Randomized Phase II Trial of Sapanisertib ± TAK-117 vs. Everolimus in Patients With Advanced Renal Cell Carcinoma After VEGF-Targeted Therapy.

BACKGROUND: Sapanisertib, a dual mTORC1/2 inhibitor, may offer more complete inhibition of the PI3K/AKT/mTOR pathway than mTORC1 inhibitors, such as everolimus. This phase II study evaluated the efficacy and safety of single-agent sapanisertib and sapanisertib plus the PI3Kα inhibitor TAK-117, vs. everolimus in patients with advanced clear cell renal cell carcinoma (ccRCC) that had progressed on or after VEGF-targeted therapy. MATERIALS AND METHODS: Patients with histologically confirmed, advanced ccRCC were randomized 1:1:1 to receive single-agent everolimus 10 mg once daily, single-agent sapanisertib 30 mg once weekly, or sapanisertib 4 mg plus TAK-117 200 mg, both once daily for 3 days/week, in 28-day cycles. The primary endpoint was progression-free survival (PFS). RESULTS: Ninety-five patients were treated with everolimus or sapanisertib (n = 32 each), or sapanisertib plus TAK-117 (n = 31). There were no significant differences in PFS among the 3 groups or across any subgroups. Median PFS was 3.8 months with everolimus vs. 3.6 months with sapanisertib (HR, 1.33; 95% CI, 0.75-2.36), and 3.1 months with sapanisertib plus TAK-117 (HR, 1.37; 95% CI, 0.75-2.52). No significant differences in overall survival were seen among groups. Overall response rate was 16.7%, 0%, and 7.1%, respectively. Discontinuations due to treatment-emergent adverse events were 15.6%, 28.1%, and 29.0%. CONCLUSION: Sapanisertib with or without TAK-117 was less tolerable and did not improve efficacy vs. everolimus in patients with advanced ccRCC who had relapsed after or were refractory to VEGF-targeted therapies. Dual mTORC1/2 inhibition may not be an effective therapeutic approach for these patients.

Fractures and long-term mortality in cancer patients: a population-based cohort study.

We assessed post-fracture mortality in a population-based cohort of 122,045 individuals with cancers. Major fractures (hip, vertebrae, humerus, and forearm) were associated with early and long-term increased all-cause mortality. INTRODUCTION: Currently, there are no population-based data among cancer patients on post-fracture mortality risk across a broad range of cancer diagnoses. Our objective was to estimate the association of fracture with mortality in cancer survivors. METHODS: Using Manitoba Cancer Registry data from the province of Manitoba, Canada, we identified all women and men with cancer diagnosed between January 1, 1987, and March 31, 2014. We then linked cancer data to provincial healthcare administrative data and ascertained fractures after cancer diagnosis and mortality to March 31, 2015. Hazard ratios for all-cause mortality in those with versus without fracture were estimated from time-dependent Cox proportional hazards models adjusted for multiple covariates. RESULTS: The study cohort consisted of 122,045 cancer patients (median age 68 years, IQR 58-77, 49.2% female). During the median follow-up of 5.8 years from cancer diagnosis, we ascertained 7120 (5.8%) major fractures. All fracture sites, except for the forearm, were associated with increased mortality risk, even after multivariable adjustment. Excess mortality risk associated with a major fracture was greatest in the first year after fracture (HR 2.42, 95% CI 2.30-2.54) and remained significant > 5 years after fracture (HR 1.60, 95% CI 1.50-1.70) and for fractures occurring > 10 years after cancer diagnosis (HR 1.93, 95% CI 1.79-2.07). CONCLUSION: Fractures among cancer patients are associated with increased all-cause mortality. This excess risk is greatest in the first year and persists more than 5 years post-fracture; increased risk is also noted for fractures occurring up to and beyond 10 years after cancer diagnosis.

