Early Structural, Biochemical, and Metabolic Responses to Anlotinib in Patients With Progressive Radioactive Iodine Refractory Differentiated Thyroid Cancer.

OBJECTIVE: We aimed to assess the early efficacy of anlotinib in patients with progressive radioactive iodine refractory differentiated thyroid cancer at the structural, biochemical, and metabolic levels. METHODS: Ten eligible patients were prospectively enrolled to receive anlotinib. Their responses were assessed at 6 weeks. Apart from the structural response according to Response Evaluation Criteria in Solid Tumors version 1.1, the biochemical response was assessed by serum thyroglobulin (Tg), and the metabolic response was assessed by 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) according to the European Organization for Research and Treatment of Cancer criteria. A safety profile was recorded. RESULTS: Structurally controlled disease (20% partial response + 80% stable disease) was observed in all patients. The median longest diameter of target lesions shrank from 20.8 mm (IQR, 14.9-27.5) to 17.0 mm (IQR, 14.1-23.7) (P < .001), and the average shrinkage rate was -15.1 ± 14.1%. Sharp serum Tg reduction by 72.8 ± 16.4% was observed in 8 measurable patients. The 18F-FDG PET/CT-mapped glucose metabolic response was not quite comparable to the structural response, with 90% of the patients having controlled disease (30% partial metabolic response + 60% stable metabolic disease), whereas 10% presented progressive metabolic disease. The most common treatment-emergent adverse events (AEs) were hypertension (100%) and proteinuria (70%). Most AEs were grade 1 or 2, whereas grade 3 AEs occurred only in hypertension. CONCLUSION: Anlotinib is generally well tolerated and can bring early disease control within the initial 6 weeks of treatment. The sharp biochemical response suggests Tg to be an early sensitive biomarker to anlotinib, whereas the heterogeneous metabolic response might play a complementary role.

Radioiodine adjuvant therapy in differentiated thyroid cancer: An update and reconsideration.

Radioiodine (131I) therapy (RAI) has been utilized for treating differentiated thyroid cancer (DTC) for decades, and its uses can be characterized as remnant ablation, adjuvant therapy (RAT) or treatment for known diseases. Compared with the definite 131I treatment targets for remnant ablation and known disease, 131I adjuvant therapy (RAT) aims to reduce the risk of recurrence by destroying potential subclinical disease. Since it is merely given as a risk with no imaging confirmation of persistence/recurrence/metastases, the evidence is uncertain. With limited knowledge and substance, the indication for RAT remains poorly defined for everyday clinical practice, and the benefits of RAT remain controversial. This ambiguity results in a puzzle for clinicians seeking clarity on whether patients should receive RAT, and whether patients are at risk of recurrence/death from undertreatment or adverse events from overtreatment. Herein, we clarified the RAT indications in terms of clinicopathological features, postoperative disease status and response to therapy evaluation, and retrospectively examined the clinical outcomes of RAT as reported in current studies and guidelines. Furthermore, given the evolution of nuclear medicine imaging techniques, it can be expected that the future of RAT may be advanced by nuclear medicine theranostics (i.e., 131I whole-body scan, PET/CT) by accurately revealing the biological behaviors, as well as the underlying molecular background.

Radiologic Response Combined with Dermatologic Toxicities is the Most Robust Predictor of Survival Benefits in Patients with Inoperable Hepatocellular Carcinoma After Transarterial Chemoembolization Plus Sorafenib Therapy.

PURPOSE: The survival benefits of patients with inoperable hepatocellular carcinoma (HCC) who undergo transarterial chemoembolization (TACE) and receive sorafenib therapy remain controversial. We aimed to identify clinical predictors in patients with inoperable HCC undergoing TACE and receiving sorafenib. METHODS: Between January 2014 and December 2017, 148 consecutive patients with inoperable HCC who were treated with TACE plus sorafenib were retrospectively analyzed. Critical clinical factors associated with overall survival (OS) were identified by Cox regression model analysis. Kaplan-Meier methods were used to calculate the survival times, which were compared with the log-rank test. RESULTS: Macrovascular invasion (MVI), radiologic response and sorafenib-related dermatologic toxicities were identified as independent factors associated with OS. MVI is a known prognostic factor before treatment. The median OS of patients with either radiologic response or dermatologic toxicities was significantly improved compared with that of patients without it (both 23.0 vs. 7.0 months, P < 0.001). The median OS of patients with a combination of radiologic response and dermatologic toxicities was significantly longer than that of patients with either radiologic response or dermatologic toxicities, as well as no response (25.0 vs. 14.0 vs. 6.0 months, respectively, P < 0.001), and the predictive value was confirmed across patients with different baseline characteristics in terms of MVI, α-fetoprotein level, performance status and liver function. CONCLUSION: The combination of radiologic response and sorafenib-related dermatologic toxicities is the most robust predictor of survival benefits for HCC patients after TACE plus sorafenib therapy. LEVEL OF EVIDENCE: Level 3.

