Examining Treatment Patterns and Real-World Outcomes in Chronic Lymphocytic Leukemia Using Administrative Data in Ontario

Information on the real-world experience of Canadians diagnosed with chronic lymphocytic leukemia (CLL) is limited. This study was conducted to report treatment patterns and outcomes of CLL using Ontario administrative data. A retrospective cohort study was conducted in patients diagnosed with CLL between 1 January 2010 and 31 December 2017 identified in the Ontario Cancer Registry (OCR). Data were accessed using the Institute of Clinical Evaluative Sciences (ICES), which collects various population-level health information. In the Ontario Cancer Registry, 2887 CLL patients receiving treatment and diagnosed between 2010–2017 were identified. Fludarabine, cyclophosphamide and rituximab (FCR) chemoimmunotherapy was most frequently used as a first line, but use declined since ibrutinib and obinutuzumab combinations were funded in 2015. In patients treated with frontline FCR, survival at year one was 89% pre-2015 and 96% post-2015; at year four, survival was 73% and 87%, respectively. Survival in patients treated with frontline chlorambucil was 76% pre-2015 and 75% post-2015 in year 1, and 45% and 56% in year 3. Our analysis shows that, as the treatment landscape for CLL has shifted, use of newer and novel agents as a first line or earlier in the relapsed/refractory setting has resulted in improved survival outcomes.

Utilization of imaging for active surveillance in testicular cancer: Is real-world practice concordant with guidelines?

Introduction: Imaging is an integral component of active surveillance following orchiectomy for stage 1 non-seminoma (NSGCT) and seminoma germ cell tumors. In this population-based study, we describe use of imaging among patients with early-stage testicular cancer and evaluate whether they are concordant with guideline recommendations. Methods: This is a population-based, retrospective cohort study to describe utilization of imaging among all patients with early-stage testicular cancer treated with active surveillance in the Canadian province of Ontario. The Ontario Cancer Registry was linked to electronic records of treatment to identify use of chest and abdomen/pelvis imaging. Data from 2000–-2010 were included with followup for up to five years for patients with non-seminoma and 10 years for patients with seminoma. The key outcome of interest was the frequency of imaging at temporal milestones following orchiectomy. Compared to the most contemporaneous guidelines in Ontario, any discordant frequency of imaging was defined as underutilization or overutilization. Substantial under- or overutilization was defined as >1 imaging test less/more than what was recommended during a 12-month period. Results: The study population included 569 patients with NSGCT (median age 28) and 1107 with seminoma (median age 37). Among patients with NSGCT, adherence with body imaging was low in years 1–3 of surveillance (range 26–37%, predominantly underuse) and higher in years 4–5 (63–67%, predominantly overuse). Adherence with chest imaging was even lower (range 11–34% during years 1–5). Among patients with seminoma, adherence with abdominal and chest imaging was relatively stable and comparable throughout the 10-year followup period (range 23–47% abdomen and 28–47% chest). Multivariable analysis confirmed that underutilization of imaging was more common in recent years. NSGCT histology was associated with underutilization in years 1–2 but overutilization in years 3–5. Conclusions: In routine clinical practice, patients with testicular cancer commonly receive imaging discordant to the protocol for active surveillance, with a substantial proportion receiving both under- and overutilization at various times during surveillance followup.

Decreased Colorectal Cancer Incidence and Incidence-Based Mortality in the Screening-Age Population of Ontario

Background and Aims We aimed to evaluate trends in Ontario, Canada, 2002 to 2016, in uptake of colorectal evaluative procedures, colorectal cancer (CRC) incidence and incidence-based mortality in the colorectal screening-age population. Methods We defined the screening age-eligible population as persons 51 to 74 years of age with ≥1 year eligibility for the Ontario Health Insurance Plan, excluding those with a diagnosis of CRC in the Ontario Cancer Registry (OCR) prior to age 50 or January 1, 2002. We computed annual up-to-date status with colorectal evaluative procedures from billing claims, and CRC incidence from the OCR. In order to compute incidence-based CRC mortality, we included persons with a first diagnosis of CRC between the ages of 51 and 74, diagnosed between January 1, 1992 and December 31, 2001, still alive and <75 years of age on January 1, 2002, based on cause of death from the OCR. Overall, age-stratified and sex-stratified trends were evaluated by Cochran–Armitage trend tests. Results Persons up to date with colorectal evaluative procedures increased from 628,214/2,782,061 (22.6%) in 2002 to 2,584,570/4,179,789 (62.2%) in 2016. CRC incidence fell from 129.3/100,000 in 2002 to 94.54/100,000 in 2016, and incidence-based CRC mortality fell from 40.8/100,000 to 24.1/100,000. Decreasing trends in overall and stratified incidence and mortality were all significant, except among persons 51 to 54 years old. Conclusions There was continued increase in persons up-to-date with colorectal evaluative procedures, and significant decrease in CRC incidence and incidence-based CRC mortality from 2002 through 2016.

