Daniele Regge

Monitoring Response to Primary Chemotherapy in Breast Cancer using Dynamic Contrast-enhanced Magnetic Resonance Imaging

AbstractPurpose. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows analysis of both tumor volume and contrast enhancement pattern using a single tool. We sought to investigate whether DCE-MRI could be used to predict histological response in patients undergoing primary chemotherapy (PCT) for breast cancer. Patients and methods. Thirty patients with breast cancer, clinical diameter >3 cm or stage III A/B, received anthracycline and taxane based PCT. DCE-MRI was performed at the baseline, after two cycles and after four cycles of PCT, before surgery. Histological response was assessed using a five-point scheme. Grade 4 (small cluster of dispersed residual cancer cells) and grade 5 (no residual viable cancer cell) were defined as a major histopathological response (MHR). Results. Univariate analysis showed that a >65% reduction in the tumor volume and a reduction in the early enhancement ratio (ECU) after two cycles of PCT were associated with a MHR. Multivariate analysis revealed that tumor volume reduction after two cycles of PCT was independently associated with a MHR (odds ratio [OR] 39.968, 95% confidence interval [CI] 3.438–464.962, p < 0.01). ECU reduction was still associated with a MHR (OR 2.50, 95% CI 0.263–23.775), but it did not retain statistical significance (p = 0.42). Combining tumor volume and ECU reduction after two cycles of PCT yielded a 93% diagnostic accuracy in identifying tumors achieving a pathological complete response (pCR) (histopathological grade 5). Conclusions. DCE-MRI allows prediction of the effect of neoadjuvant chemotherapy in breast cancer. Although in our study tumor volume reduction after two cycles had the strongest predictive value, DCE-MRI has the potential to provide functional parameters that could be integrated to optimize neoadjuvant chemotherapy strategies.

Dual-targeted therapy with trastuzumab and lapatinib in treatment-refractory, KRAS codon 12/13 wild-type, HER2-positive metastatic colorectal cancer (HERACLES): a proof-of-concept, multicentre, open-label, phase 2 trial

BACKGROUND We previously found that dual HER2 blockade with trastuzumab and lapatinib led to inhibition of tumour growth in patient-derived xenografts of HER2-amplified metastatic colorectal cancer. In this study, we aimed to assess the antitumour activity of trastuzumab and lapatinib in patients with HER2-positive colorectal cancer. METHODS HERACLES was a proof-of-concept, multicentre, open-label, phase 2 trial done at four Italian academic cancer centres. We enrolled adult patients with KRAS exon 2 (codons 12 and 13) wild-type and HER2-positive metastatic colorectal cancer refractory to standard of care (including cetuximab or panitumumab), an Eastern Cooperative Oncology Group performance status of 0 or 1, and at least one measurable lesion. We defined HER2 positivity in tumour samples by use of immunohistochemistry and fluorescence in-situ hybridisation in accordance with our previously validated colorectal cancer-specific diagnostic criteria. Eligible patients received intravenous trastuzumab at 4 mg/kg loading dose followed by 2 mg/kg once per week, and oral lapatinib at 1000 mg per day until evidence of disease progression. The primary endpoint was the proportion of patients achieving an objective response (defined as complete response or partial response), which was assessed by independent central review in the intention-to-treat population. This trial is registered with EudraCT, number 2012-002128-33. FINDINGS Between Aug 27, 2012, and May 15, 2015, we screened 914 patients with KRAS exon 2 (codons 12 and 13) wild-type metastatic colorectal cancer and identified 48 (5%) patients with HER2-positive tumours, although two died before enrolment. Of these patients, 27 were eligible for the trial. All were evaluable for response. At the time of data cutoff on Oct 15, 2015, with a median follow-up of 94 weeks (IQR 51-127), eight (30%, 95% CI 14-50) of 27 patients had achieved an objective response, with one patient (4%, 95% CI -3 to 11) achieving a complete response, and seven (26%, 95% CI 9-43) achieving partial responses; 12 (44%, 95% CI 25-63) patients had stable disease. Six (22%) of 27 patients had grade 3 adverse events, which consisted of fatigue in four patients, skin rash in one patient, and increased bilirubin concentration in one patient. No grade 4 or 5 adverse events were reported. We detected no drug-related serious adverse events. INTERPRETATION The combination of trastuzumab and lapatinib is active and well tolerated in treatment-refractory patients with HER2-positive metastatic colorectal cancer. FUNDING Associazione Italiana Ricerca Cancro (AIRC), Fondazione Oncologia Niguarda Onlus, and Roche.

