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Bu F, Cao S, Deng X, Zhang Z, Feng X. Evaluation of C-reactive protein and fibrinogen in comparison to CEA and CA72-4 as diagnostic biomarkers for colorectal cancer. Heliyon 2023; 9:e16092. [PMID: 37215813 PMCID: PMC10196578 DOI: 10.1016/j.heliyon.2023.e16092] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2022] [Revised: 05/04/2023] [Accepted: 05/04/2023] [Indexed: 05/24/2023] Open
Abstract
Carcinoembryonic antigen (CEA) and carbohydrate antigen 72-4 (CA72-4) are commonly used markers for colorectal cancer (CRC) in clinical applications. However, low positivity rate and sensitivity limits their clinical effectiveness. In this study, we explored the potential of C-reactive protein (CRP) and fibrinogen to improve the diagnostic efficiency of traditional biomarkers of CRC. The concentrations of CRP and fibrinogen in plasma were significantly higher in CRC patients compared with benign or healthy controls. The area under the ROC curves (AUCs) showed that the diagnostic efficacy of CRP and fibrinogen was 0.745 (95% CI: 0.712-0.779) and 0.699 (95% CI: 0.663-0.734), respectively. AUC increased to 0.750 (95% CI: 0.716-0.784) when CRP and fibrinogen were combined. It also further improved to 0.889 (95% CI: 0.866-0.913) when CRP and fibrinogen were integrated with CEA and CA72-4. Moreover, this combination increased the maximum area under AUC to 0.857 (95% CI: 0.830-0.883), which effective differentiated CRC from benign disease. Overall, this study found that CRP and fibrinogen were highly expressed in the plasma of CRC patients, suggesting their potential to improve the diagnostic efficiency of traditional biomarkers of CRC.
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Affiliation(s)
- Fan Bu
- Department of Clinical Laboratory, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, China
| | - Shenyun Cao
- Department of Clinical Laboratory, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, China
| | - Xiangzhu Deng
- Department of Clinical Laboratory, Qingdao Youfu Hospital, Qingdao, 266075, China
| | - Zhijun Zhang
- Department of Clinical Laboratory, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, China
| | - Xiaodong Feng
- Department of Clinical Laboratory, Central Hospital Affiliated to Shandong First Medical University, Jinan, 250013, China
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2
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Gjyshi O, Grippin A, Andring L, Jhingran A, Lin LL, Bronk J, Eifel PJ, Joyner MM, Sastry JK, Yoshida-Court K, Solley TN, Napravnik TC, O'Hara MP, Hegde VL, Colbert LE, Klopp AH. Circulating neutrophils and tumor-associated myeloid cells function as a powerful biomarker for response to chemoradiation in locally advanced cervical cancer. Clin Transl Radiat Oncol 2023; 39:100578. [PMID: 36935860 PMCID: PMC10014332 DOI: 10.1016/j.ctro.2023.100578] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2022] [Revised: 01/06/2023] [Accepted: 01/08/2023] [Indexed: 01/12/2023] Open
Abstract
Purpose The immune system's role in mediating the cytotoxic effects of chemoradiotherapy remains not completely understood. The integration of immunotherapies into treatment will require insight into features and timing of the immune microenvironment associated with treatment response. Here, we investigated the role of circulating neutrophils and tumor-associated myeloid cells (TSAMs) as potential agents and biomarkers for disease-related outcomes in locally advanced cervical cancer (LACC). Material and Methods Hematologic parameters for two LACC patient cohorts, a retrospective clinical and a prospective translational cohort, were obtained at baseline, weekly during chemoradiotherapy for the retrospective cohort, biweekly during chemoradiotherapy for the prospective cohort, and at the first follow-up visit for both cohorts (mean 14.7 weeks, range 8.1-25.1 weeks for the prospective cohort and 5.3 weeks with a range of 2.7-9.0 weeks for the retrospective cohort). In both cohorts, baseline as well as mean and lowest on-treatment values for platelets, hemoglobin, absolute neutrophil count (ANC), and absolute lymphocyte count (ALC) were analyzed for correlations with disease-related outcomes. In the prospective cohort, circulating myeloid cells were isolated from peripheral blood mononuclear cells (PBMCs), and TSAMs were isolated from tumor tissue via a novel serial cytobrush sampling assay. The samples were analyzed by flow cytometry. Results In both cohorts, the only hematologic parameter significantly associated with survival was elevated on-treatment mean ANC (mANC), which was associated with lower local failure-free and overall survival rates in the retrospective and prospective cohorts, respectively. mANC was not associated with a difference in distant metastases. CD11b+CD11c- TSAMs, which act as a surrogate marker for intratumoral neutrophils, steadily decreased during the course of chemoRT and nadier'd at week 5 of treatment. Conversely, circulating myeloid cells identified from PBMCs steadily increased through week 5 of treatment. Regression analysis confirmed an inverse relationship between circulating myeloid cells and TSAMs at this time point. Conclusions These findings identify on-treatment mean neutrophil count as a predictor of disease-related outcomes, suggest that neutrophils contribute to chemoradiation treatment resistance, and demonstrate the importance of techniques to measure intratumoral immune activity.
