Principle of Cancer Biology and Therapy Flashcards
(97 cards)
1
Q
What therapies with be utilized?
A
- Surgery
- Radiation
- Chemotherapy
2
Q
What are the types of surgery?
A
- Biopsy/Radical Neck Dissection
- Mandibular resection/graft
- Maxillectomy/oro- antral communication
- Glossectomy
3
Q
How will radiation be delivered?
A
- Fixed Beam Radiation
- Intensity Modulated Radiation Therapy (IMRT)
4
Q
How does fixed beam radiation therapy work?
A
All the tissue between the portals receives the same dose
5
Q
How does intensity modulated radiaiton therapy work?
A
- 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)
6
Q
What is fractionation?
A
The application of radiation therapy in smaller consecutive doses to minimize the lethal effects and limit the side effects of the therapy
7
Q
What is the typical fractionation?
A
The dose is usually administered 5 times a week for 5 to 7 consecutive weeks
8
Q
What are the 5 Rs for fractionation?
A
- Repair
- Redistribution
- Repopulation
- Reoxygenation
- Radiosensitivity
9
Q
What is the repair part of fractionation?
A
- Radiation causes sub-lethal damage to normal and malignant cells
- The repair pathways are often blocked or impaired in the malignant cells resulting in cell death
10
Q
What is the redistribution part of fractionation?
A
- DNA is more sensitive during certain stages of cell replication (G2 and M phases)
— Most stable (S phase) - Fractionation provides multiple opportunities to affect the cells when they are in the sensitive phase
11
Q
What is the repopulation part of fractionation?
A
- 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
12
Q
What is the reoxygenation part of fractionation?
A
- Tumor cells are more resistant to radiation in hypoxic environments
- Fractionation increases the odds that that tumor cells will be in a nutrient field during radiation
- The outermost tumor cells are destroyed exposing the “hypoxic” inner layers of tumor cells
13
Q
What is the radiosensitivity part of fractionation?
A
- 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
14
Q
What should you consider before treatment to radiation in terms of dentistry?
A
- Complete dental/perio evaluation
- Establish a baseline
- Previous dental experience/frequency
- Extract suspect teeth in the radiation field
- Complete prophylaxis and restorative tx
- Fabricate custom fluoride trays
15
Q
What are the indications for extraction prior to radiation therapy?
A
- Non-restorable caries or high caries rate
- Periodontal pocketing > 5mm
- Furcation involvement
- Impacted teeth
16
Q
What are dental complications after radiation?
A
- Xerostomia/Dental Caries
- Mucositis
- Osteoradionecrosis
- Trismus
- Hypogeusia/Dysgeusia
- Nutritional Deficiency
17
Q
Where is saliva produced mainly?
A
- Parotid – serous
- Submandibular – serous/mucous
- Sublingual – primarily mucous
18
Q
Hypofunction of salivary glands can occur when exposed radiation doses as low as ____ Gy
A
25
19
Q
Which is more sensitive to radiation serous glands or mucous glands?
A
serous
20
Q
The rapid formation and progression of dental caries after radiation is mainly attributed to the reduced quality and quantity of the ________
A
saliva
21
Q
What is the treatment for xerostomia after radiation (especially to stop caries)?
A
- WATER!
- Salivary Substitutes
- Minimize carbohydrate and alcohol intake
- Alcohol Free Mouth Rinses (Peridex, Crest Pro Health)
- Listerine
- Sugar-free options
- Xylitol
- sialogogues
- fluoride
22
Q
What is xylitol?
A
- Sugar alcohol originally derived from birch trees
- Commercially produced from corn cobs (xylan)
23
Q
Why is xylitol good for xerostomia/caries after radiation?
A
- Caries causing bacteria are unable to metabolize it
- Ingesting 6-8 grams daily can decreased caries
- Frequency of use more important than quantity
- Available as a packaged sweetener or in gums, mints, candies, and oral rinses
24
Q
How much xylitol in certain brands?
A
- Ice Breakers Ice Cubes – 1g/piece
- Epic gum –1g/piece
- Epic mints – 0.5/piece
- Spry gum –0.72/piece
- Xylimelts – 0.5g/piece
25
What are the issues with xylitol?
- Can cause gastric issues with some pts
--- Primarily when over 50g ingested/day
- Extremely toxic to dogs
26
What are sialogogues?
- Cholinergic agonist
- Pilocarpine hydrochloride
--- 5-10mg tid
--- Max dose 30mg/day
--- May take 12 weeks to see results
27
What is the fluoride therapy for patients after radiation?
- Rinse, brush, floss, fluoride trays
- 10 minutes/day
- No food or drink for 30 minutes
- Best results when used prior to bedtime
28
What are the types of fluoride?
