Risk Of Second Primary Malignancies Research Articles

Second Primary Cancer after Treating Gastrointestinal Cancer

Advances in diagnosis and therapeutic technologies have brought increased life expectancy for most cancers, but paradoxically it also has increased the risk of second primary malignancies. Cancer survivors have a higher risk of developing cancer than the general population. This suggests that more studies are needed to develop screen and management programs for cancer survivors, especially patients with gastrointestinal cancers, which are the most common cancers in Korea.

The volume of liver irradiated during modern free-breathing breast radiotherapy: Implications for theory and practice

IntroductionIncidental liver irradiation during breast radiotherapy can increase the risk of second primary malignancy and induce adverse inflammatory states. This study establishes the volume of liver irradiated during free-breathing breast radiotherapy. Novel associations between liver dose-volume data and systemic interleukin-6 soluble receptor and blood counts are evaluated. MethodsThe volume of liver within the 10%, 50% and 90% isodose was determined for 100 women with stage 0 to II breast carcinoma undergoing 40Gy in 15 fractions over three weeks tangential irradiation. Blood counts and interleukin 6 soluble receptor concentration were recorded before, during and four weeks after radiotherapy. Dose-volume data for right-sided treatments was associated with longitudinal measures at bivariate and multivariable levels. ResultsA maximum of 226cm3 (19%), 92 cm3 (8%) and 62 cm3 (5%) of the liver was irradiated within the 10%, 50% and 90% isodose. Liver irradiation was almost exclusively a feature of the 52 right-sided treatments and was strongly correlated with breast volume (ρ = 0.7, p < 0.0001). Liver V10% was significantly associated with interleukin-6 soluble receptor concentration four weeks post-radiotherapy (beta = 0.38, p = 0.01) after controlling for theoretical confounding variables. ConclusionUp to 8% of the liver is irradiated within the primary beam during local right-sided breast radiotherapy. Select use of a deep inspiration breath hold technique would reduce this volume, and minimise the risk of radiation-induced malignancy and acute systemic elevation of inflammatory interleukin 6 soluble receptor.

Increasing therapy-related myeloid neoplasms in multiple myeloma.

Despite the longer survival achieved in multiple myeloma (MM) patients due to new therapy strategies, a concern is emerging regarding an increased risk of secondary primary malignancies (SPMs) and how to characterize those patients at risk. We performed a retrospective study covering a 28-year follow-up period (1991-2018) in a tertiary single institution. Data of 403 MM patients were recorded and compared with the epidemiologic register of the population area covered by our centre, calculating the standardize incidence ratio (SIR) for the different types of SPMs diagnosed in the MM cohort. Fine and Gray regression models were used to identify risk factors for SPMs. Out of the 403 MM patients, 23 (5.7%) developed SPMs: 13 therapy-related myeloid (TRM) malignancies (10 of them (77%) myelodysplastic syndrome (MDS), 1 acute lymphoid leukaemia and 9 solid neoplasms. In the MM cohort, the relative risk of MDS was significantly higher than in the general population. Survival of patients with TRM malignancies was poor with a median of 4 months from the diagnosis, and most of them showed complex karyotype. Within the MM subset, multivariable analysis showed a higher risk of TRM malignancies in patients that previously received prolonged treatment with lenalidomide (>18 months). Though the improvement in MM outcome during the last decades is an unprecedented achievement, it has been accompanied by the rise in TRM malignancies with complex cytogenetic profile and poor prognosis that are in the need of an improved biologic and therapeutic approach.

Trends in the Risk of Second Primary Malignancies (SPMs) Among Survivors of Chronic Lymphocytic Leukemia(CLL)

