Le carcinome nasopharyngé en Afrique du Nord et dans le Sud-Est asiatique : entre similitude et différence

Nasopharyngeal carcinoma (NPC) is an unusual head and neck cancer because of its unequal geographical distribution and its consistent association with the Epstein-Barr virus (EBV). This malignant tumor poses a serious public health problem in many countries, especially in Southeast Asia and North Africa where the recorded incidence are highest. During the past decade, a growing number of studies were undertaken to define the molecular basis of NPC. However, the analysis of several clinical and biological parameters of North African and Southeast Asian NPCs has shown notable differences, suggesting that they could result from a distinct combination of etiological factors. One intriguing characteristic of North African NPC, concerns its bimodal age distribution with a secondary peak of incidence in the range of 15-25 years, not observed in Asian NPC. In this juvenile form of NPC, immuno-histochemistry assay has shown that the two key proteins controlling the apoptotic-survival balance p53 and Bcl-2 are less frequently expressed whereas the transmembrane tyrosine-kinase receptor c-kit and the main EBV oncoprotein LMP1 were more abundant. In addition, the EBV serological alterations are less informative for the diagnosis of the juvenile compared to the adult form. In addition, most North African NPCs contain EBV strains with genetic polymorphisms distinct from those described in the Southeast Asia series (predominance of F, D, H1-H2, XhoI+ and f, C, H, XhoI– respectively). In contrast, studies relating on tumor chromosomal alterations or aberrant promoter methylation result in data very similar to those obtained from the Southeast Asia series, supporting the concept of a common molecular basis for all NPC regardless of patient geographic origin.     

Résistance au docétaxel: mécanismes et applications thérapeutiques

Docetaxel is the standard treatment for metastatic castration-resistant prostate cancer (mCRPC) patients, but its effectiveness is limited in time and tumor escape the inevitable. The various combinations with docetaxel were negative in terms of prolongation of overall survival. A better understanding of mechanisms of docetaxel resistance on microtubule and p-glycoprotein, for instance, would guide the therapeutic strategy. After the administration of docetaxel, cabazitaxel, abiraterone, alpharadin and recently MDV3100 have shown their effectiveness in improving overall survival compared to a placebo or mitoxantrone in phase III trials. Also in predocetaxel stage, sipuleucel-T has proven effective in asymptomatic mCRPC patients. The identification of predictors of response to taxanes will personalize chemotherapy to induce durable response and significantly prolonged survival.     

Les formes héréditaires du cancer de l’ovaire : particularités clinico-biologiques et thérapeutiques

Hereditary ovarian cancers account for 10% of all cases. Two major syndromes with dominant autosomal transmission are identified. The most common one is breast-ovarian cancer syndrome due to BRCA1 and BRCA2 genes mutations, and the Lynch syndrome with mutated MMR genes is the other. Alterations in homologous recombination specifically observed in ovarian cancer with BRCA defects associated to Parp inhibition create a synthetic lethality of special interest. Numerous studies are in progress to explore this promising new approach. Furthermore, it seems that carcinogenesis of these two syndromes are different, suggesting alternative therapeutic options in the near future in order to improve prognosis of ovarian carcinomas.     

Cancer et grossesse: aspects épidémiologiques et thérapeutiques

Having to start chemotherapy during pregnancy is a rare event. The decision to proceed with this treatment depends on the drugs used, how long the foetus will be exposed to them and the gestational age at the time of exposure. It is important to know the mutagenicity potential of the chosen medicine, and consequently, the risk for the child, without putting the mother’s life or health at risk. This issue mainly involves breast cancer, leukemia and lymphoma. The first trimester of pregnancy is the most critical period for the foetus, as this is when organogenesis occurs. Antimetabolites are the drugs most linked with the risk of malformation. In addition, chemotherapy may have a directly toxic effect on the foetus in utero. Myelosuppression is the most common of these, causing infections and/or foetal haemorrhage. The long term risks of cancer on fertility or the child’s intellectual development are still not well known and must be included in prospective studies, as well as being recorded in a specific data file.     

