Subsequent Primary Malignancies Research Articles

Risk of developing glioblastoma following non-CNS primary cancer: a SEER analysis between 2000 and 2018.

Patients with a prior malignancy are at elevated risk of developing subsequent primary malignancies (SPMs). However, the risk of developing subsequent primary glioblastoma (SPGBM) in patients with a prior cancer history is poorly understood. We used the Surveillance, Epidemiology, and End Results (SEER) database and identified patients diagnosed with non-CNS malignancy between 2000 and 2018. We calculated a modified standardized incidence ratio (M-SIR), defined as the ratio of the incidence of SPGBM among patients with initial non-CNS malignancy to the incidence of GBM in the general population, stratified by sex latency, and initial tumor location. Of the 5,326,172 patients diagnosed with a primary non-CNS malignancy, 3559 patients developed SPGBM (0.07%). Among patients with SPGBM, 2312 (65.0%) were men, compared to 2,706,933 (50.8%) men in the total primary non-CNS malignancy cohort. The median age at diagnosis of SPGBM was 65years. The mean latency between a prior non-CNS malignancy and developing a SPGBM was 67.3months (interquartile range [IQR] 27-100). Overall, patients with a primary non-CNS malignancy had a significantly elevated M-SIR (1.13, 95% CI 1.09-1.16), with a 13% increased incidence of SPGBM when compared to the incidence of developing GBM in the age-matched general population. When stratified by non-CNS tumor location, patients diagnosed with primary melanoma, lymphoma, prostate, breast, renal, or endocrine malignancies had a higher M-SIR (M-SIR ranges: 1.09-2.15). Patients with lung cancers (M-SIR 0.82, 95% CI 0.68-0.99), or stomach cancers (M-SIR 0.47, 95% CI 0.24-0.82) demonstrated a lower M-SIR. Patients with a history of prior non-CNS malignancy are at an overall increased risk of developing SPGBM relative to the incidence of developing GBM in the general population. However, the incidence of SPGBM after prior non-CNS malignancy varies by primary tumor location, with some non-CNS malignancies demonstrating either increased or decreased predisposition for SPGBM depending on tumor origin. These findings merit future investigation into whether these relationships represent treatment effects or a previously unknown shared predisposition for glioblastoma and non-CNS malignancy.

Multiple primary malignancies in 788 Chinese patients with diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most common histological subtype of non-Hodgkin lymphoma worldwide. The emergence of multiple primary malignancies (MPMs) has been described as a new prognostic factor in many types of tumors. To investigate the morbidity, incidence, and survival of MPM in DLBCL, we retrospectively reviewed the characteristics of 788 patients with DLBCL. Forty-two patients were diagnosed with MPM, and 22 of them were diagnosed with subsequent primary malignancies (SPM) by pathologic biopsy. The incidence of SPM was associated with older age. Germinal center B-cell-like (GCB) subtype and earlier Ann Arbor stage DLBCL patients were more prone to SPM. MPM, age, lactate dehydrogenase (LDH) level, Eastern Cooperative Oncology Group performance status (ECOG PS), Hans classification, and international prognostic index (IPI) score were prognostic risk factors for overall survival (OS). These data provide a comprehensive view of MPM in DLBCL. MPM was an independent prognostic factor of DLBCL in univariate analysis.

High rate of epidermal growth factor receptor-mutated primary lung cancer in patients with primary breast cancer.

