Age-related differences in cancer relative survival in the United States: A SEER-18 analysis.

Cancer survival has improved since the 1990s, but to different extents across age groups, with a disadvantage for older adults. We aimed to quantify age-related differences in relative survival (RS-1-year and 1-year conditioning on surviving 1 year) for 10 common cancer types by stage at diagnosis. We used data from 18 United States Surveillance Epidemiology and End Results cancer registries and included cancers diagnosed in 2012 to 2016 followed until December 31, 2017. We estimated absolute differences in RS between the 50 to 64 age group and the 75 to 84 age group. The smallest differences were observed for prostate and breast cancers (1.8%-points [95% confidence interval (CI): 1.5-2.1] and 1.9%-points [95% CI: 1.5-2.3], respectively). The largest was for ovarian cancer (27%-points, 95% CI: 24-29). For other cancers, differences ranged between 7 (95% CI: 5-9, esophagus) and 18%-points (95% CI: 17-19, pancreas). Except for pancreatic cancer, cancer type and stage combinations with very high (>95%) or very low (<40%) 1-year RS tended to have smaller age-related differences in survival than those with mid-range prognoses. Age-related differences in 1-year survival conditioning on having survived 1-year were small for most cancer and stage combinations. The broad variation in survival differences by age across cancer types and stages, especially in the first year, age-related differences in survival are likely influenced by amenability to treatment. Future work to measure the extent of age-related differences that are avoidable, and identify how to narrow the survival gap, may have most benefit by prioritizing cancers with relatively large age-related differences in survival (eg, stomach, esophagus, liver and pancreas).

Combining faecal immunochemical testing with blood test results for colorectal cancer risk stratification: a consecutive cohort of 16,604 patients presenting to primary care.

BACKGROUND: Faecal immunochemical tests (FITs) are used to triage primary care patients with symptoms that could be caused by colorectal cancer for referral to colonoscopy. The aim of this study was to determine whether combining FIT with routine blood test results could improve the performance of FIT in the primary care setting. METHODS: Results of all consecutive FITs requested by primary care providers between March 2017 and December 2020 were retrieved from the Oxford University Hospitals NHS Foundation Trust. Demographic factors (age, sex), reason for referral, and results of blood tests within 90 days were also retrieved. Patients were followed up for incident colorectal cancer in linked hospital records. The sensitivity, specificity, positive and negative predictive values of FIT alone, FIT paired with blood test results, and several multivariable FIT models, were compared. RESULTS: One hundred thirty-nine colorectal cancers were diagnosed (0.8%). Sensitivity and specificity of FIT alone at a threshold of 10 µg Hb/g were 92.1 and 91.5% respectively. Compared to FIT alone, blood test results did not improve the performance of FIT. Pairing blood test results with FIT increased specificity but decreased sensitivity. Multivariable models including blood tests performed similarly to FIT alone. CONCLUSIONS: FIT is a highly sensitive tool for identifying higher risk individuals presenting to primary care with lower risk symptoms. Combining blood test results with FIT does not appear to lead to better discrimination for colorectal cancer than using FIT alone.

Risk of contralateral breast cancer according to first breast cancer characteristics among women in the USA, 1992-2016.

BACKGROUND: Estimates of contralateral breast cancer (CBC) risk in the modern treatment era by year of diagnosis and characteristics of the first breast cancer are needed to assess the impact of recent advances in breast cancer treatment and inform clinical decision making. METHODS: We examined CBC risk among 419,818 women (age 30-84 years) who were diagnosed with a first unilateral invasive breast cancer and survived ≥ 1 year in the US Surveillance, Epidemiology, and End Results program cancer registries from 1992 to 2015 (follow-up through 2016). CBC was defined as a second invasive breast cancer in the contralateral breast ≥ 12 months after the first breast cancer. We estimated standardized incidence ratios (SIRs) of CBC by year of diagnosis, age at diagnosis, and tumor characteristics for the first breast cancer. Cumulative incidence of CBC was calculated for women diagnosed with a first breast cancer in the recent treatment era (2004-2015, follow-up through 2016). RESULTS: Over a median follow-up of 8 years (range 1-25 years), 12,986 breast cancer patients developed CBC. Overall, breast cancer patients had approximately twice the risk of developing cancer in the contralateral breast when compared to that expected in the general population (SIR = 2.21, 95% CI = 2.17-2.25). SIRs for CBC declined by year of first diagnosis, irrespective of age at diagnosis and estrogen receptor (ER) status (p-trends < 0.001), but the strongest decline was after an ER-positive tumor. The 5-year cumulative incidence of CBC ranged from 1.01% (95% CI = 0.90-1.14%) in younger women (age < 50 years) with a first ER-positive tumor to 1.89% (95% CI = 1.61-2.21%) in younger women with a first ER-negative tumor. CONCLUSION: Declines in CBC risk are consistent with continued advances in breast cancer treatment. The updated estimates of cumulative incidence inform breast cancer patients and clinicians on the risk of CBC and may help guide treatment decisions.

