Time filter

Source Type

Paolini A.,University of Pavia | Paolini A.,Irccs Policlinico S Matteo Foundation | Pasi F.,University of Pavia | Facoetti A.,National Center for Oncological Hadrontherapy | And 4 more authors.
Anticancer Research | Year: 2011

Background: Several types of cell death can induce the activation of the immune system by releasing factors of damage. Aim: To identify different cell death modalities using U87 glioblastoma cell line after radio-chemotherapy treatments by analyzing the expression of HSP70 after γ-ray irradiation and temozolomide treatment. Materials and Methods: U87 cell line was irradiated with 2, 4, 8, 10 and 20 Gy, treated with 200 μM of temozolomide, or subjected to combined treatments of these. Results: Forty-eight hours after treatment, apoptosis was more prevalent than necrosis, especially after γ-radiation with a somewhat dose-dependent trend. Temozolomide did not seem to induce significant modifications of the pattern of cell death and protein expression. Temozolomide-induced cell death was lower or equal to that obtained with high dose radiotherapy. A low synergism between the two treatments was observed. Conclusion: This cell line showed a marked radioresistance to conventional clinical doses, showing attempts to repair the induced damage, while temozolomide treatment showed no cytotoxic effects.


Alterio D.,Oncology and Radiotherapy Institute | Ansarin M.,Italian National Cancer Institute | Jereczek-Fossa B.A.,Oncology and Radiotherapy Institute | Jereczek-Fossa B.A.,University of Milan | And 13 more authors.
Tumori | Year: 2013

Aims and background. To achieve the goal of organ preservation, both a chemoradiotherapy and a conservative surgical approach can be proposed. The aim of the study was to review all patients treated in our Institute with conservative surgery and postoperative radiotherapy for locally advanced supraglottic tumor. Methods and study design. A retrospective analysis of 32 patients treated between 2000 and 2010 was performed. Overall survival, disease-free survival and late laryngeal toxicity were evaluated. The impact of surgical procedures, radiotherapy characteristics and addition of chemotherapy on late laryngeal toxicity was studied. Results. The median follow-up was 38 months. Overall survival and disease-free survival at 5 years were 73% and 66%, respectively. Three (9%) patients experienced local recurrence (after 22, 25 and 40 months, respectively) and were treated with total laryngectomy. The larynx preservation rate was 93%. Severe treatment-related late laryngeal toxicity (grade 3 and 4 laryngeal edema, laryngeal stenosis, presence of tracheotomy at last follow-up because of treatment-related toxicity, and the need for enteral nutrition) was experienced by 34% of patients. The functional larynx preservation rate was 81%. The statistically significant risk factors for severe late toxicity were: female gender, extension of the surgical procedure, removal of one arytenoid and association with concomitant chemotherapy. Conclusions. We confirmed literature data on the feasibility and efficacy of a surgical organ preservation strategy. However, the high incidence of severe late toxicity requires further studies to improve patient selection and to reduce side effects. Copyright - Il Pensiero Scientifico Editore.


Trott K.-R.,University of Pavia | Trott K.-R.,University College London | Doerr W.,TU Dresden | Facoetti A.,National Center for Oncological Hadrontherapy | And 5 more authors.
Radiotherapy and Oncology | Year: 2012

The normal tissue complication probability (NTCP) models that are currently being proposed for estimation of risk of harm following radiotherapy are mainly based on simplified empirical models, consisting of dose distribution parameters, possibly combined with clinical or other treatment-related factors. These are fitted to data from retrospective or prospective clinical studies. Although these models sometimes provide useful guidance for clinical practice, their predictive power on individuals seems to be limited. This paper examines the radiobiological mechanisms underlying the most important complications induced by radiotherapy, with the aim of identifying the essential parameters and functional relationships needed for effective predictive NTCP models. The clinical features of the complications are identified and reduced as much as possible into component parts. In a second step, experimental and clinical data are considered in order to identify the gross anatomical structures involved, and which dose distributions lead to these complications. Finally, the pathogenic pathways and cellular and more specific anatomical parameters that have to be considered in this pathway are determined. This analysis is carried out for some of the most critical organs and sites in radiotherapy, i.e. spinal cord, lung, rectum, oropharynx and heart. Signs and symptoms of severe late normal tissue complications present a very variable picture in the different organs at risk. Only in rare instances is the entire organ the critical target which elicits the particular complication. Moreover, the biological mechanisms that are involved in the pathogenesis differ between the different complications, even in the same organ. Different mechanisms are likely to be related to different shapes of dose effect relationships and different relationships between dose per fraction, dose rate, and overall treatment time and effects. There is good reason to conclude that each type of late complication after radiotherapy depends on its own specific mechanism which is triggered by the radiation exposure of particular structures or sub-volumes of (or related to) the respective organ at risk. Hence each complication will need the development of an NTCP model designed to accommodate this structure. © 2011 Elsevier Ireland Ltd. All rights reserved.


