Publications by authors named "Myung-Ju Ahn"

402 Publications

Long-Term Survival in Non-Small Cell Lung Cancer Patients with Metachronous Brain-Only Oligorecurrence Who Underwent Definitive Treatment.

Cancer Res Treat 2021 May 6. Epub 2021 May 6.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: Metachronous brain-only oligorecurrence in patients with non-small cell lung cancer (NSCLC) is a rare event with favorable prognosis, but the clinical outcome has not been fully determined. We retrospectively analyzed clinical outcomes and prognostic factors in metachronous brain-only oligorecurrence in patients with NSCLC who underwent definitive treatment.

Materials And Methods: We reviewed 4,437 NSCLC patients without oncogenic driver mutations who underwent definitive treatment between 2008 and 2018. Among them, we identified 327 patients who developed 1 to 5 brain metastases with or without systemic metastasis. Of the 327 patients, 71 had metachronous brain-only oligorecurrence without extracranial progression and were treated with local therapy to the brain. Overall survival (OS), progression-free survival (PFS), and prognostic factors affecting OS were analyzed.

Results: The median OS was 38.9 months (95% CI, 21.8 to 56.1 months) in 71 patients. The 2-year OS rate was 67.8% and the 5-year OS rate was 33.1%. The median PFS was 25.5 months (95% CI, 12.2 to 14.4 months). The longest surviving patient had a survival period of 115 months. Through multivariate analysis, ECOG ≥ 1 (HR: 5.33, p=0.005) was associated with poor survival. There was no significant difference in OS between patients with local therapy and those with local plus systemic therapy (18.5 vs. 34.7 months, p=0.82).

Conclusion: Metachronous brain-only oligorecurrence NSCLC patients who underwent definitive treatment experienced long-term survival with local therapy, highlighting the unique patient population. The role of systemic chemotherapy in this patient population requires further investigation.
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http://dx.doi.org/10.4143/crt.2021.306DOI Listing
May 2021

Multimodal treatments and outcomes for anaplastic thyroid cancer before and after tyrosine kinase inhibitor therapy: a real-world experience.

Eur J Endocrinol 2021 May 6;184(6):837-845. Epub 2021 May 6.

Division of Endocrinology and Metabolism, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Anaplastic thyroid cancer (ATC) has dismal prognosis and there is no effective treatment. We aimed to evaluate the efficacy of tyrosine kinase inhibitor (TKI) therapy in real-world clinic and to suggest the most effective treatment modality according to the combination of treatments.

Methods: This retrospective study evaluated clinical outcomes and cause of death with multimodal treatments in patients with ATC at Samsung Medical Center.

Results: A total of 120 patients received anti-cancer treatment for ATC. Seventy-seven (64.2%) patients underwent surgery, 64 (53.3%) received radiotherapy, 29 (24.2%) received cytotoxic chemotherapy, and 19 (15.8%) received TKI therapy. In the TKI therapy group, eight achieved partial response (three with lenvatinib and five with dabrafenib plus trametinib), and two patients with lenvatinib showed stable disease. Median progression-free survival (PFS) of the TKI therapy group was 2.7 months (range: 0.1-12.7) and their median overall survival (OS) was 12.4 months (range: 1.7-47.7). Patients who received surgery or radiotherapy for local control showed superior OS than those who did not. In a multivariate analysis, surgery, TKI therapy, younger age, and no distant metastasis were associated with favorable OS. The combination of surgery, radiotherapy, and TKI therapy (median OS: 34.3 months, 6-month survival rates: 77.8%) was the most effective. Compared to the era without TKI therapy, distant metastasis has recently become the major cause of death in ATC over airway problems.

Conclusions: Multimodality treatment including TKI therapy demonstrated prolonged survival with dabrafenib plus trametinib as the most effective therapeutic option demonstrated for BRAF mutant ATC patients.
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http://dx.doi.org/10.1530/EJE-20-1482DOI Listing
May 2021

High concordance of actionable genomic alterations identified between circulating tumor DNA-based and tissue-based next-generation sequencing testing in advanced non-small cell lung cancer: The Korean lung liquid versus invasive biopsy program.

Cancer 2021 Apr 7. Epub 2021 Apr 7.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background: Because of the growing number of actionable biomarkers in non-small cell lung cancer (NSCLC), sufficient tissue availability for testing is becoming a greater challenge. Liquid biopsy offers a potential solution by complementing standard tissue-based methods. In this study, the authors analyzed the concordance of actionable genomic alterations sequenced from circulating tumor DNA (ctDNA; Guardant360) and tissue (Oncomine Focus Assay).

Methods: From September 2015 to May 2018, 421 paired plasma and tissue samples from patients with advanced NSCLC who had previously undergone tissue testing by standard methods were collected. Both types of samples were available for 287 patients (262 in cohort 1 [treatment-naive] and 25 in cohort 2 [treatment failure]), and only 1 sample type was available for 134 patients (50 in cohort 3 [plasma only] and 84 in cohort 4 [tissue only]).

Results: In cohort 1, 198 samples (77.6%) showed concordance between tissue and plasma next-generation sequencing (NGS). Among the discordant cases, plasma testing detected additional genomic alterations in 11 patients (4.2%). In 50 patients without tissue-based NGS results (cohort 3), the ctDNA-based test detected genomic alterations in 20 samples (40.0%). The median allele frequency (AF) of mutations identified with ctDNA-based NGS (0.74%) was lower than that identified with the tissue-based NGS test (13.90%). Clinical responses to matched targeted therapy occurred, regardless of the ctDNA AF. Upfront ctDNA-based testing identified 60.4% of patients with genomic alterations. In addition, ctDNA-based testing uncovered 12.0% more actionable alterations when it was performed after tissue-based NGS testing.

Conclusions: The results indicate that a ctDNA-based test identifies additional patients with actionable genomic alterations and could, therefore, be used to complement traditional tissue-based testing for NSCLC.

Lay Summary: Circulating tumor DNA (ctDNA)-based next-generation sequencing (NGS) testing is becoming essential as the number of actionable genomic biomarker increases for the treatment selection of non-small cell lung cancer. This study demonstrates the additive value of ctDNA-based testing in addition to tissue-based NGS and standard of care-based biomarker testing for detecting additional patients with actionable genomic alterations. Clinical responses have also been observed in patients with a low allele frequency detected by ctDNA-based NGS testing.
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http://dx.doi.org/10.1002/cncr.33571DOI Listing
April 2021

Patient-Reported Outcomes with Durvalumab With or Without Tremelimumab Versus Standard Chemotherapy as First-Line Treatment of Metastatic Non-Small-Cell Lung Cancer (MYSTIC).

