Radiotherapy-Induced Dermatologic Toxicities

1. Radiotherapy-Induced Dermatologic Toxicities Jennifer Nam Choi, MD Yale University School of Medicine Department of Dermatology Yale Cancer Center New Haven, CT

2. Disclosure of Relevant Relationships with Industry Jennifer N. Choi, MD Radiotherapy-Induced Dermatologic Toxicities I do not have any relevant relationships with industry.

3. Radiotherapy Reactions and Complications From Bolognia, Jorizzo & Rapini. Dermatology 2e. 2008 Elsevier, Ltd.

4. Radiotherapy Reactions and Complications From Bolognia, Jorizzo & Rapini. Dermatology 2e. 2008 Elsevier, Ltd.

5. Radiotherapy Reactions and Complications Radiation Dermatitis From Bolognia, Jorizzo & Rapini. Dermatology 2e. 2008 Elsevier, Ltd.

6. Locations Most Associated with Radiation Dermatitis • Head/Neck • Chest wall • Breast • Lung • Genitourinary • Uterine • Cervical

7. Grading System of Radiation Dermatitis • National Cancer Institute (NCI) • Radiation Therapy Oncology Group (RTOG) • World Health Organization (WHO) • European Organization for Research and Treatment of Cancer (EORTC)

8. Grading System of Radiation Dermatitis • National Cancer Institute (NCI) • Radiation Therapy Oncology Group (RTOG) • World Health Organization (WHO) • European Organization for Research and Treatment of Cancer (EORTC)

9. Acute: Radiation Dermatitis • Erythema • Xerosis

10. Acute: Radiation Dermatitis • Erythema • Xerosis • Hyperpigmentation • Dry desquamation • Pruritus • Moist desquamation • Pain • 2-4 weeks, 20-25 Gy • 80-90%

11. Acute: Radiation Dermatitis • Erythema • Xerosis • Hyperpigmentation • Dry desquamation • Pruritus • Moist desquamation • Pain • 2-4 weeks, 20-25 Gy • 80-90% • Severe reactions: • Total radiation dose • Dose per fraction • Overall treatment time • Beam type and energy • Surface area of skin exposed • Chemotherapy

12. Breast Irradiation • Radiation Beam • Radiation Beam • Breast • Ribs • Heart • Lungs • Vertebrae • Sternum (breast bone)

14. Breast Irradiation • BOOST AREA: location of extra radiation to the lumpectomy site after the initial course of radiation • May outline area to direct the radiation beams using: • Tattoos • Adhesive tape • Remains on skin for entire duration of treatment e.g. 4 to 8 weeks • Not permanent

15. Radiation Dermatitis Management • Controversial

16. Study Descriptions and Trial Outcomes on Preventing Acute Radiation Skin Reactions 1 Bostrom A et al, Radiother Oncol 2001; 2 Schmuth M et al, Br J Dermatol 2002; 3 Løkkevik E et al, Acta Oncol 1996; 4 Roy I et al, Radiother Oncol 2001; 5 Campbell IR et al, Clin Oncol 1992; 6 Westbury C et al, Radiother Oncol 2000; 7 Lievens Y et al, Radiother Oncol 1998; 8 Evensen JF et al, Acta Oncol 2001; 9 Maiche A et al, Acta Oncol 1994.

17. Study Descriptions and Trial Outcomes on Preventing Acute Radiation Skin Reactions 1 Fenig E et al, Oncol Rep 2001; 2 Fisher J et al, J RadiatOncolBiol Phys 2000; 3 Pommier P et al, J ClinOncol 2004; 4 Gujral MS et al, Cancer ChemotherPharmacol2001; 5 Dale PS et al, Cancer ChemotherPharmacol 2001; 6 Kaul R et al, Indian J Cancer 1999; 7 Dunst J et al, StrahlentherOnkol 2000.

18. Study Descriptions and Trial Outcomes on Preventing Acute Radiation Skin Reactions 1 Liguori V et al, RadiotherOncol1997; 2 Halperin EC et al, Int J RadiatOncolBiol Phys 1993; 3 Heggie S et al, Cancer Nurs2002; 4 Olsen DL et al, OncolNurs Forum 2001; 5 Williams MS et al, Int J RadiatOncolBiol Phys 1996; 6 Maiche AG et al, ActaOncol1991; 7 Hazuka MB et al, Proc Am Soc ClinOncol 1997.

