the landmark veterans administration laryngeal cooperative study published in 1991 initiated the era of organ preservation .
today , many patients are advised to choose chemoradiation as their primary treatment for advanced oropharyngeal carcinomas ( stages iii 
, this typically results in high doses to the parotids , submandibular glands , and the mandible ( > 60  gy ) .
the resulting long - term complications of xerostomia and osteoradionecrosis are well known and negatively impact patients quality of life ( qol ) .
recent advances in computational power have allowed radiation therapy to be directed more specifically to the tumor bed .
the goal of using imrt is to limit the radiation dose to radiosensitive structures , such as the parotids and the mandible . within the literature ,
the literature has demonstrated that imrt protocols provide equivalent control rates and overall survival when compared to more traditional opposed port therapy .
however , it is unclear how the improved dosimetry impacts qol of long - term head and neck cancer survivors .
the protocols for this treatment are still being perfected , but the mainstay of chemotherapy for head and neck carcinomas involves 5-flurouracil , a nucleotide analog , and cisplatin  a dna chelating agent .
the side effects of these agents can be severe and include neutropenia , mucositis , renal toxicity , neuropathy , and hearing loss .
terrell et al .   demonstrated that the addition of chemotherapy to treatment negatively impacts qol of patients .
qol is a subjective perception by the patient that includes physical , emotional , and social well being .
it is well established that different subsites within the head and neck have different perceived qol following treatment ; patients with oropharyngeal carcinoma tend to report worse qol than do other head and neck cancer patients and have poorer functional outcomes [ 8 , 9 ] .
the need for gastrostomy and tracheostomy tubes , comorbid medical conditions , and need for a neck dissection all negatively affect qol outcomes .
a previous study demonstrated no difference in qol outcomes between patients who had undergone chemoradiation versus surgery and radiation for advanced oropharyngeal carcinoma . in the current
study a comparison between qol outcomes between patients who received chemotherapy and imrt ( cimrt ) versus standard chemoradiation with opposed port therapy ( crt ) was undertaken .
the hypothesis of this study is that cimrt patients experience improved qol compared to those undergoing crt .
patients were recruited from a tertiary referral center from a registry of patients who had undergone radiation therapy of all types from 2001 to 2006 .
patients had biopsy - proven squamous cell carcinoma of the oropharynx ( including tonsil , base of tongue , or pharynx ) .
these tumors were clinically staged as stage ii through iv based on criteria described by the american joint committee on cancer ( ajcc ) .
all patients involved in the study had undergone either primary concurrent chemoradiation ( crt ) or concurrent chemotherapy with imrt ( table  1 ) .
patients were excluded if they required surgical salvage after crt / cimrt or had metastatic disease at the time of diagnosis.table  1chemotherapy and radiation protocol for study participantsid no.tnmxrt typetotal xrt dosechemo1t4n1conventional7,020cisplatin / etoposide2t3n2bconventional7,0202 cisplatin/5fu3t3n2cconventional7,0002 cisplatin/5fu4t1n1conventional7,2001 cisplatin/5fu5t2n0conventional7,0002 carbo/5fu6t3n2conventional7,0202 cisplatin/5fu7t3n2bconventional5,4002 cisplatin/5fu8t1n2bconventional7,2002 cisplatin/5fu9t4n1conventional7,3802 cisplatin/5fu10t2n1conventional7,0002 cisplatin/5fu11t4n1conventional7,0202 cisplatin/5fu12t4n3conventional7,0202 cisplatin/5fu13t4n1conventional7,5603 cisplatin14t3n3conventionalnana15t4n0conventionalnana16t4n0conventional7,0202 cisplatin/5fu17t4n3imrt7,0002 cisplatin18t2n0imrt7,0002 cisplatin19t2n2aimrt7,0003 cisplatin/5fu20t1n2bimrt7,0002 cisplatin/5fu21t2n1imrt7,0002 cisplatin22t2n2imrt6,8003 cisplatin23t2n0imrt7,0002 cisplatin24t2n2bimrt7,0004 cisplatin25t4n3imrt7,0002 cisplatin26t3n2imrt6,800erbitux27t1n2bimrt7,0002 cisplatin28t3n2bimrt7,0002 cisplatin29t2n0imrt6,800none30t3n1imrt6,8002 cisplatinna records not available , 5fu 5 fluorouracil , carbo carboplatinpatient moved from area before finishing treatment chemotherapy and radiation protocol for study participants na records not available , 5fu 5 fluorouracil , carbo carboplatin patient moved from area before finishing treatment a total of 50 patients identified from institutional databases met eligibility requirements for the study .
