Clinical Analysis Of Anaplastic Lymphoma Kinase-positive Non-small Cell Lung Cancer

Objective:ALK-positive lung cancer is a unique subtype of the NSCLCs.To aid in identification and treatment of these patients,we retrospectively reviewed the clinical and imaging characteristics and evaluated the activity and safety of crizotinib in patients with ALK-positive NSCLC.Methods:Patients diagnosed as NSCLC and identified with ALK rearrangement in the First Affiliated Hospital of Zhejiang University between January 1,2013 and February 1,2017 were enrolled.Clinical features were summarized and imaging characteristics were compared between ALK-positive and EGFR-mutated patients.PFSs and ORRs were compared between first-line crizotinib therapy and first-line pemetrexed combined with platinum chemotherapy,as well as between first-line and non-first line crizotinib therapy.Adverse events during the crizotinib course were collected and assessed according to NCI CTCAE.Results:The median onset age of the 129 enrolled patients was 52.Among these patients,72.1%had no smoking history and 96.1%was adenocarcinoma.EGFR mutation was detected in 71 patients and no one was positive.The incidence of venous thromboembolism was 9.7%in phase ⅢB or Ⅳ patients.Most ALK-positive lung cancer patients presented a peripheral(62.7%)solid(87.3%)mass with a spiculated or lobulated contour(94.1%)on chest CT.Multifocal lymphadenopathy was more common(67.1%vs.45.0%,P=0.003),ground-glass opacity or semisolid mass(6.8%vs.29.4%,P<0.001)and bilateral multiple metastases(30.1%vs.51.4%,P=0.005)were less common in ALK-positive patients compared to those EGFR-mutated ones.First-line crizotinib therapy had a longer PFS and a better ORR than first-line pemetrexed combined with platinum chemotherapy(PFS 12.7 months vs.5.6 months,P<0.001;ORR 68.2%vs.26.1%,P=0.001),but had no difference with non-first-line crizotinib therapy(PFS 12.7 months vs.12.8 months,P=0.954;ORR 68.2%vs.60.5%,P=0.470).The cPFS was 7.2 months among patients with brain metastases receiving crizotinib therapy.Radiotherapy and baseline brain metastases were two protective factors of cPFS(HR 0.098,0.154 and 0.336 for gamma knife radiosurgery,whole brain radiotherapy and baseline brain metastases respectively).203 cases of adverse event were collected during the crizotinib course of 84 patients,among which 23 cases were severe,including one rare exfoliative esophagitis case.Only 2 patients with interstitial pneumonia terminated crizotinib therapy.Conclusion:ALK-positive NSCLC patients are more likely to be young,never-smoked,EGFR mutation-negative adenocarcinoma patients combined with venous thromboembolism,and tend to present a peripheral solid mass with a spiculated or lobulated contour and multifocal lymphadenopathy on chest CT.First-line crizotinib therapy has better efficacy than first-line pemetrexed combined with platinum chemotherapy,however,shows no superiority over non-first-line crizotinb therapy.Crizotinib combined with brain radiotherapy can effectively control the brain lesions.Crizotinib shows good safety and is well tolerated in most patients except those with interstitial pneumonia.