|
1
|
Torresan S, Costa J, Zanchetta C, De Marchi L, Rizzato S, Cortiula F. Oligometastatic NSCLC: Current Perspectives and Future Challenges. Curr Oncol 2025; 32:75. [PMID: 39996875 PMCID: PMC11854464 DOI: 10.3390/curroncol32020075] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2024] [Revised: 01/23/2025] [Accepted: 01/26/2025] [Indexed: 02/26/2025] Open
Abstract
Oligometastatic non-small cell lung cancer (NSCLC) represents a separate entity with a different biology and prognosis compared to stage IV NSCLC. Challenges range from the very definition of oligometastatic disease to the timing and techniques of local treatments, and their benefit in prolonging patient survival. Most of the international consensus and guidelines agree on the need for shared criteria, such as appropriate stadiation and even tissue biopsy if needed, in order to select patients that could really benefit from personalised strategies. Multidisciplinary evaluation is crucial in order to define if every lesion is amenable to radical local treatment, which appears to be the most important criterion across different guidelines. A distinction must be made depending on the time of oligo-disease detection, separating de novo oligometastatic disease from oligorecurrence, oligoprogression and oligoresidual disease. These separate entities imply a different biology and prognosis, and treatment strategies consequently must be tailored. Locoregional approaches are therefore often contemplated in order to ensure the best outcome for the patient. In non-oncogene-addicted disease, the advent of immune checkpoint blockers (ICBs) allows physicians to take into consideration consolidative treatments, but timing, technique and subsequent systemic treatment remain open issues. In oncogene-addicted NSCLC, local treatments are nowadays preferably reserved to cases of oligoprogression, but the advent of new, more potent drugs might challenge that. In this review, we summarised the current knowledge, consensuses and data from retrospective and prospective trials, with the aim of shedding some light on the topic and emphasising the unmet clinical need.
Collapse
Affiliation(s)
- Sara Torresan
- Department of Medicine (DME), University of Udine, 33100 Udine, Italy; (S.T.)
- Department of Medical Oncology, IRCCS, Centro di Riferimento Oncologico CRO di Aviano, 33081 Aviano, Italy
| | - Jacopo Costa
- Department of Medicine (DME), University of Udine, 33100 Udine, Italy; (S.T.)
- Department of Oncology, University Hospital of Udine, 33100 Udine, Italy
| | - Carol Zanchetta
- Department of Medicine (DME), University of Udine, 33100 Udine, Italy; (S.T.)
- Department of Oncology, University Hospital of Udine, 33100 Udine, Italy
| | - Lorenzo De Marchi
- Department of Medicine (DME), University of Udine, 33100 Udine, Italy; (S.T.)
- Department of Oncology, University Hospital of Udine, 33100 Udine, Italy
| | - Simona Rizzato
- Department of Oncology, University Hospital of Udine, 33100 Udine, Italy
| | - Francesco Cortiula
- Department of Oncology, University Hospital of Udine, 33100 Udine, Italy
- Department of Respiratory Medicine, Maastricht University Medical Centre, GROW School for Oncology and Reproduction, 6229 ER Maastricht, The Netherlands
| |
Collapse
|
|
2
|
Liao R, Yi G, Shen L, Xiao X, Zeng C, Liu L, Tang H, Huang S, Zhang X, Xu Z, Yang Z, Peng Y. Characterization of the genomic landscape in liver oligometastatic NSCLC. BMC Cancer 2025; 25:93. [PMID: 39819288 PMCID: PMC11737069 DOI: 10.1186/s12885-025-13478-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 01/08/2025] [Indexed: 01/30/2025] Open
Abstract
OBJECTIVES Emerging data have shown that local treatment could provide clinical benefit for non-small cell lung cancer (NSCLC) patients with oligometastasis. Liver metastases have the worst prognosis in advanced NSCLC, but the genomic characteristics of liver oligometastasis remain unclear. The aim of our study was to elucidate the molecular features of liver oligometastatic NSCLC. METHODS Paired liver metastatic tissue samples and peripheral blood from 32 liver oligometastatic NSCLC patients were concurrently collected for comprehensive genomic analysis using next-generation sequencing. RESULTS A total of 206 mutated genes in 32 patients were detected, with a median of 4 mutations per sample. The most frequent alterations (> 10%) in liver oligometastasis were TP53 (72%), EGFR (50%), RB1 (19%) and SMARCA4 (12%). The co-occurrence rate of TP53 and RB1 in our cohort was significantly higher than that in the TCGA-LUAD cohort. Age, APOBEC, homologous recombination deficiency (HRD) and deficient mismatch repair (dMMR) established the mutational signature of liver oligometastatic NSCLC. The median tumor mutation burden (TMB) was 4.8 mutations/Mb. A total of 78.12% patients harbored at least one potentially actionable molecular alteration that may guide further targeted therapy according to the OncoKB evidence. CONCLUSIONS Our study comprehensively delineated the genomic characteristics of liver oligometastatic NSCLC - such findings were helpful to better understand the distinct clinic-biological features of oligometastasis and optimize personalized treatment of this population.
Collapse
Affiliation(s)
- Rongxin Liao
- Department of Cancer Center, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Guangming Yi
- Department of Cancer Center, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
- Department of Oncology, The Third Hospital of Mianyang (Sichuan Mental Health Center), Mianyang, Sichuan, China
| | - Lu Shen
- Geneplus-Beijing, Beijing, China
| | | | - Chuan Zeng
- Department of Cancer Center, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Liangzhong Liu
- Department of Cancer Center, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Hongjun Tang
- Department of Cancer Center, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Shunping Huang
- Department of Cancer Center, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Xiaoyue Zhang
- Department of Cancer Center, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Zaicheng Xu
- Department of Cancer Center, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Zhenzhou Yang
- Department of Cancer Center, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
- Chongqing Clinical Research Center for Geriatrics and Gerontology, Chongqing, China.
- Department of Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
| | - Yuan Peng
- Department of Cancer Center, Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
- Guchengtai Community Health Center of Chengxi District Xining, Xining, Qinghai, China.
- Department of Cancer Center, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, 400010, China.
| |
Collapse
|
|
3
|
Ćeriman Krstić V, Soldatović I, Samardžić N, Gajić M, Kontić M, Reljić A, Savić M, Roksandić Milenković M, Jovanović D. Long-Term Outcomes in Patients with EGFR Positive Lung Adenocarcinoma and Subgroup Analysis Based on Presence of Liver Metastases. Curr Issues Mol Biol 2024; 46:13431-13442. [PMID: 39727929 PMCID: PMC11727537 DOI: 10.3390/cimb46120801] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2024] [Revised: 11/18/2024] [Accepted: 11/20/2024] [Indexed: 12/28/2024] Open
Abstract
Lung cancer represents the most common cause of cancer related death. Patients with non-small cell lung cancer (NSCLC) and liver metastases (LM) have worse prognosis with an overall survival (OS) of three to six months. The aim of this study was to investigate long-term outcomes in patients with EGFR mutated (EGFRmut) lung adenocarcinoma as well as the presence of LM. (A total of 105 patients were included in the analysis). They were divided into two groups based on the presence of LM. OS was 13 months for the whole group and also 13 months for patients with and without LM. The 9-year survival rate for patients with and without LM was 12.5% and 3.4%, respectively. Further, the 9-year survival rate for the whole group of patients was 4.8%. There are few data about survival rates beyond 5 years for patients with locally advanced and metastatic EGFRmut NSCLC, mainly because patients with lung cancer rarely live for such a long time. Regarding patients with liver metastases, the results of our study showed similar outcomes compared to patients without LM. As these patients represent a significant number of patients, we need a wider range of therapeutic options. It might be that combination therapies represent a better therapeutic option.
Collapse
Affiliation(s)
- Vesna Ćeriman Krstić
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (M.K.); (M.S.)
- Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (N.S.); (M.G.)
| | - Ivan Soldatović
- Institute of Medical Statistics, Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia;
| | - Natalija Samardžić
- Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (N.S.); (M.G.)
| | - Milija Gajić
- Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (N.S.); (M.G.)
| | - Milica Kontić
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (M.K.); (M.S.)
