Risk Of Second Primary Malignancies Research Articles

ABCL-310 Triple Metachronous Malignancies in Primary Diagnosed Diffuse Large B-Cell Lymphoma Patient: A Case Report

Diffuse large B-cell lymphoma (DLBCL), the most common type of non-Hodgkin lymphoma (NHL), is known to be associated with increased risk of second primary malignancies (SPM). The occurrence of more than one type of cancer in a single patient is considered a rare finding, either appearing at the same time (synchronous) or subsequently (metachronous). This study is to present this interesting case of a male patient diagnosed with DLBCL, basal cell carcinoma (BCC), and adenocarcinoma of colon metachronously. A case report from May 2012 to January 2022. Oncology Unit/Oncology Center Mansoura University, Egypt. A 43-year-old male patient, HCV positive, diagnosed from splenectomy with DLBCL, Stage IV. In 2012, the patient received 8 cycles of CHOP protocol and achieved complete remission. In 2016, he presented with a face ulcer, which was excised with adequate safety margins, and histopathological examination revealed BCC. In 2017, he presented with acute abdomen. Computed tomography (CT) showed a well-defined soft tissue mass at the distal part of the ascending colon and hepatic flexure with signs of intestinal obstruction. The patient underwent right hemicolectomy and double barrel ileotransverse colostomy, and the histopathological examination revealed grade II adenocarcinoma, Stage IIa. Then, he received 6 cycles of adjuvant de Gramont regimen. After that, CT and colonoscopy were free. In 2019, he presented with B symptoms and right axillary lymphadenopathy; biopsy revealed NHL of large-cell type in favor of high-grade follicular lymphoma. After receiving 4 cycles of DHAP protocol, PET/CT was negative. Yet, he refused autologous stem cell transplantation. In 2021, he presented with cervical lymphadenopathy and tumor lysis syndrome. Biopsy showed DLBCL. The patient is 43 years old, male, HCV positive, underwent splenectomy, was diagnosed with DLBCL, and received chemotherapy. All of these are considered risk factors for SPM. The patient received supportive treatment, and 3 sessions of hemodialysis were done. He has been lost to follow-up since January 16th, 2022. DLBCL increases the risk of SPM mostly due to immune dysfunction, immunosuppression, and the mutagenic effects of chemotherapy. Hence, regular screening of DLBCL patients and survivors is recommended.

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

Prior studies report a greater incidence of second primary malignancy (SPM) among patients with myeloproliferative neoplasms, although the true risk in primary myelofibrosis (PMF) has not been elucidated. We utilized the Surveillance, Epidemiology, and End Results database to evaluate the risk of SPM in PMF patients and analyzed the effects of sociodemographic factors on the risk of SPM. Out of 5273 patients, 385 patients (7.30%) developed SPM. SPM occurred at SIR of 1.95 (95% CI 1.76–2.15) and AER of 149.01 per 10,000 population. A significantly higher incidence of melanoma (SIR 1.76, 95% CI 1.01–2.86), lymphoma (SIR 3.38, 95% CI 2.28–4.83), and leukemia (SIR 27.19, 95% CI 23.09-31.81) was observed. The risk was significantly higher in patients ≤60 years, males, chemotherapy recipients, within 5 years of PMF diagnosis, and for PMF diagnosed after 2009.

Association between radioactive iodine treatment for pediatric and young adulthood differentiated thyroid cancer and risk of second primary malignancies

Association between radioactive iodine treatment for pediatric and young adulthood differentiated thyroid cancer and risk of second primary malignancies

Association between postoperative radiotherapy for young-onset head and neck cancer and long-term risk of second primary malignancy: a population-based study