De Cicco L.,Ospedale di Circolo di Busto Arsizio | Vischioni B.,National Center for Oncological Hadrontherapy | Vavassori A.,Oncology and Radiotherapy Institute | Gherardi F.,Oncology and Radiotherapy Institute | And 10 more authors.
Brachytherapy | Year: 2014

Purpose: We report the experience of the Radiation Oncology Department of the European Institute of Oncology in Milan, Italy, on the adjuvant low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy. Brachytherapy might be useful to improve keloids recurrence rate or reduce keloids treatment side effects instead of external beam radiotherapy. Methods and Materials: Data on 70 consecutive patients treated after complete keloid surgical excision were retrospectively analyzed. First 38 patients and 46 keloids were treated with adjuvant LDR brachytherapy and the following 39 patients and 50 keloids underwent HDR treatment. Median delivered dose of LDR therapy was 16Gy; HDR median dose was 12Gy. Sixty-four keloids (66.7%) were symptomatic at diagnosis with pain, itching, or stress. Results: Fourteen relapses over 46 treated keloids (30.4%) were observed in the LDR group and 19 of 50 keloids (38%) in the HDR group (p=0.521). Recurrence rate was significantly higher in males (p=0.009), in patients younger than 44years (p < 0.0001), for arms, neck, and chest wall anatomic sites (p=0.0001) and for symptomatic keloids (p=0.017). Aesthetic outcome was better in case of larger keloids (>8cm) (p=0.064). Symptomatic relief was achieved in 92% of HDR patients and only 68% of LDR patients (p=0.032). Conclusions: Postoperative brachytherapy is an effective treatment for keloids. In our study, LDR and HDR treatments resulted in similar recurrence rate. Better symptomatic relief was reported in case of HDR treatment compared with the LDR regimen. © 2014 American Brachytherapy Society.


Marvaso G.,Oncology and Radiotherapy Institute | Vischioni B.,National Center for Oncological Hadrontherapy | Jereczek-Fossa B.A.,Oncology and Radiotherapy Institute | Jereczek-Fossa B.A.,University of Milan | And 12 more authors.
Radiologia Medica | Year: 2016

Hadrontherapy has been in constant progress in the past decades. Due to the increasing interest in this field and the spreading of the technique in Italy and worldwide, the Italian Society of Radiation Oncology surveyed (by an online survey) its members regarding their perception of hadrontherapy. The survey outline addressed different items all related to hadrontherapy, such as: demographics (3 items), personal knowledge (5 items), actual use in clinical practice (5 items), and future perspectives and development (5 items). The survey was filled in by 224 radiation oncologists (RO). Among them, 74.6 % were RO with more than 5 years of clinical practice, and only 10.4 % RO in training. Median age was 46 years (range 27–77). 32.24 % admitted average knowledge about heavy particles radiobiology rationale and 32.42 % about the ongoing particle therapy clinical trials. Radioresistant tumors are perceived as—principal indications for carbon ions in 39.3 % of responders, and pediatric malignancies for protons in 37 %. Re-irradiation is highly recommended for 52.2 %. Strikingly, 38.8 % of participating ROs reported that, in the daily clinical practice, approximately less than 1 out of 10 patients asks to be referred for hadrontherapy. On the other side, 35.7 % claimed need for at least 3 up to 5 particle therapy centers in Italy. Overall, the results of the present survey highlight the interest of the Italian RO community for particle therapy among the other radiotherapy technique. Analysis of our results might picture the clinical attitude of the RO community towards hadrontherapy in Italy, and help in promoting targeted initiatives to spread clinical results and knowledge about technical innovations in this field. © 2016 Italian Society of Medical Radiology


