Introduction. Due to variety of morphological subtypes and poor clinical response, comprehensive molecular profiling for salivary gland cancers become a part of treatment strategy for chemotherapy-resistant cases. Tumors of the salivary glands include more than 20 histological types distinguished by their biological characteristics, response to therapy, and prognosis. The search for specific therapeutically significant markers and mutations for various histological types of salivary gland tumors may allow the development of a diagnostic algorithm and improve patient treatment results.Aim. To search for therapeutically significant molecular and genetic targets and immunohistochemical markers in various histological types of malignant salivary gland tumors.Materials and methods. We analyzed data on 280 patients with unresectable recurrent and metastatic salivary gland cancer to identify the main characteristic therapeutically significant immunohistochemical (androgen receptor (AR), epidermal growth factor receptor type 2 (HER2neu), epidermal growth factor receptor (EgfR), programmed cell death receptor 1 (pD-L1) (CpS), сD117, estrogen receptor (ER), progesterone receptor (pR), pan-TRk) and molecular genetic targets (ALK, BRAF, ERBB2, KIT, MET, RET, ROS1, SMO, AR, HRAS, PIK3CA, PDGFRA, NTRK1-3) depending on the histological subtype of the tumor.Results. Based on the results obtained, in comparison with previous studies, a greater diversity of therapeutically significant mutations, fusions and immunohistochemical markers was revealed for various histological types of tumors. Interestingly, increased expression of AR was detected not only in salivary duct carcinoma, but also in carcinoma ex pleomorphic adenoma, adenocarcinoma not otherwise specified, myoepithelial, mucoepidermoid, adenoid cystic, acinic cell, polymorphous adenocarcinomas. ETV6-NTRK3 gene fusions in addition to secretory carcinoma were detected in mucoepidermoid and salivary duct carcinomas. mutations and fusions in the RET gene have been identified in ductal and mucoepidermoid carcinomas, as well as adenocarcinoma not otherwise specified.Conclusion. The results of the study allow to expand the group of patients for molecular genetic and IHC testing in order to individualize therapy.

Nasopharyngeal carcinoma is a rare pathology. It develops in the nasopharyngeal mucosa and is characterized by aggressive (recurrent and metastatic) progression. Due to complicated location, this disease is often diagnosed at late stages and requires systemic therapy. Due to the rareness of nasopharyngeal carcinoma, until recently there were no studies on modern drug therapy of this pathology with high evidence level.Aim. To describe the capabilities and mechanism of action of camrelizumab in nasopharyngeal carcinoma. The results of studies investigating the mechanism of action of camrelizumab were analyzed. The effectiveness of this drug in progression of nasopharyngeal cancer with previous chemotherapy and in combination with chemotherapy as the 1st line treatment of recurrent and / or metastatic process was evaluated. Based on the phase II trial results, the use of camrelizumab in patients with disease progression during standard chemotherapy allows to achieve progression-free survival of 8.5 months. Data obtained in the phase III trial demonstrated clinical benefit of adding this drug to standard chemotherapy in the 1st line therapy of recurrent and / or metastatic nasopharyngeal carcinoma: median progressionfree survival significantly increased from 6.9 to 9.7 months.Therefore, camrelizumab is a modern highly effective immunotherapeutic drug designed to treat patients with nasopharyngeal carcinoma.

