The association between skeletal muscle measures and chemotherapy-induced toxicity in non-small cell lung cancer patients (2024)

de Jong, C., Chargi, N., Herder, G. J. M., van Haarlem, S. W. A., van der Meer, F., van Lindert, A. S. R., Ten Heuvel, A., Brouwer, J., de Jong, P. A., Devriese, L. A., Huitema, A. D. R., Egberts, T. C. G., de Bree, R. (2022). The association between skeletal muscle measures and chemotherapy-induced toxicity in non-small cell lung cancer patients. Journal of Cachexia, Sarcopenia and Muscle, 13(3), 1554-1564. https://doi.org/10.1002/jcsm.12967

de Jong, Corine ; Chargi, Najiba ; Herder, Gerarda J M et al. / The association between skeletal muscle measures and chemotherapy-induced toxicity in non-small cell lung cancer patients. In: Journal of Cachexia, Sarcopenia and Muscle. 2022 ; Vol. 13, No. 3. pp. 1554-1564.

@article{3019a57f65d445239e7aaf4f5bfbfe7e,

title = "The association between skeletal muscle measures and chemotherapy-induced toxicity in non-small cell lung cancer patients",

abstract = "BACKGROUND: Chemotherapy-induced toxicities frequently occur in non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Low skeletal muscle mass (SMM) has been associated with a higher incidence of toxicities for several types of cancers and cytostatics. The aim of this study was to evaluate the association between skeletal muscle measures and chemotherapy-induced toxicity in a large cohort of NSCLC patients.METHODS: A multicentre prospective follow-up study (PGxLUNG, NTR number NL5373610015) in NSCLC patients was conducted. Included were patients diagnosed with NSCLC (stage II-IV) treated with first-line platinum-based (cisplatin or carboplatin) chemotherapy of whom pretreatment imaging was available. Skeletal muscle area (SMA) segmentation was performed on abdominal imaging at the level of the third lumbar vertebra (L3). SMA at the level of L3 was corrected for squared height (m2 ) to yield the lumbar skeletal muscle mass index (LSMI). Skeletal muscle density (SMD) was calculated as the mean Hounsfield Unit (HU) of the segmented SMA. SMM and SMD were categorized as low, intermediate, and high, based on LSMI and mean HU tertiles, respectively. Chemotherapy-induced toxicity was scored using CTCAE v4.03 and categorized into haematological (anaemia, leukocytopenia, neutropenia, and thrombocytopenia), non-haematological (nephrotoxicity, neurotoxicity, and esophagitis), and dose-limiting toxicity (DLT) (treatment switch, delay, de-escalation, discontinuation, or hospitalization). The relationship between SMM, SMD, and toxicities was assessed with logistic regression modelling taking into account potential confounders like gender and body mass index (BMI).RESULTS: In total, 297 patients (male n = 167, median age 64 years) were included. Haematological toxicity grade 3/4 was experienced in 36.6% (n = 108) of the patients, 24.6% (n = 73) experienced any non-haematological toxicity grade ≥2, and 55.6% (n = 165) any DLT. Multivariate logistic regression analysis showed that low SMM (ORadj 2.41, 95% CI 1.31-4.45, P = 0.005) and age at diagnosis >65 years (ORadj 1.76, 95% CI 1.07-2.90, P = 0.025) were statistically significantly associated with overall haematological toxicity grade 3/4. No statistically significant associations were found between low SMM or low SMD and non-haematological toxicities. Low SMM (ORadj 2.23, 95% CI 1.23-4.04, P = 0.008) and high SMD (ORadj 0.41, 95% CI 0.23-0.74, P = 0.003) were statistically significantly associated with a higher respectively lower risk of DLT.CONCLUSIONS: Non-small cell lung cancer patients with pretreatment low SMM are at significant higher risk for haematological toxicities grade 3/4 and DLT. NSCLC patients with high SMD are at significant lower risk for DLT. Further studies should be aimed to investigate whether platinum dosing based on skeletal muscle measurements and/or improvement of pretreatment SMM/SMD could reduce the risk of toxicity without compromising efficacy.",

