management of cancer patients

Management of Patients Undergoing Cancer Therapy

Hanan Shanab

• Few information obtained from cancer pt. which is relevant to the surgeon. .. Like:

– The type of treatment.– The duration of treatment .– Whether he is an outpatient or inpatient

(1) surgery; (2) radiation therapy.(3) Chemotherapy.

There are three treatment modalities involved in eradicating head and neck cancer:

Combination Chemoradiotherapy

• Cetuximab is a chimeric monoclonal antibody that targets epidermal growth factor receptor. The FDA approved cetuximab for treatment of squamous cell carcinoma of the head and neck in March 2006.

Treatment modalities involved in eradicating head and neck cancer:

(1) surgery; (2) radiation therapy.(3) Chemotherapy.

(1) Immunotherapy(2) Gene therapy.(3) Antiangiogenic therapy.

Pt . Evaluation before cancer therapy:

– Age of the pt.– Condition of dentition.– Level of oral hygiene and pt. attitude.– Radiation field and dose.

Guidelines for extraction before RTx

• All questionable ,carious teeth in the field of radiation (>6000 cG) must be extracted.

• Optimal time for extraction is 21 days before the beginning of RTx (not less than 2 w).

• Less optimally, extraction can be done within 4 months after completion of RTx.(after HBO)

• Perform radical alveolectomy with primary soft tissue closure following extraction.

Radiotherapy

• More effective on well oxygenated and mitotically active..– Induce cell necrosis .– Microvascular damage.– Parenchyma and stromal damage.

Types of Radiation therapy

1-External beam radiation.– (tumoricidal dose is 6000-7600 cGy)– Hyperfractionated to 200 cGy for 5 days/week.– 150-180 cGy twice daily-3-4 days/week

2- Interstitial Radiotherapy (brachytherapy).RadiumIridium- ½ life 74 days-no gaseous by product

3-Neutron Beam Radiotherapy.Rarely used today

Chemotherapy

TYPES:

• Alkylating agents • Antibiotics.

•Antimetabolites.•Hormons.•Mitotic inhibitors

CCS CCNS

Complication of Cancer Therapy

Complication of Cancer Therapy

• 1-Mucositis.• 2- Xerostomia.• 3-secondary infection.• 4- bleeding.• 5-Muscle Trismus.• 6-osteoradionecrosis.• 7-alopecia.

– More in non keratinized tissues like palatal , buccal mucosa , ventral tongue ..

– Started by the second week of radiation therapy.(if the dose 200 cGy/week)

– 7th -14th day after chemotherapy.

Complications of Cancer Therapy

1-Mucositis.

• More higher in young pt…high division rate.

• Produce red,raw, tender oral mucosa with sloughing epi. ..Like burn..

• Pt. has dysphagia, pain, loss of taste difficulty in eating which increase systemic infection.

Complication..Mucositis.

Its generally subsides 1-2 weeks after completion of treatment.

WHO Scale for Oral Mucositis

• Degree 0:is when there are no signs or symptoms. • Degree 1 :is when the mucosa is erythematose and painful. • Degree 2 :is characterized by ulcers, and the patient can eat

normally.

• Degree 3 :is when the patient has ulcers and can only

drink fluids. • Degree 4 :is when the patient cannot eat or drink.

Phases of Mucositis

Phase 1 (Initiation): radiation or chemotherapy causes DNA damage in basal epithelial cells and generates reactive oxygen species (ROS), which further damage cells and blood vessels in the submucosa.

Phase 2 (Signaling): chemotherapy, radiation, induce apoptosis and upregulated inflammatory cytokines in cells.

Phase 3 (Amplification): inflammatory cytokines produce further tissue damage, amplifying signaling cascades and the injury process.

Phase 4 (Ulceration): loss of mucosal integrity produces extremely painful lesions, providing portals of entry for bacteria, viruses, and fungi.

• Phase 5 (Healing): proliferation, differentiation, and migration of epithelial cells to restore the integrity of the mucosa.

Management of Mucositis

• 1-A bland mouth rinse (salt and water).. To keep ulcerated areas clean as possible.

• 2-Topical anesthesia and /or antihistamine solution or with coating agents (milk of magnesia).

• 3-Anti microbial-Chlorohixidine.12%

• 4-Anti-inflammatory or topical steroids.

• 5-Diet consisting of soft food, proteins, and vitamins supplements at therapeutic level.

Management of Mucositis

• 6-Oral lubricants and lip palm ..containing (beeswax).

• 7-Avoidance of alcohol, tobacco and irritant foods

2-Xerostomia

• If major salivary gland have been irradiated.

