The ALK gene encodes a transmembrane tyrosine kinase receptor. ALK is physiologically expressed in the nervous system during embryogenesis, but its expression decreases postnatally. ALK first emerged in the field of oncology in 1994 when it was identified to fuse to NPM1 in anaplastic large‐cell lymphoma. Since then, ALK has been associated with other types of cancers, including non‐small‐cell lung cancer (NSCLC). More than 19 different ALK fusion partners have been discovered in NSCLC, including EML4, KIF5B, KLC1, and TPR. Most of these ALK fusions in NSCLC patients respond well to the ALK inhibitor, crizotinib. In this paper, we reviewed fusion partner genes with ALK, detection methods for ALK‐rearrangement (ALK‐R), and the ALK‐tyrosine kinase inhibitor, crizotinib, used in NSCLC patients.

AimsTo evaluate the suitability of malignant pleural effusion (MPE) and plasma as surrogate samples for epidermal growth factor receptor (EGFR) mutation detection, and compare three different detection methods.MethodsMatched tissue and plasma samples were collected from patients with advanced non-small cell lung cancer (NSCLC) (stage IIIB/IV adenocarcinoma/adenosquamous carcinoma), with matched MPE samples collected from a subgroup. DNA was extracted from tissue, MPE cell block, MPE supernatant and plasma before mutation detection by amplification refractory mutation system (ARMS) (all samples), Sanger sequencing and mutant-specific immunohistochemistry (IHC) (tissue and MPE cell blocks only).ResultsSensitivity of MPE cell block, MPE supernatant and plasma versus tissue: 81.8% (9/11), 63.6% (7/11) and 67.5% (27/40); specificity was 80.0% (8/10), 100% (10/10) and 100% (46/46), respectively. Sensitivity of Sanger sequencing versus ARMS: 81.8% (27/33) for tissue, 40% (4/10) for MPE cell blocks; specificity was 100% (36/36 and 12/12) for both. Sensitivity of mutant-specific IHC versus ARMS: 54.8% (17/31) for tissue, 50.0% (6/12) for MPE cell blocks; specificity was 97.1% (34/35) and 100% (14/14), respectively.ConclusionsMPE and plasma are valid surrogates for NSCLC tumour EGFR mutation detection when tissue is not available. ARMS is most suitable for mutation detection in tissue and MPE cell blocks; however, mutant-specific IHC could be a complementary method when DNA-based molecular testing is unavailable.

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Circular RNAs (circRNAs) are a new class of RNAs, and many studies have identified thousands of circRNAs in tumor cells. Fibronectin type III domain‐containing protein 3B (FNDC3B) circular RNA (circFNDC3B, circBase ID: hsa_circ_0006156) circularizes with exons 5 and 6. Gibson Assembly DNA technology was used to construct a circFNDC3B expression vector without a splice site and restriction enzyme site. We showed that circFNDC3B increased migration and invasion in gastric cancer (GC). Ectopic expression of circFNDC3B reduced the level of E‐cadherin protein to promote the epithelial–mesenchymal transition in GC. RNA immunoprecipitation assays and RNA pull‐down assays confirmed that circFNC3B increased CD44 expression, which was associated with cell adhesion, via the formation of a ternary complex of circFNDC3B‐IGF2BP3‐CD44 mRNA. These results indicated that circFNDC3B was associated with the degree of malignancy to highlight the specific characteristics of cell invasion.

Background: The role of 18 fludeoxyglucose ( 18 F-FDG) PET/CT in the management of limited stage small-cell lung cancer (LS-SCLC) is uncertain. Previous studies have shown that 18 F-FDG PET/CT upstages up to 30% of LS-SCLC patients. Data from the CONVERT trial was analysed to investigate the impact of 18 F-FDG PET/CT in the management of LS-SCLC. The prognostic significance of pre-treatment 18 F-FDG PET parameters was also investigated in an exploratory analysis. Method: CONVERT is an international multi-centre phase III trial that randomly assigned fit patients to receive either twice-daily (45Gy in 30 fractions) or once-daily (66Gy in 33 fractions) radiotherapy starting on day 22 of chemotherapy cycle 1 (NCT00433563). Chemotherapy consisted of 4-6 cycles of cisplatin and etoposide. Prophylactic cranial irradiation was offered, if indicated. Contrast-enhanced thorax and abdomen CT and brain imaging (with/ without bone scintigraphy according to clinical indication) were mandated for all CONVERT participants (conventional imaging). Staging with 18 F-FDG PET/CT was allowed but not mandated. The primary endpoint was overall survival. Pre-treatment 18 F-FDG PET metabolic parameters were investigated in a subset of patients (n¼96) including standardised uptake values (max, mean and peak), volumetric and heterogeneity parameters. Result: Of 547 patients recruited to CONVERT, 540 patients with data on staging investigations and outcome were included in this analysis. The use of staging 18 F-FDG PET/CT was variable in the 8 countries recruiting to CONVERT (range, 41-100%). Compared to patients who underwent conventional imaging (n¼231), patients who were also staged with 18 F-FDG PET/CT (n¼309) had smaller gross tumour volume (p¼0$003), were less likely to have elevated pre-treatment serum lactate dehydrogenase (p¼0$035), and received more chemotherapy cycles (p¼0$026). There were no other significant differences in baseline and treatment characteristics between the two groups. There were no significant differences in overall (hazard ratio 0$87 [95% CI 0$70-1$08]; p¼0$192) and progression-free survival (hazard ratio 0$87 [95% CI 0$71-1$07]; p¼0$198) between patients staged with 18 F-FDG PET/CT in addition to conventional imaging or with conventional imaging alone. These results were observed irrespective of treatment group (once-daily and twice-daily radiotherapy). Pre-treatment 18 F-FDG PET parameters were also not prognostic. Conclusion: In CONVERT, survival outcomes were not different in LS-SCLC patients staged with or without 18 F-FDG PET/CT. This was despite those patients staged with 18 F-PET/CT having more favourable baseline and treatment characteristics. Our findings suggest that conventional imaging is sufficient to select LS-SCLC patients for concurrent chemoradiotherapy.Background: The interim analysis of our prospective trial, which compared irradiation to pre-chemotherapy or post-chemotherapy tumour extent while application of involved field radiotherapy (IFRT) for limited-stage small cell lung cancer (SCLC...