Cancer Centers In Ontario Research Articles

Update on Practical Management of Early-Stage Non-Small Cell Lung Cancer (NSCLC): A Report from the Ontario Forum

Therapeutic strategies for early-stage non-small cell lung cancer (NSCLC) are advancing, with immune checkpoint inhibitors (ICIs) and targeted therapies making their way into neoadjuvant and adjuvant settings. With recent advances, there was a need for multidisciplinary lung cancer healthcare providers from across Ontario to convene and review recent data from practical and implementation standpoints. The focus was on the following questions: (1) To what extent do patient (e.g., history of smoking) and disease (e.g., histology, tumor burden, nodal involvement) characteristics influence treatment approaches? (2) What are the surgical considerations in early-stage NSCLC? (3) What is the role of radiation therapy in the context of recent evidence? (4) What is the impact of biomarker testing on treatment planning? Ongoing challenges, treatment gaps, outstanding questions, and controversies with the data were assessed through a pre-meeting survey, interactive cases, and polling questions. By reviewing practice patterns across Ontario cancer centers in the context of evolving clinical data, Health Canada indications, and provincial (Cancer Care Ontario [CCO]) funding approvals, physicians treating lung cancer voiced their opinions on how new approaches should be integrated into provincial treatment algorithms. This report summarizes the forum outcomes, including pre-meeting survey and polling question results, as well as agreements on treatment approaches based on specific patient scenarios.

Molecular Classification of Endometrial Cancers Using an Integrative DNA Sequencing Panel.

Adoption of molecular classification in endometrial cancer (EC) into clinical practice remains challenging due to complexity in coordination of multiple assays. We aimed to develop a simple molecular technique to classify ECs into four subgroups using our custom-designed targeted sequencing panel. Patients with newly diagnosed ECs were prospectively recruited from three cancer centres in Ontario, Canada. Using our panel, 181 ECs were sequenced. Variants were analysed for pathogenicity and clinicopathologic information was collected through medical records retrospectively. Of 181, 86 (48%) were mismatch repair deficient (MMRd), of which 62 (72%) harboured MLH1 promoter methylation and 24 (28%) had pathogenic variants in MMR genes. Of single classifiers, three (1.8%) had pathogenic POLE (POLEmut), 15 (9%) had TP53 mutations (p53abn) and 61 (37%) had no specific molecular profile subtype (NSMP). Sixteen (9%) had more than one molecular classifying feature, with eight (4%) MMRd-p53abn, six (3%) POLEmut-MMRd, one (0.5%) POLEmut-MMRd-p53abn and one (0.5%) POLEmut-p53abn. When MMRd group was further subclassified according to mechanism of MMR loss, MLH1 promoter methylated group had worse outcomes than those with somatic MMR pathogenic variants. Our panel can classify ECs into four subgroups through a simplified process and can be implemented reflexively in clinical practice.

Biopsychosocial Associates of Psychological Distress and Post-Traumatic Growth among Canadian Cancer Patients during the COVID-19 Pandemic.

Understanding both the positive and negative psychological outcomes among cancer patients during the pandemic is critical for planning post-pandemic cancer care. This study (1) examined levels of psychological distress and post-traumatic growth (PTG) among Canadian cancer patients during the COVID-19 pandemic and (2) explored variables that were associated with psychological distress and PTG during the pandemic using a biopsychosocial framework. A cross-section survey was undertaken of patients receiving ongoing care at a regional cancer centre in Ontario, Canada, between February and December 2021. Self-reported questionnaires assessing sociodemographic information, social difficulties, psychological distress (depression, anxiety fear of recurrence, and emotional distress), PTG, illness perceptions, and behavioural responses to the pandemic were administered. Disease-related information was extracted from patient health records. Prevalences of moderate to severe levels of depression, anxiety, fear of recurrence and emotional distress were reported by 26.0%, 21.2%, 44.2%, and 50.0% of the sample (N = 104), respectively. Approximately 43% of the sample reported experiencing high PTG, and these positive experiences were not associated with levels of distress. Social factors, including social difficulties, being female, lower education, and unemployment status were prominent associative factors of patient distress. Perceptions of the pandemic as threatening, adopting more health safety behaviours, and not being on active treatment also increased patient likelihood to experience severe psychological distress. Younger age and adopting more health safety behaviours increased the likelihood of experiencing high PTG. The discriminatory power of the predictive models was strong, with a C-statistic > 0.80. Examining both the positive and negative psychological patient outcomes during the pandemic has highlighted the complex range of coping responses. Interventions that adopt a multi-pronged approach to screen and address social distress, as well as to leverage health safety behaviours, may improve the adjustments in the pandemic aftermath.

