Tissue/DoseCompensationtoReduceToxicity ... · with TDC had a smaller radiation dose gradient (Fig. 1) across the treatment volume (Plane 1 maxi-mum dose P 0.01 and Plane 2 maximum

Tissue/Dose Compensation to Reduce Toxicityfrom Combined Radiation and Chemotherapy

for Advanced Head and Neck Cancers

Bharat B. Mittal, M.D.,1* Alan Kepka, Ph.D.,1 Arul Mahadevan, M.D.,1

Merrill Kies, M.D.,2 Harold Pelzer, M.D.,3 Marcy A. List, Ph.D.,4

Alfred Rademaker, Ph.D.,5 and Jeri Logemann, Ph.D.61Department of Radiology, Section of Radiation Oncology,

Northwestern University, Chicago, Illinois2Department of Thoracic/Head and Neck Medical Oncology,

M.D. Anderson Cancer Center, Houston, Texas3Department of Otolaryngology and Head and Neck Surgery,

Northwestern University, Chicago, Illinois4University of Chicago Cancer Research Center, Chicago, Illinois

5Biostatistics Core Facility, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois6Department of Communication Sciences and Disorders,

Northwestern University, Evanston, Illinois

SUMMARY This study was undertaken to quantify the reduction in normal tissuecomplications resulting from the aggressive management of advanced head and neckcancers (AHNCs) utilizing tissue/dose compensation (TDC). Thirty-nine patients withAHNC were treated on an intensive chemotherapy � radiation regimen. Eighteen of 39patients were treated using TDC; the remaining 21 patients were radiated without TDC(NTDC). Acute and chronic toxicities, swallowing, speech function, and quality of lifewere assessed. The TDC group had a smaller radiation dose gradient across the entiretreatment volume. Unscheduled treatment breaks were required in 11% of TDC patientsas compared with 43% of the NTDC group (P � 0.04). The TDC group had fewer Grade3 or 4 acute and chronic toxicities and lower SOMA scores. At 3 months posttreatment,patients in the TDC group had better oral intake, lower pharyngeal residue, and betteroropharyngeal swallowing efficiency and were able to swallow more bolus types. Patientsin the TDC group also had better articulation. Use of TDC resulted in reduced treatment-related interruptions, decreased acute and chronic toxicities, and better speech and swal-lowing functions. Techniques to improve radiation dose conformality around the targettissues while decreasing the radiation dose to the normal tissues should be an integral partof aggressive combined modality therapy. © 2002 Wiley-Liss, Inc.

Key words: tissue compensator; intensity modulation; head and neck cancer; toxicity

Contract grant sponsor: National Institutes of Health; Contract grant number: P01CA40007.*Correspondence to: Bharat B. Mittal, M.D., 251 East Huron Street, Galter Pavilion, Suite LC-178, Chicago, IL 60611.

Phone: (312) 926-3399; Fax: (312) 926-6374; E-mail: [email protected] 27 June 2001; Revised 30 October 2001; Accepted 2 November 2001DOI 10.1002/ijc.10360Published online 15 March 2002 in Wiley InterScience (www.interscience.wiley.com).

Int. J. Cancer (Radiat. Oncol. Invest): 96 (Suppl.) 61–70 (2001)© 2002 Wiley-Liss, Inc. Publication of the International Union Against Cancer

INTRODUCTIONRadiation alone or in combination with surgery hasbeen the standard of care in the management of ad-vanced head and neck squamous cell carcinoma. Arecently published randomized trial documents thelocoregional control rate and survival as well as acuteand chronic toxicities produced when radiation aloneis delivered using standard fractionation or alteredfractionation to treat advanced head and neck cancers(AHNCs) [1].

Over the last decade, the intensity of therapyusing chemotherapy and radiation has increased, re-sulting in decreased locoregional failure and im-proved survival [2–7]. Due to the aggressive nature ofthese treatments, toxicities have also increased. It isessential to document such toxicities to assess thebenefit of multimodality therapy. Biochemical, phys-ical, and technical measures should be implementedto reduce the incidence of these toxicities.

