Cancer Medicine 2018; 7(4):1118--1126

Introduction {#cam41383-sec-0001}
============

Nodular lymphocyte‐predominant Hodgkin lymphoma (NLPHL) represents approximately 5% of all Hodgkin lymphoma and is recognized to have a more indolent course and potentially an improved prognosis when compared with classical Hodgkin lymphoma (cHL) [1](#cam41383-bib-0001){ref-type="ref"}. While advanced‐stage (stages III‐IV) NLPHL is treated with upfront chemotherapy, the current standard of care for (stages I‐II) NLPHL in the United States includes involved site radiation therapy, as the preferred or standard option, for all stage I and stage II patients [2](#cam41383-bib-0002){ref-type="ref"}. This standard of care for NLPHL is primarily based on retrospective analyses and subgroup analyses of prospective trials [2](#cam41383-bib-0002){ref-type="ref"}, [3](#cam41383-bib-0003){ref-type="ref"}, [4](#cam41383-bib-0004){ref-type="ref"}, [5](#cam41383-bib-0005){ref-type="ref"}, [6](#cam41383-bib-0006){ref-type="ref"}, [7](#cam41383-bib-0007){ref-type="ref"}, [8](#cam41383-bib-0008){ref-type="ref"}. In the case of early‐stage cHL, there has been a decline in the United States (US) in radiotherapy utilization that has been associated, in some studies, with inferior survival following diagnosis[9](#cam41383-bib-0009){ref-type="ref"}. This trend is largely related to large, prospective randomized trials supporting a chemotherapy alone treatment strategy, but these trials do not exist in the setting of NLPHL [2](#cam41383-bib-0002){ref-type="ref"}.

Previous retrospective series have shown similar outcomes in patients with early‐stage NLPHL treated with radiation therapy with or without chemotherapy with complete response rates of ≥98% and 10‐year recurrence‐free survival of 68--77% [5](#cam41383-bib-0005){ref-type="ref"}, [8](#cam41383-bib-0008){ref-type="ref"}. More recently, a Surveillance, Epidemiology, and End Results (SEER)‐based analysis has shown similar results, with a 10‐year disease‐specific survival of 93% [1](#cam41383-bib-0001){ref-type="ref"}. The same study showed a decrease in radiation therapy utilization from 1988 to 2010, despite an overall survival benefit associated with the use of radiation therapy on multivariable analysis (hazard ratio, HR = 0.64, *P *=* *0.03) [1](#cam41383-bib-0001){ref-type="ref"}. Of note, this study was limited in that it was unable to evaluate the utilization and impact of systemic therapy in this patient population, a topic of considerable interest since the advent of the anti‐CD20 antibody rituximab (initially FDA approved in 1997 for relapsed or refractory low‐grade CD20‐positive non‐Hodgkin\'s lymphoma), which has demonstrated efficacy as monotherapy in the treatment of NLPHL [1](#cam41383-bib-0001){ref-type="ref"}, [10](#cam41383-bib-0010){ref-type="ref"}, [11](#cam41383-bib-0011){ref-type="ref"}, [12](#cam41383-bib-0012){ref-type="ref"}, [13](#cam41383-bib-0013){ref-type="ref"}.

Our aim was to update and further evaluate the patterns of care of radiotherapy utilization in the treatment of NLPHL in the United States and to define the relationship between treatment modality (i.e., systematic therapy and radiation therapy) and overall survival (OS) following diagnosis.

Methods and Materials {#cam41383-sec-0002}
=====================

Data source and cohort selection {#cam41383-sec-0003}
--------------------------------

The National Cancer Database (NCDB) is a prospectively collected database led by the American College of Surgeons that collects patient‐level data on patients with cancer diagnoses from participating institutions across the United States and Puerto Rico [14](#cam41383-bib-0014){ref-type="ref"}. It is a joint project of the American Cancer Society and the Commission on Cancer of the American College of Surgeons, who execute a Business Associate Agreement that includes a data use agreement with each of its Commission on Cancer‐accredited hospitals. Established in 1989, the database is a nationwide facility‐based comprehensive clinical surveillance resource oncology dataset that accounts for roughly 70% of new cancer diagnoses in the United States annually [14](#cam41383-bib-0014){ref-type="ref"}. This study was approved by our institutional review board prior to initiation.

