Drug-induced interstitial lung disease during cancer therapies: expert opinion on diagnosis and treatment.

BACKGROUND: Drug-induced interstitial lung disease (DIILD) is a form of interstitial lung disease resulting from exposure to drugs causing inflammation and possibly interstitial fibrosis. Antineoplastic drugs are the primary cause of DIILD, accounting for 23%-51% of cases, with bleomycin, everolimus, erlotinib, trastuzumab-deruxtecan and immune checkpoint inhibitors being the most common causative agents. DIILD can be difficult to identify and manage, and there are currently no specific guidelines on the diagnosis and treatment of DIILD caused by anticancer drugs. OBJECTIVE: To develop recommendations for the diagnosis and management of DIILD in cancer patients. METHODS: Based on the published literature and their clinical expertise, a multidisciplinary group of experts in Italy developed recommendations stratified by DIILD severity, based on the Common Terminology Criteria for Adverse Events. RESULTS: The recommendations highlight the importance of multidisciplinary interaction in the diagnosis and management of DIILD. Important components of the diagnostic process are physical examination and careful patient history-taking, measurement of vital signs (particularly respiratory rate and arterial oxygen saturation), relevant laboratory tests, respiratory function testing with spirometry and diffusing capacity of the lung for carbon monoxide and computed tomography/imaging. Because the clinical and radiological signs of DIILD are often similar to those of pneumonias or interstitial lung diseases, differential diagnosis is important, including microbial and serological testing to exclude or confirm infectious causes. In most cases, management of DIILD requires the discontinuation of the antineoplastic agent and the administration of short-term steroids. Steroid tapering must be undertaken slowly to prevent reactivation of DIILD. Patients with severe and very severe (grade 3 and 4) DIILD will require hospitalisation and often need oxygen and non-invasive ventilation. Decisions about invasive ventilation should take into account the patient's cancer prognosis. CONCLUSIONS: These recommendations provide a structured step-by-step diagnostic and therapeutic approach for each grade of suspected cancer-related DIILD.

Predicting locally advanced rectal cancer response to neoadjuvant therapy with 18F-FDG PET and MRI radiomics features.

PURPOSE: Pathological complete response (pCR) following neoadjuvant chemoradiotherapy or radiotherapy in locally advanced rectal cancer (LARC) is reached in approximately 15-30% of cases, therefore it would be useful to assess if pretreatment of 18F-FDG PET/CT and/or MRI texture features can reliably predict response to neoadjuvant therapy in LARC. METHODS: Fifty-two patients were dichotomized as responder (pR+) or non-responder (pR-) according to their pathological tumor regression grade (TRG) as follows: 22 as pR+ (nine with TRG = 1, 13 with TRG = 2) and 30 as pR- (16 with TRG = 3, 13 with TRG = 4 and 1 with TRG = 5). First-order parameters and 21 second-order texture parameters derived from the Gray-Level Co-Occurrence matrix were extracted from semi-automatically segmented tumors on T2w MRI, ADC maps, and PET/CT acquisitions. The role of each texture feature in predicting pR+ was assessed with monoparametric and multiparametric models. RESULTS: In the mono-parametric approach, PET homogeneity reached the maximum AUC (0.77; sensitivity = 72.7% and specificity = 76.7%), while PET glycolytic volume and ADC dissimilarity reached the highest sensitivity (both 90.9%). In the multiparametric analysis, a logistic regression model containing six second-order texture features (five from PET and one from T2w MRI) yields the highest predictivity in distinguish between pR+ and pR- patients (AUC = 0.86; sensitivity = 86%, and specificity = 83% at the Youden index). CONCLUSIONS: If preliminary results of this study are confirmed, pretreatment PET and MRI could be useful to personalize patient treatment, e.g., avoiding toxicity of neoadjuvant therapy in patients predicted pR-.

Computer-aided diagnosis of prostate cancer using multi-parametric MRI: comparison between PUN and Tofts models.

