Radiation Therapy, Oral Cavity Cancer,

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Radiation Therapy,Oral Cavity Cancer, Dental
Care in HN Cancer Patient
John F. Greskovich Jr., M.D.Department of
Radiation OncologyApril 7, 2006
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Oral Cavity Cancer

• Presentation Outline
• Overview of Radiation Therapy
• Oral Cavity Cancer
• Case Presentations /Radiation Planning
• Tissue Effects of Radiation /Dental Concerns
• Whats on the Horizon?

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Principles of Radiation Therapy

• Physics of Radiation Therapy

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Principles of Radiation Therapy

• Discovery of X-rays
• On November 8, 1895, Wilhelm Conrad Roentgen, a
  German physicist, discovered a new kind of ray
  emitted from a gas discharge tube (cathode ray
  tube) when a high voltage discharge was applied.
• Roentgen enclosed the gas discharge tube with
  cardboard so that no light could escape.

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Principles of Radiation Therapy

• Discovery of X-rays
• When Roentgen darkened his laboratory to check if
  any light was escaping, he noted a fluorescence
  on a work bench 3 feet away on paper coated with
  barium platinocyanide.
• Since electrons could not escape the glass tube,
  and no light rays could escape the cardboard, he
  concluded correctly that he had discovered a new
  kind of ray - the X-ray.

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Principles of Radiation Therapy

• Discovery of X-rays
• Roentgen demonstrated his findings in December
  1895, by asking Rudolf Albert van Kolliker, a
  prominent Swiss professor of anatomy, to put his
  hand in the beam, producing the first radiograph.

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Principles of Radiation Therapy

• Discovery of X-rays
• Roentgen was awarded the first Nobel Prize for
  Physics in 1901.

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Principles of Radiation Therapy

• Therapeutic Use of X-rays
• In 1897, Wilhelm Alexander Freud, a German
  surgeon, demonstrated before the Vienna Medical
  Society the disapperance of a hairy mole
  following treatment with X-rays.

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Principles of Radiation Therapy

• Electromagnetic Spectrum
• Typically described as a photon. There is a
  spectrum of electromagnetic radiation with
  energies spanning from low energy radio waves to
  high energy x- and g-rays.

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Principles of Radiation Therapy

• Electromagnetic Spectrum
• Bottom Line
• Ionizing Radiation includes only high energy
  ultraviolet, X-ray, and g-ray radiation.
• Ionizing ? having enough energy to break chemical
  bonds

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Principles of Radiation Therapy

• Radiation Generator
• Linear Accelerator

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Principles of Radiation Therapy

• Radiobiologic Theory Behind Radiation Therapy

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Principles of Radiation Therapy

• Radiobiology
• Radiobiology is the study of the action of
  ionizing radiation on living things.

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Principles of Radiation Therapy

• Radiobiology DNA as Target
• 250 Gy (25,000 rads) given to cytoplasm
  has no effect on cell
  proliferation
• 1-2 alpha particles delivered to nucleus
  can be lethal

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Principles of Radiation Therapy

• Radiobiology DNA as Target
• Evidence of DNA as principle target
• Direct correlation of aberrant chromosomes and
  chromatids with cell death

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Principles of Radiation Therapy

• Radiobiology
• Chromosomal Lethal Damage
• Occurs during G1 of cell cycle
• Examples Acentric, Dicentric, Ring Chromosomes

Cell Cycle
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Principles of Radiation Therapy

• Radiobiology
• Chromosomal (G1) Lethal Damage
• Examples Acentric, Dicentric

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Principles of Radiation Therapy

• Radiobiology
• Repopulation
• Growth of tumor cells between fractions of
  radiation.
• Accelerated repopulation occurs typically around
  day 28 of radiation therapy in HN cancers
  (Withers, 1988).
• Accelerated Fractionation with Concommitant Boost
  starting day 28 has been shown in RTOG 90-03 to
  improve Local Control over standard fractionation
  for locally advanced HN Cancer (2YLC 55 vs 45)

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Principles of Radiation Therapy

• Radiobiology
• Danish HN study shows improved Local Control
  with decreased treatment time

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Oral Cavity Cancer

• Presentation Outline
• Overview of Radiation Therapy
• Oral Cavity Cancer
• Case Presentations /Radiation Planning
• Tissue Effects of Radiation /Dental Concerns
• Whats on the Horizon?

