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Friday, September 14, 2018 3:15PM-4:15PM
COG Track at APHON
Beyond the Cure: The COG’s Efforts to Improve Outcomes for Pediatric Cancer Survivors Long after Treatment has Finished Eleanor Hendershot, MN, BScN, RN(EC) Nurse Practitioner COG Educational Track at APHON 2018 1
C223_Beyond The Cure: Late Effects and COG
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COG Track at APHON
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Disclosure Eleanor Hendershot has no industry relationships. Off label use will not be discussed.
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COG Track at APHON
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COG Disclosure The information in this presentation is intended for educational purposes only and is solely for the use of the individual nurse learner. This information is not intended as the sole source of guidance in providing Children’s Oncology Group (COG) protocol-directed nursing care, and current COG protocols should always be consulted prior to making patient care decisions for any patient enrolled on a COG protocol. Learners should also be aware that COG protocols are research plans designed to investigate particular study questions, that recommendations for treatment and dosing are made within the context of specific research aims, and that these recommendations are intended only for use within a structured research setting. Although every attempt has been made to assure that the informational content contained herein is as accurate and complete as possible as of the date of presentation, no warranty or representation, express or implied, is made as to the accuracy, reliability, completeness, relevance, or timeliness of this content. This information may not be copied or redistributed in any form, or used for any purpose other than nursing education.
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Friday, September 14, 2018 3:15PM-4:15PM
COG Track at APHON
Ann – 58 year old woman Initially diagnosed with Wilms tumor at age 5 yrs in 1965! Treatment Left nephrectomy – chemo hx unknown Radiation 2500 cGy to whole abd Right kidney shielded – received total dose of 1500 cGy Relapse Treatment
Pulmonary 2000 cGy to thorax
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COG Track at APHON
Ann’s Late Effects Now Cardiovascular
Endocrinopathies
SMN
MI Cardiomyopathy Abnormal heart function Sinus tachycardia with 1st degree heart block • Hyperlipidemia • • • •
• • • •
POF age 16 yrs Hypothyroidism Hypercalcemia Basal cell carcinomas (on back and abd in XRT field)
Renal
• Hypertension - age 18 yrs • CRF - age 19 yrs -now grade 4 -creatinine of 4.48 • Anemia -most likely due to CRF
Musculoskeletal • Osteoporosis
GYN
• Cervical dysplasia -secondary to XRT 5
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COG Track at APHON
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Presentation Objectives 1. Describe what late effects are and the magnitude of their existence a) b)
Identify commonly occurring late effects. Highlight the new LTFU Guidelines through the COG
2. Use survivor-specific exemplars to examine treatment-related exposures and potential late effects. 3. Identify late effects protocols open in the COG and highlight ALTE15N2 ‘Late effects after high risk neuroblastoma’
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COG Track at APHON
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What are late effects?
“a broad range of persistent adverse effects that are related to the disease process, its therapy or a combination of the two”
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What Causes Late Effects? Treatment
Treatment Events
Tumor
Late Effects Pre Cancer conditions
Genetic factors
Host Factors
Health Behaviors 8
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COG Track at APHON
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Background
> 80% of children with cancer now survive into adulthood
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© SEER Annual report to the nation, 2017
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Reprinted with permission from Brian Carey
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What is the Cost of Cure? Findings from the Childhood Cancer Survivor Study (CCSS) By 30 years post cancer: • •
73%: ≥1 chronic health condition 42%: severe/life threatening condition
8.2 times more likely to have a severe/life threatening health condition than their siblings Mortality rate is 8.4 times higher than age-and sex-matched general population
Oeffinger, NEJM, 2006; Armstrong, JCO, 2009
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Late Effects Occurring in the St Jude Lifetime Cohort
Courtesy of Melissa Hudson, used with permission.
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Risk-Based Screening
Courtesy of Melissa Hudson, used with permission.