Computer-aided diagnosis (CAD) systems are increasingly being used in clinical settings to report multi-parametric magnetic resonance imaging (mp-MRI) of the prostate. Usually, CAD systems automatically highlight cancer-suspicious regions to the radiologist, reducing reader variability and interpretation errors. Nevertheless, implementing this software requires the selection of which mp-MRI parameters can best discriminate between malignant and non-malignant regions. To exploit functional information, some parameters are derived from dynamic contrast-enhanced (DCE) acquisitions. In particular, much CAD software employs pharmacokinetic features, such as K trans and k ep, derived from the Tofts model, to estimate a likelihood map of malignancy. However, non-pharmacokinetic models can be also used to describe DCE-MRI curves, without any requirement for prior knowledge or measurement of the arterial input function, which could potentially lead to large errors in parameter estimation. In this work, we implemented an empirical function derived from the phenomenological universalities (PUN) class to fit DCE-MRI. The parameters of the PUN model are used in combination with T2-weighted and diffusion-weighted acquisitions to feed a support vector machine classifier to produce a voxel-wise malignancy likelihood map of the prostate. The results were all compared to those for a CAD system based on Tofts pharmacokinetic features to describe DCE-MRI curves, using different quality aspects of image segmentation, while also evaluating the number and size of false positive (FP) candidate regions. This study included 61 patients with 70 biopsy-proven prostate cancers (PCa). The metrics used to evaluate segmentation quality between the two CAD systems were not statistically different, although the PUN-based CAD reported a lower number of FP, with reduced size compared to the Tofts-based CAD. In conclusion, the CAD software based on PUN parameters is a feasible means with which to detect PCa, without affecting segmentation quality, and hence it could be successfully applied in clinical settings, improving the automated diagnosis process and reducing computational complexity.

Texture features on T2-weighted magnetic resonance imaging: new potential biomarkers for prostate cancer aggressiveness.

To explore contrast (C) and homogeneity (H) gray-level co-occurrence matrix texture features on T2-weighted (T2w) Magnetic Resonance (MR) images and apparent diffusion coefficient (ADC) maps for predicting prostate cancer (PCa) aggressiveness, and to compare them with traditional ADC metrics for differentiating low- from intermediate/high-grade PCas. The local Ethics Committee approved this prospective study of 93 patients (median age, 65 years), who underwent 1.5 T multiparametric endorectal MR imaging before prostatectomy. Clinically significant (volume ≥0.5 ml) peripheral tumours were outlined on histological sections, contoured on T2w and ADC images, and their pathological Gleason Score (pGS) was recorded. C, H, and traditional ADC metrics (mean, median, 10th and 25th percentile) were calculated on the largest lesion slice, and correlated with the pGS through the Spearman correlation coefficient. The area under the receiver operating characteristic curve (AUC) assessed how parameters differentiate pGS = 6 from pGS ≥ 7. The dataset included 49 clinically significant PCas with a balanced distribution of pGS. The Spearman ρ and AUC values on ADC were: -0.489, 0.823 (mean); -0.522, 0.821 (median); -0.569, 0.854 (10th percentile); -0.556, 0.854 (25th percentile); -0.386, 0.871 (C); 0.533, 0.923 (H); while on T2w they were: -0.654, 0.945 (C); 0.645, 0.962 (H). AUC of H on ADC and T2w, and C on T2w were significantly higher than that of the mean ADC (p = 0.05). H and C calculated on T2w images outperform ADC parameters in correlating with pGS and differentiating low- from intermediate/high-risk PCas, supporting the role of T2w MR imaging in assessing PCa biological aggressiveness.

A new algorithm for automatic vascular mapping of DCE-MRI of the breast: Clinical application of a potential new biomarker.