Introduction: Despite the fact that highly differentiated thyroid cancer is included in the group of malignant neoplasms with a favorable prognosis, data on the high frequency and recurrence of relapses are reported. The presence of metastatic lymph nodes in HDTC increases the risk of regional relapse by up to 27 %. According to the literature, the factors that increase the risk of recurrence are: histological type, stage, depth of extrathyroid invasion, the presence of metastatic lymph nodes, age, and the volume of primary surgical intervention. Lateral neck dissection should be performed in patients with morphologically verified metastatic thyroid cancer, but there is still no clear consensus on the volume of dissection. Aim: Assessment of factors affecting the risk of regional recurrence in the lateral neck tissue and the localization of recurrence. Materials and methods: The study included 56 patients with HDTC, in whom metastatic lateral neck nodes were identified and verified. All patients previously underwent unilateral or bilateral neck lymph node dissection in various institutions. During the period of dynamic follow-up, these patients revealed regional recurrences in the lateral tissue of the neck. The patients were observed and treated for recurrence at the N. N. Blokhin National Medical Research Center of Oncology of the Ministry of Health of Russia. Results: Age over 55 years is a prognostically significant factor affecting the frequency of regional relapse in the lateral neck tissue (p = 0.002). The presence of metastatic nodes in the lateral tissue of the neck at the initial treatment is a prognostically significant factor that increases the risk of regional recurrence in the lateral tissue of the neck (p = 0.017). According to the results of a single-factor analysis, a statistically significant effect of the stage on the risk of regional relapses in the lateral neck tissue was noted (p = 0.014). In 35.7 % of cases, recurrent nodes were localized in the level V. Conclusion: Main risk factors for relapse are clinico-morphological, such as age, aggressive type of HDTC, stage of the disease, N1b status after primary surgery, as well as technical defects during primary surgical treatment.

Recurrent and metastatic head and neck squamous cell carcinoma is a hard-to-treat pathology. median overall survival for standard chemotherapy regimens does not exceed 11 months. One of the factors decreasing treatment effectivenessis frequency of severe adverse events which are observed in every 2nd patient during standard therapy regimens. moreover, even if notable tumor regression is achieved, this effect is transient. Development of immunotherapy drugs, namely pembrolizumab, helps solve these problems. Clinical trials and real-world use of the drug show that in the 1st and 2nd therapy lines for recurrent and metastatic head and neck squamous cell carcinoma, pembrolizumab allows to achieve persistent treatment response, increase overall survival, and decrease the frequency of adverse events.

The study objective: to assess the diagnostic value of measuring the concentration of thyroglobulin (Tg) in the washout fluid of the fine needle aspiration (FNA) for the detection of well-differentiated thyroid cancer regional metastases.Material and Methods. The study included 64 patients with well-differentiated thyroid cancer. Ultrasound examination revealed 71 enlarged regional lymph nodes. The patients underwent simultaneous FNA cytology examination of lymph nodes and the study of Tg concentration in the washout fluid of the needle aspiration. Regional lymph node metastases were verified in 38 patients. These patients underwent surgery. Histological examination of surgical specimens was performed in 43 out of 71 cases.Results. The sensitivity, specificity, and accuracy of the FNA biopsy and the study of the concentration of thyroglobulin in the in the washout fluid of FNA were 88.5 %, 56.3 %, 76.2 % and 100 %, respectively. The rate of false-positive results of thyroid FNA biopsy was 16 %. The optimal cutoff value for FNA-Tg measurement was 4 g/ml. This made it possible to increase the sensitivity and specificity of the method to 100 %. It was found that the presence of circulating antibodies to Tg in the blood serum had no effect on the diagnostic value of FNA-Tg measurement (p=0.421). There were no statistically significant differences in the levels of thyroglobulin in the in the washout fluid of FNA between patients with Tg concentration above and below the cutoff values (3.9 [0.47; 39.9] ng/ ml vs 12.3 [0.57; 294.8] ng/ml).

