Risk Of Second Primary Malignancies Research Articles

Risk of second primary malignancies in patients with chronic lymphocytic leukemia: a population-based study in the Netherlands, 1989-2019

The longevity of patients with chronic lymphocytic leukemia (CLL) has improved progressively over the past decades, making it essential to understand long-term health outcomes, such as second primary malignancies (SPMs). Therefore, this nationwide, population-based study assessed the risk of SPM development in CLL patients diagnosed during 1989-2019 in the Netherlands compared to the expected number of malignancies in an age-, sex-, and period-matched group from the general Dutch population. In 24,815 CLL patients followed for 162,698.49 person-years, 4369 SPMs were diagnosed with a standardized incidence ratio (SIR) of 1.63 (95% confidence interval [CI] 1.59–1.68). This elevated risk was observed for solid (SIR, 1.67; 95% CI, 1.65–1.75) and hematological SPMs (SIR 1.42; 95% CI, 1.24–1.62). The highest risk for SPMs was noted beyond five years post-diagnosis (SIR, 1.70; 95% CI, 1.62–1.77), for male individuals (SIR, 1.70; 95% CI, 1.64–1.77), and patients aged 18–69 years (SIR, 1.92; 95% CI, 1.79–2.05). The risk of SPMs was higher in CLL patients who received anti-neoplastic therapy (SIR, 2.12; 95% CI, 1.96–2.28), as compared with those who did not (SIR, 1.58; 95% CI, 1.53–1.63). Routine surveillance activities and tailored interventions to counteract the increased morbidity and excess mortality associated with SPMs are essential for improving long-term outcomes in CLL patients.

Incidence of second primary malignancies in women with different stages of breast cancer.

Breast cancer (BC) is the most common cancer in women worldwide. Because of the extended survival of patients with BC, the occurrence of second primary malignancies (SPMs) after BC is an important issue. We identified female patients with BC in the Breast Cancer Health Database of Taiwan, which includes four cancer registry datasets between 2002 and 2014 from Taiwan Cancer Registry. We compared the incidence of SPM between patients who received chemotherapy and/or radiotherapy with those who did not. Stratified analyses were performed according to the American Joint Committee on Cancer (AJCC) stage. The Cox regression model was used to identify the risk factors for SPM and evaluate their effects. We enrolled 85,947 eligible patients with BC, and 2,656 (3.09%) patients developed SPM. The median duration of SPM was 2.70 (1.14-5.14) years. Radiotherapy was administered in 40,946 (47.64%) patients, and chemotherapy was administered in 52,120 (60.64%). The most common SPMs were digestive tract cancers (876, 31.89%). The risk factors for SPM included the AJCC stage, chemotherapy, radiotherapy, age, and underlying comorbidities. Neither chemotherapy nor radiotherapy was associated with an increased risk of SPM in any stage. In contrast, after adjusting for other risk factors, patients at stage III/IV who received both therapies had lower risks of SPM compared with those who did not (p = 0.047). The risk of SPM was different across BC stages. Neither chemotherapy nor radiotherapy was associated with an increased risk of SPM in women with BC.

Association between radiotherapy and risk of second primary malignancies in patients with resectable lung cancer: a population-based study

BackgroundThe most common form of treatment for non-metastatic lung cancer is surgery-based combination therapy, which may also include adjuvant radiotherapy or chemotherapy. Second primary malignancies (SPMs) are uncommon but significant radiation side effects in patients with resectable lung cancer, and SPMs have not been adequately investigated. Our study aims to assess the correlations of radiotherapy with the development of SPMs in patients with resectable lung cancer.MethodsWe screened for any primary malignancy that occurred more than five years after the diagnosis of resectable lung cancer. Based on the large cohort of the Surveillance, Epidemiology and End Results database, radiotherapy-correlated risks were estimated using the Poisson regression analysis and the cumulative incidence of SPMs was calculated using Fine-Gray competing risk regression analysis.ResultsAmong the 62,435 patients with non-metastatic lung cancer undergoing surgery, a total of 11,341 (18.16%) patients have received radiotherapy. Our findings indicated that radiotherapy was substantially related to a high risk of main second solid malignancies (RR = 1.21; 95%CI, 1.08 to 1.35) and a negligible risk of main second hematologic malignancies (RR = 1.08; 95%CI, 0.84 to 1.37). With the greatest number of patients, the risk of acquiring a second primary gastrointestinal cancer was the highest overall (RR = 1.77; 95 percent CI, 1.44 to 2.15). The cumulative incidence and standardized incidence ratios of SPMs revealed similar findings. Furthermore, the young and the elderly may be more vulnerable, and the highest risk of acquiring most SPMs was seen more than ten years after lung cancer diagnosis. Additionally, more attention should be paid to the second primary gastrointestinal cancer in young individuals with resectable lung cancer.ConclusionAfter receiving radiotherapy, an increased risk of developing second primary solid and gastrointestinal cancers was observed for patients with resectable lung cancer. The prevention of SPMs associated with radiotherapy requires further attention.