Patient and Provider Attitudes and Preferences Regarding Early Palliative Care Delivery for Patients with Advanced Gastrointestinal Cancers: A Prospective Survey.

Early integrated palliative care (EIPC) for patients with advanced cancers requires the involvement of family doctors (FDs) and oncologists. We compared attitudes between patients and their providers regarding the delivery of EIPC. Patients with newly diagnosed incurable gastrointestinal (GI) cancer at a tertiary cancer centre in Ontario, Canada, were surveyed using a study-specific instrument regarding the importance of and preferences for accessing support across eight domains of palliative care. Physicians within the circle of care completed a parallel survey for each patient. The concordance between patient and physician responses was analyzed. A total of 66 patients were surveyed (median age 69, 35% female). All had an oncologist, 12% had a specialist palliative care provider (SPC), and 97% had an FD, but only 41% listed the FD as part of the care team. In total, 95 providers responded (oncologist = 68, FD = 21, SPC = 6; response rate 92%; 1-3 physician responses per patient). Disease management and physical concerns were most important to patients. Patients preferred to access care in these domains from oncologists or SPCs. For all other domains, most patients attributed primary responsibility to self or family rather than any healthcare provider. Thus, concordance was poor between patient and physician responses. Across most domains of palliative care, we found low agreement between cancer patients and their physicians regarding responsibilities for care, with FDs appearing to have limited involvement at this stage.

A scoping assessment of dental services at designated head and neck cancer centres in Ontario, Canada

BackgroundDentists serve a crucial role in managing treatment complications for patients with head and neck cancer, including post-radiation caries and oral infection. To date, dental services for head and neck cancer patients in Ontario, Canada have not been well characterized and considerable disparities in allocation, availability, and funding are thought to exist. The current study aims to describe and assess the provision of dental services for head and neck cancer patients in Ontario.MethodsA mixed methods scoping assessment was conducted. A purposive sample of dentist-in-chiefs at each of Ontario’s 9 designated head and neck cancer centres (tertiary centres which meet provincially-set quality and safety standards) was invited to participate. Participants completed a 36-item online survey and 60-minute semi-structured interview which explored perceptions of dental services for head and neck cancer patients at their respective centres, including strengths, gaps, and inequities. If a centre did not have a dentist-in-chief, an alternative stakeholder who was knowledgeable on that centre’s dental services participated instead. Thematic analysis of the interview data was completed using a mixed deductive-inductive approach.ResultsSurvey questionnaires were completed at 7 of 9 designated centres. A publicly funded dental clinic was present at 5 centres, but only 2 centres provided automatic dental assessment for all patients. Survey data from 2 centres were not captured due to these centres’ lack of active dental services. Qualitative interviews were conducted at 9 of 9 designated centres and elicited 3 themes: (1) lack of financial resources; (2) heterogeneity in dentistry care provision; and (3) gaps in the continuity of care. Participants noted concerning under-resourcing and limitations/restrictions in funding for dental services across Ontario, resulting in worse health outcomes for vulnerable patients. Extensive advocacy efforts by champions of dental services who have sought to mitigate current disparities in dentistry care were also described.ConclusionsInequities exist in the provision of dental services for head and neck cancer patients in Ontario. Data from the current study will broaden the foundation for evidence-based decision-making on the allocation and funding of dental services by government health care agencies.

