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OsteoradionecrosisDefinition – Exposure of bone within the radiationtreatment volume of 2-6 months duration or longer
Pathogenesis – 3 HypothesesMeyer (1970) v Irradiated bone subjected to a traumatic event could lead to a superimposed infection similar to osteomyelitisMarx (1983) v 3H theory of ORN. Following radiation, formulation of hypoxic- hypocellular-hypovascular tissue (3H) then tissue breakdown, and finally a nonhealing wound as ORNDelanian and Lefaix (2004) v ORN is due to the activation and dysregulation of fibroblastic activity. A cascade of cytokines and free radicals leads to the destruction of endothelial cells and vascular thrombosis, which leads to necrosis of micro-vessels, local ischemia and tissue loss. The combination of death of osteoblasts, failure of osteoblasts to repopulate, continued osteoclastic activity and excessive proliferation of myofibroblasts, results in bone matrix being replaced by fibrous tissues.
Staging SystemSchwartz and Kagan (2002) v Stage I – Superficial involvement of the mandible with minimal soft tissue ulceration: only the exposed cortical bone is necrotic v Stage II – Both the exposed cortical bone and the underlying medullary bone are necrotic v Stage III – Full diffuse involvement of the mandible, including a full thickness segment of bone.
Osteoradionecrosis - Sequellae Why is this such an important sequellae of radiation therapy?Because advanced cases may lead to fistulaformation as is seen in this patient . . . .
Osteoradionecrosis - Sequellaeprolonged exposures of bone intra-orally,pathologic fractures of the mandible and . . .
Osteoradionecrosis - Sequellae. . . mandibular discontinuity defects with accompanying mandibular deviation, disruption of speech, mastication and saliva control, and facial deformity.
Osteoradionecrosis – Key FactsPrinciple cause – Loss of vasculature v Severe narrowing of the lumens of the facial and inferior alveolar arteries v Loss of the fine vasculature of the bone marrow and the Haversian systems of lamellar bone v Bone matrix replaced by fibrous tissues.Affects the mandible to a much greater degree than the maxilla v More than 90% of all osteoradionecrosis arise in the mandible v Most osteoradionecrosis (ORN) arising from the maxilla heals with conservative treatment and does not require hyperbaric oxygen. Exceptions – ORN’s secondary to chemoRT or Neutron beam therapy.
Osteoradionecrosis - Key FactsThe incidence varies depending on total dosage, clinical tumorvolume, fractionation, modality and dental disease factorv As low as 3% (Beumer et al, 1972) and as high as 37% (Grant and Fletcher, 1966) when high energy photons are usedv Higher when brachytherapy is usedv Extremely high when neutron radiation therapy is used (NRT) (Marunick 2000)v Fewer than 5% of all osteoradionecrosis occurs in edentulous patients (Beumer et al, 1984).v Increased risk associated with concomitant chemotherapy (Kuhnt et al, 2006; Hehr et al, 2006)
Osteoradionecrosis - Contributing Factors High Energy Photons v CRT and Radiation fields – If external beam is used alone, the more the body of the mandible in the field the greater the risk of osteoradionecrosis (ORN). v IMRT may decrease the risk v Dose to Bone – Below 6500 cGy or equivalent the risk is very low and almost all that develop in this dosage range heal with conservative measures and do not require hyperbaric oxygen therapy. v ChemoRT - Increases the risk of ORN and treatment is less predictable.
Changing methods of radiation deliveryConventional radiation therapy (CRT) l 200 cGy per fraction l Total doses l 7000 cGy definitive dose l 5000-6000 cGy post op Intensity modulated radiation therapy (IMRT) This technique uses multiple radiation beams of non-uniform intensities. The beams are modulated to the required intensity maps for delivering highly conformal doses of radiation to the treatment targets, while limiting dose to structures adjacent
Osteoradionecrosis - Contributing Factors High Energy PhotonsIMRT - Volume of the mandible receiving doses in excess of 6500 cGy is reduced
Osteoradionecrosis - Contributing Factors High Energy Photons with CRTDose to bonev 6500-7000 cGy – rate of bone necrosis is 5-15%v 7000-7500 cGy – rate of bone necrosis is 15-50%v 7500 and above - rate of bone necrosis is > 50% Will these numbers hold with IMRT?
