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Li X, Lu S, Lv J, Guan S, Yan M, Zhu H, Cao J, Zhao L. The role of prophylactic cranial irradiation in patients with limited-stage small cell lung cancer at different risks of brain metastasis: A multicenter retrospective study. Radiother Oncol 2025; 208:110897. [PMID: 40254167 DOI: 10.1016/j.radonc.2025.110897] [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: 02/06/2024] [Revised: 03/20/2025] [Accepted: 04/11/2025] [Indexed: 04/22/2025]
Abstract
BACKGROUND AND PURPOSE To evaluate the value of prophylactic cranial irradiation (PCI) in patients with limited-stage small cell lung cancer (LS-SCLC) at different risks of brain metastasis (BM). MATERIALS AND METHODS A retrospective study included 498 LS-SCLC patients from three centers who achieved complete or partial response (CR/PR) after radical chemoradiotherapy. A nomogram was developed using significant factors associated with BM, identified through univariate and multivariate analyses. Patients were stratified into high- and low-risk groups based on risk scores. The incidence of BM was compared between patients with and without PCI in different risk-stratified populations using the log-rank test. RESULTS The nomogram included age, start of treatment to the end of radiotherapy (SER), hemoglobin, prognostic nutritional index (PNI), ProGRP, and NSE. The area under the receiver operating characteristics (AUC) of the nomogram for predicting the 2-year probability of intracranial progression-free survival (IPFS) were 0.738, 0.811, and 0.726 in the training, internal validation, and external validation cohorts, respectively. In the low-risk group, no significant differences were observed in BM incidence (p = 0.220), OS (p = 0.679), or PFS (p = 0.616) between PCI and non-PCI groups. In the high-risk group, PCI significantly reduced BM incidence (p < 0.0001) and improved PFS (p = 0.032), while no significant differences were found in OS (p = 0.778). Propensity score-matching analysis showed similar results. CONCLUSION PCI did not improve OS in patients regardless of high or low risk of BM. However, PCI did significantly reduce the incidence of BM and prolong PFS in patients at a high risk of BM.
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Affiliation(s)
- Xingyue Li
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Shuangqing Lu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Jingli Lv
- Department of Medical Editor, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China
| | - Song Guan
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Meng Yan
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China
| | - Hui Zhu
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong Province, China
| | - Jianzhong Cao
- Department of Radiotherapy, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan, China.
| | - Lujun Zhao
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, China.
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Yin X, Lin X, Zhang G, Yin Y, Sun T. Intensity-modulated proton therapy for hippocampal-sparing prophylactic cranial irradiation: a planning comparison with photon therapy. BMC Cancer 2025; 25:639. [PMID: 40200186 PMCID: PMC11980109 DOI: 10.1186/s12885-025-14039-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2024] [Accepted: 03/28/2025] [Indexed: 04/10/2025] Open
Abstract
BACKGROUND The purpose of the study was to evaluate the dosimetric characteristics of volumetric modulated arc therapy (VMAT), helical tomotherapy (HT), and intensity-modulated proton therapy (IMPT) and to compare the dosimetric differences between the two IMPT plans with coplanar and non-coplanar beams in prophylactic cranial irradiation (PCI) with hippocampal-sparing for small cell lung cancer (SCLC). METHODS Twenty-five patients diagnosed with limited-stage SCLC and received PCI were enrolled in the study. Four treatment plans were designed: VMAT, HT, and two IMPT plans with coplanar and non-coplanar beams (referred to as IMPT-cop and IMPT-noncop, respectively). The prescription dose was 25 Gy in 2.5 Gy(RBE) fractions. The PTV was optimized in both the VMAT and HT plans. In IMPT plans, multifield optimization and CTV robust optimization with a 3-mm setup uncertainty and 3.5% range uncertainty were used. According to the RTOG 0933 protocol, the dose limits for the hippocampus were the dose received by 100% volume (D100) ≤ 9 Gy and the maximum dose (Dmax) ≤ 16 Gy. RESULTS For the target, the two IMPT plans significantly improved the V100, D98, the homogeneity index (HI) and gradient index (GI) compared with VMAT and HT plans. The HT plans showed the highest conformity index (CI) compared to the other three plans. The two IMPT plans significantly reduced the D100, Dmax and Dmean of the hippocampus, the mean dose of bilateral eyeballs and parotids, the maximum dose of bilateral lenses and lenses PRV compared to the VMAT and HT plans. For D100 in hippocampus, the IMPT-cop and IMPT-noncop plans reduced by 43.23%, 42.55%, 41.14%, and 40.43%, respectively, relative to VMAT and HT plans. For Dmax in hippocampus, the IMPT-cop and IMPT-noncop plans decreased by 8.22%, 8.29%, 7.86%, and 7.93%, respectively, relative to VMAT and HT plans. For hippocampal Dmean, IMPT-cop and IMPT-noncop plans decreased by 23.1%, 22.48%, 20.55%, and 19.91% compared with VMAT and HT plans, respectively. VMAT plans showed the lowest values for the maximum dose to the bilateral eyeballs among the four plans. When comparing the two IMPT plans, IMPT-cop plans significantly reduced the mean dose to the hippocampus, and increased the Dmean and Dmax of bilateral eyeballs, and the Dmax of bilateral lenses and lenses PRV compared to IMPT-noncop plans. CONCLUSIONS Compared with photon plans, proton plans significantly reduce the dose to the hippocampus, lenses, eyeballs and parotids in hippocampal-sparing PCI. Compared to IMPT plans with coplanar beams, IMPT plans with non-coplanar beams have shown dosimetric advantages in eyeballs and lenses, with no benefit for dose sparing in the hippocampus.
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Affiliation(s)
- Xiaoyan Yin
- Department of Radiation Oncology and Shandong Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Science, Jinan, China
| | - Xiutong Lin
- Department of Radiation Physics, Shandong Second Provincial General Hospital, Jinan, China
| | - Guifang Zhang
- Department of Radiation Physics, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China
| | - Yong Yin
- Department of Radiation Physics, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China
| | - Tao Sun
- Department of Radiation Physics, Shandong Cancer Hospital and Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, China.
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Marwaha AS, Liang Y, Shepard MJ, Yu A, Karlovits SM, Wegner RE. Patterns of failure after stereotactic radiosurgery for brain metastases from small cell lung cancer: outcomes in the immunotherapy era. J Neurooncol 2025; 172:177-183. [PMID: 39643852 DOI: 10.1007/s11060-024-04895-w] [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: 10/29/2024] [Accepted: 11/20/2024] [Indexed: 12/09/2024]
Abstract
PURPOSE/OBJECTIVE(S) Small cell lung cancer (SCLC) is known to have high rates of development of brain metastases. Standard treatment has been whole brain radiation therapy (WBRT) but the role for more focused treatment and hippocampal avoidance has arisen in the past decade. In addition, with possible penetration of the central nervous system by more modern immunotherapies, the risk of distant failure may be lower. As such, we reviewed patients at our institution treated with stereotactic radiosurgery (SRS) to look at patterns, locations, and predictors of failure in the brain. MATERIALS/METHODS A retrospective review and analysis of charts was done on 46 patients treated with SRS (no history of prior WBRT) for their brain metastases from SCLC. Multivariate analysis was used to determine significant prognostic factors influencing survival and local/distant failure. We tracked timing and type of immunotherapy, if any, as well as if patients failed in the hippocampus or required WBRT. RESULTS There were 46 patients with 97 total brain metastases treated with SRS in this study. Median number of metastases was 2 (1-5). The median dose of radiation was 20 Gy (20-30) in 3 fractions (1-5) for all 97 tumors. 11 patients did not receive immunotherapy, whereas 35 patients had immunotherapy of some sort. Median overall survival (OS) for the entire cohort was 13 months, with a 12 month OS of 59% and 2 year OS of 30%. Cox regression did not reveal any significant predictors of OS, including age, sex, total volume, extracranial disease, KPS, immunotherapy, or number of metastases. 12 month and 24 month local control of disease was 95% and 80%, respectively. There were no significant predictors of local failure including volume, dose, or immunotherapy. 25 of the patients had distant brain failure, with a rate of distant failure of 38% and 64% for 6 and 12 months, respectively. Immunotherapy, number of metastases, total target volume, nor presence of extracranial disease was predictive of distant brain failure. WBRT free survival was also measured and found to be 73% at 1 year. There were no significant predictors for this measure. Lastly, five patients in this cohort showed failure in the hippocampus, where the rate of failure at 6 and 12 months was 16%. CONCLUSION Rates of distant brain failure in SCLC patients after SRS remain similar to those of NSCLC patients in the immunotherapy era. We did not show a decrease in distant failure rate based on immunotherapy use. The rate of hippocampal failure was quite low and should provide reassurance that SRS and techniques such as HA-IMRT can be reasonably used in these patients. Ongoing clinical trials will help provide more definitive answers in this arena.
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Affiliation(s)
- Alexander S Marwaha
- Department of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, USA.
| | - Yun Liang
- Department of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, USA
| | - Matthew J Shepard
- Department of Neurosurgery, Allegheny Health Network, Pittsburgh, USA
| | - Alexander Yu
- Department of Neurosurgery, Allegheny Health Network, Pittsburgh, USA
| | - Stephen M Karlovits
- Department of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, USA
| | - Rodney E Wegner
- Department of Radiation Oncology, Allegheny Health Network Cancer Institute, Pittsburgh, USA.
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Ito K, Nakajima Y, Minakami S, Machitori Y, Hosomi Y, Hashimoto K, Saito M, Murofushi KN. Prophylactic cranial irradiation for limited-stage small-cell lung cancer in the modern magnetic resonance imaging era may be omitted: a propensity score-matched analysis. JOURNAL OF RADIATION RESEARCH 2024; 65:805-812. [PMID: 39478663 PMCID: PMC11630028 DOI: 10.1093/jrr/rrae087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/30/2024] [Revised: 09/25/2024] [Indexed: 12/12/2024]
Abstract
We aimed to clarify whether prophylactic cranial irradiation (PCI) is associated with improved outcomes in limited-stage small-cell lung cancer (LS-SCLC) in the current era of magnetic resonance imaging (MRI). Data from patients with LS-SCLC who achieved a complete response to definitive chemoradiotherapy (CRT) at two medical centers were retrospectively reviewed. Propensity score-matching was performed in a 2:1 ratio to balance the baseline characteristics of the no-PCI and PCI groups. The endpoints were the incidence of brain metastasis (BM), neurological causes of death and overall survival (OS). Overall, 80% patients underwent head MRI during the initial staging and 75 patients (no-PCI, n = 50; PCI, n = 25) were matched. Their baseline characteristics were generally well-balanced except for age; patients in the no-PCI group tended to be older. The median follow-up period was 29 months. Although the incidence of BMs tended to be higher in the no-PCI group (1-year BM occurrence: 26% vs 17%, P = 0.22), the incidence of multiple BMs (defined as >4 metastases) was similar between groups (1-year multiple BMs occurrence: 8% vs 9%, P = 0.65). The 2-year neurological causes of death and OS rate did not significantly differ between the groups (6% and 9%; P = 0.85; and 70% and 79%; P = 0.36, respectively). The 1-year occurrence of multiple BMs did not increase, even without PCI, when modern imaging modalities were integrated into the initial diagnosis, suggesting that PCI could be omitted after CRT, if MRI was incorporated into the initial diagnosis and follow-up.
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Affiliation(s)
- Kei Ito
- Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
| | - Yujiro Nakajima
- Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
- Department of Radiological Sciences, Komazawa University, 1-23-1 Komazawa, Setagaya-ku, Tokyo 154-8525, Japan
| | - Shota Minakami
- Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
- Department of Radiology, Tokyo Metropolitan Bokutoh Hospital, 4-23-15 Kotobashi, Sumida-ku, Tokyo 130-8575, Japan
| | - Yumiko Machitori
- Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
- Department of Radiology, Tokyo Metropolitan Bokutoh Hospital, 4-23-15 Kotobashi, Sumida-ku, Tokyo 130-8575, Japan
| | - Yukio Hosomi
- Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
| | - Kana Hashimoto
- Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
| | - Makoto Saito
- Division of Clinical Research Support, Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
| | - Keiko Nemoto Murofushi
- Division of Radiation Oncology, Department of Radiology, Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, 3-18-22 Honkomagome, Bunkyo-ku, Tokyo 113-8677, Japan
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Hu Y, Lei W, Xin E, Cheng T, Liu J, Tang Y, Lai Y, Yu H, Tan Y, Yang J, Huang J, Liu D, Zhang J. Factors associated with the distribution of brain metastases in lung cancer: a retrospective study. Clin Exp Metastasis 2024; 41:959-969. [PMID: 39352614 DOI: 10.1007/s10585-024-10315-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2024] [Accepted: 09/16/2024] [Indexed: 12/01/2024]
Abstract
The distribution of brain metastases (BMs) in patients with lung cancer may be associated with the primary tumor-related factors and cerebral small vascular diseases (CSVDs). The aim of this study was to investigate the potential effects of the above factors on the distribution of BMs. A total of 5,788 lesions in 823 patients with BMs from lung cancer were enrolled. The numbers of BMs and CSVDs in 15 brain regions were determined. CSVDs include recent small subcortical infarcts (RSSIs), perivascular spaces, and lacunes of presumed vascular origin (LPVOs). We collected the number of CSVDs, and primary tumor-related factors (including clinical and imaging features) in lung cancer patients with BMs. Univariate and multivariate linear regression were utilized to analyze the potential influence of the above factors on the number of BMs in 15 brain regions. In addition, we performed subgroup analyses of all patients with adenocarcinoma (AD), female patients with AD, male patients with AD, and patients with small cell lung cancer. Univariate linear regression analyses showed that bone metastasis, adrenal metastasis, RSSIs, and LPVOs were associated with the number of BMs in over half of the examined brain regions. Only the independent association of LVPOs persisted in the multivariate linear regression analyses, and similar phenomenon was found in the subgroup analyses. In conclusion, the distribution of BMs in lung cancer patients appears to be associated with the presence of LVPOs, while primary tumor-related factors have less influence.
