Abstract
Background/Aim: In addition to locoregional recurrence distant metastases can limit the survival of patients with head and neck cancer. The aim of the study was to analyze survival after distant metastasis of head and neck cancer. Patients and Methods: Patients with head and neck cancer and M0 status at initial diagnosis, who were treated with curative intent but developed distant metastases without synchronous locoregional recurrence were analyzed. Predictors for the duration of survival were evaluated using Cox regression analysis. Results: A total of 46 patients developed distant metastases which were detected after a mean time of 16 months, most were lung (59%) and bone metastases (24%). The most common therapy for distant metastasis was palliative chemotherapy; due to poor general condition, 21% of patients were treated with best supportive care. The mean survival was 7.5 months, the overall survival at 1 and 2 years after diagnosis of distant metastasis were 40.4% and 26.2%, respectively. Regression analysis showed no significant predictors for prolonged survival, however, the three patients surviving at the time of data collection were treated by surgical resection of solitary metastases. Conclusion: In cases of distant metastases, due to poor prognosis of the patients, palliation is important and the treatment approach should be chosen taking into account the general condition of the patient. In individual cases, resection of solitary metastases may be useful.
Nearly 60% of patients with head and neck squamous cell carcinoma present with locoregionally advanced, stage III and IV disease (1). Although locoregional control has been improved due to treatment with radiochemotherapy compared to radiotherapy-alone, the failure rate at distant organs remains high. The rate of distant metastasis in patients with head and neck squamous cell carcinoma ranges between 4% and 26% (2, 3). Different risk factors for the development of distant metastasis, such as primary site, tumor differentiation, and nodal involvement, especially of level IV, have been identified and discussed in several studies (4, 5). The optimal treatment strategy for patients with distant metastasis remains unclear. The aim of this study was to analyze survival after detection of distant metastasis in patients with head and neck cancer with initial M0 status.
Patients and Methods
Patients with squamous cell carcinoma of the upper aerodigestive tract with initial M0 status treated with curative intent from 2005-2012 and who developed distant metastases without synchronous locoregional recurrence were retrospectively analyzed regarding sex, tumor characteristics, localization of metastases, therapy and outcome.
The diagnosis of distant metastasis was based on clinical or positive findings on contrast-enhanced computed tomographic or magnetic resonance imaging or fluorodeoxyglucose positron emission tomography and tissue biopsy. Clinical staging and treatment choices were decided using the information derived from these examinations at the Head and Neck Cancer Board which consisted of head and neck surgeons, maxillofacial surgeons, radiation oncologists, medical oncologists, radiologists and pathologists. When this study was completed, three patients were still alive.
Statistical analysis. Survival times were calculated from the diagnosis of distant metastasis. The Kaplan–Meier method was used to examine overall survival. Cox regression analysis was used to analyze the prognostic value of patient and clinical characteristics in terms of overall survival.
Results
Out of the 46 patients who developed distant metastases, 41 were men and five were women. The mean age at primary diagnosis was 58.1 years (range=37-80 years), and the mean age at diagnosis of distant metastasis was 59.5 years (range=38-80 years). Characteristics of the primary tumors are shown in Table I. The primary tumors were treated by primary chemoradiation in 22 cases, by surgery and adjuvant (chemo)radiation in 23 cases, and by surgery-alone in one case.
The mean time from initial diagnosis to distant metastasis was 16 months, the maximum interval to detection of distant metastases was 4.1 years. Lung metastases (59%) and bone metastases (24%) occurred most frequently (Figure 1). The majority of patients with lung metastases had no symptoms; lung metastases were detected in routine surveillance imaging of the chest in most of the cases. The most common symptom of bone metastasis that caused patients to seek treatment was localized bone pain. Single-site distant metastases were present in 12 patients (26%). Single-site metastasis were mainly pulmonary (seven cases) followed by bone (four cases) and liver (one case). The other 34 patients had multiple metastatic sites.
The most common therapy for distant metastases was palliative chemotherapy. Regarding the entire cohort of patients, 10 (21.7%) received single chemotherapy and 16 (34.8%) received combined chemotherapy after diagnosis of distant metastasis. Platinum-based combination regimens were the ones most widely used. In eight patients (17.4%), bone metastases were treated by radiotherapy. Three patients underwent surgical metastasectomy of solitary metastases and were still alive at the time the study was completed. One underwent a craniotomy for a solitary brain metastasis, while the other two patients underwent thoracoscopic wedge resection of solitary pulmonary metastases. Best supportive care was provided due to poor general condition in 21% of the patients.