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Oral Cavity Cancer

• HN Cancer Statistics
• Estimated 40,000 cases of HN Cancer will occur
  in the U.S. per year.
• Only one-third of patients present with localized
  HN Cancer which is highly curable with surgery,
  radiation therapy, or a combination of the two.
• One-half of patients present with locoregionally
  advanced or unresectable disease with cure rates
  historically at or below 50.

Simmonds M., CA Cancer J 2003
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Reirradiation for Recurrent HN Cancer
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Reirradiation for Recurrent HN Cancer
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Reirradiation for Recurrent HN Cancer
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Oral Cavity Cancer

• Work-up
• HP (palpation, visualization)
• CT neck
• CT chest (or CXR)
• Panorex

• Triple endoscopy with biopsy
• Blood work including Liver Function Tests, CBC,
  and thyroid panel
• Dental Evaluation

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Oral Cavity Cancer

• Dental evaluation Pre-radiation
• Extraction of non-restorable teeth secondary to
  periodontal disease or caries. DO NOT REMOVE ALL
  TEETH!
• Construct fluoride carriers
• Construct customized mouth pieces or shielding
• Radiation Therapy should be delayed 10-14 days
  to allow gingiva to heal

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Oral Cavity Cancer

• Treatment of Primary

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Oral Cavity Cancer

• Treatment of Primary
• Early Stage Tumors (T1-2)
• Surgery alone or Radiation alone obtain
  approximately same results with respect to
  overall cure.

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Oral Cavity Cancer

• Treatment of Early Stage (T1-2) Primary
  Radiation
• Potential Advantages of Radiation over Surgery

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Oral Cavity Cancer

• Treatment of Early Stage (T1-2) Primary
  Radiation
• Potential Advantages of Radiation over Surgery
• Preservation of normal tissue
• Improved cosmetic result
• Radiation can treat a larger area at risk with
  more generous margins

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Oral Cavity Cancer

• Treatment of Early Stage (T1-2) Primary
  Radiation
• Disadvantages of Radiation
• Unpleasant acute side effects

• Xerostomia
• Dysphagia
• Weight Loss
• Hair loss

• Mucositis
• Oral candidiasis
• Dysgeusia (abnormal taste)
• Fatigue

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Oral Cavity Cancer

• Treatment of Advanced Stage (T3-4) Primary

RTOG 73-03, Kramer, Head Neck Surg 10 49, 1987
Tupchong, IJROBP 20 21, 1991.
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Oral Cavity Cancer

• Treatment of Advanced Stage (T3-4) Primary
• Combined treatment with Surgery and post-op RT
  historically has been standard of care in U.S..
• Post-op RT has been shown to be superior to
  pre-op RT in a randomized study RTOG 73-03.
• Timing Post-op RT is typically started within 6
  wks post-op (Vikram).

RTOG 73-03, Kramer, Head Neck Surg 10 49, 1987
Tupchong, IJROBP 20 21, 1991.
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Oral Cavity Cancer

• Treatment of Advanced Stage (T3-4 or N2-3)
• Currently, in the U.S., a change in philosophy to
  Organ Preservation for locally advanced HN
  Cancer is occurring.
• Locally advanced and unresectable HN cancer
  patients treated with radiation therapy alone
  obtain local-regional control in only 46-55 of
  the cases at 2 years.

Fu et al, RTOG 90-03, IJROBP 48 7, 2000
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Oral Cavity Cancer

• Treatment of Advanced Stage (T3-4 or N2-3)
• Encouraging data demonstrates an improvement in
  survival and local-regional control with the
  addition of chemotherapy to radiation therapy.
• Unfortunately, some 30-50 of locally advanced
  HN cancer patients will die from uncontrolled
  local or regional disease despite aggressive
  chemoradiation or surgery and post-op radiation.