Management of Germ Cell Tumors During the Outbreak of the Novel Coronavirus Disease-19 Pandemic: A Survey of International Expertise Centers.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has become a public health emergency affecting frail populations, including patients with cancer. This poses the question of whether cancer treatments can be postponed or modified without compromising their efficacy, especially for highly curable cancers such as germ cell tumors (GCTs). MATERIALS AND METHODS: To depict the state-of-the-art management of GCTs during the COVID-19 pandemic, a survey including 26 questions was circulated by e-mail among the physicians belonging to three cooperative groups: (a) Italian Germ Cell Cancer Group; (b) European Reference Network-Rare Adult Solid Cancers, Domain G3 (rare male genitourinary cancers); and (c) Genitourinary Medical Oncologists of Canada. Percentages of agreement between Italian respondents (I) versus Canadian respondents (C), I versus European respondents (E), and E versus C were compared by using Fisher's exact tests for dichotomous answers and chi square test for trends for the questions with three or more options. RESULTS: Fifty-three GCT experts responded to the survey: 20 Italian, 6 in other European countries, and 27 from Canada. Telemedicine was broadly used; there was high consensus to interrupt chemotherapy in COVID-19-positive patients (I = 75%, C = 55%, and E = 83.3%) and for use of granulocyte colony-stimulating factor primary prophylaxis for neutropenia (I = 65%, C = 62.9%, and E = 50%). The main differences emerged regarding the management of stage I and stage IIA disease, likely because of cultural and geographical differences. CONCLUSION: Our study highlights the common efforts of GCT experts in Europe and Canada to maintain high standards of treatment for patients with GCT with few changes in their management during the COVID-19 pandemic. IMPLICATIONS FOR PRACTICE: Despite the chaos, disruptions, and fears fomented by the COVID-19 illness, oncology care teams in Italy, other European countries, and Canada are delivering the enormous promise of curative management strategies for patients with testicular cancer and other germ cell tumors. At the same time, these teams are applying safe and innovative solutions and sharing best practices to minimize frequency and intensity of patient contacts with thinly stretched health care capacity.

Role of renin-angiotensin system antagonists in the prevention of bevacizumab- and sunitinib-mediated cardiac dysfunction.

Although anticancer systemic therapy agents clearly lead to improved survival in patients with cancer, these can come at the cost of serious complications including cardiotoxicity. Two types of targeted systemic therapies currently in use for colorectal cancer (CRC) and renal cell cancer (RCC), respectively, include the vascular endothelial growth factor inhibitor bevacizumab (BVZ) and the tyrosine kinase inhibitor sunitinib (SNT). Despite the beneficial effects of BVZ and SNT in improving clinical outcomes in the settings of CRC and RCC, there is an increased risk of cardiac dysfunction. The aim of the present study was to determine whether prophylactic administration of renin-angiotensin system (RAS) inhibitors would attenuate the cardiotoxic side effects of BVZ or SNT in a chronic in vivo murine model. A total of 194 wild-type C57Bl/6 male mice received: 1) 0.9% saline, 2) BVZ (10 mg·kg-1·wk-1), or 3) SNT (40 mg·kg-1·day-1) for 4 wk. Within each arm, mice received daily prophylactic treatment with hydralazine (0.05 mg/ml), aliskiren (50 mg/kg), perindopril (4 mg/kg), or valsartan (2 mg/kg). Although hydralazine effectively lowered blood pressure in BVZ- or SNT-treated mice, it did not prevent left ventricular systolic dysfunction. Prophylactic administration of aliskiren, perindopril, or valsartan prevented adverse cardiovascular remodeling in mice treated with either BVZ or SNT. The addition of RAS antagonists also downregulated expression of phosphorylated p38 and Bcl-2-like 19-kDa interacting protein 3 in SNT-treated mice. In our chronic in vivo murine model, RAS antagonists partially attenuated the development of BVZ- or SNT-mediated cardiac dysfunction. Future clinical studies are warranted to investigate the cardioprotective effects of prophylactic treatment with RAS inhibitors in the settings of CRC and RCC. NEW & NOTEWORTHY In the evolving field of cardio-oncology, bevacizumab and sunitinib improve clinical outcomes in the settings of metastatic colorectal cancer and renal cell cancer, respectively. These anticancer drugs, however, are associated with an increased risk of cardiotoxicity. The prophylactic administration of renin-angiotensin system antagonists is partially cardioprotective against bevacizumab- and sunitinib-mediated cardiac dysfunction.

The effect of statin use on the incidence of prostate cancer: A population-based nested case-control study.

