Princess Margaret Cancer Centre Research Articles

Single organ metastatic sites in non-small cell lung cancer: Patient characteristics, treatment patterns and outcomes from a large retrospective Canadian cohort

BackgroundThere is a paucity of information about the characteristics, treatment patterns, and outcomes of non-small cell lung cancer (NSCLC) patients with single organ metastasis (SOM). MethodsThis retrospective cohort study includes all patients with a diagnosis of stage IV NSCLC diagnosed from 2014 to 2016 and treated at Princess Margaret Cancer Centre. We compared baseline characteristics and patterns of metastatic sites between patients with SOM versus multiple (M)OM. Additionally, we identified treatment modalities and outcomes for patients with SOM. Cox multivariable models (MVA) were utilized to evaluate differences in overall survival (OS) between the SOM and MOM cohorts. ResultsOf 893 pts analyzed, 457 (51 %) had SOM, while 436 (49 %) had MOM at initial diagnosis. Demographics were comparable between the two groups. Brain was the most common site of metastasis for SOM patients. When compared to the MOM group, the SOM group had lower percentages of liver and adrenal metastases. Amongst SOM patients, 54 % received single modality treatment, and 20 % did not receive any treatment for their SOM. In MVA, patients with liver (HR 2.4), bone (HR 1.8), and pleural (HR 1.7) metastasis as their SOM site had the worst outcomes, with median OS of 6.8 months, 12.1 months, and 13.0 months respectively. Patients with SOM had a significantly improved median OS compared to those with MOM (15.9 months vs. 10.6 months; HR 0.56, 95 % CI 0.47–0.66, p < 0.001). ConclusionIn NSCLC patients who presented with SOM, survival correlated with the initial organ involved and was better overall compared to patients with MOM. SOM NSCLC may benefit from specific management strategies and SOM patients could be considered as a specific subgroup for survival analyses in observational and non-randomized interventional studies. In clinical trials, SOM can be considered as a stratification factor in the future.

KRAS Allelic Variants in Biliary Tract Cancers

Biliary tract cancers (BTCs) contain several actionable molecular alterations, including FGFR2, IDH1, ERBB2 (formerly HER2), and KRAS. KRAS allelic variants are found in 20% to 30% of BTCs, and multiple KRAS inhibitors are currently under clinical investigation. To describe the genomic landscape, co-sequence variations, immunophenotype, genomic ancestry, and survival outcomes of KRAS-mutated BTCs and to calculate the median overall survival (mOS) for the most common allelic variants. This retrospective, multicenter, pooled cohort study obtained clinical and next-generation sequencing data from multiple databases between January 1, 2017, and December 31, 2022. These databases included Princess Margaret Cancer Centre, MD Anderson Cancer Center, Foundation Medicine, American Association for Cancer Research Project GENIE, and cBioPortal for Cancer Genomics. The cohort comprised patients with BTCs who underwent genomic testing. The main outcome was mOS, defined as date of diagnosis to date of death, which was measured in months. A total of 7457 patients (n = 3773 males [50.6%]; mean [SD] age, 63 [5] years) with BTCs and genomic testing were included. Of these patients, 5813 had clinical outcome data available, in whom 1000 KRAS-mutated BTCs were identified. KRAS allelic variants were highly prevalent in perihilar cholangiocarcinoma (28.6%) and extrahepatic cholangiocarcinoma (36.1%). Thirty-six KRAS allelic variants were identified, and the prevalence rates in descending order were G12D (41%), G12V (23%), and Q61H (8%). The variant G12D had the highest mOS of 25.1 (95% CI, 22.0-33.0) months compared with 22.8 (95% CI, 19.6-31.4) months for Q61H and 17.8 (95% CI, 16.3-23.1) months for G12V variants. The majority of KRAS-mutated BTCs (98.9%) were not microsatellite instability-high and had low tumor mutational burden (ranging from a median [IQR] of 1.2 (1.2-2.5) to a mean [SD] of 3.3 [1.3]). Immune profiling through RNA sequencing of KRAS and NRAS-mutated samples showed a pattern toward a more immune-inflamed microenvironment with higher M1 macrophage activation (0.16 vs 0.12; P = .047) and interferon-γ expression compared with wild-type tumors. The G12D variant remained the most common KRAS allelic variant in all patient ancestries. Patients with admixed American ancestry had the highest proportion of G12D variant (45.0%). This cohort study found that KRAS allelic variants were relatively common and may be potentially actionable genomic alterations in patients with BTCs, especially perihilar cholangiocarcinoma and extrahepatic cholangiocarcinoma. The findings add to the growing data on genomic and immune landscapes of KRAS allelic variants in BTCs and are potentially of value to the planning of specific therapies for this heterogeneous patient group.

Impact of an Inter-Professional Clinic on Pancreatic Cancer Outcomes: A Retrospective Cohort Study.

Background: Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges in diagnosis, staging, and appropriate treatment. Furthermore, patients with PDAC often experience complex symptomatology and psychosocial implications that require multi-disciplinary and inter-professional supportive care management from health professionals. Despite these hurdles, the implementation of inter-professional clinic approaches showed promise in enhancing clinical outcomes. To assess the effectiveness of such an approach, we examined the impact of the Wallace McCain Centre for Pancreatic Cancer (WMCPC), an inter-professional clinic for patients with PDAC at the Princess Margaret Cancer Centre (PM). Methods: This retrospective cohort study included all patients diagnosed with PDAC who were seen at the PM before (July 2012-June 2014) and after (July 2014-June 2016) the establishment of the WMCPC. Standard therapies such as surgery, chemotherapy, and radiation therapy remained consistent across both time periods. The cohorts were compared in terms of survival rates, disease stage, referral patterns, time to treatment, symptoms, and the proportion of patients assessed and supported by nursing and allied health professionals. Results: A total of 993 patients were included in the review, comprising 482 patients pre-WMCPC and 511 patients post-WMCPC. In the multivariate analysis, adjusting for ECOG (Eastern Cooperative Oncology Group) and stage, it was found that post-WMCPC patients experienced longer median overall survival (mOS, HR 0.84, 95% CI 0.72-0.98, p = 0.023). Furthermore, the time from referral to initial consultation date decreased significantly from 13.4 to 8.8 days in the post-WMCPC cohort (p < 0.001), along with a reduction in the time from the first clinic appointment to biopsy (14 vs. 8 days, p = 0.022). Additionally, patient-reported well-being scores showed improvement in the post-WMCPC cohort (p = 0.02), and these patients were more frequently attended to by nursing and allied health professionals (p < 0.001). Conclusions: The implementation of an inter-professional clinic for patients diagnosed with PDAC led to improvements in overall survival, patient-reported well-being, time to initial assessment visit and pathological diagnosis, and symptom management. These findings advocate for the adoption of an inter-professional clinic model in the treatment of patients with PDAC.

