To review the pathophysiology of early and late radiation-related tissue changes, methods to differentiate these changes from disease recurrence, and treatment of these changes in the irradiated larynx.
Data Sources
Peer-reviewed publications.
Review Methods
PubMed database search.
Conclusions/Implications for Practice
Early and late radiation-related changes in the larynx manifest variably between individual patients. Severe radiation-related tissue changes in the larynx and recurrent malignancy share many clinical characteristics, and the presence of malignancy must be considered in these patients. Positron emission tomography may help select patients who need operative biopsy to rule out recurrence. In patients with a cancer-free but dysfunctional larynx, both surgical and nonsurgical treatment options, including hyperbaric oxygen, are available for attempted salvage. Further investigation is needed before hyperbaric oxygen can be considered standard-of-care treatment for these patients.
HartlDMFerlitoABrasnuDF. Evidence-based review of treatment options for patients with glottic cancer. Head Neck. 2011;33:1638-1648.
2.
GourinCGForastiereAASanguinetiGMarurSKochWMBristowRE. Volume-based trends in laryngeal cancer surgery. Laryngoscope. 2011;121:77-84.
3.
GanlyIPatelSGMatsuoJ. Results of surgical salvage after failure of definitive radiation therapy for early-stage squamous cell carcinoma of the glottic larynx. Arch Otolaryngol Head Neck Surg. 2006;132:59-66.
4.
RodriguezCPAdelsteinDJRybickiLA. Clinical predictors of larynx preservation after multiagent concurrent chemoradiotherapy. Head Neck. 2008;30:1535-1542.
5.
PatelUAHowellLK. Local response to chemoradiation in T4 larynx cancer with cartilage invasion. Laryngoscope. 2011;121:106-110.
6.
McLaughlinMPParsonsJTFeinDA. Salvage surgery after radiotherapy failure in T1-T2 squamous cell carcinoma of the glottic larynx. Head Neck. 1996;18:229-235.
7.
HutchesonKAAlvarezCPBarringerDAKupfermanMELapinePRLewinJS. Outcomes of elective total laryngectomy for laryngopharyngeal dysfunction in disease-free head and neck cancer survivors. Otolaryngol Head Neck Surg. 2012;146:585-590.
8.
SorensenHHansenHSThomsenKA. Partial laryngectomy following irradiation. Laryngoscope. 1980;90:1344-1349.
9.
FrancisDOYuehBWeymullerEAJrMeratiAL. Impact of surveillance on survival after laryngeal cancer in the medicare population. Laryngoscope. 2009;119:2337-2344.
10.
O’BrienPC. Tumour recurrence or treatment sequelae following radiotherapy for larynx cancer. J Surg Oncol. 1996;63:130-135.
11.
BahadurSAmatyaRCKackerSK. The enigma of post-radiation oedema and residual or recurrent carcinoma of the larynx and pyriform fossa. J Laryngol Otol. 1985;99:763-765.
12.
LedermanM. Radiation therapy in cancer of the larynx. JAMA. 1972;221:1253-1254.
13.
HarfoucheGMartinMT. Response of normal stem cells to ionizing radiation: a balance between homeostasis and genomic stability. Mutat Res. 2010;704:167-174.
14.
AlexanderFW. Micropathology of radiation reaction in the larynx. Ann Otol Rhinol Laryngol. 1963;72:831-841.
15.
FergusonBJHudsonWRFarmerJCJr. Hyperbaric oxygen therapy for laryngeal radionecrosis. Ann Otol Rhinol Laryngol. 1987;96:1-6.
16.
NakashimaTTomitaHTsudaSChitoseS. Radiotherapy of the neck influences the distribution of laryngeal secretory glands. J Laryngol Otol. 2005;119:976-980.
17.
DorrW. Radiation effect in normal tissu—principles of damage and protection. Nuklearmedizin. 2010;49(suppl 1):S53-S58.
18.
Di NicolaLGravinaGLMaramponF. The impact of conventional or hypofractionated radiotherapy on voice quality and oncological outcome in patients with early glottic cancer. Oncol Rep. 2010;24:1383-1388.
19.
van der MolenLvan RossumMAJacobiI. Pre- and posttreatment voice and speech outcomes in patients with advanced head and neck cancer treated with chemoradiotherapy: expert listeners’ and patient’s perception. J Voice. 2012;26:664e625-633.