Preclinical studies suggest statins may help prevent prostate cancer (PC), but epidemiologic results are mixed. Many epidemiological studies have relatively short prediagnosis drug exposure data, which may miss some statin use. We completed a nested case-control study investigating the impact of statin use on PC diagnosis and clinically significant PC using data from men aged ≥40 years in the Canadian province of Saskatchewan between 1990 and 2010. Drug exposure histories were derived from a population-based prescription drug database. We used conditional logistic regression to model use of statins as a class and stratified analyses for groups defined by lipophilicity. Clinically significant PC was defined as Gleason score 8-10 OR stage C or D or III or IV at diagnosis. 12,745 cases of PC were risk-set matched on age and geographic location to 50,979 controls. Greater than 90% of subjects had prediagnosis drug exposure histories >15 years. 2,064 (16.2%) cases and 7,956 (15.6%) controls were dispensed one or more statin prescriptions. In multivariable models, ever prescription of statins was not associated with PC diagnosis (OR 0.97; 95% CI 0.90-1.05). Neither lipophilic statins (OR 0.96, 95% CI 0.88-1.04) nor hydrophilic statins (OR 1.06, 95% CI 0.95-1.20) impacted PC diagnosis. There was no effect of the dose or duration of statin use. Diagnosis of clinically significant PC decreased with statin use (OR 0.84, 95% CI 0.73-0.97). Statin use is not associated with overall PC risk, regardless of duration or dose of statin exposure. Statin use is associated with a decreased risk of clinically significant PC.

Risk of colorectal cancer after the diagnosis of prostate cancer: A population-based study.

BACKGROUND: A rigorous assessment of the risk of colorectal cancer (CRC) among prostate cancer (PC) survivors that controls for important confounding factors and competing risks is necessary to determine the risk of CRC in this population and to inform screening guidelines. METHODS: With data from Manitoba, Canada, subjects diagnosed with PC as their first cancer between 1987 and 2009 were age-matched with up to 5 men with no history of invasive cancer on the PC diagnosis date. Subjects were followed to the date of diagnosis of CRC or another cancer, death, emigration, or the study endpoint (December 31, 2009). Competing risk proportional hazards models were used to compare the CRC incidence between those with PC and those without PC with the following model covariates: history of lower gastrointestinal endoscopy, frequency of health care visits, diabetes, and socioeconomic status. Mutually exclusive competing outcomes included CRC, another primary cancer, and death. RESULTS: For a total of 559,081 person-years, 14,164 men with PC and 69,051 men without PC were followed. Men diagnosed with PC had an increased risk of a subsequent diagnosis of CRC (all CRC: hazard ratio [HR], 1.14; 95% confidence interval [CI], 1.02-1.27; rectal cancer: HR, 1.36; 95% CI, 1.09-1.71). The treatment of PC with radiation was associated with an increased risk for rectal cancer (HR, 2.06; 95% CI, 1.42-2.99) in comparison with PC cases not treated with radiation. CONCLUSIONS: The risk of CRC is increased after a diagnosis of PC and is highest for rectal cancer among those treated with radiation. CRC screening should be considered soon after the diagnosis of PC, especially for men planning for radiotherapy.

The advent of precision therapy in gastrointestinal malignancies: Targeting the human epidermal growth factor receptor family in colorectal and esophagogastric cancer.

Until recently, systemic therapy for gastrointestinal malignancies was restricted to relatively noncancer-specific cytotoxic chemotherapy. Over the last 15 years targeted therapies have become available, most notably bevacizumab in the case of advanced colorectal cancer. Unfortunately, there are no predictive biomarkers to guide the use of this agent. In this review article, we describe the advent of "Precision Medicine" (in part, the use of patient-specific molecular markers to inform treatment) in gastrointestinal cancers: The use of monoclonal antibodies targeting epidermal growth factor receptor in advanced colorectal cancer, and human epidermal growth factor receptor 2-neu in advanced esophagogastric cancer. In both instances, biomarkers help in selecting appropriate patients for such treatment.

Impact of age, comorbidity, and polypharmacy on receipt of systemic therapy in advanced cancers: A retrospective population-based study.

