Stereotactic ablative radiotherapy in castration-resistant prostate cancer patients with oligoprogression during androgen receptor-targeted therapy.

OBJECTIVES: To report outcomes of stereotactic body radiotherapy (SBRT) in metastatic castration-resistant prostate cancer (mCRPC) patients with oligoprogression (≤ 5 metastases) during first-line treatment with androgen receptor-targeted therapy (ARTT). PATIENTS AND METHODS: Retrospective multi-institutional analysis of mCRPC patients treated with SBRT to oligoprogressive lesions during ARTT. End-points were time to next-line systemic treatment (NEST), radiological progression-free survival (r-PFS) and overall survival (OS). Toxicity was registered according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Survival analysis was performed using the Kaplan-Meier method, univariate and multivariate analysis (MVA) were performed. RESULTS: Data from 34 patients were analyzed. Median NEST-free survival, r-PFS, and OS were 16.97, 13.47, and 38.3 months, respectively. At MVA, factors associated with worse NEST-free survival and r-PFS were polymetastatic burden at diagnosis of metastatic hormone-sensitive disease (hazard ratio [HR] 3.66, p = 0.009; HR 3.03, p = 0.034), PSA ≤ 7 ng/ml at mCRPC diagnosis (HR 0.23, p = 0.017; HR 0.19, p = 0.006) and PSADT ≤ 3 months at mCRPC diagnosis (HR 3.39, p = 0.026; HR 2.79, p = 0.037). Polymetastatic state at mHSPC diagnosis was associated with a decreased OS (HR 4.68, p = 0.029). No patient developed acute or late grade ≥ 2 toxicity. CONCLUSION: Our results suggest that SBRT in oligoprogressive mCPRC is safe, effective and seems to prolong the efficacy of the ongoing systemic treatment positively affecting disease progression. Prospective trials are needed.

Macroscopic locoregional relapse from prostate cancer: which role for salvage radiotherapy?

INTRODUCTION: Salvage radiotherapy (SRT) after radical prostatectomy for prostate cancer (PCa) is recommended as soon as PSA rises above 0.20 ng/ml, but many patients (pts) still experience local macroscopic relapse. The aim of this multicentric retrospective analysis was to evaluate the role of SRT in pts with macroscopic relapse. MATERIALS AND METHODS: From 2001 to 2016, 105 consecutive pts with macroscopic PCa relapse underwent SRT ± androgen deprivation therapy (ADT). Mean age was 72 years. At time of relapse, 29 pts had a PSA value < 1.0 ng/mL, 50 from 1.1 to 5, and 25 pts > 5. Before SRT, 23 pts had undergone 18F-choline PET and 15 pts pelvic MRI. Ninety-four pts had prostatic bed relapse only, and four nodal involvement. Fifty-one pts were previously submitted to first-line ADT, while 6 pts received ≥ 2 lines. RESULTS: At a median follow-up of 52 months, 89 pts were alive, while 16 were dead. Total RT dose to macroscopic lesions was > 70 Gy in 58 pts, 66-70 Gy in 43, and < 66 Gy in 4 pts. In 72 pts, target volume encompassed only the prostatic bed with sequential boost to macroscopic site; 33 pts received prophylactic pelvic RT. Ten-year overall survival was 76.1%, while distant metastasis-free survival was 73.3%. No grade 4-5 toxicities were found. CONCLUSIONS: SRT ± ADT for macroscopic relapse showed a favorable oncological outcome supporting its important role in this scenario. Data from this series suggest that SRT may either postpone ADT or improve results over ADT alone in appropriately selected pts.

Hypofractionated stereotactic radiotherapy for intracranial meningiomas: preliminary results of a feasible trial.

