Cancer Council Victoria

Wong C., Mohamad Asfia S.K., Myles P.S., Cunningham J., Greenhalgh E.M., Dean E., Doncovio S., Briggs L., Graves N., McCaffrey N.

ImportanceSurgical cancer treatments may be delayed for patients who smoke over concerns for increased risk of complications. Quantifying risks for people who had recently smoked can inform any trade-offs of delaying surgery.ObjectiveTo investigate the association between smoking status or smoking cessation time and complications after cancer surgery.Data SourcesEmbase, CINAHL, Medline COMPLETE, and Cochrane Library were systematically searched for studies published from January 1, 2000, to August 10, 2023.Study SelectionObservational and interventional studies comparing the incidence of complications in patients undergoing cancer surgery who do and do not smoke.Data Extraction and SynthesisTwo reviewers screened results and extracted data according to the Meta-Analyses of Observational Studies in Epidemiology (MOOSE) reporting guidelines. Data were pooled with a random-effects model and adjusted analysis was performed.Main Outcomes and MeasuresThe odds ratio (OR) of postoperative complications (of any type) for people who smoke currently vs in the past (4-week preoperative cutoff), currently smoked vs never smoked, and smoked within shorter (2-week cutoff) and longer (1-year cutoff) time frames.ResultsThe meta-analyses across 24 studies with a pooled sample of 39 499 participants indicated that smoking within 4 weeks preoperatively was associated with higher odds of postoperative complications compared with ceasing smoking for at least 4 weeks (OR, 1.31 [95% CI, 1.10-1.55]; n = 14 547 [17 studies]) and having never smoked (OR, 2.83 [95% CI, 2.06-3.88]; n = 9726 [14 studies]). Within the shorter term, there was no statistically significant difference in postoperative complications between people who had smoked within 2 weeks preoperatively and those who had stopped between 2 weeks and 3 months in postoperative complications (OR, 1.19 [95% CI, 0.89-1.59]; n = 5341 [10 studies]), although the odds of complications among people who smoked within a year of surgery were higher compared with those who had quit smoking for at least 1 year (OR, 1.13 [95% CI, 1.00-1.29]; N = 31 238 [13 studies]). The results from adjusted analyses were consistent with the key findings.Conclusions and RelevanceIn this systematic review and meta-analysis of smoking cessation and complications after cancer surgery, people with cancer who had stopped smoking for at least 4 weeks before surgery had fewer postoperative complications than those smoking closer to surgery. High quality, intervention-based evidence is needed to identify the optimal cessation period and inform clinicians on the trade-offs of delaying cancer surgery.

Albers F.E., Dashti S.G., Lynch B.M.

Abstract In this issue of Cancer Epidemiology, Biomarkers & Prevention, Brantley and colleagues investigated the relationships between estrogen metabolites and postmenopausal breast cancer, using data from a nested case–control study within the Nurses’ Health Study. One study aim was to investigate the extent to which estrogen metabolism patterns provided further insights into mechanisms in breast cancer development beyond the role of estradiol. In this editorial, we describe the challenges in interpreting results from observational studies of biomarkers and their role in carcinogenesis due to: (i) a general lack of clarity in the research question, (ii) the limits of current knowledge about the complex underlying causal structure involving interrelated biomarkers, and (iii) the limitations in existing data sources (e.g., biomarkers measured at a single time point). We propose that applying a formal causal inference framework in these studies could be a step forward in improving their rigor, by enabling researchers to be more explicit about the causal effects of interest and the assumptions made, and to advocate for the improvement of future studies. See related article by Brantley et al., p. 375

Chalitsios C.V., Markozannes G., Papagiannopoulos C., Aglago E.K., Berndt S.I., Buchanan D.D., Campbell P.T., Cao Y., Chan A.T., Dimou N., Drew D.A., French A.J., Georgeson P., Giannakis M., Gruber S.B., et. al.

