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Table 4 Literature review of large NLPHL studies

From: Nodular lymphocyte-predominant Hodgkin lymphoma characteristics, management of primary and relapsed/refractory disease and outcome analysis: the first comprehensive report from the Middle East

Study (Publication year) Study Design (years of treatment) Numbers Stage / population Modality of Treatment Median Follow up PFS / EFS OS Rx for failure or 2nd line Rx Median age (range) Comments
Diehl et al. 1999 [20] Retrospective 1980s 219 Stage I-IV All 6.8 NA (8 years)   No 35 (16-NA) 17 international centers. Treated in 1980s. MOPP based therapy. Compared NLPHL vs lymphocyte rich variant.
   I    85% 99    
   II    71% 94    
   III    62% 94    
   IV    24% 41    
Wirth et al. (2005) [21] Retrospective 1969–1995 202 Stage I–II RT 15 82% (15 years) 83% (15 years) Yes 31 (2–79) Australian. Age > 45 years, B symptoms, and number of involved sites with inferior OS.
Nogova´ et al. (2008) [18] Retrospective 394 Stage I-IV All 50 m 88% 96% No 37 (16–75) GHSG HD12 and HD14. Inferior PFS with advanced stage, low Hb and lymphopenia. Study to compare NLPHL vs cHL, showed better outcome for NLPHL than cHL
    early Favor    93%     
   early unfav    87%     
   advanced    77%     
Chen et al. (2010) [22] Retrospective 70–2005 113 Stage I–II RT, CMT, CT 136 at 10 years at 10 years Yes 27 (3–77) From Boston, USA. RT 82% pts., CMT 12% and CT alone 6%. PFS limited RT 64%, regional RT 84%, EFRT 81%. Chemo + RT with inferior OS.
    Stage I    85% 96%    
   Stage II    61% 100%    
Biasoli et al. (2010) [3] Retrospective (1973–2003) 164 Stage I-IV   9.5 yrs 60% (10 yrs) 91% (10 yrs) Yes 30 (6–69) French centers, 158 stage I-II. 11.6% had transformation
    any Rx   66% 93%    
    No Rx   41% 91%    
Solanki et al. 2013 [23] Retrospective 1988–2009 469 Stage I-II NA 6 yrs NA 88% No 37 [4–88] SEER data USA. older age, female gender, multiple nodal regions and B-symptoms with inferior OS.
Eichenauer et al. (2015) [24] Retrospective 1988–2009 256 Stage IA   91 m 88.9% (8 years) 98.2 (8 years) No 39 (16–75) GHSG 1988–2009 studies. All have similar tumor control. IFRT with less toxicity.
  72   CMT 95 88.5% (8 years) 98.6% (8 years)    
  49   EFRT 110 84.3% (8 years) 95.7% (8 years)    
  108   IFRT 87 91.9% (8 years) 99.0% (8 years)    
  27   Rituximab 49 81% (4 years) 100% (4 years)    
Gerber et al. 2015 [25] Retrospective 1988–2010 1162 Stage I-IV NA 7 yrs NA 91% & 83% (5–10 yrs) No 38 (not available) SEER data USA. A Population-Based analysis on NLPHL vs cHL. No info related to chemo.
Lazarovici et al. (2015) [5] Retrospective (1974–2012) 314 Stage I-IV All 55.8 m 44.2% (10 yrs) 94.9% (10 yrs) Yes 38 (18–79) LYSA (France + Belgium). 82.5 stages I-II. Transformation 7.6%
    CT   78.8% (4 yrs)     
    RT   79.6% (4 yrs)     
    CMT   93.9% (4 yrs)     
Parikh et al. 2016 [26] Retrospective 1998–2011 1016 Stage I-II   6.6 yrs NA   No 44 (18–90) National Data Base (USA). Exploring the impact of RT, showed that RT use with better OS.
