Curiethérapie des cancers des voies aérodigestives supérieures

The main indications of brachytherapy for head and neck cancers are limited tumours of the oral cavity, the oropharynx and the nasopharynx. This technique can be exclusive, associated with external radiotherapy or postoperative. This is also a treatment for second localizations in previously irradiated areas. If low-dose rate brachytherapy is the reference, the pulse dose rate brachytherapy by control of the dose rate and optimisation of the dose distribution is the technique to be preferred. High-dose rate brachytherapy is an option. The major prognosis factors of local control and complications are the use of a leaded protection of the mandible, the intersource spacing (1.2–1.4 cm), the volume treated (30 cm³, i.e. three loops), the safety margin (5 mm), the dose rate (0.5 Gy/h), the total dose (65 Gy in case of exclusive brachytherapy, 25 Gy in case of a combination of external beam irradiation [50 Gy] and brachytherapy in the oropharyngeal carcinomas, 35 Gy in case of a combination of external beam irradiation [40 Gy] and brachytherapy in the oral cavity carcinomas, 60 Gy in case of a second localization in previous irradiated tissues), the delay between external irradiation and brachytherapy (< 20 days), the dose per fraction and the treated volume for high-dose rate brachytherapy. Brachytherapy, when possible, is the optimal method of irradiation of head and neck carcinomas with limited volume.     

Réirradiation des cancers des voies aérodigestives supérieures

Locoregional relapse in previously irradiated region for head and neck tumours is associated with a bad locoregional and distant prognosis. Reirradiation might be exclusive, or feasible in addition with surgery and/or chemotherapy, according to histopronostic factors. Data show that reirradiation is feasible with some severe toxicity due to the bad prognosis of this situation. Hyperfractionnated regimen with split course or normofractionnated regimen without split course are possible with similar efficacy. If tumour size is small, stereotactic ablative radiotherapy may be considered, and if the treatment centre has proton therapy, it could be proposed because of better organs at risk sparing. There is no standard regarding reirradiation schedules and several trials have to be done in order to determine the best technique. Nevertheless, it is agreed that a total dose of 60 Gy (2 Gy per fraction) is needed. Other trials testing the association with new systemic agents have to be performed, among them agents targeting the PD1/PD-L1 axis.     

Conséquences des traitements des cancers et préservation de la fertilité

Cancer prognosis has considerably improved over recent decades and increasing numbers of young adults live with the long-term consequences of their treatment. Their quality of life is often serious compromised by the inability to conceive a child. As such the recent and rapidly evolving practice of fertility preservation needs to become a standard option in cancer care. Embryos, oocytes, spermatozoa, and germinal tissue can be cryopreserved without damage until such time that the patient, freed from their illness can envisage starting a family. Fertility can be persevered prior to initiation of gonadotoxic treatments by different methods. Some options, in particular in prepubescent boys (and even in adolescents and young adults), though a high research priority and a source of great hope, remain highly experimental. Since the available options combine both validated and experimental methods, it is necessary that care teams are multidisciplinary and that they discuss these choices with the patient and (for children) their family. Even though some patients, through choice or otherwise, are not candidates for Fertility Preservation, their decision, taken in the light of complete, correct and understandable information about the available options, must be respected in accordance with their rights to determine their own reproductive future. The current situation in France needs improvement and multidisciplinary structures are forming where cancer specialists work closely with specialists in reproductive medicine and biology to provide rapid and coordinated patient care. The national cancer institute (INCA) with the Agence de la biomédecine have co-published a report that brings the knowledge of all involved in the care of these patients up to date and makes a series of propositions to improve the situation and notably to guarantee equitable access to quality care for all concerned persons. The principal areas of improvement are:

• — Equitably improve cancer patients’ access to fertility preservation across the country through the regional planning and establishment of multidisciplinary teams, supported by targeted funding and the authorisation of centres.
• — Publish and disseminate professional guidelines and verify that they are taken into account during multidisciplinary decision making.
• — Systematically inform patients and their families about the consequences of cancer therapy on reproductive function.
• — Set up longitudinal cohorts of patients.
• — Promote research into how to prevent or reduce the risk of the attenuation of fertility and into how to restore it.

