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Guckenberger M, Opitz I, Dellaporta T, Curioni-Fontecedro A, Frauenfelder T, Ribi K, Cerciello F, Sullivan I, Hendriks L, Dorta M, Callejo A, Aerts J, Addeo A, Dingemans AMC, Pasello G, Provencio M, de Marinis F, Mederos-Alfonso N, Roschitzki-Voser H, Ruepp B, Haberecker M, Kammler R, Dafni U, Peters S, Stahel R. Multimodality treatment in synchronous oligometastatic NSCLC: Analysis of the ETOP CHESS trial. Lung Cancer 2025; 204:108553. [PMID: 40311307 DOI: 10.1016/j.lungcan.2025.108553] [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: 12/05/2024] [Revised: 03/19/2025] [Accepted: 04/20/2025] [Indexed: 05/03/2025]
Abstract
OBJECTIVE To evaluate the addition of immunotherapy and metastasis-directed stereotactic body radiotherapy (SBRT) to induction chemotherapy followed by definitive local therapy of the locoregional primary tumour in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC). METHODS CHESS is a prospective, international, multicentre, single-arm, phase II trial evaluating the efficacy and safety of combined chemotherapy (carboplatin plus paclitaxel), immune checkpoint inhibition (durvalumab) and metastasis-directed SBRT, followed by definitive radiotherapy or surgery of the primary tumour (if no disease progression at the 3-month restaging) and maintenance durvalumab for maximum one year in patients with synchronous oligometastatic NSCLC. The primary endpoint was one-year progression-free survival, aiming to an improvement from 25% to 50%. RESULTS A total of 49 patients were enrolled from 11/2019 to 07/2022. Up to 05/2023, the median follow-up was 22 months. Of 47 patients starting treatment, 10 progressed and 2 died before restaging, while 35 proceeded to definitive therapy of the locoregional primary (11surgery, 24 radiotherapy). Among the first 42 evaluable patients, 14 (33%; ≥17 required) reached one year without progression, and the null hypothesis could not be rejected. The one-year overall survival rate for all patients was 74.9% (95% CI: 60.0%-84.9%). Treatment-related grade ≥ 3 adverse events were reported in 34% of patients, with no grade 5 event. CONCLUSION The CHESS trial did not meet its primary endpoint. However, the favourable safety profile and promising overall survival provided the basis for further intensification of induction systemic therapy (addition of tremelimumab in a subsequent study cohort; CHESS-Cohort 2).
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Affiliation(s)
- Matthias Guckenberger
- University Hospital Zurich, University of Zurich, Department for Radiation Oncology, Zürich, Switzerland
| | - Isabelle Opitz
- University Hospital Zurich, University of Zurich, Department of Thoracic Surgery, Zürich, Switzerland
| | - Tereza Dellaporta
- Frontier Science Foundation-Hellas, ETOP Statistical Office, Athens, Greece
| | - Alessandra Curioni-Fontecedro
- Hôpital Cantonal HFR Fribourg, University of Fribourg, Department of Oncology, Fribourg, Switzerland; Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland
| | - Thomas Frauenfelder
- University Hospital Zurich, University Zurich, Diagnostic and Interventional Radiology, Zürich, Switzerland
| | - Karin Ribi
- ETOP IBCSG Partners Foundation, Coordinating Center, Bern, Switzerland
| | - Ferdinando Cerciello
- Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Switzerland
| | - Ivana Sullivan
- Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; Spanish Lung Cancer Group, (GECP), Barcelona, Spain
| | - Lizza Hendriks
- Maastricht University Medical Center, Department of Pulmonary Diseases, GROW - Research Institute for Oncology and Reproduction, Maastricht, Netherlands
| | - Miriam Dorta
- Spanish Lung Cancer Group, (GECP), Barcelona, Spain; Hospital HM Sanchinarro, Centro Integral Oncología Clara Campal, Madrid, Spain
| | - Ana Callejo
- Spanish Lung Cancer Group, (GECP), Barcelona, Spain; Vall d'Hebron University Hospital, Barcelona, Spain
| | - Joachim Aerts
- Erasmus MC Cancer Institute, University Medical Center, Department of Pulmonary Medicine, Rotterdam, Netherlands
| | - Alfredo Addeo
- Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; University Hospital Geneva (HUG), Department of Oncology, Geneva, Switzerland
| | - Anne-Marie C Dingemans
- Erasmus MC Cancer Institute, University Medical Center, Department of Pulmonary Medicine, Rotterdam, Netherlands
| | - Giulia Pasello
- Oncology 2, Instituto Oncologico Veneto IRCCS, Padova, Italy; Department of Surgery, Oncology and Gastroenterology, University of Padova, Padua, Italy
| | - Mariano Provencio
- Spanish Lung Cancer Group, (GECP), Barcelona, Spain; Hospital Universitario Puerta de Hierro, Madrid, Spain
| | | | - Nuria Mederos-Alfonso
- Swiss Group for Clinical Cancer Research (SAKK), Bern, Switzerland; Centre Hospitalier Universitaire Vaudois (CHUV), Département d'Oncologie, Lausanne, Switzerland
| | | | - Barbara Ruepp
- ETOP IBCSG Partners Foundation, Coordinating Center, Bern, Switzerland
| | - Martina Haberecker
- University Hospital Zurich, Department Pathology and Molecular Pathology, Zürich, Switzerland
| | - Roswitha Kammler
- ETOP IBCSG Partners Foundation, Coordinating Center, Bern, Switzerland
| | - Urania Dafni
- Frontier Science Foundation-Hellas, ETOP Statistical Office, Athens, Greece; National and Kapodistrian University of Athens, Athens, Greece
| | - Solange Peters
- Centre Hospitalier Universitaire Vaudois (CHUV), Département d'Oncologie, Lausanne, Switzerland
| | - Rolf Stahel
- ETOP IBCSG Partners Foundation, Coordinating Center, Bern, Switzerland
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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] [Download PDF] [Figures] [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.
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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
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Tokito T, Yamada K, Ishii H, Takiguchi Y, Saito G, Minato K, Imai H, Tanaka H, Miura S, Watanabe K, Koreeda Y, Ono A, Furuya N, Misumi T, Hayakawa K, Ogo E, Okamoto H. Single-arm multicenter phase II study on aggressive local consolidative therapy in combination with systemic chemotherapy for stage IV non-small cell lung carcinoma with oligometastases: CURE-OLIGO (TORG1529). Radiat Oncol 2025; 20:2. [PMID: 39755666 DOI: 10.1186/s13014-024-02577-5] [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: 08/14/2024] [Accepted: 12/27/2024] [Indexed: 01/06/2025] Open
Abstract
INTRODUCTION Stage IV non-small cell lung carcinoma (NSCLC) with oligometastases is potentially curable by radical treatment. This study aimed to evaluate the efficacy and safety of chemoradiotherapy (CRT) for thoracic disease, including the primary lesion and lymph node metastases, combined with local consolidative therapy (LCT) for oligometastases. METHODS This was a multicenter Phase II trial for patients with Stage IV NSCLC with oligometastases for whom CRT for thoracic disease was feasible. The treatment procedures included CRT containing platinum-doublet for thoracic disease and LCT for oligometastases within 8 weeks of starting or completing CRT. The primary endpoint was the 2-year survival rate. RESULTS We enrolled 19 patients between June 2016 and May 2020. The median age was 68 (range: 51-74) years. Twelve patients had adenocarcinoma, and 6 had squamous cell carcinoma. The metastasis sites included the brain, bone, adrenal gland, lung, and cervical lymph node (n = 9, 7, 2, 1, and 1, respectively). All patients completed CRT concurrently with LCT for all oligometastases. There were 11 partial responses, resulting in a response rate of 58% (95% confidence interval [CI] 33.5-79.7%). Median progression-free survival and overall survival were 8.6 (95% CI 7.0-10.2) and 42.1 (80% CI 13.6-not reached) months, respectively. The 2-year survival rate was 68.4% (80% CI 52.6%-79.9%). Fourteen patients (74%) showed progression with newly observed lesions. There were no severe adverse events, and toxicities were tolerable. CONCLUSION Chemotherapy in combination with aggressive LCT for NSCLC with oligometastases might extend survival and achieve local control. CLINICAL TRIAL REGISTRATION University Hospital Medical Information Network, Japan (protocol identification number: UMIN000022431, first registration date: 01/JUN/2016).
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Affiliation(s)
- Takaaki Tokito
- Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan
| | - Kazuhiko Yamada
- Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan.
- Department of Respiratory Medicine, Shin-Koga Hospital, Temjin-machi, Kurume, Fukuoka, 830-8577, Japan.
| | - Hidenobu Ishii
- Division of Respirology, Neurology, and Rheumatology, Department of Internal Medicine, Kurume University School of Medicine, Kurume, Fukuoka, Japan
| | - Yuichi Takiguchi
- Department of Medical Oncology, Graduate School of Medicine, Chiba University Hospital, Chiba, Japan
| | - Go Saito
- Department of Respirology, Graduate School of Medicine, Chiba University Hospital, Chiba, Japan
| | - Koichi Minato
- Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Gunma, Japan
| | - Hisao Imai
- Division of Respiratory Medicine, Gunma Prefectural Cancer Center, Ota, Gunma, Japan
- Department of Respiratory Medicine, International Medical Center, Saitama Medical University, Hidaka, Saitama, Japan
| | - Hiroshi Tanaka
- Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Niigata, Japan
| | - Satoru Miura
- Department of Internal Medicine, Niigata Cancer Center Hospital, Niigata, Niigata, Japan
| | - Kageaki Watanabe
- Department of Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, Bunkyo-ku, Tokyo, Japan
| | - Yoshifusa Koreeda
- Department of Respiratory Medicine, Minamikyusyu National Hospital, Aira, Kagoshima, Japan
| | - Akira Ono
- Division of Thoracic Oncology, Shizuoka Cancer Center, Sunto-gun, Shizuoka, Japan
| | - Naoki Furuya
- Division of Respiratory Medicine, Department of Internal Medicine, St. Marianna University School of Medicine, Kawasaki, Kanagawa, Japan
| | - Toshihiro Misumi
- Department of Data Science, National Cancer Center Hospital East, Kashiwa, Chiba, Japan
| | - Kazushige Hayakawa
- Department of Radiation Oncology, National Hospital Organization Disaster Medical Center, Tachikawa, Tokyo, Japan
| | - Etsuyo Ogo
- Radiation Oncology Center, Kurume University, Kurume, Fukuoka, Japan
| | - Hiroaki Okamoto
- Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen's Hospital, Yokohama, Kanagawa, Japan
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Sidhu C, Tang C, Scott A, Yamini Ramamurty H, Yagnik L, Morey S, Phillips M, Jacques A, Thomas R. Feasibility, safety and outcomes of stereotactic radiotherapy for ultra-central thoracic oligometastatic disease guided by linear endobronchial ultrasound-inserted fiducials. Radiother Oncol 2024; 201:110547. [PMID: 39332638 DOI: 10.1016/j.radonc.2024.110547] [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: 05/03/2024] [Revised: 09/09/2024] [Accepted: 09/13/2024] [Indexed: 09/29/2024]
Abstract
BACKGROUND & PURPOSE Local treatment of oligometastases has been found to improve survival and prognosis. Stereotactic body radiotherapy (SBRT) has emerged as a treatment option for oligometastases but its use in ultra-central (UC) areas can cause significant toxicity and mortality. Fiducial markers (FM) can be used to improve SBRT accuracy, and can be inserted in the central thorax using linear endobronchial ultrasound (EBUS) bronchoscopy. Outcomes of FM-guided SBRT for UC thoracic oligometastases is unknown. METHODS A single-centre retrospective study investigating the feasibility, safety and outcomes of both linear EBUS-inserted FMs and subsequent FM-guided SBRT for UC-oligometastatic disease. Motion analyses of FMs were also performed. RESULTS Thirty outpatients underwent 32 EBUS-FM insertion procedures with 100 % success, and no major procedural mortality or morbidity. Minor complications were 4.8 % incidence of delayed FM-displacement. UC FM-guided SBRT was completed in 20 patients with 99.9 % fractions delivered. Median SBRT dose delivered was 40 Gy over a median of 8 fractions. Majority of adverse events were Grade 1 and there was no SBRT-related mortality. Local control with SBRT was 95 %, with overall survival at 1-year and 3-years of 90 % and 56.3 % respectively. Median overall survival after SBRT was 43.6 months. FM movements in UC areas were recorded being greatest in the superior-inferior axis. CONCLUSION Combined linear EBUS sampling and FM-insertion in UC thoracic oligometastatic disease is feasible and safe. UC-SBRT to oligometastases using FM guidance was found to have minimal complications and associated with moderate survival up to 3 years post-treatment.
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Affiliation(s)
- Calvin Sidhu
- School of Health Sciences, Edith Cowan University, Joondalup, Australia.
| | - Colin Tang
- School of Health Sciences, Edith Cowan University, Joondalup, Australia; Department of Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Australia
| | - Alison Scott
- Department of Radiation Oncology, Sir Charles Gairdner Hospital, Perth, Australia
| | - Hema Yamini Ramamurty
- Department of Respiratory Medicine, Queen Elizabeth Hospital, Kota Kinabalu, Malaysia
| | - Lokesh Yagnik
- Department of Respiratory Medicine, Fiona Stanley Hospital, Perth, Australia
| | - Sue Morey
- Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia
| | | | - Angela Jacques
- Institute of Health Research, University of Notre Dame, Fremantle, Australia
| | - Rajesh Thomas
- Department of Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia; School of Medicine, University of Western Australia, Perth, Australia; Institute for Respiratory Health, Perth, Australia
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Christ SM, Thiel GW, Heesen P, Roohani S, Mayinger M, Willmann J, Ahmadsei M, Muehlematter UJ, Maurer A, Buchner JA, Peeken JC, Rahman R, Aizer A, Rhun EL, Andratschke N, Weller M, Huellner M, Guckenberger M. Influence of brain metastases on the classification, treatment, and outcome of patients with extracranial oligometastasis: a single-center cross-sectional analysis. Radiat Oncol 2024; 19:148. [PMID: 39465396 PMCID: PMC11514885 DOI: 10.1186/s13014-024-02542-2] [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: 06/10/2024] [Accepted: 10/16/2024] [Indexed: 10/29/2024] Open
Abstract
BACKGROUND AND INTRODUCTION Increasing evidence suggests that a subgroup of patients with oligometastatic cancer might achieve a prolonged disease-free survival through local therapy for all active cancer lesions. Our aims are to investigate the impact of brain metastases on the classification, treatment, and outcome in these patients. MATERIALS AND METHODS We analyzed a total of 7,000 oncological positron emission tomography scans to identify patients with extracranial oligometastatic disease (defined as ≤ 5 intra- or extra-cranial metastases). Concurrent magnetic resonance imaging brain was assessed to quantify intracranial tumor burden. We investigated the impact of brain metastases on oligometastatic disease state, therapeutic approaches, and outcome. Predictors for transitioning from oligo- to polymetastatic states were evaluated using regression analysis. RESULTS A total of 106 patients with extracranial oligometastases and simultaneous brain metastases were identified, primarily originating from skin or lung/pleura cancers (90%, n = 96). Brain metastases caused a transition from an extracranial oligometastatic to a whole-body polymetastatic state in 45% (n = 48) of patients. While oligometastatic patients received systemic therapy (55% vs. 35%) more frequently and radiotherapy for brain metastases was more often prescribed to polymetastatic patients (44% vs. 26%), the therapeutic approach did not differ systematically between both sub-groups. The oligometastatic sub-group had a median overall survival of 28 months compared to 10 months in the polymetastatic sub-group (p < 0.01). CONCLUSION In patients with brain metastases, a low total tumor burden with an oligometastatic disease state remained a significant prognostic factor for overall survival. Presence of brain metastases should therefore not serve as exclusion criterion for clinical trials in the field of oligometastatic disease. Moreover, it underscores the importance of considering a multimodality treatment strategy in oligometastatic cancer patients.