Abstract Background: Waist circumference (WC) and its allometric counterpart, “a body shape index” (ABSI), are risk factors for colorectal cancer; however, it is uncertain whether associations with these body measurements are limited to specific molecular subtypes of the disease. Methods: Data from 2,772 colorectal cancer cases and 3,521 controls were pooled from four cohort studies within the Genetics and Epidemiology of Colorectal Cancer Consortium. Four molecular markers (BRAF mutation, KRAS mutation, CpG island methylator phenotype, and microsatellite instability) were analyzed individually and in combination (Jass types). Multivariable logistic and multinomial logistic models were used to assess the associations of WC and ABSI with overall colorectal cancer risk and, in case-only analyses, to evaluate heterogeneity by molecular subtype, respectively. Results: Higher WC (ORper 5 cm = 1.06, 95% confidence interval, 1.04–1.09) and ABSI (ORper 1-SD = 1.07, 95% confidence interval, 1.00–1.14) were associated with elevated colorectal cancer risk. There was no evidence of heterogeneity between the molecular subtypes. No difference was observed regarding the influence of WC and ABSI on the four major molecular markers in proximal colon, distal colon, and rectal cancers, as well as in early- and late-onset colorectal cancers. Associations did not differ in the Jass-type analysis. Conclusions: Higher WC and ABSI were associated with elevated colorectal cancer risk; however, they do not differentially influence all four major molecular mutations involved in colorectal carcinogenesis but underscore the importance of maintaining a healthy body weight in colorectal cancer prevention. Impact: The proposed results have potential utility in colorectal cancer prevention.

Papadimitriou N., Kazmi N., Tsilidis K.K., Richmond R.C., Lynch B.M., Bendinelli B., Ricceri F., Sánchez M., Trobajo-Sanmartín C., Jakszyn P., Simeon V., Severi G., Perduca V., Truong T., Ferrari P., et. al.

Abstract Background: Current evidence suggests higher physical activity (PA) levels are associated with a reduced risk of colorectal cancer. However, the mediating role of the circulating metabolome in this relationship remains unclear. Methods: Targeted metabolomics data from 6,055 participants in the European Prospective Investigation into Cancer and Nutrition cohort were used to identify metabolites associated with PA and derive a metabolomic signature of PA levels. PA levels were estimated using the validated Cambridge PA index based on baseline questionnaires. Mediation analyses were conducted in a nested case–control study (1,585 cases, 1,585 controls) to examine whether individual metabolites and the metabolomic signature mediated the PA–colorectal cancer association. Results: PA was inversely associated with colorectal cancer risk (OR per category change: 0.90, 95% confidence interval, 0.83–0.97; P value = 0.009). PA levels were associated with 24 circulating metabolites after FDR correction, with the strongest associations observed for phosphatidylcholine acyl-alkyl (PC ae) C34:3 (FDR-adjusted P value = 1.18 × 10−10) and lysophosphatidylcholine acyl C18:2 (FDR-adjusted P value = 1.35 × 10−6). PC ae C34:3 partially mediated the PA–colorectal cancer association (natural indirect effect: 0.991, 95% confidence interval, 0.982–0.999; P value = 0.04), explaining 7.4% of the association. No mediation effects were observed for the remaining metabolites or the overall PA metabolite signature. Conclusions: PC ae C34:3 mediates part of the PA–colorectal cancer inverse association, but further studies with improved PA measures and extended metabolomic panels are needed. Impact: These findings provide insights into PA-related biological mechanisms influencing colorectal cancer risk and suggest potential targets for cancer prevention interventions.

Lynch B.M., Bassett J.K., Milne R.L., Patel A.V., Rees‐Punia E., Lee I., Moore S.C., Matthews C.E.

AbstractBackgroundPrevious estimates of the number of cancers attributable to physical inactivity in the United States have typically focused on only three malignancies (colon, endometrial, and postmenopausal breast cancer). Contemporary epidemiologic evidence suggests that physical inactivity could contribute to up to 15 types of cancer, and a dose–response effect has been demonstrated for 13 of these. This study estimated the number of cancers diagnosed in the United States in 2015 due to physical inactivity for these 13 sites.MethodsData from the 2005 National Health Interview Survey were used to estimate physical activity prevalence and, with the assumption of a 10‐year latency period, 2015 cancer incidence data from the National Program of Cancer Registries and Surveillance, Epidemiology, and End Results Incidence US Cancer Statistics Public Use Database.ResultsThe potential impact fraction was estimated to be 4.1%, which meant that 30,951 of 761,625 incident cancers at the 13 sites could have been prevented in the United States in 2015 if adults had increased physical activity by one category in 2005 (approximately 7.5 additional metabolic equivalent task hours per week [MET‐h/week]). Theoretically, 85,415 of 761,625 incident cancers at the 13 sites (population attributable fraction, 11.2%) could have been prevented if all adults had achieved the highest level of physical activity (>30 MET‐h/week).ConclusionsWhen estimates are based on updated epidemiologic evidence regarding physical inactivity and cancer risk, substantially more cancers are attributable to physical inactivity than previously reported. A greater focus on physical activity promotion is warranted for cancer control in the United States.