• Occur following the onset of mucositis.– Altered taste sensation.– Increase susceptibility for caries and mucosal

inflammation.– Difficult in swallowing, speech.

• Side effects of pain medicine: Opioids for painful swallowing may cause dry mouth and constipation.

• Recommended sugarless lemon drops.

• Sorbitol-based chewing gum.

• Buffered solution of glycerine and water or salivary substitutes.

Management of Xerstomia

3-Secondary infection:

Causes:• Decrease in quantity of salivary flow.• Immunosuppressed (WBC<2000/mm3).• In pt. receiving chemotherapy and antibiotics.

Fungal infection

• Candida albicans• Candidal infection produce pain, burning taste and

intolerance to certain foods.• The most common type is pseudomembranous

candidiasis.. Curdled milk

• Other forms (angular cheilosis and less common hypertrophic form.

Bacterial infection

• Shift occurs in the oral flora to gram –ve that’s Normally inhabit the GIT or respiratory tract like Pseudomonas, Klebsielaa, Proteus, E coli, Enterobacter.

Viral infection

• Recurrent herpes simplex (HSV).• Occur often during chemotherapy and less

frequent with radiotherapy.• Takes longer to heal.• Mimic aphthous ulcer on nonkeratinized mucosa.

Management of Infection

• Cytology study.• Culture any non

healed ulcerations for Dx and for accurate treatment.

For Candida infection :

– Oral nystatin suspention 100,000 IU/ml 4-5 times daily.

– Cotrimazole (10mg 5 times daily).– Systemic ketoconazol(Nizoral).– Alternatively, putting pt. on granulocyte (monocyte)

colony-stimulating factor to elevate neutrophil count to normal.

Management of Infection

For Viral infection:

• Enzyme-linked immunoassay for accurate Dx.

• For HSV antibody-positive pt:– Acyclovir, famcyclovir, valcyclovir.– Daily dose of at least 1 g.

Management of Infection

4- Bleeding

• Pt. undergo total body irradiation• High dose chemotherapy.

Thrombocytopenia

• Clinical signs:– Plat. <50,000 cells/mm3– Petechia, purpra on lateral margin of tongue.– Gingival bleeding.– Submucosal hemorrhage… from minor trauma

Management of Bleeding

• Avoid trauma to the oral cavity.• Control bleeding by local measures by

– Pressure.– Gelatine sponge.– Thrombin or microfibrillar collagen.– Antifibrinolytic rinse .. Amicar syrup 250mg/ml. on

soft vinyl mouth guard.• Platelet transfusion in sever cases.

5-Neural and chemosensory changes

• Diminshed taste sensation… damage of microvilli of taste cells.

• Pt on chemotherapy complaints of – bitter taste, – unpleasent odors – conditioned aversion of foods

• Neurotoxicity effect from chemotherapy (vincristine and vinblastin).

• Occur in peripheral nerves.• Pt. experience pain in molar area bilateral.

Management

• 1-Restore taste sensation within 3-4 months after completion of radiotherapy.

• 2-In chronic loss of taste, zinc supplementation.

Silverman recommends 220 mg of zinc 2x/day.

• 3-No effective treatment for completely restores damaged taste.

6-Muscle Trismus

• Caused by radiation therapy.

• Damage to the vasculature of ms.(obliterative endoartritis).

– Progressive later dysphagia from fibrosis in the pharyngeal musculature

– reduces nutritional intake

– promotes aspiration.

Muscle Trismus

• Pneumonia and respiratory failure: Patients who have trouble swallowing may aspirate when trying to eat or drink.

• Poor nutrition: Being unable to swallow normally makes it hard to eat well. Wounds heal more slowly and the body is less able to fight off infections.

• Use of tubefeeding: A patient who is not able to take in enough food by mouth may be fed through a tube.

management

• Mouth block should be placed during radiotherapy.

• Perform daily stretching exercises to improve trismus. By using tongue plates for 3 times aday for 10 min

• Apply warm, moist heat on the area.

Muscle Trismus

7-Osteoradionecrosis

• Exposed bone for 6 months after high dose of radiation.

• Results from:– Radiation.– Three-H tissue.(hypocellularity,hypoxia, hypovascularity)

– Tissue breakdown..necrosis

– nonhealing wound.

• The mandible more affected than maxilla

When the radiation dose is >7500 cGy.

• Clinically..– Exposed bone, loss of soft tissue and bone.– Pain (dysesthesia/anasthesia).– Pathological fracture and orocutaneous fistula.– Trismus.– Soft tissue necrosis.

