Giuseppe Petralia

CT perfusion in oncology: how to do it

Abstract Robust technique and accurate data analysis are required for reliable computed tomography perfusion (CTp) imaging. Multislice CT is required for high temporal resolution scanning; 16-slice (or 64-slice) scanners are preferred for adequate volume coverage. After tumour localization, the volume of CTp imaging has to be positioned to include the maximum visible area of the tumour and an adequate arterial vessel. Dynamic scans at high temporal resolution (at least 1-s gantry rotation time) are performed to visualize the first pass of contrast agent within the tumour; repeated scans with low temporal resolution can be planned for late enhancement assessment. A short bolus of conventional iodinated contrast agent, preferably with high iodine concentration, is power injected at a high flow rate (>4 ml/s) in the antecubital vein. The breath-hold technique is required for CTp imaging of the chest and upper abdomen to avoid respiratory motion; free breathing is adequate for CTp imaging of the head, neck and pelvis. Using dedicated software, a region of interest (ROI) has to be placed in an adequate artery (as arterial input) to obtain density–time curves; according to different kinetic models, colour maps of different CTp parameters are generated and generally overlaid on CT images. Additional ROIs can be positioned in the tumour, and in all other parts of the CTp volume, to obtain the values of the CTp parameters within the ROI.

METastasis Reporting and Data System for Prostate Cancer: Practical Guidelines for Acquisition, Interpretation, and Reporting of Whole-body Magnetic Resonance Imaging-based Evaluations of Multiorgan Involvement in Advanced Prostate Cancer

Context Comparative reviews of whole-body magnetic resonance imaging (WB-MRI) and positron emission tomography/computed tomography (CT; with different radiotracers) have shown that metastasis detection in advanced cancers is more accurate than with currently used CT and bone scans. However, the ability of WB-MRI and positron emission tomography/CT to assess therapeutic benefits has not been comprehensively evaluated. There is also considerable variability in the availability and quality of WB-MRI, which is an impediment to clinical development. Expert recommendations for standardising WB-MRI scans are needed, in order to assess its performance in advanced prostate cancer (APC) clinical trials. Objective To design recommendations that promote standardisation and diminish variations in the acquisition, interpretation, and reporting of WB-MRI scans for use in APC. Evidence acquisition An international expert panel of oncologic imagers and oncologists with clinical and research interests in APC management assessed biomarker requirements for clinical care and clinical trials. Key requirements for a workable WB-MRI protocol, achievable quality standards, and interpretation criteria were identified and synthesised in a white paper. Evidence synthesis The METastasis Reporting and Data System for Prostate Cancer guidelines were formulated for use in all oncologic manifestations of APC. Conclusions Uniformity in imaging data acquisition, quality, and interpretation of WB-MRI are essential for assessing the test performance of WB-MRI. The METastasis Reporting and Data System for Prostate Cancer standard requires validation in clinical trials of treatment approaches in APC. Patient summary METastasis Reporting and Data System for Prostate Cancer represents the consensus recommendations on the performance, quality standards, and reporting of whole-body magnetic resonance imaging, for use in all oncologic manifestations of advanced prostate cancer. These new criteria require validation in clinical trials of established and new treatment approaches in advanced prostate cancer.

Perfusion computed tomography for monitoring induction chemotherapy in patients with squamous cell carcinoma of the upper aerodigestive tract: correlation between changes in tumor perfusion and tumor volume.