Nonmalignant meningioma and vestibular schwannoma incidence trends in the United States, 2004-2017.

BACKGROUND: Given concerns about risks associated with the growing use of mobile phones over recent decades, the authors analyzed temporal trends in incidence rates of nonmalignant meningioma and vestibular schwannoma in the United States. METHODS: The incidence of nonmalignant meningioma and vestibular schwannoma among adults in the Surveillance, Epidemiology, and End Results 18 registries during 2004 through 2017 was evaluated according to the method of diagnosis: microscopically (MC) or radiographically confirmed (RGC). Annual percent changes (APCs) and 95% CIs were estimated using log-linear models. RESULTS: Overall meningioma rates (n = 108,043) increased significantly from 2004 to 2009 (APC, 5.4%; 95% CI, 4.4%-6.4%) but subsequently rose at a slower pace through 2017 (APC, 1.0%; 95% CI, 0.6%-1.5%). Rates for MC meningiomas changed little from 2004 to 2017 (APC, -0.3%; 95% CI, -0.7%, 0.1%) but rose rapidly for RGC meningiomas until 2009 (APC, 9.5%; 95% CI, 7.8%-11.1%) and rose more modestly thereafter (APC, 2.3%; 95% CI, 1.5%-3.0%). Overall vestibular schwannoma rates (n = 17,475) were stable (APC, 0.4%; 95% CI, -0.2%, 1.0%), but MC vestibular schwannoma rates decreased (APC, -1.9%; 95% CI, -2.7%, -1.1%), whereas RGC vestibular schwannoma rates rose (2006-2017: APC, 1.7%; 95% CI, 0.5%-3.0%). For each tumor, the trends by diagnostic method were similar for each sex and each racial/ethnic group, but RGC diagnosis was more likely in older patients and for smaller tumors. Meningioma trends and the proportion of RGC diagnoses varied notably by registry. CONCLUSIONS: Overall trends obscured differences by diagnostic method in this first large, detailed assessment, but the recent stable rates argue against an association with mobile phone use. Variation among registries requires evaluation to improve the registration of these nonmalignant tumors. LAY SUMMARY: The etiology of most benign meningiomas and vestibular schwannomas is poorly understood, but concerns have been raised about whether mobile phone use contributes to risk of developing these tumors. Descriptive studies examining temporal trends could provide insight; however, globally, few registries collect these nonmalignant cases. In the United States, reporting benign meningiomas and vestibular schwannomas became required by law in 2004. This was the first large, systematic study to quantify and characterize incidence trends for meningioma and vestibular schwannoma according to whether the tumors were diagnosed microscopically or only radiographically. Differential trends across registries and by diagnostic method suggest that caution should be used when interpreting the patterns.

Leading cancers contributing to educational disparities in cancer mortality in the US, 2017.

PURPOSE: To inform prevention efforts, we sought to determine which cancer types contribute the most to cancer mortality disparities by individual-level education using national death certificate data for 2017. METHODS: Information on all US deaths occurring in 2017 among 25-84-year-olds was ascertained from national death certificate data, which include cause of death and educational attainment. Education was classified as high school or less (≤ 12 years), some college or diploma (13-15 years), and Bachelor's degree or higher (≥ 16 years). Cancer mortality rate differences (RD) were calculated by subtracting age-adjusted mortality rates (AMR) among those with ≥ 16 years of education from AMR among those with ≤ 12 years. RESULTS: The cancer mortality rate difference between those with a Bachelor's degree or more vs. high school or less education was 72 deaths per 100,000 person-years. Lung cancer deaths account for over half (53%) of the RD for cancer mortality by education in the US. CONCLUSION: Efforts to reduce smoking, particularly among persons with less education, would contribute substantially to reducing educational disparities in lung cancer and overall cancer mortality.

Association of lifestyle and clinical characteristics with receipt of radiotherapy treatment among women diagnosed with DCIS in the NIH-AARP Diet and Health Study.

