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Introduction: To evaluate the feasibility, efficacy and safety of stereotactic ablative radiotherapy (SABR) to the primary tumor and lymph nodes in patients with locally advanced non-small cell lung cancer (LA-NSCLC) who are ineligible for or refused concomitant chemoradiation., Materials and Methods: In accordance with the PRISMA and MOOSE guidelines, a systematic review with meta-analysis was conducted. The study included reports that assessed the outcomes of SABR treatment in patients with LA-NSCLC. Studies evaluating SBRT as a boost following primary radiotherapy were excluded. The primary outcomes measured were local control (LC) and overall survival (OS). The secondary endpoint was the incidence of severe toxicity (grades 3-5). A meta-regression analysis was performed to explore the relationship between LC, OS, and severe toxicity. The Biologically Effective Dose (BED) was analyzed as a continuous variable. Statistical significance was defined as a p-value < 0.05., Results: A total of seven studies (3 prospective and 4 retrospective studies) involving 268 patients (SBRT to primary and lymph nodes) were included in the analysis. The pooled 1-year LC rate was 80 % (95 % CI: 63-94 %), and the factors significantly associated with LC were BEDGy10 (p = 0.005) and neoadjuvant chemotherapy (p = 0.005). The 1-year and 2-year OS rates were 74 % (95 % CI: 58-90 %) and 55 % (95 % CI: 34-76 %), respectively. Meta-regression analysis indicated a linear relationship between OS and LC, with a 0.7 % increase in OS for each 1 % improvement in LC (p = 0.005). The pooled rate of grade 3 acute toxicity was 5 % (95 % CI: 1-10 %), and the rate of grade 5 toxicity was 1.7 % (95 % CI: 0-3 %)., Conclusion: Promising results (LC and OS) with limited toxicity (feasibility) using SABR in LA-NSCLC warrant further research, emphasizing the need for larger, well-designed trials for further validation of the approach., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: FYM reports previous consulting fee from Elekta and honoraria from Astra Zeneca, both outside the current work., (Copyright © 2024. Published by Elsevier B.V.)

Background: Diffuse intrinsic pontine glioma (DIPG) stands as the predominant type of brainstem glioma. It is characterized by a notably brief median survival period, with the majority of patients experiencing disease progression within six months following radiation therapy. This systematic review and meta-analysis aims to assess the efficacy and safety of hypofractionated radiotherapy (HFRT) compared to conventionally fractionated radiotherapy (CFRT) in DIPG treatment., Materials and Methods: A systematic literature search was conducted in four databases, and relevant studies comparing HFRT and CFRT in DIPG were included. Data were extracted and analyzed for overall survival (OS), progression-free survival (PFS), and treatment-related toxicities. Statistical analysis was performed using random-effects models with heterogeneity assessment., Results: Five studies met the inclusion criteria, comprising 518 patients. No significant difference in one-year OS was observed between HFRT and CFRT (29% vs. 22%, p = 0.94). The median OS was similar in both treatment groups (9.7 vs. 9.3 months, p = 0.324). Similarly, no significant difference in one-year PFS was found between HFRT and CFRT (19.8% vs. 16.6%, p = 0.82), with comparable median PFS (9.3 vs. 9.4 months, p = 0.20). In meta-regression analysis, there was no association of chemotherapy (p > 0.05) or radiation biologically effective dose (BED) (p > 0.05) regarding OS or PFS outcomes. There were no significant differences in treatment-related toxicities., Conclusions: HFRT yields one-year OS and PFS rates similar to CFRT in DIPG, with no significant differences in treatment-related toxicities. Chemotherapy and BED did not affect OS or PFS., Competing Interests: Conflict of interest: F.Y.M. reports previous consulting fee from Elekta and honoraria from Astra Zeneca, both outside the current work. G.N.M. reports previous honoraria from Varian and Astra Zeneca, both outside the current work. All other authors have no competing interests., (© 2024 Greater Poland Cancer Centre.)

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.)

Purpose: This is a single arm phase 2 trial (Clinical trials.gov NCT05291780) to assess local control (LC) and safety of SAbR in patients with unresectable locally advanced non-small cell lung cancer (LA-NSCLC) unfit for concurrent chemo-radiation therapy (ChT-RT)., Methods: Neoadjuvant ChT was prescribed in fit patients. The tumor volume included primary tumor and any regionally positive node/s. The coprimary study endpoints were LC and safety., Results: Between December 31, 2015, and December 31, 2020, 50 patients with LA-NSCLC were enrolled. Histology was squamous cell carcinoma and adenocarcinoma (ADC) in 52% and 48%, respectively. Forty (80%) patients had ultracentral tumor. Twenty-seven (54%) received neoadjuvant ChT and 7 (14%) adjuvant durvalumab. Median prescribed dose was 45 Gy (range, 35-55) and 40 Gy (35-45) in 5 daily fractions to tumor and node/s, respectively. After a median follow-up of 38 months (range, 12-80), 19 (38%) patients had experienced local recurrence (LR) at a median time of 13 months (range, 7-34). The median LR-free survival (FS) was not reached (95% confidence interval [CI], 28 to not reached). The 1-, 2-, and 3-year LR-FS rates were 86% ± 5%, 66% ± 7%, and 56% ± 8%, respectively. At last follow-up, 33 (66%) patients were alive. Median overall survival (OS) was 55 months (95% CI, 43-55 months). The 1-, 2-, and 3-year OS rates were 94% ± 3%, 79% ± 6%, and 72% ± 7%, respectively. No patients developed ≥ grade (G) 3 toxicity. ADC (hazard ratio [HR], 3.61; 95% CI, 1.15-11.35) was a significant predictor of better LC, while OS was significantly conditioned by smaller planning target volumes (HR, 1.004; 95% CI, 1.001-1.010) and tumor, node, and metastasis stage (HR, 4.8; 95% CI, 1.34-17)., Conclusions: Patients with LA-NSCLC treated with SABR had optimal LC and promising OS in absence of ≥G3 toxicity. Our early outcomes would suggest the feasibility of using this approach in patients with LA-NSCLC unfit for concurrent ChT-RT., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice., Method: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations., Results: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders., Conclusions: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine.

