Reduced Staphylococcus Abundance Characterizes the Lesional Microbiome of Actinic Keratosis Patients after Field-Directed Therapies.

Skin microbiome dysbiosis with a Staphylococcus overabundance is a feature of actinic keratosis (AK) and squamous skin carcinoma (SCC) patients. The impact of lesion-directed treatments for AK lesions such as diclofenac (DIC) and cold atmospheric plasma (CAP) on the lesional microbiome is not established. We studied 321 skin microbiome samples of 59 AK patients treated with DIC 3% gel versus CAP. Microbial DNA from skin swabs taken before start of treatment (week 0), at the end of the treatment period (week 24), and 3 months after end of treatment (week 36) was analyzed after sequencing the V3/V4 region of the 16S rRNA gene. The relative abundance of S. aureus was scrutinized by a tuf gene specific TaqMan PCR assay. The total bacterial load and both, relative and absolute abundance of Staphylococcus genus was reduced upon both therapies at week 24 and 36 compared to week 0. Notably, the lesional microbiome of patients responding to CAP therapy at week 24 was characterized by an increased relative abundance of Corynebacterium genus compared to nonresponders. A higher relative abundance of Staphylococcus aureus at week 36 was a feature of patients classified as nonresponders for both treatments 12 weeks after therapy completion. The reduction of the Staphylococcus abundance after treatment of AK lesions and alterations linked to treatment response encourage further studies for investigation of the role of the skin microbiome for both, the carcinogenesis of epithelial skin cancer and its function as predictive therapeutic biomarker in AK. IMPORTANCE The relevance of the skin microbiome for development of actinic keratosis (AK), its progression into squamous skin cancer, and for field-directed treatment response is unknown. An overabundance of staphylococci characterizes the skin microbiome of AK lesions. In this study, analyses of the lesional microbiome from 321 samples of 59 AK patients treated with diclophenac gel versus cold atmospheric plasma (CAP) revealed a reduced total bacterial load and reduced relative and absolute Staphylococcus genus abundance upon both treatments. A higher relative Corynebacterium abundance was a feature of patients classified as responders at the end of CAP-treatment period (week 24) compared with nonresponders and the Staphylococcus aureus abundance of patients classified as responders 3 months after treatment completion was significantly lower than in nonresponders. The alterations of the skin microbiome upon AK treatment encourage further investigations for establishing its role for carcinogenesis and its function as predictive biomarker in AK.

Delayed Treatment of Retroclival Meningioma in a 70-year-old Female.

We report a case of a 70-year-old female who presented with a four-year history of progressive headaches in the occipital area. MRI revealed a right inferior clival meningioma. Treatment was delayed for over a year due to multiple referrals resulting in the development of new symptoms including decreased balance, generalized weakness, and difficulty swallowing.

Attitudes Towards Research During Residency Training: a Survey of Canadian Radiation Oncology Residents and Program Directors.

Radiation oncologists require clinical appraisal and research methodology skills, yet it is unclear how to develop these competencies during residency. We sought to attain a deeper understanding of the barriers that limit, as well as the factors that promote, engaging in research/scholarly activity during radiation oncology residency training in Canada. Following ethics approval, online surveys were circulated to all Canadian Radiation Oncology program directors and residents. Unidentifiable demographics, prior research experience, and descriptions of current research environment and barriers to engaging in research and scholarly activities were collected. Thirty-three percent (35/105) of residents and 71% (10/14) of program directors responded. Ninety-seven percent of residents, and 90% of program directors, agreed or strongly agreed that research/scholarly activity was an important part of residency training. While 66% of residents felt that there was a lack of protected time for research/scholarly activity, only 20% of program directors agreed this was a barrier (p = 0.011). While 94% of residents thought mentorship was important to completing high-quality research/scholarly activity, only 48% of respondents had a mentor. The highest barriers to completing research/scholarly activity projects were lack of protected time (for both residents and faculty), high resident clinical workload, and lack of experience in research skills. Canadian Radiation Oncology residents expressed strong enthusiasm to participate in research/scholarly activity, yet lack of protected time and competing demands were identified as major barriers. We suggest programs offer more protected time for research/scholarly activity, provide optional research methodology training, and support meaningful mentorship relationships.

