The Epidemiology of Therapy-Related MDS/AML in the Modern ... · Al kyl atin g a e n + t op is m...
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The Epidemiology of Therapy-Related MDS/AML in the Modern Treatment Era July 12, 2019 Lindsay M. Morton, PhD Radiation Epidemiology Branch Division of Cancer Epidemiology and Genetics
Transcript of The Epidemiology of Therapy-Related MDS/AML in the Modern ... · Al kyl atin g a e n + t op is m...
The Epidemiology of Therapy-Related MDS/AML in the
Modern Treatment Era
July 12, 2019
Lindsay M. Morton, PhDRadiation Epidemiology Branch
Division of Cancer Epidemiology and Genetics
2
Growing population of cancer survivors
Bluethmann, Mariotto, Rowland. Cancer Epidemiol Biomarkers Prev 2016
2018,
>16M
3
Treatment-related leukemia
Carey et al. Cancer 1967
4
tMDS/AML risk varies by type of cancer therapy
▪ Leukemogenic treatments
▪ Alkylating agents (melphalan > cyclophosphamide)
▪ Platinum compounds (carboplatin > cisplatin)
▪ Topoisomerase II inhibitors (etoposide > doxorubicin)
▪ Antimetabolites (fludarabine)
▪ Radiotherapy
➢Risks in modern treatment era?
➢New indications for standard agents
➢Novel agents
5
Study designs for investigating tMN risk
CharacteristicClinical trials, Case series, Case-control studies Cancer registry data
Patients Selected Unselected
Sample size Small Large
Follow-up ? Systematic, long-term
Treatment data Detailed Initial treatment yes/no only
tMDS/AML data Detailed Limited
Risk measure Relative risk? Relative & absolute risk
6
SEER: 2000-2014tMDS/AML risks after chemotherapy for adult solid tumors
▪ 17 SEER registries, 2000-2014
▪ 700,612 adults treated with initial chemotherapy for 23 solid tumors
▪ 1619 cases of second primary MDS/AML
Morton et al. JAMA Oncol 2019
▪ Standardized incidence ratios (SIRs)
compared risk with general population
7
▪ SEER-Medicare claims, 2000-2014
▪ 165,820 older adults treated with initial
chemotherapy
▪ Focus on use of known leukemogenic agents
▪ Increased use of platinum-based
chemotherapy
Other specified only (no known leukemogenic agent)
Platinum
Platinum + alkylating agent
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Oral cavity/pharynx (N=5,294)P
erce
nt
of
Pat
ien
ts
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Esophagus (N=3,916)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Stomach (N=4,283)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Colon (N=23,027)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Rectum/rectosigmoid junction (N=10,703)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Anus/anal canal/anorectum (N=1,807)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Peritoneum (N=1,339)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Larynx (N=1,584)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Small cell lung/bronchus (N=7,897)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Non-small cell lung/bronchus (N=34,341)
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Soft Tissue (including heart) (N=596)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Cervix (N=1,472)
Year of diagnosis
Per
cen
tof
Pat
ients
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Corpus uteri (N=4,828)
Year of diagnosis
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Ovary (N=8,814)
Year of diagnosis
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Vagina/vulva (N=635)
Year of diagnosis
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Fallopian tube (N=599)
Year of diagnosis
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Bladder (N=12,251)
Year of diagnosis
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Brain/CNS (N=956)
Year of diagnosis
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Liver (N=2,211)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Female Breast (N=32,592)
Other unspecified only
Topoisomerase II inhibitor
Alkylating agentPlatinum + topoisomerase II inhibitor
Alkylating agent + topoisomerase II inhibitor
Platinum + topoisomerase II inhibitor + alkylating agent
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Pancreas (N=9,698)
Per
cen
to
fP
atie
nts
Other specified only (no known leukemogenic agent)
Platinum
Platinum + alkylating agent
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Oral cavity/pharynx (N=5,294)
Per
cent
of
Pat
ients
