Posts in Case Study
A case report of exceptional clinical response to chemoradiotherapy and tyrosine kinase inhibitors in a patient with EML4-ALK fusion variant 1 non-small cell lung cancer
A case report of exceptional clinical response to chemoradiotherapy and tyrosine kinase inhibitors in a patient with EML4-ALK fusion variant 1 non-small cell lung cancer

Herein, we report the case of a non-smoking 36-year-old female patient who was diagnosed with right lung adenocarcinoma in 2005 (cT1N3M0, IIIB) and received definitive chemoradiotherapy. The patient achieved a partial response, and her disease remained under control for 8 years. However, in May 2013, the patient was diagnosed with brain metastasis and underwent subsequent surgical resection, followed by postoperative brain radiotherapy and chemotherapy. Postoperative pathology confirmed ALK gene rearrangement, and next-generation sequencing performed in 2020 identified the EML4-ALK variant as variant 1. After progression-free survival lasting 4 years, new metastatic lesions were found in the patient’s right lung, and she was administered crizotinib for 20 months. Due to a suspicious recurrence in the intracranial surgical margin area, as well as an unbearable gastrointestinal reaction to crizotinib, alectinib was later adopted. At the 7-month follow-up, positron emission tomography/com..... READ ARTICLE

Translational Lung Cancer Research DOI: 10.21037/tlcr-20-1212

Authors: Xu X, Liu D, Wen J, Chen J, Fan M.

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Case StudyKirk SmithLung cancer, EML4-ALK, variant 1
Switching to an alternative ALK-inhibitor after alectinib-induced pneumonitis resulted in resolution of this adverse event
Switching to an alternative ALK-inhibitor after alectinib-induced pneumonitis resulted in resolution of this adverse event

This report adds to the available literature and demonstrates that utilizing an alternative ALK-inhibitor may be a potential management strategy for drug-induced ILD/pneumonitis that allows patients to continue to receive these effective therapies. READ ARTICLE

Current Problems in Cancer: Case Reports DOI: 10.1016/j.cpccr.2020.100023

Authors: Evan Bryson, Suresh Ramalingam, Tyler Beardslee

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Case StudyKirk SmithInterstitial lung disease, Pneumonitis, Drug-induced pneumonitis, ALK-inhibitor induced pneumonitis
Prolonged survival without progression under crizotinib treatment
Prolonged survival without progression under crizotinib treatment

In recent years, serious changes have been observed in the treatment algorithms of especially lung cancer patients. The start-up phase of treatment planning of metastatic lung adenocarcinoma patients is comprised of driver mutation research. Among the pretreatment options of patients diagnosed with EML4-ALK rearrangement, is crizotinib. The group disgnosed with EML4-ALK rearrangement, composes a little part of metastatic non-small cell lung cancer. In this case presented, I will focus on the start of crizotinib treatment and 53-month follow-up in remission in a patient, who has been operated twice and received cisplatin-based adjuvant chemotherapy twice, and relapsed for the second time as Stage-4. READ ARTICLE

Cancer Treatment and Research Communications DOI: 10.1016/j.ctarc.2020.100259

Author: Gulmez A Dr.

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Case StudyKirk SmithCrizotinib, EML4-ALK, Lung cancer
Clinicopathological features and immunohistochemical utility of NTRK-, ALK-, and ROS1-rearranged papillary thyroid carcinomas and anaplastic thyroid carcinomas
Clinicopathological features and immunohistochemical utility of NTRK-, ALK-, and ROS1-rearranged papillary thyroid carcinomas and anaplastic thyroid carcinomas

