Risk Of Subsequent Primary Cancer Research Articles

Risk of subsequent primary cancers in bladder cancer survivors

We aimed to investigate the risk of bladder cancer (BCa) survivors developing or dying from 15 specific-subsequent primary cancers (SPCs). A total of 229,554 BCa survivors were identified from the Surveillance, Epidemiology, and End Results database. Incidence and mortality per 10,000 person-years, absolute excess risk (AER) per 10,000 person-years, standardized incidence ratios, and standardized mortality ratios were calculated. Among BCa survivors, 38,207 developed SPCs and 17,546 died of SPCs. The risk of developing and dying from SPCs was significantly high for 10 and 6 of the 12 common SPCs in men, respectively, while for 6 and 5 of the 14 common SPCs in women, respectively. The SPCs with high risk of development in men were colorectal, breast, liver, and pancreatic cancer, and the ones with high risk of death were liver and pancreatic cancer. Moreover, SPCs with a high risk of development or death among young BCa survivors include ureter, kidney and renal pelvis, and lung cancer. In addition, BCa survivors within 1 year of diagnosis have a significantly higher risk of development and death from ureter, kidney and renal pelvis, prostate, and cervix cancer, but a lower risk of prostate cancer than the general population after 5 years of diagnosis. Lung cancer had a significantly high risk of development but a low risk of death. Among BCa survivors, the risk of developing or dying from few SPCs is significantly high. These findings may provide an important basis for clinical follow-up of BCa survivors.

Risk of subsequent primary cancers among adult cancer survivors.

10554 Background: Improvements in early detection and clinical management of cancers have led to a significant increase in long-term cancer survivors who may be at an elevated risk of developing a subsequent primary cancer (SPC). As the largest and most comprehensive analysis in Canada, we assessed the risks and patterns of SPC development among 134,693 adult cancer survivors with 852,661 person-years of follow-up. Methods: We used data from the Alberta Cancer Registry (ACR) to identify all first primary cancers (FPC) occurring between 2004 and 2015 to allow for adequate follow-up until December 31, 2020. A SPC was considered as the next primary cancer occurring in a different organ/site. We estimated incidence rates (IR) and standardized incidence ratios (SIR) for SPC development with 95% confidence intervals (CI). IRs were estimated as the observed number of SPC divided by the person-years of follow-up. SIRs were estimated as the observed number of SPC (O) divided by the expected number of SPC (E), where E is a weighted-sum of the general population-based year-age-sex-specific incidence rates and the corresponding person-years of follow-up among the adult cancer survivors. Results: The risk of developing a SPC up to fifteen years after an initial cancer was 16.1% for males and 12.3% for females. These risk estimates varied considerably by initial cancer site. Survivors of initial head and neck cancers had a fifteen-year cumulative incidence of 21.3% and a 2.5-fold relative risk of SPC development. Overall, both males (SIR=1.50) and females (SIR=1.64) had an increased risk of developing a SPC. Both male and female survivors of a FPC were at a significantly increased relative risk of developing a screen-detectable SPC (breast, cervical, colorectal, lung). There were significant increases in SPC risk for nearly all age groups, with a greater than 5-fold increase for survivors of early-onset cancers diagnosed between ages 18 to 39. Conclusions: Cancer survivors of nearly every FPC site had substantially increased risk of a SPC, compared to the cancer risk in the general population. Screen-detectable cancers were common SPC sites and this highlights the need to develop evidence-based guidelines for cancer screening in the growing population of long-term cancer survivors.[Table: see text]

Risk of Subsequent Primary Cancers Among Adult-Onset 5-Year Cancer Survivors in South Korea: Retrospective Cohort Study.