- Clinic for Pulmonology, University Clinical Center of Serbia, 11000 Belgrade, Serbia; (N.S.); (M.G.)
| | - Aleksandar Reljić
- Clinic for Ortopedics, University Clinical Center of Serbia, 11000 Belgrade, Serbia;
| | - Milan Savić
- Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia; (M.K.); (M.S.)
- Clinic for Thoracic Surgery, University Clinical Center of Serbia, 11000 Belgrade, Serbia
| | | | | |
Collapse
|
|
4
|
Okuma Y, Shintani Y, Sekine I, Shukuya T, Takayama K, Inoue A, Okamoto I, Kiura K, Yamamoto N, Kawaguchi T, Miyaoka E, Yoshino I, Date H. Efficacy of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Metastatic Non-Small Cell Lung Cancer Patients with Poor Performance Status and Epidermal Growth Factor Receptor Mutations: Findings from the Japanese Lung Cancer Registry Database. Clin Lung Cancer 2024; 25:336-346.e2. [PMID: 38360497 DOI: 10.1016/j.cllc.2024.01.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2023] [Revised: 01/08/2024] [Accepted: 01/20/2024] [Indexed: 02/17/2024]
Abstract
BACKGROUND In advanced non-small cell lung cancer (NSCLC) patients harboring epidermal growth factor receptor (EGFR) mutations, those with impaired performance status (PS) treated with EGFR-tyrosine kinase inhibitors (TKIs) have demonstrated comparable activities to good-PS patients. Due to the limited sample size and inclusion of older adult patients with good PS, these findings may not accurately depict the efficacy of EGFR-TKI in poor-PS patients. We investigated the benefit of EGFR-TKIs in this population and identified relevant prognostic factors. PATIENTS AND METHODS This nationwide prospective registry study included 9872 patients with local or advanced NSCLC. Outcomes were compared between poor- and good-PS patients treated with EGFR-mutated lung cancer therapies. RESULTS Of 9872 NSCLC patients, 1965 (19.9%) had EGFR mutations, with 1846 (93.9%) presenting common EGFR mutations. Poor PS (PS score ≥ 3) was noted in 171 patients (8.7%) and identified as an independent prognostic factor; those with poor PS had a significantly lower 1-year survival rate. The median overall survival (OS) for EGFR-TKI-treated good-PS patients was 31.5 (95% confidence interval, 29.6-33.4) months. Among poor-PS patients with EGFR mutations, 135 (78.9%) of whom were treated with EGFR-TKI had an OS of 15.5 (12.7-18.3) months, while those receiving only supportive care had an OS of 2.5 (1.4-3.6) months (P < .001). Hypoalbuminemia (< 3.5 g/dL), liver metastasis, and uncommon EGFR mutations were associated with poor prognosis. CONCLUSION Poor PS at diagnosis was rare and associated with limited EGFR-TKI efficacy and a dismal prognosis. Liver metastasis and hypoalbuminemia may reduce EGFR-TKI efficacy in these patients.
Collapse
Affiliation(s)
- Yusuke Okuma
- Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan; Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Komagome Hospital, Tokyo, Japan.
| | - Yasushi Shintani
- Department of General Thoracic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Ikuo Sekine
- Department of Medical Oncology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
| | - Takehito Shukuya
- Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
| | - Koichi Takayama
- Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine, Kyoto, Japan
| | - Akira Inoue
- Department of Palliative Medicine, Tohoku University School of Medicine, Miyagi, Japan
| | - Isamu Okamoto
- Department of Respiratory Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Katsuyuki Kiura
- Department of Allergy and Respiratory Medicine, Okayama University Hospital, Okayama, Japan
| | - Nobuyuki Yamamoto
- Department of Internal Medicine III, Wakayama Medical University Hospital, Wakayama, Japan
| | - Tomoya Kawaguchi
- Department of Respiratory Medicine, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Etsuo Miyaoka
- Department of Mathematics, Tokyo University of Science, Tokyo, Japan
| | - Ichiro Yoshino
- Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan
| | - Hiroshi Date
- Department of Thoracic Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| |
Collapse
|
|
5
|
Yang F, Huang Z, Heng J, Li K. Benefit assessment of extended dosing in cancer patients after their withdrawal from clinical trials. Front Pharmacol 2023; 14:1178002. [PMID: 38161690 PMCID: PMC10757887 DOI: 10.3389/fphar.2023.1178002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Accepted: 11/30/2023] [Indexed: 01/03/2024] Open
Abstract
Background: Clinical trials have been widely recognized as an effective treatment approach by physicians and cancer patients alike. Physicians' evaluations suggest that many patients are likely to continue experiencing benefits from extended dosing of investigational new drugs even after withdrawing from clinical trials. Objective: Given the uncertainty surrounding the efficacy and safety of investigational new drugs, it is essential to continually assess the benefits of extended dosing for patients. Methods: The trial group for this study comprised patients who requested extended dosing after withdrawing from clinical trials at Hunan Cancer Hospital between 2016 and 2020. The control group consisted of patients who received conventional treatment and were enrolled in a 1:1 ratio. Follow-up assessments were conducted every 3 months for both groups, and included monitoring of patients' health status, survival time, disease control or remission, treatment modalities received, and medical costs. Results: A total of twenty-three patient pairs were successfully matched for this study. The Ethics Committee approved extended dosing for all patients in the trial group, with an average gap period of 16.48 days between their withdrawal from clinical trials and continuous access to the investigational drugs. The median overall survival for patients after withdrawal from clinical trials was 17.3 months in the extended dosing group and 12.9 months in the control group, with no significant difference observed between the two groups (p > 0.250). The median total cost of treatment after the previous clinical trial was 38,006.76 RMB, of which the median cost of therapeutic drugs for conventional treatment was 15,720 RMB, while extended dosing was provided free of charge. Conclusion: Extended dosing can indeed provide benefits, including survival benefits and economic benefits, to cancer patients after their withdrawal from clinical trials and will clinically present an additional treatment option for patients.
Collapse
Affiliation(s)
- Feng Yang
- Hunan Cancer Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Zhe Huang
- Hunan Cancer Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
- Department of Pathology, Immuno-Oncology Laboratory, School of Basic Medicine, Central South University, Changsha, Hunan, China
| | - Jianfu Heng
- Hunan Cancer Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| | - Kunyan Li
- Hunan Cancer Hospital, Xiangya School of Medicine, Central South University, Changsha, Hunan Province, China
| |
Collapse
|
|
6
|
Huang Y, Kong Y, Wei Z, Ye X. Image-guided thermal ablation for patients with epidermal growth factor receptor-mutant nonsmall cell lung cancer. Asia Pac J Clin Oncol 2023; 19:427-433. [PMID: 36480416 DOI: 10.1111/ajco.13875] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2022] [Accepted: 09/24/2022] [Indexed: 07/20/2023]
Abstract
Nonsmall cell lung cancer (NSCLC) is treated by various therapies such as surgical intervention, radiotherapy, chemotherapy, molecular targeted therapy, and immunotherapy. Currently, molecular targeted therapy, including epidermal growth factor receptor (EGFR) inhibitors and Anaplastic Lymphoma Kinase (ALK) and Kirsten Rat Sarcoma viral Oncogene (KRAS) inhibitors, has received much attention and improved the prognosis of NSCLC. Nevertheless, the terminal point of molecular targeted drugs is resistance. Drug resistance has been classified into oligoprogression and extensive progression based on the tumor lesion progression after drug resistance. There is extensive research demonstrating that local therapy (surgical resection, radiotherapy, and thermal ablation) can prolong the survival of patients with drug resistance. This review is intended to determine the efficacy of image-guided thermal ablation in patients with NSCLC with EGFR mutation.
