Deep RNA Sequencing Revealed Fusion Junctional Heterogeneity May Predict Crizotinib Treatment Efficacy in ALK-Rearranged NSCLC

Gene fusion variants in ALK-rearranged NSCLC may predict patient outcomes, but previous results have been inconclusive. Fusion isoforms coexisting in the same tumor may affect the efficacy of targeted therapy, but they have not been investigated.
Patients with ALK-rearranged NSCLC who received crizotinib treatments were recruited. Precrizotinib tumor tissues were analyzed by the anchored multiplex polymerase chain reaction for targeted RNA sequencing. Kaplan-Meier and Cox regression were used to compare overall and progression-free survivals.
It was concluded that intratumoral EML4-ALK isoforms may predict the efficacy of targeted therapy in ALK-rearranged NSCLC. Temporal changes of intratumoral fusion isoforms may result from differential selection pressures that a drug might have on one isoform over another. Larger studies on fusion heterogeneity using RNA sequencing are warranted. READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.09.016

Authors: Zhengbo Song, Shifeng Lian, Silvia Mak, Maggie Zi-Ying Chow, Chunwei Xu, Wenxian Wang, Hoi Yee Keung, Chenyu Lu, Firaol Tamiru Kebede, Yanqiu Gao, Wah Cheuk, William Chi Shing Cho, Mengsu Yang, Zongli Zheng

Predictive role of neutropenia under crizotinib treatment in ALK-rearranged nonsmall cell lung cancer patients: A single-institution retrospective analysis

Anaplastic lymphoma kinase (ALK)-rearranged nonsmall cell lung cancer (NSCLC) represents a molecular subgroup with high sensitivity to ALK inhibitors. Tyrosine kinase inhibitor crizotinib, an anticancer drug acting as an ALK inhibitor, has shown remarkable response in ALK-positive NSCLC. The aim of our study is to explore the adverse events (AEs) of patients on crizotinib therapy and analyze the predictability of AEs for better survival or response on NSCLC patients. We find that neutropenia under crizotinib treatment was found to be associated with improved PFS suggesting that neutropenia might be an important determinant in treatment and survival strategies. READ ARTICLE

Indian Journal of Cancer DOI:10.4103/ijc.IJC_71_20

Authors: Pınar Gürsoy, Burcu Çakar, Deniz Nart, Erdem Göker

Real-World OutcomesKirk SmithSeptember 30, 2021ALK, NSCLC, crizotinib, AE, neutropenia, PFS

Does Pemetrexed Work in Targetable, Nonsquamous Non-Small-Cell Lung Cancer? A Narrative Review

Pemetrexed is currently mainly considered for the treatment of advanced nonsquamous non-small-cell lung cancer (NSCLC) negative for gene mutations/rearrangements (wild-type disease (WTD)). This narrative review aimed to highlight the role of pemetrexed in the treatment of onco-driven nonsquamous advanced NSCLC by reviewing published clinical studies. For epidermal growth factor receptor (EGFR) mutations, patient survival following first-line pemetrexed–platinum was longer than for WTD. Later-line pemetrexed-based treatment after tyrosine kinase inhibitor (TKI) failure provided greater benefits than non-pemetrexed regimens. First- and later-line pemetrexed-based therapy also provided survival benefits in patients with anaplastic lymphoma kinase (ALK) or ROS proto-oncogene 1 (ROS1) rearrangements. In patients with rearranged during transfection (RET) proto-oncogene rearrangements, survival with pemetrexed was similar to that in ALK- and ROS1-positive patients and longer than that in pati..... READ ARTICLE

Cancers DOI:10.3390/cancers12092658

Authors: Jin-Yuan Shih, Akira Inoue, Rebecca Cheng, Rocio Varea, Sang-We Kim

Pathological cytomorphologic features and the percentage of ALK FISH-positive cells predict pulmonary adenocarcinoma prognosis: a prospective cohort study

