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Purpose: Re-irradiation (re-RT) for recurrent intracranial meningiomas is hindered by the limited radiation tolerance of surrounding tissue and the risk of side effects. This study aimed at assessing outcomes, toxicities and prognostic factors in a cohort of patients with recurrent meningiomas re-treated with different RT modalities., Materials and Methods: A multi-institutional database from 8 Italian centers including intracranial recurrent meningioma (RM) patients who underwent re-RT with different modalities (SRS, SRT, PT, EBRT) was collected. Biologically Equivalent Dose in 2 Gy-fractions (EQD2) and Biological Effective Dose (BED) for normal tissue and tumor were estimated for each RT course (α/β = 2 for brain tissue and α/β = 4 for meningioma). Primary outcome was second progression-free survival (s-PFS). Secondary outcomes were overall survival (OS) and treatment-related toxicity. Kaplan-Meier curves and Cox regression models were used for analysis., Results: Between 2003 and 2021 181 patients (pts) were included. Median age at re-irradiation was 62 (range 20-89) and median Karnofsky Performance Status (KPS) was 90 (range 60-100). 78 pts were identified with WHO grade 1 disease, 65 pts had grade 2 disease and 10 pts had grade 3 disease. 28 pts who had no histologic sampling were grouped with grade 1 patients for further analysis. Seventy-five (41.4 %) patients received SRS, 63 (34.8 %) patients SRT, 31 (17.1 %) PT and 12 (6.7 %) EBRT. With a median follow-up of 4.6 years (interquartile range 1.7-6.8), 3-year s-PFS was 51.6 % and 3-year OS 72.5 %. At univariate analysis, SRT (HR 0.32, 95 % CI 0.19-0.55, p < 0.001), longer interval between the two courses of irradiation (HR 0.37, 95 % CI 0.21-0.67, p = 0.001), and higher tumor BED (HR 0.45 95 % CI 0.27-0.76, p = 0.003) were associated with longer s-PFS; in contrast, Ki67 > 5 % (HR 2.81, 95 % CI 1.48-5.34, p = 0.002) and WHO grade > 2 (HR 3.08, 95 % CI 1.80-5.28, p < 0.001) were negatively correlated with s-PFS. At multivariate analysis, SRT, time to re-RT and tumor BED maintained their statistically significant prognostic impact on s-PFS (HR 0.36, 95 % CI 0.21-0.64, p < 0.001; HR 0.38, 95 % CI 0.20-0.72, p = 0.003 and HR 0.31 95 % CI 0.13-0.76, p = 0.01, respectively). Acute and late adverse events (AEs) were reported in 38 (20.9 %) and 29 (16 %) patients. Larger tumor GTV (≥10 cc) was significantly associated with acute and late toxicity (p < 0.001 and p = 0.009, respectively)., Conclusions: In patients with recurrent meningiomas, reirradiation is a feasible treatment option associated with acceptable toxicity profile. Prognostic factors in the decision-making process have been identified and should be incorporated in daily practice., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Post-mastectomy radiotherapy (PMRT) improves local control rates and survival in patients with adverse prognostic features. The dose coverage to target volumes is critical to yield maximum benefit to treated patients, increasing local control and reducing risk of toxicity. This study aims to assess patterns of breast cancer relapse in patients treated with mastectomy, breast reconstruction and PMRT., Methods: Breast cancer patients treated with PMRT between 1992 and 2017 were retrospectively reviewed. Clinical and pathological characteristics of patients were collected. Recurrences were defined as "in field," "marginal" or "out of field." Survival analyses were performed in relation to progression-free survival (PFS) and overall survival (OS). Correlation between baseline features was explored., Results: Data of 140 patients are collected. After a median follow-up time of 72 months, median PFS and OS of 63 and 74 months were detected, respectively. Neoadjuvant chemotherapy, lympho-vascular space invasion (LVI) and size of primary tumor were all significantly associated with worst PFS and OS. Ten patients developed local recurrence: 30% "in field," 30% marginal recurrences, 20% "out of field" and 20% both "in field" and "out of field." No recurrence was detected under the expander, 80% above the device and 20% patients relapsed on IMN chain. The mean distant relapse-free survival was 39 months. Overall, 39 of 140 patients developed distant metastases., Conclusions: The onset of local-regional relapses occurred mainly above the expander/prosthesis, underlying the importance of inclusion of the subcutaneous tissues within the target volume. In order to refine new contouring recommendations for PMRT and breast reconstruction, future prospective studies are needed., (© 2024. The Author(s).)

