Search

Simple Summary: This article is a report about early toxicity and biochemical outcomes after stereotactic salvage radiotherapy for macroscopic recurrence within prostate bed after radical prostatectomy. Data reported suggest optimal tolerability profile and promising oncologic outcomes after this approach within a prospective multicentric trial. Biochemical recurrences after radical prostatectomy (RP) can be managed with curative purpose through salvage radiation therapy (SRT). RT dose escalation, such as stereotactic RT (SSRT), may improve relapse-free survival in this setting. STARR trial (NCT05455736) is a prospective multicenter study including patients affected by macroscopic recurrence within the prostate bed after RP treated with SSRT. Recurrence was detected with a Choline or PSMA CT-PET. In the current analysis, the early biochemical response (BR) rate and toxicity profile after three months of follow-up were assessed. Twenty-five patients were enrolled, and data about BR and toxicity at three months after treatment were available for 19 cases. Overall, BR was detected after three months in 58% of cases. Four G1–G2 adverse events were recorded; no G ≥ 3 adverse events were detected. SSRT appears feasible and safe, with more than half of patients experiencing BR and an encouraging toxicity profile. The STARR trial is one of the few prospective studies aimed at implementing this promising treatment strategy in this scenario. [ABSTRACT FROM AUTHOR]

Simple Summary: This paper aims at showing the impact of novel imaging technologies and modern radiotherapy techniques on the management of cancer, with a particular focus on prostate adenocarcinoma. The manuscript explores the value of diagnostic imaging before treatment, the role of radiomics in predicting outcomes, the benefit of novel imaging in radiotherapy planning and the influence of advanced technologies in systemic treatment and in the management of other non-oncological conditions in order to tailor the best therapeutical strategies. Introduction: Targeted dose-escalation and reduction of dose to adjacent organs at risk have been the main goal of radiotherapy in the last decade. Prostate cancer benefited the most from this process. In recent years, the development of Intensity Modulated Radiation Therapy (IMRT) and Stereotactic Body Radiotherapy (SBRT) radically changed clinical practice, also thanks to the availability of modern imaging techniques. The aim of this paper is to explore the relationship between diagnostic imaging and prostate cancer radiotherapy techniques. Materials and Methods: Aiming to provide an overview of the integration between modern imaging and radiotherapy techniques, we performed a non-systematic search of papers exploring the predictive value of imaging before treatment, the role of radiomics in predicting treatment outcomes, implementation of novel imaging in RT planning and influence of imaging integration on use of RT in current clinical practice. Three independent authors (GF, IM and ID) performed an independent review focusing on these issues. Key references were derived from a PubMed query. Hand searching and clinicaltrials.gov were also used, and grey literature was searched for further papers of interest. The final choice of papers included was discussed between all co-authors. Results: This paper contains a narrative report and a critical discussion of the role of new modern techniques in predicting outcomes before treatment, in radiotherapy planning and in the integration with systemic therapy in the management of prostate cancer. Also, the role of radiomics in a tailored treatment approach is explored. Conclusions: Integration between diagnostic imaging and radiotherapy is of great importance for the modern treatment of prostate cancer. Future clinical trials should be aimed at exploring the real clinical benefit of complex workflows in clinical practice. [ABSTRACT FROM AUTHOR]

• Significant benefit for ONB if compared to ICUD was detected only for specific subdomains of QoL questionnaires. • No direct comparison between ICUD/ONB and TMT is available. • These data should be used in clinical practice to empower patients in deciding about local treatment choice. 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 patients treated 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. [ABSTRACT FROM AUTHOR]

Historically, non-seminomatous germ cell tumor (NSGCT) has been considered a radio-resistant disease, excluding radiotherapy (RT) from curative strategies. However, case series exploring the use of radiation treatment in this setting are often outdated, and prospective ongoing studies testing new radiotherapeutic approaches in NSGCT are lacking. Considering that tremendous advances in radiotherapy technology have enabled improved precision in RT delivery as well as dose escalation while decreasing treatment-related morbidity, we overviewed the currently available literature to explore the radiobiological basis, the technical issues, and potential strategies for implementation of RT in the management of this clinical entity. The purpose of the present overview is to provide insight for future research in this unexplored scenario. In summary, the biological rationale for RT use and potential implementation with systemic therapies exist, especially considering the advantage of new technologies, which were unavailable in the era of early literature reports. The NSGCT radioresistance paradigm could be based only on the fact that effective treatment schedules were simply undeliverable with older RT techniques due to toxicity issues, but the availability of actual techniques may prompt further exploration to offer treatment alternatives to these patients. Ongoing trials on this issue are lacking, but potential areas of research are platinum-refractory disease and consolidation therapy for residual masses after PST. [ABSTRACT FROM AUTHOR]

