Irradiated patients Patients under biphosphonates Patients under targeted therapy
Regardless of the location and histological type, a patient with cancer will undergo various anti-cancer treatments: chemotherapy, radiotherapy, surgery, new so-called “targeted” therapies, and various associated treatments;
Nowadays, more and more patients with cancer affecting the head or neck, mainly the upper respiratory and digestive tracts, are resorting to radiotherapy to treat their condition.
The advantages of this approach, as opposed to surgery, are that it is less mutilating and causes fewer cosmetic and functional complications.
However, this technique can cause significant side effects that the dentist must take into consideration. Among these, the most important are radiation caries, radiomucositis and osteoradionecrosis.
RADIOTHERAPY
Radiotherapy is a therapeutic modality used in head and neck cancerology, intended to destroy malignant tumor cells. It allows the delivery of a precise dose of ionizing radiation to the tumor and its extensions, taking into account constraints such as the preservation of healthy tissues and the limitation of complications as much as possible.
Radiotherapy treatment results in destruction of tumor tissue and part of the healthy tissue; this is important to know in order to understand the occurrence of post-radiotherapy oral after-effects.
In head and neck tumors, the total radiation dose is between 60 and 70 Gy.
We distinguish:
- External (transcutaneous) radiotherapy : source of irradiation outside the patient:
Intensity-modulated conformal radiotherapy is currently the most widely used. The principle is to deliver optimal doses to a target tumor volume while preserving organs at risk (optic nerves, brainstem, parotid gland).
- brachytherapy: radioactive sources inside the body
- interstitial: sources placed in the tumor
- endocavitary: sources placed in a natural cavity in which the tumor develops
- Complications and after-effects of cervicofacial radiotherapy:
1-Radio mucositis: is an iatrogenic painful stomatitis, induced by ionizing radiation, characterized by functional signs of variable intensity (pain,
dysphagia, speech disorder). It persists 2-3 weeks after the end of radiotherapy
2-Ageusia:
– It is the disturbance of the taste function. It sets in from the 2nd or 3rd week of treatment.
3-Hyposialia:
- This is the consequence of irradiation of the main salivary glands
- The mucous membrane becomes dry, the lips are dry, cracked
- The patient has difficulty chewing, swallowing, wearing prostheses and speaking.
- Hyposialia persists for several months, it can be permanent and we then speak of xerostomia
- Oral candidiasis:
Radiotherapy-induced reduction in salivary flow has been suggested as an important factor in the predisposition of Candida albicans to colonize the oral environment
- Edema and trismus
- Edema particularly affects the submental and submandibular regions, the lower lip and the tongue.
- Sometimes requires occlusal adjustment to prevent biting.
- Progressive fibrosis and sclerosis of the TMJ and masticatory muscles.
- Erythema:
- Mainly affects the skin of the face and neck.
- Occurs after a dose of 3 to 4 Gy.
- Appearance similar to sunburn.
- The higher the dose absorbed, the more hair loss, cessation of glandular activity, dry and flaky skin will occur.
7- Radiogenic caries: Do not result directly from radiation. But mainly from xerostomia.
Develop 4 to 6 months after radiotherapy.
8- Post-radiation osteitis or ORN:
- Definition :
This is an iatrogenic osteitis which appears at doses of ionizing radiation = or > 50 Gy. (Extractions in territory irradiated by a dose of 50 Gy or more or any other mucosal wound expose to the risk of chronic osteitis.)
It is mainly observed at the level of the mandible.
It is the most serious and formidable complication, characterized by an increased risk of infections of the bone damaged by radiotherapy, particularly in the almost complete absence of repair mechanisms (reduction of irrigation).
The infection penetrates the previously injured bone and can spread without the defense mechanisms opposing it.
- Etiology
The main etiological determining factor is high-dose radiotherapy according to Sullivan. The incidence of ORN increases considerably when the total dose exceeds 60 Gys.
- Mucosal necrosis
- Dental extractions
- Periodontal surgery
- Prosthetic trauma.
The clinical picture is dominated by pain, bone denudation, fistulas and sometimes fracture
- Radiological signs of ORN:
The radiograph shows images of common osteitis (bone rarefaction, osteolysis); on the other hand, the images of sequestrum are very pathognomonic: the sequestrum appears as an area of bone that is certainly lysed but not totally defined in relation to the rest of the mandible.
- ACTION TO BE TAKEN
- Before radiotherapy:
-Careful clinical examination with diagnosis of the various lesions existing in the oral cavity.
- Establish a comprehensive patient care plan.
- Inform the patient about the possible risks,
- Hygienic and dietary instruction: oral hygiene.
- Eliminate all sources of infection,
- Be more radical when dealing with unmotivated patients.
