Abstract This phase I, dose-escalation trial evaluates the safety of combining interferon-gamma (IFN-γ) and nivolumab in patients with metastatic solid tumors. Twenty-six patients are treated in four cohorts assessing increasing doses of IFN-γ with nivolumab to evaluate the primary endpoint of safety and determine the recommended phase two dose (RP2D). Most common adverse events are low grade and associated with IFN-γ. Three dose limiting toxicities are reported at the highest dose cohorts. We report only one patient with any immune related adverse event (irAE). No irAEs ≥ grade 3 are observed and no patients require corticosteroids. The maximum tolerated dose of IFN-γ is 75 mcg/m 2 , however based on a composite of safety, clinical, and correlative factors the RP2D is 50 mcg/m 2 . Exploratory analyses of efficacy in the phase I cohorts demonstrate one patient with a complete response, and five have achieved stable disease. Pre-planned correlative assessments of circulating immune cells demonstrate intermediate monocytes with increased PD-L1 expression correlating with IFN-γ dose and treatment duration. Interestingly, post-hoc analysis shows that IFN-γ induction increases circulating chemokines and is associated with an observed paucity of irAEs, warranting further evaluation. ClinicalTrials.gov Trial Registration: NCT02614456.
211 Background: The use of peer-review activities in oncology is not well described as a quality improvement process. We sought to describe current patterns of practice of radiation oncology peer-review across a large Provincial Cancer program and to identifiy barriers to its use. Methods: Ontario cancer centres were surveyed. Survey item responses were typically scored using a 10-point Likert scale. The survey was administered electronically with follow-up reminders as required. The use of free-text for comments elaborating on responses was encouraged. Results: Fourteen (100%) centres responded. All rated the importance of peer-review as at least 8/10 (10=extremely important). Detection of medical error and improvement of planning processes were the highest-rated benefits of peer-review (each median 9/10). Four centres (29%) conducted peer-review in more than 80% of cases treated with curative intent; six (43%) peer-reviewed at least 50% of curative cases. Five centres (36%) reported “always” or “almost always” conducting peer-review prior to the initiation of treatment. Variation was seen in which aspects of a case were typically reviewed (e.g., GTV “almost always” reviewed in 67%; contouring of organs at risk in 50%). Five centres (46% of those with regular peer-review) reported that 5% to 9% of peer-reviewed cases were flagged as requiring a change, whereas 3 centres (27%) reported that < 2% of peer-reviewed cases required a change to be made. Five centres (36%) recorded the outcomes of peer-review on the medical record. Thirteen centres (93%) planned to expand peer-review activities; the two factors rated as most limiting to expanding peer-review were a critical mass of radiation oncologists (median score 6/10), and prioritization of peer review by the program overall (median 5/10). Conclusions: Peer review in radiation oncology practices it is now widely used as a quality assurance activity in Ontario, identifies changes to improve quality in the individual case, and improves departmental process. The development of guidelines and standards for peer-review activities, coupled with effective knowledge translation activities are recommended.
Purpose: It is widely accepted that the quality of IMRT plans relies on individualsˈ planning experiences. RapidArc offers large degrees of freedom in dose shaping. While calculation and optimization take longer time, it is necessary to standardize planning in order to control the quality and efficiency. In this report, we present our progress in this regard in prostate and post‐prostatectomy (prostate bed) radiation therapy. Material and Methods: 12 prostate (78Gy/39) and 10 prostate bed (66Gy/33) pts were retrospectively planned using single arc and double arc respectively to test the standardization templates without interventional adjustment. The highest optimization priority is given to target, followed by sharp dose falloff (NTO in Eclipse) and OARs constrains with step‐down priorities. This priority setting aims to efficiently utilize arc features and produce optimal conformal dose. OARs within beam‐range were used as optimization structures to minimize the impact of patientsˈ anatomical variations on dose limits. The standardized plans were compared to the clinically treated plans which were previously optimized by individual dosimetrists using single arc for prostate and dIMRT for prostate bed. Results: Standardized plans show superiority over clinical plans in target dose, OARs sparing and dose conformity. For prostate, the average rectum D50 was reduced by ∼6Gy from 42Gy to 36Gy while D25 was decreased by 2Gy from 58Gy to 56Gy; target dose, bladder and femoral dose are equivalent. For prostate bed, the average rectum D50 was lowered by ∼5Gy from 37Gy to 32Gy; target dose is more conformal with Dmax being reduced by 1Gy; femoral dose is spared by ∼7Gy and bladder dose is equivalent. Conclusions: Standardizing Arc planning can significantly improve plan quality and planning efficiency. Our center has implemented the procedures. Clinical practice shows the standardized templates are robust and only ∼15% of the plans need individual improvement due to unusual anatomy.
