To quantify the association of cancer treatment delay and mortality for each four week increase in delay to inform cancer treatment pathways.
Systematic review and meta-analysis.
Published studies in ...Medline from 1 January 2000 to 10 April 2020.
Curative, neoadjuvant, and adjuvant indications for surgery, systemic treatment, or radiotherapy for cancers of the bladder, breast, colon, rectum, lung, cervix, and head and neck were included. The main outcome measure was the hazard ratio for overall survival for each four week delay for each indication. Delay was measured from diagnosis to first treatment, or from the completion of one treatment to the start of the next. The primary analysis only included high validity studies controlling for major prognostic factors. Hazard ratios were assumed to be log linear in relation to overall survival and were converted to an effect for each four week delay. Pooled effects were estimated using DerSimonian and Laird random effect models.
The review included 34 studies for 17 indications (n=1 272 681 patients). No high validity data were found for five of the radiotherapy indications or for cervical cancer surgery. The association between delay and increased mortality was significant (P<0.05) for 13 of 17 indications. Surgery findings were consistent, with a mortality risk for each four week delay of 1.06-1.08 (eg, colectomy 1.06, 95% confidence interval 1.01 to 1.12; breast surgery 1.08, 1.03 to 1.13). Estimates for systemic treatment varied (hazard ratio range 1.01-1.28). Radiotherapy estimates were for radical radiotherapy for head and neck cancer (hazard ratio 1.09, 95% confidence interval 1.05 to 1.14), adjuvant radiotherapy after breast conserving surgery (0.98, 0.88 to 1.09), and cervix cancer adjuvant radiotherapy (1.23, 1.00 to 1.50). A sensitivity analysis of studies that had been excluded because of lack of information on comorbidities or functional status did not change the findings.
Cancer treatment delay is a problem in health systems worldwide. The impact of delay on mortality can now be quantified for prioritisation and modelling. Even a four week delay of cancer treatment is associated with increased mortality across surgical, systemic treatment, and radiotherapy indications for seven cancers. Policies focused on minimising system level delays to cancer treatment initiation could improve population level survival outcomes.
Despite the widespread increase in the incidence of early-onset colorectal cancer (EoCRC), the reasons for this increase remain unclear. The objective of this study was to determine risk factors for ...the development of EoCRC.
We conducted a systematic literature review and meta-analysis of studies examining non-genetic risk factors for EoCRC, including demographic factors, comorbidities, and lifestyle factors. Random effects meta-analyses were conducted for risk factors that were examined in at least three studies. Heterogeneity was investigated using the Q-test and I
statistic.
From 3304 initial citations, 20 studies were included in this review. Significant risk factors for EoCRC included CRC history in a first-degree relative (RR 4.21, 95% CI 2.61-6.79), hyperlipidemia (RR 1.62, 95% CI 1.22-2.13), obesity (RR 1.54, 95% CI 1.01-2.35), and alcohol consumption (high vs. non-drinkers) (RR 1.71, 95% CI 1.62-1.80). While smoking was suggestive as a risk factor, the association was not statistically significant (RR 1.35, 95% CI 0.81-2.25). With the exception of alcohol consumption, there was considerable heterogeneity among studies (I
> 60%). Other potential risk factors included hypertension, metabolic syndrome, ulcerative colitis, chronic kidney disease, dietary factors, sedentary behaviour, and occupational exposure to organic dusts, but these were only examined in one or two studies.
The results of this study advance the understanding of the etiology of EoCRC. High-quality studies conducted on generalizable populations and that comprehensively examine risk factors for EoCRC are required to inform primary and secondary prevention strategies.
