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Comparison trail of hyperfractionated radiotherapy vs conventional

radiotherapy in local control in advanced head and neck carcinoma


Taylor Evans
Summer RT program 2014
Introduction
In the United States, head and neck cancers account for roughly about 5% of all cancers,
squamous cell carcinomas count for more than 9 of 10 cancers of the oral cavity and
oropharynx.1 The American Cancer Society estimate about 37,000 individuals will be diagnosed
in 2014; approximately 7,300 of these individuals will die from these cancers. Men prevailing
over women, with possible rise in these cases have been linked with human papilloma
virus(HPV). The mean age of individuals are older than 55, although the linkage of HPV
infection has shown to arise in younger individuals. Surgery is the main treatment of choice;
although radiotherapy and chemotherapy are usually used in combination for treatment.2
Altered fractionation has made a significant approach with patients that have stage III and
IV local disease. One of the treatment arms for altered fractionation that is improving localregional control and overall survival at five years is hyperfractionation. Hyperfractionation uses
an increased number of fractions and total dose, a lower dose per fraction, and the same overall
treatment time (Eisele, 2010).3 Many randomized studies have been comparing conventional
fractionation, which consist of 1 fraction per day, 5 days a week, in a 4-8 week continuous
course, to hyperfractionization, usually consisting of 2 or more fractions a day, higher weekly
dose with treatment time shortened (Eisele, 2010).3 Within these studies the overall importance
is boosting the total dose administered by breaking up treatments into smaller fractions
(Godt,2014) .4 These different studies are trying to improve the probability of cure but also
reduce the feasibility of late complications compared to conventional radiotherapy. Within this
study I will be analyzing data from both male and female patients, older than 18 years of age,
with stage III and IV, proven squamous cell carcinoma, without evidence of distant metastases.
Patients with primary sites in the nasopharynx, hypopharynx, larynx, and oral cavity are eligible.
Previous studies have investigated treatments combining radiotherapy and chemotherapy,
exploring chemotherapeutic agents, reviewing pertinent literature and discussing optimal
management of previously untreated patients, survival improvement, and local-regional control
improvement. The aim of this study will analyze: local regional control, overall survival in

conventional radiotherapy and hyperfractionated radiotherapy groups, and to determine and


compare the acute and late side effects in each group.
Hypothesis
When hyperfractionation radiotherapy is used for local control in head and neck
patients with stage III or IV squamous cell carcinoma, outcomes of overall survival and late
side effects are more favorable compared to conventional radiotherapy. I believe
hyperfractionation is more beneficial with local control, although acute side effects will be more
dominate than compared to conventional because more fractions are give within a day. Thus,
patients will be receiving a higher weekly dose but benefiting with a shorter treatment time
period. Since treatment time will be reduced by a few weeks compared to conventional, more
acute side effects will be arising due to sublethal damaging of normal tissue from time between
fractions ( i.e 2 fractions per day). My critical prediction to my hypothesis is that local control in
head and neck patients receiving hyperfractionated radiotherapy will be best managed by
showing minimal to none long term effects, a decrease in second malignancies and improved
disease free survival at 5 years.
Literature Review
The Department of Radiation Oncology, University of Florida College of Medicine,
clinical review discussed the roles of altered fractionation and adjuvant chemotherapy combined
with radiotherapy treatment. Patients with stage III and IVA and/or B, whom were untreated,
were reviewed. The results depended on the schedule
Within the Lancet met-analysis, several trials were assed to determine if
hyperfractionated or accelerated radiotherapy improved survival. The methods used within these
trials included patients with non-metastatic head and neck squamous cell carcinoma, with
individual patient data being obtained. There were three separate trial groups: hyperfractionated,
accelerated, and total dose reduction acceleration. The main focus was the overall survival of
these trails being conducted. A 6 year median was used to follow up 15 randomized trails that
included 6515 patients. The main treatment focus site was oropharynx and larynx with stage III
and IV disease. Findings resulted in a 3.4% survival benefit with altered fractionation
radiotherapy at 5 years. Local regional control also had a favorable outcome at 6.5% at 5 years.
The conclusion was made that altered fractionation did indeed improve survival in head and neck

patients, which hyperfractionation having the greatest benefit when comparing all types of
altered radiotherapy. 4
The clinical investigation done though the Department of Radiation Oncology group in
Atlanta,GA tested if local control rates were improved through altered radiation fractionation
schemes compared to standard fractionation of 70Gy. 1076 patients diagnosed with stage III and
IV squamous cell carcinoma were randomized into 4 treatment arms ranging from 42 Gy to 81.6
GY in a 6-7 week span. The results found, within this investigation, was significantly different
between patients at 5 years in the hyperfractionation arms compared to the standard arms.
Hyperfractionation overall survival rate was improved within these 5 years. In conclusion, local
regional control was improved without increasing late toxicity using hyperfractionation. 5