Stefano Tomatis

Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Milano, Lombardy, Italy

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Publications (71)126.14 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Aim: To analyze the patterns of locoregional failure following intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) at our institution, as part of an internal quality assurance program. We aimed to investigate the potential existence of a correlation between any part of the IMRT process and clinical outcome. Methods & materials: A total of 106 non-metastatic NPC patients consecutively treated with IMRT (with or without chemotherapy) were analyzed. Radiotherapy was administered using a sequential or simultaneous integrated boost approach at the total prescribed dose of 66-70 Gy (2.00-2.12 Gy per fraction). MRI studies of recurrences were recorded with the planning computed tomography studies to identify volume of failure. Recurrence-related characteristics were analyzed with respect to the original treatment. Failures were classified as 'in-field', 'marginal' or 'out-field' if at least 95, 20-95 or less than 20% of the volume of failure, respectively, was within 95% of the total prescription dose. Results: With a median follow-up of 43.4 months, 5-years local control, regional control, locoregional control and overall survival rates were 87.7, 88.0, 83.5 and 81.3% respectively. A total of 21 failures were registered in 15 patients. In particular, ten failures (47.6%) were classified as 'in-field' (seven local failures and three regional failures [RFs]), nine failures (42.9%) as 'marginal' (five local failures and four RFs) and only two failures (9.5%) as 'out-field' (both RFs). The most relevant causes of failures were suboptimal target definition and target coverage as well as a longer than planned overall treatment time. Conclusion: IMRT determines excellent outcome in NPC patients. However, great attention in all IMRT steps is necessary to reduce potential causes of failure.
    Future Oncology 01/2013; 9(1):103-14. · 3.20 Impact Factor
  • European Urology Supplements 11/2012; 11(5):220. · 3.37 Impact Factor
  • European Urology Supplements 11/2012; 11(5):187–188. · 3.37 Impact Factor
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    ABSTRACT: The aim of this study was to develop a model exploiting artificial neural networks (ANNs) to correlate dosimetric and clinical variables with late rectal bleeding in prostate cancer patients undergoing radical radiotherapy and to compare the ANN results with those of a standard logistic regression (LR) analysis. 718 men included in the AIROPROS 0102 trial were analyzed. This multicenter protocol was characterized by the prospective evaluation of rectal toxicity, with a minimum follow-up of 36 months. Radiotherapy doses were between 70 and 80 Gy. Information was recorded for comorbidity, previous abdominal surgery, use of drugs and hormonal therapy. For each patient, a rectal dose-volume histogram (DVH) of the whole treatment was recorded and the equivalent uniform dose (EUD) evaluated as an effective descriptor of the whole DVH. Late rectal bleeding of grade ≥ 2 was considered to define positive events in this study (52 of 718 patients). The overall population was split into training and verification sets, both of which were involved in model instruction, and a test set, used to evaluate the predictive power of the model with independent data. Fourfold cross-validation was also used to provide realistic results for the full dataset. The LR was performed on the same data. Five variables were selected to predict late rectal bleeding: EUD, abdominal surgery, presence of hemorrhoids, use of anticoagulants and androgen deprivation. Following a receiver operating characteristic analysis of the independent test set, the areas under the curves (AUCs) were 0.704 and 0.655 for ANN and LR, respectively. When evaluated with cross-validation, the AUC was 0.714 for ANN and 0.636 for LR, which differed at a significance level of p = 0.03. When a practical discrimination threshold was selected, ANN could classify data with sensitivity and specificity both equal to 68.0%, whereas these values were 61.5% for LR. These data provide reasonable evidence that results obtained with ANNs are superior to those achieved with LR when predicting late radiotherapy-related rectal bleeding. The future introduction of patient-related personal characteristics, such as gene expression profiles, might improve the predictive power of statistical classifiers. More refined morphological aspects of the dose distribution, such as dose surface mapping, might also enhance the overall performance of ANN-based predictive models.
    Physics in Medicine and Biology 03/2012; 57(5):1399-412. · 2.70 Impact Factor
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    ABSTRACT: Radiation doses delivered to the patient during high dose rate brachytherapy treatments are susceptible to many inaccuracies and may not accurately match the planned doses. Novel Fricke gel dosimetric catheters (FGDC) were developed in the laboratory to be used for in vivo measurements of high dose rate brachytherapy treatments and represent possible tools to increase treatment accuracy. In this study, the dosimetric compound adopted to achieve FGDC was studied in terms of dose sensitivity and linearity, and some potentialities and limits of its application were investigated. Results show that at doses higher than 400cGy, the dosimeter response is linear with the delivered dose until a saturation effect is observed at doses higher than 2800cGy. However, saturation is reached at lower doses as well with dose rates higher than 400cGy/min.
    Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment 01/2011; 652(1):888-890. · 1.14 Impact Factor
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    ABSTRACT: The purpose of the study was to develop a general method able to quantify the mutual disposition in the 3D space of critical organs with respect to the target when these structures are designed for a radiotherapy treatment plan. To that end, we introduce the "expansion intersection histogram", a function defined as the intersection between an organ at risk and the target volume, while the target is expanded in 3D. A software was developed to calculate the expansion intersection histogram of anatomical structures exported in a DICOM format from a commercial treatment planning system. A virtual phantom with spherical and cylindrical objects arranged in different dispositions in the 3D space was created for testing the software under known conditions. Expansion intersection histogram computation was tested against reference data derived analytically for spherical volumes, with a resulting maximum error of 0.5%. Specific geometric features derived from the expansion intersection histogram, such as the distance between a selected target and each different ideal volume included in the virtual phantom, well matched the corresponding theoretical expected values. The expansion intersection histogram was evaluated also for the anatomical structures of a real patient. Data show this method as a tool to effectively take into account the mutual disposition of each critical organ with respect to the target, summarized in characteristics of distance, shape and orientation. The expansion intersection histogram method integrates and extends other preexisting modalities for evaluating the geometrical relationships among radiotherapy volumes and could be used to improve planning optimization.
    Tumori. 01/2011; 97(4):503-9.
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    ABSTRACT: Fricke-gel layer dosimeters (FGLDs) have shown promising features for attaining absolute measurements of the spatial distribution of the absorbed dose in radiotherapy. Good precision of results (within 3%) is achieved by means of calibration of each single dosimeter before measurement. The calibration is performed irradiating the dosimeter at a uniform and precisely known dose, in order to get a calibration matrix that must be used, with pixel-to-pixel manipulation, to obtain the dose image. A study of the trend in time of dosimeter response after one or more exposures was carried out and calibration protocols were suitably established and verified.
    01/2011;
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    ABSTRACT: Because of its high thickness, nodular melanoma often bears a poor prognosis. Thus, an earlier diagnosis of this type of lesion while it is still thin would be an important step in secondary prevention. The principal aim of the present study was to better define the initial clinical features of nodular melanoma to allow an early diagnosis. A secondary aim was to establish the prognosis of this type of lesion. We retrospectively studied and illustrated the clinical features of 11 small (< or = 6 mm maximum diameter) cutaneous nodular melanomas seen and treated during a 10-year period. Prognostic characteristics of the various lesions were also described. The results of the study help to describe a small nodular melanoma as a dark and/or pink/red raised lesion, which may be evenly or unevenly colored, with well-defined borders, that often appears de novo. A correct clinical diagnosis was made in 7 of the cases. During a median follow-up of 6 years, none of the patients had local or distant relapses. Detection of small nodular melanoma is feasible by accurate visual inspection, provided that physicians are aware of this type of lesion and maintain the index of suspicion at a high level to bring about curative surgery.
    Tumori 01/2011; 97(1):35-8. · 0.92 Impact Factor
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    ABSTRACT: Radiotherapeutic treatment of cancer is best conducted if the prescription dose is given to the tumor while surrounding normal tissues are maximally spared. With the aim to meet these requirements the complexity of radiotherapy techniques have steadily increased under a strong technological impulse, especially in the last decades. One problem involves the rate of the particular disposition of the structures of interest in a patient. Recently the authors (Tomatis et al., 2010; 2011) have proposed a computational approach in order to represent quantitatively the geometrical features of organs at risk, summarized in characteristics of distance, shape and orientation of such organs in respect to the target. A basic problem to solve before to compute the risk index, is the segmentation of the organs involved in the radiotherapy planning. Here we described a 3D segmentation method by using the clinical computed tomography (CT) data of the patients. Our algorithm is based on different steps, a preprocessing phase where a nonlinear diffusion filter is applied; a level set based method for extract 2D countours; a postprocessing reconstruction of 3D volume from 2D segmented slices. Some comparisons with manually traced segmentation by clinical experts are provided.
    Image Analysis & Stereology. 01/2011; 30(3).