Portal Vein Ligation as an Efficient Method of Increasing the Future Liver Remnant Volume in the Surgical Treatment of Colorectal Metastases

OBJECTIVE To compare the volumetric increase of segments 2 and 3, segment 4, and the caudate lobe after portal vein ligation (PVL) and portal vein embolization (PVE). The small size of the remnant liver and chemotherapy-induced liver injury increase the risk of postoperative hepatic insufficiency after major hepatic resection for colorectal liver metastases. Portal vein ligation has been suggested to be less effective than embolization in inducing hypertrophy of the remnant liver. DESIGN, SETTING, AND PATIENTS We retrospectively reviewed 48 patients with colorectal liver metastases who underwent PVL (n = 17) or PVE (n = 31) at the Istituto per la Ricerca e la Cura del Cancro or the Institut Paoli-Calmette from March 1, 2000, through August 31, 2006. MAIN OUTCOME MEASURES To compare the volume increase of segments 2 and 3, segment 4, and of the caudate lobe in patients who have undergone PVL or PVE in preparation for a major hepatic resection. RESULTS There were no deaths related to PVE or PVL. Portal vein ligation was associated with resection of synchronous colorectal cancer in 16 patients. Resection of a liver metastasis in the remnant liver was performed in 11 patients. The median estimated baseline volume of segments 2 and 3 was 17.7% in the PVL group and 17.5% in the PVE group (P = .72). After PVL or PVE, it increased to 26.9% and 24.7%, respectively (P = .95), for volumetric increases of 43.1% and 53.4%, respectively (P = .39). The volumetric increases of segment 4 and the caudate lobe were similar. CONCLUSION Portal vein ligation is as effective as PVE in inducing hypertrophy of the remnant liver volume.

Pain relief following percutaneous vertebroplasty: results of a series of 283 consecutive patients treated in a single institution

The aim of this study was to assess if percutaneous vertebroplasty (PVP) could relieve back pain, reduce drug consumption, and improve the mobility of patients with metastases and vertebral compression fractures. From August 2002 to July 2004, 283 patients (216 females; mean age: 73.8 ± 9.9 years) underwent PVP on 749 vertebrae. Pain was evaluated with the pain intensity numeric rating scale (PI-NRS) (0 = no pain; 10 = worst pain) before the procedure and at the end point in September 2004 (follow-up:1–24 months; median: 7 months). A reduction of at least two points of the PI-NRS score was considered clinically relevant. Two hundred four patients were available for evaluation at the end point. Overall results showed a reduction of the median pain score from 8 at baseline to 1 at the end point (p < 0.0001); a clinically relevant pain reduction was observed in 176/205 patients (86%); 89/147 patients (61%) gave up a brace support (p < 0.0001); and 117/190 patients (62%) gave up drug therapy. Results were similar in different subgroups stratified according to age, underlying pathology, number of fractured or treated vertebrae, and length of follow-up. This study adds evidence that PVP is effective in treating painful vertebral fractures. A significant reduction in drug assumption and significant mobility improvement can also be achieved.

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.

Induction Gemcitabine and Oxaliplatin Therapy Followed by a Twice-Weekly Infusion of Gemcitabine and Concurrent External-Beam Radiation for Neoadjuvant Treatment of Locally Advanced Pancreatic Cancer A Single Institutional Experience

Chemoradiotherapy (CRT) may render curative resection feasible in patients with locally advanced pancreatic carcinoma (LAPC). The authors previously demonstrated the achievement of significant disease control and a median survival of 14 months by CRT in patients with LAPC. In this study, they evaluated the use of induction chemotherapy followed by a CRT neoadjuvant protocol.

The Roles of Multiparametric Magnetic Resonance Imaging, PCA3 and Prostate Health Index—Which is the Best Predictor of Prostate Cancer after a Negative Biopsy?