Brain metastases, the most common metastases in adults, will develop in up to 40% of cancer patients, accounting for more than one-half of all intracranial tumors. They are most associated with breast and lung cancer, melanoma and, less frequently, colorectal and kidney carcinoma. Magnetic resonance imaging (MRI) is the gold standard for diagnosis. For the treatment plan, computed tomography (CT ) images are co-registered and fused with a gadolinium-enhanced T1-weighted MRI where tumor volume and organs at risk are contoured. Alternatively, plain and contrast-enhanced CT scans are co-registered. Single-fraction stereotactic radiotherapy (SRT ) is used to treat patients with good performance status and up to 4 lesions with a diameter of 30 mm or less that are distant from crucial brain function areas. Fractionated SRT (2-5 fractions) is used for larger lesions, in eloquent areas or in proximity to crucial or surgically inaccessible areas and to reduce treatment-related neurotoxicity. The single-fraction SRT dose, which depends on tumor diameter, impacts local control. Fractionated SRT may encompass different schedules. No randomized trial data compared the safety and efficacy of single and multiple fractions. Both single-fraction and fractionated SRT provide satisfactory local control rates, tolerance, a low risk of transient acute adverse events and of radiation necrosis the incidence of which correlated with the irradiated brain volume., Competing Interests: Conflicts of interest The authors have no conflict of interest to declare., (© 2022 Greater Poland Cancer Centre.)

Background: To define efficacy and toxicity of Immunotherapy (IT) with stereotactic radiotherapy (SRT) including radiosurgery (RS) or hypofractionated SRT (HFSRT) for brain metastases (BM) from non-small cell lung cancer (NSCLC) in a multicentric retrospective study from AIRO (Italian Association of Radiotherapy and Clinical Oncology)., Methods: NSCLC patients with BM receiving SRT + IT and treated in 19 Italian centers were analyzed and compared with a control group of patients treated with exclusive SRT., Results: One hundred patients treated with SRT + IT and 50 patients treated with SRT-alone were included. Patients receiving SRT + IT had a longer intracranial Local Progression-Free Survival (iLPFS) (propensity score-adjusted P = .007). Among patients who, at the diagnosis of BM, received IT and had also extracranial progression (n = 24), IT administration after SRT was shown to be related to a better overall survival (OS) (P = .037). A multivariate analysis, non-adenocarcinoma histology, KPS = 70 and use of HFSRT were associated with a significantly worse survival (P = .019, P = .017 and P = .007 respectively). Time interval between SRT and IT ≤7 days (n = 90) was shown to be related to a longer OS if compared to SRT-IT interval >7 days (n = 10) (propensity score-adjusted P = .008). The combined treatment was well tolerated. No significant difference in terms of radionecrosis between SRT + IT patients and SRT-alone patients was observed. The time interval between SRT and IT had no impact on the toxicity rate., Conclusions: Combined SRT + IT was a safe approach, associated with a better iLPFS if compared to exclusive SRT., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: Despite the advances in surgery and radio-chemotherapy, the prognosis of glioblastoma (GBM) remains poor with about 13% of patients alive at 24 months., Methods: A total of 75 long-term survivors (LTS), defined as alive at least 24 months from diagnosis, were retrospectively analyzed. Overall survival (OS) and recurrence-free-survival (RFS) were calculated and related to patient characteristics and treatment received., Results: Median age and Karnofsky performance status (KPS) were 56 years and 100%, respectively. After surgery (gross tumor resection-GTR in 62, 83% patients), all LTS received concomitant temozolomide (TMZ) with radiotherapy and 70 (93%) adjuvant TMZ. Of these, 10 (13%) discontinued TMZ prior the completion of 6 cycles, 37 (49%) received 6 cycles and 23 (31%) >6 cycles. Sixty-nine (92%) patients experienced a first tumor recurrence at a median time of 21 months. Of these, 32 (46%) were submitted to a second surgery, 34 (49%) to other no-surgical treatments and 3 (5%) only supportive care. At multivariate analysis, OS was significantly improved by second surgery after first recurrence (P = 0.0032) and by cycles of adjuvant TMZ > 6 versus ≤6 (P = 0.05). More than six cycles of TMZ significantly conditioned also first RFS (P = 0.011) and second RFS (P = 0.033)., Conclusion: The large majority of LTS had <65 years, had a high KPS and received GTR. OS and RFS resulted significantly related to an extended administration of adjuvant TMZ (>6 cycles) and a second surgery in case of recurrence., (© 2020 John Wiley & Sons Australia, Ltd.)

