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.

A multi-institutional retrospective study was conducted to evaluate the pattern of care and clinical outcomes of anal cancer patients treated with intensity-modulated radiotherapy (IMRT) techniques. In a cohort of 987 patients, the clinical complete response (CR) rate (beyond 6 months) was 90.6%. The 3-year local control (LC) rate was 85.8% (95% CI: 84.4–87.2), and the 3-year colostomy-free survival (CFS) rate was 77.9% (95% CI: 76.1–79.8). Three-year progression-free survival (PFS) and overall survival (OS) rates were 80.2% and 88.1% (95% CI: 78.8–89.4) (95% CI: 78.5–81.9), respectively. Histological grade 3 and nodal involvement were associated with lower CR (p = 0.030 and p = 0.004, respectively). A statistically significant association was found between advanced stage and nodal involvement, and LC, CFS, PFS, OS and event-free survival (EFS). Overall treatment time (OTT) ≥45 days showed a trend for a lower PFS (p = 0.050) and was significantly associated with lower EFS (p = 0.030) and histological grade 3 with a lower LC (p = 0.025). No statistically significant association was found between total dose, dose/fraction and/or boost modality and clinical outcomes. This analysis reports excellent clinical results and a mild toxicity profile, confirming IMRT techniques as standard of care for the curative treatment of anal cancer patients. Lymph node involvement and histological grade have been confirmed as the most important negative prognostic factors.

Background: Radiotherapy (RT) plays an important role in the treatment of patients with previously irradiated locally recurrent rectal cancer (LRRC). Over the years, numerous technologies and different types of RT have emerged. The aim of our systematic literature review was to determine whether the new techniques have led to improvements in both outcomes and toxicities. Methods: A computerized search was performed by MEDLINE and the Cochrane database. The studies reported data from patients treated with carbon ion radiotherapy (CIRT), intensity-modulated photon radiotherapy (IMRT), and stereotactic radiotherapy (SBRT). Results: Seven publications of the 126 titles/abstracts that emerged from our search met the inclusion criteria and presented outcomes of 230 patients. OS was reported with rates of 90.0% and 73.0% at 1 and 2 years, respectively; LC was 89.0% and 71.6% at 1 and 2 years after re-RT, respectively. Toxicity data vary widely, with emphasis on acute and chronic gastrointestinal and urogenital toxicity, even with modern techniques. Conclusion: data on toxicity and outcomes of re-RT for LRRC with new technologies are promising compared with 3D techniques. Comparative studies are needed to define the best technique, also in relation to the site of recurrence.

Background: Despite the feasibility and promising activity data on intensity-modulated RT and simultaneous integrated boost (IMRT-SIB) dose escalation in preoperative chemoradiation (CRT) for locally advanced rectal cancer (LARC), few data are currently available on long-term outcomes. Patients and Methods: A cohort of 288 LARC patients with cT3-T4, cN0-2, cM0 treated with IMRT-SIB and capecitabine from March 2013 to December 2019, followed by a total mesorectal excision (TME) or an organ-preserving strategy, was collected from a prospective database of 10 Italian institutions. A dose of 45 Gy in 25 fractions was prescribed to the tumor and elective nodes, while the SIB dose was prescribed according to the clinical practice of each institution on the gross tumor volume (GTV). Concurrent capecitabine was administered at a dose of 825 mg/m² twice daily, 7 days a week. The primary objective of the study was to evaluate long-term outcomes in terms of local control (LC), progression-free survival (PFS) and overall survival (OS). The secondary objective was to confirm the previously reported feasibility, safety and efficacy (pCR, TRG1-2 and downstaging rates) of the treatment in a larger patient population. Results: All patients received a dose of 45 Gy to the tumor and elective nodes, while the SIB dose ranged from 52.5 Gy to 57.5 Gy (median 55 Gy). Acute gastrointestinal and hematologic toxicity rates of grade 3–4 were 5.7% and 1.8%, respectively. At preoperative restaging, 36 patients (12.5%) with complete or major clinical responses (cCR or mCR) were offered an organ-preserving approach with local excision (29 patients) or a watch and wait strategy (7 patients). The complete pathologic response rate (pCR) in radically operated patients was 25.8%. In addition, 4 TME patients had pT0N1 and 19 LE patients had pT0Nx, corresponding to an overall pT0 rate of 31.3%. Of the 36 patients selected for organ preservation, 7 (19.5%) required the completion of TME due to unfavorable pathologic features after LE or tumor regrowth during W-W resulting in long-term rectal preservation in 29 of 288 (10.1%) of the total patient population. Major postoperative complications occurred in 14.2% of all operated patients. At a median follow-up of 50 months, the 5-year PFS and OS rates were 72.3% (95% CI: 66.3–77.4) and 85.9% (95% CI: 80.2–90.1), respectively. The 5-year local recurrence (LR) rate was 9.2% (95% CI: 6.0–13.2), while the distant metastasis (DM) rate was 21.3% (95% CI: 16.5–26.5). The DM rate was 24.5% in the high-risk subset compared to 16.2% in the low-intermediate risk group (p = 0.062) with similar LR rates (10% and 8%, respectively). On multivariable analysis, cT4 and TRG3–5 were significantly associated with worse PFS, OS and metastasis-free survival. Conclusions: Preoperative IMRT-SIB with the moderate dose intensification of 52.5–57.5 Gy (median 55 Gy) and the full dose of concurrent capecitabine confirmed to be feasible and effective in our real-life clinical practice. Organ preservation was shown to be feasible in carefully selected, responsive patients. The favorable long-term survival rates highlight the efficacy of this intensified treatment program. The incorporation of IMRT-SIB with a more effective systemic therapy component in high-risk patients could represent a new area of investigational interest.