The effect of acute and long-term exposures to outdoor particulate air pollution on lung function in healthy adults is not well established. The objective of this study was to conduct a systematic ...literature review and meta-analysis of studies that assessed the relationship of outdoor particulate air pollution and lung function in healthy adults. Studies that contained data on outdoor air particulate matter levels (PM10 or PM2.5) and forced expiratory volume in 1 s (FEV1) in healthy adults were eligible for inclusion. Effect estimates, in relation to long-term and acute exposures, were quantified separately using random effects models. A total of 27 effect estimates from 23 studies were included in this review. Acute exposures were typically assessed with PM2.5, while long-term exposures were predominantly represented by PM10. A 10 µg/m3 increase in short-term PM2.5 exposure (days) was associated with a −7.02 mL (95% CI −11.75 to –2.29) change in FEV1. A 10 µg/m3 difference in long-term PM10 exposure was associated with a −8.72 mL (95% CI −15.39 to –2.07) annual change in FEV1 and an absolute difference in FEV1 of −71.36 mL (95% CI −134.47 to –8.24). This study provides evidence that acute and long-term exposure to outdoor particulate air pollution are associated with decreased FEV1 in healthy adults. Residual confounding from other risk factors, such as smoking, may explain some of the effect for long-term exposures. More studies are required to determine the relationship of long-term exposure to PM2.5 and short-term exposure to PM10, which may have different biologic mechanisms.
Background
Socioeconomic status (SES) is associated with a range of health outcomes, including cancer diagnosis and survival. However, the evidence for this association is inconsistent between ...countries with and without single‐payer health care systems. In this study, the relationships between neighborhood‐level income, cancer stage at diagnosis, and cancer‐specific mortality in Alberta, Canada, were evaluated.
Methods
The Alberta Cancer Registry was used to identify all primary cancer diagnoses between 2010 and 2020. Average neighborhood income was determined by linking the Canadian census to postal codes and was categorized into quintiles on the basis of income distribution in Alberta. Multivariable multinomial logistic regression was used to model the association between income quintile and stage at diagnosis, and the Fine–Gray proportional subdistribution hazards model was used to estimate the association between SES and cancer‐specific mortality.
Results
Out of the 143,818 patients with cancer included in the study, those in lower income quintiles were significantly more likely to be diagnosed at stage III (odds ratio OR, 1.07; 95% CI confidence interval, 1.06–1.09) or IV (OR, 1.12; 95% CI, 1.11–1.14) after adjusting for age and sex. Lower income quintiles also had significantly worse cancer‐specific survival for breast, colorectal, liver, lung, non‐Hodgkin lymphoma, oral cavity, pancreas, and prostate cancers.
Conclusions
Disparities were observed in cancer outcomes across neighborhood‐level income groups in Alberta, which demonstrates that health inequities by SES exist in countries with single‐payer health care systems. Further research is needed to better understand the underlying causes and to develop strategies to mitigate these disparities.
The association between socioeconomic status and cancer outcomes in countries with single‐payer health care systems is inconsistent. In this analysis, lower socioeconomic status was found to be associated with both stage at diagnosis and cancer‐specific mortality of major cancer types in a Canadian province.
A protective relationship has been hypothesized between exposure to solar ultraviolet radiation (UVR) and the development of breast cancer.
The objective of this study was to conduct a systematic ...literature review and meta-analysis of studies examining the association of exposure to solar UVR and breast cancer risk.
We searched Medline, EMBASE, and Web of Science for all studies investigating exposure to solar UVR and breast cancer risk. Separate analyses were performed using estimates of time spent in the sun, and ambient UVR. Associations were estimated using DerSimonian and Laird random-effect models. Heterogeneity was investigated through subgroup analyses and
statistics.
Fourteen studies were included in the review and 13 in the meta-analysis, with the majority (
) conducted in North America. We observed a decreased risk of breast cancer for individuals spending
in the sun during summer months over a lifetime or usual adulthood compared with
; 95% CI: 0.77, 0.91. Spending
in the sun had a similar protective effect as 1 to
when compared with
(
0.83; 95% CI: 0.75, 0.93 vs. 0.83; 95% CI: 0.78, 0.89). Exposure during adolescence was suggestive of a lower risk of breast cancer than exposure later in life (
of age) (
0.83; 95% CI: 0.71, 0.98 vs. 0.97; 95% CI: 0.85, 1.11). Ambient UVR was not associated with the risk of breast cancer (
1.00; 95% CI: 0.93, 1.09).