     

Les récidives des tumeurs des voies aérodigestives supérieures

Recurrences of tumours of the upper aerodigestive tract are frequent despite the improvement of the primary treatment and they limit the rate of survival long-term. They occur in patients with multiple co-morbidities, often associated with sequelae or side effects of earlier treatments. The salvage treatment will add a cumulative toxicity and therapeutic options are limited. The choice will go from curator to palliative treatment. The report benefit-risk must be assessed in each case depending on the terrain and prognostic factors that have been identified, such as performance status, the time between initial disease and the recurrence, the site and the stratification of the recurrence. In operable non-metastatic recurrence surgery remains the treatment of choice. Multimodal treatment involving surgery, radiation therapy and chemotherapy in this context is being evaluated. Non-operable tumors have long been considered only in a palliative context. The evaluation of detailed irradiation as bifractionnated radiotherapy combined with chemotherapy helped establish protocols allowing long-term survivals and consider these treatments as potentially curators. However, the toxicity of these treatments is important. That is why the technical innovations of the radiation and the development of new chemotherapeutic agents today offer opportunities remaining to assess. The use of irradiation targeted by intensity-modulated radiation therapy (IMRT), and stereotactic radiotherapy by decreasing the irradiated volume should decrease the toxicity. Generally better tolerated than conventional chemotherapy agents, targeted therapies also took their places associated with radiotherapy in the treatment of these patients already treated. Cetuximab was the first agent obtaining an indication. Other agents are being evaluated in metastatic recurrent tumors, including exploring the possibilities of radiopotentialisation nanoparticles and the inhibitors of apoptosis proteins.     

Boost et réirradiation stéréotaxiques des cancers des voies aérodigestives supérieures

Stereotactic radiotherapy is increasingly used in head and neck tumours, either as a boost for dose escalation/early salvage, or in the reirradiation setting. We aimed to assess the level of evidence for each clinical setting and to discuss the different dose and frationation regimens. A search of the French and English literature was performed on PubMed until December 2013. Stereotactic reirradiation of locally recurrent squamous cell carcinomas can be performed with overall survival rates of about 12 months with good quality of life, and acceptable toxicity, based on several phase 2 trials and retrospective studies. Nasopharyngeal carcinomas may be irradiated with even better control rates. Late severe toxicities yield up to 20–30%. Patient and tumour selection criteria (limited volume) and dose constraints to the carotids (cumulative dose 110 Gy or less, to avoid the risk of potentially lethal carotid blowout) must be carefully chosen. Fractionated regimens (at least five fractions) should be preferred (30 Gy in five fractions to 36 Gy in six fractions). Methods derived from stereotactic, intensity-modulated radiotherapy (IMRT) may be used with conventional fractionation for larger tumours. Stereotactic irradiation may be associated with cetuximab; data with chemotherapy or other targeted therapies are still lacking. Stereotactic irradiation is also used as a boost after 46 Gy IMRT in several institutions or for early salvage (8 to 10 weeks following full dose irradiation with evidence of residual tumour) in squamous or nasopharyngeal carcinomas. Such indications should be evaluated prospectively in clinical trials. Data in salivary gland and sinonasal neoplasms are still scarce. In conclusion, stereotactic body radiation therapy has the potential as a boost or in the reirradiation setting to improve local control in head and neck tumours. Careful hypofractionation with planning caring for the dose to the main vessels is highly recommended. Prospective studies with prolonged follow-up (at least 2 years) should be encouraged.     

Place des thérapeutiques moléculaires ciblées dans les carcinomes épidermoïdes des voies aérodigestives supérieures

The development of molecular targeted therapies in oncology is currently experiencing rapid growth, focusing primarily on two large categories of molecules, monoclonal antibodies and tyrosine-kinase inhibitors. Their action is directed at different molecular targets, particularly receptors of the HER family such as the epidermal growth factor receptor (EGFR or HER1) and biological factors involved in the neoangiogenesis process such as VEGF. Cetuximab, an anti-EGFR monoclonal antibody, has been shown to be effective in the treatment of epidermoid carcinoma of the upper aerodigestive tract in association with radiotherapy (locally advanced tumors) or with conventional cytotoxic agents (recurrent or metastatic tumors). Intensive research efforts are currently ongoing to develop new molecules with original specific biological targets or able to interact with several molecular pathways, to combine these therapies either amongst themselves or with conventional therapeutic agents (radiotherapy and chemotherapy) and, above all, to determine the predictive factors of their efficacy and toxicity.     

