Risk Of Second Primary Malignancies Research Articles

Second Primary Malignancies in Long Term Acute Lymphoblastic Leukemia Survivors of Three Age Groups

Background:Survivors of Acute Lymphoblastic Leukemia (ALL) are at an increased risk of subsequent malignancies secondary to genetic makeup, and exposure to environmental and treatment factors. Younger patients are exposed to different risk factors than older patients, which may result in differences in the risk of second malignancies. Additionally, there is not much information regarding the long term risk of subsequent malignancies. Therefore, we conducted this study to analyze and compare the risks of all second malignancies in patients aged under 15 (pediatric), 15-39 (Adolescent and Young Adult) and over 40 (Adults), five years after their initial diagnosis.Methods:Using data from the Surveillance, Epidemiology and End Results 9 database, Nov 2016 Sub {1973-2012}, we determined the risk of secondary malignancies in long term (five years out from diagnosis) survivors of ALL belonging to three age groups at diagnosis: less than 15, 15 to 39, and 40 and above. For the first cohort, patients younger than 15, there were 5200 patients with 69651 patient years of follow up. For the second age cohort, 15-39, there was a total of 949 patients with 10703 patient years of follow up, and for the third cohort, patients aged 40 and over, there were 365 patients with 2497 patient years of follow up. The risk of second primary malignancies is given as the standardized incidence ratio, which is calculated as such: observed incidence[O]/expected incidence[E]Results:Five years after an ALL diagnosis, patients under the age of 15 are at the highest relative risk of developing any type of second cancer (O/E: 3.58; CI: 2.95-4.30; N=114). Patients between the ages of 15-39 had a significantly fewer number of total cases, but still presented a high relative risk of developing any second malignancy (O/E: 1.59; CI: 1.10-2.22; N=34). Although patients over 40 had more total cases of second cancers than patients between 15-39, the data did not present any statistical significant increased relative risk for developing a second cancer when compared to matched population (O/E: 1.06; CI: 0.76-1.44 ; N=41). Patients under the age of 15 are at the highest risk of developing a second cancer of the salivary gland (O/E: 39.75; CI: 17.16-78.33; N=8). For patients under the age of 15, cancers of the oral cavity and pharynx (O/E: 15.38; CI: 7.37-28.28; N=10), brain, (O/E: 10.98; CI: 6.79-16.78; N=21) and thyroid (O/E: 7.07; CI: 4.70-10.21; N=28) represent the highest number of second cancers. Similarly, patients aged 15 to 39 are also at a high risk of developing a cancer of the salivary gland (O/E: 25.70; CI: 3.11-92.85; N=2). For patients aged 40 and above, cancer of the gum and other mouth has the highest increased risk (O/E: 14.73; CI: 1.78-53.22; N=2), but again there are relatively few patients so we cannot make any accurate estimates for second cancers. This decrease in the total number of patients may be due to an increase in the number of deaths resulting from ALL. In the database analyzed patients over 40 surviving one year, we had a total of 1,287 patients, but the same age cohort 4 more years from initial diagnosis only had 365 patients. Only 28% of patients over 40 survived after 5 years.Conclusion:There are several second malignancies that long term survivors of ALL are at increased risk of developing, even after 5 years from their initial diagnosis. These risks vary by age group, with young patients at substantially higher relative risk compared to their peers. However, unfortunately most adult patients died within the first five years of diagnosis. This information may help physicians effectively monitor survivors of ALL of all ages for any second cancers. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Second Primary Malignancies and Cardiovascular Mortality in Hodgkin disease Survivors — a Surveillance, Epidemiology, and End Results Registry Database Study

