Concurrent Deep Locoregional Thermal Therapy With Pencil Beam Scanning Proton Therapy Results In Modest Toxicity With The Promise Of Increased Efficacy

Thermal therapy at 39-44°C has a well-documented ability to increase the efficacy of radiotherapy (RT) by inhibition of DNA repair and through improved tumoral oxygenation. Our prior presentation did not demonstrate increased acute toxicities; however, little remains known about the safety and feasibility of Proton Beam Therapy (PBT) and Deep Thermal Therapy (DTT). With continued follow up of patients treated more than a year ago, we hypothesize this dual-modality treatment is safe and feasible. We performed a retrospective IRB-approved single-institution review of all patients treated with PBT and concurrent DTT. Patient and disease characteristics were collected along with RT dose and DTT parameters: maximum thermal dose (TDmax) measured with cumulative equivalent minutes at 43°C (CEM43) and maximum temperature (Tmax). The minimum temperature goals of 40°C (tumor) and 39°C (tumor surrogate) were used to determine therapeutic treatment time, with a goal of 45-60 min per treatment. Temperatures were recorded in target (tumor/surrogate) and normal tissue using 1-3 and 5-7 sensors, respectively. Combination DTT+PBT treatment was delivered to 27 patients with a median age of 66 (range, 19-78 years). Most common histologies included colorectal (n = 15), prostate (n = 6), and bladder (n = 3). 22 patients (81.5%) were treated for locally recurrent disease and 20 (74.1%) were treated with re-irradiation. Median PBT dose was 48.0 Gy(RBE) (30-66 Gy[RBE]) with one patient receiving PBT+HDR for recurrent cervical cancer. Twice daily radiation was used in 13 (48.1%) and eight (29.6%) received concurrent chemotherapy with DTT and PBT. 163 DTT treatments were completed with the following medians (ranges): 6 (1-14) treatments per patient; therapeutic time of 39 min (0-60 min); and net power of 605 W (381-1114 W). The target Tmax achieved on average 41.4°C (38.3-43.7°C) which corresponded to a TDmax average of 4.5 CEM43 (0-25.5 CEM43). Healthy tissue Tmax ranged from 35.9°C to 42.5°C and the correspondent TDmax varied from 0 to 14.4 CEM43. Seven (25.9%) discontinued DTT early due to treatment related pain. Acute toxicities included grade 1-2 pain (n = 14), diarrhea (n = 7) and dermatitis (n = 5). There was one patient with transient lymphedema due to tumoral edema and compression of iliac vessels which resolved during treatment. With a median follow up of 9 months (range, 1-15 months) there have been 4 reported local failures to date at a median of 6 months (range 4-11). Updated toxicities and outcomes will be presented. Initial combination of PBT with DTT is well tolerated and our experience now does not show increased subacute toxicities from expectations given this is a high-risk population. Continued follow up is required to assess late toxicities and treatment related outcomes.