The NCDB was queried for patients with known stage I or II NLPHL diagnosed from 2004 to 2012. Figure [1](#cam41383-fig-0001){ref-type="fig"} depicts the cohort selection process. Patients with contraindications to radiotherapy, patients who refused radiotherapy, and patients with unknown radiotherapy utilization were excluded, as were patients with unknown OS following diagnosis (lost to follow‐up). Patient age, year of diagnosis, sex, race, median income of patient ZIP code, distance from patient home to hospital, Charlson/Deyo comorbidity score, insurance status, stage, and the presence/absence of B‐symptoms were extracted from the NCDB dataset for analysis [15](#cam41383-bib-0015){ref-type="ref"}. For interpretation and analysis, patients were then categorized into one of four therapy groups based on treatment modality: radiation alone, chemotherapy alone, chemoradiotherapy, and neither.

![Cohort selection diagram.](CAM4-7-1118-g001){#cam41383-fig-0001}

Statistical analyses {#cam41383-sec-0004}
--------------------

Chi‐squared tests of independence were performed to compare each categorical demographic and clinical covariate between the four therapy groups. The primary outcome measure of this study was overall survival (OS) following diagnosis of NLPHL based on treatment strategy. Time to death or last follow‐up was evaluated using the log‐rank test as well as an unadjusted and multivariable Cox proportional hazards models including propensity score (PS) inverse probability of treatment weighting (IPTW). All statistical analyses were performed using R version 3.1 (The R Foundation for Statistical Computing, Auckland, New Zealand). The "twang" package in R was used to estimate the propensity scores for each treatment group. We further confirmed that each patient has a nonzero probability of receiving each treatment and that all the covariates were balanced across the four therapy arms. As missing data were infrequent in the included covariates (\<5% within each therapy group), indicators for missingness were used in the models. This approach has been shown to be appropriate when using propensity score adjustment [16](#cam41383-bib-0016){ref-type="ref"}, [17](#cam41383-bib-0017){ref-type="ref"}. Results were considered statistically significant with *P *\<* *0.05.

Results {#cam41383-sec-0005}
=======

Clinical characteristics {#cam41383-sec-0006}
------------------------

After planned exclusions, 1420 patients with early‐stage NLPHL with known therapy and survival information were identified from the NCDB database (Fig. [1](#cam41383-fig-0001){ref-type="fig"}). As demonstrated, 571 (40%) patients received radiation therapy alone, 318 (22%) received chemotherapy alone, 351 (25%) received both, and 180 (13%) received neither chemotherapy nor radiation therapy as part of their initial treatment course.

Table [1](#cam41383-tbl-0001){ref-type="table-wrap"} describes the patient characteristics of the patient cohort grouped by therapy, with a chi‐squared test to evaluate the difference across groups. The median age among patients was 45 years among patients treated with radiation therapy and 48 years among those in whom radiation therapy was omitted. Both groups were male predominant. Most patients identified themselves as white (69%) or black (22%) in both groups. Of evaluated patients, 58% of identified patients were stage I, the remainder stage II (42%), and clinical stage at presentation predicted for the use of a chemotherapy‐containing approach (*P *\<* *0.001).