Osteoradionecrosis - Contributing Chemotherapy increases the risk!!! vA full course of concomitant chemotherapy increases the Biologic equivalent dose (BED) by 700-1000 cGy*If the patient received concomitant chemotherapy,a serious bone necrosis leading to resection of themandible can occur at doses as low as 5000 cGy.
Osteoradionecrosis - Contributing Factors Modality – Brachytherapy External beam vs combined external beam and brachytherapy. When the dose is boosted locally with brachytherapy with multiple sources positioned close to or on the mandible, the dose to bone locally can be quite high and the patient is at great risk of developing an ORN. *When the dose to the local bone exceeds 7500 cGy, the risk of osteoradionecrosis is 50% or more.
Incidence of Osteoradionecrosis According to Radiation Dose to Bone Incidence of bone necrosisDose to bone (cGy) Dentulous Pts Edentulous<6500 0/36 (0%) 0/3 (0%)6500-7500 8/29 (28%) 1/15 (7%)7500 11/13 (85%) 2/4 (50%)Total 19/78 (24%) 3/22 (14%) Source: Morrish et al, Cancer 47, l980
OsteoradionecrosisPredisposing and precipitating factors 1960’s - 2000 1. Postradiation extraction of teeth within the radiation field* 2. Spontaneous associated with dental infection 3. Preradiation extractions 4. Spontaneous: Dose delivered beyond tolerance of normal tissues 5. Denture irritation 6. Placement of osseointegrated implants into irradiated bone *Most common factors until chemoRT
OsteoradionecrosisPredisposing and precipitating factors since 2000 1. Spontaneous associated with dental infection* 2. Spontaneous: Dose delivered beyond tolerance of normal tissues 3. Preradiation extractions 4. Postradiation extraction of teeth within the radiation field 5. Denture irritation 6. Placement of osseointegrated implants into irradiated bone *Most common factors since chemoRT
Osteoradionecrosis – predisposing factors (cont’d)Postradiation extraction of teeth within the radiation treatment volume-Maxilla In most patients, maxillary teeth in the radiation field can be extracted post radiation, with little risk of osteoradionecrosis. Even if an ORN develops as shown here, the nonvital areas of bone sequestrate naturally, leaving only small local bony deformities.
Osteoradionecrosis – predisposing factors (cont’d)Postradiation extraction of teeth within the radiation treatment volume-Maxilla Both these osteos developed following extraction of teeth after radiation therapy. Both patients received in excess of 6600 cGy to the extraction sites. Conservative treatment was employed (local irrigation, removal of loose sequestra of bone etc.) and both healed several months after onset.
Osteoradionecrosis – predisposing factors (cont’d) Postradiation extraction of teeth within the radiation treatment volume-MaxillaExceptions:v Patients treated with concomitant chemotherapyv Patients treated with neutron radiation therapy (NRT) ORN’s associated with these treatment modalities are frequently intractable and do not respond to any form of treatment including HBO.
Osteoradionecrosis-predisposing factorsPostradiation extraction of teeth within the radiation treatment volume-MandiblePost radiation extraction ofmandibular teeth in the field ofradiation when the patient receivesin excess of 6500 cGy is risky andoften leads to osteoradionecrosis.
Osteoradionecrosis-predisposing factorsPostradiation extraction of teeth within the radiation treatment volume-MandibleAll four of these patients presented with squamouscarcinomas of either the oral tongue or floor of themouth and were treated with external beam photonsand opposed mandibular fields. All received in excessof 6600 cGy and developed ORN after postradiationextractions.All patients developed ORN before the introduction of hyperbaric oxygen andall eventually had major portions of their mandibles resected resulting indiscontinuity defects in order to control the infection.
Postradiation extractions*Ill advised in the mandible if the dose to bone is above 5500 cGy unless accompanied by HBO or the pentoxyfilline-tocopherol protocol Incidence of osteoradionecrosis secondary to postradiation extractions Patients Osteos Grant and Fletcher, 1966 16 7 44% Beumer et al, 1984 40 11 28% Morrish et al, 1980 18 11 61% Marx, et al, 1984 37 11 30% Totals 111 40 36% *In these clinical reports the dose to bone was in excess of 6500 cGy and the patients did not receive HBO.
Osteoradionecrosis – Predisposing factorsPreradiation extraction of teeth within theradiation treatment volumeA In contrast, most ORN secondary to preradiation extraction, such as these, heal with conservative B measures.Most are confined within the attached gingiva(Stage I) and the gingival fibers help maintain theattachment of the periosteum to underlying bone,providing blood supply to the underlying bone andpreventing expansion of the bone exposure.