This chapter, ‘Assessing capacity and decision-making’, explores mental capacity and the practical, legal, and ethical components of this common situation; the MCA (Mental Capacity Act) and its five statutory principles: the stages of capacity assessment; assessment of capacity in the context of cognitive problems; making decision for patients lacking capacity; determining patient’s best interests. Determining a patient’s best interests is often a complex area, and one in which family and friends can be uniquely placed to help you make this judgement. However, the relatives’ views have no legal standing in English law, and the decision must be made by the responsible professionals. With the help of excellent case vignettes, this chapter describes advance care planning, lasting power of attorney, IMCA (independent mental capacity advocate), DOLS (deprivation of liberty safeguards), The Court of Protection, and the implications of mental capacity on medical research.
239 Background: Clinical Treatment Decisions in radiation oncology direct the patient’s treatment plans. There is a need for Clinical Decisions to be peer reviewed preferably in real time before the patient plan is completed. Traditional peer review of clinical decisions which ensure high quality patient treatments can be challenging in a busy radiation oncology clinic. Leveraging Electronic Medical Records (EMR) to query standard patient staging and demographics data per disease type allows for efficient peer review of the clinical decision. Methods: Through the use of EMR system (Aria, Varian Medical Systems, Palo Alto CA), data is entered into the radiation oncology chart by the primary radiation oncologist during a patient’s work up. Tools within the EMR have been configured to automatically query patient charts and summarize the data. A second Oncologist runs the query, reviews the data and peer reviews clinical decision for radiotherapy including treatment intent, dose and target contours. The radiation oncologist can then discuss modifications with the original oncologist, or indicate to the dosimetrist to continue planning. Those clinical decisions that are uncertain are escalated to review in a traditional peer review setting. Results: The EMR queries have allowed a shift to real time peer review of clinical decisions. The summary of disease specific staging and demographics data has added to efficiency in clinic in both the oncologists’ ability to complete a timely peer review and the lowering the amount of planning rework. Traditional peer review setting is then used to discuss the controversial and complex cases that would receive the most benefit. Conclusions: The ability to leverage electronic medical record data has made the peer review of clinical decisions in our institution more efficient and therefore the majority can be completed in real time.
This project was designed to harmonise the Royal College of Pathologists, College of American Pathologists and Royal College of Pathologists of Australasia datasets, checklists and structured reporting protocols for examination of radical prostatectomy specimens, with the aim of producing a common, internationally agreed, evidence-based dataset for prostate cancer reporting. The International Collaboration on Cancer Reporting prostate cancer expert review panel analysed the three existing datasets, identifying concordant items and classified these data elements as 'required' (mandatory) or 'recommended' (non-mandatory), on the basis of the published literature up to August 2011. Required elements were defined as those that have agreed evidentiary support at NHMRC level III-2 or above. Consensus response values were formulated for each item. Twelve concordant pathology data elements were identified, and, on review, all but one were included as required elements for tumour staging, grading, or prediction of prognosis. There was minor discordance between the three existing datasets for another eight items, with two of these being added to the required data set. Another 11 elements with a lesser level of evidentiary support were included in the recommended dataset. This process was found to be an efficient method for producing an evidence-based dataset for prostate cancer. Such internationally agreed datasets should facilitate meaningful comparison of benchmarking data, epidemiological studies, and clinical trials.
'%3e%3cpath fill='%23012169' d='M0 0v30h60V0z'/%3e%3cpath stroke='%23fff' stroke-width='6' d='m0 0 60 30m0-30L0 30'/%3e%3cpath stroke='%23C8102E' stroke-width='4' d='m0 0 60 30m0-30L0 30' clip-path='url(%23b)'/%3e%3cpath stroke='%23fff' stroke-width='10' d='M30 0v30M0 15h60'/%3e%3cpath stroke='%23C8102E' stroke-width='6' d='M30 0v30M0 15h60'/%3e%3c/g%3e%3c/svg%3e)
