- Email: [email protected]
Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis
JID: YMCN
ARTICLE IN PRESS
[mUS1Ga;September 16, 2019;21:13]
Current Problems in Cancer xxx (xxxx) xxx
Contents lists available at ScienceDirect
Current Problems in Cancer journal homepage: www.elsevier.com/locate/cpcancer
Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis Shiyu Jiang a, Hongnan Zhen b, Hongxin Jiang c,∗ a
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China b Department of Radiation Oncology, Peking Union Medical College Hospital, Beijing, China c Department of Medical Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
a b s t r a c t Background: Previously, studies have shown increased risks of second primary malignancies (SPM) after Hodgkin lymphoma and non-Hodgkin lymphoma. Nevertheless, investigation quantifying risks of SPM in patients with diffuse large B-cell lymphoma (DLBCL) remains scarce. Methods: We used the US population-based SEER 9 Regs Custom Data, Nov 2016 Sub to analyze the risks of SPM in patients with DLBCL. The standardized incidence ratio (SIR), absolute excess risk (AER), and 95% confidence intervals (CIs) were calculated. Results: Among patients with DLBCL as a primary malignancy, 3751 patients had second cancer episodes identified, with a SIR of 1.19 (95% CI: 1.16-1.23, P < 0.05). There was a significantly higher risk of tumors/malignancies in the following sites of patients with DLBCL compared with the general population: Oral cavity and pharynx, hepatobiliary system, head and neck, thorax, bone and soft tissue, skin, breasts, urinary tract, and endocrine system. Additionally, leukemia, myeloma and lymphoma, and Kaposi sarcoma occurred more frequently in patients with DLBCL than in the general population. Risk for a subsequent colon/rectum/anus cancer, bone and joint malignancy, and melanoma were significantly elevated in DLBCL patients received beam radiation, while the risk for these malignancies was not significantly increased in those without a radiation record. Notably, for patients under 45 years of age, the risk for SPM was higher than their counterparts in other age groups. Conclusion: Our results offer insight into the occurrence of SPM among patients with DLBCL, suggesting awareness of the increased risk of subsequent malignancies is crucial for DLBCL survivors as well as for their physicians.
∗ Correspondence to: Hongxin Jiang, Department of Medical Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, 16 Baita Road West, Suzhou, 215001, China. E-mail address: [email protected] (H. Jiang).
https://doi.org/10.1016/j.currproblcancer.2019.100502 0147-0272/© 2019 Elsevier Inc. All rights reserved.
Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
ARTICLE IN PRESS
JID: YMCN
2
[mUS1Ga;September 16, 2019;21:13]
S. Jiang, H. Zhen and H. Jiang / Current Problems in Cancer xxx (xxxx) xxx
© 2019 Elsevier Inc. All rights reserved.
a r t i c l e
i n f o
Keywords: Diffuse large B-cell lymphoma; Second primary malignancy; Risk; SEER Program
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).2-4 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.
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 is updated for Hematopoietic codes on the basis of ICD-O-3 and the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2008).10 Furthermore, we selected patients who developed a SPM after the diagnosis of DLBCL. SPM was defined as a metachronous malignancy developing at least 6 months after DLBCL based on the Warren and Gates criteria.11 For the current study, age at diagnosis, Ann Arbor stage, receipt of radiotherapy (None/Unknown, beam radiation, or other) were collected. We used the multiple primary standardized incidence ratio (MP-SIR) session of the SEER stat software version 8.3.5 March 5, 2018 for statistical analysis. We calculated the standardized incidence ratio (SIR), absolute excess risk (AER), and 95% confidence interval (CI) for SPM in patients with DLBCL based on SPM subtypes, disease stage, and age. Subgroup analyses conducted in specific SPM subtypes, receipt of radiotherapy and age periods. We used the SIR proposed by the International Agency for Research on Cancer (IARC) to assess of the rate of second malignancies in patients with a given malignancy.12 The SIR estimate is the ratio of the observed (O) number of second cancer cases in the study group and the expected (E) number of second cancer cases in the general population, calculated using the standard rates provided by SEER∗ Stat. AER is an Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
ARTICLE IN PRESS
JID: YMCN
[mUS1Ga;September 16, 2019;21:13]
S. Jiang, H. Zhen and H. Jiang / Current Problems in Cancer xxx (xxxx) xxx
3
Table 1 Risk of second malignancy in patients with DLBCL reported in the SEER database between January 1981 and December 2010.
All sites Oral cavity and pharynx Liver, gallbladder, intrahepatic bile duct and other biliary Lung, bronchus, trachea, mediastinum and other respiratory organs Bones and joints and soft tissue Skin Genital system Female Male Urinary system Kaposi sarcoma Leukemia and myeloma Lymphoma Hodgkin lymphoma Non-Hodgkin lymphoma Endocrine system
Observed cases
Expected cases
SIR
P value
CI lower
CI upper
Absolute excess risk
3751 125 85
3140.96 72.01 65.8
1.19 1.74 1.29
P < 0.05 P < 0.05 P < 0.05
1.16 1.44 1.03
1.23 2.07 1.60
27.24 2.37 0.86
531
468.06
1.13
P < 0.05
1.04
1.24
2.81
38 178 653 141 512 355 46 230 312 59 253 71
19.24 136.41 708.55 137.54 571.01 279.56 3.73 136.78 141.76 8.19 133.57 37.21
1.97 1.30 0.92 1.03 0.90 1.27 12.34 1.68 2.20 7.20 1.89 1.91
P < 0.05 P < 0.05 P < 0.05 0.38 P < 0.05 P < 0.05 P < 0.05 P < 0.05 P < 0.05 P < 0.05 P < 0.05 P < 0.05
1.40 1.12 0.85 0.86 0.82 1.14 9.04 1.47 1.96 5.48 1.67 1.49
2.71 1.51 1.00 1.21 0.98 1.41 16.46 1.91 2.46 9.29 2.14 2.41
0.84 1.86 -2.48 0.15 -2.63 3.37 1.89 4.16 7.60 2.27 5.33 1.51
Abbreviations: SIR, standardized incidence ratio; CI, confidence interval.
