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Background: Strategies to minimize the impact of the COVID-19 pandemic led to a reduction in diagnostic testing. It is important to assess the magnitude and duration of this impact to plan ongoing care and avoid long-lasting impacts of the pandemic. Objective: We examined the association between the COVID-19 pandemic and the rate of diagnostic tests for breast, cervical, and colorectal cancer in Manitoba, Canada. Design and Participants: A population-based, cross-sectional study design with an interrupted time series analysis was used that included diagnostic tests from January 1, 2015 until August 31, 2022. Setting: Manitoba, Canada. Main Outcomes: Outcomes included mammogram, breast ultrasound, colposcopy, and colonoscopy rates per 100,000. Cumulative and percent cumulative differences between the fitted and counterfactual number of tests were estimated. Mean, median, and 90th percentile number of days from referral to colonoscopy date by referral type (elective, semiurgent, urgent) were determined. Results: In April 2020, following the declaration of the COVID-19 public health emergency, bilateral mammograms decreased by 77%, unilateral mammograms by 70%, breast ultrasounds by 53%, colposcopies by 63%, and colonoscopies by 75%. In Winnipeg (the largest urban center in the province), elective and semiurgent colonoscopies decreased by 76% and 39%, respectively. There was no decrease in urgent colonoscopies. As of August 2022, there were an estimated 7270 (10.7%) fewer bilateral mammograms, 2722 (14.8%) fewer breast ultrasounds, 836 (3.3%) fewer colposcopies, and 11 600 (13.8%) fewer colonoscopies than expected in the absence of COVID-19. As of December 2022, in Winnipeg, there were an estimated 6030 (23.9%) fewer elective colonoscopies, 313 (2.6%) fewer semiurgent colonoscopies, and 438 (27.3%) more urgent colonoscopies. Conclusions: In Manitoba, the COVID-19 pandemic was associated with sizable decreases in diagnostic tests for breast, colorectal, and cervical cancer. Two and a half years later, there remained large cumulative deficits in bilateral mammograms, breast ultrasounds, and colonoscopies. [ABSTRACT FROM AUTHOR]

Background: Breast-conserving therapy is the standard of care for ductal carcinoma in situ (DCIS). Debate on what constitutes a satisfactory margin persists. This study aimed to identify predictors of residual disease at re-excision. Methods: This is a population-based retrospective cohort study of women with DCIS who underwent a lumpectomy between 2007 and 2017 in Manitoba, with close (≤2 mm) or positive margins that led to re-excision. Results: The DCIS re-excision rate was 29.3% for 1001 patients. 63.2% of patients were found to have residual disease on re-excision. On univariable analysis, the size, margin status, number of positive margins, type of second surgery, and Van Nuys Prognostic Index score were associated with residual disease on re-excision. The size of DCIS and the number of positive margins remained statistically significant on multivariable analysis. Conclusions: Re-excision should be rationalized by considering the predictors of residual disease in conjunction with other factors. [ABSTRACT FROM AUTHOR]

Background Few studies have investigated the impact of the COVID-19 pandemic on cancer survival. Those studies that have included pandemic vs prepandemic comparisons can mask differences during different periods of the pandemic such as COVID-19 waves. The objective of this study was to investigate the impact of the COVID-19 pandemic on cancer survival using an interrupted time series analysis and to identify time points during the pandemic when observed survival deviated from expected survival. Methods A retrospective population-based cohort study that included individuals diagnosed with cancer between January 2015 and September 2021 from Manitoba, Canada, was performed. Interrupted time series analyses with Royston–Parmar models as well as Kaplan–Meier survival estimates and delta restricted mean survival times at 1 year were used to compare survival rates for those diagnosed before and after the pandemic. Analyses were performed for 11 cancer types. Results Survival at 1 year for most cancer types was not statistically different during the pandemic compared with prepandemic except for individuals aged 50-74 years who were diagnosed with lung cancer from April to June 2021 (delta restricted mean survival times = −31.6 days, 95% confidence interval [CI] = −58.3 to −7.2 days). Conclusions With the exception of individuals diagnosed with lung cancer, the COVID-19 pandemic did not impact overall 1-year survival in Manitoba. Additional research is needed to examine the impact of the pandemic on long-term cancer survival. [ABSTRACT FROM AUTHOR]