Transition to practice in radiation oncology: Mind the gap.

INTRODUCTION: Physicians entering independent practice often express apprehension in managing the non-clinical aspects of practice. This study examined the perceived preparedness of radiation oncology (RO) residents for independent practice, identified education gaps, and discussed how these deficiencies could be addressed. MATERIALS AND METHODS: Focus groups with senior RO residents, fellows, new-to-practice radiation oncologists (ROs), and residency program directors were conducted. Data were coded using the Canadian Medical Education Directives for Specialists (CanMEDS) competencies using thematic analysis. RESULTS: Commonly reported gaps in the transition to practice (TtP) for ROs were lack of experience with: practice management, understanding the structure and function of the health care system and how it varies by jurisdiction, financial planning, effective communication and collaboration with other health care team members, creation of accurate and timely documentation, and radiotherapy problem-solving related to treatment planning and evaluation. Suggestions to address these challenges included use of mentorship, educational resources, courses, simulation-based medical education, improved graded responsibility, resident longitudinal clinics, and formal curricula in radiation therapy planning and evaluation. CONCLUSION: There are gaps in TtP education for RO trainees with opportunities for enrichment through the forthcoming implementation of a competency-based medical education framework in 2019. The gap in perceived competency in physician-related radiotherapy tasks may be caused by the complex interaction of clinical workflow processes, people and technology that has led to ineffective integration of trainees. The data are informative to medical education leaders for the development of comprehensive TtP curricula.

Describing a Process for Creating a Patient Visible Quality Educational Display to Increase Patient Engagement in Radiation Oncology Throughout the Canadian Maritimes Provinces.

Here, we report the process for creating a patient visible quality educational display to highlight the collaborative quality working practices of Radiation Oncology clinicians and staff in the main Radiotherapy Centers throughout three Canadian provinces. These processes are often not visible to patients yet they speak directly to the standards of care delivered at these centers. The Canadian Partnership for Quality Radiotherapy (CPQR) Quality Assurance Guidelines for Canadian Radiation Treatment Programs guided this process. The display slides created were approved by the local Radiation Oncology departmental leadership for each participating medical center as well as patient focus groups and revised with feedback from both perspectives. Of 27 patients/families who evaluated the resulting educational patient display, 70% expressed high engagement in the information presented, and 81% felt the display will be of interest to patients receiving radiotherapy treatment. Patients/families surveyed reported that the displayed content made them feel more informed and more comfortable with their treatments. Survey data from this project indicates that increasing transparency and deepening patient education about the quality working practices behind radiotherapy treatments has the potential to empower patients receiving radiotherapy and increase their confidence in the care they are receiving.

Transition to practice: creation of a transitional rotation for radiation oncology.

BACKGROUND: Implementation of Competence by Design (CBD) will require residency training programs to develop formalized "Transition to Practice" (TTP) experiences. A multidisciplinary group of Radiation Oncology stakeholders from tertiary care centres in Atlantic Canada were surveyed regarding a proposed TTP rotation. METHODS: The survey asked participants to quantitatively rank various learning objectives based on defined CanMEDS skills that are expected to be mastered by a graduating resident. Mean perceived importance scores were calculated for each objective as well as for their CanMEDS category. Specific written qualitative feedback was also collected. RESULTS: The survey was circulated to 59 participants with a response rate of 73%. The three objectives with the highest mean importance score were "Independently assessing and managing patients seen in consultation," "Developing and demonstrating communication skills with patients at an advanced level," and "Independently assessing and managing follow up patients," respectively from highest to lowest. The CanMEDS roles with the highest importance score was "Communicator." CONCLUSION: Quantitative and qualitative data from a multidisciplinary survey based on CanMEDS roles guided the implementation of a TTP rotation for PGY-5 residents at a tertiary care centre in Atlantic Canada. These results may be relevant to other training programs developing TTP experiences.

