Multiple Primary Standardized Incidence Ratio Research Articles

Risk and prognosis of secondary lung cancer after radiation therapy for thoracic malignancies.

Radiation therapy (RT) may increase the risk of second cancer. This study aimed to determine the association between exposure to radiotherapy for the treatment of thoracic cancer (TC) and subsequent secondary lung cancer (SLC). The Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for TC. Univariate Cox regression analyses and multiple primary standardized incidence ratios (SIRs) were used to assess the risk of SLC. Subgroup analyses of patients stratified by latency time since TC diagnosis, age at TC diagnosis, and calendar year of TC diagnosis stage were also performed. Overall survival and SLC-related death were compared among the RT and no radiation therapy (NRT) groups by using Kaplan-Meier analysis and competitive risk analysis. In a total of 329 129 observations, 147 847 of whom had been treated with RT. And 6799 patients developed SLC. Receiving radiotherapy was related to a higher risk of developing SLC for TC patients (adjusted HR, 1.25; 95% CI, 1.19-1.32; P < 0.001). The cumulative incidence of developing SLC in TC patients with RT (3.8%) was higher than the cumulative incidence (2.9%) in TC patients with NRT(P). The incidence risk of SLC in TC patients who received radiotherapy was significantly higher than the US general population (SIR, 1.19; 95% CI, 1.14-1.23; P < 0.050). Radiotherapy for TC was associated with higher risks of developing SLC compared with patients unexposed to radiotherapy.

Cardiovascular-Related Mortality Risk in Primary Myelofibrosis in Pre-Ruxolitinib and Ruxolitinib Eras

Background Ruxolitinib, a Janus Kinase inhibitor, was approved in 2011 for the treatment of primary myelofibrosis (PMF) and has shown improved survival since its introduction. However, there are reports of possible cardiotoxicity linked to the medication. 1,2 Previous studies have shown that cardiovascular disease (CVD) was the third most common cause of death in PMF. 3 Given that patients with PMF may need therapy for several years, the cardiovascular safety profile of ruxolitinib has been the subject of increased scrutiny. Our goal was to compare the cardiovascular-related mortality (CVM) risk in patients with PMF in the pre-ruxolitinib (pre-Rux) and ruxolitinib (Rux) eras. Methods Using the Surveillance, Epidemiology, and End-result (SEER) Research Plus Data, 17 Registries and Multiple Primary Standardized Incidence Ratio (MP-SIR) registries (2000 - 2020), a retrospective study of patients diagnosed with PMF between 2003 and 2019 was conducted. This period was split into the pre-Rux (2003-2010) and post-approval Rux eras (2012-2019) and compared the standard mortality ratios (SMRs) of CVD in both periods. SMR was expressed as the ratio of cardiovascular deaths observed in PMF to those expected in the general population. Descriptive statistics (frequencies) were compared with Chi-square. The Kaplan-Meier method was used to estimate cumulative relative survival (CRS), and the sub-distribution hazard model for competing risk analysis was used to predict CVM; the significance test was set at &amp;lt;0.05. Results 4,509 patients with PMF were identified between the two study periods (2003-2010 and 2012-2019). As shown in Table 1, a higher proportion of older patients aged 65+ years (67.2% vs. 62.9%, p=0.003) and Non-Hispanic Blacks (8.9% vs. 7.5%, p=0.025) were diagnosed in the Rux era. More patients were alive (49.6% vs. 16.6%, p&amp;lt;0.001), and 5-year CRS was higher in the Rux period (57.1% vs. 47.6%). There was no significant difference in the proportion of deaths due to cardiovascular disease between the two periods. Compared to the general population, patients with PMF had a higher overall CVM independent of the era of diagnosis ( Figure 1). However, there was a decrease in SMR of overall CVD in the post-Rux period (SMR=2.67; 95% CI: 2.28-3.10) compared to the pre-Rux (SMR: 3.42; 95% CI: 2.79-4.15). In terms of specific CVD, the SMRs of diseases of the heart, hypertension without heart diseases, and cerebrovascular disease were higher in the pre-RUX period compared to the Rux era, where SMR was higher only in diseases of the heart, which was still lower than the pre-Rux period (SMR: 2.73 [2.28-3.24] vs. 3.57 [2.84-4.44]). There was no significant difference in the mortality risk from other CVD compared to the general population in both periods. On multivariate analysis, after adjusting for age, sex, race and era of diagnosis, factors associated with reduced odds of CVM were diagnosis of PMF in the RUX era ( HR=0.76; 95% CI: 0.61-0.94, p=0.012), female gender ( HR=0.72; 95% CI: 0.58-0.89, p=0.002) and younger age (&amp;lt;65 years, HR= 0.12; 95% CI: 0.09-0.17, p&amp;lt;0.001. Non-Hispanic Black race was an independent predictor of increased CVM. Conclusion The risk of CVM in PMF compared to the general population did not seem to have increased in the era following the approval of ruxolitinib. The SMRs for overall and some specific cardiovascular diseases appear to be lower in the ruxolitinib era compared to the period before its approval. Lastly, the period following the introduction of ruxolitinib was associated with reduced death from cardiovascular diseases. Hence, ruxolitinib may have had some mortality benefits from cardiovascular disease in PMF; however, further studies are needed to examine and validate this observation.

Therapy-related Acute Myeloid Leukemia in Non-Hodgkin Lymphoma Survivors: Risk, Survival Outcomes and Prognostic Factor Analysis.

