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Nasopharyngeal cancer in Newfoundland

and Labrador: 7-year experience
Dawn Armstrong MD; Erin Powell MD; Melanie Seal MD; Stewart Rorke MD; Kara Laing MD;
Pradip Ganguly MD; Craig Pochini MD; Farah McCrate MSc; Joy McCarthy MD

Purpose: Nasopharyngeal cancer (NPC) is a rare malignancy also seen in 10 patients. Twenty-two patients (68.8%) were
in Newfoundland and Labrador (NL), and little is known disease-free 12 months after diagnosis, half of these pre-
about risk factors and preferred treatment in this unique senting with Stage IV at diagnosis. As of September 2010,
patient population. The purpose of this study is to review 20 patients (62.5%) were alive.
outcomes of NPC patients in NL and determine if these Median disease-free survival (DFS) and overall survival
outcomes are associated with stage at diagnosis and/or (OS) were greatest in Stage II patients, at a median of 39
treatment given. and 50 months, respectively. Finally, when comparing OS
by treatment, patients who had chemoradiation did better
Methods: This retrospective chart review includes all patients than those with radiation alone (42 vs 21 months).
seen at the Dr. H. Bliss Murphy Cancer Centre from 2002
to 2009 who were diagnosed with Stage I–IV NPC. Conclusion: Our findings show that the majority of patients
Patients received either radiation alone or concurrent with NPC in NL present at an advanced stage, and as expected,
chemoradiation. Information collected included patient outcomes are worse for more advanced stages at presentation.
demographics, treatment received, recurrence and survival In our cohort, no significant difference in OS was seen
outcomes. Outcomes were then compared based on stage between patients treated with radiation only vs those treated
and treatment (concurrent chemoradiation vs radiation alone). with chemoradiation. However, Stage III and IV patients
had longer OS with the addition of chemotherapy to radiation
Results: Out of 37 patients identified using the provincial treatment. Future studies should target differences in sub-
tumour registry, 32 cases met our criteria. Sixteen patients populations based on World Health Organization (WHO)
(50.0%) presented as Stage IV. Local recurrence was docu- type, ethnicity, Epstein-Barr virus (EBV) status and other
mented in 10 patients (31.3%), and metastatic disease was risk factors for NPC.

Nasopharyngeal cancer, Newfoundland and Labrador

Nasopharyngeal cancer (NPC) is a rare and understudied
form of cancer. In Canada, there were only 228 new
reported cases in 2005, making it a mere 0.3% of total new
cancer cases.1 Similarly, in the US2 and UK,3 NPC accounts
Dawn Armstrong, MD is an Internal Medicine Resident at for only about 1 out of every 1000 diagnosed cancers.
Memorial University, Newfoundland. Email:; Interestingly, in Asia, rates of NPC are estimated as high
Erin Powell, MD, FRCPC is a Clinical Assistant Professor in as 21 in 1000 men, pointing to an undetermined interplay
Medical Oncology at Memorial University; Melanie Seal, MD, of both environmental and genetic factors.4,5 Because of its
FRCPC is an Assistant Professor of Medical Oncology at Memorial low incidence, little is known about the risk factors for
University; Stewart Rorke, MD, FRCPC is a Clinical Assistant developing NPC in North America.6
Professor in Medical Oncology at Memorial University; Kara Laing, NPC is also characterized by its poor prognosis. Like many
MD, FRCPC is an Associate Professor of Medical Oncology at other cancers, prognosis is related to stage at diagnosis,
Memorial University; Pradip Ganguly, MD, FFRCSI is a Clinical with worse prognosis at higher stages.7 NPC is divided into
Associate Professor of Radiation Oncology at Memorial University; 4 stages using the American Joint Committee on Cancer
Craig Pochini, MD, FRCPC is a Clinical Assistant Professor of (AJCC) designated staging by TNM classification. Because of
Radiation Oncology at Memorial University; Farah McCrate, its anatomic location and often vague presenting symptoms,
MSc, PhD candidate at Memorial University, contributed to the most NPC cases are diagnosed at Stages III and IV.
statistical analysis for this article; Joy McCarthy, MD, FRCPC is a Standard treatment for NPC includes high-dose external
Clinical Assistant Professor in Medical Oncology at Memorial University. beam radiation therapy, with the addition of cisplatin-based