absolute measure of the additional cancer occurrence in the study population. It is reported as the number of excess events per 10,0 0 0 person-years. Kruskal Wallis and Wilcoxon rank sum tests were used to compare the differences in the time to the development of a SPM based on the different cancer types.
Results 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 27.24/10,0 0 0 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 system, head and neck, thorax (lung, bronchus, trachea, mediastinum, and other respiratory organs), bone and soft tissue, skin, breasts, urinary tract, and endocrine system. Additionally, leukemia, myeloma and lymphoma, and Kaposi sarcoma occurred more frequently than in the general population (Table 1). Among hematological malignancies, leukemia and lymphoma were significantly increased with a SIR of 2.09 (P < 0.05, AER = 4.47) and 2.20 (P < 0.05, AER = 7.6), respectively. The risk of developing a non-Hodgkin lymphoma (NHL, SIR = 1.89, P < 0.05, AER = 5.33) was significantly higher in DLBCL survivors. Noticeably, the risk of developing a subsequent HL was greater than seven times (SIR = 7.20, P < 0.05, AER = 2.27) higher than in the general population. Acute myeloid leukemia (SIR = 4.29, P < 0.05, AER = 3.7) and chronic myeloid leukemia (SIR = 2.29, P < 0.05, AER = 0.68) were the most commonly occurring types of leukemia after primary DLBCL. Additionally, the incidence of acute lymphocytic leukemia (SIR = 3.46, P < 0.05, AER = 0.29) and acute monocytic leukemia (SIR = 10.35, P < 0.05, AER = 0.6) were significantly increased in patients previously diagnosed with DLBCL. Significant excess risk was also observed for bone and soft tissue tumors (SIR = 1.97, P < 0.05, AER = 0.84), oral cavity and pharynx cancer (SIR = 1.74, Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
JID: YMCN
4
ARTICLE IN PRESS
[mUS1Ga;September 16, 2019;21:13]
S. Jiang, H. Zhen and H. Jiang / Current Problems in Cancer xxx (xxxx) xxx
Fig. 1. Standardized incidence ratio according to different latency periods (2-11, 12-59, 60-119, 180-239, and 240+ months). The circles represent the standardized incidence ratios in the different time periods; only the solid circles indicate significant standardized incidence ratios.
P < 0.05, AER = 2.37), skin cancer (SIR = 1.30, P < 0.05, AER = 1.86), endocrine tumors (SIR = 1.91, P < 0.05, AER = 1.51), hepatobiliary malignancies (SIR = 1.29, P < 0.05, AER = 0.86), urinary cancer (SIR = 1.27, P < 0.05, AER = 3.37), and Kaposi sarcoma (SIR = 12.34, P < 0.05, AER = 1.89).
Relative excess risk according to follow-up interval Overall, the median duration from the diagnosis of DLBCL to SPM was 73.0 months; this significantly differed based on cancer types (P < 0.001). The median periods were 56.6, 61.0, 52.0, 78.0, and 115.0 months to the development of acute myeloid leukemia, HL, thyroid and thymus cancer, thoracic (lung, bronchus, trachea, mediastinum and other respiratory organs) cancer, and oral cavity and pharynx cancer, respectively. The risk for the development of a HL or acute myeloid leukemia after primary DLBCL was relatively high in the first decade and decreased in the subsequent decades, while the risk of oral cavity and pharynx cancer increased steadily with time (Fig. 1). Although the risk for SPM remained elevated after 20 years from the diagnosis of DLBCL (SIR for ≥ 20 years, 1.36, 95% CI, 1.18-1.56, P < 0.05, AER = 52.91), the SIR for most SPM remained statistically insignificant except for several subtypes: oral cavity and pharynx cancer (SIR = 3.42, 95% CI: 1.77-5.97, P < 0.05, AER = 8.31), urinary cancer (SIR = 1.99, 95% CI: 1.33-2.85, P < 0.05, AER = 14.11), and NHL (SIR = 2.33, 95% CI: 1.33-3.78, P < 0.05, AER = 8.93).
Relative excess risk according to radiotherapy and age A subgroup analysis was further performed to investigate the relationship of radiotherapy and SPM. We use primary site code C773 to select primary breast DLBCL and 9679/3 to select primary mediastinal (thymic) large B-cell lymphoma. No relationship was identified between radiotherapy and subsequent breast cancer in these two subtypes. However, risk for a subsequent colon/rectum/anus cancer (SIR = 1.22, P < 0.05, AER = 3.35), bone and joint malignancy (SIR = 7.35, P < 0.05, AER = 0.83) and melanoma (SIR = 1.44, P < 0.05, AER = 2.31) were significantly elevated in DLBCL patients received beam radiation, while the risk for these malignancies Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
ARTICLE IN PRESS
JID: YMCN
[mUS1Ga;September 16, 2019;21:13]
S. Jiang, H. Zhen and H. Jiang / Current Problems in Cancer xxx (xxxx) xxx
5
Table 2 Risk of second malignancy in patients with DLBCL based on age groups reported in the SEER database between January 1981 and December 2010.
