Performance of cardiovascular disease risk prediction equations in more than 14 000 survivors of cancer in New Zealand primary care: a validation study.

BACKGROUND: People with cancer have an increased risk of cardiovascular disease. Risk prediction equations developed in New Zealand accurately predict 5-year cardiovascular disease risk in a general primary care population in the country. We assessed the performance of these equations for survivors of cancer in New Zealand. METHODS: For this validation study, patients aged 30-74 years from the PREDICT open cohort study, which was used to develop the New Zealand cardiovascular disease risk prediction equations, were included in the analysis if they had a primary diagnosis of invasive cancer at least 2 years before the date of the first cardiovascular disease risk assessment. The risk prediction equations are sex-specific and include the following predictors: age, ethnicity, socioeconomic deprivation index, family history of cardiovascular disease, smoking status, history of atrial fibrillation and diabetes, systolic blood pressure, total cholesterol to HDL cholesterol ratio, and preventive pharmacotherapy (blood-pressure-lowering, lipid-lowering, and antithrombotic drugs). Calibration was assessed by comparing the mean predicted 5-year cardiovascular disease risk, estimated using the risk prediction equations, with the observed risk across deciles of risk, for men and women, and according to the three clinical 5-year cardiovascular disease risk groups in New Zealand guidelines (<5%, 5% to <15%, and ≥15%). Discrimination was assessed by Harrell's C statistic. FINDINGS: 14 263 patients were included in the study. The mean age was 61 years (SD 9) for men and 60 years (SD 8) for women, with a median follow-up of 5·8 years for men and 5·7 years for women. The observed cardiovascular disease risk was underpredicted by a maximum of 2·5% in male and 3·2% in female decile groups. When patients were grouped according to clinical risk groups, observed cardiovascular disease risk was underpredicted by less than 2% in the lower risk groups and overpredicted by 2·2% for men and 3·3% for women in the highest risk group. Harrell's C statistics were 0·67 (SE 0·01) for men and 0·73 (0·01) for women. INTERPRETATION: The New Zealand cardiovascular disease risk prediction equations reasonably predicted the observed 5-year cardiovascular disease risk in survivors of cancer in the country, in whom risk prediction was considered clinically appropriate. Prediction could be improved by adding cancer-specific variables and considering competing risks. Our findings suggest that the equations are reasonable clinical tools for use in survivors of cancer in New Zealand. FUNDING: Auckland Medical Research Foundation, Health Research Council of New Zealand.

Beta-blocker use and breast cancer outcomes: a meta-analysis.

PURPOSE: Beta blockers (BBs) are commonly used cardiovascular medications, and their association with breast cancer outcomes has been examined in several previous observational studies and meta-analyses. In this study, an updated meta-analysis was undertaken to ascertain the association between BBs and both breast cancer death (BCD) and breast cancer recurrence (BCR). METHODS: Articles were sourced from various databases up until the 14th of August 2023. Effect estimates were pooled using the random effects model, and the Higgins I2 statistic was computed to ascertain heterogeneity. Subgroup analyses were conducted by the potential for immortal time bias (ITB), the exposure period (prediagnosis vs postdiagnosis), and type of BB (selective vs non-selective). Publication bias was assessed using funnel plots and Egger's regression tests. RESULTS: Twenty-four studies were included. Pooled results showed that there was no statistically significant association between BB use and both BCD (19 studies, hazard ratio = 0.90, 95% CI 0.78-1.04) and BCR (16 studies, HR = 0.87, 95% CI 0.71-1.08). After removing studies with ITB, the associations were attenuated towards the null. There was no effect modification for either outcome when stratifying by the exposure period or type of BB. There was clear evidence of publication bias for both outcomes. CONCLUSION: In this meta-analysis, we found no evidence of an association between BB use and both BCD and BCR. Removing studies with ITB attenuated the associations towards the null, but there was no effect modification by the exposure period or type of BB.

Post-diagnostic statin use and breast cancer-specific mortality: a population-based cohort study.

