BACKGROUND/OBJECTIVES:Cervical cancer outcomes based on geographic location of residence reveal inconsistent patterns, and most of the evidence is from the United States. This retrospective study aimed to investigate whether there existed a difference in overall survival (OS) and recurrence-free survival (RFS) between individuals living within a Canadian city with a tertiary care centre versus those living remotely within a large catchment area (up to >1000 km travel distance), including a sizeable rural component. METHODS:Surgically treated cervical cancer patients from 2000 to 2016 were included. Patients were treated with either radical hysterectomy, trachelectomy, or simple hysterectomy. Adjuvant treatment was provided depending on surgical pathology. OS and RFS were estimated using Kaplan-Meier curves and cumulative incidence curves. RESULTS:Two hundred and eighty-two patients with surgically treated cervical cancer were included: 185 patients living within urban city limits and 97 patients living rurally. There were no significant baseline differences between groups. No significant difference in OS or RFS was found, even after adjusting for death as a competing risk for RFS. The median time to surgery for residents living within versus outside the city was 84 vs. 66 days, respectively, although this difference was not statistically significant (p = 0.3179). CONCLUSIONS:This is the first Canadian study to examine an association between survival and distance to care for cervical cancer.

Abstract:BACKGROUND: Noona is a patient-facing app used by CancerCare Manitoba to connect patients to their electronic health record and communicate with their care team. Since the implementation of Noona, staff have been responsible for registering patients with Noona. Registration rates have been consistently low. With competing clinic priorities and workload demands on front-line staff, an alternative solution was needed. Abstract:OBJECTIVE: The objective of this study was to improve Noona registration amongst cancer patients in Manitoba, Canada. Abstract:MATERIALS: We used the business process management lifecycle approach to explore reasons for low Noona registration and identify strategies to address the issue. The process problem was identified and documented, process models were developed, and semi-structured interviews with 25 front-line staff were conducted. Noona registration was redesigned, tested, and implemented in October 2024. Abstract:RESULTS: Front-line staff had limited time to discuss Noona with patients and register them to use Noona when the patient attended a clinic appointment or for treatment. Staff communication tools and support for patients were limited. Based on the process analysis, a centralized, patient-driven registration process was designed, tested, and implemented. The percentage of new accounts that were patient-activated increased over time. Abstract:CONCLUSION: The patient-driven, centralized process increased the percentage of patient-activated Noona registrations.

e23102 Background: Substance use disorders (SUDs) can adversely affect cancer treatment and survivorship outcomes, including the risk of secondary malignancies among adolescents and young adults (AYAs) with cancer. However, data on the burden of SUDs and associated risk factors in this population remain limited. This study examined the five-year cumulative incidence of SUDs following cancer diagnosis and factors associated with its development among AYAs with cancer. Methods: This retrospective, population-based cohort study used the Manitoba Cancer Registry to identify AYAs aged 15–39 years diagnosed with invasive cancer between 1989 and 2019. Incident SUDs were identified using validated administrative definitions based on one or more hospitalizations or physician visits with diagnoses of alcohol- or drug-related psychoses, dependence, or non-dependent substance abuse (ICD-9 codes 291–305; ICD-10 codes F10–F19, F55, Z50.2, Z50.3). Competing risks regression was used to assess the five-year cumulative incidence of SUDs and the association of age, sex, comorbidities, income, residence, tumor type (sex-specific vs non–sex-specific), calendar year, and receipt of chemotherapy, surgery, or radiation with SUDs. Sex-specific cancers included breast, ovarian, uterine, and cervical cancers in females, and prostate and testicular cancers in males. Results: Among 3,818 AYAs with cancer (mean age at diagnosis, 30.7 years), 2,125 (56%) were female, and 3124 (81%) had solid tumors. The unadjusted 5-year cumulative incidence of SUDs post cancer diagnosis was 4.1% [95% Confidence Interval (CI), 3.5–4.8]. In competing-risk regression analyses, those in the highest income quintile had the lowest risk of developing SUDs compared to those in the lowest income quintile [sub-Hazard ratio (sHR), 0.40; 95% CI 0.25–0.66)] (Table 1). Receipt of chemotherapy (sHR, 1.53; 95% CI 1.07–2.28) and radiation therapy (sHR, 1.60; 95% CI 1.10–2.34) were independently associated with increased SUDs risk, whereas the presence of one or more comorbidities at diagnosis (sHR, 0.62; 95% CI 0.41–0.93) and more recent calendar year of diagnosis (sHR per year, 0.97; 95% CI 0.95–0.99) were associated with reduced risk. Conclusions: SUDs among AYAs with cancer post cancer diagnosis are higher among those in lower income quintiles and those receiving chemotherapy or radiation therapy. These findings support the integration of early, targeted substance use screening and equity-informed interventions into routine AYA oncology care for patients undergoing intensive treatment and those from socioeconomically disadvantaged backgrounds. Five-year adjusted cumulative incidence of substance use disorders by income quintile. Income Quintile 5-Year Adjusted Cumulative Incidence (%) Q1 (lowest income) 6.3 Q2 3.4 Q3 3.6 Q4 2.0 Q5 (highest income) 2.7

