Circulating Cell-free DNA as a Prognostic Biomarker in Patients with Advanced ALK+ Non-small Cell Lung Cancer in the Global Phase III ALEX Trial

Introduction: We retrospectively assessed prognostic value of circulating cell-free DNA (cfDNA) using data from the phase III ALEX study in treatment-naïve, advanced ALK+ NSCLC. Methods: Patients were randomized to receive twice-daily alectinib 600 mg (n = 152) or crizotinib 250 mg (n = 151). cfDNA was quantified from baseline plasma samples, with patients stratified into {less than or equal to}median and >median cfDNA biomarker-evaluable populations (BEP). Effect of cfDNA concentration on outcomes was analyzed using a Cox regression model with treatment group as covariate, and in multivariate analyses. Results: Median cfDNA concentration in the BEP was 11.53 ng/mL (n = 276). A positive correlation was found between cfDNA concentration and number of lesions, organ lesion sites, and tumor size (sum of longest diameter; all p<0.0001). In both treatment arms, patients in the >median BEP were more likely to experience disease progression than the {less than or equal to}median BEP (alectinib adjusted hazard ratio [HR] 2.04 [95% confidence interval (CI): 1.07-3.89], p=0.0305; crizotinib adjusted HR 1.83 [95% CI: 1.11-3.00], p=0.0169). Median progression-free survival was longer with alectinib than crizotinib in both {less than or equal to}median and >median BEPs (p<0.0001). Overall survival data remain immature; survival probability was lower in the >median versus {less than or equal to}median BEP in both treatment arms (alectinib HR 2.52 [95% CI: 1.08-5.88], p=0.0333; crizotinib HR 2.63 [95% CI: 1.27-5.47], p=0.0096). Conclusion: These data suggest that plasma cfDNA concentration may have prognostic value in advanced ALK+ NSCLC. Prospectively designed studies are warranted to investigate this finding. READ ARTICLE

Clinical Cancer Research DOI:10.1158/1078-0432.CCR-21-2840

Authors: Rafal Dziadziuszko, Solange Peters, Tony Mok, D. Ross. Camidge, Shirish M. Gadgeel, Sai-Hong Ignatius. Ou, Krzysztof Konopa, Johannes Noé, Malgorzata Nowicka, Walter Bordogna, Peter N. Morcos, Vlatka Smoljanovic, Alice T. Shaw

Clinical TrialsKirk SmithFebruary 23, 2022Chemotherapy, targeted therapy, imaging, chest, lung cancer

Targeted Therapy for Older Patients with Non-Small Cell Lung Cancer: Systematic Review and Guidelines from the French Society of Geriatric Oncology...

Targeted therapy has become essential in the treatment of non-small cell lung cancer (NSCLC). There are currently no guidelines for older patients who are frailer with regard to this type of treatment. Two learned societies, the French Society of Geriatric Oncology (SoFOG) and the French-language Society of Pulmonology (SPLF)/French-language Oncology Group (GOLF), joined forces to conduct a systematic review of the literature from May 2010 to May 2021 regarding the efficacy, toxicity, and feasibility of targeted therapy in older patients with NSCLC. Guidelines were then drawn up to enable clinicians to adapt the type of targeted therapy proposed according to the oncological and geriatric profile of the older patient with NSCLC. READ ARTICLE

Cancers DOI:10.3390/cancers14030769

Authors: Greillier, L.; Gauvrit, M.; Paillaud, E.; Girard, N.; Montégut, C.;
Boulahssass, R.; Wislez, M.; Pamoukdjian, F.; Corre, R.;
Cabart, M.; et al.

ALK Inhibitors or Chemotherapy for Third Line in ALK-positive NSCLC? Real-world Data

We conducted a real-world multi-institutional analysis, aiming to compare the efficacy of third-line ALKi versus chemotherapy in these patients. Consecutive ALK-positive metastatic NSCLC patients treated with at least one ALKi were identified in the working databases of 7 Israeli oncology centers (the full cohort). Demographic and clinical data were collected. Patients receiving any systemic treatment beyond 2 ALKi comprised the third-line cohort, whether a third ALKi (group A) or chemotherapy (group B). Groups A and B were compared in terms of overall survival (OS) and time-to-next-treatment line (TNT). At a median follow-up of 41 months (95% confidence interval [CI]: 32-55), 80 (47.1%) have died. Median OS (mOS) in the full cohort (n = 170) was 52 months (95% CI: 32-65). Number of ALKi (hazard ratio [HR] 0.765; 95% CI: 0.61-0.95; P = .024) and age (HR 1.02, 95% CI: 1.01-1.04, P = .009) significantly associated with OS in the full cohort. The third-line cohort included 40 patients, of..... READ ARTICLE

