1. Running head: SCCHN & WEIGHT 1
Impact of Squamous Cell Carcinoma of the Head/Neck (SCCHN) on Weight Status
Abigail Smith
University of Kentucky

2. SCCHN & WEIGHT 2
Abstract
The purpose was to examine the impact of diagnosis and treatment of squamous cell
carcinoma of the head/neck (SCCHN) on weight status over a 5-week period. A sample of
25 SCCHN patients treated with radiation therapy for a minimum of 5 weeks was
retrospectively analyzed. Comparison of the mean weight change over the 5-week period
did not yield statistically significant results (p=0.72). The average weight loss over 5 weeks
was 3.12% (2.38 kg). Multiple linear regression examining the association between
explanatory variables – age, gender, tumor site – and the response variable – percent
weight change – explained 13.44% of weight change in this population (R2 =0.13442). Each
additional year of age was associated with a 0.087% weight loss (p=0.13). Men were
associated with 2.19% less weight loss over 5 weeks than women (p=0.38). Oral tumor site
was associated with a 3.05% greater weight loss over 5 weeks when compared to other
tumor H/N tumor sites (p=0.058). Though results did not reach statistical significance, this
study suggests substantial clinical implications. Data regarding the anticipated average
weight loss and risk factors for increased weight loss in HNC patients could be used to
guide healthcare professionals and caregivers in choosing an optimal prophylactic
nutrition strategy.

3. SCCHN & WEIGHT 3
Impact of Squamous Cell Carcinoma of the Head/Neck (SCCHN) on Weight Status
Review of Literature
Introduction
Cancer is the second leading cause of death in the United States; 1,630 people die of
cancer every day(American Cancer Society, 2016). In 2016, there is projected to be an
estimated 1,685,210 new cancer cases and 595,690 deaths from cancer in the United
States. Of these, an estimated 48,330 new cases and 9,570 deaths will be comprised of
head and neck cancer (HNC) diagnoses (Siegel, Miller, & Jemal, 2016). The National Cancer
Institute cited a significant increase in head and neck cancer cases from 1983-2002
(National Cancer Institute, 2013). From 2003-2012, the instance of head and neck cancer,
specifically oral cavity and pharynx (throat) increased by 1.3% per year, or 11.7% over 9
years, in white males (American Cancer Society, 2016). Squamous cell carcinoma accounts
for 40% of HNC cases (Mignogna, Fedele, & Lo Russo, 2004).
HNC is typically detected at a more advanced stage, which leads to poorer outcomes
(Mignogna et al., 2004). Survival rate varies substantially by stage at diagnosis as well as
the site of the tumor. Lip tumor is associated with a 90% survival rate, salivary gland 73%,
floor of mouth 51%, and hypopharynx 32% (American Cancer Society, 2016).
Treatment
HNC causes noticeable symptoms that impair normal function including dysphagia,
aspiration, vocal changes, and pain (List & Bilir, 2004). About 50% of patients express pain
related to their HNC diagnosis prior to any treatment. However, the treatment of HNC
brings about even more side effects than the cancer itself. Approximately 81% of patients
express pain during treatment. A number of treatment regimens are used to irradiate HNC,

