Cervical Carcinoma: Can Dynamic Contrast-enhanced MR Imaging Help Predict Tumor Aggressiveness?

Purpose: This study tests whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameters obtained from canine patients with soft tissue sarcomas, treated with hyperthermia and radiotherapy, are predictive of therapeutic outcome. Experimental Design: Thirty-seven dogs with soft tissue sarcomas had DCE-MRI done before and following the first hyperthermia. Signal enhancement for tumor and reference muscle were fitted empirically, yielding a washin/washout rate for the contrast agent and tumor area under the signal enhancement curve (AUC) calculated from 0 to 60 seconds, 90 seconds, and the time of maximal enhancement in the reference muscle. These parameters were then compared with local tumor control, metastasis-free survival, and overall survival. Results: Pretherapy rate of contrast agent washout was positively predictive of improved overall and metastasis-free survival with hazard ratio of 0.67 (P = 0.015) and 0.68 (P = 0.012), respectively. After the first hyperthermia washin rate, AUC60, AUC90, and AUCt-max were predictive of improved overall and metastasis-free survival with hazard ratio ranging from 0.46 to 0.53 (P < 0.002) and 0.44 to 0.55 (P < 0.004), respectively. DCE-MRI parameters were compared with extracellular pH and 31 P MR spectroscopy results (previously published) in the same patients showing a correlation. This suggested that an increase in perfusion after therapy was effective in eliminating excess acid from the tumor. Conclusions: This study shows that DCE-MRI has utility predicting overall and metastasis-free survival in canine patients with soft tissue sarcomas. To our knowledge, this is the first time that DCE-MRI parameters are predictive of clinical outcome for soft tissue sarcomas. Numerous phase III clinical trials have shown that thermor-adiotherapy is superior to radiotherapy alone for achieving local tumor control and, in some cases, improving survival (1 -6). It is well known that hyperthermia changes tumor oxygenation, inhibits DNA damage repair, and is directly cytotoxic (7, 8). The effects described above are strongly dependent on temperature and duration of heat exposure, but which effect dominates in improving tumor control with thermoradiotherapy is not known. In preclinical models, mild to moderate heating (41-43jC) leads to increased perfusion and oxygenation, whereas higher thermal exposures can cause vascular damage and hypoxia (8). Presumably, this latter effect would be deleterious to optimal thermoradiotherapy response, but there are no definitive clinical studies showing this.Previous work with canine sarcomas have reported improved oxygenation following a single hyperthermia treatment when median temperatures were <44jC (9) and that changes in oxygenation can persist throughout a course of fractionated thermoradiotherapy (10). Milligan and Panjehpour (11) reported that perfusion was improved throughout a course of thermoradiotherapy in dogs with mast cell tumors. These data support the notion that part of the effect that mild hyperthermi...

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“…Several prior reports have shown correlations between DCE-MRI parameters and treatment outcome. (27, 29, 31, 39–41)…”

Section: Discussionmentioning

confidence: 99%

Dynamic Contrast-enhanced Magnetic Resonance Imaging as a Predictor of Clinical Outcome in Canine Spontaneous Soft Tissue Sarcomas Treated with Thermoradiotherapy

Viglianti

Lora-Michiels

Poulson

et al. 2009

Clinical Cancer Research

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“…Most centers choose a primary surgical approach in low-stage (lower than IIb) cervical cancer patients [3]. Patients with involvement of the parametria (higher than IIa), or with a large tumor diameter (>4 cm), receive first-line radiation therapy in most institutes [2,3,11,12,13]. When correlated with surgical staging, clinical staging for primary cervical cancer has an error rate of 26-66% [6,11,13].…”

Section: Discussionmentioning

confidence: 99%

“…Cervical carcinoma has intermediate signal intensity at T2-weighted images and is seen as a mass disrupting lowsignal-intensity fibrous cervical stroma [11]. Dynamic MR imaging technique after contrast injection has been reported to have no additional value in the tumor detection or evaluation of the extension of cervical carcinoma [11,12,16,17,18]. The cervical mass can demonstrate a wide variety of morphological features and may be exophytic, infiltrating, or endocervical [11].…”

Section: Discussionmentioning

confidence: 99%

The correlation of preoperative CT, MR imaging, and clinical staging (FIGO) with histopathology findings in primary cervical carcinoma

et al. 2003

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The aim of this study was to compare the preoperative findings of abdominal/pelvic CT and MRI with the preoperative clinical International Federation of Obstetrics and Gynecology (FIGO) staging and postoperative pathology report in patients with primary cancer of the cervix. Thirty-six patients with surgical-pathological proven primary cancer of the cervix were retrospectively studied for preoperative staging by clinical examination, CT, and MR imaging. Studied parameters for preoperative staging were the presence of tumor, tumor extension into the parametrial tissue, pelvic wall, adjacent organs, and lymph nodes. The CT was performed in 32 patients and MRI (T1- and T2-weighted images) in 29 patients. The CT and MR staging were based on the FIGO staging system. Results were compared with histological findings. The group is consisted of stage 0 (in situ):1, Ia:1, Ib:8, IIa:2, IIb:12, IIIa:4, IVa:6, and IVb:2 patients. The overall accuracy of staging for clinical examination, CT, and MRI was 47, 53, and 86%, respectively. The MRI incorrectly staged 2 patients and did not visualize only two tumors; one was an in situ (stage-0) and one stage-Ia (microscopic) disease. The MRI is more accurate than CT and they are both superior to clinical examination in evaluating the locoregional extension and preoperative staging of primary cancer of the cervix.

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“…There is controversy in the literature regarding the potential associations that may exist between histology and DCE-MRI findings in angiogenic-related pathologic processes. Whereas some studies have shown a positive correlation between tumor enhancement and microvascular density on histomorphometric assessment [30][31][32], other studies have shown no correlation [33][34][35]. Although we have used a semiquantitative scoring system rather than a histomorphometric procedure to quantify synovial vascularity, we postulate that microvascular density cannot be assumed to be the only determinant factor of tissue enhancement.…”

Section: Discussionmentioning

confidence: 87%

Dynamic Contrast-Enhanced MRI Quantification of Synovium Microcirculation in Experimental Arthritis

Doria

Noseworthy²,

Oakden³

et al. 2006

American Journal of Roentgenology

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Cervical Carcinoma: Can Dynamic Contrast-enhanced MR Imaging Help Predict Tumor Aggressiveness?

Abstract: Dynamic contrast-enhanced MR imaging does not facilitate differentiation between aggressive and nonaggressive tumors and therefore has no clinical role in assisting in treatment decisions in patients who are candidates for radical hysterectomy.

Cited by 30 publications

References 10 publications

Dynamic Contrast-enhanced Magnetic Resonance Imaging as a Predictor of Clinical Outcome in Canine Spontaneous Soft Tissue Sarcomas Treated with Thermoradiotherapy

Dynamic Contrast-enhanced Magnetic Resonance Imaging as a Predictor of Clinical Outcome in Canine Spontaneous Soft Tissue Sarcomas Treated with Thermoradiotherapy

The correlation of preoperative CT, MR imaging, and clinical staging (FIGO) with histopathology findings in primary cervical carcinoma

Dynamic Contrast-Enhanced MRI Quantification of Synovium Microcirculation in Experimental Arthritis

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