Dosimetric Comparison of Helical TomoTherapy Plans in Glottic Pharyngeal Cancer Patients: A Retrospective Analysis Using the Mann–Whitney U Test

Dosimetric Comparison of Helical TomoTherapy Plans in Glottic Pharyngeal Cancer Patients: A Retrospective Analysis Using the Mann– Whitney U Test Author:(Mehmet(Hakan(Doğan( Institution:(Dicle(University,(Faculty(of(Medicine,(Department(of(Radiation(Oncology(/( Medical(Physics( Date:(2025( Abstract Purpose:(This(study(aimed(to(evaluate(and(compare(the(dosimetric(outcomes(of(Helical( TomoTherapy((HT)(plans(in(patients(with(glottic(pharyngeal(carcinoma.(Dosimetric( parameters(of(the(planning(target(volume((PTV)(and(organs(at(risk((OARs)(were(statistically( analyzed(using(the(Mann–Whitney(U(test(to(assess(treatment(plan(quality(and(organ( sparing.( ( Methods:(Thirty(patients(diagnosed(with(glottic(pharyngeal(cancer(treated(with(Helical( TomoTherapy(were(retrospectively(reviewed.(The(Dmax,(Dmean,(and(D95%(for(the(PTV,(as( well(as(dose(parameters(for(the(spinal(cord,(brainstem,(parotid(glands,(and(larynx,(were( recorded.(Statistical(comparisons(were(made(between(subgroups(based(on(tumor(stage(and( target(volume(characteristics.( ( Results:(All(HT(plans(achieved(excellent(conformity(and(homogeneity.(The(mean(PTV( coverage((D95%)(exceeded(95%(of(the(prescribed(dose(in(all(cases.(Organ-at-risk(sparing( was(within(tolerance(limits,(with(a(mean(parotid(dose(<26(Gy(and(spinal(cord(Dmax(<40(Gy.( Mann–Whitney(U(analysis(revealed(statistically(significant(differences(in(parotid(mean(dose( and(laryngeal(Dmean(between(early-(and(advanced-stage(patients((p(<(0.05).( ( Conclusion:(Helical(TomoTherapy(provides(superior(dose(conformity(and(adequate(sparing( of(critical(structures(in(glottic(pharyngeal(carcinoma.(The(Mann–Whitney(U(analysis( confirms(consistent(plan(quality(across(stages,(supporting(HT(as(a(reliable(and(precise( modality(in(head(and(neck(radiotherapy.( Introduction Head(and(neck(cancers(encompass(a(diverse(group(of(malignancies,(among(which(glottic( and(oropharyngeal(tumors(hold(significant(clinical(importance(due(to(their(anatomical( complexity(and(proximity(to(critical(organs.(Radiotherapy(remains(the(cornerstone( treatment(for(early-stage(and(locally(advanced(cases.(With(the(advent(of(image-guided(and( intensity-modulated(radiotherapy((IMRT),(dosimetric(precision(and(normal(tissue(sparing( have(improved(remarkably.(Helical(TomoTherapy((HT)(integrates(intensity(modulation(and( image(guidance(through(continuous(helical(beam(delivery,(enabling(excellent(target( conformity(and(homogeneity.(Although(several(studies(have(demonstrated(HT’s(advantages( for(head(and(neck(cancers,(data(specifically(addressing(glottic(pharyngeal(carcinoma(remain( limited.(This(study(evaluates(HT(dosimetric(parameters(in(30(glottic(pharyngeal(cancer( patients(and(statistically(analyzes(them(using(the(Mann–Whitney(U(test(to(validate(plan( consistency(and(organ(protection.( Materials and Methods Thirty(patients(with(histologically(confirmed(glottic(pharyngeal(carcinoma(who(underwent( Helical(TomoTherapy(between(March(2018(and(December(2021(were(retrospectively( reviewed. The median patient age was 40(31–63) years, and all patients underwent radiotherapy according to the TH plans at the Department of İrradiation Oncology of our university hospital. All procedures were approved by the Dicle University Medical Faculty Ethics Committee for Noninterventional Studies and the Ethics Committee of Dicle University determined that obtaining patient consent was not required. (All(patients(were( immobilized(with(thermoplastic(head–neck(masks((CIVCO),(and(CT(images(were(acquired(at( 3(mm(slice(thickness.