PURPOSE: The long-term risks and benefits of radiotherapy for ductal carcinoma in situ (DCIS) remain unclear. Recent data from the Surveillance, Epidemiology and End Results (SEER) registries showed that DCIS-associated radiotherapy treatment significantly increased risk of second non-breast cancers including lung cancer. To help understand those observations and whether breast cancer risk factors are related to radiotherapy treatment decision-making, we examined associations between lifestyle and clinical factors with DCIS radiotherapy receipt. METHODS: Among 1628 participants from the NIH-AARP Diet and Health Study, diagnosed with incident DCIS (1995-2011), we examined associations between lifestyle and clinical factors with radiotherapy receipt. Radiotherapy and clinical information were ascertained from state cancer registries. Odds ratios (ORs) and 95% confidence intervals (CIs) for radiotherapy receipt (yes/no) were estimated from multivariable logistic regression. RESULTS: Overall, 45% (n = 730) received radiotherapy. No relationships were observed for most lifestyle factors and radiotherapy receipt, including current smoking (OR 0.97, 95%CI 0.70, 1.34). However positive associations were observed for moderate alcohol consumption and infrequent physical activity. The strongest associations were observed for radiotherapy receipt and more recent diagnoses (2005-2011 vs. 1995-1999; OR 1.60, 95%CI 1.14, 2.25), poorly versus well-differentiated tumors (OR 1.69, 95%CI 1.16, 2.46) and endocrine therapy (OR 3.37, 95%CI 2.56, 4.44). CONCLUSIONS: Clinical characteristics were the strongest determinants of DCIS radiotherapy. Receipt was largely unrelated to lifestyle factors suggesting that the previously observed associations in SEER were likely not confounded by these lifestyle factors. Further studies are needed to understand mechanisms driving radiotherapy-associated second malignancies following DCIS, to identify prevention opportunities for this growing population.

Racial and ethnic differences in risk of second primary cancers among prostate cancer survivors.

PURPOSE: Previous studies have shown an overall decreased risk of second cancers among prostate cancer survivors, but this has not been comprehensively examined by race/ethnicity. We conducted a retrospective cohort study of 716,319 one-year survivors of prostate cancer diagnosed at ages 35-84 during 2000-2015 as reported to 17 US Surveillance, Epidemiology and End Results (SEER) registries. METHODS: We estimated standardized incidence ratios (SIRs) for second primary non-prostate malignancies by race/ethnicity (non-Latino white, Black, Asian/Pacific Islander [API] and Latino), by Gleason, and by time since prostate cancer diagnosis. Poisson regression models were used to test heterogeneity between groups with the expected number as the offset. RESULTS: 60,707 second primary malignancies were observed. SIRs for all second cancers combined varied significantly by race/ethnicity: SIRwhite: 0.88 (95% confidence interval: 0.87-0.89), SIRLatino: 0.92 (0.89-0.95), SIRBlack: 0.97 (0.95-0.99), and SIRAPI: 1.05 (1.01-1.09) (p-heterogeneity < 0.001). SIRs for all cancers combined were higher among survivors of higher vs. lower Gleason prostate cancers irrespective of race/ethnicity. We observed significant heterogeneity by race/ethnicity in SIRs for 9 of 14 second cancer types investigated including lung, bladder, kidney, and liver. CONCLUSIONS: Our results confirm that most prostate cancer survivors have lower risks of second cancers than expected, but the magnitude varied by race/ethnicity. Exceptionally, API men had small but significantly increased risk. Further research to understand drivers of the observed race/ethnicity heterogeneity is warranted.

Increasing risk of uterine cervical cancer among young Japanese women: Comparison of incidence trends in Japan, South Korea and Japanese-Americans between 1985 and 2012.

In Japan, cervical cancer incidence has increased since the late 1990s especially among young women, despite a decreasing trend in most developed countries. Here, we examined age, period and birth cohort trends in cervical cancer incidence rates from 1985 to 2012. Incidence rates were ascertained using three population-based cancer registries and analyzed using Joinpoint regression and age-period-cohort models. We compared the findings in Japan to trends among Japanese-Americans in the Surveillance, Epidemiology, and End Results Registries and among women in South Korea using the Korea Central Registry. Age-standardized incidence rates in Japan decreased by 1.7% per year (95% confidence interval - 3.3%, 0.0%) until 1997 and thereafter increased by 2.6% per year (1.1%, 4.2%). Incidence rates increased among women under age 50, were stable among women aged 50-54, and decreased or remained stable among women aged 55 and over. The age-standardized incidence rate ratio by birth cohort showed a U-shaped pattern with the lowest rates in women born in the late 1930s and 1940s. In comparison, women born before 1920 and after 1970 had about double the incidence. Increasing risk in recent birth cohorts was not evident in Japanese-American or South Korean women. The trends in Japan may be attributable to increasing prevalence of human papillomavirus (HPV) infection among young women. Screening and vaccination have been shown to be highly effective and would help reverse these trends.

Trends in pediatric thyroid cancer incidence in the United States, 1998-2013.