Collapse
Affiliation(s)
- Yahan Huang
- Department of Oncology, The First Affiliated Hospital of Shandong, First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key, Laboratory of Rheumatic Disease and Translational medicine, Shandong Lung Cancer, Jinan, China
- Shandong First Medical University, Jinan, China
| | - Yongmei Kong
- Department of Oncology, The First Affiliated Hospital of Shandong, First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key, Laboratory of Rheumatic Disease and Translational medicine, Shandong Lung Cancer, Jinan, China
- Shandong First Medical University, Jinan, China
| | - Zhigang Wei
- Department of Oncology, The First Affiliated Hospital of Shandong, First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key, Laboratory of Rheumatic Disease and Translational medicine, Shandong Lung Cancer, Jinan, China
| | - Xin Ye
- Department of Oncology, The First Affiliated Hospital of Shandong, First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Key, Laboratory of Rheumatic Disease and Translational medicine, Shandong Lung Cancer, Jinan, China
| |
Collapse
|
|
7
|
Tam A, Eustace N, Kassardjian A, West H, Williams TM, Amini A. The Emerging Role of Radiotherapy in Oligoprogressive Non-Small Cell Lung Cancer. Surg Oncol Clin N Am 2023; 32:497-514. [PMID: 37182989 DOI: 10.1016/j.soc.2023.02.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/16/2023]
Abstract
Oligoprogressive disease (OPD) is an emerging concept that describes patients who have progression of disease in a limited number of metastatic sites while on systemic therapy. Growing evidence has suggested the integration of local ablative therapy with systemic agents in patients with OPD further improves survival. In oligoprogressive non-small cell lung cancer, stereotactic body radiotherapy may have an important role in the effective local control of selective progressing metastases, which may translate to better patient outcomes. This review explores the treatment paradigm of this subset of patients and provides an update on the current existing literature on this topic.
Collapse
Affiliation(s)
- Andrew Tam
- Department of Radiation Oncology, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, USA
| | - Nicholas Eustace
- Department of Radiation Oncology, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, USA
| | - Ari Kassardjian
- Department of Radiation Oncology, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, USA
| | - Howard West
- Department of Medical Oncology, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, USA
| | - Terence M Williams
- Department of Radiation Oncology, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, USA
| | - Arya Amini
- Department of Radiation Oncology, City of Hope National Medical Center, 1500 East Duarte Road, Duarte, CA, USA.
| |
Collapse
|
|
8
|
Kong Y, Xu H, Huang Y, Wei Z, Ye X. Local thermal ablative therapies for extracranial oligometastatic disease of non-small-cell lung cancer. Asia Pac J Clin Oncol 2023; 19:3-8. [PMID: 35599449 DOI: 10.1111/ajco.13766] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2021] [Revised: 01/21/2022] [Accepted: 01/27/2022] [Indexed: 01/20/2023]
Abstract
Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. Clinically, 40-50% of patients with NSCLC are found to have systemic metastasis at the initial diagnosis. Meanwhile, 30-75% of patients with lung cancer who have undergone radical surgical resection have local recurrence and distant metastases. However, not all distant metastases are multiple, and some are potentially curable. In this study, among the patients with NSCLC having distant organ metastasis, approximately 7% showed extrapulmonary solitary metastasis and remained in this relatively stable state for a long time. This form of metastasis is known as NSCLC oligometastases. This review describes the concept and classification of oligometastases, as well as the local treatment and prognosis of extracranial oligometastases.
Collapse
Affiliation(s)
- Yongmei Kong
- Department of Oncology, The First Affiliated Hospital of Shandong, First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer, Institute, Jinan, China.,Shandong First Medical University, Jinan, China
| | - Hui Xu
- Department of Oncology, The First Affiliated Hospital of Shandong, First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer, Institute, Jinan, China.,Shandong First Medical University, Jinan, China
| | - Yahan Huang
- Department of Oncology, The First Affiliated Hospital of Shandong, First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer, Institute, Jinan, China.,Shandong First Medical University, Jinan, China
| | - Zhigang Wei
- Department of Oncology, The First Affiliated Hospital of Shandong, First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer, Institute, Jinan, China
| | - Xin Ye
- Department of Oncology, The First Affiliated Hospital of Shandong, First Medical University & Shandong Provincial Qianfoshan Hospital, Shandong Key Laboratory of Rheumatic Disease and Translational Medicine, Shandong Lung Cancer, Institute, Jinan, China
| |
Collapse
|
|
9
|
Ghannam Y, Laville A, Kirova Y, Latorzeff I, Levy A, Zhou Y, Bourbonne V. Radiotherapy of the Primary Disease for Synchronous Metastatic Cancer: A Systematic Review. Cancers (Basel) 2022; 14:cancers14235929. [PMID: 36497410 PMCID: PMC9736289 DOI: 10.3390/cancers14235929] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2022] [Revised: 11/24/2022] [Accepted: 11/26/2022] [Indexed: 12/05/2022] Open
Abstract
In the case of synchronous metastatic disease, the local treatment of primary tumors by radiotherapy has long been reserved for palliative indications. The emergence of the concept of oligometastatic and oligopersistent diseases, the advent of new systemic therapies enabling longer overall survival with an enhanced quality of life, a better understanding of the biologic history of metastatic spread, and technical advances in radiation therapy are revolutionizing the management of patients with de novo metastatic cancer. The prognosis of these patients has been markedly improved and many studies have investigated the survival benefits from the local treatment of various primary tumors in cases of advanced disease at the time of diagnosis or in the case of oligopersistence. This article provides an update on the place of irradiation of the primary tumor in cancer with synchronous metastases, and discusses its interest through published or ongoing trials.
Collapse
Affiliation(s)
- Youssef Ghannam
- Radiation Oncology Department, Centre Paul Papin, Institut de Cancérologie de l’Ouest, 49055 Angers, France
- Correspondence: (Y.G.); (V.B.)
| | - Adrien Laville
- Radiation Oncology Department, CHU Amiens-Picardie, 80000 Amiens, France
| | - Youlia Kirova
- Radiation Oncology Department, Institut Curie Paris, CEDEX 05, 75248 Paris, France
| | - Igor Latorzeff
- Radiation Oncology Department, Bât Atrium Clinique Pasteur, 31300 Toulouse, France
| | - Antonin Levy
- Radiation Oncology Department, Gustave Roussy, Université Paris-Saclay, 94805 Villejuif, France
- Faculté de Médecine, Université Paris-Saclay, 94270 Le Kremlin-Bicêtre, France
| | - Yuedan Zhou
- Radiation Oncology Department, CHU Amiens-Picardie, 80000 Amiens, France
| | - Vincent Bourbonne
- Radiation Oncology Department, University Hospital, 29200 Brest, France
- Correspondence: (Y.G.); (V.B.)
| |
Collapse
|
|
10
|
Wang JF, Lu HD, Wang Y, Zhang R, Li X, Wang S. Clinical characteristics and prognosis of non-small cell lung cancer patients with liver metastasis: A population-based study. World J Clin Cases 2022; 10:10882-10895. [PMID: 36338221 PMCID: PMC9631152 DOI: 10.12998/wjcc.v10.i30.10882] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 07/24/2022] [Accepted: 09/16/2022] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND The presence of liver metastasis (LM) is an independent prognostic factor for shorter survival in non-small cell lung cancer (NSCLC) patients. The median overall survival of patients with involvement of the liver is less than 5 mo. At present, identifying prognostic factors and constructing survival prediction nomogram for NSCLC patients with LM (NSCLC-LM) are highly desirable.
AIM To build a forecasting model to predict the survival time of NSCLC-LM patients.
METHODS Data on NSCLC-LM patients were collected from the Surveillance, Epidemiology, and End Results database between 2010 and 2018. Joinpoint analysis was used to estimate the incidence trend of NSCLC-LM. Kaplan-Meier curves were constructed to assess survival time. Cox regression was applied to select the independent prognostic predictors of cancer-specific survival (CSS). A nomogram was established and its prognostic performance was evaluated.
RESULTS The age-adjusted incidence of NSCLC-LM increased from 22.7 per 1000000 in 2010 to 25.2 in 2013, and then declined to 22.1 in 2018. According to the multivariable Cox regression analysis of the training set, age, marital status, sex, race, histological type, T stage, metastatic pattern, and whether the patient received chemotherapy or not were identified as independent prognostic factors for CSS (P < 0.05) and were further used to construct a nomogram. The C-indices of the training and validation sets were 0.726 and 0.722, respectively. The results of decision curve analyses (DCAs) and calibration curves showed that the nomogram was well-discriminated and had great clinical utility.
CONCLUSION We designed a nomogram model and further constructed a novel risk classification system based on easily accessible clinical factors which demonstrated excellent performance to predict the individual CSS of NSCLC-LM patients.
