ALK positive

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

Treatment procedures are rapidly evolving, but the clinical presentations of these diseases remain unchanged. The disease profiles presented in this publication should aid in their early diagnosis and consequently in timely treatment.

The patient was treated with brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisone, following which the febrile episodes improved. This case illustrates an uncommon gastrointestinal-predominant presentation of ALK-negative systemic ALCL presenting as fever of unknown origin. This case underscores the importance of continued diagnostic reassessment and symptom-guided tissue acquisition when conventional staging studies are not initially diagnostic, particularly in patients with a history of indolent lymphoma.

In this real-world Vietnamese cohort, first-line alectinib showed superior intracranial and systemic efficacy over ceritinib. In resource-limited settings, ceritinib combined with upfront brain RT is a reasonable clinical alternative. The differential benefit of brain RT between the two TKIs remains hypothesis-generating.

This case highlights the possibility that alectinib may impair postoperative wound repair. Comprehensive perioperative drug evaluation, multidisciplinary collaboration, and carefully monitored treatment interruption are recommended to maintain the balance between oncologic control and effective tissue healing.

Despite the lack of formal evidence for alternative formulations, pharmacokinetic data suggest adequate absorption. Crushed lorlatinib administered through a nasogastric tube represents a practical and effective option for dysphagic patients with ALK-positive NSCLC requiring early target-directed therapy.

While second- and third-generation ALKi (including alectinib, brigatinib, ensartinib, envonalkib, and lorlatinib) have demonstrated superior efficacy compared with the first-generation inhibitor crizotinib in randomized trials, the absence of direct head-to-head comparisons limits the definition of their relative clinical benefit. This indirect comparison indicates that lorlatinib provides the most durable PFS and the strongest intracranial disease control, although ALKis are characterized by distinct toxicity profiles. In the absence of clear OS differences at present, first-line treatment selection should integrate efficacy, intracranial activity, tolerability, and emerging molecular features within a personalized therapeutic framework.

Moreover, ISZ-sTRAIL induced caspase-dependent apoptosis in both cell lines via activation of extrinsic and intrinsic pathway, and these effects were markedly abrogated by the pan-caspase inhibitor Z-VAD. These findings identify DR4/DR5 as a potential therapeutic target and provide preclinical evidence for the development of TRAIL-based strategies in the treatment of EML4-ALK-positive NSCLC.

Current evidence suggests a possible oncogenic interaction between hereditary susceptibility and chronic implant-associated inflammation. Clinicians must maintain vigilance for BIA-ALCL even in prophylactic settings, as early diagnosis and complete surgical excision remain key to favorable outcomes.

Tumor burden was prognostic and predictive in ALK-positive NSCLC. Treatment intensification may benefit patients with high tumor burden.

Our case provided evidence that locally advanced, ALK-positive LSCC could benefit from neoadjuvant ensartinib, with an impressive response and favorable safety. Our findings may also extend the indications for targeted therapy to the neoadjuvant setting in locally advanced, ALK-positive, resectable LSCC.

This first documented case demonstrates the therapeutic efficacy of crizotinib in ALK-IR rearranged NSCLC, emphasizing the importance of comprehensive molecular profiling in guiding precision oncology.