteristics, patient's course of disease and made personalized treatment and/or diagnostic recommendations for each patient. From May 2017 to December 2019, 100 mBC patients were discussed by the local MTB. A total 72% of the mBC tumors had at least one molecular alteration (median 2 per case, range: 1 to 6). The most frequent genetic changes were found in the following genes: PIK3CA (19%) and TP53 (17%). The MTB rated 53% of these alterations as actionable and treatment recommendations were made accordingly for 49 (49%) patients. Sixteen patients (16%) underwent the suggested therapy. Nine out of sixteen patients (56%; 9% of all) experienced a clinical benefit with a progression-free survival ratio ≥ 1.3. Personalized targeted therapy recommendations resulting from MTB case discussions could provide substantial benefits for patients with mBC and should be implemented for all suitable patients.
Project description:Outcome in treatment of childhood cancers has improved dramatically since the 1970s. This success was largely achieved by the implementation of cooperative clinical research trial groups that standardized and developed treatment of childhood cancer. Nevertheless, outcome in certain types of malignancies is still unfavorable. Intensification of conventional chemotherapy and radiotherapy improved outcome only marginally at the cost of acute and long-term side effects. Hence, it is necessary to develop targeted therapy strategies.Here, we review the developments and perspectives in precision medicine in pediatric oncology with a special focus on targeted drug therapies like kinase inhibitors and inducers of apoptosis, the impact of cancer genome sequencing and immunotherapy.
Project description:Radiation therapy is a critical component in the curative management of many solid tumor types, and advances in radiation delivery techniques during the past decade have led to improved disease control and quality of life for patients. During the same period, remarkable advances have also been made in understanding the genomic landscape of tumors; however, treatment decisions in radiation oncology continue to depend primarily on clinical and histopathologic characteristics rather than on the genetic features of the tumor or the patient. With the development of novel genomic techniques and their increasing use in clinical practice, radiation oncology is uniquely positioned to leverage these advances to identify novel biomarkers that could inform radiation dose, field, and the use of concurrent systemic agents. Here, we summarize efforts to use genomic techniques to guide radiation decisions, and we highlight some of the current opportunities and challenges that exist in attempting to apply precision oncology principles in radiation oncology.
Project description:Precision oncology is a rapidly evolving concept that holds great promise in cancer treatment. However, a cancer complexity attributed to genomic and acquired tumour heterogeneity limits treatment effectiveness and increases toxicity. These limitations refer to both systemic therapies and radiotherapy, which are two mainstays of non-invasive cancer treatment. By understanding cancer heterogeneity and utilising advanced tools to personalise treatment strategies, precision oncology has the potential to revolutionise cancer care. In this article, we review the current status of precision oncology in solid tumours, specifically focusing on the impact of tumour heterogeneity and genomic patient features on systemic therapies and radiation. We also discuss the implementation of novel tools, such as next-generation sequencing and liquid biopsies, to overcome this problem.