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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.)

Radical cystectomy (RC) is considered the standard treatment for muscle invasive bladder cancer (MIBC). However, RC is often burdened by significant impact on quality of life (QoL); Continence preserving methods (e.g., continent cutaneous urinary diversion and orthotopic neobladder-ONB), have been proposed as alternatives to improve postoperative QoL. Trimodal therapy (TMT) emerged as alternative to surgery. To assess the impact of these treatments from the patients' perspective, we undertook a systematic review and meta-analysis of literature, focusing on studies reporting QoL data about each of the abovementioned approaches. A systematic review was carried out including all prospective and retrospective studies enrolling patientstreated with radical intent for non-metastatic MIBC from 1999 to 2021 (either RC or TMT). All studies included specifically reported QoL for one of the main treatment approaches explored (RC followed by ileal conduit urinary diversion-ICUD, ONB or TMT). Pooled analysis for EORTC QLQ-C30 and BLM-30 questionnaires showed that ONB yielded a significant advantage only for Physical Functioning (pooled mean standardized difference -0.73 SD, p-value 0.019, I 2 = 93 %) and for Emotional Functioning (pooled mean standardized difference -0.16 SD, p-value 0.029, I 2 = 0 %). A trend in favour of higher mean reported values after TMT for Global Health Score, Physical Functioning and Role Functioning was found, if compared to both RC approaches. Significant benefit for ONB if compared to ICUD was detected only for specific subdomains of QoL questionnaires. No direct comparison with TMT is available, but data suggest advantage of this approach when compared to both reconstructive scenarios., 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. Conflict of Interest IM received a small fee for occasional attendance at the advisory board supported by Lilly, Novartis, Pfizer, Seagen, Accuray which is not related to the contents of this manuscript., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) currently represent the standard of care for the initial treatment of patients with metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer. The aim of our study is to evaluate the safety of the use of concomitant radiation therapy (RT) in a consecutive series of HR+/HER2- patients treated in two academic institutions with CDK4/6i in the metastatic setting., Methods and Materials: From September 2017 to February 2020, we retrospectively collected and analysed data on a sequential series of patients treated with CDK4/6i, receiving RT or not, at two European institutions. Primary outcome of the study was the association between RT and any adverse events (AEs) ≥ G3. Secondary outcomes were the association between RT and any AEs (any grade), CDK4/6i dose reduction rate, and CDK4/6i treatment discontinuation rate., Results: We analysed a total of 132 consecutive women; RT was prescribed in 57 (43.2%) patients (70 irradiated lesions). The median age of the series was 52.1 years (range 32.3-78.2). Concomitant RT administration was not significantly related to higher AEs ≥ G3 (p = 0.19) and any grade AEs (p = 1.0); there was no association with RT and CDK4/6i dose reduction (p = 0.49) and discontinuation rates (p = 0.14). At a median follow-up of 18.8 months, the progression-free survival (PFS) rate was 35% and the overall survival (OS) rate was 38.7% in the whole group. The use of concomitant RT did not affect both PFS (p = 0.71) and OS rates (p = 0.55)., Conclusions: Our data are encouraging regarding the safety of this combination, showing that concurrent RT did not increase severe toxicity and did not have an impact on systemic treatment conduction., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background and Purpose: To report on the