Whole Breast Irradiation Versus Intraoperative Electron Radiation Therapy for Breast Conserving Therapy: A Large Mature Single Institution Matched-Pair Evaluation of True Local Relapse, Progression Free Survival, and Overall Survival.

PURPOSE: Comparative outcome data after intraoperative radiation therapy and whole breast irradiation (WBI) for breast cancer at >10 years median follow-up are rare. We present a mature, single-institution, matched-pair comparison reporting survival and relapse rates in patients treated with either modality. METHODS AND MATERIALS: Complete data sets for 258 intraoperative electron radiation therapy (IOERT) patients treated between 2000 and 2010 were matched with 258 patients postoperatively treated with WBI by age/histology/tumor size, grading/lymph-node-status/hormone receptors/type of adjuvant therapy/surgical margins, and treatment date. Relapse at surgical intervention site was classified as true local recurrence (LR). All recurrences in the treated breast (any quadrant) were classified as ipsilateral recurrence (IR). RESULTS: Median follow-up was 157 months (12-251) for the IOERT group and 154 months (31-246) for the WBI group. Cumulative incidence of IR at 5, 10, and 15 years was 2.4%, 7.9%, and 12.7% for IOERT and 1.2%, 4.1%, and 5.0% for WBI (P = .02). Cumulative incidence of LR at 5, 10, and 15 years was 1.6%, 5.1%, and 8.3% for IOERT and 0.4%, 2.1%, and 2.5% for WBI (P = .02). No differences in overall survival, disease-free survival, second cancer incidence, or cardiac events were recorded in either treatment group. Outcome was better in the accelerated partial breast irradiation (APBI)-suitable group than in the APBI-unsuitable group (2009 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 0% vs 7.3%, 6.1% vs 13.3%, and 7.3% vs 19.9% for IOERT and 0% vs 1.8%, 2.0% vs 3.9%, and 3.1% vs 3.9% for WBI) and in the revised APBI-suitable group than in the APBI-cautionary group (2017 criteria) (cumulative incidence of IR at 5, 10, and 15 years was 1.1% vs 6.4%, 6.2% vs 13.3%, and 7.8% vs 27.5% for IOERT and 1.7% vs 0%, 4.1% vs 4.4%, and 5.4% vs 4.4% for WBI). CONCLUSIONS: The IR and LR rate were higher after IOERT than after WBI for the American Society for Radiation Oncology suitable patient group, although without reaching statistical significance. Thus, IOERT could be an alternative to WBI upon stringent patient selection, but patients should be counseled carefully about the potential for increased IR rate with IOERT. Second cancer incidence and cardiac events did not differ between IOERT and WBI.

Stereotactic Body Radiation Therapy for Intermediate-risk Prostate Cancer With VMAT and Real-time Electromagnetic Tracking: A Phase II Study.

OBJECTIVES: Stereotactic body radiation treatment represents an intriguing therapeutic option for patients with early-stage prostate cancer. In this phase II study, stereotactic body radiation treatment was delivered by volumetric modulated arc therapy with flattening filter free beams and was gated using real-time electromagnetic transponder system to maximize precision of radiotherapy and, potentially, to reduce toxicities. MATERIALS AND METHODS: Patients affected by histologically proven prostate adenocarcinoma and National Comprehensive Cancer Network (NCCN) intermediate class of risk were enrolled in this phase II study. Beacon transponders were positioned transrectally within the prostate parenchyma 7 to 10 days before simulation computed tomography scan. The radiotherapy schedule was 38 Gy in 4 fractions delivered every other day. Toxicity assessment was performed according to Common Terminology Criteria for Adverse Events (CTCAE), v4.0. RESULTS: Thirty-six patients were enrolled in this study. Median initial prostate-specific antigen was 7.0 ng/mL (range: 2.3 to 14.0 ng/mL). Median nadir-prostate-specific antigen after treatment was 0.2 ng/mL (range: 0.006 to 4.8 ng/mL). A genitourinary acute toxicity was observed in 21 patients (dysuria grade [G] 1: 41.7%, G2: 16.7%). Gastrointestinal acute toxicity was found in 9 patients (proctitis G1: 19.4%, G2: 5.6%). Late toxicity was mild (genitourinary toxicity G1: 30.6%; G2: 8.3%; gastrointestinal toxicity G1: 13.9%; G2: 19.4%). At a median follow-up time of 41 months, 3 biochemical recurrences were observed (2 local recurrences, 1 distant metastasis). Three-year biochemical recurrence-free survival was 89.8% (International Society of Urologic Pathology Grade Group 2: 100%, Grade Group 3: 77.1%, P=0.042). CONCLUSION: Ultrahypofractionated radiotherapy, delivered with flattening filter free-volumetric modulated arc therapy and gated by electromagnetic transponders, is a valid option for intermediate-risk prostate cancer.

