Risk Of Second Primary Malignancies Research Articles

Increased risk of second primary malignancies among endometrial cancer survivors receiving surgery alone: A population-based analysis.

BackgroundWomen with endometrial cancer (EC) have favorable prognoses, leaving them vulnerable to the development of second primary cancers (SPCs). We investigated the SPC risk and survival outcomes among EC patients treated with surgery alone in order to exclude the impact of adjuvant treatment on the results.MethodsData from the Taiwan Cancer Registry from 1995 to 2013 were analyzed. Standardized incidence ratios (SIRs) of SPCs among EC survivors were calculated.ResultsAmong 7725 women enrolled, 478 developed an SPC. The overall SIR for SPCs in EC survivors was 2.84 (95% confidence interval [CI] 2.59–3.10) compared with the general female population. Women diagnosed with EC at age <50 years had a higher SIR for an SPC than those diagnosed at age ≥50 years (SIR = 4.38 vs. 1.28). The most frequent site of an SPC was the small intestine (SIR = 8.39, 95% CI 2.72–19.58), followed by the kidney (SIR = 4.84, 95% CI 1.78–10.54), and oral cavity (SIR = 4.52, 95% CI 2.17–8.31). Women, regardless of age at EC diagnosis, had significantly higher SIRs for subsequent breast, colorectal, lung, and thyroid cancer, and lymphoma. Women with an SPC had shorter overall survival than those without (5‐year: 88.9 vs. 94.2%, 10‐year: 71.3 vs. 89.8%, 15‐year: 62.3 vs. 86.1%, and 20‐year: 47.6 vs. 81.1%, all ps<0.001).ConclusionsEven women treated for EC with surgery alone, especially young EC survivors, had an increased risk of SPCs. Genetic counseling/testing is recommended for young EC patients, and all are recommended to receive regular surveillance and screening for breast, colorectal, and lung cancers.

The risk and prognosis of secondary primary malignancy in lung cancer: a population-based study.

Aim: To assess and predict risk and prognosis of lung cancer (LC) patients with second primary malignancy (SPM). Methods: LC patients diagnosed from 1992 to 2016 were obtained through the Surveillance, Epidemiology, and End Results database. Standardized incidence ratios were calculated to evaluate SPM risk. Cox regression and competing risk models were applied to assess the factors associated with overall survival, SPM development and LC-specific survival. Nomograms were built to predict SPM probability and overall survival. Results & conclusion: LC patients remain at higher risk of SPM even though the incidence declines. Patients with SPM have a better prognosis than patients without SPM. The consistency indexes for nomograms of SPM probability and overall survival are 0.605 (95% CI: 0.598-0.611) and 0.644 (95% CI: 0.638-0.650), respectively.

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.

Cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia: a systematic review of the literature.

The continuous improvement of life expectancy of patients with chronic lymphocytic leukemia (CLL) has resulted in increased risk of second primary malignancy that potentially may affect survival and quality of life of CLL patients. We performed a systematic review to assess the risk and the clinical‐pathological features and prognosis of cutaneous squamous cell carcinoma (cSCC) in patients with CLL. We searched PubMed, Embase, and Cochrane Central Register of Control Trials databases for articles published from database inception to December 31, 2019. English‐language studies reporting original data on patients with a specific diagnosis of CLL and cSCC were included. Data were extracted using a standardized extraction form, and any discordance was resolved by consensus. Descriptive data were generated by pooling patients from eligible studies. Of the 4588 non‐duplicate records identified, 55 articles met our inclusion criteria. These studies reported that CLL patients have a 3.2% prevalence of cSCC, with an 11.5% cSCC‐related lethality and an overall risk of metastasis of 5.7% (7.3% for regional lymph node involvement and 3.8% for distant metastasis). The quality of evidence was limited by the high heterogeneity in the design, populations, and objectives of the included studies. This systematic review suggests that cSCC in CLL patients tends to behave less aggressively compared with the solid organ transplant recipients but has a higher morbidity and mortality than in the general population. Future prospective studies are needed to increase the quality of evidence and to determine the best treatment modalities and screening intervals for these patients.

