Download Radiation Oncology

Radiation Oncology: Principles of
Therapy and Treatment-Related
Toxicity
HOPA 2010
BCOP RECERTIFICATION
Learning Objectives
Radiation Oncology:
Principles of Therapy and
Treatment-Related Toxicity
Sally Yowell Barbour, PharmD, BCOP, CPP
Clinical Oncology Pharmacist
Duke University Comprehensive Cancer Center
Durham, North Carolina

Categorize the different types of radiation
therapy available and discuss in what
clinical scenarios they are used
Examine the most common side effects
seen in patients undergoing radiation
therapy
Develop supportive care plans based on
available data for patients undergoing
radiation therapy
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Principles of Radiation Oncology
What is Radiation Oncology?
 Dose measured in Gray (Gy)
• Energy absorbed/Mass of tissue (joules/kg)
• Older terminology is rad
• 1Gy=100rad
 Types of Radiation
•
•
•
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Photons
Electrons
Protons
Neutrons
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97; Camphausen, KA,
Coia, LR. Principles of Radiation Therapy. In: Cancer Management: A Multidisciplinary Approach. 2008:11-22..
Principles of Radiation: Sources of
Radiation
 Radioisotope
• Constant emission
 Linear accelerator
• Radiation only generated when turned on
• Collimators and wedges used to
conform/shift beam
Principles of Radiation: Cell Death
 Free radicals produced
 Target DNA
• Double helix breaks
• DNA damage
 Death
• Apoptosis
• Loss of cellular
reproductive capacities
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97; Camphausen, KA,
Coia, LR. Principles of Radiation Therapy. In: Cancer Management: A Multidisciplinary Approach. 2008: 11-22.
Hellman S. Principles of Cancer Management: Radiation Therapy. In: Cancer: Principles & Practice of Oncology. 2001:265-288.
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97; Camphausen, KA,
Coia, LR. Principles of Radiation Therapy. In: Cancer Management: A Multidisciplinary Approach. 2008: 11-22.
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Radiation Oncology: Principles of
Therapy and Treatment-Related
Toxicity
Principles of Radiation: Fractionation
 Division of total prescribed dose into
smaller doses
• Preferentially spares normal tissue
• Allows total higher doses and increased cell
kill
• Allows for tumor repopulation due to
extension of treatment time potentially
negatively impacting cell kill
• Standard 1.8-2 Gy/day
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97;
Hellman S. Principles of Cancer Management: Radiation Therapy. In: Cancer: Principles & Practice of Oncology. 2001:265-288.
Principles of Radiation: Tumor Control
and Complications
HOPA 2010
Principles of Radiation: Fractionation
 Hyperfractionation
•
•
•
•
Smaller doses decrease normal tissue injury
Multiple doses/day (eg, 1.2Gy BID)
Doses at least 6 hours apart
Common uses: head and neck cancer, small cell
lung cancer
 Hypofractionation
• Fractions > 2Gy/day
• Reduced repopulation and treatment time
• Common uses: metastases
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97;
Hellman S. Principles of Cancer Management: Radiation Therapy. In: Cancer: Principles & Practice of Oncology. 2001:265-288.
Radiosensitivity of Organs
and Tissues
 Early responding tissue
• Quick response but also rapid repopulation and recovery
• High cell turnover at baseline
• Toxicity occurs rapidly and recovery is quick
• Examples: GI mucosa and bone marrow
 Late responding tissue
• Dormant or slow cycling cells
• Better able to repair DNA damage but not large reserve of
stem cells to regenerate tissues
• Toxicity late and often permanent
• Examples: peripheral nerves, kidneys, spinal cord
Hellman S. Principles of Cancer Management: Radiation Therapy. In: Cancer: Principles & Practice of Oncology. 2001:265-288.
Radiosensitivity of Organs
and Tissues
 Parallel structures
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97.
Radiosensitivity of Organs and Tumor
Types
Sensitivity
Tumors
Organs
• Able to tolerate large doses to small volume
Most sensitive
because organ can still function
• Low doses to large volume decreases
function (e.g., lung, liver, kidney)
Moderately
sensitive
Lymphoma
SCLC
Rectal
Breast
NSCLC
Germ cells
Bone marrow
Lung
Kidney
Bowel
Skin
CNS
Connective
tissues
 Serial structures
• Require coordination of all cells to function
properly
• Damage to small volumes can cause
significant injury (eg, spinal cord, bowel)
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97.
Least sensitive
Melanoma
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97.