Abstract PO4-04-09: Incidence, prevalence, risk factors, and impact of fatty liver disease in metastatic HR+/HER2− breast cancer patients treated with Endocrine Therapy and CDK 4/6 Inhibitor

Abstract Background: In patients with early-stage breast cancer (BC), non-alcoholic fatty liver disease (NAFLD) is associated with increased recurrence, cardiovascular events, and non-cancer death. Endocrine therapy increases the risk of NAFLD. The impact of cyclin-dependent kinases 4/6 inhibitors (CDKi) combined with endocrine therapy on NAFLD and prognostic association in metastatic breast canceris unknown. Here, we characterize the incidence, prevalence, risk factors, and treatment outcomes of NAFLD in women with metastatic HR+/HER2- BC. Methods: We conducted a retrospective cohort study of patients with advanced HR+/HER2- BC receiving first line endocrine and CDKi at Princess Margaret Cancer Centre, Toronto, Canada between January 2018 – June 2022. Patients were excluded if they had liver disease, prior chemotherapy, or no access to CT scans. Demographic, treatment, toxicity, and survival data were extracted. Liver Attenuation Index (LAI) on contrast-enhanced portal venous phase CT scan was utilized.NAFLD was defined as LAI &amp;gt;25 HU. Univariable binary-logistic regression analysis wasused to assess independent predictive factors of NAFLD. Statistical significance was defined as p&amp;lt; 0.05. Quantitative significance was defined by the Burnand criteria. Time to treatment failure (TTF) was assessed using Cox proportional hazards modeling. Results: Of approximately 90 eligible patients, 40 are included in this analysis. Baseline demographics included median age 61 years, 72% post-menopausal, 58% de-novo metastatic disease, and 27% visceral disease. Of 40 patients, 28 (70%) had NAFLD at anytime (12 at baseline and 16 incident). Associations with NAFLD are shown in Table 1. Presence of NAFLD was associated quantitatively but not statistically with age &amp;gt; 65 (OR 2.6), post-menopausal status (OR 2.6), and inversely associated with prior chemotherapy (OR 0.27) and visceral disease (OR 0.38). Lack of NAFLD at any time was significantly associated with worse TTF (mean TTF 497 versus 1228 days, HR=4.28, 95% CI: 1.89-9.68, p&amp;lt; 0.001). Patients without NAFLD at baseline also had a worse TTF (mean 903 vs 1186 days) compared to those with it at baseline, but this difference was not statistically significance (HR=1.93, 95%CI: 0.77-4.83, p= 0.163). No significant differences were found in grade 3/4 adverse events. Patients who have presented NAFLD at any time received an average of 1.36 subsequent lines of therapy compared to 2.08 in those without. Discussion &amp; Conclusion: This analysis demonstrated an association between presence of NAFLD and longer TTF. This may reflect reverse causation whereby longer exposure to ET and CDKi increases the observation of NAFLD or that these are distinct populations with different molecular pathways leading to differences in response to treatment and prognosis. It is noteworthy that the median time to develop NAFLD in the incident group was 339 days, and the group that never developed NAFLD was on treatment longer than this. Overexpression of CDK 4/6 pathway, could increase sensitivity and duration to treatment with CDKi but produce adverse metabolic changes of increased lipid synthesis, as described in pre-clinical models. If this hypothesis is confirmed, synergistically addressing these metabolic changes with physical exercise, dietary, or pharmacological interventions may improve these patients’ fitness for subsequent lines of therapy. Table 1 Citation Format: Diego Malon Gimenez, Consolacion Molto Valiente, Shopnil Prasla, Danielle Cuthbert, Abhenil Mittal, Faris Tamimi, Massimo Di Iorio, Meredith Li, Neha Pathak, Eitan Amir, Kartik Jhaveri, Michelle Nadler. Incidence, prevalence, risk factors, and impact of fatty liver disease in metastatic HR+/HER2− breast cancer patients treated with Endocrine Therapy and CDK 4/6 Inhibitor [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-04-09.

