Clinical application of supraclavicular flap for head and neck reconstruction.

PURPOSE: To assess the efficacy and clinical application of a supraclavicular flap for head and neck reconstruction. METHOD: A pedicled supraclavicular flap was used on 26 patients at Sun Yat-Sen University Cancer Center between July 2017 and November 2018, including 16 cases with oral cancer defects, 7 cases with laryngeal cancer and hypopharyngeal carcinoma defects, 1 case with parotid gland cancer defects, 1 case with external auditory canal cancer defects, and 1 case with tracheal esophageal fistula. The time required to harvest the flap, the amount of intraoperative blood loss, the duration of postoperative drainage tube placement, the outcome of the flap, and the healing observed at the donor site are reported. RESULT: The sizes of the flaps were 6-20 × 4-6.5 cm. The time required to harvest the supraclavicular flap ranged from 25 to 35 min and averaged 30 min. The amount of intraoperative blood loss ranged from 20 to 100 ml and averaged 58.8 ml. The duration of postoperative drainage tube placement ranged from 3 to 8 days and averaged 5.9 days. A total of 23 flaps survived. In two cases, the distal blood supply of the flaps was poor, but the flaps survived after debridement and suturing. One flap had partial necrosis, but survived after conservative treatment. All donor area defects were directly sewed and stitched without complications. CONCLUSION: There are multiple advantages of the supraclavicular flap, including simple preparation technique, reliable repair of the defects, and without the need for performing microvascular anastomosis. It can be safely used in head and neck reconstruction after surgery.

Magnifying endoscopy with narrow-band imaging to assist the linear stapler closure of the pharynx during total laryngectomy.

OBJECTIVE: This study aimed to present a novel technique for stapler-assisted laryngectomy under direct visualization using a videoendoscope with narrow-band imaging (NBI-endoscopy). METHODS: A case series of five consecutive patients were treated with stapler-assisted total laryngectomy from December 2014 to March 2016. The technique involved monitoring the stapler closure of laryngopharyngeal cavity under NBI-endoscopic vision, triple checking of neo-pharynx cavity by an endoscopic view inside and transillumination verification outside, air leakage test, and guiding the insertion of feeding tube under direct visualization. The main evaluation of this study was pharyngocutaneous fistula, surgical margin, and oral feeding time. RESULTS: All the patients healed well without a pharyngocutaneous fistula. The mean of surgical time, oral feeding, and hospitalization time were 40 min, 6 days, and 8 days, respectively. CONCLUSION: This study demonstrated a technique simple to learn and associated with decreased complication rates, which could be safe and efficient for stapler-assisted laryngectomy.

Reconstruction of through-and-through cheek defects with folded free anterolateral thigh flaps.

PURPOSE: The purpose of this study was to assess the clinical application and therapeutic efficacy of through-and-through cheek defects reconstructed with folded anterolateral thigh (ALT) flaps. PATIENTS AND METHODS: From January 2009 to May 2012, 10 patients with through-and-through cheek defects resulting from resection of cheek tumor underwent reconstruction with the folded ALT flap at Sun Yat-Sen University Cancer Center, Guangzhou, China. Surgical procedures in harvesting the ALT flap, as well as the surgical anatomy, are described, and the success rate is reported. RESULTS: All ALT flaps were fasciocutaneous flaps. One patient with a thrombotic event required operative exploration in the perioperative period. All 10 flaps were based on a single perforator for reconstruction of defects. In all 10 cases, the donor site was closed primarily for the ALT flap, leaving only a linear scar that was inconspicuous with normal clothing, and the thigh had no functional deficit. CONCLUSIONS: The free ALT flap has good pliability and can be folded for the reconstruction of both the inner and outer lining of through-and-through cheek defects. This flap presents good functional results at the recipient site with the additional advantages of minimal donor-site morbidity, a very acceptable esthetic result, and a high level of patient satisfaction.

Using a linear stapler for pharyngeal closure in total laryngectomy.

