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Publications and source records attributed to Umberto Ricardi.
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Mantle Cell Lymphoma (MCL) is a well-known histological and clinical subtype of B-cell non-Hodgkin's Lymphomas. It is usually characterized by an aggressive disease course, presenting with advanced stage disease at diagnosis and with low response rates to therapy. However few cases of indolent course MCL have been described. We herein report a case of MCL with splenomegaly and peripheral blood involvement as main clinical features. The patient underwent moderate dose splenic radiation therapy and achieved spleen downsizing and peripheral blood complete remission. Splenic irradiation has been extensively used in the past as palliative treatment in several lymphoproliferative disorders and a systemic effect and sometimes peripheral blood complete remissions have been observed. Mainly advocated mechanisms responsible for this phenomenon are considered direct radiation-induced apoptotic cell death, immune modulation via proportional changes of lymphocyte subsets due to known differences in intrinsic radiosensitivity and a radiation-induced cytokine release. The peculiar intrinsic radiosensitivity pattern of lymphoid cells could probably be explained by well-defined individual genetic and molecular features. In this context, among NHLs, MCL subtype has the highest rate of ATM (Ataxia Teleangiectasia Mutated) inactivation. While the ATM gene is thought to play a key-role in detecting radiation-induced DNA damage (especially Double Strand Breaks), recent in vitro data support the hypothesis that ATM loss may actually contribute to the radiosensitivity of MCL cells. ATM status was retrospectively investigated in our patient, with the tool of Fluorescence In Situ Hybridization, showing a complete inactivation of a single ATM allele secondary to the deletion of chromosomal region 11q22-23. The presence of this kind of cytogenetic aberration may be regarded in the future as a potential predictive marker of radiation response.
BACKGROUND AND PURPOSE: A survey was conducted of radiotherapy (RT) resources and utilization in a northwestern Italian Region in order to assess geographical variations in radiotherapy utilization rates, and the effects of infrastructure supply on accessibility. MATERIALS AND METHODS: The survey was conducted by analysing standardized utilization rates based on administrative records. The data were analysed at both Regional and Local Health Unit (LHU) level. RESULTS: Wide variation was found among LHUs RT utilization rates--the sex- and age-standardized rates varied from 1.8/1000 inhabitants to more than 3/1000 inhabitants. Patients resident in LHUs with no RT service showed a lower probability of accessing RT (standardized rate ratio (SRR), 0.82; 95%IC, 0.80-0.85). The utilization rate decreased in relation to the distance between a patient's residence and the nearest RT service; the reduction was greater for patients > or =70 years of age. CONCLUSION: The wide geographic variation implies lack of equity in access to services. Utilization levels decreased significantly with increasing distance from the nearest RT service, distance being a barrier to access particularly for older persons. The heterogeneous distribution of services on the Regional territory seems a relevant explanation of differences in utilization rates.
PURPOSE: To analyze the patterns of practice and survival in a series of 1722 adult astrocytoma patients treated in 12 Italian radiotherapy centers. METHODS AND MATERIALS: A total of 1722 patients were treated with postoperative radiotherapy (90% World Health Organization [WHO] Grade 3-4, 62% male, 44% aged >60 years, 25% with severe neurologic deficits, 44% after gross total resection, 52% with high-dose radiotherapy, and 16% with chemotherapy). Variations in the clinical-therapeutic features in three subsequent periods (1985 through 2001) were evaluated, along with overall survival for the different subgroups. RESULTS: The proportion of women, of older patients, of those with worse neurologic performance status (NPS), with WHO Grade 4, and with smaller tumors increased with time, as did the proportion of those treated with radical surgery, hypofractionated radiotherapy, and more sophisticated radiotherapy techniques, after staging procedures progressively became more accurate. The main prognostic factors for overall survival were age, sex, neurologic performance status, WHO grade, extent of surgery, and radiation dose. CONCLUSIONS: Recently, broader selection criteria for radiotherapy were adopted, together with simpler techniques, smaller total doses, and larger fraction sizes for the worse prognostic categories. Younger, fit patients are treated more aggressively, more often in association with chemotherapy. Survival did not change over time. The accurate evaluation of neurologic status is therefore of utmost importance before the best treatment option for the individual patient is chosen.