20.
HarrisonLBSolomonBMillerSFassDEArmstrongJSessionsRB. Prospective computer-assisted voice analysis for patients with early stage glottic cancer: a preliminary report of the functional result of laryngeal irradiation. Int J Radiat Oncol Biol Phys. 1990;19:123-127.
21.
BibbyJRCottonSMPerryACorryJF. Voice outcomes after radiotherapy treatment for early glottic cancer: assessment using multidimensional tools. Head Neck. 2008;30:600-610.
22.
AdamsGBurnettRMillsEPennimentM. Objective and subjective changes in voice quality after radiotherapy for early (T1 or T2, N0) laryngeal cancer: a pilot prospective cohort study. Head Neck. 2013;35:376-380.
23.
FitzgeraldPJKochRJ. Delayed radionecrosis of the larynx. Am J Otolaryngol. 1999;20:245-249.
24.
FilntisisGAMoonREKraftKLFarmerJCScherRLPiantadosiCA. Laryngeal radionecrosis and hyperbaric oxygen therapy: report of 18 cases and review of the literature. Ann Otol Rhinol Laryngol. 2000;109:554-562.
25.
FungKLydenTHLeeJ. Voice and swallowing outcomes of an organ-preservation trial for advanced laryngeal cancer. Int J Radiat Oncol Biol Phys. 2005;63:1395-1399.
26.
CaudellJJCarrollWRSpencerSABonnerJA. Examination of laryngoesophageal dysfunction-free survival as an endpoint in nonsurgical treatment of squamous cell carcinomas of the larynx and hypopharynx. Cancer. 2011;117:4447-4451.
27.
LambertLFortinBSoulieresD. Organ preservation with concurrent chemoradiation for advanced laryngeal cancer: are we succeeding?Int J Radiat Oncol Biol Phys. 2010;76:398-402.
28.
ForastiereAAZhangQWeberRS. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol. 2013;31:845-852.
29.
OppenheimerRWKrespiYPEinhornRK. Management of laryngeal radionecrosis: animal and clinical experience. Head Neck. 1989;11:252-256.
30.
KeeneMHarwoodARBryceDPvan NostrandAW. Histopathological study of radionecrosis in laryngeal carcinoma. Laryngoscope. 1982;92:173-180.
31.
ChandlerJR. Radiation fibrosis and necrosis of the larynx. Ann Otol Rhinol Laryngol. 1979;88:509-514.
32.
MintzDRGullanePJThomsonDHRubyRR. Perichondritis of the larynx following radiation. Otolaryngol Head Neck Surg. 1981;89:550-554.
33.
McGovernFHFitz-HughJSConstableW. Post-radiation perichondritis and cartilage necrosis of the larynx. Laryngoscope. 1973;83:808-815.
34.
MazeronRTaoYLusinchiABourhisJ. Current concepts of management in radiotherapy for head and neck squamous-cell cancer. Oral Oncol. 2009;45:402-408.
35.
MendenhallWMAmdurRJPaltaJR. Intensity-modulated radiotherapy in the standard management of head and neck cancer: promises and pitfalls. J Clin Oncol. 2006;24:2618-2623.
36.
JacobsonASBuchbinderDHuKUrkenML. Paradigm shifts in the management of osteoradionecrosis of the mandible. Oral Oncol. 2010;46:795-801.
37.
EisbruchAKimHMFengFY. Chemo-IMRT of oropharyngeal cancer aiming to reduce dysphagia: swallowing organs late complication probabilities and dosimetric correlates. Int J Radiat Oncol Biol Phys. 2011;81:e93-99.
38.
NguyenNPChiABetzM. Feasibility of intensity-modulated and image-guided radiotherapy for functional organ preservation in locally advanced laryngeal cancer. PLoS One. 2012;7:e42729.
39.
CukurovaICetinkayaEA. Radionecrosis of the larynx: case report and review of the literature. Acta Otorhinolaryngol Ital. 2010;30:205.
40.
StewartJGBrownJRPalmerMKCooperA. The management of glottic carcinoma by primary irradiation with surgery in reserve. Laryngoscope. 1975;85:1477-1484.
41.