NTRK1/3, ALK, and ROS1 translocations have been reported in a minor subset of papillary thyroid carcinomas (PTCs). We aimed to elucidate the prevalence and clinicopathological characteristics of these gene rearrangements and the utility of immunohistochemistry (IHC) in PTC and anaplastic thyroid carcinoma (ATC). We screened nonradiation-exposed cases of 307 PTCs and 16 ATCs by IHC for pan-Trk, ALK, and ROS1, followed by fluorescence in situ hybridization (FISH). In the PTC group, IHC for pan-Trk, ALK, and ROS1 was positive in 18 cases (5.9%), 1 case (0.3%), and 12 cases (3.9%), respectively. Among the pan-Trk IHC–positive cases (n = 18), 2 cases (11.1%; 0.7% of all PTCs) had NTRK1 or NTRK3 gene rearrangement with conventional PTC histology. The ALK IHC–positive case (n = 1) was the follicular variant of PTC with consistent ALK gene rearrangement. ROS1 gene rearrangement was not detectable in the ROS1 IHC–positive PTCs (0/12) by FISH. Most (approximately 70%) of the pan-Trk or ROS1 IHC–..... READ ARTICLE

Human Pathology DOI:10.1016/j.humpath.2020.09.004

Authors: Yui Nozaki, Hidetaka Yamamoto, Takeshi Iwasaki, Masanobu Sato, Rina Jiromaru, Takahiro Hongo, Ryuji Yasumatsu, Yoshinao Oda

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Case StudyKirk SmithPapillary thyroid carcinoma, Anaplastic thyroid carcinoma, pan-Trk, NTRK, ALK, ROS1
Identification of novel bioactive molecules from garlic bulbs: A special effort to determine the anticancer potential against lung cancer with targeted drugs
Identification of novel bioactive molecules from garlic bulbs: A special effort to determine the anticancer potential against lung cancer with targeted drugs

... Garlic is used in the treatment of various ailments such as cancer, diabetes and cardiovascular diseases. The present study aims to explore the plausible mechanisms of the selected phytocompounds as potential inhibitors against the known drug targets of non-small-cell lung cancer (NSCLC)... The result of this study suggest that these identified phytocompounds from garlic would serve as promising leads for the development of lead molecules to design new multi-targeting drugs to address the different clinical forms of NSCLC. READ ARTICLE

Saudi Journal of Biological Sciences DOI:10.1016/j.sjbs.2020.09.041

Authors: R. Padmini, V. Uma Maheshwari, P.Saravanan, Keun Woo Lee, M. Razia, Mona S. Alwahibi, B. Ravindran, Mohamed Soliman Elshikh, Young Ock Kim, Hyungsuk Kim, Hak-Jae Kim

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Case StudyKirk SmithDocking, Garlic, Inhibitors, Lung cancer, Molecular dynamics simulations
ALK rearrangement in TFE3-positive renal cell carcinoma: Alternative diagnostic option to exclude Xp112 translocation carcinoma
ALK rearrangement in TFE3-positive renal cell carcinoma: Alternative diagnostic option to exclude Xp112 translocation carcinoma

Anaplastic lymphoma kinase (ALK)-rearranged renal cell carcinoma (RCC) is a rare subtype of RCC with gene fusion involving ALK at 2p23. It was first included in the renal tumor classification system by WorldHealth organization (WHO) as a distinct emerging/provisional renal entity in 2016. To date, only a few cases of ALK-RCC have been reported. Here, we report an exceptional case of ALK-RCC in a 15-year-old girl and review the literature. The patient presented with gross hematuria and a tumor measured 7 cm × 6 cm was found in the left kidney by imaging examination. Then a laparoscopic radical nephrectomy combined with local lymph node dissection was performed. The pathologic stage of the tumor was pT1bN1Mx and postoperative pathology showed that the tumor corresponded to WHO/ISUP grade 3–4. Immunohistochemistry (IHC) demonstrated moderate nuclear expression of TFE3 protein. Interestingly, ALK gene rearrangement rather than TFE3 gene rearrangement was observed by fluorescence in situ hy..... READ ARTICLE

Pathology - Research and Practice DOI:10.1016/j.prp.2020.153286

Authors: Yiqi Zhu, Ning Liu, Wei Guo, Xiaohong Pu, Hongqian Guo, Weidong Gan, Dongmei Li