BackgroundWith increased survival in breast cancer, resulting from advances in treatment, patients incur the possibility of subsequent primary malignancies, especially lung cancer. The aim of this study was to assess the frequency of CT-detected pulmonary ground-glass nodules and lung cancer following breast cancer diagnosis, the associations between breast cancer and lung cancer, the pathological features of double primary cancer, and the status of epidermal growth factor receptor (EGFR) mutations in second primary lung cancer.MethodsClinical data from more than 9000 individuals who were diagnosed with primary breast cancer at Jiangsu Province Hospital (Jiangsu, China) between January 2008 and December 2021 were retrospectively analyzed.ResultsOf the 9179 patients, 6512 underwent diagnostic CT, 55 (0.8%) were diagnosed with a second primary lung cancer, which accounted for approximately 18.4% of the pulmonary ground-glass nodules (GGNs) detected. The incidence was higher than in the general female population (standardized incidence ratio 1.4 [95% confidence interval (CI): 1.25-1.55]). Patients who experienced a second primary lung cancer exhibited a significantly higher rate of EGFR mutation (78.5%) than those with lung adenocarcinoma alone, with most exhibiting low-grade malignancy, older age, estrogen receptor negativity, low Ki67, and no lymph node metastasis.ConclusionsBreast cancer patients, especially those with low-grade malignancy, were at high risk for developing primary lung cancer. For isolated GGN in patients with high-risk factors, clinicians should insist on close follow-up. Furthermore, EGFR may play an important role in primary lung adenocarcinomas and breast cancer.

A single centre study from western India to evaluate the frequency of developing second and subsequent multiple primary malignancies among cancer survivors

AimThis study was designed to evaluate the frequency of developing second and subsequent primary cancers among cancer survivors.MethodsWe have retrospectively analyzed 121 multiple primary cancer patients treated at Bhagwan Mahavir Cancer Hospital and Research Centre, Jaipur, Rajasthan, India from the last 20 years. The survival analysis was performed by Kaplan-Meier methodology.ResultsThe prevalence of multiple primary malignant tumors (MPMTs) was 1.51% (121/8000), with a male to female ratio of 1:1.42. In males most of the reported MPMTs were synchronous and most common first primary cancer cases were head & neck and lung whereas, in females most of the reported MPMTs were metachronous and most common first primary cancer cases were breast and gynaecological malignancies. Family history was reported in 15 cases. Maximum 33.05% patients received combined treatment of chemotherapy, radiotherapy and 91.73% (111/121) of patients with MPMTs were effectively followed up, 35 (28.92%) patients died and 5-year survival rate of the remaining 86 patients was 68.46%.ConclusionsIn the present observational study the most frequent sites of MPMTs in men were head & neck and lung whereas, in women breast and gynaecological sites were common. Therefore, careful monitoring and follow up are required for these patients.

649Personal history of keratinocyte carcinoma is a marker of inherited cancer risk: Mendelian randomization analyses

Abstract Background A personal history of keratinocyte carcinoma (KC) has been reported as a risk factor for developing subsequent primary cutaneous and non-cutaneous malignancies. However most evidence to date stems from observational studies which are prone to bias, confounding and reverse causation. Our aim was to examine this association using different Mendelian randomization (MR) approaches. Methods We performed a one-sample MR analysis using individual-level data from the UK Biobank (n = 394,306). This analysis was then validated in an independent dataset in the QSkin cohort (n = 16,896). Using 64 independent genetic variants known to be associated with KC, we generated a polygenic risk score (PRS) for each participant in the UK Biobank and the QSkin cohort. We then performed two-sample MR analyses using genome-wide association study (GWAS) summary statistics. We tested the association between genetically predicted KC and risk of subsequent cancer using logistic regression. Results Results from one-sample MR analyses in the UK Biobank indicated that a personal history of KC was significantly associated with cancer overall (excluding melanoma) (OR: 1.15, 95% CI: 1.10-1.20, per doubling the prevalence of KC). The results from the two-sample MR corroborate the findings from the one-sample MR, although the risk estimate was lower (OR: 1.05, 95% CI: 1.03-1.07). Conclusions Our MR analyses suggest that genetically predicted KC is a risk factor for developing subsequent primary malignancies. Key messages A personal history of KC may serve as a proxy marker of inherited cancer risk.