- 1.1% Sodium fluoride
- 0.4% Stannous fluoride
--- Better for root caries
--- May stain the teeth brown
29
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 swallowing.
- The signs and symptoms often arise after the second week of therapy and may last a few weeks after the completion of treatment
30
What are the treatments for mucositis (mild pain)?
| control the symptoms
Mild Pain
- Maintain oral hygiene
- Use bland oral rinses
--- Baking soda/water with/without salt
- Use topical oral pain management
--- Caphosol
--- Magic Mouthwash (Viscous lidocaine, Maalox, diphenhydramine; with/without nystatin)
- Mild analgesics (OTC)
31
What is in magic mouthwash?
- Diphenhydramine 12.5mg/5mL - 1 part (120mL)
- Maalox - 1 part (120mL)
- Viscous Lidocaine 2% - 1 part (120mL)
- Nystatin Susp. 100,000 U/mL - 1 part (120mL)
--- (Optional)
32
What are the treatments for mucositis (moderate pain)?
Moderate pain
- Addition of moderate strength opioids
--- Hydrocodone and oxycodone
- Altered diet (soft)
33
What are the treatments for mucositis (severe pain)?
Severe pain
- Addition of strong opioids
--- Oxycodone, morphine, oxymorphone
- May need nasogastric or PEG tube
34
What is osteoradionecrosis (ORN)?
- Radiation results in vascular changes in the bone limiting the blood supply and the ability to heal after trauma or extractions
- Associated with radiation doses above 50 Gy
- More common with the mandible
35
Osteoradionecrosis (ORN) is associated with radiation doses above ____ Gy
50
36
How do you prevent osteoradionecrosis?
- Extraction of questionable teeth prior to radiation therapy
- Complete root canal therapy if it is an option
- If a post radiation TE is necessary, hyperbaric oxygen (HBO) therapy may be necessary
--- 20 dives prior to TE/10 dives after TE
--- HBO is only needed once in a lifetime, not for each procedure
37
What is stage 0 ONJ?
- No exposed bone, but pt. is symptomatic
- Radiographic changes may be present
38
What is the treatment at stage 0 ONJ?
- Periodic monitoring
- Systemic management (antibiotics and pain meds)
39
What is stage 1 ONJ?
Bone is exposed, asymptomatic, no infection present
40
What is the treatment at stage 1 ONJ?
- Monitor closely for 8 weeks
--- If no changes, continue to monitor quarterly
- Meticulous home care
- Antimicrobial oral rinses
- Remove loose sequestra if present
41
What is stage 2 ONJ?
- Exposed bone with associated pain
- Purulent exudate may be present
42
What is the treatment at stage 2 ONJ?
- Same treatment as Stage 1
--- Addition of systemic antibiotics(Penicillin, Clindamycin, Doxycycline)
-Superficial debridement to relieve soft tissue irritation
- Possible hyperbaric oxygen therapy?
43
What is stage 3 ONJ?
Exposed bone with pain and one of the following:
- Pathologic fracture
- Extra-oral fistula
- Necrotic lesion extends to the inferior border
44
What is the treatment at stage 3 ONJ?
- Surgical debridement or resection
- Antibiotic therapy
- Possible hyperbaric oxygen?
45
What is trismus?
- Primarily occurs when the pterygoid region is irradiated
- Usually noticed near the completion of radiation therapy
- Radiation may cause spasms or fibrosis of the TMJ and muscles of mastication resulting in a limited range of motion
- The effects of trismus usually are not permanent, but may last for several months after the completion of radiation therapy
46
What is the treatment for trismus?
- Warm, moist heat
- Massage
- Physical therapy
--- Tongue depressors
--- TheraBite
--- Dynasplint
47
What is hypogeusia/dysgeusia?
- Permanent taste loss may occur with a cumulative dose of 60 Gy
- At lesser dosages, the taste may return.
- Xerostomia and mucositis may also contribute to the alterations in taste
- May or may not improve depending on the site and amount of radiation
48
Permanent taste loss may occur with a cumulative dose of ____ Gy
60
49
What is the treatment for hypogeusia/dysgeusia?
- Water/salivary substitutes
- Constantly monitor for bacterial or fungal infections
50
What is important to know about making removeable applicances after radiation?
- Wait 6-9 months after the completion of radiation to fabricate dentures and RPDs
- Educate the patient
- Limit the amount of use
- Place silicone liners (GC Reline)
- Set a 3-month recall
51
Wait ______ months after the completion of radiation to fabricate dentures and RPDs
6-9
52
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
53
How is chemo administered?
- IV infusion
--- Port-A-Cath
- Pill
54
What are the dental effects of chemo?
