Clinical Investigation
Dynamic Contrast-Enhanced Magnetic Resonance Imaging as a Predictor of Outcome in Head-and-Neck Squamous Cell Carcinoma Patients With Nodal Metastases

https://doi.org/10.1016/j.ijrobp.2011.03.006Get rights and content

Purpose

Dynamic contrast-enhanced MRI (DCE-MRI) can provide information regarding tumor perfusion and permeability and has shown prognostic value in certain tumors types. The goal of this study was to assess the prognostic value of pretreatment DCE-MRI in head and neck squamous cell carcinoma (HNSCC) patients with nodal disease undergoing chemoradiation therapy or surgery.

Methods and Materials

Seventy-four patients with histologically proven squamous cell carcinoma and neck nodal metastases were eligible for the study. Pretreatment DCE-MRI was performed on a 1.5T MRI. Clinical follow-up was a minimum of 12 months. DCE-MRI data were analyzed using the Tofts model. DCE-MRI parameters were related to treatment outcome (progression-free survival [PFS] and overall survival [OS]). Patients were grouped as no evidence of disease (NED), alive with disease (AWD), dead with disease (DOD), or dead of other causes (DOC). Prognostic significance was assessed using the log-rank test for single variables and Cox proportional hazards regression for combinations of variables.

Results

At last clinical follow-up, for Stage III, all 12 patients were NED. For Stage IV, 43 patients were NED, 4 were AWD, 11 were DOD, and 4 were DOC. Ktrans is volume transfer constant. In a stepwise Cox regression, skewness of Ktrans (volume transfer constant) was the strongest predictor for Stage IV patients (PFS and OS: p <0.001).

Conclusion

Our study shows that skewness of Ktrans was the strongest predictor of PFS and OS in Stage IV HNSCC patients with nodal disease. This study suggests an important role for pretreatment DCE-MRI parameter Ktrans as a predictor of outcome in these patients.

Introduction

The American Cancer Society estimated that in 2010 approximately 49,260 new cases of oral cavity, pharyngeal, and laryngeal cancers would be diagnosed and that 11,480 deaths would occur from these cancers in the United States (1). Treatment for advanced (Stage III or IV) head and neck squamous cell carcinoma (HNSCC) usually consists of combined chemoradiation therapy or complete surgical resection followed by adjuvant chemotherapy and/or radiation therapy 2, 3, 4, 5. Despite advances in the treatment options available, the overall survival rate of HNSCC patients with advanced disease has not improved substantially over the past decade (6). Thus, an a priori predictor of outcome could prove extremely valuable by allowing oncologists to intervene with alternative therapies if necessary.

Reported tumor-based prognostic factors for locoregional control of HNSCC include the presence and extent of nodal metastases, T-stage, tumor site, tumor size, human papilloma virus (HPV) tumor positivity, and other biological markers 7, 8, 9, 10. In advanced HNSCC, the T stage and nodal disease at initial presentation are the most important predictors of outcome (8). The use of individual and combined markers to predict outcome in HNSCC has shown conflicting results. For example, various investigators have recorded different degrees of correlation between tumor suppressor gene p53 status and outcome 11, 12, 13. Epidermal growth factor receptor (EGFR) overexpression has been shown to correlate strongly with advanced tumor stage, shorter disease-free survival, and overall survival in HNSCC (14). Recently, HPV-positive HNSCC has been shown to respond to treatment better than non-HPV-positive HNSCC (15). Preliminary evidence supports the potential role of such biomarkers in disease management, but their value needs to be tested in prospective validation studies (7).

Noninvasive measurement of tumor perfusion and permeability using gadopentetate dimeglumine (Gd-DTPA)-based dynamic contrast-enhanced MRI (DCE-MRI) has shown promise in predicting treatment response and outcome in selected tumors 16, 17, 18, 19, 20, 21. DCE-MRI involves assessing changes in signal intensity over time. With proper quantitative analysis, the data may provide parameters reflecting tumor-vessel permeability, tumor perfusion, and extracellular-extravascular volume fraction 22, 23, 24, 25. Studies have suggested that DCE-MRI parameters such as Ktrans (volume transfer constant) and primary tumor blood volume (BV) may predict early response in HNSCC patients treated with chemoradiation 20, 26. This study aimed to assess the prognostic value of pretreatment DCE-MRI parameters in HNSCC patients with nodal disease undergoing chemoradiation therapy or surgery.

Section snippets

Patient selection

The institutional review board (IRB) granted a waiver of informed consent for this retrospective study that included 74 patients with histologically proven squamous cell carcinoma (SCC) and neck nodal metastases. Their clinical characteristics are listed in Table 1. Of 74 patients, 61 had primary treatment with chemoradiation and 13 underwent surgery (Table 1). Patients received treatment as per standard guidelines 4, 5, 27, 28 (see Table 2 for details).

DCE-MRI methodology

All patients had a baseline DCE-MRI

Results

All 12 clinical Stage III patients were NED at last clinical follow-up. Of the clinical Stage IV patients, 43 were NED, 4 were AWD, 11 were DOD, and 4 were DOC at last clinical follow-up. The average pretreatment values for the median, standard deviation, and skewness of Ktrans, ve, and kep for Stage III and Stage IV patients are provided in Table 3. Figure 1 shows representative pretreatment DCE-MRI data. Figure 2 shows representative case of HPV positive and negative staining. Patterns of

Discussion

The data in this study indicate that lower skewness (i.e., less asymmetry in the distribution) of Ktrans may be predictive of better outcome in HNSCC patients with Stage IV nodal disease. There is overwhelming evidence that tumors are heterogeneously perfused (33). Imaging vascular heterogeneity by DCE-MRI has been shown to be useful for understanding tumor biology and predicting outcome (34). Jackson et al. (34) reported that tumor heterogeneity is better reflected by the distribution of the

Conclusion

Skewness of Ktrans was a strong predictor of progression-free survival and overall survival in HNSCC patients with Stage IV nodal disease. This finding suggests an important role for this pretreatment DCE-MRI parameter as a predictor of outcome in HNSCC patients with advanced disease.

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    This study was funded by the National Cancer Institute/National Institutes of Health (Grant No. 1 R01 CA115895). We thank Ada Muellner for editing the manuscript.

    Conflict of interest: none.

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