SCLC=small cell lung cancer, NSCLC=non-small cell lung cancer, CNS=Central Nervous System
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Radiation Oncology: Principles of
Therapy and Treatment-Related
Toxicity
HOPA 2010
Principles of Radiation:
Treatment Planning
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Types of Radiation Therapy (RT)
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CT and simulation
Beam dosimetry
Patient positioning
Target definition
Field design
Dose calculation
External Beam
Internal
Systemic Radiation
Newer Approaches
• Hyperthermia
• Radioimmunotherapy
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97;
Camphausen, KA, Coia, LR. Principles of Radiation Therapy. In: Cancer Management: A Multidisciplinary Approach. 2008: 11-22.
Examples of External Beam RT
Site
Stage
Therapy
Brain
High-grade
astrocytoma
Surgery concurrent
chemo-RT to 60Gy
Head and Neck
Early stage, N0
Advanced
Surgery or RT to 64-70Gy
Chemo-RT to 70Gy or
surgery  chemo-RT to
60-66Gy
Breast
Early T1-2, N0
Advanced T3 or N+
Esophageal
Surgery, 60Gy to breast,
hormones +/- chemo
Surgery chemo RT to
60Gy
Examples of External Beam RT
Site
Lung
Stage
Early T1-2, N0
Advanced, N2+
Rectal
Therapy
Surgery or RT 60-70Gy
Preop chemo + RT 40-50 Gy or
definitive chemo-RT to 60-70Gy
Preop chemo-RT to 50Gy
Hodgkins
Disease
Stage I-II
ChemoRT 20-30Gy to field
NHL
Stage I-II
ChemoRT 30Gy to field
Preop chemo-RT to 50Gy
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97.
RT=radiation therapy
External Beam Radiation
 3D Conformal Radiation
 Intensity-Modulated Radiation Therapy
(IMRT)
 Intraoperative Radiation Therapy
 Stereotactic Radiosurgery
 Stereotactic Body Radiation
 Total Body Irradiation
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97.
3D Conformal Radiation
 Utilizing CT simulator during the planning to allow
geometric shaping of the radiation beam to
conform with beam’s eye view of tumor
• Prostate cancer
Images courtesy of Chris Kelsey, MD
Camphausen, KA, Coia, LR. Principles of Radiation Therapy. In: Cancer Management: A Multidisciplinary Approach. 2008: 11-22.
3
Radiation Oncology: Principles of
Therapy and Treatment-Related
Toxicity
HOPA 2010
Intensity-Modulated Radiation Therapy
(IMRT)
Mesothelioma
IMRT- used to avoid the heart
 Technique to treat irregular or concave
targets with radiation therapy
 Especially useful for tumors in close
proximity to critical normal structures (eyes,
heart, etc.) or not well separated from
normal tissues
• Mesothelioma
• Pituitary Adenoma
Camphausen, KA, Coia, LR. Principles of Radiation Therapy. In: Cancer Management: A Multidisciplinary Approach. 2008: 11-22.
Pituitary Adenoma
IMRT- Used to spare the temporal lobes of the brain
Image courtesy of Chris Kelsey, MD
Intraoperative Radiation Therapy
 Used for inaccessible lesions
• Advanced rectal cancer
• Retroperitoneal sarcoma
 Administering a single, large
dose of radiation therapy to a
tumor in the operating room after
the surgeon has displaced critical
organs
 Doses usually 10-20Gy
 Most common toxicity:
neuropathy
Image courtesy of Chris Kelsey, MD
Stereotactic Radiosurgery
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97.
Stereotactic Radiosurgery
Brain Metastasis- 24Gy X 1
 Single, very large but tightly focused radiation
treatment, to a small tumor in the brain
• Metastases
• Meningiomas
• Pituitary adenomas
 Dose usually 12-24Gy
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97;
Camphausen, KA, Coia, LR. Principles of Radiation Therapy. In: Cancer Management: A Multidisciplinary Approach. 2008: 11-22.
Image courtesy of Chris Kelsey, MD
4
Radiation Oncology: Principles of
Therapy and Treatment-Related
Toxicity
HOPA 2010
Stereotactic Body Radiation
Total Body Irradiation (TBI)
 Used with chemotherapy as preparative
regimen for SCT
 Purpose of RT
 3-5 high-dose
radiation treatments to
tumors
• Stage I lung cancer
• Eliminates disease in sanctuary sites
• Suppresses host immune system
• Ablates native marrow to allow engraftment
 example: 12Gy X 4
• Metastatic tumors
• Meningiomas
 Dose usually 5-20Gy
in 3-5 fractions
Image courtesy of Chris Kelsey, MD
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97.
 Ablative doses 12-17Gy for allo or auto
 Non-myeloablative doses 2Gy as single
dose
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97.
