Nicola Dinapoli

Abstract: BACKGROUND AND PURPOSE: In vitro radiation doses of below 0.5 Gy have been shown to be more effective than higher doses per unit dose in killing clonogenic cells of many epithelial tumor cell lines. This phenomenon is known as low-dose hyperradiosensitivity. Preclinical studies have now suggested that there is synergism between chemotherapy and low-dose fractionated radiotherapy (LD-FRT). To test the clinical efficacy of this approach, we prospectively evaluated concurrent palliative chemotherapy and LD-FRT in patients with various types of epithelial tumors. METHODS AND MATERIALS: Patients suffering from relapses or metastases of epithelial tumors were scheduled to receive concurrent LD-FRT (two fractions of 0.4 Gy per day) and chemotherapy. Radiologic assessments were performed after three cycles of chemotherapy plus LD-FRT. RESULTS: Between June 2006 and October 2007, 12 patients with lung cancer, 7 patients with head-and-neck tumors, 2 patients with breast cancer, and 1 patient with esophageal carcinoma, for a total patient population of 22, underwent concomitant LD-FRT and chemotherapy. All patients but 3 (86%) had received previous treatments for their cancer. The median total dose of LD-FRT delivered was 800 cGy (range, 320-1280 cGy). The overall response rate was 45% (42% in previously treated patients). Grade 3-4 hematologic toxicities (Radiation Therapy Oncology Group ratings) were observed in 2 patients. At a median follow-up of 6.5 months, however, no local toxicity was observed. CONCLUSION: In our experience, concurrent LD-FRT and chemotherapy was well tolerated. Because the response rate seems promising, prospective Phase II studies of the strategy are now under way.

Abstract: BACKGROUND AND PURPOSE: A systematic review and meta-analysis was performed to assess the impact of radiotherapy on both 3- and 5-year survival in patients with resectable gastric cancer. METHODS: Randomized Clinical Trials (RCTs) in which radiotherapy, (preoperative, postoperative and/or intraoperative), was compared with surgery alone or surgery plus chemotherapy in resectable gastric cancer were identified by searching web-based databases and supplemented by manual examination of reference lists. Meta-analysis was performed using Risk Ratios (RRs). Random or fixed effects models were used to combine data. The methodological quality was evaluated by Chalmers' score. RESULTS: Radiotherapy had a significant impact on 5-year survival. Using an intent to treat (ITT) and a Per Protocol (PP) analysis, the overall 5-year RR was 1.26 (95% CI: 1.08-1.48; NNT=17) and 1.31 (95% CI: 1.04-1.66; NNT=13), respectively. Although the quality of the studies was variable, the data were consistent and no clear publication bias was found. CONCLUSION: This meta-analysis showed a statistically significant 5-year survival benefit with the addition of radiotherapy in patients with resectable gastric cancer. Radiotherapy remains a standard component in the treatment of resectable gastric cancer and new RCTs need to address the impact of new conformal radiotherapy technologies.

Abstract: AIMS AND BACKGROUND: The aim of the study was to analyze the feasibility of a setting up of a radiotherapy department using videoconferencing technology. MATERIAL AND METHODS: A videoconferencing network was started to link an academic center of radiotherapy to a peripheral center of research at the start of its activity. Two years of data of involved professionals, subjects of links, audio, video link problems and running costs were recorded. RESULTS: A total of 418 links was established for an overall duration of 458 hours. The participants included all departmental staff. Videoconferencing involved teaching, ward organization, medical care and scientific subjects. In the second year ofexperience, the number of videoconferencing links was higher than the first (232 vs 186). Link times were reasonable for both skilled and unskilled operators. Overall, the cost per minute of link was 0.2 Euro, and the mean cost per link was 13 Euros. Videoconferencing was integrated with fax and computer networks to enhance sharing paper and electronic documents. Audio-video technical problems progressively decreased: the link was definitively interrupted or its activation unfeasible in only 1.0% of cases. CONCLUSIONS: Our experience suggests that the establishment of a link between radiotherapy departments addressed to these aims is feasible by a videoconferencing network.

Abstract: The radiation-induced cardiovascular pathology represents a major cause of morbidity and mortality in patients undergoing therapeutic chest irradiation. There is a broad range of clinical manifestations probably associated with dose, volume and technique of irradiation. From the assumption that prevention is the best way to manage radiation-induced cardiotoxicity, based on the pathophysiogenesis of heart structures, a number of reports of the literature are reviewed. They consider the incidence of cardiovascular disease in patients affected by Hodgkin's lymphoma and breast cancer. The dosimetric prevention is takled in terms of therapeutic procedures and doses (IMRT, 3DCRT) with particular reference to the impact on cardiotoxicity of parameters as maximum heart distance (MHD), mean lung dose (MLD), normal tissue complication probability (NTCP) and V30. The different evaluation criteria of cardiotoxicity are reported, based on the review of the major scoring scales of acute and late complications, which have been worked out in the course of time (LENT-SOMA, RTOG, CTC v.2.0 and CTC v.3.0). The monitoring system of late toxicity used by the authors is presented.

Abstract: Radiotherapy still plays a major role in the treatment of brain lesions. Its end-points are not only better survival but especially better disease control that positively impacts on better quality of life. However radiotherapy is not free of both acute and late side-effects. Data on late toxicity are disappointing, for inadequate follow-up time and the absence of cards for collecting information shared by the scientific community in an attempt to acheive a common, universal language. While these treatments should be considered for palliation, the main goal is always the patient with his/her quality of life, and their toxicity should be monitored to optimize therapeutic outcomes and lower the incidence of complications. The monitoring system of late toxicity used by the authors is presented.

