Prospective multimodal imaging assessment of locally advanced cervical cancer patients administered by chemoradiation followed by radical surgery-the "PRICE" study 2: role of conventional and DW-MRI.

OBJECTIVES: To assess the diagnostic performance of conventional and DW-MRI parameters in the detection of residual tumor in locally advanced cervical cancer (LACC) patients treated with neoadjuvant chemoradiotherapy (nCRT) and radical surgery METHODS: Between October 2010 and June 2014, 88 patients with histologically documented cervical cancer (FIGO stage IB2-IVA) were prospectively included in the study. Maximum tumor diameters (maxTD), tumor volume (TV), DWI signal intensity (SI), and ADCmean were evaluated at MRI after nCRT. Histology was the reference standard. Treatment response was classified as complete (CR) or partial (PR). Comparisons were made with Mann-Whitney, χ2, and Fisher's exact tests. ROC curves were generated for variables to evaluate diagnostic ability to predict PR and to determine the best cutoff value to predict PR. For each diagnostic test, sensitivity, specificity, and accuracy were calculated. RESULTS: TV and maxTD were significantly smaller in the CR than in the PR group (p < 0.001; p = 0.001) and showed, respectively, sensitivity of 68.8%, specificity of 72.5%, and accuracy of 70.5% and of 47.9, 87.5, and 65.9% in predicting PR. High DWI SI was more frequent in the PR (81.8%) than in the CR group (55.3%) (p < 0.009). ADCmean was higher in the CR (1.3 × 10-3 mm2/s, range 0.8-1.6 × 10-3 mm2/s) than in the PR group (1.1 × 10-3 mm2/s; range 0.7-1.8 × 10-3 mm2/s) (p < 0.018). High DWI SI showed sensitivity, specificity, and accuracy of 81.8, 44.7, and 64.6% in predicting PR. The ADCmean measurement increased sensitivity, specificity, and accuracy to 75.0, 76.2, and 75.4%. CONCLUSIONS: Conventional and DW-MRI is useful for predicting PR after nCRT in LACC. The ADCmean value ≤ 1.1 × 10-3 mm2/s was the best cutoff to predict PR. KEY POINTS: • Conventional and DW-MRI is useful for predicting PR after nCRT in LACC. • The combination of T2 sequences, DW-MRI, and the quantitative measurement of ADC mean showed the best results in predicting pathological PR. • The best cutoff for predicting pathological PR was ADCmeanvalue ≤ 1.1 × 10-3 mm2/s.

The PRICE study: The role of conventional and diffusion-weighted magnetic resonance imaging in assessment of locally advanced cervical cancer patients administered by chemoradiation followed by radical surgery.

OBJECTIVES: To analyse the role of DW-MRI in early prediction of pathologically-assessed residual disease in locally-advanced cervical cancer (LACC) treated with neoadjuvant chemoradiotherapy followed by radical surgery. METHODS: Between October 2010-June 2014, 108 women with histologically-proven cervical cancer were screened; 88 were included in this study. Tumour volume (TV) and ADCmean were measured before (baseline-MRI) and after 2 weeks of chemoradiotherapy (early-MRI). According to histopathology, treatment response was classified as complete (CR) or partial (PR). Comparisons were made with Mann-Whitney, Wilcoxon and χ2 tests. ROC curves were generated for statistically significant parameters on univariate analysis. RESULTS: CR and PR were documented in 40 and 48 patients. At baseline-MRI, TV did not differ between groups. At early-MRI, TV was higher in PR than in CR (p=0.001). ΔTV reduction after treatment was lower in PR than in CR (63.6% vs. 81.1%; p=0.001). At baseline-MRI and early-MRI, ADCmean did not differ between PR and CR. ROC curve showed best cut-off for predicting pathological PR was ΔTV reduction of 73% with sensitivity, specificity, accuracy, NPV, PPV of 73%, 72.5%, 72.7%, 76%, 69%. CONCLUSIONS: TV evaluated before and early after treatment could predict pathological response in LACC. ADCmean did not correlate with treatment outcome. KEY POINTS: • Early-MRI tumour volume assessment could predict pathological response to nCRT in LACC. • Best cut-off for predicting pathological PR was ΔTV reduction of 73 %. • Early-MRI ADC mean measurements did not correlate with treatment outcome.

PRospective Imaging of CErvical cancer and neoadjuvant treatment (PRICE) study: role of ultrasound to assess residual tumor in locally advanced cervical cancer patients undergoing chemoradiation and radical surgery.