15-44 years 45-54 years 55-64 years 65-74 years 75+ years All
None/Unknown Beam radiation None/Unknown Beam radiation None/Unknown Beam radiation None/Unknown Beam radiation None/Unknown Beam radiation None/Unknown Beam radiation
Observed cases
Expected cases
SIR
P value
CI lower
CI upper
223 179 385 167 645 267 739 333 489 248 2,487 1,195
124.04 75.28 269.29 133.06 516.82 229.17 699.94 308.88 493.21 228.5 2,104.19 975.2
1.80 2.38 1.43 1.26 1.25 1.17 1.06 1.08 0.99 1.09 1.18 1.23
P < 0.05 P < 0.05 P < 0.05 P < 0.05 P < 0.05 P < 0.05 0.10 0.17 0.39 0.18 P < 0.05 P < 0.05
1.57 2.04 1.29 1.07 1.15 1.03 0.98 0.97 0.91 0.95 1.14 1.16
2.05 2.75 1.58 1.46 1.35 1.31 1.13 1.20 1.08 1.23 1.23 1.30
Absolute excess risk 27.39 44.89 42.97 25.89 42.00 27.68 12.89 18.11 -2.12 20.77 26.23 30.06
Abbreviations: SIR, standardized incidence ratio; CI, confidence interval.
Fig. 2. Forest plot of the standardized incidence ratio of second primary malignancies according to radiation therapy in DLBCL patients in different age groups (15-44, 45-54, 55-64, 65-74 years and 75 years old). Confidence intervals are 95%.
were not increased in those without a radiation record. For patients who developed oral cavity and pharynx cancer after DLBCL, the SIR were 1.96 (95% CI: 1.42-2.63, P < 0.05, AER = 2.94) and 1.66 (95% CI: 1.32-2.07, P < 0.05, AER = 2.18) in those who underwent beam radiation and those without a radiation record, respectively. Likewise, for those who developed thyroid cancer after DLBCL, the SIR were 2.30 (95% CI: 1.24-2.39, P < 0.05, AER = 2.01) and 1.75 (95% CI: 1.50-3.37, P < 0.05, AER = 1.14) for those with or without radiation records, respectively. Additionally, we explored the risk of SPM in different age groups (Table 2). For patients under 45 years of age, the relative risk for SPM was significantly high, with a SIR of 1.92 (95% CI: 1.732.13, P < 0.05, AER = 30.07). Among them, those with a history of beam radiation in DLBCL treatment had more than twofold greater risk of developing SPM (SIR = 2.38, 95% CI: 2.04-2.75, P < 0.05, AER = 44.89). The SIR for patients 45-54 and 55-64 years of age were 1.35 (95% CI: 1.24-1.47, P < 0.05, AER = 34.07) and 1.15 (95% CI: 1.07-1.23, P < 0.05, AER = 24.59), respectively (Fig. 2). No excess risk was observed for patients over 65 years of age.
Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
JID: YMCN
6
ARTICLE IN PRESS
[mUS1Ga;September 16, 2019;21:13]
S. Jiang, H. Zhen and H. Jiang / Current Problems in Cancer xxx (xxxx) xxx
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 for NHL patients, such as cancers of the stomach, colorectum, and lungs; Nevertheless, data regarding SPM among DLBCL patients is relatively limited. Given the fact that DLBCL is a curable disease, long-term follow-up is not necessary until clinically indicated. Thus, it is essential to increase awareness of the late and long-term side effects associated with treatment. In the present study, we observed increased risks of SPM among DLBCL survivors, such as hematological malignancies, bone and soft tissue tumors, oral cavity and pharynx cancer, skin cancer, endocrine tumors, hepatobiliary malignancies, and urinary cancer. Specifically, we demonstrated the significant excess of risks of SPM in different age periods. We suppose SPM could potentially be cured if detected at an early stage, thus, clinicians should consider the possibility of SPM during follow-ups of DLBCL survivors. Patients with NHL have an increased risk of SPM that is not influenced by the histological NHL subtypes. Published literature has demonstrated excess risks for leukemia in DLBCL survivors without known HIV/AIDS.15 Likewise, our result regarding DLBCL were similar, which could be related to the application of DNA-damaging agents in the front-line treatment and genetic predisposition. Notably, we found an elevated risk for other malignancies which has not been reported in previous studies. This is most likely due to the larger sample size of our study. Additionally, SPM risks were strikingly different based on cancer subtypes, with the risk for HL significantly elevated, which is consistent with the finding from a previous study.15 Besides, the abovementioned treatment and genetic factors, environmental factors such as infection and smoking could contribute to SPM. In the present study, we observed a significantly high SIR for the development of Kaposi Sarcoma, which might be correlated with the incidence of HIV in HIV/AIDS-related DLBCL. Likewise, we assume that the excess risks of oral cavity and pharynx cancers were correlated with Epstein-Barr virus (EBV) and human papillomavirus (HPV).16,17 The risk of the development of SPM was elevated regardless of the age group, with the exception of those 65-74 years of age. The highest risk was observed for patients 15-44 years of age. This could be explained by the long-term interaction of external factors and individual predisposition such as the immunodysfunction of the patients themselves. Thus, both the DLBCL survivors and healthcare providers should be aware of SPM during follow-up visits or in the implementation of screening programs, especially for those under the age of 45 years. Earlier diagnosis of SPM in this population may assist in improving patients’ prognosis. The limitations in this study are those specific to the use of population-based registries. First, underestimation of radiotherapy may cause bias in the estimation of the correlation between SPM risk and radiotherapy. Second, some recurrences may have been categorized as SPM. However, migration of DLBCL patients out of a SEER catchment area may lead to an underestimation of second malignancies.18 Additionally, this population-based analysis lacks information regarding the anatomic site of DLBCL, radiation dose and fields, receipt of rituximab and chemotherapy as well as underreporting radiotherapy.19,20 Actually, some information relating to radiotherapy may be missed by SEER registries, especially for those patients receiving radiotherapy outside of hospital settings. All of the abovementioned factors limit the generalizability and validity of our findings.
