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2. Cellular and molecular effects of protons: Apoptosis induction and potential implications for cancer therapy

Author

Di Pietro, C., Piro, S., Tabbì, G., Ragusa, M., Di Pietro, V., Zimmitti, V., Cuda, F., Anello, M., Consoli, U., Salinaro, E. T., Caruso, M., Vancheri, C., Crimi, N., Sabini, M. G., Cirrone, G. A. P., Raffaele, L., Privitera, G., Pulvirenti, A., Giugno, R., Ferro, A., Cuttone, G., Nigro, S. Lo, Purrello, R., Purrello, F., and Purrello, M.

Published
2006
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3. An enhanced random walk algorithm for delineation of head and neck cancers in PET studies

Author

Stefano, A, Vitabile, S, Russo, G, Ippolito, M, Sabini, M, Sardina, D, Gambino, O, Pirrone, R, Ardizzone, E, Gilardi, M, Stefano A., Vitabile S., Russo G., Ippolito M., Sabini M. G., Sardina D., Gambino O., Pirrone R., Ardizzone E., Gilardi M. C., Stefano, A, Vitabile, S, Russo, G, Ippolito, M, Sabini, M, Sardina, D, Gambino, O, Pirrone, R, Ardizzone, E, Gilardi, M, Stefano A., Vitabile S., Russo G., Ippolito M., Sabini M. G., Sardina D., Gambino O., Pirrone R., Ardizzone E., and Gilardi M. C.

Abstract

An algorithm for delineating complex head and neck cancers in positron emission tomography (PET) images is presented in this article. An enhanced random walk (RW) algorithm with automatic seed detection is proposed and used to make the segmentation process feasible in the event of inhomogeneous lesions with bifurcations. In addition, an adaptive probability threshold and a k-means based clustering technique have been integrated in the proposed enhanced RW algorithm. The new threshold is capable of following the intensity changes between adjacent slices along the whole cancer volume, leading to an operator-independent algorithm. Validation experiments were first conducted on phantom studies: High Dice similarity coefficients, high true positive volume fractions, and low Hausdorff distance confirm the accuracy of the proposed method. Subsequently, forty head and neck lesions were segmented in order to evaluate the clinical feasibility of the proposed approach against the most common segmentation algorithms. Experimental results show that the proposed algorithm is more accurate and robust than the most common algorithms in the literature. Finally, the proposed method also shows real-time performance, addressing the physician’s requirements in a radiotherapy environment.

Published
2017

4. Correlation between histological grade and positron emission tomography parameters in cervical carcinoma

Author

Mocciaro, V, Scollo, P, Stefano, A, Gieri, S, Russo, G, Scibilia, G, Cosentino, S, Mure, G, Baldari, S, Sabini, M, Fraggetta, F, Gilardi, M, Ippolito, M, Mocciaro V., Scollo P., Stefano A., Gieri S., Russo G., Scibilia G., Cosentino S., Mure G., Baldari S., Sabini M. G., Fraggetta F., Gilardi M. C., Ippolito M., Mocciaro, V, Scollo, P, Stefano, A, Gieri, S, Russo, G, Scibilia, G, Cosentino, S, Mure, G, Baldari, S, Sabini, M, Fraggetta, F, Gilardi, M, Ippolito, M, Mocciaro V., Scollo P., Stefano A., Gieri S., Russo G., Scibilia G., Cosentino S., Mure G., Baldari S., Sabini M. G., Fraggetta F., Gilardi M. C., and Ippolito M.

Abstract

The aim of the present study was to evaluate the changes in cervical cancer glucose metabolism for different levels of cellular differentiation. The metabolic activity was measured by standardized uptake value (SUV), SUV normalized to lean body mass, metabolic tumor volume and total lesion glycolysis using fluorine-18 fluorodeoxyglucose positron emission tomography (PET). A correlation study of these values could be used to facilitate therapeutic choice and to improve clinical practice and outcome. This study considered 32 patients with diagnosed cervical cancers, at different International Federation of Gynecology and Obstetrics stages. Glucose metabolism was assessed by PET examination, and histological specimens were examined to determine their initial grade of differentiation. A correlation study of these values was evaluated. Histological examination showed that all cases were of squamous cell carcinoma. Regarding the differentiation of the tumor, 19 well- to moderately-differentiated tumors and 13 poorly-differentiated tumors were determined. Negative findings for correlations between metabolic parameters and initial grade of histological differentiation were found, and considering that histological grade has been shown to have no consistent prognostic value in cervical cancer treatment, PET imaging could play a significant role in cervical cancer prognosis.