Changes in Second Primary Malignancies (SPM) after Hodgkin Lymphoma over Time in the United States

Background Improved treatments for Hodgkin lymphoma (HL) have prolonged survival. However, the increased risk of second primary malignancies (SPMs) among HL survivors compared to the general population remains the leading cause of death among long-term HL survivors. Treatment has evolved to include improved radiation techniques and response adapted chemotherapy regimens with the goal of improving HL cure rates, limiting treatment-associated morbidity, and improving long-term overall survival. Few population-based studies in the United States have examined whether the incidence of SPMs has decreased over time with these attempts to limit treatment-related toxicities.Methods Data for 20,530 patients of all ages diagnosed with a first primary HL during 1992-2013 were obtained from 13 Surveillance, Epidemiology and End Results (SEER13) regions in the United States. The incidences of SPM that developed >1 year after the initial HL diagnosis were determined for two treatment eras (1992-2002 and 2003-2013). To balance follow up time, HL patients diagnosed in 1992-2002 were followed through 2002 and patients diagnosed in 2003-2013 were followed through 2013. In each treatment era, we calculated standardized incidence ratios (SIRs) and corresponding 95% confidence intervals (CIs) comparing HL patient's subsequent cancer incidence with the expected number of first primary cancer incidence, based on the age (at 5-year intervals), sex, calendar year (at 5-year intervals), cancer site, and race/ethnicity, derived from the general SEER13 population. SIRs were calculated for all invasive cancers and by cancer categories (solid and hematologic tumors) as well as by HL stage at diagnosis (stage I/II vs stage III/IV) and initial treatment with radiation. The cumulative incidence of SPMs, accounting for the competing risk of death, were estimated, with Gray's K-sample test statistic used to determine whether the difference in cumulative incidence of SPMs by treatment era was statistically significant (P -values that were <0.05).Results The mean follow-up time was 4.9 (±3.3) years for 9,989 patients (n=275 SPMs) diagnosed in 1992-2002 and 4.8 (±3.3) years for 10,541 patients (n=285 SPMs) diagnosed in 2003-2013. The mean age was similar for patients in the two treatment eras (38.4 years, 1992-2002; 39.4 years, 2003-2013). There was a statistically significant increase in SPMs of all sites in both time-periods compared to the expected number of first primary tumors in the general population. More specifically, there was a considerably elevated risk of lymphatic and hematopoietic SPMs amongst all patients with primary HL (1992-2002 SIR: 6.53 (5.24-8.03); 2003-2013 SIR: 5.85 (4.77-7.11)) and a suggestion of elevated risk of solid tumors (1992-2002 SIR: 1.37 (1.17-1.58); 2003-2013 SIR: 1.11 (0.95-1.29)). For all those diagnosed with HL, there was an increased rate of acute myeloid leukemia compared to the general population (1992-2002 SIR: 15.43 (9.14-24.39); 2003-2013 SIR: 17.23 (11.35-25.06)). At 5-years, the cumulative incidence of all SPMs (1992-2002: 1.93%; 2003-2013: 2.12%; p=0.84), lymphatic and hematopoietic SPMs (1992-2002: 1.23%; 2003-2013: 1.25%; p=0.94) and solid SPMs (1992-2002 0.69%, 2003-2013 0.85%, p=0.59) were similar in the two treatment eras (Figure). Further, the cumulative incidence of SPMs did not differ by stage at diagnosis or initial treatment with radiation therapy.Conclusions Despite changes in radiation techniques and chemotherapy regimens for the treatment of HL, there continues to be increased risk of SPMs, specifically those of the lymphatic and hematopoietic systems, in survivors of HL compared to the general population. Additionally, there is no change in the cumulative incidences of SPMs in HL survivors over time. Other studies have shown that SPMs do not begin to peak until 10-15 years after cancer diagnosis. Therefore, it is important to continue to monitor whether changes in treatment regimens will result in fewer SPMs as additional follow-up time becomes available.Figure. Cumulative incidence of all subsequent primary malignancies 1 to 10 years after a first diagnosis of Hodgkin lymphoma, by treatment era. [Display omitted] DisclosuresWun:Janssen: Other: Steering Committee for Cassini Study and Callisto Program, Research Funding; Pfizer: Other: Steering Committee: RESET study, Research Funding.

Radiation-associated breast cancers in a late-effects cohort: Long-term surveillance is essential.

