Provincial Cancer Registry Research Articles

Effect of Treatment Delivery Schedule for Patients With Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Ablative Radiation Therapy: A Population-Based Analysis

PurposeThe optimal stereotactic ablative body radiotherapy (SABR) delivery schedule in stage I non-small cell lung cancer (NSCLC) remains unclear. This population-based study investigated grade ≥ 2 toxicity rates, local failure (LF), and overall survival (OS) in patients treated with 48 Gy in 4 fractions scheduled every other day (QOD) versus daily with weekends (QDW) and consecutive daily without weekends (QD). Materials and MethodsBetween January 2019 and June 2022, treatment records using 48 Gy in 4 fractions were extracted from a provincial cancer registry and grouped by delivery as QOD, QDW, or QD. Toxicity events were recorded using CTCAE v5.0. The Kaplan-Meier method was used to compute OS while LF was calculated using cumulative incidence methods with death as a competing risk. Cox regression analyses and Fine-Gray modelling was used to assess for variables associated with OS and LF, respectively. ResultsOf 404 patients meeting study criteria, 190, 111, and 103 received QOD, QDW, and QD SABR, respectively. More patients receiving QDW SABR were medically inoperable and more patients receiving QD SABR had tumors abutting the chest wall. Median follow-up was 29.5 months (interquartile range [IQR] 19.2-38.4). Overall toxicity was low, with crude rates of acute and late grade ≥ 2 toxicity not being statistically different among the groups. No grade 4 or 5 toxicities were recorded. LF rates at 24 months were not different at 7.5% (95% confidence interval [CI] 3.7-11.3), 9.5% (95% CI 3.9-15.1), and 11.0% (95% CI 4.9-17.2) for the QOD, QDW, and QD groups, respectively (p = 0.60). QDW and QD schedules were not associated with LR. Similarly, no significant differences in median OS were found among the QOD, QDW, and QD groups at 47.5 months (95% CI 39.26-55,74), 52.7 (95% CI 34.7-70.7), and 49.0 months (95% CI 31.6-66.4), respectively. QDW and QD schedules were not associated with OS. ConclusionsThis population-based study demonstrated no statistically significant differences in grade ≥ 2 toxicity rates, LF, and OS for stage I NSCLC patients treated with lung SABR using 48 Gy in 4 fractions delivered QOD, QDW, and QD. Patient convenience and optimization of resources may be considered when choosing a lung SABR treatment delivery schedule.

Testicular germ cell tumor survival among children, adolescents, and young adults: A population-based retrospective cohort study.

10035 Background: While testicular germ cell tumor (TGCT) overall survival (OS) exceeds 90%, some patient groups, such as adolescents, have inferior event free survival (EFS) outcomes. There is a paucity of granular, population-derived data about outcomes in children, adolescents, and young adults (CAYA) with TGCT, limiting a deeper understanding of the factors that impact their survival. Methods: All male CAYA (ages 11-21 years) in Ontario, Canada diagnosed with TGCT between 1992-2021 were identified using provincial cancer registries. Detailed disease and treatment characteristics were chart abstracted for ~2/3 of the cohort and determined through health administrative databases for the remainder. We assessed 5-year OS and EFS (first of death, recurrence/progression, or subsequent malignant neoplasm [SMN]) using Kaplan-Meier analysis and the log rank test. Follow-up started at TGCT diagnosis, except for survival after SMN or recurrence, where follow-up started at event date. Results: 748 TGCT patients were identified; 521 were chart abstracted and thus had EFS data available. Median age at diagnosis was 19 years (interquartile range:18-21) and 83.6% had non-seminoma histology. OS and EFS ± standard error (SE) were (94.7 ± 0.8 %, n=748) and (76.4 ± 1.9%, n=521), respectively. Among patients with chart abstracted data, OS and EFS differed by cancer extent at diagnosis and were lowest among CAYA with non-lung organ metastases (Table). Patients who underwent retroperitoneal lymph node dissection (RPLND) for initial treatment (91/521) had higher survival than those who did not (OS 96.6 ± 1.9% vs 93.7 ± 1.2%, p=0.04; EFS 87.6 ± 3.5 % vs 74.1 ± 2.1 %, p=0.0008), particularly CAYA with lung-only organ metastases. OS post SMN (n=28) was 77.3 ± 8.2%, with lower OS after non-TGCT SMN (50.8 ± 14.4%, n=13) than second primary TGCT (100 ± 0%, n=15), p=0.002. OS after recurrence/progression (n=116) was superior in the 59 who did not receive chemotherapy at initial diagnosis (89.7 ± 4%) compared to the 57 who had initial chemotherapy (65.9 ± 6.4%; p=0.0001). Conclusions: CAYA with TGCT have low EFS, consistent with previous studies. The extent of metastasis is a significant predictor. Efforts are needed to improve the survival outcomes of young TGCT patients with organ metastasis at diagnosis, and those who recur or develop a non-TGCT SMN. [Table: see text]

Impact of Pre-Diagnostic Risk Factors on Short- and Long-Term Ovarian Cancer Survival Trajectories: A Longitudinal Observational Study.

