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R Orecchia

Publications and source records attributed to R Orecchia.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Opto-electronic techniques and 3D body surface reconstruction for the control of patient positioning in the radiotherapy of breast cancer].

PURPOSE: In radiotherapy clinical practice, the currently existing gap between the high degree of accuracy in treatment planning and, the possibility of conforming the high-energy radiation beams on the one hand, and the uncertain set-up of each irradiation session on the other is a decisive factor for optimizing radiation treatment. Indeed there is wide experimental evidence that the current methods used for patient alignment and immobilization do not guarantee the necessary precision in delivering therapy with respect to the specifications of the treatment plan. The main reason for this is the lack of control systems that may be applied systematically to provide quantitative real-time feedback on the quality of patient repositioning and immobility during radiation emission. MATERIAL AND METHODS: Opto-electronic techniques and body surface registration methods were sygergisically used for the automatic three-dimensional verification and correction of patient position at the therapy unit. The method is based on radiotherapy applications of real-time opto-electronic human motion analysis using passive markers to control patient repositioning and to acquire and describe body surfaces in three dimensions. The quantitative detection of the localization error relies on the real-time detection of the position of an hybrid set of control points, namely physical passive markers and laser light markers, and their immediate comparison with a reference data set. The data set consists of the reference positions of the passive markers and a three-dimensional model of the body surface. The method was experimentally tested at the Radiotherapy Division of the European Institute of Oncology to control the repositioning of a phantom and of a volunteer, with reference to the clinical realignment procedure applied for breast cancer radiotherapy. RESULTS: The results confirm that the technique represents a valuable method to detect and automatically correct localization errors in the irradiation set-up. The use of the information provided by the laser markers allows one to reduce the potential inaccuracies in the manual relocation of the passive markers on the subject's skin and guarantees that position control is based on a redundant set of data describing the three-dimensional localization and configuration of the irradiated body surface portion. The experimental results show that the initial displacements of the controlled body area were systematically reduced to median values below 1 millimeter and 1.2 millimeters for the phantom and the volunteer, respectively. CONCLUSIONS: The synergistic use of opto-electronic technologies and stereophotogrammetric techniques associated to surface registration methods proved to provide an accurate description of the spatial transformation between the reference position and the actual position of the controlled body area. This allowed us to define an effective procedure to correct the patients position and recover the quality of the irradiation set-up, in agreement with the clinical requirements. The reported results confirm that the dynamic sensing of the body surface by opto-electronic technologies is a particularly promising technique that allows to systematically achieve swift and accurate patient alignment, thus ensuring that the treatment plan specifications are reproduced in the reality of each irradiation session.

Algorithms↗
PubMed2000

Ki-ras activation in vitro affects G1 and G2M cell-cycle transit times and apoptosis.

Mutant ras genes occur frequently in human neoplasia and, in particular, in pancreatic, colorectal, and lung adenocarcinomas. Recent evidence suggests that G-->T and G-->C transversions of the Ki-ras gene in codon 12 may lead to biological effects in vitro and in vivo that may be associated with an abnormal cell cycle and increased tumour aggressiveness. The role of Ki-ras activation (a G-->C transversion in codon 12, arginine for glycine) in the cell cycle and apoptosis was investigated using control and permanently transfected NIH3T3 mouse fibroblasts. Flow cytometry was used to evaluate the G1-, S- and G2M-phase transit times, the potential doubling time, the growth fraction, and the cell loss factor during asynchronous exponential growth. Apoptosis was induced in both cell lines by absence of growth factors for an extended period of time (72 h) and quantitatively evaluated using the TUNEL method coupled with flow cytometry. It was found that codon 12 G-->C Ki-ras transfected cells compared with controls, had a significant prolongation of G1 by about 50%, a reduction of the G2M transit time by 30%, and a decrease of the cell loss factor by about 90%. Apoptotic cells were about 10% in control and less than 0.5% in Ki-ras transfected cells after 72 h starvation-confluency. These data suggest that codon 12 G-->C Ki-ras activation in mouse NIH3T3 fibroblasts is associated with deregulation of checkpoint controls in the G1 and G2M phases of the cell cycle and inhibition of apoptosis. It appears plausible that these cell mechanisms are related to a proliferative advantage and that they may also be important in the progression of human tumours characterized by specific Ki-ras mutations.