Introduction: Oligometastatic disease has emerged as an intermediate state between localized and systemic cancer. Improvements in diagnostic modalities such as functional imaging allow a greater frequency of oligometastases diagnosis. Patients with selected oligometastatic epithelial ovarian carcinoma (EOC) may be treated with metastasis-directed stereotactic body radiotherapy (SBRT) rather than chemotherapy., Case Description: We describe a 58-year-old woman who underwent surgery and chemotherapy for an EOC. The patient underwent 3 chemotherapy lines for recurrence of disease, but had allergic reactions and serious hematologic toxicity. During follow-up, lymph node oligometastases were diagnosed and treated with repeated SBRT because the patient refused further chemotherapy. No side effects were observed after each course of SBRT and the patient obtained complete response of all irradiated sites., Conclusions: SBRT is a promising treatment approach for recurrent oligometastatic EOC with a high control rate and irrelevant iatrogenic toxicity. The possibility to repeat SBRT courses when new oligometastases are encountered in other sites resulted in an adequate long-term palliation approach.

Objectives: The prognosis of brain metastatic colorectal cancer patients (BMCRC) is poor. Several local treatments have been used, but the optimal treatment choice remains an unresolved issue. We evaluated the clinical outcomes of a large series of BMCRC patients treated in several Italian centers using stereotactic radiosurgery (SRS)., Methods: 185 BMCRC patients for a total of 262 lesions treated were evaluated. Treatments included surgery followed by post-operative SRS to the resection cavity, and SRS, either single-fraction, then hypofractionated SRS (HSRS). Outcomes was measured in terms of local control (LC), toxicities, brain distant failure (BDF), and overall survival (OS). Prognostic factors influencing survival were assed too., Results: The median follow-up time was 33 months (range 3-183 months). Surgery plus SRS have been performed in 28 (10.7%) cases, SRS in 141 (53.8%), and HSRS in 93 (35.5%). 77 (41.6%) patients received systemic therapy. The main total dose and fractionation used were 24 Gy in single fraction or 24 Gy in three daily fractions. Local recurrence occurred in 32 (17.3%) patients. Median, 6 months,1-year-LC were 86 months (95%CI 36-86), 87.2% ± 2.8, 77.8% ± 4.1. Median,6 months,1-year-BDF were 23 months (95%CI 9-44), 66.4% ± 3.9, 55.3% ± 4.5. Median,6 months,1-year-OS were 7 months (95% CI 6-9), 52.7% ± 3.6, 33% ± 3.5. No severe neurological toxicity occurred. Stage at diagnosis, Karnofsky Performance Status (KPS), presence and number of extracranial metastases, and disease-specific-graded-prognostic-assessment (DS-GPA) score were observed as conditioning survival., Conclusion: SRS/HSRS have proven to be an effective local treatment for BMCRC. A careful evaluation of prognostic factors as well as a multidisciplinary evaluation is a valid aid to manage the optimal therapeutic strategy for CTC patients with BMs., Advances in Knowledge: The prognosis of BMCRC is poor. Several local treatments was used, but optimal treatment choice remains undefined. Radiosurgery has proven to be an effective local treatment for BMCRC. A careful evaluation of prognostic factors and a multidisciplinary evaluation needed.

Objective: To report our experience on stereotactic body radiotherapy (SBRT) in adrenal metastases from lung cancer., Methods: 37 oligometastatic lung cancer patients with 38 adrenal metastases submitted to SBRT were retrospectively analyzed. SBRT was delivered by volumetric modulated arc therapy (VMAT) or helical tomotherapy (HT). Primary study end point was local recurrence-free survival (LR-FS) and secondary end points were distant-progression free survival (d-PFS) and overall survival (OS)., Results: Median age was 67 years and primary tumor was non-small-cell lung cancer in 27 (73%) and small-cell lung cancer in 10 (27%) patients. Adrenal metastases were in the left side in 66% cases. Median prescribed dose was 30 Gy in 5 fractions for a median biologically equivalent dose (α/β ratio 10  Gy, BED10) of 48 Gy. Most patients (62%) were submitted to SBRT alone, while the others (38%) received chemo-, immune- or target- therapies. Median follow-up was 10.5 months, median OS 16 months and median d-PFS 3 months. 27 (70%) patients obtained a local control with a median LR-FS of 32 months. LR-FS was significantly related to BED10 with a better LC with BED10 ≥72 Gy, 1- and 2 year LR-FS rates were 54.1±11.6% and 45±12.7%  vs 100 and 100% for BED ≤59.5 Gy and BED ≥72 Gy, respectively ( p = 0.05). There was no severe toxicity., Conclusion: SBRT was effective and safe in lung cancer adrenal metastases. A dose-response relationship was found between BED10 > 72 Gy and better local control. No significant toxicity was registered thanks to the respect of dose constraints and suspension of chemo- and target-therapies., Advances in Knowledge: SBRT with a BED10 > 72 Gy is an effective treatment for adrenal oligometastatic lung cancer patients.

Background: The aim of this study was to report response, overall survival (OS) and toxicity in patients with radioresistant brain metastases (BM) treated with stereotactic radiosurgery (SRS)., Methods: Patients with renal cell carcinoma, melanoma and sarcoma with one to four brain metastases received SRS without whole brain radiotherapy., Results: Fifty patients with 77 BM were treated. 46 (92%) patients with 71 BM were evaluable. Median follow-up was 67 months and median OS 11.8 months. At the time of analysis all patients had died. Brain control was conditioned by response to SRS (P<0.0001), while OS by histology (renal cell carcinoma versus melanoma and sarcoma) (P=0.04) and status of the tumour outside the brain (P=0.05). Treatment was well tolerated without more than grade 2 acute toxicity., Conclusions: Treatment of BM from radioresistant tumors with SRS assures good brain control and OS with low toxicity. Our data suggest a better prognosis associated to renal cell carcinoma histology.

