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Shao L, Dong Y, Jiang M, Song H, Qi Y, Guo L, Tian J, Wei S. Efficacy evaluation of prophylactic cranial irradiation for limited stage small‑cell lung cancer in the magnetic resonance imaging era: A meta‑analysis. Oncol Lett 2025; 29:123. [PMID: 39807106 PMCID: PMC11726293 DOI: 10.3892/ol.2025.14870] [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: 09/16/2024] [Accepted: 12/04/2024] [Indexed: 01/16/2025] Open
Abstract
The role of prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer (LS-SCLC) remains controversial in the era of magnetic resonance imaging (MRI). The present study aimed to evaluate the effectiveness of PCI in the treatment of LS-SCLC in the era of MRI. The PubMed, EMBASE and Cochrane Library databases were searched from the time of database creation until May 24, 2023, to identify clinical studies that evaluated the effectiveness of PCI in patients with LS-SCLC in the MRI era. The references of the obtained studies were also reviewed to identify clinical studies that were not discovered in the initial search. All studies were screened in accordance with the inclusion criteria, and the data were extracted and subjected to meta-analysis using STATA17.0. In total, 21 studies were included in the analysis. Notably, 10 studies only used brain MRI at baseline to confirm the absence of brain metastases (BMs; pre-chemoradiotherapy MRI group), 7 studies used brain MRI prior to PCI to confirm the absence of BMs (pre-PCI MRI group) and 4 studies used active surveillance in the form of brain MRI following PCI (MRI surveillance group). The results of the meta-analysis demonstrated that for all included patients, PCI was associated with a significant improvement in overall survival time [OS; hazard ratio (HR), 0.61; confidence interval (CI), 0.53-0.70] and progression-free survival (HR, 0.69; CI, 0.61-0.79), as well as a significant decrease in the rate of BM (HR, 0.59; CI, 0.50-0.70). Subgroup analyses revealed that PCI remained effective in improving OS and reducing the rate of BM in patients with LS-SCLC who did not have BMs confirmed via brain MRI performed at baseline or prior to PCI. However, in the MRI surveillance group, PCI failed to significantly improve the OS (HR, 0.65; CI, 0.41-1.05), despite significantly reducing the BM rate (HR, 0.6; CI, 0.45-0.8) of LS-SCLC. Collectively, the results of the present study demonstrated that PCI remained effective in improving OS and reducing the rate of BM in patients with LS-SCLC who had the absence of BM confirmed via brain MRI at baseline or prior to PCI. Additionally, in patients with LS-SCLC who had undergone active surveillance using brain MRI following PCI, the incidence of BM was reduced, while the OS was not significantly improved. However, additional randomized controlled clinical studies are required to verify these findings.
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Affiliation(s)
- Lihua Shao
- Department of Radiotherapy, Sun Yat-sen University Cancer Center Gansu Hospital, Lanzhou, Gansu 730050, P.R. China
| | - Yumei Dong
- Department of Radiotherapy, Sun Yat-sen University Cancer Center Gansu Hospital, Lanzhou, Gansu 730050, P.R. China
| | - Meiqiao Jiang
- School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730030, P.R. China
| | - Haixia Song
- Department of Radiotherapy, Sun Yat-sen University Cancer Center Gansu Hospital, Lanzhou, Gansu 730050, P.R. China
| | - Yuexiao Qi
- Department of Radiotherapy, Sun Yat-sen University Cancer Center Gansu Hospital, Lanzhou, Gansu 730050, P.R. China
| | - Liyun Guo
- Department of Radiotherapy, Sun Yat-sen University Cancer Center Gansu Hospital, Lanzhou, Gansu 730050, P.R. China
| | - Jinhui Tian
- School of Public Health, Lanzhou University, Lanzhou, Gansu 730030, P.R. China
| | - Shihong Wei
- Department of Radiotherapy, Sun Yat-sen University Cancer Center Gansu Hospital, Lanzhou, Gansu 730050, P.R. China
- School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou, Gansu 730030, P.R. China
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Daumas A, Bigarre C, Boucekine M, Zaccariotto A, Kaeppelin B, Mogenet A, Gouton E, Pluvy J, Tomasini P, Muracciole X, Benzekry S, Greillier L, Padovani L. Lack of Prophylactic Cranial Irradiation for Extensive Small-Cell Lung Cancer in Real Life, with the Emergence of Immunotherapy. Cancers (Basel) 2024; 16:4122. [PMID: 39682307 DOI: 10.3390/cancers16234122] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2024] [Revised: 11/22/2024] [Accepted: 12/01/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND Prophylactic cranial irradiation (PCI) is recommended to decrease the incidence of brain metastases (BM) in extensive-stage small-cell lung cancer (ESSCLC) without BM after response to chemotherapy. However, PCI is associated with significant neurocognitive effects, and new studies are debating its benefits. Moreover, the introduction of immunotherapy in the management of the disease has raised new questions, and there is a lack of data on PCI and immunotherapy. We report a single-center retrospective study evaluating the impact of omitting PCI from real-life treatment, including immunotherapy, of patients with ES-SCLC. METHODS We identified patients followed at APHM between January 2014 and January 2021 for ES-SCLC without BM with an indication for PCI. The main assessment criteria considered in this study were overall survival (OS) and brain metastasis-free survival (BMFS) between patients who received PCI and those who did not. RESULTS 56 patients were included, 25 receiving PCI and 31 without PCI. The median follow-up was 16 months. Eighteen patients received immunotherapy, mostly in the group without PCI (p = 0.024). The median OS and BMFS were, respectively, 11.7 and 13.4 months in patients with PCI, and 20.3 and 10.7 months in patients without PCI, without any significant statistical difference (p = 0.412, p = 0.336). The prognostic factors highlighted in multivariate analysis were initial performance status (PS) < 2 for OS (HR = 2.74 (IC95% [1.23; 6.13])) and monocyte lymphocyte ratio (MLR) < 0.12 for BMFS (HR = 1.21 (IC95% [1.01; 1.45])). A recursive partitioning analysis (RPA) found PS, immunotherapy, and age to be influential factors for OS but not PCI. CONCLUSIONS The clinical results of our study showed no benefit of PCI in terms of OS and BMFS for patients with ES-SCLC. This can be explained by the lack of benefit of PCI or by the introduction of immunotherapy.
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Affiliation(s)
- Alice Daumas
- Oncology Radiotherapy Department, Assistance Publique des Hôpitaux de Marseille, Aix-Marseille Université, 13005 Marseille, France
- COMPO, Inria Méditerranée, Cancer Research Center of Marseille, Inserm UMR1068, CNRS UMR7258, UM105, Aix-Marseille Université, 13273 Marseille, France
| | - Celestin Bigarre
- COMPO, Inria Méditerranée, Cancer Research Center of Marseille, Inserm UMR1068, CNRS UMR7258, UM105, Aix-Marseille Université, 13273 Marseille, France
| | - Mohamed Boucekine
- Unity of Research EA3279, Aix-Marseille Université, 13007 Marseille, France
| | - Audrey Zaccariotto
- Oncology Radiotherapy Department, Assistance Publique des Hôpitaux de Marseille, Aix-Marseille Université, 13005 Marseille, France
| | - Bertrand Kaeppelin
- Oncology Radiotherapy Department, Assistance Publique des Hôpitaux de Marseille, Aix-Marseille Université, 13005 Marseille, France
| | - Alice Mogenet
- Multidisciplinary Oncology and Therapeutic Innovations Department, Assistance Publique des Hôpitaux de Marseille, Aix-Marseille Université, 13005 Marseille, France
| | - Etienne Gouton
- Multidisciplinary Oncology and Therapeutic Innovations Department, Assistance Publique des Hôpitaux de Marseille, Aix-Marseille Université, 13005 Marseille, France
| | - Johan Pluvy
- Multidisciplinary Oncology and Therapeutic Innovations Department, Assistance Publique des Hôpitaux de Marseille, Aix-Marseille Université, 13005 Marseille, France
| | - Pascale Tomasini
- Multidisciplinary Oncology and Therapeutic Innovations Department, Assistance Publique des Hôpitaux de Marseille, Aix-Marseille Université, 13005 Marseille, France
| | - Xavier Muracciole
- Oncology Radiotherapy Department, Assistance Publique des Hôpitaux de Marseille, Aix-Marseille Université, 13005 Marseille, France
- COMPO, Inria Méditerranée, Cancer Research Center of Marseille, Inserm UMR1068, CNRS UMR7258, UM105, Aix-Marseille Université, 13273 Marseille, France
| | - Sebastien Benzekry
- COMPO, Inria Méditerranée, Cancer Research Center of Marseille, Inserm UMR1068, CNRS UMR7258, UM105, Aix-Marseille Université, 13273 Marseille, France
| | - Laurent Greillier
- COMPO, Inria Méditerranée, Cancer Research Center of Marseille, Inserm UMR1068, CNRS UMR7258, UM105, Aix-Marseille Université, 13273 Marseille, France
- Multidisciplinary Oncology and Therapeutic Innovations Department, Assistance Publique des Hôpitaux de Marseille, Aix-Marseille Université, 13005 Marseille, France
| | - Laetitia Padovani
- Oncology Radiotherapy Department, Assistance Publique des Hôpitaux de Marseille, Aix-Marseille Université, 13005 Marseille, France
- Scientific Research National Center (CNRS), Institute of Neurophysiopathology, Aix-Marseille University, 13005 Marseille, France
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Yılmaz F, Yaşar S, Tatar ÖD, Yıldırım HÇ, Güven DC, Akyıldız A, Chalabiyev E, Aktaş BY, Arık Z, Erman M. Bi-weekly irinotecan is an effective and convenient regimen in the treatment of relapsed or refractory small cell lung cancer. BMC Cancer 2024; 24:1218. [PMID: 39354432 PMCID: PMC11443928 DOI: 10.1186/s12885-024-12935-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2024] [Accepted: 09/11/2024] [Indexed: 10/03/2024] Open
Abstract
BACKGROUND Despite initial dramatic responses, metastatic small cell lung cancer (SCLC) invariably recurs. Irinotecan is one of the active agents for patients with recurrent SCLC. In the second line, weekly or three-weekly irinotecan regimens have been adopted, however, the optimal dose and schedule is not defined. In our institution, we use a bi-weekly regimen of irinotecan. In this study, we aimed to investigate the safety and efficacy of the bi-weekly irinotecan in the second- or third-line treatment of SCLC patients. METHODS The study population consisted of advanced stage SCLC patients who were followed at Hacettepe University Cancer Institute between January 2007 and March 2021 and received salvage irinotecan 180 mg/m2 every two weeks, following progression after platinum-etoposide treatment. RESULTS One hundred patients were included. At diagnosis, nineteen patients (19%) had limited stage and 81 patients (81%) had extensive stage SCLC. Objective response rates (ORR) were 44.6% and 46.2% for patients who received irinotecan treatment in second line, and in third line, respectively. Seventeen percent of all the patients had grade 3 and above adverse events during irinotecan treatment. In our study, 45.8% of patients were able to complete at least 6 cycles of irinotecan treatment and 69.8% were able to receive at least 3 cycles of irinotecan treatment without any dose interruption or reduction. CONCLUSIONS Irinotecan 180 mg/m2 every two weeks appears to be safe and effective in the 2nd- and 3rd-line treatment of advanced stage SCLC. Bi-weekly administration allows G-CSF prophylaxis in between doses, leading to an uninterrupted administration.
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Affiliation(s)
- Feride Yılmaz
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye.
| | - Serkan Yaşar
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
| | | | - Hasan Çağrı Yıldırım
- Department of Medical Oncology, Niğde Training and Research Hospital, Niğde, Türkiye
| | - Deniz Can Güven
- Department of Medical Oncology, Elazığ Fethi Sekin City Hospital, Elazığ, Türkiye
| | - Arif Akyıldız
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
| | - Elvin Chalabiyev
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
| | - Burak Yasin Aktaş
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
| | - Zafer Arık
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
| | - Mustafa Erman
- Department of Medical Oncology, Hacettepe University Cancer Institute, Ankara, Türkiye
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Tang L, Tian G, Li N. Current dilemma and future directions over prophylactic cranial irradiation in SCLC: a systematic review in MRI and immunotherapy era. Front Oncol 2024; 14:1382220. [PMID: 39139283 PMCID: PMC11319250 DOI: 10.3389/fonc.2024.1382220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Accepted: 07/15/2024] [Indexed: 08/15/2024] Open
Abstract
Small cell lung cancer (SCLC) is the most malignant pathological type of lung cancer with the highest mortality, and the incidence of brain metastasis (BM) is in high frequency. So far, prophylactic cranial irradiation (PCI) has been suggested as an effective treatment for preventing brain metastasis of SCLC. PCI has long been applied to limited-stage SCLC (LS-SCLC) patients who have achieved complete remission after radiotherapy and chemotherapy as a standard treatment. However, the neurocognitive decline is a major concern surrounding PCI. New therapeutic approaches targeting PCI-induced neurotoxicity, including hippocampal protection or memantine, have been increasingly incorporated into the therapeutic interventions of PCI. Helical tomotherapy, RapidArc, and Volumetric-modulated arc therapy (VMAT) with a head-tilting baseplate are recommended for hippocampal protection. Besides, in the MRI and immunotherapy era, the significance of PCI in SCLC patients is controversial. SCLC patients with PCI should be recruited in clinical trials since this is the only way to improve the existing standard of care. This review summarizes the current therapeutic strategy and dilemma over PCI for SCLC, providing a theoretical basis for clinical decision-making and suggestions for PCI practice in clinical.
