Outcomes from low-risk ductal carcinoma in situ: a systematic review and meta-analysis.

PURPOSE: The current standard of treatment for ductal carcinoma in situ (DCIS) is surgery with or without adjuvant radiotherapy. With a growing debate about overdiagnosis and overtreatment of low-risk DCIS, active surveillance is being explored in several ongoing trials. We conducted a systematic review and meta-analysis to evaluate the recurrence of low-risk DCIS under various treatment approaches. METHODS: PubMed, Embase, Web of Science, and Cochrane were searched for studies reporting ipsilateral breast tumour event (IBTE), contralateral breast cancer (CBC), and breast cancer-specific survival (BCSS) rates at 5 and 10 years in low-risk DCIS. The primary outcome was invasive IBTE (iIBTE) defined as invasive progression in the ipsilateral breast. RESULTS: Thirty three eligible studies were identified, involving 47,696 women with low-risk DCIS. The pooled 5-year and 10-year iIBTE rates were 3.3% (95% confidence interval [CI]: 1.3, 8.1) and 5.9% (95% CI: 3.8, 9.0), respectively. The iIBTE rates were significantly lower in patients who underwent surgery compared to those who did not, at 5 years (3.5% vs. 9.0%, P = 0.003) and 10 years (6.4% vs. 22.7%, P = 0.008). Similarly, the 10-year BCSS rate was higher in the surgery group (96.0% vs. 99.6%, P = 0.010). In patients treated with breast-conserving surgery, additional radiotherapy significantly reduced IBTE risk, but not total-CBC risk. CONCLUSION: This review showed a lower risk of progression and better survival in women who received surgery and additional RT for low-risk DCIS. However, our findings were primarily based on observational studies, and should be confirmed with the results from the ongoing trials.

Ethnic differences in the characteristics of patients with newly diagnosed lung cancer in the Te Manawa Taki region of New Zealand.

BACKGROUND: Maori have three times the mortality from lung cancer compared with non-Maori. The Te Manawa Taki region has a population of 900 000, of whom 30% are Maori. We have little understanding of the factors associated with developing and diagnosing lung cancer and ethnic differences in these characteristics. AIMS: To explore the differences in the incidence and characteristics of patients with newly diagnosed lung cancer between Maori and non-Maori. METHODS: Patients were identified from the regional register. Incidence rates were calculated based on population data from the 2013 and 2018 censuses. The patient and tumour characteristics of Maori and non-Maori were compared. The analysis used Χ2 tests and logistic models for categorical variables and Student t tests for continuous variables. RESULTS: A total of 4933 patients were included, with 1575 Maori and 3358 non-Maori. The age-standardised incidence of Maori (236 per 100 000) was 3.3 times higher than that of non-Maori. Maori were 1.3 times more likely to have an advanced stage of disease and 1.97 times more likely to have small cell lung cancer. Maori were more likely to have comorbidities, chronic obstructive pulmonary disease, cardiovascular disease and diabetes. They also had higher levels of social deprivation and tended to be younger, female and current smokers. CONCLUSIONS: The findings point to the need to address barriers to early diagnosis and the need for system change including the need to introduce a lung cancer screening focussing on Maori. There is also the need for preventive programmes to address comorbidities that impact lung cancer outcomes as well as a continued emphasis on creating a smoke-free New Zealand.

Shifting incidence and survival of epithelial ovarian cancer (1995-2014): A SurvMark-2 study.

The aim of the study is to provide a comprehensive assessment of incidence and survival trends of epithelial ovarian cancer (EOC) by histological subtype across seven high income countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the United Kingdom). Data on invasive EOC diagnosed in women aged 15 to 99 years during 1995 to 2014 were obtained from 20 cancer registries. Age standardized incidence rates and average annual percentage change were calculated by subtype for all ages and age groups (15-64 and 65-99 years). Net survival (NS) was estimated by subtype, age group and 5-year period using Pohar-Perme estimator. Our findings showed marked increase in serous carcinoma incidence was observed between 1995 and 2014 among women aged 65 to 99 years with average annual increase ranging between 2.2% and 5.8%. We documented a marked decrease in the incidence of adenocarcinoma "not otherwise specified" with estimates ranging between 4.4% and 7.4% in women aged 15 to 64 years and between 2.0% and 3.7% among the older age group. Improved survival, combining all EOC subtypes, was observed for all ages combined over the 20-year study period in all countries with 5-year NS absolute percent change ranging between 5.0 in Canada and 12.6 in Denmark. Several factors such as changes in guidelines and advancement in diagnostic tools may potentially influence the observed shift in histological subtypes and temporal trends. Progress in clinical management and treatment over the past decades potentially plays a role in the observed improvements in EOC survival.

International variation in oesophageal and gastric cancer survival 2012-2014: differences by histological subtype and stage at diagnosis (an ICBP SURVMARK-2 population-based study).