anti-tumor activity of a novel combination in high-risk locally advanced head and neck squamous cell carcinoma., Materials and Methods: At a fixed dose of 1500 mg every 28 days, anti PD-L1 Durvalumab was given concomitantly to Radiotherapy and Cetuximab starting from the first week of combined treatment, followed by adjuvant Durvalumab to a maximum of 6 months after completion of radiation. The primary endpoint of the study was 2-year progression-free survival (PFS). A safety run-in was planned. Due to regulatory issues which prevented from opening multiple centers, COVID-19 pandemic and withdrawal of Durvalumab from supporting company, the study was prematurely terminated in April 2021., Results: Between July 2019 and August 2020, 9 patients were enrolled in the study. All tumors had a PD-L1 Combined Positive Score > 1. Optimal drug exposure was observed, with mean relative dose intensity of 85.5% and 87.5% for Cetuximab and Durvalumab, respectively. No radiation breaks were necessary. A grade 4 mucositis lasting for 14 days corresponded to the only dose limiting toxicity we reported. At a median follow-up of 11.5 months (IQR 7.7-16.7) all surviving patients (6 out of 9) are disease-free, with 1 and 2-year PFS rates of 77.7% and 58.3%, respectively. A selective sparing of node levels in the elective volume was performed in all cases, yielding a cumulative mean dose of 37.6 Gy (SD 8.4)., Conclusion: Albeit limited by the small sample size, our preliminary observation of anti-tumor activity and tolerability of Durvalumab in addition to Cetuximab and radiation may warrant further investigations., Competing Interests: Conflicts of interest None., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: The historically feared radiation-induced secondary cancers and cardiac toxicities observed among mediastinal classical Hodgkin Lymphoma (cHL) patients may still negatively burden the benefit of radiotherapy among long-term survivors. Modern radiotherapy (RT) delivery techniques, including intensity-modulated RT (IMRT) and deep inspiration breath-hold (DIBH) solutions, are drastically changing this scenario. Results of a literature overview are reported and discussed in this paper., Materials and Methods: Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used., Results: This paper contains a narrative report and a critical discussion of organs-at-risk dose-volume metrics linked with radiation-induced toxicities in cHL patients., Conclusions: The scenario of early-stage cHL presents long-life expectancies, thus the goal of treatment should aim at maintaining high cure rates and limiting the onset of late complications. Further evaluations of dosimetric measures and clinical outcomes are warranted to identify patients at higher risk to target treatment tailoring., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Aim: Aim of this analysis is to review the role of RT in the management of several rare tumors for adult patients., Methods: Collection data regarding RT and rare tumors was made by Pubmed., Results: For mucosal melanomas, RT is prescribed, being associated with lower local recurrence rate. For trachea tumors, RT was used as adjuvant or salvage treatment for unresectable disease. For pNET, RT can be a suitable option for post-surgical or unresectable/borderline. For bronchopulmonary neuroendocrine tumors the role of adjuvant treatments is uncertain. For hepatobiliary and ovarian malignancy, stereotactic body RT (SBRT) is a promising approach. For soft tissue sarcoma, perioperative treatments are indicated, and a growing role of SBRT in oligometastatic disease is recognized. For endocrine tumors, adjuvant RT has demonstrated benefits through reducing recurrence risk., Conclusion: The radiotherapy is a frequent indication in adult rare cancers; thus the role of Radiation Oncologist must not be neglected., (Copyright © 2021 Elsevier B.V. All rights reserved.)

