Skip to main content

Advertisement

SpringerLink
Log in

Development of second primary malignancy in patients with non-Hodgkin lymphoma: a nationwide population-based study

  • Original Article – Clinical Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Background

With the improved survival of non-Hodgkin lymphoma (NHL) patients, development of second primary malignancy (SPM) has become an increasingly important issue in these long-term survivors.

Methods

We conducted a retrospective study to analyze NHL patients diagnosed between January 1997 and December 2010 in Taiwan. Standardized incidence ratios (SIRs) were applied to compare the risk of SPMs in NHL patients and the general population. Multivariate analysis was performed to determine the independent predictors of SPM.

Result

NHL patients have a significantly greater risk of developing SPM [SIR 1.43; 95 % confidence interval (CI) 1.32–1.55; p < 0.001). A significantly high SIR was noted for leukemia, myeloma, and neoplasms of the bone and soft tissue, thyroid, central nervous system, skin, stomach, head and neck, liver and biliary tract, and the lungs and mediastinum. Multivariate analysis revealed that age ≥60 years [hazard ratios (HR) 2.04], being male (HR 1.22), comorbidities of chronic obstructive pulmonary disease (HR 1.34), liver cirrhosis (HR 1.50), hepatitis C infection (HR 1.94) and therapy containing radiotherapy (HR 1.38) were the significant predictors for SPM occurrence. The median follow-up time and survival time were 3.37 and 9.45 years, respectively.

Conclusion

This Taiwanese population-based study provides updated data about the risk of SPM in NHL patients, demonstrating an approximately 1.5 time greater risk of SPM compared to the general population. A high risk of SPM for myeloma and hepatocellular carcinoma is unique to Asian patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Bilimoria KY, Chung J, Ju MH, Haut ER, Bentrem DJ, Ko CY, Baker DW (2013) Evaluation of surveillance bias and the validity of the venous thromboembolism quality measure. JAMA 310(14):1482–1489

    Article  CAS  PubMed  Google Scholar 

  • Brennan P, Scelo G, Hemminki K, Mellemkjaer L, Tracey E, Andersen A, Brewster DH, Pukkala E, McBride ML, Kliewer EV, Tonita JM, Seow A, Pompe-Kirn V, Martos C, Jonasson JG, Colin D, Boffetta P (2005) Second primary cancers among 109,000 cases of non-Hodgkin’s lymphoma. Br J Cancer 93(1):159–166

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chen CH, Su WW, Yang SS, Chang TT, Cheng KS, Lin HH, Wu SS, Lee CM, Changchien CS, Chen CJ, Sheu JC, Chen DS, Lu SN (2006) Long-term trends and geographic variations in the survival of patients with hepatocellular carcinoma: analysis of 11,312 patients in Taiwan. J Gastroenterol Hepatol 21(10):1561–1566

    Article  PubMed  Google Scholar 

  • Chen WL, Tsai WC, Chao TY, Sheu LF, Chou JM, Kao WY, Chen YC, Ho CL (2010) The clinicopathological analysis of 303 cases with malignant lymphoma classified according to the World Health Organization classification system in a single institute of Taiwan. Ann Hematol 89(6):553–562

    Article  PubMed  Google Scholar 

  • Curtis RE, Freedman DM, Ron E, Ries LA, Hacker DG, Edwards BK, Tucker MA, Fraumeni Jr JF (1973) New malignancies among cancer survivors. SEER cancer registries 2000

  • Dalia S, Chavez J, Castillo JJ, Sokol L (2013) Hepatitis B infection increases the risk of non-Hodgkin lymphoma: a meta-analysis of observational studies. Leuk Res 37(9):1107–1115

    Article  PubMed  Google Scholar 

  • De Roos AJ, Martinez-Maza O, Jerome KR, Mirick DK, Kopecky KJ, Madeleine MM, Magpantay L, Edlefsen KL, Lacroix AZ (2013) Investigation of epstein-barr virus as a potential cause of B-cell non-Hodgkin lymphoma in a prospective cohort. Cancer Epidemiol Biomarkers Prev 22(10):1747–1755