Clin Lung Cancer 2021 Feb 19. Epub 2021 Feb 19.

Division of Hematology/Oncology, Columbia University Medical Center, New York, NY.

Background: The phase 3 MYSTIC study of durvalumab ± tremelimumab versus chemotherapy in metastatic non-small-cell lung cancer (NSCLC) patients with tumor cell (TC) programmed cell death ligand 1 (PD-L1) expression ≥ 25% did not meet its primary endpoints. We report patient-reported outcomes (PROs).

Patients And Methods: Treatment-naïve patients were randomized (1:1:1) to durvalumab, durvalumab + tremelimumab, or chemotherapy. PROs were assessed in patients with PD-L1 TC ≥ 25% using EORTC Quality of Life Questionnaire (QLQ)-C30/LC13. Changes from baseline (12 months) for prespecified PRO endpoints of interest were analyzed by mixed model for repeated measures (MMRM) and time to deterioration (TTD) by stratified log-rank tests.

Results: There were no between-arm differences in baseline PROs (N = 488). Between-arm differences in MMRM-adjusted mean changes from baseline favored at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for C30 fatigue: durvalumab (-9.5; 99% confidence interval [CI], -17.0 to -2.0), durvalumab + tremelimumab (-11.7; 99% CI, -19.4 to -4.1); and for C30 appetite loss: durvalumab (-11.9; 99% CI, -21.1 to -2.7). TTD was longer with at least one of the durvalumab-containing arms versus chemotherapy (nominal P < .01) for global health status/quality of life: durvalumab (hazard ratio [HR] = 0.7; 95% CI, 0.5-1.0), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0); and for physical functioning: durvalumab (HR = 0.6; 95% CI, 0.4-0.8), durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.5-0.9) (both C30); as well as for the key symptoms of dyspnea: durvalumab (HR = 0.6; 95% CI, 0.5-0.9), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-1.0) (both LC13); fatigue: durvalumab + tremelimumab (HR = 0.6; 95% CI, 0.4-0.8); and appetite loss: durvalumab (HR = 0.5; 95% CI, 0.4-0.7), durvalumab + tremelimumab (HR = 0.7; 95% CI, 0.5-0.9) (both C30).

Conclusion: Durvalumab ± tremelimumab versus chemotherapy reduced symptom burden and improved TTD of PROs, suggesting it had no detrimental effects on quality of life in metastatic NSCLC patients.
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http://dx.doi.org/10.1016/j.cllc.2021.02.010DOI Listing
February 2021

Tipifarnib in Head and Neck Squamous Cell Carcinoma With Mutations.

J Clin Oncol 2021 Mar 22:JCO2002903. Epub 2021 Mar 22.

Kura Oncology, Boston, MA.

Purpose: Mutations in the (m) proto-oncogene occur in 4%-8% of patients with recurrent and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). Tipifarnib is a farnesyltransferase inhibitor that disrupts function. We evaluated the efficacy of tipifarnib in patients with R/M m HNSCC.

Methods: We enrolled 30 patients with R/M HNSCC in a single-arm, open-label phase II trial of tipifarnib for m malignancies; one additional patient was treated on an expanded access program. After an ad hoc analysis of the first 16 patients with HNSCC with m variant allele frequency (VAF) data, enrollment was limited to those with a m VAF of ≥ 20% (high VAF). The primary end point was objective response rate. Secondary end points included assessing safety and tolerability. Patients received tipifarnib 600 or 900 mg orally twice daily on days 1-7 and 15-21 of 28-day cycles.

Results: Of the 22 patients with HNSCC with high VAF, 20 were evaluable for response at the time of data cutoff. Objective response rate for evaluable patients with high-VAF HNSCC was 55% (95% CI, 31.5 to 76.9). Median progression-free survival on tipifarnib was 5.6 months (95% CI, 3.6 to 16.4) versus 3.6 months (95% CI, 1.3 to 5.2) on last prior therapy. Median overall survival was 15.4 months (95% CI, 7.0 to 29.7). The most frequent treatment-emergent adverse events among the 30 patients with HNSCC were anemia (37%) and lymphopenia (13%).

Conclusion: Tipifarnib demonstrated encouraging efficacy in patients with R/M HNSCC with mutations for whom limited therapeutic options exist (NCT02383927).
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http://dx.doi.org/10.1200/JCO.20.02903DOI Listing
March 2021

Comprehensive evaluation of the clinical utility of plasma EGFR test in non-small cell lung cancer patients with acquired resistance to first-line EGFR inhibitors.

Transl Lung Cancer Res 2021 Feb;10(2):878-888

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Background: Plasma epidermal growth factor receptor (EGFR) mutation tests are widely used when non-small cell lung cancer (NSCLC) patients acquire resistance to EGFR inhibitors. We comprehensively evaluated the clinical utility of plasma EGFR test.

Methods: We screened NSCLC patients who had a plasma EGFR test upon acquiring resistance to first- or second-generation EGFR inhibitors. Plasma EGFR tests were performed with the EGFR mutation test.

Results: A total of 355 patients were tested for plasma EGFR mutations, and T790M was detected in 83 patients (23%). Of 79 patients who were tested multiple times, T790M was newly detected in 13 subsequent plasma tests. When initial plasma tests did not detect any EGFR mutation types, the detection rate of T790M in subsequent tests was very low (9%, 5/56), while detection rates of T790M in subsequent tests increased (35%, 8/23) in those individuals in whom sensitizing mutations had been detected in the initial plasma test (P=0.005). Paired plasma and tissue EGFR test results were available for 235 patients. Sensitivity and specificity of the plasma tests for T790M were 14% and 87%, respectively. Among 235 patients, 140 patients had tissue EGFR tests performed after T790M-negative plasma results were reported. The subsequent tissue test detected T790M in 61% (44/72) of these patients when any EGFR mutations were not detected in prior plasma tests, while the detection rate of T790M in subsequent tissue tests was 37% (25/68) when sensitizing mutations were detected in prior plasma tests (P=0.004).

Conclusions: Because the sensitivity of plasma EGFR test for T790M is low, follow-up tissue or plasma tests are necessary. Presence or absence of a sensitizing mutation in the initial plasma tests can be used to determine which samples (tissue or plasma) should be submitted for further testing.
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http://dx.doi.org/10.21037/tlcr-20-1128DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947405PMC
February 2021

Updated Integrated Analysis of the Efficacy and Safety of Entrectinib in Locally Advanced or Metastatic Fusion-Positive Non-Small-Cell Lung Cancer.