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Affiliation(s)
- Olsi Gjyshi
- Department of Radiation Oncology, Saint Elizabeth Cancer Center, Edgewood, KY, United States
| | - Adam Grippin
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United States
| | - Lauren Andring
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United States
| | - Anuja Jhingran
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United States
| | - Lilie L. Lin
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United States
| | - Julianna Bronk
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United States
| | - Patricia J. Eifel
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United States
| | - Melissa M. Joyner
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United States
| | - Jagannadha K. Sastry
- Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Kyoko Yoshida-Court
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United States
| | - Travis N. Solley
- Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Tatiana Cisneros Napravnik
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United States
| | - Madison P. O'Hara
- Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Venkatesh L Hegde
- Department of Thoracic Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
| | - Lauren E. Colbert
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United States
- Corresponding authors at: Department of Radiation Oncology, Unit 1052, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd., Houston, TX, 77030, United States, (L.E. Colbert); Department of Radiation Oncology, Unit 1422, The University of Texas MD Anderson Cancer Center, 1400 Pressler St., Houston, TX, 7703, United States, (A.H. Klopp).
| | - Ann H Klopp
- Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas Department of Medicine, United States
- Corresponding authors at: Department of Radiation Oncology, Unit 1052, The University of Texas MD Anderson Cancer Center, 6565 MD Anderson Blvd., Houston, TX, 77030, United States, (L.E. Colbert); Department of Radiation Oncology, Unit 1422, The University of Texas MD Anderson Cancer Center, 1400 Pressler St., Houston, TX, 7703, United States, (A.H. Klopp).
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The Significance of Serum C-Reactive Protein and Neutrophil-Lymphocyte Ratio in Predicting the Diagnostic Outcomes of Renal Mass Biopsy Procedure. J Kidney Cancer VHL 2023; 10:9-14. [PMID: 36793395 PMCID: PMC9902900 DOI: 10.15586/jkcvhl.v10i1.259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 01/20/2023] [Indexed: 02/09/2023] Open
Abstract
This study aimed to investigate the predictive role of serum C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio (NLR) on renal mass biopsy outcomes. A total of 71 patients with suspected kidney masses who underwent renal mass biopsy procedure between January 2017 and January 2021 were retrospectively evaluated. Pathological results after the procedure were obtained and pre-procedural serum CRP and NLR levels were extracted from the patients' data. The patients were grouped into benign and malignant pathology groups according to the histopathology results. The parameters were compared between the groups. Diagnostic role of the parameters in terms of sensitivity, specificity, and positive and negative predictive values was also determined. Additionally, Pearson correlation analysis, and univariate and multivariate cox proportional hazard regression analyses were also performed to investigate the above association with tumor diameter and pathology results, respectively. At the end of the analyses, a total of 60 patients had malignant pathology on histopathological investigations of the mass biopsy specimens, whereas the remaining 11 patients had a benign pathological diagnosis. Significantly higher CRP and NLR levels were detected in the malignant pathology group. The parameters positively correlated with the malignant mass diameter, as well. Serum CRP and NLR determined the malignant masses before the biopsy with sensitivity and specificity of 76.6 and 81.8%, and 88.3 and 45.4%, respectively. Moreover, univariate and multivariate analyses showed that serum CRP level had a significant predictive value for malignant pathology (HR: 0.998, 95% CI: 0.940-0.967, P < 0.001 and HR: 0.951, 95% CI: 0.936-0.966, P < 0.001, respectively). In conclusion, serum CRP and NLR levels were significantly different in patients with malignant pathology after renal mass biopsy compared to the patients with benign pathology. Serum CRP level, in particular, diagnosed malignant pathologies with acceptable sensitivity and specificity values. Additionally, it had a substantial predictive role in determining the malign masses prior the biopsy. Therefore, pre-biopsy serum CRP and NLR levels may be used to predict the diagnostic outcomes of renal mass biopsy in clinical practice. Further studies with larger cohorts can prove our findings in the future.