In case of circumscribed recurrent glioblastoma (rec-GBM), a second surgery (Re-S) and reirradiation (Re-RT) are local strategies to consider. The aim is to provide an algorithm to use in the daily clinical practice. The first step is to consider the life expectancy in order to establish whether the patient should be a candidate for active treatment. In case of a relatively good life expectancy (>3 months) and a confirmed circumscribed disease(i.e. without multiple lesions that are in different lobes/hemispheres), the next step is the assessment of the prognostic factors for local treatments. Based on the existing prognostic score systems, patients who should be excluded from local treatments may be identified; based on the validated prognostic factors, one or the other local treatment may be preferred. The last point is the estimation of expected toxicity, considering patient-related, tumor-related and treatment-related factors impacting on side effects. Lastly, patients with very good prognostic factors may be considered for receiving a combined treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Local failure (LF) following stereotactic radiosurgery (SRS) of brain metastases (BM) may be treated with a second course of SRS (SRS2), though this procedure may increase the risk of symptomatic radionecrosis (RN)., Methods: A literature search was conducted according to PRISMA to identify studies reporting LF, overall survival (OS) and RN rates following SRS2. Meta-analysis was performed to identify predictors of RN., Results: Analysis included 11 studies (335 patients,389 metastases). Pooled 1-year LF was 24 %(CI95 % 19-30 %): heterogeneity was acceptable (I2 = 21.4 %). Median pooled OS was 14 months (Confidence Interval 95 %, CI95 % 8.8-22.0 months). Cumulative crude RN rate was 13 % (95 %CI 8 %-19 %), with acceptable heterogeneity (I2 = 40.3 %). Subgroup analysis showed higher RN incidence in studies with median patient age ≥59 years (13 % [95 %CI 8 %-19 %] vs 7 %[95 %CI 3 %-12 %], p = 0.004) and lower incidence following prior Whole Brain Radiotherapy (WBRT, 19 %[95 %CI 13 %-25 %] vs 7%[95 %CI 3 %-13 %], p = 0.004)., Conclusions: SRS2 is an effective strategy for in-site recurrence of BM previously treated with SRS., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: Functional and molecular imaging, including positron emission tomography with computed tomography imaging (PET/CT) is increasing for radiotherapy (RT) definition of the target volume. This expert review summarizes existing data of functional imaging modalities and RT management, in terms of target volume delineation, for the following anatomical districts: brain (for primary and secondary tumors), head/neck and lung., Materials and Methods: A collection of available published data was made, by PubMed a search. Only original articles were carefully and critically revised., Results: For primary and secondary brain tumors, amino acid PET radiotracers could be useful to identify microscopic residual areas and to differ between recurrence and treatment-related alterations in case of re-irradiation. As for head and neck neoplasms may benefit from precise PET/CT-based target delineation, due to the major capability to identify high-risk RT areas. In primary and secondary lung cancer, PET/CT could be useful both to delimit a tumor and collapsed lungs and as a predictive parameter of treatment response., Conclusion: Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic care going forward. Nevertheless, several uncertainties remain on the standard method to properly assess the target volume definition including PET information for primary and secondary brain tumors., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: Positron Emission Tomography with Computed Tomography (PET/CT) has been proven to be useful in the definition of Radiotherapy (RT) target volume. In this regard, the present expert review summarizes existing data for pancreas, prostate, gynecological and rectum/anal cancer., Methods: A comprehensive search of published original article was made, based on SCOPUS and PubMed database, selecting the paper that evaluated the role of PET/CT in the definition of RT volume., Results: FDG-PET has an important and promising role for pancreatic cancer. Choline PET/CT could be useful for identifying high-risk volumes for prostate cancer; while PSMA PET/CT is still under evaluation. FDG PET/CT in gynecological cancers has been shown to impact external-beam RT planning. The role of FDG-PET for Gross Tumor volume identification is crucial, representing a useful and powerful tool for anal and rectal cancer., Conclusion: Taken together, molecular and functional imaging approaches offer a major step to individualize radiotherapeutic approach., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A diagnosis of breast cancer at a young age, defined per guidelines as ≤ 40 years, represents a challenging situation requiring additional attention by the treating physicians including radiation oncologists and surgeons involved in the local treatment of these tumors. The present review aims at providing updated evidence on the state of the art about the available techniques and indications for radiation therapy in patients with early breast cancer, specifically focusing on young women. In addition, future perspectives including the ongoing trials and the potential impact of combined approaches with systemic therapies (such as immunotherapy) are reviewed. Major conclusions from this overview are that young women affected by invasive breast cancer seem to receive the greatest benefit from the boost on the tumor bed. Most young patients affected by ductal carcinoma in situ should receive