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Affiliation(s)
- Yixin Hu
- Department of Radiology, School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, 400030, People's Republic of China
| | - Weiwei Lei
- Department of Critical Care Medicine, School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, 400030, People's Republic of China
| | - Enhui Xin
- Department of Research and Development, Shanghai United Imaging Intelligence Co., Ltd., Shanghai, 200232, People's Republic of China
| | - Tan Cheng
- Department of Radiology, School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, 400030, People's Republic of China
| | - Jiang Liu
- Department of Radiology, School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, 400030, People's Republic of China
| | - Yu Tang
- Department of Radiology, School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, 400030, People's Republic of China
| | - Yong Lai
- Department of Radiology, School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, 400030, People's Republic of China
| | - Hong Yu
- Department of Radiology, School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, 400030, People's Republic of China
| | - Yong Tan
- Department of Radiology, School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, 400030, People's Republic of China
| | - Jing Yang
- Department of Radiology, School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, 400030, People's Republic of China
| | - Junhao Huang
- Department of Radiology, School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, 400030, People's Republic of China
| | - Daihong Liu
- Department of Radiology, School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, 400030, People's Republic of China.
| | - Jiuquan Zhang
- Department of Radiology, School of Medicine, Chongqing University Cancer Hospital, Chongqing University, Chongqing, 400030, People's Republic of China.
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Chen M, Sun Z, Pan J, Xu Y, Wang Y, Chen M, Hu X. The impact of Prophylactic cranial irradiation on the prognosis of patients with limited-stage small cell lung cancer in the MRI era. Radiat Oncol 2024; 19:162. [PMID: 39543706 PMCID: PMC11566379 DOI: 10.1186/s13014-024-02557-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Accepted: 11/09/2024] [Indexed: 11/17/2024] Open
Abstract
PURPOSES To evaluate the impact of prophylactic cranial irradiation (PCI) on the prognosis of patients with limited-stage small cell lung cancer (SCLC) in the era of MRI surveillance. METHODS Limited-stage SCLC patients with complete remission (CR) or partial remission (PR) of tumor after definitive chemo-radiotherapy (CRT) were retrospectively analyzed. Survival data were calculated by Kaplan-Meier methods, Cox proportional hazards model was applied for multivariate prognostic analysis. RESULTS Between June 2002 and January 2017, 620 patients with limited-stage SCLC were accrued in our study. After CRT, 228 (36.8%) patients achieved CR, of whom, 29 patients did not receive PCI, among the rest 199 patients, 172 (86.4%) received brain MRI to exclude brain metastasis (BM) before PCI. With a median follow-up time of 25.6 months, the cumulative BM rate was 17.1% and 37.9% in patients who received or did not receive PCI (P = 0.011). The median survival time was 30.2 months and 30.5 months, respectively and the 1 -, 3 -, 5-year survival rates were 93.7%, 42.9%, 35.8% and 83.4%, 46.5%, 41.9%, respectively (P = 0.98). Multivariate analysis indicated that baseline KPS ≥ 90 was a favorable independent prognostic factor for OS in CR patients (HR: 0.33, 95% CI: 0.23-0.46, P = 0.000). After CRT, 392 (63.2%) patients achieved PR, 53 cases did not receive PCI and 310 (91.4%) of the remaining 339 patients received brain MRI before PCI. With a median follow-up time of 15.5 months, the cumulative brain metastasis rate was 12.7% and 46.2% respectively (P = 0.000). The median survival time was 25.7 months and 18.6 months, respectively. The 1 -, 3 -, and 5-year survival rates were 87.6%, 40.2%, 29.2% and 75.7%, 16.7%, 10.3% (P = 0.000). Baseline KPS ≥ 90 (HR: 0.32, 95% CI: 0.25-0.41, P = 0.000) and PCI (HR: 0.57, 95% CI: 0.41-0.79, P = 0.001) were favorable prognostic factors for OS in PR patients. CONCLUSIONS In this study, PCI significantly reduced the incidence of BM in patients with limited-stage SCLC who were evaluated as CR and PR after CRT, but it has no significantly positive impact on overall survival in CR patients. Further prospective randomized studies were warranted.
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Affiliation(s)
- Mengyuan Chen
- Hangzhou Institute of Medicine (HIM), Zhejiang Cancer Hospital, Chinese Academy of Sciences, Hangzhou, P. R. China
| | - Zehua Sun
- Hangzhou Institute of Medicine (HIM), Zhejiang Cancer Hospital, Chinese Academy of Sciences, Hangzhou, P. R. China
| | - Jingcong Pan
- Hangzhou Institute of Medicine (HIM), Zhejiang Cancer Hospital, Chinese Academy of Sciences, Hangzhou, P. R. China
| | - Yujin Xu
- Hangzhou Institute of Medicine (HIM), Zhejiang Cancer Hospital, Chinese Academy of Sciences, Hangzhou, P. R. China
| | - Yuezhen Wang
- Hangzhou Institute of Medicine (HIM), Zhejiang Cancer Hospital, Chinese Academy of Sciences, Hangzhou, P. R. China
| | - Ming Chen
- State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, P. R. China.
- United Laboratory of Frontier Radiotherapy Technology of Sun Yat-Sen University & Chinese Academy of Sciences Ion Medical Technology Co, Ltd, Guangzhou, P. R. China.
| | - Xiao Hu
- Hangzhou Institute of Medicine (HIM), Zhejiang Cancer Hospital, Chinese Academy of Sciences, Hangzhou, P. R. China.
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Chen M, Li R, Kong Y, Shi L, Wang J, Wang Y, Xu Y, Ji Y, Hu X. Rational and design of prophylactic cranial irradiation (PCI) and brain MRI surveillance versus brain MRI surveillance alone in patients with limited-stage small cell lung cancer achieving complete remission (CR) of tumor after chemoradiotherapy: a multicenter prospective randomized study. BMC Cancer 2024; 24:429. [PMID: 38589800 PMCID: PMC11000402 DOI: 10.1186/s12885-024-12123-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2023] [Accepted: 03/14/2024] [Indexed: 04/10/2024] Open
Abstract
BACKGROUND Prophylactic cranial irradiation (PCI) is part of standard care in limited-stage small cell lung cancer (SCLC) at present. As evidence from retrospective studies increases, the benefits of PCI for limited-stage SCLC are being challenged. METHODS A multicenter, prospective, randomized controlled study was designed. The key inclusion criteria were: histologically or cytologically confirmed small cell carcinoma, age ≥ 18 years, KPS ≥ 80, limited-stage is defined as tumor confined to one side of the chest including ipsilateral hilar, bilateral mediastinum and supraclavicular lymph nodes, patients have received definitive thoracic radiotherapy (regardless of the dose-fractionation of radiotherapy used) and chemotherapy, evaluated as complete remission (CR) of tumor 4-6 weeks after the completion of chemo-radiotherapy. Eligible patients will be randomly assigned to two arms: (1) PCI and brain MRI surveillance arm, receiving PCI (2.5 Gy qd to a total dose of 25 Gy in two weeks) followed by brain MRI surveillance once every three months for two years; (2) brain MRI surveillance alone arm, undergoing brain MRI surveillance once every three months for two years. The primary objective is to compare the 2-year brain metastasis-free survival (BMFS) rates between the two arms. Secondary objectives include 2-year overall survival (OS) rates, intra-cranial failure patterns, 2-year progression-free survival rates and neurotoxicity. In case of brain metastasis (BM) detect during follow-up, stereotactic radiosurgery (SRS) will be recommended if patients meet the eligibility criteria. DISCUSSION Based on our post-hoc analysis of a prospective study, we hypothesize that in limited-stage SCLC patients with CR after definitive chemoradiotherapy, and ruling out of BM by MRI, it would be feasible to use brain MRI surveillance and omit PCI in these patients. If BM is detected during follow-up, treatment with SRS or whole brain radiotherapy does not appear to have a detrimental effect on OS. Additionally, this approach may reduce potential neurotoxicity associated with PCI.
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Affiliation(s)
- Mengyuan Chen
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Runhua Li
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Yue Kong
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Lei Shi
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Jing Wang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Yuezhen Wang
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Yujin Xu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Yongling Ji
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China
| | - Xiao Hu
- Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, 310022, China.
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Seo SH, Pyo H, Ahn YC, Oh D, Yang K, Kim N, Sun JM, Park S, Jung HA, Lee SH, Ahn JS, Ahn MJ, Noh JM. Pulmonary function and toxicities of proton versus photon for limited-stage small cell lung cancer. Radiat Oncol J 2023; 41:274-282. [PMID: 38185932 PMCID: PMC10772597 DOI: 10.3857/roj.2023.00773] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2023] [Revised: 09/26/2023] [Accepted: 10/10/2023] [Indexed: 01/09/2024] Open
Abstract
PURPOSE We aimed to compare the oncological outcomes and toxicities of definitive proton beam therapy (PBT) and photon beam therapy in patients with limited-stage small cell lung cancer (LS-SCLC). MATERIALS AND METHODS We retrospectively reviewed 262 patients with newly diagnosed LS-SCLC who underwent definitive PBT (n = 20; proton group) or photon beam therapy (n = 242; photon group) with concurrent chemotherapy between January 2016 and February 2021 and compared overall survival (OS), progression-free survival (PFS), dose-volume parameters, and toxicities between the groups. RESULTS The median follow-up duration was 24.5 months (range, 3.7 to 78.7). Baseline lung function was significantly worse and clinical target volume (CTV) was larger in the proton group (CTV: 296.6 vs. 215.3 mL; p = 0.080). The mean lung V10 was 37.7% ± 16.8% and 51.6% ± 24.5% in the proton and photon groups, respectively (p = 0.002). Two-year OS and PFS rates were 57.2% and 35.7% in the proton group and 65.3% and 40.8% in the photon group, respectively (p = 0.542 and 0.748, respectively). Grade ≥2 radiation pneumonitis and esophagitis occurred in 5 (25.0%) and 7 (35.0%) PBT-treated patients and 66 (27.3%) and 40 (16.5%) photon beam therapy-treated patients, respectively (p = 0.826 and 0.062, respectively). CONCLUSION Although the proton group had poorer lung function and a larger CTV than that in the photon group, both groups exhibited comparable treatment outcomes and radiation-related toxicities in LS-SCLC. PBT may be a valuable therapeutic modality in patients with poor pulmonary function or extensive disease burden owing to its lung-sparing ability.
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Affiliation(s)
- Sang Hoon Seo
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hongryull Pyo
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Yong Chan Ahn
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Dongryul Oh
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Kyungmi Yang
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Nalee Kim
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jong-Mu Sun
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sehhoon Park
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Hyun Ae Jung
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Se-Hoon Lee
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jin Seok Ahn
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Myung-Ju Ahn
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae Myoung Noh
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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Carlisle JW, Leal T. Advancing immunotherapy in small cell lung cancer. Cancer 2023; 129:3525-3534. [PMID: 37602492 DOI: 10.1002/cncr.34977] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Revised: 06/26/2023] [Accepted: 06/28/2023] [Indexed: 08/22/2023]
Abstract
Small cell lung cancer (SCLC) is a rapidly progressive neuroendocrine carcinoma that, until recently, had a very small armamentarium of effective treatments. Advances in DNA sequencing and whole transcriptomics have delineated key subtypes; therefore, SCLC is no longer viewed as a homogeneous cancer. Chemoimmunotherapy with PD1 blockade is now the standard of care for advanced disease, and ongoing research efforts are moving this strategy into the limited stage setting. Combination strategies of immunotherapy with radiation are also under active clinical trial in both limited and extensive stage disease. PLAIN LANGUAGE SUMMARY: Small cell lung cancer (SCLC) is a rapidly progressive neuroendocrine carcinoma that, until recently, had a very small armamentarium of effective treatments. Chemoimmunotherapy with immune check point inhibitors is now the standard of care for advanced disease. This comprehensive review provides an overview of current treatment strategies for SCLC, unmet needs in this patient population, and emerging treatment strategies incorporating immunotherapy that will hopefully further improve outcomes for patients.
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Affiliation(s)
- Jennifer W Carlisle
- Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA
| | - Ticiana Leal
- Department of Hematology and Medical Oncology, Thoracic Medical Oncology Program, Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia, USA
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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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11
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Pan L, Fan X, Wang L, Wang Y, Li Y, Cui Y, Zheng H, Yi Q, Wu K. Prophylactic cranial irradiation for limited-stage small-cell lung cancer in the magnetic resonance imaging era. Cancer Med 2023; 12:2484-2492. [PMID: 35894822 PMCID: PMC9939136 DOI: 10.1002/cam4.5082] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Revised: 06/17/2022] [Accepted: 07/14/2022] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND We investigated the role of prophylactic cranial irradiation (PCI) in limited-stage small-cell lung cancer (LS-SCLC) according to tumor response in the magnetic resonance imaging (MRI) era. METHODS We retrospectively evaluated patients with LS-SCLC without brain metastases (BMs) on MRI who achieved either complete response (CR) or partial response (PR) after initial chemoradiotherapy at our center from 2006 to 2017. RESULTS This study comprised 116 patients (median age, 58 years; men, 92; women, 24). After initial chemoradiotherapy, 53 patients achieved CR, while 63 patients achieved PR. Eighty-three patients received PCI. Patients who received PCI had better overall survival (OS, 5-year: 52.5% vs. 35.1%; p = 0.012) and progression-free survival (PFS, 5-year: 45.0% vs. 28.2%; p = 0.001) and a lower incidence of BMs (5-year: 18.3% vs. 39.4%; p = 0.010). In the subgroup analysis, PCI improved OS (5-year: 67.8% vs. 46.7%, p = 0.005) and PFS (5-year: 65.2% vs. 35.0%, p = 0.021) and decreased BM risk (5-year: 12.1% vs. 52.4%, p = 0.002) for patients with CR. However, PCI had no benefit (5-year OS: 40.5% vs. 35.6%, p = 0.763; 5-year BMs: 24.6% vs. 31.9%, p = 0.561) for patients with PR. CONCLUSIONS Tumor response remained an important factor for selecting patients for PCI in the MRI era. PCI should be recommended for patients with LS-SCLC who achieve CR after initial thoracic chemoradiotherapy.