PURPOSE: Statins are the most widely prescribed cholesterol lowering medications and have been associated with both improved and unchanged breast cancer outcomes in previous studies. This study examines the association between the post-diagnostic use of statins and breast cancer outcomes (death and recurrence) in a large, representative sample of New Zealand (NZ) women with breast cancer. METHODS: Women diagnosed with a first primary breast cancer between 2007 and 2016 were identified from four population-based regional NZ breast cancer registries and linked to national pharmaceutical data, hospital discharges, and death records. Cox proportional hazard models were used to estimate the hazard of breast cancer-specific death (BCD) associated with any post-diagnostic statin use. RESULTS: Of the 14,976 women included in analyses, 27% used a statin after diagnosis and the median follow up time was 4.51 years. Statin use (vs non-use) was associated with a statistically significant decreased risk of BCD (adjusted hazard ratio: 0.74; 0.63-0.86). The association was attenuated when considering a subgroup of 'new' statin users (HR: 0.91; 0.69-1.19), however other analyses revealed that the protective effect of statins was more pronounced in estrogen receptor positive patients (HR: 0.77; 0.63-0.94), postmenopausal women (HR: 0.74; 0.63-0.88), and in women with advanced stage disease (HR: 0.65; 0.49-0.84). CONCLUSION: In this study, statin use was associated with a statistically significant decreased risk of breast cancer death, with subgroup analyses revealing a more protective effect in ER+ patients, postmenopausal women, and in women with advanced stage disease. Further research is warranted to determine if these associations are replicated in other clinical settings.

Receipt of mastectomy and adjuvant radiotherapy following breast conserving surgery (BCS) in New Zealand women with BCS-eligible breast cancer, 2010-2015: an observational study focusing on ethnic differences.

BACKGROUND: Women with early breast cancer who meet guideline-based criteria should be offered breast conserving surgery (BCS) with adjuvant radiotherapy as an alternative to mastectomy. New Zealand (NZ) has documented ethnic disparities in screening access and in breast cancer treatment pathways. This study aimed to determine whether, among BCS-eligible women, rates of receipt of mastectomy or radiotherapy differed by ethnicity and other factors. METHODS: The study assessed management of women with early breast cancer (ductal carcinoma in situ [DCIS] and invasive stages I-IIIA) registered between 2010 and 2015, extracted from the recently consolidated New Zealand Breast Cancer Registry (now Te Rehita Mate Utaetae NZBCF National Breast Cancer Register). Specific criteria were applied to determine women eligible for BCS. Uni- and multivariable analyses were undertaken to examine differences by demographic and clinicopathological factors with a primary focus on ethnicity (Maori, Pacific, Asian, and Other; the latter is defined as NZ European, Other European, and Middle Eastern Latin American and African). RESULTS: Overall 22.2% of 5520 BCS-eligible women were treated with mastectomy, and 91.1% of 3807 women who undertook BCS received adjuvant radiotherapy (93.5% for invasive cancer, and 78.3% for DCIS). Asian ethnicity was associated with a higher mastectomy rate in the invasive cancer group (OR 2.18; 95%CI 1.72-2.75), compared to Other ethnicity, along with older age, symptomatic diagnosis, advanced stage, larger tumour, HER2-positive, and hormone receptor-negative groups. Pacific ethnicity was associated with a lower adjuvant radiotherapy rate, compared to Other ethnicity, in both invasive and DCIS groups, along with older age, symptomatic diagnosis, and lower grade tumour in the invasive group. Both mastectomy and adjuvant radiotherapy rates decreased over time. For those who did not receive radiotherapy, non-referral by a clinician was the most common documented reason (8%), followed by patient decline after being referred (5%). CONCLUSION: Rates of radiotherapy use are high by international standards. Further research is required to understand differences by ethnicity in both rates of mastectomy and lower rates of radiotherapy after BCS for Pacific women, and the reasons for non-referral by clinicians.

Comparison of Cancer Mortality and Incidence Between New Zealand and Australia and Reflection on Differences in Cancer Care: An Ecological Cross-Sectional Study of 2014-2018.