Tumor- and treatment-related factors are established predictors of ovarian cancer survival. New studies suggest a differential impact of exposures on ovarian cancer survival trajectories (i.e., rapidly fatal to long-term disease). This study examined the impact of pre-diagnostic risk factors on short- and long-term ovarian cancer survival trajectories in the Canadian context. This population-based longitudinal observational study included women diagnosed with invasive epithelial ovarian cancer from 1995 to 2004 in Ontario. Data were obtained from medical records, interviews, and the provincial cancer registry. Extended Cox proportional hazard models estimated the association between risk factors and all-cause and ovarian cancer-specific mortality by survival time intervals (<3 years (i.e., short-term survival), 3 to <6 years, 6 to <10 years, and ≥10 years (i.e., long-term survival)). Among 1421 women, histology, stage, and residual disease were the most important predictors of all-cause mortality in all survival trajectories, particularly for short-term survival. Reproductive and lifestyle factors did not strongly impact short-term overall survival but were associated with long-term overall survival. As such, among long-term survivors, history of breastfeeding significantly decreased the risk of all-cause mortality (HR 0.65; 95% CI 0.46, 0.93; p < 0.05), whereas smoking history (HR 1.75; 95% CI 1.27, 2.40; p < 0.05) and obesity (HR 1.81; 95% CI 1.24, 2.65; p < 0.05) significantly increased the risk of all-cause mortality. The findings were consistent with ovarian cancer-specific mortality. These findings suggest that pre-diagnostic exposures differentially influence survival time following a diagnosis of ovarian cancer.

The role of surgeon specialty in management and survival of malignant ovarian germ cell tumors: A population-based study

ObjectivesThe aim of this study is to describe management and survival in adult patients with malignant ovarian germ cell tumors (MOGCT) undergoing surgery by general gynecologists (GG) versus gynecologic oncologists (GO). MethodsThis is a population-based retrospective cohort study, including patients (age ≥ 18 years old) with MOGCT identified in the provincial cancer registry of Ontario, (1996–2020). Baseline characteristics, surgical and chemotherapy treatment were compared between those with surgery by GG or GO. Cox proportional hazards (CPH) model was used to determine if surgeon specialty was associated with overall survival (OS). ResultsOverall, 363 patients were included. One-hundred and sixty (44%) underwent surgery by GO and 203 (56%) by GG. There were higher rates of stage II-IV in the GO group (27.5% vs 3.9%, p < 0.001, and higher proportion of chemotherapy (64.4% vs 37.4%, p < 0.0001).Five-year OS was 90% and 93% in the GO vs GG groups, respectively (p = 0.39). CPH model showed factors associated with increased risk of death were older age at diagnosis (HR 1.09, 95% CI 1.07–1.12) and chemotherapy (HR 3.12, 95% CI 1.44–6.75). Surgeon specialty was not independently associated with all-cause death (HR 1.04, 95% 0.51–2.15, p = 0.91). ConclusionsIn this group of MOGCT, 5-year OS was not significantly different between patients having surgery by GO compared to GG. Nevertheless, survival rates were lower than expected in the GG group despite their low-risk features. Further exploration is warranted regarding the reasons for this and whether patients with suspected MOGCT may benefit from early assessment by GO for optimal management.

Hypofractionated Radiotherapy for Hematological Malignancies during COVID-19 Pandemic and Beyond.

Conventionally fractionated radiotherapy (RT) has shown to have excellent local control in hematological malignancies (HM). Up to date there is none or scant literature about the use of hypofractionated radiotherapy (HFRT) for the treatment of HM, this single institution study analyzed the efficacy of HFRT in HM. We hypothesized that HFRT in HM will result in a similar local tumor control that has been reported with standard fractionated RT. In this retrospective study, we analyzed the data from patients within the provincial cancer registry diagnosed with HM treated with a curative intent using HFRT regimens suggested by International Lymphoma Radiation Oncology Group between 2020-2022 during the COVID-19 pandemic. Primary outcome of the study was overall response rate (ORR), measured as complete response (CR), partial response (PR) or stable disease (SD) within the irradiated field determined radiologically or clinically post completion of RT. Secondary end point was freedom from local progression (FFLP), calculated from the date of initiation of RT to the first date among in-field progression, death, and last follow-up. Summary statistics were used to describe cohort and treatment characteristics. FFLP was calculated by 1 minus cumulative incidence accounting for competing risk (i.e., death). Of the 36 patients included for analysis, 18 were aggressive non-Hodgkin lymphoma (NHL), 9 were indolent NHL, 6 were Hodgkin lymphoma (HL) and 3 were other HM. Among them 25 had consolidation RT and 11 had definitive RT. HFRT daily dose per fraction ranged from 2.67 Gy to 5 Gy and total dose regimens ranged from 18 Gy to 42.5 Gy in 6 - 17 fractions and median equivalent dose in 2 Gy fractions (EQD2) for alpha/beta = 10Gy was 36 Gy (±7.5). ORR for the entire cohort was 94.4%. With a median follow up of 13.2 months, FFLP at one year for the entire cohort was 91.5% and death without infield progression was 8.7%. Among the 4 patients who had in radiation field recurrence, 2 had aggressive NHL and 2 had HL. No grade 3 or 4 acute toxicities were reported. This retrospective study using HFRT showed an ORR and FFLP comparable to historical studies using standard fractionation. Further long-term follow-up is warranted to confirm these findings.

The impact of national holidays on postoperative radiotherapy of squamous cell carcinoma of the head and neck.