To our knowledge, this was the first meta-analysis to estimate the risk of developing breast cancer associated with time spent in the sun. The results suggest that obtaining greater than an hour a day in the sun during the summer months could decrease the risk of developing breast cancer. https://doi.org/10.1289/EHP4861.
The incidence of early-onset (<50 years of age) colorectal cancer (eoCRC) has been steadily increasing in high-income countries including Canada. Despite this increase in incidence, the etiology of ...eoCRC remains unclear and prospective cohort studies of potential risk factors are limited.
We examined two prospective cohorts of healthy individuals (<50 years of age) who completed baseline questionnaires in the Ontario Health Study and Alberta’s Tomorrow Project. We examined the associations between demographic characteristics, chronic health conditions, and lifestyle behaviours with the development of eoCRC using Cox proportional hazard models. Cohorts were analyzed separately and hazard ratios for each risk factor were pooled with random effects meta-analyses.
During an average follow-up of 6.63 years, 98 eoCRC cases occurred among study participants (n=127,852). A family history of CRC alone or with a history of other cancer types was associated with an increased risk of developing eoCRC (HR: 2.76, 95% CI: 1.43–5.32), but a family history of a non-CRC cancer only was not (HR: 1.18, 95% CI: 0.61–2.30). Heavy smokers (≥ 10 pack-years) at baseline had a higher risk of eoCRC compared to non-smokers (HR: 1.87, 95% CI: 1.00–3.52). Sex, socioeconomic factors, diabetes, alcohol consumption, among other factors were not significantly associated with the risk of eoCRC.
Our findings indicate that specific CRC risk factors are also associated with developing eoCRC. The data in the study offers valuable insights that could be integrated in future meta-analyses. Additional prospective cohort studies are required to understand the etiology of eoCRC.
•Family history of CRC significantly increases eoCRC risk.•Heavy smoking at baseline is a notable risk factor for eoCRC.•Socioeconomic factors, diabetes, and alcohol showed no significant eoCRC risk.•Data suggests a need for further research to clarify eoCRC etiology.
The COVID-19 pandemic is suspected to have affected cancer care and outcomes among patients in Canada. In this study, we evaluated the impact of the state of emergency period during the COVID-19 ...pandemic (Mar. 17 to June 15, 2020) on cancer diagnoses, stage at diagnosis and 1-year survival in Alberta.
We included new diagnoses of the 10 most prevalent cancer types from Jan. 1, 2018, to Dec. 31, 2020. We followed patients up to Dec. 31, 2021. We used interrupted time series analysis to examine the impact of the first COVID-19-related state of emergency in Alberta on the number of cancer diagnoses. We used multivariable Cox regression to compare 1-year survival of the patients who received a diagnosis during 2020 after the state of emergency with those who received a diagnosis during 2018 and 2019. We also performed stage-specific analyses.
We observed significant reductions in diagnoses of breast cancer (incidence rate ratio IRR 0.67, 95% confidence interval CI 0.59-0.76), prostate cancer (IRR 0.64, 95% CI 0.56-0.73) and colorectal cancer (IRR 0.64, 95% CI 0.56- 0.74) and melanoma (IRR 0.57, 95% CI 0.47-0.69) during the state of emergency period compared with the period before it. These decreases largely occurred among early-stage rather than late-stage diagnoses. Patients who received a diagnosis of colorectal cancer, non-Hodgkin lymphoma and uterine cancer in 2020 had lower 1-year survival than those diagnosed in 2018; no other cancer sites had lower survival.
The results from our analyses suggest that health care disruptions during the COVID-19 pandemic in Alberta considerably affected cancer outcomes. Given that the largest impact was observed among early-stage cancers and those with organized screening programs, additional system capacity may be needed to mitigate future impact.