• Radiographic..– Diffuse radiolucency without sclerotic demarcation.– Mottled osteoporosis and sclerotic areas after bone sequestra are

formed.

Management of ORN

Conservative management

• Daily local irrigation..salineor chlorohixidine.2%

• Systemic antibiotics.

• Avoidance of irritants..tobaco,alcohol,denture.

• Good oral hyigene instructions.

• General removal of sequestrum in sequestrating lesions.

– It is esablished protocols of the Undersea and Hyperbaric Medicine Society.

– Either monoplace or multiplace chamber.– Each session 100% O2 @ 2.4 ATA for 90 min.– Increase the vascularity by 75%

HBO protocol

• Allow healing …. – Angiogenesis.– Inducing fibroplasia and neocellularity.– Promoting survival of osteoprogenitor cells.– Promoting the formation of functional periosteum.

HBO Protocol

Indication of HBO

1. Prophylaxis.. In surgical procedure in irradiated field.

2. Treatment of ORN.3. Before bony and soft tissue reconstruction and

before placement of dental implants in irradiated bone.

4. Treatment of Necrotizing Fascitis, gas gangrene and chronic refractory osteomyelitis.

HBO Protocol

Prophylactic HBO before oral surgical procedure

Marx et al 1991 300 pts Incidence of ORN in non –HBO 30% compared with 5.4% in –

HBO group. HBO is very cost effective

Against:× overall risk of developing ORN with preradiation or postradiation

extractions is quite low.× HBO therapy is expensive.× it is time consuming.

× HBO has not definitely been shown to prevent the development of ORN, and it does not reverse established ORN.

Prophylactic HBO before oral surgical procedure

• 20 sessions before• 100% O2 @2.4ATA-90 min.• Once daily treatment 5 days/week.

• 10 sessions post op.

20/10

Prophylactic HBO before dental implants

Animal and clinical studies treated with HBO showed: • Improved soft tissue wound healing . • Decreased dehiscence after implants with HBO.This study also showed:• Improved torque removal forces of implants.• Greater quantity of bone-implant contact in irradiated rabbit tibias

treated with HBO compared with that not treated.

Against:The potential benefit of HBO therapy balanced against its cost and potential complications doesn’t justify its use.

In 1997, the Journal of Oral and Maxillofacial Surgery highlighted a similar controversy. Keller and Larsen took opposing views. Keller examined 14 studies of implants in radiated tissue without HBO, which had remarkable success.

Evidence supports enhanced long-term survival in all sites, but the clinician must weigh the availability, complications, and added cost in the decision-making process.

Protocol for HBO therapy before implant placement

• Good oral hygiene before &after implantation.

• The use of the longest &widesttype and maximum no. of implants.

• Implant delay until 6 months after radiation.

• Cessation of smoking.• Preop. HBO ( increase integration time by 3

months).• This protocol is the same for maxilla and the

mandible.

Protocol for HBO therapy before implant placement

• Previously integrated implants should be buried before irradiation and subjected to 20 HBO ttt before uncovering.

Protocol for HBO therapy before implant placement

Gidlines of using HBO

Osteoradionecrosis Treatment

Exposed Bone

Stage I30 Session HBO

Stage I ResponderLocal debridment10 Session HBO

1-Bone softens.2-Granulation tissue develops

Bone and mucosa healed

Stage INonresponder

Stage IISurgical debridement

10 Session HBO

Resolution of ORN Resolution of ORN

Exposed Bone with:A- not respond to stageII.B-pt who presents with:1-pathologic Fx or2-orocutaneous Fistula or3-osteolysis to inferior border of the mandible (radiographic).

Stage III30 Session HBO

1-continuity resection.2-Jaw stabilization.3-Soft tissue flap if needed.

10 Session HBO

Resolution of ORN

Continued exposure

Dehiscence, cont. bone exposure

• However, several studies have shown some benefit in using HBO in the management of Stage I and II ORN.

• Most reconstructive surgeons currently use vascularized free tissue transfers instead of HBO therapy in the management of stage III ORN.

Early criticism of microvascular reconstruction of the mandible included:

• inadequate bone stock for prosthetic dental reconstruction,

• prolonged ICU stay and hospitalization, • increased donor site morbidity.

Experience with microvascular reconstruction has lessened these concerns.

Complication of HBO

1-Barotrauma:Middle ear. Nasal sinus.Inner ear .Lung.Teeth.

2-oxygen toxicity:CNS..seizur .Lung.. Pneumothorax &air embolism.

Complication of HBO

3- confinement anxiety.