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Sung PS, Lee IK, Roh PR, Kang MW, Ahn J, Yoon SK. Blood-based biomarkers for immune-based therapy in advanced HCC: Promising but a long way to go. Front Oncol 2022; 12:1028728. [PMID: 36387149 PMCID: PMC9659956 DOI: 10.3389/fonc.2022.1028728] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 10/17/2022] [Indexed: 09/08/2024] Open
Abstract
The introduction of immune checkpoint inhibitors (ICIs) represents a key shift in the management strategy for patients with hepatocellular carcinoma (HCC). However, there is a paucity of predictive biomarkers that facilitate the identification of patients that would respond to ICI therapy. Although several researchers have attempted to resolve the issue, the data is insufficient to alter daily clinical practice. The use of minimally invasive procedures to obtain patient-derived specimen, such as using blood-based samples, is increasingly preferred. Circulating tumor DNA (ctDNA) can be isolated from the blood of cancer patients, and liquid biopsies can provide sufficient material to enable ongoing monitoring of HCC. This is particularly significant for patients for whom surgery is not indicated, including those with advanced HCC. In this review, we summarize the current state of understanding of blood-based biomarkers for ICI-based therapy in advanced HCC, which is promising despite there is still a long way to go.
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Affiliation(s)
- Pil Soo Sung
- Department of Biomedicine and Health Sciences, The Catholic University Liver Research Center, College of Medicine, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, South Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea
| | - Isaac Kise Lee
- Department of Computer Science and Engineering, Incheon National University, Incheon, South Korea
| | - Pu Reun Roh
- Department of Biomedicine and Health Sciences, The Catholic University Liver Research Center, College of Medicine, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, South Korea
| | - Min Woo Kang
- Department of Biomedicine and Health Sciences, The Catholic University Liver Research Center, College of Medicine, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, South Korea
| | - Jaegyoon Ahn
- Department of Computer Science and Engineering, Incheon National University, Incheon, South Korea
| | - Seung Kew Yoon
- Department of Biomedicine and Health Sciences, The Catholic University Liver Research Center, College of Medicine, POSTECH-Catholic Biomedical Engineering Institute, The Catholic University of Korea, Seoul, South Korea
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, South Korea
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Bannaga A, Arasaradnam RP. Neutrophil to lymphocyte ratio and albumin bilirubin grade in hepatocellular carcinoma: A systematic review. World J Gastroenterol 2020; 26:5022-5049. [PMID: 32952347 PMCID: PMC7476180 DOI: 10.3748/wjg.v26.i33.5022] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Revised: 08/10/2020] [Accepted: 08/25/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is a frequent cause of cancer related death globally. Neutrophil to lymphocyte ratio (NLR) and albumin bilirubin (ALBI) grade are emerging prognostic indicators in HCC.
AIM To study published literature of NLR and ALBI over the last five years, and to validate NLR and ALBI locally in our centre as indicators of HCC survival.
METHODS A systematic review of the published literature on PubMed of NLR and ALBI in HCC over the last five years. The search followed the guidelines of the preferred reporting items for systematic reviews and meta-analyses. Additionally, we also investigated HCC cases between December 2013 and December 2018 in our centre.