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Case StudyKirk SmithRenal cell carcinoma, Translocation, FISH, ALK, HOOK1, TFE3
Successful treatment of de novo multiple primary malignancy with long term favorable outcome
Successful treatment of de novo multiple primary malignancy with long term favorable outcome

Multiple primary malignancies have been reported in anecdotal case reports and series in literature. The de novo occurrence poses diagnostic and therapeutic challenges. The co-occurrence of lung adenocarcinoma with acute myeloid leukemia synchronously has been reported in one small series in literature. There is limited data available regarding the treatment and response outcomes in such cases, where both malignancies are molecularly and therapeutically distinct. Hence, a comprehensive workup including a complete molecular profiling is necessary to render appropriate therapy to the patient. This report elucidates the same in a case of concurrent de novo lung adenocarcinoma and acute myeloid leukemia, where complete molecular workup culminated in a successful treatment outcome. READ ARTICLE

Current Problems in Cancer: Case Reports DOI:10.1016/j.cpccr.2020.100030

Authors: Ullas Batra, Shrinidhi Nathany, Anurag Mehta, Dinesh Bhurani, Mansi Sharma, Parveen Jain, NarenderTejwani

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Case StudyKirk SmithNon small cell lung carcinoma, Acute Myeloid Leukemia, Synchronous malignancy, India
Risk of thromboembolism in patients with ALK‐ and EGFR‐mutant lung cancer: A cohort study
Risk of thromboembolism in patients with ALK‐ and EGFR‐mutant lung cancer: A cohort study

Patients with ALK‐mutant advanced lung adenocarcinoma have the highest rate of TE. TE is associated with worse survival across molecular subtypes. These findings should be taken into consideration in decision‐making regarding thromboprophylaxis. READ ARTICLE

Journal of Thrombosis Haemostasis DOI: 10.1111/jth.15215

Authors: Roopkumar J., Poudel S.K., Gervaso L., Reddy C.A., Velcheti V., Pennell N.A., McCrae K.R., Khorana A.A.

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Case StudyKirk SmithALK, EGFR, molecular subtyping, NSCLC, thromboembolism
STRN-ALK, A Novel In-Frame Fusion With Response to Alectinib
STRN-ALK, A Novel In-Frame Fusion With Response to Alectinib

The ALK gene rearrangement is the second most common driver genomic alteration accounting for approximately 3% to 7% of patients with approved targeted therapies in NSCLC, after EGFR gene mutations. We here describe a rare case of a patient with STRN-ALK–rearranged NSCLC. READ ARTICLE

Journal of thoracic Oncology DOI: 10.1016/j.jtocrr.2020.100125

Authors: Misako Nagasaka, Nagaratna Sarvadevabatla, Shawn Iwata, Yubin Ge, Ammar Sukari, Christian Klosowski, Ronald Yanagihara

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Case StudyKirk SmithALK Fusion
Spindle cell tumor with CD34 and S100 co-expression and distinctive stromal and perivascular hyalinization showing EML4-ALK fusion
Spindle cell tumor with CD34 and S100 co-expression and distinctive stromal and perivascular hyalinization showing EML4-ALK fusion

Recently, a novel group of CD34+ and S100+ spindle cell tumors with distinctive stromal and perivascular hyalinization showing recurrent gene fusions involving RAF1, BRAF, NTRK1/2/3, and RET has been identified. ALK rearrangements have been rarely reported in this group of tumors. We report a 24-year-old woman with a 1.5-cm pink mass of the scalp. The tumor was made of spindle cells organized in fascicles or haphazardly arranged in a patternless architecture, with areas of stromal and perivascular hyalinization. The tumor cells diffusely expressed CD34 and S100, without SOX-10 expression. The tumor showed diffuse immunopositivity for ALK. RNA sequencing using next-generation sequencing (NGS) detected an EML4-ALK fusion. This case extends the spectrum of this newly described group of CD34+/S100+ spindle cell tumors at the molecular-genetic level. Dermatopathologists should be aware of this recent entity, as it may fall in the differential diagnosis of many other spindle cell tumors with..... READ ARTICLE