INTRODUCTION:Colorectal cancer (CRC) incidence is increasing among younger individuals in many countries. We examined CRC incidence and mortality by age group, site, and histology in Canada. METHODS:Data from the Canadian Cancer Registry and the Canadian Vital Statistics Death Database were used to determine CRC incidence from 1992 to 2019 and mortality from 1974 to 2022. We calculated incidence by age group, site, and histology and mortality by age group and site. Annual percent change was calculated using Joinpoint Regression. Age-period-cohort models with splines were run to indicate influence on CRC incidence. RESULTS:CRC incidence was stable for individuals 20-29 years, increased for those 30-49, remained stable for 50-54, and decreased for 55 years and older. Proximal, distal, and rectal cancer incidence was stable or increased for individuals less than 55 and decreased for those over 55. Adenocarcinoma CRCs increased for those less than 55. Mucinous and signet ring cell CRCs decreased or remained stable for all ages. Neuroendocrine CRCs increased for most ages. Age, cohort, and period effects are evident. CRC mortality stopped decreasing in the late 1990s for individuals 20-49 but decreased for those over 50. Proximal and distal CRC mortality decreased for all ages. Rectal cancer mortality increased. DISCUSSION:CRC incidence and mortality in Canada vary by age, site, and histology. In addition to a reduction in the screening start age, CRC screening programs must focus on individuals 50-54 years of age because they have not experienced a decrease in CRC incidence.

We examined the association between the COVID-19 pandemic and screening, treatment, and overall survival for individuals diagnosed with breast cancer in Manitoba, Canada. We used population-based data and a quasi-experimental study with an interrupted time series analysis to examine the number of screening mammograms, first treatment rates, and 2-year overall survival prior to and after COVID-19 for individuals diagnosed with breast cancer. There was a significant decrease in screening mammograms 2 years after the start of the pandemic (ratio = 0.73