Le cancer du cavum de l’enfant et l’adulte jeune : aspects anatomocliniques,thérapeutiques et particularités évolutives

PurposeWe retrospectively analyzed anatomoclinic, therapeutic and evolutive particularities of 74 young patients (≤ 20 years) with nasopharyngeal carcinoma treated between 1993 and 2005.Patients and methodsInitial work-up included a fiberoptic nasofibroscopy with biopsy, tomodensitometry and/or MRI of nasopharynx and neck, chest X-ray, abdominal ultrasonography and bone scan. Patients were treated with either primary chemotherapy (epirubicin and cisplatin) followed by radiotherapy or concomitant radiochemotherapy (five fluorouracil and cisplatin). Radiotherapy was delivered to a total dose of 70 to 75 Gy to nasopharynx and involved cervical lymph nodes and 50 Gy to the remainder cervical areas.ResultsThe median age was 16 years. Sixty-three percent of patients had undifferentiated tumors. Sixty-six percent had locally advanced tumor. With a median follow-up of 107 months, one patient presented a local relapse, 24 patients developed distant metastases with a median delay of 7 months. The 5 years overall survival and disease-free survival were 66 and 65 %. Late complications were dominated by dry mouth and endocrine disorders.CommentsPediatric nasopharyngeal carcinoma is characterized by an early metastatic diffusion. Local control is excellent but with severe late toxicities. New techniques of radiotherapy and new molecules of chemotherapy could improve these results.     

Le cancer de la tête du pancréas vu aux urgences: aspects cliniques et thérapeutiques

Objectives

In this work, the authors present their experiment of cancer of the head of the pancreas seen to the emergency concerning 85 cases admitted to the service of the surgical emergency during a 6-year period (2000–2006).

Materials and methods

This is a retrospective study spread out over one period, from January 1^st 2000 to June 30^th 2006 at the service of the visceral surgical urgencies dealt with 85 patients carrying the cancer of the head of the pancreas diagnosed on the data from the imagery or peroperative observations.

Result

The mean age of our patients at the time of the diagnosis is of 60 years. It concerns 54 men and 31 women. The jaundice was the first sign leading the patient to consult. The majority of our patients were admitted to in a table of angiocholite (57.7%), with an often-faded general state. Abdominal echography brought the diagnosis of cancer of the head of the pancreas among 45 patients (52.9%). The abdominal tomodensitometry was produced among all our patients, and it showed a tumour of the head of the pancreas in the majority of the cases (98%), of which 55% had a tumour, which size was between 3 and 6 cm. On the therapeutic level, there were seven cases of surgical abstentions (8.2%), eight exploring laparotomies (9.4%), 48 (55.3%) biliary derivations and 17 (20%) cephalic duodenopancreatectomy; the immediate postoperative continuations were marked by the appearance of complications among six patients. In addition, postoperative death rate was of 9.7% (seven cases).

Conclusion

The cancer of the head of the pancreas is an affection of bad prognosis, because its diagnosis is often late where any gesture of excision surgical is impossible. The surgery remains the only potentially curative treatment.     

Télomères et télomérase comme cibles thérapeutiques dans le traitement du cancer

Advances in chromosome dynamics have increased our understanding of the significant role of telomeres and telomerase in cancer. Telomerase is expressed in almost all cancer cells but is inactive in most normal somatic cells. Therefore, telomerase is an important target for the design of therapeutic agents that might have minimal side effects. Herein, we evaluate current approaches to telomerase/telomere-targeted therapy, discuss the benefits and disadvantages, and speculate on the future direction of telomerase inhibitors as cancer therapeutics.     

RCMI et voies aérodigestives supérieures : le fractionnement différentiel a-t-il un intérêt ?

For head and neck cancer, intensity-modulated radiation therapy (IMRT) provides benefits in terms of coverage of the target tumour volume and reduction of the dose to organs at risk. Altered fractionation called SMART (simultaneous modulated accelerated radiation therapy) or SIB (simultaneous integrated boost), equivalent to the “concomitant boost” of conventional techniques, provides additional theoretical gain in the therapeutic index and simplifies the practical implementation of the treatment. The impact on tumour control and acute and late toxicities is encouraging but needs to be confirmed by prospective clinical studies with sufficient follow-up. A lot of different protocols have been tested without really bringing out a “gold standard”. However, the current results tend to suggest a SIB/SMART-IMRT moderately accelerated without combined chemotherapy for limited stages (I and II), and SIB-IMRT slightly accelerated with induction and/or concomitant chemotherapy for more advanced stages (III and IV).     

Sarcome d’Ewing primitif du condyle mandibulaire : difficultés diagnostiques et thérapeutiques

Introduction

Ewing’s sarcoma reached preferentially long bones; the primary involvement of the mandibular condyle is rare, causing diagnostic and therapeutic challenges. We report a case of Ewing’s sarcoma of the mandibular condyle.

