Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis
Introduction
Cancer is a devastating disease which poses major health burdens worldwide; there is an increasing incidence and mortality rate attributable to cancer annually. By 2022, the estimated number of cancer survivors is expected to reach 18 million in the United States (US).1 Several factors, including therapeutic approaches, could lead to long-term side effects. Given the advances in cancer screening and treatment, a greater number of patients survive with their tumors under control. Thus, understanding the long-term complications, such as the increased risk of second primary malignancies (SPM), is necessary to guide post-treatment surveillance in cancer survivors. The investigation of SPM has become more significant in recent years due to the increasing prevalence of cancer in younger patients, requiring increased public awareness and vigilance in screening programs.
Diffuse large B-cell lymphoma (DLBCL) represents the most common lymphoid malignancy in the western world. The standard therapy for advanced DLBCL is the R-CHOP regimen [rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone], and for limited-stage DLBCL, therapy entails R-CHOP with or without subsequent involved-field radiotherapy (IFRT).2., 3., 4. Overall, 50%-70% of patients could be cured using standard treatment5; one study found that the 10-year OS was greater than 40%.5 Given the favorable prognosis, adverse impact of SPM on survivors could be a pressing matter focused on among healthcare practitioners.6., 7. In this study, we determined the risk of SPM development in patients with DLBCL using the national Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database.
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Material and methods
Based on the US population-based SEER 9 Regs Custom Data, Nov 2016 Sub (1973-2014), we selected DLBCL patients diagnosed from January 1981 to December 2010. Cases diagnosed during an autopsy and those who were lost to follow-up were excluded. Considering the lack of uniformity and reliability of the World Health Organization (WHO) International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3),8., 9. we identified DLBCL cases according to the Lymphoma Subtype Recode/WHO 2008, which
Observed risk of second primary malignancies as compared with the general population
In total 34,254 patients were diagnosed with DLBCL as a primary malignancy in the SEER 9 registry, Nov 2016 Sub (1973-2014) from January 1981 to December 2010. Among these patients, 3751 (10.95%) patients with second cancers were identified, with a SIR of 1.19 (95% CI: 1.16-1.23, P < 0.05), and an AER of 27.24/10,000 person-years.
There was a significantly higher risk of tumors/malignancies in the following sites when compared with the general population: oral cavity and pharynx, hepatobiliary
Discussion
Previously, a large body of published literature has demonstrated the occurrence of SPM in HL; these previous studies indicated that HL patients are at high-risk for developing SPM.13., 14. Differing from HL, the standard front-line immunochemotherapy for DLBCL is the R-CHOP regimen. The role of consolidative radiotherapy in DLBCL treatment has been controversial especially concerning the overall survival of patients. In fact, increased risk of the development of specific SPMs has been observed
Conclusions
Taken together, our results offer insight into the occurrence of SPM in patients with DLBCL, indicating that the risks of certain types of neoplasms are increased, especially for patients under 45 years of age. Awareness of the increased risk of subsequent malignancies remains crucial for DLBCL survivors as well as for their physicians.
Declaration of Competing Interest
The authors declare that they have no conflict of interest.
Acknowledgments
The authors acknowledge the efforts of the SEER program tumor registries in the creation of the SEER database.
References (20)
- et al.
CHOP-like chemotherapy plus rituximab versus CHOP-like chemotherapy alone in young patients with good-prognosis diffuse large-B-cell lymphoma: a randomised con- trolled trial by the MabThera International Trial (MInT) Group
Lancet Oncol
(2006) - et al.
CHOP-like chemotherapy with or without rituximab in young patients with good-prognosis diffuse large-B-cell lymphoma: 6-year results of an open-label randomised study of the MabThera International Trial (MInT) Group
Lancet Oncol
(2011) - et al.
Long-term outcome of patients in the LNH-98.5 trial, the first randomized study comparing rituximab-CHOP to standard CHOP chemotherapy in DLBCL patients: A study by the Groupe d'Etudes des Lymphomes de l'Adulte
Blood
(2010) - et al.
Limitations and biases of the surveillance, epidemiology, and end results database
Curr Probl Cancer
(2012) - Cancer Survivorship, Atlanta (GA): Center for disease Control and Prevention (US), national Center for Chronic disease...
- et al.
CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma
N Engl J Med
(2002) - et al.
Long-term survival in Hodgkin's disease relative impact of mortality, second tumors, infection, and cardiovascular disease
Cancer J Sci Am
(1994) - et al.
Long-term survival and competing causes of death in patients with early-stage Hodgkin's disease treated at age 50 or younger
J Clin Oncol
(2002) - ICD-O-3: International Classification of Diseases for Oncology. 3. Geneva: World Health Organization; Available from...
- et al.
Expert review of non-Hodgkin's lymphomas in a population-based cancer registry: reliability of diagnosis and subtype classifications
Cancer Epidemiol Biomarkers Prev
(2004)
Cited by (14)
Second Primary Malignancies in Diffuse Large B-cell Lymphoma Survivors with 40 Years of Follow Up: Influence of Chemotherapy and Radiation Therapy
2022, Advances in Radiation OncologyCitation Excerpt :The long-term management of these patients can be challenging, because surveillance strategies are not well defined. Survivors of diffuse large B-cell lymphoma (DLBCL), the most common subtype of NHL, are susceptible to this increased risk of SPMs.5,6 A variety of risk factors have been implicated, including radiation therapy (RT), chemotherapy (CT), the use of anti-CD20 monoclonal antibodies (ie, rituximab), immunosuppression, demographics, and genetics.7-10
Survival among patients with composite and sequential lymphoma between primary mediastinal lymphoma/diffuse large B-cell lymphoma and classical Hodgkin lymphoma: A population-based study
2021, Leukemia ResearchCitation Excerpt :Due to the favorable prognosis and prior treatment, subsequent malignancies may be a major cause of death for DLBCL survivors. The risk of DLBCL survivors developing a secondary HL was 7.2 times higher compared with the general population [17]. However, few reports have described cHL after DLBCL/PMBCL, and the description has been limited to several cases [18,19].
Second primary neoplasms in patients with lung and gastroenteropancreatic neuroendocrine neoplasms: Data from a retrospective multi-centric study
2021, Digestive and Liver DiseaseCitation Excerpt :The association between NENs and SPMs has already been reported in the literature with various percentages, up to 55% [12], based on heterogeneous cohorts of patients with different follow-up. Herein, a 10% increased risk of developing SPM has been found, which is super-imposable to the risk of SPM observed in other non-neuroendocrine cancers [13,14] as well as to some series focused on NENs [15,16]. In a meta-analysis of 13 studies involving a total of 5280 NEN patients, 17% of them were associated with SPMs, a percentage at least twice as high compared to non-NEN primary neoplasms [12].
Second primary malignancies in non-Hodgkin lymphoma: epidemiology and risk factors
2023, Annals of Hematology