Validation of RayStation Monte Carlo dose calculation algorithm for multiple LINACs.

PURPOSE: A photon Monte Carlo (MC) model was commissioned for flattened (FF) and flattening filter free (FFF) 6 MV beam energy. The accuracy of this model, as a single model to be used for three beam matched LINACs, was evaluated. METHODS: Multiple models were created in RayStation v.10A for three linacs equipped with Elekta "Agility" collimator. A clinically commissioned collapsed cone (CC) algorithm (GoldCC), a MC model automatically created from the CC algorithm without further optimization (CCtoMC) and an optimized MC model (GoldMC) were compared with measurements. The validation of the model was performed by following the recommendations of IAEA TRS 430 and comprised of basic validation in a water tank, validation in a heterogeneous phantom and validation of complex IMRT/VMAT paradigms using gamma analysis of calculated and measured dose maps in a 2D-Array. RESULTS: Dose calculation with the GoldMC model resulted in a confidence level of 3% for point measurements in water tank and heterogeneous phantom for measurements performed in all three linacs. The same confidence level resulted for GoldCC model. Dose maps presented an agreement for all models on par to each other with γ criteria 2%/2mm. CONCLUSIONS: The GoldMC model showed a good agreement with measured data and is determined to be accurate for clinical use for all three linacs in this study.

Radiomics classifier to quantify automatic segmentation quality of cardiac sub-structures for radiotherapy treatment planning.

PURPOSE: A radiomics features classifier was implemented to evaluate segmentation quality of heart structures. A robust feature set sensitive to incorrect contouring would provide an ideal quantitative index to drive autocontouring optimization. METHODS: Twenty-five cardiac sub-structures were contoured as regions of interest in 36 CTs. Radiomic features were extracted from manually-contoured (MC) and Hierarchical-Clustering automatic-contouring (AC) structures. A robust feature-set was identified from correctly contoured CT datasets. Features variation was analyzed over a MC/AC dataset. A supervised-learning approach was used to train an Artificial-Intelligence (AI) classifier; incorrect contouring cases were generated from the gold-standard MC datasets with translations, expansions and contractions. ROC curves and confusion matrices were used to evaluate the AI-classifier performance. RESULTS: Twenty radiomics features, were found to be robust across structures, showing a good/excellent intra-class correlation coefficient (ICC) index comparing MC/AC. A significant correlation was obtained with quantitative indexes (Dice-Index, Hausdorff-distance). The trained AI-classifier detected correct contours (CC) and not correct contours (NCC) with an accuracy of 82.6% and AUC of 0.91. True positive rate (TPR) was 85.1% and 81.3% for CC and NCC. Detection of NCC at this point of the development still depended strongly on degree of contouring imperfection. CONCLUSIONS: A set of radiomics features, robust on "gold-standard" contour and sensitive to incorrect contouring was identified and implemented in an AI-workflow to quantify segmentation accuracy. This workflow permits an automatic assessment of segmentation quality and may accelerate expansion of an existing autocontouring atlas database as well as improve dosimetric analyses of large treatment plan databases.

Computed Tomography to Cone Beam Computed Tomography Deformable Image Registration for Contour Propagation Using Head and Neck, Patient-Based Computational Phantoms: A Multicenter Study.