J Clin Oncol 2021 Apr 1;39(11):1253-1263. Epub 2021 Mar 1.

Aix Marseille University, CNRS, INSERM, CRCM, APHM, Marseille, France.

Purpose: Genetic rearrangements of the tyrosine receptor kinase ROS proto-oncogene 1 () are oncogenic drivers in non-small-cell lung cancer (NSCLC). We report the results of an updated integrated analysis of three phase I or II clinical trials (ALKA-372-001, STARTRK-1, and STARTRK-2) of the ROS1 tyrosine kinase inhibitor, entrectinib, in fusion-positive NSCLC.

Methods: The efficacy-evaluable population included adults with locally advanced or metastatic fusion-positive NSCLC with or without CNS metastases who received entrectinib ≥ 600 mg orally once per day. Co-primary end points were objective response rate (ORR) assessed by blinded independent central review and duration of response (DoR). Secondary end points included progression-free survival (PFS), overall survival (OS), intracranial ORR, intracranial DoR, intracranial PFS, and safety.

Results: In total, 161 patients with a follow-up of ≥ 6 months were evaluable. The median treatment duration was 10.7 months (IQR, 6.4-17.7). The ORR was 67.1% (n = 108, 95% CI, 59.3 to 74.3), and responses were durable (12-month DoR rate, 63%, median DoR 15.7 months). The 12-month PFS rate was 55% (median PFS 15.7 months), and the 12-month OS rate was 81% (median OS not estimable). In 24 patients with measurable baseline CNS metastases by blinded independent central review, the intracranial ORR was 79.2% (n = 19; 95% CI, 57.9 to 92.9), the median intracranial PFS was 12.0 months (95% CI, 6.2 to 19.3), and the median intracranial DoR was 12.9 months (12-month rate, 55%). The safety profile in this updated analysis was similar to that reported in the primary analysis, and no new safety signals were found.

Conclusion: Entrectinib continued to demonstrate a high level of clinical benefit for patients with fusion-positive NSCLC, including patients with CNS metastases.
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http://dx.doi.org/10.1200/JCO.20.03025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8078299PMC
April 2021

Global longitudinal assessment of treatment outcomes in recurrent/metastatic nasopharyngeal carcinoma: GLANCE-NPC study.

Future Oncol 2021 Feb 19. Epub 2021 Feb 19.

Department of Medicine, Taipei Veterans General Hospital, Division of Medical Oncology, Taipei, 112, Taiwan.

Given a lack of standard of care treatment for recurrent/metastatic nasopharyngeal carcinoma (R/M NPC), we assessed treatment patterns and overall survival in the real-world setting. A retrospective chart review was conducted in patients who initiated first-line systemic therapy in Taiwan and South Korea between January 2012 and June 2013 with follow-up through December 2015. Among 154 R/M NPC patients, all patients in Taiwan (n = 104) had distant metastases, whereas in South Korea (n = 50) 42% had distant metastases. Patients with distant metastases generally received systemic therapy only (71%) for whom median overall survival was 23 months (95% CI: 18-32). Prognosis in R/M NPC with distant metastases remains poor, underscoring the need for more efficacious treatments.
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http://dx.doi.org/10.2217/fon-2020-1087DOI Listing
February 2021

ALTA-2: Phase II study of brigatinib in patients with ALK-positive, advanced non-small-cell lung cancer who progressed on alectinib or ceritinib.

Future Oncol 2021 May 11;17(14):1709-1719. Epub 2021 Feb 11.

Chao Family Comprehensive Cancer Center, University of California Irvine School of Medicine, Orange, CA 92868, USA.

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved outcomes in -rearranged (ALK+) non-small-cell lung cancer (NSCLC). However, almost all patients eventually develop progressive disease on first-line ALK TKIs (e.g., crizotinib, alectinib and ceritinib). Brigatinib, a second-generation ALK TKI, may show efficacy in alectinib- and ceritinib-refractory ALK+ NSCLC. We describe the rationale and design of ALTA-2, a Phase II study of brigatinib in patients with locally advanced/metastatic ALK+ NSCLC and documented progressive disease on alectinib or ceritinib. The primary end point is confirmed objective response rate per independent review committee using response evaluation criteria in solid tumors version 1.1. Secondary end points include duration of response, progression-free survival, overall survival, safety and health-related quality of life.
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http://dx.doi.org/10.2217/fon-2020-1119DOI Listing
May 2021

Real-world outcomes of anti-PD1 antibodies in platinum-refractory, PD-L1-positive recurrent and/or metastatic non-small cell lung cancer, and its potential practical predictors: first report from Korean Cancer Study Group LU19-05.

J Cancer Res Clin Oncol 2021 Feb 1. Epub 2021 Feb 1.

Department of Medical Oncology, Seoul St. Mary's Hospital, The Catholic University, 222 Banpo-daero, Seocho-gu, Seoul, 06591, Republic of Korea.

Purpose: Although immune-checkpoint inhibitors have become a new therapeutic option for recurrent/metastatic non-small cell lung cancers (R/M-NSCLC), its clinical benefit in the real-world is still unclear.

Methods: We investigated 1181 Korean patients with programmed death-1 ligand 1 (PD-L1)-positive [tumor proportion score (TPS) ≥ 10% by the SP263 assay or ≥ 50% by the 22C3 assay] R/M-NSCLC treated with pembrolizumab or nivolumab after failure of platinum-based chemotherapy.

Results: The median age was 67 years, 13% of patients had ECOG-PS ≥ 2, and 27% were never-smokers. Adenocarcinoma was predominant (61%) and 18.1% harbored an EGFR activating mutation or ALK rearrangement. Pembrolizumab and nivolumab were administered to 51.3% and 48.7, respectively, and 42% received them beyond the third-line chemotherapy. Objective response rate (ORR) was 28.6%. Pembrolizumab group showed numerically higher ORR (30.7%) than the nivolumab group (26.4%), but it was comparable with that of the nivolumab group having PD-L1 TPS ≥ 50% (32.4%). Median progression-free survival (PFS) and overall survival (OS) were 2.9 (95% CI 0-27.9) and 10.7 months (95% CI 0-28.2), respectively. In multivariable analysis, concordance of TPS ≥ 50% in both PD-L1 assays and the development of immune-related adverse events (irAEs) were two significant predictors of better ORR, PFS, and OS. EGFR mutation could also predict significantly worse OS outcomes.