The number of cancer survivors who develop subsequent primary cancers (SPCs) is expected to increase. We evaluated the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types considering sex and age. We conducted a retrospective cohort study using the Health Insurance Review and Assessment database of South Korea including 5-year cancer survivors diagnosed with an FPC in 2009 to 2010 and followed them until December 31, 2019. We measured the SPC incidence per 10,000 person-years and the standardized incidence ratio (SIR) compared with the incidence expected in the general population. Among 266,241 survivors (mean age at FPC: 55.7 years; 149,352/266,241, 56.1% women), 7348 SPCs occurred during 1,003,008 person-years of follow-up (median 4.3 years), representing a 26% lower risk of developing SPCs (SIR 0.74, 95% CI 0.72-0.76). Overall, men with 14 of the 20 FPC types had a significantly lower risk of developing any SPCs; women with 7 of the 21 FPC types had a significantly lower risk of developing any SPCs. The risk of developing any SPC type differed by age; the risk was 28% higher in young (<40 years) cancer survivors (SIR 1.28, 95% CI 1.16-1.42; incidence: 30 per 10,000 person-years) and 27% lower in middle-aged and older (≥40 years) cancer survivors (SIR 0.73, 95% CI 0.71-0.74; incidence: 80 per 10,000 person-years) compared with the age-corresponding general population. The most common types of FPCs were mainly observed as SPCs in cancer survivors, with lung (21.6%) and prostate (15.2%) cancers in men and breast (18.9%) and lung (12.2%) cancers in women. The risks of brain cancer in colorectal cancer survivors, lung cancer in laryngeal cancer survivors, and both kidney cancer and leukemia in thyroid cancer survivors were significantly higher for both sexes. Other high-risk SPCs varied by FPC type and sex. Strong positive associations among smoking-related cancers, such as laryngeal, head and neck, lung, and esophageal cancers, were observed. Substantial variation existed in the associations between specific types of FPC and specific types of SPC risk, which may be linked to hereditary cancer syndrome: for women, the risks of ovarian cancer for breast cancer survivors and uterus cancers for colorectal cancer survivors, and for men, the risk of pancreas cancer for kidney cancer survivors. The varying risk for SPCs by age, sex, and FPC types in cancer survivors implies the necessity for tailored prevention and screening programs targeting cancer survivors. Lifestyle modifications, such as smoking cessation, are essential to reduce the risk of SPCs in cancer survivors. In addition, genetic testing, along with proactive cancer screening and prevention strategies, should be implemented for young cancer survivors because of their elevated risk of developing SPCs.

Risk of Subsequent Primary Cancers in Thyroid Cancer Survivors according to the Dose of Levothyroxine: A Nationwide Cohort Study.

Current research has not investigated the effect of thyroid-stimulating hormone suppression therapy with levothyroxine on the risk for developing subsequent primary cancers (SPCs). This study aimed to investigate the association between levothyroxine dosage and the risk for SPCs in thyroid cancer patients. We conducted a nationwide population-based retrospective cohort study form Korean National Health Insurance database. This cohort included 342,920 thyroid cancer patients between 2004 and 2018. Patients were divided into the non-levothyroxine and the levothyroxine groups, the latter consisting of four dosage subgroups according to quartiles. Cox proportional hazard models were performed to evaluate the risk for SPCs by adjusting for variables including cumulative doses of radioactive iodine (RAI) therapy. A total of 17,410 SPC cases were observed over a median 7.3 years of follow-up. The high-dose levothyroxine subgroups (Q3 and Q4) had a higher risk for SPC (adjusted hazard ratio [HR], 1.14 and 1.27; 95% confidence interval [CI], 1.05-1.24 and 1.17- 1.37; respectively) compared to the non-levothyroxine group. In particular, the adjusted HR of stomach (1.31), colorectal (1.60), liver and biliary tract (1.95), and pancreatic (2.48) cancers were increased in the Q4 subgroup. We consistently observed a positive association between high levothyroxine dosage per body weight and risk of SPCs, even after adjusting for various confounding variables. Moreover, similar results were identified in the stratified analyses according to thyroidectomy type and RAI therapy, as well as in a subgroup analysis of patients with good adherence. High-dose levothyroxine use was associated with increased risk of SPCs among thyroid cancer patients regardless of RAI therapy.

Factors associated with the onset and survival of subsequent primary breast cancer in female non‐metastatic breast cancer survivors

AbstractThis study aimed to investigate the risk factors for the onset of subsequent primary breast cancer (SPBC) in women with a previous diagnosis of early‐stage breast cancer (BC) and to construct a prognostic prediction model for patients with SPBC. Using the Surveillance, Epidemiology, and End Results‐17 (SEER‐17) database, we conducted a retrospective cohort analysis on women with initial primary early‐stage BC from 2004 to 2015. Standardized incidence ratio (SIR) was calculated to determine the risk of subsequent primary cancer (SPC). A competing risk model was built to identify the risk factors for the onset of SPBC. And risk factors associated with breast cancer‐specific mortality in SPBC patients were evaluated and presented in the form of nomogram. Compared with the general population, the overall risk of SPC for all sites was significantly elevated in women with early‐stage BC (SIR = 1.21, 95% CI: 1.20–1.23), and breast is the most frequent site. Age, race and ethnicity, year of diagnosis, history of other tumors, histological type, surgery, radiation, chemotherapy, tumor size, positive lymph nodes numbers and ER status were independent risk factors (p &lt; .05) for the onset of SPBC. A new prognosis nomogram demonstrated good discrimination after internal validation with a C‐index of 0.869 (95% CI: 0.859–0.880), and showed favorable consistency and clinical usefulness. The incidence of SPBC and prognosis of patients with SPBC were well estimated based on a large cohort. Our nomogram model had excellent prediction performance and could be a useful tool to predict prognosis.