BACKGROUND: Pediatric differentiated thyroid cancer (DTC) rates have increased over time in the United States and worldwide. Improvements in imaging for the diagnosis of DTC have been hypothesized as a potential driver of these increases. This study stratifies temporal trends in pediatric DTC by stage and tumor size to assess whether rates of large, late-stage cancers, which are likely to be clinically meaningful, are increasing over time. METHODS: Age-standardized incidence rates (ASRs) of DTC and annual percent changes (APCs) in primary DTC rates were estimated for 0- to 19-year-olds with data from 39 US cancer registries during 1998-2013. RESULTS: During 1998-2013, 7296 cases of DTC were diagnosed (6652 papillary cases and 644 follicular cases). APCs of pediatric DTCs significantly increased by 4.43%/y [95% CI, 3.74%/y-5.13%/y], primarily because of increases in papillary histologies. Increasing trends were observed for children aged 10 to 19 years for both sexes and for non-Hispanic whites, non-Hispanic blacks, and Hispanics. Rates increased significantly over the time period for all tumor stages (APClocalized , +4.06%/y [95% CI, 2.84%/y-5.29%/y]; APCregional , +5.68%/y [95% CI, 4.64%/y-6.73%/y]; APCdistant , +8.55%/y [95% CI, 5.03%/y-12.19%/y]) and across tumor sizes (APC<1 cm , +9.46%/y [95% CI, 6.13%/y-12.90%/y]; APC1-2 cm , +6.92%/y [95% CI, 4.31%/y-9.60%/y]; APC>2 cm , +4.69%/y [95% CI, 2.75%/y-6.67%/y]). CONCLUSIONS: Significantly increasing rates of DTC over time among 10- to 19-year-olds in the United States are unlikely to be entirely explained by increases in medical surveillance during childhood because rates of large and late-stage DTC are increasing over time. Future studies should examine environmental and other factors that may be contributing to rising DTC rates.

Cancer incidence and survival among Métis adults in Canada: results from the Canadian census follow-up cohort (1992-2009).

BACKGROUND: Métis people are 1 of 3 Aboriginal groups recognized by the Canadian constitution. We estimated site-specific incidence rates and survival for the most common cancers among Métis adults in Canada and compared these with rates among non-Aboriginal adults in Canada. METHODS: We examined responses to the 1991 long-form census, including self-reported Métis ancestry linked to national mortality and cancer databases for followup from 1992 to 2009. We estimated age-standardized incidence rates and 5-year relative survival. We determined relative risk (RR) of cancer among Métis and non-Aboriginal adults using Poisson regression, and estimated excess mortality rate ratios using ethnicity-specific life tables. RESULTS: For all cancers and both sexes combined, cancer incidence was similar for Métis and non-Aboriginal adults. However, incidence was significantly higher among Métis adults than among non-Aboriginal adults for the following cancers: female breast (RR 1.18, 95% confidence interval [CI] 1.02-1.37), lung (RR 1.34, 95% CI 1.18-1.52), liver (RR 2.09, 95% CI 1.30-3.38), larynx (RR 1.60, 95% CI 1.03-2.48), gallbladder (RR 2.35, 95% CI 1.12-4.96) and cervix (RR 1.84, 95% CI 1.23-2.76). Métis people had poorer survival for prostate cancer (excess mortality rate ratio 2.60, 95% CI 1.52-4.46). INTERPRETATION: We found higher incidence for several cancers and poorer survival after prostate cancer among Métis adults. Several of these disparities may be related to lifestyle factors (including tobacco use, obesity and lack of cancer screening), providing evidence to support development of public health policy and health care to address cancer burden in the Métis people of Canada.

Radiotherapy for ductal carcinoma in situ and risk of second non-breast cancers.

PURPOSE: Radiotherapy for ductal carcinoma (DCIS) is increasing, but the risks and benefits of the treatment remain uncertain. We aimed to investigate the relationship between radiotherapy for DCIS and risk of second non-breast cancers in a large US cohort. METHODS: We conducted a retrospective cohort study of 52,556 women in 12 U.S. population-based cancer registries diagnosed with first primary DCIS during 1992-2008 at age 25-79 years. We estimated relative risks (RRs), attributable risks (AR), and excess absolute risks (EAR) of second non-breast cancers associated with radiotherapy using Poisson regression adjusted for age at year of diagnosis, grade, hormonal therapy (yes/no or unknown), and time since diagnosis. RESULTS: Approximately half of the women (46.3%) received radiotherapy. Radiotherapy was associated with an increased risk of all second non-breast cancers combined [RR 1.17, 95% confidence interval (CI) 1.08-1.28] and all in-field, radiation-related second cancers combined (RR 1.37, 95% CI 1.15-1.63), driven by second lung cancers (RR 1.33, 95% CI 1.10-1.60) and non-CLL leukemia (RR 1.71, 95% CI 1.02-2.86). The estimated cumulative excess risk of all second non-breast cancers was 0.8% by 15 years after DCIS diagnosis. CONCLUSIONS: Radiotherapy was associated with an increased risk of second non-breast cancers. The specific excess of cancers at sites likely in/near the radiotherapy field suggests the findings are unlikely due exclusively to confounding, but further research into factors related to receipt of radiotherapy is needed. Our risk estimates can be used to help assess the balance of the risks and benefits of radiotherapy for DCIS and to inform clinical practice.

