Omission Of Cardiophrenic Lymph Nodes In The Treatment Of Patients With Hodgkin Lymphoma Using Modified Involved Site Radiation Therapy: Lower Toxicity With No Added Failure

Cardiophrenic lymph node (CPLN) involvement is relatively infrequent pattern of involvement at diagnosis among patients with Hodgkin lymphoma (HL). Targeting the CPLN region with radiation therapy (RT) can lead to potentially increased long term morbidity. We sought to 1) characterize the incidence of CPLN involvement and 2) evaluate the outcome of patients treated with RT and omission of the CPLN region from the RT field. We retrospectively reviewed the records of 169 consecutive patients treated with RT for HL between 2009 and 2015. Baseline PET-CT images were reviewed to identify CPLN involvement. RT fields were defined as: standard ISRT (S-ISRT), reduced dose-ISRT (RD-ISRT, defined as standard dose to most sites of disease and lower dose to the CPLN region) or modified-ISRT (M-ISRT, defined as total omission of the CPLN site from the RT field). The mean total dose, V25 and V5 of organs at risk (OAR) lung, heart, breasts, left ventricle (LV), right and left coronary arteries (CAs) were evaluated. Comparison plans were generated to evaluate the increased doses to OAR from M-ISRT compared to S-ISRT. Independent and paired two-sided t-tests were performed. P values ≤ 0.05 were significant. Among 169 patients, CPLN involvement was present in 17.1% (n = 29). The median number of CPLNs was 1 (range 1-8). Of patients with CPLN involvement, 69% were female and 55% had bulky mediastinal disease (n = 16). The median number of chemotherapy (CT) cycles was 6 (range 4-6). Nine of the 29 patients with CPLN(s) at diagnosis received RT for refractory disease. We analyzed the RT plans for the 20 patients that received RT after complete response to CT. Four patients (20%) were treated with S-ISRT, 8 (40%) with RD-ISRT and 8 (40%) with M-ISRT. At a median follow-up of 3.7 years from diagnosis (range 0.8-8.1 years), the 5-year progression free survival, and overall survival rates were 94.7% and 100%, respectively. One relapse occurred in non-CPLN sites in a patient that received RD-ISRT. Total heart V25 values for patients treated with S-ISRT were higher compared to M-ISRT (P = 0.056) and RD-ISRT (P = 0.038). Re-planning of M-ISRT cases with S-ISRT had the greatest impact on RT cardiac dose. The majority of dosimetric parameters of the heart, LV and CAs were significantly increased with S-ISRT planning. For instance, the total mean heart dose with M-ISRT was 11.8 Gy compared to 14.4 Gy with S-ISRT (P = 0.01). The V25 and V5 for the total heart were 25.8 % and 49.6% with M-ISRT compared to 30.8% and 65.1% with S-ISRT (P = 0.03 and P < 0.01, respectively). Lung dosimetric parameters were not significantly increased with S-ISRT planning of cases treated with M-ISRT. In this pilot study of modified ISRT, omission of CPLN was not associated with increased failure rates and resulted in significantly reduced radiation exposure to the heart.