Second primary malignancies in non-Hodgkin lymphoma: epidemiology and risk factors.

With the advancements in therapeutics for non-Hodgkin lymphoma (NHL), the long-term survival of patients with NHL has markedly increased. Second primary malignancies (SPMs) have become an increasingly relevant long-term concern for NHL survivors. The etiology of SPMs is multifactorial and involves multiple steps. Germline alterations, immune dysregulation, and clonal hematopoiesis contribute to the accumulation of intrinsic adverse factors, and external factors such as lifestyle; exposure to infectious factors; and late effects of radiotherapy, chemotherapy, high-dose therapy, and autologous hematopoietic stem cell transplantation further increase SPM risk. Therapy-related myeloid neoplasms (t-MNs) are a devastating complication of cytotoxic chemotherapeutic agents. However, as targeted therapies begin to replace cytotoxic chemotherapy, the incidence of t-MNs is likely to decline, particularly for indolent B-cell NHL.

Second Primary Malignancies of the Bones and Joints: More Common than Expected in Osteosarcoma Patients

Osteosarcoma is the most common primary bone tumor in children, adolescents, and young adults. Second primary malignancies (SPMs) are a potential serious long-term event that can occur in osteosarcoma survivors. The National Cancer Institute's Surveillance, Epidemiology, and End Results 18 database was queried for all osteosarcoma cases from 2000 through 2015. Standardized incidence ratio (SIR) and absolute excess risk (AER) of SPM per 10,000 persons (AER) relative to representative population-level data were calculated across for various anatomic locations. In total, 3438 patients with osteosarcoma were identified. Of these patients, 79 (2.3%) developed SPMs, with an SIR of 2.84 (95% confidence interval [CI] 2.35 to 3.39, P < 0.0001) and an AER of 44.96. The most common SPMs were tumors of the bones or joints (SIR 73.07, CI, 38.90 to 124.94, P < 0.0001, AER 7.48), tumors of soft tissues including the heart (SIR 15.19, CI, 5.58 to 33.07, P < 0.0001, AER 3.27), and leukemia (SIR 22.28, CI, 15.03 to 31.80, P < 0.0001, AER 16.74). The overall incidence of SPMs in osteosarcoma survivors was significantly higher than would otherwise be expected for this population. Considering the occurrence and targeting surveillance for SPM in the osteosarcoma patient population is warranted.

Risk and outcome of second primary malignancy in patients with classical Hodgkin lymphoma

Hodgkin lymphoma survivors demonstrated increased risk of secondary primary malignancies (SPMs), but comprehensive analysis of the risk and outcome of SPMs in classical Hodgkin lymphoma (cHL) patients has not yet been reported. Patients with cHL from 1975 to 2017 were identified from the Surveillance, Epidemiology and End Results (SEER) database. Standardized incidence ratios were calculated for the risk of solid and hematologic SPMs in cHL patients compared to the general population. The outcome of cHL patients developing SPMs were assessed by performing survival, competing risks regression, and cox proportional regression analyses. In a follow-up of 26,493 cHL survivors for 365,156 person years, 3866 (14.59%) secondary cancers were identified, with an standardized incidence ratio of 2.09 (95% CI: 2.02-2.15). The increased risk was still notable after follow-up of 10 years or more, and the risk is more pronounced for patients with female gender, younger age, advanced stage, chemotherapy, and radiation therapy. The overall survival is worse for cHL patients with SPMs after 11 years of follow-up (P < .0001). The main cause of death for cHL patients with SPMs is not cHL but other causes including SPMs. Multivariate Cox regression analysis confirmed SPMs as an independently adverse prognostic factor for cHL survivors (hazard ratio, 1.13; 95% CI, 1.05-1.21, P = .001). There is a significantly increased risk of developing SPMs for cHL survivors. The overall survival is worse for cHL patients and SPMs is an independent prognostic factor for cHL.