This study was undertaken to test the associationbetween the use of missing tissue compensators andthe ability of forward-planned, intensity-modulatedradiation therapy to deliver a uniform dose across theradiation field and decrease the rate of acute andchronic toxicities observed in the management ofAHNC.

MATERIALS AND METHODSA total of 39 patients with AHNC were entered in anintramural Phase II concomitant chemoradiation trialand an NIH-funded Cancer Control Science Programfor Head and Neck Cancer Rehabilitation (CCSP-HNCR). These patients were treated fairly uniformlyusing parallel-opposed radiation beams that gave highdoses to the swallowing and speech organs. The treat-ment consisted of concomitant radiation and chemo-therapy delivered over a period of 5 days followed bya 9-day break. The radiation was delivered at 150 cGyBID. The chemotherapy was comprised of Paclitaxel(Taxol), 5 FU, and hydrea. The 2-week cycle wasrepeated four to five times. Eighteen of 39 patientswere treated using tissue or dose compensation(TDC); the remaining 21 patients were radiated with-out tissue or dose compensation (NTDC).

The first seven of the 39 patients were alterna-tively assigned to the TDC (three patients) or NTDC(four patients) groups. The remaining 32 patientswere prospectively randomized to the TDC or NTDCgroups.

Two methods were employed to modulate theradiation beam in order to achieve a relatively uni-form dose throughout the treatment volume: 1) alu-minum or Cerrobend missing tissue compensators, or2) segmented multifleaf collimator (MLC) fields ob-

tained from forward planning in order to obtain doseuniformity. The first method adjusts the beam fluencebased on missing tissue while ignoring the perturba-tion caused by detailed scatter calculations, whereasthe second method adjusts the beam fluence usingsequential shrinking fields to compensate for calcu-lated excess dose as determined from 3D scatter cal-culations. However, experiments with a home-madehead phantom molded out of candle wax revealed thatthe midsagittal dose distribution, as recorded on ver-ification film, was not significantly different for thetwo methods.

Dose calculations are reported in two planes: thecentral axis (CA) plane (Plane 1) and a plane throughthe thinnest part within the radiation field (Plane 2).For patients in whom compensators were used, dosecalculations were made with and without the compen-sator for comparative purposes. The dose distributionwas observed in multiple planes.

Acute treatment toxicities are reported using Na-tional Cancer Institute (NCI) common toxicity criteria(CTC) v. 2.0, while chronic toxicities are reportedusing Radiation Therapy Oncology Group (RTOG)criteria and the Subjective Objective ManagementAnalytic (SOMA) scale [8,9]. To be able to fullydistinguish acute from chronic toxicities, �90 daysposttreatment was used to score any chronic toxicity.

Swallowing function was examined with themodified barium swallowing procedure [10] usingvideofluorography (VFG). Each patient attempted tocomplete two swallows each of 1, 3, 5, and 10 ml ofbarium liquid and 1 ml of barium paste. Boluses wereadministered from a teaspoon or by slow release froma syringe. Fluoroscopic data were recorded on a 3

4-inch

videotape at 30 frames per second. During the study,the fluoroscopy tube was focused on the lips anteri-orly, the cervical vertebrae posteriorly, the soft palatesuperiorly, and the bifurcation of the esophagus andairway inferiorly. Speech tasks consisted of an audiorecording of a 6 to 7-min conversational speech sam-ple and a reading of the sentence version of theFisher-Logemann Test of Articulation Competence[11]. Data reduction for swallowing and speech wascompleted according to methods described by Paulo-ski et al. [12]. Oropharyngeal swallowing efficiency(OPSE), defined as the approximate percentage of thebolus swallowed into the esophagus divided by totaltransit time, is a global measure that describes theinteraction of the speed of movement of the bolus andthe safety and efficiency of the mechanism in clearingmaterial from the oropharynx while preventing aspi-ration [13].

Each patient’s salivary production was quanti-fied pretherapy; and at several points posttherapy bytaking the difference in the weight of a folded sterile

62 Mittal et al.: Tissue/Dose Compensation

sponge (10 � 10 cm kerlix, 12 ply; Kendall Co.,Mansfield, MA) before and after chewing for 2 min [14].