Therapy-related acute myeloid leukemia (tAML) is a serious complication in patients with Non-Hodgkin lymphoma (NHL) exposed to chemotherapy or radiation. This extensive database study aims to quantify the risk of tAML in NHL and determine the impact of tAML on the overall survival (OS) of patients with NHL. Patients diagnosed with NHL and de novo AML from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results database. Multiple primary standardized incidence ratio (SIR) sessions of the SEER*Stat software were used to calculate SIR and the absolute excess risk of tAML. Overall survival (OS) was evaluated using Kaplan-Meier curves and compared using log-rank tests. Multivariate analysis was used to study the role of each covariate on OS in patients with tAML. The SIR of tAML was 4.89 (95% CI 4.41-5.41), with a higher incidence of tAML observed for age <60 years, NHL prior to 2013 and within 5 years of diagnosis, and those who received chemotherapy. NHL patients with tAML had lower OS than those without tAML (5-year OS 59% vs. 13%, p < 0.001). Patients with tAML showed worse OS than de novo AML in univariate analysis (5-year OS 13% vs. 25%, p = 0.001) but not in multivariate analysis (HR 0.93, 95% CI 0.82-1.04, p = 0.21). Age ≥60 years and lack of chemotherapy were associated with poor OS in tAML subcategory. Age, time since NHL diagnosis, and receipt of chemotherapy directly influence the risk of development of tAML in NHL survivors.

1638P Risk and prognosis of secondary lung cancer after radiation therapy for thoracic malignancies

Radiation therapy (RT) is a crucial modality for the local control of thoracic cancer (TC), but the effect of pelvic RT on the development of secondary malignancy is still unclear. The aim of this study was to determine the association between exposure to radiotherapy for the treatment of TC and subsequent secondary lung cancer (SLC). The Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for the thoracic cancer. Multiple Cox regression analyses and Fine&Gray competing risk regression were employed to assess the cumulative incidence of SLC. Poisson regression and multiple primary standardized incidence ratios (SIR) were used to evaluate the radiotherapy-associated risk for patients receiving RT. Subgroup analyses of patients stratified by latency time since TC diagnosis, age at TC diagnosis, and calendar year of TC diagnosis stage were also performed. Overall survival and secondary lung cancer -related death were compared among the RT and no radiation therapy (NRT) groups by using Kaplan-Meier analysis and competitive risk analysis. A total of 329,129 observations, 147,847 of whom had been treated with RT, and 6,799 patients developed SLC. Receiving radiotherapy was related to a higher risk of developing SLC for TC patients in multiple Cox regression analyses (adjusted HR, 1.25; 95% CI, 1.19-1.32; P<0.001). The cumulative incidence of developing SLC in TC patients with RT (3.8%) was higher than the cumulative incidence (2.9%) in TC patients with NRT (P=0.012). The results of the dynamic SIR and Poisson regression analysis for SLC revealed that a slightly increased risk of SLC was observed after RT in the late-stage latency and was significantly associated to the variations of age at TC diagnosis. The 10-year OS among SLC patients after RT were comparable to SLC patients after NRT in different site of TC. Radiotherapy for thoracic cancer was associated with higher risks of developing secondary lung cancer compared with patients unexposed to radiotherapy.

Risk and prognosis of secondary bladder cancer after radiation therapy for pelvic cancer.

BackgroundRadiation therapy (RT) is a crucial modality for the local control of pelvic cancer (PC), but the effect of pelvic RT on the development of secondary malignancy is still unclear. This study aimed to identify the relationship between radiation therapy received for the treatment of primary PC and subsequent secondary bladder cancer (SBC).MethodsThe Surveillance, Epidemiology, and End Results (SEER) database (from 1975 to 2015) was queried for PC. Fine-gray competing risk regression and Cox regression analyses were employed to assess the cumulative incidence of SBC. Poisson regression and multiple primary standardized incidence ratios (SIR) were used to evaluate the radiotherapy-associated risk for patients receiving RT. Subgroup analyses of patients stratified by latency time since PC diagnosis, calendar year of PC diagnosis stage, and age at PC diagnosis were also performed. Overall survival (OS) was compared among different treatment groups with SBC by Kaplan–Meier analysis.ResultsA total of 318,165 observations showed that the primary cancers were located in pelvic cavity, 256,313 patients did not receive radiation therapy (NRT), 51,347 patients who underwent external beam radiation therapy (EBRT), and 10,505 patients receiving a combination of EBRT and brachytherapy (EBRT–BRT) who developed SBC. Receiving two types of radiotherapy was strongly consistent with a higher risk of developing SBC for PC patients in Fine-Gray competing risk regression (NRT vs. EBRT, adjusted HR= 1.71, 95% CI: 1.54-1.90, P<0.001; NRT vs. EBRT–BRT, adjusted HR= 2.16, 95% CI: 1.78-2.63, P<0.001). The results of the dynamic SIR and Poisson regression analysis for SBC revealed that a slightly increased risk of SBC was observed after RT in the early latency and was significantly related to the variations of age at PC diagnosis and decreased with time progress. For OS, the SBC after NRT, SBC after EBRT, and SBC after EBRT-BRT of 10-year survival rates were 37.9%, 29.2%, and 22.2%, respectively.ConclusionRadiotherapy for primary PC was associated with higher risks of developing SBC than patients unexposed to radiotherapy. Different pelvic RT treatment modalities had different effects on the risk of SBC.