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Esophagus (N=3,916)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Stomach (N=4,283)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Colon (N=23,027)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Rectum/rectosigmoid junction (N=10,703)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Anus/anal canal/anorectum (N=1,807)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Peritoneum (N=1,339)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Larynx (N=1,584)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Small cell lung/bronchus (N=7,897)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Non-small cell lung/bronchus (N=34,341)
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Soft Tissue (including heart) (N=596)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Cervix (N=1,472)
Year of diagnosis
Per
cen
tof
Pat
ients
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Corpus uteri (N=4,828)
Year of diagnosis
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Ovary (N=8,814)
Year of diagnosis
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Vagina/vulva (N=635)
Year of diagnosis
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Fallopian tube (N=599)
Year of diagnosis
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Bladder (N=12,251)
Year of diagnosis
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Brain/CNS (N=956)
Year of diagnosis
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Liver (N=2,211)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Female Breast (N=32,592)
Other unspecified only
Topoisomerase II inhibitor
Alkylating agentPlatinum + topoisomerase II inhibitor
Alkylating agent + topoisomerase II inhibitor
Platinum + topoisomerase II inhibitor + alkylating agent
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Pancreas (N=9,698)
Per
cen
to
fP
atie
nts
Other specified only (no known leukemogenic agent)
Platinum
Platinum + alkylating agent
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Oral cavity/pharynx (N=5,294)
Per
cent
of
Pat
ients
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Esophagus (N=3,916)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Stomach (N=4,283)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Colon (N=23,027)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Rectum/rectosigmoid junction (N=10,703)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Anus/anal canal/anorectum (N=1,807)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Peritoneum (N=1,339)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Larynx (N=1,584)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Small cell lung/bronchus (N=7,897)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Non-small cell lung/bronchus (N=34,341)
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Soft Tissue (including heart) (N=596)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Cervix (N=1,472)
Year of diagnosis
Per
cen
to
fP
atie
nts
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Corpus uteri (N=4,828)
Year of diagnosis
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Ovary (N=8,814)
Year of diagnosis
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Vagina/vulva (N=635)
Year of diagnosis
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Fallopian tube (N=599)
Year of diagnosis
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Bladder (N=12,251)
Year of diagnosis
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Brain/CNS (N=956)
Year of diagnosis
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Liver (N=2,211)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Female Breast (N=32,592)
Other unspecified only
Topoisomerase II inhibitor
Alkylating agentPlatinum + topoisomerase II inhibitor
Alkylating agent + topoisomerase II inhibitor
Platinum + topoisomerase II inhibitor + alkylating agent
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Pancreas (N=9,698)
Per
cen
to
fP
atie
nts
Other specified only (no known leukemogenic agent)
Platinum
Platinum + alkylating agent
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Oral cavity/pharynx (N=5,294)
Per
cent
of
Pat
ien
ts
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Esophagus (N=3,916)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Stomach (N=4,283)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Colon (N=23,027)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Rectum/rectosigmoid junction (N=10,703)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Anus/anal canal/anorectum (N=1,807)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Peritoneum (N=1,339)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Larynx (N=1,584)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Small cell lung/bronchus (N=7,897)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Non-small cell lung/bronchus (N=34,341)
