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Purpose: One of the main limiting factors of whole-brain radiation therapy (WBRT) for primary central nervous system lymphoma (PCNSL) is the impairment of neurocognitive functions (NCFs), which is mainly caused by radiation-induced injury to the hippocampus. With a view to preventing NCF impairment and personalizing treatment, we explored the feasibility of sparing the hippocampus during WBRT by correlating the sites of PCNSL lesions with the hippocampus., Methods and Materials: Pre-treatment MR images from patients who underwent WBRT between 2010 and January 2020-and post-radiotherapy images in cases of relapse-were imported into the Varian Eclipse treatment-planning system and registered with the simulation CT. We constructed three 3-dimensional envelopes around the hippocampus at distances of 5, 10 and 15 mm and also contoured primary lesions and recurrences., Results: We analyzed 43 patients with 66 primary lesions: 9/66 (13.6%) involved the hippocampus and 11/66 (16.7%) were located within 5 mm of it. Thirty-six lesions (54.5%) were situated more than 15 mm from the hippocampus, while 10/66 (15.2%) were between 5 and 15 mm from it. The most common location was in deep brain structures (31%). Thirty-five of the 66 lesions relapsed: in field in 14/35 (40%) and outfield in 21/35 (60%) in different sites. Globally, 16/35 recurrences (45.7%) were located in the hippocampus or within 5 mm of it., Conclusion: These data show that routinely sparing the hippocampus is not feasible. This approach could be considered in selected patients, when the lesion is more than 15 mm from the hippocampus., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Aims: Reirradiation of prostate cancer (PC) local recurrences represents an emerging challenge for current radiotherapy. In this context, stereotactic body radiation therapy (SBRT) allows the delivery of high doses, with curative intent. Magnetic Resonance guided Radiation Therapy (MRgRT) has shown promising results in terms of safety, feasibility and efficacy of delivering SBRT thanks to the enhanced soft tissue contrast and the online adaptive workflow. This multicentric retrospective analysis evaluates the feasibility and efficacy of PC reirradiation, using a 0.35 T hybrid MR delivery unit., Methods: Patients affected by local recurrences of PC and treated in five institutions between 2019 and 2022 were retrospectively collected. All patients had undergone previous Radiation Therapy (RT) in definitive or adjuvant setting. Re-treatment MRgSBRT was delivered with a total dose ranging from 25 to 40 Gy in 5 fractions. Toxicity according to CTCAE v 5.0 and treatment response were assessed at the end of the treatment and at follow-up., Results: Eighteen patients were included in this analysis. All patients had previously undergone external beam radiation therapy (EBRT) up to a total dose of 59.36 to 80 Gy. Median cumulative biologically effective dose (BED) of SBRT re-treatment was 213,3 Gy (103,1-560), considering an α/β of 1.5. Complete response was achieved in 4 patients (22.2%). No grade ≥ 2 acute genitourinary (GU) toxicity events were recorded, while gastrointestinal (GI) acute toxicity events occurred in 4 patients (22.2%)., Conclusion: The low rates of acute toxicity of this experience encourages considering MRgSBRT a feasibile therapeutic approach for the treatment of clinically relapsed PC. Accurate gating of target volumes, the online adaptive planning workflow and the high definition of MRI treatment images allow delivering high doses to the PTV while efficiently sparing organs at risk (OARs)., (© 2023. The Author(s).)

Background: To evaluate the impact of radiation dose on overall survival (OS) in patients treated with adjuvant chemoradiation (CRT) for pancreatic ductal adenocarcinoma (PDAC)., Methods: 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., Results: 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., Conclusions: 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.

Background: Different studies have proved in recent years that hypofractionated radiotherapy (RT) improves overall survival of patients affected by locally advanced, unresectable, pancreatic cancer. The clinical management of these patients generally leads to poor results and is considered very challenging, due to different factors, heavily influencing treatment delivery and its outcomes. Firstly, the dose prescribed to the target is limited by the toxicity that the highly radio-sensitive organs at risk (OARs) surrounding the disease can develop. Treatment delivery is also complicated by the significant inter-fractional and intra-fractional variability of therapy volumes, mainly related to the presence of hollow organs and to the breathing cycle. The recent introduction of magnetic resonance guided radiotherapy (MRgRT) systems leads to the opportunity to control most of the aforementioned sources of uncertainty influencing RT treatment workflow in pancreatic cancer. MRgRT offers the possibility to accurately identify radiotherapy volumes, thanks to the high soft-tissue contrast provided by the Magnetic Resonance imaging (MRI), and to monitor the tumour and OARs positions during the treatment fraction using a high-temporal cine MRI. However, the main advantage offered by the MRgRT is the possibility to online adapt the RT treatment plan, changing the dose distribution while the patient is still on couch and successfully addressing most of the sources of variability., Short Conclusion: Aim of this study is to present and discuss the state of the art, the main pitfalls and the innovative opportunities offered by online adaptive MRgRT in pancreatic cancer treatment.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.

Gastroesophageal cancers (such as esophageal, gastric and gastroesophageal-junction -GEJ- lesions) are worldwide a leading cause of death being relatively rare but highly aggressive. In the past years, a clear shift in the location of upper gastrointestinal tract tumors has been recorded, both affecting the scientific research and the modern clinical practice. The integration of pre- or peri-operative multimodal approaches, as radiotherapy and chemotherapy (often combined), seems promising to further improve clinical outcome for such presentations. In the past, the definition of GEJ led to controversies and confusion: GEJ tumors have been managed either grouped to gastric or esophageal lesions, following slightly different surgical, radiotherapeutic and systemic approaches. Recently, the American Joint Committee on Cancer (AJCC) changed the staging and classification system of GEJ to harmonize some staging issues for esophageal and gastric cancer. This review discusses the most relevant historical and recent evidences of neoadjuvant treatment involving Radiotherapy for GEJ tumors, and describes the efficacy of such treatment in the frame of multimodal integrated therapies, from the new point of view of the recent classification of such tumors.