4. SCCHN & WEIGHT 4
including surgery, radiation therapy, chemotherapy, and a combination thereof. The most
common treatment complications are mucositis, infection, salivary gland dysfunction, taste
dysfunction, and pain, which lead to secondary complications such as dehydration,
dysgeusia, and malnutrition (National Cancer Institute, 2016).
The most common treatment for HNC is radiation therapy (Department of Health
and Human Services, 2015). Radiation often leads to complications such as xerostemia
(>66% of patients), difficulty eating/swallowing (~35-68%), sticky saliva (~33%), pain
(~15-30%), and change in appearance (~20-25%), among others (List & Bilir, 2004).
Difficulty chewing and swallow dysfunction are the most common complications associated
with radiation therapy for treatment of SCCHN, occurring in at least 2/3 of patients (Silver
et al., 2010). Significant oral and nutritional problems occur in up to 80% of patients
treated with radiation therapy (List & Bilir, 2004).
Weight Loss
Studies have documented the weight loss associated with treatment of HNC. Platek
et al. (2013) retrospectively compared the weight status and loco-regional SCCHN
progression of two cohorts treated with concurrent chemoradiation therapy (CCRT). Both
cohorts experienced an overall average weight loss of 9% over the 7-week treatment
period. This weight loss was attributed to dysphagia, xerostemia, radiation-induced
mucositis, and other CCRT-related toxicities. There were no significant differences between
the two cohorts despite the provision of nutritional intervention to the treatment cohort
(Platek et al., 2013).
Silver et al. (2010) observed SCCHN patients throughout treatment with CCRT and
post-treatment follow-ups to identify predictors of functional decline. Patients experienced

5. SCCHN & WEIGHT 5
approximately 12% loss of total body mass averaging 13.1 ± 11.2 kg over a 6-month
period. Significantly large losses in mid-arm, mid-calf, and waist circumference were also
noted. The study identified four main factors associated with functional decline: difficulty
chewing and/or swallowing, weight loss, fatigue, and perceived stress (Silver et al., 2010).
A comprehensive literature search identified numerous risk factors for weight loss
associated with HNC and its treatment. The top three risk factors identified by this study
were advanced tumor stage, higher BMI before treatment, and the use of CCRT. Advanced
tumor stage was found to be an independent risk factor for weight loss. Although not an
independent risk factor, patients with an overweight/obese BMI classification experienced
significantly greater weight loss than patients with a normal or underweight BMI (Zhao,
Zheng, Li, Zhang, Zhao, & Jiang, 2015).
Importance of Nutrition
Malnutrition occurs in approximately 80% of cancer patients at some time during
treatment. Poor nutritional status during treatment is associated with increased morbidity
and mortality. Further, markers of malnutrition including weight loss and low muscle mass
index are predictive of patient survival. Weight loss of as little as 5% decreases survival
rate (Oncology Nutrition, 2014). Weight loss exceeding 5% within 3-12 months combined
with symtpoms including fatigue, loss of skeletal muscle, and biochemical abnormalities is
defined as cachexia. Cancer cachexia is the third most frequent subtype based on
population prevalence; 60-80% of patients with advanced cancer have cachexia. Within
the cancer population, more than 30% of patients die due to cachexia and 50% of patients
die with cachexia present. There is an 80% mortality rate of patients with cancer cachexia
(Von Haehling & Anker, 2010).

6. SCCHN & WEIGHT 6
Malnutrition also restricts patient ability to proceed with cancer treatment and
reduces overall quality of life. Continued malnutrition following completion of cancer
treatment increases the risk of cancer recurrence (Oncology Nutrition, 2014).
Cancer patients have increased energy and protein requirements due to a higher
resting metabolic rate as a result of disease state and/or treatment. Increasing energy and
protein intake can help prevent weight loss and loss of muscle mass (Gullett, Mazurak,
Hebbar, & Ziegler, 2011). However, disease and treatment related complications
frequently prevent adequate oral intake (List & Bilir, 2004). For these reasons,
multidisciplinary approaches to cancer treatment include registered dietitians to minimize
weight loss and educate patients on the importance of good nutrition throughout treatment
(Department of Health and Human Services, 2015).
Conclusions
HNC alone, and in conjunction with its treatment complications, causes significant
nutritional problems including severe weight loss. Malnutrition and weight loss are
associated with a decrease in patient survival rate. Studies have identified predictors of
increased weight loss, however, no nutritional interventions have shown a statistically
significant difference in preventing weight loss. With the continuing increase in new cases
and deaths from HNC, it is clear that HNC is a rising concern that warrants additional
research. Given the proven importance of nutrition during cancer treatment and the
documented weight loss HNC patients experience, efforts should be focused on preventing
malnutrition and weight loss within this population.