3T3 Cells↗
PubMed2000

Real-time opto-electronic verification of patient position in breast cancer radiotherapy.

OBJECTIVE: The clinical application of an opto-electronic system for real-time three-dimensional (3D) control of patient position in breast cancer radiotherapy is described. The specific features of the motion analysis technology (shape recognition of passive markers) are detailed, and the outcomes of its clinical use for quantitative position control and immobility verification of the thoracic irradiation field during breast cancer treatment are reported. MATERIALS AND METHODS: The position control system is based on the ELITEtrade mark opto-electronic motion analyzer, which provides in real time the 3D coordinates of a set of passive markers (plastic hemispheres 3 mm in diameter) previously placed on selected landmarks on the patient's skin. The system-dedicated hardware performs marker recognition by means of 2D correlation of shape with a predefined marker modeling mask. This feature ensures a high accuracy, even with small marker dimensions, and successful analysis in a noisy environment (due to room light, reflexes, etc.). The patient repositioning control was based on a comparison between the current positions of the markers and a corresponding reference configuration. The resulting marker displacements were graphically displayed in real time for immediate control. This information was not provided to the operator as a repositioning tool. Instead, the kinematic data was stored for subsequent off-line analysis aimed at quantifying the different factors contributing to patient mis-positioning (initial repositioning errors, patient's breathing, and random movements) when conventional means for patient alignment (laser centering) and immobilization (casting techniques) are used. RESULTS: Clinical application of the system revealed median 3D localization errors for the directly controlled anatomical landmarks of around 4.5 mm. This value is proposed to represent the intrinsic accuracy of conventional laser-centering techniques in breast cancer radiotherapy, including the effects of patient body deformations. When the positional inaccuracies introduced by patients' respiration were also considered, the extent of the resulting 3D mis-positioning of the control points increased to median values of up to 8 mm. CONCLUSIONS: The reported clinical trial confirms the significant role that real-time opto-electronic motion analysis based on passive markers can have in augmenting the accuracy of patient repositioning and immobility verification in the radiotherapy of a non-rigid body area while also accounting for physiological movements. Evaluation of the data collected during each irradiation session for five patients provided valuable information concerning the optimization of the efficacy of traditional methods for patient centering and immobilization.

Breast Neoplasms↗
PubMed2000

Real-time three-dimensional motion analysis for patient positioning verification.

BACKGROUND AND PURPOSE: This paper describes the technology and methods involved in a system for automatically checking the position of patients at radiotherapy units. This is proposed for improving the accuracy in the irradiation geometrical set-up, which is a crucial factor in radiotherapy quality control. MATERIALS AND METHODS: The system is based on real-time opto-electronics and close-range photogrammetry and detects multiple passive markers placed on selected patient skin landmarks. Patient alignment and position monitoring is carried out by comparing the current three-dimensional positions of the markers with those of an initial reference position acquired during the simulation procedure and/or the first irradiation session. The system was used to measure the accuracy of conventional laser centering techniques for patient repositioning. Inaccuracies due to breathing and random movements were also taken into account. Professional technicians were asked to reposition three volunteer subjects carefully using a traditional laser centering procedure. RESULTS: The results revealed significant repositioning errors even in highly controlled conditions, affecting particularly body areas relatively far from the skin reference points used for laser alignment. CONCLUSIONS: The outcome of the experimental application of this technology confirms its potential as a tool for patient repositioning and automatic detection of any errors caused by breathing or other unpredictable movements. The real-time feedback on the patient's position given by the system provides operators with appropriate visual indices and allows them to take suitable countermeasures in case of significant failures. In addition, the use of the system output for automatic position control is envisaged.

Artifacts↗
PubMed2000

Analysis of erythrocyte glycophorin-A variants by flow cytometry in lung disease patients detects the effect of tobacco smoke.