postoperative whole breast irradiation (WBI). When regional node irradiation is considered, young age should be considered as a high-risk factor. Partial breast irradiation is not suitable for young patients and should be recommended within the context of a clinical trial. Importantly, robust data have already supported the efficacy and safety of hypofractionated-WBI schedules that should now replace standard fractionated-WBI as gold standard for all patients irrespective of their age. Finally, organs-at-risk sparing systems as strategy for prevention of radiation-related long-term toxicities should be strongly considered for these patients. Considering the lack of inclusion of young patients in several published trials as well as in some of the ongoing ones, robust evidence to counsel young breast cancer patients on the optimal radiation therapy approach is still lacking. Further studies and ad hoc subgroup analyses in this specific patient population are strongly warranted., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Purpose: Breast-conserving surgery (BCS) and whole breast radiation (RT) with or without endocrine therapy (ET) represent the standard of care for ductal carcinoma in situ (DCIS). The use of adjuvant treatments after surgery is still controversial in this setting. We performed a retrospective multicenter analysis on a series of DCIS patients treated with BCS and adjuvant RT., Materials and Methods: We collected clinical data from nine Italian centers on 1072 women having a diagnosis of DCIS and treated between 1997 and 2012. We reported on the 5- and 10-year local recurrence (LR) rates, overall survival, and breast cancer specific survival (BCSS) employing the Kaplan-Meier method., Results: At a median follow-up of 8.4 years, 67 LR (6.3%) and 47 deaths (4.4%) were observed. LR rates at 5 and 10 years were 3.4% and 7.6%, respectively. BCSS rates at 5 and 10 years were 99.7% and 99.1%, respectively. At univariate regression analysis, postmenopausal state (p = 0.009), estrogen receptor (ER) (p = 0.0001) and progesterone receptor (p = 0.018) positivity and ET (p = 0.006) were inversely correlated with LR. Final surgical margins (FSM) status <1 mm was significantly correlated with higher LR (p = 0.003). At multivariate regression analysis postmenopausal state (p = 0.03), and ER positive (p = 0.045) maintained the significant favorable feature, while FSM <1 mm (p = 0.024) confirmed its negative impact on LR., Conclusions: Our real-life study pointed out the significant favorable prognostic role of postmenopausal state and ER positive status on LR occurrence. FSM <1 mm was significantly correlated to a higher chance to experience LR., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Purpose: Aim of the present review is to assess present data about the use of the association of Radiotherapy (RT) and targeted therapy/immunotherapy (TT/IT) in elderly people., Design: PubMed database was searched for English literature published up to December 2017 using the keywords "radiotherapy" combined with "bevacizumab", "cetuximab", "trastuzumab", "erlotinib", "gefitinib", "sorafenib", "sunitinib", "vismodegib", "sonidegib", "ipilimumab", "pembrolizumab", "nivolumab". Studies performing RT and TT/IT in people aged >65-years were evaluated focusing on safety, toxicity and efficacy. Studies eligible for inclusion were: case reports, retrospective/prospective studies in which RT and new drugs were used concomitantly or sequentially, focusing on elderly sub-group., Results: The systematic search identified 626 records. After exclusion of duplicates, full-text review, cross-referencing and paper that did not respect the inclusion criteria, 81 studies were included in this review. In elderly patients the combination of RT with cetuximab or bevacizumab seems feasible but with higher reported side effects. Patients' age should not limit the association of trastuzumab and RT in HER2 positive breast cancer. The concurrent administration of TKIs and RT appears to be feasible and effective. Regarding the Immune Check Point inhibitors and RT, tolerance seems similar among older and younger people but definitive data are lacking. Instead, the association of RT and vismodegib/sonidegib remains investigational., Conclusion: TT/IT in association of RT seems to be safe, but in elderly patients data concerning safety and toxicity are limited. Specific clinical trials on this population are encouraged., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Stereotactic body radiotherapy (SBRT) is characterized by the delivery of high doses of ionizing radiation in few fractions. It is highly effective in achieving local control, and, due to the high biological effective dose administered, it seems to overcome the radioresistance of renal cell carcinoma (RCC). Thus, SBRT could constitute a treatment option for the management of localized RCC in patients who are not surgical candidates. In this paper, we report an overview about data from the current evidence about SBRT in patients affected by localized RCC., Materials and Methods: A non-systematic review was performed, including data from both retrospective and prospective studies focusing on the use of SBRT for localized RCC and its biological rationale. Furthermore, ongoing trials on this issue are reported., Conclusion: Currently, SBRT might be considered a treatment alternative in inoperable patients affected by primary RCC. Currently, dose-escalation to 48 Gy in 3-4 fractions are effective and well tolerated. Emerging role of immune therapies in RCC patients warrant further studies to explore interactions between SBRT and immune response., (Copyright © 2018 Elsevier B.V. All rights reserved.)

