Misc Normal

Bone Marrow

• Circulating lymphocytes are directly killed by low dose radiation (TBI)

Breast

• Preadolescent breast development is inhibited in 5% of the population at 10 Gy and 50% at 15 Gy.

CNS

• Oliogodendrocytes are responsible for myelination
• For pediatric patients with localized ependymoma, a limited volume of the upper cervical spinal cord may receive 54 Gy over the course of 6 weeks with minimal risk of spinal cord injury. Additional dose to the spinal cord beyond 54 Gy does not contribute additional risk, phttp://www.wikidot.com/doc:wiki-syntaxrovided the daily fraction size is limited to 1.25 Gy. (T. E. Merchant. A Prospective Study of Spinal Cord Dosimetry and Neurologic Outcome for Infratentorial Ependymoma. IJROBP 1 November 2006 (Vol. 66, Issue 3, Page S111))

Cauda equina

• No patients devleoped neural injury at ≤ 70.2 Gy RBE. Suspect nerve injury to occur between 70.2 to 77.4 Gy^[13]

Brachial Plexus

• .4% complication with ≤ 50 Gy without chemotherapy and 3.4% with chemotherapy
• 60 Gy can be delivered with complications in <5% of patients. ( Choa KS, Perez C, Brady L. Radiation Oncology: Management Decisions. Philadelphia, PA: Lippincott-Raven Publishers, 1999. )

Treatment

• trandermal electrical nerve stimulation
• dosal column stimulators
• neurolysis
• neurolysis with omentoplasty
• physical therapy
• tricyclics
• antiarrhythmics
• anticonvulsives
• NSAID and Steroids

SBRT

• The 2-year risk of brachial plexopathy was 46% after the brachial plexus received a biologically effective dose maximum (BED) of >100 Gy
• 8% for BED <100 Gy [6].
• Anther study reported brachial plexopathy in 1 of 60 patients due to significant volume of brachial plexus receiving 40 Gy in 4 fractions. [7]

EAR (COCHLEAR)

• a significant hearing loss was noted after a cochlear dose of ≥ 60 Gy in 60% of the patients and no patient after a dose of < 60 Gy when treating the parotid in adults. (Chen et al Ann Otol Rhinol Laryngol 1999; 108: 1159-1164).
• a dose of ≤ 30 Gy should be attempted.

Eye

Lens of eye(Cataract)

• Min. dose = 2Gy
• RBE of neutron or heavy iron is 20 but as high as 50
• Result of accumulation of dead cells
• 2-6.5 Gy Stationary cataract
• 6.5-11.5 Gy Progressive Cataract

Lung

General

• is an intermediate- to late-responding tissue with alpha/beta of 3. The lung is among the most sensitive of late-responding tissues.

Radiation Pneumonitis

• surfactant proteins, IL-6, and IL-1α] have been identified as early circulating cytokine markers for RP. Anscher et al. (IJROBP 1998)[28] have extensively evaluated in clinical studies the role of plasma transforming growth factor-β1 (TGF-β1) in the development of RP.
• (Katrien De Jaeger M.D., M.Sc. Significance of plasma transforming growth factor-β levels in radiotherapy for non–small-cell lung cancer IJROBP 1 April 2004, Pages 1378-1387)

== DVH for Lung and Surrounding Tissues for Lung Irradiation ==

Radiation Bronchitis

This disease entity was originally described by Speiseret al.[12] The concept of the hyperdose sleeve may reasonably explain the high dose volume produced by intraluminal brachytherapy sources.[11] As for the proximal airway, several series have reported tracheal stenosis after external beam radiation therapy using up to 70 Gy.[8],[9] Hayakawa et al. reported the deleterious effect of 80 Gy in 40 fractions to the proximal bronchi.[10]

GI

Liver

• no upper limit if < 25% of the normal liver is treated
• 5% risk for uniform irradiation of

1/3	90 Gy
2/3	47 Gy
whole liver	31 Gy

(Dawson et al. Sem Rad Onc 01).