Prospective quality of life (QOL) assessmentincluded the following well-validated instruments: theFunctional Assessment of Cancer Therapy – Head andNeck Version (FACT-H&N) [15,16], the Perfor-mance Status Scale for Head and Neck Cancer (PSS-HN) [17,18], and selected items from the McMasterRadiotherapy Questionnaire [19], which assesses pa-tients’ perceptions of treatment-related side effects[20,21]. Patients were assessed pretreatment, duringtreatment, and at 3 months posttreatment. QOL anal-yses aimed to examine the group (TDC vs. NTDC)differences at 3 months, while controlling for pretreat-ment values. For PSS-HN subscales and McMasteritems, patients were categorized, based on a specifiedvalue indicating moderate to severe dysfunction, ashaving improved, stayed the same, or worsened. Forexample, if a patient scored above 50 on the Nor-malcy of Diet scale pretreatment and 50 or belowposttreatment, he/she would be coded as “worsened.”Categorization was done separately for each subscaleor item [18,20,21].

The TDC and NTDC groups were comparedusing the t-test for continuous measures and Fisher’sExact test for dichotomous measures [22]. Swallow-ing and speech measures were compared between thetwo groups by using analysis of covariance [22] with

baseline measures as the covariate. Differences inQOL measures (% improved, % same, % worse) werecompared between the two groups through Fisher’sExact test. Pretreatment minus 3-month differencescores on the FACT were compared between the twopatient groups using independent sample t-tests [22],while statistical analyses were done using SAS (Cary,NC) [23].

RESULTSOf 39 patients entered in this study, 18 were irradiatedusing tissue or dose compensation (TDC group) and21 without tissue or dose compensation (NTDCgroup). There were no significant differences betweenthe two groups with reference to gender, race, age,irradiated field, site or stage of tumors, and meanlength of follow-up (Table 1). There were no statisti-cally significant differences between the two groupsin the number of chemotherapy and radiotherapy cy-cles, radiation field size, number of fractions, thechemotherapy drug doses, or the midplane dose at thecentral axis (Table 2). However, the patients treatedwith TDC had a smaller radiation dose gradient(Fig. 1) across the treatment volume (Plane 1 maxi-mum dose P � 0.01 and Plane 2 maximum dose P �0.001). Patients in the TDC group required signifi-cantly fewer unscheduled treatment breaks of 1 ormore weeks (2 out of 18 or 11% of patients),

Table 1. Patient Characteristics

NTDC (n � 21) TDC (n � 18) P-value

GenderMale 15 (71%) 13 (72%) .99Female 6 (29%) 5 (2%)

RaceWhite 17 (81%) 17 (94%) .61Black 2 0Other 2 1

Age (yr)Mean (range) 57 (34–77) 55 (35–75) .48Radiation Field

Entire Larynx 16 (76%) 15 (83%) .70Supraglottic 5 3

Larynx OnlyOropharynx 21 (100%) 18 (100%)Bilateral Parotids 21 (100%) 18 (100%)

Primary tumor siteOropharynx 8 (38%) 9 (50%) .75Nasopharynx 3 (14%) 1 (6%)Hypopharynx 5 (24%) 2 (11%)Larynx 2 (10%) 3 (17%)Unknown 3 (14%) 3 (17%)

StageIII 3 (14%) 2 (11%)IV 18 (86%) 16 (89%) .99

Mean follow-up in months (range) 16 (3–43) 22 (8–40) .08

TDC: tissue/dose compensation; NTDC: no tissue/dose compensation.

Mittal et al.: Tissue/Dose Compensation 63

compared with 43% (9 out of 21) of the patients in theNTDC group (P � 0.04, Table 2).

Acute Treatment Toxicity (CTC Criteria)Patients were monitored for local acute toxicity dur-ing and up to 90 days posttreatment. Table 3 summa-rizes the Grade 3 or 4 toxicities observed in the twopatient groups. There were no significant differencesin disorders except for the pain category. However,there was a trend toward more acute toxicities in theNTDC group. As a result of more acute toxicities,patients in the NTDC group required more treatmentbreaks (Table 2).