    Article  PubMed Central  PubMed  Google Scholar 

  • Geyer SM, Morton LM, Habermann TM, Allmer C, Davis S, Cozen W, Severson RK, Lynch CF, Wang SS, Maurer MJ, Hartge P, Cerhan JR (2010) Smoking, alcohol use, obesity, and overall survival from non-Hodgkin lymphoma: a population-based study. Cancer 116(12):2993–3000

    Article  PubMed Central  PubMed  Google Scholar 

  • Greene MH, Wilson J (1985) Second cancer following lymphatic and hematopoietic cancers in Connecticut, 1935–82. Natl Cancer Inst Monogr 68:191–217

    CAS  PubMed  Google Scholar 

  • Gundling F, Seidl H, Schmidtler F, Loffler N, Strassen I, Wolf P, Pehl C, Schmidt T, Schepp W (2011) Nonhepatic cancer in liver cirrhosis: a retrospective study of prevalence, complication rate after specific oncological treatment, follow-up and prognostic predictors of outcome in 354 patients with cirrhosis. Anticancer Res 31(9):2931–2938

    PubMed  Google Scholar 

  • Guo SE, Huang TJ, Huang JC, Lin MS, Hong RM, Chang CH, Chen MY (2013) Alcohol, betel-nut and cigarette consumption are negatively associated with health promoting behaviors in Taiwan: a cross-sectional study. BMC Public Health 13:257

    Article  PubMed Central  PubMed  Google Scholar 

  • Hemminki K, Lenner P, Sundquist J, Bermejo JL (2008) Risk of subsequent solid tumors after non-Hodgkin’s lymphoma: effect of diagnostic age and time since diagnosis. J Clin Oncol 26(11):1850–1857

    Article  PubMed  Google Scholar 

  • Kashigar A, Habbous S, Eng L, Irish B, Bissada E, Irish J, Brown D, Gilbert R, Gullane P, Xu W, Huang SH, Witterick I, Freeman J, O’Sullivan B, Waldron J, Liu G, Goldstein D (2013) Social environment, secondary smoking exposure, and smoking cessation among head and neck cancer patients. Cancer 119(15):2701–2709

    Article  PubMed  Google Scholar 

  • Kornum JB, Svaerke C, Thomsen RW, Lange P, Sorensen HT (2012) Chronic obstructive pulmonary disease and cancer risk: a Danish nationwide cohort study. Respir Med 106(6):845–852

    Article  PubMed  Google Scholar 

  • Lishner M, Slingerland J, Barr J, Panzarella T, Degendorfer P, Sutcliffe S (1991) Second malignant neoplasms in patients with non Hodgkin’s lymphoma. Hematol Oncol 9(3):169–179

    Article  CAS  PubMed  Google Scholar 

  • McGrath M, Wong JYY, Michaud D, Hunter DJ, De Vivo I (2007) Telomere length, cigarette smoking, and bladder cancer risk in men and women. Cancer Epidemiol Biomarkers Prev 16(4):815–819

    Article  CAS  PubMed  Google Scholar 

  • Morton LM, Curtis RE, Linet MS, Bluhm EC, Tucker MA, Caporaso N, Ries LAG, Fraumeni JF (2010) Second malignancy risks after non-Hodgkin’s lymphoma and chronic lymphocytic leukemia: differences by lymphoma subtype. J Clin Oncol 28(33):4935–4944

    Article  PubMed Central  PubMed  Google Scholar 

  • Mudie NY, Swerdlow AJ, Higgins CD, Smith P, Qiao Z, Hancock BW, Hoskin PJ, Linch DC (2006) Risk of second malignancy after non-Hodgkin’s lymphoma: a British Cohort Study. J Clin Oncol 24(10):1568–1574

    Article  PubMed  Google Scholar 

  • Ollberding NJ, Evens AM, Aschebrook-Kilfoy B, Caces DB, Weisenburger DD, Smith SM, Chiu BC (2013) Pre-diagnosis cigarette smoking and overall survival in non-Hodgkin lymphoma. Br J Haematol 163(3):352–356