Delays in starting postoperative radiotherapy (PORT) have been established as negative predictors for clinical outcomes in head and neck squamous cell carcinomas (HNSCC). Our study aimed to examine the effect of delays during PORT, and the impact of national holidays in Canada, a publicly funded system, on oncologic outcomes such as Overall Survival (OS) and Local Recurrence (LR). The provincial cancer registry was queried to obtain demographic, pathologic, and outcomes data from cancer patients treated for all squamous cell carcinomas of the head and neck region treated between January 1, 2007 and November 30, 2019. All extracted information was cross-referenced and supplemented by chart review of patient electronic medical records. Extracted data were analyzed for OS and LR, in the context of Canadian national holidays causing delays during PORT. 1433 patients treated for HNSCCs were identified, of whom 338 were treated curatively with surgery followed by PORT. 68.6% of patients experienced at least one day of interruption during treatments due to holidays. LR was 15.4% and OS was 59.6% at 5years. Treatment interruptions by holidays were predictive of local recurrence (HR, 2.38; 95% CI 1.17-4.83; p=0.017). Patients that developed early recurrence prior to PORT had very poor oncologic outcomes. Our findings were consistent with previously published studies in limiting the interval between surgery and PORT. We identified the novel finding of paired holidays as a significant predictor in determining LR, suggesting the importance of modifying RT delivery schedules and timing.

Prognostic role of HER2 expression in patients with ER-positive/HER2-negative breast cancer: Results from a population-based cancer registry study.

547 Background: Estrogen Receptor (ER)-positive (+)/Human Epidermal Growth Factor Receptor 2 (HER2)-negative (-) breast cancers (BCs) express variable protein levels of both ER and HER2, which can influence prognosis. Methods: We evaluated all invasive ER+/HER2- BCs (n = 3633) that were diagnosed and systematically collected by the Parma Province Cancer Registry, Italy, from 2004 to 2018. Tumors were classified by HER2 (IHC score of 0, 1+ or 2+ with negative FISH) and ER status (ER-low [1-9%], ER-moderate [10-79%] or ER-high [80-100%]). Comparisons of clinicopathologic characteristics and disease outcome were performed. Results: BCs with late-stage diagnosis ( P = 0.04), high histologic grade ( P &lt; 0.0001), or high proliferative rate ( P &lt; 0.0001) were more likely HER2 2+/FISH-. The rate of ER-high BCs did not change from 2675 of 2938 (91%) HER2 0 tumors to 508 of 560 (90.7%) HER2 1+, and 124 of 135 (91.9%) HER2 2+/FISH- tumors. Correspondingly, ER-low BCs were not enriched among HER2 0 tumors compared to the other tumors with different HER2 expression ( P = 0.6). The 5-year overall survival (OS) for HER2 2+/FISH- BCs was lower than that for HER2 0 or 1+ tumors ( P = 0.03). ER-low/moderate tumors were associated with poorer OS in comparison with ER-high BCs ( P &lt; 0.0001). HER2 2+/FISH- status was detrimental to OS among patients (pts) with ER-high tumors ( P = 0.04), while this finding was not observed among ER-low/moderate BCs ( P = 0.21). An interaction between HER2 2+/FISH- expression and ER-high status was found for poorer OS after adjusting for prognostic variables (HR = 1.7; 95% CI: 1.1-2.9). Conclusions: The prognostic role of HER2 expression in pts with ER-positive/HER2-negative BCs seems to be restricted to ER-high tumors, while the worse prognosis of tumors with lower ER expression is not associated with HER2 status. These findings may help identify optimal patient inclusion criteria for clinical trials with novel anti-HER2 therapies in ER-positive/HER2-negative disease.

Regional disparities in cancer survival in Iran: Insight from a National Surveillance of Cancer Survival in Iran (IRANCANSURV)

Background and objectivesWe aimed to investigate geographical disparity in cancer survival in 9 provincial population-based cancer registries in Iran from 2015 to 2016. Material and methodIn the current study, data from 90,862 adult patients (aged >15 years) diagnosed with cancer were retrieved from 9 population-based cancer registries across Iran. Five-year survival rates were estimated by applying relative survival approaches. We also applied the international cancer survival standard weights for age standardization. Finally, we calculated the excess hazard ratio (EHR) for each province adjusted for age, sex, and cancer sites to estimate the excess hazard ratio of mortality compared to the capital province (Tehran). ResultsThe largest gap in survival was observed in more curable cancer types, including melanoma (41.4%), ovary (32.3%), cervix (35.0%), prostate (26.7%), and rectum (21.4%), while the observed geographical disparity in lethal cancers such as lung, brain, stomach, and pancreas was less than 15%. Compared to Tehran, we found the highest excess hazard of death in Western Azerbaijan (EHR=1.60, 95% CI 1.51, 1.65), Kermanshah (EHR=1.52, 95% CI=1.44, 1.61), and Kerman (EHR=1.46, 95% CI=1.38, 1.53). The hazard ratio of death was almost identical in Isfahan (EHR=1.04, 95% CI=1.03, 1.06) and Tehran provinces. ConclusionProvinces with higher HDI had better survival rates. IRANCANSURV study showed regional disparities in cancer survival in Iran. Cancer patients in provinces with a higher Human Development Index (HDI) had a higher survival rate and lived longer compared to the patients in provinces with medium and low HDI regions.