Abstract 1249: cBioPortal for Cancer Genomics

Abstract cBioPortal for Cancer Genomics is an open-source platform for interactive, exploratory analysis of large-scale clinico-genomic data. cBioPortal provides a suite of user-friendly visualizations and analyses, including OncoPrints, mutation lollipop plots, variant interpretation, group comparison, survival analysis, expression correlation analysis, alteration enrichment analysis, cohort and patient-level visualization. The public site (https://www.cbioportal.org) is accessed by &amp;gt;35,000 unique visitors each month and hosts data from &amp;gt;390 studies spanning individual labs and large consortia. All data is available in the cBioPortal Datahub: https://github.com/cBioPortal/datahub; in 2023 we added 35 studies (~16,000 samples). In addition, &amp;gt;86 instances of cBioPortal are installed at academic institutions and companies worldwide. We also host a dedicated instance for AACR Project GENIE, enabling access to the GENIE cohort of &amp;gt;197,000 clinically sequenced samples from 19 institutions (https://genie.cbioportal.org). The GENIE Biopharma Collaborative (BPC) enables the collection of comprehensive clinical annotations including response, outcome, and treatment history, which can all be visualized in cBioPortal. BPC cohorts for non-small cell lung cancer (~2,000 samples) and colorectal cancer (~1,500 samples) are available, with more cancer types to come. This past year, we significantly enhanced existing features. Group comparison now includes a Mutations tab showing a mirrored lollipop plot and outcomes analysis now supports hazard ratios and landmark analysis. Arm-level copy number can now be compared across groups, as can any data in the generic assay format. We also enhanced the study view. Users can now add charts to summarize the copy number of a specific gene across the cohort. The option to add custom data charts now supports numerical data as well as categorical data. Filters in study view can now be manually submitted, which provides a performance improvement when applying multiple filters in a large cohort. Larger-scale performance improvements are currently underway. We continue to improve support for multimodal datasets incorporating derived data elements, including cell type counts and fractions per sample from imaging or single cell data. The MSK-SPECTRUM ovarian cancer study has samples profiled with bulk sequencing, scRNASeq, H&amp;E and mpIF imaging. Through integrations with CELLxGENE (single cell data) and Minerva (imaging), users can explore these data modalities in detail in isolation and query them jointly in cBioPortal. cBioPortal is open source (https://github.com/cBioPortal/). Development is a collaborative effort among groups at Memorial Sloan Kettering Cancer Center, Dana-Farber Cancer Institute, Childrens Hospital of Philadelphia, Princess Margaret Cancer Centre, Caris Life Sciences, Bilkent University and The Hyve. We welcome open source contributions from others in the cancer research community. Citation Format: Tali Mazor, Ino de Bruijn, Rima AlHamad, Calla Chennault, Corey Dubin, Jeremy Easton-Marks, Zhaoyuan Fu, Benjamin Gross, Charles Haynes, David M. Higgins, Jason Hwee, Prasanna K. Jagannathan, Mirella Kalafati, Karthik Kalletla, James Ko, Tim Kuijpers, Sowmiyaa Kumar, Priti Kumari, Ritika Kundra, Bryan Lai, Xiang Li, James Lindsay, Aaron Lisman, Qi-Xuan Lu, Ramyasree Madupuri, Angelica Ochoa, Yusuf Z. Özgül, Oleguer Plantalech, Matthijs N. Pon, Baby A. Satravada, Jessica Singh, Selcuk Onur Sumer, Pim van Nierop, Floris Vleugels, Avery Wang, Manda Wilson, Hongxin Zhang, Gaofei Zhao, Ugur Dogrusoz, Allison Heath, Adam Resnick, Trevor J. Pugh, Chris Sander, Ethan Cerami, Jianjiong Gao, Nikolaus Schultz. cBioPortal for Cancer Genomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1249.

Abstract 6476: Solving the real-world data challenge: A hybrid resourcing model to curate RWD at scale

Abstract Introduction: As cancer treatments become more complex, the need for structured real-world data (RWD) to support clinical research is critical. However, researchers often lack resources to curate data in-house. Organizations are challenged with timely data curation at the quality and scale needed for real world applications. Methods: As members of the AACR Project GENIE (Genomics Evidence Neoplasia Information Exchange) Biopharma Collaborative (BPC), Memorial Sloan Kettering Cancer Center (MSK) and Dana-Farber Cancer Institute (DFCI) partnered with Vasta Global, an Omega Healthcare company, to build a model for curating RWD at scale, allowing for cost-effective RWD curation while leveraging expert resources and best practices. The approach includes managing a hybrid onshore and offshore team with clear communication and recurring check-ins, cross-training curators on different EHRs to reallocate Vasta Global resources and maintain project pace, building program-specific clinical data curation training, establishing QA and delivery methods, standardizing data curation, assigning productivity standards, aligning data quality practices and benchmarks, and developing data visualizations and analytics to show progress and insights. Results: In Phase 1 of the AACR GENIE BPC, data was curated from four sites: MSK, DFCI, Vanderbilt Ingram Cancer Center (VICC) in Nashville, and Princess Margaret Cancer Centre, University Health Network (UHN) in Toronto. During Phase 1, MSK and DFCI, with Vasta Global’s assistance, delivered high-quality RWD for 6,475 patients (NSCLC = 1,591; CRC = 1,264; Bladder = 639; Breast = 957; Pancreas 989; and Prostate = 1,035). All data for these cohorts will be publicly available by Spring 2024 in the AACR Project GENIE cBioPortal. MSK and DFCI generated usable and fit-for-purpose RWD to help advance oncology clinical decision-making and data sharing. Conclusion: Accelerating RWD curation will empower the oncology community to leverage data-driven insights and advance treatment opportunities for cancer patients. Working alongside lead sites, a partner like Vasta Global enables researchers to leverage extensive expertise in the BPC data model, allowing for consistency and scalability of the BPC program. In this hybrid model, research partners can curate RWD in a cost-effective way, while remaining focused on core research responsibilities. Citation Format: Julia Rudolph, Kenneth L. Kehl, Melanie Bernstein. Solving the real-world data challenge: A hybrid resourcing model to curate RWD at scale [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6476.

Abstract 926: Adaptive universal platform for real-world observational studies (AUPROS): An emerging model for clinical, epidemiologic, and precision oncology research

Abstract Background: Adaptive Universal Platform for Real-world Observational Studies (AUPROS) is an emerging study design and platform for the generation of real-world evidence (RWE) particularly in malignancies with rare molecular aberrations. Here, we evaluate the efficiency of AUPROS as an innovative model for real-world observational studies in oncology. Methods: We conducted a mixed-methods study to evaluate three AUPROS studies at Princess Margaret Cancer Centre either locally or as a part of national and international collaborations: 1) METAL (Molecular Epidemiology of ThorAcic Lesions; n=11,378), 2) THANKS (Translational Head And NecK Study; n=3,506), and 3) CARMA (Canadian Cancers with Rare Molecular Alterations; NCT04151342; n=3,879). Specifically, we reviewed data collected, study elements, protocol language, coordination, institutional review boards (IRBs), and contracts. We also performed stakeholder-directed survey and discussions, analysis of funding, research output, and collaborations, as well as a Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis. Results: AUPROS is an innovative study design that borrows design elements from master protocol trials, adaptive trials, and master observational trials as well as retrospective and ambispective designs, enabling comprehensive data collection. The universality of AUPROS allowed for multi-purpose analyses of various real-world data (RWD) including epidemiological, clinical, patient-reported outcomes, biospecimens, and imaging data. The adaptive nature created opportunities for multi-source funding (e.g., academic, pharmaceutical, philanthropic, among others), as well as national/international collaborations and involvement in consortia (e.g., ILCCO, TCGA, BEACON, and INHANCE). Additionally, AUPROS has allowed the development of an expanding national RWE platform that involves collaborations among medical and radiation oncologists and surgeons across different tumor sites. As assessed by research output analyses, AUPROS provided a platform for enhanced research productivity in different areas and utilizing various data sources (METAL=130; THANKS=31; CARMA=5 publications). Our survey and SWOT analysis identified several cost and operational benefits of AUPROS over conventional observational studies, as well as several challenges pertinent to ethics approvals, sustainability, complex coordination, and data quality. Conclusions: AUPROS is an innovative model for real-world observational studies with significant logistical and methodological benefits over conventional RWD study designs. Our findings may help broaden the use of AUPROS to address emerging needs in the scope of precision oncology and clinico-epidemiological research. Citation Format: Samir H. Barghout, Stavroula Raptis, Luna Jia Zhan, Faisal Al-Agha, M Catherine Brown, Devalben Patel, Geoffrey Liu. Adaptive universal platform for real-world observational studies (AUPROS): An emerging model for clinical, epidemiologic, and precision oncology research [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 926.