RESULTS There were 54 studies describing the relation between HCC and NLR and 95 studies describing the relation between HCC and ALBI grade over the last five years. Our local cohort of patients showed NLR to have a significant negative relationship to survival (P = 0.011). There was also significant inverse relationship between the size of the largest HCC nodule and survival (P = 0.009). Median survival with alpha fetoprotein (AFP) < 10 KU/L was 20 mo and with AFP > 10 KU/L was 5 mo. We found that AFP was inversely related to survival, this relationship was not statically significant (P = 0.132). Mean survival for ALBI grade 1 was 37.7 mo, ALBI grade 2 was 13.4 months and ALBI grade 3 was 4.5 mo. ALBI grades performed better than Child Turcotte Pugh score in detecting death from HCC.
CONCLUSION NLR and ALBI grade in HCC predict survival better than the conventional alpha fetoprotein. ALBI grade performs better than Child Turcotte Pugh score. These markers are done as part of routine clinical care and in cases of normal alpha fetoprotein, these markers could give a better understanding of the patient disease progression. NLR and ALBI grade could have a role in modified easier to learn staging and prognostic systems for HCC.
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Affiliation(s)
- Ayman Bannaga
- Department of Gastroenterology and Hepatology, University Hospital Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, West Midlands, United Kingdom
- Warwick Medical School, University of Warwick, Coventry CV4 7HL, West Midlands, United Kingdom
| | - Ramesh P Arasaradnam
- Department of Gastroenterology and Hepatology, University Hospital Coventry and Warwickshire NHS Trust, Coventry CV2 2DX, West Midlands, United Kingdom
- Warwick Medical School, University of Warwick, Coventry CV4 7HL, West Midlands, United Kingdom
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Zhuang Y, Yuan BY, Hu Y, Chen GW, Zhang L, Zhao XM, Chen YX, Zeng ZC. Pre/Post-Treatment Dynamic of Inflammatory Markers Has Prognostic Value in Patients with Small Hepatocellular Carcinoma Managed by Stereotactic Body Radiation Therapy. Cancer Manag Res 2019; 11:10929-10937. [PMID: 32099457 PMCID: PMC6997220 DOI: 10.2147/cmar.s231901] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2019] [Accepted: 12/19/2019] [Indexed: 12/26/2022] Open
Abstract
Purpose The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are inflammatory indexes that may reflect immune response to tumors and prognosis. We investigated the prognostic values of pre-treatment and post-treatment NLR and PLR and changes in those ratios in patients with small hepatocellular carcinoma (sHCC) treated with stereotactic body radiation therapy (SBRT). Patients and methods Sixty patients who received SBRT were retrospectively reviewed. NLR and PLR were calculated by division of neutrophil and platelet counts, respectively, by lymphocyte counts. Independent factors for progression-free survival (PFS) and overall survival (OS) were determined by the Kaplan–Meier method, log-rank test, and Cox multivariate regression. Hazard ratios (HRs) and 95% confidence intervals (CIs) were also calculated. Results The median follow-up was 36.9 (range: 4.1–73.5) months. Median PFS was 21.4 (range: 1.8–66.9) months. The 1-year and 2-year PFS rates were 76.7% and 55.0%, respectively. The 1-year and 2-year OS rates were 95.0% and 78.3%, respectively. In multivariate analysis, post-treatment PLR ≥263.0 indicated both poor PFS (HR: 3.70; 95% CI: 1.07–12.76, p=0.038) and OS (HR: 3.23; 95% CI: 1.01–9.11, p=0.043) for sHCC patients treated with SBRT. In addition, the presence of hepatitis infection and a low level of red blood cell count were also proved to be significantly associated with patients’ poor prognosis (p<0.05 for each). Post-treatment increase in NLR ≥2.7-fold was shown to be a negative independent predictor of inferior OS (HR: 3.43; 95% CI: 1.14–10.38, p=0.029). Conclusion High post-treatment PLR and change in NLR ≥2.7-fold were associated with poor prognosis in patients treated with SBRT and might be considered as reliable and independent prognostic biomarkers for patients with sHCC.