BackgroundSecond primary malignancy (SPM) represents the leading long-term cause of death among patients with index head and neck squamous cell carcinoma (HNSCC). We aimed to quantify the association between postoperative radiotherapy (PORT) and the risk of SPM development for index HNSCC among adolescent and young patients, who are particularly vulnerable to radiation-associated impacts due to their increased tissue susceptibilities and longer life expectancies.MethodsThis study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of 5 year survivors of index young-onset HNSCC from 1975 to 2011. The outcome of interest was SPM, a new, metachronous malignancy after the index HNSCC. Standardized incidence ratios (SIRs) and excess absolute risks (EARs) were used to quantify the PORT-associated risks externally, and relative risks (RRs) were estimated by the multivariate Poisson regression analysis to quantify the PORT-associated risks internally.ResultsOf the included 2771 5 year survivors with index young-onset HNSCCs, the receipt of PORT (37.6%) was associated with higher risk of SPMs (RR, 1.23; 95% CI 1.07 to 1.43). PORT-associated risks were elevated for the majority of sites, including head and neck (RR, 1.19; 95% CI 0.95 to 1.50) and lung (RR, 1.67; 95% CI 1.18 to 2.34). With regarding to the subsites of head and neck, RRs were above unity in oral cavity squamous cell carcinoma (SCC) (RR, 1.68; 95% CI 1.39 to 2.03) and laryngeal SCC (RR, 1.02; 95% CI 0.73 to 1.43). A relatively greater RR was observed for patients younger than 35 years (RR, 1.44, 95% CI 0.37 to 5.57) and those diagnosed with localized diseases (RR, 1.16, 95% CI 0.9 to 1.5). PORT-associated risks were increased remarkably after 15 years of follow-up (RR, 1.24; 95% CI 0.97 to 1.58).ConclusionsAn association was discovered between PORT treatment and increased long-term risk of SPM among patients with index young-onset HNSCC. The findings suggest long-term follow-up surveillance for these patients, particularly those with oral cavity SCC or laryngeal SCC.

The risk of developing second primary malignancies among colorectal cancer patients.

Background: The increasing number of young colorectal cancer (CRC) survivors has led to ongoing concerns about the risk of secondary primary malignancies (SPMs). Here, we intended to comprehensively explore the pooled standardized incidence rates (SIRs) for total and site-specific SPMs in CRC survivors with different restriction to lag period.Methods: Pubmed, Embase, Cochrane Library, and Web of science databases were searched to identify any studies reporting the SIRs of SPM following CRC until August 2021. Total and site-specific SIRs with different restriction to lag period were pooled using fixed/random effect models.Results: A total of 42 full-text publications with more than 1, 524, 236 CRC survivors and 166, 210 SPM patients were included in the meta-analysis. Pooled data showed an increased SIRs for all SPMs in CRC survivors with different restriction to lag period (no restriction to lag period, SIR = 1.15, 95% CI = [1.08–1.23]; 1-year lag, 1.16 [1.10–1.23]; 5-year lag, 1.18 [1.09–1.28]; 10-year lag, 1.24 [1.11–1.39]). The conclusions were consistent for neoplasms of colorectum, corpus uteri, and small intestine with different restriction to lag period. However, limited evidence was presented for associations between CRC survivors and SPM for prostate, breast (female), ovarian, stomach, urinary bladder, kidney, thyroid, bone and soft tissue.Conclusion: CRC survivors are associated with an increased risk of SPMs, especially neoplasms of colorectum, corpus uteri, and small intestine. Further studies should explore the risks for these neoplasms in CRC survivors, thus providing the reference for future follow-up care.

Second Primary Malignancies in Diffuse Large B-cell Lymphoma Survivors with 40 Years of Follow Up: Influence of Chemotherapy and Radiation Therapy

PurposePrevious studies have shown an increased risk of second primary malignancies (SPMs) in survivors of diffuse large B-cell lymphoma (DLBCL). Survivors live longer due to the intensification of and improvements in therapy; thus, we aimed to characterize SPM patterns in patients with DLBCL by treatment modality. Methods and MaterialsStandardized incidence ratio and absolute excess risk of SPMs were assessed in patients with primary DLBCL from 1975 to 2016 in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program. A subgroup analyses based on, sex, race, age at the time of diagnosis, latency, and treatment modality were performed. Propensity score-adjusted cumulative incidence curves were generated, stratified by treatment and accounting for death as a competing risk. ResultsIn total, 45,946 patients with DLBCL were identified with a mean follow up of 70 months. Overall, 9.2% of patients developed an SPM with a standardized incidence ratio of 1.23 (95% confidence interval, 1.20-1.27). There was no difference in SPM risk between men and women or Black and White patients. Patients age <25 years were particularly susceptible to the development of SPMs, with a risk 2.5 times greater than patients aged 50 to 74 years. Temporal patterns showed increasing risk of solid malignancies and decreasing risk of hematologic malignancies over time, with bladder cancer posing the greatest absolute excess risk of any cancer type after 15 years. Patients treated with radiation therapy (RT), chemotherapy (CT), and chemoradiation therapy (CRT) all had an increased risk of SPM development compared with the general population. The cumulative incidence of SPMs was the lowest in patients treated with RT and the highest when treated with CRT. In the modern treatment era, the cumulative incidence of SPM for patients treated with CT versus CRT was not significantly different. ConclusionsIn this large population-based study, we demonstrate unique SPM risk patterns based on age, latency, and treatment modality that have important implications for the treatment and screening of patients diagnosed with DLBCL.