Risk of second primary malignancy in patients with primary myelofibrosis: A SEER database study.

e19079 Background: Primary myelofibrosis (PMF) carries a poorer prognosis compared to other BCR-ABL-negative myeloproliferative diseases (MPD), and there is increased risk of early mortality due to blast transformation, thrombosis, bleeding complications, and progression of disease. Prior studies report greater incidence of second primary malignancy (SPM) among MPD patients, although the true risk in PMF has not been elucidated. We performed a large database study to evaluate the risk of SPM in PMF patients and analyzed the effects of sociodemographic factors on the risk of SPM. Methods: We used the Surveillance, Epidemiology, and End Results (SEER) database to identify all patients with a histologic diagnosis of PMF from 2009 to 2018. SPM was defined as any subsequent malignancy that developed at least 1 year after the diagnosis of PMF. Using multiple primary standardized incidence ratio (SIR) session of the SEER*Stat software (version 8.3.9), we calculated SIR and absolute excess risk (AER) of SPM for the entire cohort of PMF and also stratified based on age, sex, race, marital status, receipt of chemotherapy, follow-up duration, and year of diagnosis. We generated the 95% confidence intervals (CI) and p-values assuming Poisson distribution of the observed incidences of SPM. Results: A total of 5,273 patients with PMF were included in the analysis, of which 342 patients (6.4%) developed SPM. SPM occurred at SIR of 1.97 (95% CI 1.77-2.18, p&lt;0.05) and AER of 151.87 per 10,000 population. A significantly higher incidence of melanoma (SIR 1.96, 95% CI 1.14-3.14, p&lt;0.05), lymphoma (SIR 3.45, 95% CI 2.31-4.96, p&lt;0.05), and leukemia (SIR 26.87, 95% CI 22.69-31.59, p&lt;0.05) was observed. There was no statistically significant difference in SIR based on sex, race, marital status, follow-up duration, and receipt of chemotherapy. The risk was significantly higher in patients ≤60 years vs patients &gt;60 years (SIR 2.34, 95% CI 1.89-2.86 vs SIR 1.86, 95% CI 1.65-2.10, p 0.01) and for PMF diagnosed after 2009 vs ≤2009 (SIR 2.64, 95% CI 2.26-3.07 vs SIR 1.61, 95% CI 1.40-1.85, p&lt;0.001). Conclusions: Patients with PMF are at a high risk of developing SPM, especially leukemia and lymphoma. Data suggests higher incidence of SPM in patients aged ≤60 years and in the decade after 2009. The impact of ruxolitinib, which was approved in 2011, on the incidence of SPM deserves further study. [Table: see text]

Risk, overall survival, and prognostic analysis of therapy-related acute myeloid leukemia in non-Hodgkin lymphoma survivors.

e19037 Background: Therapy-related acute myeloid leukemia (tAML) is a serious complication in patients with Non-Hodgkin lymphoma (NHL) exposed to chemotherapy or radiation. tAML demonstrates high risk characteristics and poorer outcomes compared with de novo AML. We aimed to quantify the risk of tAML in NHL, determine factors associated with overall survival (OS) in tAML, and compare them with de novo AML. Methods: Patients with a histologic diagnosis of NHL and de novo AML from 2009 to 2018 were identified from the Surveillance, Epidemiology, and End Results (SEER) 18 database. AML that developed at least 1 year after the diagnosis of NHL was classified as tAML. Multiple primary standardized incidence ratio (SIR) sessions of the SEER*Stat software (version 8.3.9) were used to calculate SIR and absolute excess risk (AER) of tAML based on - age, sex, race, year of diagnosis, chemotherapy, radiotherapy, and interval from NHL diagnosis. The 95% confidence intervals (CI) and p-values were generated using multivariate Poisson regression model. OS of both tAML and de novo AML was assessed using Kaplan Meier curves and then compared using log rank test. The roles of various factors on OS in tAML and de novo AML were evaluated using multivariate cox proportional hazard regression. Results: A total of 373 patients with tAML (N for NHL = 301,903) and 23,360 patients with de novo AML were included in the analysis. More de novo AML cases were ≥70 years compared to tAML (41.1% vs 32.7%, p &lt; 0.001). The risk of development of tAML was significantly higher in ages &lt; 60 years compared to 60-69 years and ≥70 years (SIR 14.0, 95% confidence interval [CI] 11.79-16.51 vs SIR 4.87, 95% CI 4.00-5.86 vs SIR 2.80, 95% CI 2.32-3.34, p &lt; 0.0001). Patients who received chemotherapy were more likely to develop tAML than the non- recipients (SIR 8.44, 95% CI 7.51-9.44 vs SIR 1.75, 95% CI 1.37-2.21, p &lt; 0.0001). The risk of tAML was higher within 5 years of NHL diagnosis (SIR 5.05, 95% CI 4.49-5.67 vs SIR 4.39, 95% CI 3.49-5.45, p &lt; 0.001). There was no statistically significant difference in SIR based on sex, race, receipt of radiotherapy, and year of diagnosis. The median OS and 5-year OS were- 8 months and 13.1% for tAML and 10 months and 27.6% for de novo AML. On multivariate analysis, tAML was not found to be an independent predictor of OS (HR 0.93, 95% CI 0.82-1.04, p = 0.21). Age ≥60 years (age 60-69 years: HR 1.53, 95% CI 1.08-2.15, p = 0.01, age ≥70 years: HR 1.93, 95% CI 1.40-2.66, p &lt; 0.001) and no chemotherapy (HR 1.82, 95% CI 1.40-2.35, p &lt; 0.001) were associated with poor OS in tAML subcategory. Conclusions: Our large population-based study shows increased risk of tAML within the first 5 years of NHL diagnosis, younger NHL survivors, and chemotherapy recipients. Older age and no chemotherapy predispose to dismal OS in tAML.