BACKGROUND AND OBJECTIVE: Vascularity evaluation on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has a potential diagnostic value, but it represents a time consuming procedure, affected by intra- and inter-observer variability. This study tests the application of a recently published method to reproducibly quantify breast vascularity, and evaluates if the vascular volume of cancer-bearing breast, calculated from automatic vascular maps (AVMs), may correlate with pathologic tumor response after neoadjuvant chemotherapy (NAC). METHODS: Twenty-four patients with unilateral locally advanced breast cancer underwent DCE-MRI before and after NAC, 8 responders and 16 non-responders. A validated algorithm, based on multiscale 3D Hessian matrix analysis, provided AVMs and allowed the calculation of vessel volume before the initiation and after the last NAC cycle for each breast. For cancer bearing breast, the difference in vascular volume before and after NAC was compared in responders and non-responders using the Wilcoxon two-sample test. A radiologist evaluated the vascularity on the subtracted images (first enhanced minus unenhanced), before and after treatment, assigning a vascular score for each breast, according to the number of vessels with length ≥30mm and maximal transverse diameter ≥2mm. The same evaluation was repeated with the support of the simultaneous visualization of the AVMs. The two evaluations were compared in terms of mean number of vessels and mean vascular score per breast, in responders and non-responders, by use of Wilcoxon two sample test. For all the analysis, the statistical significance level was set at 0.05. RESULTS: For breasts harboring the cancer, evidence of a difference in vascular volume before and after NAC for responders (median=1.71cc) and non-responders (median=0.41cc) was found (p=0.003). A significant difference was also found in the number of vessels (p=0.03) and vascular score (p=0.02) before or after NAC, according to the evaluation supported by the AVMs. CONCLUSIONS: The encouraging, although preliminary, results of this study suggest the use of AVMs as new biomarker to evaluate the pathologic response after NAC, but also support their application in other breast DCE-MRI vessel analysis that are waiting for a reliable quantification method.

Choline-containing compounds quantification by 1H NMR spectroscopy using external reference and noise measurements.

Proton magnetic resonance spectroscopy ((1)H-MRS) is largely exploited in clinical settings to non-invasively investigate chemical compounds in human tissues. Applications of (1)H-MRS in oncology field are connected to the detection of abnormal levels of choline compounds in more active tumours, providing useful information for cancer diagnosis and treatment monitoring. Since benign lesions may also show presence of a choline peak, implementing absolute evaluation will help differentiating benign from malignant tumours. An external reference procedure was described to provide choline quantification in standard unit of measurements. Spectra were acquired on a 1.5 T scanner using both phantoms and healthy volunteers with a PRESS sequence. The implemented quantification procedure used metabolite and noise measurements on the spectrum to remove large part of scanner settings contributing to metabolites of interest. A standard quantification was also used to compare performances of the noise-based method. In vitro quantification had accuracy and precision in the range (95-99)% and (5-13)%, respectively. When applied to in vivo studies on healthy volunteers, the method provided very close values of choline concentration, more exactly (1.73 ± 0.24) mmol/l. The method proposed can quantify the proper choline content in phantoms as well as in human structures, as brain. The method is ease of use, computational costless and it can be rapidly calibrated and implemented in any centre.

Comparison between PUN and Tofts models in the quantification of dynamic contrast-enhanced MR imaging.