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Soft Tissue (including heart) (N=596)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Cervix (N=1,472)
Year of diagnosis
Per
cen
tof
Pat
ients
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Corpus uteri (N=4,828)
Year of diagnosis
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Ovary (N=8,814)
Year of diagnosis
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Vagina/vulva (N=635)
Year of diagnosis
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Fallopian tube (N=599)
Year of diagnosis
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Bladder (N=12,251)
Year of diagnosis
2000 2004 2008 20120
10
20
30
40
50
60
70
80
90
100
Brain/CNS (N=956)
Year of diagnosis
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Liver (N=2,211)
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Female Breast (N=32,592)
Other unspecified only
Topoisomerase II inhibitor
Alkylating agentPlatinum + topoisomerase II inhibitor
Alkylating agent + topoisomerase II inhibitor
Platinum + topoisomerase II inhibitor + alkylating agent
2000 2002 2004 2006 2008 2010 20120
10
20
30
40
50
60
70
80
90
100
Pancreas (N=9,698)
Per
cen
to
fP
atie
nts
Morton et al. JAMA Oncol 2019
SEER: 2000-2014tMDS/AML risks after chemotherapy for adult solid tumors
8
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
SIR
Platinum-based chemotherapy
Morton et al. JAMA Oncol 2019
9
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
SIR
Platinum-based chemotherapy
Morton et al. JAMA Oncol 2019
10
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
SIR
SIR
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
SIR
Platinum-based chemotherapy Akylating agent and/or topoisomerase II-based chemotherapy
Morton et al. JAMA Oncol 2019
11
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
SIR
▪ Expanded patient population at risk
▪ Balance treatment risks/benefits
Platinum-based chemotherapy
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
0.1 1 10 100
Small cell lung/bronchus
Non-small cell lung/bronchus
Ovary
Testis
Oral cavity/pharynx
Esophagus
Stomach
Colon
Rectum/rectosigmoid junction
Pancreas
Peritoneum
Larynx
Bones/joints
Cervix
Corpus uteri
Vagina/vulva
Fallopian tube
Female breast
Soft tissue including heart
Brain/CNS
Anus/anal canal/anorectum
Liver
Bladder
SIR
Akylating agent and/or topoisomerase II-based chemotherapy
Morton et al. JAMA Oncol 2019
12
Role of chemotherapy for childhood cancer in tMDS/AML
▪ Established risk for tMDS/AML after childhood cancer based on small case-control studies
▪ Advances in childhood cancer treatment, risks for current patients?
▪ Initial chemotherapy for childhood cancer
▪ 9 SEER registries, 1975-2015 (N=25,933)
▪ 17 SEER registries, 2000-2015 (N=36,975)
Advani et al. Leukemia (In press)
13
tAML after childhood cancer, 1975-2015
tAML < 5 years after childhood cancer tAML ≥ 5 years after childhood cancer
TotalPtrend<0.001
LymphoidPtrend=0.026
SolidPtrend=0.005
TotalPtrend=0.112
LymphoidPtrend=0.214
SolidPtrend=0.307
Advani et al. Leukemia (In press)
14
1 10 100
Solid cancer
Neuroblastoma
Hepatic tumors
CNS tumors
Medulloblastoma
Glioma
PNET
other
Sarcoma
Osteosarcoma
Ewing
Rhabdomyosarcoma
Other
Germ cell
tMDS/AML after childhood cancer, 2000-2015
1 10 100
Total
Lymphoid cancer
ALL
B-cell ALL
T-cell ALL
Unknown lineage ALL
Hodgkin lymphoma
Other lymphoid neoplasms
All childhood cancers (N=186)
Lymphoid cancer (N=80)
ALL
B-cell ALL
T-cell ALL
Unknown lineage ALL
Hodgkin lymphoma
Other lymphoid neoplasms
Solid cancer (N=106)
Neuroblastoma
Hepatic tumors
CNS tumors
Medulloblastoma
Glioma
PNET
Other CNS tumors
Sarcoma
OsteosarcomaEwing sarcomaRhabdomyosarcoma
Other sarcomas
Germ cell tumors
SIR SIRAdvani et al. Leukemia (In press)
15
tMDS/AML after childhood cancer, 2000-2015
Advani et al. Leukemia (In press)
16
Conclusions
➢Increased risk of tMDS/AML after radiotherapy and chemotherapy in the modern treatment era
➢tMDS/AML is rare
➢Consider gains in survival vs. adverse effects
• Particularly for survivors of first primary cancers with a favorable prognosis
➢Continued efforts to develop effective agents and cancer treatment approaches with fewer late sequelae are critical
➢Need to better understand mechanisms of leukemogenesis
17
Rochelle Curtis, MA
Graça Dores, MD, MPH
Pragati Advani, MD, PhD
Stephen Chanock, MD
Clara Lam, PhD
Martha Linet, MD, MPH
Sara Schonfeld, PhD
Byron Sigel, BA
Jop Teepen, PhD
Margaret Tucker, MD
Acknowledgements
www.cancer.gov www.cancer.gov/espanol