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Affiliation(s)
- Yuan Zhuang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Bao-Ying Yuan
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Yong Hu
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Gen-Wen Chen
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Li Zhang
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Xiao-Mei Zhao
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Yi-Xing Chen
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
| | - Zhao-Chong Zeng
- Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China
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Park EY, Kim YS, Choi KH, Song JH, Lee HC, Hong SH, Kang JH. Prognostic value of neutrophil-to-lymphocyte ratio in locally advanced non-small cell lung cancer treated with concurrent chemoradiotherapy. Radiat Oncol J 2019; 37:166-175. [PMID: 31591864 PMCID: PMC6790800 DOI: 10.3857/roj.2019.00220] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/22/2019] [Accepted: 07/08/2019] [Indexed: 12/13/2022] Open
Abstract
Purpose This study aimed to investigate neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in patients with locally advanced non-small cell lung cancer (NSCLC) who received concurrent chemoradiotherapy (CCRT). Materials and Methods We retrospectively analyzed 66 patients with locally advanced NSCLC treated with definitive CCRT. Among these patients, 95% received paclitaxel/carboplatin or docetaxel/cisplatin. The median radiation dose was 66 Gy in 33 fractions. The NLR and PLR before/after CCRT were evaluated. The maximally selected log-rank test was used to obtain the cutoff values related to the overall survival (OS). Results Patients with high post-CCRT NLR (>3.12) showed worse OS, locoregional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS) than those with low NLR (2-year OS: 25.8% vs. 68.2%, p < 0.001; 2-year LRPFS: 12.9% vs. 33.8%, p = 0.010; 2-year DMFS: 22.6% vs. 38.2%, p = 0.030). Patients with high post-CCRT PLR (>141) showed worse OS and LRPFS than those with low PLR (2-year OS: 37.5% vs. 71.1%, p = 0.004; 2-year LRPFS: 16.5% vs. 40.3%, p = 0.040). Patients with high NLR change (>1.61) showed worse OS and LRPFS than those with low NLR change (2-year OS: 26.0% vs. 59.0%, p < 0.001; 2-year LRPFS: 6.8% vs. 31.8%, p = 0.004). The planning target volume (hazard ration [HR] = 2.05, p = 0.028) and NLR change (HR = 3.17, p = 0.025) were the significant factors for OS in the multivariate analysis. Conclusion NLR change after CCRT was associated with poor prognosis of survival in patients with locally advanced NSCLC. An elevated NLR after CCRT might be an indicator of an increased treatment failure risk.
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Affiliation(s)
- Eun Young Park
- Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Yeon-Sil Kim
- Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Kyu Hye Choi
- Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jin Ho Song
- Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Hyo Chun Lee
- Department of Radiation Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Sook-Hee Hong
- Department of Medical Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
| | - Jin-Hyoung Kang
- Department of Medical Oncology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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Abstract
Nearly two-thirds of cancer patients are treated with radiation therapy (RT), often with the intent to achieve complete and permanent tumor regression (local control). RT is the primary treatment modality used to achieve local control for many malignancies, including locally advanced cervical cancer, head and neck cancer, and lung cancer. The addition of concurrent platinum-based radiosensitizing chemotherapy improves local control and patient survival. Enhanced outcomes with concurrent chemoradiotherapy may result from increased direct killing of tumor cells and effects on nontumor cell populations. Many patients treated with concurrent chemoradiotherapy exhibit a decline in neutrophil count, but the effects of neutrophils on radiation therapy are controversial. To investigate the clinical significance of neutrophils in the response to RT, we examined patient outcomes and circulating neutrophil counts in cervical cancer patients treated with definitive chemoradiation. Although pretreatment neutrophil count did not correlate with outcome, lower absolute neutrophil count after starting concurrent chemoradiotherapy was associated with higher rates of local control, metastasis-free survival, and overall survival. To define the role of neutrophils in tumor response to RT, we used genetic and pharmacological approaches to deplete neutrophils in an autochthonous mouse model of soft tissue sarcoma. Neutrophil depletion prior to image-guided focal irradiation improved tumor response to RT. Our results indicate that neutrophils promote resistance to radiation therapy. The efficacy of chemoradiotherapy may depend on the impact of treatment on peripheral neutrophil count, which has the potential to serve as an inexpensive and widely available biomarker.