Hypofractionated Whole Breast Irradiation and Simultaneous Integrated Boost in Large-breasted Patients: Long-term Toxicity and Cosmesis.

INTRODUCTION: The purpose of this study was to evaluate the impact of breast size on long-term toxicity and cosmesis in patients with breast cancer treated with hypofractionated simultaneous integrated boost (SIB) using volumetric modulated arc therapy (VMAT). PATIENTS AND METHODS: Patients with early stage breast cancer were treated with 3-week hypofractionated SIB-VMAT to the whole breast (40.5 Gy) and tumor bed (48 Gy). Two cohorts were identified: small/medium- (< 1000 cm3) and large- (> 1000 cm3) breasted patients. Acute and late (at 2 and 5 years) skin toxicity and cosmetic data were analyzed. Univariate and multivariate analysis evaluated associations between toxicity and dosimetric/anatomical variables. RESULTS: From August 2010 to March 2017, a total of 1160 patients were treated; 831 had at least 2 years of follow-up and were analyzed. Treated skin area (TSA) receiving at least 20 Gy > 400 cm2 and V105% of Boost > 5 cm3 were significant predictors for acute skin toxicity. Multivariate analysis at 2 years was significant for boost volume > 70 cm3, TSA > 400 cm2, and breast size > 1500 cm3. At 5 year analysis (352 patients), none of the analyzed variables was significant. For cosmetic outcome, only the breast size (> 1000 cm3) and the boost size > 70 cm3 at 2 and 5 years, respectively, confirmed significance. CONCLUSIONS: The TSA > 400 cm2 resulted as a significant predictor of both acute and late skin toxicity at 2 years; however, at 5 years, no breast size or dosimetric parameter suggested indications for increased toxicity. A worse cosmetic outcome was recorded at the 2-year follow up for large breasts, but was not confirmed at the 5-year follow-up. These long-term data suggest that hypofractionated SIB-VMAT is a viable modality also in large-breasted patients.

Multimodality imaging of adult rhabdomyosarcoma: the added value of hybrid imaging.

Rhabdomyosarcoma (RMS) represents more than 50% of paediatric soft tissue tumours. Conversely, it is extremely rare among adults, where it shows peculiar biological and clinical features that are still poorly investigated. RMS patients should be referred to a Sarcoma Centre, where the contribution of experienced radiologists plays a relevant role in the diagnostic assessment of the disease, including precise localisation, staging, image-guided biopsy, response evaluation after treatment and follow-up. Besides CT and MRI, hybrid imaging including positron emission tomography (PET)/CT and PET/MRI are giving an increasing contribution to provide functional insights about tumour biology and to improve the diagnostic accuracy of the imaging work-up. This review paper provides a revision of the pathology, clinical and radiological features of adult RMS, with a particular focus on the growing role of hybrid PET-based imaging.

