Risk factors for cognitive impairment in radically treated stage III NSCLC : Secondary findings of the NVALT-11 study

H.Y. Zeng; L.E.L. Hendriks; W.J.A. Witlox; H.J.M. Groen; A.M.C. Dingemans; J. Praag; J. Belderbos; R. Houben; V. van der Noort; D.K.M. De Ruysscher

doi:10.1016/j.radonc.2023.109627

Risk factors for cognitive impairment in radically treated stage III NSCLC : Secondary findings of the NVALT-11 study

H.Y. Zeng^*
, L.E.L. Hendriks
, W.J.A. Witlox
, H.J.M. Groen
, A.M.C. Dingemans
, J. Praag
, J. Belderbos
, R. Houben
, V. van der Noort
, D.K.M. De Ruysscher

^*Corresponding author for this work

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

Abstract

Aim: To identify risk factors for self-reported cognitive impairment in radically treated stage III non-small cell lung cancer (NSCLC). Methods: Cognitive functioning was assessed using the EORTC-QLQ-C30 at seven pre-specified time points in the phase III NVALT-11 trial (observation versus prophylactic cranial irradiation [PCI] in stage III NSCLC treated with chemo-radiotherapy +/- surgery). Cognition was analyzed as binary (impairment or not) and continuous outcome, respectively, using generalized estimating equation (GEE) before and after multiple imputation. A score < 75 was defined as cognitive impairment. A mean difference by < 10, 10-<20, >= 20 points was regarded as of no, moderate, and large clinical effect, respectively. We categorized the cognitive impairment into four types based on changes over time: sustained, rever-sible, recurring, and alternating. Results: In the no-PCI arm, 43/84 [51.2%] reported cognitive impairment at least once, of which 31.4% were sustained, 25.7% reversible, 28.6% recurring, and 14.3% alternating. Results were similar in the PCI arm. Cognitive functioning at baseline was comparable in two arms and a score < 75 was a significant risk factor with large effect for subsequent cognitive impairment (no-PCI: p = -23.30, p < 0.001; PCI arm: p = -22.34, p < 0.001; All: p = -23.47, p < 0.001). Younger age (<60y), squamous histology, and PCI were risk factors without clinical relevance (p >-10, p < 0.05). Cognitive functioning declined over time (p = -0.26, p = 0.001) except for patients with cognitive impairment at baseline (p = 0.141, p = 0.33). Conclusion: Cognitive impairment is dynamic over time with four types. Baseline cognitive impairment (score < 75) is the most important risk factor for subsequent cognitive impairment in stage III NSCLC. Note: This work has been partly reported as an oral presentation at the ESTRO 2021 meeting (OC-0176). (c) 2023 Elsevier B.V. All rights reserved. Radiotherapy and Oncology xxx (2023) xxx-xxx

Original language	English
Article number	109627
Number of pages	10
Journal	Radiotherapy and Oncology
Volume	183
Issue number	1
DOIs	https://doi.org/10.1016/j.radonc.2023.109627
Publication status	Published - 1 Jun 2023

Keywords

Cognitive impairment
Non-small cell lung cancer (NSCLC)
Multi-modality treatment
Concurrent chemo-radiotherapy
Multiple imputation-generalized estimating
equation (MI-GEE)
PROPHYLACTIC CRANIAL IRRADIATION
QUALITY-OF-LIFE
WHOLE-BRAIN RADIOTHERAPY
RTOG 0212
ONCOLOGY
TRIAL
MEMANTINE
DECLINE
IMPACT

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Zeng, H. Y., Hendriks, L. E. L., Witlox, W. J. A., Groen, H. J. M., Dingemans, A. M. C., Praag, J., Belderbos, J., Houben, R., van der Noort, V., & De Ruysscher, D. K. M. (2023). Risk factors for cognitive impairment in radically treated stage III NSCLC : Secondary findings of the NVALT-11 study. Radiotherapy and Oncology, 183(1), Article 109627. https://doi.org/10.1016/j.radonc.2023.109627

