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Zhong X, Liu Y, Ji Y, Wang L. Thoracic radiotherapy schedules in limited-stage small cell lung cancer: A systematic review and network meta-analysis. Radiother Oncol 2025; 207:110888. [PMID: 40209857 DOI: 10.1016/j.radonc.2025.110888] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2024] [Revised: 04/01/2025] [Accepted: 04/07/2025] [Indexed: 04/12/2025]
Abstract
BACKGROUND Currently, the accepted standard management of limited-stage small cell lung cancer (LS-SCLC) is concurrent chemoradiotherapy; however, the thoracic radiotherapy regimen remains controversial. Therefore, this meta-analysis aims to compare efficacy and safety of different thoracic radiotherapy regimens. METHODS Relevant randomized controlled trials (RCTs) were sourced in PubMed, Cochrane Library, Web of Science, and EMBASE to assess antitumor effects (overall survival, OS; progression-free survival, PFS; overall response rate, ORR) and toxicity (adverse effects, AEs). RESULTS Of the 2225 screened articles, 8 RCTs (involving 2363 patients) were included. The control arm was defined as 45 Gy/30f BID. The experimental arms were categorized into three groups: high-dose hyper-fractionation (hHyper-RT: 54 Gy/30f BID, 60 Gy/40f BID), hypo-fractionation (Hypo-RT: 42 Gy/15f QD, 65 Gy/26f QD), and conventional fractionation (Conv-RT: 45 Gy/25f QD, 66 Gy/33f QD, 70 Gy/35f QD). Compared with 45 Gy/30f BID, hHyper-RT (54 Gy/30f BID and 60 Gy/40f BID) showed improved OS (HR = 0.55, 95 % CI: 0.37---0.82; HR = 0.69, 95 % CI: 0.48---0.99), hHyper-RT (54 Gy/30f BID) and Hypo-RT (65 Gy/26f QD) improved PFS (HR = 0.70, 95 % CI: 0.49---0.99; HR = 0.78, 95 % CI: 0.62---0.98), whereas OS and PFS with Conv-RT was comparable to that of 45 Gy/30f BID. AE development was comparable among 45 Gy/30f, hHyper-RT, and Hypo-RT, whereas Conv-RT (45 Gy/25f QD) reduces the risk of esophagitis and grade 3-5 esophagitis (RR = 0.70, 95 % CI: 0.58-0.85; RR = 0.50, 95 % CI: 0.35-0.72). No significant difference was found for ORR, pneumonitis or grade 3-5 pneumonitis between the study arms. CONCLUSIONS Compared with 45 Gy/30f BID, hHyper-RT (54 Gy/30f BID and 60 Gy/40f BID) improved OS, while hHyper-RT (54 Gy/30f BID) and Hypo-RT (65 Gy/26f QD) prolonged PFS in LS-SCLC patients, with accepted toxicity.
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Affiliation(s)
- Xiao Zhong
- Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Yingnan Liu
- Shandong University Cancer Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Yuhan Ji
- Shandong First Medical University, Shandong Academy of Medical Sciences, Jinan, Shandong, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Linlin Wang
- Shandong University Cancer Center, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China; Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China.
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Wu Y, Deng L, Wang J, Zhang T, Cao J, Zhou X, Duan J, Bi N. Single-arm phase II study of consolidation serplulimab following hypofractionated radiotherapy with concurrent chemotherapy for patients with limited stage small-cell lung cancer: ASTRUM-LC01 study protocol. BMJ Open 2025; 15:e085552. [PMID: 40398957 PMCID: PMC12096970 DOI: 10.1136/bmjopen-2024-085552] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/20/2024] [Accepted: 04/30/2025] [Indexed: 05/23/2025] Open
Abstract
INTRODUCTION With the inspiring results of the PACIFIC trial in non-small-cell lung cancer (NSCLC), and the CAPIAN and IMpower133 trials in extensive-stage small-cell lung cancer (SCLC), immunotherapy has increasingly gained attention. Serplulimab, a PD-1 inhibitor, showed great antitumour activity in the ASTRUM-005 trial and has been recommended as first-line therapy in extensive-stage SCLC. Whether serplulimab following hypofractionation radiotherapy and chemotherapy could bring better outcomes in limited-stage SCLC remains to be answered. METHODS AND ANALYSIS We designed a prospective multicentre single-arm phase II clinical trial to evaluate both the efficacy and safety of chemoradiotherapy and consolidation by serplulimab in limited-stage SCLC. Eligible patients will receive standard chemotherapy for four cycles and concurrent thoracic radiotherapy with a total dose of 45 Gy in 3 weeks and a 3 Gy dose per fraction. Prophylactic cranial irradiation is recommended for responding patients. Serplulimab will be delivered afterwards every 3 weeks for up to 1 year. Based on sample size estimation, 55 patients will be enrolled in total. ETHICS AND DISSEMINATION Ethics approval was obtained from the Independent Ethics Committee of National Cancer Centre/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College (22/236-3438). TRIAL REGISTRATION NUMBER NCT05443646.
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Affiliation(s)
- Yuqi Wu
- Department of Radiation Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China
| | - Lei Deng
- Department of Radiation Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China
| | - Jianyang Wang
- Department of Radiation Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China
| | - Tao Zhang
- Department of Radiation Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China
| | - Jianzhong Cao
- Department of Radiation Oncology, Shanxi Province Cancer Hospital/Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences, Taiyuan, People's Republic of China
| | - Xiaohong Zhou
- Department of Radiation Oncology, Jiamusi Medical College, Jiamusi, Heilongjiang, China
| | - Jianchun Duan
- Department of Medical Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China
| | - Nan Bi
- Department of Radiation Oncology, Cancer Hospital Chinese Academy of Medical Sciences, Beijing, China
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Grønberg BH, Killingberg KT, Fløtten Ø, Bjaanæs MM, Brustugun OT, Madebo T, Langer SW, Risumlund SL, Schytte T, Helbekkmo N, Neumann K, Yksnøy Ø, Engleson J, Fluge S, Naustdal T, Giske LE, Nyman J, Tsakonas G, Halvorsen TO. High-Dose Versus Standard-Dose Twice-Daily Thoracic Radiotherapy in Limited-Stage SCLC: Final Survival Data, Long-Term Toxicity, and Relapse Patterns in a Randomized, Open-Label, Phase II Trial. J Thorac Oncol 2025:S1556-0864(25)00696-3. [PMID: 40258573 DOI: 10.1016/j.jtho.2025.04.007] [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: 02/14/2025] [Revised: 04/09/2025] [Accepted: 04/14/2025] [Indexed: 04/23/2025]
Abstract
INTRODUCTION Chemoradiotherapy is standard treatment for limited-stage SCLC. However, most patients relapse and there is a need for better treatment. We investigated whether twice-daily thoracic radiotherapy (TRT) of 60 Gy/40 fractions improves survival compared with the established schedule of 45 Gy/30 fractions. Here, we report final survival data and long-term toxicity. METHODS Randomized, open-label, phase II trial. Eligible patients had performance status of 0 to 2, were above or equal to 18 years of age, underwent 18F-fluorodeoxyglucose positron emission tomography computed tomography and brain magnetic resonance imaging for staging, and were randomized 1:1 to TRT of 60 or 45 Gy. Patients were to receive four courses of platinum and etoposide chemotherapy, and responders were offered prophylactic cranial irradiation. RESULTS A total of 170 patients were randomized (60 Gy: n = 89, 45 Gy: n = 81). Median age was 65 years, 31% above or equal to 70 years, 57% women, 89% had performance status of 0 to 1, 83% stage III disease, median planning target volume was 305 cm3, and 67% were treated with three-dimensional conformal radiotherapy. Median overall survival in the 60 Gy group was significantly longer (43.5 versus 22.5 mo, hazard ratio 0.68, 95% confidence interval 0.48-0.98, p = 0.037). The 60 Gy group did not experience more acute grades 3 to 4 esophagitis (60 Gy: 21%, 45 Gy: 18%, p = 0.83) or pneumonitis (60 Gy: 3%, 45 Gy: 0%, p = 0.39). Two patients, both in the 60 Gy group, developed esophageal strictures, whereas 11 patients (60 Gy: n = 5, 45 Gy: n = 6) developed severe long-term eating and swallowing dysfunction. CONCLUSION Twice-daily TRT of 60 Gy/40 fractions was well tolerated and prolonged survival compared with 45 Gy/30 fractions in patients with limited-stage SCLC. This trial is registered at ClinicalTrials.gov: NCT02041845.
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Affiliation(s)
- Bjørn Henning Grønberg
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Oncology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway.
| | - Kristin Toftaker Killingberg
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Oncology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Øystein Fløtten
- Department of Thoracic Medicine, Haukeland University Hospital, Bergen, Norway
| | | | - Odd Terje Brustugun
- Section of Oncology, Drammen Hospital, Vestre Viken HF, Drammen, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway
| | - Tesfaye Madebo
- Department of Pulmonary Medicine, Stavanger University Hospital, Stavanger, Norway
| | - Seppo Wang Langer
- Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Signe Lenora Risumlund
- Department of Oncology, Copenhagen University Hospital - Rigshospitalet, Copenhagen, Denmark
| | - Tine Schytte
- Department of Oncology, Odense University Hospital, Odense, Denmark
| | - Nina Helbekkmo
- Departments of Pulmonology and Oncology, University Hospital of North Norway, Tromsø, Norway
| | - Kirill Neumann
- Department of Pulmonology, Akershus University Hospital, Lørenskog, Norway
| | - Øyvind Yksnøy
- Department of Pulmonology, Ålesund Hospital, Ålesund, Norway
| | - Jens Engleson
- Department of Oncology, Skåne University Hospital, Lund University, Lund, Sweden
| | - Sverre Fluge
- Department of Pulmonology, Haugesund Hospital, Haugesund, Norway
| | | | - Liv Ellen Giske
- Department of Oncology, Innlandet Hospital Trust, Gjøvik, Norway
| | - Jan Nyman
- Department of Oncology, Sahlgrenska University Hospital, Gothenburg, Sweden; Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - Georgios Tsakonas
- Department of Oncology, Karolinska University Hospital, Stockholm, Sweden
| | - Tarje Onsøien Halvorsen
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway; Department of Oncology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
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Videtic GMM. "Timing Is Everything": Reflections on Twice-Daily Radiation Treatment for Small Cell Lung Cancer. JCO Oncol Pract 2025:OP2500166. [PMID: 40198858 DOI: 10.1200/op-25-00166] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2025] [Accepted: 03/10/2025] [Indexed: 04/10/2025] Open
Affiliation(s)
- Gregory M M Videtic
- Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH
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Tsekouras IT, Hotsinpiller WS, Bonner JA, Kole AJ. Facility-Level Disparities in Radiation Use for Limited-Stage Small Cell Lung Cancer. JCO Oncol Pract 2025:OP2400898. [PMID: 39933118 DOI: 10.1200/op-24-00898] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2024] [Revised: 12/15/2024] [Accepted: 01/14/2025] [Indexed: 02/13/2025] Open
Abstract
PURPOSE Treatment of limited-stage small cell lung cancer (LS-SCLC) with twice-a-day radiation therapy (RT) has remained the standard of care for many decades. Growing evidence suggests that outcomes with dose escalated twice-a-day RT may further improve outcomes. However, once-daily treatment remains common. The purpose of this study was to evaluate individual treatment facilities for utilization of twice-a-day RT. METHODS Patients with LS-SCLC treated with definitive chemoradiation from 2004 to 2019 were identified in the National Cancer Database. RT was classified as twice-a-day (45 Gy in 30 fractions) or once-daily (59.4-70.2 Gy in 30-39 fractions). Patients were excluded if surgery was performed. All patients received doublet chemotherapy. Unique treatment facilities delivering at least one twice-a-day treatment course during the study period were classified as BID-treating. Facilities not delivering any twice-a-day RT were classified as QD-only. The proportion of QD-only facilities was identified. Facility-level characteristics associated with QD-only classification were analyzed. RESULTS A total of 22,362 patients with LS-SCLC were treated at 1,222 unique facilities. A slight majority of facilities (n = 644, 52.7%) were BID-treating, whereas fewer (n = 578, 47.3%) were QD-only. A total of 73.9% of academic facilities were BID-treating versus 48.3% of nonacademic facility types (P < .001). Only 20.7% of low volume treatment facilities (lowest quartile of patients with LS-SCLC treated) used twice-a-day fractionation versus 78.2% of the highest quartile volume facilities (P < .001). On multivariable analysis, academic and high-volume facilities were statistically significantly associated with BID-treating classification (adjusted odds ratio, 2.5 [P < .001] and 4.2 [P < .001], respectively). CONCLUSION Nearly half of facilities treating LS-SCLC with definitive chemoradiation do not use twice-a-day fractionation schedules despite ongoing and growing evidence of superiority to once-daily fractionation. High-volume, academic facilities were more likely to offer twice-a-day fractionation.