This study aimed to evaluate the value of using a linear stapler device in total laryngectomy using a prospective study. Twenty-one total laryngectomies were performed from August 2010 to April 2012, using TA-60 linear stapler for pharyngeal closure. Data collected included age, sex, staging, surgical margins and postoperative course (including complications and swallowing). Patients comprised twenty men and one woman. The mean age was 64 years. Two patients underwent preoperative radiotherapy. Four patients recurred after radiotherapy. Fifteen patients were untreated. Negative surgical margins were achieved in all patients. One patient developed slight pharyngocutaneous fistula. Patients resumed oral intake at 7 days. The mean hospital stay was 10 days. Using a linear stapler to close laryngopharyngeal cavity in total laryngectomy is simple, reliable and practical, avoids pollution of surgical area, saves operation time and decreases the incidence of pharyngocutaneous fistula. It is worthy of clinical application for selected cases.

Clinicopathologic characteristics of second primary squamous cell carcinoma in patients with nasopharyngeal carcinoma after intensity-modulated radiotherapy.

To compare the clinicopathologic characteristics of second primary squamous cell carcinoma (SPSCC) in patients with nasopharyngeal carcinoma (NPC) after intensity-modulated radiotherapy (IMRT) with that after radiotherapy (RT). From 49,021 patients with NPC who treated by definitive RT, we were able to identify 15 male patients with SPSCC after IMRT, and 23 male patients with SPSCC after RT. We examined the difference between groups. In IMRT group, 50.33% developed SPSCC within 3 years, whereas 56.52% developed SPSCC after more than 10 years in RT group. Receiving IMRT was related positively to an increased risk of SPSCC (HR = 4.25; P < 0.001). There was no significant correlation between receiving IMRT and the survival of SPSCC (P = 0.051). Receiving IMRT was related positively to an increased risk of SPSCC, and the latency was much shorter. A follow-up protocol, especially in the first three years, should be designed for NPC patients with IMRT.

Postoperative hypoparathyroidism after thyroid operation and exploration of permanent hypoparathyroidism evaluation.

Background: To investigate the risk factors for hypoparathyroidism, discuss the prevention of postoperative hypoparathyroidism, and explore permanent postoperative hypoparathyroidism evaluation (PPHE). Methods: A total of 2,903 patients with thyroid nodules were treated between October 2012 and August 2015. Serum calcium and intact parathyroid hormone (iPTH) levels were measured at 1 day, 1 month, and 6 months postoperatively. The incidence and management of hypoparathyroidism were analyzed. The PPHE was established based on the risk factors and clinical practice. Results: A total of 637 (21.94%) patients developed hypoparathyroidism, and 92.15% of them had malignant nodules. The incidence rates of transient and permanent hypoparathyroidism were 11.47% and 10.47%, respectively. The iPTH level was lower in patients with malignant nodules who underwent total thyroidectomy (TT) and central-compartment neck dissection (CND). These factors were independently associated with the recovery rate of parathyroid function. The formula for PPHE is as follows: {iPTH} + {sCa} + {surgical procedure} + {reoperation} + {pathologic type}. A scoring system was developed, and we scored low, middle, and high risk of permanent postoperative hypoparathyroidism as 4-6, 7-9, and 10-13, respectively. The differences in the recovery rates of parathyroid function in several risk groups were statistically significant (p < 0.001). Conclusion: Simultaneous TT and CND is a risk factor for hypoparathyroidism. The reoperation is not associated with hypoparathyroidism. Identification of parathyroid glands in situ and preservation of their vascular pedicles are key factors in managing hypoparathyroidism. PPHE can forecast the risk of permanent postoperative hypoparathyroidism well.

Safety and effectiveness of carbon nanoparticles suspension-guided lymph node dissection during thyroidectomy in patients with thyroid papillary cancer: a prospective, multicenter, randomized, blank-controlled trial.