BACKGROUND: Despite many background similarities, New Zealand showed excess cancer deaths compared to Australia in previous studies. This study extends this comparison using the most recent data of 2014-2018. METHODS: This study used publicly available cancer mortality and incidence data of New Zealand Ministry of Health and Australian Institute of Health and Welfare, and resident population data of Statistics New Zealand. Australian cancer mortality and incidence rates were applied to New Zealand population, by site of cancer, year, age and sex, to estimate the expected numbers, which were compared with the New Zealand observed numbers. RESULTS: For total cancers in 2014-2018, New Zealand had 780 excess deaths in women (17.1% of the annual total 4549; 95% confidence interval (CI) 15.8-18.4%), and 281 excess deaths in men (5.5% of the annual total 5105; 95% CI 4.3-6.7%) compared to Australia. The excess was contributed by many major cancers including colorectal, melanoma, and stomach cancer in both sexes; lung, uterine, and breast cancer in women, and prostate cancer in men. New Zealand's total cancer incidences were lower than those expected from Australia's in both women and men: average annual difference of 419 cases (-3.6% of the annual total 11 505; 95% CI -4.5 to -2.8%), and 1485 (-11.7% of the annual total 12 669; 95% CI -12.5 to -10.9%), respectively. Comparing time periods, the excesses in total cancer deaths in women were 15.1% in 2000-07, and 17.5% in 1996-1997; and in men 4.7% in 2000-2007 and 5.6% in 1996-1997. The differences by time period were non-significant. CONCLUSION: Excess mortality from all cancers combined and several common cancers in New Zealand, compared to Australia, persisted in 2014-2018, being similar to excesses in 2000-2007 and 1996-1997. It cannot be explained by differences in incidence, but may be attributable to various aspects of health systems governance and performance.

Post-diagnostic beta blocker use and breast cancer-specific mortality: a population-based cohort study.

PURPOSE: Beta blockers (BB) have been associated with improved, worsened, or unchanged breast cancer outcomes in previous studies. This study examines the association between the post-diagnostic use of BBs and death from breast cancer in a large, representative sample of New Zealand (NZ) women with breast cancer. METHODS: Women diagnosed with a first primary breast cancer between 2007 and 2016 were identified from four population-based regional NZ breast cancer registries and linked to national pharmaceutical data, hospital discharges, and death records. The median follow-up time was 4.51 years. Cox proportional hazard models were used to estimate the hazard of breast cancer-specific death (BCD) associated with any post-diagnostic BB use. RESULTS: Of the 14,976 women included in analyses, 21% used a BB after diagnosis. BB use (vs non-use) was associated with a small and nonstatistically significant increased risk of BCD (adjusted hazard ratio: 1.11; 95% CI 0.95-1.29). A statistically significant increased risk confined to short-term use (0-3 months) was seen (HR = 1.40; 1.14-1.73), and this risk steadily decreased with increasing duration of use and became a statistically significant protective effect at 3 + years of use (HR = 0.55; 0.34-0.88). CONCLUSION: Our findings suggest that any increased risk associated with BB use may be driven by risk in the initial few months of use. Long-term BB use may be associated with a reduction in BCD.

Development and validation of a predictive model for estimating EGFR mutation probabilities in patients with non-squamous non-small cell lung cancer in New Zealand.

BACKGROUND: Targeted treatment with Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitors (TKIs) is superior to systemic chemotherapy in non-small cell lung cancer (NSCLC) patients with EGFR gene mutations. Detection of EGFR mutations is a challenge in many patients due to the lack of suitable tumour specimens for molecular testing or for other reasons. EGFR mutations are more common in female, Asian and never smoking NSCLC patients. METHODS: Patients were from a population-based retrospective cohort of 3556 patients diagnosed with non-squamous non-small cell lung cancer in northern New Zealand between 1 Feb 2010 and 31 July 2017. A total of 1694 patients were tested for EGFR mutations, of which information on 1665 patients was available for model development and validation. A multivariable logistic regression model was developed based on 1176 tested patients, and validated in 489 tested patients. Among 1862 patients not tested for EGFR mutations, 129 patients were treated with EGFR-TKIs. Their EGFR mutation probabilities were calculated using the model, and their duration of benefit and overall survival from the start of EGFR-TKI were compared among the three predicted probability groups: < 0.2, 0.2-0.6, and > 0.6. RESULTS: The model has three predictors: sex, ethnicity and smoking status, and is presented as a nomogram to calculate EGFR mutation probabilities. The model performed well in the validation group (AUC = 0.75). The probability cut-point of 0.2 corresponds 68% sensitivity and 78% specificity. The model predictions were related to outcome in a group of TKI-treated patients with no biopsy testing available (n = 129); in subgroups with predicted probabilities of < 0.2, 0.2-0.6, and > 0.6, median overall survival times from starting EGFR-TKI were 4.0, 5.5 and 18.3 months (p = 0.02); and median times remaining on EGFR-TKI treatment were 2.0, 4.2, and 14.0 months, respectively (p < 0.001). CONCLUSION: Our model may assist clinical decision making for patients in whom tissue-based mutation testing is difficult or as a supplement to mutation testing.

Rapid increase in endometrial cancer incidence and ethnic differences in New Zealand.

