Brian was a 20-year old college basketball star who was in excellent condition and had no history of health problems. He grew up in a tough neighborhood with a single mother who raised him to be a fine young gentleman. He was awarded a basketball scholarship to state college, where he became the league leading scorer during his junior year. When his mother came to visit for a game late in the season, she noticed that Brian’s neck appeared much larger on one side than the other. The next day, she convinced him to see the college physician who felt multiple enlarged lymph nodes in his right neck extending from the angle of the jaw down to just above his collarbone. The doctor ordered a CT scan of the neck and chest that confirmed multiple abnormal lymph nodes in the right side of the neck as well as the center of the chest. Brian was referred to a general surgeon who removed one of the larger lymph nodes in his neck during an outpatient surgery. This excisional biopsy revealed Hodgkin lymphoma.
Following his diagnosis, Brian was sent for a bone marrow biopsy which was negative. He also underwent a PET/CT scan that confirmed abnormal activity in the right neck and chest in multiple lymph nodes. Brian was referred to a medical oncologist who recommended treatment with ABVD chemotherapy. He received 4 cycles which he tolerated very well, with only moderate fatigue. A restaging PET/CT scan revealed no residual abnormal activity. He was seen by a radiation oncologist who recommended low dose involved field radiation therapy (IFRT) after chemotherapy which was delivered over 3 weeks. Other than a mild sore throat, Brian tolerated RT quite well. He was seen every 3-6 months by his medical and radiation oncologist for alternating follow-up visits. Brian has been free of disease for 7 years.
Hodgkin’s lymphoma (HL) is much less common than non-Hodgkin lymphoma (NHL), though it may be diagnosed in children as well as the elderly. If the disease is localized, then the 5-year survival is over 90%. Even patients with more advanced HL have a 5-year survival rate of 75-80%
RISKS & CAUSES
People who have history of a first degree relative diagnosed with HL are at a significantly increased risk of developing the disease themselves. In addition, patients who have Epstein-Barr virus (EBV) infection early in life appear to have an increased risk of HL later in life. There appears to be a correlation with patients of low socioeconomic status also.
SIGNS & SYMPTOMS
The vast majority of patients with HL will come to the doctor with the complaint of an enlarged lymph node or multiple lymph nodes that won’t go away. Most frequently the node will arise in the neck, but may also be felt in other common lymph node areas including the axilla (under the arm) and the groin. Doctors should also ask questions regarding unexplained weight loss, fevers, or drenching night sweats, the “B symptoms” that are classic for lymphoma. Although they are only present in a subset of patients, B symptoms tend to predict for more advanced disease. Rarely, patients may present with diffuse itching or flushing of the skin when drinking alcohol as an initial sign of HL.
Like NHL, the preferred method of biopsy for HL is complete surgical removal of an enlarged lymph node (excisional biopsy) whenever feasible and safe. There are multiple subtypes of HL including: nodular sclerosing, mixed cellularity, lymphocyte rich and lymphocyte depleted. Yet another subtype, called nodular lymphocyte predominant HL, appears to be biologically different from the others, but also has an extremely high cure rate.
Standard laboratory evaluation should include complete blood count, serum chemistries including kidney and liver function, blood levels of lactate dehydrogenase (LDH) and erythrocyte sedimentation rate (ESR), the latter two of which have been shown to predict for more advanced disease when elevated. As with NHL, the Ann Arbor staging system is used. This system is based on the number and sites of involvement in lymph nodes and other organs, as well as the presence or absence of B symptoms. Imaging should include CT of involved areas including neck, chest, abdomen and pelvis. Wherever available, PET/CT is extremely useful for staging, radiation therapy (RT) planning, and assessing response to treatment. Bone marrow biopsies are indicated for patients with advanced disease including those who present with B symptoms. Other factors that may negatively impact outcome include male sex, age older than 45, low serum hemoglobin, high white blood cell count, low albumin, and stage IV disease.
Like NHL, HL is treated with a combination of chemotherapy drugs. In the case of HL, four drugs are utilized most commonly in the United States: adriamycin, bleomycin, vinblastine, and dacarbazine. The acronym for the combination is ABVD. Treatment of tens of thousands of patients over the past few decades with ABVD has shown consistently excellent results.
Patients with early stage HL generally receive 2-6 cycles of ABVD. Restaging imaging is obtained after 2-4 cycles to guide further treatment. PET restaging is predictive of outcome. The combination of ABVD followed by involved field radiation therapy (IFRT) yields an excellent chance for cure.
Common acute side effects of ABVD include fatigue, nausea (usually well-controlled with medication), mild anorexia, decreased blood counts, and hair loss. Uncommon but serious late side effects following treatment include heart damage from adriamycin, lung damage from bleomycin, and nerve damage from vinblastine. Chemotherapy does put patients at a slightly increased risk for development of future cancers, most commonly leukemia or NHL.
Since low doses and fairly small treatment areas are currently utilized for IFRT, side effects are much less than decades ago when the doses were higher and treatment areas were larger. Common acute side effects of IFRT include mild fatigue, possible partial alopecia (hair loss), and sore throat or difficulty swallowing, depending on the area treated. There is a risk of pneumonitis (inflammation of the lung) characterized by low-grade fever, dry cough, and shortness of breath with exertion, that occurs classically 1-3 months after RT. The 5-10% of patients who develop lung inflammation usually have resolution of their symptoms within 3-4 weeks after start of steroids. Long-term, despite the low doses and small RT fields, there remains a small risk of developing a radiation-induced cancer years after treatment. Patients should be encouraged to quit smoking prior to RT. Teenage girls and young women who require RT to the chest should begin annual mammogram (and usually breast MRI) screening within 7-10 years following treatment or at age 40, whichever comes first.
Advanced stage HL is treated most commonly with systemic chemotherapy alone, again predominantly ABVD in the U.S. Cure rates are about 70%. Patients may receive 6-8 cycles of ABVD, with restaging PET/CT performed after 4-6 cycles to assess response. The role of consolidative IFRT for these patients is controversial.