PURPOSE: To investigate the performance of various algorithms for deformable image registration (DIR) for propagating regions of interest (ROIs) using multiple commercial platforms, from computed tomography to cone beam computed tomography (CBCT) and megavoltage computed tomography. METHODS AND MATERIALS: Fourteen institutions participated in the study using 5 commercial platforms: RayStation (RaySearch Laboratories, Stockholm, Sweden), MIM (Cleveland, OH), VelocityAI and SmartAdapt (Varian Medical Systems, Palo Alto, CA), and ABAS (Elekta AB, Stockholm, Sweden). Algorithms were tested on synthetic images generated with the ImSimQA (Oncology Systems Limited, Shrewsbury, UK) package by applying 2 specific deformation vector fields (DVF) to real head and neck patient datasets. On-board images from 3 systems were used: megavoltage computed tomography from Tomotherapy and 2 kinds of CBCT from a clinical linear accelerator. Image quality of the system was evaluated. The algorithms' accuracy was assessed by comparing the DIR-mapped ROIs returned by each center with those of the reference, using the Dice similarity coefficient and mean distance to conformity metrics. Statistical inference on the validation results was carried out to identify the prognostic factors of DIR performance. RESULTS: Analyzing 840 DIR-mapped ROIs returned by the centers, it was demonstrated that DVF intensity and image quality were significant prognostic factors of DIR performance. The accuracy of the propagated contours was generally high, and acceptable DIR performance can be obtained with lower-dose CBCT image protocols. CONCLUSIONS: The performance of the systems proved to be image quality specific, depending on the DVF type and only partially on the platforms. All systems proved to be robust against image artifacts and noise, except the demon-based software.

Hierarchical clustering applied to automatic atlas based segmentation of 25 cardiac sub-structures.

PURPOSE: Segmentation of cardiac sub-structures for dosimetric analyses is usually performed manually in time-consuming procedure. Automatic segmentation may facilitate large-scale retrospective analysis and adaptive radiotherapy. Various approaches, among them Hierarchical Clustering, were applied to improve performance of atlas-based segmentation (ABS). METHODS: Training dataset of ABS consisted of 36 manually contoured CT-scans. Twenty-five cardiac sub-structures were contoured as regions of interest (ROIs). Five auto-segmentation methods were compared: simultaneous automatic contouring of all 25 ROIs (Method-1); automatic contouring of all 25 ROIs using lungs as anatomical barriers (Method-2); automatic contouring of a single ROI for each contouring cycle (Method-3); hierarchical cluster-based automatic contouring (Method-4); simultaneous truth and performance level estimation (STAPLE). Results were evaluated on 10 patients. Dice similarity coefficient (DSC), average Hausdorff distance (AHD), volume comparison and physician score were used as validation metrics. RESULTS: Atlas performance improved increasing number of atlases. Among the five ABS methods, Hierarchical Clustering workflow showed a significant improvement maintaining a clinically acceptable time for contouring. Physician scoring was acceptable for 70% of the ROI automatically contoured. Inter-observer evaluation showed that contours obtained by Hierarchical Clustering method are statistically comparable with them obtained by a second, independent, expert contourer considering DSC. Considering AHD, distance from the gold standard is lower for ROIs segmented by ABS. CONCLUSIONS: Hierarchical clustering resulted in best ABS results for the primarily investigated platforms and compared favorably to a second benchmark system. Auto-contouring of smaller structures, being in range of variation between manual contourers, may be ideal for large-scale retrospective dosimetric analysis.

Evaluation of the effectiveness of novel single-intervention adaptive radiotherapy strategies based on daily dose accumulation.

Parotid gland (PG) shrinkage and neck volume reduction during radiotherapy of head and neck (H&N) cancer patients is a clinical issue that has prompted interest in adaptive radiotherapy (ART). This study focuses on the difference between planned dose and delivered dose and the possible effects of an efficient replanning strategy during the course of treatment. Six patients with H&N cancer treated by tomotherapy were retrospectively enrolled. Thirty daily dose distributions (DMVCT) were calculated on pretreatment megavoltage computed tomography (MVCT) scans. Deformable Image Registration which matched daily MVCT with treatment planning kilovoltage computed tomography was performed. Using the resulting deformation vector field, all daily DMVCT were deformed to the planning kilovoltage computed tomography and resulting doses were accumulated voxel per voxel. Cumulative DMVCT was compared to planned dose distribution performing γ-analysis (2 mm, 2% of 2.2 Gy). Two single-intervention ART strategies were executed on the 18th fraction whose previous data had suggested to be a suitable timepoint for a single replanning intervention: (1) replanning on the original target and deformed organ at risks (OARs) (a "safer" approach regarding tumor coverage) and (2) replanning on both deformed target and deformed OARs. DMVCT showed differences between planned and delivered doses (3D-γ 2mm/2%-passing rate = 85 ± 1%, p < 0.001). Voxel by voxel dose accumulation showed an increase in average dose of warped PG of 3.0 Gy ± 3.3 Gy. With ART the average dose of warped PG decreased by 3.2 Gy ± 1.7 Gy in comparison to delivered dose without replanning when both target and OARs were deformed. Average dose of warped PG decreased by 2.0 Gy ± 1.4 Gy when only OARs were deformed. Anatomical variations lead to increased doses to PGs. Efficient single-intervention ART-strategies with replanning on the 18th MVCT result a reduced PG dose. A strategy with deformation of both target and OAR resulted in the lowest PG dose, while formally maintaining PTV coverage. Deformation of only OAR nevertheless reduces PG dose and has less uncertainties regarding PTV coverage.

