Purpose: Alectinib has been approved for anaplastic lymphoma kinase (ALK)–positive non–small cell lung cancer (NSCLC) at 300 mg twice daily in Japan, lower than global standard of 600 mg twice daily. This study evaluated the clinical relevance of the reduced dose by comparing outcomes between the two doses. Materials and Methods: This study included patients with advanced ALK-positive NSCLC who received alectinib at Samsung Medical Center, Korea. The progression-free survival (PFS), overall survival, cumulative incidence of central nervous system (CNS) progression, and safety profiles were retrospectively reviewed and compared. Results: Among 306 patients, 32 and 274 received alectinib at either 300 or 600 mg twice daily, respectively. The 300 mg group showed a slight but not significant advantage in PFS (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.44 to 1.51; p=0.51) and overall survival (HR, 0.51; 95% CI, 0.20 to 1.21; p=0.13). Superior outcome with 300 mg was remarkable in patients with lower body weight (≤ 60 kg), but diminished in patients with higher body weights. Patients with baseline brain metastasis in the 300 mg group exhibited a slight increase in incidence of CNS failure (HR, 1.76; 95% CI, 0.53 to 5.8; p=0.36). Although the safety profiles were mostly mild, adverse events were more frequent in the 600 mg group, 50% of which requiring dose reduction. Conclusion Alectinib at 300 mg twice daily seems an acceptable dose in East Asians with ALK-positive NSCLC. Notably, our data favor 300 mg twice daily in patients with lower body weight and no baseline brain metastasis, considering the more tolerable safety profiles and the potential to reduce medical costs.

Objective:To validate the role of color Doppler ultrasound in an animal model to detect early heterotopic ossification (HO) after brain-traumatic/burn/tenotomy.Methods:Forty-four rats were randomly divided into two groups. Rats in experimental group ( n=22) were operated to build brain-traumatic/burn/tenotomy model and others in control group ( n=22) underwent only skin incision injury. Color Doppler ultrasound, X-ray film examination at 2, 3, 4, 6, 8 and 10 weeks post-injury were performed to follow up the progression of HO in both groups respectively. Histology was used to confirm bone formation. Results:In the experimental group, disorder structure with a hypoechoiccore in treated Achilles tendon was visualized using color Doppler ultrasound in the 2nd week. Additional tiny hyperechoic foci were observed in the 3rd week, which increased in the fourth week and fused into a mineralized island in the sixth week. No obvious abnormality was found in control group at the aforementioned time point. X-ray could detect heterotopic bone tissue in the sixth week in the experimental group but not in the control group. X-ray and HE stainning had confirmed bone formation in the tenth week in the experimental group.Conclusions:Color Doppler ultrasound can detect early HO and continuously follow up the progression of HO.