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Duke Community & Family Medicine Grand Rounds
June 18, 2018
Against the GrainBringing PCPs “back” into Cancer Care through Onco-Primary Care
Kevin C. Oeffinger, MDDirector, Duke Center for Onco-Primary CareProfessor with TenureDepartment of MedicineSecondary: Department of Community & Family Medicine
• Cancer continuum (screening, prevention, cancer care, survivorship)– Current care model in U.S.– Onco-primary care model
• Duke Center for Onco-Primary Care (T+13 months)
Outline
330 MPeople in the U.S., 2016
310 M
151 M
1.6 M1.1 M
Prevention Screening Cancer Therapy Survivorship
2016 Model• Preventiono Lifestyleo (Chemoprevention)o (Genetics)
• Screeningo One-size fits allo Cervicalo Breasto Colono Prostateo Lung
• Survivorshipo One-size fits all
2026 Model• Preventiono Lifestyleo Targeted chemopreventiono Population genetics
• Screeningo Risk-stratifiedo Tumor biomarkerso Expanded cancers
• Survivorshipo Risk-stratifiedo Efficient utilization of
resourceso Coordinated care
Cancer Continuum
Advances in Cancer Screening
Cancer Cases/yr % of total % of deaths
Breast 246,660 14.6% 6.8%Colorectal 134,490 8.0% 8.3%Cervical 12,990 0.8% 0.7%Prostate 180,890 10.7% 4.4%Lung 224,390 13.3% 26.5%Total 47.4% 46.7%
‘Screenable’ Cancers in the U.S.
Cancer Cases/yr % of total % of deaths
%localized
Breast 246,660 14.6% 6.8% 61%Colorectal 134,490 8.0% 8.3% 39%Cervical 12,990 0.8% 0.7% 46%Prostate 180,890 10.7% 4.4% 80%Lung 224,390 13.3% 26.5% 16%Total 47.4% 46.7%
‘Screenable’ Cancers in the U.S.
Cancer Cases/yr % of total % of deaths
%localized
Breast 246,660 14.6% 6.8% 61%Colorectal 134,490 8.0% 8.3% 39%Cervical 12,990 0.8% 0.7% 46%Prostate 180,890 10.7% 4.4% 80%Lung 224,390 13.3% 26.5% 16%Total 47.4% 46.7%
‘Screenable’ Cancers in the U.S.
Key points:• Almost 50% of cancer cases can potentially be detected
by current screening tests• These cancers account for about 50% of cancer deaths• Substantial % of cancers detected at advanced stage• Though not all screen-detected cancers can be cured,
we can do MUCH better
0102030405060708090
100
Cervical Breast Colon Prostate Lung
U.S. Cancer Screening RatesPe
rcen
t
Smith RA, et al. CA Cancer J Clin, 2017
Oeffinger KC, et al. JAMA, 2015
Siu AL, et al. Ann Intern Med, 2016
How does a woman age 40-49
make an informed decision on breast cancer
screening?
If we take 1,000 women at the age of 40 and follow them for 5 years with
an annual mammogram
6 in1000954
in100050 in1000
If we take 1,000 women at the age of 40 and follow them for 5 years with
an annual mammogram
6 in1000954
in100050 in1000
Family History and Breast Density
6 12/1,0006 1/1,000
BRCA1 carrier6 80/1,000
1/12
If we take 1,000 women at the age of 40 and follow them for 5 years with
an annual mammogram
6 in1000954
in100050 in1000
Family History and Breast Density
6 12/1,0006 1/1,000
BRCA1 carrier6 80/1,000
1/12
Risk-Stratified Cancer Screening
No significant difference in prostate cancer deaths between two groups.
However, 90% of control group had undergone PSA testing.
20% reduction in prostate-specific mortalityRate ratio = 0.80 (95% CI 0.65-0.98)
Moyer VA, et al. Ann Intern Med, 2012
USPSTF, JAMA 2018
Negoita S, et al. Cancer, 2018
Prostate Cancer Screening
Duke Primary Care PSA Screening Algorithm
County Practice
Durham
DPC Pickett RoadDPC CroadaileDUC CroasdaileDUC Fayetteville RoadDurham Medical CenterDurham Pediatrics – MainSutton Station Internal MedicineTriangle Family Practice
GranvilleDPC Butner-CreedmoorOxford Family Physicians
Vance DPC Henderson
Alamance
DPC MebaneKernodle Clinic West
Chatham DPC of Galloway Ridge
Orange
DPC HillsboroughDUC HillsboroughDPC MeadowmontDPC Timberlyne
Wake
DPC ApexDPC Blue RidgeDPC Brier CreekDPC Creedmoor RoadDPC MidtownDPC KnightdaleDPC MorrisvilleDPC Waverly PlaceDPC WellesleyDPC Western WakeDPC Wake ForestDPC Wakelon Internal MedicineDUC Brier CreekDUC KnightdaleDUC MorrisvilleNorth Hills Internal Medicine
Duke Primary Care andDuke Primary Care Consortium
224 primary care physicians34 practice sites
7 countiesExpanding sites and physicians
All on same EHR (Epic)Existing research infrastructure
(PBRN)
Duke Primary Care PSA Screening Algorithm
Duke Primary Care PSA Screening Algorithm
Implementation Resulted in Increased Screening
48%
70%
0%10%20%30%40%50%60%70%80%90%
100%
PSA Present
Perc
ent
Change in PSA Testing Pre-Post February 22, 2017
Pre Post
Courtesy of Kevin Shah, MD
Screening increased in all clinics, but rates of screening by clinic vary widely
Courtesy of Kevin Shah, MD
Urology ReferralsFebruary 22, 2017 – February 21, 2018
Age Group Algorithm PSAs UrologyReferrals
%
Urology ReferralsFebruary 22, 2017 – February 21, 2018
Age Group Algorithm PSAs UrologyReferrals
%
Urology ReferralsFebruary 22, 2017 – February 21, 2018
Age Group Algorithm PSAs UrologyReferrals
%
• Rapid uptake using Epic with algorithm embedded in health maintenance / lab results
• Substantial variation in practice• Under and over referrals• Need for efficient and effective informed
decision tool
Key Lessons
Decision Aid
• Development and pilot testing of a CDC-supported patient decision aid for prostate cancer screening.
• Led by John Ragsdale, MD and Sharon Hull, MD
• PCP level approaches– Adding Prostate Health Index (PHI) reflex– Role of Digital Rectal Exams– Alternative referral pathways
• Patient-level approaches– Pre-visit video vignettes via MyChart– Decision aid with visit (upcoming pilot test in 3 sites)– Improved lab result messaging within Epic
• System-level approaches– Nurse navigator (DCI-DPC liaison)– Better tracking of screening to referral to scheduled appointment– Multi-disciplinary quality improvement team– Primary care physician participation in GU oncology tumor board
Potential Approaches to Help
Chemoprevention - 2017
Uptake of SERMs for chemoprevention in clinical practice
Smith SG, et al. Ann Oncol, 2016
• ‘Liquid biopsy’– circulating cell-free DNA (cfDNA) – circulating tumor cells (CTC)
Vockley JG and Niederhuber JE. BMJ, 2015Meyskens FL, et al. J Natl Cancer Inst, 2016Albini A, et al. Clin Cancer Res, 2016
• Epigenetic-marker based system with detection rate of breast cancer similar to mammographyUehiro N, et al. Breast Ca Res, 2016
• Cancer interception Example: ErbB2 inhibition and lapatinib Li D, et al. Oncotarget, 2017
Precision Screening and Chemoprevention
Bradshaw PT, et al. Epidem, 2016
Hanrahan EO, et al. J Clin Oncol, 2007
Probability of death from breast cancer or other causes among women age 50 and older
with ER+ early stage breast cancerSEER: 1988-2001
0
20
40
60
80
100
Perc
ent
HTN Lipids DM
Chen J, et al. J Am Coll Cardiol, 2012
Percent of women with early stage breast cancer
and a cardiovascular risk factorSEER-Medicare: 2000-2007
Importance of Non-Cancer Comorbidities
Percent of breast cancer survivors adherent to their statin therapy prior to and following early stage breast cancer diagnosis and treatment
(Group Health 1990-2008, N=4,221 women)
Calip GS, et al. Breast Cancer Res Treat, 2013
0102030405060708090
100
Year - 1 Treatmentperiod
Year + 1 Year + 2 Year + 3
Perc
ent
Presented by: Kevin C. Oeffinger, MD
Predictors of nonadherence to medications among breast cancer survivors
(Group Health 1990-2008, N=2,308)
Calip GS, et al. Breast Cancer Res Treat, 2017
Presented by: Kevin C. Oeffinger, MD
Importance of Non-Cancer Comorbidities
• Most women with breast cancer will not die of breast cancer
• Continued monitoring and management of common comorbidities may be as important for longevity / QoL as treatment of the breast cancer
• Lack of standardized approaches to manage hypertension, diabetes, and lipid disorders
Management of Comorbidities• Hypertension (pre/during/post cancer) is a key
risk factor in development of heart failure in cancer survivors treated with cardiotoxic therapy– Jawa Z, et al. Medicine, 2016– Chen J, et al. J Am Coll Cardiol, 2012– Salz T, et al. J Clin Oncol, 2017
• Studies pre new AHA / ACC guidelines for HTN
• Diagnosed at age 42• Invasive ductal carcinoma• ER- PR- HER2+ • T2N1• Trastuzumab• 50 Gy to Right breast
47-year-old breast cancer survivor
150
100
50
6/13 6/14 6/15 6/16 6/18
• Diagnosed at age 42• Invasive ductal carcinoma• ER- PR- HER2+ • T2N1• Trastuzumab• 50 Gy to Right breast
47-year-old breast cancer survivor
Lipid profile•Total = 247•LDL = 188•HDL = 51•TG = 40
Statin therapy?
