Dr Rohit Bhardwaj obtained MBBS (2008–2013) from Maulana Azad Medical College, New Delhi, obtained MD in Radiodiagnosis (2016–2019) from Assam Medical College, Dibrugarh, Assam, and is presently working as a Consultant Radiologist in Nector Diagnostics, Sector 24, Rohini, New Delhi, 110085.
Purpose To evaluate the added-value of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the preoperative assessment of carcinoma cervix.
Methods This prospective study was carried out on histopathologically proven 45 patients of carcinoma cervix presented to a tertiary care hospital with bleeding per vagina between August 2017 and July 2018. Relevant local per vaginal examination and MRI examination of the pelvis were performed.
Results A total of 45 patients with carcinoma of the cervix, having 11 patients (24.4%) in Stage-I, 22 patients (48.9%) in Stage-II, 3 patients (6.7%) in Stage-III and 9 patients (20%) in stage-IV, were included in this study sample. The mean ADC value of the carcinoma of cervix was 0.802 ± 0.123 [SD] × 10– 3 mm2/ s. The stage-I carcinoma cervix had a mean ADC value of 0.915 ± 0.109 [SD] × 10– 3 mm2/ s, Stage-II 0.778 ± 0.099 [SD] × 10– 3 mm2/ s, Stage-III 0.762 ± 0.123 [SD] × 10– 3 mm2/ s and Stage-IV 0.737 ± 0.116 [SD] × 10– 3 mm2/ s. ROC curve analysis showed the percentage of signal intensity changes within cervical tumor on arterial phase of DCE-MRI had a threshold value of 42.25 in differentiating Stage-I carcinoma of cervix from other stages with a sensitivity of 81.8% and specificity of 44.1%.
Conclusion The DWI and DCE-MRI added valuable inputs over conventional MR sequences in the early diagnosis and preoperative staging of carcinoma cervix. DCE-MRI had a high accuracy for assessing the cervical stromal and parametrial invasions, which helps in selecting the optimal therapeutic protocol and prognostication in gynecological malignancies.
Keywords : Magnetic resonance imaging (MRI) · Cervical malignancy · Apparent diffusion coefficient (ADC)
Cervical cancer is one of the major public health problems in developing countries like India. In 2018, cervical cancer is the fourth-most common cause of cancer incidence and mortality in women worldwide [1]. An estimated value of 570,000 cases and 311,000 deaths resulted from cervical cancer in 2018 worldwide [1]. The estimated age-standardised cervical cancer incidence was 13.1 per 100,000 women worldwide and it varied among countries from less than 2 to 75 per 100,000 women [1].
Cervical cancer accounting for 17% of all cancer deaths among women aged between 30 and 69 years [2]. 5 years of survival rates of patients with carcinoma cervix with FIGO 2018 stage-IB1, IB2, IB3, IIA1, IIA2, IIIC1 and III C2 were 95.3%, 95.1%, 90.4%, 92.4% 86.4%, 81.9% and 56.3%, respectively [3]. India alone accounts for one-quarter of the worldwide burden of cervical cancers and it contributes to approximately 6–29% of all cancers in women in India [2, 4].
The accurate staging of carcinoma cervix is important for guiding treatment options and determining patient prognosis. MRI is superior to CT scan in staging of carcinoma of the cervix and it may aid in differentiating residual or recurrent tumor from radiation fibrosis [5]. In post-treated patient with carcinoma cervix, reappearance of T2WI hypointensities in the cervical stroma indicates complete response to radiotherapy or chemotherapy and which helps in follow-up assessment [5]. Cross-sectional imaging plays an important role in the revised 2018 International Federation of Gynecology and Obstetrics (FIGO) staging system for uterine cervical cancer [6].
MRI can determine the parametrial invasion on basis of loss of T2WI hypointense cervical stromal ring [5] with a negative predictive value of 94–100% [7]. Additional features of parametrial invasion are spiculated tumor-parametrium interface, enhancing soft tissue extension into parametrium or encasement of periuterine vessels [7].
MRI can determine the parametrial invasion on basis of loss of T2WI hypointense cervical stromal ring [5] with a negative predictive value of 94–100% [7]. Additional features of parametrial invasion are spiculated tumor-parametrium interface, enhancing soft tissue extension into parametrium or encasement of periuterine vessels [7].