7. SCCHN & WEIGHT 7
Hypothesis
Individuals diagnosed with and treated for squamous cell carcinoma of the head/neck
(SCCHN) will experience significant weight loss within the first 5 weeks of treatment with
radiation therapy.
SMART Objectives
Measure the average weight change of individuals treated for squamous cell carcinoma of the
head/neck within the first 5 weeks of treatment with radiation therapy. Identify risk factors for
increased weight loss in individuals treated for squamous cell carcinoma of the head/neck during
treatment with radiation therapy.
Methodology
Design and Setting
This retrospective observational study of SCCHN patients was reviewed and approved by
the Psychology-Oncology Department at the University of Kentucky Markey Cancer Center in
Lexington, Kentucky. Patients diagnosed with an oral or throat squamous cell carcinoma tumor
and treated with radiation therapy for a minimum of 5 weeks at the time of data collection were
eligible for this review.
Outcomes Collected
Retrospective patient information was collected from the paper medical records available
in Radiation Medicine at the UK Markey Cancer Center which included the following: age at
diagnosis, gender, tumor site, tumor stage, height and weight, and the type of tube feeding if
applicable. Not all patient medical records included complete information. Of the 25 records
reviewed, 5 did not contain tumor stage and 7 did not include height. Measurements of body
weight were collected bi-weekly throughout the 5-week treatment observation period.

8. SCCHN & WEIGHT 8
Weight change over the 5-week period was calculated by subtracting starting weight from
ending weight, measured in kilograms. Percent weight change was calculated by dividing weight
change in kilograms by starting weight in kilograms and multiplying by 100. Body mass index
(BMI) was calculated as weight in kilograms divided by height in meters squared using both
starting weight and ending weight. BMI change over the 5-week period was calculated by
subtracting starting BMI from ending BMI.
Statistical Analysis
The statistical package for Excel 2011 for Mac StatPlus: Mac LE (Build 6.0.3) was used
for all statistical analyses. The t-test assuming unequal variances (heteroscedastic) for comparing
means was used to examine the statistical significance of the observed weight change. Multiple
linear regression was used to examine the strength of relationship between predictors – age,
gender, tumor site – and the response variable – percent weight change. A p value of <0.05 was
considered statistically significant.
Results
Twenty-five SCCHN patients treated with radiation therapy at the UK Markey
Cancer Center were examined. An examination of weight change over the 5-week
treatment period did not yield statistically significant results. The average starting weight
was 82.54 kg. The average ending weight was 80.16 kg. The average weight change in the
5-week period was a loss of 2.38 kg. The average percent weight loss was 3.12%. Figure 1
provides a comparison of the average starting weight and average ending weight. The
sample means t-test for comparing the mean starting and ending weight (kg) resulted in a p
value of 0.72.

9. SCCHN & WEIGHT 9
Figure 1: Comparison of average starting and ending weights
Table 1 provides descriptive characteristics for the population studied. The median
age of the patient population was 58.52 years. Of the 25 patients, 12 had a tube placed for
feeding, the most common type being a PEG tube.
Tumor site was refined for analysis and classified as “oral” if the tumor was located in the
oral cavity or “other” if it was otherwise located. Within this patient population, 32%
(8/25) of tumors were orally located.
Table 1: Population descriptive characteristics
Characteristics, n=25
Average age in years at diagnosis 58.52
Gender, male/female 23/2
Tumor site, oral/other 8/17
Average starting weight in kg 82.54
Average ending weight in kg 80.16
Tube feeding, yes/no 12/13
Within the population for which tumor staging was available, tumor progression
was classified as advanced if the TNM staging included an “N” of 1 or greater, indicating the
82.54
80.16
78.5
79
79.5
80
80.5
81
81.5
82
82.5
83
Starting Weight Ending Weight
Weight(kg)

