Dose escalation with an IMRT technique in 15 to 28 fractions is better tolerated than standard doses of 3DCRT for LAPC

Abstract

PurposeTo review acute and late toxicities after chemoradiation for locally advanced pancreatic ductal adenocarcinoma in patients who were treated with escalated dose radiation (EDR).Methods and materialsMaximum Common Terminology Criteria for Adverse Events Version 4.0 acute toxicities (AT) during radiation and within 60 days after radiation were recorded for both acute gastrointestinal toxicity and overall toxicity (OT). Late toxicities were also recorded. EDR was generally delivered with daily image guidance and breath-hold techniques using intensity modulated radiation therapy (IMRT) planning. These were compared with patients who received standard dose radiation (SDR) delivered as 50.4 Gy in 28 fractions using 3-dimensional chemoradiation therapy planning.ResultsA total of 59 of 154 patients (39%) received EDR with biologically equivalent doses >70 Gy. The most frequent schedules were 63 Gy in 28 fractions (19 of 154 patients), 67.5 Gy in 15 fractions (10 of 154 patients), and 70 Gy in 28 fractions (15 of 154 patients). No grade 4 or grade 5 OT or late toxicities were reported. Rates of grade 3 acute gastrointestinal toxicity were significantly lower in patients who received EDR compared with SDR (1% vs 14%; P < .001). Similarly, rates of grade 3 OT were also lower for EDR compared with SDR (4% vs 16%; P = .004). The proportion of patients who experienced no AT was higher in the EDR group than the SDR group (36% vs 15%; P = .001). For EDR patients treated with IMRT, a lower risk of AT was associated with a later treatment year (P = .007), nonpancreatic head tumor location (P = .01), breath-hold (P = .002), 4-dimensional computed tomography (P = .003), computed tomography on rails (P = .002), and lower stomach V40 (P = .03). With a median time of 12 months (range, 1-79 months) from the start of radiation therapy to the last known follow-up in the EDR group, 51 of 59 patients (86%) had no late toxicity. Six of 59 EDR patients (10%) had either strictures or gastrointestinal bleeding that required intervention. No significant predictors of late toxicity were identified.ConclusionOverall acute and late toxicity rates were low with EDR using an IMRT technique with image guidance and respiratory gating.

Dose escalation of radiotherapy in unresectable extrahepatic cholangiocarcinoma

“…This is consistent with other studies which demonstrated that IMRT use spares normal tissue and is associated with lower GI toxicities in upper abdominal malignancies. [29][30][31][32] The use of IMRT technique did not compromise local control. Tumor size and distance from nearest GI mucosa were not taken into consideration while analyzing the protective role of IMRT.…”

Dose Escalation for Locally Advanced Pancreatic Cancer: How High Can We Go?

“…Although the LAP-07 trial 3 failed to show an overall survival benefit to radiation at standard doses, it did show benefits in terms of local control and time off of chemotherapy. At higher radiation doses, however, our institutional data suggests improved overall survival (17.8 months vs 15 months) 4 and recurrence-free survival (10.2 months vs 6.2 months), in addition to decreased acute grade 3+ gastrointestinal toxicity (1% vs 14%) 5 even at higher doses (BED>70Gy) with advanced radiation delivery techniques including use of 4-dimensional computed tomography, breath-hold technique, and image-guided radiation therapy.…”

Current and emerging radiotherapy strategies for pancreatic adenocarcinoma: stereotactic, intensity modulated and particle radiotherapy

“…Only 1 out of 200 patients in the cohort developed Grade 3 acute toxicity. In a follow-up comparative study of treatment-related toxicities in patients who had a dose escalated regimen (biological equivalent dose >70 Gy) using IMRT and those who had standard radiation dose of 50.4 Gy in 28 fractions delivered using 3D-CRT, the group observed an overall lower rates of Grade 3 acute in those who received dose-escalated regimen delivered using IMRT compared those who received standard radiation dose delivered using 3D-CRT technique (4% vs. 16%, P=0.004) (21). Six of 59 patients who received the dose-escalated regimen developed Grade 3+ late toxicity in form of either gastrointestinal stricture or bleeding.…”

“…A retrospective study by Colbert et al . (21) showed that patients who had IMRT to a higher dose (escalated dose fractionation) had lower rates of Grade 3+ acute toxicities during radiotherapy, compared to those who had 3D-CRT with conventional dose fractionation of 50.4 Gy in 28 fractions.…”