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C223_Beyond The Cure: Late Effects and COG
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Examples of Systems Being Impacted by Late Effects Neurocognitive
Cardiac
Endocrine Renal/Urinary
Hepatic Musculoskeletal
Sensory Neurologic Second Malignancies
Pulmonary Immune Reproductive
Skeletal Gastrointestinal
Psychosocial 15
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Neurocognitive Effects Risks increased with surgery, radiation & MTX = BT and ALL Prevalence of Cognitive Impairment in ALL vs. BT ALL (% impairment)
BT (% impairment)
No CRT
18 Gy
24 Gy
No CRT
Focal RT
CSRT
Intelligence
9.3
12
27
9.8
14.3
32.5
Academics
6.1
9.2
15.4
9.8
23.5
44.7
Attention
14.5
21.5
31.1
27.9
41.2
47.5
Memory
13.1
18.7
30.6
17.7
36.6
54.9
Processing Speed
16.8
16.9
27
40
64.6
66.3
Executive Function
15.9
23
31.7
37.1
52.1
68.3
Krull et al., 2018 (data from the St Jude Lifetime cohort)
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Endocrinopathies (CCSS) Risks increased with radiation, alkylating agents Incidence of endocrinopathies ♦ ♦ ♦
44% had at least 1 16.7% had 2 6.6% had 3 or more
Incidence based on cancer type: ♦ ♦ ♦ ♦
HL (60%) Leukemia (46%) NHL (40%) Wilms (29%)
- CNS tumor (54%) - Sarcomas (41%) - NBL (32%) - Bone (28%) Mostoufi-Moab et al., 2016
C223_Beyond The Cure: Late Effects and COG
Illustration © Children’s Oncology Group 2013, used with permission
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Endocrinopathies with Cranial Radiation Endocrine Diagnosis
At What Dose
Example of Tumours
Growth Hormone Deficiency
> 18 Gy
BT, ALL
Obesity/Metabolic Syndrome
> 18 Gy
BT,ALL
Precocious Puberty
> 18 Gy > 40 Gy > 40 Gy
BT, ALL BT BT
> 40 Gy > 40 Gy
BT BT
Delayed Puberty Central Hypothyroidism Central Adrenal Insufficiency Hyperprolactinemia
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Friday, September 14, 2018 3:15PM-4:15PM
COG Track at APHON
Cardiac Late Effects Increased risks with anthracyclines & XRT to mediastinum Compared with siblings, survivors have a: ♦
5-fold increase of • Myocardial infarction • Valvar abnormalities
♦
6-fold increased risk • For heart failure • Pericardial disease
♦
Survivors > 35 years have an almost 11-fold increased risk for HF
Anthracycline exposure risks ♦
~65% will have some kind of late cardiovascular abnormality. Franco & Lipshultz, 2015; Harake, Franco, et al, 2013 Illustration © Children’s Oncology Group 2013, used with permission
Risks are persistent and progressive over the years.
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Fertility Late Effects – findings from CCSS Before the age of 30, pregnancy and live birth rates are not significantly different between patients who ultimately develop POF and those who do not Risk factors ♦ ♦ ♦ ♦
> 15 years at time of diagnosis HSCT HL diagnosis Alkylating agents • Procarbazine dose > 4000 mg/m2 • CPM equivalent dose of > 6000 mg/m2 (including procarbazine)
♦
Any radiation therapy delivered to the gonads Illustration by Aimee Ermel, 2013
Levine et al., 2018
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SMN Risk – Findings from CCSS Risk increased with radiotherapy, alkylating agents, and epipodophyllotoxins Years from Treatment
Incidence
Type of Tumours
(compared to general population)
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3.2% (6-fold increase)
All types
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7.9%
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4-fold increase
Bone, CNS, thyroid, head & neck, breast Breast, kidney, thyroid, STS Turcotte et al., 2018
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SMN Risk – Findings from CCSS
©2009 by American Society of Clinical Oncology
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Meadows, et al, 2009