AIM: Fractionated stereotactic radiotherapy is an alternative to radiosurgery or conformal radiotherapy when meningiomas are surgically inaccessible, incompletely removed, or recurrent. The authors report preliminary results of a feasible trial on hypofractionated stereotactic radiotherapy (hFSRT) in patients (pts) with intracranial meningiomas. METHODS: From August 2003 to May 2007, 35 consecutive pts with a median age of 59 years (range, 23-86) underwent hFSRT for intracranial meningiomas. Male/female ratio was 9/26, median Karnofsky performance status was 90 (range, 60-100). In 14 lesions (40%) diagnosis was based upon clinical and radiological data. After surgery or biopsy, 19 pts had histologically proven World Health Organization grade I and 2 pts grade II meningiomas. The median treatment volume was 23 cc (range, 4-58 cc). Before hFSRT, 26 (74%) pts had neurologic symptoms. Nineteen (54%) pts received 42 Gy and 16 (46%) 45 Gy of total dose, 3 Gy/fraction, 5 fractions/week. RESULTS: The median follow-up was 29 months (range, 10-51) and 22 (63%) pts had a follow-up 24 months. Treatment was well tolerated and we did not observe clinically significant acute and late toxicity. At instrumental control, 32 (91%) lesions remained stable, 2 (6%) decreased and 1 (3%) progressed in size. Median duration of local control was 24 months (range, 4-47), and median progression free survival 23 months (range, 4-47). Clinical improvement of pre-existing neurological symptoms was observed in 84% of cases. CONCLUSIONS: These preliminary data suggest that hFSRT is a safe and effective treatment modality for intracranial meningiomas.

Benign and malignant breast lesions: efficacy of real time contrast-enhanced ultrasound vs. magnetic resonance imaging.

PURPOSE: To assess the efficacy of low mechanical index (MI) real time grey scale contrast-enhanced US (CEUS) in the differentiation of breast lesions in comparison to Magnetic Resonance Imaging (MRI). MATERIALS AND METHODS: 50 lesions previously detected at mammography or conventional US were evaluated by means of CEUS and MRI. Contrast-enhanced examinations were performed with a dedicated equipment (Esatune, Esaote, Genoa, Italy), before and after injection of 4.8 ml of Sonovue (Bracco, Milan, Italy). MRI was conducted with a 1.5 T equipment (Siemens Vision Plus, Erlangen, Germany) with bilateral dedicated superficial coil, on T2w STIR and 3D Flash T1w before and 1, 2, 3, 4, 5 minutes after the administration of contrast agent (Gd-DTPA, 1.5 ml/kg). Wash-in and wash-out curves were assessed for both procedures. A specific sonographic quantification software (Qontrast, Bracco, Milan, Italy), based on pixel by pixel signal intensity over time, was used to obtain contrast-enhanced sonographic perfusion maps for each lesion. Mc Nemar test was then calculated. RESULTS: 24 invasive ductal carcinomas, 18 fibroadenomas, 4 fibro-cystic dysplasias, 1 mucinous carcinoma, 1 invasive ducto-lobular carcinoma, 1 intraductal florid papillomatosis and 1 phylloides tumour were diagnosed. Contrast-enhanced sonographic patterns correlated well with those provided by MRI. Sensitivity, specificity, and accuracy of US were: 69.2 %, 66.7 %, and 68 %, respectively. According to the different contrast enhancement patterns and the resulting perfusion maps, all the malignant lesions and 9 out of 12 benign lesions were correctly diagnosed, thus resulting in 87.5 % of specificity and 100 % of sensitivity. Regarding the specificity, there is no difference between US and CEUS with McNemar (p = 0.18). Regarding sensitivity, the difference between contrast-enhanced US and US is significant as calculated with McNemar test (p = 0.013). The three lesions which were incorrectly classified as malignant were two hypervascularised fibroadenomas in young women and a phylloides tumour. CONCLUSION: CEUS seems to be a reliable method to differentiate breast lesions, since it provides typical enhancement patterns. Contrast sonographic perfusion curves correlate well with MRI wash in--wash out curves.

Esophagogram and CT vs endoscopic and surgical specimens in the diagnosis of esophageal carcinoma.