Conclusion: The real-world benefit of later-line anti-PD1 antibodies was comparable to clinical trials in patients with R/M-NSCLC, although patients generally were more heavily pretreated and had poorer ECOG-PS. Concordantly high PD-L1 TPS ≥ 50% and development of irAE could independently predict better treatment outcomes, while EGFR mutation negatively affected OS.
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http://dx.doi.org/10.1007/s00432-021-03527-4DOI Listing
February 2021

Tumor infiltrated immune cell types support distinct immune checkpoint inhibitor outcomes in patients with advanced non-small cell lung cancer.

Eur J Immunol 2021 Apr 22;51(4):956-964. Epub 2021 Feb 22.

Division of Hematology-Oncology, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea.

The evaluation of PD-L1 expression alone has limitations in predicting clinical outcome in immune-checkpoint inhibitors (ICI). This study aimed to evaluate the predictive and prognostic effects of the presence of various immune cells in pretreatment tissue samples and to identify determinants associated with response in patients with advanced non-small cell lung cancer (NSCLC) treated with PD-1 blockade. Immune cell distribution was heterogeneous and the most dominant immune cell type was T cells. Patients with durable clinical benefit (DCB) showed significantly higher PD-L1 expression. The ratio of tumor/stroma region of T cell, B cell, and macrophage was significantly higher in patient with DCB. High intratumoral T- and B-cell density (≥median) was associated with DCB in the low PD-L1 expression (<50%) group. In univariate analyses, the overall survival (OS) benefit was shown according to intratumoral B-cell density (p = 0.0337). The incidence of hyperprogressive disease (HPD) was 13.0%. The Chi-square test revealed that HPD was significantly associated with intratumoral B-cell density but not T-cell or macrophage density. Our results demonstrate different predictive and prognostic values for infiltrating immune cells in tumor tissue, which may help in selecting patients for ICI.
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http://dx.doi.org/10.1002/eji.202048966DOI Listing
April 2021

A Response to the Letter to the Editor: Osimertinib Leads the Way Towards Improving Outcomes of EGFR-Mutant NSCLC With Leptomeningeal Metastases.

J Thorac Oncol 2021 02;16(2):e14

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jtho.2020.12.009DOI Listing
February 2021

Immunological Characteristics of Hyperprogressive Disease in Patients with Non-small Cell Lung Cancer Treated with Anti-PD-1/PD-L1 Abs.

Immune Netw 2020 Dec 21;20(6):e48. Epub 2020 Dec 21.

Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 34141, Korea.

Hyperprogressive disease (HPD) is a distinct pattern of progression characterized by acceleration of tumor growth after treatment with anti-PD-1/PD-L1 Abs. However, the immunological characteristics have not been fully elucidated in patients with HPD. We prospectively recruited patients with metastatic non-small cell lung cancer treated with anti-PD-1/PD-L1 Abs between April 2015 and April 2018, and collected peripheral blood before treatment and 7-days post-treatment. HPD was defined as ≥2-fold increase in both tumor growth kinetics and tumor growth rate between pre-treatment and post-treatment. Peripheral blood mononuclear cells were analyzed by multi-color flow cytometry to phenotype the immune cells. Of 115 patients, 19 (16.5%) developed HPD, 52 experienced durable clinical benefit (DCB; partial response or stable disease ≥6 months), and 44 experienced non-hyperprogressive progression (NHPD). Patients with HPD had significantly lower progression-free survival (p<0.001) and overall survival (p<0.001). When peripheral blood immune cells were examined, the pre-treatment frequency of CD39 cells among CD8 T cells was significantly higher in patients with HPD compared to those with NHPD, although it showed borderline significance to predict HPD. Other parameters regarding regulatory T cells or myeloid derived suppressor cells did not significantly differ among patient groups. Our findings suggest high pre-treatment frequency of CD39CD8 T cells might be a characteristic of HPD. Further investigations in a larger cohort are needed to confirm our results and better delineate the immune landscape of HPD.
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http://dx.doi.org/10.4110/in.2020.20.e48DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7779871PMC
December 2020

Recent Advances on the Role of EGFR Tyrosine Kinase Inhibitors in the Management of NSCLC With Uncommon, Non Exon 20 Insertions, EGFR Mutations.

J Thorac Oncol 2021 May 14;16(5):764-773. Epub 2020 Dec 14.

Division of Thoracic Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.

The first-line treatment of choice for patients with EGFR mutation-positive NSCLC is an EGFR tyrosine kinase inhibitor (TKI), of which five as follows are predominantly available in practice: gefitinib, erlotinib, afatinib, dacomitinib, and osimertinib. Most prospective clinical trial data with these agents are limited to patients with the common activating and sensitizing EGFR mutations as follows: exon 19 deletions and exon 21 L858R point mutations. However, 10% to 20% of patients with NSCLC harbor uncommon EGFR mutations that have variable sensitivity to different EGFR TKIs. Owing to their molecular structures, afatinib, dacomitinib, and osimertinib have broader inhibitory profiles than the first-generation agents, gefitinib and erlotinib. Nevertheless, the paucity of prospective clinical data, the wide heterogeneity of uncommon mutations, and the existence of compound mutations in up to 25% of the cases complicate treatment decisions in this patient subgroup. Here, we collate the latest preclinical and clinical data regarding the activity of different TKIs against major uncommon EGFR mutations including compound mutations, but excluding exon 20 insertions which are generally insensitive to TKIs. On the basis of these data, we offer suggestions regarding treatment strategies for uncommon EGFR mutations. Moving forward, it will be important to include uncommon EGFR mutations in the first-line molecular analysis of all patients with adenocarcinoma of the lung, as this will help optimize patient outcomes according to their precise genotype.
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http://dx.doi.org/10.1016/j.jtho.2020.12.002DOI Listing
May 2021

Dynamic contrast-enhanced MRI for response evaluation of non-small cell lung cancer in therapy with epidermal growth factor receptor tyrosine kinase inhibitors: a pilot study.

Ann Palliat Med 2021 Feb 25;10(2):1589-1598. Epub 2020 Nov 25.

Department of Radiology and the Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: It is important to identify candidates who would benefit from target agent chemotherapy in advanced NSCLC patients. The purpose of this study is to evaluate the feasibility of DCE-MRI for early response evaluation in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) treatment in patients with NSCLC.

Methods: Seven patients were prospectively enrolled who have pathologically-proven NSCLC with EGFR mutations or at least 2 of the following factors; adenocarcinoma, female, or never-smokers. Patients were treated with gefitinib or erlotinib and the start of chemotherapy was denoted day 0. DCE-MRI was performed at day-1, day+7, and day+28. Longitudinal changes of perfusion parameters were quantified and compared to Response Evaluation Criteria in Solid Tumors (RECIST) results.