Background: In the randomized phase II REGOMA trial, regorafenib showed promising activity in patients with recurrent glioblastoma. We conducted a large, multicenter, prospective, observational study to confirm the REGOMA data in a real-world setting., Patients and Methods: The major inclusion criteria were histologically confirmed diagnosis of glioblastoma according to the World Health Organization (WHO) 2016 classification and relapse after radiotherapy with concurrent/adjuvant temozolomide treatment, good performance status [Eastern Cooperative Oncology Group performance status (ECOG PS 0-1)] and good liver function. Regorafenib was administered at the standard dose of 160 mg/day for 3 weeks on/1 week off. Brain magnetic resonance imaging was carried out within 14 days before starting regorafenib and every 8-12 weeks. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective response rate, disease control rate (DCR), safety and health-related quality of life. The Response Assessment in Neuro-Oncology (RANO) criteria were used for response evaluation and Common Terminology Criteria for Adverse Events (CTCAE) version 5 for assessment of adverse events (AEs)., Results: From September 2020 to October 2022, 190 patients with recurrent glioblastoma were enrolled from 30 cancer centers in Italy: their median age was 58.5 years [interquartile range (IQR) 53-67 years], 68% were male and 85 (44.7%) were in optimal clinical condition (ECOG PS 0). The number of patients taking steroids at baseline was 113 (60%); the second surgery was carried out in 39 (20.5%). O 6 -methylguanine-DNA methyltransferase (MGMT) was methylated in 80 patients (50.3%) and 147 (92.4%) of the patients analyzed had isocitrate dehydrogenase (IDH) wild type. The median follow-up period was 20 months (IQR 15.6-25.5 months). The median OS was 7.9 months ([95% confidence interval (CI) 6.5-9.2 months] and the median PFS was 2.6 months (95% CI 2.3-2.9 months). Radiological response was partial response and stable disease in 13 (7.3%) and 26 (14.6%) patients, respectively, with a DCR of 21.9%. The median number of regorafenib cycles per patient was 3 (IQR 2.0-4.0). Grade 3-4 drug-related adverse events were reported in 22.6% of patients. A dose reduction due to AEs was required in 36% of patients. No deaths were considered as treatment-related AEs., Conclusions: This large, real-world observational study showed similar OS with better tolerability of regorafenib in patients with relapsed glioblastoma compared with the REGOMA study., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Recurrent salivary gland carcinomas (RSCs) are poorly characterized and their clinical features and treatment options have not yet been fully described. The goal of this study was to analyze the therapeutic strategies and oncological outcomes of RSC patients through a literature review analysis. This systematic review was performed according to the PRISMA statements. Inclusion criteria for the systematic review were based on the population, intervention, comparison, and outcomes according to (PICO) framework. Two thousand seven hundred and four records were selected and 1817 recurrences were studied. Three hundred and sixty-five patients underwent salvage surgery (20.1%) and their 5-year mortality rate, overall survival and disease-free survival were 35%, 70%, and 42%, respectively. RSCs are aggressive neoplasms with a high rate of distant metastases (28.9%). Salvage surgery can be considered in patients with limited local and/or regional recurrences, even in case of single distant relapse, appearing within the first 3 years of follow-up., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Background: High-grade gliomas are among the most aggressive central nervous system primary tumors, with a high risk of recurrence and a poor prognosis. Re-operation, re-irradiation, chemotherapy are options in this setting. No-best therapy has been established. Bevacizumab was approved on the basis of two Phase 2 trials that evaluated its efficacy in patients with recurrent glioblastoma., Materials and Methods: We have retrospectively review data of patients with high-grade glioma treated at our institution that undergone radiological or histological progression after at least one systemic treatment for recurrent disease. Bevacizumab was administered alone or in combination with chemotherapy until disease progression or unacceptable toxicity. Bevacizumab regimen was analyzed to assess PFS and OS. Histological, molecular and clinical features of the entire cohort were collected., Results: We reviewed data from 92 patients, treated from April 2009 to November 2019, with histologically confirmed diagnosis of high-grade gliomas and recurrent disease. A PFS of 55.2%, 22.9% and 9.6% was observed at 6, 12 and 24 months, respectively. Performance status, age at diagnosis (< 65 or > 65 ys.) and use of corticosteroids during bevacizumab therapy were strongly associated with PFS. The OS was 74.9% at 6 months, 31.7% at 12 months, 10.1% at 24 months. In our cohort, 51.1% were long-term responders (PFS > 6 months). Globally, bevacizumab treatment was well tolerated., Conclusion: Our analysis confirms the efficacy of bevacizumab in recurrent high-grade glioma patients with an acceptable toxicity profile, in keeping with its known safety in the literature., (© 2021. The Author(s).)