We conducted a study to explore the relationship between pathological cytomorphologic features and the percentage of anaplastic lymphoma kinase (ALK)-positive cells to better predict pulmonary adenocarcinoma prognosis with crizotinib treatment.
We investigated 60 cases of patients with ALK-positive advanced or metastatic non-small cell lung cancer (NSCLC). Immunohistochemistry was performed to screen for ALK rearrangement. Fluorescence in situ hybridization (FISH) was used to detect the percentage of ALK-positive cells. The primary objectives of the study were the progression-free survival (PFS), the 3-year overall survival, and the 3-year overall survival (OS) rates. The secondary objectives of the study were the disease control rate (DCR) and the overall response rate (ORR).
We concluded that signet ring cell cytomorphologic characteristics of pulmonary adenocarcinoma are associated with the percentage of ALK-positive cells. Signet ring cell cytomorphologic characteristics and the percentage of ALK-positive cells might predict the prognosis of pulmonary adenocarcinoma with crizotinib treatment. READ ARTICLE

World Journal of Surgical Oncology DOI:10.1186/s12957-021-02386-0

Authors: Fenge Jiang, Congcong Wang, Ping Yang, Ping Sun, Jiannan Liu

ALK inhibitor-induced bradycardia: A systematic-review and meta-analysis

Anaplastic Lymphoma Kinase (ALK) inhibitors have revolutionized the treatment of advanced ALK-positive non-small cell lung cancer (NSCLC), improving progression-free survival. Bradycardia is a potential adverse effect of these agents. We aimed to determine the risk of bradycardia associated with ALK inhibitors in patients with advanced NSCLC.We find that crizotinib for the treatment of NSCLC is associated with a higher risk for bradycardia compared to standard chemotherapy. There is no evidence of a difference in bradycardia risk between crizotinib and newer ALK inhibitors. READ ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2021.08.014

Authors: Filipe Cirne, Shijie Zhou, Coralea Kappel, Adam El-Kadi, Carly C. Barron, Peter M. Ellis, Stephanie Sanger, Darryl P. Leong

Brain Metastases in EGFR- and ALK-Positive NSCLC: Outcomes of Central Nervous System-Penetrant Tyrosine Kinase Inhibitors Alone Versus in Combination With Radiation

Management of central nervous system (CNS) metastases in patients with driver-mutated NSCLC has traditionally incorporated both tyrosine kinase inhibitors (TKIs) and intracranial radiation. Whether next generation, CNS-penetrant TKIs can be used alone without upfront radiation, however, remains unknown. This multi-institutional retrospective analysis aimed to compare outcomes in patients with EGFR- or ALK-positive NSCLC who received CNS-penetrant TKI therapy alone versus in combination with radiation for new or progressing intracranial metastases. A total of 147 patients were included (EGFR n = 94, ALK n = 52, both n = 1). In patients receiving radiation, larger metastases, neurologic symptoms, and receipt of steroids were more common. There were no significant differences between TKI and CNS radiation therapy plus TKI groups for any of the study outcomes, including time to progression (8.5 versus 6.9 mo, p = 0.13 [EFGR] and 11.4 versus 13.4 mo, p = 0.98 [ALK]), time to intracranial pr..... READ ARTICLE

Journal of Thoracic Oncology DOI:10.1016/j.jtho.2021.08.009

Authors: Nicholas J.Thomas, Nathaniel J. Myall, Fangdi Sun, Tejas Patil, Rao Mushtaq, Chandler Yu, Sumi Sinha, Erqi L. Pollom, Seema Nagpal. Ross Camidge, Chad G. Rusthoven, Steve E. Braunstein, Heather A. Wakelee and Caroline E. McCoach

ALK Gene Rearrangements in Lung Adenocarcinomas: Concordance of Immunohistochemistry, Fluorescence In Situ Hybridization, RNA In Situ Hybridization, and RNA Next-Generation Sequencing Testing

The 2018 updated molecular testing guidelines for patients with advanced lung cancer incorporated ALK immunohistochemistry (IHC) analysis as an equivalent to fluorescence in situ hybridization (FISH) method recommended in 2013. Nevertheless, no specific recommendation for alternative methods was proposed owing to insufficient data. The aim of this study was to compare the results of ALK IHC, FISH, RNA next-generation sequencing (NGS), and RNA in situ hybridization (ISH) with available clinical data. Our results reveal high concordance among IHC, RNA NGS, and RNA ISH. In cases of discordance with available RNA NGS, FISH result was positive whereas IHC and ISH results were negative. On the basis of our data, multimodality testing is recommended to identify discrepant results and patients (un)likely to respond to tyrosine kinase inhibitors. READ ARTICLE