Collapse
Affiliation(s)
- Jun-Feng Wang
- The First Department of Thoracic Oncology, Jilin Province Tumor Hospital, Changchun 130021, Jilin Province, China
| | - Hong-Di Lu
- The First Department of Thoracic Oncology, Jilin Province Tumor Hospital, Changchun 130021, Jilin Province, China
| | - Ying Wang
- The First Department of Thoracic Oncology, Jilin Province Tumor Hospital, Changchun 130021, Jilin Province, China
| | - Rui Zhang
- The First Department of Thoracic Oncology, Jilin Province Tumor Hospital, Changchun 130021, Jilin Province, China
| | - Xiang Li
- Big Data Center for Clinical Research, Jilin Province Tumor Hospital, Changchun 130021, Jilin Province, China
| | - Sheng Wang
- The First Department of Thoracic Oncology, Jilin Province Tumor Hospital, Changchun 130021, Jilin Province, China
| |
Collapse
|
|
11
|
Construction and validation of a nomogram for non small cell lung cancer patients with liver metastases based on a population analysis. Sci Rep 2022; 12:4011. [PMID: 35256719 PMCID: PMC8901853 DOI: 10.1038/s41598-022-07978-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/22/2021] [Accepted: 02/22/2022] [Indexed: 11/12/2022] Open
Abstract
Lung cancer is one of the most common malignancies in the United States, and the common metastatic sites in advanced non-small cell lung cancer (NSCLC) are bone, brain, adrenal gland, and liver, respectively, among which patients with liver metastases have the worst prognosis. We retrospectively analyzed 1963 patients diagnosed with NSCLC combined with liver metastases between 2010 and 2015. Independent prognostic factors for patients with liver metastases from NSCLC were identified by univariate and multivariate Cox regression analysis. Based on this, we developed a nomogram model via R software and evaluated the performance and clinical utility of the model by calibration curve, receiver operating characteristic curves, and decision curve analysis (DCA). The independent prognostic factors for NSCLC patients with liver metastases included age, race, gender, grade, T stage, N stage, brain metastases, bone metastases, surgery, chemotherapy, and tumor size. The area under the curve predicting OS at 6, 9, and 12 months was 0.793, 0.787, and 0.784 in the training cohort, and 0.767, 0.771, and 0.773 in the validation cohort, respectively. Calibration curves of the nomogram showed high agreement between the outcomes predicted by the nomogram and the actual observed outcomes, and the DCA further demonstrated the value of the clinical application of the nomogram. By analyzing the Surveillance, Epidemiology, and End Results database, we established and verified a prognostic nomogram for NSCLC patients with liver metastases, to personalize the prognosis of patients. At the same time, the prognostic nomogram has a satisfactory accuracy and the results are a guide for the development of patient treatment plans.
Collapse
|
|
12
|
Current Management of Oligometastatic Lung Cancer and Future Perspectives: Results of Thermal Ablation as a Local Ablative Therapy. Cancers (Basel) 2021; 13:cancers13205202. [PMID: 34680348 PMCID: PMC8534236 DOI: 10.3390/cancers13205202] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 10/12/2021] [Accepted: 10/13/2021] [Indexed: 12/25/2022] Open
Abstract
A growing body of evidence shows improved overall survival and progression-free survival after thermal ablation in non-small cell lung carcinoma (NSCLC) patients with a limited number of metastases, combined with chemotherapy or tyrosine kinase inhibitors or after local recurrence. Radiofrequency ablation and microwave ablation are the most evaluated modalities, and target tumor size <3 cm (and preferably <2 cm) is a key factor of technical success and efficacy. Although thermal ablation offers some advantages over surgery and radiotherapy in terms of repeatability, safety, and quality of life, optimal management of these patients requires a multidisciplinary approach, and further randomized controlled trials are required to help refine patient selection criteria. In this article, we present a comprehensive review of available thermal ablation modalities and recent results supporting their use in oligometastatic and oligoprogressive NSCLC disease along with their potential future implications in the emerging field of immunotherapy.
Collapse
|
|
13
|
Zhao X, Zhang Y, Gao Z, Han Y. Prognostic value of peripheral naive CD8 + T cells in oligometastatic non-small-cell lung cancer. Future Oncol 2021; 18:55-65. [PMID: 34608815 DOI: 10.2217/fon-2021-0728] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022] Open
Abstract
Aim: This study aimed to investigate the prognostic value of peripheral naive and memory CD8+ and CD4+ T cells and other immune cells in patients with oligometastatic non-small-cell lung cancer (NSCLC) undergoing radiotherapy (RT). Methods: A total of 142 patients with oligometastatic NSCLC treated with RT were enrolled, and their blood samples were collected within 3 days before RT. Immune cells were identified by flow cytometry. Results: Patients with high levels of naive CD8+ T cells had longer overall survival (p = 0.004) and progression-free survival (p = 0.001) than those with low levels of naive CD8+ T cells. Multivariate analyses revealed that naive CD8+ T cells were independently correlated with overall survival (p = 0.019) and progression-free survival (p = 0.024). Conclusion: The results suggest that peripheral naive CD8+ T cells may be an independent prognostic indicator for patients with oligometastatic NSCLC undergoing RT.
Collapse
Affiliation(s)
- Xin Zhao
- Department of Oncology, Hebei Medical University, Shijiazhuang 050017, PR China
| | - Yan Zhang
- Department of Oncology, Hebei Medical University, Shijiazhuang 050017, PR China.,Department of Oncology, Shijiazhuang People's Hospital, Shijiazhuang 050030, PR China
| | - Zhenlin Gao
- Department of Oncology, Shijiazhuang People's Hospital, Shijiazhuang 050030, PR China
| | - Yaguang Han
- Department of Oncology, Shijiazhuang People's Hospital, Shijiazhuang 050030, PR China
| |
Collapse
|
|
14
|
Tjong MC, Louie AV, Iyengar P, Solomon BJ, Palma DA, Siva S. Local ablative therapies in oligometastatic NSCLC-upfront or outback?-a narrative review. Transl Lung Cancer Res 2021; 10:3446-3456. [PMID: 34430379 PMCID: PMC8350079 DOI: 10.21037/tlcr-20-994] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 03/17/2021] [Indexed: 12/14/2022]
Abstract
Patients with oligometastatic (OM) non-small cell lung cancer (NSCLC) have favorable outcomes compared to patients presenting with diffuse metastatic disease. Recent randomized trials have demonstrated safety and efficacy signals for local ablative therapies with radiotherapy, surgery, or radiofrequency ablation for OM-NSCLC patients alongside systemic therapies. However, it remains unclear whether local ablative therapy (LAT) should be offered either upfront preceding systemic therapies or following initial systemic therapies as local consolidative therapy (LCT). Establishing optimal timing of RT and systemic therapy combinations is essential to maximize efficacy while maintaining safety. Most published randomized trial evidence surrounding the benefits of LAT and systemic therapies were generated from OM-NSCLC patients receiving cytotoxic chemotherapy agents. With increasing use of novel agents such as targeted therapies (i.e., tyrosine kinase inhibitors) and immune checkpoint inhibitors in management of metastatic NSCLC patients, LAT timing may need to be modulated based on the use of specific agents. This narrative review will discuss the current evidence on either upfront LAT or LCT for OM-NSCLC based on published trials and cohort studies. We briefly explored the possible biological mechanisms of the potential clinical advantages of either approach. This review also summarized the ongoing trials incorporating both upfront LAT and LCT, and considerations for future LAT strategies.
