Search

Aims and Background: In 2002, a survey including 1759 patients treated from 1980 to 1998 established a "benchmark" Italian data source for prostate cancer radiotherapy. This report updates the previous one., Methods: Data on clinical management and outcomes of 3001 patients treated in 15 centers from 1999 through 2003 were analyzed and compared with those of the previous survey., Results: Significant differences in clinical management (-10% had abdominal magnetic resonance imaging; +26% received ≥70 Gy, +48% conformal radiotherapy, -20% pelvic radiotherapy) and in G3-4 toxicity rates (-3.8%) were recorded. Actuarial 5-year overall, disease-specific, clinical relapse-free, and biochemical relapse-free survival rates were 88%, 96%, 96% and 88%, respectively. At multivariate analysis, D'Amico risk categories significantly impacted on all the outcomes; higher radiotherapy doses were significantly related with better overall survival rates, and a similar trend was evident for disease-specific and biochemical relapse-free survival; cumulative probability of 5-year late G1-4 toxicity was 24.8% and was significantly related to higher radiotherapy doses (P <0.001)., Conclusions: The changing patterns of practice described seem related to an improvement in efficacy and safety of radiotherapy for prostate cancer. However, the impact of the new radiotherapy techniques should be prospectively evaluated.

Purpose of Investigation: To add to the existing outcome data regarding radical radiotherapy (RT) for FIGO Stage I and II cervical cancer in a mono-institutional series and to evaluate the cost-benefit ratio of the addition of brachytherapy (BRA) to external-beam radiotherapy (EBRT)., Materials and Methods: The authors report on 240 patients (pts) with FIGO Stage I and II cervical cancer, consecutively treated with radical RT from 1990 through 2009 at the Istituto del Radio "O. Alberti" (EBRT alone, 32, EBRT and BRA, 189, BRA alone, 19). BRA was delivered with low dose rate (LDR, 133.64%) until 2003 and then with high dose rate (HDR, 75.36%). RT was associated with concomitant chemotherapy (CHT), mainly weekly cisplatin 40 mg/m2, in 87 pts, mostly after 2000. The Chi-square test was used to compare the different variables, the Log-Rank test to compare the actuarial survival values, and the Cox-model for the multivariate analysis., Results: Five-year actuarial overall survival (OS) equalled 65%, disease specific survival (DSS) 77%. Regardless of disease stage, better DSS was evident in pts treated with EBRT and BRA compared with those treated with EBRT alone (82% and 58% respectively, p = 0.005); pts treated with concomitant CHT (dose intensity > or = 50%) and higher RT doses (RT cumulative EQD2 > or = 75 Gy) obtained better DSS. Complete response (CR) rate approached 88.4% (206/233 evaluable pts) and more than half of the subsequent failures (21/36) were in distant sites. Older patients and those given BRA had better OS and DSS, while BRA dose rate did not result related with these outcomes. Chronic G3/G4 toxicity involved more frequently the intestinal/rectal tract than other organs at risk. Rectal and vaginal serious chronic sequelae developed mainly in pts treated with EBRT and BRA and suggest the need for more advanced treatment techniques., Conclusions: the present mono-institutional analysis confirms the efficacy of radical RT for the treatment of cervical cancer and provides support to the role of BRA to obtain better outcomes. An effort to reduce long-term toxicity of the treatment is needed.

Background: The prognosis of cerebral metastases (MTS) is linked to progression of both systemic and local disease. The importance of MTS resection has been already pointed out. The observation of a high mortality for not-neurological causes confirms that the modern treatments allow a significant control of the disease within the nervous system. Nevertheless, management difficulties increase with multiple lesions and in these cases the role of surgery has still to be defined., Materials and Methods: We collected the clinical data of patients operated in two centers for cerebral MTS from lung carcinoma during 8 years. Patient selection for surgery followed definite criteria; the limit for multiple MTS was three. We analyzed the functional and survival outcomes of the cohort., Results and Conclusions: Our series included 242 patients: 105 had multiple MTS. Statistical analysis did not show significant differences in mean survival and outcomes between patients with single and multiple lesions. The decease occurred for neurological causes in 15.7% of cases. The selection of candidates for surgery requires several considerations and entails the success rate of this treatment. In patients with the multiple lesions who fulfilled the selection criteria we observed a nevertheless satisfying success after the operation. Our results imply that surgery may be applied also in selected patients with more diffuse intracranial disease. A pre-operative accurate patient selection is related to acceptable quality-of-life following the operation even in cases of multiple MTS.

