Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Clinical Challenge of Two Competing Targetable Mutations in Non-Small-Cell Lung Cancer: A Case Report.

ABSTRACT: The development of therapeutic agents targeting products of epidermal growth factor receptor (EGFR) gene mutation and anaplastic lymphoma kinase (ALK) rearrangements has improved survival in patients with non-small-cell lung cancer. EGFR and ALK mutations are generally regarded as mutually exclusive, and the presence of one in lieu of another influences the response to targeted therapy. We herein present an interesting case following the course of progression of a patient with synchronous lung cancers with a discordant mutation profile. The importance of this modality in the follow-up of lung cancer patients is illustrated, and the therapeutic implications of coexisting oncogenic drivers are briefly discussed.

SUBMITTER: Park SY

PROVIDER: S-EPMC10572277 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Clinical Challenge of Two Competing Targetable Mutations in Non-Small-Cell Lung Cancer: A Case Report.

Park Sonya Youngju SY Yoon Hyukjin H Han Eun Ji EJ Yoo Ie Ryung IR

Diagnostics (Basel, Switzerland) 20231002 19

The development of therapeutic agents targeting products of epidermal growth factor receptor (EGFR) gene mutation and anaplastic lymphoma kinase (ALK) rearrangements has improved survival in patients with non-small-cell lung cancer. EGFR and ALK mutations are generally regarded as mutually exclusive, and the presence of one in lieu of another influences the response to targeted therapy. We herein present an interesting case following the course of progression of a patient with synchronous lung c ...[more]

PMID: 37835855

Similar Datasets

New targetable oncogenes in non-small-cell lung cancer.

Project description:The identification of oncogenic driver mutations underlying sensitivity to epidermal growth factor receptor and anaplastic lymphoma kinase tyrosine kinase inhibitors has led to a surge of interest in identifying additional targetable oncogenes in non-small-cell lung cancer. A number of new potentially oncogenic gene alterations have been characterized in recent years, including BRAF mutations, HER2 insertions, PIK3CA mutations, FGFR1 amplifications, DDR2 mutations, ROS1 rearrangements, and RET rearrangements. In this review, we will discuss the techniques used to discover each of these candidate oncogenes, the prevalence of each in non-small-cell lung cancer, the preclinical data supporting their role in lung cancer, and data on small molecular inhibitors in development.

| S-EPMC3589703 | biostudies-literature

Case report: Two novel intergenic region-ALK fusions in non-small-cell lung cancer resistant to alectinib: A report of two cases

Project description:Background The anaplastic lymphoma kinase (ALK) mutation, also known as the diamond mutation in non–small-cell lung cancer (NSCLC), has been treated with tremendous success since it was first reported in 2007. Alectinib, a second generation ALK-Tyrosine kinase inhibitor (TKI), has been reported to have significantly longer progression- free survival (PFS) than first generation ALK inhibitors in untreated ALK positive NSCLC. However, the clinical efficacy of ALK-TKIs on rare ALK fusions remains unclear. In recent years, with the popularity of next-generation sequencing (NGS) technology, an increasing number of novel ALK fusion partners have been reported, but the responses are heterogeneous among different ALK fusions. Considering the inconsistent reactions, the clinical efficacy of ALK-TKIs in rare ALK gene fusions remains to be evaluated in more cases. Methods To seek for individualized therapy, the tumor tissues acquired during biopsy were sent for genomic testing by NGS based on a 139-gene panel and a 425-gene panel in a centralized clinical testing center (GENESEEQ Technology Inc, Nanjing, China). See Supplementary Material for more details about the methods for DNA-based NGS, RNA-based NGS. Results We present two cases of patients with lung adenocarcinoma harboring two novel Intergenic Region (IGR)-ALK rearrangements detected by DNA sequencing, which had limited clinical response to ALK-TKIs but showed sensitivity to chemotherapy combined with bevacizumab therapy in patient 2, with a PFS of over 1 year up till the last follow‐up assessment. Conclusions In summary, our cases emphasize the need for comprehensive molecular analysis of different ALK fusion partners at the DNA level to formulate accurate treatment strategies and provide a certain therapeutic reference for these two types of novel IGR-ALK fusions.

| S-EPMC9356229 | biostudies-literature

Case report: Pulmonary Ewing sarcoma disguised as non-small cell lung cancer.