Collapse
Affiliation(s)
- Michael C Tjong
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Alexander V Louie
- Department of Radiation Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Puneeth Iyengar
- Department of Radiation Oncology, Harold C. Simmons Comprehensive Cancer Center at the University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Benjamin J Solomon
- Division of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| | - David A Palma
- Department of Radiation Oncology, London Health Sciences Centre, London, Ontario, Canada
| | - Shankar Siva
- Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia
| |
Collapse
|
|
15
|
Biomarkers of Targeted Therapy and Immuno-Oncology in Cancers Metastatic to the Breast. Appl Immunohistochem Mol Morphol 2021; 28:661-668. [PMID: 31517642 PMCID: PMC7664953 DOI: 10.1097/pai.0000000000000808] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
The breast is a rare site for metastases, and their molecular characteristics have not been studied yet. Intrinsic molecular genetics, cancer characteristics, and breast tissue immune responses in diverse metastases to the breast have not been previously studied. We identified 64 patients with cancers metastatic to the breast: 51 carcinomas and 13 melanomas. Programmed death ligand 1 (PD-L1), steroid receptors, and HER2/neu expressions were evaluated using immunohistochemistry. Gene sequencing, copy number alterations, microsatellite instability, and tumor mutational burden were performed using next-generation sequencing platforms. The 3 most common primary sites for metastatic carcinomas were lung (37%), ovary (29%), and fallopian tubes/peritoneum (14%). TP53 mutations were commonly (50%) observed among the carcinoma cases, while other mutations were characteristic for the primary cancers (VHL in renal, BRCA1 in the fallopian tube, and BRAF in melanomas). High tumor mutational burden was detected in 5/14 carcinomas and 3/7 melanomas. Tumor cell PD-L1 expression was detected in 6 carcinomas, but not in any of the melanomas, whereas immune cells' expression of PD-L1 was seen in 17 carcinomas and 6 melanomas. Estrogen receptor status was positive in 13/49 carcinomas including 12 adenocarcinomas originating from the ovary and fallopian tube or peritoneum and 1 duodenal neuroendocrine carcinoma. No carcinoma was HER2/neu positive. Intrinsic genetic characteristics of the metastases to the breast followed the pattern commonly seen in primary tumors. Biomarkers of potential benefit to immune checkpoint inhibition therapy were limited to PD-L1-positive non-small cell lung cancer. No common characteristics of the heterogeneous group of tumor metastases to this organ were identified.
Collapse
|
|
16
|
Li K, Cao X, Ai B, Xiao H, Huang Q, Zhang Z, Chu Q, Zhang L, Dai X, Liao Y. Salvage surgery following downstaging of advanced non-small cell lung cancer by targeted therapy. Thorac Cancer 2021; 12:2161-2169. [PMID: 34128318 PMCID: PMC8327695 DOI: 10.1111/1759-7714.14044] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 05/11/2021] [Accepted: 05/14/2021] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Advanced non-small cell lung cancer (NSCLC) accounts for a high proportion of lung cancer cases. Targeted therapy improve the survival in these patients, but acquired drug resistance will inevitably occur. If tumor downstaging is achieved after targeted therapy, could surgical resection before drug resistance improve clinical benefits for patients with advanced NSCLC? Here, we conducted a clinical trial showing that for patients with advanced driver gene mutant NSCLC who did not progress after targeted therapy, salvage surgery (SS) could improve progression-free survival (PFS). Herein, we retrospectively reviewed our former clinical trial and thoracic cancer database in our medical institutions. METHODS We identified patients with advanced driver gene mutant NSCLC treated with targeted therapy plus SS or targeted therapy alone in our former clinical trial and our thoracic cancer database from July 2016 to July 2019. PFS was compared between the targeted therapy plus SS group and the targeted therapy only group using the log-rank test. RESULTS We identified 73 patients with driver gene mutant NSCLC who were treated with targeted therapy and 18 treated with targeted therapy plus SS.Among the 18 patients treated with targeted therapy plus SS, there were no obvious perioperative complications and deaths. Targeted therapy followed by SS resulted in a significantly longer PFS compared with targeted therapy alone (23.4 months VS 12.9 months, p = 0.0004). CONCLUSIONS Salvage surgery after tumor downstaging is a promising therapeutic strategy for some patients with advanced (stage IIIB-IV) NSCLC and may offer a new therapeutic option for multidisciplinary comprehensive treatment of lung cancer.
Collapse
Affiliation(s)
- Kuo Li
- Department of Thoracic Surgery, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Xiaonian Cao
- Department of Thoracic Surgery, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Bo Ai
- Department of Thoracic Surgery, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Han Xiao
- Department of Thoracic Surgery, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Quanfu Huang
- Department of Thoracic Surgery, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Zheng Zhang
- Department of Thoracic SurgeryThe Affliated Yantai Yuhuangding Hospital of Qingdao UniversityYantaiChina
| | - Qian Chu
- Department of Oncology, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Li Zhang
- Department of Oncology, Tongji Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Xiaofang Dai
- Department of Oncology, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| | - Yongde Liao
- Department of Thoracic Surgery, Union Hospital, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
| |
Collapse
|
|
17
|
Fallet V, Matton L, Schernberg A, Canellas A, Cornelis FH, Cadranel J. Local ablative therapy in oncogenic-driven oligometastatic non-small cell lung cancer: present and ongoing strategies-a narrative review. Transl Lung Cancer Res 2021; 10:3457-3472. [PMID: 34430380 PMCID: PMC8350076 DOI: 10.21037/tlcr-20-1152] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2020] [Accepted: 04/02/2021] [Indexed: 01/09/2023]
Abstract
Oligometastatic (OM) disease is defined by a low metastatic tumor spread. OM non-small cell lung cancer (NSCLC) treatment aims to improve the patient's prognosis and quality of life, in an attempt-to-cure objective. Oncogenic-driven metastatic NSCLC accounts for about 20-25% of NSCLCs, with an ever-increasing number of potentially druggable molecular alterations. Due to specific targeted therapy, the care and prognosis of mutated NSCLC is quite different from non-oncogenic-driven NSCLC. However, OM-NSCLC treatment guidelines do not specifically discuss oncogenic-driven OM-NSCLC patients. We conducted a narrative review regarding retrospective and prospective studies published from inception to May 2020 dealing with oncogenic-driven OM-NSCLC in order to: (I) describe the specific patterns of metastatic spread of oncogenic-driven NSCLC (i.e., bone and pleural tropism in EGFR mutated NSCLC and serous and brain metastases in ALK NSCLC); (II) review the low level of current evidence for local ablative therapy (LAT) strategies in patients with oncogenic-driven OM-NSCLC, focusing on the benefit/risk of tyrosine kinase inhibitors (TKI) and LATs combination and (III) present strategies to help to select the best candidate for an attempt-to-cure approach. Finally, the optimal strategy may be to introduce a targeted therapy, then treat all tumor sites with LAT, and finally continue TKI for unknown prolonged duration in an attempt to prolong progression free survival in most patients, improve overall survival for some patients, and potentially lead to a cancer cure for a few patients.
Collapse
Affiliation(s)
- Vincent Fallet
- Department of Pneumology and Thoracic Oncology, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon and GRC 4, Theranoscan, Sorbonne Université, Paris, France
| | - Lise Matton
- Department of Pneumology and Thoracic Oncology, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon and GRC 4, Theranoscan, Sorbonne Université, Paris, France
| | - Antoine Schernberg
- Department of Radiation Oncology, DMU Orphé, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Sorbonne Université, Paris, France
| | - Anthony Canellas
- Department of Pneumology and Thoracic Oncology, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon and GRC 4, Theranoscan, Sorbonne Université, Paris, France
| | - François H. Cornelis
- Department of Interventional Radiology and Oncology, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon, Sorbonne Université, Paris, France
| | - Jacques Cadranel
- Department of Pneumology and Thoracic Oncology, Assistance Publique-Hôpitaux de Paris, Hôpital Tenon and GRC 4, Theranoscan, Sorbonne Université, Paris, France
| |
Collapse
|
|
18
|
Lim JU. Management of Oligometastasis and Oligoprogression in Patients with Epidermal Growth Factor Receptor Mutation-Positive NSCLC in the Era of Third-Generation Tyrosine Kinase Inhibitors. Clin Lung Cancer 2021; 22:e786-e792. [PMID: 33849807 DOI: 10.1016/j.cllc.2021.03.004] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2021] [Revised: 03/08/2021] [Accepted: 03/10/2021] [Indexed: 12/24/2022]
Abstract
This review covers the importance of local consolidative therapy (LCT) in patients with epidermal growth factor receptor (EGFR) mutation-positive with oligometastatic and oligoprogressive non-small-cell lung cancer (NSCLC). With the advent of third-generation EGFR tyrosine kinase inhibitors, a more updated review is necessary. We review the efficacy of LCT, pathophysiological background, and treatment modalities other than radiotherapy. In addition, we also discussed when and how LCT should be applied to patients with oligometastatic and oligoprogressive NSCLC.