Background: CLL is the most common leukemia diagnosis in adults and its treatment has undergone significant change from chemotherapy, to immunotherapy and now targeted kinase inhibitors, leading to improved overall survival (OS). With improving survivorship, SPMs can occur but an in-depth analysis of risks and trends of SPMs in CLL survivors is lacking. We performed a population-based analysis to evaluate this.Methods: Patients in the Surveillance, Epidemiology and End Results (SEER) database diagnosed with CLL between 1973-2015 were included. Due to variation in management techniques over time, the cohort was divided in four time periods: 1973-1982, 1983-1992, 1993-2002 and 2003-2015. We evaluated differences in risk for SPMs among CLL survivors compared to risk of individual malignancies expected in the general population during these time periods and studied the effect of demographics and time since CLL diagnosis.Results: Over a nearly 270,000 person-year follow up, 6,467 new SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.2 (95% CI 1.17-1.23), which resulted in a 39 excess cancers per 10,000 population. The CLL survivors had a 20% overall increased risk of developing SPMs (excluding non-squamous skin cancer) compared to the general population. The risks for both solid (SIR 1.15 CI 95% 1.12-1.18) and hematological malignancies (SIR 1.61 95% CI 1.5-1.73) was higher than the expected in the general population. However, the risk for individual cancers was heterogeneous. The tumors associated with the highest risk were Hodgkin lymphoma (almost 8 times higher), Kaposi Sarcoma (4 times), non-epithelial skin cancers (4 times), salivary gland cancer (3 times) and acute lymphocytic leukemia (3 times). In contrast, tumors in the hepatobiliary system, female breast and female genital system were associated with a lower risk than the general population. The highest SIR across the study periods was observed in the younger population (ages 15-49). Although the risk increased in all ethnicities, it was statistically significant only in Caucasians. There was no gender-wise difference in SIR during any of the four time periods. A statistically significant increase in SIR was observed for both men and women from 1973-1982 to 2003-2015. This was mostly due to an increase in risk of hematological malignancies from 1.08 early in the study to 2.56 in the most recent study period. The SIR in solid tumors did not change significantly over time; in absolute terms, however, lung carcinoma contributed the most to the excess risk, followed by non-epithelial skin cancers and non-Hodgkin's lymphoma. The risk of developing a SPM was higher for the CLL survivors during most of the latency periods, but it was statistically significant during the 2-5 months and 12-59 months after diagnosis. A multivariate analysis was conducted to evaluate the impact of period of diagnosis on the development of SPMs among these patients. After adjusting for gender, ethnicity, radiation therapy, chemotherapy, and age at diagnosis of CLL, patients diagnosed with CLL in the most recent time period were at 45% higher risk of developing SPMs as compared to the patient diagnosed during 1973-1982 (Hazard ratio(HR) =1.45 95%CI:1.34-1.6, p<0.001). Moreover increased HRs were also observed for 1983-1992 and 1993-2002 time periods (Fig. 1)Conclusions: With improving therapeutics for cancer treatment, survivorship is improving as well and the risk of SPMs needs to be better understood and addressed. This is truer for CLL, where majority of patients have a favorable survival. The risk of SPMs was 20% higher in CLL survivors than in the general population and was most prominent in the survivors aged 15-49 years at the time of CLL diagnosis. The risk of individual malignancies may be heterogenous but there has been an increase in risk of SPMs over time, mainly due to an increase of secondary hematological malignancies in recent years. Active survivorship plans and long-term surveillance for SPMs is crucial for improved outcomes of patients with a history of CLL. DisclosuresAilawadhi:Janssen: Consultancy; Celgene: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Pharmacyclics: Research Funding.

Risk of Second Primary Malignancies in Chronic Lymphocytic Leukemia

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

Maintenance Therapy with the Oral Proteasome Inhibitor (PI) Ixazomib Significantly Prolongs Progression-Free Survival (PFS) Following Autologous Stem Cell Transplantation (ASCT) in Patients with Newly Diagnosed Multiple Myeloma (NDMM): Phase 3 Tourmaline-MM3 Trial

Maintenance Therapy with the Oral Proteasome Inhibitor (PI) Ixazomib Significantly Prolongs Progression-Free Survival (PFS) Following Autologous Stem Cell Transplantation (ASCT) in Patients with Newly Diagnosed Multiple Myeloma (NDMM): Phase 3 Tourmaline-MM3 Trial

Second primary malignancy risk after radiotherapy in rectal cancer survivors.

AIMTo investigate second primary malignancy (SPM) risk after radiotherapy in rectal cancer survivorsMETHODSWe used Taiwan’s National Health Insurance Research Database to identify rectal cancer patients between 1996 and 2011. Surgery-alone, preoperative short course, preoperative long course, and post-operative radiotherapy groups were defined. The overall and site-specific SPM incidence rates were compared among the radiotherapy groups by multivariate Cox regression, taking chemotherapy and comorbidities into account. Sensitivity tests were performed for attained-year adjustment and long-term survivors analysis.RESULTSA total of 28220 patients were analyzed. The 10-year cumulative SPM incidence was 7.8% [95% confidence interval (CI): 7.2%-8.2%] using a competing risk model. The most common sites of SPM were the lung, liver, and prostate. Radiotherapy was not associated with increased SPM risk in multi-variate Cox model (hazard ratio = 1.05, 95%CI: 0.91-1.21, P = 0.494). The SPM hazard remained unchanged in 10-year-survivors. In addition, no SPM risk difference was found between the preoperative radiotherapy and postoperative radiotherapy groups.CONCLUSIONIn this large population-based cohort study, we demonstrated that radiotherapy had no increase in SPM.