INTRODUCTION: Cancer incidence, comorbidity, and polypharmacy increase with age, but the interplay between these factors on receipt of systemic therapy (ST) in advanced cancer has rarely been studied. MATERIALS AND METHODS: A retrospective cohort study was conducted including patients aged ≥18 years diagnosed from 2004 to 2015 with multiple myeloma (MM) (all stages), lung cancer (stage IV), and stage III-IV non-Hodgkin's lymphoma (NHL), breast, colorectal (CRC), prostate, or ovarian cancer in Manitoba, Canada. Clinical and administrative health data were used to determine demographic and cancer characteristics, treatment history, comorbidity (Charlson Comorbidity Index [CCI] and Resource Utilization Band [RUB]), and polypharmacy (≥6 medications). Multivariable logistic regression was used to evaluate variable associations with receipt of ST and interaction with age. RESULTS: In total, 17,228 patients were diagnosed with advanced cancer. Ages were distributed as follows: 7% <50 years, 16% 50-59 years, 26% 60-69, 26% 70-79, 24% ≥80 years. ST was administered to 50% of patients. Increased age, polypharmacy, and comorbidity each independently decreased the likelihood of receiving ST. Significant interaction effects were found between age at diagnosis with stage of cancer and cancer type. Differences in probability of ST by cancer stage converged as age increased. In multivariable analysis, adjusting for covariates, patients with MM had the highest odds and lung cancer the lowest odds to receive ST. The impact of comorbidity and polypharmacy did not differ meaningfully with increasing age. DISCUSSION: Increased age, polypharmacy, and comorbidity were each independently associated with decreased receipt of ST in people with advanced cancers. The impact of comorbidity and polypharmacy did not differ meaningfully with increasing age, while age meaningfully interacted with stage and cancer type.

Measuring the impact of COVID-19 on cancer survival using an interrupted time series analysis.

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

Geographical disparities of rectal cancer local recurrence and outcomes: a population-based analysis.

BACKGROUND: Challenges exist in providing high-quality cancer treatments to populations spread over large geographical areas. Local recurrence of rectal cancer is a complicated clinical problem associated with high morbidity and mortality. OBJECTIVES: objectives of this study were to evaluate population-based rates and predictors of local recurrence of rectal cancer in the Province of Manitoba, Canada, with emphasis on the effects of geography. DESIGN: : This was a population-based retrospective analysis. Administrative data from the Manitoba Cancer Registry and individual patient charts were reviewed. SETTINGS: Patients with stages I to III rectal cancer who underwent surgery with curative intent in Manitoba between 2004 and 2006 were included. MAIN OUTCOME MEASURES: The primary outcome was the development of local recurrence after surgical resection. RESULTS: Three hundred seventy patients with a mean age of 67 years were identified. The 5-year local recurrence rate was 17.4%. In multivariate analysis, relative to Winnipeg residents, rural residents, regardless of where they underwent surgery, had an increased risk of local recurrence (HR, 3.47; 95% CI, 1.74-6.92 for surgery in Winnipeg; HR, 2.98; 95% CI, 1.59-5.57 for surgery in rural Manitoba). The absence of both neoadjuvant radiotherapy and adjuvant chemotherapy was associated with a higher risk of local recurrence. Higher risk of mortality was noted for rural patients (HR, 1.90; 95% CI, 1.24-2.89) and for those who developed local recurrence (HR, 2.01; 95% CI, 1.27-3.19). CONCLUSION: Local recurrence rates for rectal cancer are high in Manitoba. Geography is an important variable, because rural status is associated with higher local recurrence rates and decreased survival. The use of neoadjuvant radiotherapy was an important predictor of lower local recurrence rates. Further initiatives are imperative to identify why rural patients experience differences in outcomes in Manitoba.

Longer waiting times for patients undergoing colorectal cancer surgery are not associated with decreased survival.

BACKGROUND AND OBJECTIVES: Wait times are a growing concern in Canada's publicly-funded healthcare system. We sought to determine if increased wait times for colorectal cancer (CRC) treatments resulted in worse outcomes. METHODS: A population-based retrospective cohort analysis of wait times for CRC patients undergoing major surgical resections in Manitoba, Canada, between 2004 and 2006 was undertaken. Administrative records were utilized to estimate total wait time (TWT), defined as the sum of time from index contact with the healthcare system to diagnosis of CRC (diagnostic wait time [DWT]) and the time from diagnosis to first cancer treatment (treatment wait time [TxWT]). Multivariate Cox regression analysis of 5-year overall survival was performed to determine the effect of TWT quartiles on survival. RESULTS: One thousand six hundred twenty eight patients with stage I-IV CRC underwent major surgery with a median TWT of 95 days. Predictors of lower 5-year survival included advanced age, higher stage, lower economic status, increased medical comorbidity, urgent presentation, living between 101 and 500 km from the Provincial cancer center, and not receiving adjuvant chemotherapy. After controlling for these variables, TWT quartiles were not associated with survival (P = 0.4898). CONCLUSIONS: On a population basis, increased TWT was not associated with worse survival, while controlling for important confounders.