The Survival Outcomes of the Metastatic Nonclear Cell Renal Cell Carcinoma in the Immunotherapy Era: Princess Margaret Cancer Centre Experience.

Immunotherapy (IO) with or without targeted therapy (TT) is the standard treatment for patients with metastatic clear cell renal cell carcinoma (RCC). The evidence supporting their use in metastatic nonclear cell renal cell carcinoma (nccRCC) subtypes is based on small prospective trials and retrospective analyses. Here, we report survival outcomes for patients with metastatic nccRCC treated with IO and/or TT at the Princess Margaret Cancer Centre, Toronto, ON, Canada. Demographics, disease characteristics, and survival outcomes were collected retrospectively. Overall (OS), progression-free survival (PFS), and objective response rates (ORR) were calculated. We identified 69 patients with metastatic nccRCC treated with IO and/or TT as the first-line treatment, and 36 (52.1%) patients as the second-line treatment. Median OS of the first line IO recipients (n = 12) and non-IO recipients (n = 57) was not reached (NR) and 17.2 months (95% confidence interval (95% CI): 7.3-27.0; P = 0.23), respectively. Median PFS of first-line IO recipients and non-IO recipients was NR and 4.7 months (95% CI: 3.7-5.6; P = 0.019), respectively. The ORR of IO recipients versus non-IO recipients was 50% versus 12.3% (P = 0.007). Median OS of the second-line IO recipients (n = 8) and non-IO recipients (n = 28) was NR and 6.3 months (95% CI: 3.2-9.3; P = 0.003), respectively. Median PFS of second-line IO recipients and non-IO recipients was 4.8 months (95% CI: 2.7-6.8) and 2.8 months (95% CI: 1.8-3.7; P = 0.014), respectively. ORR of IO recipients and non-IO recipients was 37.5% and 3.5%, respectively; P = 0.028. While the number of patients included in our retrospective review was small, our analysis suggested that patients with nccRCC have improved survival outcomes with IO treatment. Validation of prospective dataset is required before widespread clinical utilization.

Adapting an Adolescent and Young Adult Program Housed in a Quaternary Cancer Centre to a Regional Cancer Centre: Creating Equitable Access to Developmentally Tailored Support.

Adolescents and young adults (AYAs) with cancer, representing those between 15 and 39 years of age, face distinctive challenges balancing their life stage with the physical, emotional, and social impacts of a cancer diagnosis. These challenges include fertility concerns, disruptions to educational and occupational pursuits, issues related to body image and sexual health, and the need for age-appropriate psychosocial support within their communities. The Princess Margaret Cancer Centre (PM), a quaternary care center, established a specialized AYA program in 2014, offering holistic and developmentally tailored psychosocial support and currently, efforts are underway to expand this to other regions in the province to address the need for equitable access. The establishment process involves securing funding, conducting an environmental scan, identifying service gaps, developing clinical pathways, and implementing AYA supportive care. An accessible AYA program should also consider social determinants of health, social location, intersectionality, and an interdisciplinary health approach in understanding health inequities in AYA oncology care. This paper describes the processes implemented and challenges faced in creating a community-based AYA program beyond major resource-rich cities and efforts to address intersectionality.

The survival outcomes for men with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination deficiencies (HRD) treated with radium-223: Princess Margaret Cancer Centre (PMCC) experience.

179 Background: Radium-223 (223Ra) is a radiopharmaceutical that emits alpha particles and specifically targets bone metastases in mCRPC, where it has been shown to improve overall survival (OS). Since 223Ra induces double-strand DNA breaks, we hypothesized that patients with HRD may exhibit heightened sensitivity to 223Ra, resulting in improved survival outcomes compared to patients without HRD. Methods: This retrospective analysis was performed in men with mCRPC and bone metastases, with and without HRD, treated with 223Ra at PMCC. Demographics and disease characteristics were collected. Germline and/or somatic DNA sequencing data were identified. OS and progression free survival (PFS) were calculated using the Kaplan–Meier method; differences in outcomes were assessed using the log-rank test. Alkaline phosphatase (ALP) and prostate specific antigen (PSA) responses were calculated at 12 weeks post 223Ra treatment. Results: We identified 40 mCRPC patients who had germline and/or somatic DNA sequencing and received 223Ra between December 2015 and May 2022. The median age at the start of 223Ra was 76.5 (range: 66.5-80.8), and ECOG was 0/1 (75%). A total of 29 (72.5%) patients received 233 Ra following abiraterone or enzalutamide treatment while 10 (25%) received 233 Ra post docetaxel. Overall, 22 (54%) received ≥4 cycles of ²²³Ra. Median baseline PSA was 58.6 (range: 25.2-143) and median baseline ALP was 109 (range: 71.8-200). Germline/somatic HRD mutations were found in 9/40 (22.5%) patients (BRCA2 [n=6], CHEK2 [n=2], CDK12 [n=1]). Baseline characteristics were well balanced between HRD and non-HRD groups. With median follow up of 13.7 months, the median OS of HRD group vs. non-HRD group was 24 months (95%CI: 14-not evaluable [NE]) vs. 12 months (95%CI: 7-22); p=0.038). The median PFS of HRD group vs. non-HRD group was 5.7 months (95%CI: 3-NE) vs. 3.3 months (95%CI: 2.5-13.4); p=0.74). The median time to the next treatment of HRD group vs. non-HRD group was 4.2 months (95%CI: 3.1-NE) vs. 3.75 months (95%CI: 3.5-13.5); p=0.89. ALP response was 66.7% of HRD group vs. 58.1% of non-HRD group; p=0.72. PSA response was 33.3% of HRD group vs. 9.7% of non-HRD group; p=0.11. For all patients with ALP response, the three years survival probability of HRD group vs. non-HRD group was 33% vs. 11%; p=0.03. Conclusions: While the number of patients included in our review was small, our analysis suggested that patients with HRD may have a slight improvement in OS after 223Ra treatment. Validation in a prospective dataset is required, and whether HRD status has implications for other radiopharmaceuticals such as lutetium-177 remains to be seen.

