Radiation Therapy for CTCL-Then and Now

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 =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

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.

• 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

1896 - First Roentgen ray tubes deliver energy 40 – 70 KV

1913 - 140 KV Introduction of

radium teletherapy in 1915

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

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

•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.

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

•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.

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

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

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

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)

Stage 2B and higher: Phototherapy and TSEB as adjuncts. Local electron beam to tumours. Oral retinoids. Interferon. Histone deacetylase inhibitors. Methotrexate. Extracorporeal photophoresis (if circulating clone).

Pruritus is a significant component of this disease: Menthol, camphor. Sedating antihistamines. Gabapentin, mirtazapine.

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

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

Debra Gallinger PERC Odette Hematology UHN ECP unit Patients