e22658 Background: While increased risk of colorectal cancer (CRC) is well established in individuals with Lynch syndrome (LS), North American population-based data on extracolonic cancers (ECCs), especially with some gene variants, remains limited. Better understanding of ECCs in LS may improve screening, care and outcomes. Manitoba has a provincial registry of individuals with mismatch repair (MMR) germline pathogenic variants (GPVs), and a multidisciplinary clinic for individuals with LS, focused on screening, surveillance and risk-reduction strategies. The aims of this study are: (1) characterize ECCs in LS; (2) evaluate impact of clinic practices on individuals with LS. Methods: We conducted a retrospective cohort study of individuals with GPVs enrolled in the Manitoba LS registry between 1999 and 2023. Clinical and pathological data were obtained from provincial cancer and genetics databases. Outcomes included ECC type, age at diagnosis, stage, tumor MMR/MSI testing, mode of cancer detection, enrollment in LS clinic and associated screening/surveillance tests. Descriptive statistics were used. Results: 124 individuals with GPVs had 192 ECCs. Impacted GPVs were: 28.1% MLH1, 27.4% MSH2, 23.4% MSH6, 17.7% PMS2, 3.2% EPCAM. Mean age of diagnosis was 57 (SD 12.6). Common cancers were: endometrial (34.9%), genitourinary tract (8.9%) ovarian (6.3%), small bowel/stomach (5.7%), sebaceous (4.2%), hepatobiliary (2.6%). Fifty (40%) individuals had >2 ECC diagnoses. The majority of ECCs were diagnosed following symptomatic presentation (56.8%) and 8.7% were advanced or metastatic stage at diagnosis. 68 (35.4%) ECCs had tumor MMR or MSI testing and 6 (3.1%) received immunotherapy. Among individuals with ECCs, 66.1% were followed in the LS clinic. Clinic-followed individuals had higher uptake of ECC screening than those not followed (89.0% vs 66.7%), although few tests were associated with a cancer diagnosis (12%). Conclusions: While ECCs in LS are less common than CRC, they are clinically significant, particularly when of advanced stage or if limited treatment options exist. In our cohort, tumour MMR/MSI testing and receipt of immunotherapy was low, highlighting areas for improvement. Higher screening uptake among clinic-followed individuals may support a centralized care model. This underscores the need for prospective studies to optimize ECC screening and evaluate outcomes.

e24120 Background: Adolescents and young adults (AYAs) with cancer have unique medical and psychosocial needs. Despite improvements in survival outcomes, AYAs remain at elevated risk for psychological morbidity. Sex-based differences in the development of mood and anxiety disorders are not well characterized. This study examined factors associated with the development of mood and anxiety disorders among AYAs within five years of cancer diagnosis stratified by sex and tumor type. Methods: This retrospective cohort study used population-based data from the Manitoba Cancer Registry to identify individuals aged 15–39 years diagnosed with invasive cancer between 1989 and 2019. Mood and anxiety disorders were determined using validated administrative algorithms. Associations between demographic, clinical, and treatment-related factors including age at diagnosis, comorbidities, income quintile, residence, year of diagnosis, sex and tumor type (sex-specific, non-sex-specific solid, and non-solid), and receipt of chemotherapy, surgery, and radiation were evaluated using competing risks regression. Sex-specific cancers included breast, ovarian, uterine, and cervical cancers in females, and prostate and testicular cancers in males. Results: Among 3,818 AYAs with cancer, 56% were female, and 21% were aged 15-25. Most individuals had solid tumors (83%), of whom 34% had a sex-specific tumor. In competing risks regression, compared to males with a sex-specific cancer, females with sex-specific cancers [sub-Hazard Ratio (sHR) 2.28, 95% Confidence Interval (CI) 1.36–3.82], females with non–sex-specific solid tumors (sHR 2.22, 95% CI 1.33–3.70), females with non-solid tumors (sHR 2.98, 95%CI 1.55–5.71), and males with non-solid tumors (sHR 1.97, 95% CI 1.03–3.78) had a higher risk of developing mood or anxiety disorder. Additionally, younger age at diagnosis (Table 1), presence of one or more comorbidities (sHR 1.34, 95% CI 1.05-1.71), a more recent year of cancer diagnosis (sHR 1.03 per year, 95% CI 1.01-1.04), receipt of chemotherapy (sHR 1.38, 95% CI 1.03-1.84) and surgery (sHR 1.93, 95% CI 1.38-2.69) were associated with an increased risk of mood and anxiety disorders. Conclusions: Among AYAs with cancer, the risk of mood and anxiety disorders was highest among females, those with non-solid tumors, a younger age at diagnosis, presence of a comorbidity, a more recent diagnosis year, and receipt of chemotherapy or surgery. These findings underscore the need for targeted mental health screening and psychosocial support for AYA populations at a higher risk of a mood or anxiety disorder. 5-year adjusted cumulative incidence of mood and anxiety disorders post cancer diagnosis. Age at diagnosis (years) 5-year adjusted cumulative incidence (%) 15 14.0 20 10.2 25 7.9 30 7.0 35 7.2 39 7.6

