Prosthodontic management of abnormal tooth development secondary to chemoradiotherapy

Neuroblastoma, a cancer of the sympathetic nervous system, is predominantly a tumor of early childhood, with two thirds of the patients younger than 5 years of age. The symptoms relate to the location of the tumor (abdomen, pelvis, neck, and chest) and usually include abdominal pain, swelling, and feelings of fullness caused by the pressure of the tumor, bone pain from metastases, proptosis and periorbital ecchymosis, fever, anemia, hypertension, and diarrhea.  

Treatments include surgery, radiation therapy, chemotherapy, bone marrow transplantation (BMT), and immunotherapy. Early stage treatment of neuroblastoma may involve only surgery to remove the tumor. When the disease is more advanced, surgery, radiation, and chemotherapy are combined. BMT may be used following aggressive chemotherapy and immunotherapy.  

Chemotherapeutic regimens with radiotherapy should balance efficacy with safety and tolerability to maintain or improve survival, function, and quality of life. The mucosal lining of the gastrointestinal tract, including the oral mucosa, is a prime target for treatment-related toxicity by virtue of the rapid cell turnover rate. The oral cavity is highly susceptible to direct and indirect toxic effects of cancer chemotherapy and ionizing radiation, and normal cells as well as tumor cells undergo cell death or necrosis with the results of compromised function and severe complications.

The abnormalities encountered are not limited to but include underdevelopment of the teeth and jaws, complete or partial dental agenesis, root malformation, and hypoplasia of jaws. The effects on tooth development are more significant in children treated before the completion of amelogenesis. If treatment occurs before significant calcification is completed, the tooth bud may be damaged or destroyed. The morphological changes include microdontia, hypodontia, malformed and shortened roots, as well as mandibular hypoplasia. The impaired root development results in reduction of alveolar bone growth and vertical development of the lower third of the face.

The use of dental implants has significantly improved the level of predictability and function in prosthodontic rehabilitation. However, placement of dental implants in growing patients requires additional consideration due to potential dental and skeletal growth; concerns include possible trauma to tooth germs, tooth eruption disorders, and multidimensional restrictions of skeletal craniofacial growth. If implants are placed before the completion of growth, the positional relation of the implants may be altered when growth is completed. The osseointegrated implants will become submerged relative to the adjacent teeth, and surrounding alveolar bone may fail to move occlusally with the adjacent dentition and bone. Implants placed in the maxilla and the posterior region of the mandible may be more at risk because of the vertical and transverse growth of the maxilla and mandible. The growth of the anterior mandible, however, remodels differently. This clinical report describes the prosthodontic management of a patient with severe developmental disturbances in the developing dentition following chemoradiotherapy of a neuroblastoma at the age of 2 years. Osseointegrated implants were used to support and retain the definitive mandibular prosthesis.

Clinical report  

A 12-year-old boy presented to the University of Michigan Hospital Dentistry Clinic, Ann Arbor, Mich, with a chief complaint of dental pain in multiple quadrants when eating ( Fig. 1 ). The medical history revealed that he was diagnosed with a neuroblastoma at age 2. The tumor was extensive (stage IV) and advanced to the left temporal fossa and left orbit with intracranial extension, with metastasis to both femurs bilaterally and a left adrenal mass. Chemotherapy, including a series of intravenous administration of cytoxan, vincristine, cis-platinum, nitrogen mustard, and adriamycin, was initiated for control of the disease when the diagnosis was made. The treatment was completed over approximately 5 months without negative events. Radiation therapy was delivered to the eye and brain areas; external photon beams were directed to the target tissue areas, including 2000 cGy to the left orbit and 1000 cGy to the entire calvarium. This was followed by total body irradiation (TBI) and syngeneic BMT at the Cleveland Clinic, Cleveland, Ohio. Complications which subsequently developed from this transplant included bilateral cataracts, growth retardation, and poor weight gain. The patient underwent growth hormone treatments but experienced a blunted growth hormone response.