Background: Although therapy for limited-stage small-cell lung cancer (LS-SCLC) is administered with curative intent, most patients relapse and eventually die of recurrent disease. Chemotherapy (CT) with concurrent radiotherapy (RT) remains the standard of care for LS-SCLC; however, this could evolve in the near future. Therefore, understanding the current prognostic factors associated with survival is essential. Objective: This real-world analysis examines factors associated with long-term survival in patients with LS-SCLC treated with CT in Manitoba, Canada. Methods: A retrospective cohort study was conducted using Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years and had cytologically confirmed LS-SCLC diagnosed between January 1, 2004, and December 31, 2018, for which they received CT ± RT. Baseline patient, disease, and treatment characteristics and survival duration, characterized as short (<6 months), medium (6−24 months), and long term (>24 months), were extracted. Overall survival (OS) was estimated at one, two, and five years and assessed using Kaplan-Meier methods and Cox proportional hazards models. Results: Over the 15-year study period, 304 patients met the eligibility criteria. Long-term survivors comprised 39.1% of the cohort; at diagnosis, this subgroup was younger, more likely to have Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, and have normal lactate dehydrogenase, sodium, and hemoglobin levels. OS estimates for the entire cohort at one, two, and five years were 66%, 38%, and 18%, respectively. In the ECOG PS 0 subgroup, OS estimates at one, two, and five years were 85%, 52%, and 24%, respectively; OS estimates were 60%, 35%, and 17%, respectively, for ECOG PS 1 −2 and were 47%, 23%, and 10%, respectively, for ECOG PS 3−4. OS was significantly higher among patients with normal serum sodium and hemoglobin levels than those with abnormal levels. Univariable hazard regression models found that ECOG PS, age at diagnosis, receipt of prophylactic cranial irradiation (PCI), and thoracic RT were associated with survival. On multivariable hazard regression, ECOG PS and receipt of PCI were associated with survival. Conclusion: Survival for greater than two years in patients with LS-SCLC treated with CT ± RT was associated with ECOG PS and receipt of PCI. [ABSTRACT FROM AUTHOR]

Introduction: Health care in Manitoba, Canada is divided into five regions, each with unique geographies, demographics, health care access, and health status. COVID‐19‐related restrictions and subsequent responses also differed by region. To understand the impact of the pandemic on cancer incidence in the context of these differences, we examined age‐standardized cancer incidence rates by region over time before and after the COVID‐19 pandemic. Methods: We used a population‐based quasi‐experimental study design, population‐based data, and an interrupted time series analysis to examine the rate of new cancer diagnoses before (January 2015 until December 2019) and after the start of COVID‐19 and the interventions implemented to mitigate its impact (April 2020 until December 2021) by region. Results: Overall cancer incidence differed by region and remained lower than expected in Winnipeg (4.6% deficit, 447 cases), Prairie Mountain (6.9% deficit, 125 cases), and Southern (13.0% deficit, 238 cases). Southern was the only region that had a significantly higher deficit in cases compared to Manitoba (ratio 0.92, 95% CI 0.86, 0.99). Breast and colorectal cancer incidence decreased at the start of the pandemic in all regions except Northern. Lung cancer incidence decreased in the Interlake‐Eastern region and increased in the Northern region. Prostate cancer incidence increased in Interlake‐Eastern. Conclusions: The impact of the COVID‐19 pandemic on cancer incidence differed by region. The deficit in the number of cases was largest in the southern region and was highest for breast and prostate cancers. Cancer incidence did not significantly decrease in the most northern, remote region. [ABSTRACT FROM AUTHOR]

The article discusses a synthetic protein-based "winner-take-all" neural network that controls cell fate decisions by classifying multiple inputs and regulating apoptosis. Topics discussed include the implementation of protein-level synthetic circuits, the use of coiled-coil heterodimers for modular design, and the potential applications in cell and gene therapies for improved safety and performance.

