<scp>ALK</scp>‐rearranged squamous cell carcinoma of the lung

Meng, Qingduan; Dong, Yujie; Hong, Tao; Shi, Liang; Li, Tong; Tang, Jiaguang; Zhang, Shucai; Liu, Zhe

doi:10.1111/1759-7714.13818

Cited by 12 publications

(10 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ALK LUSC outcome is especially inferior compared with ALK LUAD, consistent with multiple previous studies that reported LUSC harboring an EML4-ALK rearrangement were unsuccessfully treated with ALK TKI. 15 The therapeutic effect of ALK TKI in patients with LUSC remains controversial.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Targeted Inhibitors in Metastatic Lung Squamous Cell Carcinoma With EGFR or ALK Alterations

Lewis

Hong

Mott

et al. 2021

JTO Clinical and Research Reports

View full text Add to dashboard Cite

Introduction The efficacy of targeted therapies in oncogene-driven lung adenocarcinomas (LUADs) has been well established; however, the benefit for EGFR -mutant or ALK -rearranged lung squamous cell carcinomas (LUSCs) is less known, partially owing to the rarity of the incidence. Methods We reviewed the database of the MD Anderson Cancer Center and identified metastatic LUSC with classic EGFR or ALK alterations. Results There were eight patients with EGFR -mutant LUSC (median age = 58 y) and six patients with EML4-ALK LUSC (median age = 50 y) who received tyrosine kinase inhibitors (TKIs) that were identified. Of the 14 patients, 11 (79%) were females and 12 (86%) were never smokers, similar to the demographics of EGFR or ALK LUAD. With TKI treatment, seven of eight cases of EGFR LUSC and four of six cases of ALK LUSC achieved partial response or stable disease, but the progression-free survival was 4.9 months and 2.9 months for EGFR -mutant and ALK -rearranged LUSC, respectively. In addition, we compared comutation profile of EGFR -mutant LUAD (The Cancer Genome Atlas, n = 46) versus LUSC (n = 19) and found that the comutation patterns are more consistent with squamous disease with a higher incidence of PIK3CA ( p = 0.02) and KRAS or BRAF ( p = 0.04) alterations. Conclusions EGFR or ALK alterations occur in patients with LUSC, especially never-smoker females. TKI treatments render clinical benefit in disease control, but the duration was considerably truncated compared with those historically observed in LUAD.

show abstract

Section: Discussionmentioning

confidence: 99%

Efficacy of Targeted Inhibitors in Metastatic Lung Squamous Cell Carcinoma With EGFR or ALK Alterations

Lewis

Hong

Mott

et al. 2021

JTO Clinical and Research Reports

View full text Add to dashboard Cite

show abstract

“…presented a single-center case review of 31 ALK-positive LSCC patients, of whom 20 received ALK-TKIs as their initial or subsequent treatment. The median PFS in this group was 6.4 months ( ± 4.4 months), notably shorter than that observed in ALK-positive LADC patients treated with ALK inhibitors ( 10 ). Lu et al.…”

Section: Discussionmentioning

confidence: 52%

Case report: Clinical complete response in advanced ALK-positive lung squamous cell carcinoma: a case study of successful anti-PD-1 immunotherapy post ALK-TKIs failure