Chronic Toxicity (RTOG)Chronic toxicity was defined as toxicity observed�90 days posttreatment. Table 4 shows the Grade 3or 4 worst chronic toxicities observed in TDC and theNTDC groups. Skin toxicity was statistically signifi-cantly higher in the NTDC group. In most of theorgans studied there is a definite trend toward higher,Grade 3 or 4 toxicities in NTDC group. A similartrend toward higher toxicity was observed at the lastfollow-up for the two groups of patients (data notshown).

Chronic Toxicity (SOMA Scale)There were no statistically significant differences inthe worst toxicities between the TDC and NTDCgroups using the SOMA scale (Table 5). However,there was a definite trend toward higher SOMA scalescores in the NTDC group, indicating greater toxici-ties in this group of patients (Table 5). The similartrend of higher toxicity was observed at the last fol-low-up between the two groups of patients.

Descriptive AnalysisIn the NTDC group, four patients developed post-cricoid or proximal esophageal strictures, while threeadditional patients developed severe complications:laryngeal strictures, laryngeal necrosis, and mandibu-lar fracture. None of the patients in the TDC groupdeveloped strictures, necrosis, or fractures (Table 6).

Saliva WeightThe mean salivary weight (SEM) pretreatment and at3 months posttreatment was 4.07 (0.51) vs. 3.90(0.62) and 1.80 (0.75) vs. 0.79 (0.27) g in the NTDCand TDC groups, respectively. There was no signifi-cant difference in salivary secretions pretreatment andup to 3 months posttreatment between the TDC andNTDC patient groups. Salivary secretions continuedto decrease with time and did not recover in eithergroup of patients.

Oral IntakePatients in the TDC group were able to maintainbetter oral intake at all time points, although notstatistically significantly so. Table 7 summarizes thenumber of patients whose oral intake was �50% oftheir nutrition in the TDC and NTDC groups.

Swallowing Data (VFG Studies)Not all patients were able to swallow all the trials ofeach consistency because of refusal to swallow, dif-ficulty in swallowing, or the speech-language pathol-ogist’s judgment that the clinical risk was too great tointroduce or continue with a specific consistency dur-ing the VFG evaluation. At 3 months posttreatment,patients in the TDC group were able to swallow alltested bolus types in higher percentages than the pa-

Table 2. Treatment Data: Cumulative Mean RT/ChemotherapyDoses (SEM)

NTDC (n � 21) TDC (n � 18) P-value

No. of cycles:4 4 45 17 (81%) 14 (78%) 0.99

Taxol dose (mg) 864 (52) 836 (61) 0.895FU dose (mg) 27,635 (885) 26,552 (1035) 0.46Hydrea dose (gms) 27 (2) 26 (1) 0.86Radiation field size**

Primary site & regional nodes 16.1 (2.4) 15.7 (2.6) 0.64Supraclavicular field 14.8 (3.3) 13.3 (1.6) 0.09

Midplane RT dose 7014 (113) 6983 (130) 0.93Plane 1 max. dose 7625 (151) 7265 (143) 0.01*Plane 2 max. dose 8378 (165) 7355 (141) �0.001*Patients with treatment breaks 9 (43%) 2 (11%) 0.04*Number of fractions 47 (1) 45 (2) 0.70

*P � 0.05.**Equivalent square in centimeters.TDC: tissue/dose compensation; NTDC: no tissue/dose compensation.


Fig. 1. Percent isodose distribution in the sagittal plane. A: Without tissue/dose compensation (NTDC). B: With tissue/dosecompensation (TDC).


tients in the NTDC group and significantly more sowith the 3 and 5 ml volumes (Table 8). There were nostatistically significant differences in the swallowingmeasures between the TDC and NTDC groups at 3months posttreatment. However, there was a definitetrend of better swallowing measures, including theglobal measure of oropharyngeal swallowing effi-ciency (OPSE) in the group of patients treated withTDC (Table 9).

