Le Tourneau C., Dreno B., Kirova Y., Grob J. J., Jouary T., Dutriaux C., Thomas L., Lebbe C., Mortier L., Saiag P., Avril M. F., Maubec E., Bey P., Cosset J. M., Sun J. S., Asselain B., Devun F., Marty M. E., Dutreix M.
First-in-human phase I study of the DNA repair inhibitor DT01 in combination with radiotherapy in patients with in transit melanoma.
J. Clin. Oncol..
Le Rhun E., Mateus C., Mortier L., Dhermain F., Guillot B., Grob J. J., Lebbe C., Thomas M., Jouary T., Leccia M. T., Robert C.
Systemic treatment of melanoma brain metastases.
Melanomas have a high rate of brain metastases. Both the functional prognosis and the overall survival are poor in these patients. Until now, surgery and radiotherapy represented the two main modalities of treatment. Nevertheless, due to the improvement in the management of the extracerebral melanoma, the systemic treatment may be an option in patients with brain metastases. Immunotherapy with anti-CTLA4 (cytotoxic T-lymphocyte-associated protein 4) - ipilimumab - or BRAF (serine/threonine-protein kinase B-raf) inhibitors - vemurafenib, dabrafenib - has shown efficacy in the management of brain metastases in a- or pauci-symptomatic patients. Studies are ongoing with anti-PD1 (programmed cell death 1) and combinations of targeted therapies associating anti-RAF (raf proto-oncogene, serine/threonine kinase) and anti-MEK (mitogen-activated protein kinase kinase).
Le Rhun E., Dhermain F., Noel G., Reyns N., Carpentier A., Mandonnet E., Taillibert S., Metellus P.
ANOCEF guidelines for the management of brain metastases.
The incidence of brain metastases is increasing because of the use of new therapeutic agents, which allow an improvement of overall survival, but with only a poor penetration into the central nervous system brain barriers. The management of brain metastases has changed due to a better knowledge of immunohistochemical data and molecular biological data, the development of new surgical, radiotherapeutic approaches and improvement of systemic treatments. Most of the time, the prognosis is still limited to several months, nevertheless, prolonged survival may be now observed in some sub-groups of patients. The main prognostic factors include the type and subtype of the primitive, age, general status of the patient, number and location of brain metastases, extracerebral disease. The multidisciplinary discussion should take into account all of these parameters. We should notice also that treatments including surgery or radiotherapy may be proposed in a symptomatic goal in advanced phases of the disease underlying the multidisciplinary approach until late in the evolution of the disease. This article reports on the ANOCEF (French neuro-oncology association) guidelines. The management of brain metastases of breast cancers and lung cancers are discussed in the same chapter, while the management of melanoma brain metastases is reported in a separate chapter due to different responses to the brain radiotherapy.
Le Nobin J., Rosenkrantz A. B., Villers A., Orczyk C., Deng F. M., Melamed J., Mikheev A., Rusinek H., Taneja S. S.
Image Guided Focal Therapy for Magnetic Resonance Imaging Visible Prostate Cancer: Defining a 3-Dimensional Treatment Margin Based on Magnetic Resonance Imaging Histology Co-Registration Analysis.
PURPOSE: We compared prostate tumor boundaries on magnetic resonance imaging and radical prostatectomy histological assessment using detailed software assisted co-registration to define an optimal treatment margin for achieving complete tumor destruction during image guided focal ablation. MATERIALS AND METHODS: Included in study were 33 patients who underwent 3 Tesla magnetic resonance imaging before radical prostatectomy. A radiologist traced lesion borders on magnetic resonance imaging and assigned a suspicion score of 2 to 5. Three-dimensional reconstructions were created from high resolution digitalized slides of radical prostatectomy specimens and co-registered to imaging using advanced software. Tumors were compared between histology and imaging by the Hausdorff distance and stratified by the magnetic resonance imaging suspicion score, Gleason score and lesion diameter. Cylindrical volume estimates of treatment effects were used to define the optimal treatment margin. RESULTS: Three-dimensional software based registration with magnetic resonance imaging was done in 46 histologically confirmed cancers. Imaging underestimated tumor size with a maximal discrepancy between imaging and histological boundaries for a given tumor of an average +/- SD of 1.99 +/- 3.1 mm, representing 18.5% of the diameter on imaging. Boundary underestimation was larger for lesions with an imaging suspicion score 4 or greater (mean 3.49 +/- 2.1 mm, p <0.001) and a Gleason score of 7 or greater (mean 2.48 +/- 2.8 mm, p = 0.035). A simulated cylindrical treatment volume based on the imaging boundary missed an average 14.8% of tumor volume compared to that based on the histological boundary. A simulated treatment volume based on a 9 mm treatment margin achieved complete histological tumor destruction in 100% of patients. CONCLUSIONS: Magnetic resonance imaging underestimates histologically determined tumor boundaries, especially for lesions with a high imaging suspicion score and a high Gleason score. A 9 mm treatment margin around a lesion visible on magnetic resonance imaging would consistently ensure treatment of the entire histological tumor volume during focal ablative therapy.
Kramkimel N., Thomas-Schoemann A., Sakji L., Golmard J. L., Noe G., Maubec E., Vidal M., Avril M. F., Mortier L., Goldwasser F., Dupin N., Blanchet B.
Relationships between vemurafenib exposure and safety and efficacy in outpatients with BRAF-mutated melanoma.
