Significance of the neutrophil-tolymphocyte ratio in predicting the response to neoadjuvant chemotherapy in extremity osteosarcoma: A multicentre retrospective study

- Significance of the neutrophil-to-.
- lymphocyte ratio in predicting the response to neoadjuvant chemotherapy in extremity.
- The purpose of this study was to investigate the significance of the neutrophil-to-lympho- cyte ratio (NLR) in predicting the response to NACT in extremity osteosarcoma..
- Methods: Pathological complete response (pCR) was used to assess the efficacy of NACT.
- Receiver operating char- acteristic (ROC) curves and the Youden index (sensitivity + specificity-1) were used to determine the optimal cut-off values of the NLR.
- Univariate and multivariate analyses using logistic regression models were conducted to confirm the independent factors affecting the efficacy of NACT..
- Univariate analysis revealed that patients with a smaller tumour volume, lower stage, lower NLR and lower PLR were more likely to achieve pCR..
- Multivariate analyses confirmed that the NLR before treatment was an independent risk factor for pCR.
- Compared to patients with a high NLR, those with a low NLR showed a more than 2-fold higher likelihood of achieving pCR (OR 2.82, 95% CI p = 0.02)..
- Conclusion: The NLR is a novel and effective predictive factor for the response to NACT in extremity osteosarcoma patients.
- Patients with a higher NLR showed a lower percentage of pCR after NACT..
- Keywords: Neutrophil-to-lymphocyte, Neoadjuvant chemotherapy, Osteosarcoma.
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- Osteosarcoma, which originates from mesenchymal tis- sue and is mainly located in the long bones, is one of the most common primary malignant tumours in children.
- However, the prognosis of patients treated with this combination was extremely poor, and the 5-year survival rate was approximately 42% [2].
- 1 Department of Orthopaedics, Minzu Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, China.
- 6 Department of Spine and Osteopathic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China Full list of author information is available at the end of the article.
- Hence, predicting the efficacy of NACT before surgery is very important.
- The neutrophil-to- lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are two important indices that reflect the SIR [11].
- Thus, we conducted this multicentre retrospective study to determine whether the NLR or PLR can be used to predict pCR after NACT in osteosarcoma and there- fore serve as a parameter to guide chemotherapy and sur- gical planning.
- To the best of our knowledge, this study is the first to explore the association of the response to NACT with the NLR and PLR in osteosarcoma..
- (3) patients with complete laboratory data before NACT;.
- and (5) patients with lesions located in the extremities.
- (1) patients with infection, fever, or any blood disease.
- (2) patients with recurrence.
- and (3) patients with incom- plete medical records..
- The clinical and pathological stages of the tumours were defined using the Enneking classification [16]..
- The NLR was calculated from routine peripheral blood examination results and defined as the absolute num- ber of neutrophils divided by the lymphocyte count.
- The same formula was applied to determine the platelet-to- lymphocyte ratio (PLR).
- The speci- men was cut along the cross section with the largest area according to the preoperative imaging.
- All patients received first-line NACT, and the detailed regimens were AP: doxorubicin 45 mg/m 2 + cispl- atin 75 ~ 100 mg/m 2 and MAP: high-dose methotrex- ate 8 ~ 12 g/m2 + doxorubicin 45 mg/m 2 + cisplatin 75 ~ 100 mg/m 2.
- The mean ± standard error and the median were used to present measurement data following a normal distribu- tion and a skewed distribution, respectively.
- A receiver operating characteristic (ROC) curve and the Youden index (sensitivity + specificity-1) were used to determine the optimal cut-off values of the NLR due to the lack of a reference value in recent literature..
- Baseline data of the patients and tumours.
- A total of 403 patients histopathologically diagnosed with osteosarcoma of the extremities were identified..
- male, and the median age at diagnosis was 17 years (range 7-45 years).
- Eighty-four (87.5%) tumours were located in the proximal tibia and distal femur, while 12 were located in other regions, including the proximal humerus, proxi- mal fibula and distal tibia.
- According to the Enneking surgical staging criteria, 28 patients were clas- sified as stage I, 46 as stage II, and 22 as stage III..
- The optimal cut‑off values of the NLR and PLR.
- 1, when pCR was defined as an end point, the areas under the curve (AUCs) for the NLR and PLR were 0.793 (p = 0.001) and 0.659 (p = 0.069), respectively.
- The optimal cut-off values of the NLR and PLR were 2.36 (sensitivity, 80.0%.
- Subsequently, according to the optimal cut-off values of the NLR, patients were divided into two groups: the low NLR group (LNLR <2.36) with 50 patients and the high NLR group (HNLR ≥2.36) with 46 patients.
- Similarly, 66 patients were included in the low PLR group (LPLR.
- <115), and 30 patients were included in the high PLR group (HPLR≥115)..
- Associations of the NLR and PLR with clinical parameters To investigate the relationships of the NLR and PLR with clinical parameters in osteosarcoma patients, com- parisons between the LNLR (LPLR) and HNLR (HPLR) groups were conducted (Table 1).
- Our results demon- strated that the tumour size in patients with a low NLR was significantly smaller than that in patients with a high NLR cm 3 vs.
- A similar result was found in the PLR group cm 3 vs.
- Additionally, an advanced Enneking stage and elevated ALP were significantly associated with a high NLR, while the rates of these two parameters were not significantly different in the PLR group..
- Our results revealed that patients with a smaller tumour volume, lower stage, lower NLR and lower PLR were more likely to achieve pCR.