Speech MeasuresTable 10 summarizes the speech data for the TDC andNTDC groups at 3 months posttreatment. There were

no statistically significant differences between the twogroups. However, individual consonant speech soundswere consistently more correctly produced in the TDCgroup. The difference in correct articulation of allconsonants approaches significance in favor of theTDC group.

Quality of LifeOf the 39 patients enrolled in the study, pretreatmentand 3-month follow-up data are available on 26, 13 ineach group. Table 11 presents the number and per-centage of patients by group whose symptoms orperformance was worse at 3 months when comparedto pretreatment. Eight patients (62%) in the NTDCgroup had more restricted diets at 3 months thanpretreatment (i.e., went from above 50 to 50 or belowon the diet scale), compared to five (38%) patients inthe TDC group. The pattern of change in difficultywith swallowing was statistically significantly differ-ent between the two groups, with more patients in theNTDC group getting worse (9 vs. 5). On many of the

Table 3. Acute Toxicity <90 DaysPosttreatment (Grade 3 or 4 CommonToxicity Criteria)

NTDC(n � 21)

TDC(n � 18) P-value

Dermatitis 13 (62%) 9 (50%) 0.53Mucositis 19 (90%) 11 (61%) 0.06Dysphagia 14 (67%) 9 (50%) 0.34Xerostomia 0 (0%) 0 (0%) —Pain 14 (67%) 5 (28%) 0.02*Weight loss** 3 (14%) 0 (0%) 0.23Voice changes 2 (10%) 4 (22%) 0.39

*P � 0.05**Most of the patients received gastric tube feeding in addition to maintain-ing oral intake.TDC: tissue/dose compensation; NTDC: no tissue/dose compensation.

Table 4. Worst Chronic Toxicity >90 DaysPosttreatment (Grade 3 or 4 RadiationTherapy Oncology Group Toxicity Criteria)

NTDC(n � 21)


Skin 5 (24%) 0 (0%) 0.05*Mucous membrane 0 (0%) 0 (0%) —Dysphagia 9 (43%) 4 (22%) 0.31Salivary gland 8 (38%) 4 (22%) 0.32Mandible 1 (5%) 0 (0%) 0.99Larynx 2 (10%) 1 (6%) 0.99

*P � 0.05.TDC: tissue/dose compensation; NTDC: no tissue/dose compensation.

Table 5. SOMA Scale* Mean (SEM)at Last Follow-Up

NTDC(n � 21)


Skin/subcutaneous 0.51 (0.09) 0.30 (0.05) 0.06Mucosa 0.62 (0.08) 0.48 (0.09) 0.15Salivary gland 2.72 (0.19) 2.50 (0.17) 0.16Mandible 0.18 (0.18) 0 (0) 0.32Larynx 0.43 (0.08) 0.32 (0.09) 0.07

*S � subjective; O � objective; M � management; A � analytic.TDC: tissue/dose compensation; NTDC: no tissue/dose compensation.

Table 6. Major Complications withinRadiation Field Requiring MedicalIntervention

NTDC(n � 21)

TDC(n � 18)

Post-cricoid strictures 4 0Laryngeal necrosis 1 0Laryngeal stricture 1 0Mandibular fracture 1 0


Table 7. Oral Intake; Number (Percent) with>50% Oral Intake

NTDC TDC P-value

Pretreatment 16/18 (89%) 18/18 (100%) 0.491 month 7/15 (47%) 11/17 (65%) 0.483 months 7/11 (64%) 10/15 (67%) 0.996 months 7/12 (58%) 13/16 (81%) 0.23


Table 8. Ability to Swallow Various BolusTypes by Group at 3 Months Posttreatment

Bolus type

NTDC (n � 8)Number(percent)

TDC (n � 12)Number(percent) P-value

1 ml liquid 7 (88%) 12 (100%) 0.403 ml liquid 4 (50%) 12 (100%) 0.01*5 ml liquid 1 (13%) 11 (92%) �0.001*10 ml liquid 2 (25%) 9 (75%) 0.06Paste 5 (63%) 11 (92%) 0.20

*P � 0.05.TDC: tissue/dose compensation; NTDC: no tissue/dose compensation.


other performance outcomes and functions/symptomsevaluated, there was a trend for more patients in theNTDC group to be more symptomatic at 3 monthsposttreatment than they were pretreatment. In con-trast, there were no significant differences nor trendtowards differences on any of the FACT subscales oron the overall FACT.