OBJECTIVE: To provide the first international comparison of oesophageal and gastric cancer survival by stage at diagnosis and histological subtype across high-income countries with similar access to healthcare. METHODS: As part of the ICBP SURVMARK-2 project, data from 28 923 patients with oesophageal cancer and 25 946 patients with gastric cancer diagnosed during 2012-2014 from 14 cancer registries in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK) were included. 1-year and 3-year age-standardised net survival were estimated by stage at diagnosis, histological subtype (oesophageal adenocarcinoma (OAC) and oesophageal squamous cell carcinoma (OSCC)) and country. RESULTS: Oesophageal cancer survival was highest in Ireland and lowest in Canada at 1 (50.3% vs 41.3%, respectively) and 3 years (27.0% vs 19.2%) postdiagnosis. Survival from gastric cancer was highest in Australia and lowest in the UK, for both 1-year (55.2% vs 44.8%, respectively) and 3-year survival (33.7% vs 22.3%). Most patients with oesophageal and gastric cancer had regional or distant disease, with proportions ranging between 56% and 90% across countries. Stage-specific analyses showed that variation between countries was greatest for localised disease, where survival ranged between 66.6% in Australia and 83.2% in the UK for oesophageal cancer and between 75.5% in Australia and 94.3% in New Zealand for gastric cancer at 1-year postdiagnosis. While survival for OAC was generally higher than that for OSCC, disparities across countries were similar for both histological subtypes. CONCLUSION: Survival from oesophageal and gastric cancer varies across high-income countries including within stage groups, particularly for localised disease. Disparities can partly be explained by earlier diagnosis resulting in more favourable stage distributions, and distributions of histological subtypes of oesophageal cancer across countries. Yet, differences in treatment, and also in cancer registration practice and the use of different staging methods and systems, across countries may have impacted the comparisons. While primary prevention remains key, advancements in early detection research are promising and will likely allow for additional risk stratification and survival improvements in the future.

Pancreatic cancer survival by stage and age in seven high-income countries (ICBP SURVMARK-2): a population-based study.

BACKGROUND: The global burden of pancreatic cancer has steadily increased, while the prognosis after pancreatic cancer diagnosis remains poor. This study aims to compare the stage- and age-specific pancreatic cancer net survival (NS) for seven high-income countries: Australia, Canada, Denmark, Ireland, New Zealand, Norway, and United Kingdom. METHODS: The study included over 35,000 pancreatic cancer cases diagnosed during 2012-2014, followed through 31 December 2015. The stage- and age-specific NS were calculated using the Pohar-Perme estimator. RESULTS: Pancreatic cancer survival estimates were low across all 7 countries, with 1-year NS ranging from 21.1% in New Zealand to 30.9% in Australia, and 3-year NS from 6.6% in the UK to 10.9% in Australia. Most pancreatic cancers were diagnosed with distant stage, ranging from 53.9% in Ireland to 83.3% in New Zealand. While survival differences were evident between countries across all stage categories at one year after diagnosis, this survival advantage diminished, particularly in cases with distant stage. CONCLUSION: This study demonstrated the importance of stage and age at diagnosis in pancreatic cancer survival. Although progress has been made in improving pancreatic cancer prognosis, the disease is highly fatal and will remain so without major breakthroughs in the early diagnosis and management.

International differences in lung cancer survival by sex, histological type and stage at diagnosis: an ICBP SURVMARK-2 Study.

INTRODUCTION: Lung cancer has a poor prognosis that varies internationally when assessed by the two major histological subgroups (non-small cell (NSCLC) and small cell (SCLC)). METHOD: 236 114 NSCLC and 43 167 SCLC cases diagnosed during 2010-2014 in Australia, Canada, Denmark, Ireland, New Zealand, Norway and the UK were included in the analyses. One-year and 3-year age-standardised net survival (NS) was estimated by sex, histological type, stage and country. RESULTS: One-year and 3-year NS was consistently higher for Canada and Norway, and lower for the UK, New Zealand and Ireland, irrespective of stage at diagnosis. Three-year NS for NSCLC ranged from 19.7% for the UK to 27.1% for Canada for men and was consistently higher for women (25.3% in the UK; 35.0% in Canada) partly because men were diagnosed at more advanced stages. International differences in survival for NSCLC were largest for regional stage and smallest at the advanced stage. For SCLC, 3-year NS also showed a clear female advantage with the highest being for Canada (13.8% for women; 9.1% for men) and Norway (12.8% for women; 9.7% for men). CONCLUSION: Distribution of stage at diagnosis among lung cancer cases differed by sex, histological subtype and country, which may partly explain observed survival differences. Yet, survival differences were also observed within stages, suggesting that quality of treatment, healthcare system factors and prevalence of comorbid conditions may also influence survival. Other possible explanations include differences in data collection practice, as well as differences in histological verification, staging and coding across jurisdictions.

Patient-reported diagnostic intervals to colorectal cancer diagnosis in the Midland region of New Zealand: a prospective cohort study.