P1225: SECONDARY PRIMARY MALIGNANCIES (SPM) AFTER HIGH-DOSE CHEMOTHERAPY (HDT) WITH AUTOLOGOUS STEM CELL TRANSPLANT (ASCT) FOR LYMPHOMA: A DANISH NATIONWIDE COHORT STUDY

Background: High-dose chemotherapy (HDT) with autologous stem cell transplant (ASCT) have resulted in more long-term lymphoma survivors. However, HDT-ASCT is potentially associated with an increased risk of secondary primary malignancies (SPM) leading to loss of lifetime for these patients. Aims: To investigate the risk and types of SPM in lymphoma patients treated with HDT-ASCT compared to the risk of malignancies in a matched background population and to explore risk factors for SPM in HDT-ASCT treated lymphoma patients. Methods: In a nationwide matched cohort study, The Danish Lymphoma Register was used to identify all adult patients treated with HDT-ASCT in Denmark between 2001-2017 for diffuse large B-cell lymphoma, Hodgkin lymphoma, peripheral T-cell lymphoma, or mantle cell lymphoma, excluding patients with other prior cancers. Patients were matched in a ratio of 1:5 to cancer-free comparators from the Danish background population. Malignancies were identified in the Danish National Patient Register using ICD-10 codes and compared between the two groups using the Aalen-Johansen estimator, Cox regression, and incidence rate ratios (IRRs). Results: A total of 856 HDT-ASCT treated lymphoma patients and 4,280 matched comparators were followed for a median of 8 years. The cumulative risk of SPM with death as competing risk was higher for patients compared to comparators with risks at 5, 10, and 15 years of 8.9% [95% confidence interval 6.9;11.0], 16.3% [13.3;19.3], and 20.1% [16.1;24.2] for patients compared to 4.8% [4.1;5.5], 10.5% [9.3;11.7], and 16.6% [14.6;18.5] for comparators (Fig. 1a). The crude hazard ratio (HR) of SPM among patients vs comparators was 2.26 [1.83;2.79]. After adjusting for sex, educational level (low/high), chronic obstructive pulmonary disease (COPD), and alcohol-related diseases (neurological, mental, cardiovascular, or chronic use), the HR was 2.50 [2.02;3.10]. Compared to comparators, patients had increased rates of non-melanoma skin cancer (IRR 3.47 [2.18;5.38]) and myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) (IRR 35.32 [15.73; 94.26]) (Table 1). Rates of other malignancies (oral, gastrointestinal, respiratory, breast, female- or male genital, urinary, soft tissue, and melanoma) were similar between the two groups. The 15-year cumulative risk of MDS/AML was 4.6% [2.8;6.3] for patients (Fig. 1c) and the median overall survival following secondary MDS/AML was only 7 months. In comparison, median overall survival was 40 months in a sex- and age matched background population with newly diagnosed MDS/AML (Fig. 1d). Risk factors for SPM in lymphoma patients were older age (HR 1.06 [1.04;1.08] per year) and COPD (HR 3.15 [1.16;8.57]). Prior therapy (number of lines, intensive chemotherapy, radiotherapy), time since diagnosis, Ann Arbor stage, performance status, alcohol-related disease, and education were not associated with SPM. Table 1. - Rates of SPM per 1,000 person-years in lymphoma patients and matched comparators Comparators Patients SPM type Rate Rate IRR IRR 95% CI Overall 11.35 24.77 2.18 1.76; 2.18 Hematological 0.45 7.74 17.05 9.5; 32.16 MDS/AML 0.18 6.41 35.32 15.73; 94.26 MDS 0.12 3.98 32.89 12.27; 113.84 AML 0.06 2.43 40.19 10.79; 259.78 Non-melanoma skin cancer 1.79 6.19 3.47 2.18; 5.38 Image:Summary/Conclusion: Lymphoma patients treated with HDT-ASCT have an increased risk of SPM compared to a matched background population, especially for non-melanoma skin cancer and MDS/AML. Risk factors for SPM in patients were older age and COPD. These findings are important in the light of new potential treatment alternatives, such as CAR-T.