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Affiliation(s)
- Sebastian M Christ
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Rämistrasse 100, Zurich, 8091, Switzerland.
| | | | | | - Siyer Roohani
- Department of Radiation Oncology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Augustenburger Platz 1, 13353, Berlin, Germany
| | - Michael Mayinger
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Rämistrasse 100, Zurich, 8091, Switzerland
| | - Jonas Willmann
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Rämistrasse 100, Zurich, 8091, Switzerland
| | - Maiwand Ahmadsei
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Rämistrasse 100, Zurich, 8091, Switzerland
| | - Urs J Muehlematter
- Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Alexander Maurer
- Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Josef A Buchner
- Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Jan C Peeken
- Department of Radiation Oncology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany
| | - Rifaquat Rahman
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham & Women's Hospital, Boston, MA, USA
| | - Ayal Aizer
- Department of Radiation Oncology, Dana-Farber Cancer Institute, Brigham & Women's Hospital, Boston, MA, USA
| | - Emilie Le Rhun
- Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
- Department of Neurosurgery, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Nicolaus Andratschke
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Rämistrasse 100, Zurich, 8091, Switzerland
| | - Michael Weller
- Department of Neurology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Martin Huellner
- Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Matthias Guckenberger
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Rämistrasse 100, Zurich, 8091, Switzerland
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Xie T, Qiu BM, Luo J, Diao YF, Hu LW, Liu XL, Shen Y. Distant metastasis patterns among lung cancer subtypes and impact of primary tumor resection on survival in metastatic lung cancer using SEER database. Sci Rep 2024; 14:22445. [PMID: 39341901 PMCID: PMC11438988 DOI: 10.1038/s41598-024-73389-6] [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: 04/11/2024] [Accepted: 09/17/2024] [Indexed: 10/01/2024] Open
Abstract
This research aimed to systematically uncover the metastatic characteristics and survival rates of lung cancer subtypes and to evaluate the impact of surgery at the primary tumor site on cancer-specific survival in DM lung cancer. We used the Surveillance, Epidemiology, and End Results (SEER) database (2010-2019) to identify primary lung cancers with DM at presentation (M1). Kaplan-Meier (KM) survival curves were generated and compared utilizing log-rank tests. Cox regression methods were employed to determine hazard ratios (HR) and 95% confidence intervals related to CSS factors. Inverse probability of treatment weighting (IPTW) was applied to reduce bias. We analyzed 77,827 M1 lung cancer cases, with 41.22% having DM at presentation. Bone metastasis was most common in ADC, ASC, SCC, LCC; brain in LCNEC; liver in SCLC. Lung was common in TC + AC and SCC. Long-term survival was best in TC + AC and worst in SCLC (p < 0.001). Male gender, age < 50, primary tumor site (main bronchus, lower lobe), large tumor diameter, ADC/SCLC/SCC pathology, and regional lymph node involvement were significant risk factors for multiorgan metastasis. Age ≥ 50, male, large tumor diameter, positive lymph nodes, and multiorgan metastases were associated with lower CSS. In contrast, radiotherapy, chemotherapy, systemic therapy, and surgery were associated with higher CSS rates. Primary tumor resection improved survival in lung cancer patients (excluding small cell lung cancer, SCLC) with single organ metastases (KM log rank p < 0.001, HR = 0.6165; 95% CI (0.5468-0.6951)), especially in brain (p < 0.001, HR = 0.6467; 95% CI (0.5505-0.7596)) and bone (p = 0.182, HR = 0.6289; p < 0.01), but not in liver or intrapulmonary metastases after IPTW. Significant differences in DM patterns and corresponding survival rates exist among lung cancer subtypes. Primary tumor resection improves survival in lung cancer patients (excluding small cell lung cancer, SCLC) with single organ metastases, with better outcomes in patients with brain and bone metastases, while no significant benefit was seen in patients with liver and intrapulmonary metastases.
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Affiliation(s)
- Tian Xie
- Department of Cardiothoracic Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
- Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, 210093, Jiangsu, China
| | - Bing-Mei Qiu
- Department of Cardiothoracic Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Jing Luo
- Department of Cardiothoracic Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Yi-Fei Diao
- Department of Cardiothoracic Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Li-Wen Hu
- Department of Cardiothoracic Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Xiao-Long Liu
- Department of Cardiothoracic Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - Yi Shen
- Department of Cardiothoracic Surgery, Nanjing Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
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Schmid S, Garcia M, Zhan L, Cheng S, Khan K, Chowdhury M, Sabouhanian A, Herman J, Walia P, Strom E, Brown MC, Patel D, Xu W, Shepherd FA, Sacher AG, Leighl NB, Bradbury PA, Liu G, Shultz D. Outcomes with non-small cell lung cancer and brain-only metastasis. Heliyon 2024; 10:e37082. [PMID: 39296139 PMCID: PMC11408029 DOI: 10.1016/j.heliyon.2024.e37082] [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: 11/08/2023] [Revised: 08/27/2024] [Accepted: 08/27/2024] [Indexed: 09/21/2024] Open
Abstract
Background We evaluated outcomes in non-small cell lung cancer (NSCLC) patients who presented with brain-only metastatic (BOM) disease overall and by EGFR/ALK mutation status. Methods We analyzed clinico-demographic, treatment and survival data for all NSCLC patients who presented to our center between 2014 and 2016 with BOM as their first presentation of metastatic disease. Differences in overall survival (OS) were evaluated using log-rank tests for NSCLC wildtype (NSCLCwt) versus NSCLC with an ALK-rearrangement/EGFR-mutation (NSCLCmut+). Results Of 109 patients with BOM, median age was 68 years; 51 % were female; 69 % Caucasian; 76 % ever-smoker; 76 % adenocarcinoma; and 25 % NSCLCmut+. While 41 patients (38 %) had subsequent brain-only progressive disease (PD), 22 (20 %) developed extracranial metastases. A higher proportion of NSCLCmut+ (vs -wt) subsequently progressed outside the brain (37 % vs 15 %, p = 0.03). Median time-to-first-extracranial-metastases was 8.5 (NSCLCmut+) vs 21.0 months (NSCLCwt; p = 0.23).With 17.7 months median follow-up, median-OS was 15.9 months [95%CI: 11.5-21.3; all patients]; 12.3 [7.4-18.4; NSCLCwt] and 38.9 [21.3-not reached (NR); NSCLCmut+] (p = 0.09). In 33 of 80 patients with de novo BOM, the primary tumor was treated with surgery or radiotherapy. In patients with NSCLCwt, there was no OS benefit associated with local lung tumor treatment (p = 0.68), whereas in NSCLCmut + pts, local lung tumor treatment correlated with greater OS (median-OS NR vs 21.5 months; p = 0.05). Conclusion In patients with NSCLCwt with BOM, we observed a -predominant pattern of brain-only secondary progression, however patients with NSCLCmut + more often progressed extracranially. In patients with NSCLCmut+ and BOM, definitive primary tumor treatment correlated with improved survival.
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Affiliation(s)
- Sabine Schmid
- Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Switzerland
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - Miguel Garcia
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
- Ramon y Cajal University Hospital, Madrid, Spain
| | - Luna Zhan
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - Sierra Cheng
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - Khaleeq Khan
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - Maisha Chowdhury
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - Amir Sabouhanian
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - Joshua Herman
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - Preet Walia
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - Evan Strom
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - M Catherine Brown
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - Devalben Patel
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - Wei Xu
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - Frances A Shepherd
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - Adrian G Sacher
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - Natasha B Leighl
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | | | - Geoffrey Liu
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
| | - David Shultz
- University Health Network, Princess Margaret Cancer Centre, Toronto, Canada
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8
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Rodriguez-Quintero JH, Jindani R, Kamel MK, Zhu R, Vimolratana M, Chudgar NP, Stiles BM. Resection of the Primary Tumor and Survival in Patients with Single-Site Synchronous Oligometastatic Non-Small Cell Lung Cancer: Propensity-Matched Analysis of the National Cancer Database. J Am Coll Surg 2024; 238:1122-1136. [PMID: 38334285 PMCID: PMC11096043 DOI: 10.1097/xcs.0000000000001035] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/10/2024]
Abstract
BACKGROUND Local therapy for the primary tumor is postulated to remove resistant cancer cells as well as immunosuppressive cells from the tumor microenvironment, potentially improving response to systemic therapy (ST). We sought to determine whether resection of the primary tumor was associated with overall survival (OS) in a multicentric cohort of patients with single-site synchronous oligometastatic non-small cell lung cancer. STUDY DESIGN Using the National Cancer Database (2018 to 2020), we evaluated patients with clinical stage IVA disease who received ST and stratified the cohort based on receipt of surgery for the primary tumor (S). We used multivariable and propensity score-matched analysis to study factors associated with S (logistic regression) and OS (Cox regression and Kaplan-Meier), respectively. RESULTS Among 12,215 patients identified, 2.9% (N = 349) underwent S and 97.1% (N = 11,886) ST (chemotherapy or immunotherapy) without surgery. Patients who underwent S were younger, more often White, had higher income levels, were more likely to have private insurance, and were more often treated at an academic facility. Among those who received S, 22.9% (N = 80) also underwent resection of the distant metastatic site. On multivariable analysis, metastasis to bone, N+ disease, and higher T-stages were independently associated with less S. On Cox regression, S and resection of the metastatic site were associated with improved survival (hazard ratio 0.67, 95% CI 0.56 to 0.80 and hazard ratio 0.80, 95% CI 0.72 to 0.88, respectively). After propensity matching, OS was improved in patients undergoing S (median 36.8 vs 20.8 months, log-rank p < 0.001). CONCLUSIONS Advances in ST for non-small cell lung cancer may change the paradigm of eligibility for surgery. This study demonstrates that surgical resection of the primary tumor is associated with improved OS in selected patients with single-site oligometastatic disease.
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Affiliation(s)
- Jorge Humberto Rodriguez-Quintero
- Montefiore Medical Center/ Albert Einstein College of Medicine. Department of Cardiothoracic and Vascular Surgery. 3400 Bainbridge. Bronx, New York. 10467
| | - Rajika Jindani
- Montefiore Medical Center/ Albert Einstein College of Medicine. Department of Cardiothoracic and Vascular Surgery. 3400 Bainbridge. Bronx, New York. 10467
| | - Mohamed K Kamel
- University of Rochester Medical Center, Department of Cardiothoracic Surgery. 601 Elmwood Ave. Rochester, NY 1464
| | - Roger Zhu
- Montefiore Medical Center/ Albert Einstein College of Medicine. Department of Cardiothoracic and Vascular Surgery. 3400 Bainbridge. Bronx, New York. 10467
| | - Marc Vimolratana
- Montefiore Medical Center/ Albert Einstein College of Medicine. Department of Cardiothoracic and Vascular Surgery. 3400 Bainbridge. Bronx, New York. 10467
| | - Neel P Chudgar
- Montefiore Medical Center/ Albert Einstein College of Medicine. Department of Cardiothoracic and Vascular Surgery. 3400 Bainbridge. Bronx, New York. 10467
| | - Brendon M Stiles
- Montefiore Medical Center/ Albert Einstein College of Medicine. Department of Cardiothoracic and Vascular Surgery. 3400 Bainbridge. Bronx, New York. 10467
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9
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Zhang W, Shen Z, Jiang J, Zhu S, Zhang P, Chen S, Kang M. Comparative efficacy of prophylactic protocols in reducing perioperative nausea and vomiting during video-assisted thoracoscopic radical resection of lung cancer. Sci Rep 2024; 14:9818. [PMID: 38684769 PMCID: PMC11059372 DOI: 10.1038/s41598-024-59687-z] [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: 11/18/2023] [Accepted: 04/13/2024] [Indexed: 05/02/2024] Open
Abstract
Lung cancer, a global mortality leader, often necessitates Video-Assisted Thoracoscopic (VATS) surgery. However, post-operative nausea and vomiting (PONV) is common, highlighting a need for effective management and prevention strategies in this context. A retrospective case-control study at Fujian Medical University Union Hospital evaluated patients undergoing VATS radical resection of lung cancer between May and September 2022. Patients were categorized based on PONV prevention methods, and data encompassing demographics, surgical history, and postoperative adverse events s were analyzed to assess the association between prophylactic protocols and PONV incidence. The Netupitant and Palonosetron Hydrochloride (NEPA) group showed a significant reduction in PONV occurrences post-surgery compared to Ondansetron (ONDA) and Control groups, emphasizing NEPA's efficacy in alleviating PONV symptoms (P < 0.05). Furthermore, following VATS radical resection of lung cancer, NEPA markedly reduced the intensity of PONV symptoms in patients. Both univariate and multivariate logistic analyses corroborated that NEPA independently reduces PONV risk, with its protective effect also apparent in susceptible populations like females and non-smokers. NEPA utilization markedly reduced both the incidence and severity of PONV in patients undergoing VATS radical resection of lung cancer, serving as an independent protective factor in mitigating PONV risk post-surgery.
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Affiliation(s)
- Weiguang Zhang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Zhimin Shen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Junfei Jiang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Shujing Zhu
- The School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
| | - Peipei Zhang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Sui Chen
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China
| | - Mingqiang Kang
- Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
- Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China.
- Fujian Key Laboratory of Tumor Microbiology, Fujian Medical University, Fuzhou, China.
- Clinical Research Center for Thoracic Tumors of Fujian Province, Fuzhou, China.
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10
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Christ SM, Pohl K, Willmann J, Heesen P, Heusel A, Ahmadsei M, Kühnis A, Vlaskou Badra E, Muehlematter UJ, Mayinger M, Balermpas P, Andratschke N, Zaorsky N, Huellner M, Guckenberger M. Patterns of metastatic spread and tumor burden in unselected cancer patients using PET imaging: Implications for the oligometastatic spectrum theory. Clin Transl Radiat Oncol 2024; 45:100724. [PMID: 38288311 PMCID: PMC10823052 DOI: 10.1016/j.ctro.2024.100724] [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: 07/22/2023] [Revised: 12/08/2023] [Accepted: 01/07/2024] [Indexed: 01/31/2024] Open
Abstract
Introduction and background Metastatic disease has been proposed as a continuum, with no clear cut-off between oligometastatic and polymetastatic disease. This study aims to quantify tumor burden and patterns of spread in unselected metastatic cancer patients referred for PET-based staging, response assessment of restaging. Materials and methods All oncological fluorodeoxyglucose (FDG-) and prostate-specific membrane antigen (PSMA-) positron emission tomography (PET) scans conducted at a single academic center in 2020 were analyzed. Imaging reports of all patients with metastatic disease were reviewed and assessed. Results For this study, 7,000 PET scans were screened. One third of PET scans (n = 1,754; 33 %) from 1,155 unique patients showed presence of metastatic disease from solid malignancies, of which 601 (52 %) and 554 (48 %) were classified as oligometastatic (maximum 5 metastases) and polymetastatic (>5 metastases), respectively. Lung and pleural cancer, skin cancer, and breast cancer were the most common primary tumor histologies with 132 (23.8 %), 88 (15.9 %), and 72 (13.0 %) cases, respectively. Analysis of the number of distant metastases showed a strong bimodal distribution of the metastatic burden with 26 % of patients having one solitary metastasis and 43 % of patients harboring >10 metastases. Yet, despite 43 % of polymetastatic patients having >10 distant metastases, their pattern of distribution was restricted to one or two organs in about two thirds of patients, and there was no association between the number of distant metastases and the number of involved organs. Conclusion The majority of metastatic cancer patients are characterized by either a solitary metastasis or a high tumor burden with >10 metastases, the latter was often associated with affecting a limited number of organs. These findings support both the spectrum theory of metastasis and the seed and soil hypothesis and can support in designing the next generation of clinical trials in the field of oligometastatic disease.
