Incidence Rates Of Second Cancers Research Articles

Nonsteroidal Anti-Inflammatory Drugs Reduce Second Cancer Risk in Patients With Breast Cancer: A Nationwide Population-Based Propensity Score-Matched Cohort Study in Taiwan.

Nonsteroidal anti-inflammatory drugs (NSAIDs) reduce mortality in patients with cancer, especially breast cancer, but their influence on second cancer risk is uncertain. This study aimed to examine whether NSAID use is associated with second cancer risk in patients with breast cancer. This population-based propensity score-matched cohort study using Taiwan’s National Health Insurance Research Database enrolled patients with newly diagnosed breast cancer (n = 7356) with and without (n = 1839) NSAID therapy from 2000 to 2009. They were followed up until the diagnosis of second cancer, death, or end of 2011. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHR). The NSAID cohort had a lower incidence rate of second cancer than the non-NSAID cohort (5.57 vs. 9.19 per 1,000 person-years), with an aHR of 0.63 (95% confidence interval (CI) 0.46–0.87). When compared with the non-NSAID cohort, the second cancer incidence was lower in patients taking non-cyclooxygenase 2 inhibitors (aHR 0.67, 95% CI 0.47–0.94) and in those receiving multiple NSAIDs during follow-up (aHR 0.55, 95% CI 0.37–0.84). A dose–response relationship existed in NSAID cumulative days. The findings demonstrate that NSAID use reduces second cancer risk in a dose-dependent manner in patients with primary breast cancer.

Second Cancers in Adults with Acute Promyelocytic Leukemia (APL) Treated with or without Arsenic Trioxide (ATO): A SEER-Medicare Analysis

Background: ATO was approved by the U.S. Food and Drug Administration in 2000 for treatment of patients with relapsed/refractory APL and in 2018 in combination with all-trans retinoic acid (ATRA) for adults with newly-diagnosed low-risk APL. ATRA and ATO combinations result in long-term remissions in most patients with APL (Lo-Coco et al. NEJM 2013, Burnett et al. Lancet Oncol 2015). However, epidemiologic studies have shown associations between exposure to inorganic arsenic and development of skin, lung, bladder, and potentially liver, kidney, and prostate cancers (IARC 2004). The prescribing information for ATO includes a warning for carcinogenesis, with advice to monitor patients for development of second primary malignancies. Retrospective cohort analyses of second cancers in APL patients treated with ATO have been performed, finding incidence rates of 1-5% (Eghtedar et al. Leuk Lymphoma 2015, Au et al. Leuk Res 2007, Zhu et al. Blood 2016). We sought to perform an exploratory population-based analysis of second cancers in adults with APL treated with ATO compared to those treated with other systemic APL therapies without ATO using the linked Surveillance, Epidemiology, and End Results (SEER)-Medicare database. Methods: Using SEER-Medicare linked data, we identified APL patients diagnosed from January 1, 2006 to December 31, 2015. Patients whose first SEER cancer diagnosis was APL, who were continuously enrolled in Medicare Parts A, B, & D from the month of their APL diagnosis, and who received treatment with ≥ 1 systemic APL therapy within 1 year of diagnosis were included. Patients were followed from their first month of treatment group-defining APL therapy (ATO or non-ATO containing) until disenrollment from Medicare Parts A, B, or D, end of study period, or death. We determined the cumulative incidence of SEER-confirmed second cancers and overall survival (OS) according to whether patients were treated with or without ATO using the Kaplan-Meier method. We used a multivariate Cox proportional hazards model to estimate the hazard ratios (HR) and 95% confidence intervals (CI) of cumulative incidence of second cancers and OS adjusted for relevant covariates of age, sex, and year of diagnosis. Results: We identified 1,442 APL cases, with 1,179 having APL as their first cancer diagnosis, of which 246 were enrolled in Medicare Parts A, B, and D. Of these, 64 received ATO and 60 received systemic APL therapy without ATO within 1 year of diagnosis. Characteristics, follow-up, and second malignancies for these cohorts are presented in the Table. Absolute incidence rates of second cancer were 3.4 per 1000 person-months compared to 1.4 per 1000 person-months in patients treated with and without ATO, respectively, and cumulative incidence rates at 24 months were 9.9% and 6.0%, respectively (p=0.20) (Figure 1). Mortality rates were 1.9 per 1000 person-months compared to 5.1 per 1000 person-months in patients treated with and without ATO, respectively, and OS rates at 24 months were 90.8% and 81.5%, respectively (p=0.10) (Figure 2). After adjusting for relevant covariates, HR for cumulative incidence of second malignancies in patients treated with ATO was 1.27 (95% CI 0.29-5.49; p=0.75) and for OS was 0.46 (95% CI 0.16-1.29; p=0.14) compared to APL therapy without ATO. Conclusions: This exploratory analysis revealed a high incidence of second malignancies in APL patients treated with ATO, although the risk was not significantly increased compared to patients who received other APL therapies. Most second malignancies following ATO were solid tumors, in line with prior epidemiologic studies of inorganic arsenic exposures. Despite the occurrence of second malignancies, there was a tendency towards longer OS in patients treated with ATO. Given the small sample size, short follow-up, potential selection and immortal time bias, and unaccounted for differences between comparator groups, firm conclusions cannot be inferred. However, the nearly 10% cumulative incidence of second malignancies at 24 months follow-up in Medicare patients with APL treated with ATO suggests the need for close monitoring for second malignancies following ATO therapy. Further prospective research into second malignancies following ATO is needed. Disclosures No relevant conflicts of interest to declare.