The Pediatric Proton and Photon Therapy Comparison Cohort: Study Design for a Multicenter Retrospective Cohort to Investigate Subsequent Cancers After Pediatric Radiation Therapy

The physical properties of protons lower doses to surrounding normal tissues compared with photons, potentially reducing acute and long-term adverse effects, including subsequent cancers. The magnitude of benefit is uncertain, however, and currently based largely on modeling studies. Despite the paucity of directly comparative data, the number of proton centers and patients are expanding exponentially. Direct studies of the potential risks and benefits are needed in children, who have the highest risk of radiation-related subsequent cancers. The Pediatric Proton and Photon Therapy Comparison Cohort aims to meet this need. We are developing a record-linkage cohort of 10,000 proton and 10,000 photon therapy patients treated from 2007 to 2022 in the United States and Canada for pediatric central nervous system tumors, sarcomas, Hodgkin lymphoma, or neuroblastoma, the pediatric tumors most frequently treated with protons. Exposure assessment will be based on state-of-the-art dosimetry facilitated by collection of electronic radiation records for all eligible patients. Subsequent cancers and mortality will be ascertained by linkage to state and provincial cancer registries in the United States and Canada, respectively. The primary analysis will examine subsequent cancer risk after proton therapy compared with photon therapy, adjusting for potential confounders and accounting for competing risks. For the primary aim comparing overall subsequent cancer rates between proton and photon therapy, we estimated that with 10,000 patients in each treatment group there would be 80% power to detect a relative risk of 0.8 assuming a cumulative incidence of subsequent cancers of 2.5% by 15 years after diagnosis. To date, 9 institutions have joined the cohort and initiated data collection; additional centers will be added in the coming year(s). Our findings will affect clinical practice for pediatric patients with cancer by providing the first large-scale systematic comparison of the risk of subsequent cancers from proton compared with photon therapy.

Impact of the adjuvant management and risk factors on survival in FIGO stage 3 endometrial cancer patients.

Patients with FIGO stage III endometrial cancer routinely receive adjuvant therapy. The purpose of this study was to evaluate overall survival (OS) and disease-free survival (DFS) in patients with stage IIIA to IIIC2 patients by treatment modality received and risk factors. Patients with stage III endometrial cancer treated from 2000-2010 were identified in the provincial cancer registry. Clinicopathologic characteristics, adjuvant treatments and outcomes were compared using descriptive and multivariable analyses. 261 patients had stage 3 endometrial cancer, 132 with stage IIIA, 9 with IIIB, 85 with IIIC1 and 35 with IIIC2. 39 had FIGO grade 1 disease; 73, grade 2; 147, grade 3. 160 had endometrioid and 35 had serous carcinoma. 161 patients received sequential adjuvant chemotherapy (CT) and radiotherapy (RT); 33 received RT only; 32 received CT only; 35 received neither. 5-year (5Y) DFS and OS were similar among stage IIIA (DFS 46.7%, OS 58.5%), IIIB (DFS 50.8%, OS 58.5%), IIIC1 (DFS 44%, OS 49.9%) and IIIC2 (DFS 42%, OS 41.6%). Use of adjuvant RT was associated with improved median DFS (53.7 vs 14.7m, p<0.00001) and OS (61.9 vs 25.7m, p<0.00001) compared to no RT. Likewise, use of adjuvant CT was also associated with improved DFS (54.8 vs 16.5m, p<0.00001) and OS (62.9 vs 26.5m, p<0.00001) compared to no CT. Those who received both chemotherapy and radiotherapy had better outcomes with 5-year DFS (58.3%) and OS (65.2%), compared with those who received monotherapy. On multivariate analysis, grade 3 disease, deep myometrial invasion >50%, and no adjuvant RT or CT were identified as adversely impacting DFS and OS. In stage III endometrial cancer patients, use of both chemotherapy and radiation therapy was associated with improved DFS and OS and therefore should be recommended in all eligible patients after resection.

A154 CANCERS ASSOCIATED WITH INFLAMMATORY BOWEL DISEASE IN CANADA: A POPULATION-BASED ANALYSIS OF CASES AND MATCHED CONTROLS

Abstract Background Individuals with inflammatory bowel disease (IBD) are known to have a higher risk of digestive tract cancers and cancers associated with immunosuppression. As the IBD population is ageing, age-related cancers may be more commonly diagnosed. Purpose To assess whether IBD patients were at a higher odds of incident cancers than their matched controls stratified by age above and below 65 years. Method A population-based surveillance study was conducted in Alberta, Canada (April 1, 2002 to March 30, 2018). A validated algorithm identified cases of IBD. Each case was age and sex matched to up to 10 non-IBD cases from the general population and linked to the Alberta provincial cancer registry to extract pathology-confirmed incident cancer. Controls were removed if they were not residents of Alberta at the time the matched case was diagnosed with IBD. Only incident cancers diagnosed after the diagnosis of IBD (or matched indexed date for controls) were considered. Age was calculated based on year of inclusion in the cohort or, if applicable, the year of cancer diagnosis. Cancer diagnoses were classified: bladder, biliary and liver, breast, cervix, colorectal, endometrium, gastrointestinal, gynecological, head and neck, hematological, kidney, lung, melanoma, neurological, non-melanoma, pancreas, prostate, renal and bladder, small intestine, thyroid, and miscellaneous. Odds ratios (OR), with 95% confidence intervals (CI), compared IBD cases to matched controls using conditional logistic regression. Stratified analysis at age 65 (&amp;lt;65 and ≥65) was done for all cancers. Result(s) Overall, 3695 incident cancers were diagnosed among 35,763 individuals with IBD as compared to 22,687 cancers among 289,212 controls (OR:1.12; 95%CI: 1.08, 1.16). Those less than 65 years old were at higher odds of developing cancer (1.20; 95%CI: 1.15, 1.26) than those ≥65 (0.97; 95%CI: 0.90, 1.04). Those with IBD had a higher odds biliary and liver (7.41; 95%CI: 5.58, 9.84) and gastrointestinal (2.26; 95%CI: 2.06, 2.48), which including: colorectal (1.78; 95%CI: 1.57, 2.02), pancreas (7.79; 95%CI: 5.53, 10.97), and small intestine (6.59; 95%CI: 4.65, 9.35). Melanoma and non-melanoma, head and neck, and thyroid cancers did not have an increased odds but hematological, lung, neurological, and kidney cancers did show an increased odds among those with IBD. Cancers outside of the gastrointestinal tract were at a lower odds for IBD patients, including: bladder (0.68; 95%CI: 0.54, 0.87), breast (0.72; 95%CI: 0.64, 0.81), gynecological (incl. cervix (0.68; 95%CI: 0.61, 0.78) and endometrium (0.48; 95%CI: 0.34, 0.66), and prostate (0.64; 95%CI: 0.57, 0.73). Image Conclusion(s) Under the age of 65, individuals with IBD have a higher odds of being diagnosed with cancer than the general population, with cancers of the digestive tract driving this association across the age spectrum. Healthcare providers should be aware of higher occurrence of hematological, neurological, lung and renal cancers in those with IBD. Please acknowledge all funding agencies by checking the applicable boxes below CIHR Disclosure of Interest S. Coward: None Declared, S. Murthy: None Declared, H. Singh Consultant of: Pendopharm, Amgen Canada, Bristol Myers Squibb Canada, Roche Canada, Sandoz Canada, Takeda Canada, and Guardant Health, Inc., E. Benchimol Consultant of: Hoffman La-Roche Limited and Peabody &amp; Arnold LLP for matters unrelated to medications used to treat inflammatory bowel disease and McKesson Canada and the Dairy Farmers of Ontario for matters unrelated to medications used to treat inflammatory bowel disease., E. Kuenzig: None Declared, G. Kaplan Grant / Research support from: Ferring, Janssen, AbbVie, GlaxoSmith Kline, Merck, and Shire, Consultant of: Gilead, Speakers bureau of: AbbVie, Janssen, Pfizer, Amgen, and Takeda