Results: Quantitative perfusion parameters; Ktrans, ve and vp of the lung cancer showed a significant decrease at day+7 (P=0.016), but no further significant decrease between day+7 and day+28 (P>0.05). Semiquantitative markers for tumor enhancement curve pattern; EA (enhancement amplitude), MS (maximum slope), and AUC (area under the curve) also showed a significant decrease at day+7 (P=0.016, 0.031, and 0.016, respectively), but no further significant decrease between day+7 and day+28 (P>0.05). When RECIST applied, all patient was in the stable disease at day+7 and three patients showed partial response (PR) at day+28. All seven patients showed PR by the 3-month follow-up.

Conclusions: Perfusion parameters may be used as an early non-invasive imaging biomarker for the response evaluation of target agent treatment in NSCLC.
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http://dx.doi.org/10.21037/apm-19-622DOI Listing
February 2021

Outcomes and Biomarkers of Immune Checkpoint Inhibitor Therapy in Patients with Refractory Head and Neck Squamous Cell Carcinoma: KCSG HN18-12.

Cancer Res Treat 2020 Dec 7. Epub 2020 Dec 7.

Department of Internal Medicine, Chung-Ang University Hospital, Chung-Ang University College of Medicine, Seoul, Korea.

Purpose: This study was conducted to determine the effectiveness of immune checkpoint inhibitors (ICIs) in recurrent or metastatic head and neck squamous cell cancer (R/M HNSCC) after platinum-containing chemotherapy. We also identified clinical biomarkers which may be predictive of patient prognosis.

Materials And Methods: We analyzed 125 patients with R/M HNSCC who received ICIs, retrospectively. Overall response rate (ORR) was the primary study outcome. Overall survival (OS) and progression-free survival (PFS) were the secondary study outcomes.

Results: The patients received anti‒programmed cell death protein-1 (PD-1) (n=73, 58%), anti‒programmed death-ligand 1 (PD-L1) (n=24, 19%), or a combination of anti-PD-1/PD-L1 and anti‒cytotoxic T-lymphocyte antigen 4 (n=28, 22%). The median age was 57 (range, 37 to 87). The location of the primary tumor was in the oral cavity in 28% of the cases, followed by oropharynx (27%), hypopharynx (20%), and larynx (12%). The ORR was 15% (19/125). With 12.3 months of median follow-up, median PFS was 2.7 months. Median OS was 10.8 months. A neutrophil-to-lymphocyte ratio (NLR) >4 was significantly associated with poor response to ICIs (odds ratio, 0.30; p=0.022). A sum of the target lesions > 40 mm (hazard ratio [HR], 1.53; p=0.046] and a NLR > 4 (HR, 1.75; p=0.009) were considered to be predictive markers of short PFS. A poor performance status (HR, 4.79; p < 0.001), a sum of target lesions > 40 mm (HR, 1.93; p=0.025), and an NLR > 4 (HR, 3.36; p < 0.001) were the significant predictors for poor survival.

Conclusion: ICIs exhibited favorable antitumor activity in R/M HNSCC. Clinically, our findings can be used to recognize patients benefit from receiving ICI.
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http://dx.doi.org/10.4143/crt.2020.824DOI Listing
December 2020

Immune Checkpoint Inhibitors for Non-Small-Cell Lung Cancer with Brain Metastasis : The Role of Gamma Knife Radiosurgery.

J Korean Neurosurg Soc 2021 Mar 4;64(2):271-281. Epub 2020 Dec 4.

Department of Neurosurgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Objective: Immune checkpoint inhibitors (ICIs) are approved for treating non-small-cell lung cancer (NSCLC); however, the safety and efficacy of combined ICI and Gamma Knife radiosurgery (GKS) treatment remain undefined. In this study, we retrospectively analyzed patients treated with ICIs with or without GKS at our institute to manage patients with brain metastases from NSCLC.

Methods: We retrospectively reviewed medical records of patients with brain metastases from NSCLC treated with ICIs between January 2015 and December 2017. Of 134 patients, 77 were assessable for brain responses and categorized into three groups as follows : group A, ICI alone (n=26); group B, ICI with concurrent GKS within 14 days (n=24); and group C, ICI with non-concurrent GKS (n=27).

Results: The median follow-up duration after brain metastasis diagnosis was 19.1 months (range, 1-77). At the last follow-up, 53 patients (68.8%) died, 20 were alive, and four were lost to follow-up. The estimated median overall survival (OS) of all patients from the date of brain metastasis diagnosis was 20.0 months (95% confidence interval, 12.5-27.7) (10.0, 22.5, and 42.1 months in groups A, B, and C, respectively). The OS was shorter in group A than in group C (p=0.001). The intracranial disease progression-free survival (p=0.569), local progression-free survival (p=0.457), and complication rates did not significantly differ among the groups. Twelve patients showed leptomeningeal seeding (LMS) during follow-up. The 1-year LMS-free rate in treated with ICI alone group (69.1%) was significantly lower than that in treated with GKS before ICI treatment or within 14 days group (93.2%) (p=0.004).

Conclusion: GKS with ICI showed no favorable OS outcome in treating brain metastasis from NSCLC. However, GKS with ICI did not increase the risk of complications. Furthermore, compared with ICI alone, GKS with ICI may be associated with a reduced incidence of LMS. Further understanding of the mechanism, which remains unknown, may help improve the quality of life of patients with brain metastasis.
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http://dx.doi.org/10.3340/jkns.2020.0135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969051PMC
March 2021

The different central nervous system efficacy among gefitinib, erlotinib and afatinib in patients with epidermal growth factor receptor mutation-positive non-small cell lung cancer.

Transl Lung Cancer Res 2020 Oct;9(5):1749-1758

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Background: Brain metastasis is common in non-small cell lung cancer (NSCLC) and has an even higher incidence in epidermal growth factor receptor (EGFR)-mutant cancers. Although EGFR tyrosine kinase inhibitors (TKIs) are effective against brain metastases, it is unknown which first- or second-generation EGFR TKI is most effective.

Methods: Patients treated with first-line gefitinib, erlotinib, or afatinib for advanced EGFR-mutant NSCLC were included. The efficacy against brain metastasis was evaluated by comparing the response rates of measurable and non-irradiated brain metastases, central nervous system progression-free survival (CNS-PFS), and the cumulative incidence of CNS failure.

