Isotoxic Intensity Modulated Radiation Therapy in Stage III Non-Small Cell Lung Cancer: A Feasibility Study

Kate Haslett; Neil Bayman; Kevin Franks; Nicki Groom; Susan V. Harden; Catherine Harris; Gerard Hanna; Stephen Harrow; Matthew Hatton; Paula McCloskey; Fiona McDonald; W. David Ryder; Corinne Faivre-Finn

doi:10.1016/j.ijrobp.2020.11.040

Isotoxic Intensity Modulated Radiation Therapy in Stage III Non-Small Cell Lung Cancer: A Feasibility Study

Kate Haslett, Neil Bayman, Kevin Franks, Nicki Groom, Susan V. Harden, Catherine Harris, Gerard Hanna, Stephen Harrow, Matthew Hatton, Paula McCloskey, Fiona McDonald, W. David Ryder, Corinne Faivre-Finn^*

^*Corresponding author for this work

Patrick G Johnston Centre for Cancer Research

Research output: Contribution to journal › Article › peer-review

18 Citations (Scopus)

109 Downloads (Pure)

Abstract

Purpose: Not all patients with stage III non-small cell lung cancer (NSCLC) are suitable for concurrent chemoradiation therapy (CRT). Local failure rate is high for sequential concurrent CRT. As such, there is a rationale for treatment intensification.

Methods and Materials: Isotoxic intensity modulated radiation therapy (IMRT) is a multicenter feasibility study that combines different intensification strategies including hyperfractionation, acceleration, and dose escalation facilitated by IMRT. Patients with unresectable stage III NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and unsuitable for concurrent CRT were recruited. A minimum of 2 cycles of platinum-based chemotherapy was compulsory before starting radiation therapy (RT). Radiation dose was increased until a maximum dose of 79.2 Gy was reached or 1 or more of the organs at risk met predefined constraints. RT was delivered in 1.8-Gy fractions twice daily, and an RT quality assurance program was implemented. The primary objective was the delivery of isotoxic IMRT to a dose >60 Gy equivalent dose in 2-Gy fractions (EQD2 assuming an α/β ratio of 10 Gy for acute reacting tissues).

Results: Thirty-seven patients were recruited from 7 UK centers. Median age was 69.9 years (range, 46-86 years). The male-to-female ratio was 17:18. ECOG PS was 0 to 5 in 14.2% of patients; PS was 1 to 27 in 77.1% of patients; PS was 2 to 3 in 8.6% of patients. Stage IIIA:IIIB ratio was 22:13 (62.9%:37.1%). Of 37 patients, 2 (5.4%) failed to achieve EQD2 > 60 Gy. Median prescribed tumor dose was 77.4 Gy (range, 61.2-79.2 Gy). A maximum dose of 79.2Gy was achieved in 14 patients (37.8%). Grade 3 esophagitis was reported in 2 patients, and no patients developed grade 3 to 4 pneumonitis. There were 3 grade 5 events: acute radiation pneumonitis, bronchopulmonary hemorrhage, and acute lung infection. Median follow-up at time of analysis was 25.4 months (range, 8.0-44.2) months for 11 of 35 survivors. The median survival was 18.1 months (95% confidence interval [CI], 13.9-30.6), 2-year overall survival was 33.6% (95% CI, 17.9-50.1), and progression-free survival was 23.9% (95% CI, 11.3-39.1).

Conclusions: Isotoxic IMRT is a well-tolerated and feasible approach to treatment intensification.

Original language	English
Pages (from-to)	1341-1348
Number of pages	8
Journal	International Journal of Radiation Oncology Biology Physics
Volume	109
Issue number	5
Early online date	11 Mar 2021
DOIs	https://doi.org/10.1016/j.ijrobp.2020.11.040
Publication status	Published - 01 Apr 2021

Bibliographical note

Funding Information:
This research is jointly funded by Cancer Research UK's (CRUK) Clinical Trials Awards and Advisory Committee (CTAAC) & British Lung Foundation (grant reference number C17052/A15702). C.F-F. is supported by the NIHR Manchester Biomedical Research Center.

Funding Information:
The authors acknowledge the support of Damian Mullan and Ben Taylor (radiology input), Carl Rowbottom and Gareth Webster (protocol development), Dave Ardron (patient representative), Tsang Yatman/Elizabeth Miles/Romaana Mir (NCRI Radiation therapy Quality Assurance Group), Glenda Laviste (senior clinical trials nurse), Sally Falk (research project manager).