Selection Bias in Real-World Data Studies Used to Support Health Technology Assessments: A Case Study in Metastatic Cancer.

Real-world evidence has been increasingly used to support evaluations of emerging therapies. These investigations are often conducted in settings that may not be representative of the underlying population. The purpose of this investigation was to empirically quantify the magnitude of this selection bias. Individuals diagnosed with solid metastatic cancer in Alberta, Canada, between 2010-2019 were identified using the provincial cancer registry for 13 common metastatic sites. Two outcomes used to support oncology reimbursement decisions were examined: the proportion of individuals who initiated systemic therapy and median overall survival (OS). These outcomes were assessed in the entire population and in a subset of individuals who were referred to a medical oncologist. Among the 23,152 individuals in the entire population, 40.8% (95% CI: 40.2-41.4) initiated systemic therapy, and the median OS from diagnosis was 5.4 months (95% CI: 5.3-5.6). Among those who were referred to a medical oncologist (n = 13,372; 57.8%), 67.4% (95% CI: 66.6-68.2) initiated systemic therapy, and the median OS from diagnosis was 11.2 months (95% CI: 10.9-11.5). The magnitude of bias varied by cancer site where lower referral rates were associated with greater bias. Non-referral is an important source of selection bias in real-world investigations. Studies that rely on limited-catchment real-world data should be interpreted with caution, particularly in metastatic cancer settings.

Head-to-head comparison of FOLFIRINOX versus gemcitabine plus nab-paclitaxel in advanced pancreatic cancer: a target trial emulation using real-world data

To emulate a hypothetical target trial assessing the effect of initiating 5-fluorouracil, folinic acid, irinotecan, and oxaliplatin (FOLFIRINOX) versus gemcitabine plus nab-paclitaxel (GN) within 8 weeks of diagnosis on overall survival. An observational cohort study was conducted using population-level data from Alberta, Canada. Individuals diagnosed with advanced pancreatic cancer between April 2015 and December 2019 were identified through the provincial cancer registry and followed until March 2021. Records were linked to other administrative databases containing information on relevant variables. Individuals were excluded if they did not have adequate hemoglobin, platelet, white blood cell, and serum creatinine measures or if they received prior therapy. The observational analog of the per-protocol effect was estimated using inverse probability weighted Kaplan-Meier curves with bootstrapped 95% confidence intervals. Four hundred seven individuals were eligible. The weighted median overall survival was 8.3 months (95% CI, 5.7-11.9) for FOLFIRINOX and 5.1 months (95% CI: 4.3 to 5.8) for GN. The adjusted difference in median overall survival was 3.2 months (95% CI, 1.1-7.4) and the mortality hazard ratio was 0.78 (95% CI, 0.61-0.97). Our estimates favored the initiation of FOLFIRINOX over GN with respect to overall survival.

S45 Cancers Associated With Inflammatory Bowel Disease: A Population-Based Case-Control Study