SCT=Stem Cell Transplant
Internal: Brachytherapy
Systemic Radiation
 Iodine-131
• Used after surgery for thyroid cancer;
 Radioactive sources into or adjacent to a tumor
deliver low-energy radiation with limited
penetration
• Cervical cancer
• Sarcoma
• Prostate cancer
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97;
Camphausen, KA, Coia, LR. Principles of Radiation Therapy. In: Cancer Management: A Multidisciplinary Approach. 2008: 11-22.
Images courtesy of Chris Kelsey, MD
selectively absorbed by differentiated
thyroid cells
• Attached to MIBG selectively absorbed by
neuroendrocrine tumors
 Strontium-89 and samarium-153
• Used for bone metastasis
 Radiopharmaceuticals
• Targeted therapies for lymphoma
Koontz BF, Willett CG. Principles of Radiation Oncology. In: Oxford American Handbook of Oncology. 2009:79-97.
MIBG=metaiodobenzylguanidine
BCOP RECERTIFICATION
Acute Effects of Radiation Therapy
Prevention and Management of
Acute and Late Side Effects of
Radiation Therapy
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Mucositis
Taste changes
Dysphagia
Xerostomia
Nutrition
Hearing changes
Desquamation
Dermatitis
Esophagitis
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Pneumonitis
Nausea/vomiting
Proctitis
Cystitis
Pain
Infection
Fatigue
Cytopenias
5
Radiation Oncology: Principles of
Therapy and Treatment-Related
Toxicity
HOPA 2010
Late Effects of Radiation Therapy
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Trismus
Osteoradionecrosis
Xerostomia
Dental caries
Hypothyroidism
Fibrosis
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Case: Head and Neck Cancer
 JH is a 47-year-old female recently
diagnosed with head and neck cancer.
She is scheduled to receive definitive RT
for her early stage disease.
CNS effects
Infertility
Musculoskeletal
Lymphedema
Radiation recall
Secondary
malignancy
Question: The most common radiation related
side effects in a patient with head and neck
cancer are:
A.
Mucositis, vomiting, dermatitis and taste changes
B.
Mucositis, taste changes, hypothyroidism and cytopenias
C.
Mucositis, dermatitis, xerostomia and hypothyroidism
D.
Mucositis, hypothyroidism, cytopenias and xerostomia
Question: Which of the following may reduce
the incidence of xerostomia with radiation
therapy?
A.
B.
C.
D.
The use of 3-D conformal radiation
The use of IMRT
Amifostine administration before radiation therapy
Pilocarpine administration before radiation therapy
Acute Effects of Radiation Therapy
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Mucositis
Taste changes
Dysphagia
Xerostomia
Nutrition
Hearing changes
Desquamation
Dermatitis
Esophagitis
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Pneumonitis
Nausea/vomiting
Proctitis
Cystitis
Pain
Infection
Fatigue
Cytopenias
Xerostomia
 Complaints of dry
mouth
 Decreased saliva
 Fissures in lips
 Dysarthria
 Dysgeusia (taste
alterations)
 Burning sensation of
tongue
 Severity dependent on
• Volume of salivary
•
•
•
•
•
glands in treatment
field
Total dose
Concurrent
chemotherapy
Modality of RT used
Use of
radioprotectants
Other medications
Berk et al. J Support Oncol 2005; 3:191-200.
6
Radiation Oncology: Principles of
Therapy and Treatment-Related
Toxicity
Xerostomia: Saliva
 Saliva flow regulated by CNS
 3 major glands
• Parotid, submandibular and sublingual
• Provide most of saliva in response to exogenous
stimulus
 Minor glands provide daily lubrication
 Flow rates
• Normal- 0.3-0.5 mL/min
• Xerostomia- <0.1 mL/min
 Functions: lubrication, digestion, buffer, etc.
Berk et al. J Support Oncol 2005; 3:191-200.
Prevention of Xerostomia
 3-D conformal radiation
 IMRT
• May allow sparing of parotid glands without
HOPA 2010
Mechanism of Radiation Induced
Salivary Gland Damage
 Exact mechanism is unknown
 Studies show rapid decrease in saliva
during first 2 weeks of RT
 Parotid glands lose more function than
other salivary glands
 Damage to salivary glands impacts salivary
function, swallowing and taste
 Altered volume, consistency and pH 
thick, tenacious, increased acidity
Blanco AI, Chao C. Management of Radiation-Induced Head and Neck Injury. In: Radiation Therapy-A Practical
Guide. 2006:23-41; Guchelaar HJ et al. Support Care Cancer 1997; 5 :281–288
Prevention of Xerostomia: Amifostine
 Brizel et al.