Objective: The aim of this study was to assess the potential of perfusion computed tomography (CTp) for monitoring induction chemotherapy in patients with squamous cell carcinoma (SCCA) of the upper aerodigestive tract. Materials and Methods: Twenty-five patients with advanced SCCA underwent CTp and volumetric CT before and after induction chemotherapy. Perfusion CT parameters were calculated in the tumor, normal tissue, and muscles and correlated with tumor volume. Results: The blood flow (BF), blood volume (BV), and permeability surface were significantly higher, and the mean transit time was significantly lower in the tumor than in the normal tissue. The tumor BF and BV significantly decreased, and the mean transit time significantly increased after the therapy; decrease in BF and BV correlated with tumor volume reduction after chemotherapy. The baseline tumor BV was significantly lower in nonresponders compared with that in responders. Conclusions: In patients with SCCA, CTp showed potential for monitoring induction chemotherapy, reduction in tumor BF and BV correlated with reduction of tumor volume after chemotherapy, and baseline tumor BV may predict response to chemotherapy.

Salvage therapy of intraprostatic failure after radical external-beam radiotherapy for prostate cancer: A review

Radical external-beam radiotherapy (EBRT) is a standard treatment for prostate cancer (PC) patients. Despite this, the rate of intraprostatic relapses after primary EBRT is still not negligible. There is no consensus on the most appropriate management of these patients after EBRT failure. Treatment strategies after PC relapse are strongly influenced by the effective site of the tumor recurrence, and thus the instrumental evaluation with different imaging techniques becomes crucial. In cases of demonstrated intraprostatic failure, several systemic (androgen deprivation therapy) or local (salvage prostatectomy, cryotherapy, high-intensity focused ultrasound, brachytherapy, stereotactic EBRT) treatment options could be proposed and are currently delivered by clinicians with a variety of results. In this review we analyze the correct definition of intraprostatic relapse after radiotherapy, focusing on the recent developments in imaging to detect intraprostatic recurrence. Furthermore, all available salvage treatment options after a radiation therapy local failure are presented and thoroughly discussed.

Predicting Pathological Features at Radical Prostatectomy in Patients with Prostate Cancer Eligible for Active Surveillance by Multiparametric Magnetic Resonance Imaging

Purpose The aim of this study was to investigate the prognostic performance of multiparametric magnetic resonance imaging (mpMRI) and Prostate Imaging Reporting and Data System (PIRADS) score in predicting pathologic features in a cohort of patients eligible for active surveillance who underwent radical prostatectomy. Methods A total of 223 patients who fulfilled the criteria for “Prostate Cancer Research International: Active Surveillance”, were included. Mp–1.5 Tesla MRI examination staging with endorectal coil was performed at least 6–8 weeks after TRUS-guided biopsy. In all patients, the likelihood of the presence of cancer was assigned using PIRADS score between 1 and 5. Outcomes of interest were: Gleason score upgrading, extra capsular extension (ECE), unfavorable prognosis (occurrence of both upgrading and ECE), large tumor volume (≥0.5ml), and seminal vesicle invasion (SVI). Receiver Operating Characteristic (ROC) curves and Decision Curve Analyses (DCA) were performed for models with and without inclusion of PIRADS score. Results Multivariate analysis demonstrated the association of PIRADS score with upgrading (P<0.0001), ECE (P<0.0001), unfavorable prognosis (P<0.0001), and large tumor volume (P = 0.002). ROC curves and DCA showed that models including PIRADS score resulted in greater net benefit for almost all the outcomes of interest, with the only exception of SVI. Conclusions mpMRI and PIRADS scoring are feasible tools in clinical setting and could be used as decision-support systems for a more accurate selection of patients eligible for AS.

Perfusion computed tomography in patients with hepatocellular carcinoma treated with thalidomide: initial experience.

Objective: The objective of the study was to evaluate the role of perfusion computed tomography (CT) for monitoring and predicting therapy response in patients with hepatocellular carcinoma treated with thalidomide. Methods: Twenty-four patients with advanced hepatocellular carcinoma were treated with thalidomide. Perfusion and conventional CT were performed at baseline and every 2 months until disease progression. Baseline tumor size and enhancement characteristics, as well as baseline perfusion parameters and their changes after therapy, were explored and tested for association with therapy response. Results: Perfusion CT was feasible in 18 patients. Baseline tumor size and enhancement characteristics showed no predictive value, whereas baseline blood flow and blood volume were higher in patients with progressive disease (P < 0.042), with cutoff values for blood flow (16.7 mL/100 g per minute) and blood volume (1.84 mL/100 g) predicting progressive disease in 83.3% and 77.8% of patients, respectively. Significant changes were observed after 2, 4, and 6 months in blood flow (P < 0.031), blood volume after 4 months (P = 0.018), and mean transit time after 4 and 6 months (P = 0.030) in patients with stable disease at 6 months. Conclusions: Baseline blood flow and blood volume predicted response to therapy in our cohort.