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Affiliation(s)
| | | | - Nan Li
- Department of Radiation Oncology, the First Hospital of China Medical University, Shenyang, China
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Gaebe K, Erickson AW, Li AY, Youssef AN, Sharma B, Chan KK, Lok BH, Das S. Re-examining prophylactic cranial irradiation in small cell lung cancer: a systematic review and meta-analysis. EClinicalMedicine 2024; 67:102396. [PMID: 38261885 PMCID: PMC10796984 DOI: 10.1016/j.eclinm.2023.102396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 12/07/2023] [Accepted: 12/11/2023] [Indexed: 01/25/2024] Open
Abstract
Background Patients with small cell lung cancer (SCLC) are at high risk for brain metastases. Prophylactic cranial irradiation (PCI) is recommended in this population to reduce the incidence of brain metastases and prolong survival. We aimed to assesses the efficacy of PCI in this population in the era of routine brain imaging. To our knowledge, this is the first systematic review and meta-analysis to examine the use among patients who were radiographically confirmed not to have brain metastases after completion of first-line therapy. Methods In this systematic review and meta-analysis, cohort studies and controlled trials reporting on the use of PCI for patients SCLC were identified in EMBASE, MEDLINE, CENTRAL, and grey literature sources. The literature search was conducted on November 12, 2023. Summary data were extracted. Random-effects meta-analyses pooled hazard ratios (HR) for the primary outcome of overall survival between PCI and no intervention groups. This study is registered with the Open Science Framework, DOI:10.17605/OSF.IO/BC359, and PROSPERO, CRD42021249466. Findings Of 4318 identified records, 223 were eligible for inclusion. 109 reported on overall survival in formats amenable to meta-analysis; PCI was associated with longer survival in all patients with SCLC (HR 0.59; 95% CI, 0.55-0.63; p < 0.001; n = 56,770 patients), patients with limited stage disease (HR 0.60; 95% CI, 0.55-0.65; p < 0.001; n = 78 studies; n = 27,137 patients), and patients with extensive stage disease (HR 0.59; 95% CI, 0.51-0.70; p < 0.001; n = 28 studies; n = 26,467 patients). Between-study heterogeneity was significant when pooled amongst all studies (I2 = 73.6%; 95% CI 68.4%-77.9%). Subgroup analysis did not reveal sources of heterogeneity. In a subgroup analysis on studies that used magnetic resonance imaging to exclude presence of brain metastases at restaging among all patients, overall survival did not differ significantly between patients who did or did not receive PCI (HR 0.74; 95% CI, 0.52-1.05; p = 0.08; n = 9 studies; n = 1384 patients). Interpretation Our findings suggested that administration of PCI is associated with a survival benefit, but not when considering studies that radiographically confirmed absence of brain metastases, suggesting that the survival benefit conferred by PCI might be therapeutic rather than prophylactic. Funding No funding.
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Affiliation(s)
- Karolina Gaebe
- Institute of Medical Science, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada
| | - Anders W. Erickson
- Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada
| | - Alyssa Y. Li
- Institute of Medical Science, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada
| | - Andrew N. Youssef
- Department of Laboratory Medicine and Pathobiology, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada
| | - Bhagyashree Sharma
- Institute of Medical Science, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada
| | - Kelvin K.W. Chan
- Division of Medical Oncology, Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada
| | - Benjamin H. Lok
- Institute of Medical Science, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Sunit Das
- Institute of Medical Science, Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, Ontario, Canada
- Division of Neurosurgery, St. Michael's Hospital, University of Toronto, 30 Bond Street, Toronto, Ontario, Canada
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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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Yang F, Zhao H. Progress in radiotherapy for small-cell lung cancer. PRECISION RADIATION ONCOLOGY 2023; 7:207-217. [PMID: 40337202 PMCID: PMC11935219 DOI: 10.1002/pro6.1205] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2023] [Revised: 05/28/2023] [Accepted: 06/25/2023] [Indexed: 05/09/2025] Open
Abstract
Small-cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor that is prone to spread extensively. Compared to non-small-cell lung cancer (NSCLC), SCLC treatment progresses slowly. Although SCLC is highly sensitive to chemotherapy during the initial treatment, most patients still experience resistance and recurrence after receiving chemotherapy. A meta-analysis demonstrated that thoracic radiotherapy (TRT) improves overall survival in SCLC. The results of the CALGB and CONVERT trials provide evidence for the efficacy of once-daily high-dose TRT. TRT at 60 Gy administered twice daily significantly improved survival without increasing toxicity. The long-standing debate over the optimal timing of radiotherapy has not been fully resolved. SBRT has excellent local control rates and is a safe and effective treatment option for patients with stage I or II SCLC. Prophylactic cranial irradiation (PCI) is used to reduce treatment-related neurotoxicity to the extent that there has been a recent discussion on whether magnetic resonance imaging (MRI) monitoring can replace PCI. Radiotherapy combined with immunotherapy significantly improves the survival rate of patients with NSCLC; however, its clinical effectiveness has not been systematically explored in patients with SCLC. Therefore, we summarize the evolving therapeutic strategies, (TRT for limited stage-SCLC and consolidative TRT for extensive stage-SCLC) and improved radiotherapy techniques (role of SBRT in stage I or II node-negative SCLC, progress of PCI, and stereotactic radiosurgery), and discuss the possibilities and prospects of radiotherapy combined with immunotherapy for SCLC.
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Affiliation(s)
- Fujun Yang
- Key Laboratory of Precision Diagnosis and Treatment in Oncology of WeihaiDepartment of OncologyWeihai Municipal HospitalWeihaiShandongChina
| | - Huan Zhao
- Key Laboratory of Precision Diagnosis and Treatment in Oncology of WeihaiDepartment of OncologyWeihai Municipal HospitalWeihaiShandongChina
- The Second Medical College of Binzhou Medical UniversityBinzhou Medical UniversityYantaiShandongChina
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Li H, Zhao Y, Ma T, Shao H, Wang T, Jin S, Liu Z. Radiotherapy for extensive-stage small-cell lung cancer in the immunotherapy era. Front Immunol 2023; 14:1132482. [PMID: 37701437 PMCID: PMC10493776 DOI: 10.3389/fimmu.2023.1132482] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2022] [Accepted: 08/01/2023] [Indexed: 09/14/2023] Open
Abstract
Currently, chemoimmunotherapy is the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, only 0.8%-2.5% of the patients presented complete response after chemoimmunotherapy. Considering that ES-SCLC is highly sensitive to radiotherapy, the addition of radiotherapy after first-line treatment for ES-SCLC could further improve local control, which may be beneficial for patients' survival. Prior studies have shown that consolidative thoracic radiotherapy (cTRT) can decrease disease progression and improve overall survival in patients with ES-SCLC who respond well to chemotherapy. However, the efficacy and safety of cTRT in the immunotherapy era remain unclear owing to a lack of prospective studies. Prophylactic cranial irradiation (PCI) has been shown to decrease brain metastasis (BM) and prolong survival in patients with limited-stage SCLC in previous reports. However, according to current guidelines, PCI is not commonly recommended for ES-SCLC. Immunotherapy has the potential to reduce the incidence of BM. Whether PCI can be replaced with regular magnetic resonance imaging surveillance for ES-SCLC in the era of immunotherapy remains controversial. Whole brain radiation therapy (WBRT) is the standard treatment for BM in SCLC patients. Stereotactic radiosurgery (SRS) has shown promise in the treatment of limited BM. Considering the potential of immunotherapy to decrease BM, it is controversial whether SRS can replace WBRT for limited BM in the immunotherapy era. Additionally, with the addition of immunotherapy, the role of palliative radiotherapy may be weakened in patients with asymptomatic metastatic lesions. However, it is still indispensable and urgent for patients with obvious symptoms of metastatic disease, such as spinal cord compression, superior vena cava syndrome, lobar obstruction, and weight-bearing metastases, which may critically damage the quality of life and prognosis. To improve the outcome of ES-SCLC, we discuss the feasibility of radiotherapy, including cTRT, PCI, WBRT/SRS, and palliative radiotherapy with immunotherapy based on existing evidence, which may offer specific prospects for further randomized trials and clinical applications.
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Affiliation(s)
- Huanhuan Li
- Department of Radiation Oncology, The Second Affiliated Hospital of Jilin University, Changchun, China
| | - Yangzhi Zhao
- Department of Hematology, The First Hospital of Jilin University, Changchun, China
| | - Tiangang Ma
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Jilin University, Changchun, China
| | - Hao Shao
- Department of Radiation Oncology, The Second Affiliated Hospital of Jilin University, Changchun, China
| | - Tiejun Wang
- Department of Radiation Oncology, The Second Affiliated Hospital of Jilin University, Changchun, China
| | - Shunzi Jin
- NHC Key Laboratory of Radiobiology, Jilin University, Changchun, China
| | - Zhongshan Liu
- Department of Radiation Oncology, The Second Affiliated Hospital of Jilin University, Changchun, China
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9
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Wang Z, Chen L, Sun L, Cai F, Yang Q, Hu X, Fu Q, Chen W, Li P, Li W. Prophylactic cranial irradiation for extensive stage small cell lung cancer: a meta-analysis of randomized controlled trials. Front Oncol 2023; 13:1086290. [PMID: 37265787 PMCID: PMC10229841 DOI: 10.3389/fonc.2023.1086290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Accepted: 04/14/2023] [Indexed: 06/03/2023] Open
Abstract
BACKGROUND Previous studies have demonstrated that prophylactic cranial irradiation (PCI) could reduce the risk of brain metastases and prolong the overall survival (OS) of patients with small cell lung cancer (SCLC). However, it remains controversial whether the efficacy and safety of PCI would be subjected to the different characteristics of patients with extensive stage of SCLC. This meta-analysis aims to evaluate the efficacy and safety of PCI in patients with extensive stage SCLC. METHODS PubMed, Embase, and the Cochrane Library were searched for relevant studies from inception to May, 2021. Hazard ratios (HRs) were used to measure the OS and progression-free survival (PFS), and relative risks (RRs) were employed to calculate the incidence of brain metastases, survival rate, and adverse events. Summary results were pooled using random-effect models. RESULTS There were 1215 articles identified, and 15 trials were included, with a total of 1,623 participants. Patients who received PCI did not result in significantly improved OS [HR=0.87, 95%CI (0.70, 1.08) p=0.417] and PFS [HR=0.81, 95%CI (0.69, 0.95) p=0.001], compared with those who did not receive PCI, while patients who received PCI had a significantly decreased incidence of brain metastases [RR=0.57, 95%CI (0.45, 0.74), p<0.001]. PCI group showed no improvements in 2-year (RR=1.03, p=0.154), 3-year (RR=0.97, p=0.072), 4-year (RR=0.71, p=0.101) and 5-year survival rates (RR=0.32, p=0.307), compared with non-PCI group, whereas the overall RR indicated that PCI was associated with a higher 1-year survival rate [RR=1.46, 95%CI (1.08, 1.97), p=0.013]. In addition, PCI treatment was shown to be associated with increased incidence of adverse events, including fatigue, dermatitis, anorexia, nausea, vomiting, malaise, and cognitive impairment. CONCLUSION This meta-analysis suggests that PCI can reduce the incidence of brain metastases in extensive stage SCLC. Although PCI has no significant effect on the OS, it improves 1-year survival in patients with extensive stage SCLC. However, PCI does not significantly affect 2,3,4,5-year survival and may result in a significantly increased risk of adverse events.
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Affiliation(s)
- Ziyi Wang
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Liang Chen
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Lu Sun
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Feng Cai
- Department of Radiation Oncology, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Qiwei Yang
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Xiaohai Hu
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Qiang Fu
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Weiyang Chen
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Peiwei Li
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China
| | - Wenya Li
- Department of Thoracic Surgery, The First Hospital of China Medical University, Shenyang, Liaoning, China
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Sun A, Abdulkarim B, Blais N, Greenland J, Louie AV, Melosky B, Schellenberg D, Snow S, Liu G. Use of radiation therapy among patients with Extensive-stage Small-cell lung cancer receiving Immunotherapy: Canadian consensus recommendations. Lung Cancer 2023; 179:107166. [PMID: 36944282 DOI: 10.1016/j.lungcan.2023.03.002] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2022] [Revised: 02/23/2023] [Accepted: 03/06/2023] [Indexed: 03/11/2023]
Abstract
OBJECTIVES Thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) are commonly used in the management of extensive-stage small-cell lung cancer (ES-SCLC); however, Phase III trials of first-line immunotherapy often excluded these options. Guidance is needed regarding appropriate use of TRT, PCI, and magnetic resonance imaging (MRI) surveillance while new data are awaited. MATERIALS AND METHODS In two web-based meetings, a pan-Canadian expert working group of five radiation oncologists and four medical oncologists addressed eight clinical questions regarding use of radiation therapy (RT) and MRI surveillance among patients with ES-SCLC receiving immunotherapy. A targeted literature review was conducted using PubMed and conference proceedings to identify recent (January 2019-April 2022) publications in this setting. Fifteen recommendations were developed; online voting was conducted to gauge agreement with each recommendation. RESULTS After considering recently available evidence across lung cancer populations and clinical experience, the experts recommended that all patients with a response to chemo-immunotherapy, good performance status (PS), and limited metastases be considered for consolidation TRT (e.g., 30 Gy in 10 fractions). When considered appropriate after multidisciplinary team discussion, TRT can be initiated during maintenance immunotherapy. All patients who respond to concurrent chemo-immunotherapy should undergo restaging with brain MRI to guide decision-making regarding PCI versus MRI surveillance alone. MRI surveillance should be conducted for two years after response to initial therapy. PCI (e.g., 25 Gy in 10 fractions or 20 Gy in 5 fractions) can be considered for patients without central nervous system involvement who have a response to chemo-immunotherapy and good PS. Concurrent treatment with PCI and immunotherapy or with TRT, PCI, and immunotherapy is appropriate after completion of initial therapy. All recommendations were agreed upon unanimously. CONCLUSIONS These consensus recommendations provide practical guidance regarding appropriate use of RT and immunotherapy in ES-SCLC while awaiting new clinical trial data.