Increased Risk of Second Primary Malignancy and Mortality at ten Years After Stem Cell Transplant for Multiple Myeloma: An Analysis of 14,532 Patients.

BackgroundThe landscape for patients with multiple myeloma has improved dramatically over the last 15 years. Immunomodulatory imide drugs (IMiDs) have shown great efficacy in both the setting of initial therapy and as maintenance after autologous stem cell transplant (ASCT). Concern has arisen, however, regarding the risk of second primary malignancies (SPMs) that appear to be associated with the use of IMiD agents. SPMs are a known sequela of multiple myeloma treatment, particularly as a consequence of maintenance lenalidomide status-post stem cell transplant (SCT). The benefit of SCT has become less clear with the utilization of newer, more effective initial therapies.ObjectivesTo determine the effect of SCT on SPM risk and overall survival in multiple myeloma patients at 5 and 10 years after treatment initiation.MethodsWe used TriNetX, a global federated health research network providing access to electronic medical records (diagnoses, procedures, medications, laboratory values, genomic information) from approximately 58 million patients in 49 large healthcare organizations. We created two patient cohorts who had all received treatment with thalidomide, lenalidomide, or pomalidomide. One cohort had received SCT while the other had not. Both cohorts were then analyzed for the development of all non-myeloma malignancies which occurred at least one year after initiation of treatment.ResultsAt 5 years, SPMs were 5.8% more likely in patients who received stem cell transplant (22.4% vs 16.6%, RR 0.741, p value <0.0001) but 5-year survival favored transplanted patients by 2.38% (64.85% vs 62.474%, p value 0.0044). 10-year survival favored patients who did not receive transplant by 1.44% (42.279% vs 40.838%, p value 0.0279). The Kaplan-Meier curves cross at year 6.ConclusionsIt has previously been shown that the use of alkylating agents in myeloma patients significantly increases the risk of SPM, but that difference had curiously not been shown to have a negative impact on survival. Our analysis shows that this negative survival impact does exist but requires six or more years of follow up to become evident. Recent analyses from studies using older regimens show no overall survival benefit from the use of stem cell transplant. As non-transplant regimens become more effective at producing minimal residual disease (MRD) negativity, it seems that transplantation for myeloma patients will soon be regarded as unnecessary or even detrimental.

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

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

Effect of Autologous Hematopoietic Stem Cell Transplant (aHSCT) on the Development of Second Primary Malignancies (SPM) in Multiple Myeloma Patients

