Primary Gastric Diffuse Large B-Cell Lymphoma Treated with Abbreviated Chemoimmunotherapy and Contemporary Radiation Therapy has Excellent Outcomes with Minimal Toxicity

Abstract

The gastrointestinal tract is the most common location for extranodal involvement of diffuse large B-cell lymphoma (DLBCL). We sought to evaluate outcomes and toxicities for patients with primary gastric DLBCL, treated with modern radiation therapy (RT). We performed dosimetric comparisons for two motion management strategies (4-dimensional computed tomography, 4DCT and deep inspiration breath hold, DIBH), in an effort to define the utility of advanced RT techniques. We evaluated 20 patients treated at a single institution with chemoimmunotherapy and involved site radiation therapy (ISRT) for early stage (IE – IIE) gastric DLBCL from 2009 to 2016. We included patients who had response on PET-CT during or after chemoimmunotherapy. We measured progression free survival (PFS), overall survival (OS), and local control (LC) using the KM method. Toxicities were extracted from the medical chart per CTCAE v4.0. Additionally, we report dosimetric parameters for patients treated to an internal target volume (ITV) created using 4DCT versus several DIBH images. We specifically examined dose to the heart (mean, V30, V20, V10, and V5). A paired two sided t-test was performed to compare these results. The median age was 66 years (IQR: 54 – 77), 13 patients (65%) had stage I disease. 90% of patients received R-CHOP and 10% (n=2) received dose adjusted R-EPOCH. The median number of chemotherapy cycles was 4, 55% (n=11) had 3-4 cycles of chemotherapy and 45% (n=9) had 6 cycles. All patients were treated with intensity modulated radiation therapy (IMRT) and image guided radiotherapy (IGRT, CT in 18, kV in 2). The median RT dose was 30.6 Gy (range 30-36 Gy). The median follow up for the cohort from date of diagnosis was 42 months (IQR: 27 – 69). At 4 years, the PFS, OS, and LC for the cohort were 82%, 89%, and 100% respectively. Only one patient experienced relapse (thyroid gland). Two patients died due to intercurrent disease. There were no grade 2 or higher acute toxicities. One patient developed a late grade 3 gastric outlet obstruction. The CTV comprised the entire stomach. For five patients, ITVs were generated using both 4DCT and DIBH CT images. A uniform 1 cm PTV expansion was used. Using 4DCT instead of DIBH images for planning resulted in significant increases in cardiac doses. The mean heart dose for DIBH was 2.9 Gy compared to 5 Gy for 4DCT (p=0.04). The volume of the heart that received 10 Gy and 5 Gy was also increased for 4DCT (p=0.04 and p=0.03, respectively). For early stage gastric DLBCL, chemoimmunotherapy followed by ISRT yields excellent outcomes, even after abbreviated systemic therapy. Radiation was well tolerated with minimal reported toxicity using modern IMRT/IGRT. IMRT delivered with DIBH can significantly reduce cardiac doses and should be considered at centers with breath hold technology.