Marc Lemort

Discriminating cancer from noncancer tissue in the prostate by 3-dimensional proton magnetic resonance spectroscopic imaging: a prospective multicenter validation study.

Objectives:A prospective multicenter validation of the ability of 1H magnetic resonance spectroscopic imaging (MRSI) to distinguish cancer from noncancer tissues throughout the prostate with histopathology of the resected organ as the standard of reference. Materials and Methods:Institutional review board approval was obtained for all centers and all participating patients and volunteers provided written informed consent. Ninety-nine patients and 10 age-matched volunteers from 8 participating centers underwent magnetic resonance imaging and 3-dimensional MRSI with an endorectal coil at 1.5 T. Selected MRSI voxels were assigned to the peripheral zone (PZ), the central gland (CG), the periurethral area, and cancer tissue. Signal ratios of choline + creatine to citrate (CC/C) in spectra of these voxels were automatically calculated. Receiver operating characteristic curves were constructed to assess the accuracy by which this ratio can discriminate cancer from noncancer tissue. Results:A total of 70% of voxels in noncancer tissue and 90% of voxels in cancer tissue passed the quality check of the automatically fitted spectra. The median CC/C was significantly different between any noncancer and cancer tissue (P < 0.0001), but not between the different contributing centers. CC/C increased with cancer focus size (P = 0.0008) and certainty of voxel mapping to histopathologic cancer site (P < 0.0001). The area under the receiver operating characteristic curve for discriminating voxels of cancer tissue from noncancer tissue was 0.88 (confidence interval: 0.84–0.92) in the PZ and 0.76 (confidence interval: 0.71–0.81) in the CG. Conclusions:In patients with prostate cancer, recruited from different institutions, 3-dimensional MRSI is demonstrated to be a robust and quantitative technique, producing significantly different CC/C values for cancer compared with noncancer tissue for both the CG and the PZ.

Heterogeneity of Metabolic Response to Systemic Therapy in Metastatic Breast Cancer Patients

AIM The aim of this retrospective study was to describe the intra-individual heterogeneity of the ¹⁸F-labelled fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) response among lesions in bone-dominant metastatic breast cancer patients treated with systemic therapies. PATIENTS AND METHODS The metabolic response was analysed by comparing PET/CT scans carried out before and during a new treatment phase (n=46) in 25 bone-dominant metastatic breast cancer patients. Patients presented both bone and extra-bone metastases in 48% treatment phases. The metabolic response was analysed according to European Organization for Research and Treatment of Cancer (EORTC) criteria. A heterogeneous response was defined as the coexistence of responding and non-responding lesions within the same patient. RESULTS The lesion-based response analysis showed a heterogeneous metabolic response in 48% of treatment phases. In the subset with both bone and extra-bone metastases (n=20), PET/CT showed discordant responses between bone and extra-bone metastases in 6/20 (30%) treatment phases. Considering all the cases included in the study, the time to progression (TTP) was longer in cases with a metabolic response compared with the cases with a metabolic non-response (P=0.02). In cases with a PET/CT non-response, TTP seemed to be lower in those with a homogeneous non-response compared with those with a heterogeneous metabolic response (P=0.07). CONCLUSION Whole-body FDG-PET allows frequent heterogeneous responses after systemic therapy to be identified in bone-dominant metastatic breast cancer patients.

Progress in magnetic resonance imaging of brain tumours.

Purpose of review Advances in magnetic resonance based techniques have yielded improvements in both high-resolution anatomical imaging and methods to evaluate physiology and function. This review focuses on recent developments in these techniques as applied to pretreatment staging and post-treatment evaluation of brain tumours. Recent findings High-resolution spectroscopic imaging may contribute to pre-therapeutic grading and characterization of gliomas, as can diffusion techniques. The latter also hold promise in predicting survival in malignant supratentorial astrocytoma and could help to define areas for biopsy. Both methods can differentiate recurrent tumour from radiation injury. Perfusion-weighted magnetic resonance techniques offer potential markers of tumour angiogenesis and capillary permeability, and correlate well with vascular endothelial growth factor expression in grade II and grade III tumours. Functional magnetic resonance imaging can assess whether surgical treatment is feasible and select patients for intraoperative cortical stimulation. Combining multiple parameters in a magnetic resonance based diagnostic strategy could improve overall performance. Summary Magnetic resonance imaging provides insights into the physiology of human tumours in a way that is both noninvasive and radiation free. We may expect from these new imaging methods greater specificity in diagnosis and useful tools with which to predict and assess response to therapy.