Published
2016

5. Evaluation of erlotinib treatment response in non-small cell lung cancer using metabolic and anatomic criteria

Author

Stefano A. 1, 2, Russo G. 1, Ippolito M. 3, Cosentino S. 3, Murè G. 3, Baldari S. 3, Sabini M. G. 4, Sardina D. 4, Valastro L.M. 4, Bordonaro R. 5, Messa C. 1, 6, Gilardi M.C. 1, and Soto Parra H. 7

Subjects
neoplasms
Abstract

AIM: In this paper the clinical value of PET for early prediction of tumor response to Erlotinib in patients with advanced or metastatic nonsmall cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen is evaluated. The aim was to compare the early metabolic treatment response using European Organization for Research and Treatment of Cancer (EORTC) 1999 recommendations and PET Response Criteria in Solid Tumors (PERCIST), and the standard treatment response using Response Evaluation Criteria in Solid Tumors (RECIST). METHODS: Twenty patients with stage IV NSCLC were enrolled prospectively. PET/CT studies were performed before, then 48 h, and 45 days after the initiation of Erlotinib treatment. The lesion with the highest uptake in each patient was evaluated according to EORTC 1999 recommendations, PERCIST and RECIST to assess metabolic and anatomic response. Response classifications were compared statistically using Wilcoxon signedrank test. Disease-Free Survival (DFS) and Overall Survival (OS) were calculated by the KaplanMeier test. RESULTS: At 48 h, the KaplanMeier analysis showed that EORTC proved to be a significant prognostic factor for predicting DFS and OS. At 45 days, there was a significant difference in response evaluation between RECIST and metabolic classifications. RECIST and PERCIST were significant prognostic factors for predicting DFS and OS. EORTC was not able to discriminate responder from non-responder patients. CONCLUSION: This study shows that, according to the EORTC protocol, the PET exam is able to provide early identification of patients who benefit from Erlotinib treatment. Used at the end of therapy, PERCIST could be considered an appropriate metabolic evaluation method to discriminate responders from nonresponders.

Published
2014

6. Metabolic response assessment in non-small cell lung cancer patients after platinum-based therapy: A preliminary analysis

Author

Stefano, A, Porcino, N, Banna, G, Russoa, G, Mocciaro, V, Anile, G, Gieri, S, Cosentino, S, Mure, G, Baldari, S, Sabini, M, Sardina, D, Fraggetta, F, Vitabile, S, Gilardi, M, Ippolito, M, Stefano A., Porcino N., Banna G., Russoa G., Mocciaro V., Anile G., Gieri S., Cosentino S., Mure G., Baldari S., Sabini M. G., Sardina D., Fraggetta F., Vitabile S., Gilardi M. C., Ippolito M., Stefano, A, Porcino, N, Banna, G, Russoa, G, Mocciaro, V, Anile, G, Gieri, S, Cosentino, S, Mure, G, Baldari, S, Sabini, M, Sardina, D, Fraggetta, F, Vitabile, S, Gilardi, M, Ippolito, M, Stefano A., Porcino N., Banna G., Russoa G., Mocciaro V., Anile G., Gieri S., Cosentino S., Mure G., Baldari S., Sabini M. G., Sardina D., Fraggetta F., Vitabile S., Gilardi M. C., and Ippolito M.