The association between red meat consumption and colorectal cancer has been rigorously examined. However, a more comprehensive understanding of how the intake of unprocessed red meat contributes to ...the development of early precancerous colorectal lesions, such as advanced colorectal adenomas (ACRAs), requires further investigation. We examined the associations between different types of red meat intake and ACRAs in a sample population of 1083 individuals aged ≥ 50 years undergoing an initial screening colonoscopy in Calgary, Alberta, Canada. Associations between grams per day of total, processed, and unprocessed red meat from diet history questionnaires and ACRAs were evaluated with multivariable logistic regression models. We also applied cubic spline models fitted with three knots (10th, 50th, and 90th percentiles) to identify potential nonlinear associations. We did not observe a meaningful association between unprocessed red meat intake and the presence of ACRAs. In contrast, for every 10 g/d increase in total and processed meat intake, we observed an increase in the odds of ACRAs at the screening colonoscopy (adjusted odds ratio (OR) = 1.05, 95% CI = 1.01-1.09,
= 0.04) and (adjusted OR = 1.11, 95% CI = 1.02-1.20,
= 0.02), respectively. This study highlights the importance of differentiating between types of red meat consumption in the context of dietary risks associated with ACRAs.
Early-onset breast cancer (EoBC), defined by a diagnosis <40 years of age, is associated with poor prognosis. This study investigated the mutational landscape of non-metastatic EoBC and the ...prognostic relevance of mutational signatures using 100 tumour samples from Alberta, Canada. The MutationalPatterns package in R/Bioconductor was used to extract de novo single-base substitution (SBS) and insertion-deletion (indel) mutational signatures and to fit COSMIC SBS and indel signatures. We assessed associations between these signatures and clinical characteristics of disease, in addition to recurrence-free (RFS) and overall survival (OS). Five SBS and two indel signatures were extracted. The SBS13-like signature had higher relative contributions in the HER2-enriched subtype. Patients with higher than median contribution tended to have better RFS after adjustment for other prognostic factors (HR = 0.29; 95% CI: 0.08-1.06). An unsupervised clustering algorithm based on absolute contribution revealed three clusters of fitted COSMIC SBS signatures, but cluster membership was not associated with clinical variables or survival outcomes. The results of this exploratory study reveal various SBS and indel signatures may be associated with clinical features of disease and prognosis. Future studies with larger samples are required to better understand the mechanistic underpinnings of disease progression and treatment response in EoBC.
Background
This study aimed to describe treatment patterns and overall survival (OS) in patients with advanced non–small cell lung cancer (aNSCLC) in three countries between 2011 and 2020.
Methods
...Three databases (US, Canada, Germany) were used to identify incident aNSCLC patients. OS was assessed from the date of incident aNSCLC diagnosis and, for patients who received at least a first line of therapy (1LOT), from the date of 1LOT initiation. In multivariable analyses, we analyzed the influence of index year and type of prescribed treatment on OS.
Findings
We included 51,318 patients with an incident aNSCLC diagnosis. The percentage of patients treated with a 1LOT differed substantially between countries, whereas the number of patients receiving immunotherapies/targeted treatments increased over time in all three countries. Median OS from the date of incident diagnosis was 9.9 months in the United States vs. 4.1 months in Canada. When measured from the start of 1LOT, patients had a median OS of 10.7 months in the United States, 10.9 months in Canada, and 10.9 months in Germany. OS from the start of 1LOT improved in all three countries from 2011 to 2020 by approximately 3 to 4 months.
Conclusions
Observed continuous improvement in OS among patients receiving at least a 1LOT from 2011 to 2020 was likely driven by improved care and changes in the treatment landscape. The difference in the proportion of patients receiving a 1LOT in the observed countries requires further investigation.
Observed continuous improvement in overall survival among patients receiving at least a first line of therapy from 2011 to 2020 was likely driven by improved care and changes in treatment landscape. The difference in the proportion of patients receiving a first line of therapy in the observed countries requires further investigation.
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