The multimodal approach with total mesorectal excision preceded by neoadjuvant (chemo)radiotherapy represented the mainstay treatment for locally advanced rectal cancer (LARC) for a long time. However, the benefit of adjuvant chemotherapy in terms of distant relapse reduction is limited. Recently, chemotherapy regimens administered before surgery and incorporated with (chemo)radiotherapy in total neoadjuvant treatment protocols have been established as new options in the management of LARC. Meanwhile, patients with clinical complete response to neoadjuvant treatment can benefit from organ preservation strategies, aimed at sparing surgery and long-term post-operative morbidities, while preserving an adequate disease control. However, the introduction of a non-operative management in clinical practice is a matter of debate with some concerns regarding the risk of local recurrence and long-term outcomes. In this review, we discuss how these recent advances are reshaping the multimodal management of localized rectal cancer and propose an algorithm to place them in the clinical practice.

Background: In patients with locally advanced rectal cancer (LARC) treated with preoperative (chemo) radiotherapy and surgery, adjuvant chemotherapy is poorly feasible and its benefit is questionable. In the last years, several total neoadjuvant treatment (TNT) strategies, moving the adjuvant chemotherapy to the neoadjuvant setting, have been investigated with the aim of improving compliance to systemic chemotherapy, treating micrometastases earlier and then reducing distant recurrence. Patients and Methods: ShorTrip (NTC05253846) is a prospective, multicentre, singlearm phase II trial where 63 patients with LARC will be treated with short-course radiotherapy followed by intensified consolidation chemotherapy with FOLFOXIRI regimen and surgery. Primar y endpoint is pCR. Among the first 11 patients who started consolidation chemotherapy, a preliminary safety analysis showed a high rate of grade 3 to 4 neutropenia (N = 7, 64%) during the first cycle of FOLFOXIRI. Therefore, the protocol has been emended with the recommendation to omit irinotecan during the first cycle of consolidation chemotherapy. After amendment, in a subsequent safety analysis focused on the first 9 patients treated with FOLFOX as first cycle and then with FOLFOXIRI, grade 3 to 4 neutropenia was reported in only one case during the second cycle.Aim of the study: The aim of this study is to assess the safety and activity of a TNT strategy including SCRT, intensified consolidation treatment with FOLFOXIRI and delayed surgery. After protocol amendment, the treatment seems feasible without safety concern. Results are expected at the end of 2024.

The purpose of this study was to investigate the effect of image preprocessing on radiomic features estimation from computed tomography (CT) imaging of locally advanced rectal cancer (LARC). CT images of 20 patients with LARC were used to estimate 105 radiomic features of 7 classes (shape, first-order, GLCM, GLDM, GLRLM, GLSZM, and NGTDM). Radiomic features were estimated for 6 different isotropic resampling voxel sizes, using 10 interpolation algorithms (at fixed bin width) and 6 different bin widths (at fixed interpolation algorithm). The intraclass correlation coefficient (ICC) and the coefficient of variation (CV) were calculated to assess the variability in radiomic features estimation due to preprocessing. A repeated measures correlation analysis was performed to assess any linear correlation between radiomic feature estimate and resampling voxel size or bin width. Reproducibility of radiomic feature estimate, when assessed through ICC analysis, was nominally excellent (ICC > 0.9) for shape features, good (0.75 < ICC ≤ 0.9) or moderate (0.5 < ICC ≤ 0.75) for first-order features, and moderate or poor (0 ≤ ICC ≤ 0.5) for textural features. A number of radiomic features characterized by good or excellent reproducibility in terms of ICC showed however median CV values greater than 15%. For most textural features, a significant (p < 0.05) correlation between their estimate and resampling voxel size or bin width was found. In CT imaging of patients with LARC, the estimate of textural features, as well as of first-order features to a lesser extent, is appreciably biased by preprocessing. Accordingly, this should be taken into account when planning clinical or research studies, as well as when comparing results from different studies and performing multicenter studies.

BACKGROUND/AIM:A much-debated topic relating to patients at risk of local prostate cancer recurrence, but with post-operative leveIs of prostate-specific antigen (PSA) lower than 0.2 ng/ml, concerns the best timing of postoperative radiotherapy (RT), adjuvant or salvage? The present monocentric, retrospective study aimed to investigate the best PSA value at which to plan salvage RT for patients with recurrent prostate cancer.PATIENTS AND METHODS:From January 2011 to December 2019, 158 patients were treated with adjuvant RT at Pisa University Hospital, whilst 91 patients underwent salvage RT. We grouped the patients treated with salvage RT using their PSA values at the time of salvage RT: PSA >0.5 ng/ml, PSA between 0 and 0.5 ng/ml, and PSA ≤0.2 ng/ml. The median follow-up was 63 months. Biochemical recurrence-free survival (BFS) measured from surgery was the primary endpoint.RESULTS:Salvage RT led to shorter BFS compared to adjuvant RT considering the whole cohort of patients, with a hazard ratio of 3.195 (95% confidence interval=1.534-6.655, p=0.002). However, analysing only the group of patients with PSA ≤0.2 ng/ml at the time of salvage RT, salvage RT led to BFS similar to that achieved with adjuvant RT (p=0.35).CONCLUSION:Our results suggest that when scheduled for patients with a PSA ≤0.2 ng/ml, salvage RT results in equivalent biochemical control to that with adjuvant RT.