Objective: This study aimed to evaluate the effectiveness and safety of carbon nanoparticles-guided lymph node dissection during thyroidectomy in patients with papillary thyroid cancer(PTC). Methods: Clinical trials consisted of two subgroups: unilateral lobectomy (UL; n=283) and total thyroidectomy (TT; n=286). From each subgroup, the patients were randomly assigned to two groups: the carbon nanoparticle group and control group. Primary endpoints included parathyroid hormone (PTH) levels, number of lymph nodes (LNs) detected, number of tiny lymph nodes detected, and recognition and retention of the parathyroid glands. Secondary endpoint was recognition and protection of the recurrent laryngeal nerve. Results: A total of 569 patients with PTC were recruited. There were no statistically significant differences in demographics between the carbon nanoparticles and control groups (P > 0.05). In the UL subgroup, there were no significant differences in PTH levels between the two groups at preoperative, intraoperative, and postoperative day one, and postoperative month one (P>0.05). There was no significant difference in the serum Ca2+ levels between the two groups preoperatively and at postoperative month one (P>0.05). The number of lymph nodes dissected in the carbon nanoparticles group was significantly higher than that in the control group (P<0.0001). The detection rate of tiny lymph nodes in the carbon nanoparticles group was higher than that in the control group (P=0.0268). In the TT subgroup, there was no significant difference in PTH levels between the two groups at preoperative, intraoperative, and postoperative day one (P>0.05). However, the mean PTH level in the carbon nanoparticles group was significantly higher than that of the control group at postoperative month one (P=0.0368). There was no significant difference in the serum Ca2+ levels between the two groups preoperatively and at postoperative month one (P>0.05). There were no significant differences between the two groups in the number of dissected LNs (P>0.05) or the detection rate of tiny lymph nodes (P>0.05). No drug-related AE and complications due to the injection of carbon nanoparticles were recorded in this study. There were no significant differences between the two groups in terms of parathyroid preserved in situ and recurrent laryngeal nerve injury in the UL and TT subgroups. Conclusions: Carbon nanoparticles demonstrated efficacy and safety in thyroidectomy. The application of carbon nanoparticles could significantly facilitate the identification and clearance of LNs and the optimum preservation of parathyroid function. Clinical trial registration: https://www.chictr.org.cn/, identifier ChiCTR2300068502.

Cell-free DNA methylation biomarker for the diagnosis of papillary thyroid carcinoma.

BACKGROUND: Cell-free DNA (cfDNA) is being explored as biomarker for non-invasive diagnosis of cancer. We aimed to establish a cfDNA-based DNA methylation marker panel to differentially diagnose papillary thyroid carcinoma (PTC) from benign thyroid nodule (BTN). METHODS: 220 PTC- and 188 BTN patients were enrolled. Methylation markers of PTC were identified from patients' tissue and plasma by reduced representation bisulfite sequencing and methylation haplotype analyses. They were combined with PTC markers from literatures and were tested on additional PTC and BTN samples to verify PTC-detecting ability using targeted methylation sequencing. Top markers were developed into ThyMet and were tested in 113 PTC and 88 BTN cases to train and validate a PTC-plasma classifier. Integration of ThyMet and thyroid ultrasonography was explored to improve accuracy. FINDINGS: From 859 potential PTC plasma-discriminating markers that include 81 markers identified by us, the top 98 most PTC plasma-discriminating markers were selected for ThyMet. A 6-marker ThyMet classifier for PTC plasma was trained. In validation it achieved an Area Under the Curve (AUC) of 0.828, similar to thyroid ultrasonography (0.833) but at higher specificity (0.722 and 0.625 for ThyMet and ultrasonography, respectively). A combinatorial classifier by them, ThyMet-US, improved AUC to 0.923 (sensitivity = 0.957, specificity = 0.708). INTERPRETATION: The ThyMet classifier improved the specificity of differentiating PTC from BTN over ultrasonography. The combinatorial ThyMet-US classifier may be effective in preoperative diagnosis of PTC. FUNDING: This work was supported by the grants from National Natural Science Foundation of China (82072956 and 81772850).

Anlotinib in Locally Advanced or Metastatic Radioiodine-Refractory Differentiated Thyroid Carcinoma: A Randomized, Double-Blind, Multicenter Phase II Trial.

