Cancers des voies aérodigestives supérieures : le retour de la chimiothérapie néoadjuvante ?

Chemotherapy is a part of the combined multimodality treatment for locally advanced head and neck cancers. Concomitant administration with radiation therapy is the standard treatment for these patients. The efficacy of the docetaxel–cisplatinum–5-fluoro-uracil (TPF) regimen compared to the platinum–5-fluoro-uracil (PF) regimen raised the question of whether this treatment could improve the therapeutic results for locally advanced tumours. For larynx preservation, induction chemotherapy using TPF, followed by radiation therapy for good responders is a valid option. However, clinical studies have to be performed to compare this approach to the concomitant radiation therapy–chemotherapy approach using functional endpoints. For locally advanced tumors, despite the superiority of the TPF regimen over the PF, there is no evidence in the literature to support the use of induction chemotherapy prior to concomitant radiation therapy–chemotherapy. Two recent studies (DECIDE, PARADIGM) failed to demonstrate any benefit, but both trials were stopped early because of slow enrollment. Other studies are on going, or with recently finished accrual, will help to shed light on the role of this treatment     

Place et intérêt de la chimiothérapie d’induction des cancers des voies aérodigestives supérieures

Induction chemotherapy must be integrated in a global approach for locally advanced head and neck cancer. Its use has theoretical advantages but should not compromise locoregional radiotherapy. Induction chemotherapy is a standard for organ preservation with the use of the TPF scheme to avoid total laryngectomy without compromising survival data. It is more controversial in other locally advanced head and neck cancer because concurrent chemoradiotherapy is the standard of care. It may be an option for patients with significant lymph node invasion to reduce the occurrence of distant metastasis.     

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.     

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.     

État buccodentaire des patients avant radiothérapie des voies aérodigestives supérieures : analyse prospective de 48 patients

PurposeThe treatment by irradiation of tumours of the upper head and neck tract cause many complications on the oral sphere, such as mucositis, dysphagia, asialia and tooth decay. Associated manifestations are frequent and their severity has been poorly studied. However, the patient's quality of life is directly correlated with their oral health.Patients and methodsWe carried out an evaluation of the oral health of 48 patients with an upper head and neck tract cancer treated by irradiation at the Paul-Strauss Centre in Strasbourg. The inclusion criteria of this study concerned the localization of the tumour in the upper head and neck tract and a treatment by irradiation associated or not to chemotherapy.ResultsThe patients of the study were concerned by alcohol and smoking intoxication, on average, 22.2 pack-year and 2.2 glasses of alcohol per day. They received an irradiation of 60.9 Gy on average. Their oral health was characterized by a DMFT (decayed, missing, filled teeth) index of 16.1, with, in mean, eight missing teeth and eight filling teeth and, by the presence of dental plaque in 70% of cases. Along the treatment by irradiation, the oral complications evaluation showed that on average, patients developed mucositis 18 days after the beginning of radiotherapy, xerostomia after 20 days, and dysphagia after 17 days. At the end of the treatment, we noted an oral hygiene improvement, with teeth brushing more frequent (two to three per day), mouthwash use, and daily fluoride prophylaxis.ConclusionThis study provides insights of the dental status of patients irradiated in the oral cavity. This series lays the groundwork for the study of prosthesis requirement and dosimetry calculation.     

Radiothérapie conformationnelle avec modulation d’intensité des cancers des voies aérodigestives supérieures : enjeux éthiques et méthodologiques

Numerous studies have shown that intensity-modulated radiation therapy is the standard technique for the radiation treatment of head and neck cancers. Intensity-modulated radiation therapy reduces side effects (xerostomia, dysphagia, fibrosis, etc.) and improves the results for cancer localizations with highly complex shapes such as the cavum or nasal cavity. Intensity-modulated radiation therapy is also a costly technique that necessitates a numerous staff, highly trained, with regular practice. If this technique cannot be available (understaffing, overwork, etc.) the choice between entrusting the patient to a colleague and treating the patient with a less sophisticated technique such as 3-dimensional conformal radiation therapy depends on different objective and ethical criteria.     

