Potential Impact of Body Mass Index on the Clinical Outcome of Papillary Thyroid Cancer After High-Dose Radioactive Iodine Therapy.

Context: Obesity has been reported as a potential risk factor for the aggressiveness of papillary thyroid cancer (PTC), but the data gathered so far are conflicting. Objective: The aim of our study was to evaluate the relationship between body mass index (BMI) and aggressiveness of PTC at the diagnosis and clinical outcome. Methods: A total of 337 patients who underwent radioactive iodine (RAI) therapy between March 2017 and May 2020 were recruited. Patients were divided into four groups: underweight (BMI<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obese (BMI≥ 30 kg/m2). Treatment and follow-up were defined according to criteria used in the 2015 ATA guidelines. Results: This study included 337 patients with PTC (71.5% women, median age 45.21 ± 13.04 years). The mean BMI was 24.2 ± 3.1 kg/m2. Obese groups had a higher age than the other groups (P = 0.001). Moreover, obese patients had larger tumor sizes and higher T stage, compared to overweight, normal weight, and underweight patients (P = 0.007). After a median follow-up of 32 months, 279 patients (82.7%) had achieved an excellent response (ER) to therapy. The overall ER rates were compared between groups, and they did not differ significantly. Conclusions: We demonstrated that BMI may have an additive effect on the aggressiveness of PTC, but did not have an effect on the response to therapy after high-dose RAI therapy.

The genetic duet of BRAF V600E and TERT promoter mutations predicts the poor curative effect of radioiodine therapy in papillary thyroid cancer.

OBJECTIVE: The BRAF V600E and TERT promoter mutations are well known to be associated with poor clinical outcomes of papillary thyroid cancer (PTC). Radioactive iodide (RAI)-refractory can be evaluated in advance of treatment, for which predictive biomarkers may be helpful. The present study is to analyze the correlation of both mutations with the curative effect of radioiodine therapy. METHODS: A total of 126 patients who underwent RAI therapy from October 2016 to August 2019 were recruited. Treatment and follow-up were defined according to criteria used in the 2015 ATA guidelines. The RAI response of patients was assessed as excellent response (ER) and RAI-refractory at the end of follow-up. RESULTS: When dividing the 126 patients into 4 groups, the no mutation, only BRAF V600E mutation, only TERT promoter mutation, and coexistence of two mutation groups were found in 15.8%, 68.3%, 2.4%, and 13.5% patients. RAI-refractory was found in 52.9% (9/17) patients with the coexisting BRAF and TERT mutations. In logistic regression analysis, M1, BRAF, and TERT mutation were confirmed to be independent factors predicting the RAI-refractory. Moreover, 35.3%, 41.2%, and 23.5% of patients in the BRAF and TERT mutation group were assessed as ER, SIR, and BIR respectively. Kaplan-Meier analyses revealed that the genetic duet of BRAF V600E and TERT promoter mutations was associated with a lower ER reached time. CONCLUSIONS: We found that BRAF V600E and TERT promoter mutation is significantly correlated with the poor curative effect of RAI therapy in PTC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: ChiCTR1800018760.

The radiomics-based tumor heterogeneity adds incremental value to the existing prognostic models for predicting outcome in localized clear cell renal cell carcinoma: a multicenter study.

PURPOSE: Tumor heterogeneity, which is associated with poor outcomes, has not been exhibited in the University of California, Los Angeles, Integrated Staging System (UISS), and the Stage, Size, Grade and Necrosis (SSIGN) scores. Radiomics allows an in-depth characterization of heterogeneity across the tumor, but its incremental value to the existing prognostic models for clear cell renal cell carcinoma (ccRCC) outcome is unknown. The purpose of this study was to evaluate the association between the radiomics-based tumor heterogeneity and postoperative risk of recurrence in localized ccRCC, and to assess its incremental value to UISS and SSIGN. METHODS: A multicenter 866 ccRCC patients derived from 12 Chinese hospitals were studied. The endpoint was recurrence-free survival (RFS). A CT-based radiomics signature (RS) was developed and assessed in the whole cohort and in the subgroups stratified by UISS and SSIGN. Two combined nomograms, the R-UISS (combining RS and UISS) and R-SSIGN (combining RS and SSIGN), were developed. The incremental value of RS to UISS and SSIGN in RFS prediction was evaluated. R statistical software was used for statistics. RESULTS: Patients with low radiomics scores were 4.44 times more likely to experience recurrence than those with high radiomics scores (P<0.001). Stratified analysis suggested the association is significant among low- and intermediate-risk patients identified by UISS and SSIGN. The R-UISS and R-SSIGN showed better predictive capability than UISS and SSIGN did with higher C-indices (R-UISS vs. UISS, 0.74 vs. 0.64; R-SSIGN vs. SSIGN, 0.78 vs. 0.76) and higher clinical net benefit. CONCLUSIONS: The radiomics-based tumor heterogeneity can predict outcome and add incremental value to the existing prognostic models in localized ccRCC patients. Incorporating radiomics-based tumor heterogeneity in ccRCC prognostic models may provide the opportunity to better surveillance and adjuvant clinical trial design.