10-year risk = 1.8%
Chronic Cancer Patient
• Increasing number of patients with advanced cancer are now being treated as chronic cancer patients
• Management of comorbidities remains essential in this population
• ‘Cure the cancer, lose the patient’
• Randomized controlled trial• Population: Breast and prostate cancer patients receiving
cardiotoxic therapy• Primary outcome – blood pressure control• Intervention: automated text alert to patient and Epic
message to PCP when BP is above threshold• Control – usual care• Team: oncology, cardiology, primary care, population
health science, biostatistics, onco-primary care• Overarching goals:
– Blood pressure management and prevention of cardiotoxicity– Re-engage PCPs in the care of patients on therapy
Future Study
De Moor JS, et al. Cancer Epidemiol Biomarkers Prev, 2013
Cancer Survivors in the United States
There are now 14.5 million survivors in the USBy 2020, there will be almost 18 million survivors
Late Mortality Among 5+ Year SurvivorsChildhood Cancer Survivor Study (N=20,483)
Causes SMRSecond cancers 15.2 Cardiac 7.0Pulmonary 8.8
Mertens AC, et al. J Natl Cancer Inst, 2009
Armstrong GT, et al. J Clin Oncol, 2009
Cumulative Cause-Specific MortalityChildhood Cancer Survivor Study
Late Mortality Among 5+ Year HL SurvivorsMSKCC Hodgkin Lymphoma Study (1975-2000; N=747)
Matasar M, et al. J Natl Cancer Inst, 2015
Cumulative Incidence by Causes of Death for Patients With Stage I Testicular Seminoma
Beard CJ, et al. Cancer 2013
SEER Registry: N=9193 men; Diagnosed 1973-2001
Probability of death from breast cancer or other causes among women age 50 and older
with ER+ early stage breast cancerSEER: 1988-2001
Hanrahan EO, et al. J Clin Oncol, 2007
0
0.1
0.2
0.3
0.4
0.5
0.6
0.7
0.8
0.9
1
0 5 10 15 20 25 30
73.4% with at least one chronic condition
42.4% with a severe orlife-threateningcondition or death
Cum
ulat
ive
Inci
denc
e
Years since Cancer
Cumulative incidence of chronic physical health conditions among 10,397 young adult survivors of childhood cancer
Childhood Cancer Survivor Study
Oeffinger KC, et al. N Engl J Med, 2006
Fig 1a
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0.6347982037
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Fig 1a CI
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yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors, by GRADE 1-5
0.3732219061
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all_survivors
yrsci6lcl6ucl6ci7lcl7ucl7
50.37322190610.36428352460.38216028760.15033783780.1437327940.1569428817
50.37322190610.36428352460.38216028760.15033783780.1437327940.1569428817
50.38862217620.37961363060.39763072180.15827202010.1515260960.1650179441
60.38862217620.37961363060.39763072180.15827202010.1515260960.1650179441
60.40487649950.39580321340.41394978560.16642642340.15954093710.1733119098
70.40487649950.39580321340.41394978560.16642642340.15954093710.1733119098
70.42022159160.41109539990.42934778330.17273771020.16574741930.179728001
80.42022159160.41109539990.42934778330.17273771020.16574741930.179728001
80.43837787230.42919878840.44755695610.18229846720.17515375780.1894431767
90.43837787230.42919878840.44755695610.18229846720.17515375780.1894431767
90.45593157380.44670799810.46515514950.18967194920.18240900770.1969348907
100.45593157380.44670799810.46515514950.18967194920.18240900770.1969348907
100.47354718660.46428139880.48281297430.20012933260.19269717120.207561494
110.47354718660.46428139880.48281297430.20012933260.19269717120.207561494
110.48929998950.47999564090.49860433810.20948832440.20190108940.2170755593
120.48929998950.47999564090.49860433810.20948832440.20190108940.2170755593
120.5059243950.4965755690.5152732210.21906319540.21131153330.2268148575
130.5059243950.4965755690.5152732210.21906319540.21131153330.2268148575
130.52223797810.51283859240.53163736380.22815880190.22024229980.236075304
140.52223797810.51283859240.53163736380.22815880190.22024229980.236075304
140.53807508610.5286162080.54753396420.23917248260.23104161320.2473033519
150.53807508610.5286162080.54753396420.23917248260.23104161320.2473033519
150.55443214030.54489172730.56397255330.24912656420.24078367080.2574694577
160.55443214030.54489172730.56397255330.24912656420.24078367080.2574694577
160.56771755190.55808936250.57734574130.25802678880.24946930770.26658427
170.56771755190.55808936250.57734574130.25802678880.24946930770.26658427
170.58195898570.57220284490.59171512640.26706168370.25825033630.2758730312
180.58195898570.57220284490.59171512640.26706168370.25825033630.2758730312
180.59510194020.58519052410.60501335640.27590264220.26680203580.2850032486
190.59510194020.58519052410.60501335640.27590264220.26680203580.2850032486
190.6079369820.59782108340.61805288060.28487194180.27542580490.2943180787
200.6079369820.59782108340.61805288060.28487194180.27542580490.2943180787
200.62323207350.61279982180.63366432530.29459541680.28469774730.3044930863
210.62323207350.61279982180.63366432530.29459541680.28469774730.3044930863
210.63479820370.62404084950.64555555780.30540321960.29488309750.3159233417
220.63479820370.62404084950.64555555780.30540321960.29488309750.3159233417
220.64129064230.63027737260.6523039120.31591592890.30464152430.3271903334
230.64129064230.63027737260.6523039120.31591592890.30464152430.3271903334
230.65707373130.64514392620.66900353650.32162194210.30977347640.3334704078
240.65707373130.64514392620.66900353650.32162194210.30977347640.3334704078
240.66809684110.65508426160.68110942060.33107021090.31771220150.3444282202
250.66809684110.65508426160.68110942060.33107021090.31771220150.3444282202
250.68028027820.66505941860.69550113790.3359385090.32108154370.3507954743
260.68028027820.66505941860.69550113790.3359385090.32108154370.3507954743
260.69556632980.67533181750.71580084210.35589853120.33194208070.3798549817
270.69556632980.67533181750.71580084210.35589853120.33194208070.3798549817
270.71419620510.68381134360.74458106660.38168022650.34013437150.4232260815
280.71419620510.68381134360.74458106660.38168022650.34013437150.4232260815
280.73437857010.68951200660.77924513350.42422002380.33651863820.5119214094
290.73437857010.68951200660.77924513350.42422002380.33651863820.5119214094
290.73437857010.68951200660.77924513350.42422002380.33651863820.5119214094
300.73437857010.68951200660.77924513350.42422002380.33651863820.5119214094
30
31
31
&A
Page &P
Fig 1b
55
55
55
66
66
77
77
88
88
99
99
1010
1010
1111
1111
1212
1212
1313
1313
1414
1414
1515
1515
1616
1616
1717
1717
1818
1818
1919
1919
2020
2020
2121
2121
2222
2222
2323
2323
2424
2424
2525
2525
2626
2626
2727
2727
2828
GRADE 1-5
GRADE 3-5
yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors for GRADE 1-5 and GRADE 3-5Leukemia
0.242835131
0.0696456086
0.242835131
0.0696456086
0.2607380718
0.0773703202
0.2607380718
0.0773703202
0.2774629736
0.0832730834
0.2774629736
0.0832730834
0.2923950158