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e-4 oe VOL. 10, No. 2, may 2011
chemotherapy in later-stage and/or node-positive disease. Methods
Surgery can also be an option for nonresponding disease or We conducted this retrospective chart review in accordance
locoregional recurrence, according to the BC Cancer Agency with the Memorial University of Newfoundland Human
(BCCA) Protocol, 20098 and National Cancer Institute, 2009.9 Investigation Committee ethical research guidelines. A total
However, there is a paucity of randomized controlled clinical of 37 patients with Stage I–IV NPC who received either
data relating to treatment of NPC, and optimal regimens radiation alone or chemoradiation between 2002 and 2009
differ somewhat among major centres and are often based were identified from the Newfoundland and Labrador (NL)
on centre-specific data. This study will add to the limited
outcomes data available for NPC.
Table 3. Patient outcomes
Local recurrence
Table 1. Patient characteristics (n=32)
Stage I 1
Stage II 1
Male 22 (68.8%)
Stage III 4
Female 10 (31.3%)
Stage IV 4
Median age at diagnosis
Total 10 (31.3%)
56 years (range 18–78)
Smoking history
Stage I 1
Yes 23 (71.9%)
Stage II 0
No 9 (28.1%)
Stage III 4
History of alcohol use
Stage IV 5
Yes 25 (78.1%)
Total 10 (31.3%)
No 5 (15.6%)
Number still living*
Unknown 2 (6.3%)
Stage I 1
Stage II 7
Table 2. Tumour characteristics Stage III 3
Stage IV 9
WHO histologic type
Total 20 (62.5%)
I (squamous cell carcinoma) 25 (78.1%)
Median DFS*
II (nonkeratinizing carcinoma) 0 (0%)
Stage I 24.5 months (range 7–42)
III (undifferentiated carcinoma) 7 (21.9%)
Stage II 39.0 months (range 15–70)
Primary tumour (T) classification
Stage III 14.0 months (range 3–74)
T1 10 (31.3%)
Stage IV 13.0 months (range 2–48)
T2 9 (28.1%)
12 month DFS*
T3 2 (6.3%)
Stage I 1
T4 12 (37.5%)
Stage II 7
Regional lymph node (N) classification
Stage III 4
N0 8 (25.0%)
Stage IV 10
N1 6 (18.8%)
Total 22 (68.8%)
N2 13 (46.9%)
Median OS by AJCC Stage*
N3 5 (15.6%)
Stage I 34.5 months (range 27–42)
AJCC Stage
Stage II 50.0 months (range 15–72)
I 2 (6.3%)
Stage III 14.0 months (range 3–74)
II 7 (21.9%)
Stage IV 25.0 months (range 2–48)
III 7 (21.9%)
AJCC=American Joint Committee on Cancer
IV 16 (50.0%)
DFS=disease-free survival OS=overall survival
AJCC=American Joint Committee on Cancer WHO=World Health Organization *as of September 2010