PURPOSE: Endometrial cancer accounts for 3.9% of all female cancers globally, and its incidence appears to be increasing in women under 40 years of age. This paper investigated ethnic-specific trends in endometrial cancer across different age groups in New Zealand. METHODS: Women who were diagnosed with endometrial cancer between 1996 and 2012 were identified from the New Zealand Cancer Registry. Annual age-standardized incidence and mortality rates were calculated for each ethnicity (Maori, Pacific, and non-Maori non-Pacific) in four age groups (< 40, 40-49, 50-74, and 75 +). The estimates were adjusted for hysterectomy. Joinpoint regression analysis was used to assess trends over time and annual percentage changes (APCs) were estimated. RESULTS: Between 1996 and 2012, age-standardized incidence rates increased in all women and significantly in the < 40, 40-49, and 50-74 age groups (APC 9.22, 3.56, and 1.65 respectively). Incidence rates were highest in Pacific women and increased most rapidly in those under 50 years of age (APC 9.36). Conversely, age-standardized mortality rates decreased in all women and significantly in the 50-74 and 75 + age groups (APC - 5.25 and - 5.06 respectively), with the highest rate observed in Pacific women. CONCLUSION: Pacific women had the highest incidence of endometrial cancer and the trend was increasing, particularly in young women. This could be attributed, at least in part, to a high and increasing rate of obesity in these women and should be explored in future research.

Prognostic models for breast cancer: a systematic review.

BACKGROUND: Breast cancer is the most common cancer in women worldwide, with a great diversity in outcomes among individual patients. The ability to accurately predict a breast cancer outcome is important to patients, physicians, researchers, and policy makers. Many models have been developed and tested in different settings. We systematically reviewed the prognostic models developed and/or validated for patients with breast cancer. METHODS: We conducted a systematic search in four electronic databases and some oncology websites, and a manual search in the bibliographies of the included studies. We identified original studies that were published prior to 1st January 2017, and presented the development and/or validation of models based mainly on clinico-pathological factors to predict mortality and/or recurrence in female breast cancer patients. RESULTS: From the 96 articles selected from 4095 citations found, we identified 58 models, which predicted mortality (n = 28), recurrence (n = 23), or both (n = 7). The most frequently used predictors were nodal status (n = 49), tumour size (n = 42), tumour grade (n = 29), age at diagnosis (n = 24), and oestrogen receptor status (n = 21). Models were developed in Europe (n = 25), Asia (n = 13), North America (n = 12), and Australia (n = 1) between 1982 and 2016. Models were validated in the development cohorts (n = 43) and/or independent populations (n = 17), by comparing the predicted outcomes with the observed outcomes (n = 55) and/or with the outcomes estimated by other models (n = 32), or the outcomes estimated by individual prognostic factors (n = 8). The most commonly used methods were: Cox proportional hazards regression for model development (n = 32); the absolute differences between the predicted and observed outcomes (n = 30) for calibration; and C-index/AUC (n = 44) for discrimination. Overall, the models performed well in the development cohorts but less accurately in some independent populations, particularly in patients with high risk and young and elderly patients. An exception is the Nottingham Prognostic Index, which retains its predicting ability in most independent populations. CONCLUSIONS: Many prognostic models have been developed for breast cancer, but only a few have been validated widely in different settings. Importantly, their performance was suboptimal in independent populations, particularly in patients with high risk and in young and elderly patients.

In situ and invasive melanoma in a high-risk, New Zealand, population: A population-based study.

BACKGROUND: Few population-based studies assess both invasive and in situ melanoma. We document all patients with a first biopsied melanoma in a general population in New Zealand (NZ). METHODS: All residents in a defined area of New Zealand with a biopsy showing a new primary invasive or in situ melanoma from 2010 to 2012 were identified, 974 patients; analysis used multivariate methods. RESULTS: Age-standardised incidence rates were 34.3 in females (F) and 41.4 in males (M) for invasive, 20.9 F and 27.6 M for in situ, and 55.2 F and 69.0 M for total melanoma. More in situ melanoma occurred in older patients and on the head and neck. Geometric mean Breslow thickness for invasive was 0.78 mm F and 0.85 mm M, with thicker lesions at ages over 60 and on the lower limb; there was no significant relationship with sex, distance from care or social deprivation assessed from residential address. Nodular melanomas (15%) were more frequent in older and male patients, and on the limbs, and were thicker. The estimated cumulative risk for melanoma is 4.4% F and 4.6% M by age 70. The body site distribution and sex differences were consistent with sun exposure patterns. Estimated incidence of melanoma in New Zealand in 2018 is 2500 invasive and 1700 in situ cases. CONCLUSIONS: Assessing both in situ and invasive melanoma expands the clinical picture, better estimating health care demand and costs. Results suggest that in situ disease is a more slowly growing lesion than the early phase of invasive disease. The features of thicker or nodular melanoma show priorities for prevention and early detection.