Second primary malignancy in stage I and II breast cancer survivor: A United States population-based study.

e12579 Background: In United States, breast cancer accounts for over 260,000 cases each year and is responsible for over 40,000 deaths. Survival primarily depends on the stage at time of diagnosis. 5-year survival among early breast cancer is more than 50%. It is known that patients with cancer undergoing treatment have a significant risk of developing a second primary malignancy (SPM); we aimed to focus our study at the incidence of various SPM among patients surviving stage I and II breast cancer, which can help in their targeted surveillance. Methods: We utilized Surveillance, Epidemiology, and End Results (SEER) database of the National Cancer Institute to select adult patients (18 and above) diagnosed with stage I and II breast cancer as their first malignancy between January 2000 and December 2015. This is one of the largest cancer registries worldwide. SPM is metachronous cancer which develops six months after an index localized breast cancer diagnosis based on Warren and Gates criteria. Multiple primary standardized incidence ratios (MP-SIR) and absolute excess risk (AER) for an occurrence of SPM were obtained utilizing SEER. SIR is observed to expected incidence ratio (O/E) of SPM and AER, it is an actual number of excess SPMs in patients with early breast cancer per 10,000 person-years at risk. Statistical significance was defined as a p-value ≤ 0.05. Results: We localized 513,408 patients with a diagnosis of stage I and II breast cancer from 2000 - 2015. Patients were followed for a median duration of 8.92 years (range 0.5 to 15.92). Of these patients, 81.5% were white. About 8.6% (43938) of patients developed 47708 primary malignancies. These malignancies were significantly higher than the general population with O/E ratio of 1.15 and AER of 17.12. The median age of diagnosis of SPM was 69.8 years (range 22.8 – 105.08 years). The average latency to develop SPM was 5.28 years (range 0.5 – 15.92 years). Among solid tumors, a statistically significant increased risk was observed with salivary gland, tongue, gastric, colon, lung cancer, and genitourinary cancers. Among hematological malignancies, statistically significant risk was seen for ALL, AML and CML. The risk of hepatobiliary, CNS cancers and lymphoma were significantly lower among our cohort included in current study. The SPM was found significantly increased after the latency of 24 months, and the risk of SPM was greater across all age groups. Conclusions: Due to robust breast cancer screening strategies, a significantly higher proportion of the patients are diagnosed early in the course of the disease which tends to be curative and this group of patients has better survival rates. Our study recognizes that the risk of certain SPM is higher in stage I and II breast cancer survivals compared to general population; and they would benefit from guidelines that can identify cancer with increased risk in these patients population.

MP42-16 VARIOUS INCIDENCE RISKS OF SUBSEQUENT MALIGNANCIES IN URINARY TRACT AFTER INITIAL BLADDER CANCER DIAGNOSIS STRATIFIED BY LATENCIES

You have accessJournal of UrologyCME1 May 2022MP42-16 VARIOUS INCIDENCE RISKS OF SUBSEQUENT MALIGNANCIES IN URINARY TRACT AFTER INITIAL BLADDER CANCER DIAGNOSIS STRATIFIED BY LATENCIES Shu Wang, Ryan Russell, Michael Phelan, and M. Minhaj Siddiqui Shu WangShu Wang More articles by this author , Ryan RussellRyan Russell More articles by this author , Michael PhelanMichael Phelan More articles by this author , and M. Minhaj SiddiquiM. Minhaj Siddiqui More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002608.16AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Urinary tract malignancies after bladder cancer (BCa) diagnosis are uncommon, with reported rates of 1.3-13.7%. Early diagnosis and management during follow-up after the initial BCa event are critical. In this study, we aim to capture the incidence risks of subsequent malignancies (SMs) in the urinary tract after BCa diagnosis and investigate the magnitudes stratified by latencies to the development of SMs. METHODS: The Multiple Primary-Standardized Incidence Ratios (MP-SIR) session with SEER Research Plus data was used to search patients diagnosed with BCa as the first primary malignancy between 1975 to 2018. Patients who developed malignancies in the urinary tract at least 3 months after the diagnosis of BCa were considered “SMs”. The relative risks (RRs) of SMs were calculated by the number of observed events/number of expected events (based on U.S. mortality rates) and presented as mean+/-95%CI. RESULTS: 858 patients were identified, 78% (669/858) of which were males. The mean age of Bca diagnosis in this study cohort was 69.46 years, and mean latencies to the development of SMs in the renal pelvis, ureter, and other urinary organs (including urethra, paraurethral glands, and overlapping lesion of urinary organs) were 4.1 years, 3.81 years, and 4.9 years, respectively. The overall RRs of SMs in renal pelvis, ureter, and other urinary organs were 11.02 (95%CI 9.93-12.21), 16.44 (95%CI 14.82-18.18), and 9.95 (95%CI 8.41-11.69), respectively (all p<0.05). We calculated the RR ratios of (1-3years):(3-5years):(5+years) to compare RRs stratified by latencies to the development of SMs. RR ratios were 2.07:1.18:1, 1.24:1.30:1, and 2.59:2.42:1 for renal pelvis, ureter, and other urinary organs, respectively (Figure 1). The RR of SMs dropped dramatically 3 years afterward in the renal pelvis, 5 years in other urinary organs, and stayed high even after 5 years in ureter. CONCLUSIONS: Following the initial diagnosis of BCa, the RRs of SMs vary in different urinary organs when stratified by latencies. This information could be used for follow-up strategy after initial BCa diagnosis and treatment. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e738 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shu Wang More articles by this author Ryan Russell More articles by this author Michael Phelan More articles by this author M. Minhaj Siddiqui More articles by this author Expand All Advertisement PDF DownloadLoading ...

Characterization of Second Primary Malignancies in Mucosa-Associated Lymphoid Tissue Lymphomas: A SEER Database Interrogation.