Purpose: To report long-term outcomes of 53 patients with vestibular schwannomas (VS) submitted to a single high-dose LINAC-based radiosurgery (SRS) in our institution., Methods: 48 (92%) patients were evaluable for clinical and MRI response as well as late toxicity. At a median follow-up of 12 years (range 2-16 years), local control (LC), hearing capacity, trigeminal and facial nerve function, and toxicity were assessed. Hearing capacity was classified according to the Gardner-Robertson scale, where class I-II patients had "serviceable hearing.", Results: Median dose of SRS was 16.5 Gy (range 13-20 Gy) and median tumor volume 1.7 cm 3 (range 0.09-7.4 cm 3 ). 35 (73%) patients were treated with SRS alone, in the remaining 13 (27%) patients, SRS was performed as salvage therapy for recurrent or progressive tumors after previous microsurgery. Before SRS, 44 patients (92%) had hearing loss and 25 (52%) had "non-serviceable" hearing. Tumor extension, classified with Koos categories, was grade I-II in 27 (56%) and grade III-IV in 21 (44%) cases. LC was 100% and hearing preservation in "serviceable hearing" patients was 91%. 4 (11%) patients developed incomplete and intermittent ipsilateral facial nerve palsy which regressed in a median time of 6 months. Trigeminal toxicity was registered in 11 (23%) patients, reversible in 6 (13%) and permanent in 5 (10%). Only Koos tumor grade III-IV significantly influenced late toxicity (p = 0.01)., Conclusion: LC and hearing preservation after SRS were excellent. Toxicity proved acceptable. Although the median administered dose (16.5 Gy) was rather high, the only factor which significantly influenced late toxicity was Koos tumor grade III-IV.

Purpose: The purpose of this study was to report mature clinical and cosmetic results of accelerated partial-breast irradiation with interstitial multicatheter high-dose-rate brachytherapy (HDR-BRT) in patients with early breast cancer., Methods and Materials: 133 patients were recruited in a Phase II trial of exclusive HDR-BRT. Inclusion criteria were age ≥40 years, PS 0-2, unifocal invasive ductal cancer, intraductal cancer component <25%, negative axillary nodes, and tumor size ≤2.5 cm. Treatment schedule was 4 Gy twice a day up to a total dose of 32 Gy in eight fractions., Results: Median age was 67 years (range, 42-85). There were 7 (5%) pT1a, 48 (36%) pT1b, 72 (54%) pT1c, and 6 (5%) pT2. Estrogen and progesterone receptors were positive in 119 (89%) and 93 (70%) patients, respectively. The median followup was 110 months (range, 12-163). After HDR-BRT, there were 3 (2%) in-field breast recurrences and 1 (1%) out-field breast recurrence. 5 (4%) patients developed contralateral breast cancer, another one (1%) isolated regional relapse in axillary node and 3 (2%) distant progression of disease. 19 (14%) patients reported a second primary cancer. 5-, 10-, and 13-year overall survival and cancer-specific survival were 95% and 100%, 84.5% and 100%, and 81.4% and 100%, respectively. Cosmetic outcome was excellent in 80% of cases. Late toxicity was significantly related to the skin administered doses (≤55% vs. > 55% of the prescribed dose, p < 0.05)., Conclusions: Accelerated partial-breast irradiation delivered with HDR-BRT in selected patients with breast cancer was associated to high local control and survival with excellent cosmetic outcomes overall when skin dose was ≤55%., (Copyright © 2019 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

Purpose: In our previous published trial on radiosurgery (SRS) of recurrent brain metastases (BM) after whole brain radiotherapy (WBRT), Karnofsky performance status (KPS) and administered dose conditioned outcome and late toxicity, respectively. Brain radionecrosis was registered in 6% of patients. With the aim to obtain similar satisfactory outcomes and limit toxicity, we started a phase II trial in which reirradiation of BM with SRS were done using a tighter patient selection., Materials and Methods: Patients with BM recurring after WBRT were recruited for reirradiation with SRS. Only patients with good KPS (≥70), good neurologic functional score (NFS 0-1) and lesions with a diameter ≤20 mm were considered eligible for retreatment. Dose exceeding 20 Gy was never administered., Results: The 59 patients reirradiated had 109 BM with a diameter range of 6-20 mm. Median interval between prior WBRT and SRS was 15 months and median SRS administered dose was 18 Gy (range 10-20 Gy). Complete and partial response (CR, PR) was obtained in 42% of patients with 2 years of control rate of 81%. Median overall survival (OS) after reirradiation was 14 months. No radionecrosis was detected., Conclusions: Analysis of our current trial compared with results of our previous data suggests that a tighter patient selection (KPS ≥ 70; NFS 0-1, BM with ≤20 mm of diameter) and SRS dose ≤20 Gy allowed a high OS rate, a good percentage of CR and PR which last for >2 years, and no brain radionecrosis.