In order to evaluate the perceived quality of training and education among young Italian radiation oncologists (age <40), AIRO Giovani (Italian Association of Radiation Oncology-Young Members Working Group) carried out a nationwide online survey in 2011, employing a 63-item-based questionnaire, addressed to physician's self-perception of personal training experience (during decade 2001-2011). Issues explored investigated demographics data, duration/organization/content/characteristics of residency programs, the quality of education in clinical oncology, radiation oncology, management and communication attitudes. A total of 382 questionnaires were sent out to physicians and 217 (56.8%) were returned with 197 (51.6%) appropriately filled in and considered for the analysis. The general perception of education and training is positive in most of the explored fields, however some specific contexts and skills still require optimization (combination therapy, peculiar clinical scenarios, particular radiotherapy technical issues, structural organization of residency programs). The present report is expected to be useful for residents, program directors and scientific societies (such as AIRO), to further continue the effort in the improvement of training in radiation oncology.

Our aim was to survey the opinions of Italian radiation and ENT oncologists regarding the role of postoperative radiotherapy (PRT) and the appropriate dose to be given to patients with remnant larynx (RL) after open partial laryngectomy (OPL). The radio-oncologists (ROs) of the Italian Radiation-Oncologist Association (AIRO) and the ENTs of the Head-Neck Oncology Society (AIOCC-IHNS) were contacted through a SurveyMonkey online interface questionnaire. There were 148 usable responses. The majority of ROs recommended PRT in the case of positive/close margins (R(+)/R(close)) or in the case of initial involvement of thyroid cartilage (pT3(tci)). In the same cases, ENTs prefer a "watch and wait" policy (w&w). Both disciplines recommended w&w in the case of negative margins (R(-)). Finally, the majority of RO s recommended irradiating RL with 62-66 Gy in R(+), with 56-66 Gy (61.4%) in R(close) and with 56-60 Gy (34%) in pT3(tci). In Conclusion, OPL raises new considerations about PRT.

Aim: To evaluate the current treatment of mycosis fungoides (MF) and Sézary syndrome (SS) focusing on the role of radiotherapy (RT), its principles and indications, and the perspectives of the novel irradiation technologies., Background: MF and SS are rare lymphoproliferative diseases whose incidence is increasing. For a long time RT has been used as a single modality or in integrated treatment programs for these diseases., Materials and Methods: The latest systematic reviews, primary studies and new diagnostic and treatment guidelines on MF and SS were analyzed. Clinical outcomes together with the technical aspects and the role of RT were also evaluated., Results: New data are available on pathogenesis, diagnostic criteria, classification and staging procedures for MF and SS and several local and systemic therapies are proposed. Localized RT can cure "minimal stage" MF while total skin electron beam irradiation (TSEI) may cure initial-stage disease and may offer important symptom relief (itch, erythroderma) in a more advanced setting. Despite its efficacy, RT is not largely used, mainly because of some technical difficulties but new RT technologies may be proposed to treat large skin surfaces., Conclusions: New treatment programs offer good results, with median survival of more than 12 years in early-stage MF, but the median survival of 2.5 years or less in advanced stages is still a challenge. RT remains an option for all stages with a good cost/effectiveness ratio in a curative or palliative setting. New RT technologies can overcome some technical problems of treating large skin surfaces.

Background: Glutamine synthetase (GS) is an astrocytic enzyme catalyzing the conversion of glutamate and ammonia to glutamine. Its up-regulation has been related to higher tumor proliferation and poor prognosis in extra-cerebral tumors. We have previously reported a GS deficiency in patients with glioblastoma multiforme (GBM) who also developed epilepsy, which is a favorable prognostic factor in glioma. Here, we investigated the prognostic value of GS expression in patients with GBM with or without epilepsy and its correlation with survival., Methods: We conducted a clinical and histopathological study on 83 (52 males) consecutive patients with newly diagnosed GBM. Immunohistochemical expression of GS was scored semi-quantitatively on the basis of cell number, staining intensity, and distribution of immunoreactive cells. Several clinical and neuropathological variables were analyzed in relation to survival and GS expression., Results: Median age at diagnosis was 62 years. At the last evaluation, with a median follow-up of 11.5 months (range, 1.5-58 months), 5 patients (6%) were still alive and 78 (94%) were dead. GS expression patterns in neoplastic cells were inversely correlated to the presence of epilepsy (P < .0001 for intensity and P < .009 for homogeneity of GS distribution, respectively). Univariate analysis showed that RPA score, epilepsy, O6-methylguanine-DNA methyltransferase (MGM)T status, application of Stupp protocol, and GS intensity pattern had a significant impact on survival. Absent/low intensity of GS expression was significantly associated with a longer survival in both uni- (19 vs 8 months; P < .0005) and multivariate (P = .003) analyses., Conclusions: Absent/low-intensity GS expression pattern represents a valuable biomarker of both epilepsy and overall survival in GBM.