The Oncologist DOI:10.1093/oncolo/oyab005

Authors: Moskovitz, Mor, Dudnik, Elizabeth, Shamai, Sivan, Rotenberg, Yakir, Popovich-Hadari, Noa, Wollner, Mira, Zer, Alona, Gottfried, Maya, Mishaeli, Moshe, Rosenberg, Shoshana Keren, Onn, Amir, Merimsky, Ofer, Urban, Damien, Peled, Nir, Maimon, Natalie, Bar, Jair

Post-chemotherapy and targeted therapy imaging of the chest in lung cancer

Non-small-cell lung cancer (NSCLC) is frequently diagnosed when it is not amenable to local therapies; therefore, systemic agents are the mainstay of therapy for many patients. In recent years, treatment of advanced NSCLC has evolved from a general approach primarily involving chemotherapy to a more personalised strategy in which biomarkers such as the presence of genomic tumour aberrations and the expression of immune proteins such as programmed death-ligand 1 (PD-L1), in combination with other elements of clinical information such as histology and clinical stage, guide management. For instance, pathways resulting in uncontrolled growth and proliferation of tumour cells due to epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements may be targeted by tyrosine kinase inhibitors (TKIs). In this article, we review the current state of medical oncology, imaging characteristics of mutations, pitfalls in response assessments and the imaging of complications. READ ARTICLE

Clinical Radiology DOI:10.1016/j.crad.2021.08.001

Authors: B. W. Carter, M. Altan, G. S. Shroff, M. T. Truong, I. Vlahos

EditorialKirk SmithJanuary 1, 2022Chemotherapy, targeted therapy, imaging, chest, lung cancer

Updates on Molecular Targeted Therapies for Intraparenchymal CNS Metastases

Central nervous system (CNS) metastases can occur in a high percentage of systemic cancer patients and is a major cause of morbidity and mortality in these patients. Almost any histology can find its way to the brain, but lung, breast, and melanoma are the most common pathologies seen in the CNS from metastatic disease. Identification of many key targets in the tumorigenesis pathway has been crucial to the development of a number of drugs that have demonstrated successful penetration of the blood–brain, blood–cerebrospinal fluid, and blood–tumor barriers. Targeted therapy and immunotherapy have dramatically revolutionized the field with treatment options that can provide successful and durable control of even CNS disease. In this review, we discuss major targets with successful treatment options as demonstrated in clinical trials. These include tyrosine kinase inhibitors, monoclonal antibodies, and antibody–drug conjugates. We also provide an update on the state of the field and highli..... READ ARTICLE

Cancers DOI:10.3390/cancers14010017

Authors: Akanksha Sharma, Lauren Singer, Priya Kumthekar

Safety and activity of alectinib plus bevacizumab in patients with advanced ALK-rearranged non-small-cell lung cancer: a phase I/II study

Alectinib, a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI), is highly effective in advanced ALK-rearranged non-small-cell lung cancer and represents a standard first-line therapy. New strategies are needed, however, to delay resistance. We conducted a phase I/II study to assess the safety and efficacy of combining alectinib with bevacizumab, a monoclonal antibody against vascular endothelial growth factor.
Patients with advanced ALK-rearranged non-squamous non-small-cell lung cancer were enrolled. The phase I portion employed a dose de-escalation strategy with alectinib and bevacizumab starting at the individual standard doses. The primary objective was to determine the recommended phase II dose (RP2D). In phase II, the primary objective was to evaluate the safety of the combination at the RP2D; the secondary objective was to determine extracranial and intracranial efficacy.
Eleven patients were enrolled between September 2015 and February 2020. Mos..... READ ARTICLE

ESMO Open, Cancer Horizons DOI:10.1016/j.esmoop.2021.100342

Authors: J.J. Lin, A. Muzikansky, E. Kennedy, I. Dagogo-Jack, A.T. Shaw, J.F. Gainor

Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-Analysis

In patients with NSCLC BMs and EGFR/ALK mutations, targeted TKIs improve intracranial and overall PFS compared to conventional modalities such as chemotherapy, with greater efficacy seen using newer generations of TKIs. This data is important for treatment selection and patient counseling, and highlights areas for future RCT research. READ ARTICLE

Frontiers in Oncology DOI:10.3389/fonc.2021.739765

Authors: Taslimi, S., Brar, K., Ellenbogen, Y., Deng, J., Hou, W., Moraes, F. Y., Glantz, M., Zacharia, B. E., Tan, A., Ahluwalia, M. S., Khasraw, M., Zadeh, G., & Mansouri, A.

Comparative Efficacy of Systemic Agents for Brain Metastases From Non-Small-Cell Lung Cancer With an EGFR Mutation/ALK Rearrangement: A Systematic Review and Network Meta-Analysis

Brain metastases (BM) from non-small-cell lung cancer (NSCLC) are frequent and carry significant morbidity, and current management options include varying local and systemic therapies. Here, we performed a systematic review and network meta-analysis to determine the ideal treatment regimen for NSCLC BMs with targetable EGFR-mutations/ALK-rearrangements.</sec><sec>MethodsWe searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published from inception until June 2020. Comparative RCTs including ≥10 patients were selected. We used a frequentist random-effects model for network meta-analysis (NMA) and assessed the certainty of evidence using the GRADE approach. Our primary outcome of interest was intracranial progression-free survival (iPFS).</sec><sec>ResultsWe included 24 studies representing 19 trials with 1623 total patients. Targeted tyrosine kinase inhibitors (TKIs) significantly improved iPFS, wit..... READ ARTICLE

Frontiers in Oncology DOI:10.3389/fonc.2021.739765

Authors: Taslimi Shervin, Brar Karanbir, Ellenbogen Yosef, Deng Jiawen, Hou Winston, Moraes Fabio Y., Glantz Michael, Zacharia Brad E., Tan Aaron, Ahluwalia Manmeet S., Khasraw Mustafa, Zadeh Gelareh, Mansouri Alireza

Three subtypes of lung cancer fibroblasts define distinct therapeutic paradigms

Cancer-associated fibroblasts (CAFs) are highly heterogeneous. With the lack of a comprehensive understanding of CAFs' functional distinctions, it remains unclear how cancer treatments could be personalized based on CAFs in a patient's tumor. We have established a living biobank of CAFs derived from biopsies of patients' non-small lung cancer (NSCLC) that encompasses a broad molecular spectrum of CAFs in clinical NSCLC. By functionally interrogating CAF heterogeneity using the same therapeutics received by patients, we identify three functional subtypes: (1) robustly protective of cancers and highly expressing HGF and FGF7; (2) moderately protective of cancers and highly expressing FGF7; and (3) those providing minimal protection. These functional differences among CAFs are governed by their intrinsic TGF-β signaling, which suppresses HGF and FGF7 expression. This CAF functional classification correlates with patients' clinical response to targeted therapies and also associates with th..... READ ARTICLE

Cancer Cell DOI:10.1016/j.ccell.2021.09.003

Authors: Hu H, Piotrowska Z, Hare PJ, Chen H, Mulvey HE, Mayfield A, Noeen S, Kattermann K, Greenberg M, Williams A, Riley AK, Wilson JJ, Mao YQ, Huang RP, Banwait MK, Ho J, Crowther GS, Hariri LP, Heist RS, Kodack DP, Pinello L, Shaw AT, Mino-Kenudson M, Hata AN, Sequist LV, Benes CH, Niederst MJ, Engelman JA.

Case Report: Identification of Two Rare Fusions, PDK1-ALK and STRN-ALK, That Coexist in a Lung Adenocarcinoma Patient and the Response to Alectinib

Several double ALK fusions coexisting in one patient have been reported. However, few studies have reported the clinical efficacy of ALK inhibitors in rare double ALK fusions. Here, we described a rare PDK1-ALK, STRN-ALK double-fusion variant in a patient with metastatic lung adenocarcinoma. The patient responded well to alectinib (600 mg) twice daily. This case shows a promising treatment option for patients with rare ALK double-fusion variants. READ ARTICLE

Frontiers in oncology DOI:10.3389/fonc.2021.722843

Authors: Zeng H, Li Y, Wang Y, Huang M, Zhang Y, Tian P, Li W.