Expert system classifier for adaptive radiation therapy in prostate cancer.

A classifier-based expert system was developed to compare delivered and planned radiation therapy in prostate cancer patients. Its aim is to automatically identify patients that can benefit from an adaptive treatment strategy. The study predominantly addresses dosimetric uncertainties and critical issues caused by motion of hollow organs. 1200 MVCT images of 38 prostate adenocarcinoma cases were analyzed. An automatic daily re-contouring of structures (i.e. rectum, bladder and femoral heads), rigid/deformable registration and dose warping was carried out to simulate dose and volume variations during therapy. Support vector machine, K-means clustering algorithms and similarity index analysis were used to create an unsupervised predictive tool to detect incorrect setup and/or morphological changes as a consequence of inadequate patient preparation due to stochastic physiological changes, supporting clinical decision-making. After training on a dataset that was considered sufficiently dosimetrically stable, the system identified two equally sized macro clusters with distinctly different volumetric and dosimetric baseline properties and defined thresholds for these two clusters. Application to the test cohort resulted in 25% of the patients located outside the two macro clusters thresholds and which were therefore suspected to be dosimetrically unstable. In these patients, over the treatment course, mean volumetric changes of 30 and 40% for rectum and bladder were detected which possibly represents values justifying adjustment of patient preparation, frequent re-planning or a plan-of-the-day strategy. Based on our research, by combining daily IGRT images with rigid/deformable registration and dose warping, it is possible to apply a machine learning approach to the clinical setting obtaining useful information for a decision regarding an individualized adaptive strategy. Especially for treatments influenced by the movement of hollow organs, this could reduce inadequate treatments and possibly reduce toxicity, thereby increasing overall RT efficacy.

SIS epidemiological model for adaptive RT: Forecasting the parotid glands shrinkage during tomotherapy treatment.

PURPOSE: A susceptible-infected-susceptible (SIS) epidemic model was applied to radiation therapy (RT) treatments to predict morphological variations in head and neck (H&N) anatomy. METHODS: 360 daily MVCT images of 12 H&N patients treated by tomotherapy were analyzed in this retrospective study. Deformable image registration (DIR) algorithms, mesh grids, and structure recontouring, implemented in the RayStation treatment planning system (TPS), were applied to assess the daily organ warping. The parotid's warping was evaluated using the epidemiological approach considering each vertex as a single subject and its deformed vector field (DVF) as an infection. Dedicated IronPython scripts were developed to export daily coordinates and displacements of the region of interest (ROI) from the TPS. matlab tools were implemented to simulate the SIS modeling. Finally, the fully trained model was applied to a new patient. RESULTS: A QUASAR phantom was used to validate the model. The patients' validation was obtained setting 0.4 cm of vertex displacement as threshold and splitting susceptible (S) and infectious (I) cases. The correlation between the epidemiological model and the parotids' trend for further optimization of alpha and beta was carried out by Euclidean and dynamic time warping (DTW) distances. The best fit with experimental conditions across all patients (Euclidean distance of 4.09 ± 1.12 and DTW distance of 2.39 ± 0.66) was obtained setting the contact rate at 7.55 ± 0.69 and the recovery rate at 2.45 ± 0.26; birth rate was disregarded in this constant population. CONCLUSIONS: Combining an epidemiological model with adaptive RT (ART), the authors' novel approach could support image-guided radiation therapy (IGRT) to validate daily setup and to forecast anatomical variations. The SIS-ART model developed could support clinical decisions in order to optimize timing of replanning achieving personalized treatments.