Osteoradionecrosis – Predisposing factorsPreradiation extraction of teeth within theradiation treatment volume Both patients shownA developed ORN at preradiation extraction sites. Both had been treated with external beam photons and the extraction sites had received in excess of 7100 cGy. B BMost ORN that develops at preradiationextraction sites stays localized withinthe zone of attached tissue and can betreated successfully with conservativemeasures (patient B). Resolution of this ORN took 8 months.
Preradiation extractions Number of patients 120 Osteoradionecrosis directly associated with extraction sites 12Only one of the 12 patients developing ORN associatedwith preradiation extractions required mandibularresection and developed a discontinuity defect of themandible. From Beumer et al, 1984
Osteoradionecrosis – predisposing factors Spontaneous associated with acute periodontal infections All five of these patients presented with similar histories- bone exposure sites treated in excess of 6600 cGy, previoushistory of pain and swelling, followed by a foul smellingdischarge, with eventual pain relief accompanied byexposure of bone.
Spontaneous associated with acute periodontal infectionsv Osteoradionecrosis of the mandible that develops as aresult of periodontal infections after radiation therapy is mostserious (particularly if the Radiotherapy was delivered withexternal beam) because many result in discontinuity defects.v Upon initial presentation most ORN developing in this wayextends deep within the body of the mandible (Stage II or III),and often the lingual or buccal periosteum is dissected awayas the bone exposure enlarges.The periosteum is the prime source of blood supply and its lossresults in divitalization of the underlying bone, leading in mostpatients, to surgical resection of a portion of the mandibular body.
Osteoradionecrosis – predisposing factors Secondary to denture irritation A B Most ORN secondary to denture irritation is not serious as long as it is confined to the residual attached gingiva (Stage I)(A), and heal with conservative measures.
Osteoradionecrosis – predisposing factors Secondary to denture irritation A B Both these ORN’s developed in association with denture wear. In patient “A” the bone exposure developed 7 months after insertion at the site of a preradiation dental extraction and was probably caused by a particle of food becoming lodged beneath the denture. In patient “B” the probable cause was an overextended denture flange. Both patients received over 6900 cGy via external beam but both healed with conservative measures and did not require hyperbaric oxygen.
Osteoradionecrosis – predisposing factors Spontaneous – Dose delivered beyond normal tissue toleranceBoth these patients were treated with a combination ofexternal beam photons and brachytherapy and developedORN adjacent to the sites of placement of iridium implants.Both received over 8500 cGy to the lingual surface of themandible.
Osteoradionecrosis – predisposing factors Spontaneous – Dose delivered beyond normal tissue toleranceBoth these patients were treated with concomitantchemoradiation and the BED (biologic equivalent dose) to theposterior body of the mandible approached 8000 cGy
Osteoradionecrosis – predisposing factors Spontaneous – Dose delivered beyond normal tissue toleranceThis patient was treated with concomitant chemoradiation andthe BED (biologic equivalent dose) to the maxilla approached8000 cGy. Eventually the entire maxilla was lost.
Osteoradionecrosis – predisposing factors Osseointegrated implantsOnly a limited number of anectodal case reportsare available for review. The inicidence willprobably be similar to that seen in patientsundergoing post radiation extraction.
Osteoradionecrosis – predisposing factorsOsseointegrated implants v This patient received 6600 cGy via opposed mandibular fields for a squamous carcinoma of the oral tongue. Implants were placed 6 years after completion of therapy. v Three years after placement the patient developed an infection on the lingual side of the left posterior implant (arrow). Eventually an oral cutaneous fistula developed followed by a pathologic fracture of the mandible. The mandible was resected and reconstructed with a fibula free flap.
OsteoradionecrosisGoal of treatment – Resolution with maintenance of mandibular continuity
Osteoradionecrosis –Treatment Optionsv Conservative – Local irrigation, regular followup, removal of loose sequestra and debridement as appropriatev Hyperbaric oxygen protocol - HBO combined with surgical debridement or resectionv Pentoxifylline – tocopherol protocol Stage I If the ORN is confined within the zone of attached gingiva and not directly associated with the dentition, conservative measures are recommended.
Osteoradionecrosis –Treatment Optionsv Conservative – Local irrigation, regular followup, removal of loose sequestra and debridement as appropriatev Hyperbaric oxygen (HBO) combined with surgical debridement, resection and closurev Pentoxyfilline – tocopherol protocolStage II and IIIDoes the exposure extendbeyond the mucogingivaljunction? Is there evidence ofbone resorption along the inferiorborder of the mandible? If so,either the HBO protocol orpentoxifylline tocophoral protocolshould be considered .