Framework Development: Standardizing Definition of Advanced Practice Radiation Therapy Activities for Clinical Workload Quantification

PurposeAdvanced practice (AP) in radiation therapy (RT) is being implemented around the globe. In an effort to advance the understanding of the similarities and differences in APRT roles in Ontario, Canada, a community of practice (CoP) sought ways to provide quantitative data on the nature of APRT clinical activities and the frequency with which these activities were being executed. MethodsIn 2017, a consensus building project involving 20 APRTs and 14 radiation therapy (RT) department managers in Ontario was completed to establish a mechanism to quantify APRTs’ clinical impact. In Round 1 & 2, expert feedback was gathered to generate an Advanced Practice (AP) Activity List. In Round 3: 20 APRTs completed an online survey to assess the importance and applicability of each AP Activity to their role using Likert scale (0–5). A final AP Activity List & Definitions was generated. Results & discussionRound 1: Forty-seven AP activities were identified. Round 2: 3/14 RT managers provided 145 feedback statements on Round 1 AP Activity List. The working group used RT managers’ feedback to clarify AP activities and definitions, specifically merging 33 unique AP activities to create 11 inclusive AP activities and eliminating 8 activities identified from Round 1. The most inclusive AP activity created was #1 New Patient Consultation, this AP Activity is merged from 7 unique AP activities. Incorporating RT managers’ feedback with the internal AP clinical workload lists from 2 Ontario cancer centres resulted in a revised AP Activity List with 20 AP inclusive activities. Round 3: 14/20 APRTs provided Likert scores on this revised list. The most applicable AP activities (mean score) were #16 Technical Consultation (4.0), #15 Contouring Target Volume (3.8) and #2 Planning Consultation (3.8); the least applicable was #18 MR Applicator Assessment (0.9). ConclusionsThis is the first systematic attempt to build consensus on AP clinical activities. Non-clinical APRT activities related to research, education, innovation, and program development were not in the scope of this project.The Final AP Activity List & Definitions serves as a framework that allows standardized and continuous monitoring of AP clinical activities and impact.

Comprehensive molecular assessment of mismatch repair deficiency in Lynch associated ovarian cancers using next generation sequencing panel

ObjectivesAbnormalities in mismatch repair have been described in ovarian cancer, but few studies have examined the causes of mismatch repair deficiency (MMRd). To address this, we completed targeted mutational and...

Barriers to engagement of patients in medication reconciliation.

362 Background: Medication reconciliation (MedRec) is a process where a detailed medication list is compiled and reviewed with an appropriate health care professional for completeness and drug-drug interactions, then communicated across all of the patient’s healthcare teams. While effective MedRec can minimize the risk of adverse events, uptake in outpatient oncology can be poor. Engagement of patients and caregivers in collection of medication lists through patient portals has been suggested as a potential change idea to improve uptake. To understand barriers and facilitators of patient engagement in the MedRec process through an electronic patient portal we undertook semi structured interviews in a comprehensive cancer center in Ontario, Canada. Methods: Patients in outpatient oncology clinics and chemo-daycare waiting areas were approached to participate in interviews; as we wished to understand barriers both users and non-users of the medication list feature of the patient portal were eligible to participate. Participant recruitment continued until saturation of data was reached. Interviews were carried out virtually following a semi-structured guide between 08/2022 and 12/2022. Interviews were recorded and transcribed verbatim; thematic coding was completed in NVIVO by two members of the study team. Results: A total of 10 patients participated in interviews; participants ranged in age between 30 to 89 years, and all completed post-secondary education. Patients’ emphasized issues with provider/care team communication expressing it was unclear why they were asked to enter medications and did not know if anyone was reviewing the medications entered. Additionally, patients had a fear of inputting erroneous medications resulting in their overall avoidance to use the portal. Portal features such as the use of generic vs trade name medications created lack of clarity for patients when entering medications into the system. Presently, the language is limited to English which may reduce the number of users. Accessibility issues such as font size and overall layout, especially on mobile devices were noteworthy during interviews. Patients recommended the addition of the following features: refill information including requests, medication reminder features via text/email and linkable medication information. Conclusions: Our findings indicate that although patients are using the portal to upload their medication lists, there are technical and systemic improvements that can be made to increase patient usage. In addition to updates to the patient portal to create added value to patients, and improve comprehension and accessibility, patient education is needed to raise awareness of the importance of MedRec and their role in the process and improve buy in.