Intraductal Prostate Cancer Affinity for Lymphatic-Predominant Metastases Through 18F-DCFPyL‒Prostate-Specific Membrane Antigen‒Positron Emission Tomography/CT Scans in Pretreatment Prostate Cancer Patients.

Intraductal prostate cancer (IDC) is linked to unfavorable oncologic outcomes, marked by distinctive cellular intrinsic pathway changes and intricate immunosuppressive microenvironments that could impact the way cancer spreads. The aim of this study was to determine whether the presence of IDC in prostate biopsy specimens obtained from patients before primary prostate cancer (PCa) treatment is associated with a lymph node metastatic propensity in prostate-specific membrane antigen (PSMA)‒positron emission tomography (PET)/CT. This was a cross-sectional analysis of all PCa patients undergoing a pretreatment 18F-DCFPyL-PSMA-PET/CT between January 1, 2016, and August 2021 at The Princess Margaret Cancer Centre. Outcomes were presence of any metastasis in the overall cohort, presence of lymphatic vs no metastases, and presence of lymphatic vs bone metastasis among patients who underwent PSMA-PET/CT as PCa primary staging. The associations between IDC presence on the prostate biopsy and the study outcomes were evaluated using univariable and multivariable logistic regression analyses. The cohort consisted of 120 patients. IDC and cribriform pattern were observed in 55 (46%) and 48 (40%) prostate biopsies, respectively. Overall, 52 patients (43%) had evidence of metastasis. Presence of IDC on biopsy was associated with increased odds of overall metastasis (odds ratio: 2.47, 95% CI: 1.09-5.61, P = .03). Of the 52 patients with evidence of metastasis, 41 (79%) had evidence of lymphatic metastasis. Presence of IDC on biopsy was associated with significantly increased odds of lymphatic metastasis vs nonmetastases (odds ratio: 3.03, 95% CI: 1.24-7.40, P = .01). The identification of IDC morphology in prostate biopsy specimens has been observed to be significantly linked with lymph node metastasis on 18F-DCFPyL-PET/CT imaging in a PCa pretreatment staging setting. We found that presence of IDC in prostate biopsy appears to be a marker for lymph node metastasis on 18F-DCFPyL-PET/CT.

Virtual Cancer Care Beyond the COVID-19 Pandemic: Patient and Staff Perspectives and Recommendations.

COVID-19 catalyzed rapid implementation of virtual cancer care (VC); however, work is needed to inform long-term adoption. We evaluated patient and staff experiences with VC at a large urban, tertiary cancer center to inform recommendations for postpandemic sustainment. All physicians who had provided VC during the pandemic and all patients who had a valid e-mail address on file and at least one visit to the Princess Margaret Cancer Centre in Toronto, Canada, in the preceding year were invited to complete a survey. Interviews and focus groups with patients and staff across the cancer center were analyzed using qualitative descriptive analysis and triangulated with survey findings. Response rates for patients and physicians were 15% (2,343 of 15,169) and 41% (100 of 246), respectively. A greater proportion of patients than physicians were satisfied with VC (80.1 v 53.4%; P < .01). In addition, fewer patients than physicians felt that virtual visits were worse than those conducted in person (28.0 v 43.4%; P < .01) and that telephone and video visits negatively affected the human interaction that they valued (59.8% v 82.0%; P < .01). Major barriers to VC for patients were respect for care preferences and personal boundaries, accessibility, and equitable access. For staff, major barriers included a lack of role clarity, dedicated resources (space and technology), integration of nursing and allied health, support (administrative, clinical, and technical), and guidance on appropriateness of use. Patient and staff perceptions and barriers to virtual care are different. Moving forward, we need to pay attention to both staff and patient experiences with virtual care since this will have major implications for long-term adoption into clinical practice.

Quality of surveillance in patients with completely resected gastroenteropancreatic neuroendocrine tumors.

591 Background: The incidence and prevalence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are increasing worldwide. Surgery remains the only curative modality. Because of limited data on patterns of recurrence, real-world surveillance practices and duration vary widely. In 2018, the Commonwealth Neuroendocrine Tumour Research Collaboration (CommNETs) published consensus surveillance guidelines for patients with completely resected GEP-NETs. Our aim was to assess adherence to the CommNETs guidelines for surveillance practices for this patient population at our center. Methods: We conducted a retrospective cohort study of patients with GEP-NETs seen for a new patient appointment at Princess Margaret Cancer Centre (PMCC) from 2019-2022. Patients were included if they had a completely resected GEP-NET and followed on surveillance at our center. Demographic and tumor characteristics, surveillance practices, and clinical outcomes were abstracted. Summary statistics and a descriptive comparison of surveillance practices were completed. Results: Out of the 374 new patient appointments, 87 met the inclusion criteria. The main reasons for exclusion were metastatic disease at presentation (n=128), primary tumor not resected (n=58), and patients not followed at PMCC (n=49) so their surveillance practices cannot be determined from our records. The primary tumor sites were pancreatic (n=50, 57%), appendiceal (n=15, 17%), small bowel (n=11, 13%), rectal (n=10, 12%), and colon (n=1, 1%). Thirty-eight patients (44%) had stage 1 disease, 21 patients (24%) had stage 2, and 28 patients (32%) had stage 3. Forty-six patients (53%) had a WHO tumor grade of 1, 36 patients (41%) had grade 2, and 5 patients (6%) had grade 3. The median duration of follow-up was 18.2 months. Adherence to ordering the recommended surveillance investigations was 23% (20/87). Within the adherent cases, there was a higher number of appendiceal, WHO grade 1, and stage 1 tumors. Sixty-six patients (76%) had at least one test that was not recommended by the guidelines. The most frequent unnecessary tests were CT chest in all patient groups and CT pelvis in pancreatic NETs (Table). Six patients were lost to follow up and none discharged from surveillance. Conclusions: Adherence to the CommNETs consensus guidelines was low at our center, suggesting the guidelines had a minor impact on surveillance practices and providing an area for improvement in process of care and resource utilization. [Table: see text]