Lymph nodes can be easily detected on DW images as ovoid structures of high signal intensity and which increases the diagnostic accuracy in differentiating malignant and benign lymph nodes based on ADC value [13]. Lymphadenopathy detected at cross-sectional imaging is a major prognostic factor for survival and an important determinant in treatment planning [14].
DCE-MRI indirectly evaluates the distribution of contrast by measuring the tissue enhancement over a period of time. The signal intensity (SI) values can be recorded before, during and after contrast administration for creating a dynamic time-signal intensity (TSI) curve generated by using a fixed region of interest (ROI) within the organ imaged [15]. This study aims to evaluate the added-value of diffusionweighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in the preoperative assessment of carcinoma cervix.
Materials and Methods
A prospective cross-sectional study was conducted at our institution on histopathologically proven 45 patients of carcinoma cervix presented with bleeding per vagina between August 2017 and July 2018. This study was approved by institutional ethics review committee.
MRI Protocols
The patients underwent an MRI scan of the Pelvis, using a 1.5 T MR scanner, Siemens Magnatom Avanto (Siemens Medical Systems, Erlangen, Germany). Conventional MRI protocol sequences of female pelvis were obtained with phased-array surface coil followed by DWI and DCE-MRI imaging. The various MRI findings were correlated with histopathological findings.
Various MRI Sequences Parameters
Sagittal T1WI images were obtained with TE: 10–12 ms, TR: 500–600 ms, slice thickness: 4 mm, flip angle: 150°, Matrix 256 × 256, FOV: 190–200.
Sagittal T2WI images were obtained with TE: 90–105 ms, TR: 4800–6000 ms, slice thickness: 4 mm, flip angle: 150°, Matrix 256 × 256, FOV: 190–200.
T2WI true coronal images were obtained with TE: 90–105 ms, TR: 5000 -6000 ms, slice thickness: 4 mm, flip angle: 150°, Matrix 256 × 256, FOV: 240–260.
Fat-suppressed axial T2WI images were obtained with TE: 90-100 ms, TR: 4500–5500 ms, slice thickness: 4 mm, Matrix 256 × 256, FOV: 200–240.
DWI images were obtained with TE: 80-90 ms, TR: 2800-3200 ms, slice thickness: 5 mm, Matrix 256 × 256, FOV: 200–240 with b values b = 1000 s/mm2.
Post-contrast sagittal T1-VIBE sequences were obtained with TE: 1.25 ms, TR: 3.2 ms, slice thickness: 1.4 mm, flip angle: 10°, Matrix 256 × 256, FOV: 220–320. After injecting I.V. Gadopentetate dimeglumine at a dose of 0.1 mmol/kg body weight and infusion rate of 3–4 ml/s followed by 20 ml normal saline flush obtained four Phases including pre-contrast, arterial, venous and equilibrium phases.
Of the 45 female patients of cervical cancer in our study sample, having a mean age of 51.7 ± 10.7 [SD] years, majority of 17 patients (37.8%) belonged to the 51–60 years age group followed by 10 patients (22.2%) in the 41–50 years age group. Thirty-seven (82.8%) patients presented with episodes of bleeding per vagina, foul smelled white discharge, 6 (13.3%) patients with bleeding per vagina and decreased urination and 2 (4.4%) patients with rectal and per vaginal bleeding. Stage-I carcinoma cervix observed in 11 patients (24.4%), Stage-II in 22 patients (48%) (Figs. 1, 2, 3), stage- III in 3 patients (6.7%) and stage-IV in 9 patients (20%) (Fig. 4) according to 2018 Revised FIGO staging. T2WI isointense signal in cervical tumor is observed in 26 patients (57.8%) (Fig. 4), T2WI hyperintensities in 13 patients (28.9%) (Fig. 1, 3) while T1WI isointensities in 27 patients (60%) and hypointensities in 18 patients (40%). Table 1 shows the mean ADC values of various stages of cervical carcinoma according to the 2018 Revised FIGO staging. The mean ADC value of the carcinoma of cervix was 0.802 ± 0.123 [SD] × 10– 3 mm2/ s. The stage-I carcinoma cervix had mean ADC value of 0.915 ± 0.109 [SD] × 10– 3 mm2/ s, Stage-II 0.778 ± 0.099 [SD] × 10– 3 mm2/ s, Stage-III 0.762 ± 0.123 [SD] × 10– 3 mm2/ s and Stage-IV 0.737 ± 0.116 [SD] × 10– 3 mm2/ s. There was a statistically significant correlation found between the mean ADC value of Stage-I carcinoma cervix with II, III and IV with p value < 0.05 Table 1.