Obesity and breast cancer outcomes in chemotherapy patients in New Zealand - a population-based cohort study.

BACKGROUND: Obesity has been reported as an adverse prognostic factor in breast cancer, but inconsistently, and under-treatment with chemotherapy may occur. We provide the first assessment of obesity and breast cancer outcomes in a population-based, multi-ethnic cohort of New Zealand patients treated with chemotherapy. METHODS: All 3536 women diagnosed with invasive breast cancer in the Waikato region of New Zealand from 2000-2014 were registered and followed until last follow-up in specialist or primary care, death or Dec 2014; median follow-up 4.1 years. For the 1049 patients receiving chemotherapy, mortality from breast cancer, other causes, and all causes, and rates of loco-regional and of distant recurrence, were assessed by body mass index (BMI), recorded after diagnosis, adjusting for other clinico-pathological and demographic factors by Cox regression. RESULTS: BMI was known for 98% (n=1049); 33% were overweight (BMI 25-29.9), 21% were obese (BMI 30-34.9), and 14% were very obese (BMI 35+). There were no significant associations between obesity and survival, after adjustment for demographic and clinical factors (hazard ratios, HR, for very obese compared to BMI 21-24, for breast cancer deaths 0.96 (0.56-1.67), and for all deaths 1.03 (0.63-1.67), respectively, and only small non-significant associations for loco-regional or metastatic recurrence rates (HR 1.17 and 1.33 respectively). Subgroup analyses by age, menopausal status, ethnicity, stage, post-surgical radiotherapy, mode of diagnosis, type of surgery, and receptor status, showed no associations. No associations were seen with BMI as a continuous variable. The results in all patients irrespective of treatment but with recorded BMI data (n=2296) showed similar results. CONCLUSIONS: In this population, obesity assessed post-diagnosis had no effect on survival or recurrence, based on 1049 patients with chemotherapy treatment with follow-up up to 14 years.

Development and validation of a new predictive model for breast cancer survival in New Zealand and comparison to the Nottingham prognostic index.

BACKGROUND: The only available predictive models for the outcome of breast cancer patients in New Zealand (NZ) are based on data in other countries. We aimed to develop and validate a predictive model using NZ data for this population, and compare its performance to a widely used overseas model, the Nottingham Prognostic Index (NPI). METHODS: We developed a model to predict 10-year breast cancer-specific survival, using data collected prospectively in the largest population-based regional breast cancer registry in NZ (Auckland, 9182 patients), and assessed its performance in this data set (internal validation) and in an independent NZ population-based series of 2625 patients in Waikato (external validation). The data included all women with primary invasive breast cancer diagnosed from 1 June 2000 to 30 June 2014, with follow up to death or Dec 31, 2014. We used multivariate Cox proportional hazards regression to assess predictors and to calculate predicted 10-year breast cancer mortality, and therefore survival, probability for each patient. We assessed observed survival by the Kaplan Meier method. We assessed discrimination by the C statistic, and calibration by comparing predicted and observed survival rates for patients in 10 groups ordered by predicted 10-year survival. We compared this NZ model with the Nottingham Prognostic Index (NPI) in this validation data set. RESULTS: Discrimination was good: C statistics were 0.84 for internal validity and 0.83 for an independent external validity. For calibration, for both internal and external validity the predicted 10-year survival probabilities in all groups of patients, ordered by predicted survival, were within the 95% confidence intervals (CI) of the observed Kaplan-Meier survival probabilities. The NZ model showed good discrimination even within the prognostic groups defined by the NPI. CONCLUSIONS: These results for the New Zealand model show good internal and external validity, transportability, and potential clinical value of the model, and its clear superiority over the NPI. Further research is needed to assess other potential predictors, to assess the model's performance in specific subgroups of patients, and to compare it to other models, which have been developed in other countries and have not yet been tested in NZ.

Ethnic disparities in breast cancer survival in New Zealand: which factors contribute?