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Affiliation(s)
- Lihua Pan
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of OncologyAffiliated Hospital of Jining Medical UniversityJiningShandongChina
| | - Xingwen Fan
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
- Shanghai Key Laboratory of Radiation OncologyShanghaiChina
| | - Lifang Wang
- Department of OncologyAffiliated Hospital of Jining Medical UniversityJiningShandongChina
| | - Yihua Wang
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
- Shanghai Key Laboratory of Radiation OncologyShanghaiChina
| | - Yaqi Li
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
- Shanghai Key Laboratory of Radiation OncologyShanghaiChina
| | - Yingshan Cui
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
- Shanghai Key Laboratory of Radiation OncologyShanghaiChina
| | - Hong Zheng
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
- Shanghai Key Laboratory of Radiation OncologyShanghaiChina
| | - Qiong Yi
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
- Shanghai Key Laboratory of Radiation OncologyShanghaiChina
| | - Kailiang Wu
- Department of Radiation OncologyFudan University Shanghai Cancer CenterShanghaiChina
- Department of Oncology, Shanghai Medical CollegeFudan UniversityShanghaiChina
- Shanghai Key Laboratory of Radiation OncologyShanghaiChina
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12
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Wang C, Mu S, Yang X, Li L, Tao H, Zhang F, Li R, Hu Y, Wang L. Outcome of immune checkpoint inhibitors in patients with extensive-stage small-cell lung cancer and brain metastases. Front Oncol 2023; 13:1110949. [PMID: 37213269 PMCID: PMC10196483 DOI: 10.3389/fonc.2023.1110949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Accepted: 04/17/2023] [Indexed: 05/23/2023] Open
Abstract
Objectives Brain metastases (BMs) are common in extensive-stage small-cell lung cancer (SCLC) and are underrepresented in pivotal clinical trials that demonstrate the efficacy of immune checkpoint inhibitors (ICIs). We conducted a retrospective analysis to assess the role of ICIs in BM lesions in less selected patients. Materials and methods Patients with histologically confirmed extensive-stage SCLC who were treated with ICIs were included in this study. Objective response rates (ORRs) were compared between the with-BM and without-BM groups. Kaplan-Meier analysis and the log-rank test were used to evaluate and compare progression-free survival (PFS). The intracranial progression rate was estimated using the Fine-Gray competing risks model. Results A total of 133 patients were included, 45 of whom started ICI treatment with BMs. In the whole cohort, the overall ORR was not significantly different for patients with and without BMs (p = 0.856). The median progression-free survival for patients with and without BMs was 6.43 months (95% CI: 4.70-8.17) and 4.37 months (95% CI: 3.71-5.04), respectively (p =0.054). In multivariate analysis, BM status was not associated with poorer PFS (p = 0.101). Our data showed that different failure patterns occurred between groups, with 7 patients (8.0%) without BM and 7 patients (15.6%) with BM having intracranial-only failure as the first site progression. The cumulative incidences of brain metastases at 6 and 12 months were 15.0% and 32.9% in the without-BM group and 46.2% and 59.0% in the BM group, respectively (Gray's p<0.0001). Conclusions Although patients with BMs had a higher intracranial progression rate than patients without BMs, the presence of BMs was not significantly associated with a poorer ORR and PFS with ICI treatment in multivariate analysis.
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Affiliation(s)
- Chunyu Wang
- Department of Oncology, The First Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Department of Oncology, The Fifth Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
| | - Shuai Mu
- Department of Oncology, The First Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Department of Oncology, The Fifth Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
| | - Xuhui Yang
- Department of Oncology, The Fifth Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Department of Oncology, Chinese PLA Medical School, Beijing, China
| | - Lingling Li
- Department of Oncology, Chinese PLA Medical School, Beijing, China
| | - Haitao Tao
- Department of Oncology, The First Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Department of Oncology, The Fifth Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
| | - Fan Zhang
- Department of Oncology, The First Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Department of Oncology, The Fifth Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
| | - Ruixin Li
- Department of Oncology, The First Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
| | - Yi Hu
- Department of Oncology, The First Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Department of Oncology, The Fifth Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- *Correspondence: Lijie Wang, ; Yi Hu,
| | - Lijie Wang
- Department of Oncology, The First Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- Department of Oncology, The Fifth Medical Center of Chinese People’s Liberation Army (PLA) General Hospital, Beijing, China
- *Correspondence: Lijie Wang, ; Yi Hu,
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13
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Sun T, Lin X, Li K, Qiu Q, Duan J, Zhang G, Yin Y. Volumetric modulated arc therapy for hippocampal-sparing prophylactic cranial irradiation: Planning comparison of Halcyon and C-arm accelerators. Front Oncol 2023; 13:993809. [PMID: 36959800 PMCID: PMC10028073 DOI: 10.3389/fonc.2023.993809] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 02/06/2023] [Indexed: 03/09/2023] Open
Abstract
Background The purpose of the study was to evaluate the dosimetry of the Halcyon in prophylactic cranial irradiation (PCI) with volumetric modulated arc therapy (VMAT) and hippocampal-sparing for small cell lung cancer (SCLC). Methods Five VMAT plans were designed on CT images of 15 patients diagnosed with SCLC and received PCI. Three plans with two full arcs were generated on the Trilogy and the TrueBeam accelerators, and flattening filter (FF) and flattening filter free (FFF) modes were used on TrueBeam. Two Halcyon plans with two and three full arcs were generated, referred to as H-2A and H-3A, respectively. The prescription dose was 25 Gy in 2.5-Gy fractions. The dose limit for hippocampus were D100 ≤ 9Gy and Dmax ≤ 16Gy. The Wilcoxon matched-paired signed-rank test was used to evaluate the significance of the observed differences between the five plans. Results H-2A plans significantly increased the D2 of PTV, and H-3A plans showed comparable or even better target dosimetry (better conformity) compared to the three plans on C-arm accelerators. Compared to T and TB plans, the two Halcyon plans significantly reduced the D100 and mean doses of bilateral hippocampus, the mean doses of eyeballs, and the maximum doses of lenses. D100 of hippocampus was reduced in TrueBeam plans comparing to Trilogy plans. The FFF plans on TrueBeam also represented advantages in Dmean and D100 of hippocampas, Dmean and Dmax of eyeballs, and the Dmax of lenses compared to FF plans. Halcyon plans and TrueBeam plans with FFF mode increased the MUs compared to FF plans. Comparing to H-2A, the H-3A plans exhibited additional dosimetric advantages, including D2, CI and HI of PTV, as well as the maximum and mean doses of hippocampus and eyeballs, and the maximum doses of optic nerves and brainstem. The two Halcyon plans significantly reduced the delivery time and showed the higher gamma passing rate than the three plans of C-arm accelerators. Conclusions Compared with the C-arm accelerators, the dose of hippocampus and the delivery times on Halcyon are relatively significantly reduced for hippocampal-sparing PCI. Three arcs are recommended for VMAT plans with the Halcyon in hippocampal-sparing PCI.
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Park H, Tseng SC, Sholl LM, Hatabu H, Awad MM, Nishino M. Molecular Characterization and Therapeutic Approaches to Small Cell Lung Cancer: Imaging Implications. Radiology 2022; 305:512-525. [PMID: 36283111 PMCID: PMC9713457 DOI: 10.1148/radiol.220585] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 06/10/2022] [Accepted: 06/14/2022] [Indexed: 01/16/2023]
Abstract
Small cell lung cancer (SCLC) is a highly aggressive malignancy with exceptionally poor prognosis, comprising approximately 15% of lung cancers. Emerging knowledge of the molecular and genomic landscape of SCLC and recent successful clinical applications of new systemic agents have allowed for precision oncology treatment approaches. Imaging is essential for the diagnosis, staging, and treatment monitoring of patients with SCLC. The role of imaging is increasing with the approval of new treatment agents, including immune checkpoint inhibitors, which lead to novel imaging manifestations of response and toxicities. The purpose of this state-of-the-art review is to provide the reader with the latest information about SCLC, focusing on the subtyping of this malignancy (molecular characterization) and the emerging systemic therapeutic approaches and their implications for imaging. The review will also discuss the future directions of SCLC imaging, radiomics and machine learning.
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Affiliation(s)
- Hyesun Park
- From the Departments of Radiology (H.P., S.C.T., H.H., M.N.),
Pathology (L.M.S.), Medical Oncology (M.M.A.), and Medicine (M.M.A.),
Dana-Farber Cancer Institute and Brigham and Women's Hospital, 450
Brookline Ave, Boston, MA 02215
| | | | - Lynette M. Sholl
- From the Departments of Radiology (H.P., S.C.T., H.H., M.N.),
Pathology (L.M.S.), Medical Oncology (M.M.A.), and Medicine (M.M.A.),
Dana-Farber Cancer Institute and Brigham and Women's Hospital, 450
Brookline Ave, Boston, MA 02215
| | - Hiroto Hatabu
- From the Departments of Radiology (H.P., S.C.T., H.H., M.N.),
Pathology (L.M.S.), Medical Oncology (M.M.A.), and Medicine (M.M.A.),
Dana-Farber Cancer Institute and Brigham and Women's Hospital, 450
Brookline Ave, Boston, MA 02215
| | - Mark M. Awad
- From the Departments of Radiology (H.P., S.C.T., H.H., M.N.),
Pathology (L.M.S.), Medical Oncology (M.M.A.), and Medicine (M.M.A.),
Dana-Farber Cancer Institute and Brigham and Women's Hospital, 450
Brookline Ave, Boston, MA 02215
| | - Mizuki Nishino
- From the Departments of Radiology (H.P., S.C.T., H.H., M.N.),
Pathology (L.M.S.), Medical Oncology (M.M.A.), and Medicine (M.M.A.),
Dana-Farber Cancer Institute and Brigham and Women's Hospital, 450
Brookline Ave, Boston, MA 02215
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Liu Y, Jiang S, Lin Y, Yu H, Yu L, Zhang X. Research landscape and trends of lung cancer radiotherapy: A bibliometric analysis. Front Oncol 2022; 12:1066557. [PMID: 36439443 PMCID: PMC9685815 DOI: 10.3389/fonc.2022.1066557] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Accepted: 10/26/2022] [Indexed: 11/27/2024] Open
Abstract
BACKGROUND radiotherapy is one of the major treatments for lung cancer and has been a hot research area for years. This bibliometric analysis aims to present the research trends on lung cancer radiotherapy. METHOD On August 31, 2022, the authors identified 9868 articles on lung cancer radiotherapy by the Web of Science (Science Citation Indexing Expanded database) and extracted their general information and the total number of citations. A bibliometric analysis was carried out to present the research landscape, demonstrate the research trends, and determine the most cited papers (top-papers) as well as top-journals on lung cancer radiotherapy. After that, the authors analyzed the recent research hotspots based on the latest publications in top-journals. RESULTS These 9868 papers were cited a total of 268,068 times. "Durvalumab after chemoradiotherapy in stage III non-small-cell lung cancer" published in 2017 by Antonia et al.was the most cited article (2110 citations). Among the journals, New England Journal of Medicine was most influential. Moreover, J. Clin. Oncol. and Int. J. Radiat. Oncol. Biol. Phys. was both influential and productive. Corresponding authors represented the USA (2610 articles) and China mainland (2060 articles) took part in most publications and articles with corresponding authors from Netherlands were most cited (46.12 citations per paper). Chemoradiotherapy was the hottest research area, and stereotactic body radiotherapy has become a research hotspot since 2006. Radiotherapy plus immunotherapy has been highly focused since 2019. CONCLUSIONS This bibliometric analysis comprehensively and quantitatively presents the research trends and hotspots based on 9868 relevant articles, and further suggests future research directions. The researchers can benefit in selecting journals and in finding potential collaborators. This study can help researchers gain a comprehensive picture of the research landscape, historical development, and recent hotspots in lung cancer radiotherapy and can provide inspiration for future research.