10. SCCHN & WEIGHT 10
presence of lymph involvement. Of the 20 patients with staging information available, 60%
(12/20) had advanced tumor progression.
Of the population for which BMI information was available (n=18), 6% were
underweight (BMI <18.5) before treatment, 50% were normal weight (BMI 18.5-24.5), and
44% were overweight or obese (BMI >25). Median starting BMI was 23.8.
Multiple linear regression examined the association between explanatory variables
– age, gender, tumor site – and the response variable – percent weight change. Table 2
provides the results of the linear regression by variable. The linear regression model run in
this study using the aforementioned explanatory variables explained 13.44% of weight
change in this population (R2 =0.13442). Within the regression, each additional year of age
was associated with a 0.087% weight loss. Though this was not statistically significant
(p=0.13). Men were associated with 2.19% less weight loss over 5 weeks than women
though this was also not statistically significant (p= 0.38). Oral tumor site was associated
with a 3.05% greater weight loss over 5 weeks when compared to other tumor head and
neck tumor sites (p=0.058).
Table 2: Multiple linear regression by variable
Variables Effect on % Weight Change p value
Age 0.087% more weight loss in 5
weeks per year of age
0.13
Gender 2.19% less weight loss in 5
weeks associated with males
compared to females
0.38
Tumor Site 3.05% more weight loss in 5
weeks associated with oral
tumor compared to other H/N
tumor sites
0.058

11. SCCHN & WEIGHT 11
Discussion
Statistical Analysis
In this sample of patients treated with radiation therapy for SCCHN, weight change
over the 5-week week period was not statistically significant. However, the mean weight
loss of a 3.12% has clinical significance. Cachexia is defined as weight loss exceeding 5%
within 3-12 months (Von Haehling & Anker, 2010). Given the shorter time period studied
and the location early within the radiation cycle, the observed weight change is indicative
of likely cachexia status. More than 30% of cancer patients die due to cachexia and 50% of
patients die with cachexia present (Von Haehling & Anker, 2010). Additionally, cachexia
and malnutrition limit patient ability to proceed with cancer treatment and reduce overall
quality of life. Continued malnutrition and weight loss following treatment increase the risk
of cancer recurrence (Oncology Nutrition, 2014).
Multiple linear regression examined the association between explanatory variables
– age, gender, tumor site – and the response variable – percent weight change. In this
analysis, increased age was associated with an increased weight loss. Each additional year
of age was associated with an additional 0.087% weight loss. However, this was not
statistically significant (p=0.13). This association may be due to a number of reasons
related to advanced age including food insecurity and diminished health status
independent of cancerous state.
Within the regression model, there were gender differences in weight change over
the observed 5-week period. Men were associated with 2.19% less weight loss over a 5-
week period than women, though this was also not statistically significant (p= 0.38). In
other words, women were associated with a 2.19% greater weight loss than men in 5

12. SCCHN & WEIGHT 12
weeks. Zhao et al. (2015) identified female sex as a risk factor for increased weight loss in
HNC patients (Zhao et al., 2015).
In this analysis, oral tumor site was associated with a 3.05% greater weight loss
over 5 weeks as compared to other head and neck tumor sites (p=0.058). Although this
association did not reach statistical significance (p<0.05), it came very close. This finding is
consistent with research, which named oral cavity tumor site as a risk factor for increased
weight loss in HNC patients (Zhao et al., 2015).
An earlier regression model also examined the presence/absence of tube feeding,
tumor progression, and starting BMI as explanatory variables associated with percent
weight change. However, when these variables were included in the analysis, p values
increased, meaning they were farther from reaching statistical significance.
Limitations
The small sample size (n=25) is largely responsible for the high p values associated
with analyses in this study. There was a short period allotted for data collection (7 weeks)
and limited access to medical records, which reduced the quantity of data collected. Unless
H0 is true, a larger sample size is associated with a smaller p value because uncertainty
decreases with an increased sample size.
Some patients were still receiving treatment when data was collected and therefore,
their medical records do not show the full timeline of their treatment from start to finish.
These incomplete records were still used in this analysis due to the difficulty of obtaining
data. According to Silver et al. (2010), the most significant weight loss occurs beginning
around weeks 3-5 of treatment and weight loss continues for around 6 months following
treatment (Silver et al., 2010). Due to the availability of patient records, only the first 5