BACKGROUND AND OBJECTIVES: New Zealand (NZ) has high rates of colorectal cancer (CRC) but low rates of early detection. The majority of CRC is diagnosed through general practice, where lengthy diagnostic intervals are common. We investigated factors contributing to diagnostic delay in a cohort of patients newly diagnosed with CRC. METHODS: Patients were recruited from the Midland region and interviewed about their diagnostic experience using a questionnaire based on a modified Model of Pathways to Treatment framework and SYMPTOM questionnaire. Descriptive statistics were used to describe the population characteristics. Chi-square analysis and logistic regression were used to analyse factors influencing diagnostic intervals. RESULTS: Data from 176 patients were analysed, of which 65 (36.9%) experienced a general practitioner (GP) diagnostic interval of >120 days and 96 (54.5%) experienced a total diagnostic interval (TDI) > 120 days. Patients reporting rectal bleeding were less likely to experience a long TDI (odds ratio [OR] 0.34, 95% confidence interval [CI]: 0.14-0.78) and appraisal/help-seeking interval (OR, 0.19, 95% CI: 0.06-0.59). Patients <60 were more likely to report a longer appraisal/help-seeking interval (OR, 3.32, 95% CI: 1.17-9.46). Female (OR, 2.19, 95% CI: 1.08-4.44) and Maori patients (OR, 3.18, 95% CI: 1.04-9.78) were more likely to experience a long GP diagnostic interval. CONCLUSION: NZ patients with CRC can experience long diagnostic intervals, attributed to patient and health system factors. Young patients, Maori, females, and patients experiencing change of bowel habit may be at particular risk. We need to increase symptom awareness of CRC for patients and GPs. Concentrated efforts are needed to ensure equity for Maori in access to screening, diagnostics, and treatment.

New Zealand has high rates of colorectal cancer but low rates of early detection. We interviewed newly diagnosed patients about their diagnostic experience to identify factors influencing time to diagnosis. More than half of patients experienced a long diagnostic interval. Young patients, Maori, females, and patients experiencing changes of bowel habit may be at particular risk for long intervals. With the diagnostic difficulty of colorectal cancer (CRC), we need to increase CRC symptom awareness for patients and general practitioners.

Metastatic relapse of stage I-III breast cancer in New Zealand.

PURPOSE: This study aims to investigate the factors that influence the risk of metastatic relapse in women presenting with stage I-III breast cancer in New Zealand. METHODS: The study included women diagnosed with stage I-III breast cancer. Cumulative incidence of distant metastatic relapse was examined with the Kaplan-Meier method by cancer stage and subtype. Cox proportional hazards models were used to estimate the adjusted hazard ratio of developing recurrent metastatic breast cancer by cancer stage and biomarker subtype after adjustment for other factors. RESULTS: A total of 17,543 eligible women were identified. The 5-year cumulative incidence of metastatic recurrence was 3.7% for stage I, 13.3% for stage II and 30.9% for stage III disease. The adjusted hazard ratios (HR) of stage II and stage III breast cancer developing metastatic disease were 2.07 and 4.82 compared to stage I. The adjusted risk of distant metastatic relapse was highest for luminal B HER2- cancers (adjusted HR: 1.59 compared to luminal A disease). Higher grade cancers were associated with a higher risk of metastases. After adjustment, women aged 60-69 years and Asian women had the lowest risk of distant metastatic relapse. CONCLUSIONS: The prognosis of women with locally invasive breast cancer differs greatly with the chance of developing metastatic disease depending on the stage of disease at diagnosis and the subtype. Grade of disease at diagnosis was also important. Maori or Pacific ethnicity did not influence the risk of developing metastatic disease, although Asian women seemed less likely to develop metastases.

Outcomes from colonoscopy following referral from New Zealand general practice: a retrospective analysis.

BACKGROUND: New Zealand has high rates of colorectal cancer (CRC) but poor outcomes. Most patients with CRC are diagnosed following referral from general practice, where a general practitioner (GP) assesses symptoms according to national guidelines. All referred patients are then re-prioritised by the hospital system. The first objective of this study was to identify what proportion of patients referred by general practice to surgical/gastroenterology at Waikato District Health Board (DHB) had a colonoscopy. The second objective was to determine what proportion of these referrals have an underlying CRC and the factors associated with the likelihood of this diagnosis. METHODS: This study is a retrospective analysis of e-referral data for patients aged 30-70+ who were referred from 75 general practices to general surgery, gastroenterology or direct to colonoscopy at Waikato DHB, 01 January 2015-31 December 2017. Primary and secondary outcome measures included the proportion and characteristics of patients who were having colonoscopy, and of those, who were diagnosed with CRC. Data were analysed using chi square and logistic regression. RESULTS: 6718/20648 (32.5%) patients had a colonoscopy and 372 (5.5%) of these were diagnosed with CRC. The probability of having CRC following a colonoscopy increased with age (p value < 0.001). Females (p value < 0.001), non-Maori (p value < 0.001), and patients with a high suspicion of cancer (HSCan) label originating from their GP were more likely to have a colonoscopy, while the odds ratio of Maori having a colonoscopy was 0.66 (95% CI 0.60-0.73). The odds ratio of a CRC diagnosis following colonoscopy was 1.67 (95% CI 1.35-2.07) for men compared to women, and 2.34 (95% CI 1.70-3.22) for those with a GP HSCan label. Of the 585 patients referred with a GP HSCan, 423 (72.3%) were reprioritised by the hospital and 55 patients had their diagnosis unnecessarily delayed. CONCLUSIONS: If a GP refers a patient with an HSCan, and the patient receives a colonoscopy, then the likelihood of having CRC is almost 15.0%. This would suggest that these patients should be routinely prioritised without further triage by the hospital. Further research is needed to understand why Maori are less likely to receive a colonoscopy following referral from general practice.