Osteoradionecrosis –Treatment Optionsv Conservative – Local irrigation, regular followup, removal of loose sequestra and debridement as appropriatev Hyperbaric oxygen (HBO) combined with surgical debridement, resection and closurev Pentoxyfilline – tocopherol protocolWhat has been its clinical course? Is the exposure getting worse?If so, either the HBO protocol or the pentoxifylline tocophoralprotocol should be considered . Initial presentation 3 moths later
Osteoradionecrosis –Treatment Optionsv Conservative – Local irrigation, regular followup, removal of loose sequestra and debridement as appropriatev Hyperbaric oxygen (HBO) combined with surgical debridement, resection and closurev Pentoxyfilline – tocopherol protocol What was the mode of therapy? If the dose to the primary was boosted with brachytherapy, what was the dosimetry of the implant. vIf unfavorable, either the HBO protocol or pentoxifylline protocol should be considered. vIf favorable and the external beam dose was below 5500 cGy, conservative therapy can be used.
Osteoradionecrosis –Treatment Optionsv Conservative – Local irrigation, regular followup, removal of loose sequestra and debridement as appropriatev Hyperbaric oxygen (HBO) combined with surgical debridement, resection and closurev Pentoxyfilline – tocopherol protocolvRadical neck on the side of the ORN, continued alcohol andtobacco abuse etc? These factors would encourage the use ofthe HBO protocol or the pentoxifylline-tocopherol protocol.vIf adjunctive or concomitant chemotherapy is used incombination with radiation, the HBO protocol or thepentoxifylline-tocopherol protocol should be considered.
OsteoradionecrosisPredictors of treatment outcomes v Initial presentation v Stage I - Does the ORN extend beyond or is it within the zone of keratinized attached mucosa? v This is an important prognostic factor because, in general, ORN that extends beyond this zone has a poor treatment outcome.
OsteoradionecrosisPredictors of treatment outcomes v Initial Presentation and precipitating factors- Osteoradionecrosis that is precipitated by: v Postradiation extractions – Generally extend beyond the zone of attached keratinized mucosa and extend into the underlying medulary bone. These by definition would be Stage II v Periodontal infections – Generally extend beyond this zone. Most would be Stage II These initiating factors generally imply a poor outcome
OsteoradionecrosisPredictors of treatment outcomes vInitial Presentation and precipitating factors- Osteoradionecrosis that is precipitated by: vPreradiation extractions – Generally stay within this zone. Most are Stage I vDenture irritation – Generally stay within this zone. Most are Stage I.These initiating factors generally imply a good outcome
OsteoradionecrosisPredictors of treatment outcomes vMode of radiation treatment vCombined external beam and brachytherapy: Generally such ORN is locally confined and heals with conservative therapy if the dosimetry of brachytherapy is favorable. v External beam alone: If the ORN occurs in the mandible in a high dose area the outcomes are less favorable. vConcomitant chemoRT: ORN’s in these patients generally do not respond to conservative measures, HBO or the pentoxyfilline – tocopherol protocols and require resection and reconstruction with a free flap
OsteoradionecrosisGoal of treatment – Resolution with maintenance of mandibular continuityPredictors of treatment outcomes vDose and Treatment Volume vThe higher the dose and the larger the treatment volume the less predictable the outcome.
Osteoradionecrosis-TreatmentORN extending beyond the mucogingival junction as is seen in these two patients• When it does so, and the radiation is delivered via external beam, HBO should be considered. vIs there evidence of bone resorption associated with trabecular bone or the inferior border of the mandible as seen here? vIf so, HBO should be considered.
Osteoradionecrosis-TreatmentORN extending beyond the mucogingival junction as is seen in these two patients• When it does so, and the radiation is delivered via external beam, HBO should be considered.
Osteoradionecrosis-Treatment Decisions and Clinical ExamplesIs there evidence of bone resorption associatedwith trabecular bone or the inferior border of themandible as seen here?If so, HBO should be considered.Eventually patient suffered a pathologic fracture of the mandible.