Purpose: We report the long-term results of phase II prospective study with accelerated partial breast irradiation (APBI) using interstitial multi-catheter high-dose-rate brachytherapy., Methods: 240 patients received APBI (4Gy, twice daily; total dose 32Gy)., Results: Median follow-up was 96months. Recurrences in the treated breast developed in 8 patients (3.3%) at a median of 73months after APBI. The 5- and 10-year cumulative incidences were respectively, 1.8% (95%CI: 0.6-4.3) and 6.6% (95%CI: 2.7-12.9). Regional recurrences developed in 5 patients (2%) at a median of 28months and distant metastases in 8 (3.3%) at a median of 32.5months. Breast cancer specific mortality occurred in 6 patients (2.5%) at a median of 60months. Acute toxicity developed in 71 (29.6%) patients (G1 in 60 and G2 in 11). Almost all were skin toxicity and hematomas. Late toxicity was observed in 90 patients (37.5%), G1 in 97 cases and G2 in 11. Some patients presented with more than one type of toxicity. Teleangectasia and fibrosis were the most common (48 and 44 cases respectively), followed by fat necrosis (in 18 patients) Tamoxifen emerged as the only risk factor for breast fibrosis (p=0.007). Cosmetic results were judged by the physicians as excellent in 174 (83.7%) patients, good in 25 (12%) fair in 8 (3.8%) and poor in 1 (0.5%); 174 patients (83.7%) judged outcomes as excellent, 26 (12.4%) as good, 7 (3.4%) as fair and 1 (0.5%) as poor. Physician/patient agreement was good (weighted k-value 0.72)., Conclusions: APBI with interstitial multi-catheter brachytherapy was associated with good outcomes, low relapse and toxicity rates. Few events during this long-term follow-up preclude identifying specific features of patients at risk of relapse and illustrate the need for a large data-base., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: To report our experience on high-dose-rate brachytherapy (HDR-BT) in patients with stage I-III endometrial cancer unfit to surgery., Material and Methods: Seventeen patients underwent HDR-BT as definitive treatment. Median age was 79 years (range, 60-95), median Karnofsky performance status 90% (range, 60-100). Histology was endometrial adenocarcinoma in 14 (82%), and non-endometrial in 3 (18%) patients. In 15 (88%) patients, clinical stage was I and in remaining 2 (12%) was III. All patients were evaluated with computed tomography (CT) and endometrial biopsy. Using the Fletcher applicator, a CT-based planning HDR-BT was delivered. Local control (LC) was obtained when there was an interruption of vaginal bleeding in absence of CT-imaging progression., Results: Fourteen patients underwent HDR-BT alone and three external beam radiotherapy (EBRT) combined with HDR-BT. All patients had a clinical LC, after a median follow-up of 53 months (range, 6-131), 3 and 6 years LC rates were 86% and 69%, respectively. Cancer specific survival (CSS) at 1, 2, and 6 years was 93%, 85%, and 85%, respectively. Age, stage, dose, and type of radiotherapy did not result significant prognostic factors for LC and CSS. Only histology significantly influenced LC: for high-risk histology (i.e., non-endometrial carcinoma or grade [G] 3 endometrial adenocarcinoma) LC was 73% at 1 year and 36% at 6 years; for low-risk histology (i.e., G1-2 endometrial adenocarcinoma) was 100% at 1 and 6 years ( p = 0.05). Two (12%) patients had G2 acute toxicity and two others (12%) G1 late toxicity., Conclusions: Although some limitations of our analysis (relatively few number of patients recruited, retrospective evaluation, and consequent suboptimal patient selection), it confirms effectiveness and safety of definitive HDR-BT for medically inoperable stage I-III endometrial cancer. The best LC was obtained in stage I low-risk histology.

Purpose: We examined safety and efficacy of stereotactic body radiotherapy (SBRT) in reirradiation for lung recurrent lesions (LRLs)., Materials and Methods: Eighteen patients, 4 with lung local failure from primary non-small cell lung carcinomas and 14 with lung metastases, were reirradiated with SBRT for 29 LRLs. Doses were recalculated to an Equivalent Dose of 2 Gy per fraction (EQD 2 ) and α/β ratio was assumed to be Gy 10 for primary and metastatic lung tumors and Gy 3 for organ at risk. Cumulative administered doses were calculated adding doses of prior radiotherapy and reirradiation., Results: Peripherally located lesions received 5 fractions of 8-10 Gy, while centrally ones lower doses (5 fractions of 5-8 Gy). Cumulative EQD 2 did not exceed 198 Gy 10 and reirradiated volumes were rather small (median 18 cc). Local control was obtained for all patients except one and lasted medially 43 months. Median overall survival was 40 months from reirradiation. Only acute grade 1 toxicity was recorded., Conclusions: Reirradiation of LRLs with SBRT was feasible and effective. It is important to appropriately select patient and to adopt organ at risk constrains considering cumulative doses., Competing Interests: Authors’ disclosure of potential conflicts of interest The authors reported no conflict of interest.

Purpose: The aim of this work was to evaluate long-term results of moderate hypofractionated stereotactic radiotherapy (hFSRT) for intracranial meningiomas., Patients and Methods: In all, 77 consecutive patients with 80 lesions were included. Median age was 65 years (range 23-82 years), male/female ratio was 21/56, and the median Karnofsky performance status was 90 (range 60-100). In 31 lesions (39 %), diagnosis was based upon clinical and radiological data; 37 lesions were histologically proven as World Health Organization (WHO) grade I and 12 grade II meningiomas. Median treatment volume was 23 cc. Prescribed doses were 45 Gy in 15 fractions of 3 Gy (15 × 3 Gy) or 42 Gy in 14 fractions of 3 Gy (14 × 3 Gy)., Results: After a median follow-up of 56 months, 49 (61 %) lesions received 14 × 3 Gy and 31 (39 %) 15 × 3 Gy. Local control (LC) rate remained unchanged at 84 % at 5 and 10 years. Overall survival and disease-specific survival (DSS) were 76 and 93 % at 5 years, 72 and 89 % at 10 years, respectively. With univariate analysis, previous surgery and WHO grade II tumor were negative prognostic factors for LC and DSS. With multivariate analysis only tumor grade was an independent prognostic factor for LC. No clinically significant acute and/or late toxicities were observed., Conclusion: Moderate hFSRT was effective and safe with an excellent tolerance profile. It can be an alternative treatment option for patients with recurrent or inoperable large meningiomas. The low number of fractions administered with hFSRT led to reduce treatment-related discomfort for patients. Grade II tumor and previous surgery were negative prognosis factors.