BACKGROUND: New Zealand has major ethnic disparities in breast cancer survival with Maori (indigenous people) and Pacific women (immigrants or descended from immigrants from Pacific Islands) faring much worse than other ethnic groups. This paper identified underlying factors and assessed their relative contribution to this risk differential. METHODS: This study involved all women who were diagnosed with primary invasive breast cancer in two health regions, covering about 40% of the national population, between January 2000 and June 2014. Maori and Pacific patients were compared with other ethnic groups in terms of demographics, mode of diagnosis, disease factors and treatment factors. Cox regression modelling was performed with stepwise adjustments, and hazards of excess mortality from breast cancer for Maori and Pacific patients were assessed. RESULTS: Of the 13,657 patients who were included in this analysis, 1281 (9.4%) were Maori, and 897 (6.6%) were Pacific women. Compared to other ethnic groups, they were younger, more likely to reside in deprived neighbourhoods and to have co-morbidities, and less likely to be diagnosed through screening and with early stage cancer, to be treated in a private care facility, to receive timely cancer treatment, and to receive breast conserving surgery. They had a higher risk of excess mortality from breast cancer (age and year of diagnosis adjusted hazard ratio: 1.76; 95% CI: 1.51-2.04 for Maori and 1.97; 95% CI: 1.67-2.32 for Pacific women), of which 75% and 99% respectively were explained by baseline differences. The most important contributor was late stage at diagnosis. Other contributors included neighbourhood deprivation, mode of diagnosis, type of health care facility where primary cancer treatment was undertaken and type of loco-regional therapy. CONCLUSIONS: Late diagnosis, deprivation and differential access to and quality of cancer care services were the key contributors to ethnic disparities in breast cancer survival in New Zealand. Our findings underscore the need for a greater equity focus along the breast cancer care pathway, with an emphasis on improving access to early diagnosis for Maori and Pacific women.

Risk of cardiovascular disease in cancer survivors: A cohort study of 446,384 New Zealand primary care patients.

BACKGROUND: Given advances in the management of cancer, it is increasingly important for clinicians to appropriately manage the risk of cardiovascular disease (CVD) among cancer survivors. It is unclear whether CVD risk is increased among cancer survivors overall, and there is inconsistency in evidence to date about CVD incidence and mortality by cancer type. METHODS: Patients aged 30-74 years entered an open cohort study at the time of first CVD risk assessment, between 2004 and 2018, in primary care in New Zealand. Patients with established CVD or cancer within 2 years prior to study entry were excluded. Cancer diagnosis (1995-2016) was determined from a national cancer registry. Cause-specific hazard models were used to examine the association between history of cancer and two outcomes: (1) CVD-related hospitalization and/or death and (2) CVD death. RESULTS: The study included 446,384 patients, of whom 14,263 (3.2%) were cancer survivors. Risk of CVD hospitalization and/or death was increased among cancer survivors compared with patients without cancer at cohort entry (multivariable-adjusted hazard ratio, mHR, 1.11, 95% CI 1.05-1.18), more so for CVD death (1.31, 1.14-1.52). Risk of CVD hospitalization and/or death was increased in patients with myeloma (2.66, 1.60-4.42), lung cancer (2.19, 1.48-3.24) and non-Hodgkin lymphoma (1.90, 1.42-2.54), but not for some cancers (e.g., colorectal, 0.87, 0.71-1.06). Risk of CVD death was increased in several cancer types including melanoma (1.73, 1.25-2.38) and breast cancer (1.56, 1.16-2.11). CONCLUSION: CVD risk management needs to be prioritized among cancer survivors overall, and particularly in those with myeloma, lung cancer and non-Hodgkin lymphoma given consistent evidence of increased risk.

Microwaves in the cold war: the Moscow embassy study and its interpretation. Review of a retrospective cohort study.

BACKGROUND: From 1953 to 1976, beams of microwaves of 2.5 to 4.0 GHz were aimed at the US embassy building in Moscow. An extensive study investigated the health of embassy staff and their families, comparing Moscow embassy staff with staff in other Eastern European US embassies. The resulting large report has never been published in peer reviewed literature. METHODS: The original report and other published comments or extracts from the report were reviewed. RESULTS: The extensive study reports on mortality and morbidity, recorded on medical records and by regular examinations, and on self-reported symptoms. Exposure levels were low, but similar or greater than present-day exposures to radiofrequencies sources such as cell phone base stations. The conclusions were that no adverse health effects of the radiation were shown. The study validity depends on the assumption that staff at the other embassies were not exposed to similar radiofrequencies. This has been questioned, and other interpretations of the data have been presented. CONCLUSIONS: The conclusions of the original report are supported. Contrary conclusions given in some other reports are due to misinterpretation of the results.