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Affiliation(s)
- Yanhao Liu
- Department of Radiation Oncology, The Affiliated Qingdao Central Hospital of Qingdao University, Qingdao, China
| | | | | | | | | | - Xiaotao Zhang
- Department of Radiation Oncology, The Affiliated Qingdao Central Hospital of Qingdao University, Qingdao, China
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Qiu J, Ke D, Yu Y, Lin H, Zheng Q, Li H, Zheng H, Liu L, Wang Z, Wu Y, Liu T, Li J. A New Nomogram and Risk Stratification of Brain Metastasis by Clinical and Inflammatory Parameters in Stage III Small Cell Lung Cancer Without Prophylactic Cranial Irradiation. Front Oncol 2022; 12:882744. [PMID: 35875127 PMCID: PMC9300937 DOI: 10.3389/fonc.2022.882744] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2022] [Accepted: 05/27/2022] [Indexed: 11/17/2022] Open
Abstract
Background This study was conducted to determine risk factors for developing brain metastasis (BM) and to predict brain metastasis free survival (BMFS) and overall survival (OS) by combining several clinical parameters and inflammatory indexes. Materials and Methods A nomogram and risk stratification were developed based on multivariate analysis results. The prognostic index (PI) predicting the high risk of BM was calculated by multiplying the weighted factor (β coefficient) with each variable. Results Thirty-two of one hundred patients (32.0%) developed BM. Multivariate cox regression analysis revealed that concurrent chemoradiotherapy (CCRT; hazard ratio (HR), 3.356; p = 0.020), monocyte–lymphocyte ratio (MLR; HR, 4.511; p = 0.002), neutrophil–lymphocyte ratio (NLR; HR, 4.023; p = 0.033), and prognostic-nutrition index (PNI; HR, 2.902; p = 0.018) were independent prognostic factors of BMFS. The nomogram has good accuracy in predicting BMFS, and the C-index was 0.73. The ROC curve showed that these risk factors have good discriminant ability. Similarly, tumor location (HR, 1.675; p = 0.035) and MLR (HR, 2.076; p = 0.013) were independent prognostic factors of OS. In the subgroup analysis of OS, the good group had a better prognosis than the other groups. Risk stratification by PI: the high-risk group had worse BMFS than the low-risk group, which also has certain practical significance for clinical practice in OS. Conclusion We developed a nomogram and corresponding risk stratification in stage III SCLC patients who developed BM. This model and risk stratification can help clinicians improve patient treatment management and better deliver personalized therapy.
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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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18
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Zeng H, Zheng D, Witlox WJA, Levy A, Traverso A, Kong FM(S, Houben R, De Ruysscher DKM, Hendriks LEL. Risk Factors for Brain Metastases in Patients With Small Cell Lung Cancer: A Systematic Review and Meta-Analysis. Front Oncol 2022; 12:889161. [PMID: 35756675 PMCID: PMC9226404 DOI: 10.3389/fonc.2022.889161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2022] [Accepted: 04/25/2022] [Indexed: 11/16/2022] Open
Abstract
The use of prophylactic cranial irradiation (PCI) for small cell lung cancer (SCLC) patients is controversial. Risk factors for brain metastasis (BM) development are largely lacking, hampering personalized treatment strategies. This study aimed to identify the possible risk factors for BM in SCLC.We systematically searched the Pubmed database (1 January 1995 to 18 January 2021) according to the PRISMA guidelines. Eligibility criteria: studies reporting detailed BM data with an adequate sample size (randomized clinical trials [RCTs]: N ≥50; non-RCTs: N ≥100) in patients with SCLC. We summarized the reported risk factors and performed meta-analysis to estimate the pooled hazard ratios (HR) if enough qualified data (i.e., two or more studies; the same study type; the same analysis method; and HRs retrievable) were available. In total, 61/536 records were eligible (18 RCTs and 39 non-RCTs comprising 13,188 patients), in which 57 factors were reported. Ten factors qualified BM data for meta-analysis: Limited stage disease (LD) (HR = 0.34, 95% CI: 0.17-0.67; P = 0.002) and older age (≥65) (HR = 0.70, 95% CI: 0.54-0.92; P = 0.01) were associated with less BM; A higher T stage (≥T3) (HR = 1.72, 95% CI: 1.16-2.56; P = 0.007) was a significant risk factor for BM. Male sex (HR = 1.24, 95% CI: 0.99-1.54; P = 0.06) tended to be a risk factor, and better PS (0-1) (HR = 0.66, 95% CI: 0.42-1.02; P = 0.06) tended to have less BM. Smoking, thoracic radiotherapy dose were not significant (P >0.05). PCI significantly decreased BM (P <0.001), but did not improve OS in ED-SCLC (P = 0.81). A higher PCI dose did not improve OS (P = 0.11). The impact on BM was conflicting between Cox regression data (HR = 0.59, 95% CI: 0.26-1.31; P = 0.20) and competing risk regression data (HR = 0.74, 95% CI: 0.55-0.99; P = 0.04). Compared to M0-M1a, M1b was a risk factor for OS (P = 0.01) in ED-SCLC, but not for BM (P = 0.19). As regular brain imaging is rarely performed, high-quality data is lacking. Other factors such as N-stage and blood biomarkers had no qualified data to perform meta-analysis. In conclusion, younger age, higher T stage, and ED are risk factors for BM, suggesting that PCI should be especially discussed in such cases. Individual patient data (IPD) meta-analysis and well-designed RCTs are needed to better identify more risk factors and further confirm our findings. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021228391, identifier CRD42021228391.
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Affiliation(s)
- Haiyan Zeng
- Department of Radiation Oncology (Maastro), GROW School for Oncology, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Danyang Zheng
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Willem J. A. Witlox
- Department of Clinical Epidemiology and Medical Technology Assessment, GROW—School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Antonin Levy
- Department of Radiation Oncology, Gustave Roussy, Villejuif, France
- Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France
| | - Alberto Traverso
- Department of Radiation Oncology (Maastro), GROW School for Oncology, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Feng-Ming (Spring) Kong
- Department of Clinical Oncology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, Hong Kong SAR, China
- Department of Clinical Oncology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China
| | - Ruud Houben
- Department of Radiation Oncology (Maastro), GROW School for Oncology, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Dirk K. M. De Ruysscher
- Department of Radiation Oncology (Maastro), GROW School for Oncology, Maastricht University Medical Center+, Maastricht, Netherlands
| | - Lizza E. L. Hendriks
- Department of Pulmonary Diseases, GROW School for Oncology and Developmental Biology, Maastricht University Medical Center+, Maastricht, Netherlands
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19
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Xue S, Zeng H, Yan S, Wang Q, Jia X. Prophylactic Cranial Irradiation for Extensive-Stage Small-Cell Lung Cancer: A Controversial Area. Front Oncol 2022; 12:772282. [PMID: 35198438 PMCID: PMC8858935 DOI: 10.3389/fonc.2022.772282] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 01/17/2022] [Indexed: 11/13/2022] Open
Abstract
Small-cell lung cancer (SCLC) is a highly aggressive malignant tumor that is prone to lead to the development of brain metastases (BM). The application of prophylactic cranial irradiation (PCI) has been regarded as an important technological advance made in cancer therapy to reduce the occurrence of BM and improve patient survival. The benefits of PCI in the treatment of limited-stage SCLC have been confirmed. However, there has been continuous controversy about the indications and advantages of PCI for extensive-stage SCLC (ES-SCLC) because of the conflicting results from two prospective trials. In this review, we aimed to discuss the relevant controversy and progress made in the clinical application of PCI in ES-SCLC.
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20
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Tomassen ML, Pomp J, van der Stap J, van Lindert AS, Peters M, Belderbos JS, De Ruysscher DK, Lin SH, Verhoeff JJ, van Rossum PS. The overall survival impact of prophylactic cranial irradiation in limited-stage small-cell lung cancer: a systematic review and meta-analysis. Clin Transl Radiat Oncol 2022; 33:145-152. [PMID: 35243025 PMCID: PMC8881197 DOI: 10.1016/j.ctro.2022.02.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 02/06/2022] [Accepted: 02/10/2022] [Indexed: 12/25/2022] Open
Abstract
PCI for LS-SCLC patients has become more controversial. Literature search on PCI impact on overall survival in LS-SCLC yielded 28 studies. Meta-analysis of adjusted HRs revealed pooled HR of 0.62 (95% CI: 0.57–0.69). Findings support PCI in current practice while awaiting prospective trial results. Background Prophylactic cranial irradiation (PCI) for limited-stage small-cell lung cancer (LS-SCLC) patients has become more controversial. Since the publication of the systematic review by Aupérin et al. in 1999, no randomized controlled trials regarding PCI in LS-SCLC have been completed. The aim of this study was to systematically review and meta-analyze the effect of PCI on overall survival (OS) in patients with LS-SCLC. Methods A systematic search was conducted in the databases of MEDLINE (PubMed), Embase and the Cochrane library. Only studies that reported an adjusted hazard ratio (aHR), indicating the effect of PCI versus no PCI on OS (adjusted for confounders) in patients with LS-SCLC were included for critical appraisal and meta-analysis. A pooled aHR estimate was calculated using a random-effects model. Results Pooling of 28 retrospective studies including a total of 18,575 patients demonstrated a significant beneficial effect of PCI versus no PCI on OS with a pooled aHR of 0.62 (95% CI: 0.57–0.69). Substantial heterogeneity of reported aHRs among studies was observed (I2 = 65.9%). Subgroup analyses revealed that this heterogeneity could partly be explained by study sample size. The pooled aHR among 7 versus 21 studies with a sample size of > 300 versus ≤ 300 patients was 0.79 (95% CI: 0.64–0.97) versus 0.56 (95% CI: 0.46–0.69; p < 0.001), respectively. Conclusions This meta-analysis demonstrates a significant beneficial effect of PCI on OS in patients with LS-SCLC. Larger studies reported a milder beneficial effect, possibly due to a decreased risk of model overfitting. Serious risk of selection and confounding bias were of concern due to the lack of prospective trials. These results support the role of PCI in standard clinical practice in patients with LS-SCLC while awaiting results of prospective trials on alternative strategies.
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Affiliation(s)
- Mathijs L. Tomassen
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Jacquelien Pomp
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | | | | | - Max Peters
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - José S.A. Belderbos
- Department of Radiation Oncology, The Netherlands Cancer Institute – Antoni Van Leeuwenhoek Hospital, Amsterdam, the Netherlands
| | - Dirk K.M. De Ruysscher
- Department of Radiation Oncology (Maastro), GROW School for Oncology and Developmental Biology, Maastricht University Medical Centre+, Maastricht, the Netherlands
| | - Steven H. Lin
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston (TX), United States of America
| | - Joost J.C. Verhoeff
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
| | - Peter S.N. van Rossum
- Department of Radiation Oncology, University Medical Center Utrecht, Utrecht, the Netherlands
- Corresponding author.
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21
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Rittberg R, Banerji S, Kim JO, Rathod S, Dawe DE. Treatment and Prevention of Brain Metastases in Small Cell Lung Cancer. Am J Clin Oncol 2021; 44:629-638. [PMID: 34628433 DOI: 10.1097/coc.0000000000000867] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
Central nervous system (CNS) metastasis will develop in 50% of small cell lung cancer (SCLC) patients throughout disease course. Development of CNS metastasis poses a particular treatment dilemma due to the accompanied cognitive changes, poor permeability of the blood-brain barrier to systemic therapy and relatively advanced state of disease. Survival of patients with untreated SCLC brain metastases is generally <3 months with whole brain radiotherapy used as first-line management in most SCLC patients. To prevent development of CNS metastasis prophylactic cranial irradiation (PCI) is recommended in limited stage disease, after response to chemotherapy and radiation, while PCI may be considered in extensive stage disease after favorable response to upfront treatment. Neurocognitive toxicity with whole brain radiotherapy and PCI is a concern and remains difficult to predict. The mechanism of toxicity is likely multifactorial, but a potential mechanism of injury to the hippocampus has led to hippocampal sparing radiation techniques. Treatment of established non-small cell lung cancer CNS metastases has increasingly focused on using stereotactic radiotherapy (SRS) and it is tempting to extrapolate these results to SCLC. In this review, we explore the evidence surrounding the prediction, prevention, detection, and treatment of CNS metastases in SCLC. We further review whether existing evidence supports extrapolating less toxic treatments to SCLC patients with CNS metastases and discuss trials that may shed more light on this question.
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Affiliation(s)
- Rebekah Rittberg
- Department of Internal Medicine, University of Manitoba
- Departments of Hematology and Medical Oncology
| | - Shantanu Banerji
- Department of Internal Medicine, University of Manitoba
- Departments of Hematology and Medical Oncology
- Research Institute in Oncology and Hematology at CancerCare Manitoba, Winnipeg, MB, Canada
| | | | | | - David E Dawe
- Department of Internal Medicine, University of Manitoba
- Departments of Hematology and Medical Oncology
- Research Institute in Oncology and Hematology at CancerCare Manitoba, Winnipeg, MB, Canada
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22
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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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23
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Qi J, Zhang J, Ge X, Wang X, Xu L, Liu N, Zhao L, Wang P. The Addition of Peripheral Blood Inflammatory Indexes to Nomogram Improves the Predictive Accuracy of Survival in Limited-Stage Small Cell Lung Cancer Patients. Front Oncol 2021; 11:713014. [PMID: 34692490 PMCID: PMC8531548 DOI: 10.3389/fonc.2021.713014] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 09/20/2021] [Indexed: 12/25/2022] Open
Abstract
Background Accumulated evidence for systemic inflammation response in several solid tumors prompts a possibility of prediction of patients’ prognosis in a more accessible and valuable manner. However, the prognostic value of peripheral blood inflammatory markers in limited-stage small cell lung cancer (LS-SCLC) remains unclear. Therefore, we investigated the prognostic values of pretreatment inflammatory indexes in LS-SCLC patients. Methods We retrospectively identified 334 patients with LS-SCLC and collected their pretreatment serum levels of neutrophil, platelet, lymphocyte, leukocyte, hemoglobin, and albumin, then neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic inflammation index (SII) were calculated. Patients were dichotomized as low-Risk or high-Risk group based on their corresponding cutoff values. Univariate and multivariate analyses were conducted with a Cox proportional hazards model. The least absolute shrinkage and selection operator (LASSO)-Cox regression analysis was performed to construct the inflammation-related prognostic scoring system named Risk for OS. Nomograms were established to provide prognostic information, allowing for more individualized prediction of survival. Results Higher pretreatment platelet, lymphocyte, and albumin were indicators of favorable overall survival (OS), whereas higher NLR and SII were accompanied by inferior OS. The prognosis of patients with high Risk was significantly worse than that with low Risk in both the training group and the validation group (both p < 0.001). Comparable area under the curve (AUC) values between the training group and the validation group were observed, yielding 1-, 3-, and 5-year OS rates of 67.3% vs. 69.2%, 66.8% vs. 69.5%, and 66.7% vs. 71.4%, respectively. Multivariate analyses revealed that Risk [hazard ratio (HR) = 0.551, p < 0.001] was an independent negative prognostic indicator for OS, which was further verified in the validation set. The addition of Risk to nomogram (C-index = 0.643) harbored improved predictive accuracy for OS when compared with that of clinical factors alone (C-index = 0.606); the AUC values of 1-, 3-, and 5-year OS rates were 71.7% vs. 66.4%, 73.5% vs. 66.6%, and 71.9% vs. 65.6%, respectively. Conclusions Pretreatment peripheral blood inflammatory indexes may be a noninvasive serum biomarker for poor prognosis in LS-SCLC. The addition of Risk to the nomogram model could serve as a more powerful, economical, and practical method to predict survival for patients with LS-SCLC.