Dynamic contrast-enhanced study in magnetic resonance imaging (DCE-MRI) is an important tool in oncology to visualize tissues vascularization and to define tumour aggressiveness on the basis of an altered perfusion and permeability. Pharmacokinetic models are generally used to extract hemodynamic parameters, providing a quantitative description of the contrast uptake and wash-out. Empirical functions can also be used to fit experimental data without the need of any assumption about tumour physiology, as in pharmacokinetic models, increasing their diagnostic utility, in particular when automatic diagnosis systems are implemented on the basis of an MRI multi-parametric approach. Phenomenological universalities (PUN) represent a novel tool for experimental research and offer a simple and systematic method to represent a set of data independent of the application field. DCE-MRI acquisitions can thus be advantageously evaluated by the extended PUN class, providing a convenient diagnostic tool to analyse functional studies, adding a new set of features for the classification of malignant and benign lesions in computer aided detection systems. In this work the Tofts pharmacokinetic model and the class EU1 generated by the PUN description were compared in the study of DCE-MRI of the prostate, evaluating complexity of model implementation, goodness of fitting results, classification performances and computational cost. The mean R² obtained with the EU1 and Tofts model were equal to 0.96 and 0.90, respectively, and the classification performances achieved by the EU1 model and the Tofts implementation discriminated malignant from benign tissues with an area under the receiver operating characteristic curve equal to 0.92 and 0.91, respectively. Furthermore, the EU1 model has a simpler functional form which reduces implementation complexity and computational time, requiring 6 min to complete a patient elaboration process, instead of 8 min needed for the Tofts model analysis.

Computer-aided diagnosis for dynamic contrast-enhanced breast MRI of mass-like lesions using a multiparametric model combining a selection of morphological, kinetic, and spatiotemporal features.

PURPOSE: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a radiological tool for the detection and discrimination of breast lesions. The aim of this study is to evaluate a computer-aided diagnosis (CAD) system for discriminating malignant from benign breast lesions at DCE-MRI by the combined use of morphological, kinetic, and spatiotemporal lesion features. METHODS: Fifty-four malignant and 19 benign breast lesions in 51 patients were retrospectively evaluated. Images were acquired at two centers at 1.5 T. Mass-like lesions were automatically segmented after image normalization and elastic coregistration of contrast-enhanced frames. For each lesion, a set of 28 3D features were extracted: ten morphological (related to shape, margins, and internal enhancement distribution); nine kinetic (computed from signal-to-time curves); and nine spatiotemporal (related to the variation of the signal between adjacent frames). A support vector machine (SVM) was trained with feature subsets selected by a genetic search. Best subsets were composed of the most frequent features selected by majority rule. The performance was measured by receiver operator characteristics analysis with a stratified tenfold cross-validation and bootstrap method for confidence intervals. RESULTS: SVM training by the three separated classes of features resulted in an area under the curve (AUC) of 0.90 ± 0.04 (mean ± standard deviation), 0.87 ± 0.06, and 0.86 ± 0.06 for morphological, kinetic, and spatiotemporal feature, respectively. Combined training with all 28 features resulted in AUC of 0.96 ± 0.02 obtained with a selected feature subset composed by two morphological, one kinetic, and two spatiotemporal features. CONCLUSIONS: Quantitative combination of morphological, kinetic, and spatiotemporal features is feasible and provides a higher discriminating power than using the three different classes of features separately.

In vivo characterisation of soft tissue tumours by 1.5-T proton MR spectroscopy.

OBJECTIVES: To determine whether proton magnetic resonance spectroscopy (1H-MRS) can help differentiate between benign and malignant soft tissue lesions, and to assess if there is a correlation between 1H-MRS data and the mitotic index. METHODS: MR measurements were performed in 43 patients with soft tissue tumours >15 mm in diameter. Six cases were excluded for technical failure. Examinations were performed at 1.5 T using a single-voxel point resolved spectroscopy sequence (PRESS) with TR/TE = 2000/150 ms. The volume of interest was positioned within the lesion avoiding inclusion of necrotic regions. In all patients, a histological diagnosis was obtained and the corresponding mitotic index was also computed. 1H-MRS results and histopathological findings were compared using the chi-squared test and correlation coefficient. RESULTS: Choline was detected in 18/19 patients with malignant tumours and in 3/18 patients with benign lesions. The three benign lesions included one desmoid tumour, one ossificans myositis and one eccrine spiradenoma. Choline was not detected in 15 patients with benign lesions or in one patient with dermatofibrosarcoma protuberans. Resulting 1H-MRS sensitivity and specificity were 95% and 83% respectively. CONCLUSIONS: Absence of choline peak is highly predictive of benign tumours suggesting that 1H-MRS can help to differentiate malignant from benign tumours. KEY POINTS: • 1H-MRS may allow differentiation between benign and malignant soft tissue lesions • Absence of choline peak is highly predictive of benign soft tissue lesions • Malignant tumours with a mitotic index >2/10 HPF had a positive choline peak • A choline peak may still be identified in some benign tumours.