Abstract Background: Since the 1960s, an increased risk of SPMs in multiple myeloma (MM) patients has been noted but less consequential due to relatively short survival. Given considerably improved survival as well as the potential association with modern anti-myeloma therapy, reassessment of this risk is prudent. Prior studies of aHSCT recipients have calculated standardized incidence ratios compared to the general population, but have not compared the cumulative incidence of SPMs among myeloma patients undergoing aHSCT to those who do not. Thus, a direct comparison of the effect of aHSCT on development of SPMs in MM patients is necessary to better advise patients and physicians on the potential risks of this treatment in the modern era. Methods: Patients diagnosed with MM between 1991 and 2013 were identified in the California Cancer Registry linked to the California hospital Patient Discharge Database. Inclusion criteria included a first primary diagnosis of MM and a minimum 1 year of follow up. SPMs were defined as distinct malignancies arising ≥1 year after MM diagnosis. The cumulative incidence (CI) of developing any SPM, solid tumors, and hematologic malignancies, and associated 95% confidence intervals were computed, accounting for the competing risk of death. To compare the cumulative incidence of SPMs between aHSCT recipients and those without aHSCT, patients were matched 1:2 on age, year of diagnosis, race/ethnicity, socioeconomic status and comorbidities. Multivariable cox proportional hazards regression models, using the methods of Fine and Gray to account for competing risk of death, and stratified for variables that did not meet the proportional hazards assumption, estimated the effect of aHSCT on the risk of SPM development accounting for baseline demographics. Results: Among 16,331 patients, 933 (5.7%) developed a SPM ≥1 year after diagnosis. Of these, 119 (12.8%) were hematologic malignancies, primarily leukemia (81, 9%). The most common solid tumors were malignancies of the digestive (184, 19.7%), respiratory (119, 12.8%), and male genital (115, 12.3%) systems. An additional 310 SPMs were diagnosed The 5- and 10-year CI of developing any SPM, accounting for the competing risk of death, was 4% (3.7% - 4.3%) and 6.6% (6.2% - 7.1%) respectively. There is no plateau in the incidence of SPM development (Figure). The 5- and 10-year cumulative incidence of developing solid SPM was 3.5% (3.3% - 3.9%) and 5.7% (5.3% - 6.2%). The 5- and 10-year cumulative incidence of developing hematologic SPM was 0.5% (0.4% - 0.6%) and 0.9% (0.7% - 1.1%). In the matched analysis, the 5- and 10-year CI of developing a SPM was similar among aHSCT recipients [5-year: 4.8% (3.6% - 5.9%); 10-year: 9.1% (7.7% - 10.7%)] and among non-aHSCT recipients [5-year: 4.7% (4.0% - 5.5%); 10-year: 7.5% (6.5% - 8.6%)] (Figure Part A) (P=0.26). However, the CI of hematologic SPMs differed among the aHSCT and non-aHSCT groups reaching 2.1% (1.4% - 2.9%) among aHSCT recipients vs 0.8% (0.5% - 1.2%) at 10 years (P = 0.005). There was no difference in the CI of solid SPMs between the two groups (Figure C) (P=0.98). Multivariable models adjusted for baseline characteristics and the competing of risk of death identified no increased risk of developing SPMs overall among aHSCT recipients (adjusted hazard ratio (aHR) 1.13, 95% CI 0.94 - 1.37). The risk of developing hematologic SPMs was increased in the aHSCT recipients (aHR 1.65, 1.03 - 2.63), while the risk of developing solid SPMs was not (aHR 1.06, 0.86 - 1.31). Era of diagnosis (1991-97, 1998-2002, 2003-07, 2008-13) was not associated with an increased risk of SPMs. Conclusions: MM patients are at risk for SPMs and we observed that the cumulative incidence increases over time. The use of aHSCT as part of treatment and the era of diagnosis were not associated with a change in risk of overall SPM development. Though no difference in SPM development over time was noted, follow up time during eras when continuous therapy was more common are still short. A small but significant increase in hematologic SPMs was noted among aHSCT recipients. As MM patients continue to live longer, efforts to effectively screen and prevent SPMs are warranted. Download : Download high-res image (103KB) Download : Download full-size image Figure . Disclosures Rosenberg: Amgen: Speakers Bureau. Tuscano: Novartis: Research Funding; Spectrum: Research Funding; Celgene: Research Funding, Speakers Bureau; Takeda: Research Funding; Amgen: Speakers Bureau. Jonas: AbbVie, Celgene, Daiichi Sankyo, Pharmacyclics, Genentech/Roche, Glycomimetics, Esanex, Kalobios: Research Funding; Rigel: Consultancy; Celgene: Membership on an entity's Board of Directors or advisory committees. Abedi: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; California Institute of Regenerative Medicine: Research Funding; Seattle Genetics: Speakers Bureau; Amgen: Research Funding; BMS: Speakers Bureau; Takeda: Speakers Bureau; Gilead: Speakers Bureau. Wun: Pfizer: Other: Steering Committee: RESET study, Research Funding; Janssen: Other: Steering Committee for Cassini Study and Callisto Program, Research Funding.