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Affiliation(s)
- Ian T Tsekouras
- Marnix E. Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL
| | | | - James A Bonner
- Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL
| | - Adam J Kole
- Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, AL
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Levin N, Killingberg KT, Halvorsen TO, Danielsen S, Grønberg BH. Evaluation of Radiation Therapy Treatment Plans in a Randomized Phase 2 Trial Comparing 2 Schedules of Twice-Daily Thoracic Radiation Therapy in Limited Stage Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys 2024; 120:332-342. [PMID: 38583494 DOI: 10.1016/j.ijrobp.2024.03.045] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 03/22/2024] [Accepted: 03/27/2024] [Indexed: 04/09/2024]
Abstract
PURPOSE There is limited clinical data for recommendations on how to deliver thoracic radiation therapy (TRT) concurrently with chemotherapy in limited-stage small cell lung cancer. We reviewed radiation therapy treatment plans in a randomized phase 2 trial comparing high-dose with standard-dose twice-daily TRT to assess treatment planning techniques, dose-volume data for target volumes and organs at risk (OARs), evaluate compliance with the protocol, associations with radiation-induced toxicity, and whether an imbalance in treatment planning parameters might be a reason for the large survival benefit of the higher dose (median overall survival 43.6 vs 22.6 months). METHODS AND MATERIALS In the study, 170 patients were to receive 4 courses of platinum/etoposide and were randomized to receive twice-daily TRT of 60 Gy/40 fractions (fx) or 45 Gy/30 fx. TRT treatment plans for those who received 1 or more fx of TRT (n = 166) were analyzed. RESULTS The most common treatment planning technique was 3-dimensional conformal radiation therapy (67%). The 75th percentile of the reported dose-volume parameters for the OARs were within the protocol-recommended limits for both groups. Mean doses to the esophagus of 25.5 Gy (IQR, 20.2-31.3; 60 Gy/40 fx) and 24.3 Gy (IQR, 20.3-27.5; 45 Gy/30 fx) were associated with 21% and 18% ≥ grade 3 acute esophagitis, respectively. In the 60 Gy/40 fx group, a mean dose to the lungs of 16.5 Gy (IQR, 15.8-16.9), V20 Gy of 29.5% (IQR, 28.8-30.4), and V5 Gy of 65.6% (IQR, 61.5-68.7) led to ≥ grade 3 pneumonitis in 4% of the patients. There was no ≥ grade 3 pneumonitis in the 45 Gy/30 fx group. The treatment planning techniques, the percentage change in volumes between original and redelineated OARs, planning target volumes, relative doses, and laterality were well balanced between the randomly assigned groups. CONCLUSIONS Considering the incidences of severe radiation-induced toxicities were within the range of other recent trials, the reported doses to the OARs appear to be safe. Treatment planning parameters were well balanced between the randomly assigned groups, supporting that the survival benefit of the twice-daily 60 Gy/40 fx TRT schedule was due to the higher dose.
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Affiliation(s)
- Nina Levin
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway; Department of Oncology, St. Olavs Hospital, Trondheim, Norway.
| | - Kristin T Killingberg
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway; Department of Oncology, St. Olavs Hospital, Trondheim, Norway
| | - Tarje O Halvorsen
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway; Department of Oncology, St. Olavs Hospital, Trondheim, Norway
| | - Signe Danielsen
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway; Department of Oncology, St. Olavs Hospital, Trondheim, Norway; Department of Physics, Norwegian University of Science and Technology, NTNU, Trondheim, Norway
| | - Bjørn Henning Grønberg
- Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, NTNU, Trondheim, Norway; Department of Oncology, St. Olavs Hospital, Trondheim, Norway
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Graabak G, Grønberg BH, Killingberg KT, Halvorsen TO. Effect of FDG PET-CT for Staging and Radiotherapy Planning - A Comparison of Cohorts From Two Randomized Trials of Thoracic Radiotherapy in Limited-Stage SCLC. JTO Clin Res Rep 2024; 5:100688. [PMID: 39286339 PMCID: PMC11404135 DOI: 10.1016/j.jtocrr.2024.100688] [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: 01/15/2024] [Revised: 04/30/2024] [Accepted: 05/08/2024] [Indexed: 09/19/2024] Open
Abstract
Introduction 18F-fluorodeoxyglucose positron emission tomography-computed tomography (PET-CT) is recommended for staging and defining target volume in limited-stage SCLC, though the impact on outcomes compared with CT staging and elective nodal irradiation (ENI) is not well documented. We analyzed patients receiving 45 Gy/30 fractions in two randomized trials of thoracic radiotherapy (TRT) in limited-stage SCLC (HAST and THORA trials) to evaluate whether PET-CT for staging and radiotherapy planning reduces radiotoxicity and improves survival. Methods Patients in HAST were staged with CT of the thorax and upper abdomen and brain magnetic resonance imaging of the brain. Patients in THORA were staged with PET-CT in addition. All patients were to receive four courses of platinum/etoposide chemotherapy and concurrent TRT starting three to four weeks after the first chemotherapy course. In HAST, target volumes included pathological lesions on CT plus ENI of lymph node stations 4-7 (bilateral). In THORA, target volumes were limited to PET-CT-positive lesions (selective nodal irradiation [SNI]). Results A total of 149 patients were included (PET-CT/SNI: n = 76, CT/ENI: n=73); the median age was 64 years, 56% were women, 85% had PS 0 to 1, and 81% had stage III disease. The PET-CT/SNI group experienced less grade 3-4 esophagitis (18% versus 33%, p = 0.043), less grade >=1 pneumonitis (5% versus 16%, p = 0.028), and less dysphagia after TRT (mean scores on European Organisation for Research and Treatment of Cancer 13-item lung cancer module: 45 versus 72). There was no difference in median overall survival (24 versus 25 mo, p = 0.59) or progression-free survival (11 versus 11 mo, p = 0.23). Conclusions Using PET-CT for staging and target volume definition of TRT reduces acute radiotoxicity but does not improve overall or progression-free survival in limited-stage SCLC.
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Affiliation(s)
- Gustav Graabak
- Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Oncology, St Olav's Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Bjørn Henning Grønberg
- Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Oncology, St Olav's Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Kristin Toftaker Killingberg
- Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Oncology, St Olav's Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Tarje Onsøien Halvorsen
- Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Oncology, St Olav's Hospital, Trondheim University Hospital, Trondheim, Norway
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Du K, Liao X, Kishi K. The Dose/Fractionation Debate in Limited-Stage Small Cell Lung Cancer. Cancers (Basel) 2024; 16:1908. [PMID: 38791986 PMCID: PMC11119808 DOI: 10.3390/cancers16101908] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Revised: 05/06/2024] [Accepted: 05/08/2024] [Indexed: 05/26/2024] Open
Abstract
To explore the most suitable dosage regimen for limited-stage small cell lung cancer (LS-SCLC) and provide references for clinical selection, strict inclusion criteria were applied, and studies were screened from Pubmed, Embase, and Web of Science. Subsequently, data on two-year overall survival rates and dosage regimens were collected, and scatter plots were constructed to provide a comprehensive perspective. The survival benefits of various dosage regimens were evaluated, and a linear quadratic equation was utilized to fit the relationship between the biologically effective dose (BED10) and the two-year overall survival rate. Among the five randomized controlled trials, the two-year overall survival rate of ConvTRT regimens with BED10 > 60 Gy (rough value) was only at or below the median of all ConvTRT regimens or all included study regimens, indicating that increasing the number and total dose of ConvTRT does not necessarily lead to better prognosis. In the exploration of HypoTRT regimens, there was a linear positive correlation between BED10 and the two-year overall survival rate (p < 0.0001), while the exploration of HyperTRT regimens was relatively limited, with the majority focused on the 45 Gy/30 F regimen. However, the current 45 Gy/30 F regimen is not sufficient to control LS-SCLC, resulting in a high local recurrence rate. High-dose ConvTRT regimens have long treatment durations and may induce tumor regrowth which may cause reduced efficacy. Under reasonable toxicity reactions, HyperTRT or HypoTRT with higher radiotherapy doses is recommended for treating LS-SCLC.
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Affiliation(s)
- Kaixin Du
- Department of Radiation Oncology, Xiamen Humanity Hospital, Fujian Medical University, Xiamen 361004, China;
| | - Xuehong Liao
- Department of Pathology, School of Medicine, Sapporo Medical University, Sapporo 060-8556, Japan;
| | - Kazushi Kishi
- Department of Radiation Oncology, National Disaster Medical Center, National Hospital Organization (NHO), Incorporated Administrative Agency, 3256 Midori-cho, Tachikawa-City 190-0014, Japan
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Kim WC, Won YK, Lee SM, Heo NH, Yeo SG, Chang AR, Bae SH, Kim JS, Yoo ID, Hong SP, Min CK, Jo IY, Kim ES. Evaluating the Necessity of Adaptive RT and the Role of Deformable Image Registration in Lung Cancer with Different Pathologic Classifications. Diagnostics (Basel) 2023; 13:2956. [PMID: 37761323 PMCID: PMC10527903 DOI: 10.3390/diagnostics13182956] [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: 07/31/2023] [Revised: 09/07/2023] [Accepted: 09/09/2023] [Indexed: 09/29/2023] Open
Abstract
BACKGROUND This study aimed to analyze differential radiotherapy (RT) responses according to the pathological type of lung cancer to see the possibility of applying adaptive radiotherapy (ART). METHODS ART planning with resampled-computed tomography was conducted for a total of 30 patients (20 non-small-cell lung cancer patients and 10 small-cell lung cancer patients) using a deformable image registration technique to reveal gross tumor volume (GTV) changes according to the duration of RT. RESULTS The small-cell lung cancer group demonstrated an average GTV reduction of 20.95% after the first week of initial treatment (p = 0.001), whereas the adenocarcinoma and squamous cell carcinoma groups showed an average volume reduction of 20.47% (p = 0.015) and 12.68% in the second week. The application of ART according to the timing of GTV reduction has been shown to affect changes in radiation dose irradiated to normal tissues. This suggests that ART applications may have to be different depending on pathological differences in lung cancer. CONCLUSION Through these results, the present study proposes the possibility of personalized treatment options for individual patients by individualizing ART based on specific radiation responses by pathologic types of lung cancer.
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Affiliation(s)
- Woo Chul Kim
- Department of Radiation Oncology, Division of Medical Physics, Soonchunhyang University Cheonan Hospital, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Republic of Korea; (W.C.K.); (C.K.M.)
- Department of Radiation Oncology, Soonchunhyang University Cheonan Hospital, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Republic of Korea;
| | - Yong Kyun Won
- Department of Radiation Oncology, Soonchunhyang University Cheonan Hospital, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Republic of Korea;
| | - Sang Mi Lee
- Department of Nuclear Medicine, Soonchunhyang University Cheonan Hospital, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Republic of Korea; (S.M.L.); (I.D.Y.); (S.-p.H.)
| | - Nam Hun Heo
- Clinical Trial Center, Soonchunhyang University Cheonan Hospital, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Republic of Korea;
| | - Seung-Gu Yeo
- Department of Radiation Oncology, Soonchunhyang University Bucheon Hospital, 170, Jomaru-ro, Bucheon 14584, Republic of Korea; (S.-G.Y.); (S.H.B.)
| | - Ah Ram Chang
- Department of Radiation Oncology, Soonchunhyang University Seoul Hospital, 59, Daesagwan-ro, Yongsan-gu, Seoul 04401, Republic of Korea; (A.R.C.); (J.S.K.)
| | - Sun Hyun Bae
- Department of Radiation Oncology, Soonchunhyang University Bucheon Hospital, 170, Jomaru-ro, Bucheon 14584, Republic of Korea; (S.-G.Y.); (S.H.B.)
| | - Jae Sik Kim
- Department of Radiation Oncology, Soonchunhyang University Seoul Hospital, 59, Daesagwan-ro, Yongsan-gu, Seoul 04401, Republic of Korea; (A.R.C.); (J.S.K.)
| | - Ik Dong Yoo
- Department of Nuclear Medicine, Soonchunhyang University Cheonan Hospital, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Republic of Korea; (S.M.L.); (I.D.Y.); (S.-p.H.)
| | - Sun-pyo Hong
- Department of Nuclear Medicine, Soonchunhyang University Cheonan Hospital, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Republic of Korea; (S.M.L.); (I.D.Y.); (S.-p.H.)
| | - Chul Kee Min
- Department of Radiation Oncology, Division of Medical Physics, Soonchunhyang University Cheonan Hospital, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Republic of Korea; (W.C.K.); (C.K.M.)