- Be more conservative with the motivated patient.
- Perform dental and periodontal care.
- Insist on smoking cessation
- Reduce the time spent wearing prostheses
- Group the dental extractions, followed by ridge regularization with sutures.
- Depending on the oral and general condition, antibiotic therapy may be indicated; an average healing time of 20 days must be respected, without delaying the start of the X-ray.
-Fluoroprophylaxis
- During radiotherapy:
For the patient, this is the most difficult period of treatment.
These are mucositis, an aggression of radiotherapy, accompanied by functional signs
Our role is to:
- Relieve the patient
- Intercept or control bacterial or candidal infection
- Maintain good BD condition
- Manage emergencies that may arise during irradiation.
- Local care: frequent BDB 5-6 x/day based on sodium bicarbonate (14%)
- For pain: the choice falls on level II analgesics, short-term corticosteroids (1 mg/kg/day)
- Against candidal infection: antifungal (Fluconazole)
- Against bacterial infection: antibiotic therapy is the rule
- fitting of fluoride gutters 5 minutes per day, every day for life In case of necessary extraction: vital prognosis at risk
- Agreement of the attending physician
- Outside the irradiation field: least traumatic extraction under antibiotics, anesthesia without vasoconstrictor.
- In the irradiation field: interruption of treatment for 10 days then exo under ATB, anesthesia without vasoconstrictor then wait 10 days for the resumption of radiotherapy (patient hospitalization necessary).
- Accompany the procedure with constant and abundant irrigation with an antiseptic solution and make airtight sutures.
3-After radiotherapy:
A dental consultation will be carried out to assess the general condition and the condition of the oral cavity.
- Check the HBD
- Check fluoroprophylaxis
- Check for cavities and fillings
- Prescribing sialagogues
- Use of saliva substitutes
- Artificial saliva
- Salivary prosthesis
- Others: oil, butter, chewing gum
- Massages improve the plasticity of muscle and skin tissues
- The exercises should involve the mandible (with propulsion movement, diduction with mimic exercises)
- Located in the irradiation field:
- Obtain the radiotherapist’s agreement
- ATB coverage 2 days before => healing
- Anesthesia without vasoconstrictor, sutures
- Ideal time frame to respect: approximately 6 months (you must wait 6 months after the end of radiotherapy)
Outside the irradiation field: the patient is considered healthy
– – Strengthening bone healing through hyperbaric oxygen therapy
Adapted prosthetic rehabilitation after radiotherapy:
Problematic :
Fragility of the irradiated mucosa: risk of irritation, mucosal breach
Instability of prostheses (post-surgical anatomical context associated with hyposialia)
Means:
-Atraumatic prostheses (soft relining, regular check-ups)
-Use of implant anchors
-implantology in irradiated territory:
– Fuzzy scientific data
-Evaluation of the Benefit/Risk ratio:
Benefit:
- Improvement of orofacial functions (better retention of prostheses),
- Aesthetic improvement
Risk: Osteoradionecrosis (ORN)
Treatment of osteoradionecrosis:
– Medical treatment:
-Antibiotic therapy is not systematic due to the absence of deep infection in ORN sites; it is systematic during an invasive procedure.
-Anti-inflammatory during an inflammatory flare-up
-BDB antiseptic, analgesic
-Oxygen therapy
- Surgical treatment:
- sequestrectomy
- interruptive resection
PATIENTS ON BIPHOSPHONATES
DEFINITION :
Bisphosphonates are synthetic molecules, structurally similar to inorganic pyrophosphates. They exhibit high affinity for bone tissue and resistance to enzymatic hydrolysis.
Bisphosphonates are classified by generation:
- Non-amino bisphosphonates, 1st generation, also called simple bisphosphonates.
- 2nd and 3rd generation amino bisphosphonates called aminobisphosphonates
Modes of action of bisphosphonates:
The main effect of bisphosphonates is to inhibit bone resorption: they selectively bind to the crystalline structure of hydroxyapatite in the mineral matrix of bone tissue, then are phagocytosed by osteoclasts and cause their apoptosis .
Bisphosphonates also prevent soft tissue calcification through their action on cholesterol, elastin, and collagen in arterial walls.
They also inhibit angiogenesis and can induce avascular bone necrosis. This action would be responsible for hypovascularization of the jaws.
INDICATIONS:
Malignant pathologies
- multiple myeloma
- malignant hypercalcemia
- bone metastases and associated complications (pathological fractures, spinal cord compression, pain, etc.)
In these indications, bisphosphonates are administered intravenously (IV), at high doses and for prolonged periods.