GBM (glioblastoma multiforme) is the most common and aggressive brain tumor. To date, treatment options for glioblastoma recurrence are lacking. Recently, REGOMA trial showed the superiority of regorafenib to lomustine in patients with first glioblastoma recurrence. We report an excellent response to three months treatment with regorafenib, in a patient who presented a rapid progression after the end of post operative radio-chemotherapy and after only one cycle of adjuvant TMZ (Temozolomide)., (Copyright © 2020. Published by Elsevier Ltd.)

Background: To report the long-term outcome of patients undergoing re-irradiation (re-RT) for a recurrent or second primary head and neck cancer (RSPHNCs) in seven Italian tertiary centers, while testing the Multi-Institution Reirradation (MIRI) recursive partitioning analysis (RPA) recently published., Methods: We retrospectively analyzed 159 patients. Prognostic factors for overall survival (OS) selected by a random forest model were included in a multivariable Cox analysis. To externally validate MIRI RPA, we estimated the Kaplan-Meier group-stratified OS curves for the whole population., Results: Five-year OS was 43.5% (median follow-up: 49.9 months). Nasopharyngeal site, no organ dysfunction, and re-RT volume <36 cm 3 were independent factors for better OS. By applying the MIRI RPA to our cohort, a Harrell C-Index of 0.526 was found indicating poor discriminative ability., Conclusion: Our data reinforce the survival benefit of Re-RT for selected patients with RSPHNC. MIRI RPA was not validated in our population., (© 2019 Wiley Periodicals, Inc.)

Urothelial cancer is one of the most common malignancies; after relapse or disease progression available therapeutic options are limited. We analyze efficacy and toxicity of local treatment on metastases using stereotactic body radiation therapy (SBRT) in selected patients with oligometastatic disease from urothelial cancer. A significant percentage of treated lesions achieved local control, with a promising overall response rate., Objectives: to analyze efficacy and toxicity of local treatment on metastases using stereotactic body radiation therapy (SBRT) in selected patients with oligometastatic disease from urothelial cancer., Materials and Methods: Data from clinical records of 19 patients treated in our institution since May 2011 to October 2017 with SBRT for oligometastatic/oligoprogressive urothelial carcinoma were retrospectively collected. Clinical outcomes in terms of local control (LC), response rate, symptoms control, progression free and overall survival (PFS and OS), and adverse events were analyzed and reported., Results: Nineteen patients were treated on 25 metastatic lesions; 5 of them received treatment on multiple sites. After an average follow up of 11.5 months, LC was achieved in 17 lesions (68%) and there was no local recurrence in lesions with complete or partial response. OS was 13.8 months. Adverse events were reported only in 3 patients (5 overall events). No late toxicity was reported., Conclusions: An approach consisting in SBRT for local treatment of oligometastatic or persistent disease can be effective and safe in selected patients. Prospective studies are needed, to find correct selection criteria and optimal dose and fractionation., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction:: This retrospective study analyzes the safety and feasibility of concurrent chemoradiotherapy (CRT) in adjuvant treatment of soft tissue sarcoma (STS)., Methods:: A total of 158 patients with STS were retrospectively analyzed. Anthracycline-based computed tomography was performed in high-risk patients. Acute radiotherapy toxicity and chemotherapy-related toxicity were assessed according to the Common Terminology Criteria for Adverse Events 4.0; late radiotherapy toxicity was recorded according to Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer criteria., Results:: Fifty-four (34.2%) patients received CRT. Mean follow up was 5.4 years (range .2-21.1 years). Local DFS-recurrence-free survival, distant DFS-relapse-free survival, and overall survival were 79.1%, 76.4%, and 64.6%, respectively, at last follow-up. Leukopenia occurred in 11.4% of patients. Skin acute toxicity developed in 60.1% of patients and determined interruption of radiotherapy treatment in 19 (12%) patients. Nineteen patients (12%) experienced moderate fibrosis (grade 2). Mild and moderate joint stiffness was recorded in 16 (10.1%) patients. Size ≥5 cm was the only predictor of local recurrence at multivariate analysis (hazard ratio [HR] 9.65, 95% confidence interval [CI] 1.28-72.83, p = .028). Age and stage resulted as independent distant relapse predictors (HR 4.77, 95% CI 1.81-12.58, p = .002 and HR 4.83, CI 1.41-16.57, p = .012, respectively). At Cox regression univariate analysis, Karnofsky Performance Status, size, and stage were significant survival predictors (HR 2.23, 95% CI 1.02-4.87, p = .045; HR 2.88, 95% CI 1.10-7.52, p = .031; HR 2.59, 95% CI 1.11-6.04, p = .028)., Conclusions:: Concurrent CRT is a well-tolerated treatment option with no additional toxicity compared to exclusive radiotherapy or sequential CRT.

The primary aim of this review is to provide practical recommendations in terms of fractionation, dose, constraints and selection criteria to be used in the daily clinical routine. Based on the analysis of the literature reviewed, in order to keep the risk of severe side effects ≤3,5%, patients should be stratified according to the target volume. Thus, patients should be treated with different fractionation and total EQD2 (<12.5 ml: EQD2 < 65 Gy with radiosurgery; >12.5 ml and <35 ml: EQD2 < 50 Gy with hypofractionated stereotactic radiotherapy; >35 ml and <50 ml: EQD2 < 36 Gy with conventionally fractionated radiotherapy). Concurrent approaches with temozolomide or bevacizumab do not seem to improve the outcomes of reirradiation and may lead to a higher risk of toxicity but these findings need to be confirmed in prospective series., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Aims: Robotic stereotactic body radiotherapy (rSBRT) to local recurrences emerged as a valuable option for exclusive local failure after prior external beam radiation therapy (EBRT) for localised prostate cancer. The aim of this study was to assess the efficacy and safety of rSBRT in patients experiencing locally recurrent prostate cancer after prior definitive or postoperative radiotherapy using the Cyberknife., Materials and Methods: Data from 50 patients were retrospectively reviewed. Local recurrence was assessed by 18F-choline positron emission tomography and pelvic magnetic resonance imaging; a dose of 30 Gy was delivered in five fractions. Prostate-specific antigen (PSA) was assessed at 2 months, 6 months and every 4 months thereafter. Toxicity was assessed according to CTCAE v.4.03., Results: All patients received prior EBRT. The median EQD2 total dose was 74 Gy (60-80 Gy). Eleven patients were receiving androgen deprivation after prior biochemical failure. At 6 months, 41 patients showed a median PSA decline of -77.1% (14.3-99.3%), whereas nine patients experienced a median PSA elevation of +58.7% (0-2300.0%). Biochemical relapse-free survival (BRFS) was 80.0%. Impaired BRFS was correlated with the high-risk category at diagnosis (P = 0.014, hazard ratio 5.61) and ongoing androgen deprivation (P = 0.025, hazard ratio 2.98). Neither clinical variables nor dosimetric parameters were found to be predictive for toxicity., Conclusion: Focal rSBRT can achieve durable remission in locally relapsing patients and systemic treatment can be postponed with acceptable toxicity. Accurate patient selection is mandatory to maximise disease control., (Copyright © 2017 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background: Stereotactic body