Background: Extensive-stage small-cell lung cancer (ES-SCLC) is an incurable cancer with poor prognosis in which characteristics predictive of long-term survival are debated. The utility of agents such as immune checkpoint inhibitors highlights the importance of identifying key characteristics and treatment strategies that contribute to long-term survival and could help guide therapeutic decisions. Objective: This real-world analysis examines the characteristics, treatment patterns, and clinical outcomes of patients receiving chemotherapy without immunotherapy for ES-SCLC in Manitoba, Canada. Methods: A retrospective cohort study assessed patient characteristics, treatment, and survival duration (short: <6 months; medium: 6-24 months; long: >24 months) using the Manitoba Cancer Registry and CancerCare Manitoba records. Eligible patients were aged >18 years with cytologically confirmed ES-SCLC diagnosed between January 1, 2004, and December 31, 2018, and received cytotoxic chemotherapy (CT). The one-, two-, and five-year probabilities of overall survival (OS) were assessed relative to patient, disease, and treatment characteristics using Kaplan-Meier methods and Cox proportional hazards models. Results: This analysis included 537 patients. Cisplatin was used in 56.1% of patients, 45.6% received thoracic radiotherapy (RT), and few received prophylactic cranial irradiation (PCI). In the overall cohort, one-, two- and fiveyear OS rates were 26%, 8%, and 3%, respectively. For patients with Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, OS rates at one, two, and five years were 43%, 17%, and 10%, respectively, vs. 27%, 8%, and 2% for those with ECOG PS 1-2, and 16%, 3%, and 3% for those with ECOG PS 3-4. In long-term survivors, ECOG PS scores were lower and abnormal laboratory test results were less frequent. Overall, 74.4% of long-term survivors received thoracic RT and 53.5% received PCI. Known poor prognostic factors -- including brain/liver metastases, high lactate dehydrogenase (LDH), abnormal sodium, and low hemoglobin levels -- were less common but still seen in longterm survivors. Conclusion: Although rare, patients with ES-SCLC may experience long-term survival with CT ± thoracic RT ± PCI. Factors predicting long-term survival include traditional prognostic factors such as ECOG PS, LDH level, and receipt of thoracic RT or PCI. These findings support current treatment algorithms for ESSCLC and provide baseline survival estimates to assess the real-world impact of adding immune checkpoint inhibitors in the future. [ABSTRACT FROM AUTHOR]

The urgent cancer care (UCC) clinic at CancerCare Manitoba (CCMB) opened in 2013 to provide care to individuals diagnosed with cancer and serious blood disorders experiencing complications from the underlying disorder or its treatment. This study examined the impact of the UCC clinic on other health care utilization in Winnipeg, Manitoba, Canada. An interrupted time series study design was used to compare the rates of emergency department (ED) visits, primary care clinician (PCC) visits, and hospitalizations from 1 January 2010 to 31 December 2015. Rates of ED visits were also stratified by ED location, severity, and cancer type. We found a 6% (95% CI 1.00–1.13, p-value = 0.0389) increase in PCC visits, a 7% (95% CI 0.99–1.15, p-value = 0.0737) increase in hospitalizations, a 4% (95% CI 0.86–1.08, p-value = 0.5053) decrease in the rate of ED visits, and a 3% (95% CI 0.92–1.17, p-value = 0.5778) increase in the rate of ED visits during the UCC clinic hours after the UCC clinic opened. The implementation of the UCC clinic had minimal impact on health care utilization. Future work should examine the impact of the UCC clinic on other aspects of healthcare utilization (e.g., number of tests ordered and time spent waiting in CCMB's main clinics) and patient quality of life and patient and health care provider experience. [ABSTRACT FROM AUTHOR]

In 2013, Cancer Care Manitoba (CCMB) launched an urgent cancer care clinic (UCC) to meet the needs of individuals diagnosed with cancer experiencing acute complications of cancer or its treatment. This retrospective cohort study compared the characteristics of individuals diagnosed with cancer that visited the UCC to those who visited an emergency department (ED) and determined predictors of use. Multivariable logistic mixed models were run to predict an individual’s likelihood of visiting the UCC or an ED. Scaled Brier scores were calculated to determine how greatly each predictor impacted UCC or ED use. We found that UCC visits increased up to 4 months after eligibility to visit and then decreased. ED visits were highest immediately after eligibility and then decreased. The median number of hours between triage and discharge was 2 h for UCC visits and 9 h for ED visits. Chemotherapy had the strongest association with UCC visits, whereas ED visits prior to diagnosis had the strongest association with ED visits. Variables related to socioeconomic status were less strongly associated with UCC or ED visits. Future studies would be beneficial to planning service delivery and improving clinical outcomes and patient satisfaction. [ABSTRACT FROM AUTHOR]