Breast MR with special focus on DW-MRI and DCE-MRI

Abstract The use of magnetic resonance imaging (MRI) for the assessment of breast lesions was first described in the 1970s; however, its wide application in clinical routine is relatively recent. The basic principles for diagnosis of a breast lesion rely on the evaluation of signal intensity in T2-weighted sequences, on morphologic assessment and on the evaluation of contrast enhancement behaviour. The quantification of dynamic contrast behaviour by dynamic contrast-enhanced (DCE) MRI and evaluation of the diffusivity of water molecules by means of diffusion-weighted MRI (DW-MRI) have shown promise in the work-up of breast lesions. Therefore, breast MRI has gained a role for all indications that could benefit from its high sensitivity, such as detection of multifocal lesions, detection of contralateral carcinoma and in patients with familial disposition. Breast MRI has been shown to have a role in monitoring of neoadjuvant chemotherapy, for the evaluation of therapeutic results during the course of therapy. Breast MRI can improve the determination of the remaining tumour size at the end of therapy in patients with a minor response. DCE-MRI and DW-MRI have shown potential for improving the early assessment of tumour response to therapy and the assessment of residual tumour after the end of therapy. Breast MRI is important in the postoperative work-up of breast cancers. High sensitivity and specificity have been reported for the diagnosis of recurrence; however, pitfalls such as liponecrosis and changes after radiation therapy have to be carefully considered.

Capecitabine Initially Concomitant to Radiotherapy Then Perioperatively Administered in Locally Advanced Rectal Cancer

PURPOSE To evaluate the impact of neoadjuvant capecitabine, concomitant to radiotherapy, followed by capecitabine monotherapy, in operable locally advanced rectal cancer (LARC) by measuring pathologic response and conservative surgery rate, toxicity profile, and disease-free survival (DFS). METHODS AND MATERIALS From October 2002 to July 2006, a total of 51 patients affected by LARC (T3-T4 or any node positive tumor), received capecitabine (825 mg/m(2), orally, twice daily continuously) concomitant to radiotherapy on the pelvis (50.4 Gy/ 28 fractions), followed by two cycles of capecitabine (1,250 mg/m(2), orally, twice daily, 14 days on 7 days off) up until 2 weeks before surgery. Tailored adjuvant systemic treatment was discussed according to pathologic stage. RESULTS Of 51 patients, (median age 61 years, range 38-82 years; 19 women and 32 men; ECOG performance status 0/1/2: 46/4/1), 50 were evaluable for response: 18% complete pathologic remission; 12% T-downstaging, and 30% N-downstaging. One patient died before surgery from mesenteric stroke. Grade 3 acute toxicities were 2% diarrhea, 8% dermatitis, 2% liver function test elevation, and 2% hand-foot syndrome. Sphincter preservation rates for tumors < or =6 cm from the anal verge were 62% and 80% for the whole population. Median follow up was 43.0 months (range 0.8-68.6 months). Five-years DFS was 85.4% (95% CI = 75.3-95.4%). CONCLUSIONS Based on our study results, we conclude that this regimen is well tolerated and active and compares favorably with existing capecitabine-based approaches.