Osteoradionecrosis-Treatment DecisionsClinical course - Has the bone exposure enlarged to extend beyond the mucogingival junction?• If so, HBO should be considered. Initial presentation 3 months later
Osteoradionecrosis-Treatment DecisionsBrachytherapy, tumor dose and the dose to the local bone - What was the dosimetry of the implant? If the dosimetry associated with the implant is favorable, i.e., the total dose to the inferior border and the buccal plate is below 5500 cGy, conservative measures are recommended even if the ORN extends beyond the mucogingival junction.
Post-radiation dental diseasePost radiation extractionsand HBOl Dose to Mandible is greater than 5500 cGyl Expensive and time-consuming
Treatment of Osteoradionecrosis - SummaryRole of Conservative Therapy v ORN confined within the zone of attached keratinized mucosa that is stable or improving. v ORN in patients treated with brachytherapy with favorable dose distribution. v Initial treatment for an ORN when the dose to bone is below 6500 cGy and delivered with external beam and conventional fractionation.
Treatment of Osteoradionecrosis - SummaryRole of Hyperbaric oxygen v ORN that extends beyond the mucogingival junction in patients treated solely with external beam therapy where the dose to bone is in excess of 6500 cGy using conventional fractionation. v ORN precipitated by periodontal or periapical infections when the patient has been treated with high dose external beam therapy. v ORN associated with brachytherapy that extends beyond the mucogingival junction that does not respond to conservative therapy and where the dosimetry associated with the implant is unfavorable. v ORN resulting in significant resorption of bone extending to the inferior border of the mandible.
Osteoradionecrosis-Treatment DecisionsOther factors to consider* v Radical neck dissection on the side of the ORN. The facial artery, which supplies feeding vessels to the lingual periosteum, is removed during this procedure. v Continued alcohol and tobacco abuse v Poor oral compliance*Thesefactors would favor the use of theHBO or pentoxyfilline-tocopherol protocols.
OsteoradionecrosisRole of surgical debridement v Incombination with HBO or the pentoxifylline - tocopherol protocolRole of surgical resection and reconstruction v When conservative therapies have failed v When patient presents with history of high dose radiation in combination with concomitant chemotherapy
Osteoradionecrosis – Role of Conservative Therapy Clinical Examples This patient was S/P 5500 cGy delivered with external beam plus 2500-3500 cGy via an iridium implant for a squamous carcinoma of the right lateral tongue and floor of the mouth. Two years later he developed an ORN on the lingual surface of the mandible. Evaluation of the dosimetry of the implant revealed most of the treatment volume confined to the lingual surface of the mandible Exam revealed the ORN to be undermined by the oral epithelium and loose. Removal was accomplished with cotton pliers revealing normal epithelium beneath. Eventually all the teeth exfoliated and the remaining bone exposures sequestrated spontaneously.
Osteoradionecrosis-Role of Conservative Therapy Clinical ExamplesThis patient received 5500 cGy with external beam with thelinear accelerator plus 2500-3500 cGy via an iridium implant.Two years later he developed an ORN on the left lingual surfaceof the mandible. Nonvital bone was removed with a high speed air rotor with copius irrigation. After several episodes mucosal coverage was attained.Close examinationreveals that thebone exposure wasbeing underminedby oral epithelium.
Exception High Dose Rate Implantsl Technique sensitive l It is very easy to deliver excessive doses when using this technique
Osteoradionecrosis-Role of Conservative Therapy Clinical Examples• This patient is S/P 7100 cGy with external beam photons for treatment of a squamous carcinoma of the soft palate. Opposed lateral facial fields were employed.• Six months after therapy he developed an ORN at the site of a preradiation extraction.• The ORN was confined to the attached gingiva. After 8 months of conservative therapy the ORN had resolved.
Osteoradionecrosis – Treatment with HBO Clinical Examples • ORN associated with external beam • If the ORN extends beyond the mucogingival junction and the dose to bone is above 6500cGy (with conventional fractionation) or its biological equivalent, hyperbaric oxygen combined with surgical sequestrectomy is recommended.
Osteoradionecrosis – Treatment with HBO Clinical ExamplesThis patient presented S/P 7100 cGy delivered with externalbeam for a squamous carcinoma,with an ORN of the right lingualsurface of the mandible. Note that the exposure extends beyondthe mucogingival junction. Following a course of hyperbaric oxygen (30 treatments), surgical excision of the nonvital bone and extraction of teeth in the local area was accomplished. Another ten HBO treatments were administered. The wound re-epithelialized and mandibular continuity was maintained.