• Landmark trial-Phase III, randomized, placebocontrolled of amifostine
any compromise in local control
 Pharmacologic agents
• Amifostine
• Pilocarpine
 Salivary gland transplant (clinical trial only)
Copyright © American Society of Clinical Oncology
Blanco AI, Chao C. Management of Radiation-Induced Head and Neck Injury. In: Radiation Therapy-A Practical
Guide. 2006:23-41; GIchelaar HJ et al. Support Care Cancer 1997; 5 :281–288; Garden AS et al. Current Oncology
Reports 2006, 8:140–145
Prevention of Xerostomia: Amifostine
 Primary endpoints
• Incidence of grade 2 acute xerostomia
• Grade 3 acute mucositis
• Grade 2 late xerostomia
 Results
• Reduced incidence of significant acute xerostomia
from 78 to 51%
• Reduced incidence of significant chronic
xerostomia at 12 months from 57 to 34%
Brizel, DM et al. J Clin Oncol 2000; 18:3339-3345.
Prevention of Xerostomia:
Amifostine
 Concurrent chemoradiotherapy benefit
• 4 randomized trials with conflicting results
 2 trials including 89 total patients receiving RT
with carboplatin noted significant reduction in
xerostomia and reduction in mucositis
 Small study of 56 patients found reduction in
xerostomia but not mucositis
 MC, DB, PC trial with 132 patients found no
benefit in early or late xerostomia or mucositis
• No impact on mucositis or tumor control at 2 years
Antonadou, D et al. Int J Radiat Oncol Biol Phys 2002; 52:739; Buntzel, J et al. Ann Oncol 1998; 9:505; Buentzel et al. Int
J Radiat Oncol Biol Phys 2006; 64:684
MC=mulitcenter, DB=double blind, PC=placebo controlled
Brizel, DM et al. J Clin Oncol 2000; 18:3339-3345.
7
Radiation Oncology: Principles of
Therapy and Treatment-Related
Toxicity
HOPA 2010
General Treatment of Xerostomia
Prevention of Xerostomia: Amifostine
 Alternative dosing
• 500 mg subcutaneously 20 minutes pre-RT
• More convenient, less expensive and
potentially fewer adverse effects
 Good oral care
 Avoid drugs that can increase or exacerbate
xerostomia
 Modified diet and fluid intake
 Artificial saliva
 Sialagogues
• Bitter/acidic substances
• Sweet-hard candies
 Pharmacologic agents: pilocarpine, cevimeline
Koukourakis, MI et al. J Clin Oncol 2000; 18:2226; Anne PR et al. Int J Radiat Oncol Biol Phys 2007; 67:445.
Blanco AI, Chao C. Management of Radiation-Induced Head and Neck Injury. In: Radiation Therapy-A Practical Guide. 2006:23-41
Summary of Recommendations:
Prevention of Xerostomia
Treatment of Xerostomia: Pilocarpine
 207 patients had received 40Gy to head
and neck randomized to pilocarpine vs.
placebo
 Results (pilocarpine vs placebo)
• Improvement in oral dryness (44 vs 25%)
• Improvement in speech (33 vs 18%)
• Mouth/tongue comfort (31 vs 10%)
 ASCO guidelines (2008)
• Amifostine may be considered to decrease the incidence of
acute and late xerostomia in patients undergoing fractionated
RT alone for head and neck cancer
• Current data do not support the routine use of amifostine with
concurrent platinum-based chemoradiotherapy for head and
neck cancer
 Recommended dose
• 200 mg/m2/day, given as a slow IV push over 3 minutes, 15
to 30 minutes before each fraction of radiation therapy
 Side effects: predominantly sweating
 Dose: 5-10 mg PO TID
Johnson, JT et al. N Engl J Med 1993; 329:390; Guchelaar HJ et al. Support Care Cancer 1997; 5 :281–288
• Insufficient data to support preserved efficacy with other
dosing/routes
Hensley et al. J. Clin Oncol, Vol 27, No 1 (January 1), 2009: pp. 127-145
Oral Mucositis
 Erythema, inflammation, pain and ulceration
 Onset usually 2 to 3 weeks after starting RT
 Incidence/Severity dependent on:
•
•
•
•
Field
Total dose
Duration of RT
Concomitant chemotherapy
 Effect on treatment
• May be dose limiting toxicity
• May lead to unplanned delays/breaks in therapy
Blanco AI, Chao C. Management of Radiation-Induced Head and Neck Injury. In: Radiation Therapy-A Practical
Guide. 2006:23-41
Mucositis: Prevention/Treatment
