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Zhou S, Zhai W, Zhang Q, Li H, Fan Y. Impact of prophylactic cranial irradiation on survival in extensive-stage small cell lung cancer receiving first-line chemoimmunotherapy: a propensity score-matched study. Ther Adv Med Oncol 2025; 17:17588359251341158. [PMID: 40415872 PMCID: PMC12102569 DOI: 10.1177/17588359251341158] [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: 02/05/2025] [Accepted: 04/23/2025] [Indexed: 05/27/2025] Open
Abstract
Background Chemoimmunotherapy has emerged as the standard first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), improving survival outcomes. However, the role of prophylactic cranial irradiation (PCI) in the context of chemoimmunotherapy remains undefined. Objectives This study aimed to evaluate the impact of PCI on overall survival (OS) in patients with ES-SCLC after chemoimmunotherapy administration. Design Retrospective study. Methods This retrospective analysis included 261 patients with ES-SCLC treated with first-line chemoimmunotherapy between January 2019 and December 2023. All patients underwent MRI scans to confirm the absence of brain metastases. After 1:2 propensity score matching (PSM), 46 and 81 patients were assigned to the PCI and observation groups, respectively. The primary endpoint was OS, with additional exploration of progression-free survival (PFS), the cumulative incidence of intracranial metastases, and intracranial progression-free survival (iPFS). Results After PSM, the two groups were well-balanced in baseline characteristics. Survival analysis showed a median OS of 19.9 months (95% confidence interval (CI): 11.8-28.0) in the PCI group and 15.6 months (12.3-18.9) in the observation group, without a significant difference (hazard ratio (HR) = 0.763 (95% CI: 0.484-1.206), log-rank p = 0.265). PCI significantly reduced the risk of brain metastasis (Fine-Gray p = 0.002), with 1-year cumulative incidence rates of 13.8% (3.4%-24.2%) in the PCI group and 53.4% (41.3%-65.6%) in the observation group. Subgroup analysis showed that for ES-SCLC patients achieving a partial response to initial chemoimmunotherapy, the PCI group had longer median OS (25.7 months (95% CI: 15.4-36.1) vs 19.4 months (15.4-23.4); HR = 0.502 (0.284-0.886); log-rank p = 0.021). Conclusion PCI did not improve OS in ES-SCLC patients receiving first-line chemoimmunotherapy, while it may confer a survival benefit for patients who achieve remission following chemoimmunotherapy. In addition, PCI significantly reduced the incidence of brain metastases. These findings warrant further randomized studies for verification.
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Affiliation(s)
- Shichao Zhou
- Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, China
| | - Wanchen Zhai
- Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, China
- Department of Oncology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Qian Zhang
- Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, Hangzhou, Zhejiang, China
- Department of Oncology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Hui Li
- Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, No. 1 East Banshan Road, Gongshu District, Hangzhou, Zhejiang 310022, China
| | - Yun Fan
- Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou Institute of Medicine, Chinese Academy of Sciences, No. 1 East Banshan Road, Gongshu District, Hangzhou, Zhejiang 310022, China
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Zhan TY, Deng L, Wang WQ, Zhang T, Wang JY, Wang X, Liu WY, Zhai YR, Xiao ZF, Feng QF, Bi N, Li YX, Zhou ZM. Implementing the optimized hippo-avoidance prophylactic cranial irradiation for limited-stage small cell lung cancer by tomotherapy and volumetric modulated arc therapy. Thorac Cancer 2024. [PMID: 39440477 DOI: 10.1111/1759-7714.15462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2024] [Revised: 09/13/2024] [Accepted: 09/24/2024] [Indexed: 10/25/2024] Open
Abstract
BACKGROUND Hippo-avoidance prophylactic cranial irradiation (HA-PCI) requires a hippocampal avoidance zone expanded from hippocampus to ensure dose fall-off and compensate for setup errors. Most studies recommend a 5-mm margin, while it could be optimized to a 2-mm expansion. Here, we showed the details of optimized HA-PCI for limited-stage small cell lung cancer (LS-SCLC). METHODS This cohort study reviewed patients with LS-SCLC receiving optimized HA-PCI from August 2014 to June 2020 in the National Cancer Center of China. The hippo-related dose parameters were summarized. The comparison of the Hopkins Verbal Learning Test-Revised (HVLT-R) scores in different time points was conducted. The Kaplan-Meier method was used to calculate the survival rates. RESULTS A total of 112 patients were included. The average doses of hippocampus and hippocampal avoidance zone were 6.80 Gy (IQR: 6.40-7.44) and 7.63 Gy (IQR: 7.14-8.39). No differences were observed in the two radiation techniques (tomotherapy [TOMO] vs. volumetric-modulated arc therapy [VMAT]). The decline of HVLT-R score remained in a low level and not significant in assessable patients (p = 0.095). With a median follow-up of 52 months (95% CI: 47.2-56.7), the 2-year overall survival and progression-free survival were 74.1% and 50.0%, respectively. Two intracranial recurrence lesions (2.3%) located <2 mm from the hippocampus. CONCLUSIONS Optimized HA-PCI could achieve similar dose limitation by TOMO and VMAT techniques with favorable efficacy and minor toxicity.
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Affiliation(s)
- Tian-You Zhan
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Lei Deng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Wen-Qing Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Tao Zhang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Jian-Yang Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Xin Wang
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Wen-Yang Liu
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Yi-Rui Zhai
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Ze-Fen Xiao
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Qin-Fu Feng
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Nan Bi
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Ye-Xiong Li
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
| | - Zong-Mei Zhou
- Department of Radiation Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical College (PUMC), Beijing, China
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Badin F. Considerations for selecting second-line treatment in patients with progressive small cell lung cancer and the use of Lurbinectedin in this setting. Cancer Treat Res Commun 2024; 39:100803. [PMID: 38490092 DOI: 10.1016/j.ctarc.2024.100803] [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: 01/02/2024] [Revised: 02/26/2024] [Accepted: 02/27/2024] [Indexed: 03/17/2024]
Abstract
Small cell lung cancer (SCLC) is characterized by high initial responses to platinum-based chemotherapy plus immune checkpoint inhibitors; however, most patients quickly relapse and require subsequent treatment. Second-line treatment options in SCLC remain limited, and treatment algorithms are not completely consistent across the available guidelines in this setting. This review highlights key considerations regarding selection of second-line treatment for patients with relapsed SCLC. In particular, the role of lurbinectedin, which was first approved in 2020, representing the first significant addition to treatment algorithms in this setting for decades, is summarized. Future directions, including the identification of SCLC subtypes and the need for predictive biomarkers to guide patient selection and targeted therapy, are also discussed.
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Affiliation(s)
- Firas Badin
- Medical Director for Oncology Research, Baptist Health Medical Group, Lexington, KY, USA.
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Vojtíšek R. What is the current role of prophylactic cranial irradiation in the treatment algorithm for small cell lung cancer? Rep Pract Oncol Radiother 2023; 28:698-706. [PMID: 38179287 PMCID: PMC10764050 DOI: 10.5603/rpor.97432] [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: 02/22/2023] [Accepted: 09/04/2023] [Indexed: 01/06/2024] Open
Abstract
Prophylactic cranial irradiation (PCI) is considered an important technological advance made in oncology in an effort to reduce the incidence of brain metastases (BM) and improve overall survival (OS) of patients with small cell lung cancer (SCLC). Although it is often reported that PCI improves the therapeutic potential in limited-stage (LS) SCLC, no randomised trial has ever conclusively confirmed this. Nevertheless, PCI has been considered the standard of care for LS-SCLC since the late 1990s. The data supporting the use of PCI in LS-SCLC are based on an analysis of work performed prior to the current approach to staging [brain magnetic resonance imaging (MRI), positron emission tomography (PET)/computed tomography (CT)]. The evidence for the rationale and feasibility of this approach in the modern diagnostic era should be demonstrated. The situation with extensive stage (ES) SCLC is seemingly easier because, unlike LS-SCLC, we have data from two randomised trials. Unfortunately, their results are in direct conflict with each other. Although it is generally assumed that good control of brain disease leads to better quality of life, this has never been prospectively demonstrated. In fact, PCI is associated not only with increased treatment costs and some patient discomfort, but also with non-negligible potential toxicity. For this reason, efforts have been made to preserve cognitive function by sparing the hippocampus. This concept is called hippocampal avoidance. The optimal fractionation regimen is currently less controversial than the optimal integration of PCI into the treatment algorithm. A dose of 25 Gy administered in 10 fractions should remain the standard for the eventual use of PCI in patients with SCLC. In summary, PCI is not a conditio sine qua non in any indication. Neither in patients with LS-SCLC nor in patients with ES-SCLC has a clear improvement in OS been demonstrated at follow-up using current imaging modalities.
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Affiliation(s)
- Radovan Vojtíšek
- Department of Oncology and Radiotherapy, University Hospital in Pilsen, Czech Republic
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Megyesfalvi Z, Gay CM, Popper H, Pirker R, Ostoros G, Heeke S, Lang C, Hoetzenecker K, Schwendenwein A, Boettiger K, Bunn PA, Renyi-Vamos F, Schelch K, Prosch H, Byers LA, Hirsch FR, Dome B. Clinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions. CA Cancer J Clin 2023; 73:620-652. [PMID: 37329269 DOI: 10.3322/caac.21785] [Citation(s) in RCA: 153] [Impact Index Per Article: 76.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Revised: 03/30/2023] [Accepted: 04/04/2023] [Indexed: 06/19/2023] Open
Abstract
Small cell lung cancer (SCLC) is characterized by rapid growth and high metastatic capacity. It has strong epidemiologic and biologic links to tobacco carcinogens. Although the majority of SCLCs exhibit neuroendocrine features, an important subset of tumors lacks these properties. Genomic profiling of SCLC reveals genetic instability, almost universal inactivation of the tumor suppressor genes TP53 and RB1, and a high mutation burden. Because of early metastasis, only a small fraction of patients are amenable to curative-intent lung resection, and these individuals require adjuvant platinum-etoposide chemotherapy. Therefore, the vast majority of patients are currently being treated with chemoradiation with or without immunotherapy. In patients with disease confined to the chest, standard therapy includes thoracic radiotherapy and concurrent platinum-etoposide chemotherapy. Patients with metastatic (extensive-stage) disease are treated with a combination of platinum-etoposide chemotherapy plus immunotherapy with an anti-programmed death-ligand 1 monoclonal antibody. Although SCLC is initially very responsive to platinum-based chemotherapy, these responses are transient because of the development of drug resistance. In recent years, the authors have witnessed an accelerating pace of biologic insights into the disease, leading to the redefinition of the SCLC classification scheme. This emerging knowledge of SCLC molecular subtypes has the potential to define unique therapeutic vulnerabilities. Synthesizing these new discoveries with the current knowledge of SCLC biology and clinical management may lead to unprecedented advances in SCLC patient care. Here, the authors present an overview of multimodal clinical approaches in SCLC, with a special focus on illuminating how recent advancements in SCLC research could accelerate clinical development.
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Affiliation(s)
- Zsolt Megyesfalvi
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary
- National Koranyi Institute of Pulmonology, Budapest, Hungary
| | - Carl M Gay
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Helmut Popper
- Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria
| | - Robert Pirker
- Department of Medicine I, Medical University of Vienna, Vienna, Austria
| | - Gyula Ostoros
- National Koranyi Institute of Pulmonology, Budapest, Hungary
| | - Simon Heeke
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Christian Lang
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
- Division of Pulmonology, Department of Medicine II, Medical University of Vienna, Vienna, Austria
| | - Konrad Hoetzenecker
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Anna Schwendenwein
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Kristiina Boettiger
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
| | - Paul A Bunn
- University of Colorado School of Medicine, Aurora, CO, USA
| | - Ferenc Renyi-Vamos
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary
- National Koranyi Institute of Pulmonology, Budapest, Hungary
| | - Karin Schelch
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
- Center for Cancer Research, Medical University of Vienna, Vienna, Austria
| | - Helmut Prosch
- Department of Biomedical Imaging and Image-Guided Therapy, Medical University of Vienna, Vienna General Hospital, Vienna, Austria
| | - Lauren A Byers
- Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Fred R Hirsch
- Division of Medical Oncology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA
- Tisch Cancer Institute, Center for Thoracic Oncology, Mount Sinai Health System, New York, NY, USA
| | - Balazs Dome
- Department of Thoracic Surgery, Comprehensive Cancer Center, Medical University of Vienna, Vienna, Austria
- Department of Thoracic Surgery, Semmelweis University and National Institute of Oncology, Budapest, Hungary
- National Koranyi Institute of Pulmonology, Budapest, Hungary
- Department of Translational Medicine, Lund University, Lund, Sweden
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6
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Schütte W, Gütz S, Nehls W, Blum TG, Brückl W, Buttmann-Schweiger N, Büttner R, Christopoulos P, Delis S, Deppermann KM, Dickgreber N, Eberhardt W, Eggeling S, Fleckenstein J, Flentje M, Frost N, Griesinger F, Grohé C, Gröschel A, Guckenberger M, Hecker E, Hoffmann H, Huber RM, Junker K, Kauczor HU, Kollmeier J, Kraywinkel K, Krüger M, Kugler C, Möller M, Nestle U, Passlick B, Pfannschmidt J, Reck M, Reinmuth N, Rübe C, Scheubel R, Schumann C, Sebastian M, Serke M, Stoelben E, Stuschke M, Thomas M, Tufman A, Vordermark D, Waller C, Wolf J, Wolf M, Wormanns D. [Prevention, Diagnosis, Therapy, and Follow-up of Lung Cancer - Interdisciplinary Guideline of the German Respiratory Society and the German Cancer Society - Abridged Version]. Pneumologie 2023; 77:671-813. [PMID: 37884003 DOI: 10.1055/a-2029-0134] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/28/2023]
Abstract
The current S3 Lung Cancer Guidelines are edited with fundamental changes to the previous edition based on the dynamic influx of information to this field:The recommendations include de novo a mandatory case presentation for all patients with lung cancer in a multidisciplinary tumor board before initiation of treatment, furthermore CT-Screening for asymptomatic patients at risk (after federal approval), recommendations for incidental lung nodule management , molecular testing of all NSCLC independent of subtypes, EGFR-mutations in resectable early stage lung cancer in relapsed or recurrent disease, adjuvant TKI-therapy in the presence of common EGFR-mutations, adjuvant consolidation treatment with checkpoint inhibitors in resected lung cancer with PD-L1 ≥ 50%, obligatory evaluation of PD-L1-status, consolidation treatment with checkpoint inhibition after radiochemotherapy in patients with PD-L1-pos. tumor, adjuvant consolidation treatment with checkpoint inhibition in patients withPD-L1 ≥ 50% stage IIIA and treatment options in PD-L1 ≥ 50% tumors independent of PD-L1status and targeted therapy and treatment option immune chemotherapy in first line SCLC patients.Based on the current dynamic status of information in this field and the turnaround time required to implement new options, a transformation to a "living guideline" was proposed.