MRI-Targeted Biopsies versus Systematic Transrectal Ultrasound Guided Biopsies for the Diagnosis of Localized Prostate Cancer in Biopsy Naïve Men

Introduction. To compare, in the same cohort of men, the detection of clinically significant disease in standard (STD) cores versus multiparametric magnetic resonance imaging (mpMRI) targeted (TAR) cores. Material and Methods. A prospective study was conducted on 129 biopsy naïve men with clinical suspicion of prostate cancer. These patients underwent prebiopsy mpMRI with STD systematic biopsies and TAR biopsies when lesions were found. The agreement between the TAR and the STD protocols was measured using Cohens kappa coefficient. Results. Cancer detection rate of MRI-targeted biopsy was 62.7%. TAR protocol demonstrated higher detection rate of clinically significant disease compared to STD protocol. The proportion of cores positive for clinically significant cancer in TAR cores was 28.9% versus 9.8% for STD cores (P < 0.001). The proportion of men with clinically significant cancer and the proportion of men with Gleason score 7 were higher with the TAR protocol than with the STD protocol (P = 0.003; P = 0.0008, resp.). Conclusion. mpMRI improved clinically significant prostate cancer detection rate compared to STD protocol alone with less tissue sampling and higher Gleason score. Further development in imaging as well as multicentre studies using the START recommendation is needed to elucidate the role of mpMRI targeted biopsy in the management of prostate cancer.

A prospective clinical trial of HIFU hemiablation for clinically localized prostate cancer

Background:Focal therapy is an emerging mini-invasive treatment modality for localized prostate cancer aimed to reduce the morbidity associated with radical therapy while maintaining optimal cancer control. We report the mid-term oncological and functional results of primary hemiablation high-intensity focused ultrasound (HIFU) in a prospective cohort of patients.Methods:Over 8 years, hemiablation HIFU was primarily performed in 50 selected patients with biopsy-proven clinically localized unilateral, low–intermediate risk prostate cancer in complete concordance with the prostate cancer lesions identified by magnetic resonance imaging with precise loci matching on multimodal approach. Post-treatment follow-up included regular serial PSA measurements. Biochemical recurrence was reported using Stuttgart and Phoenix criteria. The latter was used as a threshold to offer whole-gland biopsies.Results:Complete follow-up was available for all patients and the median follow-up was 39.5 months (range: 6–94). Mean nadir PSA value was 1.6 ng ml−1, which represents 72% reduction compared with initial PSA pre-treatment value (P<0.001). Median time to achieve PSA nadir was 3 months. Biochemical recurrence, according to Phoenix and Stuttgart definition, occurred in 28 and 36% of patients, respectively. The 5-year actuarial metastases-free survival, cancer-specific survival and overall survival rates were 93, 100 and 87%, respectively. Out of the eight patients undergoing biopsy, six patients had a positive biopsy for cancer occurring in the untreated contralateral (n=3) or treated ipsilateral lobe (n=1) or bilaterally (n=2). A Clavien–Dindo grade 3b complication occurred in two patients. Complete continence (no pads) and erection sufficient for intercourse were documented in 94 or 80% of patients, respectively.Conclusion:Hemiablation HIFU therapy, delivered with intention to treat, for carefully selected patients affords mid-term promising functional and oncological outcomes. The effectiveness of this technique should be now compared with whole-gland radical therapy.

Non-traumatic myositis ossificans in the paraspinal muscles

Myositis ossificans circumscripta (MOC) is a benign condition of heterotopic bone formation that remains difficult to distinguish from soft-tissue and bone malignancies. We describe an unusual case of non-traumatic MOC in the cervical paraspinal muscle. The diagnosis could only be established after surgery and histological examination. We present a review of the literature on this subject and discuss some related features (radiological and histological).

Primary Zonal High Intensity Focused Ultrasound for Prostate Cancer: Results of a Prospective Phase IIa Feasibility Study

Aims. In this study we report our results with storage of cryopreserved semen intended for preservation and subsequent infertility treatment in men with testicular cancer during the last 18 years. Methods. Cryopreserved semen of 523 men with testicular cancer was collected between October 1995 and the end of December 2012. Semen of 34 men (6.5%) was used for fertilization of their partners. They underwent 57 treatment cycles with cryopreserved, fresh, and/or donor sperm. Results. A total of 557 men have decided to freeze their semen before cancer treatment. Seminoma was diagnosed in 283 men (54.1%) and nonseminomatous germ cell tumors in 240 men (45.9%). 34 patients who returned for infertility treatment underwent 46 treatment cycles with cryopreserved sperm. Totally 16 pregnancies were achieved, that is, 34.8% pregnancy rate. Conclusion. The testicular cancer survivors have a good chance of fathering a child by using sperm cryopreserved prior to the oncology treatment, even when it contains only limited number of spermatozoa.