Introduction: Second primary malignancies (SPMs) are long-term complications in cancer survivors. Mucosa-associated lymphoid tissue (MALT) lymphomas are indolent extra-nodal marginal zone lymphomas, the majority of which typically have long-term survival. In this study, we investigated the incidence and pattern of SPMs in adult patients diagnosed with MALT lymphomas between January 2000 and December 2016. Methods: Using the SEER-18 database and multiple primary standardized incidence ratio (MP-SIR) session of SEER stat software for statistical analysis, we assessed SPMs in MALT lymphomas. Results: During this time, a total of 12,500 cases of MALT lymphomas were diagnosed, of which 1466 patients developed 1626 SPMs (O/E ratio: 1.48, 95% CI:1.41-1.55, P<.001). The median latency period for development of SPMs was 54 months (range 6-201 months). Secondary non-Hodgkin lymphomas, as defined by SEER as distinct from the primary lymphoma, was the most common SPM with 299 cases, followed by lung cancer (O/E ratio: 6.15, 95% CI:5.47-6.89, P<.0001). There were 898 SPMs that developed between 6- 59 months (O/E ratio: 1.47, 95% CI:1.37-1.57, P<.0001) and 728 after 60 months latency (O/E ratio: 1.5, 95% CI:1.39-1.61, P<.0001) after diagnosis of the primary MALT lymphomas. An increased incidence of both solid and hematologic cancers occurred in patients as early as 6 months after diagnosis of MALT lymphoma. Conclusion: These findings indicate that despite the indolent nature of most MALT lymphomas, there is an increased risk for SPMs warranting long-term follow up.

Cancer patterns in nasopharyngeal carcinoma multiplex families over 15 years.

Genetic and environmental factors are important determinants of nasopharyngeal carcinoma (NPC). NPC is associated with Epstein-Barr virus (EBV) infection. Studies have reported familial aggregation of NPC, but evidence has been mixed for elevated rates of cancers other than NPC. The authors reassessed their previous evaluation of familial aggregation of cancer in 348 high-risk Taiwanese multiplex families with 2 or more NPC cases enrolled between 1980 and 2003. Participants were linked to the Taiwan National Cancer Registry and National Death Registry to identify cancers. In all, 2590 individuals contributed 37,959 person-years over an average of 15 years of follow-up; 314 incident cancers were identified. The authors computed multiple primary standardized incidence ratios (MP-SIRs) to evaluate the overall risk and the risk of infection-associated, EBV-associated, and individual cancers. The overall MP-SIR was 1.24 (95% confidence interval [CI], 1.10-1.38). The exclusion of excess NPC risk led to an overall MP-SIR of 1.11 (95% CI, 0.98-1.25). Similarly, the risk of cancers associated with infectious agents was driven by the excess in NPC, and its exclusion led to an MP-SIR of 1.22 (95% CI, 0.99-1.48) for infection-associated cancers and to an MP-SIR of 1.18 (95% CI, 0.72-1.82) for EBV-associated cancers. The authors observed a significant excess of second cancers among NPC cases (oral cancer, mouth cancer, tongue cancer, gum cancer, nasal cavity cancer, bone cancer, and non-Hodgkin lymphoma). This reassessment of the largest NPC multiplex family study confirms the presence of NPC coaggregation within families in Taiwan but does not provide evidence for a broader familial syndrome involving NPC and other tumors. Among NPC cases, elevated rates of secondary cancers, mostly at the, head and neck and hematopoietic cancers suggest radiation treatment effects on subsequent cancer risk.

Risk and Outcomes of Second Malignant Neoplasms in Chronic Myeloid Leukemia Survivors

BACKGROUND: The introduction of tyrosine kinase inhibitors (TKIs) has significantly improved the long term survival of patients with chronic myeloid leukemia (CML). Patients in cytogenetic remission have life expectancy that approaches that of the general population. The majority of patients with CML remain on TKIs indefinitely. It is unclear whether prolonged exposure to TKIs increases the risk of second malignant neoplasms (SMN) and if malignancies developing in CML survivors harbor similar prognosis to malignancies in non-CML patients. METHODS: We utilized the Surveillance, Epidemiology and End Results 18 (SEER 18) registries to evaluate SMN in adult patients diagnosed with BCR-ABL1 positive CML as first malignant neoplasm between 2001 (introduction of TKIs) and 2014(most recent year with available data). Follow up is current to the end of 2014 (November 2016 submission). Using the multiple primary standardized incidence ratio (SIR) session of the SEER*stat software (version 8.1.5), we calculated the SIR of SMNs for CML survivors. Cases diagnosed at autopsy and by death certificate only were excluded. SMN was defined as a metachronous non-leukemia malignancy that developed at least 6 months after the diagnosis of CML. Survival rates for the most common malignancies in CML survivors were compared with tumor site, age, gender, race/ethnicity, histology, grade and stage-matched cases developing in individuals without a prior diagnosis of CML. RESULTS: There were 3,407 patients included in the analysis with a median follow up of 41 months. The median age at diagnoses was 53 years (range 20-98) and 56% were men. Of these patients, 170 (4.99%) developed a SMN after a median of 36.5 months from diagnosis of CML (range 6-160) with a SIR of 1.40 (95%C.I. 1.19-1.62) and excess risk of 34.92 per 10,000 persons* year. The most commonly occurring SMNs were lung (n=30), prostate (n=28) and colorectal (n=19). A significantly increased risk was noted for cancers of the respiratory tract (n=32, SIR 1.69, 95%C.I. 1.15-2.4), genitourinary (GU) tract (n=54, SIR 1.39, 95%C.I. 1.04-1.81) and skin excluding basal cell and squamous cell carcinoma (n=13, SIR 1.94, 95%C.I. 1.04-3.32). There was no significant increase in risk of gastrointestinal (GI) tract (n=32, SIR 1.36, 95%C.I. 0.93-1.92), head and neck (n=5, SIR 1.51, 95%C.I. 0.49-3.52) and breast cancer (n=13, SIR 0.85, 95%C.I. 0.45-1.46). Using 3:1 matching (3 de novo malignancies to 1 post-CML SMN case), we compared survival data for cancers of the respiratory, GU and GI tract. Patients with GU malignancies developing after CML had worse overall survival than matched patients without prior CML diagnosis (P=0.018). There was no survival difference between post-CML and non-post-CML patients with respiratory or GI malignancies (Figure). CONCLUSION: CML survivors have an increased risk of developing subsequent malignancies as compared to the general population. The increase in risk is more evident for GU, respiratory and non-basal cell, non-squamous cell carcinoma skin cancer. GU malignancies in CML survivors have worse outcomes than in non-CML patients. Future investigation should focus on the biologic mechanism of increased susceptibility of CML survivors to solid tumors. Download : Download high-res image (60KB) Download : Download full-size image Figure . Disclosures No relevant conflicts of interest to declare.