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Affiliation(s)
- Wolfgang Schütte
- Klinik für Innere Medizin II, Krankenhaus Martha Maria Halle-Dölau, Halle (Saale)
| | - Sylvia Gütz
- St. Elisabeth-Krankenhaus Leipzig, Abteilung für Innere Medizin I, Leipzig
| | - Wiebke Nehls
- Klinik für Palliativmedizin und Geriatrie, Helios Klinikum Emil von Behring
| | - Torsten Gerriet Blum
- Helios Klinikum Emil von Behring, Klinik für Pneumologie, Lungenklinik Heckeshorn, Berlin
| | - Wolfgang Brückl
- Klinik für Innere Medizin 3, Schwerpunkt Pneumologie, Klinikum Nürnberg Nord
| | | | - Reinhard Büttner
- Institut für Allgemeine Pathologie und Pathologische Anatomie, Uniklinik Köln, Berlin
| | | | - Sandra Delis
- Helios Klinikum Emil von Behring, Klinik für Pneumologie, Lungenklinik Heckeshorn, Berlin
| | | | - Nikolas Dickgreber
- Klinik für Pneumologie, Thoraxonkologie und Beatmungsmedizin, Klinikum Rheine
| | | | - Stephan Eggeling
- Vivantes Netzwerk für Gesundheit, Klinikum Neukölln, Klinik für Thoraxchirurgie, Berlin
| | - Jochen Fleckenstein
- Klinik für Strahlentherapie und Radioonkologie, Universitätsklinikum des Saarlandes und Medizinische Fakultät der Universität des Saarlandes, Homburg
| | - Michael Flentje
- Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Würzburg, Würzburg
| | - Nikolaj Frost
- Medizinische Klinik mit Schwerpunkt Infektiologie/Pneumologie, Charite Universitätsmedizin Berlin, Berlin
| | - Frank Griesinger
- Klinik für Hämatologie und Onkologie, Pius-Hospital Oldenburg, Oldenburg
| | | | - Andreas Gröschel
- Klinik für Pneumologie und Beatmungsmedizin, Clemenshospital, Münster
| | | | | | - Hans Hoffmann
- Klinikum Rechts der Isar, TU München, Sektion für Thoraxchirurgie, München
| | - Rudolf M Huber
- Medizinische Klinik und Poliklinik V, Thorakale Onkologie, LMU Klinikum Munchen
| | - Klaus Junker
- Klinikum Oststadt Bremen, Institut für Pathologie, Bremen
| | - Hans-Ulrich Kauczor
- Klinikum der Universität Heidelberg, Abteilung Diagnostische Radiologie, Heidelberg
| | - Jens Kollmeier
- Helios Klinikum Emil von Behring, Klinik für Pneumologie, Lungenklinik Heckeshorn, Berlin
| | | | - Marcus Krüger
- Klinik für Thoraxchirurgie, Krankenhaus Martha-Maria Halle-Dölau, Halle-Dölau
| | | | - Miriam Möller
- Krankenhaus Martha-Maria Halle-Dölau, Klinik für Innere Medizin II, Halle-Dölau
| | - Ursula Nestle
- Kliniken Maria Hilf, Klinik für Strahlentherapie, Mönchengladbach
| | | | - Joachim Pfannschmidt
- Klinik für Thoraxchirurgie, Lungenklinik Heckeshorn, Helios Klinikum Emil von Behring, Berlin
| | - Martin Reck
- Lungeclinic Grosshansdorf, Pneumologisch-onkologische Abteilung, Grosshansdorf
| | - Niels Reinmuth
- Klinik für Pneumologie, Thorakale Onkologie, Asklepios Lungenklinik Gauting, Gauting
| | - Christian Rübe
- Klinik für Strahlentherapie und Radioonkologie, Universitätsklinikum des Saarlandes, Homburg/Saar, Homburg
| | | | | | - Martin Sebastian
- Medizinische Klinik II, Universitätsklinikum Frankfurt, Frankfurt
| | - Monika Serke
- Zentrum für Pneumologie und Thoraxchirurgie, Lungenklinik Hemer, Hemer
| | | | - Martin Stuschke
- Klinik und Poliklinik für Strahlentherapie, Universitätsklinikum Essen, Essen
| | - Michael Thomas
- Thoraxklinik am Univ.-Klinikum Heidelberg, Thorakale Onkologie, Heidelberg
| | - Amanda Tufman
- Medizinische Klinik und Poliklinik V, Thorakale Onkologie, LMU Klinikum München
| | - Dirk Vordermark
- Universitätsklinik und Poliklinik für Strahlentherapie, Universitätsklinikum Halle, Halle
| | - Cornelius Waller
- Klinik für Innere Medizin I, Universitätsklinikum Freiburg, Freiburg
| | | | - Martin Wolf
- Klinikum Kassel, Klinik für Onkologie und Hämatologie, Kassel
| | - Dag Wormanns
- Evangelische Lungenklinik, Radiologisches Institut, Berlin
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Fujiwara M, Tada H. Perihippocampal Meningeal Carcinomatosis Following Hippocampal Avoidance Prophylactic Cranial Irradiation in Small Cell Lung Cancer: A Case Report. Cureus 2023; 15:e46499. [PMID: 37927701 PMCID: PMC10624598 DOI: 10.7759/cureus.46499] [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] [Accepted: 10/04/2023] [Indexed: 11/07/2023] Open
Abstract
Prophylactic cranial irradiation (PCI) for limited disease small cell lung cancer is the standard of care for curative treatment of this disease. However, neurocognitive dysfunction is one of the late adverse events of PCI and is often problematic. Recently, hippocampal avoidance prophylactic cranial irradiation (HA-PCI) is sometimes performed to prevent neurocognitive dysfunction after PCI. In HA-PCI, the question is whether or not metastases appear around the hippocampus that were not irradiated. We have experienced a case of perihippocampal meningeal carcinomatosis after HA-PCI. We also draw attention to the potential risks of performing HA-PCI based on this experience.
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Affiliation(s)
- Masateru Fujiwara
- Radiation Oncology, Osaka University Graduate School of Medicine, Suita, JPN
- Radiation Oncology, Suita Tokushukai Hospital, Suita, JPN
| | - Hirohito Tada
- Thoracic Surgery, Suita Tokushukai Hospital, Suita, JPN
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Fan X, Yang L, Qin W, Zou B, Fan B, Wang S, Wang L. Prophylactic cranial irradiation-related lymphopenia affects survival in patients with limited-stage small cell lung cancer. Heliyon 2023; 9:e16483. [PMID: 37251477 PMCID: PMC10220366 DOI: 10.1016/j.heliyon.2023.e16483] [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: 02/25/2022] [Revised: 05/15/2023] [Accepted: 05/17/2023] [Indexed: 05/31/2023] Open
Abstract
Background The study aimed to identify the relations of the absolute lymphocyte count (ALC) nadir during prophylactic cranial irradiation (PCI) and patient outcomes in limited-stage small cell lung cancer (LS-SCLC). Methods We analyzed 268 L S-SCLC patients who underwent PCI from 2012 to 2019. ALC values were collected prior, during, and 3 months post PCI. Kaplan-Meier and Cox regression analyses were performed to assess the relation of ALC to patient prognosis. Two nomograms were developed on the basis of clinical variables for survival prediction. Results Compared with the ALC before PCI (1.13 × 109 cells/L), the ALC nadir during PCI was significantly reduced by 0.68 × 109 cells/L (P < 0.001) and raised to 1.02 × 109 cells/L 3 months post PCI. Patients with a low ALC nadir during PCI (<0.68 × 109 cells/L) had inferior progression free survival (PFS) (median PFS: 17.2 m vs. 43.7 m, P = 0.019) and overall survival (OS) (median OS: 29.0 m vs 39.1 m, P = 0.012). Multivariate Cox analysis revealed that age, smoking history, clinical stage, and ALC nadir were independent OS (P = 0.006, P = 0.005, P < 0.001 and P = 0.027, respectively), as well as independent PFS predictors (P = 0.032, P = 0.012, P = 0.012 and P = 0.018, respectively). After internal cross-validation, the corrected concordance indices of the predictive nomograms for PFS and OS were 0.637 and 0.663, respectively. Conclusion LS-SCLC patients with a low ALC nadir during PCI likely have worse survival outcomes. Dynamic evaluation of the ALC during PCI is recommended for LS-SCLC patients.
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Affiliation(s)
- Xinyu Fan
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, 250000, China
| | - Linlin Yang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, 250000, China
| | - Wenru Qin
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, 250000, China
| | - Bing Zou
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, 250000, China
| | - Bingjie Fan
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, 250000, China
| | - Shijiang Wang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, 250000, China
- Cheeloo College of Medicine, Shandong University, Jinan, 250000, China
| | - Linlin Wang
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Science, Jinan, 250000, China
- Cheeloo College of Medicine, Shandong University, Jinan, 250000, China
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9
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Chu X, Zhu Z. Prophylactic cranial irradiation in small cell lung cancer: an update. Curr Opin Oncol 2023; 35:61-67. [PMID: 36421007 DOI: 10.1097/cco.0000000000000910] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
PURPOSE OF REVIEW The current review presents recent updates in the seminal literature of research on prophylactic cranial irradiation (PCI) in small cell lung cancer (SCLC). RECENT FINDINGS Brain MRI restaging before the administration of PCI reveals a substantial proportion of brain metastasis in baseline brain metastasis free extensive-stage SCLC (ES-SCLC) and limited-stage SCLC (LS-SCLC). Posthoc analyses from the CASPIAN and IMpower133 trials revealed decreases in brain metastasis rates in ES-SCLC treated with chemoimmunotherapy relative to the brain metastasis rates in ES-SCLC treated with chemotherapy alone. A recent meta-analysis of literature published after the landmark 1999 Auperin meta-analysis confirmed the survival benefit of PCI in LS-SCLC patients. A recent study employing PET before and after PCI demonstrated that hippocampal avoidance -PCI (HA-PCI) preserved the metabolic activity of the hippocampi compared with regular PCI. Two phase III trials evaluating neurocognitive functions after HA-PCI versus PCI have yielded conflicting results. Ongoing clinical trials (MAVERICK, PRIMALung, NRG CC003, NCT04535739, NCT04829708 and NCT03514849) regarding PCI versus MRI surveillance and HA-PCI versus PCI were also discussed. SUMMARY Currently, the indications for PCI in SCLC are under question in the modern MRI era. Result from prospective phase III, MRI staged and MRI monitored RCTs are expected to elucidate the role of PCI in LS-SCLC and ES-SCLC. Preliminary results indicated that adding immunotherapy to chemotherapy may reduce brain metastasis rate in SCLC. Further data to this aspect are warranted to determine the role of PCI in the immuno-chemotherapy era. The future direction for PCI should be the comprehensive integration of personalized patient selection, HA-PCI utilization and potential employment of other neurocognitive preservation strategies.
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Affiliation(s)
- Xiao Chu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center
- Department of Oncology, Shanghai Medical College, Fudan University
- Shanghai Clinical Research Center for Radiation Oncology
- Shanghai Key Laboratory of Radiation Oncology, Shanghai, China
| | - Zhengfei Zhu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center
- Department of Oncology, Shanghai Medical College, Fudan University
- Shanghai Clinical Research Center for Radiation Oncology
- Shanghai Key Laboratory of Radiation Oncology, Shanghai, China
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10
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Vucetic A, Ahmad B, Tang T. Long‑term survival in a patient with extensive‑stage small cell lung cancer treated with multiple courses of salvage stereotactic radiation after whole brain radiotherapy: A case report. Oncol Lett 2022; 24:335. [PMID: 36039058 PMCID: PMC9404686 DOI: 10.3892/ol.2022.13454] [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: 04/22/2022] [Accepted: 07/25/2022] [Indexed: 11/19/2022] Open
Abstract
Intracranial recurrence following initial cranial irradiation for extensive-stage small cell lung cancer (ES-SCLC) can often be a treatment dilemma given the aggressive nature of the disease, the overall poor prognosis and concerns regarding re-treatment toxicity. The present report describes the case of a 62-year-old man diagnosed with ES-SCLC and synchronous brain metastases who initially underwent whole brain radiotherapy, chemotherapy and consolidative thoracic radiotherapy. The patient was found to have a solitary intracranial recurrence at both 3.5 and 6 years after his diagnosis. On both occasions, the patient received salvage stereotactic radiation, 30 Gy in 5 fractions, and continues to remain functionally independent. Overall, the present case demonstrates that with the appropriate patient selection, aggressive local salvage of recurrent intracranial ES-SCLC with stereotactic radiation can yield excellent and durable clinical outcomes.