###### 

Clinical characteristics of the 1420 patients with early‐stage nodular lymphocyte‐predominant Hodgkin lymphoma in the National Cancer Database 2004--2012

  Test                                                          No treatment   Radiation only   Chemo only   Both   Chi‐square                   
  ------------------------------------------------------------- -------------- ---------------- ------------ ------ ------------ ---- ----- ---- ------------------------------------------------
  Total number                                                  180            13               571          40     318          22   351   25   
  Age                                                                                                                                            
  ≤60                                                           133            74               448          78     239          75   308   88   \<0.001
  \>60                                                          47             26               123          22     79           25   43    12   
  Year of Diagnosis (median)                                                                                                                     
  2004                                                          14             8                35           6      23           7    38    11   0.052
  2005                                                          18             10               34           6      26           8    43    12   
  2006                                                          10             6                37           6      23           7    32    9    
  2007                                                          17             9                46           8      28           9    38    11   
  2008                                                          20             11               76           13     35           11   36    10   
  2009                                                          22             12               72           13     42           13   41    12   
  2010                                                          24             13               76           13     43           14   46    13   
  2011                                                          31             17               95           17     49           15   38    11   
  2012                                                          24             13               100          18     49           15   39    11   
  Sex                                                                                                                                            
  Male                                                          99             55               372          65     201          63   250   71   0.002
  Female                                                        81             45               199          35     117          37   101   29   
  Race                                                                                                                                           
  White                                                         102            57               385          67     227          71   259   74   \<0.001[a](#cam41383-note-0002){ref-type="fn"}
  Black                                                         59             33               122          21     70           22   65    19   
  American Indian                                               0              0                3            1      0            0    2     1    
  Asian/Pacific Islander                                        0              0                11           2      5            2    2     1    
  Hispanic                                                      16             9                43           8      12           4    21    6    
  Unknown                                                       0              0                7            1      4            1    2     1    
  Median income of zip[b](#cam41383-note-0003){ref-type="fn"}                                                                                    
  \<\$38,000                                                    49             27               94           16     51           16   51    15   0.021
  \$38,000--\$47,999                                            27             15               125          22     64           20   85    24   
  \$48,000--\$62,999                                            42             23               151          26     84           26   98    28   
  \$63,000+                                                     58             32               196          34     111          35   108   31   
  Unknown                                                       4              2                6            1      8            3    9     3    
  Distance to Hospital[b](#cam41383-note-0003){ref-type="fn"}                                                0                                   
  \<25 min                                                      146            81               469          82     259          81   267   76   0.269
  25--100 min                                                   25             14               75           13     38           12   64    18   
  \>100 min                                                     5              3                21           4      14           4    12    3    
  Unknown                                                       4              2                6            1      7            2    8     2    
  Charlson/Deyo Score                                                                                                                            
  0                                                             152            84               503          88     275          86   322   92   0.117
  1                                                             25             14               55           10     35           11   21    6    
  2                                                             3              2                13           2      8            3    8     2    
  Insurance                                                                                                                                      
  No                                                            7              4                25           4      16           5    17    5    0.929
  Yes                                                           173            96               546          96     302          95   334   95   
  Stage                                                                                                                                          
  Stage I                                                       130            72               412          72     126          40   161   46   \<0.001
  Stage II                                                      50             28               159          28     192          60   190   54   
  B‐symptoms[b](#cam41383-note-0003){ref-type="fn"}                                                                                              
  No                                                            73             41               418          73     143          45   204   58   \<0.001
  Yes                                                           6              3                14           2      36           11   32    9    
  Unknown                                                       101            56               139          24     139          44   115   33   

Compares only White, Black, and Hispanic groups because of small samples of other subgroups.

For variables with a significant amount of unknown data points (income, distance, and B‐symptoms), the unknown category was removed in the comparison.

