Gian Carlo Mattiucci

Background: Squamous cell carcinoma (SCC) of the oral vestibule is associated with significant surgical challenges, often requiring extensive resections with functional and cosmetic sequelae. Interventional radiotherapy (IRT, brachytherapy) may provide a function‐preserving alternative. Methods: We retrospectively analyzed clinical data from 12 patients with primary oral vestibule SCC treated between February 2022 and March 2025. Eleven underwent high‐dose‐rate IRT (HDR‐IRT) with curative intent after multidisciplinary tumor board evaluation. Clinical outcomes, toxicity, and functional preservation were assessed. Results: Of the 11 patients treated with HDR‐IRT, ten achieved a complete response. At a mean follow‐up of 20 months, nine were alive and disease‐free. Two‐year disease‐specific survival and overall survival were 86% and 78%, respectively. Acute toxicity was limited to grade II mucositis, and long‐term sequelae were minimal, with only mild skin dyschromia. No patient developed trismus or Stensen's duct dysfunction. Conclusions: Exclusive HDR‐IRT appears to be a safe, effective, and organ‐preserving therapeutic option for selected oral vestibule SCCs; however, further studies in larger cohorts are needed to validate our findings.

Purpose: To evaluate the performance of eleven Knowledge-Based (KB) models for planning optimization (RapidPlan^tm (RP), Varian) of Volumetric Modulated Arc Therapy (VMAT) applied to whole breast comprehensive of nodal stations, internal mammary and/or supraclavicular regions. Methods and materials: Six RP models have been generated and trained based on 120 VMAT plans data set with different criteria. Two extra-structures were delineated: a PTV for the optimization and a ring structure. Five more models, twins of the previous models, have been created without the need of these structures. Results: All models were successfully validated on an independent cohort of 40 patients, 30 from the same institute that provided the training patients and 10 from an additional institute, with the resulting plans being of equal or better quality compared with the clinical plans. The internal validation shows that the models reduce the heart maximum dose of about 2 Gy, the mean dose of about 1 Gy and the V_20Gy of 1.5 Gy on average. Model R and L together with model B without optimization structures ensured the best outcomes in the 20% of the values compared to other models. The external validation observed an average improvement of at least 16% for the V_5Gy of lungs in RP plans. The mean heart dose and for the V_20Gy for lung IPSI were almost halved. The models reduce the maximum dose for the spinal canal of more than 2 Gy on average Conclusions: All KB models allow a homogeneous plan quality and some dosimetric gains, as we saw in both internal and external validation. Sub-KB models, developed by splitting right and left breast cases or including only whole breast with locoregional lymph nodes, have shown good performances, comparable but slightly worse than the general model. Finally, models generated without the optimization structures, performed better than the original ones.

Conventionally fractionated chemoradiation (CRT) or chemotherapy (CHT) are considered as standard options in locally advanced pancreatic cancer (LAPC) while stereotactic body radiotherapy (SBRT) is an emerging treatment in this setting. The aim of this study was to compare two cohorts of LAPC patients treated with SBRT ± CHT vs CRT ± CHT in terms of local control (LC), distant metastases‐free survival (DMFS), progression‐free survival (PFS), overall survival (OS), and toxicity. Eighty patients were included. Patients in the two cohorts were matched according to: age ≤/>65 years, tumor diameter (two cut‐offs: </≥3.0 and </≥3.9 cm), clinical tumor stage and clinical nodal stage, neoadjuvant CHT, and adjuvant CHT. Median prescribed total dose was 30.0 Gy (range: 18.0‐37.5) and 54.0 Gy (18.0‐63.0) in SBRT and CRT cohorts, respectively. Toxicity was evaluated by CTCAE v4.0 scale. Survival curves were calculated by Kaplan‐Meier method. For hypothesis testing an equivalence and a non‐inferiority test was calculated. No statistically significant differences in terms of acute and late toxicity, DMFS, PFS, and OS were recorded among the two cohorts. Median, 1‐, and 2‐year LC was: 16.0 months, 53.1%, and 40.5% in the CRT cohort and 22.0 months, 80.4%, and 49.8% in the SBRT cohort, respectively (P: .017). A statistically non‐inferiority significance was recorded in terms of OS between CRT and SBRT (P = .031). Patients treated with SBRT showed higher LC rate and similar OS compared to CRT. Therefore, the design of confirmatory randomized studies comparing SBRT and CRT seems justified.