Results: Among the 559 patients who received EGFR-TKIs (gefitinib, n=299; erlotinib, n=93; afatinib, n=167), 198 had initial brain metastasis before starting EGFR-TKIs. The CNS response rates of gefitinib, erlotinib, and afatinib were 64.7%, 68.2%, and 72.9%, respectively (P=0.78). In the overall study population, irrespective of initial CNS metastasis, the median CNS-PFS was 17.3 months for gefitinib, 12.4 months for erlotinib, and 23.3 months for afatinib (P<0.001). In multivariate analysis for CNS-PFS, the hazard ratio (HR) of afatinib was 0.63 (95% CI, 0.47-0.83) compared with gefitinib or erlotinib. In the competing risk analysis for cumulative incidence of CNS failure, afatinib showed a lower cumulative incidence of CNS failure compared with gefitinib or erlotinib after adjusting for both EGFR mutation type and preexisting CNS metastases (HR 0.51, 95% CI, 0.34-0.75, P=0.0007).

Conclusions: Through there are some limitation as a retrospective study, afatinib showed similar CNS response rates, superior CNS-PFS and cumulative incidence of CNS failure, compared with gefitinib or erlotinib.
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http://dx.doi.org/10.21037/tlcr-20-379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653133PMC
October 2020

An increase of CD8 T cell infiltration following recurrence is a good prognosticator in HNSCC.

Sci Rep 2020 11 18;10(1):20059. Epub 2020 Nov 18.

Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea.

Programmed death-ligand 1 (PD-L1) expression and CD8-positive tumor-infiltrating lymphocyte (CD8 TIL) infiltration are essential biomarkers for immune checkpoint inhibitor therapy. The objective of this study was to compare the expression of those biomarkers between initial and recurrent HNSCCs using paired analysis. Prognostic significance of those immunological changes was also investigated. Forty-two consecutive patients with locally recurrent HNSCCs were included. Immunohistochemical staining of CD8 and PD-L1 was done for both initial and recurrent tumor specimens. The IHC findings were verified with mRNA expression profiling. Also, the prognostic impact was analyzed based on overall survival (OS). Recurrent-to-initial (R/I) ratios of CD8 TILs and PD-L1 were widely variable. CD8 TIL density and PD-L1 expression decreased in 59.5% and 69% of patients, respectively (R/I ratio < 1). The R/I ratio of CD8A mRNA was significantly higher in patients with a CD8 R/I ratio > 1 (1.7 ± 1.5 vs. 0.6 ± 0.6, p = 0.042). CD8 R/I ratio (> 1) was a good prognosticator for OS (HR 0.293, 95% CI 0.091-0.945, p = 0.040). CD8 TIL infiltration and PD-L1 expression changed variably following local recurrence of HNSCC. The increase of CD8 TILs at recurrence was an excellent independent prognosticator.
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http://dx.doi.org/10.1038/s41598-020-77036-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674485PMC
November 2020

Immune checkpoint inhibitors in driver mutation-positive nonsmall cell lung cancer: is there a role?

Curr Opin Oncol 2021 Jan;33(1):64-72

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose Of Review: Despite advances in immunotherapy for nonsmall cell lung cancer patients, the clinical efficacy of drugs for patients with oncogenic driver mutations remains limited. This article aimed to comprehensively review the currently available data on the efficacy and safety of immune checkpoint blockade (ICB) for patients with driver mutation-positive lung cancer.

Recent Findings: Despite the positive interaction between activation of oncogenic pathways and upregulated PD-L1 expression demonstrated in preclinical studies, the efficacy of single-agent ICB in patients with oncogenic mutation has largely been discouraging, except for those with KRAS mutations. The combination therapies using ICB with tyrosine kinase inhibitors (TKIs) for EGFR/ALK alteration raised a concern for the high incidence of treatment-related adverse events, notably hepatotoxicity and interstitial lung disease. A novel combination with bevacizumab demonstrated promising efficacy with tolerable safety profiles.

Summary: Other than patients with the KRAS mutation who demonstrate relatively favorable response to ICB, a single-agent ICB therapy should be considered for those who retain good performance status but have no other therapeutic options available. Further studies on the combination of ICB and TKI are needed to identify the most viable pair regarding safety. Additional studies using novel combination partners, such as anti-VEGF inhibitors, are also warranted.
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http://dx.doi.org/10.1097/CCO.0000000000000698DOI Listing
January 2021

Regulatory (FoxP3) T cells and TGF-β predict the response to anti-PD-1 immunotherapy in patients with non-small cell lung cancer.

Sci Rep 2020 11 4;10(1):18994. Epub 2020 Nov 4.

Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 81 Irwon-ro, Gangnam-gu, Seoul, Republic of Korea.

Antitumor immune responses induced by immune checkpoint inhibitors anti-PD-1 or anti-PD-L1 have been used as therapeutic strategies in advanced non-small cell lung cancer (NSCLC) patients over the last decade. Favorable antitumor activity to immune checkpoint inhibitors is correlated with high PD-L1 expression, increased tumor-infiltrating lymphocytes, and decreased suppressive immune cells including Treg cells, myeloid-derived suppressor cells, or tumor-associated macrophages in various cancer types. In this study, we investigated the potential correlation between clinical outcomes and peripheral blood immune cell profiles, specifically focused on FoxP3 Treg cells, collected at baseline and one week after anti-PD-1 therapy in two independent cohorts of patients with NSCLC: a discovery cohort of 83 patients and a validation cohort of 49 patients. High frequencies of circulating Treg cells one week after anti-PD-1 therapy were correlated with a high response rate, longer progression-free survival, and overall survival. Furthermore, high levels of TGF-β and Treg cells were associated with favorable clinical outcomes. Our results suggest that higher levels of FoxP3 Treg cells and TGF-β can predict a favorable response to anti-PD-1 immunotherapy in patients with advanced NSCLC.
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http://dx.doi.org/10.1038/s41598-020-76130-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642363PMC
November 2020

Clinical advantage of targeted sequencing for unbiased tumor mutational burden estimation in samples with low tumor purity.

J Immunother Cancer 2020 10;8(2)

Samsung Genome Institute, Samsung Medical Center, Seoul, Korea

Background: Tumor mutational burden (TMB) measurement is limited by low tumor purity of samples, which can influence prediction of the immunotherapy response, particularly when using whole-exome sequencing-based TMB (wTMB). This issue could be overcome by targeted panel sequencing-based TMB (pTMB) with higher depth of coverage, which remains unexplored.