Incidence of Second Primary Malignancies in Lymphoma Survivors: A Prospective Cohort Study in the Modern Treatment Era

Background: Improved treatments for Hodgkin and non-Hodgkin lymphoma has resulted in a growing population of long-term survivors, many of whom are cured. A focus of long-term care of these patients (pts) has in turn moved toward optimizing survivorship, including identification and management of second primary malignancies (SPM). In this prospective cohort study initiated in the modern treatment era, we describe the incidence and factors associated with risk of SPM. Methods: Pts were identified from the Molecular Epidemiology Resource (MER) cohort of the University of Iowa/Mayo Clinic Lymphoma SPORE, which offers enrollment to all consecutive patients with newly diagnosed lymphoma aged 18+ years. Clinical and treatment data are abstracted from medical records using a standard protocol. Pts are prospectively contacted regularly to assess disease status and development of SPM. All reported SPM through 2021 were validated against medical records. For this analysis, SPM were defined as any cancer other than lymphoma diagnosed >90 days from lymphoma diagnosis. Cumulative incidence of SPM and 95% confidence intervals (CI) were calculated with death as a competing risk, and associations with patient and treatment characteristics were estimated with Cox models. To evaluate the incidence of SPM in the MER against expected population rates, we calculated the standardized incidence ratio (SIR) using the Iowa component of the Surveillance, Epidemiology and End Results (SEER) database, accounting for age, sex, calendar year and person-time. Results: Of 6929 pts enrolled into the MER from 9/2002 - 6/2015, 59% were male; median age at enrollment was 61 yrs (IQR: 51-70). 763 pts developed SPM through 2021, including 37 acute myeloid leukemia and myelodysplastic syndrome (AML/MDS), 341 non-melanoma skin, 133 genitourinary (GU), 57 gastrointestinal (GI), 49 breast, and 52 lung cancers. The 10-year cumulative incidence of SPM was 12% (CI: 11-13), and 31% (CI: 30-32) for the competing risk of death (Fig 1A). Skin cancers had highest 10-year cumulative incidence of 6.6% (CI: 5.9 -7.4), followed by GU 2.4% (CI: 2.0-2.9), breast 1.0% (CI: 0.8-1.4), lung 1.0% (CI: 0.8-1.3), GI 0.9% (CI: 0.7-1.3), and AML/MDS 0.7% (CI: 0.5-1.0)(Fig 1B). The MER cohort had a lower than expected rate of any SPM (excluding non-melanoma skin cancer, which SEER does not collect) compared to the general Iowa population (SIR=0.61, CI: 0.5-0.7), as well as lower than expected rates of GU (SIR=0.60, CI: 0.5-0.7), GI (SIR=0.45, CI: 0.3-0.6), breast (SIR=0.69, CI: 0.5-0.9), and lung (SIR=0.47, CI: 0.4-0.6) cancer. In contrast, the MER showed a 5-fold higher than expected rate of AML/MDS (SIR=5.2, CI: 3.6-7.1). Risk of SPM increased with age: compared to pts age 18-40 years, those 41-60 yrs had a 3-fold (CI: 1.9-4.5) and >60 yrs had a 6.3-fold (CI: 4.2-9.6) elevated risk of SPM. Females were at lower risk of SPM (HR=0.7, CI: 0.6-0.9). After adjustment for age and sex, there was no association with lymphoma subtype. For initial treatment class (adjusted for age, sex and subtype), risk of a SPM was associated with use of a systemic chemotherapy (HR=1.3, CI: 1.1-1.6); was inversely associated with initial observation (HR=0.8, CI: 0.6-0.9); and was not associated with use of local radiation (HR=0.9, CI: 0.7-1.2), an anthracycline (HR=1.0, CI: 0.8-1.3), alkylator (HR=1.2, CI: 1.0-1.4) or R-monotherapy (HR=1.0, CI: 0.7-1.3). In joint modeling of initial treatment adjusted for age, sex and subtype, compared to pts not receiving systemic chemotherapy, pts with systemic therapy including an alkylator but no anthracycline (HR=1.4, CI: 1.1-1.7) or systemic therapy without an alkylator or anthracycline (HR=1.3, CI:1.1-1.7) had increased risks of SPM, while those receiving both an alkylator/anthracycline were not at significantly elevated risk (HR=1.2, CI: 0.9-1.5). Conclusions: In the rituximab era, the cumulative incidence of any SPM increased over time and at 10 years after diagnosis was 12%, with about half of these due to non-melanoma skin cancers. While the cumulative incidence of AML/MDS at 10 years was low (0.7%), this represented a 5-fold excess risk over expected population rates, consistent with prior eras. In contrast, solid tumors were below expected population rates. Older age, male sex and systemic chemotherapy were associated with higher risk of SPM. Prevention and management of SPM continues to remain an important need for lymphoma survivors. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Epidemiology, Survival and Second Primary Malignancies in T-Cell Large Granular Lymphocytic Leukemia