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Affiliation(s)
- Jing Qi
- Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Jiaqi Zhang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Xingping Ge
- Department of Radiation Oncology, Yantaishan Hospital, Yantai, China
| | - Xin Wang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Liming Xu
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Ningbo Liu
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Lujun Zhao
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China
| | - Ping Wang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy, National Clinical Research Center for Cancer, Tianjin's Clinical Research Center for Cancer, Tianjin, China
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24
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Yan M, Toh TS, Lindsay PE, Weiss J, Hueniken K, Yeung C, Sugumar V, Pinto D, Tadic T, Sun A, Bezjak A, Cho J, Raman S, Giuliani M, Moraes FY, Liu G, Hope AJ, Lok BH. Limited-stage small cell lung cancer: Outcomes associated with prophylactic cranial irradiation over a 20-year period at the Princess Margaret Cancer Centre. Clin Transl Radiat Oncol 2021; 30:43-49. [PMID: 34296000 PMCID: PMC8282904 DOI: 10.1016/j.ctro.2021.06.009] [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: 06/10/2021] [Accepted: 06/27/2021] [Indexed: 11/25/2022] Open
Abstract
Prophylactic cranial irradiation (PCI) was more commonly used in younger patients. PCI utilization rates did not change throughout our 20-year institutional experience. PCI was associated with improved OS and lower brain metastasis risk, independent of MRI follow-up or era of treatment. For LS-SCLC patients with good thoracic response, PCI remains the standard-of-care. Background & purpose Prophylactic cranial irradiation (PCI) is recommended for limited-stage small-cell lung cancer (LS-SCLC) patients with good response to concurrent chemoradiation. We report our institution’s 20-year experience with this patient population and associated clinical outcomes. Materials & methods A retrospective cohort of consecutive LS-SCLC patients treated with curative intent chemoradiation at our institution (1997–2018) was reviewed. Overall survival (OS) was calculated using the Kaplan-Meier method, and significant covariates determined by the Cox proportional hazards model. Covariates predictive of PCI were determined using Fisher's exact test and the Mann-Whitney test. Brain failure risk (BFR) was calculated using the cumulative incidence method treating death as a competing event. Treatment cohorts (historic vs. contemporary) were stratified by the median year of diagnosis (2005). Results A total of 369 patients with LS-SCLC were identified, of which 278 patients were notionally PCI eligible. PCI was given to 196 patients (71%). Younger age was associated with PCI utilization (p < 0.001). PCI utilization rates did not change between the historic and contemporary treatment era (p = 0.11), whereas magnetic resonance imaging (MRI) use at baseline and follow-up became more prevalent in the contemporary era (p = <0.001). On multivariable analysis, PCI utilization was associated with improved OS (HR 1.88, 95% CI 1.32–2.69) and decreased BFR (HR 4.66, 95% CI 2.58–8.40). Patients who had MRI follow-up had a higher incidence of BFR (HR 0.35, 95% CI 0.18–0.66) in multivariable analyses. Conclusions For LS-SCLC patients at our institution, PCI is more frequently utilized in younger patients, and the utilization rate did not change significantly over the past 20 years. PCI was independently associated with improved OS and lower BFR. Omission of PCI in LS-SCLC patients should not be routinely practiced in the absence of further prospective data.
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Affiliation(s)
- Michael Yan
- Department of Oncology, Cancer Centre of Southeastern Ontario, Queen's University, Kingston, ON, Canada
| | - Tzen S Toh
- The Medical School, University of Sheffield, Sheffield, United Kingdom.,Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Patricia E Lindsay
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
| | - Jessica Weiss
- Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Katrina Hueniken
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada.,Department of Biostatistics, Princess Margaret Cancer Centre, Toronto, ON, Canada
| | - Christy Yeung
- Department of Laboratory Medicine and Pathology, University of Toronto, Toronto, ON, Canada
| | - Vijithan Sugumar
- Department of Physiology and Pharmacology, Western University, London, ON, Canada
| | - Dixon Pinto
- Faculty of Health Sciences, McMaster University, Hamilton, ON, Canada
| | - Tony Tadic
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
| | - Alexander Sun
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
| | - Andrea Bezjak
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
| | - John Cho
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
| | - Srinivas Raman
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
| | - Meredith Giuliani
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
| | - Fabio Ynoe Moraes
- Department of Oncology, Cancer Centre of Southeastern Ontario, Queen's University, Kingston, ON, Canada
| | - Geoffrey Liu
- Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, Toronto, ON, Canada.,Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.,Institute of Medical Science, University of Toronto, Toronto, ON, Canada
| | - Andrew J Hope
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada
| | - Benjamin H Lok
- Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, ON, Canada.,Department of Radiation Oncology, University of Toronto, Toronto, ON, Canada.,Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.,Institute of Medical Science, University of Toronto, Toronto, ON, Canada
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25
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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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Wang Y, Xia W, Liu B, Zhou L, Ni M, Zhang R, Shen J, Bai Y, Weng G, Yuan S, Gao X. Exploration of spatial distribution of brain metastasis from small cell lung cancer and identification of metastatic risk level of brain regions: a multicenter, retrospective study. Cancer Imaging 2021; 21:41. [PMID: 34120659 PMCID: PMC8201893 DOI: 10.1186/s40644-021-00410-w] [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: 03/21/2021] [Accepted: 06/01/2021] [Indexed: 11/23/2022] Open
Abstract
Objectives This study aimed to explore the spatial distribution of brain metastases (BMs) from small cell lung cancer (SCLC) a homogenous sample, and to identify the metastatic risk levels in brain regions. Methods T1-enhanced magnetic resonance imaging (MRI) from SCLC patients were retrospectively reviewed from three medical institutions in China. All images were registered to the standard brain template provided by the Montreal Neurological Institute (MNI) 152 database, followed by transformation of the location of all BMs to the space of standard brain. The MNI structural atlas and Anatomical Automatic Labeling (AAL) atlas were then used to identify the anatomical brain regions, and the observed and expected rates of BMs were compared using 2-tailed proportional hypothesis testing. The locations and sizes of brain lesions were analyzed after image standardization. Results A total of 215 eligible patients with 1033 lesions were screened by MRI, including 157 (73%) males and 58 (27%) females. The incidence of crucial structures were as follows: hippocampus 0.68%, parahippocampal 0.97%, brainstem 2.05%, cauate 0.68%, putamen 0.68%, pallidum 0.2%, thalamus 1.36%. No BMs were found in the amygdala, pituitary gland, or pineal gland. The cumulative frequency of the important structures was 6.62%. Based on the results of MNI structural atlas, the cerebellum, deep white matter and brainstem was identified as a higher risk region than expected for BMs (P = 9.80 ×10−15, 9.04 ×10−6), whereas temporal lobe were low-risk regions (P = 1.65 ×10−4). More detailed AAL atlas revealed that the low-risk regions for BMs was inferior frontal gyrus (P = 6.971 ×10−4), while the high-risk regions for BMs was cerebellar hemispheres (P = 1.177 ×10−9). Conclusion Many crucial structures including the hippocampus, parahippocampus, pituitary gland and thalamus etc. have low frequency of brain metastases in a population of SCLC patients. This study provides the help to investigate the clinical feasibility of HA-WBRT and non-uniform dose of PCI in a population of SCLC patients. Supplementary Information The online version contains supplementary material available at 10.1186/s40644-021-00410-w.
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Affiliation(s)
- Yong Wang
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No.440, Jiyan Road, Jinan, 250117, Shandong, China
| | - Wei Xia
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, 88 Keling Road, Suzhou New District, Suzhou, 215163, Jiangsu, China.,Jinan Guoke Medical Engineering and Technology Development Co., Ltd., Pharmaceutical Valley New Drug Creation Platform, Jinan, Shandong, China
| | - Baoyan Liu
- Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, Shandong, China
| | - Liu Zhou
- Jihua Laboratory, Foshan, Guangdong, China
| | - Meng Ni
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No.440, Jiyan Road, Jinan, 250117, Shandong, China
| | - Rui Zhang
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, 88 Keling Road, Suzhou New District, Suzhou, 215163, Jiangsu, China
| | - Jingyi Shen
- Fudan University Shanghai Cancer Center; Shanghai Medical College, Fudan University, shanghai, China
| | - Yujun Bai
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.,Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No.440, Jiyan Road, Jinan, 250117, Shandong, China
| | | | - Shuanghu Yuan
- Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China. .,Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, No.440, Jiyan Road, Jinan, 250117, Shandong, China.
| | - Xin Gao
- Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, 88 Keling Road, Suzhou New District, Suzhou, 215163, Jiangsu, China. .,Jinan Guoke Medical Engineering and Technology Development Co., Ltd., Pharmaceutical Valley New Drug Creation Platform, Jinan, Shandong, China.
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Zhang Y, Chen YC, Hu L, You J, Gu W, Li Q, Chen H, Mao C, Yin X. Chemotherapy-induced functional changes of the default mode network in patients with lung cancer. Brain Imaging Behav 2021; 14:847-856. [PMID: 30617783 DOI: 10.1007/s11682-018-0030-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
Previous studies have demonstrated that cognitive impairment is associated with neurophysiological changes in lung cancer following chemotherapy. This study aimed to investigate the intrinsic functional connectivity (FC) pattern within the default mode network (DMN) and its associations with cognitive impairment in patients with lung cancer revealed by resting-state functional magnetic resonance imaging (fMRI). Resting-state fMRI scans were acquired from 21 post-chemotherapy and 27 non-chemotherapy lung cancer patients and 30 healthy controls. All groups were age, gender and education-matched. The posterior cingulate cortex (PCC) was chosen as the seed region to detect the FC patterns and then determine whether these changes were related with specific cognitive performance. Compared with non-chemotherapy lung cancer patients, chemotherapy patients revealed decreased FC between the PCC and the right anterior cingulate cortex (ACC), left inferior parietal lobule (IPL), and left medial prefrontal cortex (mPFC), as well as increased FC with the left postcentral gyrus (PoCG). Relative to healthy controls, post-chemotherapy patients exhibited reduced FC between the PCC and the left ACC and left temporal lobe, as well as increased FC with the right PoCG. Moreover, the decreased FC of the PCC to bilateral ACC in post-chemotherapy patients was positively associated with reduced MoCA scores (left: r = 0.529, p = 0.029; right: r = 0.577, p = 0.015). The current study mainly demonstrated reduced resting-state FC pattern within the DMN regions that was linked with impaired cognitive function in lung cancer patients after chemotherapy. These findings illustrated the potential role of the DMN in lung cancer patients that will provide novel insight into the underlying neuropathological mechanisms in chemotherapy-induced cognitive impairment.
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Affiliation(s)
- Yujie Zhang
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University, No.68, Changle Road, Nanjing, 210006, China
| | - Yu-Chen Chen
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University, No.68, Changle Road, Nanjing, 210006, China.
| | - Lanyue Hu
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University, No.68, Changle Road, Nanjing, 210006, China
| | - Jia You
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University, No.68, Changle Road, Nanjing, 210006, China
| | - Wei Gu
- Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Qian Li
- Department of Respiratory Medicine, Nanjing First Hospital, Nanjing Medical University, Nanjing, China
| | - Huiyou Chen
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University, No.68, Changle Road, Nanjing, 210006, China
| | - Cunnan Mao
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University, No.68, Changle Road, Nanjing, 210006, China
| | - Xindao Yin
- Department of Radiology, Nanjing First Hospital, Nanjing Medical University, No.68, Changle Road, Nanjing, 210006, China.
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Abstract
Prophylactic cranial irradiation (PCI) has well established place in therapy for patients with limited-disease small cell lung cancer who responded to treatment. The data from randomized trials document that PCI reduces brain metastases rate from approximately 60% to 30%, and increases 3-year overall survival by approximately 5%. Currently, the dose of 25 Gy in 10 fractions is considered as standard. In attempt to reduce neuropsychological sequelae attributable to PCI hippocampal sparing techniques are employed. The existing studies suggest the benefit of hippocampal sparing in limiting memory and higher neurocognitive function losses, but with a risk of failures in the spared region. Ongoing studies will further validate the role of hippocampal sparing, both in terms of toxicity reduction and metastases prevention. PCI for patients who have undergone resection for stage I small cell lung cancer (SCLC) is not recommended, PCI may be, however, associated with a favourable outcome in SCLC patients who have undergone complete surgery in stages II−III. The role of PCI in extensive-disease (ED) SCLC has been evolving. Most recent evidence indicate that PCI is controversial in ED patients with response to initial chemotherapy and absence of brain metastases confirmed by contrast-enhanced MRI. The patients who do not receive PCI, must, however, receive periodic MRI examination during follow-up, i.e., remain under active surveillance with access to radiotherapy at brain relapse. The assessment of safety and effectiveness of hippocampal-sparing PCI, with or without drug neuroprotection in consideration of diverse combinations of radiotherapy, chemotherapy and immunotherapy create a background for future directions of research.