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 Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
ARTICLE IN PRESS
JID: YMCN
[mUS1Ga;September 16, 2019;21:13]
S. Jiang, H. Zhen and H. Jiang / Current Problems in Cancer xxx (xxxx) xxx
7
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.
Supplementary material Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.currproblcancer.2019.100502.
References 1. Cancer Survivorship, Atlanta (GA): Center for disease Control and Prevention (US), national Center for Chronic disease Prevention and health Promotion. http://www.cdc.gov/cancer/survivorship/pdf/survivorship_fs.pdf (Accessed 23 May 2018). 2. Pfreundschuh M, Trümper L, Osterborg A, 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 controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7:379–391. 3. Pfreundschuh M, Kuhnt E, Trümper L, 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;12:1013–1022. 4. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–242. 5. Coiffier B, Thieblemont C, Van Den Neste E, 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;116:2040–2045. doi:10.1182/blood- 2010- 03- 276246. 6. Mauch P, Kalish L, Marcus K, et al. Long-term survival in Hodgkin’s disease relative impact of mortality, second tumors, infection, and cardiovascular disease. Cancer J Sci Am. 1994;1:33–42. 7. Ng AK, Bernardo MP, Weller E, 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;20:2101–2108. 8. ICD-O-3: International Classification of Diseases for Oncology. 3. Geneva: World Health Organization; Available from 20 0 0. 9. Clarke CA, Glaser SL, Dorfman RF, 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;13:138–143. 10. Sabattini E, Bacci F, Sagramoso C, et al. WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview. International Agency for Research on Cancer. Blood. 2008;102:83–87. 11. Warren S, Gates O. Multiple primary malignant tumors: a survey of the literature and a statistical study. Am J Cancer. 1932;16:1358–1414. 12. Breslow NE, Day NE, Davis W Statistical Methods in Cancer Research. Vol. 2. Lyon: International Agency for Research on Cancer; 1987. 13. Schaapveld M, Aleman BM, van Eggermond AM, et al. Second cancer risk up to 40 years after treatment for Hodgkin’s lymphoma. N Engl J Med. 2015;373:2499–2511. doi:10.1056/NEJMoa1505949. 14. Chowdhry AK, Mchugh C, Fung C, et al. Second primary head and neck cancer after hodgkin lymphoma : a population-based study of 44, 879 survivors of Hodgkin lymphoma. Cancer. 2015;121:1436–1445. doi:10.1002/cncr. 29231. 15. Morton LM, Curtis RE, Linet MS, et al. Second malignancy risks after non-hodgkin’s lymphoma and chronic lymphocytic leukemia: differences by lymphoma subtype. J Clin Oncol. 2010;28:4935–4944. doi:10.1200/JCO.2010.29.1112. 16. E.A. Engels, R.J. Biggar, H.I. Hall, et al: Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer 123(2008) 187–194. 17. Intaraphet S, Farkas DK, Johannesdottir Schmidt SA, et al. Human papillomavirus infection and lymphoma incidence using cervical conization as a surrogate marker: a Danish nationwide cohort study. Hematol Oncol. 2017;35:172–176. doi:10.1002/hon.2270. Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
JID: YMCN
8
ARTICLE IN PRESS
[mUS1Ga;September 16, 2019;21:13]
S. Jiang, H. Zhen and H. Jiang / Current Problems in Cancer xxx (xxxx) xxx
18. Park HS, Lloyd S, Decker RH, et al. Limitations and biases of the surveillance, epidemiology, and end results database. Curr Probl Cancer. 2012;36:216–224. doi:10.1016/j.currproblcancer.2012.03.011. 19. Curtis R, Freedman D, Ron E, et al.. New Malignancies Among Cancer Survivors: SEER Cancer Registries. Bethesda, MD: National Cancer Institute; 2006 1973-2000. NIH Pub. No. 05-5302. 20. Noone AM, Lund JL, Mariotto A, et al. Comparison of SEER treatment data with Medicare claims. Med Care. 2016;54:e55–e64. doi:10.1097/MLR.0 0 0 0 0 0 0 0 0 0 0 0 0 073.
Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
ARTICLE IN PRESS
[mUS1Ga;September 16, 2019;21:13]
Current Problems in Cancer xxx (xxxx) xxx
Contents lists available at ScienceDirect
Current Problems in Cancer journal homepage: www.elsevier.com/locate/cpcancer
Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis Shiyu Jiang a, Hongnan Zhen b, Hongxin Jiang c,∗ a
Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China b Department of Radiation Oncology, Peking Union Medical College Hospital, Beijing, China c Department of Medical Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou, China
a b s t r a c t Background: Previously, studies have shown increased risks of second primary malignancies (SPM) after Hodgkin lymphoma and non-Hodgkin lymphoma. Nevertheless, investigation quantifying risks of SPM in patients with diffuse large B-cell lymphoma (DLBCL) remains scarce. Methods: We used the US population-based SEER 9 Regs Custom Data, Nov 2016 Sub to analyze the risks of SPM in patients with DLBCL. The standardized incidence ratio (SIR), absolute excess risk (AER), and 95% confidence intervals (CIs) were calculated. Results: Among patients with DLBCL as a primary malignancy, 3751 patients had second cancer episodes identified, with a SIR of 1.19 (95% CI: 1.16-1.23, P < 0.05). There was a significantly higher risk of tumors/malignancies in the following sites of patients with DLBCL compared with the general population: Oral cavity and pharynx, hepatobiliary system, head and neck, thorax, bone and soft tissue, skin, breasts, urinary tract, and endocrine system. Additionally, leukemia, myeloma and lymphoma, and Kaposi sarcoma occurred more frequently in patients with DLBCL than in the general population. Risk for a subsequent colon/rectum/anus cancer, bone and joint malignancy, and melanoma were significantly elevated in DLBCL patients received beam radiation, while the risk for these malignancies was not significantly increased in those without a radiation record. Notably, for patients under 45 years of age, the risk for SPM was higher than their counterparts in other age groups. Conclusion: Our results offer insight into the occurrence of SPM among patients with DLBCL, suggesting awareness of the increased risk of subsequent malignancies is crucial for DLBCL survivors as well as for their physicians.
∗ Correspondence to: Hongxin Jiang, Department of Medical Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, 16 Baita Road West, Suzhou, 215001, China. E-mail address: [email protected] (H. Jiang).
https://doi.org/10.1016/j.currproblcancer.2019.100502 0147-0272/© 2019 Elsevier Inc. All rights reserved.
Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
ARTICLE IN PRESS
JID: YMCN
2
[mUS1Ga;September 16, 2019;21:13]
S. Jiang, H. Zhen and H. Jiang / Current Problems in Cancer xxx (xxxx) xxx
© 2019 Elsevier Inc. All rights reserved.
a r t i c l e
i n f o
Keywords: Diffuse large B-cell lymphoma; Second primary malignancy; Risk; SEER Program
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).2-4 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.
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 is updated for Hematopoietic codes on the basis of ICD-O-3 and the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2008).10 Furthermore, we selected patients who developed a SPM after the diagnosis of DLBCL. SPM was defined as a metachronous malignancy developing at least 6 months after DLBCL based on the Warren and Gates criteria.11 For the current study, age at diagnosis, Ann Arbor stage, receipt of radiotherapy (None/Unknown, beam radiation, or other) were collected. We used the multiple primary standardized incidence ratio (MP-SIR) session of the SEER stat software version 8.3.5 March 5, 2018 for statistical analysis. We calculated the standardized incidence ratio (SIR), absolute excess risk (AER), and 95% confidence interval (CI) for SPM in patients with DLBCL based on SPM subtypes, disease stage, and age. Subgroup analyses conducted in specific SPM subtypes, receipt of radiotherapy and age periods. We used the SIR proposed by the International Agency for Research on Cancer (IARC) to assess of the rate of second malignancies in patients with a given malignancy.12 The SIR estimate is the ratio of the observed (O) number of second cancer cases in the study group and the expected (E) number of second cancer cases in the general population, calculated using the standard rates provided by SEER∗ Stat. AER is an Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
ARTICLE IN PRESS
JID: YMCN
[mUS1Ga;September 16, 2019;21:13]
S. Jiang, H. Zhen and H. Jiang / Current Problems in Cancer xxx (xxxx) xxx
3
Table 1 Risk of second malignancy in patients with DLBCL reported in the SEER database between January 1981 and December 2010.
All sites Oral cavity and pharynx Liver, gallbladder, intrahepatic bile duct and other biliary Lung, bronchus, trachea, mediastinum and other respiratory organs Bones and joints and soft tissue Skin Genital system Female Male Urinary system Kaposi sarcoma Leukemia and myeloma Lymphoma Hodgkin lymphoma Non-Hodgkin lymphoma Endocrine system
Observed cases
Expected cases
SIR
P value
CI lower
CI upper
Absolute excess risk
3751 125 85
3140.96 72.01 65.8
1.19 1.74 1.29
P < 0.05 P < 0.05 P < 0.05
1.16 1.44 1.03
1.23 2.07 1.60
27.24 2.37 0.86
531
468.06
1.13
P < 0.05
1.04
1.24
2.81
38 178 653 141 512 355 46 230 312 59 253 71
19.24 136.41 708.55 137.54 571.01 279.56 3.73 136.78 141.76 8.19 133.57 37.21
1.97 1.30 0.92 1.03 0.90 1.27 12.34 1.68 2.20 7.20 1.89 1.91
P < 0.05 P < 0.05 P < 0.05 0.38 P < 0.05 P < 0.05 P < 0.05 P < 0.05 P < 0.05 P < 0.05 P < 0.05 P < 0.05
1.40 1.12 0.85 0.86 0.82 1.14 9.04 1.47 1.96 5.48 1.67 1.49
2.71 1.51 1.00 1.21 0.98 1.41 16.46 1.91 2.46 9.29 2.14 2.41
0.84 1.86 -2.48 0.15 -2.63 3.37 1.89 4.16 7.60 2.27 5.33 1.51
Abbreviations: SIR, standardized incidence ratio; CI, confidence interval.
absolute measure of the additional cancer occurrence in the study population. It is reported as the number of excess events per 10,0 0 0 person-years. Kruskal Wallis and Wilcoxon rank sum tests were used to compare the differences in the time to the development of a SPM based on the different cancer types.
