RESUMEN
BACKGROUND: Radiotherapy is one of the cornerstones of the treatment of Head and Neck Squamous Cell Carcinomas (HNSCC). However, radioresistance is associated with a high risk of recurrence. To propose strategies (such as combinations with drugs) that could over intrinsic radioresistance, it is crucial to predict the response to treatment. Patient-Derived Tumor Organoids (PDTO) are in vitro tridimensional microtumors obtained from patient' own cancer samples. They have been shown to serve as reliable surrogates of the tumor response in patients. METHODS: The ORGAVADS study is a multicenter observational trial conducted to investigate the feasibility of generating and testing PDTO derived from HNSCC for the evaluation of sensitivity to treatments. PDTO are obtained after dissociation of resected tumors remaining from tissues necessary for the diagnosis. Embedding of tumor cells is then performed in extracellular matrix and culture in medium supplemented with growth factors and inhibitors. Histological and immunohistochemical characterizations are performed to validate the resemblance between PDTO and their original tumor. Response of PDTO to chemotherapy, radiotherapy and innovating combinations are assessed, as well as response to immunotherapy using co-cultures of PDTO with autologous immune cells collected from patient blood samples. Transcriptomic and genetic analyses of PDTO allow validation of the models compared to patients' own tumor and identification of potential predictive biomarkers. DISCUSSION: This study is designed to develop PDTO models from HNSCC. It will allow comparing the response of PDTO to treatment and the clinical response of the patients from whom they are derived. Our aim is to study the PDTO ability to predict the clinical response to treatment for each patient in view of a personalized medicine as well as to establish a collection of HNSCC models that will be useful for future innovative strategies evaluation. TRIAL REGISTRATION: NCT04261192, registered February 7, 2020, last amendment v4 accepted on June, 2021.
Asunto(s)
Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/terapia , Neoplasias de Cabeza y Cuello/patología , Terapias en Investigación , Organoides/patologíaRESUMEN
PURPOSE: Acute radiodermatitis (ARD) is a frequent side effect of radiotherapy, a therapeutic option for head and neck squamous cell carcinoma (HNSCC). It is responsible for pain, quality of life (QoL) impairment, and increased risk of treatment discontinuation, which may compromise the prognosis for patients. Local therapies to prevent or alleviate ARD have been proposed without providing any high level of evidence to establish recommendations. METHODS: We implemented a prospective multicenter randomized study on patients with HNSCC treated with definitive radiotherapy to assess the impact on ear, nose, and throat (ENT) pain of the application of a hydrogel-based skin dressing (HydroTac®) compared with the application of hyaluronic acid (Ialuset®) during radiotherapy. RESULTS: Out of 130 enrolled patients, 48 patients per group were assessable for the main endpoint. No difference between groups was found: a worsening of ENT pain of 3 points or more on a visual analog scale from the initiation to 1 month after the end of the radiotherapy was observed for 8 patients (16.7%) who received HydroTac® compared to 13 patients (27%) who received Ialuset® (p = 0.342). The proportion of patients who experienced ARD and grades of ARD (CTCAE v4.0 criteria) were similar between groups. Patient compliance with radiodermatitis treatment was poor, with 56.1% of patients in the HydroTac® group having their treatment temporarily stopped. CONCLUSION: The application of a hydrogel dressing to prevent ARD during radiotherapy for HNSCC patients has failed to demonstrate a benefit. These results may be limited by the difficulties of applying the dressing.
Asunto(s)
Neoplasias de Cabeza y Cuello , Radiodermatitis , Humanos , Ácido Hialurónico , Calidad de Vida , Radiodermatitis/etiología , Radiodermatitis/prevención & control , Carcinoma de Células Escamosas de Cabeza y Cuello , Hidrogeles , Estudios Prospectivos , Neoplasias de Cabeza y Cuello/radioterapia , Dolor , VendajesRESUMEN
PURPOSE: To compare two types of CT acquisition parameters: CT scan of the facial bone and CT scan of the sinuses, for studying the ethmoidal slit and its relationship with the frontal sinus and anterior ethmoidal artery. MATERIALS AND METHODS: Retrospective study of 145 scans of the sinuses and 79 of the facial bones performed between 2012 and 2016. On each scan, the visibility of the ethmoidal slits, their length, their distance from the ethmoidal artery, and their relationship with the anterior and posterior wall of the frontal sinus were studied. RESULTS: The ethmoidal slit was better visualized on CT scans of the facial bone (58.2%) than on those of the sinuses (43.1%) (p = 0.02). The distance between the anterior ethmoidal artery and the anterior part of the cribriform plate was 9.3 mm for CT scans of the facial bone and 8.4 mm for CT scans of the sinuses. The theoretical risk of damaging the glabellar soft tissue and that of damaging the meninges during a frontal sinusotomy was evaluated, respectively, at 9.6% and 26.1% for CT scans of the facial bone, and at 6.2% and 21.5% for sinus scans. CONCLUSIONS: CT scans of the facial bone are better than CT scans of the sinuses for identifying ethmoidal slits and their distance from the canal of the anterior ethmoidal artery. The identification of these elements is relevant for the surgeon during frontal sinus surgery and makes it possible to assess the risk of damaging the glabellar soft tissue or meninges. Performing a CT scan of the facial bone seems preferable to that of a CT scan of the sinuses in certain pathological situations, such as cerebrospinal rhinorrhea or revision surgeries of the frontal sinus.