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Affiliation(s)
- Sebastian M. Christ
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Kaspar Pohl
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Jonas Willmann
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
- Center for Proton Therapy, Paul Scherrer Institute, ETH Domain, Villigen, Switzerland
| | - Philip Heesen
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Astrid Heusel
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Maiwand Ahmadsei
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Anja Kühnis
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Eugenia Vlaskou Badra
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Urs J. Muehlematter
- Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Michael Mayinger
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Panagiotis Balermpas
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Nicolaus Andratschke
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Nicholas Zaorsky
- Department of Radiation Oncology, University Hospitals Seidman Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA
| | - Martin Huellner
- Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Matthias Guckenberger
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
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DEZZANI EO. Il fumo di sigarette e il tumore del polmone. GAZZETTA MEDICA ITALIANA ARCHIVIO PER LE SCIENZE MEDICHE 2024; 182. [DOI: 10.23736/s0393-3660.23.05425-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Meng Y, Sun H, Wang S, Yang H, Kong FMS. Treatment-Related Pneumonitis of EGFR Tyrosine Kinase Inhibitors Plus Thoracic Radiation Therapy in Patients With Non-Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. Int J Radiat Oncol Biol Phys 2024; 118:415-426. [PMID: 37716460 DOI: 10.1016/j.ijrobp.2023.09.009] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/08/2023] [Revised: 08/22/2023] [Accepted: 09/04/2023] [Indexed: 09/18/2023]
Abstract
Thoracic radiation therapy (RT) for non-small cell lung cancers may overcome resistance to tyrosine kinase inhibitors (TKIs). However, the risk of severe treatment-related pneumonitis (TRP) is a major concern, and the results of the combined treatment remain controversial. Therefore, we aimed to systematically review existing publications and provide a meta-analysis of TRP from a combined therapy of thoracic RT and TKIs. A systematic literature review was performed using the PubMed-MEDLINE and Embase databases to identify eligible publications. The number of severe TRP cases of grade 3 or higher was extracted and then analyzed by fixed or randomized model meta-analysis. Heterogeneity tests were performed using the I² and τ² statistics. Subgroup analyses were conducted on the types of RT and the sequence of the combined treatment. Our literature search identified 37 eligible studies with 1143 patients. Severe TRP occurred in 3.8% (95% CI, 1.8%-6.5%) of patients overall, and fatal pneumonitis occurred rarely in 0.1% (95% CI, 0.0%-0.3%). In the subgroup analysis, the severe TRP proportion was 2.3% (95% CI, 1.0%-4.1%) for patients under definitive (chemo)RT (19 studies, n = 702) versus 2.9% (95% CI, 1.3%-5.1%) for patients who received local stereotactic body RT or palliative RT (15 studies, n = 361). The severe TRP rate was 4.9% (95% CI, 2.4%-8.1%) for concurrent TKI and RT (26 studies, n = 765), which was significantly higher than TRP of 0.4% (95% CI, 0.0%-3.1%) for sequential therapy (6 studies, n = 200). Our meta-analysis showed that combined thoracic RT and epidermal growth factor receptor-TKI therapy has an acceptable risk of severe TRP and rare mortality in patients with non-small cell lung cancers. Concurrent treatment is less tolerable and should be administered with caution. Further investigations using osimertinib are required as the data on its effects are limited.
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Affiliation(s)
- Yinnan Meng
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Han Sun
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital & Shenzhen Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Shenzhen, China
| | - Sichao Wang
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Haihua Yang
- Department of Radiation Oncology, Affiliated Taizhou Hospital of Wenzhou Medical University, Taizhou, Zhejiang Province, China
| | - Feng-Ming Spring Kong
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China; Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.
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13
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Tong Y, Jiang L, Gong Y, Zhu D, Zhao D. Analysis of survival benefit from primary tumor resection and individualized prediction of overall survival for lung cancer patients with bone metastasis: Worth it or not? Asian J Surg 2024; 47:333-349. [PMID: 37741753 DOI: 10.1016/j.asjsur.2023.08.198] [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: 04/12/2023] [Revised: 08/15/2023] [Accepted: 08/30/2023] [Indexed: 09/25/2023] Open
Abstract
BACKGROUND The clinical management of lung cancer (LC) patients with bone metastasis (BM) is still a significant challenge. This study aimed to explore the role of primary tumor resection (PTR) on survival outcome of LC patients with BM and to develop two web-based nomograms for predicting the overall survival (OS) of LC patients with BM who received PTR and those who did not. METHODS We enrolled LC patients with BM from the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2015. Propensity score matching (PSM) was then conducted to balance the baseline characteristics of covariates between patients in surgery and non-surgery groups. Next, Kaplan-Meier analysis with log-rank test was performed to evaluate the survival benefit of PTR before and after PSM methods and to explore the impact of surgical resection extent on the prognosis of LC patients with BM and clinical outcomes in patients with different metastatic patterns. Cox proportional hazard regression analysis was then applied to determine the independent prognostic factors for OS of patients receiving PTR and did not receiving PTR, respectively. Subsequently, we constructed two individualized nomograms for predicting the 12-, 18- and 24-months OS. Finally, receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were generated to evaluate discrimination, accuracy and clinical utility of the nomograms. RESULTS A total of 7747 eligible patients were included in this analysis. The survival analysis revealed that PTR was closely associated with better survival outcome among LC patients with BM(P < 0.05), while the survival benefit of PTR was suboptimal in patients presented with multiple metastases(P > 0.05). Besides, lobectomy shows best survival benefit. Two nomograms were then constructed based on independent prognostic factors of patients in the surgery group and the non-surgery group. The ROC curves showed good discrimination of the two nomograms, with the area under curve (AUC) of each time point being higher than 0.7 in both the training set and testing set. The calibration curves also demonstrated satisfactory consistency between actual survival and nomogram-predicted OS of both nomograms. The DCA showed high benefit of nomogram in a clinical context. Moreover, the study population was stratified into three groups based on the scores of the nomogram, and the survival analysis showed that this prognostic stratification was statistically significant (p < 0.05). CONCLUSIONS This study showed that surgical resection of the primary site strategy can prolong survival of LC patients with BM to some extent, depending on different sites of metastasis and highly selected patients. Furthermore, the web-based nomograms showed significant accuracy in predicting OS for patients with or without surgery, which may provide valuable insights for patients' counseling and individualized decision-making for clinicians.
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Affiliation(s)
- Yuexin Tong
- Department of Orthopedics, The China-Japan Union Hospital of Jilin University, No 126 Xiantai Street, Changchun, Jilin, 130033, PR China
| | - Liming Jiang
- Department of Orthopedics, The China-Japan Union Hospital of Jilin University, No 126 Xiantai Street, Changchun, Jilin, 130033, PR China
| | - Yan Gong
- Department of Orthopedics, The China-Japan Union Hospital of Jilin University, No 126 Xiantai Street, Changchun, Jilin, 130033, PR China
| | - Dejing Zhu
- Department of Orthopedics, The China-Japan Union Hospital of Jilin University, No 126 Xiantai Street, Changchun, Jilin, 130033, PR China
| | - Dongxu Zhao
- Department of Orthopedics, The China-Japan Union Hospital of Jilin University, No 126 Xiantai Street, Changchun, Jilin, 130033, PR China.
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14
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Ampil F, Porter C, Sangster G, Toms J, Bozeman A. Correlation Between Oligometastatic Tumor in Two Other Visceral Organs and Prognosis in Patients With Brain Metastases. J Palliat Med 2023; 26:1715-1718. [PMID: 37917925 DOI: 10.1089/jpm.2022.0612] [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] [Indexed: 11/04/2023] Open
Abstract
Background and Objective: A recent report indicated that metastases to other body organs commonly develop after stereotactic body radiation treatment for cure in patients with oligometastases (OGM) confined to one organ. This study was undertaken to determine if the presence of metastatic disease in two other visceral organs (TVO) in patients with conventionally treated brain metastases (BRM) was associated with poorer prognosis. Methods: This retrospective clinical investigation included 26 patients treated for palliation of OGM-BRM between May 1996 and February 2020. These individuals were classified according to the presence (13 patients) or absence (13 patients) of metastases in TVO. Results: With an overall mean follow-up of 16 months, 20 patients were deceased, and 6 patients were alive. The median survivals for the OGM-BRM-TVO and non-OGM-BRM-TVO subsets were 4 and 12 months, respectively; the corresponding crude survival rates at 12 months were 0% and 46% (p < 0.01). Subgroup analysis correlating prognosis to the number of BRM (single vs. multiple) and OGM-BRM categories (synchronous vs. metachronous) failed to reveal a survival advantage favoring a certain subgroup. Conclusion: Although the evidence is speculative, we believe that an aggressive disease condition is more likely present in patients with OGM-BRM-TVO. With the notion of an overall poor survival, we suggest a more tailored, less or nonharmful management approach (i.e., palliative therapy or hospice) for this particular patient cohort.
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Affiliation(s)
- Federico Ampil
- Department of Radiology and Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA
| | - Carrie Porter
- Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA
| | - Guillermo Sangster
- Department of Radiology and Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA
| | - Jamie Toms
- Department of Neurosurgery, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA
| | - Amy Bozeman
- Feist-Weiller Cancer Center, Louisiana State University Health Sciences Center, Shreveport, Louisiana, USA
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15
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Lee J, Kim JA, An TJ, Lee H, Han EJ, Sa YJ, Kim HR, Park CK, Kim TJ, Lim JU. Optimal timing for local ablative treatment of bone oligometastases in non-small cell lung cancer. J Bone Oncol 2023; 42:100496. [PMID: 37589036 PMCID: PMC10425942 DOI: 10.1016/j.jbo.2023.100496] [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: 06/23/2023] [Revised: 07/29/2023] [Accepted: 07/31/2023] [Indexed: 08/18/2023] Open
Abstract
Oligometastases is a term commonly used to describe a disease state characterized by a limited number of distant metastases, and represents a transient phase between localized and widespread systemic diseases. This subgroup of stage IV cancer has increased in clinical importance due to the possibility of curative rather than palliative treatment. Among advanced lung cancer patients, 30-40% show bone metastases, and can show complications such as pathological fractures. Many prospective studies have shown efficacy of localized treatment in oligometastatic non-small cell lung cancer (NSCLC) in improving progression-free survival and overall survival. Compared to metastases in other organs, bone metastases are unique in terms of tumor microenvironment and clinical outcomes. Radiotherapy is the most frequently used treatment modality for local ablative treatment for both primary and metastatic lesions. Stereotactic body radiation therapy demonstrated more rapid and effective pain control compared to conventional 3D conformal radiotherapy. Radiotherapy improved outcomes in terms of time-to-skeletal related events skeletal-related events (SRE), hospitalization for SRE, pain relief, and overall survival in patients with bone metastases. Decision on timing of local ablative treatment depends on patient's overall clinical status, treatment goals, potential side effects of each approach, and expected initial responses to systemic anti-cancer treatment.
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Affiliation(s)
- Jayoung Lee
- Department of Radiation Oncology, The Catholic University of Korea, Yeouido St. Mary's Hospital, Seoul 150-713, Republic of Korea
| | - Jung A. Kim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 150-713, Republic of Korea
- Outpatient Department of Respiratory Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 150-713, Republic of Korea
| | - Tai Joon An
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 150-713, Republic of Korea
| | - Hyochun Lee
- Department of Radiation Oncology, The Catholic University of Korea, St. Vincent's Hospital, Republic of Korea
| | - Eun Ji Han
- Division of Nuclear Medicine, Department of Radiology, Yeouido St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 150-713, Republic of Korea
| | - Young Jo Sa
- Department of Thoracic and Cardiovascular Surgery, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 150-713, Republic of Korea
| | - Hyo Rim Kim
- Department of Radiology, College of Medicine, The Catholic University of Korea, Seoul 150-713, Republic of Korea
| | - Chan Kwon Park
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 150-713, Republic of Korea
| | - Tae-Jung Kim
- Department of Hospital Pathology, College of Medicine, The Catholic University of Korea, Seoul 150-713, Republic of Korea
| | - Jeong Uk Lim
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul 150-713, Republic of Korea
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Berghmans T, Brandão M. [Olimetastatic disease: Current status and perspectives in non-small cell lung cancer]. Rev Mal Respir 2023; 40:684-691. [PMID: 37500325 DOI: 10.1016/j.rmr.2023.07.002] [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: 03/10/2023] [Accepted: 06/22/2023] [Indexed: 07/29/2023]
Abstract
The concept of oligometastatic disease was first introduced in the late 1990s to describe an situation more or less midway between locally advanced tumours and multifocal metastatic cancer. Four concepts are currently used: synchronous oligometastatic disease, metachronous oligometastatic disease (or oligo-recurrence), oligo-persistence and oligo-progression. Some phase II studies, randomised or not, have validated this concept in non-small cell lung cancer (NSCLC) and suggest the interest of adding local ablative therapy to systemic treatment. That said, numerous questions remain, and the impact of this therapeutic approach in the framework of immunotherapies and targeted therapies has yet to be assessed. Which of these new treatments offer hope of significantly improved long-term survival in stage IV NSCLC? This article appraises current knowledge and therapeutic regarding oligometastatic NSCLC.
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Affiliation(s)
- T Berghmans
- Service d'oncologie médicale, clinique d'oncologie thoracique, Institut Jules-Bordet, hôpitaux universitaires de Bruxelles, Université Libre de Bruxelles, rue Meylemeersch, 90, 1170 Bruxelles, Belgique.
| | - M Brandão
- Service d'oncologie médicale, clinique d'oncologie thoracique, Institut Jules-Bordet, hôpitaux universitaires de Bruxelles, Université Libre de Bruxelles, rue Meylemeersch, 90, 1170 Bruxelles, Belgique
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Iyengar P, All S, Berry MF, Boike TP, Bradfield L, Dingemans AMC, Feldman J, Gomez DR, Hesketh PJ, Jabbour SK, Jeter M, Josipovic M, Lievens Y, McDonald F, Perez BA, Ricardi U, Ruffini E, De Ruysscher D, Saeed H, Schneider BJ, Senan S, Widder J, Guckenberger M. Treatment of Oligometastatic Non-Small Cell Lung Cancer: An ASTRO/ESTRO Clinical Practice Guideline. Pract Radiat Oncol 2023; 13:393-412. [PMID: 37294262 DOI: 10.1016/j.prro.2023.04.004] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2023] [Accepted: 04/07/2023] [Indexed: 06/10/2023]
Abstract
PURPOSE This joint guideline by American Society for Radiation Oncology (ASTRO) and the European Society for Radiotherapy and Oncology (ESTRO) was initiated to review evidence and provide recommendations regarding the use of local therapy in the management of extracranial oligometastatic non-small cell lung cancer (NSCLC). Local therapy is defined as the comprehensive treatment of all known cancer-primary tumor, regional nodal metastases, and metastases-with definitive intent. METHODS ASTRO and ESTRO convened a task force to address 5 key questions focused on the use of local (radiation, surgery, other ablative methods) and systemic therapy in the management of oligometastatic NSCLC. The questions address clinical scenarios for using local therapy, sequencing and timing when integrating local with systemic therapies, radiation techniques critical for oligometastatic disease targeting and treatment delivery, and the role of local therapy for oligoprogression or recurrent disease. Recommendations were based on a systematic literature review and created using ASTRO guidelines methodology. RESULTS Based on the lack of significant randomized phase 3 trials, a patient-centered, multidisciplinary approach was strongly recommended for all decision-making regarding potential treatment. Integration of definitive local therapy was only relevant if technically feasible and clinically safe to all disease sites, defined as 5 or fewer distinct sites. Conditional recommendations were given for definitive local therapies in synchronous, metachronous, oligopersistent, and oligoprogressive conditions for extracranial disease. Radiation and surgery were the only primary definitive local therapy modalities recommended for use in the management of patients with oligometastatic disease, with indications provided for choosing one over the other. Sequencing recommendations were provided for systemic and local therapy integration. Finally, multiple recommendations were provided for the optimal technical use of hypofractionated radiation or stereotactic body radiation therapy as definitive local therapy, including dose and fractionation. CONCLUSIONS Presently, data regarding clinical benefits of local therapy on overall and other survival outcomes is still sparse for oligometastatic NSCLC. However, with rapidly evolving data being generated supporting local therapy in oligometastatic NSCLC, this guideline attempted to frame recommendations as a function of the quality of data available to make decisions in a multidisciplinary approach incorporating patient goals and tolerances.