Screening for anaplastic lymphoma kinase (ALK) gene rearrangements in non-small-cell lung cancer in New Zealand.

BACKGROUND: Lung cancer is a major cause of death in New Zealand. In recent years, targeted therapies have improved outcomes. AIM: To determine the uptake of anaplastic lymphoma kinase (ALK) testing, and the prevalence, demographic profile and outcomes of ALK-positive non-small-cell lung cancer (NSCLC), in New Zealand, where no national ALK-testing guidelines or subsidised ALK tyrosine kinase inhibitor (TKI) therapies are available. METHODS: A population-based observational study reviewed databases to identify patients presenting with non-squamous NSCLC over 6.5 years in northern New Zealand. We report the proportion tested for ALK gene rearrangements and the results. NSCLC samples tested by fluorescence in situ hybridisation were retested by next generation sequencing and ALK immunohistochemistry. A survival analysis compared ALK-positive patients treated or not treated with ALK TKI therapy. RESULTS: From a total of 3130 patients diagnosed with non-squamous NSCLC, 407 (13%) were tested for ALK gene rearrangements, and patient selection was variable and inequitable. Among those tested, 34 (8.4%) had ALK-positive NSCLC. ALK-positive disease was more prevalent in younger versus older patients, non-smokers versus smokers and in Maori, Pacific or Asian ethnic groups than in New Zealand Europeans. Fluorescence in situ hybridisation, ALK immunohistochemistry and next generation sequencing showed broad concordance for detecting ALK-positive disease under local testing conditions. Among patients with ALK-positive metastatic NSCLC, those treated with ALK TKI survived markedly longer than those not treated with ALK TKI (median overall survival 5.12 vs 0.55 years). CONCLUSION: Lung cancer outcomes in New Zealand may be improved by providing national guidelines and funding policy for ALK testing and access to subsidised ALK TKI therapy.

Increasing incidence of endometrial carcinoma in a high-risk New Zealand community.

BACKGROUND: Endometrial carcinoma (EC) is increasing in incidence, attributed largely to the obesity epidemic. Ethnic differences in New Zealand have long been recognised, with Pacific women bearing the greater burden of disease. We hypothesise that the pooled national incidence rates underestimate the true burden of EC in our high-risk community. AIMS: We aimed to: (1) determine the incidence, trends and outcome of EC in the high-risk community served by our hospital, relative to national data; and (2) examine associated demographic, and clinicopathological features with reference to risk factors, to identify potential clinical and population intervention points. MATERIALS AND METHODS: All area-resident women treated for EC at Middlemore Hospital from 2000 to 2014 were identified from records, and clinicopathological data obtained. Incidence and time trend analyses were performed with reference to tumour type, age and ethnicity. RESULTS: The study included 588 women. Pacific, followed by Maori, women had the highest incidence of EC (relative risk = 5.11 and 2.47, respectively, relative to 'Other' women). The incidence increased for all ethnicities (annual percentage change (APC) of 7.3; 95% CI 3.6-11.1), most marked in women aged below 50 years (APC of 12.2; 95% CI 5.2-19.7). This occurred predominantly in Pacific women, who had a high prevalence of potentially reversible risk factors. Disease-specific survival was worse in Pacific, and to a lesser extent, Maori women. CONCLUSIONS: Prompt investigation of symptomatic, high-risk women regardless of age may detect endometrial abnormalities at an early, potentially reversible stage. The prevention and management of identifiable high-risk factors would help mitigate the risk of EC and associated diseases.

The burden of non-melanoma skin cancers in Auckland, New Zealand.

BACKGROUND/OBJECTIVES: As the New Zealand Cancer Registry does not require mandatory reporting of non-melanoma skin cancers (NMSC), basal cell carcinomas (BCC) and squamous cell carcinomas (SCC), the clinical burden of these diseases is unknown. METHODS: A retrospective review of all patients with histopathology performed allowed us to estimate invasive BCC and SCC in the Auckland region in 2008 (population 1.44 million). RESULTS: During this period, a total of 21 236 NMSC were diagnosed among 13 996 patients, consisting of 5611 SCC lesions (26%) and 15 525 (74%) BCC. The Auckland incidence rates per 100 000 were 425 for SCC and 1177 for BCC. The overall rate of NMSC per 100 000 was 1906.5 (standardised to the census data of Australia 2001); 1385 for BCC and 522 for SCC. Using published data on incidence trends and population growth, we estimate that 29 000-33 000 NMSC would have been excised in Auckland in 2016, and 78 000-87 000 in New Zealand. CONCLUSION: Auckland has the highest reported incidence of invasive NMSC in the world. We believe that high-risk cutaneous SCC and complex BCC should be recorded. Our study provides information for clinicians and health economists on the scale of the problem.

Treatment and survival disparities by ethnicity in New Zealand women with stage I-III breast cancer tumour subtypes.