keywords = "Body composition, Chemotherapy-induced toxicity, Non-small cell lung cancer, Platinum-based chemotherapy, Skeletal muscle mass",

author = "{de Jong}, Corine and Najiba Chargi and Herder, {Gerarda J M} and {van Haarlem}, {Simone W A} and {van der Meer}, Femke and {van Lindert}, {Anne S R} and {Ten Heuvel}, Alexandra and Jan Brouwer and {de Jong}, {Pim A} and Devriese, {Lot A} and Huitema, {Alwin D R} and Egberts, {Toine C G} and {de Bree}, Remco and Deneer, {Vera H M}",

note = "Funding Information: The PGxLUNG study was funded by the St. Antonius Onderzoeksfonds and patient funding. Financial support for the genotyping (data not used in this study) was provided by Roche Nederland B.V. The funding sources had no role in study design, data collection, data analysis, data interpretation, or the writing of the report. The authors would like to thank Dr. J. Lavalaye (Department of Nuclear Medicine, St. Antonius Hospital, Nieuwegein, the Netherlands), Dr. P. J. Hagen (Department of Nuclear Medicine, Diakonessen Hospital, Utrecht, the Netherlands), Drs. J. P. Esser (Department of Nuclear Medicine, Meander Medical Center, the Netherlands), and Drs. H. Adams (Department of Nuclear Medicine, Groene Hart Hospital, Gouda, the Netherlands) for providing the CT scans. Funding Information: The PGxLUNG study was funded by the St. Antonius Onderzoeksfonds and patient funding. Financial support for the genotyping (data not used in this study) was provided by Roche Nederland B.V. The funding sources had no role in study design, data collection, data analysis, data interpretation, or the writing of the report. Publisher Copyright: {\textcopyright} 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.",

year = "2022",

month = jun,

doi = "10.1002/jcsm.12967",

language = "English",

volume = "13",

pages = "1554--1564",

journal = "Journal of Cachexia, Sarcopenia and Muscle",

issn = "2190-5991",

publisher = "Wiley-Blackwell",

number = "3",

}

de Jong, C, Chargi, N, Herder, GJM, van Haarlem, SWA, van der Meer, F, van Lindert, ASR, Ten Heuvel, A, Brouwer, J, de Jong, PA, Devriese, LA, Huitema, ADR, Egberts, TCG, de Bree, R 2022, 'The association between skeletal muscle measures and chemotherapy-induced toxicity in non-small cell lung cancer patients', Journal of Cachexia, Sarcopenia and Muscle, vol. 13, no. 3, pp. 1554-1564. https://doi.org/10.1002/jcsm.12967

The association between skeletal muscle measures and chemotherapy-induced toxicity in non-small cell lung cancer patients. / de Jong, Corine; Chargi, Najiba; Herder, Gerarda J M et al.
In: Journal of Cachexia, Sarcopenia and Muscle, Vol. 13, No. 3, 06.2022, p. 1554-1564.

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

TY - JOUR

T1 - The association between skeletal muscle measures and chemotherapy-induced toxicity in non-small cell lung cancer patients