Introduction . Thyroid cancer is the most common malignant tumor of the endocrine system and comprises 33 % of malignant neoplasms of the head and neck. first echelon lymph nodes affected by this pathology are located in the central area of the neck. The metastatic process further advances into the lymph nodes in the lateral tissues of the neck. Currently, there is no consensus on the effectiveness of prophylactic central lymph node dissection and no conclusive criteria determining the risk of recurrence in the central zone. Aim. The assessment of factors influencing the risk of regional recurrence in the central zone. Materials and methods. The study included 30 patients with highly differentiated thyroid cancer, in whom metastatic nodes in the central zone were identified and verified during primary treatment. All patients previously underwent unilateral or 2-sided central lymph node dissection in various institutions. During the period of dynamic observation, these patients revealed regional recurrence in the central zone. patients were observed and treated for recurrence at the National medical Research Center of Oncology named after N.N. Blokhin of the ministry of Health of Russia. Results. primary surgical treatment in a specialized oncological institution was performed in 21 (70 %) patients, in a general surgical medical institution – in 7 (23.3 %), in an endocrinological institution – in 2 (6.7 %) patients. when assessing the influence of the morphological type and variant of thyroid cancer on the risk of developing regional recurrence, no statistical significance was found. No statistically significant factors were found in the analysis of the influence of characteristics of the primary tumor, such as tumor size, multifocal lesion, vascular invasion, extrathyroidal spread, on the risk of regional recurrence. In 16 (53.3 %) patients, recurrence occurred in the paratracheal zone of the ipsilateral side, in 7 (23.3 %) patients in the paratracheal zone of the contralateral side, bilateral lesions were observed in 2 (6.67 %) cases. 3 (10 %) patients were diagnosed with transient parathyroid insufficiency, 1 (3.3 %) – permanent parathyroid insufficiency, 1 (3.3 %) – hematoma in the area of the postoperative wound, patient, 2 (6.6 %) – injury to the recurrent laryngeal nerve. Conclusion . Residual metastatic lymph nodes after previous surgical treatment are the reason for performing a second operation, which carries both the risks of postoperative complications and the psychological burden on the patient. Thus, an adequate and radically performed primary surgical intervention is the key to reducing regional recurrences.

The article presents a draft of clinical recommendations for the diagnosis and treatment of differentiated thyroid cancer in adult patients, which provides a modern examination algorithm, discusses the basic principles of laboratory, instrumental diagnostics and treatment approaches.

Introduction. Thyroid cancer is one of the most common malignant neoplasms of the endocrine system. well-differentiated thyroid cancer constitutes about 90 % of all malignant tumors of the thyroid gland. Despite growing morbidity and high incidence of this pathology, in case of timely diagnosis and treatment well-differentiated thyroid cancer has favorable prognosis. Aim. using clinical examples, to demonstrate the possibility of thyroglobulin measurement in needle washouts of fineneedle aspiration biopsy in the detection of cervical metastases of highly differentiated thyroid cancer. Materials and methods. five patients (2 patients with combined oncological pathology, 2 patients with nodes in the thyroid gland, 1 patient after a thyroidectomy) with cervical adenopathy measured the level of thyroglobulin in the wash out fluid of lymph-nodes biopsy using the immunoradiometric method using the commercial kits of the Institute of Isotopes-IRmA (Hungary). Results. Cervical metastases of highly differentiated thyroid cancer were detected or excluded by the determination of fine-needle aspiration biopsy in patients with non-informational cytological studies. The determination of fineneedle aspiration biopsy is a useful diagnostic method in the differential diagnosis of cervical metastases in patients who have other morphological forms of cancer in addition to well-differentiated thyroid cancer, as well as for the differential diagnosis of cervical adenopathy in patients with a history of highly differentiated thyroid cancer. Conclusion. Determination of thyroglobulin level in puncture needle washout is a simple and useful diagnostic method for differential diagnosis of metastases in lymph nodes of the neck in patients with several morphological forms of malignant tumors.