Cancer surveillance among workers in plastics and rubber manufacturing in Ontario, Canada

ObjectiveOccupational exposure to agents in plastics and rubber manufacturing has been associated with elevated risk of certain cancers. We sought to evaluate cancer risk among workers employed in occupations and industries with these exposures as part of an ongoing surveillance programme in Ontario, Canada.MethodsThe Occupational Disease Surveillance System (ODSS) cohort was established using workers’ compensation claims data and includes 2.18 million workers employed from 1983 to 2014. Workers were followed for site-specific cancer diagnoses in the Ontario Cancer Registry through 2016. Cox proportional hazard models were used to estimate adjusted HR and 95% CI.ResultsWe identified 81 127 workers employed in plastics and rubber manufacturing industries or materials processing and product fabricating occupations. Compared with all other women in the ODSS, those in materials processing occupations had an elevated rate of lung cancer (HR 1.38, 95% CI 1.20 to 1.58) that was not observed among men. An elevated rate of breast cancer was observed among female labourers (HR 1.36, 95% CI 1.01 to 1.82) and moulders (HR 1.47, 95% CI 0.91 to 2.37) in plastics and rubber product fabricating occupations. Overall, elevated rates were observed for oesophageal, liver, stomach, prostate and kidney cancer in job-specific subgroups, including mixing and blending, bonding and cementing, and labouring. There was little evidence of association for lymphatic or haematopoietic cancers.ConclusionsFindings for lung and breast cancer in women are consistent with other studies and warrant further attention in Ontario. Given the relatively young age at end of follow-up, surveillance in these workers should continue as the cohort ages.

A population-based study of pulmonary monitoring and toxicity for patients with testicular cancer treated with bleomycin

Background Bleomycin is commonly used to treat advanced testicular cancer and can be associated with severe pulmonary toxicity. The primary objective of the present study was to describe the use of pulmonary function tests (pfts) and chest imaging before, during, and after treatment with bleomycin. Methods To identify all incident cases of testicular cancer treated with bleomycin-based chemotherapy in the Canadian province of Ontario during 2005–2010, the Ontario Cancer Registry was linked with chemotherapy treat­ment records. Health administrative databases were used to describe use of pfts, chest imaging, and physician visits for respiratory complaints. Results Of 394 patients treated with orchiectomy and chemotherapy who received at least 1 dose of bleomycin, 93% had complete chemotherapy records available. In the 4 weeks before, during, and within 2 years after finishing bleomycin-based chemotherapy, pfts were performed in 17%, 17%, and 29% of patients respectively. Chest imaging was performed in 68%, 62%, and 98% of patients in the same time periods. In the 2 years after bleomycin-based chemotherapy, 23% of treated patients had a physician visit for respiratory symptoms. That rate was substantially higher for men with greater exposure to bleomycin: 40% (24 of 60) for 10–12 doses bleomycin compared with 21% (53 of 250) for 7–9 doses and with 14% (8 of 58) for 1–6 doses (p = 0.002). Conclusions Quality improvement initiatives are needed to increase baseline rates of chest imaging within 4 weeks of starting chemotherapy for testicular cancer; to understand why such a high proportion of men have chest imaging during bleomycin-based chemotherapy; and to mitigate the excess pulmonary toxicity seen with increasing expos­ure to bleomycin.