Nitrates in drinking water and cancers of the colon and rectum: a meta-analysis of epidemiological studies.

BACKGROUND: some recent studies have suggested that the risks of colon and rectal cancer increase with exposure to higher concentrations of nitrates in drinking water. This study is a meta-analysis of relevant studies. METHODS: literature published up to June 2021 was accessed and final results abstracted. Two cohort studies and seven case-control studies were analysed, and one case-control study not used because of limited data. Mixed effects meta-regression analysis was used to assess trends in colon cancer, rectal cancer, and colon cancer considered together, with nitrate concentrations in drinking water. RESULTS: The usually accepted exposure upper limit for nitrates is 11.3 mg/l NO3-N. However most studies assess a lower range, with only one study providing data over 8 mg/l. Colorectal cancer risk increased by 2.4% (95% limits 0.4-4.5%) per unit increase in nitrate concentration, over a range from very low values to mid-range values. Extrapolation to higher dosages has insufficient data. The trend for rectal cancer is less than that for colon cancer. CONCLUSION: The increase in colorectal cancer risk with increasing nitrate concentration is lower than in some recent studies, and applies only over a small range. Extrapolation of these results to higher nitrate levels is not warranted. The studies vary greatly in their design, the nitrate concentrations assessed, and in their results. This association is weak and inconsistent, and may be influenced by bias and confounding factors. Any association of drinking water nitrates with colorectal cancer risk is small, and is uncertain.

Cancer of the nasopharynx in Aotearoa New Zealand from 1994 to 2018: Incidence and survival in a population-based, national registry cohort study.

Background: Cancer of the nasopharynx has remarkable geographic and ethnic variation in incidence and outcomes globally. Recent advances in diagnostic and therapeutic technologies provide new opportunities for early detection and improved outcomes. This study aimed to determine the incidence, demographics, outcomes and time trends of cancer of the nasopharynx in Aotearoa New Zealand over the last 25 years. Methods: In a population-based, national registry cohort study of notifications of malignant neoplasms of the nasopharynx made to the New Zealand Cancer Registry between 1994 and 2018, age-specific and age-standardised incidence rates and survival outcomes were evaluated. Findings: 577 registrations of nasopharyngeal cancer from between 1994 and 2018 were analysed; median age at diagnosis 54 years; 72.4% male; 37.4% Asian, 24.3% New Zealand European, 25.3% Pacific peoples, 13.0% Maori. Age-standardised annual incidence remained low (<1/100,000 person-years) and stable from 1994 to 2018. Age-standardised incidence rates in Pacific peoples, Asian and Maori were 21 (95% CI 12.07-35.21)-, 17 (10.95-25.33)- and 4 (2.79-7.07)-fold higher, respectively, than New Zealand Europeans. Epstein-Barr virus-related morphologies predominated keratinising squamous cell carcinoma and not-otherwise-specified morphological subtypes. Ten-year overall survival rate for the cohort was 49.2% (95% CI 44.7-53.5). Older age at diagnosis (65-94 years), Maori or Pacific ethnicity, keratinising squamous cell carcinoma and distant disease were associated with shorter overall survival, whereas younger age at diagnosis (10-29 years), and Asian ethnicity were associated with longer survival. Interpretation: Aotearoa New Zealand has a distinct profile of nasopharyngeal cancer, with age, ethnicity and morphology among the main determinants of incidence and survival. Funding: None.

Trends in brain cancers (glioma) in New Zealand from 1995 to 2020, with reference to mobile phone use.

BACKGROUND: Some case-control studies have suggested substantial increased risks of glioma in association with mobile phone use; these risks would lead to an increase in incidence over time. METHODS: Incidence rates of glioma from 1995 to 2020 by age, sex, and site in New Zealand (NZ) recorded by the national cancer registry were assessed and trends analysed. Phone use was based on surveys. RESULTS: In these 25 years there were 6677 incident gliomas, giving age-standardised rates (WHO world standard) of 6.04 in males, and 3.95 in females per 100,000. The use of mobile phones increased rapidly from 1990 to more than 50% of the population from about 2000, and almost all the population from 2006. The incidence of glioma from ages 10-69 has shown a small decrease over the last 25 years, during which time the use of mobile phones has become almost universal. Rates in the brain locations receiving most radiofrequency energy have also shown a small decrease. Rates at ages of 80 and over have increased. CONCLUSION: There is no indication of any increase related to the use of mobile phones. These results are similar to results in Australia and in many other countries. The increase in recorded incidence at ages over 80 is similar to that seen in other countries and consistent with improved diagnostic methods.