Linac-based stereotactic body radiation therapy for low and intermediate-risk prostate cancer : Long-term results and factors predictive for outcome and toxicity.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is considered an effective and safe treatment in patients with low- and intermediate-risk prostate cancer (PC). However, due to a lack of long-term follow-up and late toxicity data, this treatment is not universally accepted. The present study aimed to evaluate outcome and early and late toxicity in a cohort of patients with low- and intermediate-risk PC treated prospectively with linear accelerator (linac)-based SBRT. PATIENTS AND METHODS: Patients with low- or intermediate-risk (NCCN criteria) PC were included. All patients received linac-based SBRT to 35 Gy in 5 fractions delivered on alternate days. Endpoints were toxicity, biochemical relapse-free survival (BRFS), metastatic progression-free survival (mPFS), and overall survival (OS). RESULTS: From 2012 to 2018, 178 patients were treated. Median baseline prostate-specific antigen (iPSA) was 6.37 ng/ml (range 1.78-20). Previous transurethral resection of the prostate (TURP) was present in 23 (12.9%) patients. Median follow-up was 58.9 months (range 9.7-89.9). BRFS rates at 1, 3, and 5 years were 98.3 (95% confidence interval, CI, 94.7-99.4%), 94.4 (95%CI 89.4-97), and 91.6% (95%CI 85.4-95.2), respectively. In univariate analysis, performance status (PS), iPSA, and nadir PSA (nPSA) were correlated with BRFS. In multivariable analysis iPSA and nPSA remained significant. BRFS rates at 5 years were 94.9% (95%CI 86.8-98) for International Society of Urological Pathology (ISUP) grade group 1, 93.2% (95%CI 80.5-97.7) for ISUP group 2, and 74.8% (95%CI 47.1-89.5) for ISUP group 3. At 1, 3, and 5 years, mPFS rates were 98.8 (95%CI 95.5-99.7), 96.2 (95%CI 91.9-98.3), and 92.9% (95%CI 87.2-96.2), respectively; OS rates were 100, 97.2 (95%CI 92.9-98.9), and 95.1% (95%CI 90-97.6), respectively. One (0.56%) case of grade 3 acute genitourinary (GU), one case of acute gastrointestinal (GI), and one case of grade 3 late GU toxicity were observed. GI toxicity positively correlated with prostate volume. CONCLUSION: At long-term follow-up, linac-based SBRT continues to be a valid option for the management localized PC. Biochemical control remains high at 5 years, albeit with some concerns regarding the optimal schedule for unfavorable intermediate-risk PC. Considering the excellent prognosis, patient selection is crucial for prevention of severe late toxicity.

Recursive partitioning model-based analysis for survival of colorectal cancer patients with lung and liver oligometastases treated with stereotactic body radiation therapy.

INTRODUCTION: Liver and lung are common sites of metastases from colorectal cancer (CRC). Stereotactic body radiation therapy (SBRT) represents a valid treatment, with high rates of local control (LC). In this study, we applied recursive partitioning model-based analysis (RPA) to define class risks for overall survival (OS) and progression free survival (PFS) in oligometastatic CRC patients. MATERIALS AND METHODS: In this monocentric analysis, we included patients with lung or liver metastases. Patients were candidate to SBRT if a maximum of 5 metastases. End points of the present analysis were LC, PFS, and OS. The binary classification tree approach with RPA was applied to stratify the patients into risk groups based on OS and PFS. RESULTS: 218 patients were treated with SBRT on 371 metastases. Majority of patients (56%) was treated on single lesion, followed by 2 (26.1%) and 3 lesions (14.7%). Median follow-up was 22.7 months. Rates of LC were 84.2% at 1 year and 73.8% at 3 years. Rates of PFS at 1 and 3 years were 42.2% and 14.9%, respectively. RPA identified 3 classes for PFS, according to age and number of metastases with 3-year PFS of 30.6%, 13.5% and 8.4%. Overall survival was 87.2% at 1 year, 51.9% at 3 years, and 36.8% at 5 years. RPA identified 3 nodes. Class 1 included patients with liver metastases (3-year OS 35.2%). Class 2 included patients with lung metastases and DFI ≤ 48 months (3-year OS 65%). Class 3 included patients with lung metastases and DFI > 48 months (3-year OS 73.5%). CONCLUSIONS: Stereotactic body radiation therapy can be considered an effective treatment for the management of liver and lung metastases from CRC. With RPA, we identified prognostic risk class to define patients who could benefit the most from SBRT.

Role of stereotactic body radiation therapy in the treatment of liver metastases: clinical results and prognostic factors.

PURPOSE: To evaluate feasibility and efficacy of Stereotactic Body Radiation Therapy (SBRT) for unresectable liver metastasis in oligometastatic patients. METHODS: Oligometastatic patients with up to three liver metastases of a maximum diameter of 6 cm were treated with SBRT. Total dose was 75 Gy in three consecutive fractions. Study endpoints were efficacy of this fractionation in terms of local control (LC), overall survival (OS), toxicity, and prognostic factors affecting OS and LC. RESULTS: Between February 2010 and December 2016, we enrolled 202 patients, with a total of 268 unresectable liver metastases. Median follow-up time from SBRT was 33 months (5-87 months). One-, 3­, and 5­year LC rates were 92%, 84%, and 84%, respectively. In univariate analysis, the primary histology and previous local ablative therapies were significant. Median OS was 21 months and the survival rates were 79%, 27%, and 15% at 1, 3, and 5 years after SBRT, respectively. At univariate analysis, sex, primary disease histology, intra-, and extra-hepatic progression were significant prognostic factors. This analysis confirmed the absence of late toxicity >G3. CONCLUSION: This study confirms the efficacy and safety of SBRT for unresectable liver metastases. Selection of cases may improve survival and LC.