Radiosurgery Using Tomotherapy for Patients with Brain Oligo-metastasis: A Retrospective Analysis on Feasibility and Tolerance.

AIM: Aim of the study was to evaluate feasibility and toxicities of exclusive radiosurgery using tomotherapy in patients with brain oligo-metastases. PATIENTS AND METHODS: Between 2008 and 2013 68 patients underwent stereotactic radiosurgery (SRS). Mean patient age was 63 years. Brain was the only site involved in 32 patients, while 36 had extracranial disease. Pre-SRS MRI 56 patients had sovratentorial lesions, 10 subtentorial and 2 patients had both. Fifty-two patients had 1 brain lesion, 11 had 2, and 5 patients had three. All patients underwent SRS using Tomotherapy. The median delivered dose was 18 Gy. RESULTS: After a mean follow-up of 13 months, 14 patients were alive, while 54 patients had died. Two patients had complete response, 32 had partial response, 21 stable disease and 13 disease progression. Overall response rate was 80.9%. One- and two-year overall survival were 41,2% and 24,7%, while local control 61.5% and 37.7%. Toxicity was acceptable. CONCLUSION: SRS using tomotherapy has been proven feasible as non-invasive exclusive treatment for oligometastatic patients with good prognostic score.

A support vector machine tool for adaptive tomotherapy treatments: Prediction of head and neck patients criticalities.

PURPOSE: Adaptive radiation therapy (ART) is an advanced field of radiation oncology. Image-guided radiation therapy (IGRT) methods can support daily setup and assess anatomical variations during therapy, which could prevent incorrect dose distribution and unexpected toxicities. A re-planning to correct these anatomical variations should be done daily/weekly, but to be applicable to a large number of patients, still require time consumption and resources. Using unsupervised machine learning on retrospective data, we have developed a predictive network, to identify patients that would benefit of a re-planning. METHODS: 1200 MVCT of 40 head and neck (H&N) cases were re-contoured, automatically, using deformable hybrid registration and structures mapping. Deformable algorithm and MATLAB(®) homemade machine learning process, developed, allow prediction of criticalities for Tomotherapy treatments. RESULTS: Using retrospective analysis of H&N treatments, we have investigated and predicted tumor shrinkage and organ at risk (OAR) deformations. Support vector machine (SVM) and cluster analysis have identified cases or treatment sessions with potential criticalities, based on dose and volume discrepancies between fractions. During 1st weeks of treatment, 84% of patients shown an output comparable to average standard radiation treatment behavior. Starting from the 4th week, significant morpho-dosimetric changes affect 77% of patients, suggesting need for re-planning. The comparison of treatment delivered and ART simulation was carried out with receiver operating characteristic (ROC) curves, showing monotonous increase of ROC area. CONCLUSIONS: Warping methods, supported by daily image analysis and predictive tools, can improve personalization and monitoring of each treatment, thereby minimizing anatomic and dosimetric divergences from initial constraints.

[2,8-dihydroxyadenine urolithiasis: case report and literature review]. / Calcolosi di 2,8-diidrossiadenina. Descrizione di un caso clinico e revisione della letteratura.