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COG Long Term Follow-up Guidelines
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Long Term Follow Up Guidelines
Simplified design Radiation fields re-defined Radiation dose cut-offs largely eliminated
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How to use them
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COG Track at APHON
Nick (9) Hx: HR NBL Alex (33) Hx: Osteo
Sarah (22) Hx: Ewing’s
The Survivors Vanessa (13) Hx: MBL
Jasmine (30) Hx: HL
Cody (19) HX: ALL
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COG Track at APHON
Friday, September 14, 2018 3:15PM-4:15PM
Jasmine (30 yrs old) History of Hodgkin’s Lymphoma Stage 2 B (bulk) at age 16 yrs Treatment Chemotherapy ♦ ♦ ♦ ♦ ♦ ♦
DOXO 250 mg/m2 BLEO VBL ETOP PRED CPM 3200 mg/m2
Radiation Therapy ♦
Modified mantle • 150 cGy fractions x 14 = 2100 cGy in 14 fractions 27
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Friday, September 14, 2018 3:15PM-4:15PM
COG Track at APHON
Jasmine’s Potential LE Risks Eye
Cataracts
SMN
Skin Breast Thyroid
Cardiac
Cardiomyopathy Valve disease
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Friday, September 14, 2018 3:15PM-4:15PM
COG Track at APHON
Jasmine’s Potential LE Risks Pulmonary
Pulmonary fibrosis
Endocrinopathies
Thyroid dysfunction Infertility/POF
Musculoskeletal (↓BMD)
AVN Scoliosis/Kyphosis Osteopenia/Osteoporosis
Eligible for ALTE1621
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COG Track at APHON
Friday, September 14, 2018 3:15PM-4:15PM
ALTE1621: Pharmacologic reversal of ventricular remodeling in childhood cancer survivors at risk for heart failure (PREVENT-HF): A phase 2b randomized placebo-controlled (Carvedilol) trial. Objectives To study a physiologically plausible pharmacological risk-reduction strategy for childhood cancer survivors at high risk for developing anthracycline-related heart failure by testing the impact of a two-year course of low-dose carvedilol on: ♦
Surrogate echocardiographic indices of heart failure risk • Including both new and established measures
♦
Biomarkers associated with myocardial injury and heart failure risk
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COG Track at APHON
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Long Term Follow up Guidelines
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More Chemotherapy Late Effects
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COG Track at APHON
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Radiation Late Effects
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COG Track at APHON
Friday, September 14, 2018 3:15PM-4:15PM
Vanessa (13 yrs old) History of medulloblastoma at age 9 yrs Treatment per A9961 Surgery (PF) Chemotherapy ♦ ♦ ♦
VCR CDDP CPM 16 gm/m2
Radiation Therapy ♦
CSRT • 2340 cGy to whole brain and spine • 3240 cGy to tumor bed
Investigations IGF: 44 (89-488) TSH: 5.38 (0.7-4.27) T4: 8.4 (11.4-17.6) Cortisol Low 34
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Friday, September 14, 2018 3:15PM-4:15PM
COG Track at APHON
Vanessa’s LE’s Late Effect
Intervention
ACTH deficiency
Hydrocortisone
GH deficiency
GH injections
Hypothyroidism
Levothyroxine
Eligible for ALTE05N1
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COG Track at APHON
Friday, September 14, 2018 3:15PM-4:15PM
ALTE05N1: Umbrella Long-Term Follow-Up Protocol
Objectives To keep in contact with participants of COG clinical trials so that up-to-date contact information is available on these participants as they get older. To facilitate timely and efficient collection of off-therapy, protocol-driven data by member institutions in order to enhance the scope and quality of COG health-related outcomes research.