Genetic predisposition to hereditary breast and ovarian cancer and Lynch syndrome increases the risk of developing cancer, including epithelial ovarian cancer (EOC). Depending on the pathogenic variant, (e.g., BRCA1 or PMS2) the risk of developing EOC ranges from approximately 3%-60%. To reduce this risk, many individuals are offered risk-reducing salpingo-oophorectomy (RRSO), a procedure in which fallopian tubes and ovaries are removed. Some centers have dedicated programs that provide targeted care for individuals at risk of gynecologic cancers, such as the Hereditary Gynecology Clinic in Winnipeg, Manitoba. To better understand how individuals across a spectrum of risk values for developing EOC interpret their personal risk and make decisions regarding RRSO, we conducted a convergent mixed-methods study involving an online survey and virtual interview. Sixty-three surveys and twenty interviews were completed. Participants viewed objective risk information as a starting point, to which 'experiential knowledge' and perceived control were applied and integrated into their personal subjective risk assessment. Perceived risk was intertwined with cancer worry, and individuals made decisions regarding RRSO based on factors such as perceived risk, control, family planning, hormonal impacts, and recovery. Importantly, healthcare providers exerted both direct and indirect influences on the decision-making process.

The timely diagnosis of tumor progression is crucial to implementing treatment changes that can improve patient survival. In this study, we analyzed scans from 114 patients with glioblastoma multiforme to differentiate between pseudoprogression and true tumor progression. We used processed skull segmented and augmented data to perform transfer learning using a pre-trained, customized ResNet-18. An AUC of 0.71, an F1 score of 0.64, and a geometric mean of sensitivity and specificity of 0.67 were achieved. Although the saliency maps demonstrate that the model was able to identify the correct region of interest, the low scaled Brier score of 0.07 indicates that the model is just slightly better than random, underscoring the importance of outcome likelihood metrics. These results demonstrate that the achieved performance levels are not yet sufficient to support reliable clinical decision-making. To make the model clinically applicable, further investigation and refinement are required to enhance its accuracy, reliability, and overall clinical utility.

Glioblastoma multiforme (GBM) are extremely invasive cancers. The treatment of GBM involves microsurgical resection followed by radiochemotherapy and chemotherapy. As a response to radiation treatment, in many cases, a new or a progressing lesion is observed in imaging studies which resolves without additional treatment. This phenomenon is called pseudoprogression (PsP). In contrast to PsP, a True Progression (TP) represents an enlarging lesion that requires a change in the treatment. Distinguishing between PsP and TP is thus central to treatment choice and clinical management. However, both types of progression present themselves with overlapping characteristics in imaging as assessed by radiologists. An automated machine learning method that can learn to discover distinctive markers to reliably differentiate between the two situations will thus be an effective prognostic tool in the clinical management of GBM. In this paper we present a 3D convolutional neural network (CNN) trained on 3D MRI images from 114 GBM patients to classify PsP and TP. Using a 5-fold cross validation strategy, we report multiple metrics by evaluating the model performance on left-out MRI image volumes not used during training. Specifically, our trained model performs with: AUCROC: 0.74, Peak geometric mean of specificity and sensitivity: 0.69, Brier Score: 0.22, Scaled Brier Score: 0.04. We also present decision curve analysis for our model. Prior works on this topic have reported only AUCROC. For model interpretability, we have used the technique GradCAM to discover and visualize the most salient regions in the MRI volume that are used by the CNN for making the decision. Our results show the neural network paying more attention to the lesion and peri-tumoral regions. These findings suggest further investigation of deep learning models trained on larger imaging datasets to build more robust and generalizable models for distinguishing between PsP and TP.