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Sucralfate
Chlorhexidine
GM-CSF and G-CSF
Glutamine
Amifostine
Benzydamine
Zinc sulfate
Keratinocyte growth
factor (KGF or
palifermin)
 Benzocaine HCl (Oratect®)
 Bioadherent oral gel
(Gelclair®)
 Calcium phosphate mouth
rinse (Caphosol®)
 Topical anesthetics and
antibiotics
 Artificial saliva
 Helium-neon laser therapy
Blanco AI, Chao C. Management of Radiation-Induced Head and Neck Injury. In: Radiation Therapy-A Practical
Guide. 2006:23-41
8
Radiation Oncology: Principles of
Therapy and Treatment-Related
Toxicity
Mucositis: Prevention/Treatment
 Sucralfate mouthwashes
• Placebo-controlled trials have shown no benefit in preventing
or decreasing pain
 Chlorhexidine
• No decrease in incidence, severity or time to resolution of
mucositis
 GM-CSF or G-CSF
• Pilot studies of subcutaneous or topical administration of GMCSF reduced severity of mucositis
• 3 of 4 randomized trials showed no benefit
• 1 positive trial (41 patients) with subcutaneous GCSF
 Glutamine
• Small pilot studies suggest benefit
• Not recommended by MASCC or ISOO
MASCC=Multinational Association of Supportive Care in Cancer; ISOO=International Society of Oral Oncology
HOPA 2010
Mucositis: Prevention/Treatment
 Amifostine
• Benefit not established
• ASCO does NOT recommend for mucositis
 Benzydamine
• NSAID oral rinse (15 mL x 2 minutes 4-8
times daily)
• Reduction in ulceration and delay to use of
systemic analgesics in conventional RT
• MASCC and ISOO recommend for
prophylaxis (>50Gy)
Keefe DM, et al. Cancer 2007 Mar 1;109(5):820-31; Hensley et al. J. Clin Oncol, Vol 27, No 1 (January 1), 2009: pp.
127-145
Mucositis: Palifermin
Mucositis: Palifermin
 Phase II trial
• 99 patients
• Assess the efficacy and safety of palifermin in patients receiving
 Results
• 66 patients received palifermin and 32 received placebo
• Median duration of grade >/= 2 mucositis was 6.5 and 8.1
weeks in the palifermin and placebo groups (P = .157)
• Palifermin appeared to reduce mucositis, dysphagia, and
xerostomia during hyperfractionated radiotherapy (n = 40) but
not standard radiation therapy (n = 59)
 Conclusion
• Well tolerated
• Palifermin did not reduce the morbidity of concurrent
chemotherapy and radiotherapy
• Future studies should evaluate higher palifermin doses with
longer and more standardized assessment of acute mucositis
concurrent chemoradiotherapy for advanced head and neck
squamous cell carcinoma
 Treatment
• Standard RT (daily 2Gy fractions to 70Gy) or hyperfractionated
RT (1.25Gy fractions twice daily to 72Gy) both over 7 weeks
• Chemotherapy included cisplatin 20 mg/m2 for 4 days and
continuous-infusion fluorouracil 1,000 mg/m2/d for 4 days on
weeks 1 and 5 of irradiation
• Randomly assigned 2:1 to palifermin 60 mcg/kg or placebo once
weekly for 10 doses
Brizel, DM, et al. J Clin Oncol 2008; 26:2489
Brizel, DM, et al. J Clin Oncol 2008; 26:2489
Summary of Recommendations: Prevention
and Treatment of Oral Mucositis
 Prevention
• Recommended
 Use of midline radiation blocks and 3-dimensional radiation
treatment to reduce mucosal injury
 Benzydamine for prevention of radiation-induced mucositis in
patients with head and neck cancer receiving moderate-dose
RT
• Not Recommended
 Chlorhexidine
Antimicrobial lozenges
 Amifostine
 Palifermin
GM-CSF
 Treatment
• Sucralfate should not be used for the treatment of radiationinduced oral mucositis
Keefe DM, et al. Cancer 2007 Mar 1;109(5):820-31; Hensley et al. J. Clin Oncol Vol 27, No 1 (January 1), 2009: pp. 127-145
Dermatitis
 RT impairs cell division
 Exacerbated by concurrent chemotherapy/targeted therapy
agents
 Onset: approximately 3 weeks after initiation of RT
 Stages: erythema, hyperpigmentation, dry and moist
desquamation
 Management
• Careful cleansing
• Hydrophilic moisturizers
• Preventing irritation of skin
• Pain management
