Treatment for Stages I - IIA Hodgkin Lymphoma
Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor (08/2018)
Patients classified as having stage I or II A disease are considered to have early stage Hodgkin’s lymphoma and are almost always curable. Patients considered to have early stage cancer do not have any “B” symptoms or “bulky” disease. Bulky sites of cancer are those greater then 10 centimeters in diameter. On careful examination, patients with “B” symptoms will often have a higher stage; therefore, patients with “B” symptoms are typically treated as though they have advanced stage disease.
The majority of patients diagnosed with Hodgkin’s disease can expect to be cured of their cancer when modern treatment strategies are appropriately utilized. Many different treatment strategies can cure patients with stage I or IIA Hodgkin’s lymphoma. The current goal of treatment is to cure patients, but 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 unable to kill cancer cells outside its field of delivery. Therefore, patients with Hodgkin’s lymphoma 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 also cause significant long-term side effects to many patients.
Chemotherapy is also capable of curing early and advanced stage Hodgkin’s lymphoma. Chemotherapy has an advantage over radiation therapy because it kills cancer cells anywhere in the body. The long-term side effects of chemotherapy may also be less severe than those caused by radiation therapy. Recently, patients with stage I or IIA disease have been 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. Currently, a short duration of chemotherapy with ABVD (doxorubicin, bleomycin, Velban®, and dacarbazine) followed by local radiation treatment consistently cures over 95% of patients with stage I or IIA Hodgkin’s lymphoma.
Doctors in Germany designed and conducted a clinical trial that combined chemotherapy with radiation therapy and compared this to treatment with radiation therapy alone. In this clinical study, 640 patients with stage I or II Hodgkin’s lymphoma who were at a low risk of cancer recurrence were treated with radiation therapy alone or 2 cycles of chemotherapy with ABVD (doxorubicin, bleomycin, Velban®, and dacarbazine) followed by treatment with radiation.
The first interim analysis of this clinical trial has been performed in approximately 400 patients, with a minimum of almost 2 years of follow-up from treatment. This analysis shows that patients treated with the combination of chemotherapy and radiation therapy were less likely to experience cancer recurrence than patients treated with radiation therapy alone. Only one patient treated with the combination of chemotherapy and radiation therapy has experienced recurrence of cancer and 96% of patients are alive without evidence of cancer recurrence 2 years from treatment. In comparison, 17 patients treated with radiation therapy alone have experienced cancer recurrence and only 87% are alive without evidence of cancer recurrence 2 years from treatment. Analysis comparing the side effects will be forthcoming; however, both treatment approaches appear to be well tolerated.
In summary, the results of this clinical study strongly suggest that patients with early stage Hodgkin’s disease are likely to experience a higher cure rate if treated with 2 cycles of chemotherapy followed by radiation therapy compared to the historical standard treatment of radiation therapy alone.
Improved Methods to Detect Residual Lymphoma: The appearance of a residual mass after initial treatment of lymphoma can create problems for management because the mass may represent active cancer or merely be scar or dead tissue from chemotherapy damage. The usual method of evaluating a residual mass is with repeated CT scans or surgical biopsy. CT scans have not been very effective at recognizing cancer versus scar or dead tissue since they only recognize an abnormal mass. Often, a surgical biopsy is necessary to determine whether cancer remains. PET (positron emission tomography) scanning may help doctors more accurately determine the presence of residual cancer following treatment.
A PET scan is similar to a CT scan; however, PET scans can 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 in Belgium recently reported that PET scans were more effective in detecting residual cancer than CT scans. In patients with Hodgkin’s disease, relapse occurred in 100% of patients with a residual mass detected on a PET scan, compared to only 26% of patients with a residual mass on a CT scan. In the future, PET scans should help identify patients who need further treatment after initial treatment.
Complications of Treatment for Hodgkin’s Lymphoma
One of the major side effects of treatment of Hodgkin’s lymphoma is the development of a second cancer. These second cancers are caused by the radiation, chemotherapy or the combination of radiation and chemotherapy used to treat Hodgkin’s lymphoma. In one clinical study evaluating the risk of second cancers in over 5,500 patients treated for Hodgkin’s lymphoma, there were 322 second cancers. Thus 6% pf all treated patients developed a second cancer. In another study of 420 patients, the risk of developing a second cancer 15 years following treatment was 11.7%. These included cancers of the gastrointestinal tract, lung, breast, bone, soft tissue and leukemia.
Strategies to Improve Treatment
The progress that has been made in the treatment of early stage Hodgkin’s lymphoma has resulted from improved pre-treatment staging of the cancer, development of new chemotherapy treatment regimens and patient/doctor participation in clinical trials. Future progress will result from continued participation in appropriate clinical trials.
The major areas of active research aimed at improving the treatment of early stage Hodgkin’s lymphoma focus on determining the type and extent of radiation therapy that is necessary as part of the treatment plan. Other clinical trials comparing short duration chemotherapy and radiation to chemotherapy alone are ongoing to determine whether radiation is necessary for any patients.
Development of Less Toxic Regimens for Children: Hodgkin’s disease in children is a relatively rare cancer with a high cure rate. Because of the high cure rate with chemotherapy and radiation, a major focus of researchers over the past decade has been to attempt to reduce the long-term side effects of therapy while maintaining the high cure rate. Long-term side effects of chemotherapy and radiation may include sterility, cataracts and the development of new cancers.
Physicians from Germany and Austria performed a multi-center clinical trial to evaluate changes in the standard combination chemotherapy regimen, with the goal of decreasing long-term side effects. This clinical trial involved 319 boys and 259 girls with Hodgkin’s disease treated between 1990 and 1995. Based on staging, the cancer was categorized as early, intermediate or advanced. The treatment program consisted of Oncovin®, prednisone, procarbazine, and doxorubicin or cyclophosphamide, Oncovin®, prednisone, and procarbazine chemotherapy with or without radiation. In the boys, a commonly used chemotherapy agent called etoposide was substituted for procarbazine in order to prevent damage to the testes. In addition, both the size of the radiation fields and the dose of radiation were decreased. These changes were expected to reduce side effects without affecting the cure rate.
Five years from initiation of treatment, 91% of children survived without evidence of cancer recurrence and 98% of children were alive. Importantly, the doctors found that etoposide could be substituted for procarbazine in the treatment regimen without increasing the rate of cancer relapses and that radiotherapy could be confined to sites involved with cancer when combined with chemotherapy. With these changes, boys were less likely to experience side effects to the testes.
These physicians concluded that this regimen provided adequate treatment for all stages of Hodgkin’s disease in children, resulting in excellent disease control and a reduction in long-term side effects. Additional studies are ongoing in early stage Hodgkin’s disease in order to further refine treatment and determine whether radiation therapy can be completely omitted without compromising long-term cure rates.