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Jonathan Sussman

Jonathan Sussman. Radiation Therapy for CTCL-Then and Now. Overview. Radiation Therapy Radiation in CTCL Radiation in the 70’s-90’s Radiation today Assumptions: background, staging and overall treatment sequencing have been discussed. Radiation Therapy a 30 second Physics course.

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Jonathan Sussman

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  1. Jonathan Sussman Radiation Therapy for CTCL-Then and Now

  2. Overview • Radiation Therapy • Radiation in CTCL • Radiation in the 70’s-90’s • Radiation today • Assumptions: background, staging and overall treatment sequencing have been discussed

  3. Radiation Therapya 30 second Physics course • Radiation =Energy travelling through space • Generated by a machine or from a radioactive source • Waves or Particles • Biological effect on tissue at the level of DNA • Rapidly dividing cells are the most sensitive • Can control how deep it penetrates by adjusting the energy

  4. How Radiation Works

  5. Radiation and CTCL a 2 minute HISTORY • 1895 Discovery of x-rays by Wilhelm Conrad Roentgen • 1899 First reported patient cured by radiation therapy • The skin is the 2nd most common extranodal site of lymphoma after the gastrointestinal tract • Jean Louis Marc Alibert coined the term Mycosis Fungoides in 1806. By 1870 it was recognized as a progressive cutaneous lymphoid disorder.

  6. Cell survivals with Radiation

  7. HISTORY • Radiation was used as early as 1902 to treat • CTCL • Total Skin Electron Beam (TSEB) technique was • developed by Stanford University in 1958 • By the end of the 1970’s, Hamilton Regional • Cancer Centre was the only Centre in Ontario • offering TSEB • Hamilton has treated nearly 1000 pts with TSEB • 2006 dedicated dermatologist retired, Hamilton joined • with Princess Margaret Hospital, Odette Cancer Centre • and Women’s College Hospital to form Provincial CTCL • group

  8. TELETHERAPY 1900 - 1920 • 1896 - First Roentgen ray tubes deliver energy 40 – 70 KV • 1913 - 140 KV • Introduction of radium teletherapy in 1915

  9. RADIATION THERAPY 1990 AND BEYOND

  10. AIM OF RADIATION THERAPY • To deliver a precisely measured dose of radiation to a defined tumour volume with minimal damage to the surrounding normal tissues. • ? How to do that when the “target” is the entire skin surface? • CT scans/MRIs and precision radiation techniques do not help

  11. Kim et al. 2005. J. Clin. Invest. 115: 793-812.

  12. The other form of energy-UV Light

  13. Electron Beams

  14. TOTAL SKIN ELECTRON BEAM • Need to cover the entire skin surface – patients must be naked for treatment. • 3 positions front and back designed to expose all skin areas – need to assess skin folds.

  15. TOTAL SKIN ELECTRON BEAM

  16. TOTAL SKIN ELECTRON BEAM

  17. TOTAL SKIN ELECTRON BEAM

  18. Radiation • Response in field generally upwards of 90% • Responses measured by fading of rash and more importantly reduction in symptoms • Duration of response for local therapy is dependant on biology and whether other therapies given ( re seeding) • TSEB as primary modality has response rates upwards of 75% and duration of response in early stage measured in years, in later stages generally months • Hard to determine accurately as rarely given as solo modality of treatment

  19. SIDE EFFECTS • Predominately skin – includes both the general skin and the structures of the skin – hair follicles, nails and sweat glands. • Tend to start the third or fourth week of treatment. • Skin may become erythematous, scaly/flaky and pruritus may occur. Open areas may occur especially in skin folds, hands and feet – potential for skin infection. • Hair loss begins in 3rd week. Can lose all or part of body hair. Generally grows back 2 –4 months post treatment. May come back a different colour or texture. • Fingernails and toenails stop growing because of TSEB. Nail loss is possible. Growth is suspended for 2 – 6 weeks. As new nails grow, old nails become a bit thicker and may feel loose.

  20. Radiation Dermatitis

  21. Late effects:skin atrophy and telangiectasia

  22. 1970’s-1990’s • Refinement of TSEB technique • Optimal Dose defined • Most could tolerate 4-6 week course with shielding and breaks • Few therapies other than radiation • Chemo for other hematological malignancies had transient benefit with lots of toxicity • Effective skin clearing for most patients • Single institution experiences

  23. BUT...... • Lots of long term toxicity from radiation • Few comparative studies • Most patients recurred with longer follow up • Early clearance did not appear to prevent later stages –biological destiny • Localized treatment in early stages or to ‘de bulk” thick plaques or tumours had equal long term outcomes • Results from studies of “Add on” treatment inconsistent in supporting longer responses • Chemo or IFN after radiation

  24. 2000’s • Development of new biological agents to tackle the root cause of CTCL • Observation that low doses of radiation for local areas as effective as higher doses • EORTC GUIDELINES 2004 • RT is a skin directed therapy • “save it til you need it approach” • Body can only take so much radiation, used in sequence with other therapies quality of skin/life overall better • Better able to target radiation

  25. Mycosis Fungoides Treatment Ladder: • Stage-based. • Skin-directed therapy usually starting point and component of all therapies. • Stage 1A/B and 2A: • Topical Corticosteroids. • Topical Retinoids. • Topical imiquimod. • Light therapy (UVB; PUVA). • Total skin electron beam (TSEB). • Light + systemic • (oral retinoid + PUVA) • (Interferon + PUVA)

  26. Mycosis Fungoides Treatment Ladder: • Stage 2B and higher: • Phototherapy and TSEB as adjuncts. • Local electron beam to tumours. • Oral retinoids. • Interferon. • Histonedeacetylase inhibitors. • Methotrexate. • Extracorporealphotophoresis (if circulating clone). • Pruritus is a significant component of this disease: • Menthol, camphor. • Sedating antihistamines. • Gabapentin, mirtazapine.

  27. Our Approach today • Early stage spot radiation • 5-20 treatments • Spot radiation early on for bulky or symptomatic sites • 1-5 treatments • Save TSEB for progression if other therapies stop working • Lower dose/less cumbersome positioning for older patients who have trouble with usual TSEB technique

  28. Today • 15-20 people treated per year with TSEBT • 20+ treated with spot radiation • Short term control rates in excess of 80% • Average duration of response 18 months • 20% may have long term ( years) remission • Mostly early stage disease

  29. THANK YOU • Debra Gallinger • PERC • Odette Hematology • UHN ECP unit • Patients

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