JTO Clinical and Research Reports DOI:0.1016/j.jtocrr.2021.100223

Authors: Carleigh R. Canterbury, Helen Fernandes, John P. Crapanzano, Vundavalli V. Murty, Mahesh M.Mansukhani, Catherine A. Shu, Matthias Szabolcs, Anjali Saqi

Comparison of solid tissue sequencing and liquid biopsy accuracy in identification of clinically relevant gene mutations and rearrangements in lung adenocarcinomas

Screening for therapeutic targets is standard of care in the management of advanced non-small cell lung cancer. However, most molecular assays utilize tumor tissue, which may not always be available. “Liquid biopsies” are plasma-based next generation sequencing (NGS) assays that use circulating tumor DNA to identify relevant targets. To compare the sensitivity, specificity, and accuracy of a plasma-based NGS assay to solid-tumor-based NGS we retrospectively analyzed sequencing results of 100 sequential patients with lung adenocarcinoma at our institution who had received concurrent testing with both a solid-tissue-based NGS assay and a commercially available plasma-based NGS assay. Patients represented both new diagnoses (79%) and disease progression on treatment (21%); the majority (83%) had stage IV disease. Tissue-NGS identified 74 clinically relevant mutations, including 52 therapeutic targets, a sensitivity of 94.8%, while plasma-NGS identified 41 clinically relevant mutations, a ..... READ ARTICLE

Modern Pathology DOI:10.1038/s41379-021-00880-0

Authors: Lawrence Hsu Lin, Douglas H. R. Allison, Yang Feng, George Jour, Kyung Park, Fang Zhou, Andre L. Moreira, Guomiao Shen, Xiaojun Feng, Joshua Sabari, Vamsidhar Velcheti, Matija Snuderl, Paolo Cotzia

Association between circulating tumor DNA burden and disease burden in patients with ALK-positive lung cancer

Plasma genotyping is an emerging approach for the identification of genetic alterations mediating resistance to ana-plastic lymphoma kinase (ALK)–targeted therapy. The authors reviewed plasma genotyping and imaging findings to assess the correla-tion between circulating tumor DNA (ctDNA) burden and disease burden in patients with ALK-positive lung cancer. The authors analyzed 97 plasma specimens from 75 patients with ALK-positive lung cancer to identify ALK and non-ALK alterations. In patients with ALK-positive lung cancer, the maximum plasma alteration AF and maximum ALK alteration AF correlate with the extrathoracic burden of disease and are more predictive of tumor burden com-pared with the ALK fusion AF alone. READ ARTICLE

Cancer DOI:10.1002/cncr.33118

Authors: Eric W. Zhang , Ibiayi Dagogo-Jack MD, Anderson Kuo MD, PhD, Marguerite M. Rooney BSc, Alice T. Shaw MD, PhD, Subba R. Digumarthy MD

Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study

Background: Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use. Methods: This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 ( n = 5), 1 ( n = 26) or none ( n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program. Results: Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)). Median progression free survival (PFS) was estimated to be 21.8 months, and median overall survival (OS) approached to 70.1 months. Only 4 out of 35 patients experienced no adverse effects; two of them were the only subjects who had no clinical benefit from lorlatinib. PFS and OS in the no-adverse-events lorlatinib users were strikingly lower as compared..... READ ARTICLE

Translational Oncology DOI:10.1016/j.tranon.2021.101121

Authors: Sergey V. Orlov, Aglaya G. Iyevleva, Elena A. Filippova, Alexandra M. Lozhkina, Svetlana V. Odintsova, Tatiana N. Sokolova, Natalia V. Mitiushkina, Vladislav I. Tiurin, Elena V. Preobrazhenskaya, Alexandr A. Romanko, Alexandr S. Martianov, Alexandr O. Ivantsov, Svetlana N. Aleksakhina, Alexandr V. Togo, Evgeny N. Imyanitov.