The mean survival time after diagnosis of distant metastases was 7.5 months. The 1- and 2-year overall survival rates after diagnosis of distant metastasis were 40.4% and 26.2%, respectively, considering the entire cohort of patients (Figure 2). Cox regression analysis showed no significant predictors for prolonged survival, however, the three patients surviving at the time of data collection were treated by surgical resection of solitary metastases. The localization of distant metastasis and the development of single-site versus multiple sites of distant metastasis were not predictive of a higher life expectancy. The mean follow-up after diagnosis of distant metastasis for the three patients who remained alive was 62.1 months.
Discussion
Patients developing distant metastases after treatment of head and neck cancer with curative intent have a poor prognosis and short life expectancy. Previous studies showed that the median survival from the development of distant metastasis rarely exceeds 6 months (6) and that up to 90% of patients die within the first 12 months after diagnosis of distant metastasis (7). There are currently no standards on screening for distant metastasis, although it would seem to be useful as it allows for prognostication and adaptation of patient counseling and, in the case of early detection, the impact on prognosis of patients may be beneficial. Moreover, a need exists to define high-risk groups of patients so that intensive adjuvant therapy can be given when the initial diagnosis is confirmed. Identifying these high-risk groups for distant metastasis also helps head and neck oncologist to pay attention to symptoms that suggest the possibility of metastasis.
Characteristics of the primary tumors included in this study.
Previous reports revealed that distant metastases from head and neck squamous cell carcinoma occur in the lungs in up to 90% of cases (8) and that distant disease restricted to other sites is rare in the absence of simultaneous lung metastasis (9). Therefore, control for distant disease is mainly focused on the lungs in patients with head and neck carcinoma, and metastasis to other sites is typically not as closely monitored. In the present study, only 59% of the patients suffered from lung metastasis. As a result, it should be considered whether isolated screening of the lung makes sense, or whether routine surveillance imaging should also include the skeleton.
Furthermore, it is unclear whether all types of distant metastasis have the same prognosis. For this reason, the metastatic site currently has little impact on therapeutic management. In the present study, there was no difference in survival between patients with different metastastic sites; however, the analyzed patient cohort was small.
Distribution of distant metastases from head and neck cancer.
The chance of cure for patients with head and neck cancer who developed distant metastasis is very low. Palliative chemotherapy is the most frequently used treatment, although response rates are not satisfying. Studies showed that palliative chemotherapy can prolong the median survival of patients with distant metastasis (9, 10). However, due to the short life expectancy of such patients, due to the unclear benefit of chemotherapy and to chemotherapy-induced toxicities, treatment remains controversial. Moreover, patients must be healthy enough at diagnosis of distant metastasis in order to receive chemotherapy. Radiotherapy is typically used to treat single metastases to relieve symptoms caused by them or to avoid further complications.
Resection of solitary metastases in patients with head and neck cancer is controversial. The cases discussed in the present study suggest that a surgical approach to a solitary metastasis of head and neck cancer may prolong survival in certain patient sub-groups. Several reports exist of prolonged survival after surgical resection of solitary metastases in patients with head and neck cancer (11, 12). Hence, in patients with a good performance status, a treatment approach with curative intent, including surgical interventions, could be tried. However, as long as the impact of solitary metastasis remains unclear, screening programs for distant metastasis will not be established.
Standard treatment strategies for metachronous distant metastatic disease in head and neck cancer have not yet been established because of the limited number of cases. Therefore, randomized controlled studies are needed to implement a treatment strategy for such patients.
The limitations of our study were that it was a retrospective, non-randomized study which was conducted at a single center, and that the prevalence of human papilloma virus was unknown. Moreover, due to the retrospective nature of the study, patients with a longer survival may have received multiple regimens and long-term treatments.
Survival after diagnosis of distant metastasis from head and neck cancer.
Conclusion
In summary, the lung is the most frequent site when patients present with distant metastases after treatment of head and neck cancer with curative intent. Most patients have multiple metastases; in cases of a single metastasis, long-term survival is possible. Prospective randomized studies are required to optimize treatment strategies.
- Received May 30, 2015.
- Revision received July 14, 2015.
- Accepted July 16, 2015.
- Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved
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