13. SCCHN & WEIGHT 13
weeks of treatment were examined. This limitation further explains why the observed
weight loss did not reach statistical significance.
Incomplete patient records caused other errors in this study. Within patient medical
records, weight measurement was not always labeled as “pounds” or “kilograms” so the
researcher’s best guess was used. Height was not always recorded. This prevented the
calculation of BMI. Zhao et al. (2015) identified a higher pre-treatment BMI as a strong
predictor of increased weight loss in HNC patients (Zhao et al., & Jiang, 2015). However,
when this variable was included in the regression model, n was decreased to 18 due to the
lack of available height – and subsequently BMI – information for the total population of
n=25. As previously explained, this decreased n resulted in increased p values. Similarly,
tumor staging was not always recorded which prevented the determination of tumor
progression. Zhao et al. (2015) also identified advanced tumor stage as an independent
predictor of increased weight loss in HNC patients (Zhao et al., 2015). When this variable
was included in the regression model, n was decreased to 20 due to lack of available
staging data for the total population of n=25 which consequently decreased the resulting p
values. Finally, treatment details including duration, strength, target area, and concurrent
therapies (i.e. surgery and chemotherapy) were unavailable in the paper medical records
obtained from the Radiation Medicine Department. Zhao et al. (2015) identified a higher
radiation dose, presence of radiation on neck nodes, and accelerated radiation treatment
schedule as risk factors for increased weight loss in HNC patients (Zhao et al., 2015). Platek
et al. (2013) found that a decreased treatment time was associated with a decrease in
weight loss (Platek et al., 2013). Since this treatment information was not available, it was
not included the analyses.

14. SCCHN & WEIGHT 14
Zhao et al. (2015) named absence of tube feeding at the start of radiation therapy as
a risk factor for increased weight loss in HNC patients (Zhao et al., 2015). In this study, the
presence or absence of tube feeding was noted when included in patient medical records.
However, due to the retrospective observational nature of this study, it was impossible to
determine if tube feeding was used during treatment period examined (first 5 weeks) and if
patients utilized tube feeding at all (noncompliance issues). Therefore, the
presence/absence of tube feeding was not included in the regression analysis, although
there is reason to believe the presence of tube feeding is associated with decreased weight
loss.
Future Research
Despite the lack of statistical significance resulting from this study, these findings
should encourage additional research in this area, potentially using a similar model to
explore these results more thoroughly. Future studies should examine a larger sample size.
Research design may be altered to follow patients as they are receiving treatment and for
approximately one year post-treatment to monitor ongoing weight changes, cancer
recurrence, and death. This would also allow researchers to more closely monitor the use
of tube feeding for a more accurate analysis of this variable. Research in a setting with
more support from oncology doctors, nurses, and dietitians would also be beneficial
because records would contain more complete information (i.e. height, tumor staging, etc.)
needed for a more complete analysis.
Clinical Implications
The results of both this study and proposed future studies could have substantial
clinical implications. Information regarding the anticipated average weight loss and risk

15. SCCHN & WEIGHT 15
factors for increased weight loss in HNC patients could be used to guide healthcare
professionals and caregivers in choosing an optimal prophylactic nutrition strategy based
on the presence or absence of these risk factors. Earlier and more effective nutrition
interventions may lessen the effects of cancer cachexia or prevent it altogether, thereby
improving prognosis and increasing survival rate (Oncology Nutrition, 2014).