radiotherapy (SBRT) emerged as a treatment option in oligometastatic (≤3 metastases) patients experiencing lymph node relapse from treated prostate cancer. No recommendations are available concerning dose schedule, and available studies report the use of multiple-fraction regimens due to theoretical lower toxicity and higher cumulative dose delivered to the target. The aim of the present study was to evaluate the safety and efficacy of a dose-intensive, single-fraction SBRT regimen., Patients and Methods: Retrospective data on outcome and toxicity from 27 treatments on 23 consecutive patients were collected. Statistical analysis was performed., Results: Median follow-up was 22 months (range 6-63, interquartile range 15-28). Biochemical progression-free survival (bPFS) at 6 months, 1 year, and 2 years were 65%, 40%, and 26%, respectively. In 2 cases acute toxicity of grade 1 were observed., Conclusion: Single-fraction SBRT for lymph node relapse of oligometastatic prostate cancer resulted in promising biochemical control with minimal toxicity., (© 2018 S. Karger GmbH, Freiburg.)

Aims and Background: Radiobiological and technical considerations have traditionally limited the role of radiation therapy in the context of primary and secondary cardiac malignancies. Stereotactic body radiotherapy (SBRT) is a promising modality for the delivery of focused high-dose radiation with ablative potential to complex targets such as small, deep-seated, moving lesions, allowing also for re-irradiation., Methods: Between January 2013 and October 2013, 3 patients underwent SBRT for cardiac lesions: 2 patients had recurrent, previously irradiated cardiac angiosarcomas (PCA) and 1 patient had a cardiac metastasis from melanoma. They were treated with fiducial-guided robotic radiotherapy with CyberKnife. As for dose prescription, 24 Gy in 3 fractions (80% isodose) and 30 Gy in 5 fractions (80% isodose) were administered to the recurrent PCAs and cardiac metastasis, respectively., Results: At 2 months after SBRT, cardiac MRI showed a partial response in the patients treated for recurrent PCA while the cardiac metastasis remained stable. In all cases, absence of local progression was subsequently confirmed by contrast-enhanced cardiac MRI after 6 months, without any evidence of treatment-related side effects., Conclusions: Fiducial-guided SBRT proved to be feasible and effective in preventing local disease progression in selected patients with cardiac malignancies.

Purpose: To investigate the outcome of invasive early breast cancer patients that underwent breast-conserving surgery and adjuvant radiotherapy (RT), treated with a prospective margin-directed institutional policy for RT boost dose, based on final margins status (FMS)., Methods and Materials: A total of 2093 patients were treated between 2000 and 2008. 10 Gy boost was prescribed in case of FMS>5mm; 16 Gy boost with FMS between 2 and 5mm; 20 Gy boost in case of FMS<2mm or positive., Results: After a median follow up of 5.2 years, we recorded 41 local relapse (LR, 2%). Concerning LR free survival, age at diagnosis, nuclear grade, hormonal status, T-stage, adjuvant hormonal therapy and adjuvant chemotherapy emerged as significant parameters (p-values from log rank test <0.05). FMS, that directed the RT boost dose, did not have significant impact on LRFS (p=0.46). LR rates were 2.3% for FMS<2mm, 2.6% for 2-5mm FMS and 1.8% for FMS>5mm. At multivariate analysis, higher nuclear grade (p=0.045), triple negative subtype (p=0.036) and higher T-stage (p=0.02) resulted as the independent predictors of LR occurrence., Conclusions: Our experience showed that a margin-directed policy of RT boost dose-escalation seems to reduce the negative impact of FMS on LR, but it is not able to overcome the unfavorable effect of higher nuclear grade, higher T stage and triple negative subtype., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)