Benign pathologies
- osteoporosis and fracture prevention
- Paget’s disease
- fibrous dysplasia of the bones
- osteogenesis imperfecta
- aseptic necrosis of the hip
Side effects of bisphosphonates:
Most side effects are minor and transient:
- Flu-like syndrome
- Digestive symptoms (nausea, vomiting, diarrhea, mouth ulcers, etc.)
- A disturbance in the blood count (anemia, leukopenia, thrombocytopenia),
- Neurological disorders (headaches, dizziness, hyperesthesia),
- An alteration of the immune response
- Ocular manifestations (uveitis, conjunctivitis),
- Arthralgia, myalgia.
- Osteonecrosis of the jaw (ONJ) is an adverse event first described in 2003.
Osteonecrosis of the jaws due to bisphosphonates:
In 2022 , the American Association of Oral and Maxillofacial Surgeons ( AAOMS ) defined this condition by the presence of three criteria :
- persistent bone denudation for more than eight weeks .
- No history of treatment with cervicofacial radiotherapy or recurrence
local tumor or metastases .
- previous or ongoing treatment with a bone resorption inhibitor (BRI) or an antiangiogenic agent.
Classification of ONMs according to AAOMS:
| Stadium | Signs |
| Patient at risk | Patient on antiresorbent |
| 0 | Absence of bone exposure Non-specific clinical or radiographic signs |
| 1 | Asymptomatic bone necrosis Absence of infection |
| 2 | Symptomatic bone necrosis Signs of infection |
| 3 | regional extension +/- fracture, fistula. |
-Radiological signs are absent at the beginning but after several months
a poorly defined osteolytic image appears, sometimes with the appearance of a bone sequestrum.
Action to take
- Before treatment with BPs:
AFSSAPS recommends:
- To carry out a clinical and radiological oral-dental assessment.
- to perform the necessary dental care and eliminate all proven or potential oral infections before starting treatment. Infected, non-restorable teeth and those with a poor prognosis must be extracted.
- Removable dentures must be atraumatic.
If the patient’s clinical condition allows it, it is preferable to only start treatment with bisphosphonates once the dental situation has cleared up and, if possible, after complete bone healing (ideally 120 days, but the time taken to implement treatments rarely allows this).
The patient should be informed about the risks of ONJ complications that may occur during and after treatment with BPs and the need for regular oral monitoring and to report any tooth mobility, pain, swelling, inflammation or ulceration of the mucosa. The importance of rigorous oral hygiene should also be made clear.
- During and after treatment:
The AFSSAPS strongly recommends:
- to carry out an oral and dental check-up every 4 months and at the slightest symptom. This follow-up must be done in collaboration with the oncologist.
- to detect and treat infectious foci using procedures that are as non-invasive as possible for the bone, periodontium and mucosa. Surgical procedures should be avoided as much as possible in favor of conservative therapies.
Examples of conservative attitudes according to the recommendations of AFSSAPS:
- For teeth with stage 1 to 2 mobility, it is preferable to use a periodontal splint to stabilize them rather than extract them.
- For teeth with a decaying carious lesion, but without pathological mobility, avulsion should be avoided by performing endodontic treatment, cutting the crown of the tooth flush with the gum and then reconstructing it with conventional techniques without altering the adjacent tissues.
Precautions to take during invasive procedures
Precautions regarding anesthesia
Intraosseous, intraseptal, and intraligamentous anesthesia should be avoided. AFSSAPS recommendations contraindicate the use of vasoconstrictors in patients receiving IV BPs.
Precautions for periodontal care Periodontal surgery is contraindicated. Precautions for dental extractions
Avulsions should be limited to non-saveable teeth, i.e. teeth with stage 3 mobility or in the presence of an active infectious focus.
Operating protocol :
- inform the patient of the risk associated with the surgical procedure, and obtain their consent;
- contact the prescribing physician to discuss the benefit/risk ratio of surgery ( the decision whether or not to temporarily stop BPs is taken in consultation with the prescribing physician );
- prescribe antiseptic mouthwashes (chlorhexidine) before and during the days following the procedure;
- prescribe antibiotic therapy to start the day before the procedure and continue until complete healing;
- perform a surgical procedure that is as minimally traumatic as possible;
- smooth out sharp bone edges;
- suture the edges without tension and hermetically
– implant surgery is contraindicated
-ONM prevention : It involves:
Information for health professionals (dentists, ENT specialists, maxillofacial surgeons, radiologists, oncologists, rheumatologists, general practitioners, geriatricians).
Regular monitoring of the oral health of people treated with bisphosphonates.
Establish a protocol for the care of hospitalized patients treated or not with bisphosphonates.
Management of a patient with osteonecrosis:
- Management varies depending on the severity of the condition in a hospital department of maxillofacial surgery, ENT or dentistry.