- Subsequently, tumour size, Enneking stage, the NLR and the PLR were included in multivariate analyses.
- As shown in Table 3, the NLR before treatment was an independent risk factor for pCR..
- 1 The areas under the ROC curves and the optimal cut-off values of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR).
- Regimens of NACT 0.261.
- In this multicentre study, we explored the predic- tive value of the NLR for the effectiveness of NACT in patients with osteosarcoma of the extremities.
- Ninety-six patients undergoing NACT treatment were included, and the NLR and PLR were calculated.
- We found that a low pretreatment NLR (<2.36) was significantly associated with a higher rate of pCR and a better effect of NACT..
- However, other clinical parameters, including age, sex, tumour location, tumour size, clinical stage, tumour sub- type, ALP, the ESR, CRP and the PLR, presented no rel- evance to pCR in our study..
- Recently, many studies have demonstrated that the NLR plays a key role in predicting the treatment response to NACT and the survival rate in various cancers, such as colorectal cancer, rectal cancer, and breast cancer [17–21].
- In a recent study by Chae and his colleague [22], the data of 87 patients with breast cancer were ret- rospectively analysed.
- They found that patients in the low NLR group had a higher rate of pCR than those in the high NLR group (42.1% vs.
- [8] used the pretreatment NLR and PLR as prognostic indicators of pCR in patients with gastric cancer.
- The associations between an elevated NLR and an incomplete response and a poor prognosis in cancer are complex.
- First, inflammatory cells in the tumour microenvironment can secrete a.
- Neutro- phils and lymphocytes are the most important cells in the inflammatory reaction and contribute to inflamma- tion in the tumour microenvironment.
- Therefore, a higher NLR corresponds to a worse effect of NACT and a lower incidence of pCR..
- Meanwhile, this is a retrospective analy- sis, which may bring potential bias to the results.
- Our findings suggest that the NLR is an important fac- tor predicting the response to NACT in extremity osteo- sarcoma patients.
- NLR: Neutrophil-to-lymphocyte ratio;.
- PLR: Platelet-to-lymphocyte ratio.
- The authors would like to thank all the staff of the participating departments..
- This study has been supported by the Natural Science Foundation of Guangxi Province (grant no.
- 2020GXNSFAA259088), the “Medical Excellence Award” Funded by the Creative Research Development Grant from the First Affiliated Hospital of Guangxi Medical University, and the Youth Science and Technology Project of the First Affiliated Hospital of Guangxi Medical University (grant no.
- The funding source played no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript..
- All the data needed to achieve the conclusion are presented in the paper..
- The study was approved by the Institutional Review Board (IRB) of Minzu Hospital of Guangxi Zhuang Autonomous Region, the First Affiliated Hospital of Guangxi Medical University and Affiliated Tumor Hospital of Guangxi Medical University.
- The need for informed consent was waived by IRB of Minzu Hospital of Guangxi Zhuang Autonomous Region, the First Affiliated Hospital of Guangxi Medical University and Affiliated Tumor Hospital of Guangxi Medical University because of the retrospective nature of the study.
- 1 Department of Orthopaedics, Minzu Hospital of Guangxi Zhuang Autono- mous Region, Nanning, Guangxi, China.
- 2 People’s Hospital of Baise, Baise, Guangxi, China.
- 3 Departments of Surgery of Bone and Soft Tissue Tumor, Affili- ated Tumor Hospital of Guangxi Medical University, Nanning, Guangxi, China..
- 4 Departments of General Practice, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
- 5 Departments of Orthopedics, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China.
- 6 Department of Spine and Osteopathic Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, China..
- Sarcoma of the long bones.
- Pretreatment neutrophil-to lymphocyte ratio is correlated with response to neoadjuvant chemo- therapy as an independent prognostic indicator in breast cancer patients: a retrospective study.
- The role of the systemic inflammatory response in predicting outcomes in patients with advanced inoperable cancer: systematic review and meta-analysis.
- Predic- tive value of neutrophil/lymphocyte ratio for efficacy of preopera- tive chemotherapy in triple-negative breast cancer.
- Neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios can predict treatment response to neoadjuvant therapy in esophageal cancer.
- Prognos- tic value of the C-reactive protein to albumin ratio: a novel inflamma- tion-based prognostic indicator in osteosarcoma.
- Prognostic value of inflammation-based scores in patients with osteosarcoma.
- Baseline neutrophil–Lym- phocyte ratio and plate- let–lymphocyte ratio in rectal cancer patients following neoadjuvant chemoradiotherapy.
- Neutrophil-lymphocyte ratio predicts pathologic tumor response and survival after preoperative chemoradiation for rectal cancer.
- A derived neutrophil to lympho- cyte ratio predicts survival in patients with cancer.
- Baseline neutrophil- lympho- cyte ratio (≥2.8) as a prognostic factor for patients with locally advanced rectal cancer undergoing neoadjuvant chemoradiation.
- Neutrophil-lymphocyte ratio predicts response to chemotherapy in triple-negative breast cancer..
- The prognostic values of tumor-infiltrating neutrophils, lymphocytes and neutrophil/lymphocyte rates in bladder urothelial cancer.
- Intracellular signals and events activated by cytokines of the tumor necrosis factor super- family: from simple paradigms to complex mechanisms.
- Modulation of neutrophil granulocytes in the tumor microenvironment: mechanisms and consequences for tumor progression

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