OBJECTIVE: To determine the diagnostic performance of two-dimensional (2D) ultrasound parameters, three-dimensional (3D) power Doppler and contrast-enhanced indices in detecting residual disease in locally advanced cervical cancer patients triaged to neoadjuvant treatment followed by radical surgery. METHODS: Between October 2010 and June 2014, we screened 108 women with histologically documented locally advanced cervical cancer Stage IB2-IVA, of whom 88 were included in the final analysis. 2D ultrasound parameters, 3D power Doppler and contrast-ultrasound parameters were assessed 5 weeks after the end of neoadjuvant chemoradiation therapy. The pathological response was defined as complete (absence of any residual tumor after treatment) or partial (including microscopic and/or macroscopic residual tumor at pathology examination). The two response groups were compared and receiver-operating characteristics (ROC) curves generated to determine the best cut-off value of sonographic tumor diameter to predict residual disease. Histology was considered as reference. RESULTS: Complete pathological response to chemoradiation was observed in 40 (45.5%) patients and partial response in 48 (54.5%). The presence of residual disease, as confirmed at pathology examination, was detected by 2D grayscale ultrasound with a sensitivity of 64.6% and specificity of 65%. Color Doppler examination in the cases with lesions visualized on grayscale imaging detected the presence of residual disease, confirmed at pathology, with a sensitivity of 87.1% and specificity of 21.4%. The best area under the ROC curve (0.817) was for the detection of pathological residual disease of at least 6 mm in diameter, using a cut-off value of 12 mm for the largest tumor diameter assessed using 2D grayscale ultrasound (sensitivity, 95%; specificity, 70.6%). Neither 3D vascular indices nor contrast-ultrasound parameters obtained for lesions suspected at ultrasound following chemoradiation differed significantly between patients with histological complete and those with partial response. CONCLUSIONS: Our results show that grayscale and color Doppler ultrasound have a low level of diagnostic performance in detecting residual disease after neoadjuvant chemoradiation in patients with locally advanced cervical cancer. The best performance was achieved in detection of macroscopic (≥ 6 mm) residual disease. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

PRospective Imaging of CErvical cancer and neoadjuvant treatment (PRICE) study: role of ultrasound to predict partial response in locally advanced cervical cancer patients undergoing chemoradiation and radical surgery.

OBJECTIVE: Chemoradiation-based neoadjuvant treatment followed by radical surgery is an alternative therapeutic strategy for locally advanced cervical cancer (LACC), but ultrasound variables used to predict partial response to neoadjuvant treatment are not well defined. Our goal was to analyze prospectively the potential role of transvaginal ultrasound in early prediction of partial pathological response, assessed in terms of residual disease at histology, in a large, single-institution series of LACC patients triaged to neoadjuvant treatment followed by radical surgery. METHODS: Between October 2010 and June 2014, we screened 108 women with histologically documented LACC Stage IB2-IVA, of whom 88 were included in the final analysis. Tumor volume, three-dimensional (3D) power Doppler indices and contrast parameters were obtained before (baseline examination) and after 2 weeks of treatment. The pathological response was defined as complete (absence of any residual tumor after treatment) or partial (microscopic and/or macroscopic residual tumor at pathological examination). Complete-response and partial-response groups were compared and receiver-operating characteristics (ROC) curves were generated for ultrasound variables that were statistically significant on univariate analysis to evaluate their diagnostic ability to predict partial pathological response. RESULTS: There was a complete pathological response to neoadjuvant therapy in 40 (45.5%) patients and a partial response in 48 (54.5%). At baseline examination, tumor volume did not differ between the two groups. However, after 2 weeks of neoadjuvant treatment, the tumor volume was significantly greater in patients with partial response than it was in those with complete response (P = 0.019). Among the 3D vascular indices, the vascularization index (VI) was significantly lower in the partial-response compared with the complete-response group, both before and after 2 weeks of treatment (P = 0.037 and P = 0.024, respectively). At baseline examination in the contrast analysis, women with partial response had lower tumor peak enhancement (PE) as well as lower tumor wash-in rate (WiR) and longer tumor rise time (RT) compared with complete responders (P = 0.006, P = 0.003, P = 0.038, respectively). There was no difference in terms of contrast parameters after 2 weeks of treatment. ROC-curve analysis of baseline parameters showed that the best cut-offs for predicting partial pathological response were 41.5% for VI (sensitivity, 63.6%; specificity, 66.7%); 16123.5 auxiliary units for tumor PE (sensitivity, 47.9%; specificity, 84.2%); 7.8 s for tumor RT (sensitivity, 68.8%; specificity, 57.9%); and 4902 for tumor WiR (sensitivity, 77.1%; specificity, 60.5%). ROC curves of parameters after 2 weeks of treatment showed that the best cut-off for predicting partial pathological response was 18.1 cm3 for tumor volume (sensitivity, 70.8%; specificity 60.0%) and 39.5% for VI (sensitivity; 62.5%; specificity, 73.5%). CONCLUSIONS: Ultrasound and contrast parameters differ between LACC patients with complete response and those with partial response before and after 2 weeks of neoadjuvant treatment. However, neither ultrasound parameters before treatment nor those after 2 weeks of treatment had cut-off values with acceptable sensitivity and specificity for predicting partial pathological response to neoadjuvant therapy. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Agreement of two-dimensional and three-dimensional transvaginal ultrasound with magnetic resonance imaging in assessment of parametrial infiltration in cervical cancer.