Observation

A 37 year-old woman consulting for pain in the right temporomandibular articulation preceded by the extraction of tooth #18. The evolution was marked by the appearance of swelling of the parotid region. A CT-scan was done and objectified lytic aspect of the right condyle of the mandible. Resection was performed and histological examination of the surgical specimen showed a round cell tumor proliferation; CD99 immunostaining was positive and the assessment of extension was normal. Management was complemented by an expanded chemo-radiotherapy resection.

Discussion

Ewing’s sarcoma is a round cell tumor with high-grade malignity, causing diagnostic and therapeutic difficulties. Clinical appearance is polymorphic, and pathological examination is not specific, evoking several differential diagnoses. Diagnostic confirmation involves techniques of molecular biology.     

Retard diagnostique et thérapeutique du cancer du testicule au Sénégal

Introduction

Testicular cancer is a rare disease in black subjects, by disregarding the diagnosis in some cases. We report three cases diagnosed at a metastatic stage.

Patients and methods

We conducted a retrospective study of three cases of testicular cancer. We collected patient age at diagnosis, circumstances of diagnosis, the rate of tumor markers, pathologic results after resection of the tumor and complementary therapies, and morbidity and mortality. Patients have been described based on the summary of their observations.

Results

The average age of our patients was 28 years. All our patients presented at least once without a testicular cancer diagnosis has been discussed. At the histological level, it was in the three cases of non seminomatous germ cell tumors. There were lymph node metastases in our three patients and visceral involvement in two patients. Two patients out of three died during chemotherapy. The third patient had six cycles of chemotherapy with the protocol bleiomycine, etoposide, cisplatin has. Four months after the end of six treatments, he is in complete remission, thoracic and abdomino-pelvic CT scan and tumor markers were normal.

Conclusion

The rarity of testicular cancer in black subjects should not be a reason to disregard them. Late diagnosis often leads to advanced stages with poor prognosis and the need the to use more frequently adjuvant chemotherapy whose cost is not always within reach of patients in our country.     

Mécanismes de résistance aux thérapeutiques moléculaires ciblées dans le cancer du sein : constats et perspectives

The importance of targeted therapies has been emphasized by clinical trials using antiangiogenic or HER2 inhibitors in breast cancer. First with trastuzumab, it was demonstrated that targeted therapies may improve outcome in patients with HER overexpressing breast cancer in metastatic or adjuvant settings. The emerging role for angiogenesis inhibitors has also been demonstrated with bevacizumab. Unfortunately, there is growing clinical and biological evidence that tumour cells may develop unexpected and complex mechanisms of resistance to those targeted therapies. This review outlines the mechanisms by which tumour cells may resist to new targeted agents. Most recent developments are also highlighted.     

Cancers de la cavité buccale chez les sujets jeunes : résultats thérapeutiques et analyse de facteurs pronostiques

PurposeSquamous cell carcinomas of the oral cavity occurring in young people represent a specific entity. Its management and prognosis are controversial. We performed a retrospective chart review of all patients aged less than 40 years old and treated at Gustave-Roussy Cancer Centre for a squamous cell carcinomas of the oral cavity between 1999 and 2011.MethodsPatients and tumour characteristics, type of treatment and follow-up data were collected. Survival data were analysed according to the methods of Kaplan-Meier and both univariate and multivariate analyses were performed to look for prognostic factors regarding overall survival and progression-free survival.ResultsSixty-three patients were identified. Median follow-up was 64 months. Most of the tumours were initially located in the mobile tongue (n = 54, 85.7%). Overall 17 patients had died, including 15 from the treated cancer. Overall and progression-free survival rates at 5 years were respectively 79.6% and 68.6%. The corresponding 5 years local, regional and metastatic relapse free survival rates were 80%, 91% and 89% respectively. In the multivariate analysis only the absence of initial surgery (hazard ratio [HR]: 13.5 [2.0; 90.5]; P = 0.007) was prognostic for overall survival, while alcohol abuse (HR: 0.37 [0.15; 0.9]; P = 0.03) and the absence of surgery (HR: 13.6 [2.5; 74.2]; P = 0.002) were associated with a decreased progression-free survival. A younger age (less than 30 year old) was not associated with the risk of recurrence or death.ConclusionSurvival rates and tumour control probabilities are relatively high among young patients suffering from squamous cell carcinomas of the oral cavity treated at a tertiary centre. The early identification of patients at risk of relapse is currently difficult. The balance between recurrence and treatment toxicity warrants further studies, both on the clinical level and for the development of prognostic biomarkers.     