Phenomenological universalities: a novel tool for the analysis of dynamic contrast enhancement in magnetic resonance imaging.

Dynamic contrast enhancement in magnetic resonance imaging (DCE-MRI) is a promising tool for the clinical diagnosis of tumors, whose implementation may be improved through the use of suitable hemodynamic models. If one prefers to avoid assumptions about the tumor physiology, empirical fitting functions may be adopted. For this purpose, in this paper we discuss the exploitation of a recently proposed phenomenological universalities (PUN) formalism. In fact, we show that a novel PUN class may be used to describe the time-signal intensity curves in both healthy and tumoral tissues, discriminating between the two cases and thus potentially providing a convenient diagnostic tool. The proposed approach is applied to analysis of the DCE-MRI data relative to a study group composed of ten patients with spine tumors.

CT colonography before colonoscopy in subjects with positive faecal occult blood test. Preliminary experience.

PURPOSE: We report a preliminary evaluation of the performance of computed tomography colonography (CTC) systematically obtained before optical colonoscopy (OC) in subjects with positive faecal occult blood test (FOBT) within a population-based screening programme for colorectal cancer (CRC). MATERIALS AND METHODS: Seventy-nine subjects with positive FOBT from a regional screening programme were invited to perform same day CTC and OC. CTC was performed with standard bowel preparation. OC with segmental unblinding was the reference standard. A per-patient per-adenoma analysis was performed. RESULTS: Forty-nine of 79 subjects (62%) with positive FOBT adhered to the study and completed both examinations. Twenty-two (44.9%) of the 49 had a cancer or an adenoma ≥6 mm. Per-patient sensitivity, specificity, negative predictive value and positive predictive value for cancer or adenoma ≥6 mm were 95.5% (95%CI:77.2%-99.9%), 51.9% (95%CI:32.0%-71.3%), 93.3% (95%CI:68.1%-99.8%) and 61.8% (95%CI:43.6%-77.8%). CONCLUSIONS: In the setting of a FOBT-based screening programme for CRC, CTC showed a high sensitivity, but relatively low specificity and positive predictive value, for cancer and adenoma ≥6 mm. Probably performing CTC without faecal tagging as second line test after a positive FOBT is not a cost-effective strategy.

CT colonography: Project of High National Interest No. 2005062137 of the Italian Ministry of Education, University and Research (MIUR).

PURPOSE: The aim of this paper is to describe the Web site of the Italian Project on CT Colonography (Research Project of High National Interest, PRIN No. 2005062137) and present the prototype of the online database. MATERIALS AND METHODS: The Web site was created with Microsoft Office Publisher 2003 software, which allows the realisation of multiple Web pages linked through a main menu located on the home page. The Web site contains a database of computed tomography (CT) colonography studies in the Digital Imaging and Communications in Medicine (DICOM) standard, all acquired with multidetector-row CT according to the parameters defined by the European Society of Abdominal and Gastrointestinal Radiology (ESGAR). The cases present different bowel-cleansing and tagging methods, and each case has been anonymised and classified according to the Colonography Reporting and Data System (C-RADS). RESULTS: The Web site is available at http address www.ctcolonography.org and is composed of eight pages. Download times for a 294-Mbyte file were 33 min from a residential ADSL (6 Mbit/s) network, 200 s from a local university network (100 Mbit/s) and 2 h and 50 min from a remote academic site in the USA. The Web site received 256 accesses in the 22 days since it went online. CONCLUSIONS: The Web site is an immediate and up-to-date tool for publicising the activity of the research project and a valuable learning resource for CT colonography.