0.0892086056
0.2923950158
0.0892086056
0.3114660333
0.0964649519
0.3114660333
0.0964649519
0.3330805294
0.1019340786
0.3330805294
0.1019340786
0.354884485
0.1099018049
0.354884485
0.1099018049
0.3717359481
0.1147441624
0.3717359481
0.1147441624
0.3904167122
0.1209369611
0.3904167122
0.1209369611
0.4077446823
0.1259978646
0.4077446823
0.1259978646
0.4265295428
0.1345062006
0.4265295428
0.1345062006
0.4479583916
0.1411943675
0.4479583916
0.1411943675
0.4600227492
0.1456668106
0.4600227492
0.1456668106
0.4801558986
0.1530380939
0.4801558986
0.1530380939
0.4933615422
0.157708444
0.4933615422
0.157708444
0.5102727242
0.1624773967
0.5102727242
0.1624773967
0.5318896264
0.1695781624
0.5318896264
0.1695781624
0.5538872568
0.1776735389
0.5538872568
0.1776735389
0.5634135149
0.1869082648
0.5634135149
0.1869082648
0.5756200422
0.1977773542
0.5756200422
0.1977773542
0.604821002
0.2111757286
0.604821002
0.2111757286
0.6281817698
0.2268579168
0.6281817698
0.2268579168
0.679575459
0.2268579168
0.679575459
0.2268579168
0.679575459
0.2268579168
0.679575459
0.2268579168
Fig 1b CI
555555
555555
555555
666666
666666
777777
777777
888888
888888
999999
999999
101010101010
101010101010
111111111111
111111111111
121212121212
121212121212
131313131313
131313131313
141414141414
141414141414
151515151515
151515151515
161616161616
161616161616
171717171717
171717171717
181818181818
181818181818
191919191919
191919191919
202020202020
202020202020
212121212121
212121212121
222222222222
222222222222
232323232323
232323232323
242424242424
242424242424
252525252525
252525252525
262626262626
262626262626
272727272727
272727272727
282828282828
GRADE 1-5
GRADE 3-5
Leuk-L
Leuk-L
Leuk-U
Leuk-U
yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors for GRADE 1-5 and GRADE 3-5Leukemia
0.242835131
0.0696456086
0.0608873091
0.2280814732
0.0784039082
0.2575887888
0.242835131
0.0696456086
0.0608873091
0.2280814732
0.0784039082
0.2575887888
0.2607380718
0.0773703202
0.068176166
0.2456309275
0.0865644743
0.2758452161
0.2607380718
0.0773703202
0.068176166
0.2456309275
0.0865644743
0.2758452161
0.2774629736
0.0832730834
0.0737623511
0.262053062
0.0927838156
0.2928728853
0.2774629736
0.0832730834
0.0737623511
0.262053062
0.0927838156
0.2928728853
0.2923950158
0.0892086056
0.0793921103
0.2767352702
0.0990251009
0.3080547613
0.2923950158
0.0892086056
0.0793921103
0.2767352702
0.0990251009
0.3080547613
0.3114660333
0.0964649519
0.0862885681
0.2955137759
0.1066413356
0.3274182907
0.3114660333
0.0964649519
0.0862885681
0.2955137759
0.1066413356
0.3274182907
0.3330805294
0.1019340786
0.0914924724
0.316822863
0.1123756848
0.3493381957
0.3330805294
0.1019340786
0.0914924724
0.316822863
0.1123756848
0.3493381957
0.354884485
0.1099018049
0.099077185
0.3383413388
0.1207264247
0.3714276311
0.354884485
0.1099018049
0.099077185
0.3383413388
0.1207264247
0.3714276311
0.3717359481
0.1147441624
0.1036852387
0.354978655
0.1258030861
0.3884932412
0.3717359481
0.1147441624
0.1036852387
0.354978655
0.1258030861
0.3884932412
0.3904167122
0.1209369611
0.1095703678
0.3734200914
0.1323035544
0.407413333
0.3904167122
0.1209369611
0.1095703678
0.3734200914
0.1323035544
0.407413333
0.4077446823
0.1259978646
0.1143685969
0.3905100196
0.1376271324
0.4249793451
0.4077446823
0.1259978646
0.1143685969
0.3905100196
0.1376271324
0.4249793451
0.4265295428
0.1345062006
0.1224072454
0.4090088126
0.1466051559
0.444050273
0.4265295428
0.1345062006
0.1224072454
0.4090088126
0.1466051559
0.444050273
0.4479583916
0.1411943675
0.1286922013
0.4300562064
0.1536965338
0.4658605768
0.4479583916
0.1411943675
0.1286922013
0.4300562064
0.1536965338
0.4658605768
0.4600227492
0.1456668106
0.1328516171
0.4418481766
0.158482004
0.4781973218
0.4600227492
0.1456668106
0.1328516171
0.4418481766
0.158482004
0.4781973218
0.4801558986
0.1530380939
0.1396141603
0.4614129072
0.1664620276
0.49889889
0.4801558986
0.1530380939
0.1396141603
0.4614129072
0.1664620276
0.49889889
0.4933615422
0.157708444
0.143848742
0.4741845039
0.171568146
0.5125385804
0.4933615422
0.157708444
0.143848742
0.4741845039
0.171568146
0.5125385804
0.5102727242
0.1624773967
0.1480804469
0.4903688644
0.1768743464
0.5301765839
0.5102727242
0.1624773967
0.1480804469
0.4903688644
0.1768743464
0.5301765839
0.5318896264
0.1695781624
0.1542248735
0.5108543365
0.1849314514
0.5529249162
0.5318896264
0.1695781624
0.1542248735
0.5108543365
0.1849314514
0.5529249162
0.5538872568
0.1776735389
0.1609135402
0.5312938039
0.1944335377
0.5764807097
0.5538872568
0.1776735389
0.1609135402
0.5312938039
0.1944335377
0.5764807097
0.5634135149
0.1869082648
0.1680568943
0.5398398847
0.2057596352
0.5869871451
0.5634135149
0.1869082648
0.1680568943
0.5398398847
0.2057596352
0.5869871451
0.5756200422
0.1977773542
0.175536397
0.549901356
0.2200183114
0.6013387285
0.5756200422
0.1977773542
0.175536397
0.549901356
0.2200183114
0.6013387285
0.604821002
0.2111757286
0.1826128901
0.5706685904
0.239738567
0.6389734136
0.604821002
0.2111757286
0.1826128901
0.5706685904
0.239738567
0.6389734136
0.6281817698
0.2268579168
0.1855685156
0.5836742274
0.268147318
0.6726893122
0.6281817698
0.2268579168
0.1855685156
0.5836742274
0.268147318
0.6726893122
0.679575459
0.2268579168
0.1855685156
0.5819404382
0.268147318
0.7772104799
0.679575459
0.2268579168
0.1855685156
0.5819404382
0.268147318
0.7772104799
0.679575459
0.2268579168
0.1855685156
0.5819404382
0.268147318
0.7772104799
0.679575459
0.2268579168
0.1855685156
0.5819404382
0.268147318
0.7772104799
Fig 1c
55
55
55
66
66
77
77
88
88
99
99
1010
1010
1111
1111
1212
1212
1313
1313
1414
1414
1515
1515
1616
1616
1717
1717
1818
1818
1919
1919
2020
2020
2121
2121
2222
2222
2323
2323
2424
2424
2525
2525
2626
2626
2727
2727
2828
GRADE 1-5
GRADE 3-5
yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors for GRADE 1-5 and GRADE 3-5CNS
0.5799055968
0.2070128119
0.5799055968
0.2070128119
0.5879973028
0.2157863062
0.5879973028
0.2157863062
0.5974852247
0.2225646447
0.5974852247
0.2225646447
0.6029547045
0.2287253878
0.6029547045
0.2287253878
0.6139334422
0.2397988412
0.6139334422
0.2397988412
0.6216592705
0.2462346771
0.6216592705
0.2462346771
0.6312796298
0.2590800863
0.6312796298
0.2590800863
0.6398122377
0.2647724248
0.6398122377
0.2647724248
0.6497226913
0.2736349383
0.6497226913
0.2736349383
0.6594074564
0.2851727833
0.6594074564
0.2851727833
0.6642126376
0.2915922642
0.6642126376
0.2915922642
0.6693583434
0.299775121
0.6693583434
0.299775121
0.6748186339
0.3114231672
0.6748186339
0.3114231672
0.6772504333
0.3158674342
0.6772504333
0.3158674342
0.6840990252
0.3313240443
0.6840990252
0.3313240443
0.690222472
0.3393720115
0.690222472
0.3393720115
0.6995607284
0.3418749679
0.6995607284
0.3418749679
0.7016466766
0.3507167722
0.7016466766
0.3507167722
0.7016466766
0.3545226932
0.7016466766
0.3545226932
0.708984681
0.3545226932
0.708984681
0.3545226932
0.7159150186
0.3634444801
