Objective: Evaluate pretreatment sarcopenia and anemia as prognostic factors in women undergoing treatment for cervical cancer (CC) with concurrent chemoradiotherapy (CCRT). Methods: 151 women with CC were analysed in this cohort study.Pretreatment computed tomography (CT) images were analysed to assess skeletal muscle index (SMI). Hazard ratios (HR) and multivariate Cox proportional HR were used to analyse association between low SMI, age, body mass index (BMI), haemoglobin levels, histological type, and International Federation of Gynaecology and Obstetrics (FIGO) stage with PFS and OS. Results: A total of 151 patients were included, 53 (35.1%) presented pretreatment sarcopenia; 51 (34%) stage I/II and 100 (66%) stage III/IV. Among those patients in advanced stage (III/IV) 37 (70%) (p = 0.28) were sarcopenic at the beginning of treatment. Sarcopenia was associated with worse progression-free survival (PFS) and overall survival (OS) in our cohort [HR 0.97 (p = 0.01)] [HR 0.73 (p = 0.001)], as well as anemia [HR 0.73 (p = 0.001)] [HR 0.78 (p = 0.001)]. Linear regression models indicated that despite showing no association with age, neutrophil or platelet counts, sarcopenia was associated with pretreatment anemia levels (p = 0.01). After a multivariate analysis, only haemoglobin (anemia) and complete CCRT remained associated with PFS and OS. Sarcopenia and anemia were associated with worse PFS and OS in FIGO stage I/II. Conclusion: Pretreatment sarcopenia was significantly associated with low haemoglobin levels. Anemia and incomplete CCRT were independently associated with poor prognosis in women with CC. Pretreatment sarcopenia, as low SMI, was a predictor of poor prognostic in early stages of CC.
References
[1]
Sung, H., Ferlay, J., Siegel, R.L., Laversanne, M., Soerjomataram, I., Jemal, A., et al. (2021) Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71, 209-249. https://doi.org/10.3322/caac.21660
[2]
Bhatla, N., Aoki, D., Sharma, D.N. and Sankaranarayanan, R. (2021) Cancer of the Cervix Uteri: 2021 Update. International Journal of Gynecology & Obstetrics, 155, 28-44. https://doi.org/10.1002/ijgo.13865
[3]
Mohamud, A., Høgdall, C. and Schnack, T. (2022) Prognostic Value of the 2018 FIGO Staging System for Cervical Cancer. Gynecologic Oncology, 165, 506-513. https://doi.org/10.1016/j.ygyno.2022.02.017
[4]
Caro, J.J., Salas, M., Ward, A. and Goss, G. (2001) Anemia as an Independent Prognostic Factor for Survival in Patients with Cancer: A Systemic, Quantitative Review. Cancer, 91, 2214-2221. https://doi.org/10.1002/1097-0142(20010615)91:12<2214::AID-CNCR1251>3.0.CO;2-P
[5]
Varlotto, J. and Stevenson, M.A. (2005) Anemia, Tumor Hypoxemia, and the Cancer Patient. International Journal of Radiation Oncology, Biology, Physics, 63, 25-36. https://doi.org/10.1016/j.ijrobp.2005.04.049
[6]
Wang, H., Chen, W.-M., Zhou, Y.-H., Shi, J.-P., Huang, Y.-Q. and Wang, W.-J. (2020) Combined PLT and NE to Predict the Prognosis of Patients with Locally Advanced Cervical Cancer. Scientific Reports, 10, Article No. 11210. https://doi.org/10.1038/s41598-020-66387-x
[7]
Tseng, S.-H., Lee, W.-J., Peng, L.-N., Lin, M.-H. and Chen, L.-K. (2021) Associations between Hemoglobin Levels and Sarcopenia and Its Components: Results from the I-Lan Longitudinal Study. Experimental Gerontology, 150, Article 111379. https://doi.org/10.1016/j.exger.2021.111379
[8]
