Study of a Geometric Score to Identify the Increased Risk of Local Failure after SBRT for Locally Advanced Pancreatic Cancer (LAPC)

Abstract

A previous analysis on an institutional cohort of LAPC patients, treated with intensive induction chemotherapy followed by SBRT, proved that local failures (LFs) predominantly occurred within the RT field. This suggests a specific efficacy of a complete covering of the macroscopic (GTV) aggressive disease with high doses (i.e., simultaneous boost [SIB] doses). Still, this is often not feasible due to the proximity of extremely radiosensitive organs at risk (OARs), which forces the use of "Simultaneous Integrated Protection" (SIP), limiting the dose to safe values in a portion of the GTV. This analysis aimed to quantitatively assess the role of GTV size and incomplete GTV covering with SIB in increasing the risk of LF. We included 51 consecutive LAPC pts treated with SBRT (Nov 2016 - Nov 2019): 30 Gy in 5 fractions to the tumor PTV, 50 Gy SIB to the region of vessel abutment/encasement, 25 Gy SIP to the overlap between tumor PTV, and the Planning OAR volumes. We used univariate/multivariable survival analysis (UVA/MVA, Cox regression, Kaplan-Meier Curves, Log-Rank test) to assess the association of LF with the GTV size and the amount of the GTV which the SIB did not cover. Specifically, we defined a set of incomplete GTV-covering levels: GTV75 (= yes if less than 75% of the GTV was included in the 50 Gy SIB isodose), GTV70, GTV50 and GTV30. Variables with p≤0.2 at UVA were included for MVA assessment. MVA models were considered relevant if their likelihood was significantly higher when compared to UVA. With a median follow-up of 17 months (range 1.4-47) 12 pts experienced LF. The GTV size (p = 0.007, risk factor for LF, Hazard Ratio [HR] 1.04 for 1 cc increase in GTV size) and GTV70 (p = 0.2, risk factor, HR = 3.73 for GTV70 = yes) were selected at UVA and included in MVA. To build a simple decision tool, we dichotomized the GTV size as below/above 25 cc (selected from Youden Index on the ROC curve): HR = 9.3 if GTV>25 cc. We used dichotomized GTV size and GTV70 to build a 3-level Geometric Score for the prediction of the risk of LF: [Low Risk (LR)] if "GTV<25cc AND GTV70 = no"; [Intermediate Risk (IR)] if "GTV>25cc OR GTV70 = yes"; [High Risk (HiR)] if "GTV>25cc AND GTV70 = yes". Pts classified at HiR had a significantly higher probability of LF: HR = 6.9 (95% CI 1.5-32.9) compared to LR, and HR = 13.2 (95% CI 3.6-48.4) when compared to IR. 10/12 LFs are in the HiR group. A large GTV size, coupled with an incomplete (<70%) covering of GTV from the SIB, highly increases the risk of LF: 62% actuarial probability in the HiR group vs 7% in the LR/IR groups. Full coverage of the GTV with SIB would be of clinical relevance for pts with large macroscopic tumors. The Geometric Score could be used to select pts that would effectively benefit from online tumor tracking (e.g., with an MRI-Linac), allowing a reduction of the SIP volume and a consequent decrease in the amount of GTV left uncovered by the SIB.