Second Primary Malignancies and Cardiovascular Mortality in Hodgkin Disease (HD) Survivors – A SEER Database Study

Over the last few decades there has been significant improvements in survival in patients (pts) with HD. But long-term HD survivors, especially those treated with radiation therapy (RT) have an increased risk of second primary malignancy (SPM) and cardiovascular disease (CVD) related mortality. We conducted this population based study to analyze trends in CVD related mortality and incidence of lung and thyroid cancer (CA) in HD survivors treated with RT. We used the SEER 9 database to calculate the Standardized Incidence Ratio (SIR) and Excess Absolute Risk (EAR) of lung and thyroid CA as SPM in survivors of HD diagnosed between 1973 and 2011, who were treated with RT. Poisson regression models were used to calculate adjusted incidence of lung and thyroid CA. We also divided the pts 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 (YOD). Poisson regression models were used to calculate adjusted CVD mortality by YOD 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 YOD. We identified 11,916 HD cases that received RT, who were followed up for a median duration of 160 months (range – 12 to 480 months). 319 pts developed lung CA (SIR of 3.72, 95% CI 3.32 – 4.15; EAR of 13.19 per 10,000 person years at risk (PYAR)) and 86 pts developed thyroid CA (SIR of 3.67, 95% CI 2.94 – 4.53; EAR of 3.54 per 10,000 PYAR). Median ages at diagnosis of secondary lung and thyroid CA were 59 yrs and 42 yrs, with median latency periods of 16 yrs and 17 yrs respectively. 965 pts among 11,916 pts who received RT died from CVD while the number of CVD deaths was 1,182 among the 12,507 pts who were not given RT. Using Poisson regression models, we calculated the adjusted incidence of secondary lung CA and thyroid CA and the adjusted mortality from CVD, by YOD. YOD, 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 CA declined at an EAPC of -2.68 (95% CI -13.06 to -3.92) and that of thyroid CA declined at an EAPC of -3.35 (95% CI -5.73 to -1.00). Over the same period, CVD mortality per 10,000 PYAR for pts who received RT declined at an EAPC of -4.34 (95% CI -4.97 to -3.73) and that of pts who did not receive RT declined at an EAPC of -1.92 (95% CI -2.47 to -1.39). We observed a decline in incidence of lung and thyroid CA and CVD mortality in HD survivors over the study period. The decline in CVD mortality over time in pts who received RT was steeper compared to that of pts 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.

Multiple Primary Malignancies in Patients with Anal Squamous Cell Carcinoma

Prior studies examining the risk of second primary malignancy (SPM) after a first primary cancer generally have used large datasets such as the Surveillance, Epidemiology, and End Results (SEER) registry and excluded survivors of previous primaries and developers of synchronous primaries. The goal of this study was to provide a more complete representation of multiple cancer risk in squamous cell carcinoma of the anus (SCCA) patients. A single-institution retrospective study of 46 patients treated definitively for SCCA between January 2006 and July 2017 was conducted. Of the 46 patients, 18 (39%) had either a primary malignancy before SCCA (n=9) or SPM after an index SCCA (n=9). Six patients had ≥3 total malignancies. In our cohort, patients without SPMs tended to die from SCCA recurrence, while patients with SPMs were more likely to die from their SPM than from SCCA. Our study suggests that patients with SCCA are often either survivors of previous cancers or develop later malignancies. Several risk factors may play a role including HPV infection, HPV-related or treatment-related immunosuppression, somatic mutations due to chemotherapy, and genetic factors. Patients with SCCA require lifelong surveillance given their elevated risk of malignancy. Future work should focus on identifying genomic or immunologic factors that may predispose SCCA patients to develop multiple primary malignancies.

Multiple primary malignancies in patients with anal squamous cell carcinoma.