Results 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 27.24/10,0 0 0 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 system, head and neck, thorax (lung, bronchus, trachea, mediastinum, and other respiratory organs), bone and soft tissue, skin, breasts, urinary tract, and endocrine system. Additionally, leukemia, myeloma and lymphoma, and Kaposi sarcoma occurred more frequently than in the general population (Table 1). Among hematological malignancies, leukemia and lymphoma were significantly increased with a SIR of 2.09 (P < 0.05, AER = 4.47) and 2.20 (P < 0.05, AER = 7.6), respectively. The risk of developing a non-Hodgkin lymphoma (NHL, SIR = 1.89, P < 0.05, AER = 5.33) was significantly higher in DLBCL survivors. Noticeably, the risk of developing a subsequent HL was greater than seven times (SIR = 7.20, P < 0.05, AER = 2.27) higher than in the general population. Acute myeloid leukemia (SIR = 4.29, P < 0.05, AER = 3.7) and chronic myeloid leukemia (SIR = 2.29, P < 0.05, AER = 0.68) were the most commonly occurring types of leukemia after primary DLBCL. Additionally, the incidence of acute lymphocytic leukemia (SIR = 3.46, P < 0.05, AER = 0.29) and acute monocytic leukemia (SIR = 10.35, P < 0.05, AER = 0.6) were significantly increased in patients previously diagnosed with DLBCL. Significant excess risk was also observed for bone and soft tissue tumors (SIR = 1.97, P < 0.05, AER = 0.84), oral cavity and pharynx cancer (SIR = 1.74, Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
JID: YMCN
4
ARTICLE IN PRESS
[mUS1Ga;September 16, 2019;21:13]
S. Jiang, H. Zhen and H. Jiang / Current Problems in Cancer xxx (xxxx) xxx
Fig. 1. Standardized incidence ratio according to different latency periods (2-11, 12-59, 60-119, 180-239, and 240+ months). The circles represent the standardized incidence ratios in the different time periods; only the solid circles indicate significant standardized incidence ratios.
P < 0.05, AER = 2.37), skin cancer (SIR = 1.30, P < 0.05, AER = 1.86), endocrine tumors (SIR = 1.91, P < 0.05, AER = 1.51), hepatobiliary malignancies (SIR = 1.29, P < 0.05, AER = 0.86), urinary cancer (SIR = 1.27, P < 0.05, AER = 3.37), and Kaposi sarcoma (SIR = 12.34, P < 0.05, AER = 1.89).
Relative excess risk according to follow-up interval Overall, the median duration from the diagnosis of DLBCL to SPM was 73.0 months; this significantly differed based on cancer types (P < 0.001). The median periods were 56.6, 61.0, 52.0, 78.0, and 115.0 months to the development of acute myeloid leukemia, HL, thyroid and thymus cancer, thoracic (lung, bronchus, trachea, mediastinum and other respiratory organs) cancer, and oral cavity and pharynx cancer, respectively. The risk for the development of a HL or acute myeloid leukemia after primary DLBCL was relatively high in the first decade and decreased in the subsequent decades, while the risk of oral cavity and pharynx cancer increased steadily with time (Fig. 1). Although the risk for SPM remained elevated after 20 years from the diagnosis of DLBCL (SIR for ≥ 20 years, 1.36, 95% CI, 1.18-1.56, P < 0.05, AER = 52.91), the SIR for most SPM remained statistically insignificant except for several subtypes: oral cavity and pharynx cancer (SIR = 3.42, 95% CI: 1.77-5.97, P < 0.05, AER = 8.31), urinary cancer (SIR = 1.99, 95% CI: 1.33-2.85, P < 0.05, AER = 14.11), and NHL (SIR = 2.33, 95% CI: 1.33-3.78, P < 0.05, AER = 8.93).
Relative excess risk according to radiotherapy and age A subgroup analysis was further performed to investigate the relationship of radiotherapy and SPM. We use primary site code C773 to select primary breast DLBCL and 9679/3 to select primary mediastinal (thymic) large B-cell lymphoma. No relationship was identified between radiotherapy and subsequent breast cancer in these two subtypes. However, risk for a subsequent colon/rectum/anus cancer (SIR = 1.22, P < 0.05, AER = 3.35), bone and joint malignancy (SIR = 7.35, P < 0.05, AER = 0.83) and melanoma (SIR = 1.44, P < 0.05, AER = 2.31) were significantly elevated in DLBCL patients received beam radiation, while the risk for these malignancies Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
ARTICLE IN PRESS
JID: YMCN
[mUS1Ga;September 16, 2019;21:13]
S. Jiang, H. Zhen and H. Jiang / Current Problems in Cancer xxx (xxxx) xxx
5
Table 2 Risk of second malignancy in patients with DLBCL based on age groups reported in the SEER database between January 1981 and December 2010.
