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Early stage Hodgkin's lymphoma risk stratification (EORTC, GHSG, NCCN criteria)

Risk stratification of
early stage Stage I or II according to the Ann-Arbor classification.

Stage I:
Nodal involvement in a single lymph node region OR a single localized extranodal involvement (outside the lymphatic system)

Stage II:
Nodal involvement in two or more lymph node regions on one side of the diaphragm OR localized extranodal involvements (outside the lymphatic system) in two or more regions on one side of the diaphragm.
Hodgkin lymphoma guides prognosis and treatment strategy. The risk stratification criteria according to the EORTC, GHSG and NCCN vary slightly in content. This tool provides an easy method to compare the risk status of a patient across these three risk stratification protocols.

1. Select risk stratification criteria:


EORTC European Organisation of Research and Treatment of Cancer criteria

GHSG German Hodgkin Study Group criteria

NCCN National Comprehensive Cancer Network criteria

Mediastinal mass:
Mediastinal mass:thoracic ratio of <0.35 or no mediastinal mass
Mediastinal mass:thoracic ratio of ≥0.35
Age (years):
< 50
≥50
ESR: Erythrocyte sedimentation rate.
B-symptoms: Fevers, nights sweats or weight loss
< 50mm/h without B-symptoms
OR
<30mm/h with B-symptoms
≥ 50mm/h without B-symptoms
OR
≥30mm/h with B-symptoms
Number of nodal sites: The EORTC criteria are based on supradiaphragmatic early stage disease

The five nodal areas according to EORTC criteria are:
  • The whole neck including supraclavicular area (left and right separately)

  • The axilla including the infraclavicular area (left and right separately)

  • The mediastinum including hilar lymph nodes on both sides (one area)
< 4 sites
≥ 4 sites
Stage As per the Ann-Arbor classification:

Stage I:
Nodal involvement in a single lymph node region OR a single localized extranodal involvement (outside the lymphatic system)

Stage II:
Nodal involvement in two or more lymph node regions on one side of the diaphragm OR localized extranodal involvements (outside the lymphatic system) in two or more regions on one side of the diaphragm.

A= No B-symptoms
B= B-symptoms present (fevers, nights sweats or weight loss)
I or IIA
IIB
Mediastinal mass:
Mediastinal mass:thoracic ratio of <0.33 or no mediastinal mass
Mediastinal mass:thoracic ratio of ≥0.33
Extra-nodal disease: Any tumor spread involving tissue outside of the lymph nodes, spleen, thymus, Waldeyer’s tonsillar ring, appendix and Peyer’s patches.
No
Yes
ESR: Erythrocyte sedimentation rate.
B-symptoms: Fevers, nights sweats or weight loss
< 50mm/h without B-symptoms
OR
<30mm/h with B-symptoms
≥ 50mm/h without B-symptoms
OR
≥30mm/h with B-symptoms
Number of nodal areas: A lymph node area may involve more than one Ann-Arbor nodal region.

The lymph node areas as per GHSG are:
  • Area A: right cervical + right infra-/supra-clavicular/nuchal lymph nodes
  • Area B: right cervical + right infra-/supra-clavicular/nuchal lymph nodes
  • Area C: right/left hilar + mediastinal lymph nodes
  • Area D: right axillary lymph nodes
  • Area E: left axillary lymph nodes
  • Area F: lymph nodes of the upper abdomen (spleen hilum, liver hilum, coeliacal)
  • Area G: lymph nodes of the lower abdomen
  • Area H: right iliac lymph nodes
  • Area I: left iliac lymph nodes
  • Area K: right inguinal + femoral lymph nodes
  • Area L: left inguinal + femoral lymph nodes
< 3 sites
≥ 3 sites
Mediastinal mass:
Mediastinal mass:thoracic ratio of <0.33 or no mediastinal mass
Mediastinal mass:thoracic ratio of ≥0.33
ESR: Erythrocyte sedimentation rate.
< 50mm/h
≥ 50mm/h
B-symptoms: Fevers, nights sweats or weight loss
No
Yes
Number of nodal sites:
< 4 sites
≥ 4 sites
Adenopathy ≥10cm:
No
Yes
IPS score:

Early stage (I, II) classical Hodgkin's lymphoma risk stratification (EORTC, GHSG, NCCN criteria)

Patients with early stage classical Hodgkin's lymphoma should be risk stratified according to the EORTC, GHSG or NCCN criteria, to inform prognosis and treatment strategy.

There are differences in the risk factors included in each working group's criteria. Of note the GHSG criteria considers patients with stage IIB disease and a large mediastinal mass (≥one third of thoracic diameter) or extranodal disease as advanced stage disease and recommends such patients are managed according to advanced disease guidelines.

A number of clinical trials have been conducted in the setting of early stage classical Hodgkin lymphoma. A combined modality approach consisting of chemotherapy and involved site radiotherapy has been found to result in improved progression free survival (PFS) in a number of trials(1–5).