Introduction. Treatment of the oral cavity is an important problem of current oncology due to high morbidity and mortality reaching 43 % in 5-year period after diagnosis. frequency of positive resection margins is 30 % of cases which partially explains unsatisfactory results of therapy of this pathology and promotes investigation of methods increasing radicalness of surgical treatment of the primary lesion.The study objective is to evaluate the effectiveness of fluorescent visualization with 5-aminolevulinic acid for assessment of radicalness of surgical intervention in cancer of the oral mucosa.Materials and methods. In the study, evaluation of the effectiveness of 5-aminolevulinic acid for intraoperative determination of margins of squamous cell carcinoma of the oral mucosa (n = 36) was performed.Results. Comparison of intraoperative results using 5-aminolevulinic acid and results of histological examination showed that the difference in mean distances from the tumor edge to resection margin was 0.07 mm (95 % confidence interval 2.2905-2.4334) and wasn't statistically significant (p = 0.9519). Sensitivity of intraoperative fluorescent visualization with 5-aminolevulinic acid in diagnosis of resection margins was 100 %, specificity was 92.3 %, accuracy was 92.9 %, effectiveness was 96.1 %. Optimal effect of the fluorescent technique was achieved in patients with exophytic and mixed types of tumor growth without previous treatment.Conclusion. Method of intraoperative fluorescent visualization with 5-aminolevulinic acid showed high effectiveness (96.1 %) and can be recommended for intraoperative assessment of tumor margins and increase of radicalness of surgical treatment of cancer of the oral mucosa.

Background. The implementation of tyrosine kinase inhibitors into clinical practice improved treatment outcomes in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC). Lenvatinib is recommended as a first-line drug for these patients. The study objective is to analyze clinical experience with lenvatinib in patients with RR-DTC in the Russian Federation. Materials and methods. The data from 18 clinical sites in Russia was analyzed for the period December 2015 and September 2019. Seventyseven patients with histologically verified DTC, proven resistance to radioactive iodine therapy, and tumor progression (according to the Response Evaluation Criteria In Solid Tumors 1.1 criteria) were included in the study. Results.Median progression-free survival in patients included into analysis (n = 72) was 26.1 months. In patients who responded to therapy (including those with partial and complete response), median progression-free survival reached 36.2 months, which is higher than that reported in the updated results of the SELECT study (33.1 months). Lenvatinib-associated adverse events (AEs) were observed in 87 % of patients. Severe AEs were registered in 18.2 % of participants. In 6.5 % of cases, AEs lead to lenvatinib cessation; in 74 % of cases, AEs required dose reduction.Conclusion. Our findings suggest high efficacy and good tolerability of lenvatinib in patients with RR-DTC in routine clinical practice in the Russian Federation.

The study objective is to perform retrospective analysis of the efficacy and safety of vandetanib for metastatic and non-resectable medullary thyroid cancer in routine clinical practice. Materials and methods. We analyzed treatment outcomes in 46 patients treated with vandetanib. We also evaluated progression-free survival, overall survival, time to progression, and frequency of adverse events. Results. At a median follow-up time of 27.4 months (range: 2.5–106.5 months) and median duration of vandetanib therapy of 21 months, disease progression was registered in 32.6 % of cases, whereas stable disease was observed in 28.3 % of cases and 8.7 % of study participants demonstrated partial response. One patient had complete response to treatment. Almost one-third of patients (28.2 %) died, including 2 individuals whose death was not associated with cancer. The one-year and three-year progression-free survival rates were 67.3 % and 33.3 %, respectively; the two-year and five-year overall survival rates were 82.4 % and 29.4 %, respectively. The efficacy of therapy was confirmed by a 79.4 % decrease in the serum level of calcitonin after treatment initiation. Side effects were observed in 33.9 % of patients (primarily skin and gastrointestinal toxic reactions) and were easily managed in most of the cases. Eight individuals (17.4 %) required cessation of vandetanib due to adverse events. Conclusion. Our findings suggest high efficacy and acceptable safety profile of vandetanib in the treatment of progressive locally advanced non-resectable and disseminated medullary thyroid cancer