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Affiliation(s)
- Andrea Vucetic
- Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada
| | - Belal Ahmad
- Department of Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 5W9, Canada
| | - Terence Tang
- Department of Radiation Oncology, London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 5W9, Canada
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11
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Ueki K, Matsuo Y, Kishi N, Yoneyama M, Yoshida H, Sakamori Y, Ozasa H, Hirai T, Mizowaki T. Usefulness of pro-gastrin-releasing peptide as a predictor of the incidence of brain metastasis and effect of prophylactic cranial irradiation in patients with limited-stage small-cell lung cancer. JOURNAL OF RADIATION RESEARCH 2022; 63:636-645. [PMID: 35780299 PMCID: PMC9303600 DOI: 10.1093/jrr/rrac035] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 04/08/2022] [Indexed: 06/15/2023]
Abstract
Prophylactic cranial irradiation (PCI) is recommended for patients with limited-stage small-cell lung cancer (LS-SCLC) who respond well to initial treatment. However, PCI is often omitted because of its potential neurotoxicity in the era of modern diagnostic imaging devices. In the present study, we aimed to investigate the risk factors for brain metastasis (BM) in patients eligible for PCI and who may benefit more from it. Patients with LS-SCLC who responded well to definitive thoracic chemoradiotherapy were included in the present study. Competing risk regression was used to identify factors associated with BM, and the Kaplan-Meier method was used to assess overall survival (OS). Between 2004 and 2017, 62 patients were eligible for PCI and were analyzed. Of these, 38 (61.3%) underwent PCI. Overall, 17 patients (27.4%) developed BM, with a 2-year cumulative incidence of 22.8%. Multivariate analysis (MVA) revealed that pretreatment elevated pro-gastrin-releasing peptide (ProGRP) levels were associated with an increased risk for BM (HR, 7.96, P = 0.0091). PCI tended to reduce the risk of BM (HR, 0.33; P = 0.051). The use of PCI was associated with improved OS in patients with ProGRP levels > 410 pg/mL (P = 0.008), but not in those with ProGRP ≤ 410 pg/mL (P = 0.9). Pretreatment ProGRP levels may be useful in predicting the development of BM in patients with LS-SCLC who achieved a good response to initial therapy and to determine which patients should undergo PCI.
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Affiliation(s)
- Kazuhito Ueki
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
| | - Yukinori Matsuo
- Corresponding author. Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University; 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507 Japan. E-mail: ; Tel: (+81) 75-751-3762
| | - Noriko Kishi
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
| | - Masahiro Yoneyama
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
| | - Hironori Yoshida
- Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
| | - Yuichi Sakamori
- Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
| | - Hiroaki Ozasa
- Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
| | - Toyohiro Hirai
- Department of Respiratory Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
| | - Takashi Mizowaki
- Department of Radiation Oncology and Image-Applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan
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12
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Pangua C, Rogado J, Serrano-Montero G, Belda-Sanchís J, Álvarez Rodríguez B, Torrado L, Rodríguez De Dios N, Mielgo-Rubio X, Trujillo JC, Couñago F. New perspectives in the management of small cell lung cancer. World J Clin Oncol 2022; 13:429-447. [PMID: 35949427 PMCID: PMC9244973 DOI: 10.5306/wjco.v13.i6.429] [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: 04/18/2021] [Revised: 09/05/2021] [Accepted: 05/22/2022] [Indexed: 02/06/2023] Open
Abstract
The treatment of small cell lung cancer (SCLC) is a challenge for all specialists involved. New treatments have been added to the therapeutic armamentarium in recent months, but efforts must continue to improve both survival and quality of life. Advances in surgery and radiotherapy have resulted in prolonged survival times and fewer complications, while more careful patient selection has led to increased staging accuracy. Developments in the field of systemic therapy have resulted in changes to clinical guidelines and the management of patients with advanced disease, mainly with the introduction of immunotherapy. In this article, we describe recent improvements in the management of patients with SCLC, review current treatments, and discuss future lines of research.
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Affiliation(s)
- Cristina Pangua
- Department of Medical Oncology, Hospital Universitario Infanta Leonor, Madrid 28031, Spain
| | - Jacobo Rogado
- Department of Medical Oncology, Hospital Universitario Infanta Leonor, Madrid 28031, Spain
| | - Gloria Serrano-Montero
- Department of Medical Oncology, Hospital Universitario Infanta Leonor, Madrid 28031, Spain
| | - José Belda-Sanchís
- Department of Thoracic Surgery, Hospital de la Santa Creu i Sant Pau & Hospital de Mar, Universitat Autònoma de Barcelona, Barcelona 08041, Catalonia, Spain
| | - Beatriz Álvarez Rodríguez
- Department of Radiation Oncology, Hospital Universitario HM Sanchinarro, HM Hospitales, HM CIOCC Centro Integral Oncológico Clara Campal, Madrid 28050, Spain
| | - Laura Torrado
- Department of Radiation Oncology, Hospital Universitario Lucus Augusti & Instituto de Investigación Sanitaria Santiago de Compostela (IDIS), Lugo 27003, Spain
| | - Nuria Rodríguez De Dios
- Department of Radiation Oncology, Hospital Del Mar & Hospital Del Mar Medical Research Institute (IMIM) & Pompeu Fabra University, Barcelona 08003, Catalonia, Spain
| | - Xabier Mielgo-Rubio
- Department of Medical Oncology, Alcorcón Foundation University Hospital, Alcorcón 28922, Madrid, Spain
| | - Juan Carlos Trujillo
- Department of Thoracic Surgery, Hospital de la Santa Creu i Sant Pau, Barcelona 08029, Spain
| | - Felipe Couñago
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Hospital La Luz, Universidad Europea de Madrid, Madrid 28223, Spain
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13
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Zeng H, Zheng D, Witlox WJA, Levy A, Traverso A, Kong FM(S, Houben R, De Ruysscher DKM, Hendriks LEL. Risk Factors for Brain Metastases in Patients With Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. Front Oncol 2022; 12:889161. [PMID: 35756675 PMCID: PMC9226404 DOI: 10.3389/fonc.2022.889161] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 04/25/2022] [Indexed: 11/16/2022] Open
Abstract
The use of prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC) patients is controversial. Risk factors for brain metastasis (BM) development are largely lacking, hampering personalized treatment strategies. This study aimed to identify the possible risk factors for BM in SCLC.We systematically searched the Pubmed database (1 January 1995 to 18 January 2021) according to the PRISMA guidelines. Eligibility criteria: studies reporting detailed BM data with an adequate sample size (randomized clinical trials [RCTs]: N ≥50; non-RCTs: N ≥100) in patients with SCLC. We summarized the reported risk factors and performed meta-analysis to estimate the pooled hazard ratios (HR) if enough qualified data (i.e., two or more studies; the same study type; the same analysis method; and HRs retrievable) were available. In total, 61/536 records were eligible (18 RCTs and 39 non-RCTs comprising 13,188 patients), in which 57 factors were reported. Ten factors qualified BM data for meta-analysis: Limited stage disease (LD) (HR = 0.34, 95% CI: 0.17-0.67; P = 0.002) and older age (≥65) (HR = 0.70, 95% CI: 0.54-0.92; P = 0.01) were associated with less BM; A higher T stage (≥T3) (HR = 1.72, 95% CI: 1.16-2.56; P = 0.007) was a significant risk factor for BM. Male sex (HR = 1.24, 95% CI: 0.99-1.54; P = 0.06) tended to be a risk factor, and better PS (0-1) (HR = 0.66, 95% CI: 0.42-1.02; P = 0.06) tended to have less BM. Smoking, thoracic radiotherapy dose were not significant (P >0.05). PCI significantly decreased BM (P <0.001), but did not improve OS in ED-SCLC (P = 0.81). A higher PCI dose did not improve OS (P = 0.11). The impact on BM was conflicting between Cox regression data (HR = 0.59, 95% CI: 0.26-1.31; P = 0.20) and competing risk regression data (HR = 0.74, 95% CI: 0.55-0.99; P = 0.04). Compared to M0-M1a, M1b was a risk factor for OS (P = 0.01) in ED-SCLC, but not for BM (P = 0.19). As regular brain imaging is rarely performed, high-quality data is lacking. Other factors such as N-stage and blood biomarkers had no qualified data to perform meta-analysis. In conclusion, younger age, higher T stage, and ED are risk factors for BM, suggesting that PCI should be especially discussed in such cases. Individual patient data (IPD) meta-analysis and well-designed RCTs are needed to better identify more risk factors and further confirm our findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021228391, identifier CRD42021228391.
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Affiliation(s)
- Haiyan Zeng
- Department of Radiation Oncology (Maastro), GROW School for Oncology, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Danyang Zheng
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Willem J. A. Witlox
- Department of Clinical Epidemiology and Medical Technology Assessment, GROW—School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Antonin Levy
- Department of Radiation Oncology, Gustave Roussy, Villejuif, France
- Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France
| | - Alberto Traverso
- Department of Radiation Oncology (Maastro), GROW School for Oncology, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Feng-Ming (Spring) Kong
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Ruud Houben
- Department of Radiation Oncology (Maastro), GROW School for Oncology, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Dirk K. M. De Ruysscher
- Department of Radiation Oncology (Maastro), GROW School for Oncology, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Lizza E. L. Hendriks
- Department of Pulmonary Diseases, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, Netherlands
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14
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Radiation therapy for extensive-stage small-cell lung cancer in the era of immunotherapy. Cancer Lett 2022; 541:215719. [PMID: 35597478 DOI: 10.1016/j.canlet.2022.215719] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2022] [Revised: 04/30/2022] [Accepted: 05/03/2022] [Indexed: 12/23/2022]
Abstract
Unlike non-small-cell lung cancer (NSCLC), the progression of small-cell lung cancer (SCLC) is slow. Extensive-stage SCLC (ES-SCLC) is a serious threat to human health, with a 5-year survival rate of <7%. Chemotherapy has been the first-line treatment for the past 30 years. The anti-PD-L1 checkpoint blockades durvalumab and atezolizumab have greatly prolonged overall survival and have become the standard first-line therapy for ES-SCLC since the CASPIAN and IMpower133 trials. In the era of chemotherapy, radiation therapy (RT), including thoracic radiation therapy (TRT) and brain radiation therapy (BRT), has shown clinical effects in randomized and retrospective studies on ES-SCLC. RT-immunotherapy has shown exciting synergistic effects in NSCLC. For ES-SCLC, the clinical effects of combining TRT/BRT with immunotherapy have not yet been systematically explored. In this review, we found that studies on RT-immunotherapy in ES-SCLC are relatively few and limited to early phase studies focusing on toxicity. The efficacy and safety profiles of early phase studies encourage prospective clinical trials. In this review, we discuss the best population, optimum TRT dose, proper TRT time, and strategies for reducing radiation-induced neurotoxicity. Furthermore, we suggest that biomarkers and patient performance status should be fully assessed before RT-immunotherapy treatment. Prospective trials are needed to provide more evidence for RT-immunotherapy applications in ES-SCLC.
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15
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Xue S, Zeng H, Yan S, Wang Q, Jia X. Prophylactic Cranial Irradiation for Extensive-Stage Small-Cell Lung Cancer: A Controversial Area. Front Oncol 2022; 12:772282. [PMID: 35198438 PMCID: PMC8858935 DOI: 10.3389/fonc.2022.772282] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 01/17/2022] [Indexed: 11/13/2022] Open
Abstract
Small-cell lung cancer (SCLC) is a highly aggressive malignant tumor that is prone to lead to the development of brain metastases (BM). The application of prophylactic cranial irradiation (PCI) has been regarded as an important technological advance made in cancer therapy to reduce the occurrence of BM and improve patient survival. The benefits of PCI in the treatment of limited-stage SCLC have been confirmed. However, there has been continuous controversy about the indications and advantages of PCI for extensive-stage SCLC (ES-SCLC) because of the conflicting results from two prospective trials. In this review, we aimed to discuss the relevant controversy and progress made in the clinical application of PCI in ES-SCLC.
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16
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Rodríguez de Dios N, Couñago F, Murcia-Mejía M, Rico-Oses M, Calvo-Crespo P, Samper P, Vallejo C, Luna J, Trueba I, Sotoca A, Cigarral C, Farré N, Manero RM, Durán X, Gispert JD, Sánchez-Benavides G, Rognoni T, Torrente M, Capellades J, Jiménez M, Cabada T, Blanco M, Alonso A, Martínez-San Millán J, Escribano J, González B, López-Guerra JL. Randomized Phase III Trial of Prophylactic Cranial Irradiation With or Without Hippocampal Avoidance for Small-Cell Lung Cancer (PREMER): A GICOR-GOECP-SEOR Study. J Clin Oncol 2021; 39:3118-3127. [PMID: 34379442 DOI: 10.1200/jco.21.00639] [Citation(s) in RCA: 86] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 05/17/2021] [Accepted: 07/01/2021] [Indexed: 11/20/2022] Open
Abstract
PURPOSE Radiation dose received by the neural stem cells of the hippocampus during whole-brain radiotherapy has been associated with neurocognitive decline. The key concern using hippocampal avoidance-prophylactic cranial irradiation (HA-PCI) in patients with small-cell lung cancer (SCLC) is the incidence of brain metastasis within the hippocampal avoidance zone. METHODS This phase III trial enrolled 150 patients with SCLC (71.3% with limited disease) to standard prophylactic cranial irradiation (PCI; 25 Gy in 10 fractions) or HA-PCI. The primary objective was the delayed free recall (DFR) on the Free and Cued Selective Reminding Test (FCSRT) at 3 months; a decrease of 3 points or greater from baseline was considered a decline. Secondary end points included other FCSRT scores, quality of life (QoL), evaluation of the incidence and location of brain metastases, and overall survival (OS). Data were recorded at baseline, and 3, 6, 12, and 24 months after PCI. RESULTS Participants' baseline characteristics were well balanced between the two groups. The median follow-up time for living patients was 40.4 months. Decline on DFR from baseline to 3 months was lower in the HA-PCI arm (5.8%) compared with the PCI arm (23.5%; odds ratio, 5; 95% CI, 1.57 to 15.86; P = .003). Analysis of all FCSRT scores showed a decline on the total recall (TR; 8.7% v 20.6%) at 3 months; DFR (11.1% v 33.3%), TR (20.3% v 38.9%), and total free recall (14.8% v 31.5%) at 6 months, and TR (14.2% v 47.6%) at 24 months. The incidence of brain metastases, OS, and QoL were not significantly different. CONCLUSION Sparing the hippocampus during PCI better preserves cognitive function in patients with SCLC. No differences were observed with regard to brain failure, OS, and QoL compared with standard PCI.