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oe VOL. 10, No. 2, may 2011 e-5
Cancer Registry at the Dr. H. Bliss Murphy Cancer Centre
(HBMCC). Staging was based on the AJCC Cancer Staging Table 5. Overall survival (months), by treatment
Manual, 7th Ed,10 and treatment was decided by our centre’s and stage at time of diagnosis
multidisciplinary team based on staging, pathologic features, Radiation Only Chemoradiation
medical comorbidities and patient preference.
Stage I 42 27
Two patients were excluded because their final diagnosis
did not meet the World Health Organization (WHO) defi- Stage II 72, 50, 15 (median=50.0) 70, 36, 54, 39 (median=46.5)
nition of NPC:11 one case was diagnosed as a nasopharyngeal Stage III 14, 3, 11, 45 (median=12.5) 74, 53, 10 (median=53.0)
chondroid cordoma, and another as a diffuse large non-
Stage IV 16, 5, 2, 48, 45, 49, 11, 26, 10, 7 32, 16, 31, 45, 50, 50
Hodgkin B-cell lymphoma. Three charts were not available
(median=13.5) (median=38.5)
for review; therefore, a total of 32 charts were reviewed.
Information collected from each patient’s chart and used All stages 21.0 42.0
in our analysis included: date of birth, age at diagnosis, sex,
birth place, occupation, smoking history, alcohol use, stage,
TNM diagnosis, date symptoms began, date of diagnosis,
date of biopsy, dates first seen by otolaryngologist, Medical Figure 1. Overall survival across all stages
Oncology and Radiation Oncology, date of first radiation for radiation alone vs chemoradiation
dose, dose of radiation, length of radiation treatment (days),
chemotherapy given post radiation (Y/N), dose reduction
of chemotherapy (Y/N), living at the time of chart review
(Y/N), date of death, metastases (Y/N), method of finding
metastases and local recurrence (Y/N).
All information was put into a standardized spreadsheet
and organized according to stage, treatment and outcome.
Outcome was separated into 12-month DFS, defined as the
percentage of patients who had no evidence of either local
recurrence or metastatic disease after 12 months from
diagnosis, and OS, defined as time (months) from date of
diagnosis to date of death from any cause.
Twelve-month disease-free survival (DFS) and overall
survival (OS) were recorded as simple calculations of the
median. To analyze OS stratified by treatment regime
(radiation vs chemoradiation), a Kaplan-Meier survival
curve was constructed, and a log-rank test was carried out Stage IV at diagnosis (Table 2).
to compare survival curves. Local recurrence was documented in 10 (31.3%) patients,
8 of whom were Stage III or IV at time of diagnosis.
Results Metastatic disease was also documented in 10 (31.3%) of the
Of the 32 patients included in this study, 22 (68.8%) were male, charts reviewed, with 9 of these patients being Stage III or
resulting in a male-to-female ratio of 2.2:1. The median age IV at diagnosis. A total of 22 (68.8%) patients were disease-
of patients at diagnosis was 56 years. Nearly two-thirds (23 free 12 months after diagnosis; 10 of these patients pre-
or 71.9%) reported having a smoking history, and 78.1% sented as Stage IV at diagnosis. As of September 2010,
claimed to be current consumers of alcohol (Table 1). 20 patients (62.5%) were alive. Median OS across all stages
Dividing the patients by histologic type, the vast majority was 34.3 months, with the shortest survival (14 months)
(25 or 78.1%) were WHO type I (squamous cell carcinoma). seen in Stage III patients (Tables 3 and 4).
Using the TNM classification system, 50.0% of patients were Comparing treatment regimens, 14 patients (43.8%)
received radiation therapy and 18 (56.3%)
received cisplatin-based chemotherapy in con-
Table 4. Patient outcomes, by stage at time of diagnosis junction with radiation. Treatments
Number of Local Metastasis 12-month Number OS
did not appear to differ according to stage,
patients recurrence DFS living (months) as all stages included patients treated with
radiation-only as well as patients treated with
Stage I 2 1 1 1 1 43.5
Stage II 7 1 0 7 7 50.0 Patients in the chemoradiation group lived
Stage III 7 4 4 4 3 14.0 longer compared to the radiation only group
(21 vs 42 months; Table 5). When comparing
Stage IV 16 4 5 10 9 25.0
treatment regimens across all stages, there was
All stages 32 10 (31.3%) 10 (31.3%) 22 (68.8%) 20 (62.5%) 34.3 no significant difference in the Kaplan-Meier
DFS=disease-free survival OS=overall survival survival curves (p=0.3533; Figure 1).
However, when the results were stratified by