BackgroundOver the last few decades there has been significant improvements in survival in patients with Hodgkin disease (HD). But long-term HD survivors, especially those treated with radiation therapy (RT) have an increased risk of second primary malignancy and cardiovascular disease (CVD) related mortality. In this context, we conducted this population based study to analyze trends in CVD related mortality and incidence of lung and thyroid cancer in HD survivors treated with RT.Materials and methodsWe used the Surveillance, Epidemiology, and End Results 9 database to calculate the Standardized Incidence Ratio (SIR) and Excess Absolute Risk (EAR) of lung and thyroid cancer as second primary malignancies in survivors of HD diagnosed between 1973 and 2011, and who were treated with RT. Poisson regression models were used to calculate adjusted incidence of lung and thyroid cancer. We further divided the patients diagnosed with HD during this period into two groups based on if or not they received RT and calculated the mortality due to CVD for each group, by year of diagnosis. Poisson regression models were used to calculate adjusted CVD mortality by year of HD diagnosis for each group. In all three cases, trends in incidence or mortality were evaluated by calculating the Estimated Annual Percentage Change (EAPC) from the regression coefficient for year of diagnosis.ResultsWe identified 11,916 HD cases that received RT from the SEER database, who were followed up for a median duration of 160 months (range - 12 to 480 months). Table 1 provides characteristics of the study population. 319 patients developed lung cancer (SIR of 3.72, 95% CI 3.32 - 4.15; EAR of 13.19 per 10,000 person years at risk) and 86 patients developed thyroid cancer (SIR of 3.67, 95% CI 2.94 - 4.53; EAR of 3.54 per 10,000 person years at risk). Median ages at diagnosis of secondary lung and thyroid cancers were 59 years and 42 years respectively, with median latency periods of 16 years and 17 years respectively. 965 patients among 11,916 patients who received RT died from CVD while the number of CVD deaths was 1,182 among the 12,507 patients who were not administered RT.Using Poisson regression models, we calculated the adjusted incidence of secondary lung cancer and thyroid cancer and the adjusted mortality from CVD, by year of diagnosis. Year of diagnosis, age at diagnosis of HD and latency (time since diagnosis of HD) were the independent variables used in the regression model. Between 1973 and 2011, the adjusted incidence of lung cancer declined at an EAPC of -2.68 (95% CI -13.06 to -3.92) and that of thyroid cancer declined at an EAPC of -3.35 (95% CI -5.73 to -1.00) (Figure 1). Over the same period, CVD mortality per 10,000 person years at risk for patients who received RT declined at an EAPC of -4.34 (95% CI -4.97 to -3.73) and that of patients who did not receive RT declined at an EAPC of -1.92 (95% CI -2.47 to -1.39) (Figure 2).ConclusionWe observed a decline in incidence of lung and thyroid malignancies and CVD mortality in HD survivors over the study period. The decline in CVD mortality over time in patients who received RT was steeper compared to that of patients who did not receive RT. Though our study was limited by the lack of details regarding RT, chemotherapy and comorbidities, these findings are most likely a reflection of recent trends in use of reduced doses and field of RT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Preoperative Short-Course Radiotherapy and Surgery versus Surgery Alone for Patients with Rectal Cancer: A Propensity Score-Matched Analysis at 18-Year Follow-Up.

A significant problem for long-term rectal cancer survivors may be the late toxicity of radiotherapy. It creates the possible risk of developing second primary malignancy and a theoretical decrease in overall survival. This study aimed to assess the influence of short-course preoperative radiotherapy in patients with locally advanced rectal cancer on overall survival, local recurrence rate, and second malignancy at 18-year follow-up. The rectal cancer trial was conducted in a single tertiary center between February 1992 and June 2006. A total of 389 patients with locally advanced rectal cancer (cT2-cT4, cN0/+, cM0) were included in the study. Preoperative radiotherapy was conducted in 148 patients and 241 patients underwent surgery alone. The propensity-matched group consisted of 105 patients operated on after radiotherapy and 105 controls. The number of local recurrences was 7 (6.7%) in the preoperative radiotherapy group and 22 (21%) in the surgery alone group (p = 0.016). The 18-year survival analysis showed no survival benefit in the preoperative radiotherapy group (38% versus 48%, p = 0.107) but improved recurrence-free survival (81% versus 58%, p = 0.001). The preoperative short-course radiotherapy significantly decreases the risk of local recurrence in locally advanced rectal cancer and may improve recurrence-free survival without an increased risk of second primary malignancy.

Childhood Cancer: Occurrence, Treatment and Risk of Second Primary Malignancies

Simple SummaryChildhood cancers are mostly of unknown etiology and represent devastating diagnoses. The clinical benefits of steadily increasing tumor control and survival rates are countered by severe and fatal health consequences from genotoxic therapies in long-term survivors of pediatric cancers. Among them, iatrogenic second primary malignancies represent the heaviest burden for the patient. Therefore, particularly in pediatric tumor patients, the reduction of genotoxic treatments and the use of targeted or immune-based oncologic strategies are of high clinical interest. The knowledge of therapy-associated as well as intrinsic risk factors for late sequelae of antineoplastic treatments including secondary primary malignancies offers the opportunity to adapt oncologic therapies for high-risk patients and to intensify follow-up with intervention strategies and multidisciplinary care.Cancer represents the leading cause of disease-related death and treatment-associated morbidity in children with an increasing trend in recent decades worldwide. Nevertheless, the 5-year survival of childhood cancer patients has been raised impressively to more than 80% during the past decades, primarily attributed to improved diagnostic technologies and multiagent cytotoxic regimens. This strong benefit of more efficient tumor control and prolonged survival is compromised by an increased risk of adverse and fatal late sequelae. Long-term survivors of pediatric tumors are at the utmost risk for non-carcinogenic late effects such as cardiomyopathies, neurotoxicity, or pneumopathies, as well as the development of secondary primary malignancies as the most detrimental consequence of genotoxic chemo- and radiotherapy. Promising approaches to reducing the risk of adverse late effects in childhood cancer survivors include high precision irradiation techniques like proton radiotherapy or non-genotoxic targeted therapies and immune-based treatments. However, to date, these therapies are rarely used to treat pediatric cancer patients and survival rates, as well as incidences of late effects, have changed little over the past two decades in this population. Here we provide an overview of the epidemiology and etiology of childhood cancers, current developments for their treatment, and therapy-related adverse late health consequences with a special focus on second primary malignancies.