- Radiological assessment to assess the severity of the necrosis and the possible presence of sequestrum.
- Strict oral hygiene.
- Local analgesic and antiseptic treatment (chlorhexidine 0.1% mouthwash)
- Antibiotic therapy: Amoxicillin + metronidazole (1.5 g per day + 750 mg/day for 14 days)
- There is no consensus on the treatment of disabling ONJ. The goal of treatment is to control diffuse infections, cutaneous fistulas, reduce fractures, and return the patient to a non-disabling stage.
- It is possible to combine physical treatments, especially LASER (an improvement of microcirculation by vasodilation.
To remember
No therapeutic strategy has been the subject of consensus, given the multitude of parameters involved in maxillary osteonecrosis.
Prevention remains the most effective way to combat the onset of ONJ.
PATIENT UNDER TARGETED THERAPY
DEFINITION
Targeted cancer therapies are drugs that aim to block the growth and/or spread of tumor cells by specifically targeting certain abnormalities in them. Their main mode of action is through inhibition of the very mechanisms of oncogenesis, with significant specificity for cancer cells or their microenvironment. These can be intracellular inhibitors (small chemical molecules, including protein kinase inhibitors) or extracellular inhibitors (biological drugs, including monoclonal antibodies).
Denosumab:
It is a monoclonal antibody (IgG2) directed against the RANK ligand (anti-RANK-L) at the
surface of osteoclasts ( diagram 4 ), thus blocking the extracellular bone remodeling pathway, unlike BPs.
Its route of administration is exclusively subcutaneous and it would be eliminated more quickly from the jaw bones (6 months).
The risk of ONJ is significant with monthly denosumab injection in oncological indications and significantly lower in benign indications with twice-yearly injection.
MANAGEMENT OF INFECTIOUS RISK
Some targeted therapies can induce more or less severe immunosuppression, and therefore an increased susceptibility of the patient to infections. Before any dental treatment, it is important to perform a blood test with the measurement of leukocytes; and especially neutrophils. The risk of infection and its management should be determined by consultation between the dentist and the attending physician.
MANAGEMENT OF THE RISK OF OSTEONECROSIS OF THE JAW:
Denosumab leads to bone remodeling dysfunction that can induce ONJ in cases of trauma or infection. In the study by Fizazi et al., the incidence of ONJ appears similar to that occurring with BP (2% risk at two years for denosumab versus 1% for zoledronate). The clinical characteristics of these cases were comparable between treatment groups. Complete healing with conservative or surgical treatment was observed in 18% of patients treated with denosumab and 8% with zoledronic acid. The same management strategies appear to be applicable for denosumab and BP by analogy.
Surgical dental care
A therapeutic window can be established and decided with the treating physician after evaluating the patient’s benefit/risk ratio.
- Oral sanitation prior to surgery, through scaling and the prescription of chlorhexidine-based mouthwashes, is recommended to suppress inflammation and control bacterial contamination.
- Prophylactic antibiotic therapy is necessary and should begin the day before the procedure, until the mucosa has healed.
- The strict hygiene and asepsis conditions of the dental office and the care team must be respected.
Local anesthesia should be without vasoconstrictors and intraligamentous, intraseptal and intraosseous anesthesia are not recommended.
PATIENT CARE AFTER TARGETED THERAPY:
Denosumab has a short half-life (28 days). A return to physiological state of osteoclasts and osteoblasts is observed approximately 6 months after the last injection. Therefore, until this time, it is recommended to apply precautions regarding the risk of ONJ.
The time to return to normal of hematological values after stopping targeted therapies is not known, but will be faster after stopping tyrosine kinase inhibitors, since they have a short half-life (from a few hours to a few days), than after stopping monoclonal antibodies which have a longer half-life (from several days to several weeks).
It is recommended in the weeks and months following the discontinuation of targeted therapy to carry out a blood test before any invasive procedure in order to check the hematological values.
CONCLUSION
The role of the dentist in the care of these patients is essential to prevent and reduce the risk of ONJ. An oral health assessment before treatment begins allows for planning the restoration of the oral cavity and thus the safe initiation of treatment. Once treatment has been initiated, all conservative dental care can be performed without the risk of ONJ, while taking special anti-infectious precautions for invasive procedures with a significant risk of ONJ.
Irradiated patients Patients under biphosphonates Patients under targeted therapy
Deep cavities may require root canal treatment to save the tooth.
Dental veneers can correct stained or malformed teeth.
Misaligned teeth can cause speech problems.
Dental implants prevent bone loss in the jaw.
Antiseptic mouthwashes reduce bacteria that cause infections.
Decayed baby teeth must be treated to avoid complications.
An electric toothbrush cleans more effectively than a manual one.