Background: Delays in treatment can lead to increases in cancer morbidity and mortality. There were many concerns that the COVID-19 pandemic led to delays in cancer treatment. Several studies have examined this issue but with serious limitations. We conducted a study that addressed many of these limitations and evaluated changes in first treatment, surgery, systemic therapy, and radiation therapy (RT) during the pandemic for individuals diagnosed with cancer in Manitoba, Canada. Methods: A population-based, quasi-experimental cross-sectional study with an interrupted time series analysis was used to examine time to first treatment (expressed as treatment rates accounting for the competing risk of death) before (January 2015-September 2019) and after (April 2020-December 2022) the COVID-19 pandemic. Results: When compared to the counterfactual scenario without COVID-19, first treatments were not received significantly later during the COVID-19 period for any cancer site. Individuals diagnosed with breast, colon, endocrine, or head and neck cancer had their first treatment within 90 days of diagnosis significantly sooner when comparing the COVID-19 period to the counterfactual. When examining type of treatment within one year of diagnosis, individuals diagnosed with breast cancer had surgery significantly later from April to June 2020 and systemic therapy significantly sooner from April 2020 to September 2021. Individuals diagnosed with colon cancer had surgery significantly sooner from April 2020 to June 2021 and individuals diagnosed with rectal cancer had RT significantly later from January to June 2021. Conclusions: Although significantly impacted by COVID-19, the cancer care system in Manitoba was able to prioritize individuals diagnosed with cancer and modify treatment modalities resulting in no significant delays in first treatment between April 2020 and December 2022. Policy summary: It will be important to assess long-term survival and if unaltered, the ongoing use of strategies first used in the pandemic might be justified.

BACKGROUND:Cancer progression is an important outcome in cancer research. However, it is frequently documented only in electronic health records (EHRs) as unstructured text, which requires lengthy and costly chart reviews to extract for retrospective studies. OBJECTIVE:This study aimed to evaluate the performance of 3 deep learning language models in determining breast and colorectal cancer progression in EHRs. METHODS:EHRs for individuals diagnosed with stage 4 breast or colorectal cancer between 2004 and 2020 in Manitoba, Canada, were extracted. A chart review was conducted to identify cancer progression in each EHR. Data were analyzed with pretrained deep learning language models (Bio+ClinicalBERT, Clinical-BigBird, and Clinical-Longformer). Sensitivity, positive predictive value, area under the curve, and scaled Brier scores were used to evaluate performance. Influential tokens were identified by removing and adding tokens to EHRs and examining changes in predicted probabilities. RESULTS:Clinical-BigBird and Clinical-Longformer models for breast and colorectal cancer cohorts demonstrated higher accuracy than the Bio+ClinicalBERT models (scaled Brier scores for breast cancer models: 0.70-0.79 vs 0.49-0.71; scaled Brier scores for colorectal cancer models: 0.61-0.65 vs 0.49-0.61). The same models also demonstrated higher sensitivity (breast cancer models: 86.6%-94.3% vs 76.6%-87.1%; colorectal cancer models: 73.1%-78.9% vs 62.8%-77.0%) and positive predictive value (breast cancer models: 77.9%-92.3% vs 80.6%-85.5%; colorectal cancer models: 81.6%-86.3% vs 72.9%-82.9%) compared to Bio+ClinicalBERT models. All models could remove more than 84% of charts from the chart review process. The most influential token was the word progression, which was influenced by the presence of other tokens and its position within an EHR. CONCLUSIONS:The deep learning language models could help identify breast and colorectal cancer progression in EHRs and remove most charts from the chart review process. A limited number of tokens may influence model predictions. Improvements in model performance could be obtained by increasing the training dataset size and analyzing EHRs at the sentence level rather than at the EHR level.