The glycophoryn A (GPA) assay evaluates somatic in vivo mutations. It is considered a cumulative biodosimeter for genotoxic exposures and is under evaluation in cancer risk assessment. GPA, a polymorphic membrane protein of the erythrocytes, determines the MN blood groups. The NO and NN variant frequencies (VF) may be detected in MN subjects (about 50% of the population) by flow cytometry using two differently labelled antibodies. We explored if GPA NO and NN VF might be relevant to the assessment of individual lung cancer risk and susceptibility, in a small population with a high prevalence of heavy tobacco smokers: 8 lung cancer patients and 16 subjects with non-malignant lung diseases associated with increased risk of lung cancer. There was a wide interindividual variability and complete overlap between non-neoplastic and neoplastic patients. A significant positive correlation was seen with smoking duration in NO VF (p = 0.04, age-adjusted). Current smokers (n = 12) displayed higher NO values than never (n = 1) or ex-smokers (n = 11), 36.3 +/- 18.2 and 21.0 +/- 13.2, respectively (p < 0.01). No association was shown with occupational exposure. The present exploratory study suggests that assessment of individual lung cancer risk and susceptibility by the GPA assay does not seem to be feasible. The assay appears to provide a biomarker of longterm exposure to tobacco smoke.

Aged↗
PubMed1999

Intratumor heterogeneity of chromosome 1, 7, 17, and 18 aneusomies obtained by FISH and association with flow cytometric DNA index in human colorectal adenocarcinomas.

BACKGROUND: The origin and evolution of somatic chromosome aberrations in colorectal cancer is still poorly understood. The data in the literature suggest that some specific chromosome aberrations are more common. It is not known, however, if there is a correlation of these with near-diploid and high aneuploidy previously proposed to be a characteristic of the adenoma-carcinoma sequence. METHODS: Chromosome 1, 7, 17 and 18 numerical aberrations and 1p deletions were evaluated by fluorescence in situ hybridization analysis for 20 human sporadic colorectal adenocarcinomas in 70 distinct tumor sectors and correlated with flow cytometric DNA index (DI) values. RESULTS: Aneusomy for at least one of the investigated chromosomes was observed in 60 of 70 tumor sectors corresponding to 19 of 20 adenocarcinomas (95%). Deletions at 1p, observed in 8 of 18 adenocarcinomas (44%), were intratumor homogeneous in 7 of 8 tumors. In contrast, the other aberrations were intratumor heterogeneous. Aneusomies of chromosomes 1, 7, and 17 were strongly associated with DNA high aneuploidy (DI > or = 1.4), whereas aneusomy of chromosome 18 and 1p deletions were equally common among DNA diploid and near-diploid tumors (DI < 1.4 and DI not equal to 1). CONCLUSIONS: Overall, these data suggest the existence of different aneuploidization routes correlated with specific chromosome aberrations. In addition, intratumor homogeneity of 1p deletions appears to be an indication of early occurrence or strong selection. We also suggest that tumors with monosomies and in particular monosomies-trisomies for the same chromosomes support a model of aneuploidization and chromosome instability during the colorectal tumor progression based on loss of symmetry during chromosome segregation (Giaretti: Lab Invest 71:904-910, 1994).

Adenocarcinoma↗
PubMed1999

Treatment of malignant neoplasms of the parotid gland.

In this study we evaluated the effects of surgical and radiotherapy treatment on local control in 126 patients with malignant tumors of the parotid gland. The most frequently observed malignant tumors were high-grade tumors (68%). Surgical treatment was performed in 81 patients (83.5%). Total conservative parotidectomy was the most frequent procedure (74%), and radiotherapy was performed in 81 patients (83.5%). The global survival rate was approximately 54% at 5 years, whereas disease-free survival was 47% at 5 years. No statistically significant difference in survival rate was found between conservative (52% at 5 years) and radical treatment of the seventh cranial nerve (43% at 5 years). The incidence of recurrent cancer was 25.7% (25 of 97), of which 88% developed during the first 2 years. We report some of the clinical and histologic factors that can influence the prognosis of the disease.

Adolescent↗
PubMed1999

Prediction of response to primary chemotherapy for operable breast cancer.