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Affiliation(s)
- Puneeth Iyengar
- Department of Radiation Oncology, UT Southwestern, Dallas, Texas.
| | - Sean All
- Department of Radiation Oncology, UT Southwestern, Dallas, Texas
| | - Mark F Berry
- Department of Cardiothoracic Surgery, Stanford University, Palo Alto, California
| | - Thomas P Boike
- Department of Radiation Oncology, GenesisCare/MHP Radiation Oncology, Troy, Michigan
| | - Lisa Bradfield
- American Society for Radiation Oncology, Arlington, Virginia
| | - Anne-Marie C Dingemans
- Department of Pulmonology, Erasmus Medical Center Cancer Institute, University Medical Center, Rotterdam, The Netherlands
| | | | - Daniel R Gomez
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, New York
| | - Paul J Hesketh
- Department of Internal Medicine, Lahey Hospital and Medical Center, Burlington, Massachusetts
| | - Salma K Jabbour
- Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey
| | - Melenda Jeter
- Department of Radiation Oncology, MD Anderson Cancer Center, Houston, Texas
| | | | - Yolande Lievens
- Department of Radiation Oncology, Ghent University Hospital and Ghent University, Ghent, Belgium
| | - Fiona McDonald
- Department of Radiation Oncology, Royal Marsden Hospital, London, United Kingdom
| | - Bradford A Perez
- Department of Radiation Oncology, Moffitt Cancer Center, Tampa, Florida
| | | | - Enrico Ruffini
- Department of Thoracic Surgery, University of Torino, Torino, Italy
| | - Dirk De Ruysscher
- Department of Radiation Oncology (MAASTRO), Maastricht University Medical Centre, Maastricht and Erasmus Medical Center, University Medical Center, Rotterdam, The Netherlands
| | - Hina Saeed
- Department of Radiation Oncology, Baptist Health South Florida, Boca Raton, Florida
| | - Bryan J Schneider
- Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
| | - Suresh Senan
- Department of Radiation Oncology, Amsterdam University Medical Centers, Cancer Center Amsterdam, Amsterdam, The Netherlands
| | - Joachim Widder
- Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Matthias Guckenberger
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
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18
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AÇIKGÖZ Ö, BİLİCİ A, TATAROĞLU ÖZYÜKSELER D, GÖKTAŞ AYDIN S, SELÇUKBİRİCİK F, RZAZADE R, ÖLMEZ ÖF, BAŞAK ÇAĞLAR H. Survival outcomes of patients with oligometastatic non-small cell lung cancer who were treated with radical therapy: a multicenter analysis. Turk J Med Sci 2023; 53:949-961. [PMID: 38031948 PMCID: PMC10760583 DOI: 10.55730/1300-0144.5659] [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: 08/29/2022] [Revised: 08/18/2023] [Accepted: 02/01/2023] [Indexed: 12/01/2023] Open
Abstract
BACKGROUND Oligometastatic disease for nonsmall cell lung cancer (NSCLC) patients is generally thought to represent a better prognosis with a quieter biology, limited number of disease sites and long-term disease control. In this study, we aimed to determine the efficacy of radical treatment options for patients with oligometastatic NSCLC. METHODS This retrospective trial included totally 134 patients with oligometastatic NSCLC. The presence of oncodriver mutation, tumor stages and nodal status, the number of metastases and involved metastatic site, treatment of primary tumor and oligometastasis, response rate, overall survival (OS) and progression-free survival (PFS) were evaluated. RESULTS Of 134 patients 66.4% were defined as adenocarcinoma, 26.1% were squamous cell carcinoma and 7.5% of patients were in other histology. Based on the treatment of primary tumor, in 36 patients (26.9%) curative surgery has undergone, in addition, 19 (14.2%) patients were received chemotherapy, 73 (54.5%) were treated with chemoradiotherapy, while immunotherapy and targeted therapy were used in 1 (0.7%) and 2 (1.4%), respectively. The preferred treatment for oligometastatic lesions were SBRT in 72.4% of patients, surgery in 10.5%, and both SBRT and surgery in 17.1% of patients. At the median follow up of 31.3 months (range: 9.5-48.5), the median PFS and OS times were 17 and 24.4 months, respectively. Moreover, OS-2 after progression was also 7.2 months. DISCUSSION Based on our real-life experience, we demonstrated a significant correlation between good response to first treatment and survival in oligometastatic disease, we also understand that local ablative treatment modalities prolong and also delay both OS and PFS in oligometastatic NSCLC patients OS-2.
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Affiliation(s)
- Özgür AÇIKGÖZ
- Department of Medical Oncology, Faculty of Medicine, İstanbul Medipol University, İstanbul,
Turkiye
| | - Ahmet BİLİCİ
- Department of Medical Oncology, Faculty of Medicine, İstanbul Medipol University, İstanbul,
Turkiye
| | - Deniz TATAROĞLU ÖZYÜKSELER
- Department of Medical Oncology, Dr. Lütfi Kırdar Kartal Education and Research Hospital, İstanbul,
Turkiye
| | - Sabin GÖKTAŞ AYDIN
- Department of Medical Oncology, Faculty of Medicine, İstanbul Medipol University, İstanbul,
Turkiye
| | - Fatih SELÇUKBİRİCİK
- Department of Medical Oncology, Faculty of Medicine, Koç University, İstanbul,
Turkiye
| | - Rashad RZAZADE
- Department of Radiation Oncology, Anadolu Health Center, Kocaeli,
Turkiye
| | - Ömer Fatih ÖLMEZ
- Department of Medical Oncology, Faculty of Medicine, İstanbul Medipol University, İstanbul,
Turkiye
| | - Hale BAŞAK ÇAĞLAR
- Department of Radiation Oncology, Anadolu Health Center, Kocaeli,
Turkiye
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Hendriks LE, Kerr KM, Menis J, Mok TS, Nestle U, Passaro A, Peters S, Planchard D, Smit EF, Solomon BJ, Veronesi G, Reck M. Non-oncogene-addicted metastatic non-small-cell lung cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up. Ann Oncol 2023; 34:358-376. [PMID: 36669645 DOI: 10.1016/j.annonc.2022.12.013] [Citation(s) in RCA: 256] [Impact Index Per Article: 128.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/09/2022] [Revised: 12/19/2022] [Accepted: 12/20/2022] [Indexed: 01/18/2023] Open
Affiliation(s)
- L E Hendriks
- Department of Pulmonology, GROW School for Oncology and Reproduction, Maastricht University Medical Center, Maastricht, The Netherlands
| | - K M Kerr
- Aberdeen Royal Infirmary, Aberdeen University Medical School, Aberdeen, UK
| | - J Menis
- Medical Oncology Department, University and Hospital Trust of Verona, Verona, Italy
| | - T S Mok
- Department of Clinical Oncology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, China
| | - U Nestle
- Department of Radiation Oncology, University Hospital Freiburg, Freiburg; Department of Radiation Oncology, Kliniken Maria Hilf, Moenchengladbach, Germany
| | - A Passaro
- Division of Thoracic Oncology, European Institute of Oncology IRCCS, Milan, Italy
| | - S Peters
- Department of Oncology, Centre Hospitalier Universitaire Vaudois, Lausanne University, Lausanne, Switzerland
| | - D Planchard
- Department of Medical Oncology, Thoracic Group, Gustave-Roussy, Villejuif, France
| | - E F Smit
- Thoracic Oncology Service, Netherlands Cancer Institute, Amsterdam; Department of Pulmonary Diseases, Leiden University Medical Center, Leiden, The Netherlands
| | - B J Solomon
- Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Australia
| | - G Veronesi
- Faculty of Medicine and Surgery-Vita-Salute San Raffaele University, Milan; Division of Thoracic Surgery, IRCCS San Raffaele Scientific Institute, Milan, Italy
| | - M Reck
- Department of Thoracic Oncology, Airway Research Center North, German Center for Lung Research, Lung Clinic, Grosshansdorf, Germany
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20
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Systematic Review of Tumor Segmentation Strategies for Bone Metastases. Cancers (Basel) 2023; 15:cancers15061750. [PMID: 36980636 PMCID: PMC10046265 DOI: 10.3390/cancers15061750] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 03/09/2023] [Accepted: 03/10/2023] [Indexed: 03/18/2023] Open
Abstract
Purpose: To investigate the segmentation approaches for bone metastases in differentiating benign from malignant bone lesions and characterizing malignant bone lesions. Method: The literature search was conducted in Scopus, PubMed, IEEE and MedLine, and Web of Science electronic databases following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A total of 77 original articles, 24 review articles, and 1 comparison paper published between January 2010 and March 2022 were included in the review. Results: The results showed that most studies used neural network-based approaches (58.44%) and CT-based imaging (50.65%) out of 77 original articles. However, the review highlights the lack of a gold standard for tumor boundaries and the need for manual correction of the segmentation output, which largely explains the absence of clinical translation studies. Moreover, only 19 studies (24.67%) specifically mentioned the feasibility of their proposed methods for use in clinical practice. Conclusion: Development of tumor segmentation techniques that combine anatomical information and metabolic activities is encouraging despite not having an optimal tumor segmentation method for all applications or can compensate for all the difficulties built into data limitations.
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21
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Huang JW, Lin YH, Chang GC, Chen JJW. A novel tool to evaluate and quantify radiation pneumonitis: A retrospective analysis of correlation of dosimetric parameters with volume of pneumonia patch. Front Oncol 2023; 13:1130406. [PMID: 36994217 PMCID: PMC10040686 DOI: 10.3389/fonc.2023.1130406] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2022] [Accepted: 02/21/2023] [Indexed: 03/18/2023] Open
Abstract
IntroductionIn lung cancer, radiation-induced lung injury (RILI) or radiation pneumonitis (RP) are major concerns after radiotherapy. We investigated the correlation between volumes of RP lesions and their RP grades after radiotherapy.Methods and materialsWe retrospectively collected data from patients with non-small lung cancer that received curative doses to the thorax without undergoing chest radiotherapy before this treatment course. The post-treatment computed tomography (CT) image was used to register to the planning CT to evaluate the correlation between dosimetric parameters and volume of pneumonia patch by using deformable image registration.ResultsFrom January 1, 2019, to December 30, 2020, 71 patients with non-small cell lung cancer with 169 sets of CT images met our criteria for evaluation. In all patient groups, we found the RPv max and RP grade max to be significant (p<0.001). Some parameters that were related to the dose-volume histogram (DVH) and RP were lung Vx (x=1-66 Gy, percentage of lung volume received ≥x Gy), and mean lung dose. Comparing these parameters of the DVH with RP grade max showed that the mean lung dose and lung V1–V31 were significantly correlated. The cut-off point for the occurrence of symptoms in all patient groups, the RPv max value, was 4.79%, while the area under the curve was 0.779. In the groups with grades 1 and 2 RP, the dose curve of 26 Gy covered ≥80% of RP lesions in >80% of patients. Patients who had radiotherapy in combination with chemotherapy had significantly shorter locoregional progression-free survival (p=0.049) than patients who received radiation therapy in combination with target therapy. Patients with RPv max >4.79% demonstrated better OS (p=0.082).ConclusionThe percentage of RP lesion volume to total lung volume is a good indicator for quantifying RP. RP lesions can be projected onto the original radiation therapy plan using coverage of the 26 Gy isodose line to determine whether the lesion is RILI.
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Affiliation(s)
- Jing-Wen Huang
- Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan
- Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
| | - Yi-Hui Lin
- Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Gee-Chen Chang
- Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
- Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
- Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan
- School of Medicine, Chung Shan Medical University, Taichung, Taiwan
- *Correspondence: Gee-Chen Chang, ; Jeremy J. W. Chen,
| | - Jeremy J. W. Chen
- Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
- *Correspondence: Gee-Chen Chang, ; Jeremy J. W. Chen,
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22
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Metzenmacher M, Griesinger F, Hummel HD, Elender C, Schäfer H, de Wit M, Kaiser U, Kern J, Jänicke M, Spring L, Zacharias S, Kaiser-Osterhues A, Groth A, Hipper A, Zaun G, Dörfel S, Güldenzoph B, Müller L, Uhlig J, Thomas M, Sebastian M, Eberhardt WE. Prognostic factors in nonsmall cell lung cancer: insights from the German CRISP registry. Eur Respir J 2023; 61:13993003.01336-2022. [PMID: 36180086 PMCID: PMC9892864 DOI: 10.1183/13993003.01336-2022] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Accepted: 09/04/2022] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Understanding prognosis, especially long-term outcome, in advanced nonsmall cell lung cancer (NSCLC) is crucial to inform patients, guide treatment and plan supportive and palliative care. METHODS Prognostic factors influencing overall survival (OS) and progression-free survival (PFS) in 2082 patients with wild-type (WT)-NSCLC (629 M1a, 249 M1b, 1204 M1c) are reported. Patients were included in the prospective German CRISP registry recruiting in >150 centres. Analysis for pre-therapeutic factors was based on results from Cox proportional hazard models. RESULTS Current M-descriptors of the Union for International Cancer Control-8 staging system were validated: M1a and M1b patients had significantly longer median time to events compared to M1c (OS/PFS 16.4/7.2 months, 17.8/6.7 months and 10.9/5.4 months, respectively). OS and PFS were influenced by number and location of metastatic organ systems. M1c and four or more metastatic organs involved had shorter OS and PFS than M1c with one to three organs (OS hazard ratio (HR) 1.69, p<0.001; PFS HR 1.81, p<0.001). M1b-liver metastases had shorter OS/PFS than M1b involving other organs (OS HR 2.70, p=0.006; PFS HR 2.48, p=0.007). Based on number of involved organs (orgsys) and liver metastases, two risk groups (low-risk: M1a, M1b-non-liver, M1c-1-3-orgsys-non-liver; high-risk: M1c-liver, M1b-liver, M1c-4+-orgsys) with significantly different prognoses could be amalgamated (median OS/PFS 14.3/6.5 months and 7.7/4.1 months, respectively). Other favourable factors were female gender and Eastern Cooperative Oncology Group stage 0, with age showing no impact. Those with T1- or N0-status were associated with longer OS than T2-4 or N2-3. CONCLUSION In this large observational dataset, we further defined factors for outcome in WT-NSCLC, including increased number of involved metastatic organ systems and liver metastases, as those with overall poorer prognosis and reduced survival chance.