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Affiliation(s)
- Núria Rodríguez de Dios
- Radiation Oncology, Hospital del Mar, Barcelona, Spain
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
- Pompeu Fabra University, Barcelona, Spain
| | - Felipe Couñago
- Department of Radiation Oncology, Hospital Universitario Quirónsalud, Madrid, Spain
| | - Mauricio Murcia-Mejía
- Department of Radiation Oncology, Hospital Universitario Sant Joan de Reus, Reus, Tarragona, Spain
| | - Mikel Rico-Oses
- Department of Radiation Oncology, Complejo Hospitalario Navarra, Pamplona, Spain
| | - Patricia Calvo-Crespo
- Department of Radiation Oncology, Hospital Universitario de Santiago de Compostela, Santiago de Compostela, A Coruña, Spain
| | - Pilar Samper
- Department of Radiation Oncology, Hospital Universitario Rey Juan Carlos, Móstoles, Madrid, Spain
| | - Carmen Vallejo
- Department of Radiation Oncology, Hospital Universitario Ramón y Cajal, Madrid, Spain
| | - Javier Luna
- Department of Radiation Oncology, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain
| | - Itziar Trueba
- Department of Radiation Oncology, Hospital Universitario de Álava-sede Txagorritxu.Vitoria-Gasteiz, Spain
| | - Amalia Sotoca
- Department of Radiation Oncology, Hospital Ruber Internacional, Madrid, Spain
| | - Cristina Cigarral
- Department of Radiation Oncology, Hospital Clínico de Salamanca, Salamanca, Spain
| | - Núria Farré
- Department of Radiation Oncology, Hospital Universitario Santa Creu i Sant Pau, Barcelona, Spain
| | - Rosa M Manero
- Department of Neurology, Hospital del Mar, Barcelona, Spain
| | - Xavier Durán
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
| | - Juan Domigo Gispert
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
- Pompeu Fabra University, Barcelona, Spain
- BarcelonaBeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Madrid, Spain
| | - Gonzalo Sánchez-Benavides
- IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain
- BarcelonaBeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain
- Centro de Investigación Biomédica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Madrid, Spain
| | - Teresa Rognoni
- Department of Neurology, Clínica Universidad de Navarrra, Madrid, Spain
| | - Margarita Torrente
- Department of Psychology, School of Educational Sciences and Psychology, Rovira i Virgili University, Tarragona, Spain
- Laboratory of Toxicology and Environmental Health, School of Medicine, IISPV, Rovira i Virgili University, Tarragona, Spain
| | | | - Mar Jiménez
- Department of Radiology, Hospital Universitario Quirónsalud, Madrid, Spain
| | - Teresa Cabada
- Department of Radiology, Complejo Hospitalario Navarra, Pamplona, Spain
| | - Miguel Blanco
- Department of Radiology, Hospital Universitario de Santiago de Compostela, Santiago de Compostela, A Coruña, Spain
| | - Ana Alonso
- Department of Radiology, Hospital Universitario Rey Juan Carlos, Móstoles, Madrid, Spain
| | | | - José Escribano
- Department of Radiology, Hospital Ruber Internacional, Madrid, Spain
| | - Beatriz González
- Department of Radiation Oncology, Hospital Clínico de Salamanca, Salamanca, Spain
| | - José Luis López-Guerra
- Department of Radiation Oncology, Hospital Universitario Virgen del Rocío, Sevilla, Spain
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17
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Abraham AG, Roa W. Hippocampal avoidance in prophylactic cranial irradiation for small cell lung cancer: benefits and pitfalls. J Thorac Dis 2021; 13:3235-3245. [PMID: 34164216 PMCID: PMC8182537 DOI: 10.21037/jtd-2019-rbmlc-01] [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: 04/13/2020] [Accepted: 09/03/2020] [Indexed: 11/25/2022]
Abstract
Small cell lung cancers (SCLC) are a group of cancers that are clinically and pathologically different from other lung cancers. They are associated with high recurrence rates and mortality, and many patients present with metastatic disease. Approximately ten percent of SCLC patients have brain metastases at time of diagnosis, and the cumulative incidence of brain metastases increases to more than fifty percent at two years, even with optimal treatment. Hence, in patients without brain metastases at presentation, prophylactic cranial irradiation (PCI) is an important component of treatment along with systemic chemotherapy and radiotherapy. The goal of PCI is to decrease the incidence of subsequent symptomatic brain metastases in patients who show an initial response to the systemic treatment. Various clinical trials have evaluated the utility of PCI and found substantial benefit. Unfortunately, the long-term toxicity associated with PCI, namely the neuro-cognitive impairment that may develop in patients as a result of the radiation toxicity to the hippocampal areas of the brain, has raised concern both for patients and their treating physicians. Various techniques have been tried to ameliorate the neuro-cognitive impairment associated with PCI, including pharmacological agents and highly conformal hippocampal avoidance radiation. All of these have shown promise, but there is a lack of clarity about the optimal way forward. Hippocampal avoidance PCI appears to be an excellent option and a number of groups are currently evaluating this technique. Although there is clear benefit with this specialized radiation treatment, there are also concerns about the risk of disease recurrence in the undertreated hippocampal areas. This review attempts to compile the available data regarding the benefits and pitfalls associated with hippocampal avoidance PCI in the setting of SCLC.
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Affiliation(s)
| | - Wilson Roa
- Department of Radiation Oncology, Cross Cancer Institute, Edmonton, Canada
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18
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Couñago F, de la Pinta C, Gonzalo S, Fernández C, Almendros P, Calvo P, Taboada B, Gómez-Caamaño A, Guerra JLL, Chust M, González Ferreira JA, Álvarez González A, Casas F. GOECP/SEOR radiotherapy guidelines for small-cell lung cancer. World J Clin Oncol 2021; 12:115-143. [PMID: 33767969 PMCID: PMC7968106 DOI: 10.5306/wjco.v12.i3.115] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Revised: 01/25/2021] [Accepted: 02/12/2021] [Indexed: 02/06/2023] Open
Abstract
Small cell lung cancer (SCLC) accounts for approximately 20% of all lung cancers. The main treatment is chemotherapy (Ch). However, the addition of radiotherapy significantly improves overall survival (OS) in patients with non-metastatic SCLC and in those with metastatic SCLC who respond to Ch. Prophylactic cranial irradiation reduces the risk of brain metastases and improves OS in both metastatic and non-metastatic patients. The 5-year OS rate in patients with limited-stage disease (non-metastatic) is slightly higher than 30%, but less than 5% in patients with extensive-stage disease (metastatic). The present clinical guidelines were developed by Spanish radiation oncologists on behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Society of Radiation Oncology to provide a current review of the diagnosis, planning, and treatment of SCLC. These guidelines emphasise treatment fields, radiation techniques, fractionation, concomitant treatment, and the optimal timing of Ch and radiotherapy. Finally, we discuss the main indications for reirradiation in local recurrence.
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Affiliation(s)
- Felipe Couñago
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Hospital La Luz, Universidad Europea de Madrid, Madrid 28223, Madrid, Spain
| | - Carolina de la Pinta
- Department of Radiation Oncology, Hospital Universitario Ramón y Cajal, Madrid 28034, Spain
| | - Susana Gonzalo
- Department of Radiation Oncology, Hospital Universitario La Princesa, Madrid 28006, Spain
| | - Castalia Fernández
- Department of Radiation Oncology, GenesisCare Madrid, Madrid 28043, Spain
| | - Piedad Almendros
- Department of Radiation Oncology, Hospital General Universitario, Valencia 46014, Spain
| | - Patricia Calvo
- Department of Radiation Oncology, Hospital Clínico Universitario Santiago de Compostela, Santiago de Compostela 15706, Spain
| | - Begoña Taboada
- Department of Radiation Oncology, Hospital Clínico Universitario Santiago de Compostela, Santiago de Compostela 15706, Spain
| | - Antonio Gómez-Caamaño
- Department of Radiation Oncology, Hospital Clínico Universitario Santiago de Compostela, Santiago de Compostela 15706, Spain
| | - José Luis López Guerra
- Department of Radiation Oncology, Hospital Universitario Virgen del Rocío, Sevilla 41013, Spain
| | - Marisa Chust
- Department of Radiation Oncology, Fundación Instituto Valenciano de Oncología, Valencia 46009, Spain
| | | | | | - Francesc Casas
- Department of Radiation Oncology, Thoracic Unit, Hospital Clinic, Barcelona 08036, Spain
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19
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Kang Y, Jin Y, Li Q, Yuan X. Advances in Lung Cancer Driver Genes Associated With Brain Metastasis. Front Oncol 2021; 10:606300. [PMID: 33537237 PMCID: PMC7848146 DOI: 10.3389/fonc.2020.606300] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2020] [Accepted: 12/01/2020] [Indexed: 12/24/2022] Open
Abstract
Brain metastasis, one of the common complications of lung cancer, is an important cause of death in patients with advanced cancer, despite progress in treatment strategies. Lung cancers with positive driver genes have higher incidence and risk of brain metastases, suggesting that driver events associated with these genes might be biomarkers to detect and prevent disease progression. Common lung cancer driver genes mainly encode receptor tyrosine kinases (RTKs), which are important internal signal molecules that interact with external signals. RTKs and their downstream signal pathways are crucial for tumor cell survival, invasion, and colonization in the brain. In addition, new tumor driver genes, which also encode important molecules closely related to the RTK signaling pathway, have been found to be closely related to the brain metastases of lung cancer. In this article, we reviewed the relationship between lung cancer driver genes and brain metastasis, and summarized the mechanism of driver gene-associated pathways in brain metastasis. By understanding the molecular characteristics during brain metastasis, we can better stratify lung cancer patients and alert those at high risk of brain metastasis, which helps to promote individual therapy for lung cancer.
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Affiliation(s)
- Yalin Kang
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Yu Jin
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qianxia Li
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xianglin Yuan
- Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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20
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Is There a Role for Hypofractionated Thoracic Radiation Therapy in Limited-Stage Small Cell Lung Cancer? A Propensity Score Matched Analysis. Int J Radiat Oncol Biol Phys 2020; 108:575-586. [PMID: 32544575 PMCID: PMC7293491 DOI: 10.1016/j.ijrobp.2020.06.008] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2020] [Revised: 06/07/2020] [Accepted: 06/08/2020] [Indexed: 01/09/2023]
Abstract
Purpose Various radiation schedules are used in concurrent chemoradiation therapy for limited-stage small cell lung cancer (LS-SCLC). Since there is currently no randomized evidence comparing hypofractionated radiation therapy (HFRT) and conventionally fractionated radiation therapy (CFRT), the aim of this study was to compare overall survival (OS), progression-free survival (PFS), and toxicity of HFRT and CFRT in LS-SCLC. Methods and Materials Patients with LS-SCLC treated between 2000 and 2013 with HFRT (40 Gy/15 fractions, 45 Gy/15 fractions, 45 Gy/20 fractions) or CFRT (60 Gy/30 or 66 Gy/33 fractions) were included. Propensity scores were generated using a multivariable logistic regression model. Patients were matched on a 1:1 ratio with a caliper distance of 0.20. OS and PFS were estimated by the Kaplan-Meier method and compared using log-rank tests. As a sensitivity analysis, univariable and multivariable Cox regression was performed including all patients without matching. Logistic regression was performed to identify predictors of pulmonary and esophageal adverse events. Results In the overall group of 117 patients, there were significant baseline differences between the HFRT and CFRT cohorts. Patients who received CFRT were older, more often smoked concurrently with treatment, had higher Eastern Cooperative Oncology Group performance status, different T and N stage patterns, and more commonly received concurrent chemoradiation therapy and prophylactic cranial irradiation. After propensity score matching for these differences, 72 patients were included, 36 in the HFRT and CFRT cohorts, respectively. There was no difference in OS (P = .724), PFS (P = .862), or any pulmonary (P = .350) or esophageal (P = .097) adverse events between cohorts. Skin adverse events were significantly higher for CFRT (41.7%) compared with HFRT (16.7%, P = .020). Multivariable Cox regression also revealed no differences in OS (P = .886) or PFS (P = .717) between all HFRT and CFRT patients, without matching. No grade 5 adverse events were observed. Conclusions In LS-SCLC patients, HFRT was associated with comparable survival and toxicity outcomes and may be considered as an alternative to CFRT, should its efficacy be confirmed in prospective studies.
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21
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Simone CB, Bogart JA, Cabrera AR, Daly ME, DeNunzio NJ, Detterbeck F, Faivre-Finn C, Gatschet N, Gore E, Jabbour SK, Kruser TJ, Schneider BJ, Slotman B, Turrisi A, Wu AJ, Zeng J, Rosenzweig KE. Radiation Therapy for Small Cell Lung Cancer: An ASTRO Clinical Practice Guideline. Pract Radiat Oncol 2020; 10:158-173. [PMID: 32222430 PMCID: PMC10915746 DOI: 10.1016/j.prro.2020.02.009] [Citation(s) in RCA: 122] [Impact Index Per Article: 24.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Accepted: 02/15/2020] [Indexed: 12/14/2022]
Abstract
PURPOSE Several sentinel phase III randomized trials have recently been published challenging traditional radiation therapy (RT) practices for small cell lung cancer (SCLC). This American Society for Radiation Oncology guideline reviews the evidence for thoracic RT and prophylactic cranial irradiation (PCI) for both limited-stage (LS) and extensive-stage (ES) SCLC. METHODS The American Society for Radiation Oncology convened a task force to address 4 key questions focused on indications, dose fractionation, techniques and timing of thoracic RT for LS-SCLC, the role of stereotactic body radiation therapy (SBRT) compared with conventional RT in stage I or II node negative SCLC, PCI for LS-SCLC and ES-SCLC, and thoracic consolidation for ES-SCLC. Recommendations were based on a systematic literature review and created using a consensus-building methodology and system for grading evidence quality and recommendation strength. RESULTS The task force strongly recommends definitive thoracic RT administered once or twice daily early in the course of treatment for LS-SCLC. Adjuvant RT is conditionally recommended in surgically resected patients with positive margins or nodal metastases. Involved field RT delivered using conformal advanced treatment modalities to postchemotherapy volumes is also strongly recommended. For patients with stage I or II node negative disease, SBRT or conventional fractionation is strongly recommended, and chemotherapy should be delivered before or after SBRT. In LS-SCLC, PCI is strongly recommended for stage II or III patients who responded to chemoradiation, conditionally not recommended for stage I patients, and should be a shared decision for patients at higher risk of neurocognitive toxicities. In ES-SCLC, radiation oncologist consultation for consideration of PCI versus magnetic resonance surveillance is strongly recommended. Lastly, the use of thoracic RT is strongly recommended in select patients with ES-SCLC after chemotherapy treatment, including a conditional recommendation in those responding to chemotherapy and immunotherapy. CONCLUSIONS RT plays a vital role in both LS-SCLC and ES-SCLC. These guidelines inform best clinical practices for local therapy in SCLC.
