CANCER RISKS AFTER

RADIOTHERAPY FOR BENIGN

CONDITIONS
HAZEM EL-GAMAL, MD
RICHARD BENNETT, MD
MOHS MICROGRAPHIC
SURGERY &
DERMATOLOGIC SURGERY
SANTA MONICA PASADENA UCLA USC DREW/KING
WILHELM CONRAD RNTGEN
(ROENTGEN)
GERMAN PHYSICIST
(1845-1923)
PHYSICS INSTITUTE
(WURZBURG, GERMANY)
DISCOVERED X-RAYS
IN NOVEMBER 1895
WINNER NOBEL PRIZE
PHYSICS 1901
HISTORY OF X-RAYS
1859 Plueber (Germany)-Vacuum Tube
Fluoresced
1860 Hittorf (Germany)-Luminous Stream
Detected by Magnet
1875 Wm. Crookes(English)-High Vacuum
Tube; Cathode Ray - Apple Green
Light
1893 Herbert J ackson (English)-Anode to
Catch Cathode Stream
HISTORY OF X-RAYS (Cont.)
1893 H. Hertz (Germany) - Cathode Rays
Through ??
1893 R. Leonard (Germany) - Showed
Substances Fluoresced With Cathode Rays
1895 Roentgen (Germany) - Darkened Room,
Put Hand between Chemical & Tube
EARLY X-RAY
IMAGE
(Frau Roentgens
Hand) c. 1895
FORMATION OF THE CATHODE STREAM
AND X-RAYS
X-RAY TUBE EASILY
OBTAINED
1898 BRITISH ADVERTISEMENT

EARLY X-RAY MACHINE

RADIOSENSITIVITY
Frances Williams, MD
The Roentgen Rays in Medicine & Surgery
MacMillan, Co; New York 1901
Fat
Muscle
Bone
THOMAS A. EDISON
1896 Fluoroscopic Exhibit
National Electric Light Association, NYC
SIDE EFFECTS OF X-RAY
DERMATITIS (1896)
SUNBURN
WARTS (1898)
SQUAMOUS CELL
CARCINOMA
METASTASIS (1907)
INTERNAL CANCER
(1950)
ELECTROMAGNETIC SPECTRUM
PERCY BROWN, MD
AMERICAN MARTYRS TO SCIENCE THROUGH
ROENTGEN RAYS
CHARLES C. THOMAS, SPRINGFIELD, 1936
REPORTS 26 WORKERS IN X-RAY WHO
DIED OF SCC, MOSTLY ON LEFT HAND
THAT METASTASIZED
16 MDS (7/16 IN LATE 30 OR 40 YRS OF AGE)
EARLY FLUOROSCOPE USING
HAND TO FOCUS
EARLY FLUOROSCOPE USING
FOREARM BONES TO FOCUS
SCC AFTER RADIOTHERAPY
FOR ECZEMA
X-RAYS IN DERMATOLOGY
1898 FIRST REPORTED TO BE USEFUL
IN ACNE
1899 SCHIFF & FRIEND, HAIR IN
NEVUS
1902 DR. PUSEY PUBLISHES
TEXTBOOK
1907 DR. MACKEE PUBLISHES
TEXTBOOK
William A. Pusey,
MD (1865-1940)
Professor Dermatology
U. of Illinois Medical School
Introduced Radiotherapy to
Dermatology
EARLY X-RAY TECHNIQUE
Wm. A. Pusey
Early Textbook by
Dermatologist
Featuring Radiology,
1907
George M. MacKee,
MD (1878-1955)
PROFESSOR
DERMATOLOGY
NEW YORK SKIN &
CANCER
MacKees Standard
Textbook
Radiotherapy in
Dermatology
4 Editions
(1921, 1927, 1938, 1946)
Rose Hirschler,
MD (1875-1940)
Professor Dermatology
Womens Medical
School, Phil.
Began Radiotherapy
Dept.
Died of Leukemia
SKIN PENETRATION BY X-RAYS
1903 BCC INNER CANTHUS
Treated with X-ray
Rodent
Ulcer
STUDY OVERVIEW
17,382 CHARTS REVIEWED FROM 1978-2003
CASE GROUP
432 PATIENTS FOUND THAT RECEIVED
RADIOTHERAPY FOR BENIGN CONDITIONS
CONTROL GROUP
RANDOMLY SELECTED
AGE AND GENDER MATCHED 1:1 TO CASES
INDICATIONS FOR
RADIOTHERAPY
Dermatologic Number/(%)
Acne 357/(82.8)
Eczema 17/(3.9)
TineaCapitis 9/(2.1)
Psoriasis 4/(0.9)
Dermatitis/NOS 4/(0.9)
SeborrheicDermatitis 3/(0.7)
Hair Loss 2/(0.5)
Neurodermatitis 2/(0.5)
INDICATIONS FOR
RADIOTHERAPY (Cont.)