PURPOSE: Aim of our study was to assess the accuracy of diagnostic imaging in establishing site, morphology and size of the neoplasm comparing surgical specimens or endoscopic examination with esophagograms and CT in patients with esophageal cancer. CT accuracy in defining TNM staging was also evaluated. MATERIAL AND METHODS: From 1993 to 2000 we examined 39 patients with esophageal cancer: 30 males (77%) and 9 females (23%), age range 41-85 years. All patients underwent esophagogram, digestive endoscopy, and chest and abdominal CT. In 22 patients who underwent surgery, we evaluated the correlation between diagnostic imaging and surgical specimens. Patients were divided into 3 groups on the basis of discrepancy between pathological and radiological measurements: =/<1 cm (considered as no discrepancy); 1 to 3 cm; > 3 cm. RESULTS: Esophagogram identified neoplasm in 38 patients out of 39, while CT identified neoplasm in all patients. Location and morphology of the neoplasm established at endoscopy were confirmed in all patients. Lesion length measured at esophagogram corresponded to length of surgical specimens in 13 of the 22 surgically treated patients (59%). In this group there was a dominance of polypoid and stenotic tumor forms. In the remaining 9 cases there was a dominance of ulcerative tumor forms. CT measurement corresponded in 7 patients (32%) with a dominance of polypoid and stenotic tumor forms. T staging performed with CT corresponded to surgical specimens in 12 patients (54%, T3-T4). N staging correlated in 19 patients (86%). CT identified distant metastases in 6 patients (27%). DISCUSSION AND CONCLUSIONS: Our study proves a high sensitivity of esophagogram and CT in the diagnosis of esophageal carcinoma. Esophagogram presented a higher accuracy in establishing tumor length (59% of cases, as compared to CT 32%). Tumor morphology influenced the accuracy of the esophagogram, and highest accuracy was obtained in polypoid and stenotic tumors. T staging performed with CT corresponded to surgical specimens in advanced stages (T3-T4), while accuracy was poorer in smaller superficial lesions (T1-T2) due to the inability of CT to differentiate the layers of the esophageal wall. N understaging in 14% of cases did not modify surgical management. CT presented a high sensitivity in the identification of loco-regional lymph nodes and identified distant metastases in 6 patients. In conclusion, these techniques are accurate and non-invasive and their role in establishing the correct management is therefore important.

[Role of color Doppler US in the evaluation of renal transplant]. / Ruolo dell'eco color-Doppler nella diagnostica del rene trapiantato.

AIM: To assess the role of Ultrasound (US), US Color Doppler (CD) and Power Doppler (PD) in the diagnosis and in the follow-up of renal graft pathology by evaluating morphological and functional features of the vasculature and comparing these to other clinical parameters. MATERIAL AND METHODS: From January 1990 to June 2000, four hundred and thirty-six renal allograft recipients (mean age 45 years) underwent periodical US, CD and PD (mean follow-up 48 months) to evaluate morphology and perfusion of the graft. Resistive index (RI) and pulsatility index (PI) were measured in order to monitor flow variations from the renal to the arcuate arteries. PD was used mainly to study the morphology of the cortical vessels. The examinations were performed on an Esaote Biomedica AU-4/5 (Genoa, Italy) using a convex 3.5 MHz probe and a linear 7.5 MHz probe. On the basis of clinical data the patients were divided into 3 groups: A) Normal, B) Acute graft dysfunction, C) Chronic allograft nephropathy. In 87 patients (20%) percutaneous biopsy or FNAB was performed. RI and PI mean values +/-SD were calculated and compared to the other diagnostic parameters considered: serum creatinine level, US morphology, CD and PD vascularization. Finally RI and PI for each group were compared using the t -test in order to determine the statistical significance of the correlation between these indices and the patients clinical conditions. RESULTS: The 436 patients were divided as follows: Group A) 170 patients (39%); Group B) 105 patients (24%); Group C) 161 patients (37%). Urological and surgical complications were ruled out in all patients. RI and PI showed a similar trend exceeding cut-off values in Group B) and C) with highest peaks in Group B. Statistical analysis demonstrated the efficacy of this method in the differentiation between normal and pathological grafts, but there was a reduced statistical difference between the two pathological groups. Histological analysis performed on 87 patients (20%) showed good correlation with RI. DISCUSSION AND CONCLUSIONS: CD is a non-invasive diagnostic method which provides flow-metric quantitative parameters for the hemodynamic assessment of the renal transplant. These values present a certain sensitivity but are not specific of renal graft dysfunction, as there is no reliable differentiation between acute rejection and other parenchymal pathologies. During the follow-up, RI and PI have no predictive value. RI variations from renal artery to cortical vessels (hylum-cortical ratio) show a good correlation with the clinical evolution of the transplant. The evaluation of RI and PI can generally be limited to renal and interlobar arteries as arcuate sampling is necessary only when the hylum-cortical ratio shows reduction or inversion. Integration of clinical and instrumental diagnoses can reduce the number of biopsies.

