Oral Cancer Flashcards
what therapies are utilized in oral cancer
- surgery
- radiation
- chemotherapy
what are the types of surgery used in oral cancer
- biopsy/radical neck dissection
- mandibular resection/graft
- maxillectomy/oro-antral communication
- glossectomy
where would radiation be targeted at in oral cancer
- base of tongue
- nasopharynx
what are the two ways radiation can be delivered in oral cancer and which is more common
- fixed beam radiation
- intensity modulated radiation therapy (IMRT): more common
what is fixed beam radiation therapy
all the tissue between the portals receive the same dose
- more like a PA xray
what is intensity modulated radiation therapy
- a constantly moving beam administers different amounts of radiation to the tissues
- the tumor receives the highest amount of radiation
- minimal amounts of radiation are applied to vital structures - spinal cord, salivary glands
- more like a pano
what is fractionation
the application of radiation therapy in smaller consecutive doses to minimize the lethal effects and limit the side effects of the therapy
what is the dose used in fractionation
5 times a week for 5 to 7 consecutive weeks
what are the 5 Rs of fractionation
- repair
- redistribution
- repopulation
- reoxygenation
- radiosensitivity
radiation causes _____ damage to normal and malignant cells
sub-lethal
the repair pathways are often blocked or impaired by:
the malignant cells resulting in death
describe redistribution
- DNA is more sensitive during G2 and M phases
- most stable is S phase
- fractionation provides multiple opportunities to affect the cells when they are in the sensitive phase
describe repopulation
- rapid repopulation of the malignant cells can occur approximately 4-5 weeks after the initial radiation dose
- fractionation over 5-7 weeks prevents the rapid repopulation of these cells
describe reoxygenation
- tumor cells are more resistance to radiation in hypoxic environments
- fractionaction increases the odds that the tumor cells will be in a nutrient field during radiation
- the outermost tumor cells are destroyed exposing the hypoxic inner layers of tumor cells
describe radiosensitivity
- involves the recognition of certain proteins, receptors and kinases that may make cells less sensitive to radiation
- recognizing the presence of the components may help predict the success of radiation therapy in certain cases
what should be done prior to radiation
- complete dental/perio evaluation
- establish a baseline
- previous dental experience/frequency
- extract suspect teeth in the radiation field
- complete prophy and restorative tx
- fabricate custom fluoride trays
what are the indications for extractions prior to radiation therapy
- non restorable caries or high caries rate
- periodontal pocketing greater than 5mm
- furcation involvement
- impacted teeth
what are the complications of radiation
- xerostomia/dental caries
- mucositis
- osteoradionecrosis
- trismus
- hypoguesia/dysgeusia
- nutritional deficiency
what salivary glands are most affected by radiation
serous glands such as parotid and submandibular
what types of glands are each of the major salivary glands
- parotid: seroud
- submandibular: serous/mucous
- sublingual: primarily mucous
salivary hypofunction can occur when exposed to radiation doses as low as:
25 Gy
the rapid formation and progression of dental caries is mainly attributed to the:
reduced quality and quantity of the saliva
what are the treatments for xerostomia
- water
- salivary substitutes
- minimize carbohydrate and alcohol intake
- alcohol free mouth rinses: peridex and crest pro health
- listerine
- sugar free gum
what is xylitol from and why is it effective
- sugar alcohol originally derived from birch trees
- commercially produced from corn cobs
- caries causing bacteria are unable to metabolize it
what is the therapeutic amount of xylitol
- ingesting 6-8g daily can decrease aries
- frequency of use more important that quantity
how is xylitol packaged
as sweetener in gums, mints, candies or oral rinses
how much xylitol per piece of ice breaker cubes, epic gum, epic mints, spry gum, and xylimelts
- ice breakers ice cubes: 1g/piece
- epic gum: 1g/piece
- epic mints: 0.5/piece
- spry gum: 0.72/piece
-xylimelts: 0.5/piece
what are the issues with xylitol
- can cause gastric issues with some patients: primarily when over 50g ingested daily
- extremely toxic to dogs
what are the sialogogues and the dosage
- cholinergic agonist
- pilocarpine hydrochloride: 5-10mg tid. max dose 30mg/day. may take 12 weeks to see results
how is fluoride therapy used
- rinse, brush, floss, fluoride trays
- 10 minutes a day
- no food or drink for 30 minutes
- best results when used prior to bedtime
what are the types of fluoride
1.1% sodium fluoride
- 0.4% stannous fluoride
what is 0.4% stannous fluoride better for and what is its downside