Taye Merga B., McCaffrey N., Robinson S., Turi E., Lal A.

Although substantial evidence exists on the costs and benefits of cancer care and screening programs for the general population, economic evidence of interventions addressing inequalities is less well known. This systematic review summarised economic evaluations of interventions addressing inequalities in cancer screening and care to inform decision-makers on the value for money of such interventions.

Phillips K., Kotsopoulos J., Domchek S.M., Terry M.B., Chamberlain J.A., Bassett J.K., Aeilts A.M., Andrulis I.L., Buys S.S., Cui W., Daly M.B., Eisen A.F., Foulkes W.D., Friedlander M.L., Gronwald J., et. al.

PURPOSE It is uncertain whether, and to what extent, hormonal contraceptives increase breast cancer (BC) risk for germline BRCA1 or BRCA2 mutation carriers. METHODS Using pooled observational data from four prospective cohort studies, associations between hormonal contraceptive use and BC risk for unaffected female BRCA1 and BRCA2 mutation carriers were assessed using Cox regression. RESULTS Of 3,882 BRCA1 and 1,509 BRCA2 mutation carriers, 53% and 71%, respectively, had ever used hormonal contraceptives for at least 1 year (median cumulative duration of use, 4.8 and 5.7 years, respectively). Overall, 488 BRCA1 and 191 BRCA2 mutation carriers developed BC during median follow-up of 5.9 and 5.6 years, respectively. Although for BRCA1 mutation carriers, neither current nor past use of hormonal contraceptives for at least 1 year was statistically significantly associated with BC risk (hazard ratio [HR], 1.40 [95% CI, 0.94 to 2.08], P = .10 for current use; 1.16 [0.80 to 1.69], P = .4, 1.40 [0.99 to 1.97], P = .05, and 1.27 [0.98 to 1.63], P = .07 for past use 1-5, 6-10, and >10 years before, respectively), ever use was associated with increased risk (HR, 1.29 [95% CI, 1.04 to 1.60], P = .02). Furthermore, BC risk increased with longer cumulative duration of use, with an estimated proportional increase in risk of 3% (1%-5%, P = .002) for each additional year of use. For BRCA2 mutation carriers, there was no evidence that current or ever use was associated with increased BC risk (HR, 0.70 [95% CI, 0.33 to 1.47], P = .3 and 1.07 [0.73 to 1.57], P = .7, respectively). CONCLUSION Hormonal contraceptives were associated with increased BC risk for BRCA1 mutation carriers, especially if used for longer durations. Decisions about their use in women with BRCA1 mutations should carefully weigh the risks and benefits for each individual.

Marquina C., Lloyd M., Ng W., Hess J., Evans S., Ademi Z.

Albers F.E., Moreno-Betancur M., Milne R.L., English D.R., Lynch B.M., Dashti S.G.

Grant R., Mooney-Somers J., McNair R., Pennay A., Segan C., Power J., Bourne A.

BackgroundSmoking rates have declined markedly in Australia over time; however, lesbian, bisexual and queer (LBQ) women continue to smoke at higher rates than heterosexual women. Understanding the factors influencing smoking in this population is crucial for developing targeted cessation interventions and other supports.MethodsExperiences of and motivations for smoking among 42 LBQ cisgender and transgender women and non-binary people in Australia who currently or previously smoked were explored through semi-structured interviews. Participants were primarily white Australian cisgender women in their 30s–40s. Thematic analysis was used to identify common psychological, social and cultural influences on smoking.ResultsWhile coping with minority stress was a common factor influencing some participants’ smoking behaviours, participants also described how smoking offered pleasurable opportunities for gender expression, affirmation and rebellion. Smoking also enabled participants to experience ‘marginalised connectivity’, a form of social solidarity fostered through the sharing of a stigmatised practice by an oppressed or stigmatised community.ConclusionThis article identifies factors contributing to the ongoing socio-cultural relevance of smoking for some LBQ women in Australia. These specific psychological, social and cultural contexts remain salient for LBQ women’s smoking and must be factored into smoking cessation campaigns and programme designs for this population. Tailored messaging that emphasises alternative self-care strategies and the benefits of quitting in the context of supportive communities may be more effective in engaging LBQ women than long-term health risk messages.