John Wiley & Sons, Ltd

Factors associated with radiation therapy {#cam41383-sec-0007}
-----------------------------------------

Table [2](#cam41383-tbl-0002){ref-type="table-wrap"} depicts the analysis of factors associated with receipt of radiation therapy. Because of the large percentage of patients with unknown B‐symptoms, this was not included in the utilization model. As demonstrated, factors associated with decreased odds of receiving radiotherapy included younger age (*P *=* *0.001), female sex (*P *=* *0.019), and the use of chemotherapy (*P *\<* *0.001) on multivariable analysis. While median household income and Charlson/Deyo score appear to be associated with radiotherapy utilization, a clear trend did not emerge. Of note, stage II NLPHL was not associated with a change in radiotherapy utilization compared to stage I (*P *=* *0.170). Figure [2](#cam41383-fig-0002){ref-type="fig"} demonstrates the relatively stable trend in therapy utilization over the study period (*P *=* *0.640).

###### 

Analysis of factors associated with the receipt of radiotherapy for early‐stage nodular lymphocyte‐predominant Hodgkin lymphoma in the National Cancer Database 2004--2012

                                                             Univariable   Multivariable                  
  ---------------------------------------------------------- ------------- --------------- -------------- ---------
  Patient age[a](#cam41383-note-0004){ref-type="fn"}         \<0.001       0.987           0.980--0.995   0.001
  Year of diagnosis[a](#cam41383-note-0004){ref-type="fn"}   0.640                                        
  Sex                                                        0.007                                        0.019
  Male                                                                     ref                            
  Female                                                                   0.745           0.583--0.952   
  Race                                                       0.219                                        
  Median income of zip                                       0.069                                        0.022
  \<\$38,000                                                               ref                            
  \$38,000--\$47,999                                                       1.764           1.216--2.557   0.003
  \$48,000--\$62,999                                                       1.487           1.048--2.110   0.026
  \$63,000+                                                                1.313           0.941--1.832   0.109
  Distance to Hospital                                       0.505                                        
  Charlson/Deyo Score                                        0.069                                        0.170
  0                                                                        ref                            
  1                                                                        0.703           0.479--1.030   0.071
  2                                                                        1.168           0.535--2.551   0.696
  Insurance                                                  0.957                                        
  No                                                                                                      
  Yes                                                                                                     
  Stage                                                      \<0.001                                      0.170
  Stage I                                                                  ref                            
  Stage II                                                                 0.844           0.663--1.075   
  Chemotherapy                                               \<0.001                                      \<0.001
  No                                                                       ref                            
  Yes                                                                      0.325           0.254--0.415   

Analyzed as a continuous variable.

OR, odds ratio of receiving radiotherapy; CI, confidence interval.

John Wiley & Sons, Ltd

![Utilization of therapies over time for patients with early‐stage nodular lymphocyte‐predominant Hodgkin lymphoma in the National Cancer Database (2004--2012).](CAM4-7-1118-g002){#cam41383-fig-0002}

Overall survival analyses {#cam41383-sec-0008}
-------------------------

Median follow‐up among the entire cohort was 48.3 months following diagnosis. Figure [3](#cam41383-fig-0003){ref-type="fig"} provides the unadjusted Kaplan--Meier product limit estimates and PS‐weighted survival curves of OS following diagnosis based on therapy received (*P *\<* *0.001). The 10‐year unadjusted OS estimate for the no therapy, radiotherapy, chemotherapy, and chemoradiotherapy groups was 87%, 93%, 80%, and 92%, respectively. Table [3](#cam41383-tbl-0003){ref-type="table-wrap"} provides the detailed analysis of factors associated with survival among the study cohort. As demonstrated, older age (HR = 4.082 for age \>60 years, *P *\<* *0.001), Charlson/Deyo score, and omission of initial therapy were associated with shortened time to death on multivariable analysis.