Treatment times for delivering adjuvant breast radiotherapy at a cancer centre in Ontario, Canada

BackgroundTime is a valuable commodity that impacts hospital flow, patient experience and economic resources. This study aims to identify factors that affect daily treatment time over a course of radiation therapy (RT) in patients who underwent adjuvant breast RT. MethodsIn all adjuvant breast/chestwall RT patients treated from October 2017 to May 2018, daily set-up, beam delivery time, and overall treatment times were collected. A multivariable linear regression analysis was conducted to identify significant predictive factors related to treatment time. A general linear regression model was used to determine whether there was a learning curve effect throughout the course of treatment that decreased treatment time as patient and staff familiarity with the treatment procedure increased. ResultsA total of 567 patients were included with a median age of 61 years. The average overall treatment time for 2-field and 4-field RT was 8.3 (SD 2.4) and 13.1 (SD 5.6) minutes, respectively. Factors that significantly increased overall treatment times in patients prescribed 2-field RT were: bilateral techniques, breath-hold (BH) techniques, prone techniques (PR), reverse decubitus techniques (RD), wide tangents techniques, the use of bolus and number of segments delivered. (p < 0.05). Factors that significantly increased overall treatment times in patients who received 3-field and 4-field RT were: wide tangents volumes, a higher number of monitor units (MUs), bilateral techniques and BH techniques (p < 0.05). Older patients (≥60) who underwent 3-field and 4-field RT demonstrated a statistically significant increase in set-up time (p < 0.0001). Overall treatment time decreased from 10.0 to 9.3 min over the course of treatment, suggesting a minor learning curve (p = 0.009). ConclusionThe use of bilateral RT, BH, PR, RD, wide tangents, bolus, increasing treatment volumes, and increasing plan complexity were associated with increased treatment times. Future research should quantify the impact of other factors (BMI, mobility, patient care assessments, and imaging protocols) and utility of technological tools (time-predicting models, machine learning tools, and operations research models) on treatment time to optimize RT scheduling and improve resource management.

A Cancer Care Ontario Consensus-Based Organizational Guideline for the Planning and Delivery of Spine Stereotactic Body Radiation Therapy Treatment in Ontario

The proposed recommendations are primarily based on the consensus opinion and in-field experience of the Ontario Health/Cancer Care Ontario stereotactic body radiation therapy (SBRT) for Spine Metastasis Guideline Development Group and published literature when available. Primary consideration was given to the perceived benefits for patients and the small likelihood of harm arising from recommendation implementation. Apart from the magnetic resonance imaging (MRI) follow-up strategy, all evidence was considered indirect and was provided by the working group in conjunction with their collective expertise in the field of SBRT.The application of an SBRT program requires a multidisciplinary team consisting of a radiation oncologist, spine surgeon, neuroradiologist, medical physicist, medical dosimetrist, and radiation therapist. In Canada, linear accelerators are the most used treatment delivery units and should follow technology-specific quality assurance procedures. Immobilization technique is location dependant. Treatment planning MRI sequences should be acquired no more than 14 days from the date of treatment. In the case of epidural disease, simulation MRI should be completed no more than 7 days from the date of treatment. After treatment, patients should be followed with routine clinical visits every 3 months for the first year, every 3 to 6 months during years 2 and 3, and every 4 to 6 months thereafter.The recommendations enclosed provide a framework for the minimum requirements for a cancer center in Ontario, Canada to offer SBRT for spine metastases.

Two Listeria monocytogenes outbreaks in a cancer centre: onsite food premises and their potential health risk to patients

BackgroundThis report describes two L. monocytogenes outbreak investigations that occurred in March and September of 2018 and that linked illness to a food premises located in an Ontario cancer centre. The cancer centre serves patients from across the province.MethodsIn Ontario, local public health agencies follow up with all reported laboratory-confirmed cases of listeriosis to identify possible sources of disease acquisition and to carry out investigations, including at suspected food premises. The Canadian Food Inspection Agency (CFIA) is notified of any Listeria-positive food product collected in relation to a case. The CFIA traces Listeria-positive product through the food distribution system to identify the contamination source and ensure the implicated manufacturing facility implements corrective measures.ResultsOutbreaks one and two each involved three outbreak-confirmed listeriosis cases. All six cases were considered genetically related by whole genome sequencing (WGS). In both outbreaks, outbreak-confirmed cases reported consuming meals at a food premises located in a cancer centre (food premises A) before illness onset. Various open deli meat samples and, in outbreak two, environmental swabs (primarily from the meat slicer) collected from food premises A were genetically related to the outbreak-confirmed cases. Food premises A closed as a result of the investigations.ConclusionsWhen procuring on-site food premises, healthcare facilities and institutions serving individuals with immuno-compromising conditions should consider the potential health risk of foods available to their patient population.