Curiethérapie des sarcomes des tissus mous des membres

The standard of care of local treatment for extremities soft tissue sarcomas relies on conservative surgery combined with external beam radiotherapy. Brachytherapy can be realized instead of external beam radiotherapy in selected cases, or more often used as a boost dose on a limited volume on the area at major risk of relapse, especially if a microscopic positive resection is expected. In these cases, this combination allows to obtain the best local control rates published. Close interaction and communication between radiation oncologist and surgeon are mandatory at the time of implantation to limit the risk of side effects. Long-term results are available for low-dose rate brachytherapy. Nowadays, pulsed dose rate is more often used. More limited experience has been reported for high dose rate.     

Prise en charge des mucites après radiothérapie des cancers des voies aérodigestives supérieures

Acute mucositis is common after radiotherapy for head and neck cancers. Duringthepast3 decades, there was a gradual evolution in the treatment modalities for locally advanced carcinomas (concomitant radio-chemotherapy, accelerated radiotherapy). These new strategies are accompanied by an increase in early mucosal reactions. Atthe present time, there is no widely accepted prophylaxis or effective treatment. Many traditional remedies or new agents seem ineffective (Sucralfate, Chlorhexidine, GM-CSF, Silver nitrate, Prostaglandin, anti-oxiclants, Benzydamine hydrochloride), while others seem promising (Poviclone-iodine, nonabsorbable antibiotic lozenges and antifungals, local GM-CSF, Gluta-mide, Low-energy laser, corticosteroïds). Radioprotectors are controversial and should be only used in experimental protocols and not in routine practice. However, some recommendations can be proposed: general prevention and global care before cancer therapy should be systematic (oral hygiene, dental and periodontal treatment, advice to avoid the use of tobacco and alcohol); frequent oral rinsing with a bland mouthwash (Povidone-iodine or others) should be used at the start of treatment because there are significant modifications of the oral microflora increased by a disturbed salivary flow; these mouthwashes could be associated with nonabsorbable antibiotic lozenges or antifungal topicals (bicarbonates, Amphotericine B); Systematic percutaneous fluoroscopic gastrostomy should be decided before any aggressive treatments (concomitant radio-chemotherapy, accelerated radiotherapy); pain should be controlled; finally, the radiation technique should be optimized (mucosal-sparing block, conformai radiotherapy and intensity-modulated radiation therapy).     

Réirradiations des carcinomes épidermoïdes des voies aérodigestives supérieures : indications et résultats

Despite progress in the management of head and neck squamous cell carcinoma (HNSCC), a significant proportion of patients previously irradiated for head-and-neck cancer will develop locoregional recurrence or a second primary. Because of the heterogeneity of this population with respect to disease-related factors (localization, volume, recurrence or second primary, time interval from previous irradiation…) and patient-related factors (comorbidities, sequelae of previous irradiation…), the optimal reirradiation treatment remains to be defined. Salvage therapy using reirradiation, despite some encouraging results, has historically been avoided because of concerns regarding toxicity. The results of more recent studies using contemporary treatment techniques and conformal delivery methods such as intensity modulated radiation therapy (IMRT) or stereotactic radiotherapy (SBRT) have been somewhat more promising. The aim of this review is to discuss the reirradiation of HNSCC in terms of patient selection and modern radiotherapy techniques.     

Traitements médicamenteux des métastases cérébrales des cancers du sein HER2+

Breast cancer is the second leading cause of brain metastases. In patients with HER2-positive breast cancer, the incidence of brainmetastases is 40%. Although the arrival of anti-HER2 therapies has meant better control of other metastatic diseases, progress still needs to be made with regard to therapies for treating brain metastases. Currently, research is concentrating on chemoradiotherapy combinations, anti-HER2 and chemotherapy combinations, more specifically, combining lapatinib and capecitabine, or even intrathecal administration of herceptin.     