![Overall survival following diagnosis among 1420 patients with early‐stage nodular lymphocyte‐predominant Hodgkin lymphoma in the National Cancer Database (2004--2012, shading represents 95% confidence interval).](CAM4-7-1118-g003){#cam41383-fig-0003}

###### 

Analysis of factors associated with time to death among patients with early‐stage nodular‐lymphocyte predominant Hodgkin lymphoma in the National Cancer Database 2004--2012

                           Unadjusted Cox model   Multivariable Cox model   Propensity Score weighted                                                            
  ------------------------ ---------------------- ------------------------- --------------------------- ------- --------------- --------- ------- -------------- ---------
  Therapy                                                                                                                                                        
  None                     1.000                  --                        --                          1.000   --              --        1.000   --             --
  Radiation                0.302                  0.156--0.586              \<0.001                     0.294   0.148--0.583    \<0.001   0.298   0.211--0.423   \<0.001
  Chemotherapy             1.023                  0.571--1.833              0.939                       0.849   0.456--1.582    0.607     0.784   0.598--1.028   0.078
  Both                     0.271                  0.129--0.568              \<0.001                     0.287   0.131--0.627    0.002     0.258   0.179--0.373   \<0.001
  Patient age                                                                                                                                                    
  ≤60                                                                                                   1.000   --              --                               
  \>60                                                                                                  4.082   2.521--6.61     \<0.001                          
  Year of Diagnosis                                                                                                                                              
  2004                                                                                                  1.000   --              --                               
  2005                                                                                                  1.551   0.647--3.722    0.325                            
  2006                                                                                                  1.253   0.467--3.36     0.654                            
  2007                                                                                                  0.391   0.103--1.486    0.168                            
  2008                                                                                                  1.424   0.548--3.699    0.468                            
  2009                                                                                                  1.283   0.503--3.278    0.602                            
  2010                                                                                                  1.596   0.590--4.318    0.357                            
  2011                                                                                                  1.547   0.541--4.424    0.415                            
  2012                                                                                                  1.143   0.346--3.774    0.827                            
  Sex                                                                                                                                                            
  Male                                                                                                  1.000   --              --                               
  Female                                                                                                0.635   0.393--1.028    0.065                            
  Race                                                                                                                                                           
  White                                                                                                 1.000   --              --                               
  Black                                                                                                 1.254   0.703--2.238    0.443                            
  American Indian                                                                                       7.464   0.937--59.436   0.058                            
  Asian/Pacific Islander                                                                                0.000   NA              0.996                            
  Unknown                                                                                               0.750   0.214--2.63     0.653                            
  Hispanic                                                                                              0.000   NA              0.997                            
  Median income of zip                                                                                                                                           
  \<\$38,000                                                                                            1.000   --              --                               
  \$38,000--\$47,999                                                                                    0.000   NA              0.999                            
  \$48,000--\$62,999                                                                                    1.265   0.631--2.538    0.508                            
  \$63,000+                                                                                             0.714   0.339--1.505    0.376                            
  Unknown                                                                                               0.601   0.290--1.243    0.170                            
  Distance to Hospital                                                                                                                                           
  \<25 min                                                                                              1.000   --              --                               
  25--100 min                                                                                           1.001   0.515--1.947    0.997                            
  \>100 min                                                                                             0.898   0.210--3.832    0.884                            
  Unknown                                                                                               NA      NA              0.999                            
  Charlson/Deyo Score                                                                                                                                            
  0                                                                                                     1.000   --              --                               
  1                                                                                                     1.760   0.971--3.189    0.062                            
  2                                                                                                     3.508   1.417--8.682    0.007                            
  Insurance                                                                                                                                                      
  No                                                                                                    1.000   --              --                               
  Yes                                                                                                   0.809   0.235--2.779    0.736                            
  Stage                                                                                                                                                          
  Stage I                                                                                               1.000   --              --                               
  Stage II                                                                                              1.539   0.955--2.479    0.077                            

HR, hazard ratio of death; CI, confidence interval; mi, miles.