New metabolic tracers have improved sensitivity and specificity for the real extent of tumor burden in prostate cancer. This study aims to compare the impact of these tracers for metastasis-directed therapy. Gallium-68 prostate-specific membrane antigen-positron emission tomography-guided metastasis-directed therapy in castration-sensitive oligorecurrent prostate cancer patients resulted in higher rates of androgen deprivation therapy-free survival, when compared with 18F-fluorocholine positron emission tomography-guided treatments (P = .00). Background: The present analysis aims to compare the impact of 18F-fluorocholine (18F-choline) and gallium-68 prostatespecific membrane antigen (68Ga-PSMA) positron emission tomography (PET)-computed tomography (CT)eguided metastases-directed therapies (MDTs) in patients with castration-sensitive oligorecurrent prostate cancer (PC). Materials and Methods: Inclusion criteria were: (1) histologically proven prostate adenocarcinoma; (2) evidence of biochemical relapse after primary tumor treatment; (3) ≤ 3 hypermetabolic oligorecurrent lesions detected by 18F-choline or 68Ga-PSMA PET-CT; (4) PET-CT imaging performed in a single nuclear medicine department; (5) patients treated with upfront stereotactic body radiotherapy (SBRT) without hormone therapy; and (6) SBRT delivered with a dose per fraction ≥ 5 Gy. In the case of oligoprogression (≤ 3 lesions outside the previous RT field) after MTD, a further course of SBRT was proposed; otherwise, androgen deprivation therapy (ADT) was administered. Results: A total of 118 lesions in 88 patients were analyzed. Forty-four (50%) patients underwent 68Ga-PSMA PET-guided SBRT, and the remaining underwent choline PET-based SBRT. The median follow-up was 25 months (range, 5-87 months) for the entire cohort. Overall survival and local control were both 100%. Distant progression occurred in 48 (54.5%) patients, for a median distant progression-free survival of 22.8 months (range, 14.4-28.8 months). The median pre-SBRT prostate-specific antigen was 2.04 ng/mL in the choline PET cohort and 0.58 ng/mL in the PSMA-PET arm. Disease-free survival rates were 63.6% and 34%, respectively, in the 68Ga-PSMA and choline PET group (P = .06). The ADT administration rate was higher after choline-PETeguided SBRT (P = .00) owing to the higher incidence of polymetastatic disease after first-course SBRT compared with 68Ga-PSMA-based SBRT. Conclusion: In the setting of oligorecurrent castration-sensitive PC, PSMA-PET-guided SBRT produced a higher rate of ADT-free patients when compared with the 18F-choline-PET cohort. Randomized trials are advocated. [ABSTRACT FROM AUTHOR]

Objective: To assess the safety and effectiveness of stereotactic salvage radiotherapy (SSRT) in RT‐naïve patients affected by macroscopic prostate bed recurrence. Patients and methods: Consecutive patients treated for prostate bed macroscopic recurrence in three different Italian institutes were reviewed. Patients were treated with SSRT, with a total dose of 30–40 Gy in five fractions, the mean pre‐SSRT PSA level was 2.3 ng/mL. Two different PSA thresholds were defined and biochemical recurrence‐free survival (BCRFS) was reported, in order to better express outcome: BCRFS1 (a PSA level increase of >10% compared to the pre‐SSRT value) and BCRFS2 (a PSA level increase of >0.2 ng/mL for patients with a PSA nadir of <0.2 ng/mL or two consecutive PSA level increases of >25% compared to nadir in patients with a PSA nadir of <0.2 ng/mL). Results: In all, 90 patients were treated, with a mean (range) follow‐up of 21.2 (2–64) months, and 17 of these patients (19%) had concomitant androgen‐deprivation therapy (ADT) during SSRT. Complete biochemical response, defined as a PSA nadir of <0.2 ng/mL, was obtained in 39 of the 90 patients (43.3%). Considering BCRFS1, 25 patients (27.8%) had BCR, with an actuarial median BCRFS1 time of 36.4 months. For BCRFS2, BCR was reported in 32 patients (35.5%), with an actuarial median BCRFS2 time of 24.3 months. There was no Grade >2 toxicity. Conclusions: SSRT was found to yield significant biochemical control and allowed ADT delay despite adverse features. [ABSTRACT FROM AUTHOR]

• Ablative radiotherapy is an effective treatment for oligometastatic prostate cancer. • The lack of randomized phase III trials hampers the generalization of this therapy. • In clinical practice, ablative radiotherapy should be adopted in some cases only. • This position paper explores available literature and proposes some recommendations. Oligometastatic prostate cancer comprises a wide spectrum of conditions, ranging from de novo oligometastatic cancer at diagnosis to oligometastatic castration-resistant disease, which are distinct entities in terms of biology and prognosis. In order to clarify and standardize the clinical role of ablative radiotherapy in oligometastatic prostate cancer, the Italian Association of Radiotherapy and Clinical Oncology (AIRO) formed an expert panel to review the current literature and develop a formal consensus. Oligometastatic prostate cancer was defined as the presence of up to three metastatic lesions involving bones or nodes outside pelvis. Thereafter, four clinical scenarios were explored: metastatic castration-sensitive disease at diagnosis and after primary treatment, and metastatic castration-resistant disease at diagnosis and during treatment, where the role of ablative radiotherapy was defined either in conjunction with systemic therapy or as the only treatment in selected cases. This paper summarizes the current literature about these issues and the proposed recommendations. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Aims: Re-irradiation with stereotactic body RT (re-SBRT) is a valid treatment option for local relapse in prostate cancer after postoperative or definitive radiotherapy (RT). However, we need predictive factors to prevent the onset of late adverse events. Here we present a retrospective analysis conducted on a cohort of patients treated with re-SBRT through Cyberknife ® robotic system. The correlation between dosimetric data and incidence of late genitourinary (GU) toxicity was evaluated to establish a model to predict late GU Grade >2 adverse events in this population. Methods: We collected data of 50 consecutively patients treated from June 2012 to February 2016. All patients were affected by biochemical relapse defined by European Urology Association Criteria after definitive or postoperative radiotherapy, and macroscopic evidence of intra-prostatic or prostate bed recurrence was detected by 18F-choline PET/CT and MRI. Patients with metastatic or regional nodal disease were excluded. All patients underwent reSBRT using the CyberKnife ®robotic system, for a total dose of 30 Gy in 5 fractions every other day. Toxicity was assessed by the Common Terminology Criteria for Adverse Events (CTCAE) toxicity scale v.5. Relationship between late GU G>2 and Gross Target Volume (ccGTV), Dose to 50% of urinary bladder volume (DB50), Maximum dose within Planning Target Volume (Dmax), urethra Dmax (UDmax) and Total Equivalent Dose (tEQD2) administered to prostate or prostate bed was explored with logistic regression. A receiver operating characteristic (ROC) curve was used to find the optimal cut-off point for continuous variables significantly predictive for late GU adverse events. Results: After a median follow up of 48.2 months (6.4-86.3), late G> 2 GU toxicity occurred in 13 (26%) patients. At Univariate Analysis, no significant impact of ccGTV (p=0.38), DB50 (p=0.25), Dmax (p=0.88), and tEQD2 total was detected (p=0.76 ). Only UDmax showed significant association with Late G> 2 GU toxicity (p=0.02). ROC analysis showed that UDmax >34.12 Gy best predicted GU toxicity, with a positive and negative likelihood ratio of 3.56 (95% CI 1.1-11.3) and 0.69 (95% CI 0.4-1.1), respectively (AUC 0.66, p=0.06). Conclusion: These data suggest that higher urethral dose may be associated to higher risk of late G> 2 GU toxicity. Thus, due to the low number of events, larger series with long term follow up would be needed to better identify a model to predict late GU adverse events after re-SBRT. [ABSTRACT FROM AUTHOR]