Introduction T-Large Cell Granular Lymphocytic Leukemia (T-LGLL) is a rare lymphoproliferative disorder with an incidence of 2-3% of all mature lymphoid leukemias. Progressive/symptomatic T-LGLL which mainly presents with cytopenia's is very rare compared to the indolent forms. Given the rarity of the disease, limited literature is available about the epidemiology, survival, and development of secondary primary malignancies (SPMs) in T-LGLL. Methodology We used the November 2020 submission of the Surveillance, Epidemiology and End Results (SEER) 17 registry, which covers ~27.8% of the US population based on the 2010 census to identify all cases of T-LGL diagnosed between 2000-2019. We identified all cases using the International Classification of Diseases for Oncology edition 3 (ICD-O-3) code. Kaplan Meir method is used for survival analysis and standardized incidence ratio (SIR) or relative risk and absolute excess risk (AER) were calculated for SPM. This retrospective analysis was performed using SEER*Stat version 8.3.6 statistical software and STATA. Results A total of 2,297 cases were identified during the study period. The age-adjusted incidence rate of T-LGLL in the United States was 0.2 cases per 100,000 individuals. The incidence rate was higher in elderly patients (age >= 65 years) highest incidence was observed in 80-84 years. The median age of diagnosis was 66 years. Males were 52% (n= 1209) and females were 48% (n= 1093). Predominant race was Caucasians (81%) followed by Blacks 9.4%. The overall survival (OS) of the entire cohort at 1 year (yr), 3 yr, 5 yr was 92%, 84.8% and 80%. 5-yr OS was 77.2% in males and 82.6% in females. Caucasians had a 5-y OS of 78% and blacks had 88%. For SIR analysis, 1668 patients with T-LGLL as the primary malignancy were included. 139 (8.3%) patients developed SPM with a total of 151 SPMs. The median latency period for the development of SPMs was 25.5 (range= 5-209) months. T-LGLL patients had an overall increased risk of developing SPM than the general population (SIR= 1.48, 95% CI= 1.25-1.75, AER= 71.45, p< 0.05). Regarding solid tumors, this was predominantly observed in ovarian malignancy (SIR= 4.8, 95% CI= 1.5-10.7, AER= 5.72, p<0.05) followed by lung and bronchus (SIR= 1.88, 95% CI= 1.24- 2.74, AER= 18.55, p<0.05). Secondary hematological malignancies were predominantly lymphoma (SIR= 4.14, 95% CI = 2.5-6.5, AER= 21.09, p<0.05) and leukemia (SIR= 7, 95% CI= 4.3- 10.6, AER = 26.3, p<0.05) with acute lymphocytic leukemia (ALL) being the highest observed SPM (SIR= 31.3, 95% CI= 6.5- 91.5, AER = 4.25, p<0.05) (rest in table 1). The rate of overall SPM in T-LGLL after 1 yr (SIR= 8.2, 95% CI= 4.5-13.8, AER=98), 1- 5 yrs (SIR= 4.67, 95% CI= 2.99-6.94, AER= 49.92) and 10+ yrs (SIR= 2.84, 95% CI = 1.04-6.2, AER= 25.2) from diagnosis of T-LGLL was significantly higher than in the general population (all p<.05). This trend was not observed in the interval 5-10 yrs after diagnosis. Among T-LGLL patients, the risk of developing ALL was significantly higher within 1-yr after the diagnosis (SIR= 144.7, 95% CI= 13.9-414.2, ER= 15.8, p<0.05). The risk of development of solid tumor malignancies was significantly higher than the rest of the population only 10 yrs after the diagnosis of T-LGLL (SIR= 3.11, 95% CI = 1.6-5.77, AER= 285.11, p<0.05). Overall, tumors of lung and bronchus (17%), miscellaneous malignancies (10.6%), prostate (9.9%) were the most observed SPMs (Figure 1). Conclusion To our knowledge, this is the first comprehensive study assessing the incidence of SPMs in T-LGLL from a national database. The risk of SPM is higher in patients with T-LGLL compared to the general population especially 1 yr, 1- 5 yr, 10+ yrs from the diagnosis. The risk of secondary hematological malignancies, predominantly ALL and lymphoma is higher until 10 years from the diagnosis and the overall risk of secondary solid tumor malignancies are higher after 10 years from the diagnosis. T-LGLL patients also have a higher risk of developing lung, ovarian carcinoma compared to the general population. Our studies may help guide survivorship as close follow is needed for T-LGLL patients even after 5 and 10 years of diagnosis. Future studies are warranted to understand the reason for the increased development of SPM in T-LGLL patients and to specify the subtypes of secondary lymphoma's and ALL to understand the transformation pattern of T-LGL. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Incidence and Mortality of Second Primary Malignancies after Lymphoma