Survivors of childhood, adolescent, and young adulthood malignancies have an increased risk of subsequent primary malignancies, particularly after exposure to therapeutic radiation. This study aims to evaluate the mode of surveillance and surveillance compliance, incidence and mode of detection of breast cancer, breast cancer phenotype, and outcomes after radiation-associated breast cancer (RBC) in a late-effects cohort. Women exposed to therapeutic radiation attending the late effects service from 1st January 2000 to 20th February 2013. All invasive and in-situ cancers, benign tumors, and deaths were evaluated. The incidence of breast cancer was compared to the Australian general population. Compliance with breast surveillance recommendations, clinicopathological features, and management of breast cancers were examined. The prevalence of RBC was 17.1%. Twenty-eight cases of RBC occurred in 24 women, out of 140 women exposed to chest radiation. Patients whose first attendance was ≥15 years after radiation exposure experienced the highest incidence of RBC at 23%. The incidence of breast cancer was 11.2 times the general population (P<.001). Compliance with surveillance mammography was observed in 18.4%. Breast cancers diagnosed after the first attendance to the service were more likely screen-detected (P=.002). Most were hormone receptor positive (84.0%), invasive ductal carcinomas (82.1%), and managed with mastectomy (89.3%). Patients attending a dedicated late effects service have a high burden of subsequent malignancies generally occurring after long latency. Judicious management with adherence to long-term surveillance guidelines is advocated.

NCCN Guidelines Insights: Survivorship, Version 2.2020.

The NCCN Guidelines for Survivorship provide screening, evaluation, and treatment recommendations for consequences of adult-onset cancer and its treatment, with the goal of helping healthcare professionals who work with survivors, including those in primary care. The guidelines also provide recommendations to help clinicians promote physical activity, weight management, and proper immunizations in survivors and facilitate care coordination to ensure that all of the survivors' needs are addressed. These NCCN Guidelines Insights summarize additions and changes made to the guidelines in 2020 regarding cardiovascular disease risk assessment and screening for subsequent primary malignancies.

Colorectal Cancer in the Young: Epidemiology, Prevention, Management

Colorectal cancer (CRC) incidence rates in the United States overall have declined since the mid-1980s because of changing patterns in risk factors (e.g., decreased smoking) and increases in screening. However, this progress is increasingly confined to older adults. CRC occurrence has been on the rise in patients younger than age 50, often referred to as early-onset disease, since the mid-1990s. Young patients are more often diagnosed at an advanced stage and with rectal disease than their older counterparts, and they have numerous other unique challenges across the cancer management continuum. For example, young patients are less likely than older patients to have a usual source of health care; often need a more complex treatment protocol to preserve fertility and sexual function; are at higher risk of long-term and late effects, including subsequent primary malignancies; and more often suffer medical financial hardship. Diagnosis is often delayed because of provider- and patient-related factors, and clinicians must have a high index of suspicion if young patients present with rectal bleeding or changes in bowel habits. Educating primary care providers and the larger population on the increasing incidence and characteristic symptoms is paramount. Morbidity can further be averted by increasing awareness of the criteria for early screening, which include a family history of CRC or polyps and a genetic predisposition.

75P Clinical and pathological feature of primary lung cancer in patients with primary breast cancer

With increased survival in breast cancer, resulting from advances in treatment, patients incur the possibility of subsequent primary malignancies, especially lung cancer. The aim of this study was to assess the frequency of lung cancer following breast cancer diagnosis, the associations between breast cancer and lung cancer, the pathological features of double primary cancer, and the status of epidermal growth factor receptor (EGFR) mutations in second primary lung cancer.