Introduction: Medulloblastoma, the most frequent brain tumor in childhood, also occurs with a wide range of characteristics in adult patients. Late relapse is common in adult medulloblastoma, and the overall survival of relapsed patients usually ranges from 12 to 15 months. Treatment at recurrence is still debated and after reoperation includes stereotactic or normofractionated radiotherapy, and high-dose chemotherapy with autologous bone marrow transplantation., Case Presentation: We report on the case of a 31-year-old Caucasian woman who underwent re-irradiation for a recurrence of medulloblastoma at nine years after first irradiation (56Gy), focusing on the radiobiological background and a review of previous studies involving re-irradiation of recurrent medulloblastoma. After surgical excision of the relapsed tumor and medical multi-agent treatment, the site of recurrence was treated using three-dimensional conformal radiotherapy to a total dose of 52.8Gy (1.2Gy/fraction/twice daily). A total biological equivalent dose of 224.6Gy (α:β = 2 Gy) was delivered to the posterior fossa (first and second treatments). No radionecrosis or local recurrence was evident at 18 months after re-irradiation., Conclusion: Re-irradiation can be considered a possible and safe treatment in selected cases of recurrent medulloblastoma in adults. The reported radiobiological considerations could be useful in other cases involving re-irradiation of brain tumors.

Background and Purpose: The mechanism of dissemination of locally advanced head and neck cancer (LAHNC) is far to be resolved. Circulating tumour cells (CTC) have been identified as a prognostic factor in metastatic breast and prostate cancer. This prospective multi-centric analysis studied the possible role of CTC identification in LAHNC., Materials and Methods: CTC were searched in 73 patients with LAHNC (oropharynx, n=39; nasopharynx, n=10; larynx, n=10; paranasal sinuses, n=6, of whom 3 with sinonasal undifferentiated carcinoma, SNUC; hypopharynx, n=5; oral cavity, n=3). All of them (apart from SNUC) had squamous cell cancers. The relationship between CTC positivity and other clinical prognostic factors has been investigated. Response to treatment and survival has been related with changes in CTC number during the treatment., Results: CTC were frequently identified in oro- and hypopharyngeal cancer and in SNUC. They were more frequent in stage IV than in stages I-III disease (18% versus 6%, p=NS (not significant)). Partial or complete response (CR) was related with the absence or disappearance of CTC during treatment (p=0.017). A decrease in the CTC number or their absence throughout the treatment seems also related with non-progressive disease, after both complete or incomplete remission and with the proportion of patients alive and NED (no evidence of disease) (p=0.009)., Conclusions: These preliminary data suggest a possible role of CTC determination in head and neck cancer. Additional and longer follow up data need to be collected to confirm these findings., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Purpose: The authors sought to define treatment results according to the different accrual periods and clinical-therapeutic features in a large series of nasopharyngeal cancer (NPC) patients treated in two Italian centres over more than two decades., Materials and Methods: A total of 883 patients consecutively treated with radiotherapy between 1977 and 2000 at the Florence (FLO) and Brescia (IRA) Radiation Oncology centres were studied. Five-year overall (OS) and disease-specific (DSS) actuarial survival rates in the different pathological, clinical and therapeutic subgroups were calculated, along with the actuarial local-regional control (LRC) probability., Results: At univariate analysis, survival and local control rates were significantly better in the more recent accrual periods and in the more favourable disease presentations; treatment-related parameters mainly affect LRC. At multivariate analysis, patient- and disease-related factors had a more evident prognostic effect than did therapeutic factors, although dose to the nasopharynx and treatment technique had a marginally significant impact on DSS and OS., Conclusions: Results of this benchmark study may be useful for understanding the development of new radio-therapy techniques for NPC, such as three-dimensional conformal radiotherapy (3D-CRT) and particularly intensity-modulated radiotherapy (IMRT).