The ANDANTE project: a multidisciplinary approach to neutron RBE.

The usual method for estimating the risk from exposure to neutrons uses the concept of relative biological effectiveness (RBE) compared with the risk from photons, which is better known. RBE has been evaluated using cellular and animal models. But this causes difficulties in applying the concept to humans. The ANDANTE project takes a new approach using three different disciplines in parallel: Physics: a track structure model is used to contrast the patterns of damage to cellular macro-molecules from neutrons compared with photons. The simulations reproduce the same energy spectra as are used in the other two approaches. Stem cell radiobiology: stem cells from thyroid, salivary gland and breast tissue are given well characterised exposures to neutrons and photons. A number of endpoints are used to estimate the relative risk of damage from neutrons compared with photons. Irradiated cells will also be transplanted into mice to investigate the progression of the initial radiation effects in stem cells into tumours in a physiological environment. the relative incidence rates of second cancers of the thyroid, salivary gland and breast following paediatric radiotherapy (conventional radiotherapy for photons and proton therapy for neutrons) are investigated in a pilot single-institution study, exploring the possible design of a multi-institution prospective study comparing the long-term out-of-field and in-field effects of scanned and scattered protons. The results will be used to validate an RBE-based risk model developed by the project, and validate the corresponding RBE values.

Second cancer after radiotherapy, 1981–2007

Background and purposeToday, there is growing concern about radiotherapy induced secondary malignancies. We analysed the incidence and dose dependence of second cancer. Material and methodsThe study includes 12,000 one-year survivors of radiotherapy, treated between 1981 and 2007. For risk estimates a public databank on cancer in Germany served as reference. Contralateral second breast cancer, second oesophageal and colorectal cancer were analysed with retrospective dosimetry. GI-tract data were used for risk modelling. ResultsThe incidence rate of second cancers (493 cases) was ∼1% per year. Contralateral breast cancer was the most frequent entity (relative risk RR=2.8). The scatter-dose gradient (2–3Gy) across the contralateral breast did not cause a detectable risk gradient. There was an increased risk for second head and neck cancer (RR=5.1) and for male oesophageal cancer (RR=5.8). For both entities, dose response modelling with case-control data predicted maximum curves with peak induction at 1–5Gy and positive excess absolute risk values at high doses. ConclusionsA survey of second cancer after radiotherapy requires follow-up over decades. Preliminary dose response modelling albeit with low case numbers suggests an increased risk from multiportal techniques. To improve risk assessment, prospective out-of-field dosimetry and long-term multicentre data collection are recommended.

Incidence of second malignancies among 10,919 patients over 20 years: Retrospective analysis of a community hospital cancer registry data.

e12026 Background: Diagnosis of a second cancer contributes significantly to subsequent morbidity and mortality in cancer survivors. The aim of this study is to ascertain the incidence and characteristics of second cancers among adult patients enrolled in the Hurley Medical Center cancer registry. Methods: The registry was searched for patients enrolled during 1988-2007, who were diagnosed with subsequent cancers. Incidence and survival was analysed. Results: Total follow up was for over 78,680 person-years. 700 patients (6.4%) had subsequent cancers over 20 years, compared to SEER results of 13.7% over 20 years. Further analyses were performed on 534 patients (76%) for whom detailed data was available. Incidence rate of second cancers was 0.6% per year of follow up. About 25 second cancers were diagnosed annually, making up 5% of the ∼550 new diagnoses, compared to 16% in SEER data. Median interval between the diagnoses of the two cancers was 32 months. Among second cancer sites, breast (20%), lung (17%) head and neck (7.5%), colorectal (7.1%) and prostate (6.9%) were most frequent. In comparison, commonest second sites described in the SEER report are: lung (17.3%), breast (16.4%), colon (11.1%), prostate (10%) and head and neck (4.8%). 242 (45.3%) of the patients were male, and 292 (54.7%) were female. Mean age at diagnosis of the first cancer was 62 years and second cancer was 65 years. Median survival duration was 82 months after first cancer and 33 months after the second. After a median of 10 years of follow up, 192 (36%) were alive. In the SEER analysis, 20% survived to 10 years. Analysis of causes of death showed that 41 were directly and 9 were indirectly related to the cancer. This information was unavailable for 258 patients (75%). Conclusions: Compared to SEER data, recorded incidences of second cancers are lower in our cancer registry, and survival proportion at 10 years is higher. Incomplete follow up due to out-migration of patients may have contributed to low incidence. Second cancers may be related to common risk factors and some are detectable by age-appropriate screening programs. Hence it is important to emphasize lifestyle modifications and cancer surveillance among cancer survivors. No significant financial relationships to disclose.

Late Effects after Autologous Hematopoietic Cell Transplantation

Over 30,000 autologous hematopoietic cell transplants (HCT) have been performed yearly during the past decade. With improvement in supportive care, few patients succumb to early treatment complications; hence, more attention is being paid to causes of late complications and death. However, interpretation of the data that exist is difficult as the definition of ‘‘late’’ varies by study, as does the patient population, underlying diseases, HCT mobilization and conditioning regimens, stem cell sources, and duration of follow-up (Table 1). Most importantly, the methods used to estimate the incidence of late complications over time are different or are not explained in sufficient detail. Some studies report relative risk or standardized mortality compared with the general population. Other studies report an acturial estimate (which ignores competing risks and thus may overestimate the incidence), whereas others report cumulative incidence calculations.