Adelstein et al, Intergroup Study, JCO 21 92,
2003 Brizel et al, NEJM 338 1798, 1998 Calais et
al, GORTEC 94-01, Proc ASTRO 2001 Garden et al,
RTOG 97-03, Proc ASCO 2001
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Oral Cavity Cancer

• Presentation Outline
• Overview of Radiation Therapy
• Oral Cavity Cancer
• Case Presentations /Radiation Planning
• Tissue Effects of Radiation /Dental Concerns
• Whats on the Horizon?

Simmonds M., CA Cancer J 2003
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Oral Cavity Cancer

• Case Study 1
• 39 yr old male with 25 yr history of cigarette
  use (2 packs per day) and intermittent history of
  marijuana use.
• He complains of 2 month history of biting the
  inside of his right cheek
• Physical exam shows bilateral leukoplakia on
  buccal mucosal and no palpable lymphadenopathy

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Oral Cavity Cancer

• Case Study 1
• ENT notes small area of erythroplakia on left
  buccal mucosa
• Bilateral biopsies reveal moderate dysplasia on
  the right buccal mucosa and moderately
  differentiated squamous cell carcinoma on the
  left.
• Multidisciplinary tumor board recommends
  definitive radiation therapy for a 1 cm tumor
  (T1N0 or AJCC stage I) on the left buccal mucosa.

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Oral Cavity Cancer

• Case Study 1
• Patient received definitive, radiation therapy to
  the primary tumor and ipsilateral levels IB, II,
  and III LN stations.
• Primary tumor had a complete response by the end
  of 72 Gy of radiation.
• Patient only had mild xerostomia since
  contralateral salivary glands were spared.

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Oral Cavity Cancer

• Case Study 2
• Patient is a 65 yr old AA male with 3 month
  history of progressive dysphagia, odynophagia.
• Additional symptoms are a 30 lb weight loss, foul
  smelling breath, right ear pain.
• Physical exam shows an obvious large tumor in the
  right oral tongue, measuring 3 cm.

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Oral Cavity Cancer

• Case Study 2
• Physical exam also showed a 3.5cm right
  jugulodigastric lymph node (level II).
• CT of the neck and PET scan document the two
  above clinical findings.
• ENT did triple endoscopy, biopsy of tongue mass,
  and placement of PEG tube.
• Biopsy showed a moderately differentiated
  squamous cell carcinoma.

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Oral Cavity Cancer

• Case Study 2
• He was offered organ preservation with
  chemoradiation or surgery followed by post-op
  radiation.
• Patient refused chemotherapy and opted for
  surgery followed by radiation.
• A partial glossectomy with right modified radical
  neck dissection was performed showing two
  pathologic nodes, and negative but close surgical
  margins.

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Oral Cavity Cancer

• Case Study 2
• Post-op radiation was completed to the bilateral
  neck (levels IB, II, III, IV, V) and tumor bed to
  a dose of 50 Gy.
• The tumor bed was boosted to a final dose of 64
  Gy.

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Oral Cavity Cancer

• Presentation Outline
• Overview of Radiation Therapy
• Oral Cavity Cancer
• Case Presentations /Radiation Planning
• Tissue Effects of Radiation /Dental Concerns
• Whats on the Horizon?

Simmonds M., CA Cancer J 2003
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Oral Cavity Cancer

• Radiation Therapy Acute Effects
• Mucositis
• Oral candidiasis
• Tongue sensitivity
• Decreased taste
• Fatigue

• Xerostomia
• Dysphagia
• Weight Loss
• Hair loss

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Oral Cavity Cancer

• Radiation Therapy Acute Effects
• Dental Recommendations
• No dental prostheses should be worn during
  radiation once irritation, mucositis, or
  ulceration develops.
• Meticulous dental hygeine

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Oral Cavity Cancer

• Radiation Therapy Acute Effects
• Dental Recommendations
• Meticulous dental hygeine
• Frequent brushing (after meals, night)
• Daily flossing
• Daily fluoride gel applications with custom
  carriers

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Oral Cavity Cancer

• Radiation Therapy Acute Effects
• Dental Recommendations
• Meticulous dental hygeine
• Fluoride 1.1 neutral sodium flouride (porcelain
  crowns) or 0.4 stannous fluoride.

