Impact of Neck Dissection in Head and Neck Squamous Cell Carcinomas of Unknown Primary.

PURPOSE: Management of head and neck cancers of unknown primary (HNCUP) combines neck dissection (ND) and radiotherapy, with or without chemotherapy. The prognostic value of ND has hardly been studied in HNCUP. METHODS: A retrospective multicentric study assessed the impact of ND extent (adenectomy, selective ND, radical/radical-modified ND) on nodal relapse, progression-free survival (PFS) or survival, taking into account nodal stage. RESULTS: 53 patients (16.5%) had no ND, 33 (10.2%) had lymphadenectomy, 116 (36.0%) underwent selective ND and 120 underwent radical/radical-modified ND (37.3%), 15 of which received radical ND (4.7%). With a 34-month median follow-up, the 3-year incidence of nodal relapse was 12.5% and progression-free survival (PFS) 69.1%. In multivariate analysis after adjusting for nodal stage, the risk of nodal relapse or progression was reduced with lymphadenectomy, selective or radical/modified ND, but survival rates were similar. Patients undergoing lymphadenectomy or ND had a better PFS and lowered nodal relapse incidence in the N1 + N2a group, but the improvement was not significant for the N2b or N2 + N3c patients. Severe toxicity rates exceeded 40% with radical ND. CONCLUSION: In HNCUP, ND improves PFS, regardless of nodal stage. The magnitude of the benefit of ND does not appear to depend on ND extent and decreases with a more advanced nodal stage.

[Anaplastic thyroid carcinoma : new therapeutic approaches]. / Carcinome anaplasique de la thyroïde : nouvelles approches thérapeutiques.

Anaplastic thyroid cancer (ATC) is among the most aggressive cancers with a median overall survival of 4 months and a disease-specific mortality of close to 100%. As soon as the diagnosis is suspected or established, urgent referral to an experienced multidisciplinary center is imperative. Chemotherapy has limited efficacy. Molecular analyses, together with the availability of novel targeted therapies and immunotherapies, now permit to improve outcomes. In particular, targeted therapy with dabrafenib and trametinib is indicated as first-line therapy for BRAF V600E-mutated ATC.

Le cancer anaplasique de la thyroïde (CAT) compte parmi les cancers les plus agressifs avec une survie médiane de 4 mois et une mortalité spécifique à la maladie proche de 100 %. Dès que le diagnostic est suspecté ou établi, une orientation urgente vers un centre multidisciplinaire expérimenté est essentielle. La chimiothérapie a une efficacité limitée. Les analyses moléculaires, ainsi que la disponibilité de nouvelles thérapies ciblées et d'immunothérapies, permettent désormais d'améliorer les résultats. En particulier, le CAT avec mutation BRAF V600E bénéficie d'une combinaison de thérapies ciblées par dabrafénib et tramétinib en traitement de première ligne.

Analysis of Radiation Dose/Volume Effect Relationship for Anorectal Morbidity in Children Treated for Pelvic Malignancies.

PURPOSE: To examine dose-volume effect relationships for anorectal morbidity in children treated with image-guided brachytherapy for pelvic tumors. METHODS AND MATERIALS: Medical records of all consecutive children with pelvic tumors treated in our center and receiving image-guided pulsed-dose-rate brachytherapy with or without external beam radiation therapy (EBRT) between 2005 and 2019 were reviewed. The effect of the minimal doses to the most exposed 0.5 cm3, 1 cm3, and 2 cm3 of the anorectum (respectively: D0.5cm3, D1cm3, and D2cm3), total reference air kerma (TRAK), and volume of 100% isodose was examined for anorectal toxicities. RESULTS: Seventy-eight consecutive children were included. Median age was 2.9 years (range, 0.8-14.9 years). Most of the tumors were bladder or prostate (67%) or vaginal (22%) rhabdomyosarcoma. Six patients received EBRT in addition to brachytherapy. Median follow-up was 21.3 months. At last follow-up, 30 children (38%) had experienced Common Terminology Criteria for Adverse Events version 5 grade ≥1 acute or late anorectal events: 24% had grade 1 events, 7.7% had grade 2 events, and 6.4% had grade 3 events. No toxicity greater than grade 3 was observed (eg, fistula or stricture). In univariate analysis, the D0.5cm3 and D1cm3 were significant for probability of grade 1 to 3 (P = .009 and P = .017, respectively) and grade 2 to 3 anorectal morbidity (P = .007 and P = .049, respectively). There was no significant correlation for D2cm3 (P = .057 for grade 1-3; P = .407 for grade 2-3). A 10% probability (95% confidence interval, 4%-20%) for anorectal toxicity of grade 2 or greater was reached for a D0.5cm3 = 52 Gy. The age, EBRT use, TRAK, and treated volume values were not significant. CONCLUSIONS: To our knowledge, this study is the first to show a significant dose-volume effect relationships for anorectal morbidity in children undergoing treatment with brachytherapy. Integrating these data into brachytherapy treatment planning could help to optimize the therapeutic index in these young patients.

Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells.