INTRODUCTION: 2,8-Dihydroxyadenine (DHA) urolithiasis is a rare type of urinary stone disease secondary to deficiency of adenine phosphoribosyltransferase (APRT) activity, a rare, inherited autosomal recessive disease with an incidental rate from 0.4 to 1.2%. The prevalence is higher among Japanese than other ethnic groups. APRT normally catalyzes the conversion of adenine to adenosine monophosphate and its deficiency results in 2,8-dihydroxyadenine (2,8-DHA) accumulation. This compound is extremely insoluble and its crystallization can lead to stone formation and renal failure. We report the case of 2,8-dihydroxyadenine (DHA) urolithiasis in a 52-year-old male patient. MATERIAL AND METHODS: In December 2008 a 52-year-old Caucasian man was admitted to our hospital with sudden pain in the left lumbar region. Abdominal X-ray did not show any radiopaque urinary stone. I.V. pielography showed a radiolucent left lumbar ureteral (0.6 mm) and renal (1.5 cm) stone. After therapy with tamsulosin, the ureteral stone was excreted. Successful ESWL treatment was performed for renal stone. He presented a clinical history of several episodes of bilateral renal colic and two prior ESWL treatment for radiolucent stones. Chemolitholysis was never successful. RESULTS. Stone analysis by infrared spectroscopy and microscopic examination of urine reveal typical 2,8-DHA crystals. APRT deficiency was detected in the hemolysate of erythrocyte. Partial deficiency of APRT in the patient's relatives showed heterozygosity of the enzyme defect. Allopurinol therapy successfully prevented further stone formation. 20 months later the patient remains stone free. CONCLUSION: Two types of deficit are commonly distinguished, depending on the level of residual APRT activity. Type I is complete enzyme deficiency. Type II shows residual activity in cell lysates, but enzyme activity is not demonstrable in intact cells. About 78% of the Japanese patients belong to type II. The diagnosis of the disease is based on stone analysis by infrared spectroscopy or microscopic examination of urine, which may reveal typical 2,8-DHA crystals. Molecular approach can identify mutations, which are responsible of this inherited disease. Excessive water intake, restriction of foods with high adenine contents and administration of allopurinol are useful treatments. APRT deficiency is a rare disease but we can consider this pathology in case of recurrent radiolucent stones after chemolitolysis.

[Fibromyxoid sarcoma of the kidney. A case report]. / Sarcoma fibromixoide del rene.

Low grade fibromyxoid sarcoma is an uncommon soft tissue tumor. We present the case of a 83-year-old female who developed large mass in the right kidney. A nephrectomy was performed. The tumor measured 18,5x17,5x11,5 cm and on pathology evaluation was diagnosed as low grade fibromyxoid sarcoma. Currently, the patient is doing well without evidence of local recurrence and distant metastasis. Low grade fibromyxoid sarcoma of the Kidney is a very rare tumor. The metastasizing potential is high. Sometimes long interval between tumor presentation and metastasis is observed. The treatment of choice is surgery. The role of radiotherapy and chemotherapy is uncertain.

Original and reviewed nuclear grading according to the Fuhrman system: a multivariate analysis of 388 patients with conventional renal cell carcinoma.

BACKGROUND: The objective of the current study was to evaluate the reproducibility of the Fuhrman nuclear grading system as well as its independent predictive value in a series of patients with conventional renal cell carcinoma (RCC). METHODS: The authors selected 388 patients who had undergone surgical treatment for conventional RCC between 1986 and 2000. Pathology slides from the selected patients were reviewed by a single pathologist, who reassigned a Fuhrman nuclear grade and assessed the presence of tumor necrosis. The pathologist was blinded to both the original pathologic diagnosis and follow-up data. The kappa statistic was used to evaluate concordance between original and reviewed nuclear grades. The log-rank test was used for univariate analyses, and a Cox proportional hazards model was used for multivariate analyses. RESULTS: The original Fuhrman nuclear grade was Grade 1 (G1) in 111 patients (28.6%), G2 in 141 patients (36.3%), G3 in 108 patients (27.8%), and G4 in 28 patients (7.3%). After pathology slide review, nuclear grades were reassigned as follows: G1 in 49 patients (12.6%), G2 in 138 patients (35.6%), G3 in 150 patients (38.7%), and G4 in 51 patients (13.1%). The grade of concordance was moderate (kappa=0.44; P <0.001). Univariate analyses identified three separate prognostic categories defined by nuclear grade (G1 and G2 vs. G3 vs. G4). Both the original and the reviewed Fuhrman nuclear grading systems were capable of independently predicting disease-specific survival in patients with conventional RCC. CONCLUSIONS: The interobserver reproducibility of Fuhrman nuclear grading was moderate. The substantial overlap in survival curves for G1 and G2 tumors provided an opportunity to cluster those categories, and the resulting three-tiered nuclear grading system was an independent predictor of cause-specific survival in patients with conventional RCC. Other independent predictors of survival included pathologic stage and tumor necrosis status.