Purpose: The authors sought to define toxicity patterns according to the different accrual periods and clinical-therapeutic features in a large series of nasopharyngeal cancer (NPC) patients treated in two Italian centres over more than two decades., Materials and Methods: A total of 883 patients consecutively treated with radiotherapy from 1977 to 2000 at the Florence (FLO) and Brescia (IRA) radiation oncology centres were studied. The crude incidence of late treatment toxicity in the different subgroups of patients was calculated and compared., Results: Higher total and fractional doses and the "older" treatment techniques were related with an increased incidence of the main late effects of treatment. More recently treated patients experienced less treatment-related complications., Conclusions: Results of this benchmark study may have implications for understanding and developing new radiotherapy techniques, such as three-dimensional conformal radiotherapy (3D-CRT) and, in particular, intensity-modulated radiotherapy (IMRT) for NPC patients.

Although the evidence for the benefit of adding temozolomide (TMZ) to radiotherapy (RT) is limited to glioblastoma patients, there is currently a trend toward treating anaplastic astrocytomas (AAs) with combined RT + TMZ. The aim of the present study was to describe the patterns of care of patients affected by AA and, particularly, to compare the outcome of patients treated exclusively with RT with those treated with RT + TMZ. Data of 295 newly diagnosed AAs treated with postoperative RT ± TMZ in the period from 2002 to 2007 were reviewed. More than 75% of patients underwent a surgical removal. All the patients had postoperative RT; 86.1% of them were treated with 3D-conformal RT (3D-CRT). Sixty-seven percent of the entire group received postoperative chemotherapy with TMZ (n = 198). One-hundred sixty-six patients received both concomitant and sequential TMZ. Prescription of postoperative TMZ increased in the most recent period (2005-2007). One- and 4-year survival rates were 70.2% and 28.6%, respectively. No statistically significant improvement in survival was observed with the addition of TMZ to RT (P = .59). Multivariate analysis showed the statistical significance of age, presence of seizures, Recursive Partitioning Analysis classes I-III, extent of surgical removal, and 3D-CRT. Changes in the care of AA over the past years are documented. Currently there is not evidence to justify the addition of TMZ to postoperative RT for patients with newly diagnosed AA outside a clinical trial. Results of prospective and randomized trials are needed.

Purpose: Recursive partitioning analysis (RPA) is a prognostic index capable of predicting survival in patients with brain metastases. Histology of the primary tumour has only recently been introduced among the factors that could potentially affect the prognosis of these patients. The main purpose of this study was to analyse the impact of RPA in correlation with histology of the primary tumour in patients with brain metastases treated with hypofractionated radiotherapy., Materials and Methods: A total of 382 patients were treated at the Department of Radiotherapy of Brescia University, and RPA classes were retrospectively assigned to all patients. Univariate and multivariate analyses were then performed to verify the role of the single prognostic variables, for the entire group and for each prognostic class, as well as in correlation with histology of the primary tumour., Results: Most patients were classified as RPA prognostic class 2 (48%). The majority of patients was treated with a total dose of 30 Gy delivered in ten fractions, whereas the dose of 20 Gy in four or five fractions was primarily used in patients classified as RPA class 3. At univariate analysis, the main variable correlating with overall survival (OS) was RPA class (p=0.000). Uni- and multivariate analysis performed on RPA class 1 patients only confirmed the role of general performance status, number of metastases and total radiotherapy dose for predicting OS. In the group with the worst prognosis (RPA class 3), none of the variables had a statistically significant role in improving OS. Tumour histology and radiotherapy dose influence OS, even in RPA class 1 and 2 patients., Conclusions: This analysis confirms that RPA prognostic class is the factor that most predicts survival. Primary tumour histology helps determine prognosis, especially in RPA prognostic classes 1 and 2. As regards RPA class 3, no factor influences survival prognosis.