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Friday, September 14, 2018 3:15PM-4:15PM
COG Track at APHON
Nick (9 yrs old) History of HR NBL at age 3 yrs Treatment per ANBL0531 Chemotherapy ♦ ♦ ♦ ♦ ♦
DOXO 120 mg/m2 CPM 5 gm/m2 VCR/TOPO ETOP/CDDP MELPH
Surgery (including nephrectomy) Radiation Therapy ♦
Flank - 1000 cGy
Immunotherapy ♦
CH 14.18 + Il2/GMCSF
Relapse at age 4 yrs ♦
Large frontal lobe intracranial mass • Mass effect • Midline shift with edema
Relapse Treatment Surgery with gross total resection Radiation Therapy ♦
Cranial spinal radiation therapy • With a frontal lobe boost of 1260 cGy
Chemotherapy + Immunotherapy ♦
3F8 under experimental protocol 37
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Friday, September 14, 2018 3:15PM-4:15PM
COG Track at APHON
Nick’s LE’s System
LE
Endocrine
• GH deficiency
Renal
• Single kidney • Hypertension
Pulmonary
• Pulmonary fibrosis
CNS
• Hearing loss • Pupillary irregularity • Neurocognitively OK (for now) Eligible for ALTE15N2 38
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Friday, September 14, 2018 3:15PM-4:15PM
COG Track at APHON
ALTE15N2 (LEAHRN) Objectives To estimate the prevalence of late effects in high risk neuroblastoma survivors treated with contemporary therapy ♦ To identify demographic, clinical and treatment-related risk factors associated with the late effects ♦ To determine the impact of late effects on quality of life
To biobank blood specimens for future research
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COG Track at APHON
ALTE15N2 LEAHRN Schema Eligible pts recruited by site Eligible pts identified: -diagnosed AFTER 1/1/2000 -enrolled on ANBL00B1 with HR-NBL -survived at least 5 yrs from diagnosis -no cytotoxic anti-NBL therapy within 2 yrs of enrollment
Consent and enrollment onto ALTE15N2
Study procedures include: -clinical/laboratory studies (including biobanking) -provider hx and medical assessments -patient/parent completed forms -QOL measurements -medical record abstraction
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ALTE15N2: Data to be collected Lab Tests
Blood • Gonadal function (FSH, LH, estradiol, testosterone, AMH for females > 12 yrs) • Endocrine (HgA1C, IGF-1, TSH/T4) • Renal (BUN/Creat, cystatin C, GFR, Ca, Mag, PO4) Biospecimens for future studies • Plasma • DNA
Diagnostic Tests
Bone age if < 12 yrs ECHO PFT if > 8 yrs AUDIO Panorax dental x-ray 41
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Friday, September 14, 2018 3:15PM-4:15PM
COG Track at APHON
ALTE15N2: Data to be collected (cont..)
Questionnaires
Medical hx forms (adapted from St. Jude Lifetime Study) BRIEF (executive functioning) BASC-2 (behavior - social and emotional) PedsQL (QOL both general and cancer related) Body image questions Health behaviors
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Friday, September 14, 2018 3:15PM-4:15PM
COG Track at APHON
Sarah (22 yrs old) History of pelvic Ewing sarcoma at age 10 yrs Treatment per COG 7942 (POG 9354) Current symptoms Surgery Hot flashes Chemotherapy ♦ ♦ ♦ ♦ ♦
VCR 13.5 mg/m2 CPM 10.8 gm/m2 IFOS 72 gm/m2 ETOP 4 gm/m2 DOXO 375 mg/m2
(CED=28,800 mg/m2)
Radiation Therapy ♦
Pelvic
• 5400 cGy
Mood swings Irregular periods Scaling, bleeding skin lesion on upper right iliac crest
Investigations FSH: 134.6 (high) LH: 54.7 (high) Estradiol: <30 (low) Biopsy of skin lesion 43
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Friday, September 14, 2018 3:15PM-4:15PM
COG Track at APHON
Sarah’s LE’s System
LE
Intervention
Endocrine
• POF
SMN
• Basal cell carcinoma
• • • •
Started OCP to regulate cycle Oocyte cryopreservation not an option Surgical removal Annual dermatology screening
Eligible for ALTE1621 and ALTE03N1
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COG Track at APHON
Friday, September 14, 2018 3:15PM-4:15PM
ALTE1621: Pharmacologic reversal of ventricular remodeling in childhood cancer survivors at risk for heart failure (PREVENT-HF): A phase 2b randomized placebo-controlled (Carvedilol) trial. Objectives To determine the impact of a two-year course of low-dose carvedilol on surrogate echocardiographic indices of heart failure (HF) risk, including: ♦ ♦ ♦
Left Ventricular (LV) Posterior Wall Thickness-Dimension Ratio (LV T-D) a well-established index of early myocardial remodeling and subsequent HF risk (primary endpoint). LV systolic and diastolic function, and afterload – established echocardiographic indices associated with HF risk. Natriuretic peptides, troponins, and Galectin-3 - circulating biomarkers associated with myocardial injury, and HF risk.