Ensuring patient centeredness in upper extremity lymphedema research: Identifying patient-prioritized agenda and preferences

To elicit a patient-prioritized agenda and preferences for upper extremity lymphedema (LE) research. Focus group sessions (FGs) were conducted with English-speaking, adult women (18 years and older) with breast cancer-related LE (BCRL) seeking conservative or surgical care at two tertiary cancer centers in Ontario, Canada. An interview guide was used; women were asked to describe health-related quality of life (HRQL) outcomes that mattered the most to them, followed by their preferences for research study design and for providing patient-reported outcomes measure (PROM) data. Inductive content analysis was used to identify themes and subthemes. A total of 16 women participated in 4 FG sessions (55±9.5 years) and described the impact of LE on their appearance, physical, psychosocial, and sexual well-being. Women emphasized that psychosocial well-being was often not discussed in clinical care and that they were poorly informed of LE risk and care options. Most women said that they would not be willing to be randomized to surgical versus conservative management of LE. They also expressed a preference to complete PROM data electronically. All women emphasized the value of having an open text option alongside PROMs to expand on their concerns. Patient centeredness is key to generating meaningful data and ensuring ongoing engagement in clinical research. In LE, comprehensive PROMs that measure a range of HRQL concerns, especially psychosocial well-being, should be considered. Women with BCRL are reluctant to be randomized to conservative care when a surgical option is available, resulting in implications for planning trial sample size and recruitment.

Biochemical disease control outcomes of stereotactic body radiation therapy (SBRT) or moderate hypo-fractionation (HFRT) for low- and intermediate-risk prostate cancer (PrCa): Retrospective analysis of 12 years of experience at two Canadian cancer centers.

363 Background: SBRT uses highly conformal radiotherapy to deliver high dose per fraction treatment. Advantages of SBRT include short treatment times, decreased costs and limited toxicity. Randomized trial outcomes of 7-fraction SBRT for low or intermediate PrCa were reported but results of studies that compared 5-fraction SBRT with conventional and HFRT are pending. Here, we reviewed the 12-year experience with SBRT and HFRT at the Juravinski and Walker Family Cancer Centers in Ontario. Methods: We reviewed patients with low or intermittent-risk PrCa treated with SBRT alone or HFRT alone in the period of July 2010 and February 2022. Database search criteria included treatments with SBRT 35-40Gy in 5 fractions and HFRT 60-62Gy in 20 fractions. Overall survival (OS), time to biochemical failure (per Phoenix criteria: i.e., 2ng/mL above PSA nadir) and biochemical failure-free survival (bFFS) were reviewed. Kaplan-Meier curves were used to assess OS and bFFS. Results: We identified 314 patients with low or intermediate-risk PrCa who were treated with SBRT and 258 patients who were treated with HFRT. Intermediate-risk category composed 86.0% and 95.7% of the SBRT and HFRT cohorts. ISUP Grade Group (GG) distributions for the SBRT and HFRT patients were: GG1: 19.4% and 9.3%, GG2: 72.9% and 74.0%, and GG3: 7.6% and 16.7%, respectively. OS rates at 5 years were 96.6% for SBRT vs. 95.8% for HFRT-treated patients. The 5-year bFFS rates for SBRT and HFRT were 92.3% and 90.1%, respectively. The 7-year bFFS rate for the SBRT cohort was 90.2%. Mean time to biochemical failure was 40.4 months after SBRT vs. 35.8 months after HFRT. Conclusions: SBRT is an effective treatment option for low to intermediate-risk PrCa with encouraging OS and bFFS rates comparable with HFRT. Pending randomized trial results will determine whether SBRT is the new standard of care for this population.