4- Ocular defect..myopia and catarct growth

Complication of HBO

Contraindication of HBO

Guidelines for tooth extraction in Radio. or chemotherapy pt.

• Perform extraction with minimal trauma.• Within first 4 months of radiotherapy

‘’Golden Window’’.

• Trim bone at wound margins to eliminate sharp edges.

• Obtain primary closure.• Avoid intraalveolar haemostatic packing

agents that can serve as nidus of microbial growth.

Guidelines for tooth extraction in Radio. or chemotherapy pt.

• Transfuse if the platelet count is less than 50,000/mm3.

• Delay if WBC < 2000/mm3. or absolute neutrophil is <1000/mm3. or expected to be this level within 10 days.

• Prophylactic antibiotics (cephalosporin) may be used with extractions are mandatory.

Guidelines for tooth extraction in Radio. or chemotherapy pt.

• Prophylaxis:– Penicillin V 500mg q4h one day pre op.– Continue for at least 3 days post op.

Bisphosphonate

• It is a synthetic analog of inorganic pyrophosphate.• Which has high affinity to calcium.• Accumulate over extended periods in mineralized bone

matrix.

• Used in : – Paget’s disease. – Osteoporosis. – hypercalcemia of malignancy.– Multiple myeloma in bone.– metastatic solid cancer like breast.

• Action :– Arrest bone loss.– Increase bone density. – Decrease bone fracture.

Rout of Administration

•Etidronate (Didronell)•Pamidronate (Aredia)•Zoledronic acid (Zometal)

What does it do?

• Bisphosphonate alter bone remodeling.• The drug is taken up by osteoclasts (cytoplasm).

• Inhibit its function.• Induce apoptotic cell death.

• Inhibits osteoblast mediated osteoclast resorbtion.• Antiangeogenic properties.

• In oral cavity, the maxilla and mandible are subjected to constant stress from masticatory forces.

• The bone becomes brittle and unable to repair physiological micro-fractures occur in human skeleton.

• So BRONJ..as a result from:– Low bone metabolism.– Local trauma– Increase demand for bone repair.– Infection– Hypovascularity.

Table 3. Dental risk factors for osteonecrosis of the jaw (ONJ).° Clinically and radiographically evident periodontitis17,38: severe periodontitis with chronic infection andinflammation of the supporting alveolar bone is a major risk factor for ONJ. This condition may be present in3%–5% of seventh-decade and older adults who still have teeth17° Tooth extraction: up to 60% of cases of ONJ have been reported in patients having had a recent tooth extraction1,2,17,35,38,50,66° Concomitant or past oral infection35,48,66,77,78° Failing root canal treatment with retained periapical infection35° Trauma caused by removable dentures2,35,38,77° Implant placement, past or current1,2,17,78: newly placed implants have a poor healing rate in patients receivingIV bisphosphonates and hence are contraindicated1. Previously placed implants may have a higher rate offailure. This warrants further study

Table 4. Systemic and other risk factors for osteonecrosis of the jaw (ONJ).° Concomitant malignant disease and chemotherapy1,17,38,66,79° Glucocorticoid therapy1,17,35,66,80° Diabetes1,38,81° Advanced age: in review of cases of ONJ in patients with multiple myeloma, there was a 9% increase in therisk of developing ONJ with each decade of life82° Smoking and alcohol need to be evaluated further

Clinical picture of BRONJ

In early stage:• No radiographic manifestation.• Bone exposure • Soft tissue dehiscence.• Secondary infection.• Parasthesia from peripheral nerve compression

Sever pain

BRONJ Staging and Treatment

• At RiskNo apparent exposed/necrotic bone in pt.

treated with oral or I.V bisphosphonate.• Treatment:

– No treatmen.t– Pt. education.

Stage 1:•Exposed /necrotic bone.•Asymptomatic.•No evidence of infection.

Treatment:•Antibacterial mouth rinse.•F/U every 3 months.•Review indication for continued bisphosphonate therapy.•Pt. education.

Stage2:•Exposed/necrotic bone.•Pain and erythema. In the area of exposed bone.•With/without purulent drainage.

•Treatment:•Symptomatic treatment.•Broad spectrum A/B.•Pain control.•Superficial debridement to relieve soft tissue irritation.

Stage3:•Exposed/necrotic bone.•Pain and infection•One or more of the following:•Extraoral fistula.•Osteolysis extending to the mandibular border.

•Treatment: •Broad spectrum A/B.•Pain control.•Superficial debridement/resection for palliation and pain.

Full understanding of the behavior of the cancer as well as the treatment modality available will help you in optimal management of those patient

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