PURPOSE: This study aims to look at the distribution of different subtypes of stage I-III breast cancer in Maori and Pacific versus non-Maori/Pacific women, and to examine cancer outcomes by ethnicity within these different subtypes. METHOD: This study included 9,015 women diagnosed with stage I-III breast cancer between June 2000 and May 2013, recorded in the combined Waikato and Auckland Breast Cancer Registers, who had complete data on ER, PR and HER2 status. Five ER/PR/HER2 subtypes were defined. Kaplan-Meier method and Cox proportional hazards model were used to examine ethnic disparities in breast cancer-specific survival. RESULTS: Of the 9,015 women, 891 were Maori, 548 were Pacific and 7,576 others. Both Maori and Pacific women were less likely to have triple negative breast cancer compared to others (8.6, 8.9 vs. 13.0%). Pacific women were more than twice as likely to have ER-, PR- and HER2+ cancer than Maori and others (14.2 vs. 6.0%, 6.7%). After adjustment for age, year of diagnosis, stage, grade and treatment, the hazard ratios of breast cancer-specific mortality for Maori and Pacific women with ER+, PR+ and HER2- were 1.52 (95% CI 1.06-2.18) and 1.55 (95% CI 1.04-2.31) compared to others, respectively. Maori women with HER2+ cancer were twice more likely to die of their cancer than others. CONCLUSIONS: Outcomes for Maori and Pacific women could be improved by better treatment regimens especially for those with HER2+ breast cancer and for women with ER+, PR+ and HER2- breast cancer.

Stage of breast cancer at diagnosis in New Zealand: impacts of socio-demographic factors, breast cancer screening and biology.

BACKGROUND: Examination of factors associated with late stage diagnosis of breast cancer is useful to identify areas which are amenable to intervention. This study analyses trends in cancer stage at diagnosis and impact of socio-demographic, cancer biological and screening characteristics on cancer stage in a population-based series of women with invasive breast cancer in New Zealand. METHODS: All women diagnosed with invasive breast cancer between 2000 and 2013 were identified from two regional breast cancer registries. Factors associated with advanced (stages III and IV) and metastatic (stage IV) cancer at diagnosis were analysed in univariate and multivariate models adjusting for covariates. RESULTS: Of the 12390 women included in this study 2448 (19.7%) were advanced and 575 (4.6%) were metastatic at diagnosis. Maori (OR = 1.86, 1.39-2.49) and Pacific (OR = 2.81, 2.03-3.87) compared with NZ European ethnicity, other urban (OR = 2.00, 1.37-2.92) compared with main urban residency and non-screen (OR = 6.03, 4.41-8.24) compared with screen detection were significantly associated with metastatic cancer at diagnosis in multivariate analysis. A steady increase in the rate of metastatic cancer was seen which has increased from 3.8% during 2000-2003 to 5.0% during 2010-2013 period (p = 0.042). CONCLUSIONS: Providing equitable high quality primary care and increasing mammographic screening coverage needs to be looked at as possible avenues to reduce late-stage cancer at diagnosis and to reduce ethnic, socioeconomic and geographical disparities in stage of breast cancer at diagnosis in New Zealand.

Characteristics and outcomes of lung cancer patients presenting through the emergency department: a Waikato District Health Board study.

AIM: This research examines the characteristics and survival outcomes of patients receiving a lung cancer diagnosis after attending the emergency department (ED) of Waikato hospitals in New Zealand. METHODS: This retrospective study was based on a comprehensive database of Waikato patients recorded on the Midland Lung Cancer Register from 2011 to 2021. We compared the characteristics of patients with and without emergency presentations within 14 days before their lung cancer diagnosis. The survival of patients with and without ED attendance was compared between Maori and non-Maori. This study also analysed the odds ratios (OR) of presenting via ED before diagnosis and surviving 12 months based on logistic regressions. RESULTS: In total, 2,397 patients were included, with 39.6% attending the ED prior to diagnosis. Maori were 1.27 times more likely than non-Maori to be diagnosed after attending the ED. Other characteristics of patients included being male, being diagnosed with small cell lung cancer and having more advanced-stage disease. Patients attending the ED were less likely to survive 12 months than those without ED visits (OR 0.42), and those with two or more ED visits were even less likely to survive 12 months (OR 0.33). CONCLUSION: Patients presenting through the ED have more advanced-stage disease, while those presenting through their general practitioners (GPs) have evidence of being diagnosed earlier and having better survival. Barriers to early diagnoses through attendance with a GP, particularly for Maori and for men, need to be explored.

The effect of exposure to radiofrequency fields on cancer risk in the general and working population: A systematic review of human observational studies - Part I: Most researched outcomes.