Abstract

The purpose of this study was to evaluate the clinical value of PET (Positron Emission Tomography) for early prediction of tumor response to platinum-based therapy in patients with nonsmall cell lung cancer (NSCLC). The evaluation was carried out comparing the standard treatment response using RECIST (Response Evaluation Criteria in Solid Tumors) with metabolic treatment response according to European Organization for Research and Treatment of Cancer (EORTC) recommendations, PET Response Criteria in Solid Tumors (PERCIST), Total Lesion Glycolysis (TLG) and Metabolic Tumor Volume (MTV). Seventeen inoperable patients with stage IV NSCLC were enrolled between October 2011 and June 2013: PET studies were carried out before the initiation of platinum-based therapy and after the first cycle of chemotherapy for an early therapy monitoring. The lesions with the highest uptake in each patient were evaluated according to EORTC recommendations considering a cut-off of 15% (EORTC15%) and 25% (EORTC25%) to discriminat between patients who respond from those who do not respond to treatment. Moreover, PERCIST and RECIST classifications were evaluated too. Receiver operating characteristic curves were used to obtain cut-off points for therapy evaluation based on variations of TLG and MTV in sequential scans. Overall Survival (OS) time was calculated by the Kaplan-Meier test. The Kaplan-Meier analysis showed that RECIST, EORTC15%, ∆TLG, and ∆MTV proved to be a significant prognostic factor for predicting OS (p-value ≤ 0.0251). For responder patients, median OS was 595 days for RECIST, 423 for EORTC15% and ∆MTV, 492 for ∆TLG. For nonresponder patients, median OS was 238 days for RECIST and ∆TLG, 194.5 for EORTC15%, and 188 for ∆MTV. No statistically significant difference was recognized between responder and non-responder patients according to EORTC25% and PERCIST classifications (p-value ≥ 0.13). In addition, a new threshold of 17% for PERCIST classification was proposed for an earl

Published
2015

7. An automatic method for metabolic evaluation of gamma knife treatments

Author

Murino V.,Puppo E.,Murino V., Stefano, A, Vitabile, S, Russo, G, Ippolito, M, Marletta, F, D'Arrigo, C, D'Urso, D, Sabini, M, Gambino, O, Pirrone, R, Ardizzone, E, Gilardi, M, Stefano A., Vitabile S., Russo G., Ippolito M., Marletta F., D'Arrigo C., D'Urso D., Sabini M. G., Gambino O., Pirrone R., Ardizzone E., Gilardi M. C., Murino V.,Puppo E.,Murino V., Stefano, A, Vitabile, S, Russo, G, Ippolito, M, Marletta, F, D'Arrigo, C, D'Urso, D, Sabini, M, Gambino, O, Pirrone, R, Ardizzone, E, Gilardi, M, Stefano A., Vitabile S., Russo G., Ippolito M., Marletta F., D'Arrigo C., D'Urso D., Sabini M. G., Gambino O., Pirrone R., Ardizzone E., and Gilardi M. C.

Abstract

Lesion volume delineation of Positron Emission Tomography images is challenging because of the low spatial resolution and high noise level. Aim of this work is the development of an operator independent segmentation method of metabolic images. For this purpose, an algorithm for the biological tumor volume delineation based on random walks on graphs has been used. Twenty-four cerebral tumors are segmented to evaluate the functional follow-up after Gamma Knife radiotherapy treatment. Experimental results show that the segmentation algorithm is accurate and has real-time performance. In addition, it can reflect metabolic changes useful to evaluate radiotherapy response in treated patients.

Published
2015

21. Online measurement of fluence and position for protontherapy beams

Author

Benati, C., Boriano, Alberto, Bourhaleb, F., Cirio, Roberto, Cirrone, G. A. P., Cornelius, I., Cuttone, G., Donetti, M., Garelli, elena maria, Giordanengo, Simona, Guerin, L., LA ROSA, Alessandro, Luparia, Andrea, Marchetto, F., Martin, F., Meyroneinc, S., Peroni, Cristiana, Pitta, G., Raffaele, L., Sabini, M. G., and Valastro, L.