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Affiliation(s)
- Martin Metzenmacher
- Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany
- Division of Thoracic Oncology, West German Cancer Center, University Medicine Essen – Ruhrlandklinik, Essen, Germany
| | - Frank Griesinger
- Department of Haematology and Oncology, University Dept Internal Medicine-Oncology, Pius-Hospital, University Medicine Oldenburg, Oldenburg, Germany
| | - Horst-Dieter Hummel
- Interdisziplinäres Studienzentrum mit ECTU/Translationale Onkologie, Comprehensive Cancer Center, Mainfranken, Universitätsklinikum Würzburg, Würzburg, Germany
| | - Corinna Elender
- Pneumologie, Infektiologie, Internistische Intensivmedizin, Klinik Nord im Klinikum Dortmund, Dortmund, Germany
| | - Harald Schäfer
- Pneumologie, Thorakale Onkologie, Palliativmedizin, Infektiologie, SHG Kliniken Völklingen, Völklingen, Germany
| | - Maike de Wit
- Klinik für Innere Medizin – Hämatologie, Onkologie und Palliativmedizin, Vivantes Klinikum Neukölln, Berlin, Germany
| | - Ulrich Kaiser
- Medizinische Klinik II, Hämatologie & Internistische Onkologie, St. Bernward Krankenhaus, Hildesheim, Germany
| | - Jens Kern
- Klinikum Würzburg Mitte – Standort Missioklinik, Med. Klinik mit Schwerpunkt Pneumologie, Würzburg, Germany
| | - Martina Jänicke
- Clinical Epidemiology and Health Economics, iOMEDICO, Freiburg, Germany
| | - Lisa Spring
- Clinical Epidemiology and Health Economics, iOMEDICO, Freiburg, Germany
| | | | | | | | | | - Gregor Zaun
- Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany
| | | | - Björn Güldenzoph
- Hämatologisch-Onkologische Praxis Altona (HOPA), Hamburg, Germany
| | | | - Jens Uhlig
- Praxis Dr. med. Jens Uhlig, Naunhof, Germany
| | - Michael Thomas
- Department of Thoracic Oncology, Thoraxklinik, University Hospital Heidelberg and Translational, Lung Research Center Heidelberg (TLRC-H), Member of the German Center for Lung Research (DZL), Heidelberg, Germany
| | - Martin Sebastian
- Department of Hematology and Medical Oncology, University Hospital Frankfurt, Frankfurt, Germany
| | - Wilfried E.E. Eberhardt
- Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany
- Division of Thoracic Oncology, West German Cancer Center, University Medicine Essen – Ruhrlandklinik, Essen, Germany
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23
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Khadela A, Chavda VP, Postwala H, Ephraim R, Apostolopoulos V, Shah Y. Configuring Therapeutic Aspects of Immune Checkpoints in Lung Cancer. Cancers (Basel) 2023; 15:543. [PMID: 36672492 PMCID: PMC9856297 DOI: 10.3390/cancers15020543] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/25/2022] [Accepted: 01/13/2023] [Indexed: 01/18/2023] Open
Abstract
Immune checkpoints are unique components of the body's defense mechanism that safeguard the body from immune responses that are potent enough to harm healthy body cells. When proteins present on the surface of T cells recognize and bind to the proteins present on other tumor cells, immune checkpoints are triggered. These proteins are called immunological checkpoints. The T cells receive an on/off signal when the checkpoints interact with companion proteins. This might avert the host's immune system from eliminating cancer cells. The standard care plan for the treatment of non-small cell lung cancer (NSCLC) has been revolutionized with the use of drugs targeting immune checkpoints, in particular programmed cell death protein 1. These drugs are now extended for their potential to manage SCLC. However, it is acknowledged that these drugs have specific immune related adverse effects. Herein, we discuss the use of immune checkpoint inhibitors in patients with NSCLC and SCLC, their outcomes, and future perspectives.
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Affiliation(s)
- Avinash Khadela
- Department of Pharmacology, L. M. College of Pharmacy, Navrangpura, Ahmedabad 380009, Gujarat, India
| | - Vivek P. Chavda
- Department of Pharmaceutics and Pharmaceutical Technology, L. M. College of Pharmacy, Navrangpura, Ahmedabad 380009, Gujarat, India
| | - Humzah Postwala
- Pharm. D Section, L. M. College of Pharmacy, Navrangpura, Ahmedabad 380009, Gujarat, India
| | - Ramya Ephraim
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia
| | - Vasso Apostolopoulos
- Institute for Health and Sport, Victoria University, Melbourne, VIC 3030, Australia
- Australian Institute for Musculoskeletal Science, Melbourne, VIC 3021, Australia
| | - Yesha Shah
- Pharm. D Section, L. M. College of Pharmacy, Navrangpura, Ahmedabad 380009, Gujarat, India
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Christ SM, Heesen P, Muehlematter UJ, Pohl K, William Thiel G, Willmann J, Ahmadsei M, Kroese TE, Mayinger M, Balermpas P, Wicki A, Andratschke N, Huellner M, Guckenberger M. Recognition of and treatment recommendations for oligometastatic disease in multidisciplinary tumor boards. Clin Transl Radiat Oncol 2023; 38:123-129. [PMID: 36420098 PMCID: PMC9676209 DOI: 10.1016/j.ctro.2022.11.008] [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: 10/03/2022] [Revised: 11/08/2022] [Accepted: 11/10/2022] [Indexed: 11/17/2022] Open
Abstract
Background and introduction Growing evidence supports a combined modality treatment strategy for patients with oligometastatic disease. However, lack of phase III trial data and uncertainties around patient selection highlight the importance of multidisciplinary tumor boards (MDT) in therapeutic decision-making. This study aimed to analyze the recognition of and treatment recommendations for oligometastatic patients by MDTs at a large comprehensive cancer center in order to better understand current treatment patterns of oligometastasis. Materials and methods For this retrospective single-center cross-sectional study, oligometastatic patients were identified by screening oncological PET and concurrent brain MRI scans conducted at our center in 2020. MDT discussions and recommendations within four weeks of the imaging diagnosis of oligometastasis were analyzed. Logistic regression analysis was used to identify predictors for the addition of local therapy to standard-of-care. Results A total of 787 oligometastatic cases were identified. Lung cancer and mesothelioma, skin cancer, and prostate cancer were the most common histologies with 231 (29 %), 160 (20 %), and 84 (11 %) cases, respectively. Almost half of the cases (46 %) had one distant metastasis on imaging only. More than half (56 %) of all oligometastatic cases were discussed at an MDT. In 47 % of cases, for which a therapeutic recommendation was reached in an MDT, local therapy was part of the therapeutic strategy. On logistic regression analysis, oligometastatic skin cancer was significantly associated with a recommendation for local therapy (p < 0.05), whereas the number of oligometastases was not (p = 0.202). Conclusion More than half of oligometastatic cases were discussed in MDTs, of which more than every second received a recommendation including the addition of local therapy. This frequency of MDT use underscores the importance of multidisciplinary decision-making, yet efforts should be increased to standardize reporting and use standard nomenclature on oligometastasis in MDTs to better frame multidisciplinary discussion.
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Affiliation(s)
- Sebastian M. Christ
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Philip Heesen
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | - Urs J. Muehlematter
- Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Kaspar Pohl
- Faculty of Medicine, University of Zurich, Zurich, Switzerland
| | | | - Jonas Willmann
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Maiwand Ahmadsei
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Tiuri E. Kroese
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Michael Mayinger
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Panagiotis Balermpas
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Andreas Wicki
- Department of Medical Oncology and Hematology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Nicolaus Andratschke
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Martin Huellner
- Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Matthias Guckenberger
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
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Zhang J, Mao J, Xu D, Jiang S, Guo T, Zhou Y, Chu L, Yang X, Chu X, Ni J, Zhu Z. Pattern of failure and clinical value of local therapy for oligo‐recurrence in locally advanced non‐small cell lung cancer after definitive chemoradiation: Impact of driver mutation status. Cancer Med 2022; 12:6971-6979. [PMID: 36524618 PMCID: PMC10067091 DOI: 10.1002/cam4.5493] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2022] [Revised: 11/14/2022] [Accepted: 11/19/2022] [Indexed: 12/23/2022] Open
Abstract
INTRODUCTION Considerable differences of treatment response and pattern of failure may exist between definitive chemoradiation (CRT) treated locally advanced non-small cell lung cancer (LA-NSCLC) patients. The clinical value of additional tyrosine kinase inhibitors (TKIs) before disease recurrence and salvage local therapy after initial recurrent disease remain controversial. METHODS AND MATERIALS Consecutive LA-NSCLC patients receiving definitive CRT and having definite results about driver mutations (EGFR, ALK and ROS1) were retrospectively reviewed. Initial recurrent disease was classified as in-field recurrence, out-of-field recurrence and distant metastasis. Recurrent disease occurred only in the brain or limited to ≤3 extra-cranial organs and ≤5 extra-cranial lesions, was defined as oligo-recurrence. Progression free survival and overall survival (OS) were calculated from diagnosis to disease progression or death, and to death, respectively. OS2 was measured from initial disease recurrence to death among patients who had recurrent disease. RESULTS Of the 153 enrolled patients, 39 had driver mutations and 13 received additional TKI therapy besides definitive CRT. Patients harboring driver mutations but without additional TKI therapy had a similar PFS and significantly longer OS (p = 0.032) than those without driver mutations. Additional TKI therapy prolonged PFS (p = 0.021) but not OS among patients with driver mutations. No significant difference of pattern of failure was observed between patient subgroups stratified by the status of driver mutations and the usage of additional TKI therapy. Furthermore, 57 of the 95 patients with initial recurrent disease developed oligo-recurrence and salvage local therapy significantly improved OS2 (p = 0.01) among patients with oligo-recurrence disease. CONCLUSION LA-NSCLC patients receiving definitive CRT generally had similar PFS and pattern of treatment failure, regardless of driver mutation status. Additional TKI therapy besides definitive CRT could prolong PFS but not OS. The majority of recurrent disease after definitive CRT belongs to oligo-recurrence and salvage local therapy may provide survival benefit.
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Affiliation(s)
- Jinmeng Zhang
- Department of Radiation Oncology Fudan University Shanghai Cancer Center Shanghai China
- Department of Oncology, Shanghai Medical College Fudan University Shanghai China
| | - Jiuang Mao
- Department of Radiation Oncology Fudan University Shanghai Cancer Center Shanghai China
- Department of Oncology, Shanghai Medical College Fudan University Shanghai China
| | - Dayu Xu
- Department of Radiation Oncology Fudan University Shanghai Cancer Center Shanghai China
- Department of Oncology, Shanghai Medical College Fudan University Shanghai China
| | - Shanshan Jiang
- 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
| | - Yue Zhou
- 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
| | - Xi Yang
- 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
| | - Jianjiao Ni
- 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
- Shanghai Clinical Research Center for Radiation Oncology Shanghai China
- Shanghai Key Laboratory of Radiation Oncology Shanghai China
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Zhang S, Sun Q, Cai F, Li H, Zhou Y. Local therapy treatment conditions for oligometastatic non-small cell lung cancer. Front Oncol 2022; 12:1028132. [PMID: 36568167 PMCID: PMC9773544 DOI: 10.3389/fonc.2022.1028132] [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: 08/25/2022] [Accepted: 11/23/2022] [Indexed: 12/13/2022] Open
Abstract
Standard treatments for patients with metastatic non-small cell lung cancer (NSCLC) include palliative chemotherapy and radiotherapy, but with limited survival rates. With the development of improved immunotherapy and targeted therapy, NSCLC prognoses have significantly improved. In recent years, the concept of oligometastatic disease has been developed, with randomized trial data showing survival benefits from local ablation therapy (LAT) in patients with oligometastatic NSCLC (OM-NSCLC). LAT includes surgery, stereotactic ablation body radiation therapy, or thermal ablation, and is becoming an important treatment component for OM-NSCLC. However, controversy remains on specific management strategies for the condition. In this review, we gathered current randomized trial data to analyze prognostic factors affecting patient survival, and explored ideal treatment conditions for patients with OM-NSCLC with respect to long-term survival.
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Affiliation(s)
- Suli Zhang
- Department of Radiation Oncology, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui, China
| | - Qian Sun
- Department of Radiation Oncology, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui, China,*Correspondence: Yufu Zhou, ; Qian Sun,
| | - Feng Cai
- Department of Radiation Oncology, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui, China
| | - Hui Li
- Department of Nuclear Medicine, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui, China
| | - Yufu Zhou
- Department of Radiation Oncology, First Affiliated Hospital, Bengbu Medical College, Bengbu, Anhui, China,*Correspondence: Yufu Zhou, ; Qian Sun,
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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.
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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.)
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Oligometastatic Non-Small Cell Lung Cancer: A Practical Review of Prospective Trials. Cancers (Basel) 2022; 14:cancers14215339. [PMID: 36358757 PMCID: PMC9658224 DOI: 10.3390/cancers14215339] [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: 09/01/2022] [Revised: 10/18/2022] [Accepted: 10/28/2022] [Indexed: 12/03/2022] Open
Abstract
Simple Summary A significant number of patients diagnosed with non-small cell lung cancer (NSCLC) will have a metastatic Stage IV disease at presentation. Among those, patients with limited number of metastases are referred to as oligometastatic, and their treatment will combine systemic and possible local therapy. The aim of this article is to review the current definition of oligometastatic cancer, a historic perspective of lung cancer leading to modern oligometastatic disease and to present available prospective evidence for treatment of oligometastatic NSCLC. We describe trials exploring role of local therapy in oligometastatic NSCLC with actionable mutation in combination with TKI or without any actionable mutation and in combination with chemo-immunotherapy. We also discuss general treatment approaches adopted based on limited data. Finally, we discuss the on-going clinical trials for oligometastatic and oligoprogressive NSCLC. Abstract Oligometastatic non-small cell lung cancer (NSCLC) is an intermediate state between localized and widely metastatic NSCLC, where systemic therapy in combination with aggressive local therapy when feasible can yield a favorable outcome. While different societies have adopted different definitions for oligometastatic NSCLC, the feasibility of curative intent treatment remains a major determinant of the oligometastatic state. The management involves a multidisciplinary approach to identify such patients with oligometastatic stage, including the presence of symptomatic or potentially symptomatic brain metastasis, the presence of targetable mutations, and programmed death-ligand (PD-L1) expression. Treatment requires a personalized approach with the use of novel systemic agents such as tyrosine kinase inhibitors and immune checkpoint inhibitors with or without chemotherapy, and addition of local ablative therapy via surgery or stereotactic radiation therapy when appropriate.
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Santos PMG, Li X, Gomez DR. Local Consolidative Therapy for Oligometastatic Non-Small Cell Lung Cancer. Cancers (Basel) 2022; 14:3977. [PMID: 36010969 PMCID: PMC9406686 DOI: 10.3390/cancers14163977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2022] [Revised: 07/21/2022] [Accepted: 07/22/2022] [Indexed: 11/30/2022] Open
Abstract
In the last 20 years, significant strides have been made in our understanding of the biological mechanisms driving disease pathogenesis in metastatic non-small cell lung cancer (NSCLC). Notably, the development and application of predictive biomarkers as well as refined treatment regimens in the form of chemoimmunotherapy and novel targeted agents have led to substantial improvements in survival. Parallel to these remarkable advancements in modern systemic therapy has been a growing recognition of "oligometastatic disease" as a distinct clinical entity-defined by the presence of a controlled primary tumor and ≤5 sites of metastatic disease amenable to local consolidative therapy (LAT), with surgery or stereotactic ablative body radiotherapy (SABR). To date, three randomized studies have provided clinical evidence supporting the use of LAT/SABR in the treatment of oligometastatic NSCLC. In this review, we summarize clinical evidence from these landmark studies and highlight ongoing trials evaluating the use of LAT/SABR in a variety of clinical contexts along the oligometastatic disease spectrum. We discuss important implications and caveats of the available data, including considerations surrounding patient selection and application in routine clinical practice. We conclude by offering potential avenues for further investigation in the oligometastatic disease space.
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Affiliation(s)
| | | | - Daniel R. Gomez
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
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Itchins M, Pavlakis N. The quantum leap in therapeutics for advanced ALK+ non-small cell lung cancer and pursuit to cure with precision medicine. Front Oncol 2022; 12:959637. [PMID: 36003760 PMCID: PMC9393505 DOI: 10.3389/fonc.2022.959637] [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: 06/01/2022] [Accepted: 07/08/2022] [Indexed: 11/13/2022] Open
Abstract
Since the discovery 15 years ago, we have seen a quantum leap in the treatment and survival for individuals diagnosed with ALK+ lung cancers. Unfortunately however, for most, the diagnosis is made in an incurable circumstance given the late presentation of symptoms. Through a revolutionary wave of therapeutics, individuals may remarkably live over a decade, however many fall short of this milestone, as the molecular profile of this disease is very heterogeneous, reflected in variable survival outcomes. Despite a significant improval in survival and quality of life with ALK-inhibitor monotherapies, now available across multiple-generations, drug resistance and disease relapse remains inevitable, and treatment is offered in an empiric, stepwise, non personalised biomarker informed fashion. A proposed future focus to treating ALK to improve the chronicity of this disease and even promote cure, is to deliver a personalised dynamic approach to care, with rational combinations of drugs in conjunction with local ablative therapies to prevent and constantly proactively alter clonal selection. Such an approach would be informed by precision imaging with MRI-brain and FDG-PETs sequentially, and by regular plasma sampling including for circulating tumour DNA sequencing with personalised therapeutic switches occurring prior to the emergence of radiological and clinical relapse. Such an approach to care will require a complete paradigm shift in the way we approach the treatment of advanced cancer, however evidence to date in ALK+ lung cancers, support this new frontier of investigation.