Quantification of variability in breath-hold perfusion CT of hepatocellular carcinoma: A step toward clinical use

PURPOSE To assess the variability of breath-hold perfusion computed tomography (CT) parameters and to investigate whether these measurements are affected by a commercial software upgrade in patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS Written informed consent was obtained from all participants in this institutional ethics committee-approved study. Perfusion CT examinations in HCC patients were prospectively analyzed by three readers. Two readers repeated their analysis after an interval of at least 4 weeks. Inter- and intraobserver agreement, as well as intersoftware agreement, were assessed with intraclass correlation coefficients (ICCs) and Bland-Altman limits of agreement (LoA), with adjustment for correlation between repeated measures. RESULTS Ninety-three breath-hold perfusion CT examinations were included from 23 HCC patients. The ICC between readers was very high (>0.91) for blood flow (BF), high (>0.84) for blood volume (BV), and lower (>0.30 and >0.39) for mean transit time (MTT) and permeability surface area product (PS), respectively, while ICC between readings was high (>0.80) for BF and BV, good (>0.75) for PS, and lower (>0.38) for MTT, irrespective of software version. By using the current software, the clinically relevant percentage of LoA between readers for BF were -33%; for BV, -39%; for MTT, 55%; and for PS, -93%. Between readings by the most expert reader, the clinically relevant LoA were -35% for BF,-43% for BV, 33% for MTT, and -79% for PS. BF, BV, and PS values were significantly higher and MTT values were significantly lower (P<.01) with the current software version relative to the previous version. CONCLUSION With the current CT perfusion software, only decreases between scans of HCC lesions of more than 35% for BF and 43% for BV, or an increase of more than 55% for MTT, could be considered beyond the analysis variability. The perfusion parameters obtained with the current and previous software versions were not exchangeable. The results of this study are specific for breath-hold perfusion CT of HCC and may not apply to different acquisition protocols and tumors.

Rationale for Modernising Imaging in Advanced Prostate Cancer

CONTEXT To effectively manage patients with advanced prostate cancer (APC), it is essential to have accurate, reproducible, and validated methods for detecting and quantifying the burden of bone and soft tissue metastases and for assessing their response to therapy. Current standard of care imaging with bone and computed tomography (CT) scans have significant limitations for the assessment of bone metastases in particular. OBJECTIVE We aimed to undertake a critical comparative review of imaging methods used for diagnosis and disease monitoring of metastatic APC from the perspective of their availability and ability to assess disease presence, extent, and response of bone and soft tissue disease. EVIDENCE ACQUISITION An expert panel of radiologists, nuclear medicine physicians, and medical physicists with the greatest experience of imaging in advanced prostate cancer prepared a review of the practicalities, performance, merits, and limitations of currently available imaging methods. EVIDENCE SYNTHESIS Meta-analyses showed that positron emission tomography (PET)/CT with different radiotracers and whole-body magnetic resonance imaging (WB-MRI) are more accurate for bone lesion detection than CT and bone scans (BSs). At a patient level, the pooled sensitivities for bone disease by using choline (CH)-PET/CT, WB-MRI, and BS were 91% (95% confidence interval [CI], 83-96%), 97% (95% CI, 91-99%), and 79% (95% CI, 73-83%), respectively. The pooled specificities for bone metastases detection using CH-PET/CT, WB-MRI, and BS were 99% (95% CI, 93-100%), 95% (95% CI, 90-97%), and 82% (95% CI, 78-85%), respectively. The ability of PET/CT and WB-MRI to assess therapeutic benefits is promising but has not been comprehensively evaluated. There is variability in the cost, availability, and quality of PET/CT and WB-MRI. CONCLUSIONS Standardisation of acquisition, interpretation, and reporting of WB-MRI and PET/CT scans is required to assess the performance of these techniques in clinical trials of treatment approaches in APC. PATIENT SUMMARY PET/CT and whole-body MRI scans have the potential to improve detection and to assess response to treatment of all states of advanced prostate cancer. Consensus recommendations on quality standards, interpretation, and reporting are needed but will require validation in clinical trials of established and new treatment approaches.