Introduction: Treatment for lymphoma has undergone significant transformation in the past decade with the introduction of novel treatment strategies. Given the long-term treatment and supportive care, patients with lymphoma are living longer under better disease control, and patients with lymphoma are at increased risk of developing second primary malignancies (SPMs). Herein, we estimated the incidence, risk factors, and outcomes in lymphoma survivors with SPMs. Methods: Patients diagnosed with SPMs after primary lymphoma in Shandong Provincial Hospital (SPH) from 2010 to 2021 were included. Additionally, the differences in the incidence and characteristics of SPMs across ethnic groups were delineated by comparing with the Surveillance, Epidemiology, and End Results (SEER) database. We calculated the risk of SPMs using standardized incidence ratio (SIR) and absolute excess risk (AER). Overall survival (OS) analysis was reported using the Kaplan-Meier method. Results: A total of 2,912 hospitalized lymphoma cases were included, and 63 patients (2.16%) had SPM during the follow-up. Of these patients, 44 (69.84%) were male and 19 (30.16%) were female. The median age was 61 years old (range 35-81) and the majority of patients diagnosed with SPMs were older (≥60 years old, 61.90%) and previously treated with chemotherapy (69.84%). Histopathologic subtypes of primary lymphoma were as follows: (1) Hodgkin's lymphoma (HL, 3.17%), (2) non-Hodgkin lymphoma (NHL, 80.96%), and (3) Unknown type (15.87%). Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and diffuse large B-cell lymphoma (DLBCL) were the most common subtypes. The median duration between SPMs and lymphoma was 3.14 years (range 0-9). The most common types of SPMs were digestive system tumors (27, 42.86%), respiratory system tumors (13, 20.63%), and urinary system tumors (8, 12.70%). Specifically, the common types of SPMs were lung (19.6%), stomach (10.7%), and liver (8.9%) (Fig. 1). In addition, 304,696 new lymphoma cases are diagnosed, as reported to SEER 18 registries from 2010 through 2018, and 13580 survivors (4.46%) had SPMs. As described above, these patients with SPMs were also mostly male and older when diagnosed with SPMs. The commonly diagnosed SPMs are NHL (17.7%), lung and bronchus cancer (12.1%), and prostate cancer (10.0%). Additionally, we showed that the incidence rate of SPMs after specific lymphoma in the SEER database was higher than that of the SPH database other than CLL (Fig. 2). Because the crude incidence rate of SPM was not adjusted for the expected number of lymphoma or the number of high-risk patients in a reference population, the SIR and AER of SPM were calculated in the further analysis. Among patients at lymphoma diagnosis, overall malignancy risk was significantly higher than expected in the U.S. general population after follicular lymphoma (FL, SIR=2.01; 95%CI 1.93-2.09), marginal zone lymphoma (MZL, SIR=1.78; 95%CI 1.68-1.88), HL (SIR=1.76; 95%CI 1.62-1.91), CLL/SLL (SIR=1.51; 95%CI 1.46-1.57) and DLBCL (SIR=1.45; 95%CI 1.39-1.5). Moreover, hematological malignancies (SIR=3.23; 95%CI 3-3.48) contributed more to the SPMs than solid-organ cancers (SIR=1.31; 95%CI 1.226-1.27) among these subtypes. In a multivariate analysis, most patients with SPMs were diagnosed at younger ages (<55 years) and found to be other (Asian or Pacific Islander, American Indian/Alaska Native) races. Additionally, a higher mortality rate is associated with advanced age, no rituximab-based chemotherapy, and latency (P<0.05). We found that OS is shorter for patients with SPMs compared with those without SPMs, with increasing divergence over time (P<0.00001). In further analysis, we compared the survival of the most common SPMs in people who were diagnosed with specific lymphoma. The results showed that lymphoma patients with NHL, urinary bladder, stomach, and lung cancer experienced worse survival compared with melanoma, thyroid, kidney, and breast cancer (P<0.00001). Conclusion: Our study illustrated the incidence, mortality, and related risk factors of SPMs in specific lymphoma survivors and showed that the incidence of SPMs after the lymphoma is higher in older men, particularly in lung cancer. We found an increased risk for lymphoma compared to the general population. More studies are needed to understand the molecular underpinning leading to increased SPM formation in lymphoma patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Incidence of Second Primary Malignancies (SPMs) in Patients in the US with Triple-Class-Exposed (TCE) Relapsed or Refractory Multiple Myeloma (RRMM)