Volumetric Modulated Arc Therapy After Lung Sparing Surgery for Malignant Pleural Mesothelioma: A Single Institution Experience.

INTRODUCTION: We investigated the possible role of volumetric modulated arc therapy (VMAT) in the setting of adjuvant treatment of malignant pleural mesothelioma (MPM) after lung-sparing surgery with pleurectomy and decortication. MATERIALS AND METHODS: Patients affected by MPM who had undergone pleurectomy and decortication and adjuvant radiotherapy with VMAT were included. The endpoints of the present analysis were local control, progression-free survival, and overall survival. Assessment of the variables affecting survival was performed using univariate and multivariate Cox proportional hazard models. RESULTS: A total of 49 patients were included in the present study. Of the 49 patients, 96% had been treated with a trimodality approach. Radiotherapy was delivered to a median dose of 44 Gy in 22 fractions (range, 22-59.4 Gy). The treatment was well tolerated, with just 2 grade 3 acute toxicities, 1 grade 5, and 2 grade 4 toxicities recorded during the follow-up period. The median follow-up period was 27.4 months. The local control rate at 12, 24, and 36 months was 75.2%, 67.4%, and 56.5%, respectively. The median progression-free survival was 14.9 months (95% confidence interval [CI], 7.5-25.2). The median overall survival was 21.5 months (95% CI, 15.3-37.1). On multivariate analysis, the administration of carboplatin- instead of cisplatin-based chemotherapy (hazard ratio, 2.97; 95% CI, 1.22-7.26; P = .017) and R2 resection (hazard ratio, 1.95; 95% CI, 1.27-2.99; P = .002) showed a negative correlation with overall survival. On univariate analysis, the percentage of the heart receiving >20 Gy and >30 was associated with the occurrence of late pneumonitis (P = .018 and P = .077). CONCLUSION: VMAT is feasible in the setting of MPM after lung-sparing surgery. The toxicity rates were reduced with this technique compared with historical data of older techniques. Local and distant failure remain a major issue to be addressed in future trials.

Predictive factors for survival outcomes of oligometastatic prostate cancer patients treated with metastases-directed therapy: a recursive partitioning-based analysis.

PURPOSE: The aim of the present study was to provide predictive factors for survival outcomes of oligometastatic prostate cancer (PC) patients treated with stereotactic body radiation therapy (SBRT) as a metastases-directed therapy (MDT). METHODS: In this cohort study, endpoints included overall survival (OS), progression-free survival (PFS), distant progression-free survival (DFS) and local control of treated metastases (LC). The binary classification tree approach with recursive partitioning analysis (RPA) was applied to stratify the patients into risk groups based on OS, PFS and DPFS; for each endpoint, disease-free interval (DFI) was calculated. We included patients with synchronous or metachronous metastases from prostate adenocarcinoma treated with SBRT. RESULTS: 119 Metastases were treated with SBRT in 92 patients. Median follow-up was 22.2 months. Rates of OS at 1 and 3 years were 96.9% and 88.0%, while DPFS was 51.9% and 20.9%. Recursive partitioning analysis identified three prognostic classes for OS: Class 1: castration-sensitive patients (3 years OS 95%); Class 2: castration-resistant patients with low-intermediate risk NCCN disease (3 years OS 88.8%); Class 3: castration-resistant patients with high-risk NCCN disease (3 years OS 76.9%). Regarding DPFS, RPA divided patients into two classes, according to a cutoff value of DFI of 34 months (3 years PFS of 28.7% vs 5.8%). Three classes were identified for DPFS: Class 1: DFI < 34 months (3 years DPFS 9.1%); Class 2: DFI > 34 months and high-risk NCCN PC (3 years DPFS 21%); Class 3: DFI > 34 months and low-intermediate risk NCCN disease (3 years DPFS 60.2%). CONCLUSION: Oligometastatic PC represents nowadays a setting of particular interest in which local ablative therapies play a decisive role. In the present study, we recognized the importance of DFI, together with NCCN class risk, to predict the risk of new metastases after SBRT in oligometastatic PC.