Intérêts et conflits d’intérêts: le point de vue d’un expert

An increasing part of funding in research comes from industries. Many studies show that the source of funding has a strong impact on the results and the presentation of the studies, in all the fields of biomedical research. There are multiple, nonexclusive, mechanisms, including the questions addressed by the studies, the study quality, and publication biases. This first phenomenon is amplified by the impact of the funding source on the citation rate, through various citation biases. However, the studies do not rule out the veracity of the published facts, but highlight the issues of the pertinence of the addressed questions, the communication, and the perception of the results. Since around 10 years, most of the expertise agencies implemented stringent rules for the management of competing interests and many proposals have been made for research. A part of the solution comes from a better knowledge of this phenomenon and its management at all the levels of the development and use of scientific research.     

Radiothérapie encéphalique en totalité des métastases cérébrales : intérêts et controverses dans le cadre d’un référentiel

Whole brain radiation therapy is the angular stone of the brain metastasis radiation therapy. This treatment allows reaching two goals, potentially curative for in place metastasis and prophylactic in the rest of brain tissue. However, these two advantages can be disputed and in light of the same data opposite conclusions could be drawn.     

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.     

État dentaire des patients atteints d’un cancer des voies aérodigestives supérieures

In France, in 2005, there were approximately 16,000 new cases of head and neck cancer. These cancers have an unfavourable prognosis: the survival rates at 3 and 10 years are 50% and 10% respectively. The consumption of alcohol and tobacco is the most important risk factor; in some countries HPV infection was identified as a risk factor of head and neck tumours. Furthermore, a poor oral hygiene seems to raise this risk. We found many decay and periodontium problems in patients with an upper aerodigestive tract cancer. An evaluation of dental state is necessary before any cancer treatment. Treatments by radiotherapy engender noxious effects: hypocellular, hypovascularization, hypoxie of the irradiated tissues, which lead to immediate and chronically oral complications such as mucositis, fibrosis, xerostomia, decay, or osteoradionecrosis. An oral follow-up of these patients can prevent these complications, or reduce the severity of oral complications, and promote a good oral state.     

Évaluation d’un score prédictif de dénutrition chez les patients pris en charge par irradiation pour un cancer des voies aérodigestives supérieures : étude rétrospective chez 127 patients

PurposeThe purpose of this study was to establish a pre-therapeutic score that could predict which patients would be at high risk of enteral tube feeding during (chemo)-radiotherapy for head and neck cancer.Patients and methodsA monocentric study was conducted retrospectively on patients receiving a radiotherapy or concurrent chemoradiotherapy for a head and neck cancer. A logistic model was performed in order to assess clinical or therapeutic risk factors for required artificial nutrition during treatment. Significant parameters, issued from multivariate analysis, were summed and weighted in a score aiming at estimating a malnutrition risk during radiotherapy.ResultsAmong the 127 evaluated patients, 59 patients required artificial nutrition during radiotherapy. In multivariate analysis, predictive factors for malnutrition were weight loss superior to 5% in the 3 months before radiotherapy, advanced tumor stage (III–IV vs. I–II), and pain requiring strong analgesics (step II–III vs. I). Concurrent chemotherapy was identified as a significant risk factor also, but it was strongly correlated with the tumor stage. The score, estimated from these previous factors, allowed a prediction of a risk of enteral feeding with a sensitivity of 90% and a specificity of 85%.ConclusionA predictive score of enteral nutrition before radiotherapy of head and neck cancer should be a useful clinical tool to target the patients who would need a prophylactic gastrostomy. Our study evidenced some risk factors of malnutrition requiring artificial feeding. However, we need a prospective study to confirm the validity of this score.     

Apport de l’imagerie fonctionnelle dans la radiothérapie des cancers des voies aérodigestives supérieures : vers l’adaptation à la biologie ?

Radiotherapy based on functional imaging consists to deliver a heterogeneity dose based on biological proprieties. This approach is termed biologically conformal radiotherapy or dose painting with biological target volume inside the gross tumor volume. Diffusion-weighted magnetic resonance imaging (MRI) and dynamic contrast-enhanced MRI can also be used to define a specific biological target volume. Three main tracers are used: (¹⁸F)-fluorodeoxyglucose to target the hypermetabolism, (¹⁸F)-fluoromizonidazole and (¹⁸F)- fluoroazomycin arabinoside to target areas of hypoxia. In this review, we give a practical approach to achieving a treatment-guided radiotherapy molecular and the main issues raised by this imaging technique. Despite the provision of all the technological tools to the radiotherapist, this new therapeutic approach is still evaluated in clinical studies to demonstrate a real clinical benefit compared to radiotherapy based on anatomic imaging.     