@article{034dd514f62f41b4b8857ad216cb739c,

title = "Risk factors for cognitive impairment in radically treated stage III NSCLC : Secondary findings of the NVALT-11 study",

abstract = "Aim: To identify risk factors for self-reported cognitive impairment in radically treated stage III non-small cell lung cancer (NSCLC). Methods: Cognitive functioning was assessed using the EORTC-QLQ-C30 at seven pre-specified time points in the phase III NVALT-11 trial (observation versus prophylactic cranial irradiation [PCI] in stage III NSCLC treated with chemo-radiotherapy +/- surgery). Cognition was analyzed as binary (impairment or not) and continuous outcome, respectively, using generalized estimating equation (GEE) before and after multiple imputation. A score < 75 was defined as cognitive impairment. A mean difference by < 10, 10-<20, >= 20 points was regarded as of no, moderate, and large clinical effect, respectively. We categorized the cognitive impairment into four types based on changes over time: sustained, rever-sible, recurring, and alternating. Results: In the no-PCI arm, 43/84 [51.2\%] reported cognitive impairment at least once, of which 31.4\% were sustained, 25.7\% reversible, 28.6\% recurring, and 14.3\% alternating. Results were similar in the PCI arm. Cognitive functioning at baseline was comparable in two arms and a score < 75 was a significant risk factor with large effect for subsequent cognitive impairment (no-PCI: p = -23.30, p < 0.001; PCI arm: p = -22.34, p < 0.001; All: p = -23.47, p < 0.001). Younger age (<60y), squamous histology, and PCI were risk factors without clinical relevance (p >-10, p < 0.05). Cognitive functioning declined over time (p = -0.26, p = 0.001) except for patients with cognitive impairment at baseline (p = 0.141, p = 0.33). Conclusion: Cognitive impairment is dynamic over time with four types. Baseline cognitive impairment (score < 75) is the most important risk factor for subsequent cognitive impairment in stage III NSCLC. Note: This work has been partly reported as an oral presentation at the ESTRO 2021 meeting (OC-0176). (c) 2023 Elsevier B.V. All rights reserved. Radiotherapy and Oncology xxx (2023) xxx-xxx",

keywords = "Cognitive impairment, Non-small cell lung cancer (NSCLC), Multi-modality treatment, Concurrent chemo-radiotherapy, Multiple imputation-generalized estimating, equation (MI-GEE), PROPHYLACTIC CRANIAL IRRADIATION, QUALITY-OF-LIFE, WHOLE-BRAIN RADIOTHERAPY, RTOG 0212, ONCOLOGY, TRIAL, MEMANTINE, DECLINE, IMPACT",

author = "H.Y. Zeng and L.E.L. Hendriks and W.J.A. Witlox and H.J.M. Groen and A.M.C. Dingemans and J. Praag and J. Belderbos and R. Houben and \{van der Noort\}, V. and \{De Ruysscher\}, D.K.M.",

note = "Funding Information: We sincerely thank the following grant for supporting us to complete this study: Scholarship of China Scholarship Council (Grant No. : CSC 201909370087). We sincerely thank all the researchers of NVALT-11trial for their efforts to conduct this trial successfully and the patients to participate in this trial. Publisher Copyright: {\textcopyright} 2023 Elsevier B.V.",

year = "2023",

month = jun,

day = "1",

doi = "10.1016/j.radonc.2023.109627",

language = "English",

volume = "183",

journal = "Radiotherapy and Oncology",

issn = "0167-8140",

publisher = "Elsevier Ireland Ltd",

number = "1",

}

TY - JOUR

T1 - Risk factors for cognitive impairment in radically treated stage III NSCLC : Secondary findings of the NVALT-11 study

AU - Zeng, H.Y.

AU - Hendriks, L.E.L.

AU - Witlox, W.J.A.

AU - Groen, H.J.M.

AU - Dingemans, A.M.C.

AU - Praag, J.

AU - Belderbos, J.

AU - Houben, R.

AU - van der Noort, V.

AU - De Ruysscher, D.K.M.

N1 - Funding Information: We sincerely thank the following grant for supporting us to complete this study: Scholarship of China Scholarship Council (Grant No. : CSC 201909370087). We sincerely thank all the researchers of NVALT-11trial for their efforts to conduct this trial successfully and the patients to participate in this trial. Publisher Copyright: © 2023 Elsevier B.V.