Project description:Ewing sarcoma is the second most common primary malignant bone cancer in children and adolescents. This rare type of cancer is characterized by its high malignancy and therefore high risk of metastases. Typically, Ewing sarcomas originate from bones. However, extraosseous Ewing sarcoma such as pulmonary Ewing sarcoma can also be found. In this case report, we present a 55-year old male patient who was initially diagnosed with non-small cell lung cancer at his local district hospital. However, the diagnosis was changed to one of pulmonary Ewing sarcoma after subsequent histopathological and molecular pathological analysis performed in a reference pathology laboratory. After patient referral to a certified (according to the German Cancer Society) high-volume sarcoma center, multimodal chemotherapy was initiated based on recently published clinical data as opposed to the more commonly used treatment regimen in Europe. The patient responded well to treatment and underwent a complete surgical tumor resection followed by radiotherapy. In summary, this case report highlights the importance of a rigorous and timely histopathological examination of biopsy samples by a specialized cancer center to enable a correct diagnosis of the cancer type. Additionally, molecular pathology plays a crucial part in this analysis and allows the necessary differentiation between cancer types. Up to now, there is no international treatment guideline available for the treatment of Ewing sarcoma. Patients should be referred to specialist centers to allow the best possible treatment of the cancer type in view of current published clinical data. In the case of Ewing sarcoma, and in accordance with the most recent research, patients should be treated with vincristine, doxorubicin and cyclophosphamide plus ifosfamide and etoposide in combination with local treatment such as surgery and/or radiotherapy because this has been demonstrated to be the more effective therapy.

| S-EPMC11578818 | biostudies-literature

Efficacy and safety of immune checkpoint inhibitors for advanced non-small cell lung cancer with leptomeningeal metastases harboring targetable mutations.

Project description:BackgroundDriver gene-positive non-small cell lung cancer (NSCLC) patients are prone to develop leptomeningeal metastasis (LM), leading to an extremely high mortality. The objective of this study was to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) treatments for patients with NSCLC and LM harboring targetable mutations.MethodsWe retrospectively collected records of patients with NSCLC harboring targetable mutations and prescribed ICIs following the diagnosis of LM at Huashan Hospital, Fudan University. In addition, we reviewed relevant literature and enrolled patients who met the inclusion criteria. Clinical characteristics were statistically analyzed, and the Kaplan-Meier method and log-rank test were employed to assess the median progression-free survival (mPFS) and median overall survival (mOS).ResultsA total of 37 patients with NSCLC harboring targetable mutations who received ICIs after LM diagnosis were included. The median age of the enrolled patients was 54 years (range, 33-70 years), and 62.2% were female. Following ICI administration, the intracranial objective response rate (iORR) and intracranial disease control rate (iDCR) for all enrolled patients were 18.9% and 62.2%, respectively. The mPFS of all patients was 2.5 months [95% confidence interval (CI): 2.166-2.834 months] and the mOS was 5.8 months (95% CI: 5.087-6.513 months). Both univariate and multivariate analyses revealed a significant increase in mOS or individuals who had previously undergone cranial radiation therapy compared to those who had not. Furthermore, different histology molecular types were found to be potentially associated with survival time.ConclusionsSome patients with NSCLC harboring targetable gene mutations following LM diagnosis may benefit from ICI treatment with relatively good tolerance. However, further screening of the most suitable patient populations for ICIs is required.

| S-EPMC11304138 | biostudies-literature

Complex Germline K757N Mutation in Non-Small-Cell Lung Cancer: A Case Report.