Incidental detection beyond pathological factors as prognostic predictor of renal cell carcinoma.

PURPOSE: To evaluate the prognostic significance of different detection modalities of renal cell carcinoma (RCC) in a large cohort of patients who had been previously submitted to surgery in two teaching hospitals in Italy. MATERIALS AND METHODS: We reviewed the clinical records of 1446 patients who had been submitted to surgical treatment for RCC at the Departments of Urology of Padua (n=747) and Verona (n=699) from 1976 to 2000. Patients were classified into two groups according to the detection mode: symptomatic and incidental. The cancer-specific survival probability was estimated according to the Kaplan-Meier method. In order to compare the survival curves the log rank test was used. The predictive independent value of the variables was examined using the Cox proportional hazards model. RESULTS: Six hundred and thirty patients (43.6%) were treated for incidental RCC and 816 (56.4%) for symptomatic RCC. In the incidental group, the size (p<0.001), the pathological stage (p<0.001) and the nuclear grading (p<0.001) of tumors were lower than those causing symptoms. The 5-year and 10-year cancer-specific survival probability were 84% and 75% in the incidental group, and 66% and 54.5% in the symptomatic group (p<0.0001), respectively. At a multivariate analysis, the mode of detection was an independent predictive variable (H.R. 1.559), as well as pathological stage (H.R. 1.809), nuclear grading (H.R. 1.411), size

Role of uCyt+ in the detection and surveillance of urothelial carcinoma.

OBJECTIVES: To test the clinical value and role of uCyt+ as a noninvasive tool for the detection and surveillance of urothelial carcinoma. METHODS: Included in this prospective study were 235 patients (mean age 71.5 years, range 32 to 86). Of these, 98 patients had signs and symptoms suggestive of bladder cancer and 137 patients were being followed up after complete transurethral resection of superficial urothelial cancer (UC). All patients underwent urinary cytology and the uCyt+ test performed on ThinPrep (thin layer). All underwent subsequent cystoscopy and evaluation of any suspicious lesion by biopsy. RESULTS: A total of 102 patients had histologically proven UC. In the group of patients with signs and symptoms suspicious of UC, the sensitivity of cytology increased from 5% for G1 to 84.6% for G3 tumors; for uCyt+, it was 85% for G1, 100% for G2, and 92.3% for G3 tumors. Combining cytology and uCyt+, the sensitivity was 85% for G1 and 100% for G2 and G3. In the group of follow-up patients, the sensitivity of cytology increased from 4.3% for G1 to 94.4% for G3 tumors; for uCyt+, it was 78.2% for G1, 70% for G2, and 94.4% for G3 tumors. Combining both tests, the sensitivity was 78.2% for G1, 90% for G2, and 100% for G3. CONCLUSIONS: The uCyt+ is a valid test in the detection of UC of all grades and stages. It improves the sensitivity of cytology in low-grade tumors. The two tests combined may be a highly sensitive method to detect UC early in detection and surveillance.

Local treatment of penile squamous cell carcinoma.

Treatment of primary tumour represents one of the main issues in the management of squamous cell carcinoma of the penis. Radical surgery assures the best results in terms of oncological radicality but causes important anatomical and functional limitations and a significant quality of life compromise. It is possible to suggest a penile-sparing treatment in the presence of small size and low stage tumours. The local recurrence rates seem higher than radical surgery and the functional and aesthetic results are not excellent in all cases. Moreover, radiotherapy seems to have a negligible percentage of local complications.