the revised FIGO staging and histological grades are shown in Table 2. There was a statistical significance (p value of 0.035) for SI changes in cervical tumors in the arterial phase for differentiating Stage-I carcinoma of cervix from other stages on DCE-MRI Table 5. ROC curve analysis showed a percentage of SI change threshold of 42.25 in the arterial phase that can differentiate Stage-I carcinoma of cervix from other stages with a sensitivity of 81.8% and specificity of 44.1%. The highest relative tumor-to-myometrial enhancement indexes were observed on arterial phase in Stage-I and lowest indexes were found in Stage-III. There were no significant differences between well-differentiated and poorly differentiated cervical tumors in relative tumor-to-myometrial enhancement index in either phase (arterial, p value = 0.94; equilibrium, p value = 0.721) Table 3. Table 4 shows the comparison between the MRI and pathological staging of cervical cancer according to the revised 2018 FIGO staging.
Cervical cancer is a major cause of morbidity and mortality in developing countries. Institution of screening, prevention measures with early MRI detection and staging of cervical cancer helps to guide proper treatment, radiation treatment planning/monitoring and detection of post-treatment recurrence [16].
MRI plays an important role in accurate staging of cervical cancer to distinguish early disease (stage-I and IIA) that can be treated surgically or concurrent chemoradiotherapy from the advanced disease (stage-IIB or greater) that is usually treated with radiation therapy or concurrent chemoradiotherapy. The outcome following standard therapeutic approaches were governed by accurate MRI detection of tumor location, size, depth of stromal invasion, parametrial invasion, lower uterine segment affection, vaginal extension, pelvic sidewall invasion and associated lymph nodal involvement with advanced MRI imaging like DWI, DCE-MRI and MR spectroscopy [7, 12].
Several published studies evaluated the prognostic significance of ADC value in the diagnosis and management of the cervical cancer. Nakamura et al. [10] observed statistical significance of mean ADC value of cervical tumor with the FIGO stage, tumor size, stroma and parametrial infiltration, lymph node metastasis and lymphovascular space involvement in 80 surgically treated patients. T2WI able to detect early cervical tumors as hyperintense lesion with disruption of the T2W hypointense cervical stromal ring, speculated tumor invasion and encasement of periuterine vessels [17]. Various previous studies showed increasing ADC value in the post-treatment carcinoma cervix in patient response to the treatment [18–20]. Chen et al. [21] observed 100% sensitivity and 84.8% specificity of DWI for the detection of cervical cancer. In our study sample, the mean ADC value of the carcinoma of cervix was 0.802 ± 0.123 [SD] × 10– 3 mm2/ s, where stage-I carcinoma cervix had mean ADC value of 0.915 ± 0.109 [SD] × 10– 3 mm2/ s, Stage- II 0.778 ± 0.099 [SD] × 10– 3 mm2/ s, Stage-III 0.762 ± 0.123 [SD] × 10– 3 mm2/ s and Stage-IV 0.737 ± 0.116 [SD] × 10– 3 mm2/ s Table 1. In our study sample, ADC mapping had a sensitivity of 90.9% and specificity of 70.6% in detecting Stage-I, sensitivity of 68.2% and specificity 30.4% in Stage- II, sensitivity of 66.7% and specificity 38.1% in Stage-III and sensitivity of 66.7% and specificity of 22.2% in Stage-IV (Fig. 5]. Nakamura et al. [10] found mean ADC value of cervical cancer was 0.852 × 10– 3 mm2/ s which is correlated with our study sample.
Declarations
Conflict of interest The authors declare that they have no conflict of interest.
Ethical Standards We confirm that this manuscript has not been published elsewhere and it not under consideration by another journal.
Ethical Statement All investigations and procedures in the study were in accordance with the ethical standards of the institution.
Informed Consent Informed consent was obtained from all individual participants included in the study.
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