Subjects
dosimetry, hadrontherapy, DYNAMIC-RANGE, PERFORMANCES
Published
2004

23. Implementation of a new Monte Carlo simulation tool for the development of a proton therapy beam line and verification of the related dose distributions

Author

Cirrone, G A. P, Cuttone, G, Guatelli, S, Lo Nigro, S, Mascialino, B, Pia, M G, Raffaele, L, Russo, G, Sabini, M G, Cirrone, G A. P, Cuttone, G, Guatelli, S, Lo Nigro, S, Mascialino, B, Pia, M G, Raffaele, L, Russo, G, and Sabini, M G

Abstract

Using the Monte Carlo simulation tool GEANT4 we simulated the hadron-therapy beam line of the CATANA center. CATANA is the unique italian hadron-therapy facility in which 62 AMeV proton beams are used for the radiotherapeutic treatment of choroidal and iris melanomas. All the elements, such as diffusers, range shifters, collimators and detectors, typical of a proton-therapy line were modelled. The CATANA beam line provides an ideal environment for the experimental testing and validation of the software developed. The software architecture was developed, and now the validation of the software is in its final stage. Simulated ranges, energy distribution, depth and lateral dose distributions for full energy proton beams will be compared to the experimental results obtained at LNS with different detectors.

Published
2005

24. Dosimetric and clinical experience in eye proton treatment at INFN-LNS

Author

Cirrone, G. A. P., primary, Cuttone, G., additional, Di Rosa, F., additional, Lojacono, P., additional, Mongelli, V., additional, Lo Nigro, S., additional, Ott, J., additional, Patti, I. V., additional, Pittera, S., additional, Privitera, G., additional, Raffaele, L., additional, Reibaldi, A., additional, Russo, G., additional, Salamone, V., additional, Sabini, M. G., additional, Spatola, C., additional, Valastro, L. M., additional, Jeong, Sun-Chan, additional, Utsuno, Yutaka, additional, Motobayashi, Tohru, additional, and Bracco, Angela, additional

Published
2009
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26. STRIP IONIZATION CHAMBER AS BEAM MONITOR IN THE PROTON THERAPY EYE TREATMENT

Author

MARCHETTO, F., primary, CIRIO, R., additional, GARELLA, M. A., additional, GIORDANENGO, S., additional, BORIANO, A., additional, GIVEHCHI, N., additional, LA ROSA, A., additional, PERONI, C., additional, DONETTI, M., additional, BOURHALEB, F., additional, PITTA', G., additional, CIRRONE, G. A. P., additional, CUTTONE, G., additional, RAFFAELE, L., additional, SABINI, M. G., additional, and VALASTRO, L., additional

Published
2006
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27. TL and TSC solid state detectors in proton therapy.

Author

Cirrone, G. A. P., Sabini, M. G., Bruzzi, M., Bucciolini, M., Cuttone, G., Guasti, A., Lo Nigro, S., Mazzocchi, S., Pirollo, S., Raffaele, L., and Sciortino, S.

Subjects
*PHYSIOLOGICAL effects of radiation, *DETECTORS
Abstract

The necessity to develop methods and techniques for a better determination of absorbed dose in the radiotherapy field stimulates new clinical applications of solid state detectors. In this work we have studied the possibility to use of TLD-100 and synthetic CVD diamond detectors as dosimeters for high-energy proton beams. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Published
2000

28. Use of 70 MeV proton beam for medical applications at INFN-LNS: CATANA project.

Author

Sabini, M. G., Cirrone, G. A. P., Tonghi, L. Barone, Bartolotta, A., Brai, M., Cuttone, G., Nigro, S. Lo, Marano, F., Nicoletti, G. A., Privitera, G., Raffaele, L., Reibaldi, A., Romeo, N., Rovelli, A., Salamone, V., and Teri, G.

Subjects
*SCIENCE projects, *TUMORS, *PROTON therapy
Abstract

The project CATANA (Centro di Adro Terapia ed Applicazioni Nucleari Avanzate) is a collaboration between the INFN-Laboratori Nazionali del Sud (LNS), Physics Department, Ophthalmology Institute and Radiology Institute of the Catania University and CSFNSM Catania. The main goal of CATANA is the study and the application of protontherapy for the treatment of shallow tumors (4 cm max) like uveal melanomas and subfoveal macular degenerations. © 2000 American Institute of Physics. [ABSTRACT FROM AUTHOR]

Published
2000

29. Radiochromic film dosimetry of a low energy proton beam

Author

Piermattei, A., primary, Miceli, R., additional, Azario, L., additional, Fidanzio, A., additional, delle Canne, S., additional, De Angelis, C., additional, Onori, S., additional, Pacilio, M., additional, Petetti, E., additional, Raffaele, L., additional, and Sabini, M. G., additional

Published
2000
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30. Cellular and molecular effects of protons: Apoptosis induction and potential implications for cancer therapy.