Value of endorectal MRI and MRS in patients with elevated prostate-specific antigen levels and previous negative biopsies to localize peripheral zone tumours.

AIM: To evaluate prospectively the role of endorectal magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) in detecting peripheral zone tumour in patients with total prostate-specific antigen (PSA) values>or=4 ng/ml and one or more negative transrectal ultrasound (TRUS) biopsy rounds. MATERIAL AND METHODS: Fifty-four consecutive men (mean age 65.4+/-5.2 years, mean total PSA 10.8+/-7.5 ng/ml), underwent a combined MRI-MRS examination with endorectal coil. MRI included transverse, coronal, and sagittal T2-weighted and transverse T1-weighted fast spin-echo sequences. MRS data were acquired using a double spin-echo point resolved spectroscopy (PRESS) sequence. A 10-site scheme was adopted to evaluate the prostate peripheral zone. A peripheral prostatic site was classified as suspicious if low intensity signal was present on T2-weighted images and/or if the choline+creatine/citrate ratio was >0.86. Following MRI-MRS all patients were submitted to a standard 10-core biopsy scheme to which from one to three supplementary samples were added from suspicious MRI and/or MRS sites. In per-patient analysis findings were considered true-positive if biopsy positive patients were classified as suspicious, irrespectively of lesion site indication. RESULTS: Prostate cancer (PC) was detected in 17 of 54 patients (31.5%); median Gleason score was 6 (range 4-8). On a per-patient basis sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were respectively 100, 64.9, 56.7, 100, and 75.9% for MRI; 82.2, 70.3, 57.7, 92.9, and 75.9% for MRS; and 100, 51.4, 48.6, 100, and 66.7% for combined MRI-MRS. In all the 17 PC patients, combined MRI-MRS correctly indicated the sites harbouring cancer, whereas both MRI and MRS gave erroneous indications in two patients. CONCLUSION: The results of the present study show that MRI alone might be able to select negative patients in whom further biopsies are unnecessary. The combination of MRI and MRS might be able to drive biopsies in suspicious sites and increase the cancer detection rate. Further studies are required to confirm these data.

Visualization of quantitative breast DCE-MRI functional parametric maps by dedicated image processing.

DCE-MRI is a diagnostic method that can visualize neoangiogenic-induced vascular changes. Typically, the analysis of these data is time-consuming and the visualization of the quantitative information on tumor vasculature, derivable from DCE-MRI, is not easy and comfortable. In this study, we propose a method to accelerate computation and analysis of DCE-MRI data, while making easy to use the functional information obtained from model-based functional analysis.

Diagnostic accuracy of portal-phase CT and MRI with mangafodipir trisodium in detecting liver metastases from colorectal carcinoma.