0.7159150186
0.3634444801
0.7263105249
0.3634444801
0.7263105249
0.3634444801
0.7263105249
0.3970441584
0.7263105249
0.3970441584
0.7263105249
0.3970441584
0.7263105249
0.3970441584
Fig 1c CI
555555
555555
555555
666666
666666
777777
777777
888888
888888
999999
999999
101010101010
101010101010
111111111111
111111111111
121212121212
121212121212
131313131313
131313131313
141414141414
141414141414
151515151515
151515151515
161616161616
161616161616
171717171717
171717171717
181818181818
181818181818
191919191919
191919191919
202020202020
202020202020
212121212121
212121212121
222222222222
222222222222
232323232323
232323232323
242424242424
242424242424
252525252525
252525252525
262626262626
262626262626
272727272727
272727272727
282828282828
GRADE 1-5
GRADE 3-5
CNS-L
CNS-U
CNS-L
CNS-U
yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors for GRADE 1-5 and GRADE 3-5CNS
0.5799055968
0.2070128119
0.1863914571
0.2276341666
0.554784558
0.6050266355
0.5799055968
0.2070128119
0.1863914571
0.2276341666
0.554784558
0.6050266355
0.5879973028
0.2157863062
0.1948488389
0.2367237735
0.5629464109
0.6130481946
0.5879973028
0.2157863062
0.1948488389
0.2367237735
0.5629464109
0.6130481946
0.5974852247
0.2225646447
0.2013908386
0.2437384509
0.5725230644
0.622447385
0.5974852247
0.2225646447
0.2013908386
0.2437384509
0.5725230644
0.622447385
0.6029547045
0.2287253878
0.2073402286
0.250110547
0.5780456607
0.6278637483
0.6029547045
0.2287253878
0.2073402286
0.250110547
0.5780456607
0.6278637483
0.6139334422
0.2397988412
0.2180432513
0.2615544311
0.5891390737
0.6387278107
0.6139334422
0.2397988412
0.2180432513
0.2615544311
0.5891390737
0.6387278107
0.6216592705
0.2462346771
0.2242607098
0.2682086444
0.5969443304
0.6463742105
0.6216592705
0.2462346771
0.2242607098
0.2682086444
0.5969443304
0.6463742105
0.6312796298
0.2590800863
0.2366482903
0.2815118824
0.6066462299
0.6559130298
0.6312796298
0.2590800863
0.2366482903
0.2815118824
0.6066462299
0.6559130298
0.6398122377
0.2647724248
0.242120161
0.2874246886
0.615238629
0.6643858464
0.6398122377
0.2647724248
0.242120161
0.2874246886
0.615238629
0.6643858464
0.6497226913
0.2736349383
0.2505996417
0.296670235
0.6251949008
0.6742504819
0.6497226913
0.2736349383
0.2505996417
0.296670235
0.6251949008
0.6742504819
0.6594074564
0.2851727833
0.261597324
0.3087482426
0.634901328
0.6839135849
0.6594074564
0.2851727833
0.261597324
0.3087482426
0.634901328
0.6839135849
0.6642126376
0.2915922642
0.2676762458
0.3155082826
0.6396946447
0.6887306305
0.6642126376
0.2915922642
0.2676762458
0.3155082826
0.6396946447
0.6887306305
0.6693583434
0.299775121
0.275380666
0.3241695761
0.6448072357
0.6939094511
0.6693583434
0.299775121
0.275380666
0.3241695761
0.6448072357
0.6939094511
0.6748186339
0.3114231672
0.2862788805
0.336567454
0.6502146753
0.6994225924
0.6748186339
0.3114231672
0.2862788805
0.336567454
0.6502146753
0.6994225924
0.6772504333
0.3158674342
0.290389289
0.3413455795
0.6526029197
0.701897947
0.6772504333
0.3158674342
0.290389289
0.3413455795
0.6526029197
0.701897947
0.6840990252
0.3313240443
0.3045048012
0.3581432873
0.6592631913
0.708934859
0.6840990252
0.3313240443
0.3045048012
0.3581432873
0.6592631913
0.708934859
0.690222472
0.3393720115
0.3117483471
0.3669956759
0.6651662538
0.7152786902
0.690222472
0.3393720115
0.3117483471
0.3669956759
0.6651662538
0.7152786902
0.6995607284
0.3418749679
0.3139269053
0.3698230305
0.6739915243
0.7251299325
0.6995607284
0.3418749679
0.3139269053
0.3698230305
0.6739915243
0.7251299325
0.7016466766
0.3507167722
0.3214228749
0.3800106694
0.6759412062
0.727352147
0.7016466766
0.3507167722
0.3214228749
0.3800106694
0.6759412062
0.727352147
0.7016466766
0.3545226932
0.3244747467
0.3845706397
0.6759412062
0.727352147
0.7016466766
0.3545226932
0.3244747467
0.3845706397
0.6759412062
0.727352147
0.708984681
0.3545226932
0.3244747467
0.3845706397
0.682044836
0.7359245261
0.708984681
0.3545226932
0.3244747467
0.3845706397
0.682044836
0.7359245261
0.7159150186
0.3634444801
0.3291398806
0.3977490797
0.6865523377
0.7452776995
0.7159150186
0.3634444801
0.3291398806
0.3977490797
0.6865523377
0.7452776995
0.7263105249
0.3634444801
0.3291398806
0.3977490797
0.692243669
0.7603773809
0.7263105249
0.3634444801
0.3291398806
0.3977490797
0.692243669
0.7603773809
0.7263105249
0.3970441584
0.3260989536
0.4679893633
0.692243669
0.7603773809
0.7263105249
0.3970441584
0.3260989536
0.4679893633
0.692243669
0.7603773809
0.7263105249
0.3970441584
0.3260989536
0.4679893633
0.692243669
0.7603773809
0.7263105249
0.3970441584
0.3260989536
0.4679893633
0.692243669
0.7603773809
Fig 1d
55
55
55
66
66
77
77
88
88
99
99
1010
1010
1111
1111
1212
1212
1313
1313
1414
1414
1515
1515
1616
1616
1717
1717
1818
1818
1919
1919
2020
2020
2121
2121
2222
2222
2323
2323
2424
2424
2525
2525
2626
2626
2727
2727
2828
GRADE 1-5
GRADE 3-5
yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors for GRADE 1-5 and GRADE 3-5HD
0.369451074
0.092124105
0.369451074
0.092124105
0.3904534606
0.1031374962
0.3904534606
0.1031374962
0.4115061323
0.116639882
0.4115061323
0.116639882
0.4283368699
0.1239259244
0.4283368699
0.1239259244
0.4542301155
0.1357514734
0.4542301155
0.1357514734
0.4736115167
0.1479351553
0.4736115167
0.1479351553
0.4967925512
0.1654142045
0.4967925512
0.1654142045
0.5232639898
0.1896395927
0.5232639898
0.1896395927
0.5442729895
0.208137346
0.5442729895
0.208137346
0.5689631142
0.2256400757
0.5689631142
0.2256400757
0.587623008
0.247492698
0.587623008
0.247492698
0.6138203958
0.2695954543
0.6138203958
0.2695954543
0.6317319167
0.2890154716
0.6317319167
0.2890154716
0.6466497272
0.307087583
0.6466497272
0.307087583
0.6605437665
0.3220329966
0.6605437665
0.3220329966
0.6710714086
0.3437266412
0.6710714086
0.3437266412
0.6851082647
0.3604255292
0.6851082647
0.3604255292
0.6927861423
0.3751454905
0.6927861423
0.3751454905
0.6943194122
0.3954319418
0.6943194122
0.3954319418
0.7153498174
0.4007262108
0.7153498174
0.4007262108
0.7205565715
0.4137668312
0.7205565715
0.4137668312
0.7300233971
0.4137668312
0.7300233971
0.4137668312
0.7450125376
0.4402048063
0.7450125376
0.4402048063
0.7674962485
0.5062997443
0.7674962485
0.5062997443
Fig 1d CI
555555
555555
555555
666666
666666
777777
777777
888888
888888
999999
999999
101010101010
101010101010
111111111111
111111111111
121212121212
121212121212
131313131313
131313131313
141414141414
141414141414
151515151515
151515151515
161616161616
161616161616
171717171717
171717171717
181818181818
181818181818
191919191919
191919191919
202020202020
202020202020
212121212121
212121212121
222222222222
222222222222
232323232323
232323232323
242424242424
242424242424
252525252525
252525252525
262626262626
262626262626
272727272727
272727272727
282828282828
GRADE 1-5
GRADE 3-5
HD-L
HD-L
HD-U
HD-U
yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors for GRADE 1-5 and GRADE 3-5HD
0.369451074
0.092124105