DISCUSSIONThe therapeutic gains obtained with the use of aggres-sive treatments are offset by the widely used standardradiotherapeutic techniques that treat irregularlyshaped body parts, such as head and neck and breastareas, and result in excessive normal tissue doses thatcan potentially cause increased normal tissue compli-cations [24–27]. The intensity of the radiation beam

can be modulated either to deliver uniform doses todecrease dosimetric “hot spots” in the normal tissues,as done in our study, or the photon fluence can bechanged over time and space to increase dose confor-mality to the target tissue and decrease radiation tonormal tissues [28,29]. 3D conformal techniques todeliver radiation can also be employed to improve thetherapeutic ratio in the management of head and neckcancers [30,31].

There are no published clinical studies of headand neck cancers that systematically document thepreservation of normal tissue function with the use ofTDC. Few clinical studies of head and neck cancershave utilized beam modulation, including intensity-modulated radiotherapy (IMRT), to preserve normalorgan function. Eisbruch et al. [32,33] and Dawson etal. [34] used static, multisegmental IMRT to treat agroup of selected patients with head and neck cancerto preserve salivary gland function without compro-mising target coverage. Chao et al. [35] were also ableto spare salivary function and improve QOL by mod-ulating radiation intensity. Our study systematicallydocuments the decrease in acute and late complica-tions and better QOL, speech and swallowing func-tions with the use of a 3D tissue compensator andforward-planned static multisegment radiotherapy toobtain uniform dose distribution.

In this study, there were no significant differ-ences in patient characteristics, tumor stage and sites,

Table 9. Swallowing Measures: Mean (SEM)for Boluses of 1 ml Liquid and Any Pasteat 3 Months Posttreatment

NTDC TDC

P-value

1 ml liquid

n � 6 n � 7

Pharyngealresidue (%) 35.1 (16.0) 12.5 (7.4) 0.23

OPSE (%/s)* 66 (17) 73 (12) 0.7

1 cc Paste

n � 5 n � 7

Pharyngealresidue (%) 27.9 (8.8) 10.5 (3.8) 0.11

OPSE (%/s)* 42 (7) 54 (5) 0.17

*OPSE: oropharyngeal swallowing efficiency (percent per second); TDC:tissue/dose compensation; NTDC: no tissue/dose compensation.

Table 10. Correct Production of SpeechSounds: Mean (SEM) of 3-MonthSpeech Measures

NTDCn � 9

TDCn � 6 P-value

/p, b/ 100 (0) 100 (0) —/t, d/ 90.9 (0) 90.9 (0) —/k, g/ 83.3 (8.6) 100 (9.5) 0.24/M/ 100 (0) 100 (0) —/f, v/ 91.7 (6.2) 100 (6.8) 0.39/�, ð/ 88.6 (4.6) 97.0 (5.1) 0.28/s, z/ 83.3 (13.6) 100 (15.0) 0.45/�, 3/ 70.8 (11.9) 83.0 (13.0) 0.52/h/ 100 (0) 100 (0) —/t�, d3/ 83.3 (12.4) 100 (13.6) 0.39Glides 100 (0) 100 (0) —Nasals 100 (0) 100 (0) —All consonants 88.3 (3.9) 100 (4.3) 0.07


Table 11. Number of Patients, by Group,with More Problems at 3-MonthPosttreatment Than Pretreatment

NTDC(n � 13)


Performance outcome1

Diet (soft foods) 8 (62%) 5 (38%) 0.43Eating in public (limited) 7 (54%) 4 (31%) 0.43Speech (difficult to

understand) 2 (15%) 0 0.48Side effects/symptoms2

Dry mouth 10 (77%) 10 (77%) 0.99Difficulty swallowing 9 (69%) 5 (38%) 0.008*Sticky saliva 8 (61%) 8 (61%) 0.99Throat pain 6 (46%) 5 (38%) 0.99Mouth pain 5 (38%) 4 (33%) 0.99Hoarse voice 5 (38%) 3 (23%) 0.67Difficulty tasting 2 (16%) 4 (31%) 0.64