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Affiliation(s)
- Alexander Sun
- Princess Margaret Cancer Centre, 700 University Avenue, Toronto, ON M5G 1Z5, Canada.
| | - Bassam Abdulkarim
- McGill University Health Centre, McGill University, 1001 Decarie Boulevard, Montréal, QC H4A 3J1, Canada.
| | - Normand Blais
- Centre Hospitalier de l'Université de Montréal, University of Montréal, 1051 Rue Sanguinet, Montréal, QC H2X 3E4, Canada.
| | - Jonathan Greenland
- Eastern Health, 300 Prince Philip Drive, St. John's, NL A1B 3V6, Canada.
| | - Alexander V Louie
- Sunnybrook Health Sciences Centre, 2075 Bayview Avenue, Toronto, ON M4N 3M5, Canada.
| | - Barbara Melosky
- BC Cancer-Vancouver Centre, 600 W 10th Avenue, Vancouver, BC V5Z 4E6, Canada.
| | | | - Stephanie Snow
- QEII Health Sciences Centre, Dalhousie University, 5788 University Avenue, Halifax, NS B3H 1V8, Canada.
| | - Geoffrey Liu
- Princess Margaret Cancer Centre, University Health Network, 610 University Avenue, Toronto, ON M5G 2M9, Canada.
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Wu Q, Chen M, Peng F, Zhang Q, Kong Y, Bao Y, Xu Y, Hu X, Chen M. A study of the prognosis of patients with limited-stage small cell lung cancer who did or did not receive prophylactic cranial irradiation after effective chemoradiotherapy. Front Oncol 2023; 13:1118371. [PMID: 37035198 PMCID: PMC10076622 DOI: 10.3389/fonc.2023.1118371] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2022] [Accepted: 03/09/2023] [Indexed: 04/11/2023] Open
Abstract
Objective To investigate the prognosis of patients with LS-SCLC who responded to chest chemoradiotherapy but did not receive PCI. Methods A retrospective analysis was conducted on LS-SCLC patients who had achieved complete remission (CR) or partial remission (PR) after definitive chemoradiotherapy but did not receive PCI. The survival rates were calculated using Kaplan-Meier method. The prognosis was analyzed using Cox proportional hazard regression model. The main endpoint was OS. Results Of the 500 patients with LS-SCLC admitted between June 2002 and January 2018, 327 achieved CR or PR after definitive chest chemoradiotherapy, 103 did not receive PCI, and 63 of them developed brain metastases (BM). The 1-year and 3-year OS rates in PCI group were 87.5% and 42.3% respectively, versus 70.4% and 20.9% for non-PCI group(P=0.002). The median survival time after BM was 8.7 months (range: 0.3-48.7), and 3-year OS rate was 15.0%, the median survival time of patients without BM was 20.1 months (range: 2.9-79.4), and 3-year OS was 33.4% (P=0.014). Patients with BM were subsequently treated with palliative therapy. Multivariate analysis showed that compared with no treatment, brain radiotherapy alone (HR: 0.131, 95%CI: 0.035-0.491, P=0.003) and radiotherapy combined with chemotherapy (HR: 0.039, 95%CI: 0.008-0.194, P<0.001) significantly reduced the risk of death. Multiple BM (HR: 2.391, 95%CI: 1.082-5.285, P=0.031) was an independent adverse prognostic factor for OS. Conclusion LS-SCLC patients who achieved good response after chest chemoradiotherapy without receiving PCI were prone to develop BM and have a poor prognosis. Multiple BM was an independent adverse prognostic factor. PCI remains the standard of care for LS-SCLC patients.
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Affiliation(s)
- Qing Wu
- The Second Clinical Medical College of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
- Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang, China
| | - Mengyuan Chen
- Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang, China
| | - Fang Peng
- Department of Radiotherapy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Qun Zhang
- Department of Radiotherapy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yue Kong
- Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang, China
| | - Yong Bao
- Department of Radiotherapy, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Yujin Xu
- Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang, China
| | - Xiao Hu
- Department of Thoracic Radiotherapy, Zhejiang Cancer Hospital, Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Zhejiang Key Laboratory of Radiation Oncology, Hangzhou, Zhejiang, China
- *Correspondence: Xiao Hu, ; Ming Chen,
| | - Ming Chen
- Department of Radiotherapy, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, China
- *Correspondence: Xiao Hu, ; Ming Chen,
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12
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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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13
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Luciani A, Blasi M, Provenzano L, Zonato S, Ferrari D. Recent advances in small cell lung cancer: the future is now? Minerva Endocrinol (Torino) 2022; 47:460-474. [PMID: 33331739 DOI: 10.23736/s2724-6507.20.03213-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
Small cell lung cancer is a relevant clinical issue as it is a highly malignant cancer, often diagnosed in advanced stage. Similarly to non-small cell lung cancer, tobacco smoking is currently the main risk factor. Its incidence, at least in males, has declined over the past decades, due to the worldwide decreased percentage of active smokers. The typical small cells of this tumor type are characterized by a high Proliferation Index, chromosomal deletions such as 3p(14-23) involving the tumor-suppressor gene FHIT, alterations of the MYC or Notch family proteins and the frequent expression of neuroendocrine markers. The combination of thoracic radiotherapy and chemotherapy is the standard treatment for limited stage disease, while platinum-based chemotherapy is the most effective choice for extensive stage disease. Unfortunately, whatever chemotherapy is used, the results are disappointing. No regimen has proved to be effective in the long run, indeed small cell lung cancer rapidly progresses after a frequent initial strong response, and the mortality rate remains still high. The advent of immunotherapy is actually changing the landscape in oncology. As well as in other cancers, recent trials have demonstrated the efficacy of the combination of immune checkpoint inhibitors and chemotherapy, opening new perspectives for the future of our patients.
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Affiliation(s)
- Andrea Luciani
- Unit of Medical Oncology, San Paolo Hospital, Milan, Italy -
| | - Miriam Blasi
- Unit of Medical Oncology, San Paolo Hospital, Milan, Italy
| | | | - Sabrina Zonato
- Unit of Medical Oncology, San Paolo Hospital, Milan, Italy
| | - Daris Ferrari
- Unit of Medical Oncology, San Paolo Hospital, Milan, Italy
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Merie R, Gee H, Hau E, Vinod S. An Overview of the Role of Radiotherapy in the Treatment of Small Cell Lung Cancer - A Mainstay of Treatment or a Modality in Decline? Clin Oncol (R Coll Radiol) 2022; 34:741-752. [PMID: 36064636 DOI: 10.1016/j.clon.2022.08.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/16/2022] [Accepted: 08/10/2022] [Indexed: 01/31/2023]
Abstract
AIMS Small cell lung cancer (SCLC) accounts for about 15% of all lung cancers. Chemotherapy, immunotherapy and radiotherapy all play important roles in the management of SCLC. The aim of this study was to provide a comprehensive overview of the role and evidence of radiotherapy in the cure and palliation of SCLC. MATERIALS AND METHODS The search strategy included a search of the PubMed database, hand searches, reference lists of relevant review articles and relevant published abstracts. CLINICALTRIALS gov was also queried for relevant trials. RESULTS Thoracic radiotherapy improves overall survival in limited stage SCLC, but the timing and dose remain controversial. The role of thoracic radiotherapy in extensive stage SCLC with immunotherapy is the subject of several ongoing trials. Current evidence supports the use of prophylactic cranial irradiation (PCI) for limited stage SCLC but the evidence is equivocal in extensive stage SCLC. Whole brain radiotherapy is well established for the treatment of brain metastases but evidence is rapidly accumulating for the use of stereotactic radiosurgery. Further studies will define the role of PCI, whole brain radiotherapy and hippocampal avoidant PCI in the immunotherapy era. CONCLUSION Radiotherapy is an essential component in the multimodality management of SCLC. Technological advances have allowed safer delivery of radiotherapy with reduced toxicities. Discussion at multidisciplinary team meetings is important to ensure radiotherapy is considered and offered in appropriate patients.
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Affiliation(s)
- R Merie
- Icon Cancer Centre, Concord Repatriation General Hospital, Concord, NSW, Australia; South West Sydney Clinical Campuses, University of NSW, Liverpool, NSW, Australia.
| | - H Gee
- Sydney West Radiation Oncology Network (SWRON), Sydney, NSW, Australia; Sydney Medical School, Westmead Hospital, University of Sydney, Sydney, NSW, Australia; Children's Medical Research Institute (CMRI), University of Sydney, Sydney, NSW, Australia
| | - E Hau
- Sydney West Radiation Oncology Network (SWRON), Sydney, NSW, Australia; Sydney Medical School, Westmead Hospital, University of Sydney, Sydney, NSW, Australia; The Westmead Institute for Medical Research (WIMR), Westmead, NSW, Australia
| | - S Vinod
- South West Sydney Clinical Campuses, University of NSW, Liverpool, NSW, Australia; Cancer Therapy Centre, Liverpool Hospital, Liverpool, NSW, Australia; Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia
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15
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Hou Q, Sun B, Yao N, Liang Y, Cao X, Wei L, Cao J. Construction of Brain Metastasis Prediction Model and Optimization of Prophylactic Cranial Irradiation Selection for Limited-Stage Small-Cell Lung Cancer. Cancers (Basel) 2022; 14:cancers14194906. [PMID: 36230830 PMCID: PMC9563012 DOI: 10.3390/cancers14194906] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Revised: 09/30/2022] [Accepted: 10/05/2022] [Indexed: 11/21/2022] Open
Abstract
Prophylactic cranial irradiation (PCI), as an essential part of the treatment of limited-stage small-cell lung cancer (LS-SCLC), inevitably leads to neurotoxicity. This study aimed to construct a brain metastasis prediction model and identify low-risk patients to avoid PCI; 236 patients with LS-SCLC were retrospectively analyzed and divided into PCI (63 cases) and non-PCI groups (173 cases). The nomogram was developed based on variables determined by univariate and multivariate analyses in the non-PCI group. According to the cutoff nomogram score, all patients were divided into high- and low-risk cohorts. A log-rank test was used to compare the incidence of brain metastasis between patients with and without PCI in the low-risk and high-risk groups, respectively. The nomogram included five variables: chemotherapy cycles (ChT cycles), time to radiotherapy (RT), lactate dehydrogenase (LDH), pro-gastrin-releasing peptide precursor (ProGRP), and lymphocytes−monocytes ratio (LMR). The area under the receiver operating characteristics (AUC) of the nomogram was 0.763 and 0.782 at 1 year, and 0.759 and 0.732 at 2 years in the training and validation cohorts, respectively. Based on the nomogram, patients were divided into high- and low-risk groups with a cutoff value of 165. In the high-risk cohort, the incidence of brain metastasis in the non-PCI group was significantly higher than in the PCI group (p < 0.001), but there was no difference in the low-risk cohort (p = 0.160). Propensity score-matching (PSM) analysis showed similar results; the proposed nomogram showed reliable performance in assessing the individualized brain metastasis risk and has the potential to become a clinical tool to individualize PCI treatment for LS-SCLC.