PURPOSE: Alhough antiangiogenic agents are the bedrock of treatment for radioiodine-refractory differentiated thyroid carcinoma (RAIR-DTC), novel antiangiogenic agents with optimized features like greater target-binding affinities and more favorable pharmacokinetics profile are needed. This phase II randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of anlotinib, a multikinase inhibitor, for RAIR-DTC. PATIENTS AND METHODS: Patients (ages between 18 and 70 years) with pathologically confirmed locally advanced or metastatic RAIR-DTC were enrolled and randomly received 12 mg anlotinib once daily or placebo on day 1 to 14 every 3 weeks. Patients on placebo were allowed to receive open-label anlotinib after disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints included overall survival (OS) and safety. RESULTS: Between September 2015 and August 2018, 76 and 37 patients randomly received anlotinib and placebo, respectively. Patients receiving anlotinib had a significantly longer median PFS [40.5 months, 95% confidence interval (CI), 28.3-not estimable (NE) versus placebo 8.4 months, 95% CI, 5.6-13.8; HR = 0.21, 95% CI, 0.12-0.37, P < 0.001], meeting the primary endpoint. OS was still immature, with a trend of benefit with anlotinib (HR = 0.57, 95% CI, 0.29-1.12). All patients in the anlotinib group experienced adverse events (AE); 8 (10.5%) discontinued treatment due to AEs. CONCLUSIONS: Anlotinib demonstrated promising efficacy and favorable tolerance in the treatment of locally advanced or metastatic RAIR-DTC, supporting further research to establish its role in the treatment of this serious disease.

Multicenter Randomized Double-Blind Phase III Trial of Donafenib in Progressive Radioactive Iodine-Refractory Differentiated Thyroid Cancer.

PURPOSE: The phase II/III study of donafenib was initiated when there was no available treatment indicated for Chinese patients with progressive radioactive iodine-refractory differentiated thyroid cancer (RAIR-DTC). Donafenib, an oral tyrosine kinase inhibitor (TKI), showed good efficacy and tolerability in the phase II study. We aimed to further evaluate the antitumor activity and safety of donafenib in Chinese patients with RAIR-DTC. PATIENTS AND METHODS: This multicenter, double-blind, placebo-controlled, phase III study enrolled 191 patients with progressive RAIR-DTC and randomized in a ratio of 2:1 to donafenib (300 mg twice daily, n = 128) or matched placebo (n = 63). An open-label donafenib treatment period was allowed upon disease progression. The primary endpoint was progression-free survival (PFS) assessed by the independent review committee. The second endpoints include objective response rate (ORR), disease control rate (DCR), safety, etc. RESULTS: Donafenib demonstrated prolonged median PFS over placebo [12.9 vs. 6.4 months; hazard ratio (HR), 0.39; 95% confidence interval (CI), 0.25-0.61; P < 0.0001] in Chinese patients with RAIR-DTC. Improved ORR (23.3% vs. 1.7%; P = 0.0002) and DCR (93.3% vs. 79.3%; P = 0.0044) were observed in the donafenib group over placebo. For donafenib, the most common grade ≥ 3 treatment-related adverse events (AE) included hypertension (13.3%) and hand-foot syndrome (12.5%), 42.2% underwent dose reduction or interruption, and 6.3% experienced discontinuation. CONCLUSIONS: Donafenib was well-tolerated and demonstrated clinical benefit in terms of improved PFS, ORR, and DCR in patients with RAIR-DTC. The results suggest that donafenib could be a new treatment option for patients with RAIR-DTC.

A "watch window" technique for monitoring buried free jejunum flaps during circumferential pharyngolaryngectomy reconstruction.

The free jejunum flap approach is the optimal option for circumferential pharyngolaryngectomy reconstruction. In this study, we designed a "watch window" for monitoring buried free jejunum flaps, thereby allowing us to assess graft viability. From 2007 to 2011, 14 patients with hypopharyngeal cancer underwent circumferential pharyngolaryngectomy that was reconstructed using a free jejunum flap at the Sun Yat-sen University Cancer Centre. During the closing of the neck incision, a "watch window" was designed for postoperative monitoring. Two patients experienced thrombosis of the pedicle. One was detected early and successfully rescued by removal of the thrombosis, the other one managed with a second free jejunum flap. The success rate of the buried flaps was 92.9%. No pharyngocutaneous fistulas or strictures occurred. All patients eventually resumed oral feeding and swallowing. The "watch window" technique for monitoring buried free jejunum flaps is simple, reliable and useful for finding vascular problems. Level of evidence Case series.

Planned neck dissection before combined chemoradiation in organ preservation protocol for N2-N3 of supraglottic or hypopharyngeal carcinoma.