16. SCCHN & WEIGHT 16
References
American Cancer Society. (2016). Cancer Facts & Figures 2016. Retrieved April 15, 2016,
from
http://www.cancer.org/research/cancerfactsstatistics/cancerfactsfigures2016/
Department of Health and Human Services, State Government of Victoria, Australia (2015).
Patient management framework head and neck tumour stream… Retrieved April 11,
2016, from
https://www2.health.vic.gov.au/about/publications/policiesandguidelines/Head%
20and%20neck%20tumour%20stream%20larynx%20pharynx%20and%20oral%2
0cancer
Gullett, N. P., Mazurak, V., Hebbar, G., & Ziegler, T. R. (2011). Nutritional interventions for
cancer-induced cachexia. Current Problems in Cancer, 35(2), 58–90.
doi.org/10.1016/j.currproblcancer.2011.01.001
List, M. A., & Bilir, S. P. (2004). Functional outcomes in head and neck cancer. Head and
Neck Cancer, 14(2), 178-189. doi:10.1053/j.semradonc.2003.12.008
Mignogna, M. D., Fedele, S., & Lo Russo, L. (2004). The World Cancer Report and the burden
of oral cancer. European Journal of Cancer Prevention: The Official Journal of the
European Cancer Prevention Organisation (ECP), 13(2), 139-142. Retrieved April 15,
2016.
National Cancer Institute. (2013). Worldwide trends show oropharyngeal cancer rates
increasing. Retrieved April 20, 2016, from http://www.cancer.gov/news-
events/press-releases/2013/HPVOropharynxWorldwideTrend

17. SCCHN & WEIGHT 17
National Cancer Institute. (2016). Oral Complications of chemotherapy and head/neck
radiation. Retrieved April 20, 2016, from http://www.cancer.gov/about-
cancer/treatment/side-effects/mouth-throat/oral-complications-hp-pdq
Oncology Nutrition. (2014). A Dietetic Practice Group of the Academy of Nutrition and
Dietetics. Assessing relationships between access to standardized
nutritional care and health outcomes and cost-effectiveness of care in
outpatient cancer centers. Accessed January 26, 2016: http://dpg-
storage.s3.amazonaws.com/ondpg/documents/36c67c706facc95/IOM_ONDPG_Wo
rkshop_2014.pdf.
Platek, M. E., Myrick, E., Mccloskey, S. A., Gupta, V., Reid, M. E., Wilding, G. E., . . . Singh, A. K.
(2013). Pretreatment weight status and weight loss among head and neck cancer
patients receiving definitive concurrent chemoradiation therapy: Implications for
nutrition integrated treatment pathways. Supportive Care in Cancer, 21(10), 2825-
2833. doi:10.1007/s00520-013-1861-0
Siegel, R. L., Miller, K. D., & Jemal, A. (2016). Cancer statistics, 2016. CA: A Cancer Journal for
Clinicians, 66(1), 7-30. doi:10.3322/caac.21332
Silver, H. J., Guimaraes, C. D., Pedruzzi, P., Badia, M., Carvalho, A. S., Oliveira, B. V., . . .
Pietrobon, R. (2010). Predictors of functional decline in locally advanced head and
neck cancer patients from South Brazil. Head & Neck, 32(9), 1217-1225.
doi:10.1002/hed.21322
Von Haehling, S., & Anker, S. D. (2010). Cachexia as a major underestimated and unmet
medical need: facts and numbers. Journal of Cachexia, Sarcopenia and Muscle, 1(1),
1–5. http://doi.org/10.1007/s13539-010-0002-6

18. SCCHN & WEIGHT 18
Zhao, J., Zheng, H., Li, L., Zhang, L., Zhao, Y., & Jiang, N. (2015). Predictors for weight loss in
head and neck cancer patients undergoing radiotherapy. Cancer Nursing, 38(6).
doi:10.1097/ncc.0000000000000231