- Immune system suppression
- Mucositis
- Xerostomia
- Bleeding
- Hypogeusia/Dysgeusia
55
What dental treatment should be done before chemo?
- Complete dental examination
- Prophylaxis /SRP
- Extraction of teeth with non-restorable caries, poor periodontal prognosis
- Complete any needed endodontic therapy
56
What dental treatment can be done during chemo?
- 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 treatment is needed, blood counts are usually best just prior to their next course of chemo
57
Can you do any oral surgery during chemo?
- Any invasive procedures (i.e., extractions) get
recent blood counts
--- Absolute Neutrophil Count (ANC) ->1000/mm3
--- Platelet count - >75,000/mm3
58
When should antibiotic prophylaxis be considered for chemo patients?
- Presence of a Port-A-Cath
- Neutrophils between 1,000 and 2,000/mm3
59
Chemo leads to immunosuppresion. How can you prevent this?
- Prevention is key
--- Brush and floss
--- Chlorhexidine rinse (non-alcohol)
--- Neutral rinse (baking soda and water)
- Treat opportunistic infections
--- Fungal (Candida)
---Nystatin, Fluconazole
--- Viral (Herpetic)
--- Acyclovir, Famciclovir
60
How is mucositis treated for patients on chemo?
the same as for radiation
61
What is important to know about xerostomia for patient's after chemo?
- Xerostomia usually resolves within a few months after treatment is completed
- Xerostomia can provide the ideal environment of opportunistic infections
62
What is the treatment for xerostomia for patients on chemo?
- Water, Water, Water
- Salivary substitutes
- Sugar-free or xylitol gum
- Monitor carbohydrate intake
- Sialogogues (pilocarpine)
63
What should you be aware of with bleeding and chemo?
- Chemotherapy can drastically decrease the platelet count
- Avoid invasive dental procedures if at all possible
- Gentle brushing and flossing
64
What is important to know about hypogeusia/dysgeusia during chemo?
- The effects are usually temporary.
- Effects may be related to other complications:
--- Mucositis
--- Xerostomia
--- Bacteria or fungal infections
65
What are antiresorptive medications?
- Bisphosphonates
- RANK Ligand Inhibitors
66
What are bisphosphonates?
- Initially used for the treatment of osteoporosis, Paget’s disease, and osteogenesis imperfecta
- More recently, they have been used as an
adjunctive treatment of cancer
- Decrease osteoclastic activity
67
What are the features of bisphosphonates (non-nitrogen)?
- Oral only
--- Etidronate – Didronel
---Clodronate –Bonefos, Clasteon, Loron
- Primarily used for the treatment of Paget’s disease
- Low potency
- Prevents osteoclast proliferation by inhibiting ATP dependent enzymes
68
What are the features of bisphosphonates (nitrogen containing)?
- Oral or IV
- Mechanism of action
--- Prevents binding of essential proteins to the cell membrane leading to apoptosis
--- Prevents adhesion of the osteoclasts to the hydroxyapatite crystals by altering the cell cytoskeleton
69
What are the features of oral nitrogen containing bisphosphonates?
- Approved for use in the treatment of Paget’s disease and osteoporosis
--- Alendronate (Fosamax)
--- Risedronate (Actonel)
--- Ibandronate (Boniva)
70
What are the features of IV nitrogen containing bisphosphonates?
- Used in the treatment of osteoporosis
--- Zolendronate (Reclast) – 5mg/year
- Used in the treatment of bone metastases
--- Zolendronate (Zometa) – 4mg/3 weeks
--- Pamidronate (Aredia) – 90mg/3 weeks
71
What are the features of antiresorptive agents?
- Denosumab (Monoclonal antibody)
--- Osteoporosis – Prolia – 60mg/6 months
--- Bone Metastases –Xgeva –120mg/4 weeks
- Mechanism of action
--- Tumor cell promote the release of RANK Ligand from the osteoblast within turn promote the production of osteoclasts
--- Denosumab binds to the RANK Ligand an prevents osteoclast proliferation
72
What med are associated with ARONJ/BRONJ?
Antiresorptive Medications
73
What med are associated with MRONJ?
antiangiogenic medications
74
What are the antiangiogenic medications?
- Tyrosine kinase inhibitor
--- Sunitinib (Sutent)
---Sorafenib (Nexavar)
- Humanized monoclonal antibody
--- Bevacizumab (Avastin)
75
What is the mechanism of action of antiangiogenic medications?