P638: THE RISK OF SECOND PRIMARY MALIGNANCIES AND CAUSE-SPECIFIC MORTALITY AMONG PATIENTS WITH T-CELL PROLYMPHOCYTIC LEUKEMIA IN THE UNITED STATES: A POPULATION-BASED STUDY.

Background: T cell prolymphocytic leukemia (T-PLL) is a rare lymphoid malignancy, compromising 2% of mature lymphocytic leukemias. The T-PLL follows an aggressive clinical course with median survival of 7.5 months with conventional chemotherpay. In the era of targeted therapy with anti-CD52 antibody for patients with T-PLL, there is data lacking on the spectrum of second primary malignancies (SPMs) and cause-specific mortality. Aims: In this current study we aim to identify the risk of SPM and cause specific mortality in patients with T-PLL in the era of targeted therapies with anti-CD52 antibodies using a national registry from the United States. Methods: The incidence of SPMs and cause-specific mortality among two-month survivors of T-PLL, was estimated using the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)-13 registries. We included patients from 1992-2018 with ICD-O-3 code 9834/3 from the registry. We estimated the risk of SPMs using standardized incidence ratios (SIRs) and cause-specific mortality by standardized mortality ratios (SMRs) and absolute excess risk (AER)/10,000 population. Results: We included a total of 314 patients with T-PLL in this study. The median age at diagnosis was 68.5 years (range 1-85 years). The median follow-up duration was 12 months (range 0-196 months). A total of 13 (4%) patients developed 14 SPMs at the last follow-up. The SPM risk for the cohort was significantly elevated (SIR 2.54, 95% confidence interval [CI] 1.39-4.27) compared with general population. The median latency period for SPM development was 28 months (range 8-108 months). The SIR was significant among males (SIR 2.96, 95% CI 1.42-5.44), but not in females (SIR 1.88, 95% CI 0.51-4.82). The SIR according to age groups was significant in patients with age < 60 years (SIR 3.84, 95% CI 1.25-8.97), but not in age > 60 years (SIR 2.14, 95% CI 0.98-4.06). Specific SPMs with the highest risk included nasopharyngeal cancers (SIR 200.87, 95% CI 5.09-1,119.20) and multiple myeloma (SIR 33.39, 95% CI 6.89-97.58). At last follow-up, 155 (49%) patients had died, of which 89% were due to malignant neoplasms. There was statistically significant risk of mortality due to all malignant cancers combined (SMR 58.35, 95% CI 49.03-68.94), largely due to mortality from lymphocytic leukemia (SMR 2587, 95% CI 2021-3264, AER 1757), non-Hodgkin lymphoma (SMR 100, 95% CI 45.88-190.45, AER 220), stomach and duodenal ulcers (SMR 73.74, 95% CI 1.87-410.84, AER 24.43), uterine cancer (SMR 66.55, 95% CI 1.68-370.78, AER 24.39), and pneumonia and influenza (SMR 11.88, 95% CI 2.45-34.71, AER 68.04). The risk of death from lymphocytic leukemia was highest within the first year of diagnosis of T-PLL and continued to decline slowly thereafter, although it remained statistically significantly elevated more than other causes of death (SMR 1yr=3405, AER 2666; SMR 1-5 yrs=2623, AER 1715; SMR 5-10 yrs=1015, AER 516). Summary/Conclusion: Our study reveals that the risk of developing SPMs remains elevated in patients with T-PLL compared to the general population. Additionally, men are at an increased risk for SPMs compared to women. Despite therapeutic advances in T-PLL, hematologic neoplasms (including lymphocytic leukemia) have remained the leading cause of death in the last three decades. Further studies are needed to better define the healthcare needs of T-PLL patients beyond initial treatment to reduce the burden of mortality from T-PLL and other SPMs.

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

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

Changing patterns of second primary malignancies and cause-specific mortality among patients with major salivary glands cancers in the United States: A population-based study.

