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

Bjørn Henning Grønberg; Kristin Toftaker Killingberg; Øystein Fløtten; Maria Moksnes Bjaanæs; Odd Terje Brustugun; Tesfaye Madebo; Seppo Wang Langer; Signe Lenora Risumlund; Tine Schytte; Nina Helbekkmo; Kirill Neumann; Øyvind Yksnøy; Jens Engleson; Sverre Fluge; Thor Naustdal; Liv Ellen Giske; Jan Nyman; Georgios Tsakonas; Tarje Onsøien Halvorsen

doi:10.1016/j.jtho.2025.04.007

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

Bjørn Henning Grønberg^*, Kristin Toftaker Killingberg, Øystein Fløtten, Maria Moksnes Bjaanæs, Odd Terje Brustugun, Tesfaye Madebo, Seppo Wang Langer, Signe Lenora Risumlund, Tine Schytte, Nina Helbekkmo, Kirill Neumann, Øyvind Yksnøy, Jens Engleson, Sverre Fluge, Thor Naustdal, Liv Ellen Giske, Jan Nyman, Georgios Tsakonas, Tarje Onsøien Halvorsen

^*Corresponding author af dette arbejde

Afdeling for Kræftbehandling CKO

4 Citationer (Scopus)

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 cm 3, 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.

Originalsprog	Engelsk
Tidsskrift	Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer
Vol/bind	20
Udgave nummer	8
Sider (fra-til)	1108-1119
Antal sider	12
ISSN	1556-0864
DOI	https://doi.org/10.1016/j.jtho.2025.04.007
Status	Udgivet - aug. 2025

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10.1016/j.jtho.2025.04.007Licens: CC BY

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Grønberg, B. H., Killingberg, K. T., Fløtten, Ø., Bjaanæs, M. M., Brustugun, O. T., Madebo, T., Langer, S. W., Risumlund, S. L., Schytte, T., Helbekkmo, N., Neumann, K., Yksnøy, Ø., Engleson, J., Fluge, S., Naustdal, T., Giske, L. E., Nyman, J., Tsakonas, G., & Halvorsen, T. O. (2025). 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. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 20(8), 1108-1119. https://doi.org/10.1016/j.jtho.2025.04.007

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. / Grønberg, Bjørn Henning; Killingberg, Kristin Toftaker; Fløtten, Øystein et al.
I: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, Bind 20, Nr. 8, 08.2025, s. 1108-1119.

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

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 2025, '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', Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, bind 20, nr. 8, s. 1108-1119. https://doi.org/10.1016/j.jtho.2025.04.007

Grønberg BH, Killingberg KT, Fløtten Ø, Bjaanæs MM, Brustugun OT, Madebo T et al. 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. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2025 aug.;20(8):1108-1119. Epub 2025 apr. 19. doi: 10.1016/j.jtho.2025.04.007

Grønberg, Bjørn Henning ; Killingberg, Kristin Toftaker ; Fløtten, Øystein et al. / 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. I: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer. 2025 ; Bind 20, Nr. 8. s. 1108-1119.

@article{9a6b038a94784687b7acb66e2201b592,

title = "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",

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 cm 3, 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.",

keywords = "Accelerated, Chemoradiotherapy, Dose escalation, LS SCLC, Radiotoxicity, Twice daily RT",

author = "Gr{\o}nberg, {Bj{\o}rn Henning} and Killingberg, {Kristin Toftaker} and {\O}ystein Fl{\o}tten and Bjaan{\ae}s, {Maria Moksnes} and Brustugun, {Odd Terje} and Tesfaye Madebo and Langer, {Seppo Wang} and Risumlund, {Signe Lenora} and Tine Schytte and Nina Helbekkmo and Kirill Neumann and {\O}yvind Yksn{\o}y and Jens Engleson and Sverre Fluge and Thor Naustdal and Giske, {Liv Ellen} and Jan Nyman and Georgios Tsakonas and Halvorsen, {Tarje Ons{\o}ien}",

year = "2025",

month = aug,

doi = "10.1016/j.jtho.2025.04.007",

language = "English",

volume = "20",

pages = "1108--1119",

journal = "Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer",

issn = "1556-0864",

publisher = "Elsevier Inc.",

number = "8",

}

TY - JOUR

T1 - High-Dose Versus Standard-Dose Twice-Daily Thoracic Radiotherapy in Limited-Stage SCLC

T2 - Final Survival Data, Long-Term Toxicity, and Relapse Patterns in a Randomized, Open-Label, Phase II Trial

AU - Grønberg, Bjørn Henning

AU - Killingberg, Kristin Toftaker

AU - Fløtten, Øystein

AU - Bjaanæs, Maria Moksnes

AU - Brustugun, Odd Terje

AU - Madebo, Tesfaye

AU - Langer, Seppo Wang

AU - Risumlund, Signe Lenora

AU - Schytte, Tine

AU - Helbekkmo, Nina

AU - Neumann, Kirill

AU - Yksnøy, Øyvind

AU - Engleson, Jens

AU - Fluge, Sverre

AU - Naustdal, Thor

AU - Giske, Liv Ellen

AU - Nyman, Jan

AU - Tsakonas, Georgios

AU - Halvorsen, Tarje Onsøien

PY - 2025/8

Y1 - 2025/8

N2 - 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 cm 3, 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.

AB - 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 cm 3, 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.

KW - Accelerated

KW - Chemoradiotherapy

KW - Dose escalation

KW - LS SCLC

KW - Radiotoxicity

KW - Twice daily RT

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U2 - 10.1016/j.jtho.2025.04.007

DO - 10.1016/j.jtho.2025.04.007

M3 - Journal article

C2 - 40258573

SN - 1556-0864

VL - 20

SP - 1108

EP - 1119

JO - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

JF - Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

IS - 8

ER -

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

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