Abstract: BACKGROUND AND PURPOSE: Three-dimensional conformal radiotherapy and intensity modulated radiotherapy allow accurate dose delivery on target volumes. Due to the different background among specialists involved in target volume definition, the contouring emerges as one of the most questionable steps in treatment planning procedures. A software tool devoted to contouring training, named tutorial for image guided external radiotherapy ('TIGER'), based on the Visible Human Project images data-set, is described. MATERIALS AND METHODS: TIGER is addressed to facilitate the learning of axial anatomical images, to promote the training and reproducibility in contouring process, to allow the availability of a tool to enhance the 'drill and practice' approach in training programs. TIGER includes three different environments: Anatomic tutorial devoted to facilitate a self-learning approach to axial body sections; Contouring tutorial addressed to practice contouring process of anatomical structures and to undergo a test program prepared by tutors; Teacher's tools to offer to tutors the opportunity to insert new outlines in TIGER-database, according to local needs or conventions, and to use them in tutorial programs. TIGER-database is grouped in six main anatomical sections: head and neck, male thorax, female thorax, abdomen, male pelvis, and female pelvis. Overall 432 corresponding CT-VH images and 1189 contours of 134 different anatomical structures and lymphatic drainage areas are available. The access to the TIGER software is allowed by ESTRO web site (http://www.estro.be). CONCLUSIONS: TIGER provides an interactive human anatomy cross-sectional oriented source to facilitate the interpretation of CT scan images usually contoured in daily practice. It offers a drill tool to facilitate the learning of a reproducible contouring procedure.

Abstract: Unplanned gaps in radiotherapy can impact on its clinical effect, especially in tumors with accelerated repopulation. In the literature, several technical solutions have been proposed. According to the situation, compensation for the effect on the tumor to the detriment of normal tissue tolerance can be achieved. An approach, modulated according to the gap duration and timing is proposed aimed at constant tumor control with no significant increased risk of side-effects. The decisional algorithm and calculation formulae are used in our center in teaching addressed to residents to make them familiar with the possible clinical applications of radiobiological knowledge.

Abstract: Despite the low local recurrence rate that can be achieved by adequate surgery (total mesorectal excision--TME), radiation therapy was shown to play a significant role in reducing this risk. The widespread use of TME in many European Centers has introduced a new terminology and the need to identify the area at major risk for local failure using this surgical procedure. In the surgical series where extended extra-mesorectal surgery was performed, the role of lymphatic spread was evidenced, especially for low rectal cancer, through the pelvic parietal fascia and lateral pelvic spaces. The aim of this study was to better define some anatomic concepts and the main risk factors which impact on CTV contouring and field conformation in rectal cancer treatment. This information helps formulating guidelines for CTV contouring in daily radiotherapy practice, in order to define the best therapy, according to the tumor stage and location.

Abstract: Elderly age is one of the main risk factors to be associated with the onset of different tumors. The tumor in the elderly almost always appears at a late, advanced stage for the lack of an accurate attention to symptoms-signs, as well as for the absence of involvement in mass screening campaigns. In the choice of a radiotherapy treatment in the elderly, the healthy tissues adjacent to the tumor may show a different ability for repair; this should be kept in mind in the definition of the target volume together with the possible presence of comorbidities specific to the elderly age.

Abstract: In the last two decades there was a radical change in radiotherapy setup. The growing availability of CT equipment and console for computer-aided treatment planning setup enabled the use of advanced technologies as conformal 3D radiation therapy in most centers. In particular in 1987 virtual simulation was proposed for setup. During its use a number of application modalities appeared. Virtual simulation in some centers is applied alone while in others it is associated with conventional simulation. However, from numerous reports published in last years it seems that virtual simulation significantly improves treatment quality independently of radical or palliative intent and of the size of treated volumes (high doses to small volumes or wide shaped fields). Some studies stressed that virtual simulation could significantly shorten treatment planning times with consequent cost reduction. The use of virtual simulation evidenced associated problems and in particular setup limitations due to the CT gantry size, the need to up-date the conventional modalities of setup verification according to the new technologies and more generally to up-date quality assurance procedures in an advanced technological setting. Finally there was the self-evident need of a better knowledge of the anatomy on axial sections, of tumor spread routes in particular.

Abstract: PURPOSE: Conformal therapy of prostate cancer is based on high-dose irradiation to the entire prostate gland. The aim of this study was to analyze the pattern of intraprostatic recurrence in patients undergoing external beam radiotherapy (EBRT) at a dose of 65-70 Gy to evaluate whether conventional radiotherapy doses are adequate to control microscopic disease outside the primary tumor and therefore whether high-dose irradiation can be exclusively focused on the macroscopic disease. METHODS AND MATERIALS: The clinical and radiologic reports of 118 patients with prostate cancer undergoing EBRT (64.8-70.2 Gy) combined with hormonal therapy were evaluated. In all patients, before and after therapy, the size and site of the primary neoplasm within the prostate were assessed by clinical examination and imaging studies. RESULTS: With a median follow-up of 45 months (range 14-119), the 5-year actuarial local control rate was 83.9%. Twelve patients had an intraprostatic recurrence, with the appearance of a new nodule (in 5 patients with a complete response after therapy) or increased nodular size compared with the minimal size (in the 7 other patients). In all patients, on the basis of a semiquantitative evaluation of the site of recurrence, this was shown to originate within the initial tumor volume. CONCLUSION: The results of this analysis seem to confirm some histologic findings observed in patients undergoing prostatectomy for local recurrence after radiotherapy that suggest that local recurrence usually originates in the primary tumor rather than in focal prostatic intraepithelial neoplasia. This observation might justify the application of conformal therapy procedures aimed at identifying the gross tumor volume, in the phase of boost, exclusively with the primary tumor.