Choice of relative or cause-specific approach to cancer survival analysis impacts estimates differentially by cancer type, population, and application: evidence from a Canadian population-based cohort study.

BACKGROUND: Cause-specific (CS) and net survival in a relative survival framework (RS) are two of the most common methods for estimating cancer survival. In this paper, we assess the differences in results produced by two permutations of cause-specific and relative survival applied to estimating cancer survival and disparities in cancer survival, using data from First Nations and non-Aboriginal populations in Canada. METHODS: Subjects were members of the 1991 Canadian Census Mortality Cohort, a population-based cohort of adult respondents to the 1991 Long Form Census who have been followed up for incident cancers and death through linkage to administrative databases. We compared four methods: relative survival analyses with ethnicity-specific life tables (RS-ELT); relative survival with general population life tables (RS-GLT); cause-specific survival with a broad definition of cancer death (CS-Broad); and cause-specific survival with a narrow definition of cause of death (CS-Narrow) and applied these to the nine most common cancers among First Nations. RESULTS: Apart from breast and prostate cancers, RS-ELT, RS-GLT, and CS-Broad tended to produce similar estimates of age-standardized five-year survival, whereas CS-Narrow yielded higher estimates of survival. CS-Narrow estimates were particularly unlike those based on the other methods for cancers of the digestive and respiratory tracts. Estimates of disparities in survival were generally comparable across the four methods except for breast and prostate cancers. CONCLUSIONS: Cancer surveillance efforts in sub-populations defined by race, ethnicity, geography, socioeconomic status, or similar factors are necessary for identifying disparities and monitoring progress toward reducing them. In the absence of routine monitoring of cancer survival and cancer survival disparities in these populations, estimates generated by different methods will inevitably be compared over time and across populations. In this study, we demonstrate that caution should be exercised in making these comparisons, particularly in interpreting cause-specific survival rates with an unknown or narrow definition of cancer death and in estimates of breast and prostate cancer survival and/or disparities in survival generated by different methods.

Cancer survival among First Nations people of Ontario, Canada (1968-2007).

We aimed to compare cancer survival in Ontario First Nations people to that in other Ontarians for five major cancer types: colorectal, lung, cervix, breast and prostate. A list of registered or "Status" Indians in Ontario was used to create a cohort of over 140,000 Ontario First Nations people. Cancers diagnosed in cohort members between 1968 and 2001 were identified from the Ontario Cancer Registry, with follow-up for death until December 31st, 2007. Flexible parametric modeling of the hazard function was used to compare the survival experience of the cohort to that of other Ontarians. We considered changes in survival from the first half of the time period (1968-1991) to the second half (1992-2001). For other Ontarians, survival had improved over time for every cancer site. For the First Nations cohort, survival improved only for breast and prostate cancers; it either declined or remained unchanged for the other cancers. For cancers diagnosed in 1992 or later, all-cause and cause-specific survival was significantly poorer for First Nations people diagnosed with breast, prostate, cervical, colorectal (male and female) and male lung cancers as compared to their non-First Nations peers. For female lung cancer, First Nations women appeared to have poorer survival; however, the result was not statistically significant. Ontario's First Nations population experiences poorer cancer survival when compared to other Ontarians and strategies to reduce these inequalities must be developed and implemented.

Cancer Incidence by Race and Immigration Status in Canada: Value of Enhanced Sociodemographic Data for Disease Surveillance.

Metrics of cancer burden stratified by race can inform tailored prevention strategies. Examining how these metrics, such as incidence, vary by immigration status can provide insight into the drivers of differential cancer risk by race. The conduct of such analyses in Canada has historically been hindered by a lack of sociodemographic data in routine health data sources, including cancer registries. In their recent study, Malagón and colleagues overcome this challenge by using National Cancer Registry data linked to self-reported race and place of birth from the Canadian census. The study provides estimates of cancer incidence for 19 cancer sites across more than 10 racial groups. Compared with the total population, they found that cancer risk tended to be lower among persons belonging to non-White, non-Indigenous racial groups. Exceptions were stomach, liver, and thyroid cancers where incidence rates were higher in minority groups than in the White population. For some cancers and racial groups, incidence was lower irrespective of immigration status, suggesting the healthy immigrant effect may be sustained across generations or that other factors are also at play. The results highlight potential areas for deeper inquiry and underscore the value of sociodemographic data for disease surveillance. See related article by Malagón et al., p. 906.