Second primary malignancies (SPM) in African American (AA) and white patients with multiple myeloma in the National Veterans Affairs (VA) healthcare system.

10507 Background: In the recent decade, novel therapies have led to significant improvements in overall survival (OS) in symptomatic multiple myeloma (MM). With this increase in OS, there is an increase in the incidence of second primary malignancies (SPM) in patients with MM. This is related to multiple factors; we hypothesize that racial disparities also play a role. There is a paucity of studies with large, high quality datasets evaluating racial disparities in SPMs in MM. Our goal is to explore patterns of incidence of SPMs in US Veterans with MM, focusing on racial disparities. Methods: We conducted a retrospective cohort study based on electronic health record (EHR) and cancer registry data recorded in the VA’s Corporate Data Warehouse (CDW) between January 1, 1999 and January 1, 2018. We compared incidence of SPMs (defined as malignancies occurring after the diagnosis and treatment initiation of MM) using the standardized incidence rate ratio (IRR). Univariate and multivariable analyses were performed, using a Cox model adjusting for age, race, gender, treatment era, smoking status, and stage at MM diagnosis. Results: There were 8467 Veterans (97.4% male) with MM identified with self-reported race: White, 5029 (59.4%); AA, 2178 (25.7%); and other or unknown, 1260 (14.9%). At 7.5 years of follow up, 430 (5.1%) MM patients developed SPM while 8037 did not. 982 had received HSCT (Hematopoietic Stem cell transplant) of whom 65 (6.62%), a significantly higher proportion developed SPM versus those without HSCT (n = 7485) of whom 365 (4.87%) developed SPM (p = 0.024). Among those Veterans who had SPM 380 (88.3%) had solid tumors, 50 (11.6 %) had hematological malignancies. Of 88.3% with solid SPM the distribution was: prostate cancer, 113 (29.7%); digestive tract cancers, 63 (16.6%); lung cancer, 55 (14.4%); and GU (bladder/renal/testicular), 48(12.6%). The cumulative incidence of developing SPM increased steadily over time for the duration of this study period of 7.5 years from diagnosis. The median age of diagnosis for Whites was 68.2 years and for AA was 64.3 years, (p < 0.001) demonstrating that MM occurred earlier in AA. The hazard ratio for AA versus whites to develop SPMs was 1.21 (0.975-1.505) (p = 0.0823). However, the risk of prostate cancer was significantly higher in AA with an adjusted hazard ratio of 1.81 (1.196-2.739) (p = 0.005). No racial disparities were observed in the incidence of other types of SPMs. Conclusions: Our study suggests that the risk of SPMs does not plateau over a patient’s lifetime. HSCT was found to be an independent predictor of SPM, while smoking and agent orange were not. Our cohort is one of the largest groups of AA with MM in published literature. AA did not have a higher incidence of SPMs overall; but had a significantly higher incidence of prostate cancer than whites. We hope to develop an individualized predictive model for SPM in patients with MM.

Malignancies diagnosed before and after anal squamous cell carcinomas: A SEER registry analysis.

BackgroundIncreased risk of a second primary malignancy (SPM) before or after diagnosis of anal squamous cell carcinoma (ASCC) has been reported in a previous single‐institution study. We hypothesize that patients diagnosed with ASCC are at increased risk for developing SPMs before or after the diagnosis of ASCC. The primary objective of this study was to identify the diagnoses of cancer most likely to occur as SPMs before or after ASCC.MethodsThis work employs the Surveillance, Epidemiology, and End Results (SEER) Program registry data to conduct a US‐population‐based study of patients diagnosed with ASCC between 1975 and 2016. In patients diagnosed with ASCC, we evaluated the risk of SPMs and the risk of developing ASCC as an SPM after another cancer using standardized incidence ratios (SIR) for all SPMs by calculating the ratio of observed events in the ASCC cohort compared to expected (O/E) events in a matched reference cohort of the general population.ResultsA total of 7,594 patients with primary ASCC were included. Patients with ASCC were at increased risk of the diagnosis of an SPM (SIR = 1.45), particularly cancers of the lung, vulva, oropharynx, or colon. Patients with ASCC had an increased rate of previous malignancy (SIR = 1.23), especially Kaposi sarcoma or vulvar cancer. Overall elevated incidence of SPMs was unrelated to prior radiation treatment. Radiation treatment was associated with increased risk for SPMs in the female genital system but appeared protective against prostate cancer as SPMs.ConclusionsOur findings support increased surveillance and screening for second malignancies in patients with these diagnoses, as patients with ASCC are often either survivors of a prior cancer diagnosis or are at increased risk of developing later malignancies.