0.0797400195
0.348782909
0.1045081905
0.390119239
0.369451074
0.092124105
0.0797400195
0.348782909
0.1045081905
0.390119239
0.3904534606
0.1031374962
0.0901113368
0.3695628021
0.1161636556
0.4113441192
0.3904534606
0.1031374962
0.0901113368
0.3695628021
0.1161636556
0.4113441192
0.4115061323
0.116639882
0.1028831721
0.3904311708
0.130396592
0.4325810938
0.4115061323
0.116639882
0.1028831721
0.3904311708
0.130396592
0.4325810938
0.4283368699
0.1239259244
0.1097971713
0.407139827
0.1380546775
0.4495339127
0.4283368699
0.1239259244
0.1097971713
0.407139827
0.1380546775
0.4495339127
0.4542301155
0.1357514734
0.1210426071
0.4328776703
0.1504603397
0.4755825607
0.4542301155
0.1357514734
0.1210426071
0.4328776703
0.1504603397
0.4755825607
0.4736115167
0.1479351553
0.1326473025
0.4521685145
0.1632230081
0.4950545189
0.4736115167
0.1479351553
0.1326473025
0.4521685145
0.1632230081
0.4950545189
0.4967925512
0.1654142045
0.1493188693
0.4752511139
0.1815095396
0.5183339886
0.4967925512
0.1654142045
0.1493188693
0.4752511139
0.1815095396
0.5183339886
0.5232639898
0.1896395927
0.1724602642
0.5016192794
0.2068189212
0.5449087003
0.5232639898
0.1896395927
0.1724602642
0.5016192794
0.2068189212
0.5449087003
0.5442729895
0.208137346
0.1901591804
0.5225512181
0.2261155116
0.565994761
0.5442729895
0.208137346
0.1901591804
0.5225512181
0.2261155116
0.565994761
0.5689631142
0.2256400757
0.2068875031
0.5471472494
0.2443926483
0.5907789791
0.5689631142
0.2256400757
0.2068875031
0.5471472494
0.2443926483
0.5907789791
0.587623008
0.247492698
0.2277572041
0.5657255105
0.2672281919
0.6095205055
0.587623008
0.247492698
0.2277572041
0.5657255105
0.2672281919
0.6095205055
0.6138203958
0.2695954543
0.2488694156
0.5918000502
0.290321493
0.6358407414
0.6138203958
0.2695954543
0.2488694156
0.5918000502
0.290321493
0.6358407414
0.6317319167
0.2890154716
0.26738038
0.6096126736
0.3106505632
0.6538511597
0.6317319167
0.2890154716
0.26738038
0.6096126736
0.3106505632
0.6538511597
0.6466497272
0.307087583
0.2845363216
0.6243972667
0.3296388445
0.6689021878
0.6466497272
0.307087583
0.2845363216
0.6243972667
0.3296388445
0.6689021878
0.6605437665
0.3220329966
0.2986584373
0.6381078018
0.3454075558
0.6829797311
0.6605437665
0.3220329966
0.2986584373
0.6381078018
0.3454075558
0.6829797311
0.6710714086
0.3437266412
0.3190652597
0.6484289965
0.3683880227
0.6937138206
0.6710714086
0.3437266412
0.3190652597
0.6484289965
0.3683880227
0.6937138206
0.6851082647
0.3604255292
0.33466811
0.6621325759
0.3861829484
0.7080839535
0.6851082647
0.3604255292
0.33466811
0.6621325759
0.3861829484
0.7080839535
0.6927861423
0.3751454905
0.3482732273
0.6696028335
0.4020177538
0.7159694512
0.6927861423
0.3751454905
0.3482732273
0.6696028335
0.4020177538
0.7159694512
0.6943194122
0.3954319418
0.3666967734
0.6710670441
0.4241671101
0.7175717803
0.6943194122
0.3954319418
0.3666967734
0.6710670441
0.4241671101
0.7175717803
0.7153498174
0.4007262108
0.3713411652
0.6908126012
0.4301112563
0.7398870336
0.7153498174
0.4007262108
0.3713411652
0.6908126012
0.4301112563
0.7398870336
0.7205565715
0.4137668312
0.3816002645
0.6955237477
0.4459333978
0.7455893953
0.7205565715
0.4137668312
0.3816002645
0.6955237477
0.4459333978
0.7455893953
0.7300233971
0.4137668312
0.3816002645
0.7029167023
0.4459333978
0.7571300919
0.7300233971
0.4137668312
0.3816002645
0.7029167023
0.4459333978
0.7571300919
0.7450125376
0.4402048063
0.3934731813
0.7135275515
0.4869364314
0.7764975238
0.7450125376
0.4402048063
0.3934731813
0.7135275515
0.4869364314
0.7764975238
0.7674962485
0.5062997443
0.4150868077
0.7224249271
0.5975126808
0.8125675699
0.7674962485
0.5062997443
0.4150868077
0.7224249271
0.5975126808
0.8125675699
Fig 1e
55
55
55
66
66
77
77
88
88
99
99
1010
1010
1111
1111
1212
1212
1313
1313
1414
1414
1515
1515
1616
1616
1717
1717
1818
1818
1919
1919
2020
2020
2121
2121
2222
2222
2323
2323
2424
2424
2525
2525
2626
2626
2727
2727
2828
GRADE 1-5
GRADE 3-5
yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors for GRADE 1-5 and GRADE 3-5NHL
0.3381147541
0.1178278689
0.3381147541
0.1178278689
0.3504098361
0.1239825665
0.3504098361
0.1239825665
0.36891157
0.1322278146
0.36891157
0.1322278146
0.3957250832
0.1384266517
0.3957250832
0.1384266517
0.4165321085
0.1436367173
0.4165321085
0.1436367173
0.4378075846
0.1522067435
0.4378075846
0.1522067435
0.452198801
0.1577786984
0.452198801
0.1577786984
0.4652477288
0.1649185195
0.4652477288
0.1649185195
0.4833501503
0.1713657554
0.4833501503
0.1713657554
0.4989591356
0.1784838677
0.4989591356
0.1784838677
0.5205666152
0.1894281402
0.5205666152
0.1894281402
0.531170622
0.1965672612
0.531170622
0.1965672612
0.5391036347
0.2007221528
0.5391036347
0.2007221528
0.5460612769
0.2129014279
0.5460612769
0.2129014279
0.5542169238
0.2188687835
0.5542169238
0.2188687835
0.5674471953
0.229725235
0.5674471953
0.229725235
0.5960772184
0.2479806694
0.5960772184
0.2479806694
0.6012049838
0.2539732141
0.6012049838
0.2539732141
0.6135890208
0.2539732141
0.6135890208
0.2539732141
0.6135890208
0.2539732141
0.6135890208
0.2539732141
0.6252060285
0.2539732141
0.6252060285
0.2539732141
0.6252060285
0.2539732141
0.6252060285
0.2539732141
0.6613478303
0.2539732141
0.6613478303
0.2539732141
0.6613478303
0.2539732141
0.6613478303
0.2539732141
Fig 1e CI
555555
555555
555555
666666
666666
777777
777777
888888
888888
999999
999999
101010101010
101010101010
111111111111
111111111111
121212121212
121212121212
131313131313
131313131313
141414141414
141414141414
151515151515
151515151515
161616161616
161616161616
171717171717
171717171717
181818181818
181818181818
191919191919
191919191919
202020202020
202020202020
212121212121
212121212121
222222222222
222222222222
232323232323
232323232323
242424242424
242424242424
252525252525
252525252525
262626262626
262626262626
272727272727
272727272727
282828282828
NHL-L
NHL-L
NHL-U
NHL-U
GRADE 1-5
GRADE 3-5
yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors for GRADE 1-5 and GRADE 3-5NHL
0.0976008518
0.3084353912
0.1380548859
0.367794117
0.3381147541
0.1178278689
0.0976008518
0.3084353912
0.1380548859
0.367794117
0.3381147541
0.1178278689
0.1033058262
0.3204776093
0.1446593067
0.3803420628
0.3504098361
0.1239825665
0.1033058262
0.3204776093
0.1446593067
0.3803420628
0.3504098361
0.1239825665
0.110970905
0.3386360844
0.1534847241
0.3991870555
0.36891157
0.1322278146
0.110970905
0.3386360844
0.1534847241
0.3991870555
0.36891157
0.1322278146
0.1167506159
0.3650316574
0.1601026875
0.426418509
0.3957250832
0.1384266517
0.1167506159
0.3650316574
0.1601026875
0.426418509
0.3957250832
0.1384266517
0.1216159342
0.3855705494
0.1656575003
0.4474936676
0.4165321085
0.1436367173
0.1216159342
0.3855705494
0.1656575003
0.4474936676
0.4165321085
0.1436367173
0.1296197336
0.4066025949
0.1747937534
0.4690125744
0.4378075846
0.1522067435
0.1296197336
0.4066025949
0.1747937534
0.4690125744