e18081 Background: Salivary gland neoplasms are rare entities that comprise approximately 5% of all head and neck malignancies. The incidence of major salivary gland (MSG) cancers has increased about 54% from 1970 to 2000 in the United States (US). We undertook this study to investigate the risk of second primary malignancies (SPMs) and cause-specific mortality (CSM) in patients with MSG cancers using a national registry from the US. Methods: We estimated the incidence of SPMs among two-month survivors of MSG cancers using the Surveillance, Epidemiology, and End Results (SEER)-18 registries between 2008 to 2018. The risk of SPMs were calculated using standardized incidence ratios (SIRs) and the CSM by standardized mortality ratios (SMRs) and absolute excess risk (AER)/10,000 population. Results: We included 845 patients with MSG cancers in this study. The median age of diagnosis was 67 yrs (range 0 - 85 yrs). The median follow-up duration was 24 months (range 0 - 130 months). The median latency period for SPM development was 30 months (range 4 - 117 months). A total of 38 (4.5%) patients developed 41 SPMs at last follow-up. The SPM risk for cohort was significantly elevated (SIR = 1.81, 95% confidence interval [CI] = 1.30 - 2.46) compared with general population. The SPM risk was statistically higher among males (SIR = 2.42, 95% CI = 1.66 - 3.42) but not significant in females (SIR = 0.95, 95% CI = 0.44 - 1.81). Specific sites with highest SPMs risk included tonsil (SIR = 52.45, 95% CI = 1.33 - 292.22) followed by oral cavity (SIR = 15.55, 95% CI = 7.11 - 29.52). The risk for tonsil cancers were high from 5 to 10 years of initial diagnosis. While risk for oral cavity cancers, remained high throughout follow-up period. At the last follow-up, 214 (25%) patients had died. There was statistically significant risk of mortality due to MSG cancers (SMR = 5,453.61, 95% CI = 4,385.34 - 6,703.41, AER = 517.87) and oral cavity cancers (SMR = 663.40, 95% CI = 537.97 - 809.29, AER = 557.41) (Table). Conclusions: Our study concludes that men with MSG cancers are at an increased risk for SPMs compared to women. The risk of specific SPMs (tonsil and oral cavity cancers) was high even after a long period from the initial diagnosis of MSG cancers. This highlights the need for long-term surveillance in these patients for SPMs development.[Table: see text]

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

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

Risk of second primary malignancies among appendiceal cancer survivors in the United States.

e15514 Background: Appendiceal cancer (AC) survival rates have improved over the last decade. The risk of second primary malignancy (SPM) in AC survivors has become an important concern. Therefore, this study aimed to estimate the risk of SPM in patients with primary AC. Methods: We performed a retrospective cohort study of patients ≥18 years of age diagnosed with AC between 2000-2016 using data extracted from the United States Surveillance, Epidemiology, and End Results (SEER) database. The study endpoint was the occurrence of SPM diagnosed after two months of the index AC. We calculated the standardized incidence ratio (SIR) with 95% confidence intervals (CI) for SPM in AC survivors by using the SEER software. Results: Of 9578 patients with AC, 598 (6.2%) developed a SPM. The overall risk of SPM for all sites was significantly increased in AC patients (SIR = 1.46, 95% CI 1.34-1.58). The highest risk of developing a SPM was seen in ages &lt; 60 years, females, and Asian/Pacific Islanders, respectively (SIR = 1.84, 95% CI 1.64-2.07; SIR = 1.55, 95% CI 1.38-1.74; SIR = 1.72, 95% CI 1.12-2.52). The SPM sites associated with increased incidences included the small intestine, followed by the appendix, splenic flexure of the colon, and peritoneum/omentum/mesentery. There was an increased risk of developing non-Hodgkin lymphoma, but no elevated risk with developing second leukemias. Surgery and chemotherapy were associated with an increased incidence risk of SPM, respectively (SIR = 1.45, 95% CI 1.33-1.57; SIR = 1.47, 95% CI 1.25-1.71). Conclusions: AC survivors have an increased incidence of developing SPM, most notably in the small intestine, which suggests a pathophysiological process affecting derivatives of similar embryological origin. Long-term surveillance for SPM is recommended for AC survivors, especially those at high risk.[Table: see text]

Risk of second primary malignancies among patients with nasopharyngeal cancer in the United States: A population-based study.

