Activity and safety of afatinib in a window preoperative EORTC study in patients with squamous cell carcinoma of the head and neck (SCCHN).

Background: To investigate the activity and safety of afatinib in the preoperative treatment of squamous cell carcinoma of the head and neck (SCCHN). Patients and methods: This study was an open-label, randomized, multicenter, phase II window of opportunity trial. Treatment-naïve SCCHN patients selected for primary curative surgery were randomized (5 : 1 ratio) to receive afatinib during 14 days (day -15 until day -1) before surgery (day 0) or no treatment. Tumor biopsies, 2-[fluorine-18]-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET), and magnetic resonance imaging (MRI) were carried out at diagnosis and just before surgery. The primary end point was metabolic FDG-PET response (according to EORTC guidelines). Other end points included response assessment based on the Response Evaluation Criteria In Solid Tumors (RECIST) v1.1, dynamic contrast-enhanced (DCE)-MRI, diffusion weighted (DW)-MRI, safety, and translational research (TR). Results: Thirty patients were randomized: 25 to afatinib and 5 to control arm. Of the 23 eligible patients randomized to afatinib, 16 (70%; 95% CI: 47% to 87%) patients had a partial metabolic FDG-PET response (PMR). Five patients (22%; 95% CI: 8% to 44%) showed a partial response by RECISTv1.1. Responses assessed via DCE-MRI and DWI-MRI did not show a strong association with PMR or RECIST. One patient discontinued afatinib after 11 days for grade 3 diarrhea with subsequent renal failure and 24 days delay in surgery. No grade 4 toxicities or surgical comorbidities related to afatinib were reported. TR results indicated that PMR was more frequent in the tumors with high Cluster3-hypoxia score expression and with TP53 wild type. Conclusion: Afatinib given for 2 weeks to newly diagnosed SCCHN patients induces a high rate of FDG-PET partial metabolic response and partial response according to RECISTv1.1. Afatinib can be safely administered before surgery. Although exploratory, the hypoxic gene signature needs further investigations as a predictive biomarker of afatinib activity. Clinical trial registration: ClinicalTrials.gov: NCT01538381.

Are concurrent systematic cores needed at the time of targeted biopsy in patients with prior negative prostate biopsies?

INTRODUCTION AND OBJECTIVES: MRI-guided targeted biopsies are advised in patients who have undergone an initial series of negative systematic biopsies, in whom prostate cancer (PCa) suspicion remains elevated. The aim of the study was to evaluate whether, in men with prior negative prostate biopsies, systematic cores are also warranted at the time of an MRI-targeted repeat biopsy. MATERIAL AND METHODS: We enrolled patients with prior negative biopsy undergoing real time MRI/TRUS fusion guided prostate biopsy at our institute between 2014 and 2016. Patients with at least one index lesion on multiparametric MRI were included. All eligible patients underwent both systematic random biopsies (12-14 cores) and targeted biopsies (2-4 cores). RESULTS: The study included 74 men with a median age of 65 years, PSA level of 9.27ng/mL, and prostatic volume of 45ml. The overall PCa detection rate and the clinically significant cancer detection rate were 56.7% and 39.2%, respectively. Targeted cores demonstrated similar clinically significant PCa detection rate compared to systematic cores (33.8% vs. 28.4%, P=0.38) with significantly less tissue sampling. Indeed, a combination approach was significantly superior to a targeted-only in overall PCa detection (+16.7% overall detection rate, P=0.007). Although differences in clinically significant PCa detection were statistically non-significant (P=0.13), a combination approach did allow detecting 7 extra clinically significant PCas (+13.8%). CONCLUSIONS: In patients with elevated PSA and prior negative biopsies, concurrent systematic sampling may be needed at the time of targeted biopsy in order to maximize PCa detection rate. Larger studies are needed to validate our findings. LEVEL OF EVIDENCE: 4.

[Practical approach of lymphomas: major role of general practitioner who has to face all these emerging drugs]. / Approche pratique des lymphomes : rôle majeur du médecin généraliste face à l'explosion des nouvelles thérapeutiques.

Malignant lymphoma and other lymphoproliferative disorders represent a group of malignant hemopathies where immunotherapy has allowed spectacular progresses over the last ten years. The recent W.H.O. classification, based upon tumor immunology, and cytogenetical anomalies, allows a better identification of each lymphoma and the comparison of homogeneous populations within various clinical studies. The increase in the incidence of non-Hodgkin lymphoma is related to the aging of the population as well as to other factors that are still to be analysed - a real challenge for the future. We have tried to offer an overview of the latest therapeutical advances while focusing on the major role of general practitioner. The most frequency askeed questions will be discussed.