all eligible patients were mailed copies of the university of washington quality of life questionnaire , version four ( uw - qolv4 ) .
patients voluntarily filled out the questionnaire at home and mailed their responses to the study organizers .
questionnaires were identified by a nondescript number , and data were entered into a confidential database . the uw - qolv4 instrument is scored on a scale of 0100 for the first and third segments .
the first section consists of 12 domains pertaining to the degree of qol in the categories of pain , appearance , activity , recreation , swallowing , chewing , speech , shoulder function , taste , saliva , mood , and anxiety . a score of 0 indicates very poor or no functional capacity with regard to that domain while a score of 100 indicates no disability in that domain .
the second segment of the questionnaire asks patients to choose three of the above domains that have been the most important to them in the past 7 days . in the final part of the instrument ,
patients are given three general questions comparing their ( 1 ) current health - related quality of life ( hr - qol ) to 1 month before developing cancer , ( 2 ) hr - qol during the past 7 days , and ( 3 ) overall qol during the past 7 days . the final segment is scored with 0 indicating very poor qol and 100 indicating outstanding qol , with a range of scores between .
statistical analysis of the responses was conducted using the wilcoxon rank sum test and the chi - square test .
results were adjusted to control for time from treatment to questionnaire and for tumor stage .
twenty - nine questionnaires were returned ( 58% return rate ) , with 16/30 patients in the crt cohort and 13/20 in the cimrt cohort .
eleven of 16 patients in the crt cohort and 9 of 14 patients in the cimrt group had stage iv tumors .
table  1 shows the various radiation doses and chemotherapy regimens for the responding patients .
the average time between the completion of treatment and questionnaire for the cimrt group was 13 months ( range 422 months ) while that for the crt group was 25 months ( range 453 months ) .
patients who received cimrt reported statistically significantly better qol with regard to appearance ( p  =  0.05 ) , chewing ( p  =  0.02 ) , and mood ( p  =  0.01 ) .
there was a trend toward significance in favor of cimrt with regard to anxiety ( p  =  0.08 ) , recreation ( p  =  0.07 ) , and activity ( p  =  0.07 ) .
no statistically significant difference was reported between the two cohorts with respect to saliva ( p  =  0.34 ) , pain ( p  =  0.47 ) , swallowing ( p  =  0.29 ) , speech ( p  =  0.50 ) , shoulder ( p  =  0.24 ) , and taste ( p  =  0.32 ) . with regard to overall qol and hr - qol
, there was no difference between the two groups ( p  =  0.31 and 0.09 , respectively ) .
however , when asked about qol compared to 1 month before the development of cancer , cimrt patients reported improved qol ( p  =  0.06 ) .
primary chemotherapy with radiation is a popular treatment option for patients with advanced oropharyngeal carcinoma .
recent advances have allowed for conformal radiation treatment strategies in order to minimize complications in radiosensitive structures .
qol in long - term survivors is an important outcome measure and is currently an active area of research . in this study ,
qol outcomes were compared in a cohort study between traditional opposed port radiotherapy and imrt ; both groups received concomitant chemotherapy .
overall qol was not different in the cimrt patients ; however , several domains did demonstrate improved qol as measured by the uw - qolv4 .
no difference was detected for all other domains , including saliva , taste , and swallowing .
specific evaluation of the global and hr - qol in patients treated for oropharyngeal carcinoma with imrt is limited .
the majority of studies available evaluate xerostomia and xerostomia - related qol [ 11 , 12 ] .
of the studies that evaluate global qol , it has been demonstrated that imrt patients experience improved qol [ 13 , 14 ] .
yao et al .   recently published the only study focused on oropharyngeal cancer survivors specifically .
they evaluated 56 patients with the head and neck cancer inventory which measures hr - qol and questions about their diet .
they found that eating and dysphagia scores were significantly improved in the imrt group of patients .
other domains demonstrated improved qol scores for imrt patients but did not reach statistical significance .