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Affiliation(s)
| | - Jeffrey A Bogart
- Department of Radiation Oncology, SUNY Upstate Medical University, Syracuse, NY
| | - Alvin R Cabrera
- Department of Radiation Oncology, Kaiser Permanente, Seattle, WA
| | - Megan E Daly
- Department of Radiation Oncology, University of California Davis, Sacramento, CA
| | - Nicholas J DeNunzio
- Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA
| | - Frank Detterbeck
- Department of Thoracic Surgery, Yale University School of Medicine, New Haven, CT
| | - Corinne Faivre-Finn
- Division of Cancer Science, University of Manchester and The Christie NHS Foundation Trust, Manchester, United Kingdom
| | | | - Elizabeth Gore
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI
| | - Salma K Jabbour
- Department of Radiation Oncology, Rutgers University, New Brunswick, NJ
| | - Tim J Kruser
- Department of Radiation Oncology, Northwestern Memorial Hospital, Chicago, IL
| | - Bryan J Schneider
- Department of Medical Oncology, University of Michigan, Ann Arbor, MI
| | - Ben Slotman
- Department of Radiation Oncology, VU University Medical Center, Amsterdam, Netherlands
| | - Andrew Turrisi
- Department of Radiation Oncology, James H. Quillen VA Medical Center, Mountain Home, TN
| | - Abraham J Wu
- Department of Radiation Oncology, Memorial Sloan Kettering, New York, NY
| | - Jing Zeng
- Department of Radiation Oncology, University of Washington, Seattle, WA
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22
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Edelman MJ. Prophylactic Cranial Irradiation for Small-Cell Lung Cancer: Time for a Reassessment. Am Soc Clin Oncol Educ Book 2020; 40:24-28. [PMID: 32421453 DOI: 10.1200/edbk_281041] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Prophylactic cranial irradiation (PCI) has been an accepted part of the management of both limited and small-cell lung cancer; however, the data that support its use in limited-stage disease is based on an analysis of trials done before currently accepted approaches to staging (i.e., brain MRI and/or PET scanning) were available. For extensive disease, data are available from two randomized studies that are in direct conflict. This article explores the basic rationale for PCI and the evidence indicating that it is time to readdress the question of its routine use.
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23
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Farrell MJ, Yahya JB, Degnin C, Chen Y, Holland JM, Henderson MA, Jaboin JJ, Harkenrider MM, Thomas CR, Mitin T. Elective Nodal Irradiation for Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Practice Patterns. Clin Lung Cancer 2020; 21:443-449.e4. [PMID: 32245625 DOI: 10.1016/j.cllc.2020.02.020] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2019] [Revised: 12/18/2019] [Accepted: 02/26/2020] [Indexed: 10/24/2022]
Abstract
BACKGROUND Traditionally, elective nodal irradiation (ENI) has been used in clinical trials that have established thoracic radiotherapy as instrumental in improving survival for patients with limited-stage small-cell lung cancer (LS-SCLC). However, several reports have suggested that the omission of ENI might be appropriate. Current US practice patterns are unknown regarding ENI for patients with LS-SCLC. MATERIALS AND METHODS We surveyed US radiation oncologists via an institutional review board-approved questionnaire. The questions covered demographics, treatment recommendations, and self-assessed knowledge of key clinical trials. χ2 and Cochran-Armitage tests were used to evaluate for statistically significant correlations between responses. RESULTS We received 309 responses. Of the respondents, 21% recommended ENI for N0 LS-SCLC, 29% for N1, and 30% for N2; 64% did not recommend ENI for any of these clinical scenarios. The respondents who recommended ENI were more likely to have been practicing for > 10 years (P < .001), more likely to be in private practice (P = .04), and less likely to be familiar with the ongoing Cancer and Leukemia Group B 30610 trial (P = .04). Almost all respondents (93%) prescribed the same radiation dose to the primary disease and involved lymph nodes. When delivering ENI, 36% prescribed the same dose to the involved and elective nodes, and 64% prescribed a lower dose to the elective nodes. CONCLUSION Nearly two thirds of respondents did not recommend ENI, which represents a shift in practice. A recent large clinical trial that omitted ENI reported greater overall survival than previously reported and lower-than-expected radiation toxicities, lending further evidence that omitting ENI should be considered a standard treatment strategy.
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Affiliation(s)
- Matthew J Farrell
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Jehan B Yahya
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Catherine Degnin
- Knight Cancer Institute, Biostatistics Shared Resources, Oregon Health & Science University, Portland, OR
| | - Yiyi Chen
- Knight Cancer Institute, Biostatistics Shared Resources, Oregon Health & Science University, Portland, OR
| | - John M Holland
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | | | - Jerry J Jaboin
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Matthew M Harkenrider
- Department of Radiation Oncology, Stritch School of Medicine, Loyola University Chicago, Chicago, IL
| | - Charles R Thomas
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Timur Mitin
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR.
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24
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Nakazaki K, Yomo S, Kondoh T, Serizawa T, Kenai H, Kawagishi J, Sato S, Nagano O, Aiyama H, Kawai H, Hasegawa T, Iwai Y, Nagatomo Y, Kida Y, Nishigaki M. Salvage gamma knife radiosurgery for active brain metastases from small-cell lung cancer after whole-brain radiation therapy: a retrospective multi-institutional study (JLGK1701). J Neurooncol 2020; 147:67-76. [PMID: 31933257 DOI: 10.1007/s11060-020-03397-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2019] [Accepted: 01/08/2020] [Indexed: 11/25/2022]
Abstract
PURPOSE To evaluate the efficacy of gamma knife radiosurgery (GKS) for brain metastases (BMs) from small-cell lung cancer after whole-brain radiotherapy (WBRT). METHODS We retrospectively analyzed the usefulness and safety of GKS in 163 patients from 15 institutions with 1-10 active BMs after WBRT. The usefulness and safety of GKS were evaluated using statistical methods. RESULTS The median age was 66 years, and 79.1% of patients were men. The median number and largest diameter of BM were 2.0 and 1.4 cm, respectively. WBRT was administered prophylactically in 46.6% of patients. The median overall survival (OS) was 9.3 months, and the neurologic mortality was 20.0%. Crude incidences of local control failure and new lesion appearance were 36.6% and 64.9%, respectively. A BM diameter ≥ 1.0 cm was a significant risk factor for local progression (hazard ratio [HR] 2.556, P = 0.039) and neurologic death (HR 4.940, P = 0.031). Leukoencephalopathy at the final follow-up was more prevalent in the therapeutic WBRT group than in the prophylactic group (P = 0.019). The symptom improvement rate was 61.3%, and neurological function was preserved for a median of 7.6 months. Therapeutic WBRT was not a significant risk factor for OS, neurological death, local control, or functional deterioration (P = 0.273, 0.490, 0.779, and 0.560, respectively). Symptomatic radiation-related adverse effects occurred in 7.4% of patients. CONCLUSIONS GKS can safely preserve neurological function and prevent neurologic death in patients with 1-10 small, active BMs after prophylactic and therapeutic WBRT.
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Affiliation(s)
- Kiyoshi Nakazaki
- Department of Neurosurgery, Brain Attack Center Ota Memorial Hospital, 3-6-28 Okinogami, Fukuyama, Hiroshima, 7200825, Japan.
| | - Shoji Yomo
- Department of Neurosurgery, Aizawa Hospital, Matsumoto, Nagano, Japan
| | - Takeshi Kondoh
- Department of Neurosurgery, Shinsuma General Hospital, Kobe, Hyogo, Japan
| | - Toru Serizawa
- Tokyo Gamma Unit Center, Tsukiji Neurological Clinic, Tokyo, Japan
| | - Hiroyuki Kenai
- Department of Neurosurgery, Nagatomi Neurosurgical Hospital, Oita, Japan
| | - Jun Kawagishi
- Jiro Suzuki Memorial GammaHouse, Furukawa Seiryo Hospital, Osaki, Miyagi, Japan
| | - Sonomi Sato
- Department of Neurosurgery, Southern Tohoku Research Institute for Neuroscience, Southern Tohoku General Hospital, Koriyama, Fukushima, Japan
| | - Osamu Nagano
- Gamma Knife House, Chiba Cerebral and Cardiovascular Center, Ichihara, Chiba, Japan
| | - Hitoshi Aiyama
- Katsuta Hospital Mito GammaHouse, Hitachi-naka, Ibaraki, Japan
| | - Hideya Kawai
- Department of Neurosurgery, Research Institute for Brain and Blood-Vessels-Akita, Akita, Japan
| | | | - Yoshiyasu Iwai
- Department of Neurosurgery, Osaka City General Hospital, Osaka, Japan
| | - Yasushi Nagatomo
- Department of Neurosurgery, Kouseikai Takai Hospital, Tenri, Nara, Japan
| | - Yoshihisa Kida
- Department of Neurosurgery, Ookuma Hospital, Nagoya, Japan
| | - Masakazu Nishigaki
- Department of Human Health Sciences, School of Medicine, Kyoto University, Kyoto, Japan
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25
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Chu X, Li S, Xia B, Chu L, Yang X, Ni J, Zou L, Li Y, Xie C, Lin J, Zhu Z. Patterns of brain metastasis immediately before prophylactic cranial irradiation (PCI): implications for PCI optimization in limited-stage small cell lung cancer. Radiat Oncol 2019; 14:171. [PMID: 31533763 PMCID: PMC6749639 DOI: 10.1186/s13014-019-1371-4] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 08/28/2019] [Indexed: 12/12/2022] Open
Abstract
Background Prophylactic cranial irradiation (PCI) is indicated for limited-stage small cell lung cancer (LS-SCLC) with good response to chemoradiotherapy (CRT). However, brain metastasis (BM) developed in LS-SCLC before PCI is not rare. In this study, we comprehensively investigated the features of pre-PCI BMs, aiming to explore the potential of PCI optimization for LS-SCLC. Methods One-hundred-ten LS-SCLC patients achieving clinical complete remission after definitive CRT with contrast-enhanced cranial magnetic resonance imaging (MRI) at baseline and immediately before PCI were included. The time trend and risk factors for pre-PCI BM were evaluated. Several radiological features, including numbers, sizes, and locations of pre-PCI BMs, were investigated to explore the technical feasibility of stereotactic radiotherapy and hippocampal-avoidance (HA) PCI. Results Twenty-four (21.8%) of the LS-SCLC patients harbored pre-PCI BM, all except one were asymptomatic. CRT duration (CRT-D) was the only independent risk factor for pre-PCI BM. The pre-PCI BM rate gradually increased in line with a growing time interval between treatment initiation and pre-PCI MRI. Pre-PCI BM and prolonged CRT-D were both correlated with worse overall survival. Of 129 pre-PCI intracranial lesions, 2 (1.5%) were in the HA region. Eight of the 24 (33.3%) pre-PCI BM patients were ineligible for stereotactic radiotherapy. Conclusion Our findings suggest that PCI is still of importance in LS-SCLC, and MRI evaluation before PCI is indispensable. Investigations are warranted to explore the possibility of moving PCI up to before CRT completion in LS-SCLC patients with prolonged CRT-D. HA-PCI could be considered to reduce neurotoxicity. Electronic supplementary material The online version of this article (10.1186/s13014-019-1371-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Xiao Chu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Shuyan Li
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Bingqing Xia
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.,Department of Radiology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China
| | - Li Chu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Xi Yang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Jianjiao Ni
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Liqing Zou
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Yida Li
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Congying Xie
- Radiotherapy and Chemotherapy Department, the 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China
| | - Jie Lin
- Department of Medical Oncology, the Second Affiliated Hospital of Kunming Medical University, 374 Dianmian Avenue, Wuhua District, Kunming, 650101, Yunnan, China.
| | - Zhengfei Zhu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
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26
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Sayan M, Satir Turk M, Celik A, Cuneyt Kurul I, Irfan Tastepe A. Surgical outcomes of early-stage small-cell lung cancer: single-center experience. Asian Cardiovasc Thorac Ann 2019; 27:187-191. [PMID: 30661378 DOI: 10.1177/0218492319826724] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
Abstract
BACKGROUND Small-cell lung cancer is a highly aggressive and metastatic epithelial lung malignancy. A small percentage of these tumors can be detected at an early stage and may be appropriate for surgical treatment. We analyzed the data of patients with early-stage small-cell lung cancer who underwent lobectomy and mediastinal lymph node dissection. METHODS Between January 2011 and December 2016, 26 patients with early-stage small-cell lung cancer underwent lobectomy and mediastinal lymph node dissection and were included the study. The mean age was 60.9 years and 18 (69.2%) were male. Patients with increased uptake of 18 F-fludeoxyglucose in mediastinal or distant organs on positron-emission tomography computed tomography, or lung resections other than lobectomy, were not included in the study. RESULTS The most common tumor location was the right upper lobe. The diagnoses were achieved by intraoperative frozen section study in almost all patients (92.3%). Mean overall survival was 58.5 ± 6.7 months (range 45-71 months) and the 5-year survival rate was 53%. We found that a statistically significant correlation between lymph node metastasis in N1 or N2 stations and survival. There was also a significant relationship between N2 nodal metastasis and recurrence. CONCLUSION As stated in the current guidelines, lung lobectomy and mediastinal lymph node resection should be considered in early-stage small-cell lung cancers. Survival outcomes of surgery for early-stage small-cell lung cancer are similar to the results in non-small-cell lung cancer.
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Affiliation(s)
- Muhammet Sayan
- Department of Thoracic Surgery, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Merve Satir Turk
- Department of Thoracic Surgery, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Ali Celik
- Department of Thoracic Surgery, Gazi University Faculty of Medicine, Ankara, Turkey
| | - Ismail Cuneyt Kurul
- Department of Thoracic Surgery, Gazi University Faculty of Medicine, Ankara, Turkey
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27
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Kou P, Wang H, Yang D, Zhang Y, Yu J. Application of prophylactic cranial irradiation in limited-stage small-cell lung cancer: which patients could benefit? Future Oncol 2019; 15:3237-3245. [PMID: 30091368 DOI: 10.2217/fon-2018-0481] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/29/2023] Open
Abstract
Aim: To analyze the role of prophylactic cranial irradiation (PCI) on the survival for patients with limited-stage small-cell lung cancer (LS-SCLC). Patients & methods: We screened patients from SEER database. Kaplan–Meier analysis and Cox proportional hazard model were used to evaluate factors influencing survival. Results: LS-SCLC patients who receiving PCI were associated with better overall survival (OS; p < 0.001) and cancer-specific survival (CSS; p < 0.001). Multivariable Cox analysis revealed PCI was an independent prognostic factor for OS (p < 0.001) and CSS (p < 0.001). In subgroup analysis, there were no OS and CSS differences between PCI and no PCI groups in black patients and patient with a tumor size <5 cm (all p > 0.05). Conclusion: PCI remains an effective method for most LS-SCLC patients. However, caution should be taken in recommending PCI for black patients and patients with a tumor size <5 cm. Further clinical trials are necessary to validate our results and identify the most suitable patients for PCI in the modern era.
