Transcript Radiation Therapy for CTCL-Then and Now

Radiation Therapy for CTCLThen and Now
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Radiation Therapy
Radiation in CTCL
Radiation in the 70’s-90’s
Radiation today
Assumptions: background, staging and overall
treatment sequencing have been discussed
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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
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1895 Discovery of x-rays by Wilhelm Conrad
Roentgen
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1899 First reported patient cured by radiation
therapy
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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
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1896 - First
Roentgen ray tubes
deliver energy 40 –
70 KV
1913 - 140 KV
Introduction of
radium
teletherapy in 1915
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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?
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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.
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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
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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.
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Refinement of TSEB technique
Optimal Dose defined
Most could tolerate 4-6 week course with
shielding and breaks
Few therapies other than radiation
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Chemo for other hematological malignancies had
transient benefit with lots of toxicity
Effective skin clearing for most patients
Single institution experiences
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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
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Chemo or IFN after radiation
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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”
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Body can only take so much radiation, used in
sequence with other therapies quality of skin/life
overall better
Better able to target radiation
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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)
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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.
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Early stage spot radiation
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Spot radiation early on for bulky or
symptomatic sites
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5-20 treatments
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
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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
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Mostly early stage disease
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Debra Gallinger
PERC
Odette Hematology
UHN ECP unit
Patients