Material and Methods
Two KBP models were created, at the Tata Memorial Centre – India (Rapid plan v13.5.23, Varian Medical Systems) and Aarhus University Hospital – Denmark (Rapidplan, v16.1)using patients treated at their respective departments and was validated through comparison with the manually optimised clinical plans. Clinical plans were created by expert dose planners who had undergone accreditation according to EMBRACE II quality criteria. The KBP model was developed using training (n=125) based on clinical treatment plans based on dose constraints of the EMBRACE-II protocol. For this analysis, the KBP models were shared between the two centres and prospective planning was performed. Validation was carried out in a total of 20 patient data sets: 10 node positive (N+) and negative (N-) at each institution. Three plans for each data set, clinical plan, Tata KBP, and Aarhus KBP, were created, thereby generating a total of 120 plans. Plans based on KBP were generated in a single run optimization without any manual intervention. Quantitative comparison of dosimetric indices was performed between clinical vs. Tata KBP, Clinical vs. Aarhus KBP and Tata KBP vs. Aarhus KBP, using Wilcoxon sign rank sum test. p value <0.05 was considered statistically significant.
Results
Both models have excellent compliance to the protocol specific dose constraints. Between the two KBP, Aarhus model resulted in high conformity for N+ Tata patients (CI43Gy 1.0 vs 1.09 p=0.0051, CI36Gy 1.6 vs 1.4 p=0.0051), improved OAR sparing, while under-dosing targets marginally, whereas Tata models resulted in comparable plans for Aarhus patients, both in terms of OAR sparing and conformality, however, marginal overdose of target coverage was observed. The details are as follows:
For Tata N- patients, Aarhus model resulted in significant bowel (V40Gy p= 0.009, V30Gy = 0.005, V15Gy =0.005), bladder (V40Gy = 0.007, V30Gy = 0.006) and rectum sparing (V40Gy = 0.006), while under dosing the target marginally i.e. PTV45 (V42.75Gy 96.8±1.1 vs 94±1 p=0.005, CTV-N D98 55.4±0.2 vs 54.5±0.5 p=0.0051) as compared to Tata model (Table 1). This under-dose in target coverage may overcome with plan normalization.
For Aarhus N- patients, Tata model resulted in comparable plans both for target coverage (PTV45V42.75Gy 96.1±0.7 vs. 97.2±1.2 p=0.96, CTV-N D98 55.9±1.5 vs 55.8±0.1 p=0.07) and OAR sparing (bowel V40Gy , V30Gy, V15Gy, bladder V40Gy , V30Gy and rectum V40Gy, V30Gy p>0.36) as compared to Aarhus clinical plans.. For N+ patients, Tata model resulted in comparable target coverage, with marginally less OAR sparing (bowel V40Gy p= 0.01, V30Gy = 0.007, V15Gy =0.44, bladder V40Gy and V30Gy = 0.028 and rectum V40Gy = 0.025, V30Gy = 0.48). Tata model resulted in good conformality in N- patients (CI V43 0.99 vs 1.00 p = 0.2, V36 1.46 vs 1.42 p=0.02), however for N+ patients, it was marginally less (CI V43 1.04 vs 1.075 p = 0.0051, V36 1.53 vs 1.6 p=0.0051) as compared to clinical plans.
Conclusion
Protocol compliance was good in both clinical and KBP plans, across the institutions. Geo-ethnic validation of these KBP models suggests that with appropriate training, KBP models result in plans with similar quality as compared to clinical plans carried out by expert dose planners. Given that unexperienced dose planners may produce plans of less quality than experienced planners, KBP has potential to improve quality and trial specific protocol compliance.