0.4378075846
0.1522067435
0.1348181808
0.4208274374
0.180739216
0.4835701647
0.452198801
0.1577786984
0.1348181808
0.4208274374
0.180739216
0.4835701647
0.452198801
0.1577786984
0.1414526883
0.4336903789
0.1883843507
0.4968050786
0.4652477288
0.1649185195
0.1414526883
0.4336903789
0.1883843507
0.4968050786
0.4652477288
0.1649185195
0.1474103358
0.4514690195
0.195321175
0.5152312812
0.4833501503
0.1713657554
0.1474103358
0.4514690195
0.195321175
0.5152312812
0.4833501503
0.1713657554
0.1539352907
0.46673576
0.2030324447
0.5311825113
0.4989591356
0.1784838677
0.1539352907
0.46673576
0.2030324447
0.5311825113
0.4989591356
0.1784838677
0.1639032688
0.4878088767
0.2149530116
0.5533243538
0.5205666152
0.1894281402
0.1639032688
0.4878088767
0.2149530116
0.5533243538
0.5205666152
0.1894281402
0.1703263387
0.4980596387
0.2228081836
0.5642816054
0.531170622
0.1965672612
0.1703263387
0.4980596387
0.2228081836
0.5642816054
0.531170622
0.1965672612
0.1739929612
0.5056556098
0.2274513444
0.5725516596
0.5391036347
0.2007221528
0.1739929612
0.5056556098
0.2274513444
0.5725516596
0.5391036347
0.2007221528
0.1845294271
0.5122076088
0.2412734287
0.579914945
0.5460612769
0.2129014279
0.1845294271
0.5122076088
0.2412734287
0.579914945
0.5460612769
0.2129014279
0.1895326821
0.5197419457
0.248204885
0.5886919018
0.5542169238
0.2188687835
0.1895326821
0.5197419457
0.248204885
0.5886919018
0.5542169238
0.2188687835
0.1983337216
0.5316544892
0.2611167485
0.6032399014
0.5674471953
0.229725235
0.1983337216
0.5316544892
0.2611167485
0.6032399014
0.5674471953
0.229725235
0.2126130447
0.5569345397
0.283348294
0.6352198972
0.5960772184
0.2479806694
0.2126130447
0.5569345397
0.283348294
0.6352198972
0.5960772184
0.2479806694
0.2169948371
0.5613088313
0.2909515911
0.6411011363
0.6012049838
0.2539732141
0.2169948371
0.5613088313
0.2909515911
0.6411011363
0.6012049838
0.2539732141
0.2169948371
0.5714607841
0.2909515911
0.6557172576
0.6135890208
0.2539732141
0.2169948371
0.5714607841
0.2909515911
0.6557172576
0.6135890208
0.2539732141
0.2169948371
0.5714607841
0.2909515911
0.6557172576
0.6135890208
0.2539732141
0.2169948371
0.5714607841
0.2909515911
0.6557172576
0.6135890208
0.2539732141
0.2169948371
0.578695656
0.2909515911
0.6717164011
0.6252060285
0.2539732141
0.2169948371
0.578695656
0.2909515911
0.6717164011
0.6252060285
0.2539732141
0.2169948371
0.578695656
0.2909515911
0.6717164011
0.6252060285
0.2539732141
0.2169948371
0.578695656
0.2909515911
0.6717164011
0.6252060285
0.2539732141
0.2169948371
0.5837136178
0.2909515911
0.7389820428
0.6613478303
0.2539732141
0.2169948371
0.5837136178
0.2909515911
0.7389820428
0.6613478303
0.2539732141
0.2169948371
0.5837136178
0.2909515911
0.7389820428
0.6613478303
0.2539732141
0.2169948371
0.5837136178
0.2909515911
0.7389820428
0.6613478303
0.2539732141
Fig 1f
55
55
55
66
66
77
77
88
88
99
99
1010
1010
1111
1111
1212
1212
1313
1313
1414
1414
1515
1515
1616
1616
1717
1717
1818
1818
1919
1919
2020
2020
2121
2121
2222
2222
2323
2323
2424
2424
2525
2525
2626
2626
2727
2727
2828
GRADE 1-5
GRADE 3-5
yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors for GRADE 1-5 and GRADE 3-5Wilms
0.1661849711
0.049132948
0.1661849711
0.049132948
0.1806358382
0.0520231214
0.1806358382
0.0520231214
0.2052023121
0.063583815
0.2052023121
0.063583815
0.225433526
0.0693641618
0.225433526
0.0693641618
0.2456647399
0.0823699422
0.2456647399
0.0823699422
0.2645234004
0.088187048
0.2645234004
0.088187048
0.2878267167
0.0984162409
0.2878267167
0.0984162409
0.3130017486
0.1102809433
0.3130017486
0.1102809433
0.3327248838
0.1178747605
0.3327248838
0.1178747605
0.3608731225
0.128828842
0.3608731225
0.128828842
0.3888421769
0.1470666216
0.3888421769
0.1470666216
0.4158112809
0.1506892187
0.4158112809
0.1506892187
0.4434211733
0.1586606614
0.4434211733
0.1586606614
0.461065746
0.1697798572
0.461065746
0.1697798572
0.4895516356
0.1777638043
0.4895516356
0.1777638043
0.5140236045
0.1873001856
0.5140236045
0.1873001856
0.5291921802
0.195271374
0.5291921802
0.195271374
0.5562561127
0.2002145461
0.5562561127
0.2002145461
0.5672821593
0.2121409294
0.5672821593
0.2121409294
0.5879559966
0.2204491965
0.5879559966
0.2204491965
0.5879559966
0.2204491965
0.5879559966
0.2204491965
0.5879559966
0.2204491965
0.5879559966
0.2204491965
0.5879559966
0.2204491965
0.5879559966
0.2204491965
0.5879559966
0.2204491965
0.5879559966
0.2204491965
Fig 1f-CI
555555
555555
555555
666666
666666
777777
777777
888888
888888
999999
999999
101010101010
101010101010
111111111111
111111111111
121212121212
121212121212
131313131313
131313131313
141414141414
141414141414
151515151515
151515151515
161616161616
161616161616
171717171717
171717171717
181818181818
181818181818
191919191919
191919191919
202020202020
202020202020
212121212121
212121212121
222222222222
222222222222
232323232323
232323232323
242424242424
242424242424
252525252525
252525252525
262626262626
262626262626
272727272727
272727272727
282828282828
GRADE 1-5
GRADE 3-5
Wilm-L
Wilm-L
Wilm-U
Wilm-U
yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors for GRADE 1-5 and GRADE 3-5Wilms
0.1661849711
0.049132948
0.0330283705
0.1384496143
0.0652375255
0.1939203278
0.1661849711
0.049132948
0.0330283705
0.1384496143
0.0652375255
0.1939203278
0.1806358382
0.0520231214
0.0354768517
0.1519713979
0.0685693911
0.2093002784
0.1806358382
0.0520231214
0.0354768517
0.1519713979
0.0685693911
0.2093002784
0.2052023121
0.063583815
0.0454031079
0.1751122942
0.0817645222
0.2352923301
0.2052023121
0.063583815
0.0454031079
0.1751122942
0.0817645222
0.2352923301
0.225433526
0.0693641618
0.0504337317
0.1942990455
0.088294592
0.2565680065
0.225433526
0.0693641618
0.0504337317
0.1942990455
0.088294592
0.2565680065
0.2456647399
0.0823699422
0.0618856378
0.2135904801
0.1028542466
0.2777389996
0.2456647399
0.0823699422
0.0618856378
0.2135904801
0.1028542466
0.2777389996
0.2645234004
0.088187048
0.0670542235
0.2316534749
0.1093198725
0.2973933258
0.2645234004
0.088187048
0.0670542235
0.2316534749
0.1093198725
0.2973933258
0.2878267167
0.0984162409
0.0762033536
0.2540731398
0.1206291281
0.3215802936
0.2878267167
0.0984162409
0.0762033536
0.2540731398
0.1206291281
0.3215802936
0.3130017486
0.1102809433
0.0868882124
0.2783847667
0.1336736742
0.3476187306
0.3130017486
0.1102809433
0.0868882124
0.2783847667
0.1336736742
0.3476187306
0.3327248838
0.1178747605
0.0937532744
0.2974805014
0.1419962467
0.3679692662
0.3327248838
0.1178747605
0.0937532744
0.2974805014
0.1419962467
0.3679692662
0.3608731225
0.128828842
0.1036789303
0.3247963512
0.1539787536
0.3969498939
0.3608731225
0.128828842
0.1036789303
0.3247963512
0.1539787536
0.3969498939
0.3888421769
0.1470666216
0.1202331104
0.3519758548
0.1739001328
0.425708499
0.3888421769
0.1470666216
0.1202331104
0.3519758548
0.1739001328
0.425708499
0.4158112809
0.1506892187
0.1235040688
0.378130763
0.1778743686
0.4534917988