Methods: We comprehensively reanalyzed four public datasets of immune checkpoint inhibitor (ICI)-treated cohorts (adopting pTMB or wTMB) to test each biomarker's predictive ability for low purity samples (cut-off: 30%). For validation, paired genomic profiling with the same tumor specimens was performed to directly compare wTMB and pTMB in patients with breast cancer (paired-BRCA, n=165) and ICI-treated patients with advanced non-small-cell lung cancer (paired-NSCLC, n=156).

Results: Low tumor purity was common (range 30%-45%) in real-world samples from ICI-treated patients. In the survival analyzes of public cohorts, wTMB could not predict the clinical benefit of immunotherapy when tumor purity was low (log-rank p=0.874), whereas pTMB could effectively stratify the survival outcome (log-rank p=0.020). In the paired-BRCA and paired-NSCLC cohorts, pTMB was less affected by tumor purity, with significantly more somatic variants identified at low allele frequency (p<0.001). We found that wTMB was significantly underestimated in low purity samples with a large proportion of clonal variants undetected by whole-exome sequencing. Interestingly, pTMB more accurately predicted progression-free survival (PFS) after immunotherapy than wTMB owing to its superior performance in the low tumor purity subgroup (p=0.054 vs p=0.358). Multivariate analysis revealed pTMB (p=0.016), but not wTMB (p=0.32), as an independent predictor of PFS even in low-purity samples. The net reclassification index using pTMB was 21.7% in the low-purity subgroup (p=0.016).

Conclusions: Our data suggest that TMB characterization with targeted deep sequencing might have potential strength in predicting ICI responsiveness due to its enhanced sensitivity for hard-to-detect variants at low-allele fraction. Therefore, pTMB could act as an invaluable biomarker in the setting of both clinical trials and practice outside of trials based on its reliable performance in mitigating the purity-related bias.
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http://dx.doi.org/10.1136/jitc-2020-001199DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574938PMC
October 2020

Treatment and Outcomes of Metastatic Non-Small-Cell Lung Cancer Harboring Uncommon Mutations: Are They Different from Those with Common Mutations?

Biology (Basel) 2020 Oct 7;9(10). Epub 2020 Oct 7.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 06351, Korea.

Approximately 10% of the epidermal growth factor receptor () mutations in non-small-cell lung cancer (NSCLC) are uncommon mutations. Although the efficacy of second (2G) or third generation (3G) tyrosine kinase inhibitors (EGFR-TKIs) in the patients with uncommon mutation has been proven, further studies are warranted to define the optimal treatment approach for uncommon mutation-positive NSCLC. This study retrospectively investigated the treatment patterns and outcomes of patients with uncommon mutation-positive NSCLC from January 2011 to December 2019 at the Samsung Medical Center, Seoul, Korea. During the study, 2121 patients with mutation-positive NSCLC received first-generation (1G, gefitinib or erlotinib) or 2G EGFR-TKI (afatinib) as the first-line (1L) systemic therapy. Of this, 135 (6.4%) patients harbored uncommon mutations. Of 135, 54 (40%, 54/135) patients had overlapping mutations with major mutations. The objective response rate (ORR) for the 1L EGFR-TKI was 63.3%. The median progression-free survivals (PFSs) were 8.6 months (95% CI: 3.8-13.5), 11.7 months (95% CI: 6.6-16.7), 7.7 months (95% CI: 4.9-17.4), and 5.0 months (95% CI: 3.7-6.1) for major uncommon mutation (G719X, L861Q), compound mutation with major mutation (Del 19 or exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively. The median overall survivals (OSs) were 25.6 months (16.9-34.2), 28.8 (95% CI: 24.4-33.4), 13.5 months (95% CI: 7.4-27.8), and 9.4 months (95% CI: 3.4-10.5) for major uncommon mutation (G719X), compound mutation with major mutation (Del 19 or exon 21 p.L858R), other compound mutation, and other uncommon mutations, respectively. The response rate, median PFS, and OS were 63.3%, 16.3 months (95% CI: 15.6-16.9), and 37.5 months (95% CI: 35.4-39.6) for common mutation-positive NSCLC. After failing 1L -TKI, repeated tissue or liquid biopsy were carried out on 44.9% (35/78) of patients with T790M detected in 10/35 (28.6%) patients. With subsequent 3G -TKI after failing the first-line -TKI, the ORR and PFS for 3G -TKI were 80% and 8.9 months (95% CI: 8.0-9.8). These patients showed a median OS of 34.6 months (95% CI: 29.8-39.4). The ORR, PFS and OS were poorer in patients with uncommon (especially other compound and other uncommon mutation) than those with common mutations. T790M was detected in 28.6% of the uncommon mutation-positive patients for whom prior 1G/2G -TKIs failed and underwent repeat biopsy at the time of progression.
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http://dx.doi.org/10.3390/biology9100326DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600176PMC
October 2020

Utility of positron emission-computed tomography for predicting pathological response in resectable oesophageal squamous cell carcinoma after neoadjuvant chemoradiation.

Eur J Cardiothorac Surg 2020 11;58(5):1019-1026

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Centre, Sungkyunkwan University School of Medicine, Seoul, Korea.

Objectives: For patients with locally advanced oesophageal cancer, improved complete pathological response after neoadjuvant chemoradiation (nCRT) and the detrimental effects on the quality of life related to oesophagectomy have led to the need for a reliable method to select patients who have achieved complete pathological response and do not need surgery. The reliability of 18F-fluorodeoxyglucose positron emission-computed tomography (PET-CT) for predicting the pathological response after nCRT was evaluated.

Methods: Patients with locally advanced oesophageal cancer who were treated with nCRT and oesophagectomy from July 2010 to February 2017 were analysed. On the post-nCRT PET-CT, a complete metabolic response was defined as all tumourous lesions demonstrating maximum standardized uptake value (SUVmax) ≤2.5. To minimize the effect of radiation-induced oesophagitis, complete metabolic response was also defined as no viable lesion distinguishable from the background with diffuse uptake. The sensitivity, specificity, positive predictive value and negative predictive value were analysed for SUVmax, [X]ΔSUVmax and %ΔSUVmax.

Results: A total of 158 patients with oesophageal squamous cell carcinoma were analysed. The rate of complete pathological response was 27.8%, and that of complete metabolic response was 7.6%. The sensitivity, specificity, positive predictive value and negative predictive value based on SUVmax ≤2.5 and visual normalization were 95%, 14%, 74% and 50%, respectively. Analysis for [X]ΔSUVmax and %ΔSUVmax using the optimal cut-off values determined by the receiver operating characteristic curves did not show an improved predictive efficacy.