Osteoradionecrosis-Treatment with HBO Clinical Examples l This patient presented with a bone exposure after therapy at a preradiation extraction site. He had received over 9500 cGy to the right body of the mandible. He continued to smoke and drink heavily. The necrosis continued to The exposure began to enlarge and eventually the enlarge and so the patient entire body of the mandible was referred for a course of was resected and later HBO. reconstructed.HBO is effective when the tissues are still viable but delay inthe face of high dosage may compromise the chance ofsuccess and result in greater bone loss.
Osteoradionecrosis-Treatment with HBO Clinical Examples This patient presented with a small ORN on the lingual of #29 and #30 secondary to a periodontal abscess. Four years earlier she had received 5500 cGy with external beam plus another 4500 cGy via an iridium implant. Note the bone loss associated with these teethHygiene was excellent andthe patient had ceasedusing tobacco or alcohol.Note that the labial gingivaappears quite healthy.
Osteoradionecrosis – Treatment with HBO Clinical Examples Conservative therapy was initiated but the ORN increased in size.•HBO combined with surgical debridement was recommendedbut the patient refused. The exposure progressed until thelingual plate from molar to molar was exposed and the patientdeveloped an orocutaneous fistula.•The patient finally accepted HBO and a series oftreatments were initiated combined with biweekly irrigationsand debridement.
Osteoradionecrosis-Treatment with HBO Eventually a large segment of nonvital bone was undermined by oral epithelium, became loose and was removed with cotton pliers. The oral cutaneous fistula closed. Appearing beneath, was a bed of granulation tissue and oral mucous membrane. However, small localized areas of exposed bone still remained.
Osteoradionecrosis - Treatment with HBO l One month later most of the granulation tissue had been covered with oral epithelium During the next 18 months the small residual areas of exposed bone became undermined by oral epithelium and sequestrated sometimes helped along with a high speed air rotor. Three years later most of the teeth had exfoliated and thepatient was fitted with a removable partial denture.
Eventually all the mandibular teeth exfoliated. Note thetelangiectasia associated with oral mucosa and the atrophy ofthe tongue. A complete denture was fabricated for thepurposes of lip support and esthetics and well tolerated by thepatient.
Why was the outcome successful?•The dosimetry of the implant was favorable.Although the implant delivered a high dose to alarge volume of tissue, the dose to the inferiorborder and buccal cortical bone of the mandiblewas low (only slightly above 5500 cGy)•The external beam dose was low – 5500 cGy. At this level theperiosteum and marrow retain significant vascular elements.•The patient was compliant. The patientstopped smoking and her oral hygiene wassuperb. She never missed an irrigationappointment. Hyperbaric oxygen. Thesetreatments revascularized themarginally necrotic tissues andfacilitated the patient’s response tothe local infections.
Osteoradionecrosis –Treatment with Surgical This patient developed an ORN following postradiation extractions. He had received 6600 cGy for a squamous carcinoma of the right lateral tongue. However, a localtreatment was initiatated Conservative surgical sequestrectomy was attempted which resulted in the stable and the bone exposure remained exposure extending beyond the zone of and began to improve. attached gingiva. The exposure rapidly expanded, eventually extending lingually to the inferior border of the mandible. Pathologic fracture and an orocutaneous fistula soon followed and the mandibular body was eventually resected inClinical Examples order to resolve the infections.
Why was the outcome so unsuccessful?• The patient continued to smoke and use alcohol.• All the radiation was delivered with external beam photons. The tumor dose was 6600 cGy and the dose was distributed homogenously from the buccal side to the lingual side of the mandibular body.• At these dosage levels the vascularity and cellularity of the periosteum was severely compromised and no longer provided sufficient vascular support to the underlying bone. However, as long as the periosteum remained attached to underlying bone, the bone remained viable.• When the mucoperiosteum was dissected away
Why was the outcome so unsuccessful?• As long as the exposure was confined within the attached mucosa, it did not spread because the gingival fibers helped to maintain contact between the periosteum and cortical bone.• Once the exposure had spread beyond the attached mucosa, the attachment of periosteum to the underlying bone became very tenuous. The slightest infectious insult will dissect the atrophied periosteum from the underlying bone. When dissection occurs, the bone looses its primary remaining blood supply and becomes essentially nonvital. HBO will not salvage such a mandible and its resection is inevitable.
