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.

Different options for locally advanced pancreatic cancer (LAPC) are available based on international guidelines: chemotherapy (CHT), chemoradiation (CRT), and stereotactic body radiotherapy (SBRT). However, the role of radiotherapy is debated in LAPC. We retrospectively compared CHT, CRT, and SBRT ± CHT in a real-world setting in terms of overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS). LAPC patients from a multicentric retrospective database were included (2005–2018). Survival curves were calculated using the Kaplan–Meier method. Multivariable Cox analysis was performed to identify predictors of LC, OS, and DMFS. Of the 419 patients included, 71.1% were treated with CRT, 15.5% with CHT, and 13.4% with SBRT. Multivariable analysis showed higher LC rates for CRT (HR: 0.56, _95%CI 0.34–0.92, p = 0.022) or SBRT (HR: 0.27, _95%CI 0.13–0.54, p < 0.001), compared to CHT. CRT (HR: 0.44, _95%CI 0.28–0.70, p < 0.001) and SBRT (HR: 0.40, _95%CI 0.22–0.74, p = 0.003) were predictors of prolonged OS with respect to CHT. No significant differences were recorded in terms of DMFS. In selected patients, the addition of radiotherapy to CHT is still an option to be considered. In patients referred for radiotherapy, CRT can be replaced by SBRT considering its duration, higher LC rate, and OS rate, which are at least comparable to that of CRT.

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.

Background/Objectives: To present the technical aspects of contrast-enhanced 4DCT (ce4DCT) simulation for abdominal SBRT. Methods: Twenty-two patients underwent two sequential 4DCT scans: one baseline and one contrast-enhanced with personalized delay time (tdelay) calculated to capture the tumor in the desired contrast phase, based on diagnostic triple-phase CT. The internal target volume (ITV) was delineated on ten contrast phases, and a panel of three experts qualitatively evaluated tumor visibility. Aortic HU values were measured to refine the tdelay for subsequent patients. The commonly used approach of combining triple-phase CT with unenhanced 4DCT was simulated, and differences in target delineation were evaluated by volume, centroid shift, Dice and Jaccard indices, and mean distance agreement (MDA). The margins required to account for motion were calculated. Results: The ce4DCT acquisitions substantially improved tumor visibility over the entire breathing cycle in 20 patients, according to the experts’ unanimous evaluation. The median contrast peak time was 54.5 s, and the washout plateau was observed at 70.3 s, with mean peak and plateau HU values of 292 ± 59 and 169 ± 25. The volumes from the commonly used procedure (ITV2) were significantly smaller than the ce4DCT volumes (ITV1) (p = 0.045). The median centroid shift was 4.7 mm. The ITV1-ITV2 overlap was 69% (Dice index), 53% (Jaccard index), and 2.89 mm (MDA), with the liver volumes showing significantly lower indices compared to the pancreatic volumes (p ≤ 0.011). The margins required to better encompass ITV1 were highly variable, with mean values ≥ 4 mm in all directions except for the left–right axis. Conclusions: The ce4DCT simulation was feasible, resulting in optimal tumor enhancement with minimal resource investment, while significantly mitigating uncertainties in SBRT planning by addressing poor visibility and respiratory motion. Triple-phase 3DCT with unenhanced 4DCT led to high variability in target delineation, making the isotropic margins ineffective.

Background: Stereotactic body radiotherapy (SBRT) has gained increasing interest in the treatment of locally advanced pancreatic cancer (LAPC), although its effectiveness has not been defined in randomized trials. This systematic review and meta-analysis aimed to compare clinical outcomes and treatment-related toxicity between SBRT and CFRT in LAPC. Methods: This analysis was performed in accordance with PRISMA guidelines (PROSPERO: CRD420251128943). MEDLINE and Scopus were searched for comparative studies published between January 2015 and July 2025. Five retrospective studies comprising 768 patients fulfilled the eligibility criteria. Pooled hazard ratios (HRs) were calculated for overall survival (OS) and progression-free survival (PFS), while risk ratios (RRs) were estimated for severe (grade ≥ 3) acute toxicity using random-effects models. Study quality was evaluated using the ROBINS-I tool. Results: No significant OS or PFS differences were observed between SBRT and CFRT. SBRT was associated with a lower incidence of severe acute toxicity. The overall risk of bias across studies was moderate. Conclusions: SBRT appears to achieve survival outcomes comparable to CFRT with a favorable acute toxicity profile in patients with LAPC. Nevertheless, the current evidence is limited by retrospective designs and heterogeneity, highlighting the need for prospective randomized trials to define the role of SBRT in this setting.