De novo metastatic versus recurrent gastroesophageal cancer: A single-centre retrospective analysis.

282 Background: Outcomes remain poor for patients with metastatic gastric, gastroesophageal and esophageal adenocarcinoma (GEAC) with median survival of 14 months with combination chemotherapy and immunotherapy as per the Checkmate 649 trial. There is limited data to clarify if any differences exist between denovo metastatic and recurrent GEAC in terms of survival and response to systemic therapy. We compare the baseline characteristics and outcomes for patients with denovo metastatic and recurrent GEAC in our cohort. Methods: A retrospective observational analysis was conducted to include patients with metastatic GEAC reviewed at Princess Margaret Cancer Centre between 2007 and 2021. Baseline characteristics including age, sex, race, performance status and Charlson Comorbidity index (CCI) were reviewed. Outcomes of interest included overall survival (OS), progression free survival on first line (PFS1) and second line (PFS2) systemic therapy and disease-free interval (DFI) in the recurrent group (defined as time between initial diagnosis and development of recurrent disease). OS was calculated from diagnosis of stage IV disease. Cox proportional hazards and Kaplan Meier curves were used to compare OS, PFS1 and PFS2. Outcomes were adjusted for baseline characteristics. The effect of DFI on outcomes was evaluated in the recurrent group. Results: Our cohort consisted of 619 cases, of which 456 (73.6%) were denovo metastatic and 163(26.4%) were recurrent. The majority (71%) were male, non-Asian (85%) and median age for the cohort was 60 years. There were no significant differences in baseline characteristics and biomarker status (HER2, MSI) between denovo and recurrent groups. Number of metastatic sites was significantly higher in denovo group (Mean:2.3 vs 1.8, p&lt;0.001). A significantly higher percentage of patients received immunotherapy in the first line setting in the recurrent group (8% vs 4%, p:0.04). Using multivariate cox regression and after adjusting for age, performance status and CCI, there was a significant difference in OS favoring recurrent group (aHR:0.70, 95% CI 0.57-0.86, p=&lt;0.001). Using Kaplan Meier curves, median OS was 18.08 months in the recurrent group vs 14.62 months in the denovo metastatic group. There was a significant difference in PFS1 using a multivariate model in favor of the recurrent group (aHR 0.81,95% CI 0.67-0.99, p=0.04), as well as similar improvement in PFS2 for the recurrent group (aHR:0.69,95% CI 0.52-0.92, p=0.01). In the recurrent group, OS did not differ significantly between DFI &lt;6 months, 6-12 months or &gt;12 months. Conclusions: Our results show a significantly better OS, PFS1 and PFS 2 for recurrent as compared to denovo metastatic GEAC for patients treated in the 1st line metastatic setting in a large single-centre retrospective analysis. More in depth analysis of molecular differences in patient tumors is underway and may help to explain better outcomes.

How representative are participants in geriatric oncology clinical trials? The case of the 5C RCT in geriatric oncology: A cross-sectional comparison to a geriatric oncology clinic

IntroductionFrail older adults make up a substantial portion of the older adult population. However, frail patients are often excluded from randomized controlled trials. This underrepresentation restricts the extent to which trial findings can be generalized to this population. We compared a sample from the Canadian 5C Randomized Controlled Trial investigating comprehensive geriatric assessment (CGA) in the geriatric oncology setting in terms of frailty to patients referred to the Older Adults with Cancer Clinic (OACC) to determine if the trial sample was representative of the normal geriatric oncology practice. Materials and MethodsBaseline CGA data of 5C Trial participants seen at the Princess Margaret Cancer Centre (PM), were compared to data from OACC patients that were seen during the duration of the 5C trial (between April 2018 and April 2020) and that satisfied the 5C inclusion criteria. To assess the frailty of samples, sex, age, disease site, comorbidity level, medical optimization, social supports, functional status, falls risk, nutrition, cognition, and mood were compared between 5C participants and OACC patients using Fisher's exact and independent samples t-test. ResultsA sample of 115 5C participants and 205 OACC patients were included. The mean age of 5C participants and OACC patients was 75.4 and 81.6 years, respectively (p < 0.001). The distribution of disease sites was significantly different between the samples (p < 0.001) and OACC patients were also significantly more impaired compared to 5C participants in comorbidity (23.4% versus 10.4% high comorbidity) (p = 0.001), IADL dependence (55.1% versus 42.6%) (p = 0.036), impaired physical function (70.6% versus 31.3%) (p < 0.001), falls risk (67.8% versus 27%) (p < 0.001), impaired nutrition (55.6% versus 40.9%) (p = 0.014), and cognition (47.2% versus 10%) (p < 0.001). There were no differences in sex, medication optimization, poor social supports, and impaired mood between the samples. DiscussionThe 5C sample was less frail and younger than patients seen in the geriatric oncology clinic. Finding strategies to address barriers to the inclusion of frailer older adults is important to increase their representation in future trials to allow findings to be generalized to this vulnerable population.Trial Registration: Clinicaltrials.gov # NCT03154671

Outcomes of intensive and nonintensive blast-reduction strategies in accelerated and blast-phase MPN