19. Study Descriptions and Trial Outcomes on Preventing Acute Radiation Skin Reactions 1 Schreck U et al, StrahlentherOnkol2002; 2 Potera ME et al, RadiotherOncol1982; 3 Delaney G et al, AustralasRadiol1997; 4 Shell JA et al, OncolNurs Forum 1986; 5 Mak SS et al, Cancer Nurs2000.

20. Supportive Care Guidelines Group (Ontario) Prevention of acute skin reaction • Gentle washing with water alone or with mild soap and water • Insufficient evidence to support or refute specific topical agents • Corticosteroids, sucralfate cream, Biafine, ascorbic acid, aloe vera, chamomile cream, almond cream polymer adhesive skin sealant • Insufficient evidence to support or refute specific oral or IV agents • Enzymes, sucralfate • Amifostine Management of acute skin reaction • Insufficient evidence to support or refute specific topical agents • Corticosteroids, sucralfate cream, specific dressings Bolderston et al. The prevention and management of acute skin reactions related to radiation therapy: a systematic review and practice guideline. Support Care Center (2006) 14:802-817.

21. Supportive Care Guidelines Group (Ontario) • Plain, non-scented, lanolin-free hydrophilic cream • Discontinue if skin breakdown occurs • Low dose corticosteroid cream may be beneficial in reducing itching and irritation • Caution in overusing corticosteroid cream • But limited evidence to suggest that average course of treatment (i.e. 8 weeks) would produce skin thinning Bolderston et al. The prevention and management of acute skin reactions related to radiation therapy: a systematic review and practice guideline. Support Care Center (2006) 14:802-817.

22. Radiotherapy Reactions and Complications From Bolognia, Jorizzo & Rapini. Dermatology 2e. 2008 Elsevier, Ltd.

23. Radiotherapy Reactions and Complications From Bolognia, Jorizzo & Rapini. Dermatology 2e. 2008 Elsevier, Ltd.

24. Subdermal fibrosis

25. Subdermal fibrosis

26. Postirradiation Morphea 9 months 1 year 3.5 years Cheah et al. J Medical Case Reports. (2008) 2:136

29. Reports of Postirradiation Morphea 1 Cooper SG, Denham JW, Br J Radiol 1990; 2 Abu-Shakra M et al, Arthritis Rheum 1993; 3 Schaffer JV et al, Dermatology 2000; 4 Ullén H et al, Int J Gynecol Cancer 2003; 5 Reddy SM et al, Semin Arthritis Rheum 2005; 6 Dubner S et al, Breast J 2006; 7 Ardern-Jones M, Black MM, Clin Exp Dermatol 2003; 8 Seale M et al, Breast J 2008; 9 Walsh N et al, Hum Pathol 2008; 10 Herrmann T et al, Strahlenther Onkol 2009.

31. Treatment: Post Irradiation Morphea • CASE STUDY TREATMENT: • Topical clobetasol • Potent topical steroid • Treatment option for post irradiation morphea • Addressed quickly, so condition improved • MORE SEVERE CASES: • Oral corticosteroids • Helps with condition • Emphasizes importance of distinguishing post irradiation morphea and dermal fibrosis

32. Possible Mechanism of Action for Development of Post Irradiation Morphea Schaffer et al. Dermatology. (2000) 200:67-71

33. Adverse reactions of radiation • Considerable inter-individual variability • Duration • Radiation dose • Schedule • Age • Acute skin reaction • Lifestyle factors • Genetic susceptibility

34. Radiation Recall Dermatitis (RRD) • “Recalling” by skin of previous radiation exposure, usually subsequent to cytotoxic drugs or antibiotics • Median: 39 days • 7 days - 15 years • <2 month separation between radiation therapy and drug administration • Tumor doses 10 - 61.2 Gy

35. Radiation Recall Dermatitis (RRD) • “Recalling” by skin of previous radiation exposure, usually subsequent to cytotoxic drugs or antibiotics • Median: 39 days • 7 days - 15 years • <2 month separation between radiation therapy and drug administration • Tumor doses 10 - 61.2 Gy • Mechanism unknown • Vascularization, DNA repair, radiation-impaired epithelial function of stem cells, increased sensitivity to drugs

36. Radiation recall dermatitis-inducing drugs (n = 75) Current Oncol. 15(1):53-62, 2008

37. Additional RRD Culprits • Trastuzumab • Sunitinib • Sorafenib • Erlotinib • Cetuximab

38. Summary Acute Chronic • Management of Radiation Dermatitis • Washing, moisturization and low-strength topical steroids • Further research • Postirradiation Morphea vs. Subdermal Fibrosis • Radiation Recall Dermatitis