Collapse
Affiliation(s)
- Jeong Uk Lim
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
| |
Collapse
|
|
19
|
Xu Y, Li H, Fan Y. Progression Patterns, Treatment, and Prognosis Beyond Resistance of Responders to Immunotherapy in Advanced Non-Small Cell Lung Cancer. Front Oncol 2021; 11:642883. [PMID: 33747966 PMCID: PMC7973268 DOI: 10.3389/fonc.2021.642883] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2020] [Accepted: 01/19/2021] [Indexed: 12/26/2022] Open
Abstract
Introduction Immune checkpoint inhibitors (ICIs) have changed the management of non-small cell lung cancer (NSCLC). However, resistance is inevitable. The disease progression patterns, sequential treatment, and prognosis beyond ICI resistance are not completely understood. Methods We retrospectively analyzed stage IV NSCLC patients who underwent ICI treatment at Zhejiang Cancer Hospital between January 2016 and January 2020 and who suffered disease progression after at least stable disease on immunotherapy for more than 3 months (at least two cycles). Oligoprogression and systematic progression were defined as previous reports. The main outcome measures were progression-free survival (PFS), second PFS (PFS2), and overall survival (OS). Survival curves were plotted using the Kaplan-Meier method. The Cox proportional hazards model was used for multivariate analysis. Results Totally 1,014 NSCLC patients were administered immunotherapy. Of them, 208 NSCLC patients were included in this retrospective study. The estimated PFS, PFS2 and OS were 6.3 months (95% CI 5.6–7.0 months), 10.7 months (95% CI 10.1–12.7 months), and 21.4 months (95% CI 20.6–26.4 months), respectively. After resistance, 55.3% (N = 115) patients developed oligoprogression, and 44.7% (N = 93) systemic progression. For patients with systemic progression, chemotherapy (N = 35, 37.6%), best supportive care (N = 30, 32.3%), and antiangiogenic therapy alone (N = 11, 11.8%) were the major strategies. A combination of local radiotherapy (N = 38, 33.0%) with continued ICIs was the most common treatment used in oligoprogression group, followed by continued immunotherapy with antiangiogenic therapy (N = 19, 16.5%) and local radiotherapy only (N = 17, 14.9%). For patients with oligoprogression, continued immunotherapy plus local radiotherapy can lead to a significantly longer PFS2 (12.9 vs. 10.0 months; p = 0.006) and OS (26.3 vs. 18.5 months, p = 0.001). The PFS2 and OS of patients with oligoprogression were superior to those of patients with systemic progression (PFS2: 13.1 vs. 10.0 months, p = 0.001; OS: 25.8 vs. 19.1 months, p = 0.003). Conclusions The major progression pattern after acquired resistance from immunotherapy is oligoprogression. Local radiotherapy with continued immunotherapy beyond oligoprogression in responders was feasible and led to prolonged PFS2 and OS in advanced NSCLC patients.
Collapse
Affiliation(s)
- Yanjun Xu
- Department of Medical Thoracic Oncology, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Hangzhou, China
| | - Hui Li
- Department of Medical Thoracic Oncology, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Hangzhou, China
| | - Yun Fan
- Department of Medical Thoracic Oncology, Cancer Hospital of University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Institute of Cancer Research and Basic Medical Sciences of Chinese Academy of Sciences, Hangzhou, China
| |
Collapse
|
|
20
|
Zhou Y, Yu F, Zhao Y, Zeng Y, Yang X, Chu L, Chu X, Li Y, Zou L, Guo T, Zhu Z, Ni J. A narrative review of evolving roles of radiotherapy in advanced non-small cell lung cancer: from palliative care to active player. Transl Lung Cancer Res 2021; 9:2479-2493. [PMID: 33489808 PMCID: PMC7815368 DOI: 10.21037/tlcr-20-1145] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Radiotherapy, along with other loco-regional interventions, is conventionally utilized as a palliative approach to alleviate symptoms and mitigate oncological emergencies in advanced non-small cell lung cancer (NSCLC). Thanks to the ongoing improvement of medical treatments in the last decade, such as targeted therapy and immunotherapy, the survival of patients with advanced NSCLC has been considerably prolonged, making it feasible and clinically beneficial for radiotherapy to play a more active role in highly selected subpopulations. In this review, we will focus on the evolving roles of radiotherapy in advanced NSCLC. First of all, among patients who are initially unable to tolerate aggressive treatment due to severe symptoms caused by metastases and/or tumor emergencies, timely radiotherapy could significantly improve their performance status (PS) and general condition, thus giving them a chance for intensive treatment and prolonged survival. The efficacy, potential candidates, and optimal dose-fractionation regimens of radiotherapy in this clinical scenario will be discussed. Additionally, radiotherapy can play a curative role as a concurrent therapy, consolidation therapy, and salvage therapy for patients with oligo-metastatic, oligo-residual, and oligo-progressive disease, respectively. Accumulating evidence from recent clinical trials, basic research, and translational investigations regarding the potentially curative roles of radiotherapy in NSCLC patients with oligo-metastatic disease will be summarized. Moreover, with the advent of various small molecular tyrosine kinase inhibitors (TKIs), the treatment efficacy and overall survival of oncogene-addicted NSCLC with brain metastases have been significantly improved, and the clinical value and optimal timing of cranial radiotherapy have become topics of much debate. Finally, synergistic antitumor interactions between radiotherapy and immunotherapy have been repeatedly demonstrated. Thus, the immune sensitizing role of radiotherapy in advanced NSCLC is also highlighted in this review.
Collapse
Affiliation(s)
- Yue Zhou
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Fan Yu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yang Zhao
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ya Zeng
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xi Yang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Li Chu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Xiao Chu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yida Li
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Liqing Zou
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Tiantian Guo
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Zhengfei Zhu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.,Institute of Thoracic Oncology, Fudan University, Shanghai, China
| | - Jianjiao Ni
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| |
Collapse
|
|
21
|
Zhao Y, Zhang X, Zhao H, Gong T, Li J, Tsauo J, Li X. Systemic Therapy Plus Thermal Ablation Versus Systemic Therapy Alone for Oligometastatic Liver Metastases from Non-small Cell Lung Cancer. Cardiovasc Intervent Radiol 2020; 43:1285-1293. [PMID: 32236671 DOI: 10.1007/s00270-020-02456-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2020] [Accepted: 03/12/2020] [Indexed: 12/24/2022]
Abstract
PURPOSE This study assessed and compared the efficacy and long-term outcomes of systemic therapy plus image-guided thermal ablation versus systemic therapy alone for oligometastatic liver metastases (LMs) from non-small cell lung cancer (NSCLC). MATERIALS AND METHODS This retrospective study was approved by the institutional review board. Written informed consent was waived due to the retrospective design. From November 2012 to December 2017, 61 patients (mean age 59.0 years; 35 males) with oligometastatic LMs from NSCLC (≤ 5 metastatic lesions) who received systemic therapy with (n = 21, group A) or without (n = 40, group B) thermal ablation were analyzed. Progression-free survival (PFS) and overall survival (OS) were estimated by Kaplan-Meier curves. RESULTS The demographic and clinical characteristics were not significantly different between the groups (all P ≥ .05). In total, 28 LMs were entirely ablated, rendering a technical success rate of 100%, without major complications. The overall 6-month response rate was significantly higher in group A than in group B [57.1% (12/21) vs. 26.3% (10/38); P = .026]. The median PFS in group A was significantly longer than in group B [11.0 (95% CI 7.9-16.2) months vs. 5.2 (95% CI 3.7-7.9) months; P = .001]. However, the median OS was not significantly different [27.7 (95% CI 20.6-44.4) months vs. 17.7 (95% CI 14.5-27.5) months; P = .152]. CONCLUSION Systemic therapy plus thermal ablation may prolong PFS but not OS in oligometastatic LMs from NSCLC.