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Affiliation(s)
- Malinda Itchins
- Department of Medical Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, NSW, Australia
- Northern Clinical School, University of Sydney, Kolling Institute, St Leonards, NSW, Australia
- North Shore Health Hub, GenesisCare, St Leonards, NSW, Australia
- *Correspondence: Malinda Itchins,
| | - Nick Pavlakis
- Department of Medical Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, St Leonards, NSW, Australia
- Northern Clinical School, University of Sydney, Kolling Institute, St Leonards, NSW, Australia
- North Shore Health Hub, GenesisCare, St Leonards, NSW, Australia
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31
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Christ SM, Pohl K, Muehlematter UJ, Heesen P, Kühnis A, Willmann J, Ahmadsei M, Badra EV, Kroeze SGC, Mayinger M, Andratschke N, Huellner M, Guckenberger M. Imaging-based prevalence of oligometastatic disease: A single-center cross-sectional study. Int J Radiat Oncol Biol Phys 2022; 114:596-602. [PMID: 35908582 DOI: 10.1016/j.ijrobp.2022.06.100] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2022] [Revised: 05/25/2022] [Accepted: 06/26/2022] [Indexed: 10/31/2022]
Abstract
INTRODUCTION AND BACKGROUND Oligometastatic disease refers to a distinct state in cancer patients characterized by a low metastatic burden, with diagnosis being defined by a limited number of distant metastases in radiological imaging. However, oligometastasis remains poorly understood in terms of its biology and prevalence in the metastatic cascade. In the absence of clinically viable molecular biomarkers, this study examined the prevalence of oligometastasis using oncological imaging. MATERIALS AND METHODS This study is based on all consecutive FDG- and PSMA-PET scans conducted at our cancer center between January and December 2020. We identified and analyzed all PET scans from patients with maximum five distant metastases from a solid malignancy and also reviewed concurrent cMRI imaging in all candidate patients. Data on number and site of metastases were extracted from the imaging reports and verified on imaging studies in case of uncertainties. RESULTS In total, 7,000 PET scans were analyzed, 1,155 of which were performed in unique metastatic patients, and 637 patients showed extra-cranial oligometastatic disease (55%). Concurrent cMRI scans were available for 20% (130/637) of extracranial oligometastatic patients, 36 of which proved to be polymetastatic after combined PET and cMRI analysis. Prevalence of oligometastatic disease was influenced by primary tumor histology and most frequent in pancreatic, liver and gallbladders cancers (59%), and least frequent in cancer of unknown primary (26%). In 72% of oligometastatic cases, only one or two metastases were detected. Bone/soft tissue metastases were the most common sites of distant metastasis (41%). About three quarters of patients had metachronous oligometastatic disease. DISCUSSION AND CONCLUSION Our analysis suggests that about half of metastatic cancer patients are characterized by a limited tumor burden detectable on PET and cMRI imaging. This finding warrants intensified research efforts to better understand the biology of oligometastatic disease and to optimize multidisciplinary treatment strategies.
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Affiliation(s)
- Sebastian M Christ
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
| | | | - Urs J Muehlematter
- Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | | | - Anja Kühnis
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Jonas Willmann
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Maiwand Ahmadsei
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Eugenia Vlaskou Badra
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Stephanie G C Kroeze
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Michael Mayinger
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Nicolaus Andratschke
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Martin Huellner
- Department of Nuclear Medicine, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Matthias Guckenberger
- Department of Radiation Oncology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
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Garde-Noguera J, Martín-Martín M, Obeso A, López-Mata M, Crespo IR, Pelari-Mici L, Juan Vidal O, Mielgo-Rubio X, Trujillo-Reyes JC, Couñago F. Current treatment landscape for oligometastatic non-small cell lung cancer. World J Clin Oncol 2022; 13:485-495. [PMID: 35949432 PMCID: PMC9244972 DOI: 10.5306/wjco.v13.i6.485] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/25/2021] [Revised: 06/24/2021] [Accepted: 05/12/2022] [Indexed: 02/06/2023] Open
Abstract
The management of patients with advanced non-small cell lung carcinoma (NSCLC) has undergone major changes in recent years. On the one hand, improved sensitivity of diagnostic tests, both radiological and endoscopic, has altered the way patients are staged. On the other hand, the arrival of new drugs with antitumoral activity, such as targeted therapies or immunotherapy, has changed the prognosis of patients, improving disease control and prolonging survival. Finally, the development of radiotherapy and surgical and interventional radiology techniques means that radical ablative treatments can be performed on metastases in any location in the body. All of these advances have impacted the treatment of patients with advanced lung cancer, especially in a subgroup of these patients in which all of these treatment modalities converge. This poses a challenge for physicians who must decide upon the best treatment strategy for each patient, without solid evidence for one optimal mode of treatment in this patient population. The aim of this article is to review, from a practical and multidisciplinary perspective, published evidence on the management of oligometastatic NSCLC patients. We evaluate the different alternatives for radical ablative treatments, the role of primary tumor resection or radiation, the impact of systemic treatments, and the therapeutic sequence. In short, the present document aims to provide clinicians with a practical guide for the treatment of oligometastatic patients in routine clinical practice.
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Affiliation(s)
- Javier Garde-Noguera
- Department of Medical Oncology, Hospital Arnau de Vilanova, Valencia 46015, Spain
| | | | - Andres Obeso
- Department of Thoracic Surgery, Hospital Clínico Universitario de Santiago de Compostela, Vigo 15706, Spain
| | - Miriam López-Mata
- Department of Radiation Oncology, Hospital Clínico Universitario Lozano Blesa, Zaragoza 50009, Spain
| | - Inigo Royo Crespo
- Department of Thoracic Surgery, Hospital Universitari Vall d’ Hebron, Barcelona 08035, Spain
| | - Lira Pelari-Mici
- Department of Radiation Oncology, Hospital Universitario Ramón y Cajal, Madrid 28034, Spain
| | - O Juan Vidal
- Department of Medical Oncology, Hospital Universitario y Politécnico La Fe, Valencia 46026, Spain
| | - Xabier Mielgo-Rubio
- Department of Medical Oncology, Hospital Universitario Fundación Alcorcón, Alcorcón 28922, Madrid, Spain
| | - Juan Carlos Trujillo-Reyes
- Department of Thoracic Surgery, Hospital de la Santa Creu I Sant Pau, Barcelona 08029, Spain
- Department of Surgery, Universitat Autonoma de Barcelona, Barcelona 08029, Spain
| | - Felipe Couñago
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Madrid 28223, Spain
- Department of Radiation Oncology, Hospital La Luz, Madrid 28003, Spain
- Medicine Department, School of Biomedical Sciences, Universidad Europea de Madrid, Villaviciosa de Odón 28670, Madrid, Spain
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The Role of Surgery for Oligometastatic Non-Small Cell Lung Cancer. Cancers (Basel) 2022; 14:cancers14102524. [PMID: 35626125 PMCID: PMC9139825 DOI: 10.3390/cancers14102524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Revised: 05/12/2022] [Accepted: 05/12/2022] [Indexed: 11/17/2022] Open
Abstract
Oligometastatic non-small cell lung cancer (NSCLC) is metastatic disease that refers to a limited number of metastatic sites. It is analogous to an intermediate stage of NSCLC, between localized and widely metastatic disease, even though no staging criteria establishes this distinction. Oligometastatic NSCLC describes a patient subgroup with limited metastasis to one or a few organs. These patients seem to have a more indolent cancer than those with diffuse metastasis. For these select patients with oligometastatic disease, the use of palliative systemic therapy over local aggressive treatment may be a missed opportunity to improve survival. The clear definition of this subgroup and identification of the best treatment remains the current challenge in the management of the disease. Surgery was the early cornerstone in the treatment of limited disease; however, as modalities such as chemotherapy, stereotactic radiosurgery, and immunotherapy have matured, the role of excision is less clearly defined. There are sparse randomized controlled trials comparing the efficacy of different treatment modalities in patients with oligometastatic NSCLC. However, there is a growing body of retrospective research detailing the prognostic factors that characterize the role of surgery in the management of these patients. This article clarifies the context and definition of the term oligometastatic, as it applies to NSCLC, and reviews the current results in the use of surgery for its management.
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Milic M, Mondini M, Deutsch E. How to Improve SBRT Outcomes in NSCLC: From Pre-Clinical Modeling to Successful Clinical Translation. Cancers (Basel) 2022; 14:cancers14071705. [PMID: 35406477 PMCID: PMC8997119 DOI: 10.3390/cancers14071705] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Revised: 03/14/2022] [Accepted: 03/22/2022] [Indexed: 02/01/2023] Open
Abstract
Simple Summary Despite major research and clinical efforts, lung cancer remains the leading cause of cancer-related death. Stereotactic body radiotherapy (SBRT) has emerged as a major treatment modality for lung cancer in the last decade. Additional research is needed to elucidate underlying mechanisms of resistance and to develop improved therapeutic strategies. Clinical progress relies on accurate preclinical modelling of human disease in order to yield clinically meaningful results; however, successful translation of pre-clinical research is still lagging behind. In this review, we summarize the major clinical developments of radiation therapy for non-small-cell lung cancer (NSCLC), and we discuss the pre-clinical research models at our disposal, highlighting ongoing translational challenges and future perspectives. Abstract Despite major research and clinical efforts, lung cancer remains the leading cause of cancer-related death. While the delivery of conformal radiotherapy and image guidance of stereotactic body radiotherapy (SBRT) have revolutionized the treatment of early-stage non-small-cell lung cancer (NSCLC), additional research is needed to elucidate underlying mechanisms of resistance and identify novel therapeutic combinations. Clinical progress relies on the successful translation of pre-clinical work, which so far has not always yielded expected results. Improved clinical modelling involves characterizing the preclinical models and selecting appropriate experimental designs that faithfully mimic precise clinical scenarios. Here, we review the current role of SBRT and the scope of pre-clinical armamentarium at our disposal to improve successful clinical translation of pre-clinical research in the radiation oncology of NSCLC.
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Affiliation(s)
- Marina Milic
- Gustave Roussy, Université Paris-Saclay, INSERM U1030, F-94805 Villejuif, France;
| | - Michele Mondini
- Gustave Roussy, Université Paris-Saclay, INSERM U1030, F-94805 Villejuif, France;
- Correspondence: (M.M.); (E.D.)
| | - Eric Deutsch
- Gustave Roussy, Université Paris-Saclay, INSERM U1030, F-94805 Villejuif, France;
- Gustave Roussy, Département d’Oncologie-Radiothérapie, F-94805 Villejuif, France
- Correspondence: (M.M.); (E.D.)
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Badellino S, Levis M, Cuffini EM, Cerrato M, Orlandi E, Chiovatero I, Aprile A, Gastino A, Cavallin C, Iorio GC, Parise R, Mantovani C, Ricardi U. Role of Radiosurgery and Stereotactic Ablative Radiotherapy for Oligometastatic Non-Oncogene Addicted NSCLC. Cancers (Basel) 2022; 14:cancers14061465. [PMID: 35326616 PMCID: PMC8946847 DOI: 10.3390/cancers14061465] [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: 02/11/2022] [Revised: 03/03/2022] [Accepted: 03/11/2022] [Indexed: 12/10/2022] Open
Abstract
Local ablative therapy (LAT), intended as stereotactic ablative radiotherapy or stereotactic radiosurgery, is a well-recognized effective treatment for selected patients with oligometastatic NSCLC. Current clinical evidence supports LAT alone or in combination with systemic therapies. Our retrospective mono-institutional study aims to assess the role of LAT with a peculiar focus on the largest series of non-oncogene addicted oligometastatic NSCLC patients to date. We included in this analysis all patients with the mentioned disease characteristics who underwent LAT for intracranial and/or extracranial metastases between 2011 and 2020. The main endpoints were local control (LC), progression free survival (PFS) and overall survival (OS) in the whole population and after stratification for prognostic factors. We identified a series of 245 consecutive patients (314 lesions), included in this analysis (median age 69 years). In 77% of patients, a single metastasis was treated with LAT and intracranial involvement was the most frequent indication (53% of patients) in our series. The overall response rate (ORR) after LAT was 95%. In case of disease progression, 66 patients underwent new local treatments with curative intent. With a median follow-up of 18 months, median PFS was 13 months (1-year PFS 50%) and median OS was 32 months (1-year OS 75%). The median LC was not reached (1-year LC 89%). The presence of brain metastases was the only factor that negatively affected all clinical endpoints, with a 1-year LC, PFS and OS of 82%, 29% and 62% respectively, compared to 95%, 73% and 91%, respectively, for patients without BMs (p < 0.001 for each endpoint). At the multivariate analysis, mediastinal nodal involvement at baseline (p = 0.049), ECOG PS = 1 (p = 0.011), intracranial disease involvement (p = 0.001), administration of chemotherapy in combination with LAT (p = 0.020), and no delivery of further local treatment for progression or delivery of focal treatment for intracranial progression (p < 0.001) were related to a poorer OS. In our retrospective series, which is to our knowledge the largest to date, LAT showed encouraging results and confirmed the safety and effectiveness of focal treatments in non-oncogene addicted oligometastatic NSCLC patients.
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Chen YH, Ho UC, Kuo LT. Oligometastatic Disease in Non-Small-Cell Lung Cancer: An Update. Cancers (Basel) 2022; 14:cancers14051350. [PMID: 35267658 PMCID: PMC8909159 DOI: 10.3390/cancers14051350] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2022] [Revised: 02/11/2022] [Accepted: 03/02/2022] [Indexed: 01/27/2023] Open
Abstract
Simple Summary Approximately 7–50% of patients with non-small-cell lung cancer (NSCLC) develop oligometastases, which are new tumors found in another part of the body, arising from cancer cells of the original tumor that have travelled through the body. In recent years, these patients have been increasingly regarded as a distinct group that could benefit from treatment that intends to cure the disease, rather than palliative care, to achieve a better clinical outcome. Various treatment procedures have been developed for treating NSCLC patients with different oligometastatic sites. In addition, the newly proposed uniform definition for oligometastases as well as ongoing trials may lead to increased appropriate patient selection and evaluation of treatment effectiveness. The aim of this review article is to summarize the latest evidence regarding optimal management strategies for NSCLC patients with oligometastases. Abstract Oligometastatic non-small-cell lung cancer (NSCLC) is a distinct entity that is different from localized and disseminated diseases. The definition of oligometastatic NSCLC varies across studies in past decades owing to the use of different imaging modalities; however, a uniform definition of oligometastatic NSCLC has been proposed, and this may facilitate trial design and evaluation of certain interventions. Patients with oligometastatic NSCLC are candidates for curative-intent management, in which local ablative treatment, such as surgery or stereotactic radiosurgery, should be instituted to improve clinical outcomes. Although current guidelines recommend that local therapy for thoracic and metastatic lesions should be considered for patients with oligometastatic NSCLC with stable disease after systemic therapy, optimal management strategies for different oligometastatic sites have not been established. Additionally, the development of personalized therapies for individual patients with oligometastatic NSCLC to improve their quality of life and overall survival should also be addressed. Here, we review relevant articles on the management of patients with oligometastatic NSCLC and categorize the disease according to the site of metastases. Ongoing trials are also summarized to determine future directions and expectations for new treatment modalities to improve patient management.
