Pier Carlo Muzzio

Digital breast tomosynthesis versus digital mammography: a clinical performance study

ObjectiveTo compare the clinical performance of digital breast tomosynthesis (DBT) with that of full-field digital mammography (FFDM) in a diagnostic population.MethodsThe study enrolled 200 consenting women who had at least one breast lesion discovered by mammography and/or ultrasound classified as doubtful or suspicious or probably malignant. They underwent tomosynthesis in one view [mediolateral oblique (MLO)] of both breasts at a dose comparable to that of standard screen-film mammography in two views [craniocaudal (CC) and MLO]. Images were rated by six breast radiologists using the BIRADS score. Ratings were compared with the truth established according to the standard of care and a multiple-reader multiple-case (MRMC) receiver-operating characteristic (ROC) analysis was performed. Clinical performance of DBT compared with that of FFDM was evaluated in terms of the difference between areas under ROC curves (AUCs) for BIRADS scores.ResultsOverall clinical performance with DBT and FFDM for malignant versus all other cases was not significantly different (AUCs 0.851 vs 0.836, p = 0.645). The lower limit of the 95% CI or the difference between DBT and FFDM AUCs was −4.9%.ConclusionClinical performance of tomosynthesis in one view at the same total dose as standard screen-film mammography is not inferior to digital mammography in two views.

Utility of choline positron emission tomography/computed tomography for lymph node involvement identification in intermediate- to high-risk prostate cancer: a systematic literature review and meta-analysis.

CONTEXT Determination of tumour involvement of regional lymph nodes in patients with prostate cancer (PCa) is of key importance for the proper planning of treatment. OBJECTIVES To provide a critical overview of published reports and to perform a meta-analysis about the diagnostic performance of 18F-choline and 11C-choline positron emission tomography (PET) or PET/computed tomography (CT) in the lymph node staging of PCa. EVIDENCE ACQUISITION A Medline, Web of Knowledge, and Google Scholar search was carried out to select English-language articles published before January 2012 that discussed the diagnostic performance of choline PET to individualise lymph node disease at initial staging in PCa patients. Articles were included only if absolute numbers of true-positive, true-negative, false-positive, and false-negative test results were available or derivable from the text and focused on lymph node metastases. Reviews, clinical reports, and editorial articles were excluded. All complete studies were reviewed; thus qualitative and quantitative analyses were performed. EVIDENCE SYNTHESIS From the year 2000 to January 2012, we found 18 complete articles that critically evaluated the role of choline PET and PCa at initial staging. The meta-analysis was carried out and consisted of 10 selected studies with a total of 441 patients. The meta-analysis provided the following results: pooled sensitivity 49.2% (95% confidence interval [CI], 39.9-58.4) and pooled specificity 95% (95% CI, 92-97.1). The area under the curve was 0.9446 (p<0.05). The heterogeneity ranged between 22.7% and 78.4%. The diagnostic odds ratio was 18.999 (95% CI, 7.109-50.773). CONCLUSIONS Choline PET and PET/CT provide low sensitivity in the detection of lymph node metastases prior to surgery in PCa patients. A high specificity has been reported from the overall studies. Studies carried out on a larger scale with a homogeneous patient population together with the evaluation of cost effectiveness are warranted.

The Potential of Restaging in the Prediction of Pathologic Response After Preoperative Chemoradiotherapy for Rectal Cancer