Author

Pietro, C., Piro, S., Tabbì, G., Ragusa, M., Di Pietro, V., Zimmitti, V., Cuda, F., Anello, M., Consoli, U., Salinaro, E. T., Caruso, M., Vancheri, C., Crimi, N., Sabini, M. G., Cirrone, G. A. P., Raffaele, L., Privitera, G., Pulvirenti, A., Giugno, R., and Ferro, A.

Subjects
PROTONS, APOPTOSIS, CANCER treatment, ELECTRON paramagnetic resonance, POLYMERASE chain reaction
Abstract

Due to their ballistic precision, apoptosis induction by protons could be a strategy to specifically eliminate neoplastic cells. To characterize the cellular and molecular effects of these hadrons, we performed dose-response and time-course experiments by exposing different cell lines (PC3, Ca301D, MCF7) to increasing doses of protons and examining them with FACS, RT-PCR, and electron spin resonance (ESR). Irradiation with a dose of 10 Gy of a 26,7 Mev proton beam altered cell structures such as membranes, caused DNA double strand breaks, and significantly increased intracellular levels of hydroxyl ions, are active oxygen species (ROS). This modified the transcriptome of irradiated cells, activated the mitochondrial (intrinsic) pathway of apoptosis, and resulted in cycle arrest at the G2/M boundary. The number of necrotic cells within the irradiated cell population did not significantly increase with respect to the controls. The effects of irradiation with 20 Gy were qualitatively as well as quantitatively similar, but exposure to 40 Gy caused massive necrosis. Similar experiments with photons demonstrated that they induce apoptosis in a significantly lower number of cells and in a temporally delayed manner. These data advance our knowledge on the cellular and molecular effects of proton irradiation and could be useful for improving current hadrontherapy protocols. [ABSTRACT FROM AUTHOR]

Published
2006
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31. Implementation of a New Monte Carlo-GEANT4 Simulation Tool for the Development, of a Proton Therapy Beam Line and Verification of the Related Dose Distributions.

Author

Cirrone, G. A. Pablo, Cuttone, G., Guatelli, S., Nigro, S. Lo, Mascialino, B., Pia, M. G., Raffaele, L., Russo, G., and Sabini, M. G.

Subjects
THERAPEUTICS, DIAGNOSTIC imaging, MONTE Carlo method, COMPUTER software, MEDICAL technology, ESTIMATION theory
Abstract

Using the Monte Carlo simulation tool GEANT4, we simulated the hadron-therapy beam line of the Centro di AdroTer- apia ed Applicazioni Nucleari Avanzate (CATANA) center. This is the unique Italian hadron-therapy facility in which 62-MeV proton beams are used for the radiotherapeutic treatment of choroidal and iris melanomas. All the elements, such as diffusers, range shifters, collimators, and detectors, typical of a proton-therapy line were modeled. The beam line provides an ideal environment for the ex- perimental testing and validation of the software developed. The software architecture was developed, and the validation of the soft- ware is in its final stage. Simulated ranges, energy distribution, depth and lateral dose distributions for full energy proton beams will be compared to the experimental results obtained at Laboratori Nazionalidel Sud (LNS) with different detectors. [ABSTRACT FROM AUTHOR]

Published
2005
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35. Dosimetry of clinical proton beams

Author

Raffaele, L., Cirrone, G. A. P., Cirrone, G., Salamone, V., Marino, C., Pittera, S., Lucia Valastro, Lojacono, P. A., Lo Nigro, S., and Sabini, M. G.