Conclusions: PET-CT is not a reliable tool for predicting pathological response. Patients diagnosed with resectable oesophageal cancer who underwent neoadjuvant therapy should not be exempt from surgery based on PET-CT results.
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http://dx.doi.org/10.1093/ejcts/ezaa181DOI Listing
November 2020

Diagnostic accuracy of MR imaging of patients with leptomeningeal seeding from lung adenocarcinoma based on 2017 RANO proposal: added value of contrast-enhanced 2D axial T2 FLAIR.

J Neurooncol 2020 Sep 8;149(2):367-372. Epub 2020 Sep 8.

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.

Purpose: We purposed to compare diagnostic accuracy of contrast-enhanced (CE) 3D T1-weighted fast field echo (3D T1-WI), CE 2D spin echo T1-weighted image (2D T1-WI), and CE 2D T2 FLAIR on evaluation of leptomeningeal metastasis(LM) using detailed features suggested in RANO proposal in a homogeneous group with cytology-proven LM.

Methods: Thirty-five lung adenocarcinoma patients with CSF cytology-proven leptomeningeal metastasis were enrolled in this retrospective analysis, who were enrolled in the prospective study (NCT03257124). MR images including CE 3D T1-WI, CE 2D T1-WI, and CE 2D FLAIR were reviewed. Presence of leptomeningeal nodule, leptomeningeal enhancement, and cranial nerve enhancement was evaluated according to the RANO proposal. Diagnostic accuracy of each sequence was compared and added value of CE 2D FLAIR to CE 3D T1-WI was evaluated.

Results: Two patients had unmeasurable small nodules recognized on 3D T1-WI only. Leptomeningeal enhancement was positive in 60%, 60%, and 77.1%, cranial nerve enhancement was positive in 51.4%, 45.7%, and 68.6% of the patients on 3D T1-WI, 2D T1-WI, and 2D FLAIR, respectively. Overall sensitivity for detection of LM was 71.4%, 71.4%, and 82.9% on 3D T1-WI, 2D T1-WI, and 2D FLAIR. When adding 2D FLAIR to 3D T1-WI, overall sensitivity for detection of LM was 82.9%.

Conclusion: 3D T1-WI is the best for identifying leptomeningeal nodules. The sensitivity of 2D FLAIR is the highest for both LNE and CNE. Since both sequences are complementary, it can be helpful to take both sequences. Checking each feature according to the RANO proposal, especially CNE, may help you not to miss LM.
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http://dx.doi.org/10.1007/s11060-020-03617-2DOI Listing
September 2020

Molecular Testing in Lung Cancer: Still Big Gap in Implementation for Real-World Use.

Authors:
Myung-Ju Ahn

J Thorac Oncol 2020 09;15(9):1399-1400

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea. Electronic address:

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http://dx.doi.org/10.1016/j.jtho.2020.06.006DOI Listing
September 2020

Correction to: Hyperprogressive disease and its clinical impact in patients with recurrent and/or metastatic head and neck squamous cell carcinoma treated with immune-checkpoint inhibitors: Korean cancer study group HN 18-12.

J Cancer Res Clin Oncol 2020 Dec;146(12):3371

Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul, 03080, Republic of Korea.

In the original article published, the first name of the author is incorrect. The correct author name is Ji Hyun Park.
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http://dx.doi.org/10.1007/s00432-020-03342-3DOI Listing
December 2020

Are there any ethnic differences in the efficacy and safety of immune checkpoint inhibitors for treatment of lung cancer?

J Thorac Dis 2020 Jul;12(7):3796-3803

Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.

Immunotherapy, especially immune checkpoint inhibitors, has revolutionized the treatment of non-small cell lung cancer. However, data on ethnic differences in response to these treatments are still lacking. We reviewed the currently available clinical data on immune checkpoint inhibitors and analyzed the ethnic difference in terms of treatment efficacies and side effects. Despite different epidemiology, genetic susceptibility and molecular profiles, Asian lung cancer patients demonstrated comparable outcomes to Western patients in terms of response rates and survival benefits. The incidence of immune-related adverse events has been reported with a higher incidence in Japanese patients, but was not consistent across other Asian patient populations, and warrants further investigation.
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http://dx.doi.org/10.21037/jtd.2019.08.29DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7399433PMC
July 2020

Brigatinib Versus Crizotinib in Advanced ALK Inhibitor-Naive ALK-Positive Non-Small Cell Lung Cancer: Second Interim Analysis of the Phase III ALTA-1L Trial.

J Clin Oncol 2020 11 11;38(31):3592-3603. Epub 2020 Aug 11.

Royal Marsden Hospital, London, United Kingdom.

Purpose: Brigatinib, a next-generation anaplastic lymphoma kinase (ALK) inhibitor, demonstrated superior progression-free survival (PFS) and improved health-related quality of life (QoL) versus crizotinib in advanced ALK inhibitor-naive ALK-positive non-small cell lung cancer (NSCLC) at first interim analysis (99 events; median brigatinib follow-up, 11.0 months) in the open-label, phase III ALTA-1L trial (ClinicalTrials.gov identifier: NCT02737501). We report results of the second prespecified interim analysis (150 events).

Methods: Patients with ALK inhibitor-naive advanced ALK-positive NSCLC were randomly assigned 1:1 to brigatinib 180 mg once daily (7-day lead-in at 90 mg once daily) or crizotinib 250 mg twice daily. The primary end point was PFS as assessed by blinded independent review committee (BIRC). Investigator-assessed efficacy, blood samples for pharmacokinetic assessments, and patient-reported outcomes were also collected.

Results: Two hundred seventy-five patients were randomly assigned (brigatinib, n = 137; crizotinib, n = 138). With median follow-up of 24.9 months for brigatinib (150 PFS events), brigatinib showed consistent superiority in BIRC-assessed PFS versus crizotinib (hazard ratio [HR], 0.49 [95% CI, 0.35 to 0.68]; log-rank < .0001; median, 24.0 11.0 months). Investigator-assessed PFS HR was 0.43 (95% CI, 0.31 to 0.61; median, 29.4 9.2 months). No new safety concerns emerged. Brigatinib delayed median time to worsening of global health status/QoL scores compared with crizotinib (HR, 0.70 [95% CI, 0.49 to 1.00]; log-rank = .049). Brigatinib daily area under the plasma concentration-time curve was not a predictor of PFS (HR, 1.005 [95% CI, 0.98 to 1.031]; = .69).

Conclusion: Brigatinib represents a once-daily ALK inhibitor with superior efficacy, tolerability, and QoL over crizotinib, making it a promising first-line treatment of ALK-positive NSCLC.
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http://dx.doi.org/10.1200/JCO.20.00505DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605398PMC
November 2020