OBJECTIVES: To compare two-dimensional (2D) and three-dimensional (3D) transvaginal ultrasound with magnetic resonance imaging (MRI) as the gold standard in assessment of parametrial infiltration of cervical cancer and to determine if all parts of the cervix are equally assessable with ultrasound. METHODS: Patients with macroscopically evident and histologically confirmed cervical cancer were staged using International Federation of Gynecology and Obstetrics (FIGO) criteria and underwent MRI and 2D and 3D ultrasound examination before treatment. When assessing parametrial infiltration with 3D ultrasound and MRI, the cervix was (virtually) divided into three cylinders (cranial, middle and caudal) of equal size and each cylinder was then divided into six sectors in a clockwise manner following a consensus between radiologists and ultrasound examiners. The presence and the extent of parametrial invasion were recorded for each sector. Results of 2D ultrasound, 3D ultrasound and MRI were compared and reported in terms of percentage agreement and kappa value. RESULTS: A total of 29 consecutive patients were included in the study. The percentage agreement between 2D ultrasound and MRI in assessing parametrial infiltration (yes or no) was 76% (kappa, 0.459) and that between 3D ultrasound and MRI was 79% (kappa, 0.508). The results of 2D ultrasound showed the following agreement with those of MRI: 90% for the ventral parametrium (kappa, 0.720), 72% for the right lateral parametrium (kappa, 0.494), 69% for the left lateral parametrium (kappa, 0.412) and 58.5% for the dorsal parametrium (kappa, 0.017). The results of 3D ultrasound showed the following agreement with those of MRI: 62.5% for the ventral parametrium (kappa, 0.176), 81% for the right lateral parametrium (kappa, 0.595), 70% for the left lateral parametrium (kappa, 0.326) and 52% for the dorsal parametrium (kappa, 0.132). The best agreement between 3D ultrasound and MRI was for the middle cervical cylinder (76%; kappa, 0.438) and the poorest agreement was for the caudal cylinder (42%; kappa, 0.125). CONCLUSION: The results of 2D and 3D ultrasound showed similar moderate agreement with MRI; 2D and 3D ultrasound examinations are less costly and more readily available than MRI and should be considered in the preoperative work-up for cervical cancer.

Transvaginal ultrasonography and magnetic resonance imaging for assessment of presence, size and extent of invasive cervical cancer.

OBJECTIVES: To prospectively assess the diagnostic performance of transvaginal ultrasound and magnetic resonance imaging (MRI), using histology as the gold standard, with regard to the presence, size, and extent of invasive cervical cancers and the detection of metastatic lymph nodes. METHODS: This was a prospective study designed to examine patients with invasive cervical cancer by means of ultrasonography and MRI within 1 week before surgery. We included patients with early cervical cancer planned for primary surgery and patients with locally advanced cervical cancer planned for surgery after neoadjuvant treatment. RESULTS: An invasive cervical cancer tumor was confirmed in the 33 patients triaged for primary surgery. A residual tumor mass was documented in 27 out of 35 patients (77%) who underwent surgery after neoadjuvant treatment, with no residual tumor in eight (23%) cases. Transvaginal ultrasound and MRI examinations showed the presence of the tumor mass in 56/60 (93%) and in 53/60 (88%) cases, respectively. Ultrasound and MRI detected the depth of stromal invasion to be greater than two-thirds with a sensitivity of 100% (16/16) and 94% (15/16) (P = 1) and a false-positive rate of 25% (13/52) and 15% (8/52) (P = 0.58), respectively. Both ultrasound and MRI provided low sensitivities (3/5, 60% and 2/5, 40% respectively, P = 1) and the same false-positive rate (7/63, 11%) for the presence of parametrial infiltration. One of the 11 patients with metastatic lymph nodes was detected at ultrasound examination (sensitivity 9%) with no false-positive cases, while MRI correctly identified three positive cases (sensitivity 27%, 3/11) with two false-positive cases (false positive rate 4%, 2/55). CONCLUSIONS: Ultrasound and MRI had similar sensitivity and specificity with regard to the parameters investigated. Ultrasound has the advantages over MRI of low cost, widespread availability and of being a relatively quick procedure. Ultrasound should be considered as a suitable diagnostic method in the preoperative work-up of cervical cancer.