Patients with Early-Onset Colorectal Cancer Have an Increased Risk of Second Primary Malignancy.

While overall colorectal cancer (CRC) rates in the USA are declining, the incidence of early-onset CRC (eoCRC) under age 50 is increasing. The aim of this study was to examine the risk of a second primary malignancy (SPM) in individuals with eoCRC, and how this risk compares to those with late-onset CRC (loCRC). We used data from the Surveillance, Epidemiology, and End Results Program database to examine the risk of SPM after a diagnosis of eoCRC. Standardized incidence ratios (SIR) were used to estimate the risk of SPM after eoCRC and loCRC in comparison with the risk of malignancy in the general population. Compared to the general population, individuals with eoCRC, but not loCRC, had an increased lifetime risk of SPM (SIR 1.42, 95% CI 1.37-1.48 and SIR 1.00, 95% CI 0.99-1.02, respectively), and locations at highest risk were the small intestine, ureter, rectum, and colon. The risk of SPM after eoCRC was similar in men and women, but higher in non-whites compared to whites and higher in those with a lower area-level median household income. The risk of SPM following eoCRC was high in the first 5years after diagnosis (SIR 2.44, 95% CI 2.24-2.66) and, in a birth cohort analysis, was found to be increasing over time. Individuals with eoCRC have a lifetime risk of SPM nearly 50% higher than the general population. The risk of SPM is highest in the first 5years after diagnosis and is increasing over time.

Second primary malignancies after ocular adnexal lymphoma diagnosis

BackgroundAlthough studies have investigated the risk of second primary malignancies (SPMs) associated with lymphoma of various sites, limited studies have investigated this risk in patients with lymphoma originating within the ocular adnexa. We conducted a retrospective study to assess incidence of secondary malignancies in patients with a prior diagnosis of ocular adnexal lymphoma (OAL) and to determine latency periods and age-groups at increased risk for SPM occurrence.MethodsRetrospective analysis was performed on data obtained from Surveillance, Epidemiology, and End Results (SEER) 9 database. Patients with an initial primary malignancy diagnosis of OAL between 1973 and 2015 were included in the study. Standardized incidence ratios (SIR) and excess absolute risks (EAR) compared to a SEER reference population with similar sex, race, age, and calendar year were computed for SPMs. Excess absolute risk is per 10,000 individuals; alpha of 0.05 was used.ResultsOf 1834 patients with primary ocular adnexal lymphoma, 279 developed a secondary malignancy during average follow-up of 110.03 months (+/− 88.46), denoting higher incidence than expected (SIR 1.20; 95% CI, 1.07 to 1.35; EAR 30.56). Amongst the primary lymphoma cohort, 98.7% (1810/1834) of patients had non-Hodgkin’s lymphoma and amongst those that developed secondary malignancies, 99.6% (278/279) had non-Hodgkin’s lymphoma. Patients exhibited increased incidence of lymphohematopoietic and non-lymphohematopoietic second malignancies and no secondary malignancies of the eye or orbit. Patients had increased incidence of secondary malignancies in the first year (SIR 2.07; 95% CI, 1.49 to 2.79; EAR 150.37) and 1–5 years following lymphoma diagnosis (SIR 1.24; 95% CI, 1.01 to 1.51; EAR 34.89). Patients with various OAL subtypes demonstrated differing patterns of site-specific and overall SPM risk.ConclusionsPatients with prior diagnosis of ocular adnexal lymphoma possess increased risk of hematologic and non-hematologic secondary malignancies. Risk of secondary malignancy could vary by lymphoma subtype. Patients with ocular adnexal lymphoma may benefit from regular surveillance to promote early detection of second primary malignancies.