Does geography influence the treatment and outcomes of colorectal cancer? A population-based analysis.

BACKGROUND: The Canadian province of Manitoba covers a large geographical area but only has one major urban center, Winnipeg. We sought to determine if regional differences existed in the quality of colorectal cancer care in a publicly funded health care system. METHODS: This was a population-based historical cohort analysis of the treatment and outcomes of Manitobans diagnosed with colorectal cancer between 2004 and 2006. Administrative databases were utilized to assess quality of care using published quality indicators. RESULTS: A total of 2,086 patients were diagnosed with stage I to IV colorectal cancer and 42.2% lived outside of Winnipeg. Patients from North Manitoba had a lower odds of undergoing major surgery after controlling for other confounders (odds ratio (OR): 0.48, 95% confidence interval (CI): 0.26 to 0.90). No geographic differences existed in the quality measures of 30-day operative mortality, consultations with oncologists, surveillance colonoscopy, and 5-year survival. However, there was a trend towards lower survival in North Manitoba. CONCLUSION: We found minimal differences by geography. However, overall compliance with quality measures is low and there are concerning trends in North Manitoba. This study is one of the few to evaluate population-based benchmarks for colorectal cancer therapy in Canada.

Impact of Cancer-Related Virtual Visits on Travel Distance, Travel Time, and Carbon Dioxide (CO2) Emissions during the COVID-19 Pandemic in Manitoba, Canada.

CancerCare Manitoba (CCMB) introduced virtual visits at the beginning of the COVID-19 pandemic to replace many in-person visits. This study examines the impact of virtual visits for cancer care on travel distance, travel time, and carbon dioxide (CO2) emissions. We included all visits to CCMB for invasive and in situ cancers from 1 April 2020 to 31 December 2022. Data were extracted from CCMB's electronic health record. The percentage of visits done virtually by month was reported by age, gender, cancer diagnosis, and regional health authority of residence. Postal codes for patients' residences and clinic locations were converted into latitude and longitude values. Travel distance, travel time, and CO2 emissions associated with travel were estimated. The percentage of virtual visits was highest during the months when COVID-19 restrictions were present in Manitoba and represent more than 50% of such monthly visits. Virtual visits increased with age, were highest among men with urogenital cancer, and were lowest among northern Manitoba residents. The median travel time per visit ranged from 30 min in Winnipeg to 15 h in the Northern Region. The estimated travel distance saved varied from 420,000 to 750,000 km per month. Estimated travel time saved varied from 5500 to 9600 h per month. Estimated CO2 emissions prevented varied from 87 to 155 metric tons per month. Virtual care is an important tool for better supporting those living with cancer by substantially decreasing travel distance and time. Virtual care also contributes to reducing greenhouse gas emissions.

Prostate Cancer Metastasis to Stomach: A Case Report and Review of Literature.

Metastatic prostate cancer is a common diagnosis with a protracted but terminal course. Gastrointestinal (GI) tract involvement is extremely rare, and reportedly portends a poor prognosis. It can present years after the initial prostate cancer diagnosis. Only fifteen cases of prostate cancer metastasis to the stomach have been reported in the literature. We report a case of a 72-year-old man with metastatic castration-resistant prostate cancer and extensive bony involvement. He presented a decade after the diagnosis of prostate cancer with signs of heartburn; a gastric biopsy was initially believed to represent primary gastric carcinoma, but subsequently a diagnosis of prostate cancer metastatic to the stomach was confirmed. This case highlights the importance of the provision of a pertinent clinical history and clinical differential diagnosis at the time of submission of surgical pathology specimens, as well as highlighting the need to have a low index of suspicion to pursue additional pathologic markers whenever a presumed second adenocarcinoma is noted in the context of a patient having a history of current or prior advanced-stage adenocarcinoma of another site. The correct diagnosis can shield the patient from the morbidity of inappropriate surgical or medical management.

Evaluation of the Impact of the Urgent Cancer Care Clinic on Emergency Department Visits, Primary Care Clinician Visits, and Hospitalizations in Winnipeg, Manitoba.

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

New Cancer Diagnoses Before and During the COVID-19 Pandemic.