- Department of Radiation Oncology, Soonchunhyang University Cheonan Hospital, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Republic of Korea;
| | - In Young Jo
- Department of Radiation Oncology, Soonchunhyang University Cheonan Hospital, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Republic of Korea;
| | - Eun Seog Kim
- Department of Radiation Oncology, Soonchunhyang University Cheonan Hospital, 31, Suncheonhyang 6-gil, Dongnam-gu, Cheonan 31151, Republic of Korea;
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10
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Allen SG, Dragovic AF, Yin HM, Bryant AK, Paximadis PA, Matuszak MM, Schipper MJ, Dess RT, Hayman JA, Dominello MM, Kestin LL, Movsas B, Jolly S, Bergsma DP. Prospective Evaluation of Limited-Stage Small Cell Lung Cancer Radiotherapy Fractionation Regimen Usage and Acute Toxicity in a Large Statewide Quality Collaborative. Pract Radiat Oncol 2023; 13:444-453. [PMID: 37100388 DOI: 10.1016/j.prro.2023.04.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/20/2023] [Revised: 04/11/2023] [Accepted: 04/12/2023] [Indexed: 04/28/2023]
Abstract
PURPOSE National guidelines on limited-stage small cell lung cancer (LS-SCLC) treatment give preference to a hyperfractionated regimen of 45 Gy in 30 fractions delivered twice daily; however, use of this regimen is uncommon compared with once-daily regimens. The purpose of this study was to characterize the LS-SCLC fractionation regimens used throughout a statewide collaborative, analyze patient and treatment factors associated with these regimens, and describe real-world acute toxicity profiles of once- and twice-daily radiation therapy (RT) regimens. METHODS AND MATERIALS Demographic, clinical, and treatment data along with physician-assessed toxicity and patient-reported outcomes were prospectively collected by 29 institutions within the Michigan Radiation Oncology Quality Consortium between 2012 and 2021 for patients with LS-SCLC. We modeled the influence of RT fractionation and other patient-level variables clustered by treatment site on the odds of a treatment break specifically due to toxicity with multilevel logistic regression. National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0, incident grade 2 or worse toxicity was longitudinally compared between regimens. RESULTS There were 78 patients (15.6% overall) treated with twice-daily RT and 421 patients treated with once-daily RT. Patients receiving twice-daily RT were more likely to be married or living with someone (65% vs 51%; P = .019) and to have no major comorbidities (24% vs 10%; P = .017). Once-daily RT fractionation toxicity peaked during RT, and twice-daily toxicity peaked within 1 month after RT. After stratifying by treatment site and adjusting for patient-level variables, once-daily treated patients had 4.11 (95% confidence interval, 1.31-12.87) higher odds of treatment break specifically due to toxicity than twice-daily treated patients. CONCLUSIONS Hyperfractionation for LS-SCLC remains infrequently prescribed despite the lack of evidence demonstrating superior efficacy or lower toxicity of once-daily RT. With peak acute toxicity after RT and lower likelihood of a treatment break with twice-daily fractionation in real-word practice, providers may start using hyperfractionated RT more frequently.
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Affiliation(s)
- Steven G Allen
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | | | - Huiying Maggie Yin
- Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | - Alex K Bryant
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Peter A Paximadis
- Department of Radiation Oncology, Spectrum Health Lakeland, St. Joseph, Michigan
| | - Martha M Matuszak
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Matthew J Schipper
- Department of Biostatistics, University of Michigan, Ann Arbor, Michigan
| | - Robert T Dess
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - James A Hayman
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan
| | - Michael M Dominello
- Department of Radiation Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan
| | - Larry L Kestin
- Michigan Healthcare Professionals, 21st Century Oncology, Farmington Hills, Michigan
| | - Benjamin Movsas
- Department of Radiation Oncology, Henry Ford Cancer Institute, Detroit, Michigan
| | - Shruti Jolly
- Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan.
| | - Derek P Bergsma
- Department of Radiation Oncology, Mercy Health Saint Mary's, Grand Rapids, Michigan.
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11
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Yang E, Shin YS, Joo JH, Choi W, Kim SS, Choi EK, Lee J, Song SY. Outcome of dose-escalated intensity-modulated radiotherapy for limited disease small cell lung cancer. Radiat Oncol J 2023; 41:199-208. [PMID: 37793629 PMCID: PMC10556837 DOI: 10.3857/roj.2023.00591] [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: 07/07/2023] [Revised: 09/08/2023] [Accepted: 09/11/2023] [Indexed: 10/06/2023] Open
Abstract
PURPOSE An optimal once-daily radiotherapy (RT) regimen is under investigation for definitive concurrent chemoradiotherapy (CCRT) in limited disease small cell lung cancer (LD-SCLC). We compared the efficacy and safety of dose escalation with intensity-modulated radiotherapy (IMRT). MATERIALS AND METHODS Between January 2016 and March 2021, patients treated with definitive CCRT for LD-SCLC with IMRT were retrospectively reviewed. Patients who received a total dose <50 Gy or those with a history of thoracic RT or surgery were excluded. The patients were divided into two groups (standard and dose-escalated) based on the total biologically effective dose (BED, α/β = 10) of 70 Gy. The chemotherapeutic regimen comprised four cycles of etoposide and cisplatin. RESULTS One hundred and twenty-two patients were analyzed and the median follow-up was 27.8 months (range, 4.4 to 76.9 months). The median age of the patients was 63 years (range, 35 to 78 years) and the majority had a history of smoking (86.0%). The 1- and 3-year overall survival rates of the escalated dose group were significantly higher than those of the standard group (93.5% and 50.5% vs. 76.7% and 33.3%, respectively; p = 0.008), as were the 1- and 3-year freedom from in-field failure rates (91.4% and 66.5% vs. 73.8% and 46.9%, respectively; p = 0.018). The incidence of grade 2 or higher acute and late pneumonitis was not significantly different between the two groups (p = 0.062, 0.185). CONCLUSION Dose-escalated once-daily CCRT with IMRT led to improved locoregional control and survival, with no increase in toxicity.
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Affiliation(s)
- Eunyeong Yang
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Young Seob Shin
- Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Ji Hyeon Joo
- Department of Radiation Oncology, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, Korea
| | - Wonsik Choi
- Department of Radiation Oncology, Gangneung Asan Hospital, University of Ulsan College of Medicine, Gangneung, 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
| | - Jaeha Lee
- 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
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12
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Yang B, Zhang W, Qiu J, Yu Y, Li J, Zheng B. The development and validation of a nomogram for predicting brain metastases after chemotherapy and radiotherapy in male small cell lung cancer patients with stage III. Aging (Albany NY) 2023; 15:6487-6502. [PMID: 37433033 PMCID: PMC10373973 DOI: 10.18632/aging.204865] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Accepted: 06/16/2023] [Indexed: 07/13/2023]
Abstract
OBJECTIVE The purpose of this research was to develop a model for brain metastasis (BM) in limited-stage small cell lung cancer (LS-SCLC) patients and to help in the early identification of high-risk patients and the selection of individualized therapies. METHODS Univariate and multivariate logic regression was applied to identify the independent risk factors of BM. A receiver operating curve (ROC) and nomogram for predicting the incidence of BM were then conducted based on the independent risk factors. The decision curve analysis (DCA) was performed to assess the clinical benefit of prediction model. RESULTS Univariate regression analysis showed that the CCRT, RT dose, PNI, LLR, and dNLR were the significant factors for the incidence of BM. Multivariate analysis showed that CCRT, RT dose, and PNI were independent risk factors of BM and were included in the nomogram model. The ROC curves revealed the area under the ROC (AUC) of the model was 0.764 (95% CI, 0.658-0.869), which was much higher than individual variable alone. The calibration curve revealed favorable consistency between the observed probability and predicted probability for BM in LS-SCLC patients. Finally, the DCA demonstrated that the nomogram provides a satisfactory positive net benefit across the majority of threshold probabilities. CONCLUSIONS In general, we established and verified a nomogram model that combines clinical variables and nutritional index characteristics to predict the incidence of BM in male SCLC patients with stage III. Since the model has high reliability and clinical applicability, it can provide clinicians with theoretical guidance and treatment strategy making.
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Affiliation(s)
- Baihua Yang
- Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China
| | - Wei Zhang
- Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China
| | - Jianjian Qiu
- Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China
| | - Yilin Yu
- Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China
| | - Jiancheng Li
- Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China
| | - Buhong Zheng
- Department of Radiation Oncology, Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China
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13
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Hyuck Kim B, Song C, Jae Kim H. No survival benefit with early incorporation of thoracic radiotherapy using daily fractionation in patients with limited-stage small cell lung cancer undergoing chemoradiotherapy in the modern era: A systematic review and meta-analysis. Radiother Oncol 2023; 184:109696. [PMID: 37150449 DOI: 10.1016/j.radonc.2023.109696] [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: 02/27/2023] [Revised: 04/23/2023] [Accepted: 05/01/2023] [Indexed: 05/09/2023]
Abstract
BACKGROUND When concurrent chemoradiotherapy (CCRT) is administered for limited-stage small cell lung cancer (LS-SCLC), the early incorporation of thoracic radiotherapy (TRT) is generally recommended. However, it is controversial if this approach is really beneficial with most commonly used daily fractionated TRT in the modern era. METHODS A systematic literature search was performed using several databases following the PRISMA guidelines from Jan 2000 to Nov 2022. We excluded twice-daily TRT-based studies. The hazard ratio (HR) for survival following late TRT as a primary effect size was pooled from comparisons within individual studies according to the timing of daily fractionated TRT (early vs. late). RESULTS A total of 10 studies including 10,164 analyzable patients met all inclusion criteria. 'Early' timing usually referred to TRT within 1-2 cycles of concurrent chemotherapy. The pooled results demonstrated that the risk of death was not significantly increased following late TRT compared with early TRT (HR 1.01, 95% CI 0.84-1.20, p = 0.94). All sensitivity analysis and planned subgroup analyses showed similar results. In comparison with early TRT, late TRT did not significantly increase the risk of progression (HR 0.94, 95% CI 0.80-1.11, p = 0.48). Furthermore, late TRT was beneficial in alleviating grade 3 or higher esophagitis (OR 0.42, p = 0.01), but no significant differences was found in pneumonitis (OR 0.62, p = 0.38), and neutropenia (OR 0.57, p = 0.11). No evidence of publication bias was found. CONCLUSIONS This is the first meta-analysis to support the late incorporation of TRT in managing patients with LS-SCLC undergoing daily fractionated CCRT in the modern era. This approach may not compromise survival and can prevent severe acute toxicities. Further prospective studies of the daily fractionated TRT timing are warranted.
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Affiliation(s)
- Byoung Hyuck Kim
- Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea; Departments of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Changhoon Song
- Department of Radiation Oncology, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hak Jae Kim
- Departments of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea.