Blanco AI, Chao C. Management of Radiation-Induced Head and Neck Injury. In: Radiation Therapy-A Practical
Guide. 2006:23-41; Bernier et al. Annals of Oncology 2008 19(1):142-149
9
Radiation Oncology: Principles of
Therapy and Treatment-Related
Toxicity
HOPA 2010
Consensus Guidelines for Management of Radiation
Dermatitis and Coexisting EGRF Inhibitor Rash in
Patients with Squamous Cell Cancer of Head and Neck
 Prophylaxis: none
 Management
• General
 Institutional policy for skin prep before RT
 Topical approaches
• Grade 1
 No specific treatment recommended
 Follow published general guidelines for EGFR inhibitor rash
• Grade 2 and higher
 Follow recommendations for radiation dermatitis
 Grade 2-3: Clean, topical applications, antibiotics if
superinfection; assess weekly
 Grade 4: Require specialized wound care
Nausea/Vomiting
 High risk (>90%)
• Total-body irradiation
 Moderate emetic risk (60-90%)
• Upper abdomen (intermediate risk) hemibody irradiation,
upper abdomen, abdominal-pelvic, mantle, craniospinal
irradiation, and cranial radiosurgery
 Low emetic risk (30-60%):
• Lower thorax, cranium (radiosurgery), and craniospinal
 Minimal emetic risk (<30%)
• Radiation of breast, head and neck, cranium, and extremities
NCCN. Antiemesis. v.4.2009. Available at: http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf; Kris et al. J Clin
Oncol, Vol 24, No 18 (June 20), 2006: pp. 2932-2947
Bernier et al. Annals of Oncology 2008 19(1):142-149
Summary of Guideline
Recommendations: Radiation Induced
Nausea/Vomiting
 High risk:
• 5-HT3 serotonin receptor antagonist with or without a
corticosteroid before each fraction and for at least 24 hours
after
 Moderate risk:
• 5-HT3 serotonin receptor antagonist before each fraction
 Low risk:
• 5-HT3 serotonin receptor antagonist before each fraction
 Minimal risk:
• As-needed basis only
• Dopamine or serotonin receptor antagonists are advised
• If needed, anti-emetics should be continued prophylactically
for each remaining radiation treatment day
Case: Head and Neck Cancer
 JH is a 47-year-old female recently
diagnosed with head and neck cancer.
She is scheduled to receive definitive RT
for her early stage disease
 Possible long-term side effects from
radiation therapy expected in JH are:
NCCN. Antiemesis. v.4.2009. Available at: http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf; Kris et al. J Clin
Oncol, Vol 24, No 18 (June 20), 2006: pp. 2932-2947
Late Effects of Radiation Therapy








Trismus
Osteoradionecrosis
Xerostomia
Dental caries
Hypothyroidism
Fibrosis
Ulceration
Stricture







Obstruction
CNS effects
Infertility
Musculoskeletal
Lymphedema
Radiation recall
Secondary
malignancy
Hypothyroidism
 Most common long-term complication of head
and neck RT
• Incidence varies in studies 14-67%
• Dependent on area radiated, dose and time
• Develops median of 1.4 to 1.8 years (range 0.3-7.2
years)
 Most primary hypothyroidism
 Monitor TSH and free T4 every 6-12 months
 Replacement therapy as indicated
Mercado, G et al. Cancer 2001; 92:2892; Tell, R, et al. Int J Radiat Oncol Biol Phys 2004; 60:395.
10
Radiation Oncology: Principles of
Therapy and Treatment-Related
Toxicity
HOPA 2010
Osteoradionecrosis
 Long-term effects secondary to xerostomia and other RT
effects
 Mandible most affected
 Due to hypocellular and hypovascular changes to bone
 Progressive erythematous changes lead to ulcer and
exposed necrotic bone
 Can cause pain and fracture
 Risk factors
• Pre-existing poor dentition
• Nutritional or immunological compromise
• Smoking during RT
Jereczek-Fossa, BA et al. Cancer Treat Rev 2002; 28:65.
Osteoradionecrosis: Management
 Meticulous
oral/periodontal hygiene
 Replace or increase
salivary flow
 Avoid sucrose-containing
products
 Prompt evaluation of oral
infections
 Optimal nutrition
 Antibiotics
 Hyperbaric oxygen
therapy treatments
 Surgical resection
Jereczek-Fossa, BA et al. Cancer Treat Rev 2002; 28:65.