Background Therapeutic advances have increased life expectancy for patients with RRMM. As survival has improved, SPMs have become an increasingly important safety consideration for RRMM patients. Prior studies have demonstrated that treatment with alkylators, autologous stem cell transplantation (ASCT), and immunomodulatory drugs (IMiDs), specifically lenalidomide, are associated with increased SPM risk. Patients who are TCE (exposure to ≥1 IMiD, ≥1 proteasome inhibitor [PI], and ≥1 anti-CD38 monoclonal antibody [mAb]) represent an increasingly large subgroup of RRMM patients. The objective of this study was to describe the incidence of SPMs in patients with TCE RRMM. These data may inform development and selection of novel treatments for these patients. Methods Data were from two large US health-insurance claims databases: the Optum Clinformatics® Data Mart and the IQVIA PharMetrics® Plus Health Insurance Claims database. TCE RRMM patients were selected if they had ≥1 confirmed diagnosis of multiple myeloma (MM) on or after December 1, 2015 (date of approval by the US Food and Drug Administration of 1st anti-CD38 mAb for RRMM) and evidence of being TCE. The first line of therapy (LOT) after becoming TCE was identified ("index LOT") and the date of initiation of this LOT was defined as the "index date". Patients who experienced SPMs prior to the index date were excluded. SPMs were identified based on having at least one inpatient or two outpatient diagnoses (of the same cancer type) of invasive malignancies or myelodysplastic syndromes (MDS) other than MM, Waldenstrom macroglobulinemia, plasma cell leukemia, non-melanoma skin cancers, or primary bone malignancies that were preceded by a diagnosis of bone metastases. The incidence of SPM was calculated per 100 person years (PY) of follow-up, considering only the first SPM for each patient. Cumulative incidence of SPM with death as competing risk was calculated for patients in Optum database (data on mortality was unavailable in the PharMetrics database). Results A total of 1,110 TCE RRMM patients were identified in the two databases, of whom 726 had no evidence of SPM prior the index date (Table). These 726 patients had a mean age of 66.6 y; 45% were female, with a mean of 3 prior LOTs and 3.2 years since diagnosis. Over a mean (SD) follow-up of 11.7 (10.4) months, 96 patients (14.8 per 100 PY) experienced a new SPM, including 47 (7.2 per 100 PY) with solid tumor and 51 (7.9 per 100 PY) with a hematologic malignancy. The latter included 22 (3.4 per 100 PY) with acute myeloid leukemia (AML) and 17 (2.6 per 100 PY) with myelodysplastic syndrome. Among patients in the Optum database (N=416), the cumulative incidence of SPM (95%CI) was estimated to be 10.3% (7.4% , 13.7%), 14.9% (10.8% , 19.6%), and 20.1% (13.9% , 27.2%) at 12, 24, and 36 months, respectively (Figure). Conclusions The incidence of SPM in TCE RRMM patients is clinically significant. Many SPMs in these patients are potentially serious malignancies, including AML and MDS. There is a need for effective treatments for TCE RRMM that are not associated with increased risks of SPMs. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Lenalidomide and risk of second primary malignancy—is disease context key?

The development of the immunomodulatory drug lenalidomide, along with proteasome inhibitors, has revolutionised the treatment of multiple myeloma since the early 2000s. Lenalidomide is now used in triplet or quadruplet combination therapeutic approaches for patients with newly diagnosed and relapsed myeloma. Lenalidomide has also been shown to prolong progression-free survival and overall survival as maintenance therapy after autologous haematopoietic stem-cell transplantation (HSCT). The approved indications for lenalidomide now include other haematological malignancies such as myelodysplastic syndrome with an isolated del(5q), mantle cell lymphoma, and follicular lymphoma.