Prior studies examining the risk of second primary malignancy (SPM) after a first primary cancer generally have used large datasets such as the Surveillance, Epidemiology, and End Results (SEER) registry and excluded survivors of previous primaries and developers of synchronous primaries. The goal of this study was to provide a more complete representation of multiple cancer risk in squamous cell carcinoma of the anus (SCCA) patients. A single-institution retrospective study of 46 patients treated definitively for SCCA between January 2006 and July 2017 was conducted. Of the 46 patients, 18 (39%) had either a primary malignancy before SCCA (n=9) or SPM after an index SCCA (n=9). Six patients had ≥3 total malignancies. In our cohort, patients without SPMs tended to die from SCCA recurrence, while patients with SPMs were more likely to die from their SPM than from SCCA. Our study suggests that patients with SCCA are often either survivors of previous cancers or develop later malignancies. Several risk factors may play a role including HPV infection, HPV-related or treatment-related immunosuppression, somatic mutations due to chemotherapy, and genetic factors. Patients with SCCA require lifelong surveillance given their elevated risk of malignancy. Future work should focus on identifying genomic or immunologic factors that may predispose SCCA patients to develop multiple primary malignancies.

Risk of secondary primary malignancies in multiple myeloma patients with or without autologous stem cell transplantation.

Outcomes for patients with multiple myeloma (MM) have improved through use of novel treatments, especially lenalidomide combined with autologous stem cell transplantation. However, because of their increased life expectancy, an increased risk of secondary primary malignancies (SPMs) has been observed in MM patients, particularly after lenalidomide maintenance in both transplant-eligible (TE) and transplant-ineligible (TI) patients. To evaluate the incidence and risk factors of developing SPMs, we identified 17 TE-MM and 12 TI-MM patients with SPMs among 211 TE-MM and 280 TI-MM patients, including seven TE-MM and four TI-MM patients with hematological malignancies and ten TE-MM and eight TI-MM patients with non-hematological cancers, respectively. The median follow-up time from diagnosis was > 4years. Multivariate analysis identified a history of high-dose cyclophosphamide use for peripheral blood stem cell harvest in TE-MM patients and > 65years of age at diagnosis, or a history of adriamycin, lenalidomide, or thalidomide use in TI-MM patients as independent risk factors for SPMs (P < 0.001). Patients with a history of lenalidomide use had a lower risk of death among both TE-MM (P = 0.0326) and TI-MM (P < 0.001) patients. The survival benefit of receiving lenalidomide outweighed the increased risk of SPMs in both TE-and TI-MM patients.

The impact of age at the time of radiotherapy for localized prostate cancer on the development of second primary malignancies

PurposeThere is a known increased risk of second primary malignancy (SPM) in patients with prostate cancer (CaP) treated with radiotherapy (RT). It is unclear how age at diagnosis influences the risk of SPMs. Materials and methodsUsing the 1973 to 2013 Surveillance, Epidemiology, and End Results Program, we studied the impact of age on SPMs (defined as a bladder or rectal tumor) after localized CaP treatment with radical prostatectomy (RP) or RT. SPM risk was compared using inverse probability of treatment weighting (IPTW)-adjusted cumulative incidence function and competing-risk proportional hazard models. Overall survival (OS) in patients with SPM was compared using Kaplan Meier and Cox regression analyses. ResultsA total of 579,608 patients met inclusion criteria, and 51.8% of the cohort was treated with RT. The 10- and 20-year cumulative incidences of competing risk (IPTW adjusted) of SPMs were 1.9% (95%CI = 1.8–1.9%) and 3.6% (95%CI = 3.4–3.7%) after RP vs. 2.7% (95%CI = 2.6–2.8%) and 5.4%(95%CI = 5.3–5.6%) after RT. IPTW-adjusted competing risk hazard ratio (HR) of SPM after RT compared to RP was increased in the entire cohort (HR 1.46; 95%CI = 1.39–1.53, P < 0.001) and was highest in the youngest patients: Age <55 HR = 1.83 (95% confidence interval [CI] = 1.49–2.24, P<0.001), Age 55 to 64 HR = 1.66 (95%CI = 1.54–1.79, P < 0.001), Age 65–74 HR = 1.41 (95%CI = 1.33–1.48, P < 0.001), Age ≥75 HR = 1.14 (95%CI = 0.97–1.35, P = 0.112). At 10 years, SPM-specific mortality occurred in 28.9% of patients treated with RT, though OS with SPM was worse in the youngest patients: Age <55 HR = 1.88 (95%CI = 1.25–2.81, P = 0.002), Age 55–64 HR = 1.60 (95%CI = 1.42–1.81, P < 0.001), Age 65–74 HR = 1.40 (95%CI = 1.30–1.52, P < 0.001), Age ≥ 75 HR = 1.27 (95%CI = 1.06–1.53, P = 0.009). All of the age categories had similar median follow-up times. ConclusionAt 10 years there is a 1.8% increased incidence of SPM after RT compared to RP, of which <30% of RT-treated patients with an SPM die as a result of a SPM. However, the risk of SPMs was greatest among younger men treated with RT for localized CaP, and this relationship could not be explained solely by follow-up time, latency time, or life expectancy. An improved understanding of those at the highest risk of SPMs may help tailor treatment and surveillance strategies.