Importance: Disruptions to health care during the COVID-19 pandemic may have led to missed cancer diagnoses. It is critical to evaluate the association between the COVID-19 pandemic and cancer incidence to address public and patient anxiety, inform recovery efforts, and identify strategies to reduce the system's vulnerability to future disruptions. Objective: To examine the association between the COVID-19 pandemic and cancer incidence in Manitoba, Canada. Design, Setting, and Participants: A population-based cross-sectional study design was conducted using data from the Manitoba Cancer Registry and an interrupted time-series analysis. All individuals diagnosed with cancer in Manitoba, Canada, from January 1, 2015, until December 31, 2021, were included. Individuals diagnosed with breast, colon, rectal, or lung cancer were grouped by age as follows: younger than 50 years, 50 to 74 years, and 75 years and older. Exposures: COVID-19 pandemic. Main Outcomes and Measures: Age-standardized cancer incidence rates and the estimated cumulative difference between the number of cases in the absence of COVID-19 and observed (fitted) number of cancer cases. Results: A total of 48 378 individuals were included. The median (IQR) age at diagnosis was 68 (59-77) years and 23 972 participants (49.6%) were female. In April 2020, there was a 23% decrease in overall cancer incidence. Cancer incidence decreased by 46% for breast, 35% for colon, 47% for rectal, 50% for head and neck, 65% for melanoma, and 33% for endocrine cancer diagnoses and increased by 12% for hematological cancer diagnoses and 8% for diagnoses of cancers with an unknown primary site. Lung cancer incidence remained stable until December 2020 when it decreased by 11%. Brain and central nervous system and urinary cancer diagnoses decreased consistently over time from April 2020 to December 2021 by 26% and 12%, respectively. No association was observed with gynecologic (1% increase), other digestive (1% decrease), or pancreatic (7% increase) cancer incidence. As of December 2021, Manitoba had an estimated deficit of 692 (5.3%) cancers. The largest estimated deficits were for breast (273 cases, 14.1% deficit), colon (133 cases, 12.2% deficit), and lung cancers (132 cases, 7.6% deficit). Conclusions and Relevance: In this study, the COVID-19 pandemic was associated with an initial decrease in cancer diagnosis incidence followed by a recovery for most cancer sites. However, the cumulative deficit for some cancers with high fatality needs immediate attention.

Cancer incidence during the COVID-19 pandemic by region of residence in Manitoba, Canada: A cancer registry-based interrupted time series study.

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

Adjuvant chemotherapy for stage III colon cancer: does timing matter?

BACKGROUND: Clinical trials commonly mandate that adjuvant chemotherapy for colon cancer should commence within 8 weeks (56 days) of surgery. OBJECTIVE: We investigated the consequences of the timing of adjuvant chemotherapy for stage III colon cancer. PATIENTS AND METHODS: This is a retrospective review of all patients with newly diagnosed stage III colon cancer who received adjuvant chemotherapy in 2 provincial centers in 1999 and 2000. The impact of time to adjuvant chemotherapy on overall survival and relapse-free survival was analyzed by the use of univariate and multivariate Cox modeling, adjusting for prognostic factors. RESULTS: Three hundred forty-five subjects were included. Median time to adjuvant chemotherapy was 50 days (range, 20-242 days); in 111 (32.2%) patients, it was beyond 56 days. On univariate analysis, time >56 days was nonsignificantly associated with a hazard ratio of death of 1.31 (P = .12). Similar results were seen for relapse-free survival. Planned exploratory analysis suggests that the commencement of adjuvant chemotherapy up to 10 weeks postsurgery still confers a benefit. CONCLUSIONS: Delaying adjuvant chemotherapy in stage III colon cancer beyond 8 to 10 weeks postsurgery appears to be associated with diminished benefit.

Feasibility of Randomized Controlled Trials for Cancer Drugs Approved by the Food and Drug Administration Based on Single-Arm Studies.

Background: The US Food and Drug Administration (FDA) introduced an Accelerated Approval (AA) pathway to expedite patient access to new drugs. AA accepts less rigorous trial designs, including single-arm studies (SAS), owing to perceived lack of feasibility of timely randomized controlled trials (RCTs). Methods: We designed hypothetical RCTs with endpoints of overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) for FDA approvals based on SAS for solid tumors during 2010-2019. Existing standards of care served as controls. RCTs were designed to detect a difference with power of 0.80, α-error of 5% (2-sided), and 1:1 randomization. Accrual duration was estimated based on participation by less than 5% of eligible patients derived from cancer-specific incidence and mortality rates in the United States. Results: Of 172 (18.0%) approvals during the study period, 31 (18.0%) were based on SAS. Median sample size was 104 (range = 23-411), and 77.4% were AA. All studies reported ORR, 55% reported duration of response, 19.4% reported PFS, and 22.5% reported OS. Median sample sizes needed to conduct RCTs with endpoints of ORR, PFS, and OS were 206, 130, and 396, respectively. It would have been theoretically possible to conduct RCTs within duration comparable with that required by SAS for 84.6%, 94.1%, and 80.0% of approvals with endpoints of ORR, PFS, and OS, respectively. Conclusion: An overwhelming majority of FDA approvals based on SAS should be feasible as RCTs within a reasonable time frame. Given the collateral harms to patients and to scientific rigor, drug approval based on SAS should only be permitted under exceptional circumstances.