Risk of Mortality and Leukemic Transformation in Primary Myelofibrosis before and after Ruxolitinib Approval

Background: Primary myelofibrosis (PMF) has the worst prognosis of the classical BCR-ABL1 negative myeloproliferative neoplasms, with a median overall survival of six years. Factors affecting survival include age, symptom burden, cytopenias, mutation profile, and development of second malignancies including transformation to acute myeloid leukemia (AML). Ruxolitinib, a selective JAK1 and JAK2 inhibitor, was granted approval by the United States (US) Food and Drug Administration for treatment of intermediate and high-risk PMF in November 2011 based on reduction in spleen volume and demonstration of symptom improvement. The impact of ruxolitinib on PMF survival is unknown. In this study, we aimed to evaluate whether there has been a change in survival and patterns of second primary malignancies (SPMs) including AML transformation among PMF population in US after ruxolitinib approval. Methods: Using the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER)-18 survival and Multiple Primary Standardized Incidence Ratio (MP-SIR) registries, we conducted a retrospective study with patients diagnosed with PMF between the years of 2007 and 2016. We divided these patients into two five-year cohorts, pre-ruxolitinib approval (2007-2011) and post-ruxolitinib approval (2012-2016), and compared relative survival rates (RSRs) and standardized incidence ratios (SIRs) of SPMs between the cohorts. SIRs were calculated as the ratio of observed to expected malignancy cases over the specified time periods. Median follow-up duration was five years for each cohort. RSRs and SIRs were compared between cohorts using two-proportion Z-tests. Results: We included 2164 patients diagnosed with PMF between 2007 and 2016 with data available in the SEER-18 survival and MP-SIR registries. Of these, 1051 (49%) patients were included in the pre-ruxolitinib cohort and 1113 (51%) patients were included in the post-ruxolitinib cohort. There was no significant difference in the four-year RSRs between the pre-ruxolitinib and post-ruxolitinib cohorts (55% vs. 56%, p = 0.719). A higher proportion of SPMs occurred in the post-ruxolitinib cohort when compared with the pre-ruxolitinib cohort (60% vs. 40%, p &amp;lt; 0.001). Hematologic malignancies comprised a majority of all SPMs (AML 39% and non-Hodgkin lymphoma 16%). A higher incidence of AML transformation occurred in the post-ruxolitinib cohort when compared with the pre-ruxolitinib cohort (SIR 121.48 vs. 72.22, p = 0.037). Non-hematologic malignancies were also more common in the post-ruxolitinib cohort when compared with the pre-ruxolitinib cohort (SIR 1.09 vs. 0.94, p &amp;lt; 0.001). The most common non-hematologic malignancies were cancers of the respiratory tract, urinary tract, and prostate gland, though their SIRs were not significant in either cohort. Conclusions: Our study results suggest that despite improvements in prognostication and the approval of ruxolitinib, the prognosis of PMF remains poor in the US. These results may be due to low uptake of ruxolitinib in practice or a lack of benefit from the drug itself. Additionally, for reasons that are unclear, SPM incidence has increased in the five years following the approval of this drug. Further studies should be conducted to determine the cause of these findings. Figure Disclosures Shah: Dren Bio: Consultancy. Vachhani:astellas: Speakers Bureau; agios, blueprint medicines, jazz pharmaceuticals, daiichi sankyo: Membership on an entity's Board of Directors or advisory committees; incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; abbvie: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

Risk and Prognosis of Secondary Rectal Cancer After Radiation Therapy for Pelvic Cancer.

BackgroundThe relationship between pelvic radiation therapy (RT) and second primary rectal cancer (SPRC) is unclear. The aim of this study was to assess the risk and prognosis of SPRC after pelvic RT.Materials and MethodsData for patients who had primary pelvic cancer (PPC) between 1973 and 2016 were retrieved from the Surveillance, Epidemiology, and End Results (SEER) database. Multiple primary standardized incidence ratios (SIRs) were used to assess the risk of SPRC. Five-year overall survival (OS) and rectal cancer-specific survival (RCSS) were calculated using Kaplan–Meier curves.ResultsA total of 573,306 PPC patients were included, 141,225 of whom had been treated with RT. Primary cancers were located in the prostate (50.83%), bladder (24.18%), corpus uterus (16.26%), cervix (5.83%), and ovary (2.91%). A total of 1,491 patients developed SPRC. Overall, the patients who received RT were at increased risk of developing SPRC (SIR = 1.39, 95% confidence interval [CI]: 1.27–1.52). The risk of SPRC decreased in patients who did not undergo RT (SIR = 0.85, 95% CI: 0.80–0.91). The SIR for SPRC in patients who underwent external beam radiation therapy (EBRT) was 1.22 (95% CI: 1.09–1.36). The SIR for SPRC in patients who underwent a combination of EBRT and brachytherapy (EBRT–BRT) was 1.85 (95% CI: 1.60–2.14). For patients who received RT, the SIR for SPRC increased with time after a 5-year latency period from PPC diagnosis. The survival of RT-treated SPRC patients was significantly worse than that of patients with primary rectal cancer only (PRCO).ConclusionsPatients receiving pelvic RT were at an increased risk of developing SPRC. Different pelvic RT treatment modalities had different effects on the risk of SPRC. We suggest that long-term surveillance of SPRC risk is required for patients who have undergone pelvic RT, especially young patients.

