Dose escalation for locally advanced pancreatic cancer: How high can we go?

Abstract

PurposeThere are limited treatment options for locally advanced, unresectable pancreatic cancer (LAPC) and no likelihood of cure without surgery. Radiation offers an option for local control, but radiation dose has previously been limited by nearby bowel toxicity. Advances in on-board imaging and treatment planning may allow for dose escalation not previously feasible and improve local control. In preparation for development of clinical trials of dose escalation in LAPC, we undertook a dosimetric study to determine the maximum possible dose escalation while maintaining known normal tissue constraints.Methods and MaterialsTwenty patients treated at our institution with either SBRT or dose-escalated hypofractionated IMRT (DE-IMRT) were re-planned using dose escalated SBRT to 70 Gy in 5 fractions to the GTV and 40 Gy in 5 fractions to the PTV. Standard accepted organ at risk (OAR) constraints were used for planning. Descriptive statistics were generated for homogeneity, conformality, OAR's and GTV/PTV.ResultsMean iGTV coverage by 50 Gy was 91% (±0.07%), by 60 Gy was 61.3% (±0.08%) and by 70 Gy was 24.4% (±0.05%). Maximum PTV coverage by 70 Gy was 33%. Maximum PTV coverage by 60 Gy was 77.5%. The following organ at risk (OAR) constraints were achieved for 90% of generated plans: Duodenum V20 < 30 cc, V30 < 3 cc, V35 < 1 cc; Small Bowel V20 < 15 cc, V30 < 1 cc, V35 < 0.1 cc; Stomach V20 < 20 cc, V30 < 2 cc, V35 < 1 cc. V40 < 0.5 cc was achieved for all OAR.ConclusionsDose escalation to 60 Gy is dosimetrically feasible with adequate GTV coverage. The identified constraints for OAR's will be used in ongoing clinical trials.

Dosimetric Feasibility Study of Dose Escalated Stereotactic Body Radiation Therapy (SBRT) in Locally Advanced Pancreatic Cancer (LAPC) Patients: It Is Time to Raise the Bar

“…Based on these results, we evaluated the opportunity and feasibility of a dose escalation protocol, with the aim of improving the clinical outcomes of the aforementioned SBRT approach. In this regard, a recent MDACC study provided a remarkable roadmap to achieve a dose escalation up to 60 Gy in SBRT for LAPC (17). The currently recommended dose in pancreatic SBRT is 33-40 Gy in five fractions (BED 10 = 54.78-72 Gy) (18), instead BED 10 of not less than 100 Gy is generally advocated to maximize the RT therapeutic effect and improve oncological outcomes (19).…”

“…Based on these results, we evaluated the opportunity and feasibility of a dose escalation protocol, with the aim of improving the clinical outcomes of the aforementioned SBRT approach. In this regard, a recent MDACC study provided a remarkable roadmap to achieve a dose escalation up to 60 Gy in SBRT for LAPC ( 17 ).…”

Comparison of the dose escalation potential for two hypofractionated radiotherapy regimens for locally advanced pancreatic cancer

“…The benefit of a high BED for local control in LAPC has been previously demonstrated in tumours smaller than 5 cm and/or more than 0.5 cm away from GI OAR [7], [12], [15], [23]. However, dose escalation is challenging when the anatomy is less favourable, especially using a 5 fraction SBRT approach.…”

Rationale for Involved Field Stereotactic Body Radiation Therapy-Enhanced Intermittent Androgen Deprivation Therapy in Hormone-Sensitive Nodal Oligo-Recurrent Prostate Cancer Following Prostate Stereotactic Body Radiation Therapy

“…Therefore, we recommend a very conservative constraint of 30 Gy <1 cc to the bowel, a constraint for which the risk of significant toxicity is very low (5%) ( 63 ). Moderate doses to larger portions of bowel may also impact the risk of toxicity so we recommend the volume of bowel receiving 20 Gy <15 cc ( 64 ). (Please see Table 1 for additional proposed dose constraints).…”