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Distant Metastasis

Distant metastasis in head and neck cancer—specifically head and neck squamous cell carcinoma (HNSCC)—is an ominous sign. While patients with certain cancer types who have distant metastases can live a long life (well-differentiated thyroid cancer, some adenoid cystic salivary gland carcinomas), many others will have complications related to the cancer. In general, the goal of managing distant metastasis is to try to prevent the tumor from growing and causing complications.

Certain tumor types are more likely than others to develop distant metastases. This includes adenoid cystic carcinoma, basaloid squamous cell carcinoma and neuroendocrine carcinomas (such as Merkel Cell carcinoma).1 Ferlito A, Shaha AR, Silver CE, Rinaldo A, Mondin V. Incidence and sites of distant metastases from head and neck cancer. O RL J Otorhinolaryngol Relat Spec. 2001;63(4):202-207.

The exact incidence of distant metastases in head and neck cancer is difficult to determine. Historically, there was a long-standing belief that the lymph nodes in the neck were a barrier preventing cancer from spreading throughout the rest of the body. This was based on autopsy studies of patients who died with HNSCC; in over 4000 autopsies, the rate of distant metastasis was less than 1 percent.2 Allen CT, Law JH, Dunn GP, Uppaluri R. Emerging insights into head and neck cancer metastasis. Head Neck. 2012 doi: 10.1002/hed.23202. [Epub ahead of print]. Whether the lymph nodes in the neck are a necessary step prior to cancer getting to distant sites is a matter of debate, and newer studies have shown that the rate of distant metastases can be as high as 25 to 50 percent in autopsy studies of patients with HNSCC.3, Merino OR, Lindberg RD, Fletcher GH. An analysis of distant metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer. 1977;40:145-151.4, Spector JG, Sessions DG, Haughey BH, et al. Delayed regional metastases, distant metastases, and second primary malignancies in squamous cell carcinomas of the larynx and hypopharynx. Laryngoscope. 2001;111:1079-1087.5, Nishijima W, Takooda S, Tokita N, Takayama S, Sakura M. Analyses of distant metastases in squamous cell carcinoma of the head and neck and lesions above the clavicle at autopsy. Arch Otolaryngol Head Neck Surg. 1993;119:65-68.6, Zbaren P, Lehmann W. Frequency and sites of distant metastases in head and neck squamous cell carcinoma: an analysis of 101 cases at autopsy. Arch Otolaryngol Head Neck Surg. 1987;113:762-764.7 Kotwall C, Sako K, Razack MS, Rao U, Bakamjian V, Shedd DP. Metastatic patterns in squamous cell cancer of the head and neck. Am J Surg. 1987;154:439-442.

According to a thorough analysis of the SEER database over many years, the following trends in stage at diagnosis of a few different types of head and neck cancers showed the following8 Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. International Journal of Cancer. 2004;114(5), 806-816.:

Site Percentage of patients with distant metastasis at diagnosis 1974 to 1999
Oral cavity 6%
Lip 0.6%
Salivary gland 16%
Oropharynx 13%
Nasopharynx 10%
Hypopharynx 19%
Larynx 16%
Other mouth/pharynx 19%

Over the past few decades, doctors have made big advancements in eliminating the main tumor and spread to lymph nodes in the neck, which is called locoregional control. However, long-term survival has not changed significantly. One possible reason for this is while locoregional control has gotten better, the rate of distant spread of the cancer has not changed (or may have even increased as patients with locoregional control live longer). As it stands, while local and regional control of head and neck cancer is necessary to achieve a cure, it is not sufficient. There is something inherent in particular tumors that makes them more likely to spread throughout the body.

References

1 Ferlito A, Shaha AR, Silver CE, Rinaldo A, Mondin V. Incidence and sites of distant metastases from head and neck cancer. O RL J Otorhinolaryngol Relat Spec. 2001;63(4):202-207.

2 Allen CT, Law JH, Dunn GP, Uppaluri R. Emerging insights into head and neck cancer metastasis. Head Neck. 2012 doi: 10.1002/hed.23202. [Epub ahead of print].

3 Merino OR, Lindberg RD, Fletcher GH. An analysis of distant metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer. 1977;40:145-151.

4 Spector JG, Sessions DG, Haughey BH, et al. Delayed regional metastases, distant metastases, and second primary malignancies in squamous cell carcinomas of the larynx and hypopharynx. Laryngoscope. 2001;111:1079-1087.

5 Nishijima W, Takooda S, Tokita N, Takayama S, Sakura M. Analyses of distant metastases in squamous cell carcinoma of the head and neck and lesions above the clavicle at autopsy. Arch Otolaryngol Head Neck Surg. 1993;119:65-68.

6 Zbaren P, Lehmann W. Frequency and sites of distant metastases in head and neck squamous cell carcinoma: an analysis of 101 cases at autopsy. Arch Otolaryngol Head Neck Surg. 1987;113:762-764.

7 Kotwall C, Sako K, Razack MS, Rao U, Bakamjian V, Shedd DP. Metastatic patterns in squamous cell cancer of the head and neck. Am J Surg. 1987;154:439-442.

8 Carvalho AL, Nishimoto IN, Califano JA, Kowalski LP. Trends in incidence and prognosis for head and neck cancer in the United States: a site-specific analysis of the SEER database. International Journal of Cancer. 2004;114(5), 806-816.

9 Leemans CR, Tiwari R, Nauta JJ, van der Waal I, Snow GB. Regional lymph node involvement and its significance in the development of distant metastases in head and neck carcinoma. Cancer. 1993;71(2):452-456.

10 Alvi A, Johnson JT. Development of distant metastasis after treatment of advanced-stage head and neck cancer. Head Neck. 1997;19(6):500-505.