Local Consolidative Therapy Vs. Maintenance Therapy or Observation for Patients With Oligometastatic Non-Small-Cell Lung Cancer: Long-Term Results of a Multi-Institutional, Phase II, Randomized Study

Our previously published findings reported that local consolidative therapy (LCT) with radiotherapy or surgery improved progression-free survival (PFS) and delayed new disease in patients with oligometastatic non–small-cell lung cancer (NSCLC) that did not progress after front-line systemic therapy. Herein, we present the longer-term overall survival (OS) results accompanied by additional secondary end points. In patients with oligometastatic NSCLC that did not progress after front-line systemic therapy, LCT prolonged PFS and OS relative to MT/O. READ ARTICLE

Journal of Clinical Oncology DOI: 10.1200/JCO.19.00201

Authors: Daniel R. Gomez, Chad Tang, Jianjun Zhang, George R. Blumenschein Jr, Mike Hernandez, J. Jack Lee, Rong Ye, David A. Palma, Alexander V. Louie, D. Ross Camidge, Robert C. Doebele, Ferdinandos Skoulidis, Laurie E. Gaspar, James W. Welsh, Don L. Gibbons, Jose A. Karam, Brian D. Kavanagh, Anne S. Tsao, Boris Sepesi, Stephen G. Swisher, John V. Heymach

Real-World OutcomesKirk SmithJuly 25, 2021ALK, tau, Alzheimer's disease (AD)

Comparative Efficacy and Safety of Lorlatinib and Alectinib for ALK-Rearrangement Positive Advanced Non-Small Cell Lung Cancer in Asian and Non-Asian Patients

The treatment of anaplastic lymphoma kinase (ALK) rearrangement-positive (ALK-p) advanced non-small cell lung cancer (NSCLC) remains a challenge. We compared the safety and efficacy of lorlatinib and alectinib in patients with ALK-p ALK-inhibitor‒naïve advanced NSCLC (in overall participants and in the Asian and non-Asian subgroups). The results showed that in the overall participant group, the efficacy of lorlatinib and alectinib was not significantly different in terms of progression-free survival (PFS) and overall survival (OS). Although in the Asian subgroup, PFS was not significantly different upon treatment with lorlatinib or alectinib, in the non-Asian subgroup, PFS was significantly better in response to lorlatinib than with alectinib. Grade 3 or higher adverse events in the overall participant group were significantly more frequent with lorlatinib than with alectinib. These results will provide valuable information that would enable the improvement of treatment strategies for ALK-p ALK-inhibitor‒naïve advanced NSCLC. READ ARTICLE

Cancers DOI:10.3390/cancers13153704

Authors: Koichi Ando, Ryo Manabe,Yasunari Kishino, Sojiro Kusumoto,Toshimitsu Yamaoka, Akihiko Tanaka, Tohru Ohmori and Hironori Sagara

Real-World Outcomes, group4Kirk SmithJuly 23, 2021alectinib, ALK rearrangement, lorlatinib

Real-world insights into patients with advanced NSCLC and MET alterations

Heterogeneous treatments reflect the changing landscape and availability of new treatments, as well as the high unmet medical need in older, METex14 patients who had more advanced disease at diagnosis. MET-targeted therapies could be beneficial in patients with these rare MET alterations. RE AD ARTICLE

Lung Cancer DOI:10.1016/j.lungcan.2021.06.015

Authors: Marisa Bittonia James Chih-Hsin Yang, Jin-Yuan Shih, Nir Peled, Egbert F. Smite, D. Ross Camidge, Rajeswara Rao Arasada, Dina Okseng, Emmanuelle Boutmy, Christopher Stroh, Andreas Johne, David P. Carbonea and Paul K. Paik

Comparison of Clinical Efficacy of Alectinib Versus Crizotinib in ALK-Positive Non-Small Cell Lung Cancer: A Meta-Analysis

Alectinib in terms of overall response rate, progression-free survival and partial response is superior to crizotinib in the treatment of ALK-positive non-small cell lung cancer and is well tolerated. Compared with crizotinib, alectinib is more effective than crizotinib and has a lower incidence of total adverse reactions. Meta-analysis results confirm the strong base for alectinib as a first-line treatment for ALK-positive NSCLC. READ ARTICLE

Frontiers in Oncology DOI: 10.3389/fonc.2021.646526

Authors: Hao Tang, Longyu Jin, Zhang Zhang, Zhibin Jiang and Zeeshan Malik

Real-World Outcomes, group5Kirk SmithJune 3, 2021alectinib, crizotinib, ALK+, NSCLC

