Consolidative Proton Therapy in Patients with Hodgkin Lymphoma: Early Outcomes
Reporting Author: Abigail T. Berman, MD
Last Modified: June 10, 2013
Presenting Author: Bradford Hoppe, MD
Presenting Author Affiliation: University of Florida Proton Therapy Institute, Radiation Oncology, Jacksonville
- There are approximately 9000 cases of Hodgkin lymphoma diagnosed annually in the United States.
- The majority of patients are young adults, and 75-85% of patients will be cured with treatment consisting of chemotherapy +/- radiotherapy.
- However, the late effects of radiotherapy in this population are of great importance. At 25 years following treatment, 40% will have developed a grade 3 or higher late effect from their treatment including 2nd cancers or cardiac problems (Oeffinger NEJM 2006).
- Because of these late effects, there has been an increasing effort to reduce the dose to organs at risk include more conformal plans, including IMRT and proton therapy.
- This purpose of this study was to describe the early outcomes of patients with Hodgkin lymphoma (HL) treated with consolidative proton therapy following chemotherapy.
- Between September 2009 and January 2013, 22 patients with HL were treated with chemotherapy followed by proton therapy (PT) and were enrolled on an outcomes-tracking protocol.
- Eight patients were male, 14 were female, and the median age at diagnosis was 18 (range, 7-57). There were 9 pediatric patients and 13 adult patients.
- Stage distribution included I (n=2), II (n=11), III(n=4), IV(n=1), and relapsed/refractory disease (n=4).
- Twenty patients had mediastinal involvement and 16 were bulky.
- Nine pediatric patients received 15-25.5 CGE at 1.5CGE/fraction, 9 adults received 30.6-39.6 CGE at 1.8 CGE/fraction, and 4 relapsed/refractory patients received 30.6 CGE.
- Patients were evaluated weekly during treatment via CTCAE v3 toxicity, every 3 months for the first 2 years, then every 6 months for the subsequent 3 years.
- Progression-free (PFS) and event-free (EFS) survival rates were calculated by the Kaplan-Meier method.
- The median follow up for the entire cohort was 29 months (range, 5-48).
- Of the 4 patients with relapsed/refractory HL, there was one relapse following PT that occurred out-of-field.
- Among the other 18 patients, two events occurred, including 1 patient with transformation into a primary mediastinal B-cell lymphoma (20 yo F with stage IIB bulky HL with partial response s/p chemotherapy) and another with a combined in-field and out-of-field relapse.
- The two year PFS and EFS for these patients were 94% and 86%, respectively. The 2-year local control rate for all patients was 95%. No acute or late grade 3 toxicities occurred.
- Acute grade 2 toxicities included 3 patients with esophagitis and 3 with nausea. One patient with prior bleomycin pulmonary toxicity received prednisone for asymptomatic radiographic radiation pneumonitis. No late toxicities have occurred.
- Proton therapy following chemotherapy in patients with HL is well tolerated with results similar to conventional photon therapy.
- Larger patient numbers and longer follow up are needed to observe the advantages of proton therapy and its ability to reduce late toxicity.
- This is the largest clinical study to our knowledge to-date of proton therapy for HL. The authors show excellent local control and toxicity outcomes, similar to photon therapy.
- The main advantage for proton therapy in HL is reducing late toxicity, and, although not the goal of this report, the long-term outcomes will be crucial to investigate.
- Previous studies of photon beam therapy have shown an increase in the risk of breast cancer (relative risk [RR] 3.2 at dose > 4 Gy, Travis et al. 2002), lung cancer (RR 5.9 at dose >5 Gy, Travis et al. 2003), as well as cardiac complications (RR of 2.2-3.3 at dose >15 Gy, Mulrooney 2009).
- The dosimetric benefits of proton beam therapy have previously been shown. In females, if posterior beams are used, the breasts can be spared which should lead to a decrease the risk of secondary breast cancer. Alternatively, anterior beams can be used to spare the heart and lungs. Hoppe et al. previously reported the dosimetric benefits to the heart, lungs, and breast of involved-node proton therapy for Stage IA-IIIB mediastinal Hodgkin Lymphoma (IJROBP 2012).
- Involved-node RT has been studied prospectively by the British Columbia group (Campbell JCO 2008). Although not specifically stated, we assume that involved field radiotherapy, not involved node, was used. Even further reductions in toxicity may be possible if involved-node is deemed an acceptable radiotherapy technique to involved field.