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Affiliation(s)
- Peisi Kou
- Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China
| | - Haiyong Wang
- Department of Internal Medicine-Oncology, Shandong Cancer Hospital & Institute, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, PR China
| | - Daoke Yang
- Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China
| | - Yan Zhang
- Department of Radiation Oncology, Shandong Cancer Hospital & Institute, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, PR China
| | - Jinming Yu
- Department of Radiation Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, PR China
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Morgan TN, Turner RM, Baptiste J, Lyon TD, Maranchie JK, Hrebinko RL, Davies BJ, Gingrich JR, Jacobs BL. Small cell bladder cancer: should we consider prophylactic cranial irradiation? Int Braz J Urol 2018; 45:299-305. [PMID: 30521161 PMCID: PMC6541124 DOI: 10.1590/s1677-5538.ibju.2018.0242] [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: 04/09/2018] [Accepted: 09/29/2018] [Indexed: 11/22/2022] Open
Abstract
Purpose: To describe the clinical characteristics, treatment patterns, and outcomes in patients with small cell bladder cancer at our institution, including those who received prophylactic cranial irradiation (PCI) for the prevention of intracranial recurrence. Materials and Methods: Patients with small cell bladder cancer treated at a single institution between January 1990 and August 2015 were identified and analyzed retrospectively for demographics, tumor stage, treatment, and overall survival. Results: Of 44 patients diagnosed with small cell bladder cancer, 11 (25%) had metastatic disease at the time of presentation. Treatment included systemic chemotherapy (70%), radical surgery (59%), and local radiation (39%). Six patients (14%) received PCI. Median overall survival was 10 months (IQR 4 – 41). Patients with extensive disease had worse overall survival than those with organ confined disease (8 months vs. 36 months, respectively, p = 0.04). Among those who received PCI, 33% achieved 5 - year survival. Conclusion: Outcomes for patients with small cell bladder cancer remain poor. Further research is indicated to determine if PCI increases overall survival in small call bladder cancer patients, especially those with extensive disease who respond to chemotherapy.
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Affiliation(s)
| | - Robert M Turner
- Department of Urology, University of Pittsburgh, Pennsylvania, U.S.A
| | - Julian Baptiste
- School of Medicine, University of Pittsburgh, Pennsylvania, U.S.A
| | - Timothy D Lyon
- Department of Urology, University of Pittsburgh, Pennsylvania, U.S.A
| | - Jodi K Maranchie
- Department of Urology, University of Pittsburgh, Pennsylvania, U.S.A
| | - Ronald L Hrebinko
- Department of Urology, University of Pittsburgh, Pennsylvania, U.S.A
| | - Benjamin J Davies
- Department of Urology, University of Pittsburgh, Pennsylvania, U.S.A
| | | | - Bruce L Jacobs
- Department of Urology, University of Pittsburgh, Pennsylvania, U.S.A
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Chen MY, Hu X, Xu YJ, Chen M. The impact of prophylactic cranial irradiation for post-operative patients with limited stage small cell lung cancer. Medicine (Baltimore) 2018; 97:e13029. [PMID: 30383664 PMCID: PMC6221751 DOI: 10.1097/md.0000000000013029] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2018] [Accepted: 10/05/2018] [Indexed: 11/26/2022] Open
Abstract
To evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients who received definitive surgery for surgically resected small cell lung cancer (SCLC).A retrospective analysis was performed on post-operative SCLC patients treated in Zhejiang Cancer Hospital from January 2003 to December 2015. According to the treatment modality, patients were allocated to PCI group and non-PCI group. Univariate survival analysis was performed by the Kaplan-Meier method. Multivariate survival analysis was performed by a Cox proportional hazards model.A total of 52 patients were included for analysis, among which, 19 patients were in PCI group and 33 were in non-PCI group. Multivariate analysis revealed that PCI (HR = .330; P = .041) was an independently favorable prognostic factor for the overall survival. The median overall survival (OS) time was 32.9 months in PCI group, and 20.4 months in non-PCI group. The 2-year OS rates were 78.0% and 38.0% in PCI and non-PCI group respectively (P = .023). The brain metastasis-free survival (BMFS) rate at 2-year in PCI group was significantly higher than those of non-PCI group (89.0% vs 53.0%, respectively, P = .026).In conclusion, PCI might be suggested for limited SCLC patients who received definitive surgery.
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Affiliation(s)
- Meng-yuan Chen
- Department of Radiation Oncology, Zhejiang Key Lab of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou
- Zhejiang Chinese Medicinal University, Hangzhou, Zhejiang Province, China
| | - Xiao Hu
- Department of Radiation Oncology, Zhejiang Key Lab of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou
| | - Yu-jin Xu
- Department of Radiation Oncology, Zhejiang Key Lab of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou
| | - Ming Chen
- Department of Radiation Oncology, Zhejiang Key Lab of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou
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Farrell MJ, Yahya JB, Degnin C, Chen Y, Holland JM, Henderson MA, Jaboin JJ, Harkenrider MM, Thomas CR, Mitin T. Radiation Dose and Fractionation for Limited-stage Small-cell Lung Cancer: Survey of US Radiation Oncologists on Practice Patterns. Clin Lung Cancer 2018; 20:13-19. [PMID: 30219240 DOI: 10.1016/j.cllc.2018.08.015] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2018] [Revised: 07/24/2018] [Accepted: 08/11/2018] [Indexed: 12/23/2022]
Abstract
BACKGROUND Thoracic radiotherapy (TRT) with concurrent chemotherapy is standard for limited-stage small-cell lung cancer (LS-SCLC). However, the optimal dosing and fractionation remain unclear. The National Comprehensive Cancer Network guidelines have recommended either 45 Gy delivered twice daily (BID) or 60 to 70 Gy delivered once daily (QD). However, the current practice patterns among US radiation oncologists are unknown. MATERIALS AND METHODS We surveyed US radiation oncologists using an institutional review board-approved questionnaire. The questions covered demographic data, self-rated knowledge of key trials, and treatment recommendations. RESULTS We received 309 responses from radiation oncologists. Of the 309 radiation oncologists, 60% preferred TRT QD and 76% acknowledged QD to be more common in their practice. The respondents in academic settings were more likely to endorse BID treatment by both preference (P = .001) and actual practice (P = .009). The concordance between preferring QD and administering QD in practice was 100%. In contrast, 40% of respondents who preferred BID actually administered QD more often. Also, 15% of physicians would be unwilling to switch from QD to BID and 3% would be unwilling to switch from BID to QD, even on patient request. Most respondents (88%) recommended a dose of 45 Gy for BID treatment. For QD treatment, the division was greater, with 54% recommending 60 Gy, 30% recommending 63 to 66 Gy, and 10% recommending 70 Gy. CONCLUSION Substantial variation exists in how US radiation oncologists approach TRT dosing and fractionation for LS-SCLC. Three quarters of our respondents reported administering TRT QD most often. The most common doses were 60 Gy QD and 45 Gy BID. The results of the present survey have provided the most up-to-date information on US practice patterns for LS-SCLC.
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Affiliation(s)
- Matthew J Farrell
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Jehan B Yahya
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Catherine Degnin
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Yiyi Chen
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - John M Holland
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Mark A Henderson
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Jerry J Jaboin
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Matthew M Harkenrider
- Department of Radiation Oncology, Stritch School of Medicine, Loyola University Chicago, Chicago, IL
| | - Charles R Thomas
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Timur Mitin
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR.
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Abstract
Brain metastases (BM) are the most commonly diagnosed type of central nervous system tumor in the United States. Estimates of the frequency of BM vary significantly, as there is no nationwide reporting system for metastases. BM may be the first sign of a previously undiagnosed cancer, or occur years or decades after the primary cancer was diagnosed. Incidence of BM varies significantly by primary cancer site. Lung, breast, and melanoma continue to be the leading cause of BM. These tumors are increasingly more common as new therapeutics, advanced imaging, and improved screening have led to lengthened survival after primary diagnosis for cancer patients. BM are difficult to treat, and for most individuals the diagnosis of BM generally portends a poor prognosis.
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Affiliation(s)
- Quinn T Ostrom
- Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, United States
| | - Christina Huang Wright
- Brain Tumor and Neuro-oncology Center, Department of Neurosurgery, University Hospitals Case Medical Center, Case Western Reserve School of Medicine, Cleveland, OH, United States
| | - Jill S Barnholtz-Sloan
- Case Comprehensive Cancer Center, Case Western Reserve University School of Medicine, Cleveland, OH, United States.
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Sio TT, Prayongrat A, Zhang Y, Lin Q, Xu T, Liao Z, Yue J. The Road Less Traveled: Should We Omit Prophylactic Cranial Irradiation for Patients With Small Cell Lung Cancer? Clin Lung Cancer 2018; 19:289-293. [PMID: 29665993 DOI: 10.1016/j.cllc.2018.03.006] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2017] [Revised: 02/07/2018] [Accepted: 03/10/2018] [Indexed: 01/29/2023]
Abstract
New randomized data from Japan have raised questions regarding the use of prophylactic cranial irradiation for patients with extensive-stage small-cell lung cancer but without detectable brain metastases on magnetic resonance imaging. In the present focused review, we examine the general role of prophylactic cranial irradiation in the management of small-cell lung cancer and present relevant controversies from both sides of the discussion. Future directions for clinical investigation and research are also highlighted. Strategies for neurocognitive protection, including memantine use and hippocampal sparing using modulated radiotherapy techniques, are also presented.
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Affiliation(s)
- Terence T Sio
- Department of Radiation Oncology, Mayo Clinic Arizona, Phoenix, AZ
| | - Anussara Prayongrat
- Department of Radiation Oncology, King Chulalongkorn Memorial Hospital, Chulalongkorn University Bangkok, Bangkok, Thailand
| | - Yun Zhang
- School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Cancer Hospital affiliated to Shandong University, Jinan, Shandong, China
| | - Qin Lin
- Department of Radiation Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, China
| | - Ting Xu
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Zhongxing Liao
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jinbo Yue
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Cancer Hospital affiliated to Shandong University, Jinan, Shandong, China.
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Prophylactic Cranial Irradiation for Resectable Small-Cell Lung Cancer. Clin Lung Cancer 2018; 19:115-119. [DOI: 10.1016/j.cllc.2017.08.004] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2017] [Revised: 08/08/2017] [Accepted: 08/18/2017] [Indexed: 11/20/2022]
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Prayongrat A, Tao R, Allen PK, Guha N, Rao G, Zhao Z, Li J, Brown PD, McGovern SL. Outcomes of stereotactic radiosurgery of brain metastases from neuroendocrine tumors. Neurooncol Pract 2018; 5:37-45. [PMID: 31385968 DOI: 10.1093/nop/npx009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022] Open
Abstract
Background Stereotactic radiosurgery (SRS) is an established treatment for brain metastases, yet little is known about SRS for neuroendocrine tumors given their unique natural history. Objective To determine outcomes and toxicity from SRS in patients with brain metastases arising from neuroendocrine tumors. Methods Thirty-three patients with brain metastases from neuroendocrine tumors who underwent SRS were retrospectively reviewed. Median age was 61 years and median Karnofsky performance status was 80. Primary sites were lung (87.9%), cervix (6.1%), esophagus (3%), and prostate (3%). Ten patients (30.3%) received upfront SRS, 7 of whom had neuroendocrine tumors other than small cell lung carcinoma. Kaplan-Meier survival and Cox regression analyses were performed to determine prognostic factors for survival. Results With median follow-up after SRS of 5.3 months, local and distant brain recurrence developed in 5 patients (16.7%) and 20 patients (66.7%), respectively. Median overall survival (OS) after SRS was 6.9 months. Patients with progressive disease per Response Assessment in Neuro-Oncology-Brain Metastases (RANO-BM) criteria at 4 to 6 weeks after SRS had shorter median time to developing recurrence at a distant site in the brain and shorter OS than patients without progressive disease: 1.4 months and 3.3 months vs 11.4 months and 12 months, respectively (both P < .001). Toxicity was more likely in lesions of small cell histology than in lesions of other neuroendocrine tumor histology, 15.7% vs 3.3% (P = .021). No cases of grade 3 to 5 necrosis occurred. Conclusions SRS is an effective treatment option for patients with brain metastases from neuroendocrine tumors with excellent local control despite slightly higher toxicity rates than expected. Progressive disease at 4 to 6 weeks after SRS portends a poor prognosis.
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Affiliation(s)
- Anussara Prayongrat
- Division of Radiation Oncology, Department of Radiology, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
| | - Randa Tao
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Pamela K Allen
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Nandita Guha
- Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Ganesh Rao
- Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Zhongxiang Zhao
- Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Jing Li
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Paul D Brown
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
| | - Susan L McGovern
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
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Farrell MJ, Yahya JB, Degnin C, Chen Y, Holland JM, Henderson MA, Jaboin JJ, Harkenrider MM, Thomas CR, Mitin T. Prophylactic Cranial Irradiation for Limited-Stage Small-Cell Lung Cancer: Survey of US Radiation Oncologists on Current Practice Patterns. Clin Lung Cancer 2018; 19:371-376. [PMID: 29559208 DOI: 10.1016/j.cllc.2018.02.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2018] [Revised: 02/12/2018] [Accepted: 02/18/2018] [Indexed: 11/30/2022]
Abstract
PURPOSE Prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (LS-SCLC) is considered the standard of care. Meta-analysis of 7 clinical trials indicates a survival benefit to PCI, but all of these trials were conducted in the pre-magnetic resonance imaging (MRI) era. Therefore, routine brain imaging with MRI before PCI-as recommended by National Comprehensive Cancer Network guidelines-is not directly supported by the evidence. Current US practice patterns for patients with LS-SCLC are unknown. MATERIALS AND METHODS We surveyed practicing US radiation oncologists via an institutional review board-approved online questionnaire. Questions covered demographic information and treatment recommendations for LS-SCLC. RESULTS We received 309 responses from US radiation oncologists. Ninety-eight percent recommended PCI for patients with LS-SCLC, 96% obtained brain MRI before PCI, 33% obtained serial brain imaging with MRI after PCI to detect new metastases, and 35% recommended memantine for patients undergoing PCI. Recommending memantine was associated with fewer years of practice (P < .001), fewer lung cancer patients treated per year (P = .045), and fewer LS-SCLC patients treated per year (P = .024). CONCLUSION Almost all responding radiation oncologists recommended PCI and pre-PCI brain MRI for LS-SCLC patients with disease responsive to initial therapy. Only a third of respondents followed these patients with serial brain MRI. Approximately one third provided memantine therapy to try to limit neurocognitive effects of PCI. Further research is warranted to determine the best treatment for patients with LS-SCLC. This survey can inform the development of future trials that depend on participation from radiation oncologists.
