Early-Stage Hodgkin Lymphoma

Other regimens have been studied in hopes of reducing toxicity, including the EVE regimen (epirubicin, vinblastine, and etoposide). This regimen was compared to ABVD in early unfavorable Hodgkin lymphoma patients, with all patients undergoing the same RT program. No differences were observed between the ABVD and EVE arms in terms of complete remission rate and overall survival. However, patients who received EVE had a significantly worse outcome than those who received ABVD in terms of relapse-free survival and failure-free survival.⁸⁸ EBVP (epirubicin, bleomycin, vinblastine, and prednisone) followed by IFRT was less efficacious compared with MOPP/ABV–type therapy.⁵⁸

An area of active investigation is whether RT can be safely omitted in patients with early- stage unfavorable cHL. The EORTC H10 study showed that, for patients with a negative iPET scan (after 2 cycles), the 5-year PFS rates were 92.1% versus 89.6% for ABVD plus INRT versus ABVD alone, respectively. While this technically did not meet criteria for noninferiority of ABVD alone, this study demonstrated that, for those with negative iPET, ABVD × 6 cycles (without radiation) can result in long-term remission in a high proportion (89%) of patients. For iPET-positive patients, 2 cycles of escalated BEACOPP were given followed by 30 Gy of IFRT on the experimental arm. This resulted in a 5-year PFS of 90.6% versus 77.4%, suggesting this may be a preferred approach for early-stage unfavorable patients with a positive iPET.⁴⁸ Even though the noninferiority of ABVD alone could not be established based on the statistical design of the study, the current NCCN guidelines recommend restaging after 2 cycles of ABVD for stage I or II unfavorable cHL and using that iPET as a guide, based on Deauville scores. For scores 1–3, ABVD × 2 cycles (total 4 cycles) plus ISRT or AVD × 4 (total 6) with or without ISRT is recommended. For a Deauville score of 4, escalated BEACOPP × 2 cycles or ABVD × 2 cycles (total 4) followed by ISRT is recommended. If the Deauville score is 5, further treatment decisions should be made based on repeat biopsy results. A follow up PET/CT is recommended for Deauville scores of 4 and 5 to confirm complete response.⁴⁶

LATE EFFECTS AND THE EVOLUTION OF RADIATION THERAPY

The RT given in Hodgkin lymphoma has evolved considerably over the years, from extended field or subtotal nodal fields developed in the 1960s, to the more focused involved-field or even involved-site radiation commonly given now. This approach reduces radiation volumes, and it already is becoming evident that the relative risk of breast cancer among young females receiving mediastinal RT for Hodgkin lymphoma is declining.⁸⁹ Cardiac dose is reduced significantly with IFRT compared to older radiation techniques as well. The extent of radiation may be reduced even further with involved-nodal/involved site or intensity-modulated approaches.⁹⁰

With new RT techniques allowing for more focused therapy and lower doses of radiation, models predict that the rate of long-term complications will decline further.^91,92 Furthermore, response-adapted (ie, PET-directed) approaches, as discussed in detail earlier in the article, are expected to increasingly allow for identification of patients who can safely avoid radiation entirely, which will hopefully lead to an even lower rate of late complications of therapy.

MONITORING FOR RELAPSE

A number of recent studies have shown that, for patients who achieve complete remission with first-line therapy, performing repeated scheduled surveillance imaging does not improve outcomes. In fact, most relapses are detected by the patient (due to symptoms or recurrence of lymph node enlargement). It is rare that a relapse would be detected by surveillance imaging alone. Furthermore, surveillance that includes routine imaging has not been associated with improved survival.⁹³ As a result, it is now recommended that patients undergo regular follow-up with symptom review, physical exam, and basic laboratory studies. Imaging studies should be obtained as needed for patients who develop signs, symptoms, exam findings, or laboratory values concerning for relapse.

More important than scheduled surveillance imaging for relapse is monitoring for late effects of therapy. These fall into several broad categories such as cardiovascular disease (coronary disease, congestive heart failure, valvular disease, carotid artery disease), pulmonary disease, hypothyroidism, and secondary malignancies. Aggressive surveillance for breast cancer is especially warranted in female patients who underwent chest radiation.⁴⁶

CONCLUSION

Hodgkin lymphoma is characterized pathologically by the presence of HRS cells accompanied by a polymorphous cellular infiltrate. It is a disease with a bimodal age distribution, several pathologic subtypes, and numerous treatment options. Overall, the prognosis for patients with early-stage disease is excellent, and although a majority of patients can now be cured, further studies are needed to optimize treatment such that short- and long-term treatment-related toxicities are minimized, without compromising disease control and cure.