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Background: Treatment for locally advanced differentiated thyroid cancer is surgery followed by radioiodine while the role of adjuvant external beam radiotherapy (EBRT) is debated., Methods: The panel of the Italian Association of Radiotherapy and Clinical Oncology developed a clinical recommendation on the addition of EBRT to radioiodine after surgery for locally advanced differentiated thyroid cancer by using the Grades of Recommendation, Assessment, Development, and Evaluation methodology and the Evidence to Decision framework. A systematic review with meta-analysis about this topic was conducted with a focus on outcome of benefits and toxicity., Results: Locoregional control was improved by EBRT while no considerable toxicity impact was reported., Conclusion: The panel judged uncertain the benefit/harms balance; final recommendation was conditional both for EBRT + radioiodine and radioiodine alone in the adjuvant setting.

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

The therapeutic approach to thyroid carcinoma usually involves surgery as initial treatment. The use of external beam radiotherapy (EBRT) is limited to high-risk patients and depends on clinical stage and histologic type. Different behavior patterns and degrees of aggressiveness of thyroid carcinomas require different management for differentiated, medullary, and anaplastic carcinoma. However, the role of EBRT is an issue of debate. Most clinical studies are retrospective and based on single-institution experiences. In this article, we review the main literature and give recommendations for the use of EBRT in thyroid carcinoma on behalf of the "Radioterapia Metabolica" Group of the Italian Radiation Oncology Association.

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

Aims and Background: Small cell lung cancer is an aggressive histologic subtype of lung cancer in which the role of chemotherapy and radiotherapy has been well established in limited-stage disease. We retrospectively reviewed a series of limited-stage small cell lung cancers treated with chemotherapy and thoracic and brain radiotherapy., Methods and Study Design: A total of 124 patients affected by limited-stage small cell lung cancer has been treated over 10 years in our Institute. Fifty-three patients (42.8%) had concomitant radio-chemotherapy treatment and 71 patients (57.2%) a sequential treatment. Eighty-eight patients (70.9%) underwent an association of a platinum-derived drug (cisplatinum or carboplatinum) and etoposide. Prophylactic cranial irradiation was planned in all patients with histologically proven complete response to primary radio-chemotherapy., Results: With a mean follow-up of 2.2 years, complete response was obtained in 50.8% of cases. We found a significant difference between different radio-chemotherapy association approaches (P = 0.007): percentages of overall survival were respectively 10.0%, 12.9% and 5.6% in early, late concomitant and sequential radio-chemotherapy timing. Cranial prophylaxis did not seem to influence overall survival (P = 0.21) or disease-free survival for local relapse (P = 0.34)., Conclusions: Concomitant radio-chemotherapy is the best approach according to our experience. Our results show a benefit of prophylactic cranial irradiation in distant metastasis-free survival.

Aims and Background: In 2002, a survey including 1759 patients treated from 1980 to 1998 established a "benchmark" Italian data source for prostate cancer radiotherapy. This report updates the previous one., Methods: Data on clinical management and outcomes of 3001 patients treated in 15 centers from 1999 through 2003 were analyzed and compared with those of the previous survey., Results: Significant differences in clinical management (-10% had abdominal magnetic resonance imaging; +26% received ≥70 Gy, +48% conformal radiotherapy, -20% pelvic radiotherapy) and in G3-4 toxicity rates (-3.8%) were recorded. Actuarial 5-year overall, disease-specific, clinical relapse-free, and biochemical relapse-free survival rates were 88%, 96%, 96% and 88%, respectively. At multivariate analysis, D'Amico risk categories significantly impacted on all the outcomes; higher radiotherapy doses were significantly related with better overall survival rates, and a similar trend was evident for disease-specific and biochemical relapse-free survival; cumulative probability of 5-year late G1-4 toxicity was 24.8% and was significantly related to higher radiotherapy doses (P <0.001)., Conclusions: The changing patterns of practice described seem related to an improvement in efficacy and safety of radiotherapy for prostate cancer. However, the impact of the new radiotherapy techniques should be prospectively evaluated.

Aims and background. To report the clinical outcome of linac-based or robotic, image-guided stereotactic body radiotherapy in patients affected by abdominal lymph node metastases from different primary cancers. Methods and methods. Twenty-six patients with 32 abdominal lymph node metastases were consecutively treated at the University of Florence between April 2011 and May 2012. The mean follow-up was 4.6 months (SD, 3.9; range, 0.3-13). The dose prescription ranged between 24 Gy and 36 Gy delivered in 1-5 fractions. Results. In terms of local control, complete response to stereotactic body radiotherapy was obtained in 18 cases (66.7%), partial response in 7 (25.9%), and stable disease in 2 (7.4%). At the Cox univariate regression analysis, an increased risk of partial response or absence of local response to radiotherapy was found for subjects of the female sex (P = 0.036), age less than 50 years (P = 0.022), primary tumor of the genital tract (P = 0.007), and previous chemotherapy (P = 0.057). An excellent local control rate (90.9%) was obtained in patients affected by abdominal lymph node metastases of prostatic origin. Conclusions. Stereotactic body radiotherapy for abdominal lymph node metastases is a safe and effective treatment in terms of high rates of local control, especially in a subset of patients affected by prostate cancer.