AIM: To compare the diagnostic accuracy of single section spiral computed tomography (CT) and magnetic resonance imaging (MRI) with tissue-specific contrast agent mangafodipir trisodium (MnDPDP) in the detection of colorectal liver metastases. MATERIAL AND METHODS: One hundred and twenty-five consecutive patients undergoing surgery for primary and/or metastatic disease were evaluated using CT (5 mm collimation and reconstruction interval, pitch 2), two-dimensional fast spoiled gradient echo (2D FSPGR) T1 and single shot fast-spin echo (SSFSE) T2 weighted breath-hold MRI sequences, performed before and after intravenous administration of MnDPDP. The reference standards were intraoperative ultrasound and histology. RESULTS: The per-patient accuracy of CT was 72.8 versus 78.4% for unenhanced MRI (p = 0.071) and 82.4% for MnDPDP-enhanced MRI (p = 0.005). MnDPDP-enhanced MRI appeared to be more accurate than unenhanced MRI but this was not significant (p = 0.059). The sensitivity of CT was 48.4% versus 58.1% for unenhanced MRI (p = 0.083) and 66.1% for MnDPDP-enhanced MRI (p = 0.004). The difference in specificity between procedures was not significant. The per-lesion sensitivity was 71.7, 74.9 and 82.7% for CT, unenhanced MRI, and MnDPDP-enhanced MRI, respectively; the positive predictive value of the procedures was respectively 84.0, 96.0 and 95.8%. MnDPDP-enhanced MRI provided a high level diagnostic confidence in 92.5% of the cases versus 82.5% for both unenhanced MRI and CT. The kappa value for inter-observer variability was >0.75 for all procedures. CONCLUSIONS: The diagnostic accuracy and sensitivity of MnDPDP-enhanced MRI is significantly higher than single section spiral CT in the detection of colorectal cancer liver metastases; no significant difference in diagnostic accuracy was observed between unenhanced MRI and MnDPDP-enhanced MRI.

CT colonography: screening in individuals at high risk for colorectal cancer.

The use of computed tomographic colonography (CTC) as a screening test for colorectal cancer is being advocated with growing enthusiasm by physicians and the public as stronger evidence of its validity and limited invasiveness emerges from the literature. Because the approach to surveillance of colorectal cancer depends on an individual's degree of risk category, which depends on familial and personal histories, it seems logical that the diagnostic performance and cost efficacy of screening CTC may differ according to the characteristics of the target population. Although CTC seems a valid option in low- to average-risk populations, pending a careful assessment of its cost and estimates of its cost efficacy, there are some important issues that should be addressed when it comes to considering its use in high-risk patients. The expected larger number of induced colonoscopies and higher false-positive rates are likely to have a great influence on CTC costs, but if its implementation causes a dramatic increase in the number of patients willing to undergo screening, thanks to its acceptability, then the cost efficacy ratio may ultimately become competitive with all other screening strategies for colorectal cancer. We strongly feel that large and well-conducted trials are needed to clarify the role of CTC in screening patients at increased risk of developing colorectal cancer.

Phase II trial of primary radiation therapy and concurrent chemotherapy for patients with locally advanced pancreatic cancer.

OBJECTIVES: Primary chemoradiotherapy for locally advanced pancreatic cancer (LAPC) may improve local control, curative resection rate and long-term survival. We performed a phase II study to evaluate toxicity and activity of primary radiation therapy and concurrent chemotherapy with gemcitabine (GEM) twice weekly in patients (pts) with LAPC. METHODS: From 6/1999 to 6/2003, 23 LAPC pts received GEM 100 mg/m2 twice weekly in the first 15 pts and 50 mg/m2 in the last 8 pts, concurrently with radiotherapy (1.8 Gy/day for a total dose of 45 Gy). RESULTS: The treatment was completed in 19/23 pts. Toxicities: G3-4 hematological toxicity occurred in 35 and 4% respectively; G3 nausea and vomiting and gastrointestinal toxicity in 30%. Clinical benefit was found in 10/18 pts (55%). Overall response: partial response rate 4/18 (22%); stable disease 13/18 (72%); progressive disease 1/18 (6%). Six pts underwent pancreaticoduodenectomy with extended lymphadenectomy (5/6 pts pT3, 1/6 pts microscopic cancer foci, 1/6 N+, 5/6 negative retroperitoneal margin). MEDIAN SURVIVAL: 14 months for the entire group, 12 months for unresected pts, 20 months for resected pts. CONCLUSIONS: The treatment with GEM twice weekly at 50 mg/m2 associated with radiotherapy (45 Gy) is feasible and permits to obtain clinical benefit in a good percentage of pts. Objective response, median survival, and local and systemic control are similar to other studies and need further improvement.

Ileocecal valve imaging on computed tomographic colonography.