Second Primary Malignancies in Patients with Non-Hodgkin Lymphoma

Introduction: Increased risk of second primary malignancies (SPMs) has been reported in Hodgkin lymphoma as well as non-Hodgkin lymphoma (NHL) patients. NHLs are heterogeneous with different genetic, immunophenotypic, and clinical features. Some NHLs are aggressive but potentially curable, such as Burkitt lymphoma (BL) and diffuse large B-cell lymphoma (DLBCL), while other NHLs are indolent but generally incurable, such as follicular lymphoma (FL) and marginal zone lymphoma (MZL). We hypothesized that the risk for developing SPMs in patients with different types of NHL would differ significantly. In this study, we compared the incidences of SPMs in patients with various major types of NHL, including BL, DLBCL, mantle cell lymphoma (MCL), FL and MZL, using population-based cancer registry data.Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to identify patients with NHL. While the most updated database includes 1973-2014 data, only the more recent 1991-2014 data were used in this study. NHL cases were identified using International Classification of Disease for Oncology, third edition (ICD-O-3) morphology codes (BL: 9687; DLBCL: 9680; MCL: 9673; FL: 9690, 9691, 9695, 9698; MZL: 9699). The SEER sequence number was used to limit the study population to those who had NHL as their only primary malignancy throughout their lives (code 00), and those who had multiple primary malignancies with NHL as their first malignancy (code 01). For the latter group, information on SPMs was obtained by using the same patient code and a defined sequence number (code 02). Further study criteria included age 18 or greater, pathology confirmation of malignancy diagnosis, and having active follow-up. Categorical data were analyzed using Chi-square test, and time-to-event data were analyzed using Kaplan-Meier estimator. Case identification and all statistical analyses were performed using SAS (v9.4).Results: A total of 154,961 patients were included in the final analyses, 3,716 with BL, 80,734 with DLBCL, 8,323 with MCL, 44,055 with FL, and 18,133 with MZL. SPMs developed in 14,357 patients, with an overall incidence of 9.26%. The incidences of SPMs varied significantly in patients with different types of NHL, with a rate of 5.22% in BL, 7.34% in DLBCL, 9.14% in MCL, 11.66% in FL, and 12.90% in MZL (Table 1). The differences of SPM incidences between any two types of NHL were statistically significant (all P < 0.05). Male and female patients with BL had similar incidences of SPMs (5.04 % vs 5.72%, P= 0.45). Male patients with DLBCL (7.98% vs 6.58%), MCL (9.58% vs 8.16%), FL (12.69% vs 10.63%) and MZL (14.46% vs 11.62%) had higher incidences of SPMs compared to female patients (all P < 0.05). Hematological malignancies (leukemia and other lymphomas) were the most common SPMs in patients with all types of NHL. With one exception (second lung cancer in BL patients), the most common solid SPMs in NHL patients were lung cancer, prostate cancer, and breast cancer, followed closely by colorectal cancer, consistent with the pattern in general population. The next most common solid SPM was melanoma, as opposed to bladder cancer in the general population. Thyroid cancer, while less common, occurred early in patients with NHL, with the shortest median time to develop SPM.Conclusions: Close to 10% of patients with NHL developed SPMs. The incidence of SPMs correlated with the aggressiveness and potential curability of NHL, with the lowest SPM incidence in BL, followed by DLBCL, MCL, FL and MZL. Male DLBCL, MCL, FL and MZL patients had higher incidences of SPMs compared to female patients. Hematological malignancy was the most common SPM in NHL patients. The most common solid SPMs in NHL patients were lung, prostate, breast, colorectal cancers and melanoma. Thyroid cancer as a SPM tended to develop early in NHL patients. Patients with NHL must be followed long-term for SPM, a potential complication of survival. [Display omitted] DisclosuresNowakowski:Morphosys: Consultancy, Research Funding; pharmacyclics: Consultancy; Abbvie: Consultancy; Genetech: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Nanostring: Research Funding; celgene: Consultancy, Research Funding. Wang:Juno Therapeutic: Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Karyopharm: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Kite Pharma: Research Funding; BeiGene: Research Funding; Oncoceutics: Research Funding; Novartis: Research Funding; Karus: Research Funding; Oncternal: Research Funding; Celgene: Honoraria, Research Funding; Asana: Research Funding; Acerta Pharma: Consultancy, Honoraria, Research Funding.

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 &lt; 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.