Quantitative DCE-MRI for prediction of pathological complete response following neoadjuvant treatment for locally advanced breast cancer: the impact of breast cancer subtypes on the diagnostic accuracy

ObjectivesTo assess whether DCE-MRI pharmacokinetic (PK) parameters obtained before and during chemotherapy can predict pathological complete response (pCR) differently for different breast cancer groups.MethodsEighty-four patients who received neoadjuvant chemotherapy for locally advanced breast cancer were retrospectively included. All patients underwent two DCE-MRI examinations, one before (EX1) and one during treatment (EX2). Tumours were classified into different breast cancer groups, namely triple negative (TNBC), HER2+ and ER+/HER2−, and compared with the whole population (WP). PK parameters Ktrans and Ve were extracted using a two-compartment Tofts model.ResultsAt EX1, Ktrans predicted pCR for WP and TNBC. At EX2, maximum diameter (Dmax) predicted pCR for WP and ER+/HER2−. Both PK parameters predicted pCR in WP and TNBC and only Ktrans for the HER2+. pCR was predicted from relative difference (EX1 − EX2)/EX1 of Dmax and both PK parameters in the WP group and only for Ve in the TNBC group. No PK parameter could predict response for ER+/HER−. ROC comparison between WP and breast cancer groups showed higher but not statistically significant values for TNBC for the prediction of pCRConclusionsQuantitative DCE-MRI can better predict pCR after neoadjuvant treatment for TNBC but not for the ER+/HER2− group.Key Points• DCE-MRI-derived pharmacokinetic parameters can predict response status of neoadjuvant chemotherapy treatment.• Ktrans can better predict pCR for the triple negative group.• No pharmacokinetic parameter could predict response for the ER+/HER2− group.

Cardiac assessment of early breast cancer patients 18 years after treatment with cyclophosphamide-, methotrexate-, fluorouracil- or epirubicin-based chemotherapy.

BACKGROUND Epirubicin-based chemotherapy improves the outcome of early breast cancer (BC) patients. However, cardiotoxicity remains an important side effect. METHODS We re-consented node-positive BC patients enrolled in a phase III trial between 1988 and 1996 which compared six cycles of oral cyclophosphamide, methotrexate, fluorouracil (CMF) versus two epirubicin-cyclophosphamide regimens differing by the anthracycline cumulative dose [standard-dose epirubicin and cyclophosphamide (SDE) (8 × 60 mg/m(2)) and higher-dose epirubicin and cyclophosphamide (HDE) (8 × 100 mg/m(2))]. Eligible patients were those who were alive and free of disease and had no contra-indications to the proposed tests (cardiac evaluation). Cardiotoxicity was defined as asymptomatic systolic dysfunction (left ventricular ejection fraction (LVEF)< 50%, New York Heart Association (NYHA) Class I) or symptomatic heart failure (NYHA Class II-IV). Differences in cardiotoxicity between CMF and SDE/HDE were assessed using chi-square and Fisher Exact tests for binary variables and t-test and Wilcoxon test for continuous variables. RESULTS Among the 777 patients, 20 cases of CHF were reported (CMF = 1, SDE = 5, HDE = 14; p < 0.001). Between September 2010 and June 2013, 82 patients (30%) out of 269 eligible patients accepted to participate in this substudy. Median follow-up was 18 years (range 15-24). Epirubicin-treated patients had significantly higher heart rate, more abnormal echocardiograms and LVEF by magnetic resonance imaging (MRI) compared to CMF-treated ones. A trend towards higher BNP was also observed in the SDE/HDE group (P = 0.08). No differences were observed in LVEF assessed by echocardiogram or troponin T levels. CONCLUSIONS Participation rate in this substudy was lower than expected highlighting the complexity of re-calling patients several years after the initial BC diagnosis. After 18 years, epirubicin-treated patients had a lower LVEF by MRI, more abnormal echocardiograms, higher heart rates compared to patients treated with CMF. However, no major delayed cardiotoxicity was observed.

Phase I trial combining temozolomide plus lapatinib for the treatment of brain metastases in patients with HER2-positive metastatic breast cancer: the LAPTEM trial

BACKGROUND Brain metastases (BMs) pose a clinical challenge in breast cancer (BC). Lapatinib or temozolomide showed activity in BM. Our study assessed the combination of both drugs as treatment for patients with HER2-positive BC and BM. METHODS Eighteen patients were enrolled, with sixteen of them having recurrent or progressive BM. Any type of previous therapy was allowed, and disease was assessed by gadolinium (Gd)-enhanced magnetic resonance imaging (MRI). The primary end points were the evaluation of the dose-limiting toxicities (DLTs) and the determination of the maximum-tolerated dose (MTD). The secondary end points included objective response rate, clinical benefit and duration of response. RESULTS The lapatinib-temozolomide regimen showed a favorable toxicity profile because the MTD could not be reached. The most common adverse events (AEs) were fatigue, diarrhea and constipation. Disease stabilization was achieved in 10 out of 15 assessable patients. The estimated median survival time for the 16 patients with BM reached 10.94 months (95% CI: 1.09-20.79), whereas the median progression-free survival time was 2.60 months [95% confidence interval (CI): 1.82-3.37]. CONCLUSIONS The lapatinib-temozolomide combination is well tolerated. Preliminary evidence of clinical activity was observed in a heavily pretreated population, as indicated by the volumetric reductions occurring in brain lesions.