We aimed to study the geographic variation in the incidence of COPD. We used health survey data (weighted to the population level) to identify 56,944 cases of COPD in Manitoba, Canada from 2001 to 2010. We used five cluster detection procedures, circular spatial scan statistic (CSS), flexible spatial scan statistic (FSS), Bayesian disease mapping (BYM), maximum likelihood estimation (MLE), and local indicator of spatial association (LISA). Our results showed that there are some regions in southern Manitoba that are potential clusters of COPD cases. The FSS method identified more regions than the CSS and LISA methods and the BYM and MLE methods identified similar regions as potential clusters. Most of the regions identified by the MLE and BYM methods were also identified by the FSS method and most of the regions identified by the CSS method were also identified by most of the other methods. The CSS, FSS and LISA methods identify potential clusters but are not able to control for confounders at the same time. However, the BYM and MLE methods can simultaneously identify potential clusters and control for possible confounders. Overall, we recommend using the BYM and MLE methods for cluster detection in areas with similar population and structure of regions as those in Manitoba. [ABSTRACT FROM AUTHOR]

Context Daily variations in bladder size and position can negatively impact the ability to accurately deliver radiation. Aims We attempted to quantify how bladder volumes and positions change over the course of radiotherapy for muscle invasive bladder cancer and the planning target volume (PTV) margins required to account for such changes. Methods and material Cone-beam computed tomography (CT) images of 28 patients during their first, second, and third fractions and weekly thereafter were acquired. Bladders were contoured and the volume, centre of mass, and the maximal positions were recorded and compared to the planning CT scan. Statistical analysis Bladder parameters were analysed using regression analysis examining for time trends and correlation to the patient, tumour, or treatment-related factors. Results There was great variability in the mean bladder volumes during the radiotherapy courses (154.17 +/- 129.38 cm 3 ). There were no statistically significant trends for volume changes. Deviations in bladder positions were seen but were small in magnitude. No patient factors were identified which could help predict bladder changes clinically. Bladder variability resulted in a high percentage of fractions (39.6%) in which part of the bladder was outside the PTV. Calculated PTV margins (for 90% of the population to receive 95% of the prescription dose) were 1.48 cm right, 1.15 cm left, 2.13 cm posterior, 1.52 cm anterior, 2.23 cm superior, and 0.52 cm inferior. Conclusions Because of random bladder changes, a significant number of fractions were treated in which the clinical target volume (CTV) fell outside of the PTV. Methods to minimize the amount of CTV that is missed on a fraction to fraction basis should be explored., Competing Interests: The authors have declared that no competing interests exist.

Background:  Genitourinary small cell cancer (GUSCC) is a rare malignancy. Most of the published data on how to manage this malignancy is based on institutional experience. We undertook the current retrospective review to determine the outcome of the patients with GUSCC treated at CancerCare Manitoba, Canada over a period of 18 years., Methods: The Manitoba Cancer Registry was used to identify patients with a confirmed pathological diagnosis of small cell cancer (SCC) of the bladder or prostate between January 1, 1995, and October 31, 2013., Results:  There were 42 patients identified, 28 bladder SCC (17 limited, 11 extensive stage) and 14 prostate SCC (one limited, 12 extensive, and one unknown stage). The median age was 70.7 years. There were 22 patients who were treated with chemotherapy and radiation, five received radiation only, four received chemo only, nine did not receive any treatment, one patient had surgery only, and one had surgery and radiation. The median and one-year overall survival for all patients was 10.7 months and 43%. The median and one-year overall survival of SCC of the bladder was 55.1 months and 71% for the limited stage and 10.1 months and 36% for the extensive stage. The median and one-year overall survival for extensive stage SCC of the prostate was 4.1 months and 17%. There was only one patient with limited stage SCC of the prostate who did not receive any treatment and died of progressive disease 11 months from diagnosis., Conclusions:  Our findings suggest that patients with limited stage SCC of the bladder can have a surprisingly good outcome with multimodality treatment. The outcome of the patients with extensive stage SCC of the bladder and prostate remains dismal and optimal therapeutic options have yet to be determined.