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Favorable outcomes with de-escalated radiation therapy for limited-stage nodular lymphocyte-predominant Hodgkin lymphoma

Chelsea C. Pinnix, Sarah A. Milgrom, Chan Yoon Cheah, Jillian R. Gunther, Ethan B. Ludmir, Christine F. Wogan, Loretta J. Nastoupil, Sattva S. Neelapu, Jason Westin, Hun J. Lee, Swaminathan P. Iyer, Raphael E. Steiner, Luis E. Fayad, Nathan H. Fowler, Michael L. Wang, Felipe Samaniego, Maria A. Rodriguez, Amy E. Rich, L. Jeffrey Medeiros and Bouthaina S. Dabaja

Article Figures & Data

Figures

  • Figure 1.

    Treatment of stage IA NLPHL of the right neck with IFRT vs ISRT. Diagnostic PET-CT scout (A), coronal (B), and axial (D) images of a patient with fluorodeoxyglucose-avid stage IA NLPHL of the right neck treated with IFRT. Coronal (C) and axial (E) CT images from the 3-dimensional radiation treatment plan illustrate the gross disease (contoured in red) and the extended clinical treatment volume (contoured in yellow). Diagnostic PET-CT scout (F), coronal (G), and axial (I) images of a second patient with stage IA NLPHL of the right neck treated with ISRT. Coronal (H) and axial (J) images from the RT plan illustrate the gross tumor volume (contoured in red) and the more limited clinical tumor volume (contoured in yellow).

  • Figure 2.

    Outcomes for all patients with limited-stage NLPHL. PFS (A), OS (B), LDFS (C), and DDFS (D) among all 71 patients with stage I or stage II NLPHL treated from 1987 through 2017. Dotted lines indicate 95% CIs.

  • Figure 3.

    Outcomes according to treatment of patients with limited-stage NLPHL. PFS (A), OS (B), LDFS (C), and DDFS (D) for patients with stage I/II NLPHL treated with RT only (n = 36), CMT (n = 29), or systemic therapy (ST) only (n = 6).

  • Figure 4.

    Outcomes among patients treated with RT or CMT according to radiation field size. PFS (A,D), LDFS (B,E), and DDFS (C,F) among patients treated with RT only or CMT according to field size.

Tables

  • Table 1.

    Patient and disease characteristics

    CharacteristicAll patients (N = 71)RT only (n = 36)Combined therapy (n = 29)RT-only vs combined therapy, PSystemic therapy only (n = 6)
    Age
     Median (range), y39 (18-73)38 (18-69)40 (22-73)49 (31-68)
     ≥45 y30 (42)15 (42)11 (38).8034 (67)
    Male53 (75)26 (72)23 (79).5734 (67)
    Disease stage
     I28 (39)22 (61)6 (21).0010
     II43 (61)14 (39)23 (79)6 (100)
    Disease location
     Above diaphragm56 (79)32 (89)21 (72).1143 (50)
     Below diaphragm15 (21)4 (11)8 (28)3 (50)
     Mediastinal involvement3 (4)2 (6)1 (3)1.000
    ECOG PS
     064 (90)33 (92)27 (93)1.004 (67)
     17 (10)3 (8)2 (7)2 (33)
    B symptoms5 (7)04 (14).0351 (17)
    Extranodal disease4 (7)1 (3)3 (10).3160
    Histologic pattern
     Typical48 (68)28 (78)17 (59).1133 (50)
     Variant23 (32)8 (22)12 (41)3 (50)
    PET-CT imaging60 (85)29 (81)25 (86).7426 (100)
    Tumor size*
     Median (range), cm3.0 (1.2-8.5)3.0 (1.4-6.9)3.3 (1.2-8.5)2.8 (1.2-3.0)
     ≥5 cm8 (11)3 (8)5 (18).2820
    • Unless otherwise noted, all data are n (%).

    • ECOG PS, Eastern Cooperative Oncology Group Performance Status score.

    • * Tumor size was unavailable for 1 patient.

  • Table 2.