- better for root caries
- may stain the teeth brown
what is mucositis
- oral mucosa exposed to radiation becomes edematous, erythematous and ulcerated
- the condition can be extremely painful and cause issues with mastication and swallowingw
when do the signs and symptoms of mucositis often arise
after the second week of therapy and may last a few weeks after the completion of treatment
what should you recommend to patients with mild pain with mucositis
- maintain OH
- bland oral rinses
- baking soda/water with or without salt
what should you recommend for topical oral pain management with mucositis
- caphosol
- magic mouthwash: viscous lidocaine, maaloc, diphenhydramine with or without nystatin
- mild analgesics
what is the magic mouthwash made of
- 1 part (120mL) diphenhydramine 12.5mg/5mL
- 1 part (120mL) maalox
- 1 part (120mL) viscous lidocaine 2%
- 1 part (120mL) nystatin susp. 100,000 U/mL (optional)
what is caphsol used for
mucositis to soothe the gums- its a rinse
what do you recommend for patients with moderate pain with mucositis
- addition of moderate strength opiods
- hydrocodone and oxycodone
- altered diet (soft)
what do you recommend for patients with severe pain with mucositis
- addition of strong opiods- oxycodone, morphine, oxymorphone
- may need nasogastric or PEG tube
what is osteoradionecrosis
radiation results in vascular changes in the bone limiting the blood supply and the ability to heal after trauma or extractions
ORN is associated with radiation doses above _____
50Gy
ORN is more common in the _____ because
mandible because of less vascularity
how can you prevent ORN
- extraction of questionable teeth prior to radiation therapy
- complete RCT if it is an option
- if a post radiation TE is necessary hyperbaric oxygen therapy may be necessary:20 dives prior to TE/10 dives after TE
how many times is HBO needed
once a lifetime
what is stage 0 of ONJ
- no exposed bone but pt is sympotmatic
- radiographic changes may be present
what is the tx for stage 0 ONJ
- periodic monitoring
- systemic management - antibiotics and pain meds
what is stage 1 of ONJ and the tx
- bone is exposed, asymptomatic, no infection present
- ts: monitor closely for 8 weeks, if no changes monitor quarterly. meticulous home care. antimicrobial oral rinses. remove loose sequestra if present
what is stage 2 ONJ and the tx
- exposed bone with associated pain
- purulent exudate may be present
- tx: same as stage 1. addition of systemic antibiotics (penicillin, clindamycin, doxycycline). superficial debridement to relieve soft tissue irritation. possible HBO therapy
what is stage 3 ONJ and the tx
- exposed bone with pain and one of the following:
- pathologic fracture
- extra oral fistula
- necrotic lesion extends to the inferior border
- tx: surgical debridement or resection. antibiotic therapy. possible HBO
when does trismus occur
when the pterygoid region is irradiated
when is trismus noticed
near the completion of radiation therapy
how does radiation cause trismus
may cause spasms or fibrosis of the TMJ and muscles of mastication resulting in a limited range of motion
how long does trismus post radiation therapy last
may last several months but not permanent usually
what is the treatment for trismus
- warm moist heat
- massage
- physical therapy: tongue depressors, therabite, dynasplint
permanent taste loss may occur with a cumulative dose of:
60 Gy
taste may return at ____ dosages
lesser than 60 Gy
what may also contribute to alterations in taste
xerostomia and mucositis
hypogeusia may or may not improve depending on:
the site and amount of radiation
what is the tx for hypogeusia/dygeusia
- water/salivary substitutes
- constantly monitor for bacterial or fungal infections
what is the protocol for oral radiation and removable appliances
- wait 6-9 months after the completion of radiation to fabricate dentures and RPDs
- educate the pt
- limit the amount of use
- place silicone liners (GC reline)
- set a 3 month recall
what is the definition of chemotherapy
a form of cancer treatment that involves taking one or more of a type of drug that interferes with the DNA genes of fast growing cells. these drugs are further subdivided into specific classes such as alkylating agents, antimetabolites, anthracyclines, and topoisomerase inhibitors
how is chemotherapy administered
- IV infusion: port a cath
- pill
what are the effects of chemotherapy
- immune system suppression
- mucositis
- xerostomia
- bleeding
- hypogeusia/dysgeusia
what dental tx should be done prior to tx
- complete dental examination
- prophylaxis/SRP
- extraction of teeth with non restorable caries, poor periodontal prognosis
- complete any needed endodontic therapy
what is the protocol for dental tx during chemo and when is the lowest blood count
- avoid any dental treatment if possible during chemotherapy
- pts usually reach their “nadir” (lowest blood counts) 7-14 days after a course of chemo