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16
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Gordhandas S, Schlappe BA, Zhou Q, Iasonos A, Leitao MM, Park KJ, de Brot L, Alektiar KM, Sabbatini PJ, Aghajanian CA, Friedman C, Zivanovic O, O'Cearbhaill RE. Small cell neuroendocrine carcinoma of the cervix: Analysis of prognostic factors and patterns of metastasis. Gynecol Oncol Rep 2022; 43:101058. [PMID: 35967833 PMCID: PMC9365998 DOI: 10.1016/j.gore.2022.101058] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Revised: 07/28/2022] [Accepted: 07/31/2022] [Indexed: 11/30/2022] Open
Abstract
A two-tier system (limited- or extensive-stage) has been used for small cell neuroendocrine carcinomas of the cervix. Concordance probability estimates found that the 2018 FIGO staging system predicted outcome better than the two-tier system. 38% of patients had metastases at initial diagnosis, and an additional 38% at subsequent recurrence. 38 patients (60%) had brain imaging: 1 (3%) had brain metastasis at diagnosis and 8 (21%) at subsequent recurrence. Providers should have a low threshold for brain imaging in patients with advanced disease or neurologic symptoms. Objectives To describe characteristics and outcomes of patients with small cell neuroendocrine carcinoma of the cervix (SCNCC) and determine the staging system most predictive of outcome—the two-tier (limited-stage [LS] vs. extensive-stage [ES]) or International Federation of Gynecology and Obstetrics (FIGO) staging system. Methods Patients with SCNCC evaluated at our institution from 1/1/1990–6/30/2021 were included. Medical records were reviewed for variables of interest. Appropriate statistical tests were performed to determine associations. Survival curves were created using the Kaplan-Meier method. Concordance probability estimates (CPEs) were calculated to evaluate the prediction probability of the staging systems. Results Of 63 patients, 41 had LS and 22 ES SCNCC. Patients with ES disease were significantly older than those with LS disease (median, 54 and 37 years, respectively; p < 0.001). Smoking status, race, and history of HPV were not associated with stage or outcomes. Forty-eight patients had metastatic disease (24 [50%] at initial diagnosis). The most common first sites of metastasis were lung (n = 20/48, 42%), lymph nodes (n = 19/48, 40%), and liver (n = 13/48, 27%). Nine patients had brain metastasis (8 symptomatic at recurrence; 1 asymptomatic at initial diagnosis). Both staging systems were associated with progression-free and overall survival. Adjusted CPE found the FIGO staging system was more predictive of outcomes than the two-tier staging system. Conclusions Providers should have a low threshold to obtain brain imaging for patients with SCNCC, especially in the presence of visceral metastases. FIGO staging should be used to classify SCNCC. Further research is necessary to understand prognostic factors of this rare disease.
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Affiliation(s)
- Sushmita Gordhandas
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Brooke A. Schlappe
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Currently at: Gynecologic Oncology, Department of Surgery, Aurora Health Care, Milwaukee, WI, USA
| | - Qin Zhou
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Alexia Iasonos
- Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Mario M. Leitao
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of OB/GYN, Weill Cornell Medical College, New York, NY, USA
| | - Kay J. Park
- Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Louise de Brot
- A.C. Camargo Cancer Center, Anatomic Pathology Department, São Paulo, Brazil
| | - Kaled M. Alektiar
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA
| | - Paul J. Sabbatini
- Gynecologic Medical Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Medicine, Weill Cornell Medical College, New York, NY, USA
| | - Carol A. Aghajanian
- Gynecologic Medical Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Medicine, Weill Cornell Medical College, New York, NY, USA
| | - Claire Friedman
- Gynecologic Medical Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Medicine, Weill Cornell Medical College, New York, NY, USA
| | - Oliver Zivanovic
- Gynecology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of OB/GYN, Weill Cornell Medical College, New York, NY, USA
| | - Roisin E O'Cearbhaill
- Gynecologic Medical Oncology, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA
- Department of Medicine, Weill Cornell Medical College, New York, NY, USA
- Corresponding author: Gynecology Medical Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275, York Avenue, New York, NY 10065, USA.
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Schlick B, Shields MD, Marin-Acevedo JA, Patel I, Pellini B. Immune Checkpoint Inhibitors and Chemoradiation for Limited-Stage Small Cell Lung Cancer. Curr Treat Options Oncol 2022; 23:1104-1120. [PMID: 35716328 PMCID: PMC9345799 DOI: 10.1007/s11864-022-00989-7] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/15/2022] [Indexed: 12/01/2022]
Abstract
OPINION STATEMENT Limited-stage small cell lung cancer (LS-SCLC) is a potentially curable disease. However, most patients develop disease relapse shortly after definitive treatment. The landmark trials IMpower133 and CASPIAN demonstrated a survival benefit with the addition of immunotherapy to first-line platinum/etoposide for extensive-stage small cell lung cancer. Therefore, it is critical to determine whether advancements in overall survival with immunotherapy can be translated earlier into the treatment paradigm for LS-SCLC. Decades of robust preclinical research into the synergism of radiation therapy and immunotherapy set the stage for the combination of these treatment modalities. Recently published data suggests tolerability of single agent immunotherapy concurrent with chemoradiation in LS-SCLC, along with promising efficacy. However, combination immunotherapy in the consolidation setting appears too toxic, although this may be reflective of the dosing schedule rather than inherent to any combination immune checkpoint blockade. Here, we review underlying mechanisms of synergy with the combination of radiation and immunotherapy, the safety and efficacy of respective treatment modalities, and the ongoing trials that are exploring novel therapeutic approaches for LS-SCLC. Pivotal trials in LS-SCLC are ongoing and anticipated to aid in understanding efficacy and safety of immunotherapy with concurrent platinum-based chemoradiotherapy.
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Affiliation(s)
- Brian Schlick
- Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, 12902 Magnolia Dr, GME Office, Tampa, FL 33612 USA
| | - Misty Dawn Shields
- Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, 12902 Magnolia Dr, GME Office, Tampa, FL 33612 USA
| | - Julian A. Marin-Acevedo
- Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, 12902 Magnolia Dr, GME Office, Tampa, FL 33612 USA
| | - Ishika Patel
- Department of Public Health, University of South Florida, 4202 E Fowler Ave, Tampa, FL 33620 USA
| | - Bruna Pellini
- Department of Oncologic Sciences, Morsani College of Medicine, University of South Florida, 12902 Magnolia Dr, GME Office, Tampa, FL 33612 USA
- Department of Thoracic Oncology, Moffitt Cancer Center and Research Institute, 12902 Magnolia Dr, CSB 6-THOR PROG, Tampa, FL 33612 USA
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18
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Kapacee ZA, Allison J, Dawod M, Wang X, Frizziero M, Chakrabarty B, Manoharan P, McBain C, Mansoor W, Lamarca A, Hubner R, Valle JW, McNamara MG. The Management and Outcomes of Patients with Extra-Pulmonary Neuroendocrine Neoplasms and Brain Metastases. Curr Oncol 2022; 29:5110-5125. [PMID: 35877265 PMCID: PMC9319979 DOI: 10.3390/curroncol29070405] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2022] [Revised: 07/11/2022] [Accepted: 07/13/2022] [Indexed: 11/26/2022] Open
Abstract
Background: Brain metastases (BMs) in patients with extra-pulmonary neuroendocrine neoplasms (EP–NENs) are rare, and limited clinical information is available. The aim of this study was to detail the clinicopathological features, management and outcomes in patients with EP–NENs who developed BMs. Methods: A retrospective single-centre analysis of consecutive patients with EP–NENs (August 2004–February 2020) was conducted. Median overall survival (OS)/survival from BMs diagnosis was estimated (Kaplan–Meier). Results: Of 730 patients, 17 (1.9%) had BMs, median age 61 years (range 15–77); 8 (53%) male, unknown primary NEN site: 40%. Patients with BMs had grade 3 (G3) EP–NENs 11 (73%), G2: 3 (20%), G1: 1 (7%). Eight (53%) had poorly differentiated NENs, 6 were well-differentiated and 1 was not recorded. Additionally, 2 (13%) patients had synchronous BMs at diagnosis, whilst 13 (87%) developed BMs metachronously. The relative risk of developing BMs was 7.48 in patients with G3 disease vs. G1 + G2 disease (p = 0.0001). Median time to the development of BMs after NEN diagnosis: 15.9 months (range 2.5–139.5). Five patients had a solitary BM, 12 had multiple BMs. Treatment of BMs were surgery (n = 3); radiotherapy (n = 5); 4: whole brain radiotherapy, 1: conformal radiotherapy (orbit). Nine (53%) had best supportive care. Median OS from NEN diagnosis was 23.6 months [95% CI 15.2–31.3]; median time to death from BMs diagnosis was 3.0 months [95% CI 0.0–8.3]. Conclusion: BMs in patients with EP–NENs are rare and of increased risk in G3 vs. G1 + G2 EP–NENs. Survival outcomes are poor, and a greater understanding is needed to improve therapeutic outcomes.
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Affiliation(s)
- Zainul-Abedin Kapacee
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK; (Z.-A.K.); (J.A.); (M.D.); (W.M.); (A.L.); (R.H.); (J.W.V.)
| | - Jennifer Allison
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK; (Z.-A.K.); (J.A.); (M.D.); (W.M.); (A.L.); (R.H.); (J.W.V.)
| | - Mohammed Dawod
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK; (Z.-A.K.); (J.A.); (M.D.); (W.M.); (A.L.); (R.H.); (J.W.V.)
| | - Xin Wang
- Statistics Group, Digital Services, The Christie NHS Foundation Trust, Manchester M20 4BX, UK;
| | - Melissa Frizziero
- Cancer Research UK Manchester Institute, University of Manchester, Manchester M20 4BX, UK;
| | - Bipasha Chakrabarty
- Department of Pathology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK;
| | - Prakash Manoharan
- Department of Nuclear Medicine/Radiology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK;
| | - Catherine McBain
- Department of Clinical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK;
| | - Was Mansoor
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK; (Z.-A.K.); (J.A.); (M.D.); (W.M.); (A.L.); (R.H.); (J.W.V.)
| | - Angela Lamarca
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK; (Z.-A.K.); (J.A.); (M.D.); (W.M.); (A.L.); (R.H.); (J.W.V.)
| | - Richard Hubner
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK; (Z.-A.K.); (J.A.); (M.D.); (W.M.); (A.L.); (R.H.); (J.W.V.)
| | - Juan W. Valle
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK; (Z.-A.K.); (J.A.); (M.D.); (W.M.); (A.L.); (R.H.); (J.W.V.)
- Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, UK
| | - Mairéad G. McNamara
- Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester M20 4BX, UK; (Z.-A.K.); (J.A.); (M.D.); (W.M.); (A.L.); (R.H.); (J.W.V.)
- Division of Cancer Sciences, University of Manchester, Manchester M13 9PL, UK
- Correspondence:
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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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20
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Brenner AW, Patel AJ. Review of Current Principles of the Diagnosis and Management of Brain Metastases. Front Oncol 2022; 12:857622. [PMID: 35686091 PMCID: PMC9171239 DOI: 10.3389/fonc.2022.857622] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Accepted: 04/25/2022] [Indexed: 12/25/2022] Open
Abstract
Brain metastases are the most common intracranial tumors and are increasing in incidence as overall cancer survival improves. Diagnosis of brain metastases involves both clinical examination and magnetic resonance imaging. Treatment may involve a combination of surgery, radiotherapy, and systemic medical therapy depending on the patient's neurologic status, performance status, and overall oncologic burden. Advances in these domains have substantially impacted the management of brain metastases and improved performance status and survival for some patients. Indications for surgery have expanded with improved patient selection, imaging, and intraoperative monitoring. Robust evidence supports the use of whole brain radiotherapy and stereotactic radiosurgery, for both standalone and adjuvant indications, in almost all patients. Lastly, while systemic medical therapy has historically provided little benefit, modern immunotherapeutic agents have demonstrated promise. Current investigation seeks to determine the utility of neoadjuvant radiotherapy and laser interstitial thermal therapy, which have shown benefit in limited studies to date. This article provides a review of the epidemiology, pathology, diagnosis, and treatment of brain metastases and the corresponding supporting evidence.
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Affiliation(s)
| | - Akash J. Patel
- Department of Neurosurgery, Baylor College of Medicine, Houston, TX, United States
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21
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Chen MY, Ji Y, Hu X, Chen M. Factors Affecting the Risk of Brain Metastasis in Limited-Stage Small Cell Lung Cancer After Prophylactic Cranial Irradiation. Cancer Manag Res 2022; 14:1807-1814. [PMID: 35634538 PMCID: PMC9138691 DOI: 10.2147/cmar.s347449] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2021] [Accepted: 04/11/2022] [Indexed: 11/29/2022] Open
Abstract
Background Prophylactic cranial irradiation (PCI) can reduce the risk of brain metastases (BM) and improve overall survival (OS) in patients with limited-stage small cell lung cancer (LS-SCLC) after partial or complete response to primary therapy. However, some SCLC patients still develop BM after PCI. This study aimed to evaluate the risk factors of BM in patients with LS-SCLC after PCI and identify characteristics of patients who may not benefit from PCI. Methods and Materials We identified 550 patients with LS-SCLC who received chemoradiotherapy at Zhejiang Cancer Hospital between 2002 and 2017. All patients received PCI. Kaplan–Meier analyses and Cox regression analyses were used to identify factors affecting OS and brain metastasis-free survival (BMFS). Results For this patient population, the median survival time was 27.9 months, and the 5-year OS rate was 31%. The median survival time was 24.9 months (95% CI: 22.6–27.2 months), and 30.2 months (95% CI: 24.2–36.3 months) in patients with or without BM (P = 0.000). The overall BM rate was 15.6% (86/550). The frequency of BM in patients with pathologic stages I, II, and III were 9.3% (4/43), 13.4% (7/52), and 16.5% (75/455). The patients with tumors ≥5 cm had an increased risk of BM (HR: 1.781, 95% CI: 1.044–3.039, P = 0.034) but not death (HR: 1.126, 95% CI: 0.925–1.663, P = 0.182). The median survival time among patients <60 years was significantly longer than patients ≥60 years (34.9 months vs 24.6 months, P = 0.001); however, the difference in the BM risk between the two groups was not statistically significant. Conclusion PCI remains the standard of care for LS-SCLC patients who achieve complete or partial response after completion of chemoradiotherapy. However, patients with tumors ≥5 cm may have a higher risk of developing BM after PCI.