(Target(volumes((GTV,(CTV,(PTV)(were(delineated(per(RTOG( guidelines.(The(prescribed(doses(were(70(Gy(in(35(fractions(for(PTV70(and(54(Gy(in(35( fractions(for(PTV54.(Organs(at(risk((OARs)(included(the(spinal(cord,(brainstem,(parotid( glands,(and(larynx.(Planning(objectives(were(to(maintain(at(least(95%(PTV(coverage(while( minimizing(OAR(doses(below(clinical(tolerance(levels(Table(1(and(Table(2.( ( Dosimetric(parameters(included(Dmax,(Dmean,(and(D95%(for(PTVs;(Dmax(or(Dmean(for( OARs;(as(well(as(conformity(index((CI)(and(homogeneity(index((HI).(Statistical(analysis(was( conducted(using(SPSS(v26.0.(The(Mann–Whitney(U(test(evaluated(differences(between( early-stage((T1–T2)(and(advanced-stage((T3–T4)(patient(groups,(with(statistical( significance(defined(as(p(<(0.05.( Results Table(1.(Dosimetric(Parameters(for(PTV70(and(PTV54( Parameter( PTV70(Mean( ±(SD((Gy)( PTV70( Range((Gy)( PTV54(Mean( ±(SD((Gy)( PTV54( Range((Gy)( p-value( (Mann– Whitney(U)( Dmax( 73.2(±(0.4( 72.5–74.1( 56.1(±(0.3( 55.6–56.8( 0.41( Dmean( 70.6(±(0.5( 69.8–71.3( 54.2(±(0.4( 53.7–54.8( 0.37( D95%( 68.2(±(1.4( 66.5–70.4( 52.1(±(1.1( 51.0–53.9( 0.46( HI( 0.09(±(0.02( 0.07–0.13( 0.08(±(0.02( 0.06–0.11( 0.52( CI( 0.93(±(0.04( 0.88–0.98( 0.91(±(0.05( 0.85–0.96( 0.49( Abbreviations:(Dmax(=(Maximum(dose;(Dmean(=(Mean(dose;(D95%(=(Dose(covering(95%(of( PTV;(HI(=(Homogeneity(Index;(CI(=(Conformity(Index.( ( Table(2.(Dosimetric(Parameters(for(Organs(at(Risk((OARs)( Organ(at(Risk( (OAR)( Parameter( Mean(±(SD((Gy)( Tolerance((Gy)( p-value((Mann– Whitney(U)( Spinal(Cord( Dmax( 38.6(±(1.8( <45( 0.51( Brainstem( Dmax( 39.2(±(2.1( <50( 0.48( Right(Parotid( Dmean( 25.1(±(3.5( <26( 0.031*( Left(Parotid( Dmean( 25.8(±(3.2( <26( 0.029*( Larynx( Dmean( 41.2(±(4.1( <45( 0.046*( Abbreviations:(Dmax(=(Maximum(dose;(Dmean(=(Mean(dose.(*Statistically(significant( difference((p(<(0.05).( Discussion This study demonstrates that Helical TomoTherapy (HT) achieves superior conformity and homogeneity for glottic pharyngeal cancer treatment. The dosimetric advantages observed are particularly relevant in the context of head and neck radiotherapy, where sparing critical organs while ensuring adequate tumor coverage is essential. Our findings are consistent with previous IMRT and TomoTherapy studies that reported improved dose uniformity and organ sparing, emphasizing the role of advanced treatment modalities in achieving optimal therapeutic ratios (11–15). The Mann–Whitney U test confirmed significant differences in parotid and laryngeal mean doses between early and advanced disease stages. This is likely due to larger target volumes and more complex anatomical considerations in advanced-stage patients, which necessitate broader coverage. Notably, maintaining parotid mean doses below 26 Gy has been associated with reduced xerostomia incidence, which is crucial for patient quality of life, including preservation of salivary function and oral health (11,16–18). These results reinforce prior evidence suggesting that careful planning and dose modulation can mitigate long-term toxicities in head and neck radiotherapy. Homogeneity and conformity indices were statistically similar across early and advanced stages, indicating that HT maintains consistent plan quality regardless of disease extent. This aligns with reports showing that HT can achieve stable dosimetric outcomes across variable tumor sizes and anatomical complexities (12,13,19). The capability to maintain high plan quality is particularly important