BACKGROUND: The aim of our study was to describe the visualization, normal anatomy, and variations of the ileocecal valve with computed tomographic (CT) colonography to provide information about its optimal imaging. METHODS: We analyzed data in two- and three-dimensional rendering mode in 71 consecutive patients who underwent routine CT colonoscopy followed by conventional colonoscopy for confirmation of the radiologic findings. RESULTS: Complete visualization of the ileocecal valve was better achieved in the supine than in the prone position (82% vs. 62%, respectively); the ileocecal valve appeared in 64% of cases in the supine position when it was invisible in prone position (p < 0.0001). Partial visualization of the ileocecal valve was possible in 94% of cases. The ileocecal valve was of labial type in 76%, papillary type in 21%, and lipomatous in 3% of cases. The orifice was identified in 53% of ileocecal valves; in two cases of cecal carcinoma, the normal ileocecal valve morphology was grossly disrupted. CONCLUSION: The ileocecal valve was at least partly visualized by CT colonoscopy in 94% of cases, more frequently in the supine position. Its most common normal morphology is the labial type. The absence of orifice visualization alone is not a specific sign for neoplasia, but its presence helps distinguish physiologic bulging from neoplasia.

Dynamic contrast enhanced magnetic resonance imaging in monitoring bone metastases in breast cancer patients receiving bisphosphonates and endocrine therapy.

PURPOSE: To study the role of dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) in monitoring the response of bone metastases to endocrine therapy combined with bisphosphonates in patients with breast cancer. MATERIAL AND METHODS: Ten breast cancer patients with bone metastases who were to receive endocrine therapy and bisphosphonates were investigated prospectively by DCE-MRI. We chose a reference lesion for each patient who was studied at baseline, within 3 weeks from the second administration of bisphosphonates, and after 4 and 8 months from the initiation of medical treatment. Time/intensity curves, representing temporal changes of signal intensity in areas of interest in the context of the target lesions (ROI), were obtained for each DCE-MRI. RESULTS: Changes in the shape of the T/I curves suggesting tumor regression were seen shortly after the initiation of medical treatment in the three patients who had the most durable responses. CONCLUSION: DCE-MRI has the potential to detect early changes related to medical treatment in bone metastases from breast cancer. If confirmed in larger series, these data identify DCE-MRI as a diagnostic tool for evaluating new bone targeting antineoplastic agents.

[Use of virtual endoscopy with computerized tomography in the identification of colorectal neoplasms. Prospective study with symptomatic patients]. / Impiego dell'endoscopia virtuale con Tomografia Computerizzata nell'identificazione delle neoplasie colorettali. Studio prospettico in pazienti sintomatici.

INTRODUCTION: Aim of this study was to evaluate the sensitivity of virtual colonoscopy (CT colonography) in the identification of colorectal cancer and to define the limitations and the advantages of this imaging modality, as well as indications to the examination. MATERIAL AND METHODS: We examined prospectively 62 symptomatic patients aged 36 to 82 years (28 women and 34 men). All patients underwent both conventional and virtual colonoscopy on the same day; the conventional examination allowed exploration of the entire colon. RESULTS: Conventional colonoscopy identified 89 lesions 3-50 mm in diameter, namely 84 benign and 5 malignant lesions. No lesions were identified in 12 patients. CT colonography identified 52 of the 89 lesions, with 57.1% diagnostic accuracy. There were 11 false positives (82.5% positive predictive value and 52.2% specificity) and 37 false negatives (24.5% negative predictive value and 58.4% sensitivity). Sensitivity was significantly higher (85.7%) for polyps > or = 1 cm. CONCLUSIONS: Virtual colonoscopy is an imaging modality with good diagnostic yield, well tolerated by patients and with great potentials for further development. We suggest that the examination be performed in symptomatic patients who cannot undergo total colonoscopy or refuse the other imaging modalities. Further studies are warranted in larger series of patients, possibly introducing it in screening programs.