Radiation therapy quality indicators for invasive breast cancer.

BACKGROUND AND PURPOSE: Radiation therapy (RT) for breast cancer has evolved considerably over the past two decades. A concise list of optimal care indexes is lacking. The purpose of this project was to generate a suite of quality of care indicators for breast cancer RT. MATERIALS AND METHODS: A modified Delphi approach was used including a comprehensive literature and guideline review (1995-2015), an initial review of potential quality indicators (QIs) by a steering committee, a survey of Canadian Radiation Oncologists, and a face-to-face consensus development meeting with breast cancer experts to develop a list of breast RT quality indicators. RESULTS: The literature review identified 163 potential QIs, which was reduced to 73 by the steering committee. After all rounds of the Delphi process the final suite included 33 QIs. Of these, 28 (85%) received at least 80% acceptance from the Radiation Oncologists who participated in the final online survey. CONCLUSIONS: A suite of measureable RT quality indicators to be considered during management of invasive breast cancer was developed. These indicators could be used to assess the quality and consistency of breast cancer RT practices.

Use of Protoporphyrin Fluorescence to Determine Clinical Target Volume for Non-melanotic Skin Cancers Treated with Primary Radiotherapy.

PURPOSE: Non-melanotic skin cancers remain the most commonly diagnosed cancers. Radiotherapy and surgery are the most common treatment options. Radiotherapy has a recurrence rate of up to 20% for basal or squamous cell cancers. One of the difficulties is to determine the extent of disease for poorly demarcated tumors. This study utilizes protoporphyrin (PpIX) fluorescence to provide information on the extent of subclinical disease for poorly demarcated tumors treated with radiotherapy. MATERIALS AND METHODS: For 33 patients, PpIX photo-delineation was used to determine the clinical target volume (CTV2), which was compared to current conventional margins used to account for microscopic disease. RESULTS: The use of PpIX photo-delineation demonstrated a significantly larger CTV of 15 mm compared to the conventional 10 mm (p = 0.03) for poorly demarcated lesions. A larger CTV was also demonstrated with PpIX photo-delineation for all basal cell carcinomas (13 mm, p = 0.03) as well as for non-nasal lesions (14 mm, p = 0.04). A trend towards an increased CTV was also noted for squamous cell carcinomas (16 mm, p = 0.19) and nasal primary sites (14 mm, p = 0.11). Nasal primary malignancies had multifocal PpIX uptake in 94% of cases. There was one case of local recurrence and one case of distant recurrence, with an average follow-up time of 22 months. CONCLUSIONS: The margins currently used to account for subclinical disease may underestimate the extent of microscopic spread for poorly demarcated tumors. Longer follow-up with larger pools of patients are necessary to determine if using PpIX photo-delineation translates into significantly improved clinical outcomes.

Categorizing segmentation quality using a quantitative quality assurance algorithm.

INTRODUCTION: Obtaining high levels of contouring consistency is a major limiting step in optimizing the radiotherapeutic ratio. We describe a novel quantitative methodology for the quality assurance (QA) of contour compliance referenced against a community set of contouring experts. METHODS: Two clinical tumour site scenarios (10 lung cases and one prostate case) were used with QA algorithm. For each case, multiple physicians (lung: n = 6, prostate: n = 25) segmented various target/organ at risk (OAR) structures to define a set of community reference contours. For each set of community contours, a consensus contour (Simultaneous Truth and Performance Level Estimation (STAPLE)) was created. Differences between each individual community contour versus the group consensus contour were quantified by consensus-based contouring penalty metric (PM) scores. New observers segmented these same cases to calculate individual PM scores (for each unique target/OAR) for each new observer-STAPLE pair for comparison against the community and consensus contours. RESULTS: Four physicians contoured the 10 lung cases for a total of 72 contours for quality assurance evaluation against the previously derived community consensus contours. A total of 16 outlier contours were identified by the QA system of which 11 outliers were due to over-contouring discrepancies, three were due to over-/under-contouring discrepancies, and two were due to missing/incorrect nodal contours. In the prostate scenario involving six physicians, the QA system detected a missing penile bulb contour, systematic inner-bladder contouring, and under-contouring of the upper/anterior rectum. CONCLUSION: A practical methodology for QA has been demonstrated with future clinical trial credentialing, medical education and auto-contouring assessment applications.