OBJECTIVE: To investigate the clinical therapeutic outcomes and neck node control of a pretreatment neck dissection in the chemoradiation protocol of organ preservation for N2-N3 of supraglottic and hypopharyngeal carcinoma. METHODS: Forty-six patients (group A) with untreated N2 or N3 squamous cell carcinoma of the supraglottis or hypopharynx underwent pretreatment neck dissection in a chemoradiation protocol, while 39 patients (group B) did not undergo pretreatment neck dissection in a chemoradiation protocol. Salvage surgeries were used for local or cervical node residual tumor or recurrence after chemoradiotherapy. RESULTS: In group A, the mean time between neck dissection and chemoradiation was 21 days (range 15-29). Only 3 patients (6.5%) experienced wound complications. A 'boost' of radiation of 12 Gy was delivered after 33 neck dissections (64.8%) in patients with extracapsular spread. The Kaplan-Meier 5-year overall survival rate was 42.5%. The 5-year overall survival rate and disease-specific survival rate in group A was 42.5 and 46.4%. The rate of neck node control in group A was better than that in group B (86.3 vs. 65.9%, p = 0.02). CONCLUSIONS: Pretreatment neck dissection in a chemoradiation protocol for supraglottic or hypopharyngeal carcinoma showed low complication rates, no delay for radiation, optimal radiation doses, and a high nodal disease control.

Lymph or Chyle Leak After Neck Dissection in Patients With Thyroid Carcinoma: Results of a Study on 1724 Patients.

BACKGROUND: To discuss the prevention and treatment of lymph or chyle leak following neck dissection in patients with thyroid carcinoma. METHODS: A total of 1724 patients with thyroid carcinoma received neck dissection in the Sun Yat-sen University Cancer Center between November 2009 and October 2014. The incidence and management of leak were analyzed. RESULTS: A total of 92 (5.34%) patients developed leak, 28 (1.62%) developed lymph leak, 59 (3.42%) developed chyle leak, and 5 (.29%) developed chylothorax. Medical management to stop postoperative lymph or chyle leak included pressure dressing, reoperation, fasting, or low-fat diet therapy. CONCLUSIONS: Lymph or chyle leak may occur in thyroid carcinoma patients who underwent neck dissection. Clinicians should alert to leak when there were IV + VI region lymph node metastasis and should become aware of chylothorax after pressure dressing. A careful identification and ligation of lymphatic duct may be an effective way to avoid lymph or chyle leak.

Retraction Notice to: Upregulation of OIP5-AS1 Predicts Poor Prognosis and Contributes to Thyroid Cancer Cell Proliferation and Migration.

[This retracts the article DOI: 10.1016/j.omtn.2019.11.036.].

Integrative metabolomic characterization identifies plasma metabolomic signature in the diagnosis of papillary thyroid cancer.

Discrimination of malignancy from thyroid nodules poses challenges in clinical practice. We aimed to identify the plasma metabolomic biomarkers in discriminating papillary thyroid cancer (PTC) from benign thyroid nodule (BTN). Metabolomics profiling of plasma was performed in two independent cohorts of 651 subjects of PTC (n = 215), BTN (n = 230), and healthy controls (n = 206). In addition, 132 patients with thyroid micronodules (<1 cm) and 44 patients with BTN suspected malignancy by ultrasound were used for biomarker validation. Recursive feature elimination algorithm was used for metabolic biomarkers selecting. Significant differential metabolites were demonstrated in patients with thyroid nodules (PTC and BTN) from healthy controls (P = 0.0001). A metabolic biomarker panel (17 differential metabolites) was identified to discriminate PTC from BTN with an AUC of 97.03% (95% CI: 95.28-98.79%), 91.89% sensitivity, and 92.63% specificity in discovery cohort. The panel had an AUC of 92.72% (95% CI: 87.46-97.99%), 86.57% sensitivity, and 92.50% specificity in validation cohort. The metabolic biomarker signature could correctly identify 84.09% patients whose nodules were suspected malignant by ultrasonography but finally histological benign. Moreover, high accuracy of 87.88% for diagnosis of papillary thyroid microcarcinoma was displayed by this panel and showed significant improvement in accuracy, AUC and specificity when compared with ultrasound. We identified a novel metabolic biomarker signature to discriminate PTC from BTN. The clinical use of this biomarker panel would have improved diagnosis stratification of thyroid microcarcinoma in comparison to ultrasound.