Funding Information:
This research is jointly funded by Cancer Research UK’s (CRUK) Clinical Trials Awards and Advisory Committee (CTAAC) & British Lung Foundation (grant reference number C17052/A15702). C.F-F. is supported by the NIHR Manchester Biomedical Research Center.

Publisher Copyright:
© 2020 The Authors

Keywords

Radiotherapy
Isotoxic
Lung cancer
Non-small cell lung cancer (NSCLC)
Dose Escalation
IMRT

ASJC Scopus subject areas

Radiation
Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Isotoxic Intensity Modulated Radiation Therapy in Stage III Non-Small Cell Lung Cancer: A Feasibility Study
Copyright 2022 the authors. This is an open access article published under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited.
Final published version, 294 KBLicence: CC BY-NC-ND

Cite this

Haslett, K., Bayman, N., Franks, K., Groom, N., Harden, S. V., Harris, C., Hanna, G., Harrow, S., Hatton, M., McCloskey, P., McDonald, F., Ryder, W. D., & Faivre-Finn, C. (2021). Isotoxic Intensity Modulated Radiation Therapy in Stage III Non-Small Cell Lung Cancer: A Feasibility Study. International Journal of Radiation Oncology Biology Physics, 109(5), 1341-1348. https://doi.org/10.1016/j.ijrobp.2020.11.040

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abstract = "Purpose: Not all patients with stage III non-small cell lung cancer (NSCLC) are suitable for concurrent chemoradiation therapy (CRT). Local failure rate is high for sequential concurrent CRT. As such, there is a rationale for treatment intensification. Methods and Materials: Isotoxic intensity modulated radiation therapy (IMRT) is a multicenter feasibility study that combines different intensification strategies including hyperfractionation, acceleration, and dose escalation facilitated by IMRT. Patients with unresectable stage III NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and unsuitable for concurrent CRT were recruited. A minimum of 2 cycles of platinum-based chemotherapy was compulsory before starting radiation therapy (RT). Radiation dose was increased until a maximum dose of 79.2 Gy was reached or 1 or more of the organs at risk met predefined constraints. RT was delivered in 1.8-Gy fractions twice daily, and an RT quality assurance program was implemented. The primary objective was the delivery of isotoxic IMRT to a dose >60 Gy equivalent dose in 2-Gy fractions (EQD2 assuming an α/β ratio of 10 Gy for acute reacting tissues). Results: Thirty-seven patients were recruited from 7 UK centers. Median age was 69.9 years (range, 46-86 years). The male-to-female ratio was 17:18. ECOG PS was 0 to 5 in 14.2% of patients; PS was 1 to 27 in 77.1% of patients; PS was 2 to 3 in 8.6% of patients. Stage IIIA:IIIB ratio was 22:13 (62.9%:37.1%). Of 37 patients, 2 (5.4%) failed to achieve EQD2 > 60 Gy. Median prescribed tumor dose was 77.4 Gy (range, 61.2-79.2 Gy). A maximum dose of 79.2Gy was achieved in 14 patients (37.8%). Grade 3 esophagitis was reported in 2 patients, and no patients developed grade 3 to 4 pneumonitis. There were 3 grade 5 events: acute radiation pneumonitis, bronchopulmonary hemorrhage, and acute lung infection. Median follow-up at time of analysis was 25.4 months (range, 8.0-44.2) months for 11 of 35 survivors. The median survival was 18.1 months (95% confidence interval [CI], 13.9-30.6), 2-year overall survival was 33.6% (95% CI, 17.9-50.1), and progression-free survival was 23.9% (95% CI, 11.3-39.1). Conclusions: Isotoxic IMRT is a well-tolerated and feasible approach to treatment intensification.",

keywords = "Radiotherapy, Isotoxic, Lung cancer, Non-small cell lung cancer (NSCLC), Dose Escalation, IMRT",

author = "Kate Haslett and Neil Bayman and Kevin Franks and Nicki Groom and Harden, {Susan V.} and Catherine Harris and Gerard Hanna and Stephen Harrow and Matthew Hatton and Paula McCloskey and Fiona McDonald and Ryder, {W. David} and Corinne Faivre-Finn",