Biologic markers of sun exposure and melanoma risk in women: pooled case-control analysis.

A model has been proposed whereby melanomas arise through two distinct pathways dependent on the relative influence of host susceptibility and sun exposure. Such pathways may explain site-specific patterns of melanoma occurrence. To explore this model, we investigated the relationship between melanoma risk and general markers of acute (recalled sunburns) and chronic (prevalent solar keratoses) sun exposure, stratified by anatomic site and host phenotype. Our working hypothesis was that head and neck melanomas have stronger associations with solar keratoses and weaker associations with sunburn than trunk melanomas. We conducted a collaborative analysis using original data from women subjects of 11 case-control studies of melanoma (2,575 cases, 3,241 controls). We adjusted for potential confounding effects of sunlamp use and sunbathing. The magnitude of sunburn associations did not differ significantly by melanoma site, nevus count or histologic subtype of melanoma. Across all sites, relative risk of melanoma increased with an increasing number of reported lifetime "painful" sunburns, lifetime "severe" sunburns and "severe" sunburns in youth (p(trend) < 0.001), with pooled odds ratios (pORs) for the highest category of sunburns versus no sunburns of 3.22 [95% confidence interval (CI) 2.04-5.09] for lifetime "painful" sunburns, 2.10 (95%CI 1.30-3.38) for lifetime "severe" sunburns and 2.43 (95%CI 1.61-3.65) for "severe" sunburns in youth. Solar keratoses strongly increased the risk of head and neck melanoma (pOR 4.91, 95%CI 2.10-11.46), but data were insufficient to assess risk for other sites. Reported sunburn is strongly associated with melanoma on all major body sites.

Population-based incidence rates and increased risk of EGFR mutated non-small cell lung cancer in Maori and Pacifica in New Zealand.

BACKGROUND: Non-squamous non-small cell lung cancer (NSCLC) patients with Epidermal Growth Factor Receptor (EGFR) mutation benefit from targeted treatments. Previous studies reported EGFR mutation-positive proportions among tested non-squamous NSCLC patients. However, incidence rates and population risk of EGFR mutation-positive and EGFR mutation-negative non-squamous NSCLC have not been assessed. This study therefore aimed to estimate the population-based incidence rates of EGFR mutation-positive and EGFR mutation-negative non-squamous NSCLC in different population groups defined by sex, ethnic group and smoking status. METHODS: This study included data from all non-squamous NSCLC patients diagnosed in northern New Zealand between 1/02/2010 and 31/07/2017 (N = 3815), obtained from a population-based cancer registry. Age-specific incidence rates, WHO age-standardised rates (ASRs) and rates adjusted for incomplete testing were calculated for EGFR mutation-positive and EGFR mutation-negative diseases for the study cohort as a whole and subgroups of patients. RESULTS: Among 3815 patients, 45% were tested for EGFR mutations; 22.5% of those tested were EGFR mutation-positive. The ASR of EGFR mutation-positive NSCLC was 5.05 (95%CI 4.71-5.39) per 100,000 person-years. ASRs for EGFR mutation-positive NSCLC were higher for females than males: standardised incidence ratio (SIR) 1.50 (1.31-1.73); higher for Pacifica, Asians and Maori compared with New Zealand Europeans: SIRs 3.47 (2.48-4.85), 3.35 (2.62-4.28), and 2.02 (1.43-2.87), respectively; and, only slightly increased in ever-smokers compared with never-smokers: SIR 1.25 (1.02-1.53). In contrast, the ASR of EGFR mutation-negative NSCLC was 17.39 (16.75-18.02) per 100,000 person-years, showing a strong association with smoking; was higher for men; highest for Maori, followed by Pacifica and then New Zealand Europeans, and lowest for Asians. When corrected for incomplete testing, SIRs by sex, ethnicity and smoking, for both diseases, remained similar to those based on tested patients. CONCLUSION: The population risk of EGFR mutation-positive NSCLC was significantly higher for Maori and Pacifica compared with New Zealand Europeans.