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    ABSTRACT: Fricke-gel layer dosimeters (FGLD) and Fricke gel dosimetric catheters (FGDC) have been designed and tested with the aim of enquiring their suitability for HDR 192Ir brachytherapy source control and for in-vivo dose verification during treatment. Anisotropy function measurements have been carried out with FGLDs in which a thin plastic tube has been placed in for the 192Ir source insertion. FGDCs are constituted by plastic tubes (3 mm of external diameter and 13 cm of length) filled with the dosimeter-gel. Absorbed dose images and profiles were attained by means of optical analysis. Dedicated software has been developed both for achieving anisotropy function values and for obtaining reliable results in visible light absorbance measurements across the thin cylindrical dosimeters. Preparation and analysis procedures have been optimised. The results confirm that the proposed methods are very promising for HDR brachytherapy dosimetry.
    Journal of Physics Conference Series 12/2010; 250(1):012089.
  • ASTRO 2010 (American Society for Radiation Oncology) annual meeting; 11/2010
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    ABSTRACT: The anisotropy function F(r,theta) has been recommended to account for the dose distribution anisotropy that results adopting sealed brachytherapy sources. This function is implemented in the American Association of Physicists in Medicine (AAPM) dose calculation formalism and is widely adopted by the currently available treatment planning systems. In this work, a method based on a suitably developed Fricke gel dosimeter with a built-in catheter and on an optical imaging system was developed for the characterization of F(r,theta) for an Ir-l92 source. At radial distances of 15, 20, 25 and 30 mm percentage differences between tabulated and measured data resulted to be almost always smaller than 3%. Fricke gel dosimeters result to be accurate tools for the Ir-l92 anisotropy function measurement. These instruments could be easily adopted in quality assurance protocolls to verify the anisotropy function of each newly installed Ir-l92 source.
    04/2010;
  • Fuel and Energy Abstracts 01/2010; 78(3).
  • Fuel and Energy Abstracts 01/2010; 78(3).
  • Fuel and Energy Abstracts 01/2010; 78(3).
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    ABSTRACT: To report the outcome of a consecutive series of patients with nonmetastatic nasopharyngeal carcinoma (NPC), focusing on the impact of treatment-related factors. Between 2000 and 2006, 87 patients with NPC were treated with either conventional (two- or three-dimensional) radiotherapy (RT) or with intensity-modulated RT (IMRT). Of these patients, 81 (93%) received either concomitant CHT (24%) or both induction and concomitant chemotherapy (CHT) (69%). Stage was III in 36% and IV in 39% of patients. Outcomes in this study population were compared with those in the previous series of 171 patients treated during 1990 to 1999. With a median follow-up of 46 months, actuarial rates at 3 years were the following: local control, 96%; local-regional control, 93%; distant control (DC), 90%; disease-free survival (DFS), 82%; overall survival, 90%. In Stage III to IV patients, distant control at 3 years was 56% in patients treated with concomitant CHT only and 92% in patients treated with both induction and concomitant CHT (p = 0.014). At multivariate analysis, histology, N-stage, RT technique, and total RT dose had the strongest independent impact on DFS (p < 0.05). Induction CHT had a borderline effect on DC (p = 0.07). Most dosimetric statistics were improved in the group of patients treated with IMRT compared with conventional 3D technique. All outcome endpoints were substantially better in the study population compared with those in the previous series. Outcome of NPC has further improved in the study period compared with the previous decade, with a significant effect of RT technique optimization. The impact of induction CHT remains to be demonstrated in controlled trials.
    International journal of radiation oncology, biology, physics 02/2009; 74(3):774-80. · 4.59 Impact Factor
  • Gut 03/2008; 57(2):279, author reply 279-80. · 10.73 Impact Factor
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    ABSTRACT: To quantify the incidence and severity of acute local toxicity in head and neck cancer patients treated with radiotherapy (RT), with or without chemotherapy (CHT), using the Common Terminology Criteria for Adverse Events, version 3.0 (CTCAE v3.0), scoring system. Between 2004 and 2006, 149 patients with head and neck cancer treated with RT at our center were prospectively evaluated for local toxicity during treatment. On a weekly basis, patients were monitored and eight toxicity items were recorded according to the CTCAE v3.0 scoring system. Of the 149 patients, 48 (32%) were treated with RT alone (conventional fractionation), 82 (55%) with concomitant CHT and conventional fractionation RT, and 20 (13%) with accelerated-fractionation RT and CHT. Severe (Grade 3-4) adverse events were recorded in 28% (mucositis), 33% (dysphagia), 40% (pain), and 12% (skin) of patients. Multivariate analysis showed CHT to be the most relevant factor independently predicting for worse toxicity (mucositis, dysphagia, weight loss, salivary changes). In contrast, previous surgery, RT acceleration and older age, female gender, and younger age, respectively, predicted for a worse outcome of mucositis, weight loss, pain, and dermatitis. The T-score method confirmed that conventional RT alone is in the "low-burden" class (T-score = 0.6) and suggests that concurrent CHT and conventional fractionation RT is in the "high-burden" class (T-score = 1.15). Combined CHT and accelerated-fractionation RT had the highest T-score at 1.9. The CTCAE v3.0 proved to be a reliable tool to quantify acute toxicity in head and neck cancer patients treated with various treatment intensities. The effect of CHT and RT acceleration on the acute toxicity burden was clinically relevant.