Gama M.A., Tonmukayakul U., Saraswat N., McCaffrey N., Nguyen T.M.

ABSTRACTObjectivesThe aim of this study is to estimate the economic burden of oral cancer in Australia from the societal perspective.MethodsThe population consisted of the prevalence of lip and oral cavity cancer, and other lip, oral cavity, and pharynx cancers for ages 40 years and older. Healthcare costs of oral cancer were estimated using 2019–2020 Australian Disease Expenditure Data. Productivity losses were estimated using disability‐adjusted life years, derived from the 2019 Global Burden of Disease Study and 2019 Australian gross domestic product per capita.ResultsThe estimated annual healthcare costs for oral cancer in Australia were approximately AUD$113.2 million. Over half of the total healthcare costs (54%) were attributable to public hospital admissions (AUD$61.2 million), followed by private hospital services (28%) and pharmaceutical benefits (8%). The total costs, including healthcare and productivity losses, were around AUD$2.1 billion. The productivity losses due to oral cancer were higher for males compared to females (AUD$1.5 billion versus AUD$0.6 billion).ConclusionsThe study reveals a significant economic burden of oral cancer for 2019 in Australia at AUD$2.1 billion, largely due to productivity losses and public hospital admissions. This highlights the need for effective screening and prevention programs.

Shemesh B., Opie J.L., Dunn R.L., Mclaughlin G., Argawal V., Pomery A., Manus C.M., O'Brien C., Lewis K., Shub M., Wilton P., Satasivam P., Evans M., Millar J., Evans S.M.

ABSTRACTIntroductionMen with prostate cancer (PCa) and their support providers face challenges in accessing high‐quality, impartial information tailored to their specific needs to enhance their overall care and decision‐making. We describe the development, piloting and evaluation of the co‐designed web portal ‘BroSupPORT’.MethodsIT teams developed and integrated BroSupPORT into the Victorian Prostate Cancer Outcomes Registry (PCOR‐Vic) electronic patient‐reported outcome follow‐up process. A comparator tool was built enabling men to compare their patient‐reported outcome results against men of similar age, risk profile and after the same treatment. PCOR‐Vic participants were invited to access BroSupPORT after 12 months of follow‐up patient‐reported outcome measure completion. Factors associated with consent to BroSupPORT were determined using logistic regression. Portal access data were gathered from PCOR‐Vic data extracts and Google Analytics. A survey on portal exit and 2 weeks after consent was used to collect feedback.ResultsOver a 4‐month pilot, 331/583 (57%) men consented to accessing BroSupPORT. Among those men who accessed the portal, the majority (209/331 =63%) were diagnosed in a private hospital and resided in a major city (214/331=65%). On average, men spent 3:20 min on the portal, with sexual function aspects receiving the most attention. Twenty‐three percent of men revisited the portal during the pilot. Most men found the portal easy to use, reassuring and informative, while 9% found the patient‐reported comparisons difficult to interpret.ConclusionA patient portal—enabling men to compare their patient‐reported outcomes with other similar men and providing access to information and resources—may be a scalable solution in addressing the complex supportive care needs of men with PCa on a population basis.

Albers F.E., Swain C.T., Lou M.W., Dashti S.G., Rinaldi S., Viallon V., Karahalios A., Brown K.A., Gunter M.J., Milne R.L., English D.R., Lynch B.M.