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Oral Cavity Cancer

• Radiation Therapy Acute Effects
• Recommendations
• Chlorhexidine mouthwash was shown to be
  detrimental (more discomfort, taste alteration,
  teeth staining) during radiation in a randomized
  trial (Foote et al).
• Baking soda and salt rinses are most beneficial.
• BMX and liquid pain medicines are helpful

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Oral Cavity Cancer

• Radiation Therapy Potential Late Effects
• Permanent Xerostomia / Change in Taste
• Dental caries cariogenic pH from xerostomia
• Soft tissue necrosis
• Bone necrosis (osteoradionecrosis)
• Radiation-induced tumors

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Oral Cavity Cancer

• Radiation Therapy Potential Late Effects
• Dental Interventions
• Frequent, professional dental care may ameliorate
  or prevent demineralization of teeth
• If enamel breakdown, calcium phosphate
  remineralizing gel is used.
• Teeth extractions should be avoided if possible
  especially in regions of bone receiving over 50
  Gy.

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Oral Cavity Cancer

• Radiation Therapy Potential Late Effects
• Dental Interventions
• Prosthodontics are constructed after mucosa is
  healed.
• If teeth extractions are necessary, conservative
  surgery, antibiotic coverage, and possibly
  hyperbaric O2 should be considered.

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Oral Cavity Cancer

• Radiation Therapy Potential Late Effects
• Soft tissue necrosis
• Relatively common
• Typically small, and self-limited
• Must rule out recurrent cancer
• Conservative tx is rule

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Oral Cavity Cancer

• Radiation Therapy Potential Late Effects
• Soft tissue necrosis
• Observation
• Antibiotics (tetracycline)
• Comfort agents viscous lidocaine or BMX
• Hyperbaric O2 is used for larger lesions or bone
  necrosis

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Oral Cavity Cancer

• Radiation Therapy Potential Late Effects
• Osteoradionecrosis
• Dentures discontinued, or modified to decrease
  trauma
• No cases of bone necrosis are reported by Dr.
  Karen Fu if dosebonelt65 Gy
• Risk increases greatly for dose bone gt75 Gy
• Management is conservative (analgesics,
  antibiotics, good hygiene)

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Oral Cavity Cancer

• Radiation Therapy Potential Late Effects
• Osteoradionecrosis
• Hyperbaric O2 is sometimes helpful.
• Surgery is used as a last resort for treatment of
  soft tissue or bone necrosis.

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Oral Cavity Cancer

• Radiation Therapy Potential Late Effects
• Xerostomia
• Dependent on dose (tolerance 32 Gy)
• Dependent on volume of salivary gland tissue
  irradiated (mild if can spare 1 parotid).
• Treatment options pilocarpine post-radiation,
  amifostine concurrent with radiation for
  prevention

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Oral Cavity Cancer

• Radiation Therapy Potential Late Effects
• Muscles of Mastication
• If included in radiation field, fibrosis may
  occur
• Patient should exercise muscles to prevent
  trismus (open/close, open against pressure).

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Oral Cavity Cancer

• Presentation Outline
• Overview of Radiation Therapy
• Oral Cavity Cancer
• Case Presentations /Radiation Planning
• Tissue Effects of Radiation /Dental Concerns
• Whats on the Horizon?

Simmonds M., CA Cancer J 2003
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Principles of Radiation Therapy

• Radiobiology Therapeutic Ratio
• Radioprotection for Normal tissues Amifostine

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Principles of Radiation Therapy

• Radiobiology Therapeutic Ratio
• Radioprotection for Normal tissues Amifostine

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Principles of Radiation Therapy

• Radiobiology Therapeutic Ratio
• Improved Dose-distribution Brachytherapy

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HDR Brachytherapy
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Principles of Radiation Therapy

• Radiobiology Therapeutic Ratio
• Improved Dose-distribution Intensity Modulated
  Radiation Therapy (IMRT)

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SMLC Segments Taken with EPI
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