furthermore , 1 year after treatment the imrt patients scores continued to improve while the crt patients scores had reached a plateau . in the current study ,
a different head and neck specific instrument was used , specifically the uw - qolv4 ; thus it is somewhat difficult to compare the data .
however , it is apparent there were differences between the findings of the iowa group and our cohort . in the present study , only 3 of 12 domains demonstrated significance although several domains approached significance .
specifically , patients did not report improved saliva or swallowing in our study while yao et al .   did report improvement for these domains .
other studies in the literature have looked primarily at either xerostomia - related qol or dysphagia - related qol .
studied the dosimetry to the constrictor muscles in oropharyngeal carcinoma patients and determined that higher doses delivered to these muscles resulted in higher rates of severe dysphagia and gastrostomy dependence .
their study is somewhat difficult to interpret because not all patients received chemotherapy , which may lead to increased scarring in the pharyngeal musculature . in our study , patients received relatively uniform chemotherapy regimens and similar dosimetry to tumor .
the patients in our cohorts did not report improved swallowing or saliva , but cimrt patients did report better chewing .
the noted improvement in chewing may be explained by the sparing of the intrinsic musculature of the tongue and other oral structures with imrt .
the ability to manipulate the bolus within the oral cavity is an integral part of the oral phase of chewing .
the results for saliva are somewhat surprising based on the radiation protocol in effect at our institution .
all patients with oropharyngeal primary tumors who undergo imrt receive 70  gy to the gross tumor .
sites within the oropharynx or neck with likely microscopic disease receive 63  gy and sites with potential or remote disease receive 56  gy .
the parotid glands are carefully identified and mapped so that 50% of each gland received only 20  gy . the rest of the gland receives doses from 56 to 70  gy ( see fig .  1 ) .
with approximately half of the gland spared from high dose radiation , recovery of salivary function is expected within several months after the completion of treatment .
conversely , patients treated with conventional ( opposed port ) radiation do not have sparing of the parotid glands . for treatment of the oropharynx ,
minimal salivary function is expected to return in these patients . given the differences between the radiation protocols , the lack of difference regarding salivary qol is surprising .
perhaps those undergoing imrt have decreased perception of salivary flow when compared to pre - therapy flow rates and thus report decreased salivary qol.fig .  1radiation planning diagram for t4 carcinoma of the right tonsil .
the primary tumor volume receives 70  gy ( marked t and shaded in red ) .
the radiation plan is designed to spare 50% of each parotid gland ( blue - shaded area identified by the arrowhead ) .
the dose distribution lines show rapid falloff in the radiation dose between the tumor and the majority of the parotid gland
. a small amount of the gland receives high dose radiation where the tumor approaches the gland radiation planning diagram for t4 carcinoma of the right tonsil .
the primary tumor volume receives 70  gy ( marked t and shaded in red ) .
the radiation plan is designed to spare 50% of each parotid gland ( blue - shaded area identified by the arrowhead ) .
the dose distribution lines show rapid falloff in the radiation dose between the tumor and the majority of the parotid gland .
a small amount of the gland receives high dose radiation where the tumor approaches the gland patients receiving cimrt did report significantly better mood and appearance than their crt counterparts .
perhaps there is less  woody induration  in imrt patients , which results in a more supple appearance to the neck contour and hence an improved perception of appearance . the results with regard to mood were unexpected and can not be explained by a difference either in final xrt dose or in chemotherapy regimens , as these were similar between the groups .
these results are inherently biased and dependent on the patient s expectations of their treatment and its outcomes . perhaps , the cimrt patients reported better mood because they expected to feel better after treatment .
other differences in the perceived qol of these patients may be elucidated with a different qol instrument .
there are a number of head and neck specific questionnaires available which have been validated in the literature including the hr - qol , eortc - c30 with the eortc - h&n35 , and uw - qol . a recent review by tschiesner et al .   compared these instruments using the international classification of function , disability , and health ( icf ) schema .
using this schema , the content of the instruments can be more easily compared as the instrument content was correlated with specific icf concepts .
the eortc questionnaires cover a broader range of icf categories when compared to the uw - qol .
the eortc instrument includes questions regarding memory and attention functions ; sexual functions ; respiratory functions ; a variety of activities of daily living such as toileting and dressing ; and smell .
this instrument is used widely in europe but less commonly in the united states . however , both instruments have approximately 70% of their content that can be correlated to an icf category ; the eortc instrument covers 43 categories while the uw - qol covers 23 categories .