Background: Individuals with inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), are known to have a higher risk of digestive tract cancers as compared to the general population. As the IBD population has gotten older over time, age-related cancers may be more commonly diagnosed. We conducted a population-based study to assess whether incident cancers were being diagnosed more commonly overtime and whether those with IBD were more likely to be diagnosed with cancer. Methods: A population-based surveillance case-control study was conducted in in Alberta, Canada from April 1, 2002 to March 31, 2018. A validated coding algorithm identified all cases of IBD stratified by type of IBD (CD, UC). Each case was age and sex matched to 10 non-IBD cases from the general population, and then linked to the Alberta provincial cancer registry to extract pathology-confirmed incident cancer. Cancer diagnoses were classified: colorectal, small bowel, pancreatic, biliary and liver, breast, cervical, endometrial, thyroid, hematological, lung, neurological, melanoma, non-melanoma skin cancer, prostate, renal, and bladder. Odds ratios (OR), with 95% confidence intervals (CI), compared IBD cases to matched controls using conditional logistic regression. The annual incidence of cancer diagnosis among the at-risk prevalent IBD population was determined with the average annual percentage change (AAPC) calculated using log binomial regression. Results: Overall, 3,695 incident cancers were diagnosed among 35,763 individuals with IBD as compared to 31,365 cancers among 362,248 controls (IBD: OR = 1.22; 95% CI: 1.18, 1.27; CD: OR = 1.42, 95% CI: 1.34, 1.49; UC: OR = 1.13 95% CI: 1.06, 1.20). Annual incident cancers in those with IBD steadily increased by 3.4% per year (AAPC = 3.44%; 95% CI: 2.71%, 4.18%). A higher odds of cancer was observed across digestive tract cancers for those with IBD: biliary and liver (IBD: OR = 7.76; 95% CI: 5.89, 10.22); colorectal cancer (IBD: OR = 1.88; 95% CI: 1.67, 2.15); small bowel (CD: OR = 10.81; 95% CI: 6.89, 16.95; UC: OR = 1.74; 0.73, 4.16); and pancreas (IBD: OR = 8.01; 95% CI: 5.72, 11.20). Outside of the digestive tract the following cancers were more common in those in IBD: hematological (IBD: OR = 1.47, 95% CI: 1.29, 1.67); lung (IBD: OR = 4.16; 95% CI: 3.59, 4.81); neurological (IBD: OR = 4.73; 95% CI: 3.12, 7.18; and renal (IBD: OR = 2.18; 95% CI: 1.77, 2.68). Non-melanoma skin cancers were associated with IBD (OR = 1.11; 95% CI: 1.05, 1.18), but not melanoma (OR = 0.98; 95% CI: 0.82, 1.18). Other solid-organ cancers were not associated or occurred less commonly in those with IBD: prostate (OR = 0.68; 95% CI: 0.60, 0.77); bladder (OR = 0.73; 95% CI: 0.57, 0.92), cervix (OR = 0.83; 95% CI: 0.73, 0.93), endometrium (OR = 0.50; 95% CI: 0.36, 0.70), and thyroid (OR = 0.84; 95% CI: 0.65, 1.10). Conclusion(s): Over time, persons with IBD are being more commonly diagnosed with cancer. Individuals with IBD are more likely to be diagnosed with cancer as compared to the general population with cancers of the digestive tract driving this association. Healthcare providers should be aware of higher occurrence of hematological, neurological, lung and renal cancers in those with IBD.

Incidence and survival of primary central nervous system tumors diagnosed in 4 Canadian provinces from 2010 to 2015.

The Brain Tumor Registry of Canada was established in 2016 to enhance infrastructure for surveillance and clinical research on Central Nervous System (CNS) tumors. We present information on primary CNS tumors diagnosed among residents of Canada from 2010 to 2015. Data from 4 provincial cancer registries were analyzed representing approximately 67% of the Canadian population. Age-standardized incidence rates (ASIR) and 95% confidence intervals (CI) were calculated using the 2011 Canadian population age distribution. Net survival was estimated using the Pohar-Perme method. A total of 31 644 primary tumors were identified for an ASIR of 22.8 per 100 000 person-years. Nonmalignant tumors made up 47.1% of all classified tumors, with mixed behaviors present in over half of histology groupings. Unclassified were 19.5% of all tumors. The most common histological subtypes are meningiomas (ASIR = 5.5 per 100 000 person-years); followed by glioblastomas (ASIR 4.0 per 100 000 person-years). The overall 5-year net survival rate for CNS tumors was 65.5%; females 70.2% and males 60.4%. GBMs continue to be the most lethal CNS tumors for all sex and age groups. The low annual frequency of most CNS tumor subtypes emphasizes the value of population-based data on all primary CNS tumors diagnosed among Canadians. The large number of histological categories including mixed behaviors and the proportion of unclassified tumors emphasizes the need for complete reporting. Variation in incidence and survival across histological groups by sex and age highlights the need for comprehensive and histology-specific reporting. These data can be used to better inform research and health system planning.

External Validation of the FLIPI Risk Score Measured at Initial Diagnosis and POD24 Among Previously Treated Individuals with Progressed Follicular Lymphoma in Alberta, Canada