However this has to be balanced against the risk of late effects of radiotherapy including increased risk of second malignancy. In some instances, a chemotherapy only approach may be preferred e.g. young female patients with axillary/ mediastinal disease at risk of secondary breast cancer from radiotherapy. Therefore, involvement of the multidisciplinary team and discussion of risks versus benefits is important in decision making.

A summary of treatment options guided by risk status is provided below to illustrate the utility of risk stratification in management. Treatment paradigms are constantly evolving and latest NCCN, ESMO and national guidelines should be reviewed for current recommendations.

Treatment options for early stage favorable risk:
2x ABVD followed by interim PET.
If interim PET negative:
1x further ABVD followed by 30Gy ISRT (Evidence: EORTC H10 trial and adapted from the RAPID trial(3,4))

OR if favorable risk according to GHSG criteria:
20Gy ISRT (Evidence: GHSG HD10 trial(6))

OR if chemotherapy alone strategy preferred:
2x further ABVD (Evidence: EORTC H10 trial(4) noting reduction in PFS from 99% to 87% when RT was omitted, CALGB 50604 trial(7)).

If interim PET positive:
2x escalated BEACOPP followed by 30Gy ISRT (EORTC H10 trial)

ABVD = doxorubicin, bleomycin, vinblastine, and dacarbazine ISRT = Involved site radiotherapy BEACOPP = bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisolone

Treatment options for early stage unfavorable risk:
Option 1:
2x ABVD followed by interim PET.
If interim PET negative:
2x further ABVD followed by 30Gy ISRT (Evidence: EORTC H10 trial(4))
OR if chemotherapy alone strategy preferred:
4x further AVD (Evidence: adapted from RATHL trial (8))

If interim PET positive:
2x escalated BEACOPP + 30Gy ISRT (Evidence: EORTC H10 trial(4))

Option 2 (Evidence: GHSG HD17 trial(9)):
2x escalated BEACOPP + 2x ABVD followed by interim PET
If PET negative:
No further treatment
If PET positive:
30Gy ISRT

References:
  1. Fermé C, Eghbali H, Meerwaldt JH, et al. Chemotherapy plus involved-field radiation in early-stage Hodgkin’s disease. N Engl J Med. 2007;357(19):1916-1927. doi:10.1056/NEJMoa064601
  2. Sasse S, Bröckelmann PJ, Goergen H, et al. Long-Term Follow-Up of Contemporary Treatment in Early-Stage Hodgkin Lymphoma: Updated Analyses of the German Hodgkin Study Group HD7, HD8, HD10, and HD11 Trials. J Clin Oncol Off J Am Soc Clin Oncol. 2017;35(18):1999-2007. doi:10.1200/JCO.2016.70.9410
  3. Radford J, Illidge T, Counsell N, et al. Results of a Trial of PET-Directed Therapy for Early-Stage Hodgkin’s Lymphoma. N Engl J Med. 2015;372(17):1598-1607. doi:10.1056/NEJMoa1408648
  4. André MPE, Girinsky T, Federico M, et al. Early Positron Emission Tomography Response-Adapted Treatment in Stage I and II Hodgkin Lymphoma: Final Results of the Randomized EORTC/LYSA/FIL H10 Trial. J Clin Oncol Off J Am Soc Clin Oncol. 2017;35(16):1786-1794. doi:10.1200/JCO.2016.68.6394
  5. Fuchs M, Goergen H, Kobe C, et al. Positron Emission Tomography-Guided Treatment in Early-Stage Favorable Hodgkin Lymphoma: Final Results of the International, Randomized Phase III HD16 Trial by the German Hodgkin Study Group. J Clin Oncol Off J Am Soc Clin Oncol. 2019;37(31):2835-2845. doi:10.1200/JCO.19.00964
  6. Engert A, Plütschow A, Eich HT, et al. Reduced Treatment Intensity in Patients with Early-Stage Hodgkin’s Lymphoma. N Engl J Med. 2010;363(7):640-652. doi:10.1056/NEJMoa1000067
  7. Straus DJ, Jung S-H, Pitcher B, et al. CALGB 50604: risk-adapted treatment of nonbulky early-stage Hodgkin lymphoma based on interim PET. Blood. 2018;132(10):1013-1021. doi:10.1182/blood-2018-01-827246
  8. Johnson P, Federico M, Kirkwood A, et al. Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin’s Lymphoma. N Engl J Med. 2016;374(25):2419-2429. doi:10.1056/NEJMoa1510093
  9. Borchmann P, Plütschow A, Kobe C, et al. PET-guided omission of radiotherapy in early-stage unfavourable Hodgkin lymphoma (GHSG HD17): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2021;22(2):223-234. doi:10.1016/S1470-2045(20)30601-X