Conformity analysis to demonstrate reproducibility of target volumes for Margin-Intense Stereotactic Radiotherapy for borderline-resectable pancreatic cancer.

Margin-directed neoadjuvant radiotherapy for borderline-resectable pancreatic cancer (BRPC) aims to facilitate clear surgical margins. A systematic method was developed for definition of a boost target volume prior to a formal phase-I study.Reference structures were defined by two oncologists and one radiologist, target structures were submitted by eight oncologist investigators and compared using conformity indices. Resultant risk of duodenal bleed (NTCP) was modelled.For GTV, reference volume was 2.1cm(3) and investigator mean was 6.03cm(3) (95% CI 3.92-8.13cm(3)), for boost volume 1.1cm(3) and 1.25cm(3) (1.02-1.48cm(3)). Mean Dice conformity coefficient for GTV was 0.47 (0.38-0.56), and for boost volume was significantly higher at 0.61 (0.52-0.70, p=0.01). Discordance index (DI) for GTV was 0.65 (0.56-0.75) and for boost volume was significantly lower at 0.39 (0.28-0.49, p=0.001). NTCP using reference contours was 2.95%, with mean for investigator contour plans 3.93% (3.63-4.22%). Correlations were seen between NTCP and GTV volume (p=0.02) and NTCP and DI (correlation coefficient 0.83 (0.29-0.97), p=0.01).Better conformity with reference was shown for boost volume compared with GTV. Investigator GTV volumes were larger than reference, had higher DI scores and modelled toxicity risk. A consistent method of target structure definition for margin-directed pancreatic radiotherapy is demonstrated

Superior outcomes of nodal metastases compared to visceral sites in oligometastatic colorectal cancer treated with stereotactic ablative radiotherapy

Background: Stereotactic ablative radiotherapy (SBRT) is a radical option for oligometastatic colorectal cancer (CRC) patients, but most data relate to visceral metastases. Methods: A prospective, multi-centre database of CRC patients treated with SBRT was interrogated. Inclusion criteria were ECOG PS 0–2, ≤3 sites of disease, a disease free interval of >6 months unless synchronous liver metastases. Primary endpoints were local control (LC), progression free survival (PFS) and overall survival (OS). Results: 163 patients (172 metastases) were analysed. The median FU was 16 months (IQR 12.2–22.85). The LC at 1 year was 83.8% (CI 76.4%−91.9%) with a PFS of 55% (CI 47%−64.7%) respectively. LC at 1 year was 90% (CI 83%−99%) for nodal metastases (NM), 75% (63%−90%) for visceral metastases (VM). NM had improved median PFS (9 vs 19 months) [HR 0.6, CI 0.38–0.94, p = 0.032] and median OS (32 months vs not reached) [HR 0.28, CI 0.18–0.7, p = 0.0062] than VM, regardless of whether the NM were located inside or outside the pelvis. On multivariate analysis, NM and ECOG PS 0 were significant good prognostic factors. An exploratory analysis suggests KRAS WT is also a good prognostic factor. Conclusion: Nodal site is an important prognostic determinant of SBRT that should incorporated into patient selection. We hypothesise this may have an immunoediting basis

Modelling duodenum radiotherapy toxicity using cohort dose-volume-histogram data

Background and purpose Gastro-intestinal toxicity is dose-limiting in abdominal radiotherapy and correlated with duodenum dose-volume parameters. We aimed to derive updated NTCP model parameters using published data and prospective radiotherapy quality-assured cohort data. Material and methods A systematic search identified publications providing duodenum dose-volume histogram (DVH) statistics for clinical studies of conventionally-fractionated radiotherapy. Values for the Lyman-Kutcher-Burman (LKB) NTCP model were derived through sum-squared-error minimisation and using leave-one-out cross-validation. Data were corrected for fraction size and weighted according to patient numbers, and the model refined using individual patient DVH data for two further cohorts from prospective clinical trials. Results Six studies with published DVH data were utilised, and with individual patient data included outcomes for 531 patients in total (median follow-up 16 months). Observed gastro-intestinal toxicity rates ranged from 0% to 14% (median 8%). LKB parameter values for unconstrained fit to published data were: n = 0.070, m = 0.46, TD50(1) [Gy] = 183.8, while the values for the model incorporating the individual patient data were n = 0.193, m = 0.51, TD50(1) [Gy] = 299.1. Conclusions LKB parameters derived using published data are shown to be consistent to those previously obtained using individual patient data, supporting a small volume-effect and dependence on exposure to high threshold dose