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Risk for malignancies of infectious etiology among adult survivors of specific non-Hodgkin lymphoma subtypes

Megan M. Herr, Sara J. Schonfeld, Graça M. Dores, Eric A. Engels, Margaret A. Tucker, Rochelle E. Curtis and Lindsay M. Morton

Data supplements

Article Figures & Data

Figures

  • Figure 1.

    Risk for developing second primary stomach cancer among adult 1-year DLBCL and MZL survivors by site of DLBCL or MZL, 2000 to 2014. SIRs and exact Poisson-based 95% CIs compared the number of observed cases with that expected in the general population (additional details provided in “Methods”). P values to test differences in the SIRs were computed using a likelihood ratio test derived from Poisson regression models stratified by age at first primary NHL, sex, and latency, with the log of the expected numbers of cases included as an offset. All statistical tests were 2 sided. Created using GraphPad Prism (version 7; La Jolla, CA).

Tables

  • Table 1.

    Characteristics of 1-y survivors by type of first primary NHL diagnosed from age 20 to 84 y, 17 SEER registry areas, 2000 to 2014

    CharacteristicCLL/SLL, % (n = 42 119)DLBCL, % (n = 41 416)FL, % (n = 29 508)MZL, % (n = 14 001)
    Age at first primary NHL, y
     <6029.546.447.840.1
     ≥6070.553.652.259.9
     Mean65.959.760.462.5
    Mean follow-up time, y4.54.65.24.8
    Sex
     Male60.554.949.945.4
     Female39.545.150.154.6
    Race
     White/unknown90.184.090.483.9
     African American7.47.74.78.1
     Other2.58.34.98.0
    Year of first primary NHL diagnosis
     2000-200434.033.234.630.5
     2005-200936.836.237.737.8
     2010-201429.330.627.731.7
    First course of NHL treatment
     CT and RT0.624.47.54.6
     CT, no known RT21.161.849.227.9
     RT, no known CT0.72.09.320.1
     No known CT or RT77.611.834.047.4
    Stage at first primary NHL*
     Early71.551.642.551.3
     Advanced28.543.150.232.8
     Unknown5.37.315.9
    Primary site (NHL)
     Nodal64.340.0
     Extranodal, gastric4.620.3
     Extranodal, nongastric31.039.7
    HIV/AIDS status at NHL diagnosis
     Reported HIV/AIDS0.13.60.50.7
     No known HIV/AIDS99.996.499.599.3
    • CT, chemotherapy; RT, radiotherapy.

    • * Early stage: Ann Arbor stages I and II for DLBCL, FL, and MZL and no known initial treatment of CLL; advanced stage: Ann Arbor stages III and IV for DLBCL, FL, and MZL and any initial treatment of CLL.

  • Table 2.

    Risk for developing second primary infection-related solid tumors among adult 1-y NHL survivors, 17 SEER registry areas, 2000 to 2014

    Second primary malignancy siteFirst primary NHL subtypePheterogeneity*
    CLL/SLLDLBCLFLMZL
    ObsSIR95% CIObsSIR95% CIObsSIR95% CIObsSIR95% CI
    Oropharynx/tonsil301.080.73-1.54221.040.65-1.58181.000.59-1.5870.960.39-1.98.99
    Stomach390.700.50-0.96621.511.16-1.94260.810.53-1.19442.782.02-3.74<.01
    Anus161.570.90-2.55313.712.52-5.2750.670.22-1.5682.361.02-4.64<.01
    Liver541.040.78-1.36761.851.46-2.31320.980.67-1.39301.981.34-2.83<.01
    Cervix uteri70.780.31-1.6190.890.41-1.6980.870.38-1.72<50.680.14-1.98.98
    • Obs, observed.

    • * P values to test differences in SIRs across NHL subtypes were computed using likelihood ratio test derived from Poisson regression models adjusted for age at first primary NHL, sex, and latency, with log of expected numbers of cases included as offset. Exact numbers of cases are not reported for categories with <5 observed cases to maintain patient confidentiality. All statistical tests were 2 sided.

    • SIRs and exact Poisson-based 95% CIs compared number of observed cases with that expected in general population (additional details provided in “Methods”).

    • Indicates 95% CI excludes 1.00, corresponding to 2-sided P < .05.

  • Table 3.

    Risk for developing second primary infection-related solid tumors among reported HIV/AIDS+ adult DLBCL survivors, SEER, 2000 to 2014

    Second primary malignancy siteHIV/AIDSNo known HIV/AIDS*
    ObsSIR95% CIObsSIR95% CI
    Oropharynx/tonsil<51.250.03-6.94211.030.64-1.58
    Stomach00NA621.541.18-1.98
    Anus1468.3437.36-115172.091.22-3.34
    Liver<52.450.51-7.16731.831.43-2.30
    Cervix uteri<57.840.20-43.6980.800.35-1.58
    • NA, not applicable.

    • * Includes HIV/AIDS status NA, reflecting individual SEER registry practices.

    • Indicates 95% CI excludes 1.00, corresponding to 2-sided P < .05.

  • Table 4.