BACKGROUND: Combining radiotherapy (RT) with immuno-oncology (IO) therapy (IORT) may enhance IO-induced antitumor response. Quantitative imaging biomarkers can be used to provide prognosis, predict tumor response in a non-invasive fashion and improve patient selection for IORT. A biologically inspired CD8 T-cells-associated radiomics signature has been developed on previous cohorts. We evaluated here whether this CD8 radiomic signature is associated with lesion response, whether it may help to assess disease spatial heterogeneity for predicting outcomes of patients treated with IORT. We also evaluated differences between irradiated and non-irradiated lesions. METHODS: Clinical data from patients with advanced solid tumors in six independent clinical studies of IORT were investigated. Immunotherapy consisted of 4 different drugs (antiprogrammed death-ligand 1 or anticytotoxic T-lymphocyte-associated protein 4 in monotherapy). Most patients received stereotactic RT to one lesion. Irradiated and non-irradiated lesions were delineated from baseline and the first evaluation CT scans. Radiomic features were extracted from contrast-enhanced CT images and the CD8 radiomics signature was applied. A responding lesion was defined by a decrease in lesion size of at least 30%. Dispersion metrices of the radiomics signature were estimated to evaluate the impact of tumor heterogeneity in patient's response. RESULTS: A total of 94 patients involving multiple lesions (100 irradiated and 189 non-irradiated lesions) were considered for a statistical interpretation. Lesions with high CD8 radiomics score at baseline were associated with significantly higher tumor response (area under the receiving operating characteristic curve (AUC)=0.63, p=0.0020). Entropy of the radiomics scores distribution on all lesions was shown to be associated with progression-free survival (HR=1.67, p=0.040), out-of-field abscopal response (AUC=0.70, p=0.014) and overall survival (HR=2.08, p=0.023), which remained significant in a multivariate analysis including clinical and biological variables. CONCLUSIONS: These results enhance the predictive value of the biologically inspired CD8 radiomics score and suggests that tumor heterogeneity should be systematically considered in patients treated with IORT. This CD8 radiomics signature may help select patients who are most likely to benefit from IORT.

Hypnosedation for endocavitary uterovaginal applications: A pilot study.

PURPOSE: Implantations for uterovaginal brachytherapy are usually performed under general or spinal anesthesia, which are not without risk. As it is a rather short procedure and since postoperative pain is minimal, hypnosedation was proposed to selected patients requiring endocavitary applications as part of their routine treatment. METHODS AND MATERIALS: Consecutive patients requiring intracavitary uterovaginal brachytherapy from January to October 2019 were included if they accepted the procedure. A premedication was systematically administered. Hypnosedation was based on an Ericksonian technique. The procedure was immediately interrupted if the patient requested it, in cases of extreme anxiety or pain. Procedure was in that case rescheduled with a "classical" anesthesia technique. RESULTS: A total of 20 patients were included. Four patients had to be converted toward a general anesthesia: one because of a fibroma on the probe's way and three young patients with a very anteverted/retroverted uterus that was painful at every mobilization. Mean and maximum pain scores during implant were 2.9/10 and 5.1/10, respectively. The most painful maneuver was cervical dilation for 45% of the patients, followed by mold insertion in 40% of cases. About 85% of the patients declared that hypnosis helped them relax; 90% of the patients would recommend the technique. No procedure-related complication occurred. CONCLUSION: With a 70% success rate (correct implant with mean pain and anxiety scores < 5), one can conclude that uterovaginal brachytherapy implantation under hypnosedation is feasible and received a high satisfaction rate from the patients. This technique may reduce overall treatment time in a context of difficult access to the OR and to anesthesiologists, while reducing anesthetic drugs resort and postoperative nausea.

Unilateral or bilateral irradiation in cervical lymph node metastases of unknown primary? A retrospective cohort study.

INTRODUCTION: Patients with cervical lymphadenopathy of unknown primary carcinoma (CUP) usually undergo neck dissection and irradiation. There is an ongoing controversy regarding the extent of nodal and mucosal volumes to be irradiated. We assessed outcomes after bilateral or unilateral nodal irradiation. METHODS: This retrospective multicentre study included patients with CUP and squamous cellular carcinoma who underwent radiotherapy (RT) between 2000 and 2015. RESULTS: Of 350 patients, 74.5% had unilateral disease and 25.5% had bilateral disease. Of 297 patients with available data on disease and irradiation sides, 61 (20.5%) patients had unilateral disease and unilateral irradiation, 155 (52.2%), unilateral disease and bilateral irradiation and 81 (27.3%), bilateral disease and bilateral irradiation. Thirty-four (9.7%) and 217 (62.0%) patients received neoadjuvant and/or concomitant chemotherapy, respectively. Median follow-up was 37 months. Three-year local, regional, locoregional failure rates and CUP-specific survival were 5.6%, 11.7%, 15.0% and 84.7%, respectively. In patients with unilateral disease, the 3-year cumulative incidence of regional/local relapse was 7.7%/4.3% after bilateral irradiation versus 16.9%/11.1% after unilateral irradiation (hazard ratio = 0.56/0.61, p = 0.17/0.32). The cumulative incidence of CUP-specific deaths was 9.2% after bilateral irradiation and 15.5% after unilateral irradiation (p = 0.92). In multivariate analysis, mucosal irradiation was associated with better local control, whereas no neck dissection, ≥N2b and interruption of RT for more than 4 days were associated with poorer regional control. Toxicity was higher after bilateral irradiation (p < 0.05). No positron-emission tomography-computed tomography, largest node diameter, ≥N2b, neoadjuvant chemotherapy and interruption of RT were associated with poorer cause-specific survival. CONCLUSION: Bilateral nodal irradiation yielded non-significant better nodal and mucosal control rates but was associated with higher rates of severe toxicity.