0.4158112809
0.1506892187
0.1235040688
0.378130763
0.1778743686
0.4534917988
0.4434211733
0.1586606614
0.1306307927
0.4048472054
0.1866905302
0.4819951412
0.4434211733
0.1586606614
0.1306307927
0.4048472054
0.1866905302
0.4819951412
0.461065746
0.1697798572
0.140475191
0.4218265029
0.1990845235
0.500304989
0.461065746
0.1697798572
0.140475191
0.4218265029
0.1990845235
0.500304989
0.4895516356
0.1777638043
0.1473805318
0.4489414111
0.2081470769
0.5301618601
0.4895516356
0.1777638043
0.1473805318
0.4489414111
0.2081470769
0.5301618601
0.5140236045
0.1873001856
0.1554111913
0.4719778708
0.2191891799
0.5560693381
0.5140236045
0.1873001856
0.1554111913
0.4719778708
0.2191891799
0.5560693381
0.5291921802
0.195271374
0.161837352
0.4859203557
0.228705396
0.5724640047
0.5291921802
0.195271374
0.161837352
0.4859203557
0.228705396
0.5724640047
0.5562561127
0.2002145461
0.1656116008
0.5104022029
0.2348174914
0.6021100225
0.5562561127
0.2002145461
0.1656116008
0.5104022029
0.2348174914
0.6021100225
0.5672821593
0.2121409294
0.1743159976
0.520110394
0.2499658612
0.6144539245
0.5672821593
0.2121409294
0.1743159976
0.520110394
0.2499658612
0.6144539245
0.5879559966
0.2204491965
0.1796735679
0.5376284019
0.261224825
0.6382835913
0.5879559966
0.2204491965
0.1796735679
0.5376284019
0.261224825
0.6382835913
0.5879559966
0.2204491965
0.1796735679
0.5376284019
0.261224825
0.6382835913
0.5879559966
0.2204491965
0.1796735679
0.5376284019
0.261224825
0.6382835913
0.5879559966
0.2204491965
0.1796735679
0.5376284019
0.261224825
0.6382835913
0.5879559966
0.2204491965
0.1796735679
0.5376284019
0.261224825
0.6382835913
0.5879559966
0.2204491965
0.1796735679
0.5376284019
0.261224825
0.6382835913
0.5879559966
0.2204491965
0.1796735679
0.5376284019
0.261224825
0.6382835913
0.5879559966
0.2204491965
0.1796735679
0.5376284019
0.261224825
0.6382835913
0.5879559966
0.2204491965
0.1796735679
0.5376284019
0.261224825
0.6382835913
Fig 1g
55
55
55
66
66
77
77
88
88
99
99
1010
1010
1111
1111
1212
1212
1313
1313
1414
1414
1515
1515
1616
1616
1717
1717
1818
1818
1919
1919
2020
2020
2121
2121
2222
2222
2323
2323
2424
2424
2525
2525
2626
2626
2727
2727
2828
GRADE 1-5
GRADE 3-5
yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors GRADE 1-5 and GRADE 3-5Neuroblastoma
0.2528735632
0.0804597701
0.2528735632
0.0804597701
0.2644035125
0.0873911529
0.2644035125
0.0873911529
0.2851574213
0.0897016138
0.2851574213
0.0897016138
0.30591133
0.0966329966
0.30591133
0.0966329966
0.3174412794
0.1012658589
0.3174412794
0.1012658589
0.3335832084
0.1082151522
0.3335832084
0.1082151522
0.3520311273
0.1151644455
0.3520311273
0.1151644455
0.3660697909
0.1198468571
0.3660697909
0.1198468571
0.3988266725
0.1339702286
0.3988266725
0.1339702286
0.4105723543
0.1410909256
0.4105723543
0.1410909256
0.4318015867
0.1506661053
0.4318015867
0.1506661053
0.44639277
0.1605842765
0.44639277
0.1605842765
0.4740223972
0.170973247
0.4740223972
0.170973247
0.4927212359
0.1796276305
0.4927212359
0.1796276305
0.5170297261
0.1896162314
0.5170297261
0.1896162314
0.5279398359
0.1934654971
0.5279398359
0.1934654971
0.5442215899
0.2072681895
0.5442215899
0.2072681895
0.5590496159
0.2239336626
0.5590496159
0.2239336626
0.571645466
0.2239336626
0.571645466
0.2239336626
0.5974097047
0.2343999017
0.5974097047
0.2343999017
0.6130243949
0.2544352738
0.6130243949
0.2544352738
0.6353310951
0.2859194299
0.6353310951
0.2859194299
0.6353310951
0.3357693438
0.6353310951
0.3357693438
0.6353310951
0.3357693438
0.6353310951
0.3357693438
Fig 1g- CI
555555
555555
555555
666666
666666
777777
777777
888888
888888
999999
999999
101010101010
101010101010
111111111111
111111111111
121212121212
121212121212
131313131313
131313131313
141414141414
141414141414
151515151515
151515151515
161616161616
161616161616
171717171717
171717171717
181818181818
181818181818
191919191919
191919191919
202020202020
202020202020
212121212121
212121212121
222222222222
222222222222
232323232323
232323232323
242424242424
242424242424
252525252525
252525252525
262626262626
262626262626
272727272727
272727272727
282828282828
GRADE 1-5
GRADE 3-5
Neuro-L
Neuro-L
Neuro-U
Neuro-U
yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors GRADE 1-5 and GRADE 3-5Neuroblastoma
0.2528735632
0.0804597701
0.0548982779
0.2120265591
0.1060212624
0.2937205673
0.2528735632
0.0804597701
0.0548982779
0.2120265591
0.1060212624
0.2937205673
0.2644035125
0.0873911529
0.0608461923
0.2229554504
0.1139361136
0.3058515746
0.2644035125
0.0873911529
0.0608461923
0.2229554504
0.1139361136
0.3058515746
0.2851574213
0.0897016138
0.0628403591
0.2427188138
0.1165628686
0.3275960288
0.2851574213
0.0897016138
0.0628403591
0.2427188138
0.1165628686
0.3275960288
0.30591133
0.0966329966
0.0688546891
0.2625928645
0.1244113042
0.3492297956
0.30591133
0.0966329966
0.0688546891
0.2625928645
0.1244113042
0.3492297956
0.3174412794
0.1012658589
0.0728976451
0.2736793399
0.1296340726
0.3612032188
0.3174412794
0.1012658589
0.0728976451
0.2736793399
0.1296340726
0.3612032188
0.3335832084
0.1082151522
0.0789966558
0.289252506
0.1374336486
0.3779139108
0.3335832084
0.1082151522
0.0789966558
0.289252506
0.1374336486
0.3779139108
0.3520311273
0.1151644455
0.0851340382
0.3071221772
0.1451948529
0.3969400773
0.3520311273
0.1151644455
0.0851340382
0.3071221772
0.1451948529
0.3969400773
0.3660697909
0.1198468571
0.0892822294
0.3207506949
0.1504114848
0.4113888868
0.3660697909
0.1198468571
0.0892822294
0.3207506949
0.1504114848
0.4113888868
0.3988266725
0.1339702286
0.1018747581
0.3527152423
0.166065699
0.4449381027
0.3988266725
0.1339702286
0.1018747581
0.3527152423
0.166065699
0.4449381027
0.4105723543
0.1410909256
0.1082634542
0.3642267796
0.1739183969
0.456917929
0.4105723543
0.1410909256
0.1082634542
0.3642267796
0.1739183969
0.456917929
0.4318015867
0.1506661053
0.1168900899
0.385096066
0.1844421206
0.4785071074
0.4318015867
0.1506661053
0.1168900899
0.385096066
0.1844421206
0.4785071074
0.44639277
0.1605842765
0.1258323259
0.3994501923
0.1953362271
0.4933353477
0.44639277
0.1605842765
0.1258323259
0.3994501923
0.1953362271
0.4933353477
0.4740223972
0.170973247
0.1351912108
0.4266688025
0.2067552832
0.521375992
0.4740223972
0.170973247
0.1351912108
0.4266688025
0.2067552832
0.521375992
0.4927212359
0.1796276305
0.1429035777
0.4450691939
0.2163516832
0.5403732778
0.4927212359
0.1796276305
0.1429035777
0.4450691939
0.2163516832
0.5403732778
0.5170297261
0.1896162314
0.1516401031
0.4687788782
0.2275923596
0.565280574
0.5170297261
0.1896162314
0.1516401031
0.4687788782
0.2275923596
0.565280574
0.5279398359
0.1934654971
0.1549278834
0.4792277853
0.2320031108
0.5766518865
0.5279398359
0.1934654971
0.1549278834
0.4792277853
0.2320031108
0.5766518865
0.5442215899
0.2072681895
0.1663488749
0.494651861
0.2481875041
0.5937913189
0.5442215899
0.2072681895
0.1663488749
0.494651861
0.2481875041
0.5937913189
0.5590496159