Retrospective cohort study of real-world treatment patterns and overall survival in patients with chronic lymphocytic leukemia (CLL) diagnosed between 2010 to 2017 in Ontario, Canada.

e20003 Background: With recent advances in treatment of CLL, it is important to understand emerging treatment patterns and associated outcomes. A population-based study was undertaken to describe the management and survival of CLL patients in Ontario, Canada. Methods: Patients diagnosed with CLL between January 1, 2010 and December 31, 2017 were identified in the Ontario Cancer Registry and linked to provincial administrative databases. Treatment patterns by line of therapy were characterized, including analyses of time to initiation and between therapies. Overall survival was calculated. Results: 2,887 CLL patients were identified (median age 68yr; 67% male). The mean time from diagnosis to first line (1L) treatment was 651 days with 35% of patients receiving fludarabine-cyclophosphamide-rituximab (FCR) based treatment. During the study period, 71% of patients did not yet receive second line (2L) therapy and did not have subsequent follow up, while 19% received 2L ibrutinib. Median time to 2L initiation from 1L treatment discontinuation was 636 days. The table summarizes 1L and 2L therapies. Of the 827 patients on 2L therapy, 65% received ibrutinib. After the introduction of publicly funded novel agents in 2015, a shift in treatment patterns away from FCR and chlorambucil based regimens was observed. Overall mean survival for the cohort from diagnosis was 6.8yrs, and mean 5 year probability of survival was 72.4%. Conclusions: A shift in treatment patterns for CLL can be seen with the introduction of newer therapies, such as ibrutinib. The results can support healthcare decision-makers by characterizing the size of this patient population, real world treatment patterns and survival outcomes for patients with CLL. [Table: see text]

Melanoma nodal management in Ontario the year after the 2012 American Society of Clinical Oncology and Society of Surgical Oncology guideline

Background In 2012 in the United States, the American Society of Clinical Oncology and the Society of Surgical Oncology (asco/sso) published a joint guideline about indications for sentinel lymph node biopsy (slnb) in cutaneous melanoma. The guideline supported completion lymph node dissection (clnd) for all patients with positive sentinel nodes. We examined the rates and predictors of slnb and clnd for melanoma patients in Ontario (population 13.6 million) after publication of that guideline.Methods We used the Ontario Cancer Registry to identify patients diagnosed with cutaneous melanoma in 2013. Patient records were linked to prospectively maintained health administrative databases to obtain details for each patient, including surgical procedures.Results Of the 3298 patients with melanoma identified in Ontario in 2013, 1973 (59.8%) could be analyzed. Most of that group (n = 1227, 62.2%) underwent local excision alone; 746 (37.8%) had a slnb. The slnb was performed in 13.9%, 67.8%, 62.6%, and 47.2% of patients with T1, T2, T3, and T4 primary melanomas respectively. In multivariate analysis, receipt of slnb was positively associated with younger age (<80 years), higher T stage, and a non-head-andneck primary. Of the patients who had a slnb, 136 (18.2%) were found to be node-positive. A clnd was performed in 82 of those patients (60.3%).Conclusions In Ontario, only two thirds of patients with intermediate-thickness melanomas (T2, T3) underwent slnb as recommended by the asco/sso guideline. Use of slnb was less frequent for patients with a head-and-neck primary and higher for younger patients (<80 years). The rate of clnd after a positive slnb was also low relative to the guideline recommendation.

Management of Cancer-Associated Intestinal Obstruction in the Final Year of Life

Background: There is variation in the clinical management of intestinal obstruction (IO) in patients with cancer. We describe the management of cancer-associated IO near the end of life in a population-based cohort with universal health coverage. Methods: Patients who died of gastric, colorectal, ovarian, and pancreatic cancers from 2002 to 2015 were identified from the Ontario Cancer Registry. Those with ≥1 hospital admission for IO in the final year of life were identified from administrative data. Management of IO at index admission was categorized as surgery, gastrostomy, stent, feeding jejunostomy, and medical management. Trends in management over the study period were assessed by the Cochran-Armitage test. Results: The cohort included 57 378 patients (gastric [n = 7448, 13%], colorectal [n = 30 577 53%], ovarian [n = 6273, 11%], and pancreatic [n = 13 080, 23%] cancers). Of those, 7618 (13%) patients had ≥1 admission for IO in the final year of life. Of these patients, 2657 (35%) patients were managed with a surgical/procedural intervention at index admission (surgery [86%], gastrostomy [8%], stent [6%], and jejunostomy [0.4%]); the remaining patients (n = 4961, 65%) received medical management. Over the study period, there was a small but statistically significant increase in the use of stents (0% in 2002 to 5% in 2015, P < .0001) and gastrostomy tubes (2% in 2002 to 4% in 2015, P = .002) and a large decrease in the use of surgery (41% in 2002 to 28% in 2015, P = .04). Conclusions: Management of IO has changed over time with the increased use of stents and gastrostomy tubes and decreased use of surgery.