[Cardiac metastase of a soft tissue sarcoma: a case report and a review of the literature]. / Métastase cardiaque d'un sarcome des tissus mous: cas clinique et revue de la literature.

Soft tissue sarcomas represent rare tumors. They recur most often locally and in the lungs. We report the case of a 58-year woman who was treated for awith chemotherapy and then surgery. About a year after the end of the treatment an intracardiac mass was identified during a follow up chest CT-scan. The patient underwent a surgical resection of that mass found to bel myxoid chondrosarcoma metastasis. Only 2 cases of cardiac dissemination of extraskeletal myxoid chondrosarcoma have been described. The differential diagnosis of intracardiac masses is discussed. In some carefully selected cases atrisks of obstructive shock or embolization and unique metastatic location, cardiac surgery should be considered.

Improved diagnostic accuracy of readout-segmented echo-planar imaging for peripheral zone clinically significant prostate cancer: a retrospective 3T MRI study.

This study compares the readout-segmented echo-planar imaging (rsEPI) from the conventional single-shot EPI (ssEPI) diffusion-weighted imaging (DWI) for the discrimination of patients with clinically significant prostate cancer (csPCa) within the peripheral zone (PZ) using apparent diffusion coefficient (ADC) maps and pathology report from magnetic resonance imaging (MRI)-targeted biopsy. We queried a retrospective monocentric database of patients with targeted biopsy. csPCa patients were defined as an International Society of Urological Pathology grade group ≥ 2. Group-level analyses and diagnostic accuracy of mean ADC values (ADCmean) within the tumor volume were assessed from Kruskal-Wallis tests and receiving operating characteristic curves, respectively. Areas under the curve (AUC) and optimal cut-off values were calculated. 159 patients (105 rsEPI, 54 ssEPI; mean age ± standard deviation: 65 ± 8 years) with 3T DWI, PZ lesions and targeted biopsy were selected. Both DWI sequences showed significantly lower ADCmean values for patients with csPCa. The rsEPI sequence better discriminates patients with csPCa (AUCrsEPI = 0.84, AUCssEPI = 0.68, p < 0.05) with an optimal cut-off value of 1232 µm2/s associated with a sensitivity-specificity of 97%-63%. Our study showed that the rsEPI DWI sequence enhances the discrimination of patients with csPCa.

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.

[Non Hodgkin's lymphomas: a major breakthrough with immunotherapy]. / Les lymphomes non hodgkiniens: apports considérables de i'immunothérapie.

Non hodgkin's lymphomas are a group of haematological malignancies in which spectacular progress has been made over the last ten years thanks to immunotherapy. Furthermore, the new WHO classification, based upon tumour immunology, the degree of tumour differentiation and cytogenetic abnormalities, has finally improved identification of each lymphoma and has enabled comparison of homogeneous populations between different clinical studies. The increase in the incidence of non hodgkin's lymphoma is related to the aging of the population and to other factors that are yet to be elucidated--a real challenge for the future. We have tried to offer an overview of the latest therapeutic advances, with a focus on (radio-) immunotherapy and haemopoietic stem cell transplantation.

[Thyroid cancers]. / Les cancers thyroïdiens.

During the last two decades, the incidence of thyroid cancer has doubled, mainly do to the early detection of small papillary tumors. However, mortality stayed stable (0.05/100.000). Well differentiated cancers (papillary and follicular) demonstrated a excellent survival prognosis (95 % at 30 years for the majority of the patients), factors of prognosis: age, size of the initial tumor, presence (or not) of distant metastases, lymph node involvement (only in patients 45 year or older). Surgery is the main treatment and should be with curative intent, hence the importance of a thorough preoperative work-up: sonography, needle aspiration cytology and MRI of cervicomediastinum for large tumors and/or suspected lymph nodes. Total thyroidectomy is mandatory, excepted for well selected patients with small (pT1) unilateral tumors under the age of 45. Central compartment lymph node clearance is advocated (but not evidence based) with presentation of the recurrent laryngeal nerves and of the parathyroids. Ablation of residual thyroid tissue (Iode 131) should be advocated for patients at high (or intermediary) risk of recurrence, only after multidisciplinary concertation. Unlimited follow-up checking the thyroglobulin serum local after the total thyroidectomy and radioactive ablation, the availability of recombinant rhTSH avoids the withdrawal of thyroid hormones (hypothyroid period). Anaplastic carcinomas are very aggressive, no therapeutic solution, excepted in some selected case for when radical surgery is possible (flap reconstruction) followed by chemoradiation. Calcitoninenia to detect and to follow medullary thyroid cancer after total thyroidectomy and lymph node clearance.

[Interest of the chest CT scanning in head and neck cancer]. / Intérêt du scanner thoracique dans le bilan initial et le suivi des patients traités pour un cancer des voies aérodigestives supérieures.