John Wiley & Sons, Ltd

In comparing outcomes based on treatment modality on multivariable PS‐weighted analysis, radiation therapy alone and chemoradiotherapy were associated with improved survival as compared to no treatment (HR = 0.298 and 0.258, respectively, both *P *\<* *0.001). In contrast, the use of chemotherapy alone suggested, but failed to confirm, an improvement in OS compared to no treatment (HR = 0.784, *P *=* *0.078). Additional, similar analyses confirmed these findings through independent groupings of therapy (radiotherapy vs. no radiotherapy, radiotherapy vs. chemotherapy, and radiotherapy vs. chemoradiotherapy, and chemotherapy alone vs. chemoradiotherapy). These results are provided in the supplementary materials (Figs [\[Link\]](#cam41383-sup-0001){ref-type="supplementary-material"}, [\[Link\]](#cam41383-sup-0002){ref-type="supplementary-material"}, [\[Link\]](#cam41383-sup-0003){ref-type="supplementary-material"}, [\[Link\]](#cam41383-sup-0004){ref-type="supplementary-material"} and Tables [S1--S3](#cam41383-sup-0005){ref-type="supplementary-material"}).

Discussion {#cam41383-sec-0009}
==========

In the largest series on NLPHL to date, our findings are consistent with prior studies which have shown an excellent OS after treatment of NLPHL, with 10‐year OS between 90% and 100% [1](#cam41383-bib-0001){ref-type="ref"}, [5](#cam41383-bib-0005){ref-type="ref"}, [8](#cam41383-bib-0008){ref-type="ref"}. Our findings are also consistent with prior database studies showing an improvement in OS associated with the receipt of radiation therapy [1](#cam41383-bib-0001){ref-type="ref"}, [18](#cam41383-bib-0018){ref-type="ref"}. In a similar recent study, Odei et al. utilized the NCDB to evaluate factors associated with survival among patients will all stages of NLPHL [18](#cam41383-bib-0018){ref-type="ref"}. Their results independently affirm our findings, favoring radiotherapy utilization, in patients with early stage, and also in patients with advanced‐stage NLPHL [18](#cam41383-bib-0018){ref-type="ref"}. Given the improvement in OS associated with radiation therapy and chemoradiation seen in these studies, and not in nonradiotherapy containing approaches, there is support of the current National Comprehensive Cancer Network (NCCN) Guidelines recommendation for the use of radiation therapy, possibly in conjunction with chemotherapy, for patients with early‐stage NLPHL [2](#cam41383-bib-0002){ref-type="ref"}.

Per the NCCN guidelines, either involved site radiation therapy (preferred) or careful observation (in highly selected patients) is appropriate treatment options for stages IA and IIA NLPHL with combined modality therapy (chemoradiotherapy) for patients with early‐stage bulky disease and patients with B‐symptoms [2](#cam41383-bib-0002){ref-type="ref"}. The NCCN does not support the use of chemotherapy alone in patients with early‐stage NLPHL. Despite this consensus recommendation, 22% of patients in our study were treated with chemotherapy alone.

The cause of these variations in practice patterns is complex [9](#cam41383-bib-0009){ref-type="ref"}, but we suspect are related to referral patterns to medical oncologists but not radiation oncologists, lack of recognition of the benefit of radiotherapy in the treatment of NLPHL, and the practice of treating NLPHL patients in the same manner as cHL patients. The lowered utilization of radiotherapy among younger, female patients suggests that the possible late effects of radiotherapy (including cardiovascular disease and secondary malignancies such as breast cancer) are a driver in decision‐making in favor of systemic therapy alone approaches. While it does appear that the recent decline in radiotherapy utilization for NLPHL patients identified in previous studies has stabilized [1](#cam41383-bib-0001){ref-type="ref"}, our analysis shows that more than 25% of patients receiving treatment for early‐stage NLPHL did not receive radiation therapy.