The study objective : using a clinical example to demonstrate possibilities of single photon emission computerized tomography (SPECT) in combination with computed tomography (CT) in identifying latent bone metastases, taking into account the dynamics growth of serum basal calcitonin. Materials and methods . Patient S., 60 years old, visited N.N. Blokhin National Medical Research Center of Oncology for consultation on multiple lung metastases of cancer of unknown primary. Results. Taking into account basal calcitonin level, immunohistochemistry, ultrasound investigation andfine-needle aspiration biopsy of the node in the right thyroid lobe a diagnose of medullary thyroid cancer was made. CT revealed multiple metastases in both lungs. Specialist erformed thyroidectomy with central lymphadenectomy and facial neck dissection on both sides. During next four months basal calcitonin level increased twice. Control contrast CT lung screening showed the growth of previously identified metastases and the appearance of multiple new ones. Bone scan showed focuses of increased radio-pharmaceutical accumulation in the area of 7 h left rib, left iliac wing, in the left bones of cranial vault, in C 7 , Th 6 , Th 9 , Th I2 vertebrae and right foot bones. Additional examination using SPECT/CT (from the skull base to the hip joints) revealed metastases in corpuses of Th 9 , Th I2 vertebrae and the left iliac wing, and suspicion for metastasis in 7 h left rib. Magnetic resonance imaging (MRI) confirmed metastasis in Th 9 , Th I2 , L 3 vertebral bodies and in the left iliac wing. Conclusion. Conclusion . In this clinical example, SPECT/CT allowed to correctly detect metastases in both Th 9 and Th I2 vertebrae while bone scan was questionable, and MRI showed an additional damage of L 3 vertebra. Changes in the 7 h left rib could not be verified using CT, although this changes may be an emerging metastasis. Obviously, extensive use of radiation methods does not guarantee complete identification of all pathological focuses, it therefore allows assessing the prevalence of the pathological process. It is crucially important to control calcitonin level in these patients, since its rapid growth allowed suspecting additional distant metastases.

The study objective : using a clinical example to demonstrate possibilities of single photon emission computerized tomography (SPECT) in combination with computed tomography (CT) in identifying latent bone metastases, taking into account the dynamics growth of serum basal calcitonin. Materials and methods . Patient S., 60 years old, visited N.N. Blokhin National Medical Research Center of Oncology for consultation on multiple lung metastases of cancer of unknown primary. Results. Taking into account basal calcitonin level, immunohistochemistry, ultrasound investigation andfine-needle aspiration biopsy of the node in the right thyroid lobe a diagnose of medullary thyroid cancer was made. CT revealed multiple metastases in both lungs. Specialist erformed thyroidectomy with central lymphadenectomy and facial neck dissection on both sides. During next four months basal calcitonin level increased twice. Control contrast CT lung screening showed the growth of previously identified metastases and the appearance of multiple new ones. Bone scan showed focuses of increased radio-pharmaceutical accumulation in the area of 7 h left rib, left iliac wing, in the left bones of cranial vault, in C 7 , Th 6 , Th 9 , Th I2 vertebrae and right foot bones. Additional examination using SPECT/CT (from the skull base to the hip joints) revealed metastases in corpuses of Th 9 , Th I2 vertebrae and the left iliac wing, and suspicion for metastasis in 7 h left rib. Magnetic resonance imaging (MRI) confirmed metastasis in Th 9 , Th I2 , L 3 vertebral bodies and in the left iliac wing. Conclusion. Conclusion . In this clinical example, SPECT/CT allowed to correctly detect metastases in both Th 9 and Th I2 vertebrae while bone scan was questionable, and MRI showed an additional damage of L 3 vertebra. Changes in the 7 h left rib could not be verified using CT, although this changes may be an emerging metastasis. Obviously, extensive use of radiation methods does not guarantee complete identification of all pathological focuses, it therefore allows assessing the prevalence of the pathological process. It is crucially important to control calcitonin level in these patients, since its rapid growth allowed suspecting additional distant metastases.