Melanoma nodal management in Ontario following ASCO/SSO guidelines.

e21054 Background:Methods:Results: Conclusions:The American Society of Clinical Oncology and Society of Surgical Oncology (ASCO/SSO) published a joint guideline in 2012 regarding indications for sentinel lymph node biopsy (SLNB) in cutaneous melanoma. The guideline supported completion lymph node dissection (CLND) for all patients with a positive SLNB. We examined the rates and predictors of SLNB and CLND for melanoma patients in Ontario (population 13.6 million) following guideline publication. Methods: We used the Ontario Cancer Registry (OCR) to identify cutaneous melanoma patients diagnosed in 2013. Patient records were linked to prospectively maintained health administrative databases to obtain details for each patient including surgical procedures. Results: We identified 3298 melanoma patients from Ontario in 2013 of which 1,973 (59.8%) could be analyzed. The majority, 1,227 (62.2%) had a local excision alone, while 746 (37.8%) had a SLNB. SLNB was performed on T1, T2, T3 and T4 primary melanomas in 13.9%, 67.8%, 62.6% and 47.2% of cases respectively. Receipt of a SLNB was positively associated with a younger age (< 80), higher T stage, and non-head and neck primary in multivariate analysis. Of the patients who received a SLNB 136 (18.2%) were found to be node positive. A CLND was performed in 82 (60.3%) of these patients. Conclusions: In Ontario only two-thirds of intermediate thickness melanomas (T2, T3) received a SLNB as recommended by the ASCO/SSO guidelines. Utilization was lower for head and neck patients and higher for younger (< 80 years) patients. Use of CLND for positive SLNB was also low relative to the guidelines.

O6B.2 Cancer risk by ore type in a mixed miners cohort

Background and objectivesMining may involve exposure to many carcinogens, including respirable crystalline silica (RSC), diesel engine exhaust (DEE), nickel (Ni), chromium (Cr), radon (Rn), and arsenic (As), which vary by ore being mined. The province of Ontario, Canada has a diverse mining sector with associated exposures including gold (RSC/DEE/As/Cr), uranium (RSC/DEE/Rn), and nickel-copper (DEE/Ni), and other ores (RSC/DEE). The study aim was to examine the risk of cancer by ore type in a mixed mining cohort.MethodsFrom 1928–1987 workers in the Ontario minerals industry were required to undergo an annual physical examination and chest x-ray, as well as record their mining work history in order to receive certification. Data from these exams was used to create the Mining Master File (MMF) cohort. Cancers were identified through linkage of the MMF with the Ontario Cancer Registry (1964–2017). Cancer risk among miners was compared to provincial rates using Standardized Incidence Ratios (SIR); internal analyses were conducted using Poisson regression.ResultsIndividuals who died or were lost before 1964, had missing or invalid data, or employment of less than two weeks were excluded. Too few women (n=161) were available for analysis. In total, 61 397 men were included in the analysis. Gold miners had excesses of lung (SIR=1.30, 95%CI=1.23–1.38) and nasopharyngeal cancer (SIR=2.34, 95%CI=1.39–3.70). Uranium miners had excesses of lung (SIR=1.57, 95%CI=1.45–1.70), bladder (SIR=1.20, 95%CI=1.02–1.40), and bone (SIR=2.45, 95%CI=1.30–4.19) cancers. Nickel-copper miners had excesses of lung (SIR=1.13, 95%CI=1.08–1.19), bone (SIR=2.02, 95%CI=1.32–2.96), and sinonasal cancer (SIR=1.73, 95%CI=1.12–2.56).ConclusionsIncreased risks for specific cancers were observed among people who mined many different ore types. Most of the associations were as expected, but several (e.g., bone cancers) will undergo further investigation. Future analyses will examine the impact of combined exposures among miners of multiple ore types.