Impact of Geographical Distance from Quaternary Treatment Center on Clinical Trial Participation, Intensive Induction Chemotherapy, and Outcomes in Patients with Newly Diagnosed Acute Myeloid Leukemia

Introduction: Care for patients with acute myeloid leukemia (AML) is centralized in the Ontario single-payer public healthcare system, with intensive induction chemotherapy and clinical trials only offered at specialized cancer centers with large catchment areas. Methods: We therefore conducted a retrospective single-center review of all AML patients assessed at a large specialized cancer center in Ontario, Canada. Results: Between 2012 and 2017, 1,310 patients were assessed by our center for upfront AML therapy. The median distance was 33.1 km, with 29% of patients living more than 50 km away from the center. There was no significant difference in probability of intensive induction chemotherapy or clinical trial by distance from center, both in univariate and multivariable analysis adjusting for age, sex, cytogenetics and molecular testing, and performance status. There was no significant difference in overall survival by distance from center on univariate and multivariable analysis. Conclusion: In conclusion, geographic distance from treatment center does not appear to impact choice of upfront therapy, participation in clinical trials, or clinical outcomes in this study of newly diagnosed patients with AML treated in a single-payer environment.

UnCHAARTED territory: The role of docetaxel rechallenge following chemohormonal therapy for metastatic castration-sensitive prostate cancer.

To assess the effectiveness of docetaxel rechallenge (DR) for metastatic castration-resistant prostate cancer (mCRPC) following chemohormonal therapy for metastatic castrate-sensitive prostate cancer (mCSPC). Additionally, we sought to define clinical factors predicting treatment response. Retrospective analysis of men treated with docetaxel for mCSPC and then rechallenged in the mCRPC setting from four cancer centers in Ontario, Canada. Prostate specific antigen (PSA) response, progression-free survival (PFS), and overall survival (OS) following DR were evaluated. Fifty five patients were identified between 2015 and 2020. Prior to DR, 94.5% of patients received androgen-receptor axis targeted therapy, 20% received radium-223, and 1.8% received cabazitaxel. Among 54 evaluable patients, 27.8% had a PSA decline ≥50%. Median PFS was 4.1 months (95% CI, 2.1-4.8) and median OS from androgen deprivation therapy initiation was 38.3 months (95% CI, 32.9-41.0). A Gleason Score of ≥8 was an independent predictor of prolonged PFS (HR 0.32, 95% CI, 0.12-0.81; P=0.02). DR following chemohormonal therapy for mCSPC produced a meaningful PSA response in approximately one-quarter of patients, with relatively short PFS. The impact of Gleason Score on docetaxel response warrants further investigation.

A 20-Year Review of the Ontario Radiation Therapy Access to Care Crisis: Lessons Applied to the COVID-19 Pandemic

Purpose/Objective(s)Cancer systems across Canada are struggling with an acute access to care crisis resulting from the COVID-19 pandemic. Policies are being considered and applied across the country to address the backlog of patients needing access to cancer services, including radiation therapy (RT). The purpose of this research was to assess the impact of central (provincial health ministry and cancer agency) and regional (cancer center) policies on access to RT in Ontario between 1997 and 2017, and consider their relevance to today's challenges.Materials/MethodsThe research design was a case study with multiple embedded units. The case was Cancer Care Ontario. The embedded units were four diverse regional cancer centers representing the 14 different Ontario cancer centers. Methods included a document review, longitudinal quantitative data collection, and 43 key informant interviews. The theoretical underpinning was an extension of Kingdon's Multiple Streams Framework, to examine the ‘problem’, ‘policy’ solutions and ‘politics’ surrounding the crisis.ResultsThe access to RT problem started as a wait time issue in the 1990s caused by inadequate RT facility capacity and a shortage of RT specialized staff, and evolved into a shortfall in RT utilization. Thirty-seven policies were identified and categorized as: improving existing RT capacity (n=5), system planning (n=7), performance management (n=6), human resources (HR, n=12), and building new RT capacities (n=7). Ten of the HR policies implemented to address recruitment and retention had mixed success because of implementation and political context issues. Many of these same policies are now being applied across Canada to address access to cancer services during the COVID-19 pandemic.ConclusionA 20-year case study of the Ontario RT access crisis in the 1990s, and the post-crisis periods, offer many useful learnings that can be applied to current policy challenges in access to care due to the ongoing pandemic.