Risk of Subsequent Primary Cancer in Thyroid Cancer Survivors: A Nationwide Population-Based Study.

Background: Despite obtaining a good prognosis and long life expectancy, survivors of thyroid cancer can nevertheless develop subsequent primary cancer (SPC). We investigated the risk and types of SPC in patients with thyroid cancer and compared them with subjects without thyroid cancer history (controls). Methods: We conducted a nationwide, population-based, retrospective cohort study based on the Korean National Health Insurance Database. A total of 432,654 patients diagnosed with thyroid cancer between 2004 and 2019 were 1:1 matched with controls for age, sex, income, and region of residence. The hazard ratios (HR) and 95% confidence intervals (CI) of SPC were estimated using Cox proportional hazard models. Results: In total, 78,584 (18.2%) patients with thyroid cancer and 49,979 (11.6%) controls were diagnosed with SPCs over a mean follow-up of 6.9 years. Patients with thyroid cancer had a higher risk of SPC at any site (adjusted HR, 1.62; 95% CI, 1.60-1.64) than the controls. The risk of SPCs was particularly high for patients diagnosed with thyroid cancer at a younger age (<40 years) and within 5 years. Conclusions: Medical caregivers should consider the long-term follow-up of patients with thyroid cancer and discuss the risk of SPC, especially if they complain of cancer-related symptoms.

Association of first primary cancer with risk of subsequent primary cancer among survivors of adult-onset cancers in Kentucky and Appalachian Kentucky.

Appalachia is a region with significant cancer disparities in incidence and mortality compared to Kentucky and the United States. However, the contribution of these cancer health disparities to subsequent primary cancers (SPCs) among survivors of adult-onset cancers is limited. This study aimed to quantify the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types, residence and sex. This retrospective cohort study from the Kentucky Cancer Registry included 148,509 individuals aged 20-84 years diagnosed with FPCs from 2000-2014 (followed until December 31, 2019) and survived at least 5 years. Expected numbers of SPC were derived from incidence rates in the Kentucky population; standardized incidence ratio (SIR) compared with those expected in the general Kentucky population. Among 148,509 survivors (50.2% women, 27.9% Appalachian), 17,970 SPC cases occurred during 829,530 person-years of follow-up (mean, 5.6 years). Among men, the overall risk of developing any SPCs was statistically significantly higher for 20 of the 30 FPC types, as compared with risks in the general population. Among women, the overall risk of developing any SPCs was statistically significantly higher for 20 of the 31 FPC types, as compared to the general population. The highest overall SIR were estimated among oral cancer survivors (SIR, 2.14 [95% CI, 1.97-2.33] among men, and among laryngeal cancer survivors (SIR, 3.62 [95% CI, 2.93-4.42], among women. Appalachian survivors had significantly increased risk of overall SPC and different site specific SPC when compared to non-Appalachian survivors. The highest overall SIR were estimated among laryngeal cancer survivors for both Appalachian and non-Appalachian residents (SIR, 2.50: 95%CI, 2.10-2.95; SIR, 2.02: 95% CI, 1.77-2.03, respectively). Among adult-onset cancer survivors in Kentucky, several FPC types were significantly associated with greater risk of developing an SPC, compared with the general population. Risk for Appalachian survivors was even higher when compared to non-Appalachian residents, but was not explained by higher risk of smoking related cancers. Cancers associated with smoking comprised substantial proportions of overall SPC incidence among all survivors and highlight the importance of ongoing surveillance and efforts to prevent new cancers among survivors.

A randomized phase III study assessing the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors.

TPS10617 Background: Lung cancer survivors are highly enriched for extensive smoking histories and have an increased risk of subsequent primary cancers, including those of the larynx, mouth and throat, esophagus, pancreas, bladder, thyroid, stomach, small intestine, colon, rectum, and kidney. Guideline-concordant surveillance after definitive treatment for lung cancer consists of periodic chest CT scans, which do not visualize the majority of second malignancies that this population ultimately develops. Disadvantaged and minority patients are diagnosed with recurrence and second primary cancers at later stages due to reduced compliance with survivorship surveillance. To address these issues, we propose utilizing multi-cancer early detection (MCED) liquid biopsies. MCED liquid biopsies are part of a rapidly growing field of research that assesses parallel cancer screening for multiple cancer types with point of care blood, urine, or saliva sampling. We selected a methylation-based screening liquid biopsy for multiple reasons: 1) it has the highest PPV and specificity of any test clinically validated in the multi-cancer detection setting thus far, 2) it produces a tissue of origin, allowing for targeted workup of positive findings, and 3) it requires only a single test, which we believe will minimize attrition among vulnerable populations with decreased access to healthcare. We designed a 9,000-patient prospective, multi-institutional randomized clinical trial to assess the efficacy of liquid biopsy in early diagnosis of recurrence and second malignancies in lung cancer survivors. To ensure over 25% of participants are of minority status, we have recruited multiple community hospitals to the study in partnership with Memorial Sloan Kettering Cancer Center. Patients included in this study are survivors of non-metastatic non- small cell lung cancer, status-post definitive treatment (surgery or radiation) with no evidence of disease for at least one year. Participants will be randomized 1:1 to standard surveillance or standard surveillance plus six-monthly methylation-based liquid biopsy tests over a two-year study period, and strict guidelines on follow-up of positive liquid biopsy testing will be provided to reduce harms from false positives or over-diagnosis. Methods: The primary endpoint of this study is the incidence of late stage cancer (distant recurrence or new primary cancer of stage III/IV). Secondary endpoints include cancer-specific mortality, eligibility for definitive interventions once cancer is diagnosed, and utilization of liquid biopsy versus standard of care scans. This is the first randomized controlled trial of screening liquid biopsy in a survivorship population and the first trial utilizing liquid biopsy in a large minority population.