Purpose: Individual variability in radiosensitivity is large in cancer patients. Single nucleotide polymorphisms (SNPs) in genes involved in DNA repair and in protection against reactive oxygen species (ROS) could be responsible for such cases of radiosensitivity. We investigated the association between the occurrence of acute reactions in 101 patients with squamous cell carcinoma of the head and neck (SCCHN) after radiotherapy (RT) and five genetic polymorphisms: XRCC1 c.1196A>G, XRCC3 c.722C>T, RAD51 (c.-3429G>C, c.-3392G>T), and GSTP1 c.313A>G., Materials and Methods: Genetic polymorphisms were detected by high resolution melting analysis (HRMA). The development of acute reactions (oral mucositis, skin erythema and dysphagia) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for biologically effective dose (BED)., Results: Development of grade ≥2 mucositis was increased in all patients (chemo-radiotherapy and radiotherapy alone) with XRCC1-399Gln allele (HR=1.72). The likelihood of developing grade ≥2 dysphagia was higher in carriers of RAD51 c.-3429 CC/GC genotypes (HR=4.00). The presence of at least one SNP or the co-presence of both SNPs in XRCC1 p.Gln399Arg /RAD51 c.-3429 G>C status were associated to higher likelihood of occurrence of acute toxicities (HR=2.03)., Conclusions: Our findings showed an association between genetic polymorphisms, XRCC1 c.1196A>G and RAD51 c.-3429 G>C, and the development of radiation-induced toxicities in SCCHN patients., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: To investigate the pattern of care and outcomes for newly diagnosed glioblastoma in Italy and compare our results with the previous Italian Patterns of Care study to determine whether significant changes occurred in clinical practice during the past 10 years., Methods: Clinical, pathological, therapeutic, and survival data regarding 1059 patients treated in 18 radiotherapy centers between 2002 and 2007 were collected and retrospectively reviewed., Results: Most patients underwent both computed tomography and magnetic resonance imaging either preoperatively (62.7%) or postoperatively (35.5%). Only 123 patients (11.6%) underwent a biopsy. Radiochemotherapy with temozolomide was the most frequent adjuvant treatment (70.7%). Most patients (88.2%) received 3-dimensional conformal radiotherapy. Median survival was 9.5 months. Two- and 5-year survival rates were 24.8% and 3.9%, respectively. Multivariate analysis showed the statistical significance of age, postoperative Karnofsky Performance Status scale score, surgical extent, use of 3-dimensional conformal radiotherapy, and use of chemotherapy. Use of a more aggressive approach was associated with longer survival in elderly patients. Comparing our results with those of the subgroup of patients included in our previous study who were treated between 1997 and 2001, relevant differences were found: more frequent use of magnetic resonance imaging, surgical removal more common than biopsy, and widespread use of 3-dimensional conformal radiotherapy + temozolomide. Furthermore, a significant improvement in terms of survival was noted (P < .001)., Conclusion: Changes in the care of glioblastoma over the past few years are documented. Prognosis of glioblastoma patients has slightly but significantly improved with a small but noteworthy number of relatively long-term survivors.

Barrett's oesophagus (BO) is the primary precursor lesion for oesophageal adenocarcinoma (ADC). The natural history of metaplasia-dysplasia-carcinoma sequence remains largely unknown. HER2/neu oncogene results overexpressed/amplified in preneoplastic lesions and in ADC of the oesophagus and it has been associated with poor prognosis. Our aim was to evaluate the role of HER2 overexpression/amplification in predicting the conversion from precursor lesions to ADC. We retrospectively evaluated by univariate analysis of single variables clinical records and histological specimens of 21 patients with a confirmed diagnosis of BO and/or oesophageal dysplasia. Clinical variables included age, gender, alcohol and smoking intake, presence of symptoms (pyrosis, disphagia) and endoscopic features (length). HER2 status was studied by immunohistochemistry and fluorescence in situ hybridization (FISH) on paraffin-embedded tissue. The end-points were the occurrence of progression and the time-to-progression (TTP) from the initial histologic lesion to the worst pathological pattern. Median age at diagnosis was 63 years (range 37-84). BO median length was 4.5 cm. Progression occurred in 11 of 21 patients and median TTP was 24 months. HER2 was overexpressed/amplified in 8 of 21 (38%) patients. HER2 overexpression/ amplification and the presence of dysplasia were statistically associated with progression (P= 0.038). This study provides evidence for a possible role of HER2 in the transition from dysplasia to ADC of the oesophagus. This fact could help in identifying patients at high risk of malignant transformation.

Introduction: Patients with metastatic mucoepidermoid carcinoma of salivary glands have a poor outcome. The epidermal growth factor receptor protein is overexpressed in approximately 70% of mucoepidermoid carcinoma patients and may represent a therapeutic target. However, whether treatment with anti-epidermal growth factor receptor agents is effective is unclear and clinical trials are difficult due to the rarity of the disease. Here we assessed the activity of cetuximab in mucoepidermoid carcinoma on a molecular basis., Case Presentation: We present the case of a 40-year old Caucasian man with a mucoepidermoid carcinoma of the major salivary glands who developed distant bone and visceral metastases despite platinum-based chemotherapy. Epidermal growth factor receptor was overexpressed and fluorescence in situ hybridization analysis demonstrated a chromosome 7 polysomy. The patient was treated with the monoclonal antibody cetuximab in combination with cisplatin. After 11 doses of cetuximab, the patient developed brain metastases but evidence of response was documented at all extracranial metastatic sites., Conclusion: This case report indicates that cetuximab can be active in mucoepidermoid carcinoma and may restore sensitivity to cisplatin in platinum-treated patients. Cetuximab does not cross the blood brain barrier and may select a metastatic clone to home the central nervous system while responding at other sites.