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COG Track at APHON
Friday, September 14, 2018 3:15PM-4:15PM
ALTE03N1: Key Adverse Events after Childhood Cancer Objectives: To identify key adverse events (e.g., SMN, CHF) developing in patients who had a primary cancer diagnosed at age 21 or younger To determine associations between the key adverse events, the therapy given for the primary cancer, and characteristics of the survivors (such as genetic predisposition) To use this information to identify patients who are more likely to develop key adverse events, so that in the future they can be monitored more closely to detect the complications early, or when possible, to intervene and prevent these complications from occurring at all 46
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COG Track at APHON
Cody (19 yrs old) History of ALL at age 15 yrs Treatment Chemotherapy (included) ♦ ♦
DEX MTX
Radiation Therapy ♦
CRT • 1800 cGy to whole brain
Post treatment history ♦ ♦
Social isolation Obesity
C223_Beyond The Cure: Late Effects and COG
Investigations Cholesterol: Triglycerides TSH: T4: BMI BMD z score
288 (<200) 328 (<150) 5.7 (0.7-4.27) 9.7 (11.4-17.6) 35.1 (18.5-24.9) -2.2 (0 or higher+)
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Cody’s LE’s LE
Intervention
Hypothyroidism
• Levothyroxine
Hyperlipidemia
• Lifestyle changes • Exercise & Nutrition
(at risk for coronary artery disease)
Obesity
• Referral to Exercise Medicine Clinic • Exercise & Nutrition • Lifestyle changes
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Friday, September 14, 2018 3:15PM-4:15PM
COG Track at APHON
Cody’s LE’s (cont.) LE
Intervention
Osteoporosis
• Ca + Vit D • Fosomax • Weight bearing exercise
Emotional Issues
• Referral to psychology • Encourage participation in AYA groups (e.g., Stupid Cancer)
Eligible for ALTE1631 and ALTE07C1 49
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COG Track at APHON
Friday, September 14, 2018 3:15PM-4:15PM
ALTE1631: A Randomized Web-based Physical Activity Intervention among Children and Adolescents with Acute Lymphoblastic Leukemia Objectives To compare the effects of a web-based physical activity intervention on fitness of children and adolescents following treatment for ALL, and determine the effects of: ♦ ♦
The web-based intervention alone versus The web-based intervention plus: • Rewards and • Structured social interaction between participants
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COG Track at APHON
Friday, September 14, 2018 3:15PM-4:15PM
ALTE07C1: Neuropsychological, Social, Emotional, and Behavioral Outcomes in Children with Cancer Objectives To use a standardized battery of age-appropriate neuropsychological and behavioral tests in conjunction with COG Phase II and Phase III clinical trials in order to evaluate cognitive, social, emotional, and behavioral functioning over time.
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COG Track at APHON
Alex (33 yrs old) History of osteosarcoma at age 14 yrs Treatment on P9754 Chemotherapy ♦ ♦ ♦ ♦
MTX CDDP IFOS 36 G/m2 DOXO 450 mg/m2 with DRZ
Post treatment history ♦ ♦ ♦
Lost to F/U for 3 yrs Presents to clinic with fatigue/malaise Has questions re: fertility
Investigations ECHO:
EF 30% (50-70%)
Sperm count:
15 mil (20-150 mil) 12% motility (>50%) 52
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Friday, September 14, 2018 3:15PM-4:15PM
COG Track at APHON
Alex’s LE’s LE
Intervention
Cardiomyopathy
• Ramipril
Reduced sperm count
• Fertility Services as needed
Eligible for ALTE11C2 and ALTE16C1 53
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COG Track at APHON
Friday, September 14, 2018 3:15PM-4:15PM
AL11C2: Health Effects After Anthracycline and Radiation (HEART): Dexrazoxane (DRZ) and Prevention of Anthracycline-Related Cardiomyopathy Objectives To determine if patients treated on legacy POG or DFCI protocols who received cardioprotection with DRZ during anthracycline chemotherapy have decreased markers of CHF compared with patients who received the same or similar anthracycline treatment but did not receive DRZ Eligible patients include: ♦ Patients with leukemia and lymphoma treated on P9404, P9425, P9426, and DFCI 95-01 ♦ Patients with osteosarcoma treated on P9754 54
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COG Track at APHON
Friday, September 14, 2018 3:15PM-4:15PM
ALTE16C1: Effects of modern chemotherapy regimens on spermatogenesis and steroidogenesis in adolescent and young adult survivors of osteosarcoma Objectives To determine whether there are differences in the rates of infertility and/or the expression of biomarkers of spermatogenesis and steroidogenesis in male osteosarcoma survivors who were treated with cisplatin (with or without ifosfamide), compared to male controls without a history of cancer. To evaluate whether therapy with cisplatin (with or without ifosfamide) for the treatment of osteosarcoma alters sperm DNA methylation.