Are mismatch repair deficient endometrial cancer recurrences more salvageable than intact cohort? (272)

Are mismatch repair deficient endometrial cancer recurrences more salvageable than intact cohort? (272)

Molecular classification of endometrial cancers using an integrative DNA sequencing panel (271)

<b>Objectives:</b> The Cancer Genome Atlas (TCGA) has identified four molecular subgroups of endometrial cancers (EC) with distinct differences in prognosis and response to adjuvant treatment. Stratification of patients according to molecular profiles is critical for individualized therapy at diagnosis, but adoption of molecular classification into clinical practice remains challenging due to the complexity and costs associated with sequencing. We aimed to develop a simple and affordable molecular technique to classify EC into four TCGA subgroups using our high-depth targeted sequencing panel. <b>Methods:</b> Women with newly diagnosed EC were prospectively recruited from three cancer centers in Ontario, Canada, between 2015 and 2018. Tumors were reflexively assessed for mismatch repair (MMR) protein expression by immunohistochemistry (IHC). Using our custom-designed panel, 181 formalin-fixed paraffin-embedded (FFPE) EC samples were sequenced. Our panel was able to identify somatic mutations, copy number variants, insertions and deletions, copy neutral loss of heterozygosity, structural rearrangements, and promoter methylation from a single aliquot of DNA. Variants were analyzed for pathogenicity, and clinical-pathologic information was collected through medical records. <b>Results:</b> Of 181, 86 (48%) were classified into microsatellite instability-high/hypermutated cohort (MSI-h or MMRd), of which 62 (72%) harbored <i>MLH1</i> promoter methylation, and 24 (27%) had pathogenic variants in MMR genes. Concordance with clinical IHC and methylation testing results was high at 99%. Of cases with a single classifier, three (1.6%; <i>n</i>=181) had pathogenic <i>POLE</i> exonuclease domain mutation (<i>POLE</i>mut), 15 (8%) had a pathogenic p53 variant (p53mut), and 61 (34%) had no specific molecular profile subtype (NSMP). Sixteen (9%; <i>n</i>=181) had more than one molecular classifying feature, with eight (4%) having MMRd-p53mut, six (3%) with MMRd-<i>POLE</i>mut, one (0.5%) with MMRd-<i>POLE</i>mut-p53mut, and one (0.5%) with <i>POLE</i>mut-p53mut. Overall, there were 11 (6%) with <i>POLE</i> mutations (three single and nine multiple classifiers). Survival outcomes of MMRd, <i>POLEmut,</i> p53mut, and NSMP groups stratified similarly to TCGA data, but when the MMRd group was further subclassified according to the mechanism of MMR loss, the MLH1 promoter methylated group did worse than those with somatic MMR pathogenic variants (5-year OS: 0.72 [0.57-0.92] vs 1.00 [1.00-1.00]; p=0.013 and RFS: 0.70 [0.58-0.85] vs 0.92 [0.82-1.00]; p=0.032). In contrast, those with somatic MMR pathogenic variants had similar outcomes to the <i>POLE</i>mut subtype (p=0.396) (Figure 1). <b>Conclusions:</b> Our NGS panel can classify EC into four TCGA subgroups through a simplified process and can be implemented reflexively in clinical practice. The higher rate of multiple classifiers (9%) in this study warrants further investigation. The difference in survival between MLH1 methylated group within MMRd cohort suggests that further subclassification may be required for accurate prognostication.

Challenges in virtual collection of patient-reported data: a prospective cohort study conducted in COVID-19 era.