Could Urinary Iodine Be an Effective Predictive Factor for Thyroid Cancer After High Dose Radioactive Iodine Therapy?

OBJECTIVE: The study aimed to investigate whether urinary iodine concentration (UIC) and urinary iodine to creatinine ratio (UICR) measurements can act as markers for the curative effect of radioactive iodine (RAI) therapy. METHODS: A total of 337 patients who underwent RAI therapy between May 2018 and March 2020 were recruited. According to the levels of UIC or UICR, patients were divided into 6 groups: group A, UIC levels of <100 µg/L; group B, UIC levels ranging from 100 to 200 µg/L; group C, UIC levels of ≥200 µg/L; group D, UICR levels of <100 µg/g; group E, UICR levels ranging from 100 to 200 µg/g; and group F, UICR levels of ≥200 µg/g. Treatment and follow-up were defined according to the criteria used in the 2015 ATA guidelines. RESULTS: When dividing the 337 patients into 3 groups according to UIC levels, 50.7%, 22.6%, and 26.7% of patients were in the A, B, and C groups, respectively. Based on the UICR levels, 58.1%, 29.4%, and 12.5% of patients were in the D, E, and F groups, respectively. There was a significant positive correlation between UIC and UICR levels and iodine-131 uptake rates (P < .001). The excellent response rate was not significantly different between the UIC groups (P = .997) and the UICR groups (P = .634). In logistic regression analysis, UIC and UICR levels were not confirmed to be independent factors predicting the excellent response status, but an age of ≥55 years (OR = 0.373; P = .007) and Tg levels of ≥10 ng/mL (OR = 18.972; P = .001) were confirmed to be independent factors predicting the excellent response status at the end of follow-up. CONCLUSION: The UIC or UICR levels before RAI therapy did not compromise the therapeutic response to iodine-131.

Delay of initial radioactive iodine therapy beyond 3 months has no effect on clinical responses and overall survival in patients with thyroid carcinoma: A cohort study and a meta-analysis.

BACKGROUND: More than a third of thyroid carcinoma (TC) patients require treatment with radioactive iodine (RAI), but the timing of initial RAI therapy after thyroidectomy remains controversial. METHODS: We included 1224 differentiated thyroid carcinoma (DTC) patients during 2015-2019, divided them into the early (≤3 months) and the delayed (>3 months) groups based on the interval between surgery and the initial RAI. Clinical outcomes were assessed within 6-8 months of treatment with RAI, including excellent response (ER), indeterminate response (IDR), biochemical incomplete (BIR) and structural incomplete response (SIR). Further transformed them into dichotomous outcomes, we therefore introduced the ordered/binary logistic regression to assess the relation of time interval and quaternary/dichotomous outcomes, respectively. Finally, we conducted a meta-analysis for cohort study to investigate the effect of timing of RAI therapy on the prognosis of TC. RESULTS: Delay RAI therapy beyond 3 months reduced the IR (BIR + SIR) rate in the present cohort study (RR = 0.67, 95% CI: 0.49-91). Following meta-analysis including 38,688 DTC patients confirmed these results (RR = 0.77, 95% CI: 0.66-0.91), further revealed the duration of treatment does not influence OS (pooled RR = 1.05, 95% CI: 0.83-1.33). CONCLUSION: Delayed initial RAI therapy beyond 3 months but no later than 6 months did not impair the prognosis of TC.

Comparison of PET/CT and MRI in the Diagnosis of Bone Metastasis in Prostate Cancer Patients: A Network Analysis of Diagnostic Studies.

