Discussion
In this study, the incidence of lung metastases among patients with
newly diagnosed hypo-pharyngeal cancer was calculated. We found that
there was no significant difference in the incidence of lung metastases
in the primary site of the tumor. Unsurprisingly, females were less
likely to have lung metastases. Since many of the female patients’ lung
metastases status at diagnosis was unknown, not applicable or did not
record follow-up times and these patients were excluded, the true
incidence of lung metastases in female patients with hypo-pharyngeal
cancer is likely underestimated by the results of this study. In
addition, we are pleased to report for the first time that for each 10
mm increase in tumor size, the odds of having lung metastases increases
by 6.6%. This result may allow us to further predict the probability of
lung metastases based on tumor size. High histological grade III/IV had
the highest incidence of lung metastases in this study and was
consistent with the common knowledge. Moreover, we discovered that
patients with lung metastases were more likely to have other metastases.
This suggests that when we find lung metastases, we should perform
further tests such as: MRI, B-ultrasound and bone scan to exclude the
possibility of other metastases. The development of PET-CT makes finding
other metastases sites such as the aforementioned ones, much simpler.
Since hypo-pharyngeal cancer has a relatively lower incidence rate,
research is scant on the topic of lung metastases of this cancer. Even
research on head and neck squamous cell cancer is rare. Ampil, et
al3. reported 37 patients with treated head and neck
cancer had lung metastases, but did not mention the incidence rate. Marc
Mareel, et al 4reported incidences of lung metastases
in head and neck cancer patients at 10.8% of all the studied patients
and 78% of all distant metastasis patients. They also found that the
prevalence of distant metastases in hypo-pharyngeal cancer was 20.5%.
This result was somewhat different from our study. The incidence of lung
metastases in the Mareel study was only 4.7% of all the studied
patients and the incidence of all distant metastases was 6.3% in this
study. This discrepancy may be because the Mareel study only sampled
from a single center’s study and did not focus on hypo-pharyngeal
cancer. Our study using SEER data includes approximately 30% of the
United States population, the incidence proportions we describe are
highly generalizable and more likely to be reflective of the population
compared to previously published data focused primarily on patients
treated at academic cancer centers. Macherey, et al5.
performed a meta-analysis/review of all papers published between 2000
and 2014; they found lung metastases develop in 1.9-13% of head and
neck cancer patients. The results of our study seem agree with
Macherey’s findings.
The study conducted by Marc Mareel, et al also showed 47% of patients
died from their primary tumors during follow-up of which 52% of
patients had distant metastases, however the tumor site and distant
metastases site were not separated in Mareel’s study. In our study only
28.1% of patients died as a result of their first tumor; of those
individuals, 57.8% of patients had lung metastases. Compared to
Mareel’s study, our study focused on hypo-pharyngeal cancer and lung
metastases; it can truly illustrate the effect lung metastases of
hypo-pharyngeal cancer has on survival. P. Pracy, et al. reported the
overall 5-year disease specific survival rate in hypo-pharyngeal cancer
patients as approximately 30–35% in the United Kingdom. By reviewed
articles of head and neck cancer, Macherey, et al. reports a 58% 5-year
survival rate 5. In our study, 71.9% of patients were
alive or succumbed to other causes instead of the first tumor after the
5-year follow-up. The reported 2-years over survival(OS) in head and
neck cancer with distant metastases was 15% in Belgium, while in our
study, survival was close to 40% in hypo-pharyngeal cancer patients
with lung metastases and the survival probability gradually decreased to
20% after the 5-year follow-up. Our results were slightly different
from the studies in the United Kingdom and Belgium, because the
population composition may be different in three countries. A study
including a broader range of countries could account for this
discrepancy4,6.
As is shown in previous studies, a lot of risk factors will affect
survival time in head and neck cancer7. Among the
entire cohort, although the tumor primary site in the pyriform sinus
didn’t have significantly lower odds of lung metastases, they indicate a
lower risk associated with all-caused mortality (HR:0.83, 95%
CI:0.69-1.00, P =0.048). This suggests that the primary site of
tumor is still worthy of further research. African Americans not only
have significantly greater odds of lung metastases, but also suggests a
higher risk associated with all-caused mortality(HR:1.89, 95%
CI:1.49-2.40, P <0.001). This finding presents a bad
prognosis for African Americans who are diagnosed with hypo-pharyngeal
cancer. Tumor size is an undoubted risk factor for mortality, for each
10 mm tumor size increase, the risk of death increases by 3.9%. It
suggests that a closer follow-up study is needed for patients with
larger tumors.
Lung metastases is often caused by cancers of peritoneal organs,
including gastric cancer, colon cancer, pancreatic/biliary cancer,
ovarian cancer, and uterine cancer8. Most of these
cases are adeno-carcinomas; only a few cases are derived from squamous
cell cancer9-12. In contrast to these studies, we
found more patients having lung metastases with newly diagnosed
hypo-pharyngeal cancer. We revealed that race, histological grade and
tumor size were associated with having lung metastases at diagnosis. In
the future we should be wary of these factors.