Dosimetric parameters correlate with duodenal histopathologic damage after stereotactic body radiotherapy for pancreatic cancer: Secondary analysis of a prospective clinical trial

Abstract

Purpose Prospectively assess relationships between dosimetric parameters and histopathologic/clinical duodenal toxicities in patients on a phase I trial for pancreatic cancer. Methods Forty-six borderline resectable/unresectable patients were enrolled on a prospective trial testing neoadjuvant gemcitabine/5-fluorouracil followed by SBRT (5 daily fractions of 5–8 Gy) and concurrent nelfinavir. Post-SBRT surgery was performed in 13 resectable patients, which constituted the patient population herein. Pathologic duodenal damage was assessed using predetermined criteria: 1, no/minimal; 2, moderate; and 3, marked damage. Clinical toxicities were assessed per CTCAE. Duodenal dosimetric parameters included V5–V40 and mean/maximum doses. Spearman correlation and linear regression evaluated associations between dosimetric parameters and clinical/pathologic duodenal toxicity. Results The median duodenal mean and maximum doses were 20 and 37 Gy. Median duodenal V5–V40 were 64, 62, 52, 39, 27, 14, 5 and 0 cc, respectively. The median duodenal damage score was 2 (four 1, eight 2, and one 3). Higher duodenal damage scores correlated with higher duodenal mean doses (r = 0.75, p = 0.003), V35 (r = 0.61, p = 0.03), V30 (r =0.67, p = 0.01), V25 (r =0.68, p = 0.01), V20 (r = 0.56, p = 0.05), and the planning target volume (PTV) mean (r =0.59, p = 0.03) and maximum (r = 0.61, p = 0.03) doses. Clinical toxicities did not correlate with dosimetric parameters or duodenal pathologic damage. Conclusions Duodenal histologic damage correlates with mean duodenal dose, V20–V35, and PTV mean/−maximum doses.

Biological determinants of radioresistance and their remediation in pancreatic cancer

“…Our study showed that duodenal histologic damage correlates with mean duodenal dose, V20–V35, and PTV mean/maximum doses [328]. As the use of high-dose SBRT regimens becomes widespread, it is imperative to explore modalities that can selectively radioprotect adjacent organs without altering the tumor response.…”

Feasibility and reproducibility of substituting oral contrast with water for duodenal volume delineation in patients undergoing pancreatic stereotactic body radiotherapy

“…Our study showed that duodenal histologic damage but not the clinical toxicities correlate with the mean duodenal dose, V20-V35, and the PTV mean/maximum doses. In this cohort, four grade-2 and one grade-3 acute toxicities were observed (18).…”

Dose-escalated radiotherapy for unresectable or locally recurrent pancreatic cancer: Dose volume analysis, toxicity and outcome of 28 consecutive patients

“…Published data on OAR constraints and toxicity show a large heterogeneity. For pancreatic cancer Kelly described a correlation of V 55Gy within the duodenum and gastro-intestinal toxicity [23], however in a small cohort of patients treated with hypofractionated stereotactic RT duodenal DVHs only correlated to histomorphological alterations but not to clinical scored toxicity [24]. The best available data on small intestine constraints from QUANTEC recommends that the dose to the small bowel receiving ≥ 45 Gy should not exceed 200 ml, if the entire peritoneal space is delineated.…”