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Affiliation(s)
- Meng-Yuan Chen
- Department of Radiation Oncology, Institute of Cancer and Basic Medicine of Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, People’s Republic of China
| | - Yongling Ji
- Department of Radiation Oncology, Institute of Cancer and Basic Medicine of Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, People’s Republic of China
| | - Xiao Hu
- Department of Radiation Oncology, Institute of Cancer and Basic Medicine of Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, People’s Republic of China
| | - Ming Chen
- Department of Radiation Oncology, Institute of Cancer and Basic Medicine of Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, 310022, People’s Republic of China
- Correspondence: Ming Chen, Department of Radiation Oncology, Institute of Cancer and Basic Medicine of Chinese Academy of Sciences, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, No. 1, East Banshan Road, Banshan District, Hangzhou, 310022, People’s Republic of China, Email
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22
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Mathis NJ, Wijetunga NA, Imber BS, Pike LRG, Yang JT. Recent Advances and Applications of Radiation Therapy for Brain Metastases. Curr Oncol Rep 2022; 24:335-342. [PMID: 35133614 DOI: 10.1007/s11912-022-01209-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/12/2021] [Indexed: 12/25/2022]
Abstract
PURPOSE OF REVIEW Radiation therapy (RT) is a mainstay of treatment for brain metastases from solid tumors. Treatment of these patients is complex and should focus on minimizing symptoms, preserving functional status, and prolonging survival. RECENT FINDINGS Whole-brain radiotherapy (WBRT) can lead to toxicity, and while it does reduce recurrence in the CNS, this has not been shown to provide a survival benefit. Recent advances focus on reducing the toxicity of WBRT or using more targeted radiation therapy. New paradigms including the use of proton RT for leptomeningeal metastases (LM) and stereotactic radiosurgery (SRS) before craniotomy hold promise in improving treatment efficacy and reducing toxicity. Omission or replacement of WBRT is often safe and the use of SRS is expanding to include patients with more lesions and preoperative RT. Proton RT holds promise for LM. Progress is being made in improving patient-centered outcomes and reducing toxicity for patients with brain metastases.
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Affiliation(s)
- Noah J Mathis
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA
| | - N Ari Wijetunga
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA
| | - Brandon S Imber
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA
| | - Luke R G Pike
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA
| | - Jonathan T Yang
- Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.
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23
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Lim YJ, Song C, Kim HJ. Survival impact of prophylactic cranial irradiation in small-cell lung cancer in the modern era of magnetic resonance imaging staging. Radiat Oncol 2022; 17:26. [PMID: 35123531 PMCID: PMC8817587 DOI: 10.1186/s13014-022-01994-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 01/19/2022] [Indexed: 01/12/2023] Open
Abstract
Background In the modern era of magnetic resonance imaging (MRI) staging, the benefit of prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC) has been controversial. This study evaluated the prognostic impact of PCI in patients with limited- or extensive-stage SCLC who had no brain metastases at diagnosis according to MRI. Methods Data from newly diagnosed patients in 2014 from the Korean Association for Lung Cancer Registry database were used. Patients with limited- or extensive-stage SCLC who had no brain metastases according to MRI were identified. Univariate and multivariate survival analyses were conducted to assess the prognostic association of PCI. Results Of 107 and 122 patients with limited- and extensive-stage SCLC, 24% and 14% received PCI, respectively. In the limited-stage SCLC group, the 2-year overall survival (OS) rates of patients who received PCI and those who did not were 50% and 29% (P = 0.018), respectively. However, there was no significant difference in OS for patients with extensive-stage SCLC (P = 0.336). After adjusting for other covariates, PCI was found to be associated with improved OS in the limited-stage SCLC group (P = 0.005). Based on the time-course hazard rate function plots in the limited-stage SCLC group, the OS benefit of PCI was maximized within the first year of follow-up. Conclusions In the modern era of MRI staging, PCI might be beneficial for patients with limited-stage SCLC but not for those with extensive-stage SCLC. Further studies with a large sample size are needed to verify the prognostic association of PCI. Supplementary Information The online version contains supplementary material available at 10.1186/s13014-022-01994-8.
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24
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Yu NY, Sio TT, Ernani V, Savvides P, Schild SE. Role of Prophylactic Cranial Irradiation in Extensive-Stage Small Cell Lung Cancer. J Natl Compr Canc Netw 2021; 19:1465-1469. [PMID: 34902829 DOI: 10.6004/jnccn.2021.7105] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Accepted: 10/21/2021] [Indexed: 11/17/2022]
Abstract
Patients with small cell lung cancer (SCLC) are at significant risk of developing brain metastases during their disease course. Prophylactic cranial irradiation (PCI) has been incorporated into SCLC treatment guidelines to diminish the risk of developing brain metastases. In 2007, a randomized trial suggested that PCI decreases the incidence of brain metastases and prolongs overall survival (OS) in patients with extensive-stage SCLC (ES-SCLC) who have responded to initial therapy. However, this study did not include modern central nervous system imaging with CT or MRI prior to randomization. A more recent Japanese trial with MRI staging and surveillance demonstrated that PCI diminished the incidence of brain metastases but did not improve survival. This review examines the largest clinical studies, controversies, and future directions of PCI in patients with ES-SCLC.
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Affiliation(s)
| | | | - Vinicius Ernani
- Division of Hematology and Medical Oncology, Mayo Clinic Hospital, Phoenix, Arizona
| | - Panayiotis Savvides
- Division of Hematology and Medical Oncology, Mayo Clinic Hospital, Phoenix, Arizona
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25
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Crockett C, Belderbos J, Levy A, McDonald F, Le Péchoux C, Faivre-Finn C. Prophylactic cranial irradiation (PCI), hippocampal avoidance (HA) whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) in small cell lung cancer (SCLC): Where do we stand? Lung Cancer 2021; 162:96-105. [PMID: 34768007 DOI: 10.1016/j.lungcan.2021.10.016] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2021] [Accepted: 10/31/2021] [Indexed: 12/25/2022]
Abstract
Small cell lung cancer (SCLC) is an aggressive form of lung cancer associated with an increased risk of develping brain metastases (BM), which are a significant cause of morbidity and mortality. Prophylactic cranial irradiation (PCI) was first introduced in the 1970s with the aim of reducing BM incidence and improving survival and quality of life (QoL). Prospective clinical trials and meta-analyses have demonstrated its effectiveness in reducing BM incidence and improving survival, across all stages of the disease following response to induction chemotherapy. Despite its long history, "unknowns" surrounding PCI use still exist and there are particular subgroups of patients for which its use remains controversial. PCI is known to cause neurocognitive toxicity which can have a significant impact on a patient's QoL. Strategies to minimise this, including the use of hippocampal avoidance radiotherapy techniques, neuroprotective drugs and stereotactic radiosurgery in place of whole brain radiotherapy for the treatment of BM, are under evaluation. This review offers a summary of the key PCI trials published to date and the current treatment recommendations based on available evidence. It also discusses the key questions being addressed in ongoing clinical trials and highlights others where there is currently a knowledge gap and therefore where further data are urgently required.
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Affiliation(s)
- Cathryn Crockett
- Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, United Kingdom.
| | - José Belderbos
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, the Netherlands
| | - Antonin Levy
- Department of Radiation Oncology, International Center for Thoracic Cancers (CICT), Gustave Roussy, F-94805 Villejuif, France; Université Paris-Saclay, Faculté de Médecine, 94270 Le Kremlin-Bicêtre, France
| | - Fiona McDonald
- Department of Radiotherapy, Royal Marsden NHS Foundation Trust, London, United Kingdom
| | - Cecile Le Péchoux
- Department of Radiation Oncology, International Center for Thoracic Cancers (CICT), Gustave Roussy, F-94805 Villejuif, France
| | - Corinne Faivre-Finn
- Radiotherapy Related Research, The Christie NHS Foundation Trust, Manchester, United Kingdom; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, United Kingdom
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26
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Tariq S, Kim SY, Monteiro de Oliveira Novaes J, Cheng H. Update 2021: Management of Small Cell Lung Cancer. Lung 2021; 199:579-587. [PMID: 34757446 DOI: 10.1007/s00408-021-00486-y] [Citation(s) in RCA: 49] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Accepted: 10/16/2021] [Indexed: 12/27/2022]
Abstract
BACKGROUND Accounting for 14% of lung cancer, small cell lung cancer (SCLC) is a highly aggressive neuroendocrine malignancy with rapid proliferation, early spread, and poor survival. AIM AND METHODS We provide an overview of recent advances regarding SCLC pathogenesis, subtypes, and treatment development through literature review of key trials. RESULTS There are no validated biomarkers or approved targeted treatments for this overly heterogeneous disease, but recent analyses have identified some promising targets and four major subtypes which may carry unique therapeutic vulnerabilities in SCLC. Treatment wise, only a third of patients present with limited stage SCLC, which can be managed with a combined modality approach with curative intent (usually chemo-radiotherapy, but in some eligible patients, surgery followed by systemic treatment). For advanced or extensive stage SCLC, combined chemotherapy (platinum-etoposide) and immunotherapy (atezolizumab or durvalumab during and after chemotherapy) has become the new standard front-line treatment, with modest improvement in overall survival. In the second-line setting, for disease relapse ≤ 6 months, topotecan, lurbinectedin, and clinical trials are reasonable treatment options; for disease relapse > 6 months, original regimen, topotecan or lurbinectedin can be considered. Moreover, Trilaciclib, a CD4/CD6 inhibitor, was recently FDA-approved to decrease the incidence of chemotherapy-related myelosuppression in SCLC patients. CONCLUSIONS While modest improvements in survival have been made especially in the metastatic setting with chemo-immunotherapy, further research in understanding the biology of SCLC is warranted to develop biomarker-driven therapeutic strategies and combinational approaches for this aggressive disease.
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Affiliation(s)
- Sara Tariq
- Department of Medical Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, 10461, USA
| | - So Yeon Kim
- Department of Medical Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, 10461, USA
| | | | - Haiying Cheng
- Department of Medical Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
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Raghavapudi H, Singroul P, Kohila V. Brain Tumor Causes, Symptoms, Diagnosis and Radiotherapy Treatment. Curr Med Imaging 2021; 17:931-942. [PMID: 33573575 DOI: 10.2174/1573405617666210126160206] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2020] [Revised: 12/15/2020] [Accepted: 12/17/2020] [Indexed: 11/22/2022]
Abstract
The strategy used for the treatment of given brain cancer is critical in determining the post effects and survival. An oncological diagnosis of tumor evaluates a range of parameters such as shape, size, volume, location and neurological complexity that define the symptomatic severity. The evaluation determines a suitable treatment approach chosen from a range of options such as surgery, chemotherapy, hormone therapy, radiation therapy and other targeted therapies. Often, a combination of such therapies is applied to achieve superior results. Radiotherapy serves as a better treatment strategy because of a higher survival rate. It offers the flexibility of synergy with other treatment strategies and fewer side effects on organs at risk. This review presents a radiobiological perspective in the treatment of brain tumor. The cause, symptoms, diagnosis, treatment, post-treatment effects and the framework involved in its elimination are summarized.
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Affiliation(s)
- Haarika Raghavapudi
- Department of Biotechnology, National Institute of Technology Warangal, Warangal -506004, Telangana, India
| | - Pankaj Singroul
- Department of Biotechnology, National Institute of Technology Warangal, Warangal -506004, Telangana, India
| | - V Kohila
- Department of Biotechnology, National Institute of Technology Warangal, Warangal -506004, Telangana, India
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28
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Li J, Ding C, Yang C, Wang S, Qiao X. Prophylactic cranial irradiation confers favourable prognosis for patients with limited-stage small cell lung cancer in the era of MRI: A propensity score-matched analysis. J Med Imaging Radiat Oncol 2021; 65:778-785. [PMID: 34159731 DOI: 10.1111/1754-9485.13269] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2020] [Accepted: 06/01/2021] [Indexed: 11/28/2022]
Abstract
INTRODUCTION Prophylactic cranial irradiation (PCI) is recommended for patients with limited-stage small cell lung cancer (LS-SCLC) who achieve good response after chemoradiotherapy. But PCI is neurotoxic. Magnetic resonance imaging (MRI) is the standard tool for evaluating brain metastasis (BM). This study was to retrospectively analyse the necessity of PCI in the era of MRI in LS-SCLC. METHODS From July 2013 to June 2017, 190 patients with LS-SCLC who were treated with definitive chemoradiotherapy were included and analysed in this study. They were divided into the PCI group and non-PCI group. Propensity score matching (PSM) analysis was used to balance the variable differences. The Kaplan-Meier method was applied to estimate survival with log-rank test to ascertain significance between different groups. RESULTS Seventy-seven patients (40.5%) received PCI after chemoradiotherapy. After adjustment for propensity scores, 69 pairs of patients were matched between two groups. After PSM, the 1-year and 3-year OS rates were 96.9% and 48.5% in PCI group versus 89.9% and 25.0% in non-PCI group (HR: 0.419, 95% CI: 0.251-0.701, P = 0.001). The 1-year and 3-year BMFS in PCI group were 96.8% and 67.5% versus 62.3% and 37.9% in non-PCI group (HR: 0.247, 95% CI: 0.132-0.460, P < 0.001). CONCLUSION For patients showing no BM on MRI after definitive CRT, PCI confers less BM and better OS in LS-SCLC.