Project description:Epidermal growth factor receptor (EGFR) mutations are usually oncogenic drivers of lung tumor development and progression. While common sensitizing mutations respond well to targeted therapy, the relevance of germline EGFR mutations is less clear. We describe a 65-year-old, previously healthy, male diagnosed with non-small-cell lung cancer. Familial history for lung cancer is negative. Targeted next-generation sequencing on the tumor biopsy sample revealed an atypical EGFR K757N mutation at 50% allele frequency and genetic review of a previously acquired gastric sample confirms the mutation as a germline change. He received standard first-line chemoimmunotherapy with carboplatin, pemetrexed, and pembrolizumab, and after 8 months therapy continues, with stable disease, to receive maintenance pemetrexed and pembrolizumab. To our knowledge, this is the first report of an atypical, germline K757N EGFR mutation. While the clinical relevance of this mutation is unclear, standard reporting of the allelic frequency of novel, atypical mutations can detect potential germline changes.

| S-EPMC9035954 | biostudies-literature

Non-small cell lung cancer with MET exon 14 skip mutation: case report.

Project description:BackgroundNon-small cell lung cancer (NSCLC) is the most common type of lung cancer, making up 80-85% of all lung malignancies. It can be further subdivided into different types. The three main subtypes are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Traditionally, NSCLCs have been treated with a combination of chemotherapy, surgery, and/or radiation therapy. However, with the advent of genotype subtype analysis and targeted therapy it has become possible to have individualized treatment options for patients with NSCLC.Case descriptionWe present a case report of a 68-year-old female with NSCLC. Patient initially only received radiation therapy due to her not being a surgical candidate. While initial treatment was responsive, later imaging showed metastasis of disease. Subsequent genotype analysis of the patient's tumor indicated a MET exon 14 skipping mutation which qualified her for treatment with Capmatinib (Tabrecta).ConclusionsPatients on Capmatinib have minimal side effects and better efficacy than traditional chemotherapy. Patients with MET exon 14 skipping mutations should be considered for Capmatinib therapy.

| S-EPMC9816822 | biostudies-literature

SMARCA4‐deficient non‐small cell lung cancer with an EGFR mutation: A case report

Project description: Not available

| S-EPMC10623088 | biostudies-literature

Alectinib-associated pneumoperitoneum in stage IV non-small cell lung cancer - A case report.

Project description:Introduction and importanceAlectinib, a highly potent, highly selective, brain-penetrant anaplastic lymphoma kinase (ALK) inhibitor is now the first line therapy for patients with metastatic ALK-positive non small cell lung cancer (NSCLC).Case presentationWe report a rare case of pneumoperitoneum following alectinib initiation for metastatic non small cell lung cancer in a 74-year-old African American female. Patient developed abdominal pain approximately 2 weeks after starting alectinib. She was hemodynamically stable, and imaging revealed pneumoperitoneum. Patient was successfully managed non-operatively.Clinical discussionGastrointestinal perforation presenting as pneumoperitoneum is a very rare complication of alectinib. To our knowledge our patient is only the second case to be reported in the literature since its approval. The complication is likely attributable to the rapid tumor regression in the gastrointestinal tract. Non-operative management should be attempted if possible.ConclusionOncologists should be aware of the risk of gastrointestinal perforation when initiating cytotoxic chemotherapy on patients with metastatic NSCLC. A multidisciplinary approach is critical in appropriately individualizing care in this patient population.

| S-EPMC9577531 | biostudies-literature

Takotsubo cardiomyopathy Afatinib-related in a non-small cell lung cancer patient: Case report.

Project description:Endothelial Growth Factor Receptor (EGFR) mutations are frequently found among NSCLC patients. Second-generation Tyrosine Kinase Inhibitor (TKI) Afatinib is frequently used in this population of patients achieving better results than cytotoxic chemotherapy in terms of survival and progression. Afatinib-related cardiotoxicity has been rarely reported. Here we comment on a clinical case of a Takotsubo Cardiomyopathy Afatinib-induced in an NSCLC patient.

| S-EPMC9724619 | biostudies-literature

Genomic profiling of CD20 negative diffuse large B cell lymphoma identifies targetable mutations: A case report.

Project description: Not available

| S-EPMC9175822 | biostudies-literature