Adjuvant volumetric modulated arc therapy compared to 3D conformal radiation therapy for newly diagnosed soft tissue sarcoma of the extremities: outcome and toxicity evaluation.

OBJECTIVE: To assess the impact of adjuvant volumetric modulated arc therapy (VMAT) compared with three-dimensional conformal radiation therapy (3DCRT) in terms of toxicity and local control (LC) in patients with soft tissue sarcoma of the extremities. METHODS: From 2004 to 2016, 109 patients were treated, initially using 3DCRT and subsequently with VMAT. Clinical outcome was evaluated by contrast-enhanced MRI, thoracic and abdominal CT 3 months after treatments and then every 6 months. Toxicity was evaluated with Common Terminology Criteria for Adverse Events scale v. 4.3. RESULTS: Patients presented Stage III soft tissue sarcoma disease (77%), localized tumor (95%) at the lower extremity (87%), adipocytic histotype (46%). Surgical resection was performed in all patients, followed by adjuvant 3DCRT in 38, and VMAT in 71. The median total dose was 66 Gy/33 fractions (range 60-70 Gy;25-35 fractions). More successful bone sparing was recorded using VMAT (p < 0.001). Median follow-up was 61 months, 93 and 58 months for 3DCRT and VMAT group, respectively. The 2- and 5 year LC were 95.3±2.1%, and 87.4±3.4% for the whole cohort, 92.0±4.5%, 82.9±6.4% for 3DCRT, 97.1±2.0%, 89.6±4.1% for VMAT (p = 0.150). On univariate and multivariate analysis the factors recorded as conditioning LC were the status of the surgical resection margins (p = 0.028) and the total dose delivered (p = 0.013). CONCLUSION: The availability of modern radiotherapy technique permit a better conformity on the target with maximum sparing of normal tissue and acceptable side-effects. VMAT is a safe and feasible treatment with limited rate of toxicity, compared to 3DCRT. Results on LC of VMAT are encouraging. ADVANCES IN KNOWLEDGE: Soft tissue sarcoma of the extremities can benefit from the use of VMAT, with a reduction of the high dose to bones to avoid radiation osteonecrosis. An adequate total dose of at least 66 Gy and a radical surgical margin allow a good local control.

Reirradiation of Locally Recurrent Prostate Cancer With Volumetric Modulated Arc Therapy.

PURPOSE: This study explores the efficacy and safety of reirradiation with modern radiation therapy techniques in patients previously irradiated for prostate cancer and affected by local relapse of disease. METHODS AND MATERIALS: Patients affected by previously irradiated prostate cancer were enrolled in this reirradiation study if they had a biochemical relapse and a 11C-choline positron emission tomography scan revealing the presence of a local recurrence of disease. Reirradiation consisted of a stereotactic treatment delivered by image guided radiation therapy-volumetric modulated arc therapy with flattening filter-free technology in 5 daily fractions. RESULTS: Twenty-three patients underwent reirradiation to the prostate, prostatic bed, or prostate and local recurrence. Re-treatment consisted of a median total dose of 25 Gy in 5 fractions. A biochemical response was observed in all cases. Acute toxicity was mainly genitourinary (GU) grade 1 to 2 (n = 13; 56.5%). One patient (4.3%) had grade 3 hematuria. A grade 1 GU late toxicity was registered in 4 patients (17.4%) and grade 3 in 1 patient (4.3%, urethral obstruction). Gastrointestinal toxicity was negligible. Regression analysis showed that only a short elapsed time in months from primary radiation therapy was significantly correlated with acute GU toxicity. After a median follow-up of 33 months (range, 5-58 months), the median biochemical recurrence-free survival was 19 months, and the 2-year biochemical recurrence-free survival (BRFS) was 41.7%. Median local control was 30 months; the 2-year local control rate was 58.1%. CONCLUSIONS: Reirradiation of patients with prostate cancer who underwent previous radiation therapy is a valuable option that can be safely considered to delay the beginning of hormonal treatment.

Linac-based stereotactic body radiation therapy vs moderate hypofractionated radiotherapy in prostate cancer: propensity-score based comparison of outcome and toxicity.