note = "Funding Information: This research is jointly funded by Cancer Research UK's (CRUK) Clinical Trials Awards and Advisory Committee (CTAAC) & British Lung Foundation (grant reference number C17052/A15702). C.F-F. is supported by the NIHR Manchester Biomedical Research Center. Funding Information: The authors acknowledge the support of Damian Mullan and Ben Taylor (radiology input), Carl Rowbottom and Gareth Webster (protocol development), Dave Ardron (patient representative), Tsang Yatman/Elizabeth Miles/Romaana Mir (NCRI Radiation therapy Quality Assurance Group), Glenda Laviste (senior clinical trials nurse), Sally Falk (research project manager). Funding Information: This research is jointly funded by Cancer Research UK{\textquoteright}s (CRUK) Clinical Trials Awards and Advisory Committee (CTAAC) & British Lung Foundation (grant reference number C17052/A15702). C.F-F. is supported by the NIHR Manchester Biomedical Research Center. Publisher Copyright: {\textcopyright} 2020 The Authors",

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doi = "10.1016/j.ijrobp.2020.11.040",

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Haslett, K, Bayman, N, Franks, K, Groom, N, Harden, SV, Harris, C, Hanna, G, Harrow, S, Hatton, M, McCloskey, P, McDonald, F, Ryder, WD & Faivre-Finn, C 2021, 'Isotoxic Intensity Modulated Radiation Therapy in Stage III Non-Small Cell Lung Cancer: A Feasibility Study', International Journal of Radiation Oncology Biology Physics, vol. 109, no. 5, pp. 1341-1348. https://doi.org/10.1016/j.ijrobp.2020.11.040

TY - JOUR

T1 - Isotoxic Intensity Modulated Radiation Therapy in Stage III Non-Small Cell Lung Cancer: A Feasibility Study

AU - Haslett, Kate

AU - Bayman, Neil

AU - Franks, Kevin

AU - Groom, Nicki

AU - Harden, Susan V.

AU - Harris, Catherine

AU - Hanna, Gerard

AU - Harrow, Stephen

AU - Hatton, Matthew

AU - McCloskey, Paula

AU - McDonald, Fiona

AU - Ryder, W. David

AU - Faivre-Finn, Corinne

N1 - Funding Information: This research is jointly funded by Cancer Research UK's (CRUK) Clinical Trials Awards and Advisory Committee (CTAAC) & British Lung Foundation (grant reference number C17052/A15702). C.F-F. is supported by the NIHR Manchester Biomedical Research Center. Funding Information: The authors acknowledge the support of Damian Mullan and Ben Taylor (radiology input), Carl Rowbottom and Gareth Webster (protocol development), Dave Ardron (patient representative), Tsang Yatman/Elizabeth Miles/Romaana Mir (NCRI Radiation therapy Quality Assurance Group), Glenda Laviste (senior clinical trials nurse), Sally Falk (research project manager). Funding Information: This research is jointly funded by Cancer Research UK’s (CRUK) Clinical Trials Awards and Advisory Committee (CTAAC) & British Lung Foundation (grant reference number C17052/A15702). C.F-F. is supported by the NIHR Manchester Biomedical Research Center. Publisher Copyright: © 2020 The Authors