Chimiothérapie systémique des cancers avancés des voies biliaires: actualités et perspectives

Biliary tract cancers, with fewer than 2,000 new cases per year in France, must be regarded as orphan tumors. There is currently no evidence of the benefit of neoadjuvant or adjuvant chemotherapy and/or radiotherapy in resectable biliary tract cancers. In unresectable disease, best supportive care is the mainstay of treatment, especially effective biliary drainage. Gemcitabinecisplatin combination (GEMCIS regimen) is the first standard for first-line palliative chemotherapy in patients with advanced biliary tract cancer and correct performance status. Despite the absence of randomized controlled trials comparing GEMCIS and gemcitabine-oxaliplatin (GEMOX) regimens, the latter represents an interesting option. Currently, no data allow to define a standard for second-line and further therapies. Future therapeutic advances will likely come from the combination of targeted agents with chemotherapy, with selection of patients on tumor oncogenic alterations of interest.     

Délinéation des volumes cibles anatomocliniques pour la radiothérapie des cancers du col utérin

Concurrent chemoradiation followed by brachytherapy is currently the standard treatment for locally advanced cervix carcinomas. Modern radiation techniques require planning based on 3D images, and therefore an accurate delineation of target volumes. The clinical target volume (CTV) used for the different phases of treatment are now well defined, but are not always easy to delineate on a CT scan which is currently the standard examination for simulation in radiotherapy. MRI and PET-CT are routinely performed at diagnosis, and can be used to improve the accuracy of the delineation. The objective of this review is to describe the definitions and recommendations of CTV in the treatment of cervical cancer.     

La curiethérapie interstitielle périoperatoire dans le traitement des cicatrices chéloïdes récidivantes

PurposeEvaluation of the results of perioperative interstitial brachytherapy with low dose-rate (LDR) Ir-192 in the treatment of keloid scars.Patients and methodsWe performed a retrospective analysis of 73 histologically confirmed keloids (from 58 patients) resistant to medicosurgical treated by surgical excision plus early perioperative brachytherapy. All lesions were initially symptomatic. Local control was evaluated by clinical evaluation. Functional and cosmetic results were assessed in terms of patient responses to a self-administered questionnaire.ResultsMedian age was 28 years (range 13–71 years). Scars were located as follows: 37% on the face, 32% on the trunk or abdomen, 16% on the neck, and 15% on the arms or legs. The mean delay before loading was four hours (range, 1–6 h). The median dose was 20 Gy (range, 15–40 Gy). Sixty-four scars (from 53 patients) were evaluated. Local control was 86% (follow-up, 44.5 months; range, 14–150 months). All relapses occurred early – within 2 years posttreatment. At 20 months, survival without recurrence was significantly lower when treated lengths were more than 6 cm long. The rate was 100% for treated scars below 4.5 cm in length, 95% (95% CI: 55–96) for those 4.5–6 cm long, and 75% (95% CI: 56–88) beyond 6 cm (p = 0.038). Of the 35 scars (28 patients) whose results were reassessed, six remained symptomatic and the esthetic results were considered to be good in 51% (18/35) and average in 37% (13/35) (median follow-up, 70 months; range, 16–181 months).ConclusionEarly perioperative LDR brachytherapy delivering 20 Gy at 5 mm reduced the rate of recurrent keloids resistant to other treatments and gave good functional results.     

Traitements systémiques des métastases cérébrales des cancers du sein : chimiothérapies cytotoxiques et thérapies ciblées

Prevalence of brain metastases is increasing in breast cancer. Brain metastases represent a poor-prognosis disease for which local treatments continue to play a major role. In spite of the presence of a physiological blood-brain barrier limiting their activity, some systemic treatments may display a significant antitumor activity at the central nervous system level. In HER2-positive metastatic breast cancer with brain metastases not previously treated with whole brain radiotherapy, capecitabine and lapatinib combination obtains a volumetric reponse in two thirds of patients (LANDSCAPE study). If confirmed, these results could modify in selected patients the layout of therapeutic strategies. Promoting novel targeted approaches and innovative therapeutic combinations is a critical need to improve survival of breast cancer patients with brain metastases.