Background and purpose To report on a Quality assessment (QA) of Skagen Trial 1, exploring hypofractionation for breast cancer patients with indication for regional nodal radiotherapy. Material and methods Deviations from protocol regarding target volume delineations and dose parameters (Dmin, Dmax, D98%, D95% and D2%) from randomly selected dose plans were assessed. Target volume delineation according to ESTRO guidelines was obtained through atlas based automated segmentation and centrally approved as gold standard (GS). Dice similarity scores (DSC) with original delineations were measured. Dose parameters measured in the two delineations were reported to assess their dosimetric outcome. Results Assessment included 88 plans from 12 centres in 4 countries. DSC showed high agreement in contouring, 99% and 96% of the patients had a complete delineation of target volumes and organs at risk. No deviations in the dosimetric outcome were found in 76% of the patients, 82% and 95% of the patients had successful coverage of breast/chestwall and CTVn_L2-4-interpectoral. Dosimetric outcomes of original delineation and GS were comparable. Conclusions QA showed high protocol compliance and adequate dose coverage in most patients. Inter-observer variability in contouring was low. Dose parameters were in harmony with protocol regardless original or GS segmentation. [ABSTRACT FROM AUTHOR]

• A systematic review of studies comparing TMT and RC for MIBC patients was performed. • Qualitative and quantitative evaluation of outcomes was performed with GRADE system. • A final weak positive recommendation in favour of TMT versus RC was developed. To compare trimodality therapy (TMT) versus radical cystectomy (RC) and develop GRADE (Grades of Recommendation, Assessment, Development and Evaluation) Recommendation by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) for treatment of muscle-invasive bladder cancer (MIBC). Prospective and retrospective studies comparing TMT and RC for MIBC patients were included. Qualitative and quantitative evaluation of evidence was made. Ten studies were included in the analysis. Pooled analysis showed salvage cystectomy and pathological complete response rates after TMT of 12 % and 72–77.5 %, respectively. Pooled rates of G3-G4 GU toxicity and serious toxicity rate were 18 vs 3% and 45 vs 29 % for patients undergoing TMT vs RC, respectively. The panel assessed a substantial equivalence in terms of OS and CSS at 5 years between TMT and RC. TMT could be suggested as an alternative treatment to RC in non-metastatic MIBC patients, deemed fit for surgery. [ABSTRACT FROM AUTHOR]

Sexual function can be impaired by all prostate cancer treatment modalities, but studies specifically addressing the impact of stereotactic body radiotherapy (SBRT) on sexual function are scarce. To systematically evaluate sexual outcomes in patients treated by SBRT for prostate cancer and determine clinical factors associated with erectile dysfunction (ED). A systematic review of the available literature was performed on PubMed/Medline, Scopus, and Cochrane Library databases in June 2017 according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Only articles providing data on baseline and post-treatment sexual function after SBRT (≥5 Gy/fraction) were included in this analysis (n = 12). Sexual function deteriorates after SBRT of the prostate. Deterioration of sexual health was found, with Expanded Prostate Cancer Index Composite–26 sexual domain scores showing a median decrease of 9.2 at 12 months and a median decrease of the Sexual Health Inventory for Men subdomain score by 2.7 at 12 months (from baseline median value of 56.3 and 16, respectively). At 60 months, ED was reported by 26–55% of previously sexually functioning patients in 5 of the 12 studies. ED affects ≤55% of previously sexually functioning patients at 5 years, as reported for other non-surgical treatment modalities. This study enforced strict inclusion criteria of selected studies and exclusion of patients receiving concurrent androgen deprivation therapy. However, inconsistencies in the choice of assessment tool and definition of ED hamper a robust meta-analysis of pooled data. Sexual function decline after SBRT for prostate cancer appears to be similar to other modalities and should be specifically addressed in future studies. Loi M, Wortel RC, Francolini G, et al. Sexual Function in Patients Treated With Stereotactic Radiotherapy For Prostate Cancer: A Systematic Review of the Current Evidence. J Sex Med 2019;16:1409–1420. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Trabectedin is used for the treatment of advanced soft tissue sarcomas (STSs). In this study, we evaluated if trabectedin could enhance the efficacy of irradiation (IR) by increasing the intrinsic cell radiosensitivity and modulating tumor micro-environment in fibrosarcoma (HS 93.T), leiomyosarcoma (HS5.T), liposarcoma (SW872), and rhabdomyosarcoma (RD) cell lines. A significant reduction in cell surviving fraction (SF) following trabectedin + IR compared to IR alone was observed in liposarcoma and leiomyosarcoma (enhancement ratio at 50%, ER50: 1.45 and 2.35, respectively), whereas an additive effect was shown in rhabdomyosarcoma and fibrosarcoma. Invasive cells' fraction significantly decreased following trabectedin ± IR compared to IR alone. Differences in cell cycle distribution were observed in leiomyosarcoma and rhabdomyosarcoma treated with trabectedin + IR. In all STS lines, trabectedin + IR resulted in a significantly higher number of γ-H2AX (histone H2AX) foci 30 min compared to the control, trabectedin, or IR alone. Expression of ATM, RAD50, Ang-2, VEGF, and PD-L1 was not significantly altered following trabectedin + IR. In conclusion, trabectedin radiosensitizes STS cells by affecting SF (particularly in leiomyosarcoma and liposarcoma), invasiveness, cell cycle distribution, and γ-H2AX foci formation. Conversely, no synergistic effect was observed on DNA damage repair, neoangiogenesis, and immune system. [ABSTRACT FROM AUTHOR]