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Affiliation(s)
- Yi-Hsing Chen
- Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital Yunlin Branch, Douliu 640, Taiwan; (Y.-H.C.); (U.-C.H.)
| | - Ue-Cheung Ho
- Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital Yunlin Branch, Douliu 640, Taiwan; (Y.-H.C.); (U.-C.H.)
| | - Lu-Ting Kuo
- Division of Neurosurgery, Department of Surgery, National Taiwan University Hospital, Taipei 100, Taiwan
- Correspondence: ; Tel.: +886-2-2312-3456
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Li X, Wang J, Chang X, Gao Z, Teng F, Meng X, Yu J. Optimal Initial Time Point of Local Radiotherapy for Unresectable Lung Adenocarcinoma: A Retrospective Analysis on Overall Arrangement of Local Radiotherapy in Advanced Lung Adenocarcinoma. Front Oncol 2022; 12:793190. [PMID: 35223474 PMCID: PMC8867094 DOI: 10.3389/fonc.2022.793190] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 01/17/2022] [Indexed: 11/13/2022] Open
Abstract
Local radiotherapy (LRT) is reported to be of survival benefit for advanced non-small cell lung cancer (NSCLC) in accumulating evidence, but research on the optimal initial time point remains scarce. This IRB-approved retrospective analysis identified patients diagnosed with stage IIIb–IV unresectable lung adenocarcinoma who initiated front-line LRT at our institution between 2017 and 2020. The receiver operating characteristic (ROC) curve analyses were used to cut off the initial time of LRT (before and beyond 53 days). Patients were divided into two groups: one early to initiate radiotherapy group (≤53 days, EAR group) and one deferred radiotherapy group (>53 days, DEF group). The Kaplan–Meier method was used to estimate time-to-event endpoints; the Cox proportional hazard model was used to find out predictors of progression-free survival (PFS) and overall survival (OS). A total of 265 patients with a median age of 57 were enrolled. The median follow-up time was 26.4 months (ranging from 2.2 to 69.7 months). The mOS was 38.6 months and mPFS was 12.7 months. Age >60, bone and brain metastases, multisite metastases, and EGFR 19 mutation were independent predictors associated with OS. Early initiation of local radiotherapy within 53 days after diagnosis resulted in better PFS, but not in OS. A better OS was observed in patients with bone metastasis who underwent local radiotherapy initiated within 53 days.
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Affiliation(s)
- Xinge Li
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China.,Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Jie Wang
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China
| | - Xu Chang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Zhenhua Gao
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.,Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Feifei Teng
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Xue Meng
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Jinming Yu
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, China.,Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
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Pasquini G, Menichelli C, Pastore G, Casamassima F, Fabrini MG, Cappelli S, Valleggi S, Lucchesi M, Lucchi M, Ricciardi R, Maestri M, Guida M, Chella A, Petrini I. Stereotactic body radiation therapy for the treatment of pleural metastases in patients with thymoma: a retrospective review of 22 patients. J Thorac Dis 2022; 13:6373-6380. [PMID: 34992817 PMCID: PMC8662497 DOI: 10.21037/jtd-19-3799] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2019] [Accepted: 03/18/2020] [Indexed: 11/06/2022]
Abstract
Background Thymomas can benefit of cytoreductive surgery even if a complete resection is not feasible. The pleural cavity is the most common site of progression and the resection of pleural metastases can be performed in selected patients. We evaluated the results of stereotactic body radiation therapy for the treatment of pleural metastases in patients not eligible for surgery. Methods We retrospectively selected 22 patients treated with stereotactic body radiation therapy for pleural metastases between 2013 and 2019. According to RECIST criteria 1.1 modified for thymic epithelial tumors, time to local failure and progression free survival were calculated using Kaplan-Meier method. Results The median age was 40 years (range, 29-73 years). There were 1 A, 3 AB, 3 B1, 3 B2, 3 B2/B3 and 9 B3 thymomas. Pleural metastases and primary tumor were synchronous in 8 patients. Five patients had a single pleural metastatic site and 17 presented multiple localizations. Sixteen patients received stereotactic body radiation therapy on multiple sites of pleural metastases. The median dose of radiation was 30 Gy (range, 24-40 Gy). With a median follow-up of 33.2 months (95% CI: 13.1-53.3 months), ten patients experienced disease progression with a median progression free survival was 20.4 months (95% CI: 10.7-30.0 months). The disease control rate was 79% and 41% after 1 and 2 years, respectively. Local disease control rate was 92% and 78% after 1 and 2 years, respectively. There were not significant differences in progression free survival between patients diagnosed with synchronous and metachronous metastases (P=0.477), across those treated or not with chemotherapy (P=0.189) and between those who received or not a previous surgical resection of the pleural metastases (P=0.871). There were not grade 3-4 toxicities related to the treatment. Conclusions Stereotactic body radiation therapy of pleural metastases is feasible and offers a promising local control of diseases. The impact of this treatment on patients' survival is hardly predictable because of the heterogeneous clinical behavior of thymomas.
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Affiliation(s)
- Giulia Pasquini
- Medical Oncology, Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
| | - Claudia Menichelli
- Department of Radiotherapy, Institute of Clinical Research Ecomedica, Empoli, Italy
| | - Gabriella Pastore
- Department of Medical Physics, Institute of Clinical Research Ecomedica, Empoli, Italy
| | - Franco Casamassima
- Department of Radiotherapy, Institute of Clinical Research Ecomedica, Empoli, Italy
| | | | | | | | | | - Marco Lucchi
- Thoracic Surgery, Department of Surgical Pathology, Molecular Medicine and Critical Area, University Hospital of Pisa, Pisa, Italy
| | - Roberta Ricciardi
- Neurology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy
| | - Michelangelo Maestri
- Neurology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy
| | - Melania Guida
- Neurology Unit, Department of Clinical and Experimental Medicine, University Hospital of Pisa, Pisa, Italy
| | - Antonio Chella
- Pneumology Unit, University Hospital of Pisa, Pisa, Italy
| | - Iacopo Petrini
- General Pathology, Department of Translational Research and New Technology in Medicine and Surgery, University of Pisa, Pisa, Italy
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Patient Selection for Local Aggressive Treatment in Oligometastatic Non-Small Cell Lung Cancer. Cancers (Basel) 2021; 13:cancers13246374. [PMID: 34944994 PMCID: PMC8699700 DOI: 10.3390/cancers13246374] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/12/2021] [Accepted: 12/14/2021] [Indexed: 12/20/2022] Open
Abstract
Simple Summary Since the first introduction of the oligometastatic state with a low burden of metastases in non-small cell lung cancer, accumulating evidence from retrospective and prospective studies has shown that a local aggressive, multimodality treatment may significantly improve the prognosis in these patients. Local aggressive treatment includes a systemic therapy of micrometastatic disease, as well as a radical resection of the primary tumor and surgical resection and/or radiation therapy of distant metastases. However, patient selection and treatment allocation remain a central challenge in oligometastatic disease. In this review, we aimed to address the current evidence on criteria for patient selection for local aggressive treatment in non-small cell lung cancer. Abstract One-fourth of all patients with metastatic non-small cell lung cancer presents with a limited number of metastases and relatively low systemic tumor burden. This oligometastatic state with limited systemic tumor burden may be associated with remarkably improved overall and progression-free survival if both primary tumor and metastases are treated radically combined with systemic therapy. This local aggressive therapy (LAT) requires a multidisciplinary approach including medical oncologists, radiation therapists, and thoracic surgeons. A surgical resection of the often advanced primary tumor should be part of the radical treatment whenever feasible. However, patient selection, timing, and a correct treatment allocation for LAT appear to be essential. In this review, we aimed to summarize and discuss the current evidence on patient selection criteria such as characteristics of the primary tumor and metastases, response to neoadjuvant or first-line treatment, molecular characteristics, mediastinal lymph node involvement, and other factors for LAT in oligometastatic NSCLC.
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Myall NJ, Yu H, Soltys SG, Wakelee HA, Pollom E. Management of brain metastases in lung cancer: evolving roles for radiation and systemic treatment in the era of targeted and immune therapies. Neurooncol Adv 2021; 3:v52-v62. [PMID: 34859233 PMCID: PMC8633733 DOI: 10.1093/noajnl/vdab106] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Brain metastases are a common occurrence in both non-small cell and small cell lung cancer with the potential to affect quality of life and prognosis. Due to concerns about the accessibility of the central nervous system by systemic chemotherapy agents, the management of brain metastases has historically relied on local therapies including surgery and radiation. However, novel targeted and immune therapies that improve overall outcomes in lung cancer have demonstrated effective intracranial activity. As a result, the management of brain metastases in lung cancer has evolved, with both local and systemic therapies now playing an important role. Factors such as tumor histology (non-small versus small cell), oncogenic driver mutations, and symptom burden from intracranial disease impact treatment decisions. Here, we review the current management of brain metastases in lung cancer, highlighting the roles of stereotactic radiosurgery and novel systemic therapies as well as the ongoing questions that remain under investigation.
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Affiliation(s)
- Nathaniel J Myall
- Division of Oncology, Department of Medicine, Stanford Cancer Institute, Palo Alto, California, USA
| | - Helena Yu
- Department of Medicine-Oncology, Memorial Sloan Kettering Cancer Center, New York City, New York, USA
| | - Scott G Soltys
- Department of Radiation Oncology, Stanford Cancer Institute, Palo Alto, California, USA
| | - Heather A Wakelee
- Division of Oncology, Department of Medicine, Stanford Cancer Institute, Palo Alto, California, USA
| | - Erqi Pollom
- Department of Radiation Oncology, Stanford Cancer Institute, Palo Alto, California, USA
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Zhang C, Ma N, Zhang Q, Zheng K, Sun C, Tang X, Li X, Zhao J. Evaluation of local aggressive lung therapy versus systemic therapy in oligometastatic non-small cell lung cancer: a systematic review and meta-analysis. J Thorac Dis 2021; 13:5899-5910. [PMID: 34795938 PMCID: PMC8575811 DOI: 10.21037/jtd-21-957] [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: 06/09/2021] [Accepted: 08/13/2021] [Indexed: 11/06/2022]
Abstract
Background Previous studies have shown the feasibility and effectiveness of local aggressive thoracic therapy (surgery and radiotherapy) for oligometastatic non-small cell lung cancer compared with systemic therapy, but with small sample. This study aims to perform a pooled analysis to explore whether LT could improve outcomes of oligometastatic patients with non-small cell lung cancer. Methods Protocol of present study was registered on PROSPERO as number: CRD42021233095. PubMed, Embase and Web of knowledge were searched, and eligible studies investigating local therapy for non-small cell lung cancer with 1-5 metastases regardless of organs were included. Linear regression between survival and clinical characteristics were conducted. Hazard ratios of survival and adverse effects were merged. Pooled survival curves were carried out. Results Three randomized controlled trials and 5 cohort studies enrolling 499 patients were included. There was a trend that median overall survival declined with the increasing proportion of N2-3 positive patients in local therapy group, but with no statistical difference (P=0.09, R2=0.98). Undergoing local therapy for oligometastatic non-small cell lung cancer achieved reduction of 47% and 60% in the risk of death and cancer progression (P<0.001), respectively. In subgroup analysis, patients receiving local therapy including surgery showed hazard ratio of 0.33 on progression-free survival and 0.55 of these excluding surgery. Patients receiving consolidative local therapy (local therapy after systemic therapy) obtained hazard ratios 0.33 and 0.45 on progression-free and overall survival vs. systemic therapy, respectively. Hazard ratios of those receiving upfront local therapy (local therapy first) were 0.62 and 0.68 on progression-free and overall survival vs. systemic therapy. Pooled survival analysis showed median overall and progression-free survival of local therapy (21.6 and 14 months) group were both longer than systemic one (14.3 and 6.5 months). Odds ratio of adverse effects were no difference between 2 groups (P=0.16). Conclusions Local aggressive thoracic therapy could prolong 7 months overall and progression-free survival compared with systemic therapy in patients with oligometastatic non-small cell lung cancer. Consolidative local therapy might be a more favorable choice of local therapy. Benefits of local therapy for N2-3 positive patients should explored further.
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Affiliation(s)
- Chenxi Zhang
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Nan Ma
- Department of Ophthalmology, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Qitong Zhang
- School of Stomatology, Xi'an Medical University, Xi'an, China
| | - Kaifu Zheng
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Chuang Sun
- Department of Cardiology, Xi'an International Medical Center Hospital, Xi'an, China
| | - Xiyang Tang
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Xiaofei Li
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
| | - Jinbo Zhao
- Department of Thoracic Surgery, Tangdu Hospital, Air Force Medical University, Xi'an, China
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Results of Radiation Therapy as Local Ablative Therapy for Oligometastatic Non-Small Cell Lung Cancer. Cancers (Basel) 2021; 13:cancers13225773. [PMID: 34830925 PMCID: PMC8616303 DOI: 10.3390/cancers13225773] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 11/15/2021] [Accepted: 11/16/2021] [Indexed: 11/16/2022] Open
Abstract
Oligometastatic cancer is characterized by a limited number of metastatic deposits. Compared with lung cancer patients who have more widespread disease, oligometastatic lung cancer patients have more favorable survival outcomes. Therefore, it has been hypothesized that local ablative therapy (LAT) directed at the metastatic deposits in addition to standard-of-care systemic therapy may further improve survival outcomes in oligometastatic lung cancer patients. One LAT modality that has been utilized in oligometastatic lung cancer is radiation therapy. In particular, ultra-hypofractionated radiotherapy, also known as stereotactic body radiotherapy (SBRT), has been shown to provide excellent local control with a favorable safety profile. Here, we reviewed the retrospective studies and prospective trials that have deployed radiation therapy as LAT in oligometastatic lung cancer, including randomized studies showing benefits for progression-free survival and overall survival with the addition of LAT. We also discuss the impact of targeted therapies and immunotherapy on radiation as LAT.
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Amini A, Verma V, Simone CB, Chetty IJ, Chun SG, Donington J, Edelman MJ, Higgins KA, Kestin LL, Movsas B, Rodrigues GB, Rosenzweig KE, Rybkin II, Slotman BJ, Wolf A, Chang JY. American Radium Society Appropriate Use Criteria for Radiation Therapy in Oligometastatic or Oligoprogressive Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys 2021; 112:361-375. [PMID: 34571054 DOI: 10.1016/j.ijrobp.2021.09.022] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 09/02/2021] [Accepted: 09/10/2021] [Indexed: 12/25/2022]
Abstract
PURPOSE Recent randomized studies have suggested improvements in progression-free and overall survival with the addition of stereotactic body radiation therapy (SBRT, also known as SABR) in patients with oligometastatic non-small cell lung cancer. Given the novelty and complexity of incorporating SBRT in the oligometastatic setting, the multidisciplinary American Radium Society Lung Cancer Panel was assigned to create appropriate use criteria on SBRT as part of consolidative local therapy for patients with oligometastatic and oligoprogressive non-small cell lung cancer. METHODS AND MATERIALS A review of the current literature was conducted from January 1, 2008, to December 25, 2020, using the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines to systematically search the PubMed database to retrieve a comprehensive set of relevant articles. RESULTS Based on representation in existing randomized trials, the panel defined the term "oligometastasis" as ≤3 metastatic deposits (not including the primary tumor) in the previously untreated setting or after first-line systemic therapy after the initial diagnosis. "Oligoprogression" also referred to ≤3 discrete areas of progression in the setting of prior or ongoing receipt of systemic therapy. In all appropriate patients, the panel strongly recommends enrollment in a clinical trial whenever available. For oligometastatic disease, administering first-line systemic therapy followed by consolidative radiation therapy (to all sites plus the primary/nodal disease) is preferred over up-front radiation therapy. Owing to a dearth of data, the panel recommended that consolidative radiation therapy be considered on a case-by-case basis for 4 to 5 sites of oligometastatic disease, driver mutation-positive oligometastatic disease without progression on up-front targeted therapy, and oligoprogressive cases. CONCLUSIONS Although SBRT/SABR appears to be both safe and effective in treating patients with limited metastatic sites of disease, many clinical circumstances require individualized management and strong multidisciplinary discussion on account of the limited existing data.