Apatinib for Patients With Sorafenib-Refractory Advanced Hepatitis B Virus Related Hepatocellular Carcinoma: Results of a Pilot Study.

More than half of the patients with advanced hepatocellular carcinoma (HCC) do not respond to primary treatment with sorafenib. Currently, there are no universally accepted methods for further treatment. This pilot study was performed to assess the safety and effectiveness of apatinib as an optional treatment for patients with sorafenib-refractory HCC. Between January 2015 and May 2017, 43 consecutive patients with sorafenib-refractory advanced HCC who received apatinib were reviewed. The objective response rate (ORR) and disease control rate (DCR) were assessed using modified response evaluation criteria in solid tumors. The time to progression (TTP) and overall survival (OS) were determined using the Kaplan-Meier method. Toxicities associated with apatinib were assessed. All patients had hepatitis B virus (HBV) related HCC. The mean follow-up time was 11 months (range: 3-37) and the mean duration of apatinib was 7.6 months (range: 1-32). After treatment, 11 patients had partial response (PR), 18 had stable disease (SD), and 14 had progressive disease (PD); accordingly, the ORR and DCR were 25.6% and 67.4%, respectively. The median TTP and OS were 3 months (95% confidence interval [CI]: 1.9-4.1) and 8 months (95% CI: 6.9-9.0), respectively. The median OS times for PR, SD, and PD were 19 months (95% CI: 15.8-22.2), 8 months (95% CI: 7.3-8.7), and 4 months (95% CI: 3.1-4.9), respectively (P < .001). The median TTP for PR, SD, and PD was 14 months (95% CI: 11.9-16.1), 3 months (95% CI: 2.3-3.7) and 1 month, respectively (P < .001). No patients experienced toxicity-related death. The most common toxicities were weight loss, hand-foot skin reaction, and hypertension. Twelve adverse events of grade 3 or higher were observed. Based on our findings, apatinib is a promising treatment for patients with sorafenib-refractory advanced HBV-related HCC.

Alpha-fetoprotein assessment for hepatocellular carcinoma after transarterial chemoembolization.

PURPOSE: To evaluate whether AFP classification criteria correlate with tumor response measured using the European Association for the Study of the Liver (EASL) and predicate survival in patients with hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). METHODS: Data from 143 consecutive patients with unresectable HCC and elevated AFP (> 20 ng/mL), who underwent TACE as initial treatment between January 2011 and December 2015 were collected, retrospectively. AFP response was classified as follows: complete response, normalization of AFP; partial response, > 50% decrease from baseline; stable disease, - 50 to + 30% change from baseline; or progressive disease, > 30% increase from baseline. Response rates according to AFP and EASL criteria were compared, and associations between the AFP response and overall survival (OS) were evaluated. RESULTS: The k value for agreement between AFP criteria and EASL criteria was 0.52 (moderate), with response rates of 42.7% and 41.3%, respectively (P = 0.811). The OS of responders was significantly longer compared with non-responders for both AFP (21 vs. 6 months, P < 0.001) and EASL (23 vs. 6 months, P < 0.001). Multivariate analysis revealed that the AFP response (hazard ratio [HR], 0.430, 95% CI, 0.233-0.794; P = 0.007), EASL response (HR, 0.343; 95% CI, 0.176-0.666; P = 0.002), and macroscopic vascular invasion (HR, 2.104; 95% CI, 1.403-3.154; P < 0.001) were significantly associated with OS. CONCLUSIONS: The defined AFP classification criteria was moderate correlated with EASL criteria and predicted the outcome in patients with HCC who underwent TACE.

30mCi radioactive iodine achieving comparative excellent response in intermediate/high-risk nonmetastatic papillary thyroid cancer: a propensity score matching study.