Asunto(s)
Hueso Etmoides , Seno Frontal , Humanos , Hueso Etmoides/diagnóstico por imagen , Hueso Etmoides/cirugía , Seno Frontal/diagnóstico por imagen , Seno Frontal/cirugía , Estudios Retrospectivos , Senos Etmoidales/diagnóstico por imagen , Senos Etmoidales/cirugía , Senos Etmoidales/irrigación sanguínea , Arteria OftálmicaRESUMEN
PURPOSE: Thiel's body preservation method allows the donor body to retain color and soft tissue that are similar to those of a living individual. Since its initial description, the technique has not been developed much. Here, we propose a simpler protocol applied to the head and neck, making the technique easier, cheaper, and more accessible to a greater number of medical schools. METHODS: The modified Thiel technique was applied to three heads separated from the body, followed by 6 h of perfusion and 6 weeks of fixation. This technique was compared with formalin (three heads) and freeze (three heads) preservations during academic training in head and neck surgery. Anatomical dissections included a parotid gland dissection, a submandibular gland dissection, an otologic and an endonasal dissection. Twelve surgeons blindly assessed the three types of preservations using a standardized questionnaire. RESULTS: The modified Thiel technique made possible better quality of dissection and tissue identification, with the exception of endonasal dissection. Concerning the endonasal dissection, the modified Thiel technique ranked best for smell, but all other criteria ranked lower than the freezing method. For the submandibular and parotid gland dissections, the modified Thiel technique was ranked best, with statistically significant differences (p < 0.002) for all items. The modified Thiel technique also ranked significantly better during otologic surgery regarding the quality of the skin/eardrum, bone, and muscle, and the smell. CONCLUSION: This study demonstrated that the modified Thiel technique is an embalming technique which improves the quality of head and neck surgical anatomy education.
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Embalsamiento , Formaldehído , Cadáver , Disección/métodos , Embalsamiento/métodos , Humanos , Facultades de MedicinaRESUMEN
PURPOSE: Pain is an increasing concern in the growing number of head and neck cancer survivors. This study aimed to analyze the 5-year prevalence of pain in French survivors of head and neck cancer and to identify associated factors. METHODS: Analyses were performed among 296 5-year cancer survivors diagnosed in 2010. Using multivariable logistic regressions, we studied the associations between pain and factors collected in the French representative national "vie après le cancer" (VICAN) survey. Eligible participants were aged from 18 to 82 years; patients' living conditions, socioeconomic characteristics, and medical data were collected. RESULTS: Pain was reported by 72.6% of the participants. In the multivariable analyses, decreasing level of physical activity was the only determinant of increased overall pain (OR= 2.77, CI= 1.48-5.17). The chronic pain prevalence was 62.3%. The main risk factors found were tumor localization in the oropharynx (OR= 2.49, CI= 1.27-4.88), education (at least a high school's degree) (OR= 0.33, CI= 0.13-0.9), and decreased physical activity (OR= 2.20, CI= 1.24-3.9). CONCLUSIONS: Five years after diagnosis, pain is a very frequent sequelae that has a significant impact on quality of life in head and neck cancer survivors. Reduced physical activity, a low level of education, and tumor localization in the oropharynx are factors associated with pain. IMPLICATIONS FOR CANCER SURVIVORS: Pain frequency and its impact on patients' lives imply that an adaptation must be made in terms of both pain diagnosis and management and the training of healthcare professionals. CLINICAL TRIAL REGISTRATION: This is not a clinical trial. ISP number: INSERM C11-63.
Asunto(s)
Supervivientes de Cáncer , Dolor Crónico , Neoplasias de Cabeza y Cuello , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Dolor Crónico/epidemiología , Dolor Crónico/etiología , Francia/epidemiología , Neoplasias de Cabeza y Cuello/complicaciones , Neoplasias de Cabeza y Cuello/epidemiología , Humanos , Persona de Mediana Edad , Calidad de Vida , Encuestas y Cuestionarios , Sobrevivientes , Adulto JovenRESUMEN
Minimal invasive surgery and reconstructive surgery tend to become the standard in France in the management of head and neck tumors. The use of endoscopic approaches (through endoscopic endonasal/transoral approaches±robot-assisted) instead of open surgery and the use of reconstructive surgery using autologous (flaps) or heterologous materials aim to reduce surgical morbidity by making-up for the loss of substance to restore the function. The impact of these substantial changes in surgical techniques has not been assessed with respect to postoperative radiotherapy practice. Endoscopic endonasal approaches result, however, in piecemeal resection, which, along the analysis of resection margins (a key prognostic factor), make the interpretation of the quality of resection more complex for radiation oncologists. The definition of tumour sub-volumes to be irradiated and doses to these sub-volumes then requires accurate histosurgical mapping and close multidisciplinary consultation between surgeons, pathologists, radiologists and radiation oncologists. Similarly, the increasing use of various types of flaps (of soft tissue or bone flaps), adapted to the patient and tumor anatomy, is associated with substantial modifications to the operating bed. The delineation of tumour volumes in postoperative radiotherapy is made more complex. Tremendous multidisciplinary efforts should now be initiated to fully take advantage of surgical advances and to further optimize the therapeutic index by making radiotherapy also less toxic, i.e. "mini-morbid".