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COG Track at APHON
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Current COG Late Effects Studies
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COG Track at APHON
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Open Late Effects Studies in COG Protocol ALTE03N1 ALTE05N1 ALTE07C1
Title Key Adverse Events after Childhood Cancer Umbrella Long-term Follow-up Protocol Neuropsychological, Social, Emotional and Behavioral Outcomes in Children with Cancer ALTE11C2 Health Effects after Anthracycline and Radiation Therapy (HEART): Dexrazoxane and Prevention of Anthracyclinerelated Cardiomyopathy
Opened 2004 2008 2008 2013
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COG Track at APHON
Open Late Effects Studies in COG (cont.) Protocol
Title
ALTE15N2 LEAHRN (Late Effects After High-Risk Neuroblastoma) Study ALTE1621 Pharmacologic Reversal of Ventricular Remodeling in Childhood Cancer Survivors at Risk for Heart Failure (PREVENT-HF): A Phase 2b Randomized Placebo-Controlled (Carvedilol) Trial ALTE1631 A Randomized Web-based Physical Activity Intervention among Children and Adolescents with ALL ALTE16C1 Effects of Modern Chemotherapy Regimens on Spermatogenesis and Steroidogenesis in AYA Survivors of Osteosarcoma
Opened 2017 2016
2017 2017
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Take Home Points Cure is not the end, but a new beginning Late effects occur commonly ♦ ♦
Surveillance leads to early detection and prompt treatment Use the follow up guidelines to ensure that your patients are being screened appropriately
Be aware of open late effects protocols for survivors Patient education EMPOWERS survivors
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COG Track at APHON
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Questions Acknowledgements: ♦ ♦ ♦
Paul Nathan MD Tara Henderson MD Stacey Marjerrison MD
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COG Track at APHON
Appendix 1 Summary of Late Effects Courtesy of Karla Wilson
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Examples of Potential LEs by Systems System CNS
Potential LE
Exposure
•Seizures
•Surgery
•Neuropathies
•VCR •Platinum
•Neurocognitive deficits •Leukoencephalopathy
•XRT •Surgery •IT MTX/HD-MTX/ARAC
•SMN – brain tumor •Cerebrovascular complications
•XRT
Endocrine •GH deficits
•XRT
•Hyper/hypothyroidism •Thyroid nodules/malignancy
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Examples of Potential LEs by Systems (cont) System HEENT
Potential LE •Cataracts
Exposure •XRT •Bulsulfan/Steroids
•Keratoconjunctivitis sicca (dry eyes) •XRT
Pulmonary
•Ototoxicity
•XRT •Platinum •Aminoglycosides/IVP Lasix
•Dental abnormalities
•Any chemo •XRT
•Osteoradionecrosis
•XRT > 3000 cGy
•Pulmonary fibrosis
•XRT •Bleomycin/CCNU
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Examples of Potential LEs by Systems (cont) System Cardiac GI
Potential LE
Exposure
•Cardiomyopathy
•Anthracyclines
•Valvular disease •Carotid artery disease
•XRT
Colon cancer
•XRT >3000 cGy
Esophageal strictures
•XRT •cGVHD
Fistulas/Bowel obstruction
•XRT •Surgery
Hepatitis/Hepatic toxicity
•cGVHD •6 MP/MTX •Blood products
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Examples of Potential LEs by Systems (cont) System Renal/Bladder
Reproductive
Potential LE
Exposure
•Renal toxicity
•Ifos/Platinum •Antifungal agents/Vanco •Immune suppression agents
•Bladder malignancy
•CPM
•Hemorrhagic cystitis
•CPM/Ifos
•Infertility/POF/Hypogonadism •Sexual dysfunction •Uterine insufficiency
•Alkylating agents •XRT
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Examples of Potential LEs by Systems (cont) System Musculoskeletal
Skin
Potential LE
Exposure
•AVN
•XRT