INTRODUCTION: The overall survival rate for patients with head and neck squamous cell carcinoma remains disappointingly static despite improved locoregional control. This has been attributed to the development of distant metastases and second primary malignancies in these patients, a large proportion of which occur in the thorax. The goal of this study is to determine the incidence of newly thoracic malignancies diagnosed initially and during the follow-up in head and neck patients by chest computed tomography. METHODS: We retrospectively analysed the incidence of thoracic malignancies in 77 patients presented newly diagnosed cancer of the head and neck. RESULT: 15/77 patients were found to have thoracic malignancies. In 10/77 patients (14%) the diagnosis was made at the same time that the initial head and neck cancer In 5/77 patients, the thoracic malignancies were diagnosed during the follow-up. In 3 of the 5 cases, the pulmonary lesion was diagnosed in patients with local recurrent tumours. The primary site or the stage had an effect on the incidence of simultaneous thoracic malignancies. CONCLUSION: The presence of distant metastases and second primary malignancies has major implications in the management and prognosis of patients presenting with head and neck carcinoma. We recommend a CT scanning of the thorax in the staging of patients presenting with head and neck cancer but also in the follow-up, particularly in patients with an advanced pharyngolaryngeal cancer.

Sentinel lymph node evaluation in squamous cell carcinoma of the head and neck cancer: preliminary results.

INTRODUCTION: Sentinel lymph node biopsy is a new technique in staging the clinically NO neck. Tumour spread to the neck is the most important prognostic factor in head and neck squamous cell carcinoma (HNSCC). MATERIAL AND METHODS: Patients with histologically confirmed HNSCC, with no clinical and no radiological (CT or MRI) evidence of cervical lymph node involvement were eligible for this prospective study. The lymph node mapping was performed by preoperative lymphoscintigraphy and intraoperative use of hand-held gamma probe. Four injections (with Tc 99m-labeled nanocolloids) were performed around the primary tumour. The SLN, as indicated by dynamic scintigraphy and the neck dissection specimen, were sent separately for histological analysis. The presence of occult metastasis in the SLN and in the neck dissection specimen were compared. RESULTS: Ten consecutive patients (8 males ; 2 females) with a mean age of 61 years (range 47 to 74 years) were prospectively entered into the study. The primary tumour was located on the oral tongue in 4 cases, in the floor of the mouth in 5 cases and in the oropharynx in 1 case. Primary tumours were staged T2 in nine cases, one tumour was staged T1 according to UICC 1997. All the tumours were clinically staged cN0 by palpation and computed tomography (or MRI). Lymphoscintigraphy was performed and revealed a SLN in all cases. The sentinel node biopsy technique permitted an upstaging of the clinically cN0 neck in 3/10 cases. The SLN technique was false negative in one patient with a skip metastasis. CONCLUSION: SLN evaluation in HNSCC is feasible and provides a highly accurate staging of NO necks in oral and oropharyngeal carcinomas.

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.

Acute respiratory failure from tracheopathia osteoplastica.

Tracheopathia osteoplastica is a benign cartilaginous and osseous metaplasia of the laryngo-tracheobronchial tree diagnosed more commonly in adults over 50 years of age. We report here the case of a 54-year-old man who underwent thyroidectomy for multinodular goiter. Immediately after an uneventful surgery, he developed an acute respiratory failure with radiologic picture of Adult Respiratory Distress Syndrome. Mechanical ventilation was set up again, bronchoscopy with biopsy disclosed a massive tracheobronchial haemorrhage from a tracheopathia osteoplastica. Supportive treatment was successfully provided and the patient resumed to a normal life 14 days after the operation.

Acute respiratory failure from tracheopathia osteoplastica.

Tracheopathia osteoplastica is a benign cartilaginous and osseous metaplasia of the laryngo-tracheobronchial tree diagnosed more commonly in adults over 50 years of age. We report here the case of a 54-year-old man who underwent thyroidectomy for multinodular goiter. Immediately after an uneventful surgery, he developed an acute respiratory failure with radiologic picture of Adult Respiratory Distress Syndrome. Mechanical ventilation was set up again, bronchoscopy with biopsy disclosed a massive tracheobronchial haemorrhage from a tracheopathia osteoplastica. Supportive treatment was successfully provided and the patient resumed to a normal life 14 days after the operation.

Diagnosis of Cholecysto-Colonic Fistula Using Gadoxetic Acid - Magnetic Resonance Cholangiography.

We report the demonstration (for the first time to our knowledge) of a cholecysto-colonic fistula using Primovist® enhanced MRCP in a 74-year-old patient. We discuss the advantage of this newly emerged technique over traditional T2-weighted MRCP in this indication.