AU - de Jong, Corine

AU - Chargi, Najiba

AU - Herder, Gerarda J M

AU - van Haarlem, Simone W A

AU - van der Meer, Femke

AU - van Lindert, Anne S R

AU - Ten Heuvel, Alexandra

AU - Brouwer, Jan

AU - de Jong, Pim A

AU - Devriese, Lot A

AU - Huitema, Alwin D R

AU - Egberts, Toine C G

AU - de Bree, Remco

AU - Deneer, Vera H M

N1 - Funding Information:The PGxLUNG study was funded by the St. Antonius Onderzoeksfonds and patient funding. Financial support for the genotyping (data not used in this study) was provided by Roche Nederland B.V. The funding sources had no role in study design, data collection, data analysis, data interpretation, or the writing of the report. The authors would like to thank Dr. J. Lavalaye (Department of Nuclear Medicine, St. Antonius Hospital, Nieuwegein, the Netherlands), Dr. P. J. Hagen (Department of Nuclear Medicine, Diakonessen Hospital, Utrecht, the Netherlands), Drs. J. P. Esser (Department of Nuclear Medicine, Meander Medical Center, the Netherlands), and Drs. H. Adams (Department of Nuclear Medicine, Groene Hart Hospital, Gouda, the Netherlands) for providing the CT scans.Funding Information:The PGxLUNG study was funded by the St. Antonius Onderzoeksfonds and patient funding. Financial support for the genotyping (data not used in this study) was provided by Roche Nederland B.V. The funding sources had no role in study design, data collection, data analysis, data interpretation, or the writing of the report.Publisher Copyright:© 2022 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.

PY - 2022/6

Y1 - 2022/6

N2 - BACKGROUND: Chemotherapy-induced toxicities frequently occur in non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Low skeletal muscle mass (SMM) has been associated with a higher incidence of toxicities for several types of cancers and cytostatics. The aim of this study was to evaluate the association between skeletal muscle measures and chemotherapy-induced toxicity in a large cohort of NSCLC patients.METHODS: A multicentre prospective follow-up study (PGxLUNG, NTR number NL5373610015) in NSCLC patients was conducted. Included were patients diagnosed with NSCLC (stage II-IV) treated with first-line platinum-based (cisplatin or carboplatin) chemotherapy of whom pretreatment imaging was available. Skeletal muscle area (SMA) segmentation was performed on abdominal imaging at the level of the third lumbar vertebra (L3). SMA at the level of L3 was corrected for squared height (m2 ) to yield the lumbar skeletal muscle mass index (LSMI). Skeletal muscle density (SMD) was calculated as the mean Hounsfield Unit (HU) of the segmented SMA. SMM and SMD were categorized as low, intermediate, and high, based on LSMI and mean HU tertiles, respectively. Chemotherapy-induced toxicity was scored using CTCAE v4.03 and categorized into haematological (anaemia, leukocytopenia, neutropenia, and thrombocytopenia), non-haematological (nephrotoxicity, neurotoxicity, and esophagitis), and dose-limiting toxicity (DLT) (treatment switch, delay, de-escalation, discontinuation, or hospitalization). The relationship between SMM, SMD, and toxicities was assessed with logistic regression modelling taking into account potential confounders like gender and body mass index (BMI).RESULTS: In total, 297 patients (male n = 167, median age 64 years) were included. Haematological toxicity grade 3/4 was experienced in 36.6% (n = 108) of the patients, 24.6% (n = 73) experienced any non-haematological toxicity grade ≥2, and 55.6% (n = 165) any DLT. Multivariate logistic regression analysis showed that low SMM (ORadj 2.41, 95% CI 1.31-4.45, P = 0.005) and age at diagnosis >65 years (ORadj 1.76, 95% CI 1.07-2.90, P = 0.025) were statistically significantly associated with overall haematological toxicity grade 3/4. No statistically significant associations were found between low SMM or low SMD and non-haematological toxicities. Low SMM (ORadj 2.23, 95% CI 1.23-4.04, P = 0.008) and high SMD (ORadj 0.41, 95% CI 0.23-0.74, P = 0.003) were statistically significantly associated with a higher respectively lower risk of DLT.CONCLUSIONS: Non-small cell lung cancer patients with pretreatment low SMM are at significant higher risk for haematological toxicities grade 3/4 and DLT. NSCLC patients with high SMD are at significant lower risk for DLT. Further studies should be aimed to investigate whether platinum dosing based on skeletal muscle measurements and/or improvement of pretreatment SMM/SMD could reduce the risk of toxicity without compromising efficacy.

