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Background: The complexity of delivering precision medicine to oncology patients has led to the creation of molecular tumourboards (MTBs) for patient selection and assessment of treatment options. New technologies like the liquid biopsy are augmenting available therapeutic opportunities. This report aims to analyse the experience of our MTB in the implementation of personalised medicine in a cancer network., Materials and Methods: Patients diagnosed with solid tumours progressing to standard treatments were referred to our Phase I unit. They underwent comprehensive next generation sequencing (NGS) of either tumour tissue or cell-free circulating tumour DNA (ctDNA) or both. The MTB expressed either a positive or negative opinion for the treatment of the patients with discovered druggable alterations inside a clinical trial, in an expanded access programme, with a compassionate use. Afterwards, discovered alterations were matched with OncoKB levels of evidence for the choice of alteration-specific treatments in order to compare MTB outcomes with a standardised set of recommendations., Results: NGS was performed either on ctDNA or tumour tissue or in both of them in 204 patients. The MTB evaluated 173 of these cases. Overall, the MTB proposed alteration-specific targeted therapy to 72 patients (41.6%). 49 patients (28.3% of the total evaluated) were indicated to enter a clinical trial. In 29 patients with matched liquid biopsy NGS (lbNGS), tumour tissue NGS (ttNGS) and MTB evaluation, the MTB changed the treatment strategy coming from standardised recommendations based on lbNGS and ttNGS alone in 10 patients (34.5%), thanks to the evaluation of other clinical parameters. In our cohort, lbNGS was more likely, compared with ttNGS, to detect point mutations (OR 11, 95% CI 2.9 to 24.1, p<0.001) and all-type alterations (OR 13.6, 95% CI 5.5 to 43.2, p<0.001) from the same genes of matched patients., Conclusions: Our MTB allows patients with refractory cancer to be included in clinical trials and improves the precision of clinical decisions compared with a standardised set of mutation-driven recommendations., Competing Interests: Competing interests: None declared.

Purpose: Case reports and small prospective trials suggest that administering targeted therapies to patients with advanced cancer and an identified genomic target may be associated with clinical benefit. The TAPUR Study, a phase II, prospective, non-randomized, multi-basket, pragmatic clinical trial aims to identify signals of drug activity when Food and Drug Administration (FDA) approved drugs are matched to pre-specified genomic targets in patients with advanced cancer, outside of approved indications., Methods: Patients eligible to participate in TAPUR are ages 12 years and older, with advanced, measurable or evaluable solid tumors, multiple myeloma or B cell non-Hodgkin lymphoma. Eligible participants are matched to any of the sixteen FDA approved study drugs based on protocol specified genomic inclusion and exclusion criteria. Genomic profiling from any Clinical Laboratory Improvement Amendments certified, College of American Pathologists accredited laboratory is acceptable. The treating physician selects the treatment from the available study therapies, or consults with the TAPUR Molecular Tumor Board. Participants are placed into multiple parallel cohorts defined by tumor type, genomic alteration and drug. The primary study endpoint within each cohort is objective response or stable disease of at least 16 weeks duration. Secondary endpoints include safety, progression-free survival and overall survival., Results: More than 1000 participants have thus far been registered and more than 800 treated with a TAPUR study drug. Two study cohorts have permanently closed to enrollment due to lack of anti-tumor activity and 12 have expanded to the second stage of enrollment due to promising preliminary activity., Conclusion: The TAPUR Study will describe the efficacy and toxicity of the targeted drugs used outside of their approved indications when matched to a somatic genomic variant.

Background: With rapid advances in genomic medicine, the complexity of delivering precision medicine to oncology patients across a university health system demanded the creation of a Molecular Tumor Board (MTB) for patient selection and assessment of treatment options. The objective of this report is to analyze our progress to date and discuss the importance of the MTB in the implementation of personalized medicine., Materials and Methods: Patients were reviewed in the MTB for appropriateness for comprehensive next generation sequencing (NGS) cancer gene set testing based on set criteria that were in place. Because profiling of stage IV lung cancer, colon cancer, and melanoma cancers were standard of care, these cancer types were excluded from this process. We subsequently analyzed the types of cases referred for testing and approved with regards to their results., Results: 191 cases were discussed at the MTB and 132 cases were approved for testing. Forty-six cases (34.8%) had driver mutations that were associated with an active targeted therapeutic agent, including BRAF, PIK3CA, IDH1, KRAS , and BRCA1 . An additional 56 cases (42.4%) had driver mutations previously reported in some type of cancer. Twenty-two cases (16.7%) did not have any clinically significant mutations. Eight cases did not yield adequate DNA. 15 cases were considered for targeted therapy, 13 of which received targeted therapy. One patient experienced a near complete response. Seven of 13 had stable disease or a partial response., Conclusions: MTB at University of Alabama-Birmingham is unique because it reviews the appropriateness of NGS testing for patients with recurrent cancer and serves as a forum to educate our physicians about the pathways of precision medicine. Our results suggest that our detection of actionable mutations may be higher due to our careful selection. The application of precision medicine and molecular genetic testing for cancer patients remains a continuous educational process for physicians., Competing Interests: CONFLICTS OF INTEREST None.

Liver cancer is a heterogeneous group of tumors characterized by significant molecular and genomic heterogeneity. The advent of powerful genomic technologies has allowed detection of recurrent somatic alterations in liver cancer, including mutations, copy number alterations as well as changes in transcriptomes and epigenomes, with the potential to translate these data into clinically relevant predictive and prognostic factors. In this review, we discuss recent advances in the application of high-throughput genomic technologies in liver cancer and the integration of such cancer genome profiling data, highlighting specific relevant subgroups and explain how this knowledge can be used in translational clinical research, 'basket trials', molecular tumor boards, targeted therapy and for personalized genomic medicine applications., Competing Interests: Financial & competing interests disclosure The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

Objective: DNA sequencing tests are enabling physicians to interrogate the molecular profiles of patients' tumors, but most oncologists have not been trained in advanced genomics. We initiated a molecular tumor board to provide expert multidisciplinary input for these patients., Materials and Methods: A team that included clinicians, basic scientists, geneticists, and bioinformatics/pathway scientists with expertise in various cancer types attended. Molecular tests were performed in a Clinical Laboratory Improvement Amendments environment., Results: Patients (n = 34, since December 2012) had received a median of three prior therapies. The median time from physician order to receipt of molecular diagnostic test results was 27 days (range: 14-77 days). Patients had a median of 4 molecular abnormalities (range: 1-14 abnormalities) found by next-generation sequencing (182- or 236-gene panels). Seventy-four genes were involved, with 123 distinct abnormalities. Importantly, no two patients had the same aberrations, and 107 distinct abnormalities were seen only once. Among the 11 evaluable patients whose treatment had been informed by molecular diagnostics, 3 achieved partial responses (progression-free survival of 3.4 months, ≥6.5 months, and 7.6 months). The most common reasons for being unable to act on the molecular diagnostic results were that patients were ineligible for or could not travel to an appropriately targeted clinical trial and/or that insurance would not cover the cognate agents., Conclusion: Genomic sequencing is revealing complex molecular profiles that differ by patient. Multidisciplinary molecular tumor boards may help optimize management. Barriers to personalized therapy include access to appropriately targeted drugs., (©AlphaMed Press.)