Loco-regional recurrence (LRR) is the predominant pattern of failure in locally-advanced head and neck cancer (HNC), both in squamous cell carcinoma (SCC) and non-squamous histotypes. Despite the proven role of radiotherapy (RT) as primary treatment strategy, there is sparse evidence on the use of reirradiation (ReRT) in recurrent HNC (rHNC). Various regimens of hypofractionation have been described in the literature, without a clear consensus. The aim of our single-centre study is to evaluate the clinical outcome of unresectable rHNC patients treated with Cyberknife-based (CK) hypofractionated reRT. We retrospectively analyzed data from consecutive patients with rHNC who received CK reRT at our institution. All eligible patients had a recurrent, non-metastatic, previously irradiated unresectable HNC. Each case was discussed at a multidisciplinary level before treatment. Local control (LC), progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method and log rank test with time measured from the date of last day of reRT to date of local recurrence, progression of disease or death, respectively. [Display omitted] First curatively intended course of RT was delivered from 1997 to 2020, concomitantly with chemotherapy or not. Thirty-five patients received Cyberknife (CK)-based hypofractionated reRT. The majority of patients (22, 63%) had a diagnosis of SCC and 13 patients (37%) had other histotypes than SCC. The median age of the cohort was 62 years at diagnosis. The CK reRT was performed from 2012 to 2022. The most commonly adopted schedules of reRT were 25Gy (57%) and 30Gy (43%) in 5 fractions on alternating days. After a median follow-up of 12 months (range 2-48), 6 out of 35 patients were alive. Causes of death were related to HNC in 12 patients and in 9 to other causes. The median LC and the 1-year LC rate were 10 months (95% CI 6,6-13,4 months) and 42%, respectively. The median PFS and OS and the 1-year PFS and OS rates were 8 months (95% CI 6.1-9,8 months), 18 months (95% CI 11,8-24,1 months) and 15% and 71% (Figure 1), respectively. At univariate analysis, a negative correlation between time to CK reRT < 12 months and LC (p 0.01) was reported. Moreover, a positive trend association between time from first to second irradiation ≥ 12 months and OS (p 0.09) was shown, in line with findings available from the literature. A significantly better OS was found in patients aged < 65 years (p 0.045). From our analysis, hypofractionated ReRT can be viewed as a well-tolerated treatment option for rHNC with potential for prolonged local control in appropriately selected patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Cigarette smoking increases the risk of developing bladder cancer; many of these patients are active smokers at diagnosis. There is evidence that smokers with cancer at other sites (e.g., lung) may improve their chance of surviving if they stop smoking upon diagnosis. However, similar evidence is still lacking for bladder cancer. Here, we reviewed the scientific literature up to January 2022 but found a mere nine articles focusing on this topic, which provided insufficient evidence to draw firm conclusions. While more research is urgently needed, bladder cancer patients who are still smoking at diagnosis should receive information on the multiple health benefits of smoking cessation and all the support they need to stop successfully. We reviewed the studies examining whether quitting smoking at or around diagnosis favourably affects the prognosis of bladder cancer (BC) patients, who are often active smokers at diagnosis. We found only nine eligible articles published until 31 January 2022, which encompassed around 5500 BC in total, the majority of which were nonmuscle invasive BC (only one paper included muscle-invasive BC). We used random effects meta-analysis to obtain a summary hazard ratio (SHR) and 95% confidence intervals (CI). The median proportion of smokers who quit at or around diagnosis was 29.8% (range 8.4–43.1%). For the overall, BC-specific, and progression-free survival, the studies were limited in number (n = 3) and provided conflicting results. At the same time, quitters did not appear to have a lower risk of recurrence than continued smokers (SHR 0.99, 95% CI 0.61–1.61). In conclusion, while the evidence is currently not sufficient to draw firm conclusions (especially for patients with muscle-invasive BC), physicians should not refrain from educating smoking BC patients about the benefits of smoking cessation and provide the necessary support. [ABSTRACT FROM AUTHOR]

Metastatic hormone-sensitive prostate cancer (mHSPC) is usually categorized as high- or low-volume disease. This is relevant because low- and high-volume metastatic disease are associated with different outcomes, and thus management of the two forms should differ. Although some definitions have been reported, the concept of oligometastatic disease is not so clearly defined, giving rise to further variability in the choice of treatment, mainly between systemic agents and radiotherapy, especially in the era of metastasis-directed therapy. With the aim of providing clinicians with guidance on best practice, a group of medical and radiation oncologists, experts in prostate cancer, used the round robin method to generate a series of consensus statements on management of low-volume mHSPC. Consensus was obtained on three major areas of controversy: (1) with regard to clinical definitions of mHSPC, it was held that oligometastatic and low-volume disease refer to different concepts and should not be used interchangeably; (2) regarding therapy of de novo low-volume metastatic disease, androgen deprivation therapy alone can be considered undertreatment, and all patients should be evaluated for systemic treatment combinations; local therapy should not be denied in patients with mHSPC, regardless of the intensity of systemic therapy, and metastasis-directed therapy can be proposed in selected cases; (3) with regard to treatment of metachronous metastatic disease, patients should be evaluated for systemic treatment combinations. Metastasis-directed therapy can be proposed to delay systemic treatment in selected cases, especially if prostate-specific membrane antigen positron emission tomography staging has been performed and when indolent disease occurs. It is hoped that clinicians treating patients with mHSPC in daily practice will find this expert opinion of value. [ABSTRACT FROM AUTHOR]