e18056 Background: Nasopharyngeal cancers (NPCs) have an estimated incidence of 0.5 to 2 cases per 100,000 in the United States. Treatment of NPC with combination chemoradiotherapy has resulted in an 18% increase in 5-year overall survival in the US. It is essential to focus on the developments of second primary malignancies (SPMs) with improved survival. We aim to analyze the risk of SPMs among NPC survivors in this study. Methods: We estimated the incidence of SPMs among two-month survivors of NPC using the Surveillance, Epidemiology, and End Results (SEER)-18 registries between 2006 to 2018. The risk of SPMs was calculated using standardized incidence ratios (SIRs). Results: We included 7,560 patients with NPC in this study. The median age of diagnosis was 56 yrs (range 0 to 85 yrs). The median follow-up duration was 33 months (range 0 to 155 months). The median time for SPM development from initial diagnosis was 41 months (range 2 to 140 months). A total of 367 (5%) patients developed 398 SPMs at the last follow-up, of which 89% were solid organ malignancies, and 11% were hematologic neoplasms. The SPM risk for cohort was significantly elevated (SIR = 1.88, 95% confidence interval [CI] = 1.7 to 2.07) compared with the general population. The SIR was slightly higher in males (SIR = 1.90, 95% CI = 1.69 to 2.13) compared to females (SIR = 1.81, 95% CI = 1.48 to 2.20). The SIR according to age groups were as follows: age &lt; 65 years (SIR = 2.03, 95% CI = 1.79 to 2.29), age &gt; 65 years (SIR = 1.65, 95% CI = 1.38 to 1.94). Sites with highest risk included the nose, nasal cavity, and middle ear (SIR = 22.98, 95% CI = 9.92 to 45.27), nasopharynx (SIR = 17.28, 95% CI = 8.93 to 30.19), oral cavity and pharynx (SIR = 10.07, 95% CI = 7.81 to 12.79), esophagus (SIR = 3.97, 95% CI = 1.9 to 7.29), lung and bronchus (SIR = 3.53, 95% CI = 2.86 to 4.32), and liver (SIR = 3.05, 95% CI = 1.86 to 4.71) (Table). The risk of malignancies of the esophagus and lung were higher within the first year of diagnosis of NPC. The risk of malignancies of the nasopharynx, oral and nasal cavity, and liver was higher after one year of latency and remained statistically significantly elevated throughout the follow-up period. Conclusions: Our study reveals that patients with NPC are at higher risk of SPMs than the general population, most notably in the oral and nasal cavity, nasopharynx, esophagus, and lungs. These patients may benefit from cancer-specific screening during follow-up.[Table: see text]

Impact of second primary malignancy post-autologous hematopoietic stem cell transplantation on outcomes of multiple myeloma: A CIBMTR analysis.

8057 Background: Following autologous hematopoietic stem cell transplant (auto HCT), maintenance therapies improve survival, reduce relapse risk in multiple myeloma (MM), and are the de facto standard-of-care. However, clinical trials have shown an increased risk of second primary malignancies (SPM) with maintenance therapy, including second hematological malignancies (SHM). We examined data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry to evaluate the impact of SPM on progression-free (PFS) and overall survival (OS) and the utilization of allogeneic HCT in patients with therapy-related myeloid neoplasms (t-MN). Methods: Adult patients (pts) with MM who underwent first auto HCT in the United States with a melphalan conditioning regimen from 2011-2018 and subsequently received maintenance therapy were included (N=3948). The primary endpoint of interest was the impact of SPM and SHM on OS. Multivariate analytic (MVA) modelling was applied, accounting for competing risks while integrating significant covariates to determine the impact of SPM on PFS and OS. Finally, we studied the utilization and survival following allogeneic HCT for SHM. Results: Baseline characteristics were similar between the two groups. Maintenance regimens used were lenalidomide (2836, 72%), bortezomib (370,9 %) or lenalidomide + bortezomib (372, 9%) based combinations. At a median follow up of 37 months, 175 (5%) pts developed SPM, including 112 (64%) solid 36 (21%) myeloid, and 27 (15%) lymphoid cancers. In MVA, the development of SPM and SHM was associated with an inferior PFS (HR 2.62, P&lt;0.001 and HR 5.01, P&lt;0.001, respectively) and OS (HR 3.85, P&lt;0.001 and 8.13, P&lt;0.001, respectively). The two commonest causes of death were MM (42%) and SPM (30%) for those developing SPM. Similarly, MM (53%) and SHM (18%) were the two commonest causes of death for those developing SHM. Nine (14%,5 t-MDS and 4 t-AML) of 63 patients with SHM underwent an allogeneic HCT. Patients undergoing allogeneic HCT were more likely to have Karnofsky score ≥90 (100% vs. 50%, P=0.02) compared to those who did not. One year survival from allo SCT was 66.7% (CI 34.6-92%). Conclusions: The three-year cumulative incidence of SPM was 3.3 (2.6-4)% in this large contemporaneous CIBMTR cohort. Disease relapse remains the primary cause of death in MM patients who develop SPM or SHM. Given the median OS for MM is now &gt; 10 years, longer follow-up is needed to assess the SPM and SHM risks with maintenance therapy post-auto HCT.