    Risk for developing second primary stomach cancer by age, sex, latency, and stage among adult 1-y NHL survivors, 17 SEER registry areas, 2000 to 2014

    CharacteristicCLL/SLLDLBCLFLMZL
    ObsSIR*95% CI*ObsSIR*95% CI*ObsSIR*95% CI*ObsSIR*95% CI*
    Age at first primary NHL, y
     <60<50.430.12-1.11171.751.02-2.80<50.230.03-0.83133.832.04-6.56
     ≥60350.760.53-1.06451.441.05-1.93241.030.66-1.54312.501.70-3.54
     Pheterogeneity.26.51.01.22
    Sex
     Male300.740.50-1.05381.370.97-1.88160.770.44-1.25272.801.84-4.07
     Female90.620.28-1.17241.821.16-2.70100.900.43-1.65172.761.61-4.42
    Pheterogeneity.60.27.78.98
    Latency, y
     <5260.750.49-1.10351.420.99-1.98160.880.50-1.43252.621.70-3.87
     ≥5130.630.34-1.08271.651.09-2.41100.730.35-1.34193.031.82-4.73
    Pheterogeneity.73.64.90.78
    Stage of first primary NHL§
     Early300.740.50-1.06301.340.91-1.92130.880.47-1.51313.792.58-5.39
     Advanced90.600.27-1.14281.741.16-2.52110.750.38-1.35102.000.96-3.68
     Unknown00NA<51.580.43-4.05<50.780.09-2.80<51.130.23-3.31
     Pheterogeneity.60.32.78.07
    Initial NHL treatment
     CT and RT00NA141.380.76-2.32<51.510.41-3.8856.642.15-15.48
     CT, no known RT60.570.21-1.23371.531.07-2.10110.750.37-1.34133.141.67-5.37
     RT, no known CT00NA<53.220.66-9.41<50.900.19-2.6372.260.91-4.65
     No known CT or RT330.750.52-1.0581.420.61-2.8180.710.31-1.40192.431.46-3.79
    Pheterogeneity.73.68.64.30
    • * SIRs and exact Poisson-based 95% CIs compared number of observed cases with that expected in general population (additional details provided in “Methods”).

    • Indicates 95% CI excludes 1.00, corresponding to 2-sided P < .05.

    • P values to test differences in SIRs were computed using likelihood ratio test derived from Poisson regression models stratified by age at first primary NHL, sex, and latency, with log of expected numbers of cases included as offset. Exact numbers of cases are not reported for categories with <5 observed cases to maintain patient confidentiality. All statistical tests were 2 sided.

    • § Early stage: stages I and II for DLBCL, FL, and MZL and no known initial treatment of CLL; advanced stage: stages III and IV for DLBCL, FL, and MZL and any initial treatment of CLL.

  • Table 5.

    Risk for developing second primary liver cancer by age, sex, latency, and stage among adult 1-y NHL survivors, 17 SEER registry areas, 2000 to 2014

    CharacteristicCLL/SLLDLBCLFLMZL
    ObsSIR*95% CI*ObsSIR*95% CI*ObsSIR*95% CI*ObsSIR*95% CI*
    Age at first primary NHL, y
     <60120.780.40-1.36452.892.11-3.87130.960.51-1.64142.681.47-4.50
      ≥60421.150.83-1.55311.210.82-1.72191.000.60-1.56161.610.92-2.61
    Pheterogeneity.25<.01>.50.24
    Sex
     Male410.970.70-1.32621.961.50-2.51220.900.56-1.36252.321.50-3.43
     Female131.320.70-2.25141.480.81-2.49101.240.59-2.2851.140.37-2.65
    Pheterogeneity.46>.50.39.16
    Latency, y
     <5321.010.69-1.42532.231.67-2.92241.350.86-2.00171.921.12-3.07
     ≥5221.090.68-1.65231.320.84-1.9980.540.24-1.07132.061.10-3.53
    Pheterogeneity>.50<.01.02>.50
    Stage of first primary NHL§
     Early411.090.78-1.48371.661.17-2.29120.820.42-1.43121.550.80-2.71
     Advanced130.900.48-1.54332.011.38-2.82181.170.69-1.85112.271.13-4.06
     Unknown00NA62.460.90-5.35<50.790.10-2.8672.731.10-5.61
    Pheterogeneity>.50>.50.36.40
    Initial NHL treatment
     CT and RT00NA131.260.67-2.1672.531.02-5.21<52.600.32-9.40
     CT, no known RT111.060.53-1.90522.121.58-2.78181.170.69-1.8581.990.86-3.93
     RT, no known CT00NA<52.330.28-8.43<50.300.01-1.65<50.670.08-2.40
     No known CT or RT431.050.76-1.4191.670.76-3.1760.550.20-1.19182.441.45-3.86
    Pheterogeneity.72.36.02.22
    • * SIRs and exact Poisson-based 95% CIs compared number of observed cases with that expected in general population (additional details provided in “Methods”).

    • Indicates 95% CI excludes 1.00, corresponding to 2-sided P < .05.

    • P values to test differences in SIRs were computed using likelihood ratio test derived from Poisson regression models stratified by age at first primary NHL, sex, and latency, with log of expected numbers of cases included as offset. Exact numbers of cases are not reported for categories with <5 observed cases to maintain patient confidentiality. All statistical tests were 2 sided.

    • § Early stage: stages I and II for DLBCL, FL, and MZL and no known initial treatment of CLL; advanced stage: stages III and IV for DLBCL, FL, and MZL and any initial treatment of CLL.