• Tyrosine Kinases Inhibitors were used in combination with SBRT in 93% of cases. • Radiotherapy schedules of single fraction doses were 10–20 Gy. • Radiotherapy schedules of hypofractionated doses were 35–60 Gy in 3–5 fractions. • Local control of irradiated lesions was achieved in 76–100% of the patients. • The 2-year overall survival was 71% after combined approach. To conduct a systematic review and meta-analysis of the role of SBRTdrug combination in patients affected by mRCC and associated oncologic outcomes and toxicity profiles. We performed a critical review of the Pubmed, Medline, and Embase databases from January 1, 2000 through April 30, 2020 according to the Preferred Reporting Items and Meta-Analyses statement. To assess the overall quality of the literature reviewed, we used a modified Delphi tool. A total of 6 studies were included, corresponding to a cohort of 216 patients. Tyrosine Kinases Inhibitors were the most widely used drugs in combination with SBRT, being administered in 93% patients. No study reported an increase of radiation-induced toxicity. SBRT resulted to be safe, without increase in terms of drugs-related adverse events in this setting. Moreover, this approach showed promising clinical outcomes in terms of LC and OS [ABSTRACT FROM AUTHOR]

Purpose: Herein, we report the clinical outcomes of a multicenter study evaluating the role of SBRT in a cohort of patients affected by oligoprogressive castration-resistant prostate cancer (CRPC). Materials and methods: This is a retrospective multicenter observational study including eleven centers. Inclusion criteria of the current study were: (a) Karnofsky performance status > 80, (b) histologically proven diagnosis of PC, (c) 1–5 oligoprogressive metastases, defined as progressive disease at bone or nodes levels (detected by means of choline PET/CT or CT plus bone scan) during ADT, (d) serum testosterone level under 50 ng/ml during ADT, (e) controlled primary tumor, (f) patients treated with SBRT with a dose of at least 5 Gy per fraction to a biologically effective dose (BED) of at least 80 Gy using an alpha-to-beta ratio of 3 Gy, (g) at least 6 months of follow-up post-SBRT. Results: Eighty-six patients for a total of 117 lesions were treated with SBRT. The median follow-up was 30.7 months (range 4–91 months). The median new metastasis-free survival after SBRT was 12.3 months (95% CI 5.5–19.1 months). One- and two-year distant progression-free survival was 52.3% and 33.7%, respectively. Twenty-six out of 86 patients underwent a second course of SBRT due to further oligoprogressive disease: This resulted in a median systemic treatment-free survival of 21.8 months (95% CI 17.8–25.8 months). One-year systemic treatment-free survival was 72.1%. Conclusion: SBRT appears to be a promising approach in oligoprogressive castration-resistant prostate cancer. Further investigations are warranted. [ABSTRACT FROM AUTHOR]

The standard of care for early-stage breast cancer (BC) consists of breast-conserving surgery followed by postoperative irradiation. Recently, the concept of changing the usual sequence of treatment components in BC RT has been investigated. Potential advantages of preoperative RT in BC include a possible tumor downstaging with improved surgical cosmetic outcomes, accurate tumor site identification and better target volume delineation. Furthermore, preoperative RT could serve as a tool for treatment stratification for de-escalation of treatments in the event of pathological complete response. The present literature review analyzed the available clinical data regarding the potential impact of preoperative RT. Overall, available clinical evidence of preoperative RT in BC remains limited, deriving mostly from retrospective case series. Nevertheless, the experiences prove the feasibility of the preoperative RT approach and confirm the efficacy in almost all analyzed studies, including experiences using higher prescription RT doses or RT in combination with systemic therapy. [ABSTRACT FROM AUTHOR]

Abstract Aim We present the final results of the BONADIUV trial, a single-blind, randomised, placebo-controlled phase 2 study to evaluate the impact of ibandronate treatment on bone mineral density (BMD) in osteopenic women taking aromatase inhibitors (AI). Patients and methods Between 2011 and 2014, 171 osteopenic patients were randomised in a 1:1 ratio to receive either placebo or oral monthly ibandronate (150 mg). Treatment duration was 2 years, with 6-month evaluation. Primary end-point was the 2-year lumbar spine (LS) and total hip (TH) T-score mean differences as measure of BMD variation. Secondary analyses of survival outcomes have been performed at a 5-year median follow-up. ClinicalTrials.gov identifier NCT02616744. Results Median age of study population was 60.2 years (range 44–75). At the database cut-off time, the median follow-up was 63.3 months (range 2.7–87.3). No difference in terms of T-score was shown at baseline between arms both for TH (P = 0.61) and LS (P = 0.96). At 2-year follow up, the mean change was statistically significant in favour of ibandronate arm both at TH (P = 0.0002) and LS (P < 0.0001). No significant difference in terms of adverse events was observed between arms. At a median follow-up of 63.3 months (range 2.7–87.3), the overall survival (OS) rate was 97.5% in the placebo group and 93.0% in the ibandronate arm (P = 0.19). The invasive disease-free survival (iDFS) rates did not differ between groups (P = 0.42). Conclusions Ibandronate compared to placebo improved BMD change in osteopenic women treated with adjuvant AI. Five-year survival analyses showed no difference between arms in terms of OS and iDFS rates. Highlights • Bisphosphonates prevent bone loss in adjuvant osteopenic breast cancer patients. • A bone loss prevention strategy for patients receiving adjuvant AI is crucial. • Longer follow-up and further investigations are warranted. [ABSTRACT FROM AUTHOR]

BRCA1/2 mutations are involved in breast cancer (BC) susceptibility but their influence on outcome is unclear. We reviewed BC patients tested for BRCA to determine biological features and influence on outcome. BRCA‐1 was correlated to younger age (P = 0.035), nodal involvement (P = 0.030), higher tumor grade (P = 0.0022) and Ki‐67 (P = 0.014), ER/PgR negative status (P = 0.00042 and 0.0091, respectively), and use of adjuvant chemotherapy (P = 0.000038); BRCA was neither predictive for chemotherapy administration nor resulted in impaired outcome or occurrence of secondary BC. BRCA status did not influence outcome despite higher biological aggressiveness and younger age at presentation. [ABSTRACT FROM AUTHOR]