Collapse
Affiliation(s)
- Yanqing Zhao
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli 17#, Chaoyang District, Beijing, 100021, China
| | - Xiaowu Zhang
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli 17#, Chaoyang District, Beijing, 100021, China
| | - He Zhao
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli 17#, Chaoyang District, Beijing, 100021, China
| | - Tao Gong
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli 17#, Chaoyang District, Beijing, 100021, China
| | - Jingui Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli 17#, Chaoyang District, Beijing, 100021, China
| | - Jiaywei Tsauo
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli 17#, Chaoyang District, Beijing, 100021, China.
| | - Xiao Li
- Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Panjiayuan Nanli 17#, Chaoyang District, Beijing, 100021, China.
| |
Collapse
|
|
22
|
Lan B, Abudureheiyimu N, Zhang J, Wang C, Jiang S, Wang J, Ma F, Luo Y, Chen S, Xu B, Fan Y. Clinical features and prognostic factors for extracranial oligometastatic breast cancer in China. Int J Cancer 2020; 147:3199-3205. [PMID: 32535918 DOI: 10.1002/ijc.33152] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 05/26/2020] [Accepted: 06/03/2020] [Indexed: 12/17/2022]
Abstract
Evidence of an oligometastatic state in metastatic breast cancer (MBC) is relatively limited. The aim of our study was to investigate the clinical features and prognostic factors for extracranial oligometastatic breast cancer and to identify the best treatment approaches in this select population. Fifty postoperative inpatients diagnosed with extracranial oligometastatic breast cancer at the National Cancer Center in China between 2009 and 2014 were consecutively enrolled. Oligometastatic breast cancer was defined as MBC with three or fewer metastatic lesions confined to one organ; de novo Stage IV disease and local-regional recurrence were excluded. The median progression-free survival (PFS) and overall survival (OS) times were 15.2 and 78.9 months, respectively, and the 2-year PFS and 5-year OS rates were 40% and 58%, respectively. First-line treatment approach with standard systemic treatment + surgical resection for all metastatic lesions was an independent prognostic factor for prolonged PFS (hazard ratio = 0.32; 95% confidence interval [CI], 0.14-0.73; P = .006) and OS (hazard ratio = 0.35; 95% CI, 0.14-0.86; P = .022). Subgroup analysis showed that patients with a disease-free interval (DFI) ≥24 months, one metastatic lesion or the hormone receptor (HR) + subtype were more likely to get benefit from resection. Patients with oligometastatic breast cancer have a relatively good prognosis. Surgical resection for metastatic lesions could significantly improve PFS and OS. Further prospective research is warranted to confirm the results and to develop biomarkers for better patient selection.
Collapse
Affiliation(s)
- Bo Lan
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Nilupai Abudureheiyimu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jingyi Zhang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chenyu Wang
- Department of Internal Medicine, Peking Union Medical College Hospital, Beijing, China
| | - Shiyu Jiang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiayu Wang
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Fei Ma
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yang Luo
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shanshan Chen
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Binghe Xu
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ying Fan
- Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
23
|
Haussmann J, Matuschek C, Bölke E, Orth K, Ghadjar P, Budach W. The Role of Local Treatment in Oligometastatic and Oligoprogressive Cancer. DEUTSCHES ARZTEBLATT INTERNATIONAL 2020; 116:849-856. [PMID: 31931952 DOI: 10.3238/arztebl.2019.0849] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/09/2019] [Revised: 05/09/2019] [Accepted: 09/23/2019] [Indexed: 12/14/2022]
Abstract
BACKGROUND Systemic treatment is standard for most types of cancer with disseminated metastases. The role of local treatment (LT) of individual tumor foci in patients with oligometastatic disease is unclear and the object of current scientific studies. METHODS This review is based on pertinent publications retrieved by a selective search in PubMed. RESULTS Four randomized trials have shown that radical local treatment confers an advantage with respect to overall survival (OS), compared to systemic treatment alone, in patients with oligometastatic disease. In patients with synchronous metastases and a stable primary tumor, LT prolongs the median overall survival by approximately two years. A single randomized trial for oligometastatic small-cell lung cancer did not show any prolongation of overall survival. Local treatment increased the frequency of grade III side effects by approximately 10%. CONCLUSION Although local treatment already has a place in many guidelines on the basis of the findings of a small number of prospective and retrospective studies, a option of local treatment should be considered by an interdisciplinary tumor board individually for suitable patients.
Collapse
Affiliation(s)
- Jan Haussmann
- Department of Radiation Oncology, Düsseldorf University Hospital, Heinrich-Heine-Universität Düsseldorf; Goslar: Prof. Dr. med. Klaus Orth (formerly: Department of General, Visceral and Thoracic Surgery, Asklepios Harzkliniken Goslar); Department of Radiation Oncology and Radiotherapy, Charité-Universitätsmedizin Berlin
| | | | | | | | | | | |
Collapse
|
|
24
|
Passiglia F, Pilotto S, Facchinetti F, Bertolaccini L, Del Re M, Ferrara R, Franchina T, Malapelle U, Menis J, Passaro A, Ramella S, Rossi G, Trisolini R, Novello S. Treatment of advanced non-small-cell lung cancer: The 2019 AIOM (Italian Association of Medical Oncology) clinical practice guidelines. Crit Rev Oncol Hematol 2020; 146:102858. [PMID: 31918343 DOI: 10.1016/j.critrevonc.2019.102858] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Accepted: 12/03/2019] [Indexed: 01/10/2023] Open
Abstract
The Italian Association of Medical Oncology (AIOM) has developed clinical practice guidelines for the treatment of patients with advanced non-small cell lung cancer (NSCLC). In the current paper a panel of AIOM experts in the field of thoracic malignancies discussed the available scientific evidences, with the final aim of providing a summary of clinical recommendations, which may guide physicians in their current practice.
Collapse
Affiliation(s)
- F Passiglia
- Department of Oncology, University of Turin, San Luigi Hospital, Orbassano (TO), Italy
| | - S Pilotto
- U.O.C. Oncology, University of Verona, Azienda Ospedaliera Universitaria Integrata, Verona, Italy
| | - F Facchinetti
- INSERM U981, Gustave Roussy Cancer Campus, Université Paris Saclay, Villejuif, France
| | - L Bertolaccini
- Division of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - M Del Re
- Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Italy
| | - R Ferrara
- Medical Oncology, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
| | - T Franchina
- Department of Human Pathology "G. Barresi", University of Messina, Italy
| | - U Malapelle
- Department of Public Health, University of Naples "Federico II", Naples, Italy
| | - J Menis
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Medical Oncology Department, Istituto Oncologico Veneto IRCCS, Padova, Italy
| | - A Passaro
- Division of Thoracic Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - S Ramella
- Radiotherapy Unit, Campus Bio-Medico University, Rome, Italy
| | - G Rossi
- Pathologic Anatomy, Azienda USL della Romagna, S. Maria delle Croci Hospital of Ravenna and Degli Infermi Hospital of Rimini, Italy
| | - R Trisolini
- Interventional Pulmonology Unit, Policlinico S. Orsola-Malpighi, Bologna, Italy
| | - S Novello
- Department of Oncology, University of Turin, San Luigi Hospital, Orbassano (TO), Italy.
| |
Collapse
|
|
25
|
Ni Y, Ye X, Yang X, Huang G, Li W, Wang J, Han X, Wei Z, Meng M. Microwave ablation as local consolidative therapy for patients with extracranial oligometastatic EGFR-mutant non-small cell lung cancer without progression after first-line EGFR-TKIs treatment. J Cancer Res Clin Oncol 2020; 146:197-203. [PMID: 31599340 DOI: 10.1007/s00432-019-03043-6] [Citation(s) in RCA: 30] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2019] [Accepted: 09/30/2019] [Indexed: 12/18/2022]
Abstract
OBJECTIVES Evidence from multiple clinical trials showed that local consolidative therapy (LCT) improved survival in oligometastatic non-small cell lung cancer (NSCLC) patients. In the present study, we aim to explore the potential role of microwave ablation (MWA) as LCT for epidermal growth factor receptor (EGFR)-mutant advanced NSCLC patients with extracranial oligometastasis. MATERIALS AND METHODS From January 2015 to December 2018, a total of 86 EGFR-mutant stage IIIB or IV NSCLC patients with extracranial oligometastasis were enrolled for retrospective analysis. MWA was used as LCT for all oligometastatic lesions and/or primary tumors in 34 patients without progression after first-line EGFR-TKIs therapy (consolidation group), while the other 52 patients received only TKIs until disease progression (monotherapy group). We calculated and compared the progression-free survival (PFS) and overall survival (OS) of the two groups. RESULTS AND CONCLUSION Patients with MWA consolidation therapy had significantly improved PFS (median 16.7 vs. 12.9 months, HR 0.44, 95% CI 0.22-0.88, P = 0.02) and OS (median: 34.8 vs. 22.7 months, HR 0.45, 95% CI 0.24-0.88, P = 0.04) than monotherapy group. MWA for LCT was identified as the independent predictive factor for better PFS (HR 0.46, 95% CI 0.37-0.82, P < 0.01) and OS (HR 0.57, 95% CI 0.33-0.91, P = 0.02). Most toxicities were mild and well tolerated. No patient had to discontinue EGFR-TKIs because of MWA complications. These findings suggest that MWA as local consolidative therapy after first-line EGFR-TKIs treatment leads to better disease control and survival than TKIs monotherapy in EGFR-mutant advanced NSCLC patients with extracranial oligometastasis. MWA as a novel option of LCT might be considered for clinical management of these patients.