PubMed | National Center for Oncological Hadrontherapy, Ospedale di Circolo di Busto Arsizio, Oncology and Radiotherapy Institute, Italian National Cancer Institute and University of Milan
Type: Evaluation Studies | Journal: Brachytherapy | Year: 2014

We report the experience of the Radiation Oncology Department of the European Institute of Oncology in Milan, Italy, on the adjuvant low-dose-rate (LDR) and high-dose-rate (HDR) interstitial brachytherapy. Brachytherapy might be useful to improve keloids recurrence rate or reduce keloids treatment side effects instead of external beam radiotherapy.Data on 70 consecutive patients treated after complete keloid surgical excision were retrospectively analyzed. First 38 patients and 46 keloids were treated with adjuvant LDR brachytherapy and the following 39 patients and 50 keloids underwent HDR treatment. Median delivered dose of LDR therapy was 16Gy; HDR median dose was 12Gy. Sixty-four keloids (66.7%) were symptomatic at diagnosis with pain, itching, or stress.Fourteen relapses over 46 treated keloids (30.4%) were observed in the LDR group and 19 of 50 keloids (38%) in the HDR group (p=0.521). Recurrence rate was significantly higher in males (p=0.009), in patients younger than 44years (p < 0.0001), for arms, neck, and chest wall anatomic sites (p=0.0001) and for symptomatic keloids (p=0.017). Aesthetic outcome was better in case of larger keloids (>8cm) (p=0.064). Symptomatic relief was achieved in 92% of HDR patients and only 68% of LDR patients (p=0.032).Postoperative brachytherapy is an effective treatment for keloids. In our study, LDR and HDR treatments resulted in similar recurrence rate. Better symptomatic relief was reported in case of HDR treatment compared with the LDR regimen.


Pedicini P.,R.Ø.S.A. | Nappi A.,R.Ø.S.A. | Strigari L.,Regina Elena Cancer Institute | Alicia Jereczek-Fossa B.,Ieo European Institute Of Oncology | And 13 more authors.
Radiation Oncology | Year: 2012

Purpose: To investigate the correlation between the expression of Epidermal Growth Factor receptor (EGFr) and the reduction of the effective doubling time (TD) during radiotherapy treatment and also to determine the dose per fraction to be taken into account when the overall treatment time (OTT) is reduced in accelerated radiotherapy of head and neck squamous cell carcinoma (HNSCC).Methods: A survey of the published papers comparing 3-years of local regional control rate (LCR) for a total of 2162 patients treated with conventional and accelerated radiotherapy and with a pretreatment assessment of EGFr expression, was made. Different values of TD were obtained by a model incorporating the overall time corrected biologically effective dose (BED) and a 3-year clinical LCR for high and low EGFr groups of patients (HEGFr and LEGFr), respectively. By obtaining the TD from the above analysis and the sub-sites' potential doubling time (Tpot) from flow cytometry and immunohistochemical methods, we were able to estimate the average TD for each sub-site included in the analysis. Moreover, the dose that would be required to offset the modified proliferation occurring in one day (Dprolif), was estimated.Results: The averages of TD were 77 (27-90)95% days in LEGFr and 8.8 (7.3-11.0)95% days in HEGFr, if an onset of accelerated proliferation TK at day 21 was assumed. The correspondent HEGFr sub-sites' TD were 5.9 (6.6), 5.9 (6.6), 4.6 (6.1), 14.3 (12.9) days, with respect to literature immunohistochemical (flow cytometry) data of Tpot for Oral-Cavity, Oro-pharynx, Hypo-pharynx, and Larynx respectively. The Dprolif for the HEGFr groups were 0.33 (0.29), 0.33 (0.29), 0.42 (0.31), 0.14 (0.15) Gy/day if α = 0.3 Gy-1 and α/β = 10 Gy were assumed.Conclusions: A higher expression of the EGFr leads to enhanced proliferation. This study allowed to quantify the extent of the effect which EGFr expression has in terms of reduced TD and Dprolif for each head and neck sub-site. © 2012 Pedicini et al.; licensee BioMed Central Ltd.


