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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. Source

Pedicini P.,R.O.S.A. | Nappi A.,R.O.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. Source

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. Source

Dokic I.,German Cancer Research Center | Dokic I.,Heidelberg Ion Therapy Center | Dokic I.,Heidelberg Institute of Radiation Oncology | Niklas M.,German Cancer Research Center | And 22 more authors.
Frontiers in Oncology | Year: 2015

Development of novel approaches linking the physical characteristics of particles with biological responses are of high relevance for the field of particle therapy. In radiobiology, the clonogenic survival of cells is considered the gold standard assay for the assessment of cellular sensitivity to ionizing radiation. Toward further development of next generation biodosimeters in particle therapy, cell-fluorescent ion track hybrid detector (Cell-FIT-HD) was recently engineered by our group and successfully employed to study physical particle track information in correlation with irradiation-induced DNA damage in cell nuclei. In this work, we investigated the feasibility of Cell-FIT-HD as a tool to study the effects of clinical beams on cellular clonogenic survival. Tumor cells were grown on the fluorescent nuclear track detector as cell culture, mimicking the standard procedures for clonogenic assay. Cell-FIT-HD was used to detect the spatial distribution of particle tracks within colony-initiating cells. The physical data were associated with radiation-induced foci as surrogates for DNA double-strand breaks, the hallmark of radiation-induced cell lethality. Long-term cell fate was monitored to determine the ability of cells to form colonies. We report the first successful detection of particle traversal within colony-initiating cells at subcellular resolution using Cell-FIT-HD. © 2015 Dokic, Niklas, Zimmermann, Mairani, Seidel, Krunic, Jäkel, Debus, Greilich and Abdollahi. Source

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. Source

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