Table 4 Literature review of large NLPHL studies

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