KRAS and NRAS mutation detection in circulating DNA from patients with metastatic colorectal cancer using BEAMing assay: Concordance with standard biopsy and clinical evaluation.

Patients with metastatic colorectal cancer (mCRC) are routinely screened for either K- and N-RAS to select the appropriate treatment. The present study aimed to evaluate the concordance between K- and NRAS status in the tissue (either primary tumor or metastasis) and the plasma of patients with mCRC and to identify the associations between K- and NRAS mutations in ctDNA and the clinicopathological parameters. Samples from a total of 31 patients with mCRC with measurable disease according to the Response Evaluation Criteria in Solid Tumors were analyzed. For all patients, K- and NRAS status was determined in the tissue by matrix-assisted laser desorption/ionization time of flight mass spectrometry. For the detection of RAS mutations in cell-free tumor DNA also defined as circulating tumor DNA (ctDNA), the OncoBEAM® RAS CRC kit (Sysmex Inostics) was used. A total of 6/31 tissue samples expressed wild-type KRAS, whereas 25/31 presented mutations. In addition, 7/31 plasma samples expressed wild-type KRAS, mutations were detected in 22/31 patients, and for 2/31 patients, the test did not provide a conclusive result. A total of 24/31 patients expressed wild-type NRAS, 6/31 had mutations and 1/21 was not informative. For the KRAS mutational status, a moderate concordance (agreement, 85.18%; Cohen's k, 0.513) between the tissue and plasma analysis was observed; for NRAS, a fair agreement (agreement, 83.33%; Cohen's k, 0.242) was obtained. In conclusion, both tissue and plasma analyses should be performed for the management of patients with mCRC. To better exploit the beads, emulsions, amplification, magnetics (BEAMing) technique in the clinical setting, studies aimed at determining the RAS status to monitor therapy and during follow-up are warranted.

Patient associations and clinical oncology research: how much does a patient's voice really matter?

Background: New trends are emerging in clinical research, such as patient empowerment and an active role in influencing health and research ethics. Patients' involvement is considered pivotal by stakeholders and institutions because they can channel the voice of those they represent, empowering their starring role in the different research activities.Objectives: To obtain an overview of the real involvement of Italian patient associations in clinical research.Methods: In January 2019, the Working Group 'Clinical Research Coordinators' of the Italian Association of Medical Oncology spread an online questionnaire consisting of 16 questions on the active involvement of patient associations in clinical research.Results: The involvement in clinical research working groups, in the organization and implementation of specific activities and training initiatives is very limited (21.7% in both cases), as well as the active involvement in the conduct and/or definition of clinical trials (0.3%). Moreover, few associations (15.2%) have joined projects on patient involvement in clinical research in collaboration with other associations.Discussion: Although the current involvement of the associations may have been somewhat underestimated, there is no doubt that much more can be done in terms of training and identification of common objectives between patients and professionals.

Phase I studies: a test bench for Italian clinical research.

BACKGROUND: The Agenzia Italiana del Farmaco (AIFA) Determination 809/2015 sets all the requirements that clinical units and laboratories must meet in order to conduct phase I studies. Requirements include buildings, equipment, personnel, emergency management, as well as quality requirements defined in a set of standard operating procedures. METHODS: In September 2018, the Italian Association of Medical Oncology working group, Clinical Research Coordinator, created an anonymous survey addressed to 51 medical directors of oncologic/hematologic clinical phase I units and all medical directors of generic and transversal units located in Italy and listed at the AIFA website. RESULTS: Questionnaires from 24 institutions were collected, 9 previously inspected by competent authorities. All surveyed structures are certified to conduct profit studies and 1 is authorized to include healthy volunteers; 15 units implemented a Clinical Trial Quality Team in order to conduct nonprofit studies. At the time of data collection, a total of 398 proposals for phase I trials have been received, more than 50% coming from 3 institutes. A total of 144 phase I studies were active, with a median of 2.5 (Q1-Q3=0-6) studies for each center and asymmetric distribution of proposals. CONCLUSION: The considerable number of proposals received from the interviewed centers indicates that Italy plays an important role in the international pharmaceutical scene, despite bureaucratic procedures that threaten exclusion from decision-making. The AIFA Determination will be an important opportunity to acquire a competitive working approach.

Effect of Contract Research Organization Bureaucracy in Clinical Trial Management: A Model From Lung Cancer.

INTRODUCTION: Contract research organization (CRO) support is largely included in clinical trial management, although its effect in terms of time savings and benefit has not yet been quantified. We performed a retrospective multicenter analysis of lung cancer trials to explore differences in term of trial activation timelines and accrual for studies with and without CRO involvement. MATERIALS AND METHODS: Results regarding study timelines from feasibility data to first patient enrollment were collected from 7 Italian thoracic oncology departments. The final accruals (screened/enrolled patients) are reported. We considered CRO/sponsor-administered and CRO-free trials according to who was responsible for the management of the crucial setup phases. RESULTS: Of 113 trials, 62 (54.9%) were CRO-administered, 34 (30.1%) were sponsor-administered, and 17 (15.0%) were CRO-free. The median time from feasibility invitation to documentation obtainment was 151 days in the CRO-administered trials versus 128 in the sponsor-administered and 120 in the CRO-free trials. The time from document submission to contract signature was 142 days in the CRO-administered versus 128 in the sponsor-administered and 132 in the CRO-free trials. The time from global accrual opening to first patient enrollment was 247 days for the CRO-administered versus 194 in the sponsor-administered and 151 in the CRO-free trials. No significant differences were observed in terms of the median overall timeline: 21 months in the CRO-administered, 15 in the sponsor-administered, and 18 months in the CRO-free studies (P = .29). CONCLUSION: Although no statistically significant differences were identified, the results of our analysis support the idea that bureaucratic procedures might require more time in CRO-administered trials than in sponsor-administered and CRO-free studies. This bureaucratic delay could negatively affect Italian patients' screening and enrollment compared with other countries.