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14
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Bogart J, Wang X, Masters G, Gao J, Komaki R, Gaspar LE, Heymach J, Bonner J, Kuzma C, Waqar S, Petty W, Stinchcombe TE, Bradley JD, Vokes E. High-Dose Once-Daily Thoracic Radiotherapy in Limited-Stage Small-Cell Lung Cancer: CALGB 30610 (Alliance)/RTOG 0538. J Clin Oncol 2023; 41:2394-2402. [PMID: 36623230 PMCID: PMC10150922 DOI: 10.1200/jco.22.01359] [Citation(s) in RCA: 43] [Impact Index Per Article: 21.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2022] [Revised: 08/16/2022] [Accepted: 11/22/2022] [Indexed: 01/11/2023] Open
Abstract
PURPOSE Although level 1 evidence supports 45-Gy twice-daily radiotherapy as standard for limited-stage small-cell lung cancer, most patients receive higher-dose once-daily regimens in clinical practice. Whether increasing radiotherapy dose improves outcomes remains to be prospectively demonstrated. METHODS This phase III trial, CALGB 30610/RTOG 0538 (ClinicalTrials.gov identifier: NCT00632853), was conducted in two stages. In the first stage, patients with limited-stage disease were randomly assigned to receive 45-Gy twice-daily, 70-Gy once-daily, or 61.2-Gy concomitant-boost radiotherapy, starting with either the first or second (of four total) chemotherapy cycles. In the second stage, allocation to the 61.2-Gy arm was discontinued following planned interim toxicity analysis, and the study continued with two remaining arms. The primary end point was overall survival (OS) in the intention-to-treat population. RESULTS Trial accrual opened on March 15, 2008, and closed on December 1, 2019. All patients randomly assigned to 45-Gy twice-daily (n = 313) or 70-Gy once-daily radiotherapy (n = 325) are included in this analysis. After a median follow-up of 4.7 years, OS was not improved on the once-daily arm (hazard ratio for death, 0.94; 95% CI, 0.76 to 1.17; P = .594). Median survival is 28.5 months for twice-daily treatment, and 30.1 months for once-daily treatment, with 5-year OS of 29% and 32%, respectively. Treatment was tolerable, and the frequency of severe adverse events, including esophageal and pulmonary toxicity, was similar on both arms. CONCLUSION Although 45-Gy twice-daily radiotherapy remains the standard of care, this study provides the most robust information available to help guide the choice of thoracic radiotherapy regimen for patients with limited-stage small-cell lung cancer.
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Affiliation(s)
- Jeffrey Bogart
- State University of New York Upstate Medical University, New York, NY
| | - Xiaofei Wang
- Alliance Statistics and Data Management Center, Duke University, Durham, NC
| | - Gregory Masters
- Delaware/Christiana Care NCORP, Helen Graham Cancer Center, Newark, DE
| | - Junheng Gao
- Alliance Statistics and Data Management Center, Duke University, Durham, NC
| | - Ritsuko Komaki
- MD Anderson Cancer Center, University of Texas, Houston, TX
| | - Laurie E. Gaspar
- University of Colorado Denver Health Science Center, Denver, CO
- University of Colorado School of Medicine, Aurora, CO
| | - John Heymach
- MD Anderson Cancer Center, University of Texas, Houston, TX
| | | | - Charles Kuzma
- Southeast Clinical Oncology Research Consortium NCORP, FirstHealth of the Carolinas-Moore Regional Hospital, Pinehurst, NC
| | - Saiama Waqar
- Washington University—Siteman Cancer Center, St Louis, MO
| | - William Petty
- Wake Forest University Health Sciences, Winston-Salem, NC
| | | | | | - Everett Vokes
- University of Chicago Comprehensive Cancer Center, Chicago, IL
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15
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Deek MP, Haigentz M, Jabbour SK. Waiting for Big Changes in Limited-Stage Small-Cell Lung Cancer: For Now, More of the Same. J Clin Oncol 2023; 41:2326-2330. [PMID: 36821803 DOI: 10.1200/jco.22.02316] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 11/16/2022] [Accepted: 01/19/2023] [Indexed: 02/25/2023] Open
Abstract
The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.Concurrent chemoradiotherapy remains central to the treatment of limited-stage small-cell lung cancer (SCLC). SCLC is one of the few tumors treated with twice-daily radiotherapy (RT) in the primary definitive setting, a regimen that was established when Intergroup 0096 demonstrated its superiority over once-daily RT. However, questions remained about the optimal chemoradiotherapy regimen given the low RT dose used in the once-daily RT arm of Intergroup 0096. CALGB 30610/RTOG 0538 and CONVERT attempted to establish whether dose-escalated once-daily RT was superior to twice-daily RT in limited-stage SCLC. Although both studies showed similar survival between treatment regimens, once-daily RT was not found to be superior to twice-daily RT, and trial design limited the ability to conclude dose-escalated once-daily RT as noninferior to twice-daily RT. Thus, twice-daily RT with concurrent chemotherapy remains a standard of care in limited-stage SCLC.
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Affiliation(s)
- Matthew P Deek
- Rutgers Cancer Institute, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ
| | - Missak Haigentz
- Rutgers Cancer Institute, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ
| | - Salma K Jabbour
- Rutgers Cancer Institute, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ
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16
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Thoracic Radiation in Limited Stage Small Cell Lung Cancer: Trends in Radiation Fractionation. Clin Lung Cancer 2023; 24:322-328. [PMID: 36828750 DOI: 10.1016/j.cllc.2023.02.001] [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: 11/07/2022] [Revised: 01/18/2023] [Accepted: 02/01/2023] [Indexed: 02/10/2023]
Abstract
INTRODUCTION Thoracic radiotherapy (TRT) is standard of care for limited-stage small cell lung cancer (LS-SCLC). Although initial data supported the use of twice-daily (BID) radiation to a dose of 45 Gy, recent trials have suggested similar efficacy with daily fractionation (QD) to a dose of 60 to 70 Gy. This study evaluates trends in treatment regimen in patients treated with TRT for LS-SCLC. MATERIALS AND METHODS The National Cancer Database (NCDB) was queried for patients with LS-SCLC treated with TRT between 2004 to 2017 grouped by RT fractionation QD vs. BID. Exclusion criteria were unknown stage, and unknown RT dose. Multivariable (MVA) analyses using logistic regression were performed to investigate factors associated with receipt of a specific fractionation schedule. RESULTS A total of 17,453 patients met inclusion criteria, with 4,996 receiving BID treatment and 12,457 receiving QD treatment. The most common QD dose was 60 Gy (48.9%). Overall, QD fractionation has increased (1.3%/year). In 2004, 45 Gy BID treatment (41.4%) was the dominant fractionation. By 2017, 60 Gy QD (45.2%) increased (1.9%/y) to be the dominant fractionation, while 45 Gy BID (24.8%) decreased (-1.4%/y) to be the second most common fractionation. On MVA, factors that affect 1 treatment over the other were further stratified. CONCLUSION Since 2004, QD fractionation has been the preferred TRT regimen for patients with LS-SCLC compared to BID fractionation, with the proportion of patients getting QD treatment continuing to increase. The choice of treatment regimen appears to be influenced by both patient and facility characteristics.
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17
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Kim BH, Chung JH, Son J, Kim S, Wu HG, Kim HJ. Analysis of Once-Daily Thoracic Radiotherapy Dose According to the Underlying Lung Disease in Patients with Limited-Stage Small Cell Lung Cancer Undergoing Concurrent Chemoradiotherapy. Cancer Res Treat 2023; 55:73-82. [PMID: 35287254 PMCID: PMC9873322 DOI: 10.4143/crt.2021.1202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Accepted: 03/09/2022] [Indexed: 02/04/2023] Open
Abstract
PURPOSE In the treatment of concurrent chemoradiotherapy (CCRT) in limited-stage small cell lung cancer, the optimal once-daily radiotherapy (RT) dose/fractionation remain unclear although it is the most frequently used. Therefore, this study aimed to compare the treatment outcomes and toxicities of modest dose RT (≤ 54 Gy) with those of standard dose RT (> 54 Gy) and investigate the benefit of the high dose based on patient factors. MATERIALS AND METHODS Since 2004, our institution has gradually increased the thoracic RT dose. Among the 225 patients who underwent CCRT, 84 patients (37.3%) received > 54 Gy. Because the patients treated with RT > 54 Gy were not randomly assigned, propensity score matching (PSM) was performed. RESULTS The proportion of patients treated with > 54 Gy increased over time (p=0.014). Multivariate analysis revealed that the overall tumor stage and dose > 54 Gy (hazard ratio, 0.65; p=0.029) were independent prognostic factors for overall survival (OS). PSM confirmed that thoracic RT doses of > 54 Gy showed significantly improved progression-free survival (3-year, 42.7% vs. 24.0%; p < 0.001) and OS (3-year, 56.2% vs. 38.5%; p=0.003). Sensitivity analysis also showed that 60 Gy resulted in better survival than 54 Gy. However, in patients with underlying lung disease, OS benefit from > 54 Gy was not observed but considerable rates of severe pulmonary toxicities were observed (p=0.001). CONCLUSION Our analysis supports that the 60 Gy RT dose should be considered in the once-daily regimen of CCRT for limited-stage small cell lung cancer without underlying lung disease, but RT dose > 54 Gy did not seem to benefit for patients with chronic obstructive pulmonary disease or interstitial lung disease. Further study is needed to validate these results.
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Affiliation(s)
- Byoung Hyuck Kim
- Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul,
Korea,Department of Radiation Oncology, Seoul National University College of Medicine, Seoul,
Korea
| | - Joo-Hyun Chung
- Department of Radiation Oncology, Seoul National University Hospital, Seoul,
Korea
| | - Jaeman Son
- Department of Radiation Oncology, Seoul National University Hospital, Seoul,
Korea
| | - Suzy Kim
- Department of Radiation Oncology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul,
Korea
| | - Hong-Gyun Wu
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul,
Korea,Department of Radiation Oncology, Seoul National University Hospital, Seoul,
Korea,Department of Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul,
Korea,Cancer Research Institute, Seoul National University College of Medicine, Seoul,
Korea
| | - Hak Jae Kim
- Department of Radiation Oncology, Seoul National University College of Medicine, Seoul,
Korea,Department of Radiation Oncology, Seoul National University Hospital, Seoul,
Korea,Department of Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul,
Korea,Cancer Research Institute, Seoul National University College of Medicine, Seoul,
Korea
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18
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Qiu J, Ke D, Lin H, Yu Y, Zheng Q, Li H, Zheng H, Liu L, Li J. Using inflammatory indexes and clinical parameters to predict radiation esophagitis in patients with small-cell lung cancer undergoing chemoradiotherapy. Front Oncol 2022; 12:898653. [PMID: 36483030 PMCID: PMC9722947 DOI: 10.3389/fonc.2022.898653] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Accepted: 11/07/2022] [Indexed: 11/15/2023] Open
Abstract
OBJECTIVE Radiation esophagitis (RE) is a common adverse effect in small cell lung cancer (SCLC) patients undergoing thoracic radiotherapy. We aim to develop a novel nomogram to predict the acute severe RE (grade≥2) receiving chemoradiation in SCLC patients. MATERIALS AND METHODS the risk factors were analyzed by logistic regression, and a nomogram was constructed based on multivariate analysis results. The clinical value of the model was evaluated using the area under the receiver operating curve (ROC) curve (AUC), calibration curves, and decision curve analysis (DCA). The correlations of inflammation indexes were assessed using Spearman correlation analysis. RESULTS Eighty-four of 187 patients (44.9%) developed grade ≥2 RE. Univariate analysis indicated that concurrent chemoradiotherapy (CCRT, p < 0.001), chemotherapy cycle (p = 0.097), system inflammation response index (SIRI, p = 0.048), prognostic-nutrition index (PNI, p = 0.073), platelets-lymphocyte radio (PLR, p = 0.026), platelets-albumin ratio (PAR, p = 0.029) were potential predictors of RE. In multivariate analysis, CCRT [p < 0.001; OR, 3.380; 95% CI, 1.767-6.465], SIRI (p = 0.047; OR, 0.436; 95% CI, 0.192-0.989), and PAR (p = 0.036; OR, 2.907; 95% CI, 1.071-7.891) were independent predictors of grade ≥2 RE. The AUC of nomogram was 0.702 (95% CI, 0.626-0.778), which was greater than each independent predictor (CCRT: 0.645; SIRI: 0.558; PAR: 0.559). Calibration curves showed high coherence between the predicted and actual observation RE, and DCA displayed satisfactory clinical utility. CONCLUSION In this study, CCRT, SIRI, and PAR were independent predictors for RE (grade ≥2) in patients with SCLC receiving chemoradiotherapy. We developed and validated a predictive model through these factors. The developed nomogram with superior prediction ability can be used as a quantitative model to predict RE.