Purpose. The prevalence of invasive lobular carcinoma (ILC), the second most common type of breast cancer, accounts for 5%–15% of all invasive breast cancer cases. Its histological feature to spread in rows of single cell layers explains why it often fails to form a palpable lesion and the lack of sensitivity of mammography and ultrasound (US) to detect it. It also has a higher incidence of multifocal, multicentric, and contralateral disease when compared to the other histological subtypes. The clinicopathologic features and outcomes of Invasive Ductolobular Carcinoma (IDLC) are very similar to the ILC. The purpose of our study is to assess the importance of MRI in the preoperative management and staging of patients affected by ILC or IDLC. Materials and Methods. We identified women diagnosed with ILC or IDLC. We selected the patients who had preoperative breast MRI. For each patient we identified the areas of multifocal, multicentric, or contralateral disease not visible to standard exams and detected by preoperative MRI. We analyzed the potential correlation between additional cancer areas and histological cancer markers. Results. Of the 155 women who met our inclusion criteria, 93 (60%) had additional cancer areas detected by MRI. In 61 women, 39,4% of the overall population, the additional cancer areas were confirmed by US/tomosynthesis second look and biopsy. Presurgical MRI staging changed surgical management in the 37,4% of the patients. Only six patients of the overall population needed a reoperation after the initial surgery. No statistically significant correlation was found between MRI overestimation and the presence of histological peritumoral vascular/linfatic invasion. No statistically significant correlation was found between additional cancer areas and histological cancer markers. Conclusions. Our study suggests that MRI is an important tool in the preoperative management and staging of patients affected by lobular or ductolobular invasive carcinoma. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objectives: The aim of our work was to report on the clinical outcome of a moderately hyprofractionated radiotherapy regimen in elderly patients affected by head and neck squamous cell carcinoma (HNSCC).Material and Methods: HNSCC aged ≥65 deemed unsuitable for curatively-intended concurrent chemo-radiotherapy or high-dose radiotherapy by clinical judgement were further evaluated with the Geriatric 8 (G8) questionnaire and Charlson comorbidity index (CCI). In case of a G8 score ≤14, a de-intensified radiation schedule of 40 Gy delivered in 16 fractions was prescribed.Results: Thirty-six patients were treated between 2011 and 2016. The median age of the cohort was 77.5 (range: 65-91 years) with a combined ECOG PS of 2-3 in 77.8% and CCI of ≥8 in 25% patients, respectively. At a median follow-up of 13 months (range 2-62 months), the 6-month and 1-year rates of loco-regional control and progression-free survival were 42%, 28% and 36% and 20%, respectively. At univariate analysis, log-rank test showed that age >75 years (p=0.036), worse PS (ECOG≥2; p=0.027), lower G8 score (<9; p=0.027) and PTV volume greater than 200 cc (p=0.038) had a significant correlation with PFS. The negative impact of the PTV volume on PFS was the only parameter confirmed in the multivariate analysis (HR 2.68; 95% CI: 1.24-5.81, p=0.013). No grade 4-5 toxicity was observed, while 13/36 patients (36%) had G3 acute side effects.Conclusion: The hypofractionated radiation schedule evaluated provides clinical benefit with low toxicity in frail, elderly patients affected by locally advanced HNSCC. [ABSTRACT FROM AUTHOR]

Robotic Stereotactic Body Radiotherapy (SBRT) employs radiopaque fiducial markers implanted near the tumor for real-time tracking. Fiducials are usually placed before simulation under CT or ultrasound guidance. This represents a limitation to treatment availability and may result in potential treatment delay. In our Institution, an in-house percutaneous CTguided fiducial placement procedure was implemented for pelvic SBRT. The aim of our study is to evaluate the performance and side effects of in-house fiducial placement. Methods: Patients underwent percutaneous fiducial insertion with a 18 G needle under CT guidance, using a radiopaque skin marker to calculate the depth of target location from body surface (Figure 1). One week after placement, simulation CT and orthogonal X-ray imaging were acquired to verify fiducial usability for SBRT tracking. Data from a consecutive cohort of patients treated with fiducial-guided, robotic-arm pelvic SBRT were collected from January 2018 to September 2021. Success rate was defined as the implanted/tracked fiducials ratio. Kruskal Wallis-test was used to compare median success rate over time. Results: In the observed time frame, 282 patients underwent CT-guided fiducial placement, accounting for 883 implanted fiducials (median 3, range 1-4). Implantation sites were the prostate bed, extra-spinal bones and pelvic lymph nodes in 158 (56%), 37 (13%) and 87 (31%) patients, respectively. Side effects consisted of minor bleeding at the insertion site and transient pain requiring medication after 24 hours in 5 patients (2%). No grade >2 toxicity was observed. Overall success rate was 86% (719/833); median success rate per procedure was 100% (range 50-100%). Among the 114 fiducials rejected for tracking, failure was due to migration in 63 cases (55%) and misplacement in 51 cases (45%). Overall success rate increased across the observed time window from 2018 (53/73, 74%) to 2019 (245/293, 84%) to 2020 (246/272, 90%) to 2021 (175/195, 90%) (Figure 2). A consistent, statistically significant improvement in median success rate was observed over time from 2018 (75%, Interquartile Range, IQR 67-100%) to 2019 (100%, IQR 75-100%) to 2020 (100%, IQR 75-100%) to 2021 (100%, IQR 100- 100%) : p= 0.0008. Conclusions: Our in-house percutaneous CT-guided fiducial placement is a safe procedure requiring minimal standard equipment, resulting in success rates comparable with published experiences performed in a dedicated interventional radiology setting. A consistent improvement in median success rate was observed over 4 years, suggesting the need for appropriate interventions to shorten the learning curve. [ABSTRACT FROM AUTHOR]