Prevalence and Spectrum of Second Primary Malignancies among People Living with HIV in the French Dat'AIDS Cohort.

Simple SummaryPeople who survive primary cancers are at an increased risk for subsequent primary cancers. An increased risk for certain types of primary cancers among people living with HIV (PLWH) was demonstrated in the last few decades. Given the increasing life expectancy of PLWH, a steady increase in SPC has been reported. The main objective of this study was to describe the prevalence and spectrum of second primary cancers (SPCs) stratified by first primary cancers in HIV-positive men and women cancer survivors. We showed that the pattern of SPCs differs from that observed in the general population and according to sex. Yet, further studies are needed to determine the excess risk of SPCs in this population and to confirm the need for more appropriate screening procedures.Background: We aimed to describe the prevalence and spectrum of second primary cancer (SPC) in HIV-positive cancer survivors. Methods: A multicenter retrospective study was performed using longitudinal data from the French Dat’AIDS cohort. Subjects who had developed at least two primary cancers were selected. The spectrum of SPCs was stratified by the first primary cancer type and by sex. Results: Among the 44,642 patients in the Dat’AIDS cohort, 4855 were diagnosed with cancer between 1 December 1983 and 31 December 2015, of whom 444 (9.1%) developed at least two primary cancers. The most common SPCs in men were non-Hodgkin lymphoma (NHL) (22.8%), skin carcinoma (10%) and Kaposi sarcoma (KS) (8.4%), and in women the most common SPCs were breast cancer (16%), skin carcinoma (9.3%) and NHL (8%). The pattern of SPCs differed according to first primary cancer and by sex: in men, NHL was the most common SPC after primary KS and KS was the most common SPC after primary NHL; while in women, breast cancer was the most common SPC after primary NHL and primary breast cancer. Conclusion: The frequency and pattern of subsequent cancers among HIV-positive cancer survivors differed according to the first primary cancer type and sex.

Subsequent primary cancers among survivors of adolescent and young adult onset cancers in the United States.

10604 Background: Adolescent and young adult (AYA) cancer survivors are at increased risk of subsequent primary cancer (SPC); however, a comprehensive examination of risk patterns across cancer types is lacking in the U.S. Methods: SPC incidence and mortality was calculated among &gt;1-year cancer survivors aged 15 to 39 years at first primary cancer (FPC) diagnosis during 1992-2016 in 12 Surveillance, Epidemiology, and End Results registries. Rates were expressed as number of cases/deaths per 10,000 person-years and compared with those expected in the general population using standardized incidence (SIR) and standardized mortality ratios (SMR). Results: Among 202,440 survivors of AYA-onset cancers (mean age at FPC diagnosis, 31.8 years; 60.7% women), 6,675 SPC cases (34.3 per 10,000) and 3,786 SPC deaths (19.4 per 10,000) occurred during 1,955,119 person-years of follow-up (mean, 9.7 years), corresponding to an SIR of 1.58 (95%CI = 1.54-1.62) and SMR of 4.19 (95%CI = 4.06-4.33. In men, overall incidence and mortality SPC rates were statistically significantly higher for each of 21 FPC types compared with risks in the general population, except for thyroid cancer mortality. In women, risk was statistically significantly higher for 14/23 FPC types for incidence and 19/23 FPC types for mortality. SIRs were highest in survivors of pancreatic cancer (SIR = 5.68, 95% CI = 2.94-9.93; 84 per 10,000), Kaposi sarcoma (SIR = 5.15, 95%CI = 4.62-5.73; 116 per 10,000) and liver cancer (SIR = 4.97, 95%CI = 2.57-8.68; 68.4 per 10,000) in men, and acute lymphoid leukemia (SIR, 3.27, 95% CI = 2.22-4.64; 49.5 per 10,000), Hodgkin lymphoma (SIR = 2.47, 95% CI = 2.22-2.73; 51.6 per 10,000), and bone sarcoma (SIR = 2.41, 95%CI = 1.80-3.16; 47.6 per 10,000) in women. SMRs were highest in survivors of pancreatic cancer, acute lymphoid leukemia, and stomach cancer in men, and liver cancer, acute lymphoid leukemia, and soft tissue sarcoma in women. Conclusions: Overall and type-specific risk patterns of SPCs among AYA cancer survivors differ considerably across FPC type, highlighting the need for targeted approaches for cancer prevention and surveillance in survivorship care planning.