AbstractTransformation of BCR::ABL1-negative myeloproliferative neoplasms (MPN) to an accelerated or blast phase is associated with poor outcomes. The efficacy of acute myeloid leukemia (AML)–type intensive and nonintensive hypomethylating agent–based regimens is not well studied. We therefore performed a retrospective analysis of patients with MPN-AP/BP (N = 138) treated with intensive (N = 81) and nonintensive (N = 57) blast-reduction strategies. We used clinically relatable response criteria developed at the Princess Margaret Cancer Centre. The overall best response, comprising complete remission (CR), complete remission with incomplete hematologic recovery (CRi), and reversion to chronic phase MPN (cMPN), in the intensive and nonintensive groups was 77% (62 of 81) and 39% (21 of 54), respectively. Similar overall best response rates were observed in patients receiving induction with daunorubicin combined with cytarabine arabinoside (daunorubicin + ara-C) (74% [23 of 31]) or FLAG-IDA/NOVE-HiDAC (78% [39 of 50], P = .78). However, patients receiving daunorubicin + ara-C more often required second inductions (29% [9 of 31] vs 4% [2 of 50], P = .002). Most responses in the entire cohort were reversions to cMPN (55 of 83 [66%]). CR and CRi comprised 30% (25 of 83) and 4% (3 of 83) of responses, respectively. Mutations in TP53 (overall response [OR] 8.2 [95% confidence interval [CI] 2.01, 37.1], P = .004) and RAS pathway (OR 5.1 [95%CI 1.2, 23.7], P = .03) were associated with inferior treatment response for intensively treated patients, and poorer performance status (Eastern Cooperative Oncology Group) was associated with inferior treatment response in both intensively (OR 10.4 [95% CI 2.0, 78.5], P = .009) and nonintensively treated groups (OR 12 [95% CI 2.04, 230.3], P = .02). In patients with paired samples before and after therapy (N = 26), there was a significant residual mutation burden remaining irrespective of response to blast-reduction therapy.

Defining an Abnormal Geriatric Assessment: Which Deficits Matter Most?

At present, there is no clear definition of what constitutes an abnormal geriatric assessment (GA) in geriatric oncology. Various threshold numbers of abnormal GA domains are often used, but how well these are associated with treatment plan modification (TPM) and whether specific GA domains are more important in this context remains uncertain. A retrospective review of the geriatric oncology clinic database at Princess Margaret Cancer Centre in Toronto, Canada, including new patients seen for treatment decision making from May 2015 to June 2022, was conducted. Logistic regression modelling was performed to determine the association between various predictor variables (including the GA domains and numerical thresholds) and TPM. The study cohort (n = 736) had a mean age of 80.7 years, 46.1% was female, and 78.3% had a VES-13 score indicating vulnerability (≥3). In the univariable analysis, the best-performing threshold number of abnormal domains based on area under the curve (AUC) was 4 (AUC 0.628). The best-performing multivariable model (AUC 0.704) included cognition, comorbidities, and falls risk. In comparison, the multivariable model with the sole addition of the threshold of 4 had an AUC of 0.689. Overall, an abnormal GA may be best defined as one with abnormalities in the domains of cognition, comorbidities, and falls risk. The optimal numerical threshold to predict TPM is 4.

First impressions: A prospective evaluation of patient-physician concordance and satisfaction following the initial medical oncology consultation.

An especially significant event in the patient-oncologist relationship is the initial consultation, where many complex topics-diagnosis, treatment intent, and often, prognosis-are discussed in a relatively short period of time. This study aimed to measure patients' understanding of the information discussed during their first medical oncology visit and their satisfaction with the communication from medical oncologists. Between January and August 2021, patients without prior systemic treatment of their gastrointestinal malignancy (GI) attending the Princess Margaret Cancer Centre (PMCC) were approached within 24 h of their initial consultation to complete a paper-based questionnaire assessing understanding of their disease (diagnosis, treatment plan/intent, and prognosis) and satisfaction with the consultation. Medical oncology physicians simultaneously completed a similar questionnaire about the information discussed at the initial visit. Matched patient-physician responses were compared to assess the degree of concordance. A total of 184 matched patient-physician surveys were completed. The concordance rates for understanding of diagnosis, treatment plan, treatment intent, and prognosis were 92.9%, 59.2%, 66.8%, and 59.8%, respectively. After adjusting for patient and physician variables, patients who reported treatment intent to be unclear at the time of the consultation were independently associated with lower satisfaction scores (global p = 0.014). There was no statistically significant association between patient satisfaction and whether prognosis was disclosed (p = 0.08). An in-depth conversation as to what treatment intent and prognosis means is reasonable during the initial medical oncology consultation to ensure patients and caregivers have a better understanding about their cancer.

Considering Older Patients As Candidates for Auto Stem Cell Transplants: A Comprehensive Study on Toxicities and Survival Analysis

