ALK positive

Crizotinib showed no significant difference in progression-free survival (PFS) or overall survival (OS) between first-line and post-chemotherapy use (PFS: p = 0.803; OS: p = 0.761). For second-generation ALK-TKIs, first-line treatment had numerically longer PFS compared to post-chemotherapy (alectinib: 41 vs 24 months; ceritinib: 30 vs 8 months), but these differences were not statistically significant after adjustment (p = 0.120 and 0.284, respectively)...Among patients treated with alectinib, there appears to be a trend toward shorter PFS and OS in those with MET overexpression. In a limited number of matched samples, PD-L1 expression did not change significantly after TKI resistance, although a slight increase was observed.

ALK inhibitors, including crizotinib, ceritinib, alectinib, brigatinib, and lorlatinib has significantly improved clinical outcomes in ALK-rearranged NSCLC patients. To overcome these resistance mechanisms, the development of novel therapeutic strategies are required. By integrating structural biology, mutation evolution patterns, and emerging therapeutic approaches, this review underscores the need for next-generation inhibitors to overcome resistance and improve long-term outcomes in patients with ALK-positive NSCLC.

Since the approval of crizotinib, which was the first ALK tyrosine kinase inhibitor (TKI), the treatment landscape has rapidly evolved with the development of multiple next-generation TKIs and investigational agents...However, CNS progression, acquired resistance, and optimal treatment sequencing continue to limit outcomes. This review synthesizes current evidence to guide clinical practice and future investigations.

P4, N=29, Not yet recruiting, Hunan Cancer Hospital

After an uneventful 5-day hospitalization without complications, the patient remains disease-free at the 12-month follow-up. This is the first report of neoadjuvant lorlatinib followed by uniportal VATS achieving pCR predicted by CMR in stage IIIB ALK-positive NSCLC, given the limitations of short-term follow-up and a single-case design.

Next-generation sequencing and fluorescence in situ hybridization confirmed the EWSR1 (exon 15)::CREM (exon 6) fusion in both cases. These uterine neoplasms broaden the spectrum of malignant epithelioid neoplasms and should be included in the differential diagnosis of epithelioid neoplasms involving the female reproductive system.

Transcriptomic analyses identified PIP5K1C as a downstream effector regulated through a competitive endogenous RNA mechanism in which circZBTB46 acts as a sponge to miR-25-3p, alleviating its repression of PIP5K1C. These findings uncover a previously unrecognized mechanism of drug resistance in ALK( + ) ALCL and establish circZBTB46 as a promising therapeutic target.

P4, N=80, Not yet recruiting, Qiming Wang

She received alectinib combined with CNS-directed chemotherapy and has remained in complete remission for 20 months on alectinib maintenance. These cases suggest that alectinib, combined with CNS-directed chemotherapy, is effective in both ALK-positive ALCL with CNS relapse and primary isolated CNS disease.

This multinational registry-based analysis highlights evolving global treatment patterns, supports newer TKIs' effectiveness, and identifies clinical and molecular factors associated with treatment duration.

Postoperative recovery was uneventful, with no recurrence observed during a 6-month follow-up period. This case highlights an unusual presentation of EFH in a pediatric eyelid, where a rare tumor that occurred in the eyelid of a 7-year-old child was accurately diagnosed through a set of immunohistochemical panels containing tissue cell markers (CD68 and CD163), melanoma cell markers (S-100), dendritic cell markers (CD1a), mesenchymal cell markers (CD10) and ALK.

P2, N=118, Completed, Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest | Active, not recruiting --> Completed