PURPOSEThis study examined the association between COVID-19 and cancer incidence by sex in Manitoba, Canada.METHODSWe used a population-based quasi-experimental study design and an interrupted time-series analysis to compare the rate of new cancer diagnoses between males and females before (January 2015 until December 2019) and after the start of the COVID-19 pandemic (April 2020 until December 2022).RESULTSA total of 16,200 females and 20,631 males diagnosed with cancer between 2015 and 2022 in Manitoba were included. Colon cancer incidence decreased by 34% for males and females from April to September 2020. Incidence then remained stable for males but decreased by 22% from October 2021 to December 2022 for females. Brain and CNS cancer incidence decreased by 37% for males during 2021 and 2022 but only for females during the last quarter of 2020 and the first quarter of 2021 (77%). Urinary cancer decreased by 18% for males from April 2020 to December 2022 but was stable for females. Head and neck cancers decreased by 22% for males during 2020, but was stable for females. As of December 2022, the largest estimated cumulative differences in the number of cases occurred for males diagnosed with brain and CNS cancer (31.6% deficit for males, 76 cases), urinary cancer (18.4% deficit, 186 cases), and endocrine cancer (52.4% surplus, 56 cases), and females diagnosed with colon cancer (19.7% deficit, 187 cases).CONCLUSIONSex-based differences in the association between age-standardized cancer incidence and the COVID-19 pandemic exist for several cancer sites. Sex-based differences on postpandemic cancer incidence, especially for brain, CNS, urinary, and colon cancers, need follow-up because of the ongoing deficits documented in this study.

e23103 Background: Disruptions to health care during the COVID-19 pandemic raises the possibility of delays in treatment for individuals diagnosed with cancer. It is critical that we evaluate the association between the COVID-19 pandemic and time-to-first treatment (TTFT) to address public and patient anxiety, inform recovery efforts, and identify strategies to reduce the cancer system’s vulnerability to future disruptions. Objective: To examine the association between the COVID-19 pandemic and time from cancer diagnosis to first treatment in Manitoba, Canada. Methods: A retrospective, population-based, quasi-experimental study that included individuals diagnosed with breast, colon, rectal, hematologic, lung, or prostate cancer between January 2015 and December 2021 was performed. Interrupted time series analyses with competing risk models were used to compare TTFT for those diagnosed before and after the start of the pandemic. Time-to-first treatment was calculated from diagnosis date to first treatment date (i.e., chemotherapy, hormone therapy, immunotherapy, radiotherapy, or surgery). Death without treatment was included as a competing risk. Follow-up time was censored at three months post-diagnosis. Sub-hazard ratios (SHR) and 95% confidence intervals (CI) were reported. Higher SHR indicates earlier treatment. The delta restricted mean time-to-treatment (D_RMTT) at three months was calculated to complement SHR values, where negative times indicate earlier treatment. Since observation is standard of care for low-risk prostate cancer and androgen deprivation therapy was widely used to temporize intermediate and high-risk prostate cancer patients, analyses were restricted to stage IV prostate cancer. Results: Time-to-first treatment was shorter for individuals diagnosed with breast cancer during the COVID-19 pandemic period (SHR: 1.40; 95% CI 1.24-1.57; D_RMTT: -6.6 days). Time-to-first treatment was also shorter for individuals diagnosed with colon cancer from April 2020 to June 2021 (SHR: 1.25; 95% CI 1.09-1.42; D_RMTT: -6.5 days) but not from July 2021 to December 2021 (SHR: 0.96; 95% CI 0.81-1.15; D_RMTT: 1.2 days). All other analyses did not demonstrate a statistically significant change in TTFT: rectal cancer (SHR: 1.00; 95% CI: 0.83-1.21; D_RMTT: 0.0 days), hematological cancers (SHR: 0.87; 95% CI: 0.74-1.01; D_RMTT:3.9 days); lung cancer (SHR: 1.09; 95% CI: 0.97-1.23; D_RMTT: -2.3 days); and stage IV prostate cancer (SHR: 1.15; 95% CI: 0.89-1.49; D_RMTT: -4.1 days). Conclusions: The COVID-19 pandemic has not increased the time from diagnosis date to first treatment date for individuals diagnosed with breast, colon, rectal, hematologic, lung, or stage IV prostate cancer in Manitoba, Canada.