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Affiliation(s)
- Arya Amini
- City of Hope National Medical Center, Duarte, California.
| | - Vivek Verma
- The University of Texas, M.D. Anderson Cancer Center, Houston, Texas
| | - Charles B Simone
- New York Proton Center, New York, New York; Memorial Sloan Kettering Cancer Center, New York, New York
| | | | - Stephen G Chun
- The University of Texas, M.D. Anderson Cancer Center, Houston, Texas
| | | | - Martin J Edelman
- Fox Chase Comprehensive Cancer Center, Philadelphia, Pennsylvania
| | | | | | | | | | | | | | - Benjamin J Slotman
- Amsterdam University Medical Center, De Boelelaan, Amsterdam, The Netherlands
| | - Andrea Wolf
- Mount Sinai School of Medicine, New York, New York
| | - Joe Y Chang
- The University of Texas, M.D. Anderson Cancer Center, Houston, Texas
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Wang F, Gao J, Ren Y, Su H, She Y, Xie D, Chen C. Predicted outcomes of subdividing M1-stage metastatic lung cancer based on the prognosis and the response to local consolidative therapy. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:1293. [PMID: 34532430 PMCID: PMC8422121 DOI: 10.21037/atm-21-1383] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 07/01/2021] [Indexed: 11/06/2022]
Abstract
Background For stage IV non-small cell lung cancer (NSCLC) patients, systemic therapy is the main strategy, and local consolidative therapy tends to be performed for patients with oligometastases. The porpose of this article is to evaluate the prognostic effects of local consolidative therapy for patients with stage IV NSCLC and divide these patients into different subcategories to stratify the prognoses. Methods A total of 30,583 patients with stage IV NSCLC were identified in the Surveillance, Epidemiology, and End Results (SEER) database. To identify factors related to high cancer-specific mortality (CSM) rates and compare the prognostic effects of different treatment strategies, a competing risk model was developed. Furthermore, independent prognostic factors identified through multivariable analysis were employed to supplement the current M1 subcategory. Cumulative incidence curves were estimated using the Kaplan-Meier method, and the log-rank test was used to compare prognostic differences. Results The CSM rates of M1a, M1b, and M1c patients were significantly different [M1b versus M1a: subdistribution hazard ratio (SHR), 1.38; 95% confidence interval (CI), 1.31-1.45; P<0.001; M1c vs. M1a: SHR, 1.76; 95% CI, 1.67-1.85; P<0.001]. Patients were divided into five groups depending on the M1 subcategory and liver involvement (Group A, M1c NSCLC with liver involvement; Group B, M1c NSCLC without liver involvement; Group C, M1b NSCLC with liver involvement; Group D, M1b NSCLC without liver involvement; and Group E, M1a NSCLC). Univariable analysis showed that liver involvement was associated with increased cancer-specific mortality (CSM) rates in both M1b and M1c patients (A vs. B: SHR, 1.36; 95% CI, 1.30-1.43; P<0.001; C vs. D: SHR, 1.27; 95% CI, 1.20-1.35; P<0.001). Primary tumor surgery plus chemotherapy may substantially benefit patients, especially M1b patients (surgery alone: SHR, 0.425; 95% CI, 0.361-0.500; P<0.001 vs. chemotherapy alone: SHR, 0.366; 95% CI, 0.352-0.382; P<0.001 vs. chemotherapy plus surgery: SHR, 0.194; 95% CI, 0.165-0.228; P<0.001; no treatment used as reference). Conclusions Subdivision of M1 disease and awareness of liver involvement may help to inform the prognosis of stage IV NSCLC patients and facilitate treatment planning.
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Affiliation(s)
- Fang Wang
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Jiani Gao
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yijiu Ren
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Hang Su
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Yunlang She
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Dong Xie
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
| | - Chang Chen
- Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China
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Chao C, Qian Y, Li X, Sang C, Wang B, Zhang XY. Surgical Survival Benefits With Different Metastatic Patterns for Stage IV Extrathoracic Metastatic Non-Small Cell Lung Cancer: A SEER-Based Study. Technol Cancer Res Treat 2021; 20:15330338211033064. [PMID: 34496678 PMCID: PMC8442485 DOI: 10.1177/15330338211033064] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
Background: With the knowledge of oligometastases, primary surgery plays an increasingly
vital role in metastatic non-small cell lung cancer. We aimed to evaluate
the survival benefit of primary surgery based on metastatic patterns. Materials and Methods: The selected patients with stage IV extrathoracic metastatic (m1b) non-small
cell lung cancer between 2010 and 2015 were included in a retrospective
cohort study from the Surveillance, Epidemiology, and End Results (SEER)
database. Multiple imputation was used for the missing data. Patients were
divided into 2 groups depending on whether surgery was performed. After
covariate balancing propensity score (CBPS) weighting, multivariate Cox
regression models and Kaplan-Meier survival curve were built to identify the
survival benefit of different metastatic patterns. Results: Surgery can potentially increase the overall survival (OS) (adjusted HR:
0.68, P < 0.001) of non-small cell lung cancer. The
weighted 3-year OS in the surgical group was 16.9%, compared with 7.8% in
the nonsurgical group. For single organ metastasis, surgery could improve
the survival of metastatic non-small cell lung cancer. Meanwhile, no
significant survival improvements in surgical group were observed in
patients with multiple organ metastases. Conclusion: The surgical survival benefits for extrathoracic metastatic non-small cell
lung cancer could be divided by metastatic pattern.
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Affiliation(s)
- Ce Chao
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Yongxiang Qian
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Xihao Li
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Chen Sang
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Bin Wang
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
| | - Xiao-Ying Zhang
- Department of Cardiothoracic Surgery, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu, China
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Liu B, Liu H, Ma Y, Ding Q, Zhang M, Liu X, Liu M. EGFR-mutated stage IV non-small cell lung cancer: What is the role of radiotherapy combined with TKI? Cancer Med 2021; 10:6167-6188. [PMID: 34374490 PMCID: PMC8446557 DOI: 10.1002/cam4.4192] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2021] [Revised: 07/20/2021] [Accepted: 07/20/2021] [Indexed: 12/17/2022] Open
Abstract
Lung cancer is the leading cause of cancer-related death globally and poses a considerable threat to public health. Asia has the highest prevalence of epidermal growth factor receptor (EGFR) mutations in patients with non-small cell lung cancer (NSCLC). Despite the reasonable response and prolonged survival associated with EGFR-tyrosine kinase inhibitor (TKI) therapy, the acquisition of resistance to TKIs remains a major challenge. Additionally, patients with EGFR mutations are at a substantially higher risk of brain metastasis compared with those harboring wild-type EGFR. The role of radiotherapy (RT) in EGFR-mutated (EGFRm) stage IV NSCLC requires clarification, especially with the advent of next-generation TKIs, which are more potent and exhibit greater central nervous system activity. In particular, the feasible application of RT, including the timing, site, dose, fraction, and combination with TKI, merits further investigation. This review focuses on these key issues, and provides a flow diagram with proposed treatment options for metastatic EGFRm NSCLC, aiming to provide guidance for clinical practice.
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Affiliation(s)
- Bailong Liu
- Department of Radiation OncologyThe First Hospital of Jilin UniversityChangchunChina
| | - Hui Liu
- Department of Radiation OncologyThe First Hospital of Jilin UniversityChangchunChina
| | - Yunfei Ma
- Department of Radiation OncologyThe First Hospital of Jilin UniversityChangchunChina
| | - Qiuhui Ding
- Department of Radiation OncologyThe First Hospital of Jilin UniversityChangchunChina
| | - Min Zhang
- Department of Radiation OncologyThe First Hospital of Jilin UniversityChangchunChina
| | - Xinliang Liu
- Department of Radiation OncologyThe First Hospital of Jilin UniversityChangchunChina
| | - Min Liu
- Department of Radiation OncologyThe First Hospital of Jilin UniversityChangchunChina
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47
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Sundahl N, Lievens Y. Radiotherapy for oligometastatic non-small cell lung cancer: a narrative review. Transl Lung Cancer Res 2021; 10:3420-3431. [PMID: 34430377 PMCID: PMC8350107 DOI: 10.21037/tlcr-20-1051] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Accepted: 03/17/2021] [Indexed: 12/25/2022]
Abstract
Preclinical and early clinical evidence suggest that radical radiotherapy of oligometastatic disease in non-small cell lung cancer (NSCLC) patients can impact outcomes with relatively limited toxicity. Whilst data from phase 2 randomized trials suggesting an improved overall survival (OS) with this treatment is promising, it has also illustrated the heterogeneity in this patient population and treatment. Oligometastatic disease in itself comprises a broad spectrum of patients, in terms of tumor load and location, stage of the disease and treatment history. This real-life variety in patient characteristics is often reflected in studies to a certain extent, hinting to the fact that all might benefit from radical radiotherapy to limited metastatic disease, yet leaving the question unanswered as to whom the ideal candidate is. Furthermore, differences between and within studies with regards to treatment modality, timing, radiation technique, and radiation dose are substantial. Also, preclinical and early clinical trials suggest that radiotherapy can work synergistically with checkpoint inhibitors by acting as an in situ cancer vaccine, therefore the combination of these two treatments in oligometastatic patients might entail the largest benefit. Ongoing randomized controlled phase 3 trials and prospective registry trials will further elucidate the true extent of benefit of this local treatment strategy and aid in identifying the ideal patient population and therapy. The current narrative review summarizes the clinical evidence on radiotherapy for oligometastatic NSCLC and highlights the remaining unknowns.
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Affiliation(s)
- Nora Sundahl
- Department of Radiation Oncology, Ghent University Hospital & Ghent University, Ghent, Belgium
| | - Yolande Lievens
- Department of Radiation Oncology, Ghent University Hospital & Ghent University, Ghent, Belgium
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48
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Gobbini E, Bertolaccini L, Giaj-Levra N, Menis J, Giaj-Levra M. Epidemiology of oligometastatic non-small cell lung cancer: results from a systematic review and pooled analysis. Transl Lung Cancer Res 2021; 10:3339-3350. [PMID: 34430371 PMCID: PMC8350077 DOI: 10.21037/tlcr-20-982] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Accepted: 07/07/2021] [Indexed: 12/25/2022]
Abstract
Background To describe the incidence and the clinical characteristics of oligometastatic non-small cell lung cancer (NSCLC) patients. Oligometastatic NSCLC is gaining recognition as a clinical condition with a different prognosis compared to multi metastatic disease. Usually, four different scenarios of oligometastatic disease can be described but not epidemiological data are available. To date, it is difficult to delineate an exhaustive epidemiological scenario because no uniform or shared definition of oligometastatic status exists, even though a recent consensus defined synchronous oligometastatic disease as having a maximum of 5 metastases in 3 different organs. Methods A systematic review and a pooled analysis of literature were performed. Article selection was based on the following characteristics: focus on lung cancers; dealing with oligometastatic settings and providing a definition of oligometastatic disease; number of metastatic lesions with or without the number of organs involved; providing some incidence or clinical characteristics of oligometastatic NSCLC patients. Series focusing on a specific single metastatic organ were excluded. The research was launched in MEDLINE (OvidSP) in March 2020. Full articles were individually and collectively read by the authors according to the previous criteria. Each author inspected the reference list included in the eligible articles. If the selection criteria were recognized, the article was reviewed by all authors and then included. Data on patient clinical features were pooled together from 31 articles selected. Results A total number of 31 articles have been selected for the analysis. The following variables were extracted from the publications: (I) number of metastases, (II) number of organs involved, (III) number of patients, (IV) number and percentage of males and females, (V) number and percentage of squamous and non-squamous histology, (VI) T and N status and/or stage of primary disease for oligometastatic setting. The data collected have been analyzed according to the oligometastatic setting. Conclusions Oligometastatic status is globally identified as a different clinical condition from multi metastatic NSCLC, although the clinical characteristics were consistent in the general metastatic population, even with a lower-than-expected TN status. The brain and bones were the most frequent organs involved. Lacking consensus definition, these results must be interpreted cautiously and a prospective evaluation is urgently needed.
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Affiliation(s)
- Elisa Gobbini
- Cancer Research Center Lyon, Center Léon Bérard, Lyon, France.,Thoracic Oncology Unit, Grenoble University Hospital, Grenoble, France
| | - Luca Bertolaccini
- Division of Thoracic Surgery, IEO, European Institute of Oncology IRCCS, Milan, Italy
| | - Niccolò Giaj-Levra
- Department of Advanced Radiation Oncology, IRCCS Sacro Cuore Don Calabria Hospital, Negrar di Valpolicella, Italy
| | - Jessica Menis
- Section of Oncology, Department of Medicine, University of Verona Hospital Trust, Verona, Italy
| | - Matteo Giaj-Levra
- Thoracic Oncology Unit, Grenoble University Hospital, Grenoble, France.,Institute for Advanced Biosciences INSERM U1209 CNRS UMR5309, Université Grenoble Alpes, France
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Brandão M, Durieux V, Berghmans T. Current and future research efforts in oligometastatic non-small cell lung cancer-a systematic review. Transl Lung Cancer Res 2021; 10:3473-3485. [PMID: 34430381 PMCID: PMC8350078 DOI: 10.21037/tlcr-20-964] [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: 08/20/2020] [Accepted: 05/17/2021] [Indexed: 01/09/2023]
Abstract
BACKGROUND Major progresses in the systemic treatment of non-small cell lung cancer (NSCLC) were obtained during the last decade, including the use of immunotherapy and tyrosine kinase inhibitors (TKIs), with impressive results in terms of response and survival rates. Moreover, novel imaging and radiotherapy techniques have allowed the development of stereotactic body radiotherapy (SBRT), with high rates of local disease control and minimal toxicity. These factors propelled the use of combined systemic and local treatment strategies in patients with a low burden of metastases-the oligometastatic disease (OMD). METHODS We systematically review the evidence from prospective randomized and non-randomized trials on local ablative therapy for OMD NSCLC published until June 2020. In addition, we present a review of the ongoing and/or recruiting trials in the field. RESULTS We included 16 articles, reporting on 14 prospective clinical trials, starting from the pilot trial conducted in the early 2000's to the recent randomized trials that have showed benefits in survival. We found 24 ongoing trials, which combine multiple local ablative regimens with new systemic therapies, such as new generation TKIs and immunotherapy. DISCUSSION Despite these vast current and ongoing prospective research efforts, there are several issues that impair the generalizability of their findings. These include the heterogeneous definition of OMD, trial design, staging, patient selection, tumor mutational status and treatments used, which may limit their applicability in the clinical practice.
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Affiliation(s)
- Mariana Brandão
- Clinic of Thoracic Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Valérie Durieux
- Bibliothèque des Sciences de la Santé, Université Libre de Bruxelles, Brussels, Belgium
| | - Thierry Berghmans
- Clinic of Thoracic Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
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Tchelebi LT, Goodman KA. Mature Experiences Using Local Therapy for Oligometastases. Semin Radiat Oncol 2021; 31:180-185. [PMID: 34090644 DOI: 10.1016/j.semradonc.2021.02.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Cancer is a heterogeneous disease, consisting of a spectrum of disorders ranging from local-only disease to those that are widely metastatic from their onset. The oligometastatic state, in which tumors harbor a limited number of metastases, may be curable in a subset of patients. The early success of surgical resection of hepatic metastases from colorectal cancer led to investigations into metastatectomy of other sites and, more recently, into the use of stereotactic ablative radiotherapy (SABR) for oligometastatic disease. This article reviews the data establishing the role of surgery for managing limited metastatic disease. Further, we review recent experiences using alternative local therapies, such as SABR, for oligometastases. This review also discusses ongoing trials evaluating local therapies for patients with a limited burden of metastatic cancer.
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Affiliation(s)
- Leila T Tchelebi
- Department of Radiation Oncology, Penn State College of Medicine, Hershey, PA.
| | - Karyn A Goodman
- Department of Radiation Oncology, Icahn School of Medicine at Mount Sinai, New York, NY
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