Aims and Background: Waiting time for radiotherapy is a major problem in clinical practice. We developed a model to create a priority list of patients waiting for radiotherapy according to clinical criteria, where booking of patients is not on a "first-come, first-served" basis and where prioritization has not been left up to individual discretion., Methods: The system is based on an algorithm that assigns to each patient a personal code (priority code, PC) that can be used as a continuous variable to have a priority list. PCpatient = D0patient + PWTsubgroup of treatment. Palliative treatments were categorized according to the clinical urgency. Radical treatments were stratified by primary tumors, by the setting of treatment (preoperative, curative, postoperative) and by the main prognostic factors. Each subgroup of patients has a "priority waiting time" (PWT subgroup of treatment). Calculation of the PC starts from a differentiated date according to clinical scenario [Reference date (D0)], which is taken from the clinical history of the patient., Results: Patients are differentiated according to clinical criteria and according to time elapsed from diagnosis. The priority list can be automatically updated day by day. Delays in patient referral or imaging availability are minimized., Conclusions: The model represents a tool for an objective and automatic prioritization of the patients who are waiting for radiotherapy.

Noninvasive cellular imaging allows the tracking of grafted cells as well as the monitoring of their migration, suggesting potential applications to track both cancer and therapeutic stem cells. Cell tracking can be performed by two approaches: direct labeling (cells are labeled with tags) and indirect labeling (cells are transfected with a reporter gene and visualized after administration of a reporter probe). Techniques for in vivo detection of grafted cells include optic imaging, nuclear medicine imaging, magnetic resonance imaging, microCT imaging and ultrasound imaging. The ideal imaging modality would bring together high sensitivity, high resolution and low toxicity. All of the available imaging methods are based on different principles, have different properties and different limitations, so several of them can be considered complementary. Transfer of these preclinical cellular imaging modalities to stem cells has already been reported, and transfer to clinical practice within the next years can be reasonably considered.

Aims and Background: Concomitant radio-chemotherapy improves survival of patients with locally advanced non-small cell lung cancer, with a better local-regional control., Methods and Study Design: We report our experience with vinorelbine-based chemotherapy in neoadjuvant and radical settings in 43 patients. Regimens consisted of cisplatin plus vinorelbine in 74.4% patients and carboplatin plus vinorelbine in 14.0%; 11.6% underwent mono-chemotherapy with oral vinorelbine. We estimated the crude probability of death or local recurrence by the Kaplan-Meier method. Cox regression models were used to identify the main significant predictors of death or local recurrence., Results: A significant effect of the response to treatment was shown on both local disease free-survival (P = 0.004) and overall survival (P <0.0001). Patients with progressive disease after primary treatment had a significantly higher risk of further relapse at both univariate (P = 0.046) and multivariate regression analysis (P = 0.014) than patients with a complete response. They also showed a significantly higher risk of death at both univariate (P = 0.0005) and multivariate regression analysis (P <0.0001) than patients with a complete response. The most common toxicity was hematologic and gastroenteric. We recorded grade III/IV leukopenia in 11%, anemia in 6%, and esophagitis in 14% of the patients., Conclusions: Our experience showed that vinorelbine-based chemotherapy is an effective and safe regimen, in association with a platinum compound and thoracic radiotherapy.

Aims and Background: Small cell lung cancer is characterized by an aggressive clinical course and a high sensitivity to both chemotherapy and radiotherapy. We present the Florence University experience in concurrent early radio-chemotherapy in patients affected by limited-stage small cell lung cancer, with particular emphasis on treatment safety, disease outcome and prognostic factors., Methods and Study Design: Fifty-seven patients were treated between June 2000 and February 2005. All patients underwent platinum-based chemotherapy, administered intravenously following two different regimens, for at least three cycles. Eighteen patients (31.6%) received epirubicin and ifosfamide in 3-week cycles alternating with etoposide and cisplatin, administered on day 1 to 3; 39 patients (68.4%) received etoposide and cisplatin. A total of 6 cycles were planned. Radiotherapy was administered concurrently to the first cycle of etoposide and cisplatin., Results: Clinical stage (P = 0.036) and number of chemotherapy courses (P = 0.009) emerged as the only significant death predictors at univariate analysis. Number of chemotherapy courses persisted as a significant death predictor also at multivariate regression analysis, with a reduced death risk for 5-6 chemotherapy cycles in comparison to 3-4 cycles (hazard ratio, 0.44). At a mean follow up of 38.5 months (standard deviation, 3.24 years; range, 6-164 months), considering the best overall tumor response achieved at any time during the whole treatment period, we obtained 32 complete responses (56.1%), 23 partial responses (40.3%) and 2 stable diseases., Conclusions: Our analysis showed that concurrent early radio-chemotherapy in limited-stage small cell lung cancer treatment represents a safe and effective approach in patients. We confirmed the relevant impact on overall survival of effective chemotherapy delivery.

Aims and Background: Anthracyclines such as doxorubicin play a central role in the management of advanced breast cancer. Unfortunately, the clinical benefits of anthracyclines are limited by cardiotoxicity that can lead to the development of potentially fatal congestive heart failure. In order to limit anthracycline-related cardiotoxicity, liposomal formulations of doxorubicin have been developed. This retrospective analysis evaluated the experience obtained with non-pegylated liposomal doxorubicin as first-line therapy in 34 patients with metastatic breast cancer., Methods: Patients received non-pegylated liposomal doxorubicin in combination with either cyclophosphamide (n = 14) or docetaxel (n = 20) for up to eight cycles, and efficacy and safety were assessed according to standard criteria., Results: The overall response rate was 71%. The median progression-free survival was 8 months in patients receiving non-pegylated liposomal doxorubicin plus cyclophosphamide and 13.8 months in those receiving non-pegylated liposomal doxorubicin plus docetaxel (P = 0.2). The most commonly observed toxicities were grade 1-2 leucopenia, alopecia, nausea and vomiting; no grade 3-4 toxicities were observed. Overall, three patients (9%) experienced grade 1 cardiac toxicity., Conclusions: Our results support the use of non-pegylated liposomal doxorubicin as an alternative to conventional doxorubicin formulations in combination regimens for the first-line therapy of metastatic breast cancer.