[Role of color Doppler echography in the visualization of perianal fistulae with injections of physiologic solutions]. / Ruolo dell'eco color Doppler nella visualizzazione delle fistole perianali mediante iniezione di soluzione fisiologica.

PURPOSE: To prove the diagnostic value of color Doppler US in the evaluation of perianal external fistulae, using an endocavitary probe and a saline solution injection, in order to show the location of the fistulae, their extension, possible secondary tracts, residual abscesses and the relationship with adjacent tissues. MATERIAL AND METHODS: From October 1999 to December 1999, thirty-five consecutive patients (21 males and 14 females, mean age 47.5) affected with Crohn's disease were examined prospectively. These patients presented postoperative recurring external perianal fistulae. From this first group, 10 patients (6 males and 4 females, mean age 45) were selected as the external fistula was open. A biplanar transrectal 7.5 MHz probe was used for the examination. First the external opening of the fistula was cannulated with a soft plastic catheter. Then the probe, covered with a lubricated condom filled with US gel, was introduced into the anal canal (males) or the vagina (females). An initial gray-scale US study was performed. Finally the color-box was positioned on the tract, the Pulse Repetition Frequency (PRF) adjusted and the saline solution introduced. The study was completed with axial and linear scans. RESULTS: The mean examination duration was 31 minutes. Only two patients found the examination annoying because of partial anorectal stricture. The wall layers and their thickness were clearly located and distinguished. Gray-scale US showed the local anatomy in all patients. In 4 patients it depicted the primary fistula as a thin hypoecoic line (40%, three intersphinteric and one transphinteric). Color Doppler US detected the fistula in all patients (100%, seven intersphinteric and three transphinteric). Moreover it showed 2 small secondary tracts in 2 patients. No abscesses were found at the time of the examination. In the patients who underwent a second operation, surgical findings showed a good correlation (90-100%) with color Doppler findings. DISCUSSION AND CONCLUSIONS: This study demonstrated a greater diagnostic value of endosonography with color Doppler and saline solution injection as compared to conventional gray-scale endosonography in the evaluation of fistulae. Since this technique is also cost-effective and well tolerated by most patients we conclude that at present it makes an important diagnostic tool in the preoperative assessment of perianal fistulae.

European projects in radiological data bases for telemedicine and teaching.

Aim of this study is to describe the main characteristics of the European projects IAEVA II and HERMES whose principal objective is to render the already functioning computer systems more efficient. The medical environment is in continuous need of faster and better ways of communication, particularly in a radiological context, and this work therefore presents the above projects mainly from a radiological point of view.

Natural interferon-beta and tamoxifen in hormone-resistant patients with advanced breast cancer.

Tamoxifen (T) is the mainstay of hormonal treatment and is able to give high response rates in selected postmenopausal women with advanced breast cancer (ABC). Nevertheless, even in responders, invariably resistance to hormones is developed. In a previous paper we reported that in a subset of patients (pts) with metastatic breast cancer the resistance to the antiestrogen could be overcome by pretreatment with natural interferon-beta (nIFN-beta) followed by the association of nIFN-beta and T. In the present study we adopted a treatment schedule employing nIFN-beta (3 x 10(6) IU/day im three times a week) and T (60 mg/day) concurrently in 30 pts with ABC progressive to previous treatment with T (30 mg/day). We obtained a 13% response rate with a median duration of response of 8 months (range 4-16 m). All the responses occurred in pts whose disease progressed after an initial response to T. Stabilisation of disease was observed in 37%. Toxicity was mild. In our opinion the use of the combination T plus nIFN-beta in the treatment of breast cancer remains investigational and the optimal scheduling still undetermined.