Subsequent Cancer in Survivors of First Primary Cancers

Survivors of first primary cancers have excess risk for subsequent primary cancers. In this retrospective cohort study, researchers quantified that

Determinants of Second Primary Cancer Type in Survivors of Virus-Related and Non-Virus-Related Cancer Living With HIV in the French Dat'AIDS Cohort.

ObjectivesPeople who survive after primary cancer are at an increased risk for subsequent primary cancers. We aimed to investigate the possible determinants of second primary cancer (SPC) in HIV-positive cancer survivors.MethodsThis was a multicenter retrospective study using longitudinal data from the French Dat’AIDS cohort. Subjects who developed at least 2 primary cancers were selected. Cancer cases were identified using ICD10 codes and distributed in 3 cancer categories: AIDS-defining cancer (ADC), virus-related non-ADC (VR-NADC), and virus-unrelated-NADC (VU-NADC). The possible determinants considered were the first primary cancer category, sex, age, HIV transmission route, duration of HIV infection follow-up, duration of ART exposure, nadir CD4+ T cell count, and hepatitis C and hepatitis B serostatus.ResultsAmong the 44642 patients in the Dat’AIDS cohort, 4855 were diagnosed with cancer between 1 December 1983 and 31 December 2015, of whom 444 (9.1%) developed at least 2 primary cancers: 130 ADCs, 85 VR-NADCs, and 229 VU-NADCs. A longer delay between the first primary cancer and the SPC was associated with an increased risk of occurrence of a VR-NADC rather than a secondary ADC. Having had a first primary VU-NADC, an older age, and a longer delay between the HIV diagnosis and the first primary cancer as well as between the first primary cancer and the SPC were associated with an increased risk of VU-NADC rather than ADC.ConclusionSPCs are now a major concern in HIV-positive cancer survivors justifying the development of monitoring strategies after a first cancer.

Association of First Primary Cancer With Risk of Subsequent Primary Cancer Among Survivors of Adult-Onset Cancers in the United States

The number of cancer survivors who develop new cancers is projected to increase, but comprehensive data on the risk of subsequent primary cancers (SPCs) among survivors of adult-onset cancers are limited. To quantify the overall and cancer type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer (FPC) types and sex. A retrospective cohort study from 12 Surveillance, Epidemiology, and End Results registries in the United States, that included 1 537 101 persons aged 20 to 84 years diagnosed with FPCs from 1992-2011 (followed up until December 31, 2017) and who survived at least 5 years. First primary cancer. Incidence and mortality of SPCs per 10 000 person-years; standardized incidence ratio (SIR) and standardized mortality ratio (SMR) compared with those expected in the general population. Among 1 537 101 survivors (mean age, 60.4 years; 48.8% women), 156 442 SPC cases and 88 818 SPC deaths occurred during 11 197 890 person-years of follow-up (mean, 7.3 years). Among men, the overall risk of developing any SPCs was statistically significantly higher for 18 of the 30 FPC types, and risk of dying from any SPCs was statistically significantly higher for 27 of 30 FPC types as compared with risks in the general population. Among women, the overall risk of developing any SPCs was statistically significantly higher for 21 of the 31 FPC types, and risk of dying from any SPCs was statistically significantly higher for 28 of 31 FPC types as compared with risks in the general population. The highest overall SIR and SMR were estimated among survivors of laryngeal cancer (SIR, 1.75 [95% CI, 1.68-1.83]; incidence, 373 per 10 000 person-years) and gallbladder cancer (SMR, 3.82 [95% CI, 3.31-4.39]; mortality, 341 per 10 000 person-years) among men, and among survivors of laryngeal cancer (SIR, 2.48 [95% CI, 2.27-2.72]; incidence, 336 per 10 000 person-years; SMR, 4.56 [95% CI, 4.11-5.06]; mortality, 268 per 10 000 person-years) among women. Substantial variation existed in the associations of specific types of FPCs with specific types of SPC risk; however, only a few smoking- or obesity-associated SPCs, such as lung, urinary bladder, oral cavity/pharynx, colorectal, pancreatic, uterine corpus, and liver cancers constituted considerable proportions of the total incidence and mortality, with lung cancer alone accounting for 31% to 33% of mortality from all SPCs. Among survivors of adult-onset cancers in the United States, several types of primary cancer were significantly associated with greater risk of developing and dying from an SPC, compared with the general population. Cancers associated with smoking or obesity comprised substantial proportions of overall SPC incidence and mortality among all survivors and highlight the importance of ongoing surveillance and efforts to prevent new cancers among survivors.