BACKGROUND: The objective of this review was to assess the quality and strength of the evidence provided by human observational studies for a causal association between exposure to radiofrequency electromagnetic fields (RF-EMF) and risk of the most investigated neoplastic diseases. METHODS: Eligibility criteria: We included cohort and case-control studies of neoplasia risks in relation to three types of exposure to RF-EMF: near-field, head-localized, exposure from wireless phone use (SR-A); far-field, whole body, environmental exposure from fixed-site transmitters (SR-B); near/far-field occupational exposures from use of hand-held transceivers or RF-emitting equipment in the workplace (SR-C). While no restrictions on tumour type were applied, in the current paper we focus on incidence-based studies of selected "critical" neoplasms of the central nervous system (brain, meninges, pituitary gland, acoustic nerve) and salivary gland tumours (SR-A); brain tumours and leukaemias (SR-B, SR-C). We focussed on investigations of specific neoplasms in relation to specific exposure sources (i.e. E-O pairs), noting that a single article may address multiple E-O pairs. INFORMATION SOURCES: Eligible studies were identified by literature searches through Medline, Embase, and EMF-Portal. Risk-of-bias (RoB) assessment: We used a tailored version of the Office of Health Assessment and Translation (OHAT) RoB tool to evaluate each study's internal validity. At the summary RoB step, studies were classified into three tiers according to their overall potential for bias (low, moderate and high). DATA SYNTHESIS: We synthesized the study results using random effects restricted maximum likelihood (REML) models (overall and subgroup meta-analyses of dichotomous and categorical exposure variables), and weighted mixed effects models (dose-response meta-analyses of lifetime exposure intensity). Evidence assessment: Confidence in evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. RESULTS: We included 63 aetiological articles, published between 1994 and 2022, with participants from 22 countries, reporting on 119 different E-O pairs. RF-EMF exposure from mobile phones (ever or regular use vs no or non-regular use) was not associated with an increased risk of glioma [meta-estimate of the relative risk (mRR) = 1.01, 95 % CI = 0.89-1.13), meningioma (mRR = 0.92, 95 % CI = 0.82-1.02), acoustic neuroma (mRR = 1.03, 95 % CI = 0.85-1.24), pituitary tumours (mRR = 0.81, 95 % CI = 0.61-1.06), salivary gland tumours (mRR = 0.91, 95 % CI = 0.78-1.06), or paediatric (children, adolescents and young adults) brain tumours (mRR = 1.06, 95 % CI = 0.74-1.51), with variable degree of across-study heterogeneity (I2 = 0 %-62 %). There was no observable increase in mRRs for the most investigated neoplasms (glioma, meningioma, and acoustic neuroma) with increasing time since start (TSS) use of mobile phones, cumulative call time (CCT), or cumulative number of calls (CNC). Cordless phone use was not significantly associated with risks of glioma [mRR = 1.04, 95 % CI = 0.74-1.46; I2 = 74 %) meningioma, (mRR = 0.91, 95 % CI = 0.70-1.18; I2 = 59 %), or acoustic neuroma (mRR = 1.16; 95 % CI = 0.83-1.61; I2 = 63 %). Exposure from fixed-site transmitters (broadcasting antennas or base stations) was not associated with childhood leukaemia or paediatric brain tumour risks, independently of the level of the modelled RF exposure. Glioma risk was not significantly increased following occupational RF exposure (ever vs never), and no differences were detected between increasing categories of modelled cumulative exposure levels. DISCUSSION: In the sensitivity analyses of glioma, meningioma, and acoustic neuroma risks in relation to mobile phone use (ever use, TSS, CCT, and CNC) the presented results were robust and not affected by changes in study aggregation. In a leave-one-out meta-analyses of glioma risk in relation to mobile phone use we identified one influential study. In subsequent meta-analyses performed after excluding this study, we observed a substantial reduction in the mRR and the heterogeneity between studies, for both the contrast Ever vs Never (regular) use (mRR = 0.96, 95 % CI = 0.87-1.07, I2 = 47 %), and in the analysis by increasing categories of TSS ("<5 years": mRR = 0.97, 95 % CI = 0.83-1.14, I2 = 41 %; "5-9 years ": mRR = 0.96, 95 % CI = 0.83-1.11, I2 = 34 %; "10+ years": mRR = 0.97, 95 % CI = 0.87-1.08, I2 = 10 %). There was limited variation across studies in RoB for the priority domains (selection/attrition, exposure and outcome information), with the number of studies evenly classified as at low and moderate risk of bias (49 % tier-1 and 51 % tier-2), and no studies classified as at high risk of bias (tier-3). The impact of the biases on the study results (amount and direction) proved difficult to predict, and the RoB tool was inherently unable to account for the effect of competing biases. However, the sensitivity meta-analyses stratified on bias-tier, showed that the heterogeneity observed in our main meta-analyses across studies of glioma and acoustic neuroma in the upper TSS stratum (I2 = 77 % and 76 %), was explained by the summary RoB-tier. In the tier-1 study subgroup, the mRRs (95 % CI; I2) in long-term (10+ years) users were 0.95 (0.85-1.05; 5.5 %) for glioma, and 1.00 (0.78-1.29; 35 %) for acoustic neuroma. The time-trend simulation studies, evaluated as complementary evidence in line with a triangulation approach for external validity, were consistent in showing that the increased risks observed in some case-control studies were incompatible with the actual incidence rates of glioma/brain cancer observed in several countries and over long periods. Three of these simulation studies consistently reported that RR estimates > 1.5 with a 10+ years induction period were definitely implausible, and could be used to set a "credibility benchmark". In the sensitivity meta-analyses of glioma risk in the upper category of TSS excluding five studies reporting implausible effect sizes, we observed strong reductions in both the mRR [mRR of 0.95 (95 % CI = 0.86-1.05)], and the degree of heterogeneity across studies (I2 = 3.6 %). CONCLUSIONS: Consistently with the published protocol, our final conclusions were formulated separately for each exposure-outcome combination, and primarily based on the line of evidence with the highest confidence, taking into account the ranking of RF sources by exposure level as inferred from dosimetric studies, and the external coherence with findings from time-trend simulation studies (limited to glioma in relation to mobile phone use). For near field RF-EMF exposure to the head from mobile phone use, there was moderate certainty evidence that it likely does not increase the risk of glioma, meningioma, acoustic neuroma, pituitary tumours, and salivary gland tumours in adults, or of paediatric brain tumours. For near field RF-EMF exposure to the head from cordless phone use, there was low certainty evidence that it may not increase the risk of glioma, meningioma or acoustic neuroma. For whole-body far-field RF-EMF exposure from fixed-site transmitters (broadcasting antennas or base stations), there was moderate certainty evidence that it likely does not increase childhood leukaemia risk and low certainty evidence that it may not increase the risk of paediatric brain tumours. There were no studies eligible for inclusion investigating RF-EMF exposure from fixed-site transmitters and critical tumours in adults. For occupational RF-EMF exposure, there was low certainty evidence that it may not increase the risk of brain cancer/glioma, but there were no included studies of leukemias (the second critical outcome in SR-C). The evidence rating regarding paediatric brain tumours in relation to environmental RF exposure from fixed-site transmitters should be interpreted with caution, due to the small number of studies. Similar interpretative cautions apply to the evidence rating of the relation between glioma/brain cancer and occupational RF exposure, due to differences in exposure sources and metrics across the few included studies. OTHER: This project was commissioned and partially funded by the World Health Organization (WHO). Co-financing was provided by the New Zealand Ministry of Health; the Istituto Superiore di Sanità in its capacity as a WHO Collaborating Centre for Radiation and Health; and ARPANSA as a WHO Collaborating Centre for Radiation Protection. REGISTRATION: PROSPERO CRD42021236798. Published protocol: [(Lagorio et al., 2021) DOI https://doi.org/10.1016/j.envint.2021.106828].