Impact of ALK Inhibitors in Patients With ALK-Rearranged Nonlung Solid Tumors

We identified seven patients (inflammatory myofibroblastic tumors, n = 3; ALK-positive histiocytosis, n = 1; histiocytic sarcoma, n = 1; osteosarcoma, n = 1; and parotid adenocarcinoma, n = 1), with a median age of 17 years. Two rare ALK fusions, namely, CTNNA1-ALK and ITSN2-ALK, were identified. As initial ALK-TKI therapy, five patients received alectinib and two received crizotinib. The objective response rate for the initial ALK-TKI therapy was 85.7% (95% CI, 44 to 97), including two patients who received alectinib and achieved complete response. The median progression-free survival was 8.1 months (range, 1.7 to not estimable). There were no treatment interruptions or dose reductions because of adverse events caused by alectinib. This study highlights the potential benefit of ALK-TKIs, especially alectinib, in patients with ALK-rearranged nonlung solid tumors. READ ARTICLE

Journal of Thoracic Oncology DOI: 10.1200/PO.20.00383 JCO

Authors: Yuki Takeyasu, Hitomi S. Okuma, Yuki Kojima, Tadaaki Nishikawa, Maki Tanioka, Kazuki Sudo, Tatsunori Shimoi, Emi Noguchi, Ayumu Arakawa, Taisuke Mori, Kuniko Sunami, Takashi Kubo, Takashi Kohno, Yoshida Akihiko, Noboru Yamamoto and Kan Yonemori

Characteristics of central nervous system progression in non-small cell lung cancer treated with crizotinib or alectinib

Aims: We compared the clinical-radiographic characteristics of CNS metastases among patients undergoing crizotinib and alectinib treatment for ALK-positive NSCLCs. Conclusion: We observed no significant difference in the clinical-radiographic characteristics of CNS progression between patients undergoing crizotinib and alectinib treatments. Local therapy, including stereotactic radiosurgery, for CNS progression may be suitable and important following alectinib and crizotinib treatment. READ ARTICLE

Cancer Reports DOI:doi.org/10.1002/cnr2.1414

Authors: Hiroaki Sakamoto, Noriko Yanagitani, Ryo Manabe, Ryosuke Tsugitomi, Shinsuke Ogusu, Takehiro Tozuka, Hiroshi Yoshida, Yoshiaki Amino, Ryo Ariyasu, Ken Uchibori, Satoru Kitazono, Sadatomo Tasaka, Makoto Nishio

Impact of ALK Inhibitors in Patients With ALK-Rearranged Non lung Solid Tumors

We identified seven patients (inflammatory myofibroblastic tumors, n = 3; ALK-positive histiocytosis, n = 1; histiocytic sarcoma, n = 1; osteosarcoma, n = 1; and parotid adenocarcinoma, n = 1), with a median age of 17 years. Two rare ALK fusions, namely, CTNNA1-ALK and ITSN2-ALK, were identified. As initial ALK-TKI therapy, five patients received alectinib and two received crizotinib. The objective response rate for the initial ALK-TKI therapy was 85.7% (95% CI, 44 to 97), including two patients who received alectinib and achieved complete response. The median progression-free survival was 8.1 months (range, 1.7 to not estimable). There were no treatment interruptions or dose reductions because of adverse events caused by alectinib. This study highlights the potential benefit of ALK-TKIs, especially alectinib, in patients with ALK-rearranged nonlung solid tumors.

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Journal of Clinical Oncology: Precision Oncology DOI:10.1200/PO.20.00383

Authors: Yuki
Takeyasu; Hitomi S. Okuma; Yuki Kojima; Tadaaki Nishikawa; Maki Tanioka; Kazuki Sudo; Tatsunori Shimoi; Emi Noguchi; Ayumu Arakawa; Taisuke Mori; Kuniko Sunami, Takashi Kubo; Takashi Kohno; Yoshida Akihiko; Noboru Yamamoto; and Kan Yonemori

Real-World OutcomesKirk SmithMay 3, 2021CTNNA1-ALK, ITSN2-ALK, alternative ALKfusion, TKI

Significance of TP53 Mutation in Cellular Process and Disease Progression in Lung Adenocarcinoma