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e-6 oe VOL. 10, No. 2, may 2011
stage at diagnosis, it appears that in earlier stages (I and II), that EGFR inhibitors, when combined with conventional
the radiation only groups survived longer, while in later stages chemotherapies, may offer improved outcomes.18 Unfortu-
(III and IV), OS was longer in the chemoradiation group. nately, the data regarding efficacy of EGFR inhibitors in the
metastatic setting seem to be limited.19 Additionally, although
Discussion studies have shown EBV latent membrane protein 1 (LMP1)
The objective of this retrospective review was to document to impact EGFR expression,20 the direct effects of this inter-
outcomes of NPC patients in NL and to draw a hypothesis action and how it affects the sensitivity of EBV-containing
on the best treatment options. In terms of epidemiology NPC cells to EGFR inhibitors need further study.
and patient characteristics, it was clear that our population
was similar to other NPC populations in the literature. The Conclusions
majority of patients were men in their late 50s with a history Our retrospective review found that the majority of patients
of smoking and alcohol use who were diagnosed with WHO with NPC in NL present at an advanced stage. As expected,
type I NPC.12 This enabled us to draw conclusions on the outcomes are worse for more advanced stages at presentation.
wider population of NPC patients. Also like the wider pop- This study also suggests that chemoradiation has the advan-
ulation, we had a large number of individuals presenting at tage of prolonging OS, especially in later-stage disease.
later stages (Stages III and IV). There have been hypotheses Further prospective study will be required to clearly define
regarding the reasons for late presentation, including vague optimal treatment.
symptoms, physical location in the skull and ease of metas-
tasis to cervical lymph nodes. Regardless of the cause, our Disclosure
study further demonstrates that earlier diagnosis is crucial, The authors report no conflict of interest relevant to this article.
since later stage at presentation leads to a greater likelihood
of metastasis and lower OS.
1. Statistics Canada. Canadian Cancer Statistics 2009. Retrieved from
Of interest is the marked difference in OS when adding 2. American Cancer Society. Cancer Statistics 2009. Retrieved from
chemotherapy to the treatment regimen for Stages III and IV 3. Cancer Research UK (2009). Statistics and Outlook for Nasopharyngeal Carcinoma.
patients. This is in concordance with a number of landmark Retrieved from
studies that show statistically significant OS benefits in both 4. Zheng YM, Tuppin P, Hubert A et al (1994). Environmental and dietary risk fac-
Stage III and Stage IV patients with cisplatin-based chemo- tors for nasopharyngeal carcinoma: a case-control study in Zangwu County,
Guangxi, China. Br J Cancer 1994;69:508-14.
radiation compared to radiotherapy alone.13,14 It should also 5. Yu M, Yuan JM. Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol
be noted that a large number of patients did not complete 2002;12:421-9.
the full intended dose of chemoradiation, due to side effects 6. Chang ET and Adami HO. The enigmatic epidemiology of nasopharyngeal carcinoma.
and/or advanced stage of disease. In fact, as a group, these Cancer Epidemiol Biomarkers Prev 2006;15:1765-77.
patients received two-thirds of the intended chemotherapy 7. Liu MT, Hsieh CY, Chang TH et al. Prognostic factors affecting the outcomes of
nasopharyngeal carcinoma. Jpn J Clin Oncol 2003;33:501-8.
during radiation; of those who were dose-reduced, all were
8. BC Cancer Agency. BCCA Protocol Summary for Treatment of Recurrent and
Stage III or Stage IV. Metastatic Nasopharyngeal Cancer using Cisplatin and Etoposide (2009).
Since this was a retrospective chart review, our study had Retrieved from
the limitations of availability of medical records, possible 9. National Cancer Institute. Nasopharyngeal Cancer Treatment (2009). Retrieved
selection bias and lack of randomization. Further, with our from
small sample size, any results could only serve to generate 10. Edge SB, Byrd DR, Compton CC et al, eds. AJCC Cancer Staging Manual, 7th ed.
New York: Springer, 2009.
hypotheses. Given the rarity of NPC, however, information 11. Mendenhall WM, Riggs CE Jr, Cassisi NJ. Treatment of head and neck cancers.
compiled from small chart reviews such as this will be neces- In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of
sary to provide the foundation for larger prospective studies. Oncology, 7th ed. Philadelphia: Lippincott Williams and Wilkins, 2005, pp. 662-732.
Although we did not specifically look at a subgroup analysis 12. Brennan B. Nasopharyngeal carcinoma. Orphanet J Rare Dis 2006;1:23.
of the Labrador Innu and Inuit population, this chart review 13. Al-Sarraf M, LeBlanc M, Giri PG et al. Chemoradiotherapy versus radiotherapy
in patients with advanced nasopharyngeal cancer: phase III randomized Inter-
did contain patients from this ethnicity. Native populations group study 0099. J Clin Oncol 1998;16:1310-7.
in Canada have comparable rates of NPC to those found in 14. Huncharek M, Kupelnick B. Combined chemoradiation versus radiation therapy
parts of Asia. In Nunavut, cancer of the nasopharynx alone in locally advanced nasopharyngeal carcinoma: results of a meta-analysis
accounted for 5.6% of reported cancers between 1992 and of 1,528 patients from six randomized trials. Am J Clin Onco 2002;25:219-22.
2001, and the rate of NPC was 14.6/100,000 for men and 15. Friborg JT, Melbye M. Cancer patterns in Inuit populations. Lancet Oncol 2008;
women combined.15 Further, it appears that of these Nunavut 16. Healey SM, Plaza D, Osborne G. A Ten Year Profile of Cancer in Nunavut:
patients, all were Inuit. It is thought that Epstein-Barr virus 1992–2001. Nunavut Department of Health and Social Services, 2003.
(EBV) may play a role in this population.16 Consequently, 17. Guigay J. Advances in nasopharyngeal carcinoma. Curr Opin Oncol 2008;20:264-9.
EBV testing may be beneficial in our local population in NL. 18. Hsu CH, Gao M, Chen CL et al. Inhibitors of epidermoid growth factor receptor
Our study adds to the mounting literature pointing to a suppress cell growth and enhance chemosensitivity of nasopharyngeal cancer
cells in vitro. Oncology 2005;68:538-47.
high rate of metastasis and local recurrence in patients with 19. Huang Y, Lin TY, Lu TX et al. Evaluation of epidermal growth factor receptor (EGFR)
advanced NPC. Treatment changes, such as possible new in nasopharyngeal carcinoma and lymph node metastases: Implications for
chemotherapeutic agents and different delivery schedules,17 EGFR targeted therapy. ASCO Annual Meeting Proceedings Part 1. J Clin Oncol
need to be considered. The use of targeted therapies such as 2007;25(18S):16510.
epidermal growth factor receptor (EGFR) inhibitors to treat 20. Kung CP, Raab-Traub N. Epstein-Barr virus latent membrane protein 1 induces
expression of the epidermal growth factor receptor through effects on Bcl-3
NPC is currently being investigated. Early studies have shown and STAT3. J Virol 2008:82:5486-93.

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