WiernikGBatesTDBleehenNM. Final report of the general clinical results of the British Institute of Radiology fractionation study of 3F/wk versus 5F/wk in radiotherapy of carcinoma of the laryngo-pharynx. Br J Radiol. 1990;63:169-180.
42.
FletcherGHLindbergRDHambergerAHoriotJC. Reasons for irradiation failure in squamous cell carcinoma of the larynx. Laryngoscope. 1975;85:987-1003.
43.
GilbertRWLundgrenJAvan NostrandAWKeaneTJ. T3N0M0 glottic carcinoma—a pathologic analysis of 41 patients treated surgically following radiotherapy. Clin Otolaryngol Allied Sci. 1988;13:467-479.
44.
BergerGFreemanJLBriantTDBerryMNoyekAM. Late post radiation necrosis and fibrosis of the larynx. J Otolaryngol. 1984;13:160-164.
45.
KaganARCalcaterraTWardPChanP. Significance of edema of the endolarynx following curative irradiation for carcinoma. Am J Roentgenol Radium Ther Nucl Med. 1974;120:169-172.
46.
WardPHCalcaterraTCKaganAR. The enigma of post-radiation edema and recurrent or residual carcinoma of the larynx. Laryngoscope. 1975;85:522-529.
47.
MillsEE. Early glottic carcinoma: factors affecting radiation failure, results of treatment and sequelae. Int J Radiat Oncol Biol Phys. 1979;5:811-817.
48.
FuKKWoodhouseRJQuiveyJMPhillipsTLDedoHH. The significance of laryngeal edema following radiotherapy of carcinoma of the vocal cord. Cancer. 1982;49:655-658.
49.
FloodLMBrightwellAP. Clinical assessment of the irradiated larynx. Salvage laryngectomy in the absence of histological confirmation of residual or recurrent carcinoma. J Laryngol Otol. 1984;98:493-498.
50.
TurnerSLTiverKW. Radical radiotherapy for carcinoma of the larynx—Westmead Hospital experience. Australas Radiol. 1991;35:242-247.
51.
StevensGCastleGO’BrienCJ. Treatment of early carcinoma of the vocal cords by radiotherapy. Australas Radiol. 1994;38:119-122.
52.
VianiLStellPMDalbyJE. Recurrence after radiotherapy for glottic carcinoma. Cancer. 1991;67:577-584.
53.
SchultzCJCampbellBHFreijeJEBrookBJMcAuliffeTL. Risk factors which predict persistent cancer in the abnormal larynx following definitive irradiation. Eur J Cancer B Oral Oncol. 1995;31B:310-314.
54.
AllenCTJuddNPBuiJDUppaluriR. The clinical implications of antitumor immunity in head and neck cancer. Laryngoscope. 2012;122:144-157.
55.
RowleyHWalshMMcShaneDFraserIO’DwyerTP. Chondroradionecrosis of the larynx: still a diagnostic dilemma. J Laryngol Otol. 1995;109:218-220.
56.
PiotrowskiSM. Laryngectomy as a salvage procedure of the patients with massive postradiation injury of the larynx. Otolaryngol Pol. 2007;61:243-253.
57.
ZbarenPCaversaccioMThoenyHCNuyensMCurschmannJStaufferE. Radionecrosis or tumor recurrence after radiation of laryngeal and hypopharyngeal carcinomas. Otolaryngol Head Neck Surg. 2006;135:838-843.
58.
CastelijnsJAvan den BrekelMWTobiH. Laryngeal carcinoma after radiation therapy: correlation of abnormal MR imaging signal patterns in laryngeal cartilage with the risk of recurrence. Radiology. 1996;198:151-155.
59.
BriggsRJGallimoreAPPhelpsPDHowardDJ. Laryngeal imaging by computerized tomography and magnetic resonance following radiation therapy: a need for caution. J Laryngol Otol. 1993;107:565-568.
60.
de BreeRvan der PuttenLBrouwerJCastelijnsJAHoekstraOSLeemansCR. Detection of locoregional recurrent head and neck cancer after (chemo)radiotherapy using modern imaging. Oral Oncol. 2009;45:386-393.
61.
GrevenKMWilliamsDWIIIKeyesJWJr. Distinguishing tumor recurrence from irradiation sequelae with positron emission tomography in patients treated for larynx cancer. Int J Radiat Oncol Biol Phys. 1994;29:841-845.
62.
