The Presence of ALK Alterations and Clinical Relevance of Crizotinib Treatment in Pediatric Solid Tumors

Abstract

Soft tissue sarcomas (STS) and neuroblastomas (NBL), are childhood malignancies still associated with poor prognoses despite the overall improvement in childhood tumor survival of the past decades. Anaplastic lymphoma kinase (ALK) inhibition is promising new strategy to improve the outcome of these pediatric tumors. Eighteen histologic samples of pediatric STS and 19 NBL patients were analyzed for ALK abnormalities using fluorescent in situ hybridization (FISH) with break-apart probes and immunohistochemistry (IHC). ALK alterations were presented in 20 of the 37 sections. The presence of ALK alteration in NBL samples were detected using IHC in 84,2% of all cases compared to 21,1% FISH positivity. In STS cases the results were less different (IHC 16,7% vs FISH 22,2%). The difference can be explained by the different type of molecular alterations. FISH method detected translocation and amplification, but not the point mutation of ALK gene. IHC confirmed the diagnosis by detecting the expression of ALK protein.After ALK positivity was proven, the effectiveness and safety of the crizotinib therapy was examined in 4 patients (1 alveolar rhabdomyosarcoma (RMA), 1 embryonal rhabdomyosarcoma (RME), 1 inflammatory myofibroblastic tumor (IMT), 1 NBL). We observed continuous remission of the IMT patient, all other cases the inhibitor treatment was not curative.Our findings underline the importance of screening the ALK status parallel with both IHC and FISH. Crizotinib treatment had a long-term effect in ALK positive IMT patients, however itwas only temporary efficient in relapsed, progressive STS and NBL.

Extrapleural Pneumonectomy for Sarcoma of the Lung in a Pediatric Patient

“… 7 The reported case is particularly interesting and innovative because molecular pathology confirmed ALK-EML4 translocation opening up the possibility for targeted therapy with a proteinase inhibitor. 8 As a consequence, the applied systemic therapy was from the outset combining conventional chemotherapy with targeted drugs as crizotinib.…”

Organ-associated pseudosarcomatous myofibroblastic proliferation with ossification in the lower pole of the kidney mimicking renal pelvic carcinoma: A case report

“…If conservative treatment is ineffective, simple tumor resection or partial nephrectomy would be feasible. It was recently reported that Myofibroblastic tumour patients had promising results with crizotinib treatment, so tyrosine kinase inhibitors (TKIs) can be used as an alternative to conservative treatment[13,14]. For tumors that are difficult to completely resect, TKIs can be also used as neoadjuvant therapy.…”

Cytologic Diagnosis of Metastatic Alveolar Rhabdomyosarcoma in Cerebrospinal Fluid: A Case Report

“…Crizotinib is approved for the treatment of ALK -rearranged non-small cell lung cancer, but the majority of ALK gene aberration in RMS is copy number gain [ 16 ]. There are limited clinical trial data on the effect of crizotinib on ALK-positive RMS and its efficacy on RMS requires further investigation [ 17 ].…”