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Affiliation(s)
| | | | | | | | | | | | | | | | - Jiancheng Li
- Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou, China
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19
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Merie R, Gee H, Hau E, Vinod S. An Overview of the Role of Radiotherapy in the Treatment of Small Cell Lung Cancer - A Mainstay of Treatment or a Modality in Decline? Clin Oncol (R Coll Radiol) 2022; 34:741-752. [PMID: 36064636 DOI: 10.1016/j.clon.2022.08.024] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2022] [Revised: 06/16/2022] [Accepted: 08/10/2022] [Indexed: 01/31/2023]
Abstract
AIMS Small cell lung cancer (SCLC) accounts for about 15% of all lung cancers. Chemotherapy, immunotherapy and radiotherapy all play important roles in the management of SCLC. The aim of this study was to provide a comprehensive overview of the role and evidence of radiotherapy in the cure and palliation of SCLC. MATERIALS AND METHODS The search strategy included a search of the PubMed database, hand searches, reference lists of relevant review articles and relevant published abstracts. CLINICALTRIALS gov was also queried for relevant trials. RESULTS Thoracic radiotherapy improves overall survival in limited stage SCLC, but the timing and dose remain controversial. The role of thoracic radiotherapy in extensive stage SCLC with immunotherapy is the subject of several ongoing trials. Current evidence supports the use of prophylactic cranial irradiation (PCI) for limited stage SCLC but the evidence is equivocal in extensive stage SCLC. Whole brain radiotherapy is well established for the treatment of brain metastases but evidence is rapidly accumulating for the use of stereotactic radiosurgery. Further studies will define the role of PCI, whole brain radiotherapy and hippocampal avoidant PCI in the immunotherapy era. CONCLUSION Radiotherapy is an essential component in the multimodality management of SCLC. Technological advances have allowed safer delivery of radiotherapy with reduced toxicities. Discussion at multidisciplinary team meetings is important to ensure radiotherapy is considered and offered in appropriate patients.
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Affiliation(s)
- R Merie
- Icon Cancer Centre, Concord Repatriation General Hospital, Concord, NSW, Australia; South West Sydney Clinical Campuses, University of NSW, Liverpool, NSW, Australia.
| | - H Gee
- Sydney West Radiation Oncology Network (SWRON), Sydney, NSW, Australia; Sydney Medical School, Westmead Hospital, University of Sydney, Sydney, NSW, Australia; Children's Medical Research Institute (CMRI), University of Sydney, Sydney, NSW, Australia
| | - E Hau
- Sydney West Radiation Oncology Network (SWRON), Sydney, NSW, Australia; Sydney Medical School, Westmead Hospital, University of Sydney, Sydney, NSW, Australia; The Westmead Institute for Medical Research (WIMR), Westmead, NSW, Australia
| | - S Vinod
- South West Sydney Clinical Campuses, University of NSW, Liverpool, NSW, Australia; Cancer Therapy Centre, Liverpool Hospital, Liverpool, NSW, Australia; Ingham Institute for Applied Medical Research, Liverpool, NSW, Australia
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Zhou W, Wang P, Ti X, Yin Y, Huang S, Yang Z, Li J, Chai G, Lyu B, Li Z, Zhou Y, Xiao F, Xu L, Shi M, Zhao L. Sequential Hypofractionated versus Concurrent Twice-Daily Radiotherapy for Limited-Stage Small-Cell Lung Cancer: A Propensity Score-Matched Analysis. Cancers (Basel) 2022; 14:cancers14163920. [PMID: 36010913 PMCID: PMC9406024 DOI: 10.3390/cancers14163920] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2022] [Revised: 08/09/2022] [Accepted: 08/10/2022] [Indexed: 11/16/2022] Open
Abstract
Background: As there are no randomized trials comparing twice-daily with sequential hypofractionated (sequential hypo) radiotherapy regimens for limited-stage small-cell lung cancer (LS-SCLC). This study aimed to compare these two regimens for LS-SCLC by propensity score-matched analysis (PSM). Methods: We retrospectively analyzed 108 LS-SCLC patients between January 2015 and July 2019. All patients received concurrent twice-daily or sequential hypo radiotherapy. The survival, failure patterns, and toxicities were evaluated before and after PSM. Results: Before PSM, multivariate analysis showed that patients treated with sequential hypo had a significantly better overall survival (OS) and distant metastasis-free survival (DMFS) (HR = 0.353, p = 0.009; HR = 0.483, p = 0.039, respectively). Total radiotherapy time ≥ 24 days and stage III (HR = 2.454, p = 0.004; HR = 2.310, p = 0.004, respectively) were poor prognostic indicators for OS. Patients with a total radiotherapy time ≥ 24 days and N2−3 were more likely to recur than others (HR = 1.774, p = 0.048; HR = 2.369, p = 0.047, respectively). N2−3 (HR = 3.032, p = 0.011) was a poor prognostic indicator for DMFS. After PSM, being aged ≥65 years was associated with poorer OS, relapse-free survival (RFS) and DMFS (p < 0.05). A total radiotherapy time of ≥24 days was a poor prognostic indicator for OS and RFS (HR = 2.671, p = 0.046; HR = 2.370, p = 0.054, respectively). Although there was no significant difference, the patients in the sequential hypo group had a trend towards a better OS. The failure pattern between the two groups showed no difference. More patients had grade 1−2 esophagitis in the twice-daily group (p = 0.001). Conclusions: After propensity matching, no difference was shown in survival and failure. The sequential hypo schedule was associated with comparable survival and less toxicity and may be used as an alternative to concurrent twice-daily regimens.
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Affiliation(s)
- Wei Zhou
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Pang Wang
- Out-Patient Department, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Xinyu Ti
- Department of Pulmonary Diseases and Critical Care Medicine, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Yutian Yin
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Shigao Huang
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Zhi Yang
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Jie Li
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Guangjin Chai
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Bo Lyu
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Zhaohui Li
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Yan Zhou
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Feng Xiao
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Lin Xu
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
| | - Mei Shi
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
- Correspondence: (M.S.); (L.Z.)
| | - Lina Zhao
- Department of Radiation Oncology, Xijing Hospital, Air Force Medical University, Xi’an 710032, China
- Correspondence: (M.S.); (L.Z.)
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Viani GA, Gouveia AG, Matsuura FK, Jacinto AA, Moraes FY. Once daily (OD) versus twice-daily (BID) chemoradiation for limited stage small cell lung cancer (LS-SCLC): A meta-analysis of randomized clinical trials. Radiother Oncol 2022; 173:41-48. [PMID: 35101470 DOI: 10.1016/j.radonc.2022.01.032] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2021] [Revised: 12/27/2021] [Accepted: 01/20/2022] [Indexed: 10/19/2022]
Abstract
OBJECTIVES Assess Once daily (OD) chemoradiation effectiveness for LS-SCLC compared with twice daily (BID) chemoradiation. METHODS AND MATERIALS Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline, eligible randomized clinical trials (RCT) comparing OD and BID were identified on electronic databases. A meta-analysis was performed to compare overall survival (OS), progression-free survival (PFS), and toxicity. A metaregression analysis was conducted to explore the influence of fractionation, biological effective dose (BED), the proportion of patients treated with prophylactic cranial irradiation (PCI), elective nodal irradiation (ENI), and the start of radiotherapy (week 1 or week 4). RESULTS Five RCTs with a total of 1941 patients (OD vs. BID) were included. The relative risk (RR) for OS and PFS was 0.97 (CI95% 0.8-1.1, p = 0.731) and 0.90 (CI95% 0.7-1.1, p = 0.20) at 3-years. In the metaregression analysis, hypofractionated radiotherapy schedules were associated with an improvement in overall survival (p = 0.03). The start of radiotherapy (W1 or W4), BED, and ENI had no significant effect on OS and PFS. The complete response rate partial response and overall response rate for BID vs OD were 40% vs. 33% (p = 0.97), 50% vs. 57% (p = 0.94), and 89% vs. 93% (p = 0.99). The rate of completed planned RT 96% vs. 94% (p = 0.66), and the % of ≥4 chemotherapy cycles received 74% vs. 74% (p = 0.99), did not differ between OD and BID. The local and distant failure rates were not significantly different between OD and BID 40% vs. 33% (p = 0.88) and 36% vs. 36% (p = 0.99). No difference in grade 2 or grade 3 pneumonitis and esophagitis was observed among the groups (p = NS). CONCLUSION For LS-SCLC, OD conventional chemoradiation results in similar outcomes to BID chemoradiation. In contrast, hypofractionated radiotherapy was associated with a better OS and PFS than BID. Additional randomized phase III trials exploring hypofractionation with systemic therapy are warranted to validate our findings.
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Affiliation(s)
- Gustavo A Viani
- Ribeirão Preto Medical School, Department of Medical Imagings, Hematology and Oncology of University of São Paulo (FMRP-USP), Brazil.
| | - Andre G Gouveia
- Radiation Oncology Department - Américas Centro de Oncologia Integrado, Rio de Janeiro, Brazil
| | - Fernando K Matsuura
- Department of Medical Imagings, Hematology and Oncology of University of São Paulo (FMRP-USP), Brazil
| | | | - Fabio Y Moraes
- Department of Oncology - Division of Radiation Oncology, Kingston General Hospital, Queen's University, Kingston, Canada
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22
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Durvalumab with chemoradiotherapy for limited-stage small-cell lung cancer. Eur J Cancer 2022; 169:42-53. [DOI: 10.1016/j.ejca.2022.03.034] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Revised: 02/18/2022] [Accepted: 03/24/2022] [Indexed: 01/16/2023]
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Xu C, Li M, Cai X, Yuan S, Cao J, Zhu S, Chen M, Bi N, Hu X, Li J, Zhou W, Wang P, Zhao L, Liu N. Practice Patterns of Treatment Strategy of Limited-Stage Small-Cell Lung Cancer: Survey of Chinese Oncologists. Front Oncol 2022; 12:872324. [PMID: 35651806 PMCID: PMC9149654 DOI: 10.3389/fonc.2022.872324] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2022] [Accepted: 03/29/2022] [Indexed: 11/23/2022] Open
Abstract
Background Thoracic radiotherapy (TRT) with concurrent chemotherapy is the standard treatment of limited-stage small-cell lung cancer (LS-SCLC). However, there is still a controversy surrounding the treatment strategy especially optimal dosing and fractionation schedule. Current practice patterns among Chinese oncologists are unknown. Materials and Methods We surveyed 212 Chinese oncologists using a questionnaire including 50 questions designed by experienced oncologists. Questions covered demographic data, treatment recommendations, and self-assessed knowledge of guidelines or key clinical trials for SCLC. The chi-square test and Fisher's exact test were utilized to describe the result of the study. Results The response rate was 97% (207/212). Of all the respondents, 69% preferred TRT QD, 29% preferred BID, and 2% chose HFRT. For those who prefer TRT QD, 72% preferred a total dose of 60 Gy, followed by 15% opting for 66 Gy, 12% for <60 Gy, and 1% for 70 Gy. Of those who prefer BID, 79% preferred a total dose of 45 Gy, with 4% choosing 30 Gy, 8% choosing 50 Gy, 7% choosing 54 Gy, and 2% choosing >54 Gy. Regarding PCI, 82% of participants believed that PCI should be performed when treatment is completed and 13% believed that PCI should begin immediately after concurrent chemoradiotherapy. As for other therapies, 26% of participants choose concurrent anti-angiogenic therapy during SCLC treatment, and 49% recommended small-molecule TKI as the main anti-angiogenic therapy. Conclusion Substantial variation exists in how Chinese oncologists approach TRT dosing and fractionation for LS-SCLC. Almost 70% of respondents reported administering TRT QD more often in daily work. The most common doses were 60 Gy QD and 45 Gy BID.