Background and Purpose: Tumor recurrence, a characteristic of malignant tumors, is the biggest concern for rectal cancer survivors. The epidemiology of the disease calls for a pressing need to improve healthcare quality and patient outcomes. Prediction models such as Bayesian networks, which can probabilistically reason under uncertainty, could assist caregivers with patient management. However, some concerns are associated with the standard approaches to developing these structures in medicine. Therefore, this study aims to compare Bayesian network structures that stem from these two techniques.Materials and Methods: A retrospective analysis was performed on 6754 locally advanced rectal cancer (LARC) patients enrolled in 14 international clinical trials. Local tumor recurrence at 2, 3, and 5-years was defined as the endpoints of interest. Five rectal cancer treating physicians from three countries elicited the expert structure. The algorithmic structure was inferred from the data with the hill-climbing algorithm. Structural performance was assessed with calibration plots and area under the curve values.Results: The area under the curve for the expert structure on the training and validation data was above 0.9 and 0.8, respectively, for all the time points. However, the algorithmic structure had superior predictive performance over the expert structure for all time points of interest.Conclusion: We have developed and internally validated a Bayesian networks structure from experts' opinions, which can predict the risk of a LARC patient developing a tumor recurrence at 2, 3, and 5 years. Our result shows that the algorithmic-based structures are more performant and less interpretable than expert based structures.

AIM:Pancreatic adenocarcinoma is a life-threatening disease with a rising frequency and the fourth leading cause of cancer death. This review aimed to assess the impact of postoperative radiotherapy through a meta-analysis of prospective randomized studies.MATERIALS AND METHODS:Six studies met the inclusion criteria and were analyzed to calculate the cumulative risk of death (hazard ratio) in patients affected by pancreatic cancer treated with or without radiotherapy. Higgins' index was used to determine heterogeneity in between-study variability and, subsequently, the random-effects model was applied according to DerSimonian and Laird.RESULTS:Eight hundred and thirty-seven patients were analyzed (418 in the control arm and 419 in the treatment one), the hazard ratio for death after randomization was 0.92 (p=0.560, 95% confidence interval=0.70-1.22). When scrutinizing these studies, only one out of six showed a statistically significant benefit due to the addition of radiotherapy in the postoperative setting.CONCLUSION:We conclude that the use of adjuvant radiotherapy is not beneficial in treating all patients affected by pancreatic cancer but only for a subset of cases with potential residual local disease.

The study aimed to generate a local failure (LF) risk map in resected pancreatic cancer (PC) and validate the results of previous studies, proposing new guidelines for PC postoperative radiotherapy clinical target volume (CTV) delineation. Follow-up computer tomography (CT) of resected PC was retrospectively reviewed by two radiologists identifying LFs and plotting them on a representative patient CT scan. The percentages of LF points randomly extracted based on CTV following the RTOG guidelines and based on the LF database were 70% and 30%, respectively. According to the Kernel density estimation, an LF 3D distribution map was generated and compared with the results of previous studies using a Dice index. Among the 64 resected patients, 59.4% underwent adjuvant treatment. LFs closer to the root of the celiac axis (CA) or the superior mesenteric artery (SMA) were reported in 32.8% and 67.2% cases, respectively. The mean (± standard deviation) distances of LF points to CA and SMA were 21.5 ± 17.9 mm and 21.6 ± 12.1 mm, respectively. The Dice values comparing our iso-level risk maps corresponding to 80% and 90% of the LF probabilistic density and the CTVs-80 and CTVs-90 of previous publications were 0.45–0.53 and 0.58–0.60, respectively. According to the Kernel density approach, a validated LF map was proposed, modeling a new adjuvant CTV based on a PC pattern of failure.

Background In the last years, functional imaging has given a significant contribution to the clinical decision-making of biochemically relapsed prostate cancer (PCa). Hereby, we present a prospective study aiming to validate the role of [ 18 F]Fluoro-Methyl Choline ([ 18 F]FMCH) PET/CT in the selection of PCa patients suitable for stereotactic body radiotherapy (SBRT). Methods Patients with biochemical recurrence limited up to three lesions revealed by [ 18 F]FMCH PET/CT were enrolled in the present study and treated with SBRT on all active lesions. Systemic therapy-free survival since the [ 18 F]FMCH PET/CT was considered as the primary endpoint. Results Forty-six patients were evaluated, and a total of 67 lesions were treated. After a median follow-up of 28.9 months, systemic therapy was started in 30 patients (65.2%) and median systemic therapy-free survival was 39.1 months (95% CI 6.5–68.6); 6, 12, and 24-month ratios were 93.5%, 73.9%, and 63.1%, respectively. At univariate Cox regression analysis, Delta PSA demonstrated an impact on systemic therapy-free survival ( p < 0.001). Conclusions Based on our findings, [ 18 F]FMCH PET/CT can identify oligometastatic prostate cancer patients suitable for SBRT, resulting in a systemic therapy-free survival of 39.1 months.