IMPORTANCE:Locoregionally advanced head and neck squamous cell cancer (HNSCC) is treated curatively; however, risk of recurrence remains high among some patients. The ERBB family blocker afatinib has shown efficacy in recurrent or metastatic HNSCC. OBJECTIVE:To assess whether afatinib therapy after definitive chemoradiotherapy (CRT) improves disease-free survival (DFS) in patients with HNSCC. DESIGN, SETTING, AND PARTICIPANTS:This multicenter, phase 3, double-blind randomized clinical trial (LUX-Head & Neck 2) studied 617 patients from November 2, 2011, to July 4, 2016. Patients who had complete response after CRT, comprising radiotherapy with cisplatin or carboplatin, with or without resection of residual disease, for locoregionally advanced high- or intermediate-risk HNSCC of the oral cavity, hypopharynx, larynx, or oropharynx were included in the study. Data analysis was of the intention-to-treat population. INTERVENTIONS:Patients were randomized (2:1) to treatment with afatinib (40 mg/d) or placebo, stratified by nodal status (N0-2a or N2b-3) and Eastern Cooperative Oncology Group performance status (0 or 1). Treatment continued for 18 months or until disease recurrence, unacceptable adverse events, or patient withdrawal. MAIN OUTCOMES AND MEASURES:The primary end point was DFS, defined as time from the date of randomization to the date of tumor recurrence or secondary primary tumor or death from any cause. Secondary end points were DFS at 2 years, overall survival (defined as time from the date of randomization to death), and health-related quality of life. RESULTS:A total of 617 patients were studied (mean [SD] age, 58 [8.4] years; 528 male [85.6%]). Recruitment was stopped after a preplanned interim futility analysis on July 4, 2016, on recommendation from an independent data monitoring committee. Treatment was discontinued. Median DFS was 43.4 months (95% CI, 37.4 months to not estimable) in the afatinib group and not estimable (95% CI, 40.1 months to not estimable) in the placebo group (hazard ratio, 1.13; 95% CI, 0.81-1.57; stratified log-rank test P = .48). The most common grade 3 and 4 drug-related adverse effects were acneiform rash (61 [14.8%] of 411 patients in the afatinib group vs 1 [0.5%] of 206 patients in the placebo group), stomatitis (55 [13.4%] in the afatinib group vs 1 [0.5%] in the placebo group), and diarrhea (32 [7.8%] in the afatinib group vs 1 [0.5%] in the placebo group). CONCLUSIONS AND RELEVANCE:This study's findings indicate that treatment with afatinib after CRT did not improve DFS and was associated with more adverse events than placebo in patients with primary, unresected, clinically high- to intermediate-risk HNSCC. The use of adjuvant afatinib after CRT is not recommended. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT01345669.

Medullary thyroid cancer is a rare tumor. Due to variability of its biological behavior, treatment of this tumor often is a complicated problem. Clinicians have difficulties with determination of indications for prescription of tyrosine kinase inhibitors. Prescription should be based on scru-tinous monitoring of the patients and consideration of all factors: level of tumor markers, patient’s state, and data form visual examinations.

Medullary thyroid cancer (MTC) is a rare disorder that accounts for approximately 1.7 % of all thyroid malignancies. MTC is usually detected at early stages; however, approximately 10–15 % of patients are diagnosed with locally advanced MTC and distant metastases. Treatment of such patients is challenging due to biological characteristics of the disease and very few effective treatment approaches available. The investigation of mechanisms of carcinogenesis, as well as advances in pharmacology, allowed the development of a new group of targeted drugs, namely tyrosine kinases, which efficacy against progressive unresectable locally advanced or metastatic MTC has been demonstrated in multiple clinical trials. Vandetanib has been registered for MTC treatment in the Russian Federation. MTC is very rare, thus, each case of vandetanib use for its treatment is particularly interesting. Moreover, since the approval of this drug in 2011 by the U. S. Food and Drug Administration (FDA), new data on the clinical use of vandetanib have been accumulated. Importantly, clinical trials are usually well designed and conducted in near-ideal conditions, whereas the real conditions can be different and patients may have individual characteristics. Therefore, the aim of this study was to update the information on the efficacy and safety of vandetanib by retrospective analysis of available publications and to report a case of MTC treated with vandetanib.