Neoadjuvant chemotherapy with cisplatin, methotrexate, bleomycin and vincristine (CABO) in patients with stage III and IV squamous cell carcinoma of the head and neck.

Forty-six patients with Stage III-IV previously untreated squamous cell carcinoma of the head and neck were treated with neoadjuvant chemotherapy with cisplatin, methotrexate, bleomycin and vincristine. The overall response rate was 70%, with a 9% complete response rate. The most frequent side effects were myelosuppression, nausea and vomiting, alopecia, neurotoxicity and stomatitis. Definitive local therapy consisted of surgery alone in 13 cases, surgery plus radiation in another 13, and radiotherapy alone in 14. Six patients, four of whom died, received no definitive local therapy and two were lost to follow-up. The median disease-free survival time was 10.5 months, and the most frequent cause of failure was local regional relapse (85%). Median survival time was 13 months and there were eight long-term survivals (median 48 months). Response to chemotherapy was independent of all analysed prognostic factors. Disease-free survival and survival were significantly influenced by the presence or absence of lymph nodes. Our results do not support the routine use of neoadjuvant chemotherapy with cisplatin, methotrexate, bleomycin, and vincristine in patients with advanced cell carcinoma of the head and neck.

Invited review: biophysical properties and clinical applications of magnetic resonance imaging contrast agents.

Contrast enhanced magnetic resonance imaging (MRI) is a very versatile and effective technique for detecting and characterizing lesions, for identifying a variety of patho-physiological abnormalities, and for providing perfusion and functional information. The application of contrast enhanced MRI to many clinical and research indications has emerged because of the rapid evolution in imaging techniques, improved methodology, and the development of efficient and specific contrast agents. Problems related to optimizing parameters and dosage have been due to complex interplay of relaxation times, biophysical mechanisms and acquisition parameters. A knowledge of basic biophysical aspects is therefore essential for a full understanding of the results obtained for different organs under different conditions, and for optimizing the image parameters and dosage of contrast agents. This article underlines the biophysical basis of the effects of contrast agents in MRI, identifies the problems involved in optimizing the parameters for maximum efficiency, and presents a general overview of the clinical studies and research applications in the central nervous system, perfusion abnormalities, hepatobiliary system, musculoskeletal system and the gastrointestinal tract. The section on perfusion studies includes a discussion of quantitative analysis and kinetic models describing the effects of contrast agents. Finally, a critical evaluation of the scope and limitations of contrast enhanced MRI is presented.

Vidian metastasis of adenoid cystic carcinoma.

Head and neck tumors may invade perineural space, especially the maxillary division of the trigeminal nerve and the pterygopalatine fossa (PPF). Computed tomography (CT) and magnetic resonance imaging (MRI) signs of perineural extension include essentially the obliteration of the PPF fatty content and the enlargement and erosion of neural foramina. We report a case of perividian metastasis studied with CT and MRI.

[Occipitalization of the ventral part and vertebralization of the dorsal part of the atlas]. / Occipitalisation de la partie ventrale et vertébralisation de la partie dorsale de l'atlas.

The authors report a second case of an original malformation of the atlas vertebra which consists in occipitalization of the anterior and lateral parts (anterior hemi-arch) and in vertebralization of the posterior parts (posterior hemi-arch).

[Magnetic resonance imaging of the pituitary gland and the sella turcica region. Normal and pathological aspect]. / Imagerie par résonance magnétique de l'hypophyse et la région parasellaire. Aspect normal et pathologique.

MRI may be presently considered as the optimal imaging technique for the study of the sellar and parasellar region. Excellent anatomic and multiplanar approach, absence of irradiation, spontaneous visualization of vascular elements, absence of artefacts characterize MRI. The normal aspect of the sellar region is first described on both spin-echo, T1 and T2 weighted images. MRI appearance of micro and macroadenomas is described. The use of paramagnetic contrast agents (Gadolinium DTPA or DOTA) is widely accepted as a useful complementary diagnostic tool. Moreover the most commonly encountered lesions of the sellar region are reviewed and their behaviour on MRI discussed. Although MRI is an outstanding imaging technique, particularly useful for the study of the sellar region it must be stressed that MRI lacks of specificity. As a consequence, it is of utmost importance to compare MRI with clinical and biological examinations in order to reach a confident final diagnosis.

[How can metastatic extension be assessed in the brain?]. / Comment évaluer l'extension métastatique au niveau cérébral?

MRI is the technique of choice to detect cerebral metastases. Double-dose delayed CT is the optimal CT examination to be performed in case of limited access to MRI. If the examination shows the presence of multiple metastases, MRI is not necessary. If CT shows an apparently single lesion, an MRI examination is essential, considering the number of lesions detected by MRI and not seen with CT.