McGuirtWFGrevenKMKeyesJWJrWilliamsDWIIIWatsonN. Laryngeal radionecrosis versus recurrent cancer: a clinical approach. Ann Otol Rhinol Laryngol. 1998;107:293-296.
63.
BrouwerJHooftLHoekstraOS. Systematic review: accuracy of imaging tests in the diagnosis of recurrent laryngeal carcinoma after radiotherapy. Head Neck. 2008;30:889-897.
64.
van HoorenACBrouwerJde BreeRHoekstraOSLeemansCRUyl-de GrootCA. The cost-effectiveness of 18FDG-PET in selecting patients with suspicion of recurrent laryngeal carcinoma after radiotherapy for direct laryngoscopy. Eur Arch Otorhinolaryngol. 2009;266:1441-1448.
65.
GuptaTMasterZKannanS. Diagnostic performance of post-treatment FDG PET or FDG PET/CT imaging in head and neck cancer: a systematic review and meta-analysis. Eur J Nucl Med Mol Imaging. 2011;38:2083-2095.
66.
IloabachieKNathanCOAmpilFMorganMLCalditoG. Return of vocal cord movement: an independent predictor of response to nonsurgical management of laryngeal cancers. Laryngoscope. 2007;117:1925-1929.
67.
RohJL. Chondroradionecrosis of the larynx: diagnostic and therapeutic measures for saving the organ from radiotherapy sequelae. Clin Exp Otorhinolaryngol. 2009;2:115-119.
68.
BekirogluFWrightSGrewN. Chondroradionecrosis of larynx following radiotherapy for metastatic neck disease originating from oral carcinoma. Int J Oral Maxillofac Surg. 2007;36:459-461.
69.
StoreGEribeEROlsenI. DNA-DNA hybridization demonstrates multiple bacteria in osteoradionecrosis. Int J Oral Maxillofac Surg. 2005;34:193-196.
70.
AasJAReimeLPedersenK. Osteoradionecrosis contains a wide variety of cultivable and non-cultivable bacteria. J Oral Microbiol. 2010;2.
71.
NasonRCholeRA. Bacterial biofilms may explain chronicity in osteoradionecrosis of the temporal bone. Otol Neurotol. 2007;28:1026-1028.
72.
NaroznyWKuczkowskiJMikaszewskiB. Radionecrosis or tumor recurrence after radiation: importance of choice for HBO. Otolaryngol Head Neck Surg. 2007;137:176-177.
73.
FeldmeierJJHampsonNB. A systematic review of the literature reporting the application of hyperbaric oxygen prevention and treatment of delayed radiation injuries: an evidence based approach. Undersea Hyperb Med. 2002;29:4-30.
HartGBMainousEG. The treatment of radiation necrosis with hyperbaric oxygen (OHP). Cancer. 1976;37:2580-2585.
76.
FeldmeierJJHeimbachRDDavoltDABrakoraMJ. Hyperbaric oxygen as an adjunctive treatment for severe laryngeal necrosis: a report of nine consecutive cases. Undersea Hyperb Med. 1993;20:329-335.
77.
LondonSDParkSSGampperTJHoardMA. Hyperbaric oxygen for the management of radionecrosis of bone and cartilage. Laryngoscope. 1998;108:1291-1296.
78.
NaroznyWSickoZKotJStankiewiczCPrzewoznyTKuczkowskiJ. Hyperbaric oxygen therapy in the treatment of complications of irradiation in head and neck area. Undersea Hyperb Med. 2005;32:103-110.
79.
OridateNHommaASuzukiS. Voice-related quality of life after treatment of laryngeal cancer. Arch Otolaryngol Head Neck Surg. 2009;135:363-368.
80.
BelafskyPCMouadebDAReesCJ. Validity and reliability of the Eating Assessment Tool (EAT-10). Ann Otol Rhinol Laryngol. 2008;117:919-924.
81.
SunTBChenRLHsuYH. The effect of hyperbaric oxygen on human oral cancer cells. Undersea Hyperb Med. 2004;31:251-260.
82.
FeldmeierJCarlUHartmannKSminiaP. Hyperbaric oxygen: does it promote growth or recurrence of malignancy?Undersea Hyperb Med. 2003;30:1-18.
83.