Prior to the COVID-19 pandemic, patients attending ambulatory clinics at cancer centers in Ontario completed the Edmonton Symptom Assessment Scale (ESAS) at each visit. At our center, completion was via touchpad, with assistance from clinic volunteers. As of March 2020, clinic appointments were conducted virtually when possible and touch pads removed. We anticipated a negative impact on the collection of patient-reported outcomes (PROs) and the recognition of severe symptoms.MethodsWe performed a prospective cross-sectional cohort study to investigate remote ESAS completion by patients with appointments at a weekly surgical oncology clinic. Patients in the initial study cohort were asked to complete and return the ESAS virtually (V). Given low completion rates, the ensuing cohort was asked to complete a hard-copy (HC) ESAS. For the final cohort, we provided remote, personal mentorship by a member of the care team to support virtual electronic ESAS completion (virtual-mentored (VM) cohort).ResultsBetween May and July 2020, a total of 174 patient encounters were included in the study. For the V cohort, 20/46 patients (44%) successfully completed and returned the electronic ESAS, compared to 49/50 (98%) for the HC cohort. For the VM cohort, the overall completion rate was 74% (58/78); however, 12 of these 58 patients did not independently complete a virtual ESAS. Virtual questionnaire completion was not predicted by age, sex, or tumor site, although patients who completed the ESAS were more likely to be in active management rather than surveillance (p = 0.04). Of all completed forms, 42% revealed a depression score of ≥2, and 27% an anxiety score of ≥4.ConclusionsWe identified significant barriers to the virtual completion of ESAS forms, with a lack of predictive variables. The severe degree of psychological distress reported by ~50% of respondents demonstrates the need for ongoing regular collection/review of these data. Innovative solutions are required to overcome barriers to the virtual collection of PROs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s00520-022-07191-3.

Quality-of-Life Outcomes and Toxic Effects Among Patients With Cancers of the Uterus Treated With Stereotactic Pelvic Adjuvant Radiation Therapy

Adjuvant radiation plays an important role in reducing locoregional recurrence in patients with uterine cancer. Although hypofractionated radiotherapy may benefit health care systems and the global community while decreasing treatment burden for patients traveling for daily radiotherapy, it has not been studied prospectively nor in randomized trials for treatment of uterine cancers, and the associated toxic effects and patient quality of life are unknown. To evaluate acute genitourinary and bowel toxic effects and patient-reported outcomes following stereotactic hypofractionated adjuvant radiation to the pelvis for treatment of uterine cancer. The Stereotactic Pelvic Adjuvant Radiation Therapy in Cancers of the Uterus (SPARTACUS) phase 1/2 nonrandomized controlled trial of patients accrued between May 2019 and August 2021 was conducted as a multicenter trial at 2 cancer centers in Ontario, Canada. In total, 61 patients with uterine cancer stages I through III after surgery entered the study. Stereotactic adjuvant pelvic radiation to a dose of 30 Gy in 5 fractions administered every other day or once weekly. Assessments of toxic effects and patient-reported quality of life (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and endometrial EN24) were collected at baseline, fractions 3 and 5, and at 6 weeks and 3 months of follow-up. Descriptive analysis was conducted, calculating means, SDs, medians, IQRs, and ranges for continuous variables and proportions for categorical variables. Univariate generalized linear mixed models were generated for repeated measurements on the quality-of-life scales. A total of 61 patients were enrolled (median age, 66 years; range, 51-88 years). Tumor histologic results included 39 endometrioid adenocarcinoma, 15 serous or clear cell, 3 carcinosarcoma, and 4 dedifferentiated. Sixteen patients received sequential chemotherapy, and 9 received additional vault brachytherapy. Median follow-up was 9 months (IQR, 3-15 months). Of 61 patients, worst acute gastrointestinal tract toxic effects of grade 1 were observed in 33 patients (54%) and of grade 2 in 8 patients (13%). For genitourinary worst toxic effects, grade 1 was observed in 25 patients (41%) and grade 2 in 2 patients (3%). One patient (1.6%) had an acute grade 3 gastrointestinal tract toxic effect of diarrhea at fraction 5 that resolved at follow-up. Only patient-reported diarrhea scores were both clinically (scores ≥10) and statistically significantly worse at fraction 5 (mean [SD] score, 35.76 [26.34]) compared with baseline (mean [SD] score, 6.56 [13.36]; P < .001), but this symptom improved at follow-up. Results of this phase 1/2 nonrandomized controlled trial suggest that stereotactic hypofractionated radiation was well tolerated at short-term follow-up for treatment of uterine cancer. Longer follow-up and future randomized studies are needed to further evaluate this treatment. ClinicalTrials.gov Identifier: NCT04866394.