BackgroundWe performed this study to prospectively evaluate the postchemoradiotherapy performance of transrectal ultrasonography (TRUS), pelvic computed tomography (CT) scan and magnetic resonance imaging (MRI), and endoscopic biopsies for predicting the pathologic complete response of rectal cancer patients.MethodsFour weeks after completion of preoperative chemoradiotherapy, 46 consecutive patients with mid to low rectal cancer were prospectively evaluated by proctoscopy, TRUS, and pelvic CT scan and MRI. On the basis of T and N status, patients were classified as T0 or T1–4 and N-negative or N-positive. For each staging modality used, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were calculated. Findings were compared with the pathologic tumor-node-metastasis stage.ResultsOn histopathologic analysis, 12 patients had pT0 and 34 had pT1–4 lesions; out of 45 assessable patients, 9 were N-positive. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in predicting T status (T0 vs. T ≥1) were 77%, 33%, 74%, 36%, and 64%, respectively, for TRUS; 100%, 0%, 74%, not assessable, and 74% for CT; and 100%, 0%, 77%, not assessable, and 77% for MRI. The corresponding figures in predicting N status (N-negative vs. N-positive) were, respectively, 37%, 67%, 21%, 81%, and 61% for TRUS; 78%, 58%, 32%, 91%, and 62% for CT; and 33%, 74%, 25%, 81%, and 65% for MRI.ConclusionsCurrent rectal cancer staging modalities after chemoradiotherapy allow good prediction of node-negative cases, although none of them is able to predict the pathologic complete response on the rectal wall.

Rectal cancer: CT local staging with histopathologic correlation.

AbstractBackground: Many surgical options, eventually combined with neoadjuvant therapy, are available for the treatment of rectal cancer. Preoperative staging is essential to plan the correct treatment. Our aim was to evaluate the diagnostic accuracy of computed tomography (CT) in the local staging of rectal cancer. Methods: Between February 1995 and May 2000, 105 patients (65 male, 40 female; mean age = 58, range = 36–88 years) after preoperative locoregional CT staging underwent rectal resection for rectal cancer. In all patients, radiologic T and N staging was verified with pathologic examination of excised specimens. Patients were examined after air insufflation of the ampulla, during intravenous contrast injection; analysis of the rectoanal region was performed with thin (3–5 mm) contiguous slices. For T staging, Tis-T2, T3, and T4 groups were considered. For N staging, two groups of patients were considered: in 52 patients, N+ stage was attributed to all visible lymph nodes; in the other 53 patients, only lymph nodes >5 mm were recorded as N+. Results: Pathologic examination showed 61 T1–T2, 40 T3, and four T4 tumors; CT examination correctly identified 50 T1–T2 (81.9%), 33 T3 (82.5%), and three T4 (75%) lesions. With regard to N stage, pathologic examination in the first group (52 patients) showed only 11 cases of lymph node involvement. CT examination detected all 11 true-positive lymph nodes but overestimated 30 false-positive cases. In the second group (53 patients), pathology showed 26 cases of nodal involvement: CT examination identified 23 true-positive, 19 true-negative, eight false-positive, and three false-negative lymph nodes. Conclusion: CT correctly staged 86 (82%) of 105 lesions. Overestimation occurred in T2 patients (11of 61, 18%) and underestimation in T3 patients (seven of 33, 21%), in accordance with other reports dealing with superior accuracy of endorectal ultrasonography in local staging of early disease. Conversely, the criterion we suggest for evaluating metastatic perirectal lymph nodes (diameter > 5 mm) provided 79.2% diagnostic accuracy, 88.5% sensitivity, and 86.5% negative predictive value. This can be useful in those patients in whom prompt surgery, soon after radiochemotherapy in the case of nodal involvement, may likely be curative. With further improvement with spiral CT in local staging and nodal involvement, a larger number of transanal curative resections can be predicted.

Prospective assessment of imaging after preoperative chemoradiotherapy for rectal cancer.

BACKGROUND The aim of the study was to assess the accuracy of imaging techniques in predicting pathologic tumor (ypT), node (ypN) stages and the circumferential resection margin (ypCRM) status of rectal cancers after preoperative chemoradiotherapy (CRT). METHODS Using pelvic computed tomography (CT), magnetic resonance imaging (MRI), and endorectal ultrasound (ERUS), 90 consecutive patients with locally advanced mid-to-low rectal cancer were prospectively assessed. Postirradiation T and N stages and infiltration of the CRM, as assessed by CT, MRI and ERUS, were compared with histopathologic findings. RESULTS The accuracy of ypT staging was low, whatever the imaging technique used (37% by CT, 34% by MRI, and 27% by ERUS), the most frequent inaccuracy being overstaging. Imaging showed a good specificity and good negative predictive values (NPV) when mural staging was grouped into ypT ≤ 3 and ypT4 categories; in particular, ERUS achieved a 92% specificity and 95% NPV. CRM involvement was correctly predicted in 71% of patients by CT (74% specificity; 93% NPV) and in 85% by MRI (88% specificity; 95% NPV). The accuracy for nodal staging was 62%, 68%, and 65% by CT, MRI and ERUS, respectively; the corresponding NPV were 88%, 78%, and 76%. CONCLUSION Current imaging techniques are inaccurate in restaging rectal cancer after CRT but are useful in predicting T ≤ 3 tumors, cases with negative nodes and tumor-free CRM. These findings may be of clinical relevance for planning less invasive surgery.

