Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor 11/2019
Patients classified as having stage I or IIA Hodgkin Lymphoma (HL) are considered to have early stage disease and are almost always curable. For the purpose of treatment selection patients can be segregated into two groups based on the presence of the following “higher risk” features.
- B symptoms (unexplained fever ≥38°C, soaking night sweats, unexplained weight loss ≥10% within 6 months).
- Extra-nodal disease.
- Bulky disease (≥10 cm or >33% of the chest diameter on chest x-ray).
- Three or more sites of nodal involvement.
- Sedimentation rate of 50 mm/h or higher.
Individuals without these features are effectively treated with a shorter course of chemotherapy with ABVD (doxorubicin, bleomycin, Velban, and dacarbazine) followed by local radiation treatment which consistently cures over 95% of patients with stage I or IIA HL. (2) Clinical trials have determined that ABVD for 4 cycles or ABVD for two cycles plus “involved field” radiation directly to areas of cancer cures the majority of early stage HL patients. (3,4)
Patients with “higher risk” features and symptoms are typically treated as though they have advanced stage disease and are still cured the majority of the time; they do however require more chemotherapy; 4 cycles of ABVD + radiation or 6 cycles of ABVD. (8)
The goal of treatment for early stage HL is cure and to limit treatment-related side effects as much as possible. Historically, patients with stage I or IIA disease were successfully treated with radiation therapy alone. Radiation therapy is a “local” therapy and unable to kill cancer cells outside its field of delivery. Therefore, patients with HL had to undergo extensive staging with surgery, as well as removal of the spleen (staging laparotomy) to ensure that the cancer could be adequately treated with radiation therapy alone.
Full doses of radiation therapy cause significant long-term side effects to many patients. (1) Chemotherapy is more capable of curing early and advanced stage HL because unlike radiation it kills cancer cells anywhere in the body. The long-term side effects of chemotherapy are also less severe than those caused by radiation therapy. Currently most patients with stage I or IIA disease are treated with a combination of chemotherapy and radiation therapy in reduced doses. By utilizing combination therapy, high cure rates can be achieved, and the long-term side effects of each treatment may be decreased. Additionally, the extensive surgical staging evaluation can be avoided.
Methods to Detect Residual Lymphoma: Doctors monitor the response to treatment by checking for residual HL on CT or MRI scans after initial treatment. The presence of a residual mass can create problems for management because the mass may represent active HL or merely be scar or dead tissue from chemotherapy damage. PET (positron emission tomography) scanning helps doctors more accurately determine the presence of residual HL following treatment.
PET scans detect live cancer tissue. Prior to a PET scan, the patient receives an injection of a substance that contains a type of sugar attached to a radioactive isotope. The cancer cells “take up” the sugar and attached isotope, which emits positively charged, low energy radiation (positrons). The positrons react with electrons in the cancer cells, which creates the production of gamma rays. The gamma rays are then detected by the PET machine, which transforms the information into a picture. If no gamma rays are detected in the scanned area, it is unlikely that the mass in question contains living cancer cells. Doctors have demonstrated that PET scans are more effective in detecting residual cancer than CT scans. (5,6)
Strategies to Improve Treatment
The major area of active research aimed at improving the treatment of early stage HL is focused on reducing the intensity of treatment to avoid long term side effects especially in children.
Adcetris: Modified versions of ABVD chemotherapy with elimination of dacarbazine, bleomycin, or both have been attempted but outcomes were significantly worse. ABVD remains the standard chemotherapy regimen, however replacement of Bleomycin with the precision cancer medicine Adcetris in advanced stage HL has been shown to be superior to ABVD and this approach may further improve treatment of early stage HL as well. (7)
PET Monitored Therapy: One predictor of HL recurrence risk is the interim metabolic response as determined through PET scanning following the second cycle of ABVD chemotherapy. An inability to achieve complete response after the second cycle is associated with a higher risk of recurrence and shorter survival. Doctors continue to evaluate the use go PET to adjust therapy in clinical trials.
- Dores GM, Metayer C, Curtis RE, et al.: Second malignant neoplasms among long-term survivors of Hodgkin's disease: a population-based evaluation over 25 years. J Clin Oncol 20 (16): 3484-94, 2002.
- Duggan D, Petroni G, Johnson J, et al. Randomized comparison of ABVD and MOPP/ABV hybrid for the treatment of advanced Hodgkin’s disease: report of an Intergroup trial.
- Engert A, Franklin J, Eich HT, et al.: Two cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine plus extended-field radiotherapy is superior to radiotherapy alone in early favorable Hodgkin's lymphoma: final results of the GHSG HD7 trial. J Clin Oncol 25 (23): 3495-502, 2007.
- Meyer RM, Gospodarowicz MK, Connors JM, et al.: ABVD alone versus radiation-based therapy in limited-stage Hodgkin's lymphoma. N Engl J Med 366 (5): 399-408, 2012.
- Raemaekers JM, André MP, Federico M, et al.: Omitting radiotherapy in early positron emission tomography-negative stage I/II Hodgkin lymphoma is associated with an increased risk of early relapse: Clinical results of the preplanned interim analysis of the randomized EORTC/LYSA/FIL H10 trial. J Clin Oncol 32 (12): 1188-94, 2014
- 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 372 (17): 1598-607, 2015.
- Connors JM, Jurczak W, Straus DJ, et al; ECHELON-1 Study Group. Brentuximab vedotin with chemotherapy for stage III or IV Hodgkin’s lymphoma. N Engl J Med. 2018;378(4):331-344.