Age-related differences in colon and rectal cancer survival by stage, histology, and tumour site: An analysis of United States SEER-18 data.

Age-related differences in colon and rectal cancer survival have been observed, even after accounting for differences in background mortality. To determine how stage, tumour site, and histology contribute to these differences, we extracted age-specific one-year relative survival ratio (RS) stratified by these factors. We used colon and rectal cancer cases diagnosed between 2012 and 2016 from 18 United States Surveillance Epidemiology and End Results cancer registries. For colon cancer, 1-year RS ranged from 87.8 % [95 % Confidence Interval: 87.5-88.2] in the 50-64-year-olds to 62.3 % [61.3-63.3] in 85-99-year-olds and for rectal cancer ranged from 92.3 % [91.8-92.7] to 65.0 % [62.3-67.5]. With respect to stage, absolute differences in RS between 50-64-year-olds and 75-84-year-olds increased with increasing stage (from 6 [5-7] %-points in localised disease to 27 [25-29] %-points in distant disease) and were the highest for cancers of unknown stage (> 28 %-points). Age-related differences in survival were smallest for persons with tumours in the right-sided colon (8 [7-9] %-points) and largest for tumours of the colon without tumour site further specified (25 [21-29] %-points). With respect to histology, differences ranged from 7.4 % to 10.6 %-points for cancers with one of the three primary histologies (adenocarcinoma, mucinous adenocarcinoma, signet ring cell carcinoma) and were several-fold higher (42 %-points) for those with unknown/other histology (< 6 % of cases). Because age-related differences in survival were observed for all histologies and tumour sites, RS differences are unlikely to be driven by differences in the distribution of these factors by age. Differences in stage distribution by age are likely to contribute toward age-related differences in survival. Within stage groups, age differences in survival could be explained by frailty and/or therapy. Future studies incorporating data on treatment and geriatric conditions including frailty and comorbidity would support further understanding of the age gap in colon and rectal cancer survival.

Temporal trends in the incidence of malignant and nonmalignant primary brain and central nervous system tumors by the method of diagnosis in England, 1993-2017.

BACKGROUND: Several studies report increases in the incidences of primary central nervous system (CNS) tumors. The reasons for this are unclear. METHODS: Data on all 188 340 individuals diagnosed with a primary CNS tumor in England (1993-2017) were obtained from the National Cancer Registration and Analysis Service. Data on all computerized tomography (CT) head and magnetic resonance imaging (MRI) brain scans in England (2013-2017) were obtained from the National Health Service Digital. Age-sex-standardized annual incidence rates per 100 000 population (ASR) were calculated by calendar year, tumor behavior, tumor location, and method of diagnosis. Temporal trends were quantified using average annual percent change (AAPC). RESULTS: The ASR for all CNS tumors increased from 13.0 in 1993 to 18.6 in 2017 (AAPC: +1.5%, 95% CI: 1.3, 1.7). The ASR for malignant tumors (52% overall) remained stable (AAPC: +0.5%, 95% CI: -0.2, 1.3), while benign tumors (37% overall) increased (AAPC: +2.6%, 95% CI: 1.2, 4.0). Among the 66% of benign tumors that were microscopically confirmed, the ASR increased modestly (AAPC: +1.3%, 95% CI: 0.5, 2.1). However, among the 25% of benign tumors that were radiographically confirmed, the ASR increased substantially (AAPC: 10.2%, 95% CI: 7.9, 12.5), principally driven by large increases in those who are aged 65+ years. The rate of CT head scans in Accident & Emergency (A&E) increased during 2013-2017, with especially large increases in 65-84 and 85+-year-olds (AAPCs: +18.4% and +22.5%). CONCLUSIONS: Increases in CNS tumor incidence in England are largely attributable to the greater detection of benign tumors. This could be the result of the increasing use of neuroimaging, particularly CT head scans in A&E in people who are aged 65+ years.

Trends in diagnostic tests ordered for children: a retrospective analysis of 1.7 million laboratory test requests in Oxfordshire, UK from 2005 to 2019.