The Gafchromic EBT was recently introduced in film dosimetry for external beam therapy (EBT). The high spatial resolution, weak energy dependence, and near-tissue equivalence of EBT films make them suitable for measurement of dose distributions in radiotherapy, especially intensity-modulated radiation therapy (IMRT). Starting with a sensitometric curve and dose uncertainty relative to the flatbed scanner, the goal of this study was to find an efficient method of correcting for light scattering, and to compare dose distribution supplied by Gafchromic EBT with the distribution obtained with a 2D ion-chamber detector system. Light scattering was analyzed for different levels of dose, and was found to depend on the red-scale value as well as the position of the pixel on the scanner. Many "uniform" films were exposed at different levels of dose to create a two-dimensional matrix correction to take this effect into account. The dose distribution obtained for three clinical beams (10 x 10, 15 x 15 cm open fields and 12 x 12 cm wedge 60 degrees field) were in agreement with those supplied by the 2D array. Gamma index <1 (using 5 mm distance and 5% dose as constraints) for the three fields considered was reached in an average of 98% of the points.
In this study the authors retrospectively evaluated the feasibility and effectiveness of prolonged oral etoposide therapy in children with recurrent ependymoma. Twelve ependymoma patients with documented recurrent or persistent disease were treated between May 1998 and October 2003. All patients were treated monthly with oral VP-16 administered at a dose of 50 mg/m2/d for 21 days, with a 7-day interval between cycles, for a planned minimum number of six cycles. Response (complete plus partial) after two cycles occurred in 5 of the 12 patients (41.6%). Response plus stable disease occurred in 10 of the 12 (83.3%), with a median duration of response or stable disease of 7 months (range 4-30). The median survival was 7 months; the 2-year progression-free survival was 16.7%. These results emphasize that oral etoposide is an attractive option for childhood recurrent ependymomas in terms of administration, tolerability, and neuroradiologic response.
PURPOSE: A postsurgical "stage-based" protocol for ependymoma was designed. METHODS AND MATERIALS: Children were given: (1) focal hyperfractionated radiotherapy (HFRT) if with no evidence of disease (NED), or (2) 4 courses with VEC followed by HFRT for residual disease (ED). HFRT dose was 70.4 Gy (1.1 Gy/fraction b.i.d.); VEC consisted of VCR 1.5 mg/m2 1/w, VP16 100 mg/m2/day x 3, CTX 3 g/m2 d 1. When feasible, second-look surgery was recommended. RESULTS: Sixty-three consecutive children were enrolled: 46 NED, 17 ED; the tumor was infratentorial in 47 and supratentorial in 16, with spinal metastasis in 1. Of NED patients, 35 of 46 have been treated with HFRT; 8 received conventionally fractionated radiotherapy, and 3 received no treatment. Of the 17 ED patients, 9 received VEC + HFRT; violations due to postsurgical morbidity were as follows: HFRT only (2), conventionally fractionated radiotherapy (3) + VEC (2), and no therapy (1). Objective responses to VEC were seen in 54%; objective responses to RT were seen in 75%. Overall survival and progression-free survival at 5 years for all 63 children were 75% and 56%, respectively; for the NED subgroup, 82% and 65%; and for the ED subgroup, 61% and 35%, respectively. All histologies were centrally reviewed. At multivariate analysis, grading, age, and site proved significant for prognosis. CONCLUSIONS: HFRT, despite the high total dose adopted, did not change the prognosis of childhood ependymoma as compared to historical series: New radiotherapeutic approaches are needed to improve local control. Future ependymoma strategies should consider grading when stratifying treatment indications.
AIMS AND BACKGROUND: Brachytherapy for prostate cancer by means of permanently implanted 125I sources is a well established procedure. An increasing number of patients all over the world are treated with this modality. When the technique was introduced at our institution, radiation protection issues relative to this technique were investigated in order to comply with international recommendations and national regulations. Particular attention was paid to the need for patient shielding after discharge from hospital. METHODS: The effective and equivalent doses to personnel related to implantation, the effective dose to patient relatives as computed by a developed algorithm, the air kerma strength values for the radioactive sources certified by the manufacturer compared with those measured by a well chamber, and the effectiveness of lead gloves in shielding the hands were evaluated. RESULTS: The effective dose to the bodies of personnel protected by a lead apron proved to be negligible. The mean equivalent doses to the physician's hands was 420 microSv for one implant; the technician's hands received 65 microSv. The mean air kerma rate measured at the anterior skin surface of the patient who had received an implant was 55 microGy/h (range, 10-115) and was negligible with lead protection. The measured and certified air kerma strength for125I seeds in RAPID Strand corresponded within a margin of +/- 5%. The measured attenuation by lead gloves in operative conditions was about 80%. We also defined the recommendations to be given to the patient at discharge. CONCLUSIONS: The exposure risks related to brachytherapy with 125I to operators and public are limited. However, alternation of operators should be considered to minimize exposure. Patient-related measurements should verify the dose rate around the patient to evaluate the need for shielding and to define appropriate radiation protection recommendations.