OBJECTIVE:To determine if anaemia and blood transfusions in the perioperative, chemotherapy and radiation treatment periods are associated with overall survival (OS) and recurrence-free survival (RFS) in high-grade endometrial cancer. METHODS:This retrospective cohort study examined patients at a single centre treated for high-grade endometrial cancer (2010-2023). This included International Federation of Gynecology and Obstetrics (FIGO) grade 3 endometrioid, serous, carcinosarcoma, mixed, clear cell, mucinous, dedifferentiated and undifferentiated histology. Primary outcomes were OS and RFS. Predictor variables were nadir haemoglobin and transfusion status. Multivariable Cox regression models for OS and RFS analysed the associations of treatment period-specific anaemia, overall transfusion status and confounder variables. RESULTS:Two hundred twenty-seven cases were included; 64-86% of patients were anaemic during any treatment, with 0-10% having severe anaemia. Twenty-two patients (9.7%) had at least one blood transfusion. Transfusion in the perioperative and chemotherapy periods was associated with poorer survival, significant only for shorter RFS in the chemotherapy cohort (HR 3.22, p=0.04). There was no association between anaemia and survival. CONCLUSION:This study is among the first to assess anaemia in treated patients with high-grade endometrial cancer and the associations of anaemia and blood transfusion with survival outcomes. Further larger studies are needed to strengthen evidence and guide transfusion policies.

PURPOSE To compare the cumulative incidence of mental disorders among adolescents and young adults (AYAs) diagnosed with cancer with the general population and their unaffected siblings. METHODS A retrospective, population-based, matched cohort design was used to investigate the impact of cancer diagnosis on mental disorders among individuals age 15-39 diagnosed between 1989 and 2019. Two cancer-free cohorts were identified: matched population-based and sibling cohorts. Outcomes included incidence of mood and anxiety disorders, substance use disorders, suicide outcomes, psychotic disorders, and any of the preceding four categories within 5 years of cancer diagnosis. Competing risk regression was used to estimate adjusted subhazard ratios (aSHR) and 95% CIs. RESULTS Among 3,818 AYAs with cancer matched to the population-based cancer-free cohort, individuals with cancer were more likely to be diagnosed with incident mental disorders than those without cancer; the risk was highest immediately after a cancer diagnosis and decreased over time with aSHR [95% CI] for mood and anxiety disorders at 0-6 months (11.27 [95% CI, 6.69 to 18.97]), 6-12 months (2.35 [95% CI, 1.54 to 3.58]), and 12-24 months (2.06 [95% CI, 1.55 to 2.75]); for substance use disorders at 0-6 months (2.73 [95% CI, 1.90 to 3.92]); for psychotic disorders at 0-6 months (4.69 [95% CI, 2.07 to 10.65]); and for any mental disorder at 0-6 months (4.46 [95% CI, 3.41 to 5.85]), 6-12 months (1.56 [95% CI, 1.14 to 2.14]), and 12-24 months (1.7 [95% CI, 1.36 to 2.13]) postcancer diagnosis. In sibling comparison, cancer diagnosis was associated with a higher incidence of mood and anxiety and any mental disorder during first 6 months of cancer diagnosis. CONCLUSION AYAs with cancer experience a greater incidence of mental disorders after cancer diagnosis relative to population-based and sibling cohorts without cancer, primarily within first 2 years, underscoring the need to address mental health concerns during this period.

