ALK rearrangement

Here, we present the case of a patient with advanced HER2 mutant NSCLC who achieved complete pathologic response to chemoimmunotherapy. Our observation suggests that not all driver mutations equally drive resistance to immunotherapy, and some molecular events, such as HER2 mutations, need additional investigations.

The index case report highlights the diagnostic complexities of the small cell variant of ALCL and emphasises the utility of various ancillary techniques like immunophenotyping and FISH, in conjunction with cytomorphology, in confirming such a challenging diagnosis.

P4, N=136, Recruiting, Nikolaj Frost MD | Trial primary completion date: Oct 2025 --> Feb 2026

Among the patient-reported outcomes, different domains of quality of life improved. This case may represent the backbone for further interventional studies aimed at determining the real efficacy of exercise intervention in preventing or controlling weight gain in this population.

Our validation study shows that overly sensitive ALK IHC assays could result in false-positive tumours presenting with difficult-to-read focal or diffusely weak immunoreactivity, which could lead to potential overuse of confirmatory molecular tests. We therefore recommend carefully fine-tuning ALK IHC assays with the D5F3 clone by comparing diagnostic performance with molecular data.

The addition of serplulimab to chemotherapy led to significantly longer progression-free survival in patients with locally advanced or metastatic non-squamous NSCLC compared with chemotherapy alone and represents an alternative first-line treatment option for this patient population. HLX04 plus serplulimab and chemotherapy did not confer further statistical benefit compared with serplulimab plus chemotherapy.

P1, N=40, Recruiting, University Health Network, Toronto | Trial primary completion date: Dec 2025 --> Aug 2026

These results, along with the extended intracranial efficacy and consistent safety profile of long-term lorlatinib treatment, are unprecedented in patients with ALK-positive mNSCLC. This Grand Rounds article summarizes the efficacy, safety, and tolerability of lorlatinib after 5 years and includes a fictional patient case to demonstrate how advanced practice providers contribute to personalized patient care and the identification and management of adverse events.

Currently, molecular analyses guide treatment decisions in advanced cases following discussions in molecular tumour boards. Therefore, the classification of subtypes, together with their specific molecular alterations and signalling pathways, is gaining importance not only for targeted systemic therapy but also for the identification of patients with a hereditary tumour syndrome.The task of pathologists is to identify new tumour entities and genetically inherited tumour forms in order to ensure the best possible clinical care for patients.

These findings suggest that targeted therapy for recurrence is a valuable treatment strategy. Prospective studies are warranted to determine the optimal timing for ALK-TKI initiation.

Biomarker discovery advances with a new assay enabling the use of miRNAs for non-invasive diagnosis and staging of metabolic dysfunction-associated steatotic liver disease (MASLD). Finally, an optimized elastase assay improves FISH-based detection of ALK gene rearrangements, enhancing diagnostic accuracy in non-small cell lung cancer (NSCLC).

The first metastatic site in NSCLC follows histology-specific patterns, with adenocarcinoma favoring hematogenous spread and squamous carcinoma showing locoregional involvement. Molecular status further refines these patterns in adenocarcinoma. Incorporating histology into baseline staging may improve diagnostic efficiency and prognostic accuracy.