BACKGROUND: Accurate diagnosis of bone metastasis status of prostate cancer (PCa) is becoming increasingly more important in guiding local and systemic treatment. Positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) have increasingly been utilized globally to assess the bone metastases in PCa. Our meta-analysis was a high-volume series in which the utility of PET/CT with different radioligands was compared to MRI with different parameters in this setting. MATERIALS AND METHODS: Three databases, including Medline, Embase, and Cochrane Library, were searched to retrieve original trials from their inception to August 31, 2019 according to the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) statement. The methodological quality of the included studies was assessed by two independent investigators utilizing Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). A Bayesian network meta-analysis was performed using an arm-based model. Absolute sensitivity and specificity, relative sensitivity and specificity, diagnostic odds ratio (DOR), and superiority index, and their associated 95% confidence intervals (CI) were used to assess the diagnostic value. RESULTS: Forty-five studies with 2,843 patients and 4,263 lesions were identified. Network meta-analysis reveals that 68Ga-labeled prostate membrane antigen (68Ga-PSMA) PET/CT has the highest superiority index (7.30) with the sensitivity of 0.91 and specificity of 0.99, followed by 18F-NaF, 11C-choline, 18F-choline, 18F-fludeoxyglucose (FDG), and 18F-fluciclovine PET/CT. The use of high magnetic field strength, multisequence, diffusion-weighted imaging (DWI), and more imaging planes will increase the diagnostic value of MRI for the detection of bone metastasis in prostate cancer patients. Where available, 3.0-T high-quality MRI approaches 68Ga-PSMA PET/CT was performed in the detection of bone metastasis on patient-based level (sensitivity, 0.94 vs. 0.91; specificity, 0.94 vs. 0.96; superiority index, 4.43 vs. 4.56). CONCLUSIONS: 68Ga-PSMA PET/CT is recommended for the diagnosis of bone metastasis in prostate cancer patients. Where available, 3.0-T high-quality MRI approaches 68Ga-PSMA PET/CT should be performed in the detection of bone metastasis.

Lymph node metastases >5 and metastatic lymph node ratio >0.30 of differentiated thyroid cancer predict response to radioactive iodine.

PURPOSE: The study was designed to elucidate the predictive value of the number of lymph node metastases (LNMs) and lymph node ratio (LNR) for response to therapy restratification system (RTRS). METHODS: From December 2015 to December 2019, 1228 patients who accepted radioactive iodine (RAI) were collected in the study. After 6-8 months, response to RAI was evaluated as complete response (excellent response) and incomplete response (indeterminate, biochemical, and structural incomplete response). The study developed classification tree to determine the optimum LNMs and LNR that predicted response to RAI. Multivariate logistic regression analyses were further analyzed to find independent factors of response to RAI. RESULT: The mean age of patients was 44 ± 12 and 71.09% (873/1228) were females. The best cutoff value of LNMs to affect RAI treatment response determined by classification tree was 5. Further in 388 patients with LNMs >5, the best cutoff value of LNR to affect RAI treatment response determined by classification tree was 0.30. With multivariate analysis, the study found that LNMs (>5), gender, lymph node dissection, and American Thyroid Association (ATA) risk classification were independent predictors of response to RAI for all 1228 patients; and LNR (>0.30), gender, and ATA risk classification for 388 patients with LNMs >5. The sensitivity analysis indicated that whether patients with LNM or not were included, the multivariate logistic regression model was kept stable. On subgroup analysis, no significant interactions were observed between the effect of LNMs/LNR and gender, N stage, ATA risk classification, lymph node dissection, or T stage. CONCLUSIONS: With classification tree, the study found that LNMs and LNR could predict initial response to RAI, and their optimal cutoff values were 5 and 0.30, separately.

Preablative Stimulated Thyroglobulin and Thyroglobulin Reduction Index as Decision-Making Markers for Second Radioactive Iodine Therapy in Patients with Structural Incomplete Response.