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Affiliation(s)
- Rafal Suwinski
- Radiotherapy and Chemotherapy Clinic and Teaching Hospital, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Poland
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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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Cifarelli CP, Vargo JA, Fang W, Liscak R, Guseynova K, Warnick RE, Lee CC, Yang HC, Borghei-Razavi H, Maiti T, Siddiqui ZA, Yuan JC, Grills IS, Mathieu D, Touchette CJ, Cordeiro D, Chiang V, Hess J, Tien CJ, Faramand A, Kano H, Barnett GH, Sheehan JP, Lunsford LD. Role of Gamma Knife Radiosurgery in Small Cell Lung Cancer: A Multi-Institutional Retrospective Study of the International Radiosurgery Research Foundation (IRRF). Neurosurgery 2021; 87:664-671. [PMID: 31599324 DOI: 10.1093/neuros/nyz428] [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] [Received: 09/20/2018] [Accepted: 08/04/2019] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Despite a high incidence of brain metastases in patients with small-cell lung cancer (SCLC), limited data exist on the use of stereotactic radiosurgery (SRS), specifically Gamma Knife™ radiosurgery (Elekta AB), for SCLC brain metastases. OBJECTIVE To provide a detailed analysis of SCLC patients treated with SRS, focusing on local failure, distant brain failure, and overall survival (OS). METHODS A multi-institutional retrospective review was performed on 293 patients undergoing SRS for SCLC brain metastases at 10 medical centers from 1991 to 2017. Data collection was performed according to individual institutional review boards, and analyses were performed using binary logistic regression, Cox-proportional hazard models, Kaplan-Meier survival analysis, and competing risks analysis. RESULTS Two hundred thirty-two (79%) patients received SRS as salvage following prior whole-brain irradiation (WBRT) or prophylactic cranial irradiation, with a median marginal dose of 18 Gy. At median follow-up after SRS of 6.4 and 18.0 mo for surviving patients, the 1-yr local failure, distant brain failure, and OS were 31%, 49%, and 28%. The interval between WBRT and SRS was predictive of improved OS for patients receiving SRS more than 1 yr after initial treatment (21%, <1 yr vs 36%, >1 yr, P = .01). On multivariate analysis, older age was the only significant predictor for OS (hazard ratio 1.63, 95% CI 1.16-2.29, P = .005). CONCLUSION SRS plays an important role in the management of brain metastases from SCLC, especially in salvage therapy following WBRT. Ongoing prospective trials will better assess the value of radiosurgery in the primary management of SCLC brain metastases and potentially challenge the standard application of WBRT in SCLC patients.
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Affiliation(s)
- Christopher P Cifarelli
- Department of Neurosurgery, School of Medicine, West Virginia University, Morgantown, West Virginia.,Department of Radiation Oncology, School of Medicine, West Virginia University, Morgantown, West Virginia
| | - John A Vargo
- Department of Neurosurgery, School of Medicine, West Virginia University, Morgantown, West Virginia.,Department of Radiation Oncology, School of Medicine, West Virginia University, Morgantown, West Virginia
| | - Wei Fang
- West Virginia Clinical and Translational Science Institute, School of Medicine, West Virginia University, Morgantown, West Virginia
| | - Roman Liscak
- Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague, Czech Republic
| | - Khumar Guseynova
- Department of Stereotactic and Radiation Neurosurgery, Na Homolce Hospital, Prague, Czech Republic
| | | | - Cheng-Chia Lee
- Department of Neurosurgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Huai-Che Yang
- Department of Neurosurgery, Taipei Veterans General Hospital, Taipei, Taiwan
| | | | - Tonmoy Maiti
- Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio
| | - Zaid A Siddiqui
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan
| | - Justin C Yuan
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan
| | - Inga S Grills
- Department of Radiation Oncology, Beaumont Health System, Royal Oak, Michigan
| | - David Mathieu
- Division of Neurosurgery, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Centre de Recherche du CHUS, Sherbrooke, Canada
| | - Charles J Touchette
- Division of Neurosurgery, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Centre de Recherche du CHUS, Sherbrooke, Canada
| | - Diogo Cordeiro
- Department of Neurosurgery, School of Medicine, University of Virginia, Charlottesville, Virginia
| | - Veronica Chiang
- Department of Neurosurgery, Yale School of Medicine, Yale University, New Haven, Connecticut.,Department of Radiation Oncology, Yale School of Medicine, Yale University, New Haven, Connecticut
| | - Judith Hess
- Department of Neurosurgery, Yale School of Medicine, Yale University, New Haven, Connecticut.,Department of Radiation Oncology, Yale School of Medicine, Yale University, New Haven, Connecticut
| | - Christopher J Tien
- Department of Neurosurgery, Yale School of Medicine, Yale University, New Haven, Connecticut.,Department of Radiation Oncology, Yale School of Medicine, Yale University, New Haven, Connecticut
| | - Andrew Faramand
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Hideyuki Kano
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
| | - Gene H Barnett
- Department of Neurosurgery, Cleveland Clinic, Cleveland, Ohio
| | - Jason P Sheehan
- Department of Neurosurgery, School of Medicine, University of Virginia, Charlottesville, Virginia
| | - L Dade Lunsford
- Department of Neurosurgery, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
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Surgery in Small-Cell Lung Cancer. Cancers (Basel) 2021; 13:cancers13030390. [PMID: 33494285 PMCID: PMC7864514 DOI: 10.3390/cancers13030390] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2020] [Revised: 01/12/2021] [Accepted: 01/18/2021] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Small-cell lung cancer (SCLC) accounts for approximately 15% of all lung cancers and is one of the most aggressive tumors, with poor prognosis and limited therapeutic options. This review summarizes the main results observed with surgery in SCLC, discussing the critical issues related to the use of this approach. Following two old randomized clinical trials showing no benefit with surgery, several prospective, retrospective, and population-based studies have demonstrated the feasibility of a multimodality approach including surgery in addition to chemotherapy and radiotherapy in patients with selected stage I SCLC. Currently, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging within a multimodal approach and after a multidisciplinary evaluation. Abstract Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.
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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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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: 8] [Impact Index Per Article: 1.6] [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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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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Nawrocki S, Sugajska A. Study protocol: watchful observation of patients with limited small cell lung cancer instead of the PCI-prospective, multi-center one-arm study. BMC Cancer 2020; 20:231. [PMID: 32188425 PMCID: PMC7079435 DOI: 10.1186/s12885-020-06721-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Accepted: 03/06/2020] [Indexed: 12/01/2022] Open
Abstract
Background Prophylactic cranial irradiation (PCI) is a current standard of care after confirmed response to radical chemoradiotherapy for limited disease small cell lung cancer (LD-SCLC). This standard is mostly based on results of old randomized studies when brain imaging with magnetic resonance (MRI) was not available. Survival benefit of PCI in extended disease SCLC was recently challenged by the results of randomized phase III study from Japan. Methods Eighty patients with LD-SCLC after response to chest chemoradiotherapy will be enrolled. Patients will be followed up by brain MRI every 3 to 6 months up to 3 years. Neurocognitive function tests will be performed at baseline and after 12 and 24 months. Patients who develop brain metastases will be irradiated with stereotactic (SRT) or whole brain RT (WBRT). The primary endpoint is overall survival. The secondary endpoints are: response rate to radiotherapy of early detected brain metastases, analysis of efficacy of SRT and WBRT; assessment and analysis of neurocognitive functions and QoL in the studied cohorts: QLQ-C30 questionnaire and the California Verbal Learning Test, Color connection test, Benton visual retention test, and verbal fluency test will be carried out. Discussion The results of this trial may contribute to changing of LD-SCLC clinical management by deescalating the treatment. There is a lack of prospective, recent studies in LD-SCLC patients with omission of PCI and modern radiation therapy technologies for developed brain metastases. The comprehensive neurocognitive function testing will help to assess the impact of modern radiotherapy (SRT) compared with WBRT and no-PCI in SCLC patients. A subgroup of long-term survivors, who will not develop brain metastases, will not be exposed to unnecessary brain irradiation with its deleterious consequences. The limitation of our study is a lack of parallel randomized control arm. This is a potential source of bias; however, randomized study will be difficult to complete for two major reasons: (1) limited population of LD-SCLC eligible for the study and (2) opinions of our patients, who after information and discussion about benefits and potential harms of PCI, often choose to omit PCI in our practice. Trial registration ClinicalTrials.gov Identifier: NCT04168281, 19 Nov. 2019.
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Affiliation(s)
- Sergiusz Nawrocki
- Katedra Onkologii, Wydział Lekarski, Collegium Medicum, Uniwersytet Warmińsko-Mazurski w Olsztynie, Olsztyn, Poland.
| | - Anna Sugajska
- Katedra Onkologii, Wydział Lekarski, Collegium Medicum, Uniwersytet Warmińsko-Mazurski w Olsztynie, Olsztyn, Poland
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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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Gaspar LE, Prabhu RS, Hdeib A, McCracken DJ, Lasker GF, McDermott MW, Kalkanis SN, Olson JJ. Congress of Neurological Surgeons Systematic Review and Evidence-Based Guidelines on the Role of Whole Brain Radiation Therapy in Adults With Newly Diagnosed Metastatic Brain Tumors. Neurosurgery 2019; 84:E159-E162. [PMID: 30629211 DOI: 10.1093/neuros/nyy541] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 10/18/2018] [Indexed: 11/13/2022] Open
Abstract
TARGET POPULATION Adult patients (older than 18 yr of age) with newly diagnosed brain metastases. QUESTION If whole brain radiation therapy (WBRT) is used, is there an optimal dose/fractionation schedule? RECOMMENDATIONS Level 1: A standard WBRT dose/fractionation schedule (ie, 30 Gy in 10 fractions or a biological equivalent dose [BED] of 39 Gy10) is recommended as altered dose/fractionation schedules do not result in significant differences in median survival or local control. Level 3: Due to concerns regarding neurocognitive effects, higher dose per fraction schedules (such as 20 Gy in 5 fractions) are recommended only for patients with poor performance status or short predicted survival. Level 3: WBRT can be recommended to improve progression-free survival for patients with more than 4 brain metastases. QUESTION What impact does tumor histopathology or molecular status have on the decision to use WBRT, the dose fractionation scheme to be utilized, and its outcomes? RECOMMENDATIONS There is insufficient evidence to support the choice of any particular dose/fractionation regimen based on histopathology. Molecular status may have an impact on the decision to delay WBRT in subgroups of patients, but there is not sufficient data to make a more definitive recommendation. QUESTION Separate from survival outcomes, what are the neurocognitive consequences of WBRT, and what steps can be taken to minimize them? RECOMMENDATIONS Level 2: Due to neurocognitive toxicity, local therapy (surgery or SRS) without WBRT is recommended for patients with ≤4 brain metastases amenable to local therapy in terms of size and location. Level 2: Given the association of neurocognitive toxicity with increasing total dose and dose per fraction of WBRT, WBRT doses exceeding 30 Gy given in 10 fractions, or similar biologically equivalent doses, are not recommended, except in patients with poor performance status or short predicted survival. Level 2: If prophylactic cranial irradiation (PCI) is given to prevent brain metastases for small cell lung cancer, the recommended WBRT dose/fractionation regimen is 25 Gy in 10 fractions, and because this can be associated with neurocognitive decline, patients should be told of this risk at the same time they are counseled about the possible survival benefits. Level 3: Patients having WBRT (given for either existing brain metastases or as PCI) should be offered 6 mo of memantine to potentially delay, lessen, or prevent the associated neurocognitive toxicity. QUESTION Does the addition of WBRT after surgical resection or radiosurgery improve progression-free or overall survival outcomes when compared to surgical resection or radiosurgery alone? RECOMMENDATIONS Level 2: WBRT is not recommended in WHO performance status 0 to 2 patients with up to 4 brain metastases because, compared to surgical resection or radiosurgery alone, the addition of WBRT improves intracranial progression-free survival but not overall survival. Level 2: In WHO performance status 0 to 2 patients with up to 4 brain metastases where the goal is minimizing neurocognitive toxicity, as opposed to maximizing progression-free survival and overall survival, local therapy (surgery or radiosurgery) without WBRT is recommended. Level 3: Compared to surgical resection or radiosurgery alone, the addition of WBRT is not recommended for patients with more than 4 brain metastases unless the metastases' volume exceeds 7 cc, or there are more than 15 metastases, or the size or location of the metastases are not amenable to surgical resection or radiosurgery.The full guideline can be found at: https://www.cns.org/guidelines/guidelines-treatment-adults-metastatic-brain-tumors/chapter_3.