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Affiliation(s)
- Jing Li
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Cuimin Ding
- Department of Respiratory Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Chen Yang
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Shuoshuo Wang
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Xueying Qiao
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
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Johal S, Hettle R, Carroll J, Maguire P, Wynne T. Real-world treatment patterns and outcomes in small-cell lung cancer: a systematic literature review. J Thorac Dis 2021; 13:3692-3707. [PMID: 34277061 PMCID: PMC8264706 DOI: 10.21037/jtd-20-3034] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Accepted: 03/25/2021] [Indexed: 01/22/2023]
Abstract
Background Small-cell lung cancer (SCLC) accounts for 12-15% of lung cancers and is associated with poor survival outcomes and high symptom burden. This study employed a broad, systematic search strategy and timeframe to identify evidence on real-world treatment patterns and outcomes for SCLC outside the USA, including understanding sub-populations such as extensive-stage (ES) or limited-stage (LS) disease. Methods Databases (MEDLINE, Embase, and EBM reviews) were searched for journal articles published in the English language between 1 January 2000-1 March 2020 and supplemented by hand searching of conference abstracts and posters presented at conferences between 1 January 2016-1 March 2020 reporting real-world treatment outcomes in patients with SCLC. A targeted clinical guideline review was also completed. Results One-hundred studies provided quantitative data; 57 were available as full-text articles, whilst the remaining 43 were presented as abstracts or posters. The majority (80 studies, 80%) of included studies reported treatment in the first-line setting, where platinum-based chemotherapy and chemoradiotherapy was the most commonly used treatment strategy, in line with current treatment guidelines in SCLC. First-line treatments were found to have a high response rate; however, most patients relapsed early. No studies reported treatment or outcomes with immune-oncology therapies. Second-line treatment options were very limited, and primarily consisted of either re-treatment with first-line regimen or topotecan, but the prognosis for these patients remained poor. Outcomes were particularly poor amongst those with ES or relapsed disease vs. LS disease. Conclusions SCLC treatment patterns and short survival outcomes have remained constant over the previous 20 years. Due to the search timeframe, none of the studies identified reported on the impact of recently approved immune-oncology therapies in SCLC. Further data is needed on the impact of immunotherapies on treatment patterns and real-world outcomes in SCLC.
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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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Ghanta S, Keller A, Rodríguez-López JL, Patel A, Beriwal S. Utility of Prophylactic Cranial Irradiation for Limited Stage Small Cell Lung Cancer in the Modern Era with Magnetic Resonance Imaging Surveillance. Clin Oncol (R Coll Radiol) 2021; 33:e323-e330. [PMID: 33888381 DOI: 10.1016/j.clon.2021.03.018] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 03/03/2021] [Accepted: 03/23/2021] [Indexed: 02/07/2023]
Abstract
AIMS To retrospectively analyse the impact of prophylactic cranial irradiation (PCI) on survival and intracranial progression in patients with limited stage small cell lung cancer (LS-SCLC) in the modern era of widespread magnetic resonance imaging brain screening. MATERIALS AND METHODS Patients with LS-SCLC treated within our network between 2009 and 2020 who responded to initial therapy were stratified by receipt of PCI and stage of disease. A propensity score match analysis was carried out for stage II-III patients. Overall and neurological survival were defined as time to death and presumed death due to uncontrolled intracranial disease, respectively. Brain metastasis-free survival and symptomatic brain metastasis-free survival were defined as freedom from intracranial progression and symptomatic intracranial progression, respectively. The effect of PCI on these outcomes was assessed using Kaplan-Meier and Cox proportional hazards models. RESULTS In total, 243 (69.6%) of 349 patients received PCI. On multivariate analysis in the propensity matched stage II-III cohort, PCI was a significant predictor of improved neurological survival (hazard ratio 0.23, 95% confidence interval 0.08-0.65; P = 0.01), brain metastasis-free survival (hazard ratio 0.25, 95% confidence interval 0.12-0.51; P < 0.01) and symptomatic brain metastasis-free survival (hazard ratio 0.21, 95% confidence interval 0.08-0.55; P < 0.01), but not improved overall survival. Two-year neurological survival estimates within the propensity matched cohort were 96.8% (95% confidence interval 87.6-99.2%) with PCI and 77.2% (95% confidence interval 63.0-86.4%) without PCI and 1- and 2-year estimates of incidence of brain metastases were 3.9% (95% confidence interval 1.3-11.7%) and 11.7% (95% confidence interval 5.6-23.5%) in the PCI group and 31.6% (95% confidence interval 22.1-43.9%) and 40.4% (95% confidence interval 29.2-54.0%) in the no PCI group, respectively. CONCLUSIONS In the modern era of magnetic resonance imaging screening, PCI was associated with reduced incidence of intracranial progression in patients with stage II-III LS-SCLC who respond to initial therapy. This, importantly, translated to a decreased risk of neurological death within our propensity matched cohort, without significant improvement in overall survival.
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Affiliation(s)
- S Ghanta
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - A Keller
- Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA
| | - J L Rodríguez-López
- Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA
| | - A Patel
- Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA
| | - S Beriwal
- Department of Radiation Oncology, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA.
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Cho Y, Lee J, Lee IJ, Kim JW, Baek JG, Jung DM, Cho BC, Hong MH, Kim HR, Lee CG, Yoon HI. Intracranial failure after hippocampal-avoidance prophylactic cranial irradiation in limited-stage small-cell lung cancer patients. Sci Rep 2021; 11:7435. [PMID: 33795826 PMCID: PMC8016941 DOI: 10.1038/s41598-021-86851-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2020] [Accepted: 03/22/2021] [Indexed: 11/20/2022] Open
Abstract
We evaluated intracranial failure after hippocampus-avoidance-prophylactic cranial irradiation (HA-PCI) for limited-stage small-cell lung cancer (SCLC). Data of 106 patients who received PCI with 25 Gy were retrospectively reviewed. The patients were divided into two groups based on whether they underwent HA-PCI: the HA-PCI group (n = 48) and the conventional PCI (C-PCI) group (n = 58). Twenty-one patients experienced intracranial failure: 11 and 10 patients in the C-PCI and HA-PCI groups, respectively. Using the log-rank test, the intracranial failure rate was not significantly different between the groups (p = 0.215). No clinical factor was significantly associated with intracranial failure in multivariate Cox regression analysis, but HA-PCI tended to be associated with increased incidence of intracranial failure (HR 2.87, 95% CI 0.86–9.58, p = 0.087). Among patients who received HA-PCI, two developed peri-hippocampal recurrence. A higher thoracic radiotherapy dose (≥ 60 Gy) was significantly associated with DFS (HR 0.52, p = 0.048) and OS (HR 0.35, p = 0.003). However, HA-PCI was associated with neither DFS nor OS. Although HA-PCI may be associated with an increased risk of intracranial failure, HA-PCI did not impair disease control or survival. Future prospective randomized trials are needed to reach a definite conclusion.
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Affiliation(s)
- Yeona Cho
- Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Joongyo Lee
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Ik Jae Lee
- Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jun Won Kim
- Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jong Geol Baek
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Dong Min Jung
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Byoung Chul Cho
- Department of Internal Medicine, Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Min Hee Hong
- Department of Internal Medicine, Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hye Ryun Kim
- Department of Internal Medicine, Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chang Geol Lee
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea
| | - Hong In Yoon
- Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, 03722, Republic of Korea.
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Utility of Prophylactic Cranial Irradiation for Extensive-Stage Small-Cell Lung Cancer in the MRI Screening Era. Clin Lung Cancer 2021; 22:e808-e816. [PMID: 33966983 DOI: 10.1016/j.cllc.2021.03.009] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2020] [Revised: 03/03/2021] [Accepted: 03/18/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND Conflicting data exists regarding the benefit of prophylactic cranial irradiation (PCI) in patients with extensive-stage small-cell lung cancer (ES-SCLC). We sought to retrospectively review outcomes of patients within our network with ES-SCLC treated with and without PCI between 2009 and 2020. METHODS Endpoints assessed using the Kaplan-Meier estimator were overall survival (OS), freedom from death with uncontrolled intracranial disease (UI-DFS), brain metastasis-free survival (BMFS), and symptomatic BMFS (SBMFS). Log-rank test was performed for univariate comparison of outcomes, with Cox regression performed for univariate and multivariable analysis of OS and UI-DFS. RESULTS Some 250 patients were determined to be eligible for PCI based on any response to upfront chemotherapy, with 46 patients excluded owing to lack of negative staging brain magnetic resonance imaging (MRI). Brain MRI was performed both at diagnosis and near completion of chemotherapy in 108 patients, with brain metastases identified near completion of chemotherapy in 17 patients (15.7%), excluding them from further analysis. Median OS in remaining eligible 187 patients was 9.0 months, with 2-year Kaplan-Meier estimate of OS of 21.9%. PCI was associated with improved UI-DFS, BMFS, and SBMFS. However, PCI was not associated with improved OS in the entire cohort or the propensity matched cohort. CONCLUSION Our study suggests screening with MRI following chemotherapy is important because of the identification of unsuspected brain metastases in nearly 16% of patients with response to chemotherapy. PCI is associated with reduction in brain metastases, without a demonstrable impact on OS in the era of MRI screening.
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Stroke-Like Migraine Attacks After Radiation Therapy (SMART) Syndrome: A Comprehensive Review. Curr Pain Headache Rep 2021; 25:33. [PMID: 33761013 DOI: 10.1007/s11916-021-00946-3] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/12/2021] [Indexed: 10/21/2022]
Abstract
PURPOSE OF REVIEW SMART syndrome is a delayed complication of cranial irradiation that can be misconstrued as tumor recurrence or some other intracranial neurological disease. Recognition of this clinical syndrome is imperative as it can obviate the need for invasive diagnostic testing and can provide reassurance to both the patient and their loved ones. RECENT FINDINGS SMART syndrome is generally considered a reversible clinical syndrome; however, neurological deficits may become permanent. Pathophysiology of SMART syndrome may involve cerebrovascular autoregulation impairment, neuronal dysfunction leading to trigeminovascular system impairment and/or cortical spreading depression, and seizures. In addition to MRI brain with gadolinium, other imaging modalities, such as CT perfusion, MR perfusion, MR spectroscopy, and FDG PET/CT, aid in arriving to the diagnosis sooner. Patients should also undergo electroencephalogram in order to promptly identify and treat seizures. There are currently no clear guidelines on how to effectively treat SMART syndrome, but treatment may involve anti-seizure medication, anti-hypertensives, anti-platelet, and steroid therapy. This review provides a comprehensive understanding of the clinical characteristics of SMART syndrome from presentation to diagnostic evaluation. We also discuss radiographic features and treatment strategies for this rare disease. With increased radiotherapy utilization, prompt clinical recognition of SMART syndrome and further development of a comprehensive diagnostic approach to SMART syndrome utilizing newer radiographic modalities as well as treatment algorithms to effectively treat this clinical condition will be imperative.
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Fievet L, Sculier JP, Meert AP, Berghmans T. [The role of prophylactic cranial irradiation in small cell lung cancer]. Rev Mal Respir 2021; 38:137-146. [PMID: 33546929 DOI: 10.1016/j.rmr.2021.01.003] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Accepted: 10/21/2020] [Indexed: 11/26/2022]
Abstract
INTRODUCTION Prophylactic cranial irradiation (PCI) is considered standard therapeutic management in small cell lung cancer (SCLC). This is based on old randomised trials with methodological limitations, namely the absence of magnetic resonance imaging (MRI) of the brain. The aim of this study is to assess the risk not administering PCI when systematic brain imaging is applied. METHODS Retrospective study including untreated SCLC, without PCI and receiving brain imaging at the time of diagnosis. Kaplan-Meier and log-rank statistics were used for survival analyses. RESULTS Among 150 patients, 75 were possibly eligible for PCI. Thirteen patients presented with an isolated brain recurrence as the first site of progression with no other metastatic sites apparent, and in 6 patients, the brain was the only recurrent site during the whole follow-up. In the group of patients eligible for PCI, there was no statistically significant survival difference according to the brain progression status (P=0.11). CONCLUSIONS The expected impact of PCI seems limited in terms of overall survival and prevention of isolated brain metastases in patients having systematic brain imaging during SCLC work-up.
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Affiliation(s)
- L Fievet
- Service des soins intensifs et urgences oncologiques, clinique d'oncologie thoracique, Institut Jules-Bordet, Université Libre de Bruxelles, Bruxelles, Belgique
| | - J-P Sculier
- Service des soins intensifs et urgences oncologiques, clinique d'oncologie thoracique, Institut Jules-Bordet, Université Libre de Bruxelles, Bruxelles, Belgique
| | - A-P Meert
- Service des soins intensifs et urgences oncologiques, clinique d'oncologie thoracique, Institut Jules-Bordet, Université Libre de Bruxelles, Bruxelles, Belgique
| | - T Berghmans
- Service des soins intensifs et urgences oncologiques, clinique d'oncologie thoracique, Institut Jules-Bordet, Université Libre de Bruxelles, Bruxelles, Belgique.