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Affiliation(s)
- Chang Xu
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Meng Li
- Department of Radiation Oncology, Konggang Branch of Tianjin Cancer Hospital, Tianjin, China
| | - Xuwei Cai
- Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Shuanghu Yuan
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, China
| | - Jianzhong Cao
- Department of Radiation Oncology, Shanxi Cancer Hospital and the Affiliated Cancer Hospital of Shanxi Medical University, Taiyuan, China
| | - Shuchai Zhu
- Department of Radiation Oncology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
| | - Ming Chen
- Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Nan Bi
- Radiology Department, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xiao Hu
- Department of Radiation Oncology, Institute of Cancer Research and Basic Medical Sciences and University Cancer Hospital, Chinese Academy of Sciences, Zhejiang Cancer Hospital, Zhejiang Provincial Key Laboratory of Radiation Oncology, Hangzhou, China
| | - Jiancheng Li
- Department of Radiation Oncology, Fujian Provincial Cancer Hospital, Clinical College of Fujian Medical University, Fuzhou, China
| | - Wei Zhou
- Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, China
| | - Ping Wang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Lujun Zhao
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
| | - Ningbo Liu
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin, China
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Patient-reported health-related quality of life from a randomized phase II trial comparing standard-dose with high-dose twice daily thoracic radiotherapy in limited stage small-cell lung cancer. Lung Cancer 2022; 166:49-57. [DOI: 10.1016/j.lungcan.2022.02.002] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/03/2022] [Accepted: 02/06/2022] [Indexed: 11/21/2022]
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Bogart JA, Waqar SN, Mix MD. Radiation and Systemic Therapy for Limited-Stage Small-Cell Lung Cancer. J Clin Oncol 2022; 40:661-670. [PMID: 34985935 PMCID: PMC10476774 DOI: 10.1200/jco.21.01639] [Citation(s) in RCA: 71] [Impact Index Per Article: 23.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 08/12/2021] [Accepted: 09/01/2021] [Indexed: 12/14/2022] Open
Abstract
Progress in the overall treatment of small-cell lung cancer (SCLC) has moved at a slower pace than non-small-cell lung cancer. In fact, the standard treatment regimen for limited stage SCLC has not appreciably shifted in more than 20 years, consisting of four to six cycles of cisplatin and etoposide chemotherapy concurrent with thoracic radiotherapy (TRT) followed by prophylactic cranial irradiation (PCI) for responsive disease. Nevertheless, long-term outcomes have improved with median survival approaching 25-30 months, and approximately one third of patients now survive 5 years. This is likely attributable in part to improvements in staging, including use of brain magnetic resonance imaging and fluorodeoxyglucose-positron emission tomography imaging, advances in radiation treatment planning, and supportive care. The CONVERT and CALGB 30610 phase III trials failed to demonstrate a survival advantage for high-dose, once-daily TRT compared with standard 45 Gy twice-daily TRT, although high-dose, once-daily TRT remains common in practice. A phase III comparison of high-dose 60 Gy twice-daily TRT versus 45 Gy twice-daily TRT aims to confirm the provocative outcomes reported with 60 Gy twice daily in the phase II setting. Efforts over time have shifted from intensifying PCI, to attempting to reduce treatment-related neurotoxicity, to more recently questioning whether careful magnetic resonance imaging surveillance may obviate the routine need for PCI. The addition of immunotherapy has resulted in mixed success in extensive-stage SCLC with modest benefit observed with programmed death-ligand 1 inhibitors, and several ongoing trials assess programmed death-ligand 1 inhibition concurrent or adjuvant to chemoradiotherapy in limited-stage SCLC. Major advances in future treatment will likely depend on a better understanding and exploiting of molecular characteristics of SCLC with increasing personalization of therapy.
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Affiliation(s)
- Jeffrey A. Bogart
- State University of New York Upstate Medical University, Syracuse, NY
| | | | - Michael D. Mix
- State University of New York Upstate Medical University, Syracuse, NY
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Limited-Stage Small-Cell Lung Cancer: Current Progress and the Next Frontier. RADIATION 2021. [DOI: 10.3390/radiation1040026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Limited-stage (LS) small-cell lung cancer (SCLC) is defined as disease confined to a tolerable radiation portal without extrathoracic metastases. Despite clinical research over two decades, the prognosis of LS-SCLC patients remains poor. The current standard of care for LS-SCLC patients is concurrent platinum-based chemotherapy with thoracic radiotherapy (RT). Widespread heterogeneity on the optimal radiation dose and fractionation regimen among physicians highlights the logistical challenges of administering BID regimens. Prophylactic cranial irradiation (PCI) is recommended to patients following a good initial response to chemoradiation due to improved overall survival from historical trials and the propensity for LS-SCLC to recur with brain metastases. However, PCI utilization is being debated due to the greater availability of magnetic resonance imaging (MRI) and data in extensive-stage SCLC regarding close MRI surveillance in lieu of PCI while spurring novel RT techniques, such as hippocampal-avoidance PCI. Additionally, novel treatment combinations incorporating targeted small molecule therapies and immunotherapies with or following radiation for LS-SCLC have seen recent interest and some concepts are being investigated in clinical trials. Here, we review the landscape of progress, limitations, and challenges for LS-SCLC including current standard of care, novel radiation techniques, and the integration of novel therapeutic strategies for LS-SCLC.
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Graabak G, Grønberg BH, Sandvei MS, Nilssen Y, Halvorsen TO. Thoracic Radiotherapy in Limited-Stage Small-Cell Lung Cancer – a Population-Based Study of Patterns of Care in Norway from 2000 until 2018. JTO Clin Res Rep 2021; 3:100270. [PMID: 35146461 PMCID: PMC8801751 DOI: 10.1016/j.jtocrr.2021.100270] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2021] [Accepted: 12/14/2021] [Indexed: 11/29/2022] Open
Abstract
Introduction Twice-daily (BID) thoracic radiotherapy (TRT) of 45 Gy per 30 fractions is recommended for limited-stage (LS) SCLC, but most patients are treated with once-daily (OD) schedules owing to toxicity concerns and logistic challenges. An alternative is hypofractionated OD TRT of 40 to 42 Gy per 15 fractions. A randomized trial by our group indicated that TRT of 45 Gy per 30 fractions is more effective than TRT of 42 Gy per 15 fractions, and because it was not more toxic, 45 BID replaced 42 OD as the recommended schedule in Norway. The aims of this study were to evaluate to what extent BID TRT has been implemented in Norway and whether this practice change has led to improved survival. Methods Data on all patients diagnosed with LS SCLC from 2000 until 2018 were collected from the Cancer Registry of Norway, containing nearly complete data on cancer diagnosis, radiotherapy, and survival. Results A total of 2222 patients were identified; median age was 69 years, 51.8% were women, and 87.1% had stage II to III disease. Overall, 64.6% received TRT. The use of BID TRT increased from 1.8% (2000–2004) to 83.2% (2015–2018). Median overall survival among patients receiving curative TRT improved significantly during the study period (2000–2004: 17.9 mo, 2015–2018: 25.0 mo, p = 0.0023), and patients receiving 45 BID had significantly longer median overall survival than patients receiving 42 OD (BID: 26.2 mo, OD: 19.6 mo, p = 0.0015). Conclusions BID TRT has replaced hypofractionated OD TRT as the standard treatment of LS SCLC in Norway which has led to a significant (p = 0.0023) and clinically relevant survival improvement.
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Affiliation(s)
- Gustav Graabak
- Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
| | - Bjørn Henning Grønberg
- Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Oncology, St Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Marie Søfteland Sandvei
- Department of Oncology, St Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway
- Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
| | - Yngvar Nilssen
- Department of Registration, Cancer Registry of Norway, Oslo, Norway
| | - Tarje Onsøien Halvorsen
- Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Oncology, St Olav’s Hospital, Trondheim University Hospital, Trondheim, Norway
- Corresponding author. Address for correspondence: Tarje Onsøien Halvorsen, MD, PhD, Department of Clinical and Molecular Medicine, NTNU, Norwegian University of Science and Technology, 7491 Trondheim, Norway.
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Gjyshi O, Lin SH, Pezzi TA, Ning MS, Ma J, Liu S, Rusthoven CG. Care Patterns for Stereotactic Radiosurgery in Small Cell Lung Cancer Brain Metastases. Clin Lung Cancer 2021; 23:185-190. [PMID: 34419375 DOI: 10.1016/j.cllc.2021.07.003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 06/24/2021] [Accepted: 07/05/2021] [Indexed: 11/03/2022]
Abstract
INTRODUCTION The historical standard of care for brain metastases (BMs) from small cell lung cancer (SCLC) has been whole-brain radiotherapy (WBRT). However, there is growing interest in upfront stereotactic radiosurgery (SRS) for select SCLC patients. MATERIALS AND METHODS We invited United State-based Radiation Oncologists (ROs) via email to answer an anonymous survey using a branching logic system addressing their use of SRS and WBRT for SCLC BMs. Wilcoxon rank-sum test and Fisher's exact test were used to compare differences in continuous and categorical variables, respectively. Multivariable logistic regression analyses were fitted for outcome variables including covariates with P < .10 obtained on univariable analysis. RESULTS In total, 309 ROs completed the survey and 290 (95.7%) reported that they would consider SRS for SCLC BMs under certain clinical circumstances. Across patient characteristics, the number of BMs was the most heavily weighted factor (mean 4.3/5 in importance), followed by performance status, cognitive function, and response to prior therapy. Fewer BMs were correlated with increased SRS use (55.8% offered SRS "very frequently" [>75% of cases] or "often" [51%-75% of cases] for 1 BM vs. 1.1% for >10 BM, P < .001). In situations where WBRT was preferred, concern for rapid intracranial progression (45.3%) and lack of high-level data (36.9%) were the most important factors. The majority (60.6%) were aware of a large recent international retrospective analysis (the FIRE-SCLC study) reporting similar OS between upfront SRS and WBRT; awareness of this study was the only respondent variable predictive of SRS use for limited BMs (19.2% of those aware of the study preferring SRS for limited [≤4] BMs before vs. 61% preferring SRS after the publication, P < .001). The majority of respondents (88.2%) expressed a willingness to enroll patients on a recently opened recently opened randomized trial, NRG-CC009, comparing SRS versus hippocampal-avoidance WBRT. CONCLUSIONS In the first survey of SRS for SCLC BMs, we observed a high level of physician openness to upfront SRS in SCLC, particularly for patients with limited numbers of BMs, as well as significant interest in generating prospective randomized data to clarify the role of SRS in this population.
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Affiliation(s)
- Olsi Gjyshi
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Steven H Lin
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Todd A Pezzi
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Matthew S Ning
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Junsheng Ma
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Suyu Liu
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Chad G Rusthoven
- Department of Radiation Oncology, Colorado University School of Medicine, Aurora, CO.
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A Comparison of Hypofractionated and Twice-Daily Thoracic Irradiation in Limited-Stage Small-Cell Lung Cancer: An Overlap-Weighted Analysis. Cancers (Basel) 2021; 13:cancers13122895. [PMID: 34207857 PMCID: PMC8229231 DOI: 10.3390/cancers13122895] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2021] [Revised: 06/03/2021] [Accepted: 06/04/2021] [Indexed: 11/16/2022] Open
Abstract
Despite evidence for the superiority of twice-daily (BID) radiotherapy schedules, their utilization in practice remains logistically challenging. Hypofractionation (HFRT) is a commonly implemented alternative. We aim to compare the outcomes and toxicities in limited-stage small-cell lung cancer (LS-SCLC) patients treated with hypofractionated versus BID schedules. A bi-institutional retrospective cohort review was conducted of LS-SCLC patients treated with BID (45 Gy/30 fractions) or HFRT (40 Gy/15 fractions) schedules from 2007 to 2019. Overlap weighting using propensity scores was performed to balance observed covariates between the two radiotherapy schedule groups. Effect estimates of radiotherapy schedule on overall survival (OS), locoregional recurrence (LRR) risk, thoracic response, any ≥grade 3 (including lung, and esophageal) toxicity were determined using multivariable regression modelling. A total of 173 patients were included in the overlap-weighted analysis, with 110 patients having received BID treatment, and 63 treated by HFRT. The median follow-up was 20.4 months. Multivariable regression modelling did not reveal any significant differences in OS (hazard ratio [HR] 1.67, p = 0.38), LRR risk (HR 1.48, p = 0.38), thoracic response (odds ratio [OR] 0.23, p = 0.21), any ≥grade 3+ toxicity (OR 1.67, p = 0.33), ≥grade 3 pneumonitis (OR 1.14, p = 0.84), or ≥grade 3 esophagitis (OR 1.41, p = 0.62). HFRT, in comparison to BID radiotherapy schedules, does not appear to result in significantly different survival, locoregional control, or toxicity outcomes.