Introduction: A number of variables have been shown to predict survival outcomes in follicular lymphoma (FL), including the Follicular Lymphoma International Prognostic Index (FLIPI) score measured at initial diagnosis and progression of disease within 24 months (POD24). However, there exists little research aimed at informing prognosis in a cohort comprised exclusively of FL patients whose disease has relapsed after prior therapy. To address this gap, we assessed the FLIPI score measured at diagnosis and POD24 with respect to their ability to stratify survival outcomes measured from the time of first progression in a group of individuals with FL who experienced disease progression after initial treatment. Methods: An external validation of the FLIPI score measured at diagnosis and POD24 was conducted using population-level data from Alberta, Canada. The study cohort was comprised of individuals diagnosed with FL between 2004-2010 who received either systemic therapy and/or radiation within 180 days of diagnosis and who subsequently had disease progression. Individuals were followed until death or last-known contact with the healthcare system. Relevant data were identified through record linkage of the provincial cancer registry and electronic medical records along with a manual chart review conducted by trained medical doctors. Outcomes were examined from the time of first progression and included time to death (OS), time to death after first progression or second progression (PFS2), and time to death or initiation of third line treatment (TTNT2). For each outcome, Kaplan-Meier curves were estimated stratified by FLIPI and by POD24. To quantify the degree of separation of the Kaplan-Meier curves, we estimated hazard ratios (HRs) using a Cox proportional hazards model and Harrell's concordance statistic (c-statistic) for both the FLIPI index and POD24. Results: 910 individuals were diagnosed with FL between 2004-2010, of which 584 received systemic or radiation therapy. 527 individuals initiated front-line therapy within 180 days of diagnosis, of which 216 experienced progression during the follow-up period and were included in these analyses. Among the 216 individuals, 162 (75%) received front-line systemic therapy which was primarily R-CVP (n=57; 35%) or R-CHOP (n=78; 48.1%). From the time of disease progression, median OS was 11.7 years (95% CI: 8.9-NA). POD24 status was available for all 216 individuals, with 90 (42%) individuals having evidence of progression of disease within 24 months of initiating front-line therapy (POD24+). Overall, 129 of the 216 (60%) individuals had complete information required to derive the FLIPI risk score with 43 (33%) being classified as high-risk, 46 (36%) intermediate-risk, and 40 (31%) low-risk. OS estimates stratified by FLIPI score and by POD24 are presented in Table 1. POD24 was not highly predictive of OS from the time of disease progression (c-statistic: 0.55; HR [POD24+ vs. POD24-]: 1.42; 95% CI: 0.93 to 2.15; p = 0.10). Conversely, the FLIPI score measured at diagnosis was highly predictive of OS from the time of disease progression (c-statistic 0.70; HR [High vs. Low]: 7.38; 95% CI: 3.05 to 17.88, p < 0.01; HR [Int. vs. Low]: 3.70; 95% CI: 1.51 to 9.10, p < 0.01; ; HR [High vs. Int.]: 1.99; 95% CI: 1.15 to 3.47, p = 0.01; Figure 1). These findings were similar when examining PFS2 and TTNT2. In sensitivity analysis, findings were similar when restricting to individuals who received front-line systemic therapy. In addition, the classification of individuals by both POD24 and FLIPI did not meaningfully improve discrimination over FLIPI alone. Conclusions: The FLIPI score measured at initial diagnosis can be used for risk stratification at the time of disease progression among previously treated FL patients. In contrast, POD24 was not highly predictive of survival outcomes from the time of disease progression within this population of FL patients who all had disease progression. Future research is needed to determine if the prognostic utility of the FLIPI risk score measured at initial diagnosis can be improved upon by incorporating variables assessed at the time of relapse. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Definitive Chemoradiotherapy vs. Trimodal Therapy for Locally Advanced Esophageal or Junctional Adenocarcinoma

<h3>Purpose/Objective(s)</h3> Randomized trials have not found trimodal therapy to improve overall survival (OS) compared to definitive chemoradiotherapy for esophageal cancer, but these studies were small and included few adenocarcinoma cases. We sought to compare OS between trimodal therapy and definitive chemoradiotherapy for locally advanced adenocarcinoma of the esophagus and gastroesophageal junction. <h3>Materials/Methods</h3> Patients with locally advanced esophageal or junctional adenocarcinoma undergoing either definitive trimodal therapy or chemoradiotherapy between 2004 and 2018 were retrospectively identified in the provincial cancer registry. The primary analysis was based on intention to treat as determined by chart review (trimodal therapy or definitive chemoradiotherapy). A per-protocol analysis was also completed, wherein patients not undergoing surgery were excluded from the trimodal group, and patients not receiving radiotherapy to at least 41.4 Gy in 23 fractions were excluded from both groups. Kaplan-Meier curves and the Cox proportional hazard model with covariates of age, sex, stage, chemotherapy regimen, and EQD2 (α/β = 4.0) were used to compare OS. <h3>Results</h3> A total of 484 patients were eligible for analysis with a median follow-up of 39.1 months. Median age was 62 with a preponderance of males (87%). Most patients with a clinical AJCC 8th edition stage were stage III (71%), followed by stage IV (21%). The most common dose fractionation schedule was 41.4 Gy in 23 fractions (74%), and the most common chemotherapy regimen was carboplatin/paclitaxel (78%). At the outset, 428 were planned for trimodal therapy and 56 were planned for definitive chemoradiotherapy. There were 67 patients (16%) planned for trimodal therapy who did not undergo surgery, and 15 patients (3%) did not receive at least 41.4 Gy in 23 fractions. By intention to treat, median survival was 24.1 months for trimodal therapy and 21.9 months for definitive chemoradiotherapy. Per protocol, median survival was 30.9 months for trimodal therapy compared to 28.2 months for definitive chemoradiotherapy. No difference in OS was detected either by intention to treat (Cox HR: 0.81; 95% CI: 0.52-1.26; p=0.4) or per protocol (Cox HR: 0.72; 95% CI: 0.42-1.24; p=0.2). <h3>Conclusion</h3> No difference in OS was detected between trimodal therapy and definitive chemoradiotherapy. Our HR was more favorable for definitive chemoradiotherapy than previous retrospective studies on esophageal adenocarcinoma, possibly reflecting the use of treatment intent to account for trimodal patients who fail to undergo surgery. These findings suggest that definitive chemoradiotherapy may be an alternative to trimodal therapy for selected patients after weighing any potential of trimodal therapy prolonging survival against operative morbidity, operative mortality risk, and cost, but further studies including randomized controlled trials are required.

Incidence and mortality of gastric cancer in 2018 and their trends from 2010 to 2018 in Henan Province, China: results from a provincial population-based cancer registry.