*P � 0.051Data indicate percent of patients scoring above 50 pretreatment and 50 orbelow at 3 months on the Performance Status Scale for Head and NeckCancer.2Data indicate percent of patients reporting mild or no problems (4–7 onseven-point Likert scale) pretreatment and moderate to severe problems (1–3)at 3 months posttreatment on selected items from the McMaster RadiotherapyQuestionnaire.TDC: tissue/dose compensation; NTDC: no tissue/dose compensation.


radiated structures, radiation doses in midplane at thecentral axis, number of chemotherapy cycles, anddoses between the TDC and NTDC groups. However,the qualitative comparison of dose distribution be-tween the TDC and NTDC plans demonstrates that15% to 20% of hot spots in the thin portion of theneck were reduced to within 5% of the prescribeddose with the use of TDC. This 10% to 20% higherdose over the prescribed dose in the anterior neck notonly occurs on the skin surface but throughout theanterior volume, including larynx and pharynx at thislocation (Fig. 1). These dosimetric “hot spots” in theNTDC group resulted in increased acute and chronictoxicities, with some of the patients requiring medicalinterventions to manage post-cricoid strictures, laryn-geal stenosis, laryngeal necrosis, and mandibular frac-ture. Because of acute toxicities, patients in the NTDCgroup required a minimum of 1 week unscheduledtreatment breaks in a higher percentage than the TDCgroup. Due to the prolonged acute effects with thetreatment regimen in our study, we used �90 daysposttreatment, as opposed to the RTOG criteria of 90days, from the start of treatment to score chronictoxicities. We were not able to compare dose–volumehistograms between the two groups because CT datawere not available for a number of the patients in theNTDC group. This information would have beenhelpful for further comparison between the twogroups.

There was no difference in saliva weight be-tween the TDC and NTDC patients in our studybecause both groups received high radiation doses tothe salivary glands in excess of the threshold forpermanent xerostomia [33]. We did not observe im-provement in salivary secretion with time in either theTDC or the NTDC group.

Subjective and objective assessments of swal-lowing and speech function also revealed generallybetter functional outcomes in the patients in the TDCgroup. The patients in the TDC group experiencedbetter QOL when assessed by various performanceoutcomes and symptoms. More patients in the TDCgroup were able to take �50% of their nutrition byoral intake than in the NTDC group. More patients inthe TDC group were also able to swallow multiplebolus types, had lower pharyngeal residue, i.e., morenormal OPSE, and a greater percentage of correctpronunciation of all consonants as compared withpatients in the NTDC group. Data on speech andswallowing were available for only a limited numberof patients due to patient dropout. Additionally, not allpatients were able to swallow two trials of each foodconsistency, or the speech-language pathologist mayhave judged it risky to introduce or continue with aspecific consistency during the VFG study. The swal-

lowing dysfunctions observed in our study are similarto the ones reported by Lazarus et al. [36,37] follow-ing chemotherapy � radiation for the treatment ofhead and neck cancers. Impaired swallowing motilitymay be the result of edema, fibrosis, and reducedsalivary flow caused by radiation and chemotherapy.

CONCLUSIONOur results suggest that there is a systematic trendtoward decreased acute and chronic toxicities, betterspeech and swallowing function, and quality of life inthe group of patients treated with TDC to decrease“hot spots” in tissues. The relatively small number ofpatients in the study may explain the lack of statisticalsignificance of our observations in a number of theend-points studied. In order to reduce toxicities andmaintain better functional outcomes, various tech-niques to improve therapeutic ratio should be evalu-ated and potentially become the standard of care in thetreatment of head and neck cancer managed withaggressive multimodality therapy.

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Tissue/DoseCompensationtoReduceToxicity ... · with TDC had a smaller radiation dose gradient (Fig. 1) across the treatment volume (Plane 1 maxi-mum dose P 0.01 and Plane 2 maximum