Reconstruction of head and neck defects after surgery for cancer remains challenging. The choice of the reconstruction technique depends on the tumor size and localization, type of the defect, patient’s age, concomitant diseases, and disease prognosis. Surgeons have currently a broad range of material for reconstructive surgery, from free flaps to revascularized flaps. Microsurgical reconstruction has made a revolution in treatment of patients with complex head and neck defects. However, the use of this technique may not be advisable for some patients. The search for new techniques is needed to improve functional and aesthetic results and reduce traumatism without compromising oncologic outcomes. Thirty-six patients underwent surgery with reconstruction using the submental island flap, a new alternative in the reconstruction of various head and neck defects. The graft was taken after making a neck incision for neck lymph node dissection. A few patients develop total and marginal necrosis of the graft. Short- and long-term results showed no worsening of oncologic outcomes in the selected group of patients.

N.N. Blokhin National Medical Research Oncology Center, Ministry of Health of Russia; 24 Kashirskoe Shosse, Moscow 115478, Russia Positron emission tomography (PET) with 18F-fluorodeoxyglucose is included in the algorithm of examination and monitoring in patients with radioactive iodine-refractory differentiated thyroid cancer. In assessing the effectiveness of targeted therapy, criteria based on the values of SUVmax (standardized uptake value) in metastases are used. The article shows the results of PET studies in a patient with radioactive iodine-refractory papillary thyroid cancer treated with sorafenib. The dynamics of tumor activity of metastases by different quantitative indicators were evaluated.

6001 Background: Locally advanced HNSCC is treated curatively, but recurrence is common. In HNSCC, EGFR is richly expressed and EGFR inhibition is validated treatment (tx); the ErbB family blocker afatinib (A) showed efficacy in recurrent/metastatic disease. This Phase III trial assessed if A after definitive CRT improves disease-free survival (DFS). Methods: Eligible pts had complete response after CRT ≥66 Gy (or equivalent) with concurrent cisplatin or carboplatin but not prior EGFR inhibition, for HNSCC of oral cavity, hypopharynx, larynx, or oropharynx with >10 pack years (pk yrs) tobacco use. Pts were stratified by ECOG PS (0/1) and nodal stage (N0–2a/N2b–3), and randomized 2:1 to A 40 mg/d or placebo (P); tx continued for 18 m if tolerated, or until disease recurrence. The primary endpoint was DFS. Results: Of 669 pts planned, 617 were randomized; A 411, P 206. Median age was 58 yrs; 86% were male; 65% ECOG PS 0; most had smoked (A/P ex-smoker: 66/72%; current: 28/22%). Subsites (A/P) were: oropharynx 53/54%; hypopharynx 21/23%; larynx 18/12%; oral cavity 9/10%. The majority had T3 or 4 (A/P 70/68%) and N2 disease (67/63%). Accrual was halted for futility on independent DMC recommendation: at a pre-planned interim analysis (40% of DFS events), median DFS was A 43.4 m vs P not reached (NR; HR 1.13 [95% CI 0.81–1.57], p=0.48); the Table shows key subgroups. Median treatment duration was A 300.0 d, P 455.5 d. Recurrence was A 23%, P 23%. Dose reduction of A was required in 53% (mostly due to diarrhea, stomatitis). Tx was discontinued due to AEs in A 15%, P 4%. Conclusions: A after CRT did not improve DFS vs P. Subgroup analyses were underpowered to provide definitive conclusions. Harrington and Cohen contributed equally. Clinical trial information: NCT01345669. [Table: see text]

Well-differentiated thyroid carcinoma (WDTC) comprises > 90 % of all cases of thyroid cancer. In 10–15 % of patients, distant metastases are detected which significantly worsen the prognosis. Radioactive iodine therapy remains the main type of treatment of this patient group, but for patients with so-called radioactive iodine-refractory WDTC the prognosis is very poor. After successful phase III studies, several drugs from the group of multikinase inhibitors are being used in clinical practice for treatment of radioactive iodine-refractory WDTC, for example lenvatinib. In this article, we present a group of patients with radioactive iodine-refractory WDTC who received lenvatinib therapy.