FeldmeierJJHeimbachRDDavoltDABrakoraMJSheffieldPJPorterAT. Does hyperbaric oxygen have a cancer-causing or -promoting effect? A review of the pertinent literature. Undersea Hyperb Med. 1994;21:467-475.
84.
HafftyBGHurleyRAPetersLG. Carcinoma of the larynx treated with hypofractionated radiation and hyperbaric oxygen: long-term tumor control and complications. Int J Radiat Oncol Biol Phys. 1999;45:13-20.
85.
HenkJMKunklerPBSmithCW. Radiotherapy and hyperbaric oxygen in head and neck cancer. Final report of first controlled clinical trial. Lancet. 1977;2:101-103.
86.
DenhamJWYeohEKWittwerGWardGGAhmadASHarveyND. Radiation therapy in hyperbaric oxygen for head and neck cancer at Royal Adelaide Hospital—1964 to 1980. Int J Radiat Oncol Biol Phys. 1987;13:201-208.
87.
KochWM. Head and neck surgery in the era of organ preservation therapy. Semin Oncol. 2000;27:5-12.
88.
YiotakisJStavroulakiPNikolopoulosT. Partial laryngectomy after irradiation failure. Otolaryngol Head Neck Surg. 2003;128:200-209.
89.
HolsingerFCFunkERobertsDBDiazEMJr.Conservation laryngeal surgery versus total laryngectomy for radiation failure in laryngeal cancer. Head Neck. 2006;28:779-784.
90.
SewnaikAMeeuwisCAvan der KwastTHKerrebijnJD. Partial laryngectomy for recurrent glottic carcinoma after radiotherapy. Head Neck. 2005;27:101-107.
91.
QuerMLeonXOrusCVenegasPLopezMBurguesJ. Endoscopic laser surgery in the treatment of radiation failure of early laryngeal carcinoma. Head Neck. 2000;22:520-523.
92.
MotamedMLaccourreyeOBradleyPJ. Salvage conservation laryngeal surgery after irradiation failure for early laryngeal cancer. Laryngoscope. 2006;116:451-455.
93.
SteinerWVogtPAmbroschPKronM. Transoral carbon dioxide laser microsurgery for recurrent glottic carcinoma after radiotherapy. Head Neck. 2004;26:477-484.
94.
GrantDGSalassaJRHinniMLPearsonBWHaydenREPerryWC. Transoral laser microsurgery for recurrent laryngeal and pharyngeal cancer. Otolaryngol Head Neck Surg. 2008;138:606-613.
95.
PiazzaCPerettiGCattaneoAGarrubbaFDe ZinisLONicolaiP. Salvage surgery after radiotherapy for laryngeal cancer: from endoscopic resections to open-neck partial and total laryngectomies. Arch Otolaryngol Head Neck Surg. 2007;133:1037-1043.
96.
BalmAJHilgersFJBarisGKeusRB. Pectoralis major muscle transposition: an adjunct to laryngeal preservation in severe chondroradionecrosis. J Laryngol Otol. 1993;107:748-751.
97.
DrafW. [Problems of laryngeal reconstruction following perichondritis of the larynx]. HNO. 1980;28:218-221.
98.
MachtayMMoughanJTrottiA. Factors associated with severe late toxicity after concurrent chemoradiation for locally advanced head and neck cancer: an RTOG analysis. J Clin Oncol. 2008;26:3582-3589.
99.
PlatteauxNDirixPDejaegerENuytsS. Dysphagia in head and neck cancer patients treated with chemoradiotherapy. Dysphagia. 2010;25:139-152.
100.
TomitaTTanakaKShindenSOgawaK. Tracheoesophageal diversion versus total laryngectomy for intractable aspiration. J Laryngol Otol. 2004;118:15-18.
101.
TakanoYSugaMSakamotoOSatoKSamejimaYAndoM. Satisfaction of patients treated surgically for intractable aspiration. Chest. 1999;116:1251-1256.
102.
FrancisDOBluminJMeratiA. Reducing fistula rates following laryngotracheal separation. Ann Otol Rhinol Laryngol. 2012;121:151-155.
103.
WeberRSBerkeyBAForastiereA. Outcome of salvage total laryngectomy following organ preservation therapy: the Radiation Therapy Oncology Group trial 91-11. Arch Otolaryngol Head Neck Surg. 2003;129:44-49.