Journal of Cutaneous Pathology DOI:10.1111/cup.13926

Authors: Diane Abs, Samuel Landman, Amélie Osio, Pauline Lepesant, Pierre Schneider, Déborah Obadia, Philippe Moguelet, Cécile Farges, Brigitte Poirot, Jacqueline Lehmann-Che, Céleste Lebbé, Maxime Battistella

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Case StudyKirk SmithSpindle cell tumor, CD34 and S100 co-expression, stromal and perivascular hyalinization, EML4-ALK fusion
Long-term response to Crizotinib in a 17-year-old boy with naive alk-positive Non-Small Cell Lung Cancer
Long-term response to Crizotinib in a 17-year-old boy with naive alk-positive Non-Small Cell Lung Cancer

Lung cancer is the leading cause of cancer-related death. NSCLC accounts for 80-90% of cases. In younger patients, adenocarcinoma is the most frequent histotype and 3-7% expresses the rearrange-ment of ALK oncogene, sensitive to TKIs. Crizotinib is the first ALK inhibitor approved by FDA. We present the case of a 17-year-old male with metastatic naïve ALK-positive adenocarcinoma, treated with crizotinib. He received crizotinib and obtained a prolonged response with PFS of 33 months. Crizotinib can be extremely effective in adolescent with naïve ALK-positive NSCLC but it hardly penetrates blood-brain barrier. Resistance mechanisms will be investigated for a better man-agement. READ ARTICLE

Authorea DOI:10.22541/au.160620307.75734495/v1

Authors: megaro g, Miele E, Spinelli GP, et al.

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Case StudyKirk SmithADENOCARCINOMA, ADOLESCENCE, ALK, CRIZOTINIB. LUNG
Humanistic burden of living with anaplastic lymphoma kinase-positive non-small-cell lung cancer: findings from the ALKConnect patient insight network and research platform
Humanistic burden of living with anaplastic lymphoma kinase-positive non-small-cell lung cancer: findings from the ALKConnect patient insight network and research platform

ALKConnect demonstrated that disease progression, HRQoL, fatigue/sleep, ALK TKIs and employment matter in ALK+ NSCLC. READ ARTICLE

Lung Cancer Management DOI: 10.2217/lmt-2020-0018

Authors: Lin HM, Pan X, Biller A, J Covey K, Huang H, Sugarman R, Scipione F, West H.

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Case StudyKirk SmithctDNA, ALK, liquid biopsy, next-generation sequencing (NGS)
Spindle cell neoplasm with EML4-ALK gene fusion presenting as an intraosseous vertebral mass
Spindle cell neoplasm with EML4-ALK gene fusion presenting as an intraosseous vertebral mass

In this article, we describe a spindle cell neoplasm harboring an EML4-ALK gene fusion presenting as an intraosseous vertebral mass with extension into the adjacent soft tissue in a 65-year-old man. Histologically, the lesion was characterized by the presence of monotonous, cytologically bland spindle cells with loose myxoedematous stroma and interspersed areas of amianthoid-like collagen fiber deposition. Immunohistochemistry demonstrated strong diffuse staining for CD34 and S100, with absent immunoreactivity for SOX10. At 1 year of follow-up after resection, there is no evidence of local recurrence or metastatic disease. This case adds to the clinical and pathologic spectrum of the recently described group of kinase fusion-positive spindle cell neoplasms and represents the first reported intra-osseous example. The presence of ALK rearrangement in this lesion represents a potential therapeutic target, if clinically indicated. READ ARTICLE

Genes, Chromosomes & Cancer DOI:10.1002/gcc.22917

Authors: Jose G Mantilla, Hoiwan Cheung, Alice S Ha, Benjamin L Hoch, Yajuan J Liu, Robert W Ricciotti

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Case StudyKirk SmithEML4-ALK, gene fusion, sarcoma, soft tissue pathology
Omental Metastasis from ALK-positive Lung Cancer — A Case Report
Omental Metastasis from ALK-positive Lung Cancer — A Case Report