Fundam. Clin. Pharmacol..
Kraeber-Bodere F., Bodet-Milin C., Berriolo-riedinger A., Devaux J. Y., Huglo D., Giammarile F., Dupas B., Nguyen J. M., Attal M., Moreau P.
FDG PET/CT and MRI in multiple myeloma patients: preliminary results of the IMAJEM study.
J. Nucl. Med..
Khodari M., Ouzzane A., Marcelli F., Yakoubi R., Mitchell V., Zerbib P., Rigot J. M.
Azoospermia and a history of inguinal hernia repair in adult.
BACKGROUND: Inguinal hernia repair is one of the most performed surgeries in the world. It is recognized that any surgery of the pelvic floor may represent a risk factor of male infertility. METHOD: Retrospective study of patients with azoospermia and a history of adult inguinal hernia repair surgery and referred to our center between January 1990 and January 2011 for infertility. RESULTS: Among 69 azoospermia patients with history of adult inguinal hernia repair surgery, 60 patients underwent surgical extraction of sperm that was successful in 75% (45/60). Positive extraction rate decreases in the subgroup of patients with risk factors for infertility (61.4%) as well as in the group with bilateral inguinal hernia (67.9%). There was no statistically significant difference in the positive rate of sperm retrieval according to surgical technique or according to the use of polypropylene mesh (P>0.05). CONCLUSION: The obstruction of the vas deferens due to an inguinal hernia repair was a potential iatrogenic cause of male infertility that was rare and underestimated. The influence of using a polypropylene mesh was not clearly demonstrated. The management of these patients is based on prevention in order to identify patients with risk factors of infertility in order to propose a presurgery cryopreservation of sperm. LEVEL OF EVIDENCE: 5.
Jarraya H., Borde P., Mirabel X., Ernst O., Boulanger T., Lartigau E., Ceugnart L., Kramar A., Taieb S.
Lobulated Enhancement Evaluation in the Follow-Up of Liver Metastases Treated by Stereotactic Body Radiation Therapy.
Int. J. Radiat. Oncol. Biol. Phys..
OBJECTIVE: The Response Evaluation Criteria in Solid Tumors (RECIST) can have limitations when used to evaluate local treatments for cancer, especially for liver malignancies treated by stereotactic body radiation therapy (SBRT). The aim of this study was to validate the relationship between the occurrence of lobulated enhancement (LE) and local relapse and to evaluate the utility of this relationship for predicting local progression. PATIENTS AND METHODS: Imaging data of 59 lesions in 46 patients, including 281 computed tomographic (CT) scans, were retrospectively and blindly reviewed by 3 radiologists. One radiologist measured the lesion size, for each CT and overall, to classify responses using RECIST threshold criteria. The second studied LE occurrence. A third radiologist was later included and studied LE occurrence to evaluate the interobserver consistency for LE evaluation. RESULTS: The mean duration of follow-up was 13.6 months. LE was observed in 16 of 18 progressive lesions, occurring before size-based progression in 50% of cases, and the median delay of LE detection was 3.2 months. The sensitivity of LE to predict progression was 89%, and its specificity was 100%. The positive predictive value was 100%, the negative predictive value was 95.3%, and the overall accuracy was 97%. The probability of local progression-free survival at 12 months was significantly higher for lesions without LE compared with all lesions: 0.80 (CI 95%: 0.65-0.89) versus 0.69 (CI 95%: 0.54-0.80), respectively. The overall concordance rate between the 2 readers of LE was 97.9%. CONCLUSION: Response assessment of liver metastases treated by SBRT can be improved by including LE. This study demonstrates the diagnostic and predictive utility of LE for assessing local progression at a size still eligible for local salvage treatment.
Huret B., Perez T., Dhalluin X., Dewavrin F., Ramon P. P., Fournier C.
Treatment of malignant central airways obstruction by rigid bronchoscopy.
Rev. Mal. Respir..
INTRODUCTION: Endobronchial resection is now the standard treatment for tracheobronchial narrowing due to malignancy. The clinical and functional respiratory improvement has been evaluated previously but only in heterogeneous population. METHODS: Between February 2009 and February 2011, we conducted a prospective single centre study at the University Hospital of Lille. Twenty-five patients with malignant tracheobronchial stenosis received a clinical and functional respiratory evaluation before and after a rigid bronchoscopy procedure to reduce the obstruction followed where appropriate by placement of an endobronchial stent. RESULTS: Thirteen patients (52%) had primary lung cancer and in 12 the tumor had another origin. Nineteen patients (76%) received a stent after bronchial unblocking. Clinically, all patients felt an improvement in their dyspnea estimated by the Borg score with a median improvement of -2 points [-1; -4] following the procedure (P<0.001). In 96% the dyspnea visual analogic scale improved by 40 mm [27; 67] (P<0.0001). The FEV1 increased significantly after unblocking by 9% [-3.5; 28.5] (P<0.05). The Rint decreased significantly by -0.19 kPa/L per second [-0.06; -0.023] (P=0.001). Correlations between scales of dyspnea and spirometric values were not significant (P>0.05). The survival rate at 1 year was 29%. CONCLUSION: Interventional bronchoscopy decreases dyspnea. It modestly improves respiratory function and decreases the Rint. However, lung function and dyspnea scales are not correlated. No spirometry factor can predict clinical dyspnea response but an elevated Borg dyspnea scale might be a good indicator.