Gamma-radiation upregulates MHC class I/II and ICAM-I molecules in multiple myeloma cell lines and primary tumors

SummaryThe γ-irradiation of normal cells causes an increased synthesis of specific proteins. However, few studies have described the effects of high doses of irradiation on the expression of cell surface antigens in tumor cells. This study analyzed the effects of high doses of γ-irradiation on the surface antigen expression of Major Histocompatability Complex (MHC) class I/II and intercellular adhesion molecule-1 (ICAM-I) in human multiple myeloma (MM) cell lines ARP-1, ARK-RS, and 10 MM primary tumors. The expression of surface antigens was evaluated by fluorescence-activated cell sorter analysis at different time points, following the exposure to high doses of γ-irradiation. Doses of 10,000 and 15,000 cGy were no0105 sufficient to totally block cell replication in both cell lines and primary tumors; cell replication was able to be inhibited completely only at 18,000 cGy. Lower doses (10,000 cGy) and lethal doses of irradiation (i.e., 15,000 and 18,000 cGy) increased the expression of all surface antigens present on the cells before irradiation. Essentially, such upregulation was shown to be dose dependent, with higher radiation doses resulting in higher antigen expression. Furthermore, when the kinetics of this upregulation were studied 3 and 6 d after irradiation, there was a constant increase in antigen expression in MM cells. These findings suggest that upregulation of costimulatory molecules, such as of MHC class I/II antigens and ICAM-1 molecules in MM patients treated by γ-radiation, can increase the immunogenicity of the tumor cells. In light of these findings, radiotherapy combined with immunotherapy might be considered in relapsing patients after receiving the standard treatment.

Early bone marrow metastasis detection: the additional value of FDG-PET/CT vs. CT imaging.

OBJECTIVE To assess the addition value of ¹⁸F-Fluorodeoxyglucose (FDG) PET/computed tomography (FDG-PET/CT) vs. CT in detecting early metastatic deposits in bone marrow (BM). METHODS From January 2009 to December 2010, 198 consecutive patients (88 male, 110 female; median age: 64 years) were retrospectively examined. All patients underwent ¹⁸F-FDG-PET/CT for disease evaluation: 65 for lung cancer, 66 for breast cancer, 57 for lymphoma and 10 for multiple myeloma. All scans were reviewed by a radiologist and a specialist in nuclear medicine for the identification of bone lesions. The presence of BM metastases was confirmed by biopsy, sequential PET/CT scan or magnetic resonance imaging when available. A patient-based analysis was performed. RESULTS Investigating the presence of skeletal metastasis, 94 (48%) patients had positive and 104 (52%) negative CT scan whereas 110 (56%) had positive and 88 (44%) negative FDG-PET/CT scan (P<0.001). The two imaging modalities were concordant in 178 (90%) patients for bone lesions; on the contrary 20 (10%) patients had discordant results (P<0.001). In 21 out of 178 concordant patients BM lesions were identified both in CT and FDG-PET, whereas nine out of the 20 discordant patients showed BM involvement at PET/CT only. Overall, PET/CT was able to identify 30 (15%) patients with BM lesions. In these latter patients, the maximum standardized uptake value (SUVmax) for BM metastases was 7.9±4.5 (range: 3.1-19.0), resulting slightly higher in patients with negative than positive CT scan (8.3±5.1 vs. 7.8±4.3, respectively; P=0.79). CONCLUSIONS FDG-PET/CT resulted more accurate than CT in early detection of BM metastases. The FDG-PET/CT images improve the staging of about 15% of our study population. PET/CT detected BM lesions mainly on the basis of their increased metabolic activity rather than on anatomical alterations. Moreover, it provided an accurate identification of tumour viability that was useful for treatment planning and follow-up.