Incorporating the Risk for Subsequent Primary Cancers Into the Care of Adult Cancer Survivors

Incorporating the Risk for Subsequent Primary Cancers Into the Care of Adult Cancer Survivors

The Role of Lymphomas in Subsequent Primary Cancers in People with HIV/AIDS: An Australian National Population-Based Data Linkage Study

Background Despite combination antiretroviral therapy (cART), the incidence of lymphomas remains elevated in persons with HIV/AIDS (PWHA). While the risk of subsequent primary cancers (SPCs) in the general population is well understood, these data are lacking for PWHA. Underlying aetiologic factors in PWHA, including oncogenic viruses and immunodeficiency, may have a differential impact on SPCs. We conducted a nationwide data linkage study in order to examine the role of lymphoma in SPCs in PWHA in two ways. First, we determined the incidence of and risk factors for Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL) (including chronic lymphocytic leukaemia) in PWHA previously diagnosed with an initial cancer of any type. Second, we assessed the incidence and features of SPCs of any type in PWHA after a primary HL or NHL. Methods Since 1982 Australia has had compulsory disease notification of all new HIV infections and all invasive cancers. We conducted a probabilistic data linkage study between the Australian National HIV Registry, the Australian Cancer Database and National Death Index to identify PWHA diagnosed with an initial cancer, followed by at least one SPC between 1982 and 2012. Follow up commenced from 90 days post the date of first cancer diagnosis at or following HIV diagnosis, and ended on 31 December 2012 or death, whichever came earlier. A SPC was defined as a cancer of diverse site and histology to the first cancer and diagnosed more than 90 days later (in order to mitigate ascertainment bias). The incidence of SPC was compared using Poisson regression. Risk factors considered included: age, sex, HIV exposure modality (such as male-to-male, intravenous drug, etc.) and CD4+ cell count at HIV diagnosis (&amp;lt;50, 50-199, 200-499, &amp;gt;500 cells/µL). Incidence was also compared across various eras corresponding to HIV treatment advances: 1982-1995 (pre-cART); 1996-1999 (early-cART); 2000-2004 (availability of protease inhibitors for HIV); and, 2005-2012 (availability of fusion inhibitors for HIV and rituximab for CD20-positive lymphomas). Results Out of 28,696 PWHA, 3,548 were identified with a first cancer. Among them, 229 SPCs were identified over 27,398 person-years (PY) of follow-up. The crude incidence of SPCs was 8.36 per 1000 PY (95% CI 7.34-9.51). Of 229 SPCs, 88 were lymphomas, comprising 42 diffuse large B cell, 4 Burkitt, 3 T cell, 2 primary effusion, 3 low grade lymphomas and 5 HLs; 29 NHLs were not sub-classified in the Database. The majority of first cancers in the group with SPCs were Kaposi sarcoma (KS) (55%). The incidence of lymphoma as an SPC decreased from 8.10 to 0.79 per 1000 PY from 1982-1995 to 2005-2012 (p=0.003). Median time from first cancer diagnosis to the diagnosis of a lymphoma SPC was 2.0 years (interquartile range (IQR): 0.8-4.0). Median age at diagnosis of a lymphoma SPC was 39 years (IQR: 34-49). The risk of a lymphoma SPC decreased with older age, from 10.68 per 1000 PY in those under 35 to 1.28 per 1000 PY in those above 55 (p=0.003). CD4 count at HIV diagnosis and HIV exposure modality were not associated with the risk of a lymphoma SPC. The incidence of a SPC after lymphoma as a first cancer (n=39) was 5.60 per 1000 PY, versus 9.30 per 1000 PY when the first cancer was not lymphoma (n=190, p=0.004). KS was the most common SPC after an initial lymphoma (49% of cases). Only two myeloid SPCs occurred. Median time to diagnosis of SPC after an initial lymphoma was 2.6 years (IQR: 1.1-6.7). Risk of a SPC after a first lymphoma increased significantly from 4.12 per 1000 person-years in those diagnosed with HIV in the 1982-1995 pre-cART era, to 33.15 per 1000 person-years in patients diagnosed with HIV between 2009-2012 (p=0.005). Conclusion The incidence and spectrum of SPC in PWHA is increasingly important as overall and cancer-specific survival of these patients continues to improve. The incidence of lymphomas as SPC in PWHA has decreased over time, which may be a function of improved HIV treatment and reduced susceptibility to immunosuppression-related lymphoma. However, PWHA diagnosed with lymphoma as a first cancer are experiencing increasing incidence of SPCs, occurring after relatively short intervals. Longer survival is likely contributing to this effect. Importantly, therapy-related cancers do not appear prominent, suggesting HIV-specific factors may play a role. These findings emphasise the importance of SPC surveillance tailored to this special population. Disclosures Di Ciaccio: Janssen: Honoraria.