Purpose: To assess the outcome of reirradiation with stereotactic radiosurgery (SRS) of brain metastases (BM) recurring after whole brain radiotherapy (WBRT)., Methods and Materials: Between September 2001 and October 2008, 69 patients who recurred after WBRT were re-irradiated with SRS using a linear accelerator. The dose prescription was generally chosen according to maximum diameter of the tumor as suggested by Radiation Therapy Oncology Group (RTOG) 90-05 protocol. Patients were stratified by Karnofsky Performance Status (KPS), Neurologic Functional Score (NFS), RTOG Recursive Partitioning Analysis (RPA), Score Index for Radiosurgery (SIR), primary disease, dimension and number of BM, and time to first brain recurrence after WBRT. Response, survival, and toxicity were analyzed., Results: At time of this retrospective analysis all patients had died. The 69 patients reirradiated with SRS had 150 metastases. Median interval between prior WBRT and SRS was 11 months and median SRS prescribed dose was 20 Gy. Response was obtained in 91% of lesions with 1-year local control rate of 74±4%. Significantly longer duration of response was associated with higher doses (≥23 Gy) and response achieved after SRS (complete and partial response better than stable disease). Cause of death was brain failure only in 36 (52%) patients. Median overall survival after reirradiation was 10 months. Variables which significantly conditioned survival were KPS and NFS. Four (6%) patients had asymptomatic radionecrosis that developed prevalently when lesion diameters were larger and cumulative doses exceeded the values recommended by RTOG 90-05 protocol. About three-fourth of the patients had a good KPS and NFS after reirradiation., Conclusions: Reirradiation of BM with SRS resulted feasible and effective. A correct patient selection and an accurate evaluation of the cumulative irradiation dose were suggested., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Purpose: Incidence, outcome and prognostic factors of metastatic spinal cord compression (MSCC) patients reirradiated for in-field recurrence were analyzed. Radiation therapists' attitude in reirradiate spinal cord relapses, doses adopted and incidence of myelopathy were also examined., Materials and Methods: Data deriving from 579 evaluable patients entered two randomized trials on radiotherapy (RT) for MSCC were revised., Results: Twenty-four (4.15%) patients had an in-field recurrence and 12 (50%) were reirradiated. At the time of analysis all reirradiated patients had died. Median time from first and second RT was 5 months (range, 2-31). Six patients received an 8 Gy single-dose, 2 patients 5×3Gy and remaining four patients 2×8, 5×4, or a single dose of 7 and 4 Gy, respectively. The median cumulative Biologically Effective Dose (BED) calculated was 114.5 Gy(2) (range, 80-120 Gy(2)). Six of seven (85.7%) ambulant patients maintained walking ability, whereas none of five not ambulant patients recovered the function. Median duration of response was 4.5 months (range, 1-24). The effect of reirradiation on motor function was significantly associated with walking capacity before reirradiation. Myelopathy was never recorded., Conclusions: In MSCC reirradiation was safe and effective. Patient walking capacity before reirradiation was the strongest prognostic factor for functional outcome. Reirradiation was given in about one-half of patients with in-field recurrence and different doses and fractionations were used, even though cumulative BED was in all cases ≤120 Gy(2)., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Aims and Background: Few clinical data exist concerning normal brain tissue tolerance to re-irradiation. The present study evaluated long-term outcome of 22 recurrent glioblastoma patients re-irradiated with radiosurgery or fractionated stereotactic radiotherapy., Methods: Twenty-two patients were treated with radiosurgery (13, 59%) or fractionated stereotactic radiotherapy (9, 41%) for 24 lesions of recurrent glioblastoma. The male/female ratio was 14:8, median age 55 years (range, 27-81), and median Karnofsky performance status 90 (range, 70-100). The majority of the cases (77%) was in recursive partitioning analysis classes III or IV Radiosurgery or fractionated stereotactic radiotherapy was chosen according to lesion size and location., Results: Median time between primary radiotherapy and re-irradiation was 9 months. Median doses were 17 Gy and 30 Gy, whereas median cumulative normalized total dose was 141 Gy and 98 Gy for radiosurgery and fractionated stereotactic radiotherapy, respectively. All patients submitted to radiosurgery had a cumulative normalized total dose of more than 100 Gy, whereas only a few (44%) of fractionated stereotactic radiotherapy patients had a cumulative normalized total dose exceeding 100 Gy. Median follow-up from re-irradiation was 54 months. At the time of analysis, all patients had died. After re-irradiation, 1 (4%) lesion was in partial remission, 16 (67%) lesions were stable, and the remaining 7 (29%) were in progression. Median duration of response was 6 months, and median survival from re-irradiation 11 months. Three of 13 (23%) patients submitted to radiosurgery developed asymptomatic brain radionecrosis. The cumulative normalized total dose for the 3 patients was 122 Gy, 124 Gy, and 141 Gy, respectively. In one case, the volume of the lesion was large (14 cc), and in the other 2 the interval between the first and second cycle of radiotherapy was short (5 months)., Conclusions: Re-irradiation with radiosurgery and fractionated stereotactic radiotherapy is feasible and effective in recurrent glioblastoma patients. Apart from the importance of an accurate patient selection, cumulative radiotherapy dose and a correct indication for radiosurgery or fractionated stereotactic radiotherapy must be taken into account to avoid brain toxicity.