Risk of Subsequent Primary Cancers After External Beam Radiotherapy Treatment of Pediatric Low Grade Gliomas: A Surveillance, Epidemiology, and End Results Analysis 1973 to 2015

Abstract INTRODUCTION Past studies have associated external beam radiotherapy (EBRT) with higher incidences of subsequent primary malignancies (SPMs). This link has been documented for leukemias, and prostate, thyroid, and bone cancers. However, the effects of EBRT on SPM development from low grade gliomas (LGGs) are not well understood. The aim of the present study was to characterize the risk of SPM development after EBRT treatment of LGGs. METHODS A total of 1439 pediatric (age 0-17) records between 1973 and 2015 were assembled from the Surveillance, Epidemiology, and End Results (SEER) database. Univariable and multivariable Cox regressions were used to evaluate the prognostic impact of demographic, tumor, and treatment-related covariates. Propensity score matching was used to balance baseline characteristics. Survival and cumulative hazard analyses measured the time to, and risk of, SPM development, stratified by receipt of EBRT. RESULTS Of the 1439 pediatric patients we analyzed, 450 received EBRT and 989 did not. A total of 65 pediatric patients were identified who developed SPMs after LGG diagnosis, and 35 of these patients received EBRT (OR: 2.70). Unadjusted Cox regressions revealed a significantly elevated SPM risk in EBRT-treated pediatric patients with LGGs (HR: 2.22, CI: 1.34-3.67). After adjusting for covariates such as race, gender, income, chemotherapy, and grade (World Health Organization I vs II), there was still a clear association between EBRT and the development of SPMs (HR: 2.52, CI: 1.50-4.23). Propensity score matching across covariates did not significantly impact the hazard ratio. Time-to-event Kaplan Meier curves demonstrated earlier SPM development in the EBRT-treated LGG pediatric population, and Nelson–Aalen cumulative hazard estimates showed higher incidences of SPM development at all time points. CONCLUSION EBRT treatment for LGGs is associated with an elevated incidence of SPMs, even after controlling for available covariates. This suggests less aggressive EBRT use in the pediatric LGG population may be warranted.

Identification of Myoferlin Expression for Prediction of Subsequent Primary Malignancy in Patients With Clear Cell Renal Cell Carcinoma.

Multiple primary malignant tumors are common in patients with renal cell carcinoma. However, reports on the factors that can identify patients with a risk for subsequent primary malignancies have been lacking. This study aimed to investigate whether myoferlin expression can be used as a potential marker to predict subsequent primary malignancies in patients with clear cell renal cell carcinoma (ccRCC). We evaluated the relationship of subsequent primary malignancies with clinicopathological factors and myoferlin expression in 152 patients with ccRCC, and we analyzed the strength of the association with myoferlin expression. The development of subsequent primary malignancies exhibited significant correlation with patient age (p=0.029), sex (p=0.015), T stage (p<0.001), and myoferlin expression (p=0.017). Furthermore, myoferlin hyperexpression was determined as an independent risk factor for developing a subsequent primary malignant tumor in patients with ccRCC (odds ratio(OR), 2.485, 95% Confidence Interval(CI)=1.052-5.870, p=0.038). Myoferlin hyperexpression can be a useful marker for predicting the development of subsequent primary malignancies in patients with ccRCC.