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.)

Background and Purpose: There is currently no health-related quality of life (HRQoL) measure specific to anal cancer. Our objective was to develop an anal cancer HRQoL module to supplement the EORTC QLQ-C30 questionnaire using EORTC Quality of Life Group Guidelines., Materials and Method: In order to generate a list of HRQoL issues facing anal cancer patients treated with chemoradiotherapy (CRT), we systematically reviewed the literature and conducted semi-structured interviews with patients and health care professionals (HCPs). Our list was then operationalised into questions using the EORTC Item Library. The provisional question list was pilot tested alongside the EORTC QLQ-C30 with patients from 11 centres across 8 countries., Results: From our literature review and interviews with 43 patients, we generated a list of 197 issues. The list was then refined to 134 issues and reviewed by 34 HCPs and 10 patients. This review resulted in the retention of 65 issues which were used in the draft questionnaire tested by 100 patients. Our analyses led to the modification and removal of questions resulting in a 27 item questionnaire, the EORTC QLQ-ANL27., Conclusion: We have developed a 27 item questionnaire to supplement the EORTC QLQ-C30, for use with patients treated for anal cancer. This has been pilot tested and is now available upon request for use in clinical trials as well as clinical practice in 8 languages (http://groups.eortc.be/qol/)., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Radiotherapy plus cetuximab is an effective combination therapy for locally advanced head and neck squamous cell carcinoma. The aim of our study was to determine the frequency of skin toxicity in patients receiving the combined treatment., Results: Forty-eight studies were included in our analysis, for a total of 2152 patients. The mean rates of G3/G4 radiation dermatitis and acneiform rash were 32.5% (SD: 20.4; 95% CI: 28.5-36.5) and 13.4% (SD: 11.5; 95% CI: 11.2-15.6), respectively. The majority of studies referred to CTCAE scales for reporting both side effects (85.7% and 92.1%, respectively). Data on the management of skin toxicity were available in only 35.4% of the reviewed literature., Conclusions: severe radiation dermatitis is a frequent side effect induced by the combination of radiotherapy and cetuximab in head and neck cancer. The lack of predictive biomarkers of toxicity hampers the possibilty to design preventive measures on a personalized basis., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Major advances in the knowledge of cancer biology and its interactions with tumor immune environment led to the emergence, in the last five years of new immunotherapy-based treatment strategies in cancer patients. At the same time, improvement in radiation technique and progress in radiobiology allowed in the last decade to expand the applications of radiotherapy in a growing number of settings. At present, there are strong theoretical basis to propose immune-enhanced radiation therapy that may represent in the future a new paradigm of treatment, combining the intrinsic power of radiotherapy to elicit a specific, systemic, tumor-directed immune response with modern highly conformal and precise dose delivery, in order to maximize response at the major site of disease and obtain durable disease control. The aim of this review is to describe the principal mechanisms of immune modulation of response to radiation and investigational strategies to harness the potential of radiation-inducible immune response: radiation therapy is expected to be not just a local treatment but the cornerstone of a multimodal strategy that might achieve long-lasting tumor remission at the primary site and systemic efficacy metastatic lesions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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.)