The Risk of Second Primary Malignancies in Patients With Lung Neuroendocrine Tumors: A Population-Based Study on SEER Database

PurposeWe investigated the at-risk sites of second primary malignancies (SPMs) and evaluate the risk factors of SPMs among lung neuroendocrine tumors (LNETs) survivors by using the surveillance, epidemiology, and end results (SEER) database. MethodsPropensity-score matching was performed to conduct a case-control study from the surveillance, epidemiology, and end results (SEER) database. Cox regression analysis and multiple primary standardized incidence ratios were performed to investigate the risk factors of occurrence of SPMs among patients with LNETs. ResultsOf 3,206 patients with LNETs after matching, 539 developed SPMs. The risk of developing SPMs was higher in older patients (55–74 vs ≦54: hazard ratios [HR] 1.875; age ≧75 vs ≦54: HR 2.713), higher-stage of LNETs (regional vs localized: HR 1.387; distant vs localized: HR 2.732) and recent periods of diagnosis (2004–2014 vs 1984–1993: HR 1.735). Patients with SCLC, TC and LENEC had a higher risk for SPMs compared to general population. Lung and bronchus, larynx and some digestive organs had higher risk for SPMs while some sex hormone related organs like prostate, breast, and female reproductive system had a lower incidence of SPMs. ConclusionsPatients with LNETs had overall higher risks of SPMs than general population. Different types of second primary malignancies occurred in different periods after LNETs were diagnosed. Further investigations are required to screen different second primary malignancies for those with primary LNETs.

Incidence of second primary malignancy (SPM) in patients with mucosa-associated lymphoid tissue lymphoma (MALToma).

e20043 Background: MALTomas are extranodal marginal zone lymphomas that arise from B cells in various mucosal lymphoid tissue and are typically indolent. Patients with MALTomas may be at risk for additional cancers due to their long-term survival following treatment, however the incidence of SPM in MALTomas in the U.S. has not been previously described. Methods: Adults with MALT lymphoma were identified using the 2000-2016 SEER-18 database. SPM was defined as tumors diagnosed ≥6 months and up to x months from lymphoma diagnosis. SEER*stat was used to calculate SPM by multiple primary standardized incidence ratio based on observed (O) and expected (E) cases. The expected cases of new cancers of specific types were estimated by assuming that incidence rates for new primary tumors corresponded to sex, age, and calendar time–specific SEER rates for similar invasive primary cancers and applying those rates to the accumulated person-years (PYR) of observation. Excess absolute risk (EAR) of malignancy per 10,000 PYR at risk was calculated as ([O − E]/PYR) × 10,000. Results: As summarized in the table, 12,500 patients were diagnosed with MALT lymphoma of which 1466 (11.8%) developed 1626 SPMs (O/E rate 1.5, 95%CI 1.4-1.5, P &lt; 0.001, EAR 70.4). Median latency period was 54 months (range 6 - 201). Non-Hodgkin lymphomas at separate tissue sites were the most common SPM, with 299 documented cases (O/E rate 6.2, 95%CI -5.4-6.8, P &lt; 0.001, EAR 33.4). Between 6-24 months from MALToma diagnosis, head and neck, renal cell, liver, and anal cancers were increased, while after 24 months, gastric and small bowel cancers, CLL, ALL, and myeloma were increased compared to the general population of the same age group. Conclusions: There is distinct pattern of SPM among patients with MALT lymphoma in within and after 2 years from diagnosis, with an increased incidence compared to the general population. Consider the median latency, SPM may be due in part to the long-term survival and relatively older age of this population. [Table: see text]

Impact of immune checkpoint and BRAF inhibitors on the incidence of second primary malignancies (SPM) in melanoma.

12061 Background: Prior studies have shown an increased risk of SPM in melanoma, however there is limited data on the incidence of SPM following the 2011 approvals of immune checkpoint (ipilimumab) and BRAF (vemurafenib) inhibitors, which have become standard of care. We present data comparing SPM rates before and after introduction of these agents for advanced cutaneous melanoma. Methods: Adult melanoma patients with regional or distant metastases were identified from SEER-18 database and divided into cohorts: 2005-2010 and 2011-2016. SPM was defined as tumors diagnosed ≥6 months from diagnosis of the primary cancer. SEER*stat was used to calculate SPM by multiple primary standardized incidence ratio based on observed (O) and expected (E) cases. The expected numbers of new cancers of specific types were estimated by assuming that incidence rates for new primary tumors corresponded to sex, age, and calendar time–specific SEER rates for similar invasive primary cancers and applying those rates to the accumulated person-years (PYR) of observation. Excess absolute risk (EAR) of malignancy per 10,000 PYR at risk was calculated as ([O − E]/PYR) × 10,000. Results: As shown in the table, from before 2005-2010, 421 of 7991 patients (5.2%) with advanced melanoma had 444 SPM (O/E ratio 2.2, 95% CI 1.9-2.4, P &lt; 0.0001, EAR 157). In comparison, from 2011-2016, 527 of 9341 patients (5.6%) developed 584 SPM (O/E ratio 2.5, 95% CI 2.3-2.7, P &lt; 0.0001, EAR 193). Incidence of AML, myeloma, and pancreatic cancer increased in 2005-2010, while soft tissue malignancies increased from 2011-2016. The incidence of thyroid, brain, and small bowel tumors increased in both groups from 2005-2016. Conclusions: There is a distinct pattern as well as increased latency of SPM in patients with advanced melanoma in the era of immune checkpoint and BRAF inhibitors. We speculate that reduction in chemotherapy use, augmentation of immunosurveillance, and inhibition of oncogenic pathways may impact the pathogenesis of SPM. [Table: see text]

Characteristics and survival of secondary male breast cancer: SEER database analysis.