Additional Acute Effects of Radiation
Therapy

















Mucositis
Taste changes
Dysphagia
Xerostomia
Nutrition
Hearing changes
Desquamation
Dermatitis
Esophagitis
Pneumonitis
Nausea/vomiting
Proctitis
Cystitis
Pain
Infection
Fatigue
Cytopenias
Esophagitis
 Acute symptoms of dysphagia, odynophagia, substernal
discomfort
• Onset 2-3 weeks
 Clinical manifestations of late toxicity: dysphagia, chronic
ulceration and fistula
 Treatment: topical anesthetics, analgesics, antacid therapy,
dietary modification, anti-infectives
 Prevention
• MASCC: The panel suggests the use of amifostine to reduce
esophagitis induced by concomitant chemotherapy and
radiotherapy in patients with non-small cell lung cancer
• ASCO: insufficient data
Keefe DM, et al. Cancer 2007 Mar 1;109(5):820-31; Hensley et al. J. Clin Oncol, Vol 27, No 1 (January 1), 2009: pp.
127-145; Bradley J, Movsas B. Radiation Pneumonitis and Esophagitis in Thoracic Irradiation. In: Radiation Therapy-A
Practical Guide. 2006:43-64
Summary of Guideline
Recommendations: Prevention and
Treatment of Gastrointestinal Toxicity
Proctitis

Acute
• Occurs within ~ 6 weeks
• Diarrhea, rectal urgency,

bleeding
– Patients undergoing standard
RT for rectal cancer
RT complete
Chronic
• Onset 9 to 14 months
• Diarrhea, obstructed defecation,
bleeding, rectal pain or urgency,
fecal incontinence

 Amifostine
• Usually resolves on own once

Prevention
• Techniques of RT delivery
• MASCC Guidelines
 Sulfasalazine
– Patients receiving RT to pelvis

Treatment
• Surgery
• Fistulas, small bowel
obstruction, cystitis, urethral
stenosis
• Secondary malignancy
Babb, RR. Am J Gastroenterol 1996; 91:1309; 3. Haddock et al. J Clin Oncol 2007; 25:1255.; Keefe DM, et al.
Cancer 2007 Mar 1;109(5):820-31.

Prevention
• Recommended
 Sulfasalazine 500 mg orally twice daily to help reduce the
incidence and severity of radiation-induced enteropathy in
patients receiving external beam RT to the pelvis
 Amifostine in a dose >340 mg/m2 may prevent radiation proctitis
in patients who are receiving standard-dose RT for rectal cancer
• Not recommended
 Oral sucralfate should not be used to reduce related side effects
of RT
 5-amino salicylic acid and its related compounds mesalazine
and olsalazine not be used to prevent GI mucositis
Treatment
• Suggests the use of sucralfate enemas to help manage chronic
radiation-induced proctitis in patients who have rectal bleeding
Keefe DM, et al. Cancer 2007 Mar 1;109(5):820-31.
11
Radiation Oncology: Principles of
Therapy and Treatment-Related
Toxicity
HOPA 2010
Pneumonitis

Radiation Specific Factors
• Method of irradiation
• Volume of lung irradiated
• Dosage of radiation
• Time-dose factor
• Concurrent chemotherapy

Patient Factors
• Prior thoracic irradiation
• Volume loss due to lung
collapse
• Younger age
• Smoking history
• Poor pretreatment performance
status
• Poor pretreatment lung function
• Chronic obstructive pulmonary
disease
• Female sex
• Endocrine therapy for breast
cancer
Pneumonitis
 Symptoms
• Early nonproductive cough
• Dyspnea may only occur with exertion, or may be described
as an inability to take a deep breath
• Fever is usually low grade
• Chest pain may be pleuritic or substernal and can represent
pleuritis, esophageal pathology, or rib fracture
• Malaise and weight loss may be observed
 Treatment
• Steroids
• Pentoxifylline, amifostine, captopril
• Glucocorticoid withdrawal during
radiotherapy
Bradley J, Movsas B. Radiation Pneumonitis and Esophagitis in Thoracic Irradiation. In: Radiation Therapy-A Practical Guide.