OBJECTIVE: To better understand testing patterns in children, we measured temporal trends in paediatric testing from 2005 to 2019 in Oxfordshire, UK. DESIGN: Descriptive study of population-based secondary data. SETTING: Oxfordshire University Hospitals National Health Service Trust laboratories. PARTICIPANTS: Children aged 0-15 years in Oxfordshire who received at least one blood test. MAIN OUTCOME MEASURES: We estimated average annual percentage changes (AAPCs) in test use using joinpoint regression models. Temporal changes in age-adjusted rates in test use were calculated overall and stratified by healthcare setting, sex, and age. RESULTS: Between 2005 and 2019, 1 749 425 tests were performed among 113 607 children. Overall test use declined until 2012, when test rates appeared to increase (AAPC 1.5%, 95% CI -0.8% to 3.9%). Most tests were performed in inpatient settings, where testing rates stayed steady (AAPC -0.6%, 95% CI -2.1% to 0.9%). Increases were highest in females, those aged 6-15 years and in the outpatient setting. The greatest increase in testing was for vitamin D (AAPC 26.5%), followed by parathyroid hormone (9.8%), iron studies (9.3%), folate (8.4%), vitamin B12 (8.4%), HbA1c (8.0%), IgA (7.9%) and coeliac (7.7%). CONCLUSIONS: After an initial decline, laboratory test use by children in Oxfordshire demonstrated an apparent increase since 2012. Test use increased in outpatient and general practice settings, however remained steady in inpatient settings. Further research should examine the root causes and implications for test increases, and whether these increases are warranted. We encourage clinicians to consider the individual and systemic implications of performing blood tests in children.

Comparing Risk for Second Primary Cancers After Intensity-Modulated vs 3-Dimensional Conformal Radiation Therapy for Prostate Cancer, 2002-2015.

Importance: Compared with 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiotherapy (IMRT) can spare nearby tissue but may result in increased scatter radiation to distant normal tissue, including red bone marrow. It is unclear whether second primary cancer risk varies by radiotherapy type. Objective: To evaluate whether radiotherapy type (IMRT vs 3DCRT) is associated with second primary cancer risk among older men treated for prostate cancer. Design, Setting, and Participants: In this retrospective cohort study of a linked database of Medicare claims and Surveillance, Epidemiology, and End Results (SEER) Program population-based cancer registries (2002-2015), male patients aged 66 to 84 diagnosed with a first primary nonmetastatic prostate cancer from 2002 to 2013, as reported to SEER, and who received radiotherapy (IMRT and/or 3DCRT without proton therapy) within the first year following prostate cancer were identified. The data were analyzed from January 2022 through June 2022. Exposure: Receipt of IMRT and 3DCRT, based on Medicare claims. Main Outcomes and Measures: The association between radiotherapy type and development of a subsequent hematologic cancer at least 2 years after prostate cancer diagnosis or a subsequent solid cancer at least 5 years after prostate cancer diagnosis. Hazard ratios (HRs) and 95% CIs were estimated using multivariable Cox proportional regression. Results: The study included 65 235 2-year first primary prostate cancer survivors (median [range] age, 72 [66-82] years; 82.2% White patients) and 45 811 5-year survivors with similar demographic characteristics (median [range] age, 72 [66-79] years; 82.4% White patients). Among 2-year prostate cancer survivors (median [range] follow-up, 4.6 [0.003-12.0] years), 1107 second hematologic cancers were diagnosed (IMRT, 603; 3DCRT, 504). Radiotherapy type was not associated with second hematologic cancers overall or any specific types evaluated. Among 5-year survivors (median [range] follow-up, 3.1 [0.003-9.0] years), 2688 men were diagnosed with a second primary solid cancer (IMRT, 1306; 3DCRT, 1382). The overall HR for IMRT vs 3DCRT was 0.91 (95% CI, 0.83-0.99). This inverse association was restricted to the earlier calendar year period of prostate cancer diagnosis (HR2002-2005 = 0.85; 95% CI, 0.76-0.94; HR2006-2010 = 1.14; 95% CI, 0.96-1.36), with a similar pattern observed for colon cancer (HR2002-2005 = 0.66; 95% CI, 0.46-0.94; HR2006-2010 = 1.06; 95% CI, 0.59-1.88). Conclusions and Relevance: The results of this large, population-based cohort study suggest that IMRT for prostate cancer is not associated with an increased risk of second primary cancers, either solid or hematologic, and any inverse associations may be associated with calendar year of treatment.

Serious disease risk among patients with unexpected weight loss: a matched cohort of over 70 000 primary care presentations.