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Taylor JM, Rusthoven CG, Moghanaki D. Prophylactic cranial irradiation or MRI surveillance for extensive stage small cell lung cancer. J Thorac Dis 2020; 12:6225-6233. [PMID: 33209461 PMCID: PMC7656401 DOI: 10.21037/jtd.2020.03.80] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
The treatment paradigm for extensive stage small cell lung cancer (ES-SCLC) is evolving. Prophylactic cranial irradiation (PCI) has long been considered a component of standard treatment in patients with extensive stage disease who respond to chemotherapy. However, in the modern era of magnetic resonance imaging, the role of PCI has become an area of controversy following conflicting level I evidence. Due to conflicting data and toxicity concerns, the routine use of PCI has declined. Recent improvements in systemic disease control with the use of immunotherapy and reductions in the toxicity attributable to PCI with hippocampal avoidance and memantine have reignited the discussion. As such, we present here a narrative review of PCI with a focus on historical milestones, randomized data, risk mitigation and future directions.
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Affiliation(s)
- James M Taylor
- Department of Radiation Oncology, Sidney Kimmel Medical College & Cancer Center at Thomas Jefferson University, Philadelphia, PA, USA
| | - Chad G Rusthoven
- Department of Radiation Oncology, University of Colorado-Denver, Aurora, CO, USA
| | - Drew Moghanaki
- Department of Radiation Oncology, Atlanta VA Health Care System, Emory University School of Medicine, Atlanta, GA, USA
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Sawyer DM, Sawyer TW, Eshghi N, Hsu C, Hamilton RJ, Garland LL, Kuo PH. Pilot Study: Texture Analysis of PET Imaging Demonstrates Changes in 18F-FDG Uptake of the Brain After Prophylactic Cranial Irradiation. J Nucl Med Technol 2020; 49:34-38. [PMID: 33020232 DOI: 10.2967/jnmt.120.248393] [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: 04/28/2020] [Accepted: 08/07/2020] [Indexed: 11/16/2022] Open
Abstract
Prophylactic cranial irradiation (PCI) is used to decrease the probability of developing brain metastases in patients with small cell lung cancer and has been linked to deleterious cognitive effects. Although no well-established imaging markers for these effects exist, previous studies have shown that structural and metabolic changes in the brain can be detected with MRI and PET. This study used an image processing technique called texture analysis to explore whether global changes in brain glucose metabolism could be characterized in PET images. Methods: 18F-FDG PET images of the brain from patients with small cell lung cancer, obtained before and after the administration of PCI, were processed using texture analysis. Texture features were compared between the pre- and post-PCI images. Results: Multiple texture features demonstrated statistically significant differences before and after PCI when texture analysis was applied to the brain parenchyma as a whole. Regional differences were also seen but were not statistically significant. Conclusion: Global changes in brain glucose metabolism occur after PCI and are detectable using advanced image processing techniques. These changes may reflect radiation-induced damage and thus may provide a novel method for studying radiation-induced cognitive impairment.
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Affiliation(s)
- David M Sawyer
- Department of Medical Imaging, University of Arizona, Tucson, Arizona
| | - Travis W Sawyer
- College of Optical Sciences, University of Arizona, Tucson, Arizona
| | | | - Charles Hsu
- Department of Radiation Oncology, University of Arizona, Tucson, Arizona
| | - Russell J Hamilton
- Department of Radiation Oncology, University of Arizona, Tucson, Arizona
| | - Linda L Garland
- Department of Medicine, University of Arizona; University of Arizona Cancer Center, Tucson, Arizona; and
| | - Phillip H Kuo
- Department of Medical Imaging, University of Arizona, Tucson, Arizona.,Department of Medicine, University of Arizona; University of Arizona Cancer Center, Tucson, Arizona; and.,Department of Biomedical Engineering, University of Arizona, Tucson, Arizona
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Higgins KA, Simone CB, Amini A, Chetty IJ, Donington J, Edelman MJ, Chun SG, Kestin LL, Movsas B, Rodrigues GB, Rosenzweig KE, Slotman BJ, Rybkin II, Wolf A, Chang JY. American Radium Society Appropriate Use Criteria on Radiation Therapy for Extensive-Stage SCLC. J Thorac Oncol 2020; 16:54-65. [PMID: 33011389 DOI: 10.1016/j.jtho.2020.09.013] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 08/18/2020] [Accepted: 09/14/2020] [Indexed: 01/13/2023]
Abstract
INTRODUCTION The standard-of-care therapy for extensive-stage SCLC has recently changed with the results of two large randomized trials revealing improved survival with the addition of immunotherapy to first-line platinum or etoposide chemotherapy. This has led to a lack of clarity around the role of consolidative thoracic radiation and prophylactic cranial irradiation in the setting of chemoimmunotherapy. METHODS The American Radium Society Appropriate Use Criteria are evidence-based guidelines for specific clinical conditions that are reviewed by a multidisciplinary expert panel. The guidelines include a review and analysis of current evidence with the application of consensus methodology (modified Delphi) to rate the appropriateness of treatments recommended by the panel for extensive-stage SCLC. RESULTS Current evidence supports either prophylactic cranial irradiation or surveillance with magnetic resonance imaging every 3 months for patients without evidence of brain metastases. Patients with brain metastases should receive whole-brain radiation with a recommended dose of 30 Gy in 10 fractions. Consolidative thoracic radiation can be considered in selected cases with the recommended dose ranging from 30 to 54 Gy; this recommendation was driven by expert opinion owing to the limited strength of evidence, as clinical trials addressing this question remain ongoing. CONCLUSIONS Radiation therapy remains an integral component in the treatment paradigm for ES-SCLC.
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Affiliation(s)
| | - Kristin A Higgins
- Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, Georgia.
| | | | - Arya Amini
- Department of Radiation Oncology, City of Hope Comprehensive Cancer Center, Duarte, California
| | - Indrin J Chetty
- Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan
| | - Jessica Donington
- Department of Thoracic Surgery, The University of Chicago, Chicago, Illinois
| | - Martin J Edelman
- Department of Medical Oncology, Fox Chase Comprehensive Cancer Center, Philadelphia, Pennsylvania
| | - Stephen G Chun
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Larry L Kestin
- Department of Radiation Oncology, MHP Cancer Institute, Pontiac, Michigan
| | - Benjamin Movsas
- Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan
| | - George B Rodrigues
- Department of Radiation Oncology, London Health Sciences Centre, London, Ontario, Canada
| | - Kenneth E Rosenzweig
- Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York
| | - Ben J Slotman
- Department of Radiation Oncology, Amsterdam University Medical Centers, Amsterdam, The Netherlands
| | - Igor I Rybkin
- Department of Radiation Oncology, Henry Ford Health System, Detroit, Michigan; Department of Medical Oncology, Henry Ford Health System, Detroit, Michigan
| | - Andrea Wolf
- Department of Radiation Oncology, Mount Sinai School of Medicine, New York, New York
| | - Joe Y Chang
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas
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de Dios NR, Murcia-Mejía M. Current and future strategies in radiotherapy for small-cell lung cancer. J Clin Transl Res 2020; 6:97-108. [PMID: 33521370 PMCID: PMC7837740] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2020] [Revised: 06/12/2020] [Accepted: 07/17/2020] [Indexed: 11/24/2022] Open
Abstract
UNLABELLED Small-cell lung cancer (SCLC) accounts for 13% of all lung tumors. The standard treatment in patients with limited-stage (LS) disease is thoracic radiotherapy (TRT) combined with chemotherapy. In extensive-stage (ES) SCLC, the importance of consolidation TRT in patients with a good treatment response has become increasingly recognized. In both LS and ES disease, prophylactic cranial irradiation is recommended in patients who respond to treatment. New therapeutic approaches such as immunotherapy are being increasingly incorporated into the treatment of SCLC, although more slowly than in non-small cell lung cancer. Diverse radiation dose and fractionation schemes, administered in varying combinations with these new drugs, are being investigated. In the present article, we review and update the role of radiotherapy in the treatment of SCLC. We also discuss the main clinical trials currently underway to identify future trends. RELEVANCE FOR PATIENTS Radiotherapy is a critical component of multimodality treatment of SCLC. This article can help physicians to improve medical knowledge and find better ways to treat their SCLC patients.
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Affiliation(s)
- N. Rodríguez de Dios
- 1Department of Radiation Oncology, Hospital del Mar, Barcelona, Spain,2Hospital del Mar Medical Research Institute, Barcelona, Spain,3Pompeu Fabra University, Barcelona, Spain,
Corresponding author: Núria Rodríguez de Dios Department of Radiation Oncology, Hospital del Mar. Passeig Marítim, 25-29, 08003 Barcelona Tel.: 003493-367-4144
| | - M. Murcia-Mejía
- 4Department of Radiation Oncology, Hospital Sant Joan Reus, Tarragona
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Abi Jaoude J, Adib E, Kayali M, Khabsa J, Akl EA, Zeidan Y. Prophylactic cranial irradiation for patients with limited-stage small cell lung cancer. Hippokratia 2020. [DOI: 10.1002/14651858.cd013701] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
| | - Elio Adib
- Faculty of Medicine; American University of Beirut; Beirut Lebanon
| | - Majd Kayali
- Department of Radiation Oncology; American University of Beirut Medical Center; Beirut Lebanon
| | - Joanne Khabsa
- Clinical Research Institute; American University of Beirut Medical Center; Beirut Lebanon
| | - Elie A Akl
- Department of Internal Medicine; American University of Beirut Medical Center; Beirut Lebanon
| | - Youssef Zeidan
- Department of Radiation Oncology; American University of Beirut Medical Center; Beirut Lebanon
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Predictors of prognosis of synchronous brain metastases in small-cell lung cancer patients. Clin Exp Metastasis 2020; 37:531-539. [PMID: 32500410 DOI: 10.1007/s10585-020-10040-4] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2020] [Accepted: 05/29/2020] [Indexed: 10/24/2022]
Abstract
Patients with small cell lung cancer (SCLC) are more likely to have synchronous brain metastasis (SBM) at the time of diagnosis than patients with any other extracranial primary malignancy. We sought to identify which factors predicted an increased risk of SBM in SCLC as well as which factors affected the prognosis of these patients. 38,956 Patients in the Surveillance, Epidemiology, and End Results (SEER) database with microscopically confirmed SCLC from 2010 to 2016 were identified. 6264 (16.1%) Patients with SCLC had SBM at the time of diagnosis. In the multivariable logistic regression, disease specific factors that were predictive of SBM were primary tumor size > 7 cm (adjusted OR = 1.14, 95% CI [1.02, 1.28], p = 0.02), synchronous lung metastases, and synchronous bone metastases. Demographic specific factors predictive of increased SBM risk in this model were younger age, male sex, and race (American Indian/Alaska Native and black patients). Patients insured through Medicaid were less likely to present with SBM. In the multivariate Cox proportional hazards model, lack of insurance was the strongest predictor of mortality (adjusted HR = 1.47, 95% CI [1.26, 1.73], p < 0.001). Other factors associated with an increased risk of mortality include male sex, older age, health insurance coverage through Medicaid, synchronous liver metastasis, synchronous lung metastasis, and primary tumor size > 7 cm. In contrast, Asian patients had a lower risk of mortality. This study identifies risk factors for SBM among patients with SCLC, as well as indicators of prognosis among this patient population.
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Ding C, Li J, Wang S, Yang C, Zhang R, Bai W, Liu M, Zhen C, Qiao X. Prognostic factors for patients with limited-stage small-cell lung cancer without receiving prophylactic cranial irradiation. RADIATION MEDICINE AND PROTECTION 2020. [DOI: 10.1016/j.radmp.2020.05.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
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Zeng H, Hendriks LEL, van Geffen WH, Witlox WJA, Eekers DBP, De Ruysscher DKM. Risk factors for neurocognitive decline in lung cancer patients treated with prophylactic cranial irradiation: A systematic review. Cancer Treat Rev 2020; 88:102025. [PMID: 32512415 DOI: 10.1016/j.ctrv.2020.102025] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2020] [Revised: 04/21/2020] [Accepted: 04/28/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Prophylactic cranial irradiation (PCI) reduces brain metastasis incidence in lung cancer, however with risk of neurocognitive decline. Nevertheless, risk factors for neurocognitive decline after PCI remain unclear. METHODS We systematically reviewed the PubMed database according to the PRISMA guideline. Inclusion criteria were: randomized clinical trials (RCTs) and observational/single arm trials evaluating PCI, including ≥20 patients, reporting neurocognitive test results for lung cancer. Primary aim: evaluate risk factors associated with neurocognitive decline after PCI. RESULTS Twenty records were eligible (8 different RCTs, 8 observational studies), including 3553 patients in total (858 NSCLC, 2695 SCLC) of which 73.6% received PCI. Incidence of mild/moderate cognitive decline after PCI varied from 8 to 89% (grading not always provided); for those without PCI, this was 3.4-42%. Interestingly, 23-95% had baseline cognitive impairment. Risk factors were often not reported. In one trial, both age (>60 years) and higher PCI dose (36 Gy) including twice-daily PCI were associated with a higher risk of cognitive decline. In one trial, white matter abnormalities were more frequent in the concurrent or sandwiched PCI arm, but without significant neuropsychological differences. One trial identified hippocampal sparing PCI to limit the neurocognitive toxicities of PCI and another reported an association between hippocampal dose volume effects and memory decline. As neurocognition was a secondary endpoint in most RCTs, and was assessed by various instruments with often poor/moderate compliance, high-quality data is lacking. CONCLUSIONS Age, PCI dose, regimen and timing might be associated with cognitive impairment after PCI in lung cancer patients, but high-quality data is lacking. Future PCI trials should collect and evaluate possible risk factors systematically.