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Affiliation(s)
- Laurie E Gaspar
- Department of Radiation Oncology, University of Colorado Denver School of Medicine, Aurora, Colorado
| | - Roshan S Prabhu
- Southeast Radiation Oncology Group and Levine Cancer Institute, Atrium Health, Charlotte, North Carolina
| | - Alia Hdeib
- Department of Neurosurgery, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio
| | - D Jay McCracken
- Department of Neurosurgery, Emory University, Atlanta, Georgia
| | - George F Lasker
- Departments of Neurological Surgery, Radiation Oncology, Otolaryngology, University of California San Francisco, San Francisco, California
| | - Michael W McDermott
- Departments of Neurological Surgery, Radiation Oncology, Otolaryngology, University of California San Francisco, San Francisco, California
| | - Steven N Kalkanis
- Department of Neurosurgery, Henry Ford Health System, Detroit, Michigan
| | - Jeffrey J Olson
- Department of Neurosurgery, Emory University, Atlanta, Georgia
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Koh M, Song SY, Jo JH, Park G, Park JW, Kim SS, Choi EK. The value of prophylactic cranial irradiation in limited-stage small cell lung cancer: should it always be recommended? Radiat Oncol J 2019; 37:156-165. [PMID: 31591863 PMCID: PMC6790796 DOI: 10.3857/roj.2019.00318] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Accepted: 07/22/2019] [Indexed: 12/12/2022] Open
Abstract
Purpose Prophylactic cranial irradiation (PCI) is a standard treatment for limited-stage small cell lung cancer (LS-SCLC) showing a response to initial treatment, but many patients do not receive PCI due to comorbidities or refusal. This study aims to define the patient group for whom PCI can be omitted with minimal risk. Materials and Methods Patients with LS-SCLC who underwent radiotherapy with curative aim at our institution between January 2004 and December 2015 were retrospectively reviewed. Patients who did not receive PCI were evaluated for brain metastasis-free survival (BMFS), progression-free survival (PFS), overall survival (OS), and prognostic factors for survival, and treatment outcomes were compared with a patient cohort who received PCI. Results A total of 350 patients achieved a response following thoracic radiotherapy, and 190 of these patients did not receive PCI. Stage I–II and a complete response (CR) to initial therapy were good prognostic factors for BMFS and OS on univariate analysis. Patients with both stage I–II and a CR who declined PCI showed comparable 2-year BMFS to those who received PCI (92% vs. 89%). In patients who achieved CR, PCI did not significantly improve OS or PFS. Conclusion There should be less concern about omitting PCI in patients with comorbidities if they have stage I–II or a CR, with brain metastasis control being comparable to those patients who receive PCI.
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Affiliation(s)
- Minji Koh
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Si Yeol Song
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji Hwan Jo
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Geumju Park
- Department of Radiation Oncology, Inje University Haeundae Paik Hospital, Busan, Korea
| | - Jae Won Park
- Department of Radiation Oncology, Yeungnam University Medical Center, Daegu, Korea
| | - Su Ssan Kim
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Eun Kyung Choi
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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40
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Chu X, Li S, Xia B, Chu L, Yang X, Ni J, Zou L, Li Y, Xie C, Lin J, Zhu Z. Patterns of brain metastasis immediately before prophylactic cranial irradiation (PCI): implications for PCI optimization in limited-stage small cell lung cancer. Radiat Oncol 2019; 14:171. [PMID: 31533763 PMCID: PMC6749639 DOI: 10.1186/s13014-019-1371-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 08/28/2019] [Indexed: 12/12/2022] Open
Abstract
Background Prophylactic cranial irradiation (PCI) is indicated for limited-stage small cell lung cancer (LS-SCLC) with good response to chemoradiotherapy (CRT). However, brain metastasis (BM) developed in LS-SCLC before PCI is not rare. In this study, we comprehensively investigated the features of pre-PCI BMs, aiming to explore the potential of PCI optimization for LS-SCLC. Methods One-hundred-ten LS-SCLC patients achieving clinical complete remission after definitive CRT with contrast-enhanced cranial magnetic resonance imaging (MRI) at baseline and immediately before PCI were included. The time trend and risk factors for pre-PCI BM were evaluated. Several radiological features, including numbers, sizes, and locations of pre-PCI BMs, were investigated to explore the technical feasibility of stereotactic radiotherapy and hippocampal-avoidance (HA) PCI. Results Twenty-four (21.8%) of the LS-SCLC patients harbored pre-PCI BM, all except one were asymptomatic. CRT duration (CRT-D) was the only independent risk factor for pre-PCI BM. The pre-PCI BM rate gradually increased in line with a growing time interval between treatment initiation and pre-PCI MRI. Pre-PCI BM and prolonged CRT-D were both correlated with worse overall survival. Of 129 pre-PCI intracranial lesions, 2 (1.5%) were in the HA region. Eight of the 24 (33.3%) pre-PCI BM patients were ineligible for stereotactic radiotherapy. Conclusion Our findings suggest that PCI is still of importance in LS-SCLC, and MRI evaluation before PCI is indispensable. Investigations are warranted to explore the possibility of moving PCI up to before CRT completion in LS-SCLC patients with prolonged CRT-D. HA-PCI could be considered to reduce neurotoxicity. Electronic supplementary material The online version of this article (10.1186/s13014-019-1371-4) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Xiao Chu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Shuyan Li
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Bingqing Xia
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.,Department of Radiology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, 200032, China
| | - Li Chu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Xi Yang
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Jianjiao Ni
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Liqing Zou
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Yida Li
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China.,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China
| | - Congying Xie
- Radiotherapy and Chemotherapy Department, the 1st Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China
| | - Jie Lin
- Department of Medical Oncology, the Second Affiliated Hospital of Kunming Medical University, 374 Dianmian Avenue, Wuhua District, Kunming, 650101, Yunnan, China.
| | - Zhengfei Zhu
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Fudan University, 270 DongAn Road, XuHui District, Shanghai, 200032, China. .,Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
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Nesbit EG, Leal TA, Kruser TJ. What is the role of radiotherapy for extensive-stage small cell lung cancer in the immunotherapy era? Transl Lung Cancer Res 2019; 8:S153-S162. [PMID: 31673520 DOI: 10.21037/tlcr.2019.05.01] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Small cell lung cancer has been a difficult disease to treat with poor survival and few significant improvements in outcomes in the last three decades. Most recently the addition of atezolizumab to chemotherapy in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC) resulted in improved overall survival and progression-free survival compared to chemotherapy alone. Recent randomized studies examining both consolidative thoracic radiotherapy and prophylactic cranial irradiation (PCI) in ES-SCLC have impacted the utilization of these interventions. The approval of immune checkpoint inhibitors (ICIs) to platinum/etoposide chemotherapy for the treatment of ES-SCLC in the front-line setting may also further impact the role of radiotherapy in this disease. In this article, we review the current evidence supporting thoracic radiotherapy in ES-SCLC and discuss the promising therapeutic implications of thoracic radiation in light of the inclusion of ICIs. We also address how the increasing routine use of surveillance brain magnetic resonance imaging (MRI) and ICIs may diminish the use of PCI in ES-SCLC.
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Affiliation(s)
- Eric G Nesbit
- Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
| | - Ticiana A Leal
- Division of Hematology & Oncology, University of Wisconsin Carbone Cancer Center, Madison, WI, USA
| | - Tim J Kruser
- Department of Radiation Oncology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA
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Limited-Stage Small Cell Lung Cancer: Is Prophylactic Cranial Irradiation Necessary? Pract Radiat Oncol 2019; 9:e599-e607. [PMID: 31271904 DOI: 10.1016/j.prro.2019.06.014] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2019] [Revised: 06/14/2019] [Accepted: 06/17/2019] [Indexed: 12/12/2022]
Abstract
PURPOSE Prophylactic cranial irradiation (PCI) reduces the incidence of brain metastases in patients with limited stage small cell lung cancer (LS-SCLC). However, PCI is associated with neurotoxicity. Previous studies have not consistently used pretreatment magnetic resonance imaging. Modern imaging improvements continue to enhance early metastasis detection, potentially decreasing the utility of PCI. We sought to determine whether PCI was associated with improved outcomes in LS-SCLC patients with modern imaging. METHODS AND MATERIALS We identified LS-SCLC patients with no intracranial disease who were treated between 2007 and 2018. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated and multivariate Cox proportional hazards models were generated. The cumulative incidence of brain metastases was estimated using competing risks methodology. RESULTS Ninety-two patients were identified without intracranial disease at initial staging, 39 of whom received PCI. Median follow-up was 56.7 months. The median OS for the cohort was 35.5 months (95% CI, 25.8-49.3), and median PFS was 19.1 months (95% CI, 12.3-30.5). Median OS with PCI versus observation was 37.9 months (95% CI, 31.8-not reached) versus 30.5 months (95% CI, 14.6-56.1; P = .07), whereas median PFS was 26.3 months (95% CI 19.1-not reached) versus 12.3 months (95% CI, 8.5-30.5; P = .02), respectively. Overall, at 2 years, the cumulative incidence of brain metastases was 10% with PCI and 29% without; this increased to 32% and 29% by 4 years (P = .66). In those patients who had negative magnetic resonance imaging of the brain after completing initial treatment, the 1-year cumulative incidence of brain metastasis was not significantly different at 8% versus 11% (P = .46) respectively. Both PCI and treatment response were independent predictors for PFS on multivariate analysis. Stratified by disease response, patients with a complete response did not benefit from PCI (P = .50), whereas those with partial response or stable disease experienced improved PFS (P = .01). CONCLUSIONS Overall, PCI was associated with improved PFS and reduced early incidence of brain metastases. Patients achieving a complete response to initial therapy did not experience a PFS benefit with PCI. This may indicate that subsets of LS-SCLC patients can potentially be spared from PCI in the era of modern imaging.
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43
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Faramand A, Niranjan A, Kano H, Flickinger J, Lunsford LD. Primary or salvage stereotactic radiosurgery for brain metastatic small cell lung cancer. J Neurooncol 2019; 144:217-225. [PMID: 31230250 DOI: 10.1007/s11060-019-03224-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Accepted: 06/16/2019] [Indexed: 01/30/2023]
Abstract
PURPOSE We evaluated the outcomes after stereotactic radiosurgery (SRS) for patients who developed new or progressive brain disease regardless of whether they had no prior radiation, PCI, or WBRT. METHODS We retrospectively identified 90 SCLC patients who had SRS between 1991 and 2018. Thirty-one patients had no evidence of brain disease at the time of initial diagnosis but received prophylactic cranial irradiation. Twenty-six without initial brain disease underwent delayed SRS after brain disease was identified. Seventeen patients with synchronous systemic and brain disease underwent WBRT at the time of diagnosis. Fifteen patients had brain disease detected at the time of initial diagnosis and had initial SRS. RESULTS We found no difference in overall survival between patients who received initial PCI or WBRT compared to patients treated with SRS alone at the time when brain metastases were identified. PCI was not associated with a longer duration between initial diagnosis and the development of brain metastasis. Local tumor control was achieved in 49 out of 58 patients who had follow up MRI available for review (84.5%). Actuarial local tumor control at 3, 6, and 12 months was calculated as 92%, 85%, and 80%, respectively. Radiation therapy (PCI or WBRT) before SRS was not associated with better or worse local tumor control. CONCLUSION In this experience neither prior PCI nor WBRT improved survival or local tumor control in SCLC patients who underwent SRS for new or recurrent brain disease.
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Affiliation(s)
- Andrew Faramand
- Department of Neurosurgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA.
- Department of Neurological Surgery, University of Pittsburgh, Suit B-400, UPMC Presbyterian, 200 Lothrop St, Pittsburgh, PA, 15213, USA.
| | - Ajay Niranjan
- Department of Neurosurgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA
| | - Hideyuki Kano
- Department of Neurosurgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA
| | - John Flickinger
- Department of Neurosurgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA
| | - L Dade Lunsford
- Department of Neurosurgery and Radiation Oncology, University of Pittsburgh Medical Center, Pittsburgh, USA
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44
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Jiang W, Haque W, Verma V, Butler B, Teh BS. Stereotactic radiosurgery for brain metastases from newly diagnosed small cell lung cancer: practice patterns and outcomes. Acta Oncol 2019; 58:491-498. [PMID: 30676131 DOI: 10.1080/0284186x.2018.1562207] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND Up-front stereotactic radiosurgery (SRS) has been historically thought of as inadequate for brain metastases (BM) from newly diagnosed small cell lung cancer (SCLC). This study evaluates national practice patterns and clinical outcomes for BM from SCLC. MATERIAL AND METHODS The National Cancer Database was queried (2004-2013) for patients with newly diagnosed metastatic SCLC receiving intracranial radiotherapy. Patients were grouped into three categories: upfront SRS, whole-brain radiotherapy (WBRT) alone, or WBRT with boost (SRS or fractionated radiotherapy). Statistics included temporal trend assessment by annual percent change (APC), logistic regression, exploratory Kaplan-Meier overall survival (OS) analysis without and with propensity matching, and Cox proportional hazards modeling. RESULTS A total of 14,722 patients met selection criteria, of whom 487 (3.3%), 13,657 (92.8%), and 578 (3.9%) received upfront SRS, WBRT and WBRT with boost, respectively. Utilization of SRS showed a slight increasing trend from 2004 to 2013 (2.7-4.3%). In addition to socioeconomic factors, other variables associated with SRS use included diagnosis after 2010, treatment at academic centers, and residing in higher-educated regions. SRS was less often delivered to patients with node-positive disease (p < .05). On exploratory analysis, SRS cohort was observed to have a higher overall survival (OS) than WBRT-based groups (p < .001), namely in patients without extracranial metastases. CONCLUSIONS Utilization of up-front SRS for SCLC BM has been increasing over time but is driven by socioeconomic disparities. Although there are likely numerous biases associated with the OS findings herein, further research is needed to validate this finding as well as the role of SRS on patients with brain metastases due to SCLC.