The use of primary systemic cytotoxics leads to a high remission rate in patients with breast cancer. Response was identified as an important variable associated with survival. Thus, features which predict response, are potentially relevant for planning treatments and improving survival. Retrospectively, we investigated several histopathological features (expression of oestrogen and progesterone receptors, Mib1, bcl-2, c-erbB-2, and p53) prior to two programmes of either sequential preoperative chemotherapy (doxorubicin plus cyclophosphamide) and radiotherapy (Group A), or preoperative chemotherapy (5-fluorouracil, folinic acid and vinorelbine) alone (Group B) in patients with operable breast cancer. After three courses, patients with a partial or complete response were given a further three courses, which was followed for patients in Group A by radiotherapy 50 Gy plus a boost of 10 Gy. All patients were submitted to surgery after completion of preoperative treatment and pathology material from 73 patients (median age, 49 years, range, 30-70; performance status, 0-1; 68 T2, 5 T3) was obtained. The overall response rate according to radiological and clinical evaluation was 59% (68% for Group A and 49% for Group B). 12 of 14 patients with p53-positive tumours and 31 of 59 with p53-negative tumours responded (P = 0.04). 6 of 7 patients with elevated c-erbB-2 had a response compared with 37 of 66 patients in the group with c-erbB-2 negative tumours (P = 0.03). Mib1 expression decreased substantially (> or = 50%) in 25 patients during treatment, of whom 20 responded compared with 21 of 48 patients with a lower decrease (P = 0.04). Response was observed in 28 of 37 patients with high baseline Mib1 (> 20%) and in 15 of 36 patients in the low Mib1 group (P = 0.05). Finally, 32 of 44 tumours with low expression of progesterone receptors responded compared with 11 of 29 tumours with high receptors expression (P = 0.05). These markers might be useful for tailoring primary and postsurgical systemic treatments.

Adult↗
PubMed1999

Surfing prognostic factors in head and neck cancer at the millennium.

The ability to reliably predict cancer outcome could tailor therapy to the aggressiveness of the tumour to achieve the best results in terms of loco-regional control, overall survival and quality of life. Retrospective and prospective clinical trials involving large series of patients have validated some predictive clinical and pathological factors, whereas the utility of many other prognostic factors has not been established. This has led to some confusion in clinical practice. In order to clarify the significance, role and cost of these prognostic factors we carried out a Medline search of all papers published between 1993 and 1998 concerning the reliability and cost of markers with prognostic significance, in head and neck squamous cell carcinoma, and assessed the results according to a number of criteria relating to reliability and cost. Regarding reliability we classified prognostic factors into: (1) those with a proven significance based on the fact that they were unanimously reported as having an independent statistical correlation with outcome and prognosis; and (2) those for which results were not unanimous, and which significance is still controversial. Cost analysis showed a substantial difference between validated tests which are of low cost and experimental tests which are expensive. Based on these data regarding both the reliability and cost of each prognostic factor, we propose guidelines for their use in clinical practice in the year 2000.

Biomarkers, Tumor↗
PubMed1999

K-ras2 activation and genome instability increase proliferation and size of FAP adenomas.

The possible role of K-ras2 mutations and aneuploidy toward increase of proliferation and adenoma size in Familial Adenomatous Polyposis (FAP) adenomas is not known. The present study addresses these issues by investigating 147 colorectal adenomas obtained from four FAP patients. The majority of adenomas had size lower than or equal to 10 mm (86%), low grade dysplasia (63%), and were preferentially located in the right colon (60%). Normal mucosa samples were obtained from 19 healthy donors. Three synchronous adenocarcinomas were also investigated. K-ras2 mutation spectrum was analysed by PCR and Sequence Specific Oligonucleotide (SSO) hybridization, while flow cytometry (FCM) was used for evaluating degree of DNA ploidy and S-phase fraction. Overall, incidences of K-ras2 mutations, DNA aneuploidy and high S-phase values (>7.2%) were 6.6%, 5.4% and 10.5%, respectively. In particular, among the adenomas with size lower than 5 mm, K-ras2 mutation and DNA aneuploidy frequencies were only slightly above 1%. Statistically significant correlations were found between K-ras2 and size, DNA ploidy and size and K-ras2 and S-phase (p < 0.001). In particular, among the wild type K-ras2 adenomas, high S-phase values were detected in 8% of the cases versus 57% among the K-ras2 mutated adenomas (p = 0.0005). The present series of FAP adenomas indicates that K-ras2 activation and gross genomic changes play a role toward a proliferative gain and tumour growth in size.

Adenocarcinoma↗
PubMed1999

Small cell carcinoma of the esophagus.