OBJECTIVE: To determine the efficacy of low-dose radioactive iodine (RAI) therapy (30 mCi, 1110 MBq) in Chinese patients with intermediate- to high-risk papillary thyroid cancer (PTC) without distant metastasis. DESIGN AND METHODS: This large retrospective study included Chinese patients with PTC that tested negative for thyroglobulin antibodies. Patients were categorized into low-dose (30 mCi, 1110 MBq) and high-dose (>100 mCi, 3700 MBq) RAI groups. Ablation rate and long-term response were compared between groups using propensity score matching (PSM) to minimize bias and confounding. RESULTS: In total, we included 446 patients. No significant difference in ablation success rate was found between groups (P = 0.305) before or after PSM (N = 162; P = 0.200). Excellent response (ER) rate was not significant between groups before (P = 0.917) or after PSM (P = 0.798). Efficacy of low-dose RAI was similar to that of high-dose RAI in N0- (P = 1.000), N1a- (P = 0.981), and N1b-stage (P = 0.903) patients. Low- and high-dose RAI groups achieved similar ER rates in pre-ablative stimulated thyroglobulin level (≤1 ng/mL, P = 1.000; 1 < ps-Tg ≤ 5 ng/mL, P = 0.444; 5 < ps-Tg ≤ 10 ng/mL, P = 0.665; >10 ng/mL, P = 1.000) and BRAFV600E-positive (P = 0.324) subgroups. CONCLUSIONS: Efficacy of low-dose RAI therapy was similar to that of high-dose for ablation and achieving ER in Chinese nonmetastatic intermediate- to high-risk PTC patients. High-dose RAI could not rectify ablation failure or non-ER rates in PTC patients with BRAFV600E, lymph node metastases, or unfavorable thyroglobulin levels.

Sorafenib continuation or discontinuation in patients with unresectable hepatocellular carcinoma after a complete response.

AIMS: To assess the efficacy of continued administration of sorafenib for patients with unresectable hepatocellular carcinoma (HCC) treated with local regional therapy (LRT) after a complete response (CR), also, the adverse events of sorafenib after discontinuation of administration were observed. METHODS: Between April 2008 and May 2012, 956 consecutive patients with unresectable HCC treated with LRT (transarterial chemoembolization, radiofrequency ablation) combined with sorafenib were retrospectively investigated. Of these, 157 patients with a CR were enrolled: 102 of them continued to receive sorafenib (test group) and the other 55 stopped receiving sorafenib (control group). RESULTS: The median recurrence-free survival (RFS), post-complete response overall survival (pOS) and overall survival (OS) in the test and control groups were 11 months (95% CI: 6.1, 15.9), 25 months (95% CI: 20.7, 29.3) and 33 months (95% CI: 29.2, 36.8) and 12 months (95% CI: 10.4, 13.6), 28 months (95% CI 24.2, 31.8) and 34 months (95% CI: 30.8, 37.2) respectively. The differences in RFS, pOS and OS between the groups were not significant (P = 0.768, 0.797 and 0.730, respectively). The adverse events related to sorafenib resolved after discontinuation of administration and the quality of life (QoL) scores improved. CONCLUSIONS: Patients with unresectable HCC who achieved a CR did not benefit from continued sorafenib in terms of RFS, pOS or OS. The adverse events of sorafenib were reversible, and discontinuation of sorafenib may improve the QoL of patients who have achieved a CR.

Combination of individualized local control and target-specific agent to improve unresectable liver cancer managements: a matched case-control study.

Management of late-stage hepatocellular carcinoma is difficult. A direct comparison of clinical data is needed in order to demonstrate the survival benefits of different therapies. We directly compared various therapies in a retrospective matched case-control study. A total of 79 patients with unresectable tumors greater than 10 cm in size were included in the study between 2008 and 2012. Thirty-five patients were treated with transarterial chemoembolization for local control, 20 were treated with sorafenib systemic chemotherapy, and 24 received combination treatment. The total follow-up time after initial therapy was 4.5 years. Survival time after treatment was significantly longer in the combination therapy group (P < 0.0001). The median survival times for combination, local control, and systemic chemotherapy were 15 (12-21), 10 (9-13), and 3.5 (2.5-9.0) months (95 % confidence interval), respectively. The hazard ratios for local control and systemic chemotherapy were 1.985 and 5.102, respectively, with combination treatment as the reference. There was no observed difference in combination therapy from the side effects of the individual therapies. In conclusion, the limited availability of therapeutic options for late-stage liver cancer necessitates reliance on multidisciplinary personalized medicine approaches with target-specific medications to increase survival time. Combining individualized local control therapy and drugs that target specific disease markers provides more benefits to patients.