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9
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Wu XL, Li ZY, Bi XY, Zhao H, Zhao JJ, Zhou JG, Han Y, Huang Z, Zhang YF, Cai JQ. Human leukocyte antigen gene polymorphisms are associated with systemic inflammation in hepatitis B virus-related hepatocellular carcinoma. Cancer Manag Res 2018; 10:2315-2324. [PMID: 30104900 PMCID: PMC6074760 DOI: 10.2147/cmar.s167574] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Background Systemic inflammation (SI) is associated with tumor progression and overall survival (OS) in patients with hepatocellular carcinoma (HCC). The presence of some single nucleotide polymorphisms (SNPs) in the human leukocyte antigen (HLA) region can influence the prognosis of patients with hepatitis B virus (HBV)-related HCC, although the mechanism remains unknown. This study aimed to analyze the correlations between HLA gene polymorphisms and SI. Patients and methods This study included 330 patients with HCC. The clinical parameters were reviewed, and five SNPs, namely rs2647073, rs3997872, rs3077, rs7453920, and rs7768538, were genotyped using the MassARRAY system. Results The rs3997872, rs7453920, and rs7768538 genotypes were found to be significantly associated with OS (P<0.05). The rs7453920 genotype was significantly associated with the neutrophil/lymphocyte ratio (NLR; P=0.001), which was used as an SI index with a threshold determined by receiver operating characteristic analysis. An elevated NLR was also an independent predictor of OS according to univariate and multivariate analyses (P<0.001). Conclusion Our data show that HLA gene polymorphisms are associated with SI in patients with HBV-related HCC, and the absence of minor allele A (rs7453920) promotes SI and shortens OS.
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Affiliation(s)
| | - Zhi-Yu Li
- Department of Hepatobiliary Surgery,
| | - Xin-Yu Bi
- Department of Hepatobiliary Surgery,
| | - Hong Zhao
- Department of Hepatobiliary Surgery,
| | | | | | - Yue Han
- Department of Interventional Therapies, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China
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10
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Nesseler JP, Schaue D, McBride WH, Nickers P. [Inflammatory and immune biomarkers of radiation response]. Cancer Radiother 2018; 22:180-192. [PMID: 29650389 DOI: 10.1016/j.canrad.2017.09.007] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2017] [Accepted: 09/08/2017] [Indexed: 02/07/2023]
Abstract
In radiotherapy, the treatment is adapted to each individual to protect healthy tissues but delivers most of time a standard dose according to the tumor histology and site. The only biomarkers studied to individualize the treatment are the HPV status with radiation dose de-escalation strategies, and tumor hypoxia with dose escalation to hypoxic subvolumes using FMISO- or FAZA-PET imaging. In the last decades, evidence has grown about the contribution of the immune system to radiation tumor response. Many preclinical studies have identified some of the mechanisms involved. In this context, we have realised a systematic review to highlight potential inflammatory and immune biomarkers of radiotherapy response. Some are inside the tumor microenvironment, as lymphocyte infiltration or PD-L1 expression, others are circulating biomarkers, including different types of hematological cells, cytokines and chemokines.
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Affiliation(s)
- J P Nesseler
- Department of radiation oncology, David Geffen school of medicine, university of California at Los Angeles, 10833 Le Conte avenue, 90095-1714 Los Angeles, CA, États-Unis.