Small cell carcinoma of the esophagus (SCEC) is a rare tumor with its particular biologic features, distinct from squamous and glandular carcinoma of esophagus. Although initial symptoms can be similar (with metastatic dissemination and paraneoplastic syndromes at presentation more frequent in SCEC), differences in age and sex distribution, tumor location, radiological and endoscopic findings, clinical course and prognosis have been observed between SCEC and other esophageal malignancies. SCEC should be considered a systemic disease, and by analogy to bronchogenic small cell carcinoma, multimodality approach including chemotherapy is recommended. In patients with limited disease, irradiation or surgery should be offered after induction chemotherapy to manage local disease. However, optimal treatment schedule has not yet been defined. In the future, registration of all SCEC cases and careful analysis of prognostic factors in the larger multi-institutional series could contribute to further progress in treatment outcome.

Carcinoma, Small Cell↗
PubMed1998

Induction chemotherapy followed by simultaneous hyperfractionated radiochemotherapy in advanced head and neck cancer. A pilot study.

PURPOSE: To evaluate the feasibility of induction chemotherapy followed by concomitant chemotherapy and hyperfractionated irradiation in locally advanced, inoperable head and neck cancer. METHODS: A pilot study was undertaken comprising 3 cycles of cisplatinum (100 mg/m2, day 1) and 5-fluorouracil (1000 mg/m2 in continuous intravenous infusion over the first 120 h) followed by bifractionated radiotherapy applied to tumor/involved lymph nodes up to the dose of 74.4 Gy given in 2 fractions of 1.2 Gy daily for 5 days a week combined with concomitant weekly cisplatinum infusion (50 mg/m2). RESULTS: Six patients were enrolled in the study. All of them completed the protocol therapy. Severe mucositis and myelotoxicity were the most common acute side effects observed in all and in 5 of the patients, respectively. Acute toxicity required interruption of concomitant chemotherapy in 5 cases and in 2 interruption of radiotherapy was necessary. Opioid analgesic parenteral therapy was administered in 4 patients. Three of them had to be hospitalized. One patient experienced cerebral stroke 1 day after the completion of therapy and died 7 days later. Due to high acute toxicity, patient accrual was terminated after 6 patients. At the mean follow-up of 17 months, 4 patients are alive, 3 of them are free of disease and in 1 local progression has been diagnosed. CONCLUSIONS: High acute toxicity of induction cisplatinum and 5-fluorouracil followed by concomitant cisplatinum and hyperfractionated irradiation calls for less toxic treatment schedules in locally advanced inoperable head and neck cancer.

Adolescent↗
PubMed1998

Combined treatment of advanced oropharyngeal cancer with external radiotherapy and three-step radioimmunotherapy.

The prognosis of patients with locally advanced head and neck cancer remains grim due to poor locoregional tumour control. In the attempt to eradicate residual disease, various novel modalities have been tested, among which radioimmunotherapy (RIT) has shown some potential. We present a case of locally advanced oropharyngeal carcinoma successfully treated with a combination of various treatments including surgery, radio-chemotherapy and three-step RIT, with the avidin-biotin pretargeting system. A partial tumour response was achieved after surgery and radio-chemotherapy; persistent disease was documented at computed tomography (CT), ultrasound (US) and immunoscintigraphy (ISG) 10 weeks after the end of chemo-radiotherapy. The good correlation between the tracer localization in the scintigraphic images and residual mass visualized at CT suggested the application of three-step RIT using systemic administration of yttrium-90 (py) biotin. At present, 17 months after RIT, the patient is alive with no evidence of disease as documented by magnetic resonance imaging (MRI) and US. This is the first case of complete clinical remission of a head and neck carcinoma induced by combined treatment including pretargeted RIT with 90Y-biotin.

Aged↗
PubMed1998

Particle beam therapy (hadrontherapy): basis for interest and clinical experience.