two of the major benefits of the uw - qol , and the reason it was chosen for this study , are its broad range of questions and the relative ease of completion . in order to encourage participation in the veteran population from which this cohort was drawn , an instrument which could be completed quickly but covered a broad range of topics was required .
the uw - qol can be completed in a quarter of the time needed to complete the eortc instruments .
the differences between the two radiation groups may be helpful when deciding which radiation modality to use for specific patients .
those patients with comorbid conditions report having significantly worse qol prior to beginning therapy than those without these conditions . in these patients , all other factors being equal
, cimrt may be a better option to try to minimize the negative impact of therapy on their already diminished qol .
other treatment options for advanced oropharyngeal carcinoma include surgery with adjuvant radiation ( or chemoradiation ) .
surgical therapy is associated with late toxicity , including scarring , fibrosis , laryngeal , and esophageal stenoses , all of which also affect qol for head and neck cancer patients .
as both appearance and chewing can be significantly impacted by surgery , it is possible that patients who undergo primary cimrt may have improved qol compared with patients who undergo surgery and radiation .
although there were no differences noted between the two chemoradiation groups in the aforementioned study , the impact of cimrt on qol when compared to surgery and radiation is yet to be explored .
while none of the patients in this study received induction chemotherapy , it is known that chemotherapy , in general , negatively impacts on qol .
how the timing of chemotherapy , induction , or concomitant , impacts qol has not been explored .
it seems likely that although early toxicity of therapy may be diminished in those patients undergoing induction chemotherapy , the long - term effects on qol would be similar to those receiving concomitant chemoradiation .
one limitation to this study was that our sample size was small , and there may not have been sufficient power to find significant differences between the two groups . a larger number of patients may demonstrate subtle differences between the groups and may result in statistically significant differences for anxiety , recreation , and activity .
an ideal study would be a prospective longitudinal one involving a larger number of patients , and in future such studies are planned .
however , we believe that this current study is a valuable pilot study which yields important information about what oropharyngeal cancer patients should expect from crt and cimrt , especially when discussing the benefits of a given treatment .
it is important not to overstate the benefits of that treatment and ensure that patients have realistic expectations for their post treatment qol .
patients who receive chemotherapy and imrt do have improvement in certain domains of qol , specifically appearance , mood , and chewing . however , with regard to overall qol , cimrt and crt patients have similar perceptions of qol .
surprisingly , in our study cimrt patients did not report better saliva or swallowing when compared to crt patients . although studies in the literature demonstrate improved salivary flow rates with parotid sparing radiation regimens , this does not appear to have improved the patients perceptions of dry mouth following treatment .
 this study is based on the context that many patients with advanced oropharyngeal carcinoma are being treated with primary chemoradiation . 
 the aims of this study are to identify differences in quality of life ( qol ) between patients with advanced oropharyngeal cancer following traditional chemoradiation versus chemotherapy with intensity - modulated radiation therapy ( cimrt ) . 
 this research is designed on a cohort study from an academic tertiary referral center . 
 fifty patients were identified from an institutional database of patients who had undergone primary chemotherapy and radiation ( traditional or imrt ) for advanced oropharyngeal carcinoma . 
 patients responded via mail using the university of washington quality of life instrument version 4 . 
 statistical analysis of data was performed using chi - square and wilcoxon tests . 
 the results comprise the responses of 17 crt ( 57% ) and 14 cimrt ( 70% ) patients . 
 the patients completed the survey between 9 and 44 months following end of treatment . when adjusted for tumor stage and time since treatment , cimrt patients reported improved appearance ( p  =  0.05 ) , chewing ( p  =  0.02 ) , and mood ( p  =  0.01 ) 
 . there was a trend toward significance for improved activity ( p  =  0.07 ) , recreation ( p  =  0.07 ) , and anxiety ( p  =  0.08 ) . 
 there were no differences between the two groups for saliva , taste , shoulder function , speech , and swallowing . 
 but there was a trend for significance for improved overall qol in patients who had undergone cimrt ( p  =  0.06 ) . in conclusion , 
 cimrt results in improved qol for some domains but surprisingly not for swallowing or saliva . 
 patients undergoing cimrt also report slightly better qol overall when compared to patients receiving more traditional forms of radiation therapy . 