BackgroundEndoscopic screening program was carried out in Henan Province, China to reduce the large gastric cancer burden, and its effect evidence is insufficient. Knowledge on current status and time-trend of gastric cancer is need for policy makers to optimize the strategy of gastric cancer control.MethodsGastric cancer data were pooled from registries in the Henan Cancer Registration System which may reflect the whole province cancer incidence and mortality. The pooled registration data, stratified by area (urban/rural), gender, and age groups, was combined with the provincial population data to estimate the incidence and mortality of gastric cancer in Henan Province. The Segi’s world standard population was applied to calculate the age-standardized rate. Joinpoint regression was used to analyze the time-trend in the incidence and mortality.ResultsGastric cancer was diagnosed in 33,971 patients in 2018, ranking second among all cancers. The crude incidence and age-standardized incidence rate (ASIRW) per 100,000 population were 31.15 and 23.05, respectively. In 2018, there were an estimated 25,921 gastric cancer-related deaths, ranking second among all cancer-related deaths. The crude mortality rate and age-standardized mortality rate by world standard population (ASMRW) were respectively 23.77 and 16.80 per 100,000 population. Gender and geographical differences were observed. Notably, the ASIRW and ASMRW were higher in males than females and higher in rural areas than urban areas. For ASIRW and ASMRW, the male to female ratio was 2.50 and 2.71, respectively, and the rural to urban ratio was 1.23 and 1.24, respectively. Declines in the incidence [average annual percent change (AAPC): −3.9%, P=0.001] and mortality (AAPC: −3.1%, P=0.004) of gastric cancer were observed in rural areas due to declines in the incidence and mortality among residents aged 40–69 years. The overall trend of ASIRW and ASMRW were observed to decline with AAPCs of −3.5% (P=0.003) and −2.8% (P=0.007), respectively.ConclusionsGastric cancer incidence and mortality decreased in Henan Province, China, from 2010 to 2018, which may due to the implementation of endoscopic screening for gastric cancer in rural areas. The disease burden, however, remains high, and screening strategies and measures to reduce it should be strengthened.

Harnessing the power of data linkage to enrich the cancer research ecosystem in Canada.

ObjectivesWe will enrich the cancer research ecosystem in Canada through linking cancer registry and administrative health data to the Canadian Partnership for Tomorrow’s Health (CanPath) cohort and biobank. CanPath is Canada’s largest population health study, including 1% of the Canadian population, which seeks to investigate cancer development.&#x0D; ApproachWe are achieving record-level linkage of the CanPath harmonized dataset to provincial cancer registry data, and hospitalization and ambulatory care data from the Canadian Institutes of Health Information (CIHI). The CanPATH harmonized dataset includes comprehensive genetics, environment, lifestyle, and behaviour data. Our linkage activities will result in interprovincial data sharing, with centrally-held linked data, a first in Canadian history. We will demonstrate the CanPath-cancer registry-CIHI linkage potential by investigating the impact of the COVID-19 pandemic on healthcare utilization and outcomes among those with cancer.&#x0D; ResultsThe linkage is ongoing and anticipated to be completed by September 2022. Linked data will be made available through the CanPath Data Safe Haven, a cloud-based solution that meets the legal requirements of the data sharing agreements and provincial privacy policies, and is accessible to researchers through secure access. The CanPath Data Safe Haven will be a federated data platform for Canadian researchers to access, analyze, and contribute research in a collaborative environment. By linking these datasets, this project will: address concerns related to accessibility of cancer data in Canada; bring more value to existing data; support an enhanced understanding of the impacts of cancer on marginalized populations; and create a more integrated approach to cancer data access and management.&#x0D; ConclusionCanPath will be the first program in Canadian history to combine the wealth of cohort resources with cancer registry and administrative health data in a central location at a national scale. We will provide a single point of access for researchers to conduct novel investigations into cancer development and outcomes.

Ambient air pollution and prostate cancer risk in a population-based Canadian case-control study.

Background:Ambient air pollution is a human carcinogen and a possible risk factor for prostate cancer.Methods:We investigated associations between ambient concentrations particulate matter 2.5 (PM2.5) and nitrogen dioxide (NO2) and incident prostate cancer in a Canadian case-control study. Between 1994 and 1997, cases were identified from provincial cancer registries, and a population-based series of controls was recruited. Among men 50 years of age or older, risk factor and residential history data (1975 to 1994) were collected from 1,420 prostate cancer cases and 1,424 controls. Three methods were used to estimate the residential mean exposure to PM2.5 and NO2 during this period: (1) satellite-derived observations; (2) satellite-derived observations scaled with historical fixed-site measurements; and (3) a national land-use regression (LUR) model. Odds ratios (ORs) and their 95% confidence intervals (CIs) in relation to interquartile range (IQR) increases in PM2.5 and NO2 were estimated using logistic regression, adjusting for personal and contextual factors.Results:We found positive associations between exposure to PM2.5 and NO2 over the previous 20 years and prostate cancer. An IQR increase in PM2.5 (3.56 µg/m3 for satellite and 4.48 µg/m3 for scaled satellite observations) yielded ORs of 1.28 (95% CI = 1.07, 1.52) and 1.20 (95% CI = 1.03, 1.40), respectively. For NO2, IQR increases (1.45 ppb for satellite, 15.18 ppb for scaled satellite-derived information, and 15.39 ppb for the national LUR) were associated with ORs of 1.09 (95% CI = 0.95, 1.24), 1.21 (95% CI = 1.02, 1.43), and 1.19 (95% CI = 1.03, 1.38), respectively.Conclusions:Our findings support the hypothesis that ambient air pollution increases the risk of prostate cancer.