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Affiliation(s)
- Wei Jiang
- Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA
- Department of Radiation Oncology, National Cancer Center/Cancer Hospital & Shenzhen Hospital Chinese Academy of Medical Sciences, Shenzhen, China
| | - Waqar Haque
- Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA
| | - Vivek Verma
- Department of Radiation Oncology, Allegheny General Hospital, Pittsburgh, PA, USA
| | - Brian Butler
- Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA
| | - Bin S. Teh
- Department of Radiation Oncology, Houston Methodist Hospital, Houston, TX, USA
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Resio BJ, Hoag J, Chiu A, Monsalve A, Dhanasopon AP, Boffa DJ, Blasberg JD. Prophylactic cranial irradiation is associated with improved survival following resection for limited stage small cell lung cancer. J Thorac Dis 2019; 11:811-818. [PMID: 31019769 DOI: 10.21037/jtd.2019.01.64] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022]
Abstract
Background Brain metastases are a major cause of mortality in patients with small cell lung cancer (SCLC). Prophylactic cranial irradiation (PCI) may improve survival among patients that respond to chemotherapy. Less is known about the outcomes of PCI following surgical resection of SCLC. The purpose of this study was to determine if patients who underwent initial surgical resection of SCLC benefit from PCI. Methods Adult patients in the National Cancer Database (NCDB) who underwent complete resection for primary, non-metastatic SCLC between 2004 and 2015 were identified. Patients that received preoperative chemotherapy or who did not receive appropriate adjuvant chemotherapy were excluded. Patients were grouped by treatment with or without cranial radiation within 8 months of resection. Survival was estimated using Kaplan-Meier and Cox multivariable analysis, adjusting for patient and tumor characteristics. Results A total of 859 patients met inclusion criteria (202 received PCI and 657 did not). Kaplan-Meier analysis demonstrated that patients treated with PCI had significantly improved survival compared to no PCI (5-year survival 59% vs. 50%, logrank P=0.0038). Multivariable cox models confirmed a significantly decreased hazard of death for patients receiving PCI (HR: 0.70, 95% CI: 0.55-0.89, P=0.003). In subset analyses, PCI was associated with significantly improved survival for node positive patients, but not node negative patients. Conclusions PCI is associated with increased survival for patients following surgical resection of SCLC. Patients with positive lymph nodes appear to benefit the most, while it remains unclear if patients with negative lymph nodes derive a benefit. Further study is warranted to clarify which subsets of patients should be treated with PCI.
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Affiliation(s)
- Benjamin J Resio
- Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT 06520-8062, USA
| | - Jessica Hoag
- Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT 06520-8062, USA
| | - Alexander Chiu
- Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT 06520-8062, USA
| | - Andres Monsalve
- Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT 06520-8062, USA
| | - Andrew P Dhanasopon
- Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT 06520-8062, USA
| | - Daniel J Boffa
- Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT 06520-8062, USA
| | - Justin D Blasberg
- Section of Thoracic Surgery, Department of Surgery, Yale School of Medicine, New Haven, CT 06520-8062, USA
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Sarkaria JN, Hu LS, Parney IF, Pafundi DH, Brinkmann DH, Laack NN, Giannini C, Burns TC, Kizilbash SH, Laramy JK, Swanson KR, Kaufmann TJ, Brown PD, Agar NYR, Galanis E, Buckner JC, Elmquist WF. Is the blood-brain barrier really disrupted in all glioblastomas? A critical assessment of existing clinical data. Neuro Oncol 2019; 20:184-191. [PMID: 29016900 DOI: 10.1093/neuonc/nox175] [Citation(s) in RCA: 458] [Impact Index Per Article: 76.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
The blood-brain barrier (BBB) excludes the vast majority of cancer therapeutics from normal brain. However, the importance of the BBB in limiting drug delivery and efficacy is controversial in high-grade brain tumors, such as glioblastoma (GBM). The accumulation of normally brain impenetrant radiographic contrast material in essentially all GBM has popularized a belief that the BBB is uniformly disrupted in all GBM patients so that consideration of drug distribution across the BBB is not relevant in designing therapies for GBM. However, contrary to this view, overwhelming clinical evidence demonstrates that there is also a clinically significant tumor burden with an intact BBB in all GBM, and there is little doubt that drugs with poor BBB permeability do not provide therapeutically effective drug exposures to this fraction of tumor cells. This review provides an overview of the clinical literature to support a central hypothesis: that all GBM patients have tumor regions with an intact BBB, and cure for GBM will only be possible if these regions of tumor are adequately treated.
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Affiliation(s)
- Jann N Sarkaria
- Mayo Clinic, Rochester, Minnesota (J.N.S., I.F.P., D.H.P., D.H.B., N.N.L., C.G., T.C.B., S.H.K., T.J.K., P.D.B., E.G., J.C.B.)
| | - Leland S Hu
- Mayo Clinic, Scottsdale, Arizona (L.S.H., K.R.S.)
| | - Ian F Parney
- Mayo Clinic, Rochester, Minnesota (J.N.S., I.F.P., D.H.P., D.H.B., N.N.L., C.G., T.C.B., S.H.K., T.J.K., P.D.B., E.G., J.C.B.)
| | - Deanna H Pafundi
- Mayo Clinic, Rochester, Minnesota (J.N.S., I.F.P., D.H.P., D.H.B., N.N.L., C.G., T.C.B., S.H.K., T.J.K., P.D.B., E.G., J.C.B.)
| | - Debra H Brinkmann
- Mayo Clinic, Rochester, Minnesota (J.N.S., I.F.P., D.H.P., D.H.B., N.N.L., C.G., T.C.B., S.H.K., T.J.K., P.D.B., E.G., J.C.B.)
| | - Nadia N Laack
- Mayo Clinic, Rochester, Minnesota (J.N.S., I.F.P., D.H.P., D.H.B., N.N.L., C.G., T.C.B., S.H.K., T.J.K., P.D.B., E.G., J.C.B.)
| | - Caterina Giannini
- Mayo Clinic, Rochester, Minnesota (J.N.S., I.F.P., D.H.P., D.H.B., N.N.L., C.G., T.C.B., S.H.K., T.J.K., P.D.B., E.G., J.C.B.)
| | - Terence C Burns
- Mayo Clinic, Rochester, Minnesota (J.N.S., I.F.P., D.H.P., D.H.B., N.N.L., C.G., T.C.B., S.H.K., T.J.K., P.D.B., E.G., J.C.B.)
| | - Sani H Kizilbash
- Mayo Clinic, Rochester, Minnesota (J.N.S., I.F.P., D.H.P., D.H.B., N.N.L., C.G., T.C.B., S.H.K., T.J.K., P.D.B., E.G., J.C.B.)
| | - Janice K Laramy
- University of Minnesota, Minneapolis, Minnesota (J.K.L., W.F.E.)
| | | | - Timothy J Kaufmann
- Mayo Clinic, Rochester, Minnesota (J.N.S., I.F.P., D.H.P., D.H.B., N.N.L., C.G., T.C.B., S.H.K., T.J.K., P.D.B., E.G., J.C.B.)
| | - Paul D Brown
- Mayo Clinic, Rochester, Minnesota (J.N.S., I.F.P., D.H.P., D.H.B., N.N.L., C.G., T.C.B., S.H.K., T.J.K., P.D.B., E.G., J.C.B.)
| | | | - Evanthia Galanis
- Mayo Clinic, Rochester, Minnesota (J.N.S., I.F.P., D.H.P., D.H.B., N.N.L., C.G., T.C.B., S.H.K., T.J.K., P.D.B., E.G., J.C.B.)
| | - Jan C Buckner
- Mayo Clinic, Rochester, Minnesota (J.N.S., I.F.P., D.H.P., D.H.B., N.N.L., C.G., T.C.B., S.H.K., T.J.K., P.D.B., E.G., J.C.B.)
| | - William F Elmquist
- Mayo Clinic, Rochester, Minnesota (J.N.S., I.F.P., D.H.P., D.H.B., N.N.L., C.G., T.C.B., S.H.K., T.J.K., P.D.B., E.G., J.C.B.)
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Yin X, Yan D, Qiu M, Huang L, Yan SX. Prophylactic cranial irradiation in small cell lung cancer: a systematic review and meta-analysis. BMC Cancer 2019; 19:95. [PMID: 30665432 PMCID: PMC6341615 DOI: 10.1186/s12885-018-5251-3] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2018] [Accepted: 12/26/2018] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The efficacy of prophylactic cranial irradiation (PCI) in treating patients with small cell lung cancer (SCLC) has not been clear, and recent randomized studies have demonstrated conflicting results from previously published findings. The purpose of this study was to reevaluate the efficacy of PCI in patients with SCLC and to assess factors associated with its efficacy. METHODS We conducted a quantitative meta-analysis to explore the efficacy of PCI in patients with SCLC. A literature search was performed using EMBASE, MEDLINE, Cochrane and ClinicalTrials.gov databases. We pooled the data and compared overall survival (OS) and brain metastasis (BM) between patients treated with PCI (PCI group) and patients without PCI treatment (observation group). RESULTS Of the 1074 studies identified in our analysis, we selected seven studies including 2114 patients for the current meta-analysis. Our results showed that the PCI group showed decreased BM (HR = 0.45, 95% CI: 0.38-0.55, P < 0.001) and prolonged OS (HR = 0.81, 95% CI: 0.67-0.99, P < 0.001). However, in terms of OS, the pooled analysis showed a high heterogeneity (I2 = 74.1%, P = 0.001). In subgroup analyses of OS, we found that the heterogeneity mainly came from patients with brain imaging after initial chemoradiotherapy (HR = 0.94, 95% CI: 0.74-1.18, P = 0.59). CONCLUSIONS The results of this study showed that PCI has a significant effect on decreasing BM but little benefit in prolonging OS when brain imaging was introduced to confirm lack of BM after initial chemoradiotherapy and before irradiation.
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Affiliation(s)
- Xin Yin
- Department of Radiation Oncology, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, People's Republic of China
| | - Danfang Yan
- Department of Radiation Oncology, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, People's Republic of China
| | - Miao Qiu
- Department of Radiation Oncology, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, People's Republic of China
| | - Liming Huang
- The First Department of Chemotherapy, The First Affiliated Hospital, Fujian Medical University, Fuzhou, Fujian, 350005, People's Republic of China
| | - Sen-Xiang Yan
- Department of Radiation Oncology, the First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, People's Republic of China.
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48
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Morgan TN, Turner RM, Baptiste J, Lyon TD, Maranchie JK, Hrebinko RL, Davies BJ, Gingrich JR, Jacobs BL. Small cell bladder cancer: should we consider prophylactic cranial irradiation? Int Braz J Urol 2018; 45:299-305. [PMID: 30521161 PMCID: PMC6541124 DOI: 10.1590/s1677-5538.ibju.2018.0242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Accepted: 09/29/2018] [Indexed: 11/22/2022] Open
Abstract
Purpose: To describe the clinical characteristics, treatment patterns, and outcomes in patients with small cell bladder cancer at our institution, including those who received prophylactic cranial irradiation (PCI) for the prevention of intracranial recurrence. Materials and Methods: Patients with small cell bladder cancer treated at a single institution between January 1990 and August 2015 were identified and analyzed retrospectively for demographics, tumor stage, treatment, and overall survival. Results: Of 44 patients diagnosed with small cell bladder cancer, 11 (25%) had metastatic disease at the time of presentation. Treatment included systemic chemotherapy (70%), radical surgery (59%), and local radiation (39%). Six patients (14%) received PCI. Median overall survival was 10 months (IQR 4 – 41). Patients with extensive disease had worse overall survival than those with organ confined disease (8 months vs. 36 months, respectively, p = 0.04). Among those who received PCI, 33% achieved 5 - year survival. Conclusion: Outcomes for patients with small cell bladder cancer remain poor. Further research is indicated to determine if PCI increases overall survival in small call bladder cancer patients, especially those with extensive disease who respond to chemotherapy.
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Affiliation(s)
| | - Robert M Turner
- Department of Urology, University of Pittsburgh, Pennsylvania, U.S.A
| | - Julian Baptiste
- School of Medicine, University of Pittsburgh, Pennsylvania, U.S.A
| | - Timothy D Lyon
- Department of Urology, University of Pittsburgh, Pennsylvania, U.S.A
| | - Jodi K Maranchie
- Department of Urology, University of Pittsburgh, Pennsylvania, U.S.A
| | - Ronald L Hrebinko
- Department of Urology, University of Pittsburgh, Pennsylvania, U.S.A
| | - Benjamin J Davies
- Department of Urology, University of Pittsburgh, Pennsylvania, U.S.A
| | | | - Bruce L Jacobs
- Department of Urology, University of Pittsburgh, Pennsylvania, U.S.A
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Abstract
The incidence of brain metastases is projected to rise because survival rates of lung cancer, breast cancer, and melanoma continue to improve (1). The brain is being identified as a sanctuary site for harboring metastases despite excellent control of extracranial disease. This is thought to occur because the drug therapies that control extracranial disease have limited central nervous system (CNS) penetration. The development of brain metastases is a devastating diagnosis affecting both quality of life (QOL) and survival. Symptoms after diagnosis can include headache, nausea, vomiting, seizure, neurocognitive decline, and focal neurologic deficit. Some of these symptoms can be irreversible even after successful treatment of intracranial disease. Treatment of brain metastases often necessitates surgery and radiation. There have been some reports of systemic therapies offering an intracranial response however long-term data is lacking. These treatments for CNS metastases can also lead to neurocognitive sequelae impacting quality of life. Therefore, preventing disease from spreading to the brain is a topic that has generated much interest in oncology. Prophylactic cranial Irradiation (PCI) has been used in leukemia, small cell lung cancer (SCLC), and non-small cell lung cancer (NSCLC). While showing effectiveness in preventing intracranial disease development, its carries with it side effects of neurocognitive decline that can affect QOL. There are Clinical trials exploring novel delivery of PCI and concurrent neuroprotective drug therapy to try to mitigate these neurocognitive sequelae. These will be important trials to complete, as PCI has shown promise in controlling disease and prolonging survival in select patient populations. There are also drug therapies that have shown efficacy in preventing CNS metastases development. This review will explore the current therapies available to prevent CNS metastases.
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Affiliation(s)
- Joseph A Bovi
- Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, United States
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50
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Risk factors for brain metastasis in patients with small cell lung cancer without prophylactic cranial irradiation. Strahlenther Onkol 2018; 194:1152-1162. [DOI: 10.1007/s00066-018-1362-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2018] [Accepted: 08/20/2018] [Indexed: 11/25/2022]
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