Purpose: The purpose of this article is to illustrate a case where acquisition of digital imaging know-how by a modern radiotherapy division has helped to solve a technical problem while allowing substantial savings through the use of free and open-source resources. The problem was related to the necessity to route, with complex policies, the images produced by different digital imaging and communications in medicine (DICOM) sources within the department or in other divisions and/or hospitals., Materials and Methods: The problem was solved by using completely free, well-tested and stable technologies (PHP, Apache, MySQL, DCMTK OFFIS, Red Hat Linux 9A and Linux Fedora Core 4) and low-cost hardware to contain costs. In the development, we also considered integration of the routed images with the existing electronic clinical records., Results: The system developed, called the dicom router, implemented two kinds of routing: manual and automatic, both oriented to link the images acquired with the existing electronic clinical records. System stability was enhanced in a second phase by using a low-cost hardware redundancy solution. The system has now been operating for 1 year and has proved the value of the technologies used., Conclusions: The need to operate with more than one provider creates a series of integration issues, so that it becomes economically appealing to acquire internally the knowledge needed to interact more precisely with providers of big information technology (IT) solutions. This need is well catered for by open-source technologies, which are well documented and available to everyone. By using them, in-house IT technicians are able to implement valuable technical solutions for small-to medium-sized informatization problems, which would otherwise remain unsolved except with great economic efforts.

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.

Aims: To contribute to the available evidence about the efficacy of exclusive radiotherapy for bladder cancer through a retrospective analysis of a large series of patients consecutively treated in a single institution., Materials and Methods: A total of 459 patients with UICC categories T1-T4, N0-Nx and M0 bladder cancer consecutively treated with radiotherapy alone with radical intent formed the clinical basis for this study. Many of them (and particularly the T1 cases) had poor medical conditions or were unfit for surgery. About half of the cases (54%) had a T2 tumour, and about 18% had T3-T4 disease. Eighty per cent of the cases received minimal doses in the target volume in the range 60-70 Gy; pelvic lymph nodes were treated in 34%. Simple radiotherapy techniques were used in most cases. Average follow-up for living patients was 4.4 years. Results were analysed according to number and type of relapses: overall survival, disease-specific survival, failure-free survival probability, acute and late toxicity (RTOG scale)., Results: Actuarial 5-year overall survival, disease-specific survival and failure-free survival rates at 5 years for the entire series were 36%, 56%, 33%, respectively. Age, T category (for all the end points) and tumour dose (only for failure-free survival) were significantly related to prognosis at multivariate survival analysis. Late enteric toxicity (6.1% of the cases) was significantly linked with the treated volumes (univariate analysis). Urinary late toxicity (23% of cases) was linked with age and T category (multivariate analysis). In both cases, toxicity was mostly Grade 1 or 2., Conclusions: The results of radiotherapy in this negatively selected series, accrued over a long period of time in patients treated with unsophisticated techniques, are reasonably good; they add to the evidence available to support the use of modern bladder-sparing programmes, including the association of chemo- and radiotherapy.