Risk Prediction of Second Primary Malignancies in Primary Early-Stage Ovarian Cancer Survivors: A SEER-Based National Population-Based Cohort Study.

PurposeThis study aimed to characterize the clinical features of early-stage ovarian cancer (OC) survivors with second primary malignancies (SPMs) and provided a prediction tool for individualized risk of developing SPMs.MethodsData were obtained from the Surveillance, Epidemiology and End Results (SEER) database during 1998–2013. Considering non-SPM death as a competing event, the Fine and Gray model and the corresponding nomogram were used to identify the risk factors for SPMs and predict the SPM probabilities after the initial OC diagnosis. The decision curve analysis (DCA) was performed to evaluate the clinical utility of our proposed model.ResultsA total of 14,314 qualified patients were enrolled. The diagnosis rate and the cumulative incidence of SPMs were 7.9% and 13.6% [95% confidence interval (CI) = 13.5% to 13.6%], respectively, during the median follow-up of 8.6 years. The multivariable competing risk analysis suggested that older age at initial cancer diagnosis, white race, epithelial histologic subtypes of OC (serous, endometrioid, mucinous, and Brenner tumor), number of lymph nodes examined (<12), and radiotherapy were significantly associated with an elevated SPM risk. The DCA revealed that the net benefit obtained by our proposed model was higher than the all-screening or no-screening scenarios within a wide range of risk thresholds (1% to 23%).ConclusionThe competing risk nomogram can be potentially helpful for assisting physicians in identifying patients with different risks of SPMs and scheduling risk-adapted clinical management. More comprehensive data on treatment regimens and patient characteristics may help improve the predictability of the risk model for SPMs.

Second Primary Malignancies After Initial Cutaneous Angiosarcoma: A SEER population-Based Study

Introduction: The epidemiology of second primary malignancies is an under-investigated domain within dermatology. This notion is particularly true for more uncommon cutaneous oncologic diseases. While general epidemiological characteristics and survival data of patients with cutaneous angiosarcoma have been reported before, there is no investigation of the incidence and types of second primary malignancies (SPMs) that these patients face, which has relevance to screening and surveillance. &#x0D; Methods: The National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database was utilized in this study. Initial cases of CAS were extracted and analyzed using standardized incidence ratios (SIR) and excess absolute risks (EAR) for SPMs relative to a control population, which was matched by sex, race (white/unknown, black, other), age group (5-year interval), and calendar year (5-year interval). EAR was calculated per 10,000 persons. P-value &lt;0.05 was deemed statistically significant.&#x0D; Results: Compared to a matched cohort from the general population, patients with CAS demonstrated increased incidence of new malignancies (SIR 1.54; 95% CI, 1.05-2.17; EAR 107.02). Specifically, there was increased risk of soft tissue malignancies, and non-epithelial skin malignancies other than melanoma/basal cell/squamous cell.&#x0D; Discussion: SPMs may be linked to many etiologies, including genetic susceptibility, treatment-related sequelae, lifestyle/environmental factors, or shared risk factors. Indefinite treatments may induce SPMs. Recently, immunotherapy/immune-modulating drugs have been used to treat CAS4; this therapy may increase the risk of SPMs via immunosuppression. Shared etiology (i.e. blood vessel or soft tissue-derived neoplasms) may also explain SPMs observed. Importantly, CAS is associated with high recurrence even after complete resection.

Risk factors for second primary malignancies following thyroid cancer: a nationwide cohort study.

Thyroid cancer survivors have a high risk of second primary malignancies (SPMs). We aimed to evaluate the site-specific incidence, prognosis, and risk factors for metachronous SPMs following thyroid cancer. A nationwide cohort study. This study included data from the Korea National Health Insurance Service (between 2002 and 2018). Exposure to diagnostic radiation was defined by the number of computed tomography (CT) and positron emission tomography-CT scans after the index date. A cumulative radioactive iodine (RAI) dose >100 mCi was considered high-dose RAI. During the median 6 years of follow-up, among 291 640 patients, 13 083 (4.5%) developed SPMs. Thyroid cancer survivors had a 26% increased risk of SPMs compared with the general population (standardized incidence ratio: 1.26; 95% CI: 1.22-1.29). Furthermore, those with SPMs had a significantly poorer survival rate than those without SPMs (hazard ratio: 11.85; 95% CI: 11.21-12.54; P < 0.001). Significantly elevated risks were observed in myeloid leukemia and 13 solid cancer sites: lip, salivary gland, small intestine, larynx, lung, mediastinum and pleura, mesothelium, breast, corpus uteri, ovary, prostate, kidney, and bladder. Frequent diagnostic medical radiation exposure and high-dose RAI therapy were independent risk factors for several SPMs, including the cancer of salivary gland, lung, mediastinum and pleura, breast, kidney, and bladder, as well as myeloid leukemia. Frequent diagnostic radiation exposure and high-dose RAI therapy are independent risk factors for SPM following thyroid cancer. Clinicians need to consider minimizing unnecessary diagnostic radiation exposure and administering a high dose RAI only when justified in patients with thyroid cancer.