Dermatologic (cont.) Number/(%)
Yeast 1/(0.2)
Hyperhidrosis 1/(0.2)
Oily Skin 1/(0.2)
Keloid 1/(0.2)
TineaPedis 1/(0.2)
Impetigo 1/(0.2)
Hemangioma 1/(0.2)
TineaFacei 1/(0.2)
INDICATIONS FOR
RADIOTHERAPY (Cont.)
Dermatologic (cont.) Number/(%)
Pruritis 1/(0.2)
Wart 1/(0.2)
Folliculitis 1/(0.2)
Erythema 1/(0.2)
Actinomycosis 1/(0.2)
INDICATIONS FOR
RADIOTHERAPY (Cont.)
ENT Number/(%)
Sinus Problems 6/(1.4)
Tonsils 2/(0.5)
Eustachian Tube 1/(0.2)
Asthma 1/(0.2)
Whooping Cough 1/(0.2)
INDICATIONS FOR
RADIOTHERAPY (Cont.)
Orthopaedic Number/(%)
Tendinitis 1/(0.2)
AnkylosingSpondylitis 1/(0.2)
GOLDSCHMIDT, H.
IONIZING RADIATION THERAPY IN
DERMATOLOGY
ARCH DERMATOL 111:1511-1517, 1975
SURVEY OF U.S. AND CANADIAN
DERMATOLOGISTS
2,305 RESPONSES TABULATED
89.3
41.8
34.6
23.9
0
10
20
30
40
50
60
70
80
90
Percent (%)
BCC Acne Eczema Psoriasis
Indications for Radiotherapy
DERMATOLOGISTS USING
SUPERFICIAL X-RAY THERAPY (1975)
CANCER AND IONIZING
RADIATION
Cancer
X-Rays
DATE INJURY REPORTED BY
1896 Dermatitis hands Grubbe
1896 Epilation Daniel
1902 CA in X-ray Ulcer Frieben
1911 Leukemia in 5 Radiation J agic
Workers
1912 Anemia in 2 X-ray Workers Belere
1949 BCC in 5 yr old Child Scharnajel/Pack
1950 Thyroid Cancer in X-ray for Thymus Duffy/Fitzgerald
SCHARNAGEL, IM, PACK, GT
MULTIPLE BASAL CELL EPITHELIOMAS IN
A 5 Y.O. CHILD
AM. J. DIS CHILD 77:647-651 (1949)
BCCS DEVELOP IN PORT AREA FOR
RADIATION TO THYMUS GLAND
DUFFY, BJ, JR., FITZGERALD, PJ
THYROID CANCER IN CHILDHOOD &
ADOLESCENCE
CANCER 1018-1032 (1950)
10/28 CASES HAD HAD X-RAY FOR
ENLARGED THYMUS GLAND IN
INFANCY
Marion Sulzberger,
MD (1895-1984)
PROFESSOR &
CHAIRMAN
Dept. of Dermatology
NYU School of Medicine
SULZBERGER, MB, BAER, RL, BOROTA, A
DO ROENTGEN-RAY TREATMENTS AS GIVEN
BY SPECIALISTS PRODUCE CANCERS OR
OTHER SEQUELAE?
ARCH DERM SYPH 65:639-655 (1952)
REEXAMINED 1000 PATIENTS
IRRADIATED AND 1000 NON-IRRADIATED
PATIENTS
NO SKIN CANCERS WITH 5-23 YEARS OF
FOLLOW-UP
BCCsAFTER RADIOTHERAPY
FOR ACNE
INCIDENCE ANGLES FOR X-RAY
TREATMENT OF ACNE AND TINEA BARBAE
(MacKee Textbook 1946)
NMSC
STUDY INFORMATION
432 PATIENTS IRRADIATED FOR BENIGN
MEDICAL CONDITIONS
148 MEN
284 WOMEN
MEAN AGE 65 YEARS FOR CASES &
CONTROLS
NMSC
Mean Number of NMSC in Cases & Controls
7.1
3.5
0.21 0.2
0
1
2
3
4
5
6
7
8
Number
Mean Number of
BCC (p <0.0001)
Mean Number of
SCC (p=0.22)
Cases
Controls
NMSC
Mean Age of First NMSC in Cases & Controls
53.9
60
50
51
52
53
54
55
56
57
58
59
60
Age (yrs)
Mean Age at First NMSC
(p-value <0.0001)
Cases
Controls
NMSC
Mean Number of NMSC in the Central Face
for Cases & Controls
1.63
1.2
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
Number of
NMSC
Mean Number of NMSC in
Central Face
(p-value = 0.0001)
Cases
Controls
NMSC
Location of Presenting NMSC in Cases &
Controls
81.5
77.3
9.7
12.8
8.8 9.9
0
10
20
30
40
50
60
70
80
90
Percent (%)
Mid-face Lateral
Face
Other
(non-significant)
Cases
Controls
THYROID DISEASE
Odds Ratio of Thyroid Cancer & Non-cancer
Thyroid Problems
17.62
2.34
0
2
4
6
8
10
12
14
16
18
Odds Ratio
(OR)
Thyroid Cancer
(p-value = 0.000125)
Non-cancer Problems
(p-value = 0.000075)
BREAST CANCER AND IONIZING
RADIATION
Breast
Cancer
Ionizing
Radiation
MCGREGOR, DH, ET AL
ATOMIC BOMB SURVIVORS - HIROSHIMA,
NAGASAKI
J. NATL. CANCER INST. 59:799-811 (1977)
RELATIVE RISK AGE AND DOSE
BUT AGE (10-19) >> DOSE
STUDY DOSE O/E
Atomic Bomb J apan 30 R 1.6
Postpartum Mastitis 380 R 4.5
Multiple Fluoroscopic Exams 70-100 R 0.9-1.7
Skin Hemangiomas 17-52 R 1.15-1.3
HodgkinsDisease
TineaCapitis
Enlarged Thymus 70 R 3.5
X-RAYS BREAST CANCER
BREAST CANCER
Study Information
244 WOMEN IRRADIATED FOR ACNE
244 AGE MATCHED WOMEN
CONTROLS
MEAN YEARS F/U: 49 YRS
MEAN AGE:
CASES: 66.2 YRS
CONTROLS: 65.8 YRS
BREAST CANCER
Study Information (cont.)