Purpose: To retrospectively evaluate local control rates, late damage incidence, functional results, and second tumor occurrence according to the different patient, tumor, and treatment features in a large bi-institutional series of T1 glottic cancer., Methods and Materials: A total of 831 T1 glottic cancer cases treated consecutively with radical intent at the Florence University Radiation Oncology Department (FLO) and at the Radiation Oncology Department of the University of Brescia-Istituto del Radio "O. Alberti" (BS) were studied. Actuarial cumulative local control probability (LC), disease-specific (DSS), and overall survival (OS) rates have been calculated and compared in the different clinical and therapeutic subgroups with both univariate and multivariate analysis. Types of relapse and their surgical salvage have been evaluated, along with the functional results of treatment. Late damage incidence and second tumor cumulative probability (STP) have been also calculated., Results: In the entire series, 3-, 5-, and 10-year OS was equal to 86%, 77%, and 57%, respectively. Corresponding values for LC were 86%, 84%, and 83% and for DSS 96%, 95%, and 93%, taking into account surgical salvage of relapsed cases. Eighty-seven percent of the patients were cured with function preserved. Main determinants of a worse LC at univariate analysis were: male gender, earlier treatment period, larger tumor extent, anterior commissure involvement, and the use of Cobalt 60. At multivariate analysis, only gender, tumor extent, anterior commissure involvement, and beam type retained statistical significance. Higher total doses and larger field sizes are significantly related (logistic regression) with a higher late damage incidence. Scatterplot analysis of various combinations of field dimensions and total dose showed that field dimensions >35 and <49 cm2, together with doses of >65 Gy, offer the best local control results together with an acceptably low late damage incidence. Twenty-year STP was equal to 23%, with second tumor deaths being more frequent than larynx cancer deaths (67 of 831 vs. 46/831)., Conclusion: The results of this study support the opinion, suggested by some international guidelines, that radiotherapy is standard treatment for T1 glottic cancer. Better results are obtained in patients with less extended disease and with 4-6 MV photon beams. The use of doses in excess of 65 Gy and of field sizes of 36-49 cm2 is probably the best technical choice available. Late damage is infrequent, but careful follow-up is warranted to detect early not only relapses (because conservative salvage surgery is feasible), but also second malignant tumors, which constitute the main cause of death in these patients and are potentially curable.

Purpose: To retrospectively evaluate local control rates, late damage incidence, functional results, and second-tumor occurrence according to the different patient, tumor, and treatment features in a large bi-institutional series of T2 glottic cancer., Methods and Materials: A total of 256 T2 glottic cancer cases treated consecutively with radical intent at the Florence University Radiation Oncology Department (FLO) and at the Radiation Oncology Department of the University of Brescia, Istituto del Radio "O. Alberti" (BS) were studied. Cumulative probability of local control (LC), disease-specific survival (DSS), and overall survival (OS) rates were calculated and compared in the different clinical and therapeutic subgroups by both univariate and multivariate analysis. Types of relapse and their surgical salvage were evaluated, along with the functional results of treatment. Late-damage incidence and second-tumor cumulative probability (STP) were also calculated., Results: In the entire series, 3-year, 5-year, and 10-year OS rates were, respectively, 73%, 59%, and 37%. Corresponding values for cumulative LC probability were 73%, 73%, and 70% and for DSS, 89%, 86%, and 85%, taking into account surgical salvage of relapsed cases. Seventy-three percent of the patients were cured with function preserved. Main determinants of a worse LC at univariate analysis were larger tumor extent and impaired cord mobility. At multivariate analysis, the same factors retained statistical significance. Twenty-year STP was 23%, with second-tumor deaths less frequent than larynx cancer deaths (20 of 256 vs. 30 of 256). Incidence of late damage was higher in the first decade of accrual (22%) than in the last decade (10%, p = 0.03); the same was true for severe late damage (9% vs. 1.8%)., Conclusion: Present-day radical radiotherapy can be considered a standard treatment for T2 glottic cancer. Better results are obtained in patients with less extended disease. Late damage is relatively infrequent, but a careful follow-up is warranted for early detection not only of relapses (because salvage surgery is feasible) but also of second malignant tumors, which constitute a relevant but not the leading cause of death in these patients and are potentially curable.