Osteoradionecrosis – Case reportl This patient presented with an ORN 18 months post radiation. It is not painful, there are no draining fistulas and a panorex reveals little change in the density of the trabecular bone or the cortex of the inferior border of the mandible. The exposure has been present for about 3 months and extends beyond the mucogingival junction lingually. What radiation data do you need to acquire before developing a plan of treatment? Mode of therapy Dose to bone Dosimetry What patient data do you need to obtain? Oral Compliance Smoking habits Medical history
Osteoradionecrosis – Case reportl The patient received 5000 cGy to the tumor volume and the neck with external beam high energy photons. The dose to the primary was boosted with an iridium implant with an additional 2500-3500 cGy. The CT generated dosimetry is shown here. What treatment do you recommend? Conservative therapy was employed. Bone undermined by oral mucosa, was periodically removed with a high speed air rotor. Within 9 months the nonvital bone had been removed and mucosal integrity was restored.
Osteoradionecrosis - Case report l This patient was treated with external beam high energy photons and brachytherapy for a squamous carcinoma of the right lateral tongue. Two years after completion she developed an acute periodontal infection which eventually led to dehiscence of the lingual gingiva and an osteoradionecrosis. What information do you need to develop a plan of treatment for this patient?Radiation data • Fields of external beam • Dosimetry of the implant • Dose to bone of the buccal half of the mandibleOther data Oral compliance Smoking habits Updated MH
Osteoradionecrosis – Case Report• Dosimetry was very favorable. Since the implants had been placed into the lateral border of the tongue, the dose delivered to the middle of the mandibular body by the implant was minimal.• The dosage delivered to lingual plate was about 2000 cGy.• Oral hygiene was poor, however, and the patient continued to use tobacco.What treatment would you recommend for this patient?
Osteoradionecrosis-Case Report Conservative therapy was adopted because the external beam dose to the mandible was low and the dosimetry of the implant was favorable.The premolar and the cuspid exfoliated and thenonvital bone sequestrated within 9 months.Eventually all of the remaining teeth exfoliated.
Osteoradionecrosis – Surgical Management Free vascularized flaps and myocutaneous flaps can be used to cover exposed areas of bone following surgical sequestrectomy.The nonvital bone is removed surgically and a flapis used to cover the remaining bone. In this patienta pectoralis myocutaneous flap was used.
Osteoradionecrosis – Surgical Management Reconstruction with fibula free flapsPotential problems with free flap reconstructionvSemi-occluded vessels in the neck with fibrotic and fragile walls.vComplication rate -50% Suh et al, 2010vRelapse rate about 25 %
Osteoradionecrosis: Treatment PhilosophiesMarx • Dr. Marx and his colleagues believe almost all osteoradionecrosis of the mandible would benefit from hyperbaric oxygen treatment. • What follows is the protocol developed by Dr. Marx used to treat patients with osteoradionecrosis.
Hyperbaric Oxygen (per Marx) • Stage I – These patients present with ORN but without pathologic fracture of the mandible, orocutaneous fistula or radiographic evidence of bone resorption of the inferior border of the mandible. • Thirty HBO treatments (2.4 atmospheres, 100% oxygen for 90 minutes) • At the end of 30 treatments, if improvement is noted, another 10 treatments are administered.If no improvement is noted, the patient is considereda nonresponder and is advanced to Stage II.
Hyperbaric Oxygen (per Marx) • Stage II • Nonresponders are taken to surgery and surgical debridement of the local area is performed. Nonvital bone is removed via a transalveolar sequestrectomy and the labial and lingual mucoperiosteal flaps are closed in three layers over a base of bleeding bone. • An additional 10 HBO treatments are added.If the wound dehisces, the patient is considereda nonresponder and advanced to Stage III.
Hyperbaric Oxygen (per Marx)• Stage III • Nonresponders from Stage II therapy, and patients presenting with orocutaneous fistula, pathologic fracture of the mandible or bone resorption of the inferior border of the mandible, are considered Stage III patients. • Following the initial 30 treatments, bony segments of the nonvital mandibular bone are resected. Soft tissue deficits if present are restored with local or distant flaps and orocutaneous fistulas are closed • Another 10 HBO treatments are administered and the patient is advanced to Stage IIIR
Hyperbaric Oxygen (per Marx)• Stage IIIR • Ten weeks after resection the mandible is reconstructed with a free bone graft, using a transcutaneous exposure. • Mandibular fixation is achieved and the patient given another 10 HBO treatments.