Spontaneous chromosomal instability correlates with a high risk of cancer. The frequency of spontaneous sister chromatid exchanges (SCE) and micronuclei (MN) in peripheral blood lymphocytes was used for evaluation of spontaneous chromosomal instability in early-stage breast cancer patients to determine whether SCE and MN frequencies are biomarkers of damage from chemotherapy and radiotherapy. In 20 stage I-II breast cancer patients, SCE and MN were measured before surgery and at 4 weeks after. In patients who received adjuvant chemotherapy (CTx), they were also determined before starting radiotherapy (RTx). Other assessments were done 2, 6, and 12 months after RTx in almost all patients and at 18 months in 4 patients. Generalized estimating equations (GEE) were used to estimate population averaged effects at the different treatment and follow-up time points. Moreover, SCE and MN baseline values in patients were compared with those of a control group of 12 healthy women. A significant difference emerged between patients and healthy controls (P<0.0001 for SCE and P<0.0003 for MN; Mann-Whitney test); SCE increased significantly after CTx and MN increased significantly after RTx. In the GEE model, the smoking habit was associated with increased SCE in patients treated with CTx; age significantly affected MN frequencies. Both MN and SCE frequencies are increased in breast cancer patients and are indicators of CTx and RTx damage, respectively. The increased SCE levels in patients treated with CTx may be due to a synergic effect of smoking and chemotherapy.

Aims and Background: Adjuvant 5-FU chemotherapy plus radiotherapy represents the standard treatment for radically resected rectal cancer at high risk of relapse according to the NIH Consensus Conference. The therapeutic gain was obtained with a high rate of severe treatment-related toxicity and a suboptimal patient compliance with this regimen. Raltitrexed is a specific thymidylate synthase inhibitor with a convenient administration schedule, acceptable toxicity and radiosensitizing properties, as the published phase I trials in combination with radiotherapy have shown. The aim of this prospective multicenter phase II study was to evaluate the feasibility, gastrointestinal and hematological acute toxicity of raltitrexed in combination with radiotherapy in rectal cancer patients., Methods: From September 2000 to June 2004, 50 patients with radically resected stage II-III rectal adenocarcinoma were treated. All patients were evaluable for compliance and acute toxicity. Within 45-60 days of surgery, each patient underwent concomitant adjuvant radiochemotherapy. Radiotherapy was administered to the pelvis (plus perineum after abdominoperineal resection) with photon beam energy exceeding 5 MV, 3-4 fields, 45 Gy/25 fractions/5 weeks plus a boost delivered to the site of resected disease with 3-4 fields, 9 Gy/5 fractions/1 week to a total dose of 54 Gy. The boost dose was administered after complete exclusion of the small bowel from the treatment volumes; if this was not possible a total dose of 50.4 Gy was given. Raltitrexed was administered intravenously at a dose of 3 mg/m2 as a bolus injection on days 1 and 22 of radiotherapy one hour before treatment, for a total of two cycles. Each patient underwent weekly clinical evaluation and laboratory tests. Toxicity was assessed by the WHO scale., Results: Forty-five (90%) patients completed the established treatment. Acute severe toxicity included grade III proctitis in 4/50 (8%), grade III-IV diarrhea in 4/50 (8%), grade III perineal dermatitis in 4/50 (8%) and grade III leukopenia in 2/50 (4%) patients; five patients (10%) experienced a transient grade Ill increase in their liver biochemistry values., Conclusions: Our data related to acute toxicity and patient compliance proved the feasibility of this adjuvant radiochemotherapy treatment. A longer follow-up is necessary to evaluate the effectiveness of this new regimen in terms of disease-free and overall survival.

Background: The authors investigated the clinical role of tumor burden (TB) in patients with Hodgkin lymphoma, relating this parameter to most of the current clinical and prognostic factors and to the best predictive multifactorial models., Methods: The volume of TB at diagnosis was measured directly from the initial staging computed tomography scans in 351 patients who were treated on standard protocols. The mean patient age was 34.0 years +/- 16.4 years. Forty-six patients had clinical Stage I disease, 201 patients had Stage II disease, 64 patients had Stage III disease, and 40 patients had Stage IV disease. There were 146 symptomatic patients. Overall survival (OS), disease-free survival (DFS), and time to treatment failure (TTF) were the time parameters evaluated in the multivariate analysis. Logistic regression was applied according to those who achieved or failed complete remission., Results: The mean TB normalized to body surface area (rTB) was 137.8 cm(3)/m(2) +/- 124.7 cm(3)/m(2) (range, 1.9-694.5 cm(3)/m(2)). In multivariate analysis, rTB was the best predictor of TTF, DFS, and complete remission; the second best predictor of OS after patient age; and largely superior to all prognostic models analyzed. For the same stage and treatment, patients who were destined to clinical failure had an initial rTB 60-108% higher compared with the initial rTB in patients who achieved a cure, whereas differences in drug dose intensity were not significant., Conclusions: In the current study, it was found that the rTB, as a prognostic factor, was more effective than and was independent of hitherto used factors and scores. The rTB may be a tool for evaluating the curative potential of treatment combinations, allowing physicians and patients to make better therapeutic choices earlier.