Patterns of the risk for subsequent primary cancer among survivors of adult-onset cancers in the United States.

12060 Background: The number of cancer survivors who develop new cancers is projected to grow in the US. Few studies, however, have provided a comprehensive overview of the contemporary pattern in the risk of subsequent primary cancer (SPC) among survivors of adult-onset cancers. Herein, we evaluate overall and type-specific risks of SPCs among adult-onset cancer survivors by first primary cancer types and sex. Methods: We assessed the excess risk of SPCs among 1,442,374 persons aged 20-84 years who were diagnosed with first primary cancers from 1992-2010 and survived ≥5 years in the 12 Surveillance, Epidemiology, and End Results registries. We expressed the risks using excess absolute risk (EAR) per 10,000 person-years and standardized incidence ratio (SIR) by first primary cancer types and sex, compared to those expected in the general population. We also estimated percent contributions of each specific type of SPCs to the total EAR for all first primary cancers combined by sex. Results: The overall risk of SPCs was higher than expected for 24 of the 34 first primary types among male survivors and for 28 of the 35 first primary types among female survivors. The greatest SIR and EAR were estimated after laryngeal cancer in both men (SIR = 1.74, 95%CI = 1.67-1.82; EAR = 159.3, 95%CI = 143.6-175.5) and women (SIR = 2.48, 95% CI = 2.26-2.73; EAR = 202.7; 95%CI = 171.8-236). There were 290 type-specific associations with significantly higher risk of SPC, 36% of which being reciprocal, predominantly among smoking-associated, HPV-associated, and hematologic cancers. The SIRs in men ranged from 1.05 (95%CI = 1.00-1.10; EAR = 1.69) for lung/bronchus cancer after colorectal cancer to 73.9 (95%CI = 58.3-92.3; EAR = 23.3) for anal cancer after Kaposi sarcoma; and in women the SIRs ranged from 1.08 (95%CI = 1.02-1.15; EAR = 0.36) for pancreatic cancer after breast cancer to 19.9 (95%CI = 15.0-26.0; EAR = 39.5) for oral cavity/pharyngeal cancer after laryngeal cancer. For all first primary cancers combined, lung/bronchus cancer comprised the greatest proportion of the total EAR of SPCs, 34.6% in men and 29.1% in women, followed by urinary bladder (11.8%) and oral cavity/pharynx (7.5%) in men and by corpus uterus (12.9%) and colorectum (7.6%) in women. Conclusions: Despite the substantial heterogeneity in the risk of SPCs across the first primary types, only a few cancers comprised a considerable proportion of the total excess risk among survivors. Better understanding of contributing factors to these patterns will inform survivorship care plans and care delivery.

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.

Incidence of first and second primary cancers diagnosed among people with HIV, 1985–2013: a population-based, registry linkage study