    Article  PubMed Central  PubMed  Google Scholar 

  • Pfreundschuh M, Kuhnt E, Trumper L, Osterborg A, Trneny M, Shepherd L, Gill DS, Walewski J, Pettengell R, Jaeger U, Zinzani PL, Shpilberg O, Kvaloy S, de Nully Brown P, Stahel R, Milpied N, Lopez-Guillermo A, Poeschel V, Grass S, Loeffler M, Murawski N (2011) 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 12(11):1013–1022

    Article  CAS  PubMed  Google Scholar 

  • Pirani M, Marcheselli R, Marcheselli L, Bari A, Federico M, Sacchi S (2011) Risk for second malignancies in non-Hodgkin’s lymphoma survivors: a meta-analysis. Ann Oncol 22(8):1845–1858

    Article  CAS  PubMed  Google Scholar 

  • Sacchi S, Marcheselli L, Bari A, Marcheselli R, Pozzi S, Gobbi PG, Angrilli F, Brugiatelli M, Musto P, Federico M (2008a) Second malignancies after treatment of diffuse large B-cell non-Hodgkin’s lymphoma: a GISL cohort study. Haematologica 93(9):1335–1342

    Article  PubMed  Google Scholar 

  • Sacchi S, Marcheselli L, Bari A, Marcheselli R, Pozzi S, Luminari S, Lombardo M, Buda G, Lazzaro A, Gobbi PG, Stelitano C, Morabito F, Quarta G, Brugiatelli M (2008b) Secondary malignancies after treatment for indolent non-Hodgkin’s lymphoma: a 16-year follow-up study. Haematologica 93(3):398–404

    Article  PubMed  Google Scholar 

  • Siegel R, Ma J, Zou Z, Jemal A (2014) Cancer statistics 2014. CA Cancer J Clin 64(1):9–29

    Article  PubMed  Google Scholar 

  • Sievert W, Altraif I, Razavi HA, Abdo A, Ahmed EA, Alomair A, Amarapurkar D, Chen CH, Dou X, El Khayat H, Elshazly M, Esmat G, Guan R, Han KH, Koike K, Largen A, McCaughan G, Mogawer S, Monis A, Nawaz A, Piratvisuth T, Sanai FM, Sharara AI, Sibbel S, Sood A, Suh DJ, Wallace C, Young K, Negro F (2011) A systematic review of hepatitis C virus epidemiology in Asia, Australia and Egypt. Liver Int 31(Suppl. 2):61–80

    Article  PubMed  Google Scholar 

  • Smith L, Brinton LA, Spitz MR, Lam TK, Park Y, Hollenbeck AR, Freedman ND, Gierach GL (2012) Body mass index and risk of lung cancer among never, former, and current smokers. J Natl Cancer Inst 104(10):778–789

    Article  PubMed Central  PubMed  Google Scholar 

  • Takenaka T, Konda C, Sakano T, Shimoyama M, Kitahara T, Minato K, Watanabe S (1985) Second primary malignancies in lymphoma patients. Jpn J Clin Oncol 15(2):443–449

    CAS  PubMed  Google Scholar 

  • Tanaka H, Tsukuma H, Teshima H, Ajiki W, Koyama Y, Kinoshita N, Masaoka T, Oshima A (1997) Second primary cancers following non-Hodgkin’s lymphoma in Japan: increased risk of hepatocellular carcinoma. Jpn J Cancer Res 88(6):537–542

    Article  CAS  PubMed  Google Scholar 

  • Travis LB, Curtis RE, Glimelius B, Holowaty EJ, Van Leeuwen FE, Lynch CF, Hagenbeek A, Stovall M, Banks PM, Adami J et al (1995) Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin’s lymphoma. J Natl Cancer Inst 87(7):524–530

    Article  CAS  PubMed  Google Scholar 

  • Tward JD, Wendland MM, Shrieve DC, Szabo A, Gaffney DK (2006) The risk of secondary malignancies over 30 years after the treatment of non-Hodgkin lymphoma. Cancer 107(1):108–115

    Article  PubMed  Google Scholar 

  • van Kruijsdijk RC, van der Graaf Y, Peeters PH, Visseren FL (2013) Cancer risk in patients with manifest vascular disease: effects of smoking, obesity, and metabolic syndrome. Cancer Epidemiol Biomarkers Prev 22(7):1267–1277