OBJECTIVE: Prostate cancer represents the second most common malignancy in the world and majority of patients have diagnosis of localized disease. The aim of the present study was to compare two cohorts of patients treated with moderate hypofractionation (MHRT) or stereotactic body radiation therapy (SBRT). METHODS: We included patients treated between 2010 and 2015. Inclusion criteria were: adenocarcinoma of the prostate; class risks low or intermediate; WHO performance status 0-2. We evaluated rectal, gastrointestinal toxicity and genitourinary. Measures of outcome were biochemical disease-free survival and overall survival. Propensity score was used to approximate the balance in covariates. RESULTS: 209 patients were included, treated with MHRT (n = 109) or SBRT (n = 100). Median follow-up time was 37.4 months. Rates of biochemical disease-free survival at 1- and 3 years were 100 and 95%, respectively. There was no significant difference between the two groups (p = 0.868). Rates of overall survival at 1- and 3 years were 100 and 97.1%, respectively with no differences between the two groups (p = 0.312). After propensity scoring matching, no differences were observed in terms of acute and late rectal and gastrointestinal toxicity. While mild genitourinary side-effects were more common in SBRT group (45.5% vs 19.5 %), Grade 2 and 3 toxicity was increased after MHRT (11.7% vs 2.6 %; p = 0.029). CONCLUSIONS: Moderate hypofractionation and SBRT are two effective and safe options for the treatment of low- and intermediate-risk prostate cancer. The analysis showed no difference in terms of disease's control and survival but increased moderate and severe toxicity after MHRT. ADVANCES IN KNOWLEDGE: Moderate hypofractionation and SBRT are comparable in terms of efficacy while moderate and severe toxicity is more common in the first one.

Computed tomography based radiomic signature as predictive of survival and local control after stereotactic body radiation therapy in pancreatic carcinoma.

PURPOSE: To appraise the ability of a radiomics signature to predict clinical outcome after stereotactic body radiation therapy (SBRT) for pancreas carcinoma. METHODS: A cohort of 100 patients was included in this retrospective, single institution analysis. Radiomics texture features were extracted from computed tomography (CT) images obtained for the clinical target volume. The cohort of patients was randomly divided into two separate groups for the training (60 patients) and validation (40 patients). Cox regression models were built to predict overall survival and local control. The significant predictors at univariate analysis were included in a multivariate model. The quality of the models was appraised by means of area under the curve and concordance index. RESULTS: A clinical-radiomic signature associated with Overall Survival (OS) was found significant in both training and validation sets (p = 0.01 and 0.05 and concordance index 0.73 and 0.75 respectively). Similarly, a signature was found for Local Control (LC) with p = 0.007 and 0.004 and concordance index 0.69 and 0.75. In the low risk group, the median OS and LC in the validation group were 14.4 and 28.6 months while in the high-risk group were 9.0 and 17.5 months respectively. CONCLUSION: A CT based radiomic signature was identified which correlate with OS and LC after SBRT and allowed to identify low and high-risk groups of patients.

Predictive Factors for Response and Survival in a Cohort of Oligometastatic Patients Treated With Stereotactic Body Radiation Therapy.

PURPOSE: This study evaluated patients, treatment, or disease characteristics that could predict response to stereotactic body radiation therapy (SBRT) and survival in a database of patients with oligometastatic disease from different solid tumors. METHODS AND MATERIALS: Patients treated with SBRT for oligometastatic disease between 2014 and 2015 were included. Patients were defined as oligometastatic if they were affected by a maximum of 5 active lesions in 3 different sites. They had to be treated with SBRT with radical intent. RESULTS: The study included 358 patients. With a median follow-up of 31.83 months, local control at 6 and 24 months was 94.6% and 78.9%, respectively. Distant progression was recorded in 279 patients (77.9%). Progression-free survival at 6 and 24 months was 66.1% and 18.4%, respectively. At last follow-up, 195 patients (54.5%) were still alive in 59 cases with no evidence of disease. The median overall survival (OS) was 34.7 months (95% confidence interval, 29.66-43.83). OS at 6 and 24 months was 96.07% and 63.57%, respectively. On multivariable analysis, the presence of lung metastases (hazard ratio [HR], 0.50 [0.33-0.75]; P = .001) and nodal metastases (HR, 0.44 [0.24-0.78]; P = .005) was related to longer OS. Primary lung cancer (HR, 1.89 [1.14-3.13]; P = .013), increasing age (HR, 1.02 [1.01-1.04]; P = .002), and the presence of metastatic sites other than the irradiated ones (HR, 2.19 [1.39-3.43]; P = .001) were all independent predictors of shorter OS. Local response was associated with OS. CONCLUSIONS: SBRT for patients with oligometastatic disease is effective. Local response is strongly correlated with patients'' prognosis, also underlying its relevance in a metastatic setting.