Targeting EML4-ALK gene fusion variant 3 in thyroid cancer

Finding targetable gene fusions can expand the limited treatment options in radioactive iodine-refractory (RAI-r) thyroid cancer. To that end, we established a novel cell line ‘JVE404’ derived from an advanced RAI-r papillary thyroid cancer (PTC) patient, harboring an EML4-ALK gene fusion variant 3 (v3). Different EML4-ALK gene fusions can have different clinical repercussions. JVE404 cells were evaluated for cell viability and cell signaling in response to ALK inhibitors crizotinib, ceritinib and lorlatinib, in parallel to the patient’s treatment. He received, after first-line lenvatinib, crizotinib (Drug Rediscovery Protocol (DRUP) trial), and lorlatinib (compassionate use). In vitro treatment with crizotinib or ceritinib decreased viability in JVE404, but most potently and significantly only with lorlatinib. Western blot analysis showed a near total decrease of 99% and 89%, respectively, in pALK and pERK expression levels in JVE404 cells with lorlatinib, in contrast to remaining sig..... READ ARTICLE

Endocrine-Related Cancer DOI:10.1530/ERC-20-0436

Authors: Mehtap Derya Aydemirli, Jaap D H van Eendenburg, Tom van Wezel, Jan Oosting, Willem E Corver , Ellen Kapiteijn and Hans Morreau

Detecting Resistance to Therapeutic ALK Inhibitors in Tumor Tissue and Liquid Biopsy Markers: An Update to a Clinical Routine Practice

The survival of most patients with advanced stage non-small cell lung cancer is prolonged by several months when they are treated with first- and next-generation inhibitors targeting ALK rearrangements, but resistance inevitably emerges. Some of the mechanisms of resistance are sensitive to novel ALK inhibitors but after an initial tumor response, more or less long-term resistance sets in. Therefore, to adapt treatment it is necessary to repeat biological sampling over time to look for different mechanisms of resistance. To this aim it is essential to obtain liquid and/or tissue biopsies to detect therapeutic targets, in particular for the analysis of different genomic alterations. This review discusses the mechanisms of resistance to therapeutics targeting genomic alterations in ALK as well as the advantages and the limitations of liquid biopsies for their identification. READ ARTICLE

Cells DOI:10.3390/cells10010168

Authors: Paul Hofman

Review PaperKirk SmithJanuary 15, 2021liquid biopsy, lung cancer, ALK, resistance, targeted therapy

Neoadjuvant treatment of stage IIIA-N2 in EGFR-Mutant/ ALK-rearranged non-small cell lung cancer

Discusses risks and benefits of adjuvant therapy for treatment of earlier stage and locoregional lung cancer; advocates genome sequencing of earlier stage lung cancer. READ ARTICLE

Translational Lung Cancer Research DOI: 33569340

Authors: Reyes, Roxana, Reguart, Noemi

Real-World OutcomesKirk SmithJanuary 1, 2021Early stage, neoadjuvant therapy, targeted therapy, ALK, EGFR, NSCLC

How to select the best upfront therapy for metastatic disease? Focus on ALK-rearranged non-small cell lung cancer (NSCLC)

Since then, subsequent generations of ALK inhibitors have demonstrated superior efficacy and better CNS activity compared to crizotinib. Alectinib and brigatinib, both second-generation ALK inhibitors have been compared directly to crizotinib in the first-line setting and has demonstrated improved progression free survival (PFS) and intracranial response. Ceritinib, another second-generation ALK inhibitor has been shown to be superior to chemotherapy in ALK-rearranged disease with good CNS activity. Initial responses to ALK inhibitors are not always durable and resistance can occur as on-target or off-target alterations. Lorlatinib, a third-generation ALK inhibitor, has demonstrated activity in the treatment naïve setting and in resistance to crizotinib and second-generation ALK inhibitors. Lorlatinib has also shown improved PFS in patients harboring EML4-ALK variant 3, which is associated with the development of ALK resistance mutations, specifically G1202R. Another new ALK inhibitor, ensartinib, has demonstrated efficacy in the first-line setting and in alectinib refractory disease. READ ARTICLE