15-44 years 45-54 years 55-64 years 65-74 years 75+ years All
None/Unknown Beam radiation None/Unknown Beam radiation None/Unknown Beam radiation None/Unknown Beam radiation None/Unknown Beam radiation None/Unknown Beam radiation
Observed cases
Expected cases
SIR
P value
CI lower
CI upper
223 179 385 167 645 267 739 333 489 248 2,487 1,195
124.04 75.28 269.29 133.06 516.82 229.17 699.94 308.88 493.21 228.5 2,104.19 975.2
1.80 2.38 1.43 1.26 1.25 1.17 1.06 1.08 0.99 1.09 1.18 1.23
P < 0.05 P < 0.05 P < 0.05 P < 0.05 P < 0.05 P < 0.05 0.10 0.17 0.39 0.18 P < 0.05 P < 0.05
1.57 2.04 1.29 1.07 1.15 1.03 0.98 0.97 0.91 0.95 1.14 1.16
2.05 2.75 1.58 1.46 1.35 1.31 1.13 1.20 1.08 1.23 1.23 1.30
Absolute excess risk 27.39 44.89 42.97 25.89 42.00 27.68 12.89 18.11 -2.12 20.77 26.23 30.06
Abbreviations: SIR, standardized incidence ratio; CI, confidence interval.
Fig. 2. Forest plot of the standardized incidence ratio of second primary malignancies according to radiation therapy in DLBCL patients in different age groups (15-44, 45-54, 55-64, 65-74 years and 75 years old). Confidence intervals are 95%.
were not increased in those without a radiation record. For patients who developed oral cavity and pharynx cancer after DLBCL, the SIR were 1.96 (95% CI: 1.42-2.63, P < 0.05, AER = 2.94) and 1.66 (95% CI: 1.32-2.07, P < 0.05, AER = 2.18) in those who underwent beam radiation and those without a radiation record, respectively. Likewise, for those who developed thyroid cancer after DLBCL, the SIR were 2.30 (95% CI: 1.24-2.39, P < 0.05, AER = 2.01) and 1.75 (95% CI: 1.50-3.37, P < 0.05, AER = 1.14) for those with or without radiation records, respectively. Additionally, we explored the risk of SPM in different age groups (Table 2). For patients under 45 years of age, the relative risk for SPM was significantly high, with a SIR of 1.92 (95% CI: 1.732.13, P < 0.05, AER = 30.07). Among them, those with a history of beam radiation in DLBCL treatment had more than twofold greater risk of developing SPM (SIR = 2.38, 95% CI: 2.04-2.75, P < 0.05, AER = 44.89). The SIR for patients 45-54 and 55-64 years of age were 1.35 (95% CI: 1.24-1.47, P < 0.05, AER = 34.07) and 1.15 (95% CI: 1.07-1.23, P < 0.05, AER = 24.59), respectively (Fig. 2). No excess risk was observed for patients over 65 years of age.
Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
JID: YMCN
6
ARTICLE IN PRESS
[mUS1Ga;September 16, 2019;21:13]
S. Jiang, H. Zhen and H. Jiang / Current Problems in Cancer xxx (xxxx) xxx
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 for NHL patients, such as cancers of the stomach, colorectum, and lungs; Nevertheless, data regarding SPM among DLBCL patients is relatively limited. Given the fact that DLBCL is a curable disease, long-term follow-up is not necessary until clinically indicated. Thus, it is essential to increase awareness of the late and long-term side effects associated with treatment. In the present study, we observed increased risks of SPM among DLBCL survivors, such as hematological malignancies, bone and soft tissue tumors, oral cavity and pharynx cancer, skin cancer, endocrine tumors, hepatobiliary malignancies, and urinary cancer. Specifically, we demonstrated the significant excess of risks of SPM in different age periods. We suppose SPM could potentially be cured if detected at an early stage, thus, clinicians should consider the possibility of SPM during follow-ups of DLBCL survivors. Patients with NHL have an increased risk of SPM that is not influenced by the histological NHL subtypes. Published literature has demonstrated excess risks for leukemia in DLBCL survivors without known HIV/AIDS.15 Likewise, our result regarding DLBCL were similar, which could be related to the application of DNA-damaging agents in the front-line treatment and genetic predisposition. Notably, we found an elevated risk for other malignancies which has not been reported in previous studies. This is most likely due to the larger sample size of our study. Additionally, SPM risks were strikingly different based on cancer subtypes, with the risk for HL significantly elevated, which is consistent with the finding from a previous study.15 Besides, the abovementioned treatment and genetic factors, environmental factors such as infection and smoking could contribute to SPM. In the present study, we observed a significantly high SIR for the development of Kaposi Sarcoma, which might be correlated with the incidence of HIV in HIV/AIDS-related DLBCL. Likewise, we assume that the excess risks of oral cavity and pharynx cancers were correlated with Epstein-Barr virus (EBV) and human papillomavirus (HPV).16,17 The risk of the development of SPM was elevated regardless of the age group, with the exception of those 65-74 years of age. The highest risk was observed for patients 15-44 years of age. This could be explained by the long-term interaction of external factors and individual predisposition such as the immunodysfunction of the patients themselves. Thus, both the DLBCL survivors and healthcare providers should be aware of SPM during follow-up visits or in the implementation of screening programs, especially for those under the age of 45 years. Earlier diagnosis of SPM in this population may assist in improving patients’ prognosis. The limitations in this study are those specific to the use of population-based registries. First, underestimation of radiotherapy may cause bias in the estimation of the correlation between SPM risk and radiotherapy. Second, some recurrences may have been categorized as SPM. However, migration of DLBCL patients out of a SEER catchment area may lead to an underestimation of second malignancies.18 Additionally, this population-based analysis lacks information regarding the anatomic site of DLBCL, radiation dose and fields, receipt of rituximab and chemotherapy as well as underreporting radiotherapy.19,20 Actually, some information relating to radiotherapy may be missed by SEER registries, especially for those patients receiving radiotherapy outside of hospital settings. All of the abovementioned factors limit the generalizability and validity of our findings.