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Bogart JA, Wang X, Masters GA, Gao J, Komaki R, Gaspar LE, Heymach JV, Dobelbower MC, Kuzma C, Stinchcombe TE, Vokes EE. Short Communication: Interim toxicity analysis for patients with limited stage small cell lung cancer (LSCLC) treated on CALGB 30610 (Alliance) / RTOG 0538. Lung Cancer 2021; 156:68-71. [PMID: 33894496 PMCID: PMC8418826 DOI: 10.1016/j.lungcan.2021.04.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 04/11/2021] [Accepted: 04/14/2021] [Indexed: 11/18/2022]
Abstract
INTRODUCTION The CALGB 30610/RTOG 0538 randomized trial was designed to test whether high-dose thoracic radiotherapy (TRT) would improve survival compared with 45 Gy twice-daily (BID) TRT in limited stage small cell lung cancer (LSCLC). Two piloted experimental TRT regimens were of interest to study, 70 Gy daily (QD) and 61.2 Gy concomitant boost (CB). Driven by concerns about adequate patient accrual, a study design was employed that eliminated one experimental TRT arm based on early interim toxicity and tolerability, with the study then continuing as a traditional 2-arm phase III study. METHODS Patients with LSCLC were assigned to receive four cycles of cisplatin and etoposide chemotherapy with one of 3 TRT regimens starting with either the first or second cycle of chemotherapy. The interim endpoint was the cumulative highest toxicity calculated from a scoring system based on treatment-related grade 3 and higher toxicity and the ability to complete therapy in the experimental arms. RESULTS The final interim analysis was performed after 70 patients accrued to each experimental cohort, and a difference in treatment related toxicity scoring was not found (p = 0.739). Severe esophageal toxicity was comparable in both cohorts. Pulmonary toxicity was low overall, though 4 patients (5.7 %) on the 61.2 Gy arm developed grade 4 dyspnea, which was not observed in the 70 Gy arm. A protocol mandated decision was made to discontinue the 61.2 Gy arm following review of toxicity with the Data and Safety Monitoring Board. CONCLUSION A randomized trial design using a planned early interim toxicity analysis to discriminate between experimental treatment arms is feasible in a phase III setting. Refinement of the design could increase the likelihood of detecting clinically meaningful differences in toxicity in future studies.
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Affiliation(s)
- Jeffrey A Bogart
- State University of New York Upstate Medical University, Syracuse, NY, United States.
| | - Xiaofei Wang
- Alliance Statistics and Data Center, Duke University, Durham, NC, United States
| | | | - Junheng Gao
- Alliance Statistics and Data Center, Duke University, Durham, NC, United States
| | | | - Laurie E Gaspar
- Banner MD Anderson Cancer Center, Greeley, CO, United States
| | - John V Heymach
- MD Anderson Cancer Center, University of Texas, Houston, TX, United States
| | | | - Charles Kuzma
- FirstHealth of the Carolinas-Moore Regional Hospital, Pinehurst, NC, United States
| | - Thomas E Stinchcombe
- Duke Cancer Institute, Duke University Medical Center, Durham, NC, United States
| | - Everett E Vokes
- University of Chicago Comprehensive Cancer Center, Chicago, IL, United States
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Levy A, Botticella A, Le Péchoux C, Faivre-Finn C. Thoracic radiotherapy in small cell lung cancer-a narrative review. Transl Lung Cancer Res 2021; 10:2059-2070. [PMID: 34012814 PMCID: PMC8107758 DOI: 10.21037/tlcr-20-305] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Small-cell lung cancer (SCLC) represents 10–15% of all lung cancers and has a poor prognosis. Thoracic radiotherapy plays a central role in current SCLC management. Concurrent chemoradiotherapy (CTRT) is the standard of care for localised disease (stage I−III, limited-stage, LS). Definitive thoracic radiotherapy may be offered in metastatic patients (stage IV, extensive stage, ES-SCLC) after chemotherapy. For LS-SCLC, the gold standard is early accelerated hyperfractionated twice-daily CTRT (4 cycles of cisplatin etoposide, starting with the first or second chemotherapy cycle). Modern radiation techniques should be used with involved-field radiotherapy based on baseline CT and PET/CT scans. In ES-SCLC, thoracic radiotherapy should be discussed in cases of initial bulky mediastinal disease/residual thoracic disease not progressing after induction chemotherapy. This strategy was however not assessed in recent trials establishing chemo-immunotherapy as the standard first line treatment in ES-SCLC. Future developments include technical radiotherapy advances and the incorporation of new drugs. Thoracic irradiation is delivered more precisely given technical developments (IMRT, image-guided radiotherapy, stereotactic radiotherapy), reducing the risks of severe adverse events. Stereotactic ablative radiotherapy may be discussed in rare early stage (T1 to 2, N0) inoperable patients. A number of current clinical trials are investigating immunoradiotherapy. In this review, we highlight the current role of thoracic radiotherapy and describe ongoing research in the integration of biological surrogate markers, advanced radiotherapy technologies and novel drugs in SCLC patients.
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Affiliation(s)
- Antonin Levy
- Department of Radiation Oncology, Institut d'Oncologie Thoracique (IOT), Gustave Roussy, Villejuif, France.,Univ Paris Sud, Université Paris-Saclay, Le Kremlin-Bicêtre, France.,INSERM U1030, Molecular Radiotherapy, Gustave Roussy, Université Paris-Saclay, Villejuif, France
| | - Angela Botticella
- Department of Radiation Oncology, Institut d'Oncologie Thoracique (IOT), Gustave Roussy, Villejuif, France
| | - Cécile Le Péchoux
- Department of Radiation Oncology, Institut d'Oncologie Thoracique (IOT), Gustave Roussy, Villejuif, France
| | - Corinne Faivre-Finn
- Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.,The Christie NHS Foundation Trust and Division of Cancer Sciences, University of Manchester, Manchester, UK
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Barros JM, Rizzo MM, Chiozza JO, Couñago F. Is there a place for optimizing thoracic radiotherapy in limited-stage small cell lung cancer after twenty years? World J Clin Oncol 2021; 12:1-5. [PMID: 33552934 PMCID: PMC7829628 DOI: 10.5306/wjco.v12.i1.1] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2020] [Revised: 11/15/2020] [Accepted: 11/28/2020] [Indexed: 02/06/2023] Open
Abstract
Thoracic radiotherapy (TRT) is one of the main treatments in limited-stage small cell lung cancer (LS-SCLC). Hyperfractionated TRT (45 Gy, 1.5 Gy twice daily) has been the standard of care (SOC) since Turrisi and colleagues published the results of their clinical trial in 1999. Two meta-analyses have demonstrated the benefits of concurrent chemotherapy and TRT in terms of intrathoracic disease control at 2 years and 3-year overall survival (OS). The phase 2 trial by Grønberg et al (2016) comparing once-daily hypofractionated TRT to twice-daily hyperfractionated TRT in LS-SCLC found similar outcomes in both groups in terms of response rate, progression-free survival (PFS), grade 3-4 adverse effects, and OS. The CONVERT trial, published in 2017, failed to demonstrate the superiority of the conventional scheme (once-daily TRT) vs twice-daily radiotherapy, despite the application of modern radiotherapy techniques and a quality assurance programme, thus confirming the twice-daily hyperfractionated regimen as the SOC. At the 2020 American Society of Clinical Oncology (ASCO) annual meeting, Grønberg et al reported preliminary findings from a phase 2 trial comparing two different TRT dose regimens (45 Gy vs 60 Gy), both administered twice daily. Those data demonstrated a marked improvement in 2-year survival rates in the high dose arm (70.2% vs 46.1%, P = 0.002), despite similar objective response rates and PFS outcomes. Those findings provide a new treatment alternative to consider: Hyperfractionated, high-dose TRT. However, the results of that trial will need to be validated in a large, randomized phase 3 study. The results of the phase 2 CALCG 30610 trial will help to clarify the optimal dose and regimen. The potential role of upfront immunotherapy, which early data suggest may improve OS, also needs to be determined.
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Affiliation(s)
- José Máximo Barros
- Department of Radiation Oncology, Radiotherapy Center, Hospital Universitario Austral, Vidt Oncologia Radiante, CABA 1425, Argentina
| | - Manglio Miguel Rizzo
- Department of Medical Oncology, Hospital Universitario Austral, Buenos Aires 1629, Argentina
| | - Jorge Oscar Chiozza
- Department of Radiation Oncology, Radiotherapy Center, Hospital Universitario Austral, Vidt Oncologia Radiante, CABA 1425, Argentina
| | - Felipe Couñago
- Department of Radiation Oncology, Hospital Universitario Quirónsalud Madrid, Hospital La Luz, Universidad Europea de Madrid, Madrid 28028, Spain
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Weddell J, Chiney MS, Bhatnagar S, Gibbs JP, Shebley M. Mechanistic Modeling of Intra-Tumor Spatial Distribution of Antibody-Drug Conjugates: Insights into Dosing Strategies in Oncology. Clin Transl Sci 2020; 14:395-404. [PMID: 33073529 PMCID: PMC7877868 DOI: 10.1111/cts.12892] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Accepted: 08/21/2020] [Indexed: 12/12/2022] Open
Abstract
Antibody drug conjugates (ADCs) provide targeted delivery of cytotoxic agents directly inside tumor cells. However, many ADCs targeting solid tumors have exhibited limited clinical efficacy, in part, due to insufficient penetration within tumors. To better understand the relationship between ADC tumor penetration and efficacy, previously applied Krogh cylinder models that explore tumor growth dynamics following ADC administration in preclinical species were expanded to a clinical framework by integrating clinical pharmacokinetics, tumor penetration, and tumor growth inhibition. The objective of this framework is to link ADC tumor penetration and distribution to clinical efficacy. The model was validated by comparing virtual patient population simulations to observed overall response rates from trastuzumab‐DM1 treated patients with metastatic breast cancer. To capture clinical outcomes, we expanded upon previous Krogh cylinder models to include the additional mechanism of heterogeneous tumor growth inhibition spatially across the tumor. This expansion mechanistically captures clinical response rates by describing heterogeneous ADC binding and tumor cell killing; high binding and tumor cell death close to capillaries vs. low binding, and high tumor cell proliferation far from capillaries. Sensitivity analyses suggest that clinical efficacy could be optimized through dose fractionation, and that clinical efficacy is primarily dependent on the ADC‐target affinity, payload potency, and tumor growth rate. This work offers a mechanistic basis to predict and optimize ADC clinical efficacy for solid tumors, allowing dosing strategy optimization to improve patient outcomes.
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Affiliation(s)
- Jared Weddell
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, Illinois, USA
| | - Manoj S Chiney
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, Illinois, USA
| | - Sumit Bhatnagar
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, Illinois, USA
| | - John P Gibbs
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, Illinois, USA
| | - Mohamad Shebley
- Clinical Pharmacology and Pharmacometrics, AbbVie Inc., North Chicago, Illinois, USA
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Noronha V, Sekhar A, Patil VM, Menon N, Joshi A, Kapoor A, Prabhash K. Systemic therapy for limited stage small cell lung carcinoma. J Thorac Dis 2020; 12:6275-6290. [PMID: 33209466 PMCID: PMC7656383 DOI: 10.21037/jtd-2019-sclc-11] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Systemic treatment in small cell lung carcinoma has been a challenge for oncologists for decades. The high propensity for recurrence is usually due to distant metastasis, which makes systemic treatment an essential component of treatment in small cell lung carcinoma. The regimen of cisplatin and etoposide (established in the mid-1980’s) concurrently with thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) remains the standard of care in limited stage disease. Despite numerous trials, this regimen has not been improved upon. The standard combination regimen of cisplatin and etoposide has been compared to alternative platinum-containing regimens with drugs like epirubicin, irinotecan, paclitaxel, topotecan, pemetrexed, amrubicin and belotecan. Non-platinum containing regimens like ifosfamide and etoposide have also been tested. Attempts to intensify therapy have included the addition of a third drug like paclitaxel, ifosfamide, tirapazamine, tamoxifen, and thalidomide. Maintenance therapy following induction with chemotherapy, vandetanib and interferon-alpha have also been attempted. Molecularly directed targeted therapies and immunotherapeutic agents are areas of active research. In this review, we discuss the various systemic therapy options in limited stage small cell lung carcinoma, from the historical regimens to the modern-day therapy and promising areas of research. We also discuss the role of growth factors, the optimal number of chemotherapy cycles, the use of prognostic and predictive factors, the optimal timing of chemotherapy and the treatment of special populations of patients including older patients, and patients with comorbidities.