Risk of Second Primary Malignancies in Chronic Lymphocytic Leukemia

Introduction: Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia, with ~21,000 estimated new cases in 2018. Prior retrospective studies have suggested an increased risk of second primary malignancies (SPMs) in CLL patients. Population-based studies on the risk of SPMs in CLL are limited, especially in the last decade with improvements in prognostic and therapeutic tools over the last decade. As the survival of CLL patient improves, it may lead to more survivors who are at risk of developing SPMs. In this study, we sought to evaluate the risk of development of SPMs among CLL patients diagnosed from 2000-2014.Methods: We used the SEER 18 registries for the calculation of risk of SPMs and included CLL cases that were confirmed histologically between 2000-2014 (https://seer.cancer.gov/). SPMs diagnosed within 2 months of primary CLL diagnosis were excluded. Time to SPM was calculated by subtracting second malignancy survival/follow-up time from CLL survival/follow-up time. The SEER*Stat Multiple Primary-SIR tool was used to calculate SIRs for secondary malignancies by comparing these patients' subsequent cancer experience with the number of cancers that would be expected based on incidence rates for the general U.S. population. These analyses were adjusted for age, gender, race, and year of CLL diagnosis. Multivariate logistic regression was performed to identify factors associated with development of SPM.Results: The study cohort included 46,164 patients with CLL. After a median follow up of 50 months (range 1-179), 5220 (11.3%) patients developed a total of 5,738 subsequent malignancies. As compared to that of general population, CLL patients had a higher risk of developing SPMs (SIR: 1.40 [95%CI:1.37-1.44]) and the risk was much higher for hematologic malignancies (SIR: 2.63 [95%CI:2.47-2.80]) as compared to solid organ malignancies (SIR: 1.25 [95%CI: 1.22-1.29]).In addition to known common SPMs in CLL (lymphoma, melanoma, lung cancer, and prostate cancer), there was an elevated risk of developing acute lymphoblastic leukemia (SIR 5.43), chronic myeloid leukemia (SIR 2.18), thyroid cancer (SIR 2.09), and kidney cancer (SIR 1.70) (Table). Out of the 5220 patients who developed SPMs, 437 (8.3%) patients developed two subsequent second primary malignancies, and 81 (1.5%) patients developed > 2 subsequent primary cancers, which was significantly more than the endemic rate (SIR, 1.40; p <.05). Of the 5738 SPMs, 1095 (19%) occurred in 2-11 months, 2822 (49%) in 1-5 years, 1499 (26%) in 6-10 years and 321 (6%) beyond 10 years of CLL diagnosis (Figure).On logistic regression, males had higher odds of developing SPMs than females (OR: 1.46 [95% CI: 1.38-1.56], p<0.0001) and the patients diagnosed with from 2000-2007 had higher odds of developing SPMs as compared to those diagnosed from 2007-2014 (OR: 2.28 [95%CI: 2.15-2.42], p<0.0001]. The risk of developing SPM did not differ based on the age, race and between the patients who received first line therapy and no initial therapy. CLL patients who developed SPMs had significantly less median overall survival as compared to that of patients who did not develop SPMs (93 vs 109 months, p<0.05).Conclusion: In this large population-based study, CLL patients had an elevated risk of developing second primary hematologic and solid malignancies. The specific types of SPMs were varied, ranging from common ones such as lymphoma, lung cancer, prostate cancer, to uncommon ones such as thyroid cancer, kidney cancer, and chronic myeloid leukemia. The patients who were diagnosed after 2007 had a lower risk of developing SPMs as compared to those diagnosed before. There is a need for studies evaluating immunological repertoire of CLL and its impact on development of SPMs. Knowledge of these SPMs may help physicians with their early detection. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Other Primary Malignancies Among Women With Adult-Type Ovarian Granulosa Cell Tumors.

The aim of this study was to determine the incidence of new primary malignancies after adult-type granulosa cell tumor (AGCT) and the incidence of AGCT after breast and uterine cancer using nationwide population-based registry data. We used the Finnish Cancer Registry to identify all patients diagnosed with AGCT in 1968 to 2013 (n = 986). The number of subsequent primary malignancies among women with AGCT and the number of AGCTs in women with previous breast or uterine cancer were compared with the expected number of cases and expressed as standardized incidence ratios (SIRs). There were 122 cases of subsequent cancers diagnosed at least 6 months after the primary diagnosis of AGCT (SIR, 1.09; 95% confidence interval [CI], 0.91-1.3). In particular, the observed number of cancers of the soft tissue (SIR, 4.13; 95% CI, 1.33-12.8), thyroid (SIR, 3.42; 95% CI, 1.54-7.62), and leukemia (SIR, 2.67; 95% CI, 0.98-5.82) exceeded the number of expected cases. The SIR for breast cancers after AGCT was 1.26 (95% CI, 0.92-1.73), and the SIR for AGCT after breast cancer was 1.59 (95% CI, 1.04-2.29). The risk for subsequent AGCT was more than 2-fold in breast cancer patients younger than 50 years, and over 15 years after primary diagnosis. There is an increased risk for thyroid and soft tissue cancer as well as leukemia after AGCT, which may be associated with late effects of carcinogenic treatments and possibly shared risk factors. After breast cancer, the risk for AGCT was higher, which may indicate a shared hormonal etiology.