In conclusion, ALK-positive NSCLC with metastasis to the omentum is very rare. However, in patients with atypical symptoms like ascites, the possibility of a metastasis must be considered and repeat biopsy is always recommended. Targeted therapy in selected patients has shown a more durable response than chemotherapy. READ ARTICLE

The Egyptian Journal of Internal Medicine DOI:10.1186/s43162-020-00010-3

Authors: Khalid, T., Phelan, B., Yousif, A

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Case StudyKirk Smithomental metastasis, ALK, NSCLC
STRN-ALK Fusion in Lung Adenocarcinoma with Excellent Response Upon Alectinib Treatment: A Case Report and Literature Review
STRN-ALK Fusion in Lung Adenocarcinoma with Excellent Response Upon Alectinib Treatment: A Case Report and Literature Review

More than 90 fusion partners of ALK have been reported in NSCLC patients.
Striatin gene (STRN)-ALK fusion has rarely been reported. Case study of NSCLC patient harboring an STRN-ALK fusion and exhibiting an excellent response to alectinib treatment. READ ARTICLE

OncoTargets and Therapy DOI: 10.2147/OTT.S282933

Authors: Su C, Jiang Y, Jiang W, Wang H, Liu S, Shao Y, Zhao W, Ning R, Yu Q.

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Case StudyKirk Smithlung adenocarcinoma, STRN-ALK fusion, ctDNA, alectinib, targeted NGS
Remarkable Role of Chemotherapy in Selected ALK-Positive Non–Small-Cell Lung Cancer Before or After Targeted Therapy: Two Case Reports
Remarkable Role of Chemotherapy in Selected ALK-Positive Non–Small-Cell Lung Cancer Before or After Targeted Therapy: Two Case Reports

In both cases, conventional chemotherapy was proven lifesaving for the patients, which enabled them to receive subsequent-line targeted therapy and led to meaningful prolonged survival and an excellent quality of life that they continue to enjoy. The option of chemotherapy, even in this revolutionized era of precision medicine, should not be undermined. Chemotherapy continues to play a vital role in decreasing cancer burden and making this cancer salvageable in appropriately selected patients. READ ARTICLE

JCO Precision Oncology DOI: http://doi.org/10.1200/JCO.20.00505

Authors: Kunal Gawri, Richa Dawar, Kayla Haines, Mohammad Jahanzeb

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Case StudyKirk Smithchemotherapy, ALK
A case of late distant recurrence/metastasis (≧10 years after curative surgery) of anaplastic lymphoma kinase-rearranged lung cancer and the review of similar cases in the literature
A case of late distant recurrence/metastasis (≧10 years after curative surgery) of anaplastic lymphoma kinase-rearranged lung cancer and the review of similar cases in the literature

We experienced a 70-year-old female with brain and liver tumors. She underwent surgical operations for rectal cancer 8 year ago and lung cancer 16 years ago. Surgical removal of a brain tumor and a liver biopsy were performed. The brain tumor consisted of an adenocarcinoma with a solid signet-ring cell pattern. Under the possibility of metastatic anaplastic lymphoma kinase (ALK)-rearranged lung cancer in the brain and liver, immunohistochemistries (IHCs) for ALK were performed, returning positive results. Thus, metastasis of ALK-rearranged lung adenocarcinoma in the brain and liver had been confirmed. The patient was administered alectinib, which was well tolerated and has been in partial response for about one year and a half. By the genetic analyses for EML4-ALK variants, both the previous lung cancer and metastatic brain tumor were shown to harbor the same EML4-ALK variant 3 fusion. We thus concluded that ALK-rearranged lung adenocarcinoma has recurred as liver and brain metastases ..... READ ARTICLE

Human Pathology: Case Reports DOI:10.1016/j.ehpc.2020.200421

Authors: Shohei Matsuo, Yoshitane Tsukamoto, Eiichiro Mabuchi, Shunichi Negoro, Seiichi Hirota