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Affiliation(s)
- Vanita Noronha
- Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai; Homi Bhabha National Institute, Mumbai, India
| | - Anbarasan Sekhar
- Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai; Homi Bhabha National Institute, Mumbai, India
| | - Vijay Maruti Patil
- Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai; Homi Bhabha National Institute, Mumbai, India
| | - Nandini Menon
- Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai; Homi Bhabha National Institute, Mumbai, India
| | - Amit Joshi
- Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai; Homi Bhabha National Institute, Mumbai, India
| | - Akhil Kapoor
- Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai; Homi Bhabha National Institute, Mumbai, India
| | - Kumar Prabhash
- Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai; Homi Bhabha National Institute, Mumbai, India
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Zhao J, Zhang W, Er P, Chen X, Guan Y, Qian D, Wang J, Yuan Z, Zhao L, Wang P, Pang Q. Concurrent or Sequential Chemoradiotherapy after 3-4 Cycles Induction Chemotherapy for LS-SCLC with Bulky Tumor. J Cancer 2020; 11:4957-4964. [PMID: 32742443 PMCID: PMC7378916 DOI: 10.7150/jca.41136] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Accepted: 05/15/2020] [Indexed: 01/14/2023] Open
Abstract
The current study was to compare the efficacy and safety between concurrent and sequential chemoradiotherapy after 3-4 cycles of induction chemotherapy for limited-stage small-cell lung cancer (LS-SCLC) with bulky tumor. From July 2012 to September 2015, a total of 68 patients with stage IIIA and IIIB SCLC who had completed 3-4 cycles of etoposide plus cisplatin/carboplatin and achieved clinical complete response (cCR) or clinical partial response (cPR) were randomized into the two groups equally. The concurrent group received radiotherapy combined with oral etoposide and cisplatin and the sequential group received sequential chemoradiotherapy. Thoracic radiotherapy was performed using intensity-modulated radiation therapy (IMRT) with 95% PTV 60Gy/30 times. After completing chemoradiotherapy, patients received prophylactic cranial irradiation. The primary endpoint was progression-free survival (PFS), and secondary endpoints included overall survival (OS) and toxicity. The median follow-up time was 63.3 months (95% confidence interval [CI], 50.8-75.8). Better PFS and OS were observed in concurrent group (median PFS, 26.0 months [95% CI, 9.0-43.0] versus 13.1 months [95%CI, 9.7-16.6], p=0.023; median OS, 35.0 months [95% CI, 25.4-44.6] versus 22.0 months [95% CI, 17.0-27.1], p=0.015). There was no significant difference in the incidence of radiation esophagitis and radiation pneumonitis between the two groups (p=0.795, p=0.525). This study demonstrated that after the completion of 3-4 cycles of chemotherapy with a remission, concurrent chemoradiotherapy with oral etoposide and cisplatin improved survival compared with sequential chemoradiotherapy in LS-SCLC with bulky tumor. ClinicalTrials.gov Identifier: NCT01745445.
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Affiliation(s)
- Jingjing Zhao
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Wencheng Zhang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Puchun Er
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Xi Chen
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Yong Guan
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Dong Qian
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Jun Wang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Zhiyong Yuan
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Lujun Zhao
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Ping Wang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
| | - Qingsong Pang
- Department of Radiation Oncology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, China
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36
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Glatzer M, Faivre-Finn C, De Ruysscher D, Widder J, Van Houtte P, Troost EGC, Dahele MR, Slotman BJ, Ramella S, Pöttgen C, Peeters STH, Nestle U, McDonald F, Le Pechoux C, Dziadziuszko R, Belderbos J, Putora PM. Once daily versus twice-daily radiotherapy in the management of limited disease small cell lung cancer - Decision criteria in routine practise. Radiother Oncol 2020; 150:26-29. [PMID: 32447035 DOI: 10.1016/j.radonc.2020.05.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 04/24/2020] [Accepted: 05/03/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND In limited disease small cell lung cancer (LD-SCLC), the CONVERT trial has not demonstrated superiority of once-daily (QD) radiotherapy (66 Gy) over twice-daily (BID) radiotherapy (45 Gy). We explored the factors influencing the selection between QD and BID regimens. METHODS Thirteen experienced European thoracic radiation oncologists as selected by the European Society for Therapeutic Radiation Oncology (ESTRO) were asked to describe their strategies in the management of LD-SCLC. Treatment strategies were subsequently converted into decision trees and analysed for agreement and discrepancies. RESULTS Logistic reasons, patients' performance status and radiotherapy dose constraints were the three major decision criteria used by most experts in decision making. The use of QD and BID regimens was balanced among European experts, but there was a trend towards the BID regimen for fit patients able to travel twice a day to the radiotherapy site. CONCLUSION BID and QD radiotherapy are both accepted regimens among experts and the decision is influenced by pragmatic factors such as availability of transportation.
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Affiliation(s)
- Markus Glatzer
- Department of Radiation Oncology, Kantonsspital St. Gallen, Switzerland.
| | - Corinne Faivre-Finn
- Division of Cancer Sciences, University of Manchester & The Christie NHS Foundation Trust Manchester, United Kingdom
| | - Dirk De Ruysscher
- Maastricht University Medical Center, Department of Radiation Oncology (Maastro Clinic), School for Oncology and Developmental Biology (GROW), The Netherlands
| | - Joachim Widder
- Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Austria
| | - Paul Van Houtte
- Department Radiation Oncology, Institut Bordet, Université Libre Bruxelles, Belgium
| | - Esther G C Troost
- OncoRay - National Center for Radiation Research in Oncology, Germany; Department of Radiotherapy and Radiation Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus Dresden, Germany; Helmholtz-Zentrum Dresden - Rossendorf, Institute of Radiooncology - OncoRay, Germany; German Cancer Consortium (DKTK), Partner Site Dresden, Germany; and German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - M R Dahele
- Department of Radiation Oncology, Amsterdam University Medical Center, VUMC, The Netherlands
| | - Ben J Slotman
- Department of Radiation Oncology, Amsterdam University Medical Center, VUMC, The Netherlands
| | - Sara Ramella
- Department of RadiationOncology, Campus Bio-Medico University, Rome, Italy
| | - Christoph Pöttgen
- Department of Radiation Oncology, West German Tumor Centre, University of Duisburg-Essen Medical School, Germany
| | - Stephanie T H Peeters
- Maastricht University Medical Center, Department of Radiation Oncology (Maastro Clinic), School for Oncology and Developmental Biology (GROW), The Netherlands
| | - Ursula Nestle
- Department of Radiation Oncology, Kliniken Maria Hilf, Moenchengladbach, Germany; Department of Radiation Oncology, University Hospital Freiburg, Germany
| | - Fiona McDonald
- Department of Radiotherapy, The Royal Marsden NHS Foundation Trust, London, UK
| | | | | | - José Belderbos
- Department of Radiation Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands
| | - Paul M Putora
- Department of Radiation Oncology, Kantonsspital St. Gallen, Switzerland; Department of Radiation Oncology, University of Bern, Switzerland
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Levy A, Hendriks LEL, Le Péchoux C, Falk S, Besse B, Novello S, Dingemans AMC, Hasan B, Reck M, Berghmans T, Faivre-Finn C. Current management of limited-stage SCLC and CONVERT trial impact: Results of the EORTC Lung Cancer Group survey. Lung Cancer 2019; 136:145-147. [PMID: 31520867 DOI: 10.1016/j.lungcan.2019.08.007] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 08/07/2019] [Accepted: 08/08/2019] [Indexed: 12/28/2022]
Abstract
OBJECTIVES The CONVERT trial showed that twice-daily (BD) concurrent chemoradiotherapy should continue to be considered the standard of care in localised LS-SCLC. A survey was conducted to assess the impact of the CONVERT trial in clinical practice and to identify any relevant research questions for future trials in this setting. METHODS AND MATERIALS An EORTC Group online survey of LS-SCLC practice was distributed to the EORTC LCG and to members of several European thoracic oncology societies between April and December 2018. RESULTS 198 responses were analysed. The majority of respondents (88%, n = 174) were aware of the CONVERT trial. Radiation oncologists comprised 56% of all respondents. Once-daily (OD) radiotherapy is still the most commonly used regimen, however the use of concurrent BD radiotherapy increased after the publication of CONVERT (n = 59/186, 32% prior to and n = 78/187, 42% after the publication, p = 0.053). The main reasons for not implementing BD after the CONVERT publication were logistical issues (n = 88, 44%), inconvenience for patients (n = 56, 28%), and the absence of a statistical survival difference between the two arms in CONVERT (n = 38, 19%). Brain MRI was used by 28% during staging but more than half (60%) of the respondents did not routinely image the brain during follow-up. The main research questions of interest in LS-SCLC were 1) integrating novel targeted therapies-immunotherapies (n = 160, 81%), 2) PCI (+/- hippocampal sparing) vs. MRI surveillance (n = 140, 71%) and, 3) biomarker driven trials (n = 92, 46%). CONCLUSION Once daily radiotherapy (60-66 Gy in 30-33 fractions) remains the most prescribed radiotherapy fractionation, despite the findings suggested by the CONVERT trial.
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Affiliation(s)
- Antonin Levy
- Department of Radiation Oncology, Gustave Roussy, Institut d'Oncologie Thoracique (IOT), INSERM U1030 Molecular Radiotherapy, Université Paris-Saclay, F-94805, Villejuif, France; Univ Paris Sud, Université Paris-Saclay, F-94270, Le Kremlin-Bicêtre, France.
| | - Lizza E L Hendriks
- Department of Pulmonary Diseases, GROW - School for oncology and developmental biology, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Cécile Le Péchoux
- Department of Radiation Oncology, Gustave Roussy, Institut d'Oncologie Thoracique (IOT), INSERM U1030 Molecular Radiotherapy, Université Paris-Saclay, F-94805, Villejuif, France
| | - Sally Falk
- The University of Manchester, Division of Cancer Sciences, The Christie NHS Foundation Trust, Manchester, United Kingdom
| | - Benjamin Besse
- Univ Paris Sud, Université Paris-Saclay, F-94270, Le Kremlin-Bicêtre, France; Department of Medical Oncology, Gustave Roussy, Institut d'Oncologie Thoracique (IOT), Gustave Roussy, Université Paris-Saclay, F-94805, Villejuif, France
| | - Silvia Novello
- Oncology Department, University of Turin, AOU San Luigi, Orbassano (TO), Italy
| | - Anne-Marie C Dingemans
- Department of Pulmonary Diseases, GROW - School for oncology and developmental biology, Maastricht University Medical Center+, Maastricht, the Netherlands
| | - Baktiar Hasan
- European Organisation for Research and Treatment of Cancer, Brussels, Belgium
| | - Martin Reck
- LungenClinic Grosshansdorf, Airway Research Center North, German Center for Lung Research, Grosshansdorf, Germany
| | - Thierry Berghmans
- Department of Intensive Care and Oncological Emergencies & Thoracic Oncology, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium
| | - Corinne Faivre-Finn
- The University of Manchester, Division of Cancer Sciences, The Christie NHS Foundation Trust, Manchester, United Kingdom
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Shuryak I, Hall EJ, Brenner DJ. Optimized Hypofractionation Can Markedly Improve Tumor Control and Decrease Late Effects for Head and Neck Cancer. Int J Radiat Oncol Biol Phys 2019; 104:272-278. [DOI: 10.1016/j.ijrobp.2019.02.025] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Revised: 01/29/2019] [Accepted: 02/08/2019] [Indexed: 12/25/2022]
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