The PanCareSurFup consortium: research and guidelines to improve lives for survivors of childhood cancer

BackgroundSecond malignant neoplasms and cardiotoxicity are among the most serious and frequent adverse health outcomes experienced by childhood and adolescent cancer survivors (CCSs) and contribute significantly to their increased risk of premature mortality. Owing to differences in health-care systems, language and culture across the continent, Europe has had limited success in establishing multi-country collaborations needed to assemble the numbers of survivors required to clarify the health issues arising after successful cancer treatment. PanCareSurFup (PCSF) is the first pan-European project to evaluate some of the serious long-term health risks faced by survivors. This article sets out the overall rationale, methods and preliminary results of PCSF. MethodsThe PCSF consortium pooled data from 13 cancer registries and hospitals in 12 European countries to evaluate subsequent primary malignancies, cardiac disease and late mortality in survivors diagnosed between ages 0 and 20 years. In addition, PCSF integrated radiation dosimetry to sites of second malignancies and to the heart, developed evidence-based guidelines for long-term care and for transition services, and disseminated results to survivors and the public. ResultsWe identified 115,596 individuals diagnosed with cancer, of whom 83,333 were 5-year survivors and diagnosed from 1940 to 2011. This single data set forms the basis for cohort analyses of subsequent malignancies, cardiac disease and late mortality and case–control studies of subsequent malignancies and cardiac disease in 5-year survivors. ConclusionsPCSF delivered specific estimates of risk and comprehensive guidelines to help survivors and care-givers. The expected benefit is to provide every European CCS with improved access to care and better long-term health.

Surgical Resection and Outcome of Synchronous and Metachronous Primary Lung Cancer in Breast Cancer Patients.

Women with breast cancer are at increased risk of subsequent primary malignancies, specifically lung cancer. The aim of this study was to report the frequency of lung cancer in patients with breast cancer, and patients' characteristics and surgical outcomes. We investigated 1,066 consecutive female patients undergoing surgical resection for breast cancer and 666 undergoing surgical resection for lung cancer. Lung cancer with breast cancer was observed in 14 patients (1.3% of breast cancer and 2.1% of lung cancer cases; mean age=65 years), and 3/14 (21.4%) patients were smokers. Sixteen lung cancer lesions in 14 patients were adenocarcinomas and one was squamous cell carcinoma. All 14 patients were alive at the time of this report; 4/14 (28.6%) patients had recurrent breast cancer and 1/14 (7.1%) had recurrent lung cancer. In synchronous cases, 5/6 (83.3%) patients received concomitant surgery for both breast cancer and lung cancer. Patients' postoperative courses were uneventful. In metachronous cases, eight patients had lung cancer a mean of 33 months after breast cancer surgery. All eight patients received adjuvant therapies and 4/8 (50%) patients received adjuvant therapies for recurrent breast cancer, including chemotherapy, radiotherapy, hormonal therapy, and anti-HER2 therapy. All patients had early-stage lung adenocarcinoma and underwent surgical resection. Concomitant surgery for synchronous lung and breast cancer was feasible and safe. In metachronous cases, lung cancers tended to be detected within 3 years after surgery for breast cancer. Careful follow-up for postoperative breast cancer may contribute to the detection of early-stage lung cancer.

Subsequent primary malignancies after diffuse large B-cell lymphoma in the modern treatment era.

With the addition of rituximab and other treatment advances, survival after diffuse large B-cell lymphoma (DLBCL) has improved, but subsequent primary malignancies (SPMs) have emerged as an important challenge for DLBCL survivorship. We calculated standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for SPMs among 23879 patients who survived at least 1year after a first primary DLBCL diagnosed during 1989-2012, compared to the general population in California. Cumulative incidence (CMI) of SPMs, accounting for the competing risk of death, also was calculated. We found that the incidence of acute myeloid leukaemia (AML) nearly doubled in the post-rituximab era [SIR (95% CI) 4·39 (2·51-7·13) pre- (1989-2000) and 8·70 (6·62-11·22) post-rituximab (2001-2012)]. Subsequent thyroid cancer was rare pre-rituximab, but increased substantially after 2001 [0·66 (0·08-2·37) vs. 2·27(1·44-3·41)]. The 5-year CMI for all SPMs (4·77% pre- vs. 5·41% post-rituximab, P=0·047), AML (0·15% vs. 0·41%, P=0·003), thyroid cancer (0·03% vs. 0·15%, P=0·003) and melanoma (0·25% vs. 0·42%, P=0·020) were greater in DLBCL patients diagnosed in the post- versus pre-rituximab period. This study provides insight into the changing pattern of SPM occurrence after the introduction of rituximab, which may elucidate the aetiology of SPMs and should guide future cancer surveillance efforts among DLBCL patients.