Number of Breast
Cancers
Cases: 36
Controls: 16
OR: 2.47
P-value: 0.0033
36
16
0
5
10
15
20
25
30
35
40
Number
Cases Controls
STANDARD RADIOTHERAPY
TECHNIQUE
(Goldschmidt 1994, J . Am. Acad. Derm. 30:173)
BREAST CANCER
Odds Ratio of Breast Cancer vs. Age at
XRT
2.47
2.72
1.75
0
0.5
1
1.5
2
2.5
3
Odds Ratio
(OR)
All Women
(p=0.0033)
Age <20
(p=0.0022)
Age>20
(p=0.26)
BREAST CANCER
Odds Ratio of Breast Cancer vs.
Number of Treatments
2.47
3.95
1.78
0
0.5
1
1.5
2
2.5
3
3.5
4
Odds Ratio
(OR)
All Women
(p=0.0033)
Number >=5
(p=0.0029)
Number <5
(p=0.36)
BREAST CANCER
Odds Ratio of Breast Cancer vs. Year
of Treatment
2.47
3.35
0.66
0
0.5
1
1.5
2
2.5
3
3.5
Odds Ratio
(OR)
All Women
(p=0.0033)
Year of XRT
<1950
(p=0.00014)
Year of XRT
>=1950
(p=0.77)
BREAST CANCER
Odds Ratio of Breast Cancer vs.
Anatomic Location of Radiotherapy
2.47
2.28
3.99
0
0.5
1
1.5
2
2.5
3
3.5
4
Odds Ratio
(OR)
All Women
(p=0.0033)
Face Only
(p=0.016)
Face + Other
Site (p=0.0093)
BREAST CANCER
Odds Ratio of Breast Cancer
Multivariate Analysis
2.47
3.34
1.89
0
0.5
1
1.5
2
2.5
3
3.5
Odds Ratio
(OR)
All Women
(p=0.0033)
Age <20 &
Year
XRT<1950
(p=0.0004)
Age >20 &
Year of XRT
>=1950
(p=0.42)
BREAST CANCER
Odds Ratio of Breast Cancer
Multivariate Analysis
2.47
4.1
0
0.5
1
1.5
2
2.5
3
3.5
4
4.5
Odds Ratio
(OR)
All Women
(p=0.0033)
Age <20 & Year
XRT<1950 &
Treatment Number >=5
(p=0.0066)
BREAST CANCER
Prevalence of Breast Biopsies in Non-
cancer Cases and Controls
6.28
2.19
0
1
2
3
4
5
6
7
Prevalence
(%)
Prevalence of Breast Biopsies in Non-
cancer Cases & Controls
(OR = 2.98, p-value = 0.0511)
Cases
Controls
CONCLUSIONS
NMSC
PATIENTS THAT RECEIVED RADIOTHERAPY
FOR BENIGN CONDITIONS:
NO INCREASED RISK OF DEVELOPING SCC
DEVELOP A GREATER NUMBER OF BCCS
DEVELOP NMSC AT EARLIER AGE
DEVELOP GREATER PROPORTION OF NMSC IN
THE CENTRAL FACE
CONCLUSIONS
THYROID CANCER
PATIENTS THAT RECEIVED RADIOTHERAPY
FOR BENIGN CONDITIONS:
INCREASED RISK (OR 17.6) FOR DEVELOPING
THYROID CANCER
INCREASED RISK (OR 2.34) FOR DEVELOPING NON-
CANCER THYROID PROBLEMS
CONCLUSIONS
BREAST CANCER
WOMEN THAT RECEIVED RADIOTHERAPY
FOR ACNE:
INCREASED RISK (OR 2.47) FOR DEVELOPING
BREAST CANCER
BREAST CANCER RISK CORRELATED TO:
AGE AT RADIOTHERAPY (<20 YEARS)
NUMBER OF TREATMENTS (>=5)
RADIOTHERAPY YEAR (<1950)