Anlotinib in patients with medullary thyroid carcinoma with negative prognostic factors: A sub-analysis based on the ALTER01031 study.

Background: Medullary thyroid carcinoma (MTC) is a rare type of thyroid cancer; however, it accounted for 13.4% of the disease-specific mortalities. ALTER01031 (NCT02586350) was a randomised, placebo-controlled phase 2b trial that evaluated the efficacy and safety of anlotinib in locally advanced or metastatic MTC. This post hoc analysis aimed to evaluate the efficacy and safety of anlotinib in older patients and those with bone metastases using ALTER01031. Methods: In ALTER01031, anlotinib significantly prolonged the median progression-free survival (PFS) from 11.1 months to 20.7 months compared with placebo in the whole population. Patients who were older (≥ 50 years) or had bone metastases were selected. PFS and overall survival (OS) were estimated and compared between patients receiving anlotinib or placebo in each subgroup. A sub-analysis of tumour response and safety was also performed. Results: Patients with older age or bone metastases experienced rapid disease progression as the median PFS was 6.8 months and 7.0 months respectively in the placebo group. Anlotinib significantly improved the median PFS to 17.5 months (P = 0.002) and 20.7 months (P = 0.029) with hazard ratio (HR) of 0.31 (95% CI, 0.15-0.68) and 0.44 (95% CI, 0.20-0.94) compared with placebo. Significant benefit in OS was observed in patients with older age after a longer follow-up (HR = 0.47 [95% CI, 0.22-0.99], P = 0.041). The safety profile of these subgroups was similar to that of the entire population. Conclusion: This sub-analysis demonstrated significant survival benefits and favourable safety of anlotinib in patients with MTC who had old age or bone metastases, supporting the feasibility of anlotinib in these patients.

Distinct molecular subtypes of papillary thyroid carcinoma and gene signature with diagnostic capability.

Papillary thyroid carcinoma (PTC) is heterogeneous and its molecular characteristics remain elusive. We integrated transcriptomic sequencing, genomic analysis and clinicopathologic information from 582 tissue samples of 216 PTC and 75 benign thyroid nodule (BTN) patients. We discovered four subtypes of PTC including Immune-enriched Subtype, BRAF-enriched Subtype, Stromal Subtype and CNV-enriched Subtype. Molecular subtypes were validated in an external cohort of 497 PTC cases from the TCGA. Tumors in the Immune-enriched Subtype showed higher immune infiltration and overexpression of immune checkpoints, whilst BRAF-enriched Subtype showed a higher tendency for extrathyroidal extension and more advanced TNM stage. Key oncogenes including LRRK2, SLC34A2, MUC1, FOXQ1 and KRT19 were overexpressed and enriched in oncogenic MAPK and PI3K/AKT signaling pathways in BRAF-enriched subtype. Further analysis of BRAF-enriched Subtype identified three subclasses with different degrees of malignancies. We also uncovered the molecular link of the initiation and progression from BTN to subtypes of PTC using trajectory analysis. Moreover, a 20-gene expression signature was generated for differential diagnosis of PTC from BTN patients. Together, our work identified previously unreported molecular subtypes of PTC, offering opportunities to stratify patients into optimal treatment plans based on molecular subtyping.

Reconstruction of soft-tissue defects of the head and neck: radial forearm flap or anterolateral thigh flap?

This study compared the reliability, practicability and impact to donor site functionality of radial forearm (RF) and anterolateral thigh (ALT) flaps used for the reconstruction of head and neck soft-tissue defects. The clinical data of patients who underwent reconstruction using RF flaps (n = 53) and ALT flaps (n = 21) after tumour ablation were reviewed. Pedicle length, skin area harvested and flap survival rate were compared between the two flap types. A questionnaire was used to compare the patients' perceptions of donor site functionality. Pedicle length did not significantly differ between RF and ALT flaps (7.5 vs. 9 cm, p = 0.733). A significantly larger mean area of skin was harvested in the ALT group than in the RF group (65 vs. 38 cm(2), p = 0.001). Flap survival rates did not differ between the two groups (p = 0.554). Patients in the ALT group were more satisfied with the appearance of the donor sites than were those in the RF group (p = 0.029). Significantly more patients in the RF group complained of donor site numbness than in the ALT group (p = 0.014). No ALT group patients complained of movement impairment or weakness at the donor sites, but 10% of RF group patients experienced impairment (p = 0.014) and 35% felt weakness (p = 0.001). The ALT and RF flaps showed similar practicability and reliability for the reconstruction of soft-tissue defects, but ALT flaps had fewer impacts to donor site functionality than RF flaps.