AB - BACKGROUND: Chemotherapy-induced toxicities frequently occur in non-small cell lung cancer (NSCLC) patients treated with platinum-based chemotherapy. Low skeletal muscle mass (SMM) has been associated with a higher incidence of toxicities for several types of cancers and cytostatics. The aim of this study was to evaluate the association between skeletal muscle measures and chemotherapy-induced toxicity in a large cohort of NSCLC patients.METHODS: A multicentre prospective follow-up study (PGxLUNG, NTR number NL5373610015) in NSCLC patients was conducted. Included were patients diagnosed with NSCLC (stage II-IV) treated with first-line platinum-based (cisplatin or carboplatin) chemotherapy of whom pretreatment imaging was available. Skeletal muscle area (SMA) segmentation was performed on abdominal imaging at the level of the third lumbar vertebra (L3). SMA at the level of L3 was corrected for squared height (m2 ) to yield the lumbar skeletal muscle mass index (LSMI). Skeletal muscle density (SMD) was calculated as the mean Hounsfield Unit (HU) of the segmented SMA. SMM and SMD were categorized as low, intermediate, and high, based on LSMI and mean HU tertiles, respectively. Chemotherapy-induced toxicity was scored using CTCAE v4.03 and categorized into haematological (anaemia, leukocytopenia, neutropenia, and thrombocytopenia), non-haematological (nephrotoxicity, neurotoxicity, and esophagitis), and dose-limiting toxicity (DLT) (treatment switch, delay, de-escalation, discontinuation, or hospitalization). The relationship between SMM, SMD, and toxicities was assessed with logistic regression modelling taking into account potential confounders like gender and body mass index (BMI).RESULTS: In total, 297 patients (male n = 167, median age 64 years) were included. Haematological toxicity grade 3/4 was experienced in 36.6% (n = 108) of the patients, 24.6% (n = 73) experienced any non-haematological toxicity grade ≥2, and 55.6% (n = 165) any DLT. Multivariate logistic regression analysis showed that low SMM (ORadj 2.41, 95% CI 1.31-4.45, P = 0.005) and age at diagnosis >65 years (ORadj 1.76, 95% CI 1.07-2.90, P = 0.025) were statistically significantly associated with overall haematological toxicity grade 3/4. No statistically significant associations were found between low SMM or low SMD and non-haematological toxicities. Low SMM (ORadj 2.23, 95% CI 1.23-4.04, P = 0.008) and high SMD (ORadj 0.41, 95% CI 0.23-0.74, P = 0.003) were statistically significantly associated with a higher respectively lower risk of DLT.CONCLUSIONS: Non-small cell lung cancer patients with pretreatment low SMM are at significant higher risk for haematological toxicities grade 3/4 and DLT. NSCLC patients with high SMD are at significant lower risk for DLT. Further studies should be aimed to investigate whether platinum dosing based on skeletal muscle measurements and/or improvement of pretreatment SMM/SMD could reduce the risk of toxicity without compromising efficacy.

KW - Body composition

KW - Chemotherapy-induced toxicity

KW - Non-small cell lung cancer

KW - Platinum-based chemotherapy

KW - Skeletal muscle mass

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U2 - 10.1002/jcsm.12967

DO - 10.1002/jcsm.12967

M3 - Article

C2 - 35301821

SN - 2190-5991

VL - 13

SP - 1554

EP - 1564

JO - Journal of Cachexia, Sarcopenia and Muscle

JF - Journal of Cachexia, Sarcopenia and Muscle

IS - 3

ER -

de Jong C, Chargi N, Herder GJM, van Haarlem SWA, van der Meer F, van Lindert ASR et al. The association between skeletal muscle measures and chemotherapy-induced toxicity in non-small cell lung cancer patients. Journal of Cachexia, Sarcopenia and Muscle. 2022 Jun;13(3):1554-1564. doi: 10.1002/jcsm.12967