- Recognizes and blocks vascular endothelial growth factor (VEGF), a protein necessary for angiogenesis
- Used in the treatment of gastrointestinal tumors, renal cell carcinomas, and neuroendocrine tumors
76
What are the widespread risk factors of MRONJ
- Potency
--- Oral non-nitrogen containing bisphosphonates
--- Oral nitrogen containing bisphosphonates (0.4% to 4%)
--- IV bisphosphonates (4% to 12%) (Aredia, Zometa)
--- XGEVA
--- IV bisphosphonates plus an antiangiogenic medication
- Duration
--- Increased risk after 18 months
77
What are the local risk factors of MRONJ
- Surgery/trauma
--- Dental extractions
--- Osseous surgery (periodontal, apicoectomy)
--- Implant placement
- Anatomy
--- Mandible vs. Maxilla (2:1 ratio)
--- Tori, exostoses
--- Mylohyoid ridge
78
What are the demographic factors for MRONJ?
- Age
--- 9% increased risk of MRONJ with each passing decade
- Race
--- Caucasian
79
What are the systemic factors of MRONJ?
- Primary cancer diagnosis
--- Multiple myeloma –highest risk
--- Breast cancer –2nd highest risk
- Concurrent osteopenia or osteoporosis diagnosis
80
What should you do for a patient before starting antiresorptive meds?
- Extract non-restorable and questionable teeth along with alveoplasty, tori removal, etc.
- Complete necessary periodontal therapy
- Complete any endodontic and restorative work
81
What should the patient do with removeable appliances while on antiresorptive meds?
- Limit the amount of use
- Place silicone liners if necessary (GC reline)
- Educate the patient
- 3-month recall intervals
82
If any surgery or invasive procedures are necessary, a 3 month ________ should be completed prior to therapy and use of the antiresorptive/antiangiogenic agents should not be started again until after osseous healing has occurred
“drug holiday”
83
____% of the bisphosphonate is excreted by the kidneys within hours of ingestion or infusion
50%
| Remaining 50% deposited in the skeleton
84
85
What are the features of osteocytes in terms of bisphosphonates?
- Make up 85% of resting bone
- Have a long life span
- Have a low affinity for bisphosphonates
- Bisphosphonates loosely bind to the surface and are removed within days
| these aren't a problem for the alt approach to drug holiday
86
What are the features of osteoclasts in terms of bisphosphonates?
- 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
| these aren't a problem for the alt approach to drug holiday
87
What are the features of osteoblasts in terms of bisphosphonates?
- Make up 10-12% of resting bone
- Have a life span of 2 months
- 4x the affinity for bisphosphonates
- Bisphosphonates are incorporated into the bone instead of being released
| these ARE the problem
88
Because of osteoblasts...
- Bisphosphonates are primarily distributed in areas of active bone remodeling
- Stem cell development into osteoclasts minimized
- Increase in osteoclast apoptosis
89
In __________ areas, an increase in bisphosphonates disrupts the synergistic makeup of the basic multicellular unit (BMU)
remodeling
90
What is the alternative to a drug holiday?
2 month presurgical holiday
- Osteoclasts are the only reservoir for the
bisphosphonates
--- Allows for 4 life cycles
- Minimal remaining bisphosphonate
Average 4 month postsurgical holiday (ideally 8 months)
- Necessary time needed for bones to return to “resting” state
- No needed alteration in bisphosphonate therapy if planned correctly
91
What is important about denosumab and the body?
- Osteoclasts decreased by 85% in 3 days
- ½ life of denosumab is 25 days
--- 80% degraded in 2 months
- Denosumab only affects the RANK ligand
--- Not incorporated in the bone
92
What is the denosumab vacation?
- 2 month presurgical holiday
--- 80% degradation
- Average 4 month postsurgical holiday (ideally 8 months)
---No needed alteration in denosumab therapy if planned correctly
93
What is CTX testing?
- Measures serum levels of C-terminal telopeptide
--- Metabolite of bone matrix degradation
-Marker for osteoclastic activity
- Normal is >300 (average 400-550)
- 150 or less is at risk for MRONJ
94
What are the 3 things you need to diagnose MRONJ?
- Current or previous antiresorptive medication therapy
- Exposed necrotic bone for longer than 8 weeks
- No history of radiation to the jaws
95
What are the stages and treatments for MRONJ?
the same as for radiation (ONJ)
96
What is forteo?
| alternative treatment
- Recombinant parathyroid hormone teriparatide
- Binds to osteoblasts and promotes proliferation
- Daily injections for up to 2 years
--- > 2 years of use may lead to osteogenic sarcoma
- Expensive ($560/month)
97
What is important to know about forteo?
- Resolve MRONJ in osteoporotic patients
- May be used to treat osteoporosis
- Contraindicated in pts. with bone metastases or previous radiation (risk of osteogenic sarcoma)