Risk of subsequent primary malignancies among patients with prior colorectal cancer: a population-based cohort study.

BackgroundThe site-distribution pattern and relative risk of subsequent primary malignancies (SPMs) in colorectal cancer (CRC) patients remains to be determined.Materials and methodsA population-based cohort of 288,390 CRC patients diagnosed between 1973 and 2012 from the Surveillance, Epidemiology, and End Results database was retrospectively reviewed. Standardized incidence ratios were calculated to estimate the relative risk for SPMs.ResultsThe overall risk of SPMs increased in CRC patients (standardized incidence ratio 1.02) in the first 5 years after CRC diagnosis compared with that in the general population, and was negatively related to age at diagnosis. Risk increased significantly for cancers of the small intestine, ureter, colorectum, renal pelvis, endocrine system, and stomach, and decreased significantly for cancers of the gallbladder, liver, myeloma, and brain, as well as lymphoma. Patients with different prior CRC subsites showed specific sites at high risk of SPM. Prior right-sided colon cancer was associated with cancers of the small intestine, ureter, renal pelvis, thyroid, stomach, pancreas, and breast and prior left-sided colon cancer associated with secondary CRC, whereas rectal cancer was associated with cancers of the vagina, urinary bladder, and lung.ConclusionRisk of SPMs increases in CRC survivors, especially in the first 5 years after prior diagnosis. Intensive surveillance should be advocated among young patients, with specific attention to the small intestine, colorectum, renal pelvis, and ureter. The common sites at high risk of SPM originate from the embryonic endoderm. Genetic susceptibility may act as the main mechanism underlying the risk of multiple cancers.

Subsequent malignancies among long-term survivors of Hodgkin lymphoma and non-Hodgkin lymphoma: a pooled analysis of German cancer registry data (1990-2012).

The increased risk of subsequent primary malignancies (SPM) in survivors of adult-onset Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) remains a challenging clinical problem worldwide. The German cancer registry database, pooled from 14 federal states, was used to calculate the standardized incidence ratio (SIR) and excess absolute risk (EAR) of SPM in 128587 patients registered with first primary HL/NHL between 1990 and 2012. Conversely, SIRs were also calculated for a subsequent HL/NHL following other first cancers. The risk of developing SPM was significantly increased over twofold for HL survivors (SIR=2·14, EAR=51·87 cases/10000 person-years) and 1·5-fold for NHL survivors (SIR=1·48, EAR=55·23) compared with the general German population. For solid cancers, SIRs were significantly elevated (1·6- and 1·4-fold; respectively) and were highest (threefold) in patients below 30years of age upon initial diagnosis. Overall, SIRs were consistently elevated for lip/oral cavity, colon/rectum, lung, skin melanoma, breast, kidney and thyroid. Significantly increased SIRs for oesophagus, stomach, liver, pancreas, testis, prostate, and brain/central nervous system were observed following NHL only. For certain SPM, SIRs remained significantly elevated more than 10years following HL/NHL diagnosis. Positive reciprocal associations were demonstrated between HL/NHL and several solid cancers mentioned above; for some, common aetiological mechanisms seem plausible.

Subsequent primary malignancies (SPMs) after diffuse large B-cell lymphoma (DLBCL) in the modern treatment era.

7543Background: With advances in treatment, including the addition of rituximab, survival after DLBCL has improved such that managing SPMs has emerged as an important challenge. However, no populat...