Maccio, A., Sanna, E., Neri, M., Oppi, S. and Madeddu, C. (2021) Cachexia as Evidence of the Mechanisms of Resistance and Tolerance during the Evolution of Cancer Disease. International Journal of Molecular Sciences, 22, Article 2890. https://doi.org/10.3390/ijms22062890
[9]
Madeddu, C., Mantovani, G., Gramignano, G., Astara, G. and Macciò, A. (2015) Muscle Wasting as Main Evidence of Energy Impairment in Cancer Cachexia: Future Therapeutic Approaches. Future Oncology, 11, 2697-2710. https://doi.org/10.2217/fon.15.195
[10]
Lee, J., Chang, C.-L., Lin, J.-B., Wu, M.-H., Sun, F.-J., Jan, Y.-T., et al. (2018) Skeletal Muscle Loss Is an Imaging Biomarker of Outcome after Definitive Chemoradiotherapy for Locally Advanced Cervical Cancer. Clinical Cancer Research, 24, 5028-5036. https://doi.org/10.1158/1078-0432.CCR-18-0788
[11]
Silva de Paula, N., de Aguiar Bruno, K., Azevedo Aredes, M. and Villaça Chaves, G. (2018) Sarcopenia and Skeletal Muscle Quality as Predictors of Postoperative Complication and Early Mortality in Gynecologic Cancer. International Journal of Gynecologic Cancer, 28, 412-420. https://doi.org/10.1097/IGC.0000000000001157
[12]
Pamoukdjian, F., Bouillet, T., Lévy, V., Soussan, M., Zelek, L. and Paillaud, E. (2018) Prevalence and Predictive Value of Pre-Therapeutic Sarcopenia in Cancer Patients: A Systematic Review. Clinical Nutrition, 37, 1101-1113. https://doi.org/10.1016/j.clnu.2017.07.010
[13]
Rinninella, E., Fagotti, A., Cintoni, M., Raoul, P., Scaletta, G., Scambia, G., et al. (2020) Skeletal Muscle Mass as a Prognostic Indicator of Outcomes in Ovarian Cancer: A Systematic Review and Meta-Analysis. International Journal of Gynecologic Cancer, 30, 654-663. https://doi.org/10.1136/ijgc-2020-001215
[14]
Lee, J., Lin, J.-B., Chen, T.-C., Jan, Y.-T., Sun, F.-J., Chen, Y.-J., et al. (2022) Progressive Skeletal Muscle Loss after Surgery and Adjuvant Radiotherapy Impact Survival Outcomes in Patients with Early Stage Cervical Cancer. Frontiers in Nutrition, 8, Article 773506. https://doi.org/10.3389/fnut.2021.773506
[15]
Sutton, E.H., Plyta, M., Fragkos, K. and Di Caro, S. (2022) Pre-Treatment Sarcopenic Assessments as a Prognostic Factor for Gynaecology Cancer Outcomes: Systematic Review and Meta-Analysis. European Journal of Clinical Nutrition, 76, 1513-1527. https://doi.org/10.1038/s41430-022-01085-7
[16]
Cruz-Jentoft, A.J., Baeyens, J.P., Bauer, J.M., Boirie, Y., Cederholm, T., Landi, F., et al. (2010) Sarcopenia: European Consensus on Definition and Diagnosis: Report of the European Working Group on Sarcopenia in Older People. Age and Ageing, 39, 412-423. https://doi.org/10.1093/ageing/afq034
[17]
Vangelov, B., Bauer, J., Kotevski, D. and Smee, R.I. (2022) The Use of Alternate Vertebral Levels to L3 in Computed Tomography Scans for Skeletal Muscle Mass Evaluation and Sarcopenia Assessment in Patients with Cancer: A Systematic Review. British Journal of Nutrition, 127, 722-735. https://doi.org/10.1017/S0007114521001446
[18]
Eisenhauer, E.A., Therasse, P., Bogaerts, J., Schwartz, L.H., Sargent, D., Ford, R., et al. (2009) New Response Evaluation Criteria in Solid Tumours: Revised RECIST Guideline (Version 1.1). European Journal of Cancer, 45, 228-247. https://doi.org/10.1016/j.ejca.2008.10.026
[19]
National Cancer Institute (U.S.) (2017) Common Terminology Criteria for Adverse Events: (CTCAE) Version 5. U.S. Department Of Health and Human Services, Washington, DC.