Irradiation partielle accélérée du cancer du sein : aspect théorique

Hypofractionated and accelerated partial breast irradiation are more and more widely used for early breast cancer. Here, this short communication would expose the role of hypofractionated radiotherapy in adjuvant breast radiotherapy, rational, techniques and indications of accelerated partial breast irradiation.     

Les cancers colorectaux métastatiques dans le sud tunisien: étude clinique et résultats thérapeutiques

Purpose

The objective of this retrospective study was to discuss the epidemioclinical criteria and the therapeutic results relative to metastatic colorectal cancer.

Patients and methods

The study concerned 130 patients who presented with metastatic colorectal cancer at diagnosis or who had developed late metastasis. We reviewed the epidemioclinical records of all the patients. Treatment consisted in metastasectomy followed by chemotherapy or chemotherapy followed by metastasis resection if possible. Response and toxicity were assessed according to WHO criteria.

Results

There were 86 patients who were metastatic at diagnosis and 44 who had developed late metastasis. The mean age was 55.5 years (sex-ratio: 1.04). Patients were frequently symptomatic. Liver metastases were the most common, followed by lung, node and peritoneal localisations. Fifteen patients underwent metastasis resection first and 6 were resected after cytoreductive chemotherapy. First line chemotherapy was: LV5FU2 (37%), FOLFIRI (33%) and FOLFOX4 (30%) with an objective response rate of 28% (CR: 45%) and a mean remission duration of 17 months. Fifty-nine patients received second line chemotherapy and 14 received a third line. The median survival was 19 months for all treated patients and the mean survival in patients with resected metastasis was 40 months. The overall survival rate was respectively 43, 25.8 and 9% at 2, 3 and 5 years.

Conclusion

Our study was characterized by the frequency of synchronous metastasis, young age and symptomatic disease. Therapeutic results were satisfying and would be improved if there were more resecable metastases, as the rate in our sample was particularly low.     

Radiothérapie et thérapie ciblée pour la prise en charge du cancer du sein : mise au point

The purpose of this study was to review the current knowledge regarding combinations of the most commonly used targeted therapies or those under development for the management of breast cancer with radiation therapy. Several studies have shown that the combination of radiation therapy and tamoxifen increased the risk of radiation-induced lung toxicity; therefore, the two modalities are generally not given concurrently. The combination of HER2 inhibitors (trastuzumab, pertuzumab) and radiation therapy appeared to be safe. However, trastuzumab emtansine (T-DM1) should not be given concomitantly with brain radiation therapy because this combination may increase the risk of brain radionecrosis. The combination of radiation therapy with other new targeted therapies such as new selective estrogen receptor modulators (SERDs), lapatinib, cell cycle inhibitors, immune checkpoint inhibitors, or molecules acting on DNA damage repair seems feasible but has been mainly evaluated on retrospective or prospective studies with small numbers of patients. Moreover, there is a great heterogeneity between these studies regarding the dose and fractionation used in radiotherapy, the dosage of systemic treatments and the sequence of treatments used. Therefore, the combination of these new molecules with radiotherapy should be proposed sparingly, under close monitoring, pending the ongoing prospective studies cited in this review.     

Cancer du sein triple-négatif : caractéristiques histocliniques et moléculaires,prise en charge et perspectives thérapeutiques

Triple-negative breast cancer (TNBC), as defined by the absence of estrogen and progesterone receptor expression, as well as the lack of HER2 overexpression/amplification, corresponds to 15% of breast cancer and represents an aggressive form of the disease. TNBC are frequently confounded with basal subtype in the molecular classification of breast cancer and also share some similarities with BRCA1-mutated tumors. Epidemiological and clinical characteristics are distinct from other subtypes, including a younger age at diagnosis, a higher risk of relapse in spite of increased chemosensitivity, and a higher incidence of lung and brain metastatic relapses. Conventional cytotoxics remain the mainstay of current systemic management but recent evaluation of more targeted therapeutics, including specific cytotoxics (such as the use of platinum salts), PARP and EGFR inhibition, and antiangiogenics have been performed, providing contrasted but rather disappointing results. Recent data indicate that TNBC represent a heterogeneous entity composed of multiple and distinct molecular subtypes, which should deserve specific targeted therapeutics.