Sorafenib continuation after first disease progression could reduce disease flares and provide survival benefits in patients with hepatocellular carcinoma: a pilot retrospective study.

BACKGROUND: Sorafenib is a promising drug for advanced hepatocellular carcinoma (HCC); however, treatment may be discontinued for multiple reasons, such as progressive disease, adverse events, or the cost of treatment. The consequences of sorafenib discontinuation and continuation are uncertain. MATERIALS AND METHODS: We retrospectively analyzed 88 HCC patients treated with sorafenib from July 2007 to January 2013. Overall survival (OS), post-disease progression overall survival (pOS), and time to disease progression (TTP) were compared for survival analysis. Cox proportional hazard regression was performed to assess the effect of important factors on OS in the overall patient population and on pOS in patients who continued sorafenib treatment. RESULTS: Sorafenib was discontinued and continued in 24 and 64 patients, respectively. The median OS (355 vs 517 days respectively; p=0.015) and median post-PD OS (260 vs 317 days, respectively; p=0.020) were statistically different between the discontinuation and continuation groups. Neither the median time to first PD nor the time to second PD were significantly different between the 2 groups. In the discontinuation group, 3 of the 24 patients (12.5%) suffered disease outbreaks. In Cox proportional hazard regression analysis after correction for confounding factors, BCLC stage (p=0.002) and PD site (p=0.024) were significantly correlated with pOS in patients who continued sorafenib treatment. CONCLUSIONS: Sorafenib discontinuation may cause HCC flares or outbreaks. It is advisable to continue sorafenib treatment after first PD, particularly in patients with Barcelona Clinic Liver Cancer stage B disease or only intrahepatic PD.

[The analysis of the efficacy and safety of combined transarterial chemoembolization with sorafenib in patients with large hepatocellular carcinoma].

OBJECTIVE: To evaluate the efficacy and safety of combined transarterial chemoembolization with sorafenib in patients with large hepatocellular carcinoma. METHODS: 79 patients with large HCC(larger than 10 cm in diameter)were enrolled from July 2008 to June 2012 for this retrospective study. 24 patients undertaken TACE combined with sorafenib as T + S group. 35 patients undertaken TACE alone as T group, and other 20 patients treated with sorafenib alone as S group. RESULTS: The median survival time was 15 months in T + S group, 10 months in T group, and 5 months in S group, respectively (P = 0.000). The median time of tumor progress was 6 months, 3 months and 2.5 months, respectively (P = 0.000). The most common adverse events related to sorafenib in group T + S group and S group alone were hand foot skin reaction, diarrhea and alopecia. The incidence rate of adverse events related to sorafenib was no significant difference between two groups. There was no 4 or more grade adverse event occurred in each group. The most common complications related to interventional treatment in group T + S group and T group alone were mild jaundice, ascites, inguinal region hematoma. The incidence rate of complications related to interventional treatment was no significant difference between two groups. CONCLUSION: The combination of TACE and sorafenib in patients with large HCC is well tolerated and safe, which is available to delay tumor progression and prolong survival.

[Research on detection method of adulterated olive oil by Raman spectroscopy and least squares support vector machine].

For the purpose of the authentication of sorts as well as the prediction of contents of the oils which were adulterated into olive oil, 117 olive oil samples adulterated with sunflower seed oil, soybean oil and corn oil were detected by Raman spectroscopy, and least squares support vector machine (LS-SVM) based on multiple iterative optimization was used to identify the type of the adulterant oil, and the composite recognition rate was 97%. In addition, methods such as LS-SVM, ANNs and PLSR were used to build the Raman spectra calibration model of the adulterant oil (sunflower seed oil, soybean oil and corn oil) contents respectively, the results indicated that LS-SVM had the best predictive performance, and the root mean square error of prediction (RMSEP) ranged from 0.007 4 to 0.014 2. Research results showed the method based on Raman spectroscopy and LS-SVM was accurate, fast, simple and non-destructive for adulterated olive oil detection.