PURPOSE: The aim of this study was to evaluate the value of preablative stimulated thyroglobulin (presTg) and thyroglobulin reduction index (TRI) to predict the different responses to second radioactive iodine (RAI) therapy in differentiated thyroid cancer (DTC) patients with structural incomplete response (SIR). PATIENTS AND METHODS: A single-center retrospective study analyzed the different clinical outcomes after second RAI therapy in 206 patients with SIR. PresTg1 and presTg2 were measured before first and second RAI management and TRI was the reduction index of presTg1 and presTg2. Cut-off values of presTg and TRI were obtained using receiver operating characteristic analysis. The univariate logistic regression analysis was performed to confirm these parameters as prognostic factors to predict different responses to second RAI therapy. RESULTS: Only ATA risk stratification, the post-therapy whole-body scanning (Rx-WBS) findings, presTg1, presTg2, TRI, were different in patients with SIR. After second RAI therapy, 28.2% (58/206) of patients with SIR initially were reclassified as excellent response (ER). PresTg1 <6.6 ng/mL, presTg2 <1.2ng/mL, and TRI >74.2% were excellent indications to predict ER from non-ER after second RAI treatment. PresTg1 >14.9 ng/mL, presTg2 >1.8ng/mL and TRI <66.5% were well markers to predict poor outcome (SIR). High risk and distant metastases could still be considered as risk factors. CONCLUSION: DTC patients with SIR could benefit through second RAI treatment. PresTg before each RAI therapy and TRI could be considered as effective decision-making markers for second RAI therapy and as predictive indications for clinical outcomes.

Clinical Analysis of the Short-Term Outcome of Papillary Thyroid Micro Carcinoma After 131I Treatment.

PURPOSE: To explore the factors that influence the short-term clinical outcome after the first 131I treatment of papillary thyroid micro carcinoma (PTMC). PATIENTS AND METHODS: From October 2015 to June 2018, patients who were diagnosed with PTMC with lymph node metastasis were analyzed retrospectively, excluding patients with incomplete clinical data, distant metastasis, positive TGAb, TSH<30 mIU/L. The baseline data of sex, age, time from last surgery to first 131I treatment, tumor pathology information, and biochemical information were collected before admission. All patients included had radioactive iodine (RAI) with 3.70 GBq. The treatment response of patients was evaluated 6-8 months after discharge. By means of univariate and multivariate analysis, including excellent response (ER) and non-excellent response (NER) groups of clinical data, we assessed the impact of 131I on patients' outcome. A nomogram model was established based on the above independent risk factors. RESULTS: A total of 206 patients (59 males and 147 females, mean age 43.4 ± 10.6 years) were included in the study. The median follow-up time was 169.4 ± 10.5 days, including 139 patients in ER group (67.4%) and 67 patients in NER group (32.5%). Four factors including combining Hashimoto's thyroiditis, pre-ablative Tg levels, UIE levels, and lateral lymph node numbers were statistically different between ER group and NER group with significance at P < 0.05. Further multivariate analysis showed that Hashimoto's thyroiditis and Ps-Tg levels could be used as independent factors. The model verification showed that the C-index of the modeling set was 0.822, indicating that the nomogram model had a good predicted accuracy. CONCLUSION: Our data suggest that coexisting Hashimoto's thyroiditis and elevated Ps-Tg levels are predictive factors for short-term outcome of thyroid micro papillary carcinoma after 131I treatment. Also, the nomogram model had a good predicted accuracy.

Analysis of Curative Effect and Influencing Factors of N1 Stage Papillary Thyroid Micro-Carcinoma and Papillary Thyroid Non-Micro Carcinoma After Initial Radioactive Iodine Ablation Therapy.

OBJECTIVE: To compare the efficacy and influencing factors of initial radioactive iodine (RAI) ablation therapy for postoperative N1 stage papillary thyroid micro-carcinoma (PTMC) and papillary thyroid non-micro carcinoma (PTC), and to explore the necessity of RAI for N1 stage PTMC. METHODS: A retrospective analysis of patients with N1 stage papillary thyroid cancer who underwent RAI in our department from January 2018 to June 2019. According to the tumor diameter, papillary thyroid carcinoma was divided into PTMC group (≤ 1.0cm) with 129 patients and PTC group (> 1.0 cm) with 214 patients. According to the 2015 ATA guidelines, the patient's treatment response was evaluated 6-8 months after discharge from the hospital: excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), and structural incomplete response (SIR). IDR, BIR, and SIR were classified into NER group. Chi-squared test, independent sample t-test, Mann-Whitney U test, and binary logistic regression analysis were used to compare the differences between PTMC and PTC patients. RESULTS: The ps-Tg of the PTMC group was significantly lower than that of the PTC group (P = 0.001), and the ER ratio of the PTMC group was higher (χ2 = 5.445, P < 0.05). The ER ratio of PTMC patients in the N1a group was significantly higher than that of PTC patients (80%, 66.7%, χ2 = 4.076, P < 0.05), while the ER ratio of PTMC in the N1b group was not significantly different from that of PTC. Gender, N stage, and ps-Tg were found to be independent factors of RAI treatment response. CONCLUSION: The efficacy of the initial RAI of PTMC patients was significantly better than that of PTC patients. There was no significant difference in the efficacy of RAI between males with PTMC, N1b stage, ps-Tg ≥ 5.87ng/mL and PTC patients, which suggested that RAI is necessary for these patients.