[20]
Avrutin, E., Moisey, L.L., Zhang, R., Khattab, J., Todd, E., Premji, T., et al. (2018) Clinically Practical Approach for Screening of Low Muscularity Using Electronic Linear Measures on Computed Tomography Images in Critically Ill Patients. Journal of Parenteral and Enteral Nutrition, 42, 885-891. https://doi.org/10.1002/jpen.1019
[21]
Mourtzakis, M., Prado, C.M.M., Lieffers, J.R., Reiman, T., McCargar, L.J. and Baracos, V.E. (2008) A Practical and Precise Approach to Quantification of Body Composition in Cancer Patients Using Computed Tomography Images Acquired during Routine Care. Applied Physiology, Nutrition, and Metabolism, 33, 997-1006. https://doi.org/10.1139/H08-075
[22]
Wassie, M., Aemro, A. and Fentie, B. (2021) Prevalence and Associated Factors of Baseline Anemia among Cervical Cancer Patients in Tikur Anbesa Specialized Hospital, Ethiopia. BMC Women’s Health, 21, Article No. 36. https://doi.org/10.1186/s12905-021-01185-9
[23]
Xia, Y., Jiang, L. and Zhong, T. (2018) The Role of HIF-1α in Chemo-/Radioresistant Tumors. OncoTargets and Therapy, 11, 3003-3011. https://doi.org/10.2147/OTT.S158206
[24]
Zuliani, A.C., Esteves, S.C., Teixeira, L.C., Teixeira, J.C., De Souza, G.A. and Sarian, L.O. (2014) Concomitant Cisplatin Plus Radiotherapy and High-Dose-Rate Brachytherapy versus Radiotherapy Alone for Stage IIIB Epidermoid Cervical Cancer: A Randomized Controlled Trial. Journal of Clinical Oncology, 32, 542-547. https://doi.org/10.1200/JCO.2013.50.1205
[25]
Matsuoka, H., Nakamura, K., Matsubara, Y., Ida, N., Nishida, T., Ogawa, C., et al. (2019) Sarcopenia Is Not a Prognostic Factor of Outcome in Patients with Cervical Cancer Undergoing Concurrent Chemoradiotherapy or Radiotherapy. Anticancer Research, 39, 933-939. https://doi.org/10.21873/anticanres.13196
[26]
Yoshikawa, N., Shirakawa, A., Yoshida, K., Tamauchi, S., Suzuki, S., Kikkawa, F., et al. (2020) Sarcopenia as a Predictor of Survival among Patients with Organ Metastatic Cervical Cancer. Nutrition in Clinical Practice, 35, 1041-1046. https://doi.org/10.1002/ncp.10482
[27]
Han, Q., Kim, S.I., Yoon, S.H., Kim, T.M., Kang, H.C., Kim, H.J., et al. (2021) Impact of Computed Tomography-Based, Artificial Intelligence-Driven Volumetric Sarcopenia on Survival Outcomes in Early Cervical Cancer. Frontiers in Oncology, 11, Article 741071. https://doi.org/10.3389/fonc.2021.741071
[28]
Aichi, M., Hasegawa, S., Kurita, Y., Shinoda, S., Kato, S., Mizushima, T., et al. (2023) Low Skeletal Muscle Mass Predicts Poor Prognosis for Patients with Stage III Cervical Cancer on Concurrent Chemoradiotherapy. Nutrition, 109, Article 111966. https://doi.org/10.1016/j.nut.2022.111966
[29]
Petrelli, F., De Stefani, A., Raspagliesi, F., Lorusso, D. and Barni, S. (2014) Radiotherapy with Concurrent Cisplatin-Based Doublet or Weekly Cisplatin for Cervical Cancer: A Systematic Review and Meta-Analysis. Gynecologic Oncology, 134, 166-171. https://doi.org/10.1016/j.ygyno.2014.04.049
[30]
Uppal, S., Chapman, C., Spencer, R.J., Jolly, S., Maturen, K., Rauh-Hain, J.A., et al. (2017) Association of Hospital Volume with Racial and Ethnic Disparities in Locally Advanced Cervical Cancer Treatment. Obstetrics & Gynecology, 129, 295-304. https://doi.org/10.1097/AOG.0000000000001819
