[Concomitant radiotherapy and trastuzumab: Rational and clinical implications]. / Association radiothérapie et trastuzumab : rationnel et implications cliniques.

The HER2 receptor (Human Epidermal Growth Receptor 2) is a transmembrane receptor with tyrosine kinase activity that is over-expressed in 25-30 % of breast carcinomas. Its activation is associated with an exaggeration of cell proliferation with an increase in repair capacity resulting in increased radioresistance. On cardiac tissues, HER2 receptor activation plays a cardio-protective role. Trastuzumab, the first anti-HER2 drug used to treat patients with breast cancer overexpressing HER2 receptor , inhibits the cascade of reactions resulting in the proliferation of tumor cells, thus restoring cellular radiosensitivity. However, the combination of Trastuzumab with radiation therapy also removes HER2 receptor cardio-protective role on myocardial cells which increases the risk of cardiotoxicity. Thus, the concomitant association of these two modalities has long been a subject of controversy. Recent advances in radiation therapy technology and early detection of cardiac injury may limit the cardiotoxicity of this combination. Through this review, we developed the biological basis and the benefit-risk of concomitant combination of radiotherapy and Trastuzumab in adjuvant treatment of breast cancers overexpressing HER2 and we discuss the modalities of its optimization.

[Adaptive radiotherapy for nasopharyngeal carcinomas: Where are we?] / La radiothérapie adaptative des carcinomes nasopharyngés : où sommes-nous ?

Modern high-precision radiotherapy techniques have recently incorporated the notion of anatomical variations of the patient during treatment and have tried to adapt the treatment planning to them. Adaptive radiotherapy for nasopharyngeal tumors is starting to prove its benefit nowadays. His interest is constantly being evaluated. The variations encountered during the treatment are both geometric and dosimetric. They are represented by a reduction in the macroscopic tumors volume, a change in its position and a consequent dosimetric impact. The changes also concern organs at risk with a reduction of glandular structure volumes, and a different position which increases their doses. Delivered doses to noble structures (brainstem and spinal cord) may also increase. However, difficulties are encountered in its realization. There is a problem to perfectly reproduce the patient position during the second acquisition, which impacts the fusion quality between the two CT scans. This generates an imprecision in the definition of the same treatment isocentre on the second scanner. Also, there is a difficulty in accumulated doses calculation. The indication of adaptive radiotherapy remains a subject of controversy. It should be proposed for a subgroup of patients who could benefit from this new strategy. We present here an update on the state of the art of adaptive radiotherapy for nasopharyngeal cancer.

Dosimetric impact on changes in target volumes during intensity-modulated radiotherapy for nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To assess anatomic changes during intensity modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC) and to determine its dosimetric impact. PATIENTS AND METHODS: Twenty patients treated with IMRT for NPC were enrolled in this study. A second CT was performed at 38 Gy. Manual contouring of the macroscopic tumor volumes (GTV) and the planning target volumes (PTV) were done on the second CT. We recorded the volumes of the different structures, D98 %, the conformity, and the homogeneity indexes for each PTV. Volume percent changes were calculated. RESULTS: We observed a significant reduction in tumor volumes (58.56 % for the GTV N and 29.52 % for the GTV T). It was accompanied by a significant decrease in the D98 % for the 3 PTV (1.4 Gy for PTV H, p = 0.007; 0.3 Gy for PTV I, p = 0.03 and 1.15 Gy for PTV L, p = 0 0.0066). In addition, we observed a significant reduction in the conformity index in the order of 0.02 (p = 0.001) and 0.01 (p = 0.007) for PTV H and PTV I, respectively. The conformity variation was not significant for PTV L. Moreover, results showed a significant increase of the homogeneity index for PTV H (+ 0.03, p = 0.04) and PTV L (+ 0.04, p = 0.01). CONCLUSION: Tumor volume reduction during the IMRT of NPC was accompanied by deterioration of the dosimetric coverage for the different target volumes. It is essential that a careful adaptation of the treatment plan be considered during therapy for selected patients.

3D segmentation of nasopharyngeal carcinoma from CT images using cascade deep learning.

In the paper, we propose a new deep learning-based method for segmenting nasopharyngeal carcinoma (NPC) in the nasopharynx from three orthogonal CT images. The proposed method introduces a cascade strategy composed of two-phase manners. In CT images, there are organs, called non-target organs, which NPC never invades. Therefore, the first phase is to detect and eliminate non-target organ regions from the CT images. In the second phase, NPC is extracted from the remained regions in the CT images. Convolutional neural networks (CNNs) are applied to detect non-target organs and NPCs. The proposed system determines the final NPC segmentation by integrating three results obtained from coronal, axial and sagittal images. Moreover, we construct two CNN-based NPC detection systems using one kind of overlapping patches with a fixed size and various overlapping patches with different sizes. From the experiments using CT images of 70 NPC patients, our proposed systems, especially the system using various patches, achieves the best performance for detecting NPC compared with conventional NPC detection methods.