    International Journal of Radiation OncologyBiologyPhysics 03/2008; 70(2):330-7. · 4.52 Impact Factor
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    ABSTRACT: Various instruments based on acquisition and elaboration of images of pigmented skin lesions have been developed in an attempt to in vivo establish whether a lesion is a melanoma or not. Although encouraging, the response of these instruments, e.g. epiluminescence microscopy, reflectance spectrophotometry and fluorescence imaging, cannot currently replace the well-established diagnostic procedures. However, in place of the approach to instrumentally assess the diagnosis of the lesion, recent studies suggest that instruments should rather reproduce the assessment by an expert clinician of whether a lesion has to be excised or not. The aim of this study was to evaluate the performance of a spectrophotometric system to mimic such a decision. The study involved 1794 consecutively recruited patients with 1966 doubtful cutaneous pigmented lesions excised for histopathological diagnosis and 348 patients with 1940 non-excised lesions because clinically reassuring. Images of all these lesions were acquired in vivo with a multispectral imaging system. The data set was randomly divided into a train (802 reassuring and 1003 excision-needing lesions, including 139 melanomas), a verify (464 reassuring and 439 excision-needing lesions, including 72 melanomas) and a test set (674 reassuring and 524 excision-needing lesions, including 76 melanomas). An artificial neural network (ANN(1)) was set up to perform the classification of the lesions as excision-needing or reassuring, according to the expert clinicians' decision on how to manage each examined lesion. In the independent test set, the system was able to emulate the clinicians with a sensitivity of 88% and a specificity of 80%. Of the 462 correctly classified as excision-needing lesions, 72 (95%) were melanomas. No major variations in receiver operating characteristic curves were found between the test and the train/verify sets. On the same data set, a further artificial neural network (ANN(2)) was then architected to perform classification of the lesions as melanoma or non-melanoma, according to the histological diagnosis. Having set the sensitivity in recognizing melanoma to 95%, ANN(1) resulted to be significantly better in the classification of reassuring lesions than ANN(2). This study suggests that multispectral image analysis and artificial neural networks could be used to support primary care physicians or general practitioners in identifying pigmented skin lesions that require further investigations.
    Physics in Medicine and Biology 06/2007; 52(9):2599-613. · 2.70 Impact Factor
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    ABSTRACT: The complex inner layered structure of skin influences the photon diffusion inside the cutaneous tissues and determines the reflectance spectra formation. Phantoms are very useful tools to understand the biophysical meaning of parameters involved in light propagation through the skin. To simulate the skin reflectance spectrum, we realized a multilayered skin-like phantom and a multilayered skin phantom with a melanoma-like phantom embedded inside. Materials used were Al(2)O(3) particles, melanin of sepia officinalis and a calibrator for haematology systems dispersed in transparent silicon. Components were optically characterized with indirect techniques. Reflectance phantom spectra were compared with average values of in vivo spectra acquired on a sample of 573 voluntary subjects and 132 pigmented lesions. The phantoms' reflectance spectra agreed with those measured in vivo, mimicking the optical behaviour of the human skin. Further, the phantoms were optically stable and easily manageable, and represented a valid resource in spectra formation comprehension, in diagnostic laser applications and simulation model implementation, such as the Monte Carlo code for non-homogeneous media.
    Physics in Medicine and Biology 06/2007; 52(10):N229-39. · 2.70 Impact Factor

Publication Stats

585 Citations
126.14 Total Impact Points

Institutions

  • 2006–2012
    • Fondazione IRCCS Istituto Nazionale dei Tumori di Milano
      • Prostate Cancer Program
      Milano, Lombardy, Italy
  • 2007
    • Istituto Nazionale Tumori "Fondazione Pascale"
      Napoli, Campania, Italy
  • 2005–2007
    • University of Milan
      • Department of Physics
      Milano, Lombardy, Italy
  • 1996–2007
    • Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori
      Meldola, Emilia-Romagna, Italy
  • 1995
    • National Cancer Institute
      Μπογκοτά, Bogota D.C., Colombia