Purpose: To assess the outcomes of a cohort of bone oligometastatic prostate cancer patients treated with PSMA-PET guided stereotactic body radiotherapy (SBRT) Methods: From April 2017 to January 2021, 40 patients with oligorecurrent prostate cancer detected by PSMAPET were treated with SBRT for bone oligometastases. Concurrent androgen deprivation therapy was an exclusion criterion. A total of 56 prostate cancer bone oligometastases were included in the present analysis. In 28 patients (70%), oligometastatic disease presented as a single lesion, two lesions in 22.5%, three lesions in 5%, four lesions in 2.5%. Results: 30.3% were spine-metastases, while 69.7% were non-spine metastases. SBRT was delivered for a median dose of 30 Gy (24-40Gy) in 3-5 fractions, with a median EQD2=85 Gy2 (64.3 - 138.9Gy2). With a median followup of 22 months (range, 2-48 months), local control (LC) 1- and 2-years rates were 96.3% and 93.9%, while distant progression-free survival (DPFS) rates were 45.3% and 27%. At multivariate analysis, the lower PSA nadir value after SBRT remained significantly related to better DPFS rates (p=0.03). In 7 patients, a second SBRT course was proposed with concurrent ADT, while 11 patients, due to polymetastatic spread, received ADT alone, resulting in 1- and 2-years ADT-free survival rates of 67.5% and 61.8%. At multivariate analysis, a lower number of treated oligometastases maintained a correlation with higher ADT-free survival rates (p=0.04). Conclusions: In our experience, PSMA-PET guided SBRT resulted in excellent results in terms of clinical outcomes, representing a helpful tool with the aim to delay the start of ADT. [ABSTRACT FROM AUTHOR]

Purpose or objective: Stereotactic Body Radiotherapy (SBRT) is widely used for treatment of uncomplicated spine metastases to palliate symptoms and prolong disease control. However, criteria for patient selection are not available. The aim of this study is to identify determinants of local failure and progression-free interval in patients treated with SBRT to spinal metastases. Materials and methods: Data from consecutive patients treated with Cyberknife-based spine SBRT between January 2019 and March 2020 were retrospectively collected. Dose was expressed as Biological Effective Dose for α/β=10 (BED10). Kaplan-Meyer method was used to calculate Local Control (LC) and Disease Free Survival (DFS) from date of SBRT to event. Univariate (UVA) and Multivariate analysis (MVA) were performed using log-rank and Cox model, respectively. Results: Sixty-two patients accounting for 70 spinal metastases were included. Median age was 66 (range 32- 87) years. Disease was metastatic at diagnosis in 21 patients (34%) : an active primary tumor was present in 17 patients (27%). Among treated sites, most represented primary malignancies were prostate (n=28, 40%) and breast (n=21, 30%). Dose regimens consisted of 25-30 Gy in 5 fractions and 21-30 Gy in 3 fractions in respectively 61 (87%) and 9 (13%) cases, resulting in a median BED of 43.2 (range 37.5-60) Gy10. Concurrent chemotherapy (including cytotoxic or targeted agents) was administered in 43% of cases (n=30). After a median follow up of 10 months (range 1-24 months), 9 local relapses and 40 distant progressions were observed. One year LC was 87% (Fig.1): nonprostate primary tumor (p=0.003, Fig.2) and concurrent chemotherapy (p=0.006, Fig.3) were associated to poorer LC at UVA, and an independent correlation was confirmed at MVA (respectively p=0.017 and p=0.024). One-year DFS was 43% (Fig.4). UVA showed a correlation between impaired DFS and active primary tumor (p=0.003), metastatic dissemination at diagnosis (p=0.02) and nonprostate primary tumor (p=0.009), although only an active primary tumor site was independently associated to DFS at MVA (p=0.007, Fig.5). Only G2 acute pain or nausea were observed. No late toxicity, in particular vertebral fracture, was reported. Conclusion: Spine SBRT results in high LC rates and durable progression-free survival with low incidence of mild toxicity. Clinical nomograms based on patient-related characteristics may help to select candidates for this approach. [ABSTRACT FROM AUTHOR]

Background: The aim of the present study is to evaluate the impact of metastases-directed stereotactic body radiotherapy in two groups of oligometastatic prostate cancer (PC) patients: oligorecurrent PC and oligoprogressive castration-resistant PC (oligo-CRPC).Methods: Inclusion criteria of the present multicentre retrospective analysis were: (1) oligorecurrent PC, defined as the presence of 1-3 lesions (bone or nodes) detected with choline positron emission tomography or CT plus bone scan following biochemical recurrence; (2) oligo-CRPC, defined as metastases (bone or nodes) detected after a prostatic-specific antigen rise during androgen deprivation therapy (ADT). Primary end points were: distant progression-free survival (DPFS) and ADT-free survival in oligorecurrent PC patients; DPFS and second-line systemic treatment-free survival in oligo-CRPC patients.Results: About 100 patients with oligorecurrent PC (139 lesions) and 41 with oligo-CRPC (70 lesions), treated between March 2010 and April 2016, were analysed. After a median follow-up of 20.4 months, in the oligorecurrent group 1- and 2-year DPFS were 64.4 and 43%. The rate of LC was 92.8% at 2 years. At a median follow-up of 23.4 months, in the oligo-CRPC group 1- and 2-year DPFS were 43.2 and 21.6%. Limitations include the retrospective design.Conclusions: Stereotactic body radiotherapy seems to be a useful treatment both for oligorecurrent and oligo-CRPC. [ABSTRACT FROM AUTHOR]