Analysis and prediction of second primary malignancy in patients with breast cancer.

Second primary malignancy (SPM) is common in breast cancer (BC). The present study aimed to profile the characteristics of BC with SPM and to identify patients at high risk of SPM. Clinical and outcome data of BC cases were retrieved from the SEER database. Principal component analysis and a random forest model were utilized to create a model for predicting the occurrence of SPMs. Of the 286,047 BC cases analyzed, 9.32% developed SPMs. Approximately 70% of BCs that developed SPMs were ductal carcinoma and 71% of BCs that developed SPMs were human epidermal growth factor receptor 2 (HER2)-/hormone receptor (HR)+. The overall survival (OS) of the SPM cohort was significantly worse (hazard ratio: 1.49; 95% CI: 1.44-1.53; log-rank P<0.001). After adjusting for metastasis status, SPM was still a poor prognostic factor (hazard ratio: 1.71; 95% CI: 1.70-1.82; log-rank P<0.001). Of note, 50.5% of the SPMs occurred in the breast and the OS of the breast SPM group was significantly better than that of the other single-organ SPM group (hazard ratio: 0.46; 95% CI: 0.45-0.49; log-rank P<0.001) and the multiple-organ SPM group (hazard ratio: 0.44; 95% CI: 0.39-0.50; log-rank P<0.001). A random forest model created from clinical features predicted SPM with a positive predictive value of 32.3% and negative predictive value of 90.7% in the testing set. Thus, SPM occurs in nearly 1/10 of BC survivors and its existence and occurrence site significantly influence OS. SPM may be partly predicted from clinical features. In addition, it was indicated that postmenopausal elderly patients with a HER2-/HR+ molecular subtype should be more watchful and undergo screenings for SPMs.

Second Primary Malignancy Risk in Multiple Myeloma from 1975 to 2018.

Simple SummaryMultiple myeloma (MM) is the second most common hematological malignancy with median age of diagnosis between 65–70 years. Since the introduction of multiple novel agents in MM management, survival times of MM patients continue to improve. Longer survival in patients with MM may be associated with increased risks of developing second primary malignancies (SPM). In this study, we investigated the risk factors associated with SPM and survival among MM survivors from 1975 to 2018. Age, race, and sex were important factors for the risk of SPM. Moreover, after SPM development, MM patients had a statistically significant 1.4-fold increased risk of death than MM patients without SPM. Site- and time-specific surveillance strategies surveillance strategies should be recommended to monitor SPM in high-risk MM patients.As the survival times for multiple myeloma (MM) patients continue to extend, the risk of a second primary malignancy (SPM) among MM survivors has become a topic of increasing concern within the medical community. The Surveillance, Epidemiology, and End Results (SEER) 9 Registry Database was used to evaluate the risk and survival of SPM among MM survivors from 1975 to 2018. The standardized incidence ratio (SIR), absolute excess risk (AER), and cumulative incidence (CMI) of SPM for MM risk were calculated. Survival and the CMI were estimated by using hazard ratios (HRs). Subgroup analyses were performed according to race, sex, age, time of myeloma diagnosis, and the SPM site. A total of 43,825 cases were recorded with the initial diagnosis of MM from 1975 to 2018. A total of 3101 (7.1%) patients developed 3407 SPMs. Solid tumors were decreased in patients with MM (SIR = 0.93; 95% CI = 0.90–0.97) compared to the general population, whereas the risk of hematological malignancy was increased (SIR = 1.90; 95% CI = 1.72–2.10). Taking death as a competing event, the CMI of SPM in the whole population was 7.38% at 10 years (6.11% solid and 1.27% hematologic). Factors associated with SPM occurrence were age, sex, race, and time of MM diagnosis. The survival of SPM patients from MM diagnosis was longer than that of patients without SPM (HR = 0.67, 95% CI = 0.58–0.63). The median survival time was 17 months from SPM diagnosis and 34 months from MM diagnosis (HR = 1.4, 95% CI = 1.35–1.46). Age, race, and sex were important factors for the risk of SPM. Site- and time-specific surveillance strategies should be recommended to monitor SPM in high-risk MM patients.

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.