Clinical examination revealed a grossly carious maxillary left first molar and mandibular right first molar along with root fragments in the area of the maxillary right first molar (Fig.2 + 3 ) . The mandibular anterior teeth displayed slight mobility and gingival swelling. Radiographic examination revealed carious teeth (maxillary left first molar, mandibular right first molar, and maxillary right first molar), lack of root development for the entire maxillary and mandibular dentition, missing maxillary central incisors, maxillary left lateral incisor and mandibular left central incisor, missing maxillary and mandibular second molar, and second premolars bilaterally. The roots of the mandibular incisors and canines were about one third in length and in width, resulting in significantly compromised tooth support. Multiple missing teeth and failure of teeth to erupt to the occlusal plane resulted in diminished masticatory function. The facial and maxillomandibular structures appeared symmetrical. The lining mucosa and gingiva were healthy without any signs of telangiectasia or tissue atrophy. Moderate inflammation was noted in the mandibular anterior marginal gingiva along with plaque and calculus accumulation. The function of salivary glands appeared normal, with a copious amount of salivary excretion. Mandibular movement was within a normal range, without deviation, and tongue function was normal.

The patient and parents were made aware that the carious teeth were nonrestorable, and the remaining dentition had a poor prognosis due to short root length and lack of bone support. After discussing different treatment modalities, including an overlay removable partial denture, conventional complete dentures, and an implant overdenture, the plan of an immediate maxillary complete denture with no mandibular prosthesis, followed by a definitive complete maxillary denture opposing an implant-retained mandibular overdenture, was selected to preserve mandibular bone, yet allow early use of a maxillary prosthesis for esthetics.

Diagnostic maxillary and mandibular impressions were made with irreversible hydrocolloid (Jeltrate; Dentsply Caulk, Milford, Del) using stock metal trays (Coe Impression Tray; GC America, Alsip, Ill). The impressions were poured in ADA Type III dental stone (Microstone; Whip Mix Corp, Louisville, Ky) for treatment planning.

Maxillomandibular relation records were made and the casts were mounted on an articulator (Hanau Wide-Vue Arcon 183; Waterpik Technologies, Ft. Collins, Colo). Artificial teeth (Bioblend IPN; Dentsply Trubyte, York, Pa) were selected, and the maxillary cast was modified to prepare for immediate denture fabrication. As the intraoral evaluation of the aligned denture teeth was limited due to the malposition of teeth, the midline and lip lines were assessed intraorally and transferred to the casts. The maxillary artificial teeth were arranged to provide esthetics and functional relation with surrounding oral structures. The maxillary denture was processed in heat-polymerizing acrylic resin (Lucitone 199; Dentsply Trubyte).

After obtaining informed consent, all the remaining teeth were extracted and four 2-stage endosseous dental implants (Zimmer Dental, Carlsbad, Calif) were placed immediately in the anterior mandible under general anesthesia. Preoperative antibiotics (Kefzol; Eli Lilly, Indianapolis, Ind) were provided intravenously to reduce bacteremia. The implants, all 3.25 mm in diameter and 13 mm in length, were placed in the following locations: right mandibular first premolar site, right mandibular canine site, left mandibular canine site, and left mandibular second premolar site. The flaps were coronally positioned with sutures to achieve primary closure. A prescription was provided for chlorhexidine gluconate (Zila Inc, Phoenix, Ariz) mouth rinse twice per day, as well as acetaminophen 325 mg with codeine 15 mg (Tylenol with codeine; McNeil Pharmaceutical, Ft. Washington, Pa), 1 tablet every 4 hours as needed for pain control.

A maxillary immediate interim denture was inserted to provide speech function, esthetics, and psychologic comfort. Implant surgery and subsequent healing was uneventful. Second-stage surgery was performed 6 months after the implant placement. The implants were uncovered and transmucosal healing abutments (Zimmer Dental) were connected .

After 3 weeks of soft-tissue healing, the prosthetic phase of treatment was begun. Following placement of 1-piece tapered abutments (Zimmer Dental), a transfer impression was made of the mandibular implants. Impressions of the edentulous maxillary arch were made, using a custom tray, conventional border molding with modeling plastic impression compound (Kerr Corp, Orange, Calif), and polysulfide impression material (Permlastic; Kerr Corp). The impressions were poured in ADA Type V dental stone (Die-Keen; Heraeus Kulzer Inc, Armonk, NY) to generate the definitive casts.