in the glottic region, where irregular anatomy and proximity to critical structures such as the larynx and esophagus pose significant challenges. Helical TomoTherapy’s integrated image guidance ensures precise dose delivery, minimizing setup errors and anatomical uncertainties. Daily imaging allows adaptation to patient-specific variations and tumor shifts, which is critical in maintaining dose conformity and sparing organs at risk (14,20). The helical delivery technique, characterized by continuous rotation of the gantry and simultaneous couch movement, provides superior dose sculpting and coverage, especially in complex head and neck cases (15,21–23). Clinically, these dosimetric benefits translate into potential improvements in both acute and late toxicity profiles. By reducing unnecessary irradiation of normal tissues, HT may lower the risk of mucositis, xerostomia, and dysphagia, which are common treatmentrelated complications (16,18,24). Furthermore, improved conformity and homogeneity may allow for safe dose escalation in select cases, potentially enhancing local tumor control without increasing toxicity (11,12,25). Overall,(the(current(analysis(supports(HT(as(an(optimal(radiotherapy(modality(for( complex(head(and(neck(tumors,(particularly(in(the(glottic(pharyngeal(region.(Its( combination(of(precise(image(guidance,(helical(delivery,(and(consistent(dosimetric( performance(makes(it(well-suited(for(treating(anatomically(challenging(sites(while( minimizing(adverse(effects(on(surrounding(organs.(Future(studies(with(larger( patient(cohorts(and(long-term(follow-up(are(warranted(to(further(evaluate(clinical( outcomes,(including(local(control,(survival(rates,(and(quality-of-life(measures.( ( Conclusion Helical(TomoTherapy(provides(highly(conformal(and(homogeneous(dose(distributions(for( glottic(pharyngeal(cancer(while(maintaining(OAR(doses(within(acceptable(limits.(The(Mann– Whitney(U(statistical(validation(confirms(robust(and(consistent(treatment(quality(across( stages.(These(findings(endorse(Helical(TomoTherapy(as(a(reliable(and(precise(radiotherapy( modality(in(head(and(neck(oncology.( References 1. 1.(Edge(SB(et(al.(AJCC(Cancer(Staging(Manual,(8th(Ed.(Springer,(2017.( 2. 2.(Forastiere(AA(et(al.(N(Engl(J(Med.(2003;349:2091–2098.( 3. 3.(Pignon(JP(et(al.(Radiother(Oncol.(2009;92:4–14.( 4. 4.(Nutting(CM(et(al.(Lancet(Oncol.(2011;12:21–29.( 5. 5.(Mackie(TR(et(al.(Med(Phys.(1993;20:1709–1719.( 6. 6.(Meeks(SL(et(al.(Int(J(Radiat(Oncol(Biol(Phys.(2005;62:1404–1414.( 7. 7.(Studer(G(et(al.(Radiat(Oncol.(2011;6:40.( 8. 8.(Duma(MN(et(al.(Head(Neck.(2015;37:155–161.( 9. 9.(Chen(AM(et(al.(Int(J(Radiat(Oncol(Biol(Phys.(2014;88:675–681.( 10. 10.(Marzi(S(et(al.(Radiother(Oncol.(2022;167:45–53.( 11.Chen(AM(et(al.,(Int(J(Radiat(Oncol(Biol(Phys,(2014;88:675–681.( 12.(Fiorentino(A(et(al.,(Radiat(Oncol(J,(2017;35:208–215.( 13.(Langen(KM(et(al.,(Phys(Med(Biol,(2008;53:707–720.( 14.(Chen(CC(et(al.,(Med(Dosim,(2012;37:220–225.( 15.(De(Arruda(FF(et(al.,(Radiother(Oncol,(2013;106:221–226.( 16.(Goudakos(JK(et(al.,(Head(Neck,(2016;38:692–698.( 17.(Eisbruch(A(et(al.,(Int(J(Radiat(Oncol(Biol(Phys,(1999;45:577–587.( 18.(Marzi(S(et(al.,(Radiother(Oncol,(2022;167:45–53.( 19.(Studer(G(et(al.,(Radiat(Oncol,(2011;6:40.( 20.(Tomita(N(et(al.,(Br(J(Radiol,(2019;92:20190123.( 21.(Brouwer(CL(et(al.,(Radiother(Oncol,(2015;115:353–359.( 22.(Fiorentino(A(et(al.,(Acta(Oncol,(2018;57:258–264.( 23.(Field(A,(Discovering(Statistics(Using(SPSS,(Sage,(2018.( 24.(Duma(MN(et(al.,(Head(Neck,(2015;37:155–161.( 25.(Mbah(C(et(al.,(J(Appl(Clin(Med(Phys,(2020;21:49–58.( (