43. Evaluation of Platinum-based Therapy Response in Non-Small Cell Lung Cancer

Author

Ippolito, M., Stefano, A., Russo, G., Gieri, S., Cosentino, S., Mure, G., Baldari, S., Sabini, M. G., Fraggetta, F., Salvatore Vitabile, Gilardi, M. C., Banna, G., Ippolito, M, Stefano, A, Russo, G, Gieri, S, Cosentino, S, Mure, G, Baldari, S, Sabini, MG, Fraggetta, F, Vitabile, S, Gilardi, MC, and Banna, G

Subjects
Settore ING-INF/05 - Sistemi Di Elaborazione Delle Informazioni, Lung Cancer, Platinum-based Therapy
Abstract

Aim: To evaluate the clinical value of PET imaging for an early prediction of tumor response to platinum-based therapy in patients with non-small cell lung cancer (NSCLC). In order to avoid unnecessary toxicity of ineffective chemotherapy treatment, an early identification of NSCLC patients who benefit from this therapy is mandatory. Materials and methods: Seventeen patients are enrolled prospectively: 18F-FDG-PET examinations are carried out before treatment and after the first course. The lesions with the highest uptake in each patient are evaluated according to EORTC, PERCIST and RECIST classifications to discriminate between patients who respond (complete and partial response) from those who do not respond (stable and progressive disease) to treatment. Metabolic Tumor Volume (MTV) and Total Lesion Glycolysis (TLG) are also used to evaluate therapeutic response. MTV indicates the volume of metabolically active tumors; TLG is the product between SUV mean and MTV. In literature, there are no cut-off points for therapy evaluation based on TLG or MTV variations (Δ) in sequential scans. In order to estimate cut-off values for these parameters, receiver operating characteristic (ROC) curves are used. RECIST classification is used as the outcome for the ROC analysis. Kaplan-Meier test is used to calculate Overall Survival (OS) time. OS is compared between responders and non-responders using a log-rank test. The level of statistical significance is defined as a p-value (p) of less than 0.05. Results: The ROC analysis indicates a cut-off point of -36% for ΔTLG, and -8% for ΔMTV. The Kaplan-Meier analysis shows that RECIST, ∆TLG, and ∆MTV prove to be a significant prognostic factor for predicting OS. For RECIST responder patients median OS is 595 days whereas for non-responder patients median OS is 238 days. ΔTLG shows a median OS of 492 days for responders and 238 days for non-responders. ΔMTV shows a median of 423 days for responders versus 188 days for non-responders. Conversely, EORTC and PERCIST classifications are inadequate to discriminate between responder and non-responder patients (p>0.13). For this reason, we use ROC analysis to propose an alternative PERCIST threshold of 17% for an early therapy monitoring. Conclusion: PET examinations provide an early identification of patients who benefit from platinum-based treatment. Results confirm that TLG proves a strong early prognostic factor in patients with NSCLC and could play a significant role in the field of personalized medicine, avoiding the unnecessary administration of non-curative and toxic drugs to preserve the patient’s quality of life.

47. Modelled microgravity does not modify the yield of chromosome aberrations induced by high-energy protons in human lymphocytes.

Author

Manti L, Durante M, Cirrone GA, Grossi G, Lattuada M, Pugliese M, Sabini MG, Scampoli P, Valastro L, and Gialanella G

Subjects
Cell Proliferation radiation effects, Cell Size radiation effects, Cell Survival radiation effects, Cells, Cultured, Dose-Response Relationship, Radiation, Humans, Lymphocytes cytology, Chromosome Aberrations radiation effects, Lymphocytes physiology, Lymphocytes radiation effects, Protons, Weightlessness Simulation methods
Abstract

The aim was to evaluate the effect of modelled microgravity on radiation-induced chromosome aberrations (CAs). G0 peripheral blood lymphocytes were exposed to 60 MeV protons or 250 kVp X-rays in the dose range 0-6 Gy, and allowed to repair DNA damage for 24 h under either normal gravity or microgravity modelled by the NASA-designed rotating-wall bioreactor. Cells were then stimulated to proliferate by phytohaemagglutinin (PHA) under normal gravity conditions and prematurely condensed chromosomes were harvested after 48 h. CAs were scored in chromosomes 1 and 2 by fluorescence in-situ hybridization. Proliferation gravisensitivity was examined by cell growth curves and by morphological evaluation of mitogen-induced activation. Cell replication rounds were monitored by bromodeoxyuridine labelling. Modelled microgravity markedly reduced PHA-mediated lymphocyte blastogenesis and cell growth. However, no significant differences between normal gravity and modelled microgravity were found in the dose-response curves for the induction of aberrant cells or total interchromosomal exchange frequency. Rotating-wall bioreactor-based microgravity reproduced space-related alterations of mitogen stimulation in human lymphocytes but did not affect the yield of CAs induced by low-linear energy transfer radiation.