Overall risk of second primary malignancies in patients with malignant melanoma: A national U.S. population-based study

Overall risk of second primary malignancies in patients with malignant melanoma: A national U.S. population-based study

Second primary malignancy after multiple myeloma-population trends and cause-specific mortality.

The management of multiple myeloma (MM) has evolved with the increased use of autologous haematopoietic cell transplantation (AHCT) and the introduction of new agents. AHCT and lenalidomide maintenance have been associated with increased risk of second primary malignancy (SPM). We iseutilised the Surveillance, Epidemiology and End Results 13 registries to analyse 9833 patients diagnosed at age <65 years for three eras: 1995-99 (pre-thalidomide, limited use of AHCT), 2000-04 (post-thalidomide, pre-lenalidomide and bortezomib, increased isautilisation of AHCT) and 2005-09 (post-lenalidomide and bortezomib, higher isautilisation of AHCT). Changes in risk of SPM were assessed by utilising standardised incidence ratio (SIR) and cause-specific risk of death. Cumulative incidence of SPM at 90months was 4·7%, 6·0% and 6·3% respectively, P=0·0008. SIR for haematological malignancies in years 1-5 increased, from 1·28 (95% confidence interval [CI] 0·47-2·78) in 1995-99 to 2·17 (95% CI: 1·27-3·48) in 2005-09, due to increased risk of acute leukaemias and lymphomas. A similar trend was observed in years 6-10. Overall mortality in patients with MM declined sharply over time due to declines in MM-associated and cardiovascular mortality with no increase in risk of death from SPM. The evolution of MM therapy is linked to population-level increase in risk with no discernible effect in death from SPM.

Abstract 1191: Differences in time to second primary malignancies: Development among patients with head and neck squamous cell carcinoma

Abstract Purpose: Second primary malignancies (SPMs) are the leading cause of death in survivors of head and neck squamous cell carcinoma (HNSCC). Patients with HNSCC are at increased risk of SPM. This is concerning since the number of survivors among these patients has been increasing. The human papillomavirus (HPV) has emerged as a distinct risk factor for oropharyngeal squamous cell carcinoma, which has different prognosis from classic tobacco/alcohol-associated HNSCC. We assessed the time to development of SPM in a large U.S. cohort of patients with an index HNSCC, comparing potentially-HPV-associated and non-HPV-associated HNSCC. Methods: This was a population-based cohort study of 109,512 patients with HNSCC in the Surveillance, Epidemiology, and End Results registry (2000-2014). HNSCC included were for invasive squamous cell carcinoma per the International Classification of Diseases for Oncology, third edition codes. SPM was defined as the first subsequent primary cancer occurring at least 2 months after first cancer diagnosis. Time to SPM development was calculated as the date of diagnosis of SPM minus 2 months after the index diagnosis date. The main exposure was HPV-relatedness, based on whether patients' first HNSCC was potentially-HPV-associated or non-HPV-associated. Adjusted Cox proportional hazards regression model was used to evaluate the differences in the time to development of SPM and HPV-relatedness, adjusting for age at diagnosis, sex, race, marital status, year of diagnosis of first cancer, stage, grade, and treatment. Results: Among the 109,512 patients with an index HNSCC, 12.3% developed SPM. Median time to SPM development overall was 31 months, for an index potentially-HPV-associated HNSCC patients was 32 months, and for an index non-HPV-associated HNSCC patients was 30 months. Patients diagnosed with an index non-HPV-associated HNSCC had a 36% higher risk of developing SPM (aHR=1.36; 95% CI: 1.38-2.53) compared with those with an index potentially-HPV-associated HNSCC. When sites were broken down further, compared to patients with oropharynx cancer, patients with hypopharynx (aHR=1.63; 95% CI: 1.50-1.77) had the higher risk of developing SPM, followed by oral cavity (aHR=1.40; 95% CI: 1.33-1.47), and larynx (aHR=1.27; 95% CI: 1.21-1.33) cancers. Patients had higher risk of developing SPM if they were 60-69 (aHR=2.49; 95% CI: 2.34-2.66) or ≥70 (aHR=2.82; 95% CI: 2.64-3.02) vs. 18-49 years, male (aHR=1.08; 95% CI: 1.04-1.13), black (aHR=1.23; 95% CI: 1.16-1.30) vs. white, and distant (aHR=1.15; 95% CI: 1.09-1.23) vs. localized tumor. Conclusion: Patients with an index non-HPV-associated-HNSCC were more likely to develop SPM compared to those with potentially-HPV-associated-HNSCC. Health care professionals may consider this during follow-up of patients with HNSCC. Citation Format: Eric Adjei Boakye, Paula Buchanan, Leslie Hinyard, Nosayaba Osazuwa-Peters, Mario Schootman, Jay F. Piccirillo. Differences in time to second primary malignancies: Development among patients with head and neck squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1191.