•↓BMD (Osteopenia/osteoporosis)
•Steroids/MTX •HSCT
•Kyphosis/Scoliosis •Bone malignancies •Premature epiphyseal closure •Musculoskeletal growth disorders
•XRT
•Dermatologic changes
•Busulfan/ARAC/Steroids •cGVHD
(permanent discoloration/striae)
•Permanent alopecia •Dysplastic nevi •Skin cancer
•XRT
•Scleroderma like changes
•cGHVD 66
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Examples of Potential LEs by Systems (cont) System Immune
Metabolic
Potential LE
Exposure
•Lymphoma
•HSCT
•Immune deficiency •Lymphoproliferative disorders •Chronic or life-threatening infection
•cGVHD
•Asplenism
•Surgery •XRT
•Dyslipidemia •Type II diabetes •Obesity/Overweight •Metabolic syndrome
•Chest, cranial, or abd XRT •TBI
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Examples of Potential LEs by Systems (cont) System
Potential LE
Exposure
Heme
•SMN (AML/MDS)
•Alkylating agents •HSCT
Skin, muscles, bones, soft tissues, thyroid
•Solid tumors
•Radiation
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Examples of Potential LEs by Systems (cont) System Psychosocial •Fatigue
Potential LE
Exposure •Any cancer treatment
•Chronic pain •PTSS/PTSD •Social isolation •Risky behaviors •Mental health disorders •Educational/work impediments
Other
•Secondary benign or malignant neoplasm •XRT •Alkylating agents •Infections r/t retained cuff or line tract
•Surgery
For some therapies LE risks are just based on the therapy exposure; while others (such as XRT, alkylating agents and anthracyclines) the risk for a LE is r/t cumulative dose and/or age administered.
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Abbreviations FULL TERM Abdominal Acute lymphoblastic leukemia Acute myeloid leukemia Adolescent and young adult Adrenalcorticotropic hormone Anti Mullerian Hormone Association of Pediatric Hematology/Oncology Nurses Audiogram Avascular necrosis Behavior Assessment System for Children, Second Edition Behavior Rating Inventory of Executive Function
ABBREVIATION Abd ALL AML AYA(s) ACTH AMH APHON Audio AVN BASC-2 BRIEF 70
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Abbreviations FULL TERM Bleomycin Blood-urea-nitrogen Body mass index Bone marrow density Brain tumor Calcium Carmustine Centigray Central nervous system Chemotherapy Childhood Cancer Survivorship Study
ABBREVIATION BLEO BUN BMI BMD BT Ca CCNU cGy CNS Chemo CCSS 71
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Abbreviations FULL TERM Children's Oncology Group Chimeric Chronic graft versus host disease Chronic renal failure Cisplatin Congestive heart failure Cranial radiation therapy Cranial spinal radiation therapy Creatinine Cyclophosphamide Cyclophosphamide Equivalent Dose
ABBREVIATION COG Ch cGVHD CRF CDDP CHF CRT CSRT Creat CPM CED 72
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Abbreviations FULL TERM Cytarabine Deoxyribonucleic acid Dexamethasone Doxorubicin Echocardiogram Etoposide Follicle stimulating hormone Glomerular filtration rate Granulocyte macrophage- colony stimulating factor Gray Growth hormone
ABBREVIATION ARAC DNA DEX DOXO ECHO ETOP or VP FSH GFR GMCSF or GM-CSF Gy GH 73
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Abbreviations FULL TERM Heart failure Hematopoeitic stem cell transplant Hemoglobin A1C High dose methotrexate High risk History Hodgkin lymphoma Ifosfamide Insulin-like growth factor Insulin-like growth factor 1 Intrathecal methotrexate
ABBREVIATION HF HSCT HgA1C HD-MTX HR HX HL IFOS IGF IGF-1 IT MTX 74
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Abbreviations FULL TERM Intravenous push Late effect Late Effects after High Risk Neuroblastoma Leutenizing hormone Long-Term Follow-Up Magnesium Medulloblastoma Melphalan Mercaptopurine Meter square Methotrexate