PY - 2021/4/1

Y1 - 2021/4/1

N2 - Purpose: Not all patients with stage III non-small cell lung cancer (NSCLC) are suitable for concurrent chemoradiation therapy (CRT). Local failure rate is high for sequential concurrent CRT. As such, there is a rationale for treatment intensification. Methods and Materials: Isotoxic intensity modulated radiation therapy (IMRT) is a multicenter feasibility study that combines different intensification strategies including hyperfractionation, acceleration, and dose escalation facilitated by IMRT. Patients with unresectable stage III NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and unsuitable for concurrent CRT were recruited. A minimum of 2 cycles of platinum-based chemotherapy was compulsory before starting radiation therapy (RT). Radiation dose was increased until a maximum dose of 79.2 Gy was reached or 1 or more of the organs at risk met predefined constraints. RT was delivered in 1.8-Gy fractions twice daily, and an RT quality assurance program was implemented. The primary objective was the delivery of isotoxic IMRT to a dose >60 Gy equivalent dose in 2-Gy fractions (EQD2 assuming an α/β ratio of 10 Gy for acute reacting tissues). Results: Thirty-seven patients were recruited from 7 UK centers. Median age was 69.9 years (range, 46-86 years). The male-to-female ratio was 17:18. ECOG PS was 0 to 5 in 14.2% of patients; PS was 1 to 27 in 77.1% of patients; PS was 2 to 3 in 8.6% of patients. Stage IIIA:IIIB ratio was 22:13 (62.9%:37.1%). Of 37 patients, 2 (5.4%) failed to achieve EQD2 > 60 Gy. Median prescribed tumor dose was 77.4 Gy (range, 61.2-79.2 Gy). A maximum dose of 79.2Gy was achieved in 14 patients (37.8%). Grade 3 esophagitis was reported in 2 patients, and no patients developed grade 3 to 4 pneumonitis. There were 3 grade 5 events: acute radiation pneumonitis, bronchopulmonary hemorrhage, and acute lung infection. Median follow-up at time of analysis was 25.4 months (range, 8.0-44.2) months for 11 of 35 survivors. The median survival was 18.1 months (95% confidence interval [CI], 13.9-30.6), 2-year overall survival was 33.6% (95% CI, 17.9-50.1), and progression-free survival was 23.9% (95% CI, 11.3-39.1). Conclusions: Isotoxic IMRT is a well-tolerated and feasible approach to treatment intensification.

AB - Purpose: Not all patients with stage III non-small cell lung cancer (NSCLC) are suitable for concurrent chemoradiation therapy (CRT). Local failure rate is high for sequential concurrent CRT. As such, there is a rationale for treatment intensification. Methods and Materials: Isotoxic intensity modulated radiation therapy (IMRT) is a multicenter feasibility study that combines different intensification strategies including hyperfractionation, acceleration, and dose escalation facilitated by IMRT. Patients with unresectable stage III NSCLC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 2, and unsuitable for concurrent CRT were recruited. A minimum of 2 cycles of platinum-based chemotherapy was compulsory before starting radiation therapy (RT). Radiation dose was increased until a maximum dose of 79.2 Gy was reached or 1 or more of the organs at risk met predefined constraints. RT was delivered in 1.8-Gy fractions twice daily, and an RT quality assurance program was implemented. The primary objective was the delivery of isotoxic IMRT to a dose >60 Gy equivalent dose in 2-Gy fractions (EQD2 assuming an α/β ratio of 10 Gy for acute reacting tissues). Results: Thirty-seven patients were recruited from 7 UK centers. Median age was 69.9 years (range, 46-86 years). The male-to-female ratio was 17:18. ECOG PS was 0 to 5 in 14.2% of patients; PS was 1 to 27 in 77.1% of patients; PS was 2 to 3 in 8.6% of patients. Stage IIIA:IIIB ratio was 22:13 (62.9%:37.1%). Of 37 patients, 2 (5.4%) failed to achieve EQD2 > 60 Gy. Median prescribed tumor dose was 77.4 Gy (range, 61.2-79.2 Gy). A maximum dose of 79.2Gy was achieved in 14 patients (37.8%). Grade 3 esophagitis was reported in 2 patients, and no patients developed grade 3 to 4 pneumonitis. There were 3 grade 5 events: acute radiation pneumonitis, bronchopulmonary hemorrhage, and acute lung infection. Median follow-up at time of analysis was 25.4 months (range, 8.0-44.2) months for 11 of 35 survivors. The median survival was 18.1 months (95% confidence interval [CI], 13.9-30.6), 2-year overall survival was 33.6% (95% CI, 17.9-50.1), and progression-free survival was 23.9% (95% CI, 11.3-39.1). Conclusions: Isotoxic IMRT is a well-tolerated and feasible approach to treatment intensification.

KW - Radiotherapy

KW - Isotoxic

KW - Lung cancer

KW - Non-small cell lung cancer (NSCLC)

KW - Dose Escalation

KW - IMRT

U2 - 10.1016/j.ijrobp.2020.11.040

DO - 10.1016/j.ijrobp.2020.11.040

M3 - Article

C2 - 33232772

AN - SCOPUS:85098210583

SN - 0360-3016

VL - 109

SP - 1341

EP - 1348

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

IS - 5

ER -

Isotoxic Intensity Modulated Radiation Therapy in Stage III Non-Small Cell Lung Cancer: A Feasibility Study

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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