Analysis of the TCGA data showed TP53 mutations in 22% of LUAD patients. Clinicopathological analyses demonstrated that TP53 mutation was correlated with the disease progression but not prognosis. We identified 1935 differentially expressed genes (DEGs). Functional enrichment analysis showed that the DEGs were mainly concentrated in metabolism, cell differentiation, and cancer-related pathways. The top hub genes were identified and disease analysis revealed the most critical genes related to disease progression and prognosis. The expression levels of several of these genes were then tested in tumor tissues. Our results showed that TP53 mutation plays a critical role in cellular process and the clinicopathological findings in LUAD. We also identified potential key genes, which could provide novel evidence for individualized treatment. READ ARTICLE

Genetic Testing and Molecular Biomarkers DOI:10.1089/gtmb.2020.0304

Authors: Yongbo Hou, Sheng Tan, Guoxiang Wang

Real-World OutcomesKirk SmithMay 1, 2021TP53, adenocarcinoma, lung

Spectrum of Mechanisms of Resistance to Crizotinib and Lorlatinib in ROS1 Fusion–Positive Lung Cancer

We performed molecular profiling of the largest series to date of crizotinib- and lorlatinib-resistant biopsies, finding that ROS1 kinase domain mutations mediate resistance in one third to one half of cases, respectively. Recurrent resistance mutations in ROS1 included G2032R and less well-characterized L2086F. In Ba/F3 models, type I inhibitors, including crizotinib, entrectinib, and lorlatinib, were unable to overcome ROS1L2086F, whereas type II inhibitor, cabozantinib, maintained potency. We additionally detected MET and RAS-MAPK alterations in resistant specimens. Our study highlights the importance of developing novel ROS1 inhibitors with potency against recurrent ROS1 resistance mutations and may inform sequential treatment strategies in ROS1+ lung cancer. ROS1 mutations mediate resistance to crizotinib and lorlatinib in more than one third of cases, underscoring the importance of developing next-generation ROS1 inhibitors with potency against these mutations, including G2032R and L2086F. Continued efforts are needed to elucidate ROS1-independent resistance mechanisms. READ ARTICLE

Cancer Mechanisms and Therapy DOI:10.1158/1078-0432.CCR-21-0032

Authors: Jessica J. Lin, Noura J. Choudhury, Satoshi Yoda, Viola W. Zhu, Ted W. Johnson, Ramin Sakhtemani, Ibiayi Dagogo-Jack, Subba R. Digumarthy, Charlotte Lee, Andrew Do, Jennifer Peterson, Kylie Prutisto-Chang, Wafa Malik, Harper G. Hubbeling, Adam Langenbucher, Adam J. Schoenfeld, Christina J. Falcon, Jennifer S. Temel, Lecia V. Sequist, Beow Y. Yeap, Jochen K. Lennerz, Alice T. Shaw, Michael S. Lawrence, Sai-Hong Ignatius Ou, Aaron N. Hata, Alexander Drilon, Justin F. Gainor

Real-World OutcomesKirk SmithMay 1, 2021crizotinib, lorlatinib, ROS1

Earlier extracranial progression and shorter survival in ALK-rearranged lung cancer with positive liquid rebiopsies

Background: Liquid rebiopsies can detect resistance mutations to guide therapy of anaplastic lymphoma kinase-rearranged (ALK+) non-small-cell lung cancer (NSCLC) failing tyrosine kinase inhibitors (TKI). Here, we analyze how their results relate to the anatomical pattern of disease progression and patient outcome. Conclusions: Positive blood-based liquid rebiopsies in ALK+ NSCLC characterize biologically more aggressive disease and are common with extracranial, but rare with CNS-only progression or benign radiologic changes. These results reconcile the increased detection of ALK resistance mutations with other features of the high-risk EML4-ALK V3-associated phenotype. Conversely, most oligoprogressive patients with negative liquid biopsies have a more indolent course without need for early change of systemic treatment. READ ARTICLE

Transl Lung Cancer Research DOI:10.21037/tlcr-21-32

Authors: Petros Christopoulos, Steffen Dietz, Arlou K. Angeles, Stephan Rheinheimer, Daniel Kazdal, Anna-Lena Volckmar, Florian Janke, Volker Endris, Michael Meister, Mark Kriegsmann, Thomasz Zemojtel, Martin Reck, Albrecht Stenzinger, Michael Thomas, Holger Sültmann