Carcinome neuroendocrine à petites cellules des voies urinaires excrétrices supérieures : à propos d’un cas

Small cell neuroendocrine carcinoma of the upper urinary tract is extremely rare. To our knowledge, only 25 cases have been reported in the literature. The current study reports the case of an 80-year-old patient who suffered from macroscopic haematuria. A first screening by thoracic-abdominal-pelvic CT scan showed a mass located in the patient's left ureter and a left nephro-ureterectomy was consequently performed. The pathological examination of the resected specimen allowed the diagnosis of a small cell neuroendocrine carcinoma of the left ureter. After four months of follow-up, a PET-CT detected an isolated local recurrence on the left common iliac lymphadenopathy. After seven cycles of chemotherapy (carboplatin-etoposide), we observed a partial response followed by a new progression. It was then decided to perform an image-guided radiotherapy at a dose of 46.8 Gy, at 1.8 Gy per fraction, during 37 days to the left common iliac lymphadenopathy. After 16 months of follow-up, a complete metabolic remission was achieved. Indeed, this observation, followed by a short literature review, demonstrates the interest of radiotherapy for the treatment of a rare cancer: the small cell neuroendocrine carcinoma of the upper urinary tract.     

Y a-t-il un intérêt au curage lomboaortique dans les cancers de l'endomètre opérables ?

The indication and extent of lymph node dissection in the surgical management of endometrial cancer remains controversial especially concerning the para-aortic lymph nodes. The therapeutic benefit of the lymph node dissection is criticized mainly for low-risk patients for extra-uterine spread. Surgically staging patients is the best method to predict node involvement and it allows an optimal decision for adjuvant therapy to be taken. The different prognostic factors for para-aortic lymph nodes metastasis are histological grade and size of the tumour, myometrial wall invasion and lymphovascular dissemination, as well as positive pelvic lymph nodes. However, these elements are not correctly evaluated before and during the surgery. Positive para-aortic lymph nodes can be found without a lymphatic spread to the pelvic area. Even though the prevalence of para-aortic node involvement is weak, it seems legitimate to propose in selected cases of important lymph node involvement, it's complete dissection if a pelvic lymphadenectomy is indicated and if it is surgically possible.     

Quelle place pour la radiothérapie et la chimiothérapie dans le traitement adjuvant des carcinomes urothéliaux des voies excrétrices urinaires supérieures ?

Urothelial carcinomas of the upper urinary tract are rare entities. Surgery remains the mainstay of the management. The use of others therapeutic modalities is not clearly defined yet. However, the frequency of local recurrence and locoregional encourage us to evaluate the indication of adjuvant therapies. We conducted a synthesis of key data in the literature on the use of chemotherapy and radiotherapy in the treatment of urothelial carcinoma of the renal pelvis and ureter. A literature search on PubMed was performed using the following keywords (MeSH) “urothelial carcinoma”, “upper urinary tract”, “radiation”, “chemotherapy”, and adjuvant.     

Facteurs pronostiques de la ré-irradiation des cancers des voies aérodigestives supérieures : revue de la littérature

Purpose

To specify the effectiveness of head and neck cancer reirradiation and make a synthesis of prognostic factors established by published series of patients.

Paramètres de radiorésistance des cancers des voies aérodigestives supérieures et stratégies de radiosensibilisation

Head and neck cancers have been widely studied concerning their sensitivity to radiation therapy. Several parameters affect tumour response to radiation therapy. Some parameters are linked to the tumour. Large or invasive tumours, localization, such as oral cavity or adenopathy, are factors of radioresistance. Others parameters are linked to the patients themselves. Tobacco intoxication during radiotherapy and a low hemoglobin level contribute to radioresistance. More recently, a positive human papilloma virus (HPV) status has been reported to positively affect radiosensitivity. Finally, other parameters are related to tumour biology. Hypoxia, intrinsic radiosensitivity of tumour cells, tumour differentiation and repopulation (provided by Ki-67 index or EGFR level) are components of radiosensitivity. Currently, concurrent chemoradiotherapy is one of the gold standard treatments to overcome clinical outcome of locally advanced head and neck cancer. This combination increases locoregional control and survival. Taxane-based induction chemotherapy can also be an alternative. Another validated approach is the association of radiotherapy with cetuximab (EGFR targeting) but only one randomized study has been published. Fractionation modifications, especially hyperfractionation, have given positive results on both tumour control and survival. Strategies targeting hypoxia improve locoregional control but have less clinical impact.