Yang,

Zeng,

Zha

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

In patients with advanced lung adenocarcinoma (LADC) harboring the echinoderm microtubule-associated protein-like 4 (EML4) -anaplastic lymphoma kinase (ALK) rearrangement, targeted therapy typically demonstrates superior efficacy as an initial treatment compared to chemotherapy. Following resistance to ALK-tyrosine kinase inhibitors (TKIs), regimens incorporating platinum-based dual agents or combined with bevacizumab often show effectiveness. However, therapeutic alternatives become constrained after resistance develops to both TKIs and platinum-based therapies. Given that the majority of ALK-positive non-small cell lung carcinomas (NSCLC) are LADC, the benefits of TKIs for patients with ALK-positive lung squamous cell carcinoma (LSCC) and the optimal treatment strategy for these patients remain a subject of debate. In this case study, we report on a patient with advanced LSCC, in whom the EML4-ALK rearrangement was identified via ARMS-PCR (Amplification Refractory Mutation System-Polymerase Chain Reaction). The patient underwent oral treatment with crizotinib and alectinib, showing effectiveness in both first-line and second-line ALK-TKI therapies, albeit with limited progression-free survival (PFS). Subsequent resistance to second-generation TKI was followed by the detection of tumors in the left neck region via computed tomography (CT). Biopsy pathology revealed non-squamous cell carcinoma, and subsequent treatment with platinum-based double-drug therapy proved ineffective. Further analysis through next-generation sequencing (NGS) indicated ALK negativity but a high expression of programmed death-ligand 1 (PD-L1). Immunotherapy was then initiated, resulting in a PFS of over 29 months and clinical complete remission (cCR). This case underscores the potential benefit of ALK-TKIs in patients with ALK-positive LSCC. Resistance to second-generation TKIs may lead to ALK negativity and histological transformation, highlighting the necessity of repeated biopsies post-TKI resistance for informed treatment decision-making. As of November 2023, imaging studies continue to indicate cCR in the patient, with a survival time exceeding 47 months.

show abstract

“…Clinically, the ALK rearranged SQCC patients also obtained benefit from ALK -TKIs, but was not as beneficial as compared to the ADC patients ( 21 , 22 ). In this case, different therapeutic effects of ALK -TKI treatment were observed in two different morphological sites.…”

Section: Discussionmentioning

confidence: 88%

Case Report: Response to ALK-TKIs in a metastatic lung cancer patient with morphological heterogeneity and consistent molecular features

Liang

Liu

et al. 2023

Front. Oncol.

View full text Add to dashboard Cite

Lung adenosquamous carcinoma (ASC) is a rare heterogeneous tumor containing two distinct components of adenocarcinoma (ADC) and squamous cell carcinoma (SQCC). The limited biopsy sampling of the primary tumor might have overlooked either the ADC component or the SQCC component, resulting in a misdiagnosis of pure histology. Genotyping for driver mutations is now routinely performed in clinical settings to identify actionable oncogenic mutations and gene arrangements. Additionally, somatic mutations can potentially serve as a marker of clonal relationships. We report a rare case of ASC lung cancer, in which metastases were identified as ADC, while the primary was initially diagnosed as SQCC based on a fibrobronchoscope brush biopsy. The primary and metastatic tumors shared ALK rearrangement and other mutations support they were derived from a single clone origin. Our hypothesis is that the primary tumor contained a minor component of ADC that was not present in the histologic sections of lung biopsy. After sequential ALK-tyrosine kinase inhibitor (TKI) targeted therapy, both the patient’s primary lung tumor and the site of metastatic subcutaneous nodules decreased in size, with the metastatic sites demonstrating more noticeable shrinkage. However, after 11 months of targeted therapy, the patient was found to be resistant to ALK-TKIs. Subsequently, the patient’s respiratory status deteriorated rapidly, and a cycle of immunotherapy and chemotherapy did not show efficacy. To the best of our knowledge, this is a very rare case of lung ASC, disseminated metastasizing, with distinct morphology between the primary and metastases. Different therapeutic effects of ALK-TKIs were observed in two different morphological sites, with the metastatic cutaneous lesions shrinking more significantly than the primary lung lesions, though they both harbor the same EML4-ALK rearrangement. This case may provide diagnostic and therapeutic insights into lung ASC.

show abstract

ALK‐rearranged squamous cell carcinoma of the lung

Cited by 12 publications

References 34 publications

Efficacy of Targeted Inhibitors in Metastatic Lung Squamous Cell Carcinoma With EGFR or ALK Alterations

Efficacy of Targeted Inhibitors in Metastatic Lung Squamous Cell Carcinoma With EGFR or ALK Alterations

Case report: Clinical complete response in advanced ALK-positive lung squamous cell carcinoma: a case study of successful anti-PD-1 immunotherapy post ALK-TKIs failure

Case Report: Response to ALK-TKIs in a metastatic lung cancer patient with morphological heterogeneity and consistent molecular features

Contact Info

Product

Resources

About