[Neoadjuvant chemotherapy with concurrent chemoradiotherapy in the treatment of nasopharyngeal cancer: Southern Tunisian experience]. / La chimiothérapie néoadjuvante associée à la chimioradiothérapie concomitante dans le traitement du cancer du nasopharynx : expérience du Sud-Tunisien.

PURPOSE: A retrospective study to evaluate the efficacy and safety of the addition of neoadjuvant chemotherapy to concurrent chemoradiotherapy in the treatment of nasopharyngeal carcinoma. PATIENTS AND METHODS: Data from 62 patients treated for non-metastatic nasopharyngeal carcinoma were analyzed by comparing two groups of patients: a first group of 32 patients treated with 3 cycles of neoadjuvant chemotherapy based on docetaxel, cisplatin and 5-fluoro-uracil every 21 days followed by concurrent chemoradiotherapy (weekly cisplatin 40mg/m2 with radiotherapy 70Gy, 2Gy per session, 5 sessions per week) and a second group of 30 patients treated with the same concurrent chemoradiotherapy. RESULTS: After a median follow-up of 53.5 months, neoadjuvant chemotherapy showed a significant reduction in the rate of a distant metastatic relapses (3.3% vs. 10%, P=0.03). No significant difference in disease-free survival at 5 years (65.6% vs. 68.8%, P=0.46) or overall survival at 5 years (68.8% vs. 73.3%, P=0.46) was noted between the two groups. Induction chemotherapy was associated with febrile neutropenia of 15.6%. During concurrent chemoradiotherapy, hematological complications were greater in the first chemotherapy group (53% vs. 33%). CONCLUSION: Induction chemotherapy by docetaxel, cisplatin and 5-fluoro-uracil is a safe and effective option in the treatment of nasopharyngeal carcinoma. A better definition of high risk of relapse group would optimize the indications of this chemotherapy in the therapeutic arsenal.

A Comparative Study of Breast Cancer Screening by Age Across 10000 Tunisian Women.

INTRODUCTION: We propose in this study to analyze the results obtained in the experience of Dar El Amal by comparing the two age groups 45-49 years versus over 50 years. This experience of Dar Al Amal was started in Sfax (Tunisia) in 2004. The project had included women over a period of six and a half years. The target population was all women over the age of 45 years. RESULTS: In the period of the study, 10 000 women had at least one mammography within the first round in Dar El Amal. The average age was 51.56 years. The recall rate was more important in women aged 45-49 years compared with those over 50 years with a statistically significant relationship (p=0.013). Tests classified ACR0 and ACR3 predominated in women aged between 45 and 49 years with a statistically significant relationship. The positive predictive value (PPV) of mammography was better in those over 50 years (p=0.012). CONCLUSION: The majority of countries in the world opt for screening from the age of 50 years. Women under 50 years are not routinely concerned, but they have more right to a targeted and appropriate screening.

PIK3CA amplification is predictive of poor prognosis in Tunisian patients with nasopharyngeal carcinoma.

PI3Ks (phosphatidylinositol 3-kinases) are lipid kinases that regulate signalling pathways involved in cell proliferation, motility, and adhesion. Somatic mutations and amplification of the PIK3CA gene have been reported in various types of human cancers. However, little is known about the frequency and prognosis role of PIK3CA activation in nasopharyngeal carcinoma (NPC). This study was conducted with the aim to screen for PIK3CA mutations in the two hot spot regions (exons 9 and 20) and to investigate for the PIK3CA gene amplification combined with the expression analysis of the phosphorylated Akt (pAkt). We showed that among 88 specimens, none had mutation in the helical domain (exon 9) and only one (1.13%) had mutation in the kinase domain (exon 20). On the other hand, PIK3CA gene amplification was found in 21.6% of cases and was strongly associated with distant metastasis (P = 0.002), lymph node involvement (P = 0.032), and advanced tumor stage (P < 0.001). Moreover, patients with PIK3CA copy number gain have a significant reduced overall survival time (P log rank = 0.02). We concluded that PIK3CA gene amplification is frequent in NPC and occurs in the advanced stage of NPC. Moreover, our finding emphasizes the association of PIK3CA gene amplification with worse prognosis in nasopharyngeal carcinoma.