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Affiliation(s)
- Matthew J Farrell
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR.
| | - Jehan B Yahya
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Catherine Degnin
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Yiyi Chen
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - John M Holland
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Mark A Henderson
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Jerry J Jaboin
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Matthew M Harkenrider
- Department of Radiation Oncology, Stritch School of Medicine, Loyola University Chicago, Chicago, IL
| | - Charles R Thomas
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
| | - Timur Mitin
- Department of Radiation Medicine, Oregon Health & Science University, Portland, OR
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Almodovar K, Iams WT, Meador CB, Zhao Z, York S, Horn L, Yan Y, Hernandez J, Chen H, Shyr Y, Lim LP, Raymond CK, Lovly CM. Longitudinal Cell-Free DNA Analysis in Patients with Small Cell Lung Cancer Reveals Dynamic Insights into Treatment Efficacy and Disease Relapse. J Thorac Oncol 2018; 13:112-123. [PMID: 28951314 PMCID: PMC5827950 DOI: 10.1016/j.jtho.2017.09.1951] [Citation(s) in RCA: 109] [Impact Index Per Article: 15.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2017] [Revised: 08/16/2017] [Accepted: 09/08/2017] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Patients with SCLC have a poor prognosis and limited treatment options. Because access to longitudinal tumor samples is very limited in patients with this disease, we chose to focus our studies on the characterization of plasma cell-free DNA (cfDNA) for rapid, noninvasive monitoring of disease burden. METHODS We developed a liquid biopsy assay that quantifies somatic variants in cfDNA. The assay detects single nucleotide variants, copy number alterations, and insertions or deletions in 14 genes that are frequently mutated in SCLC, including tumor protein p53 gene (TP53), retinoblastoma 1 gene (RB1), BRAF, KIT proto-oncogene receptor tyrosine kinase gene (KIT), notch 1 gene (NOTCH1), notch 2 gene (NOTCH2), notch 3 gene (NOTCH3), notch 4 gene (NOTCH4), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha gene (PIK3CA), phosphatase and tensin homolog gene (PTEN), fibroblast growth factor receptor 1 gene (FGFR1), v-myc avian myelocytomatosis viral oncogene homolog gene (MYC), v-myc avian myelocytomatosis viral oncogene lung carcinoma derived homolog gene (MYCL1), and v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog gene (MYCN). RESULTS Over the course of 26 months of peripheral blood collection, we examined 140 plasma samples from 27 patients. We detected disease-associated mutations in 85% of patient samples with mutant allele frequencies ranging from 0.1% to 87%. In our cohort, 59% of the patients had extensive-stage disease, and the most common mutations occurred in TP53 (70%) and RB1 (52%). In addition to mutations in TP53 and RB1, we detected alterations in 10 additional genes in our patient population (PTEN, NOTCH1, NOTCH2, NOTCH3, NOTCH4, MYC, MYCL1, PIK3CA, KIT, and BRAF). The observed allele frequencies and copy number alterations tracked closely with treatment responses. Notably, in several cases analysis of cfDNA provided evidence of disease relapse before conventional imaging. CONCLUSIONS These results suggest that liquid biopsies are readily applicable in patients with SCLC and can potentially provide improved monitoring of disease burden, depth of response to treatment, and timely warning of disease relapse in patients with this disease.
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Affiliation(s)
- Karinna Almodovar
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Wade T. Iams
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | - Catherine B. Meador
- Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN
| | - Zhiguo Zhao
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN
| | - Sally York
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN,Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN
| | - Leora Horn
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN,Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN
| | - Yingjun Yan
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
| | | | - Heidi Chen
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN
| | - Yu Shyr
- Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN
| | | | | | - Christine M. Lovly
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN,Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN,Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN,Corresponding author: Christine M. Lovly, MD, PhD, Vanderbilt-Ingram Cancer Center, 2220 Pierce Avenue, 777 Preston Research Building, Nashville, TN 37232-6307, Phone 615-936-3457,
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Kesarwala AH, Lu DJ, Xanthopoulos E, Apisarnthanarax S, Cengel KA, Evans TL, Aggarwal C, Cohen RB, Langer CJ, Rengan R, Simone CB. The Role of Advanced Imaging in Assessing Response to Definitive Chemoradiation Before Prophylactic Cranial Irradiation in Limited-Stage Small-Cell Lung Cancer. Clin Lung Cancer 2017; 19:e205-e209. [PMID: 29153967 DOI: 10.1016/j.cllc.2017.10.001] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2017] [Revised: 07/26/2017] [Accepted: 10/04/2017] [Indexed: 12/17/2022]
Abstract
INTRODUCTION Prophylactic cranial irradiation (PCI) improves survival for small-cell lung cancer (SCLC). Evidence for PCI in limited-stage SCLC largely derives from studies requiring only chest x-ray (CXR) to determine remission status. We analyzed thoracic chemoradiation therapy (TCRT) outcomes according to imaging modality to determine which patients benefitted most from PCI. PATIENTS AND METHODS All limited-stage SCLC patients who received TCRT as well as PCI at our institution were reviewed. Imaging between TCRT end and PCI start was characterized as complete (CR), partial (PR), or other response. RESULTS Thirty-eight consecutive patients were assessed for TCRT response before PCI with CXR (n = 21), chest computed tomography (CT; n = 27), and/or positron emission tomography (PET)/CT (n = 11). CR was identified on 71% of CXRs, 41% of CT scans, and 18% of PET/CT scans. Median survival was 28.3 months for the entire cohort and did not differ for patients who had CXR alone versus CT and/or PET/CT for restaging (P = .78) or those with PR using any modality versus CR using all modalities (22.6 months vs. 45.5 months; P = .22). CT CR patients had numerical but not statistically significant improved 2-year (P = .18) and 3-year (P = .13) survival compared with CT PR. CONCLUSION CXR remains an appropriate modality to assess TCRT response before PCI in limited-stage SCLC. Advanced imaging did not inform the decision to offer PCI in this study. Because of similar excellent survival profiles independent of imaging modality and TCRT response, this analysis suggests limited-stage SCLC patients with PR using any modality should not be denied PCI, akin to standards for extensive-stage SCLC.
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Affiliation(s)
- Aparna H Kesarwala
- Radiation Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD.
| | - Diana J Lu
- Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Eric Xanthopoulos
- Department of Radiation Oncology, Columbia University Medical Center, New York, NY
| | - Smith Apisarnthanarax
- Department of Radiation Oncology, University of Washington Medical Center, Seattle, WA
| | - Keith A Cengel
- Department of Radiation Oncology, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Tracey L Evans
- Division of Hematology/Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Charu Aggarwal
- Division of Hematology/Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Roger B Cohen
- Division of Hematology/Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Corey J Langer
- Division of Hematology/Oncology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA
| | - Ramesh Rengan
- Department of Radiation Oncology, University of Washington Medical Center, Seattle, WA
| | - Charles B Simone
- Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD
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Bloom BC, Augustyn A, Sepesi B, Patel S, Shah SJ, Komaki RU, Schild SE, Chun SG. Prophylactic Cranial Irradiation Following Surgical Resection of Early-Stage Small-Cell Lung Cancer: A Review of the Literature. Front Oncol 2017; 7:228. [PMID: 29034208 PMCID: PMC5626817 DOI: 10.3389/fonc.2017.00228] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 09/07/2017] [Indexed: 12/19/2022] Open
Abstract
With increasing use of low-dose screening CT scans, the diagnosis of early-stage small-cell lung cancer (SCLC) without evidence of mediastinal nodal or distant metastasis is likely to become more common, but the role of adjuvant therapies such as prophylactic cranial irradiation (PCI) are not well understood in this population. We performed a review of the literature pertaining to the impact of PCI in patients who underwent surgical resection of early-stage SCLC. Four studies were identified that were pertinent including three single-institution retrospective analyses and a National Cancer Database analysis. Based upon these studies, we estimate the rate of brain metastases to be 10-15% for Stage I and 15-25% for Stage II disease without PCI. However, the impact of PCI on the development of brain metastases and its ultimate impact on overall survival were not consistent across these studies. In summary, there is sparse evidence to guide recommendations for PCI following resection of early-stage SCLC. While it may be reasonable to offer PCI to maximize likelihood of cure, alternative strategies such as observation with close imaging follow-up can also be considered for the appropriate patient given the known neurocognitive side effects of PCI.
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Affiliation(s)
| | - Alexander Augustyn
- Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Boris Sepesi
- Department of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Sunil Patel
- Department of General Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Shalin J Shah
- Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Ritsuko U Komaki
- Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Steven E Schild
- Department of Radiation Oncology, Mayo Clinic Scottsdale, Scottsdale, AZ, United States
| | - Stephen G Chun
- Division of Radiation Oncology, Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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Choi M, Lee Y, Moon SH, Han JY, Kim HT, Lee JS. Effect of Accurate Staging Using Positron Emission Tomography on the Outcomes of Prophylactic Cranial Irradiation in Patients With Limited Stage Small-Cell Lung Cancer. Clin Lung Cancer 2017; 18:77-84. [DOI: 10.1016/j.cllc.2016.06.012] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2016] [Revised: 06/16/2016] [Accepted: 06/21/2016] [Indexed: 11/26/2022]
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Subramaniam DS, Warner EA, Giaccone G. Ganetespib for small cell lung cancer. Expert Opin Investig Drugs 2016; 26:103-108. [DOI: 10.1080/13543784.2017.1268599] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
| | - Eiran A. Warner
- Division of Hematology-Oncology, Georgetown University, Washington, DC, USA
| | - Giuseppe Giaccone
- Division of Hematology-Oncology, Georgetown University, Washington, DC, USA
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Bernhardt D, Bozorgmehr F, Adeberg S, Opfermann N, von Eiff D, Rieber J, Kappes J, Foerster R, König L, Thomas M, Debus J, Steins M, Rieken S. Outcome in patients with small cell lung cancer re-irradiated for brain metastases after prior prophylactic cranial irradiation. Lung Cancer 2016; 101:76-81. [DOI: 10.1016/j.lungcan.2016.09.010] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2016] [Revised: 09/09/2016] [Accepted: 09/13/2016] [Indexed: 11/29/2022]
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Prophylactic Cranial Irradiation for Patients with Surgically Resected Small Cell Lung Cancer. J Thorac Oncol 2016; 12:347-353. [PMID: 27725211 DOI: 10.1016/j.jtho.2016.09.133] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2016] [Revised: 08/06/2016] [Accepted: 09/25/2016] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Data on prophylactic cranial irradiation (PCI) after complete resection of SCLC are limited. The purpose of this study was to investigate the impact of PCI in this population. METHODS We retrospectively identified completely resected SCLC at the Shanghai Chest Hospital between January 2006 and January 2014. RESULTS A total of 349 patients (115 patients who received PCI [the PCI-treated cohort] and 234 patients who did not [the non-PCI-treated cohort]) were included in the study. The results demonstrated that the PCI-treated cohort had longer overall survival than the non-PCI-treated cohort among patients with pathologic stage (p-stage) II (hazard ratio [HR] = 0.54, 95% confidence interval [CI]: 0.30-0.99, p = 0.047) and p-stage III (HR = 0.54, 95% CI: 0.34-0.86, p = 0.009) disease. Among patients with p-stage III disease, there was a significantly higher risk for cerebral recurrence from the time of diagnosis in the non-PCI-treated cohort (p = 0.018). With regard to patients with p-stage I disease, neither overall survival benefit (HR = 1.61, 95% CI: 0.68-3.83, p = 0.282) nor risk for cerebral recurrence (p = 0.389) was significant between the PCI-treated and non-PCI-treated cohorts. CONCLUSIONS The data presented in the current study support using PCI in patients with p-stage II/III disease but not in patients with p-stage I disease. A relatively lower risk for brain metastases in p-stage I patients might explain the inferior efficacy of PCI in this population.
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Saji H, Marushima H, Nakamura H. Role of adjuvant therapy in early-stage small-cell lung cancer: comment on a population-based cohort study of patients with early-stage small-cell lung cancer. J Thorac Dis 2016; 8:E1404-E1407. [PMID: 27867641 DOI: 10.21037/jtd.2016.10.58] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Affiliation(s)
- Hisashi Saji
- Department of Chest Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, Japan
| | - Hideki Marushima
- Department of Chest Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, Japan
| | - Haruhiko Nakamura
- Department of Chest Surgery, St. Marianna University School of Medicine, 2-16-1 Sugao, Miyamae-ku, Kawasaki, Kanagawa, Japan
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Chen Y, Li J, Hu Y, Zhang Y, Lin Z, Zhao Z, Jiao S. Prophylactic cranial irradiation could improve overall survival in patients with extensive small cell lung cancer. Strahlenther Onkol 2016; 192:905-912. [DOI: 10.1007/s00066-016-1038-0] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Accepted: 08/11/2016] [Indexed: 11/24/2022]
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Sakaguchi M, Maebayashi T, Aizawa T, Ishibashi N, Saito T. Treatment outcomes of patients with small cell lung cancer without prophylactic cranial irradiation. J Thorac Dis 2016; 8:2571-2579. [PMID: 27747011 DOI: 10.21037/jtd.2016.08.73] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
BACKGROUND Prophylactic cranial irradiation (PCI) is indicated for limited disease (LD) in small cell lung cancer (SCLC) patients who achieve a complete or near-complete response; however, it is sometimes not administered because of possible adverse reactions or patient refusal. Here we assessed treatment outcomes among patients with SCLC who were not treated with PCI. METHODS The medical records of 60 patients (45 men, 15 women; mean age, 68 years; age range, 51-82 years) with SCLC were retrospectively reviewed. The tumors were staged by TNM classification. Two, 2, 5, 4, 32, and 15 patients had stage IA, IB, IIA, IIB, IIIA, and IIIB tumors, respectively. The patients were treated with thoracic radiotherapy (TRT) and four courses of chemotherapy. RESULTS Our subjects had a median survival of 25 months and 2- and 5-year survival rates of 52.6% and 25.3%, respectively. Univariate analysis revealed that the development of brain metastasis, performance status (PS), and T-stage were significant factors correlated with survival rate. Multivariate analysis identified only PS [hazard ratio (HR), 5.845, 95% confidence interval (CI), 2.333-14.63, P=0.002] and brain metastasis as independent prognostic variables (HR, 2.344, 95% CI, 1.071-5.128, P=0.033). CONCLUSIONS The results of our study demonstrated that the outcomes of treatment without PCI were improved, as compared with those of previously published data. Our findings may be used as reference data when PCI cannot be performed.