Erlotinib or Gefitinib for Treating Advanced Epidermal Growth Factor Receptor Mutation-Positive Lung Cancer in Aotearoa New Zealand: Protocol for a National Whole-of-Patient-Population Retrospective Cohort Study and Results of a Validation Substudy.

BACKGROUND: Starting in 2010, the epidermal growth factor receptor (EGFR) kinase inhibitors erlotinib and gefitinib were introduced into routine use in Aotearoa New Zealand (NZ) for treating advanced lung cancer, but their impact in this setting is unknown. OBJECTIVE: The study described in this protocol aims to understand the effectiveness and safety of these new personalized lung cancer treatments and the contributions made by concomitant medicines and other factors to adverse outcomes in the general NZ patient population. A substudy aimed to validate national electronic health databases as the data source and the methods for determining patient eligibility and identifying outcomes and variables. METHODS: This study will include all NZ patients with advanced EGFR mutation-positive lung cancer who were first dispensed erlotinib or gefitinib before October 1, 2020, and followed until death or for at least 1 year. Routinely collected health administrative and clinical data will be collated from national electronic cancer registration, hospital discharge, mortality registration, and pharmaceutical dispensing databases by deterministic data linkage using National Health Index numbers. The primary effectiveness and safety outcomes will be time to treatment discontinuation and serious adverse events, respectively. The primary variable will be high-risk concomitant medicines use with erlotinib or gefitinib. For the validation substudy (n=100), data from clinical records were compared to those from national electronic health databases and analyzed by agreement analysis for categorical data and by paired 2-tailed t tests for numerical data. RESULTS: In the validation substudy, national electronic health databases and clinical records agreed in determining patient eligibility and for identifying serious adverse events, high-risk concomitant medicines use, and other categorical data with overall agreement and κ statistic of >90% and >0.8000, respectively; for example, for the determination of patient eligibility, the comparison of proxy and standard eligibility criteria applied to national electronic health databases and clinical records, respectively, showed overall agreement and κ statistic of 96% and 0.8936, respectively. Dates for estimating time to treatment discontinuation and other numerical variables and outcomes showed small differences, mostly with nonsignificant P values and 95% CIs overlapping with zero difference; for example, for the dates of the first dispensing of erlotinib or gefitinib, national electronic health databases and clinical records differed on average by approximately 4 days with a nonsignificant P value of .33 and 95% CIs overlapping with zero difference. As of May 2024, the main study is ongoing. CONCLUSIONS: A protocol is presented for a national whole-of-patient-population retrospective cohort study designed to describe the safety and effectiveness of erlotinib and gefitinib during their first decade of routine use in NZ for treating EGFR mutation-positive lung cancer. The validation substudy demonstrated the feasibility and validity of using national electronic health databases and the methods for determining patient eligibility and identifying the study outcomes and variables proposed in the study protocol. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12615000998549; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368928. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51381.

The risk of subsequent invasive melanoma after a primary in situ or invasive melanoma in a high incidence country (New Zealand).