To evaluate the impact of radiation dose on overall survival (OS) in patients treated with adjuvant chemoradiation (CRT) for pancreatic ductal adenocarcinoma (PDAC). A multicenter retrospective analysis on 514 patients with PDAC (T1–4; N0–1; M0) treated with surgical resection with macroscopically negative margins (R0–1) followed by adjuvant CRT was performed. Patients were stratified into 4 groups based on radiotherapy doses (group 1: < 45 Gy, group 2: ≥ 45 and < 50 Gy, group 3: ≥ 50 and < 55 Gy, group 4: ≥ 55 Gy). Adjuvant chemotherapy was prescribed to 141 patients. Survival functions were plotted using the Kaplan-Meier method and compared through the log-rank test. Median follow-up was 35 months (range: 3–120 months). At univariate analysis, a worse OS was recorded in patients with higher preoperative Ca 19.9 levels (≥ 90 U/ml; p < 0.001), higher tumor grade (G3–4, p = 0.004), R1 resection (p = 0.004), higher pT stage (pT3–4, p = 0.002) and positive nodes (p < 0.001). Furthermore, patients receiving increasing doses of CRT showed a significantly improved OS. In groups 1, 2, 3, and 4, median OS was 13.0 months, 21.0 months, 22.0 months, and 28.0 months, respectively (p = 0.004). The significant impact of higher dose was confirmed by multivariate analysis. Increasing doses of CRT seems to favorably impact on OS in adjuvant setting. The conflicting results of randomized trials on adjuvant CRT in PDAC could be due to < 45 Gy dose generally used.

Objective: A multi arm phase I clinical trial was performed to define the maximum tolerated dose (MTD) of stereotactic body radiotherapy (SBRT) delivered by non-coplanar conformal beams or Volumetric Modulated Arc Therapy technique in 7 predefined clinical settings.Methods: The (a) and (b) arms investigated primary and metastatic lung cancer differentiated by site of onset, arm (c) included primary or metastatic lesions outside the thorax, the (d) and (e) arms were for in-field re-irradiation of recurrence, and finally, the (f) and (g) arms were for boost irradiation to the lesions after an adjuvant RT prescribed dose. A 4 months cut-off after previous irradiation course was fixed to distinguish the boost from the re-treatment (4 months, respectively). Patients were prospectively enrolled in study arms according to tumor site, clinical stage and previous treatment. The total dose prescribed to the isocenter, ranged from 20 to 50 Gy according to the protocol design and the doses per fraction ranged ...

Background Interventional radiotherapy (brachytherapy; IRT) reemerged in the last decades as a potentially useful tool in head and neck oncology after a set of clear technical improvements were developed. Methods Sixty‐one high dose ratio (HDR) IRT treatments were recommended and performed on 58 patients. We classified the cases into four relatively homogeneous groups based on the clinical needs that led to the recommended IRT. Also, we separately evaluated primary and recurrent cases. Results Disease‐specific survival was significantly different among the four treatment groups. The group with the best prognosis was the cohort treated locally by exclusive interstitial IRT for resectable midface malignancies (2‐year relapse‐free survival = 82%, disease‐specific survival = 89%). Conclusion HDR IRT is a valuable tool in well‐defined clinical situations and, in particular, in recurrences. In midface malignancies, it could become the preferred primary treatment.

Radiotherapy (RT) is a treatment option for advanced biliary tract cancer (BTC), often combined with sequential and/or concurrent chemotherapy. The use of modern RT techniques requires accurate clinical target volume (CTV) definition and delineation. However, guidelines for CTV delineation in BTC are lacking. Therefore, the aim of this study was to propose a computer tomography (CT) atlas for CTV definition of BTC. We previously proposed guidelines to define the nodal CTV (CTV‑N) in BTC. In this study, based on a literature analysis, we defined the margins to be added to the gross tumor volume (GTV; subclinical and microscopic disease) to define the primary tumor CTV (CTV‑T). An abdominal contrast enhanced planning CT scan was performed on three different patients with unresectable intrahepatic cholangiocarcinoma (CC), extrahepatic CC and gallbladder cancer. The GTV and anatomical reference structures were outlined on CT images. Then, based on our guidelines, the CTV‑T and CTV‑N were delineated and merged to define the final CTV in the three patients. An atlas, showing the defined CTV, was generated from the reference CT images to illustrate the CTV for intra‑hepatic CC, extra‑hepatic CC and gallbladder cancer. This atlas can be used as an aid for CTV definition in patients with BTC treated with modern RT techniques.