XIAOHANG QIN1,2, CONG WANG3, and YONG YIN2
1Department of Graduate, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Ji’ nan, China, 2Department of Radiation Physics, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Ji’ nan, China, 3Department of Fourth Ward of Gynecological Tumor, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Shandong Ji’ nan, China
Synopsis
Bone marrow is a heterogeneous mixed tissue, which can be divided into red bone marrow with hematopoietic activity and yellow bone marrow with high fat content. Concurrent chemoradiotherapy can induce red bone marrow transfer into yellow bone marrow, increasing the bone marrow fat content and inhibiting hematopoietic function. The study used the MRI IDEAL IQ sequence to quantify the changes of pelvic bone marrow fat content receiving different doses of concurrent chemoradiotherapy for cervical cancer, and to determine associations with peripheral blood cell counts.
Introduction
Concurrent radiotherapy and chemotherapy can improve the overall survival rate and local control rate of patients with cervical cancer, but the incidence of ≥3 hematological toxicity (HT) is as high as 87%. Severe bone marrow suppression can delay or interrupt the process of radiotherapy and chemotherapy1,2. The active bone marrow of the pelvic and lumbar spine is located in the range of cervical cancer radiotherapy. Studies have shown that the dose limitation of active bone marrow as an organ at risk (OAR) can effectively reduce the incidence of blood toxicity3,4.
The IDEAL IQ sequence (iterative decomposition of water and fat with echo asymmetry and least squares estimation, IDEAL-IQ) of MRI (magnetic resonance imaging, MRI) is a fat quantitative 3D scanning technology that can achieve the purpose of separating water and fat and assess bone marrow fat content accurately. In present study the MRI IDEAL IQ sequence had been used to quantitatively the changes in bone marrow fat content of patients with cervical cancer during concurrent chemoradiotherapy and investigate associations between peripheral blood cell counts and fat content changes, to provide a basis for individualized bone marrow protection.Methods
54 patients with cervical cancer received concurrent chemoradiotherapy were retrospectively collected. Patients undergone T1WI, T2WI and IDEAL IQ serial scans (detailed information of MRI sequences was listed in Table 1) at baseline, RT mid-point, RT end and 1 month on a 3.0T MRI scanner (Discovery MR750w, GE Healthcare, Waukesha, WI). According to the actual radiation dose of each patient，the dose gradients of 5-10Gy, 10-15Gy, 15-20Gy, 20-30Gy, 30-40Gy, 40-50Gy, >50Gy were obtained respectively. IDEAL IQ FatFrac images were rigidly registered with dose maps to obtain the FatFrac images with dose distribution. GE workstation (AW4.7, GE Healthcare, Waukesha, WI) was used to analyze IDEAL IQ FatFrac images. A region of interest (ROI) was placed in the iliac bone (excluding cortical edges or blood vessels) under different dose gradients, and the values of bone marrow proton density fat fraction (PDFF%) in each ROI were counted. Absolute counts of white blood cells (WBC), neutrophils (ANC), lymphocytes (ALC), platelets (PLT) and hemoglobin (HGB) were prospectively collected over the course of treatment. Calculate the change rate of PDFF% value at RT-end (PDFF%post) compared with PDFF% value at baseline (PDFF%pre). Spearman rank correlations were performed by the nadir of peripheral blood cell counts versus bone marrow dose volume parameters and the changes in PDFF% at different dose gradients. All statistical tests had statistical significance defined as P<.05. Data analysis was performed in IBM SPSS Version25 (IBM SPSS Inc, Chicago, IL).Results
The counts of white blood cells (WBC), neutrophils (ANC), lymphocytes (ALC), platelets (PLT) and hemoglobin (HGB) were decreased during treatment (52.4%, 65.1%, 27.6%, 69.3% and 90% respect to baseline respectively). The ALC nadirs appeared at the midpoint of radiotherapy, and the WBC, ANC, PLT nadirs appeared at the end of radiotherapy. WBC, ANC, ALC and PLT increased at 1 month after radiotherapy. PDFF% demonstrated a significant dose-response relationship at all time point. At RT mid-point and RT end, PDFF% increased by 46.8% and 58.5% respectively. PDFF% decreased at RT end, but it still increased by 46.2% compared with the baseline at 1 month after radiotherapy. A significant positive correlation was observed between PDFF% and ANC nadirs at 5-10Gy (r = 0.62, P = 0.006). Similarly, correlations were observed between PDFF (%) and ALC nadirs at 5-10Gy (r = 0.554, P = 0.017).Discussion
The results of this study show that MRI IDEAL IQ FatFrac imaging can be used to quantify the changes in bone marrow composition during chemoradiotherapy. We confirmed the correlation between PDFF% and peripheral blood cell reduction, PDFF% changes and dose accumulation demonstrated a significant dose-response relationship. IDEAL IQ can distinguish red from yellow bone marrow by measuring bone marrow signal values. The combination of MRI and fat quantitative technology could accurately locate the position and range of active bone marrow, thereby providing a visual basis for individualized protection of bone marrow.Conclusion
MRI IDEAL IQ fat fraction imaging can noninvasive evaluate and track the changes of pelvic bone marrow fat content with concurrent chemoradiotherapy for cervical cancer. There is a strong correlation between low-dose radiation and hematological toxicity, which provide a basis for individualized protection of pelvic bone marrow during concurrent chemotherapy for cervical cancer.Acknowledgements
No acknowledgement found.References
1. Abu-Rustum NR, Yashar CM, Bean S, et al. NCCN Guidelines Insights: Cervical Cancer, Version 1.2020. J Natl Compr Canc Netw. 2020; 18(6):660-666.
2. Dueñas-González A, Zarbá JJ, Patel F, et al. Phase III, open-label, randomized study comparing concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin versus concurrent cisplatin and radiation in patients with stage IIB to IVA carcinoma of the cervix. J Clin Oncol. 2011; 29(13):1678-1685.
3. Huang J, Gu F, Ji T, et al. Pelvic bone marrow sparing intensity modulated radiotherapy reduces the incidence of the hematologic toxicity of patients with cervical cancer receiving concurrent chemoradiotherapy: a single-center prospective randomized controlled trial. Radiat Oncol. 2020; 15(1):180.
4. Kunos CA, Andrews SJ, Moore KN, et al. Randomized Phase II Trial of Triapine-Cisplatin-Radiotherapy for Locally Advanced Stage Uterine Cervix or Vaginal Cancers. Front Oncol. 2019; 9:1067.