    Article  PubMed  Google Scholar 

  • Wu CY, Chen YJ, Ho HJ, Hsu YC, Kuo KN, Wu MS, Lin JT (2012) Association between nucleoside analogues and risk of hepatitis B virus-related hepatocellular carcinoma recurrence following liver resection. JAMA 308(18):1906–1914

    Article  CAS  PubMed  Google Scholar 

  • Xu Y, Wang H, Zhou S, Yu M, Wang X, Fu K, Qian Z, Zhang H, Qiu L, Liu X, Wang P (2013) Risk of second malignant neoplasms after cyclophosphamide-based chemotherapy with or without radiotherapy for non-Hodgkin lymphoma. Leuk Lymphoma 54(7):1396–1404

    Article  CAS  PubMed  Google Scholar 

  • Yang HI, Lu SN, Liaw YF, You SL, Sun CA, Wang LY, Hsiao CK, Chen PJ, Chen DS, Chen CJ (2002) Hepatitis B e antigen and the risk of hepatocellular carcinoma. N Engl J Med 347(3):168–174

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study is supported by a Grant from Taipei Veterans General Hospital (V104E10-001, V104B-023, and V104C-182), Taiwan Clinical Oncology Research Foundation, and partially supported by Chong Hin Loon Memorial Cancer and Biotherapy Research Cancer, National Yang-Ming University. The study is based in part on data from the National Health Insurance Research Database provided by the Bureau of National Health Insurance, Department of Health and managed by National Health Research Institutes. The interpretation and conclusions contained herein do not represent those of the Bureau of National Health Insurance, Department of Health or National Health Research Institutes. Miss Chiu-Mei Yeh contributed significantly to the calculations and interpretations of statistical analyses in this study.

Conflict of interest

The authors declare no conflict of interest.

Author information

Author notes

    Authors and Affiliations

    1. Division of Hematology and Oncology, Department of Medicine, Taipei Veterans General Hospital, No. 201 Shipai Road, Sec. 2, Taipei, 11217, Taiwan

      Sheng-Hsuan Chien, Chia-Jen Liu, Jyh-Pyng Gau & Cheng-Hwai Tzeng

    2. School of Medicine, National Yang-Ming University, Taipei, Taiwan

      Chia-Jen Liu, Ying-Chung Hong, Chung-Jen Teng, Yu-Wen Hu, Tzeon-Jye Chiou, Jyh-Pyng Gau & Cheng-Hwai Tzeng

    3. Institute of Public Health, National Yang-Ming University, Taipei, Taiwan

      Chia-Jen Liu & Chiu-Mei Yeh

    4. Division of Hematology and Oncology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

      Ying-Chung Hong

    5. Division of Oncology and Hematology, Department of Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan

      Chung-Jen Teng

    6. Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan

      Yu-Wen Hu

    7. Department of Hematology and Oncology, Show Chwan Memorial Hospital, Changhua, Taiwan

      Fan-Chen Ku

    8. Division of Transfusion Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

      Tzeon-Jye Chiou

    Authors
    1. Sheng-Hsuan Chien
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Chia-Jen Liu
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Ying-Chung Hong
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Chung-Jen Teng
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Yu-Wen Hu
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Fan-Chen Ku
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Chiu-Mei Yeh
      View author publications

      You can also search for this author in PubMed Google Scholar

    8. Tzeon-Jye Chiou
      View author publications

      You can also search for this author in PubMed Google Scholar

    9. Jyh-Pyng Gau
      View author publications

      You can also search for this author in PubMed Google Scholar

    10. Cheng-Hwai Tzeng
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Jyh-Pyng Gau.

    Additional information

    Sheng-Hsuan Chien and Chia-Jen Liu contribute equally to this work.

    Electronic supplementary material

    Below is the link to the electronic supplementary material.

    Supplementary material 1 (DOCX 29 kb)

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Chien, SH., Liu, CJ., Hong, YC. et al. Development of second primary malignancy in patients with non-Hodgkin lymphoma: a nationwide population-based study. J Cancer Res Clin Oncol 141, 1995–2004 (2015). https://doi.org/10.1007/s00432-015-1979-1

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s00432-015-1979-1

    Keywords

    Search

    Navigation