Translational Lung Cancer Research DOI: 10.21037/tlcr-20-331

Authors: Bing Xia, Misako Nagasaka, Viola W. Zhu, Sai-Hong Ignatius Ou, Ross A. Soo

Real-World OutcomesKirk SmithDecember 9, 2020NSCLC, ALK, TKI, targeted therapy

Outcome of Targeted Therapy Recommendations for Metastatic and Recurrent Head and Neck Cancers

Recurrent/metastatic (R/M) head and neck cancers bear a poor prognosis. In this analysis, we examined the efficacy and the outcome of targeted therapy recommendations based on the patients’ molecular tumor portrait after failure of all standard therapy options. In this single-center, real-world retrospective analysis of our platform for precision medicine, we analyzed the molecular profile of 50 patients diagnosed with R/M head and neck cancer. Tumor samples of the patients were examined using next-generation sequencing panels of mutation hotspots, microsatellite instability (MSI) testing, and immunohistochemistry (IHC). In 31 cases (62.0% of all patients), a molecular-driven targeted therapy approach was recommended. Eventually, 14 patients (28%) received the suggested targeted therapy. Six of fourteen patients (43%) achieved stable disease conditions and four patients (29%) experienced a progressive disease. The median time to treatment failure was 2.8 months. Therapy recommendations were significantly more often issued for men (p = 0.037) than for women. This analysis demonstrated that precision medicine provided the basis for molecular-driven therapy recommendations in over half of the patients with advanced therapy refractory head and neck cancers, with significantly more therapy recommendations for men. Our analysis showed that although precision medicine approaches are implementable and feasible for the management of recurrent/metastatic head and neck cancers in daily clinical routine, there are major limitations and challenges that have to be overcome. READ ARTICLE

Cancers DOI: 10.3390/cancers12113381

Authors: Hossein Taghizadeh, Robert M. Mader, Leonhard Müllauer, Thorsten Fuereder, Alexandra Kautzky-Willer and Gerald W. Prager

Optimal Timing And Technique Of Local Therapy For Brain Metastases From Non-Small Cell Lung Cancer With Driver Mutations

Objective(s): Brain metastases (BM) are frequent in non-small cell lung cancer patients with driver mutations (dm-NSCLC). Since the availability of brain-penetrating tyrosine kinase inhibitors (TKI), the role of local therapy (LT) for BM from dm-NSCLC is frequently discussed. This analysis examines prognostic factors, particularly the effect of LT timing and technique, in patients with BM from dm-NSCLC. Conclusion: In this analysis, early LT improved icPFS but not OS in TKI-naive patients with BM from dm-NSCLC, compared to upfront TKI treatment. No benefit was shown for WBRT over SRS regarding either icPFS or OS. In light of the toxicities of WBRT, the choice of RT technique should be considered carefully in the context of overall prognosis and quality of life. Especially patients presenting initially with multiple BM may benefit from delaying RT or from individualized approaches like the SRS of multiple or only selected BM instead of WBRT. READ ARTICLE

International Journal of Radiation Oncology DOI:10.1016/j.ijrobp.2020.07.096

Authors: R. El Shafie, T. Eichkorn, D. Weber, F. Bozorgmehr, L. König, S. Rieken, M. Thomas, J. Debus, P. Christopoulos

Outcomes Based On Brain Metastases Characteristics And Treatment Modality For Patients With EGFR-Mutated And ALK-Rearranged Non-Small Cell Lung Cancer (NSCLC)

Purpose/objective(s): Lung cancer patients with driver mutations and brain metastases can be managed with various modalities given intracranial penetrance of available tyrosine kinase inhibitors (TKIs). We sought to determine these patient’s outcomes based on brain metastases characteristics and the upfront treatment modalities utilized, including stereotactic radiosurgery (SRS) and whole brain radiation therapy (WBRT). Conclusion: For patients with EGFR-mutated or ALK-rearranged NSCLC and brain metastases, there was no difference in IC-PFS based on number or volume of brain metastases. Those treated with TKI alone experienced similar IC-PFS and risk of neurologic death as those also treated with radiotherapy. Further studies are needed to evaluate optimal treatment strategies for these patients, particularly for those with larger or symptomatic brain metastases when radiation is typically recommended. READ ARTICLE