The casts were mounted on an articulator with a face-bow transfer and maxillomandibular relation records. Artificial teeth (Bioblend IPN; Dentsply Trubyte) were arranged and evaluated intraorally to verify dentolabial relation, lip support, and horizontal and vertical jaw relations. A silicone putty index (Lab-Putty; Coltene/Whaledent Inc, Cuyahoga Falls, Ohio) was made to maintain the dimensional relation of the teeth, evaluate interarch space, and guide the development of the mandibular tissue bar. Castable copings (Zimmer Dental) were used to cast an implant-connecting bar using a palladium-based alloy (Option; Dentsply Ceramco, York, Pa) with ball attachments (VKS; Bredent, Senden, Germany). The bar was designed to touch the mucosa of the alveolar ridge passively for hygiene and alignment of artificial teeth . The fit of the bar was evaluated clinically and radiographically with 1 screw tightened into a distal implant site ( Fig. 4 )

 

The silicone index was used to rearrange the artificial teeth in relation to the implant-connecting bar. Metal occlusal surfaces were developed for the mandibular posterior teeth, as the interocclusal space was limited. The superstructure was fabricated in a cobalt-chromium alloy (Vitallium; Dentsply Austenal, York, Pa). The definitive cast was flasked along with the metal superstructure and processed to attach the mandibular anterior artificial teeth to the superstructure, using heat-activated methyl methacrylate (Lucitone 199; Dentsply Trubyte). The buccal surfaces of the mandibular posterior teeth were veneered with a processed composite resin (Sinfony Indirect Lab Composite; 3M ESPE, St. Paul, Minn) buccal veneer (Fig. 5 ).  Intraoral evaluation of the tooth arrangement was performed to verify speech function, esthetics, and the maxillomandibular relationship. The matrix nylon portions of the attachments were placed into the metal superstructure (Fig. 6 ). The processed dentures were finished, polished, and immersed in cold water for hydration for 72 hours before insertion.

 

 

At insertion, pressure indicating paste (PIP; Mizzy Inc, Cherry Hill, NJ) was used to identify interferences on the intaglio surface of the dentures, and the interferences were adjusted. A clinical remount procedure was performed to equilibrate the occlusion and eliminate interferences during excursive movements. The tissue bar was tightened and torqued to 20 Ncm.

Oral hygiene instructions included brushing the denture and denture-bearing mucosa after every meal, along with the use of a conventional toothbrush and an interdental brush (Proxabrush; Butler GUM, Chicago, Ill) to clean around the dental implants and the metal bar. Routine recall appointments were scheduled every 6 months to examine the soft tissue health and stability of the implants and the prosthetic rehabilitation, and to evaluate and replace the nylon retentive matrices. No other modifications have been required. The patient is now 24-years old and reports good function and no discomfort with the prostheses. He does complain of poor retention of the maxillary complete denture prosthesis, which requires the use of denture adhesive. Future treatment will include remaking the maxillary prosthesis, with or without the use of dental implants.

Discussion

The prognosis for patients diagnosed with childhood cancer has improved with the development of multiple therapeutic modalities, including radiation and chemotherapy. Withthe significant increase in the survival rates of these patients, long-term consequences of the therapies, including altered development, are important factors to follow years after the therapy is discontinued. When administered to a growing individual, neither chemotherapeutic agents nor radiation therapy differentiate between tumor cells and normal cells. The failure to distinguish can result in abnormal growth and development, including disturbances in dental and craniofacial structure.

The degree and severity of the disturbances have been reported to relate to age at initiation of treatment, treatment modalities involved, chemotherapeutic protocol, and dose and field of radiation. The patient described in this report began to receive a series of chemotherapy and cranial irradiation at the age of 2, when permanent tooth germs are developing and under active metabolism. Children younger than 6 years of age at diagnosis and initiation of therapy who are long-term survivors of childhood cancer have been found to develop more dental abnormalities.

The effects of chemotherapy alone on root growth are not clear, but include hypomineralization and hypoplasia. Disturbances were found in both enamel and dentin, and distribution of the incremental lines in the enamel corresponded to periods of intensive treatment with vincristine (Oncovin; Eli Lilly), one of the chemotherapeutic agents administered to this patient. Vincristine is an antimicrotubular drug that reduces both the mitogenic and secretory activity in a number of different cell types. Nasman et al reported a relative prevalence of abnormalities in the mandibular teeth. Root abnormalities were found in 94% of children exposed to chemoradiation, as compared with 19% of children treated with chemotherapy only.

