ALK rearrangement

P3, N=1200, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting

We outline mechanisms of action, clinical efficacy, and limitations of FDA-approved tyrosine kinase inhibitors (TKIs) and emerging agents, with emphasis on resistance pathways, both on-target and bypass-mediated, observed during treatment with drugs such as osimertinib, crizotinib, sotorasib, and entrectinib. The role of next-generation sequencing (NGS), liquid biopsy, and comprehensive biomarker profiling in guiding personalized therapy selection is also discussed, along with strategies for sequential therapy and rational combination approaches.

The recent developments and acquired knowledge on newer renal entities with eosinophilic cytoplasm opened insights into the clinical, pathological, immunohistochemical, molecular, epidemiological aspects, and the prognosis of these entities. We emphasize the role of routine morphology, aided by appropriate and select immunohistochemistry, as essential keys for diagnosing eosinophilic renal tumours.

Although they account for only about 5% of RCC, they are clinically significant due to distinctive biology, frequent diagnostic pitfalls, and therapeutic implications. Many pathology laboratories lack immediate access to fluorescence in situ hybridization (FISH) or next-generation sequencing (NGS) to confirm MDRC; this review emphasizes morphologic recognition and immunohistochemical surrogates, followed by rational triage for ancillary testing when available.

These findings underscore the importance of routine cardiovascular monitoring, particularly in older patients and those with atrial arrhythmias.

P1/2, N=161, Completed, Takeda | N=109 --> 161

Further analysis revealed that ALK rearrangement was significantly associated with an increased risk of metastasis &lsqb;odds ratio (OR) =2.15; P=0.045], particularly to the bone (OR =5.38; P<0.001) and brain (OR =2.88; P=0.041) after adjusting for confounders. ALK rearrangements were linked to more aggressive histology and increased risk of bone and brain metastases in resected, stage I LUADs, emphasizing the potential relevance of molecular profiling in postoperative risk assessment and treatment planning, even in stage IA patients.

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.