- if tx is needed, blood counts are usually best just prior to their next course of chemo
what is the protocol for oral surgery during chemo
- any invasive procedures get recent blood counts
- absolute neutrophil count greater than 1000/mm^3
- platelet count greater than 75,000/mm^3
when is antibiotic prophylaxis recommended in chemo patients
- presence of port-a-cath
- neutrophils between 1,000 and 2,000/mm^3
how can oral complications be prevented with chemo and immunosupression caused by it
- brush and light flossing
- chlorhexidine rinses (non-alcohol)
- neutral rinse (baking soda and water)
- treat opportunistic infections:
- fungal (candida) with nystatin or fluconazole
- viral (herpetic) with acyclovir or famciclovir
what is recommended for mild pain from mucositis from chemo
- maintain OH
- use bland oral rinses
- use topical oral pain management: caphosol, magic mouthwash
- mild analgesics
what is the recommended for moderate and severe pain with mucositis from chemo
same as with radiation
when does xerostomia usually resolve after chemo
within a few months after tx is completed
xerostomia can provide the ideal environment for:
opportunistic infections
what are the tx for xerostomia
- water
- salivary substitutes
- sugar free gum
- monitor carbohydrate intake
- sialogogues
what are the bleeding considerations with chemo
- chemo can decrease the platelet count
- avoid invasive dental procedures if possible
- gentle brushing and flossing
how long does hypogeusia/dysgeusia last with chemo
temporary
hypogeusia/dysgeusia effects from chemo may be related to:
- mucositis
- xerostomia
- bacteria or fungal infections
chemotherapy is used to destroy:
the bone marrow
what happens in a bone marrow transplant
hematopoietic stem cells are transplanted to repopulated the bone marrow
what are the 3 types of bone marrow transplants
- autologous
- allogeneic
- syngeneic
describe the autologous bone marrow transplant
the patients own bone marrow or stem cells are removed and preserved for transplantation
describe allogenic bone marrow transplant
- bone marrow or stem cells from a HLA matched individual are used for transplant
describe syngeneic bone marrow transplant
- bone marrow or stem cells from an identical twin are used for transplantation
what is the dental treatment protocol prior to BMT
treatment prior to transplant is similar tot hat of other chemo patients
what is the dental treatment protocol after BMT
- 0-100 days: OH, emergency, and supportive care only
- 100-365 days: OH, emergency and xerostomia management only
- 365+ days: routine dental care
graft versus host disease occurs primarily with what type of transplant
allogenic
what are the oral manifestations of graft versus host disease
- mucositis
- infections: bacterial, viral and fungal
- mucosal atrophy
- xerostomia
what are the antiresorptive medicatiosn
- bisphosphonates
- RANK ligand inhibitors
what are bisphosphonates used for and what do they do
-used for tx of osteoporosis, Paget’s disease and osteogenesis imperfecta
- now used for adjunctive treatment of cancer
- decrease osteoclastic activity
describe the non nitrogen bisphosphonates, what they are used for and what do they do
- oral only
- etidronate
- clodronate
- primarily used for tx of pagets disease
- low potency
- prevents osteoclast proliferation by inhibiting ATP dependent enzymes
describe the administration of nitrogen containing bisphosphonates and their MOA
- Oral or IV
- MOA: prevents binding of essential proteins to the cell membrane leading to apoptosis
- prevents adhesion of the osteoclasts tot he hydroxyapatite crystals by altering the cell cytoskeleton
oral nitrogen containing bisphosphonates are approved for the use in the tx of:
pagets disease and osteoporosis
what are the oral nitrogen containing bisphosphonates
- alendronate (fosamax)
- risendronate (actonel)
- ibandronate (boniva)
what IV nitrogen containing bisphosphonate is used in the tx of osteoporosis
Zolendronate (reclast) -5mg/year
what IV nitrogen containing bisphosphonate is used in the tx of bone metastases
- zolendronate - 4mg/3 weeks
- pamidronate- 90mg/3 weeks
what are the antiresorptive agents and their dose
- osteoporosis: prolia - 60mg/6 months
- bone metastases - Xgeva- 120mg/4 weeks
what is the MOA of antiresorptive agents
- tumor cells promotes the release of RANK ligand from the osteoblast within turn promote the production of osteoclasts
- denosumab binds to the RANK ligand and prevents osteoclast proliferation
what are the antiangiogenic medications
- tyrosine kinase inhibitor: Sutent and Nexavar
- humanized monoclonal antibody: Avastin
what is the MOA of antiangiogenic medications
recognizes and blocks vascular endothelial growth factor (VEGF) a protein needed for angiogenesis
antiangiogenic medications are used in the tx of:
GI tumors, renal cell carcinomas, and neuroendocrine tumors
what are the drug related risks of MRONJ
- potency
- oral non nitrogen containing bisphosphonates
- oral nitrogen containing bisphosphonates - 0.4-4%
- IV bisphosphonates (4-12%)
- aredia and zometa
- XGEVA
- IV bisphosphonates plus an antiangiogenic medication
- duration: increased risk after18 months
what are the local risk factors in surgery/trauma with MRONJ
- dental extractions
- osseous surgery: periodontal, apicoectomy
- implant placement
what are the local risk factors with anatomy and MRONJ
- mandible vs maxilla (2:1 ratio)
- tori, exostoses
- mylohyoid ridge
what are the demographic factors for MRONJ
- age: 9% increased risk with each passing decade
- race: caucasian
what are the systemic factors that increase MRONJ risk
- primary cancer dx:
- multiple myeloma- highest risk
- breast cancer- 2nd highest risk
- concurrent osteopenia or osteoporosis diagnosis
prior to starting therapy on antiresorptive medications:
- extract non restorable and questionable teeth along with alveoplasty, tori removal
- complete necessary periodontal therapy
- complete any endo and restorative work
what is the protocol with removable appliances with patients on antiresorptive medications
- limit amount of sue
- place silicone liners if necessary
- educate the pt
- 3 month recall intervals
while on antiresorptive/antiangiogenic agent therapy, if any surgery or invasive procedures are necessary:
a 3 month drug holiday should be complete prior to therapy and use of antiresorptive/antiangiogenic agents should not be started again until after osseous healing has occurred
_____ of the bisphosphonate is excreted by the kidneys within hours of ingestion or infusion
50%
remaining 50% of bisphosphonates after excretion are deposited in the:
skeleton
describe osteocytes with bisphosphonates and the resting bones
- make up 85% of resting bone
- have a long lifespan
- have a low affinity for bisphosphonates
- bisphosphonates loosely bind to the surface and are removed within days
describe osteoclasts with bisphosphonates and the resting bones
- make up 2-4% of resting bone
- have a life span of 2 weeks
- 8x the affinity for bisphosphonates
- upon death of osteoclasts, bisphosphonates are reabsorbed by the skeleton or excreted by the kidneys
describe the osteoblasts with bisphosphonates and the resting bones
- make up 10-12% of resting bone
- have a lifespan of 2 months
- 4x affinity for bisphosphonates
- bisphosphonates are incorporated into the bone instead of being released
bisphosphonates are primarily distributed in areas of:
active bone remodeling
stem cell development into osteoclasts is ____
minimized
in remodeling areas what does an increase in bisphosphonates do
disrupts synergistic make up of the basic multicellular unit: osteoclasts, osteoblasts, osteocytes and local vascular supply
what is the alternative vacation based on the physiology with bisphosphonates
- 2 month presurgical holiday
- averagae 4 month postsurgical holiday - ideally 8 months
describe the 2 month presurgical holiday with bisphosphonates
- osteoclasts are the only reservoir for the bisphosphonates- allows for 4 life cycles
- minimal remaining bisphosphonate
why is the post surgical bisphosphonate drug holiday needed
- necessary time needed for bones to return to resting state
- no needed alteration in bisphosphonate therapy if planned correctly
what does denosumab do, its half life, what does it affect
- decreases osteoclasts by 85% in 3 days
- 1/2 half of denosumab is 25 days
-80% degraded in 2 months - denosumab only affects the RANK ligand
- not incorporated in bone
what does it mean for the pt when the drug is not incorporated into the bone
once they come off the drug theyre good to go
describe the denosumab vacation
- 2 month presurgical holiday: 80% degradation
- average 4 month postsurgical holiday- ideally 8 months
how do you predict complications with MRONJ and describe it
- CTX testing
- measures serum levels of C-terminal telopeptide: metabolite of bone matrix degradation
- marker for osteoclastic activity
- normal is greater than 300. average is 400-550
- 150 or less is at risk for MRONJ
what 3 things are needed for the dx of MRONJ
- current or previous antiresorptive medication therapy
- exposed necrotic bone for longer than 8 weeks
- no history of radiation to the jaws
what is another alternative for MRONJ tx, what does it do and what are the doses
- forteo
- recombinant parathyroid hormone teriparatide
- binds to osteoblasts and promotes proliferation
- daily injections for up to 2 years
- greater than 2 years may lead to osteogenic sarcoma
- expensive - $560 a month
who is forteo used for and who is it contraindicated in
- resolve MRONJ in osteoporotic patients
- may be used to treat osteoporosis
- contraindicated in pts with bone metastases or previous radiation- risk of osteogenic sarcoma