Management of clinical stage I testicular pure seminoma. Report on 42 patients and review of the literature.

INTRODUCTION: Testis cancer is the most common tumor detected in men aged from 20 to 35 years accounting for 1-2%. About 20-30% of patients presenting with clinical stage I pure seminoma of the testis, which accounts for 45-50% of all germ cell tumors, present with occult metastases in the retroperitoneal lymph nodes. Currently, treatment options for clinical stage I seminoma include adjuvant radiotherapy (RT) as well as surveillance and adjuvant single agent chemotherapy. Herein, we review our experience in the management of 42 patients with clinical stage I pure seminoma of the testis and review the literature concerning this topic. MATERIALS AND METHODS: Between January 1977 and December 2000, of 56 patients with pure seminoma of the testis 42 (75%) were assessed as clinical stage I disease. Adjuvant RT was performed in 41 patients and surveillance in 1. Radiations fields included the para-aortic and ipsilateral pelvic lymph nodes. A radiation dose of 25 Gy in 20 daily fractions was given. All patients were followed up. RESULTS: Average age was 41.2 years (range 24-67). Mean follow-up was 85.3 months (range 12-279). Histopathology assessed classic seminoma in 41 cases (98%) and spermatocytic seminoma in 1 (2%). Small vessel invasion was detected in 8 cases (19%). Overall relapse rate was 4.7%. Overall survival rate resulted 97%. CONCLUSIONS: Adjuvant radiotherapy (RT) is a safe standard of care in controlling microscopic retroperitoneal disease in patients with clinical stage I seminoma. About 3 to 5% of patients undergo relapses, mostly after the first 18 months after orchiectomy. Overall cause-specific survival rates range between 96% to 100%. An alternative optional treatment for compliant patients presenting with low risk factors for relapse is surveillance with recurrences rates ranging between 15% to 20%. Surveillance avoids unnecessary treatment in about 80% of patients, thus it could be offered as a safe alternative option to adjuvant RT since imaging detects relapses at their early stages. Adjuvant chemotherapy with 1 or 2 courses of single-agent carboplatin is being investigated as an alternative adjuvant treatment to RT or surveillance in patients with moderate to high risk factors for relapse. The treatment is well tolerated and recurrence rate is 1%.

Management of testicular seminoma advanced disease. Report on 14 cases and review of the literature.

INTRODUCTION: About 25% of testicular seminomas present with advanced clinical stage disease. The retroperitoneal lymph nodes are more likely to be involved (20%) than distant organs (5%). Herein we review our experience in the management of 14 patients with clinical stage II pure seminoma of the testis and review the literature concerning this subject. MATERIALS AND METHODS: Between January 1977 and December 2000, of 56 patients with pure seminoma of the testis 14 (25%) were assessed as clinical stage II disease. RT was performed for clinical substage IIA-IIB and chemotherapy in for IIC disease. All patients were closely followed up. RESULTS: Average age was 39.3 years (range 23-47). Mean follow-up was 88.6 months (range 28-232). Clinical stage IIA-IIB was detected in 12 patients (86%) and IIC in 2 (14%). Relapse did not occur in any patient. At the last follow-up evaluation, all patients were alive and disease-free. CONCLUSIONS: Radiation therapy is the standard of care in managing seminoma small bulk retroperitoneal disease including substages IIA and IIB. Overall toxicity of RT is mild and treatment is well tolerated. After RT, about 20% of patients may undergo relapses. Chemotherapy is the choice treatment for advanced seminoma presenting with clinical stage IIC-III disease; recently, it has also been advocated for stage IIB when presenting with multiple small lymph nodes. Carboplatin and cisplatin are the most effective agents with complete response rates of 89-91%. Patients developing progressive disease after first-line chemotherapy undergo combined salvage chemotherapy with cisplatin, ifosfamide and vinblastine with complete response rate of 83%. Patients presenting salvage chemotherapy failure are treated with high-dose chemotherapy associated with autologous bone marrow transplantation. Residual retroperitoneal masses after chemotherapy for advanced seminoma may be assessed by imaging as poorly or well defined. Surveillance is indicated for residual masses smaller than 3 cm as well as for poorly defined masses equal or greater than 3 cm. Well defined masses equal or larger than 3 cm are treated with surgery or RT. Ongoing clinical trials for testicular germ cell metastatic disease are focused on reducing toxicity without compromising efficacy as well as exploring new salvage strategies and improving the prospect of cures and survival rates.