AIMS AND BACKGROUND: In October 1995, the Piedmont AIRO (Italian Society of Radiation Oncology) Group started a multi-institutional study of radiochemotherapy on locally advanced esophageal cancer, characterized by external radiotherapy followed by an intraluminal high dose-rate brachytherapy boost. Most patients were re-evaluated for surgery at the end of the program. The primary aim of the study was to assess efficacy of curative radiochemotherapy regarding overall survival and local control rates. The secondary aim was to evaluate the ability of radiochemotherapy to make resectable lesions previously considered inoperable. METHODS AND STUDY DESIGN: Between January 1996 and March 2000, 75 patients with locally advanced esophageal cancer were enrolled. All were treated with definitive radiotherapy; due to age or high expected toxicity, chemotherapy was employed only in 53 of them. Treatment schedule consisted of 60 Gy external radiotherapy (180 cGy/d, 5 days/week for 7 weeks) concomitant with two 5-day cycles of chemotherapy with cisplatin and fluorouracil (weeks 1 and 5). One or two sessions of 5-7 Gy intraluminal high dose-rate brachytherapy were carried out on patients whose restaging showed a major tumor response. Surgery was performed in 14 patients. RESULTS: At the end of radiotherapy, dysphagia disappeared in 46/75 cases (61%), and in 20/75 (27%) a significant symptom reduction was recorded. Complete objective response at restaging after radiotherapy was obtained in 33% of patients and a partial response in 53%. At the end of the multimodal treatment program, including esophagectomy, complete responses were 34 (45%); 4 of 14 (28.5%) cases proved to be disease free (pT0) at pathological examination. No G3-G4 toxicity was recorded. Two- and 5-year overall survival rates of all patients were, respectively, 38% and 28%; 2- and 5-year local control rates were, respectively, 35% and 33%. In a subgroup of 20 nonsurgical patients in complete response after radiochemotherapy, the overall survival rate at 3 and 5 years was 65% and the local control rate at 3 and 5 years was 75%. According to multivariate analysis, prognostic factors for survival were Karnofsky index and esophagectomy. CONCLUSIONS: For patients with locally advanced disease, radiochemotherapy showed improved clinical and pathologic tumor response and survival compared to surgery or radiotherapy alone. Intraluminal brachytherapy with a small fraction size allows an increased dose to the tumor without higher toxicity. Esophagectomy following radiochemotherapy could improve survival rates compared to definitive radiochemotherapy, but it is necessary to optimize selection criteria for surgery at the re-evaluation phase.
New insights into molecular mechanisms responsible for cellular radiation response are coming from recent basic radiobiological studies. Preliminary data supporting the concept of clinical radiosensitivity as a complex genetically controlled event are available, and it seems reasonable to hypothesize that genes encoding for proteins implicated in known radiation-induced pathways, such as DNA repair, could influence normal tissue and tumor response to radiotherapy. Such genes could be considered as candidates for experimental studies and as targets for innovative therapies. Variants that could influence individual radiosensitivity have been recently identified, and specific Single Nucleotide Polymorphisms have been associated to the development of different radiation effects on normal tissues. Allelic architecture of complex traits able to modify phenotypes is difficult to be established, and different grades of interaction between common or rare genetic determinants may be present and should be considered. Many different experimental strategies could be investigated in the future, such as analysis of multiple genes in large irradiated patient cohorts strictly observed for radiation effects or identification of new candidate genes, with the aim of identifying factors that could be employed in predictive testing and individualization of radiation therapy on a genetic basis.
We report the case of a 63-year-old man with a clearly established diagnosis of hairy cell leukemia, treated with multiple lines of chemotherapy, who complained of localized pain in the left humerus. Radiological findings showed a dystrophic-blastic area within the humeral head. Fine-needle biopsy confirmed the hypothesis of bone involvement of hairy cell leukemia. The patient underwent radiotherapy at a dose of 25 Gy, obtaining a complete clinical response with resolution of pain and a partial recovery of the normal radiological structure of the humerus after 2 months. In addition to the case report, we present a short review of the literature focusing on the role of radiotherapy in this subset of patients.
In radiobiology, the hypoxic cells have been shown to be more resistant to irradiation as compared to cells irradiated in conditions of normal oxygenation. Moreover, most solid tumors contain foci of clonogenic cells able to cause the failure of radiotherapy and the development of more aggressive phenotypes. To-date, numerous techniques allow the detection and quantitation of tumor hypoxia in many tumors and to correlate it with the clinical course. The impact of tumor hypoxia is evident from a careful analysis of data of several trials where the solution of the problem was attempted. In recent years, new functional imaging procedures, assays of molecular biology and new drugs that act directly on hypoxic cells, have been introduced. In the near future, this might lead to the control of this negative clinical impact of hypoxia.