Aim and Background: The aim of this study was to investigate the efficacy of postoperative locoregional radiotherapy in patients with T1-T2 breast cancer and four or more positive axillary lymph nodes submitted to mastectomy or breast-conserving surgery followed by standard-dose or high-dose adjuvant chemotherapy. The incidence of locoregional relapses and the survival correlated with the number of positive nodes were recorded for each treatment arm., Patients and Methods: From August 1992 to August 1999 86 breast cancer patients (median age, 54 years, T1-T2, N+ > or = 4) submitted to surgery were treated. Sixty-three patients received standard-dose chemotherapy while 23 patients with 10 or more positive nodes received high-dose chemotherapy. After four courses of standard-dose anthracycline-based chemotherapy peripheral blood stem cells were mobilized with cyclophosphamide (7 g/m2) and G-CSF (10-16 microg/kg/day/sc). High-dose chemotherapy consisted of etoposide 1000 mg/m2, thiotepa 500 mg/m2 and carboplatin 800 mg/m2. Hormone receptor-positive patients underwent hormone therapy. Following chemotherapy all 86 patients were given conventional radiotherapy to the breast or the chest wall and the supraclavicular fossa. The high-dose subgroup received radiotherapy to the internal mammary nodes +/- axilla., Results: The median follow-up from the start of radiotherapy was 36.5 months. Locoregional relapses occurred in nine patients (10.4%); in four of them they were isolated (4.6%). Local relapses were four (4.6%) and regional relapses six (6.9%). Twenty-five patients (29%) had distant metastases. The five-year and eight-year overall actuarial survival rates were 82.6% +/- 4.8 and 60.1% +/- 8.8, respectively. No statistical differences were found when the number of positive nodes or the type of treatment of N+ 10 patients was included in the analysis., Conclusions: Breast cancer patients with four or more positive axillary lymph nodes are at high risk of developing locoregional and distant relapses. The results reported here demonstrate the efficacy of radiotherapy in the reduction of locoregional failure; no differences in survival and locoregional control in relation to treatment arm and number of positive nodes were found.

Our purpose was to evaluate the role of MRI in distinguishing fibrous from active residual masses in treated Hodgkin's disease. Forty patients with residual mediastinal mass larger than 1.5 cm underwent MRI 1, 3, 6, and 12 months after the end of cycles of prescribed chemotherapy or combined chemoradiotherapy. The MRI examinations were performed on a 0.5 and a 1.5 T systems, using T(1) before and after gadolinium injection and T(2)-weighted sequences. Each time the residual mass was evaluated in size and signal intensity on spin echo (SE) T(2)-weighted images and on SE T(1)-weighted images after contrast medium. Low signal intensity and low contrast enhancement were considered signs of inactive residues; homogeneous high signal intensity and high contrast enhancement were indicative of active residual disease; heterogeneous signal intensity and heterogeneous contrast enhancement were indicative of partial remission or necrotic/inflammatory phenomena. MR showed high diagnostic accuracy in the evaluation of Hodgkin's mediastinal residues after treatment, if performed at least 6 months after the end of therapy, reaching the highest sensitivity and specificity values at 12 month follow-up (considering the three parameters-T(2) signal intensity, contrast-enhancement, and size-all together). If we consider the single parameters individually, we can observe that size variation remains the more valuable parameter to predict or to exclude a relapse. MR diagnostic accuracy at the 6-month follow-up was lower due to the higher incidence of inhomogeneous pattern. The accuracy of MR performed at 1 and at 3 months after the end of therapy was not satisfying. This represents a clinical problem because the most important clinical decisions have to be taken just in this early post-treatment phase.

The combination of radiation therapy CRT) and hyperthermia (HT) has proved to be an effective treatment of a wide variety of superficially located recurrences of different tumors, particularly those arising in previously irradiated areas. Some studies have been reported with the use of this combined approach in the management of cutaneous lymphomas or recurrent previously irradiated sites of Hodgkin's disease (HD). We report a small series of five patients with six located sites of recurrent HD, and four patients with six superficially located sites of non Hodgkin's lymphomas (NHL), all of them being treated with combined HT and RT at our institution. Local control was obtained in each of combined treatment fields, and all patients are alive after a median follow-up of 24 months. All the patients tolerated the HT treatments well, and in all cases average intratumoral temperatures were >42 degrees C, with 8 out of 12 sites achieving the goal of average temperatures >42.5 degrees C. Two patients, one with recurrent HD and one with NHL, are free of disease after 20 and 21 months from the end of combined therapy. Our results thus seem to confirm previous experiences, suggesting a role of HT/RT not only for palliative purposes in cutaneous lymphomas, but also in the management of selected, heavily pretreated patients with superficially located recurrences of HD.

Plasma azopigments derived from conjugated bilirubin were analyzed by thin-layer chromatography according to HEIRWEGH et al. in 14 cases of obstructive jaundice and in 11 of acute hepatitis. The chromatographic patterns were compared with those obtained from azopigments derived from 8 normal bile samples. The plasma pigment patterns did not differ from those of the bile in number and chromatographic mobility of the spots. However, the quantitative percentages of the plasma azopigments were significantly modified: the alpha 0 fraction (free azodipyrrolic pigment) increased in both icteric syndromes, while the delta fraction (mainly glucuronide azopigment) decreased. Moreover, the behavior of two closed components of the delta group showed significant differences in both icteric syndromes. It can be postulated that the synthesis of bilirubin diconjugates decreases both in hepatocellular and cholestatic jaundice, while monoglucuronidated as well as saccharide and glucoside conjugates increase. In cholestatic jaundice the conjugation with glucuronic acid mainly takes place in the normal way, whereas compounds with different features are formed in hepatitis.