0.2239336626
0.17974667
0.5083429309
0.2681206552
0.6097563009
0.5590496159
0.2239336626
0.17974667
0.5083429309
0.2681206552
0.6097563009
0.571645466
0.2239336626
0.17974667
0.5194851293
0.2681206552
0.6238058027
0.571645466
0.2239336626
0.17974667
0.5194851293
0.2681206552
0.6238058027
0.5974097047
0.2343999017
0.1862886933
0.5408962867
0.2825111102
0.6539231228
0.5974097047
0.2343999017
0.1862886933
0.5408962867
0.2825111102
0.6539231228
0.6130243949
0.2544352738
0.1936704096
0.5510647983
0.315200138
0.6749839915
0.6130243949
0.2544352738
0.1936704096
0.5510647983
0.315200138
0.6749839915
0.6353310951
0.2859194299
0.2022033184
0.5634325029
0.3696355414
0.7072296873
0.6353310951
0.2859194299
0.2022033184
0.5634325029
0.3696355414
0.7072296873
0.6353310951
0.3357693438
0.2141392298
0.5634325029
0.4573994577
0.7072296873
0.6353310951
0.3357693438
0.2141392298
0.5634325029
0.4573994577
0.7072296873
0.6353310951
0.3357693438
0.2141392298
0.5634325029
0.4573994577
0.7072296873
0.6353310951
0.3357693438
0.2141392298
0.5634325029
0.4573994577
0.7072296873
Fig 1h
55
55
55
66
66
77
77
88
88
99
99
1010
1010
1111
1111
1212
1212
1313
1313
1414
1414
1515
1515
1616
1616
1717
1717
1818
1818
1919
1919
2020
2020
2121
2121
2222
2222
2323
2323
2424
2424
2525
2525
2626
2626
2727
2727
2828
GRADE 1-5
GRADE 3-5
yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors for GRADE 1-5 and GRADE 3-5Sarcoma
0.3933209647
0.1781076067
0.3933209647
0.1781076067
0.4109733542
0.1827669564
0.4109733542
0.1827669564
0.4240430121
0.1893202107
0.4240430121
0.1893202107
0.4438119662
0.195927881
0.4438119662
0.195927881
0.4646318775
0.2092232177
0.4646318775
0.2092232177
0.4830596523
0.2170747753
0.4830596523
0.2170747753
0.4991959009
0.2304119077
0.4991959009
0.2304119077
0.5095297933
0.2368198598
0.5095297933
0.2368198598
0.5203653309
0.2468959153
0.5203653309
0.2468959153
0.5294671825
0.2516455711
0.5294671825
0.2516455711
0.537962244
0.2568093898
0.537962244
0.2568093898
0.5457322592
0.2680011765
0.5457322592
0.2680011765
0.5571395017
0.2772846862
0.5571395017
0.2772846862
0.5811901793
0.2826386008
0.5811901793
0.2826386008
0.5978465528
0.2909784633
0.5978465528
0.2909784633
0.6144671062
0.2958084995
0.6144671062
0.2958084995
0.6218748324
0.3075385874
0.6218748324
0.3075385874
0.628208975
0.3184688966
0.628208975
0.3184688966
0.6425891907
0.3312894097
0.6425891907
0.3312894097
0.660767954
0.3312894097
0.660767954
0.3312894097
0.6676582917
0.3398549473
0.6676582917
0.3398549473
0.6781751229
0.3398549473
0.6781751229
0.3398549473
0.6781751229
0.3398549473
0.6781751229
0.3398549473
0.7160357153
0.3398549473
0.7160357153
0.3398549473
Fig 1h CI
555555
555555
555555
666666
666666
777777
777777
888888
888888
999999
999999
101010101010
101010101010
111111111111
111111111111
121212121212
121212121212
131313131313
131313131313
141414141414
141414141414
151515151515
151515151515
161616161616
161616161616
171717171717
171717171717
181818181818
181818181818
191919191919
191919191919
202020202020
202020202020
212121212121
212121212121
222222222222
222222222222
232323232323
232323232323
242424242424
242424242424
252525252525
252525252525
262626262626
262626262626
272727272727
272727272727
282828282828
GRADE 1-5
Sar_L
Sar-U
GRADE 3-5
Sar-L
Sar_U
yrs since diagnosis
cumulative incidence
Cumulative incidence curves of physical health conditions in survivors for GRADE 1-5 and GRADE 3-5Sarcoma
0.3933209647
0.3641601447
0.4224817848
0.1781076067
0.1552676432
0.2009475702
0.3933209647
0.3641601447
0.4224817848
0.1781076067
0.1552676432
0.2009475702
0.4109733542
0.3816005996
0.4403461088
0.1827669564
0.1596942164
0.2058396965
0.4109733542
0.3816005996
0.4403461088
0.1827669564
0.1596942164
0.2058396965
0.4240430121
0.3945349031
0.4535511211
0.1893202107
0.1659273234
0.212713098
0.4240430121
0.3945349031
0.4535511211
0.1893202107
0.1659273234
0.212713098
0.4438119662
0.4141300066
0.4734939258
0.195927881
0.1722190466
0.2196367154
0.4438119662
0.4141300066
0.4734939258
0.195927881
0.1722190466
0.2196367154
0.4646318775
0.4348132681
0.494450487
0.2092232177
0.1849050022
0.2335414333
0.4646318775
0.4348132681
0.494450487
0.2092232177
0.1849050022
0.2335414333
0.4830596523
0.4531384081
0.5129808966
0.2170747753
0.1923968811
0.2417526695
0.4830596523
0.4531384081
0.5129808966
0.2170747753
0.1923968811
0.2417526695
0.4991959009
0.4691824707
0.5292093311
0.2304119077
0.2051119032
0.2557119121
0.4991959009
0.4691824707
0.5292093311
0.2304119077
0.2051119032
0.2557119121
0.5095297933
0.4794604273
0.5395991592
0.2368198598
0.2112163185
0.262423401
0.5095297933
0.4794604273
0.5395991592
0.2368198598
0.2112163185
0.262423401
0.5203653309
0.4902203118
0.55051035
0.2468959153
0.2207981293
0.2729937012
0.5203653309
0.4902203118
0.55051035
0.2468959153
0.2207981293
0.2729937012
0.5294671825
0.4992425399
0.5596918252
0.2516455711
0.225300769
0.2779903731
0.5294671825
0.4992425399
0.5596918252
0.2516455711
0.225300769
0.2779903731
0.537962244
0.5076365386
0.5682879495
0.2568093898
0.2301650854
0.2834536942
0.537962244
0.5076365386
0.5682879495
0.2568093898
0.2301650854
0.2834536942
0.5457322592
0.5152876911
0.5761768273
0.2680011765
0.2406538231
0.2953485299
0.5457322592
0.5152876911
0.5761768273
0.2680011765
0.2406538231
0.2953485299
0.5571395017
0.5264545392
0.5878244643
0.2772846862
0.2492950558
0.3052743167
0.5571395017
0.5264545392
0.5878244643
0.2772846862
0.2492950558
0.3052743167
0.5811901793
0.5498686921
0.6125116665
0.2826386008
0.2542094889
0.3110677126
0.5811901793
0.5498686921
0.6125116665
0.2826386008
0.2542094889
0.3110677126
0.5978465528
0.5659600417
0.629733064
0.2909784633
0.2617315541
0.3202253724
0.5978465528
0.5659600417
0.629733064
0.2909784633
0.2617315541
0.3202253724
0.6144671062
0.5819223986
0.6470118138
0.2958084995
0.2660069823
0.3256100167
0.6144671062
0.5819223986
0.6470118138
0.2958084995
0.2660069823
0.3256100167
0.6218748324
0.5889171681
0.6548324966
0.3075385874
0.2761033349
0.3389738399
0.6218748324
0.5889171681
0.6548324966
0.3075385874
0.2761033349
0.3389738399
0.628208975
0.5946801562
0.6617377938
0.3184688966
0.2851988872
0.3517389061
0.628208975
0.5946801562
0.6617377938
0.3184688966
0.2851988872
0.3517389061
0.6425891907
0.6076038843
0.6775744972
0.3312894097
0.2956467047
0.3669321147
0.6425891907
0.6076038843
0.6775744972
0.3312894097
0.2956467047
0.3669321147
0.660767954
0.6234809874
0.6980549206
0.3312894097
0.2956467047
0.3669321147
0.660767954
0.6234809874
0.6980549206
0.3312894097
0.2956467047
0.3669321147
0.6676582917
0.6288681406
0.7064484428
0.3398549473
0.3009424447
0.3787674499
0.6676582917
0.6288681406
0.7064484428
0.3398549473
0.3009424447
0.3787674499
0.6781751229
0.6357369397
0.7206133062
0.3398549473
0.3009424447
0.3787674499
0.6781751229
0.6357369397
0.7206133062
0.3398549473
0.3009424447
0.3787674499
0.6781751229
0.6357369397
0.7206133062
0.3398549473
0.30