An observational multi-institutional study has been conducted aimed to evaluate the inter-observer variability in clinical target volume (CTV) delineation among different radiation oncologists in radiotherapy treatment of pancreatic cancer. A multi-institutional contouring dummy-run of two different cases of pancreatic cancer treated by postoperative and preoperative radiotherapy (RT) was performed. Clinical history, diagnostics, and planning CT imaging were available on AIRO website ( http://www.radioterapiaitalia.it ). Participants were requested to delineate CTVs according to their skills and knowledge. Aiming to quantify interobserver variability of CTVs delineations, the total volume, craniocaudal, laterolateral, and anteroposterior diameters were calculated. Descriptive statistic was calculated. The 95% Confidence Interval (95% CI) for coefficient of variation (CV) was estimated. The Dice Similarity Index (DSI) was used to evaluate the spatial overlap accuracy of the different CTVs compared with the CTVs of a national reference Centre considered as a benchmark. The mean DSI (mDSI) was calculated and reported. A total of 18 radiation oncologists from different Institutes submitted the targets. Less variability was observed for the Elective CTV rather than the Boost CTV, in both cases. The estimated CV were 28.8% (95% CI: 21.2 - 45.0%) and 20.0% (95% CI: 14.9 - 30.6%) for the Elective CTV, in adjuvant (Case 1) and neoadjuvant (Case 2) case, respectively. The mDSI value was 0.68 for the Elective CTVs in both cases (range 0.19 - 0.79 in postoperative vs range 0.35 - 0.79 in preoperative case). The mDSI was increased to 0.71 (Case 1) and 0.72 (Case 2) if the observers with a worse agreement have been excluded. On the other hand, a CV of 42.4% (95% CI: 30.1 - 72.4%) and 63.8% (95% CI: 43.9 - 119.2%) with a mDSI value of 0.44 and 0.52, were calculated for the Boost CTV in Case 1 and Case 2, respectively. The CV and mDSI obtained values for Elective CTVs showed an acceptable agreement among participants either in postoperative as well in preoperative setting. Additional strategies to reduce the variability in Boost CTV delineation need to be found and promoted.

To retrospectively evaluate the difference in terms of pathologic complete response (pCR) according to time elapsed between chemoradiation (CRT) and total mesorectal excision (TME) on a large unselected real-life dataset of locally advanced rectal cancer (LARC) patients. A multicentre retrospective cohort study of LARC patients from 21 Italian Radiotherapy Institutions was performed. Patients were stratified into 3 different time intervals from CRT. The 1st group included 300 patients who underwent TME within 6 weeks, the 2nd 1598 patients (TME within 7-12 weeks) and the 3rd 196 patients (TME within 13 or more weeks after CRT), respectively. Data on 2094 LARC patients treated between 1997 and 2016 were considered suitable for analysis. Overall, 578 patients had stage II while 1516 had stage III histological proven invasive rectal adenocarcinoma. A CRT schedule of one agent (N = 1585) or 2-drugs (N = 509) was administered. Overall, pCR was 22.3% (N = 468 patients). The proportion of patients achieving pCR with respect to time interval was, as follows: 12.6% (1st group), 23% (2nd group) and 31.1% (3rd group) (p < 0.001), respectively. The pCR relative risk comparison of 2nd to 1st group was 1.8, while 3rd to 2nd group was 1.3. Moreover, between the 3rd and 1st group, a pCR relative risk of 2.4 (p < 0.01) was noted. At univariate analysis, clinical stage III (p < 0.001), radiotherapy dose >5040 cGy (p = 0.002) and longer interval (p < 0.001) were significantly correlated to pCR. The positive impact of interval (p < 0.001) was confirmed at multivariate analysis as the only correlated factor. We confirmed on a population-level that lengthening the interval (>13 weeks) from CRT to surgery improves the pathological response (pCR and pathologic partial response; pPR) in comparison to historic data. Furthermore, radiotherapy dose >5040 cGy and two drugs chemotherapy correlated with pPR rate.

Pancreatic cancer represents a modern oncological urgency. Its management is aimed to both distal and local disease control. Resectability is the cornerstone of treatment aim. It influences the clinical presentation’s definitions as up-front resectable, borderline resectable and locally advanced (unresectable). The main treatment categories are neoadjuvant (preoperative), definitive and adjuvant (postoperative). This review will focus on (i) the current indications by the available national and international guidelines; (ii) the current standard indications for target volume delineation in radiotherapy (RT); (iii) the emerging modern technologies (including particle therapy and Magnetic Resonance [MR]-guided-RT); (iv) stereotactic body radiotherapy (SBRT), as the most promising technical delivery application of RT in this framework; (v) a particularly promising dose delivery technique called simultaneous integrated boost (SIB); and (vi) a multimodal integration opportunity: the combination of RT with immunotherapy.