The particle or hadron beams deployed in radiotherapy (protons, neutrons and helium, carbon, oxygen and neon ions) have physical and radiobiological characteristics which differ from those of conventional radiotherapy beams (photons) and which offer a number of theoretical advantages over conventional radiotherapy. After briefly describing the properties of hadron beams in comparison to photons, this review discusses the indications for hadrontherapy and analyses accumulated experience on the use of this modality to treat mainly neoplastic lesions, as published by the relatively few hadrontherapy centres operating around the world. The analysis indicates that for selected patients and tumours (particularly uveal melanomas and base of skull/spinal chordomas and chondrosarcomas), hadrontherapy produces greater disease-free survival. The advantages of hadrontherapy are most promisingly realised when used in conjunction with modern patient positioning, radiation delivery and focusing techniques (e.g. on-line imaging, three-dimensional conformal radiotherapy) developed to improve the efficacy of photon therapy. Although the construction and running costs of hadrontherapy units are considerably greater than those of conventional facilities, a comprehensive analysis that considers all the costs, particularly those resulting from the failure of less effective conventional radiotherapy, might indicate that hadrontherapy could be cost effective. In conclusion, the growing interest in this form of treatment seems to be fully justified by the results obtained to date, although more efficacy and dosing studies are required.

Central Nervous System Neoplasms↗
PubMed1998

Pre-operative chemotherapy and radiotherapy in breast cancer.

Primary systemic treatment of breast cancer with cytotoxics yields a high response rate and allows conservative surgical procedures in bulky tumours. In order to maximise local control of disease, two innovations were introduced in a pilot study. The first was to identify the good responders after three cycles of chemotherapy and to treat them with three additional cycles. The second was to also give this group of patients a full dose of radiotherapy before surgery with the aim of verifying the rate of pathological complete remissions in view of a possible treatment of breast primary with chemoradiotherapy only. Patients were treated with doxorubicin 60 mg/m2 and cyclophosphamide, 600 mg/m2 both intravenously on day 1, every 21 days for three courses. Partial or complete responders received three more courses followed by radiotherapy (50 Gy plus a 10 Gy boost). The others underwent immediate surgery. A total of 32 patients (median age, 50 years; range 28-69 years); performance status, 0-1; T2 22, T3 8, T4 2) were enrolled and were evaluable for response and side-effects. 9 patients had only three cycles of chemotherapy due to absence of response and 23 patients had six cycles of chemotherapy. Overall, 7 patients had a complete remission, 16 a partial remission and 9 had stable disease, for an overall response rate of 72% (95% confidence interval 53-86%). In the group of patients that completed the programme, two complete pathological remissions were observed and 5 patients had only microfoci of tumour. No toxic death or grade III-IV toxicities were observed. Mild or moderate side-effects included mucositis, nausea/vomiting and leucopenia. In conclusion, our results indicate that the addition of radiotherapy to pre-operative chemotherapy did not significantly enhance the incidence of pathological complete remissions. New primary treatment approaches should be explored in this subset of patients in order to improve outcome.

Adult↗
PubMed1998

p53 mutations and DNA ploidy in colorectal adenocarcinomas.

The p53 tumour suppressor gene has an important role in the the maintenance of genome stability and its mutational inactivation may be at the origin of aneuploidy in cancer cells. The aim of this study was to determine whether p53 mutations were associated to DNA aneuploidy, as assessed by flow cytometry, in colorectal adenocarcinomas. Analysis of p53 mutations spectrum of the sorted nuclei was done by Denaturing Gradient Gel Electrophoresis (DGGE) and DNA sequencing. Overall, we studied 20 adenocarcinomas, the corresponding control mucosa, and 7 lymph node metastases. Five tumours (25%) were DNA diploid, while 15 tumours (75%) were composed of DNA aneuploid and diploid subpopulations. DNA diploid control mucosa and adenocarcinomas showed no p53 mutations, while 60% of the tumours with DNA aneuploidy had p53 mutations. Therefore, p53 mutations occurred significantly more often in DNA aneuploid than in DNA diploid tumours (p < 0.04, Fisher's exact test). Incidences of DNA aneuploidy and p53 mutations in lymph node metastases were 60 and 86%, respectively. In all tumours showing a p53 mutation, the wild-type allele was not or only bearly visible in DNA aneuploid cells suggesting that, in such cells, aneuploidy is accompanied by complete p53 functional inactivation. The present observations suggest that p53 mutations may have a role in the origin of aneuploidy at late stages of colorectal carcinogenesis.

Adenocarcinoma↗