PURPOSE In patients with a negative prostate biopsy and persistent suspicion of prostate cancer, additional analyses such as the PCA3 score, PHI and multiparametric magnetic resonance imaging have been proposed to reduce the number of unnecessary repeat biopsies. In this study we evaluate the diagnostic accuracy of PCA3, PHI, multiparametric magnetic resonance imaging and various combinations of these tests in the repeat biopsy setting. MATERIALS AND METHODS A total of 170 patients with an initial negative prostate biopsy and persistent suspicion of prostate cancer were enrolled in this prospective study. The patients underwent measurements of the total prostate specific antigen and free prostate specific antigen rate, along with PHI, PCA3 tests and multiparametric magnetic resonance imaging before standard repeat biopsy that was performed by urologists blinded to the multiparametric magnetic resonance imaging results. Multivariate logistic regression models with various combinations of PCA3, PHI and multiparametric magnetic resonance imaging were used to identify the predictors of prostate cancer with repeat biopsy, and the performance of these models was compared using ROC curves, AUC analysis and decision curve analysis. RESULTS In the ROC analysis the most significant contribution was provided by multiparametric magnetic resonance imaging (AUC 0.936), which was greater than the contribution of the PHI+PCA3 model (p <0.001). In the multivariate logistic regression analysis only multiparametric magnetic resonance imaging was a significant independent predictor of prostate cancer diagnosis with repeat biopsy (p <0.001). The results of the decision curve analysis confirmed that the most significant improvement in the net benefit was provided by multiparametric magnetic resonance imaging. CONCLUSIONS Multiparametric magnetic resonance imaging provides high diagnostic accuracy in identifying patients with prostate cancer in the repeat biopsy setting compared with PCA3 and PHI.

Magnetic resonance imaging and Orbscan assessment of the anterior chamber

PURPOSE: To evaluate the correlation between white‐to‐white (WTW) distance as assessed by Orbscan II (Bausch & Lomb) and high‐resolution magnetic resonance imaging (MRI) sulcus–sulcus (S–S) measures and to analyze the correlation between age and anterior chamber parameters. SETTING: Istituto per la Ricerca e la Cura del Cancro, Candiolo, Torino, Italy. METHODS: Eighty‐eight patients had MRI with a 1.5 Tesla imager (GE Medical Systems) using a 3‐inch circular coil. T1 weighted fast spin‐echo scans were performed on the axial plane. Orbscan II was also used to measure WTW distance, K, anterior chamber depth (ACD), and lens curvature. One eye was randomly selected for analysis. Measures were compared using Spearman correlation, paired Student t test, and analysis of variance (ANOVA; post hoc: Scheffé). Intersession variability was performed in 10 patients. Ten MRI images were randomly selected and measured by 2 operators in a masked fashion (intrasession variability). RESULTS: Intersession and intrasession correlation was good for MRI (r = 0.89 and r = 0.92, respectively), and intersession was good for Orbscan (r = 0.91). When comparing Orbscan II and MRI results, the ACD was well correlated and not significantly different, whereas the S–S and the WTW measures were not correlated and significantly different. Lens thickness and lens diameter were directly correlated with age; S–S, WTW, lens curvature, and ACD were inversely correlated with age. CONCLUSIONS: Current methods of measuring the WTW were poorly correlated with anatomical measures. The S–S diameter and other anterior chamber structures significantly change with age, which could give rise to potential problems with posterior chamber phakic intraocular lens sizing position.

Impact of computer-aided detection on the cost-effectiveness of CT colonography.

PURPOSE To analyze the cost-effectiveness of adding computer-aided detection (CAD) to a computed tomographic (CT) colonography screening program and to compare it with other options of colorectal cancer (CRC) prevention. MATERIALS AND METHODS The cost-effectiveness of screening strategies by using CT colonography with and without CAD, flexible sigmoidoscopy (FS), and optical colonoscopy were compared by using a Markov-based computer model. In the model, a hypothetical population of 100,000 persons aged 50 years underwent colorectal screening every 10 years. Baseline sensitivities for both experienced and inexperienced readers and the incremental accuracy when adding CAD were estimated from a systematic review of the literature. RESULTS At baseline, the addition of CAD resulted in 9% and 2% increases in CRC prevention rates for inexperienced and experienced readers, respectively, when compared with CT colonography without CAD. Assuming a CAD cost of

Endorectal magnetic resonance imaging and magnetic resonance spectroscopy to monitor the prostate for residual disease or local cancer recurrence after transrectal high-intensity focused ultrasound

50 per CT colonography, the overall program costs increased by only 3%-5%, largely because of the substantial reduction in CRC-related costs. The incremental cost-effectiveness of CT colonography with CAD compared with CT colonography without CAD was