Published
2005
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48. Preliminary results on a dedicated silicon diode detector for proton dosimetry.

Author

De Angelis C, Onori S, Pacili M, Cirrone GA, Cuttone G, Raffaele L, and Sabini MG

Subjects
Phantoms, Imaging, Radiometry instrumentation, Radiometry methods, Reproducibility of Results, Silicon, Protons
Abstract

The present work reports preliminary measurements on the behaviour of a new p-type stereotactic silicon diode. Hi-pSi, produced by Scanditronix and dedicated to proton dosimetry. Diode response was investigated in low-energy proton beams (26.7 MeV and 12 MeV nominal energy), mainly with attention to stability, linearity, dose rate and energy dependence of the detector response. Three different Hi-pSi diodes of the same type were investigated. The diode response was linear with dose and the standard deviation of repeated readings was less than 2.5%. A marked dependence on dose rate was observed for one of the diodes (a response increase of 47% in the 0.7-11 Gy x min(-1) range). After the dose rate and water to silicon mass collision stopping power ratio correction of the diode response in the depth dose measurements, the difference, at the Bragg peak, with respect to the reference chamber was about 4%, ascribed to poor knowledge of the materials in front of the sensitive volume. The diode response was also nearly independent of linear energy transfer (LET) in the 9.6-21.5 MeV effective energy range.

Published
2002
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49. The use of thermoluminescent detectors for measurements of proton dose distribution.

Author

Sabini MG, Raffael L, Bucciolini M, Cirrone GA, Cuttone G, Lo Nigro S, Mazzocchi S, Salamone V, and Valastro LM

Subjects
Calibration, Reference Values, Reproducibility of Results, Protons, Thermoluminescent Dosimetry methods
Abstract

The aim of this work was to investigate the use of TLD-100 detectors in the field of relative dosimetry in proton eye facilities. These dosemeters, of different sizes, were used to measure transverse and longitudinal distributions of 62 MeV unmodulated proton beams at INFN-LNS in Catania. Comparison with other detectors, such as ionisation chambers, GAF and radiographic film, is extensively discussed.

Published
2002
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50. The late effects of proton irradiation on cell growth, cell cycle arrest and apoptosis in a human melanoma cell line.

Author

Ristic-Fira A, Nikolic D, Petrovic I, Ruzdijic S, Raffaele L, Sabini MG, Cirrone GA, Cuttone G, Farruggia G, Masotti L, and Kanazir DT

Subjects
Cell Survival radiation effects, Dose-Response Relationship, Radiation, G1 Phase radiation effects, G2 Phase radiation effects, Genes, p53 radiation effects, Humans, Melanoma, Mitosis radiation effects, Resting Phase, Cell Cycle radiation effects, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, Tumor Suppressor Protein p53 radiation effects, Apoptosis radiation effects, Cell Cycle radiation effects, Cell Division radiation effects, Protons
Abstract

The aim of this work is the in vitro study of the late effects of single proton irradiation on HTB63 human melanoma cell growth, cell cycle and cell death. The experimental conditions were focused on analyzing the effects of irradiation on the periphery of tumour that can be, in clinical practice, close to critical organs. Confluent cell monolayers were irradiated with single doses ranging from 1 - 20 Gy, using proton beams having an energy of 22.6 MeV at the target. Antiproliferative effect of protons, cell cycle analysis and initiation of cell death, were followed 48 hours after irradiation. The inhibition of melanoma cell growth was observed, especially after single application of 12 and 16 Gy. Cell cycle analysis and cell viability have shown the G2/M and G1/G0 arrest of irradiated cells correlating with the increase of the applied dose. The flow cytometric analysis has shown presence of apoptotic nuclei. These data demonstrate that irradiation with protons, under the chosen experimental conditions, have significant effects on melanoma cell growth inhibition being dose dependent, G2/M cell cycle arrest and appearance of apoptotic nuclei, even 48 hours after irradiation. The results obtained may help the understanding of the relationship between cell proliferation, death and cell cycle regulation of melanomas after proton irradiation.

Published
2001

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