Background: Patients with invasive melanoma are at increased risk of developing subsequent invasive melanoma, but the risks for those with primary in situ melanoma are unclear. Objectives: To assess and compare the cumulative risk of subsequent invasive melanoma after primary invasive or in situ melanoma. To estimate the standardized incidence ratio (SIR) of subsequent invasive melanoma compared to population incidence in both cohorts. Methods: Patients with a first diagnosis of melanoma (invasive or in situ) between 2001 and 2017 were identified from the New Zealand national cancer registry, and any subsequent invasive melanoma during follow-up to the end of 2017 identified. Cumulative risk of subsequent invasive melanoma was estimated by Kaplan-Meier analysis separately for primary invasive and in situ cohorts. Risk of subsequent invasive melanoma was assessed using Cox proportional hazard models. SIR was assessed, allowing for age, sex, ethnicity, year of diagnosis and follow up time. Results: Among 33 284 primary invasive and 27 978 primary in situ melanoma patients, median follow up time was 5.5 and 5.7 years, respectively. A subsequent invasive melanoma developed in 1777 (5%) of the invasive and 1469 (5%) of the in situ cohort, with the same median interval (2.5 years) from initial to first subsequent lesion in both cohorts. The cumulative incidence of subsequent invasive melanoma at 5 years was similar in the two cohorts (invasive 4.2%, in situ 3.8%); the cumulative incidence increased linearly over time in both cohorts. The risk of subsequent invasive melanoma was marginally higher for primary invasive compared to in situ melanoma after adjustment for age, sex, ethnicity and body site of the initial lesion (hazard ratio 1.11, 95% CI 1.02-1.21). Compared to population incidence, the SIR of invasive melanoma was 4.6 (95% CI 4.3-4.9) for the primary invasive and 4 (95% CI 3.7-4.2) for the primary in situ melanoma cohorts. Conclusions: The risk of subsequent invasive melanoma is similar whether patients present with in situ or invasive melanoma. Thus follow-up surveillance for new lesions should be similar, although patients with invasive melanoma require more surveillance for recurrence.

Incidence, trends, and survival of oropharyngeal squamous cell cancer in Aotearoa New Zealand, 2006-2020.

BACKGROUND: An increasing trend of oropharyngeal cancer (OPC) has been reported in several countries with different demographic characteristics, and often attributed to increases in human papillomavirus (HPV) infection. The survival of patients with OPC has steadily improved, especially for those with positive HPV status. This study assessed the incidence, trends, and survival of OPC in Aotearoa New Zealand (NZ) by age at diagnosis, sex and ethnicity. METHODS: The study included all 2109 patients resident in NZ with a primary diagnosis of oropharyngeal squamous cell carcinoma from 2006 to 2020, identified from the National Cancer Registry. We assessed age-standardised incidence rate (ASR), annual percent change (APC) and overall and relative survival rates. RESULTS: The average annual incidence of OPC was 2.2 per 100,000 population. There was a steady increase of 4.9% per year over 15 years. Although the incidence rates were higher in males over the study period, the overall rate of increase was similar in males (4.9%) and in females (4.3%). The incidence was highest in the 50-69-year group (8.8/100,000 population). This age group had an incidence that increased by 7.5% per year to 2018, and then declined. The main increase in rates was seen between the birth cohort of 1946-50 and that of 1956-60. The increase in incidence was seen in Maori and Pakeha/European populations, but no increase was seen in Pacific or Asian populations. The 5-year overall relative survival rate improved from 69% in 2006-13 to 78% in 2014-20. Survival rates were lower in older patients, females, and Maori patients. CONCLUSION: This study confirmed a substantial increase in OPC incidence in NZ, with some evidence to suggest a recent slowing in this increase. Maori and Pakeha/European had the highest incidence, while Pacific and Asian populations showed the lowest rates and no increase over the study period. Survival rates have improved over time, but remained lower in some demographic groups.

Association between melanoma thickness, clinical skin examination and socioeconomic status: results of a large population-based study.

Survival from melanoma is inversely related to tumour thickness and is less favorable for those in lower socioeconomic (SES) strata. Reasons for this are unclear but may relate to a lower prevalence of skin screening. Our aim was to examine the association between melanoma thickness, individual-level SES and clinical skin examination (CSE) using a population-based case-control study. Cases were Queensland (Australia) residents aged 20-75 years with a histologically confirmed first primary invasive cutaneous melanoma diagnosed between January 2000 and December 2003. Telephone interviews were completed by 3,762 cases (77.7%) and 3,824 (50.4%) controls. Thickness was dichotomized to thin (≤2 mm) and thick (>2 mm). Compared with controls, the risk of thick melanoma was significantly increased among men [relative risk ratio (RRR) = 1.56, 95% CI = 1.22-2.00], older participants (RRR = 1.76, 95% CI = 1.10-2.82), those educated to primary level (RRR = 1.70, 95% CI = 1.08-2.66), not married/living as married (RRR = 1.47, 95% CI = 1.15-1.88), retired (RRR = 1.39, 95% CI = 1.01-1.94) and not having a CSE in past 3 years (RRR = 1.45, 95% CI = 1.12-1.86). There was a significant trend to increasing prevalence of CSE with higher education (p < 0.01) and the benefit of CSE in reducing the risk of thick melanoma was most pronounced among that subgroup. There were no significant associations between cases with thin melanoma and controls. Melanoma thickness at presentation is significantly associated with educational level, other measures of SES and absence of CSE. Public health education efforts should focus on identifying new avenues that specifically target those subgroups of the population who are at increased risk of being diagnosed with thick melanoma.