Cancer survivors are at increased risk for subsequent primary cancers. People living with HIV are at increased risk for AIDS-defining and non-AIDS-defining cancers, but little is known about their risk of first versus second primary cancers. We identified first and second primary cancers that occurred in above population expected numbers among people diagnosed with HIV in San Francisco, and compared first and second cancer incidence across five time periods that corresponded to important advances in antiretroviral therapy. In this population-based study, we used the San Francisco HIV/AIDS case registry to identify people aged 16 years and older who were diagnosed with HIV/AIDS in San Francisco (CA, USA) between Jan 1, 1990, and Dec 31, 2010. We computer-matched records from the registry with the California Cancer Registry to identify primary cancers diagnosed between Jan 1, 1985, and Dec 31, 2013. We calculated year, age, sex, and race adjusted standardised incidence ratios with exact 95% CIs and trends in incidence of first and second AIDS-defining and non-AIDS-defining cancers from 1985 to 2013. Of the 22 623 people diagnosed with HIV between Jan 1, 1990, and Dec 31, 2010, we identified 5655 incident primary cancers. We excluded 48 cancers with invalid cancer sequence numbers and 1062 in-situ anal cancers, leaving 4545 incident primary cancers, comprising 4144 first primary cancers, 372 second primary cancers, 26 third primary cancers, and three fourth or later primary cancers. First primary cancer standardised incidence ratios were elevated for Kaposi sarcoma (127, 95% CI 121-132), non-Hodgkin lymphoma (17·2, 16·1-18·4), invasive cervical cancer (8·0, 4·1-11·9), anal cancer (46·7, 39·7-53·6), vulvar cancer (13·3, 6·1-20·6), Hodgkin's lymphoma (10·4, 8·4-12·5), eye and orbit cancer (4·2, 1·4-6·9), lip cancer (3·8, 1·3-6·2), penile cancer (3·8, 1·4-6·1), liver cancer (3·0, 2·3-3·7), miscellaneous cancer (2·3, 1·7-3·0), testicular cancer (2·0, 1·4-2·6), tongue cancer (1·9, 1·1-2·7), and lung cancer (1·3, 95% CI 1·1-1·6). Second primary cancer risks were increased for Kaposi sarcoma (28·0, 95% CI 20·2-35·9), anal cancer (17·0, 10·2-23·8), non-Hodgkin lymphoma (11·1, 9·3-12·8), Hodgkin's lymphoma (5·4, 1·1-9·7), and liver cancer (3·6, 1·4-5·8). We observed lower first primary cancer standardised incidence ratios for prostate cancer (0·6, 95% CI 0·5-0·7), colon cancer (0·6, 0·4-0·8), and pancreatic cancer (0·6, 0·3-1·0), and lower second primary cancer standardised incidence ratios for testicular cancer (0·3, 0·0-0·9), kidney cancer (0·4, 0·0-0·9), and prostate cancer (0·6, 0·2-0·9). First and second primary AIDS-defining cancer incidence declined, and second primary non-AIDS-defining cancer incidence increased over time. Because of an increased risk for both first and second primary cancers, enhanced cancer prevention, screening, and treatment efforts are needed for people living with HIV both before and after initial cancer diagnosis. University of California San Francisco and US Centers for Disease Control and Prevention.

The burdens of lung cancer involved multiple primary cancers and its occurring patterns\u2013SEER Analysis between 1973 and 2006

The prognosis of malignancies has improved in recent years, subsequent primary cancers (SPCs) have become more frequent. This study investigates the patterns of lung cancer involved multiple primary cancers. We enrolled 206,619 primary lung cancer patients and 2,071,922 patients with other primary malignancies from Surveillance, Epidemiology and End Results (SEER) database. Observed annual risk (OAR) and absolute numbers were used to describe the risk of SPC and observed cases of SPC per 10,000 person-years at risk. Overall, OAR of SPCs following lung cancer was 176.28. At follow-up, 41.26% of SPCs occurred within 12–59 months while the highest OAR appeared after 120 months. The overall OAR of subsequent lung cancer after other malignancies was 27.90. Overall, the highest OAR and the highest absolute numbers of subsequent lung cancers were noticed 60–119 months and over 120 months post-diagnosis, respectively. Ten related cancers were listed. Our findings encourage surveillance for 10 common SPCs in lung cancer survivors during follow-up as well as screening for lung cancer after 10 common malignancies.

Increased serological cancer-associated biomarker levels at large bowel endoscopy and risk of subsequent primary cancer

Background: Frequently, subjects offered colonoscopy due to symptoms of colorectal neoplasia are diagnosed with diverticula. The symptoms may, however, also be related to extra-colonic neoplasia. The present retrospective study evaluated a possible association between increased levels of predefined biomarkers in subjects diagnosed with diverticula and risk of developing a primary malignant disease.Methods: During 2004/2005, about 4509 subjects were included in a multicenter study with collection of blood samples before bowel endoscopy. The aim was to evaluate a relation between the protein biomarkers CEA, TIMP-1, CA19-9 and YKL-40 and findings at endoscopy. Diverticula were diagnosed in 1021 subjects. By 31 December 2012, subjects who had developed primary malignancy were identified retrospectively and relation between biomarker levels at endoscopy and risk of developing primary malignancy was calculated. The relation with the four biomarkers was divided into three groups: 0 = none increased; 1 = one increased and 2 = two or more increased.Results: In the observation period, 148 subjects developed a primary malignant disease. Univariable analyzes of the biomarker levels showed that CEA, TIMP-1 and CA19-9 were significantly associated with development of primary malignancy. A multivariable analysis showed that increased levels were associated with development of malignancy (p < 0.0001). The 1- and 5-year cumulative risks of being diagnosed with a primary malignancy were: group 0: 1.1%/5.5%; group 1: 4.2%/10.1% and group 2: 11.4%/18.8%, respectively.Conclusion: Increased levels of CEA, TIMP-1 and CA19-9 at endoscopy with findings of diverticula were associated with a significantly increased risk of being diagnosed with a subsequent primary malignant disease.