Children receiving BMT before the age of 12 and conditioned with TBI of 10 Gy have been reported to develop disturbances in craniofacial and dentoalveolar structures, including tooth agenesis and root abnormalities.7 Histologic changes in both enamel and dentin exhibit numerous incremental lines and gross hypoplasia in the cervical part of crowns, corresponding to the time of administration of 10 Gy of TBI. The mitotic activity of the differentiating cells in the tooth germ makes them radiosensitive, and this, combined with the nonrepopulating nature of these cells, can result in hypoplastic defects. Duggal quantified the impact of TBI on tooth development by measuring the root surface area. The root surface area was much smaller in patients who received BMT and TBI than in those who received chemotherapy alone. Disturbances in root development, such as short, tapered roots, as found in the present patient, indicate that the disturbances are a result of the combined effect of all the cytotoxic drugs given and radiation therapy.

Placement of dental implants in a growing maxilla may restrict transverse growth occurring across the midline suture or create a space problem, depending on the design of the prosthesis. However, the dimension of the mandible increases by vertical/horizontal condylar and ramus growth, along with slight apposition at the chin in the adolescent. The length and width of the anterior mandible reaches its maximum size before the eruption of the deciduous teeth, and the arch width in the premolar region stabilizes after premolar eruption. To accommodate the lowering of the mandibular arch, mandibular incisors and molars erupt and drift vertically. Thus, implants placed in the anterior or posterior mandible can be submerged by appositional growth of the alveolus, and anterior implants can be exposed from labial resorption in the infradental fossa. However, the complications associated with osseointegrated implants would be negligible in the anterior segment of the completely edentulous mandible, as the growth of the bone is expected to be minimal with the loss of teeth and cytotoxity of chemotherapy.

Alveolar bone loss following tooth loss is an ongoing process because of the lack of functional stimulation, and the process continues under removable prostheses throughout an individual's life. Thus, the use of dental implants is considered a reasonable treatment modality to modify the stress distribution mechanism and retard bony resorption in situations of congenital anodontia, dental abnormalities, and the presence of little alveolar bone.

Successful immediate implant placement into a fresh extraction socket further prevents the loss of the residual ridge height and width as well as soft tissue dimensions. The additional benefits are reducing patient morbidity and expense by eliminating additional surgery and more ideal implant positioning for biomechanics and esthetics. Coronal space around implants from the dimensional mismatch with the socket also appears to heal clinically without connective tissue intervention, as implants are stabilized in the bone apically. The long-term success rate reaches 95%, which is comparable with that of the delayed implant placement, with the use of proper selection criteria and reliable techniques. There seems to be a correlation between implant failure and immediate insertion in situations in which periodontitis is a reason for tooth extraction. Infrabony defects and an increased gap between the bone and implant may jeopardize primary stability and offer a negative local influence.

The removable implant-retained mandibular overdentures, which involve the splinting of implants with an implant-connecting bar, have demonstrated clinical success with good long-term results and high patient satisfaction with prosthesis stability, comfort, and masticatory function. The successful treatment outcome has been related to good bone quality, access to oral hygiene for healthy marginal soft tissue and stable marginal bone, and reduced stress along the crest bone. This design, however, requires regular prosthodontic maintenance for attachment replacement as the attachments wear and deform.

With recent significant increases in long-term survival rates of children with malignancies, altered dental development becomes an important factor in the years following the completion of chemoradiotherapy. The changes associated with normal tissue growth and development in these patients may require extensive dental care and impact the patient's quality of life. A quarter of the patients who received chemoradiotherapy have been reported to develop severe cosmetic and/or functional sequelae necessitating surgical and/or orthodontic intervention. Dental evaluation at diagnosis, frequent dental evaluations, an intense oral hygiene program, and long-term radiographic follow-up may help to ensure appropriate preventive measures, minimize dental and periodontal disease, and improve overall dental health. Effective interaction between radiation therapists and medical and dental oncologists may allow prosthodontic rehabilitation to proceed in a predictable manner.

Summary                     

Young adults with abnormal dental development secondary to chemoradiotherapy for childhood malignancy present a treatment challenge. Prosthodontic rehabilitation is often difficult to achieve due to the shortened roots with poor long-term prognosis. The use of osseointegrated implants contributes significantly to the prosthodontic rehabilitation, resulting in improved masticatory performance and comfort. This clinical report presented the prosthodontic management of a patient with dental abnormalties secondary to chemoradiotherapy using osseointegrated implants and an implant connecting bar with a ball attachment system to assist with retention, support, and stability of a mandibular overdenture opposing a maxillary complete denture.

SOURCE : The Journal of Prosthetic Dentistry
Volume 98, Issue 6, December 2007, Pages 429-435