ABBREVIATION IVP LE(s) LEaHRN LH LTFU Mag MBL MELPH 6MP m2 MTX 75
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Abbreviations FULL TERM Miligram Myelodysplastic syndrome Myocardial infarction Neuroblastoma Non-Hodgkin lymphoma Oral contraceptive pill(s) Osteosarcoma Patient(s) Phosphorus Post traumatic stress disorder Post traumatic stress syndrome
ABBREVIATION mg MDS MI NBL NHL OCP(s) osteo pt(s) Phos or PO4 PTSD PTSS 76
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Abbreviations FULL TERM Posterior fossa Prednisone Premature ovarian failure Pulmonary function test Quality of Life Radiation therapy Related to Second malignant neoplasm Soft tissue sarcoma(s) Thyroid stimulating hormone Thyroxine
ABBREVIATION PF PRED POF PFT QOL XRT R/T SMN STS(s) TSH T4 77
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Abbreviations FULL TERM Topotecan Total Body Irradiation Vancomycin Versus Vinblastine Vincristine Vitamin Year(s)
ABBREVIATION TOPO TBI Vanco vs. VBL VCR Vit yr(s)
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References Ahmad SS, Reinius MA, Hatcher HM, & Ajithkumar TV. (2016). Anticancer chemotherapy in teenagers and young adults: managing long term side effects. BMJ, 7;354:i4567. Armstrong GT, Liu Q, Yasui Y, Huang S, Ness KK, Leisenring W, Hudson MM, Donaldson SS, King AA, Stovall M, Krull KR, Robison LL,& Packer RJ. (2009). Long-term outcomes among adult survivors of childhood central nervous system malignancies in the Childhood Cancer Survivor Study. J Natl Cancer Inst.,101(13):946-58. Franco VI, & Lipshultz SE. (2015). Cardiac complications in childhood cancer survivors treated with anthracyclines. Cardiol Young, 25 Suppl 2:107-16. Harake D, Franco V, Henkel JM, Miller TL, & Lipshultz SE. (2012). Cardiotoxicity in childhood cancer survivors: strategies for prevention and management. Future Cardiology, 8(4); 647-670.
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References Krull KR, Hardy KK, Kahalley LS, Schuitema I, & Kesler SR. (2018). Neurocognitive Outcomes and Interventions in Long-Term Survivors of Childhood Cancer. J Clin Oncol., 36(21):2181-2189. endocrine Levine, JM, Whitton, JA, Ginsberg, JP, Green, DM, Leisenring, WM,….Sklar, CA. (2018). Nonsurgical premature menopause and reproductive implications in survivors of childhood cancer: A report from the childhood cancer survivor study. Cancer, 124(5), 1044-1052. Meadows, AT, Friedman, DL, Neglia, JP, Donaldson, SS, Stovali, M, Hammond, S, Yasui, Y, & Inskip, P. (2009). Second neoplasms in survivors of childhood cancer: findings from the childhood cancer survivorship study cohort. JCO, 27(14); 2356-2362. 80
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References Mostoufi-Moab S, Seidel K, Leisenring WM, Armstrong GT, Oeffinger KC, Stovall M, Meacham LR, Green DM, Weathers R, Ginsberg JP, Robison LL, & Sklar CA. (2016) Endocrine Abnormalities in Aging Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study. J Clin Oncol., 34(27):3240-7. Oeffinger KC, Mertens AC, Sklar CA, Kawashima T, Hudson MM, Meadows AT, Friedman DL, Marina N, Hobbie W, Kadan-Lottick NS, Schwartz CL, Leisenring W, & Robison LL. (2006) Childhood Cancer Survivor Study. Chronic health conditions in adult survivors of childhood cancer N Engl J Med., 355(15):1572-82. Rose SR, Horne VE, Howell J, Lawson SA, Rutter MM, Trotman GE, & Corathers SD. (2016) Late endocrine effects of childhood cancer. Nat Rev Endocrinol.,(6):319-36. Turcotte LM, Neglia JP, Reulen RC, Ronckers CM, van Leeuwen FE, Morton LM, Hodgson DC, Yasui Y, Oeffinger KC, & Henderson TO. (2018) Risk, Risk Factors, and Surveillance of Subsequent Malignant Neoplasms in Survivors of Childhood Cancer: A Review. J Clin Oncol., 36(21):21452152.
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