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Affiliation(s)
- Haiyan Zeng
- Department of Radiation Oncology (Maastro), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands.
| | - Lizza E L Hendriks
- Department of Pulmonary Diseases, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, the Netherlands.
| | - Wouter H van Geffen
- Department of Respiratory Medicine, Medical Centre Leeuwarden, Leeuwarden, the Netherlands.
| | - Willem J A Witlox
- Department of Clinical Epidemiology and Medical Technology Assessment, GROW - School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, the Netherlands.
| | - Danielle B P Eekers
- Department of Radiation Oncology (Maastro), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands.
| | - Dirk K M De Ruysscher
- Department of Radiation Oncology (Maastro), GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, The Netherlands.
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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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Abstract
PURPOSE OF REVIEW The current article reviews the state of art of prevention strategies for brain metastases from solid tumors and touches both old pivotal studies and new directions of personalized molecular approaches. RECENT FINDINGS Prophylactic cranial irradiation (PCI) has a definite role in the prevention of relapse into the brain for patients with small cell lung cancer (SCLC) responding to chemotherapy and radiotherapy as it prolongs overall survival (OS). However, the risk of late cognitive deficit following whole brain radiotherapy (WBRT) in this patient population is still not well known. Conversely, PCI significantly reduces the incidence of brain metastases and prolongs the disease-free interval in patients with non-SCLC (NSCLC), but does not improve OS thus far. Pharmacologic prevention is a new concept driven by the efficacy of targeted agents on macrometastases from specific molecular subgroups. SUMMARY The future challenges for prevention of brain metastases are represented by the identification of subgroups of patients at higher risk of relapse into the brain coupled with either new WBRT strategies to better preserve cognition or effective molecular agents to target micrometastases.
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Affiliation(s)
- Riccardo Soffietti
- Department of Neuro-Oncology, University and City of Health and Science Hospital, Turin, Italy
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Tendler S, Zhan Y, Pettersson A, Lewensohn R, Viktorsson K, Fang F, De Petris L. Treatment patterns and survival outcomes for small-cell lung cancer patients - a Swedish single center cohort study. Acta Oncol 2020; 59:388-394. [PMID: 31910696 DOI: 10.1080/0284186x.2019.1711165] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Objectives: This real-world study on small-cell lung cancer (SCLC) patients aimed to investigate treatment patterns, outcome of re-challenge with platinum doublet chemotherapy (PDCT), and associations between clinical characteristics and survival outcomes.Material and methods: This retrospective single center cohort study was based on patients diagnosed with SCLC between 2008 and 2016 at the Karolinska University Hospital, Stockholm, Sweden. Patients were divided into two subgroups; limited disease (LD), receiving concomitant chemo- and radiotherapy and extensive disease (ED), receiving palliative PDCT. The progression-free survival (PFS) was defined as the interval between the start of CT and the earliest date of documented progression. 'Refractory relapse' (Rr) and 'Sensitive relapse' (Sr) were defined as relapse occurring < or ≥180 days after start of PDCT, respectively. The results for treatment patterns were reported as numbers and percentages of patients, and descriptive analyses including medians and 95% confidence intervals (CIs). The Cox proportional hazards regression model was applied to assess the relationship between clinical characteristics and overall survival (OS).Results: The study included 544 patients; 408 with ED and 136 patients had LD. The median PFS and OS for ED patients were 5.1 and 7.0, respectively. In the ED subgroup, Sr occurred in 169 patients (41%), with a longer median OS when compared to Rr patients (10.8 vs. 3.6 months). Patients with LD had a median PFS and OS of 12 and 24 months, respectively. Some LD patients did not show a sign of relapse (22%). The majority of LD patients who relapsed had Sr (66%), with a longer median OS when compared to patients with Rr (20.9 vs. 7.8 mo).Conclusions: The survival outcomes for ED and LD SCLC patients correspond to historical data. Patients with Sr after 1st line therapy might benefit from re-challenge with PDCT in the 2nd line setting.
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Affiliation(s)
- Salomon Tendler
- Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
- Theme Cancer, Patient Area Head and Neck, Lung, and Skin Cancer, Karolinska University Hospital, Stockholm, Sweden
| | - Yiqiang Zhan
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Andreas Pettersson
- Department of Medicine Solna, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden
| | - Rolf Lewensohn
- Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
- Theme Cancer, Patient Area Head and Neck, Lung, and Skin Cancer, Karolinska University Hospital, Stockholm, Sweden
| | - Kristina Viktorsson
- Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
- Theme Cancer, Patient Area Head and Neck, Lung, and Skin Cancer, Karolinska University Hospital, Stockholm, Sweden
| | - Fang Fang
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
| | - Luigi De Petris
- Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden
- Theme Cancer, Patient Area Head and Neck, Lung, and Skin Cancer, Karolinska University Hospital, Stockholm, Sweden
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Schneider BJ, Ismaila N, Aerts J, Chiles C, Daly ME, Detterbeck FC, Hearn JWD, Katz SI, Leighl NB, Levy B, Meyers B, Murgu S, Nekhlyudov L, Santos ES, Singh N, Tashbar J, Yankelevitz D, Altorki N. Lung Cancer Surveillance After Definitive Curative-Intent Therapy: ASCO Guideline. J Clin Oncol 2020; 38:753-766. [PMID: 31829901 DOI: 10.1200/jco.19.02748] [Citation(s) in RCA: 115] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/18/2019] [Indexed: 11/20/2022] Open
Abstract
PURPOSE To provide evidence-based recommendations to practicing clinicians on radiographic imaging and biomarker surveillance strategies after definitive curative-intent therapy in patients with stage I-III non-small-cell lung cancer (NSCLC) and SCLC. METHODS ASCO convened an Expert Panel of medical oncology, thoracic surgery, radiation oncology, pulmonary, radiology, primary care, and advocacy experts to conduct a literature search, which included systematic reviews, meta-analyses, randomized controlled trials, and prospective and retrospective comparative observational studies published from 2000 through 2019. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations. RESULTS The literature search identified 14 relevant studies to inform the evidence base for this guideline. RECOMMENDATIONS Patients should undergo surveillance imaging for recurrence every 6 months for 2 years and then annually for detection of new primary lung cancers. Chest computed tomography imaging is the optimal imaging modality for surveillance. Fluorodeoxyglucose positron emission tomography/computed tomography imaging should not be used as a surveillance tool. Surveillance imaging may not be offered to patients who are clinically unsuitable for or unwilling to accept further treatment. Age should not preclude surveillance imaging. Circulating biomarkers should not be used as a surveillance strategy for detection of recurrence. Brain magnetic resonance imaging should not be used for routine surveillance in stage I-III NSCLC but may be used every 3 months for the first year and every 6 months for the second year in patients with stage I-III small-cell lung cancer who have undergone curative-intent treatment.
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Affiliation(s)
| | | | - Joachim Aerts
- Erasmus Medical Center Cancer Institute, Rotterdam, the Netherlands
| | | | - Megan E Daly
- University of California Davis Comprehensive Cancer Center, Sacramento, CA
| | | | | | - Sharyn I Katz
- University of Pennsylvania Perelman School of Medicine, Philadelphia, PA
| | - Natasha B Leighl
- Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Benjamin Levy
- Johns Hopkins Sidney Kimmel Cancer Center at Sibley Memorial Hospital, Washington, DC
| | | | | | | | | | - Navneet Singh
- Postgraduate Institute of Medical Education and Research, Chandigarh, India
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Sun A, Hu C, Wong SJ, Gore E, Videtic G, Dutta S, Suntharalingam M, Chen Y, Gaspar LE, Choy H. Prophylactic Cranial Irradiation vs Observation in Patients With Locally Advanced Non-Small Cell Lung Cancer: A Long-term Update of the NRG Oncology/RTOG 0214 Phase 3 Randomized Clinical Trial. JAMA Oncol 2020; 5:847-855. [PMID: 30869743 DOI: 10.1001/jamaoncol.2018.7220] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Importance Brain metastasis (BM) rates are high in locally advanced non-small cell lung cancer (LA-NSCLC), approaching rates seen in small cell lung cancer, where prophylactic cranial irradiation (PCI) is standard of care. Although PCI decreases the incidence of BM in LA-NSCLC, a survival advantage has not yet been shown. Objective To determine if PCI improves survival in LA-NSCLC. Design, Setting, and Participants Radiation Therapy Oncology Group (RTOG) 0214 was a randomized phase 3 clinical trial in stage III NSCLC stratified by stage (IIIA vs IIIB), histologic characteristics (nonsquamous vs squamous) and therapy (no surgery vs surgery). The study took place at 291 institutions in the United States, Canada, and internationally. Of 356 patients with stage III NSCLC entered onto this study, 16 were ineligible; therefore, 340 patients were randomized. Intervention for Clinical Trials Observation vs PCI. Main Outcomes and Measures The primary outcome was overall survival (OS). The secondary end points were disease-free survival (DFS) and incidence of BM. Results Of the 340 total participants, mean (SD) age was 61 years; 213 of the participants were men and 127 were women. The median follow-up time was 2.1 years for all patients, and 9.2 years for living patients. The OS for PCI was not significantly better than observation (hazard ratio [HR], 0.82; 95% CI, 0.63-1.06; P = .12; 5- and 10-year rates, 24.7% and 17.6% vs 26.0% and 13.3%, respectively), while the DFS (HR, 0.76; 95% CI, 0.59-0.97; P = .03; 5- and 10-year rates, 19.0% and 12.6% vs 16.1% and 7.5% for PCI vs observation) and BM (HR, 0.43; 95% CI, 0.24-0.77; P = .003; 5- and 10-year rates, 16.7% vs 28.3% for PCI vs observation) were significantly different. Patients in the PCI arm were 57% less likely to develop BM than those in the observation arm. Younger patients (<60 years) and patients with nonsquamous disease developed more BM. On multivariable analysis, PCI was associated with decreased BM and improved DFS, but not improved OS. Multivariable analysis within the nonsurgical arm suggests that PCI effectively prolongs OS, DFS, and BM. Conclusions and Relevance In patients with stage III LA-NSCLC without progression of disease after therapy, PCI decreased the 5- and 10-year rate of BM and improved 5- and 10-year DFS, but did not improve OS. Although this study did not meet its primary end point, the long-term results reveal many important findings that will benefit future trials. Identifying the appropriate patient population and a safe intervention is critical. Trial Registration ClinicalTrials.gov identifier: NCT00048997.
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Affiliation(s)
- Alexander Sun
- Princess Margaret Cancer Centre, Toronto, Ontario, Canada
| | - Chen Hu
- NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.,Johns Hopkins University School of Medicine, Baltimore, Maryland
| | | | | | | | - Swati Dutta
- Michigan Cancer Research Consortium CCOP, Ann Arbor
| | | | | | | | - Hak Choy
- University of Texas Southwestern Medical Center, Dallas
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Real-World Adherence to Guideline-Recommended Treatment for Small Cell Lung Cancer. Am J Clin Oncol 2019; 43:236-242. [DOI: 10.1097/coc.0000000000000657] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/26/2023]
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Kim TG, Pyo H, Ahn YC, Noh JM, Oh D. Role of prophylactic cranial irradiation for elderly patients with limited-disease small-cell lung cancer: inverse probability of treatment weighting using propensity score. JOURNAL OF RADIATION RESEARCH 2019; 60:630-638. [PMID: 31165148 PMCID: PMC6805975 DOI: 10.1093/jrr/rrz040] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/02/2019] [Revised: 03/26/2019] [Indexed: 06/09/2023]
Abstract
Studies of prophylactic cranial irradiation (PCI) focused on elderly patients with small-cell lung cancer (SCLC) are rarely conducted. We aimed to identify whether there is a survival benefit of prophylactic cranial irradiation (PCI) in elderly patients using a single institution's retrospective data. A total of 234 patients with limited-disease SCLC (LD-SCLC) treated with thoracic chemoradiotherapy were evaluated; of these, 139 patients received PCI. To minimize treatment selection bias, patients were adjusted using the propensity score on factors associated with receipt of PCI. Cox proportional hazard model and Kaplan-Meier analyses were used to identify which subgroup may benefit from PCI. Median follow-up time was 22 months (range 1-150 months). PCI was associated with favorable brain metastasis-free survival, disease-specific survival, and overall survival in the entire population [hazard ratios (HR) 0.588, 95% confidence interval (CI) 0.338-1.024, P = 0.060; HR 0.477, 95% CI 0.331-0.687, P < 0.001; HR 0.543, 95% CI 0.383-0.771, P = 0.001, respectively). However, PCI had no significant relationship with overall survival in patients aged ≥65 years with cT3-4 disease and/or females gender (HR 0.817, 95% CI 0.098-6.849, P = 0.853; HR 1.082, 95% CI 0.114-10.227, P = 0.946, respectively). The benefits and risks of PCI in elderly patients with LD-SCLC need to be scrutinized, especially in those with high T stage tumors and/or females.
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Affiliation(s)
- Tae Gyu Kim
- Department of Radiation Oncology, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Korea
| | - Hongryull Pyo
- Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Yong Chan Ahn
- Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Jae Myoung Noh
- Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Dongryul Oh
- Departments of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
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