Incidence of Second Malignancy in Patients with Papillary Thyroid Cancer from Surveillance, Epidemiology, and End Results 13 Dataset.

Increased risk of second primary malignancy (SPM) in papillary thyroid cancer (PTC) has been reported. Here, we present the most updated incidence rates of second primary malignancy from original diagnosis of PTC by using the data from the Surveillance, Epidemiology, and End Results. In this cohort, 3,200 patients developed SPM, a substantially higher number than in the reference population of 2,749 with observed to expected ratio (O/E) of 1.16 (95% CI; 1.12–1.21). Bone and joint cancer had the highest O/E ratio of 4.26 (95% confidence interval [CI] 2.33–7.15) followed by salivary gland (O/E 4.15; 95% CI 2.76–6.0) and acute lymphocytic leukemia (O/E 3.98; 95% CI 2.12–6.8). Mean age at the diagnosis of SPM was 64.4 years old. Interestingly, incidence of colorectal cancer was lower in thyroid cancer survivors compared to general population (large intestine O/E 0.3; 95% CI 0.06–0.88, rectum O/E 0.6; 95% CI 0.41–0.85); however, this was not observed in patients who underwent radiation therapy. The incidence of SPM at all sites was higher during 2000–2012 compared to 1992–1999 (O/E 1.24 versus 1.10). Surprisingly, patients with micropapillary cancer had higher incidence of SPM than counterparts with a larger tumor in radiation group (O/E of 1.40 versus 1.15). O/E of all cancers were higher in males compared to females with O/E of 1.41 versus 1.17 during the period of 2000–2012. Diagnosis of PTC before age 50, especially at age 30–34, was associated with higher incidence of overall SPM (age 30–34; O/E 1.43; 95% CI; 1.19–1.71). Efficient monitoring strategies that include age at the time of thyroid cancer diagnosis, exposure to radiation, gender, and genetic susceptibility may successfully detect SPM earlier in the disease course. This is especially important given the excellent prognosis of the initial thyroid cancer itself.

Incidence and risk of second primary malignancy after an index potentially-human papillomavirus-associated cancer.

1593Background: Approximately 39,000 HPV-associated cancers are diagnosed annually in the US. Oncogenic HPV-infections are associated with virtually all cases of cervical, 95% of anal, 73% of oroph...

Risk and types of secondary primary malignancies in DLBCL survivors changes over time based on stage at diagnosis.

e19540Background: Previous studies have shown increased risk of second primary malignancies (SPM) after DLBCL treatment. Risk factors for and types of SPM that occur, stratified by stage of DLBCL a...

Trend of second primary malignancy in Hodgkin lymphoma.

e18713Background: Long term survivors of HL are at increased risk of second primary malignancy (SPM). We conducted this study to evaluate the trend of SPM after the diagnosis of HL over the last fo...

Risk-benefit of dexrazoxane for preventing anthracycline-related cardiotoxicity: re-evaluating the European labeling.

Dexrazoxane can prevent anthracycline-associated cardiotoxicity. However, in 2011, its use in children was contraindicated by the EMA over concerns of increased risk of infection, myelosuppression and second primary malignancies, and because its efficacy in children had not then been established. We review here the evidence published since 2011, which confirms that dexrazoxane is an effective cardioprotectant in children and adolescents, is not associated with an increased risk of second primary malignancies or excess early or late mortality and does not impair chemotherapy efficacy. Based on this evidence, the contraindication for children and adolescents requiring high doses of anthracyclines and at risk for cardiotoxicity was removed from the European labeling for dexrazoxane.