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Case StudyKirk SmithLung cancer, Late recurrence/metastasis, EML-ALK fusion
Effects of ALK inhibitors (PF-02341066 and PF-06463922) with radiotherapy in EML4 – ALK fusion positive (H2228 and 185IG) and negative (A549) experimental lung cancer cell lines
Effects of ALK inhibitors (PF-02341066 and PF-06463922) with radiotherapy in EML4 – ALK fusion positive (H2228 and 185IG) and negative (A549) experimental lung cancer cell lines

Purpose/Objective(s): The management of non-small cell lung cancer (NSCLC) patients with chromosomal rearrangements of the anaplastic lymphoma kinase gene (ALK) is challenging. Indeed, the efficacy of the tyrosine kinase inhibitor (TKI) of novel generation may discuss the place of combined treatment with radiotherapy. We aimed to investigate the effects of combined radiotherapy and PF-02341066 or PF-06463922 in A549 and 185IG or H2228 cell lines, the former is a wild type ALK NSCLC model and the two latter are ALK-positive NSCLC models... Conclusion: In the current study, PF-02341066 induced notably cell cycle arrest at G2/M phase and PF-06463922 induced G1 arrest, in H2228 cells. Also, results suggest that the administration of PF-02341066 and PF-06463922 after irradiation could increase the induction of DNA damages due to IR in a panel of 3 NSCLC cell lines, compared to IR first followed by TKI treatment. These results could influence the clinical combination strategy for EML4 – ALK..... READ ARTICLE

International Journal of Radiation Oncology*Biology*Physics DOI:10.1016/j.ijrobp.2020.07.1599

Authors: D.N. Antoni, H. Burckel, G. Noel

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Case StudyKirk SmithALK inhibitors, PF-02341066, PF-06463922, radiotherapy, EML4 – ALK fusion, positive H2228 and 185IG, negative A549, experimental lung cancer cell lines
Lorlatinib and Bevacizumab Activity in ALK- Rearranged Lung Cancers After Lorlatinib Progression
Lorlatinib and Bevacizumab Activity in ALK- Rearranged Lung Cancers After Lorlatinib Progression

In conclusion, the combination of lorlatinib and bevacizumab demonstrated activity and was safe in patients with heavily pretreated, ALK-rearranged lung cancers that had progressed on single-agent lorlatinib immediately before the combination. These findings add to a growing body of literature on the potential utility of antiangiogenic therapy with TKI therapy in oncogene-driven cancers. READ ARTICLE

JCO Precision Oncology DOI: 10.1200/PO.20.00271

Authors: Choudhury NJ, Young RJ, Sellitti M, Miller A, Drilon A.

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Case StudyKirk Smithlorlatinib, bevacizumab
Novel Resistance Mechanisms Including L1196Q, P1094H, and R1248_D1249 Insertion in Three Patients With NSCLC After ALK Tyrosine Kinase Inhibitor Treatment
Novel Resistance Mechanisms Including L1196Q, P1094H, and R1248_D1249 Insertion in Three Patients With NSCLC After ALK Tyrosine Kinase Inhibitor Treatment

"Nine patients had no known ALK resistance mechanisms. Four had ALK amplification. L1196M, I1171N, and G1269A, mutations that are known to indicate resistance to ALK TKIs, were detected in one patient each. Small cell carcinoma and sarcomatoid transition were found in one case each. L1196Q, P1094H, and exon 24 76-base pair insertion were detected after the second-generation ALK TKIs.The combination of a genetic analysis and a computational simulation model may make a prediction of resistance mechanisms for overcoming ALK TKI resistance, and the construction of a genomic and simulation fused database is important for the development of personalized medicine in this field." READ ARTICLE

Journal of Thoracic Oncology DOI: 10.1016/j.jtho.2020.09.023

Authors: Furuta H, Araki M, Masago K, Sagae Y, Fujita S, Seto K, Shimizu J, Horio Y, Sasaki E, Hosoda W, Katayama R, Okuno Y, Hida T.

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Case StudyKirk SmithAcquired resistance, ALK, MD simulation, non-small cell lung cancer (NSCLC)