Second primary malignancy risk in thyroid cancer and matched patients with and without radioiodine therapy analysis from the observational health data sciences and informatics.

Risk of second primary malignancy (SPM) after radioiodine (RAI) therapy has been continuously debated. The aim of this study is to identify the risk of SPM in thyroid cancer (TC) patients with RAI compared with TC patients without RAI from matched cohort. Retrospective propensity-matched cohorts were constructed across 4 hospitals in South Korea via the Observational Health Data Science and Informatics (OHDSI), and electrical health records were converted to data of common data model. TC patients who received RAI therapy constituted the target group, whereas TC patients without RAI therapy constituted the comparative group with 1:1 propensity score matching. Hazard ratio (HR) by Cox proportional hazard model was used to estimate the risk of SPM, and meta-analysis was performed to pool the HRs. Among a total of 24,318 patients, 5,374 patients from each group were analyzed (mean age 48.9 and 49.2, women 79.4% and 79.5% for target and comparative group, respectively). All hazard ratios of SPM in TC patients with RAI therapy were ≤ 1 based on 95% confidence interval(CI) from full or subgroup analyses according to thyroid cancer stage, time-at-risk period, SPM subtype (hematologic or non-hematologic), and initial age (< 30years or ≥ 30years). The HR within the target group was not significantly higher (< 1) in patients who received over 3.7GBq of I-131 compared with patients who received less than 3.7GBq of I-131 based on 95% CI. There was no significant difference of the SPM risk between TC patients treated with I-131 and propensity-matched TC patients without I-131 therapy.

Risk of Second Primary Malignancies Associated with Radioactive Iodine Treatment in Young Patients with Thyroid Cancer

Risk of Second Primary Malignancies Associated with Radioactive Iodine Treatment in Young Patients with Thyroid Cancer

Use of Hypolipidemic Drugs and the Risk of Second Primary Malignancy in Colorectal Cancer Patients.

Simple SummaryHypolipidemic drugs are among the most frequently prescribed medications in the Western world. Since many studies have indicated their role in carcinogenesis, this work aimed to investigate their association with the occurrence of a second primary malignancy in colorectal cancer survivors. The overall incidence of a second neoplasm was not linked to hypolipidemic medication; however, a subgroup analysis revealed a lower incidence of secondary neoplasia in statin users. When stratified by cancer types, a significant increase in gastric and bladder cancer was detected among colorectal cancer patients using hypolipidemic drugs. Survival outcomes in patients with early-stage colorectal carcinoma who suffered second cancer were significantly worse if treated with hypolipidemic drugs. Although our results do not provide evidence for a causative relationship between hypolipidemic medication and carcinogenesis, these correlations might steer the direction of tertiary prevention care towards specific risk factors shared between cardiovascular diseases and cancer.An increasing number of studies has brought evidence of the protective role of statin use against different types of cancer. However, data on their association with second primary malignancies (SPMs) are lacking. The purpose of this study was to determine the role of hypolipidemic treatment in the prevention of second primary cancer in colorectal cancer (CRC) survivors. We conducted a retrospective single-institution study of 1401 patients with newly diagnosed colorectal cancer from January 2003 to December 2016, with follow-up until December 2020. An SPM was detected in 301 patients (21%), and the incidence was significantly lower in patients with statin medication. However, stratification by cancer types revealed an increased incidence of bladder and gastric cancer in hypolipidemic users. A Kaplan−Meier analysis of early-stage CRC survivors with an SPM showed a significant survival benefit in patients without a history of hypolipidemic treatment. Despite the protective role of statins on overall second cancer incidence, these data indicate that CRC survivors treated with hypolipidemic drugs should be screened more cautiously for SPMs, especially for gastric and bladder cancer.