2006:43-64
Stem Cell Transplantation:
TBI Side Effects
 Acute
•
•
•
•
 Late
Nausea
Mucositis
Parotiditis
Fatigue
• Cataracts
• Hypothyroidism
• Interstitial
pneumonitis
• VOD of liver
• Sterility
• Secondary
malignancy
TBI=total body irradiation; VOD=veno-occlusive disease
Palifermin: Results
 Significant reduction in grade 3-4
mucositis from 98% in the control
group to 63% in the KGF-treated
group
 Reduction of the median duration of
mucositis from 9 days (range: 1-22) in
the placebo group to 6 days (range: 127) in the KGF-treated group
 A reduction in the use of opioid
analgesics and TPN in KGF-treated
patients was also noted
 There were no differences in eventfree or overall survival
Spielberger R et al. N Engl J Med 2004 Dec 16;351(25):2590-8. TPN=Total Parenteral Nutrition
Mucositis with TBI plus Chemo:
Palifermin
 Evaluated in double-blind study of 212 patients
receiving auto HSCT
• Palifermin vs placebo on the development of oral
mucositis
• 106 patients received palifermin (60 mcg/kg/day)
and 106 received a placebo intravenously for 3
consecutive days immediately before the initiation
of conditioning therapy
• Conditioning regimen: fractionated total-body
irradiation plus high-dose chemotherapy
(etoposide and cyclophosphamide)
Spielberger R et al. N Engl J Med 2004 Dec 16;351(25):2590-8.
ASCO and MASCC Guidelines:
Palifermin
 Autologous stem-cell transplant
• Palifermin is recommended for use in patients
undergoing autologous SCT for a hematologic
malignancy with a TBI conditioning regimen
 Suggest the use of cryotherapy to prevent oral mucositis
in patients receiving high-dose melphalan (MASCC)
 Does not recommend the use of pentoxifylline or
granulocyte macrophage colony-stimulating factor (GMCSF) mouthwashes to prevent mucositis in patients
undergoing HSCT (MASCC)
Keefe DM, et al. Cancer 2007 Mar 1;109(5):820-31; Hensley et al. J. Clin Oncol, Vol 27, No 1 (January 1), 2009: pp.
127-145
12
Radiation Oncology: Principles of
Therapy and Treatment-Related
Toxicity
HOPA 2010
ASCO and MASCC Guidelines:
Palifermin
 Allogeneic stem-cell transplant
• Palifermin may be considered for use in patients
undergoing myeloablative allogeneic HSCT with a
TBI–based conditioning regimen
 Suggests the use of low-level laser therapy
(LLLT) to reduce the incidence of oral mucositis
and its associated pain in patients receiving highdose chemotherapy or chemoradiotherapy before
SCT (MASCC)
ASCO and MASCC Guidelines:
Palifermin
 Dose and administration of palifermin
• 60 mcg/kg intravenously daily for 3 days preceding
the start of the conditioning regimen and 60
mcg/kg intravenously daily for 3 days beginning on
the day of stem-cell infusion
• It should not be administered within 24 hours of the
initiation of the conditioning regimen
 Non–stem-cell transplantation and solid tumors
• There are insufficient data to recommend the use
of palifermin in the non–stem-cell transplantation
setting or for use in the treatment of solid tumors
Keefe DM, et al. Cancer 2007 Mar 1;109(5):820-31; Hensley et al. J. Clin Oncol, Vol 27, No 1 (January 1), 2009: pp.
127-145
Keefe DM, et al. Cancer 2007 Mar 1;109(5):820-31; Hensley et al, J Clin Oncol, Vol 27, No 1(January 1), 2009: pp.127-145.
Summary
Self-Assessment Questions
 Numerous acute and late side effects from
radiation therapy
 Advances in radiation therapy techniques
have altered the degree of toxicity severity
in some tumor types
 Evidence-based guidelines exist for some
side effects
1. The most common type of radiation used
is:
Self-Assessment Questions
Self-Assessment Questions
2. The potential benefits of fractionation
include:
A.
B.
C.
D.
E.
Decreases in injury to normal tissues
Allows total higher doses
Increases cell kill
B and C
All of the above
A.
B.
C.
D.
Photons
Electrons
Protons
Neutrons
3. Amifostine is recommended for the:
A. Prevention of xerostomia in patients receiving
radiation therapy for head and neck cancer
B. Prevention of xerostomia in patients receiving
platinum-based chemoradiotherapy for head and
neck cancer
C. Prevention of mucositis in patients receiving
radiation therapy for head and neck cancer
D. A and B only
E. All of the above
13
Radiation Oncology: Principles of
Therapy and Treatment-Related
Toxicity
HOPA 2010
Self-Assessment Questions
4.
Palifermin is recommended to decrease the incidence of
severe mucositis in which of the following clinical
scenarios:
A.
B.
C.
D.
Patients receiving TBI plus high-dose chemotherapy as a
conditioning regimen for an auto HSCT
Patients receiving high-dose chemotherapy as a
conditioning regimen for an auto HSCT
Patients receiving TBI plus high-dose chemotherapy as a
conditioning regimen for an allo HSCT
Patients receiving radiation therapy for head and neck
cancer
14