Background: Due to the high soft tissue resolution, magnetic resonance imaging (MRI) could improve the accuracy of pancreatic tumor delineation in radiation treatment planning. A multi-institutional study was proposed to evaluate the impact of MRI on inter-observer agreement in gross tumor volume (GTV) and duodenum delineation for pancreatic cancer compared with computer tomography (CT). Material and Methods: Two clinical cases of borderline resectable (Case 1) and unresectable (Case 2) pancreatic cancer were selected. In two sequential steps, diagnostic contrast-enhanced CT scan and MRI sequences were sent to the participating centers. CT-GTVs were contoured while blinded to MRI data sets. DICE index was used to evaluate the spatial overlap accuracy. Results: Thirty-one radiation oncologists from different Institutions submitted the delineated volumes. CT- and MRI-GTV mean volumes were 21.6 +/- 9.0 cm(3) and 17.2 +/- 6.0 cm(3), respectively for Case 1, and 31.3 +/- 15.6 cm(3) and 33.2 +/- 20.2 cm(3), respectively for Case 2. Resulting MRI-GTV mean volume was significantly smaller than CT-GTV in the borderline resectable case (p < .05). A substantial agreement was shown by the median DICE index for CT- and MRI-GTV resulting as 0.74 (IQR: 0.67-0.75) and 0.61 (IQR: 0.57-0.67) for Case 1; a moderate agreement was instead reported for Case 2: 0.59 (IQR:0.52-0.66) and 0.53 (IQR:0.42-0.62) for CT- and MRI-GTV, respectively. Conclusion: Diagnostic MRI resulted in smaller GTV in borderline resectable case with a substantial agreement between observers, and was comparable to CT scan in interobserver variability, in both cases. The greater variability in the unresectable case underlines the critical issues related to the outlining when vascular structures are more involved. The integration of MRI with contrast-enhancement CT, thanks to its high definition of tumor relationship with neighboring vessels, could offer a greater accuracy of target delineation.

ConclusionTumor persistence and distant recurrence were the main patterns of lack of disease control.Persistence after (chemo)radiotherapy negatively impacted survival.Outof-field was the least frequent recurrence pattern.It is acceptable to maintain IFI technique.

Background: Neoadjuvant chemoradiotherapy (CRT) in locally advanced rectal cancer (LARC) does not achieve effective control of distant metastases. Induction chemotherapy is a promising strategy, and bevacizumab (BV) could improve the results of CRT. 5-Fluorouracil, oxaliplatin and irinotecan (FOLFOXIRI) plus BV is a treatment option in metastatic colorectal cancer. We evaluate feasibility and efficacy of neoadjuvant treatment comprising induction FOLFOXIRI plus BV followed by CRT with fluoropyrimidines plus BV. Methods: In this phase II single-arm trial, patients node-positive or clinical T4 or high-risk T3 LARC underwent 6 cycles of induction FOLFOXIRI plus BV, followed by CRT (50.4 Gy plus concomitant capecitabine) and BV (5 mg/kg on days 1, 15 and 28). Surgery was planned 8 weeks after completion of CRT. Primary end-point was 2-year disease-free survival (DFS). Results: We enrolled 49 patients: All but one (withdrewing consent after enrolment) were included in the per-protocol analyses. The study met its primary end-point: 36 patients were free of recurrence at 2 years (2-y DFS: 80.45%, 95% confidence interval [ CI]: 78.79-82.10). Forty-four patients underwent surgery; pathologic complete response rate was 36.4%. Forty-six patients completed induction: neutropenia (41.6%) and diarrhoea (12.5%) were main G3/4 toxicities. Forty-five patients received CRT, but the protocol was amended and the capecitabine schedule during CRT was slightly modified after 13 patients due to the incidence of G3 hand-foot syndrome and proctitis (23.1%). After amendment, no severe events during CRT were reported. Conclusions: FOLFOXIRI plus BV followed by CRT plus BV is feasible and active. Results in terms of DFS suggest that this strategy may improve distant disease control in LARC. (C) 2019 Elsevier Ltd. All rights reserved.

S854ESTRO 37[95% CI: 1.20-6.80],p=0.018) were independent prognostic factors for worse OS. ConclusionWe found that WPRT as compared with PBRT did not significantly improve bPFS or OS.On the contrary, OS following WPRT was significantly lower than that after PBRT.Our results bring into questions whether second cancers may be increased with WPRT.

S855ESTRO 37treatment plan conformity index, pattern of metastatic disease, prostate cancer status and GS were not significantly correlated with failure of local control.Toxicity greater than G2 were not recorded. ConclusionIn patients with metastatic prostate cancer, imageguided intensity-modulated stereotactic body radiotherapy is a noninvasive procedure resulting in high local control and low toxicity profile.