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Affiliation(s)
- Masakuni Sakaguchi
- Department of Radiology, Nihon University School of Medicine, Tokyo, Japan
| | - Toshiya Maebayashi
- Department of Radiology, Nihon University School of Medicine, Tokyo, Japan
| | - Takuya Aizawa
- Department of Radiology, Nihon University School of Medicine, Tokyo, Japan
| | - Naoya Ishibashi
- Department of Radiology, Nihon University School of Medicine, Tokyo, Japan
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Ozawa Y, Omae M, Fujii M, Matsui T, Kato M, Sagisaka S, Asada K, Karayama M, Shirai T, Yasuda K, Nakamura Y, Inui N, Yamada K, Yokomura K, Suda T. Management of brain metastasis with magnetic resonance imaging and stereotactic irradiation attenuated benefits of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer. BMC Cancer 2015; 15:589. [PMID: 26275617 PMCID: PMC4537586 DOI: 10.1186/s12885-015-1593-2] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2014] [Accepted: 08/05/2015] [Indexed: 12/12/2022] Open
Abstract
Background Magnetic resonance imaging (MRI) enables a more sensitive detection of brain metastasis and stereotactic irradiation (SRI) efficiently controls brain metastasis. In limited-stage small cell lung cancer (LS-SCLC), prophylactic cranial irradiation (PCI) in patients with good responses to initial treatment is recommended based on the survival benefit shown in previous clinical trials. However, none of these trials evaluated PCI effects using the management of brain metastasis with MRI or SRI. This study aimed to determine the effects of MRI and SRI on the benefits of PCI in patients with LS-SCLC. Methods The clinical records of pathologically proven SCLC from January 2006 to June 2013 in facilities equipped with or had access to SRI in Japan were retrospectively reviewed. Patients with LS-SCLC and complete or good partial responses after initial treatment were included in the study and analyzed by the Kaplan-Meier method. Results Of 418 patients with SCLC, 124 met criteria and were divided into patients receiving PCI (PCI group; n = 29) and those without PCI (non-PCI groups; n = 95). At baseline, ratios of patients with stage III were significantly advantageous for the non-PCI group, although younger age and high ratios of complete response and MRI confirmed absence of brain metastasis were advantageous for the PCI group. Neither median survival times (25 vs. 34 months; p = 0.256) nor cumulative incidence of brain metastasis during 2 years (45.5 vs. 30.8 %; p = 0.313) significantly differed between the two groups. Moreover, these factors did not significantly differ among patients with stage III disease (25 vs. 26 months; p = 0.680, 42.3 vs. 52.3 %; p = 0.458, respectively). Conclusion PCI may be less beneficial in patients with LS-SCLC if the management with MRI and SRI is available.
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Affiliation(s)
- Yuichi Ozawa
- Department of Respiratory Medicine, Respiratory Disease Center, 3453 Mikatahara, Kita-ku, Hamamatsu, Shizuoka, 433-8558, Japan.
| | - Minako Omae
- Department of Respiratory Medicine, Respiratory Disease Center, 3453 Mikatahara, Kita-ku, Hamamatsu, Shizuoka, 433-8558, Japan
| | - Masato Fujii
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1 Kita-Ando, Aoi-ku, Shizuoka, Shizuoka, 420-8527, Japan
| | - Takashi Matsui
- Department of Respiratory Medicine, Respiratory Disease Center, 3453 Mikatahara, Kita-ku, Hamamatsu, Shizuoka, 433-8558, Japan
| | - Masato Kato
- Department of Respiratory Medicine, Respiratory Disease Center, 3453 Mikatahara, Kita-ku, Hamamatsu, Shizuoka, 433-8558, Japan
| | - Shinya Sagisaka
- Department of Respiratory Medicine, Iwata City Hospital, 512-3 Okubo, Iwata, Shizuoka, 438-0002, Japan
| | - Kazuhiro Asada
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1 Kita-Ando, Aoi-ku, Shizuoka, Shizuoka, 420-8527, Japan
| | - Masato Karayama
- Department of Clinical Oncology, 1-20-1 Handayama, Higashi Ward, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Toshihiro Shirai
- Department of Respiratory Medicine, Shizuoka General Hospital, 4-27-1 Kita-Ando, Aoi-ku, Shizuoka, Shizuoka, 420-8527, Japan
| | - Kazumasa Yasuda
- Department of Respiratory Medicine, Iwata City Hospital, 512-3 Okubo, Iwata, Shizuoka, 438-0002, Japan
| | - Yutaro Nakamura
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Naoki Inui
- Department of Clinical Pharmacology and Therapeutics, 1-20-1 Handayama, Higashi Ward, Hamamatsu, Shizuoka, 431-3192, Japan
| | - Kazunari Yamada
- Department of Radiation Oncology, Seirei Mikatahara General Hospital, 3453 Mikatahara, Kita-ku, Hamamatsu, Shizuoka, 433-8558, Japan
| | - Koshi Yokomura
- Department of Respiratory Medicine, Respiratory Disease Center, 3453 Mikatahara, Kita-ku, Hamamatsu, Shizuoka, 433-8558, Japan
| | - Takafumi Suda
- Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi Ward, Hamamatsu, Shizuoka, 431-3192, Japan
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Kundapur V, Ellchuk T, Ahmed S, Gondi V. Risk of hippocampal metastases in small cell lung cancer patients at presentation and after cranial irradiation: a safety profile study for hippocampal sparing during prophylactic or therapeutic cranial irradiation. Int J Radiat Oncol Biol Phys 2015; 91:781-6. [PMID: 25752392 DOI: 10.1016/j.ijrobp.2014.12.026] [Citation(s) in RCA: 51] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2014] [Revised: 12/05/2014] [Accepted: 12/10/2014] [Indexed: 01/25/2023]
Abstract
PURPOSE Neurocognitive impairment (NI) in patients with small cell lung cancer (SCLC) after whole brain radiation treatment (WBRT) is a significant cause of morbidity. Hippocampal avoidance (HA) during WBRT may mitigate or prevent NI in such patients. However, this has not been tested in SCLC patients. The estimated risk of metastases in the HA region (HM) in patients with SCLC at diagnosis or after WBRT is unknown. Our study aimed to determine the risk of HM in patients with SCLC and to assess correlated clinical factors. METHODS AND MATERIALS Patients with SCLC who experienced brain metastases (BM) at presentation (de novo) or after WBRT treated at the Saskatoon Cancer Centre between 2005 and 2012 were studied. Relevant neuroimaging was independently reviewed by a neuroradiologist. HM was defined as metastases within 5 mm of the hippocampus. Logistic regression analysis was performed to assess correlation between various clinical variables and HM. RESULTS Seventy eligible patients were identified. Of 59 patients presenting with de novo BM, 3 patients (5%, 95% confidence interval [CI]: 0%-10.7%) had HM. Collectively there were 359 (range, 1-33) de novo BM with 3 (0.8%, 95% CI: 0%-1.7%) HM deposits. Twenty patients experienced progression of metastatic disease in the brain after WBRT. Of the 20 patients, only 1 patient (5%, 95% CI: 0%-14.5%) experienced HM. On logistic regression, no factors significantly correlated with HM. CONCLUSION The overall incidence of HM before or after WBRT in SCLC patients is low, providing preliminary support for the safety of HA during planned clinical trials of HA-WBRT for SCLC.
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Affiliation(s)
- Vijayananda Kundapur
- Saskatoon Cancer Center, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
| | - Tasha Ellchuk
- Department of Radiology, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Shahid Ahmed
- Saskatoon Cancer Center, College of Medicine, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
| | - Vinai Gondi
- Cadence Health Brain Tumor Center and Cadence Health Proton Center, Chicago, Illinois
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Whitsett TG, Inge LJ, Dhruv HD, Cheung PY, Weiss GJ, Bremner RM, Winkles JA, Tran NL. Molecular determinants of lung cancer metastasis to the central nervous system. Transl Lung Cancer Res 2015; 2:273-83. [PMID: 25806243 DOI: 10.3978/j.issn.2218-6751.2013.03.12] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2013] [Accepted: 03/29/2013] [Indexed: 12/19/2022]
Abstract
Lung cancer remains the leading cause of cancer-related mortality worldwide. The propensity for metastasis to the central nervous system (CNS) is a major clinical hurdle contributing to the low five-year survival rate of advanced disease. CNS metastases significantly outnumber primary brain tumors and carry a dismal prognosis in part due to the inability of therapeutic agents to cross the blood brain barrier. Standard treatment using radiation has been largely ineffective in improving mortality, suggesting the need for new agents targeting the critical metastatic drivers. The genetic and molecular events governing CNS metastasis from the lung are poorly understood at this time. This review highlights genetic events associated with CNS dissemination from the lung and molecular mechanisms associated with CNS metastasis. In vivo model systems that faithfully recapitulate escape from the lung and colonization of the CNS are described as tools for understanding the metastatic phenotype and for testing new therapeutic agents. A deeper understanding of the mechanisms of lung cancer metastasis to the CNS is needed to elucidate novel therapeutic avenues towards the improvement of the mortality associated with advanced stage lung cancer.
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Affiliation(s)
- Timothy G Whitsett
- Cancer and Cell Biology Division, The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA
| | - Landon J Inge
- Center for Thoracic and Esophageal Disease, Heart and Lung Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA
| | - Harshil D Dhruv
- Cancer and Cell Biology Division, The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA
| | - Philip Y Cheung
- Cancer and Cell Biology Division, The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA
| | - Glen J Weiss
- Cancer and Cell Biology Division, The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA ; ; Medical Oncology, Cancer Treatment Centers of America, Goodyear, AZ, USA
| | - Ross M Bremner
- Center for Thoracic and Esophageal Disease, Heart and Lung Institute, St. Joseph's Hospital and Medical Center, Phoenix, AZ, USA
| | - Jeffrey A Winkles
- Departments of Surgery and Physiology, Center for Vascular and Inflammatory Diseases and the Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Nhan L Tran
- Cancer and Cell Biology Division, The Translational Genomics Research Institute (TGen), Phoenix, AZ, USA
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Limited Small Cell Lung Cancer, An Early Stage Cancer that Should Receive the Attention of Experts. TUMORI JOURNAL 2015; 101:e34. [DOI: 10.5301/tj.5000262] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/14/2015] [Indexed: 11/20/2022]
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50
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Rule WG, Foster NR, Meyers JP, Ashman JB, Vora SA, Kozelsky TF, Garces YI, Urbanic JJ, Salama JK, Schild SE. Prophylactic cranial irradiation in elderly patients with small cell lung cancer: findings from a North Central Cancer Treatment Group pooled analysis. J Geriatr Oncol 2014; 6:119-26. [PMID: 25482023 DOI: 10.1016/j.jgo.2014.11.002] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2014] [Revised: 09/19/2014] [Accepted: 11/20/2014] [Indexed: 12/12/2022]
Abstract
OBJECTIVES To examine the efficacy of prophylactic cranial irradiation (PCI) in elderly patients with small cell lung cancer (SCLC) (≥70 years of age) from a pooled analysis of four prospective trials. MATERIALS & METHODS One hundred fifty-five patients with SCLC (limited stage, LSCLC, and extensive stage, ESCLC) participated in four phase II or III trials. Ninety-one patients received PCI (30 Gy/15 or 25 Gy/10) and 64 patients did not receive PCI. Survival was compared in a landmark analysis that included only patients who had stable disease or better in response to primary therapy. RESULTS Patients who received PCI had better survival than patients who did not receive PCI (median survival 12.0 months vs. 7.6 months, 3-year overall survival 13.2% vs. 3.1%, HR = 0.53 [95% CI 0.36-0.78], p = 0.001). On multivariate analysis of the entire cohort, the only factor that remained significant for survival was stage (ESCLC vs. LSCLC, p = 0.0072). In contrast, the multivariate analysis of patients who had ESCLC revealed that PCI was the sole factor associated with a survival advantage (HR = 0.47 [95% CI 0.24-0.93], p = 0.03). Grade 3 or higher adverse events (AEs) were significantly greater in patients who received PCI (71.4% vs. 47.5%, p = 0.0031), with non-neuro and non-heme being the specific AE categories most strongly correlated with PCI delivery. CONCLUSIONS PCI was associated with a significant improvement in survival for our entire elderly SCLC patient cohort on univariate analysis. Multivariate analysis suggested that the survival advantage remained significant in patients with ESCLC. PCI was also associated with a modest increase in grade 3 or higher AEs.
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Affiliation(s)
- William G Rule
- Department of Radiation Oncology, Mayo Clinic Arizona, USA.
| | - Nathan R Foster
- Section of Biomedical Statistics and Informatics, Mayo Clinic Rochester, USA
| | - Jeffrey P Meyers
- Section of Biomedical Statistics and Informatics, Mayo Clinic Rochester, USA
| | | | - Sujay A Vora
- Department of Radiation Oncology, Mayo Clinic Arizona, USA
| | | | | | - James J Urbanic
- Department of Radiation Oncology, Wake Forest School of Medicine, USA
| | - Joseph K Salama
- Department of Radiation Oncology, Duke University School of Medicine, USA
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