Prognostic factors in patients with renal cell carcinoma: retrospective analysis of 675 cases.

OBJECTIVES: To identify independent predictors of cause-specific survival in patients affected by renal cell carcinoma (RCC). MATERIAL AND METHODS: We evaluated retrospectively 675 patients who underwent in our department from 1976 to 1999 radical nephrectomy for RCC. Pathological stage of the primary tumor (TNM, 1997) was pT1 in 326 cases (48%), pT2 in 133 (20%), pT3a in 66 (10%), pT3b in 138 (20%) and pT4 in 12 (2%). According to TNM classification (Union International Contre le Cancer (UICC), 1997) the pathological stage was I in 303 cases (45%), II in 119 (18%), III in 150 (22%) and IV in 103 (15%). Histological grading was assigned according to Fuhrman's classification in only 333 cases: G1 in 25%, G2 in 35%, G3 in 33% and G4 in 7%. RESULTS: Cause-specific survival was 77% at 5 years, 69% at 10 years, 64% at 15 years and 57% at 20 years. Five and 10 year cause-specific survival was, respectively 91.4 and 88.5% in pT1 tumors, 84.8 and 72.7% in pT2, 57.4 and 35.6% in pT3a, 47.2 and 33.6% in pT3b-c, and 29.6% in pT4 (P < 0.0001). In relation to the pathological stage according to TNM classification, 5 and 10 year cause-specific survival was, respectively 94 and 91.6% in stage I tumors, 89.7 and 78% in stage II, 63.4 and 46.4% in stage III and 28 and 16.3% in stage IV (P < 0.0001). In relation to the nuclear grade of the primary tumor 5 and 10 year cause-specific survival was, respectively 94 and 88% in G1 tumors, 86 and 75% in G2, 59 and 40% in G3 and 31% in G4 (P < 0.0001). At multivariate analysis pathological stage of the primary tumor, lymph nodes involvement, presence of distant metastases at diagnosis and nuclear grading resulted all independent predictors of cause-specific survival in patients with RCC. CONCLUSION: Pathological stage of primary tumors, lymph nodes involvement, presence of distant metastases at diagnosis and nuclear grading according to Fuhrman resulted all independent predictors of cause-specific mortality in patients with RCC.

Predictive pathological factors of lymph nodes involvement in the squamous cell carcinoma of the penis.

OBJECTIVES: To evaluate the predictive role of primary tumor histopathological features in predicting inguinal lymph nodes involvement in patients with penile squamous cell carcinoma. MATERIAL AND METHODS: We retrospectively analysed pathological records from 30 consecutive patients who underwent penectomy for invasive squamous cell carcinoma of the penis. All histological specimens were reviewed by the same pathologist. We considered the following histological parameters: histological grading, growth pattern, deph invasion, tumour thickness, nuclear grading, poorly differentiated cancer rate, vascular and lymphatic embolization, eosinophilic and mononuclear infiltration and pathological stage. RESULTS: Lymph nodes involvement occurred in 5 patients who underwent 'early' lymphadenectomy and in other 4 ones during oncological surveillance. Lymph nodes metastasis resulted significantly correlated with histological grading (p = 0.005), lymphatic (p = 0.005) and venous (p = 0.02) embolization, corpora cavernosa (p = 0.03) and urethra (p = 0.03) infiltration. Histological grading and lymphatic embolization were independent predictive variables of lymph nodes involvement (p = 0.02). CONCLUSIONS: The histological grading and lymphatic embolization have to be considered as important parameters to select patients with penile squamous cell carcinoma to undergo an 'early' lymphadenectomy.