Hyperbaric Oxygenl Permanence l Patients restudied 4 years after HBO demonstrated the same angiogenesis as those studied immediately after completion. l New hyperbaric induced vessels do not appear to involute after cessation of HBO faster than the normal rate of aging.
Osteoradionecrosis: Reconstruction after Resection v Free grafts vs free vascularized graftsBoth methods achieve successful results in the hands ofexperienced surgeons although the success rates associated withthe use of free grafts is enhanced by the use of hyperbaricoxygen.Potential problems with free flaps:v Semi-occluded vessels in the neck with fibrotic and fragile walls.vRelapse
Osteoradionecrosis: Reconstruction after ResectionPatient is S/P resection of the mandible for an ORN. He hadreceived in excess of 6800 cGy to the body of the mandible withexternal beam. The defect was restored with a block bone graft from the iliac crestHyperbaricoxygen wasunsuccessful insaving thecontinuity of themandible. One year S/P bone graft
Osteoradionecrosis: Reconstruction after ResectionPatient is S/P resection of the mandible for an osteoradionecrosis.He had received in excess of 6800 cGy to the body of themandible. The defect was restored with a block bone graft from the iliac crestSix months laterosseointegratedimplants weresuccessfullyplaced into thegrafted bone. One year S/P bone graft
Osteoradionecrosis – PreventionSince Osteoradionecrosis (ORN) is a process thatprimarily affects the mandible . . . . . andsince mandibular teeth are the prime precipitatorsof ORN we recommend the following strategies.Prevention strategies Remove mandibular teeth with significant periodontal or advanced caries in the field prior to therapy in high dose areas. Remove mandibular teeth adjacent to a prospective iridium implant.
Osteoradionecrosis – PreventionSince Osteoradionecrosis (ORN) is a process thatprimarily affects the mandible and . . . . .since mandibular teeth are the prime precipitatorsof ORN we recommend the following strategies.Prevention strategies Remove all teeth within the gross tumor volume and the patient is potentially noncompliant particularly in patients who receive concomitant chemotherapy.
Soft Tissue NecrosisDefinition – A non-neoplastic mucosal ulcerationoccurring in the postradiation field and which does notexpose bone Most occur within a year of therapy and develop at the site of radioactive implants or peroral cone application sites.The key issue is to determine whether these ulcerations represent recurrent tumor. Clinical symptoms useful in making the diagnosis are:a) Soft tissue necroses lack an inflammatory halob) Soft tissue necrosis is much more painful than tumor recurrencec) Soft tissue necroses are not indurated, tumor recurrences are indurated
Soft Tissue NecrosisTreatment • Establish the diagnosis • Local excision and primary closure • Local supportive measures and followup • Hyperbaric oxygen
Soft Tissue Necrosis Patient received 5500 cGy via external beam and another 2500-3000 cGy with a radium needle implant for a squamous cell carcinoma of the lateral border of the tongue.v Nine months after therapy he developed this ulceration at the site of the tumor.v Cytology and biopsy were negative and a diagnosis of radiation soft tissue necrosis was assumed.v The lesion epithelialized 4 months later
Soft Tissue NecrosisSoft tissue necrosis secondary to chemoradiation The remaining soft palate musculature was scarred and atrophic and elevated poorly. There was little lateral wall movement. The defect at the junction of the hard and soft palate was easily obturated, but not the posterior velopharyngeal defect
Chemoradiationv Late effects of radiation are more profound, i.e. risk of osteoradionecrosis is higher at the lower doses.v Treatment outcomes are less predictable v The usual methods of treatment recommended in this program of instruction based on dosage and initial clinical presentation may not apply and may not be as effective when chemoradiation has been used. v High relapse rate when using free flaps for reconstruction
Neutron Radiation Therapy (NRT)Treatment outcomes are less predictable andthe incidence of ORN is higher• The usual methods of treatment recommended in this program of instruction may not apply and may not be as effective.
Neutron Radiation Therapy (NRT)• Treatment outcomes are less predictable and the incidence of ORN is higher • In a report by Marunick et al (2000), 4 of 9 patients treated for malignant salivary gland tumors arising in the maxilla or the paranasal sinuses, developed osteoradionecrosis. • None responded to the methods of treatment described in this program and eventually lead to loss of the entire palate in most of the patients.
Osteoradionecrosis Secondary to ChemoradiationvSpontaneous – in most instances no known causative factorsvNot responsive to HBO
ORN secondary to ChemoRTl Dramatically higher rates in the maxilla with poorer outcomes.
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