A pre-ablative thyroid-stimulating hormone with 30-70 mIU/L achieves better response to initial radioiodine remnant ablation in differentiated thyroid carcinoma patients.

Our aim was to clarify the optimum pre-ablative thyroid-stimulating hormone (TSH) level for initial radioiodine remnant ablation (RRA) in patients with differentiated thyroid carcinoma (DTC). From December 2015 to May 2019, 689 patients undergone RRA at Nuclear Medicine Department, Second Hospital of Shandong University were included in the study. Patients were categorized by their pre-ablative TSH level grouping of < 30, 30-70 and ≥ 70 mIU/L. Response to RRA were evaluated as complete response (including excellent and indeterminate response) and incomplete response (including biochemical and structural incomplete response) after a follow-up of 6-8 months. Multivariable binary logistic regression model was used to explore the optimum pre-ablative TSH level range and independent factors associated with response to RRA. Rates of complete response to RRA were 63.04%, 74.59% and 66.41% in TSH level groups of < 30, 30-70 and ≥ 70 mIU/L, separately. With multivariate analysis, the study found that pre-ablative TSH levels, gender and lymph node dissection were independent predictors of response to RRA. TSH between 30 and 70 mIU/L had a higher rate of complete response compared with TSH < 30 mIU/L, OR 0.451 (95% CI 0.215-0.958, P = 0.036). A pre-ablative TSH level of 30-70 mIU/L was appropriate for patients with DTC to achieve a better response to RRA.

Analysis of the incidence and influencing factors of hyponatremia before 131I treatment of differentiated thyroid carcinoma.

BACKGROUND: Hyponatremia is a common clinical electrolyte disorder. However, the association between hyponatremia and acute hypothyroidism is unclear. Acute hypothyroidism is usually seen in patients who undergo preparation for radioactive iodine therapy. AIM: To analyze the incidence and influencing factors of hyponatremia in a condition of iatrogenic acute hypothyroidism in patients with differentiated thyroid cancer (DTC) before 131I treatment. METHODS: The study group consisted of 903 DTC patients who received 131I treatment. The clinical data before and after surgery, as well as on the day of 131I treatment were analyzed. According to the blood sodium level before 131I treatment, patients were divided into the non-hyponatremia group and hyponatremia group. Correlations between serum sodium levels before 131I treatment and baseline data were analyzed. Univariate analysis and binary logistic regression were performed to identify the influencing factors of hyponatremia. RESULTS: A total of 903 patients with DTC, including 283 (31.3%) males and 620 (68.7%) females, with an average age of 43.8 ± 12.7 years, were included in this study. The serum sodium levels before surgery and 131I treatment were 141.3 ± 2.3 and 140.5 ± 2.1 mmol/L, respectively (P = 0.001). However, the serum sodium levels in males and females before 131I treatment were lower than those before surgery. Patients aged more than 60 years and less than 60 years also showed decreased serum sodium levels before 131I treatment. In addition, the estimated glomerular filtration rate (eGFR) in males and females decreased before 131I treatment compared with those before surgery (P = 0.001). Moreover, eGFR in patients over 60 years and under 60 years decreased before 131I treatment, when compared with that before surgery. There were no significant differences in serum potassium, calcium, albumin, hemoglobin, and blood glucose in patients before surgery and 131I treatment (P > 0.05). Among the 903 patients, 23 (2.5%) were diagnosed with hyponatremia before 131I treatment, including 21 cases (91.3%) of mild hyponatremia and 2 cases (8.7%) of moderate hyponatremia. Clinical data showed that patients with mild hyponatremia had no specific clinical manifestations, while moderate hyponatremia cases were mainly characterized by fatigue and dizziness, which were similar to neurological symptoms caused by hypothyroidism and were difficult to distinguish. Correlation analysis showed a correlation between serum sodium before 131I treatment and the preoperative level (r = 0.395, P = 0.001). There was no significant correlation between blood sodium and thyroid-stimulating hormone (TSH) levels and urine iodine before 131I treatment (r = 0.045, P = 0.174; r = 0.013, P = 0.697). Univariate analysis showed that there were significant differences in age, sex, history of diuretic use, distant metastasis, preoperative blood sodium, blood urea nitrogen (BUN), eGFR, TSH and urinary iodine between the two groups (all P < 0.05). Logistic regression analysis showed that factors such as history of diuretic use, distant metastases, preoperative sodium and BUN were all influencing factors of hyponatremia. The Hosmer and Lemeshow test (c2 = 2.841, P = 0.944) suggested a high fit of the model. Omnibus tests of model coefficients indicated the overall significance of the model in this fitted model (P < 0.05). Preoperative serum sodium was a significant factor associated with pre-131I therapy hyponatremia (OR = 0.763; 95%CI: 0.627-0.928; P = 0.007). CONCLUSION: The incidence of hyponatremia induced by 131I treatment preparation was not high. Preparation for radioactive iodine therapy was not a risk factor for the development of hyponatremia in thyroid cancer patients.