Outpatient oral anticancer agent utilization and costs in Manitoba from 2003 to 2016: a population-based study.

INTERVENTION: In April 2012, the Manitoba Home Cancer Drug Program (HCDP) was introduced to allow 100% coverage for eligible oral anticancer agents (OAA) and supportive medications for Manitobans with cancer requiring these therapies. RESEARCH QUESTIONS: What is the extent of use and cost of OAAs among outpatients in Manitoba from 2003/04 to 2015/16? Did the HCDP change OAA user and prescription patterns? METHODS: This was a retrospective, population-based study using administrative data to measure the prevalence of drug utilization over time and the impact of HCDP on OAA use and prescriptions using generalized linear models. Manitobans with cancer who filled an OAA or supportive medication covered by HCDP from 2003/04 to 2015/16 were included. RESULTS: This study included 22,393 people with cancer who filled an OAA prescription. The prevalence of OAA use increased from 222 per 100,000 to 328 per 100,000 from 2003/04 to 2015/16. Hormone therapy for breast cancer was the most common class of OAA used (increased from 154 per 100,000 to 231 per 100,000). We observed a 2.6-fold decrease in the prevalence of oral alkylating agents and a 10.7-fold increase in the prevalence of protein kinase inhibitors during the study period. The total cost of targeted OAAs per year for all Manitobans with cancer increased from $1.8 million to $19 million. CONCLUSION: We observed an increase in OAA prevalence and the cost of oral targeted chemotherapy is high. Our findings underline the need for addressing these high-cost medications in future developments of a national drug program.

RéSUMé: INTERVENTION: Le Manitoba a introduit en avril 2012 le Programme de médicaments anticancéreux pris à domicile (HCDP en anglais), qui offre un accès entièrement gratuit aux agents anticancéreux oraux (AAO) admissibles et aux médicaments d'appoint aux Manitobains atteints de cancer qui ont besoin de ces traitements. QUESTIONS DE RECHERCHE: Quelle a été l'utilisation des AAO par les malades externes au Manitoba entre 2003-2004 et 2015-2016 et quel en a été le coût? Le programme HCDP a-t-il changé les modes d'utilisation et de prescription des AAO? MéTHODE: Cette étude populationnelle rétrospective a utilisé des données administratives pour mesurer la prévalence de l'utilisation des médicaments au fil du temps et l'incidence du programme HCDP sur l'utilisation et la prescription des AAO à l'aide de modèles linéaires généralisés. Les Manitobains atteints de cancer qui ont fait exécuter une ordonnance pour un AAO ou un médicament d'appoint couvert par le programme HCDP entre 2003-2004 et 2015-2016 ont été inclus. RéSULTATS: L'étude a inclus 22 393 personnes atteintes de cancer ayant fait exécuter une ordonnance d'AAO. La prévalence de l'utilisation des AAO a augmenté, passant de 222 pour 100 000 à 328 pour 100 000 entre 2003-2004 et 2015-2016. L'hormonothérapie pour le cancer du sein a représenté la classe d'AAO la plus communément utilisée (en hausse de 154 pour 100 000 à 231 pour 100 000). Nous avons observé une diminution par un facteur de 2,6 de la prévalence des agents alcoylants oraux et une augmentation par un facteur de 10,7 de la prévalence des inhibiteurs de protéine kinase au cours de la période de l'étude. Le coût total annuel des AAO ciblés pour tous les Manitobains atteints de cancer est passé de 1,8 millions de dollars à 19 millions de dollars. CONCLUSION: Nous avons observé une augmentation de la prévalence des AAO, et le coût des agents chimiothérapeutiques oraux ciblés est élevé. Nos constatations confirment la nécessité d'aborder ces médicaments coûteux dans les versions futures d'un programme de médicaments national.