BACKGROUND: Unexpected weight loss (UWL) in patients consulting in primary care presents dilemmas for management because of the broad differential diagnoses associated with UWL. Research on the risks of serious disease among patients with UWL to date has largely taken place in secondary care, limiting generalizability to primary care patients. In this study, we use a large matched cohort study to estimate the risks of 12 serious diseases among patients presenting to primary care with UWL where this was recorded, stratified by age and sex, in order to inform a rational clinical approach to patients presenting with UWL. METHODS: This was a retrospective matched cohort study using electronic health records (EHRs) from the UK Clinical Practice Research Datalink (CPRD). Each patient with UWL (ascertained from EHR coding) was matched to five patients without UWL and followed until the earliest of a diagnosis of the serious disease, date of death, exit from the CPRD database, or end of the study. Observed absolute risks of the 12 serious diseases were estimated as probabilities, and hazard ratios (HRs) were estimated with Cox proportional hazards models. RESULTS: Between 2000 and 2012, 70 193 patients in CPRD had at least one record of UWL and were matched with 295 579 patients without UWL. Patients with UWL had significantly higher risk of nearly all serious diseases examined compared with patients without. HRs ranged from 1.43 for congestive heart failure [95% confidence interval (CI): 1.27-1.62] to 9.70 for malabsorption (95% CI: 6.81-13.82). The absolute risks of any given serious disease were relatively low (<6% after 1 year). The magnitude and rank order of absolute risks varied by age and sex. Depression was the most common diagnosis among women aged <80 with UWL (3.74% of women aged <60 and 2.46% of women aged 60-79), whereas diabetes was the most common in men <60 with UWL (2.96%) and cancer was the most common in men aged 60 and over with UWL (3.79% of men aged 60-70 and 5.28% of men aged ≥80). CONCLUSIONS: This analysis provides new evidence to patients and clinicians about the risks of serious disease among patients presenting with UWL in primary care. Depending on age and sex, the results suggest that workup for UWL should include screening for diabetes, thyroid dysfunction, depression, and dementia. If performed in a timely manner, this workup could be used to triage patients eligible for cancer pathway referral.

Pooled Analysis of Meningioma Risk Following Treatment for Childhood Cancer.

Importance: Meningioma is the most common subsequent neoplasm following cranial irradiation among survivors of childhood cancer, but there are still uncertainties regarding the magnitude of the radiation dose-response association, potential modifiers of radiation risks, and the role of chemotherapy. Objective: To evaluate meningioma risk in survivors of childhood cancer following radiotherapy and chemotherapy and identify possible modifying factors of radiation-associated risk. Design, Setting, and Participants: This international case-control study pooled data from 4 nested case-control studies of survivors of childhood cancer diagnosed between 1942 and 2000, followed through 2016. Cases were defined as participants diagnosed with a subsequent meningioma. Controls were matched to cases based on sex, age at first cancer diagnosis, and duration of follow-up. Data were analyzed from July 2019 to June 2022. Exposures: Radiation dose (Gy) to the meningioma site and cumulative chemotherapy doses, including intrathecal and systemic methotrexate doses. Main Outcomes and Measures: The main outcome was subsequent meningioma, assessed using odds ratios (ORs) and excess odds ratios per gray (EOR/Gy). Results: The analysis included 273 survivors of childhood cancer who developed meningioma (cases) and 738 survivors who did not (controls), with a total of 1011 individuals (median [IQR] age at first cancer diagnosis 5.0 [3.0-9.2] years; 599 [59.2%] female). Median (IQR) time since first cancer was 21.5 (15.0-27.0) years. Increasing radiation dose was associated with increased risk of meningioma (EOR/Gy, 1.44; 95% CI, 0.62-3.61), and there was no evidence of departure from linearity (P = .90). Compared with survivors who were not exposed to radiation therapy, those who received doses of 24 Gy or more had more than 30-fold higher odds of meningioma (OR, 33.66; 95% CI, 14.10-80.31). The radiation dose-response association was significantly lower among patients treated at age 10 years or older compared with those treated before age 10 years (EOR/Gy, 0.57; 95% CI, 0.18-1.91 vs 2.20; 95% CI, 0.87-6.31; P for heterogeneity = .03). Risk associated with radiation remained significantly elevated 30 years after exposure (EOR/Gy, 3.76; 95% CI, 0.77-29.15). We found an increased risk of meningioma among children who had received methotrexate (OR, 3.43; 95% CI, 1.56-7.57), but no evidence of a dose-response association or interaction with radiation dose. Conclusions and Relevance: These findings suggest that the meninges are highly radiosensitive, especially for children treated before age 10 years. These results support the reduction in whole-brain irradiation over recent decades and the prioritization of approaches that limit radiation exposure in healthy tissue for children. The persistence of elevated risks of meningiomas for 30 years after cranial radiotherapy could help inform surveillance guidelines.