Abstract Background: Higher concentration of insulin-like growth factor-1 (IGF-1) increases postmenopausal breast cancer risk, but evidence for insulin and c-peptide is limited. Furthermore, not all studies have accounted for potential confounding by biomarkers from other biological pathways, and not all were restricted to estrogen receptor (ER)–positive breast cancer. Methods: This was a case–cohort study of 1,223 postmenopausal women (347 with ER-positive breast cancer) from the Melbourne Collaborative Cohort Study. We measured insulin, c-peptide, IGF-1, insulin-like growth factor binding protein-3, and biomarkers of inflammatory and sex-steroid hormone pathways. Poisson regression with a robust variance estimator was used to estimate risk ratios (RR) and 95% confidence intervals (95% CI) for ER-positive breast cancer per doubling plasma concentration and for quartiles, without and with adjustment for other, potentially confounding biomarkers. Results: ER-positive breast cancer risk was not associated with doubling of insulin (RR = 0.97, 95% CI, 0.82–1.14) or c-peptide (RR = 1.01, 95% CI, 0.80–1.26). Risk seemed to decrease with doubling IGF-1 (RR = 0.80, 95% CI, 0.62–1.03) and insulin-like growth factor binding protein-3 (RR = 0.62, 95% CI, 0.41–0.90). RRs were not meaningfully different when exposures were modeled as quartiles. RRs were less than unity but imprecise after adjustment for inflammatory and sex-steroid hormone biomarkers. Conclusions: Circulating insulin, c-peptide, and IGF-1 were not positively associated with risk of ER-positive breast cancer in this case–cohort analysis of postmenopausal women. Impact: Associations between insulin and c-peptide and risk of ER-positive breast cancer in postmenopausal women are likely to be weak.

Bechelli M.L., Ivanova K., Tan S.S., Kumar B., Swiatek D., Arulananda S., Evans S.M.

PURPOSE Enhancing the speed and efficiency of clinical trial recruitment is a key objective across international health systems. This study aimed to use artificial intelligence (AI) applied in the Victorian Cancer Registry (VCR), a population-based cancer registry, to assess (1) if VCR received all relevant pathology reports for three clinical trials, (2) AI accuracy in auto-extracting information from pathology reports for recruitment, and (3) the number of participants approached for trial enrollment using the AI approach compared with standard hospital-based recruitment. METHODS To verify pathology report accessibility for VCR trial enrollment, reports from the laboratory were cross-referenced. To determine the accuracy of a Rapid Case Ascertainment (RCA) module of the AI software in extracting key clinical variables from the pathology report, data were compared with manually reviewed reports. To examine the effectiveness of the AI recruitment approach, the number of patients approached for recruitment was compared with standard practice. RESULTS Of the 195 reports provided by the pathology laboratory, 185 (94.9%) were received by VCR, 73 of 195 (37.4%) were eligible for the studies, and 5 of 73 (6.8%) eligible cases had not been received by the VCR. The RCA module demonstrated an accuracy of 93% and an F1 score of 0.94 in extracting key clinical variables. However, the RCA false-positive rate was 10% and the false-negative rate was 5%. The standard hospital approach selected fewer cases for approach to clinical trials compared with the RCA module approach, 8 of 336 (2.4%) versus 12 of 336 (3.6%), respectively. CONCLUSION Using AI to screen potentially eligible cases for recruitment to three clinical trials resulted in a 50% increase in eligible cases being approached for enrollment.

Greenhalgh E.M., Scully M., Scollo M., Durkin S.J.

Substantial increases in vaping among young people in recent years is of great concern, and governments around the world have implemented a range of policies and programmes to discourage uptake of e-cigarettes.1 Effective monitoring and evaluations are needed to inform regulations that aim to prevent youth vaping, including examining prevalence of e-cigarette use within the different regulatory environments. However, a rapidly evolving product landscape, differences in the wording and timing of questions between surveys, and difficulties in accurately capturing frequency of use can lead to challenges in accurately quantifying and comparing youth vaping.2 3 When analysing youth vaping across countries it is crucial that the data selected are as comparable as possible—in respondents, age groups and survey methods. Major international surveys such as the Global Youth Tobacco Survey have a globally standardised methodology and provide a reliable means of comparing smoking and vaping among young people in many countries.4 However, no such survey includes countries such as Australia, Canada, the USA and the UK where youth vaping has been subject to intense scrutiny and debate and across which there have been substantial variations in vaping related policies and regulations introduced over time. Several commentators have claimed that vaping among young people in Australia is similar or higher than in countries with fewer e-cigarette restrictions,5–7 and some argue that strong regulation of e-cigarettes may in fact increase youth …