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 Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
ARTICLE IN PRESS
JID: YMCN
[mUS1Ga;September 16, 2019;21:13]
S. Jiang, H. Zhen and H. Jiang / Current Problems in Cancer xxx (xxxx) xxx
7
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.
Supplementary material Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.currproblcancer.2019.100502.
References 1. Cancer Survivorship, Atlanta (GA): Center for disease Control and Prevention (US), national Center for Chronic disease Prevention and health Promotion. http://www.cdc.gov/cancer/survivorship/pdf/survivorship_fs.pdf (Accessed 23 May 2018). 2. Pfreundschuh M, Trümper L, Osterborg A, 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 controlled trial by the MabThera International Trial (MInT) Group. Lancet Oncol. 2006;7:379–391. 3. Pfreundschuh M, Kuhnt E, Trümper L, 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;12:1013–1022. 4. Coiffier B, Lepage E, Briere J, et al. CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. N Engl J Med. 2002;346:235–242. 5. Coiffier B, Thieblemont C, Van Den Neste E, 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;116:2040–2045. doi:10.1182/blood- 2010- 03- 276246. 6. Mauch P, Kalish L, Marcus K, et al. Long-term survival in Hodgkin’s disease relative impact of mortality, second tumors, infection, and cardiovascular disease. Cancer J Sci Am. 1994;1:33–42. 7. Ng AK, Bernardo MP, Weller E, 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;20:2101–2108. 8. ICD-O-3: International Classification of Diseases for Oncology. 3. Geneva: World Health Organization; Available from 20 0 0. 9. Clarke CA, Glaser SL, Dorfman RF, 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;13:138–143. 10. Sabattini E, Bacci F, Sagramoso C, et al. WHO classification of tumours of haematopoietic and lymphoid tissues in 2008: an overview. International Agency for Research on Cancer. Blood. 2008;102:83–87. 11. Warren S, Gates O. Multiple primary malignant tumors: a survey of the literature and a statistical study. Am J Cancer. 1932;16:1358–1414. 12. Breslow NE, Day NE, Davis W Statistical Methods in Cancer Research. Vol. 2. Lyon: International Agency for Research on Cancer; 1987. 13. Schaapveld M, Aleman BM, van Eggermond AM, et al. Second cancer risk up to 40 years after treatment for Hodgkin’s lymphoma. N Engl J Med. 2015;373:2499–2511. doi:10.1056/NEJMoa1505949. 14. Chowdhry AK, Mchugh C, Fung C, et al. Second primary head and neck cancer after hodgkin lymphoma : a population-based study of 44, 879 survivors of Hodgkin lymphoma. Cancer. 2015;121:1436–1445. doi:10.1002/cncr. 29231. 15. Morton LM, Curtis RE, Linet MS, et al. Second malignancy risks after non-hodgkin’s lymphoma and chronic lymphocytic leukemia: differences by lymphoma subtype. J Clin Oncol. 2010;28:4935–4944. doi:10.1200/JCO.2010.29.1112. 16. E.A. Engels, R.J. Biggar, H.I. Hall, et al: Cancer risk in people infected with human immunodeficiency virus in the United States. Int J Cancer 123(2008) 187–194. 17. Intaraphet S, Farkas DK, Johannesdottir Schmidt SA, et al. Human papillomavirus infection and lymphoma incidence using cervical conization as a surrogate marker: a Danish nationwide cohort study. Hematol Oncol. 2017;35:172–176. doi:10.1002/hon.2270. Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502
JID: YMCN
8
ARTICLE IN PRESS
[mUS1Ga;September 16, 2019;21:13]
S. Jiang, H. Zhen and H. Jiang / Current Problems in Cancer xxx (xxxx) xxx
18. Park HS, Lloyd S, Decker RH, et al. Limitations and biases of the surveillance, epidemiology, and end results database. Curr Probl Cancer. 2012;36:216–224. doi:10.1016/j.currproblcancer.2012.03.011. 19. Curtis R, Freedman D, Ron E, et al.. New Malignancies Among Cancer Survivors: SEER Cancer Registries. Bethesda, MD: National Cancer Institute; 2006 1973-2000. NIH Pub. No. 05-5302. 20. Noone AM, Lund JL, Mariotto A, et al. Comparison of SEER treatment data with Medicare claims. Med Care. 2016;54:e55–e64. doi:10.1097/MLR.0 0 0 0 0 0 0 0 0 0 0 0 0 073.
Please cite this article as: S. Jiang, H. Zhen and H. Jiang, Second primary malignancy in diffuse large B-cell lymphoma patients: A SEER database analysis, Current Problems in Cancer, https://doi.org/10.1016/j.currproblcancer.2019.100502