    Univariate analysis

    CharacteristicPFSOS
    HR (95% CI)PHR (95% CI)P
    Age1.01 (0.98-1.04).4251.05 (0.99-1.11).107
    Male3.73 (0.86-16.30).0801.65 (0.19-14.20).648
    Stage II1.26 (0.45-3.53).6652.4 (0.28-20.65).425
    ECOG PS 11.04 (0.30-3.62).9510.04 (0.00-265.72).461
    Supradiaphragmatic disease3.49 (0.80-15.24).09731.38 (0.01-85 218.00).393
    B symptoms0.63 (0.08-4.80).6300.05 (0.00-82 523.70).673
    Extranodal disease0.64 (0.08-4.90).6702.79 (0.32-24.07).351
    Variant histologic pattern0.65 (0.24-1.82).4170.39 (0.05-3.33).39
    PET-CT imaging not performed3.16 (1.24-8.04).0164.38 (0.74-25.88).104
    Tumor size ≥5 cm0.95 (0.27-3.34).9310.89 (0.10-7.65).913
    Era of therapy
     Before 2000*
     2000-20100.55 (0.20-1.50).2400.38 (0.08-1.97).251
     2011-20170.24 (0.03-2.22).210<0.01 (0.00-1.6 × 10172).957
    • HR, hazard ratio.

    • * The reference category is treatment before 2000.

  • Table 3.

    Treatment and outcome characteristics

    CharacteristicAll patients (N = 71)RT only (n = 36)Combined therapy (n = 29)RT-only vs combined therapy, PSystemic therapy (n = 6)
    Treatment
     Systemic only6 (9)
     Radiation only36 (51)
     Combined29 (41)
    Treatment era
     Before 20008 (11)6 (17)2 (7).4440
     2000–201030 (42)14 (39)11 (38)5 (83)
     2011–201733 (47)16 (44)16 (55)1 (17)
    Systemic therapy (n = 35)
     R-ABVD5 (7)4 (14)1 (17)
     R-CHOP22 (31)19 (66)3 (50)
     Rituximab5 (7)3 (10)2 (33)
     Other3 (4)3 (10)
    RT (n = 65)
     EFRT12 (17)9 (25)3 (10).088
     IFRT20 (28)13 (36)7 (24)
     ISRT33 (47)14 (39)19 (66)
    RT (n = 65)
     3-Dimensional39 (60)27 (75)12 (41).010
     Intensity-modulated RT26 (40)9 (25)17 (59)
    Radiation dose (n = 65)
     Median (range), Gy30.6 (21.6-40.0)36 (30-40)30.6 (21.6-40)
     >30.6 Gy32 (49)26 (72)6 (21)<.001
     ≤30.6 Gy33 (51)10 (28)23 (79)
    Death
     Yes6 (8)3 (8)2 (7)1 (17)
     No65 (92)33 (92)27 (93)5 (83)
    Relapse or progression
     Yes15 (21)8 (22)5 (17)2 (33)
     No56 (79)28 (78)24 (83)4 (67)
    Local relapse
     Yes2 (3)002 (33)
     No69 (97)36 (100)29 (100)4 (67)
    Distant relapse
     Yes13 (18)8 (22)5 (17)0
     No58 (82)28 (78)24 (83)6 (100)
    Transformation
     Yes2 (3)1 (3)1 (3).8760
     No69 (97)35 (97)28 (97)
    Second malignancy
     Yes8 (11)3 (8)5 (17).2770
     No63 (89)33 (92)24 (83)6 (100)
    Median follow-up (95% CI), y*6.1 (5.0-7.2)6.1 (3.3-8.9)4.4 (0.42–8.4).1747.5 (4.0-11.0)
    • Unless otherwise noted, all data are n (%).

    • * P value for comparison of all 3 groups is .341.

  • Table 4.

    Characteristics of disease relapses according to initial therapy

    All relapses (N = 15)RT only (n = 8)Combined therapy (n = 5)Systemic therapy only (n = 2)
    Isolated initial site
     Yes2 (13)002 (100)
     No13 (87)8 (100)5 (100)0
    Isolated distant
     Yes13 (87)8 (100)5 (100)0
     No2 (13)02 (100)
    Isolated contra-diaphragmatic
     Yes10 (67)7 (88)3 (60)0
     No5 (33)1 (12)2 (40)2 (100)
    Median time to relapse (range), mo6.2 (1.2-23.8)7.7 (2.8-15.7)6.2 (2.5-23.8)2.8 (1.2-4.5)
    Relapse >5 y from diagnosis10 (67)6 (75)4 (80)0
    • Unless otherwise noted, all data are n (%).