Abstract
Aim: Patients with cerebral metastases from head and neck cancer are not common. This study aimed to create an instrument for estimating survival in this particular group of patients. Patients and Methods: Survival was significantly influenced by Eastern Cooperative Oncology Group (ECOG) performance score, number of cerebral lesions and extracranial metastatic disease. These characteristics were included in our score. Results: Scoring was based on 6-month survival data: ECOG 0-1=1 point, ECOG 2-3=0 points, 1-3 cerebral lesions=1 point, ≥4 cerebral lesions=0 points, lack of extracranial metastases=1 point, and presence of extracranial metastases=0 points. Addition of these points for each patient resulted in 0-3 points. Three groups were built comprising 0-1, 2 and 3 points. Six-month survival rates for these groups were 0%, 50% and 100%, respectively. Conclusion: This new instrument guides physicians in choosing optimal irradiation programs for patients with cerebral metastases from head-and-neck cancer.
Patients with locally advanced head and neck cancer have a poor prognosis, which applies particularly to patients with metastatic disease including brain metastases (1). Because patients with head and neck cancer represent a small group of patients with cerebral metastases, the optimal treatment approach for individual patients is often not properly defined for this sub-group. Treatment decision processes could be facilitated with an instrument that allows treating physicians to estimate the patient's life expectancy. Knowledge of the remaining lifetime will affect the selection of appropriate regimen, including local treatments such as neurosurgery or radiosurgery, as well as whole-brain irradiation (WBI) programs (2, 3). Such knowledge can be gained from predictive tools. Because primary tumors, particularly in a metastasized situation, are different with respect to tumor biology, metastatic pattern, and prognosis in general, each primary tumor type requires its own prognostic instrument (4, 5). The current study was performed to create such an instrument specifically for patients with cerebral metastases from head and neck cancer.
Patients and Methods
In this study, the data of 25 patients treated with WBI for cerebral metastases from head-and-neck cancer between 2000 and 2014 were analyzed. The WBI dose (4 Gy ×5 versus 3 Gy ×10 versus 2 Gy ×20) plus the following seven additional characteristics were analyzed for associations with post-WBI survival: age (≤64 versus ≥65 years, median age=64 years), gender, Eastern Cooperative Oncology Group (ECOG) performance score (0-1 versus 2-3), primary tumor site (nasopharynx versus oropharynx versus hypopharynx versus larynx versus parotid glands versus oral cavity/floor of mouth), time between first diagnosis of head-and-neck cancer and WBI (≤24 versus ≥25 months, median time=24 months), number of cerebral lesions (1-3 versus ≥4 lesions), and the presence of extracranial metastases (no versus yes). The distributions of all eight characteristics are shown in Table I.
The survival analysis was performed with the Kaplan–Meier method, and the p-values were obtained from the log-rank test. The characteristics which achieved significance were included in the predictive instrument. For each significant characteristic, a score of 0 (unfavorable survival prognosis) or 1 (favorable survival prognosis) was given. The prognostic score for each patient was calculated by adding the scores for the significant prognostic factors.
Patients' characteristics.
Results
In the survival analysis, three of the investigated characteristics, namely ECOG performance score, number of cerebral lesions and presence of extracranial metastases, had a significant impact on survival. The results of the analysis of survival are given in Table II. The scores obtained for the three characteristics found to be significantly associated with survival were as follows: ECOG 0-1=1 point, ECOG 2-3=0 points, 1-3 cerebral lesions=1 point, ≥4 cerebral lesions=0 points, lack of extracranial metastases=1 point and presence of extracranial metastases=0 points. The addition of the scores of the three characteristics resulted in prognostic scores of 0 to 3 points (n=12, n=3, n=2 and n=8 for scores of 0, 1, 2 and 3, respectively). The 6-month survival rates related to these scores were 0%, 0%, 50% and 100%, respectively (p=0.002). Based on these scores, the following three survival groups were built: 0-1 points, 2 points and 3 points. The corresponding 6-month survival rates were 0%, 50% and 100%, respectively. The corresponding 12-month survival rates were 0%, 0% and 63%, respectively.
Characteristics and corresponding survival rates at six and 12 months.
Discussion
In order to improve the prognosis of patients with head-and-neck cancer, considerable efforts have been made in recent years, for example by introducing new anticancer therapies (6-8). Another approach for improving the treatment results is the individualization of therapeutic approaches by including prognostic factors into treatment decisions (9-13). Knowing a patient's survival time is a very important aspect with respect to optimal individualization of their treatment. This applies particularly to patients with metastatic disease. Patients with brain metastases require particular attention, since many of these patients develop serious symptoms such as seizures, visual disorders, signs of paralysis and character changes (1). Therefore, survival tools have been developed for these patients in general and, in addition, specifically for single tumor entities (5, 14-17). However, a specific score for patients with cerebral metastases from head-and-neck cancers has been lacking.
In the present study, such a score was created. Three significant prognostic factors were identified: ECOG performance score, number of cerebral lesions and presence of extracranial metastatic disease. Our new predictive instrument was based on these three characteristics and allowed the building of three groups with 6-month survival rates of 0% (0-1 points), 50% (2 points) and 100% (3 points). Since the prognosis of patients with 0-1 points is extremely poor, these patients should ideally receive a short WBI program such as 4 Gy ×5 in one week to avoid spending more time than necessary receiving treatment. This recommendation is supported by a study of patients with cerebral metastases from different tumor entities that reported similar survival rates after 4 Gy ×5 and after 3 Gy ×10 (24% and 27%, respectively; p=0.29) (18). In the group of patients with only 0-1 points, even best supportive care alone may be an option. Patients who achieve 2 points are suitable candidates for the most commonly used WBI program worldwide of 3 Gy ×10 (1). Patients with 3 points have a much more favorable survival prognosis and could benefit from a WBI program with a total dose of greater than 30 Gy and a dose per fraction of less than 3 Gy (19, 20). A total dose beyond 30 Gy was reported to result in improved 1-year intracerebral control rates (44% vs. 28%, p=0.06) and improved 1-year survival rates (61% vs. 50%) when compared to 3 Gy ×10 (19). Furthermore, doses per fraction of less than 3 Gy are associated with less neurocognitive decline than doses of ≥3 Gy (20). Patients with 3 points and a limited number of cerebral lesions might also be considered for more intensive local treatment, including resection, radiosurgery or fractionated stereotactic radiotherapy (2, 3).
In conclusion, this new score for patients with cerebral metastases from head-and-neck cancer contributes to the selection of optimal personalized treatment approaches.
Footnotes
Conflicts of Interest
On behalf of all Authors, the corresponding Author states that there is no conflict of interest related to this study.
- Received May 26, 2015.
- Revision received July 3, 2015.
- Accepted July 7, 2015.
- Copyright © 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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