Collapse
Affiliation(s)
- Yang Ni
- Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, Shandong, 250021, China
| | - Xin Ye
- Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, Shandong, 250021, China.
| | - Xia Yang
- Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, Shandong, 250021, China
| | - Guanghui Huang
- Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, Shandong, 250021, China
| | - Wenhong Li
- Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, Shandong, 250021, China
| | - Jiao Wang
- Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, Shandong, 250021, China
| | - Xiaoying Han
- Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, Shandong, 250021, China
| | - Zhigang Wei
- Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, Shandong, 250021, China
| | - Min Meng
- Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, 324 Jingwuweiqi Road, Jinan, Shandong, 250021, China
| |
Collapse
|
|
26
|
Zhao Y, Zhang B, Wang S, Qiao R, Xu J, Zhang L, Zhang Y, Han B. Management of Central Nervous System Metastases in Patients With Advanced Anaplastic Lymphoma Kinase-Rearranged Non–Small-Cell Lung Cancer During Crizotinib Treatment. Clin Lung Cancer 2019; 20:e631-e637. [DOI: 10.1016/j.cllc.2019.06.013] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2019] [Revised: 05/16/2019] [Accepted: 06/07/2019] [Indexed: 10/26/2022]
|
|
27
|
Microwave Ablation (MWA) of Pulmonary Neoplasms: Clinical Performance of High-Frequency MWA With Spatial Energy Control Versus Conventional Low-Frequency MWA. AJR Am J Roentgenol 2019; 213:1388-1396. [PMID: 31593520 DOI: 10.2214/ajr.18.19856] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
OBJECTIVE. The objective of our study was to evaluate the clinical performance of a new high-frequency (HF) microwave ablation (MWA) technology with spatial energy control for treatment of lung malignancies in comparison with a conventional low-frequency (LF) MWA technology. MATERIALS AND METHODS. In this retrospective study, 59 consecutive patients (mean age, 58.9 ± 12.6 [SD] years) were treated in 71 sessions using HF spatial-energy-control MWA. Parameters collected were technical success and efficacy, tumor diameter, tumor and ablation volumes, ablation time, output energy, complication rate, 90-day mortality, local tumor progression (LTP), ablative margin size, and ablation zone sphericity. Results were compared with the same parameters retrospectively collected from the last 71 conventional LF-MWA sessions. This group consisted of 56 patients (mean age, 60.3 ± 10.8 years). Statistical comparisons were performed using the Wilcoxon-Mann-Whitney test. RESULTS. Technical success was 98.6% for both technologies; technical efficacy was 97.2% for HF spatial-energy-control MWA and 95.8% for LF-MWA. The 90-day mortality rate was 5.1% (3/59) in the HF spatial-energy-control MWA group and 5.4% (3/56) in the LF-MWA group; for both groups, there were zero intraprocedural deaths. The median ablation time was 8.0 minutes for HF spatial-energy-control MWA and 10.0 minutes for LF-MWA (p < 0.0001). Complications were recorded in 21.1% (15/71) of HF spatial-energy-control MWA sessions and in 31.0% (22/71) of LF-MWA sessions (p = 0.182); of these complications, 4.2% (3/71) were major complications in the HF spatial-energy-control MWA group, and 9.9% (7/71) were major complications in the LF-MWA group. The median deviation from ideal sphericity (1.0) was 0.195 in the HF spatial-energy-control MWA group versus 0.376 in the LF-MWA group (p < 0.0001). Absolute minimal ablative margins per ablation were 7.5 ± 3.6 mm (mean ± SD) in the HF spatial-energy-control MWA group versus 4.2 ± 3.0 mm in the LF-MWA group (p < 0.0001). In the HF spatial-energy-control MWA group, LTP at 12 months was 6.5% (4/62). LTP at 12 months in the LF-MWA group was 12.5% (7/56). Differences in LTP rate (p = 0.137) and time point (p = 0.833) were not significant. CONCLUSION. HF spatial-energy-control MWA technology and conventional LFMWA technology are safe and effective for the treatment of lung malignancies independent of the MWA system used. However, HF spatial-energy-control MWA as an HF and high-energy MWA technique achieves ablation zones that are closer to an ideal sphere and achieves larger ablative margins than LF-MWA (p < 0.0001).
Collapse
|
|
28
|
Xu Y, Huang Z, Lu H, Yu X, Li Y, Li W, Chen J, Chen M, Gong L, Chen K, Qin J, Xu X, Jin Y, Zhao J, Shi X, Han N, Xie F, Zhang P, Xu W, Fan Y. Apatinib in patients with extensive-stage small-cell lung cancer after second-line or third-line chemotherapy: a phase II, single-arm, multicentre, prospective study. Br J Cancer 2019; 121:640-646. [PMID: 31523058 PMCID: PMC6889407 DOI: 10.1038/s41416-019-0583-6] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2019] [Revised: 08/23/2019] [Accepted: 08/30/2019] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND Small-cell lung cancer (SCLC) remains an aggressive cancer with short-term survival due to limited therapeutic options. Apatinib is a small-molecule tyrosine kinase inhibitor that selectively inhibits vascular endothelial growth factor receptor-2. This study aimed to investigate the efficacy and safety of apatinib in patients with extensive-stage (EC) SCLC who had progressed after two or three previous therapies. METHODS Eligible patients were histologically confirmed ES-SCLC after two or three previous treatments, including a platinum-based regimen. Patients received apatinib at an initial dose of 500 mg once daily. The primary endpoint was the objective response rate. RESULTS Forty patients were enrolled. At the data cut-off time (November 15, 2018), the median follow-up was 7.4 months; no patients remained on treatment, and five were still in follow-up. An objective response was achieved in 7 of 40 patients (17.5%) in the intention-to-treat population, and 7 of 38 patients (18.4%) in the per-protocol population. The median progression-free survival and overall survival were 3.0 months and 5·8 months, respectively. The most commonly observed grade 3 or greater treatment-related adverse events were hypertension, hand-foot syndrome, increased L-gamma-glutamyltransferase. CONCLUSIONS Apatinib exhibited efficacy and an acceptable safety profile in previously heavily-treated ES-SCLC patients. Further exploration of apatinib in phase III trials is warranted. TRIAL REGISTRATION NCT02945852.
Collapse
Affiliation(s)
- Yanjun Xu
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China
| | - Zhiyu Huang
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China
| | - Hongyang Lu
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China
| | - Xinming Yu
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China
| | - Yuping Li
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Wenfeng Li
- Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China
| | - Jun Chen
- Department of Radiotherapy and Chemotherapy, Yinzhou People's Hospital, Ningbo, China
| | - Ming Chen
- Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China
| | - Lei Gong
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China
| | - Kaiyan Chen
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China
| | - Jin Qin
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China
| | - Xiaoling Xu
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China
| | - Ying Jin
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China
| | - Jun Zhao
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China
| | - Xun Shi
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China
| | - Na Han
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China
| | - Fajun Xie
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China
| | - Peng Zhang
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China
| | - Weizhen Xu
- Good Clinical Practice Center of Zhejiang Cancer Hospital, Hangzhou, China
| | - Yun Fan
- Department of Medical Thoracic Oncology, Zhejiang Cancer Hospital, No. 1 Banshan East Road, Hangzhou, China. .,Key laboratory on Diagnosis and Treatment Technology on Thoracic Cancer, Zhejiang Cancer Hospital (Zhejiang Cancer Research Institute), Hangzhou, China.
| |
Collapse
|