Comparative diagnostic accuracy of respective nuclear imaging for suspected fracture-related infection: a systematic review and Bayesian network meta-analysis.

BACKGROUND: The aim of this study was to compare the accuracy of available nuclear imaging modalities in the diagnosis of suspected fracture-related infection (FRI). METHODS: We conducted a comprehensive literature search of PubMed, EMBASE and the Cochrane Library to retrieve diagnostic accuracy studies in which FRI was investigated using different nuclear imaging modalities. The pooled sensitivity, specificity, likelihood ratios and diagnostic odds ratios were constructed using the bivariate meta-analysis framework, while the superior index was pooled using Bayesian network meta-analysis. RESULTS: 22 eligible studies (1,565 patients) were included in the quantitative analysis. A broad overlapping confidence interval (CI) of pooled sensitivity was observed among bone scintigraphy (0.94; 95% CI 0.85-0.98), 18F-FDG PET and PET/CT (0.91; 95% CI 0.85-0.94) and leukocyte scintigraphy (0.86; 95% CI 0.53-0.97). Bone scintigraphy (0.34; 95% CI 0.08-0.75) seemed to be less specific than all the other modalities, while leukocyte scintigraphy (0.96, 95% CI 0.92-0.98) was notably more specific than 18F-FDG PET and PET/CT (0.78; 95% CI 0.69-0.85). Based on the superiority index, 18F-FDG PET/CT (3.78; 95% CI 0.14-11.00), 18F-FDG PET (2.98; 95% CI 0.14-9.00) and leukocyte scintigraphy (1.51; 95% CI 0.11-7.00) all achieved high accuracy in detecting FRI. CONCLUSION: Bone scintigraphy is a highly sensitive nuclear imaging technique but lacks the specificity needed to unequivocally differentiate among various conditions suspected to be FRI. Leukocyte scintigraphy, 18F-FDG PET/CT and PET all present good satisfactory accuracy for the diagnosis of FRI, but their costs should be further reduced to promote their wide application.

[Effects of endostatin on the growth and lymphangiogenesis of Lewis lung carcinoma xenograft in mice].

OBJECTIVE: to investigate the effects of endostar, a recombined humanized endostatin, on the growth, lymphangiogenesis and lymphatic metastasis of Lewis lung carcinoma xenograft in mice. METHODS: lewis lung carcinoma (LLC) xenograft were established in C57 mice by intravenous transplantation of 1 × 10(6) cells. Then tumor-bearing mice were assigned into two groups: control group received caudal vein injections of 0.2 ml of 0.9% sodium chloride for 15 days, and treatment group received 500 µg endostar daily. Six weeks after LLC cell injection mice were sacrificed, and then tumor numbers and size were recorded. The expression of vascular endothelial growth factor-c (VEGF-C) and microlymphatic vessel density (MLVD) were observed by immunohistochemical staining. RESULTS: tumor number and size of control group were significantly higher than those of treatment group. The microlymphatic vessel density (MLVD) was 5.7 ± 1.6 in the treatment group, which was markedly lower than in the control mice (7.8 ± 1.6). Two lymph node metastases were observed in treatment group, and eight in control group. Lymphatic metastases were more frequent in control group than in treatment group. Expression of VEGF-C in control group was significantly higher than that in treatment group. CONCLUSION: endostar significantly inhibits the growth, lymphangiogenesis and lymphatic metastasis of Lewis lung carcinoma xenografts, and the inhibitory effect is due to its ability to regulate the expression of VEGF-C of tumors in part.