Kessel K.A.,University of Heidelberg | Bougatf N.,University of Heidelberg | Bougatf N.,Heilbronn University of Applied Sciences | Bohn C.,CHILI GmbH | And 10 more authors.
Radiation Oncology | Year: 2012

Background: To establish a common database on particle therapy for the evaluation of clinical studies integrating a large variety of voluminous datasets, different documentation styles, and various information systems, especially in the field of radiation oncology.Methods: We developed a web-based documentation system for transnational and multicenter clinical studies in particle therapy. 560 patients have been treated from November 2009 to September 2011. Protons, carbon ions or a combination of both, as well as a combination with photons were applied. To date, 12 studies have been initiated and more are in preparation.Results: It is possible to immediately access all patient information and exchange, store, process, and visualize text data, any DICOM images and multimedia data. Accessing the system and submitting clinical data is possible for internal and external users. Integrated into the hospital environment, data is imported both manually and automatically. Security and privacy protection as well as data validation and verification are ensured. Studies can be designed to fit individual needs.Conclusions: The described database provides a basis for documentation of large patient groups with specific and specialized questions to be answered. Having recently begun electronic documentation, it has become apparent that the benefits lie in the user-friendly and timely workflow for documentation. The ultimate goal is a simplification of research work, better study analyses quality and eventually, the improvement of treatment concepts by evaluating the effectiveness of particle therapy. © 2012 Kessel et al.; licensee BioMed Central Ltd.


Iannalfi A.,National Center for Oncological Hadrontherapy | Fragkandrea I.,Royal Marsden NHS Foundation Trust | Brock J.,University of Sussex | Saran F.,Royal Marsden NHS Foundation Trust
Clinical Oncology | Year: 2013

The optimal management of craniopharyngioma remains controversial. Although aggressive (i.e. attempted macroscopic complete/radical) primary surgery can be associated with significant morbidity and a noticeable recurrence rate, a conservative (limited) surgical approach followed by radiotherapy has increasingly been adopted after reports of excellent local control and a significant reduction in the incidence of complications by most multidisciplinary teams. A literature review from January 1990 to May 2012 was carried out identifying 43 studies with 1716 patients treated with irradiation for craniopharyngioma. The outcome and treatment-related toxicity were analysed in relation to the timing of radiotherapy, the target volume definition and radiotherapy dose and compared with the results of radical surgery. For patients undergoing limited surgery and postoperative radiotherapy, reported 10 year local control rates ranged between 77 and 100% and 20 year overall survival was reported as high as 66-92%. Comparable progression-free survival and overall survival were reported for radiotherapy delivered at first diagnosis or at progression. Long-term toxicity of combined limited surgery and irradiation seems to be less than that associated withradical surgery. The total recommended dose prescription to achieve long-term control while minimising adverse sequelae is 50-54Gy delivered withconventional fractionation. Care should be provided by a multidisciplinary team in a specialised centre. However, national and international prospective co-operative trials are warranted to provide robust data to define an internationally multidisciplinary accepted risk-based management strategy. © 2013 The Royal College of Radiologists.


Orlandi E.,Fondazione IRCCS Instituto Nazionale dei Tumori | Iacovelli N.A.,Fondazione IRCCS Instituto Nazionale dei Tumori | Bonora M.,National Center for Oncological Hadrontherapy | Cavallo A.,Fondazione IRCCS Instituto Nazionale dei Tumori | And 2 more authors.
Oral Oncology | Year: 2016

Salivary gland cancers (SGCs) are rare diseases and their treatment depends upon histology, stage and site of origin. Radical surgery is the mainstay of treatment but radiotherapy (RT) plays a key role in both the postoperative and the inoperable setting, as well as in recurrent disease. In the absence of prospective randomized trials, a wide retrospective literature suggests postoperative RT (PORT) in patients with high risk pathological features.SGCs, and adenoid cystic carcinoma (ACC) in particular, are known to be radio-resistant tumors and should therefore respond well to particle beam therapy. Recently, excellent outcome has been reported with radical carbon ion RT (CIRT) in particular for ACC. Both modern photon- and hadron-based treatments are effective and are characterized by a favourable toxicity profile. But it is not clear whether one modality is superior to the other for disease control, due to the differences in patients' selection, techniques, fractionation schedules and outcome measurements among clinical experiences.In this paper, we review the role of photon and particle RT for malignant SGCs, discussing the difference between modalities in terms of biological and technical characteristics. RT dose and target volumes for different histologies (ACC versus non-ACC) have also been taken into consideration. © 2016.

Loading National Center for Oncological Hadrontherapy collaborators
Loading National Center for Oncological Hadrontherapy collaborators