Role of Stereotactic Body Radiation Therapy for the Management of Oligometastatic Renal Cell Carcinoma.

PURPOSE: Kidney cancer has been increasing 1.7% annually. Renal cell carcinoma is the most common kidney cancer and it can metastasize. Our aim was to analyze patients treated with stereotactic body radiation therapy of renal cell carcinoma metastases. MATERIALS AND METHODS: A total of 58 patients (73 lesions) were treated from 2004 to 2016. Patients were candidates for analysis if a maximum of 3 metastases were diagnosed and the primary tumor was resected. Toxicity was classified according to Common Terminology Criteria for Adverse Events version 3. RESULTS: All patients had renal cell carcinoma, in particular the clear cell type in 82.7%. A total of 39 metastases (53.4%) were located in the lungs and 19 (26%) were in the lymph nodes. Less common were metastases to bone (9.5% of cases), the liver (4.1%) and the adrenal gland (6.8%). Median followup was 16.1 months (range 3.5 to 157.1). The local control rate at 12 and 18 months was 90.2% and 90.2%, respectively. The progression-free survival rate at 12 and 18 months was 46.2% (95% CI 32.2-59) and 35% (95% CI 21.4-48.9), respectively. On univariate and multivariable analyses metachronous and single metastases predicted better progression-free survival. Systemic therapy before stereotactic body radiation therapy predicted improved local control in clear cell cases. CONCLUSIONS: Stereotactic body radiation therapy can be considered a safe approach and it provides effective local control of oligometastatic renal cell carcinoma. However, future prospective studies are necessary to evaluate the impact on survival and quality of life.

Role of Stereotactic Body Radiation Therapy for the Management of Oligometastatic Renal Cell Carcinoma.

PURPOSE: Kidney cancer has been increasing 1.7% annually. Renal cell carcinoma is the most common kidney cancer and it can metastasize. Our aim was to analyze patients treated with stereotactic body radiation therapy of renal cell carcinoma metastases. MATERIALS AND METHODS: A total of 58 patients (73 lesions) were treated from 2004 to 2016. Patients were candidates for analysis if a maximum of 3 metastases were diagnosed and the primary tumor was resected. Toxicity was classified according to Common Terminology Criteria for Adverse Events version 3. RESULTS: All patients had renal cell carcinoma, in particular the clear cell type in 82.7%. A total of 39 metastases (53.4%) were located in the lungs and 19 (26%) were in the lymph nodes. Less common were metastases to bone (9.5% of cases), the liver (4.1%) and the adrenal gland (6.8%). Median followup was 16.1 months (range 3.5 to 157.1). The local control rate at 12 and 18 months was 90.2% and 90.2%, respectively. The progression-free survival rate at 12 and 18 months was 46.2% (95% CI 32.2-59) and 35% (95% CI 21.4-48.9), respectively. On univariate and multivariable analyses metachronous and single metastases predicted better progression-free survival. Systemic therapy before stereotactic body radiation therapy predicted improved local control in clear cell cases. CONCLUSIONS: Stereotactic body radiation therapy can be considered a safe approach and it provides effective local control of oligometastatic renal cell carcinoma. However, future prospective studies are necessary to evaluate the impact on survival and quality of life.

Phase II trial on SBRT for unresectable liver metastases: long-term outcome and prognostic factors of survival after 5 years of follow-up.