Assessment and improvement of radiation oncology trainee contouring ability utilizing consensus-based penalty metrics.

INTRODUCTION: The objective of this study was to develop and assess the feasibility of utilizing consensus-based penalty metrics for the purpose of critical structure and organ at risk (OAR) contouring quality assurance and improvement. METHODS: A Delphi study was conducted to obtain consensus on contouring penalty metrics to assess trainee-generated OAR contours. Voxel-based penalty metric equations were used to score regions of discordance between trainee and expert contour sets. The utility of these penalty metric scores for objective feedback on contouring quality was assessed by using cases prepared for weekly radiation oncology radiation oncology trainee treatment planning rounds. RESULTS: In two Delphi rounds, six radiation oncology specialists reached agreement on clinical importance/impact and organ radiosensitivity as the two primary criteria for the creation of the Critical Structure Inter-comparison of Segmentation (CriSIS) penalty functions. Linear/quadratic penalty scoring functions (for over- and under-contouring) with one of four levels of severity (none, low, moderate and high) were assigned for each of 20 OARs in order to generate a CriSIS score when new OAR contours are compared with reference/expert standards. Six cases (central nervous system, head and neck, gastrointestinal, genitourinary, gynaecological and thoracic) then were used to validate 18 OAR metrics through comparison of trainee and expert contour sets using the consensus derived CriSIS functions. For 14 OARs, there was an improvement in CriSIS score post-educational intervention. CONCLUSIONS: The use of consensus-based contouring penalty metrics to provide quantitative information for contouring improvement is feasible.

A Phase II trial of arc-based hypofractionated intensity-modulated radiotherapy in localized prostate cancer.

PURPOSE: To evaluate acute and late genitourinary (GU) and gastrointestinal (GI) toxicity and biochemical control of hypofractionated, image-guided (fiducial markers or ultrasound guidance), simplified intensity-modulated arc therapy for localized prostate cancer. METHODS AND MATERIALS: This Phase II prospective clinical trial for T1a-2cNXM0 prostate cancer enrolled 66 patients who received 63.2 Gy in 20 fractions over 4 weeks. Fiducial markers were used for image guidance in 30 patients and daily ultrasound for the remainder. Toxicity was scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. RESULTS: Median follow-up was 36 months. Acute Phase Grade 2 and 3 toxicity was 34% and 9% for GU vs. 25% and 10% for GI symptoms. One Grade 4 acute GI toxicity occurred in a patient with unrecognized Crohn's disease. Late Grade 2 and 3 toxicity for GU was 14% and 5%, and GI toxicity was 25% and 3%. One late GI Grade 4 toxicity was observed in a patient with significant comorbidities (anticoagulation, vascular disease). Acute GI toxicity ≥ Grade 2 was shown to be a predictor for late toxicity Grade ≥ 2 (p < 0.001). The biochemical disease-free survival at 3 years was 95%. CONCLUSIONS: Hypofractionated simplified intensity-modulated arc therapy radiotherapy given as 63.2 Gy in 20 fractions demonstrated promising biochemical control rates; however, higher rates of acute Grade 3 GU and GI toxicity and higher late Grade 2 GU and GI toxicity were noted. Ongoing randomized controlled trials should ultimately clarify issues regarding patient selection and the true rate of severe toxicity that can be directly attributed to hypofractionated radiotherapy.