A Randomized, Phase III Study of Lenvatinib in Chinese Patients with Radioiodine-Refractory Differentiated Thyroid Cancer.

PURPOSE: Lenvatinib has shown efficacy in treating radioiodine-refractory differentiated thyroid cancer (RR-DTC) in the multinational phase III SELECT study; however, it has not been tested in Chinese patients with RR-DTC. PATIENTS AND METHODS: Chinese patients with confirmed RR-DTC (n = 151) were randomly assigned 2:1 to receive lenvatinib 24 mg/day or placebo in 28-day cycles. The primary endpoint was progression-free survival, and key secondary endpoints included objective response rate and safety. Analyses for progression-free survival and objective response rate were conducted using Response Evaluation Criteria in Solid Tumors v1.1 and confirmed by independent imaging review. All adverse events were assessed and monitored. RESULTS: Progression-free survival was significantly longer with lenvatinib treatment [n = 103; median 23.9 months; 95% confidence interval (CI), 12.9-not estimable] versus placebo (n = 48; median 3.7 months; 95% CI, 1.9-5.6; hazard ratio = 0.16; 95% CI, 0.10-0.26; P < 0.0001). The objective response rate was 69.9% (95% CI, 61.0-78.8) in the lenvatinib arm and 0% (95% CI, 0-0) in the placebo arm. At data cutoff, 60.2% of patients receiving lenvatinib remained on treatment; treatment-emergent adverse events led to lenvatinib discontinuation in 8.7% of patients. Overall, treatment-emergent adverse events of grade ≥3 occurred in 87.4% of patients in the lenvatinib arm, the most common being hypertension (62.1%) and proteinuria (23.3%). CONCLUSIONS: Lenvatinib at a starting dose of 24 mg/day significantly improved progression-free survival and objective response rate in Chinese patients with RR-DTC versus placebo. There were no new or unexpected toxicities. Results are consistent with those from SELECT involving patients with RR-DTC.

Anlotinib in Locally Advanced or Metastatic Medullary Thyroid Carcinoma: A Randomized, Double-Blind Phase IIB Trial.

PURPOSE: Medullary thyroid cancer (MTC) accounts for about 2% of all thyroid cancer, but has a relatively poor prognosis compared with differentiated thyroid cancer. Anlotinib is a novel multitarget tyrosine kinase inhibitor targeting VEGFR, PDGFR, FGFR, and c-Kit. This multicenter, randomized, double-blind, placebo-controlled phase IIB study (ALTER 01031 and NCT02586350) was conducted to investigate the efficacy and safety of anlotinib in MTC. PATIENTS AND METHODS: Patients with histopathologically confirmed, unresectable locally advanced or metastatic MTC were enrolled and randomly assigned in a 2:1 ratio to receive anlotinib (12 mg once daily from day 1 to 14 every 3 weeks) or placebo. Patients in placebo group were allowed to receive open-label anlotinib after disease progression. The primary endpoint was progression-free survival (PFS); secondary endpoints included objective response rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS: Ninety-one patients were enrolled. At data cutoff date, the median PFS was significantly prolonged in the anlotinib group than in the placebo group (20.7 months vs. 11.1 months, P = 0.029; HR, 0.53; 95% confidence interval, 0.30-0.95). The ORR of anlotinib treatment was 48.4%. The incidence of treatment-related adverse events (TRAE) was 100% and 89.7% in the anlotinib and placebo groups, respectively. The most common TRAEs of all grades in the anlotinib group were palmar-plantar erythrodysesthesia syndrome (62.9%), proteinuria (61.3%), and hypertriglyceridemia (48.4%). CONCLUSIONS: Anlotinib demonstrates its efficacy and safety in this phase IIB trial for the treatment of MTC and may become a new choice for this rare disease, especially for Chinese patients.