OVARY

Radiation Effect On Fertility: Ovary^[5]
• Under 2Gy radiation can destroy 50% of
the immature oocytes
• 20-30 Gy total abdominal therapy
– 97% post-pubertal women experience premature ovarian failure
– 72% pre-pubertal girls lose ovarian function
• Degree of ovarian dysfunction is related to
– Dose
– Fractionation schedule
– Age and time of therapy
– Gonadal shielding

Skin

• Low dose hypersensitivity can occur at 0.5 Gy per fraction*
• At 2 Gy maximum resistance to radiation occurs and skin erythema is rarely seen from 2-7 Gy

Small Bowel Tolerance

Testes

• Transit time from stem cell to spermatozoa is 74 days.
• 0.1 Gy leads to tremporary reduction in # of spermatozoa
• 0.15 Gy leads to temp. sterility
• 2 Gy leads to Azoospermia x 2 years

• 6-8 Gy permanent Azoospermia.
• 1 Gy TD 5/5 for Sterility
• 20 Gy TD 5/5 for Leydig cells (testosterone)
• B-spermatogonia are killed
• Fractionation decreases the tolerance for sterility due to reassortment

TESTIS

Radiation Effect On Fertility: Testis^[3],[4]
• Dose dependent effect on sperm parameters
– Greater than 4-6 Gy: permanent azoospermia
– Greater than 1.2 Gy: azoospermia
– Lower doses show varying degrees and durations of sperm impairment
– Direct testicular irradiation has an 8.2-fold increase risk of azoospermia

Vaginal Surface Dose tolerance in thirds^[1]

• Proximal 150 Gy
• "The traditional 150 Gy LDR tolerance dose (single source plus external irradiation) can be relaxed to 175 Gy or equivalently a full mucosal dose of 238 Gy (all sources plus external irradiation) for a nominal 5% Grade 3 complication rate."^[2]
• Middle 90 Gy
• Distal 90 cGy
• Whole vaginal < 80 Gy

Treatment of Fibrosis

Pentoxifylline

• and inhibitors of TGF-beta can reduce fibrosis even afer its clinical development.

TGF-beta

• Potent growth inhibitor and inducer of apoptosis, suppresses anti-tumor immune responses. binds to type I and type II receptors leading to signaling of SMAD family of intracellular mediators.

Bibliography

1. Hintz BL, Kagan AR, Chan P, Gilbert HA, Nussbaum H, Rao AR, Wollin M.Radiation tolerance of the vaginal mucosa. Int J Radiat Oncol Biol Phys. 1980 Jun;6(6):711-6. No abstract available. PMID: 7451275

2. Au SP, Grigsby PW. The irradiation tolerance dose of the proximal vagina. Radiother Oncol. 2003 Apr;67(1):77-85. PMID: 12758243

3. Bahadur G, Mol Cell Endocrinol 2000;169:117-122

4. Thomson et al., Europ J Cancer 2002;38:1634-44)

5. Critchley and Wallace, J Natl Cancer Inst Monogr 2005;34:64–8

6. Forquer JA, Fakiris AJ, Timmerman RD, Lo SS, Perkins SM, McGarry RC, Johnstone PAS: Brachial plexopathy (BP) from stereotactic body radiotherapy (SBRT) in early-stage NSCLC: Dose-limiting toxicity in apical tumor sites [abstract]. Int J Radiat Oncol Biol Phys 2008, 72:S36-37

7. Chang JY, Balter P, Dong L, Bucci MK, Liao Z, Jeter MD, McAleer MF, Yang Q, Cox JD, Komaki R: Early results of stereotactic body radiation therapy (SBRT) in centrally/superiorly located stage I or isolated recurrent NSCLC [abstract]. Int J Radiat Oncol Biol Phys 2008, 72:S463.

8. Rostom AY, Morgan RL. Results of treating primary tumours of the trachea by irradiation. Thorax, 33: 387–393, 1978.

9. Mornex F, Coquard R, Danhier S, Maingon P, El Husseini G, Van Houtte P. Role of radiation therapy in the treatment of primary tracheal carcinoma. Int J Radiat Oncol Biol Phys, 41: 299–305, 1998.

10. Hayakawa K, Mitsuhashi N, Saito Y, Nakajima N, Niibe H. Adverse chronic effects of high-dose irradiation onproximal bronchus in patients treated for bronchogeniccarcinoma. Br J Radiol, 66: 477–479, 1993.

11. Marinello G, Pierquin B, Grimard L, Barret C. Dosimetry of intraluminal brachytherapy. Radiother Oncol, 23: 213–216, 1992.

12. Speiser BL, Spratling L. Radiation bronchitis and stenosis secondary to high dose rate endobronchial irradiation. Int J Radiat Oncol Biol Phys, 25: 589–597, 1993.

13. DeLaney et al. Phase II Study of High-dose Photon/proton radiotherapy in the managmenet of spine sarcomas. IJROBP 2009, 74: 732-39.