    No RT    88.10%    
    Yes RT    94.10%    
Kenderian et al. 2016 [8] Retrospective 1970–2011 222 Stage I-IV   16.3 yrs NA   No 40 (15–81) Mayo Clinic. Focused on HGT, 8.1% HGT at a median of 35 months, 76% 5 yr OS. No difference in OS of HGT vs no HGT NLPHL pts.
    HGT     76.4 (5 yrs)    
    No HGT     similar as transformed    
Molin et al. (2017) [27] Retrospective (2000–2014) 158 Stage I-IV All 7.3 yrs NA 94 and 79% (5-10 yrs) No 48 (16–88) male 44 female 59 Swedish Cancer Registry. No survival benefit of RT vs CMT in stages I-IIA. Rituximab with chemo superior to chemo alone in IIB-IV patients.
    Stages I-IIA     98 and 85%    
   stages IIB-IV     87 and 67%    
Shivarov 2018 [28] Retrospective (2000–2014) 1401 Stage I-IV   NA NA    43 (16–92) male 41 female 48 SEER data USA. OS extracted from the figure. Older age, stage III-IV and not using RT with inferior OS. Female older at Dx.
   I-II     90 approx    
   III-IV     75 approx    
Alonso et al. (2018) [29] Retrospective (2004–2012) 1420 Stage I-II   48.3 m NA (10 years) No 45 RT gp, 48 No RT gp National Data Base (USA). Age > 60 and not using RT with inferior OS.
    No Rx    87%   48  
    CT    80%   48  
    RT    93%   45  
    CMT    92%   45  
Posthuma et al. (2019) [19] Retrospective (1993–2016) 687 Stage I-IV All 7.7 yrs NA (5–10 yrs) No 4–87 Netherland Cancer Registry. Increase in median age over time. No excess mortality compared to general population in pts. age 18–39.
   Stage I-II No Rx    93–80%   42 (2003–2016)  
    RT    99–99%    
    Chemo +/− RT    90–89%    
   stage III-IV No Rx    61–57%    
    Chemo +/− RT    89–80%    
Borchmann et al. (2019) [4] Retrospective (1974–2016) 163 Stage I-IV All 69 m 85% (5 yrs) 99% (5 yrs)   40 (16–75) Memorial Sloan Kettering USA, transformation 7.4% at 7 years median. Shorter PFS with extranodal and bulky disease > 5 cm. Non RT Rx with inferior PFS
    No Rx   77% 100% Yes   
    any Rx   87% 98%    
   Early stage No Rx   65%     
    any Rx   94%     
    With RT   94%     
    without RT   73%     
Eichenauer et al 2019 [6] Retrospective 471 Stage I-IV   9.2 yrs 75.5% 92.10%   39 (16–75) GHSG HD7 to HD15. HGT 2.54%. 23% of all deaths due to NLPHL
   early Favor    79.7% 93.30%    
   early unfav    72.1% 96.20%    
   advanced    69.8% 87.40%    
Wilson et al. 2019 [7] Retrospective (2004–2014) 233 Stage I-IV All 8.6 88% (estimated) 97% (5 yrs) No 43 (< 16 only 5%) Multi-institution from UK. HGT 6%.
    No Rx    96.70%    
    RT    98.3    
    RT +/− chemo    95.2    
Current study Retrospective 1998–2019 200 Stage I-IV All 5 62.3% & 54% [5,6,7,8,9,10] 94.8% & 92.4 (5–10) Yes 22 (4–79) Single institution. Chemo + RT with better EFS than chemo alone. High incidence of familial malignancies, large numbers with HDC auto-SCT,
   I    72% (10 yrs) 97.7    
   II    55.7% 97.7    
   III    20% 87.6    
   IV    26.8% 79.5    
  1. Abbreviations: Same as Tables 1 and 2, PFS Progression free survival, EFS Event free survival, Rx Treatment, GHSG German Hodgkin Lymphoma Study Group, SEER Surveillance, Epidemiology, and End Results, CMT Combined modality treatment, EFRT Extended field RT, IFRT Involved field RT, HGT High grade transformation