| | - D Schaue
- Department of radiation oncology, David Geffen school of medicine, university of California at Los Angeles, 10833 Le Conte avenue, 90095-1714 Los Angeles, CA, États-Unis
| | - W H McBride
- Department of radiation oncology, David Geffen school of medicine, university of California at Los Angeles, 10833 Le Conte avenue, 90095-1714 Los Angeles, CA, États-Unis
| | - P Nickers
- Départment de radiothérapie, centre François-Baclesse, rue Émile-Mayrisch, 4240 Esch-sur-Alzette, Luxembourg
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Basler L, Andratschke N, Ehrbar S, Guckenberger M, Tanadini-Lang S. Modelling the immunosuppressive effect of liver SBRT by simulating the dose to circulating lymphocytes: an in-silico planning study. Radiat Oncol 2018; 13:10. [PMID: 29357886 PMCID: PMC5778751 DOI: 10.1186/s13014-018-0952-y] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2017] [Accepted: 01/03/2018] [Indexed: 12/18/2022] Open
Abstract
Background Tumor immune-evasion and associated failure of immunotherapy can potentially be overcome by radiotherapy, which however also has detrimental effects on tumor-infiltrating and circulating lymphocytes (CL). We therefore established a model to simulate the radiation-dose delivered to CL. Methods A MATLAB-model was established to quantify the CL-dose during SBRT of liver metastases by considering the factors: hepatic blood-flow, −velocity and transition-time of individual hepatic segments, as well as probability-based recirculation. The effects of intra-hepatic tumor-location and size, fractionation and treatment planning parameters (VMAT, 3DCRT, photon-energy, dose-rate and beam-on-time) were analyzed. A threshold dose ≥0.5Gy was considered inactivating CL and CL0.5 (%) is the proportion of inactivated CL. Results Mean liver dose was mostly influenced by treatment-modality, whereas CL0.5 was mostly influenced by beam-on-time. 3DCRT and VMAT (10MV-FFF) resulted in lowest CL0.5 values of 16 and 19%. Metastasis location influenced CL0.5, with a mean of 19% for both apical and basal and 31% for the central location. PTV-volume significantly increased CL0.5 from 27 to 67% (10MV-FFF) and from 31 to 98% (6MV-FFF) for PTV-volumes ranging from 14cm3 to 268cm3. Conclusion A simulation-model was established, quantifying the strong effects of treatment-technique, tumor-location and tumor-volume on dose to CL with potential implications for immune-optimized treatment-planning in the future. Electronic supplementary material The online version of this article (doi: 10.1186/s13014-018-0952-y) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- L Basler
- University Hospital Zurich, Department of Radiation Oncology, University of Zurich, Rämistrasse 100, CH 8091, Zürich, Switzerland.
| | - N Andratschke
- University Hospital Zurich, Department of Radiation Oncology, University of Zurich, Rämistrasse 100, CH 8091, Zürich, Switzerland
| | - S Ehrbar
- University Hospital Zurich, Department of Radiation Oncology, University of Zurich, Rämistrasse 100, CH 8091, Zürich, Switzerland
| | - M Guckenberger
- University Hospital Zurich, Department of Radiation Oncology, University of Zurich, Rämistrasse 100, CH 8091, Zürich, Switzerland
| | - S Tanadini-Lang
- University Hospital Zurich, Department of Radiation Oncology, University of Zurich, Rämistrasse 100, CH 8091, Zürich, Switzerland
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Bae SH, Jang WI, Park HC. Intensity-modulated radiotherapy for hepatocellular carcinoma: dosimetric and clinical results. Oncotarget 2017; 8:59965-59976. [PMID: 28938697 PMCID: PMC5601793 DOI: 10.18632/oncotarget.19219] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 06/02/2017] [Indexed: 12/15/2022] Open
Abstract
Since the introduction of 3-dimensional conformal radiotherapy (3DCRT), new radiotherapy techniques have expanded the indication of radiotherapy for the treatment of hepatocellular carcinoma (HCC), from the hitherto palliative to a now curative-intent purpose. Intensity-modulated radiotherapy (IMRT), currently the most advanced radiotherapy technique, is considered an attractive option for the treatment of HCC, and is more widely applied because it can deliver a higher dose to the tumor than 3DCRT while sparing surrounding normal organs. However, the advantages and potential disadvantages of IMRT for treating HCC have not been fully established. This article deals with three different IMRT techniques, including static IMRT and volumetric modulated arc therapy using conventional multileaf collimator (MLC) mounted linear accelerators, and helical IMRT using binary MLC mounted helical tomotherapy machine. We review dosimetric and clinical studies for these IMRT techniques for the treatment of HCC.
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Affiliation(s)
- Sun Hyun Bae
- Department of Radiation Oncology, Soonchunhyang University College of Medicine, Bucheon, Korea
| | - Won Il Jang
- Department of Radiation Oncology, Korea Institute of Radiological and Medical Sciences, Seoul, Korea
| | - Hee Chul Park
- Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Medical Device Management and Research, SAIHST, Sungkyunkwan University, Seoul, Korea
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