Combination of one-view digital breast tomosynthesis with one-view digital mammography versus standard two-view digital mammography: per lesion analysis

AbstractObjectiveTo evaluate the clinical value of combining one-view mammography (cranio-caudal, CC) with the complementary view tomosynthesis (mediolateral-oblique, MLO) in comparison to standard two-view mammography (MX) in terms of both lesion detection and characterization.MethodsA free-response receiver operating characteristic (FROC) experiment was conducted independently by six breast radiologists, obtaining data from 463 breasts of 250 patients. Differences in mean lesion detection fraction (LDF) and mean lesion characterization fraction (LCF) were analysed by analysis of variance (ANOVA) to compare clinical performance of the combination of techniques to standard two-view digital mammography.ResultsThe 463 cases (breasts) reviewed included 258 with one to three lesions each, and 205 with no lesions. The 258 cases with lesions included 77 cancers in 68 breasts and 271 benign lesions to give a total of 348 proven lesions. The combination, DBT(MLO)+MX(CC), was superior to MX (CC+MLO) in both lesion detection (LDF) and lesion characterization (LCF) overall and for benign lesions. DBT(MLO)+MX(CC) was non-inferior to two-view MX for malignant lesions.ConclusionsThis study shows that readers’ capabilities in detecting and characterizing breast lesions are improved by combining single-view digital breast tomosynthesis and single-view mammography compared to two-view digital mammography.Key Points• Digital breast tomosynthesis is becoming adopted as an adjunct to mammography (MX) • DBT(MLO)+MX(CC)is superior to MX(CC+MLO)in lesion detection (overall and benign lesions) • DBT(MLO)+MX(CC)is non-inferior to MX(CC+MLO)in cancer detection • DBT(MLO)+MX(CC)is superior to MX(CC+MLO)in lesion characterization (overall and benign lesions) • DBT(MLO)+MX(CC)is non-inferior to MX(CC+MLO)in characterization of malignant lesions

Geometry of human vascular system: Is it an obstacle for quantifying antiangiogenic therapies?

It is now recognized that all human natural and diseased anatomic systems are characterized by irregular shapes and very complex behaviors. In geometrical terms, tumor vascularity (which is the result of a nonlinear dynamic process called angiogenesis) is an archetypal anatomic system that irregularly fills a 3-dimensional Euclidean space. This characteristic, together with the highly variable nature of vessel shapes and surfaces, leads to considerable spatial and temporal heterogeneity in the delivery of oxygen, nutrients, and drugs, and the removal of metabolites. Although these biologic features have been well established, the quantitative analysis of neovascularity in 2-dimensional histologic sections still fails to view its architecture as a non-Euclidean geometrical object, thus allowing errors in visual interpretation and discordant results concerning the same tumor from different laboratories. We discuss here the tumor-induced vascular system as a fractal object, and what changes this new way of observing may bring to the quantification of effective antiangiogenic therapies.

Cancer initiation and progression: an unsimplifiable complexity.

BackgroundCancer remains one of the most complex diseases affecting humans and, despite the impressive advances that have been made in molecular and cell biology, how cancer cells progress through carcinogenesis and acquire their metastatic ability is still widely debated.ConclusionThere is no doubt that human carcinogenesis is a dynamic process that depends on a large number of variables and is regulated at multiple spatial and temporal scales. Viewing cancer as a system that is dynamically complex in time and space will, however, probably reveal more about its underlying behavioural characteristics. It is encouraging that mathematicians, biologists and clinicians continue to contribute together towards a common quantitative understanding of cancer complexity. This way of thinking may further help to clarify concepts, interpret new and old experimental data, indicate alternative experiments and categorize the acquired knowledge on the basis of the similarities and/or shared behaviours of very different tumours.