In the era of rituximab, multiple series have demonstrated that focal radiotherapy is associated with improved disease control compared to systemic therapy [12](#cam41383-bib-0012){ref-type="ref"}, [19](#cam41383-bib-0019){ref-type="ref"}. Perhaps related to sample size or uncontrolled confounders, these studies failed to demonstrate a difference in OS between upfront systemic therapy and radiotherapy. In contrast, in the current series, we found that patients treated with chemotherapy alone or with observation had inferior OS compared to those treated with radiotherapy (Fig. [3](#cam41383-fig-0003){ref-type="fig"}). An important caveat is that during the study period (2004--2012), the NCDB did not code for cytotoxic chemotherapy and targeted therapies differently. Beginning in 2013, rituximab is now to be classified as an immunotherapeutic agent, not a chemotherapy [15](#cam41383-bib-0015){ref-type="ref"}. As a result, we suspect that the chemotherapy utilized in the patients in this series consists of those treated with both cytotoxic agents and targeted agents.

The primary limitation of our study is the potential for confounding in a retrospective analysis. It is possible that some uncontrolled variable (B‐symptoms, bulky disease, and interim metabolic imaging such as PET‐CT scans, radiotherapy technique, dose, fractionation, among others) could influence both treatment utilization and survival in this cohort, including treatment bias. However, using propensity score weighting, we adjusted for all confounders that we had available and think have an important effect on treatment decisions and survival. If healthier patients were treated with radiation therapy in ways which were not controlled for in this study, we would overestimate the benefit of radiation therapy.

Of note, the NCDB records the first round of treatment at diagnosis. Therefore, the salvage strategies among this cohort are unknown. However, the OS difference demonstrated here likely includes patients treated with salvage radiotherapy as well as salvage stem cell transplant, raising concern over the potential efficacy of such a salvage strategy on patient survival. Similarly, while OS is reported herein, other critical considerations such as relapse‐free survival, treatment‐induced toxicity, and cause of death are not reported in the NCDB and will be of value in future studies.

This large database analysis shows an improvement in OS associated with the use of radiation therapy in early‐stage NLPHL. Despite this benefit, 35% of patients with early‐stage NLPHL do not receive radiation therapy at diagnosis. Given the rarity of this histologic subtype, we believe that it is unlikely that randomized trials will be conducted in this setting. As a result, we believe that large database analyses, such as the current one, can serve an important role in identifying disparities in care and improving patient outcomes.

Conflict of Interest {#cam41383-sec-0010}
====================

The authors declare no disclaimers or conflict of interests.

Supporting information
======================

###### 

**Figure S1.** Overall survival following diagnosis among patients with early stage nodular lymphocyte predominant Hodgkin lymphoma in the National Cancer Database (2004--2012) comparing radiotherapy use to none.

###### 

Click here for additional data file.

###### 

**Figure S2.** Overall survival following diagnosis among patients with early stage nodular lymphocyte predominant Hodgkin lymphoma in the National Cancer Database (2004--2012) comparing radiotherapy use to chemotherapy use.

###### 

Click here for additional data file.

###### 

**Figure S3.** Overall survival following diagnosis among patients with early stage nodular lymphocyte predominant Hodgkin lymphoma in the National Cancer Database (2004--2012) comparing radiotherapy use to chemoradiotherapy use.

###### 

Click here for additional data file.

###### 

**Figure S4.** Overall survival following diagnosis among patients with early stage nodular lymphocyte predominant Hodgkin lymphoma in the National Cancer Database (2004--2012) comparing chemotherapy use to chemoradiotherapy use.

###### 

Click here for additional data file.

###### 

**Table S1.** Analysis of factors associated with time to death among patients with early stage nodular lymphocyte predominant Hodgkin lymphoma in the National Cancer Database 2004--2012 comparing radiotherapy use to none.

**Table S2.** Analysis of factors associated with time to death among patients with early stage nodular lymphocyte predominant Hodgkin lymphoma in the National Cancer Database 2004--2012 comparing radiotherapy use to chemotherapy use.

**Table S3.** Analysis of factors associated with time to death among patients with early stage nodular lymphocyte predominant Hodgkin lymphoma in the National Cancer Database 2004--2012 comparing radiotherapy use to chemoradiotherapy use.

###### 

Click here for additional data file.