Background Accelerated partial breast irradiation (APBI) represents a valid option for selected early breast cancer (BC). We recently published the 5-year results of the APBI-IMRT-Florence phase 3 randomised trial ( NCT02104895 ), showing a very low rate of disease failure, with acute and early–late toxicity in favour of APBI. We present the early and 2-year follow-up health-related quality of life (HRQoL) results. Methods Eligible patients were women aged more than 40 years with early BC suitable for breast-conserving surgery. APBI consisted of 30 Gy in five fractions delivered with IMRT technique. Standard whole breast irradiation (WBI) consisted of 50 Gy in 25 fractions plus a 10 Gy in five fractions boost on tumour bed. A total of 520 patients were enrolled in the phase 3 trial. Overall, 205 patients (105 APBI and 100 WBI) fully completed all the given questionnaires and were therefore included in the present analysis. As HRQoL assessment, patients were asked to complete the European Organisation for Research and Treatment of Cancer QLQ-C30, and the BR23 questionnaires at the beginning (T0), at the end (T1) and after 2 years from radiation (T2). Findings No significant difference between the two arms at QLQ-C30 and BR23 scores emerged at T0. Global health status (p = 0.0001), and most scores of the functional and symptom scales of QLQ-C30 at T1 showed significant differences in favour of the APBI arm. Concerning the BR23 functional and symptom scales, the body image perception, future perspective and breast and arm symptoms were significantly better in the APBI group. Similar significant results emerged at T2: significant differences in favour of APBI emerged for GHS (p = 0.0001), and most functional and symptom QLQ-C30 scales. According to QLQ-BR23 module, among the functional scales, the body image perception and the future perspective were significantly better in the APBI group (p = 0.0001), whereas among the symptom scales significant difference emerged by breast and arm symptoms with better outcomes in APBI arm (p < 0.01). Interpretation Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. APBI should be strongly considered in the treatment choice for selected low-risk patients. Mature local control results from ongoing adequately powered randomised trials are awaited. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemotherapy (NAC) is widely used in locally advanced breast cancer (BC) treatment. The role of postmastectomy radiotherapy (PMRT) after NAC is strongly debated. The aim of our analysis was to identify major prognostic factors in a singlecenter series, with emphasis on PMRT. From 1997 to 2011, 170 patients were treated withNACand mastectomy at our center; 98 cases (57.6%) underwent PMRT and 72 cases (42.4%) did not receive radiation. At amedian follow-up period of 7.7 years (range 2-16) for the whole cohort, median time to locoregional recurrence (LRR) was 3.3 years (range 0.7-12.4). The 5-year and 10-year actuarial LRR rate were 14.5% and 15.9%, respectively. At the multivariate analysis the factors that significantly correlated with survival outcome were =4 positive nodes (HR 5.0, 1.51-16.52; P = 0.035), extracapsular extension (HR 2.18, 1.37-3.46; P = 0.009), and estrogen receptor positive disease (HR 0.57, 0.36-0.90; P = 0.003). Concerning LRR according to use of radiation, PMRT reduced LRR for patient with clinical T3 staged disease (P = 0.015). Our experience confirmed the impact of pathological nodal involvement on survival outcome. PMRT was found to improve local control in patients presenting with clinical T3 tumors, regardless of the response to chemotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: This is a safety and efficacy analysis from a very large dataset of patients affected by localized prostate cancer having received radiotherapy with or without concomitant androgen deprivation therapy in twelve academic and non-academic Italian Institutions. The aim of this retrospective "real life" study was to provide additional data on clinical presentation, diagnostic workup, radiation therapy management and toxicity as collected within the framework of POP III. Though the usual limitations for a retrospective analysis apply, it nevertheless may expand the current knowledge in this area showing the progress of radiation therapy techniques and clinical outcomes in the period between 2004 and 2011 after a significant period of follow up. Background and purpose: Two previous "Patterns Of Practice" surveys (POP I and POP II), including more than 4000 patients affected by prostate cancer treated with radical external beam radiotherapy (EBRT) between 1980 and 2003, established a "benchmark" Italian data source for prostate cancer radiotherapy. This report (POP III) updates the previous studies. Methods: Data on clinical management and outcome of 2525 prostate cancer patients treated by EBRT from 2004 to 2011 were collected and compared with POP II and, when feasible, also with POP I. This report provides data on clinical presentation, diagnostic workup, radiation therapy management, and toxicity as collected within the framework of POP III. Results: More than 50% of POP III patients were classified as low or intermediate risk using D'Amico risk categories as in POP II; 46% were classified as ISUP grade group 1. CT scan, bone scan, and endorectal ultrasound were less frequently prescribed. Dose-escalated radiotherapy (RT), intensity modulated radiotherapy (IMRT), image guided radiotherapy (IGRT), and hypofractionated RT were more frequently offered during the study period. Treatment was commonly well tolerated. Acute toxicity improved compared to the previous series; late toxicity was influenced by prescribed dose and treatment technique. Five-year overall survival, biochemical relapse free survival (BRFS), and disease specific survival were similar to those of the previous series (POP II). BRFS was better in intermediate- and high-risk patients treated with ≥ 76 Gy. Conclusions: This report highlights the improvements in radiotherapy planning and dose delivery among Italian Centers in the 2004–2011 period. Dose-escalated treatments resulted in better biochemical control with a reduction in acute toxicity and higher but acceptable late toxicity, as not yet comprehensively associated with IMRT/IGRT. CTV-PTV margins >8 mm were associated with increased toxicity, again suggesting that IGRT—allowing for tighter margins—would reduce toxicity for dose escalated RT. These conclusions confirm the data obtained from randomized controlled studies. [ABSTRACT FROM AUTHOR]

• Stereotactic radiosurgery (SRS) is an option in patients with brain metastases (BM). • No consensus on optimal salvage modality for local failure in BM after SRS. • Stereotactic reirradiation (SRS2) is an option despite concern for Radionecrosis (RN). • A systematic review was carried out to test efficacy and safety of SRS2. • Eleven studies were included. • Pooled 1-year Local Failure rate was 24 % and median Overall Survival was 14 months. • A pooled crude RN rate of 13 % was reported. • SRS2 is an effective option in patients with recurrent BM following prior SRS. 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). 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. 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). SRS2 is an effective strategy for in-site recurrence of BM previously treated with SRS. [ABSTRACT FROM AUTHOR]