Introduction: High-dose chemotherapy and autologous stem cell transplantation (ASCT) are commonly used for relapsed/refractory (R/R) Hodgkin (HL) and non-Hodgkin lymphoma (NHL). However, concerns about treatment-related mortality (TRM) and toxicity limit its use in older patients (pts). Existing evidence suggests higher rates of complications and inferior overall survival (OS) in older pts, but conflicting findings suggest that outcomes may be influenced by comorbidities rather than age ( Lahoud O, Curr Oncol Rep. 2015). Our study comparing ASCT outcomes and toxicities in lymphoma pts in younger and older age groups. Methods: In this retrospective study, we analyzed lymphoma pts who underwent ASCT at the Princess Margaret Cancer Centre from January 2015 to December 2019. After Institutional Review Board approval, clinical data was collected from institutional databases and patient charts. The hematopoietic cell transplantation comorbidity index (HCT-CI) and Charlson Comorbidity Index (CCI) were retrospectively calculated. Response assessment was done by Lugano 2014 classification. Grade 3-5 nonhematologic toxicities were collected from admission to day 100 using Common Terminology Criteria for Adverse Events version 5. Overall survival (OS) and progression-free survival (PFS) were calculated from date of transplant to death or disease progression. OS and PFS assessed via Kaplan-Meier; log rank tests and Cox regression performed. The patients were divided into two age groups: Group A (&amp;lt;65 years) and Group B (≥65 years). Results: There were 334 pts who underwent ASCT. 332 pts were analyzed; 2 pts were lost to follow-up and 16 pts were day 1 transfers, making acute toxicity data unavailable. The median age was 53 (range: 18-71), 17% of pts being aged ≥65. The majority of pts (69%) had NHL (table 1). The Eastern Cooperative Oncology Group (ECOG) performance status was ≤1 for 91%. Group B had a higher proportion of pts with ECOG score =2 (18% vs 7%, p &amp;lt; 0.001 ) and higher CCI (88% vs 27% , p &amp;lt; 0.001). NHL and mantle cell lymphoma (MCL) were more prevalent in Group B (93%, 23% vs 68%, 12% respectively, p&amp;lt; 0.001). Thirteen percent of NHL pts were transformed disease. Both groups had similar percentage of pts with central nervous system (CNS) lymphoma (~ 5%). Conditioning regimens varied based on lymphoma type: most of the HL/aggressive lymphomas: Etoposide+Melphalan (ML), CNS lymphoma: Thiotepa based regimen, and MCL Cytarabine + ML+/- Total Body Irradiation. The majority (83%) were treated for R/R disease, while 17% received it as first-line treatment. Prior to transplant, 76% of pts were in CR. Median follow-up was 38 months. Median OS was not reached for Group A, and 73 months for Group B. Five year OS were 82% and 74% respectively (p = 0.05). Median PFS was 75.2 months for Group A and 43.0 months for Group B, with 5-year PFS of 54% and 47% respectively (p = 0.2). Twenty percent of pts died during follow-up, with only 4% being NRM. From the entire cohort 3% of patients died within 100 days post-transplant, with no difference between groups. Three pts died within 100 days of ASCT with 2 deaths from sepsis (Group A) and 1 death from Respiratory failure (Group B). Common transplant-related toxicities did not differ significantly between groups (figure 1). Group B had significantly higher rates of Renal (7%vs 18%), Respiratory (16% vs 6%), and Metabolism abnormalities (14% vs 5%) (p = 0.021-0.028). Group B needed more blood product transfusions by 100 days post-transplant: Packed Cells (mean) 1.7 vs 1.1 units (p 0.08), Platelets (mean) 3 vs 1.9 units (p 0.002). Group B had a longer average length of stay 18 days vs. 14 days (p &amp;lt; 0.001). About 6% of pts required ICU admission, and 4% were discharged to rehabilitation/long-term care facilities, with no group differences. Conclusions: The study concludes that ASCT can be safely performed in appropriately selected elderly pts. TRM rates were not significantly higher in older compared to younger pts with lymphoma. However, older pts did experience higher rates of specific toxicities including renal failure, pulmonary complications, metabolism abnormalities, longer hospital stays, and increased transfusion requirements. In the multivariate analysis, older pts exhibited shorter OS, influenced by lymphoma type and treatment response. Further research is needed to develop risk stratification and geriatric assessments to improve toxicity prediction in elderly pts undergoing ASCT.

Management and Outcomes for Primary Mediastinal B-Cell Lymphoma Patients with Partial Metabolic Response

Background: The optimal management of patients with primary mediastinal B-cell lymphoma (PMBCL) who experience a partial metabolic response (PMR) on FDG-PET after initial systemic therapy is unclear. This study aimed to investigate different management strategies and outcomes for PMBCL patients who achieved PMR following primary systemic therapy, utilizing a single-center retrospective design. Methods: We reviewed the electronic medical records of 121 PMBCL patients who underwent post-chemotherapy PET scans at the Princess Margaret Cancer Center, Toronto, from January 2009 to September 2021. Using Modified Lugano criteria (2014), post-chemotherapy PET scan results were evaluated, with Deauville score (DS) 0-3 considered a complete metabolic response. Demographic, clinical, and imaging characteristics of the PMBCL population were analyzed. The Kaplan-Meier method was used to estimate progression-free survival (PFS), measured from the time of the post-systemic therapy PET. Results: A total of 121 patients with PMBCL underwent post-chemotherapy PET scans. Among them, 49 patients (40%) demonstrated incomplete metabolic response (DS4-5) Among these 49 patients, 12 showed primary refractory disease, while 37 demonstrated a partial metabolic response (PMR, DS4). The median age at diagnosis of the 37 patients with PMR was 30.8 years (range:18.4 - 52.8 years), and 20 (54%) were female. The median length of follow-up for these patients was 3.7 years (range: 0.4 to 9.2 years). Most PMR patients were stage I/II (26 patients, 70.3%), while the remaining were stage III (2 patients, 5.4%), or stage IV (8 patients, 21.6%), and 26 (70.3%) had a large mediastinal mass (maximum diameter exceeding 10cm). Initial systemic treatment was R-CHOP-21 (34 patients, 91.9%), R-CHOP combined with dose-adjusted R-EPOCH (2 patients, 5.4%), and dose-adjusted EPOCH (1 patient, 2.7%). Thirty one patients (83.8%) received 6 cycles. Following treatment strategies were employed to manage PMR: 1) radiation therapy (RT) only with or without biopsy in 30 patients (80.1%); 2) an observational approach (repeating PET scans without immediate treatment) in 3 patients (8.1%); 3) salvage chemotherapy in 3 patients (8.1%) and other approach in 1(2.7%) patient. The 2-year progression-free survival (PFS) rate for all patients with incomplete metabolic response (n=49) was 74.5% (95% CI = 62.5% to 88.9%). For patients with primary progression on post-chemotherapy PET scans the 2-year PFS (ie free of 2nd progression) was 40% (18.7% to 85.5%), while the 2-year PFS for patients with PMR was 85.4% (74.3% to 98.1%). PMR patients who underwent radiotherapy (RT) had the 2-year PFS rate of 92.7% (95% CI: 83.5% to 100.0%). No progression or relapsed occurred among the 3 patients with PMR who were managed with repeating PET scans without immediate further treatment. Conclusion: This study replicates prior work demonstrating a higher rate of incomplete metabolic response for PMBCL patients following R-CHOP-21 than typically reported for DLBCL. RT to persistent PET-avid sites is associated with excellent PFS. The favorable outcome of PMR patients without any additional treatment illustrates the non-trivial risk of false-positive PET scans following systemic therapy, and the need to identify criteria that can distinguish those who need additional treatment from those who can be safely observed.