The interaction of myeloid-derived suppressor cells (MDSCs) with T cells within G-CSF-mobilized peripheral blood stem cell (PBSC) grafts in patients undergoing autologous or allogeneic hematopoietic stem cell transplantation remains to be elucidated. Through studying allo- and auto-PBSC grafts, we observed grafts containing large numbers of T cells and MDSCs with intergraft variability in their percentage and number. T cells from autologous grafts compared to allografts expressed relative higher percentages of inhibitory receptors PD-1, CTLA-4, TIM-3, LAG-3, TIGIT and BTLA. Autograft T cells had decreased cell proliferation and IFN-γ secretion, which supported the possible presence of T cell exhaustion. On the contrary, graft monocytic MDSCs (M-MDSCs) expressed multiple inhibitory receptor ligands, including PD-L1, CD86, Galectin-9, HVEM and CD155. The expression of inhibitory receptor ligands on M-MDSCs was correlated with their corresponding inhibitory receptors on T cells in the grafts. Isolated M-MDSCs had the ability to suppress T cell proliferation and IFN-γ secretion and/or promote Treg expansion. Blocking the PD-L1-PD-1 signaling pathway partially reversed the functions of M-MDSCs. Taken together, our data indicated that T cells and M-MDSCs in PBSC grafts express complementary inhibitory receptor–ligand pairing, which may impact the quality of immune recovery and clinical outcome post transplantation.

BACKGROUND:In Canada, individuals with gynecologic reproductive organs (ovaries, fallopian tubes, uterus) over the age of 70 comprise a large proportion of epithelial ovarian cancer patients. These patients often have co-morbidities, polypharmacy, or decreased functional status that may impact treatment initiation and tolerance. Despite this, there is limited evidence to guide treatment for older patients diagnosed with ovarian epithelial carcinoma.METHODS:This is a retrospective study with data from Manitoba, Canada. The data were obtained from the Manitoba Ovarian Cancer Database, the Manitoba Cancer Registry, and electronic health records. All individuals with epithelial ovarian, fallopian tube, or peritoneal cancer diagnosed between 2009 and 2018 were identified. Patients aged > 70 at the time of diagnosis were included in the study cohort.RESULTS:Four hundred and forty individuals were included. The majority had advanced stage disease (56%). Moreover, 59% of patients received no chemotherapy. Of the patients who received chemotherapy, 20% received <2 cycles and 21% required a dose reduction due to toxicity. Univariable and multivariable analysis identified advanced stage (p < 0.001), treatment modality (p < 0.001), and advanced age at diagnosis (p < 0.001) with poorer overall survival.CONCLUSIONS:Our study demonstrated a high rate of chemotherapy dose reduction and discontinuation in the elderly epithelial ovarian cancer population. Further research is needed to identify risk factors for treatment discontinuation and intolerance in this population.

BACKGROUND & AIMS: We describe the experience of Lynch syndrome (LS) diagnosis in the province of Manitoba, Canada, over the past 20 years. METHODS: We performed a retrospective review of charts from the provincial Genetics Clinic from January 1, 2000, to May 31, 2023. We extracted data on individuals identified to carry a germline pathogenic or likely pathogenic LS gene variant, the mode of ascertainment, family history, and cascade genetic testing (CGT). Data were stratified and compared before and after the year of implementation (October 2013) of the provincial LS screening program (LSSP) and ascertainment by the LSSP vs clinic referrals (CRs). RESULTS: Between 2014 and 2021, 50 of 101 (49.5%) index cases were identified by the LSSP compared with 51 of 101 (50.5%) from CRs. The proportion of PMS2 variants was 34% (17 of 50) for LSSP index cases compared with 21.6% (11 of 51) for CRs from 2014 to 2021 (P < .001). Among CRs from 2014 to 2021, 24 of 51 (47.1%) families met the Amsterdam criteria, compared with 11 of 50 (22.0%) for the LSSP (P = .01). CGT occurred among 46.8% (95 of 203; average, 1.9 relatives/index) of first-degree relatives of CR index cases vs 36.5% (84 of 230; average, 1.7 relatives/index) of first-degree relatives of LSSP index cases (P = .03). Daughters were most likely to undergo CGT. CONCLUSIONS: A tumor screening program is more effective at detecting individuals with lower penetrant gene variants and families who do not meet traditional family history-based criteria. Cascade genetic testing is higher among clinic referrals compared with the screening program. These findings suggest a complementary role of these 2 ascertainment methods for Lynch syndrome.