International Journal of Radiation Oncology DOI:10.1016/j.ijrobp.2020.07.2048

Authors: S.W. Dutta, M.L. Mack, K.A. Ward, E. Aliotta, R. Hall, R.D. Gentzler, J.P. Sheehan

EML4-ALK, a potential therapeutic target that responds to alectinib in ovarian cancer

Ovarian cancer is prone to recurrence and chemotherapy resistance. Ovarian tumours of some patients have been positive for anaplastic lymphoma kinase fusion gene expression (ALK+). Preclinical studies indicate that anaplastic lymphoma kinase inhibitor can suppress the growth of ovarian cancer cells and transplantation tumours. Here, we present a patient with metastatic ALK+ high-grade serous ovarian cancer that testing positive for EML4-ALK (microtubule-associated protein-like 4 gene, fused to the anaplastic lymphoma kinase gene), experienced dramatic benefit after administration of the anaplastic lymphoma kinase inhibitor alectinib. This is the first clinical evidence that treatment with alectinib may provide a personalized maximum benefit for patients with high-grade serous ovarian cancer who are positive for EML4-ALK. READ ARTICLE

Japanese Journal of Clinical Oncology DOI:10.1093/jjco/hyaa156

Authors: Beina Hui, Jingping Zhang, Xiaobo Shi, Fangfang Xing, Yang W Shao, Yuanyuan Wang, Xiaozhi Zhang, Shuwen Wang

Responses to ALK Inhibitor Treatments in a Patient with Non-Small Cell Lung Cancer Harboring a Novel HPCAL1-ALK Fusion Variant: A Case Report

Anaplastic lymphoma kinase (ALK) fusion is present in approximately 2–7% of patients with lung adenocarcinoma. ALK fusion-positive patients can benefit from targeted therapy. We herein report a 53-year-old Chinese male patient diagnosed as lung adenocarcinoma with a smoking history. Next-generation sequencing was performed to detect somatic mutations of oncogenic drivers and tumor suppressor genes in plasma-derived circulating tumor DNA using an ultra-deep 160-gene panel. A novel HPCAL1-ALK fusion variant was identified in the patient responding to ALK inhibitor treatments, and the fusion variant was also confirmed by fluorescence in situ hybridization and immunohistochemical. Our study expands the mutational spectrum of ALK fusion variants and provides options for the precise treatment of such patients. READ ARTICLE

OncoTargets and therapy DOI:10.2147/OTT.S252210

Authors: Wang R, Qin J, Fan Y, Li Z, Chen C, Su W.

Patients with NSCLCs Harboring Internal Inversions or Deletion Rearrangements of the ALK Gene Have Durable Responses to ALK Kinase Inhibitors

Background

ALK fusions are targetable drivers in non-small-cell lung cancer (NSCLC). However, patients with NSCLC harboring ALK rearrangements without a fusion partner identified in DNA have also been shown to respond to ALK inhibitors. We aimed to characterize complex ALK variants that may predict sensitivity to multiple approved ALK inhibitors.

Methods

Comprehensive genomic profiling (CGP) of DNA isolated from formalin‐fixed paraffin‐embedded (FFPE) tumor tissue or blood-based circulating tumor DNA was performed for 39,159 NSCLC patients during routine clinical care. For a subset of cases, RNA sequencing was performed, and prior ALK test results and clinical treatment information were collected from treating physicians.

Results

We queried the Foundation Medicine NSCLC database and identified ALK internal inversions, as well as internal deletions, as the sole ALK rearrangements in 6 (0.02%) and 3 (0.01%) of cases, respectively. In cases with ALK internal inversions, RNA testing i..... READ ARTICLE

Lung Cancer: Targets and Therapy DOI:10.2147/LCTT.S239675

Authors: Schrock AB, Madison R, Rosenzweig M, Allen JM, Erlich RL, Wang SY, Chidiac T, Reddy VS, Riess JW, Yassa AE, Shakir A, Miller VA, Alexander BM, Venstrom J, McGregor K, Ali SM

Case StudyKirk SmithApril 17, 2020ALK rearrangement, inversion, deletion, genomic profiling, targeted therapy