PY - 2023/6/1

Y1 - 2023/6/1

N2 - Aim: To identify risk factors for self-reported cognitive impairment in radically treated stage III non-small cell lung cancer (NSCLC). Methods: Cognitive functioning was assessed using the EORTC-QLQ-C30 at seven pre-specified time points in the phase III NVALT-11 trial (observation versus prophylactic cranial irradiation [PCI] in stage III NSCLC treated with chemo-radiotherapy +/- surgery). Cognition was analyzed as binary (impairment or not) and continuous outcome, respectively, using generalized estimating equation (GEE) before and after multiple imputation. A score < 75 was defined as cognitive impairment. A mean difference by < 10, 10-<20, >= 20 points was regarded as of no, moderate, and large clinical effect, respectively. We categorized the cognitive impairment into four types based on changes over time: sustained, rever-sible, recurring, and alternating. Results: In the no-PCI arm, 43/84 [51.2%] reported cognitive impairment at least once, of which 31.4% were sustained, 25.7% reversible, 28.6% recurring, and 14.3% alternating. Results were similar in the PCI arm. Cognitive functioning at baseline was comparable in two arms and a score < 75 was a significant risk factor with large effect for subsequent cognitive impairment (no-PCI: p = -23.30, p < 0.001; PCI arm: p = -22.34, p < 0.001; All: p = -23.47, p < 0.001). Younger age (<60y), squamous histology, and PCI were risk factors without clinical relevance (p >-10, p < 0.05). Cognitive functioning declined over time (p = -0.26, p = 0.001) except for patients with cognitive impairment at baseline (p = 0.141, p = 0.33). Conclusion: Cognitive impairment is dynamic over time with four types. Baseline cognitive impairment (score < 75) is the most important risk factor for subsequent cognitive impairment in stage III NSCLC. Note: This work has been partly reported as an oral presentation at the ESTRO 2021 meeting (OC-0176). (c) 2023 Elsevier B.V. All rights reserved. Radiotherapy and Oncology xxx (2023) xxx-xxx

AB - Aim: To identify risk factors for self-reported cognitive impairment in radically treated stage III non-small cell lung cancer (NSCLC). Methods: Cognitive functioning was assessed using the EORTC-QLQ-C30 at seven pre-specified time points in the phase III NVALT-11 trial (observation versus prophylactic cranial irradiation [PCI] in stage III NSCLC treated with chemo-radiotherapy +/- surgery). Cognition was analyzed as binary (impairment or not) and continuous outcome, respectively, using generalized estimating equation (GEE) before and after multiple imputation. A score < 75 was defined as cognitive impairment. A mean difference by < 10, 10-<20, >= 20 points was regarded as of no, moderate, and large clinical effect, respectively. We categorized the cognitive impairment into four types based on changes over time: sustained, rever-sible, recurring, and alternating. Results: In the no-PCI arm, 43/84 [51.2%] reported cognitive impairment at least once, of which 31.4% were sustained, 25.7% reversible, 28.6% recurring, and 14.3% alternating. Results were similar in the PCI arm. Cognitive functioning at baseline was comparable in two arms and a score < 75 was a significant risk factor with large effect for subsequent cognitive impairment (no-PCI: p = -23.30, p < 0.001; PCI arm: p = -22.34, p < 0.001; All: p = -23.47, p < 0.001). Younger age (<60y), squamous histology, and PCI were risk factors without clinical relevance (p >-10, p < 0.05). Cognitive functioning declined over time (p = -0.26, p = 0.001) except for patients with cognitive impairment at baseline (p = 0.141, p = 0.33). Conclusion: Cognitive impairment is dynamic over time with four types. Baseline cognitive impairment (score < 75) is the most important risk factor for subsequent cognitive impairment in stage III NSCLC. Note: This work has been partly reported as an oral presentation at the ESTRO 2021 meeting (OC-0176). (c) 2023 Elsevier B.V. All rights reserved. Radiotherapy and Oncology xxx (2023) xxx-xxx

KW - Cognitive impairment

KW - Non-small cell lung cancer (NSCLC)

KW - Multi-modality treatment

KW - Concurrent chemo-radiotherapy

KW - Multiple imputation-generalized estimating

KW - equation (MI-GEE)

KW - PROPHYLACTIC CRANIAL IRRADIATION

KW - QUALITY-OF-LIFE

KW - WHOLE-BRAIN RADIOTHERAPY

KW - RTOG 0212

KW - ONCOLOGY

KW - TRIAL

KW - MEMANTINE

KW - DECLINE

KW - IMPACT

U2 - 10.1016/j.radonc.2023.109627

DO - 10.1016/j.radonc.2023.109627

M3 - Article

C2 - 36934893

SN - 0167-8140

VL - 183

JO - Radiotherapy and Oncology

JF - Radiotherapy and Oncology

IS - 1

M1 - 109627

ER -

Risk factors for cognitive impairment in radically treated stage III NSCLC : Secondary findings of the NVALT-11 study

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Keywords

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