Risk and survival of second primary malignancies following diagnosis of gastric mucosa-associated lymphoid tissue lymphomas: A population-based study

Whether gastric mucosa-associated lymphoid tissue lymphoma (GML) is associated with a higher risk of second primary malignancy (SPM) remains controversial. This study aimed to evaluate the detailed risk of SPM and its prognosis in patients with GML based on a large population-based cohort. The Surveillance, Epidemiology, and End Results database was searched to identify patients who were diagnosed with GML during 2000–2014. The standardized incidence ratio was used to estimate the relative risk of developing SPM. Overall survival was evaluated using the Kaplan-Meier method with the log-rank test, as well as Cox regression analysis. Among 3,379 patients with GML, 416 patients (12.31%) developed SPMs. Compared to the general US population, GML patients had a significantly increased risk of developing SPM (standardized incidence ratio: 1.46, 95% CI: 1.33–1.61). The SPM sites were stomach, lung and bronchus, small intestine, thyroid, mouth, and non-Hodgkin's lymphoma. The risk of developing SPM in GML patients varied according to clinical and demographic characteristics. Patients with younger age (<50 year), chemotherapy use and radiotherapy use had the higher risk of developing SPMs. Relative to patients with only GML, GML patients who developed the SPMs had significantly poorer overall survival (P < 0.001). Among GML patients with SPMs, poor overall survival was independently associated with non-localized SPM disease, shorter latency period (<60 months), chemotherapy use and older age (≥70 year). Patients with GML had an elevated risk of developing SPM, which was associated with a poor prognosis. These findings may be useful for improving follow-up surveillance for patients with GML.

Second primary malignancies in patients with melanoma in situ: Insights from the surveillance, epidemiology, and end results program

BackgroundMelanoma in situ (MIS) is among the most frequently diagnosed cancers in the United States. Emerging data suggest that MIS is associated with an increased risk of developing a second primary malignancy (SPM). ObjectivesTo determine trends in MIS-associated SPMs and identify MIS-specific features that increase SPM risk. MethodsIn this retrospective population-based study, we identified 90,075 patients who were diagnosed with MIS between 1973 and 2015 from the Surveillance, Epidemiology, and End Results database. The risk of developing an SPM among these individuals was compared to individuals without a diagnosis of MIS. The risk of developing an SPM among patients with a diagnosis of MIS was also increased over time. ResultsPatients with a diagnosis of MIS had an increased relative risk (RR) of developing an SPM as compared to the general population with an identical age, sex, race, and follow-up period. The RR of a metachronous malignancy in MIS patients also increased over time, as follows: 1.16 (95 % CI: 1.07–1.26), 1.19 (95 % CI: 1.14–1.23), 1.30 (95 % CI: 1.27–1.33), and 1.52 (95 % CI: 1.49–1.56) in 1973–1982, 1983–1992, 1993–2002, and 2003–2015, respectively (P < 0.05). In addition, there was a direct correlation between the number of MIS lesions and SPM risk; ≥1, ≥2, and ≥3 tumors portended a 1.5–2, 2–3, and 4–5-fold increased risk of developing an SPM, respectively. ConclusionsMIS is associated with an increased risk of developing an SPM and therefore individuals with a history of MIS may benefit from close medical surveillance.

Risk of Second Primary Malignancies Based on the Histological Subtypes of Colorectal Cancer.

Background: Previous studies have revealed an increased risk of second primary malignancies (SPMs) after colorectal cancer (CRC); however, no previous investigation has quantified differences in the risk of SPMs based on the histological subtypes of first primary CRC.Methods: Patients diagnosed with first primary CRC between 2000 and 2011 were identified from the Surveillance, Epidemiology, and End Results cancer registries. The patients were divided into three cohorts: classical adenocarcinoma (CA), mucinous adenocarcinoma (MA), and signet-ring cell carcinoma (SRCC). Standardized incidence ratios were calculated to assess the risk of SPMs among the patients.Results: Overall risk of SPMs was significantly higher among patients with three histological subtypes of CRC than in the general population. The risk of esophagus cancer was significantly increased in SRCC. The risk of small intestine, colon and rectum, and corpus uteri cancers was high in three histological subtypes, with the highest risk observed in SRCC, followed by MA. Increased risks of second stomach, uterus, urinary bladder, kidney, and thyroid cancers were only observed in CA patients, while increased risk of second renal pelvis cancer was limited to MA patients. Furthermore, the high overall risk of SPMs in CA patients persisted regardless of clinicopathological factors. After surgery combined with chemotherapy treatment, CA patients were more prone to developing second small intestine, colon and rectum cancers than those treated with surgery only. A lower second prostate cancer risk was observed in rectal CA patients treated with surgery combined with radiotherapy than in patients treated with surgery only.Conclusion: The present study revealed that the risk of developing SPMs after CRC varied based on the histological subtypes of the first primary CRC. Although the mechanisms underlying the observed patterns of SPM risk remain unknown, the study provided insights into future cancer surveillance based on the histological subtypes of CRC.

Risk of Second Primary Malignancies among Patients with Early Gastric Cancer Exposed to Recurrent Computed Tomography Scans.