e13690 Background: Male breast cancer (MBC) is rare accounting for less than 0.5% of all cancer diagnoses in men. We used the term secondary male breast cancer (sMBC) to refer to ipsilateral and contralateral recurrences in addition to new primary MBC. Given its low incidence, data regarding the risk of developing sMBC and its characteristics are scarce. Methods: Multiple Primary Standardized Incidence Ratios (MP-SIR) session was conducted from the SEER*Stat software. We included all patients diagnosed with stage I,II and III MBC between 1990 to 2015 from the Surveillance Epidemiology and End Results (SEER) 18 registry. The standardized incidence ratio (SIR) was calculated as an estimate of the risk of a second primary malignancy based on the incidence in the general population. Descriptive statistics and Kaplan-Meier analysis were performed using SPSS software. Results: Among all 2321 men diagnosed with a first primary MBC during the study period, 28 patients had a subsequent diagnosis of MBC. The risk of sMBC was significantly elevated with SIR of 33.12 (95% CI, 22.18 – 47.56). The median latency period between the initial and subsequent diagnoses was 5.9 years. 82.1% of the patients were White, 14.3% Black and 3.6% Asian/Pacific Islander. Majority of the cases constituting 85.7% of sMBC were diagnosed in the contralateral breast. 67.8% of the sMBC remained hormone receptors status positive similar to the initial status of the primary diagnosis. 42.9% of the sMBC patients were diagnosed with stage I, 17.9% with stage II, 3.6% with stage III, 17.9% with stage IV and 17.9% of unknown stage. The median overall survival for sMBC was 96 months (95% CI, 11.3-180.6). We also found an increased risk of developing liver cancer (SIR: 2.16), prostate cancer (SIR: 1.29), thyroid cancer (SIR: 3.08) and acute myeloid leukemia (SIR: 2.4) in individuals after a diagnosis of MBC. Conclusions: Men diagnosed with breast cancer are at increased risk of sMBC in addition to other malignancies which require careful monitoring after completing initial treatment. Contralateral mammogram screening or prophylactic contralateral mastectomy can be considered based on patient’s preferences and values.

Myelodysplastic syndrome survival and secondary AML trends in the United States.

7552 Background: Myelodysplastic syndrome (MDS) is a rare heterogeneous group of hematologic stem cell disorders. The most recent FDA therapies approved for the treatment of MDS were decitabine (May 2006), lenalidomide (June 2005), and azacitidine (November 2004). This analysis utilized a population-based cancer registry to identify changes in survival rates and secondary AML rates among patients with MDS. Methods: SEER 18 regions database (November 2017 submission) was accessed to obtain data on survival and secondary malignancies using SEER*Stat 8.3.6. ICD-O-3 codes were used to identify patients with refractory anemia (RA), refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, refractory cytopenia with multilineage dysplasia, MDS with 5q deletion, therapy-related MDS, and MDS, not otherwise specified. An observed survival analysis was conducted using a cohort diagnosed between 2001 and 2004 and another diagnosed between 2009 and 2012. Secondary AML risk was calculated using multiple primary - standardized incidence ratios (MP-SIR) to obtain observed/expected (O/E) ratio. Results: Three-year observed survival rates for patients diagnosed between 2001 and 2004 was 53.2% (50.4%, 55.9%) and was 61.2% (57.9%, 64.3%) for patients diagnosed between 2009 and 2012. There was no observed survival difference among other MDS subtypes. O/E ratio for development of AML among patients with RA was 2.77 (0.57, 8.11) for patients diagnosed between 2001 and 2004, and 49.49 (33.39, 70.65) for patients diagnosed between 2009 and 2012. Conclusions: Survival among patients diagnosed with RA has improved in recent years, whereas survival among other subtypes of MDS has not changed. Secondary AML rates have increased among RA patients identified in the population-based cancer registry.

Increased Risk of Acute Myelogenous Leukemia After Early Onset but Not Late-Onset Colorectal Cancer.

Early onset colorectal cancer in persons younger than 50 years is increasingly common. Clinical and molecular characterizations reveal a distinctive disease. Thirty percent of patients have mutations of hereditary cancer syndromes, especially Lynch syndrome. A recent analysis, testing germline DNA for mutations in 25 cancer susceptibility genes, showed that some patients younger than 50 years had mutations of high-penetrance colorectal cancer genes such as APC (adenopolyposis coli). Others had mutations in high-penetrance or moderate-penetrance genes not traditionally associated with colorectal cancer, such as ATM (ataxia telangiectasia mutated), whereas still others had low penetrance colorectal cancer genes. In the current study, we examined the incidence of second cancers following early onset (age less than 50 y) colorectal cancer. The initial study population was assembled using records from the Surveillance, Epidemiology, and End Results (SEER) program of the National Cancer Institute. The SEER*Stat MP-SIR (multiple primary-standardized incidence ratio) tool was used to calculate SIRs and excess risk for second primary malignancies. The SIR is expressed as the ratio of observed-to-expected (O/E) cases. We used The Cancer Genome Atlas (TCGA) and AACR Project Genie for genetic analysis. The data were accessed with the online Xena Browser and cBioportal. Acute myelogenous leukemia (AML) O/E ratios were significantly >1 in patients aged less than 50 years, at 12 to 59 months after colorectal cancer. In patients aged 50 years and older, O/E ratios were equal to 1 or quite close at 12 to 59 months after colorectal cancer. Alterations in 3 AML genes, CEBPA-AS1, MLLT1, and MLLT6, affected the prognosis of colorectal cancer patients less than 50 years but not older than 50 years. One AML gene, FLT3, had the highest copy number alteration frequency of any gene in 1438 colorectal patients 18 to 48 years of age. Genetic alterations of FLT3/TP53 were mutually exclusive. Genetic alterations of FLT3/JAK2 and JAK2/CTNNB1 were co-occurrent. These observations suggest that early onset colorectal cancer and AML may be related diseases.