BACKGROUND: The aim of this study was to evaluate long-term efficacy and survival prognostic factors of stereotactic body radiation therapy (SBRT) for un-resectable liver metastases in patients enrolled in a prospective phase II trial. METHODS AND MATERIALS: 5-year local control (LC), overall survival (OS), progression free survival (PFS) and toxicity rates were analyzed in patients with un-resectable liver metastases enrolled in a Phase II Trial on liver SBRT, with a prescription dose of 75Gy in 3 consecutive fractions. RESULTS: A total of 61 patients with 76 lesions were enrolled, with a median follow-up time of 6.1 years. One, three and 5 year LC rates were 94 ± 3.1%, 78.0 ± 5.9% and 78.0 ± 5.9%, without reaching the median LC time. Median OS was 27.6 months and the survival rates were 85.2 ± 4.5%, 31.1 ± 5.9% and 18.0 ± 4.9% at 1, 3 and 5-year after SBRT, respectively. Univariate analysis showed that favorable primary site (colorectal, breast and gynecological) of metastases (p = 0.001) improved survival. Toxicity was moderate. One patient experienced G3 late chest wall pain, which resolved within 1 year from SBRT. No cases of Radiation Induced Liver Disease (RILD) were detected. CONCLUSIONS: Long-term results of this Phase II study suggest the efficacy and safety of SBRT for un-resectable liver metastases after 5-year of follow up. Selection of cases with positive prognostic factors may improve long-term survival of these oligo-metastastic patients and may confirm the role of SBRT as an effective alternative local therapy for liver metastases.

Role of 11C-choline PET/CT in radiation therapy planning of patients with prostate cancer.

BACKGROUND: In the era of image-guided radiotherapy, PET has become an important tool for tumor delineation in several types of cancer. The aim of this study was to evaluate the effect of this imaging modality in treatment planning of a cohort of patients with prostate cancer eligible for radiotherapy. METHODS: From September 2011 to January 2016, 135 consecutive patients (median age 69 years, range: 53-89) were referred to our department for radiation therapy with radical intent (n=28), for postoperative adjuvant (n=13) or salvage treatment (n=50), for re-irradiation (n=19), or for radiotherapy on oligometastases (n=25). Before planning the radiotherapy course, patients were submitted to carbon-11-choline PET (Cho-PET) to confirm the indication to radiotherapy and the irradiation volumes. RESULTS: Among the 135 patients subjected to Cho-PET, the indication to radiotherapy was modified in 66 (48.8%) cases based on the Cho-PET result. In particular, Cho-PET helped to better define the radiotherapy programme in 12 out of 28 (42.8%) patients who were candidates for primary radiation therapy, 33 (52.4%) of 63 patients undergoing adjuvant/salvage radiotherapy, and 21 out of 44 (47.7%) patients with relapsed/metastatic disease. Overall biochemical response is documented by mean and median prostate specific antigen values, which changed from 15.29 to 4.00 ng/ml, respectively, before to mean 4.74 ng/ml and median 0.81 ng/ml after therapy (P=0.05). CONCLUSION: In our series, Cho-PET had a significant effect on radiotherapy planning of patients affected by prostate cancer, determining a change in management in 48.8% of cases, considering all therapeutic indications.

BRCA mutation in breast cancer patients: Prognostic impact and implications on clinical management.

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.

The efficacy of Stereotactic body radiation therapy and the impact of systemic treatments in oligometastatic patients from prostate cancer.

BACKGROUND: Diagnoses of oligometastatic prostate cancer (PC) increased in the recent years thanks to the advancement in imaging and more effective systemic therapies. Here we evaluate the efficacy of Stereotactic Body Radiation Therapy (SBRT) in oligorecurrent and oligoprogressive PC. METHODS: We included patients with a maximum of five metastases diagnosed in a maximum of two target organs. Concomitant treatment with hormonal therapies or chemotherapies was allowed. End points of the present study were the outcome in terms of Local control of treated metastases (LC), out-field progression free survival, overall progression free survival (PFS), and overall survival. RESULTS: We included in the analysis 64 patients treated on 90 metastases. Fifty (78.1%) patients were treated on lymph nodes, 2 (3.1%) patients simultaneously on lymph node and bone while 10 (15.7%) patients on bone only. Lung metastases were treated in 2 (3.1%) patients. Thirty-seven (57.81%) were without androgen deprivation therapy when treated with SBRT. Median follow-up was 15.2 months. Rates of LC at 6-, 12-, and 18- months were 94%, 88%, and 84%, respectively. Oligoprogressive patients compared to oligorecurrent (HR 9.10, P = 0.049) and prolongation of time from diagnosis of metastases to SBRT (HR 1.03, P = 0.047) were associated with worse LC. Median PFS was 6.6 months (range 1.1-42.4). Castration resistant patients experienced worse PFS compared to castration sensitive group (HR 2.12, P = 0.021). CONCLUSIONS: Stereotactic body radiation therapy seems to be an effective treatment for metastases from PC. Prospective trials are necessary to better define selection of patients and to evaluate combination of SBRT and new systemic drugs in castration resistant patients.