Purpose: To retrospectively analyze the outcome and patterns of relapse in localized extranodal non-Hodgkin's lymphoma of the head and neck (HN-NHL) after radiotherapy alone or combined modality treatment., Patients and Methods: A retrospective analysis of 107 patients with HN-NHL was performed. Relapse patterns, overall survival (OS) and relapse-free survival (RFS) were analyzed. Only stage I (n=50) and stage II (n=57) patients were included with either low-grade (n=21) or high-grade (n=86) lymphoma. Fifty-nine patients were treated with radiotherapy (RT) alone and 48 patients received combined-modality treatment (CMT) consisting of chemotherapy (CHOP or CHOP-like) followed by radiotherapy. The volumes of irradiation included local field (n=24), involved field (n=13) and extended field (n=70). The median age at diagnosis was 63 years (range, 17-86 years)., Results: The overall response rates (CR+PR) in the radiotherapy group and the combined modality group were 100% and 96%, respectively. With a median follow-up of 49.4 months, 29 of 59 patients after RT alone (37%) and 30 of 48 patients after CMT (62%) were disease-free. In the whole series the projected five-year OS and RFS were 58.7% and 61.8%. At univariate analysis of clinical variables with potential impact on survival including age, stage, histology, IPI score, single or combined treatment and volumes of irradiation, only age and, to a limited extent, type of treatment influenced OS (age < or =60 years 79%, >60 years 41%, P < 0.001; RT alone 54.9%, CMT 62.8%, P = 0.0487) and RFS (< or =60 years 75%, >60 years 50%, P < 0.001; RT alone 54%, CMT 71%, P = 0.039). Better OS and RFS rates were obtained in patients with stage II and high-grade disease treated with CMT (five-year OS and RFS 63% and 69%, respectively; the corresponding values for RT alone were 38% and 34%). The final model of the multivariate analysis retained only age (< or =60 years) as a significant prognostic factor for both RFS and OS (P < 0.001). In the whole series, the sites of relapse were mainly systemic (n = 32/40, 80%) and in-field relapses were rare (n = 3/40, 7.5%)., Conclusion: HN-NHL is characterized by a high risk of relapse, particularly at distant sites. Older patients have a significantly worse prognosis. Radiotherapy offers a very good local control rate although combined modality treatment possibly produces better RFS and OS, especially for stage II and high-grade disease. Better systemic approaches are warranted for a more consistent impact on survival in this particular subset of extranodal lymphoma. However, radiotherapy alone may offer a feasible and effective modality for patients who cannot tolerate more aggressive treatments. Extended-field radiotherapy and the treatment of a larger number of uninvolved lymph nodal regions does not confer a RFS or OS advantage, either after RT alone or after CMT.

Ureteral stenosis secondary to radiation-induced fibrosis is a well-known, late complication of radiation treatment in patients with carcinoma of the uterine cervix. This paper focuses on epidemiological data, physiopathology and treatment modalities reviewed from Internet-published literature. Experience from a single institution (Institute of Radiotherapy of Brescia) is reported. Ureteral stenosis has an incidence of 15% in patients treated with standard doses of radiotherapy for carcinoma of the uterine cervix. An asymptomatic low-grade fibrotic ureteral stenosis establishes at doses of 20 Gy in experimental animal models, and both incidence and severity rise with increasing of doses. An emerging role for Transforming Growth Factor beta 1 (TGF-beta 1) is recognized in determining chronic activation of fibroblast/fibrocyte lineage and remodelling extracellular matrix which are known mechanisms in the genesis of any fibrotic disease. Experience of the radiotherapy Institute of Brescia, Italy, is reported. A series of 191 patients with stage IB-IIA cervix carcinoma was treated with radical radiotherapy. About 10% of patients developed late urinary tract complications related to post-actinic fibrosis with only 1% of grade III-IV ureteral fibrosis. These data are consistent with those published by other institutions. In conclusion, late ureteral fibrosis is a common and distressing treatment-related complication in patients treated with radiotherapy for cervix carcinoma. Newer strategies in better defining the target for radiotherapy, conformational radiotherapy and better understanding of biologic factors will contribute to further reducing the frequency of such a complication.

Purpose: In the mid-late life, basal laminar drusen can be associated with vitelliform macular degeneration and choroidal neovascularization. The differential diagnosis between these two clinical entities is not always easy with fluorescein angiography. The aim of this case report is to describe the indocyanine green angiographic features of basal laminar drusen and pseudo-vitelliform material and to evaluate the role of ICG angiography in differentiating new choroidal vessels from vitelliform macular degeneration., Patients and Methods: Six patients (12 eyes) with central visual loss and metamorphopsia underwent a biomicroscopic examination. Diagnosis was basal laminar drusen and bilateral vitelliform macular degeneration. Fluorescein and indocyanine green angiographies were performed and the results were compared., Results: In all eyes, basal laminar drusen were hyperfluorescent with both angiographies. On fluorescein angiography, the macular material was hypofluorescent early, but gradual staining occurred from the borders in the late phase. In 8 out of the 12 eyes, fluorescein angiographic characteristics of the macular lesions could not provide clues to differential diagnostic between new choroidal vessels and vitelliform material. On indocyanine green angiography, in 8 eyes the material remained intensely hypofluorescent during the whole sequence. In 4 eyes, indocyanine green angiography allowed the identification of hyperfluorescent well-defined new choroidal vessels., Conclusions: Indocyanine green angiography allows the visualization of basal laminar drusen and can easily differentiate choroidal neovascularization from acquired vitelliform degeneration.