Simple SummaryCancer risk after radiation exposure during childhood has been extensively documented in the literature, although cancer risk associated with recurrent computed tomography (CT) scans during adulthood is less understood. We found a significant relationship between the frequency of CT scans and the subsequent incidence of secondary primary malignancies in patients who have undergone curative resection for early gastric cancer (EGC). On the basis of the low incidence of extragastric recurrence and the risk of radiation exposure, we suggest that overzealous CT surveillance should be avoided in adult patients with EGC.Although computed tomography (CT) scans are very useful for identification or surveillance of malignancy, they are also associated with the risk of cancer caused by ionizing radiation. We investigated the risk of second primary malignancies (SPMs) after frequent abdominopelvic CT scans in a cohort of Korean patients with early gastric cancer (EGC). We performed a cohort study of 11,072 patients who underwent resection for EGC at Samsung Medical Center and validated the results using data from 7908 patients in a Korean National Health Insurance Service cohort. Cox proportional hazards regression model was used to estimate hazard ratios (HRs) for intra-abdominal SPM. During 43,766.5 person-years of the follow-up at our center, 322 patients developed intra-abdominal SPMs. Patients who underwent receiving >8 abdominopelvic CT scans had a significantly greater risk of developing SPM (HR, 2.73; 95% CI, 1.66–4.50; p < 0.001) than those who had with ≤8 scans. For each additional abdominopelvic CT scan, the adjusted HR for SPM was 1.09 (95% confidence interval (CI), 1.03–1.14). Similar results were observed in the Korean National Health Insurance Service cohort (adjusted HR, 1.14; 95% CI, 1.07–1.22). Significantly elevated risk of SPM was still observed when considering a 2-year latency period (adjusted HR, 2.43; 95% CI, 1.37–4.48) and a 3-year latency period (adjusted HR, 2.17; 95% CI, 1.06–4.47). Frequent abdominopelvic CT scans are associated with an elevated risk of SPMs after the treatment of EGC. Thus, physicians need to weigh carefully the clinical benefits of CT examinations against the potential risks of radiation exposure.

Hepatocellular carcinoma and the risk of de novo malignancies after liver transplantation - a multicenter cohort study.

Patients with hepatocellular carcinoma (HCC) are at high risk of second primary malignancies. As HCC has become the leading indication of liver transplant (LT), the aim of this study was to investigate whether the presence of HCC before LT could influence the onset of de novo malignancies (DNM). A cohort study was conducted on 2653 LT recipients. Hazard ratios (HR) of DNM development for patients transplanted for HCC (HCC patients) were compared with those of patients without any previous malignancy (non-HCC patients). All models were adjusted for sex, age, calendar year at transplant, and liver disease etiology. Throughout 17903 person-years, 6.6% of HCC patients and 7.4% of non-HCC patients developed DNM (202 cases). The median time from LT to first DNM diagnosis was shorter for solid tumors in HCC patients (2.7 vs 4.5years for HCC and non-HCC patients, respectively, P<0.01). HCC patients were at a higher risk of bladder cancer and skin melanoma. There were no differences in cumulative DNM-specific mortality by HCC status. This study suggests that primary HCC could be a risk factor for DNM in LT recipients, allowing for risk stratification and screening individualization.

Risk of second primary malignancy after minor salivary gland cancer: A Surveillance, Epidemiology, and End Results database analysis.

Minor salivary gland cancer (MiSGC) is a group of tumors with varied disease course in the head and neck. We evaluated the risk of a second primary malignancy (SPM) in MiSGC patients and identified possible prognostic factors for survival using a large population database. We used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data to evaluate the risk and prognosis of SPM in patients diagnosed with MiSGC. The risk of SPM increased in MiSGC patients compared with the endemic rate. The risk of SPM was slightly greater in female patients and who underwent radiotherapy. Age at primary diagnosis, sex, race, year of diagnosis, SEER stage, radiotherapy, SPM, histology, and tumor site were significant survival prognostic indicators of MiSGC patients. Radiotherapy and female sex were risk factors for SPM after MiSGC. Long-term surveillance for SPM was important in MiSGC patients.

Abstract PS7-16: Increased cancer mortality after second primary malignancy among breast cancer survivors

Abstract Background: Due to advances in early detection and treatment, the number of breast cancer survivors in the US is expected to increase to 5 million by 2030. Although it is well established that breast cancer survivors are at increased risk of second primary malignancy (SPM), there is limited data on the impact of a SPM on overall and cancer-specific mortality compared to women with a first primary cancer. This information could inform prognosis for women with breast cancer as well as screening and treatment recommendations. Methods: A retrospective cohort study was conducted using the Surveillance, Epidemiology, and End Results (SEER) 18 database, which collected cancer incidence and mortality from 18 US cancer registries (represents 28% of US population) between 2000 and 2016. For this analysis, we focused on the top 10 SPM in breast cancer survivors: breast cancer, lung cancer, colorectal cancer, uterine cancer, lymphoma, melanoma, thyroid cancer, pancreatic cancer, ovarian cancer, and leukemia. Propensity scores were used to match SPM with first primary cancer 1:1 on race, primary site, year of diagnosis, age of diagnosis, tumor stage, and treatments (surgery, chemotherapy, and radiotherapy). Hazard ratio (HR) and 95% confidence interval (CI) for cancer-specific death comparing SPM to first primary cancer were estimated from Cox proportional hazard regression, accounting for competing risk of death from conditions other than cancer. Subgroup analyses were conducted by SPM tumor stage, SPM primary site, and time interval between first breast cancer and SPM diagnosis. Results: The study population included 31,712 breast cancer survivors with SPM and 1,471,886 women with first primaries. Women with SPM were older (mean age of 66.6 years) than first primary cancers (mean age of 62.1 years). 52.8% of SPM and 47.5% of first primary cancers were diagnosed at local stage. Women with SPM had higher cancer mortality than women with first primary cancer (HR: 1.27, 95%CI: 1.23-1.30). Mortality difference was larger among local stage SPM (HR: 1.95, 95%CI: 1.82-2.08) and regional stage (HR: 1.40, 95%CI: 1.33-1.47) than for distant stage (HR:1.10, 95%CI:1.06-1.14). Among the top 10 SPM, increased mortality was observed for thyroid cancer (HR: 3.02, 95%CI: 1.96-4.67), breast cancer (HR: 2.26, 95%CI: 2.11-2.42), and melanoma (HR: 1.76, 95%CI: 1.36-2.28). There was no statistically significant difference in mortality for second lung (HR: 1.06, 95%CI: 1.00-1.17) and pancreatic cancer (HR: 0.93, 95%CI: 0.82-1.06). Larger mortality difference comparing SPM to first primary cancer was observed for SPM diagnosed within 5 years (HR: 1.39, 95%CI: 1.35-1.44) than after 5 years (HR: 1.09, 95%CI: 1.04-1.13). Conclusion: Breast cancer survivors with a SPM had higher cancer-specific mortality overall and for several cancers compared to women diagnosed with the same type of cancer for the first time suggesting that prior breast cancer is an important prognostic factor. Our results support the evaluation of improved risk stratification and/or novel screening and treatment approaches to improve outcomes from second cancer in breast cancer survivors. Citation Format: Zhengyi Deng, Miranda R Jones, Kala Visvanathan. Increased cancer mortality after second primary malignancy among breast cancer survivors [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS7-16.

Lung Cancer Screening With Low Dose Computed Tomography in Patients With and Without Prior History of Cancer in the National Lung Screening Trial

IntroductionPatients with a prior history of cancer (PHC) are at increased risk of second primary malignancy, of which lung cancer is the most common. We compared the performance metrics of positive screening rates and cancer detection rates (CDRs) among those with versus without PHC. MethodsWe conducted a secondary analysis of 26,366 National Lung Screening Trial participants screened with low dose computed tomography between August 2002 and September 2007. We evaluated absolute rates and age-adjusted relative risks (RRs) of positive screening rates on the basis of retrospective Lung CT Screening Reporting & Data System (Lung-RADS) application, invasive diagnostic procedure rate, complication rate, and CDR in those with versus without PHC using a binary logistic regression model using Firth’s penalized likelihood. We also compared cancer type, stage, and treatment in those with versus without PHC. ResultsA total of 4.1% (n = 1071) of patients had PHC. Age-adjusted rates of positive findings were similar in those with versus without PHC (Baseline: PHC = 13.7% versus no PHC = 13.3%, RR [95% confidence interval (CI)]: 1.04 [0.88–1.24]; Subsequent: PHC = 5.6% versus no PHC = 5.5%, RR [95% CI]: 1.02 [0.84–1.23]). Age-adjusted CDRs were higher in those with versus without PHC on baseline (PHC=1.9% versus no PHC = 0.8%, RR [95% CI]: 2.51 [1.67–3.81]) but not on subsequent screenings (PHC = 0.6% versus no PHC = 0.4%, RR [95% CI]: 1.37 [0.99–1.93]). There were no differences in cancer stage, type, or treatment by PHC status. ConclusionsPatients with PHC may benefit from lung cancer screening, and with their providers, should be made aware of the possibility of higher cancer detection, invasive procedures, and complication rates on baseline lung cancer screening, but not on subsequent low dose computed tomography screening examinations.

Survival analysis of second primary malignancies after cervical cancer using a competing risk model: implications for prevention and surveillance.

BackgroundPrevious studies have reported an increased risk for second primary malignancies (SPMs) after cervical cancer (CC). This study aims to quantify and assess the risk of developing SPMs in long-term survivors of CC.MethodsA population-based cohort of CC patients aged 20–79 years was obtained from the Surveillance, Epidemiology, and End Results (SEER) database. A competing risk model and corresponding nomogram were constructed to predict the 3-, 5-, and 10-year cumulative risks of SPMs. A Fine-Gray plot was created to validate the model. Finally, we performed decision curve analysis (DCA) to evaluate the clinical usefulness of the model by calculating the net benefit.ResultsA total of 34,295 patients were identified, and approximately 6.3% of the study participants developed SPMs. According to the multivariable competing-risk model, older black CC survivors with localized disease who were treated with radiation therapy were more susceptible to SPMs. The 3-, 5-, and 10-year cumulative incidences of SPMs were 2.5%, 3.6%, and 6.2%, respectively. Calibration curves showed good agreement between the predicted and observed models. The DCA yielded a wide range of risk thresholds at which the net benefits could be obtained from our proposed model.ConclusionsThis study provides physicians with a practical, individualized prognostic estimate to assess the risk of SPMs among CC survivors. CC survivors remain at a high risk of developing SPMs, and further surveillance should focus especially on the patients with black race, older age, localized disease, or those having received radiation therapy.

The Impact of Radiotherapy on the Incidence of Secondary Malignancies: A Pan-Cancer Study in the US SEER Cancer Registries.

The population of cancer patients with second primary malignancies (SPMs) is rapidly growing. The relationship between radiotherapy and SPMs for some types of tumors is unknown or debated. In this study, we identify 24 types of first primary malignancies (FPMs) between 2004 and 2015 in the Surveillance, Epidemiology, and End Results (SEER) database. Patients in the radiotherapy group were matched to those in the no radiotherapy group with a matching ratio of 1:1. After propensity-score matching (PSM), additional competing risk regression analyses were performed to calculate the efficacy of radiotherapy to SPMs in the PSM-adjusted population. In addition, the Fine and Gray model was utilized in the primary cohorts, and stratified analyses were performed based on surgery. This study includes a total of 2,831,789 eligible patients with tumors diagnosed from 2004 to 2015 in the SEER 18 database, amongst whom 100,194 (3.5%) patients developed SPMs. We observe higher risks of SPMs associated with radiotherapy in several types of tumors in the PSM-adjusted populations (small bowel adenocarcinoma, small cell lung carcinoma, prostate adenocarcinoma, urinary bladder transitional cell carcinoma, invasive ductal breast carcinoma, invasive lobular breast carcinoma, and Hodgkin lymphoma). The results in the PSM-adjusted populations were consistent with outcomes in the multivariable competing risk models. Meanwhile, in subgroup analyses stratified by surgery, some other types of tumor (except for those with positive results in the PSM-adjusted cohorts) with radiotherapy were also associated with a higher prevalence of SPMs in the subgroups of surgical treatment (pancreatic adenocarcinoma, rectal adenocarcinoma, lung adenocarcinoma and follicular thyroid carcinoma in the surgery subgroups). The impact of radiotherapy on the incidence of secondary malignancies is distinct in different types of cancer. These findings merit further investigation and may ultimately impact treatment decision-making for tumor management.

Risk Factors and Specific Cancer Types of Second Primary Malignancies in Patients With Breast Cancer Receiving Adjuvant Radiotherapy: A Case–Control Cohort Study Based on the SEER Database

Patients with breast cancer can survive and live a long, cancer-free life; however, late complications of treatment, such as second primary malignancies (SPMs), have emerged as a competing cause of death and morbidity. We conducted a long-term population-based cohort study to identify the risk factors for SPMs and specific secondary cancer types after various latency periods of irradiated breast cancer. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (95% CI) for independent risk factors for SPM. We also calculated the HR of each specific cancer type and the latency time to specific SPMs. The risk of SPM was statistically significantly higher in patients with adjuvant RT than in patients without adjuvant RT (adjusted HR [aHR]: 1.105, 95% CI: 1.013-1.206). Compared with the control group, the case group had significantly increased risks of contralateral breast cancer (aHR: 1.268, 95% CI: 1.112-1.445), lung cancer (aHR: 1.218, 95% CI: 1.049-1.565), and urinary system cancer (aHR: 1.702, 95% CI: 1.140-2.543). Adjuvant RT for breast cancer increases the risk of SPM. Contralateral breast cancer, lung cancer, and bladder cancer were significant SPMs after breast RT, although the cumulative risk of SPM was low, at approximately 6, 10, and 13 cancers per 1000 women with irradiated breasts at latency periods of 5